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Health and Fitness Fifth GradeRecords activities on a teacher-designed worksheet. ... endurance; canoeing/kayaking develops muscular endurance. ... Describes function of the endocrine system. Example: http://www.k12.wa.us/HealthFitness/Standards-GLEs/HealthFitnessGLE-Grade5.pdf Preview Maximize
Cross-Curricular Reading Comprehension Worksheets: E-17 of 36 The ...into a muscular bag called the bladder. As you know ... Predict what could happen in your excretory system ... Week 17 reading comprehension worksheet for 5th grade. http://www.k12reader.com/reading-comprehension/Gr5_Wk17_Excretory_System.pdf Preview Maximize
Bony Fish Anatomy WorksheetA properly labeled answer guide is provided for you. Incorporate a fish-making art activity after the worksheet. Suggestions are included after the answer guide. http://www.umma.umaine.edu/downloads/BonyFishAnatomy.pdf Preview Maximize
HUMAN ANATOMY AND PHYSIOLOGY... and physiology of the integumentary system, skeletal system u0026 bones, muscular system u0026 ... ABOUT GRADE REPORTS If you want your grade reports sent to your e-mail address ... http://www.craftonhills.edu/PersonalWebs/bponi/Documents/SYLLABUS FALL02.pdf Preview Maximize
G RA DE L EVEL C ONTENT E XPECTAT IONS... R A D E SCIENCE v.1.09 5 Welcome to Michiganu0027s K-7 Grade ... Atmosphere (2) Earth in Space and Time (ST) Solar System ... digestive, circulatory, respiratory, skeletal, muscular ... http://www.michigan.gov/documents/mde/5-Science_COMPLETE_12-10-07_218320_7.pdf Preview Maximize
Blueprint Grade 5 Science TestBlueprint Grade 5 Science Test for the 2003 Science Standards of Learning The revised ... and sun; and d) historical contributions in understanding the Earth-moon-sun system. http://www.doe.virginia.gov/testing/sol/blueprints/science_blueprints/blueprint_science5.pdf Preview Maximize
THE ENDOCRINE SYSTEM: WHO IS IN CONTROL HERE?Nervous system (Grade 3) 2. Body Systems (Grades 2, 3 ... use colored pencils to complete the worksheet, being sure all colors are different. 5 th Grade, The Endocrine System: Who ... http://www.ckcolorado.org/units/5th_grade/5_TheEndocrineSystem.pdf Preview Maximize
Ontario Life Systems Strand - Grade 5Ontario Life Systems Strand - Grade 5 Human Organ Systems Expectations The Digital ... Describe, using models and simulations, ways in which the skeletal, muscular system and ... http://www.digitalfrog.com/resources/pdf/ont_frog.pdf Preview Maximize
Desert Plants worksheetTitle: Desert Plants worksheet Author: T. Smith Publishing Subject: science worksheet about desert plants Keywords: desert plants; saguaro; palo verde; pincushion ... http://www.tlsbooks.com/desertplants.pdf Preview Maximize
5th Grade Science TestA. digestive and circulatory B. muscular and skeletal C ... Name: Date: Test: Teacher: 5th Grade Science Test Practice Test ... from a different kingdom in the classification system. http://www.dekalb.k12.ga.us/canbylane/files/DEA9112B52CA4920BF4A65659F707533.pdf Preview Maximize
Knowledge and Skills Second GradeKnowledge and Skills Second Grade Standard of Learning 2.1 The student will ... the respiratory system; (helps you use the air you breathe) the muscular system; (all ... http://www.doe.virginia.gov/instruction/health/technical_assistance_guide/grade2.pdf Preview Maximize
Name: P - arts of a PlantName: _____ Parts of a Plant 1. flower The flower makes seeds for the plant. 2. stem The stem supports the plant. http://www.superteacherworksheets.com/science/plant-parts.pdf Preview Maximize
Human BodySystems Project By EvaMcLanahanAssessed QCCStandards: Grade: 9-12 Science Biology 2 Topic: ... List and explain the functions of the organ system . o ... Muscular muscles (skeletal, cardiac, smooth) provides structure; ... http://apps.caes.uga.edu/sbof/main/lessonPlan/HumanBodySysProj.pdf Preview Maximize
5th Grade Science Scope and SequenceMuscular System Present and explain Use skeleton to identify bones Develop Vocabulary Write a ... *Covered in unit B also TC4 WB 199 Graphic Organizer on Exploring Oceans Grade 5 Scope ... http://classroom.jc-schools.net/finchums/5thgradescience.pdf Preview Maximize
HUMAN BIOLOGY... 1990,2000 2 LIFE CYCLE OVERVIEW OF FIFTH GRADE ORGANISMS ... Science Nucleus 1990,2000 3 Students use a worksheet to ... osteology; of joints, arthrology; of the muscular system, ... http://www.msnucleus.org/membership/html/k-6/lc/pdf/lc5hb.PDF Preview Maximize
STUDY GUIDE Teacher EditionThe Study Guide worksheet provides the average to below-average student with an ... Speeding Bone Fracture Recovery..... 81 21-3 The Muscular System ... http://www.mrperrys.net/8thScienceStudyGuideWorksheets.pdf Preview Maximize
The Intimate Side of Plants!Fifth Grade, The Intimate Side of Plants 2001 Colorado ... Background knowledge of classification system. 2. ... Label life cycle diagram on Studying Plants Worksheet #2a ... http://www.ckcolorado.org/units/5th_grade/5_intimatesideofplants.pdf Preview Maximize
Heart DissectionThe heart is an organ of this body system. _____ 2. What is the muscular layer of the heart is called? _____ 3. http://www.morgancc.edu/faculty/smith,l/AnatomyReview/Labs/Heart Dissection.pdf Preview Maximize
FIFTH GRADE PLANT LIFEOVERVIEW OF FIFTH GRADE ORGANISMS WEEK 1. PRE: Identifying animal and plant cell ... On the studentsu0027 worksheet have the students determine whether the organisms http://www.msnucleus.org/membership/html/k-6/lc/pdf/lc5p.pdf Preview Maximize
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Cinema Junkie
San Diego Opera Stages A New Mariachi Opera
- April 22, 2015
Once again San Diego Opera challenges preconceived notions about what opera is and expands the horizons about what it can be with the new mariachi opera "El Pasado Nunca se Termina" that has two performances this Saturday at the Civic Theater.
10th Annual San Diego Student Shakespeare Festival Celebrates The Bard
- April 22, 2015
The San Diego Student Shakespeare Festival returns to Balboa Park this Saturday. If you love the Bard, this free event will remind you why his work remains so vital after more than four centuries.
Behind The Scenes Of 'Cirquetacular! Cirquetacular!'
- April 17, 2015
The Circus Collective of San Diego is a group of circus artists who present original shows that blur the lines between traditional circus and contemporary theatre. Last year they did a film noir circus, "Circustantial Evidence," now they serve up "Cirquetacular! Cirquetacular!"
'Unfriended' Uses Cyberbullying As Catalyst For Teen Revenge Tale
- April 17, 2015
Fifteen percent of high school students experienced cyberbullying last year. The new film "Unfriended" (opening throughout San Diego on April 17) exploits the real life horror of cyberbullying for a teen revenge tale.
Pac-Arts Spring Showcase Kicks Off Fifth Season
- April 16, 2015
Pac-Arts' fifth annual Spring Showcase kicks off Thursday night with the documentary "In Football We Trust."
'Reunion' Screens With Swedish Director Odell In Attendance
- April 10, 2015
There are not a lot of opportunities to meet foreign film directors here in San Diego, so check out Sunday's screening of the Swedish film "Reunion" at the Mingei International Museum with director Anna Odell in attendance.
'The White Snake' Conjures Up Some Magic At The Old Globe
- April 10, 2015
"The White Snake" (continuing through April 26 at the Old Globe Theatre) is an ancient tale about two snake spirits that learn how to transform into beautiful women and live on earth. It provides the perfect foundation for playwright and director Mary Zimmerman, who sees theater as a playground for the imagination.
Once Is More Than Enough For 'Kill Me Three Times'
- April 10, 2015
Simon Pegg is riding a wave of success with roles in the film franchises "Star Trek" and "Mission Impossible." But the new comedy thriller "Kill Me Three Times" (opening April 10 at Landmark's Ken Cinema) won't be adding to his popularity.
Help Bring Death To Life For FX Artist Hiroshi Katagiri
- April 7, 2015
Crowdfunding is a mixed bag. You may feel inundated with people pitching you with projects that you couldn't care less about, but on the other hand it's a blessing for filmmakers working outside the mainstream.
WonderCon Moves To L.A.
- April 6, 2015
WonderCon, the sister convention to Comic-Con, closed its 2015 show in Anaheim on Sunday with the news of change for next year.

subset: commoncrawl


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EAST RUTHERFORD, N.J. — Heels vs. Hoyas. It's a matter of pace.
Today's highly anticipated Elite Eight showdown between Georgetown and North Carolina is likely to come down to tempo.
Roy Williams' 12-deep, transition-happy Tar Heels would be happy to move today's East region final across the parking lot to Meadowland Park. North Carolina (31-6) ranked second in the NCAA in scoring this season (85.8 points) and wants to turn today's game into a sprint.
With its pair of dominating post players, Princeton-based, patient motion offense and superb halfcourt defense, Georgetown (29-6) ranked fourth in the nation in scoring defense (57.0). John Thompson III's Hoyas want a second-gear game in the low 60s.
Something's got to give.
"There's no way we can beat them in a track meet," said 7-foot-2 Georgetown center Roy Hibbert, the player who personifies the Hoyas' strategic identity. "We can't let them establish their up-tempo pace."
One of the primary reasons for North Carolina's fast-paced offense is the play of freshman point guard Ty Lawson. Williams' teams have always played fast, but by his own admission, he has never had a catalyst at the core of his up-tempo offense as diabolically fast as the 5-foot-11 guard from Clinton, Md.
