text:
NEWS8 May 2012
NEWS8 May 2012
US— ComScore has applied its hybrid web measurement approach, Unified Digital Measurement (UDM), to version 2.0 of its Mobile Metrix service.
UDM uses a mix of user-based and site-based measurement. In the case of Mobile Metrix, ComScore has a panel of 10,000 smartphone users who have downloaded a piece of tracking software to their devices. Meanwhile, tags on websites and those within apps provide a census-level view on media usage.
The company described the development – a year in the making – as "an important milestone on the path to delivering, in a single interface, comprehensive reporting of digital audiences across technology channels".
MKM Partners expands and rebrands https://t.co/9hvYd66Cy9 #mrx #marketresearch
BPC details how pollsters have changed methodology https://t.co/s5mLYR7nYn #mrx #marketresearch
Marketers under pressure to measure external factors since Brexit https://t.co/jmaxmTUFGQ #mrx #marketresearch


text:
Udder Nonsense
"My wife and I took our 2 girls to the University of MO's College of Vet Medicine's open house in 2002. We took lots of pictures and this gem was discovered by my mom when we were showing her the pictures a few weeks later. Even with sophomoric minds, my wife and I hadn't noticed the great placement of the cow's udder in relation to me standing there."
(submitted by Scott)
Even More Behind The Awkwardness
The Incredible Hulk
"My cousins got together for a Christmas family photo. Everyone was asked to wear...
Friendly Conversation
Even More Behind The Awkwardness
Santa's Little Helpers
"This is a picture of my family taken in 1981. If you could sum up my family with...
Latest Awkward
Bachelor Baby Shower
"My cousin sent these thank-you cards for her baby shower. I decided to do a...
Refrigerator Editorial
"I sent this picture to most of my family. I just noticed what my dad did to the...
Married…With Zombies
Every couple has its own unique obstacles to overcome on the way to being happy...

subset: commoncrawl


text:
Thursday, August 25, 2011
Yo . this is a t shirt design . its for the south african locals . visagie in south africa is like the equivalent of murphy in the overseas. larnies are the rich okes from the overseas. thanks
Up for voting now at
Subscribe to: Post Comments (Atom)


text:
- Home
- Bike Checks
- Photos
- Videos
- Product
- News
- Forum
- Store
Vital MTB
sspomer's videos 0 of 1912 « Previous Next »
ONE LAP - Enduro World Series, Argentina, Stage 3 - Josh Lewis & Iago Garay
Kamloops Kickout World Champs & UrbaNduro Ultimate Fight Club with Santa Cruz
Aaron Chase & Tomas Lemoine Hit the Trails in Laguna - SIXSIXONE
Short but Sweet - 2016 Giant Factory Off-Road Team Intro Video
Stevie Smith, Connor Fearon and Mark Wallace Hauling in New Fox Racing Gear
Bar Drag Bounty is Back - Win a Rocky Mountain Maiden Park DH Bike
Just posted my entry, hoping the RAW style will go down well here...
Am I alone in thinking its not that attractive of a bike? Also that the chainstays are too short?
You're alone. Very, very alone.
Is that a rux?
don't care what y'all say I'm uploading tons of uphill bike pushing footy
so 15 second instagram video only??? boo
No problemo- I only need two seconds
Hello Vital MTB Visitor,
We're conducting a survey and would appreciate your input. Your answers will help Vital and the MTB industry better understand what riders like you want. Survey results will be used to recognize top brands. Make your voice heard!
Five lucky people will be selected at random to win a Vital MTB t-shirt.
Thanks in advance,
The Vital MTB Crew


text:
Bannerconnect is an independent specialist facilitating automated trading on both national and international levels.
Platform for the buying and selling of quality digital media. Previously known as Ad Safe.
Integral Ad Science is leading in Top 10K Sites, Top 100K Sites, Top 1M Sites and The Entire Web.
In terms of market share, Banner Connect is clearly lagging behind, losing to Integral Ad Science in all segments.
Integral Ad Science has better usage coverage in more websites categories. Including News & Media, Arts & Entertainment, People & Society, Business & Industry and 122 other categories.
Banner Connect is leading in Pets, Holidays and Financial Management.
Integral Ad Science is leading in most countries, including United States, United Kingdom, Canada, France and 66 other countries.
Banner Connect is leading in Albania, United Arab Emirates and Ghana.


text: Home > Lifestyle > Woman > News 25 August 2009 Testosterone impacts women's careers Higher testosterone levels may make some women more likely to choose high-risk financial careers, a US study suggests. 0 Quiz Is my diet healthy? » 10 odours our noses can identify 6 body language mistakes to avoid Higher testosterone levels may make some women more likely to choose high-risk financial careers, a US study suggests. "In general, women are more risk-averse than men when it comes to making important financial decisions, which in turn can affect their career choices," Paola Sapienza, an associate professor at the Kellogg School of Management at North-western University, said. "For example, in our sample set, 36% of female MBA students chose high-risk financial careers such as investment banking or trading, compared to 57% of male students. We wanted to explore whether these gender differences are related to testosterone, which men have, on average, in higher concentrations than women." For this study, Sapienza and colleagues measured testosterone levels in saliva samples collected from about 500 MBA students at the University of Chicago Booth School of Business. The students also took part in an experiment to determine the link between testosterone levels and risk aversion. What the researchers found Higher levels of testosterone were associated with a greater taste for risk in women, but not in men. But in women and men with similar levels of testosterone, there was no gender difference in risk aversion. The researchers also found that the link between risk aversion and testosterone predicted post-graduation career choices. Those with high levels of testosterone and low risk aversion were more likely to go into high-risk financial careers. "This is the first study showing that gender differences in financial risk aversion have a biological basis, and that differences in testosterone levels between individuals can affect important aspects of economic behaviour and career decisions," study co-author Dario Maestripieri, a professor in comparative human development at the University of Chicago, said. "That the effects of testosterone on risk aversion are strongest for individuals with low or intermediate levels of this hormone is similar to what has been shown for the effects of testosterone on spatial cognition." The study appears in the Proceedings of the National Academy of Sciences. - (HealthDay News, August 2009) NEXT ON HEALTH24X Experience a contact lens that feels like nothing 2016-10-24 12:49 More: WomanNews advertisement Read Health24's Comments Policy Comment on this story 0 comments Comments have been closed for this article. Logout Comment 0 characters remaining Share on Facebook Loading comments... Other news Medical 'I believe it's easier to live with HIV than being diabetic' Medical 2 HPV shots can prevent genital warts News 5 stories to show how different young and old people are Diet and nutrition What to eat during Ramadan? Here's a complete meal plan Medical Lack of sleep doubles chances of dying from heart disease Lifestyle Laser skin therapy – could this be the answer to your skin problems? From our sponsors WIN a R2000 Skin Renewal voucher! Constipation in women SA's old diesel vehicles continue to fuel allergies Live healthier Dangerous winter sun » Why female students ignore the risks of indoor tanning Can rooibos protect you from the effects of UVB exposure? Skin cancer always a risk – even in winter During winter, the risk of skin cancer doesn't disappear. CyberDoc talks to us about when to see your doctor about a strange-looking mole or spot. Did you know? » The 5 saltiest foods may surprise you Craving salt? Your genes may be the reason 10 fascinating facts about salt The one thing that fast foods, whether it be chips, hamburgers, pretzels or fried chicken have in common, is loads of salt.


text:
Paper Supplies
- Health and Beauty products
- Digestive Aids
- Organic CL 1285 Original Probiotic Fermented Rice
- Last products viewed
Organic CL 1285 Original Probiotic Fermented Rice Product ID: NFR0410563 Bio-K Plus International
- "We appreciate the quick delivery!
- "Thank you for the quick shipment of my order. I had searched locally for the product I bought from you, but was unable to find it. I was very happy to have found it on your website. I have never ordered from you in the past, so was unsure what to expect. The product was exactly as described and shipped very quickly. Thank you very much....and I'll shop with you again.
Organic CL 1285 Original Probiotic Fermented Rice
Product Id: NFR0410563
Sold as: Case of 6Weight: 1.56 lbs
List Price: $37.40Savings: $8.95
DescriptionShips Refrigerated Extra shipping appliesBio-K Plus InternationalMfg#: 00026
Bio K Plus Organic CL 1285 Original Probiotic Fermented Rice, 3.5 Fluid Ounce -- 6 per case.
95 Percentage Organic, Gluten Free, Wheat Free, Dairy Free
ingredients: Sprouted brown rice milk solids, organic agave syrup active, organic brown rice protein, nutritional yeast, natural vanilla extract, organic locust bean gum, bacterial cultures of L. acidophilus CL 1285® and L. casei Lbc80r, pectin.
Hot products
Reynolds Plain Interfolded Aluminum Foil Sheets product id: UFR711 Aluminum Foil
Soodhalter Plastic Par T Forks product id: PI73180004 Drinking Straws and Coffee Stirrers
Our commitment to you
We are so glad you stopped by FoodServiceDirect.com. We stock over eighty thousand foodservice products including Organic CL 1285 Vanilla Probiotic Fermented Rice. If you need any info about Organic CL 1285 Vanilla Probiotic Fermented Rice or any of our other items call us at 757-245-7675 We have been a leader in the foodservice industry for almost 20 years. We have worked hard to attain our A rating from the Better Business Bureau and we will do our utmost to satisfy you with Digestive Aids!


text:
Explore Memes and more!
Some people are just so Does the term not mean anything to you? Anything at all?! This is why you'll never be anything more than an assistant
Shake Shake,Mischief Managed,Memes
This is why I struggle with writing anything that will be "public" like on a forum or group.
Mischievous Hump day – When regular humor does not cover it | PMSLweb More
Laila Ali Lifestyle
Or I will pull the INTP Chameleon card and slip right in like I've known them for years.<<<Haha yep. It depends in the place and people. I only just got comfortable enough to pull a chameleon:)
ways to tell a woman is mad at you
The Characters,Star Wars,Personality Types,Weird,Twitter,Memes,You Must,Rain,Watches


text:
Explore these ideas and much more!
Awesome How to Make a Spectacular Floor Lamp with Logs #DIY #Handmade #LED…
How to keep the glitter from falling off your Christmas decorations.
Wood Sign Ideas More
Get some clear glass cups from Target or any store of your choosing and Use Qtips to dip in paint to decorate your glass anyway you want.
Awesome for bottles into cups or could use the same principle for taking off the bottom of wine bottles! I want to do this with everything!
I need to make this! !!
Painted with chalkboard paint to the glass, you can use chalk to write on the ~ ~ >>> more interesting content, please follow @ wonderful cr ...
e07a1fcf756db2d00be86c5000d77745.jpg 640×1,403 pixels
Bre! This is what Patrick needs for his baseball team. He just needs to change the team names. lol


text:
The 2017 Formula One Monaco Grand Prix. Join the conversation here.
If you have any questions, please don't hesitate to ask. There's no such thing as a stupid question.
Old Racing Club threads
Discussion in 'GTR 2' started by Stefan Beemsterboer, Nov 26, 2009.
Page 1 of 116
Page 1 of 116


