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Spencer West
Inspirational Adventurist and Expert on Overcoming Stereotyping and Bullying
Disability, Inspirational Speakers
Spencer West Biography
The life of visionary and activist Spencer West has been marked by both obstacles and triumph. After losing both legs from the pelvis down at the age of five, he entered a world that might have easily defeated him. Instead, he tackled challenge after challenge, learning to navigate in a world set against those with disabilities. His many accomplishments and lessons learned along the way, led him to discover the techniques business leaders, professionals, educators and young people can use to redefine possible in their own lives and careers.
Whether headlining corporate conferences, mesmerizing audiences in 20,000-seat stadiums, or leading volunteer excursions for youth and adults, Spencer's words and actions have encouraged millions to stand up, face challenges and embrace change. Everyone leaves with pertinent lessons they can apply to redefine what their possible is.
Spencer's incredible story is documented in both film and print. His journey is featured in the documentary Redefine Possible: The Story of Spencer West, which debuted at the Toronto International Film Festival and in his book Standing Tall: My Journey.
Demi Lovato invited Spencer to open her show on her world tour across North America, where he spoke to and inspired thousands of her fans. He has appeared countless times in the media (ABC News, 60 Minutes, CTV, BBC, TMZ and CNN).
As a featured speaker and co-host of WE Day he has graced over 60 WE Day stages across Canada, the United States and the United Kingdom. He has spoken alongside luminaries and performers such as Canada's Prime Minister Justin Trudeau, Prince Harry, former U.S. Vice-President Al Gore, Mia Farrow, Martin Luther King III, Jennifer Hudson, Natalie Portman, and Miss Piggy, to name a few.
The life lessons Spencer has learned on his personal journey speak profoundly to audiences facing their own challenges. Spencer's inspiring words have reached millions of listeners around the world, including corporations, students, educators, faith-based groups and families. Infused with humor and humility, Spencer's talks offer take-home tips and life-lessons on how to find opportunity in every challenge, while instilling hope and empowering leaders to motivate others to create positive change.
When Spencer is not inspiring audiences from the speaking platform, he is helping others to create lasting change by facilitating international volunteer trips in communities where ME to WE's charity partner works.
Contact a speaker booking agent to check availability on Spencer West and other top speakers and celebrities.
Discovery 16: Spencer West Keynote Address Highlights
Spencer West - Double Amputee | Motivational Speaker
Spencer West: Let's Start Climbing Together
Spencer West - We Day Minnesota
Standing Tall: My Journey
Redefine Possible: Lesson for Tackling Mountains in the Corporate World
Spencer West invites corporate audiences to experience the transformation that can occur when we "redefine possible". With his trademark humor and humility, Spencer spins a spellbinding story of the challenges he faced after losing his legs from the pelvis down at age five, and the journey of discovery that ultimately enabled him to summit Mount Kilimanjaro using his hands and wheelchair. Spencer applies the insights gleaned from a lifetime of overcoming obstacles to help leaders and employees identify their own roadblocks and push past them. His inspiring message and tangible life lessons motivate business audiences to believe they can tackle any goal, whether personal or professional. Spencer is the author of the best-selling book Standing Tall: My Journey, and star of the documentary Redefine Possible: The Story of Spencer West, which premiered at the Toronto International Film Festival in 2012.
Why Asking For Help Is A Sign Of Courage With Spencer West
Spencer West, who doesn't have legs, climbed nearly 20000 feet to the summit of Mount Kilimanjaro to provide clean water to over 12000 people in East Africa.
Spencer West, man with no legs, making 300-km journey through ...
Spencer West, who lost all of his lower body as a child to a congenital defect, has been using his narrow wheelchair and walking on his glove-covered hands.
HOW TO BOOK Spencer West?
Our booking agents have successfully helped clients around the world secure talent like Spencer West for speaking engagements, personal appearances, product endorsements, or corporate entertainment for over 15 years. The team at All American Entertainment represents and listens to the needs of organizations and corporations seeking to hire keynote speakers, celebrities or entertainers. Fill out a booking request form for Spencer West, or call our office at 1.800.698.2536 to discuss your upcoming event. One of our experienced agents will be happy to help you get pricing information and check availability for Spencer West or any other celebrity of your choice.
HOW MUCH DOES IT COST TO BOOK Spencer West?
Booking fees for Spencer West, or any other speakers and celebrities, are determined based on a number of factors and may change without notice. Pricing often varies according to the circumstances, including the talent's schedule, market conditions, length of presentation, and the location of the event. Speaker fees listed on this website are intended to serve as a guideline only. In some cases, the actual quote may be above or below the stated range. For the most current fee to hire Spencer West, please fill out the booking request form or call our office at 1.800.698.2536 to speak with an experienced booking agent.
WHO IS THE AGENT FOR Spencer West?
All American Entertainment has successfully secured celebrity talent like Spencer West for clients worldwide for more than 15 years. As a full-service talent booking agency, we have access to virtually any speaker or celebrity in the world. Our agents are happy and able to submit an offer to the speaker or celebrity of your choice, letting you benefit from our reputation and long-standing relationships in the industry. Fill out the booking request form or call our office at 1.800.698.2536, and one of our agents will assist you to book Spencer West for your next private or corporate function.
All American Speakers is a "buyers agent" and exclusively represents talent buyers, meeting planners and event professionals, who are looking to secure celebrities and speakers for personal appearances, speaking engagements, corporate entertainment, public relations campaigns, commercials, or endorsements. We do not exclusively represent Spencer West or claim ourselves as the exclusive booking agency, business manager, publicist, speakers bureau or management for Spencer West or any other speaker or celebrity on this website. For more information on how we work and what makes us unique, please read the AAE Advantage.
Story Musgrave, M.D.
Retired NASA Astronaut; Physician & Professor at Art Center...
Matt Roloff
Star of "Little People, Big World"
Kyle Maynard
Inspirational Athlete; Author; Entrepreneur & Two-time ESPY...
World-Famous Animal Scientist, Autism Self-Advocate &...
Former One-Handed Major League Baseball Pitcher
Noah Galloway
U.S. Army Veteran, Amputee & Finalist on "Dancing With The...
Lauren Potter
Actress Best Known for "Glee;" Special Needs Advocate
Former "Dancing with the Stars" Contestant & Paralympic...
Brad Snyder
Two-Time Paralympic Gold Medalist Swimmer & Navy Veteran
World's 1st Armless Pilot
Rocky Bleier
Former NFL Football Player, Wounded Vietnam Veteran &...
Jodee Blanco
Bullying Expert & Activist; Author of "Please Stop Laughing...
Vince Papale
Former NFL Player & Inspiration for the Movie "Invincible"
Maysoon Zayid
Palestinian-American Actress, Writer, Comedian & Disability...
Spencer West Videos
Spencer West Books
Speaker Lists Featuring Spencer West
Inspiring Expert Speakers on Disabilities
Nearly twenty percent of Americans have some sort of impairment, making disability awareness a huge priority across the nation. These inspiring speakers address disabilities and raise awareness for people living with them....
Spencer West Speaking Topics
FAQs on booking Spencer West
Spencer West is a keynote speaker and industry expert who speaks on a wide range of topics . The estimated speaking fee range to book Spencer West for your event is $10,000 - $20,000. Spencer West generally travels from TorontoCanada and can be booked for (private) corporate events, personal appearances, keynote speeches, or other performances. Similar motivational celebrity speakers are Story Musgrave, M.D., J.R. Martinez, Matt Roloff, Kyle Maynard and Shannon Miller. Contact All American Speakers for ratings, reviews, videos and information on scheduling Spencer West for an upcoming event.
Spencer West Speaker Videos
Spencer West News
Provide you with the speaking fee to book Spencer West or other celebrity appearance fees
Speakers Similar to Spencer West
Retired NASA Astronaut; Physician & Professor at Art Center College of Design
Inspirational Athlete; Author; Entrepreneur & Two-time ESPY Award Winner
World-Famous Animal Scientist, Autism Self-Advocate & Author of "Thinking in Pictures: My Life With Autism"
U.S. Army Veteran, Amputee & Finalist on "Dancing With The Stars"
Former "Dancing with the Stars" Contestant & Paralympic Professional Snowboarder
Former NFL Football Player, Wounded Vietnam Veteran & Purple Heart Recipient
Bullying Expert & Activist; Author of "Please Stop Laughing at Me"
Palestinian-American Actress, Writer, Comedian & Disability Advocate


Colorado Springs, Colo. (May 10, 2017)—Inspired by Fulcrum Media's coverage of women in ultimate at last year's National Championships, USA Ultimate is engaging the production company to expand upon that concept and further showcase female athletes in the mixed and women's divisions.
All totaled, USA Ultimate and Fulcrum will record a minimum of 74 women's and mixed division games across the 2017 College Championships, U.S. Open and National Championships, generating a library of women's-specific video that will be used to create content such as highlight reels, athlete and team profiles, Top-10 lists, complete game footage, and more.
"Each year, when I attend our premier events, I am inspired by the amazing grace and grit of these athletes," commented Tom Crawford, USA Ultimate CEO. "This project ensures we'll capture many of those moments for all to enjoy as we celebrate and promote these amazing athletes."
"The project that Callie Mah and the Fulcrum team led last year in Rockford did a remarkable job of highlighting many of ultimate's top athletes and teams, and we wanted to emulate that concept and take it to the next level," explained Andy Lee, managing director of marketing, communications and brand. "We were proud to help subsidize the original campaign alongside many other members of the ultimate community. Ultimately, that experience inspired us to reach out to Fulcrum in January to develop a plan that would replicate that idea on a grander scale."
Last fall, USA Ultimate designated and approved a $50,000 budget to support a media campaign designed to promote women in ultimate. This initial investment will fund labor, equipment rental and travel and accommodation for Fulcrum's production team, plus inventory and curation of all game footage and some video editing. In order to maximize the coverage with a consistent and comprehensive stream of content following the events, USA Ultimate and Fulcrum will team up later this year to seek additional funding for further video editing.
"Fulcrum Media is honored to be storytellers of our great sport," added co-owner Luke Johnson. "We are excited to be partnering with USA Ultimate during 2017 to tell stories that profoundly matter and showcase athletes worthy of the spotlight."
Coverage begins at the 2017 USA Ultimate College Championships in Mason, Ohio, May 26-29 where a dedicated crew of six from Fulcrum Media – editors Callie Mah and Jesse Shofner and camera operators Eddie Chan, Roberto Flores, Cam Hodgkinson and Luke Johnson – will capture at least 27 women's division games on film.


