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2013-10-04

Certain type of fat could help humans lose weight

Oct. 2, 2013 — A diet high in a certain type of fat may actually increase metabolism, according to recent research by Texas Tech University nutrition scientists.

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After studying genetically modified mice, the discovery could lead to supplements and a diet regime that will increase metabolism and decrease muscle fatigue in humans. The research was published in the peer reviewed journal, The Journal of Lipid Research.

Chad Paton, an assistant professor of nutritional biochemistry in the Department of Nutrition, Hospitality and Retailing, said he and colleagues were curious why skeletal muscles of obese people contained a certain type of enzyme that breaks down saturated fats. To test what that enzyme did, Paton's lab and colleagues from the University of Wisconsin -- Madison genetically modified mice so that their muscles would constantly produce the enzyme.

"We used a transgenic mouse model, and we took the gene that makes the enzyme that's not normally expressed and took away it's regulation to make it active all the time," Paton said. "What we found in those animals is they had a hypermetabolic rate compared to the wild mice, increased energy consumption and greatly increased these animals' exercise capacity."

The enzyme, called SCD1, converts saturated fat into monounsaturated fat, which is easier to metabolize. The liver will produce this enzyme depending on the fat content of the food consumed, he said. Fatty adipose tissue produces it all the time as a way of regulating itself.

Only in heavily exercised muscle tissue or in the case of obesity does skeletal muscle produce the enzyme, he said.

After looking at skeletal muscles of the genetically modified mice compared to that of the wild mice, Paton and his team discovered higher levels of polyunsaturated fats, particularly linoleic acid, gotten only through diet.

Higher levels of linoleic acid could only mean one thing -- the modified mice were eating more food. But Paton's team found that the modified mice weighed less than the wild mice. On top of that, their ability to exercise increased.

"We found in the genetically modified animals that they had a hypermetabolic rate," he said. "They were increasing their energy consumption, and they experienced greatly increased exercise capacity. For example, on the exercise wheels, normal mice fatigue after 7 to 10 minutes. These genetically modified animals wouldn't fatigue for about 70 minutes. So they were running a lot longer. Sedentary mice looked more like exercise-trained mice. That really made us look in a lot more detail what was happening in the skeletal muscle." By looking at the muscle tissues, Paton and his team members discovered a trend.

More of the SCD1 enzyme and a greater appetite by the mice meant more linoleic acid in the tissues. The linoleic acid switched on part of the muscle cell's DNA that encouraged the cells to make more mitochondria and to turn on a protein that encouraged the cell to burn off excess energy from the extra food as heat -- a process called uncoupling.

Humans store unused energy as fat, Paton said. And while that helped our ancestors survive, it can lead to obesity for some people in today's world of plentiful food.

While genetically modifying humans isn't an option, Paton said this experiment could hold useful information for supplementing human diets to achieve the same results.

"That's where we have taken our research from this," he said. "You can't change the human genome, but that gives us insight if you could activate the same part of the DNA in human in skeletal muscles that burn off excess energy as heat instead of storing it. Perhaps it's a supplement people could take that will turn on the cells' metabolic machinery burn off energy and increase mitochondria."

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Sieving through 'junk' DNA reveals disease-causing genetic mutations

The new method designed by the team, described in the journal Science, identified these variants in the under-explored regions of DNA that do not code for proteins, but instead influence activity of other genes. As even more whole genome sequences become available, this approach can be applied to find any potential disease-causing variant in the non-coding regions of the genome.

Researchers can now identify DNA regions within non-coding DNA, the major part of the genome that is not translated into a protein, where mutations can cause diseases such as cancer.

Their approach reveals many potential genetic variants within non-coding DNA that drive the development of a variety of different cancers. This approach has great potential to find other disease-causing variants.

Unlike the coding region of the genome where our 23,000 protein-coding genes lie, the non-coding region -- which makes up 98% of our genome -- is poorly understood. Recent studies have emphasised the biological value of the non-coding regions, previously considered 'junk' DNA, in the regulation of proteins. This new information provides a starting point for researchers to sieve through the non-coding regions and identify the most functionally important regions.

