text:
Capaldi new patron of cancer charity
This news post is about 7 years old
The Doctor backs Scottish cancer retreat
4th May 2015 by Susan Smith
Peter Capaldi becomes patron of cancer charity
Doctor Who actor Peter Capaldi is the new patron of It's Good 2 Give.
The Scot will help to promote the cancer charity to raise much needed funds for children affected by the disease.
Capaldi was introduced to 16-year-old Millie McLean by a relative while the Edinburgh schoolgirl was being treated for a rare form of cancer and they remained in contact until she passed away last month.
The actor said: "I was introduced to It's Good 2 Give after the charity had helped a family I know. I was hugely impressed by their approach and ambition.
"By spreading the word I hope to help them raise the funds they need. It really is Good 2 Give; please help them by giving what you can."
The charity was established by Lynne McNicoll in 2010. Its latest campaign is to build a luxury residential home on the banks of Loch Venachar near Callander that can be used by families for breaks during treatment.
McNicoll said: "You can't imagine how excited we are to have the support of Peter. We are at a critical stage in our fundraising and desperately need to reach out to people who are keen to support everyday families who are battling with the emotional and physical challenges of caring for a child who is seriously ill.
"Our help is every day, a little and often approach. But next year, while we will continue to do this, we are also going to be able to offer families the Ripple Retreat, a fabulous exceptional designer house built on the shores of Loch Venachar.
"From a standing start, we have raised £750,000 but we need much more to cover the costs of the build and to fit out the house to the high standards we want.
"Our £1 million target is the reason we will launch the Ripple Retreat Appeal in January."
Stars out in force for charity sci-fi con 2021
Campaign calls for support for international volunteers


text:
Ed Boon: Mortal Kombat can deliver a "radical experience" on next generation consoles
"Finish him" on a new console.
In terms of sales and critical acclaim, Mortal Kombat 9 (MK9) was a huge success. The game returned to its roots by reintroducing the original cast like Street Fighter IV did and the results show. While it may not be a hit with the fighting game community (FGC), numbers don't lie.
With his no nonsense attitude, it should come as no surprise that Ed Boon wants the next entry in the MK series to feel larger than life. He tells CVG, it may need to be done on an Xbox 720, PS4, and Wii U.
"If you introduce another edition of your game on the same console, you cannot provide a radically different experience. I'm sure, if we were to do a new Mortal Kombat game on next generation systems, I think we would be able to provide dramatically different experiences."
Fernando's POV: While the Xbox 360 and PS3 are aging, people aren't showing signs that they want to spend a lot of money on next generation consoles. I'm sure where the next Mortal Kombat game ends up will depend on the success of these new consoles, starting with the Wii U.
Labels: Ed Boon, Mortal Kombat, NetherRealm, PS4, WB Games, Wii U, Xbox

redpajama_set_name: RedPajamaCommonCrawl


text:
Dev Blog 19th May 2017
I previously mentioned our efforts to get the game server running in Docker. We've pretty much cracked that problem, and already have a couple of experimental servers running in regions we previously couldn't support. We're investigating further deployment locations. For those interested, we've added some information on our server setup page: http://supraball.net/server-support#linux
For brand new players, we've added a little "Welcome to Supraball" page the first time the game starts up, giving one-click access to either the tutorial or a botmatch. Eventually this will morph into a quick-start guide to the launcher, but until the launcher design stabilises, anything more now would be wasted effort.
We've done a little tidy up of the launcher main page, mostly making a couple of things optional, and removing some redundant buttons. We have a bigger one planned for post F2P. There's been a few rumbles of dissatisfaction in the community about the launcher recently. We know the launcher rubs a few people the wrong way, but it continues to be necessary as long as the main game is written using UDK.
The backer shop is looking nice and will be ready very soon. Backers will get an email containing a link to a special webpage we've set up. All you'll need to do is log in and we will link any rewards you claim to your steam account.
We've also got an update coming soon, most likely early next week. The main new feature is item chests and keys. We'd hoped to have it out this week, but internal beta testing highlighted a few bugs which we are fixing at the moment. After that, there will likely be one further update before we switch to F2P.
There are currently six things left to do on the must-have list before we can do the F2P release. This is mostly back-end and operations stuff. e.g. Load test the master server, deploying enough servers in enough locations for everyone.
There are also ten items on the nice-to-have list. These are things we'd like to get done but time and budget is working against us. This includes features such as an in-game taunt wheel, and item crafting (i.e. exchanging common items for a rare one).
We're looking forward to the F2P release with a mixture of nerves and excitement, both of which will no doubt grow as we get closer to the event. It's another big opportunity to get in front of a wider audience and we hope that audience loves the game as much as we all do.


text:
/*
 * To change this license header, choose License Headers in Project Properties.
 * To change this template file, choose Tools | Templates
 * and open the template in the editor.
 */

package com.web.mavenproject6.validators;

import com.web.mavenproject6.validators.annotation.MyEmpty;
import javax.validation.ConstraintValidator;
import javax.validation.ConstraintValidatorContext;

/**
 *
 * @author Aleks
 */
public class MyEmptyValidator implements ConstraintValidator<MyEmpty, String>  {

    private int max = 0;
    private int min = 0;

    @Override
    public void initialize(MyEmpty a) {
      this.max = a.max();
      this.min = a.min();
    }

    @Override
    public boolean isValid(String t, ConstraintValidatorContext cvc) {
        System.out.print("we are here!");
        return (t != null && !t.isEmpty())&&(t.length()>=min&&t.length()<max);
    }

}

redpajama_set_name: RedPajamaGithub


You'll arrive in Queenstown, the heart of adventure in New Zealand. Collect your rental car at the airport and head to your central Queenstown accommodation, where you'll be perfectly situated to experience the best of the town.
With a vibrant downtown packed with fine restaurants and bars, and a lakeside promenade that's perfect for watching the sunset or catching a sightseeing boat, you'll never run out of things to do. And that's before you even start your Queenstown skiing adventure!
Stay 5 nights in Queenstown.
Once you've settled into Queenstown, it's time to hit the slopes!
After conquering the mountain, experience Queenstown's nightlife with Après-ski at one of Queenstown's high-energy bars or restaurants.
Let your muscles rejuvenate with a day of relaxation or exploration. Known as the adventure capital of New Zealand, Queenstown offers every extreme activity imaginable. Push yourself to the limits with skydiving, jet boating, and bungy jumping, or choose from something a bit more peaceful. You can take in the beauty of the region with activities like cruises on the TSS Earnslaw (fine dining included!), scenic helicopter flights, wine tours, and backcountry safaris.
We can help you add Queenstown activities to your ski package; ask for suggestions, or tell us what you want to check off your bucket list!
Fire up those ski legs and head up the mountain for a great day of fun at The Remarkables or Coronet Peak.
Return your rental car at the Queenstown Airport and leave beautiful Queenstown at your leisure.


text:
Universal Import & Export Ltd
Family-Run Import-Export Business Thrives Through Diversification
Founded in Malta in 1972 by Gul Mohnani, Universal Import & Export Ltd was created to import textiles and textile-related machinery to serve the local market. As the local market grew, so too did Universal, becoming the industry's leader within five years supplying everything from needles to machines and from sewing threads to fabrics. Ultimately, it opened a retail outlet, showroom and office building.
Universal Import & Export Limited
3.4m Euros (2018)
Sage Pastel Evolution
OTHER SOLUTIONS CONSIDERED
TradeGecko, BrightPearl
Softype
Learn How A Unified Commerce Platform Enables Great Customer Experiences.
"Our company has grown in an average of about 10 percent per year since we implemented NetSuite in 2015. It's really been a big benefit for us to become more lean with our purchasing. The real-time reporting, not only for inventory, makes decision-making a whole lot easier!" Stefan Mohnani, Director, Universal Import & Export Ltd
Shifting Market Creates New Opportunities
Success through adaptation
As the textile industry slowed and businesses moved abroad seeking cheaper labor, Universal had to adapt and diversify. The company began importing packaging and labeling consumables and machines, and gradually adding adhesives, health and safety, and electronic and scientific products widening its target market to span multiple industries, whilst maintaining its focus on serving industrial manufacturing B2B customers.
Adding manufacturing, services pays off
To further diversify, Universal added light manufacturing for the medical industry and a services arm that provides technical support for the machinery in all the industries the business serves. Although the main customer base is in the Maltese islands, the company now ships overseas, operating from a 1,000-square-meter warehouse supported in part by a 3PL provider.
Looking to the cloud
As Universal grew and diversified, its existing Sage system for managing the company began to buckle under the strain and as the server that ran the on-premise system aged, the company elected to implement NetSuite over TradeGecko and BrightPearl as a modern, comprehensive, cloud-based system.
Second generation success
The family-owned business, now in its second generation, can continue to expand and diversify with NetSuite managing its financials, inventory and customer records. Management will also be introducing an ecommerce channel with NetSuite SuiteCommerce.


Home » Blog » Rare Pink are Pitch to Rich Semi-Finalists!
From 524 entrants within the 'Grow' category, we have made the top 10 of the Virgin Media Business Pitch to Rich competition!
Thanks to your support, we made the shortlist where we were chosen as semi-finalists.
Now we need you to vote to get us to the live final and a chance to win £250,000.
Previous votes are no longer counted so even if you voted last time, please vote again!
We need to reach the top 3 to attend the live finals on the 26th of June where we can pitch our business directly to Richard Branson and his team of prestigious judges including Jo Malone, David Gandy, Jon Oringer and Justine Roberts.
Show your support for Rare Pink by voting here.
Voting closes June 16th so please vote now!


"THE PINK HOUSE; THE LEGENDARY RESIDENCE OF EDWIN BRADFORD HALL AND HIS SUCCEDING GENERATIONS IN WELLSVILLE, NEW YORK"
"The story of Allegany County (N.Y.) is the best kind of story—with a cast of characters any talented writer would struggle to imagine. Medicine men, dance hall girls, missionaries, and industrialists all have written on the pages of our past. Their lives and livelihoods have shaped the course of our communities and continue to speak into our future though at times only through a whisper.
One of the primary goals of ACHS and this website is to provide support for all of Allegany County Local Historical Societies and Museums as a "ring of history". We attempt to publish MEETINGS & PROGRAMS of these organizations when the material is provided to us.
Navigational Guide Map of Website; Offers quick links. This is a good place to start exploring our site.
Also, the left margin Menu Items and the right margin Towns & Villages Items will assist in navigating to specific articles about the various sections of the website.


