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Hello everyone, Flight Volunteer needed for our cat Morgana From PHUKET to ITALY.
If someone is flying to Italy please let me know. She's ready to fly to us!!!
leave a message to email@example.com…. Thank you
We often have adopted animals needing to travel to/from various locations around the world to their new homes and sending an animal with a passenger (rather than alone) often makes the cost of adopting an animal abroad much more affordable. For instance a dog travelling from Thailand to USA can cost as little as $200.
Some airlines have very cheap rates for dogs travelling "accompanied" (i.e. with a passenger) and we are always looking for passengers travelling with these airlines & willing to accompany an animal on their flight. Learn more about our Flight Volunteer program and watch our Video. If you're travelling abroad, please register your flight with us. It may be just the flight we're looking for!
You could help an animal reach it's new home, it's easy & very rewarding!
What it takes to be an animal rescue flight volunteer | Travel News
Hello everyone, Flight Volunteer needed for our cat Morgana From PHUKET to ITALY.
If someone is flying to Italy please let me know. She's ready to fly to us!!!
leave a message to email@example.com…. Thank you
Hello Am intrested in doggy handling flight volenteerting is there some imformation of starting.
I need 2 Flight Volunteer from Beijing to Los angeles anytime in the next 2 months – My friend will get the 4 puppies at the airport.
I hope someone can help!
FLIGHT VOLUNTEERS WANTED by our Dogs & cats rescue group! Are you travelling from China to U.S.A. in the coming month? looking for 2 flight volunteers to escort Two samoyed Two Huskies from Beijing to LosAngeles all paid and arranged. PLS 🙏🙏🙏
Desperately looking for a flight volunteer to escort a doggie from Jordan Middle East to Canada or USA all paid and arranged please help
Desperately need a flight volunteer in June from Korea to Canada (Toronto). Earliest possible day is June 17th. The puppy's owner has a terminal illness and no one will be able to take care of the dog.
Please help us give her a loving home! Thank you!
After 17 Hours in a Crate, This Neglected Dog is About to Meet Her New Family | Cute Brigade
I need a Flight Volunteer from Bangkok Thailand to Toronto, Canada anytime after March 6th – I will travel to the US or other cities in Canada to get my newly beloved puppy. I hope someone can help!
Taking a chance… I am desperately in need of a FV going from JAKARTA to Canada in March
I am looking for a flight volunteer ASAP from Bangkok to Toronto, Canada for 1 puppy. I will provide compensation!
Hello. This is Hannah.
I am really happy with your website.
I was looking for a flight volunteer for my dog that is in my friend's house in Houston. I moved to LA last summer from Houston so my friend adopted her since then. Now she is really busy so my dog has to be alone for a long time everyday. I need to take care of her again. Please help me. I don't know what I have to do. I will look forward to having your contact to me. Thank you soooo much.
We need a flight volunteer to accompany a dog travelling from Athens Greece to either Glasgow or Edinburgh Scotland. We are a small rescue and have a family in Scotland who want to adopt.
Hello community,
I'm looking for a flight volunteer from Shanghai to Frankfurt, Düsseldorf, Cologne or possibly other German cities. The earliest travel day is September 8, 2017.
I adopted my dog, Rain, from a rescue organisation in Shanghai. They will take care of baggage costs and there will be someone to help you at both airports.
Please contact me if you're interested.
Hi there,
I am in need of a flight volunteer and was wondering if there would be a flight available that is not being used by one of your dogs. My puppy is in Thailand and I need her to come to Canada.
Hi! Does anybody will fly from Vietnam (Ho Chi Minh or Hanoi) to any country in Europe at end of July or anytime in August? Are you willing to take a medium size dog with you(8k plus cage)??I need to bring a my dog from Vietnam to Poland. I can pick it up in any city in Europe.
Please let me know.
I am flying from Bangkok to Munich on 24.04.2017 till 09.05.2017, does anyone need a flight volunteer?
I would be very interested to register as a dog volunteer, but I need to ask, do I pay for the flight from one country to another?
I am Flying from BKK to LAX ( stop in Nrt) flight 284 on Mar 30 . I work for Delta but this is a POSITIVE ticket not standby,delta Airlines will no longer take large dogs in cargo 🙁
I could possibly take a small dog or cat?
P,ease let me know. Maybe my companion would too.
Thank you
hi donna..saw yr post from 2017 about flt vol..i am trying to help transport for BKK rescue THAI STREET PAWS RESCUE & rescue in LAX will receive dog/s…i have no def date, to be determined, so i think fairly flexible…if u still do this, i shall get all the info u need from them..i checked with res and they say DL DOES TAKE DOGS cargo so if u dont to it any more would any of yr coworkers contact me if they do…..fyi i worked PAA 30yrs, but DL didnt need my department, so sadly no more, but DL did give many years of passes, but those are funished now or i would do this myself….thank u so very much maryfran
Hello, we are in great need of flight volunteers to safely bring puppies from Teheran (Iran) to California . the 13 puppies have until the end of March 2016 to move from their temporary shelter in Iran. The rescue organization who is in charge of finding them foster homes until adoptions is Dog without borders.
We are looking for a flight voluteer by end Nov 15 or beginning ofDecember 15 from Bangkok to Zurich. First possible travel day is Nov. 28. Can anybody help us? Then please contact us. Rgds Ina
Hi, I need some volunteer to get my puppy dog chi zu from Thailand, Bankok to Finland, first possible travel day is 18.7.15. If someone is interested bring the dog to Finland, please contact me.
I will be going to Headrocks in bang saphan end of the year but it's to work. I do know the founders of k9 aid and one is a very good friend of mine. I will help you if you can wait? I won't be returning to the UK until 3-4 months tho. Pm me.
My sponsor dog is Kanan.
I could be a flight volunteer but have not saved enough money to get to Thailand from Australia.


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Reminder: There will be no classes at CrossFit St. Paul this weekend due to the gym being the host site for a CF Level 1 seminar. Minneapolis will hold it's normal class schedule. There is also an outdoor workout this morning at Merriam Park near the gym at 800am. Friends and family are welcome to come!
Bench Press:
10 – 5 – 1
AMRAP 20 Minutes:
5 R-Arm KB Snatch (53/35)
5 L-Arm KB Snatch
7 C2B Pull-Ups
Click here to view this week's upcoming programming, complete with tips and considerations to make every workout both challenging and fun!
Post thoughts and results to beyond the whiteboard.
Stay in the know with upcoming gym events and announcements. Click here to see what's going on this week.

subset: commoncrawl


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Absolutely Psychic Network Has ONLY The Best Psychics
All psychic mediums have been screened prior to hire.
Only 3 out of 100 psychic medium applicants are offered a position on the network.
Our psychics reading is 60% LESS than our competitors without compromising quality.
This video will show you to to easily interpret instantly a birth chart. The basic aspects of the astrology chart to give you a solid and basic structure.
The personality, love life, financial destiny, and personality can be seen by eyeballing
Be sure to check our other Astrology videos and articles. Enjoy!


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Karezza and Condoms [1]
Hi Everyone, I just joined as I am in need of some direction and advise to help with the start of my Karezza practice. First off, no I have not read any of the books. However, I have read every posting on this site and every other website on the net, including the blogs. Unfortunately, I still never found some answers to my questions.
The one thing I couldn't find much about is birth control. I'm married and I'm on my 11th day of reboot as of today! Last night, while in scissors position (new to us)I was just hanging outside of her vagina and being so wet I just slipped my tip in just a little by mistake. Feeling so good to both of us and being at the end of my reboot I grabbed a condom and tried inserting and just lying there with her. We really didn't feel the energy but she did like that she felt me grow inside her a little. However, as fast as I grew the faster it went down. Since she was so wet, I didn't realize that I was totally soft and even popped out, which screwed up the condom. We tried it again and the same thing happened. It only took a second to become hard again so I suggested we go traditional missionary and had no issues. I started off real slow (reframing from thrusting) and stopped a few times to try and get a connection. Since I was on top I couldn't totally relax as I didn't want to put all my weight on her. I lasted about 45min (I've always had good control) before I had to tap out or lose my reboot, if you get what I'm saying lol.
So while searching today about Karezza and condom usage I really didn't find much at all. I understand erections come and go with Karezza but how do you stop from going soft and popping out while in scissor position? And does anyone here use or have used condoms that can give me some feedback? I'm looking into women condoms this week and might try this as an alternative. A little help for a newbie Please!
- Karezza [3]


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We've been using commands like "link:www.conscious.co.uk" for years to check how big websites are. We've noticed for at least two years that the numbers it showed were not consistent with Google Webmaster Tools (aka Search Console). Google have now confirmed this.
Rumors are swirling this week that Google's link operator could soon be switched off for good, after respected internet marketer, Bill Hartzer noticed that the function had stopped working for many top sites.