Ariane Constructions builds bespoke, high-end, low energy and energy-positive houses in the Gironde and Atlantic coast regions of France. For 6 years, for each house sold, Ariane Constructions finances tree planting on our Agroforestry project in Peru.
Jardin BiO' is an innovative and committed brand of gourmet, organic foods. As a member of the 1% For the Planet global network, the company gives 1% of its turnover to environmental protection activities, notably the Maya Nut Tree project in Colombia.
Maisons du Monde is a producer and retailer of multi-style furniture and home furnishings. «Engageons nous», our CSR approach, is built on four pillars : purchase as a partner, design as a visionary, trade as a citizen and commit as a believer. As we are particularly concerned with wood and leather products we support the Maya Nut and sustainable cattle ranching project in Colombia and build awareness among our employees of this concrete approach to maintaining biodiversity through our programme of Solidarity Leave.
The Man and Nature Foundation develops conservation strategies in partnership with local communities. To ensure their sustainability, Man & Nature works to secure the involvement of the private sector. Man & Nature is a strong supporter of the Maya Nut project and of sustainable farming initiatives.
Agence Micro Projets partners and finances small French Associations running international solidarity micro-projects. The agency supported the Envol Vert Sylvopasture project in Nicaragua from 2014 to 2016 and has supported our Maya Nut and sustainable cattle ranching project since 2017.
In 2015 Daisy Tarrier was a prize-winner in The Yves Rocher Foundation's « Terre de Femmes » initiative for the Sylvopasture project in Nicaragua. The Foundation continues to support Envol Vert via their Coup de Pouce initiative.
Lush produces and markets fresh and handmade cosmetics made with organic fruits and vegetables, essential oils of the highest quality, and safe synthetic products. Lush supports the Peru Ecotourism project.
Lilo is a search engine which forwards advertising revenue from your own online searches to social and environmental projects. Give meaning to your searches with Lilo !
Aventure Colombia, with their experience and deep local knowledge are the pioneers of responsible tourism in Colombia. They help finance our reforestation projects in Colombia by making a contribution for each tourist visiting Colombia using their services.
The French Embassy in Colombia supported Envol Vert during the 2015 edition of the Colombiodiversidad festival together with many other associations and partners who contributed. More here.
The RAJA-Danièle Marcovici Foundation supports projects around the world which favour women. Since 2017 the Foundation has supported our Maya Nut Tree project in Colombia.
The eco.business Fund is a joint initiative of investors' intent on supporting the promotion of business and consumption practices that contribute to biodiversity conservation, the sustainable use of natural resources, climate change mitigation and adaptation to its impacts. Collaborate with Envol Vert subsiding the Festival Colombiodiversidad in Colombia.
Envol Vert is member of the "1% For the Planet" club. Since 2002, 1% for the planet encourages businesses to donate 1% of their profits to environmental organisations across the globe.
Since 2017 La Redoute has supported Envol Vert through activities focused on reforestation such as the sale of « Make your Planet Great Again » t-shirts where a percentage of revenue goes to Envol Vert.
Voyageurs du Monde, Comptoir des Voyages, Terres d'Aventure (brands of Terres d'Aventure and Grand Nord Grand Large) and Nomade Aventure have created the Fondation Insolites Bâtisseurs, which promotes the reduction of North / South inequalities by supporting humanitarian programmes and encourages tourism companies to share their values.
The AFD (Agence Française de Développement) present in Colombia supports the Colombiodiversidad festival promoting Colombian biodiversity across several Colombian cities.
AAAEnergie supports Envol Vert by donating computer and multimedia equipment.
Located in La Rochelle, a town with a longstanding reputation as a pioneer in environmental protection, the Imprimerie Rochelaise (La Rochelle printing works) has been working at the cutting edge of sustainable development for almost 10 years. The Imprimerie Rochelaise also supports Envol Vert's work by printing our material free of charge.
Nouveau Monde and Alexis Tricoire help fund Envol Vert through the sale of the plants used in their installations such as the Two Headed Dragon at the Cité de la Mode in Paris or the Green Cabin displayed at the Grand Palais in Paris during COP 21.
Australie – the independent advertising agency – creates communication concepts for Envol Vert for free !
In 2015 was supported by two charity at the checkout initiatives run by the licenced provider microDON : these were L'ARRONDI (rounding up to nearest euro) at the checkouts of Nature et Découverte stores and microDON Paris 2015 at Franprix supermarkets.


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Home/Destinations/Mediterranean/Valletta, Malta
CRUISE TO LUXURIOUS VALETTA, MALTA
Tiny Malta, smack dab in the middle of the Mediterranean and on everyone's route since ships began to ply the seas, is packed with history from top to bottom. Over time it was ruled by a variety of empires, all of which contributed to the look and culture of the islands. Valetta is a living museum of baroque architecture, constructed by the Knights of St. John five centuries ago. Today the city is also a dynamic hub of cultural and commercial activity, its harbour now welcoming luxury yachts and cruise ships.
Featured Valletta, Malta Voyages
10-Night Dalmatian & Amalfi Voyage
11-Night Islands Of The Mediterranean
View all Valletta, Malta voyages
Valletta, Malta Highlights
Grand Master's Palace
Visit the Parliament of Malta's offices, formerly a residence of the Knights of St. John.
Tarxien Temples
Discover the ancient ruins of this intricate temple complex from 3000 BC.
Island Panoramic Drive
Explore historic and picturesque villages including Vittoriosa, Marsaxlokk, Mdina, and Girgenti. Highlights include the Blue Grotto at Wied iz-Zurrieq, the Buskett Gardens, Malta's highest point, the Dingli Cliffs, and Mosta's famous domed church.
Featured Valletta, Malta
Walking#Follow a local guide on an eye-opening stroll through a historic city, rural community, or traditional village.
Jewels of the Maltese Capital
Enjoy a guided sightseeing adventure through Malta's capital city with a special visit to its greatest architectural treasure, St. John's Co-Cathedral.
Sightseeing#Embark on a locally guided journey that's ideal for first-time visitors and those seeking the premier vistas and landmarks of a destination.
Naxxar and Mdina: Palaces, Cathedrals & Gardens
Stroll through the opulent chambers of a palace passed down by a Malta family for generations, then discover the great landmarks and storied history of Mdina.
Salt Pans, Local Artisans and Traditional Games
Visit historic salt pans and learn about the harvest from a local expert; meet island artisans; and spend some time in a local village.
View All Valletta, Malta Shore Excursions
Valletta, Malta At a glance
GPS: 35°53'52.04"N 14°30'50.78"E
Size: 0.80 KM2 (0.31 MI2)
Density: 8,344 Pop/KM2 (3,222 Pop/MI2)

redpajama_set_name: RedPajamaCommonCrawl


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Tags Implementation
Open Call for Board Members — Forward Through Ferguson
Overview | Who We're Looking For | How to Apply | Selection Timeline
Forward Through Ferguson seeks to add four to six new members to our Board of Directors.
Share on Facebook | Share on LinkedIn | Tweet the Call
Forward Through Ferguson (FTF) is the nonprofit organization formed to carry on the work of the Ferguson Commission. FTF's mission statement: Embracing the Ferguson Commission's mandate, Forward Through Ferguson centers impacted communities and mobilizes accountable bodies to advance racially equitable systems and policies that ensure all people in the St. Louis region can thrive. FTF's focus is to serve as conscience and catalyst in leading our region on a path toward Racial Equity—a St. Louis where outcomes are no longer predictable by race—by advancing a three-pronged strategy:
Advocating for policy and systems change;
Strengthening regional capacity for Racial equity work; and
Securing financial sustainability for FTF and a regional Racial Equity Fund.
(Learn more at forwardthroughferguson.org/implementation-2/)
As a Board, we are particularly focused on:
Strengthening the organizational infrastructure to sustain and expand the work of FTF moving forward;
Developing a robust fundraising program that allows FTF to fund its work and mission, and catalyze the work of others to advance racial equity;
Creating a Community Governance model that centers and elevates the voice of the community that volunteered more than 30,000 hours ours to compile an exhaustive policy roadmap following the uprising after the killing of 17-year old Michael Brown, Jr. in 2014; and
Supporting the Lead Catalyst and staff in implementing the three-pronged strategic plan.
Through this work, we are committed to helping our region by:
Championing a regional understanding of Racial Equity, why it matters, and how it differs from diversity, inclusion, and equality;
Serving as a catalyst to bring key regional players and accountable bodies to shared tables;
Challenging institutions to support Racial Equity and to use their influence to do so;
Connecting those institutions and others doing this work with the partners and resources they need to effect change;
Shining a light on racial inequity and amplifying efforts of those institutions addressing it;
Monitoring and reporting on our region's progress in responding to the Calls to Action outlined in the Ferguson Commission report; and
Remaining accountable to the thousands of St. Louisans who participated in the development of the Report, people of color, and systemically disadvantaged communities.
We're looking for you if you have some combination of the following:
Board experience (either non-profit or for-profit) and can see clearly how the board structure can be leveraged to support experimentation, risk, and unproven strategies;
No board experience, but are an engaged member of a community organization who feels your voice and perspective is often missing in board or executive-level deliberations and decision-making;
Ideas about how to create a new Community Governance model that includes youth voice and creates accountability between the fiduciary board of FTF and the community whose reality and racial equity aspirations it represents;
Represent "youth voice" through your lived experience/expertise;
Experience with policy change (Big "P" and little "p") as a policymaker, advocate, community organizer or other changemaker role;
A communications background that will help us amplify the work of FTF in traditional media outlets, digital media platforms, and community-based networks;
Experience, ideas, and energy around transformative resource development.
Expertise and experience in nonprofit finance and robust financial procedures.
Commitment to practicing radical listening and collaboration;
A growth mindset that questions the default and is comfortable challenging the status quo; and
Don't want or need another line on your resume, don't expect much praise or glory, and don't need this work to feed your ego, but deeply, passionately give a damn and are willing to be vulnerable in doing work that is often unprecedented, scary and overwhelming.
Interested? Here's what we need to know:
Why does this matter to you?
Who vouches for you as a great fit and why (in their words)?
The core principles of this work are Racial Equity, Radical Listening, Policy over Programs, and Collaboration. What does that mean to you and/or to our region specifically?
How do you anticipate contributing to the sustainability of the organization and the execution of our strategic plan through policy work, community governance, fundraising and/or racial equity capacity experience/expertise?
Your submission can take whatever form you feel expresses you best—from a traditional cover letter, resume, and letters of recommendation to a video, manifesto, or vision board.
Whatever the format, cover all the bases and submit everything to board@forwardthroughferguson.org (for #2, have them submit their thoughts to you to deliver with the rest of your answers or have them send directly to us on your behalf using this address).
If you would like to nominate someone for this board, please submit their contact information at https://bit.ly/FTF_BoardNomination.
Selection Timeline:
Application packets are due by 11:59 AM on September 16.
We will interview candidates this fall and make selections by the end of the year. We will share a more detailed timeline with candidates who reach the finalist stage.
If you have questions about the process that are not answered here, please submit them to board@forwardthroughferguson.org.


