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Researchers Find Roots of Neuropsychiatric Diseases in Developing Brain
Neuroscience News December 14, 2018
Artificial IntelligenceAutismdeep learningFeaturedGeneticsmachine learningNeuroscienceneurotechOpen Neuroscience ArticlesPsychology9 min read
Summary: Researchers found differences in cells types between 16 regions of the brain during development may be key in determining whether genetic risks translate into disorders like ASD, schizophrenia or bipolar disorder.
Source: Yale.
The most comprehensive genomic analysis of the human brain ever undertaken has revealed new insights into the changes it undergoes through development, how it varies among individuals, and the roots of neuropsychiatric illnesses such as autism spectrum disorders and schizophrenia.
The multi-institutional analysis of almost 2,000 brains integrates the complex choreography of brain development and function and was published Dec. 14 in 11 studies appearing in a special edition of the journal Science and two sister publications.
Four of the major studies were spearheaded by researchers from a variety of disciplines at Yale University, which is leading an ambitious initiative wedding neuroscience and data science. The Yale-led research papers illustrate the host of new tools scientists at 15 institutions are employing to find the molecular basis of neuropsychiatric diseases — the goal of the PsychENCODE Consortium founded in 2015 by the National Institutes of Health.
The sheer scope of data gathered on the activity of single genes and regulatory networks that control them over the course of development allowed data scientists to evaluate the risk of diseases such as schizophrenia and bipolar disorder with up to six times more accuracy than by traditional analysis of known genetic risk variants, according to research headed by Mark Gerstein, Yale's Albert L Williams Professor of Biomedical Informatics; professor of molecular biophysics & biochemistry, computer science, and statistics & data science; and co-corresponding author of two of the major Science papers.
Researchers also found that these risk variants can influence the function of genes very early in development and through a lifetime, but have a greater chance of manifesting themselves as symptoms as they form distinct groupings or modules during different stages of development.
Findings of the lab of Yale's Nenad Sestan, explain why the risk of developing many neuropsychiatric illnesses such as autism and schizophrenia can vary over time. Sestan is professor of neuroscience, comparative medicine, genetics, and psychiatry, and corresponding or co-corresponding author of two of the major Science papers,
Healthy brain development and neurological function rely on precise regulation of gene expression, which varies substantially by region and cell type in the human brain. Sestan's lab found that differences in cell types between 16 regions of the human brain during development may be a key factor in determining factor whether genetic risk translates into a neuropsychiatric disorder.
Healthy brain development and neurological function rely on precise regulation of gene expression, which varies substantially by region and cell type in the human brain. NeuroscienceNews.com image is in the public domain.
They also found that the greatest variation in cell types and gene expression activity happen early in prenatal development, decrease late in pregnancy and in early childhood, and begin to increase again in early adolescence. This "cup-like" pattern of development is shared by rhesus macaque monkeys, a primate species closely related to humans. Moreover, the same study led by Sestan' s lab also identified features of brain development that differ between humans and macaque, including unique gene expression signatures of human late childhood.
It is during these periods of greatest developmental change that risk susceptibility genes tend to form distinct networks, or modules, in certain brain areas, researchers found. The modules linked to autism tend to form early in development and those linked to schizophrenia — as well as IQ and neuroticism — tend to form later in life. This may explain why neuropsychiatric disorders like autism appear early childhood and schizophrenia appear early adulthood, say the researchers The analysis also shows how genes linked to illness are also expressed in specific cell types, which helps determine the scope and effect of specific disease-associated genetic variations.
The molecular events that lead to neuropsychiatric disorders can precede symptoms by months or even years, researchers report.
"Risk factors for disease are always present, but they are not equally manifested across time and space," Sestan said.
The changes to the brain were tracked in a living system used by the lab of Flora Vaccarino, Yale's Harris Professor in the Child Study Center and professor in the Department of Neuroscience, and co-corresponding author of one of the major Science papers. Researchers coaxed human stem cells derived from the tissue of individuals to develop into brain organoids, collection of neural cell types that mimic in cell culture the early stage development of the human brain. The organoids recapitulated the first trimester human brain development, when neural stem cells start differentiating into the multitude of neuron types that make up the brain. This system allowed researchers to identify and follow over time the gene regulatory networks active in early cortical development, a period that carries considerable genetic and environmental risk for developmental disorders such as autism. Known autism risk genes — as well as regulatory elements that control their activity — are highly expressed in the organoids at this stage, they found. The genetic risk variants previously linked to autism and that disrupt regulatory elements were active in the organoids, they report.
"This model can potentially reveal how those genetic risk variants lead to disease," Vaccarino said.
The massive amounts of information collected by PsychENCODE researchers have been organized in an accessible data "atlas." This allows data scientists to employ deep-learning analysis or a machine-learning approach loosely inspired by human cognition to find clues to combat the progression of neuropsychiatric disorders in individuals. For example, scientists can now integrate information from single-cell sequencing with more traditional genomics measurements of "bulk" tissue samples and capture the differences among a large population of people at different stages of development. This approach allowed Gerstein's lab to show that much of the differences in gene expression between individuals were due to changing proportions of basic cell types, such as excitatory neurons
Funding: National Institutes of Health funded this study.
Source: Bill Hathaway – Yale
Original Research: Abstract for "Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder" by Michael J. Gandal, Pan Zhang, Evi Hadjimichael, Rebecca L. Walker, Chao Chen, Shuang Liu, Hyejung Won, Harm van Bake, Merina Varghese, Yongjun Wang, Annie W. Shieh, Jillian Haney, Sepideh Parhami, Judson Belmont, Minsoo Kim, Patricia Moran Losada, Zenab Khan, Justyna Mleczko, Yan Xia, Rujia Dai, Daifeng Wang, Yucheng T. Yang, Min Xu, Kenneth Fish, Patrick R. Hof, Jonathan Warrell, Dominic Fitzgerald, Kevin White, Andrew E. Jaffe, PsychENCODE Consortium, Mette A. Peters, Mark Gerstein, Chunyu Liu, Lilia M. Iakoucheva, Dalila Pinto, Daniel H. Geschwind in Science. Published December 14 2018.
doi:10.1126/science.aat8127
Yale"Researchers Find Roots of Neuropsychiatric Diseases in Developing Brain." NeuroscienceNews. NeuroscienceNews, 14 December 2018.
<http://neurosciencenews.com/brain-development-asd-schizophrenia-10345/>.
Yale(2018, December 14). Researchers Find Roots of Neuropsychiatric Diseases in Developing Brain. NeuroscienceNews. Retrieved December 14, 2018 from http://neurosciencenews.com/brain-development-asd-schizophrenia-10345/
Yale"Researchers Find Roots of Neuropsychiatric Diseases in Developing Brain." http://neurosciencenews.com/brain-development-asd-schizophrenia-10345/ (accessed December 14, 2018).
Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder
Our understanding of the pathophysiology of psychiatric disorders, including autism spectrum disorder (ASD), schizophrenia (SCZ), and bipolar disorder (BD), lags behind other fields of medicine. The diagnosis and study of these disorders currently depend on behavioral, symptomatic characterization. Defining genetic contributions to disease risk allows for biological, mechanistic understanding but is challenged by genetic complexity, polygenicity, and the lack of a cohesive neurobiological model to interpret findings.
The transcriptome represents a quantitative phenotype that provides biological context for understanding the molecular pathways disrupted in major psychiatric disorders. RNA sequencing (RNA-seq) in a large cohort of cases and controls can advance our knowledge of the biology disrupted in each disorder and provide a foundational resource for integration with genomic and genetic data.
Analysis across multiple levels of transcriptomic organization—gene expression, local splicing, transcript isoform expression, and coexpression networks for both protein-coding and noncoding genes—provides an in-depth view of ASD, SCZ, and BD molecular pathology. More than 25% of the transcriptome exhibits differential splicing or expression in at least one disorder, including hundreds of noncoding RNAs (ncRNAs), most of which have unexplored functions but collectively exhibit patterns of selective constraint. Changes at the isoform level, as opposed to the gene level, show the largest effect sizes and genetic enrichment and the greatest disease specificity. We identified coexpression modules associated with each disorder, many with enrichment for cell type–specific markers, and several modules significantly dysregulated across all three disorders. These enabled parsing of down-regulated neuronal and synaptic components into a variety of cell type– and disease-specific signals, including multiple excitatory neuron and distinct interneuron modules with differential patterns of disease association, as well as common and rare genetic risk variant enrichment. The glial-immune signal demonstrates shared disruption of the blood-brain barrier and up-regulation of NFkB-associated genes, as well as disease-specific alterations in microglial-, astrocyte-, and interferon-response modules. A coexpression module associated with psychiatric medication exposure in SCZ and BD was enriched for activity-dependent immediate early gene pathways. To identify causal drivers, we integrated polygenic risk scores and performed a transcriptome-wide association study and summary-data–based Mendelian randomization. Candidate risk genes—5 in ASD, 11 in BD, and 64 in SCZ, including shared genes between SCZ and BD—are supported by multiple methods. These analyses begin to define a mechanistic basis for the composite activity of genetic risk variants.
Integration of RNA-seq and genetic data from ASD, SCZ, and BD provides a quantitative, genome-wide resource for mechanistic insight and therapeutic development at Resource.PsychENCODE.org. These data inform the molecular pathways and cell types involved, emphasizing the importance of splicing and isoform-level gene regulatory mechanisms in defining cell type and disease specificity, and, when integrated with genome-wide association studies, permit the discovery of candidate risk genes.
AIartificial intelligenceASDAustismautism spectrum disorderbipolar disorderbrain developmentdeep learningdepressiondevelopmental neuroscienceGeneticsmachine learningneurodevelopmentNeuroscienceneurotechpsychiatryPsychologyYale
December 15, 2018 Greeley Miklashek, MD
Nice story but I like mine better: neurodevelopmental spectrum disorders are caused not by "bad genes (since we all have essentially the same geneset)" but rather by the INHIBITION of gene expression due to elevated stress hormone cortisol levels in early brain development. Cortisol is known to cross the BB barrier in early fetal brain development and the different disordered outcomes depend on the timing of high stress exposure in the womb. So, the problem is in the lack of normal development in whatever neuronal nucleus that would have otherwise been developing at that moment in development. We have become slaves to our technology in neuroscience and stopped using our brains, if any out there are actually still functional. Stress R Us