Having a positive and progressive attitude to customer's fascination, our organization constantly improves our solution high-quality to fulfill the requirements of shoppers and further focuses on safety, reliability, environmental prerequisites, and innovation of Car Usb Flash Drive , Card Usb Flash Drive , Cheap Usb Flash Drive , Our Organization Core Principle: The prestige very first ;The quality guarantee ;The customer are supreme.
Sticking to the principle of "Super High-quality, Satisfactory service" ,We are striving to generally be a very good business partner of you for Car Usb Flash Drive , Card Usb Flash Drive , Cheap Usb Flash Drive , We adopt advanced production equipment and technology and perfect testing equipment and methods to ensure our product quality. With our high-level talents scientific management excellent teams and attentive service our goods are favored by domestic and foreign customers. With your support we are going to build a better tomorrow!


text:
Jeremy Hill Done For Season with Torn ACL
by Ian Glendon
in AFC, AFC East, Featured, NFL, NFL Featured
The New England Patriots picked up their first win of the season yesterday at Gillette, however, they suffered their first major in-season injury. According to reports, running back Jeremy Hill suffered a torn ACL and will miss the entire season. Hill was beginning his first season in New England.
From The Aftermath: #Patriots RB Jeremy Hill had made the most of his fresh start in New England, earning a key role in the offense. Now, he's out for the season with a torn ACL. pic.twitter.com/NH9UkXJEhY
— Ian Rapoport (@RapSheet) September 10, 2018
It was an unfortunate diagnosis but expected after the obvious pain Hill was in on the field following an accidental hit from teammate James Develin. The injury occurred just after halftime when Hill was trying to make a tackle on a Tom Brady interception.
Latest Patriots News
It Was a Season of Comebacks For NFL 2021
Patriots' Isaiah Wynn Will Miss Wild Card Game Against Bills
Patriots Enemy Profile: Buffalo Bills Wild Card Round
Hall Finalist Willie Anderson: Why I Think Corey Dillon is "One Of The All-Time Greatest Backs"
AFC Wild Card Weekend Storylines
Hill was carving out a nice niche for himself after a strong preseason won him the job over Mike Gillislee. Hill's play was even more important with the absence of rookie Sony Michel. Now, Michel's health becomes more of a focus as the running back depth is down to James White, Rex Burkhead, and Devlin. Michel hasn't seen much time throughout the preseason but the talent is there. It would certainly soften the impact from losing Hill for the remaining 15 games and into the playoffs.
– Ian Glendon is the Editor-In-Chief of Full Press Coverage. He covers the NFL. Like and follow on Follow @iglen31 Follow @FPC_Patriots and Facebook.
Tags: Jeremy HillNew England PatriotsSony Michel
Emmanuel Ogbah Dealing With Sprained Ankle
Jaguars vs. Giants: The Good, The Bad, and The Ugly
Ian Glendon
I am the Founder and Editor-In-Chief of Full Press Coverage. I have covered High School baseball in the Tampa Bay region in addition to the New England Patriots, NHL, and now the Tampa Bay Buccaneers.


1435 10th Street has a Walk Score of 66 out of 100. This location is Somewhat Walkable so some errands can be accomplished on foot.
This location is in the Uptown Moline neighborhood in Moline. Nearby parks include Stephens Park, Velie Park and Karstens Park.
Explore how far you can travel by car, bus, bike and foot from 1435 10th Street.
1435 10th Street has some transit which means a few nearby public transportation options.
1435 10th Street is in the Uptown Moline neighborhood. Uptown Moline is the 3rd most walkable neighborhood in Moline with a neighborhood Walk Score of 68.


Alright, it's that time of the year! With both the Niagara Meet, and CVC Ilderton Show behind us. Looking forward to this one again.
Last year's was great, we had a great turnout at the Volvo of Canada Headquarters with over 30 cars ranging from an old 142, 242 GT, 850s, P1s S40/C30/V50, Rs all the way up to the all new 2011 S60! We had prizes and sponsors, and we definitely had a good time.
Without further adieu, here is the proposed date and time. Location is still being considered, as you may recall, Volvo HQ did not allow us to meet there, but we did it anyway. We were offered to host it at Robert's Volvo after the meet and that they would sponsor the lot, but we're still considering going back to Volvo HQ for it (due to the spaces and how nice it is over there). Any other ideas or should we be rebel and just go anyway?
People are welcome to join at any time, but the meet starts officially at 1:30pm. The event won't have an official end time but rather until everyone starts to slowly disperse.
Feel free to bring friends, family, and most importantly cameras.
As well, if you have parts for sale, I suggest you should bring them! Don't be shy about your car, if it's stock, it's fine! Needs work? Perfect time to come and ask some experts or enthusiasts that have a similar car. There's no excuse to miss this!
This page will be updated as more sponsors, prizes, and attendees signup!
Last edited by Devolv; 08-15-2011 at 12:22 PM.
When is the next GTA meet?


Click here to complete the online electronic account application with a digital signature. Be sure to enter DeCarley Trading as your broker!
Thanks for choosing DeCarley! We are confident that DeCarley is capable of exceeding your expectations of a brokerage firm at competitive rates and look forward to working with you.


text:
The Garfield Political
Oprah Running for President is a Bad Idea
Oprah Winfrey gave a really good speech at the Golden Globes last night. Halfway through, I was expecting her to announce she was running for president. And that would have been a bad thing. It still would be.
When Trump announced he was running for president, pretty much everyone who didn't support him railed against his lack of experience, how he was trying to become a celebrity president. Well, he won and became one. And has so far proved everyone right. Celebrities can't govern.
I don't care that Oprah is liberal (and I'm not 100% sure how she stands on all the issues, because she's not really out there on everything). Celebrities should never again be given a fair shot at becoming president. Let's look at why:
In 2016, Democrats lost the higher ground on multiple issues because they ended up becoming hypocritical on them, primarily how Hillary Clinton argued that women should support her because Trump was accused of sexually harassing and assaulting women. That argument was destroyed because of Bill Clinton being accused of the same things.
The best hope for Democrats in 2020 is to show how Trump has failed at governing. We need to show the Trump voters who chose him because he was going to pull them out of poverty that he actually caused more jobs to move abroad. We need to show the Trump voters who chose him because they were mad about Hillary's emails that Trump has gotten into his fair share of questionable activity. And we need to show the Trump voters who chose him because they wanted change in who was running the country that did the exact opposite of that.
And how on earth is a billionaire executive who used to have a TV show and has never held elected office going to do that?
People, celebrities cannot govern. If the past year isn't evidence of this enough, then Democrats don't deserve to win in 2018 or 2020. Voters who are concerned about the economy in New Hampshire or Iowa or Alabama aren't going to vote for a rich actress from Hollywood.
The only thing separating Trump and Oprah (in my view) is that the president is a racist bigot hellbent on tearing this country apart, while Oprah has stood on the right side of issues. But we should be weary of getting used to the idea that celebrities make good political leaders. I mean, for one thing, if Oprah wanted to use last night as a way to launch a presidential campaign, she should have waited until the Golden Globes of 2019. People aren't going to be paying attention to these same issues when the presidential race begins. Already bad political maneuvering, and she hasn't even formed an exploratory committee yet.
I think Oprah's a good person who has worked to make change where she can throughout her life. But I will be very hesitant to cast a vote for her in 2 and half years.
Published by Ben Garfield
Author of The Garfield Political, in which I express my political musings and thoughts.	View all posts by Ben Garfield
Changing Liberalism
2020, Changing Liberalism, metoo, oprah
Just Because Someone's a Democrat Doesn't Make Them a "Better" Sexual Predator
Tom Cotton and His Staff are a Bunch of Lying Cowards
2 thoughts on "Oprah Running for President is a Bad Idea"
garfidh says:
Ben, read the New York Times from yesterday and Colorado politics, especially running for governor.
Ben Garfield says:
I have, but as someone who lives in Colorado and has been watching the governor's race, the article didn't tell me anything I didn't already know.


text:
Diarrhea & Dizziness With Magnesium Overdose
Uses of Magnesium Carbonate
Can Excess Calcium Cause Dizziness?
Side Effects of Magnesium on Kidneys
Chromium Nicotinate Side Effects
Side Effects of Magnesium Pills
Written by Rae Uddin
Magnesium pills are a type of nutritional supplement used to increase magnesium levels in people who do not have enough of this substance in their bodies. Foods rich in magnesium include nuts, whole grains, tofu and green leafy vegetables. While most people do not get as much magnesium as they should from their diets, a magnesium deficiency is rare, according to the University of Maryland Medical Center website. However, those with medical conditions such as irritable bowel syndrome and ulcerative colitis, diabetes, pancreatitis and hyperthyroidism can develop a deficiency. An intestinal virus can cause a temporary deficiency. Symptoms of a magnesium deficiency include anxiety, sleep disorders, irritability, restless leg syndrome, nausea, vomiting, abnormal heart rhythms and low blood pressure. Check with your healthcare provider before taking magnesium supplements.
While taking magnesium pills, you may develop diarrhea, the Office of Dietary Supplements reports. Frequent bowel movement urges may be uncomfortable and may occur in conjunction with nausea, vomiting or abdominal gas, pain or cramping. If you notice blood in your stools, which may cause your stools to appear unusually black or tar-like, seek prompt medical care. Bloody stools may indicate a severe reaction to magnesium pills.
While taking magnesium pills, you may develop diarrhea, the Office of Dietary Supplements reports.
Bloody stools may indicate a severe reaction to magnesium pills.
Abnormal Reflexes
Treatment with this nutritional supplement may cause you to develop abnormally slow reflexes, Drugs.com warns. Loss of normal reflexes may also be accompanied by muscle weakness or difficulty moving about normally. Such side effects are serious and require prompt attention from a medical provider.
Ingesting unusually high doses of magnesium may cause you to develop symptoms of overdose. Overdose complications are more common in people who have poor kidney function due to kidney damage or disease. Magnesium overdose symptoms include severe drowsiness, difficulty breathing, diminished heart rate, stomach upset, weakness, dizziness, loss of consciousness, blurred vision or coma. If you suspect that you or a loved one has overdosed on magnesium pills, seek immediate emergency medical care.
Ingesting unusually high doses of magnesium may cause you to develop symptoms of overdose.
Side Effects of Magnesium Taurate
Magnesium Deficiency Symptoms in Women
How to Take Potassium Pills
What Is the Difference Between Magnesium Glycinate and Magnesium Gluconate?
Effects of Zinc With Potassium
Drugs.com: Magnesium Side Effects - Magnesium
University of Maryland Medical Center: Magnesium
Rodríguez-Morán M, Guerrero-Romero F. Oral Magnesium Supplementation Improves Insulin Sensitivity and Metabolic Control in Type 2 Diabetic Subjects: A randomized double-blind controlled trial. Diabetes Care.2003 Apr;26(4):1147-52. doi:10.2337/diacare.26.4.1147
Office of Dietary Supplements/National Institutes of Health. Magnesium: Fact Sheet for Health Professionals. Bethesda, Maryland; updated July 11, 2019.
Kass LS, Poeira F. The effect of acute vs chronic magnesium supplementation on exercise and recovery on resistance exercise, blood pressure and total peripheral resistance on normotensive adults. J Int Soc Sports Nut. 2015;12:19. doi:10.1186/s12970-015-0081-z
Morais JBS, Severo JS, de Alencar GRR, et al. Effect of magnesium supplementation on insulin resistance in humans: A systematic review. Nutrition. 2017 Jun;38:54-60. doi:10.1016/j.nut.2017.01.009
Rosanoff A, Weaver CM, Rude RK. Suboptimal magnesium status in the United States: are the health consequences underestimated? Nutr Rev. 2012 Mar;70(3):153-64. doi:10.1111/j.1753-4887.2011.00465.x
Zhang X, Li Y, Del Gobbo LC, et al. Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials. Hypertension. 2016;68:324-33. doi:10.1161/HYPERTENSIONAHA.116.07664
Rae Uddin has worked as a freelance writer and editor since 2004. She specializes in scientific journalism and medical and technical writing. Her work has appeared in various online publications. Uddin earned her Master of Science in integrated biomedical sciences with an emphasis in molecular and cellular biochemistry from the University of Kentucky College of Medicine.


