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'' FreeBASIC binding for allegro-5.0.11 '' '' based on the C header files: '' Copyright (c) 2004-2011 the Allegro 5 Development Team '' '' This software is provided 'as-is', without any express or implied '' warranty. In no event will the authors be held liable for any damages '' arising from the use of this software. '' '' Permission is granted to anyone to use this software for any purpose, '' including commercial applications, and to alter it and redistribute it '' freely, subject to the following restrictions: '' '' 1. The origin of this software must not be misrepresented; you must not '' claim that you wrote the original software. If you use this software '' in a product, an acknowledgment in the product documentation would be '' appreciated but is not required. '' '' 2. Altered source versions must be plainly marked as such, and must not be '' misrepresented as being the original software. '' '' 3. This notice may not be removed or altered from any source '' distribution. '' '' translated to FreeBASIC by: '' Copyright © 2015 FreeBASIC development team #pragma once #ifdef __FB_UNIX__ #inclib "allegro_acodec" #elseif defined(__FB_WIN32__) and defined(ALLEGRO_STATICLINK) #inclib "allegro_acodec-5.0.10-static-md" #else #inclib "allegro_acodec-5.0.10-md" #endif #include once "allegro5/allegro.bi" #include once "allegro5/allegro_audio.bi" extern "C" #define __al_included_allegro5_allegro_acodec_h declare function al_init_acodec_addon() as byte declare function al_get_allegro_acodec_version() as ulong end extern
Meyaadha Maan Meyaadha Maan () is a 2017 Indian Tamil-language romantic comedy film written and directed by Rathna Kumar in his directorial debut. The film stars Vaibhav and Priya Bhavani Shankar, with Vivek Prasanna, Indhuja Ravichandran, Arun Prasath and Amrutha Srinivasan in supporting roles. Vivek Prasanna won the Vijay Award for Best Supporting Actor for his performance in the film. Karthik Subbaraj presented the film and Kaarthekeyen Santhanam produced the film through their production house, Stone Bench Creations. The film's original soundtrack and score were jointly composed by Santhosh Narayanan and Pradeep Kumar, with the latter making his composing debut in Tamil cinema. The film focuses on 'Idhayam' Murali, a happy-go-lucky light music singer, and his relationships with his longtime, one-sided love interest Madhumitha, his sister Sudarvizhi and his best friend Vinoth. Production was completed silently and the venture was first reported by the media during June 2017, with the film being shot primarily in Royapuram, Chennai. The film was released on 18 October 2017, coinciding with Diwali, and received positive critical reception. Plot Murali (Vaibhav), also known as 'Idhayam' Murali by his friends as he is like the emotional lead character from the film, Idhayam (1990), rings his friends, Vinoth (Vivek Prasanna) and Kishore (Arun Prasath) informing them that he is going to commit suicide, as he is not able to bear the engagement of his college mate, Madhu (Priya Bhavani Shankar), whom Murali has feelings of one-sided love. In an attempt to stop his suicide, Vinoth and Kishore request Madhu to speak badly about Murali, which Madhu does hesitantly. On hearing this, Murali feels outraged and cancels his suicide attempt. He also believes that Madhu is a bad girl. However, he blabbers about Madhu and how he loved her which slightly moves Madhu. The marriage is postponed by a year. One year later, life moves on and Kishore invites Vinoth and Murali for his wedding. However, Vinoth is injured in an accident, so, Murali attends the marriage and also performs with his music crew, "Meyadha Maan". Murali meets Madhu and they pick up a quarrel over a room allotment. Murali walks out of the marriage after understanding that both Vinoth and Kishore are hell bent in ensuring that he does not torture Madhu during the marriage. Madhu is pained to hear that Murali still does not know about the drama on that suicide night. Meanwhile, Sudarvizhi (Indhuja Ravichandran), Murali's sister learns about her brother's one side love with Madhu and falls in love with Vinoth. She ensures a fall out with Vinoth as he refuses to see her other than a sister. Murali learns that Sudarvizhi is in love with Vinoth and happily assures her that he will ensure that she is married to Vinoth. Vinoth does not know about Sudarvizhi's love and feels that she had quarrelled with him as she was suffering from trauma due to a fever and a headache. One day, Vinoth meets Madhu and thanks her for her noble gesture. Suddenly Madhu falls down unconscious. Vinoth admits her in a hospital and is rushing to fetch money for her treatment. Murali is suspicious that Vinoth has fallen in love with someone and follows him to the hospital. Murali gets upset when he sees his friend aid the treatment of Madhu, who he believes is his sworn enemy. Subsequently, Murali comes to know about the drama played by Vinoth and attacks him furiously for making him believe that Madhu is a bad girl. In a jiffy, he starts rejoicing as he realises that Madhu is not a bad girl and is still not married. Few days later, Murali finds Madhu falling unconscious and brings her home safely. Soon, Madhu and Murali bury the past and develop a friendship which enrages Madhu's father (Varghese Mathew). Madhu's brother invites Murali for a family function to show him his place. Murali gleefully accepts the invitation. While he enthralls Madhumitha and children by his presence, Madhu's parents are irritated by his presence. Madhu comes to Murali's home the next day to shout at him for accepting the veiled invitation from his family. However she bonds with Sudarvizhi easily and has a good time at Murali's house. Suddenly, Vinoth brings in a marriage alliance for Sudarvizhi. Murali rejects the alliance saying that he has decided to marry his sister to Vinoth. This shocks Vinoth and he is even shocked to see Madhu in Murali's house. Vinoth walks away angrily from Murali's house. Madhu persuades Murali to talk with Vinoth and gives an idea to unite Vinoth and Sudarvizhi. The idea works well and Vinoth reciprocates Sudarvizhi's love. Eventually Madhu informs Murali that she is in love with Murali. Madhu's father finds them as a pair and he hastens Madhu's arranged marriage ceremony with a different groom. Murali and Madhu plan to stop the marriage by having premarital intercourse, but they both pick up a quarrel while executing their plan in midway and part ways. Madhu gets ready for marriage, while Murali vows to complete Sudarvizhi's marriage before her marriage. After a few interesting twists and turns, Vinoth gets married to Sudarvizhi and Madhu reveals that she got pregnant by Murali through the earlier plan of stopping the arranged marriage ceremony. Madhu later ends up in attempting to commit suicide as Murali refuses to marry her. As the credits roll, Madhu and Murali sign the marriage papers in the register office and the movie ends with Murali singing on stage with his wife Madhu recording his performance from the audience area. Cast Vaibhav as 'Idhayam' Murali Priya Bhavani Shankar as S. Madhumitha (Madhu) Vivek Prasanna as Vinoth Indhuja Ravichandran as Sudarvizhi Arun Prasath as Kishore Amrutha Srinivasan as Priyanka Varghese Mathew as Madhumitha's father Sujatha Panju as Madhumitha's mother Anthony Daasan in a special appearance in the "Thangachi" song Pradeep K Vijayan in a special appearance Production Director Rathna Kumar was asked by Karthik Subbaraj to develop his short film Madhu into a feature-length film for his production studio, Stone Bench Creations. Madhu (2013) featuring actors Sananth, Roshni Abraham and Vivek Prasanna, was earlier included as one of the six stories in Stone Bench Creations' anthology film Bench Talkies – The First Bench, which had a theatrical release in March 2015. Rathna Kumar initially had no intentions of making Madhu into a feature film and had developed it only for his portfolio, but obliged to Subbaraj's request as producers were not keen on listening to his other scripts. Rathna Kumar set the film in North Chennai as he was inspired by the creative talents of people in the Royapuram and Kasimedu area, where he found several singers, lyric writers and percussionists during his visits to the areas. The film's lead character runs a light music troupe, making the setting of Royapuram apt for the script. The lead character's shyness to talk to his lover, meant that Rathna Kumar chose to give the character the name of 'Idhayam' Murali, derived from the timid character made famous by the late actor Murali in Kathir's romantic drama Idhayam (1991). Rathna Kumar wrote the first draft of the feature film keeping Sananth, who had starred in the short film, in mind. However, the producers opted against signing a relative newcomer and chose Vaibhav to portray the lead role. To prepare for his role, Vaibhav observed the emotions and body language of real stage singers by watching videos. As Roshni Abraham had chosen not to become a feature film actress, Rathna Kumar then discussed the leading female role with Sai Pallavi, who opted against signing the film. He subsequently announced a casting call online, following which television actress Priya Bhavani Shankar got in touch. Following a successful audition, she was selected to play the leading role of Madhumitha, with Rathna Kumar stating that her on-screen "image" worked for the film. Priya later revealed that she was keen to do the film as it had the backing of Karthik Subbaraj, whose work she liked. Indhuja Ravichandran was selected to be a part of the film after impressing the director with her work in other short films, and was initially worried about her future work and image if she portrayed the sister of Vaibhav's character, before agreeing to star in the film. Vivek Prasanna was the only lead actor to retain his role from the short film. The film's composer Santhosh Narayanan was keen to allow his long-time collaborator Pradeep Kumar to also work on the film as a co-composer, and played a role in bringing him into the project. The film's shoot progressed silently in Royapuram, Chennai and was first revealed to the media only after ninety percent of the shoot was completed. Stone Bench Productions had made the film alongside their commitments for another film directed by Karthik Subbaraj, titled Mercury (2018) starring Prabhu Deva. The teaser trailer of the film was released by actor Dhanush through his Twitter handle in late July 2017. As a part of the film's promotions, the makers dubbed the film as "Royapurathu La La Land" (La La Land in Royapuram) and released posters and captions on the trailer to depict the film in that particular way. Soundtrack The film's soundtrack and score were jointly composed by Santhosh Narayanan and Pradeep Kumar, with the latter making his debut as a composer in Tamil films. Prior to the release of the album, the "Thangachi Song" was released as a single to coincide with the Hindu festival of Raksha Bandhan on 7 August 2017. A second single, "Enna Naan Seiven" was also then released on 25 August 2017. The full album, containing seven tracks, was released by Think Music India on 27 September 2017. The album was launched at Loyola College, Chennai with the cast and crew in attendance. The album received positive response from critics. The critics from Behindwoods.com gave the album 3 out of 5 stars, saying that "Santhosh Narayanan is at his usual best" and that "it was a fitting debut for Pradeep Kumar as music director". Likewise, Karthik Srinivasan of Milliblog.com wrote "the Santhosh-Pradeep combo wins again". Post-release, the "Thangachi Song" and "Address Song" garnered popularity. Release Meyaadha Maan was initially set for release on 17 November 2017, but as some Tamil films that were scheduled for Diwali got delayed, the producers and distributors felt that moving the release forward to coincide with the festival would garner larger audiences. They also felt that spillover audiences from the other high-profile release, Mersal (2017), would instead choose to see Meyaadha Maan. Subsequently, the film had a theatrical release across India on 18 October 2017. The satellite rights of the film were sold to Zee Tamil. Positive feedback from critics and audiences, resulted in a steady growth in the number of screens across Tamil Nadu, Malaysia and Singapore within days of the film's release. The film also benefited from positive word-of-mouth and ended up as a commercial success at the box office. References External links Category:2017 films Category:Indian films Category:Tamil-language films Category:Features based on short films Category:2010s comedy-drama films Category:2010s romantic comedy films Category:Indian romantic comedy films Category:Films scored by Santhosh Narayanan Category:Directorial debut films Category:2010s Tamil-language films Category:Films shot in India Category:Films shot in Tamil Nadu Category:Films shot in Chennai Category:Films set in Chennai
Q: Is there a good query builder for Amazon's DynamoDB? I tracked down this package. Generally it's pretty nice. But it seems to lack support for Projection Expressions. What is your tool of choice for dynamodb in node/typescript? I'm not fan of the data mappers listed here because they tend to wrap the table data, or are abandoned as projects. A: We use dynogels, it is maintained until to date. https://github.com/clarkie/dynogels
Q: Invalid regular expression in Javascript on Lookarounds I'm having a problem with the regex that work in Expresso but not in the javascript code. I know that there are also two other question with the same topic, but can't figure out how to implement an alternative to my regex so that it will work also in javascript. So my expression is: ((?<=\bvar)\s\w\s?)=\s?function(\s$[^)]$) Used in javascript like that: var functionsReg = /((?<=\bvar)\s\w\s?)=\s?function(\s$[^)]$)/gm; var match = functionsReg.exec(func); and I'm expecting to be able to get for the values for each regex group. like: var name = match[0]; var params = match[1]; I found out that the problem is from the (?<=\bvar) But I can not find the alternative for this syntax because in the end I want to be able to access the text like in the below image. A: Just match the var in a non-capture group: /(?:var)\s+(\w+)\s=\sfunction(\s$[^)]$)/g
Effects of extracellular pH on lactate efflux from frog sartorius muscle. The isolated sartorius muscle of frog was stimulated under an anaerobic condition, and intracellular lactate concentration and intracellular pH was determined sequentially by 1H-nuclear magnetic resonance, and the efflux of lactate was measured by an enzymatic method on the incubation media with different pH levels. The lactate efflux was shown to increase in proportion to the concentration difference of lactate across the membrane up to 25 mmol X l H2O-1, and the permeability of the membrane to lactate increased with the increment of extracellular pH. H+ efflux was determined from pH change and the buffer capacity of incubation medium. The efflux of H+ rose approximately linearly with the efflux of lactate up to approximately 70 mumol X min-1 X l H2O-1, and the relationship then revealed a clear leveling off. From these results the efflux of lactate was analyzed in terms of a predominantly nonionic or a predominantly ionic efflux mechanism. Analysis showed that the mechanism of efflux was in both the ionic and nonionic form.
1. Field The subject matter disclosed herein relates to using local maps and annotations for location determination. 2. Information Different techniques may be used to estimate the location of a mobile device, such as a cell phone, personal digital assistant (PDA), or any other mobile device. For example, some mobile devices may process signals received from a Satellite Positioning System (SPS) to estimate their locations. However, sometimes there are certain areas where navigation signals from an SPS may not be available, such as in certain indoor locations. A mobile device may estimate its location within an area where navigation signals transmitted from an SPS are not available. For example, a mobile device may transmit a signal to an access point and measure a length of time until a response signal from the access point is received. A range from the mobile device to the access point may be determined based upon the measured length of time between transmission of a signal from the mobile device and receipt of a response signal at the mobile device. Alternatively, signal strength of a signal received from the access point may be measured and a range from the mobile device to the access point may be estimated based on the measured signal strength. An access point may comprise a device that allows wireless communication devices to communicate with a network. However, an access point may experience a processing delay between a time at which a signal is received from a mobile device and a time at which a response signal is transmitted to the mobile device. Such a processing delay may vary depending upon a particular access point, and may need to be accounted for when a mobile device estimates a range to the access point based on the measured time interval. Moreover, signal strength of a received signal may vary based upon physical structures within an area, such as a presence of ceiling and walls, causing a variance in received signal strength which may result in inaccurate estimates of range to the access point if there is no accounting for such a variance caused by a presence of physical structures, for example.
The present invention relates generally to methods and apparatus for processing I/O requests in computer storage systems and, more particularly, to methods and apparatus which improve the file access performance of a distributed storage system that provides single name space to clients. Some of today's computer storage systems are distributed systems having a number of storage nodes. Each node has a processing unit to process requests from clients or other nodes, a communication unit to send information to and receive information from clients or other nodes, and a storage unit to store data or management information. The nodes communicate with each other via a network and work as a single system. A distributed storage system has several advantages. For example, it has good scalability by adding nodes. It also provides good parallelism of process by distributing workload to a plurality of nodes. One example of distributed storage systems is disclosed in U.S. Pat. No. 7,155,466. When the distributed storage system provides a file system to clients, it often organizes its storage capacity in single name space, which means a client gets an identical view regardless of the node or network port to which it is connected. To achieve single name space, nodes send and receive files among themselves. For example, when a node (“receiver node”) receives a request to read a file from a client and the file is not stored in the node, it identifies another node (“owner node”) that stores the file, requests the owner node to send the file to the receiver node, and sends the file to the client. The capability of single name space allows clients to access files in any nodes even if the client communicates with only one node, and simplifies the configuration management of the clients. From the view point of performance, particularly throughput, however, the inter-node communication to provide single name space capability produces additional overhead of the I/O process. If a file is stored in a node which receives an access request from a client, there is no overhead because it is immediately retrieved and sent to the client directly by the receiver. On the other hand, if the file is stored in another node, it must be read by the owner node, transferred to the receiver node, and then sent to the client. In this case, the file is transferred through four NICs (network interface cards): the owner node's NIC, the receiver node's NIC which receives the file, the receiver node's NIC which sends the file to the client, and the client's NIC. Each time the file is processed through an NIC, it goes through the communication protocol stack which causes memory copy, encapsulation of data to be sent, and reorganization of data received. Particularly if the size of a file transferred is large (e.g., gigabytes), the additional overhead makes the time to transfer it long compared with the case in which a client receives a file directly from its owner node. On the other hand, if the size is small (e.g., kilobytes), the overhead does not have much effect because the transfer time is short.
Q: Migration from Eclipse to Android Studio So, as it seems that more and more people are using Android Studio i got curious and wanted to take a peek at it. I have used Eclipse up until now and wanted to migrate a project to Android Studio. So i exported a gradle buildfile from within Eclipse, as android.developer.com suggested. That worked fine, now i wanted to import that into Android Studio 0.3.2 When trying to import i got that Unable to import Eclipse project to Android Studio error. Now it is building. But it got a new suprise, now before it is finished building, its asking specifically for an older Version of Gradle(1.6)... Ok, i can do that. Which leads me right back to the first error. So i tried this - Gradle version 1.6 is required. Current version is 1.8-20130730220035+0000 I can however create a New Project with Android Studio. I've tried this for about an hour now and im getting sort of pissed, because it doesnt seem to know what it wants. Is it some sort of Bug or did i make some sort of mistake. A: You're using a very old version of Android Studio. I'd recommend upgrading to 0.4.3. Versions later than 0.4.0 allow direct import of Eclipse projects instead of requiring you to do the cumbersome (and as you've seen problematic) export of projects from Eclipse; it's smarter about setting up the right plugin and Gradle versions. 0.4.3 has some important bugfixes over 0.4.0-0.4.2.
After a breach in background checks for Florida’s concealed weapons permitting program was revealed earlier this year, it became apparent that change was imminent. But the direction that change would take has become a tug-of-war between Democrats in the Florida Senate and powerful National Rifle Association lobbyist Marion Hammer. The agriculture commissioner’s office attracted unwanted attention in early 2018 after it was found that for 13 months, the department’s Division of Licensing stopped using results from an FBI crime database that ensures those who apply do not have a disqualifying history in other states. Click to resize Hammer now wants to transfer oversight of the concealed weapons permitting process to Chief Financial Officer Jimmy Patronis, a Republican. Democrats in the state Senate — and incoming Commissioner of Agriculture Nicole “Nikki” Fried, also a Democrat — have other ideas, and plan to file legislation in an attempt to make them law. Democratic state Sens. Lauren Book and Linda Stewart have drafted a bill proposing the Division of Licensing be moved from the Department of Agriculture and Consumer Services to the Florida Department of Law Enforcement. When Florida first adopted a statewide program for concealed weapons permits in the 1980s, it was overseen by the Secretary of State, an elected position. But when the Secretary of State became an appointed position in 2002, Hammer had lawmakers move it to Agriculture. Florida is unusual in having its concealed weapons program overseen by the Department of Agriculture — almost every other state leaves the job up to police or the courts. Stewart, a Democrat from Orlando who helped draft the bill, said the language aims to streamline the current process and depoliticize the department. In the current system, applications for concealed weapons permits are supposed to be run through FDLE as a final step. “The Putnam office was the middleman to what could have been streamlined and faster to deal with these applications,” she said of the administration under Commissioner Adam Putnam, who was ultimately responsible for the 2018 breach. Stewart said the impetus behind the bill is to depoliticize the process and distance the NRA from having a hand in concealed weapons permits. “When you start putting this in agencies that are elected, that is political,” she said of Hammer’s idea to shift responsibility to the CFO. “We need to go with an independent group to do their job. That’s what’s been missing. It shouldn’t be made complicated, and it shouldn’t be made political.” Book, a Democrat from Plantation, plans to file the piece of legislation after she and Stewart meet with commissioner-elect Fried in early December. Fried was the sole Democrat to win statewide office in the midterm election. The senators then plan to meet with new Senate President Bill Galvano, a Bradenton Republican. “I can’t even imagine him being opposed to it,” Stewart said. “We are just waiting for everybody’s approval for it to get released.” The idea is adamantly opposed by the NRA, however. FDLE is “one of the last places it should go,” Hammer said Monday. Instead, she said, the Division of Licensing should be moved to the state’s CFO, an elected Cabinet member who would not mess with the program and would properly manage the trust fund associated with it. “The logical place for it to go is under the CFO,” she said. “The CFO would continue to run it properly.” Anna Alexopoulos Farrar, spokeswoman for CFO Patronis, said the office is “open to learning more about the proposal.” “The concealed carry permitting process is an important step for law-abiding citizens to protect themselves,” she said. “This decision, ultimately, is the will of the Legislature.” Moving the program out from under Fried would require passing a law through Florida’s Republican-controlled Legislature. Hammer said she hasn’t discussed the issue with Patronis, and she wouldn’t say whether she has any lawmakers lined up to introduce legislation to move it to him. Hammer said she wasn’t opposed to the concealed weapons program being under the oversight of a Democrat. Rather, it’s what Fried has said that has bothered her. “It’s a commissioner who has vowed to tinker with the program, to try to fix something that isn’t broken, and to generally disrupt the program that currently serves over 1.8 million Floridians,” Hammer said. Over the course of her campaign, Fried has promised a full audit of the program and has distanced herself from the NRA through advertisements and adversarial social media posts. During a televised debate with opponent Rep. Matt Caldwell, Fried discussed moving oversight of the permitting process to FDLE instead. She says the current office doesn’t take every step of the background checks seriously. Fried, a gun owner and concealed weapon permit holder herself, has emphasized that her stance is non-partisan. “Employees of the department will work for the people of Florida,” Fried wrote in a letter she said was sent to Hammer. “Neither the department, nor its employees will carry out the interests of the NRA, or any outside group that seeks to unduly influence the rules that apply to them.” Hammer said she has not spoken to Fried. “She has made it clear that she doesn’t want to talk to us,” Hammer said Monday. “She has never reached out to us, and claims during the campaign that she had sent a letter to me were false. I never received a letter from her, period.” When the Tampa Bay Times highlighted problems with the program under Putnam, who described himself as a “proud NRA sellout,” it led to questions about why an agency that conducts food inspections and manages state forests was handling weapons permits as well. (The CFO conducts state accounting and auditing and investigates insurance fraud.) The NRA has been insistent on having an elected official, not an appointed one, like the FDLE commissioner, run it. Having FDLE run the background checks, but having a separate state agency dispense the permits, has led to several problems over the years. In 2000, the licensing division wasn’t comparing applicants against a state database of domestic violence abusers because FDLE couldn’t share the database with them. In 2012, the South Florida Sun-Sentinel discovered it wasn’t comparing applicants against an FBI database because the Department of Agriculture wasn’t a law enforcement agency. But Hammer says that such an important program should be under an elected official. “The concealed weapons licensing program needs to remain under an elected Cabinet official,” Hammer said. “It’s a program that should never be under any agency, much less a law enforcement agency that is not answerable to the people.” Correction: An earlier version of this story stated that background checks ensure those who apply to openly carry a gun in public do not have a disqualifying history in other states. Those applying for concealed weapons licenses are not able to openly carry a gun in public.
Q: How to retrieve a React component from an object property I've got a SliderMenu React component, which receives an array containing its elements. These elements are objects, and one of their properties is the icon that will be shown in the menu: function SliderMenu({ options }) { return ( <> <Drawer open> <List> {options.map((item) => { const { icon: ItemIcon } = item \|\| {}; return ( <ListItem button key={`menuItem_${item.text.replace(/\s/g, '')}`}> <ListItemIcon> <ItemIcon /> </ListItemIcon> <ListItemText primary={item.text} /> </ListItem> ); })} </List> </Drawer> </> ); } This component is called from an upper component (because I'd like to be able to create multiple SliderMenu if I needed them), which specifies the elements array and passes them as props: import React from 'react'; import { HomeRoundedIcon } from '@material-ui/icons/HomeRounded'; import SliderMenu from '../../components/SliderMenu'; function MainMenu() { const menuOptions = [ { text: 'Home', icon: HomeRoundedIcon, }, ]; return ( <SliderMenu options={menuOptions} /> ); } export default MainMenu; The problem here is that whenever I try this code, ItemIcon is undefined, and I'm receiving the following error: Error: Element type is invalid: expected a string (for built-in components) or a class/function (for composite components) but got: undefined. You likely forgot to export your component from the file it's defined in, or you might have mixed up default and named imports. Check the render method of SliderMenu. However, if I try: const menuOptions = [ { text: 'Home', icon: <HomeRoundedIcon />, }, ]; ItemIcon has a value, and I get the following error: Error: Element type is invalid: expected a string (for built-in components) or a class/function (for composite components) but got: object. Check the render method of SliderMenu. I would like to be able to specify different menu elements with different icons and so on, depending on the context, and then use the common component to render it and have a consistent behaviour across all menus. How can I define the icon in the object, using the icon component library, and then pass it via props to the SliderMenu so it can render it (without having to import all the icons and make a switch to see which icon has to render)? A: Change your import to a default import import HomeRoundedIcon from '@material-ui/icons/HomeRounded' or use a named import from @material-ui/icons path import { HomeRounded as HomeRoundedIcon } from "@material-ui/icons" You would also want to remove the default assignment and render the icon conditionally as this will throw an error when there is no icon const { icon: ItemIcon } = item {ItemIcon && ( <ListItemIcon> <ItemIcon /> </ListItemIcon> )}
%YAML 1.2 --- # http://www.sublimetext.com/docs/3/syntax.html name: R file_extensions: - R - r - Rprofile scope: source.r variables: exponent: (?:[eE][-+]?\d+) var: '(?:[a-zA-Z._][a-zA-Z0-9._]\|`[^`]+`)' contexts: main: - include: roxygen - include: codesection - include: comments - include: constants - include: accessor - include: operators - include: keywords - include: storage-types - include: strings - include: brackets - include: function-declarations - include: lambda-functions - include: builtin-functions - include: function-calls - include: general-variables codesection: - match: ^\s((\#+)\s(.+?)\s(?:-{4,}\|={4,}\|#{4,})[ \t]$\n?) captures: 1: comment.line.number-sign.r 2: punctuation.definition.comment.r 3: entity.name.section.r comments: - match: \#+ scope: punctuation.definition.comment.r push: - meta_scope: comment.line.number-sign.r - match: \n pop: true constants: - match: \b(pi\|letters\|LETTERS\|month\.abb\|month\.name)\b scope: support.constant.misc.r - match: \b(TRUE\|FALSE\|NULL\|NA\|NA_integer_\|NA_real_\|NA_complex_\|NA_character_\|Inf\|NaN)\b scope: constant.language.r # complex imaginary - match: \b(0[xX])(\h+)(?:(i)\|(I))\b scope: meta.number.imaginary.hexadecimal.r captures: 1: constant.numeric.base.r 2: constant.numeric.value.r 3: constant.numeric.suffix.r 4: invalid.illegal.numeric.r - match: ((?:(\.)\d+\|\b\d+(\.)?\d){{exponent}}?)(?:(i)\|(I))\b scope: meta.number.imaginary.decimal.r captures: 1: constant.numeric.value.r 2: punctuation.separator.decimal.r 3: punctuation.separator.decimal.r 4: constant.numeric.suffix.r 5: invalid.illegal.numeric.r # integers - match: \b(0[xX])(\h+)(?:(L)\|(l))\b scope: meta.number.integer.hexadecimal.r captures: 1: constant.numeric.base.r 2: constant.numeric.value.r 3: constant.numeric.suffix.r 4: invalid.illegal.numeric.r - match: \b(\d+(\.)?\d)(?:(L)\|(l))\b scope: meta.number.integer.decimal.r captures: 1: constant.numeric.value.r 2: punctuation.separator.decimal.r 3: constant.numeric.suffix.r 4: invalid.illegal.numeric.r # floats - match: \b(0[xX])(\h+)\b scope: meta.number.float.hexadecimal.r captures: 1: constant.numeric.base.r 2: constant.numeric.value.r - match: \|- (?x: # 1., 1.1, 1.1e1, 1.1e-1, 1.e1, 1.e-1 \| 1, 1e1, 1e-1 \b\d+ (?: (\.) (?: \d {{exponent}}? \b )? \| {{exponent}}? \b ) # .1, .1e1, .1e-1 \| (\.) \d+ {{exponent}}? \b ) scope: meta.number.float.decimal.r constant.numeric.value.r captures: 1: punctuation.separator.decimal.r 2: punctuation.separator.decimal.r general-variables: - match: '{{var}}' keywords: - match: \bif\b(?=\s\() scope: keyword.control.conditional.if.r - match: \belse\b scope: keyword.control.conditional.else.r - match: \bbreak\b scope: keyword.control.flow.break.r - match: \bnext\b scope: keyword.control.flow.continue.r - match: \breturn(?=\s\() scope: keyword.control.flow.return.r - match: \brepeat\b scope: keyword.control.loop.repeat.r - match: \bfor\b(?=\s\() scope: keyword.control.loop.for.r - match: \bwhile\b(?=\s\() scope: keyword.control.loop.while.r - match: \bin\b scope: keyword.operator.word.r accessor: - match: '\$' scope: keyword.accessor.dollar.r push: - include: function-calls - include: general-variables - match: '' pop: true operators: # NOTE: sorted by length to ensure not to break ligatures # operators with 3+ characters - match: '%[/ox]%' scope: keyword.operator.arithmetic.r - match: (<<-\|->>) scope: keyword.operator.assignment.r - match: '%(between\|chin\|do\|dopar\|in\|like\|\+replace\|\+\|:\|T>\|<>\|>\|\$)%' scope: keyword.operator.other.r - match: \.\.\. scope: keyword.other.r - match: :::? scope: punctuation.accessor.colons.r # operators with 2 characters - match: (%%\|\\) scope: keyword.operator.arithmetic.r - match: (<-\|->) scope: keyword.operator.assignment.r - match: (==\|!=\|<=\|>=\|<>\|&&\|\\|\\|) scope: keyword.operator.logical.r - match: := scope: keyword.operator.other.r # operators with 1 characters - match: '[-+/^]' scope: keyword.operator.arithmetic.r - match: = scope: keyword.operator.assignment.r - match: '[!&\|<>]' scope: keyword.operator.logical.r - match: '[:~@]' scope: keyword.other.r - match: ; scope: punctuation.terminator.semicolon.r storage-types: - match: \b(character\|complex\|double\|expression\|integer\|list\|logical\|numeric\|single\|raw)\s(?=$) scope: meta.function-call.identifier.r captures: 1: storage.type.r push: function-call-arguments strings: - match: (R\|r)("(-)\() captures: 1: storage.type.string.r 2: punctuation.definition.string.begin.r push: - meta_scope: string.quoted.double.r - match: $(\3)" scope: punctuation.definition.string.end.r pop: true - match: (R\|r)("(-)\{) captures: 1: storage.type.string.r 2: punctuation.definition.string.begin.r push: - meta_scope: string.quoted.double.r - match: \}(\3)" scope: punctuation.definition.string.end.r pop: true - match: (R\|r)("(-)\[) captures: 1: storage.type.string.r 2: punctuation.definition.string.begin.r push: - meta_scope: string.quoted.double.r - match: \](\3)" scope: punctuation.definition.string.end.r pop: true - match: (R\|r)('(-)$) captures: 1: storage.type.string.r 2: punctuation.definition.string.begin.r push: - meta_scope: string.quoted.single.r - match: $(\3)' scope: punctuation.definition.string.end.r pop: true - match: (R\|r)('(-)\{) captures: 1: storage.type.string.r 2: punctuation.definition.string.begin.r push: - meta_scope: string.quoted.single.r - match: \}(\3)' scope: punctuation.definition.string.end.r pop: true - match: (R\|r)('(-)\[) captures: 1: storage.type.string.r 2: punctuation.definition.string.begin.r push: - meta_scope: string.quoted.single.r - match: \](\3)' scope: punctuation.definition.string.end.r pop: true - match: '"' scope: punctuation.definition.string.begin.r push: - meta_scope: string.quoted.double.r - match: \\. scope: constant.character.escape.r - match: '"' scope: punctuation.definition.string.end.r pop: true - match: "'" scope: punctuation.definition.string.begin.r push: - meta_scope: string.quoted.single.r - match: \\. scope: constant.character.escape.r - match: "'" scope: punctuation.definition.string.end.r pop: true brackets: - match: $ scope: punctuation.section.parens.begin.r push: - match: $ scope: punctuation.section.parens.end.r pop: true - include: main - match: \[(?!\[) scope: meta.item-access.r punctuation.section.brackets.single.begin.r push: - meta_content_scope: meta.item-access.r meta.item-access.arguments.r - match: \] scope: meta.item-access.r punctuation.section.brackets.single.end.r pop: true - match: ',' scope: punctuation.separator.parameters.r - include: main - match: \[\[ scope: meta.item-access.r punctuation.section.brackets.double.begin.r push: - meta_content_scope: meta.item-access.r meta.item-access.arguments.r - match: \]\] scope: meta.item-access.r punctuation.section.brackets.double.end.r pop: true - match: ',' scope: punctuation.separator.parameters.r - include: main - match: \{ scope: punctuation.section.braces.begin.r push: - match: \} scope: punctuation.section.braces.end.r pop: true - include: main function-declarations: - match: (({{var}})\s)((<<?-\|=)\s)(?=function\s$) captures: 1: meta.function.identifier.r 2: entity.name.function.r 3: meta.function.r 4: keyword.operator.assignment.r push: - include: lambda-functions - match: '' pop: true lambda-functions: - match: \b(function)\s(?=\() scope: meta.function.r captures: 1: storage.type.function.r push: - match: \( scope: punctuation.section.parameters.begin.r set: - meta_scope: meta.function.parameters.r - match: $ scope: punctuation.section.parameters.end.r pop: true - include: comments - match: '{{var}}' scope: variable.parameter.r - match: '(?==)' push: - include: main - match: (?=[,)]) pop: true - match: ',' scope: punctuation.separator.parameters.r function-calls: - match: (?:\b\|(?=\.))({{var}})\s(?=$) scope: meta.function-call.identifier.r captures: 1: variable.function.r push: function-call-arguments function-call-arguments: - match: \( scope: punctuation.section.arguments.begin.r set: - meta_scope: meta.function-call.arguments.r - match: $ scope: punctuation.section.arguments.end.r pop: true - match: '{{var}}(?=\s=[^=])' scope: variable.parameter.r - match: '(?==)' push: - include: main - match: (?=[,)]) pop: true - match: ',' scope: punctuation.separator.arguments.r - include: main roxygen-content: - meta_scope: comment.line.roxygen.r - match: $\n? pop: true roxygen-keyword: - match: (@param)\s({{var}}) captures: 1: keyword.other.r 2: variable.parameter.r - match: '@[a-zA-Z0-9]+' scope: keyword.other.r - match: '' pop: true roxygen: - match: (#')\s* captures: 1: punctuation.definition.comment.r push: [roxygen-content, roxygen-keyword] # the builtin-functions are generated by using this # cat(paste(gsub("\\.", "\\\\.", Filter(function(x) grepl("^[a-zA-Z\\._][0-9a-zA-Z\\._]$", x), unclass(lsf.str(envir = asNamespace(pkg))))), collapse = "\|")) builtin-functions: # base - match: \b(abbreviate\|abs\|acos\|acosh\|activeBindingFunction\|addNA\|addTaskCallback\|agrep\|agrepl\|alist\|all\|all\.equal\|all\.equal\.character\|all\.equal\.default\|all\.equal\.environment\|all\.equal\.envRefClass\|all\.equal\.factor\|all\.equal\.formula\|all\.equal\.language\|all\.equal\.list\|all\.equal\.numeric\|all\.equal\.POSIXt\|all\.equal\.raw\|all\.names\|all\.vars\|allowInterrupts\|any\|anyDuplicated\|anyDuplicated\.array\|anyDuplicated\.data\.frame\|anyDuplicated\.default\|anyDuplicated\.matrix\|anyNA\|anyNA\.data\.frame\|anyNA\.numeric_version\|anyNA\.POSIXlt\|aperm\|aperm\.default\|aperm\.table\|append\|apply\|Arg\|args\|array\|arrayInd\|as\.array\|as\.array\.default\|as\.call\|as\.character\|as\.character\.condition\|as\.character\.Date\|as\.character\.default\|as\.character\.error\|as\.character\.factor\|as\.character\.hexmode\|as\.character\.numeric_version\|as\.character\.octmode\|as\.character\.POSIXt\|as\.character\.srcref\|as\.complex\|as\.data\.frame\|as\.data\.frame\.array\|as\.data\.frame\.AsIs\|as\.data\.frame\.character\|as\.data\.frame\.complex\|as\.data\.frame\.data\.frame\|as\.data\.frame\.Date\|as\.data\.frame\.default\|as\.data\.frame\.difftime\|as\.data\.frame\.factor\|as\.data\.frame\.integer\|as\.data\.frame\.list\|as\.data\.frame\.logical\|as\.data\.frame\.matrix\|as\.data\.frame\.model\.matrix\|as\.data\.frame\.noquote\|as\.data\.frame\.numeric\|as\.data\.frame\.numeric_version\|as\.data\.frame\.ordered\|as\.data\.frame\.POSIXct\|as\.data\.frame\.POSIXlt\|as\.data\.frame\.raw\|as\.data\.frame\.table\|as\.data\.frame\.ts\|as\.data\.frame\.vector\|as\.Date\|as\.Date\.character\|as\.Date\.default\|as\.Date\.factor\|as\.Date\.numeric\|as\.Date\.POSIXct\|as\.Date\.POSIXlt\|as\.difftime\|as\.double\|as\.double\.difftime\|as\.double\.POSIXlt\|as\.environment\|as\.expression\|as\.expression\.default\|as\.factor\|as\.function\|as\.function\.default\|as\.hexmode\|as\.integer\|as\.list\|as\.list\.data\.frame\|as\.list\.Date\|as\.list\.default\|as\.list\.difftime\|as\.list\.environment\|as\.list\.factor\|as\.list\.function\|as\.list\.numeric_version\|as\.list\.POSIXct\|as\.list\.POSIXlt\|as\.logical\|as\.logical\.factor\|as\.matrix\|as\.matrix\.data\.frame\|as\.matrix\.default\|as\.matrix\.noquote\|as\.matrix\.POSIXlt\|as\.name\|as\.null\|as\.null\.default\|as\.numeric\|as\.numeric_version\|as\.octmode\|as\.ordered\|as\.package_version\|as\.pairlist\|as\.POSIXct\|as\.POSIXct\.Date\|as\.POSIXct\.default\|as\.POSIXct\.numeric\|as\.POSIXct\.POSIXlt\|as\.POSIXlt\|as\.POSIXlt\.character\|as\.POSIXlt\.Date\|as\.POSIXlt\.default\|as\.POSIXlt\.factor\|as\.POSIXlt\.numeric\|as\.POSIXlt\.POSIXct\|as\.qr\|as\.raw\|as\.single\|as\.single\.default\|as\.symbol\|as\.table\|as\.table\.default\|as\.vector\|as\.vector\.factor\|asin\|asinh\|asNamespace\|asplit\|asS3\|asS4\|assign\|atan\|atan2\|atanh\|attach\|attachNamespace\|attr\|attr\.all\.equal\|attributes\|autoload\|autoloader\|backsolve\|baseenv\|basename\|besselI\|besselJ\|besselK\|besselY\|beta\|bindingIsActive\|bindingIsLocked\|bindtextdomain\|bitwAnd\|bitwNot\|bitwOr\|bitwShiftL\|bitwShiftR\|bitwXor\|body\|bquote\|break\|browser\|browserCondition\|browserSetDebug\|browserText\|builtins\|by\|by\.data\.frame\|by\.default\|bzfile\|c\|c\.Date\|c\.difftime\|c\.noquote\|c\.numeric_version\|c\.POSIXct\|c\.POSIXlt\|c\.warnings\|call\|callCC\|capabilities\|casefold\|cat\|cbind\|cbind\.data\.frame\|ceiling\|char\.expand\|character\|charmatch\|charToRaw\|chartr\|check_tzones\|chkDots\|chol\|chol\.default\|chol2inv\|choose\|class\|clearPushBack\|close\|close\.connection\|close\.srcfile\|close\.srcfilealias\|closeAllConnections\|col\|colMeans\|colnames\|colSums\|commandArgs\|comment\|complex\|computeRestarts\|conditionCall\|conditionCall\.condition\|conditionMessage\|conditionMessage\.condition\|conflictRules\|conflicts\|Conj\|contributors\|cos\|cosh\|cospi\|crossprod\|Cstack_info\|cummax\|cummin\|cumprod\|cumsum\|curlGetHeaders\|cut\|cut\.Date\|cut\.default\|cut\.POSIXt\|data\.class\|data\.frame\|data\.matrix\|date\|debug\|debuggingState\|debugonce\|default\.stringsAsFactors\|delayedAssign\|deparse\|deparse1\|det\|detach\|determinant\|determinant\.matrix\|dget\|diag\|diff\|diff\.Date\|diff\.default\|diff\.difftime\|diff\.POSIXt\|difftime\|digamma\|dim\|dim\.data\.frame\|dimnames\|dimnames\.data\.frame\|dir\|dir\.create\|dir\.exists\|dirname\|do\.call\|dontCheck\|double\|dput\|dQuote\|drop\|droplevels\|droplevels\.data\.frame\|droplevels\.factor\|dump\|duplicated\|duplicated\.array\|duplicated\.data\.frame\|duplicated\.default\|duplicated\.matrix\|duplicated\.numeric_version\|duplicated\.POSIXlt\|duplicated\.warnings\|dyn\.load\|dyn\.unload\|dynGet\|eapply\|eigen\|emptyenv\|enc2native\|enc2utf8\|encodeString\|Encoding\|endsWith\|enquote\|env\.profile\|environment\|environmentIsLocked\|environmentName\|errorCondition\|eval\|eval\.parent\|evalq\|exists\|exp\|expand\.grid\|expm1\|expression\|extSoftVersion\|factor\|factorial\|fifo\|file\|file\.access\|file\.append\|file\.choose\|file\.copy\|file\.create\|file\.exists\|file\.info\|file\.link\|file\.mode\|file\.mtime\|file\.path\|file\.remove\|file\.rename\|file\.show\|file\.size\|file\.symlink\|Filter\|Find\|find\.package\|findInterval\|findPackageEnv\|findRestart\|floor\|flush\|flush\.connection\|for\|force\|forceAndCall\|formals\|format\|format\.AsIs\|format\.data\.frame\|format\.Date\|format\.default\|format\.difftime\|format\.factor\|format\.hexmode\|format\.info\|format\.libraryIQR\|format\.numeric_version\|format\.octmode\|format\.packageInfo\|format\.POSIXct\|format\.POSIXlt\|format\.pval\|format\.summaryDefault\|formatC\|formatDL\|forwardsolve\|function\|gamma\|gc\|gc\.time\|gcinfo\|gctorture\|gctorture2\|get\|get0\|getAllConnections\|getCallingDLL\|getCallingDLLe\|getConnection\|getDLLRegisteredRoutines\|getDLLRegisteredRoutines\.character\|getDLLRegisteredRoutines\.DLLInfo\|getElement\|geterrmessage\|getExportedValue\|getHook\|getLoadedDLLs\|getNamespace\|getNamespaceExports\|getNamespaceImports\|getNamespaceInfo\|getNamespaceName\|getNamespaceUsers\|getNamespaceVersion\|getNativeSymbolInfo\|getOption\|getRversion\|getSrcLines\|getTaskCallbackNames\|gettext\|gettextf\|getwd\|gl\|globalCallingHandlers\|globalenv\|gregexpr\|grep\|grepl\|grepRaw\|grouping\|gsub\|gzcon\|gzfile\|I\|iconv\|iconvlist\|icuGetCollate\|icuSetCollate\|identical\|identity\|if\|ifelse\|Im\|importIntoEnv\|infoRDS\|inherits\|integer\|interaction\|interactive\|intersect\|intToBits\|intToUtf8\|inverse\.rle\|invisible\|invokeRestart\|invokeRestartInteractively\|is\.array\|is\.atomic\|is\.call\|is\.character\|is\.complex\|is\.data\.frame\|is\.double\|is\.element\|is\.environment\|is\.expression\|is\.factor\|is\.finite\|is\.function\|is\.infinite\|is\.integer\|is\.language\|is\.list\|is\.loaded\|is\.logical\|is\.matrix\|is\.na\|is\.na\.data\.frame\|is\.na\.numeric_version\|is\.na\.POSIXlt\|is\.name\|is\.nan\|is\.null\|is\.numeric\|is\.numeric_version\|is\.numeric\.Date\|is\.numeric\.difftime\|is\.numeric\.POSIXt\|is\.object\|is\.ordered\|is\.package_version\|is\.pairlist\|is\.primitive\|is\.qr\|is\.R\|is\.raw\|is\.recursive\|is\.single\|is\.symbol\|is\.table\|is\.unsorted\|is\.vector\|isatty\|isBaseNamespace\|isdebugged\|isFALSE\|isIncomplete\|isNamespace\|isNamespaceLoaded\|ISOdate\|ISOdatetime\|isOpen\|isRestart\|isS4\|isSeekable\|isSymmetric\|isSymmetric\.matrix\|isTRUE\|jitter\|julian\|julian\.Date\|julian\.POSIXt\|kappa\|kappa\.default\|kappa\.lm\|kappa\.qr\|kronecker\|l10n_info\|La_library\|La_version\|La\.svd\|labels\|labels\.default\|lapply\|lazyLoad\|lazyLoadDBexec\|lazyLoadDBfetch\|lbeta\|lchoose\|length\|length\.POSIXlt\|lengths\|levels\|levels\.default\|lfactorial\|lgamma\|libcurlVersion\|library\|library\.dynam\|library\.dynam\.unload\|licence\|license\|list\|list\.dirs\|list\.files\|list2DF\|list2env\|load\|loadedNamespaces\|loadingNamespaceInfo\|loadNamespace\|local\|lockBinding\|lockEnvironment\|log\|log10\|log1p\|log2\|logb\|logical\|lower\.tri\|ls\|make\.names\|make\.unique\|makeActiveBinding\|Map\|mapply\|margin\.table\|marginSums\|mat\.or\.vec\|match\|match\.arg\|match\.call\|match\.fun\|Math\.data\.frame\|Math\.Date\|Math\.difftime\|Math\.factor\|Math\.POSIXt\|matrix\|max\|max\.col\|mean\|mean\.Date\|mean\.default\|mean\.difftime\|mean\.POSIXct\|mean\.POSIXlt\|mem\.maxNSize\|mem\.maxVSize\|memCompress\|memDecompress\|memory\.profile\|merge\|merge\.data\.frame\|merge\.default\|message\|mget\|min\|missing\|Mod\|mode\|months\|months\.Date\|months\.POSIXt\|names\|names\.POSIXlt\|namespaceExport\|namespaceImport\|namespaceImportClasses\|namespaceImportFrom\|namespaceImportMethods\|nargs\|nchar\|ncol\|NCOL\|Negate\|new\.env\|next\|NextMethod\|ngettext\|nlevels\|noquote\|norm\|normalizePath\|nrow\|NROW\|nullfile\|numeric\|numeric_version\|nzchar\|objects\|oldClass\|OlsonNames\|on\.exit\|open\|open\.connection\|open\.srcfile\|open\.srcfilealias\|open\.srcfilecopy\|Ops\.data\.frame\|Ops\.Date\|Ops\.difftime\|Ops\.factor\|Ops\.numeric_version\|Ops\.ordered\|Ops\.POSIXt\|options\|order\|ordered\|outer\|package_version\|packageEvent\|packageHasNamespace\|packageNotFoundError\|packageStartupMessage\|packBits\|pairlist\|parent\.env\|parent\.frame\|parse\|parseNamespaceFile\|paste\|paste0\|path\.expand\|path\.package\|pcre_config\|pipe\|plot\|pmatch\|pmax\|pmax\.int\|pmin\|pmin\.int\|polyroot\|pos\.to\.env\|Position\|pretty\|pretty\.default\|prettyNum\|print\|print\.AsIs\|print\.by\|print\.condition\|print\.connection\|print\.data\.frame\|print\.Date\|print\.default\|print\.difftime\|print\.Dlist\|print\.DLLInfo\|print\.DLLInfoList\|print\.DLLRegisteredRoutines\|print\.eigen\|print\.factor\|print\.function\|print\.hexmode\|print\.libraryIQR\|print\.listof\|print\.NativeRoutineList\|print\.noquote\|print\.numeric_version\|print\.octmode\|print\.packageInfo\|print\.POSIXct\|print\.POSIXlt\|print\.proc_time\|print\.restart\|print\.rle\|print\.simple\.list\|print\.srcfile\|print\.srcref\|print\.summary\.table\|print\.summary\.warnings\|print\.summaryDefault\|print\.table\|print\.warnings\|prmatrix\|proc\.time\|prod\|prop\.table\|proportions\|provideDimnames\|psigamma\|pushBack\|pushBackLength\|q\|qr\|qr\.coef\|qr\.default\|qr\.fitted\|qr\.Q\|qr\.qty\|qr\.qy\|qr\.R\|qr\.resid\|qr\.solve\|qr\.X\|quarters\|quarters\.Date\|quarters\.POSIXt\|quit\|quote\|R_system_version\|R\.home\|R\.Version\|range\|range\.default\|rank\|rapply\|raw\|rawConnection\|rawConnectionValue\|rawShift\|rawToBits\|rawToChar\|rbind\|rbind\.data\.frame\|rcond\|Re\|read\.dcf\|readBin\|readChar\|readline\|readLines\|readRDS\|readRenviron\|Recall\|Reduce\|reg\.finalizer\|regexec\|regexpr\|registerS3method\|registerS3methods\|regmatches\|remove\|removeTaskCallback\|rep\|rep_len\|rep\.Date\|rep\.factor\|rep\.int\|rep\.numeric_version\|rep\.POSIXct\|rep\.POSIXlt\|repeat\|replace\|replicate\|require\|requireNamespace\|restartDescription\|restartFormals\|retracemem\|return\|returnValue\|rev\|rev\.default\|rle\|rm\|RNGkind\|RNGversion\|round\|round\.Date\|round\.POSIXt\|row\|row\.names\|row\.names\.data\.frame\|row\.names\.default\|rowMeans\|rownames\|rowsum\|rowsum\.data\.frame\|rowsum\.default\|rowSums\|sample\|sample\.int\|sapply\|save\|save\.image\|saveRDS\|scale\|scale\.default\|scan\|search\|searchpaths\|seek\|seek\.connection\|seq\|seq_along\|seq_len\|seq\.Date\|seq\.default\|seq\.int\|seq\.POSIXt\|sequence\|sequence\.default\|serialize\|serverSocket\|set\.seed\|setdiff\|setequal\|setHook\|setNamespaceInfo\|setSessionTimeLimit\|setTimeLimit\|setwd\|showConnections\|shQuote\|sign\|signalCondition\|signif\|simpleCondition\|simpleError\|simpleMessage\|simpleWarning\|simplify2array\|sin\|single\|sinh\|sink\|sink\.number\|sinpi\|slice\.index\|socketAccept\|socketConnection\|socketSelect\|socketTimeout\|solve\|solve\.default\|solve\.qr\|sort\|sort\.default\|sort\.int\|sort\.list\|sort\.POSIXlt\|source\|split\|split\.data\.frame\|split\.Date\|split\.default\|split\.POSIXct\|sprintf\|sqrt\|sQuote\|srcfile\|srcfilealias\|srcfilecopy\|srcref\|standardGeneric\|startsWith\|stderr\|stdin\|stdout\|stop\|stopifnot\|storage\.mode\|str2expression\|str2lang\|strftime\|strptime\|strrep\|strsplit\|strtoi\|strtrim\|structure\|strwrap\|sub\|subset\|subset\.data\.frame\|subset\.default\|subset\.matrix\|substitute\|substr\|substring\|sum\|summary\|summary\.connection\|summary\.data\.frame\|Summary\.data\.frame\|summary\.Date\|Summary\.Date\|summary\.default\|Summary\.difftime\|summary\.factor\|Summary\.factor\|summary\.matrix\|Summary\.numeric_version\|Summary\.ordered\|summary\.POSIXct\|Summary\.POSIXct\|summary\.POSIXlt\|Summary\.POSIXlt\|summary\.proc_time\|summary\.srcfile\|summary\.srcref\|summary\.table\|summary\.warnings\|suppressMessages\|suppressPackageStartupMessages\|suppressWarnings\|suspendInterrupts\|svd\|sweep\|switch\|sys\.call\|sys\.calls\|Sys\.chmod\|Sys\.Date\|sys\.frame\|sys\.frames\|sys\.function\|Sys\.getenv\|Sys\.getlocale\|Sys\.getpid\|Sys\.glob\|Sys\.info\|sys\.load\.image\|Sys\.localeconv\|sys\.nframe\|sys\.on\.exit\|sys\.parent\|sys\.parents\|Sys\.readlink\|sys\.save\.image\|Sys\.setenv\|Sys\.setFileTime\|Sys\.setlocale\|Sys\.sleep\|sys\.source\|sys\.status\|Sys\.time\|Sys\.timezone\|Sys\.umask\|Sys\.unsetenv\|Sys\.which\|system\|system\.file\|system\.time\|system2\|t\|t\.data\.frame\|t\.default\|table\|tabulate\|tan\|tanh\|tanpi\|tapply\|taskCallbackManager\|tcrossprod\|tempdir\|tempfile\|textConnection\|textConnectionValue\|tolower\|topenv\|toString\|toString\.default\|toupper\|trace\|traceback\|tracemem\|tracingState\|transform\|transform\.data\.frame\|transform\.default\|trigamma\|trimws\|trunc\|trunc\.Date\|trunc\.POSIXt\|truncate\|truncate\.connection\|try\|tryCatch\|tryInvokeRestart\|typeof\|unclass\|undebug\|union\|unique\|unique\.array\|unique\.data\.frame\|unique\.default\|unique\.matrix\|unique\.numeric_version\|unique\.POSIXlt\|unique\.warnings\|units\|units\.difftime\|unix\.time\|unlink\|unlist\|unloadNamespace\|unlockBinding\|unname\|unserialize\|unsplit\|untrace\|untracemem\|unz\|upper\.tri\|url\|UseMethod\|utf8ToInt\|validEnc\|validUTF8\|vapply\|vector\|Vectorize\|warning\|warningCondition\|warnings\|weekdays\|weekdays\.Date\|weekdays\.POSIXt\|which\|which\.max\|which\.min\|while\|with\|with\.default\|withAutoprint\|withCallingHandlers\|within\|within\.data\.frame\|within\.list\|withRestarts\|withVisible\|write\|write\.dcf\|writeBin\|writeChar\|writeLines\|xor\|xpdrows\.data\.frame\|xtfrm\|xtfrm\.AsIs\|xtfrm\.Date\|xtfrm\.default\|xtfrm\.difftime\|xtfrm\.factor\|xtfrm\.numeric_version\|xtfrm\.POSIXct\|xtfrm\.POSIXlt\|xzfile\|zapsmall)\s(?=\() scope: meta.function-call.identifier.r captures: 1: support.function.r push: function-call-arguments # graphics - match: \b(abline\|arrows\|assocplot\|axis\|Axis\|axis\.Date\|Axis\.Date\|Axis\.default\|axis\.POSIXct\|Axis\.POSIXt\|Axis\.table\|axTicks\|barplot\|barplot\.default\|barplot\.formula\|box\|boxplot\|boxplot\.default\|boxplot\.formula\|boxplot\.matrix\|bxp\|cdplot\|cdplot\.default\|cdplot\.formula\|clip\|close\.screen\|co\.intervals\|contour\|contour\.default\|coplot\|curve\|dotchart\|erase\.screen\|filled\.contour\|fourfoldplot\|frame\|grconvertX\|grconvertY\|grid\|hist\|hist\.Date\|hist\.default\|hist\.POSIXt\|identify\|identify\.default\|image\|image\.default\|layout\|layout\.show\|lcm\|legend\|lines\|lines\.default\|lines\.formula\|lines\.histogram\|lines\.table\|locator\|matlines\|matplot\|matpoints\|mosaicplot\|mosaicplot\.default\|mosaicplot\.formula\|mtext\|pairs\|pairs\.default\|pairs\.formula\|panel\.smooth\|par\|persp\|persp\.default\|pie\|piechart\|plot\.data\.frame\|plot\.default\|plot\.design\|plot\.factor\|plot\.formula\|plot\.function\|plot\.histogram\|plot\.new\|plot\.raster\|plot\.table\|plot\.window\|plot\.xy\|plotHclust\|points\|points\.default\|points\.formula\|points\.table\|polygon\|polypath\|rasterImage\|rect\|rug\|screen\|segments\|smoothScatter\|spineplot\|spineplot\.default\|spineplot\.formula\|split\.screen\|stars\|stem\|strheight\|stripchart\|stripchart\.default\|stripchart\.formula\|strwidth\|sunflowerplot\|sunflowerplot\.default\|sunflowerplot\.formula\|symbols\|text\|text\.default\|text\.formula\|title\|xinch\|xspline\|xyinch\|yinch)\s(?=\() scope: meta.function-call.identifier.r captures: 1: support.function.r push: function-call-arguments # grDevices - match: \b(adjustcolor\|anyNA\.raster\|as\.graphicsAnnot\|as\.matrix\.raster\|as\.raster\|as\.raster\.array\|as\.raster\.character\|as\.raster\.logical\|as\.raster\.matrix\|as\.raster\.numeric\|as\.raster\.raster\|as\.raster\.raw\|axisTicks\|bitmap\|bmp\|boxplot\.stats\|c2to3\|cairo_pdf\|cairo_ps\|cairoFT\|cairoSymbolFont\|cairoVersion\|check_for_XQuartz\|check_gs_type\|check\.options\|checkFont\|checkFont\.CIDFont\|checkFont\.default\|checkFont\.Type1Font\|checkFontInUse\|checkIntFormat\|checkQuartzFont\|checkSymbolFont\|checkX11Font\|chromaticAdaptation\|chull\|CIDFont\|cm\|cm\.colors\|col2rgb\|colorConverter\|colorRamp\|colorRampPalette\|colors\|colours\|comparePangoVersion\|contourLines\|convertColor\|densCols\|dev\.capabilities\|dev\.capture\|dev\.control\|dev\.copy\|dev\.copy2eps\|dev\.copy2pdf\|dev\.cur\|dev\.displaylist\|dev\.flush\|dev\.hold\|dev\.interactive\|dev\.list\|dev\.new\|dev\.next\|dev\.off\|dev\.prev\|dev\.print\|dev\.set\|dev\.size\|dev2bitmap\|devAskNewPage\|deviceIsInteractive\|embedFonts\|extendrange\|getGraphicsEvent\|getGraphicsEventEnv\|graphics\.off\|gray\|gray\.colors\|grey\|grey\.colors\|grSoftVersion\|guessEncoding\|hcl\|hcl\.colors\|hcl\.pals\|heat\.colors\|hsv\|initPSandPDFfonts\|is\.na\.raster\|is\.raster\|isPDF\|jpeg\|make\.rgb\|matchEncoding\|matchEncoding\.CIDFont\|matchEncoding\.Type1Font\|matchFont\|n2mfrow\|nclass\.FD\|nclass\.scott\|nclass\.Sturges\|Ops\.raster\|optionSymbolFont\|palette\|palette\.colors\|palette\.match\|palette\.pals\|pangoVersion\|pdf\|pdf\.options\|pdfFonts\|pictex\|png\|postscript\|postscriptFonts\|pow3\|prettyDate\|print\.colorConverter\|print\.raster\|print\.recordedplot\|print\.RGBcolorConverter\|printFont\|printFont\.CIDFont\|printFont\.Type1Font\|printFonts\|ps\.options\|quartz\|quartz\.options\|quartz\.save\|quartzFont\|quartzFonts\|rainbow\|recordGraphics\|recordPalette\|recordPlot\|replayPlot\|restoreRecordedPlot\|rgb\|rgb2hsv\|RGBcolorConverter\|savePlot\|seqDtime\|setEPS\|setFonts\|setGraphicsEventEnv\|setGraphicsEventHandlers\|setPS\|setQuartzFonts\|setX11Fonts\|svg\|symbolfamilyDefault\|symbolType1support\|terrain\.colors\|tiff\|topo\.colors\|trans3d\|trunc_POSIXt\|Type1Font\|vectorizeConverter\|x11\|X11\|X11\.options\|X11Font\|X11FontError\|X11Fonts\|xfig\|xy\.coords\|xyTable\|xyz\.coords)\s(?=\() scope: meta.function-call.identifier.r captures: 1: support.function.r push: function-call-arguments # methods - match: \b(addNextMethod\|allNames\|Arith\|as\|asMethodDefinition\|assignClassDef\|assignMethodsMetaData\|balanceMethodsList\|bind_activation\|cacheGenericsMetaData\|cacheMetaData\|cacheMethod\|cacheOnAssign\|callGeneric\|callNextMethod\|canCoerce\|cbind\|cbind2\|checkAtAssignment\|checkSlotAssignment\|classesToAM\|classGeneratorFunction\|classLabel\|classMetaName\|className\|coerce\|Compare\|completeClassDefinition\|completeExtends\|completeSubclasses\|Complex\|conformMethod\|defaultDumpName\|defaultPrototype\|dispatchIsInternal\|doPrimitiveMethod\|dumpMethod\|dumpMethods\|el\|elNamed\|empty\.dump\|emptyMethodsList\|envRefInferField\|envRefSetField\|evalOnLoad\|evalqOnLoad\|evalSource\|existsFunction\|existsMethod\|extends\|externalRefMethod\|finalDefaultMethod\|findClass\|findFunction\|findMethod\|findMethods\|findMethodSignatures\|findUnique\|fixPre1\.8\|formalArgs\|fromNextMethod\|functionBody\|generic\.skeleton\|genericForBasic\|getAllSuperClasses\|getClass\|getClassDef\|getClasses\|getDataPart\|getFunction\|getGeneric\|getGenericFromCall\|getGenerics\|getGroup\|getGroupMembers\|getLoadActions\|getMethod\|getMethods\|getMethodsAndAccessors\|getMethodsForDispatch\|getMethodsMetaData\|getPackageName\|getRefClass\|getRefSuperClasses\|getSlots\|getValidity\|hasArg\|hasLoadAction\|hasMethod\|hasMethods\|implicitGeneric\|inBasicFuns\|inferProperties\|inheritedSlotNames\|inheritedSubMethodLists\|initFieldArgs\|initialize\|initMethodDispatch\|initRefFields\|insertClassMethods\|insertMethod\|insertMethodInEmptyList\|insertSource\|installClassMethod\|is\|isBaseFun\|isClass\|isClassDef\|isClassUnion\|isGeneric\|isGrammarSymbol\|isGroup\|isMixin\|isRematched\|isS3Generic\|isSealedClass\|isSealedMethod\|isVirtualClass\|isXS3Class\|kronecker\|languageEl\|linearizeMlist\|listFromMethods\|listFromMlist\|loadMethod\|Logic\|makeClassMethod\|makeClassRepresentation\|makeEnvRefMethods\|makeExtends\|makeGeneric\|makeMethodsList\|makePrototypeFromClassDef\|makeStandardGeneric\|matchDefaults\|matchSignature\|Math\|Math2\|mergeMethods\|metaNameUndo\|method\.skeleton\|MethodAddCoerce\|methodSignatureMatrix\|MethodsList\|MethodsListSelect\|methodsPackageMetaName\|missingArg\|multipleClasses\|new\|newBasic\|newClassRepresentation\|newEmptyObject\|Ops\|outerLabels\|packageSlot\|possibleExtends\|print\.MethodsList\|printClassRepresentation\|printPropertiesList\|prohibitGeneric\|promptClass\|promptMethods\|prototype\|Quote\|rbind\|rbind2\|reconcilePropertiesAndPrototype\|refClassFields\|refClassInformation\|refClassMethods\|refClassPrompt\|refObjectClass\|registerImplicitGenerics\|rematchDefinition\|removeClass\|removeGeneric\|removeMethod\|removeMethods\|representation\|requireMethods\|resetClass\|resetGeneric\|S3Class\|S3forS4Methods\|S3Part\|sealClass\|selectMethod\|selectSuperClasses\|setAs\|setCacheOnAssign\|setClass\|setClassUnion\|setDataPart\|setGeneric\|setGenericImplicit\|setGroupGeneric\|setIs\|setLoadAction\|setLoadActions\|setMethod\|setNames\|setOldClass\|setPackageName\|setPackageSlot\|setPrimitiveMethods\|setRefClass\|setReplaceMethod\|setValidity\|show\|showClass\|showClassMethod\|showDefault\|showExtends\|showExtraSlots\|showMethods\|showMlist\|showRefClassDef\|signature\|SignatureMethod\|sigToEnv\|slot\|slotNames\|slotsFromS3\|substituteDirect\|substituteFunctionArgs\|Summary\|superClassDepth\|superClassMethodName\|tableNames\|testInheritedMethods\|testVirtual\|tryNew\|unRematchDefinition\|useMTable\|validObject\|validSlotNames)\s(?=\() scope: meta.function-call.identifier.r captures: 1: support.function.r push: function-call-arguments # stats - match: 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scope: meta.function-call.identifier.r captures: 1: support.function.r push: function-call-arguments # utils - match: 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scope: meta.function-call.identifier.r captures: 1: support.function.r push: function-call-arguments
Epithelial ovarian carcinoma is the leading cause of death from gynecologic cancer in the US. Approximately 75% of patients present with advanced stage disease, for which the five-year survival rate remains below 30%, whereas the five-year survival rate for stage I disease is 93%. Therefore, it is anticipated that effective methods of early detection of ovarian cancer would substantially reduce overall mortality rates for this disease. Despite much effort, there are currently no reliable procedures for the early detection of ovarian cancer available. [unreadable] [unreadable] In the past decade, a substantial amount of evidence for the occurrence of extensive alterations of DNA methylation patterns in cancer cells has accumulated. We and others have recently shown that these abnormal DNA methylation patterns can be detected in tumor-derived DNA in the serum and plasma of cancer patients. [unreadable] [unreadable] We propose to use a sophisticated automated methylation analysis technology that we have developed, called MethyLight, to screen a large panel of genes to identify markers specific for ovarian cancer, compared to non-neoplastic ovarian tissue. This will allow the correlation of methylated markers in ovarian tumors with clinicopathological features, and with response to chemotherapy and overall survival. Subsequently, we can use the information obtained in this screen of tissue samples to develop markers for the detection of ovarian tumor-derived DNA in the serum of patients with existing or recurring disease. Finally, we propose to use the most promising biomarkers to evaluate the capacity to detect preclinical relapse of disease, as a function of time before clinical diagnosis of relapse.
Scheiner Law Group P.C. 2211 Norfolk Street #735 Houston, TX 77098 Office (713) 783-8998 After Hours Call or Text 713-581-4540 Contact Us Contact our Houston Criminal Lawyers at 713-783-8998 Restoring a sense of normalcy to your life following a criminal case can be difficult. There are often lasting and negative effects. A criminal conviction will leave a permanent stain on your record, one that may affect your ability to get a job, obtain credit, or attend college or graduate school. For prospective clients, if you are unable to reach this office Monday through Friday during normal business hours, you may use this form to contact us. We will get back to you as soon as possible. Please include your e-mail address if you would like a written reply. FREE CASE REVIEW Name Email Phone How can we help? IMPORTANT NOTE: This firm advises its clients not to speak with anyone about their cases. We advise our clients against speaking with friends, witnesses, and especially the police. Further, we advise our clients not to speak with any attorney or person who claims to be “investigating” the incident about which a client is inquiring. Contact Us was last modified: August 3rd, 2017 by Grant Scheiner Scheiner Law Group, P.C. 2211 Norfolk Street #735 Houston, TX 77098 Office (713) 783-8998 After Hours Call or Text 713-581-4540 Español 713-226-9393 More Info Disclaimer The information you obtain at this site is not, nor is it intended to be, legal advice. You should consult a lawyer for individual advice regarding your own situation. The content of this website refers to Texas and federal law only. You should not act on any information in this website without first speaking with an attorney. No attorney-client relationship is created with this firm until we meet with you and expressly agree to take your case.
USCA1 Opinion May 30, 1995 [NOT FOR PUBLICATION] United States Court of Appeals For the First Circuit ____________________ No. 94-2289 PUERTO RICO MARINE MANAGEMENT, INC., Plaintiff, Appellee, v. EMPRESAS MASSO, ET AL., Defendants, Appellants. ____________________ APPEAL FROM THE UNITED STATES DISTRICT COURT FOR THE DISTRICT OF PUERTO RICO [Hon. Hector M. Laffitte, U.S. District Judge] ___________________ ____________________ Before Selya, Circuit Judge, _____________ Coffin, Senior Circuit Judge, ____________________ and Cyr, Circuit Judge. _____________ ____________________ Jose A. Hernandez Mayoral with whom Rafael Hernandez Mayoral was __________________________ ________________________ on brief for appellants. Carlos J. Quilichini with whom Juan Carlos Gorbea was on brief _____________________ ___________________ for appellee. ____________________ ____________________ COFFIN, Senior Circuit Judge. This is an appeal from a _____________________ judgment, following a bench trial, for plaintiff vessel operator, Puerto Rico Marine Management (PRMMI), in its suit to collect freight charges for a deficit of cargo placed under a Time Volume Agreement (TVA) by defendants (collectively, Masso).1 Under the TVA, covering the period from May 1990 to August 1992, Masso agreed to ship a minimum of 500 "trailers" annually from continental United States to Puerto Rico. The complaint alleged that during this period only 410 shipments were booked; the deficit was 590. Applying the appropriate tariff of "$250.00 per container/trailer," the total claimed deficit was $147,500. Masso's response to the complaint was the affirmative defense that PRMMI breached the TVA. In the pre-trial order, submitted to the court by both parties, Masso outlined its defense: the TVA (through its use of ther judges are tempted to resort to "preachy" opinions, issuing admonitions about the future which they and their courts are unlikely to follow up with vigor. An example is the unhappiness of appellate courts with some of the closing arguments to the jury made by overzealous prosecutors. In an otherwise error-free case it is tempting to shake a judicial finger and say, "We shall not in the future permit such conduct." But the next case comes along, with overwhelming evidence of guilt and in the main a fair trial. An appellate court will be reluctant to reverse and will therefore ____________________ 1 Empresas Masso, Inc., Bloques Masso, Inc., Ferreteria Masso, Inc., Caguas Lumber Yard, Inc., Masso Enterprises, Inc. look to see if objection was made to the offending argument, if the judge made an immediate curative instruction, and if in the context of the entire case the remarks were likely to have had any effect. One learns from long and frustrating experience that one reversal is worth a hundred lectures. In such matters as these, affecting the manner in which cases are tried and the rules and standards governing judges and counsel, an appellate court may on occasion rest its decision, not on a constitution, statue or regulation, or even upon case precedents, but upon its own supervisory authority over the agencies and courts within its jurisdiction. It is a power to be used sparingly, but does allow fine tuning not confined to the precise issues raised by a particular case. When a panel of a federal court decides to take this route, it usually circulates its proposed rule to all members of the court for comment and agreement. It is understandable that an attorney in an appellate court is so immersed in her case that her attention has been rivetted on winning a victory. "Victory" is usually translated into the simple alternatives: affirmance or reversal. But the court itself must confront a number of collateral choices having to do with the kind, form, finality, secondary consequences, and timing of decision. Some of these choices will be seen as immensely important to the litigants and their counsel. Some chiefly concern the internal workings of the court. But all are worth some thought on the part of counsel . . . in order to be of help both to themselves and the court. -3- 2. Unfinished business. Before a conference ends, the ___________________ court must reflect on whether decision is the next step. It may be that, before a novel approach is taken, supplemental memoranda should be requested. Or perhaps at oral argument they already have been. Or it may be that, at oral argument, the court has suggested that the parties attempt to settle the case, or that a compromise resolution be explored. And sometimes, when a case involving the same issue is pending before the Supreme Court, the court will simply defer its decision until The Supreme Court acts. 3. Disposition choices. The two options for a final ____________________ decision are, of course, to affirm or reverse. An added subtlety is a decision whether or not to have the mandate (the document that evidences the fact that it the decision is now effective) issue immediately or to allow some time for a petition for certiorari (i.e., a request that the case be accepted for review) __________ to be presented to the Supreme Court of the United States. Decisions that are somewhat less than final are those which remand the case to the trial court. There are many variants: a remand with instructions only to "institute proceedings in accordance with this opinion;" a remand with specific instructions (e.g., in a successful habeas corpus appeal, a remand to the federal district court with instructions to grant the prisoner's freedom unless the state initiates a new trial within ninety days); a remand for clarification of the court's reasoning, or for essential fact finding; a remand with or -4- without a requirement to open the record for additional evidence; and a remand to a different judge. Each one of these possibilities could be fraught with significance for a litigant; an advocate would do well to anticipate these choices and be prepared to give advice to the court. Then there are critical choices as to timing. A basic question is whether a new rule or an extension of existing law should be applicable prospectively or retrospectively. But there are timing questions relating to the issuance of the instant decision. Sometimes the panel (if it is a federal court of appeals) knows that one of the issues is being considered by another panel in another case; some checking with that panel is indicated. The resry, and conceded that a number of lumber shipments had been made for Masso on lo/lo vessels. He did testify that "for a period of time" in the latter part of 1990 there was no ro/ro vessel servicing Jacksonville, and he also stated that at sales meetings, in trying to anticipate revenues, he would review contracts, including Masso's TVA. Unable to give more specific testimony because of the sanctions imposed by the court, he gave his conclusory opinion that PRMMI did not provide MASSO with enough ro/ro service to comply with the TVA. This evidence, even viewed most charitably for defendants on the assumption that only ro/ro's were contemplated by the TVA, might support a finding that to some extent at some time PRMMI did not live up to its undertaking. But it is clear that, contrary to defendants' initial contention, PRMMI did not phase -5- out its ro/ro fleet during the contract period. Two of the three ro/ro vessels remained in service for the duration. It is also clear that, except for one period of time of uncertain length, there was no failure to provide ro/ro service to any port. Generally, the temporary unavailability of a vessel resulted in biweekly rather than weekly service for a post. What is left completely unclear is any basis for assessing the magnitude of any breach on PRMMI's part, to determine if it was sufficient to justify Masso's failure to book more than half of its promised shipments during the two-year period. The record is bereft of data as to dates, ports, cargoes, and substituted arrangements relating to shipments frustrated because of a lack of proper equipment. Moreover, the record contains no evidence of expressed unhappiness, oral or written, over PRMMI's performance; acquiescence and waiver remain distinct possibilities. On all of this, we remind ourselves, defendants bore the burden of both going forward with evidence and the ultimate burden of persuasion. On the record, therefore, we must rule, as a matter of law, that defendants simply failed to support their affirmative defense. AFFIRMED. -6-
Joseph J. Daynes Joseph John Daynes (April 2, 1851 – January 15, 1920) was the first organist at the Salt Lake Tabernacle and for the Mormon Tabernacle Choir. Daynes was born in Norwich, England, to John Daynes and Eliza Miller. The Daynes family later joined The Church of Jesus Christ of Latter-day Saints (LDS Church) and then immigrated to Utah Territory in 1862. Upon their arrival in the Salt Lake Valley, Brigham Young met the group of Latter-day Saints with whom the Daynes family had traveled. Young heard the eleven-year-old Joseph playing the melodeon and declared: "There is our organist for the great Tabernacle organ." This declaration came true in 1867, when Joseph H. Ridges completed the building of the organ in the Salt Lake Tabernacle. Daynes had been sent to study music in New York. Upon the organ's completion, he became the first Tabernacle organist at age sixteen, a position which he held until 1900. Daynes also served as the music conductor of the 20th Ward Choir in Salt Lake City. Daynes came from a very musical family. Though his father, John, was a watchmaker by trade, his hobby was music. The piano which John purchased in England is the instrument Daynes learned to play on. Daynes learned quickly—and largely on his own—and by age six participated in an organ recital. When the Daynes family left England for the United States, they brought several instruments with them, including the melodeon Young heard Daynes playing to entertain the other pioneers. John Daynes continued to develop his love of music and founded Daynes Music in 1862, in Salt Lake City, a company which is still in business today. Joseph Daynes married Mary Jane Sharp on November 18, 1872, in Salt Lake City. They had seven children. Daynes was one of the main editors of the Latter-day Saints' Psalmody. He also wrote the music for many of the hymns of the LDS Church. The 1985 English-language hymnal of the church contains five hymns with music composed by Daynes, while the previous edition of the hymnal contained 27 hymns with music by him. Daynes also wrote several anthems. Among the hymns Daynes composed the music for are "Come Listen to a Prophet's Voice," "Now We'll Sing with One Accord," and "As the Dew from Heaven Distilling," which is the traditional closing hymn for the Tabernacle Choir's weekly Music and the Spoken Word broadcasts. Daynes's son Joseph J. Daynes Jr. served as the first president of the Grant Stake in Salt Lake City. Daynes Jr. was also the president of the Western States Mission of the church, based in Colorado, and was married to one of Wilford Woodruff's daughters. Evan Stephens, who conducted the Mormon Tabernacle Choir for many years while Daynes accompanied them, said of Daynes: "He was, without doubt, one of the greatest organists of his time. In my experience I never heard his equal as an accompanist for the choir and soloists and he was the very best sight reader I ever knew." Notes References Mormon Tabernacle Choir listing of Daynes accomplishments J. Spencer Cornwall. The Story of Our Mormon Hymns. (Salt Lake City: Deseret Book, 1975) p. 240-241 B. H. Roberts. Comprehensive History of the Church of Jesus Christ of Latter-day Saints. (1930, Reprint 1991: Orem, Sonos Publishing) 6:253. Encyclopedia of Mormonism, p. 232. . Daynes Music Company External links Category:1851 births Category:1920 deaths Category:Burials at Salt Lake City Cemetery Category:Editors of Latter Day Saint publications Category:English conductors (music) Category:British male conductors (music) Category:English emigrants to the United States Category:English hymnwriters Category:English Latter Day Saints Category:English organists Category:Male organists Category:English Latter Day Saint hymnwriters Category:Mormon pioneers Category:Mormon Tabernacle Choir organists Category:People from Norwich
Articles such as produce ideally should be packaged in containers which protect the contents against bruising or other damage during shipment and handling. The containers should also present an appealing appearance so that they can be used as retail packages after reaching their final destination, and should be economical as well. One type of container used to package produce is comprised of separate rigid end panels about which a flexible cover sheet is wrapped to form the bottom, side and top panels. The end panels include stacking projections on their upper or lower edge and stacking recesses on their opposite edge. When the containers are stacked, the projections from one container fit into the recesses of the next higher or lower container. The flexible sheet includes slots for receiving the stacking projections and the corners of the end panels. Means are also provided on the end panels for holding the ends of the sheet in place. Typically, the ends of the sheet may overlap to form a fully enclosed container or they may be spaced from each other to provide a partially open top panel. The containers permit ready circulation of air to maintain the produce fresh and they can also serve as retail packages after reaching their final destination. The end panels are typically formed of thick paperboard, pressed board or other readily available economical rigid material, while the flexible cover sheets are typically formed of paperboard of a thickness normally used in the manufacture of carriers from foldable paperboard blanks. Due to strength requirements the thickness of the end panels is typically several times greater than the thickness of the cover sheet. This arrangement requires a separate supply of the relatively expensive end panels which drives up the cost of the containers. In addition, it restricts the application of printing or other indicia to the cover sheet, resulting in plain end panels which prevent the container from having an overall integrated appearance. A main object of the invention is to provide a produce container which makes use of the basic design concept referred to above but is not restricted to an end panel design of the type described. Another object is to provide such a container with strengthened side panels to further improve the ability of the container to resist loading and handling stresses.
He was certainly one of the great players of his generation - but one of the top 5 players of all time? That's debatable. Nonetheless, when asked to name his all-time top 5 in a recent interview with Esporte Pono Final, Romario has included himself. Not only is he included, he's second top - behind only Pele in the rankings. If that seems a tad cocky, just wait until you see the players he's left out. In descending order, here's his top 5... 5. Zinedine Zidane (Image: Getty) 4. Ronaldo 3. Diego Maradona (Image: Mark Leech) 2. Romario (Image: Getty) 1. Pele (Image: mirrorpix) That's a pretty solid list, at first glance. However, when you realise that Romario has left out both Lionel Messi and Cristiano Ronaldo, his inclusion starts to look a little suspect.
Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides. Photoreceptor cells are incessantly bombarded with photons of light, which, along with the cells' high rate of oxygen metabolism, continuously exposes them to elevated levels of toxic reactive oxygen intermediates (ROIs). Vacancy-engineered mixed-valence-state cerium oxide nanoparticles (nanoceria particles) scavenge ROIs. Our data show that nanoceria particles prevent increases in the intracellular concentrations of ROIs in primary cell cultures of rat retina and, in vivo, prevent loss of vision due to light-induced degeneration of photoreceptor cells. These data indicate that the nanoceria particles may be effective in inhibiting the progression of ROI-induced cell death, which is thought to be involved in macular degeneration, retinitis pigmentosa and other blinding diseases, as well as the ROI-induced death of other cell types in diabetes, Alzheimer's disease, atherosclerosis, stroke and so on. The use of nanoceria particles as a direct therapy for multiple diseases represents a novel strategy and suggests that they may represent a unique platform technology.
Tachycardia: an important determinant of coronary risk in hypertension. Heart rate and blood pressure are highly correlated and in large population studies, individuals with high blood pressure tend to have high heart rates. Fast heart rate precedes the development of high blood pressure and serves as an early indicator of coronary heart disease. Not only does the heart rate predict coronary mortality, but also the non-cardiovascular mortality and is, therefore, an overall predictor of longevity. In the Tecumseh Blood Pressure study, we have seen that 37% of all patients with borderline hypertension have the 'hyperkinetic hypertension state', which consists of elevated cardiac output, high heart rate, high sympathetic tone, and decreased parasympathetic tone. In this population, evidence of high heart rate exists in these individuals as children, and persists through early adulthood. This suggests that tachycardia is a reliable marker of high sympathetic tone. High sympathetic tone might be the mechanism whereby heart rate is associated with high insulin, insulin resistance, dyslipidemia, high hematocrit and excess weight. These mechanisms are discussed in details in this review. Tachycardia is a strong risk factor for sudden death and arrythmia. Heart rate, as one of the prime determinants of cardiac work, may contribute to greater cardiac strain. Animal studies have shown that a higher heart rate may be associated with a greater development of atherosclerotic plaque in coronary vasculature. Therefore, heart rate elevation is not merely a sign of underlying pathology, but it may also cause further damage that leads to increased mortality. In the treatment of hypertension, reducing heart rate by pharmacologic and non-pharmacologic measures may have a greater effect on coronary mortality than blood pressure reduction alone.
Q: Is it possible to reuse Connections on Azure Functions when sending Device-to-Cloud messages to IoTHub? I have an Azure IoTHub with thousands of devices registered. These devices communicate through a Telco provider who sends messages through an Azure Storage Queue. This Storage Queue triggers an Azure Function which needs to parse the messages and Send an Event to the IoTHub as below. Currently, we use the Azure IoTHub SDK to create a DeviceClient for each payload and we send the event. Because the DeviceClient represents a device in the IoTHub and is carrying the context of the source of the events, we are having to recreate a device client for each event. This quickly exceeds the threshold of the number of Connections allowed on Azure Functions. We have tried using the IoTHub Output bindings for Azure Functions, but could not get to work and I do not think it would work because we need to make sure that the events get to the IoTHub with the right context (messages are sent by the right device). What's the right way to solve this? Can the connections to the IoTHub be reused? Should we abandon Azure Function in favour of something else? A: After trying a few things, I ended up moving away from using the SDK for pushing messages to IoT Hub. This is because the SDK uses AMQP, and creating a DeviceClient for each payload is not viable. We switched to using HTTPS instead to push the messages to IoT Hub and using HttpClientFactory, we are able to do connection pooling. I thought I would put this here in case someone has the same issue. Here is an example of the Http request to send message to IoT Hub Host: https://<iothubname>.azure-devices.net/devices/<deviceId>/messages/events?api-version=2018-06-30 Authorization: SharedAccessSignature sr=<iothubname>.azure-devices.net&sig=abc123;12344iweoippweruea=iothubowner&se=1570574220 Body: <normal Interval or alarms payloads> // example {"deviceid": "abc", "hello": "world"} Lastly, thanks @kgalic for the answer but your suggestion would not work. This is not pure B2B integration. Our implementation have to allow for both devices connecting directly to the IoT Hub and devices connecting through the Telco. This is why every device needs to have its own identity and digital twin.
/* * Copyright (C) 1995-1997 Olaf Kirch <okir@monad.swb.de> / #ifndef LINUX_NFSD_VFS_H #define LINUX_NFSD_VFS_H #include "nfsfh.h" / * Flags for nfsd_permission / #define NFSD_MAY_NOP 0 #define NFSD_MAY_EXEC 1 / == MAY_EXEC / #define NFSD_MAY_WRITE 2 / == MAY_WRITE / #define NFSD_MAY_READ 4 / == MAY_READ / #define NFSD_MAY_SATTR 8 #define NFSD_MAY_TRUNC 16 #define NFSD_MAY_LOCK 32 #define NFSD_MAY_MASK 63 / extra hints to permission and open routines: / #define NFSD_MAY_OWNER_OVERRIDE 64 #define NFSD_MAY_LOCAL_ACCESS 128 / IRIX doing local access check on device special file/ #define NFSD_MAY_BYPASS_GSS_ON_ROOT 256 #define NFSD_MAY_NOT_BREAK_LEASE 512 #define NFSD_MAY_BYPASS_GSS 1024 #define NFSD_MAY_READ_IF_EXEC 2048 #define NFSD_MAY_CREATE (NFSD_MAY_EXEC\|NFSD_MAY_WRITE) #define NFSD_MAY_REMOVE (NFSD_MAY_EXEC\|NFSD_MAY_WRITE\|NFSD_MAY_TRUNC) / * Callback function for readdir / typedef int (nfsd_dirop_t)(struct inode , struct dentry , int, int); /* nfsd/vfs.c / int fh_lock_parent(struct svc_fh , struct dentry ); int nfsd_racache_init(int); void nfsd_racache_shutdown(void); int nfsd_cross_mnt(struct svc_rqst rqstp, struct dentry dpp, struct svc_export expp); __be32 nfsd_lookup(struct svc_rqst , struct svc_fh , const char , unsigned int, struct svc_fh ); __be32 nfsd_lookup_dentry(struct svc_rqst , struct svc_fh , const char , unsigned int, struct svc_export , struct dentry ); __be32 nfsd_setattr(struct svc_rqst , struct svc_fh , struct iattr , int, time_t); int nfsd_mountpoint(struct dentry , struct svc_export ); #ifdef CONFIG_NFSD_V4 __be32 nfsd4_set_nfs4_acl(struct svc_rqst , struct svc_fh , struct nfs4_acl ); int nfsd4_get_nfs4_acl(struct svc_rqst , struct dentry , struct nfs4_acl ); #endif / CONFIG_NFSD_V4 / __be32 nfsd_create(struct svc_rqst , struct svc_fh , char name, int len, struct iattr attrs, int type, dev_t rdev, struct svc_fh res); #ifdef CONFIG_NFSD_V3 __be32 nfsd_access(struct svc_rqst , struct svc_fh , u32 , u32 ); __be32 do_nfsd_create(struct svc_rqst , struct svc_fh , char name, int len, struct iattr attrs, struct svc_fh res, int createmode, u32 verifier, int truncp, int created); __be32 nfsd_commit(struct svc_rqst , struct svc_fh , loff_t, unsigned long); #endif /* CONFIG_NFSD_V3 / __be32 nfsd_open(struct svc_rqst , struct svc_fh , int, int, struct file ); void nfsd_close(struct file ); __be32 nfsd_read(struct svc_rqst , struct svc_fh , loff_t, struct kvec , int, unsigned long ); __be32 nfsd_read_file(struct svc_rqst , struct svc_fh , struct file , loff_t, struct kvec , int, unsigned long ); __be32 nfsd_write(struct svc_rqst , struct svc_fh ,struct file , loff_t, struct kvec ,int, unsigned long , int ); __be32 nfsd_readlink(struct svc_rqst , struct svc_fh , char , int ); __be32 nfsd_symlink(struct svc_rqst , struct svc_fh , char name, int len, char path, int plen, struct svc_fh res, struct iattr ); __be32 nfsd_link(struct svc_rqst , struct svc_fh , char , int, struct svc_fh ); __be32 nfsd_rename(struct svc_rqst , struct svc_fh , char , int, struct svc_fh , char , int); __be32 nfsd_remove(struct svc_rqst , struct svc_fh , char , int); __be32 nfsd_unlink(struct svc_rqst , struct svc_fh , int type, char name, int len); int nfsd_truncate(struct svc_rqst , struct svc_fh , unsigned long size); __be32 nfsd_readdir(struct svc_rqst , struct svc_fh , loff_t , struct readdir_cd , filldir_t); __be32 nfsd_statfs(struct svc_rqst , struct svc_fh , struct kstatfs , int access); int nfsd_notify_change(struct inode , struct iattr ); __be32 nfsd_permission(struct svc_rqst , struct svc_export , struct dentry , int); int nfsd_sync_dir(struct dentry dp); #if defined(CONFIG_NFSD_V2_ACL) \|\| defined(CONFIG_NFSD_V3_ACL) struct posix_acl nfsd_get_posix_acl(struct svc_fh , int); int nfsd_set_posix_acl(struct svc_fh , int, struct posix_acl ); #endif #endif / LINUX_NFSD_VFS_H */
Q: Changes in org-agenda-custom-commands? I had set up an Agenda view for showing today's tasks and TODOs with tags "UPCOMING" or "PROJECT": (setq org-agenda-custom-commands '(("w" "Agenda + TODOs" ((agenda "" ((org-agenda-ndays 1))) (tags-todo "UPCOMING") (tags-todo "PROJECT"))))) Now, after updating org-mode yesterday, it still works fine, but instead of showing just today's tasks, it shows the entire week. Any idea what might have caused this? A: Depending on which version you upgraded to, you might find that org-agenda-ndays does not exist any longer. Try this: (setq org-agenda-custom-commands '(("w" "Agenda + TODOs" ((agenda "" ((org-agenda-span (quote day)))) (tags-todo "UPCOMING") (tags-todo "PROJECT"))))) instead.
The P50 Specialized Population Research Center described in this proposal is comprised of five research projects and four core laboratories that will perform research designed to achieve a broad understanding of testes and their two major products, germ cells and steroid hormones. The biology of newly and recently identified Sertoli cell proteins will provide the basis for evaluating seminiferous tubular function and for isolating and sequencing germ cell proteins that regulate Sertoli cells. A detailed understanding of the Sertoli cell product, androgen-binding protein (ABP), will be derived from an analysis of how individual structural changes in this protein alter its function; following alterations in the ABP cDNA, mutant ABP produced in vitro will be compared with native ABP so that the structure of this binding protein can be related to its ability to bind and activate androgen-responsive cells. Studies of the promoter regions of the B-glucuronidase and KAP genes will identify regions of interaction with androgen receptor and other transcription factors; these experiments will provide an understanding of how androgen stimulates specific genes in selected tissues. Parallel studies of the clusterin gene promoter will demonstrate how cAMP suppresses accumulation of this mRNA in Leydig and Sertoli cells; unlike the well-characterized process by which cAMP stimulates selected genes, the suppressive effect of this intracellular modulator on transcription has not been elucidated.
