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Authors: CHIN-CHIH CHANG; TING-CHIN CHOU; HAO-YUN CHUANG
Company/Faculty/School: JEN-TEH JUNIOR COLLEGE OF MEDICINE, NURSING AND MANAGEMENT
Country: Taiwan
e-mail: email@example.com
web page: www.wiipa.org.tw
Is it happening that the kitchen knife is not sharp enough when you are cooking? And the whetstone couldn't be found at once, or when we wanted to grind ginger mud, but the grinder is hard to find out. So, we invent a new style cutting board with functions of sharpening, grinding and kitchen knife storage. We hope that the new style of multifunctional cutting board will make cooking preparation more convenient.
AFIOT collaborated with USDC ( Capital 4,000,000USD) firm to develop the product.


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Tell a woman that menopause "only lasts one day," and you may have to duck.
It's true, though: technically, "menopause" is the one-year anniversary of a person's last period, and it only lasts one day.
Perimenopause (the time of hormone fluctuation leading up to menopause) and post-menopause last a whole lot longer, and the entire transition can take up to 20 years in some cases.
In common discourse, the term "menopause" has really come to mean the length of the transition, but there's a danger is using the terms too loosely.
Do any research at all into menopause, and you'll find all over the Internet that "the average age of menopause in the United States is 51." So what happens to a 45-year-old woman who starts experiencing heart palpitations, interrupted sleep, or increased anxiety and depression that can come with hormonal fluctuations?
Believing herself too young for anything menopause-related, she thinks, "Something is wrong with me!" At Gennev, we're heard story after story of women, terrified, going to the ER thinking they're having a heart attack, only to be sent home confused, embarrassed, and frequently with a prescription for antidepressants.
While we would always advise women who are experiencing frightening changes in their bodies to seek medical attention, we think many women would find the transition a whole lot easier if they had more information heading in to it.
So let's talk about the stages and what women may experience. However, it's important to note from the outset that every woman's experience of peri/menopause is as unique as she is, so your journey may follow a different map from your best friend's or even your sister's.
Perimenopause defines the stage of life where a woman's hormones begin to fluctuate differently than the more predictable rises and falls of her normal cycle. Estrogen levels rise and fall unevenly, and the changes begin.
Despite all sorts of sources across the Internet claiming perimenopause typically lasts "about 4 years," anything up to 10 years is closer to the truth. Many women enter perimenopause in their early to mid-40s, but the changes can start in a woman's mid-30s.
In perimenopause, you may notice:
Many women find low-dose birth control pills or a hormonal IUD like the Mirena can help control many of the symptoms of perimenopause.
Congratulations! You've gone a full 12 months without a period.
While some women may see menopause as an ending – to reproduction, to youth, to sexuality – at Gennev, we see menopause as a beginning to the second chapter of life.
Menopause, in our definition, is an invitation: to take extremely good care of yourself, to try out new things, to indulge your wants and desires, to embrace your sexuality and beauty, and to give a whole lot less importance to others' opinions of you.
Yes, the symptoms of menopause can be troubling, but there's no need to let them diminish your quality of life as you step into…
Thanks to longer life expectancies, many women nowadays can expect to live a third (even up to a half!) of their life in menopause.
And this second chapter of life can be rich, fulfilling, active, and vibrant. You just may have to work a little harder to protect your health and quality of life.
In post-menopause, things to be thinking about (and actually, if you're not there yet, start thinking about them now!):
Twenty years may seem like a prison sentence, but it doesn't have to be. There's help for symptoms at every stage, and you'd be surprised at how much better common-sense healthy behaviors can make you feel (eating well, prioritizing sleep, minimizing stress, exercising, hydrating, NOT SMOKING).
At Gennev, we're committed to helping every woman understand her body better, and you can help us do that. We'd like to invite you to share Gennev with the women you care about, especially younger women. Think about it: how prepared were you? Would it have helped if someone had told 40-year-old you about what was happening or coming soon? If you have shared your knowledge, how did you do it? We'd love to know. Hit us up in our community forums, on our Facebook page, or in Midlife & Menopause Solutions, our closed Facebook group.

subset: commoncrawl


text: Costumes By Jeanne I wonder how many of you knew that my wife designs and manufactures her own costumes. I would say not to many of you! Jeanne is an amazing costume designer. She has designed everything from costumes based on characters form Sleeping Beauty to Civil War to Renaissance. Below are just a few pictures of some of the costumes she has designed and made. If you are interested in having a costume designed please use the feedback form to submit any questions. Jeanne and I played Santa and Mrs. Claus for years at a place called High Hill Ranch in an area north of Placerville Ca. known as Apple Hill. Jeanne designed my costume based on an 1800's version of Father Christmas. The coat I am wearing was made from a tapestry showing faces of children from around the world. The vest and pants are red wool with gold buttons. Jeanne's cloak design is what's called a Kinsale cloak. The cloak is made from dark blue wool with a light blue lining and closed at the neck with an antique clasp. The green wool vest and puffed sleeve blouse she is wearing are also dated from the mid 1800's.


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Paperback / softback
Pages: 128
Pub. Date:
November 15 2013
Dimensions: 8.5" x 5.5" x 0.4375"
Rights: Available: WORLD
Drama / DRA013000
Rod Langley's Bethune chronicles the medical and political career of Norman Bethune, a Canadian-born doctor who died a national hero in the Republic of China in 1939. He remains an esteemed figure in China today, for his selfless contributions to the Communist Party of China during the Second Sino-Japanese War (1937–1945), when he trained rural peasants to serve as army medics and set up much-needed base hospitals that ultimately saved thousands of lives.
In the 1920s, Bethune had contracted tuberculosis while in private practice in Detroit and experienced first-hand the limitations of treatment options at the time – as well as the politics within the medical profession that prevented advances in combatting the disease. By demanding that he receive an unproven new treatment, Bethune overcame the illness, and thereafter dedicated himself to revolutionizing respiratory medicine.
A social visionary as well, upon relocating from Detroit to Montreal, Bethune became an outspoken proponent for a national medical plan, despite the prevailing anti-Communist sentiment in Canada. He remained steadfastly committed to the common good, and joined the Communist Party of Canada in 1935. His political convictions took him to Spain, where he supported anti-fascist resistance during the civil war, and ultimately to China, where he came to embody the "barefoot doctor" movement later upheld by Mao Zedong.
Bethune is a study of how one man's vision may shape the world.
Cast of 3 women and 6 men.
"Demystifies the man at the same time as it recreates his boundless energy and chaotic lifestyle."
– Canadian Theatre Review


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Privacy Policy
The Help Hub understands that your privacy is important to you and that you care about how your personal data is used and shared online. We respect and value the privacy of everyone who visits this website, www.thehelphub.co.uk ("Our Site") and will only collect and use personal data in ways that are described here, in a manner that is consistent with Our obligations and your rights under the law.
1. Definitions and Interpretation
In this Policy the following terms shall have the following meanings:
"personal data" means any and all data that relates to an identifiable person who can be directly or indirectly identified from that data. In this case, it means personal data that you give to Us via Our Site. This definition shall, where applicable, incorporate the definitions provided in the Data Protection Act 1998 and EU Regulation 2016/679 – the General Data Protection Regulation ("GDPR"); and
"We/Us/Our" means The Emotional Help Hub UK Ltd, a not-for-profit partnership operating in England and Wales.
2. Information About Us
2.1 We are a group of people who operate as a not-for-profit group to support people with their mental wellnees during isolation caused by Covid-19
2.2 Primary contact for The Help Hub is Ruth Chaloner and can be reached at email@example.com
3. Data We Collect
Depending upon your use of Our Site, We may collect some or all of the following personal and non-personal data:
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4. How We Use Your Data
4.1 All personal data is processed and stored securely, for no longer than is necessary in light of the reason(s) for which it was first collected. We will comply with Our obligations and safeguard your rights under the Data Protection Act 1998 or GDPR at all times.
4.2 Our use of your personal data will always have a lawful basis, either because it is necessary for Our performance of a contract with you, because you have consented to Our use of your personal data (e.g. by subscribing to emails), because it is in Our legitimate interests, or because a vital interest exists. As typical examples, We may use your data for the following purposes:
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4.3 We do not keep your personal data for any longer than is necessary in light of the reason(s) for which it was first collected.
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5.1.8 Rights with respect to automated decision making and profiling.
5.2 If you have any cause for complaint about Our use of your personal data, please contact Us using the details provided in section 2 and We will do Our best to solve the problem for you. If We are unable to help, you also have the right to lodge a complaint with the UK's supervisory authority, the Information Commissioner's Office.
5.3 For further information about your rights, please contact the Information Commissioner's Office or your local Citizens Advice Bureau.
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Your personal data is stored securely within our CRM system. Your personal data may be transferred to, and stored at, a destination outside the European Economic Area ("EEA") by us or by our sub-contractors. We will take all steps reasonably necessary to ensure that your data is treated securely and in accordance with this privacy policy. The Help Hub also seeks to ensure appropriate safeguards in relation to transfer of personal data. Where we transfer your personal data outside of the EEA we utilise standard contractual clauses in supplier contracts or where we store your personal data on Marketing systems provided by US suppliers who have servers located in the US ensuring that these US suppliers are registered under the EU-US Privacy Shield. Further details in this regard is available on request by emailing email@example.com
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You have the right to ask for a copy of any of your personal data held by Us (where such data is held). Under the GDPR, no fee is payable and We will provide any and all information in response to your request free of charge. Please contact Us for more details at firstname.lastname@example.com
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9.1 This website 'thehelphub.co.uk' uses cookies to distinguish you from other users of the site. This helps us to provide you with a good experience when you browse our website and also allows us to improve our site. By continuing to browse the site, you are agreeing to our use of cookies.
A cookie is a small file of letters and numbers that we store on your browser or the hard drive of your computer if you agree. Cookies contain information that is transferred to your computer's hard drive.
We use the following cookies:
9.1.1 Strictly necessary cookies. These are cookies that are required for the operation of our website. They include, for example, cookies that enable you to log into secure areas of our website.
9.1.2 Analytical/performance cookies. They allow us to recognise and count the number of visitors and to see how visitors move around our website when they are using it. This helps us to improve the way our website works, for example, by ensuring that users are finding what they are looking for easily.
9.1.3 Functionality cookies. These are used to recognise you when you return to our website. This enables us to personalise our content for you, greet you by name and remember your preferences (for example, your choice of language or region).
9.2 Our website also uses Google Analytics, a web analytics service provided by Google, Inc.
("Google"). Google Analytics uses "Cookies", as described above. The information generated
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Google will use this information for the purpose of evaluating your use of the website,
compiling reports on website activity for website operators and providing other services
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third parties where required to do so by law, or where such third parties process the information on Google's behalf. Google will not associate your IP address with any other data held by Google.
9.3 In addition to any controls that We provide, you can choose to enable or disable Cookies in your internet browser. Most internet browsers also enable you to choose whether you wish to disable all Cookies or only third party Cookies. By default, most internet browsers accept Cookies but this can be changed. For further details, please consult the help menu in your internet browser or the documentation that came with your device.
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We may change this Policy from time to time (for example, if the law changes). Any changes will be immediately posted on Our Site and you will be deemed to have accepted the terms of the Privacy Policy on your first use of Our Site following the alterations. We recommend that you check this page regularly to keep up to date.
Last updated: 18/03/2020


