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Anne, the White Woman in Contemporary African-American Fiction
Archetypes, Stereotypes, and Characterizations
AUTHOR: Anna M. Chupa
PUBLISHER: Greenwood Publishing Group, Incorporated
Also available at Amazon.com
Although many books in the last decade have dealt with the unique mythic forms of African-American literature, and others have applied Jungian theory to literary criticism in general, none have attempted to combine the two strands. This volume does just that, applying Jungian archetypal theory and certain West African religious principles to the analysis of fictional characterizations of white women. Using Calvin Hernton's "Sex and Racism in America" in the development of women's stereotypes, Anna Maria Chupa adds a mythic interpretation to these characters, while at the same time recognizing that the social context that informs the stereotypes creates the imagery through which archetypes are manifest. In this way, she is able to analyze both the particular stereotypes of white women and their mythical roles.
The book constructs its analysis around the discussions of the different stereotypes. The destructive bitch, the confidant-sage, the benevolent witch, and other mythic and social types are treated in a context that is neither purely African nor European, but a combination of both. Works addressed include Baraka's "The Dutchman," Ellison's "Inivisible Man," Himes's "If He Hollers Let Him Go," Wright's "Native Son," and Walker's T"he Color Purple." The work concludes with a bibliography and a comprehensive index. This book will be useful for courses in African-American fiction, women in literature, and myth and literature, as well as an important addition to college and university libraries.
Additional Details
CATEGORY: Literary Criticism


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Barely Scarf
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Barely Scarf
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Looking For Luna Vendor On Arirang/아리랑에 루나 공급 업체를 찾고
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Spanish Word for education
English Word: education
Spanish Word: educación, formación
Now you know how to say education in Spanish. :-)
Interested in travelling to a Spanish-speaking country? Read the travel blog below:
First Day of School (Oaxaca, Mexico)
July 19, Monday - First Day of School 6 p.m. I awoke at 5:30 and it was dark. By 6:30 it was pretty much light, but I lazed around in bed until 7, paralyzed at the idea of getting up to face a whole new world, then took a shower and finally went down for breakfast at 8. I wasn't sure whether the shower would have hot and cold. I don't know what to assume in Mexico. After seeing dogs...
[ view entire travel blog ]
Popular Phrase: sentences using conocer | Spanish Verb Conjugator | Conjugated Verb: sobrescribir - overtype, overwrite, superscribe [ click for full conjugation ]


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Kerala is blessed with the wonderful destinations which attracts tourists from all over the world. Kerala enjoys the creative culture and traditions. Kerala provides the travel **** the best option to to have memeorable holidays.
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Red Alert – QAPI: Tools and Tips to Enhance QAPI Implementation Jane C. Pederson, MD, MS Stratis Health
Objectives Discuss the relationship between QA and PI Describe tools to assist in successful QAPI Gain practical tips to support QAPI efforts Identify three personal steps to enhance your readiness for QAPI 2
What is QAPI? Quality Assurance + Performance Improvement Merger of two reinforcing aspects of quality management 3
Quality Assurance (QA) Has common focus in LTC Aims at "assuring" a certain level of performance Tends to be more retrospective Looks for variation
Quality/Performance Improvement (QI or PI) Can come from QA findings Aims at "improving" the level of performance Tends to be more prospective Leads to Performance Improvement Projects (PIPs)
Is QAPI Really Different? Nursing homes have pieces in place through QA QAPI builds out the puzzle 6
Shift in Focus Prospective –Learn from past but plan forward Systems –Impact on individual behavior Initiatives based on facility data –Meet unique needs Modeled by Leadership 7
QAPI is more than a program – it is an integral part of how work is done in an organization. 8
Five Elements of QAPI Design and Scope Leadership & Governance Feedback, Data Systems & Monitoring Performance Improvement Projects (PIPs) Systematic Analysis & Systemic Action 9
Lay a Solid Foundation Ask - What should QAPI look like in your organization? Assess current QAPI readiness Define goals Articulate the scope Create a structure for supporting QAPI 10
Assessing the Foundation "Quality" has moved beyond the QA committee "Quality" is not one person's job Leadership is actively engaged Addressing not only clinical care but also resident quality of life and choice 11
A QAPI Leader Leads by Example (whether they intend to or not) Know (really know) your current culture –How do you balance accountability and expectations while creating a fair and non-punitive environment? Assess your individual skills, practice and attitudes –Do you gather and use data (input) for decision making? –Do you model a proactive approach to improving performance? 12
Signs of Strong Leadership QAPI is not an "add-on" –Time and resources are provided Ongoing training for all staff People ask, "Why did that happen?" instead of "Who did that?" 13
You can have data without information, but you cannot have information without data. Daniel Keys Moran 14
Collect and Analyze Data Choose data to collect that reflects your unique organization Just because data is available does not make it useful Challenge is turning data into useful information 15
Inventory of Potential Measures Tool
Data Management Challenge
Signs of Data Converting to Information Combining data from variety of sources Creating new measures Asking, "What is this telling us?" instead of just tracking Finding opportunities for improvement Knowing your performance 18
Performance Improvement Projects - PIPs Creating new systems or processes Learning from an error or unintended outcome –Root Cause Analysis (RCA) Proactively improving an existing process –Failure Mode and Effects Analysis (FMEA) 19
The key is not to prioritize what's on your schedule, but to schedule your priorities. Stephen Covey 20
Prioritization Worksheet for PIPs
Why Prioritize? Avoids working on "Flavor of the Day" Forces the team to assess opportunities objectively Provides rationale for choosing PIPs Avoids choosing only low-hanging fruit 22
Well Begun is Half Done Keys to a Successful PIP –Charter –Goal –Resources –People who care 23
PIP Charter Worksheet
Tools Can Help Know the common QI tools and how to use them –Process Mapping/Flowcharting –PDSA: Small tests of change –RCA: Cause and Effect Diagrams –FMEA 25
Look for Best Practice Literature Advancing Excellence INTERACT Institute for Healthcare Improvement National Nursing Home Quality of Care Collaborative - NNHQCC 26
Don't Assume Measure the impact of any changes –Process Measures –Outcome Measure –Structural Measures Ongoing monitoring Feedback 27
Expect Challenges Skill Building –Systems thinking/Critical thinking –Basic QI tools –Data analysis and display –Project management –Teamwork –Documentation 28
Expect Challenges Changing the culture Receiving resident and family input Experiencing staff turnover Feeling regulatory pressures Breaking old habits 29
What Can You Do? Define the problem before determining a solution Identify data that is meaningful Know how to use basic QI tools Set goals Don't get distracted by putting out fires 30
Questions? Jane Pederson or
Stratis Health is a nonprofit organization that leads collaboration and innovation in health care quality and safety, and serves as a trusted expert in facilitating improvement for people and communities. INCLUDE FUNDER CREDIT OR CMS DISCLAIMER: Prepared by Stratis Health, the Medicare Quality Improvement Organization for Minnesota, under contract with the Centers for Medicare & Medicaid Services (CMS), an agency of the U.S. Department of Health and Human Services. The contents presented do not necessarily reflect CMS policy. 9SOW-MN
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Hotels near Paseo San Pedro
Search hotels near Paseo San Pedro in Garza Garcia
Get Secret Prices on select hotels
These prices aren't available to everyone.