Remember the excitement over Peru? In the previous decade, its main stock index outperformed every other equity market in the world. Its copper-fueled economy seemed unstoppable. Headlines enthused over an emerging middle class spending money in shopping malls and Lima’s hot new restaurants and night clubs. But the crash in commodities in the current decade put paid to all of that. Foreign companies once lauded for helping build roads, schools and health clinics became the enemy. Deadly protests, the likes of which had not been seen since the military took power in the 1960s, flared up against one Chinese mining venture for failing to create more jobs and protect the environment. The heavy-handed military and police response provided further deterrence to once-bullish investors. Now, it seems, good times may be returning to the Andes. This year Peru’s equity market index is once again the world’s best performing, with a rally of over 34% so far in 2016. With the country in the midst of presidential elections, the lofty stock market performance belies the political tensions. Both presidential contenders are pro-business and free markets. Keiko Fujimori is the conservative daughter of a jailed former authoritarian president. Pedro Pablo Kuczynski is a centrist ex-World Bank economist. - Advertisement - Peru’s stock market rallied the most since 2008 as the two candidates defeated leftist Veronika Mendoza in the first round of voting earlier this month. Runoffs for the presidential race will take place in June. But there’s another reason for taking a look at Peru. It’s harvest time. Not for farmers – but investors. “Peru is a case of making hay with the grass that you’ve sown a few years ago,” Kieran Curtis, a fund manager overseeing $1.3 billion of emerging market debt assets for Standard Life, says on this week’s Emerging Opportunities show. “A few years ago it was all about investment, and then the investment began to slow as the projects being funded were nearing completion. That meant a drop in economic growth, and somewhat of a change in market sentiment around Peru. But now these projects are actually completed. They’re starting to produce.” Most of the production is in copper, Peru’s largest export. By the end of 2017, those projects will increase Peru’s production by almost 90% when compared to the third quarter of 2015. Such a big jump in exports can normally be expected to drive returns for foreign buyers of local currency. That adds to the allure of domestic bonds, with 10-year yields having reached 7.5% this year, while inflation has been around a third of that level at 2.5%, says Curtis, who holds an outsize amount of Peru’s bonds. Here are some of Curtis’s other top picks, along with countries where he recommends caution: Indonesia: Changes to coalitions in Congress last year gave President Joko Widodo much more strength to push through his agenda. We’ve seen a fall in inflation, which has certainly helped market sentiment and enabled some rate cuts from Bank Indonesia. But we’ve also seen the government expedite infrastructure spending that Indonesia has needed badly for a long time. We got our first evidence of this in the first quarter, when government capital expenditure was actually up 300% from the prior year. Dominican Republic: We can get very high yields on domestic assets, in the region of about 10%. And this is for a country that has quite low debt. Government debt is in the range of 30 percentage-points of GDP, and inflation is in the very low single digits. The Dominican Republic has been enjoying very strong growth recently, because there’s been some heavy investment in the not too distant past. The country is enjoying the benefits of investment in tourism. This has been growing strongly because capacity has been added in cruise ship terminals and in hotels. Then there’s also gold mining. One of the largest gold projects came online a couple of years ago, so that’s driven export revenues as well. Turkey: There are positives and negatives being created on a daily basis in Turkey. Potentially, one positive is the Cyprus peace deal, which many people expect might be achieved by year-end. But really, what concerns us is the structure of financing for the economy. The government has been very careful with its own debt and has paid down as much debt as it can, and has been very fiscally conservative. But the private sector has borrowed a lot, and actually, if you look at the growth in credit as a share of GDP – the change in that ratio – Turkey is second only to China in the emerging world. So, this has basically led to Turkey being probably the most vulnerable emerging market to, say, a change in Fed policy to a more aggressive stance, changes in liquidity and foreign-currency funding markets. Listen to the show here
For Thai Tok Sen Massage practitioners or therapists who want to buy Tok Sen tools and equipment in the USA, the obvious choice would be to buy with an online shop – Tok Sen supplies are rather special Thai massage tools and of course rarely to be found around the corner of your street in the US. Tok Sen is a so-called Lanna Folk Healing modality, with training, treatments and tool offerings mainly in the Chiang Mai area (Northern Thailand), and even in Thailand the tools are quite difficult to obtain elsewhere. In Western countries, the healing Tok Sen Massage modality is also called Thai Hammer Massage. Having said that, in this article we’re going to take look at some of the suppliers and their variety of Tok Sen tools offerings on Amazon. TraditionalBodywork.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com and Amazon.co.uk Give Or Buy Give Or Buy is a Thai E-Commerce Company and located in Chiangmai, Thailand. The company sells many other Northern Lanna Thai products also, like typical clothing such as so-called Thai Fisherman’s Pants, and balms, handicrafts, and so on. The Tok Sen set displayed below is produced by the company Thailand spa product. Specifically made for Tok Sen treatments: size H 8.5 Inches, 3 pieces in a pack, made from Red Wood, high quality durable massage tool set. The tool set below is one of their Tok Sen sets made in Thailand and includes 2 side chisels + 2 prongs + percussion stick + a bi-dent two-pronged stick. The size of the tools is about 9 inch and made from Ironwood, handcrafted. Another example of a Tok sen Massage set offered by the Kingdom Of Smile: UnseenThailand Warehouse UnseenThailand Warehouse offers a variety of Thai handicrafts and decorations, including Tok Sen tools or Spirit Houses, many of wood. Additionally, the company also provides Gua-sha scraping sets, Thai pillows, coasters, Herbal Compress Massage Balls, among other things. The company runs its own brand, but sells other Thai brands also. The Tok Sen set below has a size of approx. 8.5 Inches, comes with 3 pieces in a pack, and is produced from Red Teak Wood. Ajarn Sompong Prapharat Ajarn teacher Sompong from Waulai Thaimassage in Chiang Mai is specialized in Herball Ball Compress Massage courses and treatments, but also offers Reusi Dat Ton and Tok Sen massage trainings. Interesting enough he offers a Tok Sen massage set to be purchased on Amazon. The specialty here is that it’s a tool set with a hand written mantra on it and blessed by Arjarn Sompong in the real tradition of a Tok Sen Master-Student relationship. Newsletter Join our Newsletter Name* Email* After submitting this form you will receive an email. Please follow instructions therein to confirm your subscription request. Check your spam / junk mail folder if you don't receive an email or verify the email address you supplied to us.
There is simply no need to charge prices like that,Im not interested in an argument about declining CD sales, pirating, market forces etc its too much, as there is little doubt that this will be a final farewell, so people will feel obliged to shell out or miss out I find it all a bit tasteless to be frank, you have NP quoted in the last few days about the uncertainty of going out again due to his daughter and family, motivations etc, then someone in management has quoted some revenue projections, and pictures of an R40 drumkit miraculously appear. They may indeed have once been a good band, and I have no issue with people clinging on to that fact. spot on Jonners, that is why I posted what I did about NP and him feeling guilty about leaving his kid/touring Having said that, I will go and see them one more time if they come across the pond, might even stalk them 2-3 gigs. If they don´t show up, I am OK with that tbh. Im not trying to piss the avid fans off, not my style these days, if they want to see them and pay the prices they will, my views are unlikely to change that But for me I think it is extremely cynical, and dare I say greedy. (not quite as greedy as Priest doing the Epitaph farewell tour, then touring again now however!!!) There will be lifetime, avid fans (like many of the good folk on here) who simply cant afford to see the band this time round, or sit in seats that they would like, and deserve for showing 40 years of loyalty. There will be dads, and mums, who probably would love to take their sons/daughters to see their favourite band and show them what they have banged on about for years and years, but wont be able to afford to.And there will be the really avid fans, who go to a few shows/stalk, and simply wont be able to. And obviously this will impact further on the band, as by all accounts a large proportion of tickets are sold to people who go to multiple gigs.The management have rather cynically realised that the vast majority of fans of the band are middle aged/older, who are more likely to have the expendable income to afford such luxuries as $400 seats. Getting front row tickets shouldn't be about who has the biggest wallet or which mobile phone operator they subscribe to, its about who gets up earliest, queues overnight in a sleeping bad, begs/borrows/steals favours, scours the websites and hangs on the phone at 8:59 am ready for the pre sale. Yes the band want and need to earn, but the genuine fans who want and deserve those front 20 rows because they have been in the front 20 rows for 40 years, and bought the album on release day for 40 years, should not have to spend $400 for the privilege. Fvck me that is making me angry!!!!!!!!!!! Seems odd that I am moaning on behalf of others when its not affecting me, but it is affecting me, as its putting a very sour taste in my mouth indeed. unfortunately in their latter years, which will be freshest in the memory, the band strike me more as a company/PLC, than a group of artists, and it makes me feel really disappointed. I missed the Brum gig on the last tour, but was more disappointed at missing the social than the gig. Getting front row tickets shouldn't be about who has the biggest wallet or which mobile phone operator they subscribe to, its about who gets up earliest, queues overnight in a sleeping bad, begs/borrows/steals favours, scours the websites and hangs on the phone at 8:59 am ready for the pre sale. Yes the band want and need to earn, but the genuine fans who want and deserve those front 20 rows because they have been in the front 20 rows for 40 years, and bought the album on release day for 40 years, should not have to spend $400 for the privilege. Even the most slavish nu-Rush fanbois - like me - have to agree with that. Well put, Jonners. My first ever Rush gig (this isn't a competition now by the way) was NEC, 1988, and I had to beg my mum to get me the ticket on her credit card, I think it was £10I was about 3 or 4 rows back, Alex side Not sure my mother would be quite so happy shelling out $400 for that ticket...... Im dying for someone to mention inflation or drop in album sales figures Yes I paid a crisp tenner for a ticket at the SECC on the HYF tour.Sorted a spot down the front (all standing) by queuing from around 4pm. Ended up about half-way back after a few numbers due to the melee.... I'd rather reluctantly pay say £30 and sit in the car park next to Karl Beaston, but no way would I pay the silly amounts being bandied about for the privilege of being in the first 14 rows or so - I've been there and done that for far less money when they were a better band than they are today. RTB was better. Saw the tour advertised in the Saturday Evening Times, turned up at opening time at Virgin records on the Monday morning (expected a big queue, but there was none) and grabbed a load of tickets for the 6th row centre. £13.50 each I think they were Prevaricated over this for a few days and have decided I won't be doing this tour. Main reason - I have many other things I'd rather spend a couple of grand on at present. Secondary reasons: 1. I'm going to the Tombstone All Dayer at the Star & Garter in March, and Riff Fest in Bolton in August. On both days I will see at least six bands I currently worship. Entry is £15 for the former, free for the latter. Beer prices will be cheap. I will get to not just watch all the bands up close and personal, but hang out with them throughout the day. Travel costs will be minimal. I won't have to queue for a piss. I will know most of the people in the audience. I will have an absolute riot and will struggle to spend £100 each day. That, presently, is how I like to watch gigs. I can't get excited about an arena show at the moment, especially not at that price. I will miss the fun of traveling with friends and meeting up with them before and after the gigs, but as I've done that with Rush 32 times I don't feel hard done by. Most of the people going over to the States I can see in this country at a convention, in a bar, at a venue, or at Chez Hard. 2. Whilst the "rumour" allegedly eminating from Anthem is there won't be a European tour, they've said that twice before since R30 (including to me when I was still a fanboi and talking to Pegi and Anna). If the festival bods offer them decent money for a string of European festivals they will come here. Its all about the bottom line. I'm quite content seeing them here next year if they come. If they don't then I'll always remember the 5 or 6 shows of the 30 at which I was sober and have decent recall.
// Copyright (C) 2004-2019 Free Software Foundation, Inc. // // This file is part of the GNU ISO C++ Library. This library is free // software; you can redistribute it and/or modify it under the // terms of the GNU General Public License as published by the // Free Software Foundation; either version 3, or (at your option) // any later version. // This library is distributed in the hope that it will be useful, // but WITHOUT ANY WARRANTY; without even the implied warranty of // MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the // GNU General Public License for more details. // You should have received a copy of the GNU General Public License along // with this library; see the file COPYING3. If not see // <http://www.gnu.org/licenses/>. #include <istream> #include <streambuf> #include <sstream> #include <testsuite_hooks.h> #include <testsuite_io.h> using namespace std; void test01() { __gnu_test::fail_wstreambuf bib; wistream stream(&bib); stream.exceptions(ios_base::badbit); try { stream.tellg(); VERIFY( false ); } catch (const __gnu_test::positioning_error&) { // stream should set badbit and rethrow facet_error. VERIFY( stream.bad() ); VERIFY( (stream.rdstate() & ios_base::failbit) == 0 ); VERIFY( !stream.eof() ); } catch (...) { VERIFY(false); } } // libstdc++/9546 int main() { test01(); return 0; }
Announcements Call for Papers Authors are encouraged to submit complete, unpublished, original works that are not under review in any other journals. The scopes of the journal include, but are not limited to, the following fields: Gene structure, expression, replication, and recombination in both eukaryotic and prokaryotic organisms Structure, function, chemistry, and in vivo modification and processing of proteins, nucleic acids, and other biologically important macromolecules Genetics, structure, and growth cycles of viruses and bacteriophages Proteins, nucleic acids, and other biologically important macromolecules research methods We are calling for submission of papers. Please find the journal’s profile at: http://jmbr.ccsenet.org and submit your manuscripts online. If you have any questions, please contact with the editor at: jmbr@ccsenet.org It is appreciated if you could share this information with your colleagues and associates. Thank you. To make sure that you can receive messages from us, please add the 'ccsenet.org' domain to your e-mail 'safe list'. If you do not receive e-mail in your 'inbox', check your 'bulk mail' or 'junk mail' folders.
Wikipedia boss Jimmy Wales to create Facebook competitor? At a gathering of about 100 of some of South Africa’s top geeks on Tuesday night, Wikipedia founder Jimmy Wales revealed what he said were some of the “first screenshots” of his new project on search. But a screenshot that… At a gathering of about 100 of some of South Africa’s top geeks on Tuesday night, Wikipedia founder Jimmy Wales revealed what he said were some of the “first screenshots” of his new project on search. But a screenshot that Wales briefly showed us looked very much like a Facebook profile page, than a search page. In fact it looked pretty much identical to a Facebook profile page. Could this mean Wales is developing a social networking, Facebook competitor too? Could it be some kind of search/social networking hybrid? [UPDATE: Terrence Russell of Wired woke up Jimmy Wales in the early hours of the morning in Bangkok to respond to the speculation.More here.] Described as “Google’s worst nightmare”, Wales said the main “failing” of search engines out there like Google was that they were secretive about the way they ranked search results. In stark contrast to the Open Source movement, these search engines kept information about their algorithms and code close to their chest. “It’s not a healthy thing that power is in the hands of a couple of companies… the information needs to be out there in the public and people involved,” he told the gathering in Johannesburg. His angle is to take on the Googles of this world by making his new search project a collaborative one much like that of Wikipedia. It’s the third time Wales has been to South Africa this year to talk about his projects and work with local communities. Wales’ new projects are being created by a new company, Wikia. The company has been the subject of quite a bit of hype and speculation in recent times. Wikia is a separate organisation to Wikipedia and aims to take the wiki concept to every other kind of work, book, or community projects that people might build. It also aims to extend the Wikipedia model beyond just nonprofit, educational and research communities. The event that Wales’ spoke at in Johannesburg was part of the new iCommons “Innovation Series” at which I also had the privilege of speaking at just before Wales. The next Innovation Series will feature the COO of Second Life, Cory Ondrejka. Congratulations to Heather Ford and Kerryn Mckay from Creative Commons South Africa who pulled this awesome event off. South African languages still small on Wikipedia Wales said the biggest South African language, excluding English, was Afrikaans with only 8 000 entries. The other South African languages were small with a mere 107 entries in Zulu or 78 posts in Xhosa. Wikipedia facts & stats, 2007 Wales said that by the end of 2007 there were now more than 2-million Wikipedia articles in english now, but that this is less than 1/3 of the wikipedia content. German and French are two big growing languages with more than 500,000 articles each. Wikipedia spent around US$1-millon last year, and will spend about $2,3-million this year. Most of this comes from small donations and is a tiny amount of money if you think of the influence Wikipedia has on the world. Wales says that according to Alexa, Wikipedia is now the 8th most popular website in the world. Even in countries like Iran, Wikipedia is the 14th most popular site. Despite Wikipedia being one of the world’s top ten biggest websites, it only has 10 fulltime positions, with most of the work done by volunteers all around the world. […] Matthew Buckland out of South Africa has an interesting recap of a presentation by Jimmy Wales last evening. In his recap, Matthew wonders if Wales is planning a competitor to Facebook based on the slides that were shown. The slides were supposed to be about a new search product but Buckland saw it another way. He notes, "the screenshot that Wales briefly showed the audience looked very much like a Facebook profile page, than a search page. In fact it looked pretty much identical to a Facebook profile page. Could this mean Wales is developing a social networking, Facebook competitor too? Could it be some kind of search/social networking hybrid?" […]
Q: How to use an array of data and a for loop to instantiate objects? I have two arrays one with data var elements = [["1","a",1],["2","b",2],["3","c",3],["4","d",4],["5","e",5]]; And another one with names of the objects which I want to create using data above. var names =["a1","a2","a3","a4","a5"]; This is the prototype class var Video = function(title,uploader,seconds){ this.title = title; this.uploader = uploader; this.seconds = seconds; } I expect to get: a1 which will have values: title:"1",uploader:"a",seconds:1 a2 with values: title:"2",uploader:"b",seconds:2 Same with rest. Or is maybe is there other way to complete task below ? Use an array of data and a for loop to instantiate 5 Video objects. A: function Video(title, uploader, seconds) { this.title = title; this.uploader = uploader; this.seconds = seconds; } var elements = [["1","a",1],["2","b",2],["3","c",3],["4","d",4],["5","e",5]]; var names =["a1","a2","a3","a4","a5"]; // create instances var videos = elements.map(data => new Video(...data)); // add them to hashmap var result = names.reduce((acc, current, index) => { acc[current] = videos[index]; return acc; }, {}); console.log(result);
Brian's Story Prompt, Knowlegable Attention to Minor Chest Pains Averts Disaster Brian Sean McNeely was born on St. Patrick’s Day and has always joked that he’s a leprechaun with a happy-go-lucky demeanor. He certainly had the luck of the Irish on his side on January 27. McNeely experienced an aortic dissection, a rare and serious condition that comes on suddenly, often with no previous risk factors or history of heart disease. Dr. Bryon Boulton, a cardiovascular surgeon with Carolina Cardiovascular Surgical Associates explains, “The wall of an artery has three layers – an aortic dissection occurs when a tear in the inner two layers forces the layers apart and allows blood to flow within the vessel’s walls. It’s a major, life-threatening emergency. Approximately 60 to 70 percent of patients won’t survive without immediate surgical intervention depending on the location of the dissection.” “I woke up and just didn’t feel right, but the pain was so unremarkable that I almost went back to sleep.” McNeely describes the “pain” as a toothpick running through the center of his chest and back through his shoulder blades. It was so minor, he almost wouldn’t describe it as pain. In fact, he drove himself to the WakeMed Brier Creek Healthplex Emergency Department where he was promptly evaluated with no sign of heart attack. Per protocol, McNeely was transferred to the WakeMed Raleigh Campus Chest Pain Unit for further evaluation. Initial testing pointed to a simple infection of the lining around the heart, but to confirm the diagnosis, cardiologist Dr. Charles Mangano of WakeMed Heart & Vascular Physicians ordered a CT scan and an echocardiogram and instead found an aortic dissection. “This is not a common condition, so it’s often misdiagnosed,” explains Dr. Mangano. “We often call it the Great Masquerader, because it can present as chest, shoulder or back pain and can mimic a heart attack, a blood clot in the lung, pericarditis, or even a pulled muscle. Early diagnosis and treatment are the keys to survival.” “Once my results came back, things got very quiet and started moving quickly,” Mc- Neely recalls. “The next thing I knew, I had a heart surgeon in front of me saying, ‘We need to talk.’ Dr. Boulton told me I had experienced something called an aortic dissection, and I immediately remembered John Ritter. I looked at Dr. Boulton with disbelief and said, ‘Like John Ritter?! But, he died!’ That was when I realized the seriousness of my condition, and I was off to surgery before I knew it.” The surgery required removing part of McNeely’s aorta and replacing it with a synthetic graft. It lasted nearly 13 hours. Dr. Boulton explains, “While this condition affects less than one percent of the total population, it is seen on a fairly routine basis at WakeMed, and we have teams in place 24/7 to diagnose and treat emergencies. In this case, it was 8 p.m. on a Sunday night, and our team was immediately ready, prepping for surgery.” “I was in the right place at the right time,” explains McNeely. “There aren’t many places with a top-notch cardiothoracic surgeon like Dr. Boulton and such a phenomenal and thorough cardiologist as Dr. Mangano. I feel very blessed that I chose WakeMed that day. I have never been this passionate about any organization, any group of doctors, nurses and support staff as I am about WakeMed.” Today, McNeely is back to work and living his life with a renewed sense of enthusiasm. He has lost over 75 pounds and says he’ll continue to lose weight by eating less and taking care of himself. He takes medication to keep his blood pressure below the normal minimum because high blood pressure is a risk factor for aortic dissection. “I just hope my experience can serve as a lesson to others to LISTEN to your body,” concludes McNeely. “If I had gone back to sleep and ignored what seemed like pretty unremarkable symptoms, I probably wouldn’t be here today.” As a single dad with four young children – two sets of twins, ages 9 and 12, he doesn’t have much downtime. “I’m convinced part of the reason I’m still here is to care for my kids. They need me and I need them.”
Is there any relationship between toxoplasma infection and reactive arthritis? The diagnosis of reactive arthritis is a challenging clinical problem in daily practice. Although there are many triggering infectious agents for reactive arthritis, Toxoplasmosis, a worldwide parasitic infection has not been reported. We investigated the serologic evidence of Toxoplasma gondii ( T. gondii ) infection in patients with newly diagnosed reactive arthritis after six weeks of the onset of the first symptom but no demonstrable triggering agent for reactive arthritis. Clinical controlled study. We screened serologically the serum toxoplasma IgM and IgG antibody (Ab) titers which revealed toxoplasma infection in 50 patients with reactive arthritis (40 female, 10 men) and no demonstrable triggering agent and control subjects (32 female, 8 male). SPSS 10.0 software package program was used. The mean age of the patients and controls was similar (41.3+/- 12.0 vs. 39.6+/-11.8 years) respectively. The prevalence of IgG Ab titers of T. gondii in patients and controls were found to be 52% and 47.5%, respectively. Mean serum Toxoplasma IgG Ab levels were found to be 16.5+/-14.5 IU/ml, and 16.9+/-13.8 IU/ml in patients and control subjects respectively ( P> 0.05). We did not find any Toxoplasma IgM Ab titer demonstrating the acute or sub-acute infection in the serum of patients or controls. Although past Toxoplasma infection was prevalent in both groups, we did not find any subject with acute Toxoplasma infection in patients with newly diagnosed reactive arthritis and healthy controls. Despite the fact that our study group was small, we suggest that T. gondii does not seem to be a triggering agent for reactive arthritis and past infection may be a coincidental finding.
On April 2nd, 2011, a team of perplexed students, gardeners, and community members gathered with shovels and rakes in hand at the base of Wellesley College’s observatory telescopes pondering the forest of purple, orange, and green stakes poking up from a snow-covered meadow. Mother Nature pulled an April Fools prank of dumping 3” of snow on the site of the Edible Ecosystem Teaching Garden (EETG) for the first morning of our weekend-long implementation workshop. This did not chill the spirits of those who had come to help Kristina Jones, director of the College’s Botanic Gardens, and our design team, as we began planting this experiment in applied ecology. We shoveled snow, grubbed, and sheet mulched patches outlined by wooden stakes, and explained that each bed was designed as a food-producing, low-maintenance analog of natural ecosystems. By the end of the weekend, we had nearly completed planting the 9,300 square foot Nut Grove, first of the eight habitats within the EETG. After one year, plants overtake woodchips in the Wellesley’s Edible Ecosystem Teaching Garden. This spring, during a hot, sunny workday with the some of the Wellesley College Botanical Garden’s summer interns, we were pleased to see that the vast seas of woodchips which dominated the character of the Garden even last fall are now carpeted in a mantle of nutrient accumulating, beneficial insect attracting, colorful, and tasty herbaceous perennials punctuated by small but healthy woody plants. But, alas, not all has gone as planned. Expansive opportunistic species that we sought to suppress have found chinks in sheet mulch while some promising species we planted did not survive the winter. As we move into Year Two of a 5-7 year establishment plan, we’d like to share the harvest of learning that EETG’s polycultures have yielded since our first slushy implementation day. Managing Competition and Directing Succession The spirit of this project, the qualities of the site, and the available resources made setting the successional clock back to zero using conventional disturbance techniques such as herbicide or tillage both impractical and undesirable. However the dominance of several expansive species like crown vetch, various brambles, spurge, and quack grass within the existing plant community would likely limit the ultimate diversity of useful groundcovers in the designed communities. Therefore we are trialing several techniques to manage succession as we nudge this former meadow toward a diversity of horizon habitats. Each technique, including Instant Succession, Nuclei that Merge, and Insertion Plantings, is intended to minimize long-term maintenance requirements while maximizing the garden’s performance. Instant succession involves simultaneously planting the species intended to dominate the habitat at the successional horizon (say, 50 years from now), as well as all the plants intended to dominate in earlier stages of succession. The idea is to plant them all at once, and then “just add water”—an instant succession! Ideally, succession would then simply proceed apace, resulting in the proposed horizon habitat in about the number of years one intended. One large bed at the eastern edge of the Nut Grove exemplifies this approach. This bed now contains young shrubs and trees that will come to dominate the overstory of this future nut and fruit thicket. However, since the woodies are small, the bed is now dominated by sun-loving herbaceous species. We intend these plants to cover the ground, outcompete weeds, improve the soil, attract beneficial organisms, reduce herbivory of the woodies by deer until the woodies are well established, and provide some food, while requiring minimal care ONCE ESTABLISHED! Polyculture action: Chives and dwarf comfrey blossoms attract beneficial insects and can confuse predatory herbivores with their strong scent. Astragalus acts as vigorous groundcover while also fixing nitrogen. Over time, the ‘main crop’ plants like Jostaberry (far left) will come to dominate these patches. We have used the Nuclei that Merge technique to establish the majority of woody plants in the Nut Grove. Since the nut grove is so large and our budget and labor force are relatively small, we avoid disturbing large areas of soil that would require weeding and erosion control. The Nuclei that Merge strategy involves disturbing a small circular patch (size depends upon the weediness of the existing species at each planting location), planting a single tree or shrub in the center of the circle, sheet mulching the disturbed zone with cardboard and wood chips, and then planting groundcover polycultures through the sheet mulch. We intended to surround each disturbed circle with a 4-foot wide black plastic mulch “donut” to kill weeds and prepare the space for the nucleus of groundcovers to expand, but we did not do this the first year due to labor and budget limitations. Mulch donuts (20-year weed barrier) protect nuclei-that-merge plantings like this Hazelnut, mint, astragalus, and barren strawberry polyculture from weed intrusion during establishment. Later, when the nucleus is strong, the plastic mulch will be removed and the weed-free space planted in useful ground covers (5/30/12). A perspective shot of the nuclei-that-merge reveals the pattern of the plantings. Insertion Plantings was the name we gave to species planted in areas where the existing plant community was dominated by desirable species, like a large patch of low-bush (V. angustifolium) and hillside blueberries (V. palladium), and we sought to diversify the patch yields with a minimum of disturbance. The four species planted in this manner (Senguin chestnut, Chinkapin hybrid, European filbert, and American Plum) are growing acceptably but may have benefited from fertility supplements. Performance of Species and Polycultures In natural communities, interspecies interaction can be mutually beneficial, like the relationship between some fungi and plant roots in the form of mycorrhizae. Among the many ideas embodied in the EETG is an attempt to design mixed patches of herbaceous and woody plants that maximize positive interactions while minimizing competition and predation. Within these experimental polycultures we expected to see some plants acting as nurse species by providing nutrients and minimizing ‘weed pressure’. Other plants might support heavier yields by attracting pollinators, while still others might hide long-term crop plants like hazelnuts from herbivores and other pests. During our spring visit it was very satisfying to sit and watch the bees, wasps, and flies foraging among the chives and yarrow which have done a banner job of taking and holding ground, and attracting these early beneficial insects. Astragalus glycyphyllos looks to be a great ground cover polyculture component, though it is a challenge to distinguish it from our main herbaceous rival, crown vetch. The mixture of clumpers, runners, and mat-formers seems to be working well as a ground cover strategy, and is adapting to the loss of a few species that have yet to come into their own (Waldsteinia fargarioides) or may die out completely (Rubus ‘Betty Ashburner’). Chives dominate this experimental polyculture surrounding a Josta Berry tree. Note the permanent tag in the foreground. A QR code in the bottom right allows student, faculty, and visitors to easily collect data or just to learn more about the polyculture using a custom smartphone app developed at Wellesley. The app will be available on i-tunes later this summer. While we observed significant signs of herbivory among woody species planted with less dense polycultures, specimens surrounded by tall, aromatic herbs appeared to have much less damage. We are inclined to surmise (or hope) that these herbs are protecting/hiding these woodies from herbivory and that these woodies will emerge from the herbaceous understory stronger and better able to respond to future browsing. Performance of Implementation Strategies Overall, the 2011 plantings seem to be thriving and we are pleased with the performance of the various implementation strategies being trialed on-site. Of course, we’ve also had to adapt our thinking/management in some areas. Below are some observations we’ve made about specific strategies and techniques. Weed Suppression: We have reconfirmed our belief that for weed suppression, it is optimal to sheet mulch in the spring or early summer, not the fall. Deep wood chip mulch can suppress weeds for one growing season perhaps, but not for much longer, especially given crown vetch and woody vines like Virginia creeper and bittersweet. In one area slated to have an especially intricate, diverse herb layer, we trialed a combination cardboard and coconut fiber sheet mulch. We have strong evidence that our original sheet mulch strategy for the difficult-to-control crown vetch would have worked well if it had been implemented properly by the contractor. Two shingled layers of cardboard covered in coconut fiber erosion control mat would likely persist for two growing seasons. Because the coconut fiber mat allows the cardboard to dry out, it seems also to allow the cardboard to maintain its integrity long enough to be able to effectively control long-lived herbaceous competitor species. The mat also holds the cardboard down and makes it look pretty decent, actually, while still being able to be mulched over at planting time. Eventually it decays into organic material to feed the soil. Replacing the coconut fiber mat with jute would cost much less, but it is very difficult to find jute that is not treated with kerosene. We found cardboard and deep mulch provided the best weed barrier when applied in the spring, not the fall. Our Nuclei that Merge/Expanding Mulch Donuts strategy would have worked better if we had installed the encircling black plastic mulch kill strips at planting time, much to our chagrin. Having not done this, we had more weed creeping in from the edges of the nuclei that demanded more work from our volunteer crews. Had we laid the plastic donuts before sheet mulching, we would have had a tight perimeter of defense against such creepers in year one and less labor would have been necessary last year, and probably this year as well. With good sheet mulch technique and intensive planting, weed control can take the form of intensive pulses a few times in the growing season. Once ground covers are well established, it will diminish further, though the challenge of finding weeds and eliminating them from a complex polyculture will call forth better pattern recognition and creative removal techniques. We still have much to learn! And that is the point of the garden anyway—to research while we eat our way across the landscape. Plant Densely, Invest in Soil Fertility: In addition to sheet mulching , completely occupying available niches and growing space with desired species, was one of the key implementation strategies deployed at the EETG. We intended that by this time most of the ground cover plants would have filled in the spaces between them for complete ground cover and weed suppression. In the Instant Succession bed we have nearly achieved this goal, with approximately 85% coverage. While we expect the Instant Succession bed will complete that process by midsummer, we have a few problem areas. Budget and plant availability limitations prevented us from planting quite as intensively as we had hoped, leading to more available space for weeds to break through and compete. This has led to the need to weed several beds regularly, but after midsummer, the labor requirement for weeding in most of the area planted in spring 2011 should diminish radically. We’ve also observed that areas without compost additions are not performing as well as those that received compost supplements. Fulfilling a Vision and Promise After only one year, the EETG already feels like the fulfillment of a vision and a promise, but much remains to implement, to learn, and to appreciate. It is the interaction of unique elements that makes the system a whole functioning ecosystem—and we can already see that taking shape at WCBG EETG. We look forward to seeing how the dynamics change as time goes on, and hope we can discover better ways to create functioning polycultures and ecosystems. One Year’s Growth: The most dramatic transformation occurred in the instant succession bed. In just over one calendar year, sheet mulching (pictured in progress at left, 4/2/11) and dense plantings of multi-functional herbaceous plants like chives (in flower at right 5/30/12), yarrow, Astragalus, and Coreopsis transformed this old field into a diverse, food producing garden. Dave Jacke, Dynamics Ecological Design, has been a student of ecology and design since the 1970s, and has run his own ecological design firm since 1984. He holds a B.A. in Environmental Studies from Simon’s Rock College and a M.A. in Landscape Design from the Conway School of Landscape Design. He is the author of the two-volume book, Edible Forest Gardens, the definitive reference text in this new area of horticulture. Keith Zaltzberg, Regenerative Design Group, is an ecological designer who draws on his experiences as an instructor and organic farmer to create beautiful, vital and productive landscapes. Keith holds a B.S. in Environmental Design from the Department of Landscape Architecture and Regional Planning at the University of Massachusetts – Amherst. Like this post? Please share it. Use the icons below to share this post using your favorite social media site.
Bruce Rossmeyer, Daytona Harley dealer, killed in wreck Friday Jul 31, 2009 at 1:18 AM Daytona Beach News-Journal DAYTONA BEACH -- Bruce Rossmeyer, one of the nation's largest Harley-Davidson dealers and a supporter of charitable causes that helped thousands of children, was killed Thursday in a motorcycle crash in Wyoming as he made his way to the Sturgis, S.D., motorcycle rally Rossmeyer, 66, was traveling in the western part of the state in Sweetwater County on Highway 28 about 11 a.m. with five other motorcyclists when they came up to a pickup pulling a camp trailer and tried to pass, according to the Wyoming Highway Patrol. "The pickup slowed and activated his left signal," Lt. Shawn Dickerson said. "Four of the motorcycles passed to the left .¤.¤. When Mr. Rossmeyer attempted to pass, the truck made its left turn and he hit the driver's side door. The sixth motorcycle swerved to the right and avoided collision." Rossmeyer, who was not wearing a helmet, was ejected from his bike and came to rest under the camp trailer, Dickerson said. He was declared dead at the scene. Dickerson described the road as "straight, dry and flat." He said the "extremely rural road" is an option to Sturgis, but not the primary way to travel there. "We do see an influx of motorcycle traffic this time of year," he said. "But we're still eight hours away." Rossmeyer had attended a Harley dealers meeting in Denver and was headed for Thermopolis, Wyo., where he planned to meet a group of custom bike builders called the Hamsters, Grady Pfeiffer, a friend of Rossmeyer's and spokesman for the Hamsters told the Rapid City (S.D.) Journal. From there they were planning to ride to Sturgis. Rossmeyer's wife, Sandy, and two of their children were waiting for him in Sturgis, Pfeiffer said Thursday night. In Ormond Beach, a woman at the front desk of the Harley dealership at Destination Daytona said, "The family isn't ready to make a statement. The media will be notified when they are." Tim Curtis, owner of Houligan's Irish Sports Pub in Ormond Beach, grew up with Bruce and Sandra Rossmeyer's five children - Mandy, Wendy, Randy, Will and Shelly - and said his thoughts and prayers are with the family. "He's a risk-taker, a pioneer and a legend," Curtis said. "But he's the biggest legend to his family. They meant the world to him." Those who only know Rossmeyer from his billboards as they cruise down the highway miss the heart of the man, Curtis said. "I grew up with his kids, and see the family side," he said. "I don't think most people really saw the giving side of him." Rossmeyer's heart for children was a big part of his life, local officials say, whether it was contributing and helping to found Camp Boggy Creek for children with life-threatening illnesses or helping the Boys & Girls Clubs, including the Rossmeyer Family Holly Hill club, named in his honor. "He was a champion for kids here," said Joe Sullivan, chief professional officer for the Boys & Girls Club of Volusia and Flagler Counties. "He overcame some challenges and got in trouble as a young man and said the kids in the club remind him a lot of him." He continued serving on the board of Camp Boggy Creek, southwest of DeLand, and was excited, officials say, at the June meeting describing the plans for the 15th annual Daytona Harley-Davidson Ride for Children in October. "We are just heartsick. This is just horrible," said Sarah Gurtis, spokeswoman for Boggy Creek. "All you had to do was see him around the campers and you knew there was no false smoke. His heart was so focused on those kids." In a 2006 interview with The Daytona Beach News-Journal, Rossmeyer said, "When you go over there and see the results of those kids who are having such a good time, it just gets into your heart." NASCAR driver Kyle Petty formed his own camp for children modeled after Camp Boggy Creek after the death of his son. Rossmeyer helped him to form Victory Junction Gang Camp in North Carolina after years of taking part in the local ride for children. Rossmeyer continued every year to hold similar fundraising rides for Victory Junction and other charities. Born in New Jersey in May 1943, Rossmeyer was a long-time resident of Ormond Beach. He and his wife also lived in Fort Lauderdale. One of the largest Harley-Davidson dealers in the nation, Rossmeyer also co-owned three automobile dealerships. He opened his first motorcycle business, a Harley-Davidson dealership on Beach Street in Daytona Beach, in January 1994. In the next 15 years, he became one of the nation's largest Harley dealers, with 13 dealerships in Florida, Colorado, Massachusetts, Mississippi and Tennessee. He opened the 109,000-square-foot Destination Daytona in October 2005. In 2007, the company employed about 500, including 125 in Ormond Beach, Daytona Beach and New Smyrna Beach. Daytona Beach Mayor Glenn Ritchey said the news "is a terrible tragedy for our area. In addition to being a prominent businessman, Bruce Rossmeyer was involved in many charitable activities for the community. He'll be greatly missed. My heart goes out to his family." Kevin Kilian, senior vice president of The Chamber, Daytona Beach/Halifax Area, who worked with Rossmeyer on Bike Week events, was also was saddened by the news. "Obviously, Bruce Rossmeyer was a big part of the business community and certainly the motorcycle community," he said. "The argument could be made that his presence downtown built Bike Week into the event it is today. And his extension of that event to the Ormond Beach area was a major boost." George Mirabal, executive vice president of The Chamber, worked with Rossmeyer for several years in conjunction with Bike Week and other community events. "Everybody's first reaction is just shock," he said. "Bruce really has been a leader in the community. And I was around when he shaped Bike Week on Beach Street. Everything had been on Main Street till then. And then he reshaped it and spread it to U.S. 1 and to Ormond Beach, to everyone's benefit." His influence also spread to Orlando, where he was a regular courtside at Magic games. "Bruce Rossmeyer was a great fan, friend and sponsor of the Orlando Magic for the majority of our history," chief operating officer Alex Martins said. "Our entire Magic family is shocked and terribly saddened. Our thoughts are with Bruce and his family. We will miss one of our greatest fans." Thursday was the beginning of the 69th Sturgis Motorcycle Rally, which runs through Aug. 9, said Lonnie Isam, owner of Competition Distribution, who deals in vintage Harley-Davidsons and builds 1913 replicas. Isam's business is at the heart of the event activity. "I can see his booth from here," said Isam, who often raced motorcycles in Daytona Beach. "The event is so large. There will be a half-million people here and I am sure a lot of people will stop by his booth. The word will spread and everybody will be sad." Never miss a story Choose the plan that's right for you. Digital access or digital and print delivery. Stay Connected Original content available for non-commercial use under a Creative Commons license, except where noted. The Florida Times-Union ~ 1 Riverside Ave., Jacksonville, FL 32202 ~ Privacy Policy ~ Terms Of Service
--- abstract: 'For a sample of 9 well-studied giant ellipticals we compare the projected radial distribution of their red and blue globular cluster (GC) subpopulations with their host galaxy stellar and X-ray surface brightness profiles. We support previous findings that the surface density distribution of [red]{} (metal-rich) GCs follows that of the host galaxy starlight. We find good agreement between the outer slope of the [blue]{} GC surface density and that of the galaxy X-ray emission. This coincidence of projected radial profiles is likely due to the fact that both blue GCs and X-ray emitting hot gas share the same gravitational potential in equilibrium. When deprojected the X-ray emitting hot gas has a radial density dependence that is the square root of that for the GC density. We further show that the energy per unit mass for blue GCs is roughly half that of the hot gas.' author: - \| Duncan A. Forbes$^{1}$[^1], Trevor Ponman$^{2}$ and Ewan O’Sullivan$^{2,3}$,\ $^{1}$Centre for Astrophysics & Supercomputing, Swinburne University, Hawthorn VIC 3122, Australia\ $^{2}$School of Physics and Astronomy, University of Birmingham, Edgbaston, Birmingham B15 2TT\ $^{3}$Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138, USA title: ' The Baryonic Halos of Elliptical Galaxies: Radial Distribution of Globular Clusters and Diffuse Hot Gas' --- \[firstpage\] globular clusters: general – galaxies: star clusters – galaxies: individual – galaxies: formation Introduction ============ The globular cluster (GC) systems of most, well-studied large galaxies reveal evidence for two subpopulations in colour (and by proxy in metallicity). Soon after the discovery of two subpopulations, it was shown that they have different spatial distributions with the [red]{} (metal-rich) subpopulation being more centrally concentrated than the more extended [blue]{} (metal-poor) one (see Brodie & Strader 2006 and references therein). Furthermore, the mean colours of both subpopulations correlate with the mass of the host galaxy, although the relation for the blue GCs is shallower than that for the red ones (Forbes et al. 1997; Larsen et al. 2001; Peng et al. 2006). The [red]{} GCs are known to share a similar 1D radial, and 2D spatial, distribution with that of the galaxy starlight in elliptical galaxies (Lee et al. 1998; Forbes et al. 2004; Dirsch et al. 2005; Lee et al. 2008; Bassino et al. 2008; Faifer et al. 2011; Strader et al. 2011). They also show similar kinematics (Norris et al. 2006, 2008; Lee et al. 2008; Pota et al. 2012) and stellar populations (Forbes & Forte 2001; Norris et al. 2006; Spitler 2010; Forbes et al. 2011) in many cases (although some exceptions do exist, e.g. Foster et al. 2011). This suggests that the red metal-rich GCs share a common formation history with the stellar component of an elliptical galaxy. The [blue]{} GCs have been associated with elliptical galaxy halos in the literature but the evidence for this is usually more indirect. Their radial surface density profiles are flatter than those of the starlight and they generally extend beyond the radius that can be accurately measured for the starlight. Forte et al. (2007, 2011) have suggested that the ‘halo’ component of elliptical galaxy starlight is associated with the blue GC subpopulation. The halos of large elliptical galaxies also contain diffuse X-ray emitting hot gas. This gas is generally thought to be in hydrostatic equilibrium, although the inner regions may experience strong cooling via bremsstrahlung and line emission, and heating from AGN (e.g. O’Sullivan et al. 2003). In a cosmological context, rare over-dense fluctuations in the early Universe collapse first. Thus the old stellar populations in a galaxy (e.g. the halo field stars and blue metal-poor GCs) are expected to share the same spatial distribution (Moore et al. 2006) and have the same origin (Boley et al. 2009). Recent hydro-dynamical simulations have found similar power-law slopes for the [stellar]{} halos of Milky Way like disk galaxies (e.g –2.6 to –3.4; Font et al. 2011) but lack the resolution to simulate GCs directly and have not yet produced realistic X-ray surface brightness profiles. In the Milky Way, both the halo field stars and the metal-poor GCs do share the same 3D spatial distribution which has a radial power-law slope of $\sim$ –3.5 (Helmi 2008). Furthermore, it is now recognised that a significant fraction of the halo field stars come from disrupted GCs (Forbes & Bridges 2010; Martell & Grebel 2010). As both the blue GCs and the diffuse hot gas occupy the same halo gravitational potential they may reveal the same radial distribution. Based on blue GC counts from a wide-field imaging study of Dirsch et al. (2003) and the X-ray emission detected by the ROSAT satellite, Forte et al. (2005) reported a good coincidence between the projected surface density of blue GCs and the X-ray surface brightness profile out to $\sim$110 kpc for the central dominant galaxy in the Fornax cluster NGC 1399. As far as we are aware this is only case in the literature of a direct comparison between the spatial distribution of blue GCs and X-ray emission. It is therefore important to understand whether NGC 1399 is a special case or whether such similarities in the projected spatial distributions are common. A hint that the latter is true comes from the work of McLaughlin (1999) who pointed out the similarity in the [total]{} GC system surface density profile with the combined stellar and hot gas radial profiles for M87, NGC 1399 and NGC 4472. In the halo of a galaxy, these profiles are dominated by the blue GCs and hot gas respectively. Lee et al. (2010) studied the large-scale distribution of GC candidates through out the Virgo cluster using Sloan Digital Sky Survey data. They concluded that this distribution was qualitatively similar to that of the large-scale X-ray emission; with the blue GCs more closely resembling the X-ray emission than the red ones. Finally, we note that the global X-ray emission from giant elliptical galaxies correlates better with the velocity dispersion of the blue rather than the red GC subpopulation (Lee et al. 2008; Pota et al. 2012). In this paper, we have collected data from the literature for a small sample of giant elliptical galaxies that have diffuse hot gas halos and radially extended GC systems that can be clearly separated into blue and red subpopulations. We explore the radial distributions of these baryonic halo tracers and briefly discuss their interpretation. Elliptical Galaxy Sample ======================== Our sample consists of two central cluster galaxies (M87 and NGC 1399), six giant ellipticals in groups or clusters and one isolated field galaxy as listed in Table 1. Most are the central brightest galaxies in their host group/cluster (i.e. BGG/BCG). Table 1 includes the type of galaxy, its environment, hot gas temperature, distance, K-band luminosity, stellar velocity dispersion, physical scale of 1 arcmin and the source of the galaxy surface brightness profile. Apart from the field galaxy NGC 720, all are massive galaxies with M$_K$ $\sim$ –25 (M$_V$ $\sim$ –22) that dominate their group or subgroup within a cluster, i.e. lie at the centre of their local potential well and X-ray emission. In the case of the cD galaxy M87, it lies at the centre of Virgo cluster potential well whereas NGC 4472 is the brightest galaxy in the Virgo cluster dominating its own subgroup. NGC 1407 is the brightest galaxy in the massive Eridanus group (Romanowsky et al. 2009). NGC 4365 lies in the W$'$ cloud, a group lying some 5 Mpc behind the Virgo cluster. NGC 4636 lies in an X-ray distinct subgroup to the South of the main Virgo cluster. NGC 4649 is a giant Virgo elliptical galaxy. NGC 5846 is the brightest galaxy in the NGC 5846 group. Our sample of elliptical galaxies was selected, from the literature, to have extended radial profiles for both GCs and diffuse X-ray emission. In particular, the blue GC density profile was required to extend to at least 8 arcmin (about 45 kpc at the typical distance of our sample). Further details of the selection process and literature data are discussed below. ---------- ------ -------- ------- ------- -------- ----------------- --------- ------------ Galaxy Type Envir. T$_X$ Dist. M$_K$ $\sigma_{\ast}$ kpc/$'$ SB profile (keV) (Mpc) (mag) (km/s) M87 cD Virgo 2.50 16.7 –25.29 334 4.9 (1) NGC 720 gE Field 0.57 24.0 –24.63 241 7.0 (2) NGC 1399 BCG Fornax 1.13 19.0 –25.06 346 5.5 (3) NGC 1407 BGG Group 0.87 23.8 –25.15 271 6.9 (4) NGC 4365 BGG Group 0.64 21.4 –25.00 256 6.2 (5) NGC 4472 BCG Virgo 0.97 16.1 –25.61 294 4.7 (6) NGC 4636 BGG Group 0.69 15.9 –24.57 203 4.6 (6) NGC 4649 gE Virgo 0.80 16.5 –25.34 335 4.8 (7) NGC 5846 BGG Group 0.71 26.7 –25.18 239 7.8 (8) ---------- ------ -------- ------- ------- -------- ----------------- --------- ------------ ---------- --------- --------- ---------------- ---------------- ---------- Galaxy Density Filters $\sigma_{BGC}$ $\sigma_{RGC}$ N$_{GC}$ (km/s) (km/s) M87 (1) gri 414 380 13000 NGC 720 (2) gi – – 660 NGC 1399 (3) CR 337 277 5410 NGC 1407 (4) gri 239 212 2640 NGC 4365 (5) gri 238 261 2500 NGC 4472 (6) BVR 337 257 6300 NGC 4636 (7) CR 236 194 3000 NGC 4649 (8) CT$_1$ 197 218 5100 NGC 5846 (9) gri 264 206 2200 ---------- --------- --------- ---------------- ---------------- ---------- X-ray Surface Brightness Profiles ================================= The X-ray emission of giant elliptical galaxies is dominated by diffuse hot gas and their surface brightness profiles tend to range from core-like to power-law in their inner regions, with an outer power-law slope. Such profiles are usually quantified by a so-called beta model, i.e.\ $S(r) = S_0[1 + (r/r_c)^2]^{-3\beta_{X} + 0.5}$ (1)\ Here we take the beta model fit parameters (i.e. the core radius r$_c$ and the $\beta_X$ value) from the X-ray surface brightness profiles in the literature. Although the Chandra satellite has superior resolution and XMM-Newton has better sensitivity, the ROSAT satellite is generally preferred for its extended radial coverage when studying the outer halos of giant elliptical galaxies. For the two central cluster galaxies (M87 and NGC 1399) in our sample we use beta model fits to the ROSAT X-ray surface brightness profiles. These fits extend to over 100 arcmin for M87 (Bohringer et al. 1994) and to 40 arcmin for NGC 1399 (Jones et al. 1997). For NGC 5846 a deep (120 ksec) Chandra image is available from Machacek et al. (2011). For the other giant ellipticals, X-ray profiles come from ROSAT data in the large sample study of O’Sullivan, Ponman & Collins (2003). A detailed description of the data reduction and analysis can be found in O’Sullivan et al. Briefly, periods of high background (deviating by $>$2$\sigma$ from the mean event rate) were excluded from each dataset, point sources of $>$4.5$\sigma$ significance were excluded (excepting those within the D$_{25}$ radius of the target galaxy), and a background model determined based on a large-radius annulus. A 0.5-2 keV image was extracted and corrected for vignetting, and a flat background level was determined and subtracted from the image. A standard beta model was fit to the data, after convolution with the point spread function appropriate for the mean photon energy of the source. All the sample galaxies, including M87 and NGC 1399, are highly X-ray luminous and gas-rich. We therefore expect individual X-ray binaries to have little, or no impact, on the surface brightness fits. In a Chandra X-ray study that included our galaxies, Diehl & Statler (2007) estimated an average unresolved fraction of $<8\%$. A small number of bright point sources are visible in the O’Sullivan et al. data, and they are excluded from the fit. The remaining unresolved sources could potentially affect the fit in the galaxy core, but we are primarily interested in the outer parts of each galaxy, where GCs can be reliably detected. Here, the density of X-ray binaries will be low, and therefore very unlikely to have any significant influence on the surface brightness modelling. We also note that when X-ray binaries are located in GCs they are typically found in red rather than blue GCs (Paolillo et al. 2011). We exclude all galaxies that have X-ray profiles classified as ‘uncertain’ (e.g. NGC 4552) or noted to have strong AGN activity (e.g. NGC 5128) by O’Sullivan et al. (2003). Globular Cluster Surface Densities ================================== The GC data used here come from a variety sources in the literature. The original imaging data should be multi-filter (to clearly distinguish the blue and red subpopulations) with a wide field-of-view (to cover a large radial range). The first criterion of using more than one filter is met by most GC studies of giant ellipticals. Thus with sufficient numbers of GCs the system can be separated into blue and red subpopulations based on a simple colour division. Here we adopt the blue/red definitions from the original literature studies. For the second criterion, our sample is restricted to those galaxies which have GC system surface density profiles out to at least 8 arcmin (about 45 kpc for our sample). The minimum radial extent is for NGC 4649 which reaches to 8.75 arcmin using data from Lee et al. (2008). The typical effective radius of the galaxy starlight for our sample is 5–10 kpc; thus the GC data typically probe to several effective radii in terms of the host galaxy starlight. Requiring large radial coverage of nearby galaxies effectively restricts studies to those that use a ground-based telescope. Our final sample of giant elliptical galaxies is summarised in Table 1. All GC profiles have been corrected for background contamination in the original work. However, the level of the background contamination and the ability to subtract it accurately vary for each dataset. This uncertainty is generally not captured in the (Poisson) error bars quoted in the literature. Although good seeing conditions help for GC studies, the introduction of a third filter can significantly decrease background levels as GC candidates can be selected in colour-colour space. For example, Romanowsky et al. (2009) found a contamination rate of $\sim$5% in follow-up spectroscopy of GCs in NGC 1407 selected from three filters. In Table 2, along with the source of the GC surface density data, we list whether it comes from 2 or 3 filter imaging. Thus the best quality GC data are available for M87, NGC 1407, NGC 4365, NGC 4472 and NGC 5846. The total number of objects in the GC system, from the literature, is also included. Traditionally, GC surface density profiles have been fit by a simple power-law. However, this approach often fits the central regions in which the density flattens off, perhaps due to destruction effects (Miocchi et al. 2006) and hence tends to underestimate the outer slope. A better approach, which is becoming more common (e.g. Strader et al. 2011; Blom, Spitler & Forbes 2012) is to fit Sersic (1968) profiles to the GC density data as has been done for galaxy surface brightness profiles for a number of years. Here we have decided to fit the GC surface density data with the same beta profile form as used in fits to the X-ray surface brightness data in order to facilitate a direct comparison. Such beta profiles, like Sersic ones, fit an inner core region and the changing slope of the profile. Results ======= M87 --- In Figure 1 we show a comparison between the GC system surface density and the X-ray emission as quantified by a beta model (Eq. 1) for the central galaxy in the Virgo cluster M87. Although not optically the brightest in the cluster, it lies at the centre of the Virgo cluster X-ray emission. In this figure, and subsequent ones, the X-ray profile has been normalised to a value of 1 at 10 arcmin radius and the GCs have been arbitrarily normalised in the vertical axis. For the [blue]{} GCs we show the individual data points and a beta model fit. We also show the X-ray beta model fit and a $\pm$5% variation (a typical value for well-constrained X-ray profiles) on the $\beta_X$ slope. The blue GCs and X-ray beta model for M87 reveal a similar slope from a few arcminutes to 30 arcminutes. Only in the inner regions, in which the X-ray emission may be affected by thermal heating asociated with the AGN/jet, does the coincidence begin to break down. We note that Lee et al. (2010) measured a power-law slope of –1.49 $\pm$ 0.09 for the blue GCs within 40 arcmin, and that this compares well with our data which have a power-law slope of –1.54 $\pm$ 0.04. We also show the similarity between the [red]{} GC surface density profile and that of the galaxy starlight (from Kormendy et al. 2009). Such a connection between the red GC subpopulation and the starlight of the galaxy has been observed in many galaxies as noted in the Introduction (see Brodie & Strader 2006 for an overview). NGC 1399 -------- In Figure 2 we show the GC, X-ray and stellar profiles for the central galaxy of the Fornax cluster NGC 1399. Forte et al. (2005) highlighted the similar slopes, between 1 and 20 arcmin, of the blue GC data of Dirsch et al. (2003) and the X-ray surface brightness profile of Jones et al. (1997). Here we use the same X-ray data (rather than the more recent Chandra data of Scharf et al. (2005) which only extend to less than 2 arcmin) but show the more recent and more radially extended GC data of Bassino et al. (2006). The figure supports the claim of Forte et al. but also shows that the agreement in profile slopes begins to break down for radii beyond 20 arcmin. We note that the outer region GC data are highly sensitive to contributions from other Fornax cluster galaxies (e.g. NGC 1404; Bekki et al. 2003, Schuberth et al. 2011). We also show the red GCs compared to the stellar surface brightness profile from Forte et al. (2005), again with an arbitrary normalisation. Similar to the situation in M87, the red GCs and the starlight show consistent profile slopes. NGC 5846 -------- In Figure 3 we show the GC, X-ray and stellar profiles for the central group galaxy NGC 5846. The X-ray beta model fit, to the deep (120 ksec) Chandra X-ray surface brightness profile, is from Machacek et al. (2011). They note that the galaxy shows signs of central AGN activity (e.g. X-ray cavities) and non-hydrostatic gas motions, yet the profile is fairly well represented by a single beta model to 12 arcmin. As for M87 and NGC 1399, the red GCs are well matched to the starlight profile, while the blue GCs are consistent with the X-ray profile over most radii (the innermost regions may be affected by GC destruction processes; Miocchi et al. 2006). The O’Sullivan et al. sample ---------------------------- In Figures 4 and 5 we show galaxies from the giant elliptical galaxy sample of O’Sullivan et al. (2003) for which we were able to find GC surface density data that extended to at least 8 arcmin (i.e. well beyond any GC core region). The figures show the [blue]{} GC surface density data from the literature, beta model fits to those data, and beta model fits (and their uncertainty) to the ROSAT X-ray surface brightness profiles as determined by O’Sullivan. For most galaxies the surface density of blue GCs in the outer regions is well-matched to the X-ray profile. The main exception is NGC 4365 which reveals a GC profile that is significantly flatter than the X-ray one. This galaxy is currently undergoing an interaction (Mihos et al. 2012) and it is possible that the accreted galaxy has contributed extra GCs to the outer regions ($>$ 10 arcmin) of NGC 4365. All of the GC systems in Figures 4 and 5 reveal a flattening (i.e. towards a constant density) at small radii. This has been observed in many GC systems (Forbes et al. 1996) and may be due to GC destruction processes, such as bulge shocking (Miocchi et al. 2006). Galaxy X-ray $\beta_X$ $\beta_{BGC}$ $\beta_{RGC}$ ---------- ------- --------------------------- ----------------- ----------------- M87 (1) 0.47 0.43 $\pm$ 0.13 0.49 $\pm$ 0.01 NGC 720 (2) 0.483 $\pm$ 0.01 0.60 $\pm$ 0.09 0.72 $\pm$ 0.12 NGC 1399 (3) 0.35 0.42 $\pm$ 0.05 0.51 $\pm$ 0.02 NGC 1407 (2) 0.56$^{+0.02}_{-0.01}$ 0.58 $\pm$ 0.17 0.86 $\pm$ 0.04 NGC 4365 (2) 0.60$^{+0.04}_{-0.03}$ 0.46 $\pm$ 0.12 0.61 $\pm$ 0.03 NGC 4472 (2) 0.597$^{+0.009}_{-0.008}$ 0.67 $\pm$ 0.22 0.52 $\pm$ 0.02 NGC 4636 (2) 0.535$^{+0.007}_{-0.006}$ 0.69 $\pm$ 0.09 0.53 $\pm$ 0.02 NGC 4649 (2) 0.567$\pm{0.08}$ 0.55 $\pm$ 0.09 0.63 $\pm$ 0.11 NGC 5846 (4) 0.45 0.51 $\pm$ 0.10 0.54 $\pm$ 0.09 Mean – 0.51 $\pm$ 0.03 0.54 $\pm$ 0.03 0.60 $\pm$ 0.04 As mentioned earlier, we have fit the blue GC surface density data with a beta model (Eq. 1). For NGC 4636 we were unable to obtain stable fits to the error-weighted data and so we chose to fit with equal weighting. The GC data for NGC 4636 show an increased density at large radii. This is likely an indication of the uncertainty in the background subtraction. If we fit only the blue GC data interior to 12.5 arcmin we derive the same beta slope within the errors quoted in Table 3. For NGC 4649 the limited radial extent did not allow for a beta model fit for the blue GCs. In this case we fit a simple power-law fit to the data beyond 4 arcmin which gives an equivalent beta slope of 0.55 $\pm$ 0.09 and is quoted in Table 3. The results of our beta model fitting to the blue GC density profiles are given in Table 3, along with the $\beta_X$ values from the X-ray surface brightness fits from the literature. Table 3 also gives mean values and the error on the mean. The X-ray and blue GC beta slopes are consistent within the errors, while the red GCs have higher beta values than the X-ray profiles at the $\sim$2$\sigma$ level. Figures 4 and 5 also show the [red]{} GC data with the galaxy surface brightness profile from the literature. The galaxy profiles are from Goudfrooij et al. (1994) for NGC 720; Spitler et al. (2012) for NGC 1407; Blom, Spitler & Forbes (2012) for NGC 4365; Caon et al. (1994) for NGC 4472 and NGC 4636 and MacDonald et al. (2011) for NGC 4649. Although the galaxy starlight does not extend as far as the GC data (particularly for NGC 720), the GCs and the starlight show similar slopes in their outer regions. Given that the blue and red GCs occupy the same gravitational potential but have different density profiles, the Jeans equation suggests that they also have different orbital anisotropy properties. Summary ------- We support previous findings that the [red]{} GC density profiles generally follow the starlight in elliptical galaxies. Most elliptical galaxies in the sample show good coincidence between the outer slope of the [blue]{} GC profile and the X-ray surface brightness. We note that the measured GC slopes are dependent on the level of background contamination and hence the overall quality of the data which is not captured by the purely Poisson errors given in the literature. The average slopes of the blue GCs and X-ray emission are consistent within the errors, although our sample is small. Discussion ========== In the previous section we showed that the outer slope of the X-ray emission (with a mean slope of $\beta_X$ = 0.51 $\pm$ 0.03) was in good agreement, in most cases, with the blue GCs surface density slope (mean $\beta_{BGC}$ = 0.54 $\pm$ 0.03). Could this similarity between the projected blue GC and X-ray profiles indicate a direct physical connection between the metal-poor GC system and the diffuse hot gas in an elliptical galaxy halo? One possibility is that GCs have formed within hot gas that permeates the halos of giant ellipticals. For example, in the model of Fall & Rees (1985) the hot gas acts to compress colder gas clouds. For metal-poor gas this gives rise to a characteristic mass of $\sim$10$^6$ M${_\odot}$ which is typical of GCs. However a problem with this scenario is that metal-poor GCs also form in dwarf galaxies which lack hot gas halos. More probably, the coincidence in profile shape between blue GCs and X-ray emission from hot gas reflects the fact that for our giant elliptical galaxy sample both halo tracers are in equilibrium within the potential well centred on the host galaxy. The observed correlations of hot gas X-ray emission and the blue GC velocity dispersion (Lee et al. 2008; Pota et al. 2012) further supports this interpretation. If this is the case, then the similar outer slopes seen for the blue GCs and the X-ray emission has an interesting implication for the relative density profiles of the two tracers and their specific energies. The X-ray emissivity, which projects to give surface brightness, is proportional to the square of the hot gas density, whereas the projected GC surface density scales linearly with the GC density. So similar outer slopes in projection imply that the hot gas density scales with the GC density to the power of 0.5. In other words, the GCs have a steeper 3D radial density distribution than the hot gas. The radial distribution of a tracer in equilibrium within a gravitational potential well is related to its specific energy, and hence the relative slopes of the gas and GC profiles will depend on the ratios of their specific energies, traditionally denoted $\beta_{spec}$ in the cluster literature. In our case:\ $\beta_{spec} = 0.5(3\sigma_{BGC}^2) ~/~ (3kT_X/2m)$, (2)\ where $\sigma_{BGC}$ is the blue GC velocity dispersion, $T_X$ is the hot gas temperature, $k$ is the Boltzman constant and $m$ is the mean particle mass of the hot gas. Using $m =0.6$ amu, this reduces to:\ $\beta_{spec} =(\sigma_{BGC} ~/~ 1000\,{\rm km~s^{-1}})^2 ~(6.22\,{\rm keV}/T_X)$. (3)\ Taking X-ray temperatures (T$_X$) from Table 1 and blue velocity dispersions ($\sigma_{BGC}$) from Table 2, the resulting $\beta_{spec}$ values have a mean of 0.52 for our sample. In other words, the blue GCs have about half the specific energy of the hot gas. Assuming that the GCs are virialised and follow the Jeans equation, and the hot gas is in hydrostatic equilibrium, the value of $\beta_{spec}$ is related to the gradients in the density and temperature/velocity dispersion of the two tracers by equation 35 from Bahcall & Lubin (1994). Although kinematic studies of GCs are limited, to first order blue GCs reveal flat velocity dispersion profiles (e.g. Lee et al. 2008; Pota et al. 2012). The orbital anisotropy for blue GCs is not well determined but orbits appear to be close to isotropic on average. Similarly, X-ray temperature profiles, beyond the very inner regions, are close to flat on average (O’Sullivan et al. 2003). For the case of isotropic GC orbits with flat velocity dispersion gradient and isothermal gas, the equation simplifies such that:\ $\beta_{spec} = \frac{d ln \rho_{gas} ~/~ d ln r}{d ln \rho_{BGC} ~/~ d ln r }$ (4)\ where $\rho_{gas}$ and $\rho_{BGC}$ are the density of hot gas and blue GCs respectively. Hence, since we find $\beta_{spec}$ $\sim$ 0.5, it follows that we would expect the logarithmic slope of the gas density to be one half of that of the blue GCs, and hence the X-ray emissivity (scaling as density squared) would indeed have the same slope as the density of blue GCs. For a beta model (Eq. 1) the logarithmic slope at large radii is given by $-6 \beta + 1$. Given the mean beta value for the blue GCs of $\beta_{BGC} = 0.54$ this corresponds to a projected outer slope of -2.24. If the GCs have spherical symmetry then the [deprojected]{} 3D slope for the blue GCs will be -3.24 (in comparison the surface density of blue GCs in the Milky Way has a 3D slope of –3.5; Helmi 2008). In comparison, the projected X-ray emissivity (with mean $\beta_X$=0.51 from Table 3) has a slope of -2.06, and hence a 3D slope of -3.06, so that the average 3D gas density slope is -1.53, roughly one half that of the blue GCs. This result is reminiscent of that found by Osmond & Ponman (2004) for galaxy groups. They derived the specific energy of the galaxies and compared it to that for the hot gas in galaxy groups. The groups had a mean $\beta_{spec}$ = 0.75 indicating that the galaxies had a lower specific energy than the hot gas within the group. (We note that galaxy clusters have $\beta_{spec}$ $\sim$ 1.) Here, we find that the blue GCs have a specific energy ($\beta_{spec} \sim 0.5$) lower than that of galaxies in groups and much lower than the expected value for the group potential. Thus whatever process gives rise to blue GCs in the halos of giant elliptical galaxies must deposit them with a relatively low specific energy. If blue GCs have been accreted relatively recently then the likely source would be more massive galaxies which, unlike dwarfs, are able to lose specific energy on a Gyr timescale through dynamical friction. However, perhaps more likely is the accretion and disruption of dwarf galaxies at early times when the group/cluster was less massive than today. Summary and Conclusions ======================= For our sample of 9 giant ellipticals we have shown that the 1D radial surface density of [red]{} GCs, beyond the inner regions, is well matched to the stellar surface brightness profile. Thus, combining with literature studies, [red]{} GCs have the following properties:\ $\bullet$ similar 1D radial distribution to the host galaxy stars\ $\bullet$ similar 2D spatial distribution to the host galaxy stars\ $\bullet$ similar stellar populations to the host galaxy stars\ $\bullet$ correlate with galaxy stellar mass and stellar velocity dispersion\ The [blue]{} GCs in the Milky Way share many properties with the stellar halo. For elliptical galaxies the connection between the [blue]{} GCs and the hot gas halo was based on the similarity in 1D radial profiles for one galaxy, NGC 1399 (Forte et al. 2005). Here we have revisited NGC 1399 and included an additional 8 giant ellipticals, finding that in most cases there is a good coincidence between the outer slopes of the [blue]{} GC surface density and the X-ray surface brightness. Thus we provide evidence for a connection between [blue]{} GCs and the halos of elliptical galaxies that until now was largely conjecture. This finding means we can use [blue]{} GCs as a halo tracer for lower luminosity ellipticals for which the X-ray emission is undetected. As the X-ray emission scales with gas density squared and blue GC surface density scales linearly with GC density, the similarity in [projected]{} outer slopes implies that the 3D density distribution of the hot gas scales with the blue GC density to the power of a half. Consistent with this, we calculate that the specific energy of the blue GCs is about one half that of the hot gas. ![image](m87.eps) ![image](n1399.eps) ![image](n5846.eps) Acknowledgments {#acknowledgments .unnumbered} =============== We would like to thank A. Romanowsky, R. Crain, J. Strader, C. Frenk and G. Poole for useful discussions. Thanks to V. Pota, K. Woodley, K. Rhode, L. Spitler and S. Kartha for supplying globular cluster profile data. 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Analysis of the uncoupling protein-1 (UCP1) gene in obese and lean subjects: identification of four amino acid variants. Uncoupling protein-1 (UCP1) is uniquely expressed in brown adipose tissue (BAT) and of major importance for the tissues thermogenic capacity. This study was undertaken to detect variants in the UCP1 gene by single strand conformational polymorphism (SSCP) analysis and subsequent sequencing, and determine their potential association with obesity. Four variants predicting for amino acid substitutions were detected, of which Arg40Trp (exon 1) and Lys257Arg (exon 5) were rare mutations. In contrast, the allele frequency of a polymorphism in exon 2 predicting for an Ala64Thr substitution was 8.2% in a cohort of 293 obese children and adolescents compared to 4.1% in 134 lean individuals, while the allele frequency of a Met229Leu variant (exon 5) was not markedly different between the obese (10.4%) and lean (12.0%) study groups. Although one of the identified polymorphisms tends to have a higher frequency in obese than in lean subjects, variants of the UCP1 gene do not seem to contribute significantly to the development of early-onset obesity in the German population.
MELBOURNE: Mothers unable to breastfeed their babies are bypassing registered milk banks in Australia and reaching out to strangers on social media for donations of human milk. One such network called ‘Human Milk 4 Human Babies’ connects parents in need of breast milk with those willing to provide it free of charge. Users in Australia have responded to requests for milk donations for babies as young as three weeks. In one case, users also donated to a man with cancer, whose wife appealed for human milk after their doctor recommended it to boost his immune system. Experts, however, warn of the risks involved in sharing milk, which has the potential to be a carrier for bacteria and viruses, including HIV . Director of Mothers’ Milk Bank, Marea Ryan , said peer-to-peer milk-sharing was potentially dangerous, and urged mothers to use screened and registered milk bank services. “The risks are of those viruses passing through to the baby (and) if they haven’t had good hygiene at the point of collecting the milk there’s potential there for bacteria in the milk,” Ryan said.
Q: issue in transfer file to remote machine on executing shell script through php i am executing script file through php as shell_exec(sh script.sh) script.sh is the name of the script file. This script is used to transferring file say 'abc' to remote machine. When I execute script file through terminal as ./script.sh it successfully transfer file to remote machine but when execute same script file through php it could not transfer file to remote.Any suggestions are welcome... A: When you execute it in the shell you are using your user credentials. When running from withih a PHP script script you are using apache user or group credentials. Make sure apache can run your script check here Executing a Bash script from a PHP script
A pediatric critical care perspective on vitamin D. The mechanisms of action of vitamin D are the subject of intense investigation. Evidence now suggests vitamin D affects immune function and cell proliferation, prompting interest in its role in critical illness and cardiac disease. Multiple studies demonstrate strong associations between vitamin D deficiency and severity of illness including need for higher inotrope support, more fluid resuscitation, and longer intensive care unit stay. The pediatric cardiac population may be at even more risk and nearly twice as likely to be deficient compared to the noncardiac population. Low vitamin D levels have been found in postoperative cardiac patients, where investigators speculate cardiopulmonary bypass alters levels directly or indirectly. Patients with congestive heart failure who are deficient also seem to benefit from vitamin D supplementation. This review summarizes recent studies in children that investigate the relation between vitamin D status and clinical outcomes in the critically ill including those with cardiac disease.
INTRODUCTION ============ "Information flow, exchange and storage," arguably the basis for all modern genetics and genomics research, was named one of the five core concepts necessary for biological literacy by the National Science Foundation\'s (NSF) high-profile report, Vision and Change: A Call to Action ([@B1]). Furthermore, this report describes the importance of integrating topics related to information flow in an in-depth way throughout the biology curriculum. The 2012--2013 Advanced Placement Biology Curriculum Framework echoes the NSF in their "Big Idea 3: Living systems store, retrieve, transmit and respond to information essential to life processes" ([www.collegeboard.org](http://www.collegeboard.org)). Indeed, the concept of information being stored in DNA molecules, copied into RNA intermediates, and expressed in proteins that carry out cellular functions, is known as the "central dogma" of molecular biology. Francis Crick first described the central dogma as "the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred from protein to either protein or nucleic acid" ([@B14]). The canonical interpretation of the central dogma is that genetic information (DNA) is used to generate transient messenger molecules (RNA) that are themselves used to direct synthesis of particular protein products and that the proteins are responsible for most cellular functions. In a recent review "revisiting" the central dogma, [@B57] wrote, "The idea of a 'dogma' in science has always struck me as inherently self-contradictory. The scientific method is based upon continual challenges to accepted ideas and the recognition that new information inevitably leads to new conceptual formulations." The discoveries of reverse transcription, catalytically active RNA molecules, and posttranscriptional modification of RNA molecules are examples of a few of the many exceptions to the central dogma. And while the traditional representation of the central dogma ([Figure 1](#F1){ref-type="fig"}) suggests a very simplistic mechanism for information flow, in reality, the processes that direct the synthesis of each macromolecule are numerous and complex. Most postsecondary educators would likely agree that concepts related to the central dogma are crucial to their curricula in courses such as those in introductory biology, cell and molecular biology, genetics, and developmental biology, as well as in many others. As the fields of genomics and bioinformatics continue to be revolutionized by advancing technologies such as whole-genome sequencing ([@B43]; [@B37]), it is critically important that we prepare our biology students to think deeply and carefully about information flow. ![Typical depiction of the central dogma concept.](338fig1){#F1} The molecular basis of inheritance and information exchange, though, is a difficult topic for biology students ([@B51]; [@B62]; [@B2]; [@B34]; [@B66]; [@B35]), and many students have weak mental models of the relationships among genes, alleles, and chromosomes ([@B42]). Almost every biology textbook (both secondary and postsecondary level) describes the work of Austrian monk Gregor Mendel and his famous pea experiments as an introduction to genetics. Almost none of these books, however, makes an explicit connection between the phenotype of the pea (e.g., round versus wrinkled) and the expression of a protein (e.g., a starch branching enzyme; [@B59a]). Many students who struggle with concepts related to gene structure and expression do not appreciate the significance of the central dogma or information flow in the context of gene regulation ([@B27]), which is an essential concept in molecular biology. Much work also demonstrates that high school curricula do not provide adequate scaffolding for students to deeply learn central dogma concepts ([@B34]; [@B58]) For example, [@B34] reported that, of 482 surveyed high school students, none knew that a final product was connected with a gene. Data obtained through the National Center for Education Statistics (<http://nces.ed.gov>) demonstrate that only 21% of tested 12th-grade high school students could correctly answer the multipart question "What is a gene? (genetic instructions), What is it made of? (DNA), What is the major function of a gene? (to code for protein product)." When asked to explain what a "broken gene" is, only 3% correctly described a broken gene in terms of a change in the DNA sequence and/or a change in genetic instructions. This knowledge gap may be due, in part, to the fact that few high school students know what a gene is---a concept that scientists still struggle to define in the midst of our bioinformatics and genomics explosion ([@B52]; [@B53]; [@B55]). In fact, the definition of a gene has changed dramatically since Mendel\'s original conception of a unit of heredity, including the post--Watson and Crick definition of a section of DNA that encodes a protein and a recent computational characterization as a subroutine within the genomic operating system ([@B21]). For experts, this multitude of definitions is not generally problematic, because the context is immediately recognized and applied. However, having multiple definitions that are context dependent may be very confusing to students, particularly considering that most high school and early college students are "dualists" according to Perry\'s stages of intellectual development ([@B54]). In other words, they see things in black and white and have trouble with multiple "right" answers. There are ample data to show that a large percentage of first-year biology students enter with weak or missing mental models about genes and gene expression (e.g., [@B50]; [@B58]; <http://nces.ed.gov>). It is little wonder, then, that learning about the complex molecular processes that maintain genomic integrity, drive gene expression, and control protein synthesis is problematic for students. As [@B31] stated, "Understanding molecular properties and processes has been a challenge, in large part because molecules and their properties are not available to direct perception." This challenge is most likely confounded by the fact that many students entering college are poor problem solvers with underdeveloped formal reasoning skills ([@B22]; [@B32]; [@B65]). Thus, biology instruction must be designed to provide practice with formal reasoning in order to help students develop deep, transferable learning of biological concepts like gene expression. College students, of course, are not blank slates; they bring diverse experiences, background, and prior knowledge into the classroom. Issues can arise, however, when these prior conceptions are incorrect or incomplete; especially when an instructor is not aware of these shortcomings. In Science Teaching Reconsidered: A Handbook, conceptual misunderstandings are described as phenomena that occur when students are not forced to confront the discrepancies between their own preconceived ideas and real-world observations. The failure to critically examine one\'s own mental models leads to weak, faulty models, with little confidence behind them ([@B40]). Conceptual misunderstandings are problematic, because their existence often interferes with learning new concepts ([@B38]), especially if the misconceptions seem rational and useful to the learner at the time ([@B18]). Several decades ago, [@B19] explored what we believe is the first published account of a central dogma misconception held by college biology students: the idea that amino acids are synthesized during the process of genetic translation. This is an important conceptual misunderstanding, as students with this belief develop incorrect ideas about molecular processes associated with protein translation and biomolecule synthesis. Such foundational weakness can be detected in student populations with careful assessment of conceptual understanding. A number of instruments, such as the Genetics Concept Assessment ([@B61]), the Genetics Literacy Assessment ([@B7]), the Biological Concepts Instrument ([@B20]), the Introductory Molecular and Cell Biology Assessment ([@B59]), and the Meiosis Concept Inventory ([@B26]), have been developed in an effort to help postsecondary instructors identify gaps in knowledge about essential biological processes and evaluate learning after instruction. Many of these concept assessment tools include questions that rely on deep conceptual understanding of information flow. While the published inventories cover many topics related to information flow, they are not exhaustive, and our own experiences with first- and second-year biology majors suggested there are some foundational concepts that need further exploration. While carefully designed assessments such as concept inventories help instructors determine understanding of concepts, they may not be as useful for assessing the differences between expert--novice reasoning. Cognitive and developmental psychologists agree that expertise in a discipline involves not only the collection of knowledge but also the ability to organize, adapt, retrieve, and apply knowledge in a dynamic way; such as when experts are presented with a novel research finding in their disciplinary field ([@B41]; [@B5]; [@B10]). The difference between novice and expert reasoning has been explored most fully in physics education research. For example, [@B11] elegantly described several key differences in how novices (physics undergraduate students), midlevel (physics graduate students), and experts (physics faculty) solve physics problems. Experts thought about unifying principles, such as Newton\'s laws, while students focused on superficial aspects of the problem, such as whether a ramp or inclined plane was in use. More recently, the novice--expert continuum was illustrated in a biology context by [@B60]. In this study, biology students and biology faculty were asked to sort a number of biology-based problems printed on cards. Students sorted the cards based on surface features (e.g., what type of organism was used in the problem), while faculty sorted the cards by the underlying biological concept (e.g., evolution). Differences in how experts and novices interpret and use scientific representation has also been investigated by the discipline-based education research (DBER) community. Formulas, structural diagrams, cartoon images, and models are tools created by scientists to explain, demonstrate, or quantify their research. When these representations make their way into high school and college textbooks, slides, and work sheets, experts have little problem interpreting and using these representations. Students, though, often cannot make connections between complex processes and scientific representations and probably do not appreciate their importance or complexity. [@B31], for example, described the importance of representations such as structural diagrams and chemical equations in the daily lives of typical chemists in either an academic laboratory setting or a pharmaceutical laboratory setting. These visual representations for compounds and processes invisible to the human eye were the common language spoken by true academic and professional chemists. Observational studies of paired college chemistry students, on the other hand, demonstrate only limited use of visualization during actual laboratory experimentation ([@B30]), demonstrating that novices and experts use scientific representations differently. In this paper, we focus on the canonical representation of central dogma, and transcription in particular, to gain insight into student conceptions of these processes. We report two novel and interesting misinterpretations of the central dogma that persist among different populations of postsecondary biology students: 1) DNA is transformed into RNA, and 2) the mRNA molecule exists before transcription takes place. We classify these findings as misconceptions, as they can be described as "scientifically inaccurate understanding that students have developed about natural phenomena" ([@B4]). The incorrect ideas we have uncovered would likely interfere with student learning rather than move students toward deeper understanding of information flow. We support our findings through analysis of open-ended responses, student interviews, and results of new conceptual assessments based on research findings. METHODS ======= All student data presented were gathered with institutional review board approval. Students from four 4-yr institutions in the northern United States were recruited for these studies (see [Table 1](#T1){ref-type="table"}): a large private university (institution A: 15,000 undergraduates, 12% minority), two small private universities (institution B: 2000 students, 12% minority; institution C: 2100 total, 14.7% students of color), and a medium-sized public university (institution D: 7100 undergraduates, 12.5% minority). ###### Student populations studied^a^ Data gathered Course Level Institution Number of students ---------------------------------------------------------------------- ---------------------------- ---------------------- -------------------------- -------------------- C-maps: "What is molecular biology?" Molecular Biology Sophomore majors A (large, private) 86 (24 groups) Open-ended assessment: "What is the meaning of this representation?" Introduction to Biology I Freshman majors A (large, private) 53 Open-ended assessment: "What is happening at the arrow?" Biological Systems I Freshman majors B (small, private) 12 Introduction to Biology II Sophomore majors C (small, private) 26 Molecular Biology Sophomore majors A (large, private) 101 Upper-level elective Junior/senior majors D (medium-sized, public) 20 Upper-level elective Junior/senior majors D (medium-sized, public) 15 Interviews: Explain the diagram, including meaning of arrows Multiple Multiple A (large, private) 20 ^a^Undergraduates from seven classes at four institutions were included in various parts of the project. No individuals were included in more than one group listed. Analysis of Concept Maps ------------------------ Data were gathered using artifacts generated from students (n = 86) in a sophomore-level molecular biology course at institution A. As described by [@B1a], an important first step for determining areas of student confusion can be identified by observing students participating in group homework assignments, problem solving, or even help sessions. In our case, three- to four-member student groups (n = 24 groups total) were asked to create concept maps (C-maps) in order to answer the focus question "What is molecular biology?" C-maps, initially developed to evaluate children\'s conceptual frameworks, are based on a model of meaningful learning in relation to science knowledge ([@B46]). They can illustrate what a student knows about a particular topic and how those concepts are utilized, integrated, and linked in students' minds ([@B45]; [@B44]; [@B39]). Identifying and understanding differences between expert--novice thinking has been an important area of research in the field of cognitive psychology ([@B17]). We found that analysis of our student-generated C-maps gave us initial insights into their mental models of the central dogma and helped us develop focused research questions for the studies that followed. We defined a depiction of the central dogma as "correct" when students used appropriate terminology (e.g., "transcription") and linked concepts or processes together in a scientifically accurate way (e.g., "tRNAs transport amino acids"). We did not, however, adhere to a rigorous definition of what a C-map should look like (e.g., correct propositional structure), since most participants had little prior experience with this tool. Our goal was merely to gain insight into student thinking, not to compare this information with other groups of students or make generalizable claims. Open-Ended Assessments ---------------------- Analysis of student-generated C-maps informed us that many biology students had a poor understanding of the central dogma but did not reveal specific details of their mental models. To gain deeper understanding of how students think about the central dogma, we conducted a formative assessment with first-year biology majors (n = 53) at institution A by showing them the representation in [Figure 1](#F1){ref-type="fig"} with the following prompt: "The central dogma is usually represented by the diagram above. What is the significance or meaning of this representation? Please explain." We used inductive strategies to analyze the open-ended descriptions generated by first-year biology students ([@B48]). This unconstrained coding strategy allowed us to develop a schema that was grounded in the data and to generate an emergent coding scheme. It also allowed us to derive explanations from student language rather than from the researchers' preliminary ideas. In the first rounds of coding, original student language was used to create a number of individual categories. After discussion and analysis, categories were further collapsed, and all responses were recoded using the new scheme (an example is shown in [Figure 2](#F2){ref-type="fig"}). This procedure was repeated until both coders were satisfied all responses were accurately represented with no redundancy. ![Example of grouping multiple student responses into a single category. Original quotes from students were initially coded into preliminary categories, and then those codes were further collapsed into final categories.](338fig2){#F2} In the next round of data collection, new open-ended assessments were designed to specifically capture student thinking about the process of transcription, represented by the linear arrow between DNA and RNA. By expanding our study population, we could find out whether these incorrect ideas were unique to inexperienced first-year students or were prevalent in other populations. Thus, students from all four institutions (A--D) were recruited for this study (n = 172, ranging from first to fourth year, see [Table 1](#T1){ref-type="table"}). As part of precourse assessments, students were given [Figure 1](#F1){ref-type="fig"} with the following prompt: "This is a representation of the central dogma. Please describe, as fully as you can, what is happening at the arrow between "DNA" and "RNA."" We were able to apply deductive strategies ([@B48]) in the analysis of the 174 new responses to determine whether our previously identified themes were consistent in the new data set. Asking students to describe the molecular processes implied by the arrows in the central dogma representation allowed us to probe more deeply into student thinking and define new conceptual misunderstandings. All open-ended responses were examined through the lens of phenomenography, a qualitative research method that allowed us to investigate how students perceive a given phenomenon ([@B6]). Phenomenography is a tool particularly suited to answering educational research questions about thinking and learning ([@B36]) and also allowed us to describe the variation of ideas, both correct and incorrect, held by students in our test population. Phenomenography falls under the theoretical framework of hermeneutics, the science of interpretation or understanding ([@B63]; [@B24]), which often follows a circular approach. This qualitative method has been used by others in the DBER field to uncover student conceptions about a particular phenomenon. For example, [@B9] used a phenomenographic approach to describe the different ways teachers in training understood the biological process of photosynthesis. In the context of chemistry learning, [@B16] used a phenomenographic approach to describe high school students' conceptions about solubility and discovered that students inappropriately apply knowledge about how materials behave at the macroscopic level to the microscopic level. For example, interview passages involving student descriptions of the molecular process of transcription were analyzed in the context of the entire interview and in the context of all other responses (written or verbal) describing "transcription." As noted by [@B15], the validity of a phenomenographic approach is achieved through categories that are distinct and exclusive, recognizable as realistic perceptions, and, finally, connected with previously described results. In the fourth round of open-ended responses, two researchers independently coded the data set and reached a Cohen\'s kappa coefficient for interrater agreement of 0.807 ([@B13]; [@B8]). After that, the investigators debated each mismatch until agreement was reached on the final coding. Student Interviews ------------------ Written results were replicated during think-aloud interviews with 20 students (first-year through third-year students) from institution A. Subjects were shown the representation of the central dogma ([Figure 1](#F1){ref-type="fig"}) and asked to explain their interpretation of the diagram as a whole, as well as any individual processes it included. During the interviews, the terms central dogma, transcription, and translation were not introduced by the interviewer. Students would only be asked to further explain the process of transcription, for example, if the term was initiated by the student, in order to find out what that term meant to the student. If students did not use technical vocabulary, the interviewer did not interject any terminology. Students were also asked to explain their understanding of the process that connects the DNA to the RNA terms in the representation. RESULTS ======= Construction of C-Maps Revealed Weak Mental Models of the Central Dogma ----------------------------------------------------------------------- After student-generated C-maps answering the focus question "What is molecular biology?" were analyzed, we found that 50% of the C-maps correctly depicted the idea of information flow, with propositions such as "transcription\[s'\] purpose is to make RNA products," "transcription requires nucleotides," or "RNA is transcripted \[sic\] into proteins by ribosomes." The students in this group integrated processes related to DNA replication, transcription, and protein synthesis and used correct terminology and linkages, as seen in the map shown in [Figure 3A](#F3){ref-type="fig"}. Almost half of the groups, though, made multiple mistakes, such as not connecting RNA with the process of protein translation, depicting transcription and translation as parallel instead of sequential events (maps in [Figure 3, B](#F3){ref-type="fig"} and [C](#F3){ref-type="fig"}), and making incorrect connections between RNA and DNA (e.g., DNA converts to RNA) or C-maps with DNA and RNA nodes never connecting. [Table 2](#T2){ref-type="table"} presents the most common mistakes and their frequencies (a single map could fall into more than one category). These findings were surprising, given the C-map activity occurred on the last day of a molecular biology course. The question of why so many students failed to connect these ideas appropriately was intriguing. We were also curious to understand how deeply students understood terminology such as "transcription" and "translation": Could students use the correct words without really understanding the underlying processes? ![Representative C-maps of central dogma drawn by molecular biology students at the end of the course. (A) Correct linking of transcription and translation. (B and C) Transcription and translation drawn as parallel, disconnected processes; (C) also shows the misconception that transcription involves conversion of DNA to RNA. (Thick gray arrows superimposed on original C-maps for emphasis.)](338fig3){#F3} ###### Themes of incorrect C-maps^a^ Category Percent of total C-maps ------------------------------------------------------------- ------------------------- RNA is not connected to the process of translation 29.2 Transcription and translation are parallel (not sequential) 21 Incorrect or missing connection between RNA and DNA 29.2 Unclear C-map 8.3 ^a^n = 24; 12 maps were coded as incorrect. A single map could fall into more than one category. Open-Ended Assessments Confirm Errors of Interpretation ------------------------------------------------------- First-year biology majors, given the canonical central dogma representation and asked to explain its meaning, provided further insight into novice mental models. After all open-ended responses were coded, 12 distinct themes of student responses emerged, three of which were considered interesting and therefore are described here. Many students used a correct technical term, such as "transcription," and then described the process incorrectly. Thus, we felt that we could not assess the meaning of the word "transcription" when it was not explained further. In later work, we were more careful to elicit student interpretation of terminology and asked students specifically not to use these technical terms. Given the lack of molecular understanding by high school students described in the literature, it is not surprising that less than 10% of the students described the central dogma in the context of genetic information or information flow (see [Table 3](#T3){ref-type="table"}). Two additional themes suggest conceptual misunderstandings not yet described by the literature. In the first theme, students described RNA as if it were a participant in rather than the product of transcription. In the second theme, students described a transformation of one molecule to another, suggesting that DNA was converted, changed, or transformed into RNA during the transcription process. The language choices made by these students demonstrate very poor understanding of the processes involved in genetic information flow. Our results also suggest that the canonical representation of the central dogma adds confusion, not clarity, in understanding these processes (see excerpts below). ###### Freshman responses to open-ended assessment question^a^ Category Sample quotes Frequency ------------------------------------------------ -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ------------------- Flow of genetic information This represents the path of the info stored in molecules like DNA ... The info in DNA can be passed on to RNA molecules, which in turn actually execute the code for proteins. 9.4% (correct) Transformation of one molecule to another DNA makes DNA which becomes RNA which becomes protein 20.8% (incorrect) DNA is in the nucleus, it gets converted into RNA, base pairs are changed because the protein that makes amino acid can only use RNA. This means that DNA replication happens and the DNA is then turned into RNA and the RNA is then used in proteins. RNA exists before the process and/or drives it RNA can read the DNA and code for amino acids 20.8% (incorrect) RNA is a messenger that copies parts of DNA and codes for proteins. ^a^During the analysis of responses to a query about the meaning of the central dogma, three important categories were noted (one correct and two incorrect). Although various other responses were given, these three types were striking for their frequency. The Transcription Arrow Is a Persistent Source of Confusion ----------------------------------------------------------- Because much of the student confusion seemed to center around the process of transcription, which is represented by a single arrow in the central dogma representation ([Figure 1](#F1){ref-type="fig"}), we refined our research question to "What do students think the transcription arrow represents?" and expanded our study population to more advanced students at several institutions ([Table 1](#T1){ref-type="table"}). We assumed that an expert would view the arrow between DNA and RNA in the diagram as a representation for the process of transcription---the synthesis of a new RNA (or mRNA) molecule that is complementary to one strand of DNA. Unfortunately, about one-third of students responded with only a single term (usually "transcription" but occasionally an incorrect term such as "translation"), even though they were explicitly asked to explain any technical terms used. In those cases, it was not possible to determine what that term meant to the student. Of the remaining 128 responses, only 30% percent of students stated that a new molecule of RNA was being created. A few students crafted in-depth explanations that demonstrated a clear mental model of transcription, but others used such ambiguous language that it was difficult to interpret their meaning. In those cases, a student may have understood the underlying concept or may just have known the jargon associated with this context. As shown in [Table 4](#T4){ref-type="table"}, 20% of students indicated that the arrow was representative of a transformation from one molecule to another; just as we observed in the first-year population, in all the classes that were queried, at all institutions and levels. The other major category from the previous work, RNA exists before transcription and/or drives it, was also present in the new data set. We found that 16% of students described a scenario in which RNA existed before the process of transcription began and thus was able to be actively involved in the molecular process. These types of statements were given by students in all classes except the upper-level electives, where numbers were small (n = 20 and 15). ###### Student explanations of the central dogma from students at four different institutions, across all levels of undergraduate study^a^ Category Example Frequency ------------------------------------------------ ---------------------------------------------------------------------------------------------------------------------------------------- ----------------- DNA is copied or carries information The DNA is providing a template for the RNA to form off of. 24% (correct) A new molecule of RNA is being created Transcription. DNA is used as a template to create an RNA molecule, which is single-stranded, to be used in translation 30% (correct) Transformation of one molecule to another Transcription: the process of turning a section of the double-stranded DNA into a piece of single-stranded RNA using certain proteins. 20% (incorrect) RNA exists before the process and/or drives it transcription occurs at \#2 as the DNA transfers information to mRNA 16% (incorrect) DNA is a "template" (used the term only) DNA acts as a template for RNA. 6% (ambiguous) DNA is "transcribed to RNA." DNA is transcribed to RNA. 9% (ambiguous) DNA is "transcribed into RNA." DNA is transcribed into RNA. 23% (ambiguous) ^a^n = 128. Some responses fell into more than one category. Some responses were considered ambiguous because the student did not explain the meaning of a key technical term. Interviews Confirm Existence of Student Difficulties with the Central Dogma --------------------------------------------------------------------------- Results from the open-ended responses were confirmed during think-aloud interviews as subjects were asked to explain their understanding of the process(es) that connect the DNA to the RNA and RNA to the protein terms in the central dogma representation ([Figure 1](#F1){ref-type="fig"}). Examples of students describing the "transformation" model are given below. Sarah: The result is an RNA strand.Interviewer: What happens to the DNA strand?Sarah: The DNA strand is split into RNAInterviewer: Can you try to explain the entire figure \[[Figure 1](#F1){ref-type="fig"}\] from start to finish without using the words "transcribed" or "translated"?Steve: Ok. Um. DNA has to be taken from its double-stranded form to---and converted to RNA, which is converted to proteins, which encode for different functions in the body.Interviewer: Describe to me what this figure means to you ... if you've seen it before, what do you think the big picture is here?Cory: I mean it seems like since you made the arrow (points to the first circular arrow) like that it feels like DNA is a replicating process. Um---and then I'm guessing it\'s more of a---to me it\'s a reverse process because protein is made up of, I mean RNA is made up of protein and then RNA is what makes up DNA. I think. Cory repeated his idea that "RNA is made up of protein" and "RNA is what makes up DNA" several more times during the interview. To clarify his thinking about the arrows in the figure, the interviewer sketched a generic diagram of a metabolic pathway "A→B→C" and asked Cory whether he thought it was a comparable diagram. He agreed this new diagram was the same as [Figure 1](#F1){ref-type="fig"}, suggesting that he interpreted the central dogma representation as a series of chemical reactions. The model of RNA existing before transcription was espoused by another subject in an interview. Libby: Yeah, oh yes, I have \[seen a diagram like [Figure 1](#F1){ref-type="fig"}\]. It\'s transcription or something with a "trans" in the beginning. There\'s, like, three of them, and I think it\'s transcription where you have the DNA and then the RNA comes and it transcribes so the RNA knows what protein to make, from the DNA.\[...\]Interviewer: Okay, I labeled the arrows 1, 2, and 3. If we just focus on arrow 1, can you tell me what you think is being represented by that arrow or what is going on in that process?Libby: Okay. I think it means, like, well, DNA in the beginning has to unzip because otherwise RNA can\'t get in. So I think I'm guessing that what\'s \[sic\] the little circle arrow thing means because it has to unzip so the RNA can get in there and then attach to one side of the DNA and then transcribe from that.Interviewer: Okay. What about arrow 2?Libby: I'm just assuming that arrow 2 is DNA allows RNA to get in, like, that\'s the process that it has to go through. DNA has to unzip first and then the RNA comes in and then the protein comes in so, it\'s just, like, step by step by step.\[....\]Libby: I think arrow 3 represents the whole process of the RNA, like, transcribing all the amino acids together and making it into a protein so, like, the arrow 3 just represents that process. RNA makes the amino acids and then it makes the protein. Libby consistently described RNA as an entity that already existed in the system and an active participant in various processes through her language usage such as, "RNA gets in there" or "RNA comes in" or "RNA makes ..." throughout the interview. At another point, she was asked to explain the origin of the RNA in her model. The student responded with surprise to this question. Interviewer: And how does, um, where does that RNA strand come from? You said the DNA unzips and RNA strand can match up with it. Where does that RNA strand come from?Libby: That\'s a very good question! Um, I'm assuming it just comes from somewhere in the cell. Maybe leftover parts? I---I have actually never thought about that. Analysis of the responses in this data set revealed that using correct terminology was not necessarily linked with correct understanding of the molecular process of transcription. Forty-four percent of students (20 out of 45) who answered the open-ended survey question with one of the two conceptual misunderstandings also used the term "transcribe" or "transcription" in their explanations. Although the technical language was correct, the underlying mental models of the molecular process were not. We highlight this point, as 23% of students who responded to the open-ended question described the transcription arrow by writing the phrase "DNA is transcribed into RNA," while 9% of students answered the question by writing "DNA is transcribed to RNA." Although neither one of these statements is technically incorrect, we cannot know for certain what these student answers mean. When a student writes the phrase, "DNA is transcribed into RNA," does he or she mean that a new molecule of RNA is synthesized using a DNA template or does he or she mean that DNA is converted into RNA? This cannot be determined, because correct terminology does not necessarily correlate with understanding. DISCUSSION ========== Through this work, we have uncovered novel misconceptions concerning how students think about information flow as it pertains to the central dogma of molecular biology. We feel that it is important to disseminate these findings to instructors and textbook authors, because they must be aware of these ideas in order to help students confront them. Research in cognitive science demonstrates that deep learning requires dynamic reorganization of mental structures; misconceptions must be replaced with true conceptions ([@B32]; [@B49]; [@B25]). Instructors cannot simply add more information to their students' minds, especially if they are not aware of what their students are thinking about. [@B56] remind us that effective instruction happens only when educators gain insight into student thinking, insight we attempt to provide in this work. Our analysis revealed several interesting findings: 1) Students are not primed to think about "information" when presented with the canonical figure of the central dogma, and 2) misconceptions about the central dogma were exposed when students had to describe the meaning of an arrow in the central dogma representation. Our work demonstrates that the arrow representing transcription in the typical central dogma figure seems to miscue many biology students: in cognitive terms, the arrow does not prime them to think about molecular mechanisms or even information flow. When asked to describe the significance of the arrow, some biology students think of the arrow as a chemical conversion similar to the arrow they might see when studying a metabolic pathway such as glycolysis ([Figure 4A](#F4){ref-type="fig"}). This is the wrong cognitive resource, which could interfere with meaningful learning. In other words, students who inappropriately apply the representation of a chemical reaction to the central dogma might conclude that DNA gets transformed through chemical processes into RNA during transcription. Because we found evidence of this misconception in all levels of students (first year to advanced), we conclude that this incorrect idea is robust and not just something that inexperienced students say. ![Examples of biological representations that include arrows. (A) The first steps of the metabolic pathway of glycolysis. (B) Electron transport in the mitochondrial membrane.](338fig4){#F4} Other students seem to interpret transcription as a transfer of material between two existing entities, DNA and RNA---an incorrect model of information movement analogous to the movement of electrons by respiratory chain proteins during aerobic respiration ([Figure 4B](#F4){ref-type="fig"}). One of the major flaws of this model is that RNA must already exist before the process of transcription begins so that "information" or "material" can be transferred to and from DNA and RNA. These students completely miss the idea of new RNA synthesis and seem to be thinking about information as an entity or particle, similar to what [@B33] observed among high school students trying to explain the nature of genes. In the case of the central dogma, we suggest that the arrow representation is too vague and can mean too many things to students. We found that students who do not have a solid understanding of the molecular mechanisms used during information flow see the arrow mainly as a sign for a chemical conversion or as a signal for a physical transfer of something. Sometimes students in our study population misinterpreted the symbolism of the arrow itself rather than the mechanism of transcription. For example: "DNA acts a template as production of RNA. The arrows show how the genes are actually used." "DNA is a template for RNA so the arrow between then is representative of base-pairing with thymine being substituted with Uracil to create RNA" "The Genes from DNA is what defines the structure of RNA. What the arrow could mean is a specific strand of DNA that is used in RNA." Arrows are not found only in biology representations, they are also used extensively in the field of organic chemistry to demonstrate a variety of concepts. Unlike traditional college biology courses, though, students in an organic chemistry course are given explicit directions on how to use and interpret arrow symbols that will be encountered during the course. A typical organic chemistry textbook explains that chemical diagrams are good for showing the positions of atoms but not electrons, because electrons are not solid particles with a singular position in place and time ([@B28]). Students are then presented with explanations and diagrams of a correctly drawn curved arrow ([Figure 5A](#F5){ref-type="fig"}) that is used in the field of organic chemistry to represent the movement of electrons in different contexts. Later, students are introduced to full-headed arrows that represent actual mechanisms ([Figure 5B](#F5){ref-type="fig"}), while partial-headed or "fishhook" arrows ([Figure 5C](#F5){ref-type="fig"}) indicate the shift of a single electron. The double-arrow structure in [Figure 5D](#F5){ref-type="fig"} is the symbol for equilibrium. Organic chemists are able to convey scientific concepts to one another and to their students using arrow symbolism, because there is an accepted and universal language that everyone in the field follows. Biologists, on the other hand, do not seem to subscribe to a given set of scientific representations---likely confusing for the nonexpert! ![Different arrow representations used in organic chemistry. Arrows are used to represent (A) movement of electrons, (B) mechanisms, (C) single electron shift, and (D) equilibrium.](338fig5){#F5} While representations are crucial for communicating science, language is just as important. Students will, unfortunately, encounter imprecise language in textbooks, tutorials, and classrooms that may confirm, rather than refute, their misconceptions. For example, in an online tutorial written about the central dogma (<https://cm.jefferson.edu/learn/dna_and_rna.html>), the author writes: "The central dogma of molecular biology is "DNA makes RNA makes protein." This general rule emphasizes the order of events from transcription through translation and provides the basis for much of the genetic code research in the post double helix 1950s. The central dogma is often expressed as the following: "DNA makes RNA, RNA makes proteins, proteins make us."" We suggest the author of this tutorial really believes that "DNA makes RNA," but the choice of language is potentially confusing and may also solidify, not refute, certain weak mental models of the central dogma. An expert reading the passage would be able to look beyond the literal meaning of the word "makes" to envision the complex processes that underlie the synthesis of RNA, but a novice might interpret the word "makes" in a very literal sense and infer that DNA is the driver, not the template, in the process. Therefore, it is crucial that we, as educators, are careful about our language with students and demand that students be equally precise. Without such rigor, we cannot evaluate their mental models or prevent the creation of new misconceptions. As [@B64] pointed out, "knowing the facts and doing well on tests of knowledge do not mean that we understand." Many biology education research (BER) practitioners have echoed this observation in their own work and have made a concerted effort to avoid questions and responses based solely on student recognition of correct vocabulary terms in the development of biology concept assessment tools ([@B7]; [@B61]; [@B29]; [@B59]). Our findings from open-ended responses and interviews revealed that students can recognize and use correct terminology while still employing faulty mental models of information flow. This suggests that classroom assessment strategies must probe students to do more than come up with correct vocabulary terms. Students could be asked, for example, to explain information flow or create C-maps in the context of the central dogma without using technical terms such as transcription/transcribe or translation/translate. We have begun to use this strategy with our own classes, and preliminary results suggest that taking away the scientific jargon is a good way to elicit true mental models of students and begin discussion of scientific language and underlying concepts. Instructors might also work with their students to trace matter (including nucleotides, polymerases, etc.) through each major step of the central dogma, similar to what [@B12] demonstrated with geoscience students trying to understand movement and transformation of water in dynamic Earth systems. The student-generated C-maps ([Figure 3](#F3){ref-type="fig"}), which were the catalyst for this study, actually revealed very little of what students know about information flow. What did the students mean, for example, when they linked nodes containing the terms "DNA" and "RNA" with the linking word "transcription"? Without further probing, it is not possible to know. Thus, future work will incorporate the findings from this study into a new concept assessment that specifically focuses on information flow. As part of that project, we will also investigate student understanding of the process of protein translation. The development and dissemination of more concept assessment instruments focusing on central dogma topics may help the BER community identify learning progressions for a number of related topics. The [@B47] describes learning progressions as descriptions of increasingly sophisticated ways to think about or understand a topic. The coordination of assessments, classroom activities, and instructor preparation on any number of topics could potentially be guided by these learning progressions ([@B3]). For example, The Environmental Literacy Project at Michigan State University (<http://edr1.educ.msu.edu/environmentallit>) has made great strides in the development and dissemination of learning progressions in the context of environmental science. Because human endeavors greatly impact natural and environmental systems of our planet, there is a dire need to educate all citizens, so they may take part in decisions about environmental issues and policies ([@B23]). The BER community might look to the Environmental Literacy Project for guidance in the development of learning progressions for understanding concepts related to the central dogma. As advances in biomedical knowledge and technology continue to outpace our current education system, and direct-to-consumer genetic testing companies make genetic analysis affordable and accessible, it is essential for all citizens to be genetically literate and make informed decisions concerning healthcare and privacy issues. The growing body of literature on student understanding of information flow suggests the BER community could be poised to undertake such an endeavor. We thank participating faculty members who provided data by giving the assessments to their students, and Dr. Thomas Kim for critical feedback on the manuscript.