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Operationalizations of the Rokkanian centre-periphery cleavage have traditionally focused on the presence of specific regional political cultures, as well as on cultural fragmentation within a country (at the aggregate level) or on proxy indicators such as town size (at the individual level). We suggest that geographical remoteness from political
centres – a key element of the centre-periphery cleavage in the Rokkanian framework – could provide a more accurate measurement of the subjective position of individuals in relationship to the cleavage. As new indicators of this concept, we introduce measures of distance between the place
of residence of a citizen and political centres at different hierarchical levels, based on road distances and travel times along traditional roads (also
accounting for differences in orography and geography among different countries and regions). We
empirically test the impact of such indicators on vote choice on the Italian and French cases. We use survey data from the 2006 ITANES and the 2002 PEF,
and information about road distances and travel times obtained through online mapping/routing services. We first assess differences between
the two countries in terms of orography and geography. We then estimate multivariate models of vote choice at the individual level, in order to te
st the following hypotheses: a) that the new indicators add significant explanatory power, compared to traditional indicators related to the
centre-periphery cleavage; b) that the new indicators have different effects on vote choice for different parties, expressing different affinities
of these parties with the cleavage.


text: So I've come to that point of the year where I utterly despise my hair. It doesn't like to cooperate around this time of the year. Probably because the humidity is so high but whatever, the point is I'm tired of it. So what does a natural do when they're sick of their hair?….get a protective style! This time I decided to try Marley twists because I like how they look so natural. *shrugs I just like kinky hair. Anyways, installation took about 5.5 hours and about 6 packs of hair were used. I've only had them for a day but so far I like them because 1) they're not heavy and 2) it looks my hair and 3) they're not….."perfect". My real twist-outs are different lengths and sizes and I like how this style mimics that. Needless to say for right now I give the Marley twists a thumbs up!


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GRAND RAPIDS — Mark Christner has been named head women's basketball coach at Calvin College.
The move is a homecoming for Christner as he is a 1999 Calvin College graduate.
A native of Big Rapids, Christner returns to Calvin after spending the previous nine years as head men's basketball coach at Waynesburg University (Pa.). Prior to serving as head men's basketball coach at Waynesburg, Christner spent eight years as an assistant coach with the Calvin men's basketball program and three years as an assistant coach with the Calvin women's basketball program.
"It is with great excitement that I welcome Mark Christner home as our new women's basketball coach," said Calvin Director of Athletics Dr. Jim Timmer Jr. "He is well-versed in the mission of our institution and he has a deep love for Calvin College. He also has a strong understanding of what it takes to produce a successful basketball program, both on and off the court. I am confident that Mark will do a tremendous job as our head women's basketball coach and our athletic department is looking forward to having him rejoin our family."
Christner is ready to get started at his alma mater. "I am extremely grateful and blessed to have this opportunity," said Christner. "I would like to personally thank Dr. Timmer and Dr. Meyer for extending this opportunity to me. They have both been wonderful to me in this process. It is a bittersweet in that I am leaving my Waynesburg family. What makes this change much easier is that I will be rejoining a family that is also very close to my heart in Calvin College. I am looking forward to joining a program with a strong tradition and a good base of players. The MIAA is a nationally-known conference for women's basketball and we have work to do to keep moving upwards. I am looking forward to the challenge."
Christner will come to Grand Rapids with his wife Sara (Plasman) Christner and son Leo (13) and daughters Elin (10) and Nora (8). His wife Sara is an alumna of both the Calvin women's basketball and Calvin softball programs.
At Waynesburg, Christner took over a men's basketball program that had posted a 2-22 record the year prior to his arrival. He led the Yellow Jackets to five double-digit win campaigns including an 18-11 record during the 2014-15 season that saw Waynesburg reached the President's Athletics Conference Tournament Championship game. This past academic year, Christner has also served as Waynesburg's Assistant Athletic Director in charge of compliance and player and coach development.
During his eight years (2002-2010) as an assistant men's basketball coach and head men's junior varsity coach at Calvin, Christner helped lead the Knights to four berths in the NCAA Division III national tournament. During his time on the bench, Calvin posted an impressive 158-73 record and won three Michigan Intercollegiate Athletic Association (MIAA) regular season titles. Over that same stretch, the Knights won three MIAA tournament titles and advanced all the way to the NCAA Division III National Semifinals in 2005.
Prior to working with the men's team, Christner broke in as a coach at Calvin with the women's basketball team from 1999 to 2002. In 2000, the Calvin women made it all the way to the NCAA Division III Tournament Round of 16
Christner earned his Bachelor of Arts degree in 1999 from Calvin, where he majored in history and minored in physical education with an emphasis in coaching. He went on to earn a Master of Arts degree in physical education with a pedagogy emphasis in 2005 from Western Michigan University. At Calvin, he played two years on the Calvin junior varsity men's basketball team and one year on the varsity.
He is also an experienced teacher. Christner was a Health, Physical Education, Recreation, Dance, & Sport (HPERDS) instructor at Calvin from 2006 until he left the school and was an adjunct instructor in the same program from 2004 to 2006. He also spent four years (2000-2004) as a social studies teacher at both the Creston Christian School and the Holy Spirit School in Grand Rapids.


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Project Description
KAE undertook the tender mechanical and electrical services design on behalf of our client for this $97M (circa.) project. In addition KAE provided medical gases and hydraulic services via specialist sub-consultants for this project.
This hospital comprised all major departments including Accident & Emergency, Operating Theatres, Pathology, Paediatrics/Maternity, Mortuary, Mental Health, Pharmacy etc.
One of the main features of this project was emphasis on innovation and technology. KAE expertise in conjunction with the project team, maximised our clients bid for this project incorporating many innovations.
KAE were able to provided Full detailed design of the services to enable accurate market pricing to be achieved by our client. This also 'took the guesswork out of' what was to be delivered to the Health department and from tendering contractors.


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This Friday, Vienna will be the host of the first event on my book tour. A preliminary schedule is posted below, more dates will be added as they are confirmed.
Vienna, May 18, at Capitalbank, Palais Esterházy
Zurich, May 23, organized by Bitcoin Switzerland Association, at the Volkshaus.
Munich, May 29 at MaibornWolff GmbH
Paris, May 30, at Accenture
Boston, MA, June 5, at Fidelity (open only to Fidelity employees)
New York, NY, June 12, Columbia University
Charlotte, NC, June 13, Wework Stonewall Station
Miami, FL, June 15. 1 Hotel South Beach.
Calgary, AB, July 9, at the Bitcoin Rodeo conference
Montreal, QC, July 10, Keynote speech at Startupfest
Dallas, TX, July 14-15, BitcoinBlockBoom Conference
Toronto, ON, July 23, Spaces, 180 John St
Chicago, IL, August 11, mHUB, 985 W Chicago Avenue


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Delve deep into the passionate history of one of Italy's most influential families: the Medicis. Discover their secrets and their artistic legacy on this walking tour of Florence. You'll also enjoy a food tasting of typical Tuscan delicacies!
Medici Florence Tour Itinerary
This guided walking tour of the Florence of the Medici family will take you to some of the Italian city's most important monuments, revealing the history of the richest family in Italy and their huge impact on the art and architecture of the region. You'll visit the Palazzo Pitti, a majestic Renaissance palace. It was bought by the Medicis in 1549 and was their chief place of residence for 200 years.
Inside the Pitti Palace, the Medici family would hold extravagant parties and banquets as a display of their power and wealth. Did you know that this family governed Florence for 350 years? Your expert guide will explain their history and reveal curious facts surrounding them while you contemplate the famous Vasari Corridor, a covered passageway that connects the palace with the Palazzo Vecchio, commissioned by the Duke Cosimo I de' Medici in 1565 so that he could pass freely between the palaces without having to be seen. It passes over the River Arno, built on top of the shops on Ponte Vecchio, and even goes through the Santa Felicita Church, so that the Medicis could attend mass without mixing with the public.
The famous dynasty left their imprint on practically every branch of society during their time. Amongst the family members, there were three popes, two queens, various military leaders and a number of politicians, like Lorenzo "The Magnificent". This ruler of Republic of Florence was a true patron of Renaissance arts, sponsoring artists including Buonarroti, da Vinci and Botticelli... You'll hear lots more about "the Magnificent" as you pass the impressive Palazzo Medici.
Tuscan Street Food Tasting
Not only will you experience the history of Tuscany and its beautiful capital on this tour, but you'll also have the opportunity to delight your taste buds with its cuisine. Before finishing off your guided route around the city centre at around 2:45 pm, you'll make a total of three stops at different street food stalls in the old quarter. At each one, you'll try a speciality of local gastronomy.
Sample a selection of salumi, a tasting plate of Italian cold cut meats; coccoli or Tuscan fried bread dough, a popular snack of Florentines for many years; and gelato, homemade ice cream. For the perfect accompaniment, enjoy a glass of Gottino, a wine from the Tuscan region of Chianti.
|Children between 6 and 17 years old
|Children under 6 years old
|English guided tour
English guided tour
AdultsUS$ 38.8
Children between 6 and 17 years oldUS$ 21
Children under 6 years oldFree
More Information
2 hours.
The tour is exclusively in English.
English speaking guide with expert knowledge of Florence history.
Tuscan food tasting (salumi, coccoli and gelato).
Glass of Chianti wine.
When to book?
Book as soon as possible to guarantee availability, especially during public holidays and festivities.
You can book up until the same day (11:45 AM local time) if there are still places available.
Once your booking has been confirmed, you will receive an email containing your booking voucher. Please print it out or download on your smartphone/tablet to show on the day of the activity.
Frequently asked questions
Q - How to book?
A - To reserve the activity, choose the date and complete the form on this page. You will receive your confirmation immediately.
If you still have more questions, check out our section on frequently asked questions. If you need help to book an activity or have any enquiries, please contact us.
No (not suitable for people with reduced mobility).
Meeting point
21 Via Camillo Cavour (red).