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Beryozovka () is a rural locality (a selo) and the administrative center of Beryozovskoye Rural Settlement, Vorobyovsky District, Voronezh Oblast, Russia. The population was 376 as of 2010. There are 16 streets.

Geography
Beryozovka is located 9 km northeast of Vorobyovka (the district's administrative centre) by road. Muzhichye is the nearest rural locality.

References

Rural localities in Vorobyovsky District

redpajama_set_name: RedPajamaWikipedia


The Astra Sports Tourer has similar exterior dimensions to the outgoing model but due to clever packaging offers more interior space for passengers and increased luggage space for their belongings. The array of useful technology available in both body styles, including OnStar emergency personal assistance with 4G WiFi and IntelliLink infotainment system, increases convenience and security. At the same time a capable range of petrol and diesel engines offer power outputs from 105PS to 200PS. Furthermore, Co2 emissions from as low as 89g/km make the Astra Sports Tourer a particularly appealing choice to business users. Little wonder that the Astra was voted European Car of the Year for 2016.
The 1.6 litre CDTi S/S ecoFLEX unit is particularly impressive with regard to efficiency. It returns combined fuel economy of up to 85.6mpg and CO2 output of only 88g/km, making it a great choice for drivers who regularly travel long distances; as its name suggests, it is also notably quiet and refined. The choice of petrol engines available, meanwhile, offer eager performance and a swift throttle response - especially the 1.0 litre 105PS and 1.4 litre 150PS turbocharged units. A finely calibrated five- or six-speed manual or automatic transmission ensures that acceleration is always smooth and rapid.
The Astra is available from £17,115, the below are our two feature models.
Vauxhall and York Ward & Rowlatt are not responsible for the provision of the OnStar and Wi-Fi services, which are provided by OnStar Europe Limited, a GM Company. All OnStar services and Wi-Fi services will cease to be available on December 31st, 2020. No trial or paid subscriptions or services, including emergency response services, will be available after that date.


text:
/***********************************************************************
    created:    11/8/2012
    author:     Lukas E Meindl
*************************************************************************/
/***************************************************************************
 *   Copyright (C) 2004 - 2012 Paul D Turner & The CEGUI Development Team
 *
 *   Permission is hereby granted, free of charge, to any person obtaining
 *   a copy of this software and associated documentation files (the
 *   "Software"), to deal in the Software without restriction, including
 *   without limitation the rights to use, copy, modify, merge, publish,
 *   distribute, sublicense, and/or sell copies of the Software, and to
 *   permit persons to whom the Software is furnished to do so, subject to
 *   the following conditions:
 *
 *   The above copyright notice and this permission notice shall be
 *   included in all copies or substantial portions of the Software.
 *
 *   THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
 *   EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF
 *   MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT.
 *   IN NO EVENT SHALL THE AUTHORS BE LIABLE FOR ANY CLAIM, DAMAGES OR
 *   OTHER LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE,
 *   ARISING FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR
 *   OTHER DEALINGS IN THE SOFTWARE.
 ***************************************************************************/
#include "HelloWorld.h"
#include "CEGUI/CEGUI.h"

#include <iostream>

/*************************************************************************
    Sample specific initialisation goes here.
*************************************************************************/
bool HelloWorldDemo::initialise(CEGUI::GUIContext* guiContext)
{
    using namespace CEGUI;
    // execute the HelloWorldDemo script which controls the rest of this demo
    System::getSingleton().executeScriptFile("HelloWorldDemo.lua");

    System::getSingleton().getScriptingModule()->executeScriptedEventHandler("HelloWorldDemo.initialize", CEGUI::GUIContextEventArgs(guiContext));
    return true;
}

/*************************************************************************
    Cleans up resources allocated in the initialiseSample call.
*************************************************************************/
void HelloWorldDemo::deinitialise()
{
}

/*************************************************************************
    Define the module function that returns an instance of the sample
*************************************************************************/
extern "C" SAMPLE_EXPORT Sample& getSampleInstance()
{
    static HelloWorldDemo sample;
    return sample;
}

redpajama_set_name: RedPajamaGithub


text:
Caracas,
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Panama World Boxing Champ Writing Autobiography
PANAMA CITY – A "mistake" he made sent him to prison and after several years of purgatory Panamanian former world boxing champion Celestino "Pelenchin" Caballero, who passed like a meteor through the decade after 2000 in the super-bantamweight category, is making public his "truth" in a book titled "Mi ultimo round" (My last round) to reconnect with the taste of "victory" and "create awareness."
The book is an autobiography in which the 43-year-old Caballero, who retired from the ring in 2014, reflects on what happened on March 10, 2016, at a police roadblock where he was stopped with 10 kilograms of cocaine, spending five years behind bars for the crime.
Caballero, who built up a record of 37 wins (24 by knockout) and 6 defeats, was released in May 2018 after a Panamanian court commuted his sentence, changing the remainder to community service.
"After what happened to me and my release ... I said it's time to do the book," Caballero told EFE in an interview, adding that in writing it he is seeking to "guide" public opinion and "raise awareness."
The champ, born in the impoverished province of Colon on Panama's Caribbean coast, writes about his life from the "beginning" and about "all" that he has "had to experience and live through" to get to this moment in his life, where he claims to feel "good and happy."
"God forgave me. ... (God) knows my heart. I feel good and I'm happy. It's human beings that treat each other badly, not God. I'm moving forward positively and here I'm in my new phase and I hope to have others," the winner of the World Boxing Association and International Boxing Federation super bantamweight titles between 2006 and 2010 and the WBA regular featherweight title from 2011-2012 said.
Upon being questions why he titled the book as he did, Caballero didn't hesitate: "It's called 'My last round' because in boxing you have to fight with everything ... with strength, faith and a lot of intelligence."
"The last round is the victory round. It's the round in which you have to overcome your rival, it's the one in which you have to shine, it's the one that gives you the victory in life or in your career," said the Panamanian pugilist.
He revealed that during the creative process for the book, published by the local LatinBeat Studios, the most painful part was discussing that moment when the authorities apprehended him with drugs.
"In this book I explain why I made that mistake. It's painful to know that ... your country has turned its back on you. It's sad, but OK in the book I write about how everything was. I hope that people can buy it and know the why of things," he said.
Writing this book, which will be released at the 2019 Panama International Book Fair, which begins on Tuesday, "was more difficult" than boxing, he said, because "I did it having two feelings: joy and sadness."
"Boxing always gave me joy, despite the defeats," Pelenchin said, adding that that's why he misses his time in the ring, calling it – without a doubt – one of the best parts of his life.
Caballero, who described himself as a "humble, simple, happy, always accommodating" man, promised that this "last round" will be similar to when he put on his gloves "to go out and win."
The Panama International Book Fair is devoting this year's edition to the 500th anniversary of the founding of Panama City and will feature writers from Spain, France, Portugal, Colombia, Mexico, the United States, Cuba, Guatemala, Peru, Argentina and Panama.
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Exceedingly comfortable 100% cotton material allows you to relax and feel at peace in the most strenuous poses.
You can apply as much pressure to this belt as you need, thick, wide material is strong, durable and has heavy cotton webbing sewn throughout.
You will be able to hold poses for long periods of time without interruption.
Relax knowing you won't mix up your belt with someone else's, even at the most crowded studio or class.


This is a very unique sensor. We haven't seen anything else that is affordable and accurate for measuring liquid level. This sensor seems like it would be a handy addition to a hydroponics, aquarium, fountain, or pool controller, or perhaps measuring a rain tube. This particular sensor is the 5" version, and it includes a 4-pin connector and 560 Omega 5% resistor. The connector is so you don't have to solder directly to the delicate pins. Instead, just solder to the connector and plug it onto the sensor.
Since the sensor is resistive, it is easy to read it using a microcontroller ADC pin. Check the tutorials tab for a quick-start pointer!
Please Note: This product only comes with the 5" bare Tape Liquid Level Sensor. In our demo, we set up a 12" enclosed version with an Adafruit Metro, a TB6612 Stepper Motor Driver Breakout Board, and an Automotive Gauge Stepper Motor to demonstrate functionality.
Product Dimensions: 165.0mm x 25.0mm x 0.8mm / 6.5" x 1.0" x 0.0"


text:
Unterirdische Moscheen sind Moscheen, deren Räume und Einrichtung sich unter der Erdoberfläche befinden. Sie wurden entweder unter anderen Gebäuden errichtet oder liegen mit unauffälligem Erscheinungsbild frei im Boden. Die Gebetsräume unterirdischer Moscheen sind meist sehr klein, auch besitzen sie keine Minarette. Unterirdische Moscheen sind sehr selten zu finden, so auf Djerba und in Istanbul.

Verbreitung

Djerba

Im Süden der tunesischen Insel Djerba findet sich eine unterirdische Moschee nahe der Ortschaft Sedouikech. Sie wird nicht mehr für Gebete genutzt und kann besichtigt werden. Auch in der Nähe von Ajim ist eine Moschee dieser Art zu finden. Sie diente als versteckte Gebetsstätte der Ibaditen.

Istanbul
In Istanbul befindet sich die unterirdische Moschee Yeraltı Camii. Sie wurde im 18. Jahrhundert errichtet und liegt heute im Stadtteil Galata. Ursprünglich befand sich die Moschee unter einer Festungsanlage, die heute nicht mehr vorhanden ist.

Jerusalem
Ende des 20. Jahrhunderts wurde begonnen, die unterirdischen Anlagen der Ställe Salomos auf dem Tempelberg zu einer unterirdischen Moschee umzubauen. Die Marwani-Moschee ist die größte unterirdische Moschee der Welt und fasst mehrere tausend Menschen. Die Baumaßnahmen sind äußerst umstritten. Dem islamischen Waqf, der den Tempelberg verwaltet und die Bauarbeiten veranlasste, wird vorgeworfen, durch den Bau der Moschee bedeutende archäologische Zeugnisse der jüdischen Vergangenheit des Heiligen Ortes zu zerstören. Im Aushub der Bauarbeiten wurden archäologische Funde gemacht, die dem Salomonischen Tempel zugeordnet werden.