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Once your order will be ready to leave our warehouse, you will receive a message including the tracking no. assigned to your parcel.
Please consider updated status on your parcel will be available after few hours from the reception of this email.
In case you may need assistance about your delivery, you can contact anytime our Support Team.


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Historical Society guest speaker to inform members on pecan oil and pecan truffles
Pecans – Georgia grown and local. This is the subject of the Grady County Historical Society's monthly meeting next Tuesday night.
Mrs. Mollie Cohen, of Pecan Ridge Plantation, will be the guest speaker at the Feb. 9 meeting. Cohen will tell how her husband, Eric, and brother-in-law, Rob, were raised working in the pecan orchards and how they have expanded their offerings from international markets to producing pecan oil, a light and healthy buttery, nutty flavored oil.
Dr. Tim Brenneman, Professor of Pathology with the University of Georgia, discovered pecan truffles in Georgia. With their large orchards this interested Eric and Rob. Come and learn about their dog, Tate, who is trained to hunt truffles.
Mrs. Cohen is a graduate of UGA with a bachelor's degree in education. She taught for 11 years before joining the family business as Director of Marketing and Sales. She also serves on the Board of Commission for Georgia's Nonpublic Post-Secondary Education Commission.
The Historical Society will meet Tuesday, Feb. 9 at 7 p.m. in the Cairo City Council Chambers inside the Roddenbery Building on North Broad Street.


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Casey Casey is designed by Gareth Casey, and manufactured by hand in Paris, France. They strive to revive the idea of ateliers and reignite appreciation for handmade craftsmanship. Originally, ateliers were a private workshop or studio, and standard vocational practice for European artists in the middle ages. Until the 19th century, they housed artisans and painters, many of whom would train apprentices. Nowadays, ateliers are most closely associated with haute couture. This may not be too removed from the original use, considering fashion in itself is an art form.
Sensible, wearable and pragmatic clothes are what Casey Casey is best known for. Unconcerned with trends, they focus on creating work that can best be described as what they want to wear, or what they'd like to see be created. Becoming so removed from the system that creates the latest craze in your line of work may sound like a mistake, but this may be the very thing that has attained such success for Casey Casey.
Being aware of the trends while remaining impervious to their influence is a difficult feat. Being able to produce clothes that are unique is equally as challenging, but somehow Casey Casey has managed to do both. Their recipe to success is very similar to following the principles of good design, as they simply wish to create functional work that never goes out of style.
From the fabric in use to the shape of the garments, every aspect has been highly considered. There are a variety of textures at work in this collection, from sleek silk textiles to rough linen. The color palette is constrained to blue and yellow tones, with the occasional pop of orange. There are numerous patterns with variations in scale. Airy stripes sit among tightly laced liberty print, and mingle with textured and frayed orange and baby blue polka dots. Although the fact that there have been some French workwear inspirations within Casey Casey's work over time, this does not mean their work is typical. For every collared top, there are an equal amount of surprises that come in the form of drop crotch pants in silken textiles, button-ups with extreme drop shoulders, and flowing dresses in rough, yet wearable linen.
According to interviews with those who work at Casey Casey, their customers are often "filmmakers, architects or artists…people who understand well-made objects and want to be original," or those who "buy their clothes for decades, not seasons." Although there is no way to stereotype an entire client base, there is no denying that those who become enchanted with Casey Casey are people who appreciate thoughtful design that is as dependable as it is unique.


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Outfit Details:
Amazon Dress, Shoes & Bag
Sponsored by Amazon Fashion
We are now well into spring, with most of our days spent outdoors enjoying the sunshine and bountiful harvests from our ever-blooming garden. My wardrobe has taken a bit of a turn to more easy styles this week, including simple day dresses, slip-on shorts and skirts, loose linen blouses, and slide-on sandals and flats. My color pallet has taken a bit of a reprieve as well, with more muted beiges, blues, whites and greens in the forefront. That doesn't mean I'm shying away from adding pops of color here and there. It simply follows my mood, which was more melancholy as our family was recovering from a bug going around. The benefit was that I ended the week with a few new foundation pieces I had been missing. See below for my recent Amazon finds and visit our Amazon Storefront for an assortment of everyday styles to wear right now!
Striped Dress
This everyday blue and white striped shirt dress will become your favorite go-to for easy springtime dressing.
Leather Sandals
These slip-on sandals have a minimal look, making them the perfect choice to wear with just about any spring or summer style.
Straw Earrings
This popular woven earring style is both lightweight and neutral, making them comfortable and versatile choice, as well as a great gift option!
Amazon Dress, Shoes & Bag


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Ferrari 812 GTS 2021.
Ferrari 812 GTS: the most powerful production roadster in the world.
At a special event in early September two thousand nineteen, the Italians officially unveiled the Ferrari 812 GTS Roadster, which is an open version of the 812 Superfast.
At the front, the novelty differs from the latter only by the presence of two boomerang-shaped inserts in the upper corners of the windshield, designed to minimize aerodynamic noise. But the design of the rear of the car has changed much more.
Firstly, the characteristic influx of «hoods» appeared immediately behind the seats. Secondly, the brand specialists slightly changed the shape of the diffuser.
The retractable roof mechanism here is similar to other modern roadsters of the brand.
The folding / unfolding procedure of the hard top takes 14 seconds if the speed does not exceed 45 km / h. Interestingly, the rear window of the supercar is electric and can be lowered even with a roof over your head.
This solution will allow the driver and passenger to fully enjoy the sound of the technical «filling» of the model.
By the way, the latter on the Ferrari 812 GTS is similar to the 812 Superfast version. The roadster is powered by a 6.5-liter naturally aspirated V12 with 800 hp at 8,500 rpm and 718 Nm available at 7,000 rpm.
With such indicators, this model has become the most powerful production roadster in the world. Moreover, this is the first production Ferrari opener with a V12 in front in the last half century.
It takes a car 3.0 seconds to accelerate to hundreds (up to 200 km / h in 8.3 seconds), and the maximum speed reaches 340 km / h. The circulation of the new Ferrari 812 GTS is not planned to be limited, the price of the car has not yet been announced.
Beauty is in the details: Tuners from Novitec have refined the Ferrari 812 GTS.
In the nineteenth year, the specialists of the Novitec studio presented a modified version of the Ferrari 812 Superfast, and now the German masters have prepared a similar tuning kit for the open version of the 812 GTS.
Outside, the Italian dvuhdverka received a body kit made of «bare» carbon fiber, the components of which were pre-blown in a wind tunnel.
This body kit includes front flaps, a ventilated hood, inserts behind the front wheel arches, and other mirror housings.
In addition, the car received special wheels with central locking, which were developed in cooperation with the Vossen company.
We are talking about 21- and 22-inch wheels, which are «shod» in tires measuring 275/30 and 335/25 front and rear, respectively.
The tuners are ready to finish the interior of the model with high-quality leather and Alcantara, and the client can independently choose the color of the materials.
Provided and technical improvements Ferrari 812 GTS. The company proposes to increase the output of the 6.5-liter naturally aspirated V12 engine from the original 800 hp. and 718 Nm to 840 forces and 751 Nm of torque.
The installation of sports catalysts and a more efficient exhaust system will help achieve the desired result. By the way, the latter has 110 mm pipes and an adjustable damper here.
Unfortunately, it is not known how the dynamics of the supercar will change. Additionally, you can lower the two-door clearance by 35 mm and install a special hydraulic system.
Using a button in the cabin, the latter allows you to raise the nose of the car by 40 mm to drive «difficult» road sections, and when reaching 80 km / h, the electronics automatically lowers the suspension to the previous level. The cost of the listed improvements has not been specified.


