#Novel glycoengineering technology gives qualitative leap for biologics drug research Researchers from the University of Copenhagen have discovered a way of improving biotech drugs.
Better, cheaper and more effective drugs to combat cancer, arthritis and many other disorders. This is the result of a ground-breaking new technique developed by a group of researchers from the Faculty of health and Medical sciences at the University of Copenhagen.
The method can improve a large number of so-called glycoprotein-based pharmaceuticals used to treat a variety of diseases.
The technique has recently been described in one of the world's most distinguished scientific journals
Nature Biotechnology. If glycoprotein-based pharmaceuticals are to produce the desired effect, the protein must be provided with a special sugar structure for enhanced therapeutic effect and duration.
The production of glycoproteins is often based on hamster cells, which generate mixed and sometimes unusable sugar structures.
"Sugar structures are like a tree made from building blocks --and you could say that we have found a faster
"says researcher Zhang Yang from the Copenhagen Center for Glycomics, a centre of excellence at the University of Copenhagen.
Longer-lasting and improved therapeutic effect and not least, faster and cheaper production.""We have seen previously examples of optimised sugar structures making pharmaceuticals up to a hundred times more effective.
One example is antibodies for cancer patients, which--by the way--is a very expensive form of therapy,
"says Zhang Yang g
#Simulations lead to design of near-frictionless material While reviewing the simulation results of a promising new lubricant material,
'"said Subramanian Sankaranarayanan, Argonne computational nanoscientist, who led the simulation work at the Argonne Leadership Computing Facility (ALCF), a DOE Office of Science User Facility.
They were amazed by what the computer simulations revealed. When the lubricant materials--graphene and diamond-like carbon (DLC)--slid against each other,
the graphene began rolling up to form hollow cylindrical"scrolls"that helped to practically eliminate friction.
These so-called nanoscrolls represented a completely new mechanism for superlubricity a state in which friction essentially disappears."
Considering that nearly one-third of every fuel tank is spent overcoming friction in automobiles, a material that can achieve superlubricity would greatly benefit industry and consumers alike.
Arrayprior to the computational work, Argonne scientists Ali Erdemir, Anirudha Sumant, and Diana Berman were studying the hybrid material in laboratory experiments at Argonne's Tribology Laboratory and the Center for Nanoscale Materials,
a DOE Office of Science User Facility. The experimental setup consisted of small patches of graphene (a two-dimensional single-sheet form of pure carbon) sliding against a DLC-coated steel ball.
The graphene-DLC combination was registering a very low friction coefficient (a ratio that measures the force of friction between two surfaces),
but the friction levels were fluctuating up and down for no apparent reason. The experimentalists were puzzled also to find that humid environments were causing the friction coefficient to shoot up to levels that were nearly 100 times greater than measured in dry environments.
To shed light on these mysterious behaviors they turned to Sankaranarayanan and Deshmukh for computational help. Using Mira, the ALCF's 10-petaflops IBM Blue Gene/Q supercomputer,
the researchers replicated the experimental conditions with large-scale molecular dynamics simulations aimed at understanding the underlying mechanisms of superlubricity at an atomistic level.
This led to their discovery of the graphene nanoscrolls, which helped to fill in the blanks.
They tried incorporating nanodiamond particles into their simulations to see if the hard material could help stabilize the nanoscrolls
The graphene patches spontaneously rolled around the nanodiamonds, which held the scrolls in place and resulted in sustained superlubricity.
The simulation results fed into a new set of experiments with nanodiamonds that confirmed the same."
"This collaborative effort is a perfect example of how computation can help in the design and discovery of new materials."
"Arrayunfortunately, the addition of nanodiamonds did not address the material's aversion to water. The simulations showed that water suppresses the formation of scrolls by increasing the adhesion of graphene to the surface.
While this greatly limits the hybrid material's potential applications, its ability to maintain superlubricity in dry environments is a significant breakthrough in itself.
which could potentially be used for applications in dry environments, such as computer hard drives, wind turbine gears, and mechanical rotating seals for microelectromechanical and nanoelectromechanical systems.
Adding to the material's appeal is a relatively simple and cost-effective deposition method called drop casting.
it would leave the graphene and nanodiamonds on one side of a moving part, and diamond-like carbon on the other side.
However, the knowledge gained from their study is perhaps even more valuable, said Deshmukh. He expects the nanoscroll mechanism to spur future efforts to develop materials capable of superlubricity for a wide range of mechanical applications.
the graphene nanoscrolls could potentially work in humid environments as well.""Arraythe team's groundbreaking nanoscroll discovery would not have been possible without a supercomputer like Mira.
