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Biochemical tricks of the hibernating bear – Science Daily

Posted: February 20, 2017 at 5:42 am

Winter is in full swing, and many of us have fantasized about curling up in a warm cave and slumbering until the warmth of spring arrives, just like a bear. Bears have the ability to sleep away the harsh winter months when food is scarce. They can spend five to seven months in hibernation. During this time, bears do not eat, drink, excrete or exercise. Despite the length of inactivity, bears do not experience bone loss, muscle loss, heart complications or blood clots like humans do during extended bouts of inactivity.

In a recent paper published in the Journal of Biological Chemistry, Karen Gjesing Welinder at Aalborg University in Denmark and colleagues set out to understand how wild Scandinavian brown bears protect their health and save energy during hibernation.

“The bear’s tricks for hibernation adaptations can inspire and teach us to prevent effects of the restricted mobility of astronauts and of long-term hospitalized patients,” says Welinder. “Immobile people lose muscle and bone mass, get blood clots, atherosclerosis and cardiac diseases. Immobile bears do not. Our deeper understanding of the tremendous physiological placidity encoded in animal genomes might be exploited in healthier lifestyles and medical treatments.”

To understand how bears maintain their health during hibernation, Welinder and colleagues decided to look for differences in the levels of blood constituents between hibernating and nonhibernating brown bears. The molecules circulating in the bloodstream play important roles in cellular defenses, nutrient transport and cell signaling. The researchers used a multitude of screening tools in this study to analyze the molecular components in the blood, including mass spectrometry-based quantitative proteomic, metabolomic and hematological analyses of blood cells.

The investigators discovered that the bears’ secret to maintaining their health during hibernation lies in saving energy on protein synthesis. During hibernation, complex pathways with many proteins are turned down or eliminated and are replaced with a small number of proteins with broader specificity and wide ranges of functions. This switch from complexity to simplicity allows bears to decrease the energy necessary to maintain important molecular processes for survival during hibernation.

Welinder and colleagues found that while the large majority of protein levels decreased during hibernation, the overall protein concentration increased due to dehydration and an increased level of serum albumin. The change allowed the bear to spend less energy synthesizing proteins to maintain functional protein concentration levels. Additionally, protein degradation was repressed by a 6 C decrease in body temperature and an increase in expression of alpha-2-macroglobulin, a broadly acting protease inhibitor. This further saved energy on costly protein synthesis by decreasing protein turnover.

Welinder and colleagues found that even though protein expression decreased overall, there were a few select proteins that were drastically elevated during hibernation. Bile salt-activated lipase, which can hydrolyze both triglycerides and cholesterol esters, was elevated 32-fold during hibernation and allowed the bears efficiently to harvest energy from stored fat. Only the three central coagulation factors, fibrinogen, thrombin and factor Xa, were increased during hibernation; together, these factors facilitate wound healing, only permitting local formation of blood clots when needed. Furthermore, the immune response was simplified to a few antimicrobial proteins, such as lysozyme, which acts as the innate line of defense against infection.

The sex hormone-binding globulin increased a dramatic 45-fold during hibernation, suggesting that this molecule must play a central role in the maintenance of hibernation. Welinder says the mechanism of action of sex hormone-binding globulin during hibernation still remains elusive.

Story Source:

Materials provided by American Society for Biochemistry and Molecular Biology (ASBMB). Original written by Amber Lucas. Note: Content may be edited for style and length.

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Biochemical tricks of the hibernating bear – Science Daily

Recommendation and review posted by Guinevere Smith

Scam Alert: Anatomy Of An Inheritance Fraud Letter – Forbes

Posted: February 20, 2017 at 5:41 am


Forbes
Scam Alert: Anatomy Of An Inheritance Fraud Letter
Forbes
My wife received a letter from Canada the other day. It was neatly typed, but had no return address. The first paragraph sounded promising, noting an "inheritance opportunity" with "genuine intentions." Not suprisingly, letters that start this way are

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Scam Alert: Anatomy Of An Inheritance Fraud Letter – Forbes

Recommendation and review posted by Guinevere Smith

Anatomy of an energy crisis – a pictorial guide to the tightening market, Part 2 – The Conversation AU

Posted: February 20, 2017 at 5:41 am

In the second in my series on the crisis besetting the National Electricity Market (NEM) in eastern Australia, I look at the tightening balance of supply and demand.

