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abstract: 'In this paper, we study the decay rate in time to solutions of the Cauchy problem for the one-dimensional viscous conservation law where the far field states are prescribed. Especially, we deal with the case that the flux function which is convex and also the viscosity is a nonlinearly degenerate one ($p$-Laplacian type viscosity). As the corresponding Riemann problem admits a Riemann solution as the constant state or the single rarefaction wave, it has already been proved by Matsumura-Nishihara that the solution to the Cauchy problem tends toward the constant state or the single rarefaction wave as the time goes to infinity. We investigate that the decay rate in time of the corresponding solutions. Furthermore, we also investigate that the decay rate in time of the solution for the higher order derivative. These are the first result concerning the asymptotic decay of the solutions to the Cauchy problem of the scalar conservation law with nonlinear viscosity. The proof is given by $L^1$, $L^2$-energy and time-weighted $L^q$-energy methods.'
address:
- 'BKC Research Organization of Social Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan /Osaka City University Advanced Mathematical Institute, Sumiyoshi, Osaka 558-8585, Japan.'
-
author:
- Natsumi Yoshida
bibliography:
- '<your-bib-database>.bib'
title: Decay properties of solutions to the Cauchy problem for the scalar conservation law with nonlinearly degenerate viscosity
---
\[thm\][Lemma]{}
viscous conservation law ,decay estimates ,asymptotic behavior ,nonlinearly degenerate viscosity ,rarefaction wave
Introduction and main theorems
==============================
In this paper, we shall consider the asymptotic behavior of solutions for the one-dimensional scalar conservation law with a nonlinearly degenerate viscosity ($p$-Laplacian type viscosity with $p>1$) $$\begin{aligned}
\left\{\begin{array}{ll}
\partial_tu +\partial_x \bigl(f(u) \bigr)
= \mu \,
\partial_x \left( \,
\left| \, \partial_xu \, \right|^{p-1} \partial_xu \,
\right)
\qquad &(t>0, x\in \mathbb{R}), \\[5pt]
u(0,x) = u_0(x) \qquad &( x \in \mathbb{R} ),\\[5pt]
\displaystyle{\lim_{x\to \pm \infty}} u(t,x) =u_{\pm}
\qquad &\bigl( t \ge 0 \bigr).
\end{array}
\right.\,\end{aligned}$$ Here, $u=u(t,x)$ denotes the unknown function of $t>0$ and $x\in \mathbb{R}$, the so-called conserved quantity, $f=f(u)$ is the flux function depending only on $u$, $\mu$ is the viscosity coefficient, $u_0$ is the given initial data, and constants $u_{\pm } \in \mathbb{R}$ are the prescribed far field states. We suppose the given flux $f=f(u)$ is a $C^3$-function satisfying $f(0)=f'(0)=0$, $\mu$ is a positive constant and far field states $u_{\pm }$ satisfy $u_-<u_+$ without loss of generality.
At first, we shall motivate the physical meaning to the nonlinearly degenerate viscosity and review the related models conscerning with the Cauchy problem (1.1). It is known that if $p=1$ and $f(u)=\frac{1}{2} u^2$, the equation in our problem (1.1) becomes the viscous Burgers equation: $$\partial_tu +u \, \partial_x u
= \mu \,
\partial_x^2 u.$$ In particular, the viscosity term $\mu \, \partial_x^2 u$ stands for Newtonian fluid. The Newtonian fluid is what satisfies the relation between the strain rate $\partial_{x_{j}} u_{i} + \partial_{x_{i}} u_{j}$ ($\partial_x u$, for one-dimensional case) is linear, that is, $$\tau = \mu \left( \, \partial_{x_{j}} u_{i} + \partial_{x_{i}} u_{j} \, \right)
\quad {\rm{or}} \quad \tau = \mu \, \partial_x u.$$ On the other hand, if a fluid satisfies the relation between the strain rate and the stress is nonlinear (for example, polymers, viscoelastic or viscoplastic flow), the fluid is non-Newtonian fluid, such as, blood, honey, butter, whipped cream, suspension, and so on. The typical nonlinearity in the non-Newtonian fluid is the power-law fluid (cf. [@ma-pr-st]), that is, $$\tau = \mu \left( \, \partial_{x_{j}} u_{i} + \partial_{x_{i}} u_{j} \, \right)^p
\quad {\rm{or}} \quad \tau = \mu \left( \, \partial_x u \, \right)^p.$$ Lady[ž]{}enskaja [@lad1] has proposed a new mathematical model for the imcompressible Navier-Stokes equation with the power-law type nonlinear viscosity (see also [@du-gu]). The Lady[ž]{}enskaja equation is the following: $$\partial_tu_{i} + u_{j} \, \partial_{x_{j}} u_{i}
= - \partial_{x_{i}} p +
\partial_{x_{j}} \left( \, \Biggl( \,
\mu_{0} + \mu_{1} \biggl( \,
\sum_{\substack{i,j \\ }} \left( \, \partial_{x_{i}} u_{j} \, \right)^2
\, \biggr)^{\frac{r}{2}}
\, \Biggr) \partial_{x_{j}} u_{i} \, \right)
+ f_{i}$$ where $i=1,2$, or $i=1,2,3$. In particular, if $\mu_{0}=0,\mu_{1}>0$ and $r>-1$, this model is said to be the Ostwald-de Waele model: $$\partial_tu_{i} + u_{j} \, \partial_{x_{j}} u_{i}
= - \partial_{x_{i}} p +
\partial_{x_{j}} \biggl( \, \Bigl( \,
\mu \, \left| \, D \vec{u} \, \right|^{r}
\, \Bigr) \partial_{x_{j}} u_{i} \, \biggr)
+ f_{i}$$ where $\left| \, D \vec{u} \, \right|
:=\biggl( \,
\displaystyle{\sum_{\substack{i,j \\ }}}
\left( \, \partial_{x_{i}} u_{j} \, \right)^2
\, \biggr)^{\frac{1}{2}}$, and $i=1,2$, or $i=1,2,3$. In this sence, our viscosity $\mu \,
\partial_x \left( \,
\left| \, \partial_xu \, \right|^{p-1} \partial_xu \,
\right)$ should be called the Ostwald-de Waele type viscosity.
We are interested in the asymptotic behavior and its precise estimates in time of the global solution to our problem (1.1). It can be expected that the large-time behavior is closely related to the weak solution (“Riemann solution”) of the corresponding Riemann problem (cf. [@lax], [@smoller]) for the non-viscous hyperbolic part of (1.1): $$\begin{aligned}
\left\{\begin{array} {ll}
\partial _t u + \partial _x \bigl( f(u) \bigr)=0
\qquad &(t>0, x\in \mathbb{R}),\\[5pt]
u(0,x)=u_0 ^{\rm{R}} (x)\qquad &(x \in \mathbb{R}),
\end{array}
\right.\,\end{aligned}$$ where $u_0 ^{\rm{R}}$ is the Riemann data defined by $$u_0 ^{\rm{R}} (x)=u_0 ^{\rm{R}} (x\: ;\: u_- ,u_+)
:=
\left\{\begin{array} {ll}
u_- & \; (x < 0),\\[5pt]
u_+ & \; (x > 0).
\end{array}\right.$$ In fact, for $p=1$ in (1.1), the usual linear viscosity case: $$\begin{aligned}
\left\{\begin{array}{ll}
\partial_tu +\partial_x \bigl(f(u) \bigr)= \mu \, \partial_x^2 u
\qquad &(t>0, x\in \mathbb{R}), \\[5pt]
u(0,x) = u_0(x) \qquad &( x \in \mathbb{R} ),\\[5pt]
\displaystyle{\lim_{x\to \pm \infty}} u(t,x) =u_{\pm}
\qquad &\bigl( t \ge 0 \bigr),
\end{array}
\right.\,\end{aligned}$$ when the smooth flux function $f$ is genuinely nonlinear on the whole space $\mathbb{R}$, i.e., $f''(u)\ne 0\ (u\in \mathbb{R})$, Il’in-Ole[ĭ]{}nik [@ilin-oleinik] showed the following: if $f''(u) > 0\ (u\in \mathbb{R})$, that is, the Riemann solution consists of a single rarefaction wave solution, the global solution in time of the Cauchy problem (1.3) tends toward the rarefaction wave; if $f''(u) < 0\ (u\in \mathbb{R})$, that is, the Riemann solution consists of a single shock wave solution, the global solution of the Cauchy problem (1.3) does the corresponding smooth traveling wave solution (“viscous shock wave”) of (1.3) with a spacial shift (cf. [@ilin-kalashnikov-oleinik]). Hattori-Nishihara [@hattori-nishihara] also proved that the asymptotic decay rate in time, of the solution toward the single rarefaction wave, is $(1+t)^{-{\frac{1}{2}}\, \left(1-\frac{1}{p} \right)}$ in the $L^p$-norm $\bigl(1\leq p\leq \infty \bigr)$ for large $t>0$ (see also [@hashimoto-kawashima-ueda], [@hashimoto-matsumura], [@nakamura]). More generally, in the case of the flux functions which are not uniformly genuinely nonlinear, when the Riemann solution consists of a single shock wave satisfying Ole[ĭ]{}nik’s shock condition, Matsumura-Nishihara [@matsu-nishi3] showed the asymptotic stability of the corresponding viscous shock wave. Moreover, Matsumura-Yoshida [@matsumura-yoshida] considered the circumstances where the Riemann solution generically forms a pattern of multiple nonlinear waves which consists of rarefaction waves and waves of contact discontinuity (refer to [@liep-rosh]), and investigated that the case where the flux function $f$ is smooth and genuinely nonlinear (that is, $f$ is convex function or concave function) on the whole $\mathbb{R}$ except a finite interval $I := (a,b) \subset \mathbb{R}$, and linearly degenerate on $I$, that is, $$\left\{
\begin{array}{ll}
f''(u) >0 & \; \bigl(u \in (-\infty ,a\, ]\cup [\, b,+\infty )\bigr),\\[5pt]
f''(u) =0 & \; \bigl(u \in (a,b)\bigr).
\end{array}\right.$$ Under the conditions (1.4), they proved the unique global solution in time to the Cauchy problem (1.3) tends uniformly in space toward the multiwave pattern of the combination of the viscous contact wave and the rarefaction waves as the time goes to infinity. Yoshida [@yoshida] also obtained that the precise decay properties for the asymptotics toward the multiwave pattern. In fact, owing to [@yoshida], the decay rate in time is $(1+t)^{-{\frac{1}{2}}\, \left(\frac{1}{2}-\frac{1}{p} \right)}$ in the $L^p$-norm $\bigl(2\leq p<+\infty \bigr)$ and $(1+t)^{-{\frac{1}{4}}\, +\epsilon}$ for any $\epsilon >0$ in the $L^\infty$-norm if the initial perturbation from the corresponding asymptotics satisfies $H^1$. Furthermore, if the perturbation satisfies $H^1\cap L^1$, the decay rate in time is $(1+t)^{-{\frac{1}{2}}\, \left(1-\frac{1}{p} \right)\, +\epsilon }$ for any $\epsilon >0$ in the $L^p$-norm $\bigl(1\leq p<+\infty \bigr)$ and $(1+t)^{-{\frac{1}{2}}\, +\epsilon}$ for any $\epsilon >0$ in the $L^\infty$-norm.
For $p>1$, there are few results for the asymptotic behavior for the problem (1.1) (the related problems are studied in [@gur-mac], [@nagai-mimura1], [@nagai-mimura2] and so on). In the case where the flux function is genuinely nonlinear on the whole space $\mathbb{R}$, Matsumura-Nishihara [@matsu-nishi3] proved that if the far field states satisfy $u_- = u_+=:\tilde{u}$, then the solution tends toward the constant state $\tilde{u}$, and if the far field states $u_- < u_+$, then the solution tends toward a single rarefaction wave. In the case where the flux function satisfies (1.4), Yoshida [@yoshida'] recently showed that the asymptotics which tends toward the multiwave pattern of the combination of the viscous contact wave constructed by the Barenblatt-Kompanceec-Zel’dovi[č]{} solution (see also [@carillo-toscani], [@huang-pan-wang], [@kamin]) of the porous medium equation, and the rarefaction waves. However, the decay rate of any asymptotics of the problem (1.1) has been not known.
The aim of the present paper is to obtain the precise time-decay estimates for the asympotics of the previous study in [@matsu-nishi2].
[**Stability Theorem 1.1**]{} (Matsumura-Nishihara [@matsu-nishi2])[**.**]{}
[**Stability Theorem 1.2**]{} (Matsumura-Nishihara [@matsu-nishi2])[**.**]{}
Now we are ready to state our main results.
[**Theorem 1.1**]{} (Main Theorem I)[**.**]{}
[**Theorem 1.2**]{} (Main Theorem II)[**.**]{}
[**Theorem 1.3**]{} (Main Theorem III)[**.**]{}
[**Theorem 1.4**]{} (Main Theorem IV)[**.**]{}
[**Theorem 1.5**]{} (Main Theorem V)[**.**]{}
[**Theorem 1.6**]{} (Main Theorem VI )[**.**]{}
This paper is organized as follows. In Section 2, we shall prepare the basic properties of the rarefaction wave. In Section 3, we reformulate the problem in terms of the deviation from the asymptotic state (similarly in [@matsumura-yoshida], [@yoshida], [@yoshida']), that is, the single rarefaction wave. Following the arguments in [@matsu-nishi2], we also prepare some uniform boundedness and energy estimates of the deviation as the solution to the reformulated problem. In order to obtain the time-decay estimates (Theorem 1.4 and Theorem 1.5), in Section 4 and Section 5, we establish the uniform energy estimates in time by using a very technical time-weighted energy method. In Section 6, we prove the time-decay $L^{r+1}$-estimate for the higher order derivative, Theorem 1.6. We shall finally discuss the time-decay rates in our main theorems comparing with those for a Cauchy problem of the symplest $p$-Laplacian evolution equation without convective term in Section 7.
[**Some Notation.**]{} We denote by $C$ generic positive constants unless they need to be distinguished. In particular, use $C(\alpha, \beta, \cdots )$ or $C_{\alpha, \beta, \cdots }$ when we emphasize the dependency on $\alpha, \beta, \cdots $. Use $\mathbb{R}^{+}$ as $
\mathbb{R}^{+}:=(0,\infty),
$ and the symbol “$\vee $” as $$a\vee b:= \max \{a,b\}.$$ We also use the Friedrichs mollifier $\rho_\delta \ast $, where, $\rho_\delta(x):=\frac{1}{\delta}\rho \left( \frac{x}{\delta}\right)$ with $$\begin{aligned}
\begin{aligned}
&\rho \in C^{\infty}_0(\mathbb{R}),\quad
\rho (x)\geq 0\: (x \in \mathbb{R}), \\
&\mathrm{supp} \{\rho \} \subset
\left\{x \in \mathbb{R}\: \left|\: |\, x \, |\le 1 \right. \right\},\quad
\int ^{\infty}_{-\infty} \rho (x)\, \mathrm{d}x=1,
\end{aligned}\end{aligned}$$ and $\rho_\delta \ast f$ denote the convolution. For function spaces, $L^p = L^p(\mathbb{R})$ and $H^k = H^k(\mathbb{R})$ denote the usual Lebesgue space and $k$-th order Sobolev space on the whole space $\mathbb{R}$ with norms $||\cdot||_{L^p}$ and $||\cdot||_{H^k}$, respectively. We also define the bounded $C^{m}$-class $\mathscr{B}^{m}$ as follows $$f\in \mathscr{B}^{m}(\Omega)
\, \Longleftrightarrow \,
f\in C^m(\Omega),
\;
\sup _{\Omega}\, \sum _{k=0}^{m} \, \bigl| \, D^kf\, \bigr|<\infty$$ for $m< \infty$ and $$f\in \mathscr{B}^{\infty }(\Omega)
\, \Longleftrightarrow \,
\forall n\in \mathbb{N},\, f\in C^n(\Omega),
\;
\sup _{\Omega}\, \sum _{k=0}^{n} \, \bigl| \, D^kf\, \bigr|<\infty$$ where $\Omega \subset \mathbb{R}^d$ and $D^k$ denote the all of $k$-th order derivatives.
Preliminaries
=============
In this section, we shall arrange the two lemmas concerned with the basic properties of the rarefaction wave for accomplishing the proof of our main theorems. Since the rarefaction wave $u^r$ is not smooth enough, we need some smooth approximated one as in the previous results in [@hashimoto-matsumura], [@liu-matsumura-nishihara], [@matsu-nishi1], [@matsumura-yoshida]. We start with the well-known arguments on $u^r$ and the method of constructing its smooth approximation. We first consider the rarefaction wave solution $w^r$ to the Riemann problem for the non-viscous Burgers equation $$\label{riemann-burgers}
\left\{\begin{array}{l}
\partial _t w +
\displaystyle{ \partial _x \left( \, \frac{1}{2} \, w^2 \right) } = 0
\, \, \; \; \qquad \quad \qquad ( t > 0,\,x\in \mathbb{R}),\\[7pt]
w(0,x) = w_0 ^{\rm{R}} ( \, x\: ;\: w_- ,w_+):= \left\{\begin{array}{ll}
w_+ & \, \: \; \quad (x>0),\\[5pt]
w_- & \, \: \; \quad (x<0),
\end{array}
\right.
\end{array}
\right.$$ where $w_\pm \in \mathbb{R} \: (w_-<w_+)$ are the prescribed far field states. The unique global weak solution $w=w^r\left( \, \frac{x}{t}\: ;\: w_-,w_+\right)$ of (\[riemann-burgers\]) is explicitly given by $$\label{rarefaction-burgers}
w^r \left( \, \frac{x}{t}\: ;\: w_-,w_+\right) :=
\left\{\begin{array}{ll}
w_{-} & \bigl(\, x \leq w_{-}t \, \bigr),\\[5pt]
\displaystyle{ \frac{x}{t} } & \bigl(\, w_{-} t \leq x \leq w_{+} t \, \bigr),\\[5pt]
w_+ & \bigl(\, x\geq w_{+} t \, \bigr).
\end{array}\right.$$ Next, under the condition $f''(u)>0\ (u\in \mathbb{R})$ and $u_-<u_+$, the rarefaction wave solution $u=u^r\left( \, \frac{x}{t}\: ;\: u_-,u_+\right)$ of the Riemann problem (1.2) for hyperbolic conservation law is exactly given by $$u^r\left( \, \frac{x}{t} \: ; \: u_-,u_+\right)
= (\lambda)^{-1}\biggl( w^r\left( \, \frac{x}{t} \: ; \: \lambda_-,\lambda_+\right)\biggr)$$ which is nothing but (1.6), where $\lambda_\pm := \lambda(u_\pm) = f'(u_\pm)$. We define a smooth approximation of $w^r(\, \frac{x}{t}\: ;\: w_-,w_+)$ by the unique classical solution $$w=w(\, t,x\: ;\: w_-,w_+)\in \mathscr{B}^{\infty }( \, [\, 0,\infty )\times \mathbb{R})$$ to the Cauchy problem for the following non-viscous Burgers equation $$\begin{aligned}
\label{smoothappm}
\left\{\begin{array}{l}
\partial _t w
+ \displaystyle{ \partial _x \left( \, \frac{1}{2} \, w^2 \right) } =0
\, \, \; \; \quad \qquad \qquad \qquad \qquad \qquad
(\ t>0,\,x\in \mathbb{R}),\\[7pt]
w(0,x)
= w_0(x)
:= \displaystyle{ \frac{w_-+w_+}{2} + \frac{w_+-w_-}{2}\tanh x }
\qquad \quad \; \: (x\in \mathbb{R}),
\end{array}
\right.\end{aligned}$$ By using the method of characteristics, we get the following formula $$\begin{aligned}
\left\{\begin{array} {l}
w(t,x)=w_0\bigl(x_0(t,x)\bigr)=
\displaystyle{ \frac{\lambda_-+\lambda_+}{2} }
+ \displaystyle{ \frac{\lambda_+-\lambda_-}{2}\tanh \bigl( x_0(t,x) \bigr)} ,\\[7pt]
x=x_0(t,x)+w_0\bigl(x_0(t,x)\bigr)\,t.
\end{array}
\right.\,\end{aligned}$$ We also note the assumption of the flux function $f$ to be $\lambda'(u)\left( =\frac{\mathrm{d}^2f}{\mathrm{d}u^2}(u)\right)>0$. Now we summarize the results for the smooth approximation $w(\, t,x\: ;\: w_-,w_+)$ in the next lemma. Since the proof is given by the direct calculation as in [@matsu-nishi1], we omit it.
[**Lemma 2.1.**]{}
We define the approximation for the rarefaction wave $u^r\left( \, \frac{x}{t}\: ;\: u_-,u_+\right)$ by $$U^r(\, t,x\: ; \: u_-,u_+) := (\lambda)^{-1} \bigl( w(\, t,x\: ;\: \lambda_-,\lambda_+)\bigr).$$
Then we have the next lemma as in the previous works (cf. [@hashimoto-matsumura], [@liu-matsumura-nishihara], [@matsu-nishi1], [@matsumura-yoshida]).
[**Lemma 2.2.**]{}
Because the proofs of (1) to (4) are given in [@matsu-nishi1], (5) to (7) are in [@matsumura-yoshida] and (8) is in [@yoshida], we omit the proofs here.
Reformulation of the problem
============================
In this section, we reformulate our Cauchy problem (1.1) in terms of the deviation from the asymptotic state, the single rarefaction wave. We first should note by Lemma 2.2, the asymptotic state $u^r\left( \, \frac{x}{t}\: ;\: u_-,u_+\right)$ can be replaced by $$U^r( t,x \: ; \: u_-, u_+).$$ In fact, from Lemma 2.1 (especially (8)), it follows that for any $\epsilon>0$ $$\begin{aligned}
\begin{aligned}
&\left|\left| \,
U^r( t,\cdot \: ; \: u_-, u_+)
- u^r\left( \, \frac{\cdot}{t}\: ;\: u_-,u_+\right)\,
\right|\right|_{L^q}\\
&\le C_{\epsilon,q}(1+t)^{-\left( 1-\frac{1}{q}\right)+\epsilon}
\qquad (t\ge 0\, ;\, 1\le q\le \infty).
\end{aligned}\end{aligned}$$ Then it is noted that $U^r$ is monotonically increasing and approximately satisfies the equation of (1.1) as $$\partial _tU^r +\partial_x \bigl(f(U^r)\bigr)= 0.$$ Now putting $$u(t,x) = U^r(t,x) + \phi(t,x)$$ and using (3.1), we can reformulate the problem (1.1) in terms of the deviation $\phi $ from $U^r$ as $$\begin{aligned}
\left\{\begin{array}{ll}
\partial _t\phi + \partial_x \left( f(U^r+\phi) - f(U^r) \right) \\[5pt]
- \mu \, \partial_x
\left( \,
\bigl| \, \partial_x U^r + \partial_x \phi \, \bigr|^{p-1}
\bigl( \, \partial_x U^r + \partial_x \phi \, \bigr) -
\bigl| \, \partial_x U^r \, \bigr|^{p-1} \partial_x U^r \,
\right)\\[2pt]
\, \: \; \quad \quad \qquad \qquad
= \mu \,
\partial_x \left( \,
\bigl| \, \partial_x U^r \, \bigr|^{p-1} \partial_x U^r
\, \right)
\, \, \, \: \: \quad (t>0, x\in \mathbb{R}), \\[5pt]
\phi(0,x) = \phi_0(x)
:= u_0(x)-U^r(0,x)
\qquad \qquad \quad \; \: \: \; \; \: \; \; \,\, \, \, (x\in \mathbb{R}).
\end{array}
\right.\,\end{aligned}$$ Then we look for the global solution in time $$\phi \in C^0\bigl( \, [\, 0,\infty)\, ;L^2 \bigr)
\cap L^{\infty}\bigl( \, \mathbb{R}^{+} \, ;L^{2} \bigr)$$ with $$\partial _x \phi \in L^{\infty} \bigl( \, \mathbb{R}^{+} \, ;L^{p+1} \bigr)
\cap L^{p+1}
\bigl(\, {\mathbb{R}^{+}_{t}}
\times {\mathbb{R}}_{x} \bigr).$$ Here we note that the assumptions on $u_0$ and the fact $
\partial_x U^r(0,\cdot \, )\in L^{p+1}
$ imply $\phi_0 \in L^2$ with $\partial _x \phi_0 \in L^{p+1}$. Then the corresponding our main theorems for $\phi$ we should prove are as follows.
[**Theorem 3.1.**]{}
[**Theorem 3.2.**]{}
[**Theorem 3.3.**]{}
In order to accomplish the proofs of Theorem 3.1, Theorem 3.2 and Theorem 3.3, we will need some estimates about boundedness of the perturbation $\phi$ and $u$. We shall arrange some lemmas for them.
By using the maximum principle (cf. [@ilin-kalashnikov-oleinik], [@ilin-oleinik]), we first have the following uniform boundedness of the perturbation $\phi$ (and also $u$), that is,
[**Lemma 3.1**]{} (uniform boundedness)[**.**]{}
Secondly, we also have the uniform estimates of $\phi$ as follows (for the proof of it, see [@matsu-nishi2] ).
[**Lemma 3.2**]{} (uniform estimates)[**.**]{}
Time-decay estimates with $2 \le q \le \infty$
===============================================
In this section, we show the time-decay estimates with $2 \le q \le \infty$ (not assuming $L^1$-integrability to the initial perturbation), that is, Theorem 3.1. To do that, we shall obtain the time-weighted $L^q$-energy estimates to $\phi$ with $2 \le q< \infty$ (cf. [@yoshida]).
[**Proposition 4.1.**]{}
The proof of Proposition 4.1 is provided by the following two lemmas.
[**Lemma 4.1.**]{}
[**Lemma 4.2.**]{}
In what follows, we first prove Lemma 4.1 and Lemma 4.2, and finally give the proof of Proposition 4.1.
[**Proof of Lemma 4.1**]{}. Multiplying the equation in (3.3) by $\left|\phi \right|^{q-2} \phi$ with $2\leq q < \infty$, we obtain the divergence form $$\begin{aligned}
\begin{aligned}
&\partial_t\left(\frac{1}{q} \left|\, \phi \, \right|^q \right)
+\partial _x
\biggl( \,
\left|\, \phi \, \right|^{q-2} \phi \,
\bigl( f(U^r+\phi)-f(U^r) \bigr)
\biggr) \\
&+\partial _x \left(
-(q-1)\int _0^{\phi}
\bigl( f(U^r+\eta)-f(U^r) \bigr)\left|
\, \eta \, \right|^{q-2}
\, \mathrm{d}\eta
\, \right) \\
&+\partial _x \biggl( \,
-\mu \, \left|\, \phi \, \right|^{q-2} \phi \,
\biggr.\\
& \quad \times \biggl.
\Bigl( \,
\bigl|\, \partial _x U^r + \partial _x \phi \, \bigr|^{p-1}
\bigl( \, \partial _x U^r + \partial _x \phi \, \bigr)
- \bigl|\, \partial _x U^r \, \bigr|^{p-1}
\bigl( \, \partial _x U^r \, \bigr) \,
\Bigr)
\, \biggr) \\
&+(q-1)\int _0^{\phi}
\bigl( \lambda(U^r+\eta)-\lambda(U^r) \bigr)\left|
\, \eta \, \right|^{q-2}
\, \mathrm{d}\eta \, \bigl( \, \partial _x U^r \, \bigr) \\
&+\mu \, (q-1) \, \left|\, \phi \, \right|^{q-2} \partial _x \phi \, \\
& \quad \times
\Bigl( \,
\bigl|\, \partial _x U^r + \partial _x \phi \, \bigr|^{p-1}
\bigl( \, \partial _x U^r + \partial _x \phi \, \bigr)
- \bigl|\, \partial _x U^r \, \bigr|^{p-1}
\bigl( \, \partial _x U^r \, \bigr) \,
\Bigr)\\
&=\mu \, \left|\, \phi \, \right|^{q-2} \phi \,
\partial _x
\bigl( \, \bigl| \partial _x U^r \bigr|^{p-1}
\partial _x U^r \, \bigr). \end{aligned}
\end{aligned}$$ Integrating (4.3) with respect to $x$, we have $$\begin{aligned}
\begin{aligned}
&\frac{1}{q} \frac{\mathrm{d}}{\mathrm{d}t}
\,\Vert \, \phi(t) \, \Vert_{L^q}^q \\
&+\int ^{\infty }_{-\infty } (q-1) \int _0^{\phi}
\left( \lambda(U^r+\eta)-\lambda(U^r) \right)\left|
\, \eta \, \right|^{q-2}
\, \mathrm{d}\eta \, \bigl( \, \partial _x U^r \, \bigr)
\, \mathrm{d}x \\
&+\mu \, (q-1) \, \int ^{\infty }_{-\infty }
\left|\, \phi \, \right|^{q-2} \partial _x \phi \, \\
& \quad \times
\Bigl( \,
\bigl|\, \partial _x U^r + \partial _x \phi \, \bigr|^{p-1}
\bigl( \, \partial _x U^r + \partial _x \phi \, \bigr)
- \bigl|\, \partial _x U^r \, \bigr|^{p-1}
\bigl( \, \partial _x U^r \, \bigr) \,
\Bigr)
\, \mathrm{d}x \\
&= \mu
\int ^{\infty}_{-\infty} \left|\, \phi \, \right|^{q-2} \phi
\, \partial _x
\bigl( \, \bigl| \partial _x U^r \bigr|^{p-1}
\partial _x U^r \, \bigr) \, \mathrm{d}x.
\end{aligned}
\end{aligned}$$ By using the uniform boundedness, Lemma 3.1, and the following absolute equality with $p>1$, for any $a,b \in \mathbb{R}$, $$\begin{aligned}
\begin{aligned}
&\left(\, |\, a\, |^{p-1}a - |\, b\, |^{p-1}b \, \right)
\left(\, a-b \, \right) \\
&= \frac{1}{2} \,
\left(\, |\, a\, |^{p-1} + |\, b\, |^{p-1} \, \right)
\left(\, a-b \, \right)^2
+ \frac{1}{2} \,
\left(\, |\, a\, |^{p-1} - |\, b\, |^{p-1} \, \right)
\left(\, a^2-b^2 \, \right),
\end{aligned}\end{aligned}$$ we have $$\begin{aligned}
\begin{aligned}
&\frac{1}{q} \frac{\mathrm{d}}{\mathrm{d}t}
\,\Vert \, \phi(t) \, \Vert_{L^q}^q
+ (q-1) \,
\left( \,
\displaystyle{\min _{|u| \leq \widetilde{C}} {\lambda}'(u)} \,
\right) \,
\int ^{\infty }_{-\infty }
\left|\, \phi \, \right|^{q}
\, \partial _x U^r
\, \mathrm{d}x \\
&+\frac{\mu \, (q-1)}{2} \,
\int ^{\infty }_{-\infty }
| \, \phi \, |^{q-2}
\bigl( \, \partial _x \phi \, \bigr)^2
\left( \,
\bigl| \partial _x \phi + \partial _x U^r \bigr|^{p-1} + \bigl| \partial _x U^r \bigr|^{p-1}
\, \right)
\, \mathrm{d}x \\
&+\frac{\mu \, (q-1)}{2} \,
\int ^{\infty }_{-\infty }
| \, \phi \, |^{q-2} \,
\left| \,
\bigl| \partial _x \phi + \partial _x U^r \bigr|^{p-1}
- \bigl| \partial _x U^r \bigr|^{p-1}
\, \right| \\
& \qquad \qquad \qquad \qquad \quad \; \; \, \,
\times
\left| \,
\bigl( \, \partial _x \phi + \partial _x U^r \, \bigr)^2
- \bigl( \, \partial _x U^r \, \bigr)^2 \, \right|
\, \mathrm{d}x \\
&\leq \mu \, \left| \,
\int ^{\infty}_{-\infty} \left|\, \phi \, \right|^{q-2} \phi
\, \partial _x
\bigl( \, \bigl| \partial _x U^r \bigr|^{p-1}
\partial _x U^r \, \bigr) \, \mathrm{d}x
\, \right|.
\end{aligned}
\end{aligned}$$ Thus, multiplying the inequality by $(1+t)^{\alpha}$ with $\alpha>0$ and integrating over $(0,t)$ with respect to the time, we complete the proof of Lemma 4.1.
[**Proof of Lemma 4.2**]{}. Noting that $\phi (t, \cdot \: ) \in L^2$ and $\partial_x \phi (t, \cdot \: ) \in L^{p+1}$ imply $\displaystyle{\lim _{x\rightarrow \pm \infty}\phi(t,x)}=0$ for $t \ge 0$, we have $$\begin{aligned}
\begin{aligned}
| \, \phi \, |^{s}
&\leq s \int _{-\infty}^{\infty}
| \, \phi \, |^{s-1} \,
\bigl| \, \partial _x \phi \, \bigr|
\, \mathrm{d}x.\\ \end{aligned}\end{aligned}$$ By the Cauchy-Schwarz inequality, we have $$\begin{aligned}
\begin{aligned}
| \, \phi \, |^{s}
&\leq s \left( \,
\int _{-\infty}^{\infty}
\left( \, | \, \phi \, |^{s-1-\frac{q-2}{p+1}} \, \right)^{\frac{p+1}{p}}
\, \mathrm{d}x
\right)^{\frac{p}{p+1}} \\
& \qquad \times
\left( \,
\int _{-\infty}^{\infty}
| \, \phi \, |^{q-2}
\bigl| \, \partial _x \phi \, \bigr|^{p+1}
\, \mathrm{d}x
\right)^{\frac{1}{p+1}}. \end{aligned}\end{aligned}$$ Taking $s=\frac{3p+q-1}{p+1}$, we get $$\begin{aligned}
\begin{aligned}
\Vert \, \phi \, \Vert _{L^\infty }^{\frac{3p+q-1}{p+1}}
&\le \frac{3\, p+q-1}{p+1}
\left( \,
\int _{-\infty}^{\infty}
| \, \phi \, |^{2}
\, \mathrm{d}x
\, \right)^{\frac{p}{p+1}} \\
& \qquad \times
\left( \,
\int _{-\infty}^{\infty}
| \, \phi \, |^{q-2}
\bigl| \, \partial _x \phi \, \bigr|^{p+1}
\, \mathrm{d}x
\right)^{\frac{1}{p+1}},
\end{aligned}\end{aligned}$$ and $$\begin{aligned}
\begin{aligned}
\Vert \, \phi \, \Vert _{L^r }^r
&\le \Vert \, \phi \, \Vert _{L^\infty }^{r-2}
\Vert \, \phi \, \Vert _{L^2 }^2\\
&\le \left( \frac{3\, p+q-1}{p+1} \right)^{\frac{(p+1)(r-2)}{3p+q-1}}
\left( \,
\int _{-\infty}^{\infty}
| \, \phi \, |^{2}
\, \mathrm{d}x
\, \right)^{\frac{pr+p+q-1}{3p+q-1}} \\
& \qquad \times
\left( \,
\int _{-\infty}^{\infty}
| \, \phi \, |^{q-2}
\bigl| \, \partial _x \phi \, \bigr|^{p+1}
\, \mathrm{d}x
\right)^{\frac{r-2}{3p+q-1}}.
\end{aligned}\end{aligned}$$ Thus, we complete the proof of Lemma 4.2.
[**Proof of Proposition 4.1**]{}.By using Lemma 4.1 and Lemma 4.2, we shall estimate the second term, the third term and the fourth term on the right-hand side of (4.2) as follows: for any $\epsilon>0$, $$\begin{aligned}
\begin{aligned}
&\alpha \int ^t_0 (1+\tau )^{\alpha -1}
\| \,\phi(\tau) \,\|_{L^q}^q
\, \mathrm{d}\tau \\
&\le C_{\alpha ,p,q} \int ^t_0 (1+\tau )^{\alpha -1}
\left( \,
\int _{-\infty}^{\infty}
| \, \phi \, |^{q-2}
\bigl| \, \partial _x \phi \, \bigr|^{p+1}
\, \mathrm{d}x
\right)^{\frac{q-2}{3p+q-1}} \\
&\qquad \qquad \qquad \qquad \qquad \quad \times
\left( \,
\int _{-\infty}^{\infty}
| \, \phi \, |^{2}
\, \mathrm{d}x
\, \right)^{\frac{pq+p+q-1}{3p+q-1}}
\, \mathrm{d}\tau \\
&\le \int ^t_0
\left( \,
(1+\tau )^{\alpha}
\int _{-\infty}^{\infty}
| \, \phi \, |^{q-2}
\bigl| \, \partial _x \phi \, \bigr|^{p+1}
\, \mathrm{d}x
\, \right)^{\frac{q-2}{3p+q-1}} \\
&\qquad \quad \quad \quad \quad \times
C_{\alpha ,p,q}\, (1+\tau )^{\alpha - 1 -\frac{\alpha (q-2)}{3p+q-1}}
\| \,\phi(\tau) \,\|_{L^2}^{\frac{2(pq+p+q-1)}{3p+q-1}}
\, \mathrm{d}\tau \\
&\le \epsilon \int ^t_0 (1+\tau )^{\alpha}
\left( \,
\int _{-\infty}^{\infty}
| \, \phi \, |^{q-2}
\bigl| \, \partial _x \phi \, \bigr|^{p+1}
\, \mathrm{d}x
\right) \, \mathrm{d}\tau \\
&\quad \quad \quad \quad \quad
+C_{\alpha ,p,q}(\epsilon )
\int ^t_0 (1+\tau )^{\alpha - {\frac{3p+q-1}{3p+1}}}
\| \,\phi(\tau ) \,\|_{L^2}^{\frac{2(pq+p+q-1)}{3p+1}}
\, \mathrm{d}\tau,
\end{aligned}\end{aligned}$$ $$\begin{aligned}
\begin{aligned}
&q \int ^t_0 (1+\tau )^{\alpha}
\| \,\phi(\tau ) \,\|_{L^\infty}^{q-1}
\left| \,
\int ^{\infty}_{-\infty} \left|\, \phi \, \right|^{q-2} \phi
\, \partial _x
\bigl( \, \bigl| \partial _x U^r \bigr|^{p-1}
\partial _x U^r \, \bigr) \, \mathrm{d}x
\, \right|
\, \mathrm{d}\tau \\
&\le C_{p,q} \int ^t_0 (1+\tau )^{\alpha}
\left( \,
\int _{-\infty}^{\infty}
| \, \phi \, |^{q-1}
\bigl| \, \partial _x \phi \, \bigr|^{p+1}
\, \mathrm{d}x
\right)^{\frac{q-1}{3p+q-1}} \\
&\qquad \quad \quad \times
\left( \,
\int _{-\infty}^{\infty}
| \, \phi \, |^{2}
\, \mathrm{d}x
\, \right)^{\frac{p(q-1)}{3p+q-1}}
\left|\left| \,
\partial _x
\bigl( \, \bigl| \partial _x U^r \bigr|^{p-1}
\partial _x U^r \, \bigr)(\tau )
\, \right| \right|_{L^1}
\, \mathrm{d}\tau \\
&\le \int ^t_0
\left( \,
(1+\tau )^{\alpha}
\int _{-\infty}^{\infty}
| \, \phi \, |^{q-2}
\bigl| \, \partial _x \phi \, \bigr|^{p+1}
\, \mathrm{d}x
\, \right)^{\frac{q-2}{3p+q-1}} \\
&\quad \: \: \: \times
C_{p,q}\, (1+\tau )^{\alpha -\frac{\alpha (q-1)}{3p+q-1}}
\| \,\phi(\tau) \,\|_{L^2}^{\frac{2p(q-1)}{3p+q-1}}
\left|\left| \,
\partial _x
\bigl( \, \bigl| \partial _x U^r \bigr|^{p-1}
\partial _x U^r
\, \bigr)(\tau ) \, \right| \right|_{L^1}
\, \mathrm{d}\tau \\
&\le \epsilon \int ^t_0 (1+\tau )^{\alpha}
\left( \,
\int _{-\infty}^{\infty}
| \, \phi \, |^{q-1}
\bigl| \, \partial _x \phi \, \bigr|^{p+1}
\, \mathrm{d}x
\right)
\, \mathrm{d}\tau \\
&\quad
+ C_{p,q}(\epsilon) \int ^t_0
(1+\tau )^{\alpha} \| \,\phi(\tau ) \,\|
_{L^2}^{{\frac{2}{3}}(q-1)}
\left|\left| \,
\partial _x
\bigl( \, \bigl| \partial _x U^r \bigr|^{p-1}
\partial _x U^r \, \bigr)(\tau ) \, \right| \right|_{L^1}
^{\frac{3p+q-1}{3p}}
\, \mathrm{d}\tau.
\end{aligned}\end{aligned}$$ Substituting (4.11) and (4.12) into (4.2), we have $$\begin{aligned}
\begin{aligned}
&(1+t)^\alpha \| \,\phi(t) \,\|_{L^q}^q
+ \int ^t_0 (1+\tau )^\alpha \int _{-\infty}^{\infty}
| \, \phi \, |^{q} \, \partial _x U^r
\, \mathrm{d}x \mathrm{d}\tau \\
& + \int ^t_0 (1+\tau )^\alpha \int _{-\infty}^{\infty}
| \, \phi \, |^{q-2}
\bigl( \, \partial _x \phi \, \bigr)^2
\left( \,
\bigl| \partial _x \phi \bigr|^{p-1}
+ \bigl| \partial _x U^r \bigr|^{p-1}
\, \right) \, \mathrm{d}x \mathrm{d}\tau \\
& + \int ^t_0 (1+\tau )^\alpha \int _{-\infty}^{\infty}
| \, \phi \, |^{q-2} \,
\left| \,
\bigl| \partial _x \phi + \partial _x U^r \bigr|^{p-1}
- \bigl| \partial _x U^r \bigr|^{p-1}
\, \right| \\
& \qquad \qquad \qquad \qquad \quad \quad \; \, \,
\times
\left| \,
\bigl( \, \partial _x \phi + \partial _x U^r \, \bigr)^2
- \bigl( \, \partial _x U^r \, \bigr)^2 \, \right|
\, \mathrm{d}x \mathrm{d}\tau \\
&\leq C_{\alpha,p,q} \| \,\phi_0 \,\|_{L^q}^q
+ C_{\alpha,p,q}
\int ^t_0 (1+\tau )^{\alpha - {\frac{3p+q-1}{3p+1}}}
\| \,\phi(\tau ) \,\|_{L^2}^{\frac{2(pq+p+q-1)}{3p+1}}
\, \mathrm{d}\tau \\
& \qquad \qquad \qquad \quad \:
+ C_{p,q}
\int ^t_0
(1+\tau )^{\alpha} \| \,\phi(\tau ) \,\|
_{L^2}^{{\frac{2}{3}}(q-1)} \\
& \qquad \qquad \qquad \qquad \quad \quad \times
\left|\left| \,
\partial _x
\bigl( \, \bigl| \partial _x U^r \bigr|^{p-1}
\partial _x U^r \, \bigr)(\tau ) \, \right| \right|_{L^1}
^{\frac{3p+q-1}{3p}}
\, \mathrm{d}\tau.
\end{aligned}\end{aligned}$$ By using the $L^2$-boundedness of $\phi$, (3.6), and $$\begin{aligned}
\begin{aligned}
\left|\left| \,
\partial _x
\bigl( \, \bigl| \partial _x U^r \bigr|^{p-1}
\partial _x U^r \, \bigr)(\tau ) \, \right| \right|_{L^1}
& \leq p \, \| \, \partial _x U^r (t) \,\|_{L^{\infty}}^{p-1}
\| \, \partial _x^2 U^r (t) \,\|_{L^1} \\
& \leq C_{p} (1+t)^{-p},
\end{aligned}\end{aligned}$$ we estimate the each terms on the right-hand side of (4.13) as follows: $$\begin{aligned}
\begin{aligned}
&C_{\alpha ,p,q} \,
\int ^t_0 (1+\tau )^{\alpha - {\frac{3p+q-1}{3p+1}}}
\| \,\phi(\tau ) \,\|_{L^2}^{\frac{2(pq+p+q-1)}{3p+1}}
\, \mathrm{d}\tau \\
&\leq C_{\alpha ,p,q}
\bigl( \, C_{p}(\phi_0) \, \bigr)^{\frac{pq+p+q-1}{3p+1}}
\int ^t_0 (1+\tau )^{\alpha - {\frac{3p+q-1}{3p+1}}}
\, \mathrm{d}\tau \\
&\leq C_{\alpha ,p,q}
\bigl( \, C_{p}(\phi_0) \, \bigr)^{\frac{pq+p+q-1}{3p+1}}
(1+t )^{\alpha - {\frac{q-2}{3p+1}}},
\end{aligned}\end{aligned}$$ $$\begin{aligned}
\begin{aligned}
&C_{p,q} \int ^t_0
(1+\tau )^{\alpha} \| \,\phi(\tau ) \,\|
_{L^2}^{{\frac{2}{3}}(q-1)}
\left|\left| \,
\partial _x
\bigl( \, \bigl| \partial _x U^r \bigr|^{p-1}
\partial _x U^r \, \bigr)(\tau ) \, \right| \right|_{L^1}
^{\frac{3p+q-1}{3p}}
\, \mathrm{d}\tau \\
&\leq C_{p,q}
\bigl( \, C_{p}(\phi_0) \, \bigr)^{{\frac{1}{3}}(q-1)}
\int ^t_0 (1+\tau )^{\alpha - {\frac{3p+q-1}{3}} }
\, \mathrm{d}\tau \\
&\leq C_{p,q}
\bigl( \, C_{p}(\phi_0) \, \bigr)^{{\frac{1}{3}}(q-1)}
(1+t )^{\alpha - {\frac{3p+q-4}{3}}}.
\end{aligned}\end{aligned}$$ Substituting (4.15) and (4.16) into (4.13), we get (4.1). Thus the proof of Proposition 4.1 is complete. In particular, it follows that $$\begin{aligned}
\begin{aligned}
\| \,\phi(t) \,\|_{L^q}
\leq C( \, p, \,q, \, \phi_0 \, ) \,
(1+t)^{-{\frac{1}{3p+1}} \left( 1 - {\frac{2}{q}} \right)}
\end{aligned}\end{aligned}$$ for $2 \leq q < \infty$.
[**Proof of Theorem 3.1.**]{} We already have proved the decay estimate of $\| \,\phi(t) \,\|_{L^q}$ with $2 \le q < \infty$. Therefore we only show the $L^{\infty}$-estimate. We first note by Lemma 2.2 that $$\begin{aligned}
\begin{aligned}
&\bigl|\bigl|
\, \partial _x \phi (t)\,
\bigr|\bigr| _{L^{p+1}}^{p+1}\\
&\leq \bigl|\bigl|
\, \partial _x u (t)\,
\bigr|\bigr| _{L^{p+1}}^{p+1}
+ \bigl|\bigl|
\, \partial _x U^r (t)\,
\bigr|\bigr| _{L^{p+1}}^{p+1} \\
&\leq C\bigl( \, \| \, \phi_0 \, \|_{L^2}, \:
\| \, \partial _x u_0 \, \|_{L^{p+1}}
\, \bigr)
+ C_{p}(1+t)^{-p}.
\end{aligned}\end{aligned}$$ We use the following Gagliardo-Nirenberg inequality: $$\begin{aligned}
\| \,\phi(t) \,\|_{L^\infty }
\le C_{q,\theta}
\| \,\phi(t) \,\|_{L^q}^{1-\theta}
\| \,\partial _x \phi(t) \,\|_{L^{p+1}}^{\theta}\end{aligned}$$ for any $(q,\theta)\in [\, 1,\infty)\times (0,1\, ]$ satisfying $$\frac{p}{p+1} \, {\theta}=(1-\theta) \, \frac{1}{q}.$$ Substituting (4.17) and (4.18) into (4.19), we have $$\begin{aligned}
\begin{aligned}
\| \,\phi(t) \,\|_{L^\infty }
&\le C( \, p, \,q, \, \theta, \, \phi_0, \, \partial _x u_0 \, ) \,
(1+t)^{-{\frac{1}{3p+1}} \left( 1 - {\frac{2}{q}} \right)(1-\theta)}\\
&\le C( \, p, \, \theta, \, \phi_0, \, \partial _x u_0 \, ) \,
(1+t)^{-{\frac{1}{3p+1}} + {\frac{\theta}{p+1}}}
\end{aligned}\end{aligned}$$ for $\theta \in (0,1\, ]$. Consequently, we do complete the proof of Theorem 3.1.
Time-decay estimates with $1 \le q \le \infty$
===============================================
In this section, we show the time-decay estimates with $1 \le q \le \infty$ and time-decay estimate for the higher order derivative in the $L^{p+1}$-norm, in the case where $\phi_0 \in L^1 \cap L^2$ with $\partial _x u_0 \in L^{p+1}$, that is, Theorem 3.2. Then, we first establish the $L^1$-estimate to the solution $\phi$ of the reformulated Cauchy problem (3.3). To do that, we use the Friedrichs mollifier $\rho_\delta \ast $, where, $\rho_\delta(\phi):=\frac{1}{\delta}\rho \left( \frac{\phi}{\delta}\right)$ with $$\begin{aligned}
\begin{aligned}
&\rho \in C^{\infty}_0(\mathbb{R}), \quad
\rho (\phi)\geq 0 \quad (\phi \in \mathbb{R}),
\\
&\mathrm{supp} \{\rho \} \subset
\left\{\phi \in \mathbb{R}\: \left|\: |\,\phi \, |\le 1 \right. \right\},\quad
\int ^{\infty}_{-\infty} \rho (\phi)\, \mathrm{d}\phi=1.
\end{aligned}\end{aligned}$$
Some useful properties of the mollifier are as follows.
[**Lemma 5.1.**]{}
Making use of Lemma 5.1, we obtain the following $L^1$-estimate.
[**Proposition 5.1.**]{}
[**Proof of Proposition 5.1.**]{}Multiplying the equation in the problem (3.3) by $\left( \rho_\delta \ast \mathrm{sgn} \right)(\phi)$, we obtain the divergence form $$\begin{aligned}
\begin{aligned}
&\partial_t\left(
\int^{\phi}_0
\left( \rho_\delta \ast \mathrm{sgn} \right)(\eta)
\, \mathrm{d}\eta
\right) \\
&+\partial _x
\biggl( \,
\left( \rho_\delta \ast \mathrm{sgn} \right)(\phi) \,
\bigl( f(U^r+\phi)-f(U^r) \bigr)
\biggr) \\
&+\partial _x \left(
-\int _0^{\phi}
\bigl( f(U^r+\eta)-f(U^r) \bigr)
\frac{\mathrm{d}\left( \rho_\delta \ast \mathrm{sgn} \right)}
{\mathrm{d}\phi}
(\eta)
\, \mathrm{d}\eta
\, \right) \\
&+\partial _x \biggl( \,
-\mu \, \left( \rho_\delta \ast \mathrm{sgn} \right)(\phi) \biggr. \\
& \quad \times \biggl.
\Bigl( \,
\bigl|\, \partial _x U^r + \partial _x \phi \, \bigr|^{p-1}
\bigl( \, \partial _x U^r + \partial _x \phi \, \bigr)
- \bigl|\, \partial _x U^r \, \bigr|^{p-1}
\bigl( \, \partial _x U^r \, \bigr) \,
\Bigr)
\, \biggr) \\
&+\int _0^{\phi}
\bigl( \lambda(U^r+\eta)-\lambda(U^r) \bigr)
\frac{\mathrm{d}\left( \rho_\delta \ast \mathrm{sgn} \right)}
{\mathrm{d}\phi}(\eta)
\, \mathrm{d}\eta \, \bigl( \, \partial _x U^r \, \bigr) \\
&+\mu \,
\frac{\mathrm{d}\left( \rho_\delta \ast \mathrm{sgn} \right)}
{\mathrm{d}\phi}(\phi) \,
\partial _x \phi \\
& \quad \times
\Bigl( \,
\bigl|\, \partial _x U^r + \partial _x \phi \, \bigr|^{p-1}
\bigl( \, \partial _x U^r + \partial _x \phi \, \bigr)
- \bigl|\, \partial _x U^r \, \bigr|^{p-1}
\bigl( \, \partial _x U^r \, \bigr) \,
\Bigr) \\
& =\mu \,
\left( \rho_\delta \ast \mathrm{sgn} \right)(\phi) \,
\partial _x
\bigl( \, \bigl| \partial _x U^r \bigr|^{p-1}
\partial _x U^r \, \bigr).
\end{aligned}\end{aligned}$$ By using (4.5) and integrating (5.2) with respect to $x$ and $t$, we have $$\begin{aligned}
\begin{aligned}
&\int ^{\infty}_{-\infty} \int^{\phi (t) }_0
\left( \rho_\delta \ast \mathrm{sgn} \right)(\eta)
\, \mathrm{d}\eta \, \mathrm{d}x \\
&+ \int _0^t \int ^{\infty}_{-\infty} \int^{\phi}_0
\bigl( \lambda(U^r+\eta)-\lambda(U^r) \bigr)
\frac{\mathrm{d}\left( \rho_\delta \ast \mathrm{sgn} \right)}
{\mathrm{d}\phi}(\eta)
\, \mathrm{d}\eta \, \bigl( \, \partial _x U^r \, \bigr)
\, \mathrm{d}x \mathrm{d}\tau \\
&+ \frac{\mu}{2} \int _0^t \int ^{\infty}_{-\infty}
\frac{\mathrm{d}\left( \rho_\delta \ast \mathrm{sgn} \right)}
{\mathrm{d}\phi}(\phi) \,
\bigl( \, \partial _x \phi \, \bigr)^2
\left( \,
\bigl| \partial _x \phi + \partial _x U^r \bigr|^{p-1} + \bigl| \partial _x U^r \bigr|^{p-1}
\, \right)
\, \mathrm{d}x \mathrm{d}\tau \\
&+ \frac{\mu}{2} \int _0^t \int ^{\infty}_{-\infty}
\frac{\mathrm{d}\left( \rho_\delta \ast \mathrm{sgn} \right)}
{\mathrm{d}\phi}(\phi) \,
\left| \,
\bigl| \partial _x \phi + \partial _x U^r \bigr|^{p-1}
- \bigl| \partial _x U^r \bigr|^{p-1}
\, \right| \\
& \qquad \qquad \qquad \qquad \quad \quad \quad \; \, \,
\times
\left| \,
\bigl( \, \partial _x \phi + \partial _x U^r \, \bigr)^2
- \bigl( \, \partial _x U^r \, \bigr)^2 \, \right|
\, \mathrm{d}x \mathrm{d}\tau \\
&= \int ^{\infty}_{-\infty} \int^{\phi _0}_0
\left( \rho_\delta \ast \mathrm{sgn} \right)(\eta)
\, \mathrm{d}\phi \, \mathrm{d}x \\
&\qquad \qquad \qquad \;
+ \mu
\int _0^t \int ^{\infty}_{-\infty}
\left( \rho_\delta \ast \mathrm{sgn} \right)(\phi) \,
\partial _x
\bigl( \, \bigl| \partial _x U^r \bigr|^{p-1}
\partial _x U^r \, \bigr)
\, \mathrm{d}x \mathrm{d}\tau .