Replicating the experimental setup required simulating up to 1. 2 million atoms for dry environments and up to 10 million atoms for humid environments.
The researchers used the LAMMPS (Large-scale Atomic/Molecular Massively Parallel Simulator) code to carry out the computationally demanding reactive molecular dynamics simulations.
With the help of ALCF catalysts, a team of computational scientists who work directly with ALCF users,
The ALCF catalysts in collaboration with researchers from IBM, Lawrence Berkeley National Laboratory, and Sandia National Laboratories, optimized LAMMPS
and its implementation of Reaxff by adding Openmp threading, replacing MPI point-to-point communication with MPI collectives in key algorithms,
and leveraging MPI I/O. Altogether, these enhancements allowed the code to perform twice as fast as before."
"And with the recent announcement of Aurora, the ALCF's next-generation supercomputer, Sankaranarayanan is excited about where this line of research could go in the future."
"Given the advent of computing resources like Aurora and the wide gamut of the available two-dimensional materials and nanoparticle types,
we envision the creation of a lubricant genome at some point in the future, "he said.""Having a materials database like this would allow us to pick
and choose lubricant materials for specific operational conditions.""Contributors to the code optimization work include Nichols A. Romero, Wei Jiang,
Paul Coffman from IBM; Hasan Metin Aktulga from Lawrence Berkeley National Laboratory (now at Michigan State university;
#'Cancer Driver Gene'reduces metastasis in prostate cancer A gene that is responsible for cancer growth plays a totally unexpected role in prostate cancer.
Lukas Kenner from the Medical University of Vienna, the Veterinary University of Vienna, and the Ludwig Boltzmann Institiute for Cancer Research (LBI-CR) discovered a missing link for an essential role of Stat3
and IL-6 signalling in prostate cancer progression. Interleukin 6 (IL-6) is an important cytokine that controls the cell survival and tumor growth.
Hyperactive IL-6 may support cancer growth particularly as it controls STAT3, which was shown to have an oncogenic role in most tumours.
Many therapies are designed therefore to suppress IL-6 or STAT3. But the situation is different in prostate cancer.
Lukas Kenner's research group has shown that, contrary to expectations; active STAT3 suppresses cell growth in prostate tumours.
It activates the gene p14arf, which blocks cell division and thus inhibits tumour growth.""Using knockout mice,
which are preclinical model organisms, we can link IL-6/Stat3 signalling to ARF, an important gene for cell cycle control and decisions to grow or to arrest.
These findings have consequences for prostate cancer metastasis, "explained Jan Pencik, a Phd fellow in the lab, headed by Lukas Kenner.
For this reason, STAT3 and p14arf are suited ideally to act as biomarkers for the prognosis of this disease.
If these two factors are missing in tissue samples, the risk is increased massively that the tumour grows
as the predictive power of these proteins as biomarkers is twice as good as the previous gold standard.
As only about 10%of patients with prostate cancer die from the disease, this can help to prevent unnecessary therapeutic interventions with severe side effects such as incontinence and impotence.
A noninvasive nuclear medical test based on these findings might soon be able to replace the painful removal of tissue samples to be examined.
Receptor blockers can enhance prostate cancer The reversed role of interleukin 6 as an inhibitor of prostate cancer has an additional significance.
Blockade of interleukin 6 is used to treat other diseases such as rheumatoid arthritis. According to Kenner, this means that therapies that block the IL-6 pathway may enhance the growth of prostate cancer.
Thus, the drug that is used to treat inflammatory disease may exacerbate malignancies.""Applying IL-6/Stat3 blockers to clinical practice might be dangerous for patients with cancerous lesions,
further studies are mandatory to assess the possibility of increased cancer risk right now, "says coauthor of this study, Helmut Dolznig, also from the Medical University of Vienna.
The study was financed mainly by the LBI-CR and the FWF. These results have just been published in the distinguished scientific journal Nature Communications s
#Device keeps donor livers healthy outside the body until transplant The technique and device are part of a Phase 1 clinical trial at Toronto General Hospital (TGH),
University Health Network assessing the safety of the device, with subsequent phases examining its efficacy.
First developed at the University of Oxford, the device could potentially preserve a liver outside the body for up to 24 hours.
The device, called the Organox Metra, has been used in England, Edmonton, Spain, Germany and Belgium successfully in liver transplantation.
