The new breed of cutting-edge catalysts

 Advances in catalyst research could create a superhighway to clean energy sources and a more-sustainable chemical industry.

“Chemists are striving to build catalysts around cheaper, 'Earth-abundant' elements such as iron, nickel or copper.”

In her 1794 book, An Essay on Combustion, Scottish chemist Elizabeth Fulhame noted a peculiar fact: substances such as coal and charcoal burned better when they were damp. After many experiments to understand why, she concluded that the water briefly split into hydrogen and oxygen, which interacted with the other compounds in a way that made the combustion go faster. Yet at the end, Fulhame wrote, the process “forms a new quantity of water equal to that decomposed”.

Many historians consider this to be the first scientific account of a catalyst: a material that speeds reactions by making or breaking chemical bonds, without being consumed. It was hardly the last: modern chemistry would be almost inconceivable without catalysts. “They not only make transformations accessible, but also direct them in new ways,” says Susannah Scott, a chemist at the University of California, Santa Barbara. “That's very powerful.”

Catalysts are used in some 90% of processes in the chemical industry, and are essential for the production of fuels, plastics, drugs and fertilizers. At least 15 Nobel prizes have been awarded for work on catalysis. And thousands of chemists around the world are continually improving the catalysts they have and striving to invent new ones.

That work is partly driven by an interest in sustainability. The aim of catalysis is to direct reactions along precisely defined pathways so that chemists can skip reaction steps, reduce waste, minimize energy use and do more with less. And with growing concerns about climate change and the environment, sustainability has become increasingly important. Catalysis is a key principle of 'green chemistry': an industry-wide effort to prevent pollution before it happens.

Catalysts are also seen as the key to unlocking energy sources that are much more inert and difficult to use than coal, oil or gas, but much cleaner. Catalysis can make it more economically feasible to split water into oxygen and hydrogen fuel, or can open up new ways to use raw materials such as biomass or carbon dioxide. “These are feedstocks that are ripe for advances in catalysis,” says Melanie Sanford, a chemist at the University of Michigan in Ann Arbor.

These challenges have led to an explosion in catalyst innovation, with the annual number of publications on the subject tripling in the past decade. Many groups are coming up with new small-molecule complexes or are chemically tailoring biological enzymes in search of radically new catalytic activity. Others are pursuing advances in nanotechnology, which allow them to engineer the action of solid catalysts at the atomic scale. Still others are experimenting with catalysts that are activated by light, or that incorporate the DNA double helix. And everyone in the field is trying to streamline the search for better catalysts with modern computational modelling tools.

The pace of innovation is such that even the experts are struggling to keep up, says Scott, who leads the US Department of Energy's efforts to develop benchmarks for the new catalysts' performance¹. “We need to make sure we are advancing the science that's most efficient,” she says.

And the scope of catalysis is increasing rapidly. “Twenty years ago,” says John Hartwig, a chemist at the University of California, Berkeley, “catalysis to make molecules that were complex did not exist.” Anyone who wanted to modify a large complicated structure would have to tear it down and build it back up, says Sanford. But now, chemists can often edit parts of a molecule precisely. “It's incredibly enabling,” she says.

Cut-price catalysts

Using a catalyst is like bulldozing a shortcut between reactants A and product B, bypassing convoluted chemical pathways that might otherwise take forever. Using a really good catalyst is like building a multilane superhighway. And some of the best are the 'homogeneous' catalysts: free-floating molecules that are mixed in with the reactants.

Industrial catalysts in this category most often consist of a metal ion that does the hard work of making or breaking chemical bonds, surrounded by 'ligands': connected groups, often carbon-based, that control the reactants' access to the ion. Much of the research in this field comes down to tailoring these ligands to produce a catalyst that performs only a desired reaction.

Unfortunately, many of the successes so far have come through the use of scarce and expensive metals such as palladium, platinum, ruthenium and iridium. Today, chemists are increasingly striving to build catalysts around cheaper, 'Earth-abundant' elements such as iron, nickel or copper — or to do without metals altogether.

Nickel is a particularly attractive candidate for mimicking the chemistry of palladium and platinum because it sits directly above them in the periodic table, and therefore has similar properties. At the Swiss Federal Institute of Technology in Lausanne, for example, synthetic chemist Xile Hu and his group are working with a remarkably versatile nickel complex² that they first reported in 2008. The complex consists of a nickel ion surrounded by a single, large ligand that binds to it in three places, leaving a fourth binding spot available for catalysing reactions. A similar ligand is already used in certain palladium catalysts. But the radius of a nickel ion is almost 20% smaller than that of a palladium ion, so Hu had to shrink the ligand to fit it more closely around the nickel. To do so, he replaced phosphorus atoms in the ligand with smaller nitrogen ones.