\end{aligned}\end{aligned}$$ By using Lemma 5.1, we note that for $t\in [\, 0,\infty)$, $$\begin{aligned}
\begin{aligned}
& \int ^{\infty}_{-\infty} \int^{\phi (t)}_0
\bigl( \lambda(U^r+\eta)-\lambda(U^r) \bigr)
\frac{\mathrm{d}\left( \rho_\delta \ast \mathrm{sgn} \right)}
{\mathrm{d}\phi}(\eta)
\, \mathrm{d}\eta \, \bigl( \, \partial _x U^r \, \bigr)
\, \mathrm{d}x \\
& \ge 2 \,
\left( \,
\displaystyle{\min _{|u| \leq \widetilde{C}} {\lambda}'(u)} \,
\right) \,
\int ^{\infty }_{-\infty }
\left|\,
\int^{| \phi (t) |}_0
\eta \, \rho_\delta (\eta )
\mathrm{d}\eta
\, \right|
\, \bigl( \, \partial _x U^r \, \bigr)
\, \mathrm{d}x
\ge 0,
\end{aligned}\end{aligned}$$ $$\begin{aligned}
\left| \,
\int^{\phi}_0\left( \rho_\delta \ast \mathrm{sgn} \right)(\eta)
\, \mathrm{d}\eta
\, \right|
\le \left( \rho_\delta \ast \mathrm{sgn} \right)
(|\, \phi \,|)\, |\, \phi \,|
\le |\, \phi \,|, \end{aligned}$$ $$\begin{aligned}
\displaystyle {\lim_{\delta\rightarrow 0}}
\int ^{\infty}_{-\infty} \int^{\phi (t) }_0
\left( \rho_\delta \ast \mathrm{sgn} \right)(\eta)
\, \mathrm{d}\eta
= \| \,\phi(t) \,\|_{L^1}, \end{aligned}$$ and we get $$\begin{aligned}
\begin{aligned}
&\| \,\phi (t) \,\|_{L^1}
\le \| \,\phi_0 \,\|_{L^1} \\
&\qquad \quad
+ \displaystyle {\mu \, \lim_{\delta\rightarrow 0}}
\int^t_0 \left|\, \int ^{\infty}_{-\infty}
\left( \rho_\delta \ast \mathrm{sgn} \right)(\phi) \,
\partial _x
\bigl( \, \bigl| \partial _x U^r \bigr|^{p-1}
\partial _x U^r \, \bigr)
\, \mathrm{d}x \, \right|\, \mathrm{d}\tau.
\end{aligned}\end{aligned}$$ By using (4.14), we can also get $$\begin{aligned}
\begin{aligned}
& \displaystyle {\lim_{\delta\rightarrow 0}}
\left|\, \int ^{\infty}_{-\infty}
\left( \rho_\delta \ast \mathrm{sgn} \right)(\phi) \,
\partial _x
\bigl( \, \bigl| \partial _x U^r \bigr|^{p-1}
\partial _x U^r \, \bigr)
\, \mathrm{d}x \, \right|\, (t) \\
& \leq \left(\, \int ^{\infty}_{-\infty}
\bigl| \, \mathrm{sgn} (\phi) \, \bigr| \,
\Bigl| \,
\partial _x
\bigl( \, \bigl| \partial _x U^r \bigr|^{p-1}
\partial _x U^r \, \bigr)
\, \Bigr|
\, \mathrm{d}x \, \right)\, (t) \\
& \leq C_{p}(1+t)^{-p}
\quad \bigl( t \ge 0 \bigr).
\end{aligned}\end{aligned}$$ Then, substituting (5.8) into (5.7), we have the desired $L^1$-estimate (5.1).
Next, we show the time-weighted $L^q$-energy estimates to $\phi$.
[**Proposition 5.2.**]{}
The proof of Proposition 5.2 is given by the following two lemmas.
[**Lemma 5.2.**]{}
[**Lemma 5.3.**]{}
The proofs of Lemma 5.2, Lemma 5.3 and Proposition 5.2 are given in the same way as those of Lemma 4.1, Lemma 4.2 and Proposition 4.1, so we omit them. We particularly note that we have by Proposition 5.2 $$\| \,\phi (t) \,\|_{L^q}
\leq C( \, p, \, q, \, \phi_0 \, )\, (1+t)^
{-\frac{1}{2p}\left( 1- \frac{1}{q} \right)}$$ for $1\leq q < \infty$.
We shall finally obtain the time-decay estimates for the higher order derivatives, that is, $\partial _x \phi$ and $\partial _x u$, and also get the $L^{\infty}$-estimate for $\phi$.
[**Proposition 5.3.**]{}
To obtain Proposition 5.3, we first show the following.
[**Lemma 5.4.**]{}
[**Proof of Lemma 5.4.**]{}Multiplying the equation in the problem (1.1), that is, $$\partial_tu +\partial_x \bigl(f(u) \bigr)
= \mu \,
\partial_x \left( \,
\left| \, \partial_xu \, \right|^{p-1} \partial_xu \,
\right)$$ by $$- \partial_x \left( \,
\left| \, \partial_xu \, \right|^{p-1} \partial_xu \,
\right),$$ we obtain the divergence form $$\begin{aligned}
\begin{aligned}
&\partial_t
\left(\frac{1}{p+1} \left|\, \partial _x u \, \right|^{p+1} \right)
+ \partial _x \Bigl( \,
- \, \left|\, \partial _x u \, \right|^{p-1}
\partial _x u \cdot \partial _t u \, \Bigr) \\
&\qquad \; \,
+ \partial _x \left(
- \, \frac{p}{p+1} \,
f'(u) \left|\, \partial _x u \, \right|^{p+1}
\, \right) \\
&\qquad \; \, + \frac{p}{p+1} \,
f''(u) \left|\, \partial _x u \, \right|^{p+1}\partial _x u
+\mu \, p\, q \left|\, \partial _x u \, \right|^{2(p-1)}
\bigl( \, \partial _x^2 u \, \bigr)^2
= 0.
\end{aligned}\end{aligned}$$ Integrating the divergence form (5.14) with respect to $x$, we have $$\begin{aligned}
\begin{aligned}
&\frac{1}{p+1} \,
\frac{\mathrm{d}}{\mathrm{d}t}\,
\,\Vert \, \partial _x u (t) \, \Vert_{L^{p+1}}^{p+1}
+\mu \, p^2 \int ^{\infty }_{-\infty }
\left|\, \partial _x u \, \right|^{2(p-1)}
\bigl( \, \partial _x^2 u \, \bigr)^2
\, \mathrm{d}x \\
&\qquad \qquad \qquad \qquad \quad \; \; \; \:
+\frac{p}{p+1} \int ^{\infty }_{-\infty }
f''(u) \left|\, \partial _x u \, \right|^{p+1}\partial _x u
\, \mathrm{d}x
= 0.
\end{aligned}\end{aligned}$$ We separate the integral region to the third term on the left-hand side of (5.15) as $$\begin{aligned}
\begin{aligned}
&\int ^{\infty }_{-\infty }
f''(u) \left|\, \partial _x u \, \right|^{p+1}\partial _x u
\, \mathrm{d}x \\
&= \int _{\partial _x u \geq 0 } + \int _{\partial _x u < 0 } \\
&= \int _{\partial _x u \geq 0 }
f''(u) \left|\, \partial _x u \, \right|^{p+2} \, \mathrm{d}x
- \int _{\partial _x u < 0 }
f''(u) \left|\, \partial _x u \, \right|^{p+2} \, \mathrm{d}x.
\end{aligned}\end{aligned}$$ Substituting (5.16) into (5.15), we get the following equality $$\begin{aligned}
\begin{aligned}
&\frac{1}{p+1} \,
\frac{\mathrm{d}}{\mathrm{d}t}\,
\,\Vert \, \partial _x u (t) \, \Vert_{L^{p+1}}^{p+1}
+\mu \, p^2 \int ^{\infty }_{-\infty }
\left|\, \partial _x u \, \right|^{2(p-1)}
\bigl( \, \partial _x^2 u \, \bigr)^2
\, \mathrm{d}x \\
& \; \: \, +\frac{p}{p+1} \int _{\partial _x u \geq 0 }
f''(u) \left|\, \partial _x u \, \right|^{p+2} \, \mathrm{d}x
= \frac{p}{p+1} \int _{\partial _x u < 0 }
f''(u) \left|\, \partial _x u \, \right|^{p+2} \, \mathrm{d}x.
\end{aligned}\end{aligned}$$ Multiplying (5.17) by $(1+t)^{\alpha}$ with $\alpha>0$ and integrating over $(0,t)$ with respect to the time, we complete the proof of Lemma 5.4.
[**Proof of Proposition 5.3.**]{}We use the following important results (cf. [@yoshida']).
[**Lemma 5.5.**]{}
In fact, taking care of the relation by using Lemma 2.2 $$\begin{aligned}
\begin{aligned}
\partial _x u = \partial _x U^r + \partial _x \phi <0 \,
\Longleftrightarrow \, \partial _x \phi <0,
\, \partial _x U^r < \bigl|\, \partial _x \phi \, \bigr|,
\end{aligned}\end{aligned}$$ we immediately have $$\begin{aligned}
\begin{aligned}
\int _{\partial _x u < 0 }
&f''(u) \left|\, \partial _x u \, \right|^{s} \, \mathrm{d}x \\
&\leq 2^{s} \,
\left( \, \max_{ | u | \leq \widetilde{C}} f''(u) \, \right)
\int _{\partial _x \phi < 0, \partial _x U^r < | \partial _x \phi | }
\left|\, \partial _x \phi \, \right|^{s} \, \mathrm{d}x.
\end{aligned}\end{aligned}$$
Since $ \partial _x u $ is absolutely continuous, we first note that for any $
x \in \bigl\{ \, x \in \mathbb{R} \, \, \bigr.
\bigl| \, \partial _x u \, < \, 0 \, \bigr\},
$ there exsists $
x_{k} \in \mathbb{R}\cup \{ - \infty \}
$ such that $$\partial _x u (x_{k}) = 0, \; \;
\partial _x u (y) \, < \, 0 \;
\bigl( \, y \in
( x_{k},x ) \, \bigr).$$ Therefore, it follows that for such $x$ and $x_{k}$ with $q\geq p\, (\, >1\, )$, $$\begin{aligned}
\left|\, \partial _x u \, \right|^q
= \left(\, - \partial _x u \, \right)^q
= q \int_{x_k}^{x}
\left(\, - \partial _x u \, \right)^{q-1} \left(\, - \partial _x^2 u \, \right)
\, \mathrm{d}y \end{aligned}$$ By using the Cauchy-Schwarz inequality, we have
[**Lemma 5.6.**]{} By using Young’s inequality to (5.22), we also have
[**Lemma 5.7.**]{} By using Lemma 5.5, Lemma 5.6 and Lemma 5.7 with $\epsilon = \frac{\mu \, p^2 \, (p+1)}{2}$, we have $$\begin{aligned}
\begin{aligned}
&(1+t)^\alpha
\| \, \partial _x u (t)\, \| _{L^{p+1}}^{p+1} \\
& \quad
+ \frac{\mu \, p^2 \, (p+1)}{2}
\int ^t_0 (1+\tau )^\alpha \int _{-\infty}^{\infty}
\bigl| \, \partial _x u \, \bigr|^{2(p-1)}
\left( \, \partial _x^2 u \, \right)^2
\, \mathrm{d}x \mathrm{d}\tau \\
& \qquad \quad \quad \; \; \; \: \,
+ p \int ^t_0 (1+\tau )^\alpha
\int _{\partial _x u \geq 0}
f''(u) \left|\, \partial _x u \, \right|^{p+1}
\, \mathrm{d}x \mathrm{d}\tau \\
&\leq \| \, \partial _x u_{0} \, \| _{L^{p+1}}^{p+1} \\ & \quad
+ \alpha \int ^t_0 (1+\tau )^{\alpha -1}
\Bigl( \,
\| \, \partial _x \phi (\tau) \, \| _{L^{p+1}}^{p+1}
+ \| \, \partial _x U^r (\tau) \, \| _{L^{p+1}}^{p+1}
\, \Bigr)
\, \mathrm{d}\tau \\
& \quad
+ C_{p} \int ^t_0 (1+\tau )^\alpha
\left( \,
\int _{\partial _x u < 0 }
\left|\, \partial _x u \, \right|^{p+1}
\, \mathrm{d}x \,
\right)^{\frac{2}{3p}+1} \mathrm{d}\tau .
\end{aligned}\end{aligned}$$ By using Proposition 5.2, we get the following time-decay estimates.
[**Lemma 5.8.**]{}
By using Lemma 5.8 with $\alpha \mapsto \alpha - 1 \gg 1$ and $q=2$, we have $$\begin{aligned}
\alpha \int ^t_0 (1+\tau )^{\alpha - 1}
\| \, \partial _x \phi (\tau) \, \| _{L^{p+1}}^{p+1}
\, \mathrm{d}\tau
\leq C\left( \, \alpha, \, p, \, \phi_0 \, \right) \,
(1+t)^{\alpha - \frac{2p+1}{2p}}. \end{aligned}$$ We can also estimate by using Lemma 2.2 as $$\begin{aligned}
\alpha \int ^t_0 (1+\tau )^{\alpha - 1}
\| \, \partial _x U^r (\tau) \, \| _{L^{p+1}}^{p+1}
\, \mathrm{d}\tau
\leq C\left( \, \alpha, \, p \, \right) \,
(1+t)^{\alpha - p}. \end{aligned}$$ By using the uniform boundedness in Lemma 3.2, that is, $$\| \, \partial _x u (t)
\, \| _{L^{p+1}}^{p+1}
\leq
C_{p}\bigl(\, \| \, \phi _0 \, \| _{L^2},
\| \, \partial _x u_0 \, \| _{L^{p+1}} \, \bigr)$$ and Lemma 5.8 with $q=2$, we can estimate as $$\begin{aligned}
\begin{aligned}
&C_{p} \int ^t_0 (1+\tau )^\alpha
\left( \,
\int _{\partial _x u < 0 }
\left|\, \partial _x u \, \right|^{p+1}
\, \mathrm{d}x \,
\right)^{\frac{2}{3p}+1} \mathrm{d}\tau \\
&\leq C_{p} \int ^t_0 (1+\tau )^\alpha
\int _{\partial _x u < 0 }
\left|\, \partial _x \phi \, \right|^{p+1}
\, \mathrm{d}x
\cdot
\| \, \partial _x u (\tau) \, \| _{L^{p+1}}^{\frac{2(p+1)}{3p}}
\, \mathrm{d}\tau \\
&\leq C\left( \, p, \, \phi_0, \, \partial _x u_0 \, \right) \,
\int ^t_0 (1+\tau )^\alpha
\int _{-\infty}^{\infty}
\left|\, \partial _x \phi \, \right|^{p+1}
\, \mathrm{d}x \mathrm{d}\tau \\
&\leq C\left( \, \alpha, \, p, \, \phi_0, \, \partial _x u_0 \, \right) \, (1+t)^{\alpha - \frac{1}{2p}}.
\end{aligned}\end{aligned}$$ Substituting (5.26), (5.27) and (5.28) into (5.24), we complete the proof of Proposition 5.3. In particular, we have $$\begin{aligned}
\| \, \partial _x u (t) \, \| _{L^{p+1}}^{p+1}
\, \mathrm{d}\tau
\leq C\left( \, p, \, \phi_0, \, \partial _x u_0 \, \right) \,
(1+t)^{- \frac{1}{2p}}, \end{aligned}$$ and $$\begin{aligned}
\begin{aligned}
\| \, \partial _x \phi (t) \, \| _{L^{p+1}}^{p+1}
\, \mathrm{d}\tau
& \leq \| \, \partial _x u (t) \, \| _{L^{p+1}}^{p+1}
+ \| \, \partial _x U^r (t) \, \| _{L^{p+1}}^{p+1} \\
& \leq C\left( \, p, \, \phi_0, \, \partial _x u_0 \, \right) \,
(1+t)^{- \frac{1}{2p}}
\end{aligned}\end{aligned}$$ for $1 \leq q < \infty$.
[**Proof of Theorem 3.2.**]{} We already have proved the decay estimate of $\| \,\phi(t) \,\|_{L^q}$ with $1 \le q < \infty$. Therefore we only show the following time-decay estimate for the higher order derivative $$\begin{aligned}
\begin{aligned}
&\bigl|\bigl|\,
\partial _x u(t) \,
\bigr|\bigr|_{L^{p+1} }, \, \; \;
\left|\left|\,
\partial _x \phi (t)
\,\right|\right|_{L^{p+1} } \\[5pt]
& \leq \left\{\begin{array} {ll}
C( \, \epsilon, \, p, \, \phi_0, \, \partial _x u_0 \, ) \,
(1+t)^{-\frac{p}{p+1}}\\[15pt]
\, \, \, \: \; \; \quad \qquad
\left( \, 1 < p \le
\displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{(p+1)(3p-2)}{3}\, \epsilon } }
\, \right),\\[15pt]
C( \, \epsilon, \, p, \, \phi_0, \, \partial _x u_0 \, ) \,
(1+t)^{-\frac{3}{2(p+1)(3p-2)} + \epsilon}\\[15pt]
\, \, \, \; \; \quad \qquad \qquad
\left( \,
\displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{(p+1)(3p-2)}{3}\, \epsilon } }
< p \, \right)
\end{array}
\right.\,
\end{aligned}\end{aligned}$$ for any $0<\epsilon \ll 1$, and the $L^{\infty}$-estimate for $\phi$.
We first prove (5.31). Substituting (5.29) into (5.28), we have $$\begin{aligned}
\begin{aligned}
&C_{p} \int ^t_0 (1+\tau )^\alpha
\int _{\partial _x u < 0 }
\left|\, \partial _x \phi \, \right|^{p+1}
\, \mathrm{d}x
\cdot
\| \, \partial _x u (\tau) \, \| _{L^{p+1}}^{\frac{2(p+1)}{3p}}
\, \mathrm{d}\tau \\
&\leq C\left( \, p, \, \phi_0, \, \partial _x u_0 \, \right) \,
\int ^t_0 (1+\tau )
^{\alpha - \frac{1}{2p} \cdot \frac{2}{3p}}
\int _{-\infty}^{\infty}
\left|\, \partial _x \phi \, \right|^{p+1}
\, \mathrm{d}x \mathrm{d}\tau.
\end{aligned}\end{aligned}$$
By using Lemma 5.8 with $\alpha \mapsto \alpha - \frac{1}{2p} \cdot \frac{2}{3p} \gg 1$ and $q=2$, we also have $$\begin{aligned}
\alpha \int ^t_0 (1+\tau )^{\alpha - 1}
\| \, \partial _x \phi (\tau) \, \| _{L^{p+1}}^{p+1}
\, \mathrm{d}\tau
\leq C\left( \, \alpha, \, p, \, \phi_0 \, \right) \,
(1+t)^{\alpha - \frac{1}{2p} \cdot \frac{2}{3p} - \frac{1}{2p}}. \end{aligned}$$ Substituting (5.33) into (5.24), we have $$\begin{aligned}
\begin{aligned}
&\bigl|\bigl|\,
\partial _x u(t) \,
\bigr|\bigr|_{L^{p+1} }^{p+1}, \, \; \;
\left|\left|\,
\partial _x \phi (t)
\,\right|\right|_{L^{p+1} }^{p+1} \\[5pt] & \leq C( \, p, \, \phi_0, \, \partial _x u_0 \, ) \\
& \quad \times
\left( \,
(1+t)^{-\frac{2p+1}{2p}} + (1+t)^{-p}
+ (1+t)
^{-\left( \frac{1}{2p} \cdot \frac{2}{3p} + \frac{1}{2p} \right)}
\, \right) \\[5pt]
& \leq \left\{\begin{array} {ll}
C( \, p, \, \phi_0, \, \partial _x u_0 \, ) \,
\left( \,
(1+t)^{-p}
+ (1+t)
^{-\left( \frac{1}{2p} \cdot \frac{2}{3p} + \frac{1}{2p} \right)}
\, \right) \\[15pt]
\, \: \: \; \; \quad \qquad \qquad \qquad \qquad \qquad \qquad \,
\left( \, 1 < p \le \displaystyle{\frac{1 + \sqrt{3}}{2}} \, \right),\\[15pt]
C( \, p, \, \phi_0, \, \partial _x u_0 \, ) \,
\left( \,
(1+t)^{-\frac{2p+1}{2p}}
+ (1+t)
^{-\left( \frac{1}{2p} \cdot \frac{2}{3p} + \frac{1}{2p} \right)}
\, \right) \\[15pt]
\, \: \: \; \; \quad \qquad \qquad \qquad \qquad \qquad \qquad \qquad
\left( \, \displaystyle{\frac{1 + \sqrt{3}}{2}} < p \, \right).
\end{array}
\right.\,
\end{aligned}\end{aligned}$$ Iterating “$\infty$”-times the above process, we will get $$\begin{aligned}
\begin{aligned}
&\bigl|\bigl|\,
\partial _x u(t) \,
\bigr|\bigr|_{L^{p+1} }^{p+1}, \, \; \;
\left|\left|\,
\partial _x \phi (t)
\,\right|\right|_{L^{p+1} }^{p+1} \\[5pt]
& \leq \left\{\begin{array} {ll}
C( \, \epsilon, \, p, \, \phi_0, \, \partial _x u_0 \, ) \,
\left( \,
(1+t)^{-p}
+ (1+t)
^{- \mathlarger{ \frac{1}{2p}}
\substack{{\infty }\\{\substack{{{\mathlarger{\sum}}}\\{n=0}}}}
\mathlarger{\left( \frac{2}{3p} \right)^{n} + \epsilon} }
\, \right) \\[15pt]
\quad \quad \quad \; \: \, \,
\, \: \: \; \; \quad \qquad \qquad \qquad \qquad \qquad \qquad \,
\left( \, 1 < p \le \displaystyle{\frac{1 + \sqrt{3}}{2}} \, \right),\\[15pt]
C( \, \epsilon, \, p, \, \phi_0, \, \partial _x u_0 \, ) \,
\left( \,
(1+t)^{-\frac{2p+1}{2p}}
+ (1+t)
^{- \mathlarger{ \frac{1}{2p}}
\substack{{\infty }\\{\substack{{{\mathlarger{\sum}}}\\{n=0}}}}
\mathlarger{\left( \frac{2}{3p} \right)^{n}+ \epsilon} }
\, \right) \\[15pt]
\quad \quad \quad \; \: \, \,
\, \: \: \; \; \quad \qquad \qquad \qquad \qquad \qquad \qquad \qquad
\left( \, \displaystyle{\frac{1 + \sqrt{3}}{2}} < p \, \right),
\end{array}
\right.\, \\[15pt]
& \leq \left\{\begin{array} {ll}
C( \, \epsilon, \, p, \, \phi_0, \, \partial _x u_0 \, ) \,
\left( \,
(1+t)^{-p}
+ (1+t)
^{- \frac{1}{2p} \cdot \frac{3p}{3p-2} + \epsilon }
\, \right) \\[15pt]
\; \; \: \, \, \,
\, \: \: \; \; \quad \qquad \qquad \qquad \qquad \qquad \qquad \,
\left( \, 1 < p \le \displaystyle{\frac{1 + \sqrt{3}}{2}} \, \right),\\[15pt]
C( \, \epsilon, \, p, \, \phi_0, \, \partial _x u_0 \, ) \,
\left( \,
(1+t)^{-\frac{2p+1}{2p}}
+ (1+t)
^{- \frac{1}{2p} \cdot \frac{3p}{3p-2} + \epsilon }
\, \right) \\[15pt]
\; \; \: \, \, \,
\, \: \: \; \; \quad \qquad \qquad \qquad \qquad \qquad \qquad \qquad
\left( \, \displaystyle{\frac{1 + \sqrt{3}}{2}} < p \, \right),
\end{array}
\right.\, \\[15pt]
& \leq \left\{\begin{array} {ll}
C( \, \epsilon, \, p, \, \phi_0, \, \partial _x u_0 \, ) \,
(1+t)^{-{p}} \, \: \; \qquad
\left( \, 1 < p
\le \displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{3p-2}{3}\, \epsilon } } \, \right),\\[15pt]
C( \, \epsilon, \, p, \, \phi_0, \, \partial _x u_0 \, ) \,
(1+t)^{-\frac{3}{2(3p-2)} + \epsilon} \, \: \quad
\left( \,
\displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{3p-2}{3}\, \epsilon } }
< p \, \right)
\end{array}
\right.\,
\end{aligned}\end{aligned}$$ for any $0<\epsilon \ll 1$.
Thus, we get (5.31).
We finally show the $L^{\infty}$-estimate for $\phi$ by using the Gagliardo-Nirenberg inequality. Substituting (5.11) and (5.31) into (4.19), we get $$\begin{aligned}
\begin{aligned}
&\bigl|\bigl|\,
\phi(t) \,
\bigr|\bigr|_{L^{\infty } } \\[5pt]
&\leq \left\{\begin{array} {ll}
C( \, \epsilon, \, p, \, \theta, \, \phi_0, \, \partial _x u_0 \, ) \,
(1+t)
^{-\frac{1}{2p} +
\left( \frac{2p+1}{2p(p+1)} - \frac{p}{p+1} \right) \theta} \\[15pt]
\, \: \: \; \; \quad \qquad \qquad \qquad \qquad \,
\left( \, 1 < p \le
\displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{(p+1)(3p-2)}{3}\, \epsilon } }
\, \right),\\[15pt]
C( \, \epsilon, \, p, \, \theta, \, \phi_0, \, \partial _x u_0 \, ) \,
(1+t)
^{-\frac{1}{2p} +
\left( \frac{2p+1}{2p(p+1)} - \frac{3}{2(p+1)(3p-2)} + \epsilon \right) \theta}\\[15pt]
\, \: \: \; \; \quad \qquad \qquad \qquad \qquad \qquad
\left( \,
\displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{(p+1)(3p-2)}{3}\, \epsilon } }
< p \, \right)
\end{array}
\right.\, \end{aligned}\end{aligned}$$ for $\theta \in (0,1\, ]$ and any $0<\epsilon \ll 1$. Consequently, we do complete the proof of Theorem 3.2.
$L^{r+1}$-estimate for the higher order derivative with $r>p$
=============================================================
In this section, we show the time-decay estimates for the higher order derivative in the $L^{r+1}$-norm with $r>p$, in the case where $\phi_0 \in L^1 \cap L^2$ with $\partial _x u_0 \in L^{p+1} \cap L^{r+1}$, that is, Theorem 3.3.
[**Proposition 6.1.**]{}
The proof of Proposition 6.1 is given by the following three lemmas. Because the proofs of them are similar to those of Lemma 5.4, Lemma 5.5, Lemma 5.6 and Lemma 5.7, we state only here.
[**Lemma 6.1.**]{}
[**Lemma 6.2.**]{}
[**Lemma 6.3.**]{}
[**Proof of Proposition 6.1.**]{} By using (5.31), we estimate the each terms on the right-hand side of (6.2) as $$\begin{aligned}
\begin{aligned}
&C_{\alpha,p,r} \int ^t_0
(1+\tau )
^{\alpha -{\frac{2p+r+1}{3p+1}}}
\left( \,
\int _{-\infty}^{\infty}
\left|\, \partial _x u \, \right|^{p+1}
\, \mathrm{d}x \,
\right)^{\frac{p+2r+1}{3p+1}}
\, \mathrm{d}\tau \\[5pt]
& \leq \left\{\begin{array} {ll}
C( \, \alpha, \, \epsilon, \, p, \, r, \, \phi_0, \, \partial _x u_0 \, ) \,
\displaystyle{ \int ^t_0
(1+\tau )
^{\alpha - \frac{2p+r+1}{3p+1} -{\frac{p(p+2r+1)}{3p+1}}}
\, \mathrm{d}\tau } \\[15pt]
\, \: \: \; \; \quad \qquad \qquad \qquad \qquad \qquad \qquad \,
\left( \, 1 < p \le
\displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{3p-2}{3}\, \epsilon } }
\, \right),\\[15pt]
C( \, \alpha, \, \epsilon, \, p, \, r, \, \phi_0, \, \partial _x u_0 \, ) \,
\displaystyle{ \int ^t_0
(1+\tau )
^{\alpha - \frac{2p+r+1}{3p+1} -{\frac{3(p+2r+1)}{2(3p+1)(3p-2)}}
+ \frac{p+2r+1}{3p+1} \epsilon}
\, \mathrm{d}\tau } \\[15pt]
\, \: \: \; \; \quad \qquad \qquad \qquad \qquad \qquad \qquad \qquad
\left( \, \displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{3p-2}{3}\, \epsilon } }
< p \, \right)
\end{array}
\right.\, \\[5pt]
& \leq \left\{\begin{array} {ll}
C( \, \alpha, \, \epsilon, \, p, \, r, \, \phi_0, \, \partial _x u_0 \, ) \,
(1+t )
^{\alpha - \frac{2pr+p^2+r}{3p+1} } \\[15pt]
\, \: \: \; \; \quad \qquad \qquad \qquad \qquad \qquad \qquad \,
\left( \, 1 < p \le
\displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{3p-2}{3}\, \epsilon } }
\, \right),\\[15pt]
C( \, \alpha, \, \epsilon, \, p, \, r, \, \phi_0, \, \partial _x u_0 \, ) \,
(1+t )
^{\alpha - \frac{6p(r-p)+7p+2r+3}{2(3p+1)(3p-2)}
+ \frac{p+2r+1}{3p+1} \epsilon} \\[15pt]
\, \: \: \; \; \quad \qquad \qquad \qquad \qquad \qquad \qquad \qquad
\left( \, \displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{3p-2}{3}\, \epsilon } }
< p \, \right),
\end{array}
\right.\, \end{aligned}\end{aligned}$$ $$\begin{aligned}
\begin{aligned}
&C_{p,r} \int ^t_0 (1+\tau )^\alpha
\left( \,
\int _{\partial _x u < 0 }
\left|\, \partial _x u \, \right|^{p+1}
\, \mathrm{d}x \,
\right)^{\frac{p+2r+2}{3p}}
\, \mathrm{d}\tau \\
& \leq C_{p,r} \int ^t_0 (1+\tau )^\alpha
\left( \,
\int _{-\infty}^{\infty}
\left|\, \partial _x \phi \, \right|^{p+1}
\, \mathrm{d}x \,
\right)
\| \, \partial _x u (\tau) \, \| _{L^{p+1}}
^{\frac{2(p+1)(r-p+1)}{3p}}
\, \mathrm{d}\tau \\[5pt]
& \leq \left\{\begin{array} {ll}
C( \, \alpha, \, \epsilon, \, p, \, r, \, \phi_0, \, \partial _x u_0 \, ) \,
\displaystyle{ \int ^t_0
(1+\tau )
^{\alpha - \frac{2(r-p+1)}{3} }
\| \, \partial _x \phi (\tau) \, \| _{L^{p+1}}^{p+1}
\, \mathrm{d}\tau } \\[15pt]
\, \: \: \; \; \; \; \; \quad \qquad \qquad \qquad \qquad \qquad \qquad \,
\left( \, 1 < p \le
\displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{3p-2}{3}\, \epsilon } }
\, \right),\\[15pt]
C( \, \alpha, \, \epsilon, \, p, \, r, \, \phi_0, \, \partial _x u_0 \, ) \,
\displaystyle{ \int ^t_0
(1+\tau )
^{\alpha - \frac{r-p+1}{p(3p-2)} + \frac{2(r-p+1)}{3p} \epsilon}
\| \, \partial _x \phi (\tau) \, \| _{L^{p+1}}^{p+1}
\, \mathrm{d}\tau } \\[15pt]
\, \: \: \; \; \; \; \; \quad \qquad \qquad \qquad \qquad \qquad \qquad \qquad
\left( \, \displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{3p-2}{3}\, \epsilon } }
< p \, \right)
\end{array}
\right.\,
\end{aligned}\end{aligned}$$ for any $0<\epsilon \ll 1$.\
By using Lemma 5.8 with $$\begin{aligned}
\begin{aligned}
\alpha \mapsto \left\{\begin{array} {ll}
\alpha-\displaystyle{\frac{2(r-p+1)}{3}}
\, \, \: \; \quad \quad \qquad \qquad
\left( \, 1 < p \le
\displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{3p-2}{3}\, \epsilon } }
\, \right),\\[15pt]
\alpha
-\displaystyle{\left( \,
\frac{r-p+1}{p(3p-2)} - \frac{2(r-p+1)}{3p} \epsilon
\, \right)}
\quad
\left( \, \displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{3p-2}{3}\, \epsilon } }
< p \, \right)
\end{array}
\right.\,
\end{aligned}\end{aligned}$$ and $q=2$, we get $$\begin{aligned}
\begin{aligned}
&C_{p,r} \int ^t_0 (1+\tau )^\alpha
\left( \,
\int _{\partial _x u < 0 }
\left|\, \partial _x u \, \right|^{p+1}
\, \mathrm{d}x \,
\right)^{\frac{p+2r+2}{3p}}
\, \mathrm{d}\tau \\[5pt]
& \leq \left\{\begin{array} {ll}
C( \, \alpha, \, \epsilon, \, p, \, r, \, \phi_0, \, \partial _x u_0 \, ) \,
(1+t )
^{\alpha - \frac{4p(r-p)+4p+3}{6p} } \\[15pt]
\, \: \: \; \; \quad \qquad \qquad \qquad \qquad \,
\left( \, 1 < p \le
\displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{3p-2}{3}\, \epsilon } }
\, \right),\\[15pt]
C( \, \alpha, \, \epsilon, \, p, \, r, \, \phi_0, \, \partial _x u_0 \, ) \,
(1+t )
^{\alpha - \frac{p+2r}{2p(3p-2)} + \frac{2(r-p+1)}{3p} \epsilon} \\[15pt]
\, \: \: \; \; \quad \qquad \qquad \qquad \qquad \qquad
\left( \, \displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{3p-2}{3}\, \epsilon } }
< p \, \right)
\end{array}
\right.\,
\end{aligned}\end{aligned}$$ for any $0<\epsilon \ll 1$.\
Substituting (6.3) and (6.5) into (6.2), we have $$\begin{aligned}
\begin{aligned}
&(1+t)^\alpha
\| \, \partial _x u (t)\, \| _{L^{r+1}}^{r+1} \\ & \quad
+ \int ^t_0 (1+\tau )^\alpha \int _{-\infty}^{\infty}
\bigl| \, \partial _x u \, \bigr|^{p+r-2}
\left( \, \partial _x^2 u \, \right)^2
\, \mathrm{d}x \mathrm{d}\tau \\
& \quad
+ \int ^t_0 (1+\tau )^\alpha
\int _{\partial _x u \geq 0}
f''(u) \left|\, \partial _x u \, \right|^{r+2}
\, \mathrm{d}x \mathrm{d}\tau \\
& \leq C_{\alpha,p,r}
\| \, \partial _x u_{0} \, \| _{L^{r+1}}^{r+1} \\[5pt] & \quad +
\left\{\begin{array} {ll}
C( \, \alpha, \, \epsilon, \, p, \, r, \, \phi_0, \, \partial _x u_0 \, )
(1+t)^{\alpha}\\[5pt]
\times
\left( \,
(1+t)
^{- \frac{2pr+p^2+r}{3p+1}}
+ (1+t)
^{- \frac{4p(r-p)+4p+3}{6p} }
\, \right) \\[15pt]
\, \: \: \; \; \quad \qquad \qquad \qquad \qquad \qquad \qquad \,
\left( \, 1 < p \le
\displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{3p-2}{3}\, \epsilon } }
\, \right),\\[15pt]
C( \, \alpha, \, \epsilon, \, p, \, r, \, \phi_0, \, \partial _x u_0 \, )
(1+t)^{\alpha}\\[5pt]
\times
\left( \,
(1+t)
^{- \frac{6p(r-p)+7p+2r+3}{2(3p+1)(3p-2)}
+ \frac{p+2r+1}{3p+1} \epsilon}
+ (1+t)
^{- \frac{p+2r}{2p(3p-2)}
+ \frac{2(r-p+1)}{3p} \epsilon}
\, \right) \\[15pt]
\, \: \: \; \; \quad \qquad \qquad \qquad \qquad \qquad \qquad \qquad
\left( \, \displaystyle{\frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{3p-2}{3}\, \epsilon } }
< p \, \right)
\end{array}
\right.\, \\[5pt]
\end{aligned}\end{aligned}$$ for any $0<\epsilon \ll 1$.\
We also note the following: if $1 < p
\le \frac{1}{3} +
\sqrt{\frac{11}{18} - \frac{3p-2}{3}\, \epsilon} $, then $r > p > \frac{18p^3-17p^2-16p-3}{2(2p+1)}$ and $$(1+t)^{- \frac{4p(r-p)+4p+3}{6p} }
\leq (1+t)^{- \frac{2pr+p^2+r}{3p+1}}, $$ and if $\epsilon
< \frac{3(r-p)(p-1)(3p+1)}{(3p-2)\, \left| \, 9p^2-p-2r-2 \, \right|}$, then $$(1+t)^{- \frac{6p(r-p)+7p+2r+3}{2(3p+1)(3p-2)}
+ \frac{p+2r+1}{3p+1} \epsilon}
\leq (1+t)^{- \frac{p+2r}{2p(3p-2)}
+ \frac{2(r-p+1)}{3p} \epsilon} \; \;
( \, \forall p>1, \, \forall r>p \, ). $$
Thus, we do complete the proof of Proposition 6.1.
Discussion
==========
In this section, we discuss the time-decay rates in our main theorems. To do that, we recall the time-decay rates of solutions to a Cauchy problem for the simplest $p$-Laplacian evolution equation without convestive term: $$\begin{aligned}
\left\{\begin{array}{ll}
\partial_tu -
\mu \,
\partial_x \left( \,
\left| \, \partial_xu \, \right|^{p-1} \partial_xu \,
\right) =0
\qquad &(t>0, x\in \mathbb{R}), \\[5pt]
u(0,x) = u_0(x) \qquad &( x \in \mathbb{R} ),\\[5pt]
\displaystyle{\lim_{x\to \pm \infty}} u(t,x) =0
\qquad &\bigl( t \ge 0 \bigr),
\end{array}
\right.\,\end{aligned}$$ where, $u=u(t,x)$ denotes the unknown function of $t>0$ and $x\in \mathbb{R}$. The theorems concerning the time-decay estimates to the problem (7.1) are as follows (the proofs are similar to those in the previous sections).
[**Theorem 7.1.**]{}
[**Theorem 7.2.**]{}
[**Theorem 7.3.**]{}
It is clear that the time-decay rates in the $L^q$-norm ($2 \leq q \leq \infty$ or $1 \leq q \leq \infty$) for the lower order $u-\tilde{u}$ or $u-u^r$ in Theorems 1.1, 1.2, 1.4 and 1.5 are quite or almost the same as $u$ in Theorem 7.1 and 7.2. This shows that the affection to the time-decay from the formulation of the equation $$\partial_tu -
\mu \,
\partial_x \left( \,
\left| \, \partial_xu \, \right|^{p-1} \partial_xu \,
\right) =0$$ is stronger than those from the asymptotic states, the rarefaction wave $u^r$ (or $U^r$) or the constant states $\tilde{u}$ (and also from the shape of the flux function $f$, see (4.2), (5.3) and (5.10)). In fact, the time-decay in (4.16) is faster than that in (4.15) without $\alpha \gg 1$ in Section 4. On the other hand, the time-decay rates in the $L^{p+1}$-norm or the $L^{r+1}$-norm ($r>p$) for the higher order $\partial _x u$ or $\partial _x u-\partial _x u^r$ in Theorems 1.2, 1.3, 1.5, 1.6, 7.2 and 7.3 are all different from with each other. The reason for the difference must arise from that the asumptions for the flux function $f$ and the far field states $u_{\pm}, \, \tilde{u}$, and the characteristic propaties of the asymptotic states ($u^r$ or $\tilde{u}$) affect (in some sense) the strong nonlinearlity of the higher order $\partial _x u$ (not $u$), that is, $p$-Laplacian type viscosity (see (5.18), (5.19), (5.25), (5.26), (5.33) in Section 5 and (6.5) in Section 6). However, the optimality of the all time-decay rates still remains open.
[**Acknowledgement.**]{}The auther thanks Professor Akitaka Matsumura for his significant comments and kind advices.
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|
There has been limited effort to study the role of iron in association with inflammation and treatment or prevention of cancer, especially from dietary sources or complementary medicines. A unique class of compounds from cranberries, known as A-type proanthocyanidins (A-PACs), have iron chelating properties and are the major component of cranberry fractions that have exhibited anti-tumor effects against several human cancer cell lines. Cranberry A-PAC fractions have also inhibited the inflammatory mediator Interleukin(IL)-6, a cytokine that affects iron metabolism and contributes to anemia of inflammation from chronic disease. The proposed research project will investigate the anti-tumor activities of A-PACs and their effects on anemia in relation to inflammation, and iron metabolism. The iron biomarkers, hepcidin, ferroportin, transferrin receptor and the inflammatory cytokines, IL-1alpha and IL-6 are of particular interest for this project. The anti-tumor activity of A-PACs will be tested at three different levels in vitro and in vivo with melanoma and leukemia cell lines. Tumor cells and mice implanted with tumors, will be treated with 1) a cranberry supplement with high A-PAC content 2) an A-PAC mixture consisting of mostly A-PAC dimers/trimers; 3) an A-PAC dimer or trimer. Iron metabolism and inflammation markers will be evaluated by qPCR, immunohistochemistry or other methods after treatment with A-PACs. An anemia of inflammation model recently developed by our lab will prolong the life of mice with tumors by an inducible suicide gene and provide systemic effects more similar to humans. Several hematological parameters, iron, and inflammation biomarkers will be analyzed in this model with and without the treatment of A-PACs. In addition, structural studies of A-PACs and their anti-tumor effects will be conducted in vitro by comparison of an A-PAC dimer with a similar compound lacking the ether bond. Changes in reactive oxygen species (ROS) and prosurvival factors of tumor cells treated with A-PACs in vitro will also be assessed to better understand the pathways involved in anti-tumor activity. Results from this research will provide more information about the mechanisms of A- PACs in relation to anti-tumor activities, altered iron metabolism and anemia of inflammation. These studies will also provide medical research training in hematology/oncology and further characterize the association of cancer with iron metabolism and inflammatory states. |
Hillside Strangler
The Hillside Strangler, later the Hillside Stranglers, is the media epithet for one, later two, American serial killers who terrorized Los Angeles between October 1977 and February 1978, with the nicknames originating from the fact that many of the victims' bodies were discovered in the hills surrounding greater Los Angeles. It was initially believed that only one individual was responsible for the killings. The police, however, knew from the positions of the bodies that two individuals were working together, but withheld this information from the press. These two individuals were eventually discovered to be cousins Kenneth Bianchi and Angelo Buono Jr., who were later convicted of kidnapping, raping, torturing and murdering 10 women and girls ranging in age from 12 to 28 years old.
The Hillside Strangler murders began with the deaths of three sex workers who were found strangled and dumped naked on hillsides northeast of Los Angeles between October and early November 1977. It was not until the deaths of five young women who were not sex workers, but girls who had been abducted from middle-class neighborhoods, that the media attention and subsequent "Hillside Strangler" moniker came to prominence.
There were two more deaths in December and February before the murders abruptly stopped. An extensive investigation proved fruitless until the arrest of Bianchi in January 1979 for the murder of two more young women in Washington State and the subsequent linking of his past to the Strangler case. The most expensive trial in the history of the California legal system at that time followed, with Bianchi and Buono eventually being found guilty of these crimes and sentenced to life imprisonment.
Background
In January 1976, Kenneth Bianchi left Rochester, New York and moved to Los Angeles, California to live with his cousin, Angelo Buono Jr. Buono provided a strong role model for the docile Bianchi. When Bianchi was short of money, Buono came up with the idea of getting some girls to work for them as prostitutes. Two teenage runaways, Sabra Hannan and Becky Spears, met Bianchi and Buono and, once under their control, were forced to prostitute themselves. Eventually, Spears happened to meet lawyer David Wood, who was appalled at her situation and arranged for her to escape from the city.
Encouraged by Spears' escape, Hannan ran away from Bianchi and Buono a short time later. With their pimping income gone, they had to find more teenage girls. Impersonating police officers, they eventually found another young woman and installed her in the previous girl's bedroom. Also, they bought from a prostitute named Deborah Noble a supposed "trick list" with names of men who frequented prostitutes. Deborah and her friend, Yolanda Washington, delivered the trick list to Buono in October 1977.
Murders
Yolanda Washington
Yolanda happened to mention to Buono that she always worked on a certain stretch of Sunset Boulevard. When Bianchi and Buono found that Deborah had deceived them about the list but were unable to find her, they decided to take out their rage on Yolanda. Her naked body was found on October 17, 1977, on a hillside near the Ventura Freeway, and Detective Frank Salerno of the Los Angeles Sheriff's Department was called to the scene. It was determined that the corpse was cleaned before being dumped; faint marks were visible around the neck, wrists, and ankles where a rope had been used. The victim had also been raped.
Judy Miller
On November 1, 1977, police were called to Alta Terrace Drive in La Crescenta, a neighborhood 12 miles north of downtown Los Angeles, where the body of a teenage girl was found naked, face up on a parkway in a middle-class residential area. The homeowner had covered her with a tarp in the early morning hours to prevent the neighborhood children from viewing her on their way to school. Ligature marks were on her neck, wrists and ankles, indicating to police she was bound and strangled. The body had been dumped, indicating she was killed elsewhere.
Det. Salerno also found a small piece of light-colored fluff on her eyelid and saved it for the forensic experts. A coroner's report further detailed that she had been raped and sodomized. The girl, who was described as being "small and thin, weighing about 90 pounds and appearing to be about 16 years old", was eventually identified as 15-year-old Judith Lynn Miller, a former student of Hollywood High School, runaway and occasional sex worker.
Judith was last seen alive on October 31, 1977, talking to a man driving a large two-tone sedan on Sunset Blvd next to Carneys Express Limited. The stranglers told her they were undercover police officers, handcuffed her, and took her to Buonos Upholstery Shop on Colorado Blvd in Glendale where she was murdered.
Lissa Kastin
Five days later, on November 6, 1977, the nude body of another woman was discovered near the Chevy Chase Country Club, in Glendale. Like Miller, she bore five-point (neck, wrists and ankles) ligature marks and of having been strangled and brutally raped, but not sodomized. The woman was identified as 21-year-old waitress Elissa Teresa "Lissa" Kastin, who was last seen leaving the restaurant where she worked the night before her body was discovered.
Kastin was also a professional dancer for The L.A. Knockers and unlike the two previous victims was not a prostitute, drug user or runaway. The stranglers followed Kastin after she was seen driving home from work, pulled her over on the street she lived on, presented a fake police badge, and told her that they were detectives. They then handcuffed her and told her they needed to take her in for questioning.
Aborted murder of Catharine Lorre Baker
At some point in early November 1977, the two men approached 24-year-old Catharine Lorre Baker, the daughter of actor Peter Lorre — famous for his role as a serial killer in Fritz Lang's film M — with the intent of abducting and killing her. However, when they found a picture of her sitting on her father's lap among her identification, they let her go without incident. She did not realize who the men were until they were arrested, at which point she recalled that two men flashing L.A. police badges had approached her in the past.
Dolly Cepeda and Sonja Johnson
On Sunday, November 13, 1977, two girls, 12-year-old Dolores Ann "Dolly" Cepeda and 14-year-old Sonja Marie Johnson, boarded an RTD bus in front of The Eagle Rock Plaza and headed home. The last time they were seen was getting off the bus on York Blvd and Ave 46 and approaching a two-tone sedan which reportedly had two men inside. Their two corpses were found by a nine-year-old boy who had been treasure hunting in a trash heap on a hillside near Dodger Stadium on November 20, 1977. Both of the girls' bodies had already begun to decompose. It was determined that they had been strangled and raped.
Kristina Weckler
Earlier that same day, November 20, 1977, hikers found the naked body of twenty-year-old Kristina Weckler, a quiet honors student at the Art Center College of Design deemed by Detective Bob Grogan of the Los Angeles Police Department to be a "loving and serious young woman who should have had a bright future ahead of her", on a hillside between Glendale and Eagle Rock. When found by Grogan, ligature marks were on her wrists, ankles and neck, and when he turned her over, bruises on her breasts were obvious and blood oozed from her rectum. Unlike the first three victims there were two puncture marks on her arm, but no signs of the needle tracks that indicated a drug addict. It was later revealed that Weckler had been injected with Windex, a hard-surface cleaner.
Jane King
On November 23, 1977, the badly decomposed body of 28-year-old Evelyn Jane King, an actress who had gone missing around November 9, was found near the Los Feliz off-ramp of the Golden State Freeway. The severity of decomposition prevented determination as to whether she had been raped or tortured but she had been strangled like the others. In response authorities created a task force — initially composed of 30 officers from the LAPD, the Sheriff's Department and the Glendale Police Department — to catch the predator now dubbed the "Hillside Strangler".
Lauren Wagner
On November 29, 1977, police found the body of eighteen-year-old Lauren Rae Wagner, a business student who lived with her parents in the San Fernando Valley, in the hills around Los Angeles's Mount Washington. She had ligature marks on her neck, ankles and wrists. There were also burn marks on her hands indicating she was tortured. Lauren's parents had expected her to come home before midnight, and the next morning when they found her car parked across the street with the door ajar, her father questioned the neighbors.
He found that the woman who lived in the house where Lauren's car had been parked saw her abduction. This woman stated that she saw two men: one was tall and young, the other one was older and shorter with bushy hair. She also stated that she heard Wagner cry out, "You won't get away with this!", during her abduction.
Kimberly Martin
On December 14, 1977, the body of 17-year-old sex worker Kimberly Diane Martin, which was naked and showed signs of torture, was found on a deserted lot near Los Angeles City Hall. Martin had previously joined a call girl agency because she feared exposing herself on the streets with the Strangler on the loose. The killers happened to place a call to her agency from a Hollywood Public Library pay phone and she was the call girl who was dispatched. When the police investigated the apartment she had been dispatched to, they found it vacant and broken into.
Cindy Hudspeth
The final victim was discovered in Los Angeles on February 17, 1978, when a helicopter pilot spotted an orange Datsun abandoned off a cliff on the Angeles Crest Highway. Police responded to the scene and found the body of the car's owner, twenty-year-old Cindy Lee Hudspeth - a student and part-time waitress - in the trunk. Her corpse again showed ligature marks, and she had been raped and tortured. It appeared she had been strangled and put in the trunk of her car, which was then pushed off the cliff above.
Investigation and trial
In January 1979, after intensive investigation, police charged Bianchi and Buono with the crimes. Bianchi had fled to Bellingham, Washington, where he was soon arrested by Bellingham Police Department for raping and murdering two women he had lured to a home for a house-sitting job. Bianchi attempted to set up an insanity defense, claiming that he had dissociative identity disorder and that a personality separate from himself committed the murders. Court psychologists, notably Dr. Martin Orne, observed Bianchi and found that he was faking, so Bianchi agreed to plead guilty and testify against Buono in exchange for leniency.
At the conclusion of Buono's trial in 1983, Presiding Judge Ronald M. George, who later became Chief Justice of the California Supreme Court, stated during sentencing, "I would not have the slightest reluctance to impose the death penalty in this case were it within my power to do so. Ironically, although these two defendants utilized almost every form of legalized execution against their victims, the defendants have escaped any form of capital punishment." Bianchi is serving a life sentence at the Washington State Penitentiary in Walla Walla. Buono died of a heart attack on September 21, 2002, at Calipatria State Prison in California, where he was serving a life sentence.
Veronica Compton
In 1980, Bianchi began a relationship with Veronica Compton. During his trial, she testified for the defense. She was later convicted and imprisoned for attempting to strangle a woman she had lured to a motel in an attempt to have authorities believe that the Hillside Strangler was still on the loose and the wrong man was imprisoned. Bianchi had given her some smuggled semen to use to make it look like a rape/murder committed by the Hillside Strangler. She was released in 2003.
Media
Film adaptations
Television
The Hillside Stranglers have been referenced three times on the police procedure crime drama Criminal Minds. C. Thomas Howell (as mentioned above) later portrayed George Foyet/The Reaper in the show's fourth and fifth seasons.
See also
Alphabet murders
General:
List of serial killers in the United States
References
Cited works and further reading
External links
"'Hillside Strangler' dies in prison", CNN, September 22, 2002
Crime Library's story on the Hillside Stranglers
Category:1977 in California
Category:1977 murders in the United States
Category:1978 in California
Category:1978 murders in the United States
Category:American serial killers
Category:American people convicted of child sexual abuse
Category:Crimes in California
Category:Criminal duos
Category:Male serial killers
Category:Murder in California
Category:Rapes in the United States
Category:Torture in the United States
Category:Incidents of violence against women |
[Effect of sterols on melittin incorporation into liposomal membranes].
Effects of various sterols on the values of intensity, spectrum position and polarization of tryptophan fluorescence (P) of melittin incorporated in lecithin liposomes at different lipid/protein molar ratios (Ri) were studied. A difference in sterol effects has been revealed at the values of Ri > 5. At Ri < 5, fluorescence parameters were determined mainly by melittin in the aqueous solution. Assuming that melittin was bound to lecithin, the lecithin/melittin binding ratio was found to be in the range of 25-50. Unlike cholesterol and stigmasterol, the incorporation into membranes of ergosterol and 7-dehydrocholesterol produced a decrease in the intensity of tryptophan fluorescence and an increase in the P value. This difference might result from the presence of an additional double bond in one of sterol rings of ergosterol and 7-dehydrocholesterol molecules. Analysis of the results obtained enabled us to suggest that the structure of the steroid B ring is responsible for the effect exerted by sterols on melittin-lipid interactions. |
An edible building made of chocolate! | A sculpture with brains!| A treat for racket-sports lovers| and more
Editorial
Dear IAnDians,
Trust you all had a wonderful festive season with your fill of sweetmeats amid the buoyancy of familial togetherness!
As we enjoyed the same with a brief four-day break, we were warmly welcomed back to some exciting out-of-box design stories that we have collated for you on priority. So, we have for you the sculpture that can change to your likeness just as you decide to interact with it; the beautifully designed architectural Wada Sports store in Japan that is no less than a racket museum; and our special story that makes it to the cover - the chocolate building! Edible therefore sustainable, Carlo Ratti says the only challenge he faced building this pavilion was that parts of it got eaten up along the construction...
product hub
testimonials
To read what some of our readers-patrons have to say about us: click hereTeam India Art n Design looks forward to hear from you too and add your valueable opinion to our long list of satisfied readers. To send us an email :click here |
U.K. Minister Holds Talks With Meat Industry Over Contamination
Feb. 9 (Bloomberg) -- U.K. Environment Secretary Owen
Paterson said he has called an “urgent” meeting today with the
Food Standards Agency and meat retailers and suppliers over
reports by some supermarkets that horsemeat has been found in
some ready meals meant to contain beef.
“It’s totally unacceptable that people have been sold
something that is not what they think it is,” Paterson said in
a statement on his department’s website late yesterday.
“Investigations are going on across Europe, and the evidence so
far suggests that it’s either criminal activity or gross
negligence.”
Paterson said Findus has notified the FSA that significant
quantities of horse meat had been found in its frozen beef
lasagnes and that two cases of frozen burgers from Tesco and the
lasagne from Findus are linked to suppliers in Ireland and
France respectively.
“In addition, the FSA has ordered food businesses to test
all their processed beef products and is conducting its own
survey of beef products, including those supplied to schools and
hospitals,” Paterson said. “The FSA has said that unless there
is advice to avoid a specific product, there is no reason for
people to change their shopping habits. There is no reason to
believe that processed beef products currently on sale are
unsafe.” |
The discussion below is merely provided for general background information and is not intended to be used as an aid in determining the scope of the claimed subject matter.
Aspects of the present invention relate to a container having a box shape and comprising a bottom wall, side walls forming a circumferential wall of the container, a strap which forms four lifting loops at the upper side of the container and which is fixed to the side walls diagonally such that the strap forms a V-shape on each of said side walls between two adjacent lifting loops.