Australias NEM is witnessing an unprecedented rise in spot, or wholesale, prices as market conditions tighten in response to a range of factors.

As shown above, spot prices are typically highest in summer, due in large part to the way extreme heat waves stretch demand. The historical summer average across the NEM is around $50/MWhour. As recently as 2012, summer prices were as low as $30/MWhour. With only a few days to go in the 2017 summer, prices are averaging a staggering $120/MWhour on a volume-weighted basis. Many factors have played a role, including hot weather, and the drivers vary from state to state.

In South Australia, the high prices have been accompanied by a series of rolling black-outs culminating on 8th February. Spot prices are more than twice last summer, on a volume-weighted basis, and three times the summer before that. Volatility has increased markedly, as evidenced by the way the volume-weighted price has diverged from the averaged spot price.

But the price rises and security issues have not been restricted to South Australia, with Queensland and New South Wales experiencing steeper rises in percentage terms. Current Queensland volume-weighted prices are averaging $200/MWhour, some 300% above the long-term summer average.

On the 12th February new demand records were set in Queensland, with prices averaging $700/MWhour across the day. New South Wales narrowly averted load shedding on 10th February as temperatures and spot prices soared. So far, the exception has been Victoria, where summer prices have remain relatively subdued, at levels not far above the recent average.

Demand for electrical power varies over a range of time-scales, from daily, weekly to seasonal, as well as with longer-term economic trends. A key determinant in how much power is needed on any given day is the maximum daily temperature. As shown below, the maximum daily demand marks out a characteristic boomerang shape when plotted against maximum daily temperature. The boomerang bottoms out at temperatures of around 25C when air conditioning loads are at a minimum.

As illustrated above, demand increases significantly in response to heating loads as the weather cools below 20C and cooling loads as the weather warms above 30C. The difference in demand across the weather cycles can be substantial. For example, in South Australia the maximum daily demand varies from around 1500 megawatts on a day with a maximum temperature of 25C to around 3000 megawatts during heatwaves when the temperatures exceed 40C. With minimum daily loads under 1000 megawatts, This implies well over half the generation capacity in South Australia is needed to meeting peak demand in extreme days, with much of it sitting idle waiting for extreme hot weather events. To recoup costs in an energy-only market like the NEM, such peaking capacity demand extreme pricing accompany its dispatch. In reality to manage risks, such capacity is normally hedged at a cap-contract of around $300/MWhour

Similar patterns apply in other states, although in percentage terms the range is less severe. In Queensland the increase between 25 and 40 degree days is about 2000 megawatts or approx 30%.

A comparison of the figures above show some subtle but important differences in the South Australia and Queensland markets. Notably, the diagrams show that annual demand in Queensland has been rising progressively over the last four years, while it has been static in South Australia. The extreme weather of Sunday 12th February set a new demand record in Queensland, and well above any previous weekend day. In contrast, the 8th February peak in South Australia was lower than previous peaks. To understand why spot prices spiked to similar levels in the different regions requires a deeper dive into the local market conditions.

One reason for seasonal variability in prices is the natural variability in weather conditions, and particularly the frequency and intensity of heat waves. As illustrated below, the 2017 summer in Adelaide has been rather normal in terms of weather extremes, so far with only six days above 40C compared to seven last summer and thirteen in the 2014 summer. To date, the mean maximum is around 29.7C , more-or-less spot on the average over the last five years. As such weather variability would not seem to be the key factor driving the recent dramatic rise in spot prices.

The most significant change in the South Australian market last year was the closure in May of its last coal fired-power plant – Alintas 520 megawatt capacity Northern Power Station. Along with questions about long-term coal supply, Alintas decision to close had a lot to do with the low spot prices back in 2015.