text:
Similar companies
Songea Urban Water Supply and Sanitation Authority (SOUWASA) is an Autonomous Government Agency ope...
The first permanent residents of Zanzibar seem to have been the ancestors of the Hadimu and Tumbatu,...
WHEREAS all the Political Parties which are represented in the Parliament of the United Republic of...
Makambako is a medium-sized town and ward in the Njombe Region of the Tanzanian Southern Highlands,...
Handeni ni mji katika Mkoa wa Tanga katika kaskazini-mashariki ya Tanzania na moja kati ya wilaya 10...
7532 views
Posted: 13 Apr 2016 09:02
Category: Government & Development
Location: Africa , Uganda
Address: Unnamed Road, Uganda
Email: firstname.lastname@example.com
Web Site: http://www.budget.go.ug
Contact Name: BUYENDE LOCAL GOVERNMENT.
Phone: n/a
Buyende is a town in the Eastern Region of Uganda. It is the main municipal, administrative, and commercial center of Buyende District.
Location on the map:
Coopera teWith Us »
We are looking for partners all over the world to work with eastafricatender.com Interested persons and companies please contact us on email - john.paul@aesl .co.tz Details >>


text:
Written on: 09/07/2013 by glannaghfamily (1 review written)
Great spacious apartment for family with 4 kids. Convenient for tubes and local shops. Apartment was spacious, clean and airy. The check-in was arranged to suit us coming off the flights so that we could leave our luggage off. Thanks for that. Will definitely recommend housetrip.com.
As rated by our community of reviewers
" Fast, easy and cheap " Read More
" Wonderful Sicily trip " Read More
Written by Brisandy
" Fantastic " Read More
" Great customer service " Read More
" Good service " Read More