Clarence Mills, 43, received a deceased donor liver which has been placed on the device for almost 12 hours."
who was able to walk around the unit two days after his transplant. Mills says he was happy to volunteer to become the first patient to receive a liver that was improved by the new technology."
We will know how healthy that organ is before the transplant operation, "says Dr. Markus Selzner, a transplant surgeon in the Multi-Organ transplant Program at TGH,
co-investigator of the clinical trial and the transplant surgeon who performed the donor operation.
Dr. Selzner is also a clinician-scientist at the Toronto General Research Institute who modified the Steen preservation solution used in the device at TGH
and data gathered from the device at TGH. The new preservation solution decreases inflammation and protects the liver from injury.
The liver is the second organ in the body which can regenerate, after skin. Dr. Selzner estimates that many more donor livers could benefit from this technology,
The medical device encloses the liver in a sterile environment, circulating oxygenated blood and nutrients into the liver at body temperature, allowing it to improve
"says Dr. David Grant, Surgical Director of the Multi-Organ transplant Program, co-investigator of the clinical trial who also transplanted the donor liver,
which had been placed on the medical device, into the recipient.""This new technology can help us answer critical questions such as,
and predict organ function before the transplant occurs?'"'"Dr. Grant also praised the strong support and efforts of Trillium Gift of Life,
which coordinates organ and tissue donation across Ontario, in helping to ensure that the transplant team could begin their clinical trials with this new technique.
The technique of warm organ perfusion outside the body was pioneered by the Toronto Lung Transplant Program at TGH in 2008 by Drs.
Since 2012, there has been unprecedented an 28%increase in lung transplants at TGH as a result of this system.
500 patients waiting for a transplant in Ontario. More than 200 of these wait for a liver,
a national group that has been collecting annual surveillance data about children born to women with HIV in Canada since 1990."
chair of the Canadian Pediatric & Perinatal AIDS Research Group (CPARG) which runs the CPHSP.
"Women who receive combination antiretroviral therapy (cart) during pregnancy do not pass HIV on to their baby.
preventing the disease in infants as well as opportunities to improve care. They determined which populations are at greatest risk
and how public health officials are working with those groups. Since the 1990s about half of women with HIV delivering babies in Canada were born foreign.
Aboriginal women and women who use injection drugs were also at greater risk of having HIV in pregnancy
"The database has allowed us to assess the national burden of HIV infection through vertical transmission throughout the HIV/AIDS epidemic
"said Joel Singer, professor in the School of Population and Public health at UBC, who is presenting at IAS 2015."
"The researchers say this recent success stems largely from public health initiatives to ensure women in these high-risk populations are tested
and infants is to engage hard-to-reach populations in health care and allow them to access prenatal care,
#Long-sought discovery fills in missing details of cell'switchboard'A biomedical breakthrough, published in the journal Nature, reveals never-before-seen details of the human body's cellular switchboard that regulates sensory and hormonal responses.
The work is based on an X-ray laser experiment at the Department of energy's SLAC National Accelerator Laboratory.
and effective drugs with fewer side effects to treat conditions including high blood pressure, diabetes, depression and even some types of cancer.
The study has been hailed by researchers familiar with the work as one of the most important scientific results to date using SLAC's Linac Coherent light Source LCLS), a DOE Office of Science User Facility that is one of the brightest
The research, led by scientists at the Van Andel Research Institute in Michigan in collaboration with dozens of other scientists from around the globe,
a biochemistry and molecular biology professor at Thomas Jefferson University in Philadelphia who specializes in such research
"This work has tremendous therapeutic implications, "Benovic said.""The study is a critical first step and provides key insight into the structural interactions in these protein complexes."
a scientist at the Van Andel Research Institute in Michigan who led the experiment. The study notes that a wide range of drugs would likely be more effective
The microscopic arrestin-GPCR crystals which his team had produced painstakingly over years, proved too difficult to study at even the most advanced type of synchrotron, a more conventional X-ray source.
In the LCLS experiments, Xu's team used samples of a form of human rhodopsin--a GPCR found in the retina whose dysfunction can cause night blindness--fused to a type of mouse arrestin that is nearly identical to human arrestin.
Measuring just thousandths of a millimeter, the crystals--which had been formed in a toothpaste-like solution--were oozed into the X-ray pulses at LCLS,
"This important work is a prime example of how SLAC's unique combination of cutting-edge scientific capabilities,
and structural biology, are playing key roles in high-impact scientific discoveries.""Data analysis Helps Fill in Missing Piece Qingping Xu,
a scientist in the Joint Center for Structural genomics at SLAC's Stanford Synchrotron radiation Lightsource who helped to solve the 3-D structure,
said it took many hours of computer modeling and data analysis to help understand and refine its details."
