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CIRCULAR, CIR/IMD/DF-1/19/2012, dated July 25, 2012
All Registered Merchant Bankers
All Recognized Stock Exchanges
1. SEBI had notified SEBI (Issue and Listing of Debt Securities) Regulations in 2008 specifying norms for public issue of debt securities and privately placed listed debt securities.
2. With respect to public issue of debt securities, there is currently no specified standard format for the Application Form and Abridged Prospectus. This has resulted in different application forms and abridged prospectus being used in public issues of debt securities.
3. In order to standardize the Application Form and Abridged Prospectus for public issue of debt securities, the existing forms and abridged prospectus were discussed and deliberated upon with market participants. Based on the discussions, the structure, design, format, contents and organization of information in the Application Form and Abridged Prospectus have been standardized and made uniform for public issues of debt securities.
Application Form
4. The following shall be applicable with respect to the application form to be filled up by the investor:
a) All Application forms shall be printed in A4 size sheet. The illustrative format of Application Form that shall be used for Resident and Non-Resident Investors (NRI), are placed at Annexure A and B respectively. It may be noted that certain sections in the form are filled only for illustrative purposes.
b) No change shall be carried out in spacing, placement or in data fields in the Application Form except for the following:
i. For issues offered only in dematerialized form, the sections pertaining to physical applications may be removed.
ii. Under Point No. 5 in application form, the number of columns for providing different series details is illustrative and may vary depending on the terms of the issue.
iii. Investor Categories and sub-categories may vary depending on the issue.
iv. Details to be provided under issue structure may vary depending on the terms of the issue.
v. KYC documents required may vary depending on the terms of the issue.
vi. The declaration pertaining to application in physical form may be removed if the issue is offered only in dematerialized form.
c) In case the issue is not offered to NRI investors, the NRI specific form may not be printed.
Abridged Prospectus
5. The following shall be applicable with respect to the abridged prospectus annexed to the application form:
a) The abridged prospectus shall be printed in A4 size sheets. The information shall be provided under the abridged prospectus as given at Annexure-C hereto.
b) The Abridged Prospectus shall be printed:
i. In Times New Roman font,
ii. in a font size of not less than 10,
iii. with a line spacing not less than 1.00 lines
iv. and normal character spacing with 100% scale and no condensation.
c) A larger font size may be used, if required, for different heads of information. All major heads shall be in uppercase and bold and in boxes. The first level subheads shall be in bold and in boxes. The other levels of sub-heads shall be bold and underlined.
d) The numbering shall be either continuous or with different types of numbering for different heads/ sub-heads.
e) The application form shall be so positioned that on the tearing-off of the application form, no part of the information given in the abridged prospectus is mutilated.
f) The order of the contents in the abridged prospectus shall not be changed.
g) Tabular formats and pointers may be used wherever possible for efficient understanding. Instructions for filling up the form, payment instructions and risk factors shall be in pointers and every pointer shall be in a new line.
h) The top of every page in the abridged prospectus shall have a colored strap in bold letters incorporating the statement
i) Under the sections 'any other information', any information which is important for the investor but has not been included in the other heads may be included.
j) Risk factors shall be so provided that they convey the risks associated with the issue briefly.
k) A reference may be made to the prospectus wherever necessary.
6. The issuer and all the concerned intermediaries are directed to comply with the instructions contained in this circular effective from 30 days to the date of this circular.
7. This circular is issued in exercise of powers conferred under Section 11(1) and section 11A of the Securities and Exchange Board of India Act, 1992 read with Regulation 31(1) of SEBI (Issue and Listing of Debt Securities) Regulations, 2008.
8. This circular is available on SEBI website at http://www.sebi.gov.in/ under the category "Legal Framework" and "Corp Debt Market".
Yours faithfully,
Maninder Cheema
Deputy General Manager
Investment Management Department
Tel No.022-26449754
Email id – firstname.lastname@example.com
Click here to download the complete text of the above Circular in PDF Format- CIRCULAR, CIR/IMD/DF-1/19/2012, dated July 25, 2012.
Source: Securities and Exchange Board of India.


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56 comments to "The Doctor and the Monkey"
Hi! I just wanted to say "Thanks!" for all your articles, especially the ones for beginners. It's so hard to find Chinese content for beginners, even in 2013! I can't believe I'm reading children stories… Yet, I am very grateful for these. So, 谢谢你!
I have the same opinion of jmtahk previous comment. Also a beginner that can with a little dificulty read beginner texts, so that they are very appropiate. Thanks for posting this material.
Bye bye from Málaga Spain.
I saw some typos…like 了liao with了 le。
Fiona, these are not typos. Annotations are done automatically by a program. 了 can be pronounced either as le or as liǎo depending on the context. That's why you see both pronunciations on the pop-up.
Well。。。 maybe next time I will see some more typos。
Fiona you're whack.
hi, i just want whoever made this comment to know that i was a child when i made this comment. i recently got a notification and looked through my old to see this here. imagine if i had seen that all those years ago, instead, let me leave this : fuck you anonymous asshole. thanks !!
hi, i just want whoever made this comment to know that i was a child when i made this comment. i recently got a notification and looked through my old comments to see this here. imagine if i had seen that all those years ago, instead, let me leave this : fuck you anonymous asshole. thanks !!
Hi Kendra,
I followed a link about Zhajiangmian which led me to your site and exploring further, I found your Chinese reading practice articles. So interesting! Our whole family is taking Chinese lessons via Skype so finding extra material is always exciting. Thank you for all your work!
Thanks so much!! this is really helpful
I'm a Vietnamese person. what a good thing you have given me! It is useful for not only practicing reading chinese but also useful for reproducing more inferences about the real life. Thank you very much!
Thank you very much! It was very useful
really helpful, im learning chinese and it is great. I love that you have also put in the translations. very happy with this website. Thankyou very much
a learning chinese and these stories are helping me ….thanx alot
a learning chinese and these stories are helping me ….thanx a lot
Thank you so much for taking the time to share these stories! To find something both beginner and enjoyable is rare. I really appreciate your efforts! Really helping me with reading, vocabhlary, colloquialisms and culture!
These are pretty good, I never learned simplified so sometimes it can be tough for me, but I figure the more I read the better acquainted I will become with simplified characters. This is exactly the type of site I was looking for. I also hope to find some good books to read, or news articles, or something to supplement my vocabulary. Keep up the good work!
Thank you very much about all of stories….
Best blog for practicing Chinese reading skills… Best blog ever!
thx so much
hope that monkey don't were a doctor.
Can you add pinyin? P.S(I don't know some of the words)
Many thanks for your postings!!! Started learning with the mokney story But can't wait till I start learning the rest .
I have one question on this text: are you sure the second sentence shouldn't be "正好大夫不在,衣服也落了在房间内。", with 了 and 在 in this order? I can't find a compound verb like "落在" anywhere, so this is a bit confusing to me.
thank you for all your materials. you're great.
Just in case this somehow wasn't you who asked this question in this forum, here's the answer to your question. =D
Not enough tentacles 0/10
Not enough dicks msg me if u hrny
Funny little story. Thanks.
Gee, I like this story. I will try to retell it to my brothers. They will like it too. It is a very funny monkey.
I wish i can send a photo
So helpful. Thanks a lot
Wow I hope no one was like actualy sick or something like a broken leg. So at the end of the story when it says monkey got his own "white lab clothes, does it mean he was already grown up or is he still a kid? Anyhow thanks again. P.S. I've read every single one before this one and there all great story's so THANKS ONCE AGAIN!!!!! whoooo!! => =]
Really good story.
love the story
Thank you for the good story! It definitely helps my Chinese writing skills! (I'm writing them down to improve my handwriting)
Where are you getting those stories from anyway?
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Thanks for this. I'm reading this with my 2nd grade class. It's fun showing them the text in Chinese; then seeing it written in English. The kids are having fun writing words in both languages.
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subset: commoncrawl


text: Apricot Lane boutique offers contemporary fashion influenced by west coast trends mixed with east coast style. We feature a great mix of your favorite brands along with up-to-date styles from new designers. You won't see the items we carry just anywhere. We seek out unique finds and update our inventory weekly. In addition, Apricot Lane offers friendly customer service from our fashion savvy associates who are here to help you find just the right style and fit for you.


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more pages
Using a router as a firewall
Gateway routers cost little more than a good software firewall package (the one shown below cost less than £40). Make sure you get a model that supports your type of internet connection. The one featured here supports a conventional v90 modem, as well as ISDN and cable/DSL modems.
As a bonus you get a four port hub for home networking and the means to share an internet connection without using a software application like Microsoft's Internet Connection Sharing. For brief manual details click here
The router is conveniently small and configuring it through a browser interface is straightforward.
Copyright © 2008 [Fen Tyler]


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Serverless architecture is one of the most sought after technologies today in Software Architecture world. It refers to applications where server-side logic is run in stateless containers that are event-triggered, ephemeral and fully managed by a third-party service known as Backend as a Service "Bass" or Function as a Service "Fass". Most of the cloud vendors including Amazon, Google and Microsoft are heavily invested in their Serverless offerings. Despite the name, it does not actually involve running code without servers. The name "serverless computing" is used because the application owner does not have to purchase, rent or provision servers or virtual machines for running the serverless backend.
7 months, 3 weeks agoCisco Simplifies Kubernetes Container Deployment With Microsoft Azure Collaboration
Microsoft's Azure Kubernetes Service (AKS) has been added to the Kubernetes managed services that..
8 months agoServerless With Knative - Mete Atamel
When you build a serverless app, you either tie yourself to a cloud provider, or you end up build..
8 months, 1 week agoGoogle to Acquire Elastifile
The combination of Elastifile and Google Cloud will help businesses bring traditional workloads i..
Mike Melanson , 8 months, 1 week agoOpenwhisk Serverless Graduates Apache, Looks Ahead to Knative, Envoy And More
This week, the open source serverless project Apache OpenWhisk has graduated from an incubating p..
Ron Miller , 8 months, 1 week agoStackery Lets AWS Lambda Developers Debug Their Serverless Programs Locally on a Laptop
Serverless developers have always faced a steep challenge when it comes to writing code on their ..
8 months, 1 week agoGitlab And Google Webcast - Running Containerized Applications on Modern Serverless Platforms
In this webcast, we'll walk through some of the benefits and challenges of using cloud-vendor-spe..