"Our technique allows scientists to focus in on the most functionally important parts of the non-coding regions of the genome," says Professor Mark Gerstein, senior author from the University of Yale. "This is not just beneficial for cancer research, but can be extended to other genetic diseases too."

The team used the full set of genetic variants from the first phase of the 1000 Genomes Project, together with information about the non-coding regions generated by the ENCODE Project, and identified regions that did not accumulate much variation.

Protein-coding genes play a crucial role in human survival and fitness, and are under strong 'purifying' selection, which removes variation. The team found that some non-coding DNA regions showed almost the same low levels of variation as protein-coding genes, and called these 'ultrasensitive' regions.

Within the ultrasensitive regions, they looked at specific single DNA letters that, when altered, caused the greatest disturbance to the genetic region. If this non-coding, ultrasensitive region is central to a network of many related genes, variation can cause a greater knock-on effect, resulting in disease.

They integrated all this information to develop a computer workflow known as FunSeq. This system prioritises genetic variants in the non-coding regions based on their predicted impact on human disease.

"Our method is a practical and successful way to screen for purifying selection in non-coding regions of the genome using freely available data such as those from the ENCODE and 1000 Genomes Projects," says Dr Yali Xue, author from the Wellcome Trust Sanger Institute. "It really shows the value of these large-scale open access data-sets."

The team applied FunSeq to 90 cancer genomes including breast cancer, prostate cancer and brain tumours, and found nearly 100 potential non-coding cancer driving variants. In the breast cancer genomes, for example, they found a single DNA letter change that seems to have great impact on the development of breast cancer. This single letter change occurs in an ultrasensitive region that is central to a network of many related genes.

"Although we see that the first effective use of our tool is for cancer genomes, this method can be applied to find any potential disease-causing variant in the non-coding regions of the genome," says Dr Chris Tyler-Smith, lead author from the Wellcome Trust Sanger Institute. "We are excited about the vast potential of this method to find further disease-causing, and also beneficial variants, in these crucial but unexplored areas of our genome."

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3-D printing: The greener choice

Even Pearce, an aficionado of the make-it-yourself-and-save technology, was surprised at his study's results. It showed that making stuff on a 3D printer uses less energy -- and therefore releases less carbon dioxide -- than producing it en masse in a factory and shipping it to a warehouse.

Most 3D printers for home use, like the RepRap used in this study, are about the size of microwave ovens. They work by melting filament, usually plastic, and depositing it layer by layer in a specific pattern. Free designs for thousands of products are available from outlets like Thingiverse.com.

Common sense would suggest that mass-producing plastic widgets would take less energy per unit than making them one at a time on a 3D printer. Or, as Pearce says, "It's more efficient to melt things in a cauldron than in a test tube." However, his group found it's actually greener to make stuff at home.

They conducted life cycle impact analyses on three products: an orange juicer, a children's building block and a waterspout. The cradle-to-gate analysis of energy use went from raw material extraction to one of two endpoints: entry into the US for an item manufactured overseas or printing it a home on a 3D printer.

Pearce's group found that making the items on a basic 3D printer took from 41 percent to 64 percent less energy than making them in a factory and shipping them to the US.

Some of the savings come from using less raw material. "Children's blocks are normally made of solid wood or plastic," said Pearce, an associate professor of materials science and engineering/electrical and computer engineering. 3D printed blocks can be made partially or even completely hollow, requiring much less plastic.

Pearce's team ran their analysis with two common types of plastic filament used in 3D printing, including polylactic acid (PLA). PLA is made from renewable resources, such as cornstarch, making it a greener alternative to petroleum-based plastics. The team also did a separate analysis on products made using solar-powered 3D printers, which drove down the environmental impact even further.