"I think Ty Lawson, before he's finished, has a chance to be the best point guard I've ever coached, and I've coached some really, really good point guards," said Williams, who has tutored the likes of All-Americans Jacque Vaughn and Raymond Felton in his 19 years as the head coach at Kansas and North Carolina. "He's got a gear that not even [Felton] had."
Hibbert knows all about Lawson. The two played AAU ball together for the DC Blue Devils, a team that crushed all comers en route to the AAU national title in 2003.
"I've known Roy for a pretty long time," said Lawson, who averages 10.4 points and 5.6 assists a game. "He was like 6-foot-4 back in fifth grade, when and I was like 4-foot-6."
When Georgetown employs a man-to-man defense against North Carolina, sophomore guard Jessie Sapp likely will draw the chore of checking Lawson.
"Dee Brown at Illinois was quick last year, but we haven't seen anybody like Lawson," Sapp said. "There's nobody in the nation as quick as Ty. As a defender, you've got to play him honest. You can't sit back way off him and give him wide open shots, but you better give him a little space. We know it's going to be a serious challenge."
Georgetown's lack of backcourt depth could be a major factor in defending Lawson and slowing down the North Carolina running game. The Hoyas have only three true guards on the roster in Sapp, Jonathan Wallace and Jeremiah Rivers.


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VIEWS: 51 PAGES: 4 CATEGORY: Lifestyle POSTED ON: 4/6/2010 Attribution-NoDerivatives
Presented by Daniel Toriola Marriage Vows. A convenient, quick, inexpensive tool that helps in easily creating, selecting, personalizing or writing your own meaningful, beautiful wedding vows. A couple's guide to personalizing the most important words you will ever speak. Click here to know more Our Web Hosting Plans Start From Only 41 cents / month. Our Web Hosting Plans Start From Only 41 cents / month. Sorry, We're Only Repeating To Inform That This Isn't A Typo :) Do Check Us Out! Click here to know more Popular Wedding Favors Ideas By Joe Palladino When you are considering different wedding favor ideas it's always a good idea for the couple to shop together. If that is not feasible then research can be done individually, and the two of you can sit down together and compare your thoughts. If you are using some sort of a wedding planner or an organizer, you can jot down your ideas, and sit down and compare notes. Granted with some couples it may be hard to get a man to set down, but he should still be given the opportunity to offer his input. The Internet is an excellent tool when it comes to researching various wedding gift ideas. You can view wedding planning guides, bridal magazines, or google search keywords "wedding ideas" to find various places come up with reception gifts for your wedding guest who have attended your special day. Another thing you can do is talk to friends and family members who've been to weddings and ask what they remember about the favors from the weddings they attended. You are sure to come up with some great ideas from them. Here are 4 ideas, you can keep in mind in how you present the favors you choose. 1. You can get separate and personalize them for your immediate family members and closest friends. 2. For the rest of your guests you can incorporate your own style, or taste into the gifts that you hand out. 3. When coming up with various choices, it's important that you choose your gifts based around the theme of the wedding your planning. It will be easier to express your joy and thankfulness for them attending your special event. 4. Do not feel frustrated or rushed if you're running out of time and your wedding day is quickly approaching. Here are four popular wedding favor ideas that have been used in the past. Wedding Themes And More An excellent source of unique wedding books and wedding theme ideas. Page 1 Presented by Daniel Toriola 1. Colorful flowers such as roses. Your optimism that you have for your life together can be expressed when you use vibrant, fresh, flowers. 2. Photo packs.These are great as you can customize them around the wedding and reception as it is happening. 3. Gift baskets full of chocolate or cookies. These are a safe bet as everyone likes cookies or chocolate. 4. Your guests already know someone has won the key to your heart. Show them that you care about them as well. The heart shaped metal Keychain Key to Love in Deluxe Box sports a tag made of resin which proclaims that you have found the key to love. The Keychain Key to Love in Deluxe Box measures 5" x 1.75" inches and is tied with a striking white organza bow, to which is attached a matching heart shaped thank you card. The display box and gift combination makes a lovely place setting decoration and sets off the theme of the Key to Love. Regardless of which you choose, try and get this decision prepared and finalized early. This will free up more time for other details pertaining to your wedding day. This should give you a few great wedding reception gift ideas and help you pick them out. Joe Palladino invites you to visit his wedding favors ideas website for all of your shopping needs. They offer beach wedding favors, bridal shower wedding favors, and daily favor specials. With over 3000 items to choose from be sure and check out their best price guarantee. You can do that here now: ----> http://www.herweddingfavors.com Wedding Planner Tips Wedding Planning Guide - expert planning tips, timelines, worksheets, money-saving techniques, fresh ideas and much more. Page 2 Presented by Daniel Toriola Wedding Favors Everyone Will Love By George Meszaros It is common practice that the bride and groom will offer a small token of appreciation to their wedding reception guests, commonly known as wedding favors. There are many different kind of wedding favors. Wedding favors vary in material and purpose. The savviest brides often seamlessly integrate the wedding favors into their wedding theme. For example, a beach wedding may have beach wedding favors, such as flip-flop candles as wedding favors. A common characteristic of wedding favors is that they are usually inexpensive. Brides and grooms usually spend no more than a few dollars per guest. Many brides chose to make their own wedding favors, but most will end up purchasing them ready made. It is important to remember that the primary purpose of the wedding favor is to show your appreciation toward your wedding reception guests, your friends and your family. The most popular wedding favors are edible. The most popular edible wedding favors are chocolate. Personalized chocolates are especially popular with brides and wedding guests. Let's face it, everybody loves chocolate, so chocolate wedding favors are a sure hit with wedding guests of all age. While some wedding favors may be more popular with women than man, or vice versa, chocolate is a gender-neutral wedding favor. To make chocolate wedding favors even more exiting, some companies offer personalized chocolate wedding favors. Personalization adds a special touch of elegance to your wedding favors. The personalization service includes printing the names of the bride and groom on the front of the candy wrapper. Some companies even offer to print a special message from the bride and groom on the back of the wrapper. Not only, that the personalized chocolate wedding favors can include the names of the bride and groom, but they can be color coordinated to fit the wedding colors. George Meszaros is affiliated with Sweet Reflections; a leading provider of wedding favors http://www.sweet-reflections.com Wedding Speeches & Wedding Toasts Pre-written wedding speeches & toasts for the best man, maid of honor and father of the bride. HIGH CONVERSION. 50% payout. Page 3 Presented by Daniel Toriola Related eBooks: Wedding Favors Everyone Will Love Wedding Favors: Important Things You Need To Know Deciding On Your Wedding Favors Every Bride Must Have It Wedding Favor Selection Process Get more Free PDF eBooks at FreePDFeBooks.com Related Products: Wonderful Wedding Favors and Wedding Gifts Bread And Biscuit Baker's And Sugar-Boiler's Assistant Start your Own Wedding Videography Business The Art of Kissing 147 Killer Epublishing Strategies Malamaal.com: A genuine resource center for Quality Ebooks and Softwares This PDF eBook is for free Distribution only, it cannot be SOLD Diamond Ring Secrets The secrets of buying a diamond engagement ring without being ripped off. Click here to know more Powered By FreePDFeBooks.com ReBrand this PDF eBook with your Name / URL / ClickBank Affiliate ID for Free Brainstorm: Get Easy, Quick Ideas! Discover How To Explode Ideas for business, inventing or creativity. A complete Ideas Creation System that works: try it now. Page 4
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Dr. Barbara Wismer is a family doctor in San Francisco, CA, delivering primary care services for all members of the family – from kids to seniors.
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The Mask Bar, Cocktail Bar
Choose from a multitude of delicious cocktails in the sophisticated ambience of the Mask Bar. Be it drinks before a show or a nightcap to end a great evening, the Mask Bar is the ultimate venue to unwind and relax. For booking queries, please contact our Food & Beverage Department: email@example.com.
Celebrate World Gin Day on 13 June 2015 with our fruity cocktail 'Berry Bliss'. Combining summer berries and Brockman's Gin, the cocktail is perfect for after work or pre-theatre drinks. Why not have a go making your own version, see our recipe below:
Berry Bliss
- 37.5ml Brockman's gin
- 12.5ml Crème de Cassis Dash
- Blackcurrant cordial Cranberry juice
- Squeeze of lime
- Few drops of Tabasco
- 4 blueberries
- 2 raspberries
- Muddle and shake Rocks glass crushed ice
- Garnish: 1 raspberry, 1 blueberry, ½ strawberry on cocktail stick
Add a little gin to your stay at the Gin Palace' for only £8.50* choice from quench-thirsting selection of cocktails: Mask Negroni, Raspberry Collins, Black Forest Martini, Gin & Grapefruit.
*This offer is available until 30 September and applies to adults aged 18 years and over
View the Mask Bar's Cocktail Menu
Monday –Saturday 5.00pm till 3.00am
Sunday: Closed


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In This Section
Journal Forum
Clean Audio for TV broadcast: An Object-Based Approach for Hearing-Impaired Viewers - April 2015
2 comments
Audibility of a CD-Standard A/DA/A Loop Inserted into High-Resolution Audio Playback - September 2007
13 comments
Sound Board: Food for Thought, Aesthetics in Orchestra Recording - April 2015
2 comments
AES Convention Papers Forum
Investigation of Crosstalk in Self Oscillating Switch Mode Audio Power Amplifier
Self oscillating switch mode power amplifiers are known to be susceptible to interchannel disturbances also known as crosstalk. This phenomenon has a significant impact on the performance of an amplifier of this type. The goal of this paper is to investigate the presence and origins of crosstalk in a two channel self oscillating switch mode power amplifier (class D). A step by step reduction of elements in an amplifier built for this task, is used for methodically determining the actual presence and origins of crosstalk. The investigation shows that the crosstalk is caused by couplings in the self oscillating pulse width modulation circuits, but also that the output filter has a major impact on the level of crosstalk.