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Investing Reading List
I am a big proponent of not reinventing the wheel and that means learning about those who have previously mastered the art of investing. I am often asked who I think these masters are and for a list of books about them. After sending individual emails and paper lists to people through the years, I finanlly decided to put it up somewhere permanent and I have done my best to break them up into relevant sections, give short descriptions and reasons why you should read them.
If you only read 4 books about investing, these are the ones to read. Intelligent Investor is a classic of value investing, Reminiscences of a Stock Operator is a classic of trading, Common Stocks and Uncommon Profits is the classic of growth investing and it can't hurt to also learn straight from Warren Buffett who is one of the greatest investors of all time.
The Intelligent Investor
Useful Topics Introduced
- Draws a distinct line between investing and speculation, where investment requires both safety of principal and adequate return, while speculation does not adequately protect principal.
- Ownership of equity should be regarded first and foremost as a share of ownership of a business.
- Stock owner should not be concerned what Mr. Market believes in the short-term as true value in the long run will be reflected in its stock price
- When a company is available on the market at a price which is a discount to its intrinsic value, a "margin of safety" exists, which makes it suitable for investment.
Reminiscences of a Stock Operator
Useful Topics Introduced
- "It never was my thinking that made the big money for me. It always was my sitting."
- "There is nothing new in Wall Street. There can't be because speculation is as old as the hills. Whatever happens in the stock market today has happened before and will happen again."
- "Of course there is always a reason for fluctuations, but what the tape does not concern itself with the why and wherefore. It doesn't go into explanations. The reason for what a certain stock does today may not be known for two or three days, or weeks, or months. But what the dickens does that matter? Your business with the tape is now - not tomorrow. The reason can wait. But you must act instantly or be left."
- "A stock operator has to fight a lot expensive enemies within himself."
- "I never argue with the tape. Getting sore at the market doesn't get you anywhere."
- "The game of speculation isn't all mathematics or set rules, however rigid the main laws may be."
Common Stocks and Uncommon Profits
Fisher's 15 Points Checklist
- Is there sufficient market potential to increase sales?
- Is management developing new products or processes?
- How efficient is the R&D effort?
- Is there an above average sales organization?
- Does the company have a high profit margin?
- Is the profit margin improving?
- Does the company have stable labor relations?
- Does the company have stable executive relations?
- Does the company have a deep bench of experienced managers?
- Are the companies cost and audit controls sufficient?
- Are there peculiar industry conditions involved?
- Does the company take a short or long term view?
- Does continued growth require additional capital raising?
- Is management transparent to investors?
- Can management be trusted?
Berkshire Hathaway Letters to Shareholders
There are a couple of reasons to read this book:
- He is one of the greatest investors of all time, with a compounded annual return of 19.7% from 1965 to today.
- While he started out as a straight value investor in the mold of Graham, overtime he amends his investing philosophy to also look at exceptional companies at a reasonable price.
- By reading 47 years of annual reports annual reports you get a sense of how much has changed since 1965 in business and investing, as well as what hasn't.
- Lots of folksy wisdom, "You don't see who is swimming naked until the tide goes out"
- He's now the second richest man in the world, and the richest takes a great deal of investment advice from him


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Articles Tagged 'Aer Lingus Regional'
Ireland sees strong capacity growth over past three years, led by international expansion; Ryanair remains top carrier
The number of seats available on services to, from and within the Ireland increased by 5.0% from 2016 to 2017. anna.aero has been digging out the top trends in the country's domestic and international links over the past 10 years, including the biggest airline and destination market movers.
Singapore Airlines converts its Singapore – Manchester – Houston Intercontinental route to an A350 operation
In this week's Network Planning Community News, Aruba celebrates the arrival of JetBlue Airways' new connection from Fort Lauderdale while United Airlines toasts 25 years of serving Madrid. More news also from Cornwall Airport Newquay, Luxembourg, Sao Paulo Guarulhos and Manchester airports.
Aer Lingus adds three new routes from Cork this summer; Düsseldorf, Leeds Bradford and Southampton raise network to 21 destinations
Aer Lingus is the biggest airline at Ireland's second busiest airport. We look at how the airline's network has fluctuated since 2006, which are currently its busiest routes by ASKs and on which routes Ryanair competes head-to-head.
Aer Lingus Regional adds to Ireland – UK market
Aer Lingus Regional starts a connection between Cork and Leeds Bradford while also resuming a link between Shannon and Edinburgh.
Aer Lingus Regional connects Cork to Southampton
Aer Lingus Regional begins a five times weekly service between the Irish and UK airports.
Aer Lingus Regional debuts Dublin to Newquay route
Aer Lingus Regional now links Dublin to Newquay with thrice-weekly flights, using Stobart Air's ATR 72s.
Doncaster Sheffield Airport celebrates 10 years of flights; passenger numbers up 30% in Q1 as Wizz Air grows and Aer Lingus arrives
This UK airport, known as Robin Hood Airport, handled over one million passengers in 2007. Since then demand has slipped, but more recently grew by 5% in 2014. Thomson Airways and Wizz Air are the busiest airlines at the airport with high seasonality.
Aer Lingus Regional starts East Midlands route
Aer Lingus Regional resumes flights between Dublin and East Midlands. Competes against Ryanair.
Jönköping Airport receives Cake of the Week award for bmi regional
In this week's Network Planning Community News, Aer Lingus Regional announces a new route from Doncaster Sheffield to Dublin starting on 29 May, and London Gatwick Airport celebrates St Piran's Day – Cornwall's national day. More news from Birmingham, Sao Paulo Guarulhos, Phoenix-Mesa, Bahrain, Bristol and TAV Airports.
Aer Lingus Regional replaces Flybe on PSO routes from Donegal
Aer Lingus Regional starts flights from Donegal to Dublin and Glasgow.
Aer Lingus Regional returns to Leeds Bradford from Dublin
Aer Lingus Regional joins Ryanair in serving the Dublin-Leeds Bradford sector with 13 weekly services, using its ATR 72s.
Vote for the best of 10 Fire Truck Water Arches; Winter Season Launches Part 1
The start of the W14/15 season sees a lot of the world's airports pulling out all the stops in terms of new route marketing ‒ and that means lots of fire truck water arches (FTWAs). This week, we give you, the reader, the chance to select the best of the 10 FTWAs we have been […]


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If you want one simple way to understand what's happening in American politics before Tuesday's election, Laura Stoker, a UC Berkeley associate professor of political science, has your answer: The generic ballot.
"It's probably the number one best predictor of the midterm outcomes," said Stoker, who specializes in understanding changing political attitudes and behavior.
The generic ballot is a simple question put to voters across the country almost daily: If the congressional election were held today, would you vote for the Democrat or the Republican? Aggregate all those results, as sites like FiveThiryEight do, and you can get a pretty good sense of voter sentiment, Stoker said.
Structural disadvantages for Democrats like super concentrations of liberal voters in urban areas and gerrymandering, mean that Republicans will likely retain control of the House if Democrats get 54 or 55 percent of the two-party vote. But if they get more, the scales can start to tip in a dramatic way.
Election 2018
Professor Robert Reich doesn't think Dems can take back the House
"Every percentage point above seven or maybe eight in the Democratic vote advantage has an increasing consequence for the balance of power in the House," she said. "More votes bring more seats, but at a 6- to 7- point advantage, it starts to speed up a little bit. In the 8 point and above range, every additional 1 percent should bring well more than 1 percent of the seats."
(The current estimate on FiveThirtyEight is that Democrats lead by 8.5 percentage points.)
But things are never that simple, Stoker adds. A big source of uncertainty is who will actually show up at the polls. Pollsters always struggle to estimate turnout, especially as both Democrats and Republicans make pitches designed to encourage unlikely voters — the ones polls sometimes ignore — to vote.
"All signs point to higher turnout in 2018, but the real question is whether that turnout will advantage one party or another. Shifts in the party's demographic bases are adding to the uncertainty," Stoker said.
Democratic voters are getting younger and Republican voters are older, and older voters are more likely to vote. But at the same time, highly educated voters are increasingly supporting Democratic candidates while less educated voters are supporting Republicans, Stoker said.
On top of that, growth in the gender gap since 2016 adds uncertainty. Are the women seemingly turning against President Trump and the Republican Party likely to vote —and vote Democratic — on Election Day?
"That's one of the big question marks for me," Stoker said.
Stoker, and an array of other experts, will discuss Tuesday's election during a Friday panel, "Blue Wave or Red Wall?" which runs from noon to 1:30 p.m. in 820 Barrows Hall. In advance of that talk, Berkeley News sat down with Stoker to discuss what matters – and what doesn't – five days before the midterm election.
Let's talk about the generic ballot. Why is that so important?
It's probably the number one best predictor of the midterm outcomes. In particular, we know that Democrats in general face a structural disadvantage because of two things. One is the way that Democrats are concentrated in districts and states, and the way district boundaries are drawn, i.e. gerrymandering. We know that they need a certain advantage to overcome that. That's why you always hear that they need anywhere from a 4 to 7 percentage point advantage in the generic ballot to even win 50 percent of House elections.
This election is deeply nationalized."
– Laura Stoker
This election is deeply nationalized. For that reason, Trump's approval rating is also a great predictor of election outcomes, more so than say what Reagan's approval was or what Clinton's approval was.
Exactly what's going to happen depends on how big that Democratic advantage is in voter turnout. And since our polls are national and there are 435 races, it's possible for any number of things to happen. Democrats could win by 5 percent of the vote and still not get a majority depending on exactly where those votes are in the 435 districts.
Every percentage point above seven or maybe eight in the Democratic vote advantage has an increasing consequence for the balance of power in the House. As you go from 50/50 to a 5- to 6-percentage-point Democratic advantage, the seat gain is linear, but at a 6- to 7-point advantage, it starts to speed up a little bit. At the 8 point and above range, every additional 1 percent brings well more than 1 percent of the seats.
Can the generic ballot tell us anything about the Senate or the races for governor?
No. Everything we know about Senate races comes from statewide polling. Same with governors. The generic ballot asks about House races and it works because there are House elections nationwide.
I think a lot of people feel burned by what they thought were bad polls in the 2016 race. Are you thinking about that? Why can we trust polls in 2018?
The claim that the 2016 national polls were wrong is exaggerated. They had Clinton ahead and she won by three million votes! Still, people give too much attention to national polling. National polls are not good when the election of a president depends on an electoral college victory, on what is happening in the states. We need more high quality polls in the 50 states, or at least the battleground states.
A lot of uncertainty doesn't come from polling being broken but from having no clue who's going to vote. It's about this turnout model. Remember when any poll is reporting their results they're doing it for registered voters or likely voters. And there's always this big gap between your guess as to who's going to vote and who actually votes. If you've got a bad likely voter model you're going to have bad predictions.
We have very little basis for making guesses about this. It turns out that early voting is not terribly predictive of anything, though it is up this year compared to the last midterm election. Pollsters routinely ask about voter enthusiasm in order to glean whether one or another party is going to have a turnout advantage. There's no question that enthusiasm is up. And there's not a huge Democratic advantage there. There's a bit of a one, but nothing huge.
What are you watching in terms of voter behavior and long-term trends? What could we learn on Tuesday?
There has been a reorganization of the party bases in terms of the highly educated and the less educated. The less educated Americans are increasingly gravitating toward the Republicans and the more educated Americans are increasingly gravitating toward the Democrats.
That is a fundamental change that could erase the long-term disparity in turnout between Republicans and Democrats. Democrats have almost always been disadvantaged by lower turnout of their base than the Republicans. That difference is typically much bigger in midterm elections — though less so when Republicans are in power, as now.
But my guess is that that's changing and that means the Democratic disadvantage might be a thing of the past.
Another thing I'll be watching is the voting behavior of young people. The general pattern has been for young people to come into the electorate and be more supportive of whichever party holds the presidency. But, young people started gravitating to the Democrats in 2006, under Bush, and grew even more pro-Democratic under Obama. What's very unusual is that has continued under Trump. If anything, we're seeing an exacerbation of the age divide under Trump. That's new.
I'm also going to be paying attention to whether the Democrats succeeded in mobilizing young people to get out and vote. Obama did in 2008. It can be done.
We talk a lot about suburban women voting against Trump.
That's one of the big question marks for me. We've seen in the last three years that there's a massive growth in the gender gap between Democrats and Republicans.
Women make up 50 percent of the population and often make up more than 50 percent of the voters. When you start seeing a massive shift in that gender divide, the question is whether we are seeing a new era of party dominance.
What that could be suggesting is maybe a 5-point edge in the starting point for Democrats, or maybe even a 6-point edge. Going back to that generic ballot, if the starting point isn't 50/50, but the starting point is 55 to 45 or something like that, that's a big change. And I think that might be happening.
Reporters interested in speaking with Laura Stoker can reach Will Kane at email@example.com