The result is a rigid ligand that stabilizes the nickel ion as it performs a wide array of reactions^3, 4, 5. The original nickel catalyst is already available commercially, and Hu is systematically modifying the ligand to make a whole family of catalysts.

In 2008, chemists discovered that certain standard catalysts could be made more powerful by combining them with a technique known as photoredox catalysis. When photoredox catalysts absorb light, an electron leaps from the metal ion to the ligand and becomes stuck there, leaving the molecule in an unstable state. “The catalyst becomes desperate to fill the hole in the metal and get rid of the electron in the ligand,” explains David MacMillan, a chemist at Princeton University in New Jersey who first reported⁶ the idea in collaboration with chemist David Nicewicz from the University of North Carolina at Chapel Hill. But the only way the photoredox system can accomplish this is to trade electrons with the standard catalyst, supercharging it and triggering chemical transformations that were previously impossible. As a bonus, the photoredox catalysis drives the process with energy that it absorbed from light, reducing the heat required to keep the reaction going.

Nicewicz and MacMillan have independently used photoredox catalysis to make major improvements to the Buchwald–Hartwig reaction, which is frequently used to bond carbon with nitrogen when making drugs. Typically, the reaction requires the use of palladium salts, expensive, phosphorus-based ligands and difficult-to-make reactants. But in 2015, Nicewicz's group announced⁷ that it had not only made a carbon–nitrogen bond using a completely metal-free catalyst, but had done so starting from cheaper and more accessible reactants; it is already being used by pharmaceutical companies, says Nicewicz. In June, MacMillan's group and its collaborators at Merck Research Laboratories in Rahway, New Jersey, reported⁸ making the Buchwald–Hartwig reaction work with minute amounts of an iridium light absorber and a nickel salt, eliminating the need for ligands.

A specific challenge for many researchers is to find better ways of creating the carbon–fluorine bonds at the heart of fluorinated compounds that are widely used in pharmaceuticals, agrochemicals and medical imaging. Currently, the bonds are made using expensive specialized reagents or the highly corrosive gas hydrogen fluoride. In 2013, a team of researchers led by Sanford showed⁹ how to make such bonds with a safer potassium fluoride salt using a copper catalyst. First, the catalyst is exposed to a compound that strips away three of its electrons. This leaves the catalyst so hungry for electrons that it can pull some from a nearby fluoride ion, which holds them in a notoriously tight grip. The fluoride is then so desperate for a replacement electron that it will readily bind with a carbon atom to get it.

Pebbles in a stream

Despite their versatility, many homogeneous catalysts are fragile. Their internal bonds weaken after prolonged exposure to heat and collisions with reactant molecules, and their ligands start disintegrating. “They die after a while,” says Sanford.

That is a big reason why large-scale industry tends to use 'heterogeneous' catalysts: solid materials that are fixed in place while the reactants stream past. A classic example is the mix of powderedplatinum and other metals found in the catalytic converters that clean vehicle exhaust gases. In the past, chemists had a tough time designing heterogeneous catalysts with atomic precision because it was difficult to make and study the active sites, where catalysis occurs, in a solid material. Mostly they had to optimize the catalysts through trial and error. But what's changing, says Scott, “is the synthetic control that we can exert over the materials”. In particular, rapid advances in nanotechnology are allowing chemists to work towards systems with the robustness of solid catalysts and the high performance of homogeneous ones.

At the Chinese Academy of Sciences' State Key Laboratory of Catalysis in Dalian, director Can Li has used platinum and cobalt oxide nanoparticles to create a catalyst for splitting water with sunlight¹⁰ (see 'Light splitter'). He starts by sticking the nanoparticles to crystals of a semiconductor called bismuth vanadium oxide, with each type of particle carefully isolated on a specific face of each crystal. Then, when he immerses the crystals in water and exposes them to light, photons strike the semiconductor and loosen electrons. The result is a flow of current that the nanoparticles use to break water molecules into hydrogen and oxygen. Oxygen gas comes bubbling off the cobalt oxide sites, while positively charged hydrogen ions migrate to the platinum particles. “We separated the active sites to block the reverse reaction,” says Li — that is, a dangerously explosive conversion of hydrogen and oxygen back into water. (To simplify the experimental set-up, the hydrogen ions are currently captured by a separate compound rather than turned into gas.) The process is not yet efficient enough to be economically viable, says Li. But his team is testing combinations of semiconductors and metal catalysts to refine the design.