text:
Personal Statement
To provide my patients with the highest quality healthcare, I'm dedicated to the newest advancements and keep up-to-date with the latest health care technologies....more
To provide my patients with the highest quality healthcare, I'm dedicated to the newest advancements and keep up-to-date with the latest health care technologies.
More about Dr. Ashwani Singh
Dr. Ashwani Singh is a renowned General Physician in Shahdara, Delhi. You can meet Dr. Ashwani Singh personally at Gopal Nursing Home & Eye Hospital in Shahdara, Delhi. Save your time and book an appointment online with Dr. Ashwani Singh on Lybrate.com.
Lybrate.com has an excellent community of General Physicians in India. You will find General Physicians with more than 35 years of experience on Lybrate.com. You can find General Physicians online in Delhi and from across India. View the profile of medical specialists and their reviews from other patients to make an informed decision.
Lybrate.com has an excellent community of General Physicians in India. You will find General Physicians with more than 35 years of experience on Lybrate.com. You can find General Physicians online in Delhi and from across India. View the profile of medical specialists and their reviews from other patients to make an informed decision.
Book Clinic Appointment
Gopal Nursing Home & Eye Hospital# B1, West Jyoti Nagar, Shahdara,Landmark: Near Durgapui Chowk, Delhi, Delhi Get Directions
View All
Consult Online
Text Consult
Send multiple messages/attachments
7 days validity
Diagnostic Cardiac Procedures
Get Cost Estimate
Treatment of Endoscopic Sinus Surgery
Get Cost Estimate
Treatment of Lumbar Radiculopathy
Get Cost Estimate
Oxygen Therapy Treatment
Get Cost Estimate
Hiv Prophylaxis Post Exposure
Get Cost Estimate
Restylane Vital Procedure
Get Cost Estimate
Treatment of Shin Splints
Get Cost Estimate
Treatment of Shin Splits
Get Cost Estimate
Management of Smoking Cessation
Get Cost Estimate
Treatment of Tetracycline Stains
Get Cost Estimate
Weight Management Treatment
Get Cost Estimate
Allergy Treatment
Get Cost Estimate
Allopathic Treatment
Get Cost Estimate
Asthma Management Program
Get Cost Estimate
Dengue Treatment
Get Cost Estimate
Skin Detoxification Treatment
Get Cost Estimate
Gastrointestinal Disorders
Get Cost Estimate
Head And Neck Pain Treatment
Get Cost Estimate
Health Check Up
Get Cost Estimate
Health Screening For Men
Get Cost Estimate
View All Services
Submit Feedback
Submit a review for Dr. Ashwani SinghYour feedback matters!
Nothing posted by this doctor yet. Here are some posts by similar doctors.
40 years old male from Bhubaneswar asked
Are there any long-term effects associated with taking ADHD (attention deficit hyperactivity disorder) medications? If so, what are they and what medications are implicated? What exactly is a spine block injection? Will it work long-term for low back pain due to disc problems? What causes Hashimoto's thyroiditis, and what is the best method of treatment? Can iodine help this condition?
General Physician, Mumbai
Use of stimulant decreases the symptoms to a much good effect and if we don't give stimulant medication there will be more of conduct disorder and progress in disease and for side effects we have to monitor the person and advice them accordingly and spine block injection is effective for six months.
27 years old male from Delhi asked
Maine kuch tym pehle gym may steroids ka use kiya, of phr daily masturbation, ab mujhe sex may problm aane lag gyi. Or kamori lagne lag gyi. Please koi sahi treatment suggest kro.
BAMS, MD Ayurveda
Sexologist, Lonavala
32 years old male from Mumbai asked
Hii I am hcv+ and going to marry soon my would be wife well aware of it please suggest me wut all precautions planning needs to be taken to prevents and avoid transmission to my partner as well as our would be baby.
DNB (Obstetrics and Gynecology), PGDHHM, MBBS
Gynaecologist, Delhi
there is little chance of transmission to the partner if you are in monogamous relationship. avoid sharing shavers toothbrush etc,and also get your virus load checked you may require medicine to decrease load
20 years old male asked
I have bad habit of masturbation since last 4 years. Please suggest me, what should I do to get rid off these habit?
• Do exercise daily in the evening, this will make you tired at night. And since masturbation is often done at night, so when you are exhausted, you will give preference to sleep not to masturbation. • Avoid sitting on your bed. Use a table/chair, and always sit with other people. • When the urge is very intense take a cold shower! It is not only shown to calm the mind but have many other benefits to overall health and energy. • Think about your family or anyone else and if they were watching you. • When you feel the need to masturbate, take a brisk walk or jog. Always try to occupy yourself when the urge arises. • Exercise more and get out of the house. This is a great way to take your mind off everything. • Motivate yourself by reminding yourself that abstaining will increase sexual performance, because if you don't do it as much you will have more energy and be more easily aroused when you have sex with someone, whoever it may be, and also you will have a stronger orgasm since you are less desensitized to the feeling. For optimum hormone levels, keep masturbation to no more than once a week. Studies in men have shown that not masturbating for up to a week slightly increases testosterone, after this it goes back down. • Take your mind off it with (non-sexual) music. • Set tiny goals for yourself, start with going 3 days clean, the third day is the speed bump, get past that and you KNOW that you're committed. Then go a week, then 10 days, then two weeks, then 17 days, etc. • Try fasting. Abstain from food or drink in a few hours everyday can distract your mind from sexual urge. Fasting will also act as a diet from stimulating food or drink for a certain period. If you do it regularly you will have better control upon your urge.
24 years old male from Chandigarh asked
The patient complains feeling like vomiting and loose motions. The patient is alcoholic and is a smoker also. His weight has also reduced as he was not having much food from 1,2 months he preferred fruits only. After going for various tests in the hospital all reports are normal. The liver reports are near the normal levels. But under chest x-ray PA veiw there is some kind of infection or damage found in chest. And after sputum test TB is also found. The potassium and sodium ratings are : potassium On 16/6/2016 - 2.5 On 18/6/2016 - 1.9 Sodium On 16/6/2016 - 130.6 On 18/6/2016 - 128 The blood pressure of patient is low from last 4,5 days near by 100-70. The hospital has discharged the patient saying he is normal now. His TB medicine started but he after taking medicine he feels like vomiting, loose motions starts and he also had 2 vomits after 1st dose which came out with some orange substance with some liquid. He is also getting fever everyday around 100-101°. Can anyone please guide me what should be done now, why he feels like vomiting & loose motions and what diet can be given to him as he is not in a condition to take heavy diets as nOw also he feels like Vomits and loose motions sometimes. Please guide and help me out regarding this.
Diploma in Tuberculosis and Chest Diseases (DTCD), MBBS
Pulmonologist, Delhi
Anti TB medicine taken empty stomach can cause vomiting, even pot klor should not be taken empty stomach. Continue repeating LFT every week bc anti TB drugs can cause liver damage which can lead to vomiting.
16 years old male from Hyderabad asked
Am 27 year old male, can any one suggest me best medicine for corn on fingers on hand? Been suffering from 5-6 months.
Homeopath, Delhi
Hi. Apart from using corn caps, you can also use antim crud 30 thrice a day for 15 days. Also apply thuja ointment on it, twice daily. If problem still continues, consult a homoeopath personally.
18 years old male from Warangal asked
General Physician, Nashik
Make a schedule. Children need to eat every three to four hours: three meals, two snacks, and lots of fluids. If you plan for these, your child's diet will be much more balanced and he'll be less cranky, because he won't be famished. I put a cooler in the car when I'm out with my kids and keep it stocked with carrots, pretzels, yogurt, and water so we don't have to rely on fast food. Plan dinners. If thinking about a weekly menu is too daunting, start with two or three days at a time. A good dinner doesn't have to be fancy, but it should be balanced: whole-grain bread, rice, or pasta; a fruit or a vegetable; and a protein source like lean meat, cheese, or beans. I often make simple entree soups or Mexican chili ahead of time and then freeze it; at dinnertime, I heat it up and add whole-grain bread and a bowl of cut-up apples or melon to round out the meal. Don't become a short-order cook. A few years ago, I got into a bad habit. I'd make two suppers -- one that I knew the kids would like and one for my husband and me. It was exhausting. Now I prepare one meal for everybody and serve it family-style so the kids can pick and choose what they want. Children often mimic their parents' behavior, so one of these days, they'll eat most of the food I serve them. Bite your tongue. As hard as this may be, try not to comment on what or how much your kids are eating. Be as neutral as possible. Remember, you've done your job as a parent by serving balanced meals; your kids are responsible for eating them. If you play food enforcer -- saying things like "Eat your vegetables" -- your child will only resist. Introduce new foods slowly. Children are new-food-phobic by nature. I tell my kids that their taste buds sometimes have to get used to a flavor before they'll like the taste. A little hero worship can work wonders too. Marty refused to even try peas until I told him that Michael Jordan eats his to stay big and strong. Now Marty eats peas all the time. Dip it. If your kids won't eat vegetables, experiment with dips. Kathleen tried her first vegetable when I served her a thinly cut carrot with some ranch salad dressing. My children also like hummus, salsa, and yogurt-based dressing.
29 years old male from Gurgaon asked
I am facing issues with stomach digestion issues. If my all reports are okay, could you please tell me how I can cure it. In last part if my report, I have some issues. Please advice treatment.
Bachelor of Unani Medicine and Surgery (B.U.M.S)
Ayurveda, Kanpur
65 years old male from Jabalpur asked
I am 63 years old and have been taking medicines for hypertension for last 14 years. I am 160 cm tall and weighing 68 kegs. I am not diabetic. I got worried only when my tmt test came+tive and Dr. advices me for angiography. I want to know whether there is any other noninvasive method to ensure about coronary blockage? If angiography is a must to do where should I get it done from? Presently I am not feeling any discomfort or chest pain neither at rest nor during exercise. I am taking telmisartan 12.5 with chlortalidone 12.5 and supermet AM tabs regularly. I live at Jabalpur MP. Kindly advice. Thanks.
General Physician,
Your b p. Is under control by medication good thing you don't have diabetes. Your weight slightly on overwt by7 to 8kg try to reduce it. Go for regular morning walk followed by free hand exercises. And balanced and diet. Do not change or regulate the medication without consulting your physicians. To know if there is any blockage of coronary arteries. You should go coronary angiography. It is safe it can be done in any good hospital where catch lab facility's are available.
25 years old female from Hyderabad asked
I am taking homeopathy medicines for my dust allergy problem. But I don't feel its working on me. Sneezing and nose part was very sensitive. Even a small hair strand also irritating if it falls on nose. And blackness around the mouth too. Can you suggest best medicines.
Homoeopathic medicine ALLER AID tab ( BAKSON) chew 1 tab twicedaily POTHOS Q + ECHENESIA AUG Q +TEUCRIUM Q .All 3 medicines of SBL company.30 ML each.Mix all 3 medicine in an empty 100 ml bottle.Now start taking 15 drops from this bottle in 20 ml fresh water 3 time daily. During Emergency attacks of sneezing POLLINOSAN Drops or BOOUME 27 ( BIOFORCE) Drink 5 dropss direct on tongue every 2-3 minutes till sneezing subsides. Precautions 1.Dont go near any ort of plant or grass. 2.Avoid dust a much as you can.While driving two wheeler place a wet hanky on nose to save yourself from dust.. 3.Avoid strong smell like smell of petrol,paint and perfumes. 4.Avoid Raw onions in salad. 5Avoid cold drinkss,Fat food,Fried food,Chilled drinks,Ketchups,Pakoras,dry fruits. 6.Eat healthy home made food consiting of green vegetable and pulses. 7.Daily Early morning ALOM VILOM PRANAYAM for 15 minutes.is a musst.
Shared 1 month ago • Featured Tip
B.H.Sc (Food Science & Nutrition), M.H.Sc (Food Science & Nutrition)
Dietitian/Nutritionist, Mumbai
Onions and sunstroke
Have you heard of farmers keeping an onion with them while working in blazing hot sun and also eating lot of onions do you know the reason behind this?
Onions due to its high sulphur content prevents body fevers that can be caused due to sun stroke. Farmers in gujarat and rajasthan keep an onion below their cap to keep the heat from getting to them.
Eat atleast 2-3 onions a day especially if you are out in sun to prevent sunstroke.
34 years old male from Udaipur asked
I am urinating very frequently. Almoat once in a hour or 2. What shall I do. I do drink decent amount of water.
General Physician, Delhi
20 years old male from Kolkata asked
Homeopath, Surat
A bent penis is an erect penis that curves to one side or the other and in most cases, it is absolutely normal. A curved penis simply can be a result of individual anatomy. If, however, your penis has a pronounced curve or bends sharply especially if penetration is impossible or if an erection is painful you should see a urologist. You may suffer from Peyronie's disease where scar tissue develops in the penis. The direction that an erect penis takes depends on the proportion of crus (penis under the skin) to exposed penis. Men with a shorter crus, and thus a longer penis, are more likely to have an erection that points downward, while an erect penis that has a longer crus will probably point outward, or even straight up. Sometimes the penis also bends to the left or to the right. In the vast majority of cases, the curve falls well within the norms of most men and should not be a deterrent for a relationship. If you feel that your penis has an abnormal shape is to go to a urologist to make certain that this curvature doesnot indicate some problem. Once in a while, a man does have a more pronounced curve than most. Even the majority of these men donâ?t have a problem in bed, although a few may have to adjust the positions they use. In some cases, however, a man may have Peyronie's disease, a condition that can make sex impossible. Peyronie's disease inflicts some men with a penis that bends so severely when it becomes erect that intercourse becomes impossible. The cause of Peyronieâ?s disease is unknown; in many instances, it arises as a result of an injury. The best advice for a man who has Peyronie's disease is to visit a urologist who can help you. Some men are so embarrassed by their condition that they refuse to get help, but urologists have helped many men with this problem, so you have no reason to be shy.
50 years old male from Vijayawada asked
Hai sir, Good Evening, I Subrahmanyam having sugar from last 2 years onwards my age is 51 having sugar before fasting 160 after fasting 210 can you please suggest me tablets.
MBBS, CCEBDM, Diploma in Diabetology
Endocrinologist, Hubli-Dharwad
Mr. lybrate-user, Thanks for your query. I have seen the details, which show you have a very high fasting glucose. And even PP is also high. There is no mention of HbA1c%, which would have given a better idea of how is the long term control. To suggest treatment I will have to know current treatment, dietary pattern and extent of daily exercise. Plus in this communication we are supposed to give only general guidelines, no prescriptions. So if you are really keen on better treatment then please come in a private conversation with all the details that I have mentioned above, then I will be able to give specific guidelines including prescriptions and diet advice. Thanks.
16 years old male from Bareilly asked
Bachelor of Ayurveda, Medicine and Surgery (BAMS), MD - Alternate Medicine
Ayurveda, Karnal
43 years old male from Bangalore asked
I am getting pain in the chest very often after eating, feels like pain in the esophagus tract, after eating during lunch or dinner. Due to my very busy schedule always, I forget to show it to the doctor or do not get time to visit doctor. Is it because of my routine, excessive driving to.
General Physician, Mumbai
Dear lybrateuser, - Your problem could be due to GERD -avoid spicy, fried, junk food, restrict tea, coffee to 1-2 cups per day, alcohol, tobacco if you take, sour foods, chocolate mint - chew your food well, do not skip meals, have meals on time, have 5-6 small meals including snacks rather than having three large meals, do not lye down for 1-2 hrs after meals, have dinner 2-3 hrs before bedtime, raise the pillow end by 5-6 inches when sleeping at night - take tablet Pan 40, 1 tab half an hour before breakfast daily - do regular exercise like walking whenever you get time, also do yoga & deep breathing for proper digestion.
40 years old male from Delhi asked
I am 39 years old male. I am a frequent traveller so eating outside happens very often. I love eating non-vegetarian food. I am very constantly have stomach problems which includes frequent motion some times, constipation other times, after every motion feels like bowel is clear but after half an hour or so comes up the feeling of going to motion again. Acidity has also been bothering me. What to do?
General Physician, Hyderabad
You need to control your diet . Eat less spicy food and try to control fat intake too . Eat small Neal every 2-3hours . Include fruits and raw vegetables in your diet . Include curd in your diet . Cut den on tea /coffee too . Exercise every day for at least 1 hour Take isabogol / husk in the night Take probiotics for good GI tract health Take care
Shared 1 year ago • Featured Tip
General Physician,
All about tea
When we speak of tea, it is commonly assumed to be black tea with milk and sugar. However, the word ?Tea? means any herb. This means even hot Tulsi water is Tulsi tea or hot mint water is Mint tea. Many herbs can be converted into tea such as jasmine tea, lemon tea, lemon grass tea, masala tea, sounf tea etc.
When the leaves are boiled in water and reduced to 50%, it is called Kadha (decoction). Black tea without milk and sugar is much healthier than black tea with milk and sugar.
Classical tea without sugar and milk has an astringent taste. But according to Ayurveda, this is good for health as it reduces Kapha imbalance. When sugar and milk are added, both of which have sweet taste, they neutralize the weight-reducing and kapha?relieving properties of the black tea. Therefore, milk or sugar should not be added to tea. For the purpose of taste, one can add Gur or jaggery or artificial plant sweetener Stevia.
Black tea is also a mild diuretic and increases urination as it contains caffeine, which is also a stimulant. This is the reason why tea is used when there is a need to stay awake. In this regard, coffee is stronger than tea. When taken in moderation, black tea is good for the heart and general health. If one has to choose tea then jasmine, lemon and lemongrass teas are better.
In Ayurveda, different teas have been prescribed for different personalities. Therefore, you can get vata?pacifying tea, pitta?pacifying tea and kapha?pacifying tea.
When we speak of tea, it is commonly assumed to be black tea with milk and sugar. However, the word ?Tea? means any herb. This means even hot Tulsi water is Tulsi tea or hot mint water is Mint tea. Many herbs can be converted into tea such as jasmine tea, lemon tea, lemon grass tea, masala tea, sounf tea etc.
When the leaves are boiled in water and reduced to 50%, it is called Kadha (decoction). Black tea without milk and sugar is much healthier than black tea with milk and sugar.
Classical tea without sugar and milk has an astringent taste. But according to Ayurveda, this is good for health as it reduces Kapha imbalance. When sugar and milk are added, both of which have sweet taste, they neutralize the weight-reducing and kapha?relieving properties of the black tea. Therefore, milk or sugar should not be added to tea. For the purpose of taste, one can add Gur or jaggery or artificial plant sweetener Stevia.
Black tea is also a mild diuretic and increases urination as it contains caffeine, which is also a stimulant. This is the reason why tea is used when there is a need to stay awake. In this regard, coffee is stronger than tea. When taken in moderation, black tea is good for the heart and general health. If one has to choose tea then jasmine, lemon and lemongrass teas are better.
In Ayurveda, different teas have been prescribed for different personalities. Therefore, you can get vata?pacifying tea, pitta?pacifying tea and kapha?pacifying tea.
0 year old male from Kasaragod asked
When we eat chicken what type of decision we will come what the effect of chicken. When eat chicken.
M.Sc - Dietitics / Nutrition
Organic and free range mean nothing, nutritionally. Red meat isn't bad for you. Pork is not too fatty. (much of it these days isn't nearly fatty enough!) yes, some fish has small amounts of mercury, but there are safe amounts. To the main question the answer is yes. You can eat too much of anything. There is no substance for which there is not a safe dose, and no substance for which there is not a toxic dose. All you need is a varied diet. Having said that, and not knowing how much chicken you eat at each meal, it doesn't seem likely that you're having a dangerous amount of it. But relax, enjoy your food, eat a varied diet, and don't stress about it.
36 years old male from Thane asked
From last few years i am frustrated due to Itching on my private parts. I.E. Mostly on my testicle area. I had a consultation with at least 5 Doctors till now but couldn't find out final solution for this. I am still not able to figure out what is it exactly. I never had any sexual relationship with anyone. I am not having any bad habits and i am maintaining a complete cleanliness with my whole body including my Private parts. I have applied different creams suggested by my MBBS Doctors e.G. Candidarma B etc. But not getting relief from this. Somtimes It is quite embarrassing during my working hours and in public places that i can't even touch my that area and also can't bare it. On this Portal i have already posted my query last week but got unprofessional and casual Answer from one Doctor that "Keep your Private parts clean. I don't remember who was that. Ok whatever or whoever he was, requesting others please help me to come out off this Problem and Make my life easy.
MD - Dermatology, MBBS
Dermatologist, Mumbai
Hello. It is difficult to diagnose without assessing the affected area. From your history, two probable reasons are either fungal infection or neurodermatitis. The diagnosis can be confirmed by a dermatologist after examination. Anti fungal creams like nizral cream twice a day would help in case it is fungal infection.
View All Feed