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5 Things To Do with Chalk
Want to get your silverware sparkling and your whites bright? Chalk it up! Here's how to put common sidewalk chalk to good use throughout the home.
5 New Household Uses for Chalk
Did you know…
The first "street painting" took place in sixteenth century Italy, when artists began using chalk to make drawings on the pavement.
Use Chalk to Keep Silver from Tarnishing
You love entertaining with your finest silverware, but polishing it before each use is another story. Put one or two pieces of chalk in the drawer with your good silver; it will absorb moisture and slow tarnishing. Put some in your jewelry box to delay tarnishing there, too!
Use Chalk to Remove Grease Spots
Rub chalk on a grease spot on clothing or table linen and let it absorb the oil before you brush it off. If the stain lingers, rub chalk into it again before laundering. To get rid of ring-around-the-collar stains, mark the stains heavily with chalk before laundering. The chalk will absorb the oils that hold dirt in.
Use Chalk to Polish Metal and Marble
To make metal shine like new, put some chalk on a damp cloth and wipe. (You can make chalk dust by pulverizing pieces of chalk.) Buff with a soft cloth for an even more brilliant finish. Wipe marble with a damp, soft cloth dipped in powdered chalk. Rinse with clear water and dry thoroughly.
Use Chalk to Keep Tools Rust-Free
You can eliminate moisture and prevent rust from invading your tool box by simple putting a few pieces of chalk in the box. Your tools will be rust-free-and so will the toolbox.
Use Chalk to Reduce Wardrobe Dampness
Tie a dozen pieces of chalk together and hang them up in a damp wardrobe. The chalk will absorb moisture and help prevent mildew, but remember to replace the chalk with a new bundle every few months.
Related links:
5 Things to do With Toothpaste
5 Things to do With Beer
5 Things to do With Bananas


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According the the U.S. Food and Drug Administration (FDA), General Mills announced today a voluntary national recall of five-pound bags of its Gold Medal Unbleached Flour with a better if used by date of April 20, 2020. The recall is being issued for the potential presence of Salmonella which was discovered during sampling of the five-pound bag product. This recall is being issued out of an abundance of care as General Mills has not received any direct consumer reports of confirmed illnesses related to this product.
This recall only affects this one date code of Gold Medal Unbleached Flour five-pound bags. All other types of Gold Medal Flour are not affected by this recall.


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Welcome to
of BOOST Cafe!
We are pleased to announce the BETA release of BOOST Cafe!
You are the first exclusive users of the BOOST BETA and we rely on you for important feedback. Something not working? See an opportunity for us to do better? Let us know! Email email@example.com.
What is BOOST Cafe?
We're so glad you asked! BOOST Cafe is the most comprehensive online community for out-of-school time. The Cafe is an extension of BOOST Collaborative and is 100% free for users. We aim to support the out-of-school time field by providing a hub full of relevant, up-to-date, easy-to-implement resources and tools.
Who do we serve?
Stay tuned to BOOST Cafe updates and more by receiving our newsletter.
Sign up here.
Here's how you can get started:
Discover thousands of free resources in our Resource Center as well as grants, scholarships, and more on our Funding Page.
Stay informed, connect, share, support, and learn on our interactive forum. Be a part of our online professional development community.
Browse through our Vendor Marketplace featuring a wide variety of innovative products and services to enhance your programs.
Access a variety of speakers, consultants, coaches, and trainers in our Speakers Corner dedicated to meeting your staff development needs.
Our #BOOSTchat page (more coming in Phase 2) will feature Twitter chats from thought leaders gathering to discuss important issues in OST.
Here's what's brewing in
of BOOST Cafe!
Online Film Festival
Downloadable E-Cards
Advertising Packages
Publications & Tools:
a full library white papers and field research


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Discover how Smile More Composite Veneers can help you
At Smile More Dental Care, we're committed to providing you with a composite veneer treatment that we believe suits you. Our composite veneer treatments have helped enhance and add confidence to our patients' smile.
The Process involves the following steps:
1) Planning
The new smile is first planned and designed according to the specific requirements of the patient. This occurs during the foundational examination stage.
2) Wax-up Model of New Smile
A model of the desired new smile is then created using the information collected in the assessment and planning stage.
The teeth are then prepared according to the planned smile design. The wax-up model can be used to create a Preparation Guide.
This is a silicone putty index that makes sure that the teeth are prepared exactly according to the design and so is a conservative preparation technique.
This way no more than necessary tooth is trimmed back. Find out more.
4) Creating a model on which to manufacture the veneers
Moulds or an impression using a silicone material in the mouth is taken of the prepared teeth.
This is then sent to the dental technician in a laboratory together with all other relevant records.
This is where the veneers will be handcrafted and manufactured.
5) Creating a Trial Smile
If the patient would prefer to have more control of the final result or the dentist needs to check the functioning of the planned teeth, then a Trial Smile becomes a necessary step.
A Trial Smile is constructed with the aid of the wax-up model and is made up of a incredbily durable plastic material and will look just like the final teeth in the mouth. It allows the patient to see if this is how they would like the final teeth to look.
It also allows the cosmetic dentist to check how these new teeth are working in the mouth. The Trial Smile is usually left on for a minimum of two weeks.
6) Manufacture of the veneers
During the two-week period, the ceramist at a dental laboratory will be handcrafting the new teeth according to the dentist's instructions and prescription.
Once the veneers have been created we then check the fit of each veneer on the corresponding teeth.
When we are happy with this we then move onto the next stage which is cementation.
7) Cementation of Veneers
This is a process where we physically and chemically bond each veneer to the corresponding tooth.
The process involves using various acidic and chemical resin agents that literally glue the porcelain to the teeth. Find out more.
8) Finishing and cleaning up
Each tooth is then cleaned of any residual cement.
After which each tooth is then polished using a special set of instruments that fix to the dentist's handpiece or "drill". There is no cutting involved here.
9) Series of Post-Operative Checks
The cosmetic dentist then goes through a series of checks with the patient to make sure that the final teeth operate and function as planned.
An important check here is to make sure that the patients chewing ability are not hindered. The dentist then also makes sure that the aesthetics are correct.
Oral hygiene and self-care of the mouth are also reviewed at this stage.
10) Review Appointment
This is when the patient is called back for another appointment for the dentist to carry out another series of checks to make sure that the teeth are functional and that the aesthetics are as the patient wished.
Smile More Dental Care is committed to providing you with a treatment we best believe suits you. By contacting us on 0207586120 or by booking an appointment today, we can begin your journey for an improved, confident smile.
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text: RichC 1 Posted January 1, 2018 Hello i would appreciate some advice. My partner and i moved to QLD in February from the UK and we have permanent residency status (we love it) Annoyingly we moved out shortly after Brexit when the Pound had massively dropped in value so only brought enough money over to get started and get on the property ladder. I do feel as though the Pound will regain some of its former strength eventually but i wouldnt be surprised if it takes another 3 years or so I have substantial savings just sat in a bank in the UK earning less than inflation and some stocks and shares held within ISA's which i can no longer contribute to and maximise as im no longer living in the UK, plus some rental properties. I have been waiting for a Bear market or at least a market correction (surely it must be coming soon !) to invest the money sat in the bank in three or four low cost unmanaged index trackers probably with Fidelity.co.uk (who i have my ISA's with) to capitalize on the cheap stock prices then hopefully enjoy the next rise in the markets by which time i am hoping the Pound will have gained some strength against the Dollar. At this point in the future i would hopefully be able to move some or all of the money over to OZ to use here or just invest in an Ozzy fund provider for future retirement. What im not sure on is the potential Tax implications on profits made on those shares and any issues regarding timing of moving money over to OZ. Im looking to make my savings and assets work for me but and be efficient as possible but dont want to fall foul to Tax Issues like being taxed in both countries or paying more Tax than necessary. I dont know if anyone has been in a similar situation but all advice is welcome. Thanks Richard Share this post Link to post Share on other sites