Caught and released this 11 lbs. buck on a Fay's Janis Jig this morning, Sunday, February 10.
Caught and released this 6lb male on Sunday 2/10 on a black and white jig tipped with maggots.
My son and I went to Wallace Lake today (Saturday) to try and catch a trout or two. We weren't able to land a keeper; but my son did catch 3 round Gobies, near the life guard chair. I'll keep them in a bag frozen; if needed.


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Trump's revival of claim of voting fraud in N.H. alarms some state Republicans
Officials have said repeatedly that there is no evidence to support the president's claim that out-of-state voters cast ballots in New Hampshire.
By Amy Gardner
Donald Trump speaks at a campaign rally on Aug. 15 in Manchester, N.H. Associated Press
It was one of the first claims President-elect Donald Trump made about voter fraud in the wake of his 2016 victory: that his whisker-thin loss in New Hampshire was propelled by thousands of illegal ballots cast by out-of-state voters.
Trump's revival of that false assertion as he ramps up his reelection campaign is now alarming some New Hampshire Republicans, who fear that the president's allegations could undermine confidence in next year's election.
"People hold riots after their favorite football team loses the Super Bowl," said Fergus Cullen, a former New Hampshire GOP chairman and Trump critic. "There's just no telling what people will do when they're incited to it. We've never been in a situation like this, where there's so much dry kindling across the landscape and we've got someone all too willing to light the match."
After losing the popular vote in 2016 by nearly 3 million votes, Trump immediately raised the specter of voting fraud. He alleged without evidence that millions of people voted illegally in California, Virginia and New Hampshire – three states where he lost to Democratic rival Hillary Clinton. He claimed he would have won the overall popular vote "if you deduct the millions of people who voted illegally."
"Why isn't the media reporting on this?" Trump asked in a tweet on Nov. 27, 2016.
Shortly after his inauguration, the president announced plans for a commission to investigate alleged voter fraud, which ended up disbanding barely a year later with no findings.
With his reelection campaign now underway, Trump has returned to the topic.
"New Hampshire should have been won last time," the president told reporters on Aug. 15, en route to a campaign rally in Manchester, "except we had a lot of people come in at the least moment, which was a rather strange situation. Thousands and thousands of people coming in from locations unknown. But I knew where their location was."
New Hampshire officials have said repeatedly that there is no evidence to support the president's claim. A review by the New Hampshire secretary of state and the attorney general's office of all 6,033 voters who cast ballots in 2016 without proof of a New Hampshire address verified the residency of the vast majority of them and led to a handful of inquiries into possible improper voting.
"It is just not accurate" that thousands of out-of-staters voted illegally in New Hampshire, Secretary of State Bill Gardner said in an interview.
Trump's campaign spokesman, Tim Murtaugh, did not respond to a request for comment.
Some believe the president's accusations pose a particular threat to New Hampshire's jealously guarded spot at the start of the presidential primary schedule if he undermines national confidence in the integrity of state elections and prompts scrutiny of whether that role should continue. In turn, the retail politicking the small state demands could give way to expensive campaign advertising in a bigger state.
"That could ultimately cost our place in the process," said Josh McElveen, a New Hampshire consultant for both parties who is currently advising Don Bolduc, a Republican candidate for U.S. Senate. "I think that would be bad for New Hampshire, and I think it would be bad for the country. It would only make money more influential."
New Hampshire allows same-day registration, meaning a voter can walk into a polling location on Election Day and register and cast their ballot all at once.
Thousands of voters show up at the polls without the proper proof that they are eligible to vote. In those cases, voters are required to sign an affidavit attesting to their eligibility.
Over the years, state elections officials have fielded claims that out-of-state voters are taking advantage of same-day registration on Election Day.
Randal Heller, a political activist from Barrington, New Hampshire, is an independent who voted for Trump in 2016. He said he overheard college students waiting for a polling location to open and worrying that their photograph might be taken. Heller said he shared his concerns with state Republicans.
"It raises suspicion that perhaps they are not entitled to be voting in the state of New Hampshire," said Heller, who is 66 and a retired Naval officer.
But officials have not found evidence to support such allegations.
Gardner – a Democrat who was a member of Trump's now-disbanded voting fraud commission – said he has received calls from voters reporting dozens of people pouring out of buses with Massachusetts tags and filing into voting locations. He said he has never found evidence of wide-scale illegal voting; one time, he learned after following up on such a tip that the bus was filled with political science students from Wellesley College who had driven up with their professor to observe New Hampshire's first-in-the-nation primaries.
"You've got thousands of people at polling places with phones, with cameras, and nobody has a videotape," said Cullen, the former state GOP chair. "I'm reminded how there used to be sightings of Bigfoot and aliens all the time."
Kathy Sullivan, a former state Democratic Party chair, said the accusations first surfaced when Democrats started winning statewide races regularly.
"It was as if New Hampshire Republicans couldn't believe that New Hampshire could vote for Democrats," Sullivan said. "So they started claiming that we were bussing people in from Massachusetts, which of course is a made-up thing."
Gardner's office, along with the attorney general's office, reviewed all the voter affidavits signed during the 2016 election. State officials confirmed the eligibility of the vast majority, pursing only four cases of potential wrongful voting, according to their report.
One resulted in a fine. Three were dismissed after investigators determined the voters had attempted to register during hospital stays, according the attorney general's office.
Using a multistate database, state officials also scrutinized potential instances of duplicate voting in New Hampshire and elsewhere, resulting in five prosecutions. One resulted in a guilty plea for fraud, while four cases are ongoing, the attorney general's office said.
State GOP leaders have stopped short of endorsing Trump's claims, but they cited the potential for out-of-state voting when they passed a law last year requiring voters to comply with strict residency requirements such as getting a New Hampshire driver's license and vehicle registration. Critics have argued in a pending lawsuit that the law unfairly targets college students with the equivalent of a poll tax.
Republican supporters said that until the measure passed, college students from out-of-state were allowed to vote in New Hampshire without establishing the state as their legal residence.
"Look, they didn't steal it because the laws allowed them to," Gov. Chris Sununu said in an interview on the Howie Carr Show in January, referring to the 2016 victories of Clinton and Democratic Sen. Maggie Hassan in the state. "We had these very gray, amorphous laws that allowed it to happen. Did they do anything illegal? No, I don't think they did anything illegal. I think we just had these loopholes that existed, and they exploited it."
Sununu added that if the state's college students hadn't been allowed to participate in the election, Trump and then-Sen. Kelly Ayotte would have won "by a landslide. Yeah. It's not even close. Not even close."
He said the new law "fixed" the problem – a statement that Democrats have seized upon as evidence that the law's real intention is to discourage New Hampshire college students from voting.
Some Republicans who find Trump's rhetoric problematic nevertheless defend the new law.
"I don't want to limit anybody's right to vote, but I also think that it's a legitimate thing to protect, to ensure that only those people who do have a legal right to vote are the ones voting," said Jennifer Horn, a former state GOP chair and frequent Trump critic.
But she added: "We've turned something that should be a basic American ideal into a partisan issue, and I think that's a shame. And I think this president has figured out very quickly how to take advantage of that."
In the radio interview, Sununu, an avid Trump fan, indicated the president is fixated on the issue of voter fraud in New Hampshire. "Oh, trust me, he's asked me every time" they speak, the governor said.
Trump's landslide victory in the New Hampshire primary in 2016, which boosted his campaign after he had lost the Iowa caucuses to Sen. Ted Cruz (R-Tex.), has shaped his complicated relationship with the state.
After Clinton won the state in the general election by 2,736 votes – less than one-half of a percentage point – Trump immediately questioned the results.
Corey Lewandowski, Trump's former 2016 campaign manager, who is considering a bid for the U.S. Senate in New Hampshire, said the new residency law will make a difference for Trump as well as the GOP Senate nominee next year.
"You can't just walk into the state of New Hampshire anymore with a Massachusetts, Vermont or Maine ID and say, 'I want to vote,' " Lewandowski said in an interview. "It was ripe for voter fraud, and the legislature addressed that."
Asked if he was aware of any instances of such fraud, he said: 'If one person votes illegally in the state, it's one person too many."
'Fox isn't working for us anymore,' Trump tweets
Conservative group pushing Mills to veto bill for ranked-choice primary
Lingering power outages reported following Saturday storm
Maine Capitol quiet late Sunday morning amid protest concerns