text:
Q: Simulating CTRL+C with Sendkeys fails I have an odd problem with Sendkeys, what my application basically should do is that, when I press ALT+ J, it'll simulate a CTRL+C operation (on any windows) to copy some highlighted text, however the CTRL+C simulation is not working.
[DllImport("user32.dll", SetLastError = true)]
[return: MarshalAs(UnmanagedType.Bool)]
static extern bool RegisterHotKey(IntPtr hWnd, int id, uint fsModifiers, uint vk);

private void Form1_Load(object sender, EventArgs e)
{
 RegisterHotKey(this.Handle,
 this.GetType().GetHashCode(), 1, (int)'J'); // Here it's waiting for the ALT+J
}

protected override void WndProc(ref Message m) // Function to c
{
 if (m.Msg == 0x0312) // If ALT+J pressed
 {
     Copier(); // .. Simulate CTRL+C (but doesn't work)
 }
 base.WndProc(ref m);
}

public void Copier() // Function to simulate the CTRL+C
{
 Debug.WriteLine("Ok ");
 InputSimulator.SimulateModifiedKeyStroke(VirtualKeyCode.CONTROL, VirtualKeyCode.VK_C); // First way
 SendKeys.Send("^(c)"); // Second way
}

A: I think this is happening because when you send CTRL+C you already have pressed the ALT modifier of ALT+J.
If you put
Thread.Sleep(1000);

just before send keys, you'll have time to release ALT+J and then CTRL+C will work.
Also, if you plan to check when your hotkey is released, check this.