Weblinks

Einzelnachweise

Moschee nach Typ
Sakraler Höhlenbau


Tap The Thumbnail Bellow to See Related Gallery of "Kitchen Countertop Material DanSupport Intended For Plan 15"
Image Title: Kitchen Countertop Material DanSupport Intended For Plan 15. Filename: kitchen-countertop-material-dansupport-intended-for-plan-15.jpg. Image Dimension: 640 x 424 pixels. Images Format: jpg/jpeg. Publisher/Author: Henry Jenkins. Uploaded Date: Tuesday - February 20th. 2018 15:17:14 PM. Category: Architecture. Image Source: homedit.com.


text:
"""Support for Tuya fans."""
from homeassistant.components.fan import (
    DOMAIN as SENSOR_DOMAIN,
    ENTITY_ID_FORMAT,
    SUPPORT_OSCILLATE,
    SUPPORT_SET_SPEED,
    FanEntity,
)
from homeassistant.const import CONF_PLATFORM, STATE_OFF
from homeassistant.helpers.dispatcher import async_dispatcher_connect

from . import TuyaDevice
from .const import DOMAIN, TUYA_DATA, TUYA_DISCOVERY_NEW

PARALLEL_UPDATES = 0

async def async_setup_entry(hass, config_entry, async_add_entities):
    """Set up tuya sensors dynamically through tuya discovery."""

    platform = config_entry.data[CONF_PLATFORM]

    async def async_discover_sensor(dev_ids):
        """Discover and add a discovered tuya sensor."""
        if not dev_ids:
            return
        entities = await hass.async_add_executor_job(
            _setup_entities, hass, dev_ids, platform,
        )
        async_add_entities(entities)

    async_dispatcher_connect(
        hass, TUYA_DISCOVERY_NEW.format(SENSOR_DOMAIN), async_discover_sensor
    )

    devices_ids = hass.data[DOMAIN]["pending"].pop(SENSOR_DOMAIN)
    await async_discover_sensor(devices_ids)

def _setup_entities(hass, dev_ids, platform):
    """Set up Tuya Fan device."""
    tuya = hass.data[DOMAIN][TUYA_DATA]
    entities = []
    for dev_id in dev_ids:
        device = tuya.get_device_by_id(dev_id)
        if device is None:
            continue
        entities.append(TuyaFanDevice(device, platform))
    return entities

class TuyaFanDevice(TuyaDevice, FanEntity):
    """Tuya fan devices."""

    def __init__(self, tuya, platform):
        """Init Tuya fan device."""
        super().__init__(tuya, platform)
        self.entity_id = ENTITY_ID_FORMAT.format(tuya.object_id())
        self.speeds = [STATE_OFF]

    async def async_added_to_hass(self):
        """Create fan list when add to hass."""
        await super().async_added_to_hass()
        self.speeds.extend(self._tuya.speed_list())

    def set_speed(self, speed: str) -> None:
        """Set the speed of the fan."""
        if speed == STATE_OFF:
            self.turn_off()
        else:
            self._tuya.set_speed(speed)

    def turn_on(self, speed: str = None, **kwargs) -> None:
        """Turn on the fan."""
        if speed is not None:
            self.set_speed(speed)
        else:
            self._tuya.turn_on()

    def turn_off(self, **kwargs) -> None:
        """Turn the entity off."""
        self._tuya.turn_off()

    def oscillate(self, oscillating) -> None:
        """Oscillate the fan."""
        self._tuya.oscillate(oscillating)

    @property
    def oscillating(self):
        """Return current oscillating status."""
        if self.supported_features & SUPPORT_OSCILLATE == 0:
            return None
        if self.speed == STATE_OFF:
            return False
        return self._tuya.oscillating()

    @property
    def is_on(self):
        """Return true if the entity is on."""
        return self._tuya.state()

    @property
    def speed(self) -> str:
        """Return the current speed."""
        if self.is_on:
            return self._tuya.speed()
        return STATE_OFF

    @property
    def speed_list(self) -> list:
        """Get the list of available speeds."""
        return self.speeds

    @property
    def supported_features(self) -> int:
        """Flag supported features."""
        supports = SUPPORT_SET_SPEED
        if self._tuya.support_oscillate():
            supports = supports | SUPPORT_OSCILLATE
        return supports


If you would like to advertise a training opportunity on this page, please contact Janet Waterhouse at networkmanager@phyconet.org.uk.
If you would like to advertise a position on this page, please contact Janet Waterhouse at networkmanager@phyconet.org.uk.
Algae World News provides algae news and information from around the world.


This exhibition explores how European and American artists represented Indigenous North Americans in drawings, prints, watercolors, photographs, and popular ephemera from the seventeenth to the early twentieth century.
Through forty-five examples from The Met collection, the display will trace the evolution of this complex imagery over time, highlighting the ways in which it contributed to the creation and dissemination of myths and misconceptions about Native peoples, often justifying their dispossession, cultural destruction, and genocide.
From formulaic depictions of so-called savage warriors and Indian princesses to romanticized representations of a "vanishing race," these works reveal the pervasive influence of Indigenous America on the Euro-American imagination.


Ever Art Wood® Express Plank Panels in Kuri Masame and custom textured Wuoro Nato on external facade; Ever Art Wood® Flat Panels in Kuri Masame to internal lobbies.
A combination of Ever Art Wood® 2mm flat panels & Ever Art Wood® Koshi 50 x 150mm batten in 'Pain' colour; Easy Green wire trellis vertical garden.
PVDF Panel cladding - External cladding XXXXXX.
Australian Institute of Architects (AIA) Victorian Chapter 2017 Award for Residential Architecture – Houses (Multiple Housing). Designed by Woods Bagot.


text:
IRIM Robotics Seminar—Jonathan How, Massachusetts Institute of Technology
The Institute for Robotics and Intelligent Machines presents "Navigation and Mapping for Robot Teams in Uncertain Environments" by Jonathan How of the Massachusetts Institute of Technology. The event will be held in the Marcus Nanotechnology Building, Rooms 1116-1118, from 12:15-1:15 p.m. and is open to the public.
Our work addresses the planning, control, and mapping issues for autonomous robot teams that operate in challenging, partially observable, dynamic environments with limited field-of-view sensors. In such scenarios, individual robots need to be able to plan/execute safe paths on short timescales to avoid imminent collisions. Performance can be improved by planning beyond the robots' immediate sensing horizon using high-level semantic descriptions of the environment. For mapping on longer timescales, the agents must also be able to align and fuse imperfect and partial observations to construct a consistent and unified representation of the environment. Furthermore, these tasks must be done autonomously onboard, which typically adds significant complexity to the system. This talk will highlight three recently developed solutions to these challenges that have been implemented to (1) robustly plan paths and demonstrate high-speed agile flight of a quadrotor in unknown, cluttered environments; and (2) plan beyond the line-of-sight by utilizing the learned context within the local vicinity, with applications in last-mile delivery. We further present a multi-way data association algorithm to correctly synchronize partial and noisy representations and fuse maps acquired by (single or multiple) robots, showcased on a simultaneous localization and mapping (SLAM) application.
Jonathan P. How is the Richard C. Maclaurin Professor of Aeronautics and Astronautics at the Massachusetts Institute of Technology. He is a Fellow of both the IEEE and the American Institute of Aeronautics and Astronautics (AIAA), the editor-in-chief of the IEEE Control Systems magazine, and an associate editor of the AIAA Journal of Aerospace Information Systems and the IEEE Transactions of Neural Networks and Learning Systems (TNNLS). How has won multiple AIAA best paper awards, including those of 2011, 2012, and 2013. Additionally, he earned the 2011 IFAC Automatica award for the best application paper, the 2020 AIAA Intelligent Systems Award, and 2002 Institute of Navigation Burka Award.
Location: Marcus Nanotechnology Building, Rooms 1116-1118
URL: Marcus Nanotechnology Building, Rooms 1116-1118
Jonathan How
Josie Giles
IRIM Marketing Communications Manager
josie@gatech.edu
Robotics Seminar Series


Hi Paaj, thanks so much for all your work in this design.
We really like the overall and how you got our style and what we wanted!
Also, I like the gray you added, probably go with the keystone on the bed wall.
Quantity: 2 Our textured Liano pillow in monochromatic neutral layers beautifully with both solid and patterned colors. Our decorative pillows include your choice of a plush feather-down or lofty down-alternative insert at no extra cost Discount link available to project holder only 23"
MADDIE TEXTURED PILLOW COVER With a textured design in a deep color palette, this pillow cover serves as a foundation for a seasonally changing mix of patterns. Discount link available to project holder only 22"
'Through the Haze Diptych' By Christine Lindstrom 2 Piece Framed Watercolor Painting Print Set Features Arrives ready to hang Artist: Christine Lindstrom Top quality Giclée print on high-resolution archive paper Made in the USA Hand cut deckled edges Artwork by Christine Lindstrom Discount link available to project holder only 24" x 32"


text:
TechnologyGaming
It Takes Two – References & Easter Eggs You Probably Missed
By Sean Farlow
It Takes Two is a fun co-op game that will take you through numerous levels, including space, a room full of toys, and a garden. But there's a lot to find if you like to take your time with games and explore everything. Most players won't find these in one single playthrough, mainly because they are well hidden in the levels. Here are the references and Easter eggs you probably missed on It Takes Two:
A Way Out Characters
Rainbow Road
The Doll Says Bye With the Thumbs Up
Helltower Has an Achievement/Trophy
Hazelight Studios is behind It Takes Two and there are some things that the studio has hidden in the levels to remind us of previous projects. One of the cool little things that the studio has hidden can be found early on in the game.
In one of the levels, you'll be running around a bunch of pillows and other objects. At one point, you'll see that the level features a different way where you can climb and reach another section. The Easter egg can be found on the left side of the map inside a really small area. Inside, you get to see the characters from A Way Out. The 2018 co-op game is from the same studio so they are there for players to see. Leo and Vincent are right next to each other and their voice lines can be activated by jumping and sitting on the button. Achievement and trophy hunters can push the button at the same time to unlock a trophy/achievement.
Towards the end of the game, players will go on a journey across several tracks and cool looking sections. One of those is just like Rainbow Road, the tracks that appear on every Mario Kart game. It is one of the easiest Easter eggs to spot if you have played Mario Kart before.
At one point of the game, you'll see it turn into an action RPG. Both characters will be running around with different types of powers and ways to get across the walls and obstacles. Towards the end, a giant doll starts crushing everything behind you, making you run to safety. The section ends with the doll seeing the platform collapse, sending it into a pool of fire. The doll goes down but not before showing a thumbs up, similar to the scene in Terminator 2. The whole thing lasts a couple of seconds so it can easily be missed.
In the section of the game where you find the Helltower and numerous mini games, there is a little boat that both players can get on. The boat takes players around the town but in the tunnel, they can stop, hop out, and enter a door. Inside, they'll find a number of breakable pots and jars that will throw out little stones that look like Rupees from the Zelda games.
In the same town where you find the Zelda Easter egg, you'll find the Helltower. The tower does not require to be completed for the game to advance. But those looking to complete the game to 100 percent will have to reach the top. It doesn't look difficult at first glance but the tower is pretty high and it has a number of rotating platforms that go in and out.
The first part of the tower is pretty difficult and the second part doesn't get any easier. Players have to be very careful if they want to reach the top. Once up there, they'll get the Platform Prodigy achievement/trophy. They can also activate some fireworks as a celebration for reaching the top.
It Takes Two, released in March of this year, is available on PC, Xbox, and PlayStation consoles. The game was recently added to the EA Play lineup.
Previous articleJanuary Transfer Window – The Latest Rumors
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Sean Farlow
University graduate with a bachelor's degree in business administration. Big fan of sports teams from South FL.