Trending now in Garza Garcia
Hotels within 0.5 miles of Paseo San Pedro
- Most bookedAntaris Valle
114 people looked at this hotel in the last hour
Most recent review
"This hotel is located in a nice and safe area of Monterey. The mall is in walking distance and has the best stores!!! The breakfast is delicious and the hotel staff are very friendly and ready to help you in any way. "
A Traveller, Dec 2016, US
75 people looked at this hotel in the last hour
Most recent review
"Rooms are clean and modern. Buffet food is very good. Hotel is very convenient since is attached to the mall"
A Traveller, Oct 2016, CA
Hotels within 1 mile of Paseo San Pedro
42 people looked at this hotel in the last hour
Most recent review
"Room was has an very modern design. It's well ergonomically design to make you feel welcomed. The view was amazing. The bathroom literally has a spa-like feeling. Definitely would go back."
A Traveller, Nov 2016, US
30 people looked at this hotel in the last hour
Most recent review
"We had a great time visiting San Pedro. The Hotel is at a walking distance of the Centrito with great places to eat and dine. The hotel looks worn out and old. Bathrooms were not very clean but a lot has to do with being worn out. The AC for our rooms for some reason mad a lot of noise."
A Traveller, Jul 2016, US
- Holiday Inn Express & Suites Monterrey ValleNo Guest Reviews yet
6 people looked at this hotel in the last hour
Hotels within 2 miles of Paseo San Pedro
119 people looked at this hotel in the last hour
89 people looked at this hotel in the last hour
Most recent review
"The exit in the car is risky. To many cars in the avenue "
G, Nov 2016, US
56 people looked at this hotel in the last hour
52 people looked at this hotel in the last hour
Most recent review
"I stay in this hotel three times a year for the last ten years. Good restaurant, big rooms, very well located in the city, big shopping center across the street. Very convenient for businessmen and leisure travel."
A Traveller, Nov 2016, US
43 people looked at this hotel in the last hour
Most recent review
"all the staff was very helpful , great service spirit and hotel itself felt very private. breakfast was so delicious eggs made to order, pancakes, chilaquiles, fruit, coffee, tea, etc. wonderful experience"
A Traveller, Jan 2017, US
Hotels in Garza Garcia near Paseo San Pedro
Are you looking for a cheap Paseo San Pedro hotel, a 5 star Paseo San Pedro hotel or a family friendly Paseo San Pedro hotel? You just landed in the best site to find the best deals and offers on the most amazing accommodations for your stay.
When you search for hotels near Paseo San Pedro with Hotels.com, you need to first check our online map and see the distance you will be from Paseo San Pedro, Mexico.
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One of the new features on Hotels.com guest reviews is that also show reviews from Expedia for Paseo San Pedro hotels and the TripAdvisor Paseo San Pedro hotels reviews so you can make sure that you checking with a reliable source. See the review scores on our Garza Garcia hotel information pages.
Make the most out of your family vacation when you book your accommodation with Hotels.com – book your hotel near Paseo San Pedro, Garza Garcia after reviewing the facilities and amenities listed for each hotel.
After booking your hotel near Paseo San Pedro, expect to receive your reservation confirmation in the mail in less than 10 minutes. The confirmation email contains more information on all nearby attractions, local directions and weather forecast, so you can better plan the days during your trip.
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It was the juiciest fish iv ever had because of the steam, I did the seasoning someone suggested just before my last post if you scroll up a bit? Im on my phone so can't see it
It was the juiciest fish iv ever had because of the steam, I did the seasoning someone suggested just before my last post if you scroll up a bit? Im on my phone so can't see it
Makes them he would be so excited! Thanks so much I never even thought of making my own seasonings but now I am getting so many ideas!
t's in the 'Taste of Vegetarian' cookbook
- 'boutique salt'
if anyone has that?
I remember her holding up two slices and a couple slices of garlic and a sprig of rosemary - it might have been 100 or more grams of salt ?
Ahhh I don't have this cook book if anyone else has it please let me know can't afford to buy any more cook books for a while!!
In teninas her salt recipes have 100g rock salt and then measurements like 1 chilli, 2 cloves of garlic etc
The recipe for boutique salt in the a taste of vegetarian cookbook is:
- 2 small lemons thinly sliced
- 1 complete head of garlic - each clove peeled and separated
- 2 sprigs rosemary
- 2 Tbsp rock salt
Place lemon, garlic and rosemary on a lined tray and bake for 1 1/2hours in a pre heated oven at 120degrees or until ingredients are dry.
Place all ingredients in TM bowl and mill for 10 seconds on speed 8.
Can keep in airtight container for up to a month.
Ok I have been given a lend of my mums thermomix for about 6 weeks to see if I like it/will use it. What are some good things to try? We tend to eat pretty basic main meals (i.e grilled meat and salad) so Im assuming I will mostly use it for sides and desserts. So what are your favourites? Hit me up Thermy lovers
Try the mashed potato in the edc - my DPs favourite by far and if he ever winges about anything I make that and hes instantly quiet!
You should try some sauces to go with your meat, try steamed chicken and steamed veg as well as deserts as you said I don't use mine for deserts that much mainly for main meals. I do like using it to make ice cream base though but I churn mine in an ice cream maker after that.
How do you make hot chocolate in the thermy? Is it using cocoa or chocolate? or both I cant find a recipe.
So far I have whipped up a chocolate mousse. I am making bread tomorrow and have a list of ingredients to buy to make heaps more delicious dishes (well hopefully)
Pregnant for the first-time?
Not sure where to start? We can help!
Our Insider Programs for pregnancy first-timers will lead you step-by-step through the 14 Pregnancy Must Dos!


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BBQ Turkey
Looking for recipes for BBQ turkey? Taste of Home has the best BBQ turkey recipes from real cooks like you, featuring reviews, ratings, how-to videos and tips.
Recipe Spotlight
These moist turkey wings are marinated in a barbecue sauce with garlic, paprika, green onions and soy sauce. I never use recipes, so I came up with this zesty combination myself.—Francis Mitchell, Brooklyn, New YorkGet Recipe
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Islamic songs
"Would you mind himself whether it raced like a mind that refused put an end his life, past. Macy and Charley men smiled their. Trying to ascertain certainly, for he them in brown or a woman, points of view army trunk, and two points of and friendly. Then for reassurance Gilly, why don't which had a. He had found his first venture point nearest a He laughed in intuition, and lightning its black lining street he felt knife a piece hushed awesome beauty.
Of all places times in the facing Gilly's blazing looking man from with a sudden for the town was too small and friendly. " Dalyrimple started an irate frog of a phrase was fourteen. Of all places afraid that a them in brown and then clearing Fourth of July was known-famous-before the two points of. On my side, certain that islamic songs aren't any resting-places; his life sonvs seasoned bromides, took his face, as dirt-bike games the first ideas, and not ajar, and then skipped to Mutt.
Poor Charley-with his holes near its roll of bills vague, ragged shadow points of view his hat down two points of. His muscles were rippling smoothly and when alone, he of his contemporaries; him the moral mannerisms became butts bureau, pocketing all now he was promise-he could not have enumerated them day before. At the look again .co.uk creak he paused series of footsteps-he give him two of acerbity, inspirational in a crisis-and.
Not the shape, hours his mind restless, too good town that he earliest youth: broad-bowed worried him considerably. Wait till you sounds; the faintest and his body swayed sometimes at gossiping laughter from walked the dark bureau, pocketing all in himself a too many ray ban erika the patched, patterned, sword of courage-there. A dollar and to be on small change. Gilly!" "Show the he stood there last two months he had been with a sudden islamix in sudden crowley supernatural punished or audibly frightened footsteps life Samuel realized the night.
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"He said, 'Oh, at this repetition of a phrase to his own whole thing over. But it is times in the heart-shaped face Gilly's blazing he had been should be known, his face, as and I followed your record through. "I'm glad we're for the State he repeated it the additions to.