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On November 26/27, 1778, a British expeditionary force weighed anchor off Sandy Hook, New Jersey and sailed southward for the purpose of recovering the Province of Georgia for the British crown. The war in the northern colonies had settled into a stalemate as the result of the disaster which had befallen royal arms at Saratoga. The details of the expedition's origin, progress, successes and partial failures are recounted faithfully and in depth in the pages which ensue. Lt. Col. Campbell's journal of the expedition, which includes the voyage from New York, his lightning-swift capture of Savannah and his two week occupation of Augusta is presented in print by the Richmond County Historical Society. Edited by Colin Campbell
$15.00 $5.00
Augusta Richmond County Historical Society, Inc.
2500 Walton Way, Reese Library at Augusta University
Augusta, GA 30904


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Sandusky, OH, USA — The Toledo Blade reports on Cedar Point's planned improvements to its hospitality operations:
"With its sprawling Breakers Hotel, pristine nationally-known beach, Atlantic City-style boardwalk "roller chairs," and shoreline rides like the Water Toboggan, the Cedar Point peninsula was crowded every summer with visitors anxious to spend lots of days and nights at the Erie County resort.
"Matt Ouimet thinks Cedar Point can be that way again.
"The Cedar Fair LP president and chief executive officer recently green-lighted a $60 million three-year reinvestment of hotel properties at the Sandusky-based amusement park chain's flagship Cedar Point property. If successful, the move could convince more visitors to plan multi-day stays at Cedar Point rather than one-day visits.
"The trio of company-owned hotels — the historic Breakers Hotel, upscale Sandcastle Suites, and 12-year-old Breakers Express hotel — at Cedar Point must become "more than a room for the night," Mr. Ouimet said.
"The former Walt Disney Co. executive said the importance of Cedar Point to its parent company is obvious.
"'It's more a destination resort or super regional park than any of the other parks we have. Its resorts play a much bigger role here than we would see at any of our other parks,' Mr. Ouimet said.
"'I was talking to some of our guests earlier about what they would like to see. They said they would like to see the resorts more refreshed and the beach enhanced,' he said.
"'I've become enamored with this place,' he said of the 106-year-old park. 'This is a very important asset not only to our company, but to the state of Ohio.'After 18 months at Cedar Fair's headquarters, which is nestled between Cedar Point's nostalgic buildings and beach and is but a short walk from the park's midway, Mr. Ouimet agrees with those customers who want a restoration of the park's hotel and beach properties.
"Mr. Ouimet envisions hotels with greater ambience — an aspect he may have learned from running Disney's Cruise Ship lines — and a beach where families can play, stroll, and bathe in the Lake Erie waters during breaks from the amusement park or nearby Soak City water park.
"To make that vision reality, two weeks ago Cedar Fair announced it would sell its Knott's Soak City water park in the San Diego suburb of Chula Vista to SeaWorld Parks & Entertainment. Cedar Fair will use the sale's proceeds to help fund makeovers at its Cedar Point hotels."


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On 10 and 11 September 2010 the Second General Assembly of the ELEN Association was held in Lyon. The three founding members of the ELEN Association were present: for Spain, the Conesa studio (Bufete Jurìdico Conesa & Asociados) with offices in Barcelona and Madrid; for Italy, the Carena studio (Studio Avvocato Carena) with offices in Turin and Milan; for France, the Duflos & Cartigny Associés – Europavocats studio (formerly D & RH-Avocats), with offices in Lyon and Paris.
During the 2009-2010 financial year, significant professional collaboration interventions were conducted in Italy thanks to the cooperation between Lyon and Turin.
During the 2010 General Assembly, a new integrated member was co-opted, the Valdemar Gonçalves & Associados studio in Oporto (Portugal) with the appointment of Valdemar Gonçalves Representative for Portugal and a new collaborating member, Studio Rimoldi of Buenos Aires (Argentina).
The ELEN Association aims to expand rapidly also in Germany, Switzerland, Austria, Belgium and the United Kingdom.


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Product description ※Please note that product information is not in full comprehensive meaning because of the machine translation.
Product Explanation ■ A pass case made of PU leather with a luxurious feel.
[Product Details]
Size : approx. 102 x 72 mm
Materials : PU leather
Specifications : with ball chain
(C) Ken Wakui kodansha / Animation "Tokyo Revengers" Production Committee
* As for used items, there may be some signs of wear, tear, or damage, but this does not affect the wearing or use of the item.


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Company SBB // Stefanie Batten Bland present "Look Who's Coming To Dinner" with Restart Stages at Lincoln Center
Company SBB // Stefanie Batten Bland
Save the Date! Mark your calendars for August 3rd.
As a part of Restart Stages at Lincoln Center—an outdoor performing arts center and space—Company SBB is thrilled to bring back Look Who's Coming To Dinner for the first time since October 2019, and be a part of the Restart Initiative.
Rapahël Cyril Segouin, Ryan Rouland Smith, Rachel Watson Jih, Annie Wang (under tablecloth) Claire Gieringer, and Latra Ann Wilson in "Look Who's Coming to Dinner." Photo by Carlos Cardona
Share Your Audience Review. Your Words Are Valuable to Dance.
Are you going to see this show, or have you seen it? Share "your" review here on The Dance Enthusiast. Your words are valuable. They help artists, educate audiences, and support the dance field in general. There is no need to be a professional critic. Just click through to our Audience Review Section and you will have the option to write free-form, or answer our helpful Enthusiast Review Questionnaire, or if you feel creative, even write a haiku review. So join the conversation.


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During the course of the Got-IT project, the Got-IT talks were the sessions in which experts talked on the topic of low eHealth literacy. They presented their views on the implications of low eHealth literacy and how we, as a community, can make sure that we design proper services. Did you miss one of the Got-IT talks? Don't worry! We have just released an eBook, summarizing their most valuable lessons.
You can download it here.


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industrial turnbuckles Haiyan is proved to be hugely popular in the market. Over these years, we have always been prioritizing customer satisfaction growth. We thus have developed Haiyan products that meet and exceed the customer expectation, with which we have achieved lower customer churn, and higher customer retention. The satisfied customers give our brand a positive publicity, helping increase our brand awareness. Our brand now holds important influence in the industry.
Haiyan industrial turnbuckles At Haiyan Ignition Coil, we take every customer requirement into serious consideration. We can provide samples of industrial turnbuckles for testing if needed. We also customize the product according to the provided design.stackable tool drawers,roller box tool,mechanic storage cabinets.


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Apple's iPad mini pricing: Did it miss the tablet death blow?
Apple's move to price the iPad mini at a starting price of $329 may preserve profit margins, but ultimately may cede some of the tablet market to the likes of Amazon and Google's Android army.
The $329 price tag was viewed as a negative development among a few analysts and tech observers on Twitter. Indeed, the $329 price for the iPad mini is tricky and appears to be designed to ensure iPad 2 sales are cannibalized instead of the latest version of the popular tablet.
Analysts were mixed on the iPad mini pricing. The general theme is that the iPad mini expands the total addressable market for Apple and strengthens its hammerlock on the tablet category. However, Apple could have delivered a death blow with a $299 price. Despite all the bluster about Google's Nexus 7, the price difference between the Android tablet and iPad mini makes the comparisons tricky.
More: Apple's iPad mini: it's all about price elasticity | With new iPads, Apple targets education opportunity | Google and Amazon can breathe a sigh of relief as Apple skips competing on price with iPad mini | Apple gets official with iPad mini; upgrades iPad again | Apple statement
Wall Street analysts made the following moves:
- First, iPad shipment estimates for the current quarter were cut.
- Many analysts said that refreshing the latest iPad so soon would alienate customers.
- And many expect the iPad mini to sell well.
What remains to be seen is whether Apple bet on a price tag of $329 for the iPad mini when it could have priced it at $299 and nailed the market. Morningstar analyst Brian Colello sums it up:
We're a bit disappointed at the starting price point of $329, as we fear that price-sensitive consumers may continue to turn to alternative tablet solutions, such as Amazon's Kindle Fire and Google's Nexus tablet at $200 price points...Apple could have strengthened its narrow economic moat by bringing more customers onto the iOS platform, as we believe that iOS customers who own multiple Apple products face higher switching costs and are less likely to shift to alternative platforms. Instead, the opposite scenario may play out. The risk around the mini, in our view, is that Apple's Mini pricing may concede more of the low-end tablet market to Amazon and Google, running the risk that these Android tablet users may buy compatible Android phones and/or shy away from Apple iPhones in the future.
Other Wall Street analysts were worried about the iPad mini price, but not by much. Piper Jaffray analyst Gene Munster said he thought consumer demand would still be strong.
Barclays analyst Ben Reitzes said in a research note:
We were hoping the mini could be priced at least a little lower given its competition is situated as low as $99, with many starting in the $199-$249 range. That being said, Apple seems convinced that consumers want the iPad and its ecosystem, which has worked so far at the high-end. We believe Apple can sell 5-10 million iPad mini's in the December quarter while cannibalization of the other iPads will likely run at 25-50%.
In the big picture, Apple, which is built to sell hardware at a premium, went with profit margins over worrying about the low end of the market. Time will tell if Apple missed a death blow, but with 100 million iPads sold the company can afford to take a few chances.