Monitoring psychosocial stress at work: development of the Psychosocial Working Conditions Questionnaire. Many studies on the impact of psychosocial working conditions on health prove that psychosocial stress at work is an important risk factor endangering workers' health. Thus it should be constantly monitored like other work hazards. The paper presents a newly developed instrument for stress monitoring called the Psychosocial Working Conditions Questionnaire (PWC). Its structure is based on Robert Karasek's model of job stress (Karasek, 1979; Karasek & Theorell, 1990). It consists of 3 main scales Job Demands, Job Control, Social Support and 2 additional scales adapted from the Occupational Stress Questionnaire (Elo, Leppanen, Lindstrom, & Ropponen, 1992), Well-Being and Desired Changes. The study of 8 occupational groups (bank and insurance specialists, middle medical personnel, construction workers, shop assistants, government and self-government administration officers, computer scientists, public transport drivers, teachers, N = 3,669) indicates that PWC has satisfactory psychometrics parameters. Norms for the 8 groups were developed.
This post is a transcript of Reverse the ‘Verse: Episode 103 Summary, material that is the intellectual property of Cloud Imperium Games (CIG) and it’s subsidiaries. INN is a Star Citizen fansite and is not officially affiliated with CIG, but we reprint their materials with permission as a service to the community. INN edits our transcripts for the purpose of making the various show participants easier to understand in writing. Enjoy! Incomplete Transcripts Show is live! It’s just Jared and Tyler this week. Reverse the ‘Verse is CIG’s weekly Informal livestream with the fans. Tylers week: A lot of ATV recording prep. Managed to get a little bit of sleep and learned a lot from the new processes for video content. If you haven’t been watching ATV recently. Every week has featured a different studio to focus on for the show. First was Los Angeles, second was Foundry 42 UK, yesterday was Austin and last will be Frankfurt. They’ve been wanting to shake things up a bit and bring about a more refined experience to the backers as well as to the public to show them what CIG is really about. Tyler: Very excited to keep making the shows better and better. Sometimes they had to use a paint roller and string as a makeshift boom mic as an example from where they’ve come. This change for video content doesn’t just affect the community team, but the entire studio as they have to get used to daily filming and integrating it into their routines. This doesn’t take away from their development time, but finding creative ways to bring about harmony to this new process. 10 for the Chairman wont be coming back, but they’re experimenting with a new format that’s similiar, but shows off more of the game. Chris loved 10 for the Chairman, but wanted something fresh for backers. They may rebrand Around the ‘Verse as something else depending on the changes coming to the show in the future. They also may have Reverse the ‘Verse in other studios, possibly Frankfurt with Brain Chambers. HYPE! They don’t want LA to be the focal point as other studios do as much if not more in terms of production as LA does. Tyler is looking down a lot because he can reach a pokestop in the room. Ben is home sick today. He’s got the flu. Alexis will join shortly, she’ll talk about the new sale that’s going up today. Also this week was the ‘final’ release of the Ballad of Big Benny’s. It’s a 3 minute long music video based on the original 30 second Big Benny’s audio-clip. The song tells a bit of a story. It was in AtV 100, and it’s on CIG’s Youtube. Also on AtV was Tony Zurovec. They recorded more than they aired with everyone, with Tony Z, with the Animation team, etc… that they’ll put out there eventually. Tony did everything in one take. He knew what he wanted to say and just talked. Common trait at that level, between the likes of Tony, Chris, Brian, and Erin. When you know that much, you have a lot to talk about. AtV also checked in on Emre Switzer, who’s doing the lighting for Grim Hex. They’ve actually made major changes to lights themselves; lights and their emisisons are now a single entity. First saw that in the video of the Starfarer at night a few weeks ago. New people showing up. We’ve got Justin and Alexis now. Alexis is here with a Merch update. Right after the show, Big Benny’s t-shirts will be available in the store. Subscribers who pre-order will also get a patch. They’ll be 25$, includes shipping, same price for subscribers and non-subscribers. Shirts are all-cotton. The shirts are a limited quantity and a limited number of sizes, large through 4xl. They’ll do another future run based on sales. Subscriber flair is also out today. Flair this week is a space plant, but it won’t be in-hangar till 2.5 is out. Tyler just caught a Wartortle. And we’re now into QA time. Questions will be taken from the RSI chat, not twitch chat. [The mobiGlas found a new look from the original design, will the exclusive omniGlas find similar changes?] The functionality will stay the same, the difference in the physical appearance. [Will you be able to unequip the mobiGlas?] They’re not sure, probably but not at the point to make the decision yet. [Will the RTV format come back with all the people around the table?] They don’t know. There’s a scenario on the table where RTV and ATV go away. New shows would replace them, similar format. Thursday would rotate between the studios so each studio is featured in one episode and that’s something they for sure will do. Fridays show will stay similar, but basically Jared or Ben or Tyler would be in the small window and in the big window would be Brian Chambers, or Erin Roberts, Tony Zurovec, etc. Tyler: Apparently QA has been testing about making the Big Benny’s machine work in persistence. The logic there is that if the Big Benny’s machine works, a lot of other items can work as well so Big Benny’s has created test cases for them. Luke Pressley in the UK, head of PU design, Disco sends him messages every once in a while about things people are doing in the PU. It’s not just about taking info from Devs and giving it to the community, it’s also about taking what the community are saying and doing and making sure the Devs know about it. [Updates for CAT?] Not yet. We’ll see updated specs when it becomes hangar-ready. There are three stages of ship updates. Concept, hangar, flight. Hangar-ready stage is the next stage, it’s when we’ll see the updates to the CAT. Up until then, things can still change. [Will Benny’s machine eventually dispense noodles?] Machines will eventually be usable, and with Subsumption NPC’ll interact with the environment, using useables. One of the ones they’ve done is the Big Benny’s machine and the Pips machines being used. Once you’ve set it up for one machine, you can have an array of machines that can all be interacted with. [With realisation we’ll get ships quickly from SQ42 development, any idea what those ships’ll be?] Yes. [Jalopy ship in pipeline?] No They try to get info from the horse’s mouth as much as possible. Anything SQ42 related, while they have some info, it’s better for it to come from the guys in the UK. They’ll save SQ42 questions for shows once they start rotating them to the UK. [2.5 content locked?] No. They have the plan, they know what they want in it, but it’s not locked yet. Just because it’s not feature locked doesn’t mean the team aren’t confident with what they’re putting in. There are loose ends to wrap up, but it’s more about how fast they get things working together. Just because it’s not feature locked doesn’t mean it’s going to be late. [2.5 before Gamescom?] Disco can’t speak to it, but he knows that’s the goal. It’s looking really good according to Tyler. [Who shot Tony Z interview?] William ‘Soulcrusher’ Leverett [Digital t-shirts from last AtV as merch?] No plans as physical merch, but it’s not beyond the realm of possibility that if there’s something in-game that sells a lot, maybe they could do it as physical merch. [Updates on HOTAS?] None yet. Still waiting for prototype. [Argo sale price?] Don’t have it yet, still some talk about the Argo sale price. They’ll announce it asap, they’ll know it at least a week before the sale. [What use will the Argo have?] They’re discussing that internally as well. One of the things that Disco’s excited about is seeing what community does with it that they didn’t intend. [Update on what we’ll be able to purchase in-game next?] New clothing. Until 2.5 is content locked, they can’t commit to anything though. [Talk more about Cargo that Tony Z talked about?] Can’t really. It’s part of why they’re gonna rotate the shows so we can hear it from Tony Z directly. [Will Phoenix still have larger guns than other variants?] That’ll be determined when they do the rebuild, but Disco hasn’t seen anything that’d suggest that it’ll change. [Evocati testers?] They’re looking to add more towards the end of the summer, but it’s mostly algorithm. Participation on the issue council is a big factor and not just submitting fillers, but meaningful contributions. [Will reduced patch size be ready for 2.5?] Probably not. With the initial rollout they’re gonna test it internally first, cause devs have to get multiple new builds per day. Once they’re confident with it internally, they’ll roll it out. [Adoption numbers for MFA?] On Tuesday they rolled out MFA, came from Turbulent. Long-needed feature for SC. They don’t have adoption numbers on it yet, but they’re very pleased with it. If you haven’t signed up for MFA, do so! [Non lethal weapons in FPS gameplay?] Possibly, they’re looking at it. There’s a feature on the weapons in ATV, so no promises, but look to next week for that. [Is Brian Chambers coming to Gamescom?] Yes! [Will the mobiGlas get pokemon Go?] No. [Will Polaris be able to dock an Argo?] Disco can’t see why not. Until they’re both built it’s impossible to be 100% sure, but Disco’s first answer was ‘absolutely’, so it’s probably around 97% likely. [Don’t go back to old AtV] The new AtV is here to stay, it just might have a different name. And they’ll continue to improve as they go. [Grimhex a safe zone?] They’re still going back and forth, they’re doing internal testing. Not finalised yet. More Grim Hex info coming in next week’s AtV. [List of CIG people going to Dragoncon?] They’re not doing Dragoncon this year. The Euro trip is the higher priority, especially with the new video stuff they’re doing. They’re exploring what they can do, how to improve things, etc…
Sofa Buy Sofa Set Online - UAE Buying a sofa can be overwhelming. Picking the right sofa for your living space includes balancing functionality with aesthetics, keeping details like dimension, price and quality in mind. Choosing a sofa is a commitment and an investment – you need to be content with your choice for quite a long time to come. At Danube Home, we organize our range of sofas and sofa beds logically, offering styles that reflect the latest interior trends from Dubai and abroad. We additionally give point by point information so that you can settle on an informed decision. With the convenience, decision and information that Danube Home offers, buying sofas online should actually be easier than buying them anywhere else. Shop furniture online from danubehome.com in just a single click and experience most elite scope of furniture products. You can likewise benefit the spectacular discounts with free home delivery in UAE and cash on delivery. Simply visit our online store to know more about our Furniture Products. Elite Collection of Sofa Sets on danubehome.com Danube Home gives you variety of ideas for your living room. It presents you a plenty of sofa set designs. The designs you get are arabic styles, vintage set and cutting edge modern designs. Pick the right material and size for your set. Get a recliner or luxurious sofa according to your comfort. You ought to choose the particular case that will suit your style completely. Other than these, the wooden sofa sets are likewise extremely popular. Get the best furniture shopping experiences while buying from Danube Home online. Browse an extensive variety of online recliners, two seater couches, three seater couches, sofa sets, sofa cum beds and L shaped sofas designs for your living room from our website danubehome.com
Architectural metallic meshes are generally used in commercial and business environments to provide elegant wall panels, doors and other surfaces whenever an aesthetic appearance of polish and prestige are of primary importance. Architectural mesh is also an excellent choice for high contact areas, such as the interior walls of elevator cabs, escalator walls, and sales and reception areas, because it is generally scratch, dent and corrosion resistant. As such, architectural metallic mesh maintains a stunning appearance with minimal maintenance. Woven into panels from brass, stainless steel, copper, and/or other desired metals or alloys, architectural mesh offers a richness of texture, pattern and color that cannot be duplicated by any other material. Architectural mesh can also be polished, finished and combined with different background colors to create a custom look and configuration. Depending upon the chosen weave, the interstices or apertures between the weft or fill wires and the warp wires may allow light to pass through the architectural mesh. Alternatively, if the weave is tight and the wires are more closely adjacent to one another, the passage of light through the mesh will be selectively prevented. Accordingly, as the requirement for incorporating energy savings into building design increases, and hence the need for architecturally acceptable sun shading or screening, architectural mesh offers a variety of options that can meet the shading needs while still maintaining architectural requirements. Thus, it would be desirable to provide system for reliably and conveniently applying an architectural mesh product to a building wall, so as to create the desired sun shading without detracting from the aesthetic appearance of the wall.
Biography The music of Heitor Villa-Lobos is known for its characteristic nationalism, driving rhythms, and original instrumentation. He was trained as an autodidact opposed to academic instruction, his music grew in a completely independent and individual fashion. Villa-Lobos began studying music at an early age, when his father, a worker at the National Library and an amateur musician, taught him to play cello, viola, and guitar. These earlyRead more influences later became evident in the orchestration of some of his more prominent works. Although he intended to enter school to study medicine, Villa-Lobos soon found that he preferred spending time with the local popular musicians, becoming familiar with the various musical styles native to Rio de Janeiro's street and night life. Among other skills, he learned to improvise guitar melodies over the "choro," a popular instrumental genre of the time, which lent Villa-Lobos the effortless Latin nationality so strongly present in his music. From the ages of 18 to 25 he traveled extensively throughout Brazil and the African-influenced Caribbean nations, collecting themes and assessing the major style characteristics of the local musics. It was also during this time that Villa-Lobos composed his first major compositions, most notably his Piano Trio No. 1. When he returned to Rio de Janeiro in 1912, Villa-Lobos briefly attempted to receive a more formalized education, but his personality and musical practice proved ill-matched with the academic establishment and, although he made important connections with the faculty, he soon left classes. He spent the next ten years composing and playing freelance cello in cafes and cinemas to earn a living. He eventually gained national recognition and a fair sum of government funding with the premiere of his Third Symphony, "A guerra," the first part of a symphonic trilogy commissioned by the Brazilian government to commemorate World War I. From 1923 to 1930, Villa-Lobos found himself centered in Paris, where he was a huge success, his music being widely published and frequently performed. He eventually returned to Brazil, however, becoming one of the most esteemed artists of the new Nationalist regime, which lasted until 1945. During the 1930s, Villa-Lobos involved himself deeply and enthusiastically with public music education, once again traveling throughout Brazil to offer his services as a teacher and school coordinator. In 1945, his passion reached the ultimate fruition when he founded the Brazilian Academy of Music. He spent the last ten years of his life traveling and conducting, primarily in New York and Paris. Read less Formats & Featured Sign up now for two weeks of free access to the world's best classical music collection. Keep listening for only $0.0/month - thousands of classical albums for the price of one! Learn more about ArkivMusic Streaming
A Highly Efficient Diversification of 2-Amino/Amido-1,3,4-oxadiazole and 1,3,4-Thiadiazole Derivatives via Reagent-Based Cyclization of Thiosemicarbazide Intermediate on Solid-Phase. A 2-amino/amido-1,3,4-oxadiazole and 1,3,4-thiadiazole library has been constructed on solid-phase organic synthesis. The key step on this solid-phase synthesis involves the preparation of polymer-bound 2-amino-1,3,4-oxadiazole and 1,3,4-thiadiazole core skeleton resin by cyclization of thiosemicarbazide with EDC·HCl and p-TsCl, respectively. The resulting core skeleton undergoes functionalization reaction with various electrophiles such as alkyl halides, and acid chlorides to generate N-alkylamino and N-acylamino-1,3,4-oxadiazole, and 1,3,4-thiadiazole resin, respectively. Finally, the 2-amino and 2-amido-1,3,4-oxadiazole and 1,3,4-thiadiazole library was then generated in good yields and high purities by cleavage of the respective resin under trifluoroacetic acid(TFA) in dichloromethane(DCM). The constructed library shows reasonable, oral bioavailability drug properties as determine by using the Lipinski's Rule and similar parameters.
Q: Can I use an air gap faucet as a standard faucet? I recently replaced my RO filter system with a simpler water filter system. I did not get a new faucet since I figured that I could just use the existing one that was installed with my RO system. Once I started tinkering around, I discovered the 2 extra drain hoses on my RO faucet (an air gap faucet). The faucet looks like this: https://www.freedrinkingwater.com/support/wp-content/uploads/all-ro-faucet-installation-figure1.jpg Referencing the image, I disconnected the orange line and just left it uncapped under my sink. I left the black line to the drain saddle where it was. I plugged my new clean water line where the blue line is in the above image. As I understand the 2 drain lines in the air gap faucet just connect to each other inside the faucet and to a vent hole in the faucet base. Is this a bad idea? Are there any possible problems I should be aware of? I'd rather not replace the faucet because it's in a really tight spot that's hard to access. Any insight would be appreciated. A: I think the air gap in an air gap faucet is separate, mechanically speaking, from the actual faucet. It's just in the same mechanism because both need to be in a similar physical location. Leaving both the drain and waste lines disconnected should be appropriate, and shouldn't give you any surprises. To expand on that: The air gap in a RO system exists because it needs to flush itself with water to clean up every so often. That water is waste water, and is not drinking quality. So, it goes down the drain. The air gap has the same purpose as on a dishwasher; to ensure that any blockages result in water overflowing into the sink instead of backing up or damaging any equipment. (Note the overflow hole in the faucet.) Because this mechanism relies on gravity, it needs to be placed above the level of the drain. None of this interacts with the actual faucet, but the faucet also goes next to the sink, so you might as well reuse the hole. You could have a dishwasher-style air gap and a regular faucet, and that would also work.
# DO NOT EDIT THIS FILE. This file will be overwritten when re-running go-raml. """ Auto-generated class for User """ from six import string_types from . import client_support class User(object): """ auto-generated. don't touch. """ @staticmethod def create(kwargs): """ :type name: string_types :type username: string_types :rtype: User """ return User(kwargs) def __init__(self, json=None, **kwargs): if json is None and not kwargs: raise ValueError('No data or kwargs present') class_name = 'User' data = json or kwargs # set attributes data_types = [string_types] self.name = client_support.set_property('name', data, data_types, False, [], False, True, class_name) data_types = [string_types] self.username = client_support.set_property('username', data, data_types, False, [], False, True, class_name) def __str__(self): return self.as_json(indent=4) def as_json(self, indent=0): return client_support.to_json(self, indent=indent) def as_dict(self): return client_support.to_dict(self)
Red Lion Mismatched MX Pink Ribbon Socks. Whoever said your socks have to MATCH? be ORIGINAL!!! Each Pair comes as a Mis-match. Help show your support for Breast Cancer Research by wearing these great Pink Ribbon socks!
package edu.stanford.bmir.protege.web.client.primitive; import com.google.common.collect.Lists; import com.google.common.collect.Sets; import com.google.gwt.core.client.GWT; import com.google.gwt.user.client.ui.SuggestOracle; import edu.stanford.bmir.protege.web.client.library.suggest.EntitySuggestOracle; import edu.stanford.bmir.protege.web.client.library.suggest.EntitySuggestion; import edu.stanford.bmir.protege.web.shared.DataFactory; import edu.stanford.bmir.protege.web.shared.PrimitiveType; import edu.stanford.bmir.protege.web.shared.match.criteria.CompositeRootCriteria; import edu.stanford.bmir.protege.web.shared.match.criteria.EntityMatchCriteria; import org.semanticweb.owlapi.model.EntityType; import org.semanticweb.owlapi.model.OWLLiteral; import javax.annotation.Nonnull; import javax.inject.Inject; import java.util.LinkedHashSet; import java.util.List; import java.util.Optional; import java.util.Set; /** * Author: Matthew Horridge<br> * Stanford University<br> * Bio-Medical Informatics Research Group<br> * Date: 19/01/2013 / public class PrimitiveDataEditorSuggestOracle extends SuggestOracle { private EntitySuggestOracle delegate; private Set<PrimitiveType> allowedPrimitiveTypes = new LinkedHashSet<>(); // private FreshEntitySuggestMode mode; private FreshEntitySuggestStrategy freshEntityStrategy = new NullFreshEntitySuggestStrategy(); private Request lastRequest = null; @Inject public PrimitiveDataEditorSuggestOracle(EntitySuggestOracle delegate, @EntitySuggestOracleSuggestMode FreshEntitySuggestMode mode) { this.delegate = delegate; // this.mode = mode; allowedPrimitiveTypes.add(PrimitiveType.CLASS); allowedPrimitiveTypes.add(PrimitiveType.NAMED_INDIVIDUAL); } public void setCriteria(CompositeRootCriteria entityMatchCriteria) { delegate.setCriteria(entityMatchCriteria); } public void setFreshEntityStrategy(FreshEntitySuggestStrategy strategy) { this.freshEntityStrategy = strategy; } public void setAllowedPrimitiveTypes(Set<PrimitiveType> primitiveTypes) { allowedPrimitiveTypes.clear(); allowedPrimitiveTypes.addAll(primitiveTypes); Set<EntityType<?>> entityTypes = getAllowedEntityTypes(); delegate.setEntityTypes(entityTypes); } private Set<EntityType<?>> getAllowedEntityTypes() { Set<EntityType<?>> entityTypes = Sets.newHashSet(); for(PrimitiveType primitiveType : allowedPrimitiveTypes) { if(primitiveType.isEntityType()) { entityTypes.add(primitiveType.getEntityType()); } } return entityTypes; } // public FreshEntitySuggestMode getMode() { // return mode; // } // public void setMode(FreshEntitySuggestMode mode) { // this.mode = mode; // } /* * Generate a {@link Response} based on a specific {@link * Request}. After the * {@link Response} is created, it is passed into * {@link Callback#onSuggestionsReady(Request, * Response)}. * @param request the request * @param callback the callback to use for the response / @Override public void requestSuggestions(Request request, final Callback callback) { lastRequest = request; delegate.requestSuggestions(request, (req, response) -> { if(req != lastRequest) { GWT.log("[PrimitiveDataEditorSuggestOracle] Ignoring stale request: " + request.getQuery()); return; } List<EntitySuggestion> suggestions = (List<EntitySuggestion>) response.getSuggestions(); if (shouldOfferCreateSuggestions(req, suggestions)) { suggestions.addAll(freshEntityStrategy.getSuggestions(req.getQuery(), getSuggestedTypesForQuery(req.getQuery()))); callback.onSuggestionsReady(req, new Response(suggestions)); } else { callback.onSuggestionsReady(req, response); } }); } private List<EntityType<?>> getSuggestedTypesForQuery(String query) { if(query.length() == 0) { return Lists.newArrayList(getAllowedEntityTypes()); } List<EntityType<?>> result = Lists.newArrayList(getAllowedEntityTypes()); if(Character.isLowerCase(query.charAt(0))) { if(result.remove(EntityType.NAMED_INDIVIDUAL)) { result.add(0, EntityType.NAMED_INDIVIDUAL); } } else { if(result.remove(EntityType.CLASS)) { result.add(0, EntityType.CLASS); } } return result; } private boolean shouldOfferCreateSuggestions(Request request, List<EntitySuggestion> existingSuggestions) { if(freshEntityStrategy.getMode() != FreshEntitySuggestMode.SUGGEST_CREATE_FRESH_ENTITIES) { return false; } if(canParseAsNumericLiteral(request)) { return false; } if(canParseAsStringLiteral(request)) { return false; } for(EntitySuggestion existingSuggestion : existingSuggestions) { if(existingSuggestion.getEntity().getBrowserText().equalsIgnoreCase(request.getQuery())) { return false; } } return true; } private boolean canParseAsNumericLiteral(Request request) { if(!allowedPrimitiveTypes.contains(PrimitiveType.LITERAL)) { return false; } OWLLiteral lit = DataFactory.parseLiteral(request.getQuery(), Optional.empty()); return !(lit.getDatatype().isString() \|\| lit.getDatatype().isRDFPlainLiteral()); } private boolean canParseAsStringLiteral(Request request) { return allowedPrimitiveTypes.contains(PrimitiveType.LITERAL) && ( allowedPrimitiveTypes.size() == 1 \|\| allowedPrimitiveTypes.contains(PrimitiveType.DATA_TYPE) && allowedPrimitiveTypes.size() == 2); } /* * Should {@link Suggestion} display strings be treated as HTML? If true, * this * all suggestions' display strings will be interpreted as HTML, otherwise as * text. * @return by default, returns false */ @Override public boolean isDisplayStringHTML() { return delegate.isDisplayStringHTML(); } }
Read More Mr Rattray was taken to accident and emergency and his injuries included a ruptured diaphragm. He was left in a 'complete state of shock' by what happened to him and suffered depression. The judge who jailed Marshall found that he had played the leading role and 'exploited' the youths to take part in the crime. The raiders had suspected the victim was "making his money from dealing drugs" and had a stash inside the property, but there was no evidence that drugs were the source of his income and the only evidence of drugs at the property had been "a few young cannabis plants". Tom Little, for the Attorney-General, argued that Marshall's jail term was far too soft, given the seriousness of the attack. And Lord Justice Davis agreed that the sentence was 'much too short', before upping the term by four years. Police investigate an aggravated burglary at Bryants Hill, St George. Daniel Marshall, 24, of Cromer Road, Eastville, has been jailed along with two boys aged under 18, who cannot be named for legal reasons. The judge pointed to the 'disturbing and indeed shocking nature of this offending'. Two Bristol teenagers, aged 16 and 15, were convicted of the same crimes as Marshall and they both got four-and-a-half years detention. Their sentences were also increased, to six-and-a-half years, by the judge, who was sitting with Mr Justice Phillips and Judge Geoffrey Marson QC.
Atom probe study of vanadium interphase precipitates and randomly distributed vanadium precipitates in ferrite. Atom probe tomography and transmission electron microscopy were used to examine the precipitation reaction in the austenite and ferrite phases in vanadium micro-alloyed steel after a thermo-mechanical process. It was observed that only in the ferrite phase precipitates could be found, whereupon two different types were detected. Thus, the aim was to reveal the difference between these two types. The first type was randomly distributed precipitates from V supersaturated ferrite and the second type V interphase precipitates. Not only the arrangement of the particles was different also the chemical composition. The randomly distributed precipitates consisted of V, C and N in contrast to that the interphase precipitates showed a composition of V, C and Mn. Furthermore the randomly distributed precipitates had maximum size of 20 nm and the interphase precipitates a maximum size of 15 nm. It was assumed that the reason for these differences is caused by the site in which they were formed. The randomly distributed precipitates were formed in a matrix consisting mainly of 0.05 at% C, 0.68 at% Si, 0.03 at% N, 0.145 at% V and 1.51 at% Mn. The interphase precipitates were formed in a region with a much higher C, Mn and V content.
Q: Scala: Unspecified value parameter evidence$3 I've looked around and found several other examples of this, but I don't really understand from those answers what's actually going on. I'd like to understand why the following code fails to compile: val df = readFiles(sqlContext). withColumn("timestamp", udf(UDFs.parseDate _)($"timestamp")) Giving the error: Error:(29, 58) not enough arguments for method udf: (implicit evidence$2: reflect.runtime.universe.TypeTag[java.sql.Date], implicit evidence$3: reflect.runtime.universe.TypeTag[String])org.apache.spark.sql.UserDefinedFunction. Unspecified value parameter evidence$3. withColumn("timestamp", udf(UDFs.parseDate _)($"timestamp")). ^ Whereas this code does compile: val parseDate = udf(UDFs.parseDate _) val df = readFiles(sqlContext). withColumn("timestamp", parseDate($"timestamp")) Obviously I've found a "workaround" but I'd really like to understand: What this error really means. The info I have found on TypeTags and ClassTags has been really difficult to understand. I don't come from a Java background, which perhaps doesn't help, but I think I should be able to grasp it… If I can achieve what I want without a separate function definition A: The error message is a bit mis-leading indeed; the reason for it is that the function udf takes an implicit parameter list but you are passing an actual parameter. Since I don't know much about spark and since the udf signature is a bit convoluted I'll try to explain what is going on with a simplified example. In practice udf is a function that given some explicit parameters and an implicit parameter list gives you another function; let's define the following function that given a pivot of type T for which we have an implicit Ordering will give as a function that allows us to split a sequence in two, one containing elements smaller than pivot and the other containing elements that are bigger: def buildFn[T](pivot: T)(implicit ev: Ordering[T]): Seq[T] => (Seq[T], Seq[T]) = ??? Let's leave out the implementation as it's not important. Now, if I do the following: val elements: Seq[Int] = ??? val (small, big) = buildFn(10)(elements) I will make the same kind of mistake that you are showing in your code, i.e. the compiler will think that I am explicitly passing elements as the implicit parameter list and this won't compile. The error message of my example will be somewhat different from the one you have because in my case the number of parameters I am mistakenly passing for the implicit parameter list matches the expected one and then the error will be about types not lining up. Instead, if I write it as: val elements: Seq[Int] = ??? val fn = buildFn(10) val (small, big) = fn(elements) In this case the compiler will correctly pass the implicit parameters to the function. I don't know of any way to circumvent this problem, unless you want to pass the actual implicit parameters explicitly but I find it quite ugly and not always practical; for reference this is what I mean: val elements: Seq[Int] = ??? val (small, big) = buildFn(10)(implicitly[Ordering[Int]])(elements)
Llívia Llívia (; ) is a town in the comarca of Cerdanya, province of Girona, Catalonia, Spain. It is a Spanish exclave surrounded by the French département of Pyrénées-Orientales. In 2009, the municipality of Llívia had a total population of 1,589. It is separated from the rest of Spain by a corridor about wide, which includes the French communes of Ur and Bourg-Madame. History Llívia was the site of an Iberian oppidum which commanded the region and was named Julia Lybica by the Romans. It was the ancient capital of Cerdanya in antiquity, before being replaced by Hix (commune of Bourg-Madame, France) in the Middle Ages. During the Visigothic period, its citadel, the castrum Libiae, was held by the rebel Paul of Narbonne against King Wamba in 672. As the "town (or 'city') of Cerdanya," 8th century Llívia may also have been the scene of the siege by which governor Abdul Rahman Al Ghafiqi of Muslim Spain rid himself of the Moorish (Berber) rebel Uthman ibn Naissa ("Munnuza"), who had allied himself with Duke Eudo of Aquitaine to improve the chances of his rebellion, ahead of the Battle of Tours (732 or 733), also known as the Battle of Poitiers. In 1659, the Treaty of the Pyrenees ceded the comarques of Roussillon, Conflent, Capcir, Vallespir, and northern Cerdanya ("Cerdagne") to the French Crown. Llívia did not become part of the Kingdom of France as the treaty stipulated that only villages were to be ceded to France, and Llívia was considered a town (vila in Catalan) and not a village because of its status as the ancient capital of Cerdanya. In 1939, at the end of the Spanish Civil War, the government of France was in a position—due to the enclave being completely surrounded by French territory—to deny access to it to the victorious forces of Franco and let Llívia remain a free territory of the defeated Republican government. However, this was never carried out. In any case, such an arrangement would not have survived the German occupation of France. During the era of Generalísimo Francisco Franco, residents required special passes to cross France to the rest of Spain. Today, with these countries in the Schengen Area, there are no frontier formalities and the only nuisance are cross-border infrastructure issues. Both countries share a hospital there, as well as other local initiatives. During the 2017 Catalan declaration of independence, some of the town residents voted for independence in a referendum deemed illegal by the Spanish government. Spanish police did not intervene in the village, presumably due to its location. Museum The Esteve Pharmacy, which is now located in Llívia's recently revamped municipal museum, is a complete 18th-century pharmacy donated to the town by the family who owned it, on condition the contents remain in the town. There are records of pharmacists practising in Llívia since medieval times. The pharmacy has a large display of albarelli, a type of ceramic jar used in pharmacies, as well as antique drugs, and one of the most important collections of prescription books in Europe. Education Escola Jaume I is located in Llívia. It was built in the 1950s. a new school will be constructed with a ground floor and a second floor. References External links Official site Government data pages Category:Municipalities in Cerdanya (comarca) Category:Municipalities in the Province of Girona Category:France–Spain border Category:Enclaves and exclaves Category:Populated places in the Province of Girona
Periodic solutions and chaos in the Barkley pipe model on a finite domain. Barkley's bipartite pipe model is a continuous two-state reaction-diffusion system that models the transition to turbulence in pipes, and reproduces many qualitative features of puffs and slugs, localized turbulent structures seen during the transition. Extensions to the continuous model, including the incorporation of time delays and constraining the system to finite open domains-a trigger for convective instability-reveal additional solutions to the system, including periodic solutions and chaos unseen in the original 1+1-dimensional system. It is found that the nature of solutions depends strongly on the size of the domain under study as well as choice of boundary conditions: on a finite domain for a particular window of parameter space, period doubling and chaos are observed.
Never Give Up, Never Surrender. Anothermia Dave Pallas (5 Minutes of Mystery) returns for Minute 51, as we hit the halfway point of the movie! Come along as we look at alien diets, sci-fi binoculars, and the life expectancy of space miners! Plus, Alex hits a new low for bad jokes! Follow us on Twitter @galaxyquestmin, and join us on Facebook at the Galaxy Quest Minute ListenerCon! Download here.
Both the Macomb Daily's Bruce MacLeod and the Detroit News's Ted Kulfan are reporting that the Nashville Predators will probably dress David Legwand tonight for Game 4 against the Detroit Red Wings: April 16, RedWingsCorner: The Predators are on the ice at Sommet Center. Well just about all of the Preds are. Center David Legwand is not practicing, following the save-it-for-the-game strategy that the team is using with his broken foot. Legwand didn't practice earlier this week, but did play more than 16 minutes in Monday's Game 3. So expect him to play again tonight unless there's an announcement otherwise. Jason Arnott is on the ice. After being dazed in a celebration scrum after scoring the winning goal, Monday, Arnott said that he will be ready for tonight's game. Post-practice update: Legwand on not practicing: "Just keeping it calmed down as much as possible. We'll see what goes on tonight in warmups, see how it feels and go from there." Legwand on the chance that he'll play tonight: "Probably, most likely be in. We obviously need a win tonight." April 16, Detroit News: The Predators just finished their morning skate and interview sessions with the media. Coach Barry Trotz stopped short of confirming Grosse Pointe native David Legwand will play again despite a bruised left foot. Legwand made his first appearance in the series Monday in Game 3, scored a goal, and was one of the Predators most effective players. Both MacLeod and MLive.com's own Ansar Khan confirm that Brett Lebda will play tonight, and Darren Helm may play as well: "It's been a tough couple of games here just watching," said Lebda. "All you can do is just be a cheerleader for the guys. It's hard. But it's a role that I had to accept. I'm going to get my chance tonight to play." Lebda said that last year's playoff run had him eager for more this spring: "I got a taste of a long run last year. I was anxious to get back in there and get another taste of it. When I sit and look back, that was what was the most disappointing thing. But those first two games, we played really well and got the wins. We should have had the win last game." Cheers to Lebda for keeping a positive attitude. Here's the line combinations that the Red Wings are using at practice this morning ... I certainly hope that the "Normal Unit" of Datsyuk, Zetterberg, and Holmstrom play together tonight... The fact that Pavel Datsyuk and Henrik Zetterberg are together in the morning skate means that they'll play on the same line for considerably longer than the two seconds they did at the start of Game 3. But splitting Datsyuk and Zetterberg onto separate lines could happen at any point in tonight's game. Babcock explained his logic behind putting Lebda back into the lineup to Kulfan: April 16, Detroit News: Brett Lebda will replace Andreas Lilja in the Red Wings line up Thursday in Game 4. Lebda's puck-moving ability and quickness was an ingredient the Wings were lacking in Game 3. "We thought last game we weren't as quick," Babcock said. "Lebs can push the puck up the ice. Our penalty kill has been good and Lils can block shots as good as anybody. You sacrifice something to get something." There could be one other change. Babcock indicated one forward was potentially going to sit out depending on how the player felt after warm ups. If someone had to sit out, Babcock said Darren Helm would go in the line up. Here's St. James' report on Helm's possible insertion into the lineup: April 16, Detroit Free Press: Babcock also said Darren Helm might be in depending on the health of the forwards. Based on the morning skate it didn't appear anyone was seriously banged up, but guys like Tomas Holmstrom, Mikael Samuelsson and Kris Draper are all coming off recent injuries. "There are lots of nerves going through me right now," Helm said after Detroit's morning skate at Sommet Center. "If I do get the chance, I definitely have to be as ready as I can to take this opportunity and really prepare. I'm just really excited and hopefully I get the chance. "I'm going to take warm-ups and after that, I'll find out. Nobody's really hurt or injured too bad, so having to take warm-ups definitely caught me a little off-guard." St. James says that Lilja's being benched because of a big "brain [flatulence]" that led to a Predators goal in Game 3: Lilja being scratched isn't much of a surprise, because he was the one who got caught in Game 3 making a bad change, leading to the Jason Arnott goal. Arnott scored when he took advantage of a bad change by the Wings; Nicklas Lidstrom had come on for Chris Chelios, but Lilja didn't do as good a job coming off so that Brian Rafalski could get on (the Wings want to have Lidstrom and Rafalski out against Arnott's line when at all possible). While Lilja is a bigger body and a good shot-blocker, Lebda has far more of an offensive upside, and adds speed to boot.
UNPUBLISHED UNITED STATES COURT OF APPEALS FOR THE FOURTH CIRCUIT UNITED STATES OF AMERICA, Plaintiff-Appellee, v. No. 97-4257 STEPHEN MULLINS, Defendant-Appellant. Appeal from the United States District Court for the Southern District of West Virginia, at Charleston. Charles H. Haden II, Chief District Judge. (CR-96-122) Submitted: May 29, 1998 Decided: September 10, 1998 Before ERVIN, LUTTIG, and MOTZ, Circuit Judges. _________________________________________________________________ Affirmed by unpublished per curiam opinion. _________________________________________________________________ COUNSEL Jane Charnock, CHARNOCK & CHARNOCK, Charleston, West Virginia, for Appellant. Rebecca A. Betts, United States Attorney, Susan M. Arnold, Assistant United States Attorney, Charleston, West Virginia, for Appellee. _________________________________________________________________ Unpublished opinions are not binding precedent in this circuit. See Local Rule 36(c). OPINION PER CURIAM: Stephen Mullins appeals his conviction and sentence after a guilty plea to conspiracy to distribute and possess with intent to distribute methamphetamine in violation of 21 U.S.C. § 846 (1994). Mullins' attorney has filed a brief in accordance with Anders v. California, 386 U.S. 738 (1967), raising two issues but stating that, in her view, there are no meritorious grounds for appeal. Mullins has filed a supplemen- tal brief pro se, raising four additional issues. After a thorough review of the record, we affirm. Mullins' counsel first contends that the district court erred in deny- ing Mullins' pro se motion to withdraw the guilty plea because coun- sel was ineffective for failing to make the motion. For ineffective assistance of counsel to constitute a fair and just reason to withdraw a guilty plea, it must be of constitutional magnitude. See United States v. Lambey, 974 F.2d 1389, 1394 (4th Cir. 1992) (en banc). Mullins cannot show that counsel's failure to timely file the motion on his behalf prejudiced him. See United States v. Craig, 985 F.2d 175, 179 (4th Cir. 1993) (providing standard). Even if the motion had been timely filed, he did not establish, inter alia , that his plea was not knowing and voluntary. See United States v. Moore, 931 F.2d 245, 248 (4th Cir. 1991) (outlining factors courts consider in ruling on motion to withdraw). Mullins also claims that the district court erred in denying his motion to withdraw his guilty plea because he "just didn't under- stand" that he could be sentenced as a career offender. Although Fed. R. Crim. P. 11 does not require the district court to inform Mullins of this possibility, the court did so. The court also informed Mullins of the statutory minimum and maximum sentences (the guideline range based on his classification as a career offender fell within that range), that the guideline range could not be determined until a pre- sentence report was prepared, and otherwise fully complied with Rule 11. See United States v. Wilson, 81 F.3d 1300, 1307 (4th Cir. 1996) ("The key to a [Rule] 32(e) motion is whether or not the Rule 11 pro- ceeding was properly conducted."). On these facts, we find no abuse 2 of discretion in the district court's denial of the motion to withdraw. See id. at 1305. Mullins' counsel also disputes that Mullins was a career offender. We review this issue de novo. See United States v. Dickerson, 77 F.3d 774, 775 (4th Cir.), cert. denied, #6D6D 6D# U.S. ___, 65 U.S.L.W. 3259 (U.S. Oct. 7, 1996) (No. 95-9207). Mullins was in his thirties when he committed the offense, he pled guilty to conspiracy to distribute methamphetamine (a controlled substance offense), and he had two prior felony convictions for armed robbery and aggravated assault (crimes of violence). See U.S. SENTENCING GUIDELINES MANUAL §§ 4B1.1, 4B1.2, comment. (n.2) (1994). We also note that Mullins' 1978 armed robbery conviction qualified as a prior felony because Mullins served a portion of the ten-year sentence during the fifteen- year period predating the commencement of the instant offense. See USSG § 4A1.2(e)(1); USSG § 4B1.2, comment. (n.4) (stating that § 4A1.2(e)(1) applies to the counting of convictions under § 4B1.1); United States v. Powell, 922 F.2d 212, 213-14 (4th Cir. 1991). There- fore, the district court did not err in classifying Mullins as a career offender. See Dickerson, 77 F.3d at 775. Mullins raises four claims in his supplemental pro se brief, none of which merit extended discussion. First, Mullins' claims that his guilty plea was not knowing and voluntary because he was threatened with false information provided by his counsel and he was misled by the plea agreement's failure to contain the word "conspiracy." This claim is meritless. At the Fed. R. Crim. P. 11 hearing, Mullins stated that he had not been threatened or coerced and that he understood he was pleading guilty to conspiracy to distribute methamphetamine. See United States v. DeFusco, 949 F.2d 114, 119 (4th Cir. 1991) (stating that defendant's statement at Rule 11 hearing that he was not coerced or threatened constitutes "strong evidence of the voluntariness of his plea"); Via v. Superintendent, Powhatan Correctional Ctr., 643 F.2d 167, 171 (4th Cir. 1981) (holding that statements made at plea hearing that facially demonstrate plea's validity are conclusive absent a com- pelling reason why they should not be, such as ineffective assistance of counsel). Next, although Mullins claims that the district court held him accountable for drugs that were not reasonably foreseeable to him, no plain error resulted given that Mullins was a career offender. See United States v. Perkins, 108 F.3d 512, 516 (4th Cir. 1997) (stat- 3 ing standard of review). Third, Mullins contends that he was not allowed to present mitigating evidence at sentencing, as required by Fed. R. Crim. P. 32(c)(3)(C). Because the record belies his claim, there was no plain error. See United States v. Cole, 27 F.3d 996, 998 (4th Cir. 1994) (applying plain error analysis to claim of denial of allocution). Finally, Mullins' numerous claims of ineffective assis- tance of counsel should be raised in a motion under 28 U.S.C.A. § 2255 (West 1994 & Supp. 1998), and not on direct appeal, because the record does not conclusively show that counsel was ineffective. See United States v. King, 119 F.3d 290, 295 (4th Cir. 1997). As required by Anders, we have examined the entire record and find no other meritorious issues for appeal. Because the record dis- closes no reversible error, we affirm Mullins' conviction and sen- tence. This court requires that counsel inform her client, in writing, of his right to petition the Supreme Court of the United States for fur- ther review. If the client requests that a petition be filed, but counsel believes that such a petition would be frivolous, then counsel may move in this court for leave to withdraw from representation. Coun- sel's motion must state that a copy thereof was served on the client. We dispense with oral argument because the facts and legal conten- tions are adequately presented in the materials before the court and argument would not aid the decisional process. AFFIRMED 4
Q: What is the origin of the phrase "extirpated as a potential munition" I recently came across this statement in the Perl documentation: extirpated as a potential munition derived from the sentence: "Creates a digest string exactly like the crypt(3) function in the C library (assuming that you actually have a version there that has not been extirpated as a potential munition)." Is this not a very odd phrase to use in regards to a function becoming defunct or does it have some special meaning involved within cryptography? A: Before the rise of personal computing, the most significant use of cryptography was to keep war plans secret. Keep in mind that programmable computing as we know it essentially began with Turing's work breaking German codes in World War II, and the age of personal computing was beginning just as the Cold War was drawing to a close--not that anyone knew it at the time! If you had an algorithm that could encrypt data such that the government couldn't read it, and it fell into the hands of the Russians, they could use this encryption to safely coordinate first-strike plans against the West, potentially setting up a nuclear attack. This was a very real fear back in the day, and even after the Soviet Union fell, neither the nuclear weapons nor America's enemies magically went away. Therefore, the government classified strong encryption technology as "munitions", and exporting it was regulated under the same rules as military-grade weaponry. This lasted up until the dawning of the World Wide Web and the rise of e-commerce, which required strong encryption to foil eavesdropping and fraud, and enough of the Internet made enough of a stink about it that the rules were changed, in the name of economic progress.
Tag Archives: Jorge Brooks The 1980’s was a special time in my life. It was another phase in my development in loving film. That decade saw many films starring kids and teens in coming-of-age tales both comedic, thrilling, dramatic and poignant. While there were many filmmakers who delved into this genre it was Steve Spielberg who mined it to great effect culminating in his classic boy-meets-alien film, E.T.: The Extra-Terrestrial. It’s been almost 30 years since the release of that film and now comes a filmmaker who seem to have grown up idolizing and loving Spielberg films of that era. The year is now 2011 and J.J. Abrams is that filmmaker who dared to pay homage to those very same coming-of-age Spielberg films of the 80’s with his very own simply titled Super 8. From the very moment the film begins there’s a sense of wonderment as we, the audience, meet young kids who become the central characters of Super 8. The film takes place in the early days of 1979 in the town of Lillian, Ohio as Joe Lamb (Joel Courtney) tries to cope with the death of his mother. His friends keep him busy and dwelling on this tragedy through the Super 8 film they’re making in their spare time after school. These early scenes we begin to see the dynamics of the group as Joe acts as the calming influence on the group’s filmmaker, Charles (Riley Griffiths), the neurotic actor in Martin (Gabriel Basso) and the group’s stuntman/special effects tech in Carey (Ryan Lee). They all meet up at an old train depot where they plan to shoot scenes for their Super 8 zombie film. Into this eclectic group of kids comes in Alice (Elle Fanning) to play the wife to Martin’s detective character in their film. It’s the scenes between the kids which lifts Super 8 from just being a nostalgic film to one that’s charming and magical. These scenes captures the creativity and youthful energy kids have always had no matter the era and place. These kids don’t act like stereotypes of what Hollywood thinks kids in films should act. There’s still little of the cynical teen dialogue that films nowadays give kids to say to make them seem more mature and worldly. There’s a sense of innocence in how these kids interact with each other. Some have called these scenes as being too on-the-nose nostalgic of Spielberg films of the 80’s. What some might call nostalgic I prefer to call as timeless. I still remember myself behaving with my childhood friends the way these kids did in this film If Super 8 had just been about these group of kids trying to finish their Super 8 zombie film I conjunction with the dysfunction in the two main leads in Joe and Alice’s home life then Abrams film would’ve been the instant classic some have dubbed it. There’s only one problem with this and that’s the last half hour of the film and the scenes leading up to that involving the train derailment and the arrival of the U.S. Air Force to clean things up. The film begins to take on a split personality as these new elements get introduce to what has been a great coming-of-age story. It’s these new elements and the final half hour which shows Abrams trying to combine a sweet story of kids and their lives growing up in small-town with an otherworldy and conspiracy tale that seem to come out of left field. By the time the final act of Super 8 arrives it becomes a different film altogether and the transition doesn’t work as well as the filmmakers might have hoped it would. Sure, this final reel has the thrills, explosions and danger, but the tonal shift in the story became so jarring that I had wished that Abrams just made two films instead of one. One film being the coming-of-age story and the other a thrilling sci-fi film. Despite this I still enjoyed the film and I definitely loved the first two-thirds. The performances by Joel Courtney and Elle Fanning as Joe and Alice became the focal point for the story’s emotional foundation. Elle Fanning’s performance as Alice was one of the best things about Super 8. She nails every scene where she has to show extreme ranges of emotions but at the same time not try to oversell them. There’s a scene in the middle of the film where she begins to recount a personal detail as Joe sits behind her listening. Emotions begin to overwhelm her, but as kids moving towards teenhood are wont to do she tries to hold back the tears just waiting to flow freely and the sobs wanting to escapes. I wouldn’t be surprised if this scene alone had more than a couple people in the audience remembering similar events in their lives and just sobbing along with Alice. Super 8 has been advertised as this mysterious film that may or may not have aliens but does pay homage to Spielberg and kid films of the 80’s. Abrams’ film definitely delivers on the thrills in the end, but it could’ve been so much more if it just stayed on course with just being about the kids and their magical time together making an amateur Super 8 zombie film in 1979. That would’ve been a film that deserved labels of instant classic. All in all, Super 8 comes across as one of the more entertaining and magical films of the summer of 2011 if not the entire year. Make sure to stick around as the end credits roll to see the fruits of the kids labor titled simply as “The Case”.
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INTRODUCTION {#SEC1} ============ It is becoming increasingly realized that within bioinformatically-defined classes of riboswitches there exists variation in both the cognate metabolite that regulates gene expression and the ability to discriminate between chemically related metabolites ([@B1]). Diversity in ligand recognition within a defined class is exemplified by the ykkC family of riboswitches. Originally identified as a sequence upstream of genes encoding multidrug resistance efflux pumps and other transporters ([@B2]), these riboswitches remained orphan until it was determined that some members respond to guanidine ([@B3]). Further examination of this class revealed multiple distinct classes sharing a secondary structure, but containing sequence variation within some of the most conserved regions. Distinct classes of the ykkC family of riboswitches have most recently been verified to bind the purine biosynthetic precursor phosphoribosyl pyrophosphate (PRPP) ([@B4]), the bacterial alarmone ppGpp ([@B5]), and nucleoside diphosphates ([@B6]). Other examples of ligand recognition diversity have been observed within class-II cobalamin riboswitches that bind adenosyl- and methylcobalamin with a spectrum of selectivities ([@B7]), a subset of GEMM-I riboswitches that bind cyclic AMP-GMP rather than cyclic di-GMP ([@B8]) and rare FMN riboswitches that bind an alternative but unknown compound ([@B9]). Despite the realization that effector ligand diversity might be a widespread phenomenon within bioinformatically-defined riboswitch classes, identifying functional variation is challenging. Based on current knowledge, most sequence variation within a class does not lead to a change in ligand selectivity ([@B1]). To identify functional variants, the Breaker laboratory recently developed a new computational approach to examine established riboswitch classes for detecting unrecognized ligand binding diversity. This was achieved by using crystal structures of riboswitch aptamer--ligand complexes to identify the first shell of ligand-interacting nucleotides and survey the Rfam sequence alignment of that class to identify members that vary from consensus at these positions. This approach resulted in identification of variant groups within the guanine, c-di-GMP, glycine and FMN classes ([@B1]). One of the variant classes of guanine riboswitches discovered was predicted and validated as a second class of 2′-deoxyguanosine (2′-dG) binders--referred to as the 2′-dG-II class (originally annotated as the 'UCC variant group') ([@B1]). These RNAs contain a first shell of ligand-interacting nucleotides whose identity is U22, C51, C74, similar to the equivalent nucleotides in the Mesoplasma florum (Mfl) I-A 2′-dG-I riboswitches (C31, C58, C80) (red nucleotides, Figure [1](#F1){ref-type="fig"}) ([@B10]). The identity of the pyrimidine at position 51/58, which directly interacts with the N3/N9 face (sugar edge) of the purine ligand, is critical for establishing selectivity for nucleobase versus nucleoside binding across the purine riboswitch family ([@B11],[@B12]) (Figure [2A](#F2){ref-type="fig"}, [B](#F2){ref-type="fig"}). However, there are further differences between the two classes of 2′-dG binders around the ligand binding pocket that distinguish them. First, the 2′-dG-II riboswitches have an insertion element within J3/1 that is unique amongst the purine riboswitches ([@B1]). A second notable change is that the junction-proximal base pair in P1 is a G--C pair whereas in all other purine riboswitch classes it is a nearly invariant A--U pair ([@B1]). These, along with other differences further away from the ligand binding pocket such as in L2 and L3, may be important for the ability of this new class of riboswitches to bind 2′-dG with high affinity and selectivity. ![Secondary structure of representatives of the three classes of riboswitches within the purine family. Sequences are based upon those used for determination of the crystal structure of (A) the B. subtilis xpt guanine riboswitch aptamer domain (PDB ID: 4FE5), (B) the M. florum I-A class-I 2′-dG riboswitch aptamer domain (PDB ID: 3SKI), and (C) the env1 class-II 2′-dG riboswitch (this study). The secondary structural elements which are common to all three classes, are labeled as P (paired), J (joining) and L (loop). Nucleotides highlighted in red directly interact with the ligand nucleobase and nucleotides in blue within the env1 sequence represent key differences in the ligand binding three-way junction between the xpt and env1 RNAs. The dashed lines represent two sets of base-base interactions in the junction that distinguish the three classes of riboswitches.](gkz839fig1){#F1} ![Overall structure of the env1 2′-dG-II riboswitch. (A) Secondary structure of the environmental sequence 1 (env1) 2′-dG-II riboswitch annotated with nucleobase-nucleobase interactions. Base interaction notation is that of Leontis and Westhof ([@B57]). (B) Cartoon representation of the crystal structure of the env1 riboswitch aptamer domain in complex with 2′-deoxyguanosine (magenta). Watson--Crick helices (P1 -- P3) are denoted in blue, the two terminal loops (L2 and L3) in orange and the three joining regions of the three-way junction (J1/2, J2/3 and J3/1) are shown in cyan, green and yellow, consistent with panel (A). (C) Superimposition of the B. subtilis xpt guanine riboswitch aptamer domain (orange) with env1 2′-dG riboswitch aptamer domain (blue). In each RNA, the P1 helix was truncated to the three Watson--Crick base pairs proximal to the three way junction. The RNAs align with an r.m.s. deviation of 1.95 Å using PyMOL.](gkz839fig2){#F2} In this work, we present a structural and biochemical analysis of the 2′-dG-II class of riboswitches that explains its selectivity for 2′-dG over other purine nucleobases and nucleosides. While the global architecture of the 2′-dG-II riboswitch aptamer domain is highly similar to the other classes within the purine riboswitch family, there are significant differences around the ligand binding pocket between the two 2′-dG classes. Notably, the two-nucleotide insertion element in J3/1 enables base-base interactions not observed in the other purine classes. Analysis of a series of mutants indicates that while the J3/1 insertion element and the identity of the junction-proximal base pair in P1 play a central role in promoting 2′-dG affinity, other nucleotides within the junction also contribute towards achieving high affinity binding. Binding analysis of a subset of aptamers from the 2′-dG-II family revealed a spectrum of selectivities for 2′-dG versus 2′-rG, suggesting that some members may respond to both nucleosides, further highlighting potential hidden variation within bioinformatically-defined riboswitch classes. MATERIALS AND METHODS {#SEC2} ===================== RNA preparation {#SEC2-1} --------------- The env1 2′-dG aptamer domain RNA and derivatives were in vitro transcribed by T7 RNA polymerase from a PCR-generated DNA template using previously described methods ([@B13]). Sequences of all RNAs used in this study are given in [Supplementary Table S1](#sup1){ref-type="supplementary-material"}. After incubating for 3 h at 37°C, the transcription reaction was buffer exchanged into Milli-Q water and purified using denaturing polyacrylamide gel electrophoresis. Product was extracted using the crush and soak technique at 4°C into 0.5× TBE buffer (45 mM Tris-borate, 1 mM EDTA, pH 8.0) followed by buffer exchange with 0.5× TE buffer (5 mM Tris, 0.5 mM EDTA, pH 8.0) and concentrated to a volume of 500 μl using a 10 kDa Amicon centrifugal microconcentrator. RNA concentrations were determined using a calculated molar extinction coefficient at 260 nm wavelength; RNA was stored at --20°C until use. For crystallization and ITC, RNA was refolded by heat/cooling at 95°C for 3 min and incubating on ice for 5 min in TE buffer. Native gel electrophoresis was used to assess whether the refolded RNA adopted a single, monomeric conformation ([@B14]). RNA crystallization {#SEC2-2} ------------------- The env1 2′-dG aptamer domain RNA was crystallized at 30°C using the hanging drop diffusion method. 4 μl drops composed of a 1:1 ratio of RNA-ligand mixture to precipitant mixture were suspended above 500 μl of 35% 2-methyl-2,4-pentanediol (MPD). The RNA-ligand mixture contained 300 μM RNA and 600 μM 2′-deoxyguanosine while the precipitant mixture contained 40 mM sodium cacodylate pH 6.0, 23% v/v MPD, 18 mM cobalt hexammine, 80 mM potassium chloride, and 12 mM sodium chloride. Hanging drops were incubated for 2--3 days to allow crystals to reach maximum size. To cryoprotect, crystals were soaked in a precipitant mixture containing 35% MPD for 5 min, and flash frozen in liquid nitrogen. Data were collected on a home-source Rigaku MicroMax-007 HF X-ray source with a Dectris Pilatus 3R 200K-A detector and processed with HKL3000. Screening for crystals that diffract X-rays to high resolution and data collection methods were using standard practice for X-ray crystallography ([@B15],[@B16]). Crystallographic data collection statistics are given in [Supplementary Table S2](#sup1){ref-type="supplementary-material"}. Structure determination, refinement and analysis {#SEC2-3} ------------------------------------------------ An electron density map was calculated by molecular replacement using Phaser ([@B17]) in PHENIX ([@B18]) using the three helices of the B. subtilis xpt guanine riboswitch (GR) RNA (P1 nucleotides (nt) 15--21 and 75--81, P2 nt 25--31 and 39--45, P3 nt 54--59 and 67--72) as a starting model (PDB ID: 4FE5), excluding all non-helical linker regions (J1/2, L2, J2/3, L3, J3/1). Model refinement was initiated by replacing the sequence of the GR helices with that of env1 using Coot ([@B19]), followed by refinement in PHENIX. Further rounds of iterative model building and refinement were performed in which the rest of the RNA model was built, the ligand placed within the binding pocket and finally solvent molecules were placed. Standard approaches to reduce model bias in molecular replacement were employed throughout electron density map calculation and model building ([@B20],[@B21]). The final model statistics are provided in [Supplementary Table S2](#sup1){ref-type="supplementary-material"}. Isothermal titration calorimetry (ITC) {#SEC2-4} -------------------------------------- RNA-ligand binding affinities were quantified by ITC using methods described previously ([@B22]). RNA was dialyzed overnight in ITC buffer containing 50 mM K-HEPES pH 7.5, 20 mM MgCl~2~, and 100 mM KCl at 4°C, similar to previously published conditions ([@B10]). Ligand was dissolved in ITC buffer at 65°C and centrifuged to remove undissolved particles. Experiments were performed in triplicate using a Microcal ITC-200 calorimeter. Titrations were performed at 30°C with a reference power of 9 μcal/s. RNA was loaded into the sample cell at concentrations of 5--50 μM, after which ligand was titrated into the cell using the syringe in 19, 2.0 μl injections at concentrations between 50--500 μM. c values were between 0.5 and 1120, with all but the weakest binders \>1 and all but the tightest binder below 500. Data were fitted to a single-site binding model with Origin 7.0 ITC software (Microcal Software) to determine the apparent dissociation constant, K~D,app~; representative data and fits are shown in [Supplementary Figure S1](#sup1){ref-type="supplementary-material"}. Data and statistical analysis was performed in accordance to best practice as described ([@B23],[@B24]). RESULTS {#SEC3} ======= Design and crystallization of 2′-dG-II aptamer domains {#SEC3-1} ------------------------------------------------------ To validate their identities as 2′-dG riboswitches, we first verified the 2′-deoxyguanosine binding ability of several 2′-dG-II class RNAs using isothermal titration calorimetry (ITC). The env23 sequence (RNA nomenclature adopted from Weinberg et al. ([@B1])) used to determine the ligand binding specificity of this class was observed to bind 2′-dG with a K~D,app~ of 290 ± 50 nM (Table [1](#tbl1){ref-type="table"}), consistent with in-line probing values ([@B1]). In addition, we investigated a sequence (env1) from the sequence alignment of this class of riboswitches that most closely resembled the B. subtilis xpt guanine riboswitch, particularly with respect to the terminal loop-loop (L2--L3) interaction ([@B25]). Prior structural studies using the xpt guanine aptamer to host alternative ligand binding pockets in the three-way junction revealed that these RNAs, like the parental sequence, were readily crystallizable ([@B11],[@B26]). 2′-dG binding by env1 was determined by ITC to be 34 ± 1 nM (Table [1](#tbl1){ref-type="table"}), less than an order of magnitude weaker than the ∼4 nM binding affinity of xpt guanine riboswitch for guanine ([@B29]). ###### ITC analysis of 2′-dG and rG binding to purine family riboswitches Riboswitch Class K ~D,2′-dG~ (nM) K ~D,rG~ (nM) K ~rel~ (rG/2′-dG) ----------------------- ----------- -------------------- ----------------- ---------------------- *env1* 2′-dG-II 34 ± 1 89 ± 10 2.6 *B. subtilis xpt* G/A 7700 ± 100 36 000 ± 1000 2.6 *env30* 2′-dG-II 2400 ± 900 36 000 ± 1000 15 **M. florum I-A 2′-dG-I 190 ± 10 5000 ± 600^a^ 27 xpt GdG 5B ^a^ synthetic 350 ± 100 10 000 ± 100 29 env6 2′-dG-II 88 ± 3 3000 ± 200 35 env23** 2′-dG-II 290 ± 50 51 000 ± 4000 180 ^a^Data from reference ([@B11]). The env23 and env1 RNAs in complex with 2′-dG were screened for diffraction quality crystals using a strategy similar to that of the xpt aptamer-hypoxanthine complex ([@B30]). For each, a series of RNAs was created whose P1 helix lengths varied between 5 and 8 bp, with all variants having a single 3′-adenosine overhang. Initial screening yielded crystals of the env1 RNA, but were found to be irreproducible. Analysis of the length of RNA in the crystals and that remaining in solution using denaturing acrylamide gel electrophoresis revealed that RNA in crystals were slightly longer than the non-crystallizing RNA remaining in the mother liquor, suggesting a nontemplated 3′-nucleotide was added by T7 RNA polymerase ([@B31],[@B32]). We subsequently screened an additional set of single nucleotide additions to the 3′-end of env1 using transcription templates that have two 2′-O-methoxy groups at the 3′-end to prevent nontemplated nucleotide addition ([@B33],[@B34]) and found that a guanosine added to the 3′-end resulted in reproducible crystals, while addition of an adenosine or uridine did not. Subsequent analysis of the lattice contacts in the env1 crystal structure revealed that the Watson--Crick face of the 3′ guanosine forms hydrogen bonding interactions with the β-phosphate of the 5′-residue of a neighboring molecule. It should be noted that a similar strategy was used to obtain reproducible crystals of the SAM-I/IV riboswitch aptamer domain ([@B35]). Crystals of the aptamer domain of the env1 2′-dG-II class riboswitch in complex with 2′-deoxyguanosine were obtained in the P4~1~22 space group and diffracted using a home source rotating copper anode x-rays to 2.8 Å resolution (crystallographic data and model refinement statistics provided in [Supplementary Table S2](#sup1){ref-type="supplementary-material"}). The structure was determined by molecular replacement ([@B17]) using the three helices of the xpt guanine riboswitch RNA as an initial search model (PDB ID: 4FE5, ([@B36])), as described in the methods. The initial electron density map ([Supplementary Figure S2](#sup1){ref-type="supplementary-material"}) was sufficiently clear to build the remaining RNA and the model was further built and refined using PHENIX ([@B18]). The final model had R~work~ = 24.4% and R~free~ = 27.6% values with overall good geometry as determined using MolProbity ([@B37],[@B38]). Global structure of the env1 2′-dG-II aptamer domain {#SEC3-2} ------------------------------------------------------ The secondary structure and global architecture of the env1 2′-dG-II riboswitch aptamer domain (Figure [2A](#F2){ref-type="fig"}, [B](#F2){ref-type="fig"}) adopts the same three-way junction supported by a distal tertiary interaction observed in all structures of purine family riboswitches ([@B12],[@B39]). Superimposition of the B. subtilis xpt guanine and env1 2′-dG-II aptamers reveals that the three helices are organized around the central three-way junction in an identical fashion (Figure [2C](#F2){ref-type="fig"}). The main architectural difference between the two RNAs is the presence of an additional base pair in the env1 P3 helix (seven versus six base pairs in xpt)---similar to the M. florum 2′-dG-I aptamer. To preserve critical tertiary loop contacts between L2 and L3, this additional base pair shifts the P3 helix further into the binding core relative to xpt in both the 2′-dG-I ([@B12]) and 2′-dG-II RNAs. However, it should be noted that a seven base pair P3 helix is common within the guanine class of purine family riboswitches as well ([@B36]), so this feature is not unique to 2′-deoxyguanosine binding. The L2--L3 interaction of 2′-dG-II is nearly identical to the tertiary interactions observed in the B. subtilis xpt guanine ([@B39],[@B41]), B. subtilis pbuE adenine ([@B40]), and V. vulnificus add adenine ([@B41]) riboswitches (Figure [3](#F3){ref-type="fig"}). However, env1 exhibits three differences from xpt in the tertiary loop region: (i) an adenosine versus guanosine at the first position of L2, (ii) an A•A mismatch as the closing pair at the top of the P3 helix in env1, which is an A--U base pair in xpt, and (iii) a different Watson--Crick pair closing P2. To determine if these differences impact ligand recognition, we substituted the L2-L3 loop-loop region of env1 and tested affinity for 2′-dG. Substitution of the entire env1 L2-L3 loop and proximal two base pairs of P2 and P3 with the corresponding xpt sequence had no effect on 2′-dG binding (K~D~ = 30 ± 2 nM, Table [2](#tbl2){ref-type="table"}), indicating that the env1 tertiary loop region is interchangeable with that of xpt and likely plays no role in determining ligand selectivity in the guanine and 2′-dG-II classes of purine riboswitches. Conversely, because of significant differences between L2 of M. florum and env1 beyond the central two Watson--Crick G--C base pairs (Figure [3A](#F3){ref-type="fig"}, [B](#F3){ref-type="fig"}), the two RNAs superimpose poorly in this region (Figure [3D](#F3){ref-type="fig"}). ![L2-L3 interactions in the purine riboswitch family. (A) Map of long-range interactions between L2 and L3 in the env1 2′-dG-II riboswitch aptamer domain. Notation is that of Leontis and Westhof ([@B57]). (B) Stereoscopic image of long-range interactions between L2 and L3 in the M. florum I-A 2′-dG-I riboswitch aptamer domain. Dashed lines represent single hydrogen bonding interactions. (C) Wall-eyed stereo view of the alignment of the L2-L3 interaction of the xpt aptamer domain (orange) and env1 aptamer domain (blue). R.m.s. deviation between the substructures is 0.50 Å. (D) Wall-eyed stereo view of the alignment of the L2--L3 interaction of the M. florum I-A riboswitch aptamer domain (green) and env1 aptamer domain (blue).](gkz839fig3){#F3} ###### ITC analysis of 2′-dG binding to 2′-dG-II riboswitch mutants RNA K ~D,dG~ (nM) K ~rel~ (K~D,mut~/K~D,wt~) ----------------------------- ----------------- ---------------------------------- **env1 (wild type) 34 ± 1 1 env1 with xpt L2-L3 30 ± 2 0.88 env1 U75A 1600 ± 300 46 env1 C76G 100 ± 40 2.9 env1 Δ(U75,C76) 240 ± 50 7.1 env1 A77U 250 ± 10 7.4 env1 C78A 41 000 ± 9000 1200 env1 C51U 620 ± 180 18 env1 G21A,C79U 570 ± 30 17 env1 C47,48U 110 ± 10 3.2 env1 C48A** 7.1 ± 1.4 0.21 Local architecture of the three-way junction {#SEC3-3} -------------------------------------------- Within the three-way junction of the 2′-dG-II aptamer domain is a set of nucleobase-mediated interactions that are universally conserved within the purine riboswitch family (grey box, Figure [4](#F4){ref-type="fig"}). These interactions are primarily mediated by highly conserved nucleotides and/or nucleobase interactions in the joining strands (J1/2, J2/3 and J3/1) of the three-way junction along with the two junction-proximal base pairs of the P1 helix. Most distal to the P1 helix is a universally conserved base triple formed by a Watson--Crick pair between the first and last nucleotides of J2/3 (G46--C53) and a Watson--Crick/sugar edge interaction between A23 of J1/2 and G46. Adjacent to this triple is a Watson--Crick pair between A52 and U22. While in the guanine/adenine and 2′-dG-II classes this is a U--A pair, it is a C--G pair in 2′-dG-I ([@B12]); mutation of the U--A pair in the B. subtilis xpt guanine riboswitch from to a C--G pair imparts only a modest loss in binding affinity ([@B42]) in support of the general requirement for a Y22--R52 base pair. The third layer in the junction is a base triple involving C51, C78 and 2′-dG. This triple is universal within the purine family, although the mode of base-base interactions differs amongst the classes (vide infra). C50 of J2/3 engages the junction-proximal Watson--Crick pair (G21--C79) of the P1 helix through a two hydrogen bonding interaction that is conserved throughout the purine family, despite the differing G--C nucleotide identity of the junction-proximal base pair of P1 in 2′-dG-II compared to the A--U pair found in the other classes. The one variable structural aspect of the core is how the second junction proximal base pair in P1 (U20--A80) interacts with J2/3. Disruption of this interaction in the B. subtilis xpt guanine riboswitch has a very modest negative affect on ligand binding affinity ([@B42]). ![Architecture of the three-way junction. (A) Schematic of the base interactions between the three strands of the junction (coloring consistent with Figure [2](#F2){ref-type="fig"}) and the P1 helix. Grey shading represents base-base interactions universal to the purine riboswitch family. Red interactions denote those unique to the 2′-dG-II aptamer domain. Notation is that of Leontis and Westhof ([@B57]). (B) Wall-eyed stereo view of the architecture of the three-way junction. (C) Wall-eyed stereo view of the three-way junction rotated 90° clockwise relative to the perspective in panel B.](gkz839fig4){#F4} A two-nucleotide insertion in J3/1 is unique to 2′-dG-II purine riboswitches {#SEC3-4} ---------------------------------------------------------------------------- The most significant difference between the 2′-dG-II and other purine riboswitches within the three-way junction is a two nucleotide insertion in J3/1 that is absent in both the guanine/adenine and 2′-dG-I classes of purine riboswitches (Figure [5A](#F5){ref-type="fig"}, [B](#F5){ref-type="fig"}). This insertion is present in all members of the 2′-dG-II class, with the first position being an invariant uridine nucleotide while the second nucleotide is variable. In the crystal structure of env1(2′-dG-II), this insertion element promotes new base-base interactions within the three-way junction. U75 forms a base pair with the Hoogsteen face of A24 (Figure [5C](#F5){ref-type="fig"}). In the xpt guanine riboswitch this nucleotide is unpaired and stacks with the bottom of the P3 helix while the equivalent nucleotide in Mfl-IA(2′-dG-I) forms a base triple with the junction-proximal base pair in P2. The second nucleotide of the insertion, C76, is flipped away from the junction such that it does not make contacts with other bases in the RNA. Supporting this observation, mutation of C76 to a guanosine has minimal effect on 2′-dG binding affinity, reducing it only 2.9-fold (Table [2](#tbl2){ref-type="table"}). ![Interactions mediated by the U75-C76 J3/1 insertion element. (A) Local structure of the J3/1 element (nucleotides U75--C78) in the env1 2′-dG-II riboswitch aptamer domain and its interaction with ligand. Base-base interactions are denoted by grey dashed lines. (B) Local structure of J3/1 (nucleotides A73--C74) and its interactions with ligand (hypoxanthine, HX) in the xpt guanine riboswitch aptamer domain. (C) Base pairing interaction between U75 of the J3/1 insertion element and A24. (D) Indirect water-mediated interaction between A73 and the U22--A52 base pair in the xpt riboswitch (4FE5). Note that these highly ordered waters are consistently observed across multiple high-resolution crystal structures of the xpt riboswitch. (E) Direct interaction between A77 and the U22--A52 base pair in the junction.](gkz839fig5){#F5} To further understand the role of the J3/1 insertion element in ligand recognition, we examined it in the context of both env1(2′-dG-II) and xpt. Strikingly, deletion of these two nucleotides in env1 only results in a moderate loss of affinity for 2′-dG (7.1-fold, Table [2](#tbl2){ref-type="table"}), while a U75A mutant reduces affinity 46-fold. A simple explanation for this observation is that a more sterically bulky purine at position 75 that still engages with A24 would push the backbone of J3/1 outwards, potentially disrupting a number of neighboring interactions as opposed to the deletion mutant that only ablates the A24--U75 pair. The deletion mutant is more modest than the C51U mutation that results in an 18-fold loss of 2′-dG binding affinity. These data indicate that the two nucleotide insertion element in J3/1 is not essential for promoting 2′-dG binding in this class of riboswitches, although the A24-U75 interaction increases affinity. Insertion of these two nucleotides into the xpt guanine riboswitch aptamer at the equivalent position does not promote 2′-dG binding, as affinity does not change compared to wild type xpt (8.1 ± 0.6 μM and 7.7 ± 0.4 μM, respectively). However, its affinity for hypoxanthine (HX)---one of its cognate ligands---is weakened from 0.73 ± 0.1 μM ([@B39]) to 21 ± 2 μM, a 29-fold reduction in affinity. Thus, the J3/1 insertion in the context of the xpt guanine riboswitch changed selectivity from favoring HX by ∼10-fold to favoring 2′-dG by 2.6-fold. Further alteration of xpt by including the U51C mutation that was previously shown to promote 2′-dG binding (xpt(U51C), K~D,app~ = 12 ± 1 μM, ([@B11])) increased the affinity 4.2-fold to 1.6 ± 0.1 μM while nearly abolishing affinity for hypoxanthine (\>100 μM). Thus, the identity of position 51 in concert with the two nucleotide insertion in J1/3 promotes both tighter and more selective 2′-dG binding in the context of the xpt aptamer. These data suggest that these nucleotides are the strongest drivers of nucleoside versus nucleobase binding selectivity in purine riboswitches, but other changes to the sequence in the junction are required to achieve the highest affinity for 2′-dG. The second direct base-base interaction promoted by the insertion element is via adenosine 77. In other purine riboswitch family members, this nucleotide is coplanar with a Y22-R52 Watson--Crick pair above the ligand-binding triple in the three-way junction. In xpt, the U22--A52 base pair forms a water-mediated interaction with A73 (Figure [5D](#F5){ref-type="fig"}), while in Mfl-IA the equivalent nucleotide is too distant to form a direct or indirect interaction ([@B12],[@B39]). However, in the env1(2′-dG-II) structure, A77 forms a direct two hydrogen bond interaction with the U22--A52 base pair, establishing a direct base triple between the three joining strands of the junction (Figure [5E](#F5){ref-type="fig"}). The role of this interaction in ligand binding affinity is revealed by an A77U mutation, which disrupts the base triple and weakens 2′-dG binding affinity by ∼7-fold. The equivalent A73C mutation in xpt riboswitch aptamer results in only a two-fold decrease in ligand binding affinity ([@B42]). Thus, the unique insertion element of the 2′-dG-II class promotes two new base-mediated interactions that further organizes the three-way junction at the base of the P3 helix, thereby increasing ligand binding affinity. 2′-Deoxyguanosine recognition by the env1 riboswitch aptamer domain {#SEC3-5} --------------------------------------------------------------------- As with other purine family riboswitches, env1(2′-dG-II) recognizes the ligand nucleobase through a base triple involving a pyrimidine residue at position 51 in J2--3 and a pyrimidine at position 78 in J3--1 (the equivalent positions in xpt are 51 and 74, respectively). C78 forms a Watson--Crick base pair with the 2′-deoxyguanosine nucleobase. Nucleotide 78, which is universally conserved, is essential for high affinity ligand binding; its mutation to adenosine results in 1200-fold weaker binding affinity (Table [2](#tbl2){ref-type="table"}). C51 pairs with the ligand\'s sugar edge, in the same fashion as the equivalent base, C58, in Mfl-IA ([@B11],[@B12]) (Figure [6A](#F6){ref-type="fig"}). Mutation of C51 to uridine results in significant loss of ligand binding affinity (∼18-fold, Table [2](#tbl2){ref-type="table"}), similar to the same mutation in Mfl-IA(2′-dG-I) (83-fold, ([@B12])). Finally, while U47 in xpt directly interacts with U51, the equivalent nucleotide in both classes of 2′-dG riboswitches is positioned within a three base stack and does not play a direct role in ligand binding. Thus, base recognition in 2′-dG-II uses the same set of same contacts as 2′-dG-I and accommodates the 2′-deoxyribose sugar moiety through a shift of C51 towards C74 as compared to the positioning of U51 in guanine and adenine riboswitch aptamers ([@B11],[@B12]). ![Ligand recognition by the env1 2′-dG-II riboswitch aptamer domain. (A) Interactions between nucleotides in the three-way junction and the guanine moiety of the ligand. Hydrogen bonding interactions are shown as grey dashes. Note that two hydrogen bonding interactions are drawn between O2′ of U22 and the N7 and O6 of 2′-dG since these two interactions are nearly equidistant (2.9 and 2.7 Å, respectively). (B) Interactions between the 2′-deoxyribose moiety and RNA. The nucleobase moiety of the 2′-dG ligand (magenta) has been omitted for clarity. (C--E) Base triple between J2/3 and the second proximal base pair in P1 in the (C) env1 2′-dG-II riboswitch, (D) xpt guanine riboswitch and (E) M. florum 2′dG-I riboswitch.](gkz839fig6){#F6} An unusual feature of the 2′-dG-II class relative to other classes in the purine family is the presence of a G21--C79 Watson--Crick base pair in P1 proximal to the three-way junction rather than an A--U pair. While an A--U pair is nearly universally conserved at this position, a G--C pair is observed in a few guanine and adenine riboswitches ([@B43]), and an A--U to G--C mutation is well tolerated by the xpt riboswitch ([@B42]). In env1, this base pair is directly involved in ligand recognition through interactions between N2 of G21 and N4 of C50 hydrogen bonding with the deoxyribose furan oxygen (O4′) (Figure [6B](#F6){ref-type="fig"}). This is an additional hydrogen bonding interaction over that observed in Mfl-IA(2′-dG-I), in which only the exocyclic amine of C57 (equivalent of C50 in env1) interacts with O4′ of 2′-deoxyguanosine. This additional interaction substantially contributes to env1′s higher affinity for 2′-dG than Mfl-IA since a G21A--C79U mutation in env1 binds 2′-dG with 16.9 times lower affinity than wild type (Table [2](#tbl2){ref-type="table"}). The env1(2′-dG-II) aptamer domain accommodates the 2′-deoxyribose sugar through a reorganization of five nucleotides in J2/3 (nt 47--51) relative to the guanine/adenine class in a fashion similar to the 2′-dG-I class. The first key difference is the shift of C51 towards C78, which maintains a two hydrogen bond interaction between C51 and 2′-dG (Figure [6A](#F6){ref-type="fig"}). This shift was first documented in a designed 2′-dG hybrid variant of xpt and Mfl-IA and was proposed to be essential for 2′-dG recognition ([@B11]). The second difference between env1(2′-dG-II) and guanine/adenine aptamers is the stacking of C47, C48 and U49 to create a pocket for the deoxyribose sugar, which is again similar to the configuration both in a designed 2′-dG hybrid variant of the xpt aptamer as well as Mfl-IA. The last nucleotide of the stack (U49) interacts differently with the universally conserved U--A pair in P1 between the three classes (Figure [6C](#F6){ref-type="fig"}--[E](#F6){ref-type="fig"}). U49 forms a single hydrogen bond with U20--A80 pair while the equivalent uridine residue in guanine/adenine riboswitches forms a two hydrogen bond interaction with the U--A pair. In contrast, the equivalent residue in Mfl-IA(2′-dG-I) is a cytosine that does not interact with the U--A pair, but rather interacts with two hydroxyl groups in the backbone. Overall, the env1(2′-dG-II) and Mfl-IA(2′-dG-I) aptamers use a similar strategy to create a binding pocket for the deoxyribose sugar. The 2′-deoxyguanosine sugar is recognized by extensive interactions with the pocket formed by J2/3 and P1. As described above, the furan oxygen (O4′) forms two hydrogen bonding interactions with N2 of G21 and N4 of C50 (Figure [6B](#F6){ref-type="fig"}). The 3′-OH of the ligand is recognized by the 2′-OH of U49, similar to what is observed in Mfl-IA(2′-dG-I). Finally, the 5′-OH of the ligand hydrogen bonds with N3 of G21 and likely N4 of C48. This latter hydrogen bonding interaction is slightly longer at 3.6 Å, but can still be productive. Within the 2′-dG-II class, residue 48 is often adenosine which could also position a hydrogen bond donating amine adjacent to the 5′-OH of 2′-dG. This substitution in env1(C48A) results in a 4.8-fold increase in binding affinity, strongly suggesting that this interaction contributes to binding affinity in other members of the 2′-dG-II class. Remarkably, the binding affinity for env1(C48A) is nearly identical that of the B. subtilis xpt riboswitch aptamer for guanine (7 and 5 nM, respectively) and displays a \>25-fold higher affinity for 2′-dG than Mfl-IA(2′-dG-I) (Table [1](#tbl1){ref-type="table"}). These data indicate that a subset of class II 2′-dG riboswitches have an additional set of interactions that result in significantly higher affinity for their cognate ligand as compared to their 2′-dG-I counterparts. env1 displays modest discrimination between 2′-dG and rG {#SEC3-6} ---------------------------------------------------------- In the cellular context, 2′-dG riboswitches are challenged by chemically similar compounds to their cognate ligand, the most similar being riboguanosine (rG). In rapidly growing E. coli, the intracellular concentration of rG is 1.6 μM as compared to a 2′-dG concentration of 0.57 μM ([@B44]). Measurement of the affinity of env1 for rG revealed that the aptamer binds this metabolite with only a 2.6-fold lower affinity than 2′-dG (Table [1](#tbl1){ref-type="table"}). This contrasts with Mfl-IA, which binds 2′-dG with ∼30-fold (Table [1](#tbl1){ref-type="table"}) to 50-fold ([@B12]) higher affinity than rG. To determine whether other class-II riboswitches exhibit reduced selectivity for 2′-dG over rG, we examined three other 2′-dG-II riboswitches with varying sequences within the three-way junction (Table [1](#tbl1){ref-type="table"}). Overall, class II 2′-dG riboswitches vary broadly in their ability to discriminate between 2′-dG and rG, with env1 being the least selective while the env23 sequence has a far greater selectivity for 2′-dG than Mfl-IA. This range in selectivity is accompanied by a broad range in affinities, varying almost 2 orders of magnitude in 2′-dG binding affinity and approaching 3 orders of magnitude in rG binding affinity. This broad spectrum of binding affinities for the cognate ligand is similar to that observed in other riboswitches, such as the SAM-I riboswitch ([@B45],[@B46]). env1 shows decreased discrimination against antiretroviral 2′-dG derivatives compared to M. florum {#SEC3-7} ------------------------------------------------------------------------------------------------------ In addition to high affinity rG binding, env1 also recognizes more structurally divergent 2′-dG derivatives. Compared to M. florum 2′-dG-I, env1 is more tolerant toward chemically related compounds as demonstrated by its higher binding affinities and weaker discrimination against the antiviral drugs acyclovir and pencyclovir. Env1 binds acyclovir and pencyclovir more tightly (K~D~ = 560 ± 10 nM and 2.0 ± 0.1 μM, respectively) than M. florum (K~D~ = 4.8 ± 1.3 and 22 ± 1.1 μM, respectively), and displays a lowered ability to discriminate between the antiviral and 2′-dG (K~rel,~~env1~~(lig/2′-dG)~ = 16 for acyclovir and 59 for pencyclovir; K~rel,~~M.\ florum~~(lig/2′-dG)~ = 28 for acyclovir and 132 for pencyclovir). Thus, while the env1 riboswitch achieves higher affinity binding for 2′-dG than other riboswitches, it appears that its ability to discriminate between closely related metabolites and RNA-binding drugs is significantly diminished---a noteworthy example that higher affinity binding does not necessarily correlate with higher specificity. DISCUSSION {#SEC4} ========== The structure and associated mutational analysis of a member of the 2′-dG-II class of purine riboswitches in complex with 2′-deoxyguanosine has yielded new insights into how modification of similar RNA sequences can potentially alter selectivity to bind alternative small molecules. The 2′-dG-II riboswitch aptamer domain shares significant sequence and structural homology with other members of the purine riboswitch family in regions critical for establishing global 3D architecture and ligand recognition. Compared to the guanine/adenine class, both classes of 2′-dG binding riboswitches use similar changes in sequence and architecture in J2/3 to accommodate the 2′-deoxyribose sugar: a shift of the pyrimidine residue that contacts the sugar edge of the ligand nucleobase in all purine riboswitches and flipping out of three nucleotides from J2/3. This five nucleotide element (xpt and env1 nucleotides 47--51) is critical for conferring 2′-dG selectivity. A single point mutation, U51C, in the xpt guanine riboswitch is sufficient to switch the ligand preference from guanine to 2′-dG, and additional changes within this element further enhance 2′-dG selectivity and affinity. The two 2′-dG binding classes diverge in how they fully establish both high affinity and selectivity for 2′-dG over guanine beyond differences in J2/3. Structural and mutational analysis of the Mfl-IA(2′-dG-I) RNA revealed that both local and distal differences in the RNA are required to achieve high affinity, selective binding for 2′-dG over guanine ([@B11],[@B12]). These differences include an altered conformation of the 2′-dG-I A33 (A24 equivalent) nucleotide in the three way junction to form a triple at the base of P2 that is not observed in the guanine/adenine and 2′-dG-II classes, as well as an L2-L3 interaction that preserves the G--C Watson--Crick pairs between the loops but differs substantially otherwise. In contrast, the 2′-dG-II class of RNAs appears to exploit only local differences around the ligand binding pocket to achieve high affinity and selective binding of 2′-dG, which is driven in part by a unique two-nucleotide insertion in J3/1. The ability of classes of riboswitches to exploit local changes around the binding pocket to yield differences in ligand binding selectivity has also been observed within the ykkC family of riboswitches. This family contains classes that recognize guanidine, PRPP or ppGpp that are distinguished by sequence and structural differences around and within the junctional binding pocket that include a point substitution and an insertion element (the P1 helix) ([@B47]). Another distinctive feature of the 2′-dG-II class of riboswitches is a broad range of selectivites for 2′-dG over the chemically related compound riboguanosine. While the env1 variant binds 2′-dG with high affinity as compared to other members of the 2′-dG-I and -II classes, it has very low ability to discriminate between these two compounds. Since the concentrations of these two compounds are similar in rapidly dividing E. coli, this raises the distinct possibility that a subset of members of the 2′-dG-II class of riboswitches are responsive to either compound to regulate gene expression. This property was also observed in the 2′-dG-I riboswitches, which was divided into two 'types' based upon experimental analysis of ligand selectivity ([@B10]). The first, exemplified by the Mfl-IA riboswitch, selectively binds 2′-dG over 3′-dG and guanosine, but the type II sequences bind these compounds with similar affinities. Thus, the ability to respond to a larger pool of guanosine metabolites is found within both classes of 2′-dG riboswitches and likely reflects a regulatory need by a subset of genes whose expression is controlled by these riboswitches. The ability of a riboswitch to respond to multiple chemically similar compounds may be fairly common. Examples of this behavior include the glmS riboswitch that can interact with both activating and inhibitory metabolites ([@B51]), the class-II cobalamin riboswitches, some of which bind the biologically active forms of B~12~ with near equal affinities ([@B7]) and THF riboswitches that bind to a spectrum of reduced folates ([@B52],[@B53]). This behavior may enable these riboswitches to respond to metabolic and physiological states of the cell that cannot be readily sensed by interacting with a single compound within a pool of related metabolites. Insights into the structural and ligand binding properties of env1 and other class-II 2′-dG riboswitches potentially provide new avenues for harnessing these RNAs for synthetic biological applications. Synthetic riboswitches derived from natural purine riboswitches have been implemented in diverse bacteria including industrially important strains of cyanobacteria ([@B54]) and thermophiles ([@B55]) to regulate gene expression. Furthermore, it has been shown that the guanine riboswitch can be reprogrammed to recognize pyrimidine ([@B56]) and pterin ([@B27]) compounds with only a limited set of mutations, further diversifying the utility of this riboswitch platform. More recently, it was shown that the purine riboswitch aptamer can be used as an architectural 'scaffold' to evolve radically new binding pockets within the three-way junction for compounds dissimilar to purines such as serotonin and dopamine ([@B26]). The current study suggests how small insertion elements in the purine riboswitch may be leveraged to engineer RNAs responsive to purine-like compounds and proposes potential enhancement of binding affinities by expanding hydrogen-bonding networks in the binding core. As the demand for a diverse set of robust small molecule responsive regulatory systems increases, the purine riboswitch continues to present new opportunities to meet these needs in synthetic biology. DATA AVAILABILITY {#SEC5} ================= Atomic coordinates and structure factors for the reported crystal structure has been deposited in the RCSB PDB ([www.rcsb.org](http://www.rcsb.org)) under the accession number 6P2H. Other data is available upon request. Supplementary Material ====================== ###### Click here for additional data file. We acknowledge the technical support and assistance of Dr Annette Erbse in diffraction and calorimetry experiments. SUPPLEMENTARY DATA {#SEC6} ================== [Supplementary Data](https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkz839#supplementary-data) are available at NAR Online. FUNDING {#SEC7} ======= National Institutes of Health (NIH) \[R01 GM073850 to R.T.B. and T32 GM065103 to M.M.M.\]. Funding for open access charge: NIH. Conflict of interest statement. None declared.
