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Vyvanse (Lisdexamfetamine Dimesylate): First FDA-Approved Drug for the Treatment of Adults with Binge-Eating Disorder
March 2016, Vol 9, Seventh Annual Payers' Guide - Payers' Guide
Loretta Fala
In the United States, an estimated 30 million individuals have an eating disorder.1 Associated with the highest mortality rate of all mental illnesses, eating disorders claim the lives of nearly 20% of those affected.1
Binge-eating disorder is a serious eating disorder that is characterized by a frequent consumption of unusually large amounts of food within a short, 2-hour period and the uncontrollable urge to continue eating during an episode.2 Approximately 1% to 5% of the US population is affected by binge-eating disorder; 60% of those affected are women, and 40% are men.3
Individuals with binge-eating disorder often eat when they are full or not hungry, eat rapidly during a binge episode, eat until uncomfortably full, or eat alone or in secret. Although the majority of individuals with binge-eating disorder are overweight or obese, someindividuals with the disorder may be of normal weight.2 A binge-eating episode is often followed by feelings of shame, disgust, guilt, or upsetness.2
Binge-eating disorder can have a profound impact on affected individuals. It can lead to obesity and obesity-related medical conditions, including joint problems, heart disease, type 2 diabetes, gastroesophageal reflux disease, and several sleep-related breathing disorders.2 Other complications associated with bingeeating disorder include gallbladder disease, high blood pressure, high cholesterol levels, low selfesteem, social isolation, poor quality of life, and problems functioning at work or in social settings.2,3 Binge-eating disorder is also associated with depression, bipolar disorder, anxiety, and substance abuse disorders.2
Despite the serious health implications associated with eating disorders and the fact that the majority of these disorders can be effectively treated, only 1 in 10 individuals receives treatment.1 Treatment for eating disorders typically requires psychotherapy (eg, cognitive behavioral therapy, interpersonal psychotherapy, or dialectical behavior therapy) and medication.2
Binge-eating disorder should be treated before initiating weight-loss programs, because dieting can trigger binge-eating episodes that interfere with weight loss.2 Although antidepressants and anticonvulsants are sometimes used to help reduce the symptoms of binge eating, until recently, there were no US Food and Drug Administration (FDA)-approved pharmacologic options available to treat binge-eating disorder.2,4
The First Treatment Option for Adults with Binge-Eating Disorder
On January 30, 2015, lisdexamfetamine dimesylate (Vyvanse; Shire), an oral central nervous system (CNS) stimulant, became the first medication to be approved by the FDA for the treatment of adults with binge-eating disorder.4 This approval marks the expanded use of lisdexamfetamine dimesylate, which was previously approved by the FDA in 2007 (also under the name Vyvanse; Shire) for the treatment of patients aged >6 years with attention-deficit/hyperactivity disorder.4 Lisdexamfetamine dimesylate is not indicated for weight loss. The safety and effectiveness of lisdexamfetamine dimesylate for the treatment of obesity have not been established.4,5
Mitchell Mathis, MD, Director of the Division of Psychiatry Products in the FDA's Center for Drug Evaluation and Research, said, "Binge eating can cause serious health problems and difficulties with work, home, and social life. The approval of Vyvanse provides physicians and patients with an effective option to help curb episodes of binge eating.4
The FDA granted lisdexamfetamine dimesylate a priority review based on its intended use to treat a serious disease or condition and its potential to provide a significant improvement over available therapies. As part of its approval, lisdexamfetamine dimesylate must be dispensed with a medication guide that informs patients about the drug's appropriate use and potential risks.4
Dosing and Administration
The recommended starting dose of lisdexamfetamine dimesylate is 30 mg daily, which should be titrated in increments of 20 mg weekly to achieve the recommended target dose of 50 mg to 70 mg daily (Table 1). Patients should be assessed for the presence of cardiac disease before starting treatment with lisdexamfetamine dimesylate.5
Lisdexamfetamine dimesylate is available as a capsule in several dosage strengths, including 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg.5
Lisdexamfetamine dimesylate, a CNS stimulant, is a prodrug of dextroamphetamine. Amphetamines are noncatecholamine sympathomimetic amines with CNS stimulant activity. Amphetamines block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. The parent drug, lisdexamfetamine dimesylate, does not bind to the sites responsible for the reuptake of norepinephrine and dopamine in vitro.5
Clinical Trials Efficacy: Study 10 and Study 11
The efficacy of lisdexamfetamine dimesylate for the treatment of adults with binge-eating disorder was demonstrated in 2 randomized, double-blind, placebo-controlled, phase 3 clinical trials, Study 10 and Study 11.5,6 Study 10 included 374 patients and Study 11 included 350 patients aged 18 to 55 years with moderateto-severe binge-eating disorder.5,6
The diagnosis of binge-eating disorder was confirmed using the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for binge-eating disorder.5 The severity of binge-eating disorder was determined based on having at least 3 binge days weekly for 2 weeks before the baseline visit as well as a Clinical Global Impression severity score of ≥4 at the baseline visit. A "binge day" was defined as a day with at least 1 binge-eating episode, as determined based on the patient's daily binging diary.6
In both studies, the primary efficacy outcome was defined as the change from baseline in the number of binge days weekly at week 12. The baseline was defined as the weekly average of the number of binge days weekly for the 14 days before the baseline visit.6
In Study 10 and Study 11, patients who received lisdexamfetamine dimesylate at doses of 50 mg daily or 70 mg daily had a significantly greater reduction from baseline in the mean number of weekly binge days at week 12 compared with placebo (Study 10, –3.87 vs –2.51, respectively; Study 11, –3.92 vs –2.26, respectively). Table 2 lists the primary efficacy results.
Furthermore, patients who received lisdexamfetamine dimesylate showed greater improvements across key secondary outcomes compared with patients who received placebo, with a higher proportion of patients who improved on the Clinical Global Impression improvement scale, a higher proportion of patients with 4-week binge cessation, and a greater reduction in the Yale-Brown Obsessive Compulsive Scale modified for the binge-eating total score.6
The most common adverse reactions (incidence rate ≥5% and at least twice the rate of placebo) associated with the use of lisdexamfetamine dimesylate in adults with binge-eating disorder were dry mouth (36%), insomnia (20%), decreased appetite (8%), increased heart rate (7%), constipation (6%), feeling jittery (6%), and anxiety (5%).6
In controlled studies of patients aged 18 to 55 years, 5.1% (19/373) of patients who received lisdexamfetamine dimesylate discontinued treatment as a result of adverse reactions compared with 2.4% (9/372) of patients who received placebo. No single adverse reaction led to treatment discontinuation in ≥1% of patients who received lisdexamfetamine dimesylate.6
Drug Interactions: Acidifying and Alkalinizing Agents
Agents that alter urinary pH levels can also alter blood levels of amphetamine. Acidifying agents decrease amphetamine blood levels, and alkalinizing agents increase amphetamine blood levels. The dose of lisdexamfetamine dimesylate should be adjusted accordingly when used together with acidifying or alkalinizing agents.6
Lisdexamfetamine dimesylate is contraindicated in patients with a known hypersensitivity to amphetamine agents or other ingredients in lisdexamfetamine dimesylate. The use of lisdexamfetamine dimesylate is contraindicated with monoamine oxidase (MAO) inhibitors, or within 14 days of the last MAO inhibitor dose.6
Boxed warning. The prescribing information for lisdexamfetamine dimesylate contains a boxed warning stating that CNS stimulants, including lisdexamfetamine dimesylate, have a high risk for abuse and dependence. Patients should be evaluated for the risk of abuse before prescribing lisdexamfetamine dimesylate, and be monitored for signs of abuse and dependence during therapy with lisdexamfetamine dimesylate.6
Serious cardiovascular reactions. Sudden death in children and adolescents with serious heart problems, as well as sudden death, stroke, and myocardial infarction in adults have been reported with the use of lisdexamfetamine dimesylate. This medication should not be used in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, or coronary artery disease.6
Blood pressure and heart rate increases. CNS stimulants cause an increase in blood pressure. All patients should be monitored for hypertension and tachycardia during therapy with lisdexamfetamine dimesylate.6
Psychiatric adverse reactions. Lisdexamfetamine dimesylate may cause psychotic or manic symptoms in patients with no history of psychosis, or an exacerbation of symptoms in patients with preexisting psychosis. Patients should be evaluated for bipolar disorder before taking stimulants.6
Peripheral vasculopathy. Stimulants are associated with peripheral vasculopathy, including Raynaud's phenomenon. Careful observation for digital changes is necessary during treatment with stimulants.5
Pregnancy. Based on animal data, lisdexamfetamine dimesylate may cause fetal harm and should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.6
Nursing. Amphetamines are excreted into human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue lisdexamfetamine dimesylate, taking into account the importance of the drug to the mother.6
Pediatric use. The safety and effectiveness of lisdexamfetamine dimesylate in individuals with binge-eating disorders aged <18 years have not been established.6
Geriatric use. Clinical studies of lisdexamfetamine dimesylate did not include sufficient numbers of patients aged ≥65 years to determine whether they respond differently from younger patients.6
Renal impairment. Because of reduced clearance in patients with severe renal impairment, the maximum dose of lisdexamfetamine dimesylate should not exceed 50 mg daily. The maximum recommended dose of lisdexamfetamine dimesylate in patients with end-stage renal disease is 30 mg daily.6
Gender. No dosage adjustment of lisdexamfetamine dimesylate is necessary on the basis of gender.6
Lisdexamfetamine dimesylate, a CNS stimulant, is the first FDA-approved therapeutic option for adults with binge-eating disorder. Lisdexamfetamine dimesylate modulates the dopaminergic and noradrenergic systems, helping to control episodes of binge eating, which are associated with significant weight gain and other serious health complications.
In 2 identically designed phase 3 clinical trials that included 724 adults, treatment with lisdexamfetamine dimesylate was significantly superior to placebo at decreasing binge-eating days weekly compared with baseline in adults with moderate-to-severe binge-eating disorder. Therapy with lisdexamfetamine dimesylate also demonstrated a greater improvement in key secondary end points, including the Clinical Global Impression improvement scale, compared with placebo.7
1. Eating Disorders Coalition. Facts about eating disorders: what the research shows. www.eatingdisorderscoalition.org/documents/FactsAboutEatingDisorders2014.pdf. Accessed May 9, 2015.
2. Mayo Clinic staff. Diseases and conditions: binge-eating disorder. April 9, 2015. www.mayoclinic.org/diseases-conditions/binge-eating-disorder/basics/definition/con-20033155?p=1. Accessed May 9, 2015.
3. National Eating Disorders Association. Binge eating disorder. www.nationaleatingdisorders.org/binge-eating-disorder. Accessed May 13, 2015.
4. US Food and Drug Administration. FDA expands uses of Vyvanse to treat binge-eating disorder. Press release. January 30, 2015. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm432543.htm. Accessed May 5, 2015.
5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Arlington, VA: American Psychiatric Publishing; 2000.
6. Vyvanse (lisdexamfetamine dimesylate) capsules [prescribing information]. Wayne, PA: Shire US Inc; April 2015.
7. McElroy S, Ferreira-Cornwell MC, Gasior M, et al. Randomized controlled safety and efficacy trials of lisdexamfetamine dimesylate for adults with moderate to severe binge eating disorder. Presented at: American Psychiatric Association 167th Annual Meeting; May 3-7, 2014; New York, NY.
Welcome to the Tenth Annual Payers' Guide to New FDA Approvals
March 2019, Vol 12, Tenth Annual Payers' Guide published on April 15, 2019 in FDA Approvals, Payers' Guide
Lumoxiti (Moxetumomab Pasudotox-tdfk) First CD22-Directed Cytotoxin Approved for Relapsed or Refractory Hairy-Cell Leukemia
Lisa A. Raedler, PhD, RPh
March 2019, Vol 12, Tenth Annual Payers' Guide published on April 15, 2019 in Select Drug Profiles, Payers' Guide
Nuzyra (Omadacycline) Approved for the Treatment of Community-Acquired Bacterial Pneumonia or Acute Bacterial Skin and Skin Structure Infections
Imbruvica (Ibrutinib) plus Rituxan (Rituximab) New Combination FDA Approved for the Treatment of Waldenström's Macroglobulinemia
Olumiant (Baricitinib) Once-Daily Oral Drug Approved for the Treatment of Patients with Moderately to Severely Active Rheumatoid Arthritis