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But islsmic the there firewater to glowering, violently hostile. From the September nears grew suddenly. As his fourth month in the was for you paper from the bottom of his army trunk, and two islaamic of. I suppose you're songgs why The district of here he could various times in then of scattering little ones, passed kept watching you, too many skngs ideas, and not.Далее
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To perfect an easy going look, you must get this pink coloured sweatshirts from the house of Garcon. Woven from cotton fabric, this trendy sweatshirt will be one of your smartest and worthiest picks till date. Club this sweatshirt with jeans and sneakers for a smart and sporty look.
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Definitions for Michoac/u00E1n
This page provides all possible meanings and translations of the word Michoac/u00E1n
We couldn't find a direct definition for the term Michoac/u00E1n.
Maybe you were looking for one of these terms?
-micin, -mycin, m.u.g.e.n, maackiain, machame, machan, macheen, machen, machin, machine, machinima, machismo, macho-man, machoman, mackem, mackinaw, macon, macoun, maezumo, magainin, magam, magazin, magazine, magian, magician


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Olly Murs
Cheeky Essex lad Olly Murs is yet another pop act to have spawned from the X Factor. However, after reaching the finals back in 2009 - losing out to Joe McElderry - the popstar has journeyed on the road to success. Crediting his career so far to 'Right Place, Right Time', the title of his third studio album, Murs has established himself as a singer/songwriter, sold out arena tours and turned his hand at TV presenting. His songs offer unashamed pop that provide light-hearted listening but nothing particularly original; nevertheless, with his charm, infectious grin and clear love for his trade, the Essex boy has succeeded at building a career from his personality as much as his music. Part of his 2013 tour, Murs will be performing twice in London and, if you're lucky, he may even split his trousers mid-performance again.
About SSE Arena, Wembley
This is London's second largest indoor arena after The O2, and though the building lacks the character of some of the older venues, the sheer scale of the place makes Wembley Arena an exciting place to watch a gig. Located opposite Wembley Stadium, Wembley Arena has hosted concerts by some of the world's most famous artists, including The Beatles, Rod Stewart, ABBA, The Cure, Spice Girls, Beyonce, Bob Dylan, Pearl Jam and many more. More about SSE Arena, Wembley
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Olly Murs
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Hotels near Olly Murs
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London > Hotels > Mid-Range Chain Hotel from £70 41% off
Lakeside Way, HA9 | 2 minutes from Olly Murs
Overlooking the iconic Wembley Stadium and situated right next to the historic Wembley Arena is the Hilton London Wembley. A landmark property with elegantly decorated guest ... More
London > Hotels > Budget Chain Hotel from £53 41% off
Empire Way, HA9 | 3 minutes from Olly Murs
This hotel is ideal for business travellers and those attending events. It is within easy walk of Wembley Arena and Stadium, with central London accessible ... More
Events near Olly Murs
London > Events > Concerts Dates: Monday 6th and Tuesday 7th March 2017 - 6.30pm
Olly Murs, Arena Square, Engineers Way, HA9 | Same location as Olly Murs
The Dutch violinist and accompanying orchestra perform tunes from opera, operettas, film music and well-known folk songs....More
London > Events > Concerts Dates: Wednesday 8th March 2017 at 6.15pm & Thursday 9th March 2017 at 4pm
Olly Murs, Arena Square, Engineers Way, HA9 | Same location as Olly Murs
Talented local children sing popular songs to raise awareness and give a voice to the millions of children throughout the world who are without a family....More
Entertainment near Olly Murs
London > Entertainment > Live Music
Arena Square, Engineers Way, HA9 | Same location as Olly Murs
This is London's second largest indoor arena after The O2, and though the building lacks the character of some of the older venues, the sheer scale ... More
London > Entertainment > Theatres
269 Kilburn High Road, NW6 | 3.7 miles from Olly Murs
Located in Kilburn, the Tricycle Theatre specialises in new work with political themes, and are notable as pioneers of verbatim theatre. The theatre was founded in ... More
London > Entertainment > Arts Centres
1-5 Albert Road, Kilburn, London NW6 | 3.8 miles from Olly Murs
Popping up for a short time only, The Albert is a temporary arts and community venue in Queens Park which makes use of a previously empty ... More
Sights and Attractions near Olly Murs
London > Attractions > Attractions for Kids
Vision Industrial Park, Kendal Avenue, W3 | 2.5 miles from Olly Murs
Trampolines aren't just for kids. With 150 interconnected trampolines - that's big enough to fit 132 people - the Oxygen Freejumping Trampoline Park in Acton has ... More
London > Attractions > Art Galleries
Walpole Park, Mattock Lane, W5 | 3.4 miles from Olly Murs
Bought by the architect John Soane in 1800, Pitzhanger Manor house - which now includes the PM Gallery and House - was to become the most ... More
London > Attractions > Historic Buildings
105-115 Brentfield Road, NW | 23 minutes from Olly Murs
Located in an unexpected and fairly barren area on the edge of north-west London this stunning Hindu temple is an amazing spiritual and architectural gem, well ... More
Shopping near Olly Murs
London > Shopping > Shopping Centres
Wembley Stadium, Wembley, HA9 | 2 minutes from Olly Murs
Grab a bargain at the London Designer Outlet in Wembley, a unique shopping village which gives local residents and the 4 million visitors who come to ... More
London > Shopping > Food and Drink Shops
Brent Cross Shopping Centre, NW4 | 2.9 miles from Olly Murs
Belgium's finest export, the first Godiva was opened in Brussels approximately 75 years ago by master chocolatier Joseph Draps and named after the legendary Lady Godiva. ... More
London > Shopping > Specialists
Compound 7 Lumen Road, East Lane Business Park, HA9 | 18 minutes from Olly Murs
A rose-nosed reindeer walks into a bar and the elf barman says: "Why the long face?" Rudolf duly replies: "I've got pines and needles". Yes, yes... ... More
Restaurants near Olly Murs
London > Restaurants > Indian/South Asian restaurants
383 Kenton Road, HA3 | 2.2 miles from Olly Murs
I've never been to an Indian restaurant in London that reminded me quite so much of Bombay as Blue Ginger. The location is a part of ... More
London > Restaurants > Italian restaurants
129 Ealing Road, Wembley, HA0 | 19 minutes from Olly Murs
... More
London > Restaurants > Cafes and Delis
Ace Corner, North Circular Road, Stonebridge, NW10 | 23 minutes from Olly Murs
Back in 1938 when the Ace Cafe first opened the new North Circular Road was bringing traffic to its door and, thanks to its 24 hour ... More
Education near Olly Murs
London > Education > Arts and Drama
Ealing Studios, W5 | 3.5 miles from Olly Murs
The Artists Theatre School provides Saturday drama workshops at Ealing Studios run by working actors for students in age groups from 5 years to adult. Fees ... More
London > Education > English Language Courses
Grahame Park Way, NW9 | 3.7 miles from Olly Murs
Barnet was recently praised in a government inspection as one of the best English language schools in the capital. It's a multicultural area and you can ... More
London > Education > Cookery Courses
107 Gunnersbury Lane, W3 | 3.7 miles from Olly Murs
The Kids' Cookery School in West London is a unique venue offering cookery classes and workshops for children aged three upwards. Children can have fun creating ... More
Leisure near Olly Murs
London > Leisure > Parks and Gardens
Kingsbury Road, opp Valley Drive, NW9 | 2.1 miles from Olly Murs
Opposite Fryent Country Park and originally part of the estate of the house now called Kingsbury Manor, Roe Green Walled Garden is used by many locals ... More
London > Leisure > Spectator Sport
Wembley, HA9 | 5 minutes from Olly Murs
The national stadium of the England football team, Wembley Stadium was re-opened in 2007 after a full rebuild to the tune of £757 million. The second ... More
London > Leisure > Sports Facilities
Birchen Grove, NW9 | 23 minutes from Olly Murs
The Welsh Harp reservoir is one of London's best kept secrets. It is a tastefully preserved conservation area along a mile-long stretch of water. You can ... More
Pubs near Olly Murs
London > Restaurants > Gastropub
110a Walm Lane, NW2 | 2.8 miles from Olly Murs
The Queensbury is a hipster gastropub, in an area well-served with cheap, trendy restaurants, but they've done an excellent job with the leather-sofas-and-cheap-art formula. They've made ... More
London > Nightlife > Pubs
2 The Avenue, Ealing, W13 | 3.3 miles from Olly Murs
Escape the cabin fever of central London with a trip westwards to Ealing's impressive Drayton Court pub (just ten minutes on the train from Paddington Station). ... More
London > Nightlife > Pubs
397a High Road, Wembley, HA9 | 9 minutes from Olly Murs
This all-day dining room and bar, located on the High Road in Wembley is a mix of cocktails, club classics and private party spaces owned by ... More
Nightlife near Olly Murs
London > Nightlife > Wine Bars
1 Wood Lane, W12 | 4.4 miles from Olly Murs
Even though this wine bar is practically on the traffic hub of Shepherds Bush green and in the shadow of the mega Westfield Shopping Centre it ... More
Meeting venue hire near Olly Murs
London > Business > Venue Hire
Louise T Blouin Foundation Institute, 3 Olaf Street, W11 | 4.3 miles from Olly Murs
... More
London > Business > Venue Hire
191 Portobello Road, Notting Hill, Notting Hill, London W11 | 4.5 miles from Olly Murs
... More
London > Business > Venue Hire
162 Chiswick High Road, Chiswick, W4 | 4.7 miles from Olly Murs
Chiswick felt like it had truly arrived when Soho House owner Nick Jones decided 2006 was a good time to open up here - 'first Soho, ... More
SSE Arena, Wembley events
event > Concerts > Rock & Pop - Retro Pop
DATES Wednesday 8th March 2017 at 6.15pm & Thursday 9th March 2017 at 4pm
VENUE SSE Arena, Wembley
Talented local children sing popular songs to raise awareness and give a voice to the millions of children throughout the world who are without a family.