text:
Restaurants in Dundrum
Your restaurant search was for restaurants in Dundrum. On MenuPages.ie you will find a great choice of restaurants in Ireland to dine in. You can filter your restaurant search to show highest rated restaurants in Dundrum or show restaurants by cuisine like Fine Dining in Dundrum, Italian Restaurants in Dundrum, Asian Restaurants in Dundrum, Indian Restaurants in Dundrum or Bistro Restaurants in Dundrum.
Roly Saul The Restaurant
132 Reviews
Book Now
Roly Saul is situated in Dundrum, and is one of Dublin's fine dining restaurants where the staff and chefs pride themselves on delivering…
Deal of the day
Savour €60 Worth of Food for €30 for Two People in the critically-acclaimed Gusto, Parkgate St! Available to use until end of August
Your Indian Flavours
9a Main Street, Dundrum
Indian After a tenure, expanding over a decade in the restaurant sector, we realised that the…
5 reviews
Cafe Zest
Level 3, House of Fraser, Dundrum Town Centre, Dundrum
Breakfast, Cafe, Coeliac options,… Café Zest is located on level 3 of House of Fraser, Dundrum. A relaxed family friendly…
1 reviews


text:
|Home | About | Journals | Submit | Contact Us | Français
Based on the finding that tissue factor belongs to a group of genes upregulated in endothelial cells by VEGF, but not by EGF, we investigated signals selectively triggered by VEGF. Whereas the transcription factor early growth response (EGR)-1,which has previously been shown by us to be essentially involved in tissue factor gene regulation, was similarly induced by both factors, one major difference between VEGF and EGF signaling was the activation of the Ca++-mediated calcineurin/nuclear factor of activated T cells (NFAT) pathway by VEGF. Consistent with the importance of this pathway for tissue factor induction, treatment of endothelial cells with the Ca++ chelator BAPTA-AM, as well as the calcineurin inhibitor cyclosporin A, partially inhibited VEGF-induced tissue factor upregulation. Furthermore, tissue factor reporter gene assays revealed a synergistic cooperation of NFAT and EGR-1 in the induction of the TF promoter, and a physical interaction between the two factors was indicated by co-immunoprecipitation assays. Another gene upregulated by VEGF predominantly via NFAT, which is not induced by EGF, is the DSCR-1 gene. The calcineurin inhibitor DSCR-1 seems to be induced by VEGF in a negative feed-back loop to limit NFAT activation. When we tested adenoviral overexpression of DSCR-1, VEGF-mediated induction of tissue factor mRNA was reduced, and complete suppression could be achieved by a combination of viruses expressing DSCR-1 and NAB2, a corepressor of EGR-1. These findings support that both, NFAT and EGR-1, are required for tissue factor upregulation in response to VEGF.
Among the endothelial-specific receptors the vascular endothelial growth factor (VEGF) receptor family, in particular VEGFR-2 or Flk-1, is the major initiator of physiological and pathological angiogenesis (1). Additional endothelial cell-specific tyrosine kinase receptors of the Tie and ephrin receptor families control later stages of angiogenesis and vessel stabilization (2, 3). Aside from these receptors, which are almost exclusively expressed on endothelial cells, additional growth factor receptors such as EGF and TGF-β receptors are found in endothelial cells (3, 4). These are generally expressed on many different cell types and are presumably involved in the regulation of survival, growth and differentiation in concert with the cell type specific receptors.
We have previously found that the tissue factor (TF) gene is among the genes strongly upregulated by VEGF and have investigated its regulation by VEGF (5-7). TF is a distant member of the cytokine receptor family and functions as a high-affinity receptor for factor VII/VIIa initiating the blood coagulation cascade (8, 9). Aside from its important role in hemostasis (10-12), TF has been proposed to play a role in vessel formation. It is found to be expressed on tumor endothelium (13) and TF knockout mice die at gestation day 9.5 due to hemostatic problems indicating a possible failure in vasculogenesis (14). Additional data provide support for a signaling role of TF in the initiation of physiologic as well as pathologic angiogenesis through indirect factor VII-mediated activation of the PAR-2 receptor and direct TF cytoplasmic tail signaling (15-17).
The pathways leading to transcriptional upregulation of TF by inflammatory cytokines have been intensively investigated by us and others and are mainly dependent on activation of the nuclear factor kappa B (NF-κB) (10, 18, 19). Consistently, the NF-κB responsive element within the TF promoter is essential for inflammatory upregulation and overexpression of the natural inhibitor of NF-κB (IκB) and almost completely abrogates inflammatory TF upregulation (20). In contrast, TF upregulation during VEGF stimulation of endothelial cells does not appear to involve NF-κB. It is dependent in part on the transcription factor early growth response-1 (EGR-1), which is rapidly induced in response to VEGF treatment. The respective EGR-1 binding sites in the TF promoter have been previously shown by us to be essential for VEGF-mediated TF reporter gene transcription (6, 7).
Another strongly VEGF-upregulated gene which has turned out to be important for the control of gene expression has been recently identified by differential gene expression profiling (21, 22; B. Schweighofer and E. Hofer, unpublished data). This gene known as DSCR-1, calcipressin or MCIP1, was originally defined as one of the genes in the Down Syndrome Critical Region on human chromosome 21 (23, 24), and the protein encoded by this gene was found to bind to and inhibit the enzymatic activity of the serine/threonine phosphatase calcineurin (25). It was reported that VEGF can trigger DSCR-1 gene upregulation via multiple NEAT binding sites in its promoter (26).
As part of an effort to define characteristic signaling patterns induced by VEGF via VEGFR-2/Flk-l important for gene regulation and distinct from other tyrosine kinase receptors, we have compared the capacity of VEGF and EGF to induce signaling pathways and genes in endothelial cells. We show that in contrast to VEGF, EGF is not capable of inducing signals in endothelial cells sufficient for upregulation of TF. We define the Ca++-dependent activation of the transcription factor nuclear factor of activated T cells (NEAT) as a pathway important for TF induction, which is activated selectively by VEGF but not by EGF. We further provide evidence that NEAT functionally and physically cooperates with EGR-1 in TF gene regulation. In addition, we show that the DSCR-1 gene, which similar to TF is selectively upregulated by VEGF, acts as a negative regulatory factor together with the EGR-specific corepressor NAB2 (5) in limiting VEGF-mediated TF gene regulation.
Human umbilical vein endothelial cells (HUVEC) were cultured at 37°C and 5% CO2 in medium 199 (Invitrogen, Carlsbad, CA, USA) supplemented with 20% SCS (HyClone, Logan, UT, USA), 1 U/ml heparin, 50 μg/ml ECGS (Technoclone, Vienna, Austria), 2 mM glutamine, 100 U/ml penicillin and 1 mg/ml streptomycin (7). Cells were used for experiments up to passage number 5. Short-starved cells were obtained by starving with 1 % serum for 5 hours (h). Two hundred ninety-three HEK cells were grown in MEM alpha medium (Invitrogen) supplemented with 10% FCS (HyClone), 2 mM glutamine, 100 U/ml penicillin and 1 mg/ml streptomycin.
Recombinant human VEGF165 was obtained from PromoCell (Heidelberg, Germany) or Peprotech (London, England). Phorbol 12-myristate 13-acetate (PMA), citrated plasma and calcium ionophore A23187 were purchased from Sigma Chemicals (St. Louis, MO, USA). Cyclosporin A (CsA) was kindly provided by the Novartis Research Institute (Vienna, Austria). Polyclonal rabbit anti-EGR-1 and anti-GFP antibodies were from Santa Cruz Biotechnology (Santa Cruz, CA, USA) and New England Biolabs Inc. (Beverly, MA, USA), respectively. Peroxidase-conjugated donkey anti-rabbit immunoglobulin G (IgG) and sheep anti-mouse IgG were purchased from GE Healthcare Bio-Sciences (Little Chalfont, UK), Immobilon-P transfer membranes from Millipore (Bedford, MA, USA) and LumiGLO chemiluminescent reagent from New England BioLabs.
For the construction of a recombinant adenovirus expressing N-terminal Flag-tagged DSCR1 splice form 1, a human full-length DSCR1 cDNA for splice form 1 (clone IRALp962A2315Q2, RZPD – Heidelberg, Germany) was sub-cloned into the vector pACCMVpLpASR+ (5). For this purpose a 637-bp fragment was amplified by PCR and inserted between the BamHI and HindIII sites of the polylinker. The forward primer providing a BamHI site and encoding an N-terminal Flag-tag (27) was 5′-CGGGATCCATGGACTACAAGGACGACGATGACCAAGGAGGAGGTGGACCTGCAGGAC-3′, the reverse primer including a HindIII site was 5′-CCCAAGCTTTCAGCTGAGGTGGATCGGCGT-3′. The NAB2-expressing adenovirus and the control adenovirus without insert have been described previously (5). Production of high-titer virus stocks was performed as reported in reference (5). For infection HUVEC grown in six-well plates for two days were incubated with the recombinant adenoviruses for 24-48 h at a multiplicity of infection (MOI) of 100.
Cells were seeded in six-well plates at 70% confluency and grown overnight. Following treatment with growth factors or other reagents, cells were scraped from the plates and analyzed for TF activity as described (7). Briefly, after induction for 6 h with VEGF or EGF cells were washed twice and then scraped in 1 ml clotting buffer (12 mM sodium acetate, 7 mM diethylbarbitate and 130 mM sodium chloride; pH 7.4). 100 μl of resus pended cells were mixed with 100 μl of citrated plasma and clotting times were measured after recalcification with 100 μl 20 mM CaCl2 at 37°C. TF equivalents were determined by using a standard curve established with rabbit brain thromboplastin.
After incubation with the indicated stimuli, cells were treated with RNAlater (Ambion, Austin, TX, USA), washed once with DEPC-treated water and processed for RNA isolation. RNA was extracted from cultured endothelial cells with Trizol (Invitrogen). Two μg of total RNA were reverse transcribed into cDNA (SuperscriptTM II RT, Invitrogen) using oligo-dT primers and real-time PCR was used to monitor gene expression using a Light Cycler instrument (Roche Diagnostics GmbH, Mannheim, Germany) according to established procedures (28, 29). As internal standard the amount of β2-microglobulin mRNA was used for normalization. The oligonucleotide primers used were as follows:
TF-forward: 5′-CCGAACAGTTAACCGGAAGA-3′, TF-reverse: 5′-TCAGTGGGGAGTTCTCCTTC-3′; EGR-1-forward: 5′-AGCCCTACGAGCACCTGAC-3′, EGR-1-reverse: 5′-TGGGTTGGTCATGCTCACTA-3′; DSCRl_E4-forward: 5′-TTAGCTCCCTGATTGCCTGT-3′; DSCRl_E4-reverse: 5 ′-GGAGAAGGGGTTGCTGAAGT-3′; DSCR1-forward: 5 ′-GCCAAATTTGAGTCCCTCTTT-3′; DSCR1-reverse: 5 ′-GGTCGCATCTTCCACTTGTT-3′; β2-microglobulin-forward: 5′-GATGAGTATGCCTGCCGTGTG-3′; β2-microglobulin-reverse: 5′-CAATCCAAATGCGGCATCT-3′.
After the various treatments, cells were washed twice with ice-cold phosphate-buffered saline (PBS), lysed in 100 μl of Laemmli buffer, scraped and heated for 5 minutes (min) at 95°C. Total cell lysates were subjected to SDS-PAGE and the separated proteins transferred to Immobilon-P membranes according to described procedures (30). For staining, the membranes were blocked for 30 min with PBS containing 0.1% Tween-20 and 3% skim milk and incubated with the primary antibody diluted in blocking buffer for 1 hat room temperature (RT). Then the membranes were washed three times for 5 min with PBS containing 0.1% Tween-20 and incubated with peroxidase-conjugated secondary antibody for 1 h at RT After a washing step, the membranes were incubated for 1 min with ECL reagent (GE Healthcare Bio-Sciences) and exposed to X-ray films as required. For reprobing with an additional antibody, the membranes were washed twice in PBS, stripped for 30 min at 55°C with stripping buffer (62.5 mM Tris-HCL, pH 6.8, 2% SDS, 100 mM 2-mercaptoethanol) and washed three times for 5 min with PBS at RT. The membrane was stored wet wrapped in SaranWrap at 4°C after each immunodetection.
Two hundred ninety-three HEK cells were grown in six-well plates to about 70% confluency, and calcium phosphate transfection was performed with the expression constructs for EGR-1-myc, GFP-NFAT or a combination of both plasmids. The construct for the expression of human EGR-1 was obtained in the pcDNA 3.1/myc vector, which provides for the addition of a C-terminal myc-tag (Invitrogen, Carlsbad, CA, USA), by ligating a PCR product encompassing the coding region of the human EGR-1 gene including the single intron into the vector (31). The expression vector for a GFP-NFAT fusion protein (N-terminal pRSGFP-C1-NFATc) was kindly provided by L. Gerace (32). Twenty-four h post-transfection the cells were treated for 1 h with PMA (100 nM) or A23187 (2.5 mM). Then the cells were lysed for 20 min in 500 μl IP-lysis buffer (50 mM HEPES pH 7.3, 150 mM NaCl, 1 mM EDTA, 1% Triton X-100) containing protease inhibitors (PMSF, TPCL and TLCK) and the lysate centri fuged for 10 min at 15,000 rpm. For immunoprecipitation 2.5 μg rabbit polyclonal anti-myc antibody and 50 μl washed protein A Sepharose beads were added to 400 μl cleared cell lysate. Immunoadsorption to the protein A Sepharose beads was performed o/n at 4°C. The beads were then washed five times in NP40 IP-buffer (50 mM Tris pH7.5, 150 mM NaCl, 1 mM EDTA and 0.25% NP-40), the bound proteins solubilized in Laemmli buffer and analyzed by Western blotting.
Reporter gene constructs containing a fragment of the TF promoter (−330 to +118 bp) cloned into the luciferase expression vector pUBT-luc were previously described (18). Transient transfections of HUVEC were performed using the Lipofectamine Plus™ reagent (Invitrogen). Twenty-four h prior to transfection, HUVEC were seeded in six-well tissue culture plates to reach 70% confluency the next morning. Cells were incubated with transfection mixture containing a total of 1.5 μg DNA of the various cotransfected plasmids (including a CMV-β-gal or a TK promoter driven renilla-luciferase construct as internal control), 6 μl Plus™ reagent and 3 μl Lipofectamine in a total volume of 1 ml medium 199 per well for 2 h. Then cells were washed and incubated in M199 medium and 20% serum for 20-30 h before the treatment of the cells with growth factors or other reagents. Cells were lysed and luciferase values determined from triplicate wells and normalized to β-galactosidase produced from cotransfected expression plasmids. Several identical experiments were performed with plasmids from different DNA preparations to exclude an influence of DNA quality. In some cases the dual-luciferase® reporter assay system was used. Cells were then lysed for 20 min in ice-cold passive lysis buffer and measurement of firefly- and renilla-luciferase activity was performed on a luminoscan. Reagents and components of the dual-luciferase reporter assay system were purchased from Promega (San Luis Obispo, CA, USA).
Endothelial cells were seeded on LabTek 8-well tissue culture chamber slides (NUNC, Wiesbaden, Germany) coated with fibronectin. The cells were rinsed briefly in PBS and fixed in 3% paraformaldehyde or 3.7% formaldehyde/2% sucrose. Permeabilization was achieved by addition of PBS containing 0.25% Triton X-100. EGR-1 specific rabbit antibody were diluted in PBS/0.5% BSA and incubated for 2 h at RT The cells were washed three times in PBS/0.5% BSA. Secondary FITC-conjugated anti-rabbit antibodies (Accurate Scientific, Westbury NY, USA) were used for visualization. Cover slips were mounted in FA mounting fluid (BD Diagnostics, Franklin Lakes, NJ, USA) and results analyzed on a Nikon Diaphot TMD microscope. Images were taken by a CCD camera (Kappa GmbH, Gleichen, Germany).
To show significance of the data obtained p-values were calculated by Student's t-test. Statistical significance was assumed if the two-tailed p-value was <0.05.
In an attempt to define signaling pathways characteristic for VEGF/VEGFR-2 we compared VEGF and EGF in their ability to upregulate TF expression in endothelial cells. When HUVEC were activated with VEGF a strong increase in TF mRNA, and protein expression was observed, whereas treatment with EGF failed to induce significant TF expression (Fig. 1A, B). According to our previous data, EGR-1 is decisively involved in the VEGF-mediated upregulation of TF, since deletion of the EGR-1 sites from the TF promoter abrogates VEGF-mediated induction of TF reporter genes (6, 7) and an adenovirus overexpressing the specific corepressor of EGR-1, NAB-2, strongly inhibited the VEGF effect on TF mRNA (5).
However, when we next tested whether the inability of EGF to induce TF induction would be reflected in a diminished capacity of EGF to trigger EGR-1 production, we observed that EGF was at least as efficient as VEGF in the induction of EGR-1 mRNA and protein (Fig. 1C, D). It appeared therefore that another pathway selectively induced by VEGF would be important in addition to EGR-1 to activate the TF gene. One of the candidate pathways, which is critically involved in the regulation of TF by inflammatory mediators, the NF-κB pathway (18, 20), was excluded since according to our previous data VEGF did not cause significant activation of this pathway (6, 7) and overexpression of IκB, the natural inhibitor of NF-κB, had no strong inhibitory effects on TF upregulation in response to VEGF (data not shown). IκBα overexpression by adenoviruses had been previously shown to largely abrogate TF induction by TNF-α (20).