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Hotels in Bentfeld, Germany
Search & Compare Bentfeld Hotels
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Best hotels in Bentfeld
What's Bentfeld like?
If you're looking for a place to get away, look no further than Bentfeld. Whether you're planning to stay for a night or for the week, the area around Bentfeld has accommodations to fit every need. Search for hotels in Bentfeld with Hotels.com by checking our online map. Our map displays the areas and neighborhoods around all Bentfeld hotels so you can see how close you are from landmarks and attractions, and then refine your search within the larger area. The best Bentfeld hotel deals are here with our lowest price guarantee.
What types of hotels are available in Bentfeld?
We have Bentfeld accommodations with prices starting at CAD 42. Choose one of our 380 deals and get discounts of up to 20%.
Below are the number of accommodations by star rating in Bentfeld and the surrounding area:
- • 4 5-star accommodations from CAD 119 per night
- • 62 4-star accommodations from CAD 97 per night
- • 127 3-star accommodations from CAD 58 per night
- • 6 2-star accommodations from CAD 42 per night
How to Get to Bentfeld
What is the closest airport to Bentfeld?
- • Paderborn (PAD-Paderborn - Lippstadt), 9.3 mi (14.9 km) from central Bentfeld
Things to See and Do in Bentfeld
What is there to see near Bentfeld:
- • Neuhaus Castle (3.7 mi/5.9 km from the city center)
- • Adam and Eve House (5.7 mi/9.2 km from the city center)
- • Paderborn Cathedral (5.8 mi/9.3 km from the city center)
- • University of Paderborn (6.7 mi/10.8 km from the city center)
- • Salt Graduation Tower (5.2 mi/8.4 km from the city center)
What is there to do near Bentfeld:
- • German Tractor and Model Car Museum (6.1 mi/9.9 km from the city center)
- • Paderborner Land Golf Club (2.5 mi/4.1 km from the city center)
- • Heinz Nixdorf MuseumsForum (4.8 mi/7.6 km from the city center)
- • Imperial Palace Museum (5.7 mi/9.2 km from the city center)
- • Schloss Neuhaus Open Air Theatre (3.5 mi/5.6 km from the city center)
When is the best time to visit Bentfeld?
- • Hottest months: August, July, June, September (average 69°F)
- • Coldest months: January, February, December, March (average 30°F)
- • Rainiest months: July, June, August, and May (average 3.06 inches of rainfall)


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Twins Penny and Peyton are celebrating their birthday at a very special place, Mr. Chapman's Pet Pal Emporium, where each guest is matched with their perfect pet pal. There are all sorts of fun activities for the twins and their guests to experience at the Pet Pal Emporium, all under the supervision of Mr. Chapman. All the children are excited to see the animals, but Peyton wonders if he will receive a perfect pet pal. Will he or won't he?
When I first received this book, the first thing I noticed was the sturdiness of it. It seems like an odd thing to take note of in a book, but it really impressed me that it was so sturdily bound that it would last for a long time, so I wanted to make sure to share that with readers.
Next, I noticed that beautiful illustrations on the pages, along with the extra challenges for readers to find an assortment of hidden details on the pages. Very helpful when simultaneously reading with children of different ages! The little ones can look at the pictures and find the hidden animals, while older ones can really focus on the story!
Finally, when reading the story, I enjoyed the storyline. The alliteration was fun to read and I really liked the way the authors included just enough characters to demonstrate the five love languages in action, without making it too confusing for younger readers to keep track of all the people. I had already read The 5 Love Languages of Children and The 5 Love Languages: The Secret to Love That Lasts, so I was familiar with them, but it helped me to assess my children's love languages. I think the questions at the end were also very helpful in discussing the different love languages with my children.
I would highly recommend this book for anyone with small children. It is a beautiful book, with a lovely story. I read it out loud to my multi-age children and they all said they would recommend it, too!
I received this book from Moody Publishers in exchange for my honest review. All opinions are my own.
Related articles
- Book Review: A Perfect Pet for Peyton (schelastic.wordpress.com)
- Book Review: A Perfect Pet For Peyton (granolarevival.com)
- What's Your Love Language? (tulletales.com)


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Quickly adjust these stackable stools to the perfect height in seconds!
Portable outdoor balance beams (single or a set of 3) can be configured in a variety of ways to fit your space!
Cross the pond without going ker-plunk!
Straight and curved 4"W steel balance beams are perfect for teaching balance and dexterity skills.
Build progressive balance skills for all ages!
A natural, ergonomic up-and-down sensory experience on an outdoor balance beam.
Economical 14" dia playground balance pods are perfect for follow-the-leader and imaginative play!
Hop slow or walk fast—playground balance small steppers are perfect for teaching balance skills!
Children hop, skip, and jump to advance agility and balance skills on wooden playground tree steppers!
Versatile, durable discs will keep kids stepping for years!
Plastic tactile beam for kids provides sensory stimulation.
Create challenging courses to develop spatial perception and movement skills.
Very high-quality balance set systems for children offers endless balance challenges!
A perfect starter set for climbing up, over, through, and down.
Bountiful collection of hills and slopes becomes waves and steps when flipped over.
Large set jumpstarts your collection.
Get kids climbing here, there, and everywhere!
Hills and slopes become waves and steps when flipped over!
The most complete gross motor play set we offer!
Add a fun stepping challenge to playgrounds with these real wood slices!


text: Thank you for your interest in our Small Business Loan Program. We look forward to working with you to grow your Newark based business. The application for a loan can be found below. If you have questions or comments please call Lexie Demirali at 973-273-1040. Thank you for your participation in Newark's revitalization.


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Marquetry with a knife – Workshop, 18 March 2018
For the March Scroll Saw and Marquetry SIG meeting, Robin Cromer and Don Rowland led an informative and interesting day long workshop on marquetry with a knife.
We started with a discussion of perspective and which pieces to cut first – always start at the back of the picture. Types of knives and blades were discussed and covered in a handout. How to cut wood veneer with a knife was then covered – a sharp blade and multiple cuts are essential.
Robin's method of marquetry is to cut a window in a background piece of veneer, and use the window to position and mark the fill piece, which is then cut out and fitted. One of the big advantages of using the window technique is that you can see the colour and grain of the fill piece and make sure it is oriented correctly before you start cutting it. Robin then demonstrated cutting out some practice shapes. We all tried the shapes, and it didn't take long to realise that it is going to take some practice to get to the level of artistry that Robin regularly achieves.
Our project for the day was a picture of gum leaves, suitable for use in a box lid. We worked on our project between lectures and demonstrations. Robin had a completed piece as an example, which he used to demonstrate glueing the picture and a backing piece to a board. Robin and Don showed us pictures and discussed their history of doing marquetry, and Don introduced some parquetry techniques and pieces. We also covered techniques for book-matching veneer and its use for effective design of marquetry pieces.
None of us managed to complete our gum leaf project but we came away with the knowledge to do that and enough materials to do a few more projects, with the hope that more marquetry pieces will be entered in the Guild's show this year.
Mary Jean Vickers


