text:
I have not seen this specific issue elsewhere in this forum. The Promotion Slider advertises "multiple rotating ad zones." I tried to implement two sliders each calling different categories. My result was that the sliders would end up using slides from both categories in each slider.
Am I missing a step or have others had the same result?
Thanks, Ian


text:
'If I Feel' loafer
Out of stock
Unfortunately this item is out of stock
Black patent leather loafer from Hego's featuring a round toe, a triple tonal grey sole, all-over silver-tone studding and a studded fringe section at the front.
Made in Italy
Designer Style ID: IFIFEELNERO
Farfetch ID: 10264360
- Sole Composition:
- rubber 100%
- Outer Composition:
- Patent Leather 100%
Your order will be shipped directly from the boutique to you. Farfetch ships worldwide, and you will be able to track your order at any time. The cost of shipping your order will be calculated at the checkout.
Import duties information
Delivery duties are included in the item price when shipping to all EU countries plus USA, Canada, China, Australia, Puerto Rico, Switzerland, Singapore, Republic Of Korea, Kuwait, Qatar, India, Norway, Saudi Arabia, Taiwan, Thailand, U.A.E., Japan.This means all import duties are included in your order, so the price you see is the price you pay. You will not receive an additional duty bill from the courier to receive your shipment. If you are ordering from within your own customs zone or country, import duties will not be applicable anyway, however you may have to pay VAT or local Sales Taxes where applicable (for the UK and USA these are included at the checkout).
Delivery duties are not included in the item price when shipping to all other countries. This means you may be liable to pay import duties on receipt of your order.
Free returns pick-up
You have 14 days from receiving your order to return the item to the boutique using our free returns pick-up service. We strongly recommend that you book your free returns pick-up within 7 days of receiving your order to ensure that it arrives back to the boutique in time. Please note for standard orders we can only collect returns from the same country to which your order was delivered. For click and collect orders we can collect your return from the country your order was delivered to and also the country of the original boutique you ordered from. Click here to read our full returns policy.

subset: commoncrawl


text: QSpace Collection: http://hdl.handle.net/1974/811 2016-08-25T15:03:15Z The differential impact of oxytocin receptor (OXTR) genotypes on the risk of autism spectrum disorder (ASD) and resulting social communication deficits http://hdl.handle.net/1974/14715 Title: The differential impact of oxytocin receptor (OXTR) genotypes on the risk of autism spectrum disorder (ASD) and resulting social communication deficits Authors: Milton, MEAGAN Abstract: Background: Autism spectrum disorder (ASD) is multifactorial and is likely the result of complex interactions between multiple environmental and genetic factors. Recently, it has been suggested that each symptom cluster of the disorder, such as poor social communication, may be mediated by different genetic influences. Genes in the oxytocin pathway, which mediates social behaviours in humans, have been studied with single nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR) being implicated in ASD. This thesis examines the presence of different oxytocin receptor genotypes, and their associations with ASD and resulting social communication deficits. Methods: The relationship between four OXTR variants and ASD was evaluated in 607 ASD simplex (SPX) families. Cases were compared to their unaffected siblings using a conditional logistic approach. Odds ratios and associated 95 percent confidence intervals were obtained. A second sample of 235 individuals with a diagnosis of ASD was examined to evaluate whether these four OXTR variants were associated with social communication scores on the Autism Diagnostic Interview – Revised (ADI-R). Parameter estimates and associated 95 percent confidence intervals were generated using a linear regression approach. Multiple testing issues were addressed using false discovery adjustments. Results: The rs53576 AG genotype was significantly associated with a lower risk of ASD (OR = 0.707, 95% CI: 0.512-0.975). A single genotype (AG) provided by the rs2254298 marker was found to be significantly associated with higher social communication scores (Parameter estimate = 1.833, SE = 0.762, p = 0.0171). This association was also seen in a Caucasian only and mothers as the respondent samples. No association was significant following false discovery rate adjustments. Conclusion: The findings from these studies provide limited support for the role of OXTR SNPs in ASD, especially in social communication skills. The clinical significance of these associations remains unknown, however, it is likely that these associations do not play a role in the severity of symptoms associated with ASD. Rather, they may be important in the appearance of social deficits due to the rs2254298 markers association with enlarged amygdalas. Description: Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2016-08-11 19:52:25.759 2016-08-15T04:00:00Z UPTAKE OF THE PERIODIC HEALTH EXAM AMONG ADULTS WITH INTELLECTUAL AND DEVELOPMENTAL DISABILITIES FROM 2003 TO 2015 http://hdl.handle.net/1974/14707 Title: UPTAKE OF THE PERIODIC HEALTH EXAM AMONG ADULTS WITH INTELLECTUAL AND DEVELOPMENTAL DISABILITIES FROM 2003 TO 2015 Authors: Smith, GLENYS Abstract: Background: Over the past decade, annual heath exams have been de-emphasized for the general population but emphasized for adults with intellectual and developmental disabilities (IDD). The purpose of this project was to determine if there has been an increase in the uptake of the health exam among adults with IDD in Ontario, to what extent, and the effect on the quality of preventive care provided. Methods: Using administrative health data, the proportion of adults (18-64 years old) with IDD who received a health exam (long appointment, general assessment, and "true" health exam), a high value on the primary care quality composite score (PCQS), and a health exam or high PCQS each year was compared to the proportion in a propensity score matched sample of the general population. Negative binomial and segmented negative binomial regression controlling for age and sex were used to determine the relative risk of having a health exam/high PCQS/health exam or PCQS over time. Results: Pre joinpoint, the long appointment and general assessment health exam definitions saw a decrease and the "true" health exam saw an increase in the likelihood of adults having a health exam. Post joinpoint, all health exam definitions saw a decrease in the likelihood of adults having a health exam. Pre joinpoint, all PCQS measures (high PCQS, long appointment or high PCQS, "true" health exam or high PCQS) saw an increase in the likelihood for adults to achieve a high PCQS or high PCQS/have a health exam. Post joinpoint, all PCQS measures saw a decrease in the likelihood for adults to achieve a high PCQS or high PCQS/have a health exam. Achieving a high PCQS was strongly associated with having a health exam regardless of health exam definition or IDD status. Conclusions: Despite the publication of guidelines, only a small proportion of adults with IDD are receiving health exams. This indicates that the publication of guidelines alone was not sufficient to change practice. More targeted measures, such as the implementation of an IDD-specific health exam fee code, should be considered to increase the uptake of the health exam among adults with IDD. Description: Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2016-08-08 18:54:05.415 2016-08-09T04:00:00Z An investigation of sugar-sweetened beverage consumption among Canadian youth http://hdl.handle.net/1974/14706 Title: An investigation of sugar-sweetened beverage consumption among Canadian youth Authors: Davis, Laura Abstract: Background: Consumption of sugar-sweetened beverages (SSBs) is an important public health problem in Canada, especially among adolescents. Estimates show that rates of SSB consumption are particularly high in the northern territories, especially in Nunavut. This is concerning given that regular SSB consumption is associated with obesity, diabetes and tooth decay, among other health concerns. Objectives: This thesis has two objectives. The first is to describe SSB consumption patterns among adolescents from Nunavut specifically, all three territories combined and the provinces.The second is to determine the association between individual and cumulative school food programs and SSB consumption. Methods: Data were obtained from the Health Behaviour in School-aged Children study (HBSC); a cross-sectional survey of Canadian youth in grades 6-10. All frequencies for food and beverage consumption were obtained from a 7-day food frequency questionnaire. SSB consumption consisted of a composite measure including soft drinks, sports drinks and energy drinks. The types of school food programs were obtained from an administrative questionnaire filled out by each school's Principal or delegate. Multilevel multivariate Poisson regression models were used to examine the associations between school food programs and SSB consumption. Results: Youth from Nunavut consumed the most SSBs (53.1% in 2010 and 55.0% in 2014 were daily consumers), followed by youth from the territories (31.1% in 2010 and 27.0% in 2014), then youth from the provinces (24.3% in 2010 and 19.1% in 2014). No significant relationships were found between school food programs and daily SSB consumption. Two school food programs were weakly associated with weekly SSB consumption: nutrition month activities (RR=0.93,CI=0.89, 0.98) and healthy options in the snack bar (RR=1.07, CI=1.01, 1.14). Conclusions:Rates of SSB consumption were highest among Nunavummiut youth followed by youth from all three territories combined and then the provinces. Little association was found between school food programs and SSB consumption among Canadian youth in grades 6-10. These findings point to the need for examining other determinants and potential areas for intervention, for reducing SSB consumption among Canadian youth, particularly in high consumer sub-populations. Description: Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2016-08-08 16:01:46.322 2016-08-09T04:00:00Z Adiposity, Sex Hormones, and Repetitive Element DNA Methylation in Healthy Postmenopausal Women http://hdl.handle.net/1974/14704 Title: Adiposity, Sex Hormones, and Repetitive Element DNA Methylation in Healthy Postmenopausal Women Authors: Boyne, Devon Abstract: INTRODUCTION: Low levels of methylation within repetitive DNA elements, such as long interspersed nuclear element-1 (LINE-1) and Alu repeats, are believed to epigenetically predispose an individual to cancer and other diseases. The extent to which lifestyle factors affect the degree of DNA methylation within these genomic regions has yet to be fully understood. Adiposity and sex hormones are established risk factors for certain types of cancer and other illnesses, particularly amongst postmenopausal women. The aim of the current investigation is to assess the impact of adiposity and sex hormones on LINE-1 and Alu methylation in healthy postmenopausal women. METHODS: A cross-sectional study was conducted using baseline data from an ancillary study of the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial. Current adiposity was measured using a dual-energy x-ray absorptiometry (DXA) scan, computed tomography (CT) scan, and balance beam scale. Historical weights were self-reported in a questionnaire. Current endogenous sex hormone concentrations were measured in fasting blood serum. Estimated lifetime number of menstrual cycles was used as a proxy for cumulative exposure to ovarian sex hormones. Repetitive element methylation was quantified in white blood cells using a pyrosequencing assay. Linear regression was used to model the relations of interest while adjusting for important confounders. RESULTS: Adiposity and serum estrogen concentrations were positively related to LINE-1 methylation but were not associated with Alu methylation. Cumulative ovarian sex hormone exposure had a "U-shaped" relation with LINE-1 regardless of folate intake and a negative relation with Alu methylation amongst low folate consumers. Androgens were not associated with repetitive element DNA methylation in this population. CONCLUSION: Adiposity and estrogens appear to play a role in maintaining high levels of repetitive element DNA methylation in healthy postmenopausal women. LINE-1 methylation may be a mechanism whereby estrogen exposure protects against cardiovascular and neurodegenerative illnesses. These results add to the growing body of literature showing how the epigenome is shaped by our lifestyle choices. Future prospective studies assessing the relation between levels of repetitive element DNA methylation in healthy individuals and subsequent disease risk are needed to better understand the clinical significance of these results. Description: Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2016-08-08 12:12:30.315 2016-08-09T04:00:00Z