Based on previous data that NFAT can bind to and activate the TF promoter (33), we investigated the quantitative contribution of Ca++ signaling and NFAT activation to TF upregulation by VEGF. For this purpose we used the calcineurin inhibitor cyclosporin A (CsA). The obtained data show that VEGF-mediated upregulation of TF mRNA and protein expression was inhibited by CsA to an extent of about 50% and 40% supporting a significant contribution of this pathway to TF upregulation (Fig. 2A, B). To confirm that Ca++ signals can upregulate TF, we further tested the induction of TF by the Ca++ ionophore A23187 and its inhibition by CsA. TF mRNA and protein was strongly induced by the Ca++ ionophore and CsA inhibited this induction by about 80 and 50% (Fig. 2A, B). Usually ionophore induction reached only levels of about 30–50% of the VEGF-mediated induction (data not shown). This and the stronger inhibition of the A23187 effect by CsA when compared to the inhibition of the VEGF induction suggests that, in the case of VEGF, pathways in addition to calcineurin/NFAT have an important role in the induction. This is further supported by the finding that when the Ca++ chelator BAPTA-AM is used to inhibit Ca++ signals, the effects of the Ca++ ionophore are almost completely inhibited whereas the VEGF effects again are inhibited only partially by about 30% (Fig. 2C).
To test whether NFAT induction might be a substantial difference between VEGF and EGF signaling and would be significantly blocked by CsA in endothelial cells, we transfected HUVEC with an expression vector for an NEAT-GFP fusion protein (32). One day after transfection the cells were stimulated with VEGF, A23187 or EGF in the presence or absence of CsA. Then the cytoplasmic-nuclear translocation of NEAT was analyzed by immunofluorescence. The obtained data showed that upon stimulation with VEGF and ionophore, NFAT translocated rapidly to the nucleus within 30 min, and this translocation could be largely inhibited by preincubation of the cells with CsA (Fig. 3A). In contrast, no stimulation of translocation could be observed for EGF, which obviously is not competent to induce Ca++ signals and NFAT translocation. When parallel control samples were stained for EGR-1, a rapid synthesis and nuclear accumulation of EGR-1 after 45 min was revealed in VEGF-as well as in EGF-treated samples (Fig. 3B). These data support that the specific calcineurin-dependent activation and nuclear translocation of NFAT by VEGF might be a relevant factor for the selective activation of certain genes by VEGF, which can not be induced by some other growth factors such as EGF in endothelial cells.
To show that the inhibition observed at the mRNA and protein level is due to reduced TF gene transcription, we further examined the effects of CsA on a TF reporter gene. HUVEC were transfected with the reporter gene containing the −330/+118 bp TF promoter element fused to a luciferase reporter construct (18). In this assay, TF promoter transactivation was upregulated five-fold when cells were treated with VEGF. Comparable to the reduction in TF mRNA and protein levels, the induction of the reporter gene by VEGF was inhibited by preincubation with CsA by about 50–60%. PMA/A23187-induced transcription was similarly affected suggesting that indeed a significant portion of the VEGF stimulation of the TF promoter can be mediated through the Ca++/calcineurin/NFAT pathway (Fig. 4A).
We further analyzed the individual capacities of EGR-1 and NFAT to transactivate the TF promoter. For this purpose expression plasmids for EGR-1 or NFAT and combinations of both were transfected into HUVEC. These experiments showed that overexpression of EGR-1 alone was sufficient to transactivate the –330 bp reporter gene up to six-fold. In contrast to EGR-1, NFAT overexpression only slightly, although significantly (p < 0.02 vs. control), induced the TF promoter reporter gene. However, co-expression of both transcription factors resulted in synergistic transactivation of the promoter. In several independent reporter gene experiments on average an 11-fold upregulation of the luciferase gene driven by the tissue factor promoter was revealed (Fig. 4B). These data provide evidence for a cooperative transactivation of the TF promoter by both factors, although it appears that EGR-1 plays a predominant role in the in-vitro reporter assay.
Since the reporter gene assays revealed a functional interaction of EGR and NFAT in endothelial cells it seemed possible, that these two proteins might also interact physically with each other. To test this possibility, myc-tagged EGR-1 and the GFP-NFATc fusion protein were overexpressed in human epithelial kidney 293 cells (293 HEK). Assuming that PKC activation and intracellular Ca++ signals might lead to modifications of EGR-1 and NFAT supporting interactions, samples of the cells were also treated with PMA and calcium ionophore A23187. Co-immunoprecipitations were then performed with extracts from the un-induced and PMA/ionophore-induced 293 HEK cells. The precipitated proteins were analyzed on immunoblots with GFP- and EGR-1-specific antibodies. The obtained data show the presence of GFP-NFATc in immunoprecipitates of EGR-1-myc from uninduced and induced lysates (Fig. 4C); however, no significant increase of GFP-NFATc appeared to be present in immunoprecipitates from PMA/A23187-induced lysates. The sizes and levels of expression of EGR-1-myc and GFP-NFATc in total cell lysates are shown for control purposes in the right panel of Figure 4C. These data suggest that in addition to the binding to their respective specific binding elements in the tissue factor promoter a physical interaction between NFAT and EGR-1 provides a basis for their functional cooperation in endothelial cells. A similar interaction has been proposed to occur during the regulation of the IL-2 and TNF-α genes in T lymphocytes (34, 35).
Recent microarray data obtained by us and other laboratories have identified DSCR1, a gene encoding a protein with calcineurin inhibitory function, among the most highly VEGF-upregulated genes in endothelial cells (21, 22; B. Schweighofer and E. Hofer, unpublished data). DSCR1 spans nearly 45 kb of genomic DNA and comprises seven exons, four of which (exons 1–4) are alternative first exons (36). Since our data from Affymetrix microarray analysis had further indicated that DSCR-1 splice variant 4 (Calcipressin 1 isoform c) is, similar to TF, selectively upregulated by VEGF but not by EGF, we included DSCR1 in this study. The data obtained with real-time RT-PCR showed that VEGF strongly induces the DSCR1 exon 4 splice form (DSCR1_E4) mRNA with kinetics similar to TF up to 80-fold, whereas mRNA levels after EGF treatment are nearly unchanged (Fig. 5A). In contrast to TF induction, this upregulation was almost completely inhibited by CsA supporting that the exon 4 splice variant of the DSCR-1 gene is upregulated by VEGF predominantly via the calcineurin/NFAT pathway (Fig. 5B). A corresponding promoter element containing several NFAT binding sites has previously been identified upstream of exon 4 of the DSCR-1 gene (26). These data further support that NFAT activation is important for the upregulation of a group of genes by VEGF, which are not influenced by EGF.
Since DSCR-1, also known as calcipressinl or MCIP1 (modulatory calcineurin interacting protein 1), has been shown to bind to and inhibit the enzymatic activity of calcineurin (23, 25), we have further constructed recombinant adenoviruses expressing DSCR1. To be able to monitor the endogenous DSCR1_E4 splice form, which is regulated by VEGF, adenoviruses for expression of DSCR1 exon 1 splice form (DSCR1_E1) were prepared. Splice form 1 is not regulated by VEGF and is only expressed at very low levels or absent from endothelial cells ([21]; B. Schweighofer and E. Hofer, unpublished data). Overexpression of DSCR1_E1 was then tested for its effects on VEGF-mediated upregulation of TF and endogenous DSCR1_E4 (Fig. 5C, D). The obtained data show that DSCR1_E1 overexpression prevented induction of DSCR1_E4 mRNA by VEGF as well as A23187 almost completely. This demonstrates that the calcineurin/NFAT pathway is predominantly important for DSCR1_E4 induction. In the case of TF mRNA the A23187-mediated upregulation was reduced by 90%, the inhibition of the VEGF regulation resulted on average in reductions of about 50% similar to the CsA inhibition. However, when adenoviruses expressing the corepressor NAB2 where used in addition to DSCR1_E1 viruses, TF mRNA induction was nearly completely inhibited. This supports the importance of both, the NFAT and EGR-1 pathways, for TF induction.
The individual members of the endothelial-specific growth factor receptor families including the VEGF, Tie and ephrin receptors as well as some other receptors present on many different cell types, such as the EGF receptor, are receptor tyrosine kinases and possess multiple tyrosine residues in their cytoplasmic domain. These are in part phosphorylated upon activation by their specific ligands and then function as specific docking sites for molecules initiating cytoplasmic signaling cascades (2). Since the different receptor tyrosine kinases elicit to some degree overlapping, but also distinct responses in endothelial cells, part of the signals generated from the different receptors presumably differ from each other. In the case of the VEGFR-2 the cytoplasmic domain contains 19 tyrosines (1, 37, 38) and their differential degree of phosphorylation and functioning as docking sites for different signaling molecules leading to the activation of distinct signaling pathways is currently intensively investigated.
Since we have identified the TF gene as the example of a gene strongly upregulated by VEGF (6, 7), but to a lesser degree or not at all by some other tyrosine kinase receptors such as the EGF receptor (see Fig. 1), we have investigated the intracellular signals leading to this selective induction. The VEGF-A-mediated upregulation, as previously shown, is mainly mediated via VEGFR-2, since isoforms of VEGF selectively binding to VEGFR-2 can upregulate TF comparable to VEGF-A (7, 39) and P1GF, which specifically binds to VEGFR-1, only marginally affects TF ([40]; G. Schabbauer and E. Hofer, unpublished data).
TF is an important component of the repair mechanisms of vascular cells and as primary initiator of the blood coagulation cascade ensures the structural integrity of damaged vessels after inflammatory and/or mechanical injuries (8, 9). However, it seems to be a molecule of dual functions, to be also important for later stages of tissue repair such as wound healing (9, 41) and to have a regulatory role in the formation of new vessels (12, 15). TF has been directly implicated in vasculogenesis (14), as well as in tumor angiogenesis (13, 16, 41). The available evidence suggests that TF contributes to these processes by induction of intracellular signaling directly through its cytoplasmic domain and indirectly via factor Vila-dependent PAR-2 activation (9, 15, 42). In endothelial cells the duality of its function seems to be reflected by its upregulation by inflammatory mediators and by VEGF-A.
We have previously identified the transcription factor EGR-1 as a relevant factor involved in the induction of the TF gene by VEGF-A (7). Induction of TF and EGR-1 by VEGF was further dependent on the MAP kinases MEK/ERK and on PKC, since TF induction could be largely inhibited by the respective inhibitors of MEK and PKC, PD098059 and bis-indolylmaleimide (6). Overexpression of NAB2, a specific corepressor of EGR-1, strongly inhibited VEGF-A-mediated TF upregulation supporting the important role of EGR-1 (5). However, since EGR-1 is induced to a similar extent by EGF and VEGF, it seems that although EGR-1 is obviously essential for a significant part of the VEGF induction, in the form induced by EGF it is not sufficient to mediate upregulation of the endogenous TF gene. This differs from transcription studies using reporter gene assays, since in these assays cotransfections with EGR-1 expression plasmids alone can efficiently upregulate the TF promoter (5, 7).
Several lines of evidence suggested that VEGFR-2 is very effective in recruiting and activating PLC-γ and the downstream Ca++ and PKC signaling pathways (37, 43, 44) including our previous results that EGR-1 induction by VEGF is largely PKC-dependent and could be inhibited by PKC inhibitors (6). It seemed therefore plausible that the induction of the Ca++ signaling pathway leading to calcineurin activation, NFAT dephosphorylation and cytoplasmic-nuclear translocation, might be required for efficient TF upregulation. On the other hand, we speculated that EGF would insufficiently trigger the activation of this pathway. We show here that this indeed is the case. VEGF triggered the rapid cytoplasmic-nuclear shuttling of an NFAT-GFP fusion protein, whereas EGF was completely inefficient. The specific calcineurin inhibitor CsA as well as the Ca++ chelator BAPTA-AM significantly inhibited TF upregulation by VEGF to about 50%. Furthermore, the Ca++ ionophore A23187 strongly upregulated TF, demonstrating that the Ca++ signals alone can trigger TF upregulation.
Since these data supported that EGR-1 and NFAT are both contributing to full TF induction by VEGF, we investigated a potential direct cooperation between the two factors in reporter gene assays and by coimmunoprecipitation. In the reporter gene assay EGR-1 alone caused a significant upregulation and the combination of EGR-1 with NEAT displayed a synergistic effect (Fig. 4B). By itself NEAT only slightly increased promoter activity suggesting that the factor alone is not effective to cause strong TF upregulation but requires the presence of EGR-1. It is important to note that the NFAT consensus sequence within the TF promoter significantly overlaps with the NF-κB binding site (33). In case of stimulation of the cells with suboptimal doses of VEGF and TNF-α, NFAT induced by VEGF and NF-κB induced by TNF-α might additively contribute to TF expression, whereas in excess of both factors they are likely to compete for binding to the composite NF-κB/NFAT DNA binding site. Coimmunoprecipitations performed with overexpressed NFAT and EGR-1 support the idea that the functional cooperation between the factors is based on a physical interaction. It is possible that EGR-1 and NFAT by interacting with each other mutually increase their binding to the respective promoter elements or synergistically increase their potential to promote transcription initiation, as it is supported by the reporter gene studies. This hypothesis is in accordance with previously published reports, describing direct cooperative interactions and stable physical protein complexes between EGR-1 and NFAT important in the activation of the IL-2 and TNF-α promoters in T cells (34, 35, 45).
In regard of the role of the Ca++ signals for VEGF-mediated gene regulation it is of importance that recent data from differential screens and microarrays have identified the calcineurin inhibitor DSCR-1 as one of the most highly VEGF upregulated genes (21, 22). Our own Affymetrix data confirmed by RT-PCR have defined DSCR-1 and TF in atop group of the 20 most highly VEGF-upregulated genes in relative terms. Both display an over 30-fold upregulation of mRNA when compared to uninduced cells. In contrast to TF, DSCR-1 belongs also in the absolute amount of mRNA produced to the top group (Schweighofer et al., manuscript in preparation). Several splice forms of the DSCR-1 protein have been shown to bind to calcineurin and to inhibit its phosphatase activity preventing the activation of NFAT (46). The regulatory importance of DSCR-1 for Ca++ signaling is shown by the multiple disease manifestations primarily in trisomy 21 (24) connected to inappropriate expression of the protein. In addition, chronic overexpression of DSCR-1 was on the one hand linked to Alzheimer disease (47), but on the other hand protected against cardiac hypertrophy in animal models (48) supporting the importance of a disturbed NEAT/DSCR-1 balance in these diseases. The strong induction of DSCR-1 by VEGF seems to result in a negative feedback loop to limit the Ca++/calcineurin component of VEGF signaling and therefore potential harmful effects of excess and prolonged NFAT activation.
We have therefore used the DSCR-1 gene as a second example to test for the importance of the calcineurin/NFAT pathway for VEGF-mediated gene regulation. The obtained data on the one hand clearly show that NFAT is the predominant factor in VEGF-mediated DSCR1_E4 promoter regulation. DSCR1_E4 mRNA is upregulated to a similar extent by VEGF and A23187 and both inductions could be strongly inhibited by CsA or DSCR-1 overexpression. The inability of EGF to trigger DSCR1_E4 induction further suggests that the activation of the calcineurin/NFAT pathway by VEGF could be the primary basis for the induction of a wider spectrum of genes by this factor. Our data indicate that NFAT induction could be important for a significant portion of the VEGF-mediated gene regulation and provide the factor with unique properties when compared to other growth factors not triggering this pathway to the same extent. It is intriguing, that a single tyrosine residue in VEGFR-2, Y1175, was previously found to be essential for PLC-γ activation (43, 49) and downstream calcineurin/NFAT activation. Whereas certain genes, such as DSCR-1, might be predominantly regulated by NFAT, others, such as TF, may require the combination of EGR-1 with NFAT and/or possibly other factors to be determined. Based on the obtained data it might be possible that combined inhibition of both, the calcineurin/NFAT and the EGR-1 pathways might be worthwhile to be explored for more effective inhibition of VEGF-mediated gene expression and angiogenesis than it was shown already for the inhibition of the individual pathways (5, 21).
We are grateful to L. Gerace for a gift of pRSGFP-Cl-NFATc. Further we thank our colleagues from the Department of Vascular Biology and Thrombosis Research for help and discussions during the course of these studies. This work was supported by grants to E.H. of the Austrian Science Fund (NFN94–3) and the European Commission (LSH-CT-2005–518178).
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