redpajama_set_name: RedPajamaStackExchange


text:
School's In, Get Out and Play!
With the school year now in full swing, don't forget to let your kids play. Yes, play.
Research shows the more active kids are, the better they do in school. Not only does being active help kids burn off pent-up energy and focus better, it can also increase blood flow to the brain, which helps with memory and concentration—and let's not forget that exercise and playtime is great for their mood and self-esteem.
"No problem, my kid's on the soccer team," you say? That's great—just leave time for unstructured free play, too. Studies also show that, interestingly, children can get more exercise and enjoyment when engaged in non-competitive physical activities due to not being on the sidelines and other factors.
So help your kids balance "Study Hard" with "Play Hard." Here are quick tips to keep fun in the equation during the school year:
Long and short, it's all good: Short bursts of active play, even 15 minutes, all count toward the one hour or more of physical activity daily that health experts recommend.
Encourage "pretend" time: Let kids be creative to help develop their imagination and, when with other kids, their social skills.
Follow their lead: Being physically active together with your kids will boost their self-confidence and pride by letting them "be the boss" and help plan the fun you enjoy together.
If you live in the Washington, D.C., metropolitan area, one way for your kids to enjoy play time is to sign up your family and come out to play with KaBOOM! on October 5 at the inaugural Race for Every Child fundraiser to benefit Children's National Medical Center. Children's National, ranked consistently as one of the nation's top pediatric hospitals, serves more than 270,000 children a year from the region and across the country (and around the world), regardless of their families' ability to pay.
The race will feature a 5k run/walk and a Kids' Dash that start at Freedom Plaza, which also will be a giant play area that includes a KaBOOM! playground, great activities with FitKids, Superheroes of Southern Maryland and much more. Note you must register by October 3 at RaceForEveryChild.org, there will not be arrangements for walk-up participation. ABC Family's "Pretty Little Liars" star Ian Harding, a Maryland native, is heading up a fundraising team that you can support as well, and will be at the event awards ceremony. The top D.C.-area-based fundraiser on his team will get to meet him in person there.
If you don't live in the DC-MD-VA area, but want to support the cause, you can race "virtually" and donate at the same website, RaceForEveryChild.org.
Help Children's Claritin and KaBOOM! bring play to a school in need
Kids should have time to play - at home and at school. We know that creative play can make kids happier and healthier, but some kids are not getting enough of it. That's why we're teaming up with Children's Claritin® to make our schools more playful!
Children's Claritin® and KaBOOM! have launched a national program to bring Imagination Playground™ to four schools in need. Imagination Playground™ is an amazing mobile block-based play system that engages children's minds, bodies, and spirits through active, creative play. By interconnecting the components, children are able to build and rebuild their play spaces with each visit. Imagination Playground™ engages kids in creative play that is physically challenging and collaborative.
Twelve schools in Arizona, California, DC, Illinois, Louisiana, Missouri, New York, Ohio, Pennsylvania, South Carolina, Texas, and Washington are in the running—you can help us determine which four schools will receive an Imagination Playground™! Just visit Children's Claritin®'s Facebook page and vote once per day for the school of your choice. Voting runs through October 31, 2013.
See Imagination Playground™ in action and vote now!
Why play is critical to academic success -- tune into PBS on Sept 28
This Saturday, Sept. 28, be sure to tune into PBS to catch American Graduate Day 2013, a seven-hour live broadcast and outreach event. This "call-to-action" telethon will profile more than 20 national Community Partners, including KaBOOM!. Celebrity hosts such as Juju Chang, Brian Williams, Susie Gharib, Rebecca Jarvis and other journalistic luminaries will serve as anchors throughout the broadcast.
"American Graduate: Let's Make It Happen" is a national public media initiative that leverages the power and reach of public television to help communities across America address the high school dropout crisis. KaBOOM! is excited to see that play is being recognized as a critical component of a student's academic achievement and long-term success.
Our participants will be Dr. C.J. Huff, Superintendent of Joplin Schools, and CJ August, Special Education Instructor for the Beacon School. Joplin, Mo. was devastated by a tornado in May of 2011, which destroyed several schools in the area. Dr. Huff led the school district, and the community at large, in rebuilding efforts, pinpointing play opportunities for children as a critically important issue in the aftermath of the tornado.
In August of 2012, KaBOOM! partnered with Joplin Public Schools and the Kansas City Chiefs to build a playground at its Beacon School, which serves special needs children and didn't previously have a playground. Dr. Huff and Mr. August will be appearing on the show to speak about how the community came together to build the playground in one day (pictured above), and the difference the playground has made for the children at Beacon School -- academically, socially, and emotionally.
Don't miss this informative and inspiring national event! Check your local public television listings or watch the livestream starting at noon EST at americangraduate.org.
Investing in children through play
The 2013 Playful City USA Leaders' Summit: Investing in Children Through Play, sponsored by the Humana Foundation, is coming up on Sept. 23!
This invitation-only summit will bring together city, non-profit, foundation, business and national thought leaders from across the country to advance our collective efforts to ensure that all children get the play that they need to become healthy and successful adults. As the national platform for making play a priority in our communities, summit attendees will be inspired and challenged by preeminent leaders and will build strong networks with peers from across the country that enable cities to be transformed through play.
The summit will feature 11 Team Cities from across the country. The representatives from the Team Cities are doing some of the most innovative work to advance the cause of play in their communities. These communities take unique approaches to engaging partners to implement play agendas that give kids the childhood they deserve. Click here to learn more about our Team Cities.
Speakers include The Honorable Arne Duncan; The Honorable Kathleen Sebelius; Wes Moore, Host of Beyond Belief; and many more. Click here for a complete list of speakers.
Track and join the conversation at #playsummit.
How the Playground King transformed a county's schoolyards
Fifteen years ago, California resident Jim Roberts had no idea that he would be crowned Napa Valley's 'Playground King.' "I had an office supply store for 35 years," he says. "What do I know about playgrounds?"
Jim had retired from his business and was volunteering as an academic mentor at a school in a low-income neighborhood. One day, he stopped by the principal's office and found her terribly upset. A student had just fallen off a piece of equipment on the school playground and suffered a concussion.
"We went out to look at the playground," Jim says, "and I saw a cement curb only two feet away from the equipment. I could tell this wasn't safe. I said, this has got to be replaced, this is terrible."
The principal happened to have a catalog from the playground equipment company Landscape Structures in her filing cabinet. They began poring over the catalog and Jim soon enlisted the help of Landscape Structures to come up with a plan. When Jim took the plan to the school's Board of Directors, they proposed that he and his local Kiwanis club build the playground.
Jim says, "We dug in, and we got that playground down. It was sprinkling the whole time, but we didn't care. A part was missing and we had to race out and get it, but we got the playground together and saved the school a lot of money."
Jim was in his early 70s then. Now, at age 86, he has 58 playground builds under his belt, with three more in the works. "The Kiwanis club here is just incredible," Jim says, "they just roll up their sleeves and chip in. On five different occasions, we've built two playgrounds in the same weekend. We've even had members join the club just because they wanted to help build playgrounds."
Most of these playground builds have taken place at Napa Valley schools. Jim believes that playgrounds are a vital asset to a school community. "The kids just can't sit there and study all the time, they wouldn't hear anything after a while, they'd just turn off," he says. "It's important for them to get out and get fresh air, and have a challenging, fun, colorful playground. When they get out of class, they RACE, they RACE to that playground."
It's important for Jim that the playgrounds offer elements of challenge so children can learn and push themselves both inside and outside the classroom. Thinking back to his own childhood, Jim says, "I learned nothing on the playground. When I went to school, all we had was a turning bar. I remember digging holes in the ground and playing marbles. I want to provide for these kids what I didn't have."
He continues to be amazed by the challenges that children will rise to when given the opportunity. "Like overhead bars, for instance," he says. "My daughter was a principal, and she said, I want this for the kindergarten, and it was an overhead structure. I thought the kids were too small, but we put in the structure, and now these tiny little kids are going hand over hand, whipping across the thing!"
Of course, children need a safe place to play both inside and outside of school. Luckily, the schools in Napa Valley keep their playgrounds open to the surrounding community outside of school hours. "When the school builds a playground, that's recreation for the whole neighborhood," Jim says. "I pass by some of the playgrounds on a Saturday, and all kinds of kids are there with their parents doing this or that."
A recipient of multiple Let's Play Completion Grants from KaBOOM!, Jim acknowledges that the hardest part of building a playground is coming up with the funds. Beyond that, all it takes is a can-do spirit and a hardworking group of volunteers. The community build model that Jim has helped to popularize across the Napa Valley has not only saved the county over a million dollars—which they have used to invest in other park projects—but has helped the community feel more invested in the end product.
As Jim can attest, the "end product" is not just a collection of colorful equipment. "It's a hub for the whole neighborhood," he says. "A magnet for kids, doing something safe, good, and healthy; learning and challenging themselves; and most importantly, having fun."
Host a birthday party in the name of play
Somewhere along the way, Mom Sarah Hirsch realized that kids' birthday parties had become less about kids playing musical chairs and more about getting lots of elaborate presents.
When her son Harry turned one, he ended up opening one present every day, just so it wouldn't overwhelm him. "We were amazed that he got so much stuff," Sarah says. "It was so generous of our friends and family but also a little embarrassing to receive so many gifts for a one-year-old who was too little to care about presents."
During the following year, Sarah realized just how much her son was learning by playing at the area playgrounds. He was growing stronger, his language improved, and he was more aware of the world around him. When it came time to plan his second birthday, she had a new idea.
"I wanted to share our good fortune with others and thought, 'Instead of having people bring a present, why not ask them to give a donation?'"
She chose KaBOOM! because, as she says, "Everything Harry learns comes from play. What better organization to ask people to donate to than one that revolves all around the importance of play and bringing play to kids? I thought it was a perfect fit for us."
Sure, Harry still received presents, but Sarah gave guests an option to make a charitable contribution, which resulted in more than $500 donated in Harry's name.
As the year continued and Harry was invited to other kids' parties, Sarah continued the charitable trend. Her favorite gift is a $15 contribution to KaBOOM! and a copy of the KaBOOM! outdoor game guide, Go Out and Play!. "People are really flattered that we made a donation in their child's name," Sarah says.
Harry recently turned three, and Sarah knew how she was going to make his Sesame Street party even more special. "It was a no-brainer that we would do a KaBOOM! party again. Last year was really just the beginning of something that has become a cause in our family. We're passionate about the importance of play and KaBOOM! is near and dear to our hearts."
Donations for Harry's birthday totaled more than $600 this year. Sarah has gotten nothing but compliments from other parents for how she's "cutting down on the excess" that comes with birthday parties. "I think as Harry begins to understand more about the world, he'll be really proud of this, too."
When Good Is Not Good Enough
By Bill Shore, Darell Hammond and Amy Celep
Stanford Social Innovation Review
By some measures Share Our Strength and KaBOOM! were successful US nonprofits—growing rapidly, engaging numerous partners, and improving the lives of tens of millions of children. Yet all the while, the problems we were tackling—hunger and the lack of opportunities to play—were getting worse and even accelerating in recent years as the economy took a downturn. More than 16 million children in America now live in poverty, up from 11.6 million in 2000. We have witnessed how children who play on KaBOOM! playgrounds benefit physically, cognitively, socially, and emotionally, but we face the fact that one in three children is obese or overweight, and one in five suffers from a mental illness, with rates of depression higher than ever before. And the list goes on.
KaBOOM! and Share Our Strength realized that to make significant progress we had to move beyond simple solutions to complex problems, and we had to answer anew, in a much bolder way, the most critical question of all: "What does success look like?" Though it may seem counterintuitive for a non-profit sector already struggling to support, sustain, and scale up its impact—our approach calls for nonprofits to embrace a much heavier lift. We must look beyond short-term achievements that please funders, staff, and stakeholders but yield only incremental change, and instead hold ourselves accountable for the harder-to-achieve long-term outcomes that will ultimately solve social problems.
That is why KaBOOM! is committed to ensuring all children get the balance of active play they need to become healthy and successful adults. Together, we can give all kids the childhood they deserve.
>> Read the full article
Young changemakers will work for play
Children intuitively understand the importance of engaging in active play, every single day. While they may not be able to rationalize the cognitive, physical, and emotional benefits of play, they know that play makes them feel happier, helps them let off steam, and gives them a chance to be with friends.
Throughout the history of the play movement, some children have worked extra hard in the name of the play. The stories of these young play heroes will make you smile, if not jump for joy:
In 1995, a seven-year-old girl named Ashley Brodie was instrumental in planning and fundraising for the first KaBOOM! community playground build. A resident of Livingston Manor, the housing complex in Southeast DC where the playground would be built, Ashley had been looking at the empty lot outside her window for months and sketching designs for the playground she hoped to build there. When she met KaBOOM! founder and CEO Darell Hammond and learned about plans to transform the lot into a place to play, she immediately jumped in to help, slipping fliers under neighbors' doors and walking around to neighborhood restaurants to put donation canisters on the counters. She also personally collected $9.97 in pennies. As the build date commenced, she asked permission to stay home from school so she could help the volunteers and watch her longtime dream come to life.
> Read our new children's book inspired by Ashley's story, My Dream Playground.
When Alex Griffith of Forest Hill, Md. learned that the playground at the hospital where he was born was in severe disrepair, he took it upon himself to build a new one. Adopted from Krasnoyarsk, Russia, Alex said, "Russia is part of me and this hospital is part of me. They gave me life, so I [wanted] to give back to them, to give them a fun place to play." Alex spent six months researching the existing playground, then proposed the idea for his Eagle Scout Project. To get support, he sold candy, put on a car show, launched a letter writing campaign, went to local business meetings, and forged relationships with Rotary International and various adoption groups. Alex designed the playground himself, incorporating the red white, and blue colors of both the Russian and American flags. Finally in August 2009, more than two years after committing to the project, Alex traveled to Krasnoyarsk to help bring the design to life, and to celebrate his 16th birthday with the grand opening of his playground.
Last summer, a year before Detroit formally declared bankruptcy, a nine-year-old boy named Joshua Smith decided he wanted to help his struggling hometown. He sold lemonade and popcorn in front of his house in the hopes of raising at least $1,000 to improve the city's parks. Not only did he end up far exceeding his fundraising goal, but his story caught the attention of Kevin Cook, an executive from playground manufacturing company Playworld Systems. The company surprised Joshua on his birthday with plans to build a $50,000 play structure at a nearby park. When Joshua heard the news, he said, "I feel really great!" And so he should!
In spring of 2012, when a city council in Canterbury, UK announced plans to build housing on Kingsmead field, neighborhood kids painted enormous signs to protect their beloved playspace. Orla and Timmy, ages 10 and 11 respectively, attended a city council meeting to take a stand. Orla said: "It's not just for me and my friends but for all the people of the area who live and breathe better because there is a lovely empty green field nearby." Said Timmy: "Often in the evenings, I go to the field and play football with my dad and brother. It's very easy to stay indoors and watch TV or play computer games. Please leave our field alone." Over a year later, they are still fighting the good fight.
In 2010, students at Mount Washington Elementary in Louisville, Ky. prepared a report for a class project to convince school administrators to lengthen recess time. They researched the importance of physical activity and compared their recess time—10 minutes—to that of other schools in the district. When the students presented their findings, the school council discovered that it wasn't enforcing its own wellness policy, and extended recess to meet the recommended minimum of 15 minutes. Perhaps a future class can lobby to exceed to minimum!
Do you know any extraordinary children who have gone the extra mile to spread the joy of play?
My Dream Playground — the story of a girl whose dream came true
"I dream about having a playground — a real playground, a fun playground — in our neighborhood. But all we have is an empty lot down the street from my apartment."
When a little girl sees a man measuring the empty lot, she's sure that he's there to help make her playground dream come true. And he is!
Inspired by the real story of the first-ever playground build by KaBOOM!, here is the story of how a determined young girl, with the help of her family, friends and community, makes her dream playground in her own neighborhood a reality.
"This book may inspire more than dreams," notes Kirkus Reviews. Written by Kate Becker, VP of Program Management at KaBOOM!, the book's spirited prose is brought to life by illustrator Jed Henry's "charmingly childlike" pictures (Kirkus Reviews).
Sadly, like the girl depicted in this book, all too many children lack access to a safe place to play. They will learn that with spirit and resolve, they too can make their playground dreams come true.
Get your copy today at Amazon or from your local bookstore.
How a dog is changing lives on the playground
No dogs allowed? No kids allowed? When it comes to play spaces, dog owners and parents sometimes find themselves at odds. Not so at Jefferson Elementary School in Playful City USA community Missoula, Montana, where a new "barrier-free" playground includes a space for the city's many dogs (and their owners) to play.
But Scout doesn't just play at Jefferson; he has a job to do. A four year-old English Lab, Scout serves as an assistant to Nancy Jo Connell, a speech-language pathologist with the Missoula County Public Schools district. Nancy Jo enlists Scout's help to work with students to overcome communicative difficulties, autism, and emotional or physical problems, in a process known as animal-assisted therapy.
Before the new barrier-free playground was constructed, Nancy Jo and Scout had been working with students inside the classroom. Nancy Jo has since found that the new outdoor play space is expanding Scout's therapeutic potential.
Being out on the playground, she says, allows the kids to release steam and reduce stress. It also adds a social dimension to the therapy sessions, since the children participating in therapy can invite their peers on the playground to come play with Scout.
A favorite outdoor activity is grooming Scout, which helps to increase children's coordination and fine motor skills. For some, especially those on the autism spectrum, the pet grooming process can be calming. Other favorite play activities with Scout, including hide-and-seek and fetch, increase physical activity and motivate students to learn language commands like "fast, slow, and stop."
In fact, one boy with autism uttered his very first words at school while playing fetch with Scout. The boy tossed the ball multiple times, watching Scout retrieve it, but after one toss, Nancy Jo gave Scout the signal to stay. Expecting the dog to get the ball, the boy finally shouted, "Go!" When he went home that night, he pointed to a copy of Clifford the Big Red Dog, and turning to his mother, said, "Puppy."
As Scout demonstrates, dogs and kids can not only play "nice," but dogs with the right training and disposition can actually help children with special needs reduce stress, bridge social divides, and improve their fine motor and language skills. Something as simple as a game of fetch can lead to developmental breakthroughs.
Could dogs like Scout become a fixture at other school and public playgrounds? After all, innovation doesn't have to mean elaborate new-fangled play structures. It can simply mean opening the playground gates to something we already have.
Photo courtesy of Jefferson Early Learning Center.