text:
HBO and Twit.tv top Microsoft's new Flash blacklist | ZDNet
The Future of Nuclear Power Runs on the Waste of Our Nuclear Past
SEC nails Illinois, but the snake slithers away - Al Lewis - MarketWatch
Makes me wonder if I could run for office on the promise that I won't end up in jail.
Quinn was not governor when all of this happened. Rather, it was Gov. Rod Blagojevich, who retired to a federal penitentiary in Colorado.
Blagojevich, who was not mentioned in the SEC's action, was convicted on fraud in an unrelated case, including allegations he tried to sell President Barack Obama's former U.S. Senate seat. One potential buyer for this seat, according to federal prosecutors, was then-Rep. Jesse Jackson Jr., who recently pleaded guilty to felony charges after standing accused of misusing campaign funds.
Jackson, of course, was only following in the footsteps of other renowned Illinois politicians, including former Rep. Dan Rostenkowski, whose career ended in 1996 when he pleaded guilty to mail fraud.
It has long been common for Illinois politicians to retire to a prison setting. George Ryan, governor from 1999-2003, was convicted of racketeering. Dan Walker, governor from 1973-1977, pleaded guilty to bank fraud. Otto Kerner, governor from 1961-1968, was convicted of bribery.
Makers Mark: Makers Mark watering down bourbon - Chicago Tribune
the total alcohol by volume of Maker's Mark is being reduced by 3 percent!
at 3/13/2013 10:54:00 AM No comments:
'Killer dolphins' escape Ukranian naval base - UPI.com
LivingSocial's Glow-in-the-Dark 5K Dance Party - LivingSocial Fun & Events
Gentlemanly Jack and Just Plane Smart
Interesting solutions to trademark infringement.
Gentlemanly Jack
Just Plane Smart - Southwest Air
Hot Tub Boats
Yep, need one of these:
Huckberry | Hot Tub Boats
Bank of America cuts check for Estates couple in mistaken foreclosure case » Naples Daily News
Chain O Lakes Brewing
What! A brewery opening in Mchenry, IL! Only minutes from the Studio (Black Doug's House). Awesome!
Best Beer, Breweries, Chain O Lakes, Brewpubs
▼ Mar 10 - Mar 17 (10)
HBO and Twit.tv top Microsoft's new Flash blacklis...
The Future of Nuclear Power Runs on the Waste of O...
SEC nails Illinois, but the snake slithers away - ...
Makers Mark: Makers Mark watering down bourbon - C...
'Killer dolphins' escape Ukranian naval base - UPI...
LivingSocial's Glow-in-the-Dark 5K Dance Party - L...
Bank of America cuts check for Estates couple in m...


text:
Juliet Mendoza was born in the colorful city of Angels, we can say her musical background begins before she was even born. Having a mother with a professional disco dancing passion, of course one can only imagine that Juliet would genetically inherit the love of music. She started dance classes at the very young age of 5, with Jazz, Hip hop, Latin, and ballet.
Deep into the rabbit hole of Djing, Juliet's love for the music takes us back to the mid 90's, house scene. Becoming a regular in LA house clubs, such as the Arena and Carnival. By her early 20's she becomes a well-known House Dancer in the Los Angeles underground house scene, attending just about every underground house music party in L.A. By her mid-20s she found herself working as part of the promotions street team for one of the biggest electronic music promotional companies of its time,
"Go Ventures", who put on festivals such as: Monster Massive, Together As One, & The Love Festival (LA)(LV)(HI)(CO).
She is one of the Core Members of the organization "Open House" which gives the dance community in Los Angeles creative shelter where the knowledge of house dance, music philosophy and club culture is shared in a dance class environment making it affordable to the lowest of incomes by providing the community with house dance music workshops and guest speakers.
It is with this vast knowledge, influence, and drive, that Juliet undoubtedly took to the turntables by storm and never looked back.
Juliet Mendoza has shared decks with Doc Martin, Marques Wyatt, Will Reelsoul Rodriguez, Mark Di Meo, Colette, Dj Heather, David Harness, Wayne Williams, Dj Sneak, Paul Johnson, Dj Dan, Kenny Summit, Folamour, Never Dull, Jask, Oscar P, Mark Grant, Demuir and the music family keeps expanding. She is also featured on the following records : Julio Bashmore (Knocking Boots) - She Ain't / The Posse (The Labour of Love) - Just Go With It / Ben Dragon (Sexxx Tape) - Collide / Thomas Garcia - I Must Be Dreaming
Her unique style of delivering melodic, soulful and deep sounds, has taken Juliet above & beyond the boundaries of Los Angeles and the U.S to headline several international events/venues: NL Club (Amsterdam), Le Reservoir (Paris), Hookah Lounge (MX City), Mi Casa Holiday (MX Tulum), Juicy Beats (Las Vegas).
Having such a deeply rooted connection to LA house music culture, naturally gravitated to the records that inspired her to Dj. with residencies at nights such as "Thick"(LA), "Open House" (LA), "FlyBall"(LA) "House on the Eastside"(LA) "Soul Brain"(LA) & "Local Love"(LA) she is also a resident of her own night "Jill's House"aka "Jackin Jill's (LA). There is no doubt that Juliet is a truly driven ambassador to the house music movement.
Shaboom Records / Open House LA/ Jackn' Jill's


Product prices and availability are accurate as of 2019-04-21 15:27:44 UTC and are subject to change. Any price and availability information displayed on http://www.amazon.com/ at the time of purchase will apply to the purchase of this product.
This 5 inch diameter brush is produced to professional standards Bristle length is one inch and the bristles are soft. Brush attaches to most cordless drills. Now features a quarter inch quick change shaft Soft bristles for gentle scrubbing Bristles are about as soft as a toothbrush for gentle scrubbing.


What is the Personal Power of Beauty?
Beauty is the power of radiance, and your personal beauty has the power to illuminate your world to a more radiant and bountiful experience. There is abundance, joy, passion, sensuality, and pleasure to be had in your beautiful life, and working with your personal power of beauty is a strategy for claiming even more. Your personal power of beauty is a treasure to behold, a way to be bold and a powerful journey for you to unfold. Beneath the surface of your skin is the story of your beauty, and this is the story that is meant to be told.
The personal power of beauty is a magical tool that enhances all aspects of your existence to a more majestic and magnificent experience. Beauty is the source of your personal magic; it is the essence of who you are, it connects you to others and to the plenty of this planet.
What is beauty? Where does it come from? Who has it?
When you think of beauty is it something you know you have within you? Or does beauty seem like something elusive and outside of you?
All people are beautiful, and it is our essential nature to radiate this beautiful truth.
Years ago, I saw an ad that I loved for Burt's Bee's products. The photo was of a group of Harley-type bikers, you know, heavy set men, grimacing, hairy and looking kind of scary. The caption on the ad said, "The Beauty is on the Inside". It couldn't be clearer, beneath the packaging is where you will find true Beauty, it's on the Inside. This ad cracked me up, just thinking about it still makes me smile; the message was so clear, powerful and beautifully stated. Beauty comes from within, it emanates through the skin and vibrates around us.
Each of us has our own personal beauty, it is the unique essence of who we are, like our signature or thumbprint, it is exclusively our own. Our personal beauty or inner beauty stems from the heart, our center of love. Our center of love is the vital force of our spirit, and the vital force of our spirits spring from the source of all life: Whether it be God, Goddess, Great Spirit, Energy, Vibration, the Creator, Nature, the Divine or the Force it is all the same source. Whatever you believe to be the divine spark of life within you; whatever you equate to the magic of your existence; however you understand life with its complexities and perfections and which ever way you account for the air that is your breath and the fire of your spirit all stems from the source of life, and the beauty within you is a part of the package. Our beauty is a divine light that sparks through each cell of our being. You truly can never be anything but beautiful, for you are life and life itself is a beauty.
When you understand the source of beauty within you, you then have access to its potential for your greater abundance, power, and ability to manifest change. The power of your beauty is already embedded in your essence, ready to glow. However, it is harnessed through your beliefs about yourself and the actions you take in the name of truth, beauty, and love. You are born with the tools to become a channel for this very compelling and influential vibration. You are the vehicle for this sacred source to shimmer and shine.
"Beauty is the truth, truth beauty. That is all ye know on Earth, and all ye need to know." -John Keats.
We live in a world where our concepts of beauty are decided by the collective consciousness, the standards of our society. Many of us, especially women, are victims of what is known as the 'beauty myth'. The world where fashion rules, perfect body types are most desired and our ways of looking and being are all meant to sell or consume products: beauty products, fragrances, diet pills, hair color, fashion magazines, douches etc. But that is not what true beauty is made of. The truth is we are already whole and complete beings, we are all perfect because we are each perfectly ourselves. What is true is that beauty is everywhere and within everything. For everything on earth and in the universe is the divine source. Unfortunately, many of us were not taught to honor our own beauty in this way. We were warned against being too conceited or told we were not beautiful enough and sadly so many beautiful people have never had their own precious nature reflected back to them. We hide our beauty in the shadows, even the super models complain about places within themselves that they find hideous. In subtle and not so subtle ways we have been disempowered and misdirected by the media to see ourselves as less than the ideal of beauty. Every commercial on television is an assault, telling us what we need to do to be better, happier and more beautiful. This is the beauty myth and it can destroy our sense of self-esteem and even destroy the joy in our lives, it already has for so many people.
As adults, we need to re-teach ourselves where true beauty comes from. We need to re-connect to the radiant source of life within us and teach this to our children. True beauty comes from the heart and soul and spirit of who you truly are, it is your divine right to resonate with self-love and allow your beauty to take the stage. Your authenticity is buzzing with beauty. Life is love, love is truth and truth are beauty. All of life is sacred and all of life is beautiful. Beauty and truth are hands in hand, one does not exist without the other.
Elizabeth Stahl B.A., N.H.C., is the creator and facilitator of "My Goddess Party", Star of Aphrodite Mentoring and Life Coaching, Girls of Power and The Girls and Goddesses Parties – for girls ages 10 and up.
Elizabeth has 16 years of experience in the Natural Health Field specializing in Women's Health and Wellness. She combines her practice as a Natural Health Consultant (NHC), with her Life Coaching practice, Goddess Parties, and Sacred Women's Circles. Elizabeth infuses Girls and Women with the essence of their divine feminine spirit and encourages their growth towards the women they want to be.