Audrey Moores, a chemist at McGill University in Montreal, Canada, is tackling a bothersome issue in the pharmaceutical, cosmetics and food industries, which often use heavy-metal-ion catalysts. Ions of palladium, ruthenium and platinum are toxic, so products made with them cannot be sold until they have been through a series of meticulous and expensive cleansing steps. Moores is working on alternative catalysts based on iron, which is much safer.

In 2014, her research group prepared a series of hollow, magnetic iron oxide nanoparticles for making benzaldehyde¹¹: a molecule that smells like almonds and is widely used in flavourings. It is typically manufactured by reacting certain electron-hungry compounds with styrene: a sweet-smelling but hazardous liquid that is better known as a raw material for plastics. The process tends to generate a relatively small amount of benzaldehyde mixed with other molecules. But Moores' iron nanoparticles catalyse a more controllable reaction between styrene and oxygen, yielding almost pure benzaldehyde. And as an added advantage, iron is magnetic, so at the end of the reaction the iron nanoparticles can be extracted for reuse with a magnet.

Even-handedness

When making large, complex molecules such as steroids, antibiotics or hormones, a major challenge involves chirality, or the 'handedness' of a carbon atom. Such an atom carrying four different groups can have two configurations that are mirror images of each other, like human hands. A complex molecule may contain many such carbon atoms — and if even one of them has the wrong configuration, the compound can end up interacting badly with the human body. One notorious example is thalidomide, a drug developed in the 1950s for treating morning sickness in pregnant women. One chiral configuration seems to have been effective and safe for that purpose. But many chemists believe that its mirror image, which was present in the over-the-counter drug, is what caused babies to be born with severe limb deformations.

Molecules from biomass feedstocks contain a wide variety of chiral carbon atoms in a chain, and it is almost impossible to distinguish one from another. “A small-molecule catalyst wouldn't recognize it,” says Hartwig. Instead, chemists are turning to biological enzymes, which can be large enough to recognize the overall shape of the target molecule and home in on the bond where the reaction should occur. Enzymes also have the advantage of using water as a solvent and working at body temperatures, which makes them more environmentally friendly than processes that require toxic solvents and large amounts of heat.

Naturally occurring enzymes don't always catalyse the reactions that chemists want, however — which is why one frontier of catalysis research is to rework these proteins so that they do. Hartwig has been looking at the haem enzyme, which is similar to the compounds that carry oxygen in red blood cells, and has developed¹² an artificial enzyme that substitutes an iridium complex for the haem's iron centre. Although this runs contrary to the goal of replacing precious metals with Earth-abundant ones, says Hartwig, iridium can work with strong bonds such as those between carbon and hydrogen, which iron cannot. His team is using crystallographic data to study the enzyme's structures near the iridium site and is systematically modifying them so that they can precisely transform a carbon–hydrogen bond into a carbon–carbon bond with the desired chiral configuration — a formidable challenge. The chemists can prepare hundreds or even thousands of new enzymes in this way, limited only by the time it takes to test them and analyse their activity.

Still, enzymes are very specific to their target, and although they yield a product with a single chiral configuration, it is often the configuration that isn't wanted. “If you're interested in the other, you're in trouble,” says Stellios Arseniyadis, a synthetic chemist at Queen Mary University of London. To address that problem, Arseniyadis is collaborating with Michael Smietana of the University of Montpellier in France to make catalysts from DNA. Although most natural DNA spirals in only one direction, it is possible to make an artificial version that twists in the opposite direction. The two researchers and their teams make their catalysts by choosing a natural or non-natural helix of DNA and then attaching a metal ion inside it. The spiral grooves align the reactants so that they fuse with the desired chiral configuration. In 2015, Arseniyadis and Smietana reported a recyclable DNA–copper catalyst¹³ that created the correct chiral products as reactants flowed past. With endless combinations of base pairs and metal ions, “there's a plethora of parameters that you can fine-tune”, says Arseniyadis.

Chemists are continuing to push the boundaries of catalysis research. Li, for example, is experimenting with housing enzymes inside nanoparticles¹⁴ to help them last longer. Others are synthesizing completely artificial enzymes¹⁵ using techniques from synthetic biology. And earlier this year, an international team of researchers reported¹⁶ using an electric field to catalyse the formation of ring-shaped carbon compounds. These ideas are starting to constitute entire new research fields in which conventionally distinct disciplines overlap — for example, combining chemical synthesis and DNA. That, says Arseniyadis, leaves “a lot of room for serendipity”.

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US researchers build CNT FETS with current density of 900mA mm-1

University of Wisconsin-Madison materials engineers have created semiconducting single-walled carbon nano tubes (CNTs) that outperform state-of-the-art silicon and GaAs transistors.