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Purpose: Polymorphisms in the genes SRD5A1 and SRD5A2 encoding androgen biosynthetic 5α-reductase enzymes have been associated with an altered risk of biochemical recurrence after radical prostatectomy in localized prostate cancer.
Experimental Design: To gain potential insights into SRD5A biologic effects, we examined the relationship between SRD5A prognostic markers and endogenous sex-steroid levels measured by mass spectrometry in plasma samples and corresponding prostatic tissues of patients with prostate cancer.
Results: We report that five of the seven SRD5A markers differentially affect sex-steroid profiles of dihydrotestosterone and its metabolites in both the circulation and prostatic tissues of patients with prostate cancer. Remarkably, a 32% increase in intraprostatic testosterone levels was observed in the presence of the high-risk SRD5A rs2208532 polymorphism. Moreover, SRD5A2 markers were associated predominantly with circulating levels of inactive glucuronides. Indeed, the rs12470143 SRD5A2 protective allele was associated with high circulating androstane-3α, 17β-diol-17-glucuronide (3α-diol-17G) levels as opposed to lower levels of both 3α-diol-17G and androsterone-glucuronide observed with the rs2208532 SRD5A2 risk allele. Moreover, SRD5A2 rs676033 and rs523349 (V89L) risk variants, in strong linkage disequilibrium, were associated with higher circulating levels of 3α-diol-3G. The SRD5A2 rs676033 variant further correlated with enhanced intraprostatic exposure to 5α-reduced steroids (dihydrotestosterone and its metabolite 3β-diol). Similarly, the SRD5A1 rs166050C risk variant was associated with greater prostatic exposure to androsterone, whereas no association was noted with circulating steroids.
Conclusions: Our data support the association of 5α-reductase germline polymorphisms with the hormonal milieu in patients with prostate cancer. Further studies are needed to evaluate if these variants influence 5α-reductase inhibitor efficacy. Clin Cancer Res; 20(3); 576–84. ©2013 AACR.
Translational Relevance
Prostate cancer is a heterogeneous disease at the molecular and clinical levels requiring an individualized approach to patient care. The importance of androgen in cancer initiation and progression is clearly established at all disease stages. Moreover, 5α-reductase inhibitors (5-ARI) have shown potential clinical efficacy as chemopreventive medications. Likewise, SRD5A polymorphisms were recently associated with altered risk of biochemical recurrence in localized prostate cancer disease. To gain insights into SRD5A biologic effects, we examined the relationship between SRD5A prognostic markers and endogenous sex-steroid levels measured by gold-standard mass spectrometry methods in plasma and corresponding prostatic tissues of patients with prostate cancer. Our findings sustain the significance of common inherited SRD5A polymorphisms on the modulation of the androgenic milieu of patients with cancer. The utility of understanding the impact of SRD5A germline determinants on androgen exposure is that it could potentially be used to identify subgroups of patients, with a particular androgen microenvironment profile, that would most benefit from 5-ARI. Therefore, protective and high-risk germline SRD5A alleles associated with changes in hormone levels may lead to more personalized approaches to refining 5-ARI therapy, especially early in disease course.
Prostate cancer is the most frequent malignancy in men and the second leading cause of cancer death in Western countries (1). It is well established that androgens play a central role in prostate cancer progression even until it reaches advanced stages. Indeed, the conversion of testosterone (T) by 5α-reductase (5-AR) enzymes (types 1 and 2) leads to dihydrotestosterone (DHT), the most potent androgen receptor agonist in prostate cells. Under normal physiologic conditions, SRD5A2, which encodes a 5-AR, is preferentially expressed over SRD5A1 in the prostate (2, 3). In prostate cancer cells, however, the balance in expression of these genes shifts toward predominant expression of SRD5A1 (3, 4), supporting a role for both enzymes in DHT bioavailability and carcinogenesis. In fact, 5-AR enzymes represent attractive targets for preventing prostate cancer development. In that context, the importance of androgens in early cancer initiation is emphasized by the fact that finasteride, a 5-AR type 2 inhibitor, and dutasteride, a dual 5-AR inhibitor targeting both 5-AR type 1 and type 2 enzymes, have been shown to reduce by almost 23% the risk of prostate cancer incidence (5, 6). More recently, the REDEEM trial conducted with patients with low-risk prostate cancer showed that dutasteride also reduced by 10% the likelihood of cancer progression (7).
However, prostate cancer is clearly a heterogeneous disease, and prediction of response to treatment and progression remains a major challenge for the field. In addition to established tumor markers, certain patient genetic factors seem clearly associated with cancer progression. For instance, germline genetic polymorphisms in SRD5A, UGT2B, and HSD17B were shown to be associated with progression in Caucasian and Asian patients with prostate cancer after radical prostatectomy (8–10). In a previous study, 4 SRD5A2 single nucleotide polymorphisms (SNP; rs2208532, rs12470143, rs523349 (V89L), and rs4952197) were associated with biochemical recurrence (BCR) after radical prostatectomy in Caucasians and Asians (9). The strongest effect was conferred by the SRD5A2 V89L nonsynonymous SNP (rs523349C allele) with an HR of 2.87 [95% confidence interval (CI), 2.07–4.00; P = 4 × 10−10; 48% BCR). In addition, 2 SNPs, rs518673T in SRD5A1 and rs12470143A in SRD5A2, were associated with a reduced BCR rate (HR = 0.37; 95% CI, 0.19–0.71; P = 0.003 when combined; 16% BCR) compared with noncarriers (38% BCR). Such results support a significant effect of inherited genetic variations in the androgenic pathways on hormonal homeostasis and prostate cancer recurrence. Despite the identification of such potential biomarkers, however, there is a clear lack of biologic data explaining these findings.
It is hypothesized that polymorphisms in SRD5A genes affect the corresponding exposure to sex steroids of androgen-responsive cells, which may impact cell proliferation and cancer progression. At present, the influence of SRD5A polymorphisms linked to recurrence and progression in patients with prostate cancer on the systemic and prostatic sex-steroid hormonal environment remains undetermined. To gain potential insight into their biologic effects, we sought to evaluate the association of previously reported prognostic markers in SRD5A1 and SRD5A2 with levels of circulating and prostatic sex steroids in the same cohort of patients with prostate cancer.
Patients and Methods
This study was based on a cohort of 526 Caucasians diagnosed with prostate cancer recruited at the CHU de Québec-Hotel-Dieu de Québec Hospital (Québec, Canada) between 1999 and 2002, as described (8, 9). For the specific purpose of this study, available plasma and tissue samples were studied (numbers are indicated in Tables), and we excluded patients who received hormonal treatment. Patients did not receive 5-AR inhibitors (5-ARI) in this study. Two high-volume surgeons performed all surgeries for these patients (Drs. L. Lacombe and Y. Fradet). A fragment of fresh prostatic tissue was selected by the pathologist from the radical prostatectomy specimen in the area containing tumor tissue. Microdissection of tumors was not performed. Each specimen was then immediately snap-frozen and kept at −80°C. The remaining prostatic tissue was fixed and submitted in its entirety for histologic examination. Gleason score and pTNM stage were evaluated with paraffin sections. Detailed clinical information was available from a preoperative evaluation and medical records. All participants provided written consent before surgery for the analysis of their genome and corresponding hormone levels. The local research ethics committee approved the research protocol. Analyses described below were conducted blinded.
Genomic DNA was prepared from peripheral blood mononuclear cells collected from patients on the morning of a preoperative ambulatory clinical visit. All samples were kept frozen at −80°C until the time of study. Genomic DNA was extracted using the QIAamp DNA Blood Mini Kit (QIAGEN Inc.) and stored at −80°C. For genotyping, PCR was performed using Sequenom iPLEX matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry, as described (9).
Analyses of steroid levels in plasma and prostatic tissue samples
Dehydroepiandrosterone (DHEA), 5-androsten-3β, 17β-diol (5-diol), testosterone (testo), DHT, androsterone (ADT), androstane-3β-17β-diol (3β-diol), estrone (E1), estradiol (E2), 4-androstenedione (4-dione), ADT-glucuronide (ADT-G), androstane-3α, 17β-diol 3-glucuronide (3α-diol-3G), androstane-3α, 17β-diol-17 glucuronide (3α-diol-17G), DHEA-sulfate (DHEA-S), and E1-Sulfate (E1-S) were purchased from Steraloids. Deuterated isotopes of hormones, namely DHEA-d3, testo-d3, DHT-d3, E1-d4, E2-d4, ADT-d3, 3β-diol-d3, 4-dione-d7, androstane-3α, 17β-diol 17-glucuronide-d3 (3α-diol-17G-d3), E1-S d4, and ADT-S d2, were purchased from C/D/N Isotopes. Plasma steroid measures were based on a procedure previously described (11, 12). Steroids measured in plasma were DHEA-S, DHEA, 5-diol, testo, DHT, 3β-diol, 4-dione, ADT, E1-S, E1, E2, ADT-G, 3α-DIOL-3G, and 3α-DIOL-17G. For tissue, a 50-mg frozen tissue section of prostate was transferred to a 12 × 75 mm glass tube containing 250 μL of 12.5 mmol/L ammonium bicarbonate and homogenized. To assess total steroids, namely total (unconjugated and conjugated) T, DHEA, 5-diol, DHT, 3β-diol, and ADT, 50 μL of the deuterated internal standards were added to the homogenized samples, following by the addition of 0.5 mL of freshly prepared hydrolysis buffer containing β-glucuronidase/sulfatase enzyme (Helix pomatia, type HP-2, ≥500 U β-glucuronidase, and ≥37.5 U of sulfatase activity) as described (13). Samples were incubated overnight at 37°C for hydrolysis and then extracted with 4 mL of chlorobutane:ethyl acetate (3:1) mixture. The organic layer was transferred to a clean glass tube, evaporated to dryness at 35°C under nitrogen gas, and dissolved with 100 μL of sodium bicarbonate (pH 9.0) and 100 μL of dansyl chloride (1 mg/mL in acetone). Then, 3 mL methanol:water (1:4) mixture was added to the sample, and solid-phase extraction was performed with a Strata-X Reversed SPE Phase Sorbents 60-mg columns (Phenomenex) previously conditioned with 1 mL methanol followed by 2 mL of water. The loaded cartridges were then sequentially washed with 3 mL of water and 3 mL of 55% methanol. The cartridges were dried under full vacuum. The androgenic compounds were eluted with 3 mL of 90% methanol and evaporated to dryness at 45°C under nitrogen gas. Next, androgens were derivatized and analyzed by gas chromatography–mass spectrometry as described (8). The sulfatase and β-glucuronidase mixture from H. pomatia was tested for steroid-converting enzymatic activities, and it was noted that this specific preparation presents some HSD3B activity (<3%, data not shown). Lower limit of quantification for T, DHEA, 5-diol, DHT, 3β-diol, and ADT were 300, 1,000, 500, 50, 100, and 250 pg/g, respectively.
Statistical analyses
To adjust for differences in the absolute levels of sex-steroid hormones, we calculated residuals of the natural logarithm of the hormone level regressed on age at blood donation and smoking status. We assessed the association of SNPs with variation in hormone levels by performing the regression of hormone residuals on each SNP independently for 2 models: recessive and dominant with one degree of freedom. We considered the association of a SNP with variation in hormone levels to be significant if the P value was ≤0.05. To facilitate comparisons between groups, we displayed the hormone level as untransformed data by using the geometric mean and SEM. Statistical analyses were performed using SAS Statistical Software version 9.2 (SAS Institute) and using PASW statistics version 17 (SPSS Inc.). Owing to the exploratory nature of this study on androgen metabolism in patients with prostate cancer, no correction was made for multiple testing.
Characteristics and descriptive statistics of the study cohort are listed in Table 1. The cohort was mostly composed of white men who underwent radical prostatectomy at L'Hôtel-Dieu de Québec Hospital between February 1999 and December 2002 (8). Tables 2 to 4 present data for prostatic and circulating steroid levels in samples from patients heterozygous or homozygous for the minor allele in comparison with levels measured in samples from homozygous carriers of the major allele.
SRD5A1 rs166050, which is associated with higher risk of BCR, was associated with higher levels of numerous prostatic steroids, particularly DHEA (60%, 25.94 ng/g vs. 15.76 ng/g; P = 0.045) and ADT (100%, 13.51 ng/g vs. 6.77 ng/g; P = 0.015), in homozygous carriers for the minor allele rs166050C (Table 2). No significant change in the concentrations of steroid hormones was observed in the circulation in relation to this SNP (Supplementary Table S1), both in circulating blood and prostatic tissues (Tables 2–4).
Five SNPs in SRD5A2 were evaluated, of which 4 (rs2208532, rs4952197, rs523349 (V89L) and rs676033) were significantly associated with a higher risk of BCR, and 1 marker (rs12470143) with lower risk of BCR in Caucasians and Asians (9). Levels of prostate DHT and 3β-diol were particularly affected by one SRD5A2 polymorphism (rs676033). Indeed, patients homozygous for the risk allele rs676033A, in close genetic linkage with rs523349 (V89L), displayed 30% higher prostatic levels of DHT (P = 0.04) and 40% higher 3β-diol (P = 0.03) compared with GG/AG. In addition, plasma ADT levels were also significantly higher (17%; P = 0.04; Supplementary Table 2) in the presence of this polymorphism. Interestingly, tissue levels of 5-diol were higher for most unfavorable SNPs, reaching significance for rs4952197 (37% higher; P = 0.012) and rs523349 (30%; P = 0.030) but not attaining significance for rs2208532 (38%; P = 0.052) and rs676003 (26%; P = 0.058). Remarkably, we found a significant association between the SRD5A rs2208532 SNP and intraprostatic testosterone levels. Indeed, carriers of this high-risk allele had a 32% increase in prostatic testosterone levels (P = 0.038). An apparent lower level (20%) of prostatic testosterone was observed with the protective rs12470143 allele, but this difference was not statistically significant (P = 0.13). Table 3 lists details of the comprehensive effects of SRD5A2 SNPs on prostatic steroid hormone levels.