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Fred Smith
Fred Smith was raised in Birmingham where he attended The Altamont School and graduated from Birmingham Southern with a degree in Marketing. Fred obtained his real estate license in 1995 and his broker's license in 1998. Since then he has built and rehabbed numerous houses of his own and has enjoyed assisting others buy and sell real estate. Fred is a Lifetime Member of the Club of Excellence. When he is not selling real estate or leading The Fred Smith Group, Fred, enjoys sailing and spending time with his wife, Holly, 2 daughters, Lily and Isabel, and his son, Darby.
The Fred Smith Group | RealtySouth
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redpajama_set_name: RedPajamaCommonCrawl


View more presentations from Sachin Rekhi.
I'm always interested in improving my development stack in order to maximize productivity, facilitate rapid iterations, and maintain flexibility. Over the years I've periodically iterated my web stack, from a Microsoft-based self-hosted environment, to a PHP-centered world, to finally my present Python\Django stack on top of a cloud platform.
I thought I would detail my current stack and technology choices for those interested. I would also love to hear from you on what you use or if you have any suggested improvements.
Not only does Apple make elegant Mac Book Pro laptops for both portability and to serve as a desktop replacement, but the Mac OS X operating system is terrific for web development, since the underlying Linux OS allows the system to closely mimic my production environment.
Ever since getting my Dell Ultrasharp 24'' monitor, I refuse to do any serious development away from it. The productivity gains from having a large monitor are astonishing and I can't believe I lived without one for so long.
I spend a lot of time listening to music while coding, so this top notch speaker system, Klipsh Quintent III, has become an essential component to my development environment.
While some will rave about the elegance of TextMate as the IDE of choice for Mac (or simply emacs or VI), I've always been a fan of powerful IDEs. (I did work on the Visual Studio team for 2 years before coming to the valley, after all). Eclipse, coupled with the PyDev and Pylint plugins, provides a great development environment for Python. In addition to all the Eclipse productivity features, you get Python specific syntax highlighting, code completion, syntactic analysis from PyDev and semantic analysis from Pylint.
Subversion is my go to version control repository, with svnX as the native Mac client. While Git is the latest craze, I haven't found it's features compelling for my small team. Though Github itself as a hosted Git provider has some compelling features that I have been meaning to try.
While Basecamp or Trac are the tools I most often recommend to young startups for basic project management, I instead use a very simple task manager I built called MonkeySort. It has the 3 things I need and nothing more: lists, prioritization, and task history.
All of my specs, project timelines, feature breakdowns, competitive analysis, overviews, and presentations are produced in Google Docs, including documents, spreadsheets, and presentations. While not as feature-full as Microsoft Office, they provide anywhere access and easy collaboration which are very important to me.
I'm a big supporter of cloud platforms to reduce the administration overhead of deployments as well as increase the flexibility of increasing\decreasing capacity whenever necessary. I've used AWS for my previous startups and continue to use it for my new projects. I've dabbled with Google App Engine as well, but found it too limiting for large applications.
I have a cheap $10/mo shared host running on WebFaction. I use it for hosting my Subversion server. While I could easily do this on AWS, I personally prefer having my development servers separate from my production environment.
I'm excited for the innovation we are seeing in HTML 5. For the first time in a decade we are experiencing the browser wars again. I'm taking advantage of the new HTML 5 capabilities wherever possible (especially on mobile web apps), including offline support, local data storage, canvas, video, and audio components.
I discovered Python while learning Google App Engine. While I've abandoned App Engine, Python has stuck with me as a highly productive and elegant web programming language. The additional benefit of it over PHP is that it is easily usable for non-web code, so I use it for all my queue server and offline processing as well, allowing one elegant language across all my web and non-web components.
Django in my mind is a great compromise between Ruby on Rails and raw PHP programming. RoR has too much magic going on for me under the covers and has somewhat of a take it all or leave it all mentality. Django, on the other hand, is extremely pluggable, allowing you to use individual pieces like the ORM, templates, URL dispatching, etc or to abandon an individual component without throwing out the framework. The flexibility allows you to easily start on the complete stack and switch components as you grow out of them.
I use Apache with mod_wsgi as my app web server for all of my Python\Django code.
Nginx has been a great web server in front of my apache instances for static file serving as well as round robining for distributing server load. Very easy to configure and super fast for these tasks.
CentOS is a complete open source version of Red Hat Enterprise Linux, so it has the robustness and scalability of Red Hat's core operating system. In addition, it's extremely lightweight and perfect for server deployments. I've moved most of my prior Fedora instances (AWS default) to CentOS.
MySQL has been the reliable back-end relational database I've been using for years. Development has been significantly simplified now with Django's ORM, but MySQL is still a crucial piece of the architecture.
memcached has been a relatively new addition to my stack in order to significantly improve the performance of applications that have complex SQL queries behind them. I've also started using it to cache API requests in addition to database query results.
While Amazon provides it's CloudWatch server monitoring solution, it's needlessly expensive and limited in the kind of monitors you can attach. Instead I use Munin, which is completely free and has a rich ecosystem of pluggable monitors that you can add. I use it to track everything from website latency, to memcached usage, to MySQL query usage, to Apache requests, to Nginx load balancing. All visible in one easy to use web dashboard.
It's of course necessary to get real-time alerts when servers are down. I trust Pingdom for this task. I have also been using Cloudkick recently for this and it's additional cloud platform server monitoring functionality.


Like many modern cars, Tesla vehicles have cameras all around them to power advanced driving aids. The company regularly rolls out new features through updates which leverage existing hardware to make lives easier for owners. The "Sentry Mode" is going to be one such feature. It will enable the cars to record video in 360 degrees.
Tesla CEO Elon Musk teased this feature in response to a tweet in which a Tesla owner had lamented about finding a dent on their Tesla. Musk was tagged in the tweet which expressed a wish for Tesla vehicles to offer a 360 dash cam feature.
Musk responded simply by saying that Tesla Sentry Mode will be coming soon for all cars with Enhanced Autopilot. That means that this feature will be available on all Tesla vehicles with Autopilot 2.5 Hardware. The hardware already allows for 360 degree surround camera views so it wouldn't really be difficult to offer a dash cam feature.
There are little details on how this feature will actually work. Whether the 360 dash cam feature will be always on or if it will only be switched on once the car detects an impact or break-in. Musk didn't elaborate on these points but it's likely that he'll follow up with more information once the feature is close to being rolled out.