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Home Headlines & Top Stories Breakthrough expected for joint sewage treatment plant | THE DAILY HERALD
Headlines & Top Stories
Breakthrough expected for joint sewage treatment plant | THE DAILY HERALD
THE HAGUE–Dutch State Secretary of Home Affairs and Kingdom Relations Raymond Knops announced on Tuesday that he expects a breakthrough in the joint sewage treatment plant project for Dutch St. Maarten and French St. Martin.
Knops made the announcement during a general debate in the Second Chamber of the Dutch Parliament on Tuesday evening about the effects of the crisis in Venezuela on Curaçao, Aruba and Bonaire. He mentioned the cooperation of the Dutch government with St. Maarten during that debate.
"It seems that there will finally be a breakthrough in the joint wastewater management project for St. Maarten and St. Martin," he stated. He did not provide details on what that breakthrough would be, but he did say that the project was on the agenda of a meeting with the World Bank in Washington DC later this week.
Knops said he would travel to Washington today, Wednesday, for a meeting with the World Bank. No details on that meeting were available on Tuesday. The World Bank manages the St. Maarten Recovery Trust Fund on behalf of the Dutch government.
Knops said that both the Netherlands and France were committed to working together in the interest of St. Maarten and St. Martin.
The project for a joint sewage treatment plant servicing the communities of Marigot, Cole Bay and Simpson Bay has been on the books since 2015. The need for this project was emphasised by the then St. Maarten government headed by Prime Minister Marcel Gumbs.
Territorial Council President Aline Hanson announced in January 2016 the approval by the European Commission of the trans-border cooperation programme with St. Maarten. At the time, the joint Cole Bay sewage treatment plant was to be the first of the projects to start.
Then St. Maarten Prime Minister William Marlin and a delegation of government officials met in August 2016 with then Préfète Déléguée Anne Laubies, representatives of the Collectivité of St. Martin and Louis Fleming to discuss the Territorial Cooperation Programme for St. Martin/St. Maarten 2014-2020. The programme focused on environment and safety.
Because there were some concerns from residents about the proposed locations, it was decided to have a study carried out to have yet another look at other possible locations for the joint wastewater treatment plant. No mutual agreement was reached, and the joint sewage project for Cole Bay was shelved, even though the European Union (EU) had made financial means available for the project.
The project is essential to prevent more pollution of the area and to keep dirty water from flowing through the area, much of it ending up in Simpson Bay Lagoon. Sewage treatment is listed as one of the areas of importance in the St. Maarten National Recovery and Resilience Plan (NRRP), along with housing, debris and solid waste management.
Source: The Daily Herald https://www.thedailyherald.sx/islands/87022-breakthrough-expected-for-joint-sewage-treatment-plant
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Welcome to the eighth Sneem International Storytelling and Folklore Festival. This year's storytellers are Kate Corkery from Cork and London, Liz Weir from Northern Ireland, Batt Burns from Kerry and singer Jimmy Crowley from Cork, with guest tellers Paddy Regan (Cork), Eamon Crowley and Vincent Hyland (Kerry).
This year we have two plays on Saturday: the first is written and performed by Kate Corkery "The Sweetshop on the Shore".
Our feature play is developed through the Show in a Bag programme, supported by Fishamble, The Irish Theatre Institute and The Dublin Fringe Festival. "Brendan Galileo for Europe" is written and performed by Fionn Foley.
Patrons can look forward to children's performances, adult story swaps, pub trail, storytelling in the barn, and The South Kerry Rosen Choir will be back to entertain you in the Church. The Young Tellers will be enthralling you with their stories, John Sheehan from UCC makes a return visit, as does our popular lunchtime theatre from Sneem Dramsoc.
We have something for all ages, for visitors and locals alike. We hope you enjoy our Festival in our colourful village. We're here to answer any questions you might have. Get in touch using the contact form below.
Sneem, Co. Kerry, Ireland
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Roaming Robots presented a corporate show on December 8th at the Williams F1 HQ and Conference Centre Christmas party, and an educational workshop on December 10th at St. Albans School.
● Beetleweights — 1st: "Pure Dead Brilliant," Team Rolling Thunder.
● Hobbyweight — 1st: Apollyon," Team Near Choas Robotics; 2nd: "Cheep Shot 3.0," Team Rolling Thunder.
● Featherweight Tag Team Competition — 1st: "Beauty" (FP flipper), "Rip" (LP flipper); 2nd: "Little Hitter" (CO2 powered Axe), "G3" (FP Flipper).
Central Illinois Bot Brawl 2008 will be presented by Central Illinois Robotics Club in Peoria, IL on 3/29/2008. Go to http://circ. mtco.com for more details.
Categories will be: RC Combat (1 lb Ants only), Autonomous Sumo ( 3 kg, 500 g, LEGO), Line Following, Line Maze. Entry fee is $7 per entry if you pre-register, $10 per entry for walk-ins. Free admission for spectators.
BotsIQ will hold a Regional Competition on 3/28-29/2008 in Pittsburg, PA. Go to www.bots iq.org for more details.
Roaming Robots will hold an event on 4/6/2008 at the Fenton Manor Sports Complex, City Road, Fenton, Stoke on Trent, ST4 2RR, UK. Go to www.roaming robots.co.uk for more details.
Robots Live will hold an event 4/12-13/2008 at Olympos Burgess Hill, The Triangle, Triangle Way, Burgess Hill, West Sussex, RH15 8WA UK. Go to www.robots live.co.uk for more details.
Seattle Bot Battles 2008 will be presented by Western Allied Robotics in Seattle, WA on 4/12/2008 at the Seattle Center's "Center House." Go to www.westernalliedrobotics.com for more details.
Round Robin (RFL Rules). No ICE or open flames. Entry Fee: $25 for first 3 lb or 1 lb robot. Additional robots are half price. Special entry fee considerations for builders who are under 18. Arena: 8 x 8.
Rotunda Rumble will be presented by Synergy Robotics Entertainment in Minneapolis, MN, on 4/25-27/2008. Go to www.kickbot.org for more details.
Perform in front of thousands of screaming fans at the largest tourism destination in the world. The Mall of America, Synergy Robotics Entertainment, and the CRCA are proud to announce "Rotunda Rumble." Rotunda Rumble will feature multiple weight classes in both the STUDENT and PROFESSIONAL leagues. The main event will run 150 gram, Ant (1 lb), Beetle ( 3 lb), Hobbyweight ( 12 lb), 15lb, and Featherweight ( 30 lb) classes.
Prizes: Student 15 lb Class; $2,500 in merchandise for 1st Place, Trophies to 1st, 2nd, and 3rd Place. Professional 12 lb and 30 lb Class; $500 to 1st Place, Trophies to 1st, 2nd, and 3rd Place.
BotsIQ: The Competition 2008 will be presented by BotsIQ in Miami Beach, FL on 4/30/2008-5/4/2008. Go to www.botsiq.org for more details.


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HomeSurgery and Medical Guides
Master Henry - January 30, 2023
CT scan (Computed Tomography Scan) is an imaging technique that uses several rotating X-ray beams to obtain images of internal organs. Compared to X-ray...
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An exciting opportunity in the property sector to work with a national fashion retailer's leasing department. The leasing coordinator will analyse, negotiate and finalise lease renewals with various landlords.
The environment is dynamic and provides an abundance of learning opportunities.
Obtaining, preparing and sending of offers and leases for new and existing stores, including the drafting of special conditions where needed.


I visited the Eden Day Spa in Lower Manhattan with my friend to celebrate her birthday. Although it's not the biggest place, the atmosphere was beautiful, relaxing and everything we needed to rejuvenate.
We chose the 60 minute massages since they were running a special for the week and definitely got our money's worth. In addition to the snacks, there was a complimentary lunch provided. I chose the pasta with shrimp, chicken and mushrooms and it was delicious.
After the massages and lunch, we were exhausted so we steamed in the sauna for a few minutes then left. I would recommend this spa if you're in NYC on a budget. I'll know I'll definitely be back to see Sam for another amazing massage.


You are visiting the placeholder page for Dennis Smith. This page is here because someone used our placeholder utility to look for Dennis Smith. We created this page automatically in hopes Dennis Smith would find it. If you are not Dennis Smith, but are an alumni of North East High School North East, MD, register on this site for free now.


Faith Grace kept her mouth close. Alam niyang tinutukso lang siya ng lalaki.
Like his words, Theo's voice was sinful. He had awakened something wicked inside her—something that Faith was powerless to control.