Back then, spot prices were suppressed on the back of a fall in both domestic and industrial demand as well as the addition of new wind farms into the supply mix. As shown below, the rapid uptake of solar PV in South Australia had impacted the demand for grid based services, especially during summer, limiting price volatility, and affecting generator revenue streams via a lowering of forward contract prices. In combination, the conditions made for a significant excess in generating capacity, or capacity overhang.

Despite the falling average demand, and a changing load distribution, the peak demand during the recent heat wave reached above 3045 megawatts in the early evening of 8th February (at 6 pm Eastern Australian Standard Time). That was 340 megawatts lower than the all time South Australian peak of 3385 megawatts for South Australia on the 31st January 2011. The peak on February 8th was accompanied by a spot price of $13160/MWhour.

With the closure of Northern, any comparison with previous peak demand events should factor in any demand previously served by Northern Power Station. Before its closure Northern contributed around 420 megawatts power on average over the summer months. Without that supply available this year, the February 8th peak effectively exceeded the previous peak by around 80 megawatts in adjusted terms.

Queensland has experienced a hot summer with the maximum daily temperature in Brisbane reaching 37C for the first time since 2014 years, and an average daily maximum of 31.2C (at the time of writing). That is about one degree above the average of recent years. However, with only four days with a maximum temperature above 35C, compared to five in the summer of 2015, weather effects seem unlikely to fully account for the extraordinary rise in spot prices this summer.

In detail the Queensland market differs from other regions in the NEM in as much as it is the only region to have experienced significant demand growth in recent years. Mapping the change of demand growth over the years, by time of day, helps reveal the drivers for market tightening, as shown below firstly in absolute terms, and then in relative terms normalised against 2014.

Between 2009 and 2014, summer demand fell by about 400 megawatts (or 6%), with the greatest change occurring in the middle of day. This pattern is akin to the signal in South Australia shown above, and reflects how the growing deplyment of domestic rooftop PV was revealed to the market as a demand reduction.

Since, 2014 demand has grown appreciably across all times of day, skewed somewhat towards the evening. Relative to 2014, demand is up by almost 800 megawatts across the board, and by as much as 1200 megawatts at 9 pm. The 800 megawatt base shift in demand can be attributed in large part to new industrial loads associated with the commissioning of the LNG export gas processing facilities at Curtis Island.

In terms of extreme events, it is notable that February 12th this year set a new Queensland demand record at 5.30 pm of 9368 megawatts (at the half hour settlement period) with a spot price of $9005. This is extraordinary given it was a Sunday, a day which normally sees demand down several percentage points, on corresponding weekdays with similar temperature conditions.

Victoria is the exception to the trend of rising spot prices, with the summer prices of 2017 not much above long term average. In part, the relatively subdued prices can be attributed to the absence of extreme heat in southern Victoria so far this summer. The mean maximum daily summer temperature in Melbourne stands at about 27C, slightly below average of the previous five years. So far there have been no days with temperatures above 40C, compared to eight in 2014 and four in 2016.

The dominant factor in subduing the Victorian markets prices is likely to be the ongoing fall in demand. In the year to 18th February, demand in Victoria fell by 200 MW. This follows a persistent reduction in demand that has seen a fall of almost 500 megawatts over the last three years, equivalent to 9% of average demand. As shown below, the contrast with Queensland is stark, and reflects significant reductions in industrial demand stemming from the closure of the Point Henry aluminium smelter in August 2014 (Point Henry consumed up to 360 megawatts) and more recently the reduced demand from the Portland smelter on the back of damage caused by an unscheduled power outage on December 1st, 2016. While power capacity in Victoria was reduced by the closure of the 150 megawatt Anglesea coal-fired power plant in August 2015, the cumulative demand reduction over the last decade has led to substantial capacity overhang. All that is set to change with the closure of the 1600 Megawatt Hazelwood power station, slated for the end of March.

The figures shown in the previous sections reveal that peak demand events are stretching the power capacity of the NEM in unprecedented ways, for a variety of reasons. The tightening in the demand-supply balance is driving steep price rises that, if sustained, will have widespread repercussions. For example, a $20/MWhour rise in the Queensland spot price translates to a notional annual market value of $1 billion, that must eventually flow through the contract markets. With summer prices already more than $100/MWhour above last year, the additional costs to be passed onto energy consumers may well tally in the many billions of dollars.