"The bottom line is, we can get substantial reductions in energy and CO2 emissions from making things at home," Pearce said. "And the home manufacturer would be motivated to do the right thing and use less energy, because it costs so much less to make things on a 3D printer than to buy them off the shelf or on the Internet."

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Passives CK smoke detector switches meet EN-14604

2013/10/03

CK560 switches for Smoke Detectors C&K Components has expanded its line of switch products for smoke detectors in support of the new European EN-14604 standard.

“According to the new regulation, all smoke detectors sold in the European Union must include the CE marking and comply with EN-14604 standards, which require all smoke detectors to be equipped with a test button,” said the firm.

The most compact EN-14604-compliant switch is the KMT0 series. “Moreover, the IP68-rated switch’s ability to withstand gas corrosion tests makes it the ideal solution for harsh environment applications,” claimed C&K.

These have a 0.65mm profile and an operating life of up to one million cycles. An ultra-low current version is available to extend battery life.

Top- or side-actuated KSA/KSC Series sealed tactile switches have customisable actuation and button height. Sealing is IP67, contacts are gold, and operating life is up to one million cycles.

“Another switch product that meets the requirements for smoke/fire detectors and carbon monoxide detectors is the KSE Series of low-profile tactile switches,” said the firm. Sealing is, again, IP67.

Miniature low-profile RTE rotary DIP switches are also suitable, and available in surface mount and through-hole models. There are SPDT, SP3T and SP4T, as well as binary-decimal and hexa-decimal coding. The cover is stainless steel and predicted life is up to 20,000 actuations.

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Physicists 'entangle' microscopic drum's beat with electrical signals

Oct. 3, 2013 — Extending evidence of quantum behavior farther into the large-scale world of everyday life, physicists at the National Institute of Standards and Technology (NIST) have "entangled" -- linked the properties of -- a microscopic mechanical drum with electrical signals.

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The results confirm that NIST's micro-drum could be used as a quantum memory in future quantum computers, which would harness the rules of quantum physics to solve important problems that are intractable today. The work also marks the first-ever entanglement of a macroscopic oscillator, expanding the range of practical uses of the drum.

Entanglement is a curious feature of the quantum world once believed to occur only at atomic and smaller scales. In recent years, scientists have been finding it in larger systems. Entanglement has technological uses. For instance, it is essential for quantum computing operations such as correcting errors, and for quantum teleportation of data from one place to another.

The experiments, described Oct. 3, 2013, in Science Express, were performed at JILA, a joint institute of NIST and the University of Colorado Boulder.

NIST introduced the aluminum micro-drum in 2011 and earlier this year suggested it might be able to store data in quantum computers. The drum -- just 15 micrometers in diameter and 100 nanometers thick -- features both mechanical properties (such as vibrations) and quantum properties (such as the ability to store and transfer individual quanta of energy).

The drum is part of an electromechanical circuit that can exchange certain quantum states between the waveform of a microwave pulse and vibration in the drum. In the latest JILA experiment, a microwave signal "cooled" the drum to a very low energy level, just one unit of vibration, in a way analogous to some laser-cooling techniques. Then another signal caused the drum's motion to become entangled with a microwave pulse that emerged spontaneously in the system.

The drum stored the quantum information in the form of vibrational energy for at least 10 microseconds, long enough to be useful in experiments. Then the same type of microwave signal that cooled the drum was used to transfer the state stored in the drum to a second microwave pulse.

Researchers measured the properties of the two microwave pulses -- specific points on the curves of the travelling waves -- and found that the results were strongly correlated over 10,000 repetitions of the experiment. The evidence of quantum entanglement comes from the fact that measuring the first microwave pulse allowed scientists to anticipate the characteristics of the second pulse with greater accuracy than would otherwise be expected. The correlations between the two pulses indicated that the first pulse was entangled with the drum and the second pulse encoded the drum's quantum state.

The results suggest that the drum, in addition to its potential as a quantum memory device, also could be used to generate entanglement in microwaves, to convert one form of quantum information to an otherwise incompatible form, and to sense tiny forces with improved precision.