text:
Gateway NV55S07u-6344G50Mnrk
SpecificationsNotebook: Gateway NV55S07u-6344G50Mnrk (NV Series)
Processor: AMD A-Series A6-3400M
Graphics Adapter: AMD Radeon HD 6520G
Display: 15.6 inch, 16:9, 1366x768 pixels, glossy: yes
Weight: 2.6kg
Price: 500 euro
Sold in: Anglo-America
Average of 1 scores (from 1 reviews)
Reviews for the Gateway NV55S07u-6344G50Mnrk
Source: Comp Reviews
Gateway's aging NV platform is certainly starting to feel like updating. The NV55S07u-6344G50Mnrk does offer a quad core AMD processor which gives it better than expected graphics and the numeric keypad is something that many 15-inch laptops are dropping these days. The problem is that is the battery life is below much of the Intel based laptops in this price range and it lacks a USB 3.0 port which some of the Gateway NV series has included in the past.
Single Review, online available, Short, Date: 10/19/2012
Rating: Total score: 60%
AMD Radeon HD 6520G:
Integrated processor graphics card (in the A6-Series of Llano APUs) without dedicated graphics memory and only 320 of the 400 shader cores.
Non demanding games should be playable with these graphics cards.
» Further information can be found in our Comparison of Mobile Graphics Cards and the corresponding Benchmark List.
A6-3400M: Llano quad-core APU clocked at 1.4-2.3 GHz (Turbo Core) featuring an integrated Radeon 6520G (320 cores, 400MHz) graphics card.» Further information can be found in our Comparison of Mobile Processsors.
15-16 inch is a standard display size for laptops and offers the biggest variety of products.» To find out how fine a display is, see our DPI List.
2.6 kg:
This weight is representative for typical laptops with a 14-16 inch display-diagonal.
Gateway: Gateway, Incorporated. is a computer hardware company based in California which develops, manufactures, supports, and markets a wide range of personal computers, computer monitors, servers, and computer accessories. AOL acquired Gateway.net, the online component of Gateway Inc., in 1999. 2007, Acer completed its acquisition of Gateway for approximately US$710 million. The market share outside of the US market is rather low.
60%: Such a bad rating is rare. There exist hardly any notebooks, which are rated worse.
» Further information can be found in our Notebook Purchase Guide.


text:
Change Location
ACE Fit Share
Fit Life Articles
Summer has arrived! Here is a leg workout that will have you feeling strong, agile and amazing in your favorite shorts, skirt or swim suit.
"You need a sports drink after you work out to help your body recover." Sound familiar? The world of exercise is cluttered with myths and misperceptions. Many of these myths persist because of the way fitness is portrayed in the media; other myths withstand the test of time...
Change means pushing ourselves beyond our comfort zone and entering into unfamiliar territory. Let's explore five tools for breaking a major life change down into smaller, more manageable, parts.


text:
- Report: #431635
Report - Rebuttal - Arbitrate
Complaint Review: OAN Services
OAN Serviceshttp://www.billview.com/oan/faq.htm Internet U.S.A.
OAN Services - Billview - Billing Concepts On my Verizon Bill--Could not even tell me who they were billing for Internet
*Consumer Comment: i had this charge mine was premium msg
*Consumer Comment: Same thing is happening to me!!
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A business' first
line of defense
on the Internet.
If your business is
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Click here now..
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Fix it the right way.
Corporate Advocacy Program™
It has shown up again this month, but with a description, for a "residential E-mail fee". I don't know what this is and will be calling them again. And from the number of complaints I am seeing here and on other sites about this organization, it appears they have gone from using the phone to manipulate things to using the internet and, apparently according to the representative I talked to, website popups, a very manipulative way of tacking charges on unsuspecting persons' bills.
Does anyone know what a "residential e-mail" is?? I pay my DSL company for my email and the only other one is a Yahoo (free e-mail).
Berlin, Massachusetts
This report was posted on Ripoff Report on 03/06/2009 08:11 PM and is a permanent record located here: http://www.ripoffreport.com/r/OAN-Services/internet/OAN-Services-Billview-Billing-Concepts-On-my-Verizon-Bill-Could-not-even-tell-me-who-431635. The posting time indicated is Arizona local time. Arizona does not observe daylight savings so the post time may be Mountain or Pacific depending on the time of year.
Ripoff Report has an exclusive license to this report. It may not be copied without the written permission of Ripoff Report.
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- Only search one name at a time if Company has many AKA's.
#1 Consumer Comment
i had this charge mine was premium msg
AUTHOR: Carol - (U.S.A.)
SUBMITTED: Wednesday, March 25, 2009POSTED: Wednesday, March 25, 2009
Are you an owner, employee or ex-employee with either negative or positive information about the company or individual, or can you provide "insider information" on this company?
#2 Consumer Comment
Same thing is happening to me!!
AUTHOR: Uiucstudent - (U.S.A.)
SUBMITTED: Sunday, March 15, 2009POSTED: Sunday, March 15, 2009
Are you an owner, employee or ex-employee with either negative or positive information about the company or individual, or can you provide "insider information" on this company?
Advertisers above have met our
strict standards for business conduct.


text:
After upgrading to WP2.1 to my shock and horror, all my link categories had been converted to empty post categories. After my initial shock, I decided to conform to the new blogroll system and assigned all links to regular categories and deleted all the emty converted ones... Sadly, the system doesn't allow me to delete that last (default) link category. Now I have two default categories in my category list. Hope that will not create problems later on... Anyway, here's my remaining problem:
I cannot seem to get wp_list_bookmarks() to return a < li >< / li > item list without any category headings or wrapping < ul >...< / ul > around it
Tried about every combination of the related arguments I can find on http://codex.wordpress.org/Template_Tags/wp_list_bookmarks
This comes closest:
but STILL there is a wrapping <li id="linkuncat" class="linkcat">< ul >...< /ul >
Oh, and what about the option 'show_description'? That doesn't seem to work at all! :(
Anybody in a hurry to release 2.1 ?!?
If anyone can point me to the right arguments, I'll be happy to change the documentation...