The researchers reported their advance in Science Advances in a paper titled 'Quasi-ballistic carbon nano tube array transistors with current density exceeding Si and GaAs’.

Led by Michael Arnold and Padma Gopalan, the team developed carbon nano tube transistors with a current 1.9 times higher than silicon transistors. The on-state current density exceeds that of GaAs FETs.

This breakthrough in CNT array performance is said to be a critical advance toward the exploitation of CNTs in logic, high-speed communications, and other semiconductor electronics technologies.

A 100nm channel length CNT array FET developed by the team had a current density of 900 mA mm-1 which they say exceeds the 630 mA mm-1 demonstrated by other researchers for GaAs pseudomorphic high-electron mobility transistor (pHEMT) technology.

"This achievement has been a dream of nanotechnology for the last 20 years," says Arnold. "This breakthrough in carbon nano tube transistor performance is a critical advance toward exploiting carbon nano tubes in logic, high-speed communications, and other semiconductor electronics technologies."

The new transistors are particularly promising for wireless communications technologies that require a lot of current flowing across a relatively small area.

Carbon nano tube transistors should be able to perform five times faster or use five times less energy than silicon transistors, according to extrapolations from single nanotube measurements. The nano tube's ultra-small dimension makes it possible to rapidly change a current signal traveling across it, which could lead to substantial gains in the bandwidth of wireless communications devices.

But researchers have struggled to isolate purely carbon nano tubes, which are crucial, because metallic nano tubes impurities act like copper wires and disrupt their semiconducting properties - like a short in an electronic device.

The UW-Madison team used polymers to selectively sort out the semiconducting nano tubes, achieving a solution of ultra-high-purity semiconducting carbon nano tubes.

Placement and alignment of the nano tubes is also difficult to control. In 2014, the UW-Madison researchers overcame that challenge when they announced a technique, called "floating evaporative self-assembly," that gives them this control.

The nano tubes must make good electrical contacts with the metal electrodes of the transistor. Because the polymer the UW-Madison researchers use to isolate the semiconducting nano tubes also acts like an insulating layer between the nano tubes and the electrodes, the team "baked" the nano tubes arrays in a vacuum oven to remove the insulating layer. The result: excellent electrical contacts to the nano tubes.

The researchers also developed a treatment that removes residues from the nano tubes after they're processed in solution.

"In our research, we've shown that we can simultaneously overcome all of these challenges of working with nano tubes, and that has allowed us to create these groundbreaking carbon nano tubes transistors that surpass silicon and gallium arsenide transistors," says Arnold.

They are continuing to work on adapting their device to match the geometry used in silicon transistors, which get smaller with each new generation. Work is also underway to develop high-performance radio frequency amplifiers that may be able to boost a cellphone signal. While the researchers have already scaled their alignment and deposition process to 1 inch by 1 inch wafers, they're working on scaling the process up for commercial production.

The researchers have patented their technology through the Wisconsin Alumni Research Foundation.

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Where you live shapes your immune system more than your genes

Like fingerprints, immune systems vary from person to person. And although we all inherit a unique set of genes that help us respond to infections, recent studies have found that our history and environment--like where and with whom we live--are responsible for 60% to 80% of the differences between individual immune systems, while genetics account for the rest.

"Just like it took a while to crack the genetic code, we're finally starting to crack the immune code, and we're shifting away from the simplistic idea that there is only one type of immune system," says lead author Adrian Liston, head of the VIB-KU Leuven Translational Immunology Laboratory in Belgium. "Diversity isn't just programmed into our genes -- it emerges from how our genes respond to the environment."

Long-term infections are responsible for most of the differences between individual immune systems. For example, when a person has herpes or shingles, the virus has more opportunities to interact with the immune system. These interactions slowly change the cellular makeup of their immune system and make it more sensitive to that specific virus but also easier for other infections to slip past its defenses. People without these infections don't experience these cellular changes, and even with the occasional cold or fever, their immune systems stay relatively stable over time.

The exception is when a person is elderly. Researchers haven't determined exactly why age plays a major role in making our individual immune systems more unique, but they have shown that aging changes how our immune system responds to threats. As we get older, an organ called the thymus gradually stops producing T cells, which are made to help to fight off infection. Without new T cells, older people are more likely to get sick and less likely to respond to vaccines.

Beyond T cells, aging also seems to broadly change the way our immune systems react. "A lot of diseases that we associated with aging have an inflammatory component, which suggests there is likely immune involvement," says Michelle Linterman, a researcher at the Babraham Institute and co-author of the review. "Understanding how the immune system changes with age is going to be hugely important for treating age-related diseases in the future."