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Building Rapport with NLP In A Day For DummiesBecome an effective communicator and create rapport with ease Building Rapport with NLP In a Day provides you with all the tools you need to make and break rapport and communicate effectively. Designed to contain a day's reading, this handy guide explains how Neuro-linguistic Programming (NLP) skills can help you to use the power of your senses to see, hear and feel your way to better
Personal Development All-In-One For DummiesA complete guide to understanding how you think, and discovering how to think differently. Personal Development All-in-One For Dummies is a complete guide to the key techniques that help you master your thoughts: Neuro-linguistic Programming (NLP), Cognitive Behavioural Therapy (CBT), Life Coaching and Hypnotherapy. Discover the basic principles of each approach and receive sensible, practical and
Neuro-Linguistic Programming Workbook For DummiesIf you are one of the millions of people who have already discovered the power of NLP, Neuro-linguistic Programming Workbook For Dummies will allow you to perfect its lessons on how to think more positively and communicate more effectively with others. This workbook is packed with hands-on exercises and practical techniques to help you make the most of NLP's toolkit for new thinking and personal
Neuro-linguistic Programming For DummiesLearn how to apply NLP to fine-tune life skills, build rapport, enhance communication, and become more persuasive One of the most exciting psychological techniques in use today, neuro-linguistic programming helps you model yourself on those-or, more accurately, the thought processes of those-who are stellar in their fields. Rooted in behavioral psychology of the 1970s, the concepts of NLP are now
Neuro-linguistic Programming for DummiesNLP has a simple premise: take someone who's good at something, model how they do it and learn from them. This way it is possible to understand the thought processes common to excellence in any field and weed out negative or habitual thinking. Neuro-Linguistic Programming techniques extremely popular in many areas including business, education, sports, coaching, counselling, personal development
Instant Manager: Overcoming Information OverloadAs a manager and leader are you faced each day with an avalanche of new and bewildering demands? Do the days seem to get shorter as you try to juggle a demanding career with developing new skills and maintaining a balanced life? Relax! Instant Manager is a new way of winning back time and growing your confidence and professionalism with the support and guidance of THE experts in management. Based
$14.99The Coaching Bible is a practical and inspiring book from the UK's top coaches Ian McDermott and Wendy Jago, authors of The NLP Coach and Your Inner Coach. Coaching has become an integral part of our lives, but people still need to know how to make the most of what coaching can offer. The Coaching Bible is the only book on coaching that you need. It offers unique, valuable and expert advice to
Manage Yourself, Manage Your Life
Vital NLP Technique For Personal Well-Being and Professional SuccessAre you getting what you want out of life? Do you dream of a more rewarding career? Would you like a happier, more fulfilling relationship? MANAGE YOURSELF, MANAGE YOUR LIFE is your essential guide for living in the twenty-first century. Based on powerful NLP (neuro-linguistic programming) techniques, this practical handbook will help you create the new life that you deserve. You will discover how
$13.99Created especially for the Australian customer!Release your potential and get better exam results with this essential guideDo you panic at the thought of exams? Do you think you're just not the academic type? No matter how old you are, exams can be stressful -- but they don't need to be. This essential guide provides expert tips on how to change your mindset, improve how you learn and revise,
How to Achieve Results from Crucial ConversationsHow to handle difficult discussions in the workplace Packed with practical and pragmatic suggestions and methods for dealing with the tough stuff at work, this unique and helpful book features simple diagnostics, models, and processes that you can put to use immediately. The author team shares their years of research and experience so that you can benefit from their case studies and examples, all
The ultimate guide to presenting your ideas and influencing people using techniques that actually workDo you get nervous when presenting at work? Do you want to showcase your knowledge, influence people and accelerate your career? Would you like to learn the secrets of successful speaking, communicating and presenting? How to Present reveals how you can be a confident, clear and influential presenter every time. Presentation skills expert Michelle Bowden shares her internationally proven 13-step
$11.19Writing a journal helps you to understand the past, deal withthe present and look forward to the future.This book conjoins Therapeutic Journaling, Cognitive Behaviour Therapy, and Rational Emotive Behaviour Therapy. These talking therapies have been used to form the basis for writing templates to help you to address your specific situation. The extraordinary value of this book is that you can bend


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Food - Page 17
Woman Catches Car Thief in Her Drive Thru
Nothing worse than your car getting stolen, but I am sure there is nothing more satisfying than catching the thief yourself.
61 Year Old Borrows Parents' Car and Robs a Subway
If your 61 year old son came to you and asked to borrow your car, you would think he would be responsible with it.
Kids Eating New Food in Slow Motion [VIDEO]
As Dave Chappelle once said "Not everything is good in slow motion", but this is funny though.
If You Post the Food You Eat on Instagram, You May Have an Eating Disorder
If you get on social media around dinner you see it. Someone posting the food they eat and it is starting to get annoying. According to a doctor you may have a problem.
Would You Want to Watch Your Pizza Being Made on a Live Webcam?
Domino's is trying something new and I think it is really weird.
Have You Been Eating Apples the 'Wrong' Way? [VIDEO]
Apples are not only tasty, they're good for you. When you eat an apple, however, you might be doing it the wrong way. The old tradition of just biting in and leaving the core has gone by the way side, as this video shows you how to eat an apple like a boss
Kid Falls Asleep While Eating Chicken Nuggets [VIDEO]
Prepare for the longest last bite in the history of food.
Twinkies Are Officially Coming Back in July
To all my fellow junk food junkies do not have a heart attack we still have to wait 3 months.
How Much Food Can You Buy With $5?
How much food could you buy with just $5? Well here in the states that might buy you a hamburger and some fries or maybe eight and a half pounds of bananas. But what if you took that same exact $5 to Ethiopia? Would you be surprised to learn that you could buy 25 pounds of bananas for the same price?
I found this video on Youtube and it's pretty cool to see how far, or not so far $5 can get you in different countries
How To Make a Mexican Bulldog Margarita
The Mexican Bulldog is different because it contains a bottle of Corona, which sits upside-down in the glass.
New Milk That Will Taste Like the Bottom of the Cereal Bowl [VIDEO]
If you are like me the best part of the cereal is the delicious milk that is left afterwards. Well a company is finally making a drink that will attempt to taste like some of your favorite cereals.


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A radial arm saw features light weight, portability and simplicity of construction. A standard supports a one-piece radial arm that comprises a pair of horizontal, vertically spaced cantilever rails rigidly joined at their outer ends by an integral connecting member. A sliding runner spans the rails and has vertically spaced bearing parts receiving corresponding rails. A vertical spindle on the runner is connected at its lower end to the top of a cage that receives a conventional portable circular saw, thereby suspending the saw unit beneath the rails and above the work surface. The spindle permits the cage to be rotated for either cross-cut or ripping operations, and the radial arm is adjustable in a horizontal plane by a special detent arrangement on the standard that allows the elevation of the saw unit to be varied in any selected radial position.
1. Radial arm saw apparatus comprising: a work-supporting surface;
an upright support adjacent said surface;
a pair of vertically spaced, upper and lower cantilever rails fixed to said support, extending generally horizontally therefrom above said surface, and each presenting an outer end remote from said support,
said rails lying in a common vertical plane;
a connecting member spanning the outer ends of said rails, rigidly joined to said ends and maintaining the same fixed relative to each other;
a power-driven saw unit;
a carrier beneath said lower rail receiving said unit and mounting the same in an operational position; and
means on said rails movable therealong and suspending said carrier therebeneath, whereby the carrier and hence the saw unit can be advanced along a path defined by said rails to make a cut in a workpiece positioned on said surface.
2. The apparatus as claimed in claim 1, wherein the outer ends of said rails are in substantial vertical alignment, and wherein said connecting member lies in said plane.
3. The apparatus as claimed in claim 1, wherein said rails and connecting member present a radial arm of onepiece, unitary construction.
4. The apparatus as claimed in claim 3, wherein the outer ends of said rails are in substantial vertical alignment, and wherein said connecting member lies in said plane.
5. The apparatus as claimed in claim 4, wherein said rails are in parallelism, and wherein said connecting member is elongated and longitudinally arcuate and extends outwardly beyond said outer ends.
6. The apparatus as claimed in claim 1, wherein said rails are in parallelism, and wherein said movable means includes a runner spanning said rails and having vertically spaced, upper and lower bearing parts receiving corresponding rails for sliding movement of the runner therealong.
7. The apparatus as claimed in claim 6, wherein said runner has structure between the rails rigidly supporting said bearing parts in spaced relationship aligned with corresponding rails.
8. The apparatus as claimed in claim 6, wherein said movable means further includes a vertical spindle on said runner having a lower end secured to said carrier to suspend the latter beneath the rails, said spindle establishing a vertical axis for rotation of said carrier about said axis to a selected position for crosscut or ripping operations, and means releasably locking the carrier to the runner in the selected position.
9. The appartus as claimed in claim 8, wherein said saw unit has a rotary blade, and wherein said carrier comprises a cage circumscribing said unit and having a bottom supporting the unit with said blade projecting below said bottom toward said surface, and a top to which said lower end of the spindle is secured.
10. The apparatus as claimed in claim 1, wherein said saw unit has a baseplate and a rotary blade projecting through said baseplate, and wherein said carrier comprises a cage circumscribing said unit and having a bottom receiving said baseplate thereupon and a top secured to said movable means, and means releasably locking said baseplate to said bottom.
11. The apparatus as claimed in claim 10, wherein said cage has a side member provided with a handle to facilitate advancement of the cage in making a cut.