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Hopefully you'll only use this app for good and not evil.
"Lightweight Keyboard Spy. Some of the features: stealth mode, log encryption, capturing of clipboard changes and currently used process, log viewer. Public version has several limitations: program shows it-self when started; stealth mode is deactivated when hot key is pressed (without password prompt)."
What do abbreviations or keywords like <*5>,
These abbreviations are used to display all no-displayable characters and some additional information.
|<*3>, <*4>, <*5>, etc.
|Identify repetition of an immediately preceding character, example: w<*3> means "www".
|Common combinations of CTRL key and C, F, S, V, X, Z characters, accordingly.
|No printable keys: "backspace", "enter (new line)", "tab", "insert", "delete", "windows key", "home", "end", "pause" - accordingly.
|Arrows keys: left, right, up, down - accordingly.
|Function keys, from F1-F12.
|Currently focused process, identified by "Name" and "PID" of the process.
|Current content of the clipboard, identified as "Text".
NOTE: These mappings are valid for current version 2.55, and may be changed at any time.
Source :ooker - A free portable key logger app:


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There's a reason for the term "scaredy-cat." Cats are sensitive creatures, they are the pets we most tend to associate with timid curiousity or over-reaction. Here are some of the stranger things cat owners have reported their cats are fearful of, curated from responses on Reddit and YouTube.
Watch this cats reaction to a pretty flower…
"One of my cats is petrified of carrot peelings and the other one rolls around in them" – B1ngers
"My cat does not like it when I take a shower. I live alone so I don't bother leaving the bathroom door closed. He will sit in the bathroom and scream his head off once he hears the water running." – ZeD00m
"My cat flips at the sight of a plastic bag. I have no idea what it is, but if he sees one he runs for his life." – Gum_Bumper
"Steam. My genius dork of a cat is terrified of steam. If I have my cup anywhere near him, he'll bolt." – Klaudiapotter
"The hoover: the bringer of cleanliness and death" – surebegrandlike
"My cat is afraid of the ceiling fan NOT moving. If it is going, that's all good. If it is still, freaks him out and super paranoid!" – fdoerzy
Check out this video that went viral, watch closely for the true horror timed at 2.26 in.