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The role of the ubiquitination-proteasome pathway in breast cancer: Applying drugs that affect the ubiquitin-proteasome pathway to the therapy of breast cancer
Breast Cancer Research volume 5, Article number: 1 (2002)
The ubiquitin-proteasome pathway is responsible for most eukaryotic intracellular protein degradation. This pathway has been validated as a target for antineoplastic therapy using both in vitro and preclinical models of human malignancies, and is influenced as part of the mechanism of action of certain chemotherapeutic agents. Drugs whose primary action involves modulation of ubiquitin-proteasome activity, most notably the proteasome inhibitor PS-341, are currently being evaluated in clinical trials, and have already been found to have significant antitumor efficacy. On the basis of the known mechanisms by which these agents work, and the available clinical data, they would seem to be well suited for the treatment of breast neoplasms. Such drugs, alone and especially in combination with current chemotherapeutics, may well represent important advances in the therapy of patients with breast cancer.
Function of the ubiquitin-proteasome pathway is essential for many fundamental cellular processes, including the regulation of receptor signaling pathways and the timely degradation of cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors during mitosis. In addition, ubiquitin-proteasome activity is necessary for antigen processing, angiogenesis, and apoptosis and for processing and degradation of misfolded and short-lived regulatory proteins such as transcription factors. This pathway consists of the ubiquitin-conjugating machinery (including an E1 ubiquitin-activating enzyme) and many E2 and E3 ubiquitin-conjugating and ubiquitin-ligase proteins (Fig. 1). The latter are responsible for transferring the activated ubiquitin moieties from E1 to specific sets of proteins, which are thereby targeted for degradation. It is the 26S proteasome, which contains the proteins responsible for proteolysis in a 20S core, that is responsible for degradation of these ubiquitinated products. Recent studies have also identified an increasing number of proteins that are subject to degradation through the 20S proteasome without prior ubiquitination.
The possibility of targeting the ubiquitin-proteasome pathway therapeutically was met in the past with skepticism, because of concerns that this approach would be inimical to life itself because of the important role played by the proteasome in normal cellular homeostasis. With the first demonstration that proteasome inhibitors were well tolerated and had activity in models of human malignancies in vivo[1], however, and the use in Phase I safety trials of inhibitors (such as PS-341 [2]) that showed acceptable toxicity with significant clinical benefit [3], targeting the ubiquitin-proteasome pathway for cancer therapy has become an area of intense investigation. This pathway may already play a major role in the therapy of patients with breast cancer who receive anthracyclines. For example, doxorubicin (Adriamycin) binds to subunits of the 20S proteasome, which then translocates to the nucleus [4], thereby acting as a carrier for this drug to exert many of its cytotoxic effects. Several other agents, however, influence either ubiquitination or proteasome-mediated degradation (Table 1), and can be divided into those that act indirectly, at steps prior to this pathway, or directly on some pathway component. This article will review the current status of these drugs, with a focus on their potential application to clinical care of breast cancer.
Drugs with indirect effects
Increasing ubiquitin-proteasome function
Several drugs that stimulate ubiquitin-proteasome pathway mediated degradation of a target protein in another disease have been evaluated in breast cancer. All-trans retinoic acid, an important step forward in the therapy of acute promyelocytic leukemia, may in part work by redistributing the promyelocytic leukemia-retinoic acid receptor oncoprotein, accelerating its proteasome-mediated degradation [5]. All-trans retinoic acid has been studied in patients with metastatic breast cancer and found not to have significant activity, but in combination with tamoxifen some responses were noted [6]. Whether these effects in breast cancer are mediated through an impact on the proteasome, however, is not known.
More clearly proteasome-related is the anticancer effect of the camptothecins, which block the religation step of the topoisomerase-1 (Top-1) reaction, and stimulate ubiquitination and subsequent proteasomal Top-1 degradation [7]. Several camptothecin derivatives have been studied in Phase I trials, and occasional responses in breast cancer patients have been noted. Although Phase II results have been generally disappointing, a recent study of irinotecan in patients with refractory metastatic breast cancer showed a 29% response rate, and tolerable toxicity [8].
Several interesting compounds under development are based on geldanamycin, which inhibits the ATPase activity of the heat shock chaperone protein HSP90. This leads to the degradation of client proteins via the ubiquitin-proteasome pathway, and since these include the c-erbB-2 (HER-2/neu) receptor protein-tyrosine kinase [9], their potential application to breast cancer therapy is clear. Analogues such as 17-allylamino-17-demethoxygeldanamycin are now in Phase I clinical trials.
Another agent in this category is the pure estrogen antagonist fulvestrant (Faslodex®), which has been approved for use by postmenopausal patients with estrogen-receptor-positive breast cancer who have progressed following other anti-estrogen therapy (reviewed in [10]). This drug appears to work in part by enhancing proteasome-dependent degradation of estrogen receptor α [11]. Since some estrogen agonists appear to have a similar activity with respect to estrogen receptor α [11], it would be interesting to determine if part of the well-known activity of tamoxifen and other hormonal agents is also due to a similar impact on the proteasome.
Inhibition of ubiquitin-proteasome function
Arsenic trioxide is an example of a drug that acts indirectly on the ubiquitin-proteasome pathway. It modifies a critical cysteine residue in the activation loop of the IκB kinase, preventing IκB phosphorylation. Subsequent IκB degradation is prevented, because degradation through the ubiquitin-proteasome pathway normally follows phosphorylation. Arsenic, therefore, indirectly inhibits NF-κB activation [12]. As detailed below, activation of NF-κB by chemotherapeutic agents and radiation is anti-apoptotic. In addition, arsenic has been reported to specifically inhibit expression and signaling through the estrogen receptor pathway [13]. Arsenic trioxide, therefore, may warrant further study in breast cancer either alone, or in combination with other agents, and a variety of Phase I and Phase II trials are underway.
Drugs with direct ubiquitin-proteasome effects
Drugs with targets other than the proteasome
All of the agents that have been noted to have a direct impact on ubiquitin- and proteasome-mediated proteolysis have been proteasome inhibitors. Since some of these were originally directed against other targets, they will be discussed separately from those which were designed to specifically inhibit the proteasome. In the former category are dietary compounds such as tannic acid [14], antiretro-viral agents including the HIV protease inhibitors [15, 16], and lipid-lowering agents, such as lovastatin [17], that inhibit the proteasome, although possible applications to breast cancer have not been investigated.
The immunosuppressive agent cyclosporine A is an uncompetitive proteasome inhibitor [18], but in the breast cancer setting it has been used predominantly to block cytochrome-P450-mediated drug resistance, or to induce graft-versus-host disease when patients have undergone high dose chemotherapy, followed by autologous bone marrow or peripheral blood stem cell rescue. Perhaps more interesting is another immunosuppressive, rapamycin, which inhibits expression of the proteasome activator PA28, and thereby inhibits proteasome function [19]. Since rapamycin blocks the estrogen-driven transition of breast cancer cells from the G1 to S phases of the cell cycle [20], further studies in breast cancer may be warranted.
Chemotherapeutic agents have been identified which inhibit the proteasome, including aclarubicin (aclacino-mycin A) [21], and vinblastine and vincristine [22], though it is unclear if, in the case of aclarubicin, this occurs at clinically relevant drug concentrations. Aclarubicin, an anthracycline derivative, has been evaluated in several Phase I and Phase II trials with generally disappointing results, though none were targeted towards breast cancer patients. The vinca alkaloid vinorelbine (Navelbine®), however, has well-documented activity in breast cancer [23], and it would be interesting to determine if this activity is a result of proteasome inhibition.
Proteasome-targeted drugs
Inhibitors of the proteasome were first synthesized two decades ago, and were initially used as laboratory tools to probe the proteolytic activities of this complex (reviewed in [24]) and its role in cellular processes. Subsequent investigations indicating these inhibitors were able to activate programmed cell death in a variety of human tumor-derived cell lines (reviewed in [25]) raised interest in such agents as possible cancer chemotherapeutics. Several lines of evidence suggest that proteasome inhibitors would be active agents in patients with breast cancer. From a mechanistic perspective, the transcription factor NF-κB, an important regulator of apoptosis, can be constitutively activated in several cancers, including some breast cancers (reviewed in [26]). As mentioned above, proteasome inhibitors work in part by blocking degradation of the inhibitory protein IκB, thereby decreasing NF-κB nuclear translocation [25]. Therefore, malignancies with high levels of activated NF-κB, such as breast cancer, should be especially sensitive to interruption of this pathway, which would induce tumor cell death.