Differences can be overcome, however; studies of people living together have shown that air quality, food, stress levels, sleep patterns, and lifestyle choices had a strong combined effect on our immune responses. For example, couples who cohabitate have more similar immune systems compared to the general public.

Liston and his collaborators, Linterman and Edward Carr of the Babraham Institute, would next like to explore how changing our environment could purposefully shape our immune system and potentially affect our health. "In order to tinker with the immune code, we first need to really understand the influences that shape the immune system," says Liston. "That's why it's actually great that environment is more important than genetics, because we can play with environment."

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Benefits And Danger's of Honey

Honey has been valued as a natural sweetener long before sugar became widely available in the 16th century. Honey production flourished in ancient Greece and Sicily, for instance, while animals other than humans – bears, badgers, and more – have long raided honeybee hives, risking stings for the sweet reward.

Honey is truly a remarkable substance, made even more extraordinary by the process with which it is made. This blend of sugar, trace enzymes, minerals, vitamins, and amino acids is quite unlike any other sweetener on the planet.

And while honey is high in fructose, it has many health benefits when used in moderation (assuming you're healthy). Before I delve into those, here's a brief "lesson" on how honey is made...  

How Honey Is Made

It takes about 60,000 bees, collectively traveling up to 55,000 miles and visiting more than 2 million flowers, to gather enough nectar to make one pound of honey.

Once the nectar is gathered, the bee stores it in its extra stomach where it mixes with enzymes, and then passes it (via regurgitation) to another bee's mouth. This process is repeated until the nectar becomes partially digested and is then deposited into a honeycomb.

Once there, the honeybees fan the liquid nectar with their wings, helping the water to evaporate and create the thick substance you know as "honey." This honeycomb is then sealed with a liquid secretion from the bee's abdomen, which hardens into beeswax. AsLive Science reported:

"Away from air and water, honey can be stored indefinitely, providing bees with the perfect food source for cold winter months."

There are more than 300 kinds of honey in the US, each with a unique color and flavor that is dependent upon the nectar source. Lighter colored honeys, such as those made from orange blossoms, tend to be milder in flavor while darker-colored honeys, like those made from wildflowers, tend to have a more robust flavor.

5 Honey Facts You Might Not Know

Honey, particularly in its raw form, offers unique health benefits that you might not be aware of. Among them…

1.Honey Makes Excellent Cough "Medicine"

The World Health Organization (WHO) lists honey as a demulcent, which is a substance that relieves irritation in your mouth or throat by forming a protective film.

Research shows honey works as well as dextromethorphan, a common ingredient in over the counter cough medications, to soothe cough and related sleeping difficulties due to upper respiratory tract infections in children.

2.Honey Can Treat Wounds

Honey was a conventional therapy in fighting infection up until the early 20th century, at which time its use slowly vanished with the advent of penicillin. Now the use of honey in wound care is regaining popularity, as researchers are determining exactly how honey can help fight serious skin infections.

Honey has antibacterial, antifungal, and antioxidants activities that make it ideal for treating wounds. In the US, Derma Sciences uses Manuka honey for their Medihoney wound and burn dressings.

Manuka honey is made with pollen gathered from the flowers of the Manuka bush (a medicinal plant), and clinical trials have found this type of honey can effectively eradicate more than 250 clinical strains of bacteria, including resistant varieties such as:

• MRSA (methicillin-resistant Staphylococcus aureus)
• MSSA (methicillin-sensitive Staphylococcus aureus)
• VRE (vancomycin-resistant enterococci)

Compared to other types of honey, Manuka has an extra ingredient with antimicrobial qualities, called the Unique Manuka Factor (UMF). It is so called because no one has yet been able to discover the unique substance involved that gives it its extraordinary antibacterial activity.

Honey releases hydrogen peroxide through an enzymatic process, which explains its general antiseptic qualities, but active Manuka honey contains "something else" that makes it far superior to other types of honey when it comes to killing off bacteria.

That being said, research shows that any type of unprocessed honey helped wounds and ulcers heal. In one study, 58 of 59 wounds showed "remarkable improvement following topical application of honey."

3.Honey Improves Your Scalp

Honey diluted with a bit of warm water was shown to significantly improve seborrheic dermatitis, which is a scalp condition that causes dandruff and itching. After applying the solution every other day for four weeks, "all of the patients responded markedly." According to the researchers:

"Itching was relieved and scaling was disappeared within one week. Skin lesions were healed and disappeared completely within 2 weeks. In addition, patients showed subjective improvement in hair loss."