text:
Something is really rotten in the state of Kentucky, and it's coming from Russia
Joan McCarter / Daily Kos (04/24/2019)
Gage Skidmore / Flickr
The opinion editors back home in Kentucky are not really thrilled with the idea of the Russians getting an economic hold on the state. Not just the Russians, but the Russian mob. At the Louisville Courier Journal, Joseph Gerth is not too excited at the prospect that "by the middle of the year, we'll be in business with Oleg Deripaska, a buddy of Vladimir Putin." Kentucky is looking for $200 million from the Russian to invest in a $1.7 billion aluminum plant there. He goes on to describe Deripaska's "deep ties to Russian organized crime," and the allegations of Deripaska's violent, ruthless, criminal past in Russia.
Gerth's angle is Republican Gov. Matt Bevin's support for this project—the state has already spent $15 million in the Braidy Industries aluminum plant, and how important getting this big project going for Bevin's re-election, as "there has been an air of suspicion surrounding the Braidy project as it has dragged on." It took the intervention of two other powerful Kentucky politicians to make it happen—Sens. Rand Paul and, most importantly, Mitch McConnell. Those two were among the three votes in the Senate that helped Donald Trump lift sanctions against Rusal, the aluminum company that will invest in the state which is partially owned by Deripaska. Or, as far as we know, "officially" partially owned. Things are fluid in Russian corporate structure.
And you all remember Deripaska—he's good buddies and a former employer of Donald Trump's first campaign manager, Paul Manafort. The Trump/Manafort/Russia and specifically Deripaska (friend of Putin!) connection is deep and complicated and at the heart of the NO COLLUSION collusion that helped land Trump in the White House.
Once again, all of this brings up one key question: how deep into Russia is McConnell? What does he owe Putin? He helped Russia get Trump into the White House by refusing to let the American government notify the public about and help states arm against Russian incursion in the 2016 election. Now he's looking to Russia to help his own re-election prospects and stranglehold on the Senate, with a big assist from Bevin and Paul.
Something is really rotten in the state of Kentucky.
VIAJoan McCarter
MitchMcConnell
OlegDeripaska
RandPaul
2 Comments on "Something is really rotten in the state of Kentucky, and it's coming from Russia"
DHG
It appears Kentucky has seceded
McConnel has been laundering money fro Russia for a long time. He is a slime bag just like Trump. They are both swamp creatures. Kentucky better wake up and vote them out of office next year.


Is it necessary for a municipality to explicitly state its legislative intent when amending its zoning code?
A municipality has indicated that it wants to encourage adaptive reuse of institutional buildings, in particular a defunct church for which condo land development is proposed.
The municipality has drafted an amendment to its ordinance on nonconforming uses which would allow such a conversion by conditional use, but nowhere does it state the legislative intent. Are there any potential pitfalls to not being explicit about the objective?
Strictly speaking, it isn't "necessary" for a municipal governing body, such as a city or town council, to state their legislative intent when they change the zoning ordinance.
Making the legislative intent clear, though, probably would help, perhaps a lot, in the event of a lawsuit challenging the municipal action.
Legislative intent is a term that may be unfamiliar to some readers, but think of your city council as "legislators." So legislative intent is simply the rationale--stated and sometimes not stated explicitly--for certain changes.
Notice that we said that legislative intent maybe does not have to be shown through a nice, neat, eloquent statement included in the resolution or ordinance or law enacting the zoning change.
Legislative intent might be supported in court by oral statements that council people make in response to the public hearing. Conceivably it could be shown by asking that certain items be entered into the public record.
For the best possible showing of legislative intent, however, it is still a good idea to write good succinct statements of that intent into the resolution by which the zoning law is changed.
The pitfall of not being explicit is that you may be misunderstood. Particularly at the level of lower courts, the knowledge of zoning and zoning theory may not be all that sophisticated. It's certainly certainly less expensive to do the job right the first time.
Regarding your final paragraph, your terminology may be very accurate for your local situation, but it wouldn't be typical. So please forgive us if we just leave the specifics of that alone.
This leads us to comment on one other point that would be important for all of our other readers. While it's definitely good to show legislative intent if what a governing body is doing would be considered outside the mainstream of good practice in enacting zoning regulations, there could be a different problem: your city could be enacting something like special legislation to support this particular zoning ordinance change.
An overriding principle of good zoning practice is that equal properties should be treated equally under the law. If the facts of the zoning case begin to be so specific that you are setting up something that logically would apply only to this one instance, in all probability, you should be concerned about this.
So the bottom line is to have a detailed conversation about this situation with your municipal attorney.
If you are in or near a metropolitan area where there may be several attorneys or law firms that specialize in municipal law, it can't hurt to obtain more than one opinion about the particular facts of your case as well.