Chakdaha College Chakdaha College, established in 1973, is a college in Chakdaha, in Nadia district, West Bengal, India. It offers undergraduate courses in arts, commerce and sciences. It is affiliated to University of Kalyani. Courses Offered The college is recognized by the University Grants Commission (UGC). References External links Chakdaha College Category:Colleges affiliated to University of Kalyani Category:Educational institutions established in 1973 Category:Universities and colleges in Nadia district Category:1973 establishments in India • Kalyani University result publist Now
Taiwan Becomes First Asian Nation To Legalise Same-Sex Marriage Taiwan Becomes First Asian Nation To Legalise Same-Sex Marriage Taiwan has become the first country in Asia to legalise same-sex marriage. The Taiwanese parliament rejected a last-ditch attempt from conservative lawmakers for a watered down ‘civil-union’ law, according to reports, and comfortably passed a law to allow same-sex couples to enter ‘exclusive permanent unions’. The parliament added a second clause, allowing couples to apply for a ‘marriage registration’ from government agencies. The issue has been the cause of fierce debate on the island nation, dividing parties and members of parliament. Today, however, the country’s top court ruled that not allowing same-sex couples to marry violates the constitution, as per The Guardian. Judges gave the Taiwanese government until Friday next week, May 24, to make changes to the law, or same-sex marriage would be enacted automatically. The government then tabled three bills for debate, the most progressive – and the only one to use the word ‘marriage’ – was passed and backed by gay rights groups. Though it wasn’t as progressive as they hoped, it did offer some adoption rights, and was the closest option to full equality with heterosexual couples. The president recognised how the issue has divided ‘families, generations and even inside religious groups’. However, she added the government’s bill was the only one to respect both the court judgment and the country’s referendum on same-sex marriage. The world is watching to see if Taiwan’s parliament will write a new page in gender equality or deal another blow to Taiwan’s hard-fought democracy, human rights and the rule of law. For the gay communities what matters the most is whether we can legally get married on May 24 and be listed as the spouse in ID cards, to be treated and respected as the ’spouse’ in the whole legal system … and whether same-sex families can obtain legal parental rights for their children. Taiwan will not be altering its existing definition of marriage in civil law, but instead will be enacting a special law for same-sex marriage. Charlie Cocksedge Charlie Cocksedge is a journalist at UNILAD. He graduated from the University of Manchester with an MA in Creative Writing, where he learnt how to write in the third person, before getting his NCTJ. His work has also appeared in such places as The Guardian, PN Review and the bin.
/* * Copyright 2006-2017 the original author or 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. / package com.consol.citrus.jdbc.config.xml; import com.consol.citrus.config.util.BeanDefinitionParserUtils; import com.consol.citrus.db.server.JdbcServerConfiguration; import org.springframework.beans.factory.support.BeanDefinitionBuilder; import org.w3c.dom.Element; /* * @author Christoph Deppisch * @since 2.7.3 / public class JdbcEndpointConfigurationParser { /* * Parse endpoint configuration. * @param endpointConfiguration * @param element */ public void parseEndpointConfiguration(BeanDefinitionBuilder endpointConfiguration, Element element) { JdbcServerConfiguration serverConfiguration = new JdbcServerConfiguration(); if (element.hasAttribute("host")) { serverConfiguration.setHost(element.getAttribute("host")); } if (element.hasAttribute("port")) { serverConfiguration.setPort(Integer.valueOf(element.getAttribute("port"))); } if (element.hasAttribute("database-name")) { serverConfiguration.setDatabaseName(element.getAttribute("database-name")); } if (element.hasAttribute("max-connections")) { serverConfiguration.setMaxConnections(Integer.valueOf(element.getAttribute("max-connections"))); } endpointConfiguration.addPropertyValue("serverConfiguration", serverConfiguration); BeanDefinitionParserUtils.setPropertyValue(endpointConfiguration, element.getAttribute("timeout"), "timeout"); BeanDefinitionParserUtils.setPropertyValue(endpointConfiguration, element.getAttribute("auto-connect"), "autoConnect"); BeanDefinitionParserUtils.setPropertyValue(endpointConfiguration, element.getAttribute("auto-create-statement"), "autoCreateStatement"); BeanDefinitionParserUtils.setPropertyValue(endpointConfiguration, element.getAttribute("auto-transaction-handling"), "autoTransactionHandling"); BeanDefinitionParserUtils.setPropertyReference(endpointConfiguration, element.getAttribute("auto-handle-queries"), "autoHandleQueries"); BeanDefinitionParserUtils.setPropertyValue(endpointConfiguration, element.getAttribute("polling-interval"), "pollingInterval"); BeanDefinitionParserUtils.setPropertyReference(endpointConfiguration, element.getAttribute("message-correlator"), "correlator"); } }
A convicted murderer who knocked out a student’s teeth in McDonald’s admitted trying to sabotage his trial. Paul Branchflower was jailed for life with a minimum of 13 years behind bars after running over Glynn Ellis, 46, in Manchester in 2002. He convinced a parole board he was no longer a risk and was let out on day release, only to attack Ross Stephenson in Liverpool in 2014. Branchflower stood trial over the incident, but it collapsed after a woman called Christina Gregson contacted Mr Stephenson on Facebook. She suggested a police investigation into the assault at the Lord Street... read more Related news A care worker at a North Wales psychiatric unit has admitted trying to get a woman with a mental disorder to engage in sexual activity. Defendant Jason Paul Williams, 44, will be sentenced after his trial for a series of other offences involving the... A convicted murderer who knocked a student’s teeth out at Liverpool’s city centre McDonald’s while out on day release was sent back to prison. Paul Branchflower, 32, was jailed for life with a minimum of 13 years behind bars after running over Glynn... Two council workers have been given bravery awards for tackling a thug who attacked a student. Drain cleaners Ian McPherson, 49, and Paul Heaton, 43, were working in Upper Brook Street in the city centre when they saw a man walk up to a student and... Police have warned they can’t deploy ‘sufficient numbers’ of officers to always tackle rowdy student parties in Fallowfield. University bosses have opposed a request by residents to make students pay a levy to fund £400,000-a-year night patrols in the... Comedian Alan Carr’s manager was seriously assaulted outside a late-night McDonald’s restaurant after trying to stop fans taking photos of the star. Elliott Andrews was attacked by Jaleel Burman on Lord Street in the city centre after getting wound up... A thug attacked a volunteer trying to help vulnerable people in the Gay Village. Lee Macintosh was part of the Lesbian and Gay Foundation’s ‘Village Angel’ scheme, who wear pink tabards and try and stop people from falling victim to crime on nights...
A neurovascular flap for coverage of distal plantar defects. Ulcers on the sole of the foot are very uncomfortable. A poor blood supply and a tendency to slow healing are common in these patients. Because of its weight-bearing and unique sensory function the glabrous skin of the sole is very specialized. To obtain a functional skin coverage, glabrous skin with a good blood supply and an intact nerve supply may be superior to other methods of soft tissue reconstruction. A neurovascular axial or island flap from the fibular side of the great toe may fulfill this demand with minimal donor site morbidity. Three cases are reported and the literature on the subject is summarized.
Cross Lake (Moore Creek) Cross Lake is a lake in South Algonquin, Nipissing District, Ontario, Canada, about south of the community of Madawaska. Highway 523 runs just east of the lake, and the settlement of Cross Lake lies between the highway and the lake. Hydrology Cross Lake is in the St. Lawrence River drainage basin, is about long and wide and lies at an elevation of . The name refers to its roughly cross-like shape, with one line running from the northwest to southeast, and the other from west-southwest to east-northeast. There are four unnamed creek inflows, one at the west, one at the south, one at the north from Lyell Long Lake and one at the southeast from Hawk Lake. The primary outflow, at the southwest, is Moore Creek towards McKenzie Lake, which flows into the Madawaska River, and via the Ottawa River into the St. Lawrence River. See also List of lakes in Ontario References Category:Lakes of Nipissing District
S.G. Thomas and S. Huang contributed equally to this paper. Abbreviations used in this paper: CD, cytochalasin D; F-actin, filamentous actin; G-actin, globular actin; GM, germination medium; Jasp, jasplakinolide; LatB, latrunculin B; PCD, programmed cell death; ROS, reactive oxygen species; SI, self-incompatibility. Introduction ============ Self-incompatibility (SI) is one of the systems that prevent self-fertilization in flowering plants. SI is controlled by a multiallelic S locus; S-specific pollen rejection results from the interaction of pollen S and pistil S determinants that have matching alleles ([@bib8]). In Papaver rhoeas, the pistil S proteins ([@bib7]) act as ligands, triggering increases in the cytosolic-free calcium concentration (\[Ca^2+^\]~i~) in incompatible pollen ([@bib9], [@bib10]). The Ca^2+^-mediated signaling network results in the rapid inhibition of incompatible pollen tube growth. Within a few minutes of SI signals, reorganization and massive, sustained depolymerization of the pollen filamentous actin (F-actin) is induced ([@bib12]; [@bib39]). Although the extent of F-actin depolymerization during SI is clearly sufficient to inhibit pollen tube growth, it appears to be a gross excess over the amount required to achieve this. This suggested possible additional functions for the alteration to actin dynamics. Unwanted cells are usually removed by programmed cell death (PCD). Many examples of PCD in plant development ([@bib25]) and in responses to external stimuli ([@bib43]; [@bib6]; [@bib17]; [@bib45]) have been documented. Features of PCD in animal cells include cytochrome c leakage from the mitochondria, DNA fragmentation, and caspase activation. In animal cells, apoptosis is mediated by a caspase cascade. Activated caspases cleave numerous substrates, including endogenous nuclease inhibitors, resulting in the fragmentation of nuclear DNA. Although PCD should theoretically involve a caspase-3--like activity, no caspase homologues have been found in plants ([@bib47]). Despite this, there is good evidence for caspase-like activities in plant cells ([@bib27]; [@bib36]). We recently reported that SI triggers a PCD cascade in incompatible P. rhoeas pollen, which involves a caspase-3--like activity ([@bib44]). This provides a precise mechanism for the specific destruction of incompatible pollen. As the actin cytoskeleton is a major target and effector of signaling cascades in both animal and plant cells ([@bib37]; [@bib41]), we explored a possible role for actin depolymerization in signaling to PCD. Recent evidence suggests that either stabilization or depolymerization of the actin cytoskeleton is adequate to induce PCD in yeast and some animal cells, depending on the cell type ([@bib28]; [@bib19]; [@bib23]; [@bib33]; [@bib29]; [@bib16]; for review see [@bib15]). It is postulated that the alteration of actin filament dynamics initiates or modulates the apoptotic signaling cascade ([@bib19]; [@bib23]; [@bib33]; [@bib29]; [@bib16]), thereby committing cells to die (for review see [@bib15]). Because PCD is triggered by SI in incompatible P. rhoeas pollen ([@bib44]), we hypothesized that early SI-induced actin depolymerization might play a role in acting as an upstream component in PCD activation. We have investigated this possibility using specific drugs to alter actin polymerization status in pollen tubes. Results ======= Jasplakinolide stabilizes actin filaments and alleviates SI-induced PCD ----------------------------------------------------------------------- Pollen tubes have a characteristic F-actin organization ([Fig. 1 A](#fig1){ref-type="fig"}), and SI induces the rapid depolymerization of actin filaments and bundles ([Fig. 1 B](#fig1){ref-type="fig"}). To test the hypothesis that SI-stimulated PCD is triggered by actin depolymerization, we used jasplakinolide (Jasp), which stabilizes actin filaments and stimulates polymerization ([@bib1]; [@bib2]) and has been shown to inhibit pollen tube growth ([@bib3]). We found that 0.5 μM Jasp disrupted P. rhoeas pollen tube actin organization, which induced actin filament bundling and aggregation ([Fig. 1 C](#fig1){ref-type="fig"}), and inhibited tip growth (unpublished data). The effect of Jasp on actin organization was essentially the opposite of that induced by SI. ![*Jasp alters actin organization and alleviates PCD induced by SI in P. rhoeas* pollen tubes.** (A) Rhodamine-phalloidin staining shows normal organization of F-actin in an untreated P. rhoeas pollen tube. (B) Rhodamine-phalloidin staining shows major disruption of F-actin after 10 min of SI induction. (C) Immunolocalization of actin alterations induced by 0.5 μM Jasp for 10 min shows dramatic rearrangement and stabilization of actin filaments. (D) DNA fragmentation, detected by TUNEL labeling, in a pollen tube treated with 1 μM LatB for 10 min. DAPI staining (right) shows that the TUNEL-positive signal (left) corresponds to nuclear DNA. (E) A typical control pollen tube shows no TUNEL-positive signal (left) corresponding to nuclear DNA (right) despite overexposure revealing the background signal. Bars, 10 μm. (F) Induction of SI for 30 min produced high levels of DNA fragmentation, which was only slightly lower than that achieved by an 8-h treatment (SI, 8 h). Consecutive (CON) treatment, in which 0.5 μM Jasp was added for 20 min to pollen tubes that had previously been treated for 10 min with S proteins, significantly reduced the level of DNA fragmentation. Simultaneous (SIM) treatments of SI and Jasp for 30 min also significantly reduced levels of DNA fragmentation. Untreated pollen tubes (control) produced low levels of DNA fragmentation, whereas 0.5 μM Jasp treatment for 30 min produced higher levels than controls but lower than those induced by 30 min of SI. Values are mean percentages ± SEM (error bars; n = 3).](jcb1740221f01){#fig1} We examined whether transient treatments with Jasp might "rescue" SI-induced pollen from PCD by counteracting the actin depolymerization. One of the hallmark features of PCD, DNA fragmentation, is triggered by SI and involves a caspase-3--like activity ([@bib44]). This was used as a marker for PCD and was assessed using TUNEL ([Fig. 1, D and E](#fig1){ref-type="fig"}). The induction of SI, which is caused by exposing incompatible pollen to S proteins for 30 min, produced high levels of DNA fragmentation of 55.2%, which was only slightly lower than levels of 65.4% induced by SI for 8 h and significantly different from control levels of 16.8% (P \< 0.001; [Fig. 1 F](#fig1){ref-type="fig"}). These data indicated that the interaction of incompatible pollen with S proteins for 30 min was sufficient to trigger PCD. As we had previously demonstrated that 10 min of SI stimulated a 65% reduction in F-actin levels ([@bib39]), we allowed SI to progress for 10 min to ensure that a significant level of actin depolymerization had occurred and then added 0.5 μM Jasp for 20 min (see Pollen treatments). This consecutive treatment significantly reduced DNA fragmentation ([Fig. 1 F](#fig1){ref-type="fig"}) by 32% (P = 0.04). Simultaneous treatment with SI and Jasp for 30 min also resulted in significantly reduced levels of DNA fragmentation (33.8%; P \< 0.001; [Fig. 1 F](#fig1){ref-type="fig"}). This demonstrates that Jasp can alleviate SI-induced PCD. These data indicate that the actin depolymerization triggered by SI plays a functional role in the initiation phase of PCD in pollen tubes. Latrunculin B reduces the level of F-actin in P. rhoeas pollen ---------------------------------------------------------------- To further investigate whether actin polymerization status is involved in the initiation of PCD in pollen, we attempted to mimic the actin depolymerization induced by SI without the involvement of other SI initiation signals, such as changes to \[Ca^2+^\]~i~. To clarify whether actin depolymerization itself could induce PCD, latrunculin B (LatB; [@bib40]; [@bib5]) was used to depolymerize the actin cytoskeleton in growing P. rhoeas pollen tubes. LatB caused the rapid disruption of F-actin organization ([Fig. 2, A and B](#fig2){ref-type="fig"}) and the inhibition of pollen tube growth (unpublished data). To confirm actin depolymerization, we measured F-actin levels ([@bib14]; [@bib39]) after 10 min of LatB treatments. LatB caused the depolymerization of pollen tube actin filaments in a concentration-dependent manner ([Fig. 2 C](#fig2){ref-type="fig"}). Treatment with 0.1, 1, and 10 μM LatB caused significant reductions (P \< 0.001) in F-actin levels when compared with controls. Treatment with 1 μM LatB, which induced 61.5% F-actin depolymerization, gave a similar reduction to that stimulated by SI (69%; [@bib39]). ![LatB and Jasp induce DNA fragmentation. (A) Rhodamine-phalloidin staining of F-actin organization in a normally growing pollen tube. (B) Rhodamine-phalloidin labeling of a pollen tube treated with 1 μM LatB for 10 min showing the reorganization and depolymerization of F-actin. Bars, 10 μm. (C) Treatment of growing pollen tubes with LatB for 10 min caused the concentration-dependent depolymerization of F-actin. Data are mean F-actin levels ± SEM (error bars) as a percentage of the DMSO controls (n = 3). (D) Treatment with LatB for 8 h triggered DNA fragmentation. DMSO controls showed only low levels of DNA fragmentation. (E) Treatment with Jasp for 8 h triggered DNA fragmentation. (D and E) Data are mean percentages of TUNEL-positive nuclei ± SEM from four (D) or three (E) independent experiments.](jcb1740221f02){#fig2} Actin depolymerization is sufficient to induce PCD -------------------------------------------------- To test whether LatB-induced actin depolymerization could trigger PCD, pollen tubes were treated with LatB, and levels of DNA fragmentation were assessed after 8 h. LatB stimulated DNA fragmentation in a concentration-dependent manner ([Fig. 2 D](#fig2){ref-type="fig"}). The incidence of DNA fragmentation at all concentrations of LatB was significantly different from control pollen tubes (P \< 0.001) and increased from 6.9% in controls to 30.7% in the presence of 0.01 μM LatB and to 75.8% with 10 μM LatB ([Fig. 2 D](#fig2){ref-type="fig"}). Assuming that LatB does not have side effects, this indicated that actin depolymerization triggered DNA fragmentation independently of other SI signals. We also examined whether actin filament stabilization or net assembly of filaments from the profilin--actin pool might also induce PCD in pollen. Jasp stimulated DNA fragmentation in a concentration-dependent manner ([Fig. 2 E](#fig2){ref-type="fig"}). The incidence of DNA fragmentation in Jasp-treated pollen tubes increased from 10.4% in control samples to 58% in the presence of 1 μM Jasp ([Fig. 2 E](#fig2){ref-type="fig"}). As Jasp binds the phalloidin-binding site of actin, we could not quantify actin polymer levels for these treatments. Given the assumptions regarding the lack of Jasp and LatB side effects, the results indicate that changes in actin filament dynamics can induce DNA fragmentation. A hallmark feature of apoptosis and PCD is the involvement of caspases, which are responsible for initiating and executing cell death. We showed previously that SI-induced PCD is mediated by a caspase-3--like/DEVDase activity ([@bib44]). Therefore, we tested whether the DNA fragmentation stimulated by LatB and Jasp involved such an activity. We used the tetrapeptide Ac-DEVD-CHO (DEVD), which is a caspase-3 inhibitor ([@bib11]; [@bib34]; [@bib6]; [@bib44]). Pollen was pretreated with either DEVD or the caspase 1 inhibitor Ac-YVAD-CHO (YVAD), which acts as a negative control, for 1 h before the addition of LatB or Jasp for 8 h. Pollen tubes pretreated with DEVD had significant (65.1--71.6%) reductions in the levels of DNA fragmentation compared with controls without pretreatment (P \< 0.001; [Fig. 3 A](#fig3){ref-type="fig"}). Pretreatment with YVAD had no significant effect on the levels of DNA fragmentation induced by LatB or Jasp (P = 0.2; [Fig. 3 A](#fig3){ref-type="fig"}). Because DEVD can prevent LatB- or Jasp-induced DNA fragmentation, this implies that both actin depolymerization and stabilization or polymerization can stimulate the activation of a caspase-like enzyme upstream of DNA fragmentation. These data indicate that changes in actin filament dynamics are sufficient to induce a caspase-like (DEVDase) activity that results in PCD in pollen. ![Alterations in the actin polymerization status trigger a caspase-like/DEVDase activity upstream of DNA fragmentation. (A) LatB- and Jasp-induced DNA fragmentation is dependent on a caspase-like/DEVDase activity. LatB and Jasp (white bars) induced high levels of DNA fragmentation. Pretreatment with DEVD significantly reduced the levels of DNA fragmentation (black bars), whereas pretreatment with YVAD (crosshatched bars) had no significant effect on DNA fragmentation induced by LatB and Jasp. (B) DEVD significantly reduced levels of DNA fragmentation in pollen tubes treated with LatB. (A and B) Data are mean percentages of TUNEL-positive nuclei ± SEM (error bars) from three independent experiments. (B and C) Untreated pollen, white bars; + 1 μM LatB for 10 min, black bars; + 1 μM LatB for 60 min, crosshatched bars. (C) DEVD had no effect on LatB-induced actin depolymerization induced in growing pollen tubes; similar levels of F-actin were measured in the presence and absence of DEVD. Data are means ± SEM from four independent experiments.](jcb1740221f03){#fig3} Transient F-actin depolymerization is sufficient to induce PCD -------------------------------------------------------------- To examine whether transient changes in actin filament levels or dynamics could serve as a signal involved in the initiation of PCD or whether sustained alterations are required, "washout" experiments were conducted using LatB treatments, as this most closely mimicked the effect of SI. Pollen tubes were treated with 0.1 and 1 μM LatB for 10 or 60 min, after which the drug was washed out and the incidence of DNA fragmentation was assessed. Actin filament levels were determined at the end of the LatB incubation period to demonstrate that depolymerization had taken place and also after washouts to establish whether repolymerization had occurred. As expected, F-actin levels were reduced in a concentration- and time-dependent manner ([Table I](#tbl1){ref-type="table"}). The level of actin polymer after treatment with 0.1 μM LatB was reduced by 23.0% (P = 0.03) at 10 min and was further reduced by 50.2% (P \< 0.001) by 60 min. The higher concentration of 1 μM LatB reduced actin levels by 53.1% (P \< 0.001) at 10 min and by 69.2% (P \< 0.001) at 60 min. After washouts, with the exception of the 1-μM 60-min treatment, F-actin levels returned to similar levels as found in untreated pollen, demonstrating that F-actin was only depolymerized transiently ([Table I](#tbl1){ref-type="table"}). Pollen tubes treated with 0.1 μM LatB also resumed normal growth (unpublished data). ###### Quantification of actin polymer level and DNA fragmentation --------------------------------------------------------------------------------------------------------- Treatment Actin polymer level at\ Actin polymer level\ Percent TUNEL-positive nuclei end of treatment after washing ------------------------ ------------------------- ---------------------- ------------------------------- DMSO 100 100 16.4 ± 1.4 0.1 μM LatB for 5 min ND ND 19.5 ± 2.2 0.1 μM LatB for 10 min 77.0 ± 8.9 125.9 ± 7.3 24.3 ± 0.6 0.1 μM LatB for 30 min ND ND 57.1 ± 8.2 0.1 μM LatB for 60 min 49.8 ± 5.5 107.3 ± 9.0 64.0 ± 4.0 1 μM LatB for 5 min ND ND 58.5 ± 9.9 1 μM LatB for 10 min 46.9 ± 3.8 93.5 ± 10.1 56.4 ± 11.8 1 μM LatB for 30 min ND ND 68.2 ± 6.2 1 μM LatB for 60 min 30.8 ± 4.2 70.1 ± 5.2 70.5 ± 6.3 --------------------------------------------------------------------------------------------------------- Results are means ± SEM (n = 3). The actin polymer level is expressed as a percentage of the amount measured in the control (i.e., control is 100%). TUNEL data are expressed as the percentage of nuclei showing TUNEL labeling. DNA fragmentation correlated with the duration and extent of actin depolymerization. After 5- and 10-min treatments with 0.1 μM LatB, the effects were similar, and only small increases in DNA fragmentation were detected (P = 0.3; NS; [Table I](#tbl1){ref-type="table"}). With longer treatments of 0.1 μM LatB, DNA fragmentation increased to 57.1% at 30 min (P = 0.02) and to 64.0% at 60 min (P = 0.001). The 1-μM LatB treatments induced higher levels of DNA fragmentation than those found in the controls for all four time points (P \< 0.001). However, there was no significant difference between the four treatments (P = 0.6; [Table I](#tbl1){ref-type="table"}), indicating that a threshold level of DNA fragmentation had been triggered. Taking these F-actin quantification and DNA fragmentation data into account, reducing F-actin levels to ∼50% for either 10 or 60 min gave a high incidence of DNA fragmentation even though F-actin levels returned to normal after washing. This indicates that during a brief 10-min period of actin depolymerization to this level, an irreversible "decision-making" step is made, pushing pollen into PCD. Because a DEVDase/caspase-like activity is involved, this implicates actin depolymerization in PCD initiation. Treatments that did not reduce F-actin to this level (e.g., 0.1 μM LatB for 10 min) had a low incidence of DNA fragmentation (24.3%), which was only slightly higher than the control level (P = 0.02). Therefore, we can say with some confidence that here, the reduced incidence of DNA fragmentation was the result of a transient actin depolymerization that was insufficient to cause PCD. Thus, the threshold for PCD induction is somewhere between a 23 and 46.9% reduction in F-actin levels for as little as 10 min. Our data indicate that \<50% actin depolymerization for 10 min is sufficient to induce PCD, achieving levels of DNA fragmentation very similar to that induced by 8 h of LatB (P = 0.4; NS). Notably, this threshold level of actin depolymerization required to initiate PCD using LatB is somewhat lower than the 58 and 69% reduction in F-actin levels resulting from 5- and 10-min SI inductions, respectively ([@bib39]). LatB-induced PCD is mediated by a caspase-3--like activity ---------------------------------------------------------- As LatB treatments appeared to mimic the SI--PCD response, we examined whether LatB-induced DNA fragmentation relied on a caspase-like/DEVDase activity similar to that induced by SI ([@bib44]). DNA fragmentation was normally induced by 1-μM LatB treatments, whereas DEVD pretreatment prevented this ([Fig. 3 B](#fig3){ref-type="fig"}), and levels of DNA fragmentation were not significantly different from untreated samples (P = 0.13). These data provide strong evidence that even quite transient LatB-induced actin depolymerization is sufficient to induce a caspase-3--like/DEVDase activity upstream of DNA fragmentation. Because DEVD had no significant effect on the amount of actin depolymerization caused by LatB ([Fig. 3 C](#fig3){ref-type="fig"}), this established that DEVD does not interfere with the action of LatB. We have also used the caspase-3 substrate Ac-DEVD-AMC to establish this caspase-like activity more directly. Pollen tubes treated with 1 μM LatB for 6 h exhibited an increase in DEVDase activity of 54 ± 5% (n = 4) compared with control samples containing germination medium (GM) only. This level of caspase activity was similar to that induced by either SI or 0.5-μM Jasp treatments (unpublished data). Thus, LatB-stimulated pollen extracts exhibited markedly increased levels of caspase-3--like activity, indicating cleavage of the substrate by a DEVDase activity. The activation of caspases commits the cell to die; therefore, our data implicate alterations in actin depolymerization as playing a functional role in stimulating or regulating the PCD cascade in pollen. Inhibition of tip growth does not induce PCD in pollen tubes ------------------------------------------------------------ Because both LatB and Jasp inhibit tip growth ([@bib14]; [@bib46]; [@bib39]; [@bib3]), we wished to establish that PCD induction was not indirectly caused by the cessation of tip growth. We used caffeine, which perturbs tip growth ([@bib31]) but does not affect the actin cytoskeleton of pollen tubes ([@bib12]; [@bib39]). Pollen tubes treated with 3 mM caffeine for 10 or 60 min did not significantly alter F-actin levels compared with controls (112 ± 12 and 112 ± 2%, respectively; n = 3; P = 0.06). Caffeine-treated pollen tubes had low DNA fragmentation levels that were not significantly different from controls (15 ± 3% at 10 min, P = 0.2; and 23 ± 4% at 60 min, P = 0.06; n = 3). This demonstrates that the LatB/Jasp-induced DNA fragmentation is not merely a consequence of the inhibition of growth but is caused by changes in actin polymer levels or assembly dynamics. Jasp counteracts LatB-induced PCD --------------------------------- We also investigated whether counteracting the effect of LatB-induced depolymerization with Jasp might prevent progression into PCD. Pollen tubes were treated in a similar manner to the SI experiment. They were first treated with 0.1 μM LatB for 10 min to ensure that actin depolymerization had occurred; 0.5 μM Jasp was then added for 20 min, after which the drugs were washed out. Thus, the total length of time that the pollen was exposed to LatB for this consecutive treatment was 30 min. This treatment resulted in a 45% reduction (P = 0.002) in the level of DNA fragmentation compared with LatB alone for 30 min ([Fig. 4](#fig4){ref-type="fig"}). We also performed treatments whereby LatB and Jasp were added simultaneously; this had a similar significant effect with a 51.7% (P = 0.007) reduction in the incidence of PCD to 19.8%, which was not significantly different (P = 0.2) from control levels of 11.3% ([Fig. 4](#fig4){ref-type="fig"}). These data show that Jasp can counteract the actin depolymerization induced by LatB and, thereby, rescues pollen from entry into PCD. ![Actin depolymerization induces PCD, which can be alleviated by altering the actin polymerization status. The effect of counteracting LatB-induced depolymerization with Jasp was assessed by the extent of DNA fragmentation. Untreated pollen tubes (control) produced low levels of DNA fragmentation; treatment with 0.1 μM LatB for 30 min produced increased levels of DNA fragmentation, and 0.5 μM Jasp for 30 min produced increased but lower levels of DNA fragmentation. With combined LatB-Jasp treatments (consecutive \[CON\] treatments \[10 min with 0.1 μM LatB and then 0.5 μM Jasp for a further 20 min\] and simultaneous \[SIM\] treatments \[0.1 μM LatB and 0.5 μM Jasp for 30 min\], the level of DNA fragmentation was significantly reduced compared with that observed with LatB or Jasp alone. Data are mean percentages of TUNEL-positive nuclei ± SEM (error bars) from four independent experiments.](jcb1740221f04){#fig4} Discussion ========== The actin cytoskeleton has been identified as a major target and effector of signaling cascades in both animal and plant cells ([@bib37]; [@bib41]). SI may be viewed as the triggering of a signaling cascade that takes the cell into PCD. In this study, we provide the first account of a causal link between actin polymer levels or dynamics and the initiation of PCD in a plant cell. Our study provides a significant advance in our understanding of the mechanisms involved in early SI and of the initiation of PCD in plant cells because very little is known about the early events involved in PCD in plants. Our data provide evidence that relatively transient but substantial F-actin depolymerization can trigger PCD, which is mediated by a caspase-3--like activity. We previously demonstrated that the SI response in P. rhoeas pollen results in a 69% reduction in F-actin levels within 10 min ([@bib39]) and, independently, that SI also induces PCD ([@bib44]). In this study, we have demonstrated that a transient reduction in F-actin levels of \<50%, which is independent of SI induction, is sufficient to induce PCD. This provides evidence for a link between the signaling cascades involving actin dynamics and PCD, showing that actin depolymerization is sufficient to induce a caspase-like/DEVDase activity resulting in PCD. Furthermore, together with previous data ([@bib39]), they demonstrate that during an incompatible SI response, the degree of actin depolymerization is more than adequate to act as an intermediary signal to PCD. Because Jasp can alleviate SI-induced DNA fragmentation, presumably by interfering with or counteracting the actin depolymerization induced by SI, this provides further, more direct evidence for the involvement of actin depolymerization in SI-induced PCD. Thus, rapid depolymerization of the actin cytoskeleton induced by SI not only inhibits pollen tip growth but also acts upstream of a signaling cascade that is involved in initiating PCD. Our data support the hypothesis that the F-actin depolymerization and PCD observed during SI function together in a signaling network that prevents incompatible pollen from affecting fertilization. Although LatB or cytochalasin D (CD) has previously been reported to implicate actin depolymerization in PCD during embryogenesis in plants ([@bib38]), the drug treatments extended over a long period of time (6 d), and disruption of the actin cytoskeleton for this length of time will almost certainly result in defects in embryogenesis; this in itself could result in PCD. Thus, although the data suggested a possible involvement of the actin cytoskeleton in PCD, they provided no clear evidence for a functional role for actin depolymerization in PCD. Our findings establish a fundamentally important role for the actin cytoskeleton as a sensor of cellular stress that is common to many eukaryotic cells, as various links between changes in actin dynamics and PCD induction have previously been reported for animals and yeast ([@bib28]; [@bib19]; [@bib23]; [@bib42]; [@bib29]; [@bib16]). Several studies have shown that alterations to the actin cytoskeleton (either stabilization or depolymerization, depending on the cell type involved) can play a functional role as an effector in the initiation of PCD. For example, CD resulted in DNA fragmentation and caspase-3 activity in Jurkat T cells and hippocampal neurons ([@bib42]), and Jasp enhanced and accelerated apoptosis induced by cytokine withdrawal in the IL-2--dependent T cell line CTLL-20 and induced a caspase-3 activity ([@bib32]). Because these data demonstrate that presumed changes to actin polymer levels or dynamics can stimulate caspase-3 activity, which is an effector caspase triggered early in PCD, they provide evidence that actin depolymerization or stabilization is sufficient to act as an intermediary signal early in the PCD signaling cascade. Other studies in yeast and some mammalian cells have also shown that decreasing actin filament turnover (by using Jasp to stabilize actin) induces apoptosis ([@bib32]; [@bib33]; [@bib30]; [@bib16]). Thus, it has been proposed that altering actin dynamics or the rates of assembly and disassembly rather than the level of polymeric actin in cells is sufficient to signal the initiation of apoptosis ([@bib19]; [@bib23]; [@bib33]; [@bib42]; [@bib30]; [@bib4]; [@bib22]; [@bib29]; [@bib16]; for review see [@bib15]). Interestingly, although actin stabilization stimulates PCD in yeast, actin depolymerization has the reverse effect, leading to increased viability ([@bib16]), which is not the case in pollen. This suggests that although there are clear parallels, the specific mechanisms are likely to differ between plants, animals, and yeast. This is borne out by several studies with mammalian cells, in which actin depolymerization can induce or promote apoptosis ([@bib23]; [@bib32]; [@bib42]; [@bib4]; [@bib29]), whereas actin stabilization can inhibit or delay apoptosis ([@bib23]; [@bib13]). Indeed, it has been shown in Jurkat T cells that either increased actin depolymerization or polymerization using CD or Jasp can enhance apoptosis ([@bib32]; [@bib29]). This appears to be the situation in pollen, in which either LatB or Jasp can induce PCD. Furthermore, it has recently been shown that Jasp can alleviate apoptosis in ischemic kidney cells; ischemia normally correlates with a substantial depolymerization of the actin cytoskeleton ([@bib13]). Similarly, phalloidin treatment, which stabilizes F-actin, prevented cisplatin-mediated actin depolymerization and apoptosis in porcine kidney proximal tubule cells ([@bib24]). This is exactly what we have demonstrated here; Jasp effectively reverses the effects of S-protein treatment, presumably by stabilizing actin filaments against depolymerization or counteracting the calcium-induced disassembly. Therefore, it would appear that a precise level of actin polymer or exact flux of subunits through the polymer pool is necessary for normal growth and cell viability of pollen ([@bib14]; [@bib46]); when this is substantially perturbed, PCD is initiated. It has been proposed that it is the alteration of actin dynamics (i.e., the rate of actin polymerization and depolymerization) that modulates the transduction of the apoptotic signal ([@bib29]). The alterations to actin providing the sensory mechanism could involve either changes in polymer levels, changes in the flux of actin through the filament pool, or both. However, although in some mammalian cells, alterations to F-actin status alone (either polymerization or depolymerization, depending on the cell type) are sufficient to induce apoptosis, in other cell types, other apoptotic stimuli are required in addition to drug treatments affecting actin dynamics ([@bib23]; [@bib32]; [@bib29]). Thus, there are likely to be quite important and subtle differences in the mechanisms operating to initiate apoptosis/PCD in different cell types. One notable and important difference between plant pollen and yeast or mammalian cells is the high ratio of globular actin (G-actin) to F-actin in actively growing cells. Measurements from maize and P. rhoeas pollen indicate that just 5--10% of the total actin protein is present in the filamentous form ([@bib14]; [@bib39]). In comparison, budding yeast cells are considered to have the majority of the total actin pool in filamentous form ([@bib21]). These observations further suggest that certain differences in apoptosis initiation and/or responses to cytoskeletal drugs may relate to the endogenous balance between monomer and polymer in different eukaryotic cells. Importantly, our study, which used washouts to achieve short-term actin depolymerization or stabilization, is, to our knowledge, the first to demonstrate that transient (10--60 min) alterations to actin dynamics can trigger PCD. Most of the aforementioned studies have used rather long-term treatments with Jasp or LatB for between 8 and 48 h to induce apoptosis ([@bib32]; [@bib42]; [@bib16]). To our knowledge, this is the only study to quantify the changes in F-actin levels required to trigger PCD. Only two other studies attempted to quantify the actin polymerization status ([@bib33]; [@bib29]). One of these studies reports that measurements after CD treatment of CTLL-20 and Jurkat T cells indicated an increase in the amount of monomeric or G-actin and a decrease in the amount of F-actin, suggesting the promotion of actin filament disruption and depolymerization ([@bib29]). However, no data are shown. The other study ([@bib33]) measured G- and F-actin levels after camptothecin-induced apoptosis in HL-60 cells and found that G-actin was decreased in TUNEL-negative cells at 2 h, indicating that polymerization was increased early in apoptosis. In TUNEL-positive cells (in which PCD had already occurred), G-actin levels were increased, indicating depolymerization. These data are consistent with camptothecin- and Jasp-induced actin polymerization occurring before PCD. Our data go further than this because we have estimated the levels of actin depolymerization required to induce PCD in pollen. In this study, we show that 50% depolymerization of the actin cytoskeleton for just 10 min is sufficient to trigger substantial numbers of cells to undergo PCD. The alterations to actin could involve either changes in polymer levels, changes in the flux of actin through the filament pool, or both. Because virtually no biochemical analysis of actin dynamics leading to PCD has been performed, it would be of considerable interest to establish which mechanisms are involved and whether they vary depending on cell type. Similarly, several different actin-binding proteins have been suggested to play a role during the initiation or execution phases of PCD, but cause and effect relationships are difficult to decipher. We recently identified pollen gelsolin, PrABP80, which is a calcium-stimulated actin filament severing and depolymerizing protein that could potentially be involved in SI-mediated actin depolymerization ([@bib18]). This is of interest, as gelsolin is implicated in modulating apoptosis in animal cells (for review see [@bib26]). How exactly actin polymerization status can affect apoptosis induction is not yet established in any organism. However, there is evidence that changes to actin dynamics interact with apoptotic signaling cascades. It has been suggested that disruption of the cytoskeleton might promote the release of caspases, enabling their activation or, alternatively, disrupting mitochondria and causing the release of cytochrome c, caspases, or caspase activators ([@bib42]). In mammalian cells, there is evidence that either actin depolymerization ([@bib42]) or stabilization ([@bib32]; [@bib4]; [@bib13]) can induce caspase-3 activation; actin depolymerization using CD has been shown to regulate nitric oxide--stimulated apoptosis by modulating PI3-kinase, PKC, and MAPK signaling ([@bib22]). In yeast, it has been proposed that the actin cytoskeleton could act as a regulator for reactive oxygen species (ROS) release from mitochondria, as Jasp can stimulate changes in the levels of ROS ([@bib16]). We have shown here that actin depolymerization or polymerization is sufficient to induce a caspase-3--like activity in pollen. Whether ROS is involved in SI is not yet known, but it is known that the rapid disruption of mitochondria is triggered by SI ([@bib44]). Furthermore, we have previously shown that a MAPK, p56, is activated by SI ([@bib35]). These provide possible targets for signaling links between the actin cytoskeleton and PCD in pollen. Thus, our data clearly demonstrate that actin acts as a sensor for signals and that its dynamics play a key role in signaling to initiate PCD in plant cells. Materials and methods ===================== Pollen treatments ----------------- Pollen of P. rhoeas, the field poppy, was germinated and grown in vitro in liquid GM (0.01% H~3~BO~3~, 0.01% KNO~3~, 0.01% Mg(NO~3~)~2~-6H~2~O, 0.036% CaCl~2~-2H~2~O, and 13.5% sucrose) as described previously ([@bib39]) at 25°C. Pollen was grown for 1 h before any treatments were applied. For SI treatments, recombinant proteins were produced by cloning the nucleotide sequences specifying the mature peptide of the S~1~, S~3~, and S~8~ alleles of the S gene (pPRS100, pPRS300, and pPRS800) into the expression vector pMS119 as described previously ([@bib7]). Expression and purification of the proteins were performed as described previously ([@bib20]). SI was induced by adding recombinant S proteins (final concentration of 5 μg/ml) to pollen growing in vitro as described previously ([@bib39]). For DNA fragmentation experiments with actin inhibitors, LatB or Jasp (both from Calbiochem) were added to growing pollen tubes at various concentrations. Pollen was grown for a total of 8 h, after which it was fixed in 2% PFA and assayed for DNA fragmentation (see next section). For washout experiments, after short treatments with LatB or Jasp, pollen tubes were washed extensively in GM (six washes of 5 ml for 5 min each). Pollen tubes were resuspended in GM and incubated for the remainder of the 8-h period. Controls were comprised of the addition of DMSO at a final concentration of 0.1% (vol/vol). Caffeine (Sigma-Aldrich) treatments consisted of the addition of the drug to pollen tubes at a final concentration of 3 mM; pollen was incubated for 10 or 60 min before washouts as described above. Controls were comprised of the addition of GM alone. For the SI-Jasp experiments, pollen tubes were subjected to two antagonistic treatments with incompatible S proteins and Jasp. To ascertain a suitable Jasp treatment, washout experiments were conducted. Treatments of 0.5 μM Jasp for 10 and 30 min followed by washouts only stimulated levels of DNA fragmentation between 31.2 ± 2.5 and 33.0 ± 0.4%, respectively. This provided a suitable concentration of Jasp for attempts to counteract the PCD induced by LatB. Consecutive SI-Jasp treatments consisted of the addition of S proteins for 10 min followed by the addition of 0.5 μM Jasp for 20 min. Simultaneous treatments involved the addition of S proteins and Jasp at the same time and incubation for 30 min. Immediately after each treatment, the pollen tubes were washed extensively with GM as described above and were incubated for the remainder of the 8-h period before assaying for DNA fragmentation. Control treatments were comprised of 30 min in 0.1% DMSO or 0.5 μM Jasp. The LatB-Jasp experiments were performed in a similar manner. DNA fragmentation assay ----------------------- Fixed pollen tubes were labeled with a Deadend Fluorometric TUNEL kit (Promega) according to the manufacturer\'s instructions. Pollen tubes were scored for DNA fragmentation (50 tubes per treatment; n = 3) using a fluorescence microscope (T300; Nikon) and a 60× plan-Apo 1.4 NA oil objective (Nikon). Capture and analysis of images was performed at 20°C using a camera (SenSys KAF1400-G2; Photometrics) and an image analysis system (Quips PathVysion; Applied Imaging). Composite images were prepared using Adobe Photoshop 8.0. Caspase assays -------------- To test whether DNA fragmentation was dependent on a caspase-like activity, pollen was grown in the presence of 100 μM DEVD or YVAD (Calbiochem) for 1 h before the addition of the cytoskeletal drugs for 8 h. Samples were then tested for DNA fragmentation using TUNEL. Inhibition of DNA fragmentation by DEVD was taken as evidence for caspase-3--like activity. We also used the fluorogenic caspase-3 substrate Ac-DEVD-AMC (Calbiochem) to establish this caspase-like activity more directly. Pollen tubes were treated with 1 μM LatB and 0.5 μM Jasp or GM for 6 h, and protein extracts were made from them by grinding in extraction buffer (50 mM sodium acetate and 10 mM [l]{.smallcaps}-cysteine, pH 6.0). 10 μg of total protein was incubated with 50 μM Ac-DEVD-AMC at 27°C, and fluorescence was monitored at 460 nm using a time-resolved fluorescence plate reader (FLUOstar OPTIMA; BMG LABTECH). Fluorescence at 480 nm indicated cleavage of the substrate by a DEVDase activity. Relative fluorescence units were expressed as the percent increase relative to the control after 4 h. F-actin imaging --------------- Pollen was grown on GM medium solidified with 1.2% wt/vol agarose, treated with actin inhibitors at various concentrations and different times as described in the figure legends and text, and fixed with 400 μM 3-maleimidobenzoic acid N-hydroxysuccinimide ester (MBS; Pierce Chemical Co.) for 6 min followed by 2% PFA for 40 min. Pollen tubes were washed three times in actin-stabilizing buffer (100 mM Pipes, pH 6.8, 1 mM MgCl~2~, 1 mM CaCl~2~, and 75 mM KCl) and permeabilized with TBS-Tween-DTT (50 mM Tris, pH 7.4, 200 mM NaCl, 0.05% Tween 20, and 5 mM DTT) for 15 min. Except for Jasp-treated pollen tubes, in which the phalloidin-binding site was masked, F-actin was labeled by treatment with 500 nM rhodamine-phalloidin (Invitrogen) for 20 min at RT. All images were collected using a 60× plan-Apo 1.4 NA oil immersion objective (Nikon). Capture and analysis of images was performed at 20°C using a laser-scanning system (Radiance 2000; Bio-Rad Laboratories) and the 543-nm excitation line of a 1.5-mW HeNe laser. Images are optical projections of z series taken at 0.5-μm sections, and each section was the average of three Kalman scans. Images were exported, and composite images were prepared using Adobe Photoshop 8.0. For Jasp-treated pollen, pollen tubes were grown, treated with 0.5 μm Jasp for 10 min, fixed with PFA and MBS, and prepared for immunolocalization. Samples were washed three times in actin-stabilizing buffer and once in MES buffer (5 mM MES, pH 5.0, 5 mM EGTA, and 0.4 M mannitol). Cell walls were digested with 0.1% cellulase and 0.1% macerozyme in MES buffer containing 0.1 mM PMSF for 10 min. Pollen tubes were washed once in MES, washed twice in TBS, permeabilized in 0.1% Triton X-100 in TBS for 10 min, and washed in TBS + 1% BSA. Samples were then incubated with a 1:250 dilution of anti-actin antibody ([@bib14]) overnight at 4°C. Unbound primary antibody was washed out, and the pollen tubes were incubated for 2 h at RT in anti--rabbit FITC antibody (1:200 dilution). All images were collected at 20°C with a 60× plan-Apo 1.4 NA oil objective (Nikon) using a Radiance 2000 laser-scanning system with the 488-nm excitation line of a 50-mW Ar laser. Images are optical projections of z series (0.5-μm sections). Images were exported, and composite images were prepared using Adobe Photoshop 8.0. F-actin quantification ---------------------- Pollen F-actin levels were determined using the modified phalloidin-binding assay described previously ([@bib14]). In brief, LatB-treated pollen tubes were fixed (1.55 M sucrose, 0.1% NP-40, and 600 μM MBS) for 1 h and washed in GM + 0.05% NP-40. Fixed pollen tubes were gradually exchanged into TBS + sucrose (TBSS; 50 mM Tris, pH 7.4, 200 mM NaCl, and 400 mM sucrose) plus 0.05% NP-40 and 2 mM DTT. The TBSS was aspirated from pollen samples, and 50 μl of 2 μM AlexaFluor 488 phalloidin (Invitrogen) in TBSS + 0.05% NP-40 was added to label F-actin at 4°C overnight. After washing, bound phalloidin was extracted in 1 ml methanol overnight at 4°C. The amount of F-actin in the samples was determined by fluorimetry with excitation at 492 nm and emission at 514 nm using a spectrofluorometer (QM-2000-SE; Photon Technology International). Fluorescence values were calculated per 100,000 pollen grains/tube and expressed as the percentage of the relevant control ± SEM. F-actin levels from control samples without LatB treatment were normalized to 100%. Research in the laboratory of V.E. Franklin-Tong is supported by the Biotechnology and Biological Sciences Research Council. Research in the laboratory of C.J. Staiger is supported by a National Research Initiative grant from the U.S. Department of Agriculture (2002-35304-12412) and by an Energy Biosciences Division grant from the U.S. Department of Energy (DE-FG02-04ER15526). [^1]: Correspondence to Vernonica E. Franklin-Tong: <v.e.franklin-tong@bham.ac.uk>
Hair transplant by incisional strip harvesting. The art of hair transplantation has continued to develop, achieving surgical correction with an enhanced aesthetic outcome. We have used incisional harvesting with donor site closure and have found that incisional harvesting allows for much more latitude in choosing slit, strip, micro, mini, or the standard round or square punch technique.
Hypochlorous acid and chloramines increase endothelial permeability: possible involvement of cellular zinc. The migration of neutrophils through the endothelium at sites of inflammation may be facilitated by oxidant-mediated disruption of cellular junctions. The present study examined the effects of noncytotoxic concentrations of the membrane-penetrating neutrophil oxidants hypochlorous acid (HOCI) and monochloramine (NH2Cl), or the membrane-impermeant taurine chloramine (taurine NCl), on cultured bovine aorta endothelial monolayers. HOCl (25 microM) or NH2Cl (10 microM), but not taurine NCl (100 microM), caused a reversible shortening of the cytoskeletal actin microfilaments, cell retraction, and increased permeability within 2 min. These effects were accompanied by an increase in intracellular zinc concentration as well as the oxidation of intracellular glutathione and protein sulfhydryls. The zinc ionophore pyrithione also increased permeability. HOCl or NH2Cl, but not taurine NCl, also rapidly increased microvascular permeability in isolated perfused rat lungs. The data suggest that HOCl and NH2Cl can increase endothelial permeability by causing very rapid cytoskeletal shortening and cell retraction, possibly as a result of the oxidation of intracellular sulfhydryls and mobilization of zinc.
Table of Contents Title Page Dedication Acknowledgements Introduction Chapter 1 - Give It Up Chapter 2 - Carbs: The Truth Chapter 3 - Sugar is the Devil Chapter 4 - The Dead, Rotting, Decomposing Flesh Diet Chapter 5 - The Dairy Disaster Chapter 6 - You Are What You Eat Chapter 7 - The Myths and Lies About Protein Chapter 8 - Pooping Chapter 9 - Have No Faith: Governmental Agencies Don't Give a Shit About Your Health The USDA: It's Not What You Think Safety Last Business First All in a Day's Work Organic or Not? Is Everyone in the FDA on Drugs? You Are Your Only Chance The EPA Makes Us Sick Trust No One Chapter 10 - Don't Be a Pussy Vitamins Chapter 11 - Let's Eat Breakfast Food List Lunch Food List Dinner Food List Acceptable Junk Food, Snacks & Desserts Condiments, Baking Supplies & Miscellaneous Week One Week Two Week Three Week Four Bad or Potentially Bad Ingredients* Scary-Sounding But Actually Harmless Ingredients Chapter 12 - FYI Chapter 13 - Use Your Head Afterword Recommended Reading Sources Consulted Endnotes Copyright Page Dedication _For Tony Robbins and Dr. Wayne Dyer, with much love and appreciation._ _It is because of your work that this book exists._ _And for all the truth-speakers and seekers who have made the world a better place while dramatically influencing our lives: We thank you and honor all that you have done and continue to do in the name of what is right._ _Namastè._ Acknowledgments It is with the utmost gratitude that we thank Lyssie Lakatos, Tammy Lakatos-Shames, Talia Cohen, Laura Dail, Jennifer Kasius, Maria Taffera Lewis, Nancy Armstrong, and Greg Jones for bringing this book to life. We acknowledge the keen eyes of Meri Freedman and Dr. Amy Joy Lanou, and heartfelt thanks to our dream-team: Jon Anderson, Craig Herman, Seta Zink, Peter Costanzo, and everyone at Perseus Books, Running Press and Creative Artists Agency for leading us above and beyond. For your kind and patient help, we sincerely thank Chloe Jo Berman, James Costa, Matt Green, Bruce Friedrich, Holly Sternberg, Mark Gold, Kristina Johnson, Sara Chenoweth, Harold Brown, Ryan Zinn, Michele Simon, Talia Berman, Danielle Simon, Wayne Pacelle, Jay and Wendy Baxter, and Shaun Zaken. We are honored by the generous contributions of C. David Coates, Christine Hoza Farlow, D.C., and Tim VanOrden and cannot thank you enough. # _Rory:_ Kim, my partner in crime, I cannot imagine the existence I'd be leading if we never met. Thank you for changing the course of my life and enlightening me with your glow. You had me at hello. It is with true adoration that I thank Tracy Silverman, who started me on this path, Lauren Silverman, who inspired me to commit to it more fully, Jesse Hildebrandt, for enabling me to do so, and my magical friends who made the journey by my side: Sue Foley, Todd and Lisa Adamek, Nora Ariffin, Emily Ashba, Dave Feeney, Fara Horowitz, Jill Iacuzzo, Jessica Jonas, Margaret Klinger, Denise Kunisch, Lisa Leder, Chris Lucia, Julie Lundberg, Kerri Meyers, Lori Morgen, Luke Orefice, Michelle Pappas, Andrea Pendas, Brian and MC Permenter, Jackie Poper, Randie Rolantz, Christine Santoro, Kim Snowden, Nora Stein, Louie and Christine Tibolla, Susan Weinberg, and all my PR pals who are too numerous to name. To my grandmothers, Florence Freedman and Frances Levine, thank you for your inexhaustible supplies of love and faith. For your endless enthusiasm and loving encouragement, I thank my sister and brother-in-law, Lesley and Tim Bailey. Most of all, my parents, Rick and Meri Freedman—it is with an overflowing heart that I thank you for a lifetime of your unwavering support and love. # _Kim:_ My amazing friend and business partner, Rory, without you none of this would be happening. I thank God every day that we met and shared the same dream. We leapt and the net appeared. Thank you for leaping with me. Keesha Whitehurst Frederickson, I am so glad you are a part of my life. Thank you for all the laughter and love, and for being so special. To all my other friends who honor me with their day-to-day presence, I thank you. A million thanks to my wonderful parents, Richard and Linda Robinson, who believed in me and cheered me on through the hard times and the good times. # To Jeri, Chrissy, Amanda, Melissa, Alex, and Elliot: I love you! And last but not least, my love: my husband, Stephane. There are not enough words in any language to express my love for you. I am so grateful for your never-ending patience, constant faith, pure love, and undying support. I feel so blessed to be traveling through this life with you. Je T'aime. Introduction A re you sick and tired of being fat? Good. If you can't take one more day of self-loathing, you're ready to get skinny. You don't need a degree in biology to get skinny. You don't need to starve yourself to get skinny. You don't need to spend all day at the gym to get skinny. You just need to smarten up and use your head. Really. It is that simple. We have been so brainwashed by fad diets, magazine articles, and advertising that we have forgotten how to think for ourselves. _Skinny Bitch_ delivers the truth about food, so that you can make intelligent and educated decisions for yourself. This knowledge will empower you to become a skinny bitch. This is not a diet. This is a way of life. A way to enjoy food. A way to feel healthy, clean, energized and pure. It's time to reclaim your mind and body. It's time to strut your skinny ass down the street like you're in an episode of _Charlie's Angels_ with some really cool song playing in the background. It's time to prance around in a thong like you rule the world. It's time to get skinny. Chapter 1 Give It Up O kay. Use your head. You need to get healthy if you want to get skinny. The first thing you need to do is give up your gross vices. Don't act surprised! You cannot keep eating the same shit and expect to get skinny. Or smoke. So don't even try some pathetic excuse like, "But if I quit smoking, I'll gain weight." No one wants to hear it. Cigarettes are for losers. They are so 1989 and totally uncool. Not only do they screw up your whole body chemistry, but they also kill your taste buds. It's no wonder you eat shit and garbage. Smoking's out. Give it up. Of course it's easier to socialize after you've had a few drinks. But being a fat pig will hinder you, sober or drunk. And habitual drinking equals fat-pig syndrome. Beer is for frat boys, not skinny bitches. It makes you fat, bloated, and farty. Why do you think when kids go away to college they gain the "freshman fifteen"? Beer, duh. Alcohol isn't any better. It raises the level of hydrochloric acid in your stomach, wreaking havoc on the digestive process. If you suffer from poor digestion, then your food will not pass through your body properly. Hence, bloated fat-pig syndrome. To make matters worse, some alcohol (and non-organic wines) still contains urethane, a cancer-causing chemical. To boot, both beer and alcohol jack up your blood-sugar levels, which is bad for your bod. And don't kid yourself: When you have a hangover, you're bound to eat shit all day long. Trade your booze for organic red wine produced without sulfites. (Sulfites are additives—used in food and wine—to extend shelf life and fight bacteria growth. Asthma and allergic reactions can be triggered by sulfites. Even if wine is organic, that doesn't mean it is produced without sulfites. Read the label; it should say "No Sulfites Added" or "NSA." Frey Vineyards makes organic, sulfite-free wines.) This magical elixir—organic red wine with NSA—is rich in cancer-fighting antioxidants, can reduce risk of stroke, helps thin the blood, and has flavonoids, which lower cholesterol. Yes, organic red wine is good for you. No, you should not drink a bottle by yourself every day. Alcohol abuse can cause infertility, cancer, infectious diseases, cardiovascular disease, shrinking of the cerebral cortex, and alter brain-cell function. If you need help quitting drinking, call the Alcoholics Anonymous World Headquarters at (212) 870-3400 to find an AA meeting near you, or visit www.alcoholics-anonymous.org. Brace yourselves, girls: Soda is liquid Satan. It is the devil. It is garbage. There is nothing in soda that should be put into your body. For starters, soda's high levels of phosphorous can increase calcium loss from the body, as can its sodium and caffeine. [Cousens, _Conscious Eating_ , 475] You know what this means—bone loss, which may lead to osteoporosis. And the last time we checked, sugar, found in soda by the boatload, does not make you skinny! Now don't go patting yourself on the back if you drink diet soda. That stuff is even worse. Aspartame (an ingredient commonly found in diet sodas and other sugar-free foods) has been blamed for a slew of scary maladies, like arthritis, birth defects, fibromyalgia, Alzheimer's, lupus, multiple sclerosis, and diabetes. When methyl alcohol, a component of aspartame, enters your body, it turns into formaldehyde. Formaldehyde is toxic and carcinogenic (cancer-causing). Laboratory scientists use formaldehyde as a disinfectant or preservative. They don't fucking _drink_ it. Perhaps you have a lumpy ass because you are preserving your fat cells with diet soda. The Food and Drug Administration (FDA) has received more complaints about aspartame than any other ingredient to date. Want more bad news? When aspartame is paired with carbs, it causes your brain to slow down its production of serotonin. A healthy level of serotonin is needed to be happy and well balanced. So drinking soda can make you fat, sick, and unhappy. Unless you're from Mars, you've heard about the "eight glasses of water a day" thing. If you're filling up on 16 ounces of liquid Satan at a time, chances are you're not getting your 64 ounces of water a day. Water is vital for keeping your body clean and detoxified. It literally flushes out all the shit and toxins your body stores from your horrendous diet. You might be fat because you don't poop enough. Drinking lots of water can help with the elimination process. If the taste of water bores you, try jazzing up the flavor with a slice of lemon or lime, or, if you're feeling sassy, toss in a strawberry or raspberry. Say goodbye to soda and hello to a sweet ass. "Don't talk to me until I've had my morning coffee." Uhm . . . _pathetic_! Coffee is for pussies. Think about how widely accepted it has become that people _need_ coffee to wake up. You should not _need_ anything to wake up. If you can't wake up without it, it's because you are either addicted to caffeine, sleep deprived, or a generally unhealthy slob. It may seem like the end of the world to give up your daily dose, especially if you rely on Starbucks as a good place to meet men. But it's not heroin, girls, and you'll learn to live without it. Caffeine can cause headaches, digestive problems, irritation of the stomach and bladder, peptic ulcers, diarrhea, constipation, fatigue, anxiety, and depression. It affects every organ system, from the nervous system to the skin. Caffeine raises stress hormone levels, inhibits important enzyme systems that are responsible for cleaning the body, and sensitizes nerve reception sites. One study even links caffeine to an increased susceptibility to diabetes. But don't go grabbing for the decaf. Coffee, whether regular or decaf, is highly acidic. Acidic foods cause your body to produce fat cells, in order to keep the acid away from your organs. (Please, do not link this acid issue to citrus and other fruits. We discuss this in depth later on page 38.) So coffee equals fat cells. P.S. It also makes your breath smell like ass. Furthermore, coffee beans, like other crops, are grown with chemical pesticides. One insecticide, D-D-7, has been banned in the United States, but is still used by other countries from which we import coffee beans. So every single morning, you are starting your day with a dose of poison. Add sugar or other artificial sweeteners, top it off with milk or cream, and you'll be fat forever. If you enjoy an occasional cup of coffee, fine. But if you need it, give it up. A much better way to start the day is with a cup of caffeine-free herbal tea—organic, of course. Decaffeinated green tea is like a wonder drug. Its anti-aging and antibacterial qualities are as renowned as its reputation for fighting cancer, combating allergies, and lowering blood pressure. But don't overdo it or you may be at an increased risk for kidney stones. Go to a coffeehouse, if you must. Just get a decaf organic herbal tea instead of coffee. Miss your caffeine jolt? Get a fresh-squeezed organic juice for an instant jump start. Once you are rid of your caffeine addiction, you will get totally high from fresh-squeezed juice. Junk food will never go away. It becomes more alluring by the minute with laboratory-developed aromas, artificial flavors, chemical food colors, toxic preservatives, and heart-stopping hydrogenated oils. We know these are all impossible to resist, but no one ever got skinny on junk food. Use your head. Candy bars, potato chips, and ice cream taste like heaven, of course. But they will pitch a tent on your hips and camp out all year. Not only are they bogged down with saturated fats, sugars, hydrogenated oils, calories, and cholesterol, but they also contain enough chemical residues to put hair on your chest. Ever heard of butylated hydroxyamisole (BHA) or butylated hydroxytoluene (BHT)? Most people haven't, even though these chemical preservatives are either put in food or into the packaging. The FDA doesn't require companies to divulge the presence of these beauties if they are used in packaging, though they can come into contact with the food you're eating. So your junk food has a shelf life of twenty-two years and will probably outlive your fat, sorry ass. Now before you decide you're so smart because you only buy fat-free snacks, get a hold of yourself. Whenever you see the words "fat-free" or "low-fat," think of the words "chemical shit storm." Read the ingredients. Do you really think sugar or hydrogenated oils or eggs or milk won't make you fat? Sober up, asshole. By the way, sugar, like coffee, creates an acidic environment in your body. You just learned that acidic foods cause your body to produce fat cells. So you do the math: sugar = fat. If you'd drag your cankles to a health food store, you'd find aisle after aisle of "acceptable junk food." Guilt-free garbage that tastes so good, you'll do naked cartwheels around your living room. We are not saying you have to give up junk food to get skinny. You just have to trade your old junk food for new junk food. In Chapter 11, we provide an "acceptable junk food" list that'll make your nipples hard. Are you a pill popper? Do you reach for over-the-counter medicine for every sniffle, sneeze, ache, and pain? Toughen up. Our bodies, when properly cared for, function as perfect machines. Our brains tell us when something is wrong by giving us pain or discomfort. When we pop pills to rid this "dis-ease," we are masking the symptoms without resolving the problem. Every time you take medicine, you interfere with your body's natural ability to heal itself. You are alleviating those intelligent responses that alert you to a problem, and sending false signals to your brain. If you have a headache, you might be tired, dehydrated, or suffering from a minor food allergy. Most likely, your body is having an adverse reaction to the unhealthy crap you're eating. Taking two aspirin is not the answer. If your nose is running, your body is trying to rid itself of something through your snot. But you, drama queen, take cold medicine to stop your booger flow. Now you've gone and fucked up everything. Medicine is made of chemicals. Never mind that the Food and Drug Administration gives meds their stamp of approval. They also allow the use of aspartame. Use your own damn brain. Do you think putting _chemicals_ in your body is good for you? Every medicine comes complete with a list of side effects. That means that taking medicine will make you feel better for the moment, but will fuck up something else in your body. Yeah, getting cramps totally sucks. It's supposed to. Every month you endure cramps (without medication), you are preparing for the physical pain of childbirth. So suck it up. Stop interfering with Mother Nature. (Obviously, if you are on prescribed medication, you need to consult a physician before discontinuing it.) Give up the notion that you can be sedentary and still lose weight. You need to exercise, you lazy shit. Eating properly will dramatically improve your health, body, and all aspects of your life. But you've still gotta move your ass. Anyone with a brain can do the math: When done in conjunction with a good diet, exercise will make you lose weight faster than healthy eating alone. You don't need to spend seven days a week at the gym. In fact, you shouldn't, because too much exercise is bad for you. It can lead to dehydration, arthritis, osteoporosis, and injuries like strains, sprains, and fractures. Over-exercising can also cause low body-fat levels, which can disrupt the menstrual cycle and cause reproductive problems. You want to be a Skinny Bitch, not a scrawny bitch. Twenty minutes of cardiovascular a day, five days a week, is a good starting point. Then, after a couple of weeks, kick it up a notch. Depending on your fitness goals, you can increase your cardiovascular workout or add strength training to your routine. Aim for working out in the morning, if you can. When we exercise, our elevated heart rates and deep breathing cause our "body minds" to enter a fat-burning mode that can last throughout the day. Regardless of what time you work out, you'll soon become addicted to exercising. When we are active enough to break a sweat, our brains release endorphins and feel-good opiates. Exercise burns fat and calories, improves circulation, regulates crapping, defines muscles, builds strength, and detoxifies the body through sweating. Plus, working out tends to keep our junk food cravings and elephant appetites at bay. It's a win-win. Work out. Chapter 2 Carbs: The Truth N ever before has the United States seen such a ridiculous diet trend as the "low-carb" phenomenon. Every restaurant, grocery store, and fast-food chain caters to this utter nonsense. Even soda and beer companies have spent millions developing and marketing low-carb drinks. Everyone has jumped on the bandwagon, hoping to capitalize on the trend, whether it is healthy or not. Not. Carbohydrates are compounds made up of carbon, hydrogen, and oxygen, and they are _vital_ for providing energy for our bodies and brains. Without them, we would be comatose zombies. When we eat food, our bodies turn the carbohydrates into glucose for immediate energy and the rest is stored as glycogen for reserves. Yet all carbs are not created equal. There are two types: simple and complex. Simple carbohydrates suck and are as nutritionally beneficial as toilet paper. They are mostly made up of sugar, which releases too quickly, almost violently, into our bodies, causing "sugar highs" and then "crashes." This tends to leave us feeling hungry, so we eat more. On the other hand, complex carbohydrates are comprised of starch and fiber and release gradually, providing a steady source of energy. They make us feel full and satisfied and are easily broken down to release their energy. Shitty simple carbohydrates include white flour, white pasta (durum semolina), white rice, and white sugar. These are the bad boys that give all carbs a bad reputation. For some asinine reason, food manufacturers decided that we wouldn't buy their products unless they were white and soft. So they took natural grains, like brown rice and whole wheat, and stripped away all their nutrients, vitamins, and minerals to achieve the color and texture change. This refining process totally compromises the nutritional integrity of the food—all for appearances. So companies then add these nutrients back into their refined, milled foods and use terms like "enriched" or "fortified." But there's no use trying to fool with Mother Nature. Our bodies cannot absorb these added-in minerals with the same ease. Tragically, most cereals, pastas, rice, bagels, breads, cookies, muffins, cakes, and pastries have been bastardized in this manner. Pay attention to how your body feels when you eat these foods. Chances are you'll notice moderate to severe mood swings and energy surges and losses. Fear not. There are so many complex carbohydrates (Mother Nature is generous) that you'll never miss the simple shit. Bask in the glory of potatoes, yams, sweet potatoes, barley, corn, brown rice, beans, hummus, lentils, quinoa (a grain, pronounced KEENWA), millet, and pasta made from brown rice, whole wheat, or vegetables. Bionaturae, Ancient Harvest, Eddie's Spaghetti, Lundberg Farms, Westbrae, Pastariso, and DeBoles Organic all carry these "good carb" pastas. Relish the beauty of breads and cookies and muffins made from whole wheat and other whole grains. (Whole grains are any that haven't been bleached, stripped, or refined and still possess all the nutrients from the original grain.) Food For Life has an amazing line of whole and sprouted grain breads, and Pacific Bakery and French Meadow Bakery carry organic breads that aren't too shabby, either. Don't forget the bounty of vegetables and fruits—complex carbs that supply the body with vitamins, minerals, and fiber. Yeah, you heard us—fruit. Eat it. The most irritating thing about the low-carb craze is the resistance to eating fruit. Fruit is, quite possibly, the most perfect food in existence. It is unique in that it barely requires any work to be digested. High in enzymes, it effortlessly passes through the body, supplying carbohydrates, fiber, vitamins, minerals, fatty acids, amino acids, and cancer-fighting tannins and flavonoids. Because it is made up of mostly water, fruit hydrates the body and aids in cleansing, detoxifying, and eliminating. Best-selling _Fit for Life_ authors Harvey and Marilyn Diamond suggested that fruit best serves our bodies when eaten alone because it is so easily and quickly digested. According to them, when we eat fruit with other foods, it cannot pass through our bodies as quickly. So it rots and ferments in our stomachs. This can cause burping, bloating, and heartburn. To combat this, the Diamonds recommend eating fruit on an empty stomach, first meal of the day, and waiting thirty minutes before eating anything else. (We know this will be tough for some people, and it's okay if you aren't ready to tackle this challenge yet. It's just something to try and see if it feels right for you.) So shout it from the rooftops until every one of your dumb-ass, misinformed friends hears: YOU CAN EAT BREAD AND FRUIT! Chapter 3 Sugar is the Devil W e all know how difficult it is to stay away from sugar. But if you don't exorcise this demon from your diet, you will never be a skinny bitch. Take a look around your kitchen and become aware of all the places the devil is lurking. Probably in places you wouldn't ever expect to find "him." Read the ingredients of your breakfast cereals, breads, crackers, junk foods, everything. Sugar is like crack, and food manufacturers know that if they add it to their products, you'll keep coming back for more. What is this evil entity? In its simplest form, it is the juice from a sugar cane plant. A plant—that seems benign, right? And it is, in moderation, ingested in its raw, simplest form. But all the enzymes, fiber, vitamins, and minerals are destroyed during the refining process. First, the cane is pressed to extract the juice. Then, the juice is boiled so that it will thicken and crystallize. Next, it is centrifuged, or spun, to remove the syrup. After that, the sugar is washed and filtered to remove any nonsugar materials and to decolorize it. (By the way, sugar filters are commonly made of charred animal bones. Nasty.) Finally, the sugar is dried and packaged. So you see, refined sugar has no nutritional value. And it's usually in foods that contain gobs of fat, lots of useless calories, and loads of cholesterol. So, you become addicted to foods (because they contain sugar) that have a large amount of fat, saturated fat, hydrogenated oils, and calories. Refined sugar, a simple carbohydrate, has been linked to hypoglycemia, yeast overgrowth (check your undies), a weakened immune system, hyperactivity, attention deficit disorder, enlargement of the liver and kidneys, increase of uric acid in the blood, mental and emotional disorders, dental cavities, and an imbalance of neurotransmitters in the brain. In addition, refined sugars make you _fat_. Excess amounts are stored in the liver as glycogen. But when the liver is too full, the excess amounts are returned to the bloodstream as fatty acids. Guess where those end up? Hips, stomach, thighs, and ass. The sugar industry is big business in America. The United States is the largest supplier of sugar-laden foods in the world. It's not enough to poison our own citizens. We have to fuck up the rest of the world, too, for a dime. High fructose corn syrup is another badass that finds its way into tons of foods. Manufacturers love its versatility and put it in nearly everything: juice, soda, beer, yogurt, energy bars, cookies, candies, breads, even frozen goods. High fructose corn syrup is processed more than sugar and is even sweeter. But it's a friend of the farmer because it's so cheap to produce. Like refined sugar, it has a negative, dramatic effect on our blood-sugar levels. According to studies conducted by the _American Journal of Clinical Nutrition,_ diabetes and obesity are directly linked to eating refined sugar and high fructose corn syrup. We aren't telling you to give up cookies for the rest of your lives; we certainly don't want to start a riot. We're simply suggesting that you substitute natural, healthier alternatives for refined sugar. At the top of the list is agave nectar or syrup. This high-nutrient sweetener can actually be beneficial to your health. It doesn't contain any processing chemicals, and the raw version (completely un-processed) contains vitamins and minerals. It can be used in place of sugar in any product or recipe. Stevia, another winner, is derived from a plant found in Paraguay. The Japanese have been using this wonder sweetener for decades, South Americans for centuries. In fact, it is used by hundreds of millions of people around the world to balance blood-sugar levels, reduce cravings for sweets, and aid in digestion. Additionally, it is known for its antimicrobial properties (it inhibits the growth of bacteria). Unfortunately, however, it is the most unrecognized sweetener in the United States. This natural, herbal sweetener contains no calories, has no glycemic index (meaning it won't alter blood sugar), and is even safe for diabetics. But for reasons unknown to intelligent species everywhere, the Food and Drug Administration won't approve Stevia for use in food products. Maybe they are sleeping with the sugar industry. Other good substitutes for refined sugar include evaporated cane juice, Sucanat, brown rice syrup, barley malt syrup, Rapadura sugar, Turbinado sugar, raw sugar, beet sugar, date sugar, maple syrup, molasses, and blackstrap molasses. (Some companies add lard to maple syrup or molasses to reduce foaming, so be sure you are buying 100 percent pure, organic products.) Don't shit and piss yourselves, but all of these natural sweeteners possess one or more of the following health benefits: enzymes, calcium, iron, potassium, protein, the B vitamins, magnesium, chromium, fiber, and folic acid. Some even contain complex carbohydrates. We're not saying you should eat naturally sweetened cupcakes three meals a day. We're just saying that you _can_ have your cake and eat it. Just use your head regarding the amount of sweets you consume. A drum roll, please, for a few of our favorite sweets: Uncle Eddie's vegan cookies, Tropical Source or Terra Nostra chocolate bars, Oreo knock-offs by Back to Nature or Country Choice, organic Fig Newmans, and all the cookies by the Sun Flour Baking Co. and the Alternative Baking Co. Now that you've heard the good news about natural sweeteners, it's time to give up the all the bad ones. Obviously, refined sugar is bad for you, as is high fructose corn syrup. And in case you had your head up your ass during Chapter 1, STOP EATING AND DRINKING PRODUCTS THAT CONTAIN ASPARTAME! This includes diet sodas and sugar-free foods that have NutraSweet or Equal. When aspartame was put before the FDA for approval, it was denied _eight_ times. G.D. Searle, founder of aspartame, tried to get FDA approval in 1973. Clearly, he wasn't bothered by reports from neuroscientist Dr. John Olney and researcher Ann Reynolds (hired by Searle himself) that aspartame was dangerous. Dr. Martha Freeman, a scientist from the FDA Division of Metabolic and Endocrine Drug Products, declared, "The information submitted for review is inadequate to permit a scientific evaluation of clinical safety." Freeman recommended that until the safety of aspartame was proven, marketing the product should not be permitted. Alas, her recommendations were ignored. Somehow, in 1974, Searle got approval to use aspartame in dry foods. However, it wasn't smooth sailing from there. In 1975, the FDA put together a task force to review Searle's testing methods. Task force team leader Phillip Brodsky said he "had never seen anything as bad as Searle's testing" and called test results "manipulated." Before aspartame actually made it into dry foods, Olney and attorney and consumer advocate Jim Turner filed objections against the approval. In 1977, the FDA asked the U.S. attorney's office to start grand jury proceedings against Searle for "knowingly misrepresenting findings and concealing material facts and making false statements in aspartame safety tests." Shortly after, the U.S. attorney leading the investigation against Searle was offered a job by the law firm that was representing Searle. Later that same year, he resigned as U.S. attorney and withdrew from the case, delaying the grand jury's investigation. This caused the statute of limitations on the charges to run out, and the investigation was dropped. _And_ he accepted the job with Searle's law firm. Stunning. In 1980, a review by the Public Board of Inquiry set up by the FDA determined that aspartame should not be approved. The board said it had "not been presented with proof of reasonable certainty that aspartame is safe for use as a food additive." In 1981, new FDA Commissioner Arthur Hull Hayes was appointed. Despite the fact that three out of six scientists advised against approval, Hayes decided to overrule the scientific review panel and allow aspartame into limited dry goods. In 1983, he got it approved for beverages, even though the National Soft Drink Association urged the FDA to delay approval until further testing could be done. That same year, Hayes left the FDA amid charges of impropriety. The Internal Department of Health and Human Services was investigating Hayes for accepting gratuities from FDA-regulated companies. He went to work as a consultant for Searle's public relations firm. Interesting. The FDA finally urged Congress to prosecute Searle for giving the government false or incomplete test results on aspartame. However, the two government attorneys assigned to the case decided not to prosecute. Later, they went to work for the law firm that represented Searle. Fascinating. Despite recognizing ninety-two different symptoms that result from ingesting aspartame, the FDA approved it for use, without restriction, in 1996. Brilliant. So many people have been sickened from this shit that there are aspartame victim support groups. Some of the ninety-two aspartame side effects listed by the FDA include memory loss, nerve cell damage, migraines, reproductive disorders, mental confusion, brain lesions, blindness, joint pain, Alzheimer's, bloating, nervous system disorders, hair loss, food cravings, and weight gain. Aspartame is a $1 billion industry. The National Justice League has filed a series of lawsuits against food companies using aspartame, claiming they are poisoning the public. In September 2004, a class action lawsuit was filed for $350 million against NutraSweet and the American Diabetics Association. Secretary of Defense Donald Rumsfeld is named in the suit for using political muscle to get aspartame approved by the FDA. NutraSweet and Equal contain aspartame. When ingested, one of aspartame's ingredients, methyl alcohol, converts into formaldehyde, a deadly neurotoxin. In addition to aspartame, Equal contains the amino acid phenylalanine. Phenylalanine occurs naturally in the brain. But high levels can increase the chance of seizures and lead to depression and schizophrenia. There is no lesser of the two evils. NutraSweet and Equal are both evil. Sweet & Low is no saint, either. It is an artificial sweetener that contains saccharin, a coal-tar compound. Stay away. Because we're having so much fun, let's bash the shit out of Splenda, one of the newer sweeteners. Splenda is made by chlorinating sugar, changing its molecular structure. The finished product is called sucralose. The makers of this poison tout its lack of calories and claim it's safe for diabetics. The FDA calls sucralose 98 percent pure. The other 2 percent contains small amounts of heavy metals, methanol, and arsenic. Well, gee, at least it doesn't have calories. So what if it has a little arsenic? Sucralose has been found to cause diarrhea; organ, genetic, immune system, and reproductive damage; swelling of the liver and kidneys; and a decrease in fetal body weight. What a splendid product! According to Dr. Joseph Mercola in Consumer Research magazine's article "The Potential Dangers of Sucralose," "There is no clear-cut evidence that sugar substitutes are useful in weight reduction. On the contrary, there is some evidence that these substances may stimulate appetite." Not only have multiple class action lawsuits been filed, but even the president of the National Sugar Association and the manufacturer of Equal are up in arms about Splenda. They each filed suit, claiming that Splenda manufacturers are misleading consumers into thinking the product is natural when it is "a highly processed chemical compound." Don't think that the giants behind artificial sweeteners and the sugar industry suddenly started caring about public health. Splenda's clever marketing is just totally screwing up their sales. But even executive director for the Center for Science in the Public Interest, Dr. Michael F. Jacobson, who normally criticizes The National Sugar Association, had to agree: "Advertising and labeling, whether for products that are healthful or unhealthful, should be truthful and not misleading." Clearly, artificial sweeteners and refined sugars are bad for many reasons. Here's one more. We have a delicate balancing act occurring in our bodies at all times—pH balance. Basically, everything we eat has its own pH balance. When food is digested, it leaves an acid or alkaline "ash" in the body, depending on the food's mineral content. Surprise, surprise: Artificial sweeteners are highly acid forming. (Coffee, excessive protein, meat, pasteurized dairy, refined sugars, and fatty foods are, too.) When our bodies get too acidic, we are much more prone to illness. Sometimes, we don't even know we're sick until it's too late. But we can notice mild maladies, like skin problems, allergies, headaches, colds, or yeast infections. Or, we can experience major trauma—severe damage to our thyroid gland, liver, and adrenal glands. If our pH balance becomes too acidic, our bodies will react to protect themselves. To neutralize the acid, they will take alkalizing minerals from our reserves. If our reserves are low, the body will withdraw minerals from our bones and muscles. If that doesn't scare you, consider this: It is commonly believed that cancer cells thrive in acid environments. Now, logically, you would think that citrus fruits are acidic, but actually, when they enter the body, they are alkalizing. We know this goes against the "use your own head" idea because they seem like they'd be acidic. But they contain potassium and calcium, which are alkalizing minerals. They also have a high percentage of alkaline salts. Nearly all fruits, vegetables, and legumes are alkaline when they enter the body. Other alkalizing foods are sea vegetables, miso, soybeans, and tofu. Fruit, good. Natural sweeteners, good. Refined sugars, bad. Artificial sweeteners, bad. Any questions? Chapter 4 The Dead, Rotting, Decomposing Flesh Diet T he Atkins diet. Hmm. Eat the flesh of dead cows, dead pigs, and dead chickens. Avoid fresh fruit. You are a total moron if you think the Atkins diet will make you thin. Or, you are a gluttonous pig who wants to believe you can eat cheeseburgers all day long and lose weight. Perhaps you weren't listening the first time: You need to get healthy if you want to be skinny! Eating carcasses all day while avoiding fruit is a recipe for disaster. Of course, if you stop eating refined carbohydrates, you will lose weight. That's the part of the Atkins Diet that actually works. However, most of the weight you lose is water weight. You see, when our bodies metabolize protein (found in high amounts in meat and dairy), nitrogen waste is released in the form of urea. Urea is toxic and must be passed out of the body through urine. So the high-protein diet isn't ridding your body of fat. It's just serving as a diuretic—making you pee more to flush out the toxic urea. But whether you lose this piss weight initially is inconsequential. You will be a fat, unhealthy, bloated pig if you live this way. Trendy diets like Atkins become popular for one reason: They hide behind scientific jargon that _seems_ to make sense and allow you to eat unhealthy, fattening foods as long as you avoid carbs. You believe in these diets because you want to. Most Americans eat twice as much protein as necessary, which has sent obesity, heart disease, and cancer rates soaring over the past fifty years. When you eat large amounts of animal protein and saturated fats and do not eat whole grains, vegetables, and fresh fruits, there is no fiber to bind all of the toxins and fat together to be eliminated from your body. You will eventually do an incredible amount of harm to yourself. Your poor kidneys are in serious jeopardy of developing stones, aging prematurely, and failing altogether. They must work twice as hard to break down protein and remove waste. By the time your blood shows the effects, it will be too late to reverse the damage. Diabetics are in even worse trouble with a high-protein diet because they are already at a higher risk of kidney disease to begin with. In a study involving 1,500 patients with diabetes, most had lost more than half of their kidney function because of a high intake of animal protein. Don't care about your kidneys and just want to lose weight? The American Cancer Society conducted a study over a ten-year period with nearly 80,000 people trying to lose weight. Participants who ate meat three times a week or more gained substantially more weight than participants who avoided meat and consumed more vegetables. Studies published in _The Journal of Clinical Nutrition and The New England Journal of Medicine_ stated that meat eaters are much more likely to be overweight than vegetarians. Before you start spouting off information you've been brainwashed with about evolution and the food chain, read on. Yes, humans have a high level of intelligence. Yes, we created weapons for hunting and fire for cooking. Yes, we found a way to mass-produce animals for consumption. However, if you study animals in the wild, you will note that they do not rely on anything other than their natural hunting ability, speed, strength, claws, teeth, and jaws. They have no tools or weapons. Now look at yourself. Look at your flimsy fingernails in comparison to an eagle's talons. Look at your flat, blunt teeth compared to a lion's fangs. Compare your speed and agility to that of a tiger. Compare the strength of your jaw to a wolf's. Imagine yourself trying to run after an animal, catch it, and kill it using your bare hands, fingernails, teeth, and jaws. Not only would you look ridiculous, but you'd probably get your ass kicked, too. And even if you were successful, envision yourself eating the kill without the aid of an oven and silverware. Yes, the human brain allows us to stay removed from the process of hunting. But does this mean we are "evolved" and "intelligent" and should be eating animal flesh just because we can? Man's "intelligence" also created alcohol, cigarettes, and drugs. Should we drink, smoke, and use just because we can? Many meat eaters credit eating meat for our evolution from cavemen into what we are now. Even if this were the case and eating meat did help us to evolve, look at what we evolved _from_. We looked like friggin' apes and had massive heads, strong jaws, and brute strength. Maybe back then we were supposed to eat meat. But the last time we checked, we aren't cavemen anymore. The second we put food in our mouths, the digestion process begins, thanks to our saliva. Guess what? Our alkaline saliva is not meant to break down animal flesh; carnivores have acid saliva, perfectly designed for the task. And hydrochloric acid, essential for digesting carcass, is secreted in very small amounts in our stomachs. However, the stomachs of carnivores have ten times more hydrochloric acid than ours. Our enzymes, digestive tracts, and organs are all different from those found in carnivores. Like it or not, our kidneys, colon, and liver are ill-equipped to process animal flesh. Compared to carnivores, our intestines are very long, so food that doesn't get adequately processed becomes clogged in our intestines. Animals quickly pass food through their digestive systems, but we have food rotting, decomposing, and fermenting in our intestinal tracts and colons, hence the need for colonics (aka: enemas). You don't see many tigers getting colonics, do you? You do see them napping, though. Even though their bodies are designed to digest meat, animals generally sleep all day while doing so because it is such a taxing process. Genetically and structurally, we are designed to thrive on plant foods. Whether it is "lean meat" or a "skinless chicken breast," animal fat is still animal fat. Don't be fooled by terms coined by the meat industry. Your body can't handle animal fat, so it settles like lumpy shit all over your ass, thighs, sides, arms, and stomach. And then there are the gross, stomach-turning realities of the meat-production industry. Of the ten billion land animals slaughtered each year in America for human consumption, nearly all of them come from factory farms. Factory farms that raise cattle, pigs, chickens, egg-laying hens, veal calves, or dairy cows have an enormous amount of animals in a very small space. There are no vast meadows or lush, green pastures. In the case of chickens and egg-laying hens, the animals are confined inside buildings, where they are literally packed in on top of each other. Egg-laying hens are crammed into cages so small, they are unable to open their wings, and their feet and flesh get mangled around the wire mesh. This overcrowded, stressful environment causes chickens to peck at each other, so the ends of their beaks are seared off their faces using a hot knife. Pigs and cows are imprisoned in stalls so small, they are unable to turn around or lie down comfortably. Cattle are subject to third-degree branding burns and having their testicles and horns ripped out. Pigs also suffer from branding and castration, in addition to the mutilation of their ears, tails, and teeth. They all live in the filth of their own urine, feces, and vomit with infected, festering sores and wounds. To keep animals alive in these unsanitary conditions, farmers must give them regular doses of antibiotics. Half of all the antibiotics made in the United States each year are administered to farm animals, causing antibiotic resistance in the humans who eat them. A study at the University of California-Berkeley linked eating beef to urinary tract infections (UTIs) in women. It just so happens that the most common infectious disease in women is UTIs. You do the math. For shits and giggles, we've compiled a partial list of what's in meat, poultry, seafood, and dairy: benzene hexachloride (BHC), chlordane, dichlorodiphenyltrichloroethane (DDT), dieldrin, dioxin, heptachlor, hexachlorobenzene (HCB), and lindane. Perhaps that's why eating "meat" has been linked to obesity; cancer; liver, kidney, lung, and reproductive disorders; birth defects; miscarriages; and nervous system disorders. American farmers started using chemical pesticides in the late 1800s and were initially thrilled with the results. However, it was eventually noticed that pesticides were killing those who were most exposed to them: farmers, field workers, and animals. In 1972, the Environmental Protection Agency banned DDT. But the pesticides that followed were even worse. BHC is 19 times more carcinogenic than DDT, chlordane 4 times more, dieldrin 47 to 85 times more, HCB 23 times more, and heptachlor 15 to 30 times more. By the late 1980s, of the 450 endangered animal species, more than half were threatened with extinction. The government finally called for a ban on the production and use of other pesticides. But this didn't stop these pesticides from reaching our food supply. Companies were allowed to use up their enormous stockpiles of these pesticides by selling them to countries outside of America. (Apparently, it was acceptable to poison people and animals as long as they weren't American.) These countries used the pesticides on their crops, which were then imported into the United States. Brilliant, huh? And, banned or not, once they have entered the soil or water, pesticides can still poison for decades. One widely used herbicide, glufosinate, whose residues have been found in U.S. waters and food supplies, causes hormonal and brain damage. In his book, _Diet for a Poisoned Planet,_ David Steinman reports that of all the toxic chemicals found in food, 95 to 99 percent come from meat, fish, dairy, and eggs. He also reveals that many of the tests performed don't even detect many chemicals and pesticides. The Food and Drug Administration's own Total Diet Study found that bacon had 48 different pesticide residues, bologna and other luncheon meats had 102 different industrial pollutants and pesticides, fast food hamburgers had 113 residues, hot dogs had 123, and ground beef had 82 industrial chemical and pesticide residues, just to name a few. In comparison, meat contains 14 times more pesticides than plant foods, and dairy has 5 times more pesticides than plant foods. The United States alone uses _one billion pounds_ of pesticides every year on our food. That, our pathetic contamination sampling process, and our use of growth hormones has caused the European Economic Community to reject our meat exportations on numerous occasions. Many animals are even given arsenic-laced drugs. Arsenic! Chemical pesticides are often sprayed directly onto the skin of animals to ward off parasites, insects, rodents, and fungi. In addition, these animals are given food treated with pesticides. On factory farms, bigger is better. More meat, milk, and eggs mean more money for the farmers. So to grow them larger or have them produce more, animals are given steroids and growth hormones. But what is happening to the people who eat these fattened animals? Young girls are experiencing an early onset of puberty at epidemic proportions. Many scientists attribute this to all of the hormones in chicken, meat, and milk that are forced upon children. Basically, every time you consume factory-farmed chicken, beef, veal, pork, eggs, or dairy, you are eating antibiotics, pesticides, steroids, and hormones. This is worth repeating: _Every time you consume factory-farmed chicken, beef, veal, pork, eggs, or dairy, you are eating antibiotics, pesticides, steroids, and hormones._ Now you might be thinking, "Who cares about all this pesticide-cancer shit? I just want to get skinny!" Ever been on The Pill and gained weight? Ever gained weight from having fertility treatments? Well, eating animals that are given hormones has the same effect as if you were taking these directly. According to Dr. Paula Baillie-Hamilton, author of _The Body Restoration Plan,_ antibiotics alone can account for weight gain in animals. She also states that the toxic chemicals used in food production are fattening. Whether it's the pesticides used for growing crops or the chemicals given to animals to fatten them up, they alter the body's metabolism in a way that causes weight gain. Having studied animals and humans, she discovered that low doses of toxic chemicals increased appetite, slowed metabolism, decreased ability to burn stored fat, and reduced ability to exercise. The FDA lists approximately 1,700 drugs approved for use in animal feed. Of these approved drugs, approximately 300 include "weight gain" in their description. However, in their book _Animal Factories,_ Jim Mason and Peter Singer disclose an estimate of 20,000 to 30,000 different drugs actually being used. We constantly hear the snobby declaration, "I don't eat any red meat. I just eat chicken." Well now you know: Chicken is just as bad for you as cow or pig. In fact, it might even be worse. According to the American _Journal of Epidemiology,_ eating chicken (and fish) is linked to colon cancer. Researchers examined the eating habits of 32,000 men and women over a six-year period and then monitored emerging cancer cases for the next six years. "Among participants who generally avoided red meat but who ate white meat less than once per week, colon cancer risk was 55 percent higher than for those who avoided both kinds of meat. Those who had white meat at least once per week had more than three-fold higher colon cancer risk." Researchers at the National Cancer Institute found grilled chicken to have high levels of heterocyclic amines, carcinogens that are formed when animal proteins are heated. With 480 nanograms of heterocyclic amines per gram, grilled chicken registered 15 times higher than beef. Do not be lulled into a false sense of security that our government keeps food safe. News of the avian influenza epidemic came and went, but this disease is very real and can run rampant in poultry flocks. And according to a survey by the National Research Council, one chicken processing plant had 90 percent of its poultry contaminated with salmonellosis. Ninety fucking percent! Nasty. Unfortunately, our waters aren't any better than our land. Yes, some fish contain essential fatty acids and vitamins, minerals, and protein. But you can easily get all these nutrients from flaxseeds; pumpkin, sesame, and sunflower seeds; nuts; soybeans; fruits; vegetables; leafy greens; soy products; and whole grains. Fish and other seafood contain high levels of contaminants from industrial and environmental pollutants, waste products, and pesticide residues from farms. Also present in fish and seafood are high levels of mercury and PCBs, which are well absorbed by the body. Other notables are BHC, chlordane, DDT, dieldrin, heptachlor, and dioxin. These chemicals can cause neuro-toxicity, which impairs a person's mental state and ability. The human body contains acetylcholine, a naturally occurring chemical that helps impulses pass from nerve to nerve. Once the impulse is passed, the chemical is no longer needed and is actually harmful if it remains. So our bodies produce an enzyme, cholinesterase, which rids us of the unwanted acetylcholine. Pesticides inhibit our ability to produce cholinesterase, which causes a buildup of the now-dangerous acetycholine. Mercury, a suspected carcinogen, can alter immune function, raise blood pressure, cause blindness or paralysis, increase the chance of cardiac mortality, and is known to reduce fertility and virility. It can also inflict permanent brain damage on fetuses, infants, and children. Appetizing, huh? Have some mercury poisoning with your ahi tuna. How about some trichinosis with your pork? Don't forget a side of salmonella with your eggs or chicken. We certainly don't want to leave out an order of mad cow disease. Think about what you've been eating. What we call salmon, hamburger, steak, chicken, bacon, sausage, ham, roast beef, salami, bologna, turkey, hot dog, and duck are actually decomposing, rotting animal carcasses. _Bon appétit!