I came across the galling handiwork of the cypress twig gall midge fly (Taxodiomyia cupressiananassa) on baldcypress while on a photo-trek in southwest Ohio on Thursday. These spongy, white galls were something of an oddity when I started with Extension 25 years ago. However, for some reason that has changed with these galls becoming a common adornment on baldcypress.


Anti-programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses of patients with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some studies suggested that intra- and inter-tumoral heterogeneity of PD-L1 expression might explain the controversy. This study aimed to analyze the expression of PD-L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph nodes from patients with stage T1-4N+M0 gastric adenocarcinoma to explore the heterogeneity of PD-1 signaling pathway molecules.
In primary tumors and metastatic as well as non-metastatic lymph nodes from patients with stage T1-4N+M0 gastric adenocarcinoma, we detected PD-L1 and PD-L2 expression with immunohistochemistry. CD8(+) T-cell density in primary tumors and PD-1 expression on CD8(+) T cells were detected with immunofluorescence. Univariate analysis was used to determine the prognostic values of them. Cox proportional hazard regression model was used to identify independent risk factors that affect patients' overall survival and disease-free survival.
Among 119 eligible patients who had undergone surgical resection, the positive rate of PD-L1 was higher in metastatic lymph nodes than in primary tumors (45.4% vs. 38.7%, P = 0.005); the positive rate of PD-1 on CD8(+) T cells was significantly higher in primary tumors and metastatic lymph nodes than in tumor-free lymph nodes (both P < 0.001). The intensity of PD-1 expression on CD8(+) T cells in primary tumors and in metastatic lymph nodes were stronger than that in tumor-free lymph nodes from the same patient. Beside, the positive rate of PD-L2 did not show any differences between primary tumors and metastatic lymph nodes. In multivariate analysis, PD-L1 expression, PD-L2 expression, a low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were associated with poor prognosis.
The expression of PD-L1 is heterogeneous in primary tumors and in metastatic lymph nodes from patients with stage T1-4N+M0 gastric adenocarcinoma, which might explain the inconsistent results in assessing the prognostic value of PD-L1 expression in previous studies.
The programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway is important in the negative regulation of cell-mediated immune responses. Immunotherapy targeting the PD-1/PD-L1 axis has great promise in treating many types of cancer and was a breakthrough in cancer treatment. Exploring a molecular biomarker to predict clinical response to anti-PD-1/PD-L1 immunotherapy is thus critically important. However, there is no validated predictive biomarker that can identify patients who would likely respond to anti-PD-1/PD-L1 immunotherapy.
Immune checkpoint molecule PD-1 is expressed by various immune cells, including tumor-infiltrating CD8(+) T cells and CD4(+) T cells, and is activated by its ligands (either PD-L1 or PD-L2). PD-L1 and PD-L2 are expressed by antigen-presenting cells and cancer cells. PD-L1 expression has been detected in cancers of the skin , lung , breast , kidney , bladder , esophagus , stomach , head and neck , among others. PD-L1 expression, assessed with immunohistochemistry, is currently used in clinical trials as one potential biomarker to predict patients' poor prognosis.
Some clinical trials have found that patients with PD-L1-positive tumors had higher rates of response to anti-PD-1/PD-L1 immunotherapy than patients with PD-L1-negative tumors [9–12], and others have found that patients with PD-L1-negative tumors also benefited from anti-PD-1/PD-L1 immunotherapy and that their objective response rate (ORR) was similar to that of patients with PD-L1-positive tumors [13, 14]. Questions arise when using immunohistochemical examination of PD-L1 expression as a companion diagnostic assay for anti-PD-1/PD-L1 immunotherapy. For example, how to determine the threshold that defines positive PD-L1 labeling; what impact the intra- and inter-tumoral heterogeneity of PD-L1 expression might take to the diagnostic assay; how to choose tissue compartment and immune cell population for detection of PD-L1 expression.
Gastric cancer (GC) is the fifth most common cancer globally, with a high incidence in East Asia, especially China [15–17]. Gastric adenocarcinoma is the most common type of GC. Many clinical, molecular, and pathologic data suggest that gastric adenocarcinoma is a heterogeneous disease . Some studies have associated PD-L1 expression with the prognosis of gastric adenocarcinoma [7, 19, 20], although so far, research has focused only on primary tumors. Whether PD-L1 expression in gastric adenocarcinoma differs between primary tumors and metastatic sites is unknown. Moreover, several recent studies of anti-PD-1/PD-L1 antibodies in gastric adenocarcinoma have reported a relatively strong relationship between PD-L1 expression and the rate of response to anti-PD-1/PD-L1 immunotherapy [21–23], which makes it important to identify the exact expression condition of PD-L1 in patients with gastric adenocarcinoma.
We retrospectively detected the expression patterns of PD-L1 and PD-L2 in primary tumors and metastatic lymph nodes, the density of CD8(+) T cells in primary tumors, and the expression of PD-1 on CD8(+) T cells from patients with gastric adenocarcinoma, and determined their associations with clinicopathologic features and patient survival. To make sure the pathologic specimens of the primary tumor, metastatic lymph nodes, and tumor-free lymph nodes were available for every individual patient, we chose patients with stage T1-4N+M0 gastric adenocarcinoma.
Patients with gastric adenocarcinoma who had undergone radical resection in Sun Yat-sen University Cancer Center (SYSUCC, Guangzhou, China) between January 2008 and December 2012 were selected in the study retrospectively. The inclusion criteria were as follows: (1) a diagnosis of gastric adenocarcinoma was confirmed by pathologic analysis; (2) the disease was classified as pathologic T1-4N+M0 cancer according to the 2010 American Joint Commission on Cancer TNM Staging Manual; (3) pathologic specimens were available for the primary tumor, metastatic lymph nodes, and tumor-free lymph nodes; (4) patients had completed at least 4 courses of adjuvant chemotherapy as documented in the medical record; and (5) complete follow-up data were available.
Tissue slides were constructed with materials collected from the Tissue Bank of SYSUCC, and this institution is allowed to perform translational research in compliance with ethical standards and patient confidentiality.
We had obtained consent from all patients to report their individual data. We also had obtained the approval from the Ethical Committee and Institutional Review Board of SYSUCC to conduct the present study.
PD-L1 and PD-L2 expression was detected with immunohistochemistry in both primary tumors and metastatic lymph nodes. All lymph nodes were examined by pathologists after surgeries, and those with cancer cell invasion were conformed as metastatic lymph nodes. All metastatic lymph nodes were numbered and paraffin-embedded. Pathologists chose the metastatic lymph nodes with less necrosis for future detection. Formalin-fixed, paraffin-embedded tissue slides of 3-μm thickness were dewaxed in xylene and rehydrated through graded alcohol. To block endogenous peroxidase, the tissue slides were put in 3% H2O2 for 15 min. Tissue slides were then heated at 100 °C for 25 min in a microwave oven in EDTA (pH 8.0) (ThermoFisher Scientific, Waltham, MA, USA) for antigen retrieval. After cooling to room temperature, slides were incubated with 5% goat serum (ThermoFisher Scientific) for 60 min to prevent non-specific binding. Then, the slides were incubated with the primary antibodies of PD-L1 (E1L3N, 1:100, Cell Signaling Technology, Danvers, MA, USA) and PD-L2 (MAB1224, 1:200, R&D, Minneapolis, MN, USA) overnight at 4 °C. Afterward, the tissue slides were incubated with a goat anti-rabbit secondary antibody (Maixin Biotech, Fuzhou, Fujian, China) for 30 min. Then, 3,3-diaminobenzidine was used for color developing, and hematoxylin for nucleus counterstaining.
The expression of PD-L1 and PD-L2 was scored by two pathologists, both blinded to patients' information. They selected five high-power fields per slide as representatives of the tumor, without known bias, and counted cancer cells with positive staining in these fields. The staining intensity was scored as follows: 0 for no staining, 1 for weak staining, 2 for moderate staining, and 3 for strong staining. The percentage of cancer cells with positive staining was scored as follows: 0%–5% positive staining was scored 0, 6%–25% scored 1, 26%–50% scored 2, 51%–75% scored 3, and 76%–100% scored 4 . The final PD-L1 and PD-L2 expression score was calculated by multiplying the staining intensity score by the percentage score, the product of which ranged from 0 to 12. A receiver operating characteristic (ROC) curve and Youden Index (Youden Index = sensitivity + specificity − 1) were used to determine the optimal cut-off score of PD-L1 and PD-L2 expression. Specimens with an expression score higher than the cut-off were classified as positive; those equal to or lower than the cut-off were classified as negative.
The density of CD8(+) T cells in primary tumors and the expression of PD-1 on CD8(+) T cells in primary tumors, metastatic lymph nodes, and tumor-free lymph nodes were detected with immunofluorescence. The paraffin-embedded tissue slides were dewaxed and rehydrated, and antigen retrieval and non-specific binding prevention were performed as described in the previous subsection. The tissue slides were incubated with the primary antibody of CD8 (ab93278, 1:200, Abcam, Cambridge, Cambridgeshire, UK) and PD-1 (ab52587, 1:200, Abcam) overnight at 4 °C. The secondary antibodies (Alexa Fluor 488 goat anti-rabbit IgG [H + L] and Alexa Fluor 555 goat anti-mouse IgG [H + L], Life Technologies, Los Angeles, CA, USA) were used to bind the primary antibodies for 60 min at room temperature. After counterstaining with 4′,6-diamidino-2-phenylindole (DAPI) (P36931, Life technologies) for 5 min, the slides were observed under a confocal laser scanning microscope (OLYMPUS FV1000, OLYMPUS, Tokyo, Japan).
The density of CD8(+) T cells in primary tumors was scored as follows: 0 for no CD8(+) T-cell infiltration, 1 for focal infiltration with mostly perivascular distribution in tumor, 2 for moderate infiltration with prominent distribution among tumor cells, and 3 for severe infiltration with diffused distribution in tumor . Scores of 2 and 3 were considered to indicate a high density of CD8(+) T cells infiltrating the tumor, whereas scores of 0 and 1 indicated a low density.
PD-1 expression on CD8(+) T cells was evaluated with fluorescence intensity as well as the percentage of CD8(+) T cells with positive PD-1 staining. The fluorescence intensity was scored from 0 to 3 for none, weak, moderate, and strong staining, respectively. The percentage of positive CD8(+) T cells was scored from 0 to 4 for 0%–5%, 6%–25%, 26%–50%, 50%–75%, and 76%–100% positive staining, respectively. The product of the two scores determined the final score of PD-1 expression, which ranged from 0 to 12. ROC and Youden Index were also used for PD-1 expression classification.
The follow-up information was obtained from the Department of Follow-up at SYSUCC. The patients were followed via telephone every month. The final date of follow-up was June 30th, 2016.
The associations between PD-L1 and PD-L2 expression in primary tumors and metastatic lymph nodes, the density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells and clinicopathologic characteristics were evaluated with χ2 tests. Correlations between PD-L1, PD-L2, PD-1 expression and CD8(+) T-cell density were analyzed with the Kendall's tau-b test. Overall survival (OS) was calculated from the date of diagnosis to the date of death. Disease-free survival was calculated from the date of diagnosis to the date of relapse. OS and DFS were analyzed with Kaplan–Meier curves. Patients alive at the end of the study were censored at the last follow-up. Variables with P values less than 0.05 in the univariate analysis were included in the Cox proportional hazards regression model for multivariate analysis.
All data were analyzed with the IBM SPSS Statistics 21 software (SPSS Inc., Chicago, IL, USA). Alpha was set at 0.05, and all tests were two-tailed.
A total of 119 patients were eligible, with a median age of 55 years (range 25–66 years). The median number of courses of adjuvant chemotherapy was 6 (range 4–12). 85 patients were treated with the capecitabine–oxaliplatin or the leucovorin–fluorouraci–oxaliplatin regimen. The median follow-up was 28.0 months (range 4.5–92.0 months). As of the last follow-up visit, the cancer had progressed in 86 patients and was the cause of death in 80 patients.
The areas under the ROC curves of PD-L1, PD-L2, and PD-1 expression were 0.652 [95% confidence interval (CI) 0.550–0.754, P = 0.007], 0.671 (95% CI 0.571–0.771, P = 0.003), and 0.627 (95% CI 0.527–0.726, P = 0.025), respectively (Fig. 1). A PD-L1 expression score of 4 maximized the Youden Index 0.163 as the optimal cut-off score. A PD-L2 expression score of 6 maximized the Youden Index 0.259 as the optimal cut-off score. A PD-1 expression score of 4 maximized the Youden Index 0.203 as the optimal cut-off score.
PD-L1 was expressed predominantly in the cytoplasm and on the membrane of tumor cells (Fig. 2a–d). The positive rates of PD-L1 in both primary tumors and metastatic lymph nodes were significantly associated with Lauren classification and vascular invasion (all P < 0.05; Table 1). PD-L1 expression was inconsistent in primary tumors and metastatic lymph nodes in individual patients (Fig. 3). The positive rate of PD-L1 was significantly higher in metastatic lymph nodes than in primary tumors (45.4% vs. 38.7%, P = 0.005).
PD-L2 was also expressed predominantly in the cytoplasm and on the membrane of tumor cells (Fig. 2e–h). The positive rates of PD-L2 in both primary tumors and metastatic lymph nodes were associated with vascular invasion and neural invasion, and that in metastatic lymph nodes was associated with Lauren classification (all P < 0.05; Table 1). The positive rate of PD-L2 was not significantly different in primary tumors and metastatic lymph nodes (28.6% vs. 26.9%, P > 0.05).