text:
- Report: #251743
Report - Rebuttal - Arbitrate
Complaint Review: Freedom Ring
Freedom RingPark Blvd. Seminole, Florida U.S.A.
Freedom Ring Scam Artist Comp., Fraudulent Billing, Idenity Theft, Theif, Seminole Florida
Ripoff Report
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willing to make a
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customer satisfaction
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Fix it the right way.
Corporate Advocacy Program™
I am a 19 year old man with a full time job, a wife, and a son, that works my butt off for everything I have.
Theese lazy, cowardess, leeches to society are flat out robbing me over the Internet I suspect. If anyone has any information regarding my situation please send a message to me through this report.
Eastern North Carolina, North Carolina
This report was posted on Ripoff Report on 06/01/2007 05:15 PM and is a permanent record located here: http://www.ripoffreport.com/r/Freedom-Ring/Seminole-Florida/Freedom-Ring-Scam-Artist-Comp-Fraudulent-Billing-Idenity-Theft-Theif-Seminole-Florida-251743. The posting time indicated is Arizona local time. Arizona does not observe daylight savings so the post time may be Mountain or Pacific depending on the time of year.
Ripoff Report has an exclusive license to this report. It may not be copied without the written permission of Ripoff Report.
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In order to assure the best results in your search:
- Keep the name short & simple, and try different variations of the name.
- Do not include ".com", "S", "Inc.", "Corp", or "LLC" at the end of the Company name.
- Use only the first/main part of a name to get best results.
- Only search one name at a time if Company has many AKA's.
Advertisers above have met our
strict standards for business conduct.


text:
Madoff Trustee Seeks to Block Merkin Deal With N.Y.
The trustee liquidating Bernard Madoff's former firm asked a federal appeals court to block a $410 million settlement between the state of New York and money manager J. Ezra Merkin.
New York Attorney General Eric Schneiderman announced the settlement with Merkin, who controlled four funds that fed more than $2.4 billion of investor money into Madoff's fraud, in June 2012. Trustee Irving Picard tried to block the deal, claiming it would hamper his efforts to collect assets for Madoff investors.
In arguments before the appeals court in Manhattan today, David Sheehan, a lawyer for Picard, asked a three-judge panel to reverse lower court decisions permitting the settlement to go forward.
Andrew Cuomo, New York's former attorney general and now the state's governor, sued Merkin in 2009 claiming Merkin and his Gabriel Capital Corp. defrauded investors, including charities and educational institutions, by turning their money over to Madoff without disclosing the con man's role.
Madoff is serving a 150-year sentence after pleading guilty to a fraud that wiped out $17 billion of customers' principal.
The case is Picard v. Schneiderman, 13-01785, Second U.S. Circuit Court of Appeals (Manhattan).


text:
By Staff Sgt. Jason Douglas, 2nd Brigade Combat Team, 1st Cavalry Division Public AffairsJune 23, 2009
FORWARD OPERATING BASE WARRIOR, KIRKUK, Iraq - As part of the Security Agreement signed between the United States and Iraq on January 1, 2009, all operations conducted within Iraq must be led by Iraqi Security Forces with US forces in support. That includes regular security patrols, which serve to support stability in a village or town and also serves to strengthen the bond between Iraqi Security and Coalition Forces.
Soldiers from 1st Battalion, 8th Cavalry Regiment, 2nd Brigade Combat Team, 1st Cavalry teamed up with Iraqi soldiers from the 1st Battalion, 47th Iraqi Army Brigade and made the drive to Gumbaltar for the patrol June 8.
According to 2nd Lt. Christopher Freeman, Sheburne, Vt. native, and fire support officer with 1st Bn., 8th Cav Regt., the purpose behind the patrol was more than just to show partnership between the IA and Coalition forces.
"We meet and greet the residents of Gumbaltar to find out how we can help," Freeman said. "But, it is also an opportunity to observe the IA function."
Soldiers from 3rd platoon, 1st Bn., 8th Cav. Regt. have been working with the 1st Bn., 47th IA Brigade since 2nd BCT arrived in Kirkuk and, according to Freeman, part of that partnership has been training the IA to function on its own.
"The relationship between us [Coalition forces] and the IA has come around and gotten better," Freeman said. "By going on these patrols we can find out how to support each other with better training."
Freeman said his unit has been involved in training the IA on conducting vehicle searches, clearing buildings, and setting up traffic control points, with the goal of helping the IA perform these tasks on their own.
"We want them to be successful in order to protect their fellow Iraqis," Freeman explained. "They [the IA] have indicated they truly care about their population and show that by better coordinating security with the Iraqi Police and recognizing the benefits of our training."
It was the first combined patrol for Lt. Mehvan Islam Hussein, a personnel officer with the 1st Bn., 47th IA, who was optimistic about the partnership.
"This is my first time on patrol with U.S. forces, but I feel it is very useful in building our confidence and hope it continues," Mehvan said. "It also helps by showing the population that the Iraqi Army is here to help them."
Mehvan also stated that the benefits of training with U.S. forces will help them fulfill these duties once U.S. forces are gone.
The village [Gumbaltar] is primarily Turcoman and many of the soldiers in the 1st Bn., 47th IA who operate in this area are Arab, this will build their trust in them, Mehvan said.
According to Freeman, the combined patrols and training with the IA will continue, and already he has recognized an increase in their abilities.
"They [IA] are well on their way to functioning on their own," Freeman said.


text:
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Start Developing Effective Strategies for Chronic Illness with Steven Hornewith Steven Horne
In this three-part webinar, Steven Horne is going to teach you how to work with a person to identify root causes and develop effective natural healing strategies for that person, using ten chronic health problems as examples. The webinars will be held on Wednesdays, September 7, 28, October 5 at 6:00 Mountain Time. The price includes the book, Modern Herbal Medicine (a $32.95 value), which will be used as a reference throughout the class.
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The pharmaceutical industry doesn't focus on getting people well from chronic diseases. Instead, it focuses on treating symptoms, because it is more profitable to simply relieve symptoms than it is to restore a person to health. In natural healing, we don't want to treat symptoms. We want to help a person recover their health.
This requires us to think beyond the disease symptoms that the person is concerned about. We have to look deeper and figure out the root cause of people's problems, so we can develop a strategy that will get them well. This strategy is going to be different for each individual, even if they have the same disease.
This webinar will discuss how to look beyond the disease and understand it's causes. Once you understand the cause of the person's ill health, it is easy to formulate a strategy that will help them actually heal. You can do this even with people who have diseases that you've never heard of before. In other words, understanding Western medical diagnosis isn't necessary to get effective results with natural healing.
In this three-part webinar, Steven Horne is going to show you how to work with a person to identify root causes and develop effective natural healing strategies for that person, using ten chronic health problems as examples. Here is what you'll learn in each of the sessions:
In session one you'll learn why developing a healing strategy is so important and how to formulate one. We'll cover three problems related to the respiratory and immune systems: allergies, autoimmune disorders, asthma and COPD.
In session two you'll learn about four important health issues related to the nervous system: anxiety, depression, stress and headaches, including migraines.
In session three you'll learn about three more chronic health problems: arthritis, hypertension and low thyroid. We'll also summarize what we've learn and discuss how you apply this information to diseases you've never heard of and you can't find in any natural healing books.
The webinars will be held on Wednesdays, September 7, 28, October 5 at 6:00 Mountain Time. They will be recorded, so you don't have to be able to attend the live webinars to participate in the class. The price includes the book, Modern Herbal Medicine (a $32.95 value), which will be used as a reference throughout the class. Cost for the course is $59).
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The liver is the primary organ responsible for breaking down toxins that get into our body and turning them into water soluble compounds that can be eliminated from the body. Problems with liver detoxification can cause environmental illness and the "healing crisis" talked about in natural medicine. In this article, I explain the basic process of liver detoxification and how supplements can improve liver detoxification.
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Everyone experiences pain at various times, but if we want to get rid of pain permanently, instead of just masking it with pain-killing drugs, then we need to understand what our pain is telling us. We need to identify the underlying cause of our pain and remove it, rather than numbing it. Fortunately, nature has many tools to help us do this. Learn how natural remedies can ease our suffering in this article.
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The human immune system is a marvel. Most of the time it does a wonderful job of protecting us from infections, toxins and abnormal cells of all kinds. When the immune system becomes confused it can start tagging the body's own tissues and proteins as if they were foreign invaders. This causes the immune system to attack and damage the body's own tissues. Medicine has dubbed the diseases where this happens as autoimmune disorders. This article talks about the probable causes and basic approach to natural therapy for these conditions.
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Introducing Block Therapy and Fluid Isometrics
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- April 18, 2016
- Complete Listing of Free Webinars
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This is a free webinar about Deana Hansen's techniques for resculpting your body, reducing pain and improving your health. If you have weight problems, suffer from pain in the back, neck or other body parts and would like to look and feel younger, this webinar has some important information that can help you to achieve these goals.
Featured Courses and Programs
Effective Healing Strategies for Chronic Illness
- Product
- July 21, 2016
- Complete Listing of Paid Webinars, Recorded Webinars, Upcoming Classes
You can practice "cookbook" alternative healing, which is to simply mimic the medical approach, substituting natural remedies for drugs to try to treat the disease, or you can use a genuinely holistic approach, which means looking beyond the disease to understand why the person is sick. When you do this the strategy for healing is based on the person, not the disease. This class will help you learn how to do this.
An Introduction to Field Botany
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- March 30, 2016
- Advanced Training Courses, Family Herbalist Certification (FHC)
In this class you'll learn skills of basic plant identification and how to recognize and use numerous plants in all the major botanical families. You'll not only receive about 90-120 minutes of webinar instruction in each class, you'll also have access to online quizzes and learning activities to help you master the material. Plus, I'll keep adding new materials and resources to the course, which you can access as they become available.
Practical Iridology Manual
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- February 22, 2016
- Books and Materials
In the past, the Practical Iridology manual has only been available as part of our Practical Iridology (IIPA Level One) class. You can know purchase it separately for self study of this amazing health assessment tool.
Traditional Health Assessment
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- January 1, 2016
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In Traditional Health Assessment you'll learn the process of assessing the various aspects of a person's health, starting with their constitution, the root causes of illness in their life, their biological terrain, and their body systems that are weak. It provides you with the tools you need to analyze all the aspects of a person's health.
Running a Consulting Business
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- January 1, 2016
- Certified Emotional Healing Coach (CEHC), Certified Herbal Consultant (CHC), Certified Iridologist