_ Closing your eyes to the problem will not make it go away. You don't want to see it, but you'll _eat_ it? So, yeah, if you want to get skinny, you've got to be a vegetarian—someone who doesn't eat dead animals or seafood. Quit whining. We weren't raised by hippie-crunchy-granola parents on vegetarian communes. Growing up, we both ate meat all day, every day. We scoffed at tofu and spit on vegetables. Really. Kim's addictions included such delicacies as corned beef hash, canned Vienna sausages, and daily Big Macs. Every single day in 1992, Rory ate a ham, egg, and cheese sandwich for breakfast, followed by a bacon double cheeseburger, fries, and a soda for lunch. Dinner was always a dead chicken, fish, cow, or pig. Now granted, we didn't give up meat just to get skinny. We both became vegetarians after learning about the treatment of farm animals. But we each noticed big changes in our minds, attitudes, health, moods, and asses when we gave up carcass. So before you say, "I could never give up meat," realize that nearly every single vegetarian on the planet said those same words. Then shut the fuck up, look at an inspirational picture of a skinny bitch, and clean out your freezer. There are a ton of awesome, soy-based fake meat products on the market, which are great for transitioning away from meat. Not only do they taste great, but soy has been lauded for lowering cholesterol, protecting against cancer, reducing the risk of heart attacks, and helping the body to better utilize calcium. Phytoestro-gens, found in soy, help protect women from breast cancer and can alleviate menopausal symptoms. However, there are opponents to soy, who claim that it can negatively impact the thyroid, cause mineral deficiencies, and raise the risk of breast cancer. But according to health expert Dr. Andrew Weil, "There is still much to be learned about soy, but the majority of research so far has shown that it's a safe and nutritious food when eaten in reasonable amounts—about one or two daily servings." We encourage you to think for yourself and make your own decision. If you decide to eat soy products that imitate meat products, know that these foods may not taste exactly like the real thing. But once you get rid of your meat addiction, you'll be satisfied with the substitutes. You just need to spend a few weeks (and dollars) experimenting until you find the ones you like. Veggie burgers exist by the dozen. Health Is Wealth makes fake buffalo wings that taste so good, your pubes will fall out. Gardenburger's Flame-Grilled Chik'n is so amazing, you might have to kill yourself. Lightlife has a kick-ass line of "cold cuts" and fabulous "bacon." One amazing website is _www.vegieworld.com_. It is an Asian mail order company that not only sells fake chicken and meat, but has fake seafood, too. We list lots of meatless wonders in Chapter 11. But remember, getting skinny means using your head. You must read all the ingredients and make sure there are _no_ animal products in anything you buy. Gardein is a great brand that is animal-free and tastes incredible. Chapter 5 The Dairy Disaster G o suck your mother's tits. Go on. Suck your mother's tits. You think this is ridiculous? It is. Get ready to use your head. When a woman gives birth, her body produces milk and she nurses her child. Breast milk can grow an 8-pound newborn into a 24-pound toddler. Sounds pretty fattening, huh? It is. By design, it is intended to allow for the biggest growth spurt of a person's entire life. Breast milk alone can accommodate for a 300 percent weight gain in a twelve-month period. When her child is anywhere from 12 to 24 months old, a mother stops breast feeding. Her milk dries up. The child will never drink breast milk ever again. Cows, like all mammals, are much the same. Their bodies produce milk only when they give birth. Contrary to popular belief, they do not need to be milked—ever. Their udders, like women's breasts, exist even when there is no milk in them. There is one major difference, however. Cows' milk, by design, grows a 90-pound calf into a 2,000-pound cow over the course of two years. It allows calves to double their birth weight in forty-seven days and leaves their four stomachs feeling full. Sounds even more fattening than human milk, right? It is. It should be. Cows are bigger than humans. And the inner workings of their bodies are completely different than ours, which they should be. They are cows. We are humans. Duh. Mammals need the enzyme lactase to digest lactose (the sugar found in dairy). However, between the ages of 18 months and 4 years, we lose 90 to 95 percent of this enzyme. The undigested lactose and the acidic nature of pasteurized milk encourage the growth of bacteria in our intestines. All this contributes to a greater risk of cancer because cancer cells thrive in acidic conditions. Got mucus? Dairy products produce mucus, and often, the body will develop a cold or "allergies" to fight the dairy invasion. Mother Nature is no fool. All species, including ours, have just what we need to get by. She did not intend for grown-ups to suck their mothers' tits. We don't need our mothers' milk as adults, just like grown cows don't need their mothers' milk anymore. We are the only species on the planet that drinks milk as adults. We are also the only species on the planet that drinks the milk of another species. We could be putting gorilla milk on our cereal or having zebra milk and cookies. Why cows' milk? Using the animal that produces the largest quantity of milk but is more easily housed than an elephant means more money for farmers. It has nothing to do with health or nutrition. Again, it all comes back to money. The dairy industry is a multibillion-dollar industry based on brilliant marketing and the addictive taste of milk, butter, and cheese. It has convinced most doctors, consumers, and government agencies that we _need_ cows' milk. We have been told our whole lives, "You need milk to grow. Without milk, your bones will break. If you don't drink milk, you'll get osteoporosis. You need the calcium." _Bullshit_. Researchers at Harvard, Yale, Penn State, and the National Institutes of Health have studied the effects of dairy intake on bones. Not one of these studies found dairy to be a deterrent to osteoporosis. On the contrary, a study funded by the National Dairy Council itself revealed that the high protein content of dairy actually leaches calcium from the body. After looking at thirty-four published studies in sixteen countries, researchers at Yale University found that the countries with the highest rates of osteoporosis—including the United States, Sweden, and Finland—were those in which people consumed the most meat, milk, and other animal foods. Another study showed that though 40 million American women have osteoporosis, only 250,000 African women have bone disease. In fact, of the forty tribes in Kenya and Tanzania, only one—the Maasai—has members suffering from osteoporosis. The Maasai, as it happens, are a cattle-owning, milk-drinking tribe. Dairy products have been linked to a host of other problems, too, including acne, anemia, anxiety, arthritis, attention deficit disorder, attention deficit hyperactivity disorder, fibromyalgia, headaches, heartburn, indigestion, irritable bowel syndrome, joint pain, osteoporosis, poor immune function, allergies, ear infections, colic, obesity, heart disease, diabetes, autism, Crohn's disease, breast and prostate cancers, and ovarian cancer. Harvey and Marilyn Diamond, authors of best-selling follow-up _Fit For Life II,_ clearly state, "DAIRY PRODUCTS ARE DISEASE-PRODUCING. They're harmful. They _cause_ suffering. They're the perfect thing to eat if you want to be sick and have a diseased body. The dietitians and nutritionists who are mouthpieces and cheerleaders for the dairy industry, telling you that dairy products are a good food, should hide their heads in shame—not only for leading the innocent to believe that dairy products are actually valuable, but also for failing to keep abreast of the field about which they are _supposed_ to know something." Yes, we are saying it is common knowledge in the medical research field that dairy is bad for you. Yes, we are saying that executives in the dairy industry are well aware of this fact but make claims that milk "does a body good." How do they get away with this? Easily. They spend hundreds of millions of dollars every year to market their products. And average consumers don't spend their time perusing medical journals, but they do read magazines and watch television. What about medical doctors? Why do they believe that milk is beneficial? It is a sad fact that in this country, most doctors know almost nothing about nutrition. According to a Senate investigation, doctors receive _less than three hours_ of nutritional training in medical school. They have been duped like the rest of us. Let's pretend for a moment that cows' milk is healthy for humans. Even if it were, by the time factory farms were done with it, it wouldn't be. Dioxin, one of the most toxic substances in the world, is often found in dairy products. And remember, for factory farms, higher production means bigger profits. When you consume dairy products, you are ingesting the same antibiotics, pesticides, steroids, and hormones you would if you ate meat directly. Cows are injected with bovine growth hormone. Their udders, under normal conditions, would supply about ten pounds of milk a day. Greedy farmers have their cows producing up to a hundred pounds of milk a day! There is no gentle farmer milking the cow with a bucket between his feet. Cows are milked by machine; metal clamps are attached to the cows' sensitive udders. The udders become sore and infected. Pus forms. But the machines keep on milking, sucking the dead white blood cells into the milk. How freaking gross is that? To get rid of all the bacteria and other shit, milk must be pasteurized. But pasteurization destroys beneficial enzymes and makes calcium less available without even killing all the viruses or bacteria. Hell, even radioactive particles are found in milk But don't the government and U.S. Department of Agriculture protect us from all this? Hell no. Sickeningly high levels of pesticides found in dairy meet government standards. Records from the Food and Drug Administration show that "virtually 100% of the cheese products produced and sold in the U.S. has detectable pesticide residues." Milk is not a reliable source of minerals. You get much higher levels of manganese, chromium, selenium, and magnesium from fruits and vegetables. Fruits and veggies are also high in boron, which helps lessen the loss of calcium through urine. Consuming high amounts of dairy blocks iron absorption, contributing to iron deficiency. So do you need calcium by the trough? Nope. A simple way to get adequate calcium is by including the following foods in your diet: fortified grains, kale, collard greens, mustard greens, cabbage, kelp, seaweed, watercress, chickpeas, broccoli, red beans, soybeans, tofu, seeds (sesame seeds rate among the highest), and raw nuts. It is just that simple. But don't be looking to pop a calcium pill as a quick fix. Research shows that supplements do not make a significant difference in preventing or treating osteoporosis. Good news: Fifteen minutes of direct sunlight every day aides in Vitamin D absorption, which means stronger bones. How about eggs, you ask? When a woman is pregnant and she drinks alcohol or does drugs, it affects her unborn child, right? Right. Well, it is the same with chickens and their unhatched eggs. When you eat eggs, you are ingesting all the same hormones, pesticides, chemicals, and steroids as if you were eating the chicken directly. So if you really believe that eating "just egg whites" isn't fattening, we've got a bridge we can sell ya. Eggs are high in saturated fat and are completely disgusting when you think about what you are eating. Try that for once. Actually think about what you are eating! You will pee in your pants when you see how much weight you lose from giving up dairy. The fat in cheese is what gives it the taste and texture we love. Of the calories found in cheese, 70 to 80 percent come from fat. Even if you're buying the low-fat, part-skim nonsense, more than half the calories come from fat. Fat free? Give us a freaking break! Remember what milk is for. It is designed to fatten up baby cows. Do you really believe it can be made fat free? Get your head out of your ass. Milk = fat. Butter = fat. Cheese = fat. People who think these products can be low fat or fat free = fucking morons. Luckily, there are many alternatives to dairy products. Not only do grocery stores carry these items, but many coffee shops now offer soymilk and some bakeries are selling dairy-free desserts. A personal favorite-tasting milk substitute is Rice Dream (Original Enriched), which is fortified with vitamins and calcium. But feel free to experiment until you find your own favorite brand. Remember to read the ingredients. Avoid the milk substitutes that contain sugar. Instead of butter, try Earth Balance Natural Buttery Spread or Soy Garden Natural Buttery Spread, both made from nonhydrogenated oils. Can't live without ice cream? You don't have to. Soy Delicious has incredible knock-offs, which are completely dairy free. They even make must-have flavors, such as Chunky Mint Madness, Cookie Avalanche, Rocky Road, and Peanut Butter Zigzag. They also have a line of "ice creams" and sorbets that are fruit-sweetened! Dairy and sugar free! Too exciting for words! We're also huge fans of Double Rainbow Soy Cream, another amazing ice cream alternative. Are you a cheese addict? No problem. Follow Your Heart's Vegan Gourmet makes a kick-ass substitute in mozzarella, Monterey jack, and nacho. It even melts! It rules. Beware of the many brands that tout themselves as "soy cheese," leading consumers to believe they're dairy free. When you get past the misleading packaging and actually read the ingredients, you'll discover sneaky dairy ingredients like whey or casein. Steer clear. Other brands are completely dairy-free, but they taste like shit. Need eggs in your life? Easy peasy. Egg Beaters are made of real eggs, so they're a gross no-no. But if you pan-fry House Tofu Steak (slice it in half first) and add a little soy butter, salt, pepper, and ketchup, you've got yourself a fried "egg." There's also an egg substitute in powder form for cooking and baking called Ener-G egg replacer. And many markets sell a pretty good tofu "egg" salad. As the demand grows for healthy, yummy, animal-free, dairy-free products, more companies will supply us with these foods. So let your consumer dollars voice your desire, and your body will be rewarded. And don't be shy. If your grocery store doesn't carry something you want, open your fat mouth and ask for it. Chapter 6 You Are What You Eat N ow would be a good time to reflect on the old adage, "You are what you eat." This statement, in all its simplicity, is brilliant. You are what you eat. You are a human body comprised of organs, blood and guts, and other shit. The food you put into your body works its way through your organs and bloodstream and is actually part of who you are. So every time you put crap in your body, you are crap. If Chapters 4 and 5 didn't convince you to avoid eating animal products (crap), maybe this will. Even knowing how abysmal the living conditions are for animals on factory farms, you cannot begin to imagine what the slaughter practices are like. "Humane" protocol calls for animals to be "stunned" before they are slaughtered. For cows, this means getting a metal bolt shot into the skull and then retracted. When done properly, using working equipment, this renders the cow unconscious. But time is money, and slaughterhouses operate at lightning speeds, some killing one animal every three seconds. Because thousands of frightened, struggling cows are not easy to stun, it is extremely common for a "stunner" to miss his mark. Panicked hogs, also difficult to "hit," are stunned with an electric device. And if the jolt is too high, it bruises and bloodies the hogs' flesh (bad for business). Because business comes first on factory farms, the jolt is lowered, despite the fact that it doesn't properly stun the hogs. Stunned or not, cows and hogs are then "strung up" from the ceiling by a chain attached to their leg(s). In theory, while they dangle there, they are supposed to be unconscious. But often they are fully conscious, struggling, screaming, and fearfully staring at the workers while they have their throats stabbed open. Next, they travel along a "bleed rail," where they should bleed to death. But again, these large, frightened, struggling, conscious animals are difficult targets and the "stickers" (workers who cut their throats) don't always get a "good cut." Before cows can bleed to death, they are sent on their way to the "head-skinners," where the skin is sliced from their heads while they are still conscious. Of course, this is excruciatingly painful, and the cows kick and struggle frantically. To avoid getting injured by the struggling animal, workers will sometimes sever the spinal cord with a knife blow to the back of the head. This paralyzes the animal below the neck so that the worker is safe. But these cows can still feel their skin being sliced away from their faces. Next, their legs and head are chopped off, their entrails removed from their bodies, and then, finally, they are split in half. Often before hogs can bleed to death, they are dunked fully conscious into 140-degree scalding water to remove the hair from their bodies. Chickens, because they are so overcrowded and stressed, frequently peck each other and factory farm workers, so the ends of their beaks are literally chopped off their faces. Even though they currently comprise more than 95 percent of all animals slaughtered for food, Congress exempted chickens (and turkeys) from the Humane Slaughter Act, so there is no requirement to stun them (not that it would matter, anyway). But because it is easier to handle chickens that aren't fighting for their lives, their heads are sometimes dragged through a water bath that has been electrically charged. This paralyzes the birds, but does not render them unconscious. They are snatched up, shackled upside down, and their throats are slashed by machine at the rate of thousands per hour. Next, they are dunked in scalding water to loosen their feathers. Again, they are supposed to be dead at this point, but if the machine misses its mark, or the chickens haven't bled to death, they are "boiled" alive. Then they are placed into a series of machines that literally beat their feathers off of them, still alive and having just been scalded. All the while, they are being handled like rubber toys: grabbed by their necks, feet, or wings and thrown around. You get the idea. In egg-laying factories, male baby chicks are completely useless to farmers because they don't produce eggs. So workers snatch up chicks speeding by on a conveyer belt, quickly glance at their undersides, and then toss the "useless" males into the garbage. Yes. Literally. Millions of male baby chicks are piled on top of each other in garbage dumpsters—left to die. In her book, _Slaughterhouse,_ Gail Eisnitz, chief investigator for the Humane Farming Association, interviewed dozens of slaughterhouse workers throughout the country. _Every single one_ admitted to abusing animals or neglecting to report those who did. The following are quotes from slaughterhouse workers taken from her book. (They are quite graphic and difficult to read, but we implore you to read each one. It is important to know what our dietary desires are contributing to. Surely you can endure reading it if animals have to endure suffering it): "I seen them take those stunners—they're about as long as a yard stick—and shove it up the hog's ass. . . They do it with cows, too. . . And in their ears, their eyes, down their throat. . . They'll be squealing and they'll just shove it right down there." "Hogs get stressed out pretty easy. If you prod them too much they have heart attacks. If you get a hog in a chute that's had the shit prodded out of him and has a heart attack or refuses to move, you take a meat hook and hook it into his bunghole [anus]. You're dragging these hogs alive, and a lot of times the meat hook rips out of the bunghole. I've seen hams—thighs—completely ripped open. I've also seen intestines come out. If the hog collapses near the front of the chute, you shove the meat hook into his cheek and drag him forward." "Or in their mouth. The roof of their mouth. And they're still alive." "Pigs on the kill floor have come up and nuzzled me like a puppy. Two minutes later I had to kill them—beat them to death with a pipe." "These hogs get up to the scalding tank, hit the water and start screaming and kicking. Sometimes they thrash so much they kick water out of the tank. . . . Sooner or later they drown. There's a rotating arm that pushes them under, no chance for them to get out. I'm not sure if they burn to death before they drown, but it takes them a couple of minutes to stop thrashing." "Sometimes I grab it [a hog] by the ear and stick it right through the eye. I'm not just taking its eye out, I'll go all the way to the hilt, right up through the brain, and wiggle the knife." "Only you don't just kill it, you go in hard, push hard, blow the windpipe, make it drown in its own blood. Split its nose. A live hog would be running around the pit. It would just be looking up at me and I'd be sticking, and I would just take my knife and—cut its eye out while it was just sitting there. And this hog would just scream." "I could tell you horror stories . . . about cattle getting their heads stuck under the gate guards, and the only way you can get it out is to cut their heads off while they're still alive." "He'll kick them [hogs], fork them, use anything he can get his hands on. He's already broken three pitchforks so far this year, just jabbing them. He doesn't care if he hits its eyes, head, butt. He jabs them so hard he busts the wooden handles. And he clubs them over the back." "I've seen live animals shackled, hoisted, stuck, and skinned. Too many to count, too many to remember. It's just a process that's continually there. I've seen shackled beef looking around before they've been stuck. I've seen hogs [that are supposed to be lying down] on the bleeding conveyor get up after they've been stuck. I've seen hogs in the scalding tub trying to swim." "I seen guys take broomsticks and stick it up the cow's behind, screwing them with a broom." "I've drug cows till their bones start breaking, while they were still alive. Bringing them around the corner and they get stuck up in the doorway, just pull them till their hide be ripped, till the blood just drip on the steel and concrete. Breaking their legs. . . . And the cow be crying with its tongue stuck out. They pull him till his neck just pop." "One time I took my knife—it's sharp enough—and I sliced off the end of a hog's nose, just like a piece of bologna. The hog went crazy for a few seconds. Then it just sat there looking kind of stupid. So I took a handful of salt brine and ground it into his nose. Now that hog really went nuts, pushing its nose all over the place. I still had a bunch of salt left in my hand—I was wearing a rubber glove—and I stuck the salt right up the hog's ass. The poor hog did-n't know whether to shit or go blind." "Nobody knows who's responsible for correcting animal abuse at the plant. The USDA does zilch." Eisnitz chronicled the constant failure of U.S. Department of Agriculture inspectors to stop this abuse and their willingness to look the other way. In addition, she exposed the USDA's blatant tolerance for allowing contaminated meat into the human food supply. Think about it. _Ten billion_ animals a year! Do you think the USDA has enough inspectors to supervise the humane and safe slaughter of _10 billion_ animals a year? Of course the inspectors tolerate abuse and contaminated meat. Imagine the kind of person who would have a job that entailed witnessing the slaughter of thousands of innocent animals every day. Even if every single inspector did a good job (they don't), the factory workers can easily bypass the system. Eisnitz interviewed one worker from a horse slaughterhouse, who said, "Might be part of him's [a contaminated horse] bad, might be the pneumonia's traveled everywhere. I'd drag him back, and my boss would tell me to cut the hindquarters off and bring him into the cooler. The meat's supposed to be condemned, but still you'd cut it up and bag it." When Eisnitz asked, "But don't they have to be stamped 'USDA inspected?' " he responded, "He [his boss] got the stamper. He can stamp it himself when the doc leaves. . . . You take a condemned horse, skin him, cut him up, sell the meat. . . . We've sold it as beef." According to the Congressional testimony of one former Perdue worker, the poultry plants are filthy. She said there were flies, rats, and 5-inch long flying cockroaches covering the walls and floors. Believe it or not, it gets worse: "After they are hung, sometimes the chickens fall off into the drain that runs down the middle of the line. This is where roaches, intestines, diseased parts, fecal contamination, and blood are washed down. Workers [vomit] into the drain. . . . Employees are constantly chewing and spitting out snuff and tobacco on the floor . . . sometimes they have to relieve themselves on the floor. . . . The Perdue supervisors told us to take the fallen chickens out of the drain and send them down the line." A USDA inspector said of the cockroaches, "One time we shined a flashlight into a hole they were crawling in and out, and they were so thick it was like maggots, you couldn't even see the surface." A worker at another poultry plant said, "Every day, I saw black chicken, green chicken, chicken that stank, and chicken with feces on it. Chicken like this is supposed to be thrown away, but instead it would be sent down the line to be processed." Another worker at another plant said, "I personally have seen rotten meat—you can tell by the odor. This rotten meat is mixed with the fresh meat and sold for baby food. We are asked to mix it with the fresh food, and this is the way it is sold. You can see the worms inside the meat." No comment. We are simply speechless. Animals are intelligent, emotional, social creatures. Researchers at Bristol University in Britain discovered that cows actually nurture friendships and bear grudges. One study showed cows displaying excitement while solving intellectual challenges. Chickens are as smart as mammals, including some primates, claims animal behaviorist Dr. Chris Evans of Macquarie University in Australia. They are apt pupils and can learn by watching the mistakes of others. One researcher conducted a study that demonstrated chickens' ability to use switches and levers to change the temperature of their surroundings. A PBS documentary revealed chickens' love for television and music. Pigs can play video games! They've been labeled as more intelligent than dogs and three-year-old humans. They too can indicate their temperature preferences. Even fish have feelings. Dr. Donald Broom, scientific adviser to the British government, explains, "The scientific literature is quite clear. Anatomically, physiologically and biologically, the pain system in fish is virtually the same as in birds and animals." Fish, like "higher vertebrates," have neurotransmitters similar to endorphins that relieve suffering. Of course, the only reason for their nervous systems to produce painkillers is to relieve pain. Animals hear the screaming and crying of other animals being slaughtered and are terrified. They know they are about to be killed and they are panic-stricken. When their young are taken from them, cows kick stall walls in rage and frustration and literally cry with grief. Think of how you feel when you are angry, afraid, and grief-stricken. Bear in mind the physical feelings that accompany these emotions. These emotions—fear, grief, and rage—produce chemical changes in our bodies. They do the same to animals. Their blood pressures rise. Adrenaline courses through their bodies. You are eating high blood pressure, stress, and adrenaline. You are eating fear, grief, and rage. You are eating suffering, horror, and murder. You are eating cruelty. You are what you eat. You cannot be thin and beautiful with a glowing complexion when you eat fear, grief, and rage. Although a minuscule percentage of "meat" in the United States comes from free-range farms, how do you even know it is really free-range? Companies want us to believe that products labeled "free-range" or "free-roaming" are derived from animals that spent their short lives outdoors, enjoying sunshine, fresh air, and the company of other animals. But labels—other than "organic" on egg cartons—are not subject to any government regulations. In addition, the USDA doesn't regulate "free-range" or "free-roaming" claims for beef products. Because there are no agencies governing these claims, do you take the word of someone who makes a living on blood money? And even if the farm was free-range and humane, the animals are still being sent to horrific slaughterhouses. (An undercover video of a kosher slaughterhouse revealed animals suffering the same abuse and torture. Check it out at www.humanekosher.com.) Many animals don't even survive the transport from their factory or free-range farm to slaughter. The only law in existence dictating care for transported animals is related to _train_ transport. But it just so happens that 95 percent of animals are transported by _truck_. It's difficult to believe the new guidelines are being complied with or enforced. Animals receive little to no food or water and no protection from the elements. Millions of animals are dead on arrival or too injured or sick to move. They don't get to stop for bathroom breaks, so the animals are forced to stand in their own urine and feces. In the wintertime, the animals' flesh and feet will actually freeze to the bottom and sides of the truck. So upon arrival, they are literally ripped away from the truck. One worker interviewed by Eisnitz said, "They freeze to that steel railing. They're still alive, and they'll hook a cable on it and pull it out, maybe pull a leg off." Assuming you started with a healthy animal (highly unlikely), you've now eaten hormones, pesticides, steroids, antibiotics, fear, grief, and rage. You are what you eat. But what if the animal wasn't healthy? Animals that are too sick or injured to walk are literally dragged to slaughter, one end of a chain attached to the animal, the other to a truck. The USDA still allowed these animals, referred to as "downers," to be slaughtered for human consumption until 2004. Finally, with the outbreak of more mad cow disease cases (a deadly and incurable disease that can be transmitted to humans through the consumption of cow flesh), they came to their senses. But in 2005, USDA Secretary Mike Johanns announced that downed animals may once again be slaughtered for human food. Thankfully, almost immediately into his presidency, Barack Obama announced that downed cows could no longer be part of the food supply. Hopefully, the ban will be complied with and enforced. If it isn't, in addition to all the other filth you're eating, you're also eating whatever illness the animal had. You are what you eat. (Bear in mind, downed pigs, goats, sheep, chickens, and turkeys can still be killed for human consumption. Cruel and gross.) Let's make believe that all the animals killed for human consumption are healthy, happy, free of antibiotics, steroids, and pesticides and are humanely raised and slaughtered. Pretend you are eating "perfect meat." Great. But what exactly are you eating? "Meat" is the decomposing, decaying, rotting flesh of a dead animal. As soon as an animal dies, it starts "breaking down." How long has passed between when the animal was slaughtered and the time you are eating it? It could be weeks, even months. You want to put a dead animal corpse—that has been rotting away for months—in your mouth? In your body? Because meat is muscle tissue, it oxidizes in an open environment and turns brown. So most meat markets will scrape off the brown parts to make it look more appealing. Another trick of the trade is using tinted lighting in open meat cases to enhance the meat's color. Restaurants and ranchers might call their meat "aged to perfection," but no matter how you slice it, it's still a putrefying corpse. You are what you eat. Just because you can't see what's happening doesn't mean it doesn't exist. Every time you have a craving for meat or dairy, remember what goes on inside every slaughterhouse, processing plant, and grocery store. Linda McCartney said it best: "If slaughterhouses had glass walls, we'd all be vegetarians." For added motivation with your new lifestyle, visit GoVeg.com and order a free vegetarian starter kit. So now you are officially vegan, a person who doesn't eat _any_ animal products. No meat, chicken, pork, fish, eggs, milk, cheese, or butter. Feel great about it. Yes, it is challenging to avoid these foods, but you will reap the karmic rewards of being vegan (like being skinny). For starters, you're sparing the lives of at least ninety animals a year. And every environmentalist knows that factory farming is completely destroying the environment. As ridiculous as it sounds, the methane resulting from the burps and farts of 10 billion animals a year is directly responsible for global warming. The urine and feces are polluting and contaminating soil and water all over the country. According to the Environmental Protection Agency, they are the largest polluters of U.S. waterways. Moreover, the amount of land, food, water, and energy used to raise 10 billion animals a year for slaughter could be used to grow food for _all of the starving people in the world._ That's right—you being vegan is actually a step toward ending world hunger. Now that's some serious skinny karma. So you shouldn't eat cows, chickens, pigs, fish, milk, cheese, or eggs. So what the hell should you eat? Pretty much everything else: fruits, vegetables, legumes, nuts, seeds, and whole grains. Deep down, you've known all along that these foods are best for you; now it's time to get back on track. Our diets have strayed so far off course from where they belong; we've allowed meat to take center stage, with grains and vegetables playing supporting roles. Wrong, wrong, wrong. There is a plethora of great-tasting, healthy, wholesome foods that you've likely been neglecting for years. Well, those days are over. Can you remember back to your grade-school days when you learned about photosynthesis? Plants store the sun's energy, which we receive by eating them. If you can, just picture the light energy from the sun beaming down to the vegetables and fruits, and as we eat those foods, imagine that energy being transmitted into our bodies. Our nervous systems are maintained and stimulated by this light. What an amazing gift from nature—to be able to eat such pure foods that give our bodies so much! However, be advised, all fruits and vegetables are not created equal. Plants need vitamins and minerals to function and grow properly. When they are sprayed with pesticides and grown in chemically treated soil, they won't absorb all the proper nutrients. This results in a loss of enzymes. So, organic fruits and vegetables—ones that have been grown in pure, untreated soil and without pesticides—have far more enzymes than their conventionally grown counterparts. Any scientist can tell you that food has an "energy" or "life" to it. Anyone with common sense can tell you that eating a live, fresh fruit is healthier than eating a cooked, canned, preserved one. Why? Because this "life" comes from the plant's energy, nutrients, phytochemicals, and enzymes. Enzymes are living biochemical factors that we need to survive. They are critical for digestion, breathing, reproduction, and the functioning of DNA and RNA. They also help repair and heal our organs, detoxify our bodies, carry out our nerve impulses, and help us think. There are three types of enzymes: metabolic, digestive, and food enzymes. Fortunately, we produce our own metabolic enzymes, which run the whole body, maintain our health, and defend us from illness and infection. But our own enzyme supplies are limited. So to continue healthy bodily functions, we need to supplement with food. When we eat, our bodies release digestive enzymes to break down the food. If we eat foods devoid of enzymes, such as meat, processed food, and even just overcooked food (high temperatures destroy enzymes), our bodies have to work much harder. Harder work means using more of our precious enzymes. Over time, this can result in an enlargement of the digestive organs and the endocrine glands. (Studies have shown that the increased weight of these organs accompanies obesity.) This lack of enzymes can also cause a disruption in the body's ability to make enough metabolic enzymes. But when we eat foods high in enzymes, such as fruits, salad, or lightly steamed veggies, we get an enzyme boost along with the meal, so our bodies don't have to work so hard. There is no greater defender of our bodies than enzymes. When not in use for digestion, enzymes are busy repairing and cleaning our bodies. So don't go throwing your enzymes away on shit! So how do we get these enzymes into our bodies? We just need to make the following foods part of our daily diets: fruits (especially pineapples, papayas, bananas, and mangos), raw or lightly steamed vegetables, raw nuts and seeds, wheat grass, sea vegetables, garlic, and legumes. Juicing is a great way to detoxify your body and get a lot of enzymes, but you must drink it right away. As soon as a fruit is peeled, or cut, or juiced, it begins to lose its enzymes. So, buying a gallon of fresh-squeezed juice isn't as beneficial as making your own daily. Packaged juice has been pasteurized, and the heat destroys the enzymes. Granted, it's still better to drink pasteurized juice than soda. So if you can't juice for yourself, do the best you can. Well, there you have it. Fruits and vegetables are the answer. And unless you are an idiot who wants cancer, obesity, and enlarged organs, organic is the way to go. You are what you eat. Chapter 7 The Myths and Lies About Protein I f we had a penny for every time some meathead asked us, "So where do you get your protein?" we'd be richer than Oprah. Have you ever, ever, ever, in your entire life, heard of anyone suffering from a protein deficiency? Did you ever see an elephant, moose, or giraffe jonesing for a protein fix? If you weren't blacked out on bourbon for the past three chapters, you should know by now: It is a complete myth that we need a massive amount of protein. Too much protein—especially animal protein—can impair our kidneys; leach calcium, zinc, vitamin B, iron, and magnesium from our bodies; and cause osteoporosis, heart disease, cancer, and obesity. In addition, high amounts of protein can damage our tissues, organs, and cells, contributing to faster aging. Yikes! Know this: People in other cultures consume half the amount of protein that we do, yet they live longer, healthier lives. Although too much is harmful, protein is still vital to our health. Protein produces enzymes, hormones, neurotransmitters, and antibodies; replaces worn out cells; transports various substances throughout the body; and aids in growth and repair. So how much protein do we really need? Well, depending who you ask, that number varies anywhere from 18 to 60 grams a day. But one thing is certain: Vegetarians need not worry. Researchers at Harvard found that vegetarians (who don't live on junk food) get adequate amounts of protein in their diets. The American Dietetic Association reports that eating a vegetarian diet provides twice the amount of protein needed daily. In his book, _Optimal Health,_ Dr. Patrick Holford explains that "most people are in more danger of eating too much protein than too little." So pick something else to be neurotic about. How do vegans get protein? Simply. We eat lentils, beans, nuts, seeds, fruits, vegetables, whole grains, and soy products (edamame, tofu, imitation cheeses and meats). When you eat well-balanced meals consisting of these foods, you are guaranteed to get sufficient protein. For example, for lunch, if you had a soy burger on a whole grain bun with avocado and tomato and a small side salad, you'd get 22 grams of protein. See how easy? If you want an extra boost, treat yourself to spirulina, a high-protein algae that contains omega-3 and omega-6 fatty acids, B-12 (important for vegetarians), enzymes, and minerals. It also supports the immune system, fights cancer, and helps with hypoglycemia, anemia, ulcers, diabetes, and chronic fatigue syndrome. Spirulina also contains all nine essential amino acids. Amino acids, huh? Yep. There are twenty amino acids. Our bodies produce eleven, and the other nine essential amino acids can be obtained through food. Amino acids are the building blocks of protein. And yes, protein does build muscle. But even if you work out and want to build muscle, you don't need to overdose on animal protein (a ridiculous myth perpetuated by the health club industry). Bear in mind, some top athletes are vegetarians: Chris Campbell is an Olympic wrestling champion; Keith Holmes, a world-champion middleweight boxer; Bill Mannetti, a power-lifting champion; Bill Pearl, a four-time Mr. Universe; Andres Cahling, a champion body-builder and Olympic gold medalist in the ski jump; Art Still, a Hall of Famer and MVP defensive end for the NFL; Martina Navratilova, a tennis champion; and Dr. Ruth Heidrich, a six-time Ironwoman, age-group record holder, USA track and field Master's Champion, and vegan. Another common myth that has since been debunked is the "food combining" theory. Animal flesh proteins are "complete," meaning they contain all nine essential amino acids in amounts similar to those found in human flesh. Plants have all these amino acids, too, just in slightly different amounts. It was previously believed that in order to create complete proteins from vegetarian foods, you needed to combine them in specific ways. For example, it was said rice and beans had to be eaten together to maximize their protein potential. However, it is now known that eating a variety of foods from plant sources provides all the building blocks we need. Further, the microorganisms and recycled cells in our intestinal tracts make complete proteins for us. All we have to do is eat healthy, balanced diets. An integral part of any healthy, balanced diet is fat. Don't cringe. Fat doesn't always mean fattening. Essential fatty acids provide us with energy and offer protection from heart disease, stroke, and high blood pressure. They also combat allergies, premenstrual syndrome, arthritis, and skin problems. Our brilliant bodies make all the essential fatty acids we need, except for two: linoleic and linolenic acids, also known as omega-3 and omega-6. These _good fats_ are found in olive oil, sesame oil, canola oil, flaxseed oil, hempseed oil, evening primrose oil, raw nuts and seeds, and avocados. So quit listening to all the stupid bitches who boycott nuts, oils, and avocados because they think they're fattening. Even though they're high in fat, they will not make you fat (unless you totally overdose on them). Unsaturated fats such as these are good for your body, and when eaten as part of a well-balanced vegan diet, they don't make you fat! It's the saturated fats, found in meat, dairy, and hydrogenated oils that make you fat. Think about the source of the oils or fats and use your head. Do you think an avocado, which is a fruit, is going to turn you into a hippo? Common sense, bitches. Chapter 8 Pooping P inch a loaf. Lay cable. Drop the kids off at the pool. Let's face it; there is no greater pleasure than taking a big, steamy dump. But shitting isn't just for kicks. It is a vital tool for weight loss and optimal health. Basic math, girls. How much are you putting in your mouth, and how much is coming out your ass? Now that you've learned the right foods to eat and which ones to avoid, you should be a dynamo in the bathroom. But if your hiney is only expelling little rabbit turds, something's gotta give. Earlier, we mentioned that drinking lots of water helps rid your body of waste. We can't emphasize the importance of this enough. Drink, drink, drink. But if you want to take tyrannosaurus-sized dumps, it's also imperative to eat foods rich in fiber, like whole grain cereals and breads, brown rice, corn, barley, rye, buckwheat, millet, oats, fruits, vegetables (especially root vegetables, like carrots), beans, and seeds. Avoid foods that have little or no fiber, like meat, eggs, cheese, milk, and processed, refined foods. These can clog up your ass. (It is a myth that bananas are binding. Eat 'em.) Fiber isn't just for shits and giggles, either. It offers protection from appendicitis, Candida, heart disease, high blood pressure, high cholesterol, diabetes, gallstones, irritable bowel syndrome (IBS), and colitis. Fibrous foods also help normalize our blood-sugar levels, satiate food cravings, and make us feel fuller so that we don't overeat. Fiber even fights colon and colorectal cancer, prostate cancer, and breast cancer: If we don't make ca-ca quickly enough, our putrefying food stays in our bodies, increasing the likelihood of the production of carcinogenic substances. So eat your fiber, and crap like a champ. Another way to get your bowels brewing is to pay special attention to the order in which you are eating foods. For example, foods that digest quickly and easily should be eaten by themselves and early in the day. Fruit for breakfast. Salad and/or vegetables for lunch. These foods will pass through your body at lightning speeds. Dinner should be your "heaviest" meal. Follow these simple rules and you'll be depositing six-inchers in no time. If you're already a quality dumper, feel free to disregard this paragraph. But, if you still need an extra kick in the ass, up your bean intake. Beware: you might have a mudslide in your pants if you're not careful. If you're not accustomed to beans, ease in slowly and be sure you are near a toilet. If your deuce-dropping still needs work, do not take laxatives. Yes, they make you poop, but they don't solve the underlying problem of why you're not pooping in the first place. Most laxatives are gastro-intestinal irritants—even the natural ones. Stop looking for a quick fix. Just continue to drink a lot of water, exercise, and eat right, shitheads. Chapter 9 Have No Faith: Governmental Agencies Don't Give a Shit About Your Health # The USDA: It's Not What You Think P resident Abraham Lincoln founded the U.S. Department of Agriculture in 1862—when the majority of people were farmers and needed to exchange information about seeds and crops. In other words, the USDA was created to help farmers. According to its web site, now, among other things, the USDA is responsible for "the safety of meat, poultry, and egg products." Hmm. That's weird. 'Cause many high-ranking staff members at the USDA were employed by, or are otherwise affiliated with, the meat and dairy industries. And if the group responsible for "the safety of meat, poultry, and egg products" is run by people from the same industries they're supposed to be protecting us from . . . well, that would be a conflict of interest. _And it is._ An enormous, ridiculous, outrageous, catastrophic conflict of interest. One former USDA Secretary was forced to resign amid charges of accepting illegal corporate gifts from seven different companies. He was indicted on thirty-nine felony counts, including tampering with a witness; accepting illegal gratuities; making false statements; and violating the Meat Inspection Act of 1907. (Tyson Foods, one of the companies that admitted to giving the Secretary corporate favors, was required to pay $4 million in fines and endure four years' probation. A mere slap on the wrist, when the USDA could've barred Tyson from selling food to military bases and schools. That would've really stung, considering Tyson sold more than $10 million worth of food to the Defense Department alone in 1996. But friends don't treat each other that way.) President George W. Bush's Agriculture Secretary from January 2001 until January 2005, Ann Veneman, not only had ties with the company responsible for producing the controversial bovine growth hormone, (BGH), but she was also linked to a major meatpacking corporation. The buck doesn't stop there. She employed a spokeswoman who was the former public relations director for the Cattlemen's Beef Association, a chief of staff who used to be its head lobbyist, a former president of the National Pork Producers Council, and former executives from the meatpacking industry, just to name a few. # Safety Last W ith that in mind, it's no wonder Veneman vetoed a program that would test all U.S. cattle for mad cow disease. In fact, out of the 35 million cattle slaughtered in 2003, the USDA only tested 20,000 for mad cow disease. (Japan tests _all_ of their cattle killed for human consumption.) Of course it wouldn't be in a rancher's best interest to test all of his cattle. If they were inflicted with mad cow disease, he couldn't sell their meat, and he'd lose money. Heaven forbid the USDA risk a rancher's profits. So, in order to appear somewhat concerned about the prevention of mad cow disease, the USDA often refers to an FDA ban, which prohibits the feeding of ground-up cattle meat to live cattle. Big whoop. Banning cannibalism is a no-brainer. But why even bother banning cannibalism when they still allow the feeding of _cattle blood_ to young calves? Stanley Prusiner, a Nobel Prize Winner for his work on mad cow disease, refers to this practice as "a really stupid idea." Think about it: A cow dies from mad cow disease, but no one knows, because it wasn't one of the .0005714% percent tested. Cattle ranchers are now forbidden to grind up this dead cow and feed it to other cows. But, they can give its blood to calves as part of their feed. How fucking stupid, disgusting, and dangerous is that? The USDA also likes referring to another "safety" program in place, called The National Animal Identification System (NAIS). The NAIS is a system for identifying an animal's origin so that if its meat is found to be contaminated, it can be traced back to a specific farm. (Forget testing as a preventative measure. Implement a system for after someone eats contaminated meat and we need a recall.) Participation in this program is voluntary. Wow, the USDA sure has tough rules governing the safety of our country's meat. The USDA's web site describing the NAIS actually has a section on "confidentiality." It reads, "The NAIS will contain only information necessary for animal health officials to be able to track suspect animals and identify any other animals that may have been exposed to a disease. . . . To help assure participants that the information will be used only for animal health purposes, the information must be confidential. USDA and its State partners will work to protect data confidentiality." What the fuck? The USDA will protect the data confidentiality of farms that are supplying the public with contaminated meat? Why don't they just give all the ranchers blowjobs, too? Many savvy consumers are catching on, and they know they cannot trust the USDA. According to the Organic Consumers Association, "Lester Friedlander, a former USDA veterinarian, says he was told by USDA officials as far back as 1991 that if his testing ever found evidence of Mad Cow disease, he was to tell no one. He and other scientists say they know of cases where cows tested positive for the disease in laboratories but were ruled negative by the USDA." Trust no one! Illegal hormones are regularly pumped into veal calves, which are suspected of increasing the growth of cancer cells in the humans who eat them. The USDA has not only been accused of overlooking these practices, but also of falsifying lab results, altering records, and pressuring staff to lie about events. Even the selfish whores who eat veal don't deserve that. # Business First N one of us deserved to be deceived all these years by the preposterous USDA Dietary Guidelines and Food Pyramid, either. In 1998, the Physicians Committee for Responsible Medicine (PCRM) filed a federal lawsuit against the USDA and the Department of Health and Human Services. PCRM claimed that federal laws were violated when the USDA selected six out of eleven people with financial ties to various food industries to serve on the Dietary Guidelines Advisory Committee. The committee members' affiliations included the American Meat Institute, National Livestock and Beef Board, the American Egg Board, the National Dairy Promotion and Research Program, the National Dairy Council, Dannon Company (yogurt), Mead Johnson Nutritionals (milk-based infant formulas), Nestlé (milk-based formulas, ice cream, condensed milk), and Slim-Fast (milk-based diet products). How dare they? (On a sidenote, PCRM also charged that the Dietary Guidelines —which recommended dairy products—were racially biased, because most nonwhites are lactose-intolerant. According to Johnson & Johnson, lactose intolerance affects "over 50 percent of the Hispanic American population, 75 percent of Native Americans, 80 percent of African Americans, and 90 percent of Asian Americans." Why does Johnson & Johnson care about the millions of minorities suffering from lactose intolerance? Because they can target these individuals for buying Lactaid, a product they hawk for aiding in dairy digestion. Even though you are lactose intolerant and your body thoroughly rejects dairy products, eat them anyway. Just buy and take our drug so you don't feel sick afterwards. Ugh, that just makes us sick with rage.) Got $19 billion? The milk industry does, so they've got the USDA in their back pocket. The California Milk Processor Board (CMPB) was established in 1993 to increase milk sales in California. They were responsible for the campaigns that targeted children: "Got milk?" and "Milk. It does a body good." The CMPB is funded by all California milk processors, but administered by the California Department of Food and Agriculture. The National Fluid Milk Processor Promotion Board (Fluid Board) conceived of the "Milk Mustache" campaign, which targets young adults. The USDA's Agriculture Monitoring Service administers the Fluid Board. Meaning, in essence, the California Department of Agriculture and the USDA are managing advertising campaigns for the milk industry. Under the guise of advancing health, they managed to dupe President Bill Clinton, while he was in office, into posing for their ads. They also had the audacity to feature the Secretary of Health and Human Services, Donna Shalala, sporting that stupid "milk mustache." The Secretary of Health and Human Services using her status and title to promote a commercial product! Would she appear in ads for Pepsi or Nike? Say it out loud: conflict of interest. They've even got the U.S. surgeon general in on the act. In the first-ever report on "the state of the nation's bones," the U.S. surgeon general warned of an impending "osteoporosis crisis" expected by the year 2020. In order to ward off this potential disaster, the Surgeon General's report recommended three glasses of milk a day. Guess who issued the report? The Department of Health and Human Services. Trust no one. The horrors committed by the USDA could fill an entire book. But we shouldn't be surprised. Although they don't list it as part of their primary mission statement, the USDA does admit to being "committed to helping America's farmers and ranchers." The same USDA responsible for "the safety" of meat, poultry, dairy, and eggs also promotes the sale of them. In fact, they even go so far as to purchase the products themselves, using _our_ tax dollars. The USDA will spend $30 million a year on beef buyouts alone. Another $30 million of _our_ hard-earned money goes toward pork purchases. Wow. It must be nice for these industries to have the USDA bailing them out whenever they have a surplus of items. What, exactly, do they do with all this food that _we_ pay for? # All in a Day's Work E ver hear of the National School Lunch Program (NSLP)? It's a nation-wide $4 billion scheme that allows the USDA to buy up all this meat, milk, and cheese with our tax dollars, and then dump this crap into the bodies of more than 26 million school children. Ever wonder why school lunches are _required_ to include milk? The NSLP directly benefits the meat, dairy, and poultry industries at the expense of our nation's children. In 1999, a ground beef plant in Texas failed a series of USDA tests for salmonella. The tests showed that as much as 47 percent of the company's ground beef contained salmonella—a proportion 5 times higher than what USDA regulations allow. Despite this, and the fact that high levels of salmonella in ground beef indicate high levels of fecal contamination, the USDA continued to purchase thousands of tons of the meat for distribution in schools. In fact, this company was one of the nation's largest suppliers for the school meals, providing as much as 45 percent of the program's ground meat. Contamination aside, according to Michele Simon of the Center for Informed Food Choices, "One evaluation of the commodity foods program estimates that 70 percent of the items offered exceed the U.S. dietary guidelines for fat." For decades, consumer advocacy groups have been horrified by this unhealthy, profit-driven arrangement. With the backing of countless parents, physicians, and nutritionists, they have battled to get soy milk and other healthier choices approved by the USDA for use in school lunches. But the USDA (a.k.a.: the beef, pork, poultry, and dairy industries) wants no part in this, of course. The USDA has fifteen food-assistance programs, including ones for the elderly, homeless, military, and poor. It is estimated that one in five Americans will take part in this $41.6 billion program., Sounds like the USDA is helping to feed a lot of people, right? Right. They are feeding them fattening, unhealthy, artery-clogging, heart-stopping, acid-producing, contaminated meat, poultry, and dairy—with our money. How generous. # Organic or Not? I t's not enough that they dictate all things meat and dairy, the USDA even sticks its big nose into our organic products, too. In April 2004, the USDA made sweeping changes to their National Organic Program (NOP) standards. The new rules infuriated organic farmers and consumers because: Livestock were allowed to eat non-organic fishmeal, even if it contained toxins or synthetic preservatives; cows and calves given growth hormones, antibiotics, or other drugs could still provide the public with "organic" milk, as long as a year had passed since the drugs were administered; pesticides could be used even if they contained unknown inert ingredients as long as a "reasonable effort" had been made to identify them; and seafood, pet food, clothing, fertilizers, and body care products could be labeled organic without being monitored by the USDA. Not only were people livid with the actual changes, but also with the decision-making process. By law, these types of regulatory changes are required to undergo a period of public comment before being enacted. There was no comment period, just an announcement of changes after the fact. According to Ronnie Cummins, national director of Organic Consumers Association (OCA), "Rather than comply with regulations which uphold the integrity of organic food, corporate-run factory farms, who want a piece of the $11 billion a year organic industry, are manipulating the USDA and Congress to change the rules to suit their toxic-industrial style of farming. Allowing non-organic, and potentially genetically engineered feed to be included under the definition of "organic" is a major setback for the integrity of what is the fastest-growing sector of the food industry in this country." Thanks to the phone calls, letters, e-mails, and faxes of many pissed off consumers, the USDA reversed all these changes in May 2004. Even so, many people are still mistrustful of the USDA. Nonprofit group, The Center for Food Safety (CFS), claims that the USDA may be allowing "sham" certifiers under the umbrella of the National Organic Program (NOP). Their suspicions were aroused by the high volume of certifications issued within a short time. These worries were heightened when the USDA refused to provide CFS with requested documents, even though they were required to do so under the Freedom of Information Act. Other environmental groups along with the OCA have joined a lawsuit against the USDA. Among their complaints was the fact that the USDA's NOP created an additional category of certified products, which directly opposes legislation put in place by Congress. They state, "When Congress has spoken clearly on a subject, USDA has no discretion to rewrite the statute making exceptions that dilute the standards of the Act." Can you believe the nerve of these USDA fuckers? Going against laws created by our elected officials and making up their own rules? It's fucking mutiny, is what it is. Trust no one. When buying organic foods, look for certification from anyone other than the USDA. Oregon Tilth, California Certified Organic Farmers, Marin Organic Certifying Agency, and Demeter Certified Biodynamic are all reputable. Sometimes a product will be certified organic by the USDA and another party. So don't rule it out just because the USDA certifies it. Surely you've seen the "organic" Horizon brand of dairy products in your grocery store? It is the nation's largest supplier of organic dairy products. Well, it just so happens that Horizon has been accused of violating organic standards. The Cornucopia Institute, a watchdog group in support of organic agriculture, filed two complaints with the USDA. They allege that two major farms that supply Horizon with milk are confining cows in an industrial setting and denying them access to pasture, yet are still calling their products organic. Why is all this allowed to happen? Don't our elected officials know what's going on? Why don't they try to stop this? Some do. But many politicians are in bed with the evil industries. McDonald's alone has made close to $2 million in campaign contributions; the National Cattlemen's Beef Association nearly $1.5 million; and the National Restaurant Association more than $3.1 million. Hate to sound like a broken record player, but trust no one. # Is Everyone in the FDA on Drugs? T his greed-induced immorality isn't applicable just to Congress or the USDA. The Food and Drug Administration (FDA) is a pathetic facade, too. In 1990, the Monsanto Company sought FDA approval for Posilac, a commercialized form of bovine growth hormone (BGH, used to increase cows' milk production). Even though the test study linked the hormone to prostate and thyroid cancer, the FDA still approved Posilac. Of course, these damning test results weren't made available to the public until 1998, when a group of scientists conducted an independent analysis of the study. They found that the FDA never even reviewed Monsanto's findings! More recently, BGH has been linked to increased levels of Insulin Growth Factor-1, a cancer promoter. But the FDA has no interest in these findings, either. Or the fact that both the World Trade Organization and The United Nations Food Standards Body refuse to endorse the hormone's safety. And they certainly don't mind that BGH milk is banned in all of the European Union, Canada, Japan, and every other industrialized country in the world. Fucking Dumb Asses. Why would the FDA knowingly allow a cancer-causing hormone into our milk supply? One theory highlights the fact that the FDA Deputy Commissioner at the time of the Posilac approval was a former Monsanto lawyer. And, during his tenure at the FDA, this same deputy commissioner wrote the policy exempting BGH from special labeling. Yet, fingers also point to a former top scientist with Monsanto, who was hired by the FDA to review her _own_ research, conducted while she was working for Monsanto. This little beauty also allowed a hundred-fold increase of antibiotic residues in milk. Fear not. The FDA's bad behavior isn't singular to the dairy industry. It also has a sketchy history with monosodium glutamate (MSG). One former FDA Commissioner testified before the Senate Select Committee on Nutrition that MSG was safe, citing four sources. It was later discovered that two of the studies were nonexistent, and the other two were incomplete Secrets and lies. It's just too much to bear. So let's also play the "I'm not telling" game. Ever see the words "natural flavors" on food packaging ingredient lists? Yeah, that's because the FDA allows companies to be vague and doesn't require them to tell us exactly what we're eating. The FDA has a list of approximately 300 foods that meet a "standard of identity," meaning, companies aren't required to spell out their ingredients. For example, ice cream manufacturers can use any of twenty-five specified additives without listing them in their ingredients. Who wants to put something into his or her body without even knowing what it is? By now, Chapter 9, _you_ better fucking not! # You Are Your Only Chance I f you want to get skinny, you can only rely on yourself. If you adapt only one practice from this book, let it be this: _Read the ingredients._ Forget counting carbs, adding calories, and multiplying fat grams. Just read the ingredients. It doesn't matter how many calories or carbs or fat grams something has. _It just doesn't matter._ You don't need the government's asinine recommended daily allowances (RDA) to tell you how to eat. Just read the ingredients. If they are healthy, wholesome, and pure—dive in. If there is refined sugar, white or bleached flour, hydrogenated oils, any animal products, artificial anything, or some scary-looking word that you don't know—don't eat it. We can't make it any simpler. Just read the ingredients and completely ignore all the other gibber jabber bullshit the government calls for on the packaging. Fuck them. Trust no one. Get skinny. And no matter what, do not fall prey to clever advertising used on the packaging. The companies that call their products "wholesome" or "nutritious" can be the same ones that add hydrogenated oils, artificial flavors, or synthetic preservatives. Just read the ingredients of everything you buy. It's not a big deal, assuming you are literate. There is so much bureaucracy and red tape surrounding health-related government agencies that you are much better off fending for yourself. After all, why would anyone take nutritional advice from organizations that let color dyes, hydrogenated oils, chemical preservatives, and artificial flavors into the food we eat? # The EPA Makes Us Sick S tarLink corn, a genetically modified organism, contains an insecticidal protein, deemed unsafe for human consumption. But the Environmental Protection Agency allows the use of StarLink for livestock feed. Let humans eat the animals who ate the corn? That's safe? Duh. Clearly, nothing is sacred to the group that allows _rocket fuel_ in our milk supply. Yeah, you heard right. Rocket fuel. In milk. Thanks to the Pentagon, ammonium perchlorate, the main explosive component in rocket fuel, has been lurking around our environment for decades. It finds its way into water used for growing feed crops for cattle. Cows eat these contaminated crops, with the result being contaminated milk. Whether you are drinking milk or eating dairy products made with this milk, you are ingesting perchlorate. And the EPA actually makes allowances for a "provisional daily safe dose." We're sorry, but where we're from—Earth—there is no acceptable amount to ingest where explosive components are concerned. Even if you believe any amount to be safe, tests revealed milk perchlorate levels well above the EPA's index. Studies conducted by the Environmental Working Group (EWG), a nonprofit, non-partisan organization, found _every single_ milk sample tested in Texas to be contaminated. California's own Food and Agriculture Department found that milk off the grocers' shelves had _five times_ the EPA's "safe dose" of perchlorate. But, of course, the California Food and Agriculture Department did not release these results. Instead, they were brought to light by the EWG. Although both the dairy industry and government agencies acknowledge that there could be some health risks associated with perchlorate, they maintain that we should keep drinking milk for its "calcium, protein and minerals." We'll let you use your own heads on this one. Regardless of your political affiliation, please know this: The Bush Administration continuously asks for exemptions on behalf of the military and chemical companies, allowing them to continue this contamination and to shirk responsibility for cleanup. In fact, the Bush administration's EPA has been widely criticized on many counts of environmental pollution that affect our food and water supply. Like the USDA's pathetic voluntary program, the EPA has its own version of letting agribusiness trample all over public health and safety. Collaborating closely with the U.S. Poultry and Egg Association and The National Pork Producers Council (NPPC), the EPA developed a _voluntary_ air-monitoring program. Disregard the notion that the EPA blames factory farming for 73 percent of all ammonia (fumes from all the shit and piss of farm animals) released into the air nationwide. Never mind the fact that the EPA names factory farming to be the single largest contributor of polluted American waterways. Factory farmers do not have to submit to EPA monitoring programs. If it pleases them, they can volunteer. How civilized. Outraged by the EPA's lack of enforcement, opponents point out that the factory farming industry made $3.46 million in campaign contributions, benefiting mostly Republican federal candidates. The NPPC even went so far as to present President Bush with its "Friend of the Pork Producer" award in 2004, thanking him for his help in "shaping environmental policies impacting agriculture." Yeah, um, thanks for that. # Trust No One W hether you love him or hate him, President Clinton's administration tried to "implement a tough, science-based food inspection system," according to Eric Schlosser, bestselling author of _Fast Food Nation_. Sad to say, however, these attempts were squashed when the Republican party gained control of Congress in 1994. Schlosser revealed, "The meatpacking industry's allies in Congress worked hard to thwart modernization of the nation's meat inspection system. A great deal of effort was spent denying the federal government any authority to recall contaminated meat or impose civil fines on firms that knowingly ship contaminated products. . . . . The Clinton administration backed legislation to provide the USDA with the authority to demand meat recalls and impose civil fines on meatpackers. [But] Republicans in Congress failed to enact not only that bill, but also similar legislation [for four consecutive years.] . . . Under current law, the USDA cannot demand a recall [of contaminated meat.]" Can you fucking believe this? If a company decides voluntarily to recall contaminated meat, "it is under no legal obligation to inform the public—or even health officials—that a recall is taking place." Now, we don't mean to say that everyone working for the government is evil. Surely there are some decent, caring, moral, intelligent, well-intentioned people working for the FDA, EPA, USDA, and Bush administration. One former staff attorney-turned-environmentalist said the EPA "hasn't initiated one investigation in four years. They're not doing anything." See, she's a "good guy!" She finked on the EPA. Unfortunately, many of the "good guys" seem to be lost in the shuffle of politics and greed within these groups. So do yourself a favor and trust no one. Read ingredients. Ignore everything else. And, if you're totally incensed by what you've just learned, do something. Contact your representatives, senators, the President and Vice President and demand reform of these crooked, self-serving agencies. Go to www.congress.org to send a quick e-mail to these politicians. While you're at it, write a letter to the editor of your favorite magazine or newspaper, and ask others to join the crusade. Visit www.congress.org and click on "media guide" to access their contact information. Chapter 10 Don't Be a Pussy W hat if someone told you that you could totally change your life and have the body you want for the rest of your life? What if all you had to was follow a simple formula and maybe struggle for a month or two? What if you could reprogram your brain to actually enjoy healthy foods? Well, guess what? You _can_ change your life. You _can_ have the body you want for the rest of your life. You _can_ enjoy healthy foods. All you have to do is follow a simple formula, and be willing to delay gratification for a few months. A few months. That's it. Then you can enjoy a new body for the _rest of your life._ Don't be a pussy. You have all the nutritional information you need to become a Skinny Bitch. The rest is up to you. While this is a lifestyle, and not a diet, it is going to feel like a diet for the first thirty days or so. During this time, you will be retraining your brain, healing your taste buds, and cleansing and detoxifying your body. It might suck a little. Chances are, there will be times you feel deprived, angry, overwhelmed, and frustrated. But these few, fleeting moments will all be worthwhile once you are skinny. Truth be told, if you follow our guidelines, it won't be so bad. Before you even start making changes, take notice of how you feel and the role that your diet plays. Do you wake up tired? Is coffee the only thing that gets you going in the morning? Are you cranky in the afternoon? Do you need snacks to bolster your mood? Do you have little or no energy? Do you rely on soda or sugar for a little boost? Do you have trouble falling asleep? Is a glass of wine the only thing that gets you drowsy? When you eat something unhealthy, how do you feel while you're eating it? Right after? An hour later? How does it affect your sleep that night? How do you feel the next day? Pay attention to the negative effects your current diet and lifestyle have on your body, moods, and energy level. Feel free to start a little journal, writing what you eat and drink throughout the day and how you feel as a result. This way, when you start making positive changes to your diet, you'll appreciate _all_ of the results—not just the weight loss. Recognize that anything worth having is worth fighting for. Good health, vitality, more energy, more confidence, better sex, great abs, a tight ass—you either want 'em or you don't. You can continue plodding along in your life feeling like you're not living up to your glorious potential or you can dedicate yourself to creating the life you want. Fuck excuses about not having the time or the money. You spend forty hours a week working, or more if you're a full-time mom. Certainly your health and your body and _you_ are more important than anything else in your life. You are worthless to your colleagues, friends, and family if you do not value yourself enough to take excellent care of _you_. Yes, you have to put _yourself_ before your friends, parents, boyfriend, husband, and even your children. It won't make you a bad daughter or wife or mother; it will make you a less resentful, more confident, interesting, beautiful, patient, tolerant, and fun person to be around. Your bright, shining light will give everyone around you the permission and inspiration to shine more brightly. Love yourself enough to do whatever it takes to be the best _you_ you can be. An important part of any recovery program for addiction—and unhealthy eating is an addiction—is taking one day at a time. Don't torture yourself with thoughts of, "I can never eat steak again," or "How will I live without coffee?" Just take it one meal at a time. Don't think ahead with dread and anguish. One meal at a time. And when all feels hopeless, remember that you are in charge of what goes into your body, you don't answer to anyone, and you are _allowed_ to eat anything you want. Often just knowing we _can_ eat whatever we want is enough to keep us from eating whatever we want. We're so rebellious. If you feel really invigorated and motivated, and you're ready to completely immerse yourself in the Skinny Bitch lifestyle now, then rock on. Go for it. Otherwise, feel free to set mini-goals for yourself and tackle them one at a time. This means, spend the first week of your new life removing one dirty vice item. Whether it's cigarettes or coffee or alcohol or sugar or junk food or meat or dairy—just purge something negative from your life immediately. Choose something that you like and enjoy, but that you know you can let go of successfully. (But start right now. Don't let these intense feelings fade—use them.) Dedicate the week to getting this vice item out of your diet, your body, your kitchen, and your mind. Think of all you've learned about this item, and how disgusting it is. Envision the damaging effect it has on your organs, your mood, your health, and your appearance. Imagine exactly what it is that you'd be eating. Know how shitty you'd feel, physically and mentally, if you ate it. Understand that you have free will and that if you _wanted_ to eat it, you could. But know with every fiber and cell of your being that _today_ you wish to put only pure, beautiful, healthful foods in your body. Most important, acknowledge that no vice item will ever make you feel happy or whole or satisfied. In fact, all vice items make you _unhappy_ because they contribute to weight issues, health problems, mood swings, and low self-esteem. When you've got one week under your belt, feel great about what you've accomplished. Then, immediately, while continuing to steer clear of the item you banished in week one, start week two by ridding something else from your diet. Every week, until you've completely cleansed your life of poison and toxins, eliminate one more thing. Apply the same mindset, dedication, technique, and excitement you used in week one. Resign yourself to purifying your thoughts, body, and kitchen of this crappy vice item; realize you've just made your life better by not letting this vice item infect you anymore; gross yourself out thinking about what exactly it is and the effects it has on your body; think of how bad it makes you feel when you partake in it; and finally, remember that if you did _choose_ to eat/smoke/drink it, it wouldn't make you happy or fulfilled. Never feel like or say you are "giving up" your favorite foods. Those words have a negative connotation, like you are sacrificing something. You're not _giving up_ anything. You are simply empowered now and able to make educated, controlled choices about what you will and won't put into your body, your temple. Be grateful that you now know the truth about the foods you used to poison yourself with. Let all you think and speak of regarding this life change be positive. People who have positive attitudes are much more successful than those who don't. Be excited about feeling clean, pure, healthy, energized, happy, and skinny. Enjoy every second of this metamorphosis, knowing the journey is as important as the end result. Confucius never said, "A hungry woman is like a tornado of red ants and wildebeasts," but he should have. Because it's true. A hungry woman is a crazy woman, who will destroy everything in her path to be rid of the hunger. So you must always be prepared with healthy food on hand. Otherwise, seriously, you will fall off the wagon almost immediately. Your kitchen should be stocked at all times with the appropriate foods. Pack your lunch and a snack for school or work. Keep an emergency stash in your car, at your desk, and in your purse. Never, ever get caught with your pants down. Unfortunately, depending on where you live, restaurants may not be a safe place for the first month. The menu might not have any vegan or even vegetarian options, and it is easy to be hypnotized by the seductive smells of cooking. This doesn't mean you can't eat out ever again as long as you live. Just for thirty days. (Unless there are good veggie-friendly restaurants in your neighborhood.) You can't expect to change your life without a few minor adjustments. Your only priority for thirty days is to adhere to the regimen you're creating. Without straying. After you achieve thirty days of pure eating, you'll feel confident you have what it takes to get the job done. "I just survived thirty days. I'm so proud of myself. This is the healthiest I've ever been in my whole life. If I _want_ to, I can eat an old vice item. But why would I? I just made it thirty consecutive days. I'm going to keep going." If you test yourself before thirty days, you are setting yourself up for failure. Be patient and strong. When you reach the thirty-day milestone, don't run out and gorge yourself on crap. In fact, just keep doing what you've been doing. See and feel all the positive changes in your body, energy level, and self-esteem. Alcohol, cigarettes, coffee, and food are all addictive, physically and psychologically. Chances are, even after the thirty days, if you indulge in a vice item, you might go off the deep end. It is well known in Alcoholics Anonymous that you're only "one drink away from your next drunk." This means we think we can control our addictions. "I'll just have one drink. I'll just have pizza this one time. I'll just eat half a piece of cake." The truth of the matter is that we are powerless over our addictions. We don't want to make you feel like you can never eat your favorite foods ever again. We just want to impress upon you that it is very easy to obliterate all your progress with one bite, sip, or puff. Anyway, after one month of pure living, if you did eat the food you've been fantasizing about, you probably wouldn't even enjoy it. Really. You'd see that your brain has been tricking you and your taste buds all along. Now that your taste buds have healed and become more sensitized and your brain knows the truth, those old chemical, sugary, artificial, dead, rotting foods will taste "off" or "less than" somehow. If you do decide to partake in a vice item after thirty days, it cannot be out of weakness or for lack of preparation. You should never be somewhere and just say, "Fuck it." It should be a calculated, scheduled, premeditated choice. The portion should be decided on beforehand, should be smaller than you would normally have had, and served on a plate. (The package should be put away before you start eating.) Sit down at a table. Eat very slowly. Try not to finish the whole thing. Do not have another serving. Take note of how you feel while you're eating it, immediately after, an hour later, in bed that night, and the next day. Chances are, because your body is now pure, the vice item will make you feel a little nauseous, or headache-y, at the very least. And it most certainly won't taste as good as you imagine it will. Do not discount these negative feelings. They are your new, healthy, clean, pure organs speaking to you. Enough of all this melodrama. It's not like you're gonna be hungry and cranky for all of eternity. We know that dieters always "crash" when their favorite foods become forbidden. So we devised the Skinny Bitch plan to allow for cookies, cakes, chocolate, burgers, ice cream, etc. They just aren't the same ones you're used to. You're not giving up anything; you're just trading in all your old, gross food. Big deal. The new stuff is just as good. So don't kid yourself with the old "I had a craving" routine. Nobody's buying it. The only thing more annoying than the "Where do you get your protein?" question is the "My body is craving meat, I must need iron" comment. Most cravings are not reliable indicators of what your body needs. Smokers crave cigarettes, alcoholics crave alcohol, drug addicts crave drugs, and junk food eaters crave junk. If you eat shit for a few days, and you begin to crave a salad or a piece of fruit, that's a craving you can trust. Otherwise, it's just your addiction talking. Bitch-slap it, and get a hold of yourself. But feel free to try and understand your addiction first. In order for us to survive, our brains came equipped with dopamine, a pleasure-producing chemical. Dopamine is released during sex (or even just while flirting), so that we procreate and the human race won't die out. And food stimulates dopamine release so that we'll remember to eat and nourish our bodies. Basically, anything the brain perceives to be enjoyable will cause dopamine to lock onto brain cells and build a permanent memory trace of where pleasure comes from. Even though this evolved out of the need for survival, sometimes this can be a bad thing. Heroin, cocaine, alcohol, and nicotine all trigger the brain's pleasure circuitry. And not surprisingly, chocolate, sugar, and cheese also affect this same part of the brain. So you see, we can be _physiologically_ addicted to food. Any food can trigger the brain's pleasure center. Some of us are fortunate enough to experience dopamine ecstasy while eating broccoli, and we actually crave this healthy food. But the types of food and the degree of pleasure they bring will differ from one person to the next. The trick is resetting our memory traces to feel pleasure from healthy food, and no pleasure from junk food. Easier said than done. Especially for people who are addicted to cigarettes, alcohol, or drugs, or are overweight. Studies have shown that these people have fewer receptors for dopamine than other people. For them, the pleasure-giving chemical has fewer places to attach to brain cells, making it difficult for them to experience pleasurable feelings. So, because they aren't getting that "pleasure rush," they tend to smoke, drink, use drugs, gamble, or overeat. Now don't automatically diagnose yourself as one these people and assume you'll never get healthy. We are not at the mercy of our bodies. We are the commanders of our bodies. Unless we eat cheese. Cheese will rule our lives and fatten our asses if we don't kick the addiction. Cow's milk actually has traces of morphine in it! And for once, we can't blame factory farming. Morphine, along with codeine and other opiates, are naturally produced in cows' livers and end up in their milk. But that's not all. All milk, whether from a cow or a human, contains _casein,_ a protein that breaks apart during digestion and releases a whole slew of opiates. All these "feel good" chemicals exist so that newborns will nurse and thrive, and to ensure a bond between mothers and their young. Are you starting to get the picture? When a woman breastfeeds, her milk has an almost drug-like effect on the baby. The baby is totally hooked. He'll cry, not because he's hungry, but because he needs "a fix" of that pleasurable feeling produced by the opiates. Nature has guaranteed that our babies will nurse and grow. And when they reach a certain age, we wean them, and stop giving them these "drugs." And they're fine. But then we start them on cows' milk and an addiction is born. All dairy products contain casein, but cheese has the highest concentration. In fact, cheese contains far more casein than is naturally found in cows' milk. It also has phenylethylamine (PEA), an amphetamine-like chemical. So when we kid around and say, "I am addicted to cheese," it's not a joke—it's true. We are chemically addicted to cheese. Casein even finds its way into soy cheese. Whether manufacturers use it to up the protein content, to aide in melting, or because they know of its addictive quality, casein still has the same effect. So if you see casein on the list of ingredients, run! (Follow Your Heart's Vegan Gourmet cheeses are casein-free and totally vegan, so enjoy.) The following hormones and natural chemicals have all been identified in cows' milk: prolactin, somatostatin, melatonin, oxytocin, growth hormone, leuteinizing hormone-releasing hormone, thyrotropin-releasing hormone, thyroid-stimulating hormone, vasoactive intestinal peptide, calcitonin, parathyroid hormone, corticosteroids, estrogens, progesterone, insulin, epidermal growth factor, insulin-like growth factor, erythropoietin, bombesin, neurotensin, motilin, and cholecystokinin. If you think your will is strong enough to conquer all those mother-fuckers, you're on drugs! Dairy is fattening, and if you eat it, you'll never get skinny. You cannot control your addiction. You can't "just have one slice of pizza," or "only have cheese at parties." You're only one piece-of-cheese away from a total relapse. Eat the substitutes; they'll get you through. Thankfully, our bodies produce a few different chemical substances that help tame our appetites. One such hormone, leptin, is made by our fat cells. When fat cells in our bodies get adequate nourishment, they release leptin into the blood for two purposes. The first task at hand is alerting the brain to diminish the appetite. Next, our metabolism gets boosted, encouraging the body's cells to burn calories more quickly. Pretty cool, huh? Until we start "dieting." Typical low-calorie diets confuse the body into thinking it's starving. So our fat cells slow down their leptin production, to help _increase_ our appetites. Release the hounds! Now, we feel like we're starving! So we trash our diets and binge like rabid beasts. But diets high in fat don't fare any better. Fatty diets (think animal products) also lower leptin levels. You know where this is headed: Low-fat, plant-based diets actually boost leptin levels, helping each molecule of leptin to work more effectively. So help yourself succeed. Eating healthy foods like fruits, vegetables, whole grains, and beans will help curb your appetite and stimulate your metabolism. But when we have PMS, all bets are off. There's no telling when we'll cry, whom we'll kill, or what we'll eat. One culprit of mood swings and cravings is estrogen. Every month, our bodies produce extra estrogen in case of pregnancy. When we don't become preggers, estrogen levels plunge, triggering bloating, irritability, and cravings. The trick to avoiding these heinous feelings is maintaining balanced estrogen levels throughout the month. Like everything else, this can be done through diet. Fatty foods increase estrogen levels, while fibrous foods help reduce estrogen production. The _Journal of Obstetrics and Gynecology_ conducted a study exploring the effects of diet on menstrual symptoms. Women who eliminated animal fats from their diets experienced dramatic decreases of bloating and cravings. On average, menstrual cramps were reduced from four days to about two and a half days. Less cramps, cravings, and bloating! Those reasons alone are enough to swear off animal products. Even if you do have some serious PMS cravings, the good thing about the Skinny Bitch regimen is that there are plenty of naughty-tasting foods that you don't need to feel bad about. So eat all day long. As long as everything you put in your mouth meets Skinny Bitch approval, it's fine. Just be sure that when you're full, you _stop eating_. We know this is a foreign concept, but we're hoping it'll catch on. Imagine the actual size of your stomach (about the size of a one-quart container) or imagine what size you want it to be. There is no need to cram it full and stretch the shit out of it three times a day, every day, for your entire life. Look at the portion you put on your plate. Do you think it will fit in your stomach nicely, or that you'll need to force it in? Pare down. Just because you're "starving," you don't need to eat faster. When you're done eating, if you have the hiccups, indigestion, a stomachache, or you're burping and farting, that means you're eating too fast and gulping down air. Slow down. Breathe evenly. Conversely, make sure you aren't holding your breath while you speed-eat. It takes time for your brain to get the message that your stomach is full. The slower you eat, the less likely you are to overeat. Also, be sure to chew your food purposefully and slowly. Rest in between bites. Do not watch TV, read a magazine, talk on the phone, or do _anything else_ while you are eating. The goal is to know when you're full (without having _stuffed_ yourself) and be able to put the fork down. You aren't six anymore. You won't get the praise of elders for cleaning your plate. It's okay to leave food on your plate. But if you do still get off on scoring brownie points, you can earn extra credit by fasting. Yeah, fasting—willfully abstaining from food. For more than five thousand years, fasting has been used as a healthy method of weight loss. It is also a powerful tool for cleaning, flushing, detoxifying, and maintaining the body, and healing illnesses, both minor and major. When we eat, all of our body's energy goes toward digesting, using, and storing the food, and eliminating the waste. When we don't eat, all of our body's energy goes toward cleaning house. And with all the years of abuse, our house could sure use a cleaning. We absorb toxic chemicals from food, drinks, and the environment. Our body eliminates some of these through waste, but the rest remain as chemical by-products and free radicals (highly reactive chemicals that damage cells and contribute to premature aging, heart disease, and cancer). Fasting gets rid of these toxins. It also increases our blood's white cell count, which boosts immunity and protects us from disease. And because fasting is beneficial for the circulatory system, you can expect better skin, hair, and nails. Fasts can last anywhere from twenty-four hours to ten days or more. It's all up to you and how light, clean, and healthy you want to get. The longer the better, but even just one day one time a month is beneficial. There are too many types of fasts to cover them all, so we'll explain just a few. But it is imperative to really read up on fasting before diving in. A particular favorite is a raw or "live" food fast, when, obviously, you eat only raw foods for however many days you choose. This is a great beginner's fast, because you reap the benefits of fasting, while still being able to actually eat. It's also a good fast to do if you want to work your way up to a more stringent fast, like a juice fast, where the only thing you put in your body is fresh-pressed or fresh-squeezed juice (not pasteurized or packaged). Whether its fruit juice, veggie juice, or both, the enzymes are wonderful aides in the cleansing process. A liquid fast is similar to the juice fast, but includes soups, too (no beans or rice or chunks—just liquid). The alkalizing properties of the juices and soups help to neutralize the toxins being released from the body. For this and other reasons, the hardest fast is a water fast, where you have nothing but water. Don't be a competitive ass and launch yourself into this fast from the diet you exist on now. You've gotta learn to crawl before you can walk. Most people like to ease into a fast. They might eat smaller portions for a week prior. Or if they usually eat vegan junk food, they might abstain in preparation. We highly recommend eating as purely as possible leading up to a fast. (Meat-eaters should go vegetarian and then vegan before fasting.) It makes the transition more gradual and less jarring. Regardless of which fast you choose, be sure to drink a lot of water throughout. Your body will be detoxing like crazy, and you don't want to become dehydrated. All fasts are challenging, both physically and mentally. Do not expect it to be easy, especially at the beginning when you find yourself salivating over foods you don't normally even care about. But eventually, you get to a place where you are truly not hungry, and you feel light, clean, pure, and divine. When you do reintroduce food back into your diet, which should be done slowly with great care, you are almost repulsed by things you previously ate. It is quite beautiful to have such a new, fresh perspective. It is a real gift to see truths that weren't apparent before. Periodic repeated fasts are especially useful for this reason. They help our bodies and minds reestablish a new relationship with food. In fact, because of this, fasting can even be used to overcome addictions. When we eliminate the toxins that cause "cell memory cravings," we can eradicate the need for the food or drug that provided those toxins. Not surprisingly, some people experience headaches, weakness, nausea, cramping, stomach pains, sweating, a swollen tongue, bad breath, general aches and pains, increased temperature, or depression while fasting. Abstaining from food does not _cause_ these ailments. They are simply normal side effects of fasting. After two to three days of fasting, the body goes into autolysis, and actually starts digesting its own cells. With its wisdom, the body selectively decomposes the tissues and cells that are diseased, damaged, old, dead or in excess (fat). The body is literally digesting and expelling poisons, toxins, and bad cells that were already there—and it feels crappy. But this is actually a good thing, because the body is finally able to tackle some problems that were lurking within. During a fast, digestive enzymes are relieved from their usual role, and instead act to cleanse and rejuvenate the body. This rejuvenation process includes the production of new cells. And when more cells are being produced than are dying, the aging process is actually being reversed. This phenomenon occurs during juice and water fasts. Eventually, you'll notice sharper senses of smell, sight, sound, and taste. You'll feel lighter physically, mentally, and emotionally. All magic aside, fasting is _not_ for you if you're pregnant, lactating, underweight, or suffering from severe wasting diseases, such as neurological degenerative diseases and certain cancers. Diabetics and people suffering from hypoglycemia can fast, but only with medical supervision. For that matter, anyone with any medical condition should consult a doctor before fasting. # Vitamins Vitamins are an integral part of a healthy lifestyle. Here are some significant vitamins and minerals, a description of why they're important, and which foods provide them: Calcium strengthens bones, provides for healthy teeth, reduces risk of colon cancer, decreases chances of bone loss, aids the nervous system, and alleviates insomnia. Eat almonds, Brazil nuts, seeds, nuts, soybeans, kale, collard greens, broccoli, kelp, and molasses to get calcium. Folic acid promotes healthy skin, protects against parasites and food poisoning, helps ward off anemia, and fights against birth defects. To get folic acid, eat leafy green veggies, carrots, artichokes, fruit, cantaloupe, avocados, apricots, beans, lentils, soybeans, garbanzos, barley, and whole wheat. Iron aids growth, promotes resistance to disease, prevents fatigue and anemia, and enhances good skin tone. It can be found in nuts, pumpkin seeds, beans, lentils, whole grains, oatmeal, asparagus, molasses, broccoli, spinach, bok choy, peas, swiss chard, green beans, and sea veggies. Magnesium (known as the anti-stress mineral) fights depression, boosts energy, helps burn fat, prevents heart attacks, maintains good cholesterol levels, aids indigestion, combats PMS symptoms, helps prevent premature labor, and keeps teeth strong and healthy. When combined with calcium, it works as a natural tranquilizer. Eat nuts, seeds, sunflower seeds, green vegetables, soybeans, kelp (seaweed), and molasses to get a good dose, especially if you're on The Pill. Omega-3 fatty acids fight heart disease, lower bad cholesterol levels, lessen the likelihood of blood clots, reduce the risk of breast cancer, help with rheumatoid arthritis, and keep skin, hair, and nails healthy. Sources for these fatty acids are flaxseeds, walnuts, pumpkin seeds, hempseed oil, and other seeds and their unrefined oils. Omega-6 fatty acids combat PMS, ward off acne, eczema, and psoriasis, and help with endometriosis and rheumatoid arthritis. Flaxseed oil, evening primrose oil, borage oil, and black currant seed oil are all good sources. Potassium aids in reducing blood pressure, increases clear thinking by helping send oxygen to the brain, and helps the body dispose of waste. It's found in bananas, citrus fruits, cantaloupe, tomatoes, watercress, green leafy vegetables, sunflower seeds, avocados, lentils, potatoes, and whole grains. The B Vitamins improve mental attitude, aid in digestion, help migraine headaches, contribute to healthy skin, act as natural diuretics, strengthen immunity, increase energy, improve concentration and memory, and are good for the nervous system. Eat whole wheat, wheat germ, bran, oatmeal, whole grains, brown rice, beans, nuts, seeds, soybeans, lentils, dates, figs, bananas, and vegetables. Vitamin C accelerates healing, lowers blood pressure, prevents colds, protects against cancer, and helps decrease blood cholesterol. It also forms collagen, which is important for growth the and repair tissue cells, blood vessels, gums, bones, and teeth. Vitamin C is especially important for women who smoke or take birth control pills. It's easy to get vitamin C by eating broccoli, brussel sprouts, cabbage, collard greens, green peppers, spinach, watercress, potatoes, grapefruits, oranges, and papayas. Vitamin D, in conjunction with calcium and phosphorous, helps build strong bones and teeth. Not only does vitamin D help our bodies assimilate vitamin A, but it also prevents colds when teamed up with vitamins A and C. All you need to do to obtain vitamin D is get direct sun exposure on your skin. Vitamin E keeps you looking younger, inhibits cancer cell growth, fights fatigue, prevents blood clots, lowers blood pressure, decreases the risk of Alzheimer's disease, and accelerates the healing of burns. It's found in wheat germ, whole grain cereals, whole wheat, nuts, sunflower seeds, leafy greens, and vegetable oils. Zinc helps with infertility issues, is important for brain function, maintains the body's acid/alkaline balance, aids in collagen formation, and helps form insulin (needed for many vital enzymes). Foods with high concentrations of zinc are wheat germ, whole grains, pumpkin seeds, sesame seeds, and soybeans. When we eat properly, we can get almost all of the nutrients we need from food sources. However, Vitamin B-12 is only found in animal products, so most vegans and vegetarians take B-12 supplements. Sublingual liquid B vitamins with folic acid are more easily and quickly absorbed than pills. If you are concerned that you aren't getting sufficient vitamins in your diet and wish to take supplements, consult a holistic physician. Chapter 11 Let's Eat W e set out to write this book for a few reasons: • We could not tolerate the cruelty associated with a meat-eating diet and we wanted to help end animal suffering. • We couldn't bear to have "real" jobs. • We wanted to change peoples' lives. We _truly_ want to help you succeed and make this all as easy as possible. In this chapter, we've compiled a few lists so that there will be no confusion as to what you should or shouldn't eat. After reading the whole book, if you're feeling uncertain about what to buy or order, just whip out your little _Skinny Bitch_ and come right to this chapter. There will be no doubt that you're making the right food choices. Breakfast is the most important meal of the day. But not why you think. The cereal and dairy industries lead us to believe that without a big, "healthy" breakfast, we won't have enough energy to get us through the day. But Sugar Smacks with cow's milk hardly constitutes a healthy, viable energy source. The _real_ reason breakfast is so important is that it sets the tone for your entire day of eating. If you eat a shitty breakfast, you will likely crave (and eat) crap all day. And, if you eat too early in the morning, you'll be interrupting your body's cleaning session. Remember, when your body isn't working on food, it's working on you! When your "cleaning crew" is in the middle of cleanup, and you start cramming food in, "they" get overwhelmed. They stop what they're doing, throw their hands up, scratch their heads, and finally, decide that they just can't deal with this mess you're making. So they opt to store it away as fat and pretend they'll get to it later. So when you wake up, you should wait to eat breakfast until you're truly hungry. Don't just eat right away because that's what you're used to. After a few days, you'll grow to love that empty feeling in your stomach and know that the initial headaches, nausea, and hunger were just your body's cleaning crew. Feel free to enjoy a cup of caffeine-free, organic, herbal tea upon waking. But other than that, the best thing to do is wait until you're really hungry. When you do eat, the breakfast of skinny bitches is organic fruit. This may seem light in comparison to your previous bagel or eggs or cereal. But again, once you adapt, you will be totally fulfilled by fruit. Eat one piece (or serving) slowly. After a period of time—perhaps ten minutes or so—when you feel hungry, eat another piece, slowly. When you feel hungry again, eat one more. Breakfast is over. # Breakfast Food List We hope you'll at least try having just fruit for breakfast before deciding it's not for you. But if you give it a go, and after two weeks you still feel angry and violent just thinking about it, consult our list of acceptable breakfast foods:(R) found in refrigerator section, (F) found in freezer section Arrowhead Mills: organic blue corn pancake and waffle mix Arrowhead Mills: organic whole grain pancake and waffle mix Food For Life: Ezekiel 4:9 cereal Barbara's Bakery: Puffins cereal Barbara's Bakery: Shredded Spoonfuls cereal Peace Cereal: vanilla almond crisp Peace Cereal: maple pecan crisp Nature's Path: Optimum Slim cereal Nature's Path: Optimum Power Breakfast cereal Health Valley: organic raisin bran flakes Health Valley: organic oat bran flakes with raisins Old Wessex Ltd.: Irish-style oatmeal Old Wessex Ltd.: 5-grain cereal Nature's Path: organic instant hot maple nut oatmeal Ancient Harvest: organic quinoa flakes Rice Dream: original enriched rice milk Original EdenSoy: organic soymilk Original EdenBlend: rice & soy beverage House: tofu steak (R) Whole Soy & Co.: creamy cultured soy (yogurt) (R) Silk: cultured soy (yogurt) (R) Amy's: organic tofu scramble (F) Van's: all natural organic original waffles (F) Lifestream: Mesa Sunrise toaster waffles (F) French Meadow Bakery: men's bread French Meadow Bakery: healthy hemp sprouted bread French Meadow Bakery: brown rice bread Nature's Path: organic Manna breads (F) Fabe's All Natural Bakery: vegan muffins (F) Zen Bakery: muffins (R) Zen Bakery: cinnamon raisin rolls (R) Whole Foods: organic English muffins (R) Food For Life: Ezekiel 4:9 sprouted grain bagels (F) Tofutti: Better Than Cream Cheese (R) (the kind _without_ hydro-genated oils.) Lightlife: Smart Bacon (R) Lightlife: Gimme Lean! sausage style (R) Organic Fruit: (Earlier, we mentioned the benefit of eating just fruit for breakfast. But here, we did include other breakfast foods. It is up to you to decide how diligent you want to be with your diet. We just wanted to provide hearty breakfast choices should you disregard the fruit-by-itself theory. Totally your choice. You can eat the fruit before eating the muffin or pancakes or waffles. Whatever you want.) # Lunch Food List Don't eat lunch until you're close to ravenous. This will allow your breakfast to pass through your body without having food piled on top of it. In a perfect, skinny world, lunch consists of a fresh, organic salad with lots of raw vegetables. But if that's too boring or stringent for you, feel free to choose something else from our yummy lunch list: Food For Life: Ezekiel 4:9 bread (F) (or bakery/bread aisle) Arrowhead Mills: organic Valencia peanut butter MaraNatha: organic raw almond butter I.M. Healthy: SoyNut butter Bionaturae: organic fruit spreads Natural Touch: Tuno (faux tuna) Morningstar Farms: Tuno Amy's: All American burger (F) Amy's: California burger (F) Amy's: Texas burger (F) Gardenburger's: flame-grilled burgers (F) Gardenburger's: flame-grilled chik'n (F) Whole Foods Bakehouse: organic burger buns Tofurkey: deli slices Yves: veggie bologna (R) Yves: veggie turkey (R) Yves: veggie salami (R) Follow Your Heart: Vegan Gourmet cheese alternative (R) Earthbound Farm: organic salad greens (R) Fantastic Foods: tabouli Fantastic Foods: organic whole wheat couscous Fantastic Carb 'Tastic Soup: vegetarian chicken gumbo Fantastic Carb 'Tastic Soup: shiitake mushroom Fantastic Big Soup: five bean Fantastic Big Soup: country lentil Amy's Organic Soups: black bean vegetable Amy's Organic Soups: butternut squash Amy's Organic Soups: lentil vegetable Amy's Organic Soups: chunky vegetable Amy's: organic chili Health Valley: organic split pea soup Health Valley: organic lentil soup Health Valley: organic black bean soup Imagine: organic vegetable broth Imagine: organic no-chicken broth Pacific: organic vegetable broth organic vegetables # Dinner Food List When you're feeling really hungry, it's time for din-din. Dinner is easy and fun. Just pick from the list, or create your own healthy vegan fest: Health Best 100% Organic: red lentils Health Best 100% Organic: green lentils Health Best 100% Organic: barley Health Best 100% Organic: split peas Health Best 100% Organic: amaranth Arrowhead Mills: organic whole millet Lundberg Family Farms: organic short grain brown rice Lundberg Family Farms: organic brown rice pasta DeBoles: organic whole wheat pasta Ancient Harvest: organic quinoa supergrain pasta Eddie's Spaghetti: organic vegetable pasta Pastariso: organic brown rice fettuccine Pastariso: organic brown rice elbow macaroni Rising Moon Organics: spinach Florentine ravioli with tofu (F) Chef Nikola's Kitchen: roasted eggplant in herbed balsamic sauce (F) Amy's Organic: Asian noodle stir-fry (F) Amy's Organic: Thai stir-fry (F) Amy's: roasted vegetable pizza (no cheese) (F) Nate's: meatless meatballs (F) Health is Wealth: buffalo wings (F) Health is Wealth: chicken-free patties (F) Health is Wealth: chicken-free nuggets (F) Tofurkey: _Tofurkey_ dinner (F) Gloria's Kitchen: assorted vegan prepared entrees (F) Lightlife: organic tempeh (R) Lightlife: _Smart Ground_ (ground "meat") (F) Nasoya: organic tofu (R) White Wave: chicken-style seitan (R) Lightlife: _Smart Dogs_ (R) Yves: veggie dogs (R) Rudi's Organic Bakery: white hot dog rolls Now & Zen: _UnChicken_ (R) Now & Zen: _UnSteak_ (R) Yves: _Veggie Ground Round Mexican_ (Mexican-style ground "meat") (F) Bearitos: taco shells Garden of Eatin': blue corn taco shells Alvarado St. Bakery: organic sprouted wheat tortillas organic vegetables Obviously, the foods on the lunch and dinner lists can be used interchangeably. A helpful hint: Prepare large batches of staple food items on Sunday night, to tide you over for your busy workweek. Brown rice, lentils, homemade hummus, soups, and pastas are all good candidates. But try not to do this with your veggies because they'll lose some of their enzymatic punch. # Acceptable Junk Food, Snacks & Desserts There's something about a snack that makes you feel like a kid again. And that's a good thing. If you're hungry, but not quite ready for dinner, have a small snack. As long as it's healthy, it doesn't spoil your dinner, and you only have a small serving, there is no reason to feel bad about having a snickety-snack. But don't have one just because you can. Only eat it if you want it. Otherwise, just wait for dinner. Dessert is one of God's many gifts to humans. Indulge. Like snacks, if your desserts are healthy and eaten in controlled portions, enjoy them without the guilt! 