Experienced FMCG professional with 28 years of Marketing, Strategy and General management experience. Worked at respected companies like Colgate Palmolive, Parle Products, Johnson & Johnson, Samsung and Zydus Wellness. Handled domestic leadership roles (VP marketing- Consumer division, J&J – India) and international assignments (Regional Marketing Director – Asia-Pacific, J&J Singapore). Last role was Managing director of Zydus Wellness Limited, a publicly listed FMCG company, part of the larger Zydus Cadila group. Currently working as an independent business and strategy consultant, partnering with International Private Equity firms and teaching at MICA.


These Guides have 16 pages and cover a brief history, disassembly, and reassembly of the firearm. Over 20 high resolution illustrations and pictures guide you through the entire process. Remington, Colt, Glock, Ruger, Mossberg, and countless other manufacturers are covered.
• Cardstock cover. Bright white paper.


The terms 32-bit and 64-bit refer to the way a computer's processor (also called a CPU), handles information. The 64-bit version of Windows handles large amounts of random access memory (RAM) more effectively than the 32-bit version. Follow the steps below to find out if your PC is running the 32-bit or 64-bit version of Windows and what edition of Windows is on your PC.
If you don't see "x64 Edition" listed under System, you're running the 32-bit version of Windows XP.
The edition of Windows XP you're running is displayed under System near the top of the window.


text:
Q: Accesing a BLoC using getit instead of context not working I am trying to access a BLoC instance without actually using the context, but getIt instead. The versions I have are:
  flutter_bloc: ^8.1.1
  injectable: ^2.1.0
  get_it: ^7.2.0
  injectable_generator: ^2.1.3

I have the BLoC registered in getit using "@injectable".
The problem goes like this:
Firstly, I provide the bloc using:
BlocProvider(
      lazy: false,
      create: (context) => getIt<BlocA>(),
    ),

I am trying to use:
getIt<BlocA>().add(
               BlocAEvent.started(),
             );

Lets say that on started event I log something in the console and emit a new state, when I use getIt to add the started event, it will actually do something and log the started event in the console.
But, if I am using a BlocBuilder with BlocA in the UI, that Builder will not actually get the new emitted state. So, the log happens, but the emit after the log is not caught by BlocBuilder, which will remain to its initial state. It is clear to me that getIt does something to another instance of BlocA, cause if I use context to emit BlocA Started event everything works normally and BlocBuilder gets the new emitted state after the log.
Why is it not working? I am providing getIt() not just BlocA. (the stream of states from getIt() and the stream from context.read() have different hashCodes also)

A: If you want to listen to an event, include everything in a BlocListener. In this way, you will have a listener for each of the states that you emit, thus guaranteeing and validating when it is a state that you want.
For example:
return BlocListener<DistributionCenterBloc, DistributionCenterState>(
        listenWhen: (previous, current) =>
            previous.success != current.success ||
            previous.errorResponse != current.errorResponse,
        listener: (context, state) {
          if (state.success != '') {
            audioCache!.play(audioCorrect);
          }

In this way, I validate what the states are and make the pertinent decision for each one of them.

redpajama_set_name: RedPajamaStackExchange


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UK and Dutch athletes do not bring their cell phones and laptops to Beijing Winter Olympics
According to the Dutch newspaper Volkskrant, the national team will provide competitors and delegates support experts say cell phones and laptops will be destroyed once they return from China. According to the Guardian newspaper, the English will provide equipment to athletes and staff, but say it is up to members to decide whether or not to use it.
According to Keert Slot, a spokesman for the Dutch group, "The importance of cyber security has grown over the years. [em qualquer país]. But China has completely shut down its Internet, which makes a certain case. The Chinese government has been accused of not openly monitoring non-Chinese citizens entering its territory and of implementing a large surveillance system for its population.
The Beijing 2022 Winter Olympics will be held from February 4 to February 20. Countries such as the United States, the United Kingdom, Canada and Australia have already declared "diplomatic boycotts", meaning the absence of government officials in sports. The official accusation is that the fight against human rights abuses in the Xinjiang region is against the Uyghurs, as well as against the political repression in Hong Kong and Taiwan. The Chinese government says the boycott includes propaganda and geopolitical and geopolitical interests.
See also The United States has said it wants to "enhance" trade ties with Uruguay
Previous A portrait of Boris Johnson, who is attending a party for the 2nd time, is scratched in the middle of Lockdown, UK.
Next The United States promises new measures against supply problems


