Synopsis: Biotech:


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By tweaking the genomes of these viruses, known as bacteriophages, researchers hope to customize them to target any type of pathogenic bacteria.

MIT biological engineers have devised a new mix-and-match system to genetically engineer viruses that target specific bacteria.

says Timothy Lu, an associate professor of electrical engineering and computer science and biological engineering.""These bacteriophages are designed in a way that's relatively modular.

Also, each family of bacteriophages can have a different genome organization and life cycle, making it difficult to engineer them

the researchers combed through databases of phage genomes looking for sequences that appear to code for the key tail fiber section, known as gp17.

they had to create a new system for performing the genetic engineering. Existing techniques for editing viral genomes are fairly laborious,

so the researchers came up with an efficient approach in which they insert the phage genome into a yeast cell,

where it exists as an"artificial chromosome"separate from the yeast cell's own genome.

During this process the researchers can easily swap genes in and out of the phage genome."

"Once we had that method, it allowed us very easily to identify the genes that code for the tails


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Other co-authors are UW computer science and neurobiology undergraduate student Darby Losey, UW bioengineering doctoral student Jeneva Cronin, UW bioengineering doctoral student Joseph Wu,


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#Scientists discover new system for human genome editing A team including the scientist who first harnessed the revolutionary CRISPR-Cas9 system for mammalian genome editing has identified now a different CRISPR system with the potential for even simpler and more precise

genome engineering. In a study published in Cell, Feng Zhang and his colleagues at the Broad Institute of MIT and Harvard and the Mcgovern Institute for Brain Research at MIT,

describe the unexpected biological features of this new system and demonstrate that it can be engineered to edit the genomes of human cells."

"This has dramatic potential to advance genetic engineering, "said Eric Lander, Director of the Broad Institute and one of the principal leaders of the human genome project."

"The paper not only reveals the function of a previously uncharacterized CRISPR system, but also shows that Cpf1 can be harnessed for human genome editing

and has remarkable and powerful features. The Cpf1 system represents a new generation of genome editing technology."

"CRISPR sequences were described first in 1987 and their natural biological function was described initially in 2010 and 2011.

The application of the CRISPR-Cas9 system for mammalian genome editing was reported first in 2013, by Zhang and separately by George Church at Harvard.

In the new study, Zhang and his collaborators searched through hundreds of CRISPR systems in different types of bacteria,

searching for enzymes with useful properties that could be engineered for use in human cells. Two promising candidates were the Cpf1 enzymes from bacterial species Acidaminococcus and Lachnospiraceae,

leaving'blunt ends'that often undergo mutations as they are rejoined. With the Cpf1 complex the cuts in the two strands are offset, leaving short overhangs on the exposed ends.

This could be an advantage in targeting some genomes, such as in the malaria parasite as well as in humans."

The Zhang lab also offers free online tools and resources for researchers through its website, http://www. genome-engineering. org.

with other enzymes that may be repurposed for further genome editing advances


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#Cabozantinib improves survival in patients with advanced kidney cancer: Results from the METEOR trial Patients with advanced kidney cancer live for nearly twice as long without their disease progressing


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Pioneered by Associate professor Leo Hwa Liang from the Department of Biomedical engineering at NUS'Faculty of engineering and Dr Jimmy Hon from the Department of Surgery at the NUS Yong Loo Lin School of medicine, this novel invention addresses a clinical gap in the current treatment of mitral valve regurgitation.

a current Biomedical engineering Masters student who is working on the design of the device under the supervision of Assoc Prof Leo,


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since completing his Phd in Molecular biology in 1997.""During my post-doc at the Max-Planck Institute in Germany,

Indeed, bioinformatic analysis led him to predict the existence of a mysterious protein: COCO, a"recombinational"human molecule that is normally expressed within photoreceptors during their development.