365: organic chocolate soymilk Whole Foods: organic date coconut rolls Barbara's Bakery: organic graham crackers Dagoba: organic dark chocolate bars Uncle Eddie's: vegan cookies Organica Foods: vegan cookies Fabe's All Natural Bakery: vegan cookies Newman's Own: organic Fig Newmans Laura's Wholesome Junk Food: _Bitelettes_ (cookies) Nutrilicious Natural Bakery: donut holes MI-DEL: vanilla snaps Country Choice: certified organic sandwich cremes Back to Nature: classic creme sandwich cookies Back to Nature: chocolate & mint creme sandwich cookies Chocolove: Belgian dark chocolate Endangered Species: dark chocolate bars Tropical Source: rice crisp dark chocolate Ecco Bella: _Health By Chocolate_ Raw Balance: _Carobelles_ (www.rawbalance.com) Gertrude & Bronner's Magic: _Alpsnack_ LäraBar: all flavors Terra: exotic vegetable chips original Terra: spiced sweet potato chips Maine Coast Sea Vegetables: sea chips Garden of Eatin': _Sunny Blues_ (tortilla chips with sunflower seeds) Guiltless Gourmet: yellow corn baked chips Kettle Organic Tortilla Chips: sesame blue moons Veggie Stix: shoestring potato sticks Robert's American Gourmet: _Tings_ Robert's American Gourmet: _Spicy Tings_ Robert's American Gourmet: _Veggie Booty_ Newman's Own: organic salted round pretzels Koyo Organic Rice Cakes: dulse Koyo Organic Rice Cakes: mixed grain Nature's Path: tamari flax crackers Back to Nature: classic rounds Soy Dream: non-dairy frozen desserts (F) Soy Delicious: non-dairy frozen desserts (F) Double Rainbow Soy Cream: non-dairy desserts (F) Soy Delicious: _Li'l Buddies_ ("ice cream" sandwiches) (F) Sweet Nothings: non-dairy fudge bars (F) # Condiments, Baking Supplies & Miscellaneous Don't worry about the little odds and ends. We've thought of everything. Earth Balance: natural buttery spread (R) Soy Garden: natural buttery spread (R) Follow Your Heart: _Vegenaise_ (mayonnaise substitute) (R) Nasoya: _Nayonaise_ Muir Glen: organic ketchup Westbrae: natural ketchup Whole Kids: organic yellow mustard Spectrum Naturals: organic sesame oil Spectrum Naturals: organic canola oil Spectrum Naturals: organic extra virgin olive oil MaraNatha: organic raw tahini Bragg Liquid Aminos: all purpose seasoning (soy sauce substitute) Sea Seasonings: organic kelp granules with cayenne Annie's Naturals: goddess dressing OrganicVille: sesame tamari organic vinaigrette The Wizard's: organic original vegetarian Worcestershire sauce Essential Living Foods: organic agave nectar or syrup Shady Maple Farms: certified organic pure maple syrup Sugar in the Raw: Turbinado sugar from natural cane Florida Crystals: organic cane sugar Wholesome Sweeteners: organic sucanat Hain Pure Foods: organic brown sugar Stevita Company Inc.: stevia spoonable Dr. Oetker Organics: chocolate cake mix Dr. Oetker Organics: vanilla cake mix Dr. Oetker Organics: chocolate icing mix Dr. Oetker Organics: vanilla icing mix Dr. Oetker Organics: chocolate chip cookie mix Ener-G: egg replacer Chatfield's Carob & Compliments: dairy-free carob morsels Sunspire: grain-sweetened chocolate chips Arrowhead Mills: organic oat flour Arrowhead Mills: organic whole wheat flour Arrowhead Mills: organic spelt flour Arrowhead Mills: organic brown rice flour Arrowhead Mills: organic blue corn meal Arrowhead Mills: organic yellow corn meal Arrowhead Mills: organic flax seeds When crafting your own day of eating from the food lists provided, use your head. Create a well-balanced menu for the day without being repetitive. For example, don't eat pancakes for breakfast, a sandwich for lunch, and a soy burger for dinner. That would be eating all bread, but no fruits or veggies. Duh. Use your head. Try to always think in terms of fruits, veggies, whole grains, soy, and legumes for a well-balanced day of eating. If you need a little more guidance, feast your eyes on this, a month's worth of menus: # Week One Monday Breakfast: Mango, banana, kiwi and soy yogurt. Lunch: Spinach salad with shredded carrots, chopped almonds, red onion, fresh garlic, cubed tofu, and sesame oil. Dinner: Pasta with zucchini, tomatoes, garlic, fresh parsley, pine nuts, and olive oil. Tuesday Breakfast: Fresh squeezed orange juice, whole grain muffin with soy butter, banana, and strawberries. Lunch: Tabouli salad with marinated tofu, eggplant, and red peppers. Dinner: Veggie nachos! Corn chips with veggie chili, soy cheese, guacamole, scallions, and tomatoes. Wednesday Breakfast: Fresh squeezed grapefruit juice and slow-cooking oatmeal with blueberries, strawberries, and raspberries. Lunch: Veggie burger on whole grain bun with red onion, lettuce, tomato, avocado, and alfalfa sprouts. Served with vegan potato salad. Dinner: Fake chicken patty with brown rice, lentils, and steamed kale. Thursday Breakfast: Fresh squeezed OJ, whole grain bagel with vegan cream cheese, sliced tomatoes, and red onion. Lunch: Soup and salad. Dinner: Veggie stir-fry with peppers, onions, garlic, carrots, bok choy, and mushrooms served with brown rice and tofu. Friday Breakfast: Granola with sliced banana, peaches, and blueberries with soy yogurt. Lunch: Club sandwich with fake bacon, fake turkey slices, avocado, lettuce, tomato, sprouts, and Vegenaise (fake mayo). Served with three-bean salad. Dinner: Take out from your favorite Thai restaurant: vegan Pad Thai, emphasizing no egg or shrimp or fish stock. Saturday Breakfast: Fresh squeezed OJ, blue corn and blueberry pancakes served with fresh strawberries. Lunch: Salad with shredded carrots, couscous, cranberries, and walnuts, dressed with citrus vinaigrette. Served with lentil soup. Dinner: Veggie fajitas with sautéed peppers, onions, mushrooms, and fake chicken strips, topped with fresh Pico de Gallo. Sunday Breakfast : Fresh squeezed OJ and tofu scramble with zucchini, peppers, onions, garlic, spinach, and kale served with whole grain toast. Lunch: Lentil salad with asparagus tips and walnuts in a raspberry vinaigrette. Served with an entire steamed artichoke and a vegan lemon-butter dipping sauce. Dinner: No-cheese or vegan-cheese pizza loaded with veggies! # Week Two Monday Breakfast: Fruit smoothie with a splash of OJ and fresh banana, frozen pineapple, and coconut. Lunch: All-American salad with romaine lettuce, corn, peas, and BBQ tofu cubes in a vegan ranch dressing. Dinner: Italian night! Your favorite pasta and tomato sauce with fake meatballs and whole grain garlic bread. Tuesday Breakfast: Fresh squeezed OJ, cereal with soy or rice milk, served with blueberries, sliced banana, and strawberries. Lunch: Veggie chili with corn bread! Dinner: Mashed potatoes, Gardenburger Meatless Riblets, and sautéed collard greens and Swiss chard. Wednesday Breakfast: Fresh squeezed OJ and toaster waffles with sliced strawberries, bananas, and peaches. Lunch: Vegan Caesar salad with fake chicken chunks. Dinner: Brown rice and lentils with steamed broccoli and red cabbage. Thursday Breakfast : A shitload of cantaloupe. Lunch: Fake deli meats on whole grain bread with lettuce and tomato and a side of Asian cole slaw (shredded carrots, red cabbage, green cabbage, rice vinegar, sesame oil, and sesame seeds). Dinner: Fake meatloaf served with corn on the cob, peas, and sautéed spinach and garlic. Friday Breakfast: Smoothie time with a splash of apple juice and peaches, blueberries, raspberries, and a dash of flaxseed oil (or a tablespoon of ground flaxseeds). Lunch: Japanese lunch of avocado rolls, miso soup, and a small salad. Dinner: Veggie burger with sautéed mushrooms, onions, soy cheese, lettuce, and tomato served with baked French "fries." Saturday Breakfast: Fresh squeezed OJ and vegan French toast with blueberries, strawberries, and banana. Lunch: Mixed greens with hearts of palm, sun-dried tomatoes, yellow tomatoes, asparagus, basil, garlic, and pine nuts in an oil and vinegar dressing. Dinner: Veggie dog loaded with veggie chili and soy cheese, served with vegan potato salad. Sunday Breakfast: Fresh squeezed OJ and a fake egg sandwich (using House Tofu Steak extra-firm tofu, sliced and pan fried, with fake bacon and soy cheese on a whole grain bagel with soy butter, salt, pepper, and ketchup). Lunch: Split pea soup and a mixed greens salad. Dinner: Penne with butternut squash and raw pesto (pine nuts, basil, garlic, olive oil). # Week Three Monday Breakfast: Fresh squeezed OJ and slow-cooking oatmeal with apples, cinnamon, and pecans. Lunch: Whole-wheat vegetable wrap with sautéed eggplant, portabella mushroom, and roasted red peppers served with a small side salad. Dinner: Veggie stir-fry with green peppers, carrots, zucchini, tofu, bok choy, onions, and garlic served with brown rice. Tuesday Breakfast: A big-ass hunk of honeydew melon. Lunch: Salad greens with red onion, cherry tomatoes, black beans, and corn, served with a baked sweet potato. Dinner: Baked Teriyaki tofu with brown jasmine rice and steamed green beans. Wednesday Breakfast : Fresh- pressed apple juice and a whole grain bagel with peanut butter, jelly (organic and sugar-free, of course), and sliced banana. Lunch: Mediterranean platter with hummus, eggplant, grape leaves, falafel, peppers, olives, and tomatoes. Dinner: Veggie burrito with pinto beans, brown rice, guacamole, soy cheese, lettuce, tomato, and salsa. Thursday Breakfast: Granola with bananas, blueberries, strawberries, and soy or rice milk. Lunch: Portabella mushroom burger with arugula and caramelized onions, served with an avocado-tomato salad. Dinner: Veggie lasagna with red sauce, your favorite veggies, fake ground meat, and tofu ricotta (in food processor, blend firm tofu, garlic, salt, small amount of olive oil, and dried oregano). Friday Breakfast: Fruit salad—go crazy! Lunch: Fake tuna (Tuno with accents of shredded carrots, chopped onion, diced celery, and Vegenaise) on whole grain bread served with a handful of baked corn chips. Dinner: Steamed broccoli, carrots, kale, red cabbage, cauliflower, and tofu with brown rice, drizzled with sesame oil and sea salt. Saturday Breakfast: Ranchos-fake-Huevos wrap with scrambled tofu, sautéed onions and peppers, black beans, avocado, and salsa in a corn tortilla. Lunch: Chinese fake chicken salad with snow peas, cabbage, carrots, mandarin oranges, fake chicken chunks, and cashews. Dinner: Seitan (wheat-meat) with steamed leeks, white beans, and garlic-roasted potatoes. Sunday Breakfast: Fresh squeezed OJ and apple cinnamon pancakes with raspberries and bananas. Lunch: Fake bacon, lettuce, tomato, and avocado on whole grain bread with leftover roasted potatoes from last night's dinner. Dinner: Veggie shish kabobs with green peppers, red peppers, mushrooms, onions, cherry tomatoes, and Gardenburger Meatless Riblets, served with corn on the cob. # Week Four Monday Breakfast: Fruit smoothie with peaches, banana, and strawberries and a splash of soy or rice milk. Lunch: Chef's salad with mixed greens, carrots, tomatoes, vegan cheese, and assorted chopped fake deli meats. Dinner: Fake steak with a baked sweet potato, lentils, and steamed kale. Tuesday Breakfast: Fresh-squeezed OJ and toaster waffles with banana, strawberries, and blueberries. Lunch: Veggie minestrone soup with a small side salad. Dinner: Veggie dog smothered in veggie chili, served with collard greens. Wednesday Breakfast: Fresh-pressed apple juice and slow-cooked oatmeal with dates, raisins, walnuts, and bananas. Lunch: Grilled soy cheese with tomato and a small side salad. Dinner: Shepherd's pie with vegan mashed potatoes, fake ground meat, lentils, corn, and sautèed spinach and mushrooms. Thursday Breakfast: Fresh-squeezed OJ, an entire grapefruit, and a whole grain muffin. Lunch: Veggie chili with an avocado-tomato salad and a handful of baked corn chips. Dinner: Fusilli with zucchini, olives, basil, tomato, garlic, and olive oil served with whole grain Italian bread. Friday Breakfast: Fresh-squeezed OJ and cereal with peaches, banana, blackberries, and soymilk. Lunch: Cucumber and avocado roll with miso soup and a small salad. Dinner: No-cheese or vegan-cheese pizza loaded with veggies! Saturday Breakfast : Fake egg sandwich. Lunch: Fake chicken Caesar salad. Dinner: Steamed cauliflower, broccoli, carrots, and red cabbage over brown rice. Sunday Breakfast: Create your own fruit smoothie! Lunch: Veggie burger with sautèed mushrooms, avocado, lettuce, tomato, onion, and sprouts served with roasted potato wedges. Dinner: Fake chicken patty with BBQ sauce, black-eyed peas, collard greens, and corn on the cob. Feel free to snack on a handful of raw organic nuts each day. If you really want to treat yourself right, have fresh-pressed veggie juice every day. (Fresh-pressed, not packaged or pasteurized.) Don't forget to include organic, caffeine-free teas and to drink eight glasses of water a day. We include a list of recommended cookbooks toward the end of the book. Either buy a book or use the Internet for easy vegan recipes. One great site, veganpeace.com, includes recipes and a review of veggie cookbooks. Another winner is VegCooking.com. Feeling gutsy and wanna branch out on your own? Go for it—shop 'till you drop. Here are ingredient lists of unfamiliar terms to help with your grocery outings. (Please be warned, this section is boring.) # Bad or Potentially Bad Ingredients* Alanine or amino acids: The building blocks of protein in all animals and plants. Make sure they are plant derived. Albumen or albumin: Found in eggs, milk, muscles, blood, and many vegetable tissues and fluids. May cause allergic reaction. In cakes, cookies, candies, and some wines. Ambergris: From whale intestines. Used as a flavoring in foods and beverages. Aminosuccinate Acid or aspartic acid: Can be animal or plant source (e.g., molasses). Arachidyl proprionate: A wax that can be from animal fat. Alternatives are peanut or vegetable oil. Artificial Color, FD &C food color: Derived from coal-tar. Can contain trace amounts of lead and arsenic. Potentially carcinogenic. Alternatives: coloring from grapes, beets, turmeric, saffron, carrots, chlorophyll, annatto, alkanet. Beta carotene, provitamin A: A pigment found in many animal tissues and in all plants. Used in the manufacturing of Vitamin A. Make sure it is derived from plant sources. Bo ne meal: Crushed or ground animal bones. In some vitamins and supplements as a source of calcium. Butylated Hhydroxyanisole (BHA), butylated hydroxytoluene (BHT): An antioxidant and/or preservative commonly found in baked goods, canned items, powdered soups, bacon, foods containing artificial colors or flavors. Can cause cancer, birth defects, and infertility. Carmine, cochineal, carminic acid: Red pigment from the crushed female cochineal insect. Reportedly, 70,000 beetles must be killed to produce one pound of this red dye. Used in red applesauce, and other foods (including red lollipops and food coloring). May cause allergic reaction. Casein, caseinate, sodium caseinate: Milk protein found in dairy products, as well as "non-dairy" creamers, and soy cheese. Cysteine, L-form : An amino acid from hair, which can come from animals. Used in some bakery products. Cystine: An amino acid found in urine and horsehair. Used as a nutritional supplement. Duodenum substances: From the digestive tracts of cows and pigs. Added to some vitamin tablets. Fatty acids: Can be one or any mixture of liquid and solid acids such as caprylic, lauric, myristic, oleic, palmitic, and stearic. Alternatives: vegetable-derived acids, soy lecithin. Fish liver oil: Used in vitamins, supplements, and milk fortified with vitamin D. Alternative: yeast extract ergosterol. Gelatin, gel: Protein obtained by boiling skin, tendons, ligaments, and/or bones with water. From cows and pigs. Used as a thickener for fruit gelatins and puddings and in vitamins as a coating and as capsules. In candies, marshmallows, cakes, ice cream, yogurts. Sometimes used to assist in "clearing" wines. Alternatives: carrageen (carrageenan, Irish moss), seaweeds (algin, agar-agar, kelp), pectin from fruits, dextrins, locust bean gum, cotton gum. Glycerin, glycerol : A byproduct of soap manufacturing (normally uses animal fat). In foods, mouthwashes, chewing gum, toothpastes. Derivatives: Glycerides, Glyceryls, Glycrethglycreth-26, Polyglycerol. Alternatives: vegetable glycerin—a byproduct of vegetable oil soap, derivatives of seaweed. Isinglass: A form of gelatin prepared from the internal membranes of fish bladders. Sometimes used in "clearing" wines and in foods. Alternatives: bentonite clay, "Japanese isinglass," agar-agar. (See alternatives to Gelatin). Lactic acid: Found in blood and muscle tissue. Also in sour milk, beer, sauerkraut, pickles, and other food products made by bacterial fermentation. Alternative: lactic acid from beets, plant-milk sugars. Lactose: Milk sugar from milk of mammals. In foods, tablets, baked goods. Alternatives: plant-milk sugars. Lard: Fat from hog abdomens. In baked goods, French fries, refried beans. Alternatives: pure vegetable fats or oils. Lecithin or choline bitartrate: Waxy substance in nervous tissue of all living organisms, but frequently obtained for commercial purposes from eggs and soybeans. Also from blood or milk. Alternatives: soybean lecithin or corn-derived. Lipase: Enzyme from the stomachs and tongue glands of calves, baby goats, and lambs. Used in cheese-making and in digestive aids. Alternatives: vegetable enzymes, castor beans. Lipoids, lipids: Fat and fat-like substances that are found in animals and plants. Alternatives: vegetable oils. Marine oil: From fish or marine mammals (including porpoises). Used as a shortening, especially in some margarines. Alternatives: vegetable oils. Methionine: Essential amino acid found in various proteins (usually from egg albumen and casein). Used for freshness in potato chips. Monoglycerides, glycerides, (See Glycerin): From animal fat. In margarines, cake mixes, candies, foods, etc. Alternative: vegetable glycerides. Monosodium glutamate (MSG): Flavor enhancer blamed for reproductive, nervous system, and brain disorders. Found in soups, sauces, gravies, and sometimes hidden in baby food, baby formula, low-fat and no-fat milk, candy, gum, processed foods, and applied to non-organic fruits and vegetables as a wax or pesticide. Myristal, ether sulfate, myristic acid: Organic acid in most animal and vegetable fats. In butter acids and food flavorings. Derivatives: isopropyl myristate, myristal ether sulfate, myristyls, oleyl myristate. Alternatives: nut butters, oil of lovage, coconut oil, extract from seed kernels of nutmeg, etc. "Natural sources": Can mean animal or vegetable sources. Most often in the health food industry (especially in the cosmetics area), it means animal sources, such as animal elastin, glands, fat, protein, and oil. Alternatives: plant sources. Nitrates: Potentially deadly, carcinogenic preservatives. Found in processed foods and meats. Nucleic acids: In the nucleus of all living cells. Used in vitamins, supplements. Alternatives: plant sources. Oleic acid: Obtained from various animal and vegetable fats and oils. Usually obtained commercially from inedible tallow. (See Tallow.) Alternatives: coconut oil. Olestra: A fat substitute found in low fat and dairy-type products that reduces fat-soluble vitamins in the body. Panthenol, dexpanthenol, vitamin B-Complex complex factor, provitamin B-5: Can come from animal, plant, or synthetic sources, so be sure to buy only plant-based. Pepsin: In hogs' stomachs. A clotting agent. In some cheeses and vitamins. Same uses and alternatives as Rennet. (see Rennet) Polysorbates: Derivatives of fatty acids. Potassium bisulfite, sodium bisulfite, sulfur dioxide: Used as anti-fungal, anti-browning, or antioxidant in cheeses, processed meats, canned fruits and vegetables, dried fruits, and/or baked goods. Can cause asthma, shock, or death. Potassium bromate: Found in baked goods, can cause cancer and kidney and nervous system disorders. Banned worldwide except Japan and U.S. Rapeseed Oil: An emulsifier and stabilizer found in baked goods, dairy products, processed meats. Can cause cancer, heart disease, vision loss. Rennet, rennin: Enzyme from calves' stomachs. Used in cheese-making and in many coagulated dairy products. Alternatives: lemon juice or vegetable rennet. Saccharine: Artificial sweetener found to cause cancer. Stearic acid: Fat from cows and sheep and from dogs and cats euthanized in animal shelters, etc. Most often refers to a fatty substance taken from the stomachs of pigs. Used in gum, food flavoring. Derivatives: stearamide, stearamine, stearates, stearic hydrazide, stearone, stearoxytrimethylsilane, stearoyl lactylic acid, stearyl betaine, stearyl imidazoline. Alternatives: Stearic acid can be found in many vegetable fats, coconut. Tallow, fatty alcohol: Rendered beef fat. May cause eczema and blackheads. Urea, uric acid, carbamide: Excreted from urine and other bodily fluids. Used to "brown" baked goods, such as pretzels. Derivatives: imidazolidinyl urea, uric acid. Vitamin A: Can come from fish liver oil (e.g., shark liver oil), egg yolk, butter, and synthetics. In vitamins, supplements. Alternatives: carrots, other vegetables, lemongrass, wheat germ oil. Vitamin B-12: Can come from animal products or bacteria cultures. Alternatives: Vegetarian vitamins, fortified soymilks, nutritional yeast, fortified faux meat substitutes. Vitamin B-12 is often listed as "cyanocobalamin" on food labels. Vegan health professionals caution that vegans get 5-10 mcg/day of vitamin B-12 from fortified foods or supplements . Vitamin D, ergocalciferol, vitamin D-2, ergosterol, provitamin D-2, calciferol, vitamin D-3: Vitamin D can come from fish liver oil, milk, egg yolk, etc. Vitamin D-2 can come from animal fats or plant sterols. Vitamin D-3 is always from an animal source. Alternatives: plant and mineral sources, completely vegetarian vitamins, exposure of skin to sunlight. Whey: A derivative of milk. Usually in cakes, cookies, candies, and breads. Used in cheese-making. Alternatives: soybean whey. Bear in mind, even though these are on our "bad" list, they are fine when derived from non-chemical, non-animal sources. # Scary-Sounding But Actually Harmless Ingredients a Alpha tocopherol, Alpha tocopherol acetate: Vitamin E derived from corn, peanuts, or soy. Arrowroot: A natural thickening starch, derived from the arrowroot plant. Absorbic acid: Synthetic vitamin C, often derived from corn. Brown rice syrup: A sweetener derived from brown rice. Cellulose: Plant fiber. Coconut Oil: Great for frying and baking because it can withstand high heats without becoming carcinogenic. Also helps the body metabolize fatty acids. Date Sugar: Sweetener derived from dates. Inulin: Present in many herbs. Acts as a probiotic and promotes healthy intestinal tract. Linoleic acid: Derived from corn, soy, or peanuts. Saffron: Natural food coloring derived from a plant. Sucanat: Sugar Cane Natural, a natural sweetener. Chapter 12 FYI U m, just because we wrote this book doesn't mean we're perfect. If you see us eating junk food or doing beer bongs, don't hold it against us. We believe in enjoying life _and_ maintaining a healthy balance. We're human. Also, we have some fat, gross body parts, too. We're women. Yeah, eating onions and garlic makes your breath smell like someone took a shit down your throat. But they fight cancer and help detoxify your liver. So eat 'em. What's all the drama surrounding hydrogenated oils? We'll tell you. Manufacturers add hydrogen to mono- or polyunsaturated fats (good fats), in order to change their consistencies. The end result, trans-fatty acids (bad), is a more solid product with a longer shelf life. Margarines, cookies, cakes, doughnuts, potato chips, meat and dairy products, and shortening can all contain hydrogenated oils. Trans-fatty acids can cause derangements of cell structure, accelerated aging, and a predisposition to diseases. Think about it. They are literally altering a naturally occurring product's molecular structure by adding hydrogen molecules to it. Eating these chemically altered foods containing hydrogenated oils will increase your risk of heart disease. Sad to say, heating oil at high temperatures also changes its natural molecular configuration and produces free-radicals. Free-radicals not only destroy essential fats and vitamins but are also linked to cancer and heart disease. This is why olive oil and peanut oil, which are both healthy, can be very _unhealthy_ in dishes like fried eggplant or French fries. Avoid eating fried foods (sniffle) and re-using heated oils. Never heat oil to the point where it is smoking. Cook with canola oil or coconut oil using low heat and for the shortest amount of time possible. Don't be a cheap asshole. Yeah, yeah, yeah, organic produce is usually more expensive than conventional produce. But we spend countless dollars on clothes, jewelry, manicures, magazines, rent or mortgages, car payments, and other bullshit. Surely our health and our bodies (we only get one body) are more important than anything else in our lives. Even if you are spending more on organic food, you'll save money in the long run if you're preparing more meals and snacks at home (which is always cheaper than buying food on the fly). Organic is worth the extra money, and you should aim to have everything you eat be organic. But especially when buying fruits or vegetables that you eat without peeling the skin. Always buy organic blueberries, strawberries, raspberries, apples, and pears. Peanuts and peanut butter, too, because conventional ones are loaded with pesticides. Buying organic produce is the only way to guarantee you're not eating genetically modified organisms. According to _Food Additives: A Shopper's Guide to What's Safe & What's Not,_ "genes are taken from one species of plant, animal or virus and inserted into another species in order to produce a desirable trait, such as disease resistance or hardier crops. No one knows the long-term effects of eating genetically modified foods. Genetically modified foods are being sold now and they are not being labeled. Certified organic foods are the only foods guaranteed not to be genetically modified." Brushing your teeth is a great way to ward off sweet cravings and stop yourself from eating. But, two or three times a day, every day for your entire life, you swallow trace amounts of toothpaste. What's in it? Chemicals? Artificial sweeteners? Would you eat it? Read the ingredients. Buy natural. The skin is the body's largest organ. Every day, we slop all sorts of potions and lotions and makeup on ourselves, and rub them into our skin. Ever read the ingredients of these products? Ever consider that you are putting chemicals directly onto your largest organ? Ever think about the pores all over your body and what you're putting inside them? Hopefully, you will now. Buy natural beauty products. What you put _on_ your body is just as important as what you put _in_ your body (because, in essence, what you put on your body will wind up in your body), especially on body parts you shave, pluck, or wax. Open pores do not want chemicals bulldozing through. Are your deodorant, makeup, perfumes, and lotions safe? You can get too much of a good thing. So don't overdose on water, or you'll flush necessary salt supplies right out of your body. Eight glasses a day is a good target. Natural, unrefined Celtic sea salt (different from table salt) contains many essential minerals, enhances organ function, and neutralizes toxins. It also contributes to the hydration of our cells and organs. Buy a food steamer. It will change your life. Do yoga. It is a kick-ass cardio workout that will strengthen, tone, and harden your muscles. Yoga is amazing for organ function, immune system strength, tackling insomnia, improving PMS symptoms and menstrual cramps, and overall health. You will love how it makes you look and feel. All kidding aside, if everyone did yoga, we would have world peace. Donate blood. You can save a life and lose weight at the same time. Keep your eyes peeled for bad press regarding veganism. It's usually planted by the industries that are threatened by the movement. Don't believe any of it. It's all bogus bullshit. One study claimed that feeding children a vegan diet was tantamount to child abuse. It just so happens that the National Cattlemen's Beef Association paid for the study. They had the gall to experiment on African children who were literally starving. These children were eating nothing but corn and beans in minuscule servings. When servings of meat were added to their diets, their health improved. Well, of course it did. They were fucking starving. This doesn't prove that veganism is dangerous or unhealthy. It just shows that the National Cattlemen's Beef Association will exploit starving, impoverished children to create bad press for veganism and boost its own meat sales. This is nothing short of a disgrace and an embarrassment to America. Chapter 13 Use Your Head D on't be a pig anymore. You know what you have to do, now do it. But don't go anorexic on us, either. It's easy to get caught up in any lifestyle change and go overboard. Make healthy choices and take excellent care of yourself without getting neurotic and obsessive. USE YOUR HEAD. We can't say it enough. Use your own head and think about what you are eating. Forget what you've ever read, heard, or learned and just think for yourself. Once they've recovered, your body, brain, and instincts will always lead you down the right food path. Obey them and disregard everyone and everything else. You know the truth. Read the ingredients. This goes hand in hand with using your head. If you plan on eating something, you should know exactly what it is. Even if it's a product that we've recommended, you still need to check the ingredients. Companies change their recipes all the time. Two vegan products we loved initially and suggested weren't vegan by the time we were finished writing this book, and we had to remove them from our recommendation lists. Trust no one. Not even us. Some of the products on our suggested food lists aren't perfect; we make certain allowances based on our own opinions and desires. Read and decide for yourself. And if you don't recognize an ingredient, call the company's 800 number on the package and ask what it is. If it's not something you would put in your body, tell them, and suggest that they improve their product. Companies really do take comments into account, so always voice your opinion. Now that you're a Skinny Bitch, don't turn into a skinny bitch. We conceived of the title, _Skinny Bitch_ , to get attention and sell books. We just wanted to spread our message far and wide and thought _Skinny Bitch_ was a good way to do it. But we are not bitches, and we have no desire to promote bitchiness. There is nothing uglier than a pretty woman who's nasty. If you look great, you should feel good about yourself and be happy. Instead of fixating on the last five pounds you want to lose, celebrate the five you already lost. Progress, not perfection. Don't be insecure or competitive or feel threatened by women who are thinner or prettier than you. Be happy for them; it will make you look better. Smile a lot, give compliments out whenever you can, and be nice to everyone. You'll just keep getting prettier and prettier and skinnier and skinnier. Soon, you'll notice people (especially men) flocking to the new you. Not just because you're skinny but because you are happier, healthier, and eating a cruelty-free diet. So feel free to share your new wealth of information with everyone who asks. Spread the good word, but be careful not to preach. You'll see that some people get very defensive about their diets when you tell them about yours. Even if you are being very non-judgmental, people may feel threatened by your righteousness. Understandably, your being a vegan shines a spotlight on the cruelty they're contributing to, and it makes them feel uncomfortable. When asked, you can describe what you've learned about the treatment of farm animals and all of the health benefits of being vegan. By all means, let people know how great you feel and how much weight you've lost. But never suggest that they try it or make them feel bad about their diet. Offer to lend them your copy of _Skinny Bitch_ , or give them the GoVeg.com website. But don't push it. Everyone seeks the truth in his or her own time. Now that you've got your diet, health, and appearances under control, fix other areas of your life. After all, there's no point in being gorgeous if your life is a mess. End your co-dependent relationship, quit your dead-end job, and ditch your toxic friends. Make a list of goals and start chipping away at them. THIS IS YOUR LIFE! Live it to the fullest with reckless abandon. Seize the day. And do it again tomorrow. Live. Go get your dream job. Search for your dream man. Fear nothing. Try everything. Be excited. Dance. You'll never get yesterday back, but today is yours for the taking. Make it great. Bravo. You've got your life and your diet on-track. But you still need to move your ass. Exercise will boost your self-esteem, reduce your junk-food cravings, and help you _lose weight_. If you can commit to a gym routine, fantastic! You will reach your fitness goals faster. But you don't need to be a gym rat. Just do something! It can even be fun. Take a class that you've always wondered about, like kickboxing or belly dancing. Go for walks after dinner or bike rides on weekends. Better yet, walk or bike to work. Whatever you choose, exercise makes you feel great about yourself. And that alone is priceless. You _are_ what you _think_. Our thoughts, feelings, beliefs, and experiences create tangible, concrete reactions at cellular and atomic levels. So whether something is "real" or not doesn't matter. If we think, feel, believe, or experience it, it will become a reality. Slow down and think about this and realize the implications it can have on your life. It can work for or against you. For example, if you _think_ you are fat and that diets never work and that you'll always be fat, then yes, you _are_ fat and diets never work and you will always be fat. What you _think_ actually becomes embedded in your brain and your cells and the energy field surrounding you. Your thoughts are just that powerful. So if you _feel_ you are meant to be thin, and _believe Skinny Bitch_ will make you lose weight and _know_ that this book is going to change your life, you _will_ be thin, you _will_ lose weight, and your life _will_ change. It is just that simple. In her book, _Anatomy of the Spirit_ , Dr. Caroline Myss examines the unquestionable link between negative emotions and physical illnesses. Take "Julie," for example. Julie's husband treated her with contempt and disdain, frequently said the mere sight of her repulsed him, and refused to sleep with her. It is no coincidence that Julie was diagnosed with breast and ovarian cancer, reflecting her lack of self-love for her "womanhood." She could not leave her husband. She never recovered from her cancer and died as a result. "Joanna" was married to a man who had multiple affairs, which she knew about but tried to live with. Not surprisingly, she developed breast cancer. Eventually, she confronted her husband and demanded fidelity. However, he was unable to change, so she left the marriage. Joanna recovered from her cancer. _Anatomy of the Spirit_ chronicles one history after another of people sickening themselves or healing themselves with thought and emotion. (Of course, we are not suggesting that everyone suffering from a disease has brought it upon him or herself. We are, however, saying it is entirely possible to do so.) Our minds are infinitely powerful. Our favorite self-help gurus, Dr. Wayne Dyer, Louise Hay, and Tony Robbins, understand this, and they all preach the power of daily affirmations. An affirmation is a positive statement you make that allows you to clearly envision a goal or mindset. It is declared as if it is already happening, and it can be anything you want: "Every day in every way my ass is getting smaller." "Every day in every way my thighs are getting thinner." "Every day in every way my stomach is getting flatter." "Every day in every way I'm losing more and more weight." "Every day in every way I'm loving my body more." "Every day in every way I'm getting healthier and healthier." Create your own affirmations and say them (in your head or aloud, if you can) when you wake up in the morning, while exercising, in your car, and in bed at night. You will immediately notice how good they make you feel and you will be astonished at the results. This book is the result of our affirmations, so we _know_ they truly work. Now that you love yourself, wear sexy clothes. You worked hard for this body and you should be proud of it. We know it can be terrifying to wear something super-trendy—like you don't have the right or aren't worthy. But you _are_ good enough, you _do_ deserve it, and no one is thinking otherwise. So don't be afraid of wearing revealing, high-fashion clothes. This is your body for this lifetime. Dress it up and love it. Why are you "saving" all your good underwear or hot outfits? Wear them, fool. But please keep in mind that looking cheap or cheesy doesn't accomplish anything. If you have poor fashion sense (you know who you are), ask someone for guidance. Now we know we keep encouraging you to look your best, but, for the love of God, don't associate your worth with your appearance. We are spiritual beings walking around in these crazy skin suits. Our insides are much more important than our outsides. So don't you fucking dare measure your worth by the amount of attention or validation you get from men. It's nice to be appreciated, but it is not a necessity. Love yourself and your looks, even if no one else seems to. In time, your confidence and self-love will attract a winner. Well, it's all there in black and white. We sincerely hope you will take the knowledge you've learned and put it to use from this moment on. YOU hold the power to change your life, and it's really so simple. Use your head, lose your ass. Afterword I sn't man an amazing animal? He kills wildlife by the millions in order to protect his domestic animals and their feed. Then he kills domestic animals by the billions and eats them. This in turn kills man by the millions, because eating all those animals leads to degenerative—and fatal—health conditions like heart disease, kidney disease, and cancer. So then man tortures and kills millions more animals to look for cures for these diseases. Elsewhere, millions of other human beings are being killed by hunger and malnutrition because food they could eat is being used to fatten domestic animals. Meanwhile, some people are dying of sad laughter at the absurdity of man, who kills so easily and so violently, and once a year sends out cards praying for "Peace on Earth." —Preface from _Old MacDonald's Factory Farm,_ by C. David Coates Recommended Reading # Books** _Slaughterhouse,_ Gail A. Eisnitz. This book is an absolute must-read for every American who has ever eaten meat, is still considering eating meat, or isn't sure if they should or shouldn't. Buy this book today! _Breaking the Food Seduction,_ Neal Barnard, M.D. _Carbophobia: The Sorry Truth About America's Low-Carb Craze,_ Michael Greger, M.D. _The China Study,_ T. Colin Campbell, Ph.D. and Tomas M. Campbell, II _Diet For a Poisoned Planet,_ David Steinman _Dominion,_ Matthew Scully _Eat More, Weigh Less,_ Dean Ornish, M.D. _Fast Food Nation,_ Eric Schlosser _The Food Revolution,_ John Robbins _The McDougall Program,_ John McDougall, M.D. and Mary McDougall _Prevent and Reverse Heart Disease,_ Caldwell B. Esselstyn, Jr., M.D. _The Way We Eat,_ Jim Mason and Peter Singer # Spiritual/Self-Help Books/CDs* _Your Erroneous Zones,_ Dr. Wayne Dyer _Real Magic,_ Dr. Wayne Dyer _You'll See It When You Believe It,_ Dr. Wayne Dyer _Notes from a Friend,_ Anthony Robbins _Get the Edge CDs,_ Anthony Robbins _You Can Heal Your Life,_ Louise L. Hay _Anatomy of the Spirit,_ Caroline Myss, Ph.D. # Cookbooks _Skinny Bitch in the Kitch,_ yours truly, Rory Freedman and Kim Barnouin _The Uncheese Cookbook,_ Joanne Stepaniak _The Garden of Vegan,_ Tanya Barnard and Sara Kramer _How it All Vegan,_ by Tanya Barnard and Sara Kramer _The Compassionate Cook,_ PETA and Ingrid Newkirk _CalciYum,_ David and Rachelle Bronfman _The Native Foods Restaurant Cookbook,_ Tanya Petrovna _The Candle Café Cookbook,_ Joy Pierson and Bart Potenza with Barbara Scott-Goodman _Vegan Planet,_ Robin Robertson _Veganomicon,_ Isa Chandra Moskowitz and Terry Hope Romero _Viva le Vegan!,_ Dreena Burton _Very Vegetarian,_ Jannequin Bennet _The Vegan Table,_ Colleen Patrick Goudreau _The Joy of Vegan Baking,_ Colleen Patrick Goudreau Veganpeace.com offers recipes and reviews of veggie cookbooks # Restaurant Guides happycow.net (This site is heaven on Earth! You can find all the veggie-friendly restaurants in your 'hood, and, when you travel, you can make sure you know all the local haunts.) vegoutguide.com # Merchandise Web Sites veganstore.com VeganEssentials.com AnimalRightsStuff.com AlternativeOutfitters.com feelgoodtees.com mooshoes.com veganunlimited.com TheVegetarianSite.com VegSexShop.com # Web Sites skinnybitch.net GoVeg.com meat.org peta.org farmsanctuary.org pcrm.org cok.net protectinganimals.org veganmd.org atkinsexposed.org VeganOutreach.org afa-online.org informedeating.org organicconsumers.org holisticmed.com congress.org anthonyrobbinsdc.com drwaynedyer.com hayhouse.com oa.org (overeaters anonymous), 505-891-2664 # Food Web Sites vegieworld.com deliciouschoices.com veganstore.com rawbalance.com playfood.org TreeHugginTreats.com simpletreats.com chocolatedecadence.com leaheyfoods.com vegandreams.com goodbaker.com rosecitychocolates.com eatraw.com nutrilicious.com allisonsgourmet.com healthy-eating.com Sources Consulted Armstrong, Clare, MS, RD. 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Whitney and Rolfes, _Understanding Nutrition_ , 44 Diamond, _Fit for Life_ , 65-69. Chandel, "Sweet Poison," The Sunday Tribune Spectrum, tribuneindia.com. "Sugar Blues," Natural Nutrition, livrite.com. Chandel. "Soft Drinks, High-Fructose Corn Syrup Promote Diabetes, Says Study," newstarget.com. Davis, "A Tale of Two Sweeteners: Aspartame & Stevia," suewidemark. netfirms.com. "Natural Sweeteners, Natural Nutrition, livrite.com. Gold, "Common Toxic and Substances to Avoid," holisticmed. com. Murray, "How Aspartame Became Legal—The Timeline," quantumbalancing.com. Ibid. Ibid. "Department of Health and Human Services-Symptoms Attributed to Aspartame in Complaints Submitted to the FDA," U.S. Department of Health and Human Services, presidiotex.com. Johnson," Aspartame . . . A Killer!" _The Sunday Express London,_ newfrontier.com. Hasselberger, "Aspartame: RICO Complaint filed Against Nutra-Sweet, ADA, Monsanto," newmediaexplorer.org. Young, 89. Gold, "The Bitter Truth about Artificial Sweeteners," truthcampaign.ukf.net. _Webster's New World Dictionary_ (1982), s.v. "saccharin." Mercola, "The Potential Dangers of Sucralose, vitaminlady.com Mercola, "Splenda—Here We Go Again," mercola.com. Mercola, "The Potential Dangers of Sucralose." Burros, "Splenda's 'Sugar' Claim Unites Odd Couple of Nutrition Wars," _New York Times,_ skyhen.org. Young, 50-51. Ibid., 14-15. "10 Reasons To Avoid Acidosis." Young, 51-52. Weil, _Natural Health, Natural Medicine,_ 27. Fuhrman, _Eat to Live,_ 98. Ibid., 95. Robbins, _Diet for a New America,_ 290. Grace, _A Way Out,_ 8-9. Ibid., 8-10. Steinman, 76. Brownlee, "The Beef about UTIs." Steinman, 73. Cousens, _Conscious Eating,_ 433. Ibid., 315. Ibid., 322. Ibid., 313. Wijers-Hasegawa, "Bayer's GE Crop Herbicide, Glufosinate, Causes Brain Damage." Cousens, 438. Steinman, 90. Ibid., 80. "Men's Health Warns of Foods You Should Never Eat," Peta.org. Baillie-Hamilton, _The Body Restoration Plan,_ 36. Ibid., 34-5. "FDA Approved Animal Drug Products," FDA 'Green Book' section. Mason and Singer, _Animal Factories,_ 75. "The Latest In Cancer: 'White Meat' Linked to Colon Cancer," pcrm.org; Singh PN, Fraser GE. Dietary risk factors for colon cancer in a low-risk population. Am J Epidem 1998; 148:761-74. Ibid. Robbins, 303. Steinman, 73. Ibid., 313-14. "Fish and Shellfish: Contamination Problems Preclude Inclusion in the Dietary Guidelines for Americans," pcrm.org, Spring 2004. Weiss, _Reader's Digest: Foods that Harm, Foods that Heal,_ 345. Weil, _Natural Health, Natural Medicine,_ 37. Weil, "Does Soy Have a Dark Side?" drandrewweilselfhealing.com. Diamond, _Fit For Life II,_ 242. Cousens, 479. "10 Reasons To Avoid Acidosis," PolyMVASurvisors.com. Diamond, _Fit For Life II,_ 243. "Milk Sucks," milksucks.com. Ibid. Ibid. Cohen, "The Essence of Betrayal," notmilk.com. Wangen "Food Allergy Solutions Review," FoodAllergySolutions.com. "Milk Sucks: Find Out more," milksucks.com. "Two New Studies Sour Milk's Image," pcrm.org. Robbins, 150. Steinman, 131-132. "Milk Sucks," milksucks.com. Cousens, 478. Steinman, 122. Holford, _The Optimum Nutrition Bible_ , 42. Robbins, 164. Cousens, 316. Weiss, 87. Eisnitz, _Slaughterhouse,_ 20, 24-25, 31. Ibid, 66. Ibid., 69-70. Ibid., 126-133. Ibid., 29. Ibid., 20, 28-29. Ibid., 71. Ibid., 166. Ibid. Ibid. Ibid. Ibid., front jacket. Ibid., 124. Ibid., 82. Ibid., 125. Ibid., 87. Ibid., 84. Ibid., 91. Ibid., 93. Ibid., 130. Ibid., 132. Ibid., 132-133. Ibid., 144-145. Ibid., 145. Ibid., 93. Ibid., 133. Ibid., 140-141. Ibid., 172. Ibid. Ibid., 173. Ibid., 174. Ibid., 175. Leake, "The rich emotional & intellectual lives of cows." "The Hidden Lives of Chickens," Peta.org. "Pigs: Smart Animals at the Mercy of the Pork Industry," Peta.org. "Fish Feel Pain," Fishinghurts.com. "Free-Range Eggs and Meat: Conning Consumers?" Peta.org. "Investigation Reveals Slaughter Horrors at Agriprocessors," Peta.org. Eisnitz, "Ask the Experts," Peta.org. Eisnitz, _Slaughterhouse,_ 125. Brown, e-mail. "Animal Friendly Quotes," Peta.org. "Everything you need to eat right for your health," Peta.org. "Factory Farming: Environmental Consequences," Animalalliance.ca. Cook, "Environmental Hogwash," inthesetimes.com. Cousens, 442. Young, 82-3. Howell, _Enzyme Nutrition,_ 4. Ibid., 4-5. Cousens, 299. Ibid., 299. Ibid., 313. Ibid., 417. Holford, 29. Cousens, 312. Ibid. Holford, 41. Cousens, 587. "Vegetarian and Vegan Famous Athletes," Veggie.org. Weil, _Natural Health, Natural Medicine,_ 30. Young, 68. Whitney and Rolfes, _Understanding Nutrition,_ 8th ed., 130-31. Kamen, _New Facts About Fiber,_ 43-85. Ibid., 14. Ibid., 10. Holford, 109. "About USDA," U.S. Department of Agriculture. Schlosser, "The Cow Jumped Over the U.S.D.A," _New York Times,_ common-dreams.org. Simon, "The Politics of Meat and Dairy," earthsave.org. Langeland, "Tainted Meat, Tainted Money: Consumer groups decry coziness between government, agribusiness," _Colorado Springs Independent online._ Schlosser, "The Cow Jumped Over the U.S.D.A." Ibid. Ibid. "National Animal Identification System: Goal and Vision," U.S. Department of Agriculture APIS Veterinary Services. Ibid. "USDA Cover-Up of Mad Cow Cases," organic-consumers.org "USDA won't stop use of illegal hormones in the veal industry: cancer rates skyrocket in humans," newstarget.com. Nestle, _Food Politics: How the Food Industry Influences Nutrition and Health,_ 73. Ibid. "Common Dairy Digestive Under-Recognized and Under-Diagnosed in Minorities," Johnson & Johnson. Simon, "Dairy Industry Propaganda: Tale of Two Mega-Campaigns," originally published on vegan.com. "Surgeon General Asks: Got Bones?" gotmilk.com. Simon, "Dairy Industry Propaganda." "Surgeon General Asks: Got Bones?" "About USDA." Simon, "The Politics of Meat and Dairy." Simon, "Misery on the Menu: The National School Lunch Program," originally published in _The Animal's Agenda,_ informedeating.org. Schlosser, _Fast Food Nation,_ 219-20. Simon, "Misery on the Menu." "Food and Nutrition Assistance Programs," Economic Research Service, USDA.gov. Simon, "The Politics of Meat and Dairy." Ness, "Organic Food: Outcry Over Rule Changes that Allow More Pesticides, Hormones," _The San Francisco Chronicle,_ commondreams.org. "Organic Industry and Consumers Celebrate USDA Reversal on Non-Food National Organic Standards," The Weston A. Price Foundation, westonaprice.org. Harris, "Organic Consumers Association (OCA), the Nation's Largest Organic Consumer Group Denounces Degradation of Organic Food Standards by Congress," about.com. "Organic Industry and Consumers Celebrate USDA Reversal on Non-Food National Organic Standards." Krebs, "USDA Accused of Allowing 'Sham' Certifiers to Participate in National organic Program," _The Agribusiness Examiner._ "OCA and Environmental Groups Sue USDA to Enforce Strict Standards: Environmental Groups Back Harvey Lawsuit," Organic Business News, organicconsumers.org. "Nation's Largest Organic Dairy Brand, Horizon, Accused of Violating Organic Standards," The Cornucopia Institute. Simon, "The Politics of Meat and Dairy." Green, "Not Milk: The USDA, Monsanto, and the U.S. Dairy Industry," _LiP Magazine._ Ibid. "The U.S. Food and Drug Administration (FDA) and the glutamate industry," truthinlabeling.org. "Food Additives," new-fitness. com. "Banned as Human Food, StarLink Corn Found in Food Aid," _Environmental News Service._ Greger, "Rocket Fuel in Milk," Dr.Greger.org. Ibid. Cook. Ibid. Schlosser, _Fast Food Nation,_ 210-214. Cook. Barnard, _Breaking the Food Seduction,_ 17-19. Ibid., 20-21. Ibid., 50-51. Ibid., 52. Ibid., 53. Diamond, _Fit For Life II,_ 245. Barnard, 99-102. Ibid., 111-14. Cousens, 231-32. Van Straten, _Super Detox,_ 12. Cousens, 231-34. Ibid., 232. Van Staten, 13. Cousens, 233. Ibid., 234. Ibid., 231. Mindell, _Earl Mindell's New_ _Vitamin Bible,_ 39-127. Boschen, "Cycles of the Body," thejuiceguy.com. Farlow, _Food Additives: A Shopper's Guide To What's Safe & What's Not,_ 7-75; "Caring Consumer Guide," Peta.org. Weil, _Natural Health, Natural Medicine,_ 17-18. Holford, 24. Farlow, 41-2. "Salts that Heal and Salts that Kill," curezone.com. "National Cattlemen's Beef Association Pays for Sadistic Anti-Vegan 'Study,' " vegsource.com. Myss, _Anatomy of the Spirit,_ 53-55. P.S. Wait! We have a confession to make. We really couldn't care less about being skinny. Don't get scared or upset; you will definitely lose weight if you adopt the _Skinny Bitch_ lifestyle. However, our real hope is for you to become healthy. We don't want anyone to be obsessed with getting skinny. When you eat right and exercise, you feel strong and healthy and confident. You start loving your body—not because you lose weight—but because you feel great. It's an inside job. You're finally treating your body like the temple it is. Comparison is the thief of joy. No matter what we do, most of us will never look like supermodels or celebrities. And accepting that will make our lives a whole lot better. So what if there is only one standard of beauty perpetuated by Hollywood that you don't fit into? Don't buy into that bullshit. Take excellent care of the body you were blessed with, and love, love, love it! —Rory Freedman and Kim Barnouin a Sourced from _Food Additives: A Shopper's Guide To What's Safe & What's No_t by Christine Hoza Farlow, D.C., and PETA's _Caring Consumer Guide._ 220 © 2005 by Rory Freedman and Kim Barnouin All rights reserved under the Pan-American and International Copyright Conventions _This book may not be reproduced in whole or in part, in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system now known or hereafter invented, without written permission from the publisher._ Library of Congress Control Number 2005901966 eISBN : 978-0-762-43275-2 Typography: Bauer Bodoni and Dutch 801 Running Press Book Publishers 2300 Chestnut Street Philadelphia, Pennsylvania 19103 Visit us on the web! www.runningpress.com www.skinnybitch.net
--- author: - 'Jr-Wei Tsai, John H. Simonetti, Bernadine Akukwe, Brandon Bear, Jonathan D. Gough, Peter Shawhan, Michael Kavic' title: Simultaneous Observations of Giant Pulses from Pulsar PSR B0950+08 at 42 MHz and 74 MHz --- Introduction ============ One year after the discovery of the first pulsar in 1967 [@1968Natur.217..709H], the first giant pulse (GP) was detected from the Crab pulsar (PSR B0531+21) by @1968Sci...162.1481S. GPs have an observed flux density that is tens or hundreds of times larger than for an average pulse (AP). Observations of GPs can illuminate the underlying pulsar pulse production mechanism and can serve as an effective probe of the interstellar medium (ISM). Moreover, simultaneous observations at multiple frequencies allow for a more nuanced investigation of these phenomena. In the current work we perform such an analysis using simultaneous observation of PSR B0950+08 at 42 and 74 MHz. These observations were conducted using the first station of the Long Wavelength Array (LWA1) [@2013ITAP...61.2540E]. Only a small minority of pulsars emit GPs. Initially, all pulsars observed to emit GPs were found to possess a very strong magnetic field in the region of the pulsar’s light cone, with $B_{LC}>10^5$ G [@1996ApJ...457L..81C]. This changed with the observations of PSR B0950+08 by , indicating that pulsars with a lower $B_{LC}$ (150 G for PSR B0950+08) can also emit giant pulses. Another common property of GPs is that they exhibit a non-Gaussian power-law distribution in the peak flux density. GP observations of PSR B0950+08 over the frequency range 39-111 MHz indicate further that the rate and strength of GP emission is reduced at $\sim$39 MHz as compared to $\sim$100 MHz [@2012AJ....144..155S; @2012ARep...56..430S; @2015AJ....149...65T]. In this paper we extend the previous study of PSR B0950+08 by @2015AJ....149...65T with simultaneous observations at two frequencies of 42 and 74 MHz. We detected 275 and 465 GPs at 42 and 74 MHz, respectively. The rate and strength of these GPs are less than has been observed at $\sim$100 MHz. This indicates that this pulsar is weaker and produces less frequent GPs below 100 MHz, than above 100 MHz. We found the AP has a width which is consistent with previous observations. We detected no other transient pulses with signal-to-noise ratio (SNR) $>7$ over a wide range of dispersion measures range from 1 to 5000 pc cm$^{-3}$. Simultaneous observations of pulses at multiple frequencies can be used to investigate the pulsar’s beam structure. In particular it is possible to analyze the emission altitude difference for the simultaneous observations. We can infer emission altitude from the peak-to-peak separation of double-peaked pulses at different frequencies, assuming a dipolar magnetic field of the pulsar. We determined the emission altitude in the context of a dipolar magnetic field for our set of observations for both GPs and APs. We found $r$(42 MHz) = 29.27 km ($0.242\%$ of $R_{LC}$) and $r$(74 MHz) = 29.01 km ($0.240\%$ of $R_{LC}$) for the average pulse, while for giant pulses, $r$(42 MHz) = 29.10 km ($0.241\%$ of $R_{LC}$) and $r$(74 MHz) = 28.95 km ($0.240\%$ of $R_{LC}$). The $R_{LC}$ is the light cylinder radius of this pulsar. The mean peak-to-peak separation of GPs is smaller than APs for both observing frequencies. Observations of pulsars have been used to probe the spatial spectrum of irregularities in the ISM. Temporal pulse widths, at different frequencies, can be used to determine the spectral index of a power law describing the interstellar irregularities. The most commonly discussed power law is for a Kolmogorov spectrum. Our previous observations of PSR B0950+08 suggested that the spectrum along this line-of-sight deviates from Kolmogorov [@2015AJ....149...65T]. In this work, we explore this issue further by considering the effect of scattering on the GPs and APs simultaneous observed at two frequencies. To analyze the scattering effect we made use of the CLEAN-based algorithm [@2003ApJ...584..782B] to determine the exponential decay time for APs and pulses with SNR $>7$, assuming a thin screen scattering model. We found different exponential decay time from pulses with SNR$>7$ (2.5$\pm1.3$/1.1$\pm0.7$ ms for 42/74 MHz) and AP (5.4/3.4 ms for 42/74 MHz). Because the scattering effect from the ISM should be the same for individual pulses or average profiles, there should be other effects that dominate the pulse broadening, so we still can not determine the scattering time of PSR B0950+08 for frequency down to 42 MHz. We detail our observations and data reduction in section \[obanddr\]. Next we explain the scattering model used as well as the method for determining flux densities. We describe the pulse behavior from observation in section \[behaviorofpsr\]. We then discuss the interpretation of these results in the context the cone structure beam model in section \[sect:altitudes\] and scattering in section \[sect:scattering\]. Finally we summarize our main findings in section \[sect:conclusion\]. Observations and Data Reduction {#obanddr} =============================== LWA1 [@2011ITAP...59.1855E] is a radio telescope array operating in the frequency range 10–88 MHz, located in central New Mexico. The telescope consists of 256 dual-polarized dipole antennas distributed over an area of about 110 m by 100 m, plus 5 outliers at distances of 200–500 m from the core of the array, for a total of 261 dual-polarized antennas. The outputs of the dipoles are individually digitized and can be formed into beams (DRX beam-forming mode). Four fully independent dual-polarization beams capable of pointing anywhere in the sky are available; each beam has two independent frequency tunings (selectable from the range 10–88 MHz) with bandwidths of up to about 17 MHz. The full-width at half-maximum (FWHM) beamwidth for zenith pointing is approximately $4.3^\circ$ at 74 MHz and depends on observing frequency as $\nu^{-1.5}$. The system temperature is dominated by the Galactic emission and so the beam sensitivity of the instrument is dependent on the LST of the observation and the direction of the beam. The ability of the LWA1 to observe two frequencies simultaneously provides a powerful tool for studying radio sources. The simultaneity of observations at different frequencies is useful for studying the profile frequency dependence and the temporal broadening of pulses @2013ITAP...61.2540E. Observations of PSR B0950+08 were conducted using LWA1 in beam forming mode from January 25 through January 27, 2014. The observation set is composed of 4 consecutive hours of data from each day beginning 2 hours before the pulsar passed the meridian. Observations were made at two frequencies simultaneously, centered at 42 and 74 MHz, each with a bandwidth of 16 MHz (due to low sensitivity). Two polarizations were recorded. Using routines from the LWA Software Library (LSL) [@Dowell:2012rt], we performed a 4096-channel Fast Fourier Transform (FFT) on each 0.209 ms of raw data, dividing the 19.6 MHz observing bandwidth into channels of 4.785 kHz. Radio frequency interference (RFI) mitigation was performed on the data set, using the following procedure. First, we obtained the average spectrum for each 2.09 second interval (each set of 10,000 consecutive spectra). Next, we fit a 16th order polynomial to the 2.09 second average spectrum, and divided that average spectrum by the polynomial. The 16th order polynomial is the lowest order that fit the approximately 16 ripples in the bandpass, without undue suppression of narrow-band RFI. Finally, any frequency bin in the 2.09 second average spectrum that was greater than 3$\sigma$ above the mean was masked as RFI in all the corresponding 0.209 ms spectra. The shape of the observed bandpass is not constant in time, and this variation must be removed to allow for an effective search for transient pulses. The variation in the spectrum is dominated by the diurnal variation of the Galactic background. Once the RFI-contaminated frequency bins were identified and masked, we determined and removed the varying shape of the bandpass using the following procedure. First, for each 2.09 s of data, we computed a median spectrum for the 10,000 RFI-masked spectra. Then, we used 150 such spectra to compute the median spectrum for approximately 5 minutes of observations. The 5 minute duration was chosen so the diurnal variation of the Galactic background was effectively smoothed out. To further smooth the 5 minute spectrum, we performed a moving boxcar average across the 5 minute median-spectrum; the boxcar length used was 101 frequency channels. Finally, we divided each 0.209 ms spectrum by the boxcar-smoothed spectrum corresponding to its epoch. To prepare for further analysis we removed the first 360 channels and the last 395 channels from each spectrum, removing any end effects, and leaving a final bandwidth of 16 MHz. The final spectra were arranged into spectrograms of frequency (vertical axis) and time (horizontal axis). @2003ApJ...596.1142C describe in detail a technique suitable for searching for individual pulses of various origins, including pulsar GPs, in time-frequency data such as ours. As a first look, we used this method on our data, taken in chunks of 5 minute duration. In essence, the technique consists of constructing dedispersed time series for a range of candidate DMs and smoothing each individual time series with effectively larger and larger averaging-boxcars to search for pulses of temporal width matched to the smoothing time — which yields the best SNR for a candidate pulse. Pulses of strengths and numbers larger than expected for the (assumed) Gaussian noise in our data are pulses of possible astrophysical origin. (Another possibility is that they are RFI or other transient non-astrophysical events, but candidate pulses of the correct DM for PSR B0950+08 are more likely to be our sought-after pulsar pulses.) We performed incoherent dedispersion (summing intensities) in our spectrograms. We searched through time series for 28,451 candidate DMs in this manner, ranging from 1 to 5000 pc cm$^{-3}$ with a DM spacing $\delta$DM $= 0.0003$ DM. The time series was smoothed in steps by averaging a moving boxcar of width equal to 2 time samples, and then removing one of the resulting time samples. Repeated smoothing and decimating in this manner efficiently produces a set of time series of increasing smoothness. At each smoothing and decimation step the resulting time series are searched for pulses. We performed 15 such steps for each dedispersed time series. Thus, the final time sample duration in the last-smoothed time series was $2^{15}\times0.2089~{\rm ms} = 6.85$ s. In the entire search we found all transient events in the resulting time series with SNRs $\gtrsim$ 6.5 were for a DM of 2.97 pc cm$^{-3}$, the DM for PSR B0950+08. No such strong pulses were found at other DMs. Furthermore, the expected number of transient events due to Gaussian noise matches well our numbers of events at SNR$<$6.5, but events of SNR$>$6.5 are more numerous than expected from Gaussian noise alone, and appear at the DM of the pulsar. Thus we are confident that by focusing on transient events that have a SNR$>$6.5, determined through this procedure, we are selecting pulses produced by PSR B0950+08. We note here that the SNR determined for a pulse by the Cordes-McLaughlin procedure is computed in the time series smoothed to the temporal width of the pulse. This is a precise means of quantifying the SNR of a temporally-isolated single, dispersed pulse, and, as such, is perhaps reasonable for describing anomalously intense pulses or GPs, which tend to be isolated. But, it should be noted that quoted pulsar flux densities are averages in time, including both energy received during pulses, and between pulses, i.e., effectively zero. Thus, when we measure the flux density of our GPs and compare them to APs, we will adopt the more conventional time-average throughout a pulse period. Behavior of Pulses {#behaviorofpsr} ================== To study the flux density and phase of pulses we fit multiple Gaussians to both APs and GPs as both exhibited multiple-peak profiles. The multiple Gaussian fits at both frequencies enable a simple comparison of the pulses at both frequencies. Because the two observing frequencies are recorded simultaneously the relative phase can be determined after dedispersion. We dedispersed the two frequencies independently using the same DM but produced separate dedispersed time series. The flux density and phase of peaks were determined from the fitted Gaussians. The flux density is calculated by converting the area under the fitted curves to the system equivalent flux density (SEFD). The flux density ratio of a GP and the AP is the ratio of the area under the fitted curves, while the area of the AP was divided by the number of pulses folded. Flux density ------------ Our observations did not include any drift scans on other objects for calibration, so we obtain rough flux densities for the AP and GPs using an estimated SEFD. The SEFD is the flux density a source in the beam needs to produce a SNR of unity, for an observation of 1 Hz bandwidth and integration time of 1 second. At low frequencies, the Galactic noise is the dominant contribution to system noise. Ellingson established a rough model for estimating the SEFD, which takes account of the combined effects of all sources of noise [@Ellingsonsen]. Ellingson uses a spatially uniform sky brightness temperature $T_B$ in his model, dependent on observing frequency $\nu$, where $$T_b = 9751 \mbox{K} \left(\frac{\nu}{38\mbox{MHz}}\right)^{-2.55} \label{eqn:brightness temperature}$$ and ignores the ground temperature contribution as negligible. The receiver noise is about 250 K, but has little influence on the SEFD. This model when applied to LWA1 shows that the correlation of the Galactic noise between antennas significantly desensitizes the array for beam pointings that are not close to the zenith. It is also shown that considerable improvement is possible using beam-forming coefficients that are designed to optimize SNR under these conditions. @2013ITAP...61.2540E checked this model with observations of strong flux density calibrators, finding the results roughly correct. Based on the model of Ellingson and his drift scan results, and given our observations at transit are for non-zero zenith angle, we can estimate an appropriate SEFD to use for our observations, with an uncertainty of roughly 50%. The SNR of pulses away from the moment of transit are corrected by a factor which compensates for decreasing effective collecting area and increasing SEFD, with increasing zenith angle. Thus, the flux density we assign to a pulse, as averaged across the entire pulse period, is $$S = \frac{\rm SEFD}{\sqrt{2B\Delta t}}\ \frac{1}{N_{\rm bins}} \sum_{i=1}^{N_{\rm bins}} \frac{I_i}{\rm rms} = \frac{\rm SEFD}{\sqrt{2B\Delta t}}\ {\rm \overline{SNR}} \label{eqn:flux density}$$ where $B$ in Hz is the bandwidth, $\Delta t$ in seconds is the duration of a time sample, $N_{\rm bins}$ is the number of time samples (bins) in a pulse period, the sum is over the full pulse period, the $I_i$ are the intensity values (arbitrary units) in the Gaussian pulse profile fitted to a pulse (a baseline average was already subtracted from the data), rms is measured in the baseline, and the $\rm \overline{SNR}$ is the average SNR during the pulse period. Using @2013ITAP...61.2540E we assume the same SEFD of 15,000 Jy ($\pm$50%) for both observing frequencies while transiting at a zenith angle of about 26$^\circ$. The sensitivity of LWA1 is also dependent on the altitude of the target. To correct for this effect we calculated sequences of 24 minute averages of the pulse flux densities and fit the variation with a polynomial function, with a maximum value of unity at or near the meridian, as shown in Figure \[altitudecorr\]. Then the flux of any particular pulse was divided by the polynomial to remove the zenith angle dependence for future analysis. Profile of PSR B0950+08 {#profile0950} ----------------------- An adequate fit to the pulse profiles required three Gaussian components, as demonstrated in Figure \[phasesingledouble0950\]. While comparing the AP profile at two frequencies, we noted that the leading peak position does not shift more than a temporal bin, while the second peak’s shift is more obvious. The width of the AP measured at the half maximum height from the leading to trailing components, $W$, is 25.6 ms and 17.8 ms at 42 and 74 MHz respectively. Figure \[pulsewidthindex\] shows $W$ for frequencies above 20 MHz. We find a temporal broadening spectral index of $\xi = -0. 49\pm0.064$ when our observations are fit along with other observations of this pulsar at frequencies from 20 to 410 MHz, as shown in Figure \[pulsewidthindex\]. The spectral index seems to change at about 0.5 GHz. The period-averaged flux densities are 2.8 Jy and 2.4 Jy at 42 and 74 MHz, respectively. Figure \[fluxspectra0950\] shows flux densities for APs at frequencies of 20 MHz and above, along with observations of GPs by @2012AJ....144..155S at 103 MHz and @2012ARep...56..430S at 112 MHz. In addition, we have added data points from this work. The error bar on our AP flux densities indicates our $\sim$50% uncertainty. The figure shows that both APs and GPs have lower flux density below $\sim$100 MHz. GPs from PSR B0950+08 {#gps0950} --------------------- The cumulative distribution of pulses with flux density 10 times larger than that of the AP ($S_{\rm AP}$) was found to follow a power law $N(>S/S_{\rm AP})\propto S^\zeta$, where $\zeta=-4.09$ and $-5.06$ for 42 and 74 MHz respectively, as shown in Figure \[loglogGpsEventRate0950\]. This supports our use of the definition of GPs as 10 times the AP’s flux density for PSR B0950+08 as found in @2012AJ....144..155S. The strongest GP at 42 MHz had a flux density 29 times larger than the APs, while at 74 MHz the strongest one was found to be 24 times larger. The cumulative distribution of pulse strength for 42 and 74 MHz has a steeper power-law for the GPs than found by @2012AJ....144..155S for 103 MHz and @2012ARep...56..430S for 112 MHz. All these results indicate that PSR B0950+08 is weaker, and produces less frequent and less intense GPs at low frequency than at 100 MHz. All GPs have double peaked structures and the phase of GPs drifts through the range of the AP profile, as shown in Figure \[phasesingledouble0950\]. If each GP is an independent event with a uniform probability for pulse generation at any given time, we expect the distribution of intervals between GPs to exhibit an exponential functional dependence. For simplicity, we will use the number of accumulated pulse periods, $p$, as a time measure. Then, the interval distribution for a single event as a function of the number of periods is given by $$I_1(p) = r\ \mbox{exp}(-r p), \label{eqn:exponential distribution}$$ where $r$ is the average event rate (GPs per period). The observed distribution is shown in Figure \[intervaldistribution\], which indicates that the GPs are indeed independent events. Scattering Analysis {#sect:scattering} =================== We made use of the CLEAN-based algorithm [@2003ApJ...584..782B] to analyze the scattering effect on the temporal broadening of the GP and AP from the PSR B0950+08. The observed pulses are composed of the intrinsic pulse convolved with propagation effects and instrumental response. The CLEAN-based algorithm utilizes an accumulated delta-like signal to restore the intrinsic pulse. This approach allows for the deconvolution of various profile shapes without knowledge of the intrinsic profile. The recorded signal $P_{obs}$ is $$P_{obs}(t) = I(t)\otimes pbf(t)\otimes r(t), \label{convolutions}$$ where $I(t)$ is the intrinsic pulse profile, $pbf(t)$ is the pulse-broadening function and $r(t)$ is a function which gives the combined instrumental responses including effects due to data reduction. We applied this algorithm to data from the LWA Pulsar Data Archive [@2014arXiv1410.7422S] for observations from 25 to 75 MHz and the EPN data archive for 102 MHz to 10.6 GHz, and this work. We include as part of the instrumental responses the effect derived from setting the bin size of the time series to be same as the temporal resolution and a similar effect for the frequency channel width. For simplicity, we compare only the scattering time constant from a thin screen model for APs in Figure \[figallB0950+08\] with results for pulses with SNR$>7$. After deconvolution we found the exponential decay time in the thin screen scattering module from pulses with SNR$>7$ centered at 42 and 74 MHz indicate a frequency scaling index of $-1.45\pm0.14$ which differs to $-0.91\pm0.2$ calculated from the APs. And over a much wider range of frequencies, see Figure \[figallB0950+08\] and \[B0950+08spectralindex\], is $-0.14\pm0.03$, which also greatly differs from of pulses with SNR$>7$. However, scatter-broadening should be a property of the ISM through which the pulse is traveling, and therefore should be the same for all types of pulses from a given pulsar. So the inconsistent exponential decay time we had from pulses with SNR$>7$ (2.5$\pm1.3$/1.1$\pm0.7$ ms for 42/74 MHz) and AP (5.4/3.4 ms for 42/74 MHz) should be resulted from the dominated evolution of the profile at different frequencies, such as radius-to-frequency mapping [@1978ApJ...222.1006C], rather than the scattering effect from ISM. Also as @2013MNRAS.434...69L [@2015ApJ...804...23K] argue one can obtain reliable values of scatter time (from any method) only when the scatter time is significantly larger than the width of the profile. The exponential decay time derived from CLEAN method is much smaller than the profile width. So the ISM scattering effect still is not strong enough to be distinguished when the frequency is down to 42 MHz within line of sight to PSR B0950+08. Pulse Emission Altitude {#sect:altitudes} ======================= Observations of GPs can be used to probe a pulsar’s emission region. This can be done in a more subtle fashion if simultaneous observations at different frequencies are taken for a given pulse. Of particular importance is the observed separation in time between the two peaks in a GP or AP profile at the two observing frequencies. We consider the difference in the the altitude of emission at the two observing frequencies. We do this both for APs and GPs and find a similar difference in emission altitude between the two frequencies. In analyzing the difference in the altitude of the emission region for the two frequencies observed we made use of the dipolar magnetic field model, as discussed in @2012hpa..book.....L. We will briefly summarize the basic features of this model that were used to calculate the altitude difference. In the dipolar magnetic field model the field geometry is described using polar coordinates such that the ratio between $\sin^2 \theta$ and a radius ${r}$ is fixed along a given magnetic field line. So, we can connect a point at $(r, \theta)$ along the last open field line of a dipole at the radius of light cylinder $r_{LC}$ by $$\frac{\sin^2\theta}{r} = \frac{\sin^2 90^\circ}{r_{LC}}. \label{dipoleradius1}$$ The opening angle $\rho$ is the half-width of the beam; it can be related to $\theta$ as $$\tan \theta = -\frac{3}{2\tan\rho}\pm \sqrt{2+\frac{9}{4 \tan^2\rho}}. \label{dipoleradius2}$$ if the emission cone is confined by the last open magnetic field line [@2001ApJ...555...31G]. From equations (\[dipoleradius1\]) and (\[dipoleradius2\]), the opening angle $\rho$ can be related to the emission height $r$ as $$\rho = 86^\circ \left(\frac{r}{r_{LC}}\right)^\frac{1}{2}, \label{dipoleradius3}$$ using the small-angle approximation for both $\rho$ and $\theta$. The opening angle is also related to the observed pulse component separations $\Delta\phi$ as $$\cos \rho = \cos \eta \cos (\eta+\psi) + \sin(\eta)\sin(\eta+\psi)\cos\left(\frac{\Delta\phi}{2}\right), \label{dipoleradius4}$$ where $\eta$ is the angle between rotation and magnetic axes, and $\psi$ is the impact parameter, which is the angle of closest approach of the magnetic axis and the line-of-sight to the observer. Given the component separations $\Delta\phi=19^\circ\pm0.75^\circ$ and $12.5^\circ\pm0.54^\circ$ at 42 and 74 MHz respectively for the APs from Figure \[phasesingledouble0950\] and $\eta=5.9^\circ$ and $\psi=-4.2^\circ$ for PSR B0950+08 from @1988MNRAS.234..477L, we find that the emission altitudes of both frequencies are $r$(42 MHz) = 29267$\pm36$ m ($\approx0.242\%$ of $R_{LC}$) and $r$(74 MHz) = 29013$\pm17$ m ($\approx0.240\%$ of $R_{LC}$), and the altitude difference is 254$\pm53$ m. For GPs, given the component separations as 15.2$^\circ\pm0.30^\circ$ and 10.3$^\circ\pm0.13^\circ$ for 42 and 74 MHz respectively, the altitude is 29106$\pm11$ m ($\approx0.241\%$ of $R_{LC}$) and 28950$\pm3$ m ($\approx0.240\%$ of $R_{LC}$) for 42 and 74 MHz respectively, and the altitude difference is 156$\pm14$ m. Because the uncertainties are not available on $\eta$ and $\psi$ from @1988MNRAS.234..477L, the uncertainties noted above in altitudes $r$ are solely calculated from uncertainties of $\Delta \phi$. The emission altitudes of APs are within generally accepted $10\%$ of the $R_{LC}$ and are much closer to the surface of the pulsar than to the light cylinder. The mean emission altitudes of GPs are a little closer to the surface of the pulsar than APs for both 42 and 74 MHz. There are studies shows a variety ratios of emission altitude to light cylinder of GPs, such as GPs of PSR J1823$-$3021A are emitted no higher than 4 km above ordinary emission [@2007MNRAS.378..723K], or GPs of PSR B1821$-$24A are speculated to have emission altitudes near the light cylinder where is much different from the regions of radio emission is placed traditionally[@2015ApJ...803...83B]. As we can see from panels (b) and (c) in Figure \[phasesingledouble0950\], the weaker GPs have broader range of phases. The stronger GPs appear to concentrate toward the maximum intensities of components. This was also indicated by @2006ARep...50..915S with analysis of this pulsar at 111 MHz. Note that the mean peak separation is less for the GPs than the APs. Conclusion {#sect:conclusion} ========== We observed PSR B0950+08 simultaneously at 42 and 74 MHz detecting GPs and APs. Our study shows GPs and APs from PSR B0950+08 are much weaker than at $\sim$100 MHz. This indicates a turn-over in the spectrum of GPs between 74-100 MHz which is consistent with previous observations [@2015AJ....149...65T]. We analyzed the effect of scattering using the CLEAN-based algorithm [@2003ApJ...584..782B] and found that the scattering effect still can not be observed for frequency down to 42 MHz. There are other effects that dominated the profile broadening, rathe than the scattering effect from the ISM. We determined the emission altitude in the context of a dipolar magnetic field for our set of observations for both GPs and APs. We found $r$(42 MHz) = 29.27 km ($0.242\%$ of $R_{LC}$) and $r$(74 MHz) = 29.01 km ($0.240\%$ of $R_{LC}$) for the average pulse, while for giant pulses, $r$(42 MHz) = 29.10 km ($0.241\%$ of $R_{LC}$) and $r$(74 MHz) = 28.95 km ($0.240\%$ of $R_{LC}$). The difference in emission altitudes of GPs is similar to that of the APs. Most GPs can only be detected at one frequency which implies that the emission of GPs is localized within a small region and drifts within the emission region of the APs. The average component separation of the GP is smaller than that of the AP, and the GP’s component separations are closer to the average with larger intensity. Acknowledgments {#acknowledgments .unnumbered} =============== We acknowledge insightful discussions with Kevin Stovall and Roger Link. Construction of the LWA has been supported by the Office of Naval Research under Contract N00014-07-C-0147. Support for operations and continuing development of the LWA1 is provided by the National Science Foundation under grant AST-1139974 and AST-1139963 of the University Radio Observatory program. The computation is supported by the Advance Research Center of Virginia Tech. Data reduction was performed using the BlueRidge system at Virginia Tech. [Facility:]{} natexlab\#1[\#1]{} , Z., [Nice]{}, D. J., [Taylor]{}, J. 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PSR B0950+08 passed the meridian at 120 minutes after the first observing frame, with an altitude = 63.85$^\circ$. The two panels demonstrate the sensitivity dependence on a target’s zenith angle and the observing frequencies of LWA1 in beam-tracking mode. We corrected for these systematic effects when calculating the intensity of GPs. Each data point is the 24-minute averaged intensity. There are three observations from different dates in each panel. []{data-label="altitudecorr"}](f1.eps "fig:"){width=".45\textwidth"} ![The flux density at different altitudes at two frequencies. PSR B0950+08 passed the meridian at 120 minutes after the first observing frame, with an altitude = 63.85$^\circ$. The two panels demonstrate the sensitivity dependence on a target’s zenith angle and the observing frequencies of LWA1 in beam-tracking mode. We corrected for these systematic effects when calculating the intensity of GPs. Each data point is the 24-minute averaged intensity. There are three observations from different dates in each panel. []{data-label="altitudecorr"}](f2.eps "fig:"){width=".45\textwidth"}\ ![The AP profiles and GP peak phases at two frequencies. Panels (a) and (d) show the profile of the AP at each frequency, the three dash lines are Gaussian fit to the profile using a least squares fitting algorithm. The red solid curve is the summation of three Gaussians. Panels (b) and (c) show GP peak phases and flux density at each frequency compared to the flux density of the AP. A GP is defined as a pulse with flux density ratio ($S/S_{\rm AP}$)$>$10 in this study. The pulsar’s period is 253.06 ms. []{data-label="phasesingledouble0950"}](f3.eps){width=".75\textwidth"} ![The spectra of pulse widths observed for PSR B0950+08 normalized to the period of $360^{\circ}$. The pulsar’s period is 253.06 ms. We fit the spectral index for two frequency ranges, separated at 410 MHz. The vertical error bar is one sigma assuming Poisson statistics unless otherwise specified in references for the observations cited. Observations are from @2015AJ....149...65T:39.4 MHz; @1971ApJS...23..283M:0.41 GHz, 1.665 GHz; :2.7 GHz, 4.9 GHz; @1979SvA....23..179I: 61 MHz, 102.5 MHz; @1981AJ.....86..418R: 430 MHz; : 4.6 GHz, 10.7 GHz; @1992ApJ...385..273P: 25 MHz, 47 MHz, 112 MHz, 430 MHz, 1408 MHz, 4800 MHz; : 45 MHz and this work: 42 MHz, 74 MHz. []{data-label="pulsewidthindex"}](f4.eps){width="75.00000%"} ![Observed flux densities for PSR B0950+08 for different observing frequencies are shown here. The AP flux density data points have 50% error bars unless otherwise specified in references for the observations cited. The vertical line indicates the range of GP values. The thin error bars extending above and below indicate the 50% error associated with the lowest GP and highest GP flux density. The black solid square represents the flux density for the AP. Red halo circles are the AP flux densities for LWA1 at 42 and 74 MHz (this work). The thick red vertical line indicates the range of GPs’ values. The black halo square represent previous LWA1 observation at APs and GPs by @2015AJ....149...65T at 39.4 MHz. Blue down triangle and green up triangle similarly represent observations by [@2012AJ....144..155S] at 103 MHz, and by @2012ARep...56..430S at 112 MHz respectively. The AP observations (black squares) are from (left to right: points 1–3, [@2013MNRAS.431.3624Z]; points 4–6, and 9, [@GouldLyne]; point 7, 10, and 12, [@Seiradakis]; points 8 and 11, [@vonHoensbroechXilouris]. The dashed black line is a fit through the AP observations, of spectral index $-$2.2. []{data-label="fluxspectra0950"}](f5.eps){width="75.00000%"} ![The cumulative pulse number $N(>S/S_{\rm AP}$) plotted versus flux density. The red dashed line in both panels is the power-law fit for $S/S_{\rm AP}>$10. []{data-label="loglogGpsEventRate0950"}](f6.eps){width="75.00000%"} ![GP interval distributions at both frequencies. Intervals on the horizontal axis are in units of 100 periods. The rate shown is the slope of a fit from 0 to 2800 periods and 0 to 1900 periods for 42 and 74 MHz, respectively. We did not find interesting clustering or periodic behaviors regardless of the chosen binning interval. []{data-label="intervaldistribution"}](f7.eps){width=".75\textwidth"} ![Profiles for different observing frequencies. The data with frequency range from 25 to 75 MHz are from LWA Pulsar Data Archive [@2014arXiv1410.7422S], the rest are from European Pulsar Network (EPN) data archive with contributors:, and . Profiles are aligned with the phase of the maximum. []{data-label="figallB0950+08"}](f8.eps){height=".75\textwidth"} ![The exponential decay time $\tau$ of the profiles derived from the CLEAN-based method, assuming a thin screen model. The derived spectral index is $\alpha = -0.14\pm$0.03 for $\tau\propto\nu^\alpha$. Data used here are as same as in Figure \[figallB0950+08\]. []{data-label="B0950+08spectralindex"}](f9.eps){height=".75\textwidth"}
Q: Vue.js: How to show loading statement instead of white page before application loads When a new Vue.js page is opened, a white page appears for a while until the whole application loads. I tried many times to put the loading statement first with the traditional way, but the problem is that even the loading statement needs a while to load and appear, to replace the white page. <div id="app"> <template> <div id="app"> <v-app> <navbar></navbar> <v-content class="mx-sm-12 mt-8 mx-1"> <router-view /> </v-content> </v-app> </div> </template> <script> import navbar from "./components/navbar"; export default { components: { navbar } } </script> A: Your html will be downloaded and render first. you should have your loading in the index.html. After the JS (Vue built file) downloaded it will replace the <div id="app"></div> in your index.html. I solved this loading by having my index.html like this: <html> <head> ... </head> <body> <div id="app"> <div id="loading__container"> <div>some animation and text to indicate loading...</div> </div> </div> <style> #loading__container { // animation style } </style> <script type='text/javascript'> var loading = document. getElementById("loading__container") // ... do things with the loading container </script> </body> </html>
Nancy Andrews (actress) Nancy Andrews (December 16, 1920 – July 29, 1989) was an American stage and film actress and singer. Biography Nancy Andrews was born in Minneapolis, Minnesota, on December 16, 1920. Her parents were James Currier Andrews and Grace Ella Andrews (née Gerrish). She attended Beverly Hills High School and the Los Angeles City College. She also studied at the Pasadena Playhouse and the American Shakespeare Academy. Stage work Nancy Andrews started her career as a cabaret singer and pianist. Her first stage appearance was in 1938 in a production of The Merry Wives of Windsor at the Beverly Hills Shakespeare Theatre. From 1943 through 1945, she performed with the United Service Organizations. Andrews made her Broadway theatre debut in 1949 in the revue Touch and Go at the Broadhurst Theatre, a performance for which she won a Theatre World Award. In 1954, Andrews toured Europe in the one-woman show Songs and Laughter. In January 1955 she appeared in the original production of Plain and Fancy and later that year in Pipe Dream. In 1962 Andrews co-starred with Sid Caesar and Virginia Martin in the Broadway musical Little Me, playing Old Belle. Andrews appeared at the 1969 Dublin Theatre Festival in a production of In the Summer House. Film work Nancy Andrews appeared in several films including The Werewolf of Washington and Summer Wishes, Winter Dreams in 1973, W.W. and the Dixie Dancekings in 1975, and Night of the Juggler in 1980. She also appeared on various talk shows such as The Ed Sullivan Show (then referred to as Toast of the Town), The Perry Como Show, The Joe Franklin Show and The Merv Griffin Show. Andrews was a member of the National Academy of Television Arts and Sciences. Death On July 29, 1989, Andrews died of a heart attack at the age of 68 at the St. John's Hospital in Queens. References External links Category:1920 births Category:1989 deaths Category:American stage actresses Category:American film actresses Category:Theatre World Award winners Category:Actresses from Minneapolis Category:20th-century American actresses
Update: Drugs Found on Maersk Alabama After Two Die Onboard By The Maritime Executive 02-21-2014 10:42:00 Traces of narcotics and hypodermic needles have been found with the bodies of two American security officers on the container ship Maersk Alabama, a Seychelles government official has stated. Background: Two Dead on Captain Phillips' Ship [Updated] Police said an autopsy would be carried out early next week. However, the unidentified Seychelles government official said that the presence of drug traces and paraphernalia would suggest that their deaths were a result of drug overdose. A Seychelles police statement said that despite media accounts of traces of drugs, authorities have not released any reports suggesting the deaths were the result of an overdose. The statement, however, did not deny that drugs were found or suggest an alternative cause of death. Thomas Rothrauff, President/CEO of Trident Group – the maritime security company who employed the two deceased ex-Navy SEALs – released the following statement: “It is with great sorrow that Trident Group confirms the death of two Security contractors while onboard a merchant vessel which was pier side in the Seychelles. Seychelles authorities are conducting a full investigation of the circumstances surrounding the incident. There is no immediate indication as to the cause of death, but the deaths were not caused by operational activity. The next of kin have asked that no further information be released and requested that all respect the privacy of the families.” Shipping giant Maersk, which hired the Trident Group to guard its ships, said that Trident would be conducting random drug tests of its employees. The statement also said that Maersk and Trident have a history together, and this is an isolated incident. Nonetheless, new drug tests would start immediately and the company's shore-leave policy was under review. A U.S. Coast Guard spokesman said the service was investigating the deaths, as required by U.S. law. He said the deaths do not appear to be criminal in nature, related to vessel operations, the material condition of the ship or their duties as security personnel.