Such a container is known in the art. The lifting loops are located at the top of the container for carrying the container by means of a forklift truck. Due to the V-shapes of the strap on the side walls the load stress in the container is distributed evenly. |
Q:
Gradle sync failed: Unable to start the daemon process with no specific main class defined
I'm using android studio 3.2.1 and seeing this error
Unable to start the daemon process.
This problem might be caused by incorrect configuration of the daemon.
For example, an unrecognized jvm option is used.
Please refer to the user guide chapter on the daemon at https://docs.gradle.org/3.3/userguide/gradle_daemon.html
Please read the following process output to find out more:
-----------------------
Error: Could not find or load main class =
This started happening all of a sudden and I don't know what changed and how to fix this?
A:
Your issue is related with your jvmargs on your gradle properties file.
For example, an unrecognized jvm option is used
You can try the following:
Open your gradle.properties
Add the following:
org.gradle.jvmargs=-Xmx2048m -XX:MaxPermSize=512m -XX:+HeapDumpOnOutOfMemoryError -Dfile.encoding=UTF-8
(it can be more, depends on your machine memory capacity).
Save the file, reboot project
—-
From the documentation:
org.gradle.jvmargs=(JVM arguments)
Specifies the JVM arguments used
for the Gradle Daemon. The setting is particularly useful for
configuring JVM memory settings for build performance.
|
This article is part of my SQL Server CI/CD Series. In it I will be talking about creating artifacts related to SQL Server in your the CI part of the build chain.
What is an artifact?
First lets define an artifact within the narrow scope of Continuous Integration (CI) an artefact is anything created during a build that is retained for download. Typically this is a zip file or other package of the compiled application and a html rendering of test reports.
Artifacts we will produce
We are going to produce the following artifacts:
A backup of the database taken after all tests are run
A dacpac of the schema
Output of some queries we run through SQLCMD
We can produce more artifacts like SQL Unit test reports, database diagrams, or even scripting out the entire database. We will do that in a future article. For now, we will stick to these three artifacts.
Why do we want to produce these artifacts?
Just because you can’ doesn’t mean you should. You don’t want to create artifacts unless they will be used. So what is the point of producing each artifact.
Database Backup
In a CI process that involves SQL Server, you’re probably going to create a database. You are then going to modify it as part of your testing. In the end you are going to end up with a “gently used” database. You will likely have all your schema setup, any “static” data, and some test data. You’ll have some statistics, and fragmentation as well. You might want to restore the backup to your laptop and inspect all this stuff. Perhaps manually verify that your assertions in your tests are covering what you think they should.
You also might want a copy of the database that someone can restore to run a local copy of their code, or reports against.
Finally, if any of your CD pipelines are designed to create a fresh database, your going to need this artifact in that CD pipeline. As a matter of fact you might end up creating two backups. One at the point where your database is in a clean “initial state,” and another after all your automated testing has been run.
Dacpac
I hold the strong opinion that the best way to deploy schema changes to a database is a dacpac. You’re welcome to disagree with me, and like everything else in SQL Server, the answer it depends. However, My advice in these articles will always be around the assumption that the dacpac is the gold standard for automated deployments of schema changes.
That being said, if you prefer to use scripts or another tool to manage schema changes, then you are wasting storage and build server CPU creating a dacpac.
Sqlcmd output
Sometime you just want to generate a quick and dirty report in T-SQL to look at. Maybe there is information you want to be aware of, but don’t necessarily want to fail a build, like index fragmentation after the tests are run. Perhaps someone just wants a report to look at after a test run.
Regardless, sometimes sqlcmd –i inputfile.sql –o outputfile.txt is good enough to get you home.
How do we create these artifacts in AppVeyor?
In our introduction I stated we would use AppVeyor as our CI tool, because its free for open source projects, and because its simplicity makes it easy to explicitly show how we accomplish tasks. The steps are all segments of appveypr.yml.
First of all, we need to start SQL Server. We use the services section of appveyor.yml to specify what services to start. I happen to use SQL Server 2016 because that’s the version of SQL Server that Always Encrypted was introduced on.
services: - mssql2016
Now, every step we use to get the database to its final step is a subject for another blog. I’ll just simply this.
We use environment variables to configure the connection information. We create the database with sqlcmd. Other stuff happens to the database.
The relevant environment variables in our case are:
environment: SQL_SERVER_INSTANCE: (local)\SQL2016 SQL_SERVER_USER: AlwaysEncryptedOwner SQL_SERVER_PASSWORD: 7aO!z@xUu!4r6EvD#D&l$sz6&h^rhxL6fzAHMpnOga@LO*WdsEdpfh4^Egtl SQL_SERVER_DATABASE: AlwaysEncryptedSample SQL_SERVER_BACKUP_FILE: $(SQL_SERVER_DATABASE).bak SQL_SERVER_DACPAC: $(SQL_SERVER_DATABASE).dacpac SQL_SERVER_VERIFICATION_LOG: $(SQL_SERVER_DATABASE).verification.log
Our creation script is run here:
before_build: - cmd: sqlcmd -S "%SQL_SERVER_INSTANCE%" -i .\appveyor\init.sql
The script itself is:
CREATE DATABASE [$(SQL_SERVER_DATABASE)]; GO CREATE LOGIN $(SQL_SERVER_USER) WITH PASSWORD = '$(SQL_SERVER_PASSWORD)'; GO -- Needed for dacpac creation -- GRANT VIEW ANY DEFINITION TO $(SQL_SERVER_USER); -- GO USE [$(SQL_SERVER_DATABASE)]; GO CREATE USER $(SQL_SERVER_USER); ALTER ROLE db_owner ADD MEMBER $(SQL_SERVER_USER); GO
It goes without saying that all SQL Server services on AppVeyor build machines use mixed mode authentication and the user that executes AppVeyor steps is a system administrator on all SQL Server instances.
Creating the sql login/user is superfluous, and a step I might remove from that script.
Other stuff happening in the database is the part I’m going to brush over. We now have an empty database that we can perform artifact creating operations on.
Creating the Artifacts
As of the time I wrote this article all my sql artifacts are created in after_build . This is before unit tests are run. None of my tests or any subsequent steps currently modify the database. At this point these artifacts operate on a “fresh” database. Moving them to after_test would give me artifacts that have the test result data in them, if any.
after_build: - cmd: sqlcmd -S "%SQL_SERVER_INSTANCE%" -d %SQL_SERVER_DATABASE% -W -i .\appveyor\schema_verification.sql -o %SQL_SERVER_VERIFICATION_LOG% - cmd: sqlcmd -S "%SQL_SERVER_INSTANCE%" -Q "BACKUP DATABASE [$(SQL_SERVER_DATABASE)] TO DISK='$(SQL_SERVER_BACKUP_FILE)' WITH FORMAT, COMPRESSION, STATS=10;" - ps: Move-Item -Path (Join-Path $env:SQL_SERVER_BACKUP_DIRECTORY "$($env:SQL_SERVER_BACKUP_FILE)") -Destination $env:APPVEYOR_BUILD_FOLDER - cmd: sqlpackage.exe /Action:Extract /TargetFile:"%SQL_SERVER_DACPAC%" /SourceServerName:"%SQL_SERVER_INSTANCE%" /SourceDatabaseName:%SQL_SERVER_DATABASE%
Right now schema_verification.sql looks like this:
PRINT 'Tables in database:' SELECT QUOTENAME(s.name) + '.' + QUOTENAME(t.name) AS [Table Name] FROM sys.tables t INNER JOIN sys.schemas s ON s.schema_id = t.schema_id;
I was actually using this to manually verify that the tables were being created. This is a stop gap for actual automated tests of the SQL Schema.
Also a note on the Move-Item. AppVeyor only lets you create artifacts from files inside the folder where the git repo is checked out. I probably could just specify the full path of the backup file in the CREATE BACKUP T-SQL statement. I’m pretty sure the image is setup so there would be no security issues.
Finally, a note on the environment variables used by the Move-Item invocation. SQL_SERVER_BACKUP_DIRECTORY is set from data in the registry so I need powershell to set it dynamically like so.
install: - ps: $env:SQL_SERVER_BACKUP_DIRECTORY=(Get-ItemProperty "HKLM:\Software\Microsoft\Microsoft SQL Server\MSSQL13.SQL2016\MSSqlServer").BackupDirectory
And APPVEYOR_BUILD_FOLDER is provided to us already. That’s the folder where the git repo is checked out.
So now that we have created these artifacts, we must publish them. This is where the artifacts section of the yaml files comes in.
artifacts: - path: $(SQL_SERVER_BACKUP_FILE) name: Database backup type: file - path: $(SQL_SERVER_DACPAC) name: DACPAC type: file - path: $(SQL_SERVER_VERIFICATION_LOG) name: Verifiction Query Results type: file - path: $(MSBUILD_LOG_FILE) name: MSBuild BInary Log type: file
So as you can see, any file we can make via powershell, the command line or any of the tooling the AppVeyor images provides us can become an artifact. Artifacts are by no means limited to SQL Server, that’s simply the focus of this blog series. |
Notifications
Prime Minister Justin Trudeau and U.S. President Barack Obama announced a ban on offshore oil and gas activity in the Arctic on the same day. The North American leaders say it's part of their commitment to protecting the North from climate change.
Canadian drilling restriction will be reviewed every 5 years, but U.S. ban is permanent
Prime Minister Justin Trudeau and U.S. President Barack Obama, pictured in Ottawa last June, announced a drilling ban in Arctic waters in a joint statement Tuesday. (Sean Kilpatrick/Canadian Press)
Prime Minister Justin Trudeau and U.S. President Barack Obama announced a ban on offshore oil and gas activity in the Arctic in a joint statement issued Tuesday.
"Today, President Obama and Prime Minister Trudeau are proud to launch actions ensuring a strong, sustainable and viable Arctic economy and ecosystem, with low-impact shipping, science-based management of marine resources, and free from the future risks of offshore oil and gas activity," the statement read.
Obama has permanently banned oil and gas development in U.S. waters in the Chukchi and Beaufort Seas. Canada declared a five-year ban on new licensing in all Arctic waters, with a review based on climate and marine science at the end of that period.
The Canadian government is also revising its policy for the North. The Liberals said they are replacing the previous government's northern strategy with an "Arctic policy framework."
Former prime minister Stephen Harper's northern strategy put an emphasis on asserting Canadian sovereignty through the Canadian Rangers and addressing economic concerns through natural resource development.
There will be a specific component of the policy geared toward Inuit people.
Canada and the U.S. also announced they will start a process to identify low-impact shipping corridors. The process will include determining where vessels will not be allowed to sail and gauging what kind of infrastructure and emergency response systems will be needed for northern shipping routes.
In September, Obama became the first sitting president to travel north of the Arctic Circle. The joint Canada-U.S. statement covers oil and gas, community development and fisheries. (Andrew Harnik/Associated Press)
Both countries said they would regulate the development of fisheries in the Arctic. The U.S. said it will support existing commercial fishing closures in the Beaufort and Chukchi seas. Canada will work with northern and Indigenous communities to build Arctic fisheries based on scientific regulation.
N.W.T. premier 'concerned'
Northwest Territories Premier Bob McLeod said the federal government did not consult with his people ahead of today's announcement.
"We are concerned by the announcement and firmly believe northerners should be involved in making decisions that affect them and their economic future, and in this instance, they weren't," McLeod said.
"The North is an expensive place to live and there aren't a lot of options for people who need good jobs so they can provide for themselves and their families."
McLeod said his government is committed to environmentally sound growth, but that limiting fossil fuel development could be harmful to the sustainability of the northern way of life.
"I know the prime minister shares my concerns about generating growth for the North and was pleased that he committed to work with us immediately on a strategy for making lasting, positive change for the North."
'Unnecessary risk' for oil and gas, WWF says
Environmentalists are celebrating the drilling ban in a region that's among the most affected by climate change.
World Wildlife Fund-Canada president David Miller said Arctic conditions create an "unnecessary level of risk when it comes to oil and gas extraction."
"Today's announcement shows an impressive commitment to protect one of our most ecologically sensitive areas," Miller said in a statement.
Environmental Defence released a statement heaping "huge praise" on the Canadian and American governments. The organization said the decision to stop drilling will allow for the greatest chance of keeping the Arctic ecosystem and people healthy.
Political positioning
Michael Byers, a University of British Columbia professor who recently published a book called Who Owns the Arctic?, told The Canadian Press that the only surprise in the announcement is that it provides for a five-year review of the ban.
Byers said the move seems designed to show that Prime Minister Justin Trudeau is protecting the environment, despite a recent decision to sanction two oil pipelines — the Trans Mountain expansion and Line 3 replacement project.
"Closing the door to Arctic oil and gas helps to position himself on the climate change file by saying that there are limits in terms of the development of new oil and gas fields, therefore drawing a line in the sand from a climate change perspective," he said.
"There's no activity taking place in the Canadian Arctic right now, so saying no doesn't require anyone to stop."
The oil drilling rig Polar Pioneer, one of two drilling rigs Royal Dutch Shell planned to outfit for Arctic oil exploration, is shown in Seattle. (Elaine Thompson/Associated Press) |
Q:
CSS Selector for Table Row with X number of Cells
I'm trying to scrape some content off of a website and I am having trouble selecting the correct elements.
I'm using Nokogiri, and, as I know CSS best, I am trying to use it to select the data I want.
There is a big table with rows I do not want, but these can change; They are not always row 4, 5, 6, 10, 14 for example.
The only way I can tell if it's a row I want is if the row has TD tags in it.
What is the right CSS selector to do this?
# Search for nodes by css
doc.css('#mainContent p table tr').each do |td|
throw td
end
EDIT:
I'm trying to scrape boxrec.com/schedule.php. I want the rows for each match, but, it's a very large table with numerous rows which aren't the match. The first couple rows of each date section aren't needed, including every other line which has "bout subject to change....", and also spacing rows between days.
SOLUTION:
doc.xpath("//table[@align='center'][not(@id) and not(@class)]/tr").each do |trow|
#Try get the date
if trow.css('.show_left b').length == 1
match_date = trow.css('.show_left b').first.content
end
if trow.css('td a').length == 2 and trow.css('* > td').length > 10
first_boxer_td = trow.css('td:nth-child(5)').first
second_boxer_td = trow.css('td:nth-child(5)').first
match = {
:round => trow.css('td:nth-child(3)').first.content.to_i,
:weight => trow.css('td:nth-child(4)').first.content.to_s,
:first_boxer_name => first_boxer_td.css('a').first.content.to_s,
:first_boxer_link => first_boxer_td.css('a').first.attribute('href').to_s,
:second_boxer_name => second_boxer_td.css('a').first.content.to_s,
:second_boxer_link => second_boxer_td.css('a').first.attribute('href').to_s,
:date => Time.parse(match_date)
}
#:Weight => trow.css('td:nth-child(4)').to_s
#:BoxerA => trow.css('td:nth-child(5)').to_s
#:BoxerB => trow.css('td:nth-child(9)').to_s
myscrape.push(match)
end
end
A:
You won't be able to tell how many td elements a tr contains, but you can tell if it is empty or not:
doc.css('#mainContent p table tr:not(:empty)').each do |td|
throw td
end
|
Whatever you do, have fun doing it. If you don't, no one else is going to have fun for you.
Yes, everything that happens in movies is real.
The first part of this story comes from Anne, a friend of mine who lives out in L.A. She was attending a SAG [Screen Actors Guild] early screening of The Martian and Matt Damon was there to be part of an audience Q & A after the movie was over. Anne enjoyed the movie, but the part afterward… not so much.
The first person to ask a question was decked out in a dress like she was on a first date and piled enough compliments and adulation on Damon before she asked him anything that the upcoming question might as well have been, “Are you single?” Anne said it was actually a decent question, but the 2 1/2 minute Matt Damon lovefest before and afterward kinda tarnished the result.
The second question gave Anne a pretty good idea of how calm and relaxed some actors can be for the sake of their fans. Not only can they handle people who sound like they want to run up onto the stage during the Q & A session and do all sorts of unmentionable things to them in front of the audience, they handle questions after The Martian like, “Did that really happen?”
Yes.
I mean, no, the events in the movie didn’t happen, but the question did. Anne’s heart sank in her chest and she immediately became saddened for the Screen Actors Guild: there are people who present that kind of public image and have the SAG title attached to their names.
Again, he delivered a calm and relaxed response, which in this case was that it wasn’t a true story, but scientists are doing a lot of research about how to produce food, water, oxygen and whatnot so they could potentially send people out to Mars for a few months, etc. Uhhh… in case you didn’t know The Martian is about someone being on Mars, I guess I should have added a spoiler alert before this paragraph.
Suffice it to say that actors have to deal with a lot of dumb questions, but it inspired a group of us to come up with one for the next Q & A session that would include Matt Damon. For those of you who don’t know, he’s currently working on a fifth Jason Bourne movie that’s supposed to be released in 2016.
The question we came up with wasn’t, “Did the stuff in that movie really happen?” That question should be saved for a silly person who wants to indulge in another lovefest. Nope, we decided she should get the microphone and ask Matt Damon, “How many people have you killed with your bare hands?” Mic drop, walk away. Q & A session complete. |
How much influence do medical publications have on your doctor? A great deal, says new SLU research
ST. LOUIS – New research by Saint Louis University in today's Journal of the American Medical Association asks two intriguing questions: How much impact do articles in prominent medical journals really have on how doctors treat patients, and how fast does that impact affect clinical practice?
The answers? Quite a bit, and very quickly – if the news is negative.
Researchers from the Saint Louis University Center for Outcomes Research studied nearly 400,000 hospital admissions of heart failure patients before and after two articles appeared in Circulation and JAMA in early 2005 suggesting nesiritide, a popular medication for acute decompensated heart failure, had an increased risk of kidney failure and death.
After the articles were published, nesiritide use in heart failure patients fell from a peak of 16.6 percent in March 2005 to only 5.6 percent in December 2005. The decreases were greatest in the elderly, reflecting heightened concerns about risks in this population.
"The results were notable – and to a large extent unexpected," says Paul J. Hauptman, M.D., cardiologist at Saint Louis University School of Medicine and lead author. "Not only did doctors appear to change practice when confronted with a potential safety problem, but they also did so far more rapidly than we expected."
Hauptman says this is remarkable, considering that earlier studies have shown that the opposite is true.
"When medications are shown to improve survival, it takes doctors longer to adopt them into practice," he says.
Likening it to the effect articles in Vogue have on the fashion industry, co-author Mark Schnitzler, Ph.D., associate professor of medicine at Saint Louis University, says articles in major medical journals have tremendous influence over physicians.
"Most doctors, academic or not, read JAMA and the New England Journal of Medicine," Schnitzler says. "Most are probably just scanning the articles or monitoring media coverage of the articles, but they believe they can trust the information being presented. Now we know that the information does have a very real effect on the doctor-patient relationship."
Researchers already know a good deal about why – and how quickly – doctors begin using new drugs to treat their patients, Hauptman says.
"But much less is known about the factors that lead to a decrease in the use of a particular drug," he says.
Using a database of 491 acute care hospitals in the United States, the team studied 385,627 heart failure patient records in: the four months preceding the two articles and the eight months following; the same time periods in 2004 for comparison; and the eight months preceding the launch of nesiritide in 2001.
The researchers also hypothesized that doctors would increasingly prescribe competing drugs to treat heart failure. In fact, the use of most drugs for the condition did not increase. However, among patients prescribed intravenous drugs to treat heart failure (aside from diuretics), use of inotropes increased, which Hauptman says is noteworthy because there is extensive research on the potential risk of death with this class of drug.
Their findings, say team members, have far-reaching implications.
"With an increasing focus on drug safety, we need to recognize that the publication of research that calls into question the safety of a drug can have a great impact on physicians, and, as a consequence, on patients and drug companies," Hauptman says. "Whether these effects would occur with other drugs or devices remains to be seen. In the meantime, 'keeping up with the latest medical research' takes on a whole new meaning."
###
Other investigators involved in the study were Thomas Burroughs, Ph.D., director of SLUCOR, and Jason Swindle, MPH.
Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first M.D. degree west of the Mississippi River. Saint Louis University School of Medicine is a pioneer in geriatric medicine, organ transplantation, chronic disease prevention, cardiovascular disease, neurosciences and vaccine research, among others.
Last reviewed:
By John M. Grohol, Psy.D. on
21 Feb 2009
Published on PsychCentral.com. All rights reserved. |
Q:
Can't display icons in tab navigation wix react-native-navigation
I can't get the tabs icon to render in iOS simulator.
Navigation.startTabBasedApp({
tabs: [
{
label: 'Home',
screen: 'Home', // this is a registered name for a screen
icon: require('img_assets/icon_message.png'),
iconInsets: { top: 0, left: 0, bottom: 0, right: 0 },
visible: true,
//selectedIcon: require('../img/one_selected.png'), // iOS only
title: 'Homepage'
},
{
label: 'Second',
screen: 'Second',
icon: js.Lib.require('img_assets/icon_cloud/cloud.png'),
iconInsets: { top: 0, left: 0, bottom: 0, right: 0 },
visible: true,
//selectedIcon: require('../img/two_selected.png'), // iOS only
title: 'Screen Two'
}
],
tabsStyle: {
tabBarButtonColor: '#FF0000',
tabBarSelectedButtonColor: '#00adf5'
},
appStyle: {
tabBarButtonColor: '#000000', // BottomTabs unselected button color
tabBarSelectedButtonColor: '#00adf5', // BottomTabs selected button color
}
});
in package.json
"dependencies" : { ...
"img_assets": "file:assets/"
Screenshot:
Environment
React Native Environment Info:
System:
OS: macOS High Sierra 10.13.4
CPU: x64 Intel(R) Core(TM) i5 CPU 750 @ 2.67GHz
Memory: 32.35 MB / 12.00 GB
Shell: 3.2.57 - /bin/bash
Binaries:
Node: 8.12.0 - /usr/local/bin/node
Yarn: 1.9.4 - /usr/local/bin/yarn
npm: 6.4.1 - /usr/local/bin/npm
Watchman: 4.9.0 - /usr/local/bin/watchman
SDKs:
iOS SDK:
Platforms: iOS 11.4, macOS 10.13, tvOS 11.4, watchOS 4.3
IDEs:
Android Studio: 3.1 AI-173.4907809
Xcode: 9.4.1/9F2000 - /usr/bin/xcodebuild
npmPackages:
react: 16.5.0 => 16.5.0
react-native: 0.57.0 => 0.57.0
npmGlobalPackages:
create-react-native-app: 1.0.0
react-native-cli: 2.0.1
Do you have any insight of what could happen?
I'm not having an error anymore (used to have some) so I guess the images are correctly linked/loading now. But can't see any at screen.
A:
The problem was with images themselves AND the fact that react-native-navigation applies "by default" a color tint.
|
#pragma once
#include "OpenDatabaseDialog.h"
class DecryptDatabaseDialog7 : public Dialog
{
private:
OpenDatabaseStruct &openDatabaseStruct;
void selectDatabaseFile();
void selectKeyFile();
void clickOk(WPARAM wParam);
protected:
virtual INT_PTR callback(HWND dialog, UINT message, WPARAM wParam, LPARAM lParam);
public:
DecryptDatabaseDialog7(HWND parent, OpenDatabaseStruct &openDatabaseStruct);
~DecryptDatabaseDialog7();
const std::string &getFilename();
const std::string &getKeyFilename();
};
|
Q:
Bean null after sign up user?
I have a bean UserControl with SessionScope, after the user register at the system, he/she would try to log in on the system, right ?
The same bean is used for it, but after the try log in once (with a wrong passwod for instance) on the second try, appears an exception that my bean is null, why ?
I use the same composition at register form and login form:
<!DOCTYPE html>
<ui:composition
xmlns="http://www.w3.org/1999/xhtml"
xmlns:f="http://java.sun.com/jsf/core"
xmlns:h="http://java.sun.com/jsf/html"
xmlns:ui="http://java.sun.com/jsf/facelets">
E-Mail:<h:message id="m_email" for="email" styleClass="red" /><br/>
<h:inputText id="email" value="#{userC.user.email}" maxlength="45" validatorMessage="e-mail inválido" >
<f:validateLength minimum="6" maximum="45" />
<f:ajax event="blur" render="m_email" />
</h:inputText>
<br/>
</ui:composition>
At the first time work but on the second, don't.
Given me this exception:
/resources/jsf/composition/body/user/form/email.xhtml @9,108 value="#{userC.user.email}": Target Unreachable, 'null' returned null
This is my bean, UserControl:
@ManagedBean(name="userC")
@SessionScoped
public class UserControl implements Serializable{
private static final long serialVersionUID = 7708365499838642904L;
@EJB UserEAO userEAO;
@EJB AddressEAO addressEAO;
private User user;
private Message message;
/*
* Variable
*/
private boolean logged;
public UserControl(){
user = new User();
user.setAddressCity(new AddressCity());
user.setAddressState(new AddressState());
user.setAddressCountry(new AddressCountry());
logged = false;
}
.. methods
}
Is wrong initiate my objects in the constructor ?
update
Full code of UserControl:
package com.hi.mvc.controller;
import java.io.IOException;
import java.io.Serializable;
import java.text.DateFormat;
import java.text.ParseException;
import java.text.SimpleDateFormat;
import java.util.Date;
import javax.ejb.EJB;
import javax.faces.application.FacesMessage;
import javax.faces.bean.ManagedBean;
import javax.faces.bean.SessionScoped;
import javax.faces.context.ExternalContext;
import javax.faces.context.FacesContext;
import com.hi.mvc.eao.AddressEAO;
import com.hi.mvc.eao.UserEAO;
import com.hi.mvc.model.AddressCity;
import com.hi.mvc.model.AddressCountry;
import com.hi.mvc.model.AddressState;
import com.hi.mvc.model.User;
import com.hi.utility.Crypto;
import com.hi.utility.Email;
import com.hi.utility.Message;
@ManagedBean(name="userC")
@SessionScoped
public class UserControl implements Serializable{
private static final long serialVersionUID = 7708365499838642904L;
@EJB UserEAO userEAO;
@EJB AddressEAO addressEAO;
private User user;
private Message message;
/*
* Variable
*/
private boolean logged;
public UserControl(){
user = new User();
user.setAddressCity(new AddressCity());
user.setAddressState(new AddressState());
user.setAddressCountry(new AddressCountry());
logged = false;
}
/*
* CRUD
*/
public String register(){
if (userEAO.find(user.getEmail()) == null){
defineUser();
message = userEAO.create(user);
//sending user email confirmation
if (message.getCode() == 0) {
message = new Message(1);
message.setEmail(user.getEmail());
sendConfirmationEmail(user);
return "/pages/system/message.xhtml?faces-redirect=true";
}else
//user already registered and trying to register again
message = new Message(-1002);
}
addMessage();
return null;
}
public String update() {
message = userEAO.update(user);
this.addMessage();
return null;
}
public String delete(){
message = userEAO.delete(user);
if (message.getCode() >= 0)
try {
ExternalContext ec = FacesContext.getCurrentInstance().getExternalContext();
ec.invalidateSession();
message = new Message(3001);
addMessage();
ec.redirect(ec.getRequestContextPath() + "/pages/system/message.xhtml");
} catch (IOException e) {
// TODO Auto-generated catch block
e.printStackTrace();
}
addMessage();
return null;
}
/*
* Log in/off
*/
public String login(){
String password = user.getPassword();
user = userEAO.find(user.getEmail());
// if user was found
if ( user != null ){
if ( user.getEmailConfirmed()){
// with facebook registration, password is empty, so we avoid login empty and check the password
if ( !user.getPassword().isEmpty() && Crypto.check(password, user.getPassword())){
//user = addressEAO.findByUser(user.getId());
logged = true;
return "/index.xhtml?faces-redirect=true";
}else
message = new Message(-2000);
}else
message = new Message(-1003);
}else
message = new Message(-2000);
addMessage();
return null;
}
public void logout(){
try {
ExternalContext ec = FacesContext.getCurrentInstance().getExternalContext();
ec.invalidateSession();
ec.redirect(ec.getRequestContextPath() + "/index.xhtml");
} catch (IOException e) {
// TODO Auto-generated catch block
e.printStackTrace();
}
}
/*
* Functions
*/
public void defineUser(){
encryptPassword(user);
user.setMemberSince(new Date());
user.setAcceptanceRate(0);
user.setResponseRate(0);
// user do not confirm email yet
user.setEmailConfirmed(false);
// set address to be empty
user.getAddressCity().setCity(" ");
user.getAddressState().setState(" ");
user.getAddressCountry().setCode(" ");
defineAddress();
}
public void defineAddress(){
AddressCity addressCity = addressEAO.findCity(user.getAddressCity().getCity());
if (addressCity == null){
addressCity = new AddressCity();
addressCity.setCity(user.getAddressCity().getCity());
addressEAO.createCity(addressCity);
}
user.setAddressCity(addressCity);
AddressState addressState = addressEAO.findState(user.getAddressState().getState());
if (addressState == null){
addressState = new AddressState();
addressState.setState(user.getAddressState().getState());
addressEAO.createState(addressState);
}
user.setAddressState(addressState);
AddressCountry addressCountry = addressEAO.findCountry(user.getAddressCountry().getCode());
if (addressCountry == null){
addressCountry = new AddressCountry();
addressCountry.setCode(user.getAddressCountry().getCountry());
addressEAO.createCountry(addressCountry);
}
user.setAddressCountry(addressCountry);
}
/*
* Date
*/
public Date convertDate(String date){
try {
DateFormat formatter = new SimpleDateFormat("MM/dd/yy");
return (Date)formatter.parse(date);
} catch (ParseException e) {
// TODO Auto-generated catch block
e.printStackTrace();
}
return null;
}
/*
* E-Mail
*/
public void sendConfirmationEmail(User u){
Email email = new Email();
email.setUser(u);
email.setSubject("Hotel Informal - Por favor, confirme seu endereço de email");
email.simpleEmail();
}
public void sendWelcomeEmail(User u){
Email email = new Email();
email.setUser(u);
email.setSubject("Hotel Informal - Olá, seja bem-vindo(a)");
email.simpleEmail();
}
public String resendEmailConfirmation(){
sendConfirmationEmail(user);
message = new Message(2);
message.setEmail(this.user.getEmail());
return "/pages/system/message.xhtml?faces-redirect=true";
}
/*
* Password
*/
public void encryptPassword(User u) {
if (u.getPassword() != null){
u.setPassword(Crypto.encrypt(u.getPassword()));
}
}
public String changePassword(){
encryptPassword(user);
message = userEAO.update(user);
if (message.getCode() >= 0)
message = new Message(2002);
addMessage();
return null;
}
public Message checkPassword(User user) {
if (user == null)
return new Message(-3000);
if (Crypto.check(user.getPassword(), user.getPassword())) {
return new Message(1);
} else
return new Message(-2000);
}
public String forgotPassword(){
user = userEAO.find(user.getEmail());
if (user != null){
Email email = new Email();
email.setUser(user);
email.setSubject("Hotel Informal - Redefinir senha");
email.simpleEmail();
message = new Message(6);
message.setEmail(user.getEmail());
}else
message = new Message(-1004);
addMessage();
return "/pages/system/message.xhtml?faces-redirect=true";
}
public String resetPassword(){
encryptPassword(user);
userEAO.update(user);
Email email = new Email();
email.setUser(user);
email.setSubject("Hotel Informal - Senha redefinida");
email.simpleEmail();
message.setEmail(user.getEmail());
message = new Message(2001);
addMessage();
return "/pages/system/message.xhtml?faces-redirect=true";
}
private void addMessage(){
FacesMessage fMessage = new FacesMessage(message.getMessage());
FacesContext.getCurrentInstance().addMessage(null, fMessage);
}
// get's & set's
public Message getMessage() {
return message;
}
public void setMessage(Message message) {
this.message = message;
}
public User getUser() {
return user;
}
public void setUser(User user) {
this.user = user;
}
public boolean isLogged() {
return logged;
}
public void setLogged(boolean logged) {
this.logged = logged;
}
}
A:
Following the suggestions of maple_shaft and kolossun wasn't enough to solve my problem, but following this suggestion, to check if the user is null in the public User getUser() method was.
@PostConstruct
public void init(){
if (user == null){
user = new User();
logged = false;
}
if (user != null && user.getAddressCity() == null)
user.setAddressCity(new AddressCity());
if (user != null && user.getAddressState() == null)
user.setAddressState(new AddressState());
if (user != null && user.getAddressCountry() == null)
user.setAddressCountry(new AddressCountry());
}
And :
public User getUser() {
init();
return user;
}
This way I ensure that the object user and the others classes are always initialized.
Still I don't understand why doing the null check in @PostConstruct wasn't enough, it keeps given me the same error.
|
Q:
Why are all the Sequelize example models instantiated with Model(sequelize, Sequelize)?
Take a look at the models/blog.js definition in this Sequelize tutorial.
module.exports = (sequelize, type) => {
return sequelize.define('blog', {
id: {
type: type.INTEGER,
primaryKey: true,
autoIncrement: true
},
text: type.STRING
})
}
It gets called like this:
const BlogModel = require('./models/blog');
const sequelize = new Sequelize('codementor', 'root', 'root', {...});
const Blog = BlogModel(sequelize, Sequelize);
I have scoured many more Sequelize example and found the Model(sequelize, Sequelize) "pattern" in probably at least 90% of them. Almost as if all of them derive directly or indirectly from some really poor code example, because...
This looks really ugly to me. There are two variables that are only distinguished by case. One of the is the Sequelize library, the other something like a session or connection (not sure which term Sequelize uses). Having upper-case variables is I think a coding guideline violation. Next, a library reference gets passed into another file, which should be completely unnecessary in Node because requires modules get cached on the first load. So why not just reference Sequelize in the model files directly and only pass the sequelize object?
Does someone see any good reason to do it this way? An IMO much cleaner way to do it is described in this SO post. Kudos to the answerer. I'm just wondering if I'm missing something obvious here, that I really should do it this way, or if I'm free to write some cleaner code?
A:
That is really ugly. What I do is I create a db in it's own file and export it.
const db = new Sequelize(
process.env.DATABASE_URL || `postgres://localhost:5432/${databaseName}`,
)
module.exports = db
In the blog.js file I'll import it and do something like this:
const Sequelize = require('sequelize')
const db = require('../db')
const blog = db.define('blog', {
your_field_name_here: {
type: your_sequelize_type_here
},
... and so on
})
module.exports = blog
Not entirely sure why they do it that way, but I find defining models this way much cleaner and it should achieve what you're trying to achieve. There are some out of date things the Sequelize docs, so it wouldn't surprise me if that's how things used to be.
|
John Tsunis, chairman and CEO of Gold Coast Bank, on Oct. 15, 2015. He wants to form a Long Island Greek-American Chamber of Commerce. Photo Credit: Ed Betz
Local business and civic leaders met last week to plan the launch of the Long Island Greek-American Chamber of Commerce, which aims to foster ties among entrepreneurs and professionals in the region.
The founders gathered at the Holiday Inn Express Stony Brook on Thursday to discuss leadership posts. The breakfast meeting drew about 85 people, and an announcement is expected within weeks about who will head the new group, a spokesman said Monday.
Those forming the association include doctors, lawyers, bankers and owners of local businesses -- many, but not all of them, of Greek descent, said John C. Tsunis, chairman and chief executive of Islandia-based Gold Coast bank, who is spearheading the effort.
"I'm trying to set up a chamber where people are connected with each other, where people can trade services and information," Tsunis said.
Long Island is home to local chambers of commerce from Floral Park to Montauk, as well as associations fostering ties among Hispanic and African-American entrepreneurs, among others.
Such groups can keep members informed about business opportunities, help small business owners manage their finances and connect entrepreneurs with each other, said Phil Andrews, president of the Freeport-based Long Island African American Chamber of Commerce.
"If you don't have a business organization, sometimes the resources don't come to the community, the technical assistance -- things like businesses being able to do a cash flow statement, having a proper business plan," Andrews said. "A lot of businesses start and they're good at what they do, but they have problems when they begin to grow." |
Difference between revisions of "SMILA/Documentation/Search"
(New page: SMILA Search == This page describes the search service and related parts of SMILA. This includes the query and result helpers, the processing of search requests in BPEL workflows, and the...)
Let's start at the top: If you have installed SMILA and created an index by starting a crawler you can now use you web browser to go to [http://localhost:8080/SMILA/search] to search the index:
+
Let's start at the top: If you have installed SMILA and created an index by starting a crawler you can now use you web browser to go to [http://localhost:8080/SMILA/search http://localhost:8080/SMILA/search] to search the index:
What happens behind the scenes when you enter a query string and submit the form is that a servlet creates a SMILA record from the HTTP parameters, uses the search service to execute a BPEL workflow on this record, receives an enriched version of the query record and a list of result records in XML form and uses an XSLT stylesheet to create a result HTML page.
What happens behind the scenes when you enter a query string and submit the form is that a servlet creates a SMILA record from the HTTP parameters, uses the search service to execute a BPEL workflow on this record, receives an enriched version of the query record and a list of result records in XML form and uses an XSLT stylesheet to create a result HTML page.
Line 13:
Line 13:
Using the [http://localhost:8080/SMILA/search?style=SMILASearchAdvanced Advanced] link at the top you can switch to more detailed search page:
Using the [http://localhost:8080/SMILA/search?style=SMILASearchAdvanced Advanced] link at the top you can switch to more detailed search page:
This page allows you to enter a more specific query. In case you want to use the default search servlet for your own search page you should use the XSLT files that create these two pages as a reference when trying to design your own search page.
This page allows you to enter a more specific query. In case you want to use the default search servlet for your own search page you should use the XSLT files that create these two pages as a reference when trying to design your own search page.
−
=== Search Processing ===
=== Search Processing ===
Revision as of 08:33, 6 April 2009
SMILA Search ==
This page describes the search service and related parts of SMILA. This includes the query and result helpers, the processing of search requests in BPEL workflows, and the sample servlet used to create a simple search Web GUI.
Introduction
Let's start at the top: If you have installed SMILA and created an index by starting a crawler you can now use you web browser to go to http://localhost:8080/SMILA/search to search the index:
SMILA's sample search page
What happens behind the scenes when you enter a query string and submit the form is that a servlet creates a SMILA record from the HTTP parameters, uses the search service to execute a BPEL workflow on this record, receives an enriched version of the query record and a list of result records in XML form and uses an XSLT stylesheet to create a result HTML page.
Using the Advanced link at the top you can switch to more detailed search page:
SMILA's advanced sample search page
This page allows you to enter a more specific query. In case you want to use the default search servlet for your own search page you should use the XSLT files that create these two pages as a reference when trying to design your own search page.
Search Processing
Having seen the tip of the iceberg, we dive down to the very bottom of SMILA search: the actual processing of search requests in SMILA BPEL pipelines. We assume that you are accustomed to the basic SMILA workflow processing features used in indexing workflows. You may want to refer to SMILA/Documentation/BPEL_Workflow_Processor for details.
Search Pipelines
Search workflows (or pipelines) are very similar to indexing pipelines, but there are a few extensions. The variables in indexing pipelines represent just a simple list of records. This is not sufficient for search pipelines where we need to distinguish between the single record representing the user query (the "query record") and the current list of result records (the "search result"). This results in a few general differences between the BPEL files of indexing and search pipelines:
the partner link of the pipeline must be of type "proc:SearchProcessorPartnerLinkType":
the input and output variables of the pipeline itself and of pipelet/service invocations must have the message type "proc:SearchProcessorMessage". This message has only a single part named "records" which can contain a single record (the query record) and a record list (the result records). Refer to org.eclipse.smila.processing.bpel/xml/processor.wsdl for the details of the schema definition.
Apart from this, pipelet/service invocations look the same as in indexing pipelines. See SMILA.application/configuration/org.eclipse.smila.processing.bpel/pipelines/SearchPipeline.bpel for a complete example search pipeline (the one used in the above sample).
SimplePipelets/ProcessingServices in Search pipelines
Recall that the signature of the invocation method of SimplePipelets/ProcessingServices is
This means when used in search pipelines they cannot process a complete message variable. Therefore the engine selects one part of the message when invoking a "simple" pipeline element:
if there is not yet a result record list in the message (not even an empty one) the pipelet is called with the query record ID and the output message contains only a single query record ID, too.
else it is called with the result record list and the result becomes the record list of the output variable. The query record ID is just copied to the result variable.
The rationale behind this is that in a search pipeline first some pipelets may be needed to prepare the query object (enrich the query, set some defaults, etc.), then follows the actual search, which takes the query as input and produces a list of results (thus adds the result record list to the variable) and then additional pipelets may be needed to manipulate the result further. Using the distinction described above makes it possible to use the same pipelet implementation for query and result records, just depending on their position in the pipeline.
SearchPipelets/SearchProcessingServices
For some operations in search pipelines this invocation pattern is not sufficient, the most prominent being the actual search implementation itself: It needs the query record as input and produces a result record list. But there may be other pipelets after the actual search that need to compare query and result records and therefore need access to both kinds of record. To support this, two new interfaces have been defined:
org.eclipse.smila.processing.SearchPipelet
org.eclipse.smila.processing.SearchProcessingService
Concerning life cycle and configuration they are identical to standard Simple Pipelets and Processing Services: Pipelets are created and configured by the BPEL engine and must be declared in teh MANIFEST.MF of the providing bundle. ProcessingServices are started independently from the BPEL engine as OSGi services (though for different service interfaces). The enhancement provided by the search pipelets/service is a new invocation method:
where SearchMessage consists of a query record ID and a record ID list.
Search Service API
The actual Search API is quite simple: SMILA registeres an OSGi service with the interface org.eclipse.smila.search.api.SearchService. It provides a few methods that take a
SMILA query record and the name of a search workflow as input, execute the workflow on the record and return the result in different formats:
SearchResult search(String workflowName, Record query) throws ProcessingException: this is the basic method of the search service, that returns the result records as SMILA data structures. The other methods call this method for the actual search execution, too, and just convert the result.
org.w3c.dom.Document searchAsXml(String workflowName, Record query) throws ProcessingException: return the search result as a XML DOM document. See below for the schema of the result.
String searchAsXmlString(String workflowName, Record query) throws ProcessingException: return the search result as an XML string. See below for the schema of the result.
The schema of XML search results is basically as follows (target namespace is http://www.eclipse.org/smila/search, see org.eclipse.smila.search.api/xml/search.xsd for the full definition):
You can view the result XML by using the sample SMILA search page [1] and selecting the "Show XML result" checkbox before submitting the query.
The content of the query record basically depends a lot on the used search services. E.g. using the LuceneSearchService, you can set attribute values to search in the index fields to which these attributes have been mapped during indexing (refer to the Lucene integration documentation for details). Other search parameters are attached to the query record as annotations. However, the Search API is also a recommendation where to put some basic, commonly used search parameters, which all index integrations should honor (of course they may quite specify extensions that are not covered by the generic Search API). The following sections describes these recommendations.
Query Parameters
Parameters are stored in a single place in the query record and used to describe relatively simple query properties: The query record has a single annotation named "parameters", which can contain:
single valued parameters: named values of the annotation
multi valued parameters: subannotation with the parameter name and the values as its anon-values list.
map valued parameters: subannotations with named values
The Search API defines also the names, allowed values and default values for a set of commonly used parameters. All implementations should use these properties if possible, i.e. they should not introduce additioal parameters for the same purpose, but it may be possible that certain parameters are not supported because it is not feasible with the underlying technology. For some parameters we also define default values. All parameters are single values if not specified differently.
query: the search string. The index implementor can define a syntax to describe complex search criteria in a single string, SMILA does currently not define an own query syntax. The index implementor might or might not be able to merge this query string with search criteria described by attribute values/annotations of the query record.
resultSize: number of records to return to the search client, default value is 10.
resultOffset: number or top results to skip, default value is 0. Use this parameter to implement result list paging: If resultSize=10, the "next page" queries can be identical to the initial query, but with resultOffset=10, 20, ....
threshold: minimal relevance score that a result must have, default is 0.0.
language: language of the query, no default value. There could be language specific pipelets/services that need to know in which language the user is expressing his query to work correctly.
indexName: some index services (like our LuceneIndexService) can manage multiple indexes at once, then they can use this parameter to select the index to search with this request. However, they always should have a default index name configured somehow so that a request succeeds without having this parameter set.
resultAttributes: multi-valued parameter, describing the names of attributes that should be added to result records by the search engine. This list should only contain the attributes needed by pipelets after the search for processing or by the search page for displaying the results, including too many attributes will always decrease performance. Omitting this parameter should result in getting all available attributes.
orderBy: map valued parameter with named values "attribute" (any string) and "mode" ("ASC"/"DESC") specifying that the search result should be be sorted by the named attributes in the given direction. Omitting this parameter should result in search result sorted by relevance (score, similarity, ranking, ....). Multiple orderBy annotations can be added and should be evaluated in the order of appearance.
Query Attribute Annotations
Additional annotations can be added to attributes for which they describe refinements of the search. They usually contain only named values and anonymous values.
Filters: Filters describe hard restrictions on the values of result record attributes that must be matched for a record to be included in a result (in opposite to attribute values which may describe only soft criteria). Advanced search engines might even allow to add multiple filter annotations to a single attribute.
type: "ENUMERATION"/"RANGE": Specifies if the filter is described by an explicit enumeration of allowed/forbidden values or by giving the lower and/or upper bound. For enumeration filters, the actual filter values are added as anonymous values to the filter annotation. For range filters, see below.
mode: "ALL"/"ANY"/"ONLY"/"NONE": Specify whether an allowed object must have all, any, only or none of the filter values to match the filter.
min/max: Specify the lower and/or upper bound of a range filter.
Ranking: Contains properties that modify the ranking or relevance score of results by manipulating the relevance valuation for a single attribute or for the complete record (if attached to the record itself, not an attribute). Two property names are predefined, but search engine integrations may include additional names:
name: if the engine knows a number of different named ways or algorithms to compute the relevance this property can be used to select a different one than the default
boost: changes the weight of this attribute when the local relevance is accumulated into a global one.
Result Annotations
Annotations may not only be attached to the query record, but to the records in the search result, too. There are even additional annotations attached to the query object to describe result properties that do not refer to a single result record, but to the complete search result.
result statistics: After the search the query record contains an annotation named "result" that currently contains these named values
runtime: runtime for the invoked pipeline, in milliseconds
totalHits: number of possible results for this query, i.e. all objects from an index that have a relevance score greater than the specified threshold (or zero).
indexSize: complete number of objects in the searched index.
Score: Each result record should have a "result" annotation, too, giving at least the ranking score calculated by the search engine as named value "relevance" as a double value (usually 1 means: perfect match).
Highlighting: TODO
Facets: TODO
Terms: TODO
Helper Classes
There are some classes that help a client to create query records with their annotations and to read out result records and their annotation. You can find them in package org.eclipse.smila.search.api.helper:
QueryBuilder: helper class for building queries and sending the query to search service. Returns a result in the form of the next class:
ResultAccessor: wrapper for the complete search result. Does not do much on its own, but basically creates instances of the following classes to access the records of the result.
QueryRecordAccessor: Defines methods for accessing literals and annotations of the enriched query that is part of the search result.
ResultRecordAccessor: Defines methods for reading literals and annotations of search result records.
See the source code or javadocs for more details of the provided methods.
Servlet
Additionally to this "search backend", SMILA contains a simple servlet that creates a query record from HTTP parameters and displays the result as an HTML page by converting the XML search result using an XSLT stylesheet. This servlet is intended for quick demos, not for productive use. It is usually deployed in the Tomcat instance that comes with SMILA at "/SMILA/search". On first invocation it currently creates a quite empty query record (it sets some default parameters like resultSize etc) and processes it with the default pipeline "SearchPipeline". The pipeline should be able to process such a query and return an empty result list, not an error. The XML serialization of this this empty result is then transformed using the default stylesheet ("SMILASearchDefault") to present an initial search page.
XSLT Stylehsheets for SMILA search and result pages
The stylesheets are loaded from the configuration directory "org.eclipse.smila.search.servlet" and select using the HTTP parameter "style". The value of this parameter must be the stylesheet filename without suffix, the suffix must bei .xsl. The servlet currently uses the hardcoded default name "SMILASearchDefault" if no other value is set.
In the default application, three stylesheets are avaiable:
SMILASearchDefault: the default search page. Use this as a reference for how to describe simple queries and to present result lists, including paging through bigger results.
SMILASearchAdvanced: same layout for the result list, but demostrates how to create more complex query records with attribute values and filters.
SMILASearchTest: primitive layout, no paging, but demonstrates the setting of even more query features.
In the following we will describe how to set query record features using the servlet. Please have a look at those sample stylesheets for complete examples of how to apply them, as we will not present something like a full tutorial here (-;
Setting parameters
To set a parameter, just use the parameter name as the HTTP parameter name. All values for this HTTP parameter are added to the "parameters" annotation of the query record. E.g., to set the "resultSize" parameter to 7 using an HTML hidden input field, use:
<inputtype="hidden"name="resultSize"value="7"/>
See below for naming rules for the HTTP parameter names to set attribute literals and annotations. Note that you cannot set a parameter with a name that matches one of these rules.
Setting attributes
You can add literal string values to attributes using "A.<AttributeName>" as the HTTP parameter name. E.g., to set a value from a HTML text input field as an literal in attribute "Title", use:
<inputtype="text"name="A.Title"/>
Setting other annotations
To set a named value in the ranking annotation for the complete record or an attribute, use "R.<ValueName>[.<AttributeName>]". You are not limited to the predefined ranking value names "name" and "boost". E.g., the following input field sets add a named value "Operator=OR" to attribute "Content":
<inputtype="hidden"name="R.Operator.Content"value="OR"/>
To create a filter for an attribute, use HTTP params:
"F.<AttributeName>" to set the filter mode ("ALL", "ANY", "ONLY", "NONE")
"Fval.<AttributeName>" to add filter values to an enumeration filter.
"Fmin.<AttributeName>" and "Fmax.<AttributeName>" to set the lower/upper bounds of a range filter.
If both "Fval" and "Fmin/Fmax" paramaters are set, the servlet will create both an enumeration filter and a range filter with the same filter mode. It depends on the used search engine integration what happens in this case. E.g.
to set a filter for attribute "MimeType" restricting the result to HTML documents, use:
<inputtype="hidden"name="Fval.MimeType"value="text/html"/>
to set a filter for attribute "FileSize" restricting the result to document sizes between 1000 and 10000 bytes, use:
To set named values in other attribute annotations, use "A.<AttributeName>.(<AnnotationName>.)+<ValueName>". Note that this does not work for attribute and annotation names containing "." characters. E.g., the following snippet create an annotation "highlight" on attribute "Concent", with a sub-annotation "HighlightingTransformer" and a named value "name=Sentence": |
Brazil boosts security for Confederations Cup
On Sunday night Brazil is set to square off against Spain for the Confederations Cup title in front of an estimated 77,000 fans at the famed Maracana stadium.
But when the match starts, the action might be just as hot outside the stadium as whatever would be happening on the pitch.
In response to the most widespread social unrest ever in Brazil, the police have mounted the largest and most complicated security operation the country has ever attempted for a football match.
The Rio police will have 6,000 officers on hand, six times more than for the first Confederations Cup match in Rio just two weeks ago between Mexico and Italy.
Added to that, there will be roughly 600 members of the Ministry of Justice National Force officers, plus an estimated 4,000 other federal security agents, raising the total to almost 11,000 security force. And that is just outside the stadium.
Inside Maracana, security will be handled by a team of 1,300 private security guards (250 more than normal) under auspices of the local organising committee and FIFA.
The 1989 World Cup qualifier in Rio between Brazil and Chile had 2,000 local police, and was until now the largest security operation for a football match inside Brazil. Sunday’s match will be three times larger just in the number of local police deployed.
Despite the fact that the vast majority of the protesters are peaceful, and specially go out of their way to avoid conflict or violence, police say the wall of security will be necessary to ensure ticketed fans, vendors, delegations and FIFA officials can get to the stadium while also maintaining a strict security bubble around the stadium in accordance with FIFA demands and contractual obligations between Brazil and the football body.
Acts of vandalism
Rio police Col. Frederico Caldas told me on Saturday that as the protests increased in intensity at Confederations Cup host cities in the past two weeks, the plans changed for security at Maracana.
"In our initial planning we were going to use 1,000 police officers at Maracana, that is what we had for the Brazil and England friendly," he told me from his office at the main police headquarters in Rio.
"The idea was to repeat this throughout the Confederations Cup tournament, but because of the protests and the increased possibility that protesters will try to block access to the stadium, we have increased security considerably."
Caldas has no idea what to expect in terms of crowds on Sunday, but said they are preparing for hundreds of thousands. He said acts of vandalism by small groups of protesters will not be tolerated.
"The police need to be concerned with providing security to the people on the perimeter of the stadium including the protesters and guaranteeing our safety," he said.
"Because what we have seen in protests the past couple weeks in several host cities is repression and police violence against protesters and even journalists."
A journalism watchdog group in Brazil says that more than 50 journalists have been injured during street protests in the country since the uprising started, many claim to have been targeted by riot police.
Everybody is hoping Sunday is peaceful and both the football and the protests go off without violence.
But just in case, Col. Caldas told me they have stocked up on extra tear gas to replenish a supply that was running low. |
Intra- and inter-modal effects of prior stimulation on cardiac responsiveness to repeated stimulation in the human newborn.
The effect of prior equivalent auditory and somesthetic input on cardiac acceleration responses to repeated auditory and somesthetic stimulation was studied in 56 healthy 2- or 3-day-old infants. Responsiveness to initial presentation of the reiterative auditory stimulus was significantly greater than to the reiterative somesthetic stimulus regardless of the modality stimulated during the preceding series. In contrast the course of response decrement to subsequent repeated presentations of both stimuli was significantly more rapid when the reiterative and prior stimuli were in different modalities (inter-modal) than when they were in the same modality (intra-modal). The findings demonstrate a modality difference in effect of anticedent input on initial responiveness and a greater efficacy of inter- than of intra-modal auditory and somesthetic stimulation for the habituation of neonatal cardiac responses to repeated stimulation. |
Applying powders in a melt state onto surfaces--in particular metal surfaces--represents a well known method. So e.g. the HU-PS 159 923 discloses a method of this type for applying and preparing a coating. In course of said method the flame required for melting is produced by using a mixture of acetylene and oxygen or acetylene and air. Powder--e.g. aluminium powder--is blown by means of pressurized air along a plane between two slabshaped flames tending to each other and melt inbetween, thereafter the melt powder is applied onto the surface to be coated by using pressurized air.
The disadvantage of said method and apparatus, respectively, lies in that acetylene is most expensive, energy exploitation is uneconomical, in addition, quality of coating obtained by the method and apparatus does not meet requirements.
A process and an apparatus are also known which use PB-gas or natural gas as combustible gas. The disadvantage of this solution lies in that in order to prevent lateral deflection of the powder jet discharged in a slab-shape from the spraying head and thus to eliminate powder losses, slab-shaped cold air-jets are directed onto the powder jet. In order to prevent powder losses to the desired extent, a considerable quantity of cold air is required decreasing considerably the temperature of the flame needed for melting the powder, resulting in a lower efficiency of powder melting. As a consequence of the significant quantity of cold air energy required for melting increases considerably, stability of the melting flame decreases. Flame stability is further deteriorated by the fact that structural design of the spray head of known apparatuses does not exclude arrival of the air streams coming from different lateral directions and of uncontrollable intensity at the melting flame. |
/* ==========================================================================
Grey Theme
========================================================================== */
.t-purple {
.c-navigation,
.c-header {
background: $c__deep-purple;
}
.c-article__main a:not(.c-btn) {
color: $c__deep-purple;
}
.c-footer a {
color: $c__deep-purple;
}
}
|
// vim: ts=4:sw=4:nu:fdc=4:nospell
/**
* Ext.ux.FileTreeMenu
*
* @author Ing. Jozef Sakáloš
* @version $Id: Ext.ux.FileTreeMenu.js 112 2008-03-28 21:11:17Z jozo $
* @date 13. March 2008
*
* @license Ext.ux.FileField is licensed under the terms of
* the Open Source LGPL 3.0 license. Commercial use is permitted to the extent
* that the code/component(s) do NOT become part of another Open Source or Commercially
* licensed development library or toolkit without explicit permission.