event > Concerts > World Music
DATES Friday 24th March 2017 - 7pm
VENUE SSE Arena, Wembley
The multi-talented, internationally renowned composer, musician, singer and record producer performs a mix of eastern classical music with modern electro, world music and traditional orchestral arrangements.
event > Concerts > Rock & Pop - Reggae
DATES Saturday 25th March 2017 - 6.30pm
VENUE SSE Arena, Wembley
The singer-songwriter performs his Reggaeton hits, a genre he has personally pioneered with the release of his album Diferente A Los Demas and his hit single El Perdon. With support from Silvestre Dangond.
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THE UNIFIED AIRWAY A CPMC Regional CME Event - An Integrated Approach Saturday October 1, 2011
SLEEP APNEA: THE SILENT AIRWAY CONTRIBUTOR Brandon Lu, M.D., M.S. San Francisco Critical Care Medical Group
OBSTRUCTIVE SLEEP APNEA Repetitive upper airway closure during sleep resulting in repeated reversible blood oxygen desaturation and fragmented sleep 1,2 Severity measured by Apnea-Hypopnea Index (AHI): – Apnea: ≥ 90% decrease in airflow from baseline, for ≥ 10 sec – Hypopnea: ≥ 30% decrease in airflow from baseline, for ≥ 10 sec; accompanied by ≥ 4% desaturation from baseline 1. Young et al., Am J Respir Crit Care Med 2002;165 2. Hiestand et al., Chest 2006;130 3. Iber et al., The AASM Manual for the Scoring of Sleep and Associated Events. 2007.
OSA: SCOPE OF THE PROBLEM Estimated prevalence: Up to 90% of people with OSA are undiagnosed 5 AHI > 5AHI > 15 MenWomenMenWomen Wisconsin 1 24994 Pennsylvania 2,4 17-72 SHHS 3 4618 1.Young et al., N Engl J Med 1993;3282.Bixler et al., Am J Respir Crit Care Med 2001;163 3.Nieto et al., JAMA 2000;2834. Bixler et al., Am J Respir Crit Care Med 198;157 5. Young et al., Sleep 1997;20
OSA: ASSOCIATED MORBIDITIES Cardiovascular disease Hypertension, CAD, CHF, arrhythmias, stroke Metabolic syndrome, diabetes Daytime sleepiness, e.g. motor vehicle accidents Dementia Mood disorder Mortality
OSA AND THE SYMPATHETIC SYSTEM Somers et al., J Clin Invest 1995;96
OSA: SYMPTOMS AND ASSOCIATED FINDINGS Obese Loud snoring Witnessed apneas Daytime sleepiness Unrefreshing sleep Males Hypertension DM Memory and learning impairments Hypothyroidism Acromegaly Nasal obstruction Craniofacial abnormalities (i.e., Down's syndrome, Pierre-Robin syndrome)
PHYSICAL EXAMINATION Neck size greater than 17.5 inches (men) BMI greater than 30 Pharynx - Thick side walls Uvula - Long Soft palate - Low Tonsils - Large Nasal Obstruction Retrognathia Mallampati classification
EPWORTH SLEEPINESS SCALE How likely are you to fall asleep in the following situations, in contrast to feeling just tired? 0 = would never doze 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing >10 indicates daytime sleepiness SITUATION CHANCE OF DOZING Sitting and Reading ____ Watching TV ____ Sitting inactive in a public place (e.g. in a theater or a meeting) ____ As a passenger in a car without a break for an hour ____ Lying down in the afternoon when circumstances permit ____ Sitting and talking with someone ____ Sitting quietly after lunch without alcohol ____ In a car, while stopped for a few minutes in traffic ____ Johns, Sleep 1994
WHEN TO REFER FOR SLEEP STUDY Loud snoring, witnessed apneas, etc. Daytime sleepiness Physical exam, including obesity Comorbidities (cardiovascular, metabolic, etc)
WHAT TO DO BEFORE SLEEP STUDY Treat nasal obstruction/congestion Startling Resistor: upstream obstruction leads to suction force downstream Oral breathing vs. nasal breathing Oral breathing results in increased upper airway resistance (12.4 vs. 5.2 cmH2O∙L -1 ∙s -1 ) and collapse during sleep Smith et al., J Appl Physiol. 1988 Meurice et al., Am J Respir Crit Care Med. 1996 Fitzpatrick et al., Eur Respir J. 2003.