text:
Log In
Add Home
Sign Up
Mountaintop Modern
A couple's investment of sweat equity pays dividends in a mountainside house in southwestern...
Top 5 Saul Bass Movie Titles
In our February issue, on newsstands now, we celebrate the life and work of the great graphic designer Saul Bass on the...
10 Cozy Wood-Burning Stoves For Riding Out the Last Bit of Cold Weather
Wood-burning stoves aren't just for rustic cabins in the woods anymore.
What's Your Favorite Book on Design or Architecture?
Replenish our "to-read" lists with your favorite titles on design or architecture.
Steel and Magnolias
What sort of house might a man with the title "recycling coordinator" live...
12 Functional Modern Home Libraries
It's often said that rooms are furnished by books.
Bookshelf Basics
Classic or contemporary, these titles are guaranteed to appeal to burgeoning bookworms of the modernist sort.
Putting Industrial Style Design into Your Living Space
How adding industrial style furnishings can bring a bit of factory floor to your decor.
10 Brewpubs That Have Tapped the Art of Modern Design
Enjoying a bit of conversation over a beer is a pastime that goes back centuries, and today, new iterations of the proverbial...
On a Rock in a Hard Place
In an unlikely mountaintop locale, Anderson Anderson Architecture crafted a home out of a complex composition of off-the-shelf...
8 Iconic Houses in Palm Springs, California
With its short distance from Los Angeles, Palm Springs is a popular locale for those looking to escape the urban sprawl for a...
Beach Reading
Looking for a little light literature to while away the hours? We suggest a quartet of (fictional) titles for the design minded.
Bacteria take a Bite out of Messy Manufacturing of High End Products
Anodizing aluminum has gotten a bit of a bad rap in the environmentally conscious community...Until now.
Friday Finds 06.08.12
Have a look at three of our favorite finds from the week: candy architecture, painting the streets, and a bit of cyberwarfare.
Striking a Cord
British artist Maisie Broadhead elevates the nuisance of an unsightly lamp cord to over-the-mantel art with this clever bit of...
Friday Finds 10.22.2010
The Dwell team was heavily inspired by art and photography this week.
Roger Federer's Personal Logo?
If you put any stock at all in national stereotypes--we Americans are a bit pudgy, I confess--then you're no stranger to the...
A Couple Tackles Conversion Challenges and Builds a Modern Renovation
To convert a musty mid-century house with a nonsensical floor plan into a modern and space-efficient family home, three intrepid...
Tips For Organising Your Office Secret Santa!
At this time of year, as a business you might be looking for a few ways to bring the festive cheer into your office; well, look...
Passive Progressive
Among the first Passive Houses in France, this bamboo-clad farmhouse by the Parisian firm Karawitz Architecture brings a bit...
Dwell Life © 2017
Advertise on Dwell
Order Back Issues