The density of CD8(+) T cells in primary tumors was higher in non-intestinal type than in intestinal type gastric adenocarcinoma (P = 0.011). Stage IIIB–IIIC tumors exhibited a lower CD8(+) T-cell density than stage II–IIIA tumors (P = 0.018). The density of CD8(+) T cells in primary tumors was not associated with vascular invasion or neural invasion (Table 2).
PD-1 was expressed predominantly on the membrane of tumor cells (Fig. 4). The positive rates of PD-1 expression on CD8(+) T cells were 37.8% in primary tumors, 39.5% in metastatic lymph nodes, and 10.9% in tumor-free lymph nodes. PD-1 expression on CD8(+) T cells in primary tumors was not associated with any clinicopathologic factors (Table 2). The intensity of PD-1 expression on CD8(+) T cells in primary tumors and in metastatic lymph nodes were stronger than that in tumor-free lymph nodes from the same patient (Fig. 5).
PD-L1 expression was associated with PD-L2 expression in both primary tumors (P = 0.043) and metastatic lymph nodes (P = 0.012). In primary tumors, the density of CD8(+) T cells was associated with PD-L1 expression (P = 0.022) and PD-L2 expression (P = 0.004). Neither PD-L1 nor PD-L2 expression was associated with PD-1 expression on CD8(+) T cells in primary tumors (both P > 0.05; Table 3). In metastatic lymph nodes, both PD-L1 expression (P = 0.034) and PD-L2 expression (P = 0.002) were associated with PD-1 expression on CD8(+) T cells (Table 4).
Patients with PD-L1 expression in primary tumors had lower 5-year OS and DFS rates than patients without PD-L1 expression (OS: 15.2% vs. 43.8%, P = 0.001, Fig. 6a; DFS: 10.9% vs. 38.4%, P = 0.002, Fig. 6b). Also, patients with PD-L1 expression in metastatic lymph nodes had lower 5-year OS and DFS rates than patients without PD-L1 expression (OS: 14.8% vs. 47.7%, P < 0.001; Fig. 6c; DFS: 13.0% vs. 40.0%, P = 0.004, Fig. 6d).
Patients with PD-L2 expression in primary tumors had lower 5-year OS and DFS rates than patients without PD-L2 expression (OS: 11.8% vs. 41.2%, P = 0.008, Fig. 6e; DFS: 8.8% vs. 35.3%, P = 0.007, Fig. 6f). Patients with PD-L2 expression in metastatic lymph nodes also had lower 5-year OS and DFS rates than patients without PD-L2 expression (OS: 9.4% vs. 41.4%, P < 0.001, Fig. 6g; DFS: 9.4% vs. 34.5%, P < 0.001, Fig. 6h).
Patients with PD-1 expression on CD8(+) T cells in primary tumors had lower 5-year OS and DFS rates than patients without PD-1 expression (OS: 17.0% vs. 43.1%, P < 0.001, Fig. 6i; DFS: 11.1% vs. 37.8%, P = 0.002, Fig. 6j). Patients with PD-1 expression in CD8(+) T cells in metastatic lymph nodes had lower 5-year OS and DFS rates than patients without PD-1 expression (OS: 17.0% vs. 43.1%, P = 0.007, Fig. 6k; DFS: 14.9% vs. 36.1%, P = 0.021, Fig. 6l).
Patients with a high density of CD8(+) T cells in primary tumors had higher 5-year OS and DFS rates than patients with a low density of CD8(+) T cells (OS: 39.7% vs. 21.7%, P = 0.007, Fig. 6m; DFS: 34.2% vs. 17.4%, P = 0.010, Fig. 6n).
When patients were allocated into four groups based on different combinations of PD-L1 expression in tumor cells and PD-1 expression on CD8(+) T cells in primary tumors, patients without PD-L1 and PD-1 expression had the best prognosis (Fig. 6o, p).
In multivariate analysis, PD-L1 expression in primary tumors, PD-L2 expression in metastatic lymph nodes, a high density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were independent prognostic factors for shorter DFS; PD-L1 expression in metastatic lymph nodes, PD-L2 expression in primary tumors, a high density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were independent prognostic factors for shorter OS. Besides, stage T3–T4 and tumor location were independent prognostic factors for shorter OS and DFS; neural invasion was an independent prognostic factor for shorter OS (Table 5).
We evaluated the expression of immune checkpoint molecules PD-L1 and PD-L2 in tumor cells, as well as the density of CD8(+) T cells and PD-1 expression on CD8(+) T cells in patients with T1-4N+M0 gastric adenocarcinoma. PD-L1, PD-L2, and PD-1 expression and a low density of CD8(+) T cells in primary tumors were associated with a poor prognosis.
The positive rate and prognostic value of PD-L1 expression in GC has been inconsistent. In one study that involved 102 patients with gastric adenocarcinoma in China, the positive rate of PD-L1 was 42.2% , which was slightly higher than that in our study. The difference in criteria to evaluate PD-L1 expression might account for the inconsistency. Besides, both studies found that PD-L1 expression in primary tumors was associated with vascular invasion and was an independent risk factor of prognosis. A study in Korea reported that PD-L1 expression was associated with vascular invasion and Lauren classification of gastric adenocarcinoma and was an independent risk factor of poor prognosis for patients with a high density of CD8(+) T cells in primary tumors , which were consistent with the results of our study. One study in USA also reported that PD-L1 expression in tumor cells from primary tumors was associated with poor prognosis of patients with gastric adenocarcinoma, but the positive rate of PD-L1 was only 12% , which was significantly lower than data from Asia studies [25, 26]. Although most studies showed that PD-L1 expression was associated with poor prognosis of GC, a Japanese study including 243 patients with curatively resected GC found that both PFS and OS were longer in PD-L1-positive patients than in PD-L1-negative patients . It is possible that the difference in patients' races might be related to the inconsistency.
The relationship between PD-L1 expression and patients' response rate to anti-PD-1/PD-L1 immunotherapy was also not clear . In the phase 1b KEYNOTE-012 study of 39 patients, pembrolizumab showed promising antitumor effect on PD-L1-positive, recurrent or metastatic gastric adenocarcinoma, with an ORR of 22% and a median OS of 11.4 months among these patients . The prognostic and predictive values of PD-L1 expression in gastric adenocarcinoma patients who underwent anti-PD-1/PD-L1 immunotherapy thus remain to be explored. The inconsistent results from different studies might be explained by the different antibodies and specimens (frozen vs. paraffin-embedded tissues) used for detection . In our study, we chose a commonly used, commercially available antibody E1L3N clone to detect PD-L1 expression. Besides the E1L3N clone, several other antibodies for PD-L1 expression detection are also used in clinical practice, including 9A11 (general usage), Ventana SP142 (for patients treated with atezolizumab), Ventana SP263 (for patients treated with durvalumab), Dako 22C3 (for patients treated with pembrolizumab), and Dako 28-8 (for patients treated with nivolumab). In a study assessing these six antibodies for the detection of PD-L1 expression with microarray immunofluorescent staining, concordance among four antibodies (SP142, E1L3N, 9A11, and SP263) revealed regression of tumor tissue cores (R 2 = 0.42–0.91) and cell line cores (R 2 = 0.83–0.97) . All six antibodies had high levels of concordance (R 2 = 0.76–0.99) when using chromogenic staining in isogenic cell lines. A phase I trial involving 39 non-small cell lung cancer (NSCLC) patients compared four anti-PD-L1 antibodies (Dako 22C3, Dako 28-8, Ventana SP142, and Ventana SP263) using the Blueprint PD-L1 IHC Assay and demonstrated that the percentage of PD-L1-positive tumor cells was comparable when the 22C3, 28-8, and SP263 clones were used, whereas fewer tumor cells were stained with the SP142 clone . Based on results from previous studies, the results of PD-L1 expression detected with the E1L3N clone in the present study was reliable and comparable with those of other studies.
Because PD-L1 expression can also be detected in stromal cells, the cell types chosen to detect PD-L1 expression might also influence the results . We only detected PD-L1 expression in tumor cells in five high-power fields per slide which were selected without known bias to avoid influence caused by cell type.
We found significant heterogeneity of PD-L1 expression between primary tumors and metastatic lymph nodes. The abundant immune cytokines in the microenvironment of metastatic lymph nodes can induce PD-L1 expression, which might explain the increased positive rate of PD-L1 expression in metastatic lymph nodes than in primary tumors. However, some cases showed PD-L1 expression in the primary tumor, but not in metastatic lymph nodes. The heterogeneity of PD-L1 expression is probably responsible for the inaccuracy of using PD-L1 as a predictor of response to anti-PD-1/PD-L1 immunotherapy in current clinical trials. Sunshine and Taube  reported that patients with PD-L1 expression in pre-treatment specimens of primary tumors were more likely to respond to anti-PD-1/PD-L1 immunotherapy than those without PD-L1 expression. However, objective response was also observed in patients without PD-L1 expression, although with a relatively low rate . Further exploration in one patient with several pre-treatment specimens found heterogeneous PD-L1 expression in the primary tumor, the metastatic lymph node, and subsequent subcutaneous metastases . Thus, if PD-L1 expression status is detected in only one specimen, false negative results might reduce the efficiency of using PD-L1 as a predictor of response to anti-PD-1/PD-L1 immunotherapy.
Few studies have evaluated the expression and function of PD-L2 in patients with gastric adenocarcinoma. One study of anti-PD-1 immunotherapy for 41 patients with various cancer types reported that PD-L2 expression was detected in 8 patients with renal cell carcinoma, melanoma, or NSCLC . Another study found a 51.7% rate of PD-L2 expression in patients with esophageal adenocarcinoma . In our study, PD-L2 was expressed in 28.6% of patients with gastric adenocarcinoma and predicted short OS in those patients. As in another study, PD-L2 expression was positively correlated with PD-L1 expression in gastric adenocarcinoma, indicating a possible interaction between the two molecules .
The density of CD8(+) T cells in primary tumors has been reported to predict prognosis in various types of cancer [33–37]. In the present study, we found no difference in the positive rate of PD-L1 between patients with high and low CD8(+) T-cell density in primary tumors, in contrast to a USA study reporting that a high density of CD8(+) T cells was associated with a high positive rate of PD-L1 expression in gastric adenocarcinoma . However, an Asian study on gastric adenocarcinoma also found no association between immunosuppressive proteins, such as PD-L1, cytotoxic T-lymphocyte-associated protein 4, and indoleamine 2,3-dioxygenase, and infiltration density of immune cells, including CD3(+), CD4(+), CD8(+), and PD-1(+) cells, in the tumor microenvironment . This discrepancy might be explained by the mechanisms of PD-L1 overexpression in tumor cells and by the difference in signatures of tumor immunity between Asian and non-Asian patients with gastric adenocarcinoma. On one hand, PD-L1 could be up-regulated by both intrinsic aberrant pathways involved in carcinogenesis and extrinsic cytokines produced by other stromal cells in the tumor microenvironment [38–40]. On the other hand, the density of tumor-infiltrating T cells was lower in Asian patients with gastric adenocarcinoma than non-Asian patients as reported in a previous study , revealing a large distinction in the immune status of tumor environment in patients from different geographic areas. Besides, different characteristics of gastric adenocarcinoma between Asian and non-Asian populations might also be associated with the difference in median age of patients. The median age of patients in our study was 55 years old, which is consistent with the data reported by other studies in China [25, 42]. However, in the USA study, the median age of patients was 67 years old .
PD-1 is important in inhibiting the function of T cells by tumor cells through the PD-1/PD-L1 pathway , and it is a significant prognostic factor in several types of cancer [44–47]. PD-1 can be expressed on various types of activated T cells, and its function might be different . The prognostic values of PD-1 expression on T cells were inconsistent among different studies [20, 46–48]. In the present study, we analyzed PD-1 expression on CD8(+) T cells and found it to be a unfavorable prognostic factor in gastric adenocarcinoma. The clinical value of PD-1 expression on other types of immune cells needs to be explored in further studies.
There were some limitations in the present study. First, we only analyzed the density of tumor-infiltrating CD8(+) T cells, but did not analyze the densities of CD3(+) T cells and CD4(+) T cells, which may also have prognostic values in GC patients. Second, the heterogeneity of PD-L1 expression was analyzed by comparing primary tumors with metastatic lymph nodes. If distant metastasis tissues could be obtained to detect PD-L1 expression, the heterogeneity analysis could be improved.
In conclusion, PD-L1 and PD-L2 expression in primary tumors and matched metastatic lymph nodes, low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were unfavorable prognostic factors in patients with stage II/III gastric adenocarcinoma. PD-L1 expression was associated with PD-L2 expression as well as the density of CD8(+) T cells in primary tumors. PD-L1 expression in primary tumors was not consistent with that in metastatic lymph nodes. We suggest assessing multiple specimens when determining the status of PD-L1 expression in GC.
YG, SXC, JS collected patients' information. YG and DZX wrote the manuscript. YG, KFW, BYC finished immunohistochemistry. YG and YCC finished immunofluorescence. XKZ and colleagues scored the staining of slides. SL, WQJ guided experiments operating. Design of experiments was accomplished by MHH and FHW. All authors read and approved the final manuscript.
The key raw data have been deposited into the Research Data Deposit (http://www.researchdata.org.cn), with the Approval Number of RDDB2017000071.
GLOBOCAN 2012. Estimated cancer incidence, mortality and prevalence worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed 24 July 2017.