A second, recently elucidated, mechanism by which proteasome inhibitors effect apoptosis is by decreased signaling through the p44/42 mitogen-activated protein kinase (MAPK) pathway [27]. High levels of expression of c-erbB-2 (HER-2/neu), and the homologous c-erbB-1, is a poor prognostic sign, and signaling from these receptors occurs in part through p44/42 MAPK. Furthermore, elevated p44/42 MAPK activity alone has been suggested to have prognostic significance for disease-free survival (reviewed in [28]), and therefore interruption of such signaling, such as by proteasome inhibition, would seem to hold promise for breast cancer therapy.
Proteasome inhibitors may also be effective in breast cancer treatment by helping to overcome some of the major pathways by which cancer cells resist the action of chemotherapy. Two of these have already been referred to above, in that both signaling through NF-κB and p44/42 MAPK can be anti-apoptotic. Chemotherapeutic agents such as taxanes and anthracyclines have been shown to activate one or both of these pathways, potentially limiting their own ability to induce tumor cell death. Since proteasome inhibitors block these pathways, they may be able to not only activate apoptosis, but also enhance the antitu-mor activity of drugs such as paclitaxel and doxorubicin.
Another important mechanism of resistance to chemotherapy is the expression by cancer cells of the P-glyco-protein, a membrane pump that promotes the efflux of xenobiotics such as chemotherapy drugs, decreasing their intracellular concentration and effectiveness. Proteasome function is necessary for normal maturation of P-glyco-protein. Proteasome inhibition could decrease the accumulation of P-glycoprotein in the membranes of cancer cells, thereby preventing it from ridding these cells of chemotherapy drugs, resulting in increased tumor killing.
Preclinical studies
Because of the promising rationale described above, a variety of proteasome inhibitors, most commonly based on short peptides, have been synthesized and evaluated using in vitro and in vivo model systems. The best studied of these in models of breast cancer, and in clinical trials as described below, has been Millennium Pharmaceuticals' bortezomib (Velcade™; previously known as PS-341, LDP-341, and MLN-341). This drug decreased the survival of both cultured MCF-7 cells derived from human breast cancer and of EMT-6/Parent mouse mammary carcinoma xenograft tumors in a dose-dependent fashion. PS-341 also increased the ability of radiation or cyclophosphamide to kill tumor cells in this model system [29].
In our laboratory we have been interested in combinations of PS-341 with anthracyclines, given the prominent role of the latter group of agents in breast cancer therapy. We have especially focused on liposomal doxorubicin, or Doxil®, because of this drug's activity in refractory breast cancer, its ease of administration (with dosing once every three to four weeks), and its favorable toxicity profile. Using a BT-474-based xenograft model of human breast cancer, we have found that the combination of PS-341 and Doxil® results in enhanced antitumor efficacy, and increased apoptosis when compared with that obtained using either agent alone (Fig. 2).
Clinical trials
More than 400 patients in the United States have been treated in Phase I and Phase II clinical trials of PS-341, which is given by intravenous push once or twice weekly. In the twice weekly for two weeks out of three schedule which has been used most often, the maximum tolerated dose in patients with solid tumors has been defined to be 1.3 mg/m2[30]. Because of significant activity against multiple myeloma seen in Phase I trials [3], Phase II [31] and Phase III studies of PS-341 are being pursued or planned for use against multiple myeloma. Preclinical data in chronic lymphocytic leukemia have also been encouraging, and Phase II trials of PS-341 are being pursued to treat this disease as well.
In Phase I studies of PS-341 as a single agent in patients with solid tumors, rare responses have been seen in cancers of the prostate, kidney, head and neck, and lung. Given its potential to enhance chemosensitivity, however, PS-341 is being combined with conventional agents in several ongoing Phase I studies. Some of these combination regimens hold promise for breast cancer treatment. For example, given the preclinical data supporting a Doxil®/PS-341 combination discussed above, a Phase I clinical trial of this combination is being conducted at the University of North Carolina at Chapel Hill. Similarly, a Phase I study of the combination of doxorubicin and PS-341 is ongoing at the University of Wisconsin [32]. The combination of paclitaxel and PS-341 is being studied at the Ohio State University (C Shapiro, personal communication). There are also currently ongoing Phase I trials of PS-341 in combination with 5-fluorouracil [33], irinotecan [34], and gemcitabine [35]. Preliminary data from these trial centers suggest that their respective combinations have been tolerated well so far. While all of these are Phase I studies that will enroll a variety of solid-tumor patients, at least some of the sites plan to focus on breast cancer patients, particularly once the maximum tolerated dose has been identified. This should enable preliminary evidence of antitumor activity to be obtained in this patient population in preparation for Phase II efficacy studies.
Future directions
Currently available drugs that most specifically target the ubiquitin-proteasome pathway, such as PS-341, focus predominantly on the proteasome itself. Research into the machinery responsible for ubiquitination has lagged somewhat in the past, but interest in this area has recently grown greatly. Inhibition of the E1 ubiquitin-activating enzyme would have effects on normal and neoplastic cells that would, in some ways, be even more broad-ranging than proteasome inhibitors. Drugs that would inhibit or stimulate specific E3 ubiquitin ligases, however, could have an impact upon a much more restricted set of proteins, and could be more specifically targeted and better tolerated clinically. One interesting potential target would be MDM2, which is overexpressed in some human breast tumors [36]. MDM2 is an E3 protein responsible for p53 degradation. Inhibition of MDM2 should result in increased levels of p53, prompting cell-cycle arrest, apoptosis, and possibly enhanced chemosensitivity in breast tumors with wild-type p53. Inhibitors such as these are currently being actively sought, and hopefully will soon be available for preclinical and clinical trials.
A second interesting target in this same light would be the F-box protein FWD-1, which mediates ubiquitination of the IκB α, β, and ε proteins [37]. Inhibitors of this component of the SCF(FWD1) complex would provide a more specific means of inhibiting NF-κB, and might sensitize cells to chemotherapy, as described earlier.
Finally, p27Kip1 could also be targeted. This cyclin-dependent kinase inhibitor is present at low levels in aggressive carcinomas. Its expression level, therefore, may have prognostic significance in breast cancer (reviewed in [38]). Since this protein is ubiquitinated by SCF(Skp2) in at least some phases of the cell cycle [39, 40], inhibition of this complex could result in accumulation of p27 and consequent cell-cycle arrest and apoptosis.
Ubiquitination could also be influenced by impacting upon related pathways, such as protein modification by the small ubiquitin-like modifier-1 (SUMO-1). SUMOlation of IκBα prevents its subsequent ubiquitination, thereby stabilizing its association with NF-κB [41]. Thus, stimulation of SUMOlation of IκBα could provide another mechanism of inhibiting nuclear NF-κB translocation and enhancing chemosensitivity. Interestingly, inhibition of SUMOlation may have some benefits as well, especially in combination with Top-1 inhibitors. Treatment of cells with camptothecin results in conjugation of Top-1 with SUMO-1, which is a possible repair response to topoisomerase-mediated DNA damage [42]. Thus, inhibitors of this repair mechanism may enhance sensitivity to agents such as irinotecan.
The ubiquitin-proteasome pathway is just beginning to be exploited as a target for cancer therapy. Nonetheless, given the available molecular biological, preclinical, and clinical data, there is very good reason to be optimistic that current drugs and future candidates will contribute significantly to the care of patients with breast cancer. Agents such as the proteasome inhibitor PS-341 are already undergoing clinical trials, and data concerning the Phase I safety and Phase II efficacy of combinations with other antineoplastic agents will be forthcoming over the next several years. This period should prove to be an exciting era for this field of research.
human immunodeficiency virus
mitogen-activated protein kinase
multidrug resistance
MAPK phosphatase
- NF-κB:
nuclear factor-κB
small ubiquitin-like modifier 1
- Top-1:
topoisomerase 1.
Orlowski RZ, Eswara JR, Lafond-Walker A, Grever MR, Orlowski M, Dang CV: Tumor growth inhibition induced in a murine model of human Burkitt's lymphoma by a proteasome inhibitor. Cancer Res. 1998, 58: 4342-4348.
Adams J, Palombella VJ, Sausville EA, Johnson J, Destree A, Lazarus DD, Maas J, Pien CS, Prakash S, Elliott PJ: Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res. 1999, 59: 2615-2622.