"This structure is especially important because it fills in a missing piece about protein-binding pathways for GPCRS,
"he said. Even so, he noted that much work remains in determining the unique structures and docking mechanisms across the whole spectrum of GPCRS and associated signaling proteins.
#Self-assembling, biomimetic membranes may aid water filtration A synthetic membrane that self assembles and is produced easily may lead to better gas separation,
This biomimetic membrane is composed of lipids--fat molecules --and protein-appended molecules that form water channels that transfer water at the rate of natural membranes,
and transport proteins are amazing machines present in biological membranes, "said Manish Kumar, assistant professor of chemical engineering, Penn State."
"They have functions that are hard to replicate in synthetic systems.""The researchers developed a second-generation synthetic water channel that improves on earlier attempts to mimic aquaporins--natural water channel proteins--by being more stable and easier to manufacture.
and aligned than carbon nanotubes, another material under investigation for membrane separation. Kumar and co-authors report their development in a recent issue of the Proceedings of the National Academy of Science."
#Discovery about brain protein causes rethink on development of Alzheimer's disease Researchers at the University of Melbourne have discovered that a protein involved in the progression of Alzheimer's disease also has properties that could be helpful for human health.
The discovery helps researchers better understand the complicated brain chemistry behind the development of Alzheimer's disease, a condition that affects hundreds of thousands of Australians.
An international team of researchers, led by Dr Simon Drew at the University of Melbourne and Prof Wojciech Bal at the Polish Academy of Sciences, has revealed that a shorter form of a protein called beta amyloid,
may act as a sponge that safely binds a metal that can damage brain tissue when it's in excess.
Researchers have been interested intensely in the role of beta-amyloid in the development of Alzheimer's disease. This is because clumps of the protein are formed in brains of people with the illness.
In the late 1990s, high levels of copper were discovered within these clumps. Copper is essential to health,
Many scientists began to suspect that this copper might be contributing to the disease. They found that beta-amyloid can bind to copper indiscriminately
It also wraps around the metal in a way that prevents it from producing free radicals.""Given these properties and its relative abundance,
It's very different from the current view of how beta amyloid interacts with biological copper."
"So far, therapies aimed at lowering the production of beta amyloid have shown only a modest ability to slow cognitive decline
and the number of people affected by the Alzheimer's disease continues to grow. Dr Drew and the team from Poland are now working to develop a method for identifying the copper-bound form of the short beta amyloid in the body.
and how this may change in aging and disease.""If a beneficial role in copper balance can be established,
"As the amount of beta amyloid in the brain increases during Alzheimer's disease, the shorter form can also clump together
#Transparent, electrically conductive network of encapsulated silver nanowires The electrodes for connections on the"sunny side"of a solar cell need to be not just electrically conductive,
but transparent As well as a result, electrodes are made currently either by using thin strips of silver in the form of a coarse-meshed grid squeegeed onto a surface,
This is because silver is a precious metal and relatively expensive, and silver particles with nanoscale dimensions oxidise particularly rapidly;
meanwhile, indium is one of the rarest elements on earth crust and probably will only continue to be available for a few more years.
Mesh of silver nanowires Manuela Göbelt on the team of Prof. Silke Christiansen has developed now an elegant new solution using only a fraction of the silver
and entirely devoid of indium to produce a technologically intriguing electrode. The doctoral student initially made a suspension of silver nanowires in ethanol using wet-chemistry techniques.
She then transferred this suspension with a pipette onto a substrate, in this case a silicon solar cell.
As the solvent is evaporated the silver nanowires organise themselves into a loose mesh that remains transparent,
yet dense enough to form uninterrupted current paths. Encapsulation by AZO crystals Subsequently, Göbelt used an atomic layer deposition technique to gradually apply a coating of a highly doped wide bandgap semiconductor known as AZO.
AZO consists of zinc oxide that is doped with aluminium. It is much less expensive than ITO and just as transparent,
but not quite as electrically conductive. This process caused tiny AZO crystals to form on the silver nanowires,
enveloped them completely, and finally filled in the interstices. The silver nanowires measuring about 120 nanometres in diameter, were covered with a layer of about 100 nanometres of AZO
and encapsulated by this process. Quality map calculated Measurements of the electrical conductivity showed that the newly developed composite electrode is comparable to a conventional silver grid electrode.
However, its performance depends on how well the nanowires are interconnected, which is a function of the wire lengths and the concentration of silver nanowires in the suspension.