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We have identified a region within the ectodomain of the fusogenic human immunodeficiency virus type 1 (HIV-1) gp41, different from the fusion peptide, that interacts strongly with membranes. This conserved sequence, which immediately precedes the transmembrane anchor, is not highly hydrophobic according to the Kyte-Doolittle hydropathy prediction algorithm, yet it shows a high tendency to partition into the membrane interface, as revealed by the Wimley-White interfacial hydrophobicity scale. We have investigated here the membrane effects induced by NH2-DKWASLWNWFNITNWLWYIK-CONH2(HIVc), the membrane interface-partitioning region at the C terminus of the gp41 ectodomain, in comparison to those caused by NH2-AVGIGALFLGFLGAAGSTMGARS-CONH2(HIVn), the fusion peptide at the N terminus of the subunit. Both HIVc and HIVn were seen to induce membrane fusion and permeabilization, although lower doses of HIVc were required for comparable effects to be detected. Experiments in which equimolar mixtures of HIVc and HIVn were used indicated that both peptides may act in a cooperative way. Peptide-membrane and peptide-peptide interactions underlying those effects were further confirmed by analyzing the changes in fluorescence of peptide Trp residues. Replacement of the first three Trp residues by Ala, known to render a defective gp41 phenotype unable to mediate both cell-cell fusion and virus entry, also abrogated the HIVc ability to induce membrane fusion or form complexes with HIVn but not its ability to associate with vesicles. Hydropathy analysis indicated that the presence of two membrane-partitioning stretches separated by a collapsible intervening sequence is a common structural motif among other viral envelope proteins. Moreover, sequences with membrane surface-residing residues preceding the transmembrane anchor appeared to be a common feature in viral fusion proteins of several virus families. According to our experimental results, such a feature might be related to their fusogenic function.
The human immunodeficiency virus type 1 (HIV-1) relies on the fusogenic activity of the gp120/41 glycoprotein at the virion surface to enter and infect the CD4+ host cells (7, 24). Activation of the HIV-1 envelope protein occurs after the binding of the surface gp120 subunit to CD4 and human chemokine receptors (4, 7, 8, 24). Subsequently, the transmembrane gp41 subunit supports structural rearrangements involving a coiled-coil domain (5, 12, 25,39) that bring about the eventual exposure to the aqueous medium of the fusion peptide at its N terminus (12, 13, 24, 25). The fusion peptide is likely to insert into the target lipid bilayer, making gp41 capable of interacting simultaneously with the viral and cell membranes (5, 8, 12, 13, 25, 39). The involvement of this conserved hydrophobic segment of about 25 amino acids in triggering fusion is supported by prediction (13, 15, 40), mutational analysis (2, 10, 11, 35), and in vitro studies carried out using synthetic peptides and model membranes (16, 20,23, 27-31, 36). Fusion peptides inserted into the target membrane might drive the aggregation of gp41 trimers at initial sites of fusion as well (39). It has been argued that a higher-order envelope glycoprotein complex is involved in HIV-1 fusion as well as in analogous viral fusion processes (17, 19, 39).
Recent resolution of the atomic structure of the gp41 ectodomain demonstrates that this region is organized into a very stable helical bundle or "hairpin" (4, 5, 39). The core of this crystallized structure is constituted by a triple-stranded coiled coil. Three α-helices oriented obliquely in an antiparallel sense pack hydrophobically against the core coiled coil. The resulting trimeric structure would locate both fusion peptides and transmembrane anchors at the same end of the molecule. Two main models have been developed to explain the involvement of the hairpin structure in the gp41-mediated membrane fusion process. In one model (4, 5, 12, 25, 39, 43) a transient intermediate exists between the native nonfusogenic and the fusogenic six-helix complex, termed by Chan and Kim (4) as the "prehairpin." The alternative model postulates that the hairpin is already present in the prefusion state (38). Binding to CD4 and chemokine receptors would expose the hairpin in close vicinity to the target membrane. Both molecular models propose that this structure represents the fusion-active version of gp41. Thus, formation of a hairpin could be coupled to the apposition of the target cell and viral membranes provided that gp41 trimers interacted simultaneously with both membranes.
The hypothesis of the hairpin structure as a fusion mediator has gained support from studies indicating that synthetic peptides corresponding to helical regions in the gp41 core structure are inhibitors of HIV-1 fusion. The DP-178 synthetic peptide representing the hydrophobic α-helix that interacts with the coiled-coil core of the hairpin completely inhibits virus-mediated cell-cell fusion and reduces infectivity (43). DP-178-induced inhibition occurs after receptor binding-induced activation and blocks the fusion process at a hemifusion state (12, 25). This peptide (also called T-20) has already been tested in clinical trials and has been shown to be an effective suppressor of HIV-1 replication in infected individuals (19a). In addition, based on the knowledge of this functional structure new strategies for the development and identification of new anti-HIV compounds have recently been delineated (8a, 9a).
At this point it is unclear how hairpin-apposed membranes can fuse (4). Several findings indicate that the fusion peptide inserted into the target membrane would cause the distortion of the bilayer organization necessary for merging (6, 30). Hydropathy-at-interface plots elaborated according to the hydrophobicity scale developed by Wimley and White (33, 42,45) identify, in addition to the fusion peptide, a second region within the ectodomain of the fusogenic HIV-1 gp41 that shows high tendency to partition into the membrane interface. This tryptophan-rich region is located proximal to the viral membrane overlapping the DP-178 region at its C terminus and preceding the transmembrane anchor of gp41. Recent mutational analysis has revealed its importance for gp41-mediated fusion and infectivity. Salzwedel et al. (34) identified several mutations indicating that this gp41 stretch is dispensable for the normal maturation, transport, and receptor-binding ability of the protein but required for membrane fusion. Later functional characterization in cell-cell fusion assays by Muñoz-Barroso et al. (26) revealed three different phenotypes among the studied gp41 mutants: wild-type-like phenotypes showing reduced activity, defective variants unable to mediate fusion, and mutants able to assemble nonexpanding fusion pores.
Our results here demonstrate that, as for the N-terminal fusion peptide, HIVc, a sequence representing the pretransmembrane region partitions into membranes and induces the same type of perturbations. Moreover, the fusion peptide stimulates the activity of this second membrane-interacting sequence. These observations would be consistent with the existence of concerted action by both sequences that could simultaneously destabilize gp41-apposed membranes at the points of fusion. A mutation shown to inhibit cell-cell fusion and virus entry without affecting the maturation, transport, or CD4-binding ability of HIV-1 glycoprotein (34) caused the abrogation of both membrane fusion by the membrane-bound peptide and the ability to form complexes with the N-terminal fusion peptide. This finding provides a direct correlation between the activity of the HIVc peptide in vitro and the activity of gp41 in the virus and the transfected-cell context. Hydropathy analysis of several X-ray-solved ectodomain structures further indicates that, following the intervening protein sequences involved in the hairpin formation and preceding the transmembrane anchor, an additional membrane-interacting domain is also present. Sequence analysis extended to other viral fusion proteins indicates that an unusual concentration of aromatic residues, just preceding the transmembrane anchor, is commonly found among several virus families including retroviruses, filoviruses, orthomyxoviruses, rhabdoviruses, alphaviruses, and flaviviruses.
We propose that the existence of a membrane interface-residing sequence close to the transmembrane domain can be a general motif for a considerable number of viral fusion proteins and may be related to their fusion activity. Our study of the gp41 pretransmembrane region provides a mechanistic basis for understanding its role in viral fusion and infection and might be important for devising new inhibitors based on this sequence.
Materials.Dioleoylphosphatidylcholine (DOPC), dioleoylphosphatidylethanolamine (DOPE), cholesterol (CHOL), and the fluorescent probesN-(7-nitro-benz-2-oxa-1,3-diazol-4-yl)phosphatidylethanolamine (N-NBD-PE) and N-(Lissamine-rhodamine B-sulfonyl)phosphatidylethanolamine (N-Rh-PE) were purchased from Avanti Polar Lipids (Birmingham, Ala.). 8-Aminonaphthalene-1,3,6-trisulfonic acid sodium salt (ANTS) andp-xylenebis(pyridinium)bromide (DPX) were from Molecular Probes (Junction City, Oreg.). Octaethyleneglycol monododecyl ether (C12E8) and Triton X-100 were obtained from Sigma (St. Louis, Mo.). All other reagents were of analytical grade. The sequences NH2-DKWASLWNWFNITNWLWYIK-CONH2(HIVc), DKAASLANAFNITNWLWYIK-CONH2[HIVW(1–3)A], and NH2-AVGIGALFLGFLGAAGSTMGARS-CONH2(HIVn) were synthesized as their C-terminal carboxamides and purified (estimated homogeneity, >90%) by Quality Controlled Biochemicals, Inc. (Hopkinton, Mass.). Peptide stock solutions were prepared in dimethyl sulfoxide (spectroscopy grade).
Vesicle preparation.Large unilamellar vesicles (LUV) consisting of DOPC, DOPE, and CHOL (molar ratio, 1:1:1) were prepared according to the extrusion method of Hope et al. (18) in 5 mM HEPES–100 mM NaCl (pH 7.4). Lipid concentrations of liposome suspensions were determined by phosphate analysis (3). The mean diameter of DOPC-DOPE-CHOL vesicles was 130 nm as estimated by quasielastic light scattering using a Malvern Zeta-Sizer instrument.
Fluorimetric assays for vesicle destabilization.All fluorescence measurements were conducted in thermostatically controlled cuvettes (37°C) using a Perkin-Elmer LS50-B spectrofluorimeter. The medium in the cuvettes was continuously stirred to allow the rapid mixing of peptide and vesicles.
Membrane lipid mixing was monitored using the resonance energy transfer (RET) assay described by Struck et al. (37). The assay is based on the dilution of N-NBD-PE and N-Rh-PE. Dilution due to membrane mixing results in an increase in N-NBD-PE fluorescence. Vesicles containing 0.6 mol% of each probe were mixed with unlabeled vesicles at a 1:4 ratio (final lipid concentration, 0.1 mM). The 7-nitro-benz-2-oxa-1,3-diazol-4-yl NBD emission at 530 nm was monitored, with the excitation wavelength set at 465 nm. A cutoff filter at 515 nm was used between the sample and the emission monochromator to avoid scattering interferences. The fluorescence scale was calibrated such that the zero level corresponded to the initial residual fluorescence of the labeled vesicles and the 100% value corresponded to complete mixing of all the lipids in the system. The latter value was set by the fluorescence intensity of vesicles labeled with 0.12 mol% of each fluorophore at the same total lipid concentration as in the fusion assay.
Release of vesicular contents to the medium was monitored by the ANTS-DPX assay. LUV containing 12.5 mM ANTS, 45 mM DPX, 20 mM NaCl, and 5 mM HEPES (9) were obtained by separating the unencapsulated material by gel filtration in a Sephadex G-75 column eluted with 5 mM HEPES–100 mM NaCl (pH 7.4). Osmolarities were adjusted to 200 mosM in a cryoscopic osmometer (Osmomat 030; Gonotec, Berlin, Germany). Fluorescence measurements were performed by setting the ANTS emission at 520 nm and the excitation at 355 nm. A cutoff filter (470 nm) was placed between the sample and the emission monochromator. The 0% leakage corresponded to the fluorescence of the vesicles at time zero; 100% leakage was the fluorescence value obtained after the addition of Triton X-100 (0.5% [vol/vol]).
Peptide-membrane and peptide-peptide interactions.Peptide-vesicle and peptide-peptide interactions were investigated by monitoring the change in emitted Trp fluorescence. In order to produce an intrinsically fluorescent sequence, Phe8 was replaced by Trp within the HIVn peptide. Control experiments demonstrated that the resulting fluorescent analog was equally active at inducing membrane destabilization (data not shown). The peptide-vesicle mixtures were incubated for 10 min at 37°C and then for 1 h at room temperature before data acquisition. Corrected spectra were recorded in a Perkin-Elmer MPF-66 spectrofluorimeter with excitation set at 280 nm and slits of 2.5 nm (excitation) and 10 nm (emission). The signal was further corrected for inner-filter effects.
Peptide partitioning into DOPC-DOPE-CHOL LUV was estimated by physically separating unbound and bound peptides. Unbound peptides were removed from the mixtures by gel filtration in a Sephadex G-75 column. Vesicles (1 ml; 1 mM total lipid) were incubated at 37°C for 15 min with peptides prior to gel filtration. Chromatographed peptide-lipid samples containing bound peptides were subsequently solubilized with 2 mM C12E8 in order to minimize the scattering contribution to Trp fluorescence. The Trp signal at 333 nm (excitation at 280 nm) was normalized to the amount of coeluted lipid that was simultaneously quantified also by means of spectrofluorimetry. To that end, we used liposomes labeled with 0.1 mol% of N-NBD-PE and N-Rh-PE. In addition to lipid quantification, NBD and rhodamine fluorescence measurements confirmed complete vesicle solubilization by C12E8. With [L] and [W] as the molar concentrations of peptides in lipid and water, respectively, the apparent mole fraction partition coefficient was estimated as described previously (41, 42) using the following expression: Kapp = {([PT − [PF])/[L]}/([PF]/[W]) where [PT ] is the molar concentration of peptide added to samples before chromatography and [PF] is the peptide concentration in aqueous solution after incubation with vesicles. The latter can be determined from where F0 and F represent Trp fluorescence emission intensities in the peptide-vesicle mixtures before and after chromatography, respectively.
A classical way of detecting amino acid stretches bearing hydrophobic character in proteins is to plot their so-called average hydropathies (21, 42). As shown in Fig.1, for gp41 ectodomains in primate lentiviruses, such a plot based on the widely used hydropathy scale of Kyte and Doolittle (21) clearly identified two conspicuous areas on the hydrophobic side above the zero midpoint line. The N-terminal hydrophobic regions consisted of the fusion peptides, whereas the regions at the C terminus represented the transmembrane anchors.
The hydropathy index for each amino acid adopted by Kyte and Doolittle (21) was an estimate based on bulk phase partitioning of side chain hydrophobicity alone. As recently proposed by White and Wimley (42), other contributions, specifically those arising from the peptide bonds and the bilayer effect, must be taken into account in order to compose a hydrophobicity scale that could be useful to detect membrane-interacting amino acid sequences. Thus, these authors elaborated a whole-residue scale based on the water-to-membrane interface transfer free energies for each amino acid (45). This "interface scale" was determined for 1-palmitoyl-2-oleoylphosphatidylcholine bilayer interfaces using two types of oligopeptides, which allowed the evaluation of both side chain and peptide bond hydrophobicities.
When average interfacial hydrophobicity was plotted for gp41 ectodomains of primate lentiviruses, two main hydrophobic regions were also detected (Fig. 1). The region at the N terminus was coincident with that detected by the Kyte-Doolittle hydropathy plot, meaning that the interfacial hydrophobicity plot identified the fusion peptide as well. However, at the C terminus a clear segregation between the hydrophobic region detected by the Kyte-Doolittle plot and that detected by Wimley-White interfacial hydrophobicity occurred. The latter was shifted closer to the N terminus. This finding is further illustrated by the data displayed in Table1. For the three analyzed lentiviruses, the positions of the hydropathy-positive peaks at the gp41 N terminus coincided in both types of plots, the only difference being that the hydrophobic regions detected by the Kyte-Doolittle plot were somewhat wider. In contrast, the positive maxima detected by Wimley-White within the ectodomain C-terminal region were shifted 15 to 20 residues toward the N terminus.
The position of the hydrophobic region at the C terminus in the Kyte-Doolittle plot (residues 681 to 707 in HIV-1) is almost coincident with that of the putative transmembrane segment of gp41 (residues 684 to 706 in HIV-1). We conclude that, at the C terminus of the gp41 ectodomain, there exists a wide nonpolar region (approximately 40 residues long) which is segmented into two domains: one located somewhat farther from the protein C terminus (residues 664 to 683 in HIV-1) showing high propensity to reside within the membrane interface and another one closer to the C terminus, which constitutes the membrane-spanning anchor. The hydrophobic-at-interface region (residues 664 to 683) detected within the C terminus of the gp41 ectodomain does not merely reflect the common preferential localization of aromatic residues within the interfacial boundary regions that precede transmembrane segments (22, 32). Both the peak range and the intensity of the hydrophobic maximum indicate that, for this fusogenic viral subunit, the stretch of membrane surface-residing amino acids that precedes the transmembrane domain is uniquely elongated (compare Tables 1 and 3 and see Discussion below).
Figure 1 identifies a second membrane-partitioning domain within the gp41 ectodomain (residues 664 to 683) in addition to the fusion peptide (residues 512 to 534). Since the whole-residue interfacial hydrophobicity scale was composed on the basis of the partitioning into zwitterionic membrane interfaces (42, 45), we characterized the membrane-interacting capabilities of that second C-terminal region by using a representative synthetic sequence, HIVc, and electrically neutral LUV as targets. Previous work by our group (28, 29) has shown that the partition of a sequence representing the fusion peptide at the N terminus of HIV-1 gp41 (HIVn) has the capacity to destabilize neutral liposomes composed of DOPC, DOPE, and CHOL (molar ratio, 1:1:1). These vesicles select for an extended peptide structure that becomes fusogenic in a dose-dependent fashion. Morphological data reveal the formation of nonlamellar lipidic aggregates during the time course of lipid mixing (30). At subfusogenic doses the fusion peptide also causes the release of trapped contents from liposomes, indicating the existence of a peptide-mediated permeabilization process prior to and independent from the development of fusion (28, 29). For comparative purposes we explored the ability of HIVc and HIVn to perturb DOPC-DOPE-CHOL membranes. Assuming that both sequences would be present at an equimolar ratio within a potential fusogenic complex during gp41-mediated fusion, we also analyzed the membrane-perturbing abilities of a HIVc-HIVn mixture (1:1 mole ratio).
The HIVc peptide induced membrane fusion in the DOPC-DOPE-CHOL LUV system employed in this study, as evidenced by the occurrence of membrane lipid mixing. Figure2A presents comparative results of membrane lipid mixing for the three peptide samples, HIVc, HIVn, and HIVc-HIVn, as monitored with the RET assay. The final extents of fusion were dependent on the peptide-to-lipid ratios in the three cases. However, data displayed in Fig. 2 readily demonstrate that, in terms of peptide added per lipid, the HIVc sequence was more efficient at inducing lipid mixing than HIVn. For HIVc we consistently found that the peptide-to-lipid ratio required to induce 20 to 30% lipid mixing was 1:1,000. In comparison, HIVn induced 10% lipid mixing at a 10-times-higher peptide-to-lipid ratio of 1:100. The mixture HIVc-HIVn did not achieve better results than HIVc by itself. These data strongly support the idea of HIVc being capable of destabilizing membranes and inducing them to merge. Moreover, they suggest that this sequence is a more potent perturbing agent than HIVn.
Analogous results were obtained when the three peptide preparations were assayed for their ability to release the ANTS-DPX probes from the aqueous interiors of the DOPC-DOPE-CHOL vesicles (Fig. 2B). Peptide-induced leakage was activated in all cases at peptide-to-lipid ratios lower than those that activated lipid mixing. In addition, HIVc was again more potent than HIVn at lower peptide-to-lipid ratios. At a peptide-to-lipid ratio of 1:5,000 the extent of leakage induced by HIVc consistently amounted to more than 30%, whereas, to obtain a comparable extent of fusion, the ratio had to be increased 10-fold. HIVn induced 10% leakage at a peptide-to-lipid ratio of 1:1,000, whereas a ratio of 1:100 was necessary to detect a comparable amount of lipid mixing. The mixture HIVc-HIVn paralleled the behavior of HIVc alone.
Taken together, results in Fig. 2 would be consistent with the existence of membrane perturbations caused by HIVcpartitioning into DOPC-DOPE-CHOL vesicles that are qualitatively similar to those caused by HIVn partitioning. However, compared to HIVn, 10-times-less HIVc was necessary to promote comparable lipid mixing or leakage. This fact may reflect an inherently higher potency to perturb membranes for the HIVc sequence or else more peptide associated with vesicles in HIVc-treated samples. To clarify this issue, the peptide binding to vesicles was investigated next.
In Fig. 3 we show the fluorescence spectra obtained utilizing HIVc and the fluorescent F8W analog of HIVn. At a peptide-to-lipid ratio of 1:100 levels of intrinsic fluorescence emission in HIVc and in HIVn changed significantly in the presence of DOPC-DOPE-CHOL LUV. Emission intensity was enhanced, and the maxima shifted to lower wavelengths: from 346 to 342 nm for HIVcand from 354 to 347 nm for HIVn. Both effects suggest that Trp residues in the presence of vesicles sense a less polar environment which is indicative of partition and the subsequent penetration of both peptides into the bilayer millieu. We observed that the levels of Trp fluorescence of both peptides in solution decreased with time, an effect that may be related to self-aggregation due to their hydrophobic character. This process may compete with membrane association and, therefore, precludes correct determination of real partition coefficients (41). With this caveat in mind, and just for comparative purposes, we determined apparent mole fraction partition coefficients (K app) for HIVc and HIVn (F8W analog). For a peptide-to-lipid ratio of 1:500, we obtained under our experimental conditions (see Materials and Methods) 93% of HIVc coeluting with vesicles whereas that value was reduced to 35% for HIVn. Therefore theK app values were 7.3 × 105 for HIVc and 3.0 × 104 for HIVn. Again, these values should not be taken as quantitatively reflecting the energetics of the peptide-membrane interaction process, but rather as descriptive of the ability of these peptides to associate with membranes under our particular experimental conditions. They further indicate that, after correcting for the difference in bound peptide, membrane-associated HIVn is as effective as HIVc at perturbing membranes (Fig. 2). Thus, in our in vitro assays, the activity displayed by HIVn is actually limited by the ability of the peptide to partition into vesicles, but this activity in the membrane-bound form would be comparable to that of HIVc.
The extents of fusion and leakage seem to indicate that the mixture HIVc-HIVn followed a membrane-perturbing pattern similar to that exhibited by HIVc alone. However those measurements were carried out after 1 h of incubation of peptides and vesicles. It is possible that the initial rates of membrane perturbation might be altered by the combination of both peptides. Thus, in search for a possible synergism in the mode of action of HIVc and HIVn, we carried out a kinetic characterization of the initial stages of the perturbing processes induced by each of the peptides and by the HIVc-HIVn mixture. Initial rates of HIVc-induced lipid mixing increased with peptide concentration (Fig. 4). We investigated the effect of coadding HIVn on the former process under conditions where this peptide alone did not induce lipid mixing or induced it just marginally (i.e., at peptide-to-lipid ratios ranging from 1:1,000 to 1:100). As shown in Fig. 4, the initial rates of lipid mixing induced by the mixture HIVc-HIVn were always higher than those induced by HIVc alone. At a ratio at which HIVn induced extensive lipid mixing by itself, i.e., 1:25, no additive effects of the HIVc-HIVn mixture were found. This indicates that, under most circumstances, synergism between these peptides in the mode of inducing fusion may occur. Similar results were obtained for the leakage assay, and again potentiation of peptide effects was more evident at lower peptide-to-lipid ratios (Fig.5).
The existence of HIVc-HIVn interactions underlying their mutual synergism was confirmed by detecting changes of HIVc Trp fluorescence in the presence of the nonfluorescent HIVn. The data displayed in Fig.6 reflect an increase in the emitted fluorescence intensity of HIVc in solution and a shift of the wavelength of maximum emission (λmax) from 346 to 340 nm when HIVc was premixed with HIVn at a 1:10 HIVc-to-HIVn mole ratio. Results in this figure further indicate that the Trp emission of HIVc premixed with HIVn (curve 4) also increased and was slightly blue shifted from 342 to 338 nm when associated with vesicles. This effect was clearly larger than the one detected for the fluorescent HIVc alone (curve 3). According to the estimated partition coefficients, under the experimental conditions in Fig. 6, ≈60% of HIVc was bound to vesicles. Thus, the polarity change caused by premixing with HIVn might be due to an increase in binding or might originate from a different bilayer localization of HIVc when interacting together with HIVn and/or from the formation of HIVc-HIVn complexes within the vesicle membranes.
In order to confirm the relevance of the previous observations, we also explored the effect of a sequence substitution on the ability of HIVc to perturb membranes and associate with HIVn (Fig. 7). The HIVW(1–3)A sequence with the first three Trp residues of HIVc replaced by Ala represents the pretransmembrane region of a mutant gp41 described by Salzwedel et al. (34) as reproducing the phenotype of deleting the sequence spanning residues 665 to 682. This phenotype consists of the specific abolition of cell-cell fusion and virus entry mediated by gp41 without affecting normal maturation and transport to the cell surface or CD4-binding ability of the envelope glycoprotein. Our results in Fig. 7A show that, in contrast to HIVc, the HIVW(1–3)A peptide was unable to induce membrane fusion at peptide-to-lipid molar ratios ranging from 1:1,000 to 1:100. Since the absence of an effect might be caused by the existence of defective binding, we also measured the partitioning of this sequence into vesicles. At a 1 mM lipid concentration approximately 50% of the added HIVW(1–3)Apeptide partitioned into DOPC-DOPE-CHOL membranes yielding aK app of ≈55,000. This means that for the fusion experiments in Fig. 7A the 1:100 HIVW(1–3)A/lipid ratio condition is comparable to that of the 1:500 HIVc/lipid ratio. We conclude that HIVW(1–3)Abound to membranes was unable to induce the type of perturbations induced by the HIVc parental sequence.
The ability of HIVW(1–3)A to associate with membranes may also be inferred from the emission spectra displayed in Fig. 7B. As for HIVc and HIVn (Fig. 3) the intrinsic fluorescence of HIVW(1–3)A increased in the presence of vesicles, indicating that Trp residues must be sensing a less polar environment. In contrast to the observed effects for HIVc(Fig. 6), under comparable conditions the emission of HIVW(1–3)A did not experience any change in the presence of the nonfluorescent HIVn (data not shown). The latter result seems to reflect the absence of HIVW(1–3)A-HIVn interactions.
The existence of a membrane interface-residing sequence preceding the transmembrane anchor might represent a particular characteristic of primate lentiviruses or else a structural motif shared by other retroviruses and other families. To explore this hypothesis, we first performed on several viral sequences a hydropathy analysis analogous to those described in Table 1 for primate lentiviruses. The selected fusogenic sequences (or close homologous relatives) have been either predicted or formally demonstrated to form hairpin structures. Data in Table 2 indicate that, with the single exception of Sendai virus F protein, there exists within the analyzed sequences a hydrophobic-at-interface region preceding the transmembrane segment. Paramyxovirus-mediated membrane fusion does not require the sequences connecting the coiled coil and the transmembrane anchor and might take place according to a mechanism distinct from that proposed for the rest of the virus families analyzed (1) (see Discussion). As a control, a similar hydropathy analysis of transmembrane regions of several human type I membrane proteins (Table3) revealed that segregation of the hydrophobic-at-interface domain from the transmembrane segment is not found in those proteins. The preferential occurrence of aromatic residues at the cytoplasmic boundary of transmembrane segments in the human proteins (22, 32) does not account for the position and length of the interfacially hydrophobic sequences detected in viral envelope proteins.
Elongation of sequences containing aromatic residues at the N termini of membrane-spanning regions is common in viral envelope proteins implicated in viral fusion. Figure 8shows sequences from six virus families aligned with respect to the membrane-spanning hydrophobic region rich in aliphatic amino acids. TheRetroviridae have been further subdivided into their principal subfamilies, Lentivirinae, types B, C, and D, avian Oncovirinae, and Spumaretrovirinae. A high degree of clustering of aromatic amino acids, most prominently tryptophan, is found in the primate and ovine lentiviruses, mammalian oncoviruses of groups B, C, and D, the filoviruses Ebola virus and Marburg virus, the rhabdovirus vesicular stomatitis virus G protein, and the alphavirus Sindbis virus E1 protein. A lower level of clustered aromatics, but higher than expected for type I glycoproteins, is found in avian retroviruses, spumaretroviruses, influenza A virus HA2, and the hepatitis C flavivirus E2 protein. Such an unusual concentration of aromatic amino acids exists against a background of considerable sequence diversity and in different positions in the linear sequence, even among closely related viruses. There are notable exceptions to the pattern, however. As noted in Table 2, the frequency of preinsertion aromatic amino acids in Sendai paramyxovirus F glycoprotein does not exceed that expected for type I glycoproteins. Likewise, Arenavirus GP2 (not shown) lacks any clustering of aromatics. Therefore, while aromatic and especially tryptophan-rich regions prior to membrane insertion have membrane-distorting properties that could be involved in fusion by many viruses, such regions would not appear to be indispensable.
Viral fusion proteins are designed to interact simultaneously with two membranes during the fusion reaction cycle. Interaction with the virion membrane is primarily mediated by the transmembrane anchor. In addition protruding ectodomains contain a conserved hydrophobic stretch of amino acids, the fusion peptide, which is thought to insert into the target membrane upon fusion activation (4, 13, 14, 17, 19, 33,40). By using a hydropathy analysis based on the hydrophobicity-at-interface scale recently proposed by Wimley and White (45), we have confirmed the high propensity of the gp41 fusion peptide to partition into membranes (Fig. 1). According to our results (Table 1), within the HIV-1 fusion peptide region, the sequence IGALFLGFLGAAG containing the conserved FLG motif (13), shows a high probability to localize at the bilayer interface. Despite the experimental limitations inherent to the hydrophobicity-at-interface scale (45), the Wimley-White hydropathy analysis appears to be clearly superior to others for detecting potential membrane-interacting sequences within overall soluble polypeptide domains (42). The most important advantage in comparison with bulk phase scales is that the Wimley-White scale takes into account the effect of the membrane interface on partitioning. This bilayer region consists of a complex mixture of water and chemically heterogeneous phospholipid groups (polar head groups, glyceryl, phosphoryl, carbonyl, and methylenes) in which significant changes in polarity occur at short range (42). This results in the main difference between the Wimley-White scale and scales such as the one proposed by Kyte and Doolittle (21): even in the absence of solid physical foundations (46), aromatic residues, namely, Phe, Tyr, and Trp, appear to be the most hydrophobic ones when located at interfaces.
An illustrative example of the differences between scales can be observed for the C-terminal region within the gp41 ectodomain (Fig. 1). The Wimley-White hydrophobicity-at-interface scale identifies the region preceding the gp41 transmembrane anchor as having a high tendency to partition into the membrane interface. Its pronounced hydrophobic-at-interface character is based on the presence of 1 Phe residue, 1 Tyr residue, and 5 Trp residues closely located within a 20-residue spanning sequence. The preference of Trp and Tyr residues for boundary regions that flank the transmembrane domains is a known feature shared by virtually all known membrane proteins (22,32). The C-terminal region detected within the gp41 ectodomain appears to be an elongation tail of membrane surface-residing domains. To test the functional significance that such a membrane interface-residing domain could have for gp41-mediated HIV-1 fusion, we characterized it as a membrane-interacting sequence. During the course of our studies, Salzwedel et al. (34) reported on the effect of mutations targeted to the same tryptophan-rich domain. More recently, Muñoz-Barroso et al. (25) have evaluated the effect of those mutations on the various stages of fusion. The mutational and functional analyses have confirmed its crucial role during gp41-mediated fusion.
Proposed molecular models for viral fusion processes highlight a role for coiled-coil structures, which were first observed for influenza virus HA2 (44) and which have been extended to the retroviruses (15) and filoviruses (14). Formation of those stable structures could be energetically coupled to membrane apposition (4, 39). It is generally accepted that both anchoring and apposition of the viral and target membranes are mediated by the ectodomains at the transmembrane subunits of envelope proteins such as the HIV-1 gp41. Following gp41-induced apposition, a membrane perturbation is likely to take place within the points of fusion, causing both membranes to merge (4, 39). Within this framework, the fusion peptide is postulated to anchor the fusion protein to the target membrane and perturb subsequently apposed membranes. Our data indicate that the HIV-1 fusion peptide would be capable of both functions, given its tendency to partition into membrane interfaces and to perturb their architecture (29,30). In addition, our experimental data demonstrate that the sequence preceding the gp41 transmembrane anchor could be implicated in perturbing the apposed membranes as well. According to the leakage, lipid mixing, and binding assays, this sequence was even more potent at inducing membrane destabilization than the fusion peptide. The physiological relevance of our in vitro approach was supported by the fact that a mutation known to block gp41 activity in vivo completely impaired the ability of HIVc to perturb membranes (Fig. 7). Similarly, the in vitro membrane activity of the synthetic N-terminal fusion peptide has been also reported to be sensitive to sequence substitutions affecting gp41-mediated cell-cell fusion and viral infectivity (20, 29). Within the hairpin structure postulated to represent the fusion-competent version of gp41, both sequences would be closely located at the same end of the molecule. Moreover, if a higher-order envelope glycoprotein complex is involved in HIV-1 fusion, membrane perturbations induced by both sequences might be confined to the point of fusion (25, 26).
The presence of two membrane-partitioning sequences separated by a collapsible intervening sequence is a common motif shared by other viral envelope products. Results summarized in Table 2 demonstrate that, with the single exception of those of paramyxoviruses, known hairpin structures would locate two membrane interface-partitioning sequences in close proximity. Baker et al. (1) demonstrated that paramyxovirus-mediated membrane fusion does not require the flexible sequence connecting the coiled coil and the transmembrane anchor. These authors suggested that conformational changes in paramyxovirus F proteins may involve flexibility in other regions of the protein such as the intervening sequences connecting the N- and C-terminal heptad repeats. Thus, in contrast to what is found for the rest of the analyzed cases, flexibility between membrane-anchoring regions of the F protein would not suffice to allow hairpin formation.
Influenza virus hemagglutinin also appears to be unique in the sense that although hydrophobic-at-interface and hydrophobic peaks are located at different positions, both regions span almost the same sequence of approximately 25 to 27 residues, i.e., they are not segregated. Clearly, in order to find a common mechanistic role for these membrane interface-seeking regions during fusion, more mutational and functional studies will be necessary. We believe that the new Wimley-White hydropathy scale will be a powerful predictive tool that will lead to the detection of functional domains implicated in protein-membrane interactions during viral fusion events.
The existence of the hydrophobic-at-interface region preceding the transmembrane anchor appears to be a specific attribute of certain viral fusion glycoproteins rather than a general feature of type I membrane proteins (Table 3). In viral proteins, such a region appears to be an elongation of the short sequences containing aromatic residues at the cytoplasmic boundary of transmembrane anchors (22,32). A survey of such regions in a number of virus families indicates that they are common and especially prominent in the retrovirus and filovirus families (Fig. 8). While it is difficult to accurately align highly divergent sequences, the aromatic amino acids do not occur with any reproducible periodicity, as one would expect in the α-helical configuration suggested by Salzwedel et al. (34), even in closely related viruses. Any mechanism by which these regions participate in fusion must account for the positional variability.
An alternative explanation for the clustering of tryptophans in retroviruses relates to the genetic code, in that only the triplet UGG codes for tryptophan. Any G-to-A hypermutation by reverse transcriptase at any of five clustered UGG codons could generate a nonsense codon and premature stop in translation just prior to membrane insertion. This could generate a population of truncated glycoproteins accumulating during chronic infections, along with other defective mutants, as soluble glycoproteins that might function as cellular and immunological decoys, as does sGP in filoviruses. However, this explanation would not apply to those viruses such as murine leukemia virus preferentially rich in phenylalanine. The more likely general explanation for such preinsertion aromatic clusters is that they promote fusion through their membrane-distorting properties.
Taken together, these observations point to the possibility that a number of viral fusogenic subunits might operate by putting into close contact within the fusion locus two perturbed membranes, that of the virus and that of the target cell, and/or two interacting perturbing sequences, the fusion peptide and the surface-residing tail that precedes the transmembrane anchor.
We are grateful to Maier Lorizate for technical assistance.
T.S. and A.A. are recipients of predoctoral fellowships from the Basque Government. This work was supported by DGCYT (grant PB96-0171), the Basque Government (PI 96-46; EX-1998-28; PI-1998-32), and the University of the Basque Country (UPV 042.310-EA085/97; UPV 042.310-G03/98). Support to W.R.G. includes senior fellowship 1F32AI08549 and grant 1R01DE10862 from the National Institutes of Health of the United States.
- Received 27 March 2000.
- Accepted 30 May 2000.
↵* Corresponding author. Mailing address: Unidad de Biofı́sica (CSIC-UPV/EHU) y Departamento de Bioquı́mica, Universidad del Paı́s Vasco, Aptdo. 644, 48080 Bilbao, Spain. Phone: 34 94 6012615. Fax: 34 94 4648500. E-mail:GBPNIESJ{at}lg.ehu.es.
- Copyright © 2000 American Society for Microbiology