4.Help Boost Your Energy

A healthy, whole-food diet and proper sleep is the best recipe for boundless energy, but if you're looking for a quick energy boost, such as before or after a workout, honey can suffice. This is particularly true for athletes looking for a "time-released fuel" to provide energy over a longer duration.10

5.Reduce Allergy Symptoms

Locally produced honey, which will contain pollen spores picked up by the bees from local plants, introduces a small amount of allergen into your system. Theoretically, this can activate your immune system and over time can build up your natural immunity against it.

The typical recommendation is to take about a teaspoon-full of locally produced honey per day, starting a few months PRIOR to the pollen season, to allow your system to build up immunity. And the key here is local.

This approach only works because it has pollen of local plants you may be allergic to. Honey from other parts of the country simply won't work. While research on this has yielded conflicting results, one study found that, during birch pollen season, compared to the control group, the patients using birch pollen honey experienced:

• 60 percent reduction in symptoms
• Twice as many asymptomatic days
• 70 percent fewer days with severe symptoms
• 50 percent decrease in usage of antihistamines

Interestingly enough, there were few differences between the two honey groups (those who took regular honey, versus those who took honey that contained birch pollen.) However, the birch pollen honey group used less histamines than those who used regular honey. The authors concluded:

"Patients who pre-seasonally used birch pollen honey had significantly better control of their symptoms than did those on conventional medication only, and they had marginally better control compared to those on regular honey. The results should be regarded as preliminary, but they indicate that birch pollen honey could serve as a complementary therapy for birch pollen allergy."

Honey for Herpes

Good-quality honey offers several topical wound-care benefits that can explain some of its success as a remedy for herpes sores:

• It draws fluid away from your wound
• The high sugar content suppresses microorganism growth
• Worker bees secrete an enzyme (glucose oxidase) into the nectar, which then releases low levels of hydrogen peroxide when the honey makes contact with your wound

In one study, 16 adult subjects with a history of recurrent labial and genital herpes attacks used honey to treat one attack, and a commonly prescribed antiviral drug, Acyclovir cream, during another. (It's important to realize that neither the drug nor the honey will actually cure genital herpes. They only treat the symptoms.)

Interestingly, honey provided significantly better treatment results. For labial herpes, the mean healing time was 43 percent better, and for genital herpes, 59 percent better than acyclovir. Pain and crusting was also significantly reduced with the honey, compared to the drug. Two cases of labial herpes and one case of genital herpes remitted completely with the honey treatment, whereas none remitted while using acyclovir.

Dangers of Honey

The National Institutes of Health report you should never consume raw honey in order to prevent food poisoning, particularly if you are already immunocompromised. It’s especially dangerous to give raw honey to infants under the age of one. According to MayoClinic.com, giving raw honey to infants may cause infant botulism, a rare but serious gastrointestinal sickness caused by exposure to bacterial spores. Infant botulism can be life-threatening.

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Ear ossicles of modern humans and Neanderthals: Different shape, similar function

Scientists have scanned the skulls of Neanderthals and found the small middle ear ossicles, which are important for hearing, still preserved within the cavities of the ear. To their surprise, the Neanderthal ossicles are morphologically distinct from the ossicles of modern humans. Despite the differences in morphology, the function of the middle ear is largely the same in the two human species. The authors relate the morphological differences in the ossicles to different evolutionary trajectories in brain size increase and suggest that these findings might be indicative of consistent aspects of vocal communication in modern humans and Neanderthals. These findings are also of importance for shedding light on the emergence of human spoken language, which can only be inferred indirectly from the archaeological and fossil record.

The three bones of the middle ear (hammer, anvil, stapes) make up the ossicular chain. This bony chain, which is found in all mammals is dedicated to the transmission of sound waves from the tympanic membrane to the inner ear and helps in amplifying the energy of airborne sound in order to allow the sound wave to travel within the fluid-filled inner ear. Moreover, the ear ossicles are not only important for correct hearing but are also the smallest bones of our body. Thus, it does not surprise that the ossicles are among the most rarely found bones in the mammalian fossil record including the one of human ancestors. Given their important role in audition this lack of knowledge has ever been frustrating for researchers interested in studying hearing capacities of extinct species.

Tiny bones still present

This also applies to our closest extinct relatives -- the neanderthals whose communicative capacities including existence of human spoken language is a major scientific debate ever since the first discovery of neanderthal remains. A research team led by Alexander Stoessel from the Max Planck Institute for Evolutionary Anthropology in Leipzig used high-resolution computer tomography scans of neanderthal skulls and systematically checked for ossicles that potentially became trapped within the cavity of the middle ear. And indeed, the researchers found ear ossicles in 14 neanderthal individuals coming from sites in France, Germany, Croatia and Israel, resulting in the largest sample of ear ossicles of any fossil human species. "We were really astonished how often the ear ossicles are actually present in these fossil remains, particularly when the ear became filled with sediments" says lead researcher Alexander Stoessel.