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Business IEF2013: Compound Semis are the future, says IQE

2013/10/03

Mixing compound semiconductor materials with CMOS is the way ahead for the IC industry as it struggles to get increased performance from scaling.

Untitled This was the message to this morning’s IEF 2013 meeting in Dublin from Drew Nelson, CEO of compound semiconductor wafer producer IQE.

“There’s been a feeling that compound semiconductors are a niche part of the semiconductor industry which should be crushed at every opportunity,” joked Nelson, pointing out that compound semiconductors were key to most forms of connectivity.

IQE has increased sales 10x over the last ten years. Nelson believes it can grow 10x over the next ten years as combinations of compound semiconductors and silicon allow Moore’s Law to continue in one form or another.

“The material properties of compound semiconductors are so much better than silicon,” said Nelson, “all have huge advantages over silicon. Growing InGaAs quantum wells on silicon delivers a 30x improvement over silicon.”

With Intel, IQE has developed a narrow fin-width 3-D Tri-gate InGaAs QWFET with the steepest sub-threshold swing and smallest DIBL ever reported for any high-K III-V FET.

IQE has also had significant successes with III-V growths on Ge-coated Si templates, said Nelson, but these results are secret.

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2013-10-03

Embedded Systems FreeRTOS gets lightweight IoT interface with Nabto

2013/10/03

FreeRTOS has been given Internet-of-Things (IoT) capability, in less than 23kbyte on a microcontroller.

This is not much memory as serving web pages from a device generally requires it to run a TCP/IP stack and have some form of file system.

The key to delivering web pages from such a small footprint is to shift heavy user-interface processing to the PC or smartphone that is reading or controlling the remote IoT-enabled device, using a cloud-based system called Nabto, from a Danish firm of the same name.

“FreeRTOS plus Nabto is a small, less than 23Kb including IP stack, piece of C code that, when integrated into an embedded networked device, allows that device to be remotely accessed and controlled through a web based interface or intelligent data acquisition system,” said Real Time Sytems, the company that supports FreeRTOS.

With Nabto, the IoT device only handles a small amount of data – out-going data from its sensors and in-coming commands. The remainder of any web pages seen by the user is served by a remote server in the cloud.

Page seen by the user are assembled from the two sources in the PC or phone by a Nabto plug-in in its web browser,.

“Our technology enables the client to read the device from anywhere, just like Skype,” Nabto founder and CEO Carsten Gregersen told Electronics Weekly. “Security is built in, similar to SSL or TLS security.”

“The plug-in is doing the clever bit,” added Richard Barry, the man behind FreeRTOS. “It will run with any browser. The first time you try to connect to embedded device, it will ask you to install the plug-in, only the first time, the cloud resolves the address for you.”

In use, the plug-in goes first to the cloud server. “The server knows where both items are and serves a specification file to generate a web server interface, mediating direct connection to the device,” said Barry. “It is all seemless to the user. The external device can work behind firewall, doesn’t need a file system, and doesn’t need TCP/IP stack.”

Companies selling devices with FreeRTOS and Nabto, like a room thermostat for example, would have a URL, like BrownsThermostat.com, and each individual product would have a unique address built-in: 456.brownsthermostat.com, for example.

For development, and for use across a local network – for example in a factory – no cloud server is needed. Instead the web content is cached on the user’s PC or phone. “If local, the plug-in will just search and come up with a list of devices to connect to,” said Bary.

Writing apps is simple, claims Barry. “If you can write web pages, you can write apps. The developer just has to build code into the application, just one C function. They don’t have to know how networks work,” he said. There are two application examples on the FreeRTOS website.

In commercial use, capacity would be rented on the cloud server, or “you can buy the server software and host it yourself,” said Barry. “To start, you don’t need to pay anyone, just run it locally.”

There is a lot more on the Nabto page of the FreeRTOS site.