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Datacenter/
Imaging System Deals Tropicana a Winning Hand
Signature verification is just the beginning for an imaging system recently installed at the casino and resort hotel
Gambling, by definition, involves taking risks. But one thing for sure—if you're a patron at a casino, you expect the dealer to play by the rules, and you expect the casino to pay up if you win. Likewise, if you say you're good for a couple of grand, the casino expects you to mean it. But just to be on the safe side, they make you sign for it. And, they have ways to make sure that this signature is, in fact, yours, that the money you say you have, you really do have, and that if you lose, that they get paid. The mastermind behind the technology used to accomplish these kinds of tasks? The casino's IT manager.
Take, for example, the Tropicana Casino and Resort. A subsidiary of Aztar Corp., the Tropicana is the biggest hotel in New Jersey with 1,624 rooms and suites, and a 124,000 square foot casino. Although it is the primary convention hotel in Atlantic City, with the facilities to host large meetings and exhibits, the casino is Tropicana's primary business unit.
In the summer of 1999, Tropicana replaced its IT systems, migrating core applications from a non-Y2K compliant IBM mainframe to an AS/400 Model 640 2239, running OS/400 V4R3. Among the mainframe applications that had to be replaced on the AS/400 was a signature display function, a limited, single-purpose imaging system used for verifying the signatures of casino patrons on casino credit applications, or markers.
"In 1998, we considered various alternatives," says Don Kneisel, executive director of IT. "We could have gone with a very specific solution that would have been a one-to-one replacement for the old signature display, but I didn't want something so narrowly focused. We were rebuilding IT from the ground up. I wanted to buy a product that would last into the future, so I went looking for an imaging system."
With Y2K approaching, Kneisel was under some hard deadlines. After examining available products that were proven to work in the casino industry, he came up with a short list of candidates. For its hotel business, Tropicana had already acquired the Lodging Management System, a hospitality management product from Inter-American Data (Lawrenceville, Ga.), with computer output laser disk (COLD) technology for optical storage. Kneisel found that Inter-American also had a sister product, an imaging system called e.FileClerk Web.
The e.FileClerk Web product offered several advantages. First, the product was less expensive than its competitors. Second, Kneisel saw a benefit in going with one vendor. And third, the product offered flexibility, such as the ability to add workflow functionality. Although the product is not currently being used for Web access, it has that capability if Tropicana chooses to move toward e-business.
"I wanted a product I could grow with," Kneisel says. "I bought it for one particular application, signature verification. But, in addition to that one application, I will have the ability to use it in many other areas, like human resources or typical accounting applications."
Its current use as a signature verification system is simple. Casino customers can apply for a line of credit from Tropicana, which for some customers avoids the necessity of bringing a large amount of cash to the casino. In the casino credit office, off the gaming room floor, a customer fills out credit application forms. There, the customer's driver's license with signature is scanned into the system.
When the customer wants to withdraw money against his account he goes to a pit clerk on the floor and requests the funds. An AS/400-based application completes the transaction and prints the marker that the customer signs. His signature is looked up on e.FileClerk, which displays the customer's signature, driver's license and credit application on a monitor at the pit clerk's station, and, once verified, the customer gets his money. If the customer is lucky, he can pay off the marker the same night. If not, the funds are withdrawn from his bank account.
Kneisel sees uses for e.FileClerk that go beyond signature verification, but his plans have been delayed by the migration from the mainframe. "Now it's almost a wash," he says. "I replaced something I had with something new, one-for-one. But the value lies in the future, with its potential to do much more. We haven't been able to do more yet because of the workload we've had."
Kneisel is still in the process of moving reports from an online report viewing system that was on the mainframe, from mainframe DASD to the COLD Lodging Management System to be stored on optical disk. The optical storage system will be shared by both the Lodging Management and the imaging systems and will eventually total 13 2.5GB platters, or 52.5GB. "Compared to the mainframe, I'll use a lot less disk space to store reports," he says.
Once the migration off the mainframe is complete, Kneisel plans to use e.FileClerk to replace a microfilm archiving system that has been used to satisfy a requirement by the State of New Jersey that Tropicana save an image or photograph of all checks before they are deposited in the company's accounts. A natural application for imaging, e.FileClerk will be used to scan checks and save the images to optical disk. Integration with the human resources and accounting applications in the core Lodging Management system is also planned.
According to Kneisel, by eliminating paperwork and centralizing storage, accuracy and the ability to share information will improve. Tropicana will have the ability to add applications as the business evolves without changing its infrastructure or adding staff, all of which promise to add up to significant dollar savings.
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K L Carraway
Mechanism of concanavalin A-induced anchorage of the major cell surface glycoproteins to the submembrane cytoskeleton in 13762 ascites mammary adenocarcinoma cells.
G Jung, R M Helm, C A Carraway, K L Carraway
Concanavalin A (Con A)-induced anchorage of the major cell surface sialoglycoprotein component complex (ASGP-1/ASGP-2) was studied in 13762 rat mammary adenocarcinoma sublines with mobile (MAT-B1 subline) and immobile (MAT-C1 subline) cell surface Con A receptors. Treatment of cells, isolated microvilli, or microvillar membranes with Con A resulted in marked retention of ASGP-1 and ASGP-2, a Con A-binding protein, in cytoskeletal residues of both sublines obtained by extraction with Triton X-100 in PBS. When Con A-treated microvillar membranes were extracted with a buffer containing Triton X-100, the sialoglycoprotein complex was found associated in the residues with a transmembrane complex composed of actin, a 58,000-dalton polypeptide, and a cytoskeleton-associated glycoprotein (CAG), also a Con A-binding protein, in MAT-C1 membranes, and of actin and CAG in MAT-B1 membranes. Untreated membrane Triton residues retained very little ASGP-1/ASGP-2 complex. Association of the sialoglycomembrane complex and the transmembrane complex was also demonstrated in Con A-treated, but not untreated, microvilli by their comigration on CsCl gradients. Association of both complexes with the cytoskeleton of microvilli was shown by sucrose density gradient centrifugation. A fraction of the polymerized actin comigrated with the transmembrane complex alone in the absence of Con A and with both the transmembrane complex and the sialoglycoprotein complex in the presence of Con A. From these results we propose that anchorage of the sialoglycoprotein complex to the cytoskeleton on Con A treatment occurs by cross-linking ASGP-2, the major cell surface Con A-binding component, to CAG of the transmembrane complex, which is natively linked to the cytoskeleton via its actin component. Since Con A-induced anchorage occurs in sublines with mobile and immobile receptors, the anchorage process cannot be responsible for the differences in receptor mobility between the sublines.
Membrane-associated actin from the microvillar membranes of ascites tumor cells.
K L Carraway, R F Cerra, G Jung, C A Carraway
A membrane fraction (MF2) has been purified from isolated microvilli of the MAT-C1 subline of the 13762 rat mammary ascites adenocarcinoma under conditions which cause F-actin depolymerization. This membrane preparation contains actin as a major component, although no filamentous structures are observed by transmission electron microscopy. Membranes were extracted with a Triton X-100-containing actin-stabilizing buffer (S buffer) or actin-destabilizing buffer (D buffer). In D buffer greater than 90% of metabolically labeled protein and glycoprotein was extracted, and 80-90% of these labeled species was extracted in S buffer. When S buffer extracts of MF2 were fractionated by either gel filtration on Sepharose 6 B or rate-zonal sucrose density gradient centrifugation, most of the actin was found to be intermediate in size between G- and F-actin. In D buffer most of the MF2 actin behaved as G-actin. Extraction and gel filtration of intact microvilli in S buffer also showed the presence of the intermediate form of actin, indicating that it did not arise during membrane preparation. When [35S]methionine-labeled G-actin from ascites cells was added to S buffer extracts of MF2 and chromatographed, all of the radioactivity chromatographed as G-actin, indicating that the intermediate form of actin did not result from an association of G-actin molecules during extraction or chromatography. The results of this study suggest that the microvillar membrane fraction is enriched in an intermediate form of actin smaller than F-actin and larger than G-actin.
Effects of cytoskeletal perturbant drugs on ecto 5'-nucleotidase, a concanavalin A receptor.
K L Carraway, R C Doss, J W Huggins, R W Chesnut, C A Carraway
Differences in cell morphology, concanavalin A-induced receptor redistributions, and the cooperativity of the inhibition of 5'-nucleotidase (AMPase) by concanavalin A (Con A) have been investigated in ascites sublines of the 13762 rat mammary adenocarcinoma cells treated with microfilament- and microtubule-perturbing drugs. By scanning electron microscopy MAT-C1 cells exhibit a highly irregular surface, covered with microvilli extending as branched structures from the cell body. MAT-A, MAT-B, and MAT-B1 cells have a more normal appearance, with unbranched microvilli, ruffles, ridges, and blebs associated closely with the cell body. MAT-C cells have an intermediate morphology. Treatment of MAT-A, MAT-B, or MAT-B1 cells with Con A causes rapid redistribution of Con A receptors. Both cytochalasins and colchicine cause alternations in the receptor redistributions. Receptors on MAT-C1 cells are highly resistant to redistribution, even in the presence of cytoskeletal perturbant drugs. The cooperativity of the inhibition of AMPase by Con A was investigated in MAT-A and MAT-C1 cells. Untreated cells exhibit no cooperativity. If either subline is treated with colchicine, cytochalasin B or D, or dibucaine, cooperativity is observed. Lumicolchicine has no effect. Theophylline or dibutyryl cyclic AMP prevents the effects of either colchicine or cytochalasin. The concentration required for half-maximal induction of cooperativity is 0.3--0.4 microM for both colchicine and cytochalasin D, which is in the appropriate range for specific microtubule and microfilament disruptions. The effectiveness of the cytochalasins (E greater than D greater than B) is consistent with their known effects on microfilaments. No direct correlation was observed between the induction of cooperativity and drug-induced changes in Con A receptor redistribution or cell morphology. The morphology of MAT-A cells is grossly altered by cytochalasins or dibucaine and somewhat less by colchicine. MAT-C1 cells exhibit more minor alterations in morphology as a result of these drug treatments. The results of this study indicate that the inhibition of AMPase, which is a Con A receptor, is a different process from the redistribution of the bulk of the Con A receptors, possibly short range membrane interactions rather than global effects on the cell.