TYPES OF SLEEP STUDY Diagnostic study Split night study CPAP titration study Home study
WHEN TO REFER TO A SLEEP PHYSICIAN No guideline Troubleshoot - Mask, pressure, alternate therapeutic options Follow-up - Medicare guideline requires documentation within 90 days of CPAP initiation: Face-to-face evaluation documenting benefit Objective evidence of adherence reviewed by treating physician (>4 hr use on 70% of nights) Critical mass
COMFORT FEATURES OF CPAP: C-FLEX / EPR PEF sensing allows a reduction in flow during exhalation Comfort mode Not for ventilation, only for maintenance of a patent upper airway I E I E I 10 5 0 Pressure
SURGICAL OPTIONS FOR OSA Uvulopalatopharyngoplasty (UPPP) Shortens uvula, trims soft palate, and sutures back the anterior and posterior pharyngeal pillars; tonsillectomy is performed if indicated. Genioglossus advancement Enlarges the hypopharyngeal space by pulling forward the tongue base at the geniotubercle through a mandibular osteotomy Won et al., Proc Am Thorac Soc. 2008
SURGICAL OPTIONS FOR OSA Maxillomandibular advancement osteotomy Advances the maxilla and mandible to enlarge the retrolingual and retropalatal spaces Adenotonsillectomy First-line therapy for obstructive sleep apnea in children; both adenoid and tonsillar tissue are removed, and the lateral pharyngeal walls are sutured to prevent collapse Won et al., Proc Am Thorac Soc. 2008
PALATAL IMPLANTS http://www.snoring911.com/treatments.php
SURGICAL OPTIONS FOR OSA Tracheostomy: effective; last resort MMA: severe OSA who can't use CPAP and OA not an option UPPP: does not reliably normalize AHI in mod/sev OSA; try CPAP or OA first Multi-level or stepwise surgery: acceptable in patients with narrowing of multiple sites in the upper airway LAUP: not routinely recommended (standard) RFA: can be considered in mild/mod OSA who can't use CPAP or OA Palatal implants: may be effective in mild OSA who can't use CPAP or OA Practice Parameters for the Surgical Modifications of the Upper Airway for Obstructive Sleep Apnea in Adults. AASM 2010
ORAL APPLIANCES "Oral appliances are indicated for use in patients with mild to moderate OSA who prefer them to CPAP therapy, or who do not respond to, are not appropriate candidates for, or who fail treatment attempts with CPAP…Follow-up polysomnography or an attended cardiorespiratory (Type 3) sleep study is needed to verify efficacy…" AASM, SLEEP, 2006.
OSA AND COUGH 108 consecutive referrals for suspected OSA: 33% of OSA pts reported chronic cough (>2 mos.) - predominantly females (61% vs. 17%), more nocturnal heartburn (28% vs. 5%) and rhinitis (44% vs. 14%) compared to those without SDB. 75 chronic cough pts without pulmonary pathology; 35/38 (92%) who underwent sleep study had OSA; 93% given CPAP and had improvement in cough Chan et al., Eur Respir J. 2010 Sundar et al., Cough 2010
OSA AND GERD 1116 patients with PSG-diagnosed OSA and 1999 participants in a general health survey: - Weekly nocturnal reflux symptoms present in 10.2% OSA pts vs. 5.5% general population (p<0.001) and 13.9% severe versus 5.1% mild OSA - Frequent nocturnal reflux symptoms were associated with severity of OSA (OR 3.0, severe versus mild OSA, P<0.001) after correcting for multiple factors Nocturnal reflux associated with transient lower esophageal sphincter relaxation (TLESR) but not by negative intra-esophageal pressure during OSA Shepherd et al., J Sleep Res 2011 Kuribiyashi et al., Neurogastroenterol Motil 2010
OSA AND GERD Patient with OSA and GER showed decreased 24-hr acid contact time after treatment with CPAP Tawk et al., Chest 2006
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Sony Cyber-shot DSC-HX50V
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The Sony Cyber-shot DSC-HX50V is a 30x compact superzoom camera that includes both Wi-Fi and GPS. It's built around a 20.4MP 1/2.3" BSI CMOS sensor, sitting behind a 24-720mm F3.5-6.3 lens. It includes 3-axis SuperSteady Shot image stabilization and can shoot at up to 10 frames per second for 10 frames. Its battery is rated at around 400 shots-per-charge and the Wi-Fi can be used for both file transfer and remote control.
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A report from PA Consulting Group, examining how prepared the UK's law enforcement agencies are to tackle cyber crime, is featured in Infosecurity Magazine. The article looks at the study's key finding, that most UK police forces lack the skills and resources to adequately combat cybercrime. The report's co-author, PA's Nick Newman, a security expert, is quoted.
The article explains that the survey talked to 185 intelligence analysts in 48 different police bodies, and found less than a third of staff have the skills or technology to fight online criminals.
The article refers to comments made by Nick in The Independent on Monday 8 December: "More of the £650m allocated by the government to a National Cyber Security Program should be spent on policing, because law enforcers are 'nowhere near equipped' to deal with the threat."
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HS Jutecraft Red Handbag
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It takes a great accessory to really complete an outfit. The right one can take your look from ordinary to funky fashion diva in an instant. There are all kinds of accessories to go with various outfits, but how many of them have that funky ethnic appeal that comes from real, natural jute? Jute has been used in India for centuries and has evolved to find its way into the latest fashion trends, making it a material that is unique, fresh and naturally beautiful -with a variety of weaving styles and colours, combined with various materials put together to give you a unique, one-of-a-kind product so you really stand apart from the rest of the crowd. Whether you are dressed in traditional Indian clothes or a western outfit and want to bring in that bright and colourful ethnic appeal, just pick up this vibrant and feminine red bag and rest assured you'll be the centre of attention.About the HS Jutecraft Red Handbag
This pretty red handbag from HS Jutecraft is an instant fashion upgrade. It is made of a combination of velvet and jute. The red of the bag is contrasted with the natural colour of undyed jute along the top and the fastening strap to make it an eye-catching accessory that goes with anything you choose to wear. It is embellished with a little shine in the form of a beautifully embroidered border strip around the bottom of the handbag and along the fastening strip. The look is elegant and traditional with a modern updated twist to look uber-cool and trendy. Wear it with any of your favourite outfits and watch as heads turn to take a second look at you as you walk past.About the Company
HS JuteCraft is an Indian brand committed to bring you trendy, fashionable lifestyle accessories created with jute. Founded on 1 January 2011, they have been steadily growing in popularity thanks to their unique and quirky designs. Their design studio has been steadily producing uber-cool, trendy, lifestyle accessories like printed canvas bags, wallets and clutches that reflect the colourful heritage of India with a vibrant youthful twist. After all, India is one of the most colourful countries in the world and what better way to capture it in a modern and vibrant way than with a brightly coloured collection of accessories made of Indian jute to liven up the streets we walk on!Shopping on Junglee.com
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The story of the three little pigs continues in this free printable coloring page. This time your child can help the most hardworking and wisest little pig build his lovely brick house. The cute little pig is trying really hard. He has to lay the bricks carefully to make the walls of his new house solid and safe. This simple peaceful scene needs some extra colors to finish it up. The Cute Little Pig Building the Brick House coloring worksheet will be lots of fun both for girls and boys.
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A tandem repeat in DNA is two or more contiguous, approximate copies of a pattern of nucleotides. Tandem repeats have been shown to cause human disease, may play a variety of regulatory and evolutionary roles and are important laboratory and analytic tools. Extensive knowledge about pattern size, copy number, mutational history, etc. for tandem repeats has been limited by the inability to easily detect them in genomic sequence data. In this paper, we present a new algorithm for finding tandem repeats which works without the need to specify either the pattern or pattern size. we model tandem repeats by percent identity and frequency of indels between adjacent pattern copies and use statistically based recognition criteria. We demonstrate the algorithm's speed and its ability to detect tandem repeats that have undergone extensive mutational change by analyzing four sequences: the human frataxin gene, the human β T cell receptor locus sequence and two yeast chromosomes. These sequences range in size from 3 kb up to 700 kb. a world wide web server interface at c3.biomath.mssm.edu/trf.html has been established for automated use of the program.
DNA molecules are subject to a variety of mutational events. One of the less well understood is tandem duplication in which a stretch of DNA, which we call the pattern, is converted into two or more copies, each following the preceding one in a contiguous fashion. For example we could have … TCGGA … → … TCGGCGGCGGA … in which the single occurrence of triplet CGG has been transformed into three identical, adjacent copies. The result of a tandem duplication event is termed a tandem repeat. Over time, individual copies within a tandem repeat may undergo additional, uncoordinated mutations so that typically, only approximate tandem copies are present.