12. The apparatus as claimed in claim 1, wherein said support includes a standard and a tubular component telescoped thereon, said rails having inner ends secured to said component, said standard presenting a vertical axis and having vertically extending slots therein angularly spaced with respect to said axis, said component being provided with detent means selectively receivable in individual slots upon rotation of said component about said axis to permit the rails to be releasably held in a selected angular position in a horizontal plane, and wherein is provided means for raising and lowering said component on said standard whereby, over a range permitted by said slots, the elevation of the saw unit may be varied with said detent means engaged.
13. The apparatus as claimed in claim 1, wherein said support includes a standard and a coaxial, tubular component telescoped thereon having a closed upper end, said rails having inner ends secured to said component, and wherein is provided screw means extending axially of said standard and component and threaded through said upper end of the component for raising and lowering the latter on said standard to vary the elevation of the saw unit.
This invention relates to a radial arm saw which is portable and relatively uncomplex mechanically without sacrificing versatility of operation and the ruggedness required of saws of this type.
The radial arm saw is a standard shop tool that is useful in a wide variety of applications, but it is not inherently portable nor inexpensive. Though desirable, commercially available saws of this type have a cost beyond the reach of many hobbyists and do-it-yourself enthusiasts. Much of the mechanical complexity is in the construction of the radial arm and the reciprocal carriage that contains the cutting blade and drive. Furthermore, the inherent weight normally associated with conventional radial arm saws is due to the radial arm construction and the amount that it requires.
It is, therefore, the primary object of the present invention to provide a radial arm saw which overcomes the disadvantages heretofore considered inherent in saws of this type, and to thereby provide a saw of simplified construction which renders the saw apparatus lightweight and portable.
As a corollary to the foregoing object, it is an important aim of this invention to provide a saw as aforesaid which overcomes the mentioned disadvantages without sacrificing versatility of operation or structural strength of the components of the mechanism.
Still another important object of the invention is to provide a saw as aforesaid wherein the construction of the radial arm is materially simplified and a substantial weight reduction is realized, thereby contributing significantly to the portability of the overall assembly and a reduction in its cost.
Yet another important object of the invention is to provide a saw as aforesaid wherein the radial arm is of one-piece construction and presents a pair of horizontally extending, cantilever rails spaced apart in a vertical plane, the outer ends of the rails being spanned by an integral connecting member that maintains the ends fixed relative to each other.
Additionally, it is an important object of the invention to provide a means of suspending the cutting unit beneath the aforesaid rails, wherein such means employs a runner spanning the rails and having bearing parts receiving corresponding rails for sliding movement of the runner therealong, the bearing parts being rigidly supported in vertically spaced relationship so that the weight of the suspended cutting unit is supported by both rails held in a fixed spaced relationship.
Furthermore, it is an important object of the invention to provide a special mount for the suspended cutting unit, in the form of a cage particularly adapted to receive a conventional portable circular saw utilized as the power driven cutting unit.
Other important objectives are to provide selectivity as to crosscut or ripping operations, adjustability of the angular position of the radial arm in a horizontal plane, and a simple height control for varying the elevation of the radial arm and hence the elevation of the cutting unit with respect to the work surface.
In the drawings:
FIG. 1 is a side elevational view of the saw apparatus of the present invention, movement of the power driven saw unit and its supporting cage along the radial arm being indicated by the broken line illustration;
FIG. 2 is a fragmentary, end view of the apparatus shown in FIG. 1, the ripping position being indicated in broken lines;
FIG. 3 is a side elevational view of the runner, cage and saw unit from the side opposite that seen in FIG. 1;
FIG. 4 is an enlarged, fragmentary, vertical sectional view taken along line 4--4 of FIG. 1;
FIG. 5 is a cross-sectional view taken along line 5--5 of FIG. 4, the detent being shown in plan for clarity;
FIG. 6 is a view of the runner casting from which the cage is suspended, showing the same partially in plan and partially in horizontal section and on the same scale as FIGS. 4 and 5;
FIG. 7 is a vertical sectional view taken along line 7--7 of FIG. 1 and on the same scale as FIGS. 4-6, the spindle and certain other components being shown in elevation for clarity;
FIG. 8 is a detail view of the releasable saw lock;
FIG. 9 is an enlarged, fragmentary, cross-sectional view taken along line 9--9 of FIG. 3; and
FIG. 10 is a fragmentary, cross-sectional view along line 10--10 of FIG. 9.
Referring initially to FIG. 1, the saw apparatus includes a tubular standard or post 20 which supports a radial arm broadly denoted 22. A relatively short tubular component 24 having a closed upper end 26 is telescoped over the upper portion of the standard 20 and is formed with a pair of upper and lower bosses 28 and 30 respectively. The radial arm 22 is of one-piece construction and, as viewed in FIG. 1, has an appearance resembling the slide of a slide trombone. The arm 22 may be formed from cold rolled steel, either solid or tubular stock.
By virtue of its configuration and construction, the arm 22 presents a pair of upper and lower cantilever rails 32 and 34 respectively which extend horizontally in parallelism from the standard 20. As may be appreciated from a comparison of FIGS. 1 and 2, the rails 32 and 34 lie in a common vertical plane as does the integral connecting member 36 that spans the outer ends 38 and 40 of the rails 32 and 34 respectively. The member 36 is longitudinally arcuate and extends outwardly beyond the rail ends 38 and 40. Representative spacing between the parallel rails 32 and 34 would be approximately three inches (7.6 cm.) for a total arm length of 24 inches (61 cm.).
Referring to FIGS. 1, 4 and 5, it may be seen that the inner ends 42 and 44 of the respective rails 32 and 34 are externally threaded and secured to the tubular component 24 at the bosses 28 and 30. The bosses extend horizontally and are bored to receive the ends 42 and 44, which are then firmly secured by pairs of nuts 46 and 48 on the respective ends 42 and 44 engaging opposite ends of the horizontal bosses 28 and 30. The component 24 is coaxial with the standard 20 but is prevented from rotating thereon by a detent 50 which is biased by a spring 52 into any one of three vertical slots 54 in the standard 20. The slots 54 are angularly spaced about the vertical axis of the standard 20, the center slot 54 establishing the normal position of the radial arm 22 for regular crosscut operations (as shown). An integral knob 56 on the detent 50 permits the same to be manually shifted against the bias of the spring 52 so that the arm 22 may be swung in a horizontal plane to a 45� position either left or right of center established by the two outer slots 54. Intermediate positions may also be selected by withdrawing the detent 50 and locking the component 24 to the standard 20 through the use of a set screw 58 provided for this purpose.
Variation of the elevation of the radial arm 22 is accomplished by a vertical screw 60 threaded through the upper end 26 of the component 24 in coaxial relationship with such component and the standard 20. A crank handle 62 (FIG. 1) on the upper end of the screw 60 permits the operator to readily rotate the screw in either direction to raise or lower the component 24 on the standard 20. As may be seen in FIG. 4, this is accomplished by the lower end of the screw 60 in that it bears against a center recess in a disc 64 overlying the upper end of the standard 20. A small screw 66 is loosely received in a central opening through the disc 64 and is threaded into the lower end of the elevating screw 60 in order to serve as a retainer to prevent separation of the disc 64 from the screw 60 (and possible loss of the disc 64) upon disassembly of the standard 20 and component 24.
Now referring particularly to FIGS. 1-3, 6 and 7, the cutting assembly of the present invention includes a runner 68 which rides on the rails 32 and 34 and suspends a carrier 70 therebeneath, such carrier being in the nature of a cage that serves as a mount for a conventional portable circular saw unit 72. The runner 68 is a casting of vertically elongated configuration that spans the rails 32 and 34 and is provided with upper and lower sleeve bearings 74 and 76 respectively receiving corresponding rails 32 and 34. A lug 78 projects laterally from the top of the runner 68 and a flange 80 likewise projects from the bottom thereof, the lug and flange being bored to receive a vertical spindle 82 which is welded to the top 84 of the cage 70 at its lower end. A locking pin 86 extends through any one of three holes 88, 90 and 92 in the flange 80 and is received by an opening 94 in the cage top 84. The holes 88, 90 and 92 are spaced apart at angular intervals of 45� about the axis of the spindle 82, the hole 90 when aligned with the opening 94 (as illustrated) defining the position of the cage 70 for crosscut operations. The locking pin 86 may be removed and the cage 70 rotated until the opening 94 is aligned with either hole 88 and 92 and the locking pin reinserted, either of these latter positions being used for ripping. The broken line illustration in FIG. 2 corresponds to alignment of hole 88 with opening 94 which places the handle 96 on the right side as viewed in FIG. 2. A set screw 97 is threaded into the upper sleeve bearing 74 and is used to hold the runner 68 stationary on the radial arm 22 during ripping operations.
The top 84 of the cage 70 is held in flush engagement with the horizontal bottom surface presented by the flange 80 by a coil spring 98 telescoped over the upper end portion of the spindle 82. The spring 98 is loaded in compression between the lug 78 and a pair of nuts 100 threaded on the upper end of the spindle 82.
The cage 70 as illustrated is made from a strip of metal plate stock formed into a closed, generally rectangular frame configuration. The ends of the strip join at the lower righthand corner of the cage 70 as viewed in FIG. 1, and are welded at that point. The top 84 is flat, as is the bottom 102, and both extend horizontally in parallelism except for the three rounded corners. Likewise, the opposed side members 104 and 106 are disposed in parallelism but at right angles to the top 84 and bottom 102, the handle 96 being secured to the member 106. It may be appreciated that the cage 70 circumscribes the saw unit 72 with its bottom 102 serving as a mounting base for the unit as will now be described in detail.