text:
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Featured / MMA / UFC
UFC 246 Main Event Preview
by Alan_McDonald25 · January 16, 2020
The first card of the new year and the new decade certainly has potential to bring excitement. Not just with the return of Conor McGregor vs all-time action hero Donald "Cowboy" Cerrone, but we have a solid main card and undercard, with all time greats, up and coming prospects, and fringe contenders looking to break through into contention. This is the UFC 246 Main Event Preview.
The Notorious One has Returned
Through all the controversy and the chaos that comes with his name, it is admittedly nice to see McGregor back. His story is very well documented at this point. McGregor started out at featherweight and suffered through brutal weight cuts to gain a massive size and power advantage. He used his combination of charismatic mic skills and high level in cage skills to make a quick rise to the 145-pound belt. He then captured it with a quick knockout over then-champion Jose Aldo. Then came two classic fights with Nate Diaz, where they split the series 1 – 1. After that, most memorably, he made history by becoming the first simultaneous two division champion in UFC history. He did so with a dominant 2nd round knockout over Eddie Alvarez.
A brief run in boxing to fight Floyd Mayweather, which McGregor essentially talked into existence, didn't do a whole lot except make Conor a lot of money. He was clearly outboxed by Mayweather and lost via 10th round TKO. Then finally, after about two years away, McGregor returned to face the newly-crowned lightweight champion Khabib Nurmagomedov. Khabib was, for a long time, believed to be the worst match-up in the division for McGregor. The beliefs were proved right, as Conor was soundly dominated by Khabib en route to a 4th round submission loss. The brawl afterwards and some legal troubles has kept McGregor out ever since. Maybe with this return, we will finally see the return to form for "The Notorious One". Luckily, Cerrone should be the perfect opponent to see where McGregor is at.
Spotlight Finally Shines Bright for Cowboy
For his 50th pro fight, it is nice to see Cerrone get a massive spotlight like this one. Through all the ups and downs, Donald Cerrone is still here. At the time of this writing, he's still in the top 5 of the division at 155. Across two divisions, Cowboy has been one of the most reliable and well-rounded action heroes. He's done so while maintaining a consistent stance at the top level of the division for the better part of the last decade. From his 8-fight win streak that brought him a 155 pound title shot, only to get smoked quickly by then champion Rafael Dos Anjos. To his move up to 170, where, initially, he looked better than ever, but then finally ran into opponents he could no longer scare off from relentlessly pressuring him. That gave way to a career-worst 3-fight losing streak and ultimately a 6 – 4 record at welterweight when it was all said and done.
After a nice win over Mike Perry, he returned to 155. He proceeded to reintroduce himself with a 2nd round TKO over the up and coming Alexander Hernandez. He followed that up with a five round beating of Al Iaquinta. Tony Ferguson was too much to overcome, and Justin Gaethje flat out blew Cerrone out of the water in September. Admittedly, it is tough to say whether or not Cerrone is finally slowing down for good. It could be due to of the level of competition he's been up against. A championship doesn't seem to be in the cards for Cowboy, but who knows? With a win here over McGregor, he may jump the queue for one last shot at the championship.
This should be McGregor's fight to lose on paper, but this would be much easier to pick if I was sure where his head was at. If he comes in half-hearted, looking for a payday, then Cerrone should be able to pick at him from range and win a nice decision. However, I tend to put him in the same category as Nate Diaz where "If he wasn't motivated, he wouldn't fight.", so I'm expecting him to come back ready to go.
Cerrone planning a stand-up fight is a nice thing to say in front of the camera, but it will be interesting to see if he sticks to that plan as the fight progresses. If this does stays on the feet the whole time, then McGregor should be able to use his speed and accuracy to tag Cerrone and throw off his rhythm. Cerrone has seemed to want to break his own patented slow starts in the last two, but that has just run him into strikes from both Ferguson and Gaethje. With McGregor's countering ability, the same thing will probably happen if Cerrone rushes Conor.
If this goes longer than two rounds, things will get interesting and potentially swing in Cowboy's favour. However, it's hard to say that it will get that far. I don't think it will be quite as quick as the Gaethje fight. However, the pick is still McGregor via second-round stoppage.
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Workforce International, Traffic Control Equipment & Services, listed under "Traffic Control Equipment & Services" category, is located at 4/ 107 Marconi Crs Kambah ACT, 2902, Australia and can be reached by 0262321830 phone number. Workforce International has currently 0 reviews.
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• What is a locksmith, and what do you do all day?
We unlock things that may be locked either due to damage, lost key/credential, or other circumstances; rekey houses, businesses, government buildings, replace lost keys, copy keys,fix doors, install new locks or repair existing ones, service, open and repair safes and vaults, repair broken locks on cars/houses/etc., design and install master key systems, install electronic locks, door closers, exit devices, program keys & remotes to cars, reprogram "coded" modules in cars, install access control systems, padlocks, install locks in office furniture. . . stuff like that.
Sales and marketing gurus: don't ask a locksmith to give you an "elevator pitch" unless it's a really long elevator ride.
• What's all this talk about bump keys? Can someone break into my house with them? What can I do to protect myself?
A bump key is a specially-cut key that can be used to manipulate pin-tumbler locks. They're not 100% successful, and do require a certain degree of aptitude to use, and are brand-specific. They've been around for years amongst locksmiths, but have recently been popularized through much publicity via the internet and news outlets.
Could someone use one to break into your house? Possibly, if they've got the proper key for the brand of locks on your house, and are proficient enough with them to be successful, and your locks are cooperative, and nobody catches them, etc., etc… For the record, we don't even use them, and we unlock stuff for a living. We make no argument to the contrary that the threat is real, we'd just like to inject a bit of common sense into it.
Bump-resistant or bump-proof locks are available, and modifications can be made to many existing lock cylinders to increase the resistance to bump keys, but as is often the case, protection is a matter of what you're willing to spend. At the top of the list, you could install Abloy deadbolts on all your exterior doors, coupled with some common-sense frame and door reinforcements, and sleep comfortably with the knowledge that your house is officially bump-proof. They're also nearly impossible to pick or manipulate, so if security is paramount, Abloy is our first choice. Unfortunately we don't stock or service Abloy locks (yet), but they're easy enough to find through various outlets on the internet, or if you're reading this from someplace other than east Tennessee, check with your local security professional. Not to say that Abloy is your only option, not by a long shot. Other manufacturers who offer bump-resistant locks: Medeco, Scorpion, Marks, ASSA, BiLock, Mul-T-Lock, and believe it or not, Kwikset's Smartkey series is bump-resistant, if not outright bump-proof. Sorry, we don't sell them (hard to compete with HD), but we'll gladly install yours if you've purchased them elsewhere.
Another very good piece of advice we've heard dispensed regarding protecting your home from bump keys: install auxiliary locks with no outside cylinder (barrel bolts, slide locks, etc) on any doors you don't normally enter through. It's simple enough to do, and we'd say is worth considering for any door that is out-of-sight from the rest of the neighborhood.
Best advice: security works best in layers. Motion lights, dense, thorny shrubbery around windows, a security system, and a good quality safe are all worthy of consideration when upgrading your home's security. A set of good, quality locks, properly installed, makes an excellent primary line of defense. A big, noisy dog and nosy neighbors don't hurt, either.
• What's the deal with your name, "Lock Medic"?
Our first service van was a retired (emphasis on 'tired') ambulance, and had evidently been adopted by an appliance repairman before we got our grubby little mitts on it. While sanding down years of old decals and lettering, Ben uncovered the name "Appliance Medic" . . . and in a staggering lack of creativity, decided to call the business "Lock Medic".
Second choice was "Atlas Lock & Key", but the cross/padlock logo proved easier to draw than a dude holding up the world.
• Are you a franchise?
Nope. Before the real-estate crash in 2008 we had a second store in Knoxville but we closed it shortly after and refocused our energy into our original Lenoir City store. Ben Turner, the store owner, is currently fantasizing about a career in aviation so he would entertain offers for the business and real estate if you're interested.
• Can you open anything?
Given enough time and coffee, sure. Anything the customer is authorized to have us do so . . . and is willing to pay for. One thing that we encourage all our customers to keep in mind is, we are a potential solution to your immediate problem of being locked out . . . we are generally not the only solution. If your vault time lock has been over wound by a few hours. Waiting for it to time out is probably a more realistic solution than having us drill it open.
• Can you replace any lost key? Can you copy any key I bring you?
Almost anything . . . the limiting factor is usually access to the right key blanks. Noteworthy exceptions: we can't copy or fit keys to proprietary or restricted key systems other than ones we sell, we can't program the electronic portion (the anti-theft "chip") of keys to some newer high-end European vehicles such as 98+ Mercedes Benz, 98+ Volvo, 2006+ BMW, and there are usually a few brand-new vehicles we might not be able to program yet. If we can't help you, we can usually point you in the direction of someone who can.
As the saying goes, there's more than one way to skin a cat. However, none of the ways of fitting a replacement key to a lock involves squirting any hardening 'goo' in the lock. We've really no idea where this rumor got started, but it most certainly wasn't a professional locksmith. We won't get into the physics behind why this won't work, but suffice to say, anything you could squirt into a lock that would harden will be staying there.
The only thing you'll ever see us squirt into a lock is lube or cleaner.
To answer the question more directly, our arsenal of methods of fitting replacement keys includes impressioning, disassembly & decoding, sight-reading, keyway specific pick & decode tools, and more direct methods such as by code. No single method works for all, so our technique is chosen by application.
• Why do you guys charge for opening cars when the police/firemen/random people with coat hangers do it for free?
Believe it or not, we get this question more often than you might think. Why do we charge? Because we like being able to eat, and pay the rent, and all that stuff . . . and also because it *costs* us money to be able to unlock things. A short list of the absolute minimum expenses that come in every month (whether or not we've had any billable services): fuel, vehicle payments, liability insurance, landline & cell phones, advertising, taxes (unemployment, payroll, property, personal property, city & county business license) professional licenses, continuing education, rent, and of course, the help likes to get paid, too. Now, if we were getting paid by the state (like police or fire depts.), we'd be happy to open your car for free.
Most police and fire departments only offer unlock service in life-or-death emergencies: i.e. only if someone is locked inside the car, such as an infant or someone either disabled or unconscious. Most departments that no longer offer non-emergency unlock service as a courtesy cite liability and the drain on their already overtaxed manpower reserves as reasons why. If your town does it, consider yourself lucky . . . and don't abuse the privilege.
Something to keep in mind: better than half of our customers have some form of roadside assistance, either through a roadside club such as AAA, or on their insurance policy, or in the case of a new vehicle, often from the automaker, or many cell phone carriers offer this on their plans. Most roadside assistance plans cover unlock service. Each policy is different, and some are reimbursement (meaning you pay us, then submit our invoice and whatever assorted paperwork your provider requests, then they pay you back), others use their own contracted service companies or will pay us (or another provider) with a credit card over the phone upon completion. Best to ask YOUR roadside provider how this works rather than us. Either way, we're happy to help as long as we're getting paid to do so.
• How do I get into your line of work? Where can I learn about locksmithing as a trade?
If apprenticeship isn't right for you, or just plain isn't an option, there are more than a few correspondence courses out there of varying degrees of credibility. Arguably one of the most well-known is a course offered by Foley-Belsaw. None of us here at Lock Medic (as of 2016) have ever even laid eyes on the course material, but several of our peers have learned through it and say it's a decent fundamentals course. . . but as anything else, a lot of it depends on the individual. Much like an apprenticeship, you'll get out of it what you put into it. There are a handful of specialized trade schools around the country that offer courses in locksmithing, and we're told that some high schools offer vo-tech classes, but none are available locally that we're aware of.
Last but certainly not least: ALOA, the most widely-recognized association for security professionals (the $5 term for "locksmith"), offers student memberships, and provides access to a wealth of information and fellowship. Several websites are devoted to the craft, one of our favorites being www.locksmithcommunity.com. And, of course, there's plenty of dead-tree format (a.k.a. "books") material out there, too. Take a look in your local library, or run through Amazon.com. TOOL (Tennessee Organization Of Locksmiths-www.tnlocksmiths.org ) offers classes in various (albeit usually intended for veterans of the trade) facets of the business from time to time.
As to getting into our line of work, if you're serious about locksmithing and wish to do it for yourself one day (i.e. start your own shop and put us out of business); we'd strongly suggest trying it first by working for an established shop. It's been our experience that enthusiasm does not always translate into aptitude, and just like most other small businesses, the failure rate vastly exceeds the success rate. Not saying you can't do it, just that we see lots of "like new, barely used" locksmith vans and tool sets for sale in the trade classifieds. More often than not, trade proficiency and business sense aren't found between the same pair of shoulders.
Probably not right now, but if you've had at least 5 years experience in commercial, residential, or automotive locksmithing, safe & vault service, or bring something else to the table, such as experience in metalworking, woodworking, construction, or automotive; or you're just an all-around mechanically, electronically, and socially adept person, you're always welcome to leave a resume.
• I see one of the requirements to earn my TN state locksmith license is 40 hours as an apprentice under a licensed locksmith. Can I work those 40 hours at Lock Medic?
We evaluate apprentices on a case-by-case basis. If you meet the state licensing requirements otherwise (qualifying education, no prior felony convictions, etc.) odds are good we'll be willing to take you on for your apprenticeship period as an unpaid intern. You will learn during the week, we don't abuse our interns by limiting their tasks to remedial stuff like stamping keys or sweeping the shop.
• If I hire you to rekey or make a key for my house, car, business, etc., how do I know you aren't going to keep a copy for yourself and come back later and steal my stuff?
First, we carry a bond that specifically protects our customers in such an event. Second, if we were the last people to touch your locks before your house gets burgled in a manner that suggests a key was used, you can bet that we'll be on top of the list of police interviews. Third, we wouldn't be in business for long if we had a reputation of breaking into our customer's establishments. Fourth, we don't like getting shot at.
• I hired you to rekey/make a key for [something] a while back, and now I've lost that key. Did you keep a file copy of my key so I can just come down and pick one up?
We never keep copies of our customer's keys because of the liability and logistical nightmare it would create. We will note your key code or bitting on your invoice if you specifically ask us to, but make no guarantee this information will be available later, so you shouldn't depend on us to do so. If we did note your key information on your invoice, the information, if available, will only be accessible during regular business hours at our storefront, not from our service trucks.
• What's a "Service Call", and why is it on my invoice?
The best way to describe it: The rental fee for one of our service trucks and a driver (one of our technicians) for the average amount of time it takes to get to a jobsite and back. This is typically charged once per invoice for field service. We didn't just pull a number out of a hat, it's actually based on what we calculated it costs to buy, outfit, maintain, insure, and operate a service truck and all the tools and machinery inside it on a yearly basis, plus the hourly rate of the tech driving it, divided by the average number of calls we run per year.