Roundup of Aerospace and Defense Forecasts and Market Estimates for 2013 Staff Writer Sept. 05, 2013 Modern Manufacturing The paradox of how much to spend on national defense and security versus social programs is a challenge all nations are facing today. Emerging economies are projected to be the most adept at managing this paradox. However, given their relatively higher levels of gross domestic product (GDP) growth versus their slower-growth (and often larger) counterparts — and once you consider that many of these countries have aerospace programs and initiatives planned or already in place — the paradox becomes even more challenging. Investing in Aerospace Drives Innovation Aerospace programs have perennially proven to be one of the most powerful sources of innovation any nation can invest in, and it is encouraging to see spending stabilize and even grow in certain nations. Investing in aerospace augments and strengthens national competitiveness by serving as a strong catalyst for both innovation and discovery, as well as a component of national defense. The Era of Cyber Warfare Has Arrived The United States is one of the world’s leaders in cyber deterrents and cyber warfare technologies, with the 2014 federal budget showing this area as a high priority for future investment. China’s Defense Ministry reported that during 2012, they averaged 144,000 attacks a month on their servers and online systems and have increased spending on their cyber warfare command centers as a result. In 2009, South Korea reported 95,000 daily hacking attacks against military computer networks. Russia’s cyber polices have for years led to separate line items in their national budget specifically for cyber warfare. High-income economizing nations lead the world with 75 percent of all countries having active military cyber programs in place. The high-income spenders — a category that includes Israel, Kuwait, Singapore, the United Arab Emirates and the United States — lead the world in spending, yet only 40 percent of these nations have military cyber programs. Here are a few key takeaways from recent aerospace and defense (A&D) cloud computing forecasts, as well as market estimates: According to IBM, the global aerospace and defense market reached a value of $674.6B in 2008; the company forecasts this figure to increase to $910B in 2013, attaining a year-over-year increase of 6.17 percent. That means 70 percent of spending will be in defense. The report also shows that the role of the original equipment manufacturer (OEM) has shifted drastically in A&D, with horizontal systems integrators comprising their primary mission. The highly diverse nature of A&D supply chains is driving this revolutionary shift in how OEMs are managing suppliers, outsourcing and design processes. The changing nature of A&D supply chains is also reflected in the latest study by Alix Partners, showing the migration to tier 2 and 3 suppliers and small supplier bases overall. This market dynamic favors the adoption of cloud computing through A&D value chains. IBISWorld is forecasting that commercial spending on aircraft, engine and parts manufacturing will continue to accelerate and eventually outpace defense spending. In the IBISWorld report Aircraft, Engine & Parts Manufacturing in the U.S., revenue is projected to reach $186.3B in 2013, sustaining a 1.8 percent compound annual growth rate (CAGR) through 2018, generating $42.5B in profits. The following graphic is an analysis of the distribution of products and services revenue as of this year. IBISWorld is forecasting the majority of commercial aircraft, engine and parts manufacturing in 2013 will be exports (54.7 percent), followed by wholesalers (18.6 percent) and the U.S. government (14 percent). Take a look at their graphical breakdown of the market segmentation for 2013 sales of $186.3B. Boeing is the U.S. market leader in the field of aircraft, engine and parts manufacturing, with 30.5 percent market share; they are followed by United Technologies (12.2 percent), Lockheed Martin (8.3 percent) and Northrop Grumman (5.9 percent). In this report, independent investment advisory company Methorios Capital S.p.A. predicts that robotic/drone systems will be the highest growth area of A&D spending in 2014 with a 55 percent CAGR, followed by cybersecurity (46 percent) and autonomous vehicles (42 percent). Methorios Capital S.p.A. has also found that at 60 percent market share, the U.S. is the largest segment of the A&D market, followed by Europe (34 percent) and Asia-Pacific (APAC) at 6 percent. They’re also forecasting a $1.65 trillion market for global defense spending in 2016, and a key assumption is that APAC will lead overall market growth. According to Alix Partners, APAC will also lead A&D spending, with China being the highest-growth market overall, as the following graphic illustrates. Are you surprised by any of these research findings or predictions? What would you add to the list?
This invention relates to fitted sheets, and specifically to adjustable fitted sheets which are maintained in position primarily by portions of the sheet bearing against the sides and bottom of the mattress rather than against the corners of the mattress. While this invention will be described primarily in connection with mattresses, and specifically spring and water bed mattresses, it will be understood that the sheet of this invention may be employed with various other types of cushions, such as pillows, sofa cushions and the like. The normal unfitted or flat bed sheet, when used as the bottom sheet to cover a spring bed mattress, has many advantages in that it is adaptable to various size mattresses, may be positioned on the mattress in any of four directions, and may be installed on the mattress one side at a time without the necessity of lifting any portion of the mattress since the sheet edges may be merely folded or tucked in between the mattress and the springs. This later advantage is especially useful in hospitals where it is undesirable to discomfort the patient by lifting the corners and edges of the mattress, such as is necessary with the common contoured sheet. Flat bed sheets, however, are easily pulled out of position during the normal tossing and turning of a person sleeping on a bed. Such sheets consequently become wrinkled after a short period of time creating discomfort and, in hospital situations, causing bed sores. The contoured bed sheets seek to overcome some of the problems of the flat sheet by elastic sewn around the top and bottom of the sheet and extending around all four corners. In order to install a contoured bed sheet on a spring mattress, three corners of the sheet are normally fitted around the first three mattress corners and the fourth corner of the mattress is then lifted to a substantial height in order to place the fourth corner of the sheet around the fourth mattress corner. Upon allowing the mattress to resume its original position, the contoured sheet is stretched tight across the top of the mattress and also at the corners, thus maintaining the sheet in a stretched or taut position for the normal period of time between washings. The contoured sheet has various disadvantages, however, since the tension created by the dimensions of the sheet and the elastic accelerates sheet wear to such an extent that the corners of the sheet frequently rip and the elastic wears out and shrinks before the normal life of the sheet fabric. In addition, the necessity for lifting at least one corner of the mattress to a considerable height when installing the sheet makes the contoured sheet particularly unsatisfactory for use in hospitals and the like. Furthermore, tension created across the top of the mattress by a contoured sheet diminishes the full capacity of the mattress. For example, some mattresses are constructed with an abundance of coil springs in order to allow the mattress to conform to the body contour of the person sleeping on the mattress. If a contoured sheet is installed on such a mattress, the mattress will be placed under tension which tends to curl the corners and edges of the mattress upwardly and inwardly and to create stresses in the mattress which its designers did not intend. Such a prestressed mattress will not operate as intended and will thus deprive its owners of some of the benefits for which it was purchased. Such contoured sheets are also extremely awkward to fold and store due to the permanently crimped corners and the action of the elastic. Water bed mattresses have presented a particular problem to the bedding industry. These mattresses are a generally rectangular rubber or plastic container with a substantially rounded nose around the sides and at the corners instead of square sides and corners. When such a mattress is filled with water, it generally raises to a height of about ten inches. A normal fitted sheet is extremely unsatisfactory as the bottom sheet on a water bed mattress since it will be pulled loose from underneath the mattress in an extremely short period of time by displaced water pushing outwardly towards the mattress corners when a person sits or lies on the water bed. This displaced water hits against the corners of the mattress while at the same time the top surface of the mattress is placed under tension which tends to raise the corners of the mattress. Concurrently, the overlying sheet is placed under tension by the person sitting or lying on the bed. These stresses combined with the raised mattress corners eventually result in either tearing the corners or quickly loosening the sheet or both. In an attempt to solve this problem, regular contoured sheets have been modified to provide deeper corners or pockets to accommodate water bed mattresses which are approximately ten inches high, whereas regular spring mattresses are only about seven inches high. These contoured sheets have not solved the problem, however, since if they do remain in place on the mattress corners, the pressure against the sheet corners by the displaced water action described above causes the sheet corners to tear after a very short period of time. In any event, the sheet corners usually come loose from the mattress corners and thus these sheets continue to possess both disadvantages, that is, the sheet corners are subjected to stress until the sheet corners tear or come loose or both. The top sheet commonly sold with contoured water bed bottom sheets is sewn to the foot of the contoured sheet, thus forming an expensive combination which must be washed, folded and stored together. In addition, since the bottom contoured sheet usually wears out extremely quickly, and certainly before the normal life of the sheet fabric, both the top and bottom sheet are rendered inoperative at an early stage. The present invention overcomes the disadvantages of the prior art flat and contoured sheets by providing a fitted bottom sheet which has adjustable corners securely retained over the mattress corners while at the same time eliminating stress against the sheet corners and across the top sleeping panel of the sheet which might detract from the operability of the mattress. In its application to water beds, the bottom fitted sheet of this invention provides an aperture at each corner through which a portion of the water bed corners protrude so that the stresses transmitted to the water bed mattress corners by activity upon the mattress is not transferred to the sheet corners. Furthermore, the corners of this sheet are adjustable to accommodate various mattress dimensions while at the same time the sheets may be folded relatively flat for easy packaging and storage. In addition, these sheets are easily installed by merely folding portions of the sheet underneath the mattress without the necessity of raising the mattress to a substantial height, thus rendering this sheet particularly suitable for use in hospitals and the like. Due to the lack of tension at the corners and across the top of the sheet of this invention, this sheet will not rip or tear during use so that the full life of the sheet material may be enjoyed. The adjustability of this sheet provides an actual reduction in the amount of material and number of sheet sizes required to fit the different size mattresses presently on the market. For example, a normal flat queen size sheet, when constructed in accordance with teachings of this invention, will fit a water bed mattress, an eastern king size mattress, and the western king size mattress. A normal flat double bed size sheet, when constructed in accordance with the teachings of the invention, will fit a queen size mattress, a double bed size mattress and a sofa or hide-a-bed mattress. A flat twin size sheet, when constructed in accordance with the teachings of this invention, will fit all twin bed size mattresses from 36 to 39 inches in width. Such a reduction in the number of sheets and the size of the sheets required to fit the mattresses on the market will result in a great savings in both material and fabrication costs. In addition, this invention may be employed on blankets, bedspreads, bed pads, and the like.
Sixteen players will begin pre-season training at Melwood on Saturday. Liverpool’s preparations for 2019-20 are set to get under way in West Derby this weekend as the champions of Europe regroup for the new campaign. Jürgen Klopp and his coaching staff will have the following 16-man squad of players to work with on the opening day – which you can follow with comprehensive coverage on Liverpoolfc.com. Arroyo, Brewster, Clyne, Fabinho, Gomez, Kent, Hoever, Jones, Lallana, Matip, Milner, Oxlade-Chamberlain, Phillips, Van den Berg, Wilson, Woodburn. Join us to watch every pre-season game on LFCTV and LFCTV GO. Go to www.liverpoolfc.com/watch for more information and to see the live rights in your country.
library TestCompatibilityLevel3 define Test: timezone from @2020-02-01T10:30:00.0Z
Optimisation of the derivatization in cellulose-type chiral selectors for enantioseparation by centrifugal partition chromatography. Cellulose was chemically modified with hydrophobic dodecanoyl groups followed by 3,5-dimethylphenylcarbamoyl substituents forming mixed ester/carbamate derivatives in order to improve the solubility in lipophilic solvents compared to the corresponding homosubstituted cellulose tris(3,5-dimethylphenylcarbamate). Two mixed derivatives of different degree of substitution were prepared, tested as chiral selectors (CSs) in counter-current chromatography (CCC) and compared to the homo-substituted derivative. Alternatively, cellulose tris(3,5-dichlorophenylcarbamate), was synthesised and tested with the same purpose. The racemic drugs pindolol and warfarin were used as test compounds. Biphasic organic/aqueous solvent systems, composed of methyl isobutyl ketone, t-butyl methyl ether or ethyl acetate and aqueous ammonium acetate or sodium phosphate buffer, were used. Centrifugal partition chromatography, a variety of CCC, in the classical elution mode and the pH-zone-refining displacement mode was applied. The enantioseparation of pindolol and warfarin was achieved in the latter conditions. The presence of dodecanoyl chains on the CS increased solubility in the organic solvents used. The selectivity of the mixed dodecanoyl/3,5-dimethylphenylcarbamoyl cellulose derivative with low degree of dodecanoyl groups (degree of substitution 0.3/degree of substitution 2.6, respectively) was similar to that of the homo-substituted derivative. Furthermore, the loading capacity for pindolol was increased by a factor of three compared to cellulose tris(3,5-dimethylphenylcarbamate). Nevertheless, the increasing degree of substitution with dodecanoyl groups on the CS, although improved solubility in the stationary phase, contributed negatively to the enantioselectivity, where warfarin was more affected than pindolol.
I was gifted one and was wondering if someone had a guesstimate of the wind load sq ft of this beast. The ~center 18ft of the boom is 3.5" dia, .25" wall+ and 3" thinner wall from there out. The elements taper from 1.625 to .875. Mike, K4EAR _______________________________________________ _______________________________________________ TowerTalk mailing list TowerTalk@contesting.com http://lists.contesting.com/mailman/listinfo/towertalk
Product Overview Main Features (v. 6.0) license + 1 Year Essential Support 1 user Symantec Buying Programs : Express level D (100-249) Symantec Protection for SharePoint Servers detects and removes viruses, spyware, and other threats on files uploaded to and downloaded from your SharePoint server(s). Using Symantec's antivirus technologies it quickly scans files for potential threats. The product integrates into the SharePoint Administration Console to provide easy and seamless management of your SharePoint server environment.
The Nuclear Crisis Group aims to offer advice in real time to Trump’s team and leaders of other governments to take steps to avoid escalation and make a nuclear exchange less likely. \| AP Photo Ex-nuke commanders launch ‘crisis’ group to educate Trump A global coalition of former military leaders and diplomats who had responsibility over nuclear weapons is launching a "shadow security council" to offer advice to world leaders on how to reduce what they consider to be the growing danger of a nuclear conflict fueled by the rhetoric of President Donald Trump and destabilizing moves by Russian President Vladimir Putin. The Nuclear Crisis Group, which will be announced in Vienna on Friday, boasts nearly two-dozen members of the nuclear priesthood of at least eight major nations — including a former commander of the U.S. atomic arsenal; the former chairman of the Joint Chiefs of Pakistan; a retired admiral who was in charge of India's nukes; the ex-heads of the Chinese military's strategic studies and science institutes; and Russia's former foreign minister and chief atomic weapons designer. Others joining the initiative include Thomas Pickering, the United Nations ambassador under George H.W. Bush who also served as ambassador to Russia, India and Israel. Their aims include offering public and private advice in real time to Trump’s team and leaders of other governments in the hope their collective credentials will make officials listen — and take concrete steps to avoid escalation and make a nuclear exchange, whether accidental or on purpose, less likely. "Not only is the U.S.-Russia relationship on much more shaky ground but the whole political environment has deteriorated," said Richard Burt, the chief negotiator for President George H.W. Bush in the 1991 Strategic Arms Reduction Treaty with Moscow and one of the leaders of the group. He cited recent tensions with North Korea, an unchecked nuclear arms race between India and Pakistan, and China's steady nuclear buildup — all at a time when a vacuum of expertise and understanding on the nuclear threat exists, both within the U.S. and foreign governments and among the public. "The issue of nuclear weapons has strangely kind of receded from people's consciousness," Burt said in an interview. "We must remind people in these different crisis situations that there is a nuclear danger and it needs to be addressed. We can play a useful role in reminding both governments and publics of the dangers as well as the possible solutions." Several participants likened the effort to the "Track II" diplomacy often relied on during the iciest periods of the Cold War. Unlike negotiations that take place through official government channels, Track II relies on unofficial actors — often with high-level government backgrounds who still maintain influence — who can operate with less constraints to try to resolve conflicts behind the scenes. The new effort is an outgrowth of Global Zero, a nonpartisan campaign including 300 world leaders that was founded in 2007 to seek ways to rid the world of nuclear arms. The movement had a key supporter in President Barack Obama, who in 2009 called for a world free of nuclear weapons. But the momentum, which peaked with the 2011 New Start Treaty with Russia, has fizzled — and many say even reversed — as relations between Washington and Moscow, the two largest nuclear weapons powers, have reached a post-Cold War low. Derek Johnson, Global Zero's executive director, said that as a result the movement has been forced to refocus some of its focus on reducing nuclear stockpiles toward determining "what we can do to stop one of these things from going off." Several architects of the effort cited recent statements by Trump as one reason they felt the urgency to inject "actual facts" into the debate. In a stark departure from past presidents in both parties, Trump has called for building up the U.S. nuclear arsenal. He has claimed, to the dismay of generations of arms control expert, that the United States got a bad deal in the most recent nuclear arms reduction treaty with Russia. And he recently said there could be a war with nuclear-armed North Korea. Russian leader Vladimir Putin, meanwhile, has overseen a major nuclear buildup and permitted the Russian military to violate the Cold War-era Intermediate-Range Nuclear Forces Treaty by deploying a new nuclear-armed cruise missile. "There is a lot of rhetoric right now that is heightened," said retired Marine Corps Gen. James Cartwright, a former vice Joint Chiefs chairman during the Obama and George W. Bush administrations and who also ran the U.S. Strategic Command, which controls the nation’s nuclear missiles, bombers, and submarines. "The question is can you do something about it and keep it under control?" "Trump has introduced a level of volatility at a uniquely dangerous moment," Johnson said in an interview. Citing North Korea, Russia and other hot spots, he added: "Things are heating up but I think it is pretty clear he is not equipped to handle those flash points." Michael Short, a spokesman for the White House National Security Council, declined to address questions about the criticism or Trump's plans to reduce nuclear dangers. Johnson and others also see a lack of rigor on the nuclear weapons threat at all levels. "There's a real diplomatic and analytical vacuum that has to be filled," he said, citing proposed Trump administration cuts to the Department of State. "The State Department is a ghost town. It is hard to imagine a worse time to gut State." He said the new group will be meeting regularly and as crises are unfolding request meetings with key decision makers and publish options for reducing the chances of nuclear confrontation. Cartwright previewed a few proposals the group is already considering. They include finding ways to expand the decision time that leaders have to respond to a perceived nuclear escalation in order to avoid miscalculation; improving communication between nuclear powers; and seeking ways to defend against cyberattacks on nuclear command and control systems that could spin out of control. "All of those things that could lead you into an escalation you don't intend," said Cartwright. Morning Defense newsletter Sign up for Morning Defense, a daily briefing on Washington's national security apparatus. Email Sign Up By signing up you agree to receive email newsletters or alerts from POLITICO. You can unsubscribe at any time. This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply. Other recommendations could involve the redeployment of nuclear weapons so they are less likely to be used in a crisis and applying to North Korea the approach of the recent international pact to halt Iran's nuclear weapons program, according to Burt. Cartwright, who was pardoned by Obama after pleading guilty to lying to the FBI about press leaks of a U.S.-Israel cyberattack on Iran's nuclear program, said he hopes the group's collective voice of experience in these matters will offset any questions about his credibility. "We need savvy, independent, experienced experts to shine a spotlight on these dangers, speak truth to power, and make sure these flash points aren't catastrophically mishandled," Johnson said. "It's our goal to help to chart a course safely through to the other side. Part of that too is exposing these risks — focusing the press and the public on these dangers so governments can't ignore them or blunder into disaster — and ratcheting up pressure for diplomatic solutions. Warned Burt: "We are much closer into coming into conflict."
set(PACKAGE_NAME unit-striped-map) set(CMAKE_CXX_FLAGS "${CMAKE_CXX_FLAGS} -DCDSUNIT_ENABLE_BOOST_CONTAINER") set(CDSGTEST_STRIPED_MAP_SOURCES ../main.cpp cuckoo_map.cpp map_boost_flat_map.cpp map_boost_list.cpp map_boost_map.cpp map_boost_slist.cpp map_boost_unordered_map.cpp map_std_list.cpp map_std_map.cpp map_std_unordered_map.cpp ) include_directories( ${CMAKE_CURRENT_SOURCE_DIR} ) add_executable(${PACKAGE_NAME} ${CDSGTEST_STRIPED_MAP_SOURCES}) target_link_libraries(${PACKAGE_NAME} ${CDS_SHARED_LIBRARY} ${GTEST_LIBRARY} ${Boost_THREAD_LIBRARY} ${Boost_SYSTEM_LIBRARY} ${CMAKE_THREAD_LIBS_INIT} ) add_test(NAME ${PACKAGE_NAME} COMMAND ${PACKAGE_NAME} WORKING_DIRECTORY ${EXECUTABLE_OUTPUT_PATH})
Homeowner Below, you'll find a sampling of policy premiums for different amounts of coverage. If you have any additional questions or are ready to purchase flood insurance, you can contact an agent . Rates effective April 1, 2015 These PRP rates are for 1-4 Family Residential. Other residential building and contents coverage combinations are available. 1 Add a $25 HFIAA surcharge for policies covering primary residences only if the named insured's primary residence is a single-family dwelling, an individual condominium unit, or an apartment in a non-condominium building. Add a $250 HFIAA surcharge for all other policies. 4 Premium includes ICC Premium of $5 for residential coverage up to $230,000 and $4 for coverage over $230,000. Deduct this amount if the risk is a condominium unit. 5 Do not use this section of the table for buildings with crawlspaces or subgrade crawlspaces; see footnote 6. Use this section of the table if a building elevated on a crawlspace has an attached garage without openings. Note: Residential condominium associations are not eligible for the PRP. Individual residential condominium units in residential condominium buildings are eligible for the PRP. In addition, individual residential condominium unit owners in nonresidential condominium buildings are only eligible for contents coverage. The deductibles apply separately to building and contents. Building deductible, $1,000. Contents deductible, $1,000. To qualify for replacement cost claim settlement, a single-family dwelling must be the insured's principal residence and be insured to the maximum amount of insurance available under the program or no less than 80% of the replacement cost at the time of loss, whichever is less. Please refer to the Standard Flood Insurance Policy (SFIP) for further explanation and requirements. Rates in high-risk areas (A and V Zones) are calculated based on a variety of factors, including elevation and building construction. Policies can be purchased for contents only, building only, or both contents and building coverage. Talk to a licensed insurance agent to determine the premium for your specific property.
Q: Plot the Centroid of a Dataset in Matlab In matlab I have painted a figure with X1,Y1,Z1 axis using h=plot3(X1,Y1,Z1,'y'); And X1,Y1 and Z1 are row matrix with the shape. Now I want to highlight the point (x,y,z) consisting of the average of each row matrix in the same figure. How to highlight the average point in sharp or color and avoid being covered by row matrix point. I really want source program about matlab like plot3(). A: So you want to highlight the centroid of the cluster. You can do it with the following code. x1 = rand(10,1); y1 = rand(10,1); z1 = rand(10,1); plot3( x1, y1, z1, 'y' ); hold on; scatter3( mean( x1 ), mean( y1 ), mean( z1 ), 'r' ); hold off; You can use scatter3 to plot the point in red using the 'r' parameter. Circles are the best for this job and it won't be covered as it is hollow. You can use different colors or markers built into Matlab. Here are the results Unless you're plotting a trajectory, if you are plotting points, I suggest you use scatter3 instead of plot3. It gives the following plot. I would also suggest using blue instead of yellow for better visibility.
--- abstract: 'Lubricated surfaces have shown promise in numerous applications where impinging foreign droplets must be removed easily; however, before they can be widely adopted, the problem of lubricant depletion, which eventually leads to decreased performance, must be solved. Despite recent progress, a quantitative mechanistic explanation for lubricant depletion is still lacking. Here, we first explained the shape of a droplet on a lubricated surface by balancing the Laplace pressures across interfaces. We then showed that the lubricant film thicknesses beneath, behind, and wrapping around a moving droplet change dynamically with droplet’s speed—analogous to the classical Landau-Levich-Derjaguin problem. The interconnected lubricant dynamics results in the growth of the wetting ridge around the droplet, which is the dominant source of lubricant depletion. We then developed an analytic expression for the maximum amount of lubricant that can be depleted by a single droplet. Counter-intuitively, faster moving droplets subjected to higher driving forces deplete less lubricant than their slower moving counterparts. The insights developed in this work will inform future work and the design of longer-lasting lubricated surfaces.' author: - 'Michael J. Kreder$^{1}$' - 'Dan Daniel$^{1,2}$' - 'Adam Tetreault$^{3}$' - 'Zhenle Cao$^{3}$' - 'Baptiste Lemaire$^{1}$' - 'Jaakko V. I. Timonen$^{1,5}$' - 'Joanna Aizenberg$^{1,3,4}$' title: Film dynamics and lubricant depletion by droplets moving on lubricated surfaces --- [^1] [^2] Introduction ============ The ability of liquid lubricant on surfaces to reduce solid-solid friction has been widely known since antiquity [@harris1974lubrication; @fall2014sliding]; examples include the ubiquitous use of lubricant oil between the moving parts of a machine and the synovial fluid found naturally in the joint cavities of our bodies [@reynolds1886theory; @briscoe2006boundary]. The idea of using lubricant to reduce solid-liquid friction is relatively new: when infused with suitable lubricants, surfaces can exhibit excellent liquid-repellency [@quere2005non; @wong_SLIPS_2011; @lafuma_slippery_2011]. Such surfaces, known in the literature as Slippery Lubricant Infused Porous Surfaces (SLIPS), also show promise in various applications, including in biomedical devices and anti-ice materials [@sunny2016transparent; @leslie2014bioinspired; @kim_Ice_2012; @kreder_design_2016; @mistura2017drop]. The origin of repellency in SLIPS is largely due to the presence of a stable lubricant film above the solid surface; however, lubricant can be lost due to various factors (body forces, evaporation/solubility, shear, etc.), eventually leading to decreased performance [@wexler2015shear; @rykaczewski2013mechanism]. Many strategies have been proposed to retain the lubricant overlayer, ranging from the choice of structures (nanoscale vs. microscale, periodic vs. random, etc.) [@kim_hierarchical_2013; @kim2016delayed], to the choice of lubricant (high vs. low viscosity lubricant), and finally to the use of patterned wettability on a surface [@wexler2015robust]. Despite recent progress, a quantitative mechanistic understanding of lubricant depletion due to a moving droplet has not been reported in the literature. Here, we begin by using geometric arguments and quasi-static approximations—when balancing Laplace pressures across various interfaces—to deduce the shape of a droplet on a lubricated surface. We then proceed to establish scaling arguments for the dynamic behavior of lubricant around a moving droplet, by greatly expanding on the Landau-Levich-Derjaguin (LLD) analysis first outlined in @daniel_oleoplaning_2017 [@daniel_oleoplaning_2017]. We validated this model by using white-light interferometry to measure the dynamically-changing lubricant thicknesses behind, underneath, and wrapping around a moving water droplet. In our previous work, we showed that the LLD analysis can be used to model droplet mobility on lubricated surfaces [@daniel_oleoplaning_2017]. Here, we extend this analysis to directly model lubricant depletion and demonstrate the important role the wetting ridge plays, by showing explicitly that the wetting ridge (and its growth) is the dominant source of depletion. Results and Discussion ====================== ### Droplet geometry and Laplace pressures on SLIPS Recent work by @semprebon2017apparent and @tress2017shape used numerical methods to solve the Young-Laplace equation for the droplet geometry on a lubricant-infused surface [@semprebon2017apparent; @tress2017shape]. Our analysis is consistent with previous work, but we make a number of simplifying assumptions—for the case when the wetting ridge is much smaller than the droplet—that allow for an analytical solution and a simple physical interpretation for the geometry of a millimetric-sized droplet on well-designed SLIPS. ![image](Fig1_rev.png) As shown in Figure \[fig:geometry\]a, there are three important length-scales to consider: the external radius of the wetting ridge $r_{\text{ext}}$, the internal radius of the wetting ridge $r_{\text{int}}$, and the radius of the droplet itself $R$, whereby $r_{\text{ext}} \sim r_{\text{int}} \ll R$. Note that the micron thicknesses of the lubricant on the substrate outside the droplet, underneath the droplet, and wrapping around the droplet are much thinner than the size of the wetting ridge and do not directly affect the droplet geometry. In our schematic, there is a stable lubricant film underneath the droplet, meaning that there is no well-defined contact angle between the lubricant and the solid [@daniel_oleoplaning_2017]. While this is not always the case, the contact angle that the lubricant makes with the solid substrate is close to zero for many well-designed surfaces, even in the absence of a stable intercalating film [@schellenberger2015direct]. We begin by considering a droplet with a wrapping layer of lubricant over it, which occurs when the spreading coefficient of lubricant over the droplet is positive, that is $S_{ld} = \gamma_{dv}-\gamma_{lv}-\gamma_{ld}>0$ where $\gamma_{dv}$, $\gamma_{lv}$, and $\gamma_{ld}$ are the interfacial energies of the droplet-vapor, lubricant-vapor, and lubricant-droplet interfaces, respectively [@smith2013droplet; @schellenberger2015direct]. The geometry of the sessile droplet, ignoring the effects of gravity, can be understood by equating the Laplace pressures across the different interfaces in the system. The pressure in the drop $P_{\text{drop}}$ can be deduced by applying the Young-Laplace equation across the two interfaces of the wrapping layer, giving $$\label{eq:Pdrop} P_{\text{drop}} = P_{\text{atm}}+\frac{2 \gamma_{\text{eff}}}{R} = P_{\text{atm}} + \frac{2 (\gamma_{lv} + \gamma_{ld})}{R},$$ while the pressure in the wetting ridge can be deduced from the Laplace pressure either across the air-lubricant or lubricant-droplet interface, giving $$\label{eq:Pridge} \begin{split} P_\text{ridge} &= P_\text{atm}-\gamma_{lv} \left(\frac{1}{r_\text{ext}} - \frac{1}{a} \right) \\ &= P_\text{drop}-\gamma_{ld} \left(\frac{1}{r_{\text{int}}} + \frac{1}{a} \right), \end{split}$$ where $a$ is the base radius of the droplet. Comparing Equations \[eq:Pdrop\] and \[eq:Pridge\], and noting that $R\approx a$ for droplets with $\theta_{\text{app}} \approx 90 \degree$, which is true for water droplets on typical SLIPS, we find that $$\label{eq:CurveBalance} \frac{\gamma_{ld}}{r_{\text{int}}} = \frac{\gamma_{lv}}{r_{\text{ext}}}+\frac{\gamma_{lv}+\gamma_{ld}}{R},$$ where the droplet radius $R$ is set by the volume of the droplet $V$ and the apparent contact angle $\theta_{\text{app}}$ it makes with the surface, i.e. $V = \frac{\pi}{3} R^{3}(2 + \cos \theta_{\text{app}})(1 - \cos \theta_{\text{app}})^{2}$. To verify Equation \[eq:CurveBalance\], we imaged the wetting ridge using fluorescence confocal microscopy (Figure \[fig:geometry\]b) [@schellenberger2015direct]. We measured $R$, $r_{\text{int}}$, and $r_{\text{ext}}$ for droplets of 3 and 8 $\mu$l, and found good agreement (within 3 %) between values predicted from Equation \[eq:CurveBalance\] and experimental values (Supplementary Section S2 and Table S1). There has been some debate over the correct physical interpretation of $\theta_{\text{app}}$ for SLIPS, which is the angle observed using conventional optical contact-angle instruments [@schellenberger2015direct; @guan2015evaporation]. Interestingly, a lubricated surface approaches an idealized Young’s surface for a vanishingly small wetting ridge, since the there is no contact line pinning for an atomically smooth liquid-liquid interface. Hence, ${\theta_\text{app}}$ can be described by a modified Young’s equation: $$\label{eq:ContactAngle} \cos{\theta_{\text{app}}} = \frac{\gamma_{lv}-\gamma_{ld}}{\gamma_{\text{eff}}},$$ where the solid phase is replaced by the lubricant oil (l) phase and $\gamma_{\text{eff}} = \gamma_{lv} + \gamma_{ld}$ or $\gamma_{dv}$ for droplets with and without a wrapping layer, respectively [@semprebon2017apparent]. Equation \[eq:ContactAngle\] can be obtained by either minimizing energy or by balancing forces due to the interfacial tensions at the ridge, similar to argument originally proposed by Young [@young1805essay] (Supplementary Figure S1). Alternatively, ${\theta_\text{app}}$ can be deduced using purely geometrical considerations (Supplementary Figure S2). As shown in Figure \[fig:geometry\]c, there is good agreement between experimentally measured contact angles—both by this group [@wong_SLIPS_2011] and others [@schellenberger2015direct]—and the contact angles predicted by Equation \[eq:ContactAngle\] (See Supplementary Table S2 for data used in Figure \[fig:geometry\]c). Equations \[eq:CurveBalance\] and \[eq:ContactAngle\] are true only when $r_{\text{ext}} \ll R$ and $r_{\text{ext}} \ll l_{c}$, where $l_{c} = (\gamma_{lv}/\rho_{l} g)^{1/2} \sim$ mm is the capillary length for lubricant of density $\rho_{l}$. The wetting ridge is a low pressure region and it will grow in size until $r_\text{ext}\sim R$ or $r_\text{ext}\sim l_c$ as lubricant flows from the surrounding area into the ridge, analogous to the flow of liquid from the lamellae into the plateau borders in liquid foams [@cantat2013foams]. As the wetting ridge size grows and approaches $l_{c}$, it can no longer be approximated as an arc of a circle with radius $r_{\text{ext}}$, but is described instead by a Bessel function [@goodrich1961mathematical; @schellenberger2015direct]. In practice, for millimetric droplets on micron-thick lubricant films, the growth of $r_\text{ext}$ around a static droplet is limited by thin-film flow and does not approach $l_{c}$ even after a long time. For example, a 25 $\mu$l droplet sitting on 4 $\mu$m thick 20 cP silicone oil had a wetting ridge with an initial $r_\text{ext}\approx 50$ $\mu$m, which grew only to about 150 $\mu$m after 30 minutes (Figure \[fig:ridge\]). The wetting ridge can, however, grow considerably faster for a moving droplet, as we explore more fully in the following section. ### Lubricant Dynamics \[sec:dynamics\] ![image](Figure_3.png) To understand the lubricant dynamics entrained by moving droplets, we tracked the size of the wetting ridge and the thickness of the lubricant in key position with time (Figure \[fig:experiment\]a). The droplet was held in place by a capillary tube, while the SLIPS sample with initial film thickness $h_{i}$ was moved at controlled speeds $U = 75-700$ $\mu$m/s using a linear motor. In all of our experiments, the SLIPS samples consisted of randomly oriented nano-plates of size 10 nm, spaced 200 nm apart on glass substrates [@kim_hierarchical_2013]. The spatial distribution of the lubricant around and under a moving droplet can be observed using Reflection Interference Contrast Microscopy (RICM) (Figure \[fig:experiment\]b) [@de2015air; @daniel_oleoplaning_2017]. Briefly, we shone a monochromatic light of wavelength $\lambda = 532$ nm from beneath a transparent substrate, and in the presence of a thin lubricant film, light reflected off the two film interfaces will interfere either constructively or destructively to form bright or dark fringes, respectively. Between two bright/dark fringes, there is a difference in film thickness of $\lambda/2n_{\text{lub}}$, where $n_{\text{lub}}$ is the refractive index of the lubricant film. The uniformly dark region around the droplet corresponds to the wetting ridge, as light that reflects off the angled ridge is not collected by the objective (Supplementary Section S4). The external radius of the wetting ridge $r_{\text{ext}}$, either at the advancing or receding front, was also monitored optically from the side using a high-resolution camera fitted with a microscope objective or a telecentric lens. At the same time, the thicknesses of the initial lubricant film $h_{i}$, at the trail behind the moving droplet $h_f$, under the droplet $h_d$, and wrapping around the droplet $h_w$ were measured using white-light interferometry. White-light reflected off the thin film is collected by an optical fiber of spot size $\sim 50 ~\mu$m and analyzed using a spectrometer. Thicknesses in the range between hundreds of nanometers to tens of microns can be determined this way; details of set-up have been reported in our previous work [@daniel_oleoplaning_2017]. In our experiment, $h_{f}$, $h_{d}$, and $h_{i}$ were measured along the midline of the droplet profile, where the lubricant profile is nearly flat with $\Delta h$ of at most $\lambda/4n_{\text{lub}} \sim$ 100 nm. Experimentally, we found that both $r_{\text{ext}}$ and $h_{f}$ grew (initially) with the distance travelled by the droplet (Figure \[fig:experiment\]c) as the lubricant was being depleted. We can understand the scaling of $h_{f}$ and $r_{\text{ext}}$, since this behavior is analogous to the classical Landau-Levich-Derjaguin (LLD) problem [@derjaguin1943; @Landau1942; @daniel_oleoplaning_2017; @keiser2017drop]. There is a pressure difference between the wetting ridge and the trailing lubricant film behind the droplet that must be balanced by viscous dissipation in the transition region of size $d_f$ (bounded in red in Figure \[fig:scaling\]a). The film thickness $h_{f}$ can be deduced by balancing $\nabla P$ and $\eta \nabla^{2} U$ in this region, i.e. $(\gamma_{lv}/d_f)(1/r_{\text{ext}}-1/R) \sim \eta U/h_{f}^{2}$, and matching the curvature in this transition region $\partial^2 h_f/\partial^2 x \sim h_f/d_f^2$ with that of wetting ridge $1/r_{\text{ext}}$, i.e. $d_{f} \sim \sqrt{l \;h_{f}}$. Combining these relations gives us the following scaling: $$\label{eq:hfScaling} h_f/r_{\text{ext}} \; (1-r_\text{ext}/R)^{2/3}\sim Ca_{lv}^{2/3},$$ where $Ca_{lv}=\eta U/\gamma_{lv}$ is the corresponding capillary number. When $r_{\text{ext}} \ll R$, we recover the classical LLD results where $h_f/r_{\text{ext}} \sim Ca_{lv}^{2/3}$, i.e. $h_f/r_{\text{ext}}$ does not change with distance travelled (Figure \[fig:scaling\]b). For large droplets ($V = 25$ $\mu$l, $R = 2.05$ mm), the LLD classical law is well-obeyed over a wide range of capillary numbers $Ca_{lv}$ = $10^{-5}-10^{-3}$ with perfluorinated and silicone oils used as lubricants. The red line in Figure \[fig:scaling\]c shows the best-fit line, with a pre-factor of $\beta = 1.44$, in good agreement with the numerical value obtained in the classical Landau-Levich analysis, $\beta = 0.643(3)^{2/3} \approx 1.34$ [@probstein2005physicochemical]. The data in Figure \[fig:scaling\]c was taken using $h_i = 4$ $\mu$m and a constant drop volume of $25$ $\mu$l across experiments, but for a range of tested lubricant thicknesses, we found no direct dependence of $h_f/r_{\text{ext}}$ on initial thickness. For droplets smaller than $V < 10 \mu$l, the effect of $R$ can no longer be ignored and Equation \[eq:hfScaling\] applies. Details on the scaling behavior observed for different initial conditions and droplet radii can be found in the Supplementary Figures S3 and S4. ![image](Figure_4.png) ![image](Figure_5.png) We can make a similar argument about the scaling of $h_d$, the thickness under the droplet, but in this case, the transition region is between the advancing wetting ridge and under the droplet, as shown in Figure \[fig:scaling\]d. Thus, the pressure difference is $\Delta P = P_{\text{ridge}}-P_{\text{drop}} = -\gamma_{ld}(1/r_{\text{int}}+1/R)$. Using the same arguments we used when deriving Equation \[eq:hfScaling\], we arrive at the following result: $$\label{eq:hdScaling} h_d/r_{\text{int}} \; (1+r_{\text{int}}/R)^{2/3} \sim Ca_{ld}^{2/3},$$ where the capillary number here is defined using the interfacial tension between the droplet and the lubricant, i.e. $Ca_{ld}=\eta U/\gamma_{ld}$. As $r_{\text{int}}$ is difficult to measure directly, we measured the external radius of the advancing wetting ridge $r_{\text{ext}}$ and used the relation established in Equation \[eq:CurveBalance\] to calculate $r_{\text{int}}$. We found that the term $h_d/r_{\text{int}} \; (1+r_{\text{int}}/R)^{2/3}$ is constant throughout the distance travelled in a given experiment (Figure \[fig:scaling\]e). We see that the scaling behavior follows Equation \[eq:hdScaling\], as shown in Figure \[fig:scaling\]f. The pre-factor in this case is 2.58, which differs substantially from that in classical LLD analysis, since we have ignored the three-dimensional nature of the fluid flow at the droplet base [@lhuissier2013levitation]. The deviation between silicone and perfluorinated oils in Figure \[fig:scaling\]f at high capillary numbers is likely due to the difficulty in aligning the optical probe when the droplet is moving at high speeds. Note that Equation \[eq:hdScaling\] is slightly different than the scaling reported by @daniel_oleoplaning_2017, where the effect of the wetting ridge on the droplet geometry was neglected and it was assumed that $h_d/R \sim Ca_{ld}^{2/3}$ [@daniel_oleoplaning_2017]. Importantly, this discrepancy does not change the scaling law for the dissipation force on a moving droplet reported in that paper. We expected a similar framework to apply to the dynamic thickness of the lubricant wrapping layer $h_w$. For a static droplet at equilibrium, $h_w$ is stabilized by Van der Waals’ interactions and is typically tens of nm thick (Supplementary Figure S5). A moving droplet, however, will entrain a lubricant film with it and $h_w$ thickens with increasing velocity. We follow the analysis used for $h_f$ and $h_d$ to determine the scaling behavior. In this case, the pressure difference in the transition region—between the wetting ridge and the lubricant in the wrapping layer—is $\Delta P = P_{\text{ridge}}-P_{\text{wrapping}} =-\gamma_{lv}(1/r_{\text{ext}}+1/R)$, resulting in the equation: $$\label{eq:hWScaling} h_w/r_{\text{ext}} \; (1+r_{\text{ext}}/R)^{2/3} \sim Ca_{lv}^{2/3},$$ which simplifies to $h_w/r_{\text{ext}} \sim Ca_{lv}^{2/3}$ when the wetting ridge is much smaller than the dimensions of the droplet. A strict LLD analysis however no longer holds because of the spherical geometry of the droplet. This gives rise to a complex 3D fluid flow and a resulting wrapping layer that is non-uniform in thickness, which can be visualized using color-interferometric techniques [@WLI]. We illuminated the droplet using diffuse white lighting; the local film thickness can now be deduced from the ensuing interference patterns captured using a DSLR camera (Figure \[fig:Wrap\]a). Droplet motion results in a complex lubricant profile. Notably, the lubricant tends to wrap around the sides, forming an extended skirt above the wetting ridge; the lubricant is thicker just above the wetting ridge, but becomes much thinner towards the top of the droplet. Additionally, as compared to the lubricant under and behind a moving droplet, we see much more irregularity in the thickness of the wrapping film, possibly due to the complex interaction between the droplet’s internal flow, the lubricant flow, and the draft in ambient air (Supplementary Figure S5 and Movie S2). This technique can be used to quantitatively describe the profile of a thin film, since each color corresponds to a specific film thickness [@WLI]; it is difficult, however, to distinguish between thicknesses above 500 nm because of the overlap in the color scale (see, for example, the reference colors in Figure \[fig:Wrap\]a). Hence, to check the validity of equation \[eq:hWScaling\], we chose to utilize white-light interference measurements using a spectrometer, as before. The size of the optical probe prevented us from placing it behind the droplet, where the assumptions of LLD are more valid. Hence, we positioned the probe at the side of the droplet, where it is flattest (marked yellow on Figure \[fig:Wrap\]b). Note that because of the poor refractive index contrast and higher variability in thickness, the minimum $h_w$ that can be accurately measured in this configuration is $\sim 400$ nm, which prevents us from measuring thickness early in an experiment or at lower capillary numbers. Because of the complications described above, we do not expect full agreement with LLD results. Experimentally, we find that $h_w/r_{\text{ext}}$ is relatively constant for a given experiment, although there is increased noise due to the variability in $h_w$ (Figure \[fig:Wrap\]c), and scales with $Ca^{2/3}$ (Figure \[fig:Wrap\]d). Not surprisingly, however, the experimentally determined pre-factor $\beta$ = 0.42 differs significantly from the classical result of $\beta \approx 1.34$, which was developed for two-dimensional flow. Additionally, we find that there is more noise at high capillary numbers due to more rapid fluctuations in $h_w$ and more challenging probe alignment. A full description of lubricant dynamics in the wrapping layer is a rich and challenging problem, and is outside the scope of this study. It has been suggested that the presence of the wrapping layer is the major contribution to lubricant depletion [@smith2013droplet]. In our experiments, the maximum value of $h_w$ measured at the highest capillary number was approximately 1.5 $\mu$m. Applying this value to the total droplet’s surface—which would greatly overestimate the amount of lubricant in the wrapping layer—results in a total volume that is about an order of magnitude smaller than the volume of lubricant in the wetting ridge (tens of nl as opposed to hundreds). The wrapping layer is therefore a minor consideration in the overall depletion of the lubricant overlayer; a much more important source of lubricant depletion is the growth of the wetting ridge, which we will discuss in the next section. ![image](Figure_6.png) ### Lubricant Depletion \[sec:Depletion\] In Section II.2, we have described how the various lubricant dynamics and the resultant film thicknesses ($h_{f}$, $h_{d}$, and $h_{w}$) can be understood in terms of the classical LLD problem. Here, we will explain how lubricant depletion arises from the interconnected lubricant dynamics and how it is intimately linked to the growth of the wetting ridge. In particular, we will explicitly show that the volume of the wetting ridge $V_{\text{ridge}}$ is equal to the volume of lubricant being depleted $V_{\text{lost}}$ due to the change in thicknesses $\Delta h = h_{i}-h_{f}$. With this physical insight, we are then able to describe the process of lubricant depletion in SLIPS fully. First, we note that $$\label{eq:V_ridge} V_{\text{ridge}} = \alpha 2\pi a r_{\text{ext}}^2$$ where $\alpha$ is a geometric factor to account for the exact shape. The exact value of $\alpha$ can change as the wetting ridge grows in size and can depend on $Ca$; nevertheless, $\alpha$ should remain at about 0.5, since the wetting ridge can be approximated in the first instance as a triangle. To calculate $V_{\text{lost}}$, we need to know the profile of lubricant trail behind a moving droplet, which we deduced using RICM (Figure \[fig:depletion\]a). Along the midline, we have shown how $h_{f}$ follows the LLD scaling law (Equation \[eq:hfScaling\]). Away from the midline along $y$, we found that the thickness of the lubricant film $h_{f}(y)$ can be described by a modified LLD scaling law $h_f/r_{\text{ext}} \sim (\eta U_{\phi}/\gamma_{lv})^{2/3}$, where $U_{\phi} = U \cos \phi$ is the radial component of the velocity. Equivalently, $h_f(y)/h_{f,0} = (\cos \phi)^{2/3}$, where $h_{f,0}$ is the film thickness at $y=0$ as described by Equation \[eq:hfScaling\]. Although single wavelength RICM can only give information on the relative lubricant thicknesses at different regions, combining RICM with white-light interferometry measurements allows us to deduce the thickness profile $h_{f}(y)$ unambiguously. For lubricants of different viscosities $\eta$ = 10–50 cP, we found a maximum lubricant thickness at $y=0$, which then decreases monotonically towards the edges of the droplet following the modified LLD scaling law described above (dashed line in Figure \[fig:depletion\]b). From the profile, we can integrate numerically to calculate the average thickness behind the droplet, resulting in $<h_{f}> \approx 0.85 h_{f,0} = 0.85 \beta r_{\text{ext}} Ca_{lv}^{2/3}$. Once $r_{\text{ext}}(L)$ and $h_{f,0}(L)$ (and hence $<h_{f}(L)>$) are determined experimentally, the amount of lubricant loss $V_{\text{lost}}(L)$ can then be calculated numerically: $$\label{eq:v_lost} V_{\text{lost}}(L) = \int_{0}^{L} 2(a + w r_{\text{ext}}) \Delta h \, dL + V_{o},$$ where $L$ is the distance traveled by the droplet, $\Delta h = h_i-<h_{f}>$, $w$ is a geometric factor to account for the added width of the wetting ridge, and $V_{0} = \alpha 2\pi a r_{\text{ext,0}}^{2}$ is volume of the wetting ridge of size $r_{\text{ext,0}}$ created when the droplet was first placed on the surface. Figure \[fig:depletion\]c shows the progression of $V_{\text{lost}}(L)$ for droplets moving with different $Ca_{lv}$ and the same $h_{i}$ = 4 $\mu$m. We note that droplets with higher capillary numbers deplete much less lubricant than slower moving droplets on less viscous lubricants, and $V_{\text{lost}}$ appears to plateau to a maximum value for the highest $Ca_{lv} = 1.7 \times 10^ {-3}$—an observation which we will explain later. We also found that the growth of the wetting ridge $V_{\text{ridge}}(L)$ is directly proportional to $V_{\text{lost}}(L)$, as shown in Figure \[fig:depletion\]d. The only fitting parameter here is $\alpha_{\text{fit}}=0.52$, close to the expected value in our analysis (Equation \[eq:V\_ridge\]). We can also directly predict the lubricant loss $V_{\text{lost}}(L)$ by first solving for $r_{\text{ext}}(L)$, which follows the differential equation $\alpha 4\pi a r_{\text{ext}} (dr_{\text{ext}}/dL) = dV_{lost}/dL = 2(a + w r_{\text{ext}}) \Delta h \approx 2a \Delta h$. Replacing $\Delta h$ with the appropriate scaling law, as discussed earlier, this can be integrated and rearranged to give: $$\label{eq:L_integral} \ln\bigg(1-\frac{r_\text{ext}}{r_\infty}\bigg) + \frac{r_\text{ext}}{r_\infty} = -\mu_{1} Ca_{lv}^{4/3} \bigg(\frac{L-\delta}{h_i}\bigg),$$ where $\mu_{1} = \chi^{2} \beta^{2}/(2 \pi \alpha) \approx 0.5$, $\chi = <h_{f}>/h_{f,0} \approx 0.85$, and $r_\infty = h_i/\chi \beta Ca_{lv}^{2/3}$ is the limiting size of the wetting ridge for a given set of experimental conditions. The integration constant $\delta$ is a small positional offset to account for the experimental error in $L$ and the initial wetting ridge size $r_{\text{ext,0}}$. Figure \[fig:depletion\]e shows the growth of $r_{\text{ext}}(L)$ for droplets moving at 0.7 mm/s on surfaces with different initial lubricant thicknesses $h_{i}$ = 1.5–4 $\mu$m of 50 cP silicone oil. As predicted by Equation \[eq:L\_integral\], the data collapses to a single curve on a non-dimensional plot of $r_\text{ext}/r_\infty$ against $Ca_{lv}^{4/3} (L-\delta)/h_i$. The dashed lines are the corresponding best-fit curves with $\alpha$, $\delta$, and $\chi$ as fitting parameters. The fitted values are consistent with our previous analysis: $\alpha_\text{fit} = 0.51 \pm 0.05$; $\|\delta_\text{fit}\|$ is $< 1$ mm, much smaller than the total length travelled $L > 6$ cm, indicating that the error in $L$ and $r_\text{ext,0}$ is minimal; and $\chi_\text{fit} = 0.80 \pm 0.01$, close to the expected value of 0.85. The slight discrepancy in the fitted value of $\chi$ could be due to the finite size of the wetting ridge, which we have ignored when deriving equation \[eq:L\_integral\]. Details on the numerical fit can be found in Supplementary Section S8 and Table S3. An analytic solution also exists in the limit that $r_\text{ext}/r_\infty \ll 1$, whereby $\ln(1-r_\text{ext}/r_\infty) + r_\text{ext}/r_\infty \approx -1/2(r/r_\infty)^{2}$, and equation \[eq:L\_integral\] simplifies to $$\label{eq:small_r} \begin{split} r_\text{ext} &= \sqrt{\frac{h_i(L-\delta)}{\pi \alpha}}, \end{split}$$ i.e. the growth of the wetting ridge is initially independent of the droplet’s speed and fresh drops cause significant local depletion regardless of capillary number. Equation \[eq:small\_r\] can be also be derived by noting that in this limit, $\Delta h \approx h_i$ and hence $dV_{lost}/dL \approx 2a h_i$. Once $r_{\text{ext}}(L)$ is known, $h_{f,0}(L)$ can be found trivially by applying LLD law (dashed lines in Figure \[fig:depletion\]f, where $h_\infty = \beta r_\infty Ca_{lv}^{2/3}$) and $V_{\text{lost}}(L)$ then follows from Equation \[eq:v\_lost\]. Note that as $r_{\text{ext}}$ increases, the Laplace pressure decreases, and the rate of lubricant depletion decreases until it reaches zero when $\Delta h$ = 0 and hence $dV_{\text{lost}}/dL = 0$; this occurs when $h_{f,0} = h_\infty$ and $r_{\text{ext}} = r_\infty$. The maximum amount of lubricant loss can then be deduced by noting that $V_\text{lost,max} = V_{\text{ridge,max}}$, i.e. $$\label{eq:V_lost_max} V_{\text{lost,max}} = \alpha 2\pi a r_\infty^{2} = \frac{a \; h_i^2}{\mu_{1}Ca_{lv}^{4/3}}.$$ While we have only explicitly demonstrated lubricant depletion due to water droplet, the results presented here, such as Equation \[eq:V\_lost\_max\], can be applied to other liquid droplets (including for small $\theta_{\text{app}}$) as long as $r_{\text{ext}} << R$. This framework leads us to several conclusions, some of which run against intuitive expectations. Equation \[eq:V\_lost\_max\] shows that droplets moving at higher velocities and capillary numbers will cause less lubricant to be lost. From previous work, we know that the drag force for a droplet moving across SLIPS scales with $F_d \sim \gamma R Ca^{2/3}$ [@daniel_oleoplaning_2017; @keiser2017drop]. Counter-intuitively, this means that droplets moving across the surface with a higher driving force and correspondingly higher shear rate deplete less lubricant than slower-moving droplets. We can further consider how the size of the droplet affects lubricant loss. We note that $V_{\text{lost}}$ scales with $a \sim R$, while droplet volume scales with $R^3$. Thus, to minimize depletion, it is advantageous to have one large droplet rather than several smaller droplets of the same total volume. For applications such as condensation where water initially forms on the surface as small, discrete droplets, strategies that promote rapid coalescence into bigger droplets can lead to improved longevity [@park2016condensation]. In our paper, we have made extensive use of LLD analysis, which is known to break down for large $Ca > 10^{-2}$ [@spiers_free_1974; @bretherton_motion_1961; @white_theory_1965; @maleki_landaulevich_2011]. However, we can expect the lubricant thickness to scale as $h \sim r Ca^{\nu}$, where $\nu$ is some exponent which differs from 2/3 [@snoeijer2006avoided; @maleki_landaulevich_2011; @snoeijer2013moving]; in which case, many of the results discussed here can still be applied with some modifications. For example, the amount of lubricant loss can be generalized to $V_{\text{lost,max}} = a \; h_i^2/\mu_{1}Ca_{lv}^{2 \nu}$ (equation \[eq:V\_lost\_max\]). Our preliminary results indicate that $\nu \approx 1/4$ for $Ca > 10^{-2}$; its exact value (and its derivation) is still an open question and beyond the scope of this study (Supplementary Figure S6). The amount of lubricant lost scales with $h_i^2$. As lubricant is depleted, less and less volume will be lost, with little impact on surface performance since, as we showed in earlier work, $F_{d}$ is independent of $h_i$ [@daniel_oleoplaning_2017]. This will remain true until the lubricant thickness becomes nano-metric in size, when dispersion forces (such as van der Waals’ interactions) will have to be considered. This will be a natural extension to this work in the future. Finally, we have only used nano-structured surfaces, where the lengthscale of the structures is significantly smaller than the micron-scale lubricant thicknesses. The scaling relationships derived in this work will also apply directly to flat surfaces, such as liquid-infused organogels [@urata2015self; @cui2015dynamic], but will have to be modified for microstructured surfaces. However, the main idea outlined in this work—that the wetting ridge is a low-pressure region and its growth drives lubricant depletion—is general and likely to remain true for most surfaces. Conclusions =========== Our work here can be split into three parts. In part I, we show that the geometry of a droplet on SLIPS can be understood by balancing Laplace pressure and using geometric arguments. In part II, we showed how the various lubricant thicknesses change dynamically with speed and can be deduced—analogous to the classical Landau-Levich-Derjaguin problem—by balancing the pressure gradient and viscous stress at the edge of the wetting ridge. Finally, in part III, we use this understanding to identify the growth of the wetting ridge as the main source of lubricant depletion and to quantify the amount of lubricant that a moving droplet collects as it sweeps across a lubricant-infused surface. While we have only explicitly discussed lubricant depletion due to water droplet motion, many of the ideas explored here will be useful in understanding lubricant depletion by other droplets and in very different situations, such as during ice formation and droplet condensation on lubricated surfaces. By identifying the main source and mechanics of lubricant loss on SLIPS, our work will inform the design of longer-lasting lubricant-infused surfaces. Materials and Methods \[sec:mat\] ================================= Boehmite Synthesis. All SLIPS used in this work were created using transparent thin film of nanostructured boehmite on glass [@kim_hierarchical_2013]. Briefly, an alumina sol-gel solution was spin-coated onto 3x1" glass microscope slides at 1000 rpm and dried at 70 C for 1 h. Boehmite was formed from the alumina sol gel by submersion in DI water for 30 min at 60 C. The surfaces were rinsed with DI water and then blown dry with nitrogen. Surface Functionalization. For SLIPS infused with a silicone oil as a lubricant, the nanostructured sample was placed in a sealed jar with a small piece of cured Sylgard 184 10:1 PDMS and heated at 235 C for 7 h [@PDMSfunc]. Samples were then rinsed with ethanol and dried with nitrogen before application of silicone oil. SLIPS samples infused with perfluorinated polyether oils were first functionalized using perfluoroalkyl phosphate ester (FS100 Surfactant). Boehmite-coated glass slides were submerged in a solution of 95:5:1 by weight ethanol:DI Water:FS100 for 1 h at 70 C. Samples were then rinsed thoroughly with acetone, ethanol, and IPA and blown dry using nitrogen before application of perfluoropolyether oils. Lubricant Application. Silicone oils, purchased from Sigma Aldrich, with viscosities in the range of 5 to 50 cP were used. The interfacial tensions (IFTs), as measured using the pendant droplet method, were roughly 19 mN/m in air and 42 mN/m in water, with minor variations due to viscosity. Two perfluoropolyethers were used with viscosities of 23.2 cP and 72.6 cP (Dupont Krytox GPL 100 and 102, respectively). The IFT of the Krytox oils was 16 mN/m in air and 58 mN/m in water, again with minor variation with viscosity. Lubricants were applied by spin-coating at defined speeds and the film thickness was measured using white light interferometry. Dyed water. Black, dyed water was used in order to minimize optical reflections during measurements. A thick layer of soot was created on a clean glass petri dish by placing it over a candle-flame. The soot was hydrophilized by exposure to oxygen plasma for 5 min, dissolved in pure de-ionized millipore water, and filtered through a 0.45 $\mu$m cellulose filter. The resulting solution was used as a stock solution that was then diluted 5:1 for all measurements and experiments. The IFT of the dyed droplet in air and with oil was measured using the pendant drop method and found to differ from that of pure water by less than 1%. Wetting ridge measurement. A digital camera (Panasonic GH4) was calibrated for scale and used to take pictures of the wetting ridge profile at a rate of 1 frame per second. The point at which the wetting ridge met the horizontal surface and the point where the wetting ridge met the droplet were tracked in 2D space using an open-source tracking software [@tracker]. The wetting ridge radius was calculated as the average of the difference in the $x$ and $y$ coordinates of these two points. In cases where the wetting ridge was discontinuous with the surface of the droplet, the radius was calculated as $(\Delta x^2+\Delta y^2)/2 \Delta y$, where $\Delta x$ and $\Delta y$ are the difference in the $x$ and $y$ coordinates of the two points. Dynamic Thickness Measurements. Thickness measurements were performed using an Ocean Optics USB2000+ spectrometer with a halogen lamp as the white-light source. A reflectance-mode optical fiber was placed under the sample and immersion oil was placed between the glass and the probe to eliminate reflection from the back of the glass slide. The spectrum was normalized against the light source, resulting in a series of peaks and valleys appearing due to the difference in path-length between the lubricant-substrate and lubricant-air/water interfaces. By analyzing the wavelengths of the interference maxima and minima, the thickness of the thin films could be unambiguously determined in a range from 400 nm to several microns, as described previously [@daniel_oleoplaning_2017]. Reflection Interference Contrast Microscopy. Samples were imaged with a custom inverted microscope in reflection mode. Monochromatic light was produced by passing broadband LED illumination through a 532 nm filter. Thus, two adjacent maxima or minima differ in thickness by $\lambda/2n_{\text{lub}}$ or 0, and assumptions about the shape/initial thickness must be made in order to obtain a quantitative thickness profile. Fluorescence Confocal Imaging. Confocal imaging was done using a Zeiss LSM 700 upright confocal with a 40X water immersion objective. 20 cP silicone oil was dyed with 2.5% by volume of DFSB-K175 fluorescent dye to generate a fluorescence signal. Further details can be found in Supplementary Section S2. The work was supported partially by the ONR MURI Award No. N00014-12-1-0875 and by the Advanced Research Projects Agency-Energy (ARPA-E), U.S. Department of Energy, under Award Number DE-AR0000326. J.V.I.T. was supported by the European Commission through the Seventh Framework Programme (FP7) project DynaSLIPS (project number 626954). We acknowledge the use of the facilities at the Harvard Center for Nanoscale Systems supported by the NSF under Award No. ECS-0335765. M.J.K thanks the Natural Sciences and Engineering Research Council of Canada (NSERC) for a PGS-D scholarship. 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import { Injectable } from '@angular/core'; import { BehaviorSubject } from 'rxjs/BehaviorSubject'; import { DoubleButtonActive } from '../components/layout/double-button/double-button.component'; @Injectable() export class NavBarService { switchVisible = false; activeComponent = new BehaviorSubject(1); leftText: string; rightText: string; switchDiabled = false; setActiveComponent(value) { this.activeComponent.next(value); } showSwitch(leftText, rightText, selectedButton = DoubleButtonActive.LeftButton) { this.setActiveComponent(selectedButton); this.switchDiabled = false; this.switchVisible = true; this.leftText = leftText; this.rightText = rightText; } hideSwitch() { this.switchVisible = false; } enableSwitch() { this.switchDiabled = false; } disableSwitch() { this.switchDiabled = true; } }
Functional characterization and expression analysis of the proteinase-activated receptor-2 in human cutaneous mast cells. Proteinase-activated receptor-2 (PAR2) belongs to a new G protein-coupled receptor subfamily activated by serine proteinases. PAR2 has been demonstrated to play a role during inflammation and immune response in different tissues including the skin. We examined whether PAR2 is functionally expressed by cutaneous human primary skin mast cells (HPMC) and the human mast cell line 1 (HMC-1). Reverse transcription-polymerase chain reaction and FACS analysis show expression of PAR2 both at the RNA and protein level. HPMCs and HMC-1 also express PAR1, PAR3, and PAR4. Ca-mobilization studies demonstrate functional PAR2 expressed by human skin mast cells, as shown by natural and synthetic PAR2 agonists. PAR2 agonists induced histamine release from HPMC indicating a role of PAR2 in regulating inflammatory and immune responses by skin mast cells. Double-immunofluorescence staining reveals colocalization of PAR2 with tryptase in the majority of human skin mast cells. In conclusion, trypsin and tryptase as well as specific agonists for PAR2 were able to induce Ca2+ mobilization in HPMCs, and agonists of PAR2 induce the release of histamine from these cells. Thus, PAR2 may be an important regulator of skin mast cell function during cutaneous inflammation and hypersensitivity.
Dominae, Philosophy of (A to Z Challenge, D) 4 April, 2015 The draconic philosophy of Dominae is based on achievement through personal power and will alone. “A dragon flies alone needing nothing beyond themself, but accept that others will wish to serve you and that is your right.” It was founded and popularized by the Empress herself and it is the foundation of the Imperium. The Cardinal Beliefs of Dominae are: Acquisition, a dragon is expected to acquire power, physical wealth and knowledge, roughly in that order. The strong take from the weak, that is the natural order of things, and no one is stronger then a dragon. Some view the acquisition of property and people as the most important aspect, while other dragons seek only to own what they can carry with them. In any case, no dragon will forgive those who steal from them. Ambition, there is always more to achieve and more to obtain, it is not the place of a dragon to be content with what they have. There is a world out there, make it yours. Consumption, the strength of the physical form must be maintained. Naturally, only the best food will do, preferably hunted by the dragon itself. Some dragons insist upon eating only intelligent prey or only prey that can fight back, others seek out the most exotic foods. Leisure, among the perks of power, is the time to devote to relaxation. A dragon thus proves his power by not having to constantly prove his strength and power. Such times are often turned to strange pursuits such as collecting or various artistic endeavors for those who cannot bear to simply do nothing. Possession, that which is yours is yours to do what you wish with. No other being has the right to tell you how to treat your goods. You may squander, change or destroy your possessions as you choose, their destiny is what you allow, nothing more. Privilege, you embody the highest power in the world and the skies above, nothing else is your equal. You look down on others as they are provably inferior to you. Retaliation, no one opposes you without risk or consequence, enemies are crushed, rivals are destroyed and barriers are swept away. Those that would challenge you will know your power and anger when you meet. Though the Empress does not encourage such, there are cults that have sprung up that treat Dominae as their central dogma, some of these worship the Empress directly, others dragons more generally. Oddly, since the Imperium was founded, the Empress has stopped keeping slaves. However, no one questions her devotion to her philosophy. A Cleric of the Dominae can choose from the Destruction, Magic, Strength and War domains.