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led by Dr Esther Julián, of the Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, has discovered that one of these,

and with the group Bacterial Infections and Antimicrobial Therapies led by Dr Eduard Torrents, of the Institute for Bioengineering of Catalonia (IBEC) I


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Now, researchers at DTU Systems Biology have combined genetics with computer science and created a new diagnostic technology based on advanced self learning computer algorithms

are based on analyses of DNA mutations in cancer tissue samples from patients with metastasized cancer,

The pattern of mutations is analysed in a computer program which has been trained to find possible primary tumour localizations.

researchers have discovered several ways of using genome sequencing of tumours to predict whether an individual cancer patient will benefit from a specific type of medicine.

Associate professor Aron Eklund from DTU Systems Biology explains:""We are pleased very that we can now use the same sequencing data together with our new algorithms to provide a much faster diagnosis for cancer cases that are difficult to diagnose,

The method combines genetics and computer science, and can analyse a biopsy from a metastasis, and on this basis provide a number of possible scenarios for where the cancer may have developed


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or replaced by modern techniques that give the physician an indication of the elasticity of a biological tissue.


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'Complex array of mutations found in rare, aggressive leukemia Sezary syndrome (SS), an aggressive leukemia of mature T cells, is complicated more at a molecular level than ever suspected, according to investigators from the Perelman School of medicine at the University of Pennsylvania.

complementary gene sequencing approaches to look for mutations in tumor cells from SS patients: whole-genome sequencing in six subjects,

sequencing of all protein-coding regions (exomes) in 66 subjects, and comparing variation in the number of copies of all genes across the genome in 80 subjects."

"We did not expect the degree of genetic complexity that we found in our study,"Elenitoba-Johnson added.

They identified previously unknown recurrent loss-of-function mutations that target genes regulating epigenetic pathways--ones that act on how tightly

or loosely chromosomes are wound and thus accessible for genes to be expressed. One of these targets is called ARID1A,

and they found that loss-of-function mutations and/or deletions in ARID1A occurred in over 40 percent of the SS genome studied.

They also identified"gain-of-function"mutations in PLCG1, and JAK1, JAK3, STAT3 and STAT5B.

In preliminary drug-mutation matching studies they found that JAK1-mutated SS cells were sensitive to JAK inhibitors,

drugs that are approved currently for treatment of other hematologic cancers such as polycythemia vera and myelofibrosis."

"With knowledge like this, we can design clinical trials using JAK inhibitors for SS patients based on their JAK mutations,

"The Penn team, in collaboration with Alain Rook, MD, director of the Cutaneous T-cell Lymphoma Program and a professor of Dermatology, aims to develop a molecular taxonomy for mutations in SS patients.

From this, they will also be able to identify distinct subsets of the disease to stratify patients for precision therapy based on their unique mutations and the inhibitors available for those mutations s


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"In the short to medium term, the researchers hope to use their method to make printed, disposable biosensors, energy harvesters and RFID tags.


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#Bacterium capable of aquifer decontamination characterized, cultivated for first time in Europe UAB researchers have identified in the Besòs river estuary (Barcelona, Spain) a bacterium of the genus Dehalogenimonas,

This bacterial genus was described first not long ago--in 2009--and only two strains had previously been isolated, in chloroalkane-contaminated aquifers in Louisiana

though sequences of its genome have been identified in various locations, such as the Arctic ocean, the Baltic sea, Canada, China, Germany, Hungary, Spain, Taiwan and the USA.

and subsequent application in contaminated aquifers, using the strategy of bioaugmentation, which involves adding bacteria with specific catabolic capacities

and that bioaugmentation is a low-cost, efficient technique, compatible with other remediation techniques, these bacteria could even be applied eventually at source,

& Technology, was conducted at the Universitat Autònoma de Barcelona (Department of Chemical engineering and Department of Genetics and Microbiology) in collaboration with the University of Barcelona (Research Group in Applied Mineralogy and Fluid Geochemistry) and the Helmholtz Centre


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Nanotechnology, Biology and Medicine. While current HIV treatments involve pills that are taken daily, the new regimens'long-lasting effects suggest that HIV treatment could be administered perhaps once or twice per year.