In South Australia, the market tightening follows substantially the reduced supply stemming from the closure of the Northern Power Station.

In Queensland, the market tightening is being driven substantially by industrial loads such as the new LNG gas processing facilities. To the extent that the LNG industry is a significant driver, it is a heavy excise to pay for the privilege of exporting our gas resource. The makings for a policy nightmare, should the royalties from our LNG export be outweighed by the cumulative cost impacts passed on via our electricity markets.

It is important to note that the electricity market is designed so that prices fluctuate significantly in response to the normal capacity cycle, as capacity is added to or removed from the market following rises and falls in demand. In small markets, such as South Australia, the spot price fluctuations over the capacity cycle can be extreme, because the capacity of an individual large power plants can represent a large proportion of the native demand.

Although not large in terms of total capacity by Australian standards, Northerns 520 megawatt power rating represented around 40% of the South Australias median demand. That made Northern one of the Australias most significant power stations in terms of its regional basis size. Its withdrawal has dramatically and abruptly reduced the capacity overhang in South Australia. Spot prices were always going to rise as a consequence, because that is the way the market was designed. In addition, Northerns closure has also increased South Australias reliance on gas generation, and it has concentrated market power in the hands of remaining generators, both of which have had additional price impacts beyond the normal market tightening.

In both Queensland and South Australia, the rises in spot prices is signalling the growing tightness in the market. Under normal circumstances would serve to drive investment in new capacity. The lessons of Northern show that any new capacity in South Australia will need to be responsive to the changing pattern of demand, unless the makers rules are changed.

Further, both regions have questions about the adequacy of competition. Both are subject to the impacts of parallel developments in the gas markets, which have made gas production much more expensive. In the case of Queensland this is greatly exacerbated by the extra demand from the LNG gas production facilities.

Finally, these insights have importance for predicting how the markets the will react to the impending close of the 1600 MW Hazelwood Power Station in Victoria, all topics I hope to consider in following posts in this series.

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Anatomy of an energy crisis – a pictorial guide to the tightening market, Part 2 – The Conversation AU

Recommendation and review posted by Guinevere Smith

Stem Cell therapy is future of anti-ageing – Bangalore Mirror

Posted: February 20, 2017 at 5:41 am

Chronological aging shows the natural life cycle of the cells as opposed to cells that have been unnaturally replicated multiple times or otherwise manipulated in a lab.

In order to preserve the cells in their natural state, Penn researchers developed a system to collect and store them without manipulating them, making them available for this study. They found stem cells collected directly from human fat — called adipose-derived stem cells (ASCs) — can make more proteins than originally thought. This gives them the ability to replicate and maintain their stability, a finding that held true in cells collected from patients of all ages.

Our study shows these cells are very robust, even when they are collected from older patients, said Ivona Percec, MD, director of Basic Science Research in the Center for Human Appearance and the studys lead author. It also shows these cells can be potentially used safely in the future, because they require minimal manipulation and maintenance.

Stem cells are currently used in a variety of anti-aging treatments and are commonly collected from a variety of tissues. But Percecs team specifically found ASCs to be more stable than other cells, a finding that can potentially open the door to new therapies for the prevention and treatment of aging-related diseases.

Unlike other adult human stem cells, the rate at which these ASCs multiply stays consistent with age, Percec said.

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Stem Cell therapy is future of anti-ageing – Bangalore Mirror

Recommendation and review posted by Guinevere Smith

Excellent weapon in war on aging – Palm Beach Post

Posted: February 20, 2017 at 5:41 am

Question: What is the latest skin tightening technology?

Answer: Ultherapy is a treatment based on ultrasound technology. It works by using ultrasound-guided technology to actually view the underlying tissue that is being treated.

We are able to reach below the dermal layer, sending ultrasound energy penetrating deeper to the fibro-muscular tissue, promoting collagen production. If you have weakened collagen in the deeper connective tissue, it can cause the skin to become prone to gravitational forces and begins to stretch, sag and shift downward a process we call aging.