Of 14 steroids measured in plasma, significant associations were observed for glucuronide (-G) metabolites of DHT in relation to SRD5A2 markers (Fig. 1, Table 4, and Supplementary Table S2). The protective marker rs12470143A was associated with significantly higher 3α-diol-17G levels (15% for homozygotes; P = 0.048), whereas the opposite was observed for carriers of an unfavorable allele of that gene. In particular, rs2208532G was associated with significantly lower concentrations (10–20%) of ADT-G (P = 0.028) and 3α-diol-17G (P < 0.001). Interestingly, the risk alleles rs676033 and rs523349, in strong linkage disequilibrium in Caucasians (r2 = 0.90), were both associated with elevated levels of 3α-diol-3G (24% for rs523349CC, P = 0.036; 20% for rs676033AA, P = 0.039). Two SRD5A2 markers (rs12470143 and rs2208532) were also associated with an increase and decrease, respectively, in prostate volume at time of surgery (not shown).
SRD5A genes encode rate-limiting enzymes involved in DHT formation in the prostate and several other tissues, particularly the liver and skin. Inhibition of these enzymes is the theoretical basis for chemoprevention strategies (5, 6) and was also recently shown to reduce prostate cancer progression in low-risk disease (14). In agreement with these previous findings, inherited germline variations in SRD5A1 and SRD5A2 were positively associated with BCR after radical prostatectomy in localized disease in both Caucasians and Asians (9). These results suggest that SRD5A genes may represent potential biomarkers of disease progression and response to treatment.
Our data suggest that SRD5A polymorphisms affect androgen metabolism in patients with prostate cancer as reflected by significant changes in circulating steroid glucuronide metabolites of the potent hormone DHT. Indeed, 4 of the 5 previously identified SRD5A2 markers (rs12470143, rs2208532, rs523349, rs676033) affect circulating glucuronide levels. The SRD5A2 rs12470143 protective marker is associated with higher levels of 3α-diol-17G in patients with prostate cancer, whereas the SRD5A2 rs2208532 risk allele is associated with lower levels of both 3α-diol-17G and ADT-G. Also, the genetically linked rs676033 and rs523349 risk variants are associated with increased levels of androgen glucuronides, namely 3α-diol-3G. Thus, these SRD5A markers significantly affect sex-steroid profiles of DHT metabolites in circulation of patients with prostate cancer. Indeed, T and DHT are rapidly transformed in the human prostate by several metabolic enzymes (15, 16). Moreover, DHT and its metabolites are further metabolized by UDP-glucuronosyltransferases (UGT), namely UGT2B15, UGT2B17, and UGT2B28, to yield their downstream inactive metabolites such as 3α-diol-3G, 3α-diol-17G, and ADT-G that are subsequently released into the circulation (Fig. 2; refs. 17–19). These major inactive steroids are considered biomarkers for intraprostatic DHT synthesis and exposure (20). Therefore, the presence of SRD5A2 prognostic markers impacts androgen formation in these men, whereas additional steroidogenic enzymes would be involved in DHT biotransformation before their inactivation by UGTs. In support of our findings, results obtained with the SRD5A2 rs12470143 and rs2208532 SNPs are in complete agreement with previous findings indicating an impact of these key genetic variations on circulating androgen metabolites rather than on circulating SRD5A substrates (21, 22).
Moreover, SRD5A variants are associated with sex-steroid exposure in the prostate of patients with cancer. Remarkably, the rs2208532 SNP was linked with a 32% increase of intraprostatic testosterone levels, combined with reduced circulating glucuronide levels, suggesting that this high-risk allele is associated with reduced 5α-reductase enzyme efficiency. In the same line of thought, in the presence of the low-risk allele rs12470143, a non-significant reduction (16%) in prostatic testosterone levels combined with higher glucuronide levels suggest that this SNP is associated with high enzyme activity. Interestingly, the nonsynonymous V89L variant of SRD5A2 (rs523349), previously associated with aggressive forms of the disease (23), has been described as a low-activity allele in vitro (24). This coding SRD5A2 variant has been reported to impact sex-steroid concentrations in different ethnic groups, whereas an ethnic-specific distribution and linkage with other SRD5A2 alleles also has been observed (21, 24–27). Measurement of steroid levels in the prostate revealed that individuals carrying a tightly linked variation to rs523349 (e.g., rs676033) display significantly higher intraprostatic DHT and 3β-diol levels, higher circulating levels of ADT (a 5α-reduced metabolite of DHT; Fig. 2), and no significant alteration in circulating T or DHT levels. According to these observations, we hypothesize that the V89L rs523349 SNP or another variation in linkage disequilibrium such as rs676033 located in the promoter region of the gene would modulate 5α-reductase activity/expression within prostate cells. Further studies are definitely required to evaluate the molecular impact of the rs523349/rs676033 in target cells of patients with cancer.
Regarding SRD5A1 markers, no significant changes were observed in circulating sex-steroid levels. Among the statistically significant results, our data reveal an accumulation of ADT without changes in steroid glucuronide levels, as observed for SRD5A2 markers. These higher levels of ADT indicate that this variation might enhance enzyme activity, also hypothetically favoring BCR in these patients. As previously suggested (28), this accumulation of ADT combined with the absence of significant changes in T levels in SRD5A carriers may also indicate that the alternate route of androgen biosynthesis not involving T may perhaps predominate in these individuals. In addition, high levels of ADT in these patients could theoretically fuel DHT synthesis by the concerted action of other pathways such as the HSD17B3 and HSD17B6 enzymes, supporting androgen formation and conceivably recurrence of elevated prostate-specific antigen.
Unfavorable SNPs in SRD5A2 are also linked to an elevation at the target cell level of other potent steroid hormones such as 5-diol secreted by the adrenals. The mechanism leading to enhanced exposure of 5-diol in these individuals may be a result of additional and complex interplay between 5α-reductases and other key steroidogenic enzymes expressed in the prostate, for example, CYP17A, HSD3B, and HSD17B. If further confirmed in additional independent studies, this enhanced exposure to 5-diol may be of biologic significance in the context of prostate cancer progression because this adrenal precursor was elegantly shown to be a natural hormone with androgenic properties in human prostate cancer cells (29, 30). Indeed, 5-diol can activate the androgen receptor without being metabolized to T or DHT, especially in the presence of the coactivator ARA70 that notably enhances its androgenic properties (29). Moreover, 5-diol also has estrogenic activity at physiologic concentrations and can bind the estrogen receptor α (ERα), although at low levels in the normal prostate, and trigger an estrogenic response (31). Thus, additional studies of this sex-steroid hormone are warranted in the context of cancer progression at different stages of the disease. Moreover, the level of 3β-diol, an important metabolite of DHT, is also altered in the presence of SRD5A prognostic marker (rs676033) and may potentially impact cancer progression as well because it is the endogenous ligand of ERβ in human prostate (32). ERβ is the most abundant estrogenic receptor in prostatic basal cells and is involved in major cellular pathways, including inflammation processes, differentiation, and apoptosis, thus supporting a role for this nonaromatized estrogenic steroid in the prostate (32, 33).
Overall, inherited SRD5A variations seem to have noteworthy physiopathologic consequences. Indeed, any subtle and persistent variation in sex-steroid hormone levels and/or their relative ratios may modify the course of a slow-progressing disease such as prostate cancer over several years. Data further reinforce the significance of SRD5A genes in hormone metabolism and the biologic relevance of previous associations observed between this pathway and clinical outcomes. The assessment of SRD5A markers based on individual patients' germline genetic variations may also lead to a better patient stratification in future 5-ARI clinical trials, targeting therapeutic interventions to optimize hormonal manipulation in patients with a high risk of recurrence and helping to identify patients who would more likely benefit from treatment. However, it is currently unknown if any SRD5A genotypes, such as the low-risk SRD5A2 allele rs12470143 or any of the high-risk variants (rs2208532, rs676033, rs523349), may modify 5-ARI response. The impact of these common germline polymorphisms should certainly be addressed in future studies.
To our knowledge, this is the first report of sex-steroid measurements in both the circulation and prostatic tissues of patients with prostate cancer in relation to inherited genetic markers associated with recurrence. The strengths of the study include the use of gold standard mass spectrometry–based sex-steroid assays, fasting blood sampling on the morning of the surgery for all patients with paired prostatic tissues collected at prostatectomy, the selection of SRD5A markers (n = 7) associated with biochemical recurrence (9) and the biologic plausibility of the association. Limitations are related to (i) the availability of only single blood and tissue samples for measurement of steroids and (ii) quantification of steroids in available prostate cancer samples containing surrounding peritumoral tissues, because no tumor microdissection was performed. The latter may have resulted in potential underestimation of the impact of these germline variants on overall androgen metabolism in cancer samples. Hence, although this is the first report of sex steroids measured in human prostatic tissues in relation to germline SNPs in key androgenic genes, one must bear in mind that the number of cases assessed was limited owing to the infrequency of acquiring samples from which a relatively large quantity of fresh-frozen prostate cancer tissue could be obtained for steroid measurements. Therefore, these analyses are exploratory, with no attempt to correct for multiplicity. Additional studies analyzing both circulating and prostatic tissue levels of a wide range of sex-steroid hormones in patients with prostate cancer are clearly necessary to gain important information on steroid biotransformation and prostate cancer progression.
We conclude that the assessment of host genetic variants in key steroidogenic pathways, such as those governed by SRD5A genes, represents additional indications that the inherited genetic background influences the hormonal microenvironment to which cancer cells are exposed. Our results support that SRD5A genetic variations modify sex-steroid exposure to potentially promote cancer growth and proliferation. Further studies are required to fully characterize at the molecular level the impact of functional variations in SRD5A genes in both normal and prostate cancer cells. Moreover, markers in SRD5A genes, especially the SRD5A1 rs166050, SRD5A2 rs12470143, rs2208532, and rs676033/rs523349 SNPs, may ultimately represent clinically relevant prostate cancer indicators and lead to more personalized management of the most prevalent cancer in men, especially early in the course of the disease.
Disclosure of Potential Conflicts of Interest
E. Lévesque, Y. Fradet, L. Lacombe, C. Guillemette, have ownership interest (including patents). No potential conflicts of interest were disclosed by the other authors.
Authors' Contributions
Conception and design: E. Lévesque, C. Guillemette
Development of methodology: E. Lévesque, C. Guillemette
Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): E. Lévesque, I. Laverdière, L. Lacombe, P. Caron, V. Turcotte, B. Têtu, C. Guillemette
Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): E. Lévesque, I. Laverdière, M. Rouleau, V. Turcotte, C. Guillemette
Writing, review, and/or revision of the manuscript: E. Lévesque, I. Laverdière, L. Lacombe, M. Rouleau, B. Têtu, Y. Fradet, C. Guillemette
Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): E. Lévesque, L. Lacombe, C. Guillemette
Study supervision: E. Lévesque, C. Guillemette
Grant Support
This work was supported by Canadian research grants from the Cancer Research Society (C. Guillemette), Fonds de recherche du Québec–Santé (FRQS), and the Canada Research Chair Program (C. Guillemette). E. Lévesque is the recipient of a Prostate Cancer Canada rising star award (RS2013-55). C. Guillemette holds the Canada Research Chair in Pharmacogenomics (Tier II). I. Laverdière and M. Rouleau are both recipients of a Frederick Banting and Charles Best Canada Graduate Scholarship award from the CIHR. I. Laverdière is a recipient of a clinician-scientist graduate scholarship from FRQS.
The authors thank Dr. A. Bélanger for helpful discussion, the biostatistics services of the clinical research platform (CHUQ Research Center) for their support, as well as M. Orain, J. Ouellette, É. Audet-Walsh, and C. Flageole for their technical support in the preparation of tissue samples before extraction and measurement of hormones by mass spectrometry.
Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).
- Received April 22, 2013.
- Revision received October 8, 2013.
- Accepted November 6, 2013.
- ©2013 American Association for Cancer Research.