The saw unit 72 has a frame consisting of a motor housing 108, a fixed blade guard 110 and a handle 112 as basic components. A rotary blade 114 is attached to the driven shaft 116 of the motor drive, the electric motor itself and the gear drive to the shaft 116 not being illustrated herein in detail. The particular unit 72 shown is a model 574, 71/4 inch power saw manufactured by Skil Corporation of Chicago, Ill., and sold under the trademark SKILSAW. The unit 72 has a baseplate 118 of rectangular configuration which presents a pair of opposed end edges 120 and 122. The baseplate 118 directly overlies the bottom 102 of the cage 70, with the edge 120 being inserted under a pair of screws 124 in the side member 106 which project into the cage 70. The opposite edge 122 (see FIG. 8) is captured beneath a locking catch 126 which is biased toward the locked position illustrated by a coil spring 128. A knob 130 on the outer end of the stem of the catch 126 provides a convenient means whereby the catch may be withdrawn against the bias of the spring 128 to disengage the inner end of the catch 126 from the edge 122, thereby releasing the saw unit 72 from the cage mount. The unit 72 is further stabilized by a pair of upstanding pins 132 on the cage bottom 102 which are received within openings in the baseplate 118. In the particular unit illustrated, such openings in baseplate 118 exist in the unit as manufactured and thus are employed in the present invention in conjunction with the appropriately positioned pins 132. It will be appreciated that other circular saw units may also be employed and, in that case, the pins 132 would be relocated as necessary. A counterspring 134 is attached to a stud 136 on the movable blade guard of the unit 72 to maintain the movable guard in a raised position (hidden from view in FIG. 1) where it does not interfere with the portion of the blade 114 projecting below the baseplate 118.
Circular saws such as illustrated at 72 provide for vertical adjustability of the rotary blade 114 as may be seen in FIG. 3. This adjustment is accomplished by loosening the wing nut 140 on the handle 112 to permit the frame of the saw unit to pivot about the axis of a hinge pin 142. Similarly, tilting of the saw blade 114 relative to the plane of the baseplate 118 is accomplished by loosening a wing nut 144 so that the frame of the unit can pivot about a horizontal axis provided in the unit which extends in parallelism with the baseplate 118 longitudinally thereof (parallel to the radial arm 22 when the cage 70 is in the crosscut position illustrated in FIGS. 1 and 3 and in FIG. 2 in full lines).
The electric motor within the housing 108 is activated by a trigger 146 which, when depressed, closes an internal electric switch (not shown). For the convenience of the operator since handle 96, not the handle 112 of the saw unit 72, is used in the operation of the saw apparatus of the present invention, means is provided to hold the trigger depressed to maintain the motor energized. This is illustrated in FIGS. 9 and 10 where it may be seen that a U-shaped clasp 148 holds a plate 150 against one side of the handle 112 adjacent the trigger 146, the plate 150 serving as a mount for a rotatable crank 152. The shaft of the crank 152 extends through the plate 150 and into the hollow of the handle 112 where the trigger 146 is located, the inner end of such shaft being provided with an eccentric cam 154 which engages the trigger 146 and depresses the same when the crank 152 is rotated to the broken line position thereof illustrated in FIGS. 3 and 10. Due to the interference between the cam 154 and the trigger 146 created by the internal return spring (not shown) of the trigger 146, the cam 154 remains in the actuated position to hold the trigger depressed until the crank 152 is returned by the operator to the position illustrated in full lines.
In FIG. 1 it may be seen that a table base structure for the saw apparatus comprises an angle iron frame 156 to which the lower end of the standard 20 is welded at the center of the inner frame member 158. The frame 156 is preferably square and holds two square pieces of particle board 160 stacked one on top of the other within the frame 156. Each piece of particle board 160 may be turned 90� four times and inverted; accordingly, 16 surfaces are effectively provided to compensate for wear in normal use. A stop block 162 is secured to the work surface by any suitable means adjacent the base of the standard 20 and extends along the inner margin of the surface to provide a guide for the work piece (not shown).
In the utilization of the present invention, it is evident that the saw apparatus may be disassembled into its major components for convenient portability, or transported as an assembled unit. At such time, the circular saw 72 would normally be removed from the cage 70 for conventional use as a portable hand saw. It may be appreciated that the circular saw is very quickly returned to the cage 70 by withdrawing the locking catch 126, placing the baseplate 118 on the cage bottom 102 in proper position on the pins 132 with the end edge 120 inserted beneath the retaining projections provided by the screws 124, and then releasing the catch 126 to engage the same with the end edge 122 and lock the baseplate 118 to the bottom 102.
The work piece is placed on the supporting surface provided by the stacked pieces of particle board 160 against the stop block 162 and cutting operations proceed in the usual manner for saws of the radial arm type. For crosscut operation, which is the mode illustrated in FIG. 1, the operator grasps the handle 96 on the cage 70 and advances the blade 114 as desired along the path defined by the rails 32 and 34. The angular position of the radial arm 22 (rails 32 and 34) in a horizontal plane is quickly and conveniently set by withdrawing the knob 56 of the detent 50 and rotating the arm to the desired position. At 45� left or right of center, the detent 50 snaps into the respective outer slot 54 (FIGS. 4 and 5); the set screw 58 is employed for other angles.
At the primary angular positions defined by the three slots 54, the radial arm 22 remains locked in place during height adjustments. This feature is provided by the vertical elongation of the slots 54 in cooperation with the detent 50 which rides in the respective slot as the screw 60 is rotated in either direction by the crank handle 62. The slots 54, therefore, define a wide range of elevation adjustment to facilitate different diameters of the saw blade 114 or different saw units 72 that might be employed.
For ripping operations, as mentioned above, the spindle 82 permits rotation of the cage 70 as illustrated in broken lines in FIG. 2. The locking pin 86 is momentarily removed from the hole 90 and reinserted through either hole 88 or 92 and the underlying opening 94 in the cage top 84. The set screw 97 holds the runner 68 and cage 70 at the desired position along radial arm 22, and the work piece is advanced through the blade 114.
It should be particularly noted that the radial arm 22, although cantilever supported and of lightweight construction, remains stable and does not bend or deflect when the cage 70 is adjacent its outboard end as illustrated in full lines in FIG. 1. The stability imparted is due to several factors including the one-piece construction of the radial arm and the location of the spaced rails 32 and 34 in a common vertical plane. The connecting member 36, being integral with the rails 32 and 34, is rigidly joined to the outer ends 38 and 40 of the rails and maintains such ends fixed relative to each other. This further contributes to the stability of the radial arm since the vertical spacing of the rails 32 and 34 is fixed at both the inner and outer ends; accordingly, for the upper rail 32 to be placed in tension, the lower rail 34 must be placed in compression and the rails thus resist any tendency to bend or deflect. Additionally, the upper and lower sleeve bearings 74 and 76 on the runner 68 are rigidly supported by the runner casting in fixed spaced relationship aligned with and receiving the corresponding rails. This maintains the rail spacing at the runner 68 at intermediate positions thereof along the length of the radial arm as illustrated, for example, by broken lines in FIG. 1.
Patent Citations
Referenced by
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text:
Absolute worst character in DS9 History: Ezri Dax
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September 19 2013, 02:18 PM
Re: Absolute worst character in DS9 History: Ezri Dax
R. Star wrote:
KaraBear wrote:
IzzyatWarp9 wrote:
Ermegherd treason
I know everybody loves her but she irritated me. She was so good at everything, they guys all lusted after her, blech
I always thought Jadzia was overrated too. Terry Farrel is definitely cute, but the character's personality was just so... random. There were like three different versions of her and none of them merged together well. The aloof smart person who can figure out anything, the party girl who gets drunk and plays tongo with Quark, and the avenging valkyrie who fights with and hangs out with Klingons.
And chalking that off to the symbiont is just a cop out. Jadzia herself said in Playing God when she was training that Trill Initiate that while the symbiont influences them, the host is supposed to be disciplined enough to define themselves over it.
Did we agree on something?
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text:
MF Podcast Review: 2006 BMW 325i
The BMW 3 series is a design, engineering and performance icon. One of the few cars that are on par with the Mini's similarly long history. An engine mounted behind the front wheels gives the car a perfect 50/50 weight distrubtion and a composure at the limit unheard of in most consumer sedans. All this makes for an automobile that is as at home on the track, as it is around town.
Beyond the obvious reasons to take a 325i out for a drive, the next MINI will also share quite a few components in and outside of the car. So with the 2007 MINI just six months away from initial production, it seemed like a good time to get aqauinted with some of this new technology. Now it's worth noting that I've spent a good amount of time in various versions of the new 3 series. And as it would happen the particular car that I used for the audio review was the most plainly specced one I've driven. No manual and no sport package meant the car wasn't quite the thrill that some 3 series (including the one in my garage) can be. But that aside it's a quick preview of a few new key technologies we'll see next year.
[ BMW 325i Podcast Review
An official photos BMW 325i, identical to car test but with Sport Package:
3 series interior sans navigation. The radio interface in the next generation MINI will be vaguely similar to what is show below:
Notice the almost complete lack of front overhang. BMW mounted the inline six behind the front wheels for perfect distrubution of weight. It hurts packaging but helps make the car the benchmark of performance that it is:
The actual car tested (without sport package):
The BMW 330i with the sport pack (the one to drive if you can):
Written By: Gabe
Pingback: whiteroofradio.com » Woofcast #42()
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follow Dictionary.com
Blair never made the mistake of underestimating Brooks, and his own considerable powers of ingratiation were exercised on her.
1620s, possibly via 16c. Italian ingraziarsi "to bring (oneself) into favor," from Latin in gratiam "for the favor of," from in "in" (see in- (2)) + gratia "favor, grace" (see grace).


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If your fitness goals include reducing body fat, high-intensity workouts that feature whole-body movements have been proven to be effective. Check out this mini-circuit workout, which can help you burn tons of calories while building up your strength and endurance as well.
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Female , 13-15
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Hi, I'm Victoria and I'm a Tumblr Addict and I like the smell of old books.