*
* License details: http://www.gnu.org/licenses/lgpl.html
*/
/*global Ext */
/**
* @class Ext.ux.FileTreeMenu
* @extends Ext.menu.Menu
* @constructor
* Creates new FileTreeMenu object
* @param {Object} config A configuration object
*/
Ext.ux.FileTreeMenu = function(config) {
config = config || {};
var uploadPanelConfig = {
contextmenu:this
,buttonsAt:config.buttonsAt || 'tbar'
,singleUpload:config.singleUpload || false
,maxFileSize:config.maxFileSize
,enableProgress:config.enableProgress
};
if(config.baseParams) {
config.baseParams.cmd = config.baseParams.cmd || 'upload';
config.baseParams.dir = config.baseParams.dir || '.';
uploadPanelConfig.baseParams = config.baseParams;
}
// {{{
Ext.apply(config, {
items:[{
text:' '
,cmd:'nodename'
,iconCls:"icon_pencilGo"
},{
text:this.openText + ' (Enter)'
,iconCls:this.openIconCls
,cmd:'open'
,menu:{
items:[{
text:this.openSelfText
,iconCls:this.openSelfIconCls
,cmd:'open-self'
},{
text:this.openPopupText
,iconCls:this.openPopupIconCls
,cmd:'open-popup'
},{
text:this.openBlankText
,iconCls:this.openBlankIconCls
,cmd:'open-blank'
},{
text:this.openDwnldText
,iconCls:this.openDwnldIconCls
,cmd:'open-dwnld'
}]
}
}
,new Ext.menu.Separator({cmd:'sep-open'})
,{
text:this.reloadText
,iconCls:this.reloadIconCls
,cmd:'reload'
},{
text:this.expandText
,iconCls:this.expandIconCls
,cmd:'expand'
},{
text:this.collapseText
,iconCls:this.collapseIconCls
,cmd:'collapse'
}
,new Ext.menu.Separator({cmd:'sep-collapse'})
,{
text:this.renameText
,iconCls:this.renameIconCls
,cmd:'rename'
},{
text:this.deleteText
,iconCls:this.deleteIconCls
,cmd:'delete'
},{
text:this.newdirText
,iconCls:this.newdirIconCls
,cmd:'newdir'
}
,new Ext.menu.Separator({cmd:'sep-upload'})
,{
text: 'Add Tags on Upload',
menu: {
items: [new Ext.menu.Adapter(new Ext.form.TextField({
id: 'file_tree_panel_tags_textfield',
listeners: {
'change': function(me, newValue, oldValue){
Ext.get('file_tree_panel_tag_list_field').dom.value = newValue;
},
'focus': function(me){
me.el.up('li').removeClass('x-menu-list-item');
}
}
}), {
hideOnClick: false
})]
}
}
,new Ext.menu.CheckItem({
text: 'Unzip on Upload?',
hideOnClick: false,
checkHandler: function(me, checked){
if(checked){
Ext.get('file_tree_panel_unzip_checkbox').dom.value = 1;
}
else{
Ext.get('file_tree_panel_unzip_checkbox').dom.value = 0;
}
}
})
,new Ext.menu.Adapter(new Ext.ux.UploadPanel(uploadPanelConfig), {
hideOnClick:false
,cmd:'upload-panel'
,cls:'pointerOnHover'
})
]
}); // eo apply
// }}}
// call parent
Ext.ux.FileTreeMenu.superclass.constructor.call(this, config);
// relay event from submenu
this.relayEvents(this.getItemByCmd('open').menu, ['click', 'itemclick']);
}; // eo constructor
Ext.extend(Ext.ux.FileTreeMenu, Ext.menu.Menu, {
// configuration options overridable from outside
/**
* @cfg {String} collapseIconCls icon class for collapse all item
*/
collapseIconCls:'icon-collapse-all'
/**
* @cfg {String} collapseText text for collapse all item
*/
,collapseText: 'Collapse all'
/**
* @cfg {String} deleteIconCls icon class for delete item
*/
,deleteIconCls:'icon-cross'
/**
* @cfg {String} deleteKeyName text for delete item shortcut
*/
,deleteKeyName:'Delete Key'
/**
* @cfg {String} deleteText text for delete item
*/
,deleteText:'Delete'
/**
* @cfg {String} expandIconCls icon class for expand all item
*/
,expandIconCls:'icon-expand-all'
/**
* @cfg {String} expandText text for expand all item
*/
,expandText: 'Expand all'
/**
* @cfg {String} newdirIconCls icon class for new directory item
*/
,newdirIconCls:'icon-folder-add'
/**
* @cfg {String} newdirText text for new directory item
*/
,newdirText:'New folder'
/**
* @cfg {String} openBlankIconCls icon class for open in new window item
*/
,openBlankIconCls:'icon-open-blank'
/**
* @cfg {String} openBlankText text for open in new window item
*/
,openBlankText:'Open in new window'
/**
* @cfg {String} openDwnldIconCls icon class for download item
*/
,openDwnldIconCls:'icon-open-download'
/**
* @cfg {String} openDwnldText text for download item
*/
,openDwnldText:'Download'
/**
* @cfg {String} openIconCls icon class for open submenu
*/
,openIconCls:'icon-open'
/**
* @cfg {String} openPopupIconCls icon class for open in popup item
*/
,openPopupIconCls:'icon-open-popup'
/**
* @cfg {String} text for open in poput item
*/
,openPopupText:'Open in popup'
/**
* @cfg {String} openSelfIconCls icon class for open in this window item
*/
,openSelfIconCls:'icon-open-self'
/**
* @cfg {String} openSelfText text for open in this window item
*/
,openSelfText:'Open in this window'
/**
* @cfg {String} openText text for open submenu
*/
,openText:'Open'
/**
* @cfg {String} reloadIconCls icon class for reload item
*/
,reloadIconCls:'icon-refresh'
/**
* @cfg {String} reloadText text for reload item
*/
,reloadText:'R<span style="text-decoration:underline">e</span>load'
/**
* @cfg {String} icon class for rename item
*/
,renameIconCls:'icon-pencil'
/**
* @cfg {String} renameText text for rename item
*/
,renameText: 'Rename'
/**
* @cfg {String} uploadFileText text for upload file item
*/
,uploadFileText:'Upload Control'
/**
* @cfg {String} uploadIconCls icon class for upload file item
*/
,uploadIconCls:'icon-upload'
/**
* @cfg {String} uploadText text for word 'Upload'
*/
,uploadText:'Upload'
/**
* @cfg {Number} width Width of the menu.
* Cannot be empty as we have upload panel inside.
*/
,width:190
// {{{
/**
* Returns menu item identified by cmd. Unique cmd is used to identify menu items.
* I cannot use ids as they are applied to underlying DOM elements that would prevent
* to have more than one menu on the page.
* @param {String} cmd
* Valid cmds are:
* - nodename
* - open
* - open-self
* - open-popup
* - open-blank
* - open-dwnld
* - sep-open (for separator after open submenu)
* - reload
* - expand
* - collapse
* - sep-collapse (for separator after collapse item)
* - rename
* - delete
* - newdir
* - sep-upload (for separator before upload panel)
* - upload (for upload file item that does nothing)
* - upload-panel (for upload panel)
* @return {Ext.menu.Item} menu item
*/
,getItemByCmd:function(cmd) {
var open;
var item = this.items.find(function(i) {
return cmd === i.cmd;
});
if(!item) {
open = this.items.find(function(i) {
return 'open' === i.cmd;
});
if(!open) {
return null;
}
item = open.menu.items.find(function(i) {
return cmd === i.cmd;
});
}
return item;
} // eo function getItemByCmd
// }}}
// {{{
/**
* Sets/Unsets item identified by cmd to disabled/enabled state
* @param {String} cmd Item indentifier, see getItemByCmd for explanation
* @param {Boolean} disabled true to disable the item
*/
,setItemDisabled:function(cmd, disabled) {
var item = this.getItemByCmd(cmd);
if(item) {
item.setDisabled(disabled);
}
} // eo function setItemDisabled
// }}}
// {{{
/**
* destroys uploadPanel if we have one
* @private
*/
,beforeDestroy:function() {
var uploadPanel = this.getItemByCmd('upload-panel');
if(uploadPanel && uploadPanel.component) {
uploadPanel.component.purgeListeners();
uploadPanel.component.destroy();
uploadPanel.component = null;
}
} // eo function beforeDestroy
// }}}
}); // eo extend
// register xtype
Ext.reg('filetreemenu', Ext.ux.FileTreeMenu);
// eof
|
EGFR inhibitors as the first-line systemic treatment for advanced non-small-cell lung cancer.
Drugs that target the EGFR have a major impact on the treatment of advanced non-small-cell lung cancer (NSCLC). EGFR mutations in NSCLC are associated with a dramatic and sustained response to EGFR tyrosine kinase inhibitors (TKIs). This review summarizes the results of randomized trials using EGFR TKIs or EGFR monoclonal antibodies with chemotherapy in the first-line setting, and discusses several unresolved issues regarding the use of the EGFR TKIs as the first-line therapy in advanced NSCLC. |
Panasonic to move Europe headquarters from UK to Amsterdam - DyslexicAtheist
https://www.bbc.com/news/business-45351288
======
bdz
[https://www.businessleader.co.uk/from-london-to-amsterdam-
pa...](https://www.businessleader.co.uk/from-london-to-amsterdam-panasonic-
set-to-move-its-european-headquarters/51049/)
>Up to 20 people could be affected out of a staff of 30
So it's just a ghost office for tax purposes.
------
digitalengineer
“In the case of Panasonic, it’s concerned that if the U.K. gets designated a
tax-haven by Japan it could be saddled with back taxes back home. So moving to
stay regionally headquartered within the European Union removes that risk.” .
Eh? Obama called he Netherlands a tax haven as well. Wikipedia: “The
Netherlands has been known internationally, since at least the 1970s, as a tax
haven”. Source:
[https://en.m.wikipedia.org/wiki/Corporate_tax_in_the_Netherl...](https://en.m.wikipedia.org/wiki/Corporate_tax_in_the_Netherlands)
~~~
qbrass
The Netherlands may be considered a tax haven colloquially, but they're not
blacklisted as one.
------
coldtea
Which is neither here, not there.
Companies are opportunistic and will go wherever makes them more money, has
less tax, and laxer laws. That why tons of factories, support, and even
development jobs moved out of Europe and US and into third world countries
with el cheapo wages and laws accommodating sweatshop practices.
In this case, it's because of easier import/export procedures and bureaucracy
for selling to the rest of the EU.
When the UK is able to set its own lower tax rates and cuts special deals for
such matters (which they'll do), lots of companies will flock back there too
(same as they did with Ireland).
~~~
matthewmacleod
Companies are unlikely to flock back to the UK is it has expensive trade
barriers with the rest of the European market, regardless of the “tax deals”
which are cut.
~~~
kyriakos
Precisely, companies want free access to eu market, not just geographical
presence in Europe, therefore UK will only make sense for UK market once
brexit is complete.
------
Brakenshire
Techcrunch reported on most of the article from Nikkei, except this part:
> Of the 20 to 30 people employed at the London office, the 10 to 20 who
> handle auditing and financial operations will be moved to the Netherlands,
> with only investor relations staff staying.
Is the headquarters nominal, or does it pay signicifant tax where it is
located?
------
kuro68k
Not the first, and won't be the last. We have to stop this madness.
~~~
fasafsaf3
We can either stop this madness or accept the results of a democratic
referendum.
~~~
la_oveja
A democratic referendum can be rigged by the emotions ruling at the moment of
said referendum. You'd think if it would be repeated it would get the same
outcome?
~~~
coldtea
So let's have people who know our best interests and are not "rigged"
themselves decide for us?
~~~
la_oveja
Well, in my opinion the "people who know our best interests" are the ones who
sold Brexit as the new solution for everything, skipping the true nature of
it.
------
interdrift
Brexit, the present that keeps on taking
~~~
raverbashing
But they will be able to buy their straight bananas or have their blue
passport back or some other BS I forgot
|
PUSHKIN HOUSE MUSIC SALON: Antonina Suhanova Piano Recital
In her Pushkin House recital programme Latvian pianist Antonina Suhanova explores creative and personal bonds between early 20th century Eastern European composers. Brought together by their love of music and mutual teachers, Kalnins, Vitols, Arensky, Prokofiev, Rachmaninov and Siloti socialised, conversed and inspired each other’s masterpieces, engaging in fierce disputes. Based either in Moscow or Saint Petersburg, some chose to stay in Russia, others acted as heralds of Russian music abroad. Some chose to uphold revered traditions, others created bold new styles. The programme invites the audience to reflect on the diversity of the styles of these five composers united by their love and appreciation of the Russian musical tradition.
Programme:
KalninsAt Friend’s Grave - In Memoriam Emils Darzins (1913)
Vitols Ten folk songs Op. 29
Arensky Piano pieces Op. 53
Prokofiev Sonata no. 4, Op. 29, ‘From Old Notebooks’
Rachmaninov Sonata no. 1, Op. 28
Rachmaninov/Siloti Vocalise
Latvian pianist Antonina Suhanova has been performing on international stages since 2000. At the age of 5 she began piano studies at Pavuls Jurjans Riga Music School with Ludmila Kiselenko, making her concerto debut at the age of 8, continuing her professional development at Jazeps Medins Riga Secondary Music School with Gunta Boža and at Jazeps Vitols Latvian Academy of Music with Professor Juris Kalnciems. In 2012 Antonina commenced her studies at the Guildhall School of Music and Drama (GSMD, London) under the tutelage of the distinguished British pianist Ronan O’Hora. She has participated in numerous masterclasses of world-renowned pianists, including Vladimir Ashkenazy, Dmitri Bashkirov, Boris Berman, Idil Biret, Pavel Gililov, Jaques Rouvier, Matti Raekallio, Richard Goode, Robert Levin and Yefim Bronfman. Antonina holds Bachelor of Music, Master of Performance and Artist Diploma degrees from GSMD, and her studies have been generously supported with a full scholarship throughout the years.
Antonina Suhanova has given performances at the Great Guild Hall in Riga, Moscow International House of Music, Erin Arts Centre in Isle of Man, Jerwood Hall, LSO St Luke’s, St Martin in the Fields, St James’s Piccadilly, Milton Court Concert Hall and Barbican Hall in London. She has appeared as a soloist with the Tallinn Chamber Orchestra, London’s Silk Street Sinfonia, “Sinfonia Concertante” Chamber Orchestra, Latvian National Symphony Orchestra, Liepaja Symphony Orchestra, “Moscow Virtuosi” Chamber Orchestra, and other collectives, collaborating with such distinguished conductors as Andris Nelsons and Vladimir Spivakov, amongst others. Antonina has performed at renowned festivals in the United Kingdom, Italy, Germany, Netherlands, Latvia, Switzerland, Austria and Russia. She made her debut performance at the Barbican Hall with the Guildhall Symphony Orchestra under the baton of Adrian Leaper as a finalist of the Guildhall Gold Medal Prize in May 2016, returning in December of the same year to perform a solo recital. In 2017 she was invited to participate in the Academie de Musique Lausanne in Switzerland where she became the festival laureate together with her duo partner Alexandra Lomeiko (violin).
Performances of Antonina Suhanova have been broadcasted by Latvian Radio 3 “Klasika”, Russian TV Channel One, Switzerland radio Espace 2 and BBC 3. Antonina is the winner of Hattori Foundation Senior Award, Kenneth Loveland Gift, Help Musicians UK, Drake Calleja Trust, and the William Brown prize in the Scottish International Piano Competition (2017). In March 2018 she was nominated for the International German Piano Award 2018.
Antonina Suhanova completed the Artist Diploma course at GSMD in July 2018, and was awarded a fellowship for the 2018 / 2019 academic year. In November 2018 she made her debut performance at the Wigmore Hall, being broadcast live on the BBC Radio 3. |
Dressed in camouflage, often with an AK 47 slung over her shoulder, Vancouverite Hanna Bohman's life on the front lines in Syria is showcased in the documentary, "Fear Us Women."
The documentary about the YPJ — the female brigade of the Kurdish People's Protection Units — is told through Bohman's own experiences with the group; many of her personal videos made the final cut.
The 48-year-old first made contact with YPJ recruiters online and says she spent time in Iraq and Syria over the last three years volunteering with the female fighters battling ISIS, some of which included combat on the front lines.
"I didn't go there to kill people. I went there to help people but I realized in doing what I was doing, there would be times where I'd have to kill an enemy," said Bohman.
She had no prior military experience, and only four hours of weapons training the first time she arrived in Syria, after she says she was smuggled into the country.
Bohman admits she's been called crazy, but says she first decided to go because she was looking for something "important" to do with her life.
Female Fighters
The nearly 30-minute long documentary by RYOT is directed by Academy Award nominated director David Darg and executive produced by actress Olivia Wilde.
Producer Diego Traverso was first introduced to the female fighters in Syria while working for a humanitarian group.
"Some of the units that were protecting me as a journalist and humanitarian were women, so I was very intrigued," said Traverso.
That curiosity led to creation of the short documentary, but despite dozens of interviews with Kurdish women, Traverso says both he and Darg wanted someone to bridge the gap between the female fighters' stories and a Western audience.
"We ended up seeing on Facebook a clip from Hanna and I was like 'oh this is perfect'," said Traverso.
Bohman has been back in Canada since the summer, but is still very focused on bringing awareness to the YPJ while promoting the documentary, which was screened at the Whistler Film Festival.
"My hope is that women will look at this and realize that men aren't going to come and rescue us. We have to take care of ourselves," said Bohman. "I want to make the YPJ a household word." |
Q:
Angular js - Error: [$parse:lval] Trying to assign a value to a non l-value
I have an error in this line of my code, but the code fulfills its mission.
I do not understand what can happen. I am very new with angular
<md-list-item ng-show="cargando == false" ng-repeat="idea in ideas2 = (ideas | orderBy : '-Created' | filter: filterData | filter:buscaAprobadas)" ng-class="md-1-line && { evaluada: idea.Estado !='Aprobada'} " ng-click="idea.Estado != 'Aprobada' || idea.selected = !idea.selected">
A:
Your last comparison: idea.selected = !idea.selected is an assignment. You want to change it to idea.selected == !idea.selected or something similar.
|
Many aspects of Americans' lives work together to influence their opinions on issues such as global warming, animal testing, and sending people to space.
(Photo: Kevin Case/Flickr)
Tell me your age, race, gender, and political leanings, and I'll tell you your likely views on issues such as human-caused global warming, GMO foods, and childhood vaccines. I'm no psychic, but I can play the odds: Americans' opinions about these matters of science and technology align strongly with certain personal characteristics, according to a new survey.
The survey, which comes from analysts at the Pew Research Center, offers a fascinating glimpse into the many aspects of Americans' lives that converge to influence how they think, and perhaps vote, about science issues. The findings belie the common assumption that science is apolitical or acultural; whether or not they should, people's cultural environments play a big role in how they think about science. The Pew study can also act as a tip sheet for those wishing to change others' minds about hot-button topics such as GMO foods and vaccines, because it identifies the topics for which a knowledge of facts really helps—and for what topics it doesn't.
The survey required a representative sample of 2,002 American adults on their landline and cell phones. The scientists performed statistical analyses to tease out which characteristics affected people's views on different issues strongly, independent of other factors.
Here's a short list of some important science questions and the personal characteristics that held the greatest influence over people's opinions on them:
Is global warming real and human-caused? Political party, age.
Should we frack more? Political party, age.
Did humans arise through evolution? Age, religion or church attendance.
Are childhood vaccines safe? Race. Black Americans are more likely than whites to say vaccines are generally safe for kids.
Should sick people have access to experimental drugs before they're fully tested? Age, race. Black Americans are much more likely than Americans of other races to think experimental drugs should not be made available early.
Are genetically modified foods safe to eat? Education or science knowledge.
Is it okay to use animals in research? Age, education or science knowledge, gender.
Is it important for NASA to send humans into space? Gender. Men are more likely to say "yes" to this question, which presents a great argument that astronomers need to work on how welcoming their field seems to women. Win the hearts of women and you'll win a large contingency of voters who affect NASA funding.
It's not encouraging to see that people's opinions on topics such as global warming and vaccines hew with factors like political party and age. The former presents the risk that people may automatically decide on science based on their favorite party, instead of thinking through the issue by themselves. The latter is impossible to change.
In addition, education and knowledge have only a weak effect—if one at all—on people's opinions about whether vaccines are safe for healthy children, or whether America should frack more or drill more for oil offshore. These are arguments proponents must win in other ways.
Still, there's some hope. Having better education and science knowledge appears to strongly alter people's opinions on animal testing, nuclear power plants, and GMO foods. More education and knowledge also affect people's opinions on the need for limits on power plants' emissions, the reality of human-caused climate change, and evolution. That's great because education and knowledge are straightforward—if not always easily obtained—objectives.
As for the rest, scientists, politicians, and activists will just have to get creative. |
Radiologic appearance of a bronchial granular cell tumor with secondary obstructive changes.
Bronchial granular cell tumor is a rare neoplasm. This report describes a 16-year-old female with this tumor in the right upper lobe. An ill-defined mass with peripheral infiltration was recognized on a chest radiograph. Thoracic computed tomography showed an intrabronchial mass lesion at the proximal portion of the bronchial bifurcation of the right B1 segment. The tumor completely occluded the bronchial lumen and thus caused obstructive changes of the lung distal to the tumor. |
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OHL
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Photo: Erie Otters forward and 2015 prospect Connor McDavid (L) is returning from an injury just in time to compete for Team Canada at the 2015 World Junior Championship (courtesy of Minas Panagiotakis/Getty Images)
When Team Canada embarks on its mission to capture a gold medal at the 2015 World Junior Championship, they will do so with a group steeped in offensive skill, both up front and on the back end. Read more»
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Photo: Niagara IceDogs forward and New York Islanders prospect Josh Ho-Sang is one of the more outspoken, young players among NHL prospects (courtesy of Vaughn Ridley/Getty Images)
As exciting as hockey players are on the ice, they are notorious for being boring off the ice. If you’ve heard one post-game interview, you’ve heard them all. Most hockey players respond to questions with the same robotic cliches – “We, uhh, just need to, uhh,focus on the, uhhh, next game. We need to just, uhhh, continue to play our, uh, style of game; play a full, uh, 60 minutes, get, uh, pucks in deep and finish our checks, get shots on, uh, net, and create, uh, chances…uh.” Read more»
Erie Otters forward Connor McDavid will have a sizable stage on which to display his talents when the 2015 World Junior Championship begins on December 26th. But McDavid and 39 other prospects for the 2015 NHL Draft will have their own showcase less than a month later when the 2015 BMO CHL/NHL Top Prospects Game takes place in St. Catharines, ON. Read more»
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The Philadelphia Flyers were given what they hope is a glimpse of their future after a two-point performance by rookie forward Scott Laughton that included his first NHL goal. The goal was one of a quintet scored by the Flyers in a 5-1 win over the Eastern Conference’s bottom team, the Carolina Hurricanes. Read more» |
The invention relates to the decoding of encoded data.
When data is moved from place to place, it is often the case that the transfer process will create errors in the data. Accordingly, it is common practice to encode data to mitigate the impact of errors introduced by a transfer process. Normally, encoded data has to be decoded in order to be put to its intended use. Both the encoding and decoding of data represent a processing burden. This burden can be quite heavy in the case of modern encoding schemes. The use of encoding schemes to protect against data transfer errors is widespread but such use is particularly heavy in the telecommunications industry, especially in the wireless communications sector.
There exists a wide range of data encoding techniques and complimentary data decoding techniques. In the wireless communications sector, convolutional encoding techniques are commonly used. Various techniques can be used for decoding a convolutionally encoded signal, such as the Viterbi algorithm, the MAP (maximum a posteriori probability) algorithm and the log-MAP algorithm. Convolutional encoding and Viterbi, MAP, log-MAP and max-log-MAP decoding algorithms will be well known to those skilled in the art of wireless telecommunications engineering but readers less familiar with the field can find an introduction to these subjects in the book entitled “Digital Communications”, by John G. Proakis, fourth edition, published by McGraw-Hill.
A paper by Gambe et at entitled “An Improved Sliding Window Algorithm for Max-Log-MAP Turbo Decoder and Its Programmable LSI Implementation” (IEICE Trans. Electron., Vol. E88-C, 3 Mar. 2005, pages 403 to 412) describes a sliding window approach to max-log-MAP turbo decoding in which certain metrics calculated in one turbo decoding iteration are carried over to provide window commencement metrics for a subsequent iteration. |
not even near enough.
the joys of living in urban environment, ya gotta fight traffic to get there, hope there isnt a wait to use the range, hope the range officers arent up your ass, hope the range is operating properly, etc.,etc.,etc.
sorry, but shooting should be done in a relaxed atmosphere. I have actually left the range early due to the idiots around me. oh well.
"Your either part of the problem or part of the solution, which are you?"
Once in a blue moon.
Why go to a public range if you live in the coutry?? [:)]
Plenty of space, no one to deal with, and very relaxing. Plus, everynow and then, you get to shoot at some rabbits/squirrels.
But I must admit, to sight my guns in, I had to go to a local indoor range to shoot at certain distances. (50 yards)
"The price good men pay for indifference to public affairs is to be ruled by evil men." - Plato
Once every 2-3 weeks for the indoor range, but my aunt & uncle own several hundred acres of woodland in Iowa. I go there 2-3 times a week. I am very lucky, the indoor range is ok for ARs but you cant kill a watermelon, pumpkin, or Lawn Boy (THAT was fun) at an indoor range! Too bad Iowa is not ClassIII friendly, I would be bankrupt in a week... John
Damn, I use to go twice a week, then I will blame the weather for not being able to go, now is only when my buddies go.
I need to take this seriously again, and try to go at least once a week.
Thanks for the reminder.
Under normal circumstances Monday through Friday. Mix that up with both day and late night shooting, more recently day and night shooting the same "day". I don't usually mess with it on weekends if I can keep from it. Of course the heavier winter months of Jan. and Feb. slow things down quite a bit.
As a side note, none of this is in relation to a public range. I've got private areas to work with.
I am fortunate enough to live 10 miles from the largest civilian shooting facility in the U.S., Ben Avery Shooting facility in Phoenix Arizona. I go to their main range 2-4 times a month and then take classes on various other ranges in the facility 2-3 times a month. The main range chardes $5 a day. The only downside is that, as with all good things, the range is coming under pressure from real estate developers who are in bed with local politicans are creating housing developments next to the range and complaining about you guessed it noise. Kind of like the idiots that buy houses next to airports and then lobby to get them shut down. One day I fear that the range will be gone. My rant is done.
Unfortunately, the only time I get out with my AR is for FDCC shoots. I've been so damned busy lately with class that my weekends get devoted to reading hundreds of pages or doing research. I'd like to go more, but the nearest range (other than one I don't want to use on account of bad relations with FDCC) is in Lake City, and the other is equidistant in the other direction. It drives me insane [banghead]
once a week becuase tahts all I can afford..
my tuesdays go like this..
*wake up.. take a dump..
*take kids to school < my day off so wife gets to sleep in :) >
*from droping off kids go to buy ammo.. $$$$ < a gotta skip a week sometimes due to this >
*stop by friends houses to see if they have any broken TV' or whatever that needs to die.
*arrive at the place I shoot
*after a couple of hours .. go pick up kids from school < its semms like the day goes by in 15 minutes when at the range>
*go home
ps... not realy a range its a land lease type deal .. no range nazis.. do just about anything you want aslong as you clean up aftre your self.
Originally Posted By Sl_AYER:
I am fortunate enough to live 10 miles from the largest civilian shooting facility in the U.S., Ben Avery Shooting facility in Phoenix Arizona. I go to their main range 2-4 times a month and then take classes on various other ranges in the facility 2-3 times a month. The main range chardes $5 a day. The only downside is that, as with all good things, the range is coming under pressure from real estate developers who are in bed with local politicans are creating housing developments next to the range and complaining about you guessed it noise. Kind of like the idiots that buy houses next to airports and then lobby to get them shut down. One day I fear that the range will be gone. My rant is done.
View Quote
I go there a couple time a month and yes, they are trying to develop the land around there. Ben Avery has to be one of the premier if not the best public ranges in the USA - let's keep it that way.
I find myself going to the range more and more often. I used to go once a month. Now I go every weekend. I am getting to know the people who work there and the other guys that go out there regularly. It is the only place I can go and be somewhat alone- away from my wife and daughter. When I'm not at the range, I am thinking about it. Is that sad or what?
Originally Posted By excitableboy:
I find myself going to the range more and more often. I used to go once a month. Now I go every weekend. I am getting to know the people who work there and the other guys that go out there regularly. It is the only place I can go and be somewhat alone- away from my wife and daughter. When I'm not at the range, I am thinking about it. Is that sad or what?
View Quote
I do the same. It's time to clear the mind, like wiping away the little things. I think it is good therapy.
I try to go once a week, usually doesn't work out that way. I live in the SanFrancisco East Bay, so city ranges for me. Family, home, and unfortunately work, are the biggest obsticals. I would prefer daily but would settle for weekly, currently about once every three weeks.
i go EVERY other saturday like clockwork. my wife dosent even try and talk me out of it anymore. i can also squeeze in a mid-week trip 2 or 3 times a month
so i guess i go 4-6 times a month, not enough but it keeps me from spending too much on ammo.
the only thing is i always act like each trip to the range will be my last so i find myself dragging every gun i own out every time.
I normily go once a week.I work night's so i get to go during the week when it's nice and empty.Forget the week end's.The range master is a cool guy,long as you don't do some thing stupid,other wise he let's me put out clay's and full soda can's.This help's keep it fun.With the weather down here now i get my ass out of the bed and go,tired or not,the morning's are just to beautiful to waste.
Originally Posted By Sl_AYER:
I am fortunate enough to live 10 miles from the largest civilian shooting facility in the U.S., Ben Avery Shooting facility in Phoenix Arizona. , as with all good things, the range is coming under pressure from real estate developers who are in bed with local politicans are creating housing developments next to the range and complaining about you guessed it noise. Kind of like the idiots that buy houses next to airports and then lobby to get them shut down. One day I fear that the range will be gone. My rant is done.
View Quote
Yep, same-same on the East side of Phoenix with Rio Salado. Great facility. It has been there for years. Now, there are both new neighbors and new rules/hours. It is probably on the same track as Ben Avery. I think it is epidemic with ranges across the country. No matter how far away you build it, they (neighbors) will come.
i normally go wed. nights, saturdays, and sundays. unfortunately the weather here has been so crappy this year that i've been forced to go wed. nights, staurdays, and sundays in the rain. My pistol permit should be in shortly also... i'm pretty sure that will not serve to mitigate my ammo expenditures.
I just joined my first gun range so I'm hoping to go at least 2-3 times a week. But since it's getting dark earlier now, I'll have to stick to the weekends for my AR. Indoor ranges there are for pistols only(or .22 rifles), so any after dark shooting will just be my Walther P22. My AR shooting will end up depending on my ammo expenditures as well. I'm sure I could easily go through a few hundred rounds in an afternoon of shooting with the AR, so I may have to limit myself to 200 rounds in a weekend to keep my expenses in check. J
No ranges here in the Florida Keys, im right down in Key West, so we improvise, we go out on my fishing boat about 8-10 miles and shoot at floating targets and throw skeet to shoot at with our 12 gauges.The flying fish make good targets to.I have family in the mainland of Florida that have land in the middle of the country.
Shoot two or three times a month on water and once every two months on the farm in the mainland.
I would like to shoot every weekend on land really, the movement of the sea is sometimes a bit too much.
I used to go every Thirsday when I had an easy semester. Now I only get out once every couple months. I was actually going to go today, but it was raining, and I did not feel like getting soaked in between classes. |
It's hard to get a sense of what a food shortage is like unless you've lived through one, but this tidbit from Venezuela serves as a chilling illustration.
The lines to get into government supermarkets are so long that people mark their arms with their place in line. It's not a permanent tattoo — just a pen — but the point is to make sure that the long lines stay as orderly as possible.
It looks like this:
The Road to Serfdom game in Venezuela just got real -- human tattooing for food privileges pic.twitter.com/ceKJycftOK — TakingHayekSeriously (@FriedrichHayek) March 9, 2014
According to a source familiar with what's going on, this number-scribbling takes place outside large cities like Caracas, and it doesn't happen in private supermarkets. However, private supermarkets can set a limit to the number of items a person can buy. For example: You can only pick up 4 liters of milk, 2 liters of oil, 2 kilos of sugar etc.
And that's if the market even has those items.
People also have numbers on their ID cards, which decide which days they can even get in line to shop at supermarkets like San Cristobal's Bicentenario, according to AFP.
Protests taking place all over the country aren't helping either. Demonstrators have been building barricades, which are slowing the flow of goods from place to place.
From AFP:
Armando Mirando, vice president of the Tachira State Bakeries Association, told AFP that San Cristobal could run out of bread by Tuesday...
"We already had shortages before and now nothing is arriving," Mirando said after addressing a "peace conference" organized by the government to end the protests but shunned by the opposition as a sham.
Most shops and restaurants are closed in the city of 260,000 people.
On Friday, Maduro got on TV and said that smuggling food into the country is more profitable than selling cocaine.
If you had to stand in this line (in San Crisobal) you would understand why. |
package com.yaoyumeng.v2ex2.model;
import org.json.JSONException;
import org.json.JSONObject;
import java.io.Serializable;
/**
* Created by yw on 2015/5/2.
*/
public abstract class V2EXModel implements Serializable {
private static final long serialVersionUID = 2015050101L;
abstract public void parse(JSONObject jsonObject) throws JSONException;
}
|
Of Money, Responsibility, and Pride - silenteh
http://veridicalsystems.com/blog/of-money-responsibility-and-pride/
======
AaronFriel
This is a mistake. The Apache foundation doesn't sell $250/hour consulting
gigs for its primary source of revenue. Neither does the Linux Foundation, the
SQLite Consortium, or other massive, mission-critical open source products.
This is the wrong funding model. It keeps money in OpenSSL developer's
pockets, but there is no financial incentive for any OpenSSL developer to work
on foundational improvements to OpenSSL. He said himself: there is over
$100,000 in open contracts for competent developers to work on non-
foundational improvements to the project. If you are an enterprising developer
with good C skills and a knack for crypto projects and you apply to work for
the OpenSSL foundation, are you going to start servicing that $100,000 pool of
contracts or are you going to pretend that money doesn't exist and live on
ramen?
If nearly all of OpenSSL's revenue comes from clients that want OpenSSL to
meet their particular needs, then none of that money is going to developers to
strengthen OpenSSL's foundation. This is why OpenSSL looks like a hodgepodge
of hacks upon hacks in order to accomplish narrow goals with limited impact
testing. It should be no surprise to anyone else: clients are literally paying
OpenSSL developers for this, and nothing else.
Who is paying OpenSSL for developers to clean up the code base and remove
ancient #IFDEFs? Who is paying OpenSSL for developers to analyze code paths
and do case analysis? Who is paying OpenSSL for developers to write unit tests
or even have a test harness at all?
No one will pay an hourly rate to accomplish these tasks. Google is not going
to pay by the hour for a developer to stare at a function until they grok it;
they want a feature. Joe Company will not pay for developers to write unit
tests, they want OpenSSL to handle $QUIRK from a vendor's system, or to know
how to make their code handle it.
This model needs to go away. Competent OpenSSL developers time is too valuable
to waste on client asks. Their project is too important, and as long as the
money is flowing only for novel features and not structural improvement, then
that money will dictate that only new features are developed.
~~~
uuid_to_string
This is one of the better comments I have seen on OpenSSL in the past week.
Well said.
"This is why OpenSSL looks like a hodgepodge of hacks upon hacks in order to
accomplish narrow goals with limited impact testing."
It doesn't just look like a hodgepodege of accumulated hacks, it is a
hodgepodge of accumulated hacks. :)
"It should be no surprise to anyone else: clients are literally paying OpenSSL
developers for this, and nothing else."
One could say this with respect to many popular open source projects,
including ones with corporate sponsorship. The complexity just keeps building
over time and there is no such thing as "finished, accepting bug fixes only".
"Who is paying OpenSSL for developers to clean up the code base and remove
ancient #IFDEFs? Who is paying OpenSSL for developers to analyze code paths
and do case analysis? Who is paying OpenSSL for developers to write unit tests
or even have a test harness at all?"
Those are rhetorical questions. We know the answers. Alas, when the people who
pay for (open source) software and consulting pay to have "features" removed
instead of added, "pigs will fly".
Doug McIllroy is quoted as saying, "The hero is the negative coder".
(Just in case this need explanation: Prof. McIllroy is the mind behind UNIX
pipes and one of computer science's most prominant contributors. "Negative
coder" means someone who removes code instead of constantly adding, or
"committing", new code.)
We could really use some more heros. And as we switch away from OpenSSL there
will be a lot of links to libssl to remove.
Meanwhile some people have been writing and testing small, auditable and
usable open source crypto, more or less for "free".
[http://tweetnacl.cr.yp.to](http://tweetnacl.cr.yp.to)
My guess (and hope) is that pathological requests for "features" to be added
would be met with heavy scrutiny. The authors already have day jobs in
academia.
~~~
dfc
> Meanwhile some people have been writing and testing small, auditable and
> usable open source crypto, more or less for "free".
With all due respect that is complete bullshit. I do not care that you put
quotes around free. Writing "free" will never be considered to include sums in
the hundreds of thousands of dollars. More importantly blatant lies like this
muddy the debate and set outrageous expectations. The Nacl project gives the
following description of funding:
NaCl was initiated by the CACE (Computer Aided Cryptography Engineering)
project funded by the European Commission\'s Seventh Framework Programme
(FP7), contract number ICT- 2008-216499. CACE activities were organized
into several Work Packages (WPs). NaCl was the main task of CACE WP2,
\"Accelerating Secure Networking,\" led by Tanja Lange (at Technische
Universiteit Eindhoven) and Daniel J. Bernstein (at the University of
Illinois at Chicago, currently visiting Eindhoven). CACE nished at the
end of 2010 but NaCl is a continuing project.
...Many of the algorithms used in NaCl were developed as part of
Daniel J. Bernstein\'s High-Speed Cryptography project funded by
the U.S. National Science Foundation, grant number ITR-0716498.
I found the funding information for ITR-0716498. djb is listed as the PI for
the project.[^1] I could only find the high level funding of
ICT-2008-216499.[^2] (wtf EU?) CACE WP2 is only one component of the project.
I would love it if someone with better knowledge of EU funding can find the
funding for the WP2 line item. The figures are:
NSF ITR-0716498 funding: (USD) 400,000.00
EU 2008-216499 funding: (EUR) 4,733,078.00 ***NEED WP2 line item***
The tweetnacl implementation lists two more funding sources. As above it was
easy to locate the NSF funding but I totally struck out for the nwo funding:
NSF 1018836 funding: (USD) $436,203.00[^3]
NWO grant 639.073.005 funding: ???????????
Don't get me wrong, I have a lot of respect for djb and I think he and his
coworkers deserve every fractional euro/dollar of funding that they received
but they did not work for free. Most importantly they should not be expected
to work for free.
[^1]:
[http://www.nsf.gov/awardsearch/showAward?AWD_ID=0716498](http://www.nsf.gov/awardsearch/showAward?AWD_ID=0716498)
[^2]:
[http://cordis.europa.eu/projects/rcn/85344_en.html](http://cordis.europa.eu/projects/rcn/85344_en.html)
[^3]:
[http://www.nsf.gov/awardsearch/showAward?AWD_ID=1018836](http://www.nsf.gov/awardsearch/showAward?AWD_ID=1018836)
NB: This is the nwo funding site:
[http://www.nwo.nl/en/funding](http://www.nwo.nl/en/funding) I think the
english version may have a reduced set of features. I can not find the this
grant information on the site.
~~~
uuid_to_string
Wow. I guess "more or less" was not strong enough wording for you?
The point is that using something like NaCl costs you, the developer/user,
nothing more than if you are using OpenSSL.
Do you agree?
~~~
dfc
No, "more or less for free" is not close to hundreds of thousands of dollars
plus whatever funds came from the EU and NWO.
I have to say I am confused about your reply in the first sentence you seem to
acknowledge that the wordingwas related to the cost of "writing and testing"
crypto software. However in the second sentence you seem to indicate that your
thesis was about the switching costs users face. Which is it? You did not say
I get to use nacl "more or less for free" you said that "people have been
writing and testing small, auditable and usable open source crypto, more or
less for 'free'." That quote seems to be about the cost of creation not the
switching costs.
Do you think djb et al produced nacl "more or less for free?"
~~~
uuid_to_string
I think you misunderstood what I meant.
I mentioned "free" only to point out that there is no financial cost to
switching to it. I guess I did not type the sentence with enough care; words
are missing. My apologies.
I imagine people would be willing (and are accustomed) to paying for software
of similar quality.
But I'm also wondering why this bothered you so much.
Does it make a difference that grants were received?
Is the funding not transparent enough?
The blog article on OpenSSL mentions payments for consulting and "features" to
be added to OpenSSL.
Should I be concerned about what those features are, and who is paying for
them? Are you concerned?
I'm just nterested in cleaner code than OpenSSL's. NaCl looks cleaner to me.
Maybe I'm wrong. But I'd rather be compiling programs that use libnacl or some
other simpler alternative than ones that use libssl.
We all have to make decisions about what software we choose to use, even if we
are not cryptographers.
I see nothing wrong with discussing alternatives to OpenSSL. This bug has been
a real PITA.
~~~
dfc
> I mentioned "free" only to point out that there is no financial cost
> to switching to it. I guess I did not type the sentence with enough
> care; words are missing. My apologies.
It speaks highly of your character that you say this to the jerk on the
internet said you were full of shit.
> But I'm also wondering why this bothered you so much.
Because crypto is important. A lot of harmful attitudes/mindsets are
reinforced if people think NaCl was created in the authors spare time and did
not require funding:
\- "Why should I donate to GnuPG/OpenSSL/Tor/Mozilla(NSS)? Those NaCl devs
wrote NaCl for free."
\- "How hard could it be to implement a crypto library? Nacl was a side
project. The Nacl devs 'have day jobs in academia' and created nacl in their
spare time. They did it for free, so they obviously didn't need to spend money
on testing environment, research material or hire/consult experts. On the
other hand look at SelfiesMadeEa.sy they raised serious cash and had to quit
their jobs because they _tackle hard problems_."
\- "Obama and the rest of gubmint are taxing me to death. Government should be
pay for the military and maybe some roads; not waste money on liberal
academics in ivory towers, maplethorpe and those pinkos from NEA or some
stupid robot/telescope that cant do metric conversions."
\- "OMG NSA is evil. USA does nothing but invade countries and privacy."
> Does it make a difference that grants were received?
No it does not make a (negative/harmful) difference that grants were received.
I think it is a shining example of modern civil society; you have the US, NL
and the EU teaming up to fund strong crypto by top notch folks from a number
of countries. Governments should fund research, applied and basic, and they
should be encouraged to fund more of it.
Somewhat tangential: Knowledge of the grants also seeks to eliminate the
idiocy in the latter two examples above. People need to be reminded that big
government is not always an evil force, governments can be a force for good. I
do not know if you saw my other comment about tor funding but tor had revenue
of \$2+ million in 2012 and 60% came from US government. I don't know where
you are from but I bet you have met a simple minded moron wearing a tea party
costume or trendy European threads that will not stop complaining about the
evil Obama surveillance administration. Blow their minds and ask them to wrap
their heads around the:
\- $800k from DoD for "Basic and Applied Research and Development in Areas
Relating to the Navy Command, Control, Communications, Computers,
Intelligence, Surveillance, and Reconnaissance"
or
\- $350k from State for "Programs to Support Democracy, Human Rights and
Labor" and "New America Foundation: International Programs to Support
Democracy, Human Rights"
> Is the funding not transparent enough?
If this is in regards to the lack of numbers from NWO or the EU I am sure that
I am at fault. (I also think one of djb's EU grant numbers might have a digit
transposed) I imagine that the dutch version of nwo.nl is easier to use.
> The blog article on OpenSSL mentions payments for consulting and
> "features" to be added to OpenSSL.
> Should I be concerned about what those features are, and who is paying
> for them? Are you concerned?
I think we should be concerned that OSF is not doing a better job highlighting
sponsors and attracting new ones. It should be easier for someone with check
writing authority at big.corp.com to stumble across the sponsors information
and think to themselves "hey, we should drop some petty cash on these folks.
We use the product and I bet the marketing folks would appreciate the bump in
visibility for a fraction of the cost of our latest failed social network
branding efforts." If I was OSF I would look at the \$2 million tor brought in
and ask myself "maybe we could do a better job of sponsor outreach? Tor is
important to these people that wrote checks and tor uses libssl-dev, I wonder
if there is an opportunity?"
------
tptacek
Could someone involved with the OpenSSL Foundation and the OpenSSL project
maybe pitch in with a quick description of how the project is managed?
* Who owns which subsystems?
* Is there a board of governors or a BDFL or something like that effectively overseeing the whole project?
* What is the process for screening commits from people new to the project?
This whole post seems to be tinged with a bit of defensiveness on behalf of
the most active committers to the project. But it wasn't the active committers
who introduced this most recent bug.
------
dfc
The tor project is a great example of how open source software (OSS) projects
can work with sponsors. Trying to find more information on Qualys and PSW
Groups sponsorship of openssl is a nightmare compared to tor project
sponsors.[^1][^2] Without the tor project's emphasis on transparency and
professionalism I doubt they could post numbers like this:
Since meeting the revenue milestones of $1,253,241 in 2009,
$1,574,119 in 2010 and $1,681,101 in 2011, Tor has reached new
heights in 2012 with over $2 million in revenue (unaudited).[^3]
My comment should not be read as a criticism of OpenSSL, it should be
interpreted as cause for optimism. The tor project has demonstrated that OSS
projects can get sponsored to solve complicated security problems that are
difficult to explain to the general public.
[^1]: List of sponsors/projects:
[https://trac.torproject.org/projects/tor/wiki/org/sponsors](https://trac.torproject.org/projects/tor/wiki/org/sponsors)
[^2]: Example monthly report for SponsorF's project:
[https://lists.torproject.org/pipermail/tor-
reports/2014-Marc...](https://lists.torproject.org/pipermail/tor-
reports/2014-March/000484.html)
[^3]: Tor Project Annual Report 2012, pg 8,
[https://www.torproject.org/about/findoc/2012-TorProject-
Annu...](https://www.torproject.org/about/findoc/2012-TorProject-Annual-
Report.pdf)
------
x0x0
It's well and fine that Stephen lives very cheaply, but all of this is an
attempt to distract from the OpenSSL project's very real issues by wearing a
cilice then bitching about it.
The fundamental facts are these: openssl contains a large quantity of code
that, if I where to check into my company's repo, I would have at best a rough
conversation with the cto and at worst I'd get fired. Plus a lack of good
tests. These combine to create more than hypothetical problems; we've seen
some severe security holes and there's almost certainly more to come.
The question that should be discussed is if openssl is, ala sendmail,
unsuitable for purpose and, if so, what should it be replaced with.
------
runn1ng
Google Cache version (site is 404ing for me)
[http://webcache.googleusercontent.com/search?q=cache:http://...](http://webcache.googleusercontent.com/search?q=cache:http://veridicalsystems.com/blog/of-
money-responsibility-and-pride/&strip=1)
------
wbl
OpenBSD has had two holes in a heck of a long time. By contrast OpenSSL has
had a remote execute in 2010, and another 4 in 2002, and is regularly patching
DOS's resulting from memory corruption that turns out not to be exploitable.
It is 453,000 or so lines, more than five times the size of xv6. It is ten
times as big as PolarSSL. Documentation and internal structuring is wildly
inconsistent. Features that make static analysis annoying are widely used. The
API is far too low level.
Do you believe this is acceptable in a security library? Do believe that
aspiring to the security of qmail or OpenSSH is a reasonable goal, even at the
cost of features? Why should I use OpenSSL for TLS termination when formally
validated alternatives exist?
~~~
wfn
> Why should I use OpenSSL for TLS termination when formally validated
> alternatives exist?
Oh please do share! (spoiler: alternatives which enable side channels because
the pretty compiled-optimized-code (that is generated from source code that
itself may feature immutable data etc. with no side effects) is ripe with
leaks via cpu branching, caching, etc etc do not count.) This is not a
spiteful rhetorical inquiry, by the way!
~~~
AaronFriel
Those side-channel attacks are largely theoretical. OpenSSL and RSA in general
are vulnerable to side channel attacks, because many of the fundamental
operations are not constant-time. That can change eventually, but RSA is
difficult to write in a constant-time manner. OpenSSL certainly has had its
fair of lab-demonstrated side-channel attacks, but I don't think anyone has
been able to demonstrate their use in virtualized hosting environments against
arbitrary other tenants.
Side channel attacks once you've already got code running on the same
operating system as the target are much easier. But if you can get arbitrary
code to execute on the same machine running OpenSSL, you probably already have
their keys.
So, I think the criticism to OpenSSL is valid. Why use it when it seems there
are less bad alternatives? A lot of it comes down to network effects, inertia,
and licensing. That's a much better answer than side-channel attack surface
area, which all RSA implementations share :)
~~~
wbl
Nope: you can exploit the timing attacks from across a network link in AES.
DJB did this long, long ago. Furthermore, I believe OpenSSL has constant-time
RSA, but you can always use ECDSA for which constant time implementations in C
exist. (I wrote one, but I still need to switch the hash function to SHA256
and add the unnecessary encoding steps to the output, so consider it a PoC).
~~~
AaronFriel
Are you sure? Searching for "side channel OpenSSL" reveals a majority of the
attacks are against ECDSA. Of course, searches aren't the best measure of
vulnerability, it's just an indication of popularity.
~~~
wbl
[http://cr.yp.to/antiforgery/cachetiming-20050414.pdf](http://cr.yp.to/antiforgery/cachetiming-20050414.pdf)
ECDSA is nice because you can use partial nonce recovery+lattice reduction.
Furthermore recent Intel chips have AES instructions.
------
piercebot
Reading about Dr. Stephen Henson reminded me of the article written about Tarn
Adams, the creator of Dwarf Fortress.
[http://www.nytimes.com/2011/07/24/magazine/the-brilliance-
of...](http://www.nytimes.com/2011/07/24/magazine/the-brilliance-of-dwarf-
fortress.html?pagewanted=all&_r=0)
------
conductr
Not hard. Just change the license and require commercial use to be paid
|
/*
** 2014 September 22
**
** The author disclaims copyright to this source code. In place of
** a legal notice, here is a blessing:
** May you do good and not evil.
** May you find forgiveness for yourself and forgive others.
** May you share freely, never taking more than you give.
*/
package info.ata4.util.collection;
import java.util.ArrayList;
import java.util.Collection;
import java.util.Collections;
import java.util.Iterator;
import java.util.List;
import java.util.Objects;
import java.util.Spliterator;
import java.util.Spliterators;
import java.util.function.Consumer;
/**
*
* @author Nico Bergemann <barracuda415 at yahoo.de>
* @param <T>
*/
public class Node<T> implements Collection<Node<T>> {
private T data;
private Node<T> parent;
private final List<Node<T>> children = new ArrayList<>();
public Node() {
}
public Node(T data) {
this.data = data;
}
public Node(Collection<Node<T>> children) {
if (children != null) {
this.children.addAll(children);
}
}
public Node(T data, Collection<Node<T>> children) {
this.data = data;
if (children != null) {
this.children.addAll(children);
}
}
public T data() {
return data;
}
public void data(T data) {
this.data = data;
}
public Node<T> parent() {
return parent;
}
private void parent(Node<T> parent) {
this.parent = parent;
}
public void forEachData(Consumer<T> action) {
Objects.requireNonNull(action);
action.accept(data());
children.forEach(node -> node.forEachData(action));
}
@Override
public int size() {
return children.size();
}
@Override
public boolean isEmpty() {
return children.isEmpty();
}
@Override
public boolean contains(Object o) {
return children.contains(o);
}
@Override
public Iterator<Node<T>> iterator() {
return Collections.unmodifiableList(children).iterator();
}
@Override
public Spliterator<Node<T>> spliterator() {
return Spliterators.spliterator(Collections.unmodifiableList(children),
Spliterator.ORDERED | Spliterator.IMMUTABLE);
}
@Override
public Object[] toArray() {
return children.toArray();
}
@Override
public <T> T[] toArray(T[] a) {
return children.toArray(a);
}
@Override
public boolean add(Node<T> node) {
boolean added = children.add(node);
if (added) {
node.parent(this);
}
return added;
}
@Override
public boolean remove(Object o) {
boolean removed = children.remove(o);
if (removed) {
((Node<T>) o).parent(null);
}
return removed;
}
@Override
public boolean containsAll(Collection<?> c) {
return children.containsAll(c);
}
@Override
public boolean addAll(Collection<? extends Node<T>> c) {
boolean added = children.addAll(c);
if (added) {
forEach(node -> node.parent(this));
}
return added;
}
@Override
public boolean removeAll(Collection<?> c) {
List<Node<T>> childrenOld = new ArrayList<>(children);
boolean removed = children.removeAll(c);
if (removed) {
childrenOld.removeAll(children);
childrenOld.forEach(node -> node.parent(null));
}
return removed;
}
@Override
public boolean retainAll(Collection<?> c) {
List<Node<T>> childrenOld = new ArrayList<>(children);
boolean retained = children.retainAll(c);
if (retained) {
childrenOld.removeAll(children);
childrenOld.forEach(node -> node.parent(null));
}
return retained;
}
@Override
public void clear() {
children.clear();
}
@Override
public int hashCode() {
int hash = 5;
hash = 43 * hash + Objects.hashCode(this.data);
hash = 43 * hash + Objects.hashCode(this.children);
return hash;
}
@Override
public boolean equals(Object obj) {
if (obj == null) {
return false;
}
if (getClass() != obj.getClass()) {
return false;
}
final Node<?> other = (Node<?>) obj;
if (!Objects.equals(this.data, other.data)) {
return false;
}
if (!Objects.equals(this.children, other.children)) {
return false;
}
return true;
}
}
|
Grilled Fish Steaks
Prepare flavored butter of your choice.
Set aside.
Rinse fish, pat dry, and rub with oil.
Place on a lightly greased grill 4 to 6 inches above a solid bed of hot coals.
Cook, turning once or twice, until fish is just opaque or tuna is slightly pink but still moist in thickest part; cut to test 8 to 10 minutes.
Season fish to taste with salt and pepper; offer flavored butter to spoon over individual portions. |
Introduction
============
Polyphenols are one of the largest and widely natural products distributed in plant cells, since more than 10,000 phenolic compounds have been described so far in higher plants, with several 100 found in edible plants ([@B31]; [@B46]; [@B26]). Flavonoids (Latin flavus, "yellow") represent 60% of these polyphenols and cover more than 6000 compounds ubiquitously distributed in plants ([@B8]; [@B14]).