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Home on Anna Maria Island by Elley Arden Release Day Blitz
Pittsburgh Privateers third baseman Gavin Sullivan is home on Anna Maria Island with a lot on his mind: his mother's recent battle with breast cancer and, now, the surprising news his oldest brother, Colby, is a twin. Gavin has a sister he's never met, and worse, he's sworn to secrecy while his parents try to find her. Is it any wonder he shows up to Spring Training thirty pounds heavier than last season? Armed with a complicated diet and a warning from Coach Zee, Gavin feels wrecked, until he finds a half-naked goddess on his parent's stretch of beach. Funny how the body that has been making him feel so miserable lately suddenly has him flying high.
Curve model Emerson Raye wants to prove the naysayers back home in West Virginia wrong. Big is beautiful, too. All she has to do is land a spot in the Sports Unlimited Swimsuit Edition by convincing America to vote for her. When pro athlete Gavin Sullivan stumbles onto her oceanfront photo shoot and asks her out for drinks, Emerson and her assistant concoct a plan to leak photos of the date to the media and create the vote-getting buzz Emerson needs. Soon, Emerson realizes there's more to Gavin than meets the eye, and their temporary, no-strings relationship heats up. But can something lasting survive under harsh media scrutiny when secrets threaten to sabotage everything?
Emerson had been kissed before. She had a modelling career full of air kisses, double-cheek kisses, and the occasional, friendly smooch on the mouth. She also had a personal life spattered with overeager, often rushed kisses that were nothing more than prerequisites for the main event.
Gavin Sullivan's kisses weren't like anything she'd ever encountered.
He took his time, eliciting pleasure with more than his mouth. His hands grazed her neck, his thumbs stroked her jaw. His fingers threaded through the fine hairs at her nape. And all along, his mouth explored her mouth. Lips to lips. Tongue to tongue.
He tasted like butter and sweet champagne. He smelled like citrus fruit and sandalwood.
She leaned into him and whimpered. Her hands gripping the collar of his linen shirt. Her body burned. Her brain urged her to crawl into his lap and settle in for a long, slow, mind-blowing ride. And she was seconds away from obeying when above them, someone cleared his throat.
"Sorry for the interruption."
Emerson jerked back.
"Dessert?" the man asked as he set shell-shaped bowls of sorbet in front of them.
Gavin didn't move. He didn't take his hungry eyes off Emerson. "Thank you," he said to the man. "That'll be all for tonight."
Looking into Gavin's eyes, Emerson's heartrate tripled. She wanted him. Even if it made her vulnerable. She wanted this. Even if it was a fantasy.
When the man left, Gavin grinned and reached for the silver spoon beside her bowl. "Dessert?" He dipped the spoon into the single scoop of light-colored sorbet and lifted it like he might feed her, but then, with an even brighter grin, he brought the spoon to his own beautiful mouth and licked it clean. "Lemon," he said, his voice warm and deep.
She opened her mouth, and, for a split second, was afraid her throat was too dry to speak. "I like lemon," she said, watching him help himself to another bite.
This time, he set the spoon down, and inched closer, so close, she could feel the cold on his tongue and smell the lemon on his lips.
"Want a taste?" he whispered.
She wrapped her arms around his powerful shoulders and pulled him in. Their lips locked. Their tongues tangled. He shoved his hands beneath her thighs and guided her onto his lap. Skirt riding high. Heart beating fast. She settled over his erection, biting back a moan as he nipped at her jaw and rubbed erotic patterns up and down her back. And then, he was licking her ear, tugging her lobe, sliding his hands along the silk of her dress to her stomach and the underside of her breasts.
Emerson tipped back her head, and her eyes fluttered open to the starry sky. Was it awful to pray during something like this? Because she wanted to. She wanted to pray for this to be real.
Elley Arden is the author of the groundbreaking and critically acclaimed Cleveland Clash series. She previously worked for The Walt Disney Company and spent over a decade as a non-fiction writer and editor. When she's not writing, Elley can be found reading, watching sports, redecorating her house, or kicking her husband's butt in Words With Friends. She lives in Pennsylvania with her high school sweetheart and their three crazy (in a good way) kids.