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Top Definition
Someone who deserves a b& for the good of the community. Usually a fag and loser hated by everyone. Coined in Feb of 2009 for a random poser who sucks at Warcraft. The term is now being used across the internets.
Banwell now
by 231h0xi3 March 08, 2009
Trending Now
Can you define these popular missing words?


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Connect With Us
Meet Our Conductors
Stefan Sanderling
Principal Conductor
"World Class Concert"- Volksblatt - May 2012
Awarded the Kilenyi Medal of Honor (Bruckner Medal) by the Board of Directors of the Bruckner Society of America for his contribution to the works of Bruckner in April 2012, Stefan Sanderling is a leading international conductor of his generation. He has held the position of Principal Conductor and Artistic Advisor of the Toledo Symphony Orchestra since 2003, a post which led to his hugely successful debut at Carnegie Hall as part of the "Spring for Music" series conducting Previn's "Every Good Boy Deserves Favour" and the powerful Shostakovich Symphony No. 6. Mr. Sanderling also holds the position of Conductor Emeritus and Artistic Advisor of the Florida Orchestra.
In 1989, Sanderling became one of Germany's youngest conductors to take the position of Chief Conductor at the Brandenburgische Philharmonie and the Potsdam Opera. After five years, he went on to become Music Director of the Philharmonic Orchestra and Staatstheater in Mainz until 2001. He also served as Music Director of the Orchestre de Bretagne in France, before leaving to take up his post as Music Director of The Florida Orchestra a position he held until 2012. He has also held the position of Music Director of the Chautauqua Symphony Orchestra 2006/2011.
Born in East Berlin in 1964, the son of the late legendary conductor Kurt Sanderling, Mr. Sanderling studied musicology at the University of Halle and conducting at the conservatory in Leipzig with Kurt Masur before leaving East Germany to continue his studies in Los Angeles at the University of Southern California.
Mr. Sanderling made his U.S. debut at the Tanglewood Music Festival. Since then he has led such prestigious North American Orchestras as the Baltimore Symphony, Colorado Symphony, Detroit Symphony, Houston Symphony, Indianapolis Symphony, Los Angeles Philharmonic, Montreal Symphony, Ottawa Symphony, Saint Louis Symphony, Salt Lake City Symphony, San Francisco Symphony, Toronto Symphony, Vancouver Symphony, and the Saint Paul Chamber Orchestra, to name a few.
Worldwide guest conducting appearances include the Bamberg Symphony, Berliner Sinfonie Orchester, Berliner Staatskapelle, Bournemouth Symphony, Liechtenstein Symphony Orchestra, London Philharmonic, London Symphony, Mozarteum Orchestra (Salzburg), NDR Symphony Orchestra Hamburg, NTO (Vienna), Philharmonia Orchestra London, Prague Symphony, Rotterdam Philharmonic, Royal Philharmonic London, Scottish Chamber Orchestra, St. Petersburg Philharmonic, Staatskapelle Dresden, and the Vienna Radio Symphony. Mr. Sanderling has also guest conducted at both the Deutsche Oper and Komische Oper in Berlin. He made debuts in Australia with the Sydney Symphony Orchestra and in Japan with the Yomiuri Nippon Symphony Orchestra. His highly successful debut with the NHK Symphony of Tokyo has resulted in regular appearances with that orchestra and several other orchestras in Tokyo and throughout Japan.
Also an active recording artist, Stefan Sanderling made his first recording on the Sony Classics label with the London Symphony Orchestra. Quickly followed by three CDs with the Royal Philharmonic Orchestra featuring symphonies by Haydn and Mendelssohn. For Naxos, he has recorded the complete Tchaikovsky Orchestral Suites with the RTE National Orchestra of Ireland and Stravinsky's ballet "Pulcinella" with the Bournemouth Symphony Orchestra. During his time as Music Director of the Orchestre de Bretagne he recorded/released 14 CD's in all, some featuring early French music. In early 2012 he recorded works by Frederick Delius with the Florida Orchestra which will be released later this year.
For further information please contact:
Mark Z Alpert at Columbia Artists Management LLC
(212) 841 9568
© 2013/14 Please discard all previous biographies.
Sara jobin
interim resident CONDUCTOR
Grammy-nominated conductor Sara Jobin has a passion for opera, American and new music. As Chief Conductor of the Center for Contemporary Opera in New York since 2011, she premiered and recorded Michael Dellaira's The Secret Agent in New York, followed by repeat performances at the Armel Festival in Szeged, Hungary and Avignon, France. In addition to an upcoming Eugene Onegin with Opera Idaho, credits include Ein Deutsches Requiem with Albany Pro Musica; subscription concerts with both the Toledo Symphony and Opera; Madama Butterfly with Opera Santa Barbara; Il Matrimonio Segreto with Pittsburgh Opera; Der fliegende Holländer with Arizona Opera, stepping in for three performances with no rehearsal; Susannah, The Ballad of Baby Doe, and Our Town with Opera Idaho where Jobin is Music Director of the Made in America Series; Carmen and the Suite from Ricky Ian Gordon's The Grapes of Wrath with Anchorage Opera; and the world premiere of Philip Glass' The Bacchae with the New York Shakespeare Festival. She has also conducted Symphony Silicon Valley, the Dayton Philharmonic, the Bochumer Symphoniker in Germany, The Orchestra of St. Luke's, and The Little Orchestra Society in New York.
At age 16, Jobin attended Harvard and Radcliffe Colleges, where she was a Leonard Bernstein Music Scholar and won the John Knowles Paine Traveling Fellowship. She studied conducting with Charles Bruck at the Pierre Monteux School in Maine. In 2004, she had the honor of making history as the first woman to conduct mainstage subscription performances at the San Francisco Opera.
Not one to fit neatly into categories, Jobin has a black belt in judo, and was the 1998 and 2006 national champion in Ju-no-kata, which she studied with legendary teacher Shihan Keiko Fukuda, who was the highest ranking woman in the history of the sport. She sang in the gospel choir in The Pursuit of Happiness featuring Will Smith, prefers to ride a bicycle for transportation year-round, loves organic farming, and is looking for more opportunities to conduct sacred music.


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tag:blogger.com,1999:blog-384329692727378622.post1110493957938477380..comments2016-08-27T10:58:48.307-04:00Comments on On Second Scoop: Ice Cream Reviews: Rocky Road Klondike Bar ReviewDubba firstname.lastname@example.com:blogger.com,1999:blog-384329692727378622.post-51903907113796196862014-06-26T05:24:28.506-04:002014-06-26T05:24:28.506-04:00Living in the UK, where I've eaten these I hav...Living in the UK, where I've eaten these I have no idea ...

Besides Klondike as a young child I've also tried Drumstick: Bazooka ... Cap'n'Crunch peanut butter (chocolate bar) ... Kool Aid (Tropical Punch, Strawberry etc.) ... Jelly Belly ... Hershey's peanut butter (fairy cakes) ... Hershey's Brownie Cookies ... young then, but were put up in a Hospice around that time...

Reading Maximum Carnage (Marvel Comics) and then playing the SEGA Genesis game and reading the X-Men Anniversary edition cover by Joe Madureira(Uncanny X-Men)and having a signed copy of X-Men by Marc Silvestri signed at a "comic convention," that relatives had taken me to.