Early-maturing variety! Grow your own excellent dessert-quality fruit without the wait. Medium-height plants develop vigorous runners for increased berry production. Large, glossy berries are plump and juicy with a long conic shape. Flavor is outstandingly sweet and subacid with highly pleasing aromatic qualities. Developed by University of California and introduced in 1972. Disease-resistant to leaf spot. Cold hardy. Ripens in June and may bear into fall. Self-pollinating.
I am wanting to try different varieties. Have been very pleased with Stark Bros. product.
I planted these last year and they were the best strawberries I have ever grown.
Is this a june bearing or ever bearing plant? It says it may bear into fall?
BEST ANSWER: Although Sequoia is officially considered Junebearing, the plants produce like an everbearing strawberry in mild climates, putting on berries throughout the warm season.
Sequoia Strawberries: The add says "Grow your own excellent dessert-quality fruit without the wait." Does that mean first season fruit?
BEST ANSWER: You might see some fruit the first year, but we'd encourage you to pinch off most (if not all) of the flowers that appear the year they plant in order to let the plants establish the first year and fruit the next. "Without the wait" refers to the fact that Sequoia matures earlier in the year than other varieties.
Does the Sequoia Strawberry produce the same year I plant it? If I plant it this spring, will I be able to harvest at the end of June or July?
BEST ANSWER: You may get a few berries, and maybe a few more if you had planted in the fall, but Sequoia typically takes 1-2 years to bear a full crop.
how do i prune grape vines?
This says "pkg 25". Does this mean I will receive 25 individual plants? Also, what is the spacing requirement?
BEST ANSWER: Sequoia Strawberries are shipped bare-root, which means you'll get a bundle of 25 plants. They need a little room; space them 6 to 18 inches apart.
I Do recomend this strawberry plant. Good size as well as good flavor. The plants kept putting berrys on through out the summer. This was my first season so I am looking forward to next spring crop.
These strawberries grew like mad. They produced the first year and still put out nearly 4 times the plants. There were still green leaves in the winter and flowers early this spring. I even thinned them out this spring.
Didn't realize this was an everbearing strawberry. I never have good luck with the everbearers. Seems like the hot dry summers reduces the production. I was surprised to see more berries in late july, early august and then again in october and we picked berries up until thanksgiving. very pleaseantly surprised!!
This strawberry was no better than others I have used in the past. I planted four rows of new berries: sequuoia, cabot,, quinault, and surecrop. Sequoia was ranked third in this planting.
I love these big, healthy plants, and nice berries the first season. Waiting for current crop to develop but looks like a big harvest. I may replace some of my other berries with these plants.
Didn't fruit much first year. Seems like this year It will do better than last.
I give up trying to grow strawberries because the strawberries either were tiny small or diseased. I wish they turned out better because of the high recommendations and I really wanted to grow my own berries.