All flavonoids have a generic chemical structure consisting of 15 carbon atoms (C6-C3-C6): two aromatic rings (rings A and B) connected by a heterocyclic pyran C which contains one oxygen (ring C, **Figure [1](#F1){ref-type="fig"}**) ([@B19]; [@B47]; [@B27]; [@B39]; [@B11]). This basic skeleton can have multiple substituents, as hydroxyl groups as well as sugars ([@B9]). Depending on the pattern of hydroxylation and the substituents on the heterocyclic ring C, flavonoids can be classified into several sub-groups, but in this paper we focus on two groups: flavones as luteolin (present in Thai chili, broccoli and leaves of onion and celery) and apigenin (present in parsley, celery, onion, garlic, red pepper, and chamomile tea); and flavanones (as eriodictyol found in citrus fruits such as orange, lemon, or grapefruit) ([@B31]; [@B46]; [@B27]).
{#F1}
The biological activities of these compounds depend both on their structural differences and glycosylation patterns ([@B19]; [@B46]). In fact, diet flavonoids can promote health and prevent certain diseases such as cancer by acting against cell oxidation processes and by stopping cell degradation and aging ([@B30]).
The effects of flavonoids in humans can be attributed to antioxidant, antitumor, anti-inflammatory, antimicrobial, anticancer, and cardiovascular actions. For example, eriodictyol performs a key role against the pathogenesis of diabetes mellitus, inhibiting immunoglobulin E/antigen-produced type I hypersensitivity. This flavanone also shows antinociceptive, hyperthermic, and anticancer effects ([@B53]). Apigenin has a growing importance due to its inhibitory effect on the PI3K/Akt/mTOR signaling pathways ([@B43]). Luteolin is able to inhibit angiogenesis or to reduce tumor size *in vivo* since it is able to modulate protein kinases and growth factor receptors as EGFRs or VEGFRs ([@B29]). Also, the antioxidant capacity of these and other polyphenols acts as master key in preventing numerous diseases associated with oxidative damage such as cardiovascular, neurodegenerative and cancer ([@B39]; [@B15]).
Flavonoids are synthesized *in planta* by the phenylpropanoid pathway, which converts L-Phe in 4-coumaroyl-CoA in three steps, the common intermediate for all flavonoids (**Figure [1](#F1){ref-type="fig"}**) ([@B10]). These first three common steps are catalyzed by phenylalanine ammonia lyase (PAL), cinnamate 4-hydroxylase (4CH) and 4-coumaroyl CoA ligase (4CL) (**Figure [1](#F1){ref-type="fig"}**). Then the chalcone synthase (CHS) condenses a molecule of 4-coumaroyl-CoA with three molecules of malonyl-CoA, generating naringenin chalcone, the basic skeleton for all flavonoids ([@B46]; [@B48]; [@B10]). The heterocycle C closure is catalyzed by chalcone isomerase (CHI), which generates naringenin, the precursor for apigenin and luteolin (flavones) and for eriodictyol (flavanone). In order to generate apigenin, the flavone synthase (FNS) oxidoreductase is required. Apigenin is then the substrate for the flavonoid 3′-hydroxylase (F3′H), giving rise to luteolin (**Figure [1](#F1){ref-type="fig"}**). On the other hand, naringenin is also the substrate for F3′H, generating eriodictyol without FNS activity (**Figure [1](#F1){ref-type="fig"}**) ([@B9]).
Flavonoids are valuable compounds for use in the pharmaceutical, chemical and nutraceutical industry, but the amounts that can be obtained directly from plants are very limited. One solution is the chemical synthesis, but when dealing with metabolites with complex chemical structures, their production is economically not feasible in most cases. Therefore, an attractive alternative is to express these plant biosynthetic gene pathways in microbial factories, using combinatorial biosynthesis, where genes from different organisms are grouped in an artificial gene cluster directed to the production of the natural bioactive compound ([@B10]; [@B45]). Microorganisms that are most commonly used as cell factories for flavonoids are *Saccharomyces cerevisiae, Escherichia coli* and in some cases *Streptomyces venezuelae*, where different techniques are applied in order to increase production levels.
However, in the last years, focus has been made in *de novo* processes for flavonoids microbial production, without adding expensive precursors to the culture medium, therefore allowing cheap production platforms necessary for broad commercial use of flavonoids as nutraceuticals ([@B13]; [@B48]; [@B50]). In this work, we have achieved *de novo* production of apigenin, luteolin, and eriodictyol by means of synthetic biosynthetic pathways heterologous expressed in *Streptomyces albus.* The use of Gram-positive bacterial factories, as this actinomycete, facilitates the further industrialization of bioactive compounds for the pharmaceutical industry, as on the one hand, actinomycetes are the most diverse and rich producers of bioactive compounds (antibacterials, antifungals, antitumors, herbicides, immunosuppressors, etc.), belonging to many different biochemical families (lactams, polyketides, non-ribosomal peptides, terpenoids, flavonoids, etc.), and providing all the necessary metabolic precursors and biosynthetic machinery for these purposes, including also all post-translationally modification enzymes ([@B34]). Actually, about two thirds of all known bioactive polyketides are produced by actinomycetes. This huge biosynthetic capability is accompanied also by a huge diversity in resistance mechanisms to allow production of such a wide range of bioactive compounds ([@B52]; [@B17]). This role as useful bacterial factories for bioactives is reinforced in the case of some actinomycetes as *Saccharopolyspora erythraea, S. coelicolor, S. lividans, S. avermitilis, S. venezuelae* and *S. albus*, as their genomes have been sequenced and multiple genetic manipulation tools are available for them. Specifically, in the case of *S. albus*, this host is more convenient as it shows a fast and nice disperse mycelial growth, instead of the most common mycelial dense aggregates shown in the case of other actinomycetes. This disperse growth facilitates scaling-up at industrial bioreactors, as less complications arise from local cellular density and cell lysis. Also, *S. albus* can be transformed with methylated plasmid DNA, in contrast to other actinomycetes, which also facilitates genetic engineering in this species ([@B18]).
Materials and Methods {#s1}
=====================
Bacterial Strains, Plasmids, and Culture Conditions
---------------------------------------------------
*Escherichia coli* TOP10 (Invitrogen) and pUC57 (Fermentas) were used for routine sub-cloning. The high-copy number shuttle vector pIAGO (**Table [1](#T1){ref-type="table"}**) for *E. coli*--*Streptomyces*, which contains the strong constitutive *ermE* promoter P~ermE^∗^~ ([@B1]), was used as expression plasmid in the strain *S. albus* J1074 ([@B7]), which was used as host for the production of flavones and flavanones (**Table [2](#T2){ref-type="table"}**).
######
List of plasmids used in this study.
Plasmid Description Source
---------- ------------------------------------------------------- ------------
pIAGO pWHM3 (replicative shuttle vector) harboring permE^∗^ [@B1]
pSL1180 *E. coli* vector [@B4]
pUC57 *E. coli* vector Fermentas
pLMF1 pUC57 harboring TAL This study
pLMF2 pUC57 harboring 4CL This study
pLMF3 pUC57 harboring CHS This study
pLMF5 pUC57 harboring CHI This study
pLMF-FNS pUC57 harboring FNS This study
pLMF7 pSL1180 harboring TAL This study
pLMF8 pSL1180 harboring TAL and 4CL This study
pNGM1 pSL1180 harboring CHS and FNS This study
pNGM2 pSL1180 harboring TAL, 4CL, CHS, and FNS This study
pNGM3 pSL1180 harboring TAL, 4CL, CHS, FNS, and CHI This study
pAPI pIAGO harboring TAL, 4CL, CHS, FNS, and CHI This study
pNGM4 pSL1180 harboring TAL, 4CL, CHS, F3′H, and CHI This study
pERI pIAGO harboring TAL, 4CL, CHS, F3′H, and CHI This study
pNGM5 pSL1180 harboring TAL, 4CL, CHS, FNS, CHI, and F3′H This study
pLUT pIAGO harboring TAL, 4CL, CHS, FNS, CHI, and F3′H This study
######
List of strains used in this study.
Strains Description Source
---------------------------- ---------------------------------------------------------------------- ------------
*E. coli* TOP10 Strain used for routine sub-cloning and transformation in *S. albus* Invitrogen
*Streptomyces albus* J1074 Strain used to create the flavonoid-producing mutants [@B7]
*S. albus*-pIAGO *S. albus* harboring pIAGO used as negative control This study
*S. albus*-pAPI *S. albus* harboring pAPI This study
*S. albus*-pERI *S. albus* harboring pERI This study
*S. albus*-pLUT *S. albus* harboring pLUT This study
*Escherichia coli* was grown at 37°C in TSB liquid broth or TSB agar (VWR), supplemented with the corresponding antibiotics for plasmid selection (ampicillin 100 μg/ml, Sigma Aldrich). *S. albus* J1074 was grown at 30°C in YEME 17% sucrose ([@B18]) for the preparation of protoplasts. It was sporulated on Bennet medium ([@B18]), and supplemented with the corresponding antibiotics when necessary (thiostrepton 50 μg/ml, Sigma Aldrich).
For flavonoids production, *S. albus* clones were grown in 25 ml of R5A medium ([@B12]), supplemented with the corresponding antibiotic, during 184 h (96 h for feeding experiments) at 30°C and at 250 rpm. Spores were previously quantified and an inoculum of 10^7^ spores/ml was used always as inoculum.
DNA Manipulation
----------------
Restriction enzymes were purchased from Takara Biochemicals, T4 DNA ligase, Klenow fragment and Dream Taq DNA Polymerase from Thermo Scientific. Synthetic genes for the following ORFs (EBI preliminary accession number [Hx2000056376](Hx2000056376)) were generated by Genecust after codon optimization: TAL (as *Bgl*II-*Pst*I gene cassette) from *Rhodobacter capsulatus* (GenBank accession no. WP_013066811), 4CL (as *Pst*I-*Sac*I gene cassette) from *S. coelicolor* (GenBank accession no. NP_628552), CHS (as *Sac*I-*Eco*RI gene cassette) from *Glycine max* (GenBank accession no. L07647.1), CHI (as *Xba*I*-Eco*RV gene cassette) from *G. max* (GenBank accession no. AY595413.1), FNS (as *Eco*RI-*Xba*I gene cassette) from *Petroselinum crispum* (GenBank accession no. AY230247.1) and F3′H (as *Eco*RV-*Bam*HI gene cassette) from *Arabidopsis thaliana* (GenBank accession no. Q9SD85). Compatible restriction sites were added at each gene cassette end, in order to facilitate construction of the recombinant flavonoids gene clusters, as well as ribosome binding sites at the 5′-ends.
All constructed plasmids (**Figure [1](#F1){ref-type="fig"}**) described below were verified by restriction enzymes digestions and also by sequencing of the cloned regions. *S. albus* producing clones were confirmed by PCR by the use of oligonucleotides designed to amplify the junction site at the first two common genes (TAL and 4CL): 5′-GTGATCGAGCTGGACATGAA-3′ as the forward primer and 5′-GGCGTCCACGAGGTGC-3′ as the reverse primer.
Construction of pAPI
--------------------
The plasmid pAPI is a pIAGO derivative (**Table [1](#T1){ref-type="table"}**) containing the P~ermE^∗^~ and the five genes responsible for apigenin *de novo* biosynthesis. All synthetic gene cassettes were independently cloned in pUC57 and those plasmids were named pLMF1 (pUC57 containing TAL gene), pLMF2 (4CL), pLMF3 (CHS), pLMF5 (CHI), and pLMF-FNS (FNS). Additionally, TAL gene was subcloned into vector pSL1180 as *Hind*III-*Bam*HI (pLMF7) to start with the cloning strategy. 4CL gene (from pLMF2) was cloned into pLMF7 as *Pst*I-*Bam*HI gene cassette, generating pLMF8. Next step was subcloning FNS gene cassette from pLMF-FNS into pLMF3 as an *Eco*RI-*Xba*I DNA fragment, giving rise to pNGM1. The two gene cassettes from pNGM1 (CHS and FNS) were subcloned together into pLMF8 as *Sac*I-*Bam*HI DNA band, in order to get the first four genes together in a plasmid (pNGM2). Finally, CHI gene was subcloned into pNGM2 as *Xba*I-*Bam*HI DNA fragment resulting in the generation of pNGM3, which contains the five genes required for apigenin biosynthesis.
As the expression host was *Streptomyces*, a further subcloning was required, and the *Bgl*II-*Bam*HI DNA fragment from pNGM3 carrying these five genes was finally subcloned into a derivative of the bifunctional replicative vector pIAGO, under the control of P~ermE^∗^~, giving rise to the final plasmid pAPI.
Construction of pLUT
--------------------
The plasmid pLUT (**Table [1](#T1){ref-type="table"}**) directs the biosynthesis of luteolin and contains the six required genes (TAL, 4CL, CHS, CHI, FNS, and F3′H), as well as the P~ermE^∗^~. This plasmid requires only one more gene (F3′H) than those ones present in pAPI. Therefore, pNGM3 was used for the construction of pLUT. The gene cassette F3′H was subcloned into pNGM3 as an *Eco*RV-*Bam*HI DNA fragment. This plasmid was named pNGM5 and contains all six genes. These genes were further subcloned as a *Bgl*II-*Bam*HI DNA fragment into the pIAGO vector, in order to achieve expression in *S. albus*, giving rise to plasmid pLUT.
Construction of pERI
--------------------
The plasmid pERI (**Table [1](#T1){ref-type="table"}**) contains the P~ermE^∗^~ and the five genes required for the biosynthesis of eriodictyol. These genes are the ones encoding for TAL, 4CL, CHS, CHI, and F3′H. As all the genes but the one coding for FNS are the same ones required to produce luteolin, the construction of the plasmid directing the biosynthesis of eriodictyol was based on the previously described plasmid, pNGM5. This plasmid was digested with *Eco*RI-*Xba*I, and then blunt-ended with Klenow fragment, to eliminate the gene cassette FNS. This new pSL1180 derivative plasmid was named pNGM4. In order to express these five genes in *S. albus*, they were subcloned in the replicative vector pIAGO as a *Bgl*II-*Bam*HI DNA fragment, giving rise to the final plasmid, pERI.
Extraction and Analysis of Flavonoids
-------------------------------------
Spores from the different *S. albus* J1074 recombinant clones harboring pAPI, pERI, pLUT, and pIAGO (negative control) were incubated during 184 h in 25 ml of liquid production medium R5A. Flavonoids extraction was carried out using three volumes of ethyl acetate and extracting separately the supernatant and the disrupted mycelium pellet (after acetone treatment). These extraction mixtures were incubated for 1 h in orbital shaker at room temperature. After this incubation, the organic phases were filtered, mixed together and concentrated by rotary evaporation and kept at -20°C for later use. All cultivation experiments were carried out three times for each strain or analysis.
Dry extracts were dissolved in 200 μl of methanol:DMSO (1:1), filtrated (0.4 μm cellulose filters) and analyzed by liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS/MS, Agilent technologies 1290 Infinity, Triple Quadrupole). This chromatography was carried out using a Zorbax Eclipse Plus C18 column (50 mm × 2.1 mm, 1.8 μm) in the positive ion mode. The analytes were eluted at a flow rate of 0.3 mL/min using a gradient of 0.1% (v/v) formic acid in water (A) and 0.1% (v/v) formic acid in acetonitrile (B) at 0--10% of B for 1 min, which was increased to 35% for 3 min and maintained at 35% for 1 min; then increased to 80% for 3 min and maintained at 80% for 2 min and finally decreased to 10% for 1 min.
Flavonoids quantification was carried out in multiple reaction monitoring (MRM) mode in MS/MS. To accomplish this, the following ion sets were selected to detect the transitions of the parent ions to the product ions specific to the analytes: naringenin 272 \> 119 Da and 272 \> 151 Da; apigenin 270 \> 117 Da and 270 \> 150 Da; eriodictyol 288 \> 135 Da and 288 \> 150 Da; luteolin 286 \> 131 Da and 286 \> 151 Da. Pure flavonoid standards were purchased from Sigma Aldrich (apigenin, eriodictyol, naringenin) and VWR (luteolin).
Spore Conditioning Experiments
------------------------------
Spore conditioning was carried out by incubating during 10 days a suspension of 10^8^ or 10^9^ spores/mL in 5 mL R5A medium, at 30°C and 250 rpm, in 50 mL Falcon tubes (final spore concentrations of 10^5^ and 10^6^ spore equivalent/mL respectively). This incubation was carried out in order to force spore germination in a high density culture, which induces programed cell death in mycelium I (MI), releasing the developmental signals that induce the differentiation (conditioning) of the MI cellular segments that remained viable into a new mycelium (MII), that is the secondary metabolite producer ([@B32]). Due to the high density, this conditioned mycelium (MII), cannot growth too much, and remains quiescent until it is inoculated into a fresh medium ([@B32]).
Thirty μL of the conditioned cultures (equivalent to 3 × 10^6^ or 3 × 10^7^ spores) were inoculated in 25 mL R5A medium in a 250 mL buffled flask (triplicates). As a control, simultaneously, other flask triplicates with 25 mL R5A medium were inoculated with our standard conditions, 30 μL of a spore stock solution (at 10^10^ spores/mL), which represents a final spore concentration in the flasks of 10^7^ spores/mL All these nine flasks were incubated at 30°C and 250 rpm during 168 h, and samples were taken every 24 h: 20 μL samples for confocal microscopy; 180 μL samples for protein quantification using the Bradford method ([@B3]) after boiling in 0.5 M NaOH for 10 min and after removing cellular debris by centrifugation (at 7740 × *g* for 15 min); and 1.5 mL for apigenin extraction and HPLC--MS quantification.
Feeding Experiments
-------------------
Two hundred and fifty ml Erlenmeyer flasks with 25 mL R5A medium were inoculated with 10^7^ spores/mL of *S. albus*-pAPI and incubated at 30°C and 250 rpm during 48 h, according with previous literature ([@B37]). At this time point, amounts of different precursors were added to achieve final concentrations of 1.2 mM *p*-coumaric acid, 13.5 mM sodium malonate, 1.2 mM *p*-coumaric acid plus 13.5 mM sodium malonate, or 0.1 mM naringenin in the corresponding flasks (triplicates). 1.5 mL of each culture was extracted at 96 h, as described in Section "Extraction and Analysis of Flavonoids," and apigenin was quantified by HPLC--MS. These final precursors concentrations were selected based in literature ([@B37], [@B36]).
Laser Scanning Fluorescence Microscopy
--------------------------------------
*Streptomyces albus* cultures from 24 h until 96 h were stained using the LIVE/DEAD BacLight Bacterial Viability Kit (Invitrogen), and observed under a Leica TCS-SP2-AOBS laser scanning microscope at wavelengths of 488 and 568 nm for excitation and 530 and 630 nm emission (optical sections of about 0.2 μm). Images were mixed with the Leica Confocal Software. In these conditions, living mycelium appears green colored (SYTO9 staining), while dying mycelium appears red (PI staining). Septa are visible as discontinuities in the SYTO9/PI stained hyphae; MI is fully compartmentalized, while MII (the secondary metabolite producer mycelium) is multinucleated with sporadic septa ([@B32]).
Results
=======
Heterologous Production of Apigenin
-----------------------------------
The flavone apigenin is generated due to the action of the enzyme FNS (flavone synthase) on the important flavonoid precursor naringenina (**Figure [1](#F1){ref-type="fig"}**). In order to produce the plant metabolite naringenin in microorganisms, four enzymes are required: TAL, 4CL, CHS, and CHI (**Figure [1](#F1){ref-type="fig"}**). Four synthetic genes coding for these enzymes (adapted to the transcription and translation characteristics in prokaryotes as *S. albus*), together with a synthetic gene coding for FNS, were cloned in a replicative high-copy number shuttle vector for *E. coli--Streptomyces*, under the control of P~ermE^∗^~ (see Materials and Methods). The final plasmid construction, pAPI, was transformed and successfully expressed in the actinomycete *S. albus*, as a method to achieve future industrial production of this important flavonoid.
Cultures of *S. albus*-pAPI in R5A liquid medium were analyzed by HPLC--MS chromatography in MRM in MS/MS mode, in order to identify and quantify the final product, apigenin, as well as its intermediate precursors naringenin and *p*-coumaric acid (**Figure [1](#F1){ref-type="fig"}**). *p*-Coumaric acid is the second common metabolite in flavonoids biosynthesis, after transformation of the initial aromatic amino acid precursor in plants (L-Phe) or in microorganisms (L-Tyr) (**Figure [1](#F1){ref-type="fig"}**). The three compounds (*p*-coumaric acid, naringenin, and apigenin) were detected in these analyses and their yields were quantified using commercial pure standards (see Materials and Methods). Production rates for apigenin synthetized by *S. albus*-pAPI were 0.08 mg/L. Its precursor naringenin was produced at lower level (0.014 mg/L), and the *p*-coumaric acid initial precursor for this pathway was observed at higher concentration, reaching levels of 0.774 mg/L (**Figure [2](#F2){ref-type="fig"}**). Negative control strain harboring the empty vector, *S. albus*-pIAGO showed no flavonoids in their HPLC--MS analyses.
{#F2}
Differentiation of a multinucleated mycelium (MII) conditions secondary metabolism production ([@B32]). Consequently, we tested the possibility to further improve apigenin production levels, or even anticipate time of maximum production, as a way to save money in future industrial fermentations, based in the improvement of the MII differentiation. Spore conditioning experiments were carried out with *S. albus*-pAPI (see Materials and Methods). Briefly, germination in dense spore inocula force programed cell death in the vegetative MI, releasing the developmental signals that induce the differentiation (conditioning) of the MI cellular segments that remained viable into a new mycelium (MII, secondary metabolite producer). Due to the high density, this conditioned mycelium (MII) remains quiescent until it is inoculated into a fresh medium ([@B32]). Conditioning times longer that these 10 days did not show extra advantages with respect to final effect in generation of quiescent MII. Also, after these 10 days, the obtained mycelium II remains quiescent and conditioned during a long time (at least months), ready to be used in different production batches ([@B32]). Development and apigenin production were compared in cultures inoculated with conditioned and non-condtioned spores (**Figures [3](#F3){ref-type="fig"}, [4](#F4){ref-type="fig"}**). These experiments showed that inocula from conditioned cultures contained high amounts of dead mycelium pellets (red staining), non-germinated spores, and quiescent MII (green staining) (**Figure [3B](#F3){ref-type="fig"}**). By contrast, control cultures (non-conditioned inocula) contained only spores (**Figure [3A](#F3){ref-type="fig"}**). After 24 h incubation, control flasks showed normal development toward MI (**Figure [3A](#F3){ref-type="fig"}**), whereas conditioned flasks at this point showed a high proportion of producing MII (**Figure [3B](#F3){ref-type="fig"}**). Control flasks did not show a high proportion of MII until 72 h (**Figure [3A](#F3){ref-type="fig"}**). Accordingly, apigenin production was faster and the maximum production levels earlier in conditioned flasks (72 h for 10^6^ conditioned spore equivalent/mL flasks and 96 h for 10^5^ conditioned spore equivalent/mL flasks) than in the control flasks (120 h, 10^7^ spores/mL) (**Figure [4](#F4){ref-type="fig"}**).
{#F3}
{#F4}
Finally, in order to try to increase apigenin final production titers, feeding experiments were carried out (**Figure [5](#F5){ref-type="fig"}**). Feeding with coumaric acid, sodium malonate or both together did not increased significantly final apigenin titers (0.139, 0.106, and 0.159 mg/L apigenin; in contrast to 0.082 mg/L in control without feeding). However, feeding with 0.1 mM naringenin caused a statistically significant increase in apigenin production levels, achieving 0.384 mg/L.
{#F5}
Heterologous Production of Eriodictyol
--------------------------------------
The flavanone eriodictyol is a hydroxylated form of the flavanone precursor naringenin. For its biosynthesis, only one extra enzymatic activity is required, the F3′H (flavonoid 3′-hydroxylase) at ring B (**Figure [1](#F1){ref-type="fig"}**), instead of the FNS oxidoreductase. Final replacement in pAPI plasmid of the gene cassette coding for FNS by the new one coding for F3′H generated a vector containing the five genes (TAL, 4CL, CHS, CHI, and F3′H) required for eriodictyol biosynthesis in *S. albus* under the control of P~ermE^∗^~ (see Materials and Methods).
This new recombinant plasmid, pERI, was transformed in *S. albus* protoplasts, and cultures from positive recombinant strains (in R5A liquid medium) were analyzed by MRM chromatography. These experiments demonstrated that recombinant plasmid pERI was able to redirect the biosynthesis from apigenin to eriodictyol in *S. albus*, using as common precursor the naringenin already detected in previous experiments. However, production levels for eriodictyol in these extracts were very low under these conditions (0.002 mg/L). However, higher levels of the naringenin precursor (0.037 mg/L) were observed. The initial precursor *p*-coumaric acid was also analyzed, showing production levels of 1.256 mg/L (**Figure [2](#F2){ref-type="fig"}**).
Heterologous Production of Luteolin
-----------------------------------
Luteolin biosynthesis in microorganisms requires the activity of six enzymes: TAL, 4CL, CHS, CHI, FNS, and F3′H. The genes coding for these enzymes were cloned in the same replicative high-copy number shuttle vector for *E. coli--Streptomyces* (see Materials and Methods), under the control of the promoter P~ermE^∗^~, generating the final plasmid pLUT. This plasmid was transformed into *S. albus* protoplasts.
Clones of this recombinant strain were cultivated in R5A liquid medium and flavonoids productivity was quantified using HPLC--MS in their extracts. Luteolin was detected with production rates of 0.09 mg/L) but its precursor apigenin was observed at higher levels (0.085 mg/L) (**Figure [2](#F2){ref-type="fig"}**). As in previous experiments, a higher accumulation of the initial precursor *p*-coumaric acid was detected (0.872 mg/L).
Discussion
==========
In this work, *S. albus* has been able to *de novo* biosynthetize four flavonoids: naringenin (a flavanone precursor in this family of nutraceuticals), apigenin (its oxidized flavone derivative), luteolin (a 3′-hydroxylated apigenin) and eriodictyol (a 3′-hydroxylated version of the flavanone naringenin).
*De novo* naringenin production has been previously described in recombinant strains of *E. coli* ([@B16]; [@B33]; [@B42])*, S. cerevisiae* ([@B51]; [@B44]), and *S. clavuligerus* ([@B2]). Other authors also achieved its production in other microorganisms, but after feeding with precursors ([@B37]).
Apigenin was previously produced *de novo* only in *E. coli* ([@B33]). Here, the complete biosynthetic pathway was cloned in *E. coli* and production levels reached up to 13 mg/L. However, the addition to culture medium of the main precursor L-tyrosine at 543 mg/L (3 mM) was required ([@B33]) (**Table [3](#T3){ref-type="table"}**). In a more recent work, apigenin yields were increased to 23 mg/L in *E. coli*. But, as in the work developed by [@B33], its synthesis needed the supplementation with *p*-coumaric acid ([@B20]). Higher production levels in *E. coli*, 110 mg/L, have been described after feeding with *p*-coumaric acid and malonate ([@B23]). This flavone was also produced in *S. venezuelae* at 1.5 mg/L, but only after feeding with 0.5 mM (136 mg/L) naringenin a *S. venezuelae* strain which contained only the gene coding for FNS oxidoreductase ([@B36]) (**Table [3](#T3){ref-type="table"}**).
######
List of heterologous microbial hosts for biosynthesis of flavanones and flavones in the literature and estimated production titers.
Heterologous flavonoid produced Host Externally fed precursor Production titers (mg/L) Reference
--------------------------------- ----------------- -------------------------------- -------------------------- -----------
Apigenin *E. coli* L-Tyrosine 13 [@B33]
*E. coli* *p*-Coumaric acid 23 [@B20]
*S. venezuelae* Naringenin 1.5 [@B36]
*S. venezuelae* *p*-Coumaric acid 15.3 [@B35]
*S. cerevisiae* *p*-Coumaric acid 3.5 [@B25]
*E. coli* *p*-Coumaric acid and malonate 110 [@B23]
Eriodictyol *E. coli* Caffeic acid 0.03 [@B24]
*E. coli* L-Tyrosine 107 [@B54]
*S. cerevisiae* Caffeic acid 6.5 [@B51]
*S. cerevisiae* Caffeic acid 20 [@B25]
*E. coli* *p*-Coumaric acid and malonate 50 [@B23]
Luteolin *S. cerevisiae* Caffeic acid 2 [@B25]
*E. coli* *p*-Coumaric acid and malonate 4 [@B23]
In this work, however, the complete biosynthetic pathway for apigenin was heterologous expressed in *S. albus*. Besides, it was not supplemented with any precursor, although the levels of apigenin obtained (0.089 mg/L) were smaller than in other previously described works. Only small amounts (0.001 mg/L) of its immediate precursor naringenin were detected, indicating that the activity of the plant oxidoreductase enzyme FNS is good in this microorganism.
In the case of eriodictyol, according to the literature, its biosynthesis in actinomycetes had not been described before. However, two research groups have reported production of this flavanone in *E. coli* from glucose or after feeding with *p*-coumaric acid plus malonate, caffeic acid or L-tyrosine, reaching production levels of 50, 5.70, 0.02, and 42.6 mg/L respectively ([@B22], [@B23]; [@B54]) (**Table [3](#T3){ref-type="table"}**). In both cases, metabolic engineering in *E. coli* was carried out afterward to enhance the availability of the flavonoids precursor malonyl-CoA, increasing the eriodictyol production levels to 52 and 107 mg/L respectively ([@B22]; [@B54]) (**Table [3](#T3){ref-type="table"}**). In our case, despite the low eriodictyol production levels in *S. albus*, this biosynthesis is *de novo* and has been achieved in an actinomycete for the first time. This low production levels, as well as the accumulation of its precursors naringenin and *p*-coumaric acid, show a low activity for the hydroxylase F3′H (see below).
In the case of the flavone luteolin, its heterologous biosynthesis has been described in *E. coli* (4 mg/L) and *S. cerevisiae* (2 mg/L) after feeding with *p*-coumaric acid plus malonate, or caffeic acid respectively ([@B25], [@B23]) (**Table [3](#T3){ref-type="table"}**). In our case, we demonstrate its *de novo* biosynthesis in *Streptomyces*. Nonetheless, as in the case of eriodictyol, luteolin yields were low. This was expected after the observed eriodictyol results, as luteolin biosynthesis requires also the activity of F3′H hydroxylase (**Figure [1](#F1){ref-type="fig"}**).
These experiments showed that F3′H enzyme in *S. albus* is not able to completely transform naringenin into eriodictyol nor apigenin into luteolin. In *S. albus*-pLUT, no eriodictyol was observed, indicating that the FNS enzyme is quite more efficient than F3′H, as apigenin is detected in higher amounts here than eriodictyol. This idea is supported also by the fact that eriodictyol levels in *S. albus*-pERI were almost 300 times lower than apigenin levels in *S. albus*-pAPI. Other authors have described also that P450 hydroxylases like F3′H from eukaryotic origin may present low solubility in prokaryotic hosts, as in this case *S. albus*, because a membrane anchorage domain may not be suitable in prokaryote systems ([@B35]). The hydroxylase F3′H is a cytochrome P450-dependent monooxygenase which requires its integration into the membrane of the endoplasmic reticulum of plant cells as well as the presence of a P450-reductase carrying electrons from a donor to a NADPH P450 heme-core complex. Functional expression of these plant membrane-bound enzymes in microorganisms is a challenge due to several factors, such as protein insolubility (prokaryotes do not have endoplasmic reticulum membranes to bound) and cofactor incorporation ([@B5]; [@B6]; [@B13]). It has been shown that microbial expression of this family of enzymes is enhanced by engineering P450 reductases, in a way that these reductases are fused to the corresponding P450-dependent monooxygenase, and the membrane binding domain of these ones is deleted to increase solubility in prokaryotic cytoplasm. Following this strategy, soluble and functional chimeras have been obtained ([@B24]; [@B21]; [@B54]). These reasons for the monooxygenases counterparts could explain the very low F3′H activity shown in this study as shown with the low lutein and eriodictyol levels in *S. albus*. Therefore, these studies in *S. albus* will pave the way in order to conduct further enzyme engineering in this type of enzymes, to achieve higher production titers ([@B54]) (**Table [3](#T3){ref-type="table"}**).
Finally, we have seen accumulation of *p*-coumaric acid in our three producing strains, the second metabolite in the pathway (after TAL activity on L-Tyr), which is common to all flavonoid biosynthetic pathways. *p*-Coumaric acid is converted to coumaroyl-CoA by the action of 4CL enzyme, which requires malonyl CoA to synthetize the corresponding flavonoid (naringenin chalcone in our case, **Figure [1](#F1){ref-type="fig"}**). Malonyl-CoA is therefore a limiting factor in flavonoid production, as it is also precursor for fatty acids biosynthesis ([@B49]). In fact, different authors consider that this influx of malonyl-CoA is the biggest bottleneck in the flavonoids biosynthesis, since three molecules of malonyl-CoA are needed to generate a molecule of eriodityol, apigenin, or luteolin in our case. Basal levels of this metabolite inside cells are relatively low, as it is regularly consumed during fatty acids biosynthesis, so low intracellular malonyl-CoA availability may restrict the efficient production of flavonoids in both *E. coli* and *Streptomyces* strains ([@B42]; [@B38]). Accordingly, diverse described strategies to increase flavonoids yields focused on increasing the intracellular pool of malonyl-CoA by overexpressing the acetyl-CoA carboxylase enzyme complex (ACC) in the host strain ([@B16]; [@B33]; [@B35]; [@B48]). ACC overexpression increased cell concentration malonyl-CoA in a 278% in relation to the *E. coli* wild strain ([@B54]). In our case, with so high intracellular *p*-coumaric acid accumulation in comparison to final flavonoids, we can hypothesize that the reason may be also a low supply of malonyl-CoA, due to its consumption by fatty acids biosynthesis in *S. albus.* However, feeding with pure 13.5 mM sodium malonate final concentration in flasks did not generated a significant increase in production levels. The cause of this may be that initially identified similar genes in *S. albus* chromosome to *matB* (membrane malonate carrier protein) and *matC* (malonyl-CoA synthetase) from *S. coelicolor* counterparts (*sco2443, sco2445*) ([@B35]), actually do carry out other enzymatic functions in *S. albus*, and therefore this bacterium cannot incorporate extracellular sodium malonate toward flavonoids biosynthesis. As this step is the bottleneck in flavonoids biosynthesis, addition of *p*-coumaric acid nor both precursors (*p*-coumaric acid plus sodium malonate) does not increase apigenin final titers (**Figure [5](#F5){ref-type="fig"}**). In order to check if feeding with the precursor naringenin was an alternative for increasing final apigenin levels, 0.1 mM of this flavanone were added to *S. albus*-pAPI cultures, and in this case, apigenin production levels were increased 468% (**Figure [5](#F5){ref-type="fig"}**). Once we have achieved biosynthesis of these four flavonoids in *S. albus*, future metabolic engineering in this actinomycete, where the genome information is available, will be able to increase carbon flux toward malonyl-CoA, most probably leading to higher flavonoids production levels. Also, it will be possible to enhance intracellular production levels for *p*-coumaric acid, or limit at some degree possible catabolism pathways or enzymes affecting these precursors or flavonoid intermediates.
With respect to other heterologous hosts for production of bioactives as flavonoids, actinomycetes as *S. albus*, do possess the same degree of available genetic tools for genome and metabolic engineering, in comparison to *E. coli*, but more suitable and easier genetic tools than in the case of the eukaryote *S. cerevisiae*, which has the disadvantage that two copies for each gene function must be modify. As an extra advantage, the huge genetic and metabolic richness derived from large actinomycetes chromosomes allows these bacteria to possess a high diversity of anabolic and catabolic pathways in charge of providing different precursors needed for heterologous biosynthesis of a wide fan of bioactives, as it has been described in "Introduction" ([@B34]).
With respect to the Gram-negative *E. coli* host, production of nutraceuticals like flavonoids for the pharmaceutical industries is favored in Gram-positives as *S. albus.* The reason for this is that *S. albus*, as a canonical Gram-positive bacterium, lacks the presence of important endotoxins for human cells, as those derived from *E. coli* outer membrane. Industrial removal of these lipopolysaccharide toxins involves costly procedures ([@B28]).
As an actinomycete, *S. albus* shows has a complex cell cycle that can be modified in order to further increase production yields of secondary metabolism heterologous bioactives. Secondary metabolism is activated during the MII stage ([@B32]). In this work, we have carried out *de novo* production of apigenin in *S. albus*-pAPI strain by using three alternative cultivation approaches, with and without spore conditioning ([@B32]). It is noticeable that similar production levels were obtained in conditioned and not conditioned cultures, but production was anticipated up to 2 days in the conditioned cultures, even with a delayed growth during the first 24-h. Consequently, conditioned cultures can be useful to manipulate production rates in eventual *S. albus* industrial fermentations, as it was reported in other streptomycetes ([@B41]; [@B40]).
Author Contributions
====================
LM and IG-d-R were involved in creation of the different recombinant plasmids and heterologous production strains. CV and FL were supervisors of these experiments. PY and AM contributed to the perform conditioning experiments. FL is principal investigator of the research project were these experiments were planned.
Conflict of Interest Statement
==============================
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
**Funding.** Authors wish to thank the Spanish Ministry of Economy and Competitiveness (MINECO, for financial support via Grant AGL2010-20622), and also to the Government of the Principality of Asturias (program PCTI for a Technology Transfer Grant).
Authors wish to thank Sergio Cueto, Ph.D., from Servicios Científico-Técnicos at the University of Oviedo, for his help with HPLC chromatography and purification of compounds.
[^1]: Edited by: *Robert Kourist, Graz University of Technology, Austria*
[^2]: Reviewed by: *Hugo Gramajo, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina; Loreto Parra, Pontificia Universidad Católica de Chile, Chile*
[^3]: This article was submitted to Microbiotechnology, Ecotoxicology and Bioremediation, a section of the journal Frontiers in Microbiology
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La municipalità di Gerusalemme ha dato il via libera alla costruzione di 566 unità abitative in tre quartieri di Gerusalemme Est. I permessi di costruzione erano stati congelati su richiesta del premier israeliano, Benjamin Netanyahu, dopo la risoluzione del Consiglio di Sicurezza dell’Onu contro gli insediamenti nei Territori occupati. Ma ora sono stati scongelati, anche alla luce della nuova Amministrazione americano.
La decisione arriva due giorni dopo il giuramento del nuovo presidente Donald Trump e alla vigilia del primo colloquio, stasera la telefono, fra il nuovo leader statunitense e Netanyahu. Fonti governativa hanno fatto sapere al quotidiano Haaretz che il premier israeliano chiederà a Trump di rinegoziare l’accordo con l’Iran e illustrerà la sua proposta per risolvere il conflitto con i palestinesi.
Netanyahu vuol concedere la condizione di “state-minus”, cioè un gradino sotto l’indipendenza totale. Un’autonomia molto ampia su una parte della Cisgiordania occupata. Nei giorni scorsi il Likud, il partito del premier, aveva presentato un piano che prevedeva di concedere ai palestinesi il 39 per cento dei Territori.
Per Netanyahu il momento è favorevole. Trump ha promesso di spostare l’ambasciata statunitense a Gerusalemme, un gesto che indica il riconoscimento di fatto della Città Santa come capitale di Israele. I palestinesi hanno reagito all’offensiva con una accordo fra Al-Fatah, il partito del presidente Abu Mazen, e Hamas, il movimento islamista che governa la Striscia di Gaza, dopo dieci anni di guerra intestina. Ma il nuovo governo di unità deve ancora vedere la luce e le divisioni restano nettissime. |
Kelowna's mayor says a new bylaw cracking down on people sitting, lying or sleeping on city sidewalks is not a crackdown on the homeless.
City council gave initial approval Monday to the bylaw, which extends the hours in which such activity is forbidden. Previously, the practice was only enforceable during business hours. Now, under the new bylaw, it's 24/7.
"Yes, in isolation, it might look like, boy that cruel city council is kicking a person while they're down," says Mayor Colin Basran.
"Not recognizing we have hired a social issues manager to come up with a strategy, in partnership with social agencies and committed organizations in our community. Enforcement is one aspect of a multi-faceted strategy to deal with homeless issues."
Basran says the bylaw, which updates a 20 or 30-year-old statute, gives bylaw officers more tools to work with.
When they do get a complaint, he said, they have the tools to deal with it throughout the day and night.
In explaining the change, bylaw manager Greg Wise says, since the original bylaw was written, the city has grown from a small orchard community to a larger mid-sized city.
"With revitalization of the downtown core, and busy evening cabaret and restaurant district, we recommend removing the time restriction for sitting and lying on sidewalks from the old definition allowing individuals to do so in a commercial or industrial one outside of regular business hours," said Wise.
"This will help us address incidents we are having and some of the concerns in the downtown core around the restaurant and cabaret district."
Coun. Brad Sieben says the overarching issue is one that's on council's mind consistently
"This isn't council working without a heart," he says.
They also changed the definition of chattel. It now excludes soiled clothing, bedding, perishable food and personal hygiene items, among other things.
Wise says it's a change to what will, and will not, be impounded under chattel.
The length of impoundment was also changed from 60 days to 30 days for vehicles and trailers and 14 days for items of chattel.
"We have had a significant increase in the impoundment of encampments in and around back alleyways and laneways. Approximately one per cent is being reclaimed."
Several other parking and traffic bylaws were also amended or changed. |
Hey I Know This Probably Sounds Like A Stupid Question We Are Learning About Pupillary Reactions Perla How Will The Pupils React To Light If Someone Is Blind In One Eye?????
Thanks
They should still both be equal in size.
"Shining a light in one eye of a normal subject causes both pupils to constrict equally. The pupillary reaction in the illuminated eye is called the direct response, and the reaction in the other eye is the consensual response. Because of the hemidecussation of afferent pupillomotor fibers at the chiasm, and because there is another hemidecussation of the pupillomotor fibres in the brain stem, the direct and consensual pupillary responses are equal. If one eye is blind, all input to the pupillary centers in the brain stem comes from the other eye, but the double hemidecussation ensures equal pupillary innervation and there will be not anisocoria
Shining a dim light in one eye of a normal subject will cause both puils to constrict. A brighter light will cause more constriction. If, after shining a light in one eye, the light is quickly switched to the other eye, the response will be an initial constriction of both pupils followed by an equivalent re-dilation."
From "Neuro-ophthalmology. Basic and Clinical Science Course 1996-1997" American Academy of Ophthalmology.
and
"Pathophysiology: Pupil size is governed by the tone of the pupillary sphincter (parasympathetic) and the pupillary dilator muscles (sympathetic) in response to ambient light, adrenergic tone, and local pharmacologic or pathophysiologic conditions. Approximately 50% of the fibers of the optic nerve decussate in the optic chiasm, and the input to each of the parasympathetic nuclei in the brain stem remains equal. Under normal conditions, the pupils remain equal at all times in all levels of light. Therefore, anisocoria never is caused by retinal pathology. Even blindness in one eye does not cause anisocoria."
This is an area where I feel WEAK. And now realizing my co- workers don't so much. Thank you so much for the info! I had 2 neuro pts last pm and in the ER and one was a 16yr old who had been assaulted. His pupils started out equal but became unequal. My second pt was legally blind and the RN going off said "I didn't do pupil checks, he's legally blind,they don't react." I thought he knew what he was talking about since he has been an ED RN longer than me. Guess not. |
The book is bilingual and includes all the cat cafes on this blog that are still currently in business. At my favorite cafes, I’ve done interviews and included more detailed information about some of the cats. The cafes all have star ratings and are divided up by type so readers can easily find the cafe they want to go to.
This was the third pet cafe I went to in Vietnam, and it is home to more than 20 cats, mostly purebred. There are many Maine Coons, a Siamese and a few mixed breeds. This cafe has a ‘cuddle fee’ of VND45,000 and drinks are optional. 這是我去的第三間越南寵物咖啡. 他們有20幾隻貓, 大部分是品種的. 有很多緬因貓, 一隻暹羅貓, 還有一些米克斯. 咖啡館有門票費VND45,000, 不需要點飲料.
The cafe is well-lit and has plenty of open space as well as lots of places for the cats to climb, play and hide. 店裡很亮, 有很多空間還有很多地方貓可以玩.
The cats were not as friendly as at Ailu Cat House but they didn’t mind being petted. The cafe is very clean and doesn’t smell at all. It has a quiet atmosphere and quite a few people had brought computers, happy to work/study surrounded by sleeping cats. 貓咪不怕人, 但是對人沒有興趣, 只要睡覺. 有很多貓, 還是很乾淨沒有味道. 環境很安靜, 很多人用電腦, 開心有貓陪他們.
When I took a trip to Vietnam, of course I had to see if they had cat cafes. I thought it was unlikely, but to my surprise, they had a few! This cafe has three floors, with the first floor being a Japanese restaurant, the second a cat cafe and the third a dog cafe (not much to the dog cafe, just a room with three little dogs). The cat cafe has 19 adorable, friendly cats.
One cat sat on my table. They told me his name was ‘dog’ in Vietnamese because he acts like a dog. I ordered an avocado smoothie (VND 60,000) and that was very good. 一隻貓坐在我桌子上. 店員說他的名字是’狗’應為牠個性像狗. 我點一個鱷梨冰沙.
The cafe seemed very clean and there were lots of places for the cats to play. It did have a bit of a smell, but the staff were in the process of cleaning. 咖啡裡面看起來很乾淨, 有很多地方貓可以玩. 有一點貓尿味道, 但是店員一直在清理.
They had a couple of kittens that were a few months old and some very tiny ones that were still with their mother. 他們有兩個小貓, 還有一些剛出生的小貓跟他們的媽媽在一起.
This was a very nice cafe and it seems like the staff really care about the cats. Here are more pictures of the cats我很喜歡這間,好像店員很關心貓:
A friend brought me to this relatively new cat cafe in Kuala Lumpur, and it’s definitely worth a visit. It’s bright, clean and has up to 20 friendly cats at a time. All of the cats are rescue cats and some of them can be adopted. When we went in, this fluffy cat was on the counter and it stayed there the whole time 我朋友帶我去這間吉隆坡的貓咖啡, 我覺得非常好. 很亮,很乾淨, 有大概20隻貓. 全部的貓以前是流浪貓, 一些可以被領養的. 我們進去的時候這隻貓躺在櫃檯, 一直留在這裡:
The whole place is an ideal cat playground, with shelves all around the walls for the cats to jump and climb on 這個地方很適合讓貓玩得很開心, 我很多地方牠們可以跳爬上去.
Most of the seating is beanbag chairs, although there is one area with a desk built into the wall and plugs for computers/chargers. The cats like the beanbag chairs. 大部分的坐位是豆袋椅, 但是還有一個地方有插座,人可以用電腦, 充電. 貓喜歡豆袋椅.
They also have lots of artificial grass for the cats to play and sleep on. 也有很多’草’貓可以玩, 睡覺.
Entry is MYR15 for an hour and includes one drink. The drinks on the menu all have cute names. I had the Mango Meownia. 進去要MYR15,含一杯飲料. 菜單飲料的名字都很可愛. 我喝’Mango Meownia’.
This cafe has a relaxing atmosphere, and it’s nice to see how happy and comfortable all the cats look. 我很喜歡這間, 環境很好. 貓都看起來很開心, 很舒服.
I have now been to nearly every cat cafe in Taiwan, about 80 in all. Out of all of these, here are my top 10 favorites. In my opinion, the best cat cafes have happy, healthy cats (whether it’s one cat or ten), are clean, have a good atmosphere, creative design and reasonably good drinks and food.
小貓花園 (Cafe Cats and Dog) This is the original cat cafe, opened in 1998. They have about 12 cats and now 3 dogs, friendly staff and an extensive menu. 這是台灣最老的貓咖啡, 1998開業. 他們有十幾隻貓三隻狗, 友善的店員, 菜單有很多選擇.
Cat Lair 六號貓洞 (Taichung 台中) I love this cafe even though I’ve only been there twice since it’s in Taichung. There are 5-10 cats there at a time, all happy and more or less friendly. With the tree branches around the doorway, it feels like a secret hideaway in a forest even though it’s in the middle of the city. The cats are so friendly and happy, and the owner is nice to talk to and very obviously enjoys her job. It’s a great place to relax; one could easily spend a few hours here and hardly notice the passing time. 我很喜歡這間; 我只去過兩次因為在台中. 有5-10貓, 都看起來很開心. 我很喜歡這間環境, 我覺得名字很適合. 門口有很大的樹枝, 感覺像森林裡的小洞. 貓都很開心很放鬆. 還有老闆很熱情還有很明顯愛她的工作. 是一個好地方放鬆, 可以坐這裡好幾個小時.
Mask Cat 貓裝 I’ve been to this cafe more times than any others. They have three very friendly cats who will sit on people’s laps, cute decorations, and a quiet atmosphere for working. 我最常去這間咖啡. 他們有三隻很可愛的貓,會坐在人身上, 可愛的裝飾, 還有安靜的環境所以可以工作.
Collection for Friends 私藏不藏私 This cafe only has one cat, Money, but the cat is so cute and the atmosphere, decorations and food are so good, it still makes the list as one of the best. 這間只有一隻貓, Money, 但是牠很可愛, 還有環境, 裝飾, 食物都非常好所以我覺得是很好的貓咖啡.
Genki Cats 元氣貓主題餐廳 This cafe is home to about 20 beautiful Maine Coon cats. Since so many stray cats need homes, I usually prefer cafes with mixed breeds but these cats are so friendly and happy, I’ll make an exception with this one. They’ve moved since I first wrote about them. I updated the address in the original post. They also now serve full, Japanese style meals in the same room as the cats rather than shaved ice in a separate room. 者間有大概20隻很漂亮的緬因貓. 因為很多流浪貓需要一個好家, 我平常喜歡有領養流浪貓的咖啡館. 但是這些貓非常開心非常親人所以我還是很喜歡這間. 他們有搬家. 我已經改好地址在原本的post. 他們現在有日式料理, 可以吃在貓區.
Cafe Fima 菲瑪咖啡 This cafe also just has one cat, but she’s really the star of the cafe and even has her own business card. It also has a great atmosphere and high quality coffee. 這間只有一隻貓, 但是她是店裡的明星. 她有自己的名片. 氣氛很好還有咖啡特別好喝.
Spring Day Pet Cafe 春日寵物咖啡 This pet cafe has 4-6 cats and about four dogs. They have one of the most amazing cats I’ve ever seen–she can do tricks on command! 這間有4-6隻貓,四隻狗. 他們有一隻很奇妙的貓, 她會做特技跟狗一樣!
Cafe 218 小猴子咖啡 This cafe has two fluffy Persian cats that the owner adopted. It’s a small place near Taipei 101. The cats are adorable to watch, the owner is very friendly and the coffee is delicious. 這間有兩隻伯斯貓, 老闆領養的. 是一個小間在101附近. 老闆很友善, 貓很可愛, 咖啡很好喝.
品客 (Classic) This Shida cafe has three friendly cats and occasionally a Corgi. It has a convenient location, good food and nice atmosphere. 這間師大咖啡有三隻可愛的貓還有偶爾一隻柯基犬. 環境很方便, 食物好吃, 氣氛很好.
Minou Minou This Gongguan cafe has two adorable cats and very cute decorations. 弟寶,who was a kitten when I first saw him, is the friendliest, but the other cat looks sleepy and content. They have a great brunch menu. 這間公館咖啡有兩隻很可愛的貓還有很可愛的裝飾. 弟寶, 最年輕的貓比較會靠近人, 但是裡外隻野看起來很開心在睡覺. 菜單有很多好吃的早午餐.
The cats in this Taichung café are Munchkin/English shorthair mixes, and they look adorable. Some are friendly and some are a bit skittish. 這間台中咖啡的貓是萌英國短毛貓, 牠們腿很短很可愛. 一些喜歡人, 一些怕人.
Also, unfortunately some of them don’t use the litterbox. I smelled a strong odor when I went in, and while I was there, I saw one pee on the floor and no one cleaned it up. I ordered beer in a bottle (NT$150+10% service charge), since that seemed like a clean choice. They have a good variety of beers available. They also have coffee, tea and set meals. It’s nice to see the cats there, but with the smell, I didn’t have much appetite for food or drink. 還有一些不用貓砂盆. 我進去聞到很重貓尿味道. 我也看到一隻尿在地板沒有人清理. 我點一瓶啤酒(NT$150+10%服務費)因為好像最乾淨的選擇. 他們有很多種啤酒. 還有咖啡, 茶, 套餐. 貓很可愛, 但是有這個臭味, 我不想吃喝東西.
This Taichung cat café has about ten friendly cats. It’s clean and bright and the cats have lots of room to climb and play. 這間台中貓咖啡有大概十隻很親人的貓. 很乾淨又很亮, 貓有很多空間可以玩.
It’s quite busy and seems to be popular with families and groups of friends. They offer the usual coffees, teas, desserts and light meal options. I had an apple tart (NT$70) and an Americano (NT$80).
This is a nice café and I’m impressed with how clean they keep it with the number of cats. It’s not quite as unique as some of my favorites, but it’s worth a visit if you’re in the area. 客人很多, 好像家庭, 朋友團都喜歡. 他們有咖啡,茶, 甜點, 間餐. 我吃過蘋果塔(NT$70)喝美式咖啡(NT$80). 我覺得這間很好, 有很多貓還是很乾淨. 沒有特色, 但是在附近, 很值得去. |
app = require 'application'
# The function called from index.html
$ ->
require 'lib/app_helpers'
# init
###
global variables
###
# app, for nasty tricks
window.app = app
app.initialize()
|
Q:
ggplot2 annotate layer position in R
In my plot I have both legends and text annotations. For legends, I can specify
legend.justification=c(1,0), legend.position=c(1,0)
to locate the position relative to the plotting region (e.g. topright, bottomleft). However, when I put an annotate layer (http://docs.ggplot2.org/0.9.3.1/annotate.html), it seems that I can only specify the coordinates of the text
annotate("text", x = 8e-7, y = 1e-5, label=data.note, size = 5)
instead of the position of the plotting region (I want to put the text in the bottomleft corner). The length of the text (label) may vary for different plots. Is there a way to achieve this? Thanks!
A:
You can use the fact that -Inf and Inf will get mapped to the extremes of the position scales without extending them to place it in the bottom left corner. hjust and vjust are needed to make the reference point the lower left corner of your text. [using jlhoward's mock data.]
set.seed(1)
df <- data.frame(x=rnorm(100),y=rnorm(100))
ggplot(df, aes(x,y)) +geom_point()+
annotate("text",x=-Inf,y=-Inf,hjust=0,vjust=0,label="Text annotation")
A:
Is this what you're looking for??
set.seed(1)
df <- data.frame(x=rnorm(100),y=rnorm(100))
ggplot(df, aes(x,y)) +geom_point()+
annotate("text",x=min(df$x),y=min(df$y),hjust=.2,label="Text annotation")
There will probably be a bit of experimentation with hjust=... needed to get this exactly at the bottom left.
A:
The "Inf" solution has problems when you want multi-line text. In addition, it there is no margin between the text and the panel edge, which is ugly. The other solution requires explicit mention of the data which is not good either.
The desired effect can be achieved nicely with annotation_custom (or in my example, the proto Geom directly). You have configurable margin, text and box justification.