Hey brought back, memories ... take a look "guys,": http://email@example.com:blogger.com,1999:blog-384329692727378622.post-13758429764293049592011-05-12T08:14:01.376-04:002011-05-12T08:14:01.376-04:00Ah shame you didnt really enjoy these :( nothing w...Ah shame you didnt really enjoy these :( nothing worse i think when you eat something and feel completely let down afterwards.Lot-O-Chochttp://email@example.com:blogger.com,1999:blog-384329692727378622.post-12789318545587487712011-05-11T15:31:24.077-04:002011-05-11T15:31:24.077-04:00I did give it a try earlier and I like it but name...I did give it a try earlier and I like it but name is very misleading. If it was called like chocolate covered marshmallow or something among those lines I think I'd be less disappointed since it doesn't live up to it's name at all. Mine had a nice crunch though and at times did taste just like a marshmallow that was just dipped into chocolate fudge. As a treat by itself I liked it but it's name makes it a firstname.lastname@example.com:blogger.com,1999:blog-384329692727378622.post-35821549799157884622011-05-11T06:47:48.793-04:002011-05-11T06:47:48.793-04:00The more I think about these, the more disappointe...The more I think about these, the more disappointed I become, and that doesn't happen to often. I'm thinking it's because of the Rocky Road name.

@Nick: definitely let us know what you think.Dubbahttp://firstname.lastname@example.com:blogger.com,1999:blog-384329692727378622.post-85309223928610113722011-05-10T20:11:49.052-04:002011-05-10T20:11:49.052-04:00I tried these on Saturday night and was also super...I tried these on Saturday night and was also super disappointed :( I liked the marshmallow ice cream but that was about it...I was hoping you'd review email@example.com:blogger.com,1999:blog-384329692727378622.post-72995865527081555362011-05-10T17:03:04.749-04:002011-05-10T17:03:04.749-04:00This is disappointing to hear. I've had a box ...This is disappointing to hear. I've had a box of these in my freezeer for awhile now but I just never got around to having one yet. I think I'll try one soon to see if they're as big of a fail as you say. Great review like always email@example.com


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Search-And-Destroy Show Seeks Bad Art [AUDIO]
An art gallery in Casper is putting out a call for bad art.
An art gallery in Casper is putting out a call for bad art.
Not only was last week's East Coast earthquake nice enough not to seriously injure anybody, but its rumbling effects may have actually helped a deaf man hear again.
Polygamous sect leader Warren Jeffs is in critical condition after being rushed to a Texas hospital on Tuesday, a prison official said. The 55-year-old convicted child rapist grew so weakened by fasting that he had to be removed from his solitary prison cell for medical treatment.
Fairy mania is sweeping a neighborhood in Guadalajara, Mexico after a local man claimed he captured one of the mythical sprites.
Here's a look at some interesting events that took place on this day in history:
1812 – The American frigate USS Constitution earns the nickname "Old Ironsides" after defeating the British frigate HMS Guerriere off the coast of Nova Scotia, Canada (More info)
1909 – The first race is held at the Indianapolis Motor Speedway, the home of the Indianapolis 500 (More info)
In June, the Food and Drug Administration released nine new warning labels that depict in graphic detail the negative health effects of tobacco use. Now, four of the five largest US tobacco companies want a judge to stop the government from using them.
Several months ago, aerial photos taken of a previously-unknown tribe in the Amazon rainforest captured imaginations and got a lot of people talking.
The tribe has since vanished, and now Brazilian authorities are worried cocaine smugglers are responsible for its disappearance.
When photographs of U.S. soldiers abusing suspected Iraqi insurgents were released to the public in 2004, they caused an international outcry.
Over the weekend, the man who orchestrated the abuses at Abu Ghraib was released from prison.
According to a multi-national survey of over 9,000 adults by the World Health Organization, France and the United States are the two most mentally depressed countries in the world.
Twenty-one percent of French citizens have had a major depressive episode, followed by the United States, at 19.2 percent. Belgium, New Zealand and The Netherlands are also among world's most depressed nations, by this metric.


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First, a bit of good news. Today I learned that my essay, "Black Confederates Out of the Attic and Into the Mainstream" has been accepted for publication in The Journal of the Civil War Era. I suspect I will have to wait some time before I see it in print. I argue that as historians and teachers we need to be thinking harder about how the Internet has changed not only how history is written, but more importantly, how it is being consumed and shared. From the essay:
The success of the black Confederate phenomena can be traced directly to the expansion of the Internet, including access to rich databases of primary sources and the availability of digital tools such as blogs, wikis, and other platforms that allow practically anyone the opportunity to publish a website and engage and influence a wide readership. This has led to a sharp increase in the amount of history published online by individuals and organizations with little or no formal training in the field. As a result, the democratization of history through online publishing continues to blur the distinction between professional and popular historians and challenges any presumption of who has the right to research and publish history. While professional historians assume the responsibility of critically assessing the work of their peers they have yet to explore their role in responding to and evaluating online content. The black Confederate narrative provides academic and public historians with an opportunity to reflect on how they might engage history enthusiasts and the broader general public in an environment that promotes an unregulated marketplace of ideas.
Next week I am heading to Gettysburg College to take part in this year's Civil War Institute. It's always a blast and this year is extra special given that is the 150th anniversary of the battle. I hope to be able to soak up some of the sesquicentennial vibe without having to be there in the middle of all that craziness the following week. This year I am going to be working with a group of high school students, who will be taking part in the conference. It's nice to have a chance to be filmed for C-SPAN, but I much prefer a classroom setting where I can interact with students.
I am going to use the opportunity to introduce students to the subject of Civil War memory by having them compare Lincoln's Gettysburg Address with Woodrow Wilson's 1914 address from the 50th anniversary. The text is below, but as you read it think about how you would introduce this speech to a group of students.
- What questions would you ask to frame the two documents?
- What sentences, phrases, or words stand out to you and why?
- What was Wilson's goal in addressing his audience in 1914?
- What events would you reference to frame the historical context of this speech?
Thanks in advance for sharing your thoughts. [click to continue…]


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Definition from Wiktionary, the free dictionary
- (roofing) A moderate deformation or buckling of sheet material, particularly common with flat sheet metal surfaces. Typically caused by uneven stresses at the fastening points. This terminology also refers to the popping sound made when pressure is applied to the deformed sheet forcing the deformation in the opposite direction.
- (manufacturing) The movement of a perceived flat surface across its intended plane due to the application of a shear force. Caused by unequal stretching of the material inside the surface of the panel while retaining the perimeter. This term refers to the technique used to operate an oil can or an "oiler" whereas the user inverts the oiler and holds it between the index and middle finger while applying pressure to the bottom with their thumb to ultimately pump oil out of the spout. This phenomenon has additional exposure in the home canning environment where during the cooling process the lid of the jar has negative atmospheric pressure sufficient to pull or "pop" the lid center down assuring the lid has sealed to the jar. Membrane buttons on electronic devices give this sensation as well.


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UWM's proposed water school
Restaurant is best use
I read with interest the two views of what should happen with the space Pieces of Eight currently has on the lakefront in the May 31 Crossroads (Milwaukee County Supervisor Gerry Broderick's "Forethought, execution are the essentials" and Milwaukee Ald. Michael Murphy's "City must not miss golden opportunity"). One view was not expressed.
As a former employee of Pieces of Eight (in the 1970s) and a customer since then, I enjoyed the beautiful facility on the lakefront. With my disabilities, I walk or ride along the lakefront. I can't use the beaches, but I certainly enjoyed a good meal with a beautiful view. One writer referred to Pieces of Eight as forgettable. Maybe for him, but I have had some terrific meals there. Too bad management slipped as far as it did in recent years.
Putting a school there would cost the taxpayers money since it is a state school. While the city could get rent, it would have to increase the current rent, since it will no longer collect property taxes.
When Pieces of Eight wanted to add a second level, the city said no; it would block the view. Why can the school build a second level? If the parking lot becomes a grass lot, where will the students park? A select few people will be able to use the facility. Put in a more successful restaurant operator, and everyone can enjoy.
Bruce Lemke
West Milwaukee
Look at other venues
I really enjoyed both Gerry Broderick's and Michael Murphy's op-eds regarding the pros and cons of having University of Wisconsin-Milwaukee's School of Freshwater Sciences at the former Pieces of Eight restaurant location.
While I do agree that Milwaukee as a whole will benefit from such a school, I do not agree that locating it at the former Pieces of Eight site is beneficial to our tourism industry. This tract of land, surrounded by Discovery World, Summerfest and the Calatrava, needs something to bring people down to the lakefront, and a state-of-the-art academic facility is not the answer. Nor do I believe there is a need to move the Transit Center elsewhere. There is nothing wrong with its current location across the street.
How about a restaurant that highlights some of the assets we have here in the great state of Wisconsin? Pictures of Packers, Badgers, Bucks and Brewers will fill the walls while down-home, kid friendly food (with cheese, of course) adorns the menu.
Yes, a state-of-the-art facility for freshwater sciences is in order; we all agree. However, there are plenty of other venues for this facility that would fill the bill.
Let's not forget that tourism dollars help our economy, and since we have several other attractions in that location, let's expand upon what is already there instead of trying to stick an academic building in the middle of it all.
Mary Bivens
New Berlin
Before making a decision, we need a few answers
I've been following news about the University of Wisconsin-Milwaukee's proposed School of Freshwater Sciences in our great city ever since I heard Richard Meeusen from Badger Meter talk about it at the Renewable Energy Conference earlier this year. So I read the views of Gerry Broderick and Michael Murphy in the May 31 Crossroads with great interest.
I've always assumed that locating this school and facility on the lakefront was a scientific necessity. Broderick seems to think it's not. Can we get a clear disposition on this? Also, does our "golden opportunity" to remain a United Nations Global Compact City require that the facility be located on the lake? This is not clear from Murphy's piece. We need answers in order to resolve this issue.
Annette Gelhar
Building should interact with its surroundings
Architect Frank Lloyd Wright argued that well-designed buildings are of the land and not on the land. If so, then the University of Wisconsin-Milwaukee's School of Freshwater Sciences for Pier Wisconsin should be of the water and not on the water; of the pier and not on the pier.
I suggest that the upper floor of UWM's planned two-story building be constructed at pier level. The lower level would be built into the pier and partially submerged in Lake Michigan. This lower level would feature underwater observation windows reminding academicians and visitors of the very water the school's research is seeking to understand and protect.
Such a design would constitute a dramatic architectural statement, yet reduce the school's visual impact on the lakefront, where a sensitive aesthetic toward institutional neighbors ought to be a high priority.
The Calatrava wing of the Milwaukee Art Museum reaches into the sky. Discovery World anchors the shore. The UWM School of Freshwater Sciences, sited in between, would best complement both by embracing Lake Michigan.
Explaining his concept of organic architecture, Wright argued that a building's form and function are one. Ideally, the new UWM school should be one with Lake Michigan, not simply tower over it.
Ron Legro
Whitefish Bay
Across the Board
The Journal Sentinel Editorial Board's blog on the day's happenings as they happen.