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Assignments Practical Chinese Reader - 實用漢語
PCR Lesson 8 Assignments
1. Vocabulary & Grammar Survey:
After reading and reflecting on the information introduced in your textbook and in the Study Guide section for this lesson, answer the following questions:
( Answers in this section will only be recorded for registered users. Login to get credit for this section. )
I have reviewed the new vocabulary introduced in lesson 8 using one or more of the following strategies:
- (please list)
- (please list)
Answer the following questions based on your reading and review of your textbook and the Study Guide section for lesson 8.
1. In Chinese, personal titles are placed after the surname, so instead of saying Dr. Xie we say 謝大夫.
2. What is an appropriate response after someone thanks you, or offers you a compliment.
3. 她爸爸,媽媽都茶。
4. 我的中國朋友煙。
5. 你們都漢語書嗎?
(5 pts) due: Monday, Sep 29th
2. Writing:
Use the calligraphy practice sheet to practice writing the characters introduced in this lesson. Fill-in the empty columns with characters of your choosing.
As an alternative you may write one complete Chinese sentence in pinyin or characters for each character introduced in lesson 8.
As an alternative you may write one complete Chinese sentence in pinyin or characters for each character introduced in lesson 8.
(10 pts) due: Wednesday, Oct 1st
3. Exercises:
- Work with a classmate to unscramble the sentences on the L7-9 Dialogue Practice worksheet and arrange them into a coherent dialog. Get an extra point for presenting your dialog to the class. (answers)(0 pts) due: Wednesday, Oct 1st
- Complete the homework practice sheet (plain text).
(answers)(10 pts) due: Monday, Oct 6th
4. Cultural Questions:
The following questions relate to the cultural section of this lesson. Generally you will be able to find the answers by reading your textbook.
( Answers in this section will only be recorded for registered users. Login to get credit for this section. )
1. What was the ultimate aim of the reform of Chinese writing system?
2. The two basic strategies used to accomplish the simplification of Chinese characters was to reduce the number of characters and number of strokes.
(2 pts) due: Monday, Oct 6th
5. Classroom Activities:
- Chinese Tea Culture - date: Monday, Oct 6th
- Asking 哪, 什麼 and 誰 Questions - Ask three people three questions. One question each using 哪, 什麼 and 誰date: Monday, Oct 6th
- Asking 那是什麼?是誰的? - Ask a classmate 什麼 and 誰的 questions following the sample:
A: 這是我的漢語書。date: Monday, Oct 13th