The added bonus in the following code is that you can specify which facet to annotate with something like facets=data.frame(cat1='blue', cat2='tall').
library("ggplot2")
annotate_textp <- function(label, x, y, facets=NULL, hjust=0, vjust=0, color='black', alpha=NA,
family=thm$text$family, size=thm$text$size, fontface=1, lineheight=1.0,
box_just=ifelse(c(x,y)<0.5,0,1), margin=unit(size/2, 'pt'), thm=theme_get()) {
x <- scales::squish_infinite(x)
y <- scales::squish_infinite(y)
data <- if (is.null(facets)) data.frame(x=NA) else data.frame(x=NA, facets)
tg <- grid::textGrob(
label, x=0, y=0, hjust=hjust, vjust=vjust,
gp=grid::gpar(col=alpha(color, alpha), fontsize=size, fontfamily=family, fontface=fontface, lineheight=lineheight)
)
ts <- grid::unit.c(grid::grobWidth(tg), grid::grobHeight(tg))
vp <- grid::viewport(x=x, y=y, width=ts[1], height=ts[2], just=box_just)
tg <- grid::editGrob(tg, x=ts[1]*hjust, y=ts[2]*vjust, vp=vp)
inner <- grid::grobTree(tg, vp=grid::viewport(width=unit(1, 'npc')-margin*2, height=unit(1, 'npc')-margin*2))
layer(
data = NULL,
stat = StatIdentity,
position = PositionIdentity,
geom = GeomCustomAnn,
inherit.aes = TRUE,
params = list(
grob=grid::grobTree(inner),
xmin=-Inf,
xmax=Inf,
ymin=-Inf,
ymax=Inf
)
)
}
qplot(1:10,1:10) + annotate_text2('some long text\nx = 1', x=0.5, y=0.5, hjust=1)
|
/* SPDX-License-Identifier: MIT
*
* Permission is hereby granted, free of charge, to any person
* obtaining a copy of this software and associated documentation
* files (the "Software"), to deal in the Software without
* restriction, including without limitation the rights to use, copy,
* modify, merge, publish, distribute, sublicense, and/or sell copies
* of the Software, and to permit persons to whom the Software is
* furnished to do so, subject to the following conditions:
*
* The above copyright notice and this permission notice shall be
* included in all copies or substantial portions of the Software.
*
* THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
* EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF
* MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND
* NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS
* BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN
* ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN
* CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE
* SOFTWARE.
*
* Copyright:
* 2020 Evan Nemerson <evan@nemerson.com>
* 2020 Himanshi Mathur <himanshi18037@iiitd.ac.in>
* 2020 Hidayat Khan <huk2209@gmail.com>
*/
#if !defined(SIMDE_X86_AVX512_SUB_H)
#define SIMDE_X86_AVX512_SUB_H
#include "types.h"
#include "../avx2.h"
#include "mov.h"
HEDLEY_DIAGNOSTIC_PUSH
SIMDE_DISABLE_UNWANTED_DIAGNOSTICS
SIMDE_BEGIN_DECLS_
SIMDE_FUNCTION_ATTRIBUTES
simde__m512i
simde_mm512_sub_epi8 (simde__m512i a, simde__m512i b) {
#if defined(SIMDE_X86_AVX512BW_NATIVE)
return _mm512_sub_epi8(a, b);
#else
simde__m512i_private
r_,
a_ = simde__m512i_to_private(a),
b_ = simde__m512i_to_private(b);
#if defined(SIMDE_VECTOR_SUBSCRIPT_OPS)
r_.i8 = a_.i8 - b_.i8;
#else
SIMDE_VECTORIZE
for (size_t i = 0 ; i < (sizeof(r_.m256i) / sizeof(r_.m256i[0])) ; i++) {
r_.m256i[i] = simde_mm256_sub_epi8(a_.m256i[i], b_.m256i[i]);
}
#endif
return simde__m512i_from_private(r_);
#endif
}
#if defined(SIMDE_X86_AVX512BW_ENABLE_NATIVE_ALIASES)
#undef _mm512_sub_epi8
#define _mm512_sub_epi8(a, b) simde_mm512_sub_epi8(a, b)
#endif
SIMDE_FUNCTION_ATTRIBUTES
simde__m512i
simde_mm512_mask_sub_epi8 (simde__m512i src, simde__mmask64 k, simde__m512i a, simde__m512i b) {
#if defined(SIMDE_X86_AVX512BW_NATIVE)
return _mm512_mask_sub_epi8(src, k, a, b);
#else
return simde_mm512_mask_mov_epi8(src, k, simde_mm512_sub_epi8(a, b));
#endif
}
#if defined(SIMDE_X86_AVX512BW_ENABLE_NATIVE_ALIASES)
#undef _mm512_mask_sub_epi8
#define _mm512_mask_sub_epi8(src, k, a, b) simde_mm512_mask_sub_epi8(src, k, a, b)
#endif
SIMDE_FUNCTION_ATTRIBUTES
simde__m512i
simde_mm512_maskz_sub_epi8 (simde__mmask64 k, simde__m512i a, simde__m512i b) {
#if defined(SIMDE_X86_AVX512BW_NATIVE)
return _mm512_maskz_sub_epi8(k, a, b);
#else
return simde_mm512_maskz_mov_epi8(k, simde_mm512_sub_epi8(a, b));
#endif
}
#if defined(SIMDE_X86_AVX512BW_ENABLE_NATIVE_ALIASES)
#undef _mm512_maskz_sub_epi8
#define _mm512_maskz_sub_epi8(k, a, b) simde_mm512_maskz_sub_epi8(k, a, b)
#endif
SIMDE_FUNCTION_ATTRIBUTES
simde__m512i
simde_mm512_sub_epi16 (simde__m512i a, simde__m512i b) {
#if defined(SIMDE_X86_AVX512BW_NATIVE)
return _mm512_sub_epi16(a, b);
#else
simde__m512i_private
r_,
a_ = simde__m512i_to_private(a),
b_ = simde__m512i_to_private(b);
#if defined(SIMDE_VECTOR_SUBSCRIPT_OPS)
r_.i16 = a_.i16 - b_.i16;
#else
SIMDE_VECTORIZE
for (size_t i = 0 ; i < (sizeof(r_.m256i) / sizeof(r_.m256i[0])) ; i++) {
r_.m256i[i] = simde_mm256_sub_epi16(a_.m256i[i], b_.m256i[i]);
}
#endif
return simde__m512i_from_private(r_);
#endif
}
#if defined(SIMDE_X86_AVX512BW_ENABLE_NATIVE_ALIASES)
#undef _mm512_sub_epi16
#define _mm512_sub_epi16(a, b) simde_mm512_sub_epi16(a, b)
#endif
SIMDE_FUNCTION_ATTRIBUTES
simde__m512i
simde_mm512_sub_epi32 (simde__m512i a, simde__m512i b) {
#if defined(SIMDE_X86_AVX512F_NATIVE)
return _mm512_sub_epi32(a, b);
#else
simde__m512i_private
r_,
a_ = simde__m512i_to_private(a),
b_ = simde__m512i_to_private(b);
#if defined(SIMDE_VECTOR_SUBSCRIPT_OPS)
r_.i32 = a_.i32 - b_.i32;
#else
SIMDE_VECTORIZE
for (size_t i = 0 ; i < (sizeof(r_.m256i) / sizeof(r_.m256i[0])) ; i++) {
r_.m256i[i] = simde_mm256_sub_epi32(a_.m256i[i], b_.m256i[i]);
}
#endif
return simde__m512i_from_private(r_);
#endif
}
#if defined(SIMDE_X86_AVX512F_ENABLE_NATIVE_ALIASES)
#undef _mm512_sub_epi32
#define _mm512_sub_epi32(a, b) simde_mm512_sub_epi32(a, b)
#endif
SIMDE_FUNCTION_ATTRIBUTES
simde__m512i
simde_mm512_mask_sub_epi32 (simde__m512i src, simde__mmask16 k, simde__m512i a, simde__m512i b) {
#if defined(SIMDE_X86_AVX512F_NATIVE)
return _mm512_mask_sub_epi32(src, k, a, b);
#else
return simde_mm512_mask_mov_epi32(src, k, simde_mm512_sub_epi32(a, b));
#endif
}
#if defined(SIMDE_X86_AVX512F_ENABLE_NATIVE_ALIASES)
#undef _mm512_mask_sub_epi32
#define _mm512_mask_sub_epi32(src, k, a, b) simde_mm512_mask_sub_epi32(src, k, a, b)
#endif
SIMDE_FUNCTION_ATTRIBUTES
simde__m512i
simde_mm512_maskz_sub_epi32(simde__mmask16 k, simde__m512i a, simde__m512i b) {
#if defined(SIMDE_X86_AVX512F_NATIVE)
return _mm512_maskz_sub_epi32(k, a, b);
#else
return simde_mm512_maskz_mov_epi32(k, simde_mm512_sub_epi32(a, b));
#endif
}
#if defined(SIMDE_X86_AVX512F_ENABLE_NATIVE_ALIASES)
#undef _mm512_maskz_sub_epi32
#define _mm512_maskz_sub_epi32(k, a, b) simde_mm512_maskz_sub_epi32(k, a, b)
#endif
SIMDE_FUNCTION_ATTRIBUTES
simde__m512i
simde_mm512_sub_epi64 (simde__m512i a, simde__m512i b) {
#if defined(SIMDE_X86_AVX512F_NATIVE)
return _mm512_sub_epi64(a, b);
#else
simde__m512i_private
r_,
a_ = simde__m512i_to_private(a),
b_ = simde__m512i_to_private(b);
#if defined(SIMDE_VECTOR_SUBSCRIPT_OPS)
r_.i64 = a_.i64 - b_.i64;
#else
SIMDE_VECTORIZE
for (size_t i = 0 ; i < (sizeof(r_.m256i) / sizeof(r_.m256i[0])) ; i++) {
r_.m256i[i] = simde_mm256_sub_epi64(a_.m256i[i], b_.m256i[i]);
}
#endif
return simde__m512i_from_private(r_);
#endif
}
#if defined(SIMDE_X86_AVX512F_ENABLE_NATIVE_ALIASES)
#undef _mm512_sub_epi64
#define _mm512_sub_epi64(a, b) simde_mm512_sub_epi64(a, b)
#endif
SIMDE_FUNCTION_ATTRIBUTES
simde__m512i
simde_mm512_mask_sub_epi64 (simde__m512i src, simde__mmask8 k, simde__m512i a, simde__m512i b) {
#if defined(SIMDE_X86_AVX512F_NATIVE)
return _mm512_mask_sub_epi64(src, k, a, b);
#else
return simde_mm512_mask_mov_epi64(src, k, simde_mm512_sub_epi64(a, b));
#endif
}
#if defined(SIMDE_X86_AVX512F_ENABLE_NATIVE_ALIASES)
#undef _mm512_mask_sub_epi64
#define _mm512_mask_sub_epi64(src, k, a, b) simde_mm512_mask_sub_epi64(src, k, a, b)
#endif
SIMDE_FUNCTION_ATTRIBUTES
simde__m512i
simde_mm512_maskz_sub_epi64(simde__mmask8 k, simde__m512i a, simde__m512i b) {
#if defined(SIMDE_X86_AVX512F_NATIVE)
return _mm512_maskz_sub_epi64(k, a, b);
#else
return simde_mm512_maskz_mov_epi64(k, simde_mm512_sub_epi64(a, b));
#endif
}
#if defined(SIMDE_X86_AVX512F_ENABLE_NATIVE_ALIASES)
#undef _mm512_maskz_sub_epi64
#define _mm512_maskz_sub_epi64(k, a, b) simde_mm512_maskz_sub_epi64(k, a, b)
#endif
SIMDE_FUNCTION_ATTRIBUTES
simde__m512
simde_mm512_sub_ps (simde__m512 a, simde__m512 b) {
#if defined(SIMDE_X86_AVX512F_NATIVE)
return _mm512_sub_ps(a, b);
#else
simde__m512_private
r_,
a_ = simde__m512_to_private(a),
b_ = simde__m512_to_private(b);
#if defined(SIMDE_VECTOR_SUBSCRIPT_OPS)
r_.f32 = a_.f32 - b_.f32;
#else
SIMDE_VECTORIZE
for (size_t i = 0 ; i < (sizeof(r_.m256) / sizeof(r_.m256[0])) ; i++) {
r_.m256[i] = simde_mm256_sub_ps(a_.m256[i], b_.m256[i]);
}
#endif
return simde__m512_from_private(r_);
#endif
}
#if defined(SIMDE_X86_AVX512F_ENABLE_NATIVE_ALIASES)
#undef _mm512_sub_ps
#define _mm512_sub_ps(a, b) simde_mm512_sub_ps(a, b)
#endif
SIMDE_FUNCTION_ATTRIBUTES
simde__m512
simde_mm512_mask_sub_ps (simde__m512 src, simde__mmask16 k, simde__m512 a, simde__m512 b) {
#if defined(SIMDE_X86_AVX512F_NATIVE)
return _mm512_mask_sub_ps(src, k, a, b);
#else
return simde_mm512_mask_mov_ps(src, k, simde_mm512_sub_ps(a, b));
#endif
}
#if defined(SIMDE_X86_AVX512F_ENABLE_NATIVE_ALIASES)
#undef _mm512_mask_sub_ps
#define _mm512_mask_sub_ps(src, k, a, b) simde_mm512_mask_sub_ps(src, k, a, b)
#endif
SIMDE_FUNCTION_ATTRIBUTES
simde__m512
simde_mm512_maskz_sub_ps(simde__mmask16 k, simde__m512 a, simde__m512 b) {
#if defined(SIMDE_X86_AVX512F_NATIVE)
return _mm512_maskz_sub_ps(k, a, b);
#else
return simde_mm512_maskz_mov_ps(k, simde_mm512_sub_ps(a, b));
#endif
}
#if defined(SIMDE_X86_AVX512F_ENABLE_NATIVE_ALIASES)
#undef _mm512_maskz_sub_ps
#define _mm512_maskz_sub_ps(k, a, b) simde_mm512_maskz_sub_ps(k, a, b)
#endif
SIMDE_FUNCTION_ATTRIBUTES
simde__m512d
simde_mm512_sub_pd (simde__m512d a, simde__m512d b) {
#if defined(SIMDE_X86_AVX512F_NATIVE)
return _mm512_sub_pd(a, b);
#else
simde__m512d_private
r_,
a_ = simde__m512d_to_private(a),
b_ = simde__m512d_to_private(b);
#if defined(SIMDE_VECTOR_SUBSCRIPT_OPS)
r_.f64 = a_.f64 - b_.f64;
#else
SIMDE_VECTORIZE
for (size_t i = 0 ; i < (sizeof(r_.m256d) / sizeof(r_.m256d[0])) ; i++) {
r_.m256d[i] = simde_mm256_sub_pd(a_.m256d[i], b_.m256d[i]);
}
#endif
return simde__m512d_from_private(r_);
#endif
}
#if defined(SIMDE_X86_AVX512F_ENABLE_NATIVE_ALIASES)
#undef _mm512_sub_pd
#define _mm512_sub_pd(a, b) simde_mm512_sub_pd(a, b)
#endif
SIMDE_FUNCTION_ATTRIBUTES
simde__m512d
simde_mm512_mask_sub_pd (simde__m512d src, simde__mmask8 k, simde__m512d a, simde__m512d b) {
#if defined(SIMDE_X86_AVX512F_NATIVE)
return _mm512_mask_sub_pd(src, k, a, b);
#else
return simde_mm512_mask_mov_pd(src, k, simde_mm512_sub_pd(a, b));
#endif
}
#if defined(SIMDE_X86_AVX512F_ENABLE_NATIVE_ALIASES)
#undef _mm512_mask_sub_pd
#define _mm512_mask_sub_pd(src, k, a, b) simde_mm512_mask_sub_pd(src, k, a, b)
#endif
SIMDE_FUNCTION_ATTRIBUTES
simde__m512d
simde_mm512_maskz_sub_pd(simde__mmask8 k, simde__m512d a, simde__m512d b) {
#if defined(SIMDE_X86_AVX512F_NATIVE)
return _mm512_maskz_sub_pd(k, a, b);
#else
return simde_mm512_maskz_mov_pd(k, simde_mm512_sub_pd(a, b));
#endif
}
#if defined(SIMDE_X86_AVX512F_ENABLE_NATIVE_ALIASES)
#undef _mm512_maskz_sub_pd
#define _mm512_maskz_sub_pd(k, a, b) simde_mm512_maskz_sub_pd(k, a, b)
#endif
SIMDE_END_DECLS_
HEDLEY_DIAGNOSTIC_POP
#endif /* !defined(SIMDE_X86_AVX512_SUB_H) */
|
Happy Indie Friday y'all! This week I thought I'd focus on a few scents by Wiggle Perfume and Sundries , a purveyor of delightful perfume oils. Since fragrance is a highly personal thing (what with subjectivity and different body chemistries and all) please bear in mind that what smells awesome to me may not smell awesome to you and vice-versa, but maybe this will give you a general idea of what some of these perfumes are like. Wiggle Perfume is based out of Washington state and their Etsy shop has a retro, feminine vibe (though they do have a few men's fragrances on offer). I heard about this shop when I asked around on the Indie Makeup subreddit about perfumers that do really good florals, so I picked up sample vials of a couple of their florals and some other stuff too. The samples are $3 apiece - here's a pic for size comparison:I ordered five samples and she threw in a sixth one for free - bonus. Here's what I got:I think the description of the notes in this fragrance is pretty apt, though the dominant scent to my nose is definitely tea. I also get a whiff of the "boozy little kick" straight away. The other notes sort of blend together, but they're all still there... at first it smells a bit fruity, but then I think it smells more floral, yet there's a definitely an element of spiciness behind it all. I'm not sure if this fragrance suits me personally, but it's interesting, and if the idea of a cozy tea scent that isn't straight-up tea appeals to you then this may be worth a try.I'll be honest... this blend smells like soap to me. But like the world's fanciest soap, the kind of thing you'd find in a rich old lady's bathroom. I can really smell the jasmine in this, so if that's something that doesn't normally agree with your body chemistry I'd probably skip this one. In a less concrete sense, this smells sort of like a summer breeze on humid night to me, but like... in soap form. I honestly can't decide if I like it or not... it doesn't smell bad, but I don't think I'd want to smell it on my body all day. In a diffuser or something it would probably be awesome though, because it's fresh and summery and sort of elegant.This is EXACTLY the type of fragrance I was looking for when I first heard of Wiggle Perfume. Buxom is an old-fashioned (but very grand) floral fragrance with a sweet, vanilla-y edge. I smell a bit of a boozy note in the bottle, but it seems to dissipate once applied to my skin. This one is definitely on the strong side, and not for those who find rose scents distasteful or old-ladyish. I find this to be a bit more playful than some rose fragrances, but rose is unquestionably still the dominant note. A sexy scent with a bit of innocent sweetness behind it. Would purchase in full size.Anjali also has a bit of a soapy quality to me, but not as much as Selene. I'm thinking it might be the jasmine since it's in both of them? Anyway, I definitely smell the coconut and amber in there, with just a hint of jasmine... I can't quite pick up on the clove and carnation, but maybe they're just in there for support. Despite the slight soapiness on me I really like this fragrance. It's unusual but inviting. I may purchase this in full size... not 100% sure yet.This was the freebie vial. I probably wouldn't have chosen this myself, but it's actually quite good. The dominant note is tea, but there's a prominent citrus element straight out of the bottle. As it dries down the floral and spicy notes become more noticeable. This wasn't quite what I was looking for but it suits me surprisingly well, and generally speaking it just smells really cheerful and good. When my boyfriend came home from work yesterday he said "Ooh, it smells so good! Are you burning a scented candle?" Nope, just the perfume.Another really fabulous, old-fashioned floral. If you like Buxom I think there's a good chance you'd also like this one, though Lila feels like Buxom's darker, sultrier older sister. I came to Wiggle Perfume looking for something like Buxom, but I think I might like this one even better. Would purchase in full size.This is sort of amazing, but I liked every single fragrance I sampled from Wiggle. The only one I'm certain I wouldn't buy for myself is Odessa, but not because I thought it smelled bad on me, rather because it's a bit more subtle on me than the others and I love to reek like the inside of a candle shop. I'm 100% sold on Buxom and Lila, and considering the others (especially Anjali) in full size. Plus there are a number of other scents in their catalog I want to try...Most of these scents have a romantic, retro feel and a bit of a sexy vibe. I think they're sort of old-fashioned (in a good way), but if you're usually averse to really bold fragrances or "old lady" scents I would definitely order samples first.In terms of the particularities of ordering from Wiggle, it was uneventful. I think the turnaround time from order to shipment was about 10 days, which isn't especially long compared to other indie sellers. Everything was packed securely in a bubble mailer, no errors, no leaking, no problems. I will order again. Or I will make someone else order for me as a birthday gift. :)You can find Wiggle Perfume and Sundries on Etsy . They do ship outside of the United States, though the international shipping rates are a fair bit more expensive. |
With the BattleTech: Clan Invasion Kickstarter less than two weeks away, we wanted to clear the decks and provide updates on a few recently-released and upcoming products.
Here’s what’s new for BattleTech:
–The reprint of TechManual boasting the 35th anniversary vintage cover is now available in print, PDF, and combo formats on the Catalyst Game Labs store.
—Alpha Strike: Commander’s Edition has a street date of Wednesday, July 10, 2019 and will be available from the Catalyst Game Labs store and through traditional distribution at that time.
–The BattleTech: A Game of Armored Combat boxed set is back in stock in the Catalyst Game Labs store, and will be making its way back into distribution to retailers as before.
–Another reprint of the BattleTech Beginner Box is making its way to our U.S. fulfillment center. A full restock is expected by mid- to late-August.
–Thanks to the brisk sales and enthusiasm for the recent series of BattleMats, we’re pleased to announce that a full re-order of all four previously-released mats has been placed. They will be available in the Catalyst Game Labs store and in retail stores by October. |
Floreana island is located in the far southern portion of the archipelago. The island has a total area of approximately 67 square miles, and its highest point, at 2100 feet, is a now-extinct volcano. Floreana has been inhabited the longest of any of the Galapagos islands, having been used as a water and food source by whalers and pirates as far back as the 1600's. As a result of human disturbance the wildlife of the island has been vastly disrupted, with the native giant tortoise now completely extinct and introduced rats, pigs and goats having decimated the native plants and birds.
The human history of the islands includes caves and shelters used by early buccaneers, as well as the first official settler of the Galapagos, an Irishman named Patrick Watkins who was stranded in 1803 and then settled to sell supplies to whalers. Later residents included convicts, pirates and colonists, and as recently as the 1930's there have been intrigues involving love, hate, and even mysterious deaths, as chronicled in the book A Galapagos Affair.
The town of Puerto Velasco Ibarra on the northwest side of the island offers lodging and food to visitors wanting to stay on the island.
Noted for the volcanic green olivene crystals found in the beach, Punta Cormorant offers a trail overlooking a saltwater lagoon that is a favorite of flamingos. While it is never guaranteed that flamingos will be present, this site is one of the best in the islands for spotting the colorful birds. Beyond the lagoon the trail leads to a magnificent white-sand beach, with sands so fine that the beach is sometimes referred to by guides as "flour beach". Green sea turtles lay their eggs in the sands here during the night, and their tracks leading to and from the sea mark the beach.
Post Office Bay is located along a white sand beach. Long used by whalers, the post office barrel has been in use since 1793. Today primarily tourists use the post office barrel, leaving a handful of postcards and in turn collecting postcards left by others. Traditionally it is expected that people will take only those mailings destined for people that they can personally deliver to, but these days people often settle for someone from their own country, and simply add postage and drop things in the mail upon their return home.
Today's travelers who collect post cards only to mail them to the addressees don't do anyone any favors. They completely ignore the more than 200 year old established tradition of hand delivering the cards and letters. Tour guides, as ours did, should remind the tourists to follow by this traditions. There is absolutely no pleasure is receiving a post card in California mailed from Connecticut.
A road leads from Puerto Velasco Ibarra to the highlands of Floreana. Trails to the tops of some of the hills provide excellent views of the island and, for snail lovers, provide access to one of the only endemic snails on the islands. For non-snail lovers, caves and tunnels used by buccaneers in the 17th and 18th century offer a glimpse into the human history of the islands. While it is possible to walk to some of the highland sites, most groups will travel on benches set in the backs of trucks that can be hired from town.
Arguably the best snorkeling site in the islands, Devil's Crown is a collapsed volcanic cone that boasts an extraordinary number and variety of fishes. In addition, sharks, sea lions, sea turtles and eels can be found amongst the rocks and corals. The current around Devil's Crown can be very strong, so those without strong swimming abilities should be careful.
A small island located very near Floreana, snorkeling around Champion can be excellent. Landings are not permitted on the island, but the extremely rare Charles mockingbird can sometimes be seen from the water.
The Wittmer family hotel has a shop selling souvenirs, suntan lotion, aloe, and other sundries needed by visitors. Bring cash, and be prepared to pay a premium (although not an unreasonable one) for all items. |
Q:
NSNetServiceBrowser did NOT find published service
On an iPhone (the server), I've tried to publish a service and my code ran into the NSNetService object's delegate method:
-(void)netServiceDidPublish:(NSNetService *)sender
So I believe that my service @"_chatty._tcp." has published successfully. Then on another iPhone (the client), I use NSNetServiceBrowser to find my service, but it did NOT run into the delegate method:
-(void)netServiceBrowser:(NSNetServiceBrowser *)netServiceBrowser didFindService:(NSNetService *)netService moreComing:(BOOL)moreServicesComing
I found some questions related to my case on this site, most of the answer remind to check the delegate object whether is out of scope or not. I'm sure my delegate work well because it ran into another delegate method like:
-(void)netServiceBrowserWillSearch:(NSNetServiceBrowser *)aNetServiceBrowser
Can anybody help me find out the reason?
Here are some parts of my code:
I init the service like that:
#define MY_PROTOCOL @"_chatty._tcp."
self.myService = [[NSNetService alloc]
initWithDomain:@"" type:MY_PROTOCOL
name:@"thaith" port:self.port];
The port is initialized with a given listeningSocket in the Browser class:
NSNetServiceBrowser* finder = [[NSNetServiceBrowser alloc] init];
//I also retain the finder.
finder.delegate = self;
[finder searchForServicesOfType:MY_PROTOCOL inDomain:@""];
A:
After having come across the same problem and giving up for a month. I've just come back to it and solved it:
Even though the sample code in the docs seems to imply otherwise, don't use a local variable for the NSNetServiceBrowser. As soon as it goes out of scope it gets garbage collected. Make finder an instance variable or property so its sticks around. I didn't spot this straight away as the netServiceBrowserWillSearch: delegate was getting called so I assumed everything was ok...
|
1. Field of the Invention
The present invention relates to a focal point detection device for use in a projection aligner for semiconductor manufacturing, for transferring a circuit pattern onto a wafer.
2. Description of the Related Art
There are several known surface position detection devices for use in a projection aligner. For example, Japanese Unexamined Patent Publication No. 62-299716 (U.S. Pat. No. 4,748,333) discloses one height detection system that measures the center of an exposure area on a wafer. In another device disclosed in Japanese Unexamined Patent Publication No. 2-102518 filed by the applicant of the present invention, a plurality of height detection systems are provided on an exposure area on a wafer and based on a plurality pieces of height information, the inclination and height of the exposure area are calculated and adjusted.
As seen from these known systems, most of the present surface position detection devices employ a laser, an LED or the like as a light source.
Generally speaking, in an optical system, an image of a slit illuminated by a light source is obliquely directed to a wafer to be detected using a projection imaging optical system, the slit image reflected off the wafer is re-focused on a position detection element using a image receiving optical system, and the up and down movement of the wafer to be detected is measured in the form of motion of the slit image on the position detection element.
In the optical system, resist should be applied to the surface of the wafer to be detected to the extent that the wafer is flat enough to be considered as a mirror wafer. By setting the incident angle of incident light to be 70 degrees or greater, the reflectance at the flattened resist surface of the wafer is increased to measure the resist surface position of the wafer.
A wafer has a stepwise or uneven profile with a diversity of patterns thereon.
In an integrated circuit portion in a large scale integrated circuit (LSI) chip where fine patterns are formed, the applied resist fills and smoothes the unevenness of the patterns to the extent that the resist surface is made flat enough to be considered as an optical mirror surface.
However, a large step is formed in the vicinity of a scribe line between LSI chips, and the application of resist is still unable to sufficiently fill the notch of the step.
The surface of the applied resist in the vicinity of the scribe line thus suffers dents (or projections).
The resist surface of the wafer thus has both areas considered as an optical mirror surface and other areas having an uneven profile.
As already described, when a slit image is directed to a flat resist surface considered as a mirror surface, an incident light ray is reflected at a substantially constant angle of reflection, and an image receiving optical system finely re-focuses the slit image on a position detection element.
In contrast, when the slit image is directed to the uneven resist surface, the light ray is reflected in a direction different from that reflected from the flat resist surface, and becomes a deflected light ray.
When the reflected light ray is deflected to the image receive optical system, the reflected light ray flux is fully or partially shaded, presenting difficulty in focusing the slit image on the position detection element.
Specifically, the symmetry of the re-focused slit image is destroyed, or the slit image is entirely missing. As a result, detection or measurement accuracy may be degraded, or measurement itself may become impossible.
To cope with this problem, known surface position detection devices use an oversize projected slit image to decrease the ratio of the unevenness profile area to the flat area within the reflected slit image coverage over the wafer surface or use an elongated rectangular slit image that is projected at an orientation of 45 degrees relative to the LSI chips on the wafer so that the scribe line area having an unevenness profile is relatively small with respect to the entire area of the slit image. Thus, the degree of shading through the image receiving optical system is reduced.
However, the design of LSI circuitry changes the ratio of the unevenness profile area to the entire resist surface. Thus, there is a possibility that, depending on the process used to design the LSI circuitry, the above methods are still subject to detection accuracy degradation leading to detection failure. |
Dalla Valle
Dalla Valle, your building site partner.
As a general contractor specialising in joinery work, for many years Dalla Valle has been meeting the needs of its customers in terms of physical security, more specifically the protection of property and people.
The company is located on the Péruwelz industrial estate (between Mons and Tournai), where it has fully equipped workshops for the production of joinery elements in aluminium and wood.
Operating mainly in Wallonia and Brussels, Dalla Valle undertakes the following activities on building sites:
Dalla Valle offers its know-how mainly in the sectors of public buildings, Belgian and European authorities, supermarkets and banks, as well as for private individuals and members of the liberal professions.
The company also has class 5 approval and ISIB certification for the installation of fire-resistant doors (Benor/ATG).
Backed up by years of experience, Dalla Valle will be your partner from the design to the final completion of the security systems in your buildings. |
;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;
; Copyright(c) 2011-2016 Intel Corporation All rights reserved.
;
; Redistribution and use in source and binary forms, with or without
; modification, are permitted provided that the following conditions
; are met:
; * Redistributions of source code must retain the above copyright
; notice, this list of conditions and the following disclaimer.
; * Redistributions in binary form must reproduce the above copyright
; notice, this list of conditions and the following disclaimer in
; the documentation and/or other materials provided with the
; distribution.
; * Neither the name of Intel Corporation nor the names of its
; contributors may be used to endorse or promote products derived
; from this software without specific prior written permission.
;
; THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS
; "AS IS" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT
; LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR
; A PARTICULAR PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT
; OWNER OR CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL,
; SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT
; LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE,
; DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY
; THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT
; (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE
; OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;
%include "sha1_job.asm"
%include "sha1_mb_mgr_datastruct.asm"
%include "reg_sizes.asm"
extern sha1_mb_x4_sse
extern sha1_opt_x1
default rel
%ifidn __OUTPUT_FORMAT__, elf64
; LINUX register definitions
%define arg1 rdi ; rcx
%define arg2 rsi ; rdx
; idx needs to be other than ARG1, ARG2, rax, r8-r11
%define idx rdx ; rsi
%else
; WINDOWS register definitions
%define arg1 rcx
%define arg2 rdx
; idx needs to be other than ARG1, ARG2, rax, r8-r11
%define idx rsi
%endif
; Common definitions
%define state arg1
%define job arg2
%define len2 arg2
%define unused_lanes rbx
%define lane_data rbx
%define tmp2 rbx
%define job_rax rax
%define tmp1 rax
%define size_offset rax
%define tmp rax
%define start_offset rax
%define tmp3 arg1
%define extra_blocks arg2
%define p arg2
%define tmp4 r8
%define lens0 r8
%define lens1 r9
%define lens2 r10
%define lens3 r11
; STACK_SPACE needs to be an odd multiple of 8
_XMM_SAVE_SIZE equ 10*16
_GPR_SAVE_SIZE equ 8*2
_ALIGN_SIZE equ 8
_XMM_SAVE equ 0
_GPR_SAVE equ _XMM_SAVE + _XMM_SAVE_SIZE
STACK_SPACE equ _GPR_SAVE + _GPR_SAVE_SIZE + _ALIGN_SIZE
%define APPEND(a,b) a %+ b
; SHA1_JOB* sha1_mb_mgr_flush_sse(SHA1_MB_JOB_MGR *state)
; arg 1 : rcx : state
global sha1_mb_mgr_flush_sse:function
sha1_mb_mgr_flush_sse:
sub rsp, STACK_SPACE
mov [rsp + _GPR_SAVE + 8*0], rbx
%ifidn __OUTPUT_FORMAT__, win64
mov [rsp + _GPR_SAVE + 8*1], rsi
movdqa [rsp + _XMM_SAVE + 16*0], xmm6
movdqa [rsp + _XMM_SAVE + 16*1], xmm7
movdqa [rsp + _XMM_SAVE + 16*2], xmm8
movdqa [rsp + _XMM_SAVE + 16*3], xmm9
movdqa [rsp + _XMM_SAVE + 16*4], xmm10
movdqa [rsp + _XMM_SAVE + 16*5], xmm11
movdqa [rsp + _XMM_SAVE + 16*6], xmm12
movdqa [rsp + _XMM_SAVE + 16*7], xmm13
movdqa [rsp + _XMM_SAVE + 16*8], xmm14
movdqa [rsp + _XMM_SAVE + 16*9], xmm15
%endif
; use num_lanes_inuse to judge all lanes are empty
cmp dword [state + _num_lanes_inuse], 0
jz return_null
; find a lane with a non-null job
xor idx, idx
cmp qword [state + _ldata + 1 * _LANE_DATA_size + _job_in_lane], 0
cmovne idx, [one]
cmp qword [state + _ldata + 2 * _LANE_DATA_size + _job_in_lane], 0
cmovne idx, [two]
cmp qword [state + _ldata + 3 * _LANE_DATA_size + _job_in_lane], 0
cmovne idx, [three]
; copy idx to empty lanes
copy_lane_data:
mov tmp, [state + _args + _data_ptr + 8*idx]
%assign I 0
%rep 4
cmp qword [state + _ldata + I * _LANE_DATA_size + _job_in_lane], 0
jne APPEND(skip_,I)
mov [state + _args + _data_ptr + 8*I], tmp
mov dword [state + _lens + 4*I], 0xFFFFFFFF
APPEND(skip_,I):
%assign I (I+1)
%endrep
; Find min length
mov DWORD(lens0), [state + _lens + 0*4]
mov idx, lens0
mov DWORD(lens1), [state + _lens + 1*4]
cmp lens1, idx
cmovb idx, lens1
mov DWORD(lens2), [state + _lens + 2*4]
cmp lens2, idx
cmovb idx, lens2
mov DWORD(lens3), [state + _lens + 3*4]
cmp lens3, idx
cmovb idx, lens3
mov len2, idx
and idx, 0xF
and len2, ~0xF
jz len_is_0
; compare with sha-sb threshold, if num_lanes_inuse <= threshold, using sb func
cmp dword [state + _num_lanes_inuse], SHA1_SB_THRESHOLD_SSE
ja mb_processing
; lensN-len2=idx
shr len2, 4
mov [state + _lens + idx*4], DWORD(idx)
mov r10, idx
or r10, 0x1000 ; sse has 4 lanes *4, r10b is idx, r10b2 is 16
; "state" and "args" are the same address, arg1
; len is arg2, idx and nlane in r10
call sha1_opt_x1
; state and idx are intact
jmp len_is_0
mb_processing:
sub lens0, len2
sub lens1, len2
sub lens2, len2
sub lens3, len2
shr len2, 4
mov [state + _lens + 0*4], DWORD(lens0)
mov [state + _lens + 1*4], DWORD(lens1)
mov [state + _lens + 2*4], DWORD(lens2)
mov [state + _lens + 3*4], DWORD(lens3)
; "state" and "args" are the same address, arg1
; len is arg2
call sha1_mb_x4_sse
; state and idx are intact
len_is_0:
; process completed job "idx"
imul lane_data, idx, _LANE_DATA_size
lea lane_data, [state + _ldata + lane_data]
mov job_rax, [lane_data + _job_in_lane]
mov qword [lane_data + _job_in_lane], 0
mov dword [job_rax + _status], STS_COMPLETED
mov unused_lanes, [state + _unused_lanes]
shl unused_lanes, 4
or unused_lanes, idx
mov [state + _unused_lanes], unused_lanes
sub dword [state + _num_lanes_inuse], 1
movd xmm0, [state + _args_digest + 4*idx + 0*16]
pinsrd xmm0, [state + _args_digest + 4*idx + 1*16], 1
pinsrd xmm0, [state + _args_digest + 4*idx + 2*16], 2
pinsrd xmm0, [state + _args_digest + 4*idx + 3*16], 3
mov DWORD(tmp2), [state + _args_digest + 4*idx + 4*16]
movdqa [job_rax + _result_digest + 0*16], xmm0
mov [job_rax + _result_digest + 1*16], DWORD(tmp2)
return:
%ifidn __OUTPUT_FORMAT__, win64
movdqa xmm6, [rsp + _XMM_SAVE + 16*0]
movdqa xmm7, [rsp + _XMM_SAVE + 16*1]
movdqa xmm8, [rsp + _XMM_SAVE + 16*2]
movdqa xmm9, [rsp + _XMM_SAVE + 16*3]
movdqa xmm10, [rsp + _XMM_SAVE + 16*4]
movdqa xmm11, [rsp + _XMM_SAVE + 16*5]
movdqa xmm12, [rsp + _XMM_SAVE + 16*6]
movdqa xmm13, [rsp + _XMM_SAVE + 16*7]
movdqa xmm14, [rsp + _XMM_SAVE + 16*8]
movdqa xmm15, [rsp + _XMM_SAVE + 16*9]
mov rsi, [rsp + _GPR_SAVE + 8*1]
%endif
mov rbx, [rsp + _GPR_SAVE + 8*0]
add rsp, STACK_SPACE
ret
return_null:
xor job_rax, job_rax
jmp return
section .data align=16
align 16
one: dq 1
two: dq 2
three: dq 3
|
Fantasy Football Today
Lions' Dwayne Washington: Inactive Week 13
by
RotoWire Staff
Dec 3, 2017
• 1 min read
UpdateDec 3, 2017, 4:48pm
Washington (coach's decision) is inactive for Sunday's game at Baltimore, Kyle Meinke of MLive.com reports.
Washington missed the last two games due to a hip injury, but his ability to practice in full this week forecast a return to action Week 13, especially with Ameer Abdullah inactive due to a neck concern. Instead, the Lions will rely on Theo Riddick to lead the backfield at the outset of the contest, with Zach Zenner and Tion Green available for reserve duty. |
You'd think that penguins would love the meaty taste of fish, but it turns out that they may not be able to taste their food much at all. A new genetic study out of the University of Michigan finds that penguins appear to have long ago lost the ability to taste sweet and bitter flavors, as well as the savory, meaty flavor known as umami. Together, sweet, bitter, and umami make up three of the five basic tastes. The other two, sour and salty, may still be present in penguins. The findings are being published today in Current Biology.
The fish may have been too cold for penguins to taste
So what led to penguins' believed loss of these tastes? "This is the most difficult question, especially because penguins eat fish and fish have the umami taste, so you would have predicted that the umami taste would have been useful to penguins," George Zhang, the paper's corresponding author, tells The Verge. Zhang's hypothesis — and he notes "it is still a hypothesis" — is that it's too cold down in Antarctica for these taste receptors to matter.
Prior research has shown that the tongue's receptor channels, which are what react to tastes, function poorly at lower temperatures when it comes to detecting sweet, bitter, and umami. The Michigan researchers speculate that the environment may have been so cold that this receptor was "effectively non-functional" in penguins' ancestors. "Those three tastes … would not be useful any more because the channel is not functioning," Zhang says. "So gradually mutations would accumulate in those genes and eventually they would become lost."
The study is based entirely on genetic findings, so another group of researchers will have to actually run tests with penguins to confirm that they can't taste these foods. But the study's authors are quite confident that future work will show penguins can't taste sweet, bitter, and umami flavors based on the genetic findings. "It's very clear," Zhang says. If the genes aren't there, he says, then the animals don't have those tastes.
The genes for tasting sweet, bitter, and umami were broken or missing
"The neighboring genes were all there, it's just that those specific taste genes were missing," Zhang says. "So we know it's not because the quality of the genome sequence." Zhang's research group was able to locate the genes for tasting bitter and umami flavors in around 20 other birds, but in the five penguin genomes that they looked at, including those from Adélie and emperor penguins, the genes were either broken or missing. Birds as a group are known to have lost their ability to detect sweet tastes, so that gene was absent in every sample that was tested.
The absence of bitter and umami tasting genes in the five penguins leads the researches to believe that penguins as a group likely lost this taste in their common ancestor, while the ability to detect sweet tastes appears to have been lost much farther back. Because penguins seem to have originated in the Antarctic, the researchers believe that penguins that live elsewhere should also be unable to detect these tastes, too.
(Anton_Ivanov / Shutterstock)
Though the researchers believe that penguins should still be able to detect sour and salty tastes, David Yarmolinsky, a taste researcher at Columbia who was not involved with the study, says that's still up in the air. "Really this paper can only make a statement about those three taste qualities," he says. That's because while the absence of a gene typically says something, its presence doesn't always mean the same thing.
"They did find a channel that's necessary for salt taste … but that doesn't mean a whole lot because that channel is required for your kidneys to work," he says. "If they didn't have that, they'd be dead penguins whether or not they can taste. So just because they have it in their genome doesn't mean they have it on their tongue." Yarmolinsky also says that the gene associated with the ability to detect sour tastes has complications that prevent that tasting ability from being a certainty, too.
"You really have to take the penguin and see how it reacts."
"You really have to take the penguin and see how it reacts when you give it something sour to eat," he says. "That's really the test to see what they can or cannot taste."
Earlier research suggests that what taste buds penguins do have are fairly limited, if they have them at all. That makes sense, since the main function of penguins' tongues appears to be allowing them to capture prey; penguins also swallow their food whole. "Given the way their mouths are oriented, and how they hunt, capture, and consume their prey, it’s not surprising that penguins may have limited taste perception," Michael Polito, an ecologist with Louisiana State University who was not involved with the study, writes in an email to The Verge. "Other senses, especially vision and possibly even smell, may be more important when it comes to how penguins find and identify their favorite foods in the ocean."
Whales and dolphins are also believed to have lost most of their taste, with only the salt channel remaining. Yarmolinsky notes that researchers have been looking at taste loss and its consequences in other animals lately. This study, he says, "really fits into the story that's coming out the last few years that sensor receptors are adaptive to the lifestyles of animal diet." It's also believed that taste receptors may play other roles inside the body, so a penguin's inability to detect sweet, bitter, and umami flavors could have deeper implications than just what's on its tongue. |
Introduction
============
Noninvasive ventilation (NIV) has been developed to reduce complications associated with tracheal intubation and conventional mechanical ventilation. The aim of NIV is to gain control of acute respiratory failure, avoiding intubation; however, when intubation is required, its application should not be delayed, as this may result in a worse prognosis. This is the main reason to look for reliable failure signs of the technique.
Objective
=========
To identify failure prognostic signs of NIV in pediatric acute respiratory failure.
Methods
=======
This retrospective study was based on data collection from medical records of patients admitted to the pediatric ICU of University Hospital, University of São Paulo, from March to September 2012 and during the same period in 2013. Patients were divided into two groups: success group, in which patients who used NIV did not require intubation; and failure group, which included all patients who required intubation. The following variables were analyzed: age, sex, weight, personal history, previous use of oxygen, NIV success or failure, cause of failure, respiratory rate, heart rate, oxygen saturation, PRISM, PIM, the NIV devices and ventilatory parameters during NIV placement and during withdrawal.
Results
=======
The charts of 112 patients were analyzed, 55 in the success group and 57 in the failure group. Most children who failed (32.14 %) were male. The median PRISM value in the failure group was 7 (5-8) (*p*= 0.000) and the median time of NIV use in this group was 570 (182-1230) minutes (*p*= 0.000). In the univariate analysis, PEEP (*p*= 0.003), fraction of inspired oxygen (*p*= 0.000), oxygen saturation (*p*= 0.014), respiratory rate (*p*= 0.000), heart rate (*p*= 0.000) and need for sedation (*p*= 0.000) had a statistically significant difference in the moment of NIV withdrawal in the failure group. Logistic regression analysis showed that the independent factors significantly related to NIV failure were PRISM, total time in minutes and respiratory rate at the moment of withdrawal, considering the statistically significant value of *p*\<0.05.
Conclusion
==========
The PRISM value, NIV duration and respiratory rate can predict NIV failure in the pediatric population.
|
The presently disclosed embodiments relate generally to layers that are useful in imaging apparatus members and components, for use in electrostatographic, including digital, apparatuses. More particularly, the embodiments pertain to an improved electrostatographic imaging member having a specific overcoat formulation that provides excellent mechanical properties while reducing the amount of formaldehyde released or generated and processes for making the same. In embodiments, the photoreceptor comprises an overcoat having a formaldehyde scavenger therein. In embodiments, the formaldehyde scavenger is selected from the group consisting of ethylene urea, dimethylol ethylene urea and mixtures thereof.
Electrophotographic imaging members, e.g., photoreceptors, photoconductors, imaging members, and the like, typically include a photoconductive layer formed on an electrically conductive substrate. The photoconductive layer is an insulator in the substantial absence of light so that electric charges are retained on its surface. Upon exposure to light, charge is generated by the photoactive pigment, and under applied field charge moves through the photoreceptor and the charge is dissipated.
In electrophotography, also known as xerography, electrophotographic imaging or electrostatographic imaging, the surface of an electrophotographic plate, drum, belt or the like (imaging member or photoreceptor) containing a photoconductive insulating layer on a conductive layer is first uniformly electrostatically charged. The imaging member is then exposed to a pattern of activating electromagnetic radiation, such as light. Charge generated by the photoactive pigment move under the force of the applied field. The movement of the charge through the photoreceptor selectively dissipates the charge on the illuminated areas of the photoconductive insulating layer while leaving behind an electrostatic latent image. This electrostatic latent image may then be developed to form a visible image by depositing oppositely charged particles on the surface of the photoconductive insulating layer. The resulting visible image may then be transferred from the imaging member directly or indirectly (such as by a transfer or other member) to a print substrate, such as transparency or paper. The imaging process may be repeated many times with reusable imaging members.
An electrophotographic imaging member may be provided in a number of forms. For example, the imaging member may be a homogeneous layer of a single material such as vitreous selenium or it may be a composite layer containing a photoconductor and another material. In addition, the imaging member may be layered. These layers can be in any order, and sometimes can be combined in a single or mixed layer.
Typical multilayered photoreceptors or imaging members have at least two layers, and may include a substrate, a conductive layer, an optional charge blocking layer, an optional adhesive layer, a photogenerating layer (sometimes referred to as a “charge generation layer,” “charge generating layer,” or “charge generator layer”), a charge transport layer, an optional overcoating layer and, in some belt embodiments, an anticurl backing layer. In the multilayer configuration, the active layers of the photoreceptor are the charge generation layer (CGL) and the charge transport layer (CTL). Enhancement of charge transport across these layers provides better photoreceptor performance.
The term “photoreceptor” or “photoconductor” is generally used interchangeably with the terms “imaging member.” The term “electrostatographic” includes “electrophotographic” and “xerographic.” The terms “charge transport molecule” are generally used interchangeably with the terms “hole transport molecule.”
One type of composite photoconductive layer used in xerography is illustrated in U.S. Pat. No. 4,265,990, which describes a photosensitive member having at least two electrically operative layers. One layer comprises a photoconductive layer which is capable of photogenerating holes and injecting the photogenerated holes into a contiguous charge transport layer (CTL). Generally, where the two electrically operative layers are supported on a conductive layer, the photoconductive layer is sandwiched between a contiguous CTL and the supporting conductive layer. Alternatively, the CTL may be sandwiched between the supporting electrode and a photoconductive layer. Photosensitive members having at least two electrically operative layers, as disclosed above, provide excellent electrostatic latent images when charged in the dark with a uniform negative electrostatic charge, exposed to a light image and thereafter developed with finely divided electroscopic marking particles. The resulting toner image is usually transferred to a suitable receiving member such as paper or to an intermediate transfer member which thereafter transfers the image to a member such as paper.
In the case where the charge-generating layer (CGL) is sandwiched between the CTL and the electrically conducting layer, the outer surface of the CTL is charged negatively and the conductive layer is charged positively. The CGL then should be capable of generating electron hole pair when exposed image wise and inject only the holes through the CTL. In the alternate case when the CTL is sandwiched between the CGL and the conductive layer, the outer surface of CGL layer is charged positively while conductive layer is charged negatively and the holes are injected through from the CGL to the CTL. The CTL should be able to transport the holes with as little trapping of charge as possible. In flexible web like photoreceptor the charge conductive layer may be a thin coating of metal on a thin layer of thermoplastic resin.
In a typical machine design, a drum photoreceptor is coated with one or more coatings applied by well known techniques such as dip coating or spray coating. Dip coating of drums usually involves immersing of a cylindrical drum while the axis of the drum is maintained in a vertical alignment during the entire coating and subsequent drying operation. Because of the vertical alignment of the drum axis during the coating operation, the applied coatings tend to be thicker at the lower end of the drum relative to the upper end of the drum due to the influence of gravity on the flow of the coating material. Coatings applied by spray coating can also be uneven, e.g., orange peel effect. Coatings that have an uneven thickness do not have uniform electrical properties at different locations of the coating. Under a normal machine imaging function condition, the photoreceptor is subjected to physical/mechanical/electrical/chemical species actions against the layers due to machine subsystems interactions. These machine subsystems interactions contribute to surface contamination, scratching, abrasion and rapid surface wear problems.
As electrophotography advances, the complex, highly sophisticated duplicating systems need to operate at very high speeds which places stringent requirements on imaging members and may reduce imaging member longevity. Thus, there is a continued need for achieving increased life span of photoconductive imaging members while maintaining good mechanical properties. In addition, although present photoreceptors provide excellent mechanical properties such as abrasion resistance, crack resistance and wear resistance, known crosslinking agents contain and/or generate formaldehyde in small quantities. Small quantities of formaldehyde are objectionable in the manufacturing plant due to the necessity of protective gear to avoid exposure, for example, exposure limits are less than 0.5 ppm. If transferred/coated in the open atmosphere of the pilot plant, levels can approach 20 ppm. The addition equipment to protect the plant personnel can be expensive. Therefore, it is desired to provide a photoreceptor that reduces and minimizes formaldehyde exposure. |
Subendocardial hemorrhages in a case of extrapercardial cardiac tamponade – A possible mechanism of appearance.
Subendocardial hemorrhages are grossly visible bleedings in the inner surface of the left ventricle, the interventricular septum, and the opposing papillary muscles and adjacent columnae carneae of the free wall of the ventricle. These are commonly seen in sudden profound hypotension either from severe blood loss from “shock” in the widest sense and, even more often, in combination with brain injuries. We present a case of a 38-year-old man, injured as a car driver in a frontal collision, who died c. 45 minutes after the accident. The autopsy revealed severe chest trauma, including multiple right-sided direct rib fractures with the torn parietal pleura and right-sided pneumothorax, several right lung ruptures, and a rupture of one of the lobar bronchi with pneumomediastinum, and prominent subcutaneous emphysema of the trunk, shoulders, neck and face. The patchy subendocardial hemorrhage of the left ventricle was observed. The cause of death is attributed to severe blunt force chest trauma. We postulate pneumomediastinum leading to extrapericardial tamponade as the underlying mechanism of this subendocardial hemorrhage. |
The invention relates to an anchoring rod used for anchoring an article on a base by drilling a hole in the base, inserting a compounded mass including a synthetic resin and the anchoring rod into the drilled hole.
This type of anchoring rod is known and has a head at a front end inserted in the drilled hole and a threaded portion on a rear end protruding from the hole for fixing the article to the rear end of the anchored anchoring rod.
To anchor an anchoring rod using a compounded mass, first a drilled blind hole is made in the base, the diameter of the hole being somewhat larger than the outer diameter of the anchoring rod. A glass capsule that contains the compounded mass including a synthetic resin, a hardener and additives is then inserted into the drilled hole. The capsule is crushed by insertion of the anchoring rod clamped in a drilling machine and the components of the compounded mass are activated by mixing. Once the compounded mass has hardened, the anchoring rod is firmly bonded and anchored in the drilled hole. The anchoring is based essentially on the adhesive bond between the compounded mass and the wall of the drilled hole. This bond is considerably weakened, however, when a crack runs through the location of the anchor. The compounded mass becomes detached at the wall of the drilled hole because of the drilled hole enlarging as a consequence of the crack so that only negligible holding forces remain.
Therefore DE-OS 35 16 866 describes an anchoring rod for use with synthetic resin which is provided at its front end with a head that is positionable in the vicinity of an undercut in the drilled hole as the anchoring rod is anchored. A positive engagement is thereby achieved in the region of the undercut, which enables tensile forces to be tolerated, even when a crack develops. The pull-out force, however, is largely based on the positive engagement in the undercut, so that in cracked concrete there is a considerable decline in the performance of the anchor. Furthermore, this known process requires a drilled hole with an undercut, the preparation of which requires special drilling tools.
EP-A-O 352 226 describes an anchoring means for anchoring in a cylindrical drilled hole including an anchoring rod provided with an end having an expansible cone. A parting agent is applied to the head and the shank of the anchoring rod which is intended to prevent the compounded mass from adhering to the anchoring rod. When a crack in the base occurs, the mortar compound becomes detached from the anchoring rod so that the bond between the mortar mass and the wall of the drilled hole is maintained. Subsequent slipping of the head of the anchoring rod provided with the expansible cone is intended to compensate for enlargement of the internal bore of the hardened mortar plug. When the anchoring rod is stressed, however, expansion forces are generated by the expansible cone expanding in the direction of the bottom of the drilled hole, which is precisely what is to be avoided in anchorings with composite anchors. Furthermore, there is a danger that the parting layer will be rubbed off or damaged as the composite anchor is driven in so that the desirable effect of subsequent slipping does not occur. |
Rude Cosmetics
Founded in 2016 in the heart of Downtown Los Angeles, CA, Rude Cosmetics was born to offer cutting edge, high quality cosmetics at a comfortable price. Our makeup allows for unapologetic self expression. To be bold, fierce, or even RUDE, without self-doubt because you are wearing MAKEUP WITH AN ATTITUDE. |
Out of my distress I called on the Lord; the Lord answered me and set me in a broad place. With the Lord on my side I do not fear. What can mortals do to me? Psalm 118:5-6
Whenever I read this verse it takes me back to a sermon I heard umpteen years ago. There used to be this thing about having three points all beginning with the same letter. The sermon outline was “The call, The cause and The consequence.”
So say what you like about artificial sermon structures or the dangers of over-alliteration, I can give testimony here and now that if you want to put a truth into peoples’ minds, the old three-point same letter routine certainly has staying power!
And since I can remember the outline, I have a pretty shrewd idea of the content too. The “call” in this case is my call; it’s a” turning to the Lord”. The cause of the call is evidently “my distress” and the consequence of the call is that the Lord answered me and set me in a broad place.