This is where Ultherapy plays a role. It is FDA approved for the forehead, face and neck.

The Ultherapy treatment begins with marking the area on the face to be treated. This is the same target area that is addressed in cosmetic surgery for skin tightening.

Once the skin is marked for treatment, a mild sedative is given. A full face treatment can take anywhere from 45 to 60 minutes. You may return to normal activities and can experience flushing or redness that should resolve within a few hours.

The regenerative process is initiated at the first treatment, however, results may take up to six months since you are relying on the bodys own healing process to repair and rebuild your skins foundation.

For more information, visitwww.MDBeautyLabs.com, or call (561) 655-6325 to schedule a complimentary consultation.

Daniela Dadurian, M.D., specializes in anti-aging medicine and is an expert in non-surgical body-contouring techniques. She received her medical degree from the University of Miami School of Medicine and has traveled the world researching the safest and latest technologies on the market.

______________________________________

MD Beauty Labs Medical Spa and Wellness Center

320 S. Quadrille Blvd. West Palm Beach

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Excellent weapon in war on aging – Palm Beach Post

Recommendation and review posted by Guinevere Smith

Lonza to Manufacture Selecta Gene Therapy Candidate for MMA – Genetic Engineering & Biotechnology News

Posted: February 18, 2017 at 9:48 pm

Lonzas viral-based therapeutics unit Lonza Houston has agreed to manufacture an Anc80-AAVbased gene therapy product for Selecta Biosciences proprietary program for the treatment of methylmalonic acidemia (MMA) and may produce other Anc80-based products for which Selecta holds exclusive options, the companies said today.

The companies said their strategic manufacturing agreementwhose value was not disclosedwill apply to Selectas program Lonzas expertise in developing robust and industry-scale manufacturing platforms for viral-based products.

Lonza will utilize our extensive cGMP manufacturing knowledge and world-class quality systems to help Selecta Biosciences develop promising novel therapeutics for patients impacted by MMA and other devastating diseases, Andreas Weiler, Ph.D., head of the Emerging Technologies Business Unit for Lonzas Pharma & Biotech segment, said in a statement.

Anc80-AAV, an in silico-designed synthetic gene therapy vector, has generated preclinical data suggesting its potential to provide what the companies termed superior gene expression levels in the retina, liver, muscle, cochleas outer hair cells, and other tissue targets. Anc80-AAV has also shown reduced cross-reactivity compared to naturally occurring adeno-associated viral vectors (AAVs) now in clinical development, Lonza and Selecta said.

Selecta exclusively licensed Anc80 for MMA from Massachusetts Eye and Ear (MEE) in May 2016. The vector was developed by the laboratory of Luk H. Vandenberghe, Ph.D., director of MEEs Grousbeck Gene Therapy Center and an assistant professor at Harvard Medical School. Under the license agreement, whose value was not disclosed, Selecta also has the exclusive option to develop gene therapies using Anc80 for additional predefined lysosomal storage, genetic muscular, and genetic metabolic diseases.

Selecta focuses on combining novel and proprietary viral vectors with its immune tolerance Synthetic Vaccine Particles (SVP) to enable the first nonimmunogenic gene therapies, providing the potential for repeat dosing.

Selecta said it intends to combine Anc80 with recently discovered transgenes and Selectas SVP-Rapamycin to create a novel gene therapy candidate for MMA. The candidate will be designed to enable treatment of patients with and without pre-existing anti-AAV antibodies, prevent cellular immune responses that often reduce the expression levels of gene therapies, and provide the ability to administer repeat gene therapy doses to achieve sufficient levels of methylmalonyl-CoA mutase, the enzyme that MMA patients lack.

To advance the MMA program, Selecta last year entered into a Collaborative Research and Development Agreement (CRADA) with MEE and the NIHs National Human Genome Research Institute. The CRADAs principal investigators are Dr. Vandenberghe and Charles Venditti, M.D., Ph.D., senior investigator and head, Organic Acid Research Section, Medical Genomics and Metabolic Genetics Branch.

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Lonza to Manufacture Selecta Gene Therapy Candidate for MMA – Genetic Engineering & Biotechnology News

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