After virtually reconstructing the bones, the team -- which also included scientist from the Friedrich-Schiller University in Jena and the University College in London -- compared them to ossicles of anatomically modern humans and also chimpanzees and gorillas which are our closest living relatives.

Since ossicles are not only small but also complex-shaped the researchers compared them by means of three-dimensional analysis that uses a much larger number of measuring points allowing for examination of the three-dimensional shape of a structure. "Despite the close relationship between anatomically modern humans and neanderthals to our surprise the ear ossicles are very differently shaped between the two human species" says Romain David who was involved in the study.

Based on the results of the morphological comparison the research team examined the potential reasons for these different morphologies. In order to see if these differences may affect hearing capacity of neanderthals and modern humans or reflects a tight relationship with the base of the skull they also analyzed the structures surrounding the ear ossicles. The outcome of this analysis was surprising, again since the functional parameters of the neanderthal and modern human middle ear are largely similar despite contrasting morphologies.

Similar communication skills in archaic humans

Instead, the team found the ear ossicles strongly related to the morphology of the surrounding cranial structures which also differ between the two human groups. The researchers attribute these differences to different evolutionary trajectories that neanderthals and modern humans pursued in order to increase their brain volume which also impacted the structures of the cranial base which the middle ear is a part of. "For us these results could be indicative for consistent aspects of vocal communication in anatomically modern humans and neanderthals that were already present in their common ancestor" says Jean-Jacques Hublin who is an author of this study and continues "these findings should be a basis for continuing research on the nature of the spoken language in archaic hominins."

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Automated screening for childhood communication disorders

For children with speech and language disorders, early-childhood intervention can make a great difference in their later academic and social success. But many such children -- one study estimates 60 percent -- go diagnosed until kindergarten or even later.

Researchers at the Computer Science and Artificial Intelligence Laboratory at MIT and Massachusetts General Hospital's Institute of Health Professions hope to change that, with a computer system that can automatically screen young children for speech and language disorders and, potentially, even provide specific diagnoses.

This week, at the Interspeech conference on speech processing, the researchers reported on an initial set of experiments with their system, which yielded promising results. "We're nowhere near finished with this work," says John Guttag, the Dugald C. Jackson Professor in Electrical Engineering and senior author on the new paper. "This is sort of a preliminary study. But I think it's a pretty convincing feasibility study."

The system analyzes audio recordings of children's performances on a standardized storytelling test, in which they are presented with a series of images and an accompanying narrative, and then asked to retell the story in their own words.

"The really exciting idea here is to be able to do screening in a fully automated way using very simplistic tools," Guttag says. "You could imagine the storytelling task being totally done with a tablet or a phone. I think this opens up the possibility of low-cost screening for large numbers of children, and I think that if we could do that, it would be a great boon to society."

Subtle signals

The researchers evaluated the system's performance using a standard measure called area under the curve, which describes the tradeoff between exhaustively identifying members of a population who have a particular disorder, and limiting false positives. (Modifying the system to limit false positives generally results in limiting true positives, too.) In the medical literature, a diagnostic test with an area under the curve of about 0.7 is generally considered accurate enough to be useful; on three distinct clinically useful tasks, the researchers' system ranged between 0.74 and 0.86.

To build the new system, Guttag and Jen Gong, a graduate student in electrical engineering and computer science and first author on the new paper, used machine learning, in which a computer searches large sets of training data for patterns that correspond to particular classifications -- in this case, diagnoses of speech and language disorders.

The training data had been amassed by Jordan Green and Tiffany Hogan, researchers at the MGH Institute of Health Professions, who were interested in developing more objective methods for assessing results of the storytelling test. "Better diagnostic tools are needed to help clinicians with their assessments," says Green, himself a speech-language pathologist. "Assessing children's speech is particularly challenging because of high levels of variation even among typically developing children. You get five clinicians in the room and you might get five different answers."

Unlike speech impediments that result from anatomical characteristics such as cleft palates, speech disorders and language disorders both have neurological bases. But, Green explains, they affect different neural pathways: Speech disorders affect the motor pathways, while language disorders affect the cognitive and linguistic pathways.

Telltale pauses

Green and Hogan had hypothesized that pauses in children's speech, as they struggled to either find a word or string together the motor controls required to produce it, were a source of useful diagnostic data. So that's what Gong and Guttag concentrated on. They identified a set of 13 acoustic features of children's speech that their machine-learning system could search, seeking patterns that correlated with particular diagnoses. These were things like the number of short and long pauses, the average length of the pauses, the variability of their length, and similar statistics on uninterrupted utterances.