text:
Relevant offers
2013 was a great year for the average investor, but few market strategists believe that 2014 will be as good. The simple strategy of buying US stocks, selling bonds and staying out of international markets isn't going to work as well as it has, they say.
Some of Wall Street's biggest money managers have come up with a few resolutions to help investors:
Few investors expected 2013 to be as big as it was. The S&P 500 index is up 28 per cent for the year, its best year since 1997. Including dividends, it's up 30 per cent.
On average, market strategists expect 2014 to be somewhat tame. Most are looking for the S&P 500 to rise to 1,850 to 1,900 points, a gain of just 2 to 4 per cent.
Investors bid up stock prices to all-time highs this year, despite a mediocre economy and corporate profits that were less than spectacular.
At the beginning of 2013, the price-to-earnings ratio on the S&P 500 was 13.5, meaning investors were paying roughly $13.50 for every $1 of earnings in the S&P 500. Now the S&P 500's P-E ratio is around 16.7.
While a P/E ratio of 16.7 won't set off any alarm bells - the historical average is 14.5 - it is noticeably higher than it was a year ago.
Investors have high expectations for corporate profits, based on the prices they are paying.
"It's hard to believe that this market can go much higher from here without some corporate earnings growth," said Bob Doll, chief equity strategist at Nuveen Asset Management.
Profit margins are already at record highs, and corporations spent most of 2013 increasing their earnings by cutting costs or using financial engineering tools like buying back their own stock.
Earnings at companies in the S&P 500 grew at an 11 per cent rate in 2013. The consensus among market strategists is that profit growth will slow to around 8 per cent in 2014.
However, if the US economy continues to improve, and corporate profit margins expand, it could justify the prices investors have been paying for stocks.
Be wary if your neighbour decides to jump head-first into the market.
A large number of investors have remained on the sidelines for this five-year bull market. Since the market bottomed in March 2009, investors pulled US$430 billion (NZ$523b) out of stock funds, according to data from Lipper, while putting nearly US$1 trillion into bond funds.
Professional market watchers are concerned that many individual investors, trying to play a game of catch-up, might rush into the market. The surge of money could cause stocks to jump if investors ignore warnings that the market is getting overvalued.
Wall Street calls this phenomenon a "melt-up." As you can guess, a "melt-up" could lead to a "melt-down," as happened in the late 1990s with the dot-com bubble.
"I fear people, who sat out 2013, will jump in too fast next year and get burned," said Richard Madigan, chief investment officer for JPMorgan Private Bank.
Which leads us to:
Stocks cannot go higher all the time. Bearish investors have been saying for months that stocks are due for a pullback in the near future.
The S&P 500 is up 66 per cent since the stock market's last major downturn in October 2011. It has been resilient through several scares this year, including the conflict in Syria, the budget crisis and near-breach of the nation's borrowing limit in October.
In their 2014 outlook, Goldman Sachs analysts said that while the market has been strong, they see a 67 per cent chance that stocks will decline 10 per cent or more in 2014, which is known as a stock market "correction."
Goldman analysts still expect stocks to end the year modestly higher.
Fixed-income investors had a tough year in 2013. The Barclays Aggregate bond index, a broad composite of thousands of bonds, fell 2 per cent. Investors in long-term bonds were hit even harder, losing 15 per cent of their money since the beginning of the year, according to comparable bond indexes.
2014 is not looking good for bond investors, either.
The Federal Reserve has started to pull back on its bond-buying economic stimulus programme. That means one of the biggest buyers of bonds for the last year will slowly exit the market this year.
The exit could send bond prices falling.
"Bonds are hardly a place to be in 2014," Nuveen's Doll said.
That doesn't mean investors should avoid bonds altogether, strategists say.
Instead, investors should reorganise their portfolio to focus more on bonds that mature in relatively short periods of time. The prices of those bonds tend to fluctuate less than those of bonds that take longer to mature, and are less likely to lose value when interest rates rise, as many expect will happen .
Madigan said that under normal circumstances he would advise investors to hold bonds that mature in an average of about five years. This measure is referred to as a bond's "duration".
For 2014, Madigan is advising investors to restructure their portfolio to have an average duration of two to two-and-a-half years.
"Long duration bonds are much more a riskier asset than a safe asset next year," Madigan said.
Other than stocks, the average investor typically has access to three other types of investments: cash, bonds and commodities such as gold.
None are expected to perform better than the stock market this year.
If bonds had a tough 2013, gold investors got punched in the stomach. Gold is down 28 per cent this year, and is on its way to its first annual loss since 2000.
Gold is expected to have another tough year, with inflation under control and the Fed expected to gradually exit the bond market. Analysts at Barclays Capital expect gold to end 2014 at $1,270 an ounce, about 6 per cent higher than where it is today.
Cash is expected to provide a near-zero return next year. Savings and money market-accounts are returning less than 0.1 per cent on average.
Several market strategists believe international stocks will be the place to be. Asian and European stocks did not perform as well as US stocks in 2013, with the exception of Japan, where the Nikkei 225 index soared 53 per cent.
Europe is particularly attractive, they say. The European Union came out of a two-year recession in 2013, and the debt crisis that plagued most of the region has abated. Some strategists say that Europe is a couple of years behind the US in its economic recovery, and stocks could be relatively cheap.
"The big debate among my team is whether international markets will play catch-up next year," said Madigan of JPMorgan Private Bank. AP
Sponsored links
Financial personal training: a diet for your bank account
Ignore the kiwi on the tin: World-famous Kiwi shoe polish is 100 per cent Australian
New Zealanders reluctant to change to a new bank
New skincare firm offers buyers chance to indulge - and help
Fresh As way to grow a company
Potential buyers asked to help design Timaru's Bay Hill Development
No regrets for elderly who tap their homes equity
Reverse mortgages prove costly blessing to cash-strapped elderly homeowners
Documents reveal bitter aftertaste after Dunedin Cadbury factory closure announcement
RSE workers made 'scape goats' over housing affordability
Damien Grant: The long slow decline of The Truth has ended on my mezzanine floor
Posh grocery chain Farro Fresh may expand nationwide
Stacey Kirk: Steven Joyce slams cash-laden briefcase on table - no room for a sly envelope
Newmarket business awards pulls in highest number of entries
Dean Barker's men miraculously dodge injury in 'ugly' America's Cup collision with Ben Ainslie
A fridge that orders the groceries, a two minute dishwasher and a solar skin: Welcome to the homes of the future
British police release new photos of Manchester attacker from night of deadly bombing
50 firefighters at 'suspicious' south Auckland commercial building blaze
Man dies at King's College, Auckland
Fashionable dogs facing a life time of misery, vet association warns
College with low roll tackles perception problems on Auckland's North Shore
'Vague' timeframe for urgent $70 million upgrade to Auckland bottleneck Lake Rd
New Zealand hairdresser of the year wins for his collection of grungy styles
Overcrowding forces Auckland schools to get creative to find teaching spaces
Gents, please stop wearing activewear everywhere
Hollywood's leading ladies stage red-carpet rebellion at Cannes
North Shore woman granted dying wish to see Southern Lights with family
Why are the coldest and darkest countries always the happiest?
German bikini model goes to extremes for the perfect picture
One lucky winner is $27m richer after Lotto's Powerball jackpot struck
Deja vu? Oracle come from behind to beat Team New Zealand in America's Cup thriller
Recap: 35th America's Cup qualifying series - race day one
Schapelle Corby arrives in Australia after last-minute flight change to avoid media
Police charge father of toddler swept away with two counts of dangerous driving causing death
Police find bodies of mother and daughter whose disappearance left small town 'mystified'
Dean Barker's men miraculously dodge injury in 'ugly' America's Cup collision with Ben Ainslie
The Hurricanes go deep into the well to beat Bulls in Pretoria
Crusaders teach Rebels a Super Rugby lesson in Melbourne
Kiwis stuck after computers cause chaos at London's Heathrow and Gatwick airports