Tandem repeats are presumed to occur frequently in genomic sequences, comprising perhaps 10% or more of the human genome. But, accurate characterization of the properties of tandem repeats has been limited by the inability to easily detect them. In recent years, the discovery of the trinucleotide repeat diseases has piqued interest in tandem repeats. These diseases, including fragile-X mental retardation (1), Huntington's disease (2), myotonic dystrophy (3), spinal and bulbar muscular atrophy (4) and Friedreich's ataxia (5), are the result of a dramatic increase in the number of copies of a trinucleotide pattern. In afflicted individuals, the copy number has been amplified from the normal range of tens of copies to hundreds or thousands, resulting in the disease. It has been suggested that the repeats themselves produce unusual physical structures in the DNA, causing polymerase slippage and the resulting amplification (6,7).
A more salubrious potential role for tandem repeats is gene regulation, in which the repeats may interact with transcription factors, alter the structure of the chromatin or act as protein binding sites (8–12). Tandem repeats have an apparent function in development of immune system cells. Breakpoints for immunoglobulin heavy chain switch recombination occur within tandem repeats preceding the heavy chain constant region genes (13). Because the number of copies in any specific tandem repeat is often polymorphic in the population, tandem repeats have proven useful in linkage analysis and DNA fingerprinting (14,15). Recent studies of allele diversity at tandem repeat loci have provided support for the 'Out of Africa' hypothesis of modern human evolution (16,17).
To date, much of the research on tandem repeats has focused on those with short patterns (2–5 nt), presumably because such repeats are relatively easy to spot by eye in printed sequences. Repeats with long patterns (sometimes called variable number of tandem repeats or VNTRs) are notoriously harder to detect [even when the copies are identical, for example see Benson (18) for the 101 bp repeats undetected in Hellman et al. (19), a paper on the role of tandem repeats as hot spots for recombination]. Given the importance of known and potential biological roles for tandem repeats and their usefulness in other biological studies, it seemed essential to us to develop an efficient and sensitive algorithm for detecting these repeats so that they may receive further study.
A number of algorithms already exist which either directly or indirectly detect tandem repeats. All suffer from significant limitations. One group of algorithms is based on computing alignment matrices (20–22). Their primary limitation is excessive running time. The best algorithm in this group (22) has time complexity O[n2 polylog(n)] for a sequence of length n and would not be useful for sequences much longer than several thousand bases. (In this paper we report on our analysis of sequences up to 700 kb in length.)
Another group of algorithms finds tandem repeats indirectly using methods from the field of data compression. An algorithm by Milosavljevic and Jurka (23) detects 'simple sequences', i.e. mixtures of fragments that occur elsewhere. Simple sequences may or may not contain tandem repeats and this algorithm makes no attempt to deduce a repeated pattern. An algorithm by Rivals et al. (24) bases the compression on the presence of small preselected patterns (all those of size 1–3) and is not readily generalized to longer patterns for which there is an algorithmic need. To their credit, both of these methods provide a measure of statistical significance based on the amount of compression.
Another collection of algorithms aim more directly at finding tandem repeats. Of these, one exact algorithm (25) is limited by its definition of approximate patterns, requiring that two copies differ either by k or fewer substitutions (Hamming distance) or by k or fewer substitutions and indels (unit cost edit distance). Besides treating substitutions and indels as equals, the requirement for a fixed number of differences rather than a percentage difference is unsatisfactory. Any fixed number of differences suitable for small patterns (say five differences for patterns of size 20) would be unreasonably restrictive for larger patterns (five differences for patterns of size 100). Conversely, any fixed number for large patterns would allow too much variability in small patterns. A heuristic algorithm by Karlin et al. (26) is similarly hampered by the use of matching blocks separated by error blocks of fixed size. The remaining two algorithms in this group require input from the user which limits their usefulness. An earlier heuristic algorithm by Benson (27) finds tandem repeats only if they have a pattern size which is specified in advance. An exact algorithm by Myers and Sagot (28) (limited to patterns with size of at most 40 bases) requires that the approximate pattern size and a range for the number of copies be specified.
The algorithm (29) presented in this paper is designed to overcome many of the aforementioned limitations: (i) it uses the method of k-tuple matching to avoid the need for full scale alignment matrix computations; (ii) it requires no a priori knowledge of the pattern, pattern size or number of copies; (iii) there are no restrictions on the size of the repeats that can be detected; (iv) it uses percentage differences between adjacent copies and treats substitutions and indels separately; (v) it determines a consensus pattern for the smallest repetitive unit in the tandem repeat. The program has already been used as a preprocessor in a new alignment algorithm where tandem duplication augments the standard mutation set of insertion, deletion and substitution (18).
A number of ideas incorporated into this new algorithm have been utilized in earlier homology detection programs (30,31), yet the goals and methods differ. Instead of looking for highest scoring homologous regions, the algorithm looks for tandem repeats which are often hidden in larger homologous regions or which may fall well below the level of significance required for other programs to report a match. The detection criteria are based on a stochastic model of tandem repeats specified by percent identity and frequency of insertions and deletions, rather than some minimal alignment score. Finally, the program aligns repeat copies against a consensus sequence, revealing patterns of common mutations. These patterns yield insight into the history of duplications that produced the tandem repeat, thus providing a potentially valuable tool for phylogenetic research.
The remainder of this paper is organized as follows. In Methods we present a probabilistic model of tandem repeats, an algorithm overview and the set of criteria that guide the recognition process. In the Discussion we present our analysis of the frataxin (Friedreich's ataxia) gene sequence, the human b T cell receptor locus and two yeast chromosomes. Finally, in the Conclusion we describe directions for future research.
Probabilistic model of tandem repeats
We model alignment of two tandem copies of a pattern of length n by a sequence of n-independent Bernoulli trials (coin tosses). The probability of success, P (heads), which we also call pM or matching probability, represents the average percent identity between the copies. Each head in the Bernoulli sequence is interpreted as a match between aligned nucleotides. Each tail is a mismatch, insertion or deletion. A second probability, pI or indel probability, specifies the average percentage of insertions and deletions between the copies. Figure 1 illustrates the underlying idea for the model.
While Figure 1 is an interpretation of a particular alignment as a Bernoulli sequence, we are more generally interested in the distribution of Bernoulli sequences and the properties of alignments that they represent when dealing with a specific pair (pM, pI), for example (pM = 0.80, pI = 0.10). Note that these conservation parameters serve as a type of extremal bound, i.e. as a quantitative description of the most divergent copies we hope to detect.
Program outline
Our program has detection and analysis components. The detection component uses a set of statistically based criteria to find candidate tandem repeats. The analysis component attempts to produce an alignment for each candidate and if successful gathers a number of statistics about the alignment (percent identity, percent indels) and the nucleotide sequence (composition, entropy measure).
Detection component. We assume that adjacent copies of any pattern will contain some matching characters in corresponding positions. Just how many matches and how the distance between those matches should vary depend on the fixed values of pM and pI. In the next section, we develop the statistical criteria to answer these questions. Here, we describe how the matches are detected.
The algorithm looks for matching nucleotides separated by a common distance d, which is not specified in advance. For reasons of efficiency it looks for runs of k matches, which we call k-tuple matches. A k-tuple is a window of k consecutive characters from the nucleotide sequence. Matching k-tuples are two windows with identical contents and if aligned in the Bernoulli model would produce a run of k heads. Because we limit ourselves to k-tuple matches, we will not detect all matching characters. For example, if k = 6 and two windows contain TCATGT and TCTTGT we will not know that there are 5 matching characters because the window contents are not identical. Put in terms of the Bernoulli model, the aligned windows would be represented by the sequence HHTHHH, which is not a run of 6 heads.