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borrowing tools from the developing field of optogenetics, which so far has been used mainly in brain science.

'Optogenetics uses genetic modification to alter cells so that they can be activated by light. Until now, it has mainly been used to activate individual cells

'A protein called channelrhodopsin was delivered to heart cells using gene therapy techniques so that they could be controlled by light.

However, as gene therapy moves into the clinic and with miniaturization of optical devices, use of this all-optical technology may become possible.


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Rice bioengineer David Zhang and his colleagues have developed a unique way to adjust their nucleic acid probe reagents on the fly

especially mutations, has become critically important for the detection of diseases and design of therapies to treat them.

But finding a specific biomarker in a massive amount of genetic code is hard. Zhang and his team at Rice's Bioscience Research Collaborative have become specialists in finding such needles in haystacks.

In previous work, the lab designed probes that find single-nucleotide mutations in DNA while using"competing"probes to bind to healthy sequences

and effectively get them out of the way. This time the lab is developing synthetic DNA"protectors"that mimic the target sequence

"In one of many successful tests, the lab designed molecules to detect mutation sequences in historic biopsy samples preserved in wax from cancer patients.

faster and cheaper answers for researchers and clinicians who are looking at hundreds or thousands of different mutations,


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Dassarma, Phd, a professor of microbiology and immunology at the school,"GVNPS offer a designer platform for vaccines


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#Genome-edited plants, without DNA The public and scientists are at odds over the safety of genetically modified (GM) food.

Scientists at the IBS Center for Genome Engineering in South korea have created a way to genetically modify plants using CRISPR-Cas9 without the addition of DNA.

the resulting genome-edited plants could likely be exempt from current GMO regulations and given a warmer reception by the public.

so groundbreaking is that these genetic modifications look just like genetic variations resulting from the selective breeding that farmers have been doing for millennia.

IBS Director of the Center for Genome Engineering Jin-Soo Kim explains that"the targeted sites contained germline-transmissible small insertions

or deletions that are indistinguishable from naturally occurring genetic variation.""CRISPR is an acronym for Clustered Regularly Interspaced Short Palindromic Repeat,

CRISPR is used now widely for genome editing. What's crucial in genetic engineering is for the gene editing tool to be accurate and precise,

which is where CRISPR-Cas9 excels. CRISPR-Cas9 uses a single GUIDE RNA (sgrna) to identify

and no longer uses DNA, being unshackled from GMO regulations. To do this, purified Cas9 protein was mixed with sgrnas targeting specific genes from three plant species to form preassembled ribonucleoproteins (RNPS.

lettuce and rice to achieve targeted mutagenesis in protoplasts. To test the efficacy of this process,

and foundcas9 RNP-induced mutations 24 hours after transfection. These newly cloned lettuce cells showed no mosaicism

Finally, the team demonstrated that RGEN-induced mutations were maintained after regeneration. Using a Cas9 RNP

They grew full plants from the seeds of these genome edited and regenerated plants, which had the mutation from the previous generation.

They were able to definitively show that Cas9 RNPS can be used to genetically modify plants,

which Jin-Soo Kim points out,"paves the way for the widespread use of RNA-guided genome editing in plant biotechnology and agriculture."

"The IBS team's technique of genome editing without inserting DNA could be revolutionary for the future of the seed industry.

Currently European union GMO regulations don't allow for food with added DNA. Since the Cas9 RNP technique does not use DNA,

faster and more accurate to apply to plants than previous breeding techniques (like radiation-induced mutations).


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or sample preparation,"said Tomasz Tkaczyk, associate professor, Department of Bioengineering, Rice university, Houston, Texas."Many systems which work for point-of-care applications have quite expensive cartridges.

"Tkaczyk's co-authors on this research included Rebecca Richards-Kortum, Fellow of The Optical Society and a professor in Rice's Department of Bioengineering.