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Publications (25)
Article: Methyl-substitution of an iminohydantoin spiropiperidine β-secretase (BACE-1) inhibitor has a profound effect on its potency[Show abstract] [Hide abstract] ABSTRACT: The IC50 of a beta-secretase (BACE-1) lead compound was improved ∼200-fold from 11μM to 55nM through the addition of a single methyl group. Computational chemistry, small molecule NMR, and protein crystallography capabilities were used to compare the solution conformation of the ligand under varying pH conditions to its conformation when bound in the active site. Chemical modification then explored available binding pockets adjacent to the ligand. A strategically placed methyl group not only maintained the required pKa of the piperidine nitrogen and filled a small hydrophobic pocket, but more importantly, stabilized the conformation best suited for optimized binding to the receptor. Copyright © 2015 Elsevier Ltd. All rights reserved.
Article: Discovery of pyrrolidine-based β-secretase inhibitors: Lead advancement through conformational design for maintenance of ligand binding efficiency[Show abstract] [Hide abstract] ABSTRACT: We have developed a novel series of pyrrolidine derived BACE-1 inhibitors. The potency of the weak initial lead structure was enhanced using library-based SAR methods. The series was then further advanced by rational design while maintaining a minimal ligand binding efficiency threshold. Ultimately, the co-crystal structure was obtained revealing that these inhibitors interacted with the enzyme in a unique fashion. In all, the potency of the series was enhanced by 4 orders of magnitude from the HTS lead with concomitant increases in physical properties needed for series advancement. The progression of these developments in a systematic fashion is described.
- [Show abstract] [Hide abstract] ABSTRACT: This Letter describes the one pot synthesis of tertiary carbinamine 3 and related analogs of brain penetrant BACE-1 inhibitors via the alkylation of the Schiff base intermediate 2. The methodology developed for this study provided a convenient and rapid means to explore the P1 region of these types of inhibitors, where the P1 group is installed in the final step using a one-pot two-step protocol. Further SAR studies led to the identification of 10 which is twofold more potent in vitro as compared to the lead compound. This inhibitor was characterized in a cisterna magna ported rhesus monkey model, where significant lowering of CSF Abeta40 was observed.
Article: SAR of tertiary carbinamine derived BACE1 inhibitors: Role of aspartate ligand amine pKa in enzyme inhibition[Show abstract] [Hide abstract] ABSTRACT: The optimization of tertiary carbinamine derived inhibitors of BACE1 from its discovery as an unstable lead to low nanomolar cell active compounds is described. Five-membered heterocycles are reported as stable and potency enhancing linkers. In the course of this work, we have discovered a clear trend where the activity of inhibitors at a given assay pH is dependent on pK(a) of the amino group that interacts directly with the catalytic aspartates. The potency of compounds as inhibitors of Alphabeta production in a cell culture assay correlated much better with BACE1 enzyme potency measured at pH 7.5 than at pH 4.5.
- [Show abstract] [Hide abstract] ABSTRACT: During our ongoing efforts to develop a small molecule inhibitor targeting the beta-amyloid cleaving enzyme (BACE-1), we discovered a class of compounds bearing an aminoimidazole motif. Initial optimization led to potent compounds that have high Pgp efflux ratios. Crystal structure-aided design furnished conformationally constrained compounds that are both potent and have relatively low Pgp efflux ratios. Computational studies performed after these optimizations suggest that the introduction of the constraint enhances potency via additional hydrophobic interactions rather than conformational restriction.
Article: Discovery of aminoheterocycles as a novel β-secretase inhibitor class: pH dependence on binding activity part 1[Show abstract] [Hide abstract] ABSTRACT: We have developed a novel series of heteroaromatic BACE-1 inhibitors. These inhibitors interact with the enzyme in a unique fashion that allows for potent binding in a non-traditional paradigm. In addition to the elucidation of their binding profile, we have discovered a pH dependent effect on the binding affinity as a result of the intrinsic pK(a) of these inhibitors and the pH of the BACE-1 enzyme binding assay.
- [Show abstract] [Hide abstract] ABSTRACT: BACE-1 (beta-site amyloid precursor protein cleaving enzyme), a prominent target in Alzheimer's disease drug discovery efforts, was surveyed using Tethering technology to discover small molecule fragment ligands that bind to the enzyme active site. Screens of a library of >15000 thiol-containing fragments versus a panel of BACE-1 active site cysteine mutants under redox-controlled conditions revealed several novel amine-containing fragments that could be selectively captured by subsets of the tethering sites. For one such hit class, defined by a central aminobenzylpiperidine (ABP) moiety, X-ray crystal structures of BACE mutant-disulfide conjugates revealed that the fragment bound by engaging both catalytic aspartates with hydrogen bonds. The affinities of ABP fragments were improved by structure-guided chemistry, first for conjugation as thiol-containing fragments and then for stand-alone, noncovalent inhibition of wild-type (WT) BACE-1 activity. Crystallography confirmed that the inhibitors bound in exactly the same mode as the disulfide-conjugated fragments that were originally selected from the screen. The ABP ligands represent a new type of nonpeptidic BACE-1 inhibitor motif that has not been described in the aspartyl protease literature and may serve as a starting point for the development of BACE-1-directed Alzheimer's disease therapeutics.
Article: Evolution of Tertiary Carbinamine BACE-1 Inhibitors: A beta Reduction in Rhesus CSF upon Oral Dosing[Show abstract] [Hide abstract] ABSTRACT: Incorporation of an isonicotinic core containing a P3 methylcyclopropyl group into our previously reported ox-adiazolyl tertiary carbinamine based BACE-1 inhibitors has led to the identification of the exquisitely potent inhibitor 6, which displays good permeability and low susceptibility to the P-gp efflux pump. Upon co-dosing with CYP 3A4 inhibitor ritonavir, tertiary carbinamine 6 was found to be orally bioavailable. Following twice daily oral administration to monkeys, it was shown to penetrate the CNS and lower Aβ42 levels in the CSF by >40% over the course of a 3 day experiment. Further structural improvements aimed at optimization of pharmacokinetics and brain penetration will be the subject of future work, as will studies of the impact of central BACE-1 inhibitor-mediated Aβ42 lowering on cognition.
Article: Identification of a small molecule β-secretase inhibitor that binds without catalytic aspartate engagement[Show abstract] [Hide abstract] ABSTRACT: A small molecule inhibitor of beta-secretase with a unique binding mode has been developed. Crystallographic determination of the enzyme-inhibitor complex shows the catalytic aspartate residues in the active site are not engaged in inhibitor binding. This unprecedented binding mode in the field of aspartyl protease inhibition is described.
Article: First Demonstration of Cerebrospinal Fluid and Plasma A Lowering with Oral Administration of a -Site Amyloid Precursor Protein-Cleaving Enzyme 1 Inhibitor in Nonhuman Primates[Show abstract] [Hide abstract] ABSTRACT: beta-Site amyloid precursor protein (APP)-cleaving enzyme (BACE) 1 cleavage of amyloid precursor protein is an essential step in the generation of the potentially neurotoxic and amyloidogenic A beta 42 peptides in Alzheimer's disease. Although previous mouse studies have shown brain A beta lowering after BACE1 inhibition, extension of such studies to nonhuman primates or man was precluded by poor potency, brain penetration, and pharmacokinetics of available inhibitors. In this study, a novel tertiary carbinamine BACE1 inhibitor, tertiary carbinamine (TC)-1, was assessed in a unique cisterna magna ported rhesus monkey model, where the temporal dynamics of A beta in cerebrospinal fluid (CSF) and plasma could be evaluated. TC-1, a potent inhibitor (IC(50) approximately 0.4 nM), has excellent passive membrane permeability, low susceptibility to P-glycoprotein transport, and lowered brain A beta levels in a mouse model. Intravenous infusion of TC-1 led to a significant but transient lowering of CSF and plasma A beta levels in conscious rhesus monkeys because it underwent CYP3A4-mediated metabolism. Oral codosing of TC-1 with ritonavir, a potent CYP3A4 inhibitor, twice daily over 3.5 days in rhesus monkeys led to sustained plasma TC-1 exposure and a significant and sustained reduction in CSF sAPP beta, A beta 40, A beta 42, and plasma A beta 40 levels. CSF A beta 42 lowering showed an EC(50) of approximately 20 nM with respect to the CSF [TC-1] levels, demonstrating excellent concordance with its potency in a cell-based assay. These results demonstrate the first in vivo proof of concept of CSF A beta lowering after oral administration of a BACE1 inhibitor in a nonhuman primate.
Article: Discovery and X-ray Crystallographic Analysis of a Spiropiperidine Iminohydantoin Inhibitor of β-Secretase ‡[Show abstract] [Hide abstract] ABSTRACT: A high-throughput screen at 100 microM inhibitor concentration for the BACE-1 enzyme revealed a novel spiropiperidine iminohydantoin aspartyl protease inhibitor template. An X-ray cocrystal structure with BACE-1 revealed a novel mode of binding whereby the inhibitor interacts with the catalytic aspartates via bridging water molecules. Using the crystal structure as a guide, potent compounds with good brain penetration were designed.
Article: O1-04-02: Significant Aβ lowering in CSF and plasma after oral administration of a potent small molecule BACE1 inhibitor in non-human primates
Article: P3-094: Three novel CSF assays expand a core panel of CSF biomarkers: BACE activity, oligomeric Aβ and homocysteine assessed in pathologically confirmed Alzheimer subjects within the Oxford project to investigate memory and aging (Optima) cohort
Article: Strategies toward improving the brain penetration of macrocyclic tertiary carbinamine BACE-1 inhibitors[Show abstract] [Hide abstract] ABSTRACT: This letter describes replacements for the P3 amide moiety present in previously reported tertiary carbinamine macrolactones. Although P-gp efflux issues associated with these amide-macrolactones were solved and full brain penetration was measured in one case, potency was compromised in the process.
Article: Discovery of Isonicotinamide Derived β-Secretase Inhibitors: In Vivo Reduction of β-Amyloid[Show abstract] [Hide abstract] ABSTRACT: beta-Secretase inhibition offers an exciting opportunity for therapeutic intervention in the progression of Alzheimer's disease. A series of isonicotinamides derived from traditional aspartyl protease transition state isostere inhibitors has been optimized to yield low nanomolar inhibitors with sufficient penetration across the blood-brain barrier to demonstrate beta-amyloid lowering in a murine model.
- [Show abstract] [Hide abstract] ABSTRACT: (Chemical Equation Presented) Structure-based drug design was used to incorporate the traditional hydroxyethyl amine aspartyl protease inhibitor motif into 2,3,5-substituted imidazolidin-4-one structures with good BACE-1 enzyme inhibitory potency. These compounds represent a promising drug target for Alzheimer's disease-modifying therapy and are therefore of interest to the medicinal chemistry community.
- [Show abstract] [Hide abstract] ABSTRACT: This Letter describes the design and synthesis of tertiary carbinamine macrocyclic inhibitors of the beta-secretase (BACE-1) enzyme. These macrocyclic inhibitors, some of which incorporate novel P2 substituents, display a 2- to 100-fold increase in potency relative to the previously described acyclic analogs while affording greater stability.
Article: Cover Picture: Design and Synthesis of 2,3,5-Substituted Imidazolidin-4-one Inhibitors of BACE-1 (ChemMedChem 7/2007)
Article: β-Secretase (BACE-1) inhibitors: Accounting for 10s loop flexibility using rigid active sites[Show abstract] [Hide abstract] ABSTRACT: BACE-1 is a flexible enzyme with experimentally determined motion in the flap region, the catalytic aspartates, and the 10s loop. Four in-house crystallographically determined complexes of tertiary carbinamine inhibitors revealed 10s loop motion in the S-3 pocket. These X-ray structures were used to correlate K-i values, which span over five orders of magnitude, with the calculated interaction energy, using the Merck Molecular Force Field for a series of 19 tertiary carbinamine inhibitors. (c) 2006 Elsevier Ltd. All rights reserved.
- [Show abstract] [Hide abstract] ABSTRACT: We describe the discovery and optimization of tertiary carbinamine derived inhibitors of the enzyme beta-secretase (BACE-1). These novel non-transition-state-derived ligands incorporate a single primary amine to interact with the catalytic aspartates of the target enzyme. Optimization of this series provided inhibitors with intrinsic and functional potency comparable to evolved transition state isostere derived inhibitors of BACE-1.