text:
M14 50-Round Drum Magazine
The M14 50-Round Drum Magazine is a factory new magazine designed for the M14 and M1A series of rifles. This high quality magazine is made to hold and feed 50-rounds of .308 Winchester ammunition into your rifle and will do so as fast as you can pull the trigger. The design of this drum magazine has been perfected by X Products and brought to virtually all 7.62x51 rifles and now is available for the M14.
Availability: Out of stock
The M14 and M1A series of rifles have been popular with collectors and shooters for decades. With the M14 seeing service in the US military, the interest in owning one of these historic rifles has only increased over time. The Springfield M1A has given legions of enthusiasts the opportunity to own a rifle that is very much like the M14, with the main difference being the lack of a selector switch for full-auto fire.
With the new M14 50-Round Drum Magazine by X-Products, you can increase the available firepower of your M14 or M1A rifle. This premium drum magazine holds 50-rounds of 7.62x51 (308 Winchester) ammunition and is ready to feed your prized rifle as quick as you can pull the trigger. The additional capacity this drum magazine provides will result in more fun at the shooting range and increased trigger time for better marksmanship training.
- Factory New M14 / M1A Drum Magazine
- 50-Round Capacity
- Low Profile Design
- Fits M14 and M1A Rifles
- Made in the USA
- Limited Lifetime Warranty from X-Products
|X Products
|Gun Model
|M14 Rifle, M1A Rifle
|Ban Status
|X Products
|.308 (7.62x51)
|Factory New
|50 Rounds
|No Sales To Restricted States
|Returns Accepted
|No - No Returns Accepted
Product Questions
Regular Price: $29.95
Special Price $10.95


text:
With natural history collections in decline, what's a busy researcher to do with specimens from past studies?
Read More
On the 70th anniversary of the first successful nuclear weapon test, we've collected a selection of articles and book reviews from American Scientist that cover this controversial topic from multiple angles.
Sigma Xi, The Scientific Research Society moved from Connecticut to North Carolina in 1990 to be in the heart of the Research Triangle. We're celebrating our 25-year anniversary of calling North Carolina home! Since then, we've experienced the state's vibrant scientific research and diverse landscapes, from the mountains to the sea.
In honor of the first week of summer, we're revisiting the book Cool: How Air Conditioning Changed Everything, by Salvatore Basile, with a collection of images as well as some additional discussion of the book. We like to think of it as the summertime-release, extended dance version of our original review.
I predicted that any insect that flies at night must have a way of dealing with their fiercest nocturnal predators—bats. More recent findings by Akito Kawahara of the University of Florida and my former graduate student Jesse Barber of Boise State University confirm this prediction in two exciting ways.
June 3 marks the 50th anniversary of the first American space walk, or Extravehicular Activity (EVA) in NASA terms. The technology and design of space suits—called Extravehicular Mobility Units in NASA parlance—has also evolved greatly over the past 50 years. In the September-October 2015 issue of American Scientist, we will feature an article from Dave Cadogan, Director of Engineering at ILC Dover, the only company that currently makes US space suits.
We recently published an article about the results of a 4.5-year program of research on gender's influence on faculty hiring preferences for tenure-track STEM assistant professorships. Our methods brought up an interesting issue about the types of adjectives used to describe job applicants, one that we did not have space to address in the paper.
It's doubtful we would have Earth Day without Rachel Carson. Her pioneering 1962 book Silent Spring sparked the environmental movement and infused ecological ideas into mainstream thinking. So to recognize this date, I combed through the archives of American Scientist to get a sense of how scientists have discussed Carson and Silent Spring over time.
For millennia, fundamental units of time were referenced this way. The ever-changing Earth rotation interval was divided into 86,400 seconds. But Earth rotation is not constant and is unpredictable. This meant that the duration of a second had to be changed occasionally to maintain essential synchronization with Earth rotation.
Drs. Oscar Schofield, Scott Glenn, and Mark Moline wrote about their research with autonomous underwater vehicles (AUV) in a past issue of American Scientist. Unfortunately, an AUV called Nereus experienced a catastrophic failure in May of 2014. Read the authors's tribute about this event.
A headline is designed to convey the gist of a story, and also entice a reader to want more information. But sometimes the headlines themselves can inspire the imagination. Resident cartoonist and Contributing Art Director, Tom Dunne, created some off-the-cuff doodles, based solely on the headlines from Sigma Xi's SmartBrief.
When I have the opportunity to review the older issues of American Scientist, I always find a few gems that seem to stand the test of time...Read more.
The annual Twitter event returns with 64 mammal species ready to fight to the virtual death for your entertainment and education.
Scans of implant patients deaf in only one ear, before and after the procedure, have uncovered how quickly the cortex can rewire itself.
The World Lemur Festival starts today, and is a great occasion to celebrate these charismatic primates—and their poop.
Receive notification when new content is posted from the entire website, or choose from the customized feeds available.
Copyright 2007 SIGMA XI. All Rights Reserved


text:
You have searched for Safari Books Online
LAST UPDATED : 27 May 2017, 22:21 IST
- Book clubs, interactive sessions tempt people to read more
Priyanka Bhatia Dehradun: "Books are a uniquely portable magic", said author Stephen King. It's a sentiment that finds resonance with many book lovers in Dehradun who are increasingly meeting to discuss their favourite authors and titles, as well as bibliophiles who are trying to inculcate the love of reading among the young generation which is hooked on to the digital medium. Neha and Rohan Raj, a young couple which started a book club 'Booknerds' in 2015, says that inculcating an interest in physical books was their priority when they started out. "We promote reading at schools, cafes and have author sessions for promotion of books too. We think that the pleasure of holding a real book in one's hand cannot be replaced and wanted more people to experience that pleasure. From 20 members when we began, we have now grown to over 100," said Neha. The couple usually conduct 2-3 sessions in a month which are referred to as Booknerds Hangouts. This month for instance, sessions have included reading from the works of Harivansh Rai Bachhan as well as a discussion on superhero comic books. Upendra Arora, owner of Natraj Book Stores, one of the oldest book shops in the Doon valley, who has started a campaign to get students of schools and institutions to read more, said that his objective was to spread the message that quality reading is important for every person, and to help more people experience the charm of reading books. "While the digital medium might provide information, spending too much time on it is harmful for the eyes. Dipping into a good book on the other hand is not only a knowledge enhancing activity but also therapeutic in many ways." The efforts made by these individuals to inculcate the book reading habit is slowly bearing fruit as more people especially youngsters get hooked on to the written word. Geetika Chauhan, a book lover told TOI, "Visiting book-stores and browsing through the many options available there is a charm that cannot compare with shopping for anything else. It is like visiting a candy store and being a kid all over again. Maybe, book stores should start giving membership cards for encouraging loyal customers and also gift free books on every landmark purchase to encourage the book reading habit further."
- DU won't hold online entrance exams for M Phil, PG programmes
The standing committee in a meeting held on May 19 had given approval for holding both online and offline exams for M Phil, PhD and PG programmes. It had attracted criticism from student circles, including the Delhi Union Student Union and the ABVP, who claimed that the online test could disadvantage students from rural areas.
- Rapper King JDs new song is out
Shreyas Jadhav aka King JD has recently launched a rap song titled Fakaat Party. The track perfectly blends together witty lyrics and high octane music. The rapper who also goes by the name King Jedi has made a name for himself in the industry. The music for this has been composed by Harsh, Karan and Aditya. Sujit Kumar has written the lyrics. Shreyas Jadhav had earlier produced a film 'Online Binline' and had used rap music in the song 'Oh Ho Kaay Jhala' rendered by Hariharan and Leslie Louis, which is still fresh in the memory of music lovers. He later got the limelight for his song 'Pune Rap' which talks about Pune city and in particular the historical Shaniwarwada.
- Man who collects clippings of 'toilet stories', in Limca Book
Many would say that 58-year-old Ramesh Bhateja's hobby is quite an odd one to have, that of collecting newspaper clippings on toilets, but the same has bagged him a mention in this year's Limca Book of Records (LMR), for collecting these pieces for over 20 years
- Engineering, pharmacy management quota admissions to go online
Management quota seats in engineering and pharmacy in Telangana may be filled through online admission process as the Telangana State Council of Higher Education (TSCHE) is contemplating to introduce the new system from academic year 2017-18.
- Postal department to keep track of postmen through GPS
CHANDIGARH: Now the postal department will keep a track on their postman's movement through GPS during delivery of the postal articles in the city. In fact as and when the postman delivers the article it will be updated on online system that where the product is delivered, by whom and on which address. There are 171 postmen of Chandigarh out of total 249 postmen who received the mobile phone on Tuesday. Postmen of Chandigarh, Mohali, Ropar and Nagal got mobiles from department of Punjab circle. The department has launched a postman mobile application for the Punjab circle area through which the tracking of the postman and article delivery can be traced by the higher officials. Earlier the system was updated at 6 pm in the evening after the postmen return from the field. The official said that the service has been launched as there are large number of complaints which the department received on day to day basis that the registered articles were not delivered by the postmen on the address mentioned on them. Radhika Dhir, Senior Superintendent Of Post Offices, Chandigarh Division today inaugurated Postman Mobile Application at the General Post Office, Sector-17, Chandigarh. She said that it will enable real time up-gradation of delivery information at the point of delivery itself. This will help the customers to track their consignments. Postmen staff were given Subscriber Identification Module (SIMs) to use this application for which the training has already been imparted to them.
- Teacher sets record for alphabetical collection of comic books
With a penchant for setting a new record after another, city school teacher Ninad Jadhav, 39, recently set a national record for a one-of-a-kind alphabetical collection of inaugural issues of comic books from around the world. His feat has been published in this year's Limca Book of Records.
- Art historian pens book on Ramkinkar's troubled final years
The legendary pioneer of modern Indian sculpture, Ramkinkar Baij, spent his last years in a state of depression and creative crisis, due to the rejection of his ideas by the public authorities who commissioned sculptures from him. He was apparently a complete emotional wreck when he died in 1980.