Introduction {#s1} ============ Mucosal homeostasis at the gastrointestinal tract requires a delicate co-existence of gut microbiota with the gut-associated mucosal immune system, an interaction that is constantly challenged by environmental factors. Hence, mucosal "health" is depended on an intact genetic structure, preserved by the integrity of the epithelial barrier, and fine-tuned by immunoregulatory responses. Failure of one or more of these balancing elements leads to breakdown of homeostasis and predominance of pro-inflammatory immunological circuits. The latter are critically dependent on key cellular and/or soluble mediators, most prominent among which are cytokines and their receptors. The prototypical disorders that are signified by such dysregulated mucosal immunity are the Inflammatory Bowel Diseases (IBD), in particular Crohn\'s disease (CD) and ulcerative colitis (UC). Thus, it is of no surprise that cytokines have been the main targets of therapeutic interventions in IBD, which represents a rapidly expanding field in recent years. TL1A (Tumor necrosis factor-like cytokine 1A) was first reported in 2002 ([@B1]). It is a member of the TNF superfamily of proteins (TNFSF) and it is encoded by the Tnfsf15 gene that is located on chromosome 9q32 in humans and chromosome 4 in mice. TL1A is a type II transmembrane protein with a molecular weight of 28 kDa, which contains 251 amino acids. Similar to other members of the TNF-family, TL1A forms a stable trimer. It exists in a membrane-bound form (mTL1A), which may also be cleaved by matrix metalloproteinases and released as soluble, fully-functional 20-kDa protein (sTL1A) ([@B1], [@B2]). The functional receptor for TL1A is DR3 (death domain receptor 3), which is encoded by the Tnfrsf25 gene that is located at the 1p36.3 position in humans ([@B3], [@B4]). DR3 is a type I membrane protein with a 417 AA sequence and a molecular weight of 45 kDa that shares the highest homology to TNFR1 among all members of the TNFRSF. DR3 contains a death domain in its cytoplasmic region; thus it may participate in apoptotic processes. Nevertheless, DR3 signaling also mediates inflammatory/immunological responses. An important characteristic of human DR3 is the existence of several splice variants (13 in humans and 10 in mice). The functional implications of such variety are not fully understood, although encoded proteins may differ in their function ([@B5]). To date, the only proven ligand for DR3 is TL1A (including the short variant, TL1/vascular endothelial growth inhibitor). There is now able evidence that interactions between TL1A and its functional receptor DR3 affect gut mucosal immunity both during homeostatic conditions and in various inflammatory states ([Figure 1](#F1){ref-type="fig"}). In particular, their role in IBD is supported by a variety of genetic, immunological, experimental, and translational data. The current review aims to critically present existing literature on the role of TL1A and DR3 in mucosal immunity. ![The TL1A/DR3 system as a central regulator of mucosal immune responses, allergy and autoimmunity. TL1A is not constitutively expressed but is induced in mucosal APCs (and other types of immunocytes) following stimulation via microbial and non-microbial antigens. TL1A binds to the functional receptor, DR3, which is expressed by various lymphocytic populations upon activation. TL1A/DR3 signaling enhances proliferation and optimizes cytokine production by responding lymphocytes, acting as a co-stimulatory system that amplifies TCR or cytokine provided signals. This function is of particular importance under conditions of sub-optimal lymphocyte stimulation. All types of effector T cells (Teff: Th1, Th2, Th9, Th17) respond to stimulation with TL1A. DR3 is also expressed by regulatory lymphocytes (Tregs), which proliferate in response to TL1A, although this may be accompanied by a temporary halt of suppressive function, especially in the event of acute inflammation. DR3 expression has also been demonstrated in innate lymphoid cells (ILCs) and DR3 signaling affects their function. Finally, TL1A/DR3 signaling pathways have been reported in NK and NK-T cells, as well as CD8+ lymphocytes. This universal expression of DR3 by innate and adaptive effector and regulatory populations implies a key regulatory role of the TL1A/DR3 system in mucosal immunity. Alongside, experimental data from animal models and translational data from patients indicate an important contribution of the TL1A/DR3 system in allergic lung inflammation and autoimmune diseases such as Crohn\'s disease, Ulcerative colitis, Rheumatoid arthritis, and Psoriasis.](fimmu-10-00583-g0001){#F1} Tnfsf15 Polymorphisms Affect Susceptibility to Intestinal Diseases {#s2} ==================================================================== A first line of evidence for the potential importance of TL1A in the pathogenesis of IBD is derived from studies that reported significant associations between genetic variations in the Tnfsf15 gene and susceptibility to IBD ([Table 1](#T1){ref-type="table"}). ###### Genetic associations of Tnfsf15 gene with susceptibility and phenotype of IBD. --------------------------------------------------------------------------------------- Polymorphism Ethnicity Susceptibility/Phenotype References ------------------ ------------------- ------------------------------ ----------------- rs3810936 Asian, Caucasian\ CD\ ([@B6]) Asian UC rs6478108 Asian, Caucasian\ CD\ ([@B6])\ \ \ ([@B7])\ Asian, Caucasian\ UC\ ([@B8])\ Asian CD B2/B3 ([@B9]) rs4979462 Asian CD ([@B6]) rs6478109 Asian, Caucasian\ CD\ ([@B6])\ \ \ ([@B7])\ \ \ ([@B10])\ Asian UC ([@B6]) rs7848647 Asian, Caucasian\ CD\ ([@B6])\ Asian\ UC\ \ Caucasian, Asian CD early onset ([@B7], [@B11]) rs7869487 Asian, Caucasian CD ([@B6]) rs4263839 Caucasian\ Colonic CD location\ ([@B12])\ Caucasian\ Bowel resection\ ([@B13])\ Asian CD, B2/B3 ([@B14]) rs4574921 Asian CD B3p ([@B9]) rs11554257 Caucasian MR-UC ([@B15]) rs3810936 Asian\ Severe CD\ ([@B16])\ Asian\ CD\ ([@B17])\ Asian CD B3p ([@B7]) rs4246905 Asian IBD ([@B18]) --------------------------------------------------------------------------------------- MR, Medically refractory; B2, B3, p, Montreal classification indicators for Crohn\'s disease. In 2005, Yamazaki et al. were the first to report that a specific genetic variant of Tnfsf15, tnfsf15_28, was strongly associated with susceptibility to IBD in Japanese patients, whereas the gene was monomorphic in a Caucasian population from the UK ([@B19]). Further investigation of these two ethnic groups revealed 5 different SNPs, tnfsf15_26, 31, 35, 36, and 41, that were polymorphic in both groups, forming three different haplotypes which affected susceptibility to IBD. In both ethnic groups, haplotype A was identified as a high-risk marker for susceptibility to IBD, whereas haplotype B was found to be a low-risk genetic factor. Haplotype C was not significantly associated with IBD risk in either population, despite its frequent detection. Two years later, Picornell et al. investigated the aforementioned three haplotypes in Jewish and non-Jewish IBD and control populations in Los Angeles, USA. In the non-Jewish population, similar to the previous study, haplotype B was less frequent in both CD and UC patients compared to controls, highlighting a possible protective role ([@B20]). On the other hand, no association of haplotype A with IBD was seen in either population, suggesting that Tnfsf15 polymorphisms are ethnic-specific. These findings were further supported by independent studies from Asia and Europe. Interestingly, haplotype B of the Tnfsf15 gene has been found to affect protein production by monocytes and macrophages. Peripheral CD14+ monocytes and monocyte-derived macrophages from patients carrying Haplotype B or the rs6478109 A minor allele produce higher levels of TL1A in response to FcγR or LPS stimulation ([@B21], [@B22]). Interestingly, haplotype B has been reported to confer CD risk in Jewish patients but the rs6478109 A minor allele conferred protection to subjects of European descent. However, the studies on the effect of TL1A gene Haplotypes on membrane bound TL1A has provided conflicting results. Earlier studies have shown that membrane expression of TL1A was up-regulated on peripheral monocytes from Jewish but not from non-Jewish CD patients that carry the B haplotype but later studies have shown increase membrane bound TL1A in homozygotes of the protective rs6478109 A allele in European descent subject ([@B21], [@B22]). A Korean study in pediatric CD patients and adult controls showed that six specific haplotypes of the Tnfsf15 gene were more frequently reported and, of those, two were significantly different between the two groups; the haplotype including T-C-A-T-C SNPs (rs3810936-rs6478108-rs6478109-rs7848647-rs7865494) was more frequent in controls, whereas haplotype including C-T-G-C-C SNPs in CD patients ([@B7]). On the other hand, in a Chinese study consisting of 13 pediatric patients with Very-early-onset IBD (VEO-IBD), no association between Tnfsf15 gene mutations and VEO-IBD was found and this finding may be the result of either ethnic differences or the small number of patients included in the study ([@B23]). Contrary to the previous study, it was recently shown that the Tnfsf15 rs4246905 SNP was associated with development of CD in children with chronic granulomatous disease ([@B24]). The importance of the ethnic background for Tnfsf15 polymorphisms was further highlighted in an Indian study showing that haplotype A was significantly more frequent in IBD cases than in healthy individuals, while the opposite was observed for haplotype C. Further investigation identified two additional SNPs (rs10114470 and rs4263839) and generated 7 different haplotypes, from which haplotype H had a possible protective role being more frequent in healthy individuals, whereas haplotypes I and J conferred susceptibility to IBD ([@B25]). Haplotypes of the Tnfsf15 gene that are associated with either susceptibility or protection from CD have also been reported in the European population ([@B26]). Similar to Yamazaki, a Korean study showed that the allele T of the SNP rs6478108 is indeed a "risk" allele as it is more frequently found in patients with UC ([@B8]). In a recent study that included a large number of IBD patients and healthy individuals across Europe and Asia showed that, although allele frequencies are similar between the European and Asian population, Tnfsf15 variants have a stronger association with IBD susceptibility in people originating from Asia ([@B18]). Other studies have also proposed that certain Tnfsf15 alleles may bear prognostic value for the severity of IBD. In the Chinese population, the T allele of SNP rs10114470 was associated with increased probability of developing stricturing, penetrating, or perianal complications ([@B27]). In the same notion, Pernat Dobrez et al. identified the SNP rs4263839 as a possible marker for disease progression. In their study, 72.2% of CD patients who were carriers of allele A had progressed from an inflammatory (B1) to stricturing (B2) or penetrating (B3) phenotype, as compared to only 55% of those bearing the allele G ([@B28]). In another study, polymorphisms in the Tnfsf15 gene were associated with medically refractory UC ([@B15]). The susceptibility loci for CD reported by Yamazaki et al. were also detected in CD patients from Ryukyu Islands, near Japan. Interestingly, CD patients, bearing the risk alleles, had increased bacterial abundances of Bacteroidetes and more specifically, of Prevotella, but whether the genetic background is the outcome of microbiome composition alteration or vice versa, remains unclear ([@B29]). Interestingly, besides IBD, Tnfsf15 genetic variants have also been associated with other GI diseases, such as diverticulitis and Irritable Bowel Syndrome (IBS). Connelly et al. discovered that the SNP rs7848647 is highly associated with diverticulitis and that haplotype carriage may predict the need for surgical intervention ([@B30]). Additional protective or risk-conferring haplotypes for diverticulitis were reported later by the same group ([@B31]) Regarding IBS, Zucchelli et al. reported a strong association between the SNP rs4263839 and patients suffering from IBS. In particular, the G allele of the SNP rs4263839 was identified as a high-risk marker and further investigation revealed that it could lead to higher expression levels of TNFSF15 in healthy individuals ([@B32]). Taken together, various SNPs of the Tnfsf15 gene have been associated with not only IBD, but also diverticulitis and IBS, and seem to be promising predictors for intestinal disease susceptibility and/or progression. Nonetheless, the interpretation of the role of Tnfsf15 mutations seem to be influenced by ethnic background, as a stronger association with Asians has been reported. In addition, no definitive functional implications for existing, risk-associated polymorphisms have been reported. Nevertheless, a few studies have proposed that certain polymorphisms may be associated with specific functional effects, a finding that, interestingly, was also affected by the ethnic background in some cases ([@B22], [@B33], [@B34]). The Complex Role of tl1a/dr3 in Mucosal Immunity {#s3} ================================================ Expression, Regulation, and Function of the TL1A/DR3 System in Immune Cells --------------------------------------------------------------------------- ### Mononuclear Phagocytes The cellular sources of TL1A and requirements for its expression indicate its important role in innate and adaptive immune responses especially at the intestinal mucosa. Besides the original description of its constitutive expression in endothelial cells ([@B1]), TL1A was also found to be expressed by mononuclear phagocytes at the intestinal lamina propria of both mice and humans under inflammatory conditions. In particular, early studies in murine models of ileitis and colitis have shown that TL1A was mainly expressed by CD11c^high^/MHC-II^+^ mononuclear phagocytes of the lamina propria and the MLNs and CD11c^low^/MHC-II^−^ mononuclear phagocytes of the lamina propria that probably represent dendritic cells and macrophage subsets ([@B35], [@B36]). In patients with CD or UC immunolocalization of TL1A was reported in tissue macrophages and lymphocytes, as well as in infiltrating plasma cells in UC ([@B37]). A recent study has further characterized lamina propria mononuclear phagocytes that primarily produce TL1A in mice, CD patients and healthy subjects and reported expression of CD14 and CX3CR1 surface markers, which classifies them as antigen sampling mucosal macrophages. TL1A production by CD11c^+^CX3CR1^+^ mononuclear phagocytes correlated with disease activity in CD in humans. In mice CD11c^+^CX3CR1^+^ mononuclear phagocytes produced TL1A, in a MyD88-dependent fashion, in response to mucosal-adherent bacteria ([@B38]). The abundant cellular expression of TL1A in APCs, led to studies on the regulation of its expression in this particular population. These studies showed that TL1A expression by APCs is responsive to signaling through FcRγ receptors, TLRs or microbial antigens. In particular, in monocytes and monocyte-derived dendritic cells (DCs) TL1A mRNA and protein (both soluble and transmembrane forms) was highly induced by FcRγ stimulation through plate-bound, cross-linked human IgG ([@B39]). A potential clinical relevance of this association was implied in two studies in rheumatoid arthritis (RA). Cassatella et al. reported that mononuclear phagocytes strongly expressed TL1A in rheumatoid factor--positive but not rheumatoid factor--negative patients ([@B40]). In vitro stimulation of monocytes with various preparations of insoluble immune complexes led to significant upregulation of TL1A ([@B40]). Furthermore, Bamias et al., demonstrated that soluble TL1A concentrations were significantly higher in rheumatoid factor--positive than rheumatoid factor--negative patients ([@B41]). In addition to stimulation through the FcRγ receptor, bacterial signals also upregulate the expression of TL1A. In the monocytic cell line U937, TL1A was induced by LPS. This pathway involved activation and binding of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) to a specific binding site in the 5′ flanking region of TL1A ([@B42]). LPS responsiveness was also confirmed in bone-marrow derived dendritic cells ([@B43]). Shih et al. studied the effect of stimulation by cultured microorganisms on TL1A expression by monocytes or DCs ([@B44]). Cells were stimulated with a variety of cultured microorganisms (gram-negative \[Escherichia coli, E. coli Nissle 1917, and Salmonella typhimurium\], gram-positive \[Listeria monocytogenes and Staphylococcus epidermidis\], partial anaerobes \[Campylobacter jejuni\], and obligate anaerobes \[Bacteroides thetaiotaomicron, Bifidobacterium breve, and Clostridium A4\]). In all cases, upregulation of TL1A was seen through an NF-kB (as well as p38 MAPK)--dependent mechanism. TLR signaling could only partially substitute for the effect of whole bacteria stimulation. Moreover, TLR7/8 signaling demonstrated a negative effect by significantly decreasing IC-induced TL1A expression of monocytes ([@B45]). In another study, Kamada et al. also reported TL1A induction by heat-killed bacteria in CD-associated LP macrophages ([@B46]). ### Effector Lymphocytes TL1A is also expressed on activated lymphocytes, indicating the formation of positive regulatory loops during mucosal inflammation ([@B47], [@B48]). Especially in the small bowel, membrane bound TL1A is expressed by activated gut specific CCR9^+^ lymphocytes ([@B47]) and it is possibly up-regulated by stimulation through the T-cell receptor (TCR) (i.e., by phytohemagglutinin) ([@B49]). Expression of DR3, the cognate receptor of TL1A, is mainly detected in lymphocytic populations, mostly following activation. DR3 signaling enhances CD4+ lymphocyte proliferation by increasing both IL-2 production and expression of IL-2RA and IL-2RB ([@B1]). The effect of TL1A co-stimulation is particularly important in conditions of sub-optimal stimulation via CD3 or CD28 ([@B43]). TL1A preferentially enhances proliferation of murine memory CD4+ T cells ([@B35]), but can also induce mild proliferation and strong IL-2 and IFN-γ expression by naïve T cells ([@B43]). TL1A co-stimulation of CD4+ T cells results in production of multiple cytokines including IL-2, IL-4, IL-13, interferon-gamma (IFNγ), and IL-17 ([@B1], [@B43], [@B47], [@B48], [@B50]). Although, TL1A-DR3 interaction enhances T cell proliferation and is required for optimal cytokine production, it appears to be dispensable for differentiation of naive T cells into Th1, Th2, or Th17 effector cell subtypes ([@B43]). TL1A-DR3 is proposed as an important system for enhancement of immune responses in the periphery. Indeed, TL1A acts in synergy with IL-12 and IL-18 to enhance adaptive Th1 and innate IFNγ responses by T cells ([@B49], [@B51], [@B52]). Specific T cell subsets that up-regulate IFNγ and TNFα production in response to TL1A and IL-12/18 co-stimulation have been characterized by the expression of CCR9 ([@B47]), CD161 ([@B53]), and IL-18Rα ([@B52]). Interestingly, TL1A responsive T cells were preferentially localized at the intestinal mucosa, which indicates a prominent role of TL1A in intestinal IFNγ-mediated immune responses. Consistent with its role as a non-specific co-stimulator, irrespective of T-cell lineage commitment, TL1A was shown to enhance secretion of Th2 cytokines by activated T cells and amplified IL-13 production by NKT cells in a murine model of allergic lung inflammation ([@B43], [@B48]). The role of TL1A in Th17 responses appears more complex. Pappu et al. found that TL1A^−/−^ dendritic cells exhibited reduced ability to support differentiation of Th17 lymphocytes and TL1A co-stimulation was required for optimal antigen-independent proliferation of differentiated Th17 lymphocytes ([@B50]). In contrast, Jones et al. reported that TL1A-DR3 interactions inhibit polarization toward the Th17 lineage but support IL-17 production in fully committed Th17 cells ([@B54]). Differences of in vitro experimental conditions for Th17 polarization may account for the aforementioned discrepancies. Furthermore, TL1A has been found to induce IL-22 production by human peripheral memory CD4^+^ T cells and committed Th17 cells, through up-regulation of IL-9 ([@B55]). Nevertheless, TL1A co-stimulation has been proven essential for both gut and cerebral immunopathology that depends on Th1 and Th17 in relevant mouse models ([@B36], [@B43], [@B50]). ### Tregs Control of proliferation and suppressive function of regulatory T cell (Treg) is another way through which the TL1A-DR3 system controls local immune responses. Tregs constitutively express DR3, and DR3 signaling has been found to enhance proliferation of Tregs partly by enhancing their responsiveness to IL-2 ([@B56]--[@B58]). The proliferative effect of TL1A on Tregs has been recently confirmed for human cells in ex vivo studies ([@B59]). However, TL1A inhibits Treg suppressive ability both directly and indirectly by rendering activated Teff cells resistant to Treg mediated suppression ([@B56], [@B57]). Removal of TL1A completely restores the suppressive ability of Tregs both in vitro and in vivo ([@B56], [@B58]). Given the transient nature of TL1A up-regulation by APCs, an accelerated effector T cell response could be accompanied by increased numbers of Tregs capable of controlling activated T cells when local concentrations of TL1A have decreased. These findings suggest the existence of an elegant operational system that promptly amplifies immune responses against invading pathogens and rigorously dampens immune activation once the pathogens is eliminated ([@B60]). Finally, the addition of TL1A in conventional T cells cultured under FoxP3-promoting conditions, inhibited iTreg differentiation ([@B57], [@B61]). Instead, forced overexpression of high levels TL1A by FoxP3-expressing T cells promoted proinflammatory characteristics such as the production of IL-4 and IL-13 ([@B61]). TL1A-overexpressing Tregs were unable to protect from colitis in the T cell transfer colitis model ([@B61]). However, transgenic Tregs expressing low levels of TL1A were able to suppress T cell transfer colitis, an effect dependent on DR3 signaling and associated with protective levels of IL-17 and TGFβ ([@B61]). The importance of this low level expression of TL1A for the maintenance of Treg populations and functions in the periphery remains to be elucidated. ### Th9 Cells Although the TL1A-DR3 system had no effect on Th1/Th2 polarization and a debated effect on Th17 differentiation, it recently became evident that it plays an important role for the generation of Th9 cells that are involved in defense against helminthes and allergy. On the one hand, TL1A co-stimulation enhances generation of Th9 T cells in the presence of TGFβ and IL-4, conditions that favor Th9 differentiation ([@B62]). On the other hand, in the presence of TGFβ and IL-2, conditions that favor iTreg generation, TL1A diverts the differentiation of iTregs to Th9 cells ([@B62]). Interestingly, TL1A up-regulates IL-9 secretion though an alternative pathway that involves STAT5 activation by IL-2 instead of STAT6 activation by IL-4 ([@B62]). In vitro data have also been coupled by in vivo evidence of an increased pathogenicity of Th9 cells in the presence of TL1A in a model of Th9-dependent allergic ocular and lung inflammation ([@B62]). In addition to T cell dependent allergic lung inflammation, intact DR3 signaling has also been found important for ILC2 expansion and pathogenicity in innate models of allergic lung inflammation ([@B63]). Besides allergic immunopathology, TL1A-directed Th9 polarization, has been associated with CD4^+^-dependent anti-tumor responses. Dectin-1-activated dendritic cells, acting partly though TL1A-DR3, have been found to induce Th9 cells that enhance tumor-specific CTL activity against OVA-expressing melanoma tumors ([@B64]). ### Other Cell Populations TL1A co-stimulation enhances proliferation, IL-2 production, and cytotoxicity of DR3 expressing CD8+ T cells ([@B65]). Moreover, natural killer (NK) cells are capable of expressing DR3 after stimulation with IL-12 and IL-18, which led to enhanced IFNγ production and anti-tumor responses following TL1A stimulation ([@B51], [@B66]). Innate lymphoid cells (ILCs) also express DR3 and increase cytokine production upon TL1A stimulation ([@B63]). These findings indicate a broader role of TL1A/DR3 system in protective immunity. DR3 is also highly expressed on NKT cells. In this population, unlike in T cells, TL1A appears to promote a more restricted set of cytokines, enhancing IL-4 and IL-13 but not IFNγ production ([@B48]). B cells also express DR3, especially after polyclonal stimulation through the B-cell receptor ([@B67]). Plasma cells (but not B cells) also expressed very high levels of DR3 in a mouse model of collagen-induced arthritis ([@B68]). However, the role of TL1A/DR3 in B cell functions is not yet clear. Functional Roles of TL1A/DR3 in Mucosal Homeostasis and Inflammation -------------------------------------------------------------------- The original identification of TL1A in 2002 was followed by an abundance of studies that have largely brought about the significance of the TL1A/DR3 system in immunological responses, with particular emphasis in mucosal immunity pathways. Although originally presented as Th1 polarizing molecules, TL1A and DR3 were soon proved to display a vast array of multiple and even opposite immune functions that are critically dependent on the particular clinical or experimental scenario. In this process the contribution of genetically manipulated murine models and the application of neutralizing or stimulatory monoclonal antibodies have been of paramount importance ([Table 2](#T2){ref-type="table"}). ###### Effects of genetic or immunological manipulation of TL1A/DR3 expression. --------------------------------------------------------------------------------------------------------------------------------------------------------------------- Model TL1A Tx TL1A-Tg TL1A ko DR3 ko Anti-TL1A References --------------------------------------------------- ------------- -------------- ------------------ --------------------- ---------------- -------------------------- Spontaneous phenotype Ileitis, TH2 ([@B56], [@B57], [@B69]) DSS Worsening Worsening ⇓ Chronic ([@B36], [@B70]) TNBS ⇓ Weight loss\ ([@B57]) ⇓ Histology SAMP ileitis Protected Gai2 ko transfer ⇓ Weight loss\ ([@B36]) ⇓ Histology Experimental allergic encephalomyelitis (EAE) ⇓ Clinical score ⇓ Clinical score ([@B43], [@B50]) Collagen-induced arthritis (CIA) Worsening Protected ([@B71]) Antigen-induced arthritis (AIA) Worsening ⇓ Chronic arthritis Protected ([@B71]) Ovalbumin (Ova) lung hypersensitivity pneumonitis Protected Protected ([@B43], [@B62]) --------------------------------------------------------------------------------------------------------------------------------------------------------------------- ### Protective Functions During Acute Injury and Repair: The Role of TL1A/DR3 in Innate Immunity Recent studies have provided evidence for a protective role of TL1A/DR3 in host defense against acute harmful stimuli. Buchan et al. demonstrated expression of TL1A by F4/80^+^ macrophages in the spleen of mice during Salmonella enterica Typhimurium infection ([@B72]). In the same model, DR3 signaling was essential for optimal expansion of activated/memory CD4^+^ T cells that produced IFNγ and facilitated bacterial clearance ([@B70], [@B72]). Similarly, in the absence of DR3 signaling, early antiviral immunity against murine cytomegalovirus was impaired and fewer virus-specific CD4+ and CD8+ cells were generated, resulting in increased viral loads ([@B73]). A recent study by Pham et al. further showed that DR3 signaling is essential for non-cognate stimulation of Th1 cells and effective elimination of intracellular bacteria in mice ([@B74]). Studies on human memory T cells have also shown that TL1A and IL-15 synergize to enhance proinflammatory cytokine production independently of cognate TCR--MHC-II interactions ([@B52]). They describe a significant population of memory CD4^+^ T cells characterized by the expression of IL-18R and DR3 and located preferentially in mucosal surfaces such as the small intestine, the colon, the nasal mucosa and the skin. Stimulation with TL1A/IL-15 induced strong IFNγ responses accompanied by production of IL-6, TNF-α, GM-CSF, IL-5, IL-13, and IL-22 with concomitant suppression of IL-10 production. These findings imply that TL1A/DR3 supports the innate activity of mucosal memory T cells. Whether these cells exert protective mucosal roles during acute inflammation, however, remains to be shown. On the other hand, identification of large numbers of these IL-18Rα^+^DR3^+^ T cells has been reported in the small bowel of CD patients. This rather indicates a primary pathogenetic/proinflammatory role for TL1A in chronic autoimmune intestinal inflammation ([@B74]). Further support for an important role of TL1A/DR3 signaling in mucosal homeostasis arose from the recent discovery of the stimulatory effect of TL1A on innate lymphoid cells (ILCs). Type 2 cells (ILC2) at mucosal surfaces may depend on TL1A/DR3 signaling, as high DR3 expression was detected in both human and murine ILC2. Stimulation with TL1A resulted in enhanced expansion, survival, and function of ILC2 ([@B75]). More importantly, this effect was independent of the critical ILC2 regulators IL-25 and IL-33. The biological significance of these experimental findings were substantiated by the increased susceptibility of DR3^−/−^ lymphopenic mice to gut helminthic infections ([@B75]) and their failure to develop lung responses to nasal challenge with papain ([@B75]). Finally, Meylan et al. reported that TL1A-dependent co-stimulation of ILC2 was involved in experimental allergic lung disease ([@B63]). Group 3 ILCs are defined by their expression of RORγt^+^ and ability to produce IL-17 and IL-22 ([@B76]). They reside mostly at the intestinal mucosa to enhance intestinal barrier integrity and epithelial repair primarily through the production of their signature cytokine IL-22 ([@B77]). ILC3-derived IL-22 is critical for constraining commensal bacteria and protecting against pathogenic bacteria and viruses via the regulation of intestinal anti-microbial peptides and B cell responses ([@B78]--[@B84]). TL1A is one of the intermediate messengers of innate immune responses produced by ILC3s that rescue mice from C. rodentium--induced colitis. Specifically, bacterial sensing CX3CR1^+^ mononuclear phagocytes in the intestinal lamina propria produce TL1A, IL-1β, and IL-23 that upregulate production of IL-22 from intestinal ILC3s and protect against infectious colitis and dextran sodium sulfate (DSS)-mediated acute colitis ([@B38], [@B85]). Up-regulation of IL-22 production was depended on DR3 signaling in both mouse and human ILC3 that constitutively express this receptor ([@B85], [@B86]). Furthermore, the combination of IL-1β, IL-23 and TL1A, induced the expression of CD25 on human ILC3 cells to enhance IL-2-mediated proliferation ([@B86]). Collectively, the above findings indicate that TL1A/DR3 have a major role in orchestrating innate immunity pathways in the intestine by the regulation of the local ILC3 pool and cytokine production. The role of TL1A/DR3 in preserving mucosal homeostasis was shown with the use of TL1A- and DR3-deficient mice ([@B70]). DSS-colitis was more severe in the absence of either TL1A or DR3, indicating protective roles for these proteins during acute mucosal injury and repair. This was associated with a compromised ability to maintain adequate numbers of Foxp3^+^ regulatory T cells in the periphery and inability to restrain Th17 immune responses. Similar results have been observed in the T cell transfer model, where intact DR3 signaling and a low level of TL1A expression on Foxp3^+^ regulatory T cells was required to maintain their suppressive function and rescue from colitis ([@B61]). It should be noted, however, that in the DSS model the effects of TL1A and DR3 deficiency were not identical as there were differences between the two cases in regards to mortality and kinetics of inflammatory responses ([@B70]). However, Castellanos et al have failed to detect significant differences in Foxp3^+^ T regulatory or IL-17-producing RORγt^+^ (Th17) cells during acute colitis in DR3-deficient mice ([@B38]). Using mice with ILC3 specific DR3 deletion (DR3^ΔILC3^) they showed that exacerbation of DSS colitis was due to the downregulation of IL-22 production by ILC3s, whereas treatment with recombinant IL-22 rescued survival of DR3^ΔILC3^ mice ([@B38]). ### Pro-inflammatory Functions During Chronic Inflammation: The Role of TL1A/DR3 in Adaptive Immunity Many studies during the last decade have demonstrated that the TL1A/DR3 system is up-regulated in patients with IBD and chronic intestinal inflammation. Gut tissue specimens from CD and UC patients exhibit increased TL1A transcripts and protein expression, which correlated with the severity of tissue inflammation. Paired samples of macroscopically uninvolved intestine from the same patients had intermediate levels of TL1A, and minimal or un-detectable amounts were observed in healthy controls ([@B37], [@B49]). Recent studies have correlated the increase of TL1A transcripts at the colonic mucosa of IBD patients to the levels of IL-17A expression ([@B87]). Immunohistochemical studies and cytometric analysis on isolated cells from the lamina propria further specified that the increased amounts of TL1A detected in IBD tissue were derived from infiltrating lymphocytes and intestinal macrophages in CD and plasma cells in UC. A similar pattern of expression, which correlated with disease activity, was observed for DR3 ([@B37], [@B49]). Furthermore, systemic levels of TL1A and its decoy receptor DcR3 parallel disease activity in colonic CD and UC. Recently, a significant correlation of the expression of DR3 on peripheral blood mononuclear cells with CRP levels was observed in newly diagnosed children and adults with IBD ([@B88]). Both local expression and systemic levels were found to decrease following effective treatment ([@B88]--[@B90]). Studies in animal models with transgenic expression of TL1A provided more mechanistic insights about the possible involvement of TL1A in IBD. Mice with forced constitutive expression of TNFSF15 (TL1A-tg) in either the lymphoid or myeloid cell compartments demonstrated a stable phenotype of mild ileitis ([@B56], [@B57], [@B69]). All transgenic mice developed inflammatory changes in the terminal ileum that included disrupted villi architecture, infiltration of the lamina propria with inflammatory cells, goblet cell hyperplasia and thickening of the muscularis propria. Inflammatory changes were accompanied by lengthening of the small intestine and failure to gain weight. The patchy distribution of the inflammatory lesions and the development of intestinal fibrosis are two characteristics shared with human CD. Small bowel pathology was associated with increase in activated T cells and regulatory Foxp3^+^CD4^+^ T cells. The most prominent feature was a predominant Th2 mucosal response. Indeed, TL1A-Tg mice displayed elevations in mucosal IL-13 and IL-5 mRNA content, whereas, blockade of IL-13 ameliorated the severity of ileitis ([@B56], [@B57], [@B69]). The striking resemblance of the TL1A--induced pathology to intestinal anti-parasitic responses led the investigators to further study the role of TL1A in this field. They subsequently observed that TL1A can stimulate IL-13 production by Group 2 Innate lymphoid cells, an effect mediated via DR3 ([@B63]). However, the TL1A-dependent innate pathway they identified was not required for effective intestinal anti-parasitic responses but mostly played a major role in allergic lung pathology in relevant murine models ([@B63]). It is now widely accepted that Th2 predominant immunity is a characteristic of the late maintenance stages of clinical and experimental IBD, as it was shown in great detail in CD-like ileitis in SAMP1/YitFc mice ([@B91]--[@B94]). Interestingly, both TL1A-Tg and SAMP1/YitFc mice develop small intestinal inflammation, marked hypertrophy of the muscular layer, and high mucosal expression of IL-13 and IL-5. Additionally, mucosal TL1A mRNA expression is also upregulated in the chronic phase of SAMP1/YitFc ileitis ([@B35]). These studies raise the possibility that the proinflammatory function of TL1A may be partially mediated through induction of Th2/IL-13 dependent mucosal responses, which are now recognized as central pathogenetic factors in IBD. The importance of TL1A/DR3 in murine colitis has also been investigated in the TNBS, DSS and the G-protein ai2 deficient models ([@B36], [@B57]). Development of colitis was associated with mucosal upregulation of TL1A and DR3 and colitis was effectively prevented or attenuated by the administration of anti-TL1A neutralizing antibodies. Taken together, mucosal overexpression of TL1A (primary or secondary) may be implicated in the induction of pathogenetic effector proinflammatory pathways. A functional dichotomy between membrane and soluble forms of TL1A may also occur, as it was shown recently. Using a membrane restricted TL1A transgenic mouse Ferdinand et al., have shown that increased production of soluble TL1A, possibly by APCs, was required to produce maximal small bowel pathology. In contrast membrane bound TL1A, mostly of T-cell localization, was required to elicit inflammatory responses including IL-13, IL-17, and IL-9 production in murine lungs ([@B95]). DR3 and TL1Ako mice do not develop any gross abnormalities. Nevertheless, immunological characterization of these strains detected specific defects that may be of interest. It was shown that DCs from TL1A^−/−^ mice fail to support the differentiation and proliferation of Th17 lymphocytes ([@B50]). Consistently, these mice were protected from Th17-mediated inflammation in a model of Experimental Autoimmune Encephalomyelitis ([@B43], [@B50]). Similarly DR3 signaling was required for Th2-mediated lung immunopathology in an Ova model of allergic lung inflammation ([@B43]). TL1A deficiency has also been reported to induce broader changes on the gut immune microenvironment, such as marked decrease of intraepithelial TCRγδ^+^ and CD8^+^ lymphocytes and reduced expression of the activating receptor NKG2D ([@B96]). Quite unexpectedly, there were also significant changes in gut microbial composition with significantly suppressed cecal Clostridium cluster IV, altered cecal Firmicutes/Bacteroidetes ratio, and reduction in ileal Lactobacillus spp. This was also associated with reduced body weight, and decreased size of adipose tissue and adipokine expression ([@B96]). The latter raise the possibility that TL1A may affect microbiota-related metabolic pathways that regulate adipose tissue development. Collectively, the above data support an important role for the TL1A/DR3 system in the maintenance of mucosal homeostasis and a significant contribution, when unrestrained, to late IBD-related immunopathology. Mechanistic evidence for the implication of TL1A/DR3 signaling in the effector pathways that mediate chronic inflammation was recently presented by Li et al. ([@B97]) who tested the effect of DR3 stimulation of DR3 deletion in the ileitis-prone SAMP1/YitFc mouse model of CD. They, first, showed that administration of an agonistic antibody against DR3 (4C12) prior to disease development markedly worsened the severity of ileitis in SAMP mice. The immunological effects of DR3 stimulation included overproduction of T~H~1 and T~H~2 cytokines, expansion of dysfunctional CD25^−^FoxP3^+^ and ILC1 cells, and concomitant reduction of CD25^+^FoxP3^+^ and ILC3 cells. By comparison, genetic deletion of DR3 effectively reversed the inflammatory phenotype in SAMP mice. This was associated with selective expansion of CD25^+^FoxP3^+^ over CD25^−^FoxP3^+^ cells and upregulation of IL-10. These data demonstrate a central, multicellular modulation of adaptive immunity by DR3, via the regulation of the relative abundance of T~regs~, T effectors, and ILCs, which, subsequently, dictates the progression of CD-like ileitis in SAMP mice. More recently, Castellanos et al., have shown that TL1A induced ILC3 expression of OX40L in MHCII^+^ ILC3s that supports pathogenic T cell responses in the T-cell depended colitis transfer model. ILC3-spesific deletion of DR3 protected mice from the development of colitis ([@B38]). It follows that modification of DR3 signaling holds promise toward being an effective means for restoring the immunological balance between protective and inflammatory lymphocytes at the intestinal mucosa. TL1A/DR3 as Mediators of Fibrosis --------------------------------- Fibrosis refers to the process of excessive accumulation of extracellular matrix due to increased connective tissue assembly and ineffective matrix remodeling. Mostly, but not always, it represents the end result of repeated cycles of tissue inflammation, ulceration, and repair that ultimately lead to scarring and decline in organ function ([@B98]). Despite the wealth of knowledge of inflammatory pathways that have resulted in largely effective anti-inflammatory biologic treatment for various autoimmune diseases, including IBD, the fibrogenetic cascades that result to tissue scarring remain relatively understudied and effective therapies to prevent or, more importantly, reverse fibrotic processes are currently lacking ([@B99]). TL1A amplifies multiple immunological pathways that, when sustained, could be associated with the development of fibrosis. Interleukin 17A favors the development of fibrosis in experimental models of lung and skin fibrosis and has been found to be overexpressed in intestinal strictures of CD patients ([@B100], [@B101]). IL-13 has been implicated in murine experimental intestinal fibrosis, acting mostly through TGFβ, and also is upregulated in strictures of patients with CD ([@B102], [@B103]). Finally, TL1A-induced expansion of Treg populations with altered function in the periphery may theoretically promote local saturation with IL-13 and, most importantly, TGFβ, which is the key regulator of pro-fibrotic pathways and a major activator of mesenchymal cells ([@B104]). Interestingly, elevated TL1A and DR3 expression has been found in the SAMP1/YitFc model of murine ileitis that is phenotypically associated with the development of overt intestinal strictures ([@B35]). TL1A transgenic mice develop IL-13-dependent inflammation of the small bowel ([@B57]). Phenotypically, TL1A-tg mice are characterized by small bowel wall thickening, especially at the terminal ileum, which is the usual site of stricture development in human CD. Pathology was characterized by enhanced infiltration of the lamina propria with inflammatory cells, increase of the numbers and size of goblet and Paneth cells and hypertrophy of the muscularis propria ([@B56], [@B57]). These changes were accompanied by increased expression of IL-5, IL-13, and IL-17 by intestinal tissue and mesenteric lymph nodes. Another set of studies by a different group on transgenic mice that constitutively expressed TL1A on the lymphoid or myeloid compartment have demonstrated a similar phenotype characterized by ileitis and Paneth cell hyperplasia ([@B69]). However, they further describe increased accumulation of collagen in intestinal tissue. Examination of the same transgenic mice under colitogenic conditions, in the context of the DSS and the adoptive T cell transfer model, revealed the development of overt intestinal strictures at the small and the proximal large bowel ([@B105]). The fibrotic phenotype was associated with increased local expression of TGFβ and IGF in colitic mice. Interestingly, constitutive production of TL1A was associated with relative expansion of CD4^+^IL17^+^ effector T cells in the mesenteric lymph nodes in the DSS by not in the adoptive T cell transfer model. This may indicate that diverse, TL1A-mediated profibrotic immunological pathways may dominate depending on the colitogenic conditions. Further studies by the same group demonstrated that treatment with antibodies against TL1A was capable to reduce inflammation and to reverse fibrosis in both DSS and adoptive transfer model even when treatment was administrated late in the course of disease, that is after inflammation and fibrosis had been established ([@B106]). Anti-TL1A treatment decreased expression of pro-fibrotic molecules such as IGF1, CTGF, and TIMP1 in the inflamed intestinal tissue. Furthermore, mucosal expression of DR3 was associated with fibrotic changes in the bowel wall and DR3^−/−^ mice exhibited reduced numbers of intestinal fibroblasts and myofibroblasts. Intestinal myofibroblasts responded to TL1A with increased expression of Col1a2 and IL-31Ra, a myofibroblast activation marker. Finally, neutralization of TL1A reduced expression of a-SMA and vimentin, activation markers of colonic fibroblasts, and expression of TGFβ1 and Smad3 in the colonic tissue of adoptively T cell transferred colitic mice ([@B107]). However, only a subset (25%) of intestinal myofibroblasts expressed DR3, and the relative contribution of the TL1A/DR3 system on fibrosis independent of its anti-inflammatory effects was not explored. Despite this, these studies demonstrated for the first time that an anti-inflammatory therapy, in this case TL1A neutralization, can not only prevent but also potentially reverse established intestinal fibrosis. This is especially important for human CD which often has a long indolent course resulting in both inflammatory and fibrostenotic segments of the small bowel on initial patient presentation and disease diagnosis. A recent study by Jacob et al., suggests that the pro-fibrotic effects of TL1A on bowel mucosa may depend on the composition of the intestinal microflora ([@B108]). TL1A-Tg mice raised under germ-free condition were protected from spontaneous ileitis and cecal collagen deposition. A direct effect of the host microflora was demonstrated on colonic fibroblasts exhibiting enhanced migration/proliferation and collagen production when derived from specific pathogen free as opposed to germ free littermates, and on wild type fibroblasts exposed to specific pathogen free microflora. Interestingly, gnotobiotic TL1A-Tg mice colonized with human gut microflora were protected from both ileitis and cecal fibrosis. Through 16S rRNA sequencing characterization of ileal and cecal microbiome the authors were able to depict possible bacterial genera and species that differentially promote fibrosis in the respective localizations in the context of TL1A overexpression ([@B108]). In human fibrotic conditions, including IBD, the immunological and profibrotic cascades driven by TL1A remain underexplored. The potential implication of TL1A in such pathways was recently highlighted by the report of TL1A expression by human intestinal myofibroblasts that were isolated from IBD patients ([@B109]). TL1A expression by intestinal myofibroblasts was up-regulated by pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1α) or supernatants of intestinal tissue cultures from IBD patients ([@B109]). The same pro-inflammatory cytokines induced expression of DR3 and DcR3 on cultured epithelial cells, whereas, supernatants from cultures of stimulated epithelial cells were capable to induce upregulation of TL1A in intestinal myofibroblasts. Similar findings have been reported for lung fibrosis and indicate the existence of additional TL1A-dependent possibly pro-fibrotic cascades mediated by epithelial/stromal cell interactions ([@B110]). These results point to the existence of a mucosal amplification loop that is initiated by the local pro-inflammatory milieu and then perpetuates itself through reciprocal stimulation of epithelial cell and intestinal myofibroblasts. Nevertheless, whether such interaction leads to increased collagen accumulation and fibrosis remains to be shown. An approach toward the elucidation of the relative contribution of TL1A/DR3 signaling in intestinal fibrosis independently from its role in inflammatory cascades would be the generation and study of conditional DR3 and TL1A knockout mice with tissue specific TL1A and DR3 deficiency on intestinal fibroblasts or epithelial cells ([@B106]). TL1A/DR3 in the Crossroads of Systemic Inflammation: Associations With Extraintestinal Inflammation {#s4} =================================================================================================== The TL1A/DR3 pathway is considered one of the common denominators in various pathologies associated with inflammation in different tissues that develops through aberrant immune responses. Genetic studies support its implication in autoimmune diseases and mycobacterial infections. Case-control and GWA studies have identified Tnfsf15 gene variants, such as rs6478108 alleles, that associate with increased susceptibility to psoriasis and psoriatic arthritis in populations of European descent ([@B111], [@B112]). Furthermore, alleles rs6478108 (T) and rs4979462 (T), have been found to increase susceptibility to both Primary Billiary Cholangitis (PBC) and CD, while protecting from leprosy ([@B6], [@B113]). Moreover, the rs6478108 (G) allele has been associated with increased risk for CD and the pathological inflammatory host response in leprosy known as Type 1 reaction ([@B114], [@B115]). Further genetic evidence links the TL1A/DR3 pathway to major extraintestinal manifestations of IBD. Indeed, genetic variation in the Tnfsf15 gene has been associated with increased susceptibility in spondyloarthropathies, ankylosing spondylitis, and anterior uveitis ([@B116]--[@B118]). Similarly to intestinal inflammation, increased TL1A was found in the serum of patients with rheumatoid arthritis and ankylosing spondylitis and also correlated with disease activity in both conditions ([@B41], [@B119]). More importantly, TL1A levels are decreased following treatment with anti-TNF. Local levels of TL1A have also been found increased in rheumatoid arthritis with mononuclear phagocytes being the major source of TL1A in the synovial tissue and synovial fluid of rheumatoid factor positive patients ([@B40]). In murine models of antigen induced arthritis and collagen induced arthritis TL1A administration promoted osteclastogenesis and exacerbated disease, whereas anti-TL1A ameliorated pathology ([@B71]). TL1A effects were found to be DR3-dependent as DR3^−/−^ mice were protected from cartilage depletion and joint destruction. This was partly attributed to decreased production of CXCL1 in the joints of DR3^−/−^ mice and the relative reduction of infiltrating neutrophil numbers which correlated with decreased local levels of MMP-9 ([@B120]). Psoriasis is a common concomitant immune-mediated disorder in patients with IBD. Psoriasis and IBD share pathogenetic pathways such as the IL-23/IL-17 pathway, have common genetic risk alleles and are associated with abnormalities in intestinal and skin microflora and both respond to anti-TNF and anti-p40 treatment ([@B121]). There is evidence that TL1A/DR3 may represent an additional pro-inflammatory pathway that is shared between the two diseases. TL1A and DR3 have been found to be increased in psoriatic skin lesions and specifically in macrophages and keratinocytes ([@B122]). TL1A seems to synergize with IL-23 to stimulate PMBCs from patients with psoriasis to increase production of IL-17 ([@B123]). Uveitis is another extraintestinal manifestation of IBD that has been associated with the TL1A/DR3 pathway. Specifically, experimental murine autoimmune uveoretinitis was dependent on DR3 as DR3^−/−^ mice are protected from disease development ([@B124]). Although a direct association of TL1A/DR3 with the extraintestinal manifestations of IBD has not been established yet, there is indirect evidence that such an association may exist making TL1A/DR3 a possible common denominator of the gut-skin-joint-eye autoimmune inflammation axis. Concluding Remarks {#s5} ================== Since its initial description, TL1A has arisen as an important mucosal factor that is implicated in homeostasis and inflammation through its association with DR3. In the light of translational medicine, it is important that this role of TL1A/DR3 is supported by converging lines of evidence. In particular, polymorphisms in Tnfsf15 significantly affect susceptibility to IBD and may be associated with altered function of the respective protein. In addition, there is significant upregulation and abundant expression of TL1A and DR3 in inflammatory conditions that affect the intestines, mainly IBD. So far, functional properties of the TL1A/DR3 system involve several immunological pathways that are considered important in the pathogenesis of IBD. Finally, the proof of concept for the therapeutic application of TL1A/DR3 modification has been fulfilled in animal models of intestinal inflammation. In all, it could be said that the system of TL1A/DR3 may represent a desirable therapeutic target for a subset of IBD patients. Nevertheless, caution is also required as important questions remain unanswered still. One area of concern is the potential effect on Tregs. As TL1A/DR3 have positive effects on Treg function, their neutralization may compromise this population and jeopardize its important anti-inflammatory function in intestinal immunity. A second question is whether blockade of TL1A or DR3 should be the preferable approach in clinical practice. This is of importance as recent evidence from animal models of inflammation reported similar but not identical effects of genetic or immunologic deletion of the two molecules. Finally, antibodies against DR3 have shown agonistic effects which depend on the target population. All these parameters should be taken into account for the design of clinical trials that aim to disrupt TL1A/DR3 signaling. Author Contributions {#s6} ==================== VV, GK, and GB all contributed to the development of the concept of the review, performed the literature review and analyzed existing data, and wrote and edited the manuscript. 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. [^1]: Edited by: Detlef Neumann, Hannover Medical School, Germany [^2]: Reviewed by: Piergiuseppe De Berardinis, Istituto di Biochimica delle Proteine (IBP), Italy; Guntram A. Grassl, Hannover Medical School, Germany [^3]: This article was submitted to Cytokines and Soluble Mediators in Immunity, a section of the journal Frontiers in Immunology
FREE now and never miss the top politics stories again. SUBSCRIBE Invalid email Sign up fornow and never miss the top politics stories again. We will use your email address only for sending you newsletters. Please see our Privacy Notice for details of your data protection rights. The measure features in a parliamentary report into behaviour that infringes on “the freedom of movement of women in public spaces and undermines self-esteem and the right to security”. The plans come from a parliamentary working group on street harassment launched by gender equality minister Marlene Schiappa. The bill is expected to be presented to parliament next week after Ms Schiappa and two other ministers - Minister of Justice, Nicole Belloubet, and Minister of the Interior, Gerard Collomb - read the final draft. GETTY French gender equality minister Marlene Schiappa Ms Schiappa said in September new measures were needed to address the “grey zone between consented seduction and sexual aggression”. Politicians have been putting their heads together for a report on how to tackle the issue and define what constitutes “sexual outrage”. This has been the foundation of the plans drawn up to eradicate what is described as everyday sexism in France. GETTY Marlene Schiappa wants to introduce on-the-spot fines for harrassment Men who make loud and lewd comments about women, follow them or block their path could be fined, according to measures suggested in the report. The parliamentary group suggested imposing a £80 (€90) fine on those who pay immediately, increasing to £170 (€195) if it is paid within 15 days and £300 (€350) if the payment is later than that. It did not recommend impose fines for wolf-whistling contrary to earlier reports. GETTY Authorities in Paris have already announced a new measure to tackle harassment on public transport
Q: How to invoke the Pod proxy verb using the Kubernetes Go client? The Kubernetes remote API allows HTTP access to arbitrary pod ports using the proxy verb, that is, using an API path of /api/v1/namespaces/{namespace}/pods/{name}/proxy. The Python client offers corev1.connect_get_namespaced_pod_proxy_with_path() to invoke the above proxy verb. Despite reading, browsing, and searching the Kubernetes client-go for some time, I'm still lost how to do the same with the goclient what I'm able to do with the python client. My other impression is that I may need to dive down into the rest client of the client changeset, if there's no ready-made API corev1 call available? How do I correctly construct the GET call using the rest client and the path mentioned above? A: As it turned out after an involved dive into the Kubernetes client sources, accessing the proxy verb is only possible when going down to the level of the RESTClient and then building the GET/... request by hand. The following code shows this in form of a fully working example: package main import ( "fmt" "k8s.io/client-go/kubernetes" "k8s.io/client-go/tools/clientcmd" ) func main() { clcfg, err := clientcmd.NewDefaultClientConfigLoadingRules().Load() if err != nil { panic(err.Error()) } restcfg, err := clientcmd.NewNonInteractiveClientConfig( *clcfg, "", &clientcmd.ConfigOverrides{}, nil).ClientConfig() if err != nil { panic(err.Error()) } clientset, err := kubernetes.NewForConfig(restcfg) res := clientset.CoreV1().RESTClient().Get(). Namespace("default"). Resource("pods"). Name("hello-world:8000"). SubResource("proxy"). // The server URL path, without leading "/" goes here... Suffix("index.html"). Do() if err != nil { panic(err.Error()) } rawbody, err := res.Raw() if err != nil { panic(err.Error()) } fmt.Print(string(rawbody)) } You can test this, for instance, on a local kind cluster (Kubernetes in Docker). The following commands spin up a kind cluster, prime the only node with the required hello-world webserver, and then tell Kubernetes to start the pod with said hello-world webserver. kind create cluster docker pull crccheck/hello-world docker tag crccheck/hello-world crccheck/hello-world:current kind load docker-image crccheck/hello-world:current kubectl run hello-world --image=crccheck/hello-world:current --port=8000 --restart=Never --image-pull-policy=Never Now run the example: export KUBECONFIG=~/.kube/kind-config-kind; go run . It then should show this ASCII art: <xmp> Hello World ## . ## ## ## == ## ## ## ## ## === /""""""""""""""""\___/ === ~~~ {~~ ~~~~ ~~~ ~~~~ ~~ ~ / ===- ~~~ \______ o _,/ \ \ _,' `'--.._\..--'' </xmp>
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repeatedly dosed versus fresh soils where antibiotics were never appl...They did this experiment Topp explains because of previous work indi...Still it came as a surprise when they saw antibiotics also degrading ...The researchers subsequently cultured from the treated plots a new str...Taken together the findings suggest that the capability to break down... repeatedly dosed, versus fresh soils where antibiotics were never applied. They did this experiment, Topp explains, because of previous work indicating that pesticides often break down more quickly in soils with a long history of exposure, indicating that pesticide-degrading microbes have been selected for over time. Still, it came as a surprise when they saw antibiotics also degrading much faster in long-term, treated plots than in fresh, control soils, he says. In particular, sulfamethazinea member of the antibiotic class called sulfonamidesdisappeared up to five times faster. The researchers subsequently cultured from the treated plots a new strain of Microbacterium, an actinomycete that uses sulfamethazine as a nitrogen and carbon source. Extremely common in soil, actinomycete bacteria are known to degrade a wide range of organic compounds. And now at least two other sulfanomide-degrading Microbacterium strains have been reported, Topp says: one from soil and another from a sewage treatment plant. Taken together, the findings suggest that the capability to break down sulfanomides could be widespread. And if it's indeed true that "the microbiology in the environment is learning to break these drugs down more rapidly when exposed to them, this would effectively reduce the amount of time that the environment is exposed to these drugs and therefore possibly attenuate the impacts," Topp says. Not that negative impacts aren't still occurring, he cautions. In particular, long-term exposure to antibiotics puts significant pressure on soil bacteria to evolve resistance, which they typically do by giving and receiving genes that let them detoxify drugs, or keep the compounds out of their cells. What the new research suggests, though, is that soil bacteria could be swapping genes for breaking down antibiotics at the same time. "My guess is that's probably what's happening, but it remains to be det'/>"/> (Date:7/31/2015)... , July 31, 2015 The 10 th ... held by BGI from October 22-25, 2015, in Shenzhen ... The conference is celebrating its 10 th anniversary this year. ... the world,s most influential annual meetings in the ,omics, fields, ... scientific gatherings. ICG-10 focuses on recent breakthroughs ... ... the Susquehanna River just above Chesapeake Bay are nearly at ... large storms are already delivering increasingly more suspended sediment and ... 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/* * Copyright (C) 2011-2012 Dr. John Lindsay <jlindsay@uoguelph.ca> * * This program is free software: you can redistribute it and/or modify * it under the terms of the GNU General Public License as published by * the Free Software Foundation, either version 3 of the License, or * (at your option) any later version. * * This program is distributed in the hope that it will be useful, * but WITHOUT ANY WARRANTY; without even the implied warranty of * MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the * GNU General Public License for more details. * * You should have received a copy of the GNU General Public License * along with this program. If not, see <http://www.gnu.org/licenses/>. / package plugins; import java.awt.BorderLayout; import java.awt.Color; import java.awt.Container; import java.awt.Dimension; import java.awt.event.ActionEvent; import java.awt.event.ActionListener; import java.awt.event.ItemEvent; import java.awt.event.ItemListener; import java.beans.PropertyChangeEvent; import java.beans.PropertyChangeListener; import java.util.Date; import java.io.File; import javax.swing.; import java.util.ResourceBundle; import whitebox.geospatialfiles.WhiteboxRaster; import whitebox.geospatialfiles.WhiteboxRasterInfo; import whitebox.geospatialfiles.ShapeFile; import whitebox.geospatialfiles.shapefile.; import whitebox.interfaces.WhiteboxPlugin; import whitebox.interfaces.WhiteboxPluginHost; import whitebox.interfaces.Communicator; import whitebox.ui.ComboBoxProperty; import whitebox.ui.plugin_dialog.DialogFile; import whitebox.internationalization.WhiteboxInternationalizationTools; import whitebox.georeference.Ellipsoid; import whitebox.georeference.LL2UTM; import whitebox.georeference.UTM2LL; import static whitebox.geospatialfiles.shapefile.ShapeType.; import whitebox.utilities.FileUtilities; import whitebox.interfaces.ThreadListener; /** * This tool can be used to convert raster data that is in geographic coordinates (latitude and longitude) into the UTM projected coordinate system or vice versa. * * @author Dr. John Lindsay email: jlindsay@uoguelph.ca / public class CoordinateSystemTransformation implements WhiteboxPlugin { private WhiteboxPluginHost myHost; private String[] args; private CoordinateTransformDialog panel = new CoordinateTransformDialog(); /* * Used to retrieve the plugin tool's name. This is a short, unique name * containing no spaces. * * @return String containing plugin name. / @Override public String getName() { return "CoordinateSystemTransformation"; } /* * Used to retrieve the plugin tool's descriptive name. This can be a longer * name (containing spaces) and is used in the interface to list the tool. * * @return String containing the plugin descriptive name. / @Override public String getDescriptiveName() { return "Coordinate System Transformation"; } /* * Used to retrieve a short description of what the plugin tool does. * * @return String containing the plugin's description. / @Override public String getToolDescription() { return "Converts an image between coordinate systems."; } /* * Used to identify which toolboxes this plugin tool should be listed in. * * @return Array of Strings. / @Override public String[] getToolbox() { String[] ret = {"ConversionTools"}; return ret; } /* * Sets the WhiteboxPluginHost to which the plugin tool is tied. This is the * class that the plugin will send all feedback messages, progress updates, * and return objects. * * @param host The WhiteboxPluginHost that called the plugin tool. / @Override public void setPluginHost(WhiteboxPluginHost host) { myHost = host; } /* * Used to communicate feedback pop-up messages between a plugin tool and * the main Whitebox user-interface. * * @param feedback String containing the text to display. / private void showFeedback(String feedback) { if (myHost != null) { myHost.showFeedback(feedback); } else { System.out.println(feedback); } } /* * Used to communicate a return object from a plugin tool to the main * Whitebox user-interface. * * @return Object, such as an output WhiteboxRaster. / private void returnData(Object ret) { if (myHost != null) { myHost.returnData(ret); } } /* * Used to communicate a progress update between a plugin tool and the main * Whitebox user interface. * * @param progressLabel A String to use for the progress label. * @param progress Float containing the progress value (between 0 and 100). / private void updateProgress(String progressLabel, int progress) { if (myHost != null) { myHost.updateProgress(progressLabel, progress); } else { System.out.println(progressLabel + " " + progress + "%"); } } /* * Used to communicate a progress update between a plugin tool and the main * Whitebox user interface. * * @param progress Float containing the progress value (between 0 and 100). / private void updateProgress(int progress) { if (myHost != null) { myHost.updateProgress(progress); } else { System.out.println("Progress: " + progress + "%"); } } /* * Sets the arguments (parameters) used by the plugin. * * @param args An array of string arguments. / @Override public void setArgs(String[] args) { this.args = args.clone(); } private boolean cancelOp = false; /* * Used to communicate a cancel operation from the Whitebox GUI. * * @param cancel Set to true if the plugin should be canceled. / @Override public void setCancelOp(boolean cancel) { //cancelOp = cancel; //if (cancel) { panel.cancelOperation(); //} } private void cancelOperation() { showFeedback("Operation cancelled."); updateProgress("Progress: ", 0); } private boolean amIActive = false; /* * Used by the Whitebox GUI to tell if this plugin is still running. * * @return a boolean describing whether or not the plugin is actively being * used. / @Override public boolean isActive() { return amIActive; } /* * Used to execute this plugin tool. / @Override public void run() { amIActive = true; //returnData(new CoordinateTransformDialog()); panel = new CoordinateTransformDialog(myHost); if (myHost instanceof JFrame) { JDialog dialog = new JDialog((JFrame) myHost, "Coordinate System Transformation", false); Container contentPane = dialog.getContentPane(); contentPane.add(panel, BorderLayout.CENTER); dialog.setDefaultCloseOperation(JFrame.DISPOSE_ON_CLOSE); dialog.pack(); dialog.setLocationRelativeTo(null); dialog.setVisible(true); } else { JFrame frame = new JFrame("Coordinate System Transformation"); Container contentPane = frame.getContentPane(); contentPane.add(panel, BorderLayout.CENTER); frame.setDefaultCloseOperation(JFrame.DISPOSE_ON_CLOSE); frame.pack(); frame.setLocationRelativeTo(null); frame.setVisible(true); } } class CoordinateTransformDialog extends JPanel implements PropertyChangeListener, ThreadListener, ActionListener { private Thread thread; private ResourceBundle bundle; private Ellipsoid ellipsoid = Ellipsoid.WGS_84; private DialogFile dfIn; private DialogFile dfOut; private JRadioButton ll2utmButton; private JRadioButton utm2llButton; private ComboBoxProperty interpolationChooser; private ComboBoxProperty ellipsoidChooser; private ComboBoxProperty zoneChooser; private JRadioButton northButton; private JRadioButton southButton; private JButton cancel; private JLabel spansUTMZones = new JLabel("Warning, the geographic extent spans multiple UTM zones."); private double north, south, east, west; private String projectionDirection = "ll2utm"; private String interpolationMethod = "nearest neighbour"; private int utmZoneNumber = 1; private String inputFile; private WhiteboxPluginHost host; public CoordinateTransformDialog() { } public CoordinateTransformDialog(WhiteboxPluginHost host) { this.host = host; initUi(); } private void initUi() { this.setName("Coordinate System Transformation"); // sets the title on it's dialog if (host == null) { bundle = WhiteboxInternationalizationTools.getGuiLabelsBundle(); host = new whitebox.plugins.PluginHost(); } else { bundle = host.getGuiLabelsBundle(); } Box mainBox = Box.createVerticalBox(); // input file args = new String[7]; args[0] = "inputFileDialog"; args[1] = "Input file"; args[2] = "Input File"; args[3] = "0"; // open mode args[4] = "true"; args[5] = "Whitebox Files (.shp; .dep), DEP, SHP"; args[6] = "false"; Communicator communicator = (Communicator) host; dfIn = new DialogFile(communicator); dfIn.setArgs(args); dfIn.addPropertyChangeListener("value", this); dfIn.setTextFieldActionListener(new ActionListener() { @Override public void actionPerformed(ActionEvent evt) { showFeedback("Hello"); } }); mainBox.add(dfIn); mainBox.add(Box.createVerticalStrut(5)); // output file args[0] = "outputFileDialog"; args[1] = "Output file"; args[2] = "Output File"; args[3] = "1"; // save mode args[4] = "true"; args[5] = "Whitebox Files (.shp; .dep), DEP, SHP"; args[6] = "false"; dfOut = new DialogFile(communicator); dfOut.setArgs(args); dfOut.addPropertyChangeListener("value", this); dfOut.setTextFieldActionListener(new ActionListener() { @Override public void actionPerformed(ActionEvent evt) { //showFeedback("Hello"); } }); mainBox.add(dfOut); mainBox.add(Box.createVerticalStrut(5)); ll2utmButton = new JRadioButton("Geographic (Lat/Long) to UTM"); //LL2UTMButton.setMnemonic(KeyEvent.VK_R); ll2utmButton.setActionCommand("ll2utm"); ll2utmButton.setSelected(true); utm2llButton = new JRadioButton("UTM to Geographic (Lat/Long)"); //utm2llButton.setMnemonic(KeyEvent.VK_P); utm2llButton.setActionCommand("utm2ll"); //Group the radio buttons. ButtonGroup group = new ButtonGroup(); group.add(ll2utmButton); group.add(utm2llButton); //Register a listener for the radio buttons. ll2utmButton.addActionListener(new ActionListener() { @Override public void actionPerformed(ActionEvent e) { projectionDirection = "ll2utm"; } }); utm2llButton.addActionListener(new ActionListener() { @Override public void actionPerformed(ActionEvent e) { projectionDirection = "utm2ll"; } }); Box box1 = Box.createHorizontalBox(); box1.add(ll2utmButton); box1.add(utm2llButton); mainBox.add(box1); mainBox.add(Box.createVerticalStrut(5)); // ellipsoid combobox String[] ellipsoids = new String[Ellipsoid.values().length]; int defaultEllipsoid = 0; int i = 0; for (Ellipsoid ellipse : Ellipsoid.values()) { ellipsoids[i] = ellipse.ellipsoidName(); if (ellipsoids[i].toLowerCase().replace(" ", "").equals("wgs84")) { defaultEllipsoid = i; } i++; } // ellipsoid ellipsoidChooser = new ComboBoxProperty( bundle.getString("Ellipsoid") + ":", ellipsoids, defaultEllipsoid); ellipsoidChooser.setName("ellipsoidChooser"); ItemListener il = new ItemListener() { @Override public void itemStateChanged(ItemEvent e) { if (e.getStateChange() == ItemEvent.SELECTED) { Object item = e.getItem(); ellipsoid = Ellipsoid.getEllipsoidByName(item.toString()); } } }; ellipsoidChooser.setParentListener(il); ellipsoidChooser.setBackColour(this.getBackground()); mainBox.add(ellipsoidChooser); // N or S northButton = new JRadioButton("North"); //LL2UTMButton.setMnemonic(KeyEvent.VK_R); northButton.setActionCommand("north"); northButton.setSelected(true); southButton = new JRadioButton("South"); //utm2llButton.setMnemonic(KeyEvent.VK_P); southButton.setActionCommand("south"); //Group the radio buttons. ButtonGroup group2 = new ButtonGroup(); group2.add(northButton); group2.add(southButton); //Register a listener for the radio buttons. //ll2utmButton.addActionListener(this); //utm2llButton.addActionListener(this); // Box box2 = Box.createHorizontalBox(); // box2.add(northButton); // box2.add(southButton); // //mainBox.add(box2); // UTM zone String[] zones = new String[60]; for (int a = 0; a < 60; a++) { zones[a] = String.valueOf(a + 1); } zoneChooser = new ComboBoxProperty( "Zone:", zones, 0); zoneChooser.setName("zoneChooser"); ItemListener il3 = new ItemListener() { @Override public void itemStateChanged(ItemEvent e) { if (e.getStateChange() == ItemEvent.SELECTED) { Object item = e.getItem(); utmZoneNumber = Integer.parseInt(item.toString()); } } }; zoneChooser.setParentListener(il3); zoneChooser.setBackColour(this.getBackground()); Box box2 = Box.createHorizontalBox(); box2.add(zoneChooser); box2.add(northButton); box2.add(southButton); mainBox.add(box2); Box box3 = Box.createHorizontalBox(); spansUTMZones.setForeground(Color.red); spansUTMZones.setVisible(false); box3.add(Box.createHorizontalStrut(10)); box3.add(spansUTMZones); box3.add(Box.createHorizontalGlue()); mainBox.add(box3); mainBox.add(Box.createVerticalStrut(5)); // interpolation method String[] interpolationMethods = {"Nearest Neighbour", "Bilinear"}; interpolationChooser = new ComboBoxProperty( "Interpolation Method:", interpolationMethods, 0); interpolationChooser.setName("interpolationChooser"); interpolationChooser.setVisible(false); ItemListener il2 = new ItemListener() { @Override public void itemStateChanged(ItemEvent e) { if (e.getStateChange() == ItemEvent.SELECTED) { Object item = e.getItem(); interpolationMethod = item.toString(); } } }; interpolationChooser.setParentListener(il2); interpolationChooser.setBackColour(this.getBackground()); mainBox.add(interpolationChooser); mainBox.add(Box.createVerticalStrut(15)); Box btnBox = Box.createHorizontalBox(); btnBox.add(Box.createHorizontalGlue()); JButton ok = new JButton(bundle.getString("OK")); ok.setActionCommand("ok"); ok.addActionListener(this); btnBox.add(ok); btnBox.add(Box.createHorizontalStrut(10)); JButton close = new JButton(bundle.getString("Close")); close.addActionListener(new ActionListener() { @Override public void actionPerformed(ActionEvent e) { closeParentDialog(); } }); btnBox.add(close); btnBox.add(Box.createHorizontalStrut(10)); cancel = new JButton("Cancel"); cancel.addActionListener(new ActionListener() { @Override public void actionPerformed(ActionEvent e) { thread.interrupt(); } }); cancel.setEnabled(false); btnBox.add(cancel); btnBox.add(Box.createHorizontalGlue()); mainBox.add(Box.createVerticalGlue()); mainBox.add(btnBox); mainBox.add(Box.createVerticalStrut(15)); this.add(mainBox); this.setPreferredSize(new Dimension(500, 350)); } private void closeParentDialog() { try { this.getTopLevelAncestor().setVisible(false); } catch (Exception e) { System.out.println(e.toString()); } } private void customizeUI() { try { if (inputFile == null \|\| inputFile.isEmpty()) { return; } if (inputFileIsRaster) { interpolationChooser.setVisible(true); WhiteboxRasterInfo input = new WhiteboxRasterInfo(inputFile); east = input.getEast(); west = input.getWest(); south = input.getSouth(); north = input.getNorth(); boolean isLatLong = true; if (east < -180 \|\| east > 180) { isLatLong = false; } if (west < -180 \|\| west > 180) { isLatLong = false; } if (north > 90 \|\| north < -90) { isLatLong = false; } if (south > 90 \|\| south < -90) { isLatLong = false; } if (isLatLong) { ll2utmButton.setSelected(true); projectionDirection = "ll2utm"; // select the appropriate zone number ellipsoid = Ellipsoid.getEllipsoidByName(ellipsoidChooser.getValue()); LL2UTM ll2utm = new LL2UTM(ellipsoid); ll2utm.convertGeographicCoordinates(north, west); int zone = ll2utm.getZone(); boolean spansZones = false; ll2utm.convertGeographicCoordinates(north, east); if (ll2utm.getZone() != zone) { spansZones = true; } ll2utm.convertGeographicCoordinates(south, west); if (ll2utm.getZone() != zone) { spansZones = true; } ll2utm.convertGeographicCoordinates(south, east); if (ll2utm.getZone() != zone) { spansZones = true; } if (spansZones) { spansUTMZones.setVisible(true); // use the zone of the centroid ll2utm.convertGeographicCoordinates((south + north) / 2.0, (west + east) / 2.0); zone = ll2utm.getZone(); } else { spansUTMZones.setVisible(false); } zoneChooser.setDefaultItem(zone - 1); utmZoneNumber = zone; zoneChooser.revalidate(); String hemi = ll2utm.getHemisphere(); if (hemi.toLowerCase().equals("s")) { southButton.setSelected(true); } else { northButton.setSelected(true); } } else { utm2llButton.setSelected(true); projectionDirection = "utm2ll"; } } else { interpolationChooser.setVisible(false); ShapeFile input = new ShapeFile(inputFile); east = input.getxMax(); west = input.getxMin(); south = input.getyMin(); north = input.getyMax(); boolean isLatLong = true; if (east < -180 \|\| east > 180) { isLatLong = false; } if (west < -180 \|\| west > 180) { isLatLong = false; } if (north > 90 \|\| north < -90) { isLatLong = false; } if (south > 90 \|\| south < -90) { isLatLong = false; } if (isLatLong) { ll2utmButton.setSelected(true); projectionDirection = "ll2utm"; // select the appropriate zone number ellipsoid = Ellipsoid.getEllipsoidByName(ellipsoidChooser.getValue()); LL2UTM ll2utm = new LL2UTM(ellipsoid); ll2utm.convertGeographicCoordinates(north, west); int zone = ll2utm.getZone(); boolean spansZones = false; ll2utm.convertGeographicCoordinates(north, east); if (ll2utm.getZone() != zone) { spansZones = true; } ll2utm.convertGeographicCoordinates(south, west); if (ll2utm.getZone() != zone) { spansZones = true; } ll2utm.convertGeographicCoordinates(south, east); if (ll2utm.getZone() != zone) { spansZones = true; } if (spansZones) { spansUTMZones.setVisible(true); // use the zone of the centroid ll2utm.convertGeographicCoordinates((south + north) / 2.0, (west + east) / 2.0); zone = ll2utm.getZone(); } else { spansUTMZones.setVisible(false); } zoneChooser.setDefaultItem(zone - 1); zoneChooser.revalidate(); String hemi = ll2utm.getHemisphere(); if (hemi.toLowerCase().equals("s")) { southButton.setSelected(true); } else { northButton.setSelected(true); } } else { utm2llButton.setSelected(true); projectionDirection = "utm2ll"; } } } catch (OutOfMemoryError oe) { myHost.showFeedback("An out-of-memory error has occurred during operation."); } catch (Exception e) { myHost.showFeedback("An error has occurred during operation. See log file for details."); myHost.logException("Error in " + getDescriptiveName(), e); } } private boolean inputFileIsRaster = true; @Override public void propertyChange(PropertyChangeEvent evt) { Object source = evt.getSource(); if (!evt.getPropertyName().equals("value")) { return; } if (source == dfIn) { if (dfIn.getValue() != null) { File file = new File(dfIn.getValue()); if (file.exists()) { if (file.toString().toLowerCase().endsWith(".dep")) { inputFileIsRaster = true; inputFile = file.toString(); customizeUI(); } else if (file.toString().toLowerCase().endsWith(".shp")) { inputFileIsRaster = false; inputFile = file.toString(); customizeUI(); } else { // somehow neither a raster nor vector file has been selected. return; } } } } } @Override public void notifyOfThreadComplete(Runnable thread) { cancel.setEnabled(false); } @Override public void notifyOfReturn(String ret) { } @Override public void notifyOfProgress(int progressVal) { host.updateProgress(progressVal); } @Override public void passOnThreadException(Exception e) { throw new UnsupportedOperationException("Not supported yet."); //To change body of generated methods, choose Tools \| Templates. } @Override public int showFeedback(String feedback) { host.showFeedback(feedback); return 0; } @Override public void actionPerformed(ActionEvent e) { if (e.getActionCommand().equals("ok")) { CoordTransform ct = new CoordTransform(this, ellipsoid); String[] myArgs = new String[7]; myArgs[0] = inputFile; myArgs[1] = dfOut.getValue(); // output file myArgs[2] = String.valueOf(inputFileIsRaster); myArgs[3] = projectionDirection; myArgs[4] = String.valueOf(utmZoneNumber); //zoneChooser.getValue(); if (northButton.isSelected()) { myArgs[5] = "N"; } else { myArgs[5] = "S"; } myArgs[6] = interpolationMethod; ct.setArgs(myArgs); cancel.setEnabled(true); thread = new Thread(ct); thread.start(); } } public void cancelOperation() { if (thread.isAlive()) { thread.interrupt(); } } } class CoordTransform implements Runnable { private ThreadListener myListener = null; private String[] args; private Ellipsoid ellipsoid; CoordTransform(ThreadListener listener, Ellipsoid ellipsoid) { this.myListener = listener; this.ellipsoid = ellipsoid; } public void setArgs(String[] args) { this.args = args; } private boolean checkIfThreadIsInterrupted() { if (Thread.currentThread().isInterrupted()) { return true; } else { return false; } } private void cancelOp() { if (myListener != null) { myListener.notifyOfThreadComplete(this); updateProgress(0); //showFeedback("Operation cancelled!"); } } @Override public void run() { double north, south, east, west; double minEasting, maxEasting, minNorthing, maxNorthing; try { String inputFile = args[0]; String outputFile = args[1]; boolean inputFileIsRaster = Boolean.parseBoolean(args[2]); String projectionDirection = args[3]; int zone = Integer.parseInt(args[4]); String hemi = args[5]; String interpolationMethod = args[6]; int oldProgress = -1; int progress = 0; double easting, northing; // get the file names //String inputFile = dfIn.getValue(); if (inputFileIsRaster && outputFile.toLowerCase().endsWith(".shp")) { if (outputFile.endsWith(".shp")) { outputFile = outputFile.replace(".shp", ".dep"); } else if (outputFile.endsWith(".SHP")) { outputFile = outputFile.replace(".SHP", ".dep"); } } else if (!inputFileIsRaster && outputFile.toLowerCase().endsWith(".dep")) { if (outputFile.endsWith(".dep")) { outputFile = outputFile.replace(".dep", ".shp"); } else if (outputFile.endsWith(".DEP")) { outputFile = outputFile.replace(".DEP", ".shp"); } } if (inputFileIsRaster) { WhiteboxRaster input = new WhiteboxRaster(inputFile, "r"); int inputCols = input.getNumberColumns(); int inputRows = input.getNumberRows(); double noData = input.getNoDataValue(); east = input.getEast(); west = input.getWest(); south = input.getSouth(); north = input.getNorth(); if (projectionDirection.equals("ll2utm")) { LL2UTM ll2utm = new LL2UTM(ellipsoid); //zone = Integer.parseInt(zoneChooser.getValue()); ll2utm.setZone(zone); //String hemi; // if (northButton.isSelected()) { // hemi = "N"; // } else { // hemi = "S"; // } ll2utm.setHemisphere(hemi); ll2utm.lockZone(); minEasting = Double.POSITIVE_INFINITY; maxEasting = Double.NEGATIVE_INFINITY; minNorthing = Double.POSITIVE_INFINITY; maxNorthing = Double.NEGATIVE_INFINITY; //Calculate the Eastings and northings of each of the four corners and find the min and max ll2utm.convertGeographicCoordinates(north, west); easting = ll2utm.getEasting(); northing = ll2utm.getNorthing(); String utmZone = zone + hemi; if (easting < minEasting) { minEasting = easting; } if (northing < minNorthing) { minNorthing = northing; } if (easting > maxEasting) { maxEasting = easting; } if (northing > maxNorthing) { maxNorthing = northing; } ll2utm.convertGeographicCoordinates(north, east); easting = ll2utm.getEasting(); northing = ll2utm.getNorthing(); if (easting < minEasting) { minEasting = easting; } if (northing < minNorthing) { minNorthing = northing; } if (easting > maxEasting) { maxEasting = easting; } if (northing > maxNorthing) { maxNorthing = northing; } ll2utm.convertGeographicCoordinates(south, east); easting = ll2utm.getEasting(); northing = ll2utm.getNorthing(); if (easting < minEasting) { minEasting = easting; } if (northing < minNorthing) { minNorthing = northing; } if (easting > maxEasting) { maxEasting = easting; } if (northing > maxNorthing) { maxNorthing = northing; } ll2utm.convertGeographicCoordinates(south, west); easting = ll2utm.getEasting(); northing = ll2utm.getNorthing(); if (easting < minEasting) { minEasting = easting; } if (northing < minNorthing) { minNorthing = northing; } if (easting > maxEasting) { maxEasting = easting; } if (northing > maxNorthing) { maxNorthing = northing; } double xDist = maxEasting - minEasting; double yDist = maxNorthing - minNorthing; double xRes = xDist / inputCols; double yRes = yDist / inputRows; double avgRes = (xRes + yRes) / 2.0; int outputCols = (int) (xDist / avgRes); int outputRows = (int) (yDist / avgRes); WhiteboxRaster output = new WhiteboxRaster(outputFile, maxNorthing, minNorthing, maxEasting, minEasting, outputRows, outputCols, input.getDataScale(), input.getDataType(), noData, noData); output.setPreferredPalette(input.getPreferredPalette()); int inRow, inCol; UTM2LL utm2ll = new UTM2LL(ellipsoid, utmZone); double inLat, inLng; double outEasting, outNorthing; double z; if (interpolationMethod.toLowerCase().contains("nearest")) { // nearest neighbour for (int row = 0; row < outputRows; row++) { for (int col = 0; col < outputCols; col++) { outEasting = output.getXCoordinateFromColumn(col); outNorthing = output.getYCoordinateFromRow(row); utm2ll.convertUTMCoordinates(outEasting, outNorthing); inLat = utm2ll.getLatitude(); inLng = utm2ll.getLongitude(); inCol = input.getColumnFromXCoordinate(inLng); inRow = input.getRowFromYCoordinate(inLat); z = input.getValue(inRow, inCol); output.setValue(row, col, z); } progress = (int) (100f row / (outputRows - 1)); if (progress > oldProgress) { updateProgress(progress); oldProgress = progress; if (checkIfThreadIsInterrupted()) { cancelOp(); return; } } } } else { // bilinear double dX, dY; double srcRow, srcCol; double originRow, originCol; double rowN, colN; double sumOfDist; double[] shiftX = new double[]{0, 1, 0, 1}; double[] shiftY = new double[]{0, 0, 1, 1}; int numNeighbours = 4; double[][] neighbour = new double[numNeighbours][2]; int i; double inNSRange = Math.abs(north - south); double inEWRange = Math.abs(east - west); for (int row = 0; row < outputRows; row++) { for (int col = 0; col < outputCols; col++) { outEasting = output.getXCoordinateFromColumn(col); outNorthing = output.getYCoordinateFromRow(row); utm2ll.convertUTMCoordinates(outEasting, outNorthing); inLat = utm2ll.getLatitude(); inLng = utm2ll.getLongitude(); // what are the exact col and row of the image? srcRow = (north - inLat) / inNSRange * (inputRows - 0.5); srcCol = (inLng - west) / inEWRange * (inputCols - 0.5); originRow = Math.floor(srcRow); originCol = Math.floor(srcCol); sumOfDist = 0; for (i = 0; i < numNeighbours; i++) { rowN = originRow + shiftY[i]; colN = originCol + shiftX[i]; neighbour[i][0] = input.getValue((int) rowN, (int) colN); dY = rowN - srcRow; dX = colN - srcCol; if ((dX + dY) != 0 && neighbour[i][0] != noData) { neighbour[i][1] = 1 / (dX * dX + dY * dY); sumOfDist += neighbour[i][1]; } else if (neighbour[i][0] == noData) { neighbour[i][1] = 0; } else { // dist is zero neighbour[i][1] = 99999999; sumOfDist += neighbour[i][1]; } } if (sumOfDist > 0) { z = 0; for (i = 0; i < numNeighbours; i++) { z += neighbour[i][0] * neighbour[i][1] / sumOfDist; } } else { z = noData; } output.setValue(row, col, z); } progress = (int) (100f * row / (outputRows - 1)); if (progress > oldProgress) { updateProgress(progress); oldProgress = progress; if (checkIfThreadIsInterrupted()) { cancelOp(); return; } } } } output.addMetadataEntry("Created by the " + getDescriptiveName() + " tool."); output.addMetadataEntry("Created on " + new Date()); output.addMetadataEntry("UTM Zone: " + utmZone); output.close(); } else { // utm2ll // String hemi; // if (northButton.isSelected()) { // hemi = "N"; // } else { // hemi = "S"; // } String utmZone = zone + hemi; UTM2LL utm2ll = new UTM2LL(ellipsoid, utmZone); minEasting = Double.POSITIVE_INFINITY; maxEasting = Double.NEGATIVE_INFINITY; minNorthing = Double.POSITIVE_INFINITY; maxNorthing = Double.NEGATIVE_INFINITY; //Calculate the Eastings and northings of each of the four corners and find the min and max utm2ll.convertUTMCoordinates(west, north); easting = utm2ll.getLongitude(); northing = utm2ll.getLatitude(); if (easting < minEasting) { minEasting = easting; } if (northing < minNorthing) { minNorthing = northing; } if (easting > maxEasting) { maxEasting = easting; } if (northing > maxNorthing) { maxNorthing = northing; } utm2ll.convertUTMCoordinates(east, north); easting = utm2ll.getLongitude(); northing = utm2ll.getLatitude(); if (easting < minEasting) { minEasting = easting; } if (northing < minNorthing) { minNorthing = northing; } if (easting > maxEasting) { maxEasting = easting; } if (northing > maxNorthing) { maxNorthing = northing; } utm2ll.convertUTMCoordinates(east, south); easting = utm2ll.getLongitude(); northing = utm2ll.getLatitude(); if (easting < minEasting) { minEasting = easting; } if (northing < minNorthing) { minNorthing = northing; } if (easting > maxEasting) { maxEasting = easting; } if (northing > maxNorthing) { maxNorthing = northing; } utm2ll.convertUTMCoordinates(west, south); easting = utm2ll.getLongitude(); northing = utm2ll.getLatitude(); if (easting < minEasting) { minEasting = easting; } if (northing < minNorthing) { minNorthing = northing; } if (easting > maxEasting) { maxEasting = easting; } if (northing > maxNorthing) { maxNorthing = northing; } double xDist = maxEasting - minEasting; double yDist = maxNorthing - minNorthing; double xRes = xDist / inputCols; double yRes = yDist / inputRows; double avgRes = (xRes + yRes) / 2.0; int outputCols = (int) (xDist / avgRes); int outputRows = (int) (yDist / avgRes); WhiteboxRaster output = new WhiteboxRaster(outputFile, maxNorthing, minNorthing, maxEasting, minEasting, outputRows, outputCols, input.getDataScale(), input.getDataType(), noData, noData); output.setPreferredPalette(input.getPreferredPalette()); int inRow, inCol; LL2UTM ll2utm = new LL2UTM(ellipsoid); ll2utm.setZone(zone); ll2utm.setHemisphere(hemi); ll2utm.lockZone(); double inNorthing, inEasting; double outLng, outLat; double z; if (interpolationMethod.toLowerCase().contains("nearest")) { // nearest neighbour for (int row = 0; row < outputRows; row++) { for (int col = 0; col < outputCols; col++) { outLng = output.getXCoordinateFromColumn(col); outLat = output.getYCoordinateFromRow(row); ll2utm.convertGeographicCoordinates(outLat, outLng); inNorthing = ll2utm.getNorthing(); inEasting = ll2utm.getEasting(); inCol = input.getColumnFromXCoordinate(inEasting); inRow = input.getRowFromYCoordinate(inNorthing); z = input.getValue(inRow, inCol); output.setValue(row, col, z); } progress = (int) (100f * row / (outputRows - 1)); if (progress > oldProgress) { updateProgress(progress); oldProgress = progress; if (checkIfThreadIsInterrupted()) { cancelOp(); return; } } } } else { // bilinear if (input.getDataScale() == WhiteboxRaster.DataScale.RGB) { showFeedback("Bilinear interpolation should not be used " + "for transforming RGB type rasters. Use " + "nearest neighbour interpolation instead"); return; } double dX, dY; double srcRow, srcCol; double originRow, originCol; double rowN, colN; double sumOfDist; double[] shiftX = new double[]{0, 1, 0, 1}; double[] shiftY = new double[]{0, 0, 1, 1}; int numNeighbours = 4; double[][] neighbour = new double[numNeighbours][2]; int i; double inNSRange = Math.abs(north - south); double inEWRange = Math.abs(east - west); for (int row = 0; row < outputRows; row++) { for (int col = 0; col < outputCols; col++) { outLng = output.getXCoordinateFromColumn(col); outLat = output.getYCoordinateFromRow(row); ll2utm.convertGeographicCoordinates(outLat, outLng); inNorthing = ll2utm.getNorthing(); inEasting = ll2utm.getEasting(); // what are the exact col and row of the image? srcRow = (north - inNorthing) / inNSRange * (inputRows - 0.5); srcCol = (inEasting - west) / inEWRange * (inputCols - 0.5); originRow = Math.floor(srcRow); originCol = Math.floor(srcCol); sumOfDist = 0; for (i = 0; i < numNeighbours; i++) { rowN = originRow + shiftY[i]; colN = originCol + shiftX[i]; neighbour[i][0] = input.getValue((int) rowN, (int) colN); dY = rowN - srcRow; dX = colN - srcCol; if ((dX + dY) != 0 && neighbour[i][0] != noData) { neighbour[i][1] = 1 / (dX * dX + dY * dY); sumOfDist += neighbour[i][1]; } else if (neighbour[i][0] == noData) { neighbour[i][1] = 0; } else { // dist is zero neighbour[i][1] = 99999999; sumOfDist += neighbour[i][1]; } } if (sumOfDist > 0) { z = 0; for (i = 0; i < numNeighbours; i++) { z += neighbour[i][0] * neighbour[i][1] / sumOfDist; } } else { z = noData; } output.setValue(row, col, z); } progress = (int) (100f * row / (outputRows - 1)); if (progress > oldProgress) { updateProgress(progress); oldProgress = progress; if (checkIfThreadIsInterrupted()) { cancelOp(); return; } } } } output.addMetadataEntry("Created by the " + getDescriptiveName() + " tool."); output.addMetadataEntry("Created on " + new Date()); output.addMetadataEntry("UTM Zone: " + utmZone); output.close(); } } else { // vector input int numFeatures, n, oneHundredthTotal, i; double x, y, z, m; double[] zArray; double[] mArray; double[][] outPoints; int[] parts; if (projectionDirection.equals("ll2utm")) { ShapeFile input = new ShapeFile(inputFile); east = input.getxMax(); west = input.getxMin(); south = input.getyMin(); north = input.getyMax(); LL2UTM ll2utm = new LL2UTM(ellipsoid); // zone = Integer.parseInt(zoneChooser.getValue()); ll2utm.setZone(zone); // String hemi; // if (northButton.isSelected()) { // hemi = "N"; // } else { // hemi = "S"; // } ll2utm.setHemisphere(hemi); ll2utm.lockZone(); // set up the output files of the shapefile and the dbf ShapeType shapeType = input.getShapeType(); ShapeFile output = new ShapeFile(outputFile, shapeType); FileUtilities.copyFile(new File(input.getDatabaseFile()), new File(output.getDatabaseFile())); numFeatures = input.getNumberOfRecords(); oneHundredthTotal = numFeatures / 100; n = 0; progress = 0; double[][] recordPoints; for (ShapeFileRecord record : input.records) { switch (shapeType) { case POINT: whitebox.geospatialfiles.shapefile.Point recPoint = (whitebox.geospatialfiles.shapefile.Point) (record.getGeometry()); recordPoints = recPoint.getPoints(); x = recordPoints[0][0]; y = recordPoints[0][1]; ll2utm.convertGeographicCoordinates(y, x); whitebox.geospatialfiles.shapefile.Point outRecPoint = new whitebox.geospatialfiles.shapefile.Point( ll2utm.getEasting(), ll2utm.getNorthing()); output.addRecord(outRecPoint); break; case POINTZ: PointZ recPointZ = (PointZ) (record.getGeometry()); recordPoints = recPointZ.getPoints(); x = recordPoints[0][0]; y = recordPoints[0][1]; z = recPointZ.getZ(); m = recPointZ.getM(); ll2utm.convertGeographicCoordinates(y, x); PointZ outRecPointZ = new PointZ( ll2utm.getEasting(), ll2utm.getNorthing(), z, m); output.addRecord(outRecPointZ); break; case POINTM: PointM recPointM = (PointM) (record.getGeometry()); recordPoints = recPointM.getPoints(); x = recordPoints[0][0]; y = recordPoints[0][1]; m = recPointM.getM(); ll2utm.convertGeographicCoordinates(y, x); PointM outRecPointM = new PointM( ll2utm.getEasting(), ll2utm.getNorthing(), m); output.addRecord(outRecPointM); break; case MULTIPOINT: MultiPoint mp = (MultiPoint) (record.getGeometry()); recordPoints = mp.getPoints(); outPoints = new double[recordPoints.length][2]; for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; ll2utm.convertGeographicCoordinates(y, x); outPoints[i][0] = ll2utm.getEasting(); outPoints[i][1] = ll2utm.getNorthing(); } MultiPoint outMP = new MultiPoint( outPoints); output.addRecord(outMP); break; case MULTIPOINTZ: MultiPointZ mpZ = (MultiPointZ) (record.getGeometry()); recordPoints = mpZ.getPoints(); outPoints = new double[recordPoints.length][2]; zArray = mpZ.getzArray(); mArray = mpZ.getmArray(); for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; ll2utm.convertGeographicCoordinates(y, x); outPoints[i][0] = ll2utm.getEasting(); outPoints[i][1] = ll2utm.getNorthing(); } MultiPointZ outMPZ = new MultiPointZ( outPoints, zArray, mArray); output.addRecord(outMPZ); break; case MULTIPOINTM: MultiPointM mpM = (MultiPointM) (record.getGeometry()); recordPoints = mpM.getPoints(); outPoints = new double[recordPoints.length][2]; mArray = mpM.getmArray(); for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; ll2utm.convertGeographicCoordinates(y, x); outPoints[i][0] = ll2utm.getEasting(); outPoints[i][1] = ll2utm.getNorthing(); } MultiPointM outMPM = new MultiPointM( outPoints, mArray); output.addRecord(outMPM); break; case POLYLINE: PolyLine pl = (PolyLine) (record.getGeometry()); recordPoints = pl.getPoints(); outPoints = new double[recordPoints.length][2]; parts = pl.getParts(); for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; ll2utm.convertGeographicCoordinates(y, x); outPoints[i][0] = ll2utm.getEasting(); outPoints[i][1] = ll2utm.getNorthing(); } PolyLine outPL = new PolyLine(parts, outPoints); output.addRecord(outPL); break; case POLYLINEZ: PolyLineZ plZ = (PolyLineZ) (record.getGeometry()); recordPoints = plZ.getPoints(); outPoints = new double[recordPoints.length][2]; parts = plZ.getParts(); zArray = plZ.getzArray(); mArray = plZ.getmArray(); for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; ll2utm.convertGeographicCoordinates(y, x); outPoints[i][0] = ll2utm.getEasting(); outPoints[i][1] = ll2utm.getNorthing(); } PolyLineZ outPLZ = new PolyLineZ(parts, outPoints, zArray, mArray); output.addRecord(outPLZ); break; case POLYLINEM: PolyLineM plM = (PolyLineM) (record.getGeometry()); recordPoints = plM.getPoints(); outPoints = new double[recordPoints.length][2]; parts = plM.getParts(); mArray = plM.getmArray(); for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; ll2utm.convertGeographicCoordinates(y, x); outPoints[i][0] = ll2utm.getEasting(); outPoints[i][1] = ll2utm.getNorthing(); } PolyLineM outPLM = new PolyLineM(parts, outPoints, mArray); output.addRecord(outPLM); break; case POLYGON: Polygon pg = (Polygon) (record.getGeometry()); recordPoints = pg.getPoints(); outPoints = new double[recordPoints.length][2]; parts = pg.getParts(); for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; ll2utm.convertGeographicCoordinates(y, x); outPoints[i][0] = ll2utm.getEasting(); outPoints[i][1] = ll2utm.getNorthing(); } Polygon outPG = new Polygon(parts, outPoints); output.addRecord(outPG); break; case POLYGONZ: PolygonZ pgZ = (PolygonZ) (record.getGeometry()); recordPoints = pgZ.getPoints(); outPoints = new double[recordPoints.length][2]; parts = pgZ.getParts(); zArray = pgZ.getzArray(); mArray = pgZ.getmArray(); for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; ll2utm.convertGeographicCoordinates(y, x); outPoints[i][0] = ll2utm.getEasting(); outPoints[i][1] = ll2utm.getNorthing(); } PolygonZ outPGZ = new PolygonZ(parts, outPoints, zArray, mArray); output.addRecord(outPGZ); break; case POLYGONM: PolygonM pgM = (PolygonM) (record.getGeometry()); recordPoints = pgM.getPoints(); outPoints = new double[recordPoints.length][2]; parts = pgM.getParts(); mArray = pgM.getmArray(); for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; ll2utm.convertGeographicCoordinates(y, x); outPoints[i][0] = ll2utm.getEasting(); outPoints[i][1] = ll2utm.getNorthing(); } PolygonM outPGM = new PolygonM(parts, outPoints, mArray); output.addRecord(outPGM); break; default: break; } n++; if (n >= oneHundredthTotal) { n = 0; if (checkIfThreadIsInterrupted()) { cancelOp(); return; } progress++; updateProgress(progress); } } output.write(); } else { // utm2ll ShapeFile input = new ShapeFile(inputFile); east = input.getxMax(); west = input.getxMin(); south = input.getyMin(); north = input.getyMax(); // String hemi; // if (northButton.isSelected()) { // hemi = "N"; // } else { // hemi = "S"; // } String utmZone = zone + hemi; UTM2LL utm2ll = new UTM2LL(ellipsoid, utmZone); // set up the output files of the shapefile and the dbf ShapeType shapeType = input.getShapeType(); ShapeFile output = new ShapeFile(outputFile, shapeType); FileUtilities.copyFile(new File(input.getDatabaseFile()), new File(output.getDatabaseFile())); numFeatures = input.getNumberOfRecords(); oneHundredthTotal = numFeatures / 100; n = 0; progress = 0; double[][] recordPoints; for (ShapeFileRecord record : input.records) { switch (shapeType) { case POINT: whitebox.geospatialfiles.shapefile.Point recPoint = (whitebox.geospatialfiles.shapefile.Point) (record.getGeometry()); recordPoints = recPoint.getPoints(); x = recordPoints[0][0]; y = recordPoints[0][1]; utm2ll.convertUTMCoordinates(x, y); whitebox.geospatialfiles.shapefile.Point outRecPoint = new whitebox.geospatialfiles.shapefile.Point( utm2ll.getLongitude(), utm2ll.getLatitude()); output.addRecord(outRecPoint); break; case POINTZ: PointZ recPointZ = (PointZ) (record.getGeometry()); recordPoints = recPointZ.getPoints(); x = recordPoints[0][0]; y = recordPoints[0][1]; z = recPointZ.getZ(); m = recPointZ.getM(); utm2ll.convertUTMCoordinates(x, y); PointZ outRecPointZ = new PointZ( utm2ll.getLongitude(), utm2ll.getLatitude(), z, m); output.addRecord(outRecPointZ); break; case POINTM: PointM recPointM = (PointM) (record.getGeometry()); recordPoints = recPointM.getPoints(); x = recordPoints[0][0]; y = recordPoints[0][1]; m = recPointM.getM(); utm2ll.convertUTMCoordinates(x, y); PointM outRecPointM = new PointM( utm2ll.getLongitude(), utm2ll.getLatitude(), m); output.addRecord(outRecPointM); break; case MULTIPOINT: MultiPoint mp = (MultiPoint) (record.getGeometry()); recordPoints = mp.getPoints(); outPoints = new double[recordPoints.length][2]; for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; utm2ll.convertUTMCoordinates(x, y); outPoints[i][0] = utm2ll.getLongitude(); outPoints[i][1] = utm2ll.getLatitude(); } MultiPoint outMP = new MultiPoint( outPoints); output.addRecord(outMP); break; case MULTIPOINTZ: MultiPointZ mpZ = (MultiPointZ) (record.getGeometry()); recordPoints = mpZ.getPoints(); outPoints = new double[recordPoints.length][2]; zArray = mpZ.getzArray(); mArray = mpZ.getmArray(); for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; utm2ll.convertUTMCoordinates(x, y); outPoints[i][0] = utm2ll.getLongitude(); outPoints[i][1] = utm2ll.getLatitude(); } MultiPointZ outMPZ = new MultiPointZ( outPoints, zArray, mArray); output.addRecord(outMPZ); break; case MULTIPOINTM: MultiPointM mpM = (MultiPointM) (record.getGeometry()); recordPoints = mpM.getPoints(); outPoints = new double[recordPoints.length][2]; mArray = mpM.getmArray(); for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; utm2ll.convertUTMCoordinates(x, y); outPoints[i][0] = utm2ll.getLongitude(); outPoints[i][1] = utm2ll.getLatitude(); } MultiPointM outMPM = new MultiPointM( outPoints, mArray); output.addRecord(outMPM); break; case POLYLINE: PolyLine pl = (PolyLine) (record.getGeometry()); recordPoints = pl.getPoints(); outPoints = new double[recordPoints.length][2]; parts = pl.getParts(); for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; utm2ll.convertUTMCoordinates(x, y); outPoints[i][0] = utm2ll.getLongitude(); outPoints[i][1] = utm2ll.getLatitude(); } PolyLine outPL = new PolyLine(parts, outPoints); output.addRecord(outPL); break; case POLYLINEZ: PolyLineZ plZ = (PolyLineZ) (record.getGeometry()); recordPoints = plZ.getPoints(); outPoints = new double[recordPoints.length][2]; parts = plZ.getParts(); zArray = plZ.getzArray(); mArray = plZ.getmArray(); for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; utm2ll.convertUTMCoordinates(x, y); outPoints[i][0] = utm2ll.getLongitude(); outPoints[i][1] = utm2ll.getLatitude(); } PolyLineZ outPLZ = new PolyLineZ(parts, outPoints, zArray, mArray); output.addRecord(outPLZ); break; case POLYLINEM: PolyLineM plM = (PolyLineM) (record.getGeometry()); recordPoints = plM.getPoints(); outPoints = new double[recordPoints.length][2]; parts = plM.getParts(); mArray = plM.getmArray(); for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; utm2ll.convertUTMCoordinates(x, y); outPoints[i][0] = utm2ll.getLongitude(); outPoints[i][1] = utm2ll.getLatitude(); } PolyLineM outPLM = new PolyLineM(parts, outPoints, mArray); output.addRecord(outPLM); break; case POLYGON: Polygon pg = (Polygon) (record.getGeometry()); recordPoints = pg.getPoints(); outPoints = new double[recordPoints.length][2]; parts = pg.getParts(); for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; utm2ll.convertUTMCoordinates(x, y); outPoints[i][0] = utm2ll.getLongitude(); outPoints[i][1] = utm2ll.getLatitude(); } Polygon outPG = new Polygon(parts, outPoints); output.addRecord(outPG); break; case POLYGONZ: PolygonZ pgZ = (PolygonZ) (record.getGeometry()); recordPoints = pgZ.getPoints(); outPoints = new double[recordPoints.length][2]; parts = pgZ.getParts(); zArray = pgZ.getzArray(); mArray = pgZ.getmArray(); for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; utm2ll.convertUTMCoordinates(x, y); outPoints[i][0] = utm2ll.getLongitude(); outPoints[i][1] = utm2ll.getLatitude(); } PolygonZ outPGZ = new PolygonZ(parts, outPoints, zArray, mArray); output.addRecord(outPGZ); break; case POLYGONM: PolygonM pgM = (PolygonM) (record.getGeometry()); recordPoints = pgM.getPoints(); outPoints = new double[recordPoints.length][2]; parts = pgM.getParts(); mArray = pgM.getmArray(); for (i = 0; i < recordPoints.length; i++) { x = recordPoints[i][0]; y = recordPoints[i][1]; utm2ll.convertUTMCoordinates(x, y); outPoints[i][0] = utm2ll.getLongitude(); outPoints[i][1] = utm2ll.getLatitude(); } PolygonM outPGM = new PolygonM(parts, outPoints, mArray); output.addRecord(outPGM); break; default: break; } n++; if (n >= oneHundredthTotal) { n = 0; if (checkIfThreadIsInterrupted()) { cancelOp(); return; } progress++; updateProgress(progress); } } output.write(); } } updateProgress(0); myListener.notifyOfThreadComplete(this); showFeedback("Operation complete!"); } catch (Exception e) { myHost.showFeedback("An error has occurred during operation. See log file for details."); myHost.logException("Error in " + getDescriptiveName(), e); } finally { //amIActive = false; } } public void updateProgress(int progress) { if (myListener != null) { myListener.notifyOfProgress(progress); } } public void showFeedback(String message) { if (myListener != null) { myListener.showFeedback(message); } } } // public static void main(String[] args) { // CoordinateSystemTransformation cst = new CoordinateSystemTransformation(); // cst.testLaunch(); // // } private void testLaunch() { JFrame frame = new JFrame(); frame.add(new CoordinateTransformDialog(myHost)); frame.setDefaultCloseOperation(JFrame.DISPOSE_ON_CLOSE); frame.pack(); frame.setLocationRelativeTo(null); frame.setVisible(true); } }
North Korea’s Fissile Material Production: How to Know It’s All Gone Before the Hanoi Summit, President Trump suggested in remarks that he was in no rush for denuclearization as long as North Korea wasn’t testing missiles or nuclear weapons. It’s a good thing, too, since denuclearization didn’t happen at the Hanoi Summit. Did Trump simply seek to dampen expectations for the summit ahead of time? Or did this reveal a superficial understanding of what’s important for actual denuclearization? In any event, the all-or-nothing position Trump favored over a step-by-step denuclearization process made the best the enemy of the good by squandering an opportunity to begin the process of capping and eventually eliminating North Korea’s fissile material production. The Importance of Ending Fissile Material Production As nuclear weapons experts appreciate, testing is one of the last steps in a complex industrial program to build bombs and their delivery systems. And once testing has proven design concepts, its value diminishes. To limit North Korea’s true nuclear weapons capacity, there has to be a verifiable end to its fissile material production—the weapons-grade enriched uranium and plutonium whose atoms split apart in the process of fission, releasing the tremendous amounts of energy in nuclear weapons. Without monitoring the end of production of highly enriched uranium (HEU) or plutonium, it’s impossible to irreversibly eliminate North Korea’s current arsenal. Arms control and disarmament experts have long sought a global fissile material production cutoff treaty precisely for this reason—it is a way to cap the world’s stockpile of weapons-grade material on the path towards disarmament. Pyongyang, if media reports are correct, was ready to offer the shutdown of the Yongbyon Nuclear Scientific Research Center, home to its known fissile material production. Yongbyon hosts the 5 MWe production reactor that transmutates natural uranium into plutonium; a reprocessing plant that separates plutonium from uranium and radioactive waste; at least one centrifuge uranium enrichment facility; a fuel fabrication facility; a spent fuel storage facility; a small research reactor (IRT-2000-type pool reactor) for producing medical radioisotopes that uses 80 percent highly enriched uranium fuel; and, an experimental light water reactor (ELWR) under construction, as North Koreans tell us, to produce electricity. North Korea likely also has facilities for transforming weapons-grade material into weapons-ready shapes and forms. Metal conversion, casting and machining all precede assembly into warheads. It is not clear where those facilities are, but it’s a good bet they are somewhere on or near the Yongbyon site. Even in a well-crafted denuclearization process, North Korea might choose to simply destroy such facilities rather than submit them to verification. For the purposes of verifying that North Korea is no longer producing fissile material for weapons, those facilities are less important because they are only relevant to the weapons fabrication process. Who knows what Pyongyang had in mind when it offered to shut down Yongbyon. The best case would have been a process in which North Korea declared all its facilities and provided their records, put all of its inventory under international safeguards, shipped it out of the country, or processed it so it could not be used for weapons, and then dismantled the site altogether. These tasks would take years to complete properly. North Korea probably had something less comprehensive in mind. To be sure, even a complete dismantlement of everything at Yongbyon would not have been the end of the story since there are almost certainly other facilities connected to fissile material production that are hidden. Some experts contend there is a second uranium enrichment plant at Kangsong. Any agreement worth signing would need a mechanism to provide confidence that North Korea’s stockpile was not growing anywhere in the country. Good, Better, Best The “go for broke” strategy employed by the Trump administration is sacrificing the good for the best. Whatever happens to negotiations now, North Korea’s fissile material production is the key to the size of its arsenal and well worth targeted efforts to cap and eventually eliminate. What are some of the steps worth taking? 1. Moratorium on fissile material production A declaration of no more fissile material production hardly seems worthwhile, but Russia, the US, the UK and France all declared moratoria on producing fissile material for nuclear weapons two decades ago and have not resumed production. A simple declaration by North Korea would be the quickest, easiest and cheapest action to take. This would be a confidence-building measure by North Korea that would bring it into line with established nuclear weapon state behaviors, with the exception of China. A multilateral approach to North Korea with all nuclear weapon states reaffirming their commitments and China joining in could be a “win” not just on the Korean Peninsula but also globally. At a time when all the nuclear weapon states have modernization programs and there is a potential risk of a new arms race between the US and Russia, it wouldn’t be a bad idea for these countries to reaffirm their commitments to cap fissile material production. The International Atomic Energy Agency (IAEA), which has been watching North Korea from afar since its inspectors were last kicked out ten years ago, recently confirmed that the 5 MWe reactor and the reprocessing plant have not been operating. Satellite imagery and other techniques to monitor environmental signals from operations can help provide confidence that this is the case. Should the North begin to operate its experimental light water reactor, the pattern of operations can help establish whether it is operating to produce weapons-grade plutonium or electricity. Of course, Pyongyang could provide additional confidence by asking the IAEA to apply safeguards to the civilian reactor. It would need to rejoin the IAEA and pay its dues, but then potentially receive technical assistance to ensure the reactor was safe, secure and optimized for efficient electricity generation. The country might also consider, for similar reasons, inviting the IAEA to apply safeguards to its IRT research reactor. A moratorium on uranium enrichment would be impossible to monitor remotely without North Korea’s cooperation. Ironically, it might prefer providing assurances of no enrichment at all rather than attempting to show it is not producing highly enriched uranium because of the intrusiveness of measures in the latter case (think “Iran”). For example, North Korea could allow verification of the absence of key equipment (e.g., feed and withdrawal units) or inputs (uranium hexafluoride). There would still be uncertainty about undeclared enrichment sites, which would need to be addressed. 2. Monitored production or closure North Korea’s permission to allow monitoring of either production or closure of facilities would be better than a simple, declared moratorium. The generally accepted approach for verifying a global fissile material production cutoff treaty is to apply IAEA safeguards to uranium enrichment and reprocessing plants to ensure that material produced is not diverted for weapons purposes. Production reactors might or might not be subject to verification. Material accounting and control at operating plants would be a minimum requirement, while non-operating (closed, decommissioned or dismantled) plants would be subject to a set of measures specifically designed to ensure that they were no longer operating. To eventually achieve complete denuclearization, North Korea’s existing fissile material needs to be accounted for. Verifying the end of fissile material production for weapons can focus exclusively on the production facilities. By contrast, a monitored end of production could appeal to North Korea for its potential to provide technical assistance (in accounting, safety and security), to keep some facilities operating and workers engaged, and to preserve a future civilian nuclear energy option. However, like other nuclear weapon states, North Korea might also find it useful to safely close down, clean out and decommission if not dismantle its reactor and reprocessing plants to keep monitoring to a minimum. On the uranium side, Pyongyang might be less inclined to verifiably shut down the country’s facilities, reasonably arguing that its enrichment plant could be used to make fuel for the experimental light water reactor and research reactors for civilian uses. However, the only way to verify the facility’s exclusively peaceful activities would be to apply IAEA safeguards, perhaps with new measures developed within the context of the Iran nuclear deal, like continuous enrichment monitoring techniques. 3. Disable/dismantle Verifiably disabling or dismantling entirely North Korea’s reactor, enrichment and reprocessing plants would eliminate uncertainties at declared facilities. Examples of disabling actions at the 5 MWe reactor include removing fuel, draining pipes, pouring concrete into steam tanks and/or the reactor vessel, and other actions (like applying boron to prevent neutron flux) to make the reactor inoperable. Alternatively, North Korea could ask for assistance in preparing the reactor for interim safe storage before decommissioning. “Cocooning” reactors strips the facility down to their radioactive core (eliminating 80 percent of the auxiliary structures) and sealing them shut against the environment. The United States has “cocooned” six of the eight reactors at the Hanford plutonium production site, at a cost of about $21 million each. Disabling activities at the reprocessing plant could include removing (and destroying) hot cell equipment, glove boxes and mixer-settlers, and cutting pipes and removing key items like controllers from cells. Examples at the uranium enrichment plant include draining all vacuum and feed lines, disabling and removing control mechanisms and circuitry, cutting and removing gas feed lines, and disassembling centrifuge cascades. Dismantling is a much more extensive and expensive process, but does not require long-term monitoring once it is completed. In all of these approaches, the wildcard is whether North Korea has hidden capabilities, equipment or facilities. Measures that go beyond traditional IAEA safeguards (as in the Iran nuclear deal) will likely be necessary to build confidence in the country’s intention to no longer produce fissile material for nuclear weapons. The Bottom Line The Trump administration rejected a step-by-step approach in Hanoi, but without any fallback options, North Korea’s nuclear program will continue to grow in size and sophistication. Closer to the 2020 election, the stakes will be higher both for Trump and for Kim Jong Un to cut a deal. A verifiable halt in fissile material production needs to be the highest priority until then.
Categories (screenshot below) are organized hierarchically and represent the primary type of a new item. It is important that you assign them correctly, since the HNR website filters the page contents based on these categories. For example, a paper which applies network analysis in Archaeology should appear in the category “Ancient History and Archaeology”. Tutorials go in Resources/Tutorials. The easiest way to assign an item to a category is by selecting the category first and then use the Zotero plugin to download the item. It will appear in the selected category a moment later. Of course you can also add a new item manually in Zotero. Tags (screenshot below) are used to further classify items. At this stage, the library has typically only assigned one tag to an item, which corresponds to the category. A lot of additional tagging is needed. Whenever you add an item, please add the tag representing the name of the category first and then think of other useful tags. To avoid an atomization of the library, make sure that you consider existing tags first. The purpose of tags is to allow users far more specialized searches within the Zotero Library, not on the website. Always double-check before you edit or delete any items in the Library, remember you have full write access! Zotpress, the plugin which connects Zotero to WordPress requires a manual update which will occur every Friday. So don’t worry if your additions don’t appear on the site right away.
Economic prospects for a new antimalarial drug. The market for antimalarial drugs consists of the 2.8 billion (2.8 x 10(9) people living in malaria endemic areas and about 20-30 million people, mainly Europeans and North Americans, who travel or live in malarious areas, and the wealthy elite of malarious developing countries. Some of the largest markets include China, India, and Indonesia with a total of 1.9 billion people exposed; Latin America, with 119 million; and sub-Saharan Africa with 400 million. An estimated 200 million clinical cases occur each year, with around 2 million deaths annually, primarily in African children. Antimalarial drugs are distributed through several different networks and are purchased by governments and private individuals. At present the world market is dominated by chloroquine by virtue of its safety, wide availability and low price. Approximately 20% of the total production of chloroquine was distributed through national control programmes and 80% through other channels; chloroquine is probably the second or third most widely consumed drug in the world. The global market for antimalarial drugs is likely to be of the order of US$100-120 million, with chloroquine making up about US$64-80 m, sulfadoxine/pyrimethamine about US$20 m, and other drugs making up US$10-20 m. Chloroquine is rapidly losing its effectiveness against the malaria parasite, and a safe, effective, cheap replacement is urgently needed. Another product which was found to be safe and effective against malaria, with a price per treatment held at or near the present price of chloroquine, could quickly replace chloroquine as the first-line treatment against malaria.(ABSTRACT TRUNCATED AT 250 WORDS)

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