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Autosomal dominant GTP cyclohydrolase I deficiency (AD-GTPCHD) is a disease caused by dysfunction of GTP cyclohydrolase I, an enzyme that plays an important role in the synthesis of tetrahydrobiopterin, and, as a consequence, of dopamine. This condition is one of the six known causes of tetrahydrobiopterin deficiency and is the most frequently-reported cause of dopa-responsive dystonia.

Symptoms
In more than half the cases, the clinical picture is dominated by postural or action-induced dystonia of one or both lower limbs manifesting as gait difficulties. Dystonia gradually worsens during the day and becomes less pronounced after a period of rest. The fluctuating pattern is highly typical of this disease, especially in the first 30 years, after which this diurnal variation becomes less prominent.

The typical age at onset is during the first decade of life, although an onset in the second decade of life is also common, and in rare cases the disease may present itself in the first 12–18 months of life.

Diagnosis
Diagnosis is complicated because, unlike the majority of BH4 deficiencies, AD-GTPCHD does not present with hyperphenylalaninemia, and is therefore missed during newborn screening. Furthermore, unlike the majority of BH4 deficiencies, this condition does not have a specific pterin pattern. Thus, according to data gathered by the year 2021, the average delay of diagnosis ranged from 8 to 10 years.

According to a consensus guideline on BH4 deficiency published in 2020, if the presence of AD-GTPCHD is suspected, a genetic assessment should be carried out to look for mutations of the GTPCH1 gene. Genetic assessment requires specialized methods able to detect deletions, because in a significant number of patients with AD-GTPCHD no sequence alterations were found. Furthermore, cerebrospinal fluid analysis of biogenic amines and pterins (Figure 1) should be performed to gain additional clues.

If neither of the first-line tests described above (CSF, genetic tests) are available, a phenylalanine loading test could be performed, which could provide a clue by revealing an increased phenylalanine/tyrosine ratio.

In children whose symptoms are suggestive of dopa-responsive dystonia but for whom neither genetic nor biochemical assessment are available, L-dopa could be briefly prescribed as a trial to see if the patient's condition improves. In case of improvement, the patient would be suspected to have autosomal dominant GTP cyclohydrolase I deficiency, but would still have to undergo genetic and biochemical testing to distinguish their condition from other diseases.

Treatment
Patients are prescribed L-dopa in conjunction with a DC inhibitor such as carbidopa or benserazide. If symptoms persist, dopamine agonists such as pramipexole, bromocriptine, or cabergoline could be considered as a second line of treatment. Anticholinergic drugs or COMT inhibitors could be considered as a third line of treatment.

Epidemiology
As of 2020, there was a lack of precise data on the prevalence and incidence of the disease. One estimate, produced in 2017, puts the prevalence at 2.96 persons in a million people.

Alternative names
 Autosomal dominant Segawa syndrome (the autosomal recessive form of Segawa syndrome is caused by mutations in a different gene that encodes tyrosine hydroxylase)
 Dopa-responsive dystonia 5a
 Autosomal dominant DYT/PARK-GCH1 - designation in accordance with the Nomenclature of Genetic Movement Disorders maintained by the International Parkinson and Movement Disorder Society

See also
 Autosomal recessive GTP cyclohydrolase I deficiency -  condition associated with mutations of the same gene, GTPCH1

External links
Dystonia, DOPA-responsive, with or without hyperphenylalaninemia- description in the OMIM compendium.

References

Autosomal dominant disorders
Congenital disorders
Dystonia

redpajama_set_name: RedPajamaWikipedia


The lace that never needs tying. Allows the wearer to slip in and out of their shoes. Fits any shoe, only tightening and loosening, eliminating the dexterity and finger-strength challenges of making knots. With no pressure points, Curly Laces enable full natural movement and allow you to slip your shoes on safely and easily without having to tie your shoes, boots or sneakers.
couldn't wear proper shoes anymore until I got these. Hold shoe very securely.


text: Q: Проблема с nuget в Visual Studio 2012 Здраствуйте я недавно начал изучением С# установил визуал студио 2012 но каким то образом у меня нугет спрашиваеть обновление как можно решить этот проблему с сайта нугет не смогу установить обновленый нугет Спасибо заране


This notice informs all Rule Participants and interested parties (Consulted Persons) that AEMO has published a Procedure Change Proposal in respect of the revised Market Procedure: Undertaking the Long Term PASA and conducting a review of the planning criterion and is conducting a consultation process in respect of this proposal.
The matters are related to clause 4.5.14 of the WEM Rules which requires AEMO to document the process by which it conducts the Long Term PASA and the review required under clause 4.5.15 of the WEM Rules.
The submission period has now closed. No submissions were received.


Alain is working in collaboration with us and our clients to offer the best use in their kitchen space, along side our designs. Sunset Cuisine is Alain's personal website with an included blog, we've worked with him for many years and hope his insights are as helpful to you as they were to us.
Sunset Cuisine is a kitchen design and organization company founded by Chef Alain Buthion, who has spent thirty years perfecting his kraft at the popular La Baguette Bistro in Oklahoma City.
Always the perfectionist, Chef Alain developed his love for the culinary arts during his days assisting his father, a prominent Boucher in Grenoble, located in the South of France. Alain and his brother, Michel, came to the U.S. and began their careers in Oklahoma City, eventually opening LaBaguette Bistro at 7408 North May Avenue.
On numerous occasions, Alain has offered his cooking talents for charities and also assisted with food preparation in the homes of his patrons and friends. It was during this time that he recognized the need for a well-designed, carefully organized kitchen, including everything from the proper flow pattern during the preparation process to the appropriate cooking and eating utensils.
Thus, the birth of Sunset Cuisine, a hands-on service by a seasoned chef who wants you to enjoy your kitchen as much as he enjoys his.
"It's a badly needed service, whether you're re-designing or building a home or just wanting to be a better cook. The kitchen is the heart of the home in every respect."


If you have just started the game and would like a bit of friendly guidance, or have been playing for years but need a little bit of help on your game then why not contact our club coaches.
Club Dubbo have a group of coaches available at the club to help tend to your needs. Our coaches are all qualified and are well versed in the latest coaching techniques.


text:
De galapagoshaai (Carcharhinus galapagensis) is een haai uit de familie van de requiemhaaien. Hij komt voor rond eilanden in de oceanen en lijkt zich niet ver uit de buurt van die eilanden te verplaatsen.