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7 Things Your OB/GYN Wants You To Know About Your Vulva
What do you know about vulvas? The vulva may be one of the most misunderstood body parts on the human body. It's definitely the most often misnamed. Usually when people talk about that part of the body, they say "vagina." But it turns out that we've all been saying it wrong. The vagina is the canal inside the body, where tampons go. And everything else? All the outside stuff — including the labia minora, labia majora, clitoris, the vaginal opening, and the urethra — is the vulva.
So unless you're talking about tampons or sexual penetration or having a baby, chances are most of the time when you're referring to your "vagina," you really mean to say your "vulva." And that's just one of the many things about your vulva that Dr. Sherry Ross, women's health expert and author of She-ology: The Definitive Guide to Women's Intimate Health. Period., wants everyone to know about vulvas. Dr. Ross is an OB/GYN who has dedicated her practice to helping women and other people with vulvas understand their body parts, in order to live a healthier and fuller life.
Here are the top things Dr. Ross wishes everyone knew about their vulva. (And just to be clear, while "woman" is used throughout below, it's important to acknowledge that not all women have vulvas and not all people with vulvas are women. All of the advice applies to all people with vulvas, regardless of their gender.)
1. Take A Selfie
So many women wonder if their body is normal looking. "You must get to know your vulva and vagina, up close and personal," Dr. Ross says. "My first and foremost advice to women is to get to know your parts, know what your 'normal' is so you will know when a potential problem arises.
Dr. Ross suggests puling out a mirror and getting to know your vulva. "Your vaginal health depends on it," she says.
2. Not Everything Is A Yeast Infection
"Of all the infections that can affect the vulva, a yeast infection is the most common," Dr. Ross says. "It's estimated that 75 percent of women will experience a yeast infection in their lifetime. But just because you have itching of the vulva doesn't necessarily mean you have a yeast infection. The vulva can be delicate and temperamental, often affected by everyday routines including diet, medications, stress, fragranced body and laundry soaps, douching and sex, especially if you haven't had adequate foreplay. Anything that disrupts the pH balance makes the vulva and vagina a not so happy place."
3. Ditch The Panty Liners
"The worst thing a woman can do for the skin of the vulva is wearing a sanitary napkin or panty liner every day to collect accidental loss of urine or normal vaginal discharge that can get on your underwear," Dr. Ross says. "Sanitary pads and panty liners can disrupt and irritate the skin of the vulva when worn daily. Many are scented with fragrances or contain synthetic materials with chemicals that cause skin dryness and irritation. Vulvar skin dryness and irritation can cause chronic itching of this delicate area of the vagina. A condition called the 'scratch-itch' cycle can occur as a result of wearing sanitary napkins and panty liners every day. Even the most organic and natural panty liners can disrupt the delicate skin of the vulva."
4. You Can Be Allergic To Your Partner's Sperm
"Being allergic to your partner's sperm is a rare condition, but it can happen. It tends to be under-diagnosed," Dr Ross says. "It happens when a woman produces antibodies against certain proteins found in seminal fluid. Symptoms appear 10 to 30 minutes after contact with semen. Depending on where the semen was will determine the symptoms. Symptoms include redness, swelling, pain, itching, blisters and a burning sensation in the vulva."
5. It's OK To Use Soap On Your Vulva
"The most common misconception of the vulva is that you cannot use soap on the vulva since it may disrupt the vagina's sensitive pH balance," Dr. Ross says. "Using the wrong types of soap can cause irritation and bad odor. Avoid soaps which are heavily perfumed, contain too many unnatural ingredients, or have antibacterial properties which upset the natural balance of your body. Using a gentle, non-fragranced soap and natural skin moisturizer daily is ideal, especially ones made specifically for the vulva. Your vulva does need a special cleaning routine and it usually begins with using a non-fragranced soap and warm water."
6. You Can Get Acne On Your Vulva
"A healthy vagina needs hygienic attention similar to the way we care for our face," Dr. Ross says. "The vulva has sweat glands and hair follicles that are prone to dirt buildup, just like any other of the body with hair and sweat. Between urine, sweat, and being so close to the anus, cleaning the vulva regularly is critical to prevent dirty bacterial buildup which could lead to acne, pimples, rashes, and sores. Keeping the vulva clean with an intimate vaginal wash and preventing dryness of the skin will help avoid unwanted hygiene obstacles."
"The skin of the vulva is prone to dryness if not taken care of properly," Dr. Ross says. "If you don't moisturize your vulva, the skin will become dry, which can cause irritation, itching, burning and pain. Feminine hygiene products including fragrant soaps, bubble bath liquids, sanitary wipes, laundry detergent, and sexual lubricants are some of the products that lead to vaginal dryness. Extra virgin coconut oil (EVCO) in a warm bath helps naturally moisturizes the vulva helps prevent the disruptive symptoms caused by vaginal dryness. I recommended taking baths with EVCO nightly to prevent dryness."
So there you go: seven things your OB/GYN wishes you knew about your vulva.