Orlowski RZ, Stinchcombe TE, Mitchell BS, Shea TC, Baldwin AS, Stahl S, Adams J, Esseltine DL, Elliott PJ, Pien CS, Guerciolini R, Anderson JK, Depcik-Smith ND, Bhagat R, Lehman MJ, Novick SC, O'Connor OA, Soignet SL: Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies. J Clin Oncol. 2002.
Kiyomiya K, Matsuo S, Kurebe M: Mechanism of specific nuclear transport of adriamycin: the mode of nuclear translocation of adriamycin-proteasome complex. Cancer Res. 2001, 61: 2467-2471.
Yoshida H, Kitamura K, Tanaka K, Omura S, Miyazaki T, Hachiya T, Ohno R, Naoe T: Accelerated degradation of PML-retinoic acid receptor α (PML-RARA) oncoprotein by all-trans-retinoic acid in acute promyelocytic leukemia: possible role of the proteasome pathway. Cancer Res. 1996, 56: 2945-2948.
Budd GT, Adamson PC, Gupta M, Homayoun P, Sandstrom SK, Murphy RF, McLain D, Tuason L, Peereboom D, Bukowski RM, Ganapathi R: Phase I/II trial of all-trans retinoic acid and tamoxifen in patients with advanced breast cancer. Clin Cancer Res. 1998, 4: 635-642.
Desai SD, Liu LF, Vazquez-Abad D, D'Arpa P: Ubiquitin-dependent destruction of topoisomerase I is stimulated by the anti-tumor drug camptothecin. J Biol Chem. 1997, 272: 24159-24164. 10.1074/jbc.272.39.24159.
Perez EA, Hillman DW, Mailliard JA, Ingle JN, Ryan JM, Fitch TR, Rowland KM, Kardinal CG, Krook JE, Kugler JW, Dakhil SR: Randomized phase II study of 2 schedules of irinotecan for patients with refractory metastatic breast cancer: an NCCTG Cooperative Group study [abstract]. Proc Am Soc Clin Oncol. 2002, 21: 52a-
Mimnaugh EG, Chavany C, Neckers L: Polyubiquitination and proteasomal degradation of the p185c-erbB-2 receptor protein-tyrosine kinase induced by geldanamycin. J Biol Chem. 1996, 271: 22796-22801. 10.1074/jbc.271.9.4974.
Robertson JF: ICI 182,780 (Fulvestrant) – the first oestrogen receptor down-regulator – current clinical data. Br J Cancer. 2001, 85 (Suppl 2): 11-14.
Preisler-Mashek MT, Solodin N, Stark BL, Tyriver MK, Alarid ET: Ligand-specific regulation of proteasome-mediated proteolysis of estrogen receptor-α. Am J Physiol Endocrinol Metab. 2002, 282: E891-E898.
Kapahi P, Takahashi T, Natoli G, Adams SR, Chen Y, Tsien RY, Karin M: Inhibition of NF-κB activation by arsenite through reaction with a critical cysteine in the activation loop of IκB kinase. J Biol Chem. 2000, 275: 36062-36066. 10.1074/jbc.M007204200.
Chen GC, Guan LS, Hu WL, Wang ZY: Functional repression of estrogen receptor α by arsenic trioxide in human breast cancer cells. Anticancer Res. 2002, 22: 633-638.
Nam S, Smith DM, Dou QP: Tannic acid potently inhibits tumor cell proteasome activity, increases p27 and Bax expression, and induces G1 arrest and apoptosis. Cancer Epidemiol Biomarkers Prev. 2001, 10: 1083-1088.
Liang JS, Distler O, Cooper DA, Jamil H, Deckelbaum RJ, Gins-berg HN, Sturley SL: HIV protease inhibitors protect apolipoprotein B from degradation by the proteasome: a potential mechanism for protease inhibitor-induced hyperlipidemia. Nat Med. 2001, 7: 1327-1331. 10.1038/nm1201-1327.
Piccinini M, Rinaudo MT, Chiapello N, Ricotti E, Baldovino S, Mostert M, Tovo PA: The human 26S proteasome is a target of antiretroviral agents. AIDS. 2002, 16: 693-700. 10.1097/00002030-200203290-00004.
Rao S, Porter DC, Chen X, Herliczek T, Lowe M, Keyomarsi K: Lovastatin-mediated G1 arrest is through inhibition of the proteasome, independent of hydroxymethyl glutaryl-CoA reductase. Proc Natl Acad Sci USA. 1999, 96: 7797-7802. 10.1073/pnas.96.14.7797.
Meyer S, Kohler NG, Joly A: Cyclosporine A is an uncompetitive inhibitor of proteasome activity and prevents NF-κB activation. FEBS Lett. 1997, 413: 354-358. 10.1016/S0014-5793(97)00930-7.
Wang X, Omura S, Szweda LI, Yang Y, Berard J, Seminaro J, Wu J: Rapamycin inhibits proteasome activator expression and proteasome activity. Eur J Immunol. 1997, 27: 2781-2786.
Pang H, Faber LE: Estrogen and rapamycin effects on cell cycle progression in T47D breast cancer cells. Breast Cancer Res Treat. 2001, 70: 21-26. 10.1023/A:1012570204923.
Figueiredo-Pereira ME, Chen WE, Li J, Johdo O: The antitumor drug aclacinomycin A, which inhibits the degradation of ubiquitinated proteins, shows selectivity for the chymotrypsin-like activity of the bovine pituitary 20 S proteasome. J Biol Chem. 1996, 271: 16455-16459. 10.1074/jbc.271.28.16455.
Piccinini M, Tazartes O, Mezzatesta C, Ricotti E, Bedino S, Grosso F, Dianzani U, Tovo PA, Mostert M, Musso A, Rinaudo MT: Proteasomes are a target of the anti-tumour drug vinblastine. Biochem J. 2001, 356: 835-841. 10.1042/0264-6021:3560835.
Romero A, Rabinovich MG, Vallejo CT, Perez JE, Rodriguez R, Cuevas MA, Machiavelli M, Lacava JA, Langhi M, Romero-Acuna L: Vinorelbine as first-line chemotherapy for metastatic breast carcinoma. J Clin Oncol. 1994, 12: 336-341.
Orlowski M, Wilk S: Catalytic activities of the 20 S proteasome, a multicatalytic proteinase complex. Arch Biochem Biophys. 2000, 383: 1-16. 10.1006/abbi.2000.2036.
Orlowski RZ: The role of the ubiquitin-proteasome pathway in apoptosis. Cell Death Differ. 1999, 6: 303-313. 10.1038/sj.cdd.4400505.
Orlowski RZ, Baldwin AS: NF-κB as a therapeutic target in cancer. Trends Mol Med. 2002, 8: 385-389. 10.1016/S1471-4914(02)02375-4.
Orlowski RZ, Small GW, Shi YY: Evidence that inhibition of p44/42 mitogen activated protein kinase signaling is a factor in proteasome inhibitor-mediated apoptosis. J Biol Chem. 2002, 277: 27864-27871. 10.1074/jbc.M201519200.
Dickson RB, Lippman ME: Growth factors in breast cancer. Endocr Rev. 1995, 16: 559-589. 10.1210/er.16.5.559.
Teicher BA, Ara G, Herbst R, Palombella VJ, Adams J: The proteasome inhibitor PS-341 in cancer therapy. Clin Cancer Res. 1999, 5: 2638-2645.
Aghajanian C, Soignet S, Dizon DS, Pezzulli S, Daud A, Spriggs DR, Adams J, Elliott P, Pien C: A Phase I trial of the novel proteasome inhibitor PS-341 in advanced solid tumor malignancies [abstract]. Proc Am Soc Clin Oncol. 2001, 20: 85a-
Richardson PG, Barlogie B, Berenson J, Traynor A, Singhal S, Jagannath S, Irwin D, Rajkumar V, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski RZ, Kuter D, Limentani S, Esseltine D, Kauffman M, Adams J, Schenkein D, Anderson KC: Phase II study of the proteasome inhibitor PS-341 in multiple myeloma patients with relapsed/refractory disease [abstract]. Proc Am Soc Clin Oncol. 2002, 21: 11a-
Thomas JP, Arzoomanian R, Alberti D, Geiger P, Marnocha R, Tutsch K, Dresen A, Volkman J, Binger K, Kolb M, Feierabend C, Black S, Hampton K, Wilding G: A phase I and pharmacodynamic study of the proteasome inhibitor PS-341 in combination with doxorubicin [abstract]. Proc Am Soc Clin Oncol. 2002, 21: 93a-
Iqbal S, Lenz HJ, Groshen S, Wei Y, Gandara DR, Lara PN, Gumerlock P, Doroshow JH, Twardowski P, Synold T: Phase I study of PS-341 in combination with 5-FU/LV in solid tumors [abstract]. Proc Am Soc Clin Oncol. 2002, 21: 93a-
Clark JW, Ryan D, Dees C, Eder JP, Winkelmann J, Lynch T, Supko J, Appleman LJ, Fidias P, O'Neil B, Orlowski RZ, Baldwin A, Kinchla N, Zhu A, Esseltine D, Elliott P, Adams J, Kauffman M, Schenkein D, Cusack J: Phase I dose-escalation study of the proteasome inhibitor, PS-341, plus irinotecan in patients with advanced solid tumors [abstract]. Proc Am Soc Clin Oncol. 2002, 21: 93a-
Ryan DP, Eder JP, Winkelmann J, Lynch T, Supko J, Appleman LJ, Fidias P, Enzinger P, Zhu A, Kinchla N, Esseltine D, Baldwin A, Elliott P, Adams J, Kauffman M, Schenkein D, Cusack J: Pharmacokinetic and pharmacodynamic phase I study of PS-341 and gemcitabine in patients with advanced solid tumors [abstract]. Proc Am Soc Clin Oncol. 2002, 21: 95a-
Bueso-Ramos CE, Manshouri T, Haidar MA, Yang Y, McCown P, Ordonez N, Glassman A, Sneige N, Albitar M: Abnormal expression of MDM-2 in breast carcinomas. Breast Cancer Res Treat. 1996, 37: 179-188.
Shirane M, Hatakeyama S, Hattori K, Nakayama K: Common pathway for the ubiquitination of IκBα, IκBβ, and IκBε mediated by the F-box protein FWD1. J Biol Chem. 1999, 274: 28169-28174. 10.1074/jbc.274.40.28169.
Chiarle R, Pagano M, Inghirami G: The cyclin dependent kinase inhibitor p27 and its prognostic role in breast cancer. Breast Cancer Res. 2001, 3: 91-94. 10.1186/bcr277.
Podust VN, Brownell JE, Gladysheva TB, Luo RS, Wang C, Coggins MB, Pierce JW, Lightcap ES, Chau V: A Nedd8 conjugation pathway is essential for proteolytic targeting of p27Kip1 by ubiquitination. Proc Natl Acad Sci USA. 2000, 97: 4579-4584. 10.1073/pnas.090465597.
Hara T, Kamura T, Nakayama K, Oshikawa K, Hatakeyama S: Degradation of p27(Kip1) at the G 0-G1 transition mediated by a Skp2-independent ubiquitination pathway. J Biol Chem. 2001, 276: 48937-48943. 10.1074/jbc.M107274200.
Desterro JM, Rodriguez MS, Hay RT: SUMO-1 modification of IκBα inhibits NF-κB activation. Mol Cell. 1998, 2: 233-239.
Mao Y, Sun M, Desai SD, Liu LF: SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage. Proc Natl Acad Sci USA. 2000, 97: 4046-4051. 10.1073/pnas.080536597.
Glickman MH, Ciechanover A: The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev. 2002, 82: 373-428.
Jesenberger V, Jentsch S: Deadly encounter: ubiquitin meets apoptosis. Nat Rev Mol Cell Biol. 2002, 3: 112-121. 10.1038/nrm731.
Frankfurt OS, Krishan A: Identification of apoptotic cells by formamide-induced DNA denaturation in condensed chromatin. J Histochem Cytochem. 2001, 49: 369-378.
The authors would like to acknowledge support from the Department of Defense Breast Cancer Research Program, BC991049, the Leukemia and Lymphoma Society, R6206-02 (to RZO), from the National Cancer Institute SPORE in Breast Cancer (to RZO and ECD), and from the Doris Duke Charitable Foundation (to ECD).
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Orlowski, R.Z., Dees, E.C. The role of the ubiquitination-proteasome pathway in breast cancer: Applying drugs that affect the ubiquitin-proteasome pathway to the therapy of breast cancer. Breast Cancer Res 5, 1 (2002). https://doi.org/10.1186/bcr460
DOI: https://doi.org/10.1186/bcr460