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I feel extremely self-absorbed sometimes. Although I don't talk about me a lot, when I talk to people, we're usually talking about something I want to. I don't know how it happens..it just does. I don... [more]
Beautiful Mistakes Night times were always the worst for her, which was okay for everyone else because they didn't see the horrors she faced. Her parents slept calmly without wake while she faced her darkest demons. Her… [more]
My Story Of Heart Break Um, my story is a little different..some would call it crazy but it happened.. March 18, 2012 I had gotten a text from a number I didn't recognize. It said "Hey Lisa (:". My … [more]
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At 12 The detentions of fate shatter Break into small, irreparable pieces Look into the mirror, see nothing Everyday the insanity increases Severed shreds of crushed hearts … [more]


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July 9, 2015 from 7pm to 9pm
July 11, 2015 from 12pm to 2pm
July 16, 2015 from 6pm to 9pm
May 6, 2015 at 6am to August 12, 2015 at 11:45pm – CityArts Factory I want every board out there to be submitted to this event. Wake boards, Surfboards, Long Boards, Paddle boards, Snow Boards etc Recreational boards only Boards: converted or have accessories I wil… Organized by Tr3 | Type: group, exhibition
June 16, 2015 at 11am to July 11, 2015 at 11am – CityArts Factory Call for Artists Exhibition Title: "Stars and Stripes" Dates: July 16, 2015 – August 14, 2015 Artist Opening Reception: Third Thursday July 16, 2015 from 6:00 pm – 9:00 pm Subject Matter: "Stars a… Organized by Slice Administrator | Type: art
June 25, 2015 at 6pm to September 18, 2015 at 11:45pm – The Polasek Museum Application Deadline: Friday, September 18, 2015 The Albin Polasek Museum & Sculpture Gardens is now accepting submissions for the 2015-2016 Exhibition "Sight Unseen: Touchable Sculpture" Sight U… Organized by Polasek Museum | Type: call, for, artists
June 25, 2015 at 6pm to July 10, 2015 at 5pm – Downtown Orlando The City of Orlando has produced the popular Historic Preservation Board Calendar since 1989 and each is an exceptional depiction of Orlando's treasured historic resources. The photos in each calenda… Organized by Slice Administrator | Type: art, photo, contest
July 5, 2015 at 2pm to July 26, 2015 at 4:30pm – Lowndes Shakespeare Center Prince Gerwyn wants to marry the beautiful princess-but he'll have to get through her evil stepmother first. With her magical golden ball, the Step Queen casts a spell that turns Gerwyn into a slimy… Organized by Orlando Shakespeare Theater | Type: theater, family
July 9, 2015 from 7pm to 9pm – The Gallery at Avalon Island Creative City Project 2015 will bring Orlando to life with visual art and performance on October 17, 2015, and we want to dream and create with you! This year's event will include performances and in… Organized by Slice Administrator | Type: dance, art, performance
July 11, 2015 from 12pm to 2pm – The Gallery at Avalon Island As part of downtown's Third Thursday Gallery Hop, the Gallery at Avalon Island opens a new exhibition that brings together painters Tara Atefi, Matt Duke, Bethany Duvall, Brandon Geurts and Plinio Pi… Organized by Patrick Greene | Type: art, gathering
July 11, 2015 from 1pm to 4pm – CityArts Factory The Young Artists Group welcomes artist Janae Corrado as mentor artist for their July YAG Workshop! Janae works in oils in a style she describes as "dreamlike and surreal". She says "her work is a f… Organized by Meridith Olinger | Type: yag, workshop
July 16, 2015 all day – CityArts Factory "Action Painting" is an exhibit present by Del Cain featuring dripped and thrown art. Organized by Slice Administrator | Type: art, paint
July 16, 2015 from 6pm to 9pm – CityArts Factory A Solo Exhibition by Jonathan Yubi AirBorne Desire is a body of work that defines Jonathan Yubi's continued growth and interpretation of love and lust, the process of conquering and understanding su… Organized by Jonathan Yubi | Type: solo, exhibiton, art, opening


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Seven Black Bears Named America East Presidential Scholar-Athletes May 28, 2015 BOSTON, Mass. – The University of Maine had seven student-athletes receive the 2014-15 America East Presidential Scholar-Athlete Award, announced on Thursday, May 28, 2015. [read more]
What It Meant To Be A Black Bear May 6, 2015 Each year, the University of Maine asks selected student-athletes "What it meant to be a Black Bear". The following are quotes from some of our outstanding student-athletes: [read more]
Liis Emajoe Honored by College of Education May 1, 2015 | ORONO, Maine -- University of Maine senior Liis Emajoe (Tallinn, Estonia) was honored on Thursday night by the College of Education with an Outstanding Senior Award. She earned the Outstanding KPE -... [read more]
Video: Student-Athletes Give Back on Maine Day 2015 April 29, 2015 | The University of Maine Student Athletes participate on Maine Day 2015.
Soccer Honored with "Shining Stars Award" April 18, 2015 | Each year, the University of Maine women's soccer team participates in numerous community service projects, including the MS Walk of Brewer/Bangor. [read more]
Maine Elite Soccer Clinic Set for April 11 March 31, 2015 | ORONO, Maine -- The University of Maine women's soccer program is hosting a Maine Elite Soccer Clinic on April 11 at the Topsham Indoor Arena in Topsham, Maine. [read more]
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Insulin secretion plays a critical role in glucose homeostasis, and failure to secrete sufficient insulin is a hallmark of type 2 diabetes. Genome-wide association studies (GWAS) have identified loci contributing to insulin processing and secretion1,2; however, a substantial fraction of the genetic contribution remains undefined. To examine low-frequency (minor allele frequency (MAF) 0.5% to 5%) and rare (MAF<0.5%) nonsynonymous variants, we analyzed exome array data in 8,229 non-diabetic Finnish males. We identified low-frequency coding variants associated with fasting proinsulin levels at the SGSM2 and MADD GWAS loci and three novel genes with low-frequency variants associated with fasting proinsulin or insulinogenic index: TBC1D30, KANK1, and PAM. We also demonstrate that the interpretation of single-variant and gene-based tests needs to consider the effects of noncoding SNPs nearby and megabases (Mb) away. This study demonstrates that exome array genotyping is a valuable approach to identify low-frequency variants that contribute to complex traits.
Exome sequencing studies have discovered many low-frequency and rare coding variants3 that have yet to be examined systematically for association with complex traits. To determine the role of low-frequency coding variants in traits reflecting pancreatic beta-cell function, insulin sensitivity, and glycemia, we evaluated putative functional coding variants selected from exome sequences of >12,000 individuals (see Online Methods for a description of exome array design and content). We successfully genotyped 9,660 Finnish participants in the population-based Metabolic Syndrome in Men (METSIM) study4 for 247,870 variants on the Illumina HumanExome Beadchip. Clinical characteristics of 8,229 analyzed non-diabetic study participants are summarized in Supplementary Table 1. Among 242,071 variants passing quality control, 89,864 (38.1%) were variable in the studied individuals; of these, 71,077 were nonsynonymous, nonsense, or located in splice sites (Supplementary Table 2). We tested 59,029 variants with MAF>0.05% for association with insulin processing, secretion, and glycemic traits assuming additive allelic effects and using a linear mixed model to account for relatedness among study participants5.
We first evaluated rare and low-frequency coding variants at the nine signals previously identified by GWAS for fasting proinsulin level adjusted for fasting insulin (hereafter referred to as fasting proinsulin)1. To recognize independent association signals, we carried out conditional analysis adjusting for the known GWAS variants, all of which were represented on the exome array and replicated in METSIM (P<.01; Figure 1, Supplementary Table 3). Coding low-frequency variants at the known SGSM2 and MADD loci showed strong evidence of association (P<5×10−8; Table 1, Supplementary Figures 1 and 2). Previous studies highlighted several possible candidate genes at these loci1,6,7.
At SGSM2, rs61741902 (MAF=1.4%, P=8.9×10−10) encodes Val996Ile and is independent of GWAS variant rs4790333 (Pcond=4.8×10−10, r2=.001; Table 1, Figure 1, Supplementary Table 4). SGSM2 (small G protein signaling modulator 2) is a GTPase activating protein (GAP) that interacts with members of the Rab and Rap small G protein pathways and may act in a cascade of Rab-mediated steps in insulin secretory vesicle transport8–10. At rs61741902, the reference valine is well-conserved across vertebrates, and the isoleucine substitution is predicted to be damaging (Supplementary Table 5) Each additional copy of the minor allele was associated with an average increase of 0.41 standard deviations (SD) in fasting proinsulin (Table 1, Supplementary Figure 2). Still, the proportion of the trait variability explained is modest (0.47%; 95% CI = 0.22–0.82%) due to the low minor allele frequency. Identification of an independent and plausibly functional variant suggests that SGSM2 is the causal gene underlying the common fasting proinsulin GWAS signal.
At MADD, rs35233100 (MAF=3.7%, P=7.6×10−15) creates stop codon Arg766Ter and is in modest linkage disequilibrium (LD) with the lead GWAS variant rs7944584 (Pcond=.0001, r2=.17), and independent of the second GWAS variant rs1051006 (Pcond=5.0 × 10−16, r2=.02). The nonsense allele of rs35233100, associated with decreased proinsulin, is observed only on haplotypes containing the proinsulin-decreasing allele of rs7944584. Adjusting for one variant in a conditional analysis decreased, but did not eliminate, association for the other (P=4.9 × 10−25 and Pcond=5.7 × 10−15 for rs7944584; Table 1, Supplementary Table 4), suggesting biological contributions from the nonsense variant and an additional causal variant tagged by rs7944584. Of note, the trait-decreasing alleles of the two common GWAS-identified variants rs7944584 and rs1051006 tend to occur on different haplotypes, causing the evidence of association for either SNP to become dramatically more significant when adjusting for the other (rs1051006, P=0.033 and Pcond=2.7 × 10−8; rs7944584, P=4.9 × 10−25 and Pcond=8.3 × 10−31, Supplementary Table 4). Although the conditional association for the nonsense variant only achieves suggestive significance (P=.0001), it provides an especially plausible functional effect. The MADD nonsense variant is located in exon 13 of 36, suggesting that the mRNA would be targeted for nonsense-mediated decay11. MADD can act as a guanine nucleotide exchange factor for RAB3 proteins including RAB3A and RAB3B12, which are critical for insulin exocytosis13,14. Identification of a nonsense variant that contributes to the evidence of association suggests that MADD is a causal gene underlying the common GWAS signals.