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text:
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Home > Mandel Graduate Unit > About the Unit > News & Events > Transitions Workshop: Four Sessions at a Career Crossroads
Transitions Workshop: Four Sessions at a Career Crossroads
In November and December 2016, the Mandel Graduate Unit held a "Transitions Workshop" that offered graduates a safe space in which to re-examine their vision and professional path
In the course of their studies at the Mandel School for Educational Leadership, fellows invest great efforts in developing their educational-social vision, and in thinking about the particular field in which they wish to create change. Afterward, throughout their professional lives, Mandel graduates are expected to pursue that vision, to continue refining it, and to effect change and make a difference wherever they may be.
At the same time, it is clear to the graduates themselves, and to the Mandel Graduate Unit that accompanies their professional development, that a vision is not a fixed concept, and that it must be dynamic and change. Over the years, graduates reach certain crossroads that force them to revisit and redefine their vision in order to decide what to do next.
The Mandel Graduate Unit's "Transitions Workshop" was designed to address precisely such junctions. It creates a safe space in which graduates can re-examine their vision and their professional path. Comprised of four sessions, the workshop was held in November–December 2016, and was led by Shahar Bar Yehuda, a graduate of Cohort 17; Granit Almog-Bareket, the director of the Mandel Graduate Unit, who is a graduate of Cohort 14; and Rakefet Mossek, the consultations manager of the Mandel Graduate Unit.
Three graduates – from Cohorts 1, 3, and 9 – participated in the workshop. All of the participants already had years of practical experience, held several successful management positions, and were weighing their next steps.
As part of the structured process, which took place in a small, intimate group of graduates at a similar professional juncture, each participant clarified and redefined his or her personal vision. As part of the process, the participants gained an understanding of the barriers they faced and how to overcome them, mapped the field in which they wish to act, and identified the steps necessary to reach the goals they set for themselves. The group was an active partner in the process; its members provided feedback, facilitated mutual learning, and offered alternative perspectives.
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May 30, 2017: Another big battle between Artemis Racing and Emirates Team New Zealand. It took until late in the race toward the final top mark that Emirates Team New Zealand pounced to take the lead and clock up another point. Peter Burling and Blair Tuke take us through the thriller.
May 30, 2017: Qualifiers Race Day 4 preview: Martin looks at the day ahead with Emirates Team New Zealand's Kevin Shoebridge. It's a rematch with Artemis racing, will it be as epic as yesterdays race?
Streamed LIVE May 29, 2017.
Summary of the third day of racing at the 35th America's Cup yacht race in Bermuda on May 29, 2017. Day three of the Louis Vuitton America's Cup Qualifiers was a day in which the five challenging teams; Land Rover BAR, Artemis Racing, SoftBank Team Japan, Groupama Team France and Emirates Team New Zealand, had their chance to enhance their positions on the leaderboard and close the gap on Defenders of the 'Auld Mug' and table-toppers ORACLE TEAM USA who sat out of action, having raced three times on day two.
May 28, 2017: Summary of Day #2 of sailing racing at the 2017 America's Cup in Bermuda, held on Sunday May 28 2017.
May 28, 2017: Two Races and two wins for Emirates Team New Zealand on what was described by Skipper Glenn Ashby as an incredibly tricky day in Bermuda!
Discover Bermuda's Great Sound | GoToBermuda.com: "Known as one of the world's best places to sail, Bermuda's Great Sound is a natural treasure for those who love being on the water. See how to experience it for yourself."
WMRT Porec Match Cup 2017 | World Match Racing Tour May 26-28, Croatia: "2017 marks the year when Porec picks up the torch and brings back the World Match Racing Tour to the Adriatic at Peskera Bay, Croatia. This World Tour level event will qualify the top two teams to the World Championship level event Match Cup America in September."
Video above published May 22, 2017: Boat Captain Feargal Finlay talks about the systems onboard a TP52 racing sailboat.
Video above published Mar 14, 2017: Step into the mind of a Tactician. Full Race with audio from tactician Terry Hutchinson! Multiple camera angles & Drone view of Race 8 in the 52 Super Series 2017 Miami Royal Cup. Video produced by Keith Brash.
Video above published May 19, 2017: He is the architect of the modern America's Cup and in the second part of our exclusive interview, Sir Russell Coutts describes how sailing's most prestigious event might influence sailing in the future. By the time teams launch their race boats, some will have built five boats for this America's Cup cycle. In the second part of our exclusive interview, Coutts talks candidly to World Sailing about how the future America's Cup may look.
Video above published May 10, 2017: What's under the skin of an ACC cat? With the help of Groupama Team France we take a look at what lies within the modern America's Cup Class designs and what makes them tick.
35th America's Cup (AC35) will be raced in Bermuda in June, 2017, with the Louis Vuitton America's Cup Qualifiers & Challenger Playoffs scheduled for 26th May – 12th June 2017.
Video above published May 15, 2017: Sir Russell Coutts is one of sailing's most decorated sailors. To add to the long list of World Championships he has an Olympic Gold medal and has won the America's Cup five times, three as skipper. But his reputation hangs on more than simply pointing a boat in the right direction. In 2010 he swapped the wheel for the reins and announced a bold, ambitious and controversial vision for the next America's Cup, the move to catamarans. And the Cup has never looked back. He talks candidly and exclusively to World Sailing.
Published May 24, 2017: Pure energy, pure entertainment and PURE PERFORMANCE – the TP52 World Championship had it all, and more! Next stop: Sardinia for the Audi 52 SUPER SERIES Sailing Week. Racing starts again on 21st June. Full recap here.
May 20, 2017:The ROLEX TP52 World Championship title all came down to this one, final race. Next stop: Porto Cervo for the Audi 52 SUPER SERIES Sailing Week. Racing starts again on 21st June.
Final Day 5 LIVE Video Replay of the Rolex TP52 World Championship Scarlino 2017.
The penultimate day of racing sets us up for a super Saturday showdown! Watch the final day LIVE, via www.52SUPERSERIES.com or through the app.
Day 4 of the Rolex TP52 World Championship Scarlino 2017 streamed LIVE May 19, 2017.
Published on May 19, 2017: Indulge yourself with these glorious images of the TP52s surfing the untouched Tuscan coastline in yesterday's Coastal Race. Watch Day 4 LIVE, via www.52SUPERSERIES.com or through the app.
Harm Müller-Spreer's German-flagged team on Platoon has taken over the lead of the Rolex TP52 World Championship, earning themselves a cushion of three points ahead of defending world champion Quantum Racing.
May 16, 2017--"The fleet is incredibly open, this is a challenging venue, and everybody is on."--Tuesday 16th May, Scarlino: After a long and challenging day on the waters off Scarlino, Tuscany, Quantum Racing – the defending champions – lead the Rolex TP52 World Championship by virtue of winning the one and only race sailed.
Venue: Marina di ScarlinoOn the western coast of Tuscany lies the Marina di Scarlino, one of the top racing venues in the Mediterranean. A modern and fully equipped marina, which hosts the Club Nautico Scarlino, is perched on the coastal side of Mount Alma and is starkly contrasted by the relatively untouched, medieval commune of Scarlino.
Video above published May 3, 2017: The America's Cup has always been about pushing the limits of technology in sailing, particularly in recent years. One of the hallmarks of the modern America's Cup is the introduction of foiling, reaching speeds never seen before and allowing the boats to literally "fly" above the water.
The America's Cup Revolution: There has been a revolution in the America's Cup - a shift from monohulls racing far offshore to incredibly fast, foiling catamarans raced close to shore by high-performance athletes. Yet over 166 years the spirit of the America's Cup has remained the same, with sailing's best and brightest pushing the boundaries to win the oldest trophy in international sport.
Video above published May 12, 2017: In this episode, America's Cup CEO Russell Coutts discusses the amazing progress Bermuda has made thus far with the construction of the AC Village and the readiness of the 6 teams to compete. Over the course of the final practice races, the teams will need to refine their techniques and prepare for the qualifiers in 2 weeks.
Video above published May 16, 2017: Stephen Murray Jr.'s Volvo 70 Warrior, finished the 2017 Antigua Bermuda Race on Tuesday 16 May 2017 taking Monohull Line Honours and setting the Monohull Race Record for the Antigua Bermuda Race of 3 days 20 hours 32 mins & 41 secs.
Video above published May 13, 2017: Start of the first Antigua Bermuda Race organised by the Royal Bermuda Yacht Club in association with Antigua Sailing Week. Sponsored by Goslings Rum and Bermuda Tourism.
Antigua Bermuda Race organised by the Royal Bermuda Yacht Club in association with Antigua Sailing Week: An impressive entry list is taking shape for the Antigua Bermuda Race which starts from Antigua on Friday 12th May, 2017. With 22 entries, including 17 over 50ft and seven Maxis and one SuperMaxi, the sight of the fleet departing for the 900 nautical mile race will be nothing short of spectacular. The variety of the fleet shows the wide appeal of the offshore race, attracting ocean going cruisers, round the world racing yachts, high performance multihulls, as well as classic designs. The latest entry to the Antigua Bermuda Race is the beautiful classic Bermudian yawl, Mariella, skippered by owner, Carlo Falcone. The 80ft (24m) Alfred Mylne-designed ketch was built entirely from wood by the legendary William Fife & Son yard in Scotland in 1938 and was lovingly restored by Carlo after being badly damaged in a hurricane. Mariella is now in fantastic condition and on top form having secured overall victory in the recent Panerai Antigua Classic Yacht Regatta.
One of the first yachts to enter the Antigua Bermuda Race was Spirit of Bermuda and there is more than meets the eye to the 112ft three-masted schooner. Just a couple of weeks before the start of the Antigua Bermuda Race, Spirit of Bermuda was racing with the giants at Antigua Classic Yacht Regatta. Spirit of Bermuda got the better of the 141ft (43m) Columbia and gave the professional crew on the 210ft (64m) Adix a run for their money. Spirit of Bermuda is owned by the Bermuda Sloop Foundation, the brain child of founder Malcolm Kirkland, with co-founders Jay Kempe and Alan Burland.
Bermuda to Port, finish off St David's Light Bermuda.
America's Cup, 26 May - 27 June, 2017, Bermuda: "There Is No Second"
In 1851 Commodore John Cox Stevens, a charter member of the New York Yacht Club (NYYC), formed a six-person syndicate to build a yacht with the intention of going to England and make money competing in yachting regattas and match races. The syndicate contracted with pilot boat designer George Steers for a 101 ft (30.78 m) schooner, which was christened America when launched 3 May 1851. On 22 August 1851, America raced against 15 yachts of the Royal Yacht Squadron in the Club's annual 53-nautical-mile (98 km) regatta around the Isle of Wight. America won, finishing 8 minutes ahead of the closest rival. Reportedly, Queen Victoria, who was watching at the finish line, asked who was second, the famous answer being: "Ah, Your Majesty, there is no second." The surviving members of the America syndicate donated the cup via the Deed of Gift of the America's Cup to the NYYC on 8 July 1857, specifying it be held in trust as a perpetual challenge trophy to promote friendly competition among nations. The America's Cup is the oldest international sporting trophy.
Video above published May 10, 2017, by AmericasCup.com: "Your Majesty, there is no second". A four-word phrase spoken to Queen Victoria in 1851 that to this day exemplifies the America's Cup and its winner-takes-all pursuit of excellence. The battle for the 35th America's Cup will be just as fierce as that first America's Cup, as there still is no second in the oldest trophy in international sport.
The key players of the 35th America's Cup talk about why this trophy is so coveted, so prestigious, and so difficult to win. Since 1851 the America's Cup trophy has represented the pinnacle of sporting achievement, and it is no different today.
The Martini Racing AC33: not only does it look the part, but it performs superbly in all conditions!
Antigua Sailing Week 2017: One of the favourites for the Lord Nelson Trophy, Ross Applebey's Oyster 48, Scarlet Oyster was called over the line at the start and did not return for some time. However, the Scarlet Oyster team rolled up its sleeves picking off the opposition one-by-one to scrape back into second position. Jonty Layfield's Swan 48, Sleeper X took the gun and the race win, but Scarlet Oyster is CSA 5 champion. In other hot classes, Sergio Sagramoso's Melges 32, Lazy Dog scored its fourth bullet. Bajan TP52, Conviction, skippered by Clint Brooks scored its seventh win, as did Maxi, Kialoa III and Sir Peter Harrison's Super Maxi, Sojana. There were also other prizes to win, including three of the CSA Class winners and Bareboat One, which were hanging in the balance.
Video above published May 5, 2017: Yacht racing highlights of 50th edition Antigua sailing week!
Video above published May 2, 2017: Its all go on race day 3 as leaders emerge in divisions A and B. Ride with a cutting edge Polish catamaran and with a team of German girls battling for the podium in their bareboat class.
Published Apr 24, 2017: Sights and sounds of Day Three at Sperry Charleston Race Week 2017 - the largest sailing event of its kind in the Americas.
Published on Apr 22, 2017: Sights and sounds of Day Two at Sperry Charleston Race Week 2017 - Charleston, South Carolina - the largest sailing event of its kind in the Americas.
Sperry Charleston Race Week - April 20-23, 2017: Race Week Culminated with Moderate Winds and High Spirits--After three days of intense competition across 16 different classes of sailboats, the biggest keelboat regatta in the Americas was filled with exciting racing, rockin' beachside parties and some great camaraderie.
Published Apr 27, 2017: SoftBank Team Japan and ORACLE TEAM USA lined up on the Great Sound in their new America's Cup Class boats, with very fast results--even at speeds of over 40mph the chase boat was struggling to keep up with these racing machines--as training and development continues in preparation for the 35th America's Cup.
Published Apr 27, 2017: We caught up with key personalities from each of the six America's Cup teams on the America's Cup 'preseason' that is practice racing. The teams are currently engaged in the third of four practice racing periods in their America's Cup Class boats, and seeing improvements every day.
Winding the clock back on a Volvo 65 and taking a race boat that already has over 40,000 hard miles under its keel might not be your idea of a perfect start for another lap of the planet. But the newly refurbished fleet of Volvo 65s are better than new. We went to Portugal to find out how this can be so. Plus, capsizing a $multimillion America's Cup catamaran raises heart rates. We find out how AC foiling works. We head to Palma for the Tropheo Princesa Sofia and then to Miami for the TP52 Super Series.
Over the next four years, SAP will bring its cutting-edge, innovative solutions to World Sailing's World Cup Series of events.
Video above published Apr 30, 2017--A 60 second round up from France.
See JohnTheCrowd.com: World Sailing's 2017 World Cup Series Hyeres, France, April 23-30 for all the video highlights!
Video above published Apr 30, 2017: The full Medal Race from France.


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Q: Formatting the jquery slider tool tip text How can i format the jquery slider tooltip text to percentage  (10-100%)?As im using d3 js. Thats is zoom.scaleExtent([0.2, 2]).
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When i slide I'm getting the values from 0.2 to 2 in the tooltip but i need it from 10% to 100%.  jsfiddle.net/fekkyDev/aVhd8/205

A: Try this out:- http://jsfiddle.net/adiioo7/aVhd8/206/
JS:-
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redpajama_set_name: RedPajamaStackExchange


Whether you love them or hate them - how will you eat yours?
At Christmas they served an entire Christmas dinner covered in batter and now one Devon fish and chip shop has gone one step further for Easter.
Marshall's Fish Bar in Cullompton is serving up battered Creme and caramel eggs - as well as battered Easter biscuits this April.
And chip shop owner Andrew Marshall describes the battered Creme Eggs as 'gooey gorgeousness'.
He said: "It's not as a elaborate as the battered Christmas dinner but we have already put deep fried Creme Eggs and caramel eggs on the menu, as well as Easter biscuits.
"We did try to batter Hot Cross Buns but they didn't come out very well, so we hope our customers like the biscuits just as much."
The battered Creme Eggs are priced at £1.50 each and the biscuits are £1 each.
At Christmas Andrew had a lot of positive feedback about his battered Brussel Sprouts, so he decided to serve an entire Christmas dinner covered in batter.
The dinner included a chicken leg, battered sprouts, battered carrots, battered pig in a blanket, battered stuffing ball, a gravy bomb (which is a gravy ice cube wrapped in mash potato and bread crumbs) and to finish it off a battered mince pie.