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Napa Novembers – So Much to be Thankful for
Nov. 9, 2010 | by Jim Beazley
They say you can see a New England Fall from outer space. But if you come to the Napa Valley in November you won't have to go that far. And with temperatures in the upper 60s it's downright balmy by comparison.
Early rains in October and the first Sunday of November have greened up our hills, turning California gold into Irish green. But the real show is in Napa's vineyards.Whether they're on hillsides or the valley's floor the vineyards are a rich tapestry of yellows, oranges and reds.
Used to be we'd say they "cut the phone lines and blocked the roads" when November came…that's how abrupt the High tourist season would end. With Napa's rebirth as the valley's food and Wine capital, things are changing.
On the Napa River, "Iron Chef" Masaharu Morimoto continues to wow his many followers at his new, high-end Morimoto Napa with his East-Meets-West combinations and imaginative sushi. Steven Barber, of Napa's Barbers-Q, has opened his new restaurant Fish Story to rave reviews. And Tyler Florence, a TV celebrity who has penned five cookbooks, is planning a rotisserie restaurant to fill out the new 3rd Street Waterfront complex on the new Napa Riverwalk.
Local's favorite Winter dishes and comfort foods–fresh vegetable soups, steaming mussels and simmering stews–are migrating back onto the menus at long established Napa eateries. Chef Marcos' award-winning chili is back at Celadon. Served with freshly baked cornbread made with jalapeno and sweet corn and a mixed green salad, it is only available at lunch. At night Celadon's signature mussels are sure to warm more than just your heart.
The word's gotten out how beautiful the Napa Valley is in November. It's like high season but without the crowds, and with the color turned up to maximum instead!