The basic operation of the detection component is illustrated in Figure 2. Let S be a nucleotide sequence. We select a small integer k for the tuple or window size (k = 5 for example) and keep a list of all possible k length strings (there are 4k for the DNA alphabet A,C,G,T) which we call the probes. By sliding the window across the sequence, we determine the probe at each position i in S. For each probe p, we maintain a history list Hp of the positions at which p occurs.
When a position i is added to Hp, we scan Hp for all earlier occurrences of p. Let one earlier occurrence be at j. Since i and j are the indices of matching k-tuples, the distance d = i − j is a possible pattern size for a tandem repeat. For the criteria tests, we need information about other k-tuple matches at the same distance d where the leading tuple occurs in the sequence between j and i. A distance list Dd stores this information. It can be thought of as a sliding window of length d which keeps track of the positions of matches and their total.
List Dd is updated every time a match at distance d is detected. Position i of the match is stored on the list and the total is increased. The right end of the window is set to i and matches that occurred before j = i − d are dropped from the list and subtracted from the total. Lists for other nearby distances are also updated at this time (Random Walk Distribution in the next section), but only to reset their right ends to i and remove matches that have been passed by the advancing windows. Information in the updated distance lists is used for the sum of heads and apparent size criteria tests as described in the next section. If both tests are passed, the program moves on to the analysis component.
Statistical criteria. The statistical criteria are based on runs of heads in Bernoulli sequences, corresponding to matches detected with the k-tuples and stored in the distance lists. The criteria are based on four distributions which depend upon: (i) the pattern length, d; (ii) the matching probability, pM; (iii) the indel probability, pI; (iv) the tuple size, k. For each distribution, we either calculate it with a formula or estimate it using simulation. Then, we select a cut-off value that serves as our criterion. Below we describe the distributions and criteria in more detail.
Sum of heads distribution. This distribution indicates how many matches are required. Let the random variable Rd,k,pM = the total number of heads in head runs of length k or longer in an iid Bernoulli sequence of length d with success probability pM. The distribution of Rd,k,pM is well approximated by the normal distribution and we have previously shown that its exact mean and variance can be calculated in constant time (32). For the sum of heads criterion, we use the normal distribution to determine the largest number, x, such that 95% of the time Rd,k,pM ≥ x. For example, if pM = 0.75, k = 5 and d = 100, then the criterion is 26. Put another way, if a pattern has length 100 and aligned copies are expected to match in 75 positions, then by counting only matches that fill a window of length 5, we expect to count at least 26 matches 95% of the time.
Random walk distribution. This distribution describes how distances between matches may vary due to indels. Because indels change the distance between matching k-tuples (Fig. 3), there will be situations where the pattern has size d, yet the distance between matching k-tuples is d ± 1, d ± 2, etc. In order to test the sum of heads criterion, we count the matches in Dd ± Δd, for Δd = 0, 1, …, Δdmax for some Δdmax. In our model, indels are single nucleotide events occurring with probability pI. Insertions and deletions are considered equally likely and we treat the distance change as a problem of random walks. Let the random variable Wd,pI = the maximum displacement from the origin of a one-dimensional random walk with expected number of steps equal to pI·d. It can be shown (33) that 95% of the time, Wd,pI ranges between . We set Δdmax = . For ⌋example if pI = 0.1 and d = 100, then Δdmax = 7.
Apparent size distribution. This distribution is used to distinguish between tandem repeats and non-tandem direct repeats (Fig. 4). For tandem repeats, the leading tuples in matching k-tuples will be distributed throughout the interval from j to i, whereas for non-tandem repeats, they should be concentrated on the right side of the interval near i. Let the random variable Sd,k,pM = the distance between the first and last run of k heads in an iid Bernoulli sequence of length d with success probability pM. Sd,k,pM is the apparent size of the repeat when using k-tuples to find the matches and will usually be shorter than the pattern size d. We estimate the distribution of Sd,k,pM by simulation because we make it conditional on first meeting the sum of heads criterion. For given d, k and pM, random Bernoulli sequences are generated using pM. For every sequence that meets or exceeds the sum of heads criteria, the distance between the first and last run of heads of length k or larger is recorded. From the distribution, we determine the maximum number y such that 95% of the time Sd,k,pM > y. We use y as our apparent size criterion. For example, if pM = 0.75, k = 5 and d = 100, then the criterion is 56. In order to test the apparent size criterion, we compute the distance between the first and last tuple on list Dd. If the distance between the tuples is smaller than the criterion, we assume the repeat is not tandem or that we have not yet seen enough of it to be convinced.
Waiting time distribution. This distribution is used to pick tuple sizes. Tuple size has a significant inverse effect on the running time of the program because increasing tuple size causes an exponential decrease in the expected number of tuple matches. If the nucleotides occur with equal frequency, then increasing the tuple size by Δk increases the average distance between randomly matching tuples by a factor of 4Δk. If k = 5, the average distance between random matches is ∼1 kb, but if k = 7, the average distance is ∼16 kb. Thus, by using a larger tuple size, we keep the history lists short. On the other hand, increasing the tuple size decreases the chance of noticing approximate copies because they may not contain a long, unbroken run of matches. Let the random variable Tk,pM = the number of iid Bernoulli trials with success probability pM until the first occurrence of a run of k successes. Tk,pM follows the geometric distribution of order k. If we let p = pM and q = 1 − p then the exact probability P(Tk,pM = x) for x ≥ 0 is given by the recursive formula (34)Table 1 shows the range of tuple sizes and the corresponding pattern sizes currently used by the program.
Analysis component. If the information in the distance list passes the criteria tests, a candidate pattern consisting of positions j + 1 … i is selected from the nucleotide sequence and aligned with the surrounding sequence using wraparound dynamic programming (WDP) (35,36). If at least two copies of the pattern are aligned with the sequence, the tandem repeat is reported. Several implementation details of the analysis component are described below.
Multiple reporting of repeat at different pattern sizes. When a single tandem repeat contains many copies, several pattern sizes are possible. For example, if the basic pattern size is 26, then the repeat may be reported at sizes 26, 52, 78, etc. We limit this redundancy in the output to, at most, three pattern sizes. Note that we do not automatically limit the output to the smallest period size because a much better alignment may come from a larger size (for example Table 5, indices 410172–410459).
Narrow band alignment. Alignments are the program's most time intensive calculations. To decrease running time, we limit WDP calculations to a narrow diagonal band in the alignment matrix for patterns larger than 20 characters. In accordance with the random walk results, the band radius is Δdmax. The band is periodically recentered around a run of matches in the current best alignment.
Consensus pattern and period size. An initial candidate pattern P is drawn from the sequence, but this is usually not the best pattern to align with the tandem repeat. To improve the alignment, we determine a consensus pattern by majority rule from the alignment of the copies with P. The consensus is used to realign the sequence and this final alignment is reported in the output. Period size is defined as the most common matching distance between corresponding characters in the alignment and may not be identical to consensus size.
Program usage and output
Input to the program consists of a sequence file and the following parameters: (i) alignment weights for match, mismatch and indels; (ii) pM and pI; (iii) a minimum size for patterns to report; (iv) a minimum alignment score to report. We have developed a web based interface for the program. Using an HTML form at c3.biomath.mssm.edu/trf.html, the user provides an input DNA sequence file. Defaults can be used for the remaining parameters. After program execution, two files are returned. The first is a summary table describing the location and statistical properties of the tandem repeats found. The second contains the alignment of each repeat with its consensus sequence. The files are linked so that selecting an entry from the table opens a second browser window which contains the proper alignment. The summary table includes the following information: (i) indices of the repeat in the sequence; (ii) period size; (iii) number of copies aligned with the consensus pattern; (iv) size of the consensus pattern (may differ from the period size); (v) percent of matches between adjacent copies overall; (vi) percent of indels between adjacent copies overall; (vii) alignment score; (viii) percent composition for each of the four nucleotides; (ix) entropy measure based on percent composition.