The scientists were able to specify the degree of networking in advance with computers. Using specially developed image analysis algorithms,
they could evaluate images taken with a scanning electron microscope and predict the electrical conductivity of the electrodes from them."
"We are investigating where a given continuous conductive path of nanowires is interrupted to see where the network is not yet optimum,
"explains Ralf Keding. Even with high-performance computers, it still initially took nearly five days to calculate a good"quality map"of the electrode.
The software is now being optimised to reduce the computation time.""The image analysis has given us valuable clues about where we need to concentrate our efforts to increase the performance of the electrode,
such as increased networking to improve areas of poor coverage by changing the wire lengths or the wire concentration in solution,"says Göbelt.
Practical aternative to conventional electrodes"We have developed a practical, cost-effective alternative to conventional screen-printed grid electrodes and to the common ITO type that is threatened
however by material bottlenecks,"says Christiansen, who heads the Institute of Nanoarchitectures for Energy conversion at HZB
and additionally directs a project team at the Max Planck Institute for the Science of Light (MPL).
Only a fraction of silver, nearly no shadow effects The new electrodes can actually be made using only 0. 3 grams of silver per square metre,
while conventional silver grid electrodes require closer to between 15 and 20 grams of silver.
In addition, the new electrode casts a considerably smaller shadow on the solar cell.""The network of silver nanowires is so fine that almost no light for solar energy conversion is lost in the cell due to the shadow,
"explains Göbelt. On the contrary, she hopes"it might even be possible for the silver nanowires to scatter light into the solar cell absorbers in a controlled fashion through
what are known as plasmonic effects. e
#Cooking up altered states Churning raw milk sufficiently creates butter. Squirting lemon juice coagulates it into curd.
These two phenomena are not as straightforward as they sound on the molecular level. When milk is churned,
the fat molecules in it come closer to form aggregates. Lemon juice increases milk's acidity
and creates similar molecular lumps. Yet butter and curd are not solids because in both cases,
the aggregated molecules still maintain consistent distances from each other, behaving as if they are part of a liquid.
There are similar liquids, both natural and human-made, where molecules pack together like a solid in certain localized regions of the bulk material.
Gels and shaving cream are crafted industrially examples. Recipes for creating such materials exist, but scientists do not always understand why they work.
Creating new types of functional materials from existing ones, therefore, depends on educated guesses and involves trial and error.
Joint research by the Okinawa Institute of Science and Technology Graduate University (OIST) and the Los alamos National Laboratory has discovered a way to predict the emerging structures
and bulk properties of new materials of this kind as they are crafted from variations of existing recipes.
"said Tamoghna Das, the paper's lead author and a postdoctoral scholar in the OIST Collective Interactions Unit.
#Heating and cooling with light leads to ultrafast DNA diagnostics New technology developed by bioengineers at the University of California, Berkeley,
and research applications of the polymerase chain reaction (PCR) test, with results coming in minutes instead of an hour or more.
PCR is used in the early diagnosis of hereditary and infectious diseases, and for analysis of ancient DNA samples of mummies and mammoths.
Using light-emitting diodes, or LEDS, the UC Berkeley researchers were able to heat electrons at the interface of thin films of gold and a DNA solution.
They clocked the speed of heating the solution at around 55 degrees Fahrenheit per second.
study senior author Luke Lee, a professor of bioengineering.""It is done usually in a lab
The PCR test requires repeated temperature changes--an average of 30 thermal cycles at three different temperatures--to amplify the genetic sequence,
or the interaction between light and free electrons on a metal's surface. When exposed to light
is a popular metal for this plasmonic photothermal heating because it is so efficient at absorbing light.
It has added the benefit of being inert to biological systems, so it can be used in biomedical applications.
For their experiments, the researchers used thin films of gold that were 120 nanometers thick,
or about the width of a rabies virus. The gold was deposited onto a plastic chip with microfluidic wells to hold the PCR mixture with the DNA sample.
The light source was an array of off-the-shelf LEDS positioned beneath the PCR wells. The peak wavelength of the blue LED light was tuned 450 nanometers
to get the most efficient light-to-heat conversion. The researchers were able to cycle from 131 degrees to 203 degrees Fahrenheit 30 times in less than five minutes.
who is also co-director of the Berkeley Sensor and Actuator Center.""It can be integrated into an ultrafast genomic diagnostic chip,
which we are developing for practical use in the field. Because this technology yields point-of-care results, we can use this in a wide range of settings, from rural Africa to a hospital ER
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