LD at chromosome 11 from 46–57 megabases (Mb) and encompassing MADD has been reported to extend long distances15. Consistent with this, we noted significant or suggestive (P<1×10−5) fasting proinsulin association with nonsynonymous variants up to ~9 Mb away from the lead (noncoding) GWAS variant. Proinsulin-associated variants included rs628524, located ~9 Mb away and encoding Ser171Asn in the olfactory receptor OR5M11 (P=3.7×10−6 for fasting proinsulin; P as low as 5.0×10−10 for related traits) and rs7941404, located 376 kb away and encoding Arg349His in AGBL2 (MAF=11.8%; P=4.7×10−21). After adjusting for the three MADD variants (rs7944584, rs1051006, rs35233100), association significance for the distant variants was reduced by orders of magnitude (Supplementary Table 6, Figure 2). The fact that these associations were not eliminated suggests that additional variant(s) in this region await identification or that we may be adjusting for imperfect proxies of causal variants. These results also demonstrate that LD should be considered when interpreting GWAS results in this region. For example, the recently reported16 novel fasting glucose locus at OR4S1, represented by rs1483121, is in LD (r2=.19) with the lead and nonsense MADD SNPs ~1 Mb away (Supplementary Table 6).
Next, we tested coding variants across the genome for association with 19 traits measuring pancreatic beta-cell function, insulin sensitivity, and glucose levels. We identified two genes harboring low-frequency nonsynonymous variants with novel associations for fasting proinsulin levels: rs150781447 encoding TBC1D30 Arg279Cys (MAF=2.0%, P=5.5×10−11) and rs3824420 encoding KANK1 Arg667His (MAF=3.0%, P=1.3×10−8). The TBC1D30 variant was most strongly associated with late-phase proinsulin-to-insulin conversion (proinsulin AUC30–120; P=1.3×10−16) and the KANK1 variant with early-phase proinsulin-to-insulin conversion (proinsulin AUC0–30; P=1.6×10−9) (Table 2, Supplementary Figure 1). The TBC1D30 variant effect is large, with each additional copy of the minor allele resulting in an average increase of 0.50 SD in proinsulin AUC30–120 (Table 2, Supplementary Figure 2). This variant explained 0.94% of the trait variability (95% CI = 0.55–1.44%). We also observed a novel locus for insulin secretion as measured by the insulinogenic index, represented by nonsynonymous SNPs in PAM (smallest P=1.9×10−8) and PPIP5K2, located 200 kb apart, both with MAF=5.3%, and in near-perfect LD (r2=0.997) (Table 2, Supplementary Figures 1,2, and 3).
Common SNPs at GPSM1, HNF1A, and ABO, previously associated with other traits, are here associated with insulin secretion or beta-cell function in non-diabetic individuals (Table 2, Supplementary Figure 3). GPSM1 Ser391Leu is in LD with noncoding rs3829109 (r2=.69), previously associated with fasting glucose2. At ABO, the T allele of rs505922 is a proxy for the O blood group and has been associated with diverse phenotypes, including decreased pancreatic cancer risk17 and increased risk for duodenal ulcer18. Near HNF1A, rs2650000 was previously associated with LDL-cholesterol19 and C-reactive protein20; other HNF1A variants are associated with MODY3 (MIM #600496) and type 2 diabetes risk21.
TBC1D30 and KANK1 both function in G protein signaling and are strong biological candidates. TBC1D30 (TBC 1 domain family, member 30) encodes a GAP protein that likely regulates activity of specific Rab GTPases including RAB3A22 and RAB8A23. Rab3A knockout mice show a severe decrease in glucose-induced first phase insulin release and a 75% decrease in plasma insulin levels, without insulin resistance24. The reference arginine at rs150781447 is well-conserved across vertebrate species and the cysteine substitution is predicted to be damaging25 (Supplementary Table 5). The variant is located within a Rab-GAP domain and within the Kozak sequence of one TBC1D30 isoform and may alter translation initiation.
KANK1 (KN motif and ankyrin repeat domain-containing protein 1) plays a role in cytoskeleton formation by regulating actin polymerization26 and negatively regulates Rac1 and RhoA G protein signaling, pathways that have been implicated in insulin secretion27,28. At rs3824420, the reference arginine is not well conserved across species and the protein structure is predicted to tolerate the histidine substitution without an effect on function; this variant may still affect KANK1 or may tag another nearby variant. While rs3824420 has low frequency in Europeans (MAF=2.9% in Finns), it is common in East Asians (MAF=16%; Supplementary Table 7).
PAM encodes peptidylglycine alpha-amidating monooxygenase, an essential secretory granule membrane enzyme that catalyzes α-amidation of peptide hormones such as proinsulin29. Older mice heterozygous for Pam deficiency exhibit glucose intolerance30. At rs35658696, the reference aspartic acid is well conserved across vertebrates and located in one of the catalytic domains, and the glycine substitution is predicted to be damaging (Supplementary Table 5). The nearby gene PPIP5K2 is involved in cell signaling but has no known connection to insulin pathways. At rs36046591 in PPIP5K2, in near-perfect LD (r2=0.997) with rs35658696, the glycine substitution is predicted to be tolerated and the reference serine is not well conserved across species. This difference suggests that the PAM variant is causal at that locus, rather than the PPIP5K2 variant, but it is impossible to dissect them genetically.
Next, we carried out gene-based tests to investigate further the role of rare and low-frequency variants in insulin secretion and processing. Gene-based tests offer an alternative to single-variant tests, which are often underpowered to detect association with rare variants. Tests were performed on trait residuals adjusted for relatedness and covariates (see Online Methods). To address the impact of less common and rare variants, we considered only SNPs with MAF<3% or MAF<1%. In total, we tested 10,515 genes having at least two such variants using the SKAT-O test31.
We found significant associations between fasting proinsulin and TBC1D30, SGSM2, and ATG13 when using a MAF upper bound of 3% (Table 3, Supplementary Figure 4); by conditioning on the low-frequency variants detected by single-variant analysis, we demonstrated that these signals are driven by low-frequency variants. After adjusting for the common and nonsense variant signals at MADD, significance for ATG13, ~609 kb away, decreased by orders of magnitude (Table 3), showing that this signal is partially driven by the MADD variants and suggesting that other variants in this region await identification or that we may be adjusting for imperfect proxies of the causal variant. No additional associations were detected with other traits, including type 2 diabetes (data not shown).
In summary, we identified two low-frequency coding variants in genes at known loci and three novel genes with low-frequency variants associated with insulin processing or secretion. At least four of these genes play roles in G-protein signaling (Supplementary Figure 5). We show that the interpretation of both single-variant and gene-based tests needs to consider the effects of distant common SNPs, an especially important consideration when exome sequence data are analyzed without data on the surrounding noncoding regions. Although regions of long-range LD are unusual, at least 24 have been reported15 to extend >1 Mb in Europeans, a distance frequently used to claim independence of association signals in GWAS meta-analyses. Several of the identified exome array variants are plausibly functional, although ~25% and ~28% of low-frequency nonsynonymous variants on the exome array were annotated as conserved and plausibly damaging, respectively (Supplementary Table 2), and the exome array does not provide complete coverage of all functional variants at each locus. By the content of the exome array, this study was also limited in its ability to look at very rare variants. While sequencing will still be required to completely assess variants associated with insulin processing, secretion, and glycemic traits, this study provides proof-of-principle that exome array genotyping is a powerful approach to identify low-frequency functional variants and fine-map GWAS-identified loci in complex traits.
We attempted exome array genotyping of 9,717 participants in the Metabolic Syndrome in Men (METSIM) study4. Male study participants were randomly selected from the population register of Kuopio, Eastern Finland (population 95,000). Participants undertook a 1-day outpatient visit to the Clinical Research Unit at the University of Kuopio. Participants with diagnosed type 1 diabetes or type 2 diabetes (previously diagnosed, on diabetes medication, with fasting glucose ≥ 7 mmol/l, or with 2-hour glucose ≥ 11.1 mmol/l) were excluded from quantitative trait analysis. Clinical characteristics of non-diabetic study participants are provided in Supplementary Table 1. The study was approved by the ethics committee of the University of Kuopio and Kuopio University Hospital; informed consent was obtained from all study participants.
Clinical testing was performed following a 12-h overnight fast. A 2-h oral 75 g glucose tolerance test (OGTT) was performed with blood samples drawn at 0, 30, and 120 min, for measurement of plasma proinsulin, insulin, and glucose levels. Plasma specific proinsulin (Human Proinsulin RIA kit; Linco Research, St. Charles, MO; no cross-reaction with insulin or C-peptide) and insulin (ADVIA Centaur Insulin IRI, No. 02230141; Siemens Medical Solutions Diagnostics, Tarrytown, NY; minimal cross-reaction with proinsulin or C-peptide) were measured by immunoassay, and plasma glucose by enzymatic hexokinase photometric assay (Konelab System Reagents, Thermo Fisher Scientific, Vantaa, Finland).