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Business IEF2013: Wafer cost to soar after 28nm, says TSMC

2013/10/03

Dismaying the IEF2013 meeting in Dublin this morning was a foil put up by TSMC senior director for R&D, Yee-Chaung See, that showed a steeply rising wafer cost after the 28nm node.

So steep was the anticipated cost curve that the prospective cost of a 10nm wafer appeared to be about 4x the cost of a 28nm wafer.

Asked if this was a show-stopper for the industry, Yee-Chuang replied: “We need msny innovations to bring the cost down.”

The two most important innovations to achieve this are 450mm and EUV.

“Progress towards 250W source power EUV must not slow down,” said Yee-Chuang, adding that he expected to see it by 2015.

However only around 10W is currently being achieved, although Gigaphoton of Japan recently announced a 15W power source.

On the spreading TSMC ecosystem, Yee-Chuang noted that the TSMC ‘grand Alliance’ now spends a cumulative $12 billion on R&D – more than any IDM. Itnel spends abot $10 billion a year on R&D.

Another sign of the growing power of the TSMC ecosystem is that the company currently employs “close to” 1,000 design engineers, said Yee-Chuang.

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Insect repellent: Scientists find insect DEET receptors, develop safe alternatives to DEET

Now researchers at the University of California, Riverside have identified these DEET-detecting olfactory receptors that cause the repellency -- a major breakthrough in the field of olfaction.

Further, the team of researchers has identified three safe compounds that mimic DEET and could one day be used to prevent the transmission of deadly vector-borne diseases such as malaria, dengue, West Nile virus, and yellow fever.

Study results appear online Oct. 2 in Nature.

"Until now, no one had a clue about which olfactory receptor insects used to avoid DEET," said Anandasankar Ray, an associate professor of entomology, who led the research team. "Without the receptors, it is impossible to apply modern technology to design new repellents to improve upon DEET."

The method Ray's team used to identify the receptors examined in an unbiased fashion all the sensory neurons in the insect, which was the key to successfully finding them. In their experiments, the researchers used the genetic model system Drosophila melanogaster (fruit fly) that was genetically engineered in such a way that neurons activated by DEET glowed fluorescent green. The researchers thus found the receptors, called Ir40a receptors, lining the inside of a poorly studied region of the antenna called the sacculus.

Introduced in the 1940s, DEET has remained unchanged for the past 65 years largely because the receptor in insects for DEET was unknown. Capable of dissolving plastics and nylon, DEET has been reported to inhibit an enzyme (acetylcholinesterase) in mammals that is important in the nervous system. DEET is also unaffordable and inconvenient for use in Africa and other parts of the world where hundreds of millions of people suffer from insect-transmitted diseases.

"Our three compounds, which we tested rigorously in the lab, do not dissolve plastics," Ray said. "They are approved by the Food and Drug Administration for consumption as flavors or fragrances, and are already being used as flavoring agents in some foods. But now they can be applied to bed-nets, clothes, curtains -- making them ward off insects."

Using novel chemical informatics strategies, Ray's lab screened half a million compounds against the DEET receptor to identify substitutes. A computer algorithm the team developed identified which compounds are not only predicted to be strong repellents but also found naturally in fruits, plants or animals. The algorithm predicted nearly 200 natural DEET substitutes; of which the researchers tested ten compounds. Of these, eight were strong repellents on flies, of which four were tested in Aedes mosquitoes and found to be strong repellents. Of the four compounds, three are already approved by the Food and Drug Administration as food additives.

"All three compounds activated the same antennal cells in flies as DEET," Ray said. "What's really encouraging is that some of these compounds may be affordable to produce in large quantities. In the future, using this algorithm, we could find chemicals that activate DEET receptors but are substantially different, with far better properties than DEET. We could find truly novel repellants that have remarkable properties such as large spatial protection and long-term protection."

With the help of UC Riverside's Office of Technology Commercialization (OTC), Ray is exploring options for commercializing the technology. OTC has already filed two patents on the research.