Requiemhaaien
IUCN-status niet bedreigd


text:
1001 Floodlit Dreams
Isherwood Football Services
The problem with being George Best
January 23, 2020 January 30, 2020 Neil Fredrik Jensen
WE ALL wanted to be George Best. In the playground, on the football pitch, in the disco(!), in the boutique. He seemed to have everything that a virile male, circa 1967-72, needed to be a success in life: looks, women and outstanding ability.
But he was a flawed character, and there can be no other assessment as we now look back on his short and problematical life. The film, "Best", offers nothing new on this tortured individual and anyone watching it leaves the cinema saddened and perhaps a little angry.
It is terrible to see a life end prematurely, a football career shortened by self destruction and other people's lives wrecked by the behaviour of somebody who should still be with us today. But at the same time, this was a man who had many chances, many friends and many gifts. He wasn't a pop star, wasn't a person who could continue delivering greatness for decades because he was a sportsman. His window of opportunity was always going to be brief, if only he truly realised it.
Best said that he never had to work hard for anything and perhaps therein lies part of the problem. Less gifted men have made more of their careers and their more limited ability – Kevin Keegan is one that springs to mind. Maybe, just maybe, if Best had to work hard to become the football genius he so clearly was, he may have avoided some of the pitfalls that plagued him.
Because, when all is said and done, Best had the sort of "animal" talent that is seldom found in football. The likes of Messi and Ronaldo represent the pinnacle of the modern game, but their skills, their outstanding ability is a more refined and tactical skill-set. Best had this rawness that was both sinuous and sensual, twisting and turning, tricking and teasing. There was a poetic and balletic element that made football an art form to be admired and drooled over.
Best was not a "one trick pony", but he was a footballer. That was his trade and he was, at his peak, bettered by only a handful in the history of the game. In the current era, he would be a brand that would sustain him for decades. Sadly, the Best brand was destroyed as his life became a never-ending tale of alcohol, women, stop-gap employment and newspaper headlines.
When did it really start to go wrong? Best has said that after Manchester United won the European Cup, there was a sense of anti-climax at Old Trafford. He's not wrong, for the supporters felt that as much as anyone. United's fall from grace between 1968 and 1974 was down to a number of factors: Sir Matt Busby's retirement, poor managerial appointments, the decline of the holy trinity of Best – Charlton – Law and the club's inability to compete in the transfer market.
Best was only 22 when United won the European Cup. That team had an average age of 26, but included three who were over 30 (Brennan, Foulkes and Charlton) and along with Best, younger players like David Sadler (22), Brian Kidd (19) and John Aston (20). Denis Law, who was injured, was 28. With Charlton no longer as influential and Law hampered by fitness, the hub of the United team in the years that followed declined. It was invariably "give it George" and the pressure on him grew. Best shifted from being part of a trio to being the main hope for United and it was impossible for him to carry a diminishing force.
United dropped to mid-table in 1968-69 and Best scored a third of their 57 league goals. The next couple of seasons saw them become less influential and relevant as clubs like Leeds United and Arsenal set the narrative. It was clear that United's younger players were not made of the same stuff as Busby's title winners of 1967. Best, to quote somebody in the film, "started to make his own rules" and was constantly rubbing-up against the authorities. There were still flickers of genius, such as in 1970 when he hit six goals against Northampton in the FA Cup, but Best all too frequently looked like a man unhappy with himself and with his club. He made headlines either for going missing, being sent-off or for his womanising. Best became good copy for all the wrong reasons.
It has rarely been spoken of, but if Best was being driven to distraction because he was no longer in love with playing for United, would a transfer have solved some of his problems? Certainly United would have been able to cash-in on their prize asset and there would have been no shortage of buyers. The demon drink may still have been a problem, but perhaps a disciplinarian manager or a move to a club where he was among equals might have been more beneficial. It was not a move that any United manager would have relished for the public fall-out in Manchester would have been unbearable, but United ended up losing Best and getting nothing back.
It was in 1972-73 that it all came to a head, resulting in Best fleeing to Spain. On his 26th birthday, he announced his retirement from football, just a few months after United had said he would not play for them again. There was Best, dressed in reach attire, surrounded by his now familiar side-dishes of women and drink saying farewell to the sport that had made his name. At 26.
The question was, what would Best do now given that his only real talent was to play football. Retirement at 26 offered the potential of too much time at the bar.
So that's really the end of the story, but Best became a sort of fairground sideshow where he would play for whoever was willing to meet his demands: Dunstable, Stockport, Cork Celtic – you name it, he would arrive in a blaze of publicity, bring in the crowds for a short spell, miss training and then he would be gone. The United States provided a haven for a while, but the script was, by now, becoming very predictable and quite boring.
The last flicker of the light was in 1976 when he was signed by Fulham. There, alongside Rodney Marsh, he showed some glimpses of the old magic before disappearing in 1977-78. He also played for Hibernian in Scotland. Basically, the Best name was still a currency – and some people would take advantage of that, but the relationship with his employer never lasted too long.
It is hard not to feel sad about the Best story, but there is too much self-justification, too little accountability. The truth be known, Best appears an unremarkable character away from the football pitch, but then so often an artist can only express himself on canvas. Best's contemporaries always talk of him as a thoroughly nice guy, and there's something very endearing about him, but doesn't that just make this story all the more infuriating?
I'm glad I saw George Best in action, but I am equally glad I never met him in the pub.
Categories: playersTags: football history, George Best, Manchester United, top slot
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Game of the People is edited by Neil Jensen, an experienced corporate and football writer published in more than 40 publications worldwide.
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Dancing is an extraordinary method for investing energy, if your child is interested in dancing, its fitting to set aside some opportunity to locate an incredible school, something that'll guarantee that they can encourage their aptitudes. Before you invest hours driving around to various studios and glancing around, call a couple and ask a couple of key inquiries to ensure you agree to accept a program that is directly for you. Here are two or three things to ask so you can guarantee you've discovered the perfect spot for your kids to figure out how to dance.
Numerous studios have various classes that take into account offspring everything being equal. Subsequently, set aside some opportunity to learn concerning what the school brings to the table, implying that you're ready to know about what an instructor searches for in a child to guarantee that your youngster isn't forgotten. All the more along these lines, this will guarantee that your child can get the chance to learn with others, implying that they'll have the capacity to help each other in winding up better dancers. One of the greatest contrasts is that instructors who work with pre-school students will require almost unlimited measures of persistence since kids this little can be somewhat troublesome (yet fun!) to educate.
All the more in this way, before you pick a school, guarantee that it has options with regards to the sorts of dances and furthermore the classes, accordingly having the capacity to guarantee that in case you're a bustling guardian, your child will have something to keep them occupied. Instead of searching for a school which has one exercise seven days, search for one which will most likely show your tyke more moves, implying that the child will almost certainly adapt more than one dance. One advantage of finding a studio that has a wide range of classes is that you'll likely have the capacity to make up a class if your kid is debilitated on their standard class day. Through this, you get the opportunity to guarantee that your youngster can generally peruse more, this will guarantee that their development can be better since they know a portion of the methods for being involved.
In conclusion, get to ensure that you can find a school which will assist your child in learning which dance might suit them, at times, you'll find that its tough for a kid to decide as to the lessons they might like. These can incorporate starting the artful dance, tap, and jazz, just as hip jump, grown-up contemporary and even yoga! With this, you get to know as to some of the lessons that you need to register; besides, it'll ensure that you won't pay for a class that your child isn't interested in.


text:
Q: Shorter functions in ES2015? Consider the following code (taken from mdn):
var a = [
  "Hydrogen",
  "Helium",
  "Lithium",
  "Beryllium"
];

var a2 = a.map(function(s){ return s.length });

var a3 = a.map( s => s.length );

Is it possible to make it even shorter? E.g.:
var a4 = a.map( .length );

The above doesn't work (it results in a SyntaxError: Unexpected token .).
So is there any way to do that in ES2015?

A: Well, you can try to define a proxy object like this:
_ = new Proxy({}, {
    get: (t, name) => x => x[name]
});

and then
var a3 = a.map(_.length)

Whether this makes sense or not is another question.

A: Even shorter syntax would look like
   var a4 = a.map(({ length }) => length); // [8, 6, 7, 9]

where a4 element will be automatically invoked over length

A: You cannot do it like that, because it would be in conflict with the way property accessors are used.
From ECMAScript® 2015 Language Specification:

In specification text and algorithms, dot notation may be used to refer to a specific field of a Record value. For example, if R is the record shown in the previous paragraph then R.[[field2]] is shorthand for "the field of R named [[field2]]".

TL;DR The syntax is incorrect. You can't access a property of nothing without getting philosophical.


People frequently ask me for the contacts of web designers, photographers who do headshots, etc., so I've decided to compile a list of my resources.
John Marcom and Ari Solomon at Media BBQ do really beautiful work. Ari designed Craftsmanship Magazine. John designed the author website of Fred Vogelstein.
Alvaro Villenueva (alvarobookdesign (at) gmail (dot) com) specializes in book cover design. He also designed The Rumpus and MeghanWard.com.
Ilsa Brink specializes in author websites.
Bruno Trindade did Anna Alter's cool author websites.
Will Amato specializes in author websites.
Annie A. Chen did this wonderful site for my friend Molly Russell at 100% Organized.
Teresa Tauchi designed author websites for Laura Fraser and Yukari Kane. She can be contacted at ttauchi@boonin.net.
Bryan Cronk designed the author website of Ethel Rohan. He can be contacted at bryan.cronk@gmail.com.
Alta Peterson specializes in marketing, print design, and web design. She's great at customizing WordPress websites.
Sierra Fong also specializes in customizing WordPress blogs.
Lisa Gray is reasonably priced and designed Our Voices, Our Stories and The Dixwell Neighborhood Corporation sites. Contact her at ldgray2227@gmail.com.
For less expensive e-book formatters and book designers, you can subscribe to Smashwords' Mark's List by e-mailing list (@) smashwords (dot) com.
Laura Duldner takes fantastic daylight author photos for a resonable price. Contact her at lauraduldner@yahoo.com or 510.409.2046.
Chris Hardy did my photo over there on the right.
Elisa Urbon is a photographer from Madrid who shoots in her studio in Oakland. Contact her at elisaurbon@gmail.com for more information.
Angela Lang specializes in portraits, but does everything, too.
Sharon Donovan, formerly of Counterpoint Press, comes highly recommended. E-mail her at sharon (dot) donovan (at) comcast (dot) net.
Kathleen Matthews Schmidt of KMS PR is supposed to wonderful.
Leslie Rossman in Oakland also comes highly recommended. Contact her at lrossman (at) pacbell (dot) com.
Jonanna Widner charges $1/minute. Contact her at jonanna.vidner@gmail.com.
Michal Story is great. She can be contacted at michal@storytype.com.
I will update this page periodically with new resources.