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Transition Words and Phrases
Transitional Words and Phrases
Transitional words and phrases are used to guide the reader through the text.
You've probably seen a lot of these common transitional words and phrases before but you may not have thought about what their operation is — what their purpose is in the paper. So let's look at different ways the transitions can be used. You can have transitions that show time information. For instance, after, before, during and in the middle of. These all tell you when in time something is happening. You can also have transitions that indicate an example that is about to be given — for example, in fact, for instance. If you say something, if you state your main idea and then you want to give a supporting example, you can say "in fact let me tell you this thing."
For example, dogs make good pets because they are very loyal. These phrases let you know that an example is coming. Transitions can be used for comparing — also, likewise — you're saying how two things are alike. This is also like this. Likewise, we can look at how dogs are good companions. You can also use them for contrasting, saying how two things are different — however, but, yet. You would like a dog for a pet because they are so companionable, but a cat is not going to be as affectionate. They won't make as good of a companion as the dog. So you can contrast two things using however, but, yet. Transitions can be used to suggest additions to let you know that more is coming. And, also, furthermore. These all let you know more is coming. More examples are coming, more information is coming. More details of the same sort. You can have transitions that reflect logical relationships — if, then, therefore, as a result, since. If I go to bed late, I might be tired in the morning. I went to bed late, therefore, I was tired in the morning. So these transitions reflect logical relationships. And our last example for transitional words and phrases are steps in a process. These words show that exactly. They're showing the steps in a process. First, you'll gather up all your ingredients. Second, you'll mix the dry ingredients in a bowl. Last, you'll take the cake out of the oven. So these steps are telling you exactly what's happening. 1st, 2nd, 3rd. They may thrown in next, after that, they may not want to just put numbered all the time — like last isn't telling you the tenth step, it just uses the transitional word last but it still is giving you of what step that is in the process. So, make sure you use your transitional words and phrases where they will orient your reader and illuminate the structure of your composition. You want to let your readers know where they are in your paper.
If you're saying first this happens, next, this happens or for steps in a process – first you do this, second you do this. Or if you are comparing or contrasting things you would say well, here's this, likewise, there's this – however, there's this if you are contrasting. And you want to illuminate the structure of your composition. You're writing a contrast and comparison essay, these comparing and contrast transitional words are going to help highlight that that's what type of essay you're writing. If you're writing a persuasive essay, you might see a lot of examples. If you're writing an instructional essay, you might see a lot of steps in a process. If you're writing an informational essay, you may have some logical relationships.
So using these transitional words and phrases you can help your reader know what the purpose of your writing was. So, please always use transitional words and phrases in your writing cause you want to guide your reader through the text and let them know what your purpose is.