Association results are reported for five traits: fasting proinsulin (adjusted for fasting insulin), early-phase (ProinsAUC0–30) and late-phase (ProinsAUC30–120) glucose-stimulated proinsulin-to-insulin conversion measured as proinsulin area under the curve (AUC) during the first 30 min and remaining 90 min of an OGTT, insulin secretion assessed by the insulinogenic index32, and a disposition index measure of β-cell compensation for insulin resistance defined as InsAUC0–30/GluAUC0–30 × Matsuda index of insulin sensitivity (Matsuda ISI)4,33. The reported associations were discovered by analyzing a total of 19 traits. Other measures of β-cell function included: oral glucose-stimulated proinsulin-to-insulin conversion during the first 30 min (ProinsAUC0–30/InsAUC0–30), and 30–120 min (ProinsAUC30–120/InsAUC30–120) of the OGTT, unadjusted fasting proinsulin, fasting proinsulin/insulin ratio, HOMA-β34, fasting insulin, insulin at 120 min, insulin AUC during the first 30 min (InsAUC0–30) and during 30–120 min (InsAUC30–120), and early-phase glucose-stimulated insulin release (InsAUC0–30/GluAUC0–30) adjusted for Matsuda ISI35. Indices of insulin sensitivity included HOMA-IR34 and the Matsuda ISI36. Associations with fasting and 120 min glucose were also tested. Supplementary Figure 6 shows correlations among traits. We calculated AUC measures using the trapezoid rule.
The Illumina HumanExome-12v1_A Beadchip includes 247,870 markers focused on protein-altering variants selected from >12,000 exome and genome sequences representing multiple ethnicities and complex traits. Nonsynonymous variants had to be observed three or more times in at least two studies, splicing and stop-altering variants two or more times in at least two studies. Additional array content includes variants associated with complex traits in previous GWAS, HLA tags, ancestry informative markers, markers for identity-by-descent estimation, and random synonymous SNPs. Details about SNP content and selection strategies can be found at the exome array design webpage (see URLs).
9,717 study samples, 104 blind duplicate samples, and 116 HapMap samples of different ethnicities were genotyped at the Genetic Resources Core Facility (GRCF) at the Johns Hopkins Institute of Genetic Medicine. Genotype calling was carried out using Illumina's GenTrain version 1.0 clustering algorithm in GenomeStudio version 2011.1. Cluster boundaries were determined using study samples. After clustering, 5,574 non-autosomal and 3,379 autosomal variants identified through filtering strategies developed at GRCF were manually reviewed and clusters edited as necessary. After technical failure and marker-level quality control, 242,458 of 247,870 (97.8%) attempted markers were successfully genotyped and had call rate >95% (average call rate 99.95%).
We evaluated genotyping quality using concordance rates for HapMap samples genotyped in our study and (a) sequenced by Complete Genomics or the 1000 Genomes Project (on-target regions of integrated phase 1 release; see URLs) or (b) genotyped on the Illumina HumanOmni2.5 Beadchip by the 1000 Genomes Project. These comparisons were based on 60,574, 117,063, and 39,056 overlapping variants and 17, 49, and 86 individuals, respectively. Overall concordance rates were 99.933%, 99.972%, and 99.956% for Complete Genomics and 1000 Genomes sequence data, and HumanOmni2.5 Beadchip data, respectively. Considering the external data as truth, concordance rates for homozygous genotypes were 99.982%, 99.987%, and 99.974%, and for heterozygous genotypes were 99.678%, 99.529% and 99.886%, respectively.
In total, 9,660 of 9,717 (99.4%) individuals were successfully genotyped (call rate > 98%). For the 242,458 SNPs that passed quality control, genotype concordance among the 104 blind duplicate sample pairs was 99.998%. Three sex-mismatched individuals were identified and excluded from subsequent analyses. One individual per pair of 6 known twin pairs and 6 unexplained apparent duplicates were excluded.
We carried out principal components analysis (PCA) twice, once excluding HapMap samples to identify population outliers, and then including HapMap samples to help interpret outliers. To avoid artifactual results due to family relatedness37, we computed principal components using SNP loadings estimated from a subset of 7,304 not-close-relatives. We defined close relatives as ones for whom estimated genome-wide identical-by-descent (IBD) proportion of alleles shared was >0.10. We estimated IBD sharing using PLINK's "--genome" option38 and carried out PCA using SMARTPCA37 on a linkage-disequilibrium-pruned set of 22,464 autosomal SNPs obtained by removing large scale high-LD regions15,39, SNPs with a MAF < 0.01, or SNPs with HWE P value < 10−6, and carrying out LD pruning using the PLINK option: "--indep-pairwise 50 5 0.2". Inspecting the first 10 PCs, we identified 12 population outliers, 9 of whom had self-reported non-Finnish ancestry; we excluded these 12 individuals from subsequent analysis. After further removal of 25 individuals with diagnosed type 1 diabetes, 1,376 with type 2 diabetes, and 3 with missing phenotypes, 8,229 individuals remained for quantitative trait analysis.
We tested for trait-SNP association assuming an additive genetic model using a linear mixed model to correct for relatedness using EMMAX5. We excluded SNPs with MAF < 0.05% or Hardy-Weinberg equilibrium (HWE) P value < 10−6. To reduce the impact of outliers, we log-transformed traits with skewed distributions and then Winsorized all traits at 5 standard deviations from the mean. All traits were adjusted for BMI, age, and age2 prior to association testing. We analyzed both untransformed residuals and rank-based inverse-normal transformed residuals to assess robustness of association results to distributional assumptions. Since no appreciable differences were observed between the two analyses, we report results for untransformed residuals. Finally, we visually inspected genotype cluster plots and checked HWE P values for all described variants. The lowest HWE P value for a reported novel associated variant was 0.09.
To correct for population stratification, we modeled population structure as part of the random effects, indistinguishable from the relatedness effect5. To investigate residual population stratification, we calculated genomic control inflation factors40 and inspected quantile-quantile (QQ) plots for test statistics both before and after removal of established and newly discovered loci (2 Mb segments centered on lead SNPs) (Supplementary Figure 7).
To identify additional association signals after accounting for the effects of known and newly discovered trait loci, we carried out conditional analyses where we included the allele count at the lead SNP(s) at the conditioning loci as covariate(s). To allow discovery of more than two association signals per locus, we used a stepwise procedure where additional SNPs were added to the model according to their conditional P value, as programmed in EMMAX5. We estimated LD metrics r2 and D' using 9,633 METSIM individuals who passed genotyping quality control. LD with SNPs not included on the exome array was determined based on whole-genome sequence data for 1,479 Northern European individuals.
For gene-based testing we used the SKAT-O31 test which encompasses burden tests and SKAT41 as special cases. SKAT-O has been shown to perform well under a range of scenarios, including scenarios in which protective, deleterious, and null variants are present, and in which a large number of variants are causal and associated in the same direction31. To account for relatedness, we adopted an approach similar to GRAMMAR42 by first obtaining trait residuals adjusted for relatedness using GenABEL43 and then carrying out gene-based testing. We performed analyses using default weights31 and MAF upper bounds of 1% and 3% for the combination of nonsynonymous, stop-altering, and splice-site variants. In total, 10,515 genes with at least two variants were tested. The results of the naive SKAT-O analysis and the analysis adjusted for relatedness were highly correlated (Supplementary Figure 8). To evaluate whether common or low-frequency SNPs associated with the trait in the single-variant analysis can account for a gene-based test signal, we also carried out conditional analyses by including the allele count at such SNP(s) as covariate(s).
We declared a single variant-trait association significant if the nominal P value was < 4.46 × 10−8, corresponding to a Bonferroni correction for 1,121,551 tests (19 phenotypes × 59,029 variants). We declared a gene-based test association significant if the nominal P value was < 2.50 × 10−7, corresponding to a Bonferroni correction for 199,785 tests (19 phenotypes × 10,515 genes).
We annotated variants relative to GENCODE version 7 coding transcripts44 using in-house developed software (unpublished). Amino acid substitution positions are relative to the canonical UniProt protein sequence45.
Exome array design, http://genome.sph.umich.edu/wiki/Exome_Chip_Design;
Complete Genomics 69 Genomes Data, http://www.completegenomics.com/public-data/69-Genomes;
The 1000 Genomes Project, www.1000genomes.org;
PLINK, http://pngu.mgh.harvard.edu/~purcell/plink;
SMARTPCA, http://genetics.med.harvard.edu/reich/Reich_Lab/Software.html;
EMMAX, http://genetics.cs.ucla.edu/emmax;
GenABEL, http://www.genabel.org
This study was supported by the Academy of Finland (contract no. 124243), The Finnish Heart Foundation, The Finnish Diabetes Foundation, TEKES (contract no. 1510/31/06), the Commission of the European Community (HEALTH-F2-2007-201681), and National Institutes of Health (NIH) grants DK093757, DK072193, DK062370, and 1Z01 HG000024. Genotyping was conducted at the Genetic Resources Core Facility (GRCF) at the Johns Hopkins Institute of Genetic Medicine.
AUTHOR CONTRIBUTIONSJ.R.H. led statistical analysis, and J.R.H., A.U.J., H.M.S., X.S., L.Y., and C.F. performed statistical analysis. J.R.H., M.P.F., M.L.B., and P.S.C. performed bioinformatics analysis. A.S., H.C., J.K., and M.L. obtained and analyzed phenotype data. J.M.R., H.L., I.M., R.I., E.W.P., and K.F.D. generated genotype data. B.M.N., M.L.D., and G.R.A. designed the genotyping array. H.M.K. and G.R.A. developed statistical analysis tools. J.K. and M.L. designed and supervised the METSIM study. J.R.H., M.P.F., M.L.B., M.B., and K.L.M. drafted the manuscript and all authors reviewed the manuscript. J.R.H., A.U.J., M.P.F., M.L.B., A.S., H.M.S., X.S., L.Y., C.F., T.M.T., L.J.S., F.S.C., G.R.A., R.M.W., M.B., M.L., and K.L.M. contributed to discussion and interpreted the data. M.B., M.L., and K.L.M. designed and supervised this study.
The authors declare no competing financial interests.
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