The children whose performances on the storytelling task were recorded in the data set had been classified as typically developing, as suffering from a language impairment, or as suffering from a speech impairment. The machine-learning system was trained on three different tasks: identifying any impairment, whether speech or language; identifying language impairments; and identifying speech impairments.

One obstacle the researchers had to confront was that the age range of the typically developing children in the data set was narrower than that of the children with impairments: Because impairments are comparatively rare, the researchers had to venture outside their target age range to collect data.

Gong addressed this problem using a statistical technique called residual analysis. First, she identified correlations between subjects' age and gender and the acoustic features of their speech; then, for every feature, she corrected for those correlations before feeding the data to the machine-learning algorithm.

"The need for reliable measures for screening young children at high risk for speech and language disorders has been discussed by early educators for decades," says Thomas Campbell, a professor of behavioral and brain sciences at the University of Texas at Dallas and executive director of the university's Callier Center for Communication Disorders. "The researchers' automated approach to screening provides an exciting technological advancement that could prove to be a breakthrough in speech and language screening of thousands of young children across the United States."

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Baby's genes influence birth weight and later life disease

Genetic differences have been found that help to explain why some babies are born bigger or smaller than others. It also reveals how genetic differences provide an important link between an individual's early growth and their chances of developing conditions such as type 2 diabetes or heart disease in later life.

The large-scale study, published in Nature, could help to target new ways of preventing and treating these diseases.

The new study was jointly led by a team of researchers from six institutions including the universities of Exeter, Oxford, Bristol, Cambridge and Queensland, and the Erasmus Medical Centre in Rotterdam. The research involved more than 160 international researchers from 17 countries who are members of the Early Growth Genetics (EGG) Consortium. The work was supported by more than 120 research funders: the major sources of funding for UK researchers were the Wellcome Trust, the Royal Society, the Medical Research Council, the National Institute for Health Research and the European Union.

The research concluded that a substantial proportion (at least one-sixth) of the variation in birth weight is down to genetic differences between babies. This is seven to eight times more variation than can be explained by environmental factors already known to influence birthweight, such as the mother smoking during pregnancy or her body mass index (a measure of obesity) before pregnancy starts.

Dr Rachel Freathy, a Sir Henry Dale Fellow at the University of Exeter Medical School, who was joint lead author on the study, said: "This study has revealed how the small genetic differences between individuals can collectively have quite large effects on birth weight, and how those same genetic differences are often linked to poor health in later life. Weight at birth is influenced by many factors, including the baby's genes and those of its parents, as well as by the nutrition made available and the environment provided by the mother. We now have a much more detailed view of the ways in which these genetic and environmental elements work together to influence early growth and later disease."

It has been known for some time that babies whose birthweight is well below, or well above, average have a markedly increased risk of diabetes many decades later. Until now, many researchers have assumed that this link reflects the long-term impact of the nutritional environment in which the fetus develops: in other words, that events in early life can "set up" an individual's body in ways that make them more prone to disease in later life.

In this new study, the researchers uncovered a substantial overlap in the genetic regions linked to differences in birth weight and those that are connected to a higher risk of developing diabetes or heart disease. Most of this overlap involves the baby's genetic profile, but the team found that the mother's genes also played an important role in influencing her baby's birth weight, most likely through the ways in which they alter the baby's environment during pregnancy.

Professor Mark McCarthy at the University of Oxford, and co-lead author, said: "These findings provide vital clues to the some of the processes that act over decades of life to influence an individual's chances of developing diabetes and heart disease. These should highlight new approaches to treatment and prevention. Understanding the contributions of all of these processes will also tell us how much we should expect the many, wonderful improvements in antenatal care to reduce the burden of future diabetes and heart disease."

The researchers analysed genetic differences throughout the genomes of nearly 154,000 people from across the world. Around half of these came from the UK Biobank cohort. By matching the genetic profiles of these people to information on birth weight, the researchers could identify sixty regions of the genome that were clearly driving differences in birthweight. They then analysed data from previous studies on conditions including diabetes and heart disease, and found that many of the same genomic regions were implicated.

Dr Momoko Horikoshi, from the Wellcome Trust Centre for Human Genetics at the University of Oxford, co-lead author on the paper, continued, "Our results point to the key role played by genetic differences in connecting variation in early growth to future risk of disease. Our next steps will be to gather more pieces of the puzzle, including a better understanding of how the genetic profiles of mother and baby act together to modify the baby's weight and later disease risk."

Dr Rob Beaumont, at the University of Exeter Medical School, who worked on the study, said: "This study highlights the value of large-scale international research collaborations. It's really satisfying to bring together a wide range of experts to analyse largescale datasets to advance understanding in key areas of human health."

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