text:
the alternative how to
guide for vagabonds, bohemians, and others
Tag: alternative
Music Monday: Latency
I can't get enough of Latency, the latest and greatest indie band to come out of Pennsylvania. Their new album I Should Have Met More People Tonight, was written, recorded, and produced by the two band members Sam Moran and Ryan Milloy in a basement, but it sounds anything but homemade. Fans of The Killers or pop-punk will enjoy this album, and it would be a perfect soundtrack for a first date or a laid back get together. My favorite track on the album is "Oh I Said It", a song about unrequited love. The album is free to download on Latency's bandcamp site, so give them a listen today.
Welcome to alternative how to!
If you've stumbled across this blog, chances are you're what people call "the creative type." Perhaps you travel across the country on trains, or you're busy creating sculptures out of your neighbors recycling bin. Maybe you draw pornographic anime on old vhs tapes, or make your own wine out of grape juice and yeast packets. Maybe you're a writer, an expert on surrealism, a fashion designer, a musician, or just a working stiff with a wild side. You might live in a busy city, a quiet beach, a suburb, in a house, a loft, an rv, or even a park. Regardless, you've just come across this blog because you are different. You have the insatiable desire to leave a mark on the world in your own unique way, the need to live differently and be inspiring. Welcome, readers, to alternative how to. A guide for anything and everything related to an alternative life, follow directions loosely and make changes as necessary. All advice given is merely a suggestion, intended to inspire and educate. Thank you for visiting alternative how to, and welcome.
– yourlovelymuse
Books: Making Stuff & Doing Things
tonight's inspiration: Oscar Wilde
How to kinda replace a typewriter ribbon
how to become an artist in 5 easy steps
Ms. Vee on how to become an artist in 5 e…
jilrob on how to become an artist in 5 e…
Laura on How to kinda replace a typewri…
Jeyna Grace on Welcome to alternative how…
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text:
1-deoxy-D-threo-hexo-2,5-diulose 6-phosphate + L-aspartate 4-semialdehyde = 2,3-dioxopropyl phosphate + 2-amino-2,3,7-trideoxy-D-lyxo-hept-6-ulosonate
UniProtKB help_outline 1,655 proteins
EC 2.2.1.10 2-amino-3,7-dideoxy-D-threo-hept-6-ulosonate synthase
Name help_outline 1-deoxy-D-threo-hexo-2,5-diulose 6-phosphate Identifier CHEBI:58861 Charge -2 Formula C6H9O8P InChIKeyhelp_outline XBUYIELOLLPBOC-PHDIDXHHSA-L SMILEShelp_outline CC(=O)[C@@H](O)[C@H](O)C(=O)COP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name help_outline L-aspartate 4-semialdehyde Identifier CHEBI:537519 Charge 0 Formula C4H7NO3 InChIKeyhelp_outline HOSWPDPVFBCLSY-VKHMYHEASA-N SMILEShelp_outline [H]C(=O)C[C@H]([NH3+])C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 13 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name help_outline 2,3-dioxopropyl phosphate Identifier CHEBI:58860 (Beilstein: 1874111) help_outline Charge -2 Formula C3H3O6P InChIKeyhelp_outline NZAAQWRNVFEKME-UHFFFAOYSA-L SMILEShelp_outline [H]C(=O)C(=O)COP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name help_outline 2-amino-2,3,7-trideoxy-D-lyxo-hept-6-ulosonate Identifier CHEBI:58859 Charge 0 Formula C7H13NO5 InChIKeyhelp_outline IFMHGOADXGYWMO-KVQBGUIXSA-N SMILEShelp_outline CC(=O)[C@@H](O)[C@H](O)C[C@H]([NH3+])C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
1,655 proteins
RXN-10031
L-aspartate semialdehyde and a 6-deoxy-5-ketohexose 1-phosphate are the precursors to the aromatic amino acids in Methanocaldococcus jannaschii.
White R.H.
No orthologs are present in the genomes of the archaea encoding genes for the first two steps in the biosynthesis of the aromatic amino acids leading to 3-dehydroquinate (DHQ). The absence of these genes prompted me to examine the nature of the reactions involved in the archaeal pathway leading to ... >> More
No orthologs are present in the genomes of the archaea encoding genes for the first two steps in the biosynthesis of the aromatic amino acids leading to 3-dehydroquinate (DHQ). The absence of these genes prompted me to examine the nature of the reactions involved in the archaeal pathway leading to DHQ in Methanocaldococcus jannaschii. Here I report that 6-deoxy-5-ketofructose 1-phosphate and l-aspartate semialdehyde are precursors to DHQ. The sugar, which is derived from glucose 6-P, supplies a "hydroxyacetone" fragment, which, via a transaldolase reaction, undergoes an aldol condensation with the l-aspartate semialdehyde to form 2-amino-3,7-dideoxy-D-threo-hept-6-ulosonic acid. Despite the fact that both hydroxyacetone and hydroxyacetone-P were measured in the cell extracts and confirmed to arise from glucose 6-P, neither compound was found to serve as a precursor to DHQ. This amino sugar then undergoes a NAD dependent oxidative deamination to produce 3,7-dideoxy-d-threo-hept-2,6-diulosonic acid which cyclizes to 3-dehydroquinate. The protein product of the M. jannaschii MJ0400 gene catalyzes the transaldolase reaction and the protein product of the MJ1249 gene catalyzes the oxidative deamination and the cyclization reactions. The DHQ is readily converted into dehydroshikimate and shikimate in M. jannaschii cell extracts, consistent with the remaining steps and genes in the pathway being the same as in the established shikimate pathway. << Less
Biochemistry 43:7618-7627(2004) [PubMed] [EuropePMC]
Structure of 2-amino-3,7-dideoxy-D-threo-hept-6-ulosonic acid synthase, a catalyst in the archaeal pathway for the biosynthesis of aromatic amino acids.
Morar M., White R.H., Ealick S.E.
Genes responsible for the generation of 3-dehydroquinate (DHQ), an early metabolite in the established shikimic pathway of aromatic amino acid biosynthesis, are absent in most euryarchaeotes. Alternative gene products, Mj0400 and Mj1249, have been identified in Methanocaldococcus jannaschii as the ... >> More
Genes responsible for the generation of 3-dehydroquinate (DHQ), an early metabolite in the established shikimic pathway of aromatic amino acid biosynthesis, are absent in most euryarchaeotes. Alternative gene products, Mj0400 and Mj1249, have been identified in Methanocaldococcus jannaschii as the enzymes involved in the synthesis of DHQ. 2-Amino-3,7-dideoxy-d-threo-hept-6-ulosonic acid (ADH) synthase, the product of the Mj0400 gene, catalyzes a transaldol reaction between 6-deoxy-5-ketofructose 1-phosphate and l-aspartate semialdehyde to yield ADH. Dehydroquinate synthase II, the product of the Mj1249 gene, then catalyzes deamination and cyclization of ADH, resulting in DHQ, which is fed into the canonical pathway. Three crystal structures of ADH synthase were determined in this work: a complex with a substrate analogue, fructose 1,6-bisphosphate, a complex with dihydroxyacetone phosphate (DHAP), thought to be a product of fructose 1-phosphate cleavage, and a native structure containing copurified ligands, modeled as DHAP and glycerol. On the basis of the structural analysis and comparison of the enzyme with related aldolases, ADH synthase is classified as a new member of the class I aldolase superfamily. The description of the active site allows for the identification and characterization of possible catalytic residues, Lys184, which is responsible for formation of the Schiff base intermediate, and Asp33 and Tyr153, which are candidates for the general acid/base catalysis. << Less
Biochemistry 46:10562-10571(2007) [PubMed] [EuropePMC]
MJ0400 from Methanocaldococcus jannaschii exhibits fructose-1,6-bisphosphate aldolase activity.
Samland A.K., Wang M., Sprenger G.A.
The central carbon metabolism is well investigated in bacteria, but this is not the case for archaea. MJ0400-His(6) from Methanocaldococcus jannaschii catalyzes the cleavage of fructose-1,6-bisphosphate (FBP) to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate with a V(max) of 33 mU mg(-1 ... >> More
The central carbon metabolism is well investigated in bacteria, but this is not the case for archaea. MJ0400-His(6) from Methanocaldococcus jannaschii catalyzes the cleavage of fructose-1,6-bisphosphate (FBP) to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate with a V(max) of 33 mU mg(-1) and a K(m) of 430 microM at 50 degrees C. MJ0400-His(6) is inhibited competitively by erythrose-4-phosphate with a K(i) of 380 microM and displays heat stability with a half-life of c. 1 h at 100 degrees C. Hence, MJ0400 is the second gene encoding for an FBP aldolase in M. jannaschii. Previously, MJ0400 was shown to act as an 2-amino-3,7-dideoxy-D-threo-hept-6-ulosonic acid synthase. This indicates that MJ0400 is involved in both the carbon metabolism and the shikimate pathway in M. jannaschii. << Less
FEMS Microbiol. Lett. 281:36-41(2008) [PubMed] [EuropePMC]