And whilst I still remember the framework of a sermon spoken to me as a child –I was probably about ten– I also remember the reality of the experience. It’s an experience that everyone has, sooner or later, and is explained succinctly in that word “distress.”
No one likes distress, and I guess advertising agencies make millions each year promoting the illusion of a distress-free existence. Whatever the issue, on a scale running from “tired hair” (low) to inner peace (high), we are promised a solution if only we buy their product.
The psalmist here (and the Bible en passant) offers an alternative therapy. If you’re in a tight spot, God offers a broad place; if you’re feeling threatened and intimidated, God offers to be on your side; if you feel overwhelmed with fear, God offers you the assurance of his presence.
Just a little while before (approximately) hearing the sermon, I had some issues with bullying at school. For some reason, I found it very difficult to tell my parents, and so it became a solitary distress. I can still remember the acuteness of the fear that took hold of me in certain areas of the school (the bus stop by the gate, the outside toilets). One day my brother noticed something, spoke to me about it and quietly made it his business to linger with me in those areas as best he could. The problem stopped.
All it took was the assurance of the presence of someone stronger than I…. I called out in my distress. He heard and answered. He brought me into a safe place.
Last week a close friend of mine lost a beloved nephew to suicide. He was 23. How my heart aches for those who are in distress and find no one to answer their heart’s call. |
aaxDriveManager 1.0.0
aaxDriveManager 1.0.0
The aaxDriveManager ActiveX Control is a component that gives you an easy access to manage disk and CDROM drives. With this component, you can: - Eject CD and media; - Query for drive types and availability; - Get drive capacity and free space; ... |
/*******************************
Copyright (c) 2016-2020 Grégoire Angerand
Permission is hereby granted, free of charge, to any person obtaining a copy
of this software and associated documentation files (the "Software"), to deal
in the Software without restriction, including without limitation the rights
to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
copies of the Software, and to permit persons to whom the Software is
furnished to do so, subject to the following conditions:
The above copyright notice and this permission notice shall be included in all
copies or substantial portions of the Software.
THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE
SOFTWARE.
**********************************/
#include "PropertyPanel.h"
#include "widgets.h"
#include <editor/context/EditorContext.h>
#include <external/imgui/yave_imgui.h>
namespace editor {
PropertyPanel::PropertyPanel(ContextPtr cptr) :
Widget(ICON_FA_WRENCH " Properties"),
ContextLinked(cptr) {
set_closable(false);
}
void PropertyPanel::paint(CmdBufferRecorder&) {
if(!context()->selection().has_selected_entity()) {
return;
}
ecs::EntityId id = context()->selection().selected_entity();
if(id.is_valid()) {
ImGui::PushID("widgets");
draw_component_widgets(context(), id);
ImGui::PopID();
}
}
}
|
Dai Shulun
Dai Shulun (, 732-789) was a Chinese poet of the mid-Tang period.
Biography
Dai Shulun, born in 732, was a native of Jintan, Runzhou (in today's Jiangsu). He served as a government official, however, in his later years, he was banished from the imperial court after the death of Emperor Daizong in 779. He then held various provincial positions, including a stint as the governor of Fuzhou, Jiangxi and as the frontier commissioner (经略使, jinglue shi) of Rongzhou (容州) in Guangxi. He was recalled ten years later back to the court, but died before he reached the capital in 789.
Works
Dai had ten collections of poetry published, but only two have survived to the present day. One of his poems was included in the important Qing-era anthology Three Hundred Tang Poems.
References
Bibliography
External links
Books of the Quan Tangshi that include collected poems of Dai Shulun at the Chinese Text Project:
Book 268
Book 269
Category:Tang dynasty poets
Category:8th-century Chinese poets
Category:Writers from Changzhou
Category:Politicians from Changzhou
Category:Tang dynasty politicians from Jiangsu
Category:Poets from Jiangsu
Category:Three Hundred Tang Poems poets |
Mental health, psychosocial support and the tsunami.
Disasters can have major impact on social and psychological functioning when individuals are exposed to these either indirectly or directly. The responses and coping strategies used by individuals are strongly influenced by cultural factors as well as social support and other factors. In this paper the challenges in planning and delivery of mental health services are described and suggestions put forward for preparedness of future disasters. In cultures which are kinship-based, the help may be available within kinship, and statutory services may rely on such systems. |
Newsletters
Events
Speech and Vision
After 40 years of humans serving computers, people are finally beginning to wake up and demand that the relationship be reversed: They want machines to become simpler, address human needs and help increase human productivity. That’s as it should be. With computer technology maturing, it’s high time, as we have repeatedly said in this column, for makers and users of computers to change their focus from machines to people.
But how do you make a machine simpler? With fewer controls? Not really. As you know from watches and other devices that have one mode-changing button and another to select functions within a mode, you can easily get lost in a confusion of modes and functions. Would machines be simpler if they had fewer capabilities? No! Imagine a car that can only do two things-go and turn right. This car can go anywhere, but you wouldn’t prefer it to your own car, which has more capabilities. What is it that we really want when we ask that our computers be easier to use?
True ease of use, as opposed to the perfunctory use of colors and floating animals to create the illusion of “user friendliness,” involves means of interaction that are natural to people and therefore require no new learning. Speech and vision are the two principal means we have used to interact with other people and the world around us for thousands of years. That should be enough of a clue to steer our attention to these two modes of interaction. And since vision occupies two-thirds of the human cerebral cortex, we may be tempted to declare it the queen of human-machine communication. That would be an easy-but deceptive-conclusion.
Vision and speech do not serve the same natural roles in communication. Being Greek, I can still hold a “conversation” in Athens, through a car window, using only gestures and grimaces-one clockwise rotation of the wrist means “how are you” while an oscillating motion of the right hand around the index finger with palm extended and sides of mouth drawn downward, means “so-so.” A sign language like ASL works even better. But when speech is available, it invariably takes over as the preferred mode of human communication.
That’s because among people, speech is used symmetrically for transmitting and receiving concepts. Visual human communication, on the other hand, is highly asymmetric-we can perceive a huge amount of information with our eyes, but can’t deliver equally rich visual information with gestures (visual communication would be more symmetric if we all sported display monitors on our chests). The power of vision in humans lies primarily in the one-way digestion of an incredible amount of information-nature’s, or God’s, way of ensuring survival in a world of friends and enemies, edible and man-eating animals, useful and useless objects, lush valleys and dangerous ravines, where maximum information was essential.
But then, why didn’t nature, or God, make speech just as asymmetric as vision? I’ll venture the guess that speaking and listening were meant for intercommunication rather than perception, where, unlike survival, symmetry was desirable. And since survival was more important than chatting, the lion’s share of the human brain was dedicated to seeing.
These conclusions run against the common wisdom that for human-machine communication, “vision is just like speech, only more powerful.” Not so! These two serve different roles, which we should imitate in human-machine communication: Spoken dialogue should be the primary approach for back-and-forth exchanges, and vision should be the primary approach for human perception of information from the machine.
We can imagine situations where a visual human-machine dialogue would be preferable, for example in learning by machine to ski or juggle. But we are interested in human-machine intercommunication across the full gamut of human interests, where, as telephony has demonstrated, speech-only exchanges go a long way. (Might these basic differences between speech and vision have contributed to the lack of success of video telephony?)
Finally, if we can combine speech and vision in communicating with our machines, as we do in our interactions with other people, we’ll be even better off. But that’s not easy to do yet, because the technologies for speech and vision are in different stages of development. Nor is the wish to combine them reason enough to ignore their different roles.
Conclusion: When you face a machine, instead of your surrounding world and other people, your interactions will be comparably natural, and the machine easiest to use, if it uses speech understanding and speech synthesis for two-way human-machine dialogue (these technologies have begun appearing commercially), and if it has large realistic displays that convey to you a great deal of visual information (as do today’s displays). As machine vision improves, it should be combined with speech for even more natural human-machine exchanges (such combined capabilities are now being researched and demonstrated in several research labs).
So, take heart: Simpler, more natural computer systems will enter our lives within the next 5 to 10 years. Let’s speed up their arrival, as users by asking for them, and as technologists by daring to build them. |
Capitol Quotes: February 8, 2013
“Ultimately, I’m concluding now that the gas tax is declining and dying and it’s never coming back.” — Sen. Steve Farley of Tucson, saying raising the gas tax isn’t the solution for Arizona’s transportation problems.
“Who’s going to want to put that on their social networking profile page?” — Attorney Hanni Fakhouri of the Electronic Frontiers Foundation, saying a bill to require registered sex offenders to divulge their crimes on their “About Me’’ profile would have a chilling effect on free speech.
“We like to be just left alone and ride our motorcycles.” — Paul “Sky Pilot” Price, a lobbyist with the Modified Motorcycle Association who supports a bill that would prohibit police from profiling motorcyclists.
“It’s very clearly a gray area.” — Rep. Martin Quezada, D-Phoenix, on whether lawmakers meeting in a hallway outside a hearing room constituted a violation of the state’s open meetings law.
“Pledges are a gimmick. Your actions speak louder than any pledge.” — Republican consultant Bert Coleman, saying he advises all his lawmaking clients not to sign any pledge such as never to increase taxes. |
14,000 Smuggled Pills Seized in Transit from Singapore to Mumbai
February 7, 2011
Indian Customs Official seized 14,000 misoprostol tables from a Mumbai resident who arrived at Chhatrapati Shivaji International Airport from Singapore on January 31, 2011.
Officers apprehended the suspect, Yusuf Masalawala, 54, while evading customs by going through the “green channel,” which indicates no customs declaration. Customs officials said that no medicine conveyed without declaration is allowed in such a large quantity because it is clearly beyond personal use, reported the Hindustani Times.
Customs authorities are concerned that the medicine, used to prevent deadly hemmoraging after childbirth, may be fake. “We are checking if these tablets are adulterated,” said the customs officials.
“Each year, 45 million women deliver without a skilled attendant, a situation in which the greatest number of maternal deaths occurs,” says World Health Organization experts, adding that “women can safely self-administer misoprostol orally to effectively prevent postpartum hemorrhage (PPH).” Dropping the rate of death in childbirth is central to the organization’s Millennium Development Goal to reducing maternal mortality by 75% between 1990 and 2015. |
No Money in Budget to Tackle Rape Kits
The state budget passed last week does not include money to tackle the huge backlog of untested rape kits, and the sponsors of legislation that would have set money aside to test the estimated 20,000 kits are not hopeful for relief this year. Rape victim Meaghan Ybos continues to tell her story to help push the legislation and eliminate the state's massive backlog, the Tennessean reports. She was raped in 2003, but her kit was not tested until almost a decade later when she called to check on her cold case after hearing about a possible serial rapist in her area. He was later convicted of raping Ybos and six other women. |
Expression of Candida albicans secreted aspartyl proteinase in acute vaginal candidiasis.
In order to analyze the in vivo expression of Candida albicans secreted aspartyl proteinases (SAP) in human vaginal infection, the vaginal secretion from 29 human subjects was collected by vaginal swab, and the expression of SAP1-SAP6 was detected by reverse-transcriptase polymerase chain reaction using specific primer sets. It was found that Sap2 and Sap5 were the most common genes expressed during infection; Sap3 and Sap4 were detected in all subjects and all 6 SAP genes were simultaneously expressed in some patients with vaginal candidiasis. It was suggested that the SAP family is expressed by Candida albicans during infection in human and that Candida albicans infection is associated with the differential expression of individual SAP genes which may be involved in the pathogenesis of vaginal candidiasis. |
Some computing systems implement translation software to translate portions of target instruction set architecture (ISA) instructions into native instructions that may be executed more quickly and efficiently through various optimization techniques such as combining, reorganizing, and eliminating instructions. More particularly, in transactional computing systems that have the capability to speculate and rollback operations, translations may be optimized in ways that potentially violate the semantics of the target ISA. Due to such optimizations, once a translation has been generated, it can be difficult to distinguish whether events (e.g., architectural fault such as a page violation) encountered while executing a translation are architecturally valid or are spuriously created by over-optimization of the translation. |
Taking a look at Ontario’s deficit and debt
Ontario faces a mountain of debt that is quickly climbing towards $312 billion dollars and over the next few years, both the Liberals and NDP have announced they will add to it by running deficits. But what does it all mean? And how does it affect you? Global’s Jamie Mauracher breaks down the province’s current financial situation in part one of our series, “Where They Stand.” |
Q:
How to integrate the infinitesimal spacetime interval?
Consider events A and B with coordinates $(t_A,x_A,y_A,z_A)$ and $(t_B,x_B,y_B,z_B)$ respectively.
The spacetime interval $\Delta s$ between them is given by $$\Delta s= \sqrt{c^2\Delta t^2-\Delta x^2-\Delta y^2-\Delta z^2}$$
where $\Delta t=t_B-t_A$ etc.
I am trying to prove that the spacetime interval $\Delta s$ can also be found by integrating the infinitesimal spacetime interval $ds$ using
$$\Delta s=\int^B_A ds$$
where $ds$ is given by
$$ds = \sqrt{c^2dt^2-dx^2-dy^2-dz^2}.$$
So I will have to integrate
$$\int^B_A ds = \int^B_A \sqrt{c^2dt^2-dx^2-dy^2-dz^2}.$$
How can this be integrated to show that $\int^B_A ds = \Delta s$?
A:
Generically, it isn't. $\int_A^B ds$ is the proper time elapsed along the worldline connecting $A$ and $B$, and its value depends very much on which worldline you choose. The $\Delta s$ you mention is the proper time along the straight line connecting the events, meaning that it is the proper time as measured by an inertial observer traveling between them.
Explicitly, let $x,y,$ and $z$ be functions of $t$. We then have
$$\int_{t_i}^{t_f}c\sqrt{1 - \frac{\dot x^2 - \dot y^2 - \dot z^2}{c^2}} dt$$
To go further, you need to specify what the functions $x,y,$ and $z$ are. In the simplest case, (that of constant velocity), one could have
$$ x(t) = x_i + \frac{(x_f - x_i)}{t_f-t_i} t =x_i +\overline v_x t$$
$$ y(t) = y_i + \overline v_y t $$
$$ z(t) = z_1 + \overline v_z t $$
from there, the integral becomes
$$\int_{t_i}^{t_f} c\sqrt{1-\frac{\overline v_x^2 + \overline v_y^2 + \overline v_z^2}{c^2}} dt = \int_{t_i}^{t_f} c\sqrt{1-\frac{\overline v^2}{c^2}} dt = c\Delta t \sqrt{1-\frac{\overline v^2}{c^2}} $$
$$= \sqrt{ c^2\Delta t^2 - \Delta x^2 - \Delta y^2 - \Delta z^2}$$
However, if you choose a different worldline connecting $A$ and $B$, this will no longer be true. As a good exercise, you might try the worldline you get by traveling at constant speed $2\overline v$ for half the time (assuming that $\overline v < c/2$, of course), and then sitting still for the remainder. This is not the worldline of an inertial observer, so we would expect the corresponding proper time to be smaller than before; indeed, you should find that
$$\Delta s=c \frac{\Delta t}{2}\sqrt{1-\frac{4\overline v^2}{c^2}} + c \frac{\Delta t}{2}$$
$$ = \sqrt{\frac{c^2\Delta t^2}{4} - \Delta x^2 - \Delta y^2 - \Delta z^2} + \frac{c \Delta t^2}{2} < \sqrt{c^2\Delta t^2 - \Delta x^2 - \Delta y ^2 - \Delta z^2}$$
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Saturday, June 25, 2016
Generative Adversarial Nets in TensorFlow (Part I)
This post was first published on 12/29/15, and has since been migrated to Blogger.
This is a tutorial on implementing Ian Goodfellow's Generative Adversarial Nets paper in TensorFlow. Adversarial Nets are a fun little Deep Learning exercise that can be done in ~80 lines of Python code, and exposes you (the reader) to an active area of deep learning research (as of 2015): Generative Modeling!
Scenario: Counterfeit Money
To help explain the motivations behind the paper, here's a hypothetical scenario:Danielle is a teller at a bank, and one of her job responsibilities is to discriminate between real money and counterfeit money. George is a crook and is trying to make some counterfeit money, becase free money would be pretty radical.
Let's simplify things a bit and assume the only distinguishing feature of currency is one unique number, $X$, printed on the each bill. These numbers are randomly sampled from a probability distribution, whose density function $p_{data}$ is only known to the Treasury (i.e. neither Danielle nor George know the function). For convenience, this tutorial uses $p_{data}$ to refer to both the distribution and the density function (though semantically a distribution and its density function are not the same).
George's goal is to generate samples $x^\prime$ from $p_{data}$, so his counterfeit currency is indistinguishable from "real" currency. You might ask: how can George generate samples from $p_{data}$ if he doesn't know $p_{data}$ in the first place?
We can create computationally indistinguishable samples without understanding the "true" underlying generative process [1]. The underlying generative process is the method that the Treasury itself is using to generate samples of $X$ - perhaps some efficient algorithm for sampling $p_{data}$ that relies on the analytical formula for the pdf.
We can think of this algorithm as the "natural (function) basis", the straightforward method the Treasury would actually use to print our hypothetical currency. However, a (continuous) function can be represented as a combination of a different set of basis functions; George can express the same sampler algorithm in a "neural network basis" or "Fourier basis" or other basis that can be used to build a universal approximator. From an outsider's perspective, the samplers are computationally indistinguishable, and yet George's model doesn't reveal to him the structure of the "natural" sampler basis or the analytical formula of $p_{data}$.
Background: Discriminative vs. Generative Models
Let $X$, $Y$ be the "observed" and "target" random variables. The joint distribution for $X$ and $Y$ is $P(X,Y)$, which we can think of as a probability density over 2 (possibly dependent) variables.
A Discriminative model allows us to evaluate the conditional probability $P(Y|X)$. For instance, given a vector of pixel values $x$, what is the probability that $Y=6$? (where "6" corresponds to the categorical class label for "tabby cat"). MNIST LeNet, AlexNet, and other classifiers are examples of a discriminative models.
On the other hand, a Generative model can allows us to evaluate the joint probability $P(X,Y)$. This means that we can propose value pairs $(X,Y)$ and do rejection-sampling to obtain samples $x$,$y$ from $P(X,Y)$. Another way to put this is that with the right generative model, we can convert a random number from $[0,1]$ into a picture of a rabbit. That's awesome.
Of course, generative models are much harder to construct than discriminative models, and both are active areas of research in statistics and machine learning.
Generative Adversarial Networks
Goodfellow's paper proposes a very elegant way to teach neural networks a generative model for any (continuous) probability density function. We build two neural networks $D$ (Danielle) and $G$ (George), and have them play an adversarial cat-and-mouse game: $G$ is a generator and attempts to counterfeit samples from $p_{data}$ and $D$ is a decider that tries to not get fooled. We train them simultaneously, so that they both improve by competing with each other. At convergence, we hope that $G$ has learned to sample exactly from $p_{data}$, at which point $D(x)=0.5$ (random guessing).
Advesarial Nets have been used to great success to synthesize the following from thin air:
In this tutorial we won't be doing anything nearly as amazing, but hopefully you'll come away with a better fundamental understanding of adversarial nets.
Implementation
We'll be training a neural network to sample from the simple 1-D normal distribution $\mathcal{N}(-1,1)$
Let $D$,$G$ be small 3-layer perceptrons, each with a meager 11 hidden units in total. $G$ takes as input a single sample of a noise distribution: $z \sim \text{uniform}(0,1)$. We want $G$ to map points $z_1,z_2,...z_M$ to $x_1,x_2,...x_M$, in such a way that mapped points $x_i=G(z_i)$ cluster densely where $p_{data}(X)$ is dense. Thus, G takes in $z$ and generates fake data $x^\prime$.
Meanwhile, the discriminator $D$, takes in input $x$ and outputs a likelihood of the input belonging to $p_{data}$.
Let $D_1$ and $D_2$ be copies of $D$ (they share the same parameters so $D_1(x)=D_2(x)$). The input to $D_1$ is a single sample of the legitimate data distribution: $x \sim p_{data}$, so when optimizing the decider we want the quantity $D_1(x)$ to be maximized. $D_2$ takes as input $x^\prime$ (the fake data generated by $G$), so when optimizing $D$ we want to $D_2(x^\prime)$ to be minimized. The value function for $D$ is:
$$
\log(D_1(x))+\log(1-D_2(G(z)))
$$
Here's the Python code:
The reason we go through the trouble of specifying copies $D_1$ and $D_2$ is that in TensorFlow, we need one copy of $D$ to process the input $x$ and another copy to process the input $G(z)$; the same section of the computational graph can't be re-used for different inputs.
When optimizing $G$, we want the quantity $D_2(X^\prime)$ to be maximized (successfully fooling $D$). The value function for $G$ is:
$$
\log(D_2(G(z)))
$$
Instead of optimizing with one pair $(x,z)$ at a time, we update the gradient based on the average of $M$ loss gradients computed for $M$ different $(x,z)$ pairs. The stochastic gradient estimated from a minibatch is closer to the true gradient across the training data.
The training loop is straightforward:
Manifold Alignment
Following the above recipe naively will not lead to good results, because we are sampling $p_{data}$ and $\text{uniform}(0,1)$ independently each iteration. Nothing is enforcing that adjacent points in the $Z$ domain are being mapped to adjacent points in the $X$ domain; in one minibatch, we might train $G$ to map $0.501 \to -1.1$, $0.502 \to 0.01$, and $0.503 \to -1.11$. The mapping arrows cross each other too much, making the transformation very bumpy. What's worse, the next minibatch might map $0.5015 \to 1.1$, $0.5025 \to -1.1$, and $0.504 \to 1.01$. This implies a completely different mapping $G$ from the previous minibatch, so the optimizer will fail to converge.
To remedy this, we want to minimize the total length of the arrows taking points from $Z$ to $X$, because this will make the transformation as smooth as possible and easier to learn. Another way of saying this is that the "vector bundles" carrying $Z$ to $X$ should be correlated between minibatches.
First, we'll stretch the domain of $Z$ to the same size of $X$. The normal distribution centered at -1 has most of its probability mass lying between $[-5,5]$, so we should sample $Z$ from $\text{uniform}(-5,5)$. Doing this means $G$ no longer needs to learn how to "stretch" the domain $[0,1]$ by a factor of 10. The less $G$ has to learn, the better.
Next, we'll align the samples of $Z$ and $X$ within a minibatch by sorting them both from lowest to highest.
Instead of sampling $Z$ via np.random.random(M).sort(), we'll use via stratified sampling - we generate $M$ equally spaced points along the domain and then jitter the points randomly. This preserves sorted order and also increases the representativeness the entire training space. We then match our stratified, sorted $Z$ samples to our sorted $X$ samples.
Of course, for higher dimensional problems it's not so straightforward to align the input space $Z$ with the target space $X$, since sorting points doesn't really make sense in 2D and higher. However, the notion of minimizing the transformation distance between the $Z$ and $X$ manifolds still holds [2].
This step was crucial for me to get this example working: when dealing with random noise as input, failing to align the transformation map properly will give rise to a host of other problems, like massive gradients that kill ReLU units early on, plateaus in the objective function, or performance not scaling with minibatch size.
Pretraining D
The original algorithm runs $k$ steps of gradient descent on $D$ for every step of gradient descent on $G$. I found it more helpful to pre-train $D$ a larger number of steps prior to running the adversarial net, using a mean-square error (MSE) loss function to fit $D$ to $p_{data}$. This loss function is nicer to optimize than the log-likelihood objective function for $D$ (since the latter has to deal with stuff from $G$). It's easy to see that $p_{data}$ is the optimal likelihood decision surface for its own distribution.
Here is the decision boundary at initialization.
After pretraining:
Close enough, lol.
Other Troubleshooting Comments
Using too many parameters in the model often leads to overfitting, but in my case making the network too big failed to even converge under the minimax objective - the network units saturated too quickly from large gradients. Start with a shallow, tiny network and only add extra units/layers if you feel that the size increase is absolutely necessary.
I started out using ReLU units but the units kept saturating (possibly due to manifold alignment issues). The Tanh activation function seemed to work better.
I also had to tweak the learning rate a bit to get good results.
Results
Before training, here is $p_{data}$, the pre-trained decision surface of $D$, and the generative distribution $p_g$.
.
Here's the loss function as a function of training iterations.
After training, $p_g$ approximates $p_{data}$, and the discriminator is about uniformly confused ($D=0.5$) for all values of $X$.
And there you have it! $G$ has learned how to sample (approximately) from $p_{data}$ to the extent that $D$ can no longer separate the "reals" from the forgeries.
Footnotes
Here's a more vivid example of computational indistinguishability: suppose we train a super-powerful neural network to sample from the distribution of cat faces.
The underlying (generative) data distribution for "true" cat faces involves 1) a cat being born and 2) somebody eventually taking a photograph of the cat. Clearly, our neural network isn't learning this particular generative process, as no real cats are involved. However, if our neural network can generate pictures that we cannot distinguish from "authentic" cat photos (armed with polynomial-time computational resources), then in some ways these photos are "just as legitimate" as regular cat photos.
This is worth pondering over, in the context of the Turing Test, Cryptography, and fake Rolexes.
Excessive mapping crossover can be viewed from the perspective of "overfitting", where the learned regression/classification function has been distorted in "contradictory" ways by data samples (for instance, a picture of a cat classified as a dog). Regularization techniques implicitly discourage excessive "mapping crossover", but do not explicitly implement a sorting algorithm to ensure the learned transformation is continuous / aligned in $X$-space with respect to $Z$-space. Such a sorting mechanism might be very useful for improving training speeds...
The inverse transform method converts a sample of Uniform(0,1) distribution into a sample of any other distribution (as long as the cumulative density function is invertible). There exists some function that maps (a sample from 0-1) to (a sample from the distribution of rabbit images). Such a function is highly complex and likely has no analytical formula, but a neural network can learn to approximate such a function.
The article mentions rejection sampling, which is a different technique that does not directly map from [0,1] to the sample of the target distribution. Thanks for helping me clarify this!
Great post, one short question. As far as I understood, it seems that the optimizer does not have to be subtracted from 1; e.g. opt_g=tf.~.minimize(1-obj_g,~) -> opt_g=tf.~.minimize(-obj_g,~), same for opt_d. Am I right? Is there any reason you have specified it to be 1? I am confused because, in the original paper, I could not find any mention about the 1 you have subtracted the objective functions from.
Hi everyone,I would like to ask a question about dcgan. When i try to generate a single image from a single z vector using generative model of dcgan, it produces an average image but i try to generate a batch of images from a batch of z vectors, it produces reasonable results. How can we generate a single image from a single z vector?
Thank you for the explanation. I'm doing some test with a similar code to the one that is in github because I need it for a project and I have a question:In the multilayer preceptron, why you choose the second dimension of the w1 as 6, and then the w2 dimensions as (6,5). Does it has something to do with the normal distribution? I'm doing test with other dimensions and if they are not too big the results are quite similar.Can anybody explain me why these dimensions are chosen? and why if I put much bigger dimensions the results are so bad?
Thanks for posting useful information.You have provided an nice article, Thank you very much for this one. And i hope this will be useful for many people.. and i am waiting for your next post keep on updating these kinds of knowledgeable things...Really it was an awesome article...very interesting to read..please sharing like this information......Android training in chennaiIos training in chennai |
The aim of this SBIR application is to develop a bead based array system for the specific detection and classification of microRNAs. The discovery of miRNAs representing a paradigm shift that suggested the existence of many unknown cellular function and regulation mechanisms. Already, miRNAs have been found implicated in different cancers and leukemia. MicroRNA has all the characteristics to become new class of biomarker for pharmaceutical applications. However, the existing methods for studying the expression of miRNA are labor intensive, time consuming, and also lacks the specificity and sensitivity. A more efficient and accurate research and development tool is much in demand. We have developed a bead array based method that integrated the xMPA technology platform with the LNA (locked nucleic acid) technology. The method, called xMAP-MP for xMAP based miRNA profiling, used beads coupled capture oligo and a biotin labeled detecting oligo to quantitatively detect and classify miRNA. With this method, multiple miRNAs can be studied together in one reaction. Preliminary studies have shown that the assay is highly specific and sensitive: miRNAs can be detected using only 100ng of total RNA. It detects mature miRNAs preferentially over precursor miRNAs. It could also provide more accurate quantitative measurement of miRNA levels. Phase I study allowed us identified unique miRNA distributions in 10 normal tissues as well as in 10 solid tumor tissues. A "signature" expression profile was identified for breast cancer. The xMAP-MP is also very efficient: samples do not need to be labeled; hybridization takes only 30 minutes; and detection and data acquisition takes only a minute. The entire procedure can be finished within an hour. Furthermore, the multiplex capability of the xMAP technology platform allows the study of up to 100 miRNAs in one assay. The proposed study has three specific aims: (1)Further develop and increase the coverage of detectable microRNAs. The current panels can detect 115 microRNA targets. We would like to expand the panels so that they can detect approximately 250 known microRNAs. (2)Use clinical samples and cancer cell lines to develop and evaluate "signature" panels for four malignancies, including breast cancer, prostate cancer, lymphoma, and glioma. (3) Prepare for commercialization by developing assay-specific software, and establishing GMP manufacture and quality control protocols. MicroRNA has all the characteristics to become the new class of biomarker for pharmaceutical applications. However, the existing methods for studying the expression of miRNA are labor intensive, time consuming, and also lacks the specificity and sensitivity. A more efficient and accurate research and development tool is much in demand. We have developed a bead array based method which allows multiple miRNAs to be studied together in one reaction. [unreadable] [unreadable] [unreadable] |
//
// GADMediationAdEventDelegate.h
// Google Mobile Ads SDK
//
// Copyright 2018 Google Inc. All rights reserved.
//
#import <GoogleMobileAds/GADAdReward.h>
#import <UIKit/UIKit.h>
/// Reports information to the Google Mobile Ads SDK from the adapter. Adapters receive an ad event
/// delegate when they provide a GADMediationAd by calling a render completion handler.
@protocol GADMediationAdEventDelegate <NSObject>
/// Notifies Google Mobile Ads SDK that an impression occurred on the GADMediationAd.
- (void)reportImpression;
/// Notifies Google Mobile Ads SDK that a click occurred on the GADMediationAd.
- (void)reportClick;
/// Notifies Google Mobile Ads SDK that the GADMediationAd will present a full screen modal view.
- (void)willPresentFullScreenView;
/// Notifies Google Mobile Ads SDK that the GADMediationAd failed to present with an error.
- (void)didFailToPresentWithError:(nonnull NSError *)error;
/// Notifies Google Mobile Ads SDK that the GADMediationAd will dismiss a full screen modal view.
- (void)willDismissFullScreenView;
/// Notifies Google Mobile Ads SDK that the GADMediationAd finished dismissing a full screen modal
/// view.
- (void)didDismissFullScreenView;
@end
/// Reports banner related information to the Google Mobile Ads SDK from the adapter.
@protocol GADMediationBannerAdEventDelegate <GADMediationAdEventDelegate>
/// Notifies Google Mobile Ads SDK that an action on the GADMediationAd will cause the application
/// to move into the background.
- (void)willBackgroundApplication;
@end
/// Reports interstitial related information to the Google Mobile Ads SDK from the adapter.
@protocol GADMediationInterstitialAdEventDelegate <GADMediationAdEventDelegate>
/// Notifies Google Mobile Ads SDK that an action on the GADMediationAd will cause the application
/// to move into the background.
- (void)willBackgroundApplication;
@end
/// Reports native related information to the Google Mobile Ads SDK from the adapter.
@protocol GADMediationNativeAdEventDelegate <GADMediationAdEventDelegate>
/// Notifies Google Mobile Ads SDK that the GADMediationAd started video playback.
- (void)didPlayVideo;
/// Notifies Google Mobile Ads SDK that the GADMediationAd paused video playback.
- (void)didPauseVideo;
/// Notifies Google Mobile Ads SDK that the GADMediationAd's video playback finished.
- (void)didEndVideo;
/// Notifies Google Mobile Ads SDK that the GADMediationAd muted video playback.
- (void)didMuteVideo;
/// Notifies Google Mobile Ads SDK that the GADMediationAd unmuted video playback.
- (void)didUnmuteVideo;
/// Notifies Google Mobile Ads SDK that an action on the GADMediationAd will cause the application
/// to move into the background.
- (void)willBackgroundApplication;
@end
/// Reports rewarded related information to the Google Mobile Ads SDK from the adapter.
@protocol GADMediationRewardedAdEventDelegate <GADMediationAdEventDelegate>
/// Notifies the Google Mobile Ads SDK that the GADMediationAd has rewarded the user with a reward.
- (void)didRewardUserWithReward:(nonnull GADAdReward *)reward;
/// Notifies Google Mobile Ads SDK that the GADMediationAd started video playback.
- (void)didStartVideo;
/// Notifies Google Mobile Ads SDK that the GADMediationAd's video playback finished.
- (void)didEndVideo;
@end
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Antonio Loro is an urban planner who focuses on the planning implications of emerging road vehicle automation technologies. He has conducted research with TransLink and Metrolinx on the potential impacts of automated vehicles, and is currently with the Ministry of Transportation of Ontario. This article was written by Antonio Loro in his personal capacity. The views expressed in this article are the author's own and do not necessarily represent the views of the previously mentioned organizations.
As efforts to develop automated vehicles continue to speed forward, researchers have begun to explore how driverless taxis in particular could play a prominent role in the future mix of urban transportation options. Some of these early findings raise the provocative argument that driverless taxis (or self-driving or fully-automated taxis, if you prefer) could hugely reduce or even eliminate the need for buses and trains. However, careful interpretation of this research reveals that vehicles with high passenger capacities (bus and rail transit, in other words) could be superseded by lower-capacity vehicles only where there is plenty of road space to spare. Where road lanes are in shorter supply, buses and trains – which could themselves get a huge productivity boost from automation – will continue to be indispensable for moving large volumes of passengers. In such cases, driverless taxis, especially share taxis, will be ideally suited to complement higher-capacity transit, generally by focusing on areas with a surplus of road space. And in the near-term, even before such advanced automation is perfected, automated buses could start improving mobility for large numbers of urban travelers.
Researchers have begun to explore future scenarios where vehicle automation technologies have advanced to a level that enables taxis to drive without human intervention through the full network of urban roads. Recently, the ITF (International Transport Forum), a think tank within the OECD, modeled a number of scenarios to examine how these driverless taxis, once they are commonplace, could serve urban travelers on a typical weekday in Lisbon. Among the outputs of their model, one is particularly attention-grabbing: even in a scenario where 8% of trips go by foot or bike, none go by transit, and the remaining 92% go by driverless taxis that serve single passengers, ITF researchers say that the number of taxis needed would be less than a quarter of the number of cars currently in use in the Portuguese capital. Such a reduction in the size of the overall fleet of cars in the city would greatly diminish parking demand. Unsurprisingly, though, in order to serve so many trips, the fleet of taxis would be used very intensively, and the total vehicle kilometres traveled (VKT) in the city would more than double.
Remarkably, the ITF team say that despite the upsurge in VKT in this scenario, travel times would be slowed very little. Underpinning this result is a noteworthy assumption in the model: currently, according to the ITF researchers, less than 40% of available capacity on Lisbon’s roads is in use during peak periods. (The authors caution that their figures are underestimates, as they do not account for bus travel, which makes up 13% of VKT in Lisbon.) The upshot is that even in a scenario where new taxi trips and empty taxis driving to their next passengers cause VKT to double, the ITF model’s outputs suggest that there should be road capacity to spare.
The model shows the previously very lightly used local roads absorbing much of the new VKT. Meanwhile, the most heavily traveled category of roads (“local traffic distributor roads”) rises from 43% to 69% of road capacity used. That 69% doesn’t necessarily mean traffic will be flowing smoothly, however. These percentages refer to the average capacity in use on different categories of roads – even if there is a low percentage of capacity in use on a given category of road, there could nevertheless be congestion focused at some locations on those roads. Interestingly, according to the TomTom Traffic Index, congestion may already be an issue in Lisbon, as travel times during peak periods are currently 45% to 70% longer than they would be under free-flow conditions.
The crucial implication to highlight here is that single-passenger driverless taxis could supplant buses and trains – but only where the roads have the capacity to absorb potentially huge increases in traffic without becoming congested.
A 2014 study by the Singapore-MIT Alliance for Research and Technology (SMART) arrived at results similar to those in the ITF study, though the SMART team modeled travel speeds in a much simpler way. The SMART researchers examined a scenario with single-passenger driverless taxis (or car-share vehicles) serving all trips in Singapore. They concluded that a fleet sized at one-third of the total number of passenger vehicles currently in use in the city could serve all trips while keeping peak period waiting times for the average passenger under 15 minutes. Such a dramatic result follows from a simplifying assumption in the model: the SMART team first estimated the current average speed that taxis drive at – including both the denser and the more dispersed areas of the city – and then assumed that future driverless taxis would drive at that particular speed, regardless of their location in the road network.
Less optimistically, the taxis would be bogged down in congestion of their own making. Currently in Singapore, 63% of peak period trips go via public transit. Shifting all of those trips to taxis would generate an abundance of new VKT – including VKT produced by empty taxis moving to their next passengers. Currently, peak period travel times on Singapore’s roads are 50% to 80% longer than they would be under free-flow conditions, according to TomTom; a massive increase in VKT wouldn’t help much.
A more recent article from the SMART team includes a brief exploration of the congestion effects of empty taxis repositioning themselves in a very simple road network. They find that their algorithm generally results in the empty vehicles traveling mainly on less busy roads, though the repositioning process could cause heavy congestion in networks where there is already congestion. This preliminary analysis suggests that much of the traffic produced by driverless taxi repositioning could be focused on the roads that are least congested to begin with. This suggestion lines up with the results of the ITF team. Interestingly, the ITF’s model of Lisbon has the biggest increases in traffic showing up on local streets in particular – which could unfortunately make them less attractive places to live, the authors caution. Such streets serve purposes other than being conduits for cars – they may be quiet routes for walking and cycling, or safe places for children to play, or inviting public spaces, for example – so injecting new car traffic could produce impacts other than congestion that are worth considering. Furthermore, while the SMART team suggests that much of the traffic created by repositioning per se might be focused on the roads that were previously least congested, the taxis that are actually carrying passengers could of course be the more important source of congestion – especially when large mode shifts, such as those seen in the scenarios described above, inevitably produce large VKT increases.
The ability of automated vehicles to use roads more efficiently could mitigate congestion resulting from increased VKT – with some caveats. Combining automation and V2V (vehicle-to-vehicle communication) technologies would enable vehicles to drive safely with short following gaps. However, the large potential capacity increases resulting from this “platooning”, where vehicles are grouped into closely-packed files, would mainly materialize on freeways, where traffic flows are less turbulent than on city streets. Automation with V2V could also boost flows through intersections by coordinating the movements of vehicles far more efficiently than traffic signals. These improvements would be constrained, though, wherever intersections are shared with entities not equipped with the requisite tech – not just cars, but pedestrians and cyclists as well. More radically, vehicles themselves could be smaller, thus occupying less road space, if the crash avoidance capabilities of automation eliminate the need for bulky, crashworthy construction. However, such a revolution in vehicle design would not be able to take over the streets until automation technologies are advanced enough and adopted widely enough to guarantee occupant safety.
The capacity limits of roads could be less of an impediment for multi-passenger driverless taxis. Hypothetically, if 8% of trips in Lisbon were taken on foot or bike and the remaining 92% were served by driverless taxis carrying multiple passengers (most commonly three to five, but as many as eight), the ITF team estimates peak period VKT would rise by 25%. It’s a substantial increase, but much smaller than the 103% jump in the single-passenger taxi scenario discussed above. Not surprisingly, providing public transit service would further mitigate VKT. In a scenario where 22% of trips go by subway, 8% go by foot or bike, and the remaining 70% go by driverless share taxi, the model estimates peak period VKT would rise by a relatively modest 9%.
Taxis serving multiple rather than single passengers would also mean an even smaller taxi fleet would suffice. Fewer cars in the city, kept busy serving dozens of trips a day, would drastically cut the need for parking. Sidewalks and bike lanes would be among the potential uses for the freed-up land. If taxi passengers share rides, and if 22% of trips go by public transit, the ITF figures that close to 95% of all parking spaces in Lisbon could be made redundant. (This outcome depends on traffic still flowing smoothly despite a 9% increase in VKT – if traffic is slowed, a larger taxi fleet would be needed to effectively serve all trips, so more parking would be needed during periods of low demand).
The discussion above just scratches the surface of the ITF and SMART studies – it’s definitely worth reading the original articles to explore their insights and to understand how the models were constructed. Higher-fidelity models that build on the ITF and SMART efforts will improve our estimates of the potential for driverless taxis to serve urban trips; however, even without complex models, it is clear that automation won’t eliminate the need for buses and trains when large numbers of people have to move through limited space. This is one of the straightforward geometric arguments that Jarrett has made before in this blog: larger vehicles fit more people into a given length and width of right-of-way than convoys of small vehicles can carry. (To illustrate, a freeway lane might have a capacity as high as 2400 cars per hour, while Bogotá’s TransMilenio bus rapid transit system has a capacity of 45,000 people per hour per direction.)
Of course, it’s a contentious question when we will attain the holy grail of automation technology sufficiently sophisticated to enable taxis or other vehicles to drive on any road in any conditions. It may appear further in the future than some suppose; nevertheless, even before this “Level 5” technology (as defined by the Society of Automotive Engineers) is mature, there will be vehicles capable of fully automated operation under more restricted conditions. There already are – such “Level 4” vehicles are currently capable of driving themselves at low speeds when segregated from challenging traffic environments. Beginning in the near-term, these kinds of low-speed automated vehicles, perhaps looking something like Google’s famously cute prototype, could carry passengers in settings like retirement communities. They could also circulate through networks of low-speed roads in suburban neighbourhoods or business parks to provide “first and last mile” access to and from transit routes.
Both in the near-term and the long-term, one of the most effective ways to reap the mobility benefits of automation will be to apply it to buses. Even with current technology, driverless operation would be feasible for buses running on busways with adequate exclusion of other vehicles and potential hazards. And even for buses on streets with mixed traffic, some of the technical challenges of achieving full automation are eased. For example, since bus routes run along only a small subset of the larger urban road network, the challenges of building and maintaining exquisitely detailed, meticulously annotated, continually updated maps would be substantially reduced – this would be advantageous for mapping-reliant approaches to automated driving, such as Google’s approach. The drop in labour costs from automation would enable dramatically increased frequencies, and the precision of automated control could also improve reliability. Because of the imminent potential to significantly improve mobility for large numbers of travelers, buses are a key priority for the application of automation.
With Level 5 automation, driverless taxis would become feasible. But rather than usurping the place of buses, they could play a complementary role. Level 5 would of course expand the domain of driverless buses, enabling them to provide service on any road; but it’s simply because buses can move numerous passengers in little road space that they will remain indispensable. Buses could ply heavily traveled corridors; driverless taxis could operate in less dense areas and during periods of lighter travel, whether serving complete trips or feeding into bus and train networks.
Interestingly, since low labour costs for driverless buses would enable higher frequencies, smaller vehicles would suffice to provide effective service in some areas. At a certain point, it could be difficult to distinguish in appearance between a small driverless bus and a driverless share taxi. However, their functions could be distinct: for example, driverless buses could provide frequent, predictable service on fixed routes according to schedules or headways, and driverless share taxis could provide on-demand, flexible route service. On the other hand, because diverting routes to pick up and drop off multiple passengers at numerous origins and destinations would cut into the travel time and cost benefits of taxi travel, some driverless share taxis could end up providing service with more fixed routing.
The take-home message from all this is that it’s critical to strategically deploy vehicle automation technologies according to their strengths and weaknesses. At some point, Level 5 automation will be achieved and driverless taxis will become feasible – but it’s important to think beyond just driverless taxis. To create the best possible mix of urban transportation options, it’s essential to consider the advantages and disadvantages of a range of potential automated vehicles and services – including buses, driverless taxis, and low-speed vehicles. Even more important, there's no need to wait for a Level 5 world with fully-fledged driverless taxis to appear before reaping the benefits of automation – and transit agencies have an opportunity to take the lead.
[My thoughts on this piece are at the top of the comments! — Jarrett]
Photo: Rotterdam driverless bus prototype, 2getthere.eu |
New vinegar produced by tomato suppresses adipocyte differentiation and fat accumulation in 3T3-L1 cells and obese rat model.
There is an increasing surplus of tomatoes that are abandoned due to their failure to meet customer standards. Therefore, to allow both value additions and the effective reuse of surplus tomatoes, we developed tomato vinegar (TV) containing phytochemicals and evaluated its anti-obesity effects in vitro and in vivo. TV inhibited adipocyte differentiation of 3T3-L1 preadipocyte and lipid accumulation during differentiation. TV supplementation in rats fed a high-fat diet (HFD) markedly decreased visceral fat weights without changing the food and calories intakes. TV significantly decreased hepatic triglyceride and cholesterol levels compared to the HFD group. Furthermore, TV lowered plasma LDL-cholesterol level and antherogenic index compared to the HFD group, whereas elevated HDL-cholesterol to total cholesterol ratio. These results show that TV prevented obesity by suppressing visceral fat and lipid accumulation in adipocyte and obese rats, and suggest that TV can be used as an anti-obesity therapeutic agent or functional food. |
KT Rolster announced that the team has not renewed contracts with Rush, Pawn, Ucal and Deft. The players are now free agents.
KT Rolster met an unfortunate end to 2018 World Championship, losing to iG in a close-5-game series. Earlier in the month, KT also parted ways with its support player, Mata. With most of the team’s starting members now free agents, it is now unclear which direction the rest of the players will take. |
Q:
Let $a$ and $b$ be real numbers. Then $\left( a+b\right) ^{3}=a^{3}+b^{3}$ implies $a=0$ or $b=0$.
My proof. We need to show that $a=0$ or $b=0$ for the equation.
We have,
$\left( a+b\right) ^{3}=a^{3}+3a^{2}b+3ab^{2}+b^{3}$ (by the binomial theorem)
$=a^{3}+b^{3}$ (by the assumption).
Now, adding $(-(a^{3}+b^{3})$ both sides yields $3a^{2}b+3ab^{2}=0$, i.e., $3ab\left( a+b\right) =0$ (by the distributive law). Since $3ab\left( a+b\right) =0$, $3ab=0$ or $(a+b)=0$, i.e., $a=0$ or $b=0$.
Can you check my proof?
in addition, Let $a$ and $b$ be real numbers. Then $\left( a+b\right) ^{3}=a^{3}+b^{3}$ implies $a=0$ and $b=0$.
So, how can I show this?
A:
What you are trying to prove is not true. For instance, let $a=1$ and $b=-1$, then $(a+b)^3=a^3 + b^3=0$.
The final conclusion of your attempted proof is incomplete, because $3ab(a+b) = 0$ implies that $a=0$ or $b=0$ or $a=-b$.
The case where $a=-b$ can be eliminated if you restrict $a$ and $b$ to be nonnegative. Thus, if $a,b \geq 0$ your proof is correct.
|
Q:
Orcacle Apex Trigger
I have a notes form which i am calling on two different pages and storing data in the same table on page one the parameter is p4_clid and on page 2 it is p21_entity. when i enter data on page one the data gets inserted but on page two it does not, how do i pass my page two parameter in trigger.
create or replace TRIGGER "BI_f_41"
before insert or update on "f_41"
for each row
begin
if inserting and :new.FORMRESPONSEID is null then
select "NEW_F41_SEQ".nextval
into :new.FORMRESPONSEID
from dual;
end if;
if inserting then
:new.SubjectID := get_subidn(v('P4_CLID')) ;
:new.FORMID := 41 ;
:new.subjecttypeid := 1 ;
:new.responseCreatedDate := localtimestamp;
:new.ProgramID := get_pgmid(v('P4_CLID')) ;
:new.AuditStaffID := v('SESSION_GIHUID');
:new.AuditDate := localtimestamp;
end if;
if updating then
:new.AuditDate := localtimestamp;
end if;
end;
A:
To answer your specific question, you could I suppose do this in your trigger:
Wherever you have:
v('P4_CLID')
Replace by:
case [something that indicates the calling page]*
when 4 then v('P4_CLID')
when 21 then v('P21_ENTITY')
end
(* I was going to say nv('APP_PAGE_ID') but that will always return the ID of your form page, so that won't work.)
I have to agree with the comment that said your approach is not correct.
The normal approach is to have a hidden item in your form page - let's say your form page is page 33 and the item is P33_ID. When you call the form from page 4 you pass in the value of P4_CLID in the URL:
f?p=...:P33_ID,...:&P4_CLID,...
From page 21 you pass in the value of P21_ENTITY instead:
f?p=...:P33_ID,...:&P21_ENTITY,...
You then use the value of P33_ID in your INSERT statement directly - not in a database trigger.
It is generally bad practice to have dependencies on APEX session state within database code including triggers, because it assumes that the one and only way the data can ever be inserted/updated/deleted is via your APEX application. That may be true for you now, but it is not future-proof.
|
Israeli Company to Dig for Uranium in the Negev
Studies say that there is uranium under the Negev - and Gulliver Energy intends to dig it up.
Contact Editor
David Lev, 22/12/11 11:36
Mining operation (illustrative)
Morguefile
The Water and Energy Ministry (formerly the National Infrastructures Ministry) is set to grant a license to Gulliver Energy to search for uranium in the Negev. This is the first time uranium mining will be taking place in Israel. The chairman of Gulliver Energy (formerly known as Urieli) is former Mossad chief Meir Dagan.
The uranium search will center on an area in the southern Negev, where oil exploration is being conducted by the Zerach exploration company. That exploration is taking place near the Dead Sea, at the Maya exploration site, south of Tzuk Tamrur, another exploration site near Arad. The license to be granted to Gulliver will allow the company to conduct tests and set up several drilling projects in the area, southwards toward the town of Sedom. The Ministry said that Gulliver had informed it that seismic and other tests indicated that there was a "strong likelihood" that uranium and other materials would be found at the site.
According to the Ministry, Gulliver asked for the license after several test wells in the area – where Zerach and several other companies are searching for oil – indicated that there was a large amount of radioactive material there, at levels relatively close to the surface. Numerous rocks with “high radioactive qualities,” the Ministry said, have been found in the test wells, indicating that there was a good possibility of numerous elements – including uranium – below ground. The Ministry said that Gulliver intended to bring in experts from abroad to help with the search.
The Ministry added that a special permit was needed because of the proximity of the search site to several nature preserves, and the sensitivity of the matter.
Gulliver last year signed an agreement with Zerach to acquire from the company all data on uranium and other materials discovered in the area. In return, Zerach will receive 12.5% of proceeds from the sale of uranium by Gulliver, if such sales ever take place. |
Biking vacations may be ticket for active travelers
April 22, 2011|By Georgina Cruz, Special Correspondent
Travelers who would enjoy seeing the sights from a vantage point close to the ground and with a breeze on their faces may wish to check out the many opportunities offered by bicycle tour companies on several continents. Cyclists usually enjoy a camaraderie that results from sharing an off-the-beaten path adventure with others in a group, and often find that getting there by bike is all the fun.
If going by bicycle appeals to you, here is a selection of programs available this season. Generally, bicycle tours provide a bicycle for use during the program, guides, a support vehicle, luggage service and cover fees related to sightseeing. Tour operators give information on terrain difficulty and the number of miles cyclists will cover each day. Many meals, including breakfasts, dinners and some lunches are usually included in the tour price as is lodging. For additional details on a particular program, contact the specific company you are interested in.
-- Austin-Lehman Adventures, an active travel company offering programs in Yellowstone National Park, Europe Africa and other locales, is featuring two new cycling explorations in Europe. One of the programs is a Tyrol Bicycle Tour from Innsbruck, Austria to Lake Garda. This tour is mostly downhill or flat with views of the Dolomites, castles and churches. Participants sip regional wines and dine on local fare. Tour dates are May 21-30, June 18-27 and Sept. 3-12. Per person, double occupancy rate is $4,598 ($980 single supplement). Another new program from Austin-Lehman is a Tuscany Bike Tour. A more challenging ride, it begins in Florence and takes in Chianti vineyards, Siena San Gimignano and other sights. A six-night/seven-day tour, it has departures scheduled in April, May, June, September and October. Cost is $3,398 per person, double ($680 single supplement). Visit www.austinlehman.com.
-- Backroads, an active travel company, is offering a Vineyards & Andean Culture Off the Beaten Path in Northern Argentina. The biking program takes in views of the Patagonian Steppe and the Andes. Participants will ride through high altitude valleys, canyons, subtropical forests and a cactus national park, experience gaucho culture, and become acquainted with the wines and food of the region. Meeting/departure point is Salta, Argentina. A seven-night/eight-day tour, prices range from $4,598 to $4,798 per person, double ($920 single supplement). Departures are slated for Nov. 6 and 27. Visit www.backroads.com.
-- ExperiencePlus! Bicycle Tours, a company that features bicycle tours on five continents, is offering two departures of a new cycling adventure across the Scottish Highlands. The eight or 11-day programs feature time to sample freshly smoked salmon, ales and whisky while pedaling by the heather from the North Sea to the Atlantic. Departures are July 3 and Sept. 4 and arrival/departure cities can be either Glasgow or Edinburgh. The eight-day Bicycling Scotland's Highlands Coast to Coast cover 229 miles, averaging 33 to 45 miles a day. Per person, double rate is $3,895 (single supplement is $600). The 11-day Bicycling Scotland's Highlands Coast to Coast Plus! The Isle of Skye trip covers 364 miles and extends by a ferry ride an adventure in the Hebrides. Rate is $5,245 per person, double (single supplement is $900). Visit www.experienceplus.com.
-- Summer Feet Cycling Vacations offers a varied menu of bike tours including three, six and seven-day bike tours featuring Arcadia National Park and other park areas. The company also offers custom programs, self-guided tours and a camping version of one of its trips. One offering is a six-day cycling vacation, Maine's Gold Coast, taking in Camden and Acadia National Parks. Departures are slated in June, July, August, September and October. Cost is $2,195 per person (single supplement is $500). Visit www.summerfeet.net. |
Introduction {#sec1}
============
Pancreatic cancer is a disease in which malignant (cancer) cells form in the tissues of the pancreas. It is currently one of the deadliest of the solid malignancies, whose incidence and death rates are increasing consistently during the past 30 years.[@bib1], [@bib2] Worldwide, the incidence ranges from 1 to 10 cases per 100,000 people, and it is generally higher in developed countries and among men.[@bib3], [@bib4] It was predicted that pancreatic cancer will become the second leading cause of cancer-related death by 2030 in the United States, ranking second only to lung cancer.[@bib1], [@bib5] Pancreatic cancer typically does not cause symptoms until it has grown, so it is most frequently diagnosed in advanced stages rather than early in the course of the disease.[@bib4] As a result, the cancer often has metastasized to other organs with very poor prognosis. There are various treatments for pancreatic cancer, including surgery (resection), chemotherapy, and chemoradiotherapy.[@bib4] However, present therapeutic strategies have not substantially improved the survival of patients over the past several decades, revealed by its resistance to the therapy, that more than 80% of patients relapse after resection, and that the 5-year survival rate has remained at only ∼5%.[@bib6] Therefore, new treatments are urgently needed for patients with pancreatic cancer.