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Analyst - Business Intelligence - French Speaking
- Salary:
- £31500 to £35000 per annum + benefits + OTE + bonus
- Location:
- Deadline:
- 3rd February 2020
- Start date:
- Job type:
- Graduate job
- Sectors:
The Company
Are you a fresh graduate looking for a new and exciting opportunity in a multinational company? Do you like the idea of working with world leading investment firms, consultancies and corporations? Then look no further…
I am working with a leading company within their industry who are looking for analysts to join their team of 300 people in central London. With over 1,000 employees globally and offices in 7 countries around the world including New York, Hong Kong and Los Angeles, they continue to double their turnover every two years since they started in 2007: their success speaks for itself!
In short, they are one of the industry's largest and most established expert network who serve hundreds of global business's and specialist industry experts worldwide. They help clients make better informed business decisions by giving them compliant and confidential access to top industry experts through one-to-one consultations, reports, meetings and roundtable events. Sounds up your street already?
The Role
They are looking for self-motivated, driven and passionate graduates to join their team of Analysts. They pride themselves on having an open and collaborative work environment and value creativity of thought - there's no limits to your ability to grow and be part of their success story!
Analysts are the engine of the business. They work as the intermediary between clients and industry experts to increase the value of their clients business decisions. It's a fantastic opportunity to develop strong interpersonal skills, broaden your commercial skillset and progress quickly in a goal orientated team.
The work is fast paced - you will be working on multiple projects at once, spanning a wide variety of industries and geographies. You often will be having conversations with clients about sector developments which you could be reading about days or months later in the pages of the Financial Times.
- Bachelor Degree
- Eligibility to live and work in the UK
- A client service-focused mind set
- Ability to communicate effectively and build relationships quickly over the phone and face-to-face
- A resourceful nature, with a diligent and proactive approach to work
- The ability to work well within a team, under pressure and with a positive attitude
- Fluency in French
They offer a competitive salary of £31,500-£35,000 plus bonus, along with accelerated career progression for successful and ambitious individuals. There is a dynamic and sociable working culture including monthly socials, company trips and Friday drinks.
Sounds like the perfect role? Get in touch and we can arrange a call!
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Kevin Hart: Ripped to Shreds for Posting About Jussie Smollettby Hilton Hater at .
Just like many celebrities before him, Kevin Hart posted a lengthy message on social media yesterday in response to Jussie Smollett getting brutally beaten for being gay.
Unlike many celebrities before him, however, Hart has a history of homophobic Tweets and quips.
And the Internet was not about to let the so-called comedian forget it.
Smollett, one of the key cast members on the FOX drama Empire, was harassed and then assaulted by two men in Chicago very early on Tuesday morning.
They hurled anti-gay and racist slurs at the actor, only to then wrap a rope around his neck and pour bleach all over him, after fracturing his ribs and injuring Smollett in other ways as well.
It was a truly horrific attack.
Shortly after news of this heinous incident went viral, Hart Tweeted the following:
"Sending prayers your way @jussiesmollett ….This is unbelievably sad.
Why are we going backwards….this is disgusting. We as people have to do better. WTF is going on the world???? Why are we falling in love with hate????
God damn it people….Choose love…I repeat…Choose love.
I will forever choose love and I will continue to teach my kids how to do the same. Stand strong brother.
Nice sentiment, we suppose, but here's the thing:
Hart recently lost the job of Academy Awards host after the public learned that he had posted many anti-gay messages back in the day, while also making awful jokes on stage about homosexuality.
"One of my biggest fears is my son growing up and being gay," Hart once said, adding: "If I can prevent my son from being gay, I will."
Har har? Not exactly.
This viewpoint wasn't lost on Internet users, either.
"This is why someone's jokes about beating their gay son were never funny," wrote TV writer Ira Madison III, while filmmaker Sam Greisman, who is the son of actress Sally Field, agreed.
"But keep joking about beating up your kid for being gay, Kevin Hart!" he wrote directly to/about Hart.
Elsewhere, along these similar lines:
Poet Saeed Jones referenced Hart's post-Oscars scandal interview with Ellen DeGeneres, who urged people to give the comedian a second change, writing:
"Given what we've seen so far, I fully expect the men who attacked Jussie Smollett to score a sit-down interview with Ellen at some point in the next few weeks.
"Maybe it will be a roundtable discussion with Kevin Hart."
The two men who beat Smollett up screamed "This is MAGA country" at the star, according to various reports.
President Trump has not yet commented on the assault or this aspect of it, either.
The Chicago Police Department says detectives are investigating the incident and "treating it as a possible hate crime," while the FBI is looking into a death threat that had previously been sent to Smollett.
Click down below for the latest developments -- and join us in sending Smollett your very best wishes.


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The New $pace Race and Closing Gitmo
The race to Mars and the new technologies that will get us there; inside Guantanamo Bay and what really happens behind the camp's walls.
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