text:
Development of Improved Sandwich Elisa for the In Vitro Detection of Inhibitors of the TNF-TNFR1 Interaction | OMICS International
Development of Improved Sandwich Elisa for the In Vitro Detection of Inhibitors of the TNF-TNFR1 Interaction
Jessica M Davis*
Department of Chemistry & Biochemistry, Fairfield University, BNW 315, USA
Jessica M Davis, Ph.D
Fairfield University, BNW 315, USA
Tel: 203-254- 4000 x2123
Received date: November 04, 2011; Accepted date: December 22, 2011; Published date: December 24, 2011
Citation: Davis JM (2012) Development of Improved Sandwich Elisa for the In Vitro Detection of Inhibitors of the TNF-TNFR1 Interaction. J Anal Bioanal Tech 3:129. doi: 10.4172/2155-9872.1000129
Copyright: © 2012 Davis JM. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The over-expression of tumor necrosis factor alpha (TNF-alpha) has been associated with various diseases, particularly autoimmune diseases such as rheumatoid arthritis and Crohn's disease. Some biologic therapies for these diseases specifically target this cytokine, sequestering it, and preventing its interaction with its 55 kD receptor (TNFR 1 ). While these therapies have proven the validity of this approach, they are large proteins that require intravenous administration. Small molecule inhibitors of this interaction are highly desirable and some have been developed. However, such inhibitors have not been reported to have successfully completed clinical trials. One prohibition to this approach is the current state of in vitro testing of such molecules. Assays have been developed that use radio labeled or biotin labeled TNF-alpha. In vivo methods exist, but are cost prohibitive to screening a large selection of molecules. Reported here-in is an inexpensive, highly robust, sensitive assay for inhibitors of the TNF- alpha interaction with TNFR 1 that does not require modification of TNF-alpha. The simplicity of this assay should allow for increased investigation into inhibiting this important interaction.
TNF: Tumor Necrosis Factor Alpha; TNFR1: Tumor Necrosis Factor 55 kD Receptor; ELISA: Enzyme-Linked Immunosorbant Assay; sTNFR1: Soluble TNFR1; PBS: Phosphate Buffered Saline; BSA: Serum Bovine Albumin; HRP: Horseradish Peroxidase
The overexpression of the cytokine tumor necrosis factor alpha (TNFα) has been linked to inflammation in Crohn's disease and rheumatoid arthritis and has proven to be a viable therapeutic target in the treatment of these diseases [1,2]. Current therapies that target TNFα are the biologics infliximab, etanercept, and adalimumab. These are antibodies or small proteins that work by sequestering TNFα or by blocking the interaction with its 55 kD receptor (TNFR1). Due to the size of these molecules, they require intravenous administration and have poor efficacy [3]. As exemplified in a Current News article in Nature Biotechnology, therapeutics that are orally bioavailable, drug-like molecules with increased specificity and potency over the current treatments are highly desirable [4].
Small molecules that are proposed to function by binding TNFα, such as suramin [5,6] and the saponins [7], have been identified as inhibitors of TNFα function (Figure 1a and d, respectively). Other research groups have developed small peptide antagonists of TNFα, including a library of D-amino acid hexapeptides [8], a derivative of TNFR1 [9], and the peptide WP9QY (Figure 1b) [10]. Targeting this interaction with small molecules that bind TNFR1 has been successful with IW927 (Figure 1c) [11].
Figure 1: Four known inhibitors of the interaction between TNFα and TNFR1. Interaction with the proteins were tested through biotin or radio-labeled TNFα a) Suramin, a natural product from, IC50 = 35 μM (125I or Eu- or biotin-labeled TNFα used in assay) [5,6]; b) WP9QY, peptidomimetic developed by Takasaki et al. [10], IC50 = 5 μM (125I-labeled TNFα used in assay) [10]; c) IW927, small molecule developed by Carter et al. [11], IC50 = 50 nM (Eu-TNFα based assay) [11]; and d) Saponin, a natural product [7].
Considering the validation of this target through current therapeutics, it is disappointing to see a lack of small molecule inhibitors that would be orally available compared to the intravenous treatments currently used. While targeting a large protein-protein interaction with small molecule inhibitors poses significant challenges, it has been successfully achieved for the TNFα interaction with TNFR1 [5-7,11,12]. One prohibitive factor in finding inhibitors of the TNFα interaction with TNFR1 is the lack of easily accessible in vitro assay conditions for preliminary screening. The most common type of assay uses radiolabeled TNFα [10,11,6,8] or radio-labeled inhibitors [13]. The special facilities and training needed to utilize these assay conditions imposes a safety and financial constraint. Biotin-labeled TNFα is also used [6,14]; although this technique does not require the facilities and training of radiolabeling, biotin labeling of TNFα is expensive and results in low yields. A kit targeting this interaction from PerkinElmer™ became available in 2003, but requires the use of a special plate reader with AlphaScreenTM technology [15].
Compared to currently available techniques, the assay described here provides a more accessible format, is time and cost effective, and utilizes commercially available reagents. The technique is a sandwich enzyme-linked immunosorbant assay (ELISA) which is modified from the techniques used by Corti et al. [16] for elucidation of the binding of TNFα with TNFR1 and the TNFα quantification by Alzani et al. and Mancini et al. [6,14]. The method used by Corti et al. [16] uses sandwich ELISA formats, where plates are coated with anti- TNFα which are then treated with TNFα containing solutions (either with or without TNFR1). Ideally only free TNFα binds to the antibody; however, it was found that both free and TNFR1 bound TNFα are detected. The scope of effectiveness depended upon varying assay conditions. Based upon this result, it would be ideal to eliminate the ambiguity between bound and unbound TNFα by eliminating the primary antibody step. The technique used by Alzani et al. and Mancini et al. [6,14] utilizes a similar sandwich ELISA technique; however, the plates are coated with sTNFR1 initially and then treated with biotin-labeled TNFα. This process directly measures the binding of TNFα to sTNFR1. Nevertheless, the required biotin-labeled TNFα imposes a time, cost, and yield constraint on the availability of this assay protocol. The technique de-scribed here-in uses sTNFR1 coated plates, unaltered TNFα, and detects TNFα binding using a commercially available biotin labeled antibody with a streptavidin-enzyme. This technique eliminates any ambiguity by directly measuring TNFα binding and does not require the use of biotin- or radio-labeled- TNFα.
Tumor necrosis factor soluble receptor 1 (TNF sR1)/Fc Chimera Human, Recombinant, expressed in mouse NSO cells (sTNFR1), sura min, phosphate buffered saline (PBS), bovine serum albumin (BSA), carbonate-bicarbonate buffer, Greiner® high-binding well plates, and TWEEN-20 was purchased from Sigma-Aldrich, Inc. Recombinant human TNFα (expressed in Escherichia coli), biotinylated anti-human TNF-a/TNFSF1A antibody, streptavidin-horseradish peroxidase (HRP), HRP substrate solution (3,3', 5,5'-tetramethylbenzidine (TMB)), and HRP stop solution (0.16 M sulfuric acid) were purchased from Thermo Scientific. The peptide WP9QY (sequence YCWSQYLCY with disulfide bond constraint) was purchased through PierceNet. The plate reader used is a Biotek® Epoch microplate reader and all data was processed with SigmaPlot® [17].
sTNFR1/TNFα sandwich ELISA protocol
Using a 384 well high-binding plate, 50 μL of a 25 ng/well sTNFR1 solution in 0.05 M carbonate-bicarbonate buffer (pH 9.6, 25°C) was incubated overnight (16 hours) at room temperature. The plate was aspirated and washed three times with wash solution (PBS/1% TWEEN-20, pH 7.3, 25°C) for 10 minutes each. Unbound sites were blocked using a 10% BSA in PBS (pH 7.3, 25°C) solution (140 μL/well) and incubated for 1 hour at 37°C. The plate was aspirated and washed three times with wash solution for 10 minutes. Plates can be stored up to two weeks with 140 μL/well PBS/4% BSA. Wells were treated with TNFα and with inhibitor as described in the procedures below. The plate was aspirated and washed three times with wash solution for 10 minutes each. 50 μL of 0.25 mM anti- TNFα (biotin) was added to each well and incubated at 25°C for 1 hour. The plate was aspirated and washed three times with wash solution for 10 minutes each. 50 μL of 2.5 μM streptavidin-HRP was added to each well and incubated for 30 minutes at room temperature. The plate was aspirated and washed three times with wash solution for 10 minutes each. 40 μL of HRP-substrate solution (TMB) was added in the dark and incubated for 30 minutes at room temperature, followed by 40 μL of HRP stop solution. After shaking for 20 minutes, the plate was read at 450 nm minus 550 nm (Table 1).
Step 1 Parameter Amount/Well (µL) Concentration Buffer* Incubation
1 Coat wells STNFR1 50 0.25 µg/mL A 16 hours 25°C
2 Wash TWEEN-20 140 1% B 10 minutes 3 times, 25°C
3 Block wells BSA 140 10% B 1 hour, 37°C
5a Saturation TNFα 50 Serial dilutions from 100nM C 2 hours, 25°C
5b Inhibition Serial dilutions from 100 nM C 2 hours, 25°C
TNFa 25 14 nM (7 nM final) D 2 hours
inhibitor 25 Serial Dilution D 25°C
7 Anti- TNFα(biotin) 50 0.25 mM C 1 hour, 25°C
9 TMB 40 30 minutes, 25°C
10 Sulfuric acid 40 0.16 M 20 minutes, 25°C
11 Read at 450 nm minus 550 nm
*Buffer A: 50 mM Carbonate-bicarbonate (pH 9.6), B: PBS, C: 4% (v/v) BSA in PBS (pH 7.3), D: 4% BSA (v/v) in PBS, 2.5% (v/v) DMSO (pH 7.3).
Table 1: Sandwich ELISA.
sTNFR1/TNFα sandwich ELISA concentration studies
The assay protocol described above was tested for minimal concentrations of all the proteins utilized. sTNFR1 concentration was tested with serial dilutions from 2.5 μg/mL sTNFR1 with 5.0 nM TNFα. Concentrations for anti- TNFα -biotin were tested from 1:10 dilutions starting from 50 μg/mL. Concentrations for streptavidin-HRP were tested from 1:10 dilutions starting from 1:750 dilution of stock solution. Minimum acceptable detection of Bmax was assessed through maximum absorbance values and calculation of the z-factor from Bmin.
sTNFR1/TNFα sandwich ELISA saturation studies
Using a 384 well high-binding plate bound with sTNFR1 and blocked with BSA as described previously, wells were treated with 50 μL pre-prepared serial dilutions of TNFα from a starting concentration of 100 nM in PBS/4% BSA (pH 7.3, 25°C) for 2 hours at room temperature. Incubations of TNFα with sTNFR1 were tested with cona centrations of DMSO from 1 – 10% (v/v), varying the pH of the buffer from 5 to 7 with 0.1 M HCl and 8 – 9 with 0.1 M NaOH, and incubation times from 1 – 8 hours. Detection of TNFα was carried out as described previously.
sTNF1/TNFα sandwich ELISA inhibition studies
Using a 384 well high-binding plate bound with sTNFR1 and blocked with BSA as described previously, the wells are treated with 25 μL of serial dilutions of inhibitor in (4% BSA, 5% DMSO in PBS) with 25 μL of 14 nM TNFα in PBS/4% BSA (resulting in 7 nM final concentration), preincubated for 15 minutes, and then for two hours at room temperature. Detection of TNFα is carried out as described previously.
Plate uniformity and z-factor study
Using two 384 well, wells in columns 3, 9. 12, 15, 18, 21, and 24 of three high binding plates were bound with sTNFR1 and blocked with BSA as described previously. Wells of the three plates were treated with 50 μL of either 25nM, 6.25 nM, or 0.01 nM TNFα PBS/4% BSA (pH 7.3, 25°C) and incubated for 2 hours at room temperature. Detection of TNFα was carried out as described previously.
Data was analyzed using SigmaPlot®. For KD or EC50 calculations, the macro for ligand binding single site saturation (y= (Bmaxx)/(KD+x)) or sigmoidal dose response (y= (max-min)/(1+10(logEC50-x)) curves were used, respectively. For IC50 calculations, the macro for ligand binding one site competition (y= (max-min)/(1+10(logEC50-x)) was used. The zfactor was calculated using 1-(3(σmax-σmin))/|averagemax-averagemin|.
The assay conditions described were optimized over a series of experiments to obtain the ideal concentrations for both saturation and inhibition curves. Both cost and detection levels were considered in deciding on the final conditions. In addition, various experimental conditions, including varying the percent DMSO and pH were tested to ensure consistency of the results.
Concentration experiments
Standard solutions were tested to make certain that the absorbance was detecting only the adhesion of TNFα to TNFR1. Of the twenty-two permutations tested, only those experiments containing all of the assay components gave significant absorbance values (0.39 ± 0.03, 3.5 nM TNFα, n=4). Using HRP, substrate, and stop solution alone gives a low absorbance value (0.047 ± 0.005, 3.5 nM TNFα, n=4) and is recommended for use as a blank.
Exploration of minimal concentrations of all the proteins and antibodies was performed and final concentrations were chosen based on effectiveness and cost. The concentrations of TNFR1, antibody, and HRP were tested keeping the concentrations of all other components constant, chosen from the concentrations originally used by Alanzi et al. [5,6] or recommended from the reagent suppliers. The most cost effective concentrations were tested using concentrations that gave an appreciable signal, which were 0.25 μM sTNFR1, 0.25 mM biotin-anti- TNFα, and 2.5 μM streptavidin-HRP (Figure 2a).
Figure 2: a) TNFα saturation curve with optimized assay parameters (0.25 μM sTNFR1, 0.25 mM biotin-anti- TNFα, and 2.5 μM streptavidin-HRP). Control is with no TNFR1; b) Suramin inhibition curve with 7 nM TNFα, IC50 = 0.39 mM, R2 = 0.90.
For inhibition curves (Figure 2b), a final concentration of 7 nM TNFα can be used with an acceptable change in absorbance (z-factor = 0.62, Figure 4). Any new reagent must be retested for optimal effective concentration.
Figure 3: a) Effect of increasing the %DMSO during incubation of TNFα with sTNFR1 on the KD (nM); b) Effect of increasing pH during TNFα incubation with sTNFR1 on the KD (nM); c) TNFα saturation curve with 1 - 8 hours incubation of TNFα with TNFR1, R2 > 0.98 for all curve fits.
Condition tests
Preference to maintain cell-like conditions make it preferable to maintain low DMSO levels. However, DMSO is often a necessary component to solubilize compounds for inhibitition studies. Tolerance for DMSO is tested in the saturation curve to find how its presence effects the KD. Varying the percent DMSO from 0 to 10% (v/v) during the incubation of TNFα with sTNFR1 showed little variation in the dissociation constant between 4 - 7% DMSO, as seen in Figure 3a. This result is valuable in finding hydrophobic compounds that can disrupt the protein-protein interaction since addition of DMSO is often necessary to dissolve such compounds in water at the concentrations needed for preliminary studies. The increase in the KD with increasing levels of DMSO may indicate increase solubilization of the trimeric structure of TNFα; however, further studies would have to be conducted to verify this hypothesis.
Variations in pH were also tested to ensure that addition of acidic or basic compounds beyond the buffer range will not greatly affect the dissociation constant. Figure 3b shows that the KD is stable between pH 6 to 9. Repeated experimentation confirms that the assay is less stable at lower pH.
Incubation of TNFα with sTNFR1 can be varied from one to eight hours without any significant effect on the KD, as seen in Figure 3c.
Storage tests
The total time required to complete the assay is 20 hours. To reduce the consecutive time commitment, plates coated with TNFR1 and BSA were stored for up to 4 weeks in PBS/4% BSA buffer at 4°C. Using plates thus stored allows for a number of plates to be prepared and saved, then continuing the assay from the point of addition of TNFα and inhibitor. This is ideal when screening a large number of compounds. After two weeks storage there is a 10 fold change in KD. Addition of a preservative, such as sodium azide, may increase the longevity of the plates, but this has not been tested.
Three known inhibitors were tested, suramin, saponin, and the constrained peptide WP9QY. These inhibitors were chosen because of their commercial availability. The inhibitors gave comparable results to the literature values, which further validates the assay design. Suramin, saponin, and the constrained peptide WP9QY, giving 63%, 41%, and 67% inhibition, respectively, with 1 mM inhibitor and 7.0 nM TNFα. Takasaki et al. [10] report 75% inhibition at 1 mM WP9QY. Suramin was further tested, giving an IC50 of 0.39 mM, which is comparable to the value reported by Alzani et al. [5] of 0.65 mM using radiolabeled- TNFα assay since both methods use a direct detection technique for TNFα binding. Investigation of inhibitors for the TNFα interaction with TNFR1 may require increased incubation time. Incubation of TNFα with sTNFR1 can be varied from one to eight hours without any significant effect on the KD, as seen in Figure 3c.
The difference in the proposed mechanism of these inhibitors, suramin disrupting the TNFα trimer and WP9QY mimicking a binding region of TNFR1, validates the versatility of the assay. Only the direct detection of TNFα bound to sTNFR1 is measured, allowing for a variety of antagonist mechanisms.
A cost effective, safe assay has been developed for testing inhibitors of the TNFα interaction with TNFR1. The assay is based on a sandwich ELISA format and has been optimized for low concentrations of most proteins. The total time required to complete an experiment is 20 hours; however, plates coated with TNFR1 and BSA can be stored for up to two weeks without diminishing the reliability of the results. The assay is also effective between 4-7% DMSO and between pH 6-9. Extending these assay conditions to the TNFα -TNFR1 interaction should be a relatively simple exchange of the protein in the first step and warrant further investigation. The hope is that this assay will provide researchers with more accessible conditions and at a lower cost than what is currently available for preliminary screening of inhibitors of this important protein-protein interaction.
This project was supported by a Research Corporation Cottrell College Research Award ID 7715, NIH-AREA 1R15DK081934-01A1, and start-up support from Fairfield University.
Dinarello CA (1991) Inflammatory Cytokines - Interleukin-1 and Tumor-Necrosis-Factor as Effector Molecules in Autoimmune-Diseases. Curr Opin Immun3: 941-948.
Kodama S, Davis M, Faustman DL (2005) The therapeutic potential of tumor necrosis factor for autoimmune disease: a mechanistically based hypothesis. Cell Mol Life Sci62: 1850-1862.
Atzeni F, Turiel M, Capsoni F, Doria A, Meroni P, et al. (2005) Autoimmunity and anti-TNF-alpha agents. Ann N Y Acad Sci 1051: 559-569.
Sheridan C (2008) Small molecule challenges dominance of TNFα inhibitors. Nat Biotechnol26: 143-144.
Alzani R, Corti A, Grazioli L, Cozzi E, Ghezzi P, et al. (1993) Suramin induces deoligomerization of human tumor necrosis factor α. J Biol Chem268:12526-12529.
Alzani R, Cozzi E, Corti A, Temponi M, Trizio D, et al. (1995) Mechanism of suramin-induced deoligomerization of tumor necrosis factor α. Biochemistry 34: 6344-6350.
Shah B A, Chib R, Gupta P, Sethi VK, Koul S, et al. (2009) Saponins as novel TNF- α inhibitors: Isolation of saponins and nor-pseudoguainanolide from Parthenium hysterophorus. Org Biomol Chem 7: 3230-3235.
Kruszynski M, Shealy D J, Leone AO, Heavner GA (1999) Identification of TNF- α binding peptides from a D-amino acid hexapeptide library that specifically inhibit TNF- α binding to recombinant p55 receptor. Cytokine11: 37-44.
Cao Y, Wang Z, Bu X, Tang S, Mei Z, et al. (2009) A Synthetic Peptide Derived from A1 Module in CRD4 of Human TNF Receptor-1 Inhibits Binding and Proinflammatory Effect of Human TNF-α. Inflammation32: 1573-2576.
Takasaki W, Kajino Y, Kajino K, Murali R, Greene MI (1997) Structure-based design and characterization of exocyclic peptidomimetics that inhibit TNFα binding to its receptor. Nat Biotechnol 15: 1266-1270.
Carter P H, Scherle PA, Muckelbauer JK, Voss ME, Liu RQ, et al. (2001) Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF- α. Proc Natl Acad Sci U S A 98: 11879-11884.
He MM, Smith AS, Oslob JD, Flanagan WM, Braisted AC, et al. (2005) Small-molecule inhibition of TNF-α. Science 310: 1022-1025.
Loetscher H, Gentz R, Zulauf M, Lustig A, Tabuchi H, et al. (1991) Recombinant 55-kDa Tumor Necrosis Factor (TNF) Receptor: Stoichiometry of binding to TNF α and TNF β and inhibition of TNF activity. J Biol Chem 266: 18324-18329.
Mancini F, Toro CM, Mabilia M, Giannangeli M, Pinza M, et al. (1999) Inhibition of tumor necrosis factor-alpha (TNF-alpha)/TNF-alpha receptor binding by structural analogues of suramin. Biochem Pharmacol58: 851-859.
Bouchard N, Legault M, Wenham D (2003) AlphaScreenTM TNF α binding assay kit: A homogenous, sensitive and high-throughput assay for screening TNFα receptors. PerkinElmer BioSignal.
Corti A, Poiesi C, Merli S, Cassani G (1994) Tumor necrosis factor (TNF) alpha quantification by ELISA and bioassay: effects of TNF alpha-soluble TNF receptor (p55) complex dissociation during assay incubations. J Immun Meth 177: 191-198.
SigmaPlot®, Copyright© 2010 Systat Software Inc. - All Rights Reserved.
March-2012 - Jan 21, 2021]
HTML page views : 9041