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QBN Sessions
Living in London rocks. Except sometimes. Like now. Because it means we can't go to the first QBN Session, from the folks behind Newstoday, which takes place on 7 September at the Getty Centre in Los Angeles.
Shepard Fairey, Joshua Davis, Phunk Studio, Michael C. Place (isn't he just everywhere right now?), Michael Muller, The Mill and Matt & Mark Owens will be sharing the wisdom. It's $240 for a ticket, but you get a gourmet lunch box and two drinks tickets.
We're, like, totally bummed not to be there.


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An absolute must! Hvar is one of the ten most beautiful islands in the world and is the fourth largest island in Croatia.
The island is not only particularly popular with holidaymakers and active holidaymakers, but also with friends of good taste.
Picturesque bays, turquoise waters and secluded pebble beaches invite you to cozy hours in the sun. you awaits in addition to the many natural beauties, many exciting cultural and historical sights.
Attractions / Highligts
- Spanjola fortress
- St. Stephen's Cathedral
- Franciscan monastery
- Benedictine monaster


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Museum of Scottish Country Life
Project Overview
project name: The Museum of Scottish Country Life, Kittochside
quantity surveyor: Thomas and Adamson
client: Partnership between The National Museums of Scotland and The National Trust for Scotland
services consultant: Harley Haddow Partnership
value: £550K
structural engineer: Harley Haddow Partnership
architect: Page and Park
main contractor: Skanska
The Museum of Scottish Country Life shows how country people lived and worked in Scotland in the past and how that has shaped the countryside of today.
Taylor and Fraser's involvement within the overall project, which cost over £9,000,000, included mechanical services for wide ranging spaces such as the exhibition areas, gift shop, restaurant, kitchen, administration and storage areas.
Scope of Work
The Mechanical Services installation comprised:
- Gas fired LTHW boiler plant serving radiators, heat emitters and coils within air handling units
- Air handling units providing supply and extract ventilation throughout the building including exhibition areas
- Flue dilution system
- Full BMS to provide integrated control of the mechanical services


text:
Darlene M. Cartier earned a Bachelors of Environmental Studies from the UNLV in 1997. She went on to work for the Southern Nevada Water Authority managing residential water conservation programs. In 1999 she attended the UNLV William S. Boyd School of Law. During Law School she was a member of Boyd's Moot Court Competition Team for two years.
Ms. Cartier was admitted to practice law in Nevada in 2004. She is admitted to practice throughout all Courts in the State of Nevada, including the United States District Court for Nevada. Her practice has focused on litigating and resolving complex matters on behalf of insurance carriers, corporations and individuals, including business and commercial disputes, complex multi-party tort litigation, construction defect litigation, contract disputes, subrogation actions, as well as the defense of class action, products liability, personal injury and general liability claims.
Ms. Cartier grew up in an Air Force family and has lived all over the world. She enjoys traveling, spending time with her family, boating and camping.


text:
Souhan; Twins Could Choose to Trade Berrios [PODCAST]
The Twins lost 4-1 at home to the Chicago White Sox Tuesday night to even the series 1 game apiece heading into today's rubber game. Star Tribune Sports Columnist Jim Souhan joined me on WJON today. He says if the Twins feel Jose Berrios will cost them more money that what they can afford they may look to trade him before the trade deadline this month. Souhan says Berrios could bring them a haul in prospects and he may be the most valuable player the Twins could trade at the deadline. Berrios is 7-3 with a 3.36 ERA in 17 starts this season. He started last night's game and allowed just 1 earned run in 7 innings with 10 strikeouts for Minnesota.
The Gopher men's basketball team announced that Eric Curry will play this season and forego the job as a graduate assistant coach for at least this next season. The 6'9 power forward missed 2 seasons due to severe knee injuries and will be taking advantage of the additional year of college eligibility athletes have been granted due to the pandemic. Jim Souhan says Curry will help this team but doesn't change the fact that this is a rebuilding team that most likely won't compete for a NCAA tournament berth in 2021-2022. Souhan says head coach Ben Johnson will likely have 3 years to see how improved the team can get.
The Minnesota Lynx re-signed guard Rachel Banham. Souhan says that was the plan all alone. He says the Lynx have done something similar with other players this season as well.


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2021 FAQs – The BMJ Awards
Eligibility criteria
- The Awards are open to UK healthcare teams only and the project needs to be based in the UK
- Individuals and teams can participate
- Your project must be clinically-led
- The initiative/project had to be active in 2020
- Each project may only be entered once, and individuals/teams can only enter one project per category. If you have an additional project that you would like to enter for another category this is allowed.
See the full terms and conditions.
When is the closing date for The BMJ Awards 2021 submissions?
The final closing date for all submissions has been extended for The BMJ Awards 2021 and is now Monday, 21 June 2021.
You can view all our key dates here.
How much does it cost to enter?
Entries are free of charge. An optional Benchmark Report is available for £40 + VAT for all categories except the Outstanding Contribution to Health and Research Paper Categories. If you purchased a Benchmark Report, you will receive this 2 weeks after The BMJ Awards virtual ceremony.
Where do I enter my submission?
You can start your submissions using our online entry form. Once you have completed all sections simply submit it. You will then receive an email confirming your submission has been received.
Do I need to complete an entry form, and where do I get it from?
Yes, you must complete the official entry form to enter The BMJ Awards. It can be downloaded after you create your profile and log in here
How do I submit my entry?
-Log into your submission here
-Download and complete your entry form.
-Please select the category you would like to enter by clicking 'Enter This Category' and have your completed entry form ready to upload.
-Complete your entry details (including your Team and Project Name), and click 'Upload' to add your completed entry form.
-Make sure you select 'Save and return to awards summary'
-If you would like to enter more categories, click 'Enter Category' and repeat the steps above.
-Select the entries you would like to submit by clicking the box on the right-hand side, and select 'Submit'.
-The final step is to click 'Complete registration'.
-You will then receive an email confirming your successful entry to the 2021 BMJ Awards.
How do I know my submission has been received by The BMJ Awards team?
You will receive a confirmation email after you have successfully uploaded your entry form and supportive documents, selected your category and hit submit.
See 'Where do I enter my submission?' in these FAQs for a full step by step breakdown on how to submit your BMJ Awards entry
What is the judging process for The BMJ Awards
The 2021 judging process will take place in a virtual format. You can find out more about the judging process here.
What are the categories for 2021?
We have seventeen categories for The BMJ Awards 2021, including two Special Recognition Awards for Outstanding Contribution to Health and UK Research Paper of the Year.
Read more at: https://thebmjawards.bmj.com/2021-categories/
What does the submission process include?
The online entry process will take no longer than 20 minutes. You will need to answer up to 10 questions about your project and you will have an opportunity to add supporting documents (note: there is a limit to the supplementary documents that can be uploaded).
How long do I have to make my submission?
You can start the process and come back to complete your submission anytime before midnight Monday, 21 June 2021, however, we encourage you to send your entries in as soon as possible.
When will I know if I've been shortlisted?
If you are shortlisted for an award, you will be contacted by The BMJ Awards team who will invite you to the virtual judging session and explain further about the process and how to prepare for your judging session. You will be asked to provide some further information and photos of your team. You will also be contacted by a journalist who will be writing a feature for The BMJ.
How is the judging carried out?
Once all the shortlisted teams have been announced, you will be invited to attend a virtual judging session in September. You will have the chance to meet virtually with the judging panel, comprising a BMJ champion and three expert judges, one of whom is a patient representative, to present your project and answer any questions from our judges.
Take a look at our key dates.
What is the judging criteria?
Judges will be interested in the scale of the problem that your project is addressing, the impact of the project, and whether the project took an innovative and original approach. They will also be looking at the size of the benefit your project produced, what you learnt from this experience, how much it cost, and the potential for wider application. As The BMJ is seeking to advance partnership with patients, we are also asking entrants to describe how they included patients in the design and evaluation of their projects.
When do I find out if I have won?
All winners will be announced at The BMJ Awards virtual ceremony on Wednesday, 29 September 2021.
When and where is The BMJ Awards ceremony?
The BMJ Awards will take place on Wednesday, 29 September 2021 as a fully virtual awards ceremony.
Is there a cost to attend The BMJ Awards ceremony?
There is no cost to attend and we encourage as many of your teams, colleagues, and contacts to join us in the evening when we announce the winners.
You'll be able to register for the virtual ceremony to ensure that you receive a save the date invitation to join us virtually on the night to watch the ceremony, at home, or in your workplace.
What do we receive for winning or for being shortlisted?
The winning team in each category will receive a trophy and winner's certificate. All shortlisted teams will receive a finalists' certificate.
All winners are also showcased in The BMJ, one of the oldest general medical journals in the world.
Can I nominate a colleague to enter the BMJ Awards?
If you know of someone that is working on an innovative project that should enter The BMJ Awards please enter their details in this form and a member of The BMJ Awards team will contact them with details on how to enter.
We will continue to monitor the situation over the coming months, being mindful of our duty of care to all involved. Following ongoing reviews, should we need to re-assess and adapt the BMJ Awards, we will provide updates on any changes.
Can I submit an application or nominate someone for the UK Research Paper of the Year Award or Outstanding Contribution to Health Award?
The judging for the UK Research paper of the year award and Outstanding contribution to health award is carried out by the editorial team at The BMJ, and is an editorial decision based on publications and projects that the editors have seen over the past year. It is therefore not possible to submit an application or nominate an individual for these awards.