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In spite of all of the critiques and pessimism of the author and commentators, I think it will be nice to have the gash in the middle of the city covered. Glad that the city was smart enough to put together a credible proposal for the $19 million.
Cheese and rice, look into this project a little deeper.
Housing is irrelevant to this project because it is federally funded through a TIGER grant, which comes through the Dept. of Transportation specifically for transit projects. This cap project has been an idea for years and the DOT didn't initially see it relevant as a transit project at first; it took several years of applications by state representatives to coherence agreement.
It is not just a slab of concrete. The proposal will build up terra and support vegetation in a highly exposed, hot and uncomfortable link between Uptown, the Hill, and Downtown.
The 28-acres "someday, maybe" will be developed; wouldn't creating physical access, outdoor congregation space, preformative space, and commercial space that bridges the largest obstruction to existing vibrance create a more inciting and commercially viable prospect for the Lower Hill? Developmental energy will come from Downtown toward the Hill, regardless of how ideal it seems to be in the inverse.
And FYI: it's LaQuatra Bonci Associates and Walter Hood is a landscape architect, not an architect.
Clear-eyed analysis beats blind Chamber-of-Commerce cheerleading every time. And let's not forget all of the Hill District connections to Uptown (the Fifth/Forbes corridor). Knitting together those two neighborhoods would be a boost to both Oakland and Downtown.
People keep asking me about the $19 million for the Hill District. The Hill District did not get $19 million. The money is another subsidy for the Penguins. In addition to the more than $750 million they have already received.
$19 million more for the Penguins no money for the Curtain Call community project promised in 2009.
The Hill community continues to be this organized force to fight back against this terrible plan. The community has already developed a plan and the city, SEA, and Penguins will not be able to continue to ignore us for long. But I also tired of waiting and doing whatever I can to continue to work with amazing group of people in the Hill to come up with community solutions to revitalize and make the community economically strong while preserving the historic and cultural legacy of the Hill! The restoration of the August Wilson House (#AWHouse) is a great example of a grass root community solution to counter act the city's horrible urban redevelopment plans and a catalyst for positive change in a community (such as the Hill) that have been economically dis-invested for decades through racism and bad policy making by the powers that be. I will not sit on the sideline and let history repeat itself! So the fight continues and I believe that WE CAN WIN!!!
It seems that this is a case of the perfect being the enemy of the good. It is without doubt a good thing to cover even just this one block of the highway rather than to leave its entire length as an open scar. Yes, it would probably be better if the open space could be further up the slope and immersed in the center of the Lower Hill development; that would allow this parcel to become a denser mixed-use development, bridging the divide between Golden Triangle and Lower Hill programmatically and from a massing standpoint. Sadly, the funding for this project cannot be used flexibly, so it is rather a take it or leave it proposition. I'll take it and count it as a gain for the city overall.
The 2009 Greenprint referenced here is a plan for Hill District development that is smart and sensitive to both the environment and to the Hill's history and culture. It was created in a deeply collaborative process with Hill residents, a process facilitated by the Hill House. The author, architect Walter Hood, has every bit of the credentials of LaQuatra Bonci Landscape Architects, leading us to ask, Why is the community's own plan being ignored by the City? This is our chance to correct historic wrong-doing to an entire community- and it's a golden opportunity that won't come around again anytime soon.
connecting the residentiwl community withits neihboring communities needs to be considered as priority. Building infrastructure, fundung home loans, 2nd mortgages and grants to revitalize the residential properties, priority. Tax breaks, loans and grants forthe commercisl area and building new commercial spaces all priorities. Connection could occur by creating attractive avenues to oass into to2n. But perhaps a priority better suited for succesful rejuvenation is creating valuable access into the hill and destinations that attract all city dwellers.
The rehabilitation and reimagining of the recently reopened August Wilson Park (formerly Cliffside) has been a project of the Pittsburgh Parks Conservancy, City of Pittsburgh's Departments of Public Works and City Planning, and Hill House Association. Extensive and honest community conversations and input were key components of the design, planning, construction, and reopening of August Wilson Park. The joy of the community and all involved was clearly evident at the park's reopening event, and was indeed a wonderful thing to see.
How in the world did they get $19 million to build a giant concrete thing no one needs when human beings and small local businesses are being forced out of East Liberty and the Hill needs rebuilding?!? Connecting is all well and good, but how about emphasizing more PROTECTING our people?!?