Pupils with special educational needs (SEN) in England are dropping further behind their classmates in national primary school tests, statistics show.
The gap between SEN pupils and their peers has risen from 48 percentage points in 2016 to 52 this year.
The figures are revealed in school league tables, published by the Department for Education (DfE), showing the results of about 16,000 primaries.
Head teachers say special-needs education funding is in crisis.
The government statistics show 18% of children with SEN reached the expected level in reading, writing and mathematics, compared with 70% of their peers without special needs.
Although SEN pupils' results edged upwards on last year, when 14% made the grade, their non-SEN peers boosted their results more dramatically from 62% to 70%.
Teachers have been warning that pupils with special needs, such as mild autism or dyslexia, would struggle in the tougher tests introduced last year.
A National Association of Head Teachers' spokesman said it was "one of those situations where money is the solution and schools need the government's help".
The tables also showed disadvantaged pupils still perform far worse than all other pupils in England, with around half passing the tests, compared to nearly two-thirds of non-disadvantaged.
The gap between the two groups of pupils is now as wide as it was in 2012 at about 20 percentage points.
However, there does appear to be a small catch-up (one percentage point) in poorer pupils' attainment on 2016 when the tougher tests were introduced and results for all pupils dipped significantly.
NAHT general secretary Paul Whiteman said: "This data is a useful indication of school performance but it is not the whole story. One thing it does do, though, is confirm what NAHT has been saying for a long time about social mobility.
"Raising the Key Stage 2 standard (Sats test) was not going to help close the gap. The issues that underpin inequality reach far beyond the school gates and exist throughout the communities that schools serve."
But Schools Minister Nick Gibb hailed the achievements of pupils and teachers, saying they had responded well to the more rigorous curriculum.
This set of pupils was the first to benefit from the government's new approach to phonics, he said.
"Pupils are now leaving primary school better prepared for the rigours of secondary school and for future success in their education," Mr Gibb added.
Overall, pupils have scored better in their Sats results than last year, which was the first year of the new tests.
The DfE said this was partly because of "increased familiarity" with the new tests.
There was a nine percentage point increase in the proportion of black pupils passing the tests, to 60% - just one percentage point behind the national average and white pupils.
The top five local authorities were all London boroughs, with Richmond upon Thames at the top, Kensington and Chelsea coming second and Bromley third.
The inner city boroughs of Hammersmith and Fulham and Hackney have claimed the fourth and fifth spots.
In 1999, Hackney, which had been one of the worst performing boroughs, became the first local education authority to be taken out of council control.
In this year's tests across England, local authority schools slightly outperformed academies and free schools, with 62% of their schools reaching the expected standard compared with 61% of academies and free schools.
In all, 511 schools - 4% of the total - have fallen beneath the government's expectations or "floor standard", where fewer than 65% of pupils met the expected standard in reading, writing and mathematics and the school did not achieve sufficient progress scores in all three subjects.
This is an improvement on last year, where 665 - 5% - primaries were found wanting.


We can learn a bit about the name of the town, the name of the river, and the word for the stones that mark the camino. They all derive from hito (Fitero, Itero, and hito), which describes a stone that has been driven into the ground, and which is used to indicate a frontier or boundary.
Hang out for locals. Food was below average and pilgrims being there almost seemed like an afterthought. Standard metal bunks w. lockers. Bathroom wasn't clean and had mold, the rooms dingy, and walls thin. Found a bedbug but may not have originated there.


text:
Q: UIImagePickerController in iPhone OS 3.0 I am using iPhone OS 3.0 SDK.
My requirement is that I want to get the image from the photo albums library and display it on an image view.
I am using the UIImagePickerController  for that.
But the problem is the - (void)imagePickerController:(UIImagePickerController *)picker didFinishPickingImage:(UIImage *)imageeditingInfo:(NSDictionary *)editingInfo  delegate method is deprecated in iPhone OS 3.0 ,
Is there any alternative for getting the Image from the UIImagePickerController.
All suggestions are highly appreciated.
Thanks...

A: use this delegate method of UIImagePickerController in your implementation file.
-(void)imagePickerController:(UIImagePickerController *)picker didFinishPickingMediaWithInfo:(NSDictionary *)info {
    [picker dismissModalViewControllerAnimated:YES];
    imageView.image = [info objectForKey:@"UIImagePickerControllerOriginalImage"];
}

and don't forget to modify your header file with these two protocols
@interface photoAppViewController : UIViewController < UIImagePickerControllerDelegate,UINavigationControllerDelegate >

A: Speaking of 3.0 here would break your and my NDA with Apple. However I can suggest that you look at the relevant header files (mdfind didFinishPickingImage | grep 3.0 will find what you need quickly).

A: Some one posted me the answer as below.
In UIImagePickerController.h you can see that there ist a method you
can use:
- (void)imagePickerController:(UIImagePickerController *)picker
didFinishPickingMediaWithInfo:(NSDictionary *)info;

The documentation does not show this method it is only in the .h file.
but I am still not getting the above method in the .h file