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Pick your suite today!
Call today to book your appointment to find out about The Rennie Seniors Apartments.
Come in and discover our upcoming, new boutique-style rental building offering only 48 independent living suites.
Visit The Rennie Presentation Center here inside The Royal Henley.
To book your appointment, Call Jessica or Krista Today at (289) 241-7400 .


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This aromachologie repairing oil has been formulated to strengthen dry and damaged hair. It is enriched with almond oil, vitamins and omega nine as well as exotic essential oils that will nourish the hair from within, making it shiny and healthy.
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Protect your hair from the effect of heat and damage with this aromachologie repairing oil from the house of L'Occitane.
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Most California road laws apply for both vehicles and motorcycles, but there are a few motorcycle-specific laws that could easily get you in trouble.
Since most of these laws can be complex, it is advisable to contact an LA Motorcycle Accident Lawyer for counsel if you or your loved one has been injured in an accident. Read on for the most important California motorcycle laws to be aware of.
Right of way
The Department of Motor Vehicles (DMV) insists that the right-of-way rules in California promote traffic safety for drivers and motorcyclists. Statistics seem to jibe with this statement as nearly half of all motorcycle accidents in California are a result of right-of-way violations. Your lawyer can help you get a better grasp of the right of way while riding a motorcycle in California.
Speed limits
As regards speed, California's limit is 65mph, albeit you can go at 70mph in posted areas. Posted limits vary based on location and road type.
Keep in mind that California has a basic speed law which prohibits motorists from driving beyond certain speed limits in certain weather and road conditions, notwithstanding the posted limit. If the road you are riding on is rough, it is raining, or there is a traffic jam, you could be arrested for speeding even if you are within the posted speed limit. Motorcyclists are particularly urged to adhere to this law as motorcycles cannot handle bad road and weather conditions as well as automobiles.
Lane splitting
Just recently, California lawmakers passed a bill that allows motorcyclists to lane-split as long as they do it in a safe and prudent manner. Lane-splitting is the practice of driving a motorcycle between two rows of moving or stopped traffic.
Limitations on the practice include not driving beyond certain speed limits and completely not doing it in certain situations.
Being a new law, however, the guidelines for this practice aren't complete, and the safety standard remains "safe and prudent" driving.
Rider safety equipment
For your safety and that of your passengers, California law requires you to adhere to the following rules:
- Both you and your passenger should wear helmets
- You should have a motorcycle license with you while on the road
- Any motorcycle manufactured after 1978 should have daytime headlights
Turn signals
Just like automobiles, motorcycles on California roads are required to have working front and rear turn signals. Exempt are motorcycles manufactured and first registered before 1973.
Handle-bar height
In California, you are not allowed to drive a motorcycle whose handlebars are more than six inches above your shoulders when you're seated.
Motorcycle exhaust systems
An anti-tampering act enacted by Governor Arnold Schwarzenegger back in 2010 gives police officers the authority to give tickets to motorcyclists who have tampered with their exhaust systems. The law took effect in 2013 and only applies to motorcycles and exhaust systems built starting 2013.
These are some of the laws that you need to keep in mind if you are planning to ride a motorcycle in California. Consult your lawyer for more details to avoid getting in trouble with the police for laws you didn't know existed in the first place.


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We came across this quote by Albert Einstein in which he beautifully articulates what he felt is the role of education. It reveals an ambitious and holistic view that you'd expect from such a man, yet what he describes simply makes perfect sense. In essence it describes Montessori philosophy. It describes what we aim to achieve through the Montessori methods and that is to consider the whole child, giving equal weight to their emotional/social development as the academics.
"It is not enough to teach a man a specialty. Through it he may become a kind of useful machine but not a harmoniously developed personality. It is essential that the student acquire an understanding of and a lively feeling for values. He must acquire a vivid sense of the beautiful and of the morally good. Otherwise he - with his specialized knowledge - more closely resembles a well-trained dog than a harmoniously developed person. He must learn to understand the motives of human beings, their illusions and their sufferings, in order to acquire a proper relationship to individual fellow men and to the community.
These precious things are conveyed to the younger generation through personal contact with those who teach, not - or at least not in the main - through textbooks. It is this that primarily constitutes and preserves culture. This is what I have in mind when I recommend the 'humanities' as important, not just dry specialized knowledge in the fields of history and philosophy.
Overemphasis on the competitive system and premature specialization on the ground of immediate usefulness kill the spirit on which all cultural life depends, specialized knowledge included.
It is also vital to a valuable education that independent critical thinking be developed in the young human being, a development that is greatly jeopardized by overburdening him with too much and with too varied subjects (point system). Overburdening necessarily leads to superficiality. Teaching should be such that what is offered is perceived as a valuable gift and not as a hard duty."
—Albert Einstein, "Education for Independent Thought" New York Times, 5/10/1952
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Chicago, Ill., April 8, 2017 – Junior Anna McKee tossed a four-hit complete game shutout to lead the Washington University in St. Louis softball team to a 3-0 win in game one of a doubleheader Saturday at the University of Chicago. The Maroons posted a 3-1 victory in game two.
WashU 3, Chicago 0 – Game One
Sophomore Taylor Arends gave WashU the 3-0 lead in the Bears' first at-bat with a three-run homerun to left center. The homerun for Arends was her first of the year and third of career.
McKee (8-2) tossed her seventh complete game of the year and struck out 10. She got out of a jam in the second after senior Kenzie James threw a runner out at the plate, and then escaped bases loaded in the sixth with a fly out to left.
James went 3-for-4 with a run scored, while Arends was 2-for-3 with a homerun, a run scored and three RBIs. Sophomore Josi Elder did not have an official at-bat after recording three walks. The Bears had six hits in the win.
Chicago 3, WashU 1 – Game Two
Chicago (11-8) jumped on junior starter Maggie Clapp for two runs on two hits in the second inning. Clapp got out of the inning with her fourth strikeout of the game. The Maroons added a run in the third to push the lead to 3-0.
The Bears ended a nine-inning scoreless drought in the fourth scoring one run on two hits. Junior Ashley Madsen singled to lead off the inning and then stole second. She came around to score on an RBI single by senior Hannah Mehrle.
WashU put together a rally in the fifth after junior Mackenzie Gauden and senior Halle Steinberg singled with two outs, but Madsen struck out to end the threat.
Clapp (5-5) took the loss in game two allowing six hits and three earned runs in five innings pitched. She struck out six and walked one. Gauden came in relief and pitched a perfect sixth inning. The Bears were limited to four hits in game two and committed two errors.
WashU (14-7) closes out the four-game series with two games Sunday at Chicago. First pitch in game one is at 11 a.m.
BEAR NOTEBOOK: WashU leads the all-time series with Chicago, 9-3, and the teams met for the first time since 2007 … Taylor had her 15-game reached base streak come to an end in game two … WashU is 13-2 when scoring first, and 1-5 when the opponent scores first … Senior Janet Taylor tied the WashU all-time walk record (64) in game one.


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Hats for fishing the Florida waters. Assorted colors with Fish or our favorite sayings: "Shut Up & Fish" [SOLD OUT] or "Filet & Release". Only a few of these left so grab them while you can! Use Drop Down menu to select options. We send color of our choice. If you want a certain color, please note this in the "comments" field at checkout. See actual quantities/choices below.
What's left?Filet & Release = 7 Green Bill, 3 Charcoal Bill, 4 Blue BillGrouper = 1 Charcoal Bill, 1 Blue BillPriced for Clearance!


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This type of coral is colourful and as the name suggests a soft type of coral. It makes for a beautiful dive and if you are a photographer, some amazing shots. Some are white, red, and colours in between. Normally in these areas fish life is abundant, as are little critters due to the nutrients flowing through the water.
Spend time looking for the small critters and wondering at all the colours!


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One of the wasteland worse nightmare… This huge, bone-plated mutant roams the world of Eden killing any creature passing by. The Bamakas call him "The Bayakoyé", which means the Demon of Destruction.
Horde profile created by Olivier "Vigoli" Vigouroux, winner of the Summer 2016 profile creation contest!
This is what he tells about this profile:
"For me the Bayakoyé is a dreadful beast. Everybody fears it and neither the allied nor the enemies want to get too close from it. So on its way, it kills everything, and some kind of scavenger pack follows it to eat what remains… So it is, without really willing it, the Bayakoyé is the origin of small pack of fierce beasts.
Metal miniature supplied unassembled and unpainted.


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Maybe it comes from all those beautiful summers as a child where both days and nights seemed endless,
but every summer since my first was born, I seem to be under some unbroken illusion that I will finally have the time to complete those projects I've been meaning to get to all year long…
You'd think I'd learn after nearly a decade, but ever the optimist, I've held onto the hope that big things will happen each summer!!
What I'm really starting to realize now is that they are happening…
just not in the way I'd expected.
Instead of a finally neat home,
I find it's way messier..
Instead of cleaner kids,
they are definitely dirtier…
Dinner before 6:30?
Try 7:30…and even 8:30 sometimes!
See, the house is messier,
the kids stinkier,
the dinners later,
Yeah, we might still be trying to get to that bucket list I wrote about at the start of summer, but we've been places, and we've done things, and we've just enjoyed being together.
I've got a neighbor that is in his 80's. His wife passed on, and his children live elsewhere, so he lives alone.
Sometimes when life has been especially busy, I'll look out the window at his house where he is often lounging on his front porch,
but I can't help but think how he must long for what I have:
but more than anything,
…that I've learned to let the plans go and just delight in where the Lord leads, messy house, dirty unfed kids and all…