RNAi is a fundamental pathway in eukaryotic cells by which small interfering RNA (siRNA) is able to mediate targeted mRNA transcript cleavage, repress gene expression, and compromise gene function within living cells.[@bib7] Given the ability to knock down, in essence, any gene of interest, RNAi via siRNAs has generated a great deal of interest in both basic research and clinical application. siRNA-based therapeutics[@bib7], [@bib8], [@bib9], [@bib10], [@bib11] have shown promise for treating genetic diseases (e.g., transthyretin amyloidosis, hemophilia, and porphyria), metabolic diseases (e.g., hypercholesterolemia), virus infection diseases (hepatitis B virus \[HBV\], Ebola, HIV, and RSV \[respiratory syncytial virus\]), ophthalmic diseases (non-arteritic anterior ischemic optic neuropathy \[NAION\], age-related macular degeneration \[AMD\], and diabetic macular edema \[DME\]), and various solid tumors (e.g., hepatocellular carcinoma, melanoma, and pancreatic cancer). siRNA therapeutics for oncology that have entered clinical trials include ALN-KSP, CALAA-01, TKM-PLK1, Atu027, DCR-MYC, SiG12D-LODER, and siRNA-EPHA2-DOPC.[@bib12] In addition, siRNA has been used to circumvent multiple drug resistance (MDR), to enhance the chemosensitivity of tumor cells to chemotherapeutics.[@bib13], [@bib14], [@bib15], [@bib16] siRNA nanoplexes also have been administered sequentially with conventional chemotherapeutics in order to block multiple signaling networks simultaneously.[@bib17], [@bib18]
Ribonucleotide reductase (RR) is a rate-limiting enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides, which is essential for DNA synthesis and replication.[@bib19] Human RR consists of two subunits, RRM1 and RRM2, and the expression of both proteins is required for enzymatic activity. In mammalian cells, RRM2 is expressed only in the late G1 or early S phase of the cell cycle, whereas the levels of RRM1 remain relatively consistent throughout the cell cycle.[@bib20], [@bib21] It was demonstrated that elevated RRM2 activity played a pivotal role in cellular response to DNA damage, tumor progression and invasion, angiogenesis, and the increase in drug-resistant properties.[@bib22], [@bib23], [@bib24], [@bib25] Overexpression of RRM2 is observed in many kinds of human cancers. It was identified as a diagnostic marker and an established anti-cancer therapeutic target.[@bib26], [@bib27] Moreover, it was reported that CALAA-01, a tumor-targeted nanodrug containing anti-RRM2 siRNA, mediated effective gene silencing in human beings and alleviated the symptom of melanoma.[@bib28] It was also observed that siRNA targeting RRM2 could be used for treating head and neck cancer[@bib29] (including oral squamous cell carcinoma[@bib30]), ovarian cancer,[@bib31] gastric adenocarcinoma,[@bib32] hepatocellular carcinoma,[@bib33] colorectal cancers,[@bib34] etc. Hence, siRNA against RRM2 displayed versatile anti-tumor activity in various solid tumors.
In this study, we explored the anti-tumor effect of siRNA against RRM2 on PANC-1, a human pancreatic carcinoma and epithelial-like cell line. 23 siRNAs targeting RRM2 were designed and screened. One of them (siRNA-04M) was finally selected, termed siRRM2, and used in the following experiments. The influences of siRRM2 on cell morphology, colony formation, and cell-cycle arrest were evaluated. By combining with doxorubicin (DOX), a well-defined anti-tumor chemotherapeutic, the siRNA's performances on cell proliferation (*in vitro*) and tumor growth (*in vivo*) were further investigated.
Results {#sec2}
=======
siRNA Activity Screening and Stability Evaluation {#sec2.1}
-------------------------------------------------
23 siRNAs targeting RRM2 (numbered from siRNA-01 to siRNA-23) were designed and selected with a high-throughput screening system called siQuant.[@bib35] For the first round of screening, 23 siRNAs were respectively transfected into HEK293A cells with lipofectamine 2000 at 1 nM. As a result, 14 of them displayed more than 80% silencing efficiency, and 8 of them showed approximately 90% knockdown efficiency ([Figure 1](#fig1){ref-type="fig"}A). Then three siRNAs (siRNA-04, siRNA-13, and siRNA-18) were selected to perform the second round of screening at three transfection concentrations of 1, 0.1, and 0.05 nM. It was observed that siRNA-04 achieved higher gene-silencing efficiency at the lowest transfection concentration (0.05 nM) ([Figure 1](#fig1){ref-type="fig"}B).Figure 1siRNA Screening and Activity Validation(A) The first round selection of 23 siRNAs at 1 nM with siQuant in HEK293A. (B) The second round selection of 3 siRNAs at three transfection concentrations of 1, 0.1, and 0.05 nM. (C) RRM2 mRNA expression of PANC-1 after being treated with siRNA-04M at 20 and 50 nM. NC and PC represent negative control (a scramble siRNA) and positive control (an siRNA showing good gene-silencing efficiency), respectively. Data were shown as mean ± SD. \*p \< 0.05, n = 3.
To stabilize the siRNA, precise chemical modifications with methoxy group and/or fluorine at 2′ of riboses of certain nucleotides were introduced to the siRNAs (as shown in our patent application file[@bib36]). RNase-resistant assay was performed to evaluate their stability in serum ([Figure S1](#mmc1){ref-type="supplementary-material"}). Data showed that both full-length and truncated versions of siRNA-04 without chemical modification were observed within 24 hr. Unfortunately, we failed to observe the full-length siRNA-04 without modification when incubating for 48 and 72 hr. In contrast, siRNA-04M with stabilization modification chemistry was resistant to RNase attack in serum, as siRNA still remained in full length even after 72-hr incubation. Hence, siRNA-04 itself is stable to some extent, and chemical modification further enhances its stability significantly.
Furthermore, to validate the siRNA's silencing activity against the endogenous targeting mRNA, instead of the sequence on the luciferase reporter system, and to evaluate the influence of chemical modification on the siRNA's potency, chemically modified siRNA-04 (siRNA-04M) was transfected into PANC-1 cell, a human pancreatic carcinoma and epithelial-like cell line, and mRNA expression was analyzed with real-time qPCR. Data demonstrated that siRNA-04M effectively inhibited the expression of RRM2 mRNA at the concentrations of 20 and 50 nM ([Figure 1](#fig1){ref-type="fig"}C).
On-Target Activity and Off-Target Effect of Anti-RRM2 siRNAs {#sec2.2}
------------------------------------------------------------
siRNAs potentially may trigger off-target effects via several different mechanisms,[@bib37] such as the following: (1) the passenger strand of the siRNA mediates gene silencing in a complete-match manner (siRNA's working pattern); (2) either the passenger or guide strand of the siRNA mediates gene silencing via seed region matching (a microRNA \[miRNA\]-like pathway); and (3) gene disturbance resulting from an immune response stimulated by the siRNA molecule. Evaluation of on-target and off-target effects is of great importance for siRNA therapeutics development,[@bib38] since off-target effects may trigger serious toxicity *in vivo*.[@bib39]
psiCHECK, a more sensitive activity evaluation system than siQuant, was applied to determine the tiniest change in gene silencing. Meanwhile, CALAA-01 is an siRNA therapeutic that has been clinically studied in phase I for the treatment of solid tumor.[@bib28] The siRNA against RRM2 used in this clinical study was included as a control in this assay. GS-CM or PS-CM indicates the guide strand (GS) or passenger strand (PS) of the siRNA match with its targeting mRNA in a complete-match (CM) manner. The GS is the desired gene-silencing modulator, representing siRNA's on-target activity. GS-SM or PS-SM mean the guide or PS of the siRNA works via seed region matching, an miRNA-like pathway. Hence, gene silencing mediated by PS-CM, GS-SM, or PS-SM all represent siRNA's off-target effects. Data showed that the on-target IC~50~ of siRNA-04M in the HEK293A cell was 0.0078 nM, comparable with the IC~50~ of CALAA-01 (0.0035 nM) ([Figure 2](#fig2){ref-type="fig"}). No silencing activity was observed for all other three forms for siRNA-04M. However, significant off-target gene knockdown was observed for CALAA-01, as the IC~50~ values of PS-CM and GS-SM were 0.0724 and 1.0826 nM, respectively ([Figure 2](#fig2){ref-type="fig"}). Therefore, siRNA-04M is superior to CALAA-01 in terms of their on-target and off-target effects, supporting the following experiments with siRNA-04M both *in vitro* and *in vivo*.Figure 2On-Target Activity and Off-Target Effect of siRNA-04M and siRNA Contained in CALAA-01siRNA that works by its guide strand (GS) and completely matching (CM) with its targeting mRNA represents on-target activity (A and E). If it works by its passenger strand (PS) completely matching (CM) with its targeting mRNA (B and F), or either its GS or its PS matching with its targeting mRNA in the seed region (SM, seed match) (C, D, G, and H), an off-target effect may be generated. IC~50~ was calculated with GraphPad Prism 5 software and is shown in the upper-right corner. Data were shown as mean ± SD. Data were duplicated three times.
Toxicity Evaluation of siRNA {#sec2.3}
----------------------------
Cytotoxicity of the siRNA was further evaluated in PANC-1 cells with a 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Free uptake of the siRNA was applied at the concentrations of 0.4, 2, 10, 50, 250, 500, and 1,000 nM. Cell viability was well maintained for all treatment concentrations, suggesting good biocompatibility of siRNA-04M ([Figure S2](#mmc1){ref-type="supplementary-material"}).
In addition, *in vivo* toxicity, including cytokine inducement, of siRNA-04M was thoroughly investigated. Lipopolysaccharide (LPS) was included as a positive control. siRNA and LPS were all dosed at 5 mg/kg, via intravenous and intraperitoneal injection, respectively. Data revealed that LPS triggered significant cytokine release *in vivo*. The concentration of TNF-α (tumor necrosis factor alpha), IFN-γ (interferon gamma), IL-6 (interleukin-6), KC (keratinocyte-derived cytokine, or CXCL1 \[chemokine (C-X-C motif) ligand 1\]), MCP-1 (monocyte chemoattractant protein-1, or CCL2 \[chemokine (C-C motif) ligand 2\]), GM-CSF (granulocyte-macrophage colony-stimulating factor, or CSF2 \[colony-stimulating factor 2\]), and IL-12p70 were all dramatically increased in circulation. The ratios of spleen to body weight were also elevated significantly at 24 and 48 hr post-treatment. However, siRNA-04M did not induce any cytokine release, influence liver and kidney function, and had no impact on organ coefficients ([Figures S3--S5](#mmc1){ref-type="supplementary-material"}). Furthermore, the siRNA was dosed at a higher dose of 10 mg/kg via intravenous (i.v.) injection in another test. Concentrations of cytokines (IL-6 and TNF-α) and several biochemistry parameters (ALT \[alanine transaminase\], AST \[aspartate aminotransferase\], TP \[total protein\], and LDH \[lactate dehydrogenase\]) were recorded at 24 hr post-treatment ([Figure S6](#mmc1){ref-type="supplementary-material"}). It was also proven that the siRNA was well tolerated by animals, although a higher dose of siRNA has been applied.
In consideration, siRRM-04M with high potency, good stability, no off-target effect, and no toxicity was finally selected as the lead compound in this study. siRNA-04M is termed siRRM2 and used in the following experiments.
Influence of RRM2 Knockdown on Colony Formation {#sec2.4}
-----------------------------------------------
Colony formation assay was performed to evaluate the efficacy of RRM2 knockdown. siNC (a scramble siRNA without any targeting gene in mouse, rat, monkey, and human beings) was used as a control. Data revealed that the cells treated with siRRM2 showed a remarkable reduction of colonies compared with the cells treated with siNC ([Figure 3](#fig3){ref-type="fig"}A), suggesting RRM2 knockdown significantly influenced cell proliferation. The quantitative analysis data proved that the colonies decreased approximately 70% after treatment with siRRM2 ([Figure 3](#fig3){ref-type="fig"}B).Figure 3Cell Colonies of PANC-1 Cells Treated with siNC or siRRM2 at 50 nM(A) The digital images of cell colonies. (B) Quantification analysis of the colonies. Data were shown as mean ± SD. \*\*\*p \< 0.001, n = 3. The inserted percentages represent the relative colony numbers for these two treatments. The colony number of the cells treated with siNC was set as 100%, by normalizing to which, the relative colony number of cells treated with siRRM2 was calculated.
Cell-Cycle Arrest Induced by Knockdown of RRM2 {#sec2.5}
----------------------------------------------
To explore the mechanism of siRRM2's influence on cell proliferation, cell-cycle arrest assay was performed. Here, two classical antineoplastic drugs, cisplatin (Pt) and DOX, were used as positive controls at the doses of 25 and 0.2 μg/mL, respectively. The transfection concentrations of siRRM2 were 20 and 50 nM. Here, siNC (50 nM) was also included as negative control. Data manifested that both Pt and DOX induced significant G2/M checkpoint arrest ([Figures 4](#fig4){ref-type="fig"}B and 4C). Pt is an inorganic platinum complex, which induces cytotoxicity by inhibiting DNA synthesis by conforming DNA adducts. These DNA adducts can activate several signal transduction pathways, including Erk, p53, p73, and MAPK, which culminates in the activation of apoptosis.[@bib40], [@bib41] As a result, it will induce G2 arrest.[@bib41] Doxorubicin, an antibiotic anthracycline, is commonly considered to exert its anti-tumor activity at two fundamental levels, altering DNA and producing free radicals to trigger apoptosis of cancer cells through DNA damage. Doxorubicin-induced G2/M checkpoint arrest is attributed to elevated cyclin G2 (CycG2) expression and phospho-modification of proteins in the ataxia telangiectasia mutated (ATM) and ATM and Rad3-related (ATR) signaling pathways.[@bib42], [@bib43], [@bib44] In addition, compared with the controls of no treatment and siNC 50 nM, cells treated with siRRM2 (50 and 25 nM) displayed a remarkable and dose-dependent increase in S-phase populations; and the G2/M-phase population decreased significantly ([Figures 4](#fig4){ref-type="fig"}E and 4F). This was consistent with the S-phase cell-cycle arrest matched with the mechanism of action, and it was in line with the reported data.[@bib31], [@bib45] Synthesis of RRM2 protein is regulated in a cell-cycle-dependent fashion. It begins to rise in late G1 and reach the highest level during S-phase when DNA replication occurs. Therefore, when RRM2 expression is repressed by siRNA, the protein level will decrease in G1/S phase, resulting in the block of conversion of ribonucleoside 5′-diphosphates into their corresponding 2′-deoxyribonucleotides and the inhibition of DNA synthesis and replication.Figure 4Cell-Cycle Arrest Induced by Cisplatin, Doxorubicin, and siRRM2(A--F) The cell cycle distribution of untreated cells (A) and cells treated with cisplatin (B), doxorubicin (C), siNC at 50 nM (D), siRRM2 at 25 nM (E), and siRRM2 at 50 nM (F). (G) Percentages of cell populations in G1, G2, and S phases of the cells shown in (A)--(F). Data were shown as mean ± SD. n = 1 for cells treated with cisplatin and doxorubicin; n = 2 for untreated cells and the cells treated with siNC and siRRM2.
Impact of siRRM2 Transfection on Cell Morphology {#sec2.6}
------------------------------------------------
siRRM2 and DOX were further used to explore their influence on cell morphology. Data displayed that all three kinds of treatment induced remarkable cell shrinkage and death ([Figures 5](#fig5){ref-type="fig"}B--5D). Compared with untreated cells, cell numbers for the cells treated with DOX and/or siRRM2 were significantly reduced. Moreover, cells treated with DOX (0.2 μg/mL) and siNC (50 nM) showed a little bit better cell morphology than cells treated with siRRM2 alone (50 nM) and cells treated with siRRM2 combined with DOX. Combination treatment of siRRM2 and DOX caused almost all cells' death, suggesting a promising synergistic effect of siRRM2 and DOX on anti-proliferation activity.Figure 5Cell Morphology of Cells with Various Treatments(A--D) Cells without treatment (A), cells treated with DOX plus siNC (B), cells treated with siRRM2 alone (C), and cells treated with DOX plus siRRM2 (D).
Cell Viability for the Cells Treated with siRRM2 Alone or Combined with DOX {#sec2.7}
---------------------------------------------------------------------------
MTT assay was performed to evaluate the capability of siRRM2 in inhibiting tumor cell proliferation. First, DOX was applied to PANC-1 at 0.0, 0.1, 0.2, 0.4, 0.8, 1.6, 3.2, 6.4, and 12.8 ng/μL. Cell growth was repressed dose dependently compared with the cells without treatment. Cells treated with 0.1 and 3.2 ng/μL DOX exhibited ∼32% and ∼93% inhibition of cell viability, respectively. More than 90% inhibition efficiency was achieved when DOX was applied at \>1.6 ng/μL ([Figure 6](#fig6){ref-type="fig"}A). It was worthy to note that viabilities of the cells treated at doses of 6.4 and 12.8 ng/μL were comparable with those of the cells treated at doses of 1.6 and 3.2 ng/μL. That is because DOX itself can be excited at ∼545 nm, although the highest excitation wavelength for DOX is around 480 nm. The more DOX that is added into the cells, the stronger the signal interference that is observed.Figure 6Cell Viability of PANC-1 Cells Evaluated with MTT Assay(A) Cell viability of PANC-1 cells treated with DOX alone at various concentrations. Inserted graph shows the fitting curve of the cell viability, by which the IC~50~ was calculated. The data marked with a circle means that the data point is generated by reasonable assumption. (B) Cell viability of PANC-1 treated with siRRM2 alone or combined with DOX. Data were shown as mean ± SD. \*\*p \< 0.01, \*\*\*p \< 0.001, n = 6 (A) or 5 (B).
According to the result calculated by a fitting function of cell viability, the IC~50~ of DOX was ∼0.18 ng/μL ([Figure 5](#fig5){ref-type="fig"}A, inserted graph). The fitting curve was generated with GraphPad Prism software according to the formula of Y = Bottom + (Top − Bottom)/(1 + 10ˆ((X − LogIC~50~))). Moreover, cells treated with 0.1 ng/μL DOX (the lowest concentration we applied) remained at ∼70% cell viability. Since it did not reach the upper limit of cell viability, fitting function could not be generated in a reasonable way. Untreated cells were equal to 0.0 ng/μL DOX being added. However, a concentration of 0.0 ng/μL cannot be transferred to a Log value for plotting on the fitting function. Alternatively, to obtain an accurate IC~50~, we assumed that the cells treated with 0.005 ng/μL (an extremely low concentration) DOX displayed ∼100% cell viability (as marked with circle in the inserted graph). As a result, a well-fitting curve with an R^2^ (coefficient of determination) of ∼0.95 was generated, and the IC~50~ was successfully produced.
Second, siRRM2 was applied to cells alone or synergistically with DOX ([Figure 6](#fig6){ref-type="fig"}B). When siRRM2 was added alone to PANC-1 cells at 50 and 10 nM (transfection concentration), 35% and 30% growth inhibition were achieved, respectively. When siRRM2 (50, 10, and 2 nM) was co-added into the cells with 0.2 ng/μL DOX, they caused 75%, 66%, and 59% losses of cell viability, respectively. In addition, if the DOX concentration was reduced to 0.1 ng/μL, siRRM2 transfected at 50 and 10 nM still resulted in 64% and 56% losses of cell viability, respectively. Moreover, if we fixed the siRNA transfection concentration at 50 nM, applying 0.2 and 0.1 ng/μL DOX enhanced the inhibition efficiency from 35% (without DOX treatment) to 75% and 64%, respectively. When the concentration of siRRM2 was reduced to 10 nM, applying 0.2 and 0.1 ng/μL DOX elevated the inhibition efficiency from 30% (without DOX treatment) to 66% and 56%, respectively. Therefore, the combined use of the siRNA and DOX could achieve approximately two times higher efficacy than use of the siRNA alone. On the other hand, when siRRM2 was applied at 50 nM, 0.2 or 0.1 ng/μL DOX could induce 75% or 64% of cells to lose their viability, while 0.8 or 0.4 ng/μL DOX was needed if we wanted to achieve the same efficacy by DOX alone. This demonstrated that combination application of siRRM2 and DOX improved the efficacy by ∼4 times more than using DOX alone. Overall, cell viability data revealed a strong synergistic effect of siRRM2 and DOX on inhibiting the proliferation of PANC-1 cells ([Figure 6](#fig6){ref-type="fig"}B).
*In Vivo* Tumor Growth Inhibition {#sec2.8}
---------------------------------
To explore the potential of combination treatment of siRRM2 and DOX in pancreatic cancer therapy, tumor growth suppression was evaluated with PANC-1 tumor-bearing BALB/c nude mice. Mice were randomly divided into five groups when tumor volumes reached ∼50 mm^3^. Then the following formulations were administered twice weekly into the mice: group 1, normal saline; group 2, DOX (1.0 mg/kg) alone; group 3, DOX (1.0 mg/kg) combined with lipid nanoparticle (LNP)/siNC (5 μg/tumor); group 4, DOX (1.0 mg/kg) combined with LNP/siRRM2 (2 μg/tumor); and group 5, DOX (1.0 mg/kg) combined with LNP/siRRM2 (5 μg/tumor). DOX and LNP/siRNA complexes were administered via intraperitoneal (i.p.) and peritumoral injections, respectively. LNP used in this assay is a novel lipid-based delivery system that has exhibited excellent siRNA delivery efficacy *in vivo* (data not shown).
Data revealed that DOX alone could slightly suppress tumor growth and the combination of siRRM2 and DOX remarkably enhanced the inhibition efficiency of tumor growth ([Figure 7](#fig7){ref-type="fig"}A). For tumor volumes at day 19, p values of group 5 versus group 1, and group 5 versus group 3 were 0.019 and 0.007, respectively ([Figure 7](#fig7){ref-type="fig"}B). The tumor volumes of groups 4 and 5 at day 25 were significantly smaller than groups 1 and 3, as all four p values were less than 0.05 ([Figures 7](#fig7){ref-type="fig"}A and 7B).Figure 7Tumor Growth Inhibitions by DOX Alone or Combined with siRRM2 in PANC-1 Xenograft Tumor Murine Model(A) Tumor growth curves for five group mice with various treatments. (B) Statistical analysis results for the tumor volumes at days 19, 22, and 25. (C) Treatment information for these five groups of mice. (D and E) Digital pictures of the whole bodies of the mice (D) and the isolated tumor tissues (E) at the end time point (day 25). Scale bar, 2 cm. (F) Average tumor weights for five groups of mice at the end time point. The inserted percentages in the histograms represent the relative tumor weight by normalizing to the average tumor weight of group 1 that was treated with 1× PBS. (G) Body weights of the mice during the whole treatment course. (H) Organ coefficients of the liver and the spleen at the end time point. Data were shown as mean ± SEM. \*p \< 0.05, n = 8.
Digital pictures of whole bodies and isolated tumors also provided similar information ([Figures 7](#fig7){ref-type="fig"}D and 7E). More importantly, tumor weights recorded at the end time point demonstrated that tumor suppression efficiencies of groups 2--5, compared to group 1, reached ∼13%, ∼10%, ∼32%, and ∼43%, respectively ([Figure 7](#fig7){ref-type="fig"}F). The differences between group 5 and group 1, group 5 and group 3, as well as group 4 and group 3 were all significant. These data revealed that (1) DOX alone could inhibit pancreatic tumor growth to an extent; (2) the combination treatment of DOX and siRRM2 dramatically improved the suppression efficiency compared to applying DOX alone; (3) the synergistic effect was attributed to siRRM2, because DOX combined with siNC exhibited a comparable tumor inhibition as with DOX alone, and because the dose-dependent effect for the siRRM2 was clearly observed in this assay. In addition, body weight, organ coefficients (the ratio of liver and body weight and the ratio of spleen and body weight) proved that all treatments did not cause obvious adverse effects during the whole treatment course ([Figures 7](#fig7){ref-type="fig"}G and 7H). Clinical observation was also performed during the treatment course, and no abnormal behavior was observed.
Discussion {#sec3}
==========
Pancreatic cancer is a cancer type with a high degree of malignancy. It will become the second leading cause of cancer-related death by 2030 in the United States. DOX is an anthracycline antibiotic and a first-line anti-neoplastic drug for the treatment of a wide variety of cancers. RRM2, a pivotal gene involved in carcinogenesis, is a new molecular marker for the diagnosis and clinical outcomes of cancer, and a potential therapeutic target as well. LNP is a powerful and well-studied siRNA delivery system. LNP used in this study is a novel lipid-based nucleic acid delivery system, and previously it has been demonstrated to be a potent siRNA transporting tool with an ED~50~ of ∼0.05 mg/kg when used for liver-targeting delivery. On the other hand, the combination of several different anti-tumor reagents has become an effective and feasible treatment method for pancreatic cancer.[@bib46], [@bib47], [@bib48], [@bib49] In this study, DOX and LNP-loaded siRRM2 were combinedly given to tumor-bearing mice. Tumor growth was significantly inhibited with this combination strategy. A strong synergistic effect has been observed and achieved, as applying the siRNA reduced the required dose of DOX while achieving the same efficacy as when applying DOX alone, and, in turn, DOX also enhanced the anti-tumor effect of the siRNA ([Figures 6](#fig6){ref-type="fig"} and [7](#fig7){ref-type="fig"}).
In conclusion, in this study we designed 23 siRNAs against RRM2, a pivotal gene involved in DNA synthesis and replication, and one of them was selected as the lead sequence. It was observed that both siRRM2 alone and DOX alone could induce significant cell growth inhibition, as suggested by the data of cell colony formation, cell-cycle arrest, cell morphology, and cell viability. Combined application of siRRM2 and DOX dramatically enhanced the anti-tumor efficacy by ∼4 times more than applying DOX alone. Moreover, a tumor growth inhibition assay performed in a PANC-1 xenograft tumor model demonstrated that the combination of siRRM2 and DOX significantly suppressed the tumor growth *in vivo*. The inhibition efficiency revealed by tumor weight at the endpoint reached \>40%. Therefore, this work offers a good siRNA molecule against RRM2. This siRNA significantly inhibited the growth of pancreatic cancer cells *in vitro* and *in vivo*, regardless of applying it alone or in combination with DOX. The regimen explored in this work constitutes a safe and feasible salvage therapy in patients with pancreatic cancer, exhibiting good potential for clinical translation in the future.
Materials and Methods {#sec4}
=====================
Materials {#sec4.1}
---------
siNC (catalog: SR-NC001, without any targeting gene in mouse, rat, and human) and siRRM2 (catalog: SR3204M, targeting ribonucleotide reductase M2 \[RRM2\]), were synthesized by Suzhou Ribo Life Science (Kunshan, China). To enhance their stability, several bases of their sequences were modified with methoxy group or fluorine at the 2′ site hydroxyl groups. Lipofectamine 2000, DMEM, Opti-MEM, fetal bovine serum (FBS), penicillin, streptomycin, trypsin, and TRIzol were purchased from Life Technologies (Molecular Probes, Eugene, OR, USA). Cell culture plates and serological pipettes were from Corning (NY, USA). Reverse transcription kit and real-time PCR kit (UltraSYBR Mixture) were purchased from Promega (Fitchburg, WI, USA) and Beijing ComWin Biotech (Beijing, China), respectively. Golden View used for staining nucleic acid in gel was purchased from Beijing BioDee BioTech (Beijing, China). Loading buffer was provided by Takara Bio (Japan). Agrose was from Oxoid (UK, part of Thermo Fisher Scientific). Crystal Violet Staining Solution was purchased from Beyotime Biotechnology (Haimen, Jiangsu, China). RNA*later*, doxorubicin, Pt, and propidine iodide (PI) were purchased from Sigma-Aldrich (St. Louis, MO, USA). PI is a popular red fluorescent nuclear and chromosome counterstain. RNase A was provided by TransGen Biotech (Beijing, China). Pentobarbital sodium was provided by Peking University Laboratory Animal Center.
Cell Culture {#sec4.2}
------------
PANC-1, a pancreatic carcinoma cell line, was obtained from the Cell Resource Center of Peking Union Medical College (Beijing, China). HEK293A, a human embryonic kidney cell line, was kept in our lab. Both cells were cultured with DMEM supplemented with 10% FBS, 100 U/mL penicillin, and 100 μg/mL streptomycin at 37°C in a humidified atmosphere of 5% CO~2~.
Activity Screening of siRNAs with siQuant or psiCHECK Assay {#sec4.3}
-----------------------------------------------------------
siRNAs targeting RRM2 were designed by scientists from Suzhou Ribo Life Science and screened with the siQuant system, a previously reported and well-defined siRNA validation method.[@bib35] Briefly, human embryonic kidney cells (HEK293A) were grown in DMEM supplemented with 10% FBS, 100 U/mL penicillin, and 100 μg/mL streptomycin. The cells were seeded into 24-well plates at a density of ∼5 × 10^4^ cells/well 1 day before transfection. Reporter plasmid (firefly luciferase expression plasmid, 100 ng/well) carrying siRNA target was transfected into the cells at approximately 60% confluence using lipofectamine 2000 (1 μL/well), together with pRL-TK control vector (renilla luciferase expression plasmid, 50 ng/well), also with siRNA against RRM2 or scramble siRNA (negative control \[NC\]) or positive control siRNA (positive control \[PC\]). The transfection concentration of siRNA against RRM2 was 1, 0.1, or 0.05 nM. 24 hr after transfection, the activities of both luciferases were determined by a fluorometer (Synergy HT, BioTek Instruments, Winooski, VT, USA). The firefly luciferase signal was normalized to the renilla luciferase signal for each individual well, and the silencing efficacy of each siRNA was calculated by comparison with the sample treated with NC siRNA. All experiments were performed in triplicates and repeated at least twice.
For the on-target and off-target evaluation of siRNAs, psiCHECK dual-luciferase reporter system (Promega, Madison, WI, USA),[@bib50] a more sensitive reporter system than siQuant, was applied. Both firefly and renilla luciferase expression sequences were constructed in one plasmid. The target of siRNA was inserted into the psiCHECK-2 plasmid at the 3′ UTR of renilla luciferase. siRNA was transfected into HEK293A at a series of transfection concentrations of 1.0000, 0.5000, 0.2500, 0.1250, 0.0625, 0.0313, 0.0156, 0.0078, 0.0039, 0.0020, and 0.0010 nM. The activity of both luciferases was determined 24 hr after transfection by a Synergy HT fluorometer. Cells were lysed with Passive Lysis Buffer (Promega). Firefly and renilla luciferase activities were evaluated with the Dual-Luciferase Reporter Assay system (Promega). Renilla luciferase activity was normalized to the firefly luciferase activity, in contrast to the siQuant system. Then siRNA activity was calculated by comparison with the NC sample. Then the fitting curve was generated; the IC~50~ was calculated with GraphPad Prism 5.0 software.
Validation of the siRNA's Activity in PANC-1 with RT-PCR {#sec4.4}
--------------------------------------------------------
To validate the silencing efficiency of siRNAs targeting RRM2, qRT-PCR was performed in PANC-1. Cells were plated in 12-well plates (1 × 10^5^ per well) 1 day before transfection and incubated in DMEM to approximately 60% confluence. Then siRNAs were transfected into the cells with lipofectamine 2000 at the concentrations of 20 and 50 nM. 24 hr later, total RNA of the cells was harvested with Trizol according to the manufacturer's protocol. Then, cDNA was prepared by two-step reverse transcription. First, 1 μg total RNA was incubated for 10 min at 70°C, followed by immediately transferring onto ice. Then 2 μL 10× reaction buffer; 4 μL MgCl~2~ (25 mM); 2 μL dNTP (10 mM); 0.5 μL RNase inhibitor; and 1 μL (15 U) AMV reverse transcription enzyme, 1 μL oligo dT, and the desired volume of ddH~2~O were added into the precooled tube (20 μL in total), followed by a reaction at 42°C for 30 min and 95°C for 5 min, respectively. Then the cDNA solution was diluted 5 times by adding 80 μL ddH~2~O. A real-time PCR reaction system (10 μL 2× UltraSYBR Mixture, 0.5 μL forward primer \[10 μM\], 0.5 μL reverse primer \[10 μM\], 5 μL cDNA solution, and 4 μL ddH~2~O) was prepared and first hot-started for 10 min at 95°C before 40 cycles of 30 s at 95°C, 30 s at 59°C, and 30 s at 72°C. After the melting procedure was completed, the samples were stored at 4°C. The expression level of RRM2 was analyzed by the Ct (cycle threshold) values using standard protocol.
Colony Formation Assay {#sec4.5}
----------------------
Colony formation assay was employed to evaluate the influence of siRRM2 on the proliferation of PANC-1. PANC-1 cells were plated in 6-well plates (300 cells/well in 2 mL DMEM) 1 day before transfection. siRRM2 and irrelevant siRNA (siNC) were added into each well at the transfection concentration of 50 nM. Triplicates were used in this assay. After incubation at 37°C for 4 hr, 4 mL fresh DMEM containing 10% FBS was added. Then the medium was replaced once every 3 days with 4 mL fresh DMEM containing 10% FBS, 100 U/mL penicillin, and 100 μg/mL streptomycin. 10 days after transfection, the colonies were washed twice with 1× PBS, followed by fixing and staining for 30 min with a solution containing 0.1% (w/v) crystal violet and 20% (v/v) ethanol. Then the colonies were washed again to remove excess crystal violet with 1× PBS. Finally, after the dishes were dry, digital images of the colonies were acquired using a camera, and colony numbers were counted.
FACS Assay for Cell-Cycle Arrest {#sec4.6}
--------------------------------
Fluorescence-activated cell sorting (FACS) was used to examine the cell cycle of the cells treated with various formulations. PANC-1 cells were plated in 6-well plates (2 × 10^5^ per well) 1 day before transfection, and they were cultured in DMEM supplemented with 10% FBS, 100 U/mL penicillin, and 100 mg/mL streptomycin to 60%--70% confluence. After replacing DMEM with Opti-MEM, a reduced serum medium, siRRM2 (25 or 50 nM) and irrelevant siRNA (siNC, 50 nM) were transfected into each well at the desired concentrations with lipofectamine 2000. DOX and Pt were included as positive controls. The transfection concentrations of doxorubicin and Pt were 0.2 and 25 μg/mL, respectively. After incubation at 37°C for 4 hr, 2 mL fresh DMEM containing 10% FBS was added, followed by further incubation for 68 hr. Then the cells were washed once with ice-cold 1× PBS and re-suspended in 0.5 mL 1× PBS. Then 3.0 mL 70% cold EtOH was added into the cells, followed by fixing the cells at −20°C for 3 hr. Subsequently, the cells were centrifuged at 2,000 rpm/min for 5 min and washed once with 5 mL 1× PBS containing 1% FBS (50 μL). Then the cells were centrifuged at 2,000 rpm/min for 5 min and re-suspended in 200 μL PBS and 6 μL RNase (20 mg/mL), and 20 μL of a solution containing 500 μg/mL PI and 10% Triton X-100 was added. The mixture was gently blended, kept in a dark place, and incubated at 37°C for 30 min. Finally, the cells were centrifuged at 2,000 rpm/min for 5 min, and the precipitates were re-suspended in 600 μL PBS before proceeding to FACS assay. The cell cycle profiles were analyzed using a BD Biosciences FACScan (Becton Dickinson, San Jose, CA, USA) with MODFIT software. At least 10,000 cells in each sample were analyzed to obtain a measurable signal. All measurements were performed using the same instrument setting.
Influence of siRRM2 on Cellular Morphology {#sec4.7}
------------------------------------------
To investigate the influence of siRNA targeting RRM2 (siRRM2) on the cellular morphology of PANC-1, cells were planted in 6-well plates (2 × 10^5^ per well) 1 day before transfection. siRRM2 was transfected into the cell with lipofectamine 2000 at the concentration of 50 nM. Doxorubicin (0.2 μg/mL) and Pt (25 μg/mL) were used as positive controls. In addition, cells treated with doxorubicin (0.2 μg/mL) combined with siRRM2 (50 nM) or siNC (50 nM) were included as an additional group. 72 hr later, the cells were observed using an inverted fluorescence microscope (Olympus X71, Olympus, Tokyo, Japan), and digital images were acquired and analyzed with the software package provided by Olympus.
MTT Assay {#sec4.8}
---------
An MTT assay was employed to evaluate the synergistic effect of siRRM2 and DOX in PACN-1 cells. The cells were seeded at 4,000 cells/100 μL DMEM/well on a 96-well plate, and they were allowed to adhere overnight at 37°C. First, we explored the anti-proliferation efficacy of treatment with DOX alone. The concentrations of DOX were 0.0, 0.1, 0.2, 0.4, 0.8, 1.6, and 3.2 ng/μL, respectively. Second, we evaluated the synergistic effect of combination treatment with siRRM2 and DOX. Here, the concentration of DOX was fixed at 0.2 ng/μL for panel 1; siRRM2 was co-transfected at 50, 10, and 2 nM, respectively. DOX alone (0.2 ng/μL) and DOX (0.2 ng/μL) plus siNC (50 nM) were included as controls. For panel 2, DOX was fixed at 0.1 ng/μL; siRRM2 was co-added into the cells at 50 and 10 nM, respectively. Meanwhile, cells treated with siRRM2 alone (50 and 10 nM) were also explored. 4 hr after transfection, 200 μL fresh complete DMEM was added. 68 hr after transfection, 200 μL medium was removed, and 10 μL MTT (5 mg/mL) was added into each well, followed by another incubation of 4 hr under the same incubator conditions. Then, the entire medium was removed and 150 μL DMSO was added and incubated for 10 min at 37°C to dissolve formazan. Finally, the absorbance was read at 545 nm, and the absolute absorbance (OD~net545~) was generated as OD~545~ − OD~545woc~. OD~545woc~ represents the average value of OD~545~ collected from six wells with the same solutions to the experimental plates but without any cells.
To compare the relative viability, all the data were presented as the mean percentage ± SD of six or five replicates compared with the value of mock-treated cells. The cell viability was calculated as follows: cell viability (%) = (OD~545(sample)~/OD~545(control)~) × 100, where OD~545(sample)~ is the absorbance at 545 nm of the transfected cells and OD~545(control)~ is the absorbance at 545 nm of the mock control (nontransfected cells). IC~50~ (the half maximal inhibitory concentration) of DOX was calculated according to a fitting curve of cell viability. The fitting curve was generated with GraphPad Prism software according to the function of Y = Bottom + (Top − Bottom)/(1 + 10ˆ((X − LogIC~50~))), whose R^2^ (coefficient of determination) was ∼0.95.
In addition, MTT was also employed to evaluate the cytotoxicity of naked siRNA. Here, siRNA was applied to the cell at the concentrations of 1,000, 500, 250, 50, 10, 2, and 0.4 nM, respectively, without transfection reagent. Cell viability was determined at 24 hr post-treatment according to the above-mentioned protocol.
Tumor Growth Suppression *In Vivo* {#sec4.9}
----------------------------------
Animals were purchased from Vital River Laboratory Animal Technology and maintained in Peking University Laboratory Animal Center (an AAALAC-accredited and specific-pathogen-free \[SPF\] experimental animal facility). All procedures involving experimental animals were performed in accordance with protocols approved by the Institutional Animal Care and Use Committee (IACUC) of Peking University.
Male BALB/c nude mice, 6--8 weeks old and weighing 18--22 g, were used to evaluate the anti-tumor effect of siRNA-loaded LNPs combined with DOX. First, 5 × 10^6^ PANC-1 cells (in 100 μL) were injected subcutaneously into the right axillary fossa of the mice. The tumor volume was monitored by measuring the perpendicular diameter of the tumor using calipers, and it was calculated according to the following formula: tumor volume (mm^3^) = 0.5 × length × width.[@bib2] When the volumes of the tumors had increased to ∼50 mm^3^, mice were randomly divided into five groups (eight mice per group), followed by administration of the following formulations, respectively: (1) normal saline, (2) DOX (1.0 mg/kg), (3) DOX (1.0 mg/kg) combined with LNP/siNC (5 μg/tumor), (4) DOX (1.0 mg/kg) combined with LNP/siRRM2 (2 μg/tumor), and (5) DOX (1.0 mg/kg) combined with LNP/siRRM2 (5 μg/tumor). DOX and LNP/siRNA complexes were administered twice weekly via i.p. and peritumoral injections, respectively. 25 days later, mice were sacrificed by cervical dislocation, the tumors were isolated, and the digital images were acquired. The weights of tumor, liver, and spleen were also recorded.
The LNP/siRNA complex was prepared by Suzhou Ribo Life Science (Kunshan, China). The proposed LNP is a novel lipid-based breakthrough reagent for *in vivo* RNAi delivery, with greatly improved performance and up to 85% knockdown achieved using microgram levels of siRNA (data not shown; Y.H., unpublished data). It is composed of a proprietary ionizable amino lipid, PEGylated lipid, and cholesterol. The average particle size of LNP/siRNA, as determined by dynamic light scattering (ZEN3500, Malvern Instruments, UK), was approximately 80 nm. Encapsulation efficiency was calculated by determining unencapsulated siRNA content by measuring the fluorescence upon the addition of RiboGreen (Molecular Probes, Eugene, OR) to the LNP slurry (Fi) and comparing this value to the total siRNA content obtained upon lysis of the LNPs by 1% Triton X-100 (Ft), where percentage encapsulation = (Ft − Fi)/Ft × 100. As a result, the encapsulation efficiency of LNP/siRNA was higher than 90%.
Statistical Analysis {#sec4.10}
--------------------
The data were expressed as the mean ± SD or mean ± SEM, as indicated in the figure legends. The statistical variance was calculated by a t test; p \< 0.05 was considered statistically significant.
Author Contributions {#sec5}
====================
Y.H., X.J., and S.G. designed and led the research. Y.H., X.J., S.Z., X.W., Y.-H.W., J.-L.J., L.G., B.H., N.L., H.B., J.Z., and T.Y. performed the research. L.G., S.Z., H.B., J.Z., and Q.C. were involved in the animal study. X.-H.X. was involved in discussion of the data and provided insightful suggestions. Y.H., X.J., S.G., and H.-Y.Z. analyzed the data. Y.H. summarized the data, prepared the figures, and wrote the paper. All authors discussed results and commented on the paper.
Conflicts of Interest {#sec6}
=====================
X.J., J.-L.J., L.G., B.H., N.L., J.Z., H.B., S.G., and H.-Y.Z. are employees of Suzhou Ribo Life Science Co. Ltd.
Supplemental Information {#appsec2}
========================
Document S1. Supplemental Materials and Methods and Figures S1--S6Document S2. Article plus Supplemental Information
This work was supported by the Beijing Institute of Technology Research Fund Program for Young Scholars and the Fundamental Research Funds for the Central Universities, the Hunan Provincial Natural Science Foundation of China (2018JJ1019), the Hu-Xiang Young Talent Program, the National Drug Program of China (2015ZX09102-023-002 and 2014ZX09304313-001), and the Jiangsu Provincial Natural Science Foundation of China (BK2011381). It was also financially supported by Suzhou Ribo Life Science Co. Ltd.
Supplemental Information includes Supplemental Materials and Methods and six figures and can be found with this article online at [https://doi.org/10.1016/j.omtn.2018.08.003](10.1016/j.omtn.2018.08.003){#intref0010}.
[^1]: These authors contributed equally to this work.
[^2]: Present address: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
|
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Q:
Laravel 5: Need to sort a grouped collection by an attribute of first item of each group
I have a collection of some Eloquent model items from my database which are grouped by an attribute using groupBy(), I need to sort that collection by another attribute of the first item of each group but preserve the initial structure. How can I achieve this, if possible at all?
A:
groupBy returns a collection, so you should still be able to use the sortBy method. You need to use a callback to get the attribute value from the first item in each group rather than just giving it a string.
$sorted = $groups->sortBy(function ($group, $key) {
return $group->first()->someAttribute;
});
|
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c# WPF bind combobox to TPH in Entity Framework code first using LINQ
I'm building a WPF application using entity framework code first for the database. I need to bind my combobox to a TPH table that has a discriminator for two types of entity.
I've tried to query like this in XAML.CS:
var pet = (from Pet in db.Pet.OfType<Dog>()
select Pet).ToList();
ComboBoxDog.ItemsSource = pet;
And my combobox in XAML
<ComboBox x:Name="ComboBoxDog" ItemsSource="{Binding Path = Name}" HorizontalAlignment="Left" Margin="203,81,0,0" VerticalAlignment="Top" Width="138" Height="28" SelectionChanged="cBoxServer_SelectionChanged"/>
If I remove Path=Name from combobox and .OfType<Server>() from my query it's showing values correctly, but without taking in considerations the discriminator. I would like to show only Name attribute.
A:
You need to set the DisplayMemberPath ,DisplayMemberPath specifies the path to the display string property for each item. In your case
<ComboBox x:Name="cBoxServer" ItemsSource="{Binding}" DisplayMemberPath="{Binding Name}" HorizontalAlignment="Left" Margin="203,81,0,0" VerticalAlignment="Top" Width="138" Height="28" SelectionChanged="cBoxServer_SelectionChanged"/>
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Empress Zhu (Song dynasty)
Empress Zhu (1102–1127), was a Chinese Empress consort of the Song Dynasty, married to Emperor Qinzong of Song.
Zhu was born in Bianjing in 1102. Zhu was married to Qinzong as his primary consort in 1116. In 1126, Emperor Huizong abdicated in favor of his son, Emperor Qinzong. Zhu, as his primary consort, was appointed to the position of empress.
In 1127, the capital of Bianjing was captured by the Jurchen during the Jin–Song Wars. The Emperor Qinzong was deposed, and him, as well as his predecessor Emperor Huizong and most of the Imperial family and court, over 3000 people, was captured and exiled to Manchuria in what was called the Jingkang Incident.
They were first taken to the Jurchen capital, many of them dying on the way. The Imperial consorts, concubines, palace women and eunuchs who were taken captured, were distributed among the Jurchen as slaves. Her father-in-law were allowed to keep five of his spouses, including his empress, because they were too old to be of interest as war prizes. Empress Zhu, however, was young and described as a beauty, and not expected to be allowed to remain with her spouse. Upon her arrival, she was ordered to take a bath. Humiliated, she committed suicide to avoid sexual abuse.
References
Notes
Works cited
Category:Song dynasty empresses
Category:1102 births
Category:1127 deaths
Category:Chinese royalty who committed suicide
Category:12th-century Chinese women
Category:12th-century Chinese people |
hurricane
Puerto Rico is trying to start the process of recovering from Hurricane Maria — and it's doing so after the powerful storm blew homes apart, filled roads with water and tore at its infrastructure. Flash floods are persisting, and the island has no electricity service.
"We are without power, the whole island is without power," Jenniffer González-Colón, Puerto Rico's resident commissioner — its representative in Congress — told Morning Edition on Thursday. González-Colón spoke from Carolina, near San Juan.
Even though Maria has weakened to a Category 4 storm, it remains a dangerous hurricane. Maria's maximum sustained winds are near 155 mph. The National Hurricane Center says the storm should keep that intensity until it makes landfall. Puerto Rico has long been spared from a direct hit by a hurricane.
Making landfall Saturday, Hurricane Matthew brought floods and strong winds to South Carolina's Lowcountry region, pouring rain into an area that now faces a dangerous storm surge. As of 11 a.m. ET, the storm's center was around 55 miles south-southwest of Myrtle Beach.
The eye of Hurricane Matthew is just off the coast of Georgia, pushing surge flooding into Florida and Georgia, according to the National Hurricane Center. The storm's highest sustained winds are 105 mph. The storm is expected to move near or over the coast of South Carolina Saturday.
Late Thursday night President Obama declared a state of emergency in 30 Georgia counties. The president's action authorizes FEMA to coordinate all disaster relief efforts and provide "appropriate assistance."
That's how Jacqueline Charles of the Miami Herald described the situation in Port-au-Prince, Haiti, in an interview with NPR Wednesday morning. "A lot of rain and a lot of wind," she said. "Before [Hurricane] Matthew, the ground was already saturated, so the idea that you could have 25 inches of rain is a very scary thought." |
[Establishment of a podocyte cell injury model induced by puromycin aminonucleoside].
To establish a podocyte cell injury model induced by puromycin aminonucleoside (PAN), an in vitro model for studying the role of podocytes, especial the slit diaphragm molecules in proteinuria at the cellular and molecular levels. MPC5 were treated for 24 and 48 hours by 15, 45 and 75 mg/L PAN, respectively. The podocyte molecular behavior during podocyte injury was evaluated: the apoptotic podocyte cells were revealed with FITC-Annexin V and Propidium Iodide (PI) assay and the proliferative podocyte cells detected with MTT assay after PAN treatment. The distribution of Nephrin and Podocin was revealed with indirect-immunofluorescent staining under confocal microscope. The distribution of F-actin was revealed with direct-immunofluorescent staining under microscope. The percentage of apoptotic podocyte cells was increased in a dose- and time-dependent manner after PAN treatment. In PAN-treated group, the apoptosis was obviously increased at hour 48, the PAN-45 treated group was 33.48% +/- 14.55% and PAN-75 treated group 38.01% +/- 12.13% vs the control group 6.38% +/- 0.50% (P<0.01). We set up an in vitro podocyte injury model treated with PAN for the first time. This reliable cell model is a good basis for further studies on podocyte injury. |
<?php
/**
* Copyright 2017 OpenCensus Authors
*
* Licensed under the Apache License, Version 2.0 (the "License");
* you may not use this file except in compliance with the License.
* You may obtain a copy of the License at
*
* http://www.apache.org/licenses/LICENSE-2.0
*
* Unless required by applicable law or agreed to in writing, software
* distributed under the License is distributed on an "AS IS" BASIS,
* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
* See the License for the specific language governing permissions and
* limitations under the License.
*/
namespace OpenCensus\Trace;
/**
* An abstract class that represents a TimeEvent resource.
*/
abstract class TimeEvent
{
use DateFormatTrait;
/**
* @var \DateTimeInterface The time of this event
*/
protected $time;
/**
* Create a new TimeEvent.
*
* @param array $options [optional] Configuration options.
*
* @type \DateTimeInterface|int|float $time The time of this event.
*/
public function __construct($options = [])
{
$options += [
'time' => null
];
$this->setTime($options['time']);
}
/**
* Return the time of this event.
*
* @return \DateTimeInterface
*/
public function time()
{
return $this->time;
}
/**
* Set the time for this event.
*
* @param \DateTimeInterface|int|float $time The time of this event.
*/
public function setTime($time = null)
{
$this->time = $this->formatDate($time);
}
}
|
The Quaker Connection
Did you go to church last Sunday? Now I don’t mean the Methodist or Baptist Churches, or the United Reformed or Catholic. I mean your local Church of England parish church! The chances are that you didn’t. As a minister in the United Reformed Church I certainly didn’t.
Of course it does not matter very much. Three hundred and thirty years ago it mattered a great deal. It was an offence not to attend your local parish church, and you could be fined for not doing so. And people like me who met in a religious assembly not approved by the state could find themselves in prison!
In the book A Collection of the sufferings of the People called Quakers by Besse there are details given of Quakers (members of the Religious Society of Friends) who were persecuted for being Quakers and who would have nothing at all to do with the church by law established in England. Some were fined, others had their possessions taken sequestrated and yet others ended up serving gaol terms of up to six months. Among the Quakers so persecuted was a certain John Linfield who appeared at the Sessions in Horsham in 1662 after being whisked out of a Quaker act of worship. He was “fined and sent to prison, whence after two months (he was) removed to the House of Correction, and detained three months longer.” Poor old John found himself back in court three years later. This time in Petworth. His crime? Not attending the parish church! In 1683 a certain William Linfield was accused of taking part in a riotous assembly. With one hundred others he had taken part in a Quaker act of worship, which to call a riotous assembly stretches human credulity beyound breaking point!
How many other Quaker Linfields were hounded by law enforcement officers? Alas we do not know. Others must have suffered because, by all acounts, there were quite a number of Quaker Linfields in the seventeenth and eighteenth centuries in central, northern Sussex. For one reason or another these Linfields moved out of the Society of Friends sometime during the eighteenth century. We can only but guess as to the reasons. One may have been because of “marrying out”, that is marrying a non-Quaker, which automatically brought with it expulsion from the Society. Another may have been “marrying before a priest”, an offence which also brought with it expulsion. Quakers marriages were not, strictly speaking, legal marriages for quite a time. These marriages were entered into in Meeting Houses, but were not recognised by the State. In consequence Quaker offspring were regarded as illegitimate and all manner of inheritance issues for such children were highlighted because of this. Whatever the reason Quakerism and the Linfields parted company sometime in the eighteenth century.
There appears to have been a strong connection between the Quaker Linfields and the Society meeting in Ifield in Crawley. John and Peter Linfield were two such people. Both must have met with William Penn, after whom the American state of Pennsylvania is named. He often attended the Ifield Meeting House and the table and chair there are supposed to have been given by him from his house at Warminghurst.
The above named John of Ifield was the son of William of Horsham. He went to live at Ifield and his name appeared in the account book of that Meeting for the first time in 1689. “He was a tenant of the Meeting, and … must have lived in the cottage at the Meeting House, his rent being paid regularly until 1727. The last Linfield entry was in 1729, the year of John’s death, when his son Josiah paid the year’s rent.”
Which brings us back to a parting of the ways between the Linfields and the Quakers. I wonder what the reason really was. |
Features & Benefits
Product Details
Part Number:
099-449
Weight:
6.0lbs
Universal or Direct Fit:
Direct fit
OEM Replacement:
Yes
Easy Installation:
Yes
Shipping Information:
Overnight and Two Day shipping are not available for PO Box, APO/FPO/DPO or US Territory addresses.This product may be shipped directly by the vendor to any eligible US addresses, excluding APO/FPO/DPO or US Territory addresses. |
Population dynamics of Culex quinquefasciatus and the fungal pathogen Lagenidium giganteum (Oomycetes: Lagenidiales) in stagnant water pools.
The fungal pathogen Lagenidium giganteum (California isolate), cultured on sunflower seed extract (SFE) and agar, was introduced once (May 15) into outdoor caged replicated stagnant water pools containing all instars of larval Culex quinquefasciatus. Subsequently, first-instar larvae were added daily (May 15-September 30) to simulate natural oviposition. The fungus persisted for the entire 138-day study period, which corresponded with the season of Cx. quinquefasciatus breeding in this region of North Carolina, and recycled in the mosquito larvae producing an 82% reduction of adult mosquitoes produced in comparison to untreated pools. The cycles of fungal activity varied among the pools with 2-4 major epizootics occurring during the study period. Data are presented on the cycling of populations of fungal zoospores, mosquito larvae, pupae and adults during the entire mosquito breeding season. |
Q:
Retrieve the Median from a decimal column using PERCENTILE_CONT SQL
I have a table Prices Like:
ID PurchasePriceCalc
0146301 0.002875161
00006L00 0.00396
00087G03 NULL
00001G04 0.0020004
00006S 0.003689818
01580h01 NULL
00082EE00 0.002462687
00038R05 0.002237565
01666R01 0.002666667
I Would like to get the Median per each PurchasePriceCalc and then subtract the result with the PurchasePriceCalc, for a better explanation the Formula should be : (PurchasePriceCalc - Median(PurchasePriceCalc)).
I'm using the query below but is not working:
SELECT ID,PurchasePriceCalc, PurchasePriceCalc - PERCENTILE_CONT(0.5) WITHIN GROUP (ORDER BY PurchasePriceCalc)
OVER (PARTITION BY ID) AS MediaCalc FROM Prices
This is how should be the Output, (Yellow Column).
Any assistance or help would be really appreciated!
A:
I guess the problem is with OVER (PARTITION BY ID). If ID is UNIQUE then each group consists of only one row that is why you get all values equal 0/NULL.
You should remove PARTITION BY part.
SELECT ID,PurchasePriceCalc,
PurchasePriceCalc - PERCENTILE_CONT(0.5)
WITHIN GROUP(ORDER BY PurchasePriceCalc) OVER () AS MediaCalc
FROM Prices;
|
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