"We think there is incredible potential for a start-up company to develop new repellents based on Dr. Ray's current research," said Michael Pazzani, the vice chancellor for research and economic development at UCR. "In past work, his lab identified compounds that mask the host from insects, as well as compounds that serve as lures. The lab's new research has given us compounds that serve as repellents, making possible safe alternatives to DEET for a variety of applications including control of mosquitoes, flies, and possibly lice, bed bugs, ants, cockroaches, grain pests and agricultural pests."

When commercialized, the findings by Ray's team could have wide applications.

"Ir40a and its related proteins are conserved not only in flies and mosquitoes, but also in many other insects that are human and plant pests," Ray explained. "Our findings could lead to a new generation of cheap, affordable repellents that could protect humans, animals and, in the future, our crops as well."

He was joined in the study by UCR's Pinky Kain (co-first author who found the receptor), former graduate student Sean Michael Boyle (co-first author who identified the substitutes), Sana Khalid Tharadra, Tom Guda, Christine Pham, and Anupama Dahanukar.

The three natural compounds, identified by Ray's group, that mimic DEET are methyl N,N-dimethyl anthranilate, ethyl anthranilate and butyl anthranilate. (More than a hundred compounds still await testing in Ray's lab.)

The research was partially supported by the National Institutes of Health's National Institute of Allergy and Infectious Diseases (grants R56AI099778 and R01AI087785) and the National Institute of Neurological Disorders and Stroke (grant R21NS074332) and internal funding from UCR.

Second study

In a separate study published Oct. 1 in the journal e-Life, Ray's group discusses a computational method, developed by Boyle, for screening thousands of chemicals and predicting which odorants -- or odor molecules -- will interact with specific odorant receptors. This research, too, may lead to the development of more effective insect repellents.

Specifically, the researchers used their computational approach to study the interactions between 24 odorant receptors in Drosophila antennae and 109 odorants. They then identified common structural features in the odorants and used this information to screen more than 240,000 different odorant-like volatile compounds. For each receptor, they came up with 500 new odorants that were predicted to interact most strongly with it. They then tested their predictions for some receptors on living flies and found that approximately 71 percent of the predicted compounds activated or inhibited the receptors.

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Recruiting E. coli to combat hard-to-treat bacterial infections

Oct. 2, 2013 — The notorious bacteria E. coli is best known for making people sick, but scientists have reprogrammed the microbe -- which also comes in harmless varieties -- to make it seek out and fight other disease-causing pathogens. The researchers' report appears in the journal ACS Synthetic Biology and describes development of this new type of E. coli that can even kill off slimy groups of bacteria called biofilms that are responsible for many hard-to-treat infections, such as those that take hold in the lungs, the bladder and on implanted medical devices.

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Matthew Wook Chang and colleagues explain that biofilm infections are difficult to treat because the bacteria hide away under a protective barrier of sugars, DNA and proteins. That shield makes them very resistant to conventional therapies. In addition, overuse of antibiotics in medicine and agriculture also have made some bacteria, such as MRSA, shrug off most known treatments, making at least 2 million Americans sick every year. This growing public health threat has motivated scientists to look for new antibiotics and alternative treatments to beat infections. In the past, researchers made bacteria that fight off other microbes, but they had limitations. Chang's team addressed those limitations by making a new kind of bacterial "gun-for-hire" that can sense an infection, swim toward it and kill off the disease-causing microbes.

They reprogrammed E. coli to sense Pseudomonas aeruginosa -- a bacteria that can form biofilms and causes hospital-acquired infections in the lungs and the gut. The new E. coli then swims directly toward P. aeruginosa and launches an attack with an antimicrobial peptide and an enzyme that breaks down biofilms. Though the researchers successfully tested their engineered microbe on P. aeruginosa, they say that their engineering strategy could be used to combat other pathogens as well.

The authors acknowledge funding from the National Medical Research Council of Singapore and the U.S. Defense Threat Reduction Agency.

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