TECHNICAL SPECIFICATIONS Owner: ILVA S.p.A. in Amministrazione StraordinariaGen. Contractor: Cimolai SpACovered Area: 355,600 m2Description: as part of the environmental renovation work to be carried out at the ILVA plant in Taranto, Cimolai was awarded the design, manufacture and assembly of the Mineral and Fossil Parks Safe Confinement. It's a double steel structure, 80 m high, 254 m wide, and 700 m long, with a total weight of about 60,000 t.


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The 10 Most Beautiful Places to Stay in Montenegro
Petrovac | © Olena Z/Shutterstock
Sarah Pavlovic
Updated: 28 September 2017
What to choose, what to choose? Will it be five-star seaside luxury or atmospheric old town? Maybe a holiday spent wandering mountain trails and picking wildflowers? Or a complete retreat? In a land that's both stunning and diverse, here are the top 10 most beautiful places to stay in Montenegro.
Hands down one of the most beautiful places in Europe, Sveti Stefan is a stunning place to stay in Montenegro. A former royal summer residence, Sveti Stefan is gifted with pink pebble beaches, a 15th-century stone and terracotta islet, a forest park of old olive trees, an old palace and sunset views to die for.
The top place to stay here is five-star Aman Sveti Stefan, but there are also lots of budget-friendly hotels with killer views in this natural paradise.
Sveti Stefan, Montenegro
Sveti Stefan | © Anton Nikiforov/WikiCommons
Porto Montenegro
Wake up to the view of bajillion-Euro superyachts bobbing on bright blue waters. Porto Montenegro's palm tree-lined streets and pastel buildings epitomises the Mediterranean lifestyle. Wander down to a waterside café for brunch, get a massage and then spend the afternoon soaking up the sun at the Lido pool. At night, Porto Montenegro's village restaurants come alive and there are two clubs open until late.
The TYHA platinum-rated marina is also just steps from Tivat town, where visitors can take boat tours, find great restaurants, nightlife and swim spots. Five star Regent Porto Montenegro has rooms from €180 per night.
Porto Montenegro, Obala bb, Tivat, Montenegro, +382 32 660 700
Porto Montenegro | © Katja Hasselkus/Flickr
Perast's palace-lined shore shows the glory of an era where Bay of Kotor sailors were some of the richest in the Adriatic. This picturesque township has been protected from modern construction and all the buildings in the town adhere to the traditional stone architecture of the bay.
Perast is ideally positioned opposite the Verige Strait, so visitors have an ever-changing view of boats passing. As if that wasn't enough, the two island churches just offshore complete the picture. Visitors love staying here for the beautiful views and because it's a car-free town, they can stroll along the seaside to their favourite restaurant for a candlelit dinner by the sea.
Perast, Bay of Kotor, Montenegro
Perast | © Imke.stahlmann/Flickr
Petrovac, on the Budva Riviera, is a small town on the shores of the Adriatic Sea. The long stretch of beach and warm waters are the ideal playground for holidaying families in summer, while the boardwalk is dotted with traditional stone houses, restaurants and boutiques.
Castel Lastva, the 16th-century fortress at the northern end of the town, juts out into the bay and two islands float just offshore. Not only is this idyllic Mediterranean township a beautiful place to stay, it's close to key attractions like Budva and Skadar Lake.
Petrovac, Montenegro
Skadar Lake
Although the Montenegrin coast gets most of the attention, Skadar Lake is one of the most beautiful places to stay in Montenegro. The lush greenery, quaint townships and solitude make this a haven for nature-lovers. An important wetland, the lake is always teeming with wildlife, especially migratory birds. The Dalmatian Pelicans are a must-see here and tours on cuns (traditional fishing boats) take people out to see the birds.
This area is also known for its excellent boutique wineries and wine tastings start from just €10. It's also the ideal place to try local rakija (brandy), honey, ham, cheese and carp from the lake.
Skadar Lake, Montenegro
Skadar Lake | © monticello/Shutterstock
Herceg Novi overlooks the entrance of the Bay of Kotor, with Montenegro on one side and Croatia on the other. Each side of the bay is adorned with Austro-Hungarian fortresses and Mamula, a fortressed island, sits in between. Herceg Novi has the best beaches in the bay and warm, clear water to boot. A 7km seaside promenade called Setaliste Pet Danica connects dozens of tiny, pebble beaches and the central marina just below the old town.
In the old town, violins in the music school serenade passersby, while Belavista Square is the place to catch up with friends over a coffee.
Herceg Novi, Bay of Kotor, Montenegro
Herceg Novi | © BelaBela/WikiCommmons | © BelaBela/WikiCommmons
Hotel Astoria | @ Courtesy of hotel
Kotor's Venetian old town is tucked into towering mountains and fronted by the glittering waters of the Bay of Kotor. Its winding alleyways reveal boutique hotels, traditional eateries, museums and historic churches. It's one of the most beautiful and atmospheric places to stay in Montenegro. In front of the old town, a promenade passes a marina full of yachts and the palaces of Dobrota. Behind the town, San Giovanni Fortress is a challenging hike, but the views are worth every step!
Kotor, Opština Kotor, Serbia And Montenegro
Like Kotor, Budva old town is hard to beat for beauty and atmosphere. The walled town is flanked by a marina full of glittering yachts and overlooks Sveti Nikola island. Budva is known for its fantastic beaches and right in front of the old town, Ricardova Glava beach is the perfect place to cool off and enjoy the Montenegrin sunshine.
Budva, Montenegro
Budva | © my Life, the Universe and Everything/Flickr
One of the hidden gems of Montenegro, Durmitor National Park is a hiker's paradise. Montenegro's second-highest peak, Bobotov Kuk, is a popular hike throughout the summer months. For those wanting more relaxing activities, a scenic stroll around the Black Lake followed by a picnic is the ideal way to enjoy the park's stunning scenery. Bears and wolves roam Durmitor's rugged mountains and the local villages offer a snapshot of traditional Montenegrin lifestyle.
Durmitor National Park, Montenegro, +382 52 361 337
Durmitor National Park | © Ky0n Cheng/Flickr | © Ky0n Cheng / Flickr
Lustica Peninsula
For those seeking a true getaway, there's no better place than Lustica Peninsula. Crystal-clear sea and miles of olive groves and wild bush make Lustica Peninsula is a true haven. With nothing more than a book and an ever-changing sea view, your batteries are guaranteed to be recharged.
Lustica Peninsula, Montenegro
Lustica Peninsula | © nadtochiy/Shutterstock


Recent research from Edinburgh's Heriot-Watt University found short bursts of intensive exercise can be as effective as the government recommended 5 or 6 hours a week.
High-intensity interval training (HIT) can be done on an exercise bike (as in the study), running upstairs or even running on the spot. Basically anything will do as long as the body is pushed to the maximum.
Timmons advises four 30-second bursts of exercise with the whole thing taking about 4 minutes. He says doing this even twice a week will bring clear benefits. The article goes on to explain the study which involved 16 average and relatively sedentary 20-year-old men before and after a 2-week training period, in more detail.
After two weeks of HIT training the men had a 23 per cent improvement in how effectively they used insulin to remove glucose from the bloodstream. Timmons says similar ongoing studies in Canada are showing that the risk of heart attack could also be cut with this type of training.
Timmons believes his findings could help the NHS make big savings: "This novel approach may help people to lead a healthier life, improve the future health of the population and save the health service millions of pounds simply by making it easier for people to find time for exercise".
Frank Forencich, the international natural fitness expert and founder of Exuberant Animal.com is, however, not wholly convinced: "It may motivate some people to better health practices, which is great.'' He went on "However, we have to think of it in context. In our natural state, as hunter-gatherer tribes the vast majority of physical movement was walking, which involved scouting and gathering.