text:
What Goes Around Comes Around? Rewards as Strategic Assets in Crowdfunding
Carina Thürridl, Bernadette Kamleitner
Marketing und KonsumentInnenforschung
In crowdfunding, rewards can make or break success. Yet reward design, choice, and planning still occur based on availability rather than strategy. To address this challenge, this article provides an empirically derived crowdfunding reward toolbox offering guidance in strategically selecting rewards. Based on a large scale analysis of successful and unsuccessful Kickstarter projects, this article classifies rewards that are currently offered along eight dimensions. It identifies emerging patterns and derives five strategic core tools and two add-on tools. Finally, it delivers exploratory insights into the relative effectiveness of different tools that can facilitate decision making and strategic planning for entrepreneurs and individuals who plan to launch a crowdfunding project and who seek ways to reward their supporters.
https://doi.org/10.1525/cmr.2016.58.2.88
502019 Marketing
10.1525/cmr.2016.58.2.88Lizenz: Nicht angegeben
http://cmr.berkeley.edu/search/articleDetail.aspx?article=5813
Thürridl, C., & Kamleitner, B. (2016). What Goes Around Comes Around? Rewards as Strategic Assets in Crowdfunding. California Management Review, 58(2), 88 - 110. https://doi.org/10.1525/cmr.2016.58.2.88
Thürridl, Carina ; Kamleitner, Bernadette. / What Goes Around Comes Around? Rewards as Strategic Assets in Crowdfunding. in: California Management Review. 2016 ; Jahrgang 58, Nr. 2. S. 88 - 110.
@article{5758e817cca34caaa5c7eb062fea718a,
title = "What Goes Around Comes Around? Rewards as Strategic Assets in Crowdfunding",
abstract = "In crowdfunding, rewards can make or break success. Yet reward design, choice, and planning still occur based on availability rather than strategy. To address this challenge, this article provides an empirically derived crowdfunding reward toolbox offering guidance in strategically selecting rewards. Based on a large scale analysis of successful and unsuccessful Kickstarter projects, this article classifies rewards that are currently offered along eight dimensions. It identifies emerging patterns and derives five strategic core tools and two add-on tools. Finally, it delivers exploratory insights into the relative effectiveness of different tools that can facilitate decision making and strategic planning for entrepreneurs and individuals who plan to launch a crowdfunding project and who seek ways to reward their supporters.",
keywords = "#inspiration, #inspiration",
author = "Carina Th{\"u}rridl and Bernadette Kamleitner",
doi = "10.1525/cmr.2016.58.2.88",
pages = "88 -- 110",
journal = "California Management Review",
publisher = "Haas School of Business",
Thürridl, C & Kamleitner, B 2016, 'What Goes Around Comes Around? Rewards as Strategic Assets in Crowdfunding', California Management Review, Jg. 58, Nr. 2, S. 88 - 110. https://doi.org/10.1525/cmr.2016.58.2.88
What Goes Around Comes Around? Rewards as Strategic Assets in Crowdfunding. / Thürridl, Carina; Kamleitner, Bernadette.
in: California Management Review, Jahrgang 58, Nr. 2, 2016, S. 88 - 110.
T1 - What Goes Around Comes Around? Rewards as Strategic Assets in Crowdfunding
AU - Thürridl, Carina
AU - Kamleitner, Bernadette
N2 - In crowdfunding, rewards can make or break success. Yet reward design, choice, and planning still occur based on availability rather than strategy. To address this challenge, this article provides an empirically derived crowdfunding reward toolbox offering guidance in strategically selecting rewards. Based on a large scale analysis of successful and unsuccessful Kickstarter projects, this article classifies rewards that are currently offered along eight dimensions. It identifies emerging patterns and derives five strategic core tools and two add-on tools. Finally, it delivers exploratory insights into the relative effectiveness of different tools that can facilitate decision making and strategic planning for entrepreneurs and individuals who plan to launch a crowdfunding project and who seek ways to reward their supporters.
AB - In crowdfunding, rewards can make or break success. Yet reward design, choice, and planning still occur based on availability rather than strategy. To address this challenge, this article provides an empirically derived crowdfunding reward toolbox offering guidance in strategically selecting rewards. Based on a large scale analysis of successful and unsuccessful Kickstarter projects, this article classifies rewards that are currently offered along eight dimensions. It identifies emerging patterns and derives five strategic core tools and two add-on tools. Finally, it delivers exploratory insights into the relative effectiveness of different tools that can facilitate decision making and strategic planning for entrepreneurs and individuals who plan to launch a crowdfunding project and who seek ways to reward their supporters.
KW - #inspiration
UR - http://cmr.berkeley.edu/search/articleDetail.aspx?article=5813
U2 - 10.1525/cmr.2016.58.2.88
DO - 10.1525/cmr.2016.58.2.88
JO - California Management Review
JF - California Management Review
Thürridl C, Kamleitner B. What Goes Around Comes Around? Rewards as Strategic Assets in Crowdfunding. California Management Review. 2016;58(2):88 - 110. doi: 10.1525/cmr.2016.58.2.88


text:
Q: INSERT in Stored Procedure called via JDBC I have an MSSQL Server 2008 (Express) set up.
In my database I have a set of tables and a stored procedure.
What I want to achieve is get any changes that have been made to an existing table, and return them at the end of the procedure. The stored procedure I have created works fine when I run it locally within MSSQL Management Studio.
However, when I call the procedure through a JDBC connection certain parts of the procedure seem to have not completed.
The summary of what I'm trying to do is as follows:
1) Put a snapshot of the data contained in CurrentTableA into #CurrentShotA (temporary table)

2) Compare #CurrentShotA with PreviousTableA

3) Insert differences into #TempTableB
(this equates to new rows or altered rows in #CurrentShotA)

4) Empty PreviousTableA

5) Insert contents of #CurrentShotA into PreviousTableA

6) Select * from #TempTableB (return all new rows and changes)

Step 6 returns the data correctly the first time it is called via JDBC.
When the procedure is called the second and subsequent times it is clear that step 5 has not completed as expected. PreviousTableA is always empty when it should contain a snapshot of the old data.
Question is why does the procedure work properly when called with in MSSQL Management studio but not when I call it via JDBC?
CREATE PROCEDURE [dbo].[getUpdatedSchedules]
AS
BEGIN
-- SET NOCOUNT ON added to prevent extra result sets from
-- interfering with SELECT statements.
SET NOCOUNT ON;

-- Check of the temporary table exists, delete if it does
        IF OBJECT_ID('#TempTableB','U')IS NOT NULL
        begin
            drop table #TempTableB
        end

        -- Force the creation of the temporary tables quickly
        select * into #TempTableB from dbo.CurrentTableA where 1=0
        select * into #CurrentShotA from dbo.CurrentTableA where 1=0

        -- Get the differences between schedules and put into #TempTableB
        insert #CurrentShotA select * from dbo.CurrentTableA
        insert #TempTableB select * from #CurrentShotA
        except select * from dbo.PreviousTableA

        TRUNCATE TABLE dbo.PreviousTableA
        insert dbo.PreviousTableA select * from #CurrentShotA
        select * from #TempTableB
    END
GO

I'm new enough to stored procedures and MSSQL configuration so I have considered that it might be a permissions issue. I login to MSSQL Studio using SQL authentication that is not linked to a windows account and the procedure runs as normal so I don't think it's permissions.
I hope my explanation and question is clear enough. I'd appreciate any thoughts or suggestions as to what I am doing wrong.

A: There's no need to check if #TempTableB exists since it will be dropped automatically once the procedure finishes executing, just as the other temp tables are dropped automatically; perhaps you expect these tables to have data on subsequent calls to the proc and that's why you think it doesn't work when you call it from Java?
When you execute these SQL statements from SSMS they may have data in them since it's all the same database session, but that's not the case when called using JDBC.


When I'm on the speaking circuit and talking about Peterson Garden Project and Chicago Victory Gardens, there is always someone who says they remember their parent's WW2 Victory Garden. I love hearing of memories that have lasted so long and are usually quite powerful and touching. I always ask if photos exist and, sadly, they rarely do.


Low price guarantee. We are an official tour organizer agency on Lake Garda. Free cancellation till 24 hours prior the departure time! No penalties fee.
Our excursions on Lake Garda are provided by new and comfortable coaches ! We do not use old and not-recommended buses. We want to give the customer the right security to better face his vacation.
LikeGarda.com initially housed only a few classic excursions on Lake Garda. With the passage of time we have seen the growth of new products that could give the usual customer something different!
We are a young team with a travel agency with over 40 years of experience on Lake Garda behind us with the passion for our territory and with the aim of giving our customers unforgettable stays!
Emma was fantastic and we learned so much from her. The trip was outstanding in that we went to three vineyards and tasted wine as well as took a historical tour of Soave and had time for lunch. I did this trip on my own a few years ago and cannot believe how much I missed on my own. Emma gives great suggestions for lunch and what to see. Loved this trip and the wine tasting too!
This tour was absolutely amazing!! My husband and I love it and this place was on our bucket list. The tour guide was so nice and spoke English very well. Venice is breath taking… this is a must do!!
This trip was pretty amazing actually. My girlfriend and I enjoyed Verona. Sylvia, our guide and driver was very knowledgeable and also a delight on the journey. She catered to our every need and was very generous with the amount of time so that we had enough time to truly explore the city. This is easily one of the best tours to visit Verona!


text:
Parker salutes Cottagers after rare win
14th April 2019, 03:24 by Michael Holland
Scott Parker paid tribute to the character shown by his Fulham players after they picked up a rare victory against Everton yesterday.
The Whites have struggled all season and an immediate return to the Sky Bet Championship was confirmed with defeat at Watford two weeks ago.
But they picked up just a fifth league win of the season with a fine performance and a well-deserved 2-0 win over a poor Everton outfit.
Captain Tom Cairney opened the scoring with just the second Premier League goal of his career and his first since scoring against Everton for Hull in March 2010 before Ryan Babel wrapped up a rare win for the home side.
Aleksandar Mitrovic passed up a number of first-half opportunities, but Fulham struck twice in the second half to pick up their first victory since January and a maiden win for caretaker boss Parker, who praised his squad after the game.
"If ever the focus was on this team it was now. We realised the challenge ahead, staying in the Premier League, was tough," he said.
"But once we were relegated it would have been easy and questions have been asked of me, 'Are your players still up for the fight or on the beach?'
"Ultimately they answered those questions. For me, the fans and everyone else that character was brought into play today and certainly the players proved people wrong and showed real fight and determination."
Michael Holland is a reporter with over two decades of journalism experience. A Bolton fan, Michael often writes football articles, as well as having a strong knowledge of golf, cricket and Australian sports.
14:09 Ravel Morrison has signed for Sheffield United on a one-year contract after trial period.⌁
13:55 John Gosden says Too Darn Hot to step back up to a mile for Sussex Stakes at Glorious Goodwood.⌁
2 A Villa 0 0 0 0 0 0 0 0
4 Brighton 0 0 0 0 0 0 0 0
7 C Palace 0 0 0 0 0 0 0 0
9 Leicester 0 0 0 0 0 0 0 0
11 Man City 0 0 0 0 0 0 0 0
12 Man Utd 0 0 0 0 0 0 0 0
13 Newcastle 0 0 0 0 0 0 0 0
14 Norwich 0 0 0 0 0 0 0 0
15 Sheff Utd 0 0 0 0 0 0 0 0
16 Soton 0 0 0 0 0 0 0 0
17 Tottenham 0 0 0 0 0 0 0 0
19 West Ham 0 0 0 0 0 0 0 0
20 Wolves 0 0 0 0 0 0 0 0
More Fulham
Fulham snap up winger
Fulham have completed the signing of Wolves winger Ivan Cavaleiro, who joins the club on a season-long loan deal.
Roma considering move for Cottagers flop
Roma have expressed an interest in signing Fulham midfielder Jean Michael Seri this summer, according to his agent Franklin Mala.
Fulham eye Chelsea star
Chelsea's talented young midfielder Trevoh Chalobah is a loan target for Fulham.
McLean hoping injured duo recover soon
Kenny McLean says injuries are inevitable during pre-season but he hopes Norwich duo Ben Godfrey and Louis Thompson recover soon.
Lindelof dismisses agent's Red Devils exit hint
Victor Lindelof has spoken out to insist that he is "very happy" at Manchester United despite his agent linking him to Barcelona.
Farrell targets WC redemption
Owen Farrell says England's failure four years ago is driving the squad on ahead of the 2019 Rugby World Cup.
Cooney wants Premier action after Clarets switch
Burnley's Under-23 signing Ryan Cooney has set his sights on playing in the Premier League after joining on a 12-month deal from Bury.
Travers eager to kick on at Vitality
Goalkeeper Mark Travers is excited for the future with Bournemouth after committing to a new "long-term" contract.