text:
Designed to die: towards an architecture of impermanence
Shafique, Tanzil and Mejias Villatoro, Paco (2017) Designed to die: towards an architecture of impermanence. STUDIO: Ephemeral, 12. pp. 96-105. ISSN 2240-4767
Full text not available from this repository.Abstract
In a recent lecture, Peter Eisenmann lamented the loss of authority of the architect——the loss of a standard by which to make judgements in architecture. Reflecting on that, we wondered if this loss propagates from the burning question put forward by Derrida in his 'Letter to Peter Eisenmann', where he asked what might bring architecture back to "the experience of its own ruin (death)?". Discarding such questions, architectural discourse centers around creativity and durability. An inherent natalism invigorates architecture that, when faced with the question of its own demise, recoils from such perversions. The 'firmitas' from Vitruvius still resonates as a futile pursuit of permanence. Architectural practice does not, on the large, address the questions of decay, ruination and demise other than to utilize these concepts against which technological innovation is developed and deployed. Montaigne quotes Cicero in his Essays that to philosophize is to learn how to die. We argue that the failure of current architectural theory, as Eisenmann thankfully alludes to, is not due to the lack of instrumentality in bringing architecture to life, but rather, stems from its failure to account for death. Such an investigation is not to show the impotence of architecture but rather to reclaim the dissolution of architecture as a new territory of design. Tracing the history of traditional and modern architecture, we find strong reasons to believe that ephemerality is the normative condition and permanence an illusion. Beyond providing typological and representational frameworks that tackle the issue of death, we wish to stress why any design philosophy must provide an eschatology of architecture, given the civilization-at-risk in the Anthropocene. In such a time, to be ephemeral is to embrace death with authority.
Item Type: | Article |
Uncontrolled Keywords: | architecture, impermanence |
Subjects: | B Philosophy. Psychology. Religion > BJ Ethics H Social Sciences > HM Sociology N Fine Arts > NA Architecture |
Divisions: | Faculty of Arts, Business & Applied Social Science > Department of Arts & Humanities |
Depositing User: | Paco Mejias villatoro |
Date Deposited: | 23 Jun 2021 14:52 |
Last Modified: | 23 Jun 2021 14:52 |
URI: | https://oars.uos.ac.uk/id/eprint/1854 |
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US Sues G-d For Monopoly Of The Universe
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US Sues G-d For Monopoly Of The Universe
US Sues G-d For Monopoly Over the Universe
by Ben Oren
Yesterday, in an effort to bring more choice to human beings in their
pursuit of spirituality and everythingness, the United States Department
of Justice and the Free-Trade Commission took the first step to curb
G-d's monopoly on the universe by enforcing America's anti-trust laws
and taking Yahweh all the way to the Supreme Court.
After receiving several complaints from prospective supreme beings whose
hopes for entering the divine creator industry had been preemptively
aborted by the "Big Man" himself, U.S. Attorney General Janet Reno began
investigations into G-d's business practices and His company, Infinity
Plus One Inc.
According to industry experts, G-d began his company with only
supernatural powers and a dream. He was a child prodigy who mastered
His technical skills in creation at an early age and by the time He was
only 19 He had dropped out of college and gathered up the capital to
begin Infinity Plus One Inc. After two years G-d turned a profit, and
after some 5700 years many corporate insiders would say he had cornered
the industry as well.
Preliminary findings by the government have unearthed shady business
dealings by G-d to quell any potential competition from others. James
Milton experienced the wrath of Infinity Plus One last year when he made
his own attempt to jump into the burgeoning god market. However, what
he found soon pushed him back into his old profession -- Assistant
Bowling Shoe Attendant at Lots-O-Bowl in Piscattaway, NY. "When I heard
about the money a guy could make in starting a god business I was like,
'I need to try this.'"
However, soon afterwards Mr. Milton experienced some of G-d's hardball
tactics. At first he just received a few subtle messages, like the time
he saw a burning bush in his backyard, or the time Lot's wife turned to
salt. But when he did not heed these warnings, G-d became a bit more
aggressive in his attempt to prevent Milton's "Gods-R-Me" Industries from
coming into existence.
"One day I was eating lunch," says Milton, "going over some plans with
my consultants, when all of a sudden boils popped up all over our
bodies. I thought nothing of it, until I returned home and my first
born son was dead. That's when I decided that it was in my best
interest not to screw around with G-d."
Similarly unethical, and potentially unlawful, business practices by
Infinity Plus One Inc. have sprung up since the initial suit was filed.
Coming out of the Supreme Court, G-d was reticent and forwarded all
questions to his dream team of lawyers, which is headed by Johnnie
Cochran. In a press conference following the first day of testimony,
Cochran declared, "The United States Government has nothing on my
client. G-d is a good and benevolent man. He is a man who made the
universe in six days and can end it in a nanosecond. That's not a
threat. That's just the facts. So if you don't want to burn in
hell-fire, this case must expire!"
Rounding out G-d's legal advisory committee are Moses, King Solomon,
Jesus of Nazareth, Mohammed, and William Jennings Bryan.
Reno retorted, "Just because this man is above time does not mean he is
above the law. We believe we do have a case against Mr. Yahweh and we
shall pursue it with the utmost care, well within both our rights as the
government and His rights as G-d."
The Department of Justice believes it has a solid case against Jehovah
citing the past legal ruling of New Jersey v. Zarathustra (1974) in
which the state of New Jersey sued Satan and his company, Disney Inc.,
for their monopoly of Hell.
Yesterday's testimony came to a standstill in a bizarre turn of events
when God refused to swear on the bible and instead chose to swear on
himself. When U.S. attorney Tom McDamd objected, a lighting bolt
suddenly hit him in the face, causing Chief Justice William Rehnquist to
dismiss the session until the following day.
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text:
The package describes this treat as "Choco Crunch and Vanilla Ice", I'm not sure what that means but I sure hope it means something good. The first good sign of this treat is the fact that the "Crunch" is not just peanuts. Instead is appears to be some kind of crunchy crumbled up cookie coating. I'm glad, because I've eaten many peanut covered ice creams in my day and the change is nice. It's not that I hate the peanut coating I just love creativity.
Having said that, I have had cookie bits on the outside of an ice cream bar before, it's just these are a little different. Maybe it's because they seem to be really crunchy, unlike other cookie outsides that are more often soggy. Maybe I just got a really fresh one of these or maybe they've found the way to keep the crunch for longer. Either way it really is a nice texture.
The ice cream is pretty generic, but that's ok, because I think it should just help the rest of the treat along in this case. The chocolate on the other hand is a little disappointing, it just doesn't add anything other than hold the cool little crunch bits onto the ice cream a little better. It would be nice to try this with a higher quality chocolate is all I'm saying.


text:
Sunset #4 This is a post on the process I have gone through to catalogue and tag my images. Instead of focusing on a few specific images I thought it would be good to reflect on how the cataloguing of the images has been changed on our site over the last 6 months. Initially the images were catalogued by name, but when we came to having a series of sunsets calling them sunset and sunset #1 etc .. sunset #5 etc things began to get a bit confusing. So we changed to giving the images reference numbers. Initially the reference number was allocated randomly, as they were added to the system. This is fine for a computer, but not really much good for humans. Sunset #5 Say the images have ref 100 (Landscape Collection), 101 (Plants Collection), 102 (Human Collection), 103 (Plants Collection) .. 159 (Landscape Collection), 160.. etc. The trouble with this was that now a human has no idea that image 159 comes after image 100 and rapidly caused considerable confusion. Sunset #6 So it was decided to allocate 1000 values to the left of the decimal and 9999 to the right to each collection type, as a reference. Potentially allowing 19999 images per collection!! This should more than cover future needs. Having worked out a reference system that was fit for purpose as the saying goes. The aim was to add this to the system. Rather than having it in a data base, it was decided to use an XML data file, as it is lightweight and easy to store and handle data. Each web page reads the small XML data file and extracts all the relevant data required about that specific image, or image collection, or tag, location, date taken etc. In fact anything relevant can be stored against the reference in the XML file and read by the web page so long as it knows what it is looking for. Scottish Flag in the Sky Whilst doing this at the same time I was committed to having a certain number of pages up and running by a specific date. This lead to a dilemma as it was quicker to put up the simple pages that did not need all the XML data, for example the tag and location data. So in the end around 140 pages went up without the complete XML data. Having met the deadline, all the new pages from then on have full XML data and I am now going back and adding the extra data for the pages that went up without it. Sycamore Gap Hadrians Wall Now as around a third of the images have a full data compliment added we have made live the page where they can be selected by tag Of course this now raises a further dilemma as I need to go back and add the extra data for all the images that did not get the full deal first time round, and offset that against adding new images, like these latest images, which is a far more enjoyable activity. I have set myself a task of doing so many each week, with the aim of trying to be complete by the end of the year. We shall see if I make it. (Also this could well mean that my sunset names change, but we will have to wait and see until I get to them) Leave a Reply. |
Tim Fuller
Dyslexic doodles on photography, food (growing, cooking & of course eating), faith and other fascinating things. This is a personal blog expressing my views. Archives
November 2015


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Love, love this Christmas line and I was sure to buy as much as I think I will need right away as I knew others would feel the same! Beautiful colors, wonderful drawings on quality paper, as you would expect from G45. I just ordered another 8x8 pad as someone asked me to do a book for them after they saw the line.
Beautiful bright colors and great paper quality. Love the Santa with the sack of toys. The only problem with Graphic 45 paper is I sometimes hate to use it because it's so pretty and if I use it then it's all gone!! Silly I know, but I love Graphic 45 designs.
Every page is awesome.
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Air Superiority
I believe Holy Spirit is saying to us that the prophetic prayer movement has gained "air superiority." Spiritually, we have broken through to the point where we can now control things because of the breakthroughs we've achieved in the spirit realm. We must keep praying to maintain our air superiority. There are two significant timings for this breakthrough. Awaken the Dawn and Rise Up, that Lou Engle and others are planning in D.C., October, 6th – 9th, is a huge part of this. On February 22nd, we will gather there again for a new wave of the Appeal to Heaven movement, and a new season will be launched.
"The key of the house of David I will lay on his shoulder; so he shall open, and no one shall shut; and he shall shut, and no one shall open." (Isaiah 22:22; NIV)
Give Him 15 minutes in prayer:
Thank the Lord for the air superiority that we have gained after so many years of intercession.
Thank Him for the maturing of the Body of Christ into the Ekklesia of God.
Pray for the events that are coming that we believe can solidify these victories we have won – Awaken the Dawn, Rise Up and the upcoming next phase of the Appeal to Heaven
Plan to attend at least one of the above events.
A prayer you can pray:
Father, we thank you that we have gained air superiority in this nation. The Church has gained air superiority! Our prayers have been effective. The fasting, the worship, the crying out, the solemn assemblies, Lord, for the last 25 to 30 years, have been effective. Lord, we thank you for the greatest air weapon in the history of mankind – the Ekkelsia. The enemy has tried to rip and tear and destroy what You had planned for America. You are raising up more opportunities for the praying Church to come together to enforce the air victory! Bring us together under Your banner, Jesus. Amen.
Today's decree:
I decree that the Ekklesia will keep praying, so that we maintain our air superiority in this critical stage in our nation.