Hard to write a comprehensive tennis roundup when we are midway through the first major of the year. But suffice to say it's been an exciting week, with Frances Tiafoe and Stefanos Tsitsipas finally delivering on some Next Gen promise with their wins over Grigor Dmitirov and Roger Federer, respectively. How I'd love to see one of them win it all.
And while Serena Williams is looking unstoppable -- as with the Big Three, when is it enough? -- I won't exactly be disappointed if she ends up tying Margaret Court's apples-to-oranges record on the stadium that bears the homophobe's name.
UPDATE: All credit to Simona Halep for coming back from a disastrous first set to give Serena a real run for her money. The GOAT was too good to overcome, but I have a newfound respect for the Romanian pipsqueak's game -- and box.
Milos Raonic made Alexander Zrerev look like a "major" fool again. But as I said before, any chance to see what's in the Balkan Canadian's box is fine with me.
The Croatia-Serbia battle between Borna Coric and Filip Krajinovic was a sight to behold. Glad Borna pulled it out. Next up is Luca Pouille in what promises to be the Battle of the Bubble Butts.
And ... did you see Ash Barty edge out Maria Sharapova?
How many legends can you name?
Pouille came from a set down to beat Coric. Starting to think the Croat might not have what it takes to go to the next level. Weird how many players have problematic forehands these days, from Borna and Benoit to the hitches on Tiafoe, Khachanov and even Medvedev.
ughhh.. Borna lost that's a drag...but the Frenchy with the oversized behind was the better player...barely.


text:
Bellanwila Rajamaha Viharaya is a Buddhist temple situated in Bellanwila, Colombo District, Sri Lanka. Located around 12 km south to the Colombo city, near Dehiwala - Maharagama road, the temple attracts hundreds of devotees daily and is famous for its annual Esala Perehera festival which usually takes place in the month of August or September. One of the most venerated Buddhist temples in Sri Lanka, many devotees flock to worship the sacred Bo tree of Bellanwila Rajamaha Vihara, which is considered to be one of the first offshoots of Jaya Sri Maha Bodhi in Anuradhapura, Sri Lanka.
The present chief incumbent of Bellanwila Rajamaha Vihara is Ven. Dr. Bellanwila Dhammaratana Nayaka Thera.

History and revival
There is literary evidence in ancient texts such as the Sinhala Bodhivamsaya which records that the Bodhi-tree in Bellanwila as one of the thirty-two saplings that sprang from the sacred Jaya Sri Maha Bodhi at Anuradhapura planted in the 3rd century BC. Bellanwila is also mentioned in the literary works of the 15th century, when Kotte, which is located close to Bellanwila, became the capital of the country. In the Kotte period Buddhism rose to great heights with the royal patronage of King Parakramabahu VI (1412-1467), who was the last native sovereign to unify all of Sri Lanka under one rule before the European colonial invasions.

The story of the revival of Bellanwila Viharaya is closely linked with Attidiya, a village adjoining Bellanwila. This sacred place was abandoned after the Portuguese invasion of the country's coastal areas. It was rediscovered by an adventurous monk known as Thengodagedara Hamuduruwo, who is said to be the founder of Galauda Viharaya.
One day in 1850, when he was traveling by boat along the Katu-ela stream towards Pepiliyana, it is said that he heard the sound of drums from a nearby thicket. Being inquisitive, he left the boat and walked towards the sounds. As he approached, the drum sounds faded away and he was surprised to see a Bodhi-tree. Subsequently, he came to discover that this was one of the thirty-two saplings from the sacred Bodhi-tree at Anuradhapura.
With the help of villagers, Thengodagedara thera cleared the land around the tree and built a modest shelter for monks. With this modest and mysterious beginning, Bellanwila began to attract the attention of Buddhist devotees in the neighbourhood.

Since Thengodagedara thera rediscovered Bellanwila, the temple has had a succession of chief monks such as Udugampola Sri Ratanapala thera, Udugampola Sri Dammakkhandha thera, Abhidhammika Weboda Sri Sangharatana thera, Asgiriye Devarakkhita thera and Bellanwila Sri Somaratana thera. It is Ven. Bellanwila Sri Somaratana thera, who became the chief incumbent of the temple in 1947 must be given the credit for raising Bellanwila Rajamaha Vihara to its present status.
He began the task of developing the temple and he himself designed the structural concept of the temple complex taking the image house of Polonnaruwa as the model. After the demise of Bellanwila Sri Somaratana thera, his pupil prof. Bellanwila Wimalaratne Thera has continued the development work of the temple.

A recent addition to the temple is a set of murals, that adorn the inner walls of the shrine hall (Budu-Ge). These murals which were painted by artist Somabandu Vidyapathy, depict in different strokes the life of the Buddha and Buddhism. In addition to the main shrine hall there are shrines dedicated to popular deities of Sri Lanka such as Vishnu, Katharagama, Saman, Vibheeshana, Suniam, Dedimunda, Natha and Pattini Matha, housing their symbolic images. These shrines which are situated right round the Bodhi tree, also depict the architecture of Polonnaruwa period.

The Sacred Bo Tree
The Bellanwila temple is known mostly for the sacred "Bellanwila Bo Tree" which is  2300 years old.  The Bo tree is considered as one of the first Thirty two saplings (Young trees) which arose spontaneously from Jaya Sri Maha Bodiya- Anuradhapura on the seventh day of its plantation ceremony. The King Dewanampiyathissa who has planted the "Jaya Sri Maha Bodhi" has invited prominent ruling heads from each respective area of the country and handed over these thirty two saplings to be planted in their ruling areas. Sri Maha Bodiya was planted in 288 BC which is 2300 years back. The thirty two saplings including "Bellanwila Bo Tree" are only seven days younger to Sri Maha Bodhiya. From these thirty two saplings only four to five Bo Trees Including "Bellanwila" are survived or recognizable today.

Esala festival
The simple Bellanwila Esala perehera (procession) that was started in 1947 under the instructions of Bellanwila Somaratana Nayaka Thera has now grown into a famous colorful pageant, which attracts large crowds annually. Today it is one of the most famous annual cultural pageants in Sri Lanka. The Esala festival of Bellanwila,  which is usually held throughout a week in the month of August or September in every year, draws many devotees from the district of Colombo and from other parts of the country. The attraction is not only for the colourful features of the procession itself, but more so for the religious activities that leads up to the main event. Bellanwila esala festival includes Dhamma Desana sessions (religious sermons) which draws many devotees to the temple. Invoking of blessings starts with a week long Pirith chanting, which is followed by the processions that parade in the neighborhood of Bellanwila during the nights of Esala festival.

The Bellanewila Esala festival consist of a series of processions, namely Deva-dootha Perahera, Kumbal Perahera, Mal Perahera, Paawaada Perahera, Ransivili Perahera and Randoli Perahera. The Diya Kapeema Perahera and Deva Daanaya  which concludes the esala festival, follows the Randoli Perahera which is held in the final night of the festival. The Bellanwila Esala procession usually consists of drummers, dancers (low-country and up-country), decorated tuskers and trumpeters who parades the neighbourhoods of the Bellanwila temple premises. Lantern bearers, together with devotees who carry Buddhist flags also take part in this grand display of religious piety, which portrays the Buddhist cultural and artistic heritage of Sri Lanka.

References

External links
Bellanwila Rajamaha Viharaya (official website)
Historic Bellanwila Rajamaha Vihara (Amazing Lanka)

Buddhist temples in Colombo District
Stupas in Sri Lanka


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Main / Strategy / Microsoft xp compatibility mode
Microsoft xp compatibility mode
Name: Microsoft xp compatibility mode
30 Apr Most programs created for earlier versions of Windows will work in this version of Windows, but some older programs might run poorly or not at all. Running the Program Compatibility Troubleshooter should automatically detect and fix some of the most common issues. First, select Run. 19 Oct Windows XP Mode for Windows 7 makes it easy to install and run many of your productivity programs that run on Windows XP directly from a. 7 Aug According to the Microsoft knowledge base article, compatibility mode is a feature of Windows that allows you to run programs written for earlier.
9 Jan Thankfully there is a compatibility mode that can be easily set per You can choose to run the program in Windows XP compatibility mode. 24 May If this doesn't work, there's another work-around: XP Mode. (And yes, I know it's silly that the two solutions are called XP Compatibility Mode. 21 Sep What are Windows Virtual PC and Windows XP Mode? Windows Virtual PC is the latest Microsoft virtualization technology for Windows, and is.
22 Oct Does Windows XP software work on Windows 10? The simplest way is to use Window's built-in compatibility mode, which instructs Windows. 17 Jan Although Windows XP, Vista, and 7 all have bit versions availa. Although Microsoft has done a good job of maintaining compatibility when. In response to this, every time Microsoft Click "Next." 3. Select the program you want to run in Windows XP compatibility mode and click "Next." 4. Select the . If you get any strange problems from an XP application or keyboard, check that Compatibility Mode hasn't been. 24 Aug If one of your favorite applications doesn't run properly in Windows 10, you can set to run in WIndows 8, 7 or XP compatibility mode. app, try different settings, or report the problem to Microsoft and view help articles online.
18 Feb However, in most cases, you can try to use the compatibility mode for Windows XP or Windows 7 that refuses to run on Windows 10, you. 17 Sep With Windows 7, Microsoft has abandoned the hope of maintaining direct Windows XP Mode comes the closest to an OS virtualization, albeit without problems that can't be solved with the 'regular' compatibility mode. Originally, this page was written for Windows XP alone but Windows Vista has a similar capability. For those in between, there is some hope in using Windows XP's Compatibility Mode. Open an Explorer window and navigate to the. A compatibility mode is a software mechanism in which a software either emulates an older Examples include Classic Mode in Mac OS X and Windows 's / Windows XP's / Windows Vista's / Windows 7's compatibility mode, which Internet Explorer 8 was promoted by Microsoft as having stricter adherence to W3C.
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text:
Egypt Unveils 4,400-Year-Old Tomb Near Cairo
Updated Feb. 03, 2018 2:59PM ET / Published Feb. 03, 2018 2:39PM ET
Amr Abdallah Dalsh/Reuters
Egyptian authorities on Saturday unveiled a 4,400-year-old tomb recently discovered near Cairo. The country's Antiquities Ministry said the tomb is thought to have belonged to a priestess known as Hetpet in the 5th Dynasty. "We know of course that she was a high official and that she had a strong link with the royal palace," Egyptian Antiquities Minister Khaled al-Anani told reporters. The tomb, found near the Great Pyramid of Giza, is made of mud brick and adorned with wall paintings that show Hetpet in various scenes. Other scenes depict a monkey, an animal that was commonly kept as a domestic pet in pharaonic times. Mostafa al-Waziri, who led the excavation mission, said he expects more discoveries will be made in the "promising area" in the near future. "What we see above the earth's surface in Egypt doesn't exceed 40 percent of what the core holds," he said.
Read it at Associated Press