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Solutions for Chapter 24
Assume you have created a multiview drawing but must move two views farther apart to provide room for dimensions. You could best accomplish this by ____.
a. using the Move command to visually move one view
b. using the Move command with OSNAP to ensure PICKing the correct object feature
C. using the Move command with Polar Snap and Polar Tracking to assure orthogonal alignment and regular interval movement
d. using the Scale command to reduce the size of the views
(Pg 621) You can invoke the Move command; select the entire view with a window or other option, and "slide" the entire view outward. Polar Tracking ensures proper orthogonal alignment. Polar Snap forces the movement to a regular increment so the coordinate points of the geometry retain a relationship to the original points.


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Katie Drager - Associate Professor in Sociolinguistics
In addition to teaching, I am director of the Sociolinguistics Lab, co-director of the Charlene Sato Center for Pidgin, Creole and Dialect Studies, and convener of the In-Group and co-convener of Da Pidgin Coup.
Please note that I will be on sabbatical beginning Spring 2016, so incoming students are expected to work with other faculty and focus on coursework while I am away. I am especially interested in working with students on sociolinguistic variation in indigenous and minority languages and students who are interested in using experimental methods to answer questions about phonetics, lexical access, and social meaning.
Katie Drager


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Definition of sled in English:
chiefly North American
1A vehicle, typically on runners, for conveying goods or passengers over snow or ice, either pushed or pulled, or drawn by horses, dogs, or a motor vehicle.
Example sentences
- Mr Cooney, who already holds the Duke of Edinburgh Gold Award, has had to pull a 200 lb sled across the snow and ice.
- A covered carriage with sled runners pulled by four strong horses is awaiting its passengers.
- She places whatever she needs in a snow sled and pulls it wherever she needs to go.
1.1A small lightweight vehicle, either on runners or having a smooth bottom surface, used for sliding downhill over snow or ice.
Example sentences
- They hadn't been able to get their hands on sleds, but a sleigh ride was always fun on a snowy evening.
- The day of the party promises mittens and hats, mufflers and ski pants, toboggans and sleds.
- We trudged through the snow for a good half hour to make it to the hardware store where we examined all the sleds and finally settled on a long bright orange plastic toboggan.
1.2 another term for snowmobile.
verb (sleds, sledding, sledded)[no object] (usually go sledding)
Travel or slide downhill over snow on a sled: I know my kids would love to have one last snowstorm to build a snowman and go sledding the two sledded down a snow-covered hill
More example sentences
- This foam board with a slick-plastic belly is superquick when running straight - a feeling enhanced by sledding head first, your chin just an inch or so off the snow.
- My cousins and I went sledding, and they were making me laugh - so much that I fell onto my sled backward as it started to glide down the hill.
- On February 6, I was sledding with my sons when I vaguely heard an ambulance go by.
Middle English: from Middle Low German sledde; related to the verb slide.
Words that rhyme with sledabed, ahead, bed, behead, Birkenhead, bled, bread, bred, coed, cred, crossbred, dead, dread, Ed, embed, Enzed, fed, fled, Fred, gainsaid, head, infrared, ked, lead, led, Med, misled, misread, Ned, outspread, premed, pure-bred, read, red, redd, said, samoyed, shed, shred, sked, sped, Spithead, spread, stead, ted, thread, tread, underbred, underfed, wed
For editors and proofreaders
Syllabification: sled
Definition of sled in:
What do you find interesting about this word or phrase?
Comments that don't adhere to our Community Guidelines may be moderated or removed.
= trending


text:
Northern Virginia Soil and Water Conservation District (NVSWCD)
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- Report: #110271
Report - Rebuttal - Arbitrate
Complaint Review: MWI*SIMPLE ESCAPES2
MWI*SIMPLE ESCAPES22803 AVE H APT#1 KEARNEY, Nebraska U.S.A.
MWI*SIMPLE ESCAPES2 ripoff credit card has been charged KEARNEY Nebraska
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Date: 1900 ca.
Description: Main factory with South Foundry in lower left. Lake Michigan is in the background. Later the Allis-Chalmers Manufacturing Co.
Date: 1921-09-01 ca.
Description: Numerous tents with farm machinery and technology with the colosseum in the background, presumably the Wisconsin State Fair.
Description: Letterhead of the Phillip Best Brewing Company of Milwaukee, Wisconsin, with three separate proscenium views of the Empire Brewery, the South Side Brewery,...
Date: 1890 ca.
Description: Section of the factory at a crossroads with road construction workers outside. Name of company visible on building.
Date: 1938-10-28
Description: Man inspecting fish hung up to dry in a yard on Jones Island.
Date: 1938
Description: Elevated view of a boat owned by Julius Dettloff docked along the edge of a river. The boat was powered by an International PD-40 power unit; in the backgr...
Description: Crowds of individuals at the fair, presumable the Wisconsin State Fair.
Date: 1953-08-26
Description: Alice in Dairyland, Mary Ellen Jenks, stands with a cow on a float representing the Golden Guernsey Dairy Co-op in the Dairy Parade at the Wisconsin State...
Description: View west from Mitchell Block of warehouses, industrial buildings and a church in the background. In the foreground is a waterway with a schooner and two s...
Description: A group of men sit and stand in front of Old City Hall (built 1860).
Description: Elevated view of bay shoreline, with dwellings along the bank. A few boats are in the river. In the background is a factory with a smokestack and railroad...
Description: Pabst Theater Building at E. Wells and N. Water street. The Hotel Blatz is on the left.
Date: 1920-09-01 ca.
Description: Crowds of individuals at the fair, presumably the Wisconsin State Fair.
Description: Logo of the Milwaukee Malting Company from a memohead printed by the Wisconsin Bank Note Company, Milwaukee, with a golden sun emerging from grey clouds, a...
Date: 1921-07-31 ca.
Description: Crowds of individuals along South Shore Beach in the Bay View neighborhood. Some individuals are swimming while others are sitting on the grass and sand....
Date: 1940
Description: This map is pen and ink on paper and is 1 map consisting of 12 sheets. This map includes a numbered key labeling each area, all of which are represented...
Date: date unknown
Description: Two visible steamboats, looking up the Milwaukee River from the north bank, near the foot of the N. Milwaukee Street. Both steamboats are of the Goodrich T...
Description: Milwaukee Arena on Kilbourn Avenue. There is a poster for Sonja Henie on the side of the building.
Date: 1907 ca.
Description: This map shows ward numbers, streets, railroads, electric car lines, parks, steam railways, section numbers, Lake Michigan and one mile concentric circles...
Date: 1946
Description: Members of local 18 United Gas, Coke and Chemical of the C.I.O. picketing in a small circle on a wide downtown sidewalk. Two men hold signs and one reads,...
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Free personalized radio that
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Features of This Trackbasic rock song structures
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call and answer vocal harmony (Antiphony)
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I've had this plugin deactivated forever after an incident (in April or so) where something caused my server to overload -- after I convinced my hosting company to let me into the backend, we turned off all plugins and I only turned on the ones I actually needed to have on.
On 10/12, I turned this plugin back on but did not activate it. I didn't touch any other plugin or make any other changes (not on that day and not in the last 3 months -- just had a baby so I haven't been fussing with the site much).
On 10/18, my host shut me down again, saying that I caused server overload -- 360,000 hits. Unfortunately, this wasn't a mention in the NYT or anything -- I suspect it was just this plugin. Again.
As of 1 AM I've been unsuspended and have gone in and disabled the plugin -- and it seems to be working ok thus far... <fingers crossed>
Anyone else have problems like this? Is it a setting that I screwed up with Super Cache, or should I just find another caching program? (Because I do need one, right?)