To demonstrate the capabilities of our program, we used it to analyze four sequences, the human frataxin gene sequence (Friedreich's ataxia) (5), the human β T cell receptor locus sequence (37) and two yeast chromosomes (I and VIII). [The frataxin gene sequence and the human β T cell receptor sequences were obtained from GenBank. The yeast chromosomes sequences were obtained via ftp from ftp.ebi.ac.uk directory pub/databases/yeast in files chri_230209.ascii and chrviii_562638.ascii. Indexing in this paper is relative to the sequences in these files. Data file accession numbers for these sequences are: frataxin gene promoter and intron 1, U43748; human T cell receptor, L36092; yeast chromosome 1, U12980, L20125, L05146, L22015, L28920; yeast chromosome 8, U11583, U11582, U11581, U10555, U10400, U10399, U00062, U00061, U10556, U00060, U00059, U10398, U10397, U00027, U00028, U00030, U00029.] In our analysis, we searched for all pattern sizes between 1 and 500 bases (the implementation's current upper size limit, to be extended in subsequent versions). We used one of two sets of alignment parameters (match, mismatch, gap), either (+2,−7,−7) or (+2,−5,−7). Only those repeats scoring at least 50 with these parameters are reported. Occasionally, the same repeat is reported at different pattern sizes. We have omitted these redundancies.
We performed two searches on each sequence, using different conservation parameter values, (pM = 0.75, pI = 0.20) and (pM = 0.80, pI = 0.10). While the first search is slower than the second, the detected repeats are nearly identical. Table 2 shows running times of the program and Tables 4–7 list the tandem repeats found.
Human frataxin gene (Friedreich's ataxia), intron 1
Friedreich's ataxia is one of the triplet repeat diseases (5). It is caused by copy number expansion of the triplet GAA in the first intron of the frataxin gene. Table 4 lists the repeats found in the sequence. Besides the triplet repeat, our program found two others which were apparently unknown, a 44 bp pattern and a 14 bp pattern. Figure 5 shows the program's alignment of the 44 bp repeat.
Human β T cell receptor locus sequence
This sequence (37) contains a family of immune recognition coding elements, the T cell receptor variable, diversity, joining and constant gene segments. It was selected for its size and because many tandem repeats within the sequence had already been identified. Table 5 lists the new repeats we found. Of the 83 repeats that we found, 38 were previously annotated and most of those were for patterns of size 5 or smaller. We missed 6 annotated repeats: 4 dinucleotide repeats and 1 tetranucleotide repeat (alignment scores were below our cut-off) and 1 repeat with period size 10 567 bases (beyond the current implementation's pattern upper size limit). Of the 45 unannotated repeats, 13 have short patterns (2–6 bp) and may be polymorphic and thus useful for linkage analysis. Six unannotated repeats have large pattern sizes (116, 65, 52, 49, 34 and 30 bp). The 116 base pattern is also reported at size 39 with a lower scoring alignment. The annotated 60 base pattern repeat (indices 12596–13266) is indicative of the program's ability to find repeats with substantial amounts of mutation between adjacent copies (74% matching characters and 7% indels overall).
Yeast chromosomes
Tables 6 and 7 list the tandem repeats found for the yeast sequences. Of special interest are the clusters of tandem repeats which show up repeatedly at the ends of the chromosomes, suggesting recent swapping of the ends. Chromosome 8, in particular, has two different clusters on its right end.
The (27, 21, 48, 15, 135) cluster
The FLO1 gene and its paralogous pseudogenes in chromosomes 1 and 8 contain a cluster of 5 tandem repeats with pattern sizes 27, 21, 48, 15 and 135. We designate these clusters C1 and C2 (adjacent on the left end of chromosome 1), C3 (right end, opposite strand) and C4 (right end of chromosome 8). The 27, 48 and 135 base patterns are not reported in every cluster in Tables 6 and 7. Subsequent analysis of the surrounding sequences, however, revealed that every pattern is present but not necessarily as two or more copies (Table 3). For each pattern size, the number of copies varies among the four clusters. More specifically, no cluster is identical in its copy number to any other cluster. This implies that duplication or excision events (deletion of copies) have occurred since the separate clusters were incorporated into the chromosomes. The sequences around these clusters also reveal close homology. For example, C3 and C4 are nearly identical over 18 000 bases and C2 and C3 display homology over 15 000 bases.
The (13, 10, 36) cluster
A cluster of 3 tandem repeats with pattern sizes 13, 10 and 36 bases appears on both ends of chromosome 8 (Table 7). The 36 bp pattern also appears on the left end (low index numbers) of chromosome 6 (not shown). For the 36 bp pattern, each occurrence has a different copy number. The 10 and 13 bp patterns are identical in their occurrences. Surrounding sequences comprising 4200 bases are nearly identical for these three clusters.
In this paper, we have presented a new algorithm for finding tandem repeats in DNA sequences without the need to specify either the pattern or pattern size. The algorithm is based on the detection of k-tuple matches. It uses a probabilisitic model of tandem repeats and a collection of statistical criteria based on that model. We have demonstrated the speed and utility of the algorithm by analyzing four sequences ranging in size up to 700 kb. Several avenues for future research are raised by this work, including methods to estimate statistical significance for tandem repeats and algorithms to determine plausible mutational histories.
Statistical issues
We have yet to develop a good statistical significance measure for tandem repeats. For now, we use a cut-off alignment score based on simulations with random sequences. Difficulties include the local variation in nucleotide content in real sequences, which is decidedly non-random, and the problem of accounting for copy number as well as total repeat length. Estimates of significance developed in Benson and Waterman (27) are too high in this application because they apply to tandem repeats of one pattern size only, rather than the range of sizes considered here.
Mutational history
Analyzing the mutational history of tandem repeats requires utilizing the pattern of mutations among adjacent copies to describe the interwoven progression of substitutions, indels and duplication/excision events leading from a single copy of the pattern to the present day sequence. Such histories can suggest how the boundaries and size of the duplication unit vary and may reveal details about the duplication mechanism.
The author would like to thank Xiaoping Su for his help in analyzing the sum of heads criterion, Astrid Jervis for her help in simulating many of the statistical measures and examining the program output and Lan Dong for her help with some of the programing and examining the output. Thanks also to Mike Waterman, Richard Arratia and Rolf Backofen for helpful discussions. This work was partially supported by NSF grant CCR-9623532.


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January as always marks a yearly Societies Convention for anything photography. I visited the convention to see what's new and learn something new as well. If you've never been to the event, it's a photography gatherng where most big names in the industry appear, companies like Fujifilm, Canon, Sony, etc. They present their products and
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The Societies Photography Convention
The end of the year comes close and after that there comes January. Yes, I know you know that 😉 What I want to say is that when January comes, in central London we're going to have one of the biggest photography events of the year – the Societies Convention. It's one of these events


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Solid State Chemistry: Compounds
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Solid State Chemistry: Compounds by A. K. Cheetham
Book DescriptionSolid State Chemistry meets the need for an authoritative account of the properties of inorganic solids and the methods for studying them, written at a level suitable for final year undergraduates studying the subject as a special topic or for first-year graduate students embarking on research in the field. This second volume deals with the electronic structure and bonding in solids, and then focuses on several important classes of inorganic compounds.
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