text:
Saccharomyces cerevisiae (pivní, pekařská nebo vinná kvasinka) je druh kvasinky z oddělení vřeckovýtrusných hub, která je člověkem v kvasných procesech používána už od neolitu. Pro kvašení byly nejdříve využívány kvasinky přirozeně se vyskytující na povrchu ovoce nebo na slupkách bobulí révy vinné a není jasné kdy došlo k "domestikaci" těchto kvasinek. Kvasinky saccharomyces cerevisiae je možné rozdělit do geneticky spřízněných kmenů podle toho, jaký substrát kvasí, přičemž hlavní jsou pivní, pekařské a vinné kvasinky; samotné vinné kvasinky mají podle analýzy genetické příbuznosti až na několik výjimek společný původ a byly domestikovány 8000-10000 př. n. l.

Buňky S. cerevisiae jsou oválné až kulovité, velké 5-10 mikrometrů. Pivní kvasinka se rozmnožuje speciálním typem dělení, které je typické pro kvasinky – tzv. pučení.

Pivní kvasinka je jedním z nejstudovanějších eukaryotních organismů z hlediska molekulární a buněčné biologie, významná je především pro studium buněčného cyklu, vnitrobuněčné signalizace a protein-proteinových interakcí.

Modelový organismus

Saccharomyces cerevisiae se v molekulární biologii využívá jako modelový organismus pro studium eukaryotní buňky. Představuje jeden z nejjednodušších eukaryotních organismů, což umožňuje její snadnou a levnou kultivaci v laboratorních podmínkách. Přitom velká podobnost mezi proteiny i buněčnými pochody vyšších eukaryot umožňuje výsledky získané studiem Saccharomyces cerevisiae zobecnit i pro složitější organismy.

Mezi hlavní příčiny oblíbenosti Saccharomyces cerevisiae jako modelového organismu patří schopnost žít jako haploid, což usnadňuje tvorbu delečních kmenů, aktivní homologní rekombinace umožňující efektivní přípravu geneticky modifikovaných kmenů a nízká komplexita genomu obsahující malé množství nekódující DNA. Díky tomu byla pro Saccharomyces cerevisiae vypracována celá řada postupů a stala se tak prvním eukaryotním organismem, jehož sekvence DNA byla zjištěna sekvenováním. Genom kvasinky je stále v centru pozornosti vědců, kteří zkoumají základní principy genetiky a fyziologie. Genom S. cerevisiae se skládá z přibližně 13 000 000 párů bází a z 6275 genů, přestože jen okolo 5 800 z nich se považuje za opravdu funkční geny. Až 31 % genů kvasinky saccharomyces cerevisiae může být homologní s lidskými geny.

Využití Saccharomyces cerevisiae:
 klasické genetické postupy, například tetrádová analýza
 studium buněčného a životního cyklu kvasinek
 zkoumání interakcí mezi proteiny pomocí kvasinkového dvouhybridového systému a jeho modifikací
 modelový organismus pro studium lidských nemocí

Životní cyklus

Existují dvě základní životní formy buněk kvasinky, haploidní a diploidní. Haploidní buňky prochází prostým životním cyklem (mitóza, růst, smrt). Diploidní buňky (typická pro kvasinky) procházejí podobným životním cyklem, ale v zhoršených životních podmínkách (stres) začnou sporulovat – vytvářet haploidní spory. Dvě spory posléze splynou (konjugují) v novou buňku.

Kvasný proces
Saccharomyces cerevisiae je jednou z hlavních pivovarských kvasinek, (společně s Saccharomyces carlsbergensis a Brettanomyces) především u rychle kvašených piv. Tyto kvasinky vytvářejí poněkud sladší druhy piv. Pivní pocházejí z kvasinek evropského hroznového a asijského rýžového vína.

Odkazy

Reference

Externí odkazy

 Saccharomyces genome database

Modelové organismy
Kvasinkovité


text:
Syndiamesa chuzemagna är en tvåvingeart som beskrevs av Sasa 1989. Syndiamesa chuzemagna ingår i släktet Syndiamesa och familjen fjädermyggor. Inga underarter finns listade i Catalogue of Life.

Källor

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chuzemagna


DALLAS – Here are the seven secrets to a long life: Stay away from cigarettes. Keep a slender physique. Get some exercise. Eat a healthy diet and keep your cholesterol, blood pressure and blood sugar in check.
• Never smoked or quit more than one year ago.
• Body mass index less than 25.
• Get at least 150 minutes of moderate exercise or 75 minutes of vigorous exercise each week.
• Meet at least four of these dietary recommendations: 4 1/2 cups of fruit and vegetables a day; two or more 3.5-ounce servings a week of fish; drink no more than 36 ounces of sugar-sweetened beverages a week; three or more 1-ounce servings of fiber-rich whole grains a day; less than 1,500 milligrams a day of salt.
• Total cholesterol of less than 200.
• Blood pressure below 120/80.
• Fasting blood glucose less than 100.
The heart association found just that in a recent survey that showed 39 percent of Americans thought they had ideal heart health, yet 54 percent of those had been told they had either a heart disease risk factor or needed to make a lifestyle change to improve heart health, or both.


text:
54 Albums Later, Connie Smith's Defiant Heart Has Plenty to Say
On Friday, Smith will release album 54, "The Cry of the Heart," her debut for the independent label Fat Possum and first secular recording in about a decade, after intermittent forays into gospel. While country music is no stranger to a comeback, since the 1990s many of the genre's figureheads have been resuscitated by studio wizards and the enthusiasm of younger generations. But "The Cry of the Heart" takes a different path, where resurgence doesn't mean reinvention: It's produced by the country musician Marty Stuart, 63, whom Smith married in 1997. The album's tender piano chords, steel guitars and lush analog quality recall Smith's '60s era recordings, a template known as the "Connie Smith Sound."
"Connie is the ultimate outlaw," Stuart said in an interview. "Most people's definition is get drunk, get crazy, act foolish. Her version is stick to your guns. Be who you are at any cost."
Connie Smith's fierce individualism sprouted from a tough foundation. "I was born a fighter because I was born into an alcoholic family," she said. Raised in Southern Ohio by her mother, Wilma Lily, and stepfather, Thomas Clark, Smith came of age among 14 siblings and stepsiblings. Her stepfather played mandolin at square dances and her three sisters sang.
"I tried to sing with them but he'd run me out because I was messing it up when I was trying to learn harmony," she said. The family would tune its battery-powered radio to broadcasts from the Grand Ole Opry, and Smith became enamored with the music of Kitty Wells and the Louvin Brothers.
Smith made her stage debut during her senior year of high school at a local square dance, where she earned $3 for performing a cover of the pop standard "My Happiness." A few years later, in August 1963, she entered a talent contest at Frontier Ranch, a bygone country music park near Columbus, Ohio, and won with a spirited rendition of Jean Shepard's "I Thought of You." She was awarded five silver dollars and a slot at the Grand Ole Opry opening for the singer and songwriter Bill Anderson. With his help, Smith landed a recording contract with Chet Atkins at RCA Victor in June the following year. She tracked her debut 45, "Once a Day" backed with "The Threshold," both written by Anderson, on July 16 at the label's famed Studio B.
Its immediate success was dizzying. "I'd have somebody pulling me on one arm, and somebody else pulling me on the other arm," Smith said of a D.J. convention she attended amid the sudden burst of fame. The setting was new to her and a bit stressful, but while bouncing between meetings she saw a man coming up the hall. "Before I could almost recognize who it was, he was singing" — she lowered her voice in a countrified croon — 'Once a daaay/All day looong.'" It was George Jones. Soon, another great, Loretta Lynn, was offering her advice, woman to woman.
"She told me who to trust and who not to trust, where to go and where not to go," Smith recalled.
As the years went by, Smith repaid the favor and served as a beacon for a younger generation of women in the industry. "She's one of those artists that's always been great," the country singer Tanya Tucker said in an interview. "She never goes out of style."


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