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and works by analyzing an interference pattern created when a beam of light that travels through a biological sample,


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This technological breakthrough hails opportunities for the development of smaller and cheaper sensors for various fields such as consumer electronics, information and communication technology, biotechnology and automotive.


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A device that detects in saliva a biological indicator of a possible risk of TYPE II DIABETES is the development of a technological and scientific team of the Tec de Monterrey (Mexican University) in collaboration with the University of Houston.

where the specific marker shows in a few seconds,"explains project coordinator Dr. Marco Antonio Rite Palomares, director of the Biotechnology Center of the Tec de Monterrey FEMSA.

The director of FEMSA Biotechnology Center mentions that he considered using the camera phone to detect the marker in saliva,

and is applied now to biology.""While the idea is to make the patient's life easier,


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"Ferritin, which is as close as biology has given us to a naturally magnetic protein nanoparticle,

"says Alan Jasanoff, an MIT professor of biological engineering and the paper's senior author.""We used the tools of protein engineering to try to boost the magnetic characteristics of this protein."


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Taking advantage of the layered structure of many biological specimens, Sebastian Streichan and Idse Heemskerk created the Image Surface Analysis Environment (Imsane),

"Such data allows us to answer basic questions about developmental biology and the role of physics in shaping the developing body,"Heemskerk added.

"Often in biology, the action is curved on a surface of interest. Although the recording of the cube containing this surface is 2 TB,

"The program is especially useful for biologists who otherwise would have to acquire the skillset and hardware to handle large data


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"For a long time, there has indeed been a hypothesis that VRAC plays a decisive role in apoptosis

Arraythe recent study also confirmed the hypothesis concerning apoptosis. If the protein LRRC8A, vital for VRAC, was put out of action,

"The suppression of apoptosis is probably due to the fact that, in the absence of volume-regulating VRAC,

the cell shrinkage observed in programmed cell death no longer functions. This has nothing to do with the mechanism of medication uptake."

Researchers led by Sven Rottenberg of the Cancer Research Centre in Amsterdam also identified LRRC8D as a relevant gene in a genome-wide screen for cellular cytostatic resistance.


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"In the near future, the group plans to apply their method to a wide range of biological materials,


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they form a biological film over the titanium to protect themselves from antibiotics. Once the implant is colonized by germs,


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A team of microbiologists based at the University of California, Berkeley, recently figured out one such new way of detecting life.

The basic structure of the current tree goes back 40 years to the microbiologist Carl Woese, who divided life into three domains:

director of the U s. Department of energy Joint Genome Institute. hen we got microscopes, and got microbes.

and sent it to the Joint Genome Institute for sequencing. What they got back was a mess.

when performing metagenomic analysisequencing scrambled genetic material from many organisms at once. The Berkeley team began the reassembly process with algorithms that assembled bits of the sequenced genetic code into slightly longer strings called contigs. ou no longer have tiny pieces of DNA,

you have bigger pieces, Brown said. hen you figure out which of these larger pieces are part of a single genome.

This part of the process, in which contigs are combined to reconstruct the genome sequence is called genome binning.

To execute it, the researchers relied on another set of algorithms, customized for the task by Itai Sharon,

a co-author of the study. They also assembled some of the genomes manually, making decisions about

what goes where based on the fact that some characteristics are consistent for a given genome.

For example, the percentage of Gs and Cs will be similar on any part of an organism DNA.

the researchers had eight full bacterial genomes and 789 draft genomes that were roughly 90 percent complete.

Some of the organisms had been glimpsed before; many others were completely new. The reason no one had found these organisms before is that the traditional method used to search for small forms of life doesn work for everything.

because the genetic code it contains is unique for every organism. When confronted with a DNA stew,

By reconstructing complete or nearly complete genomes, Brown and his collaborators were able to locate 16s rrna genes

All the organisms they found have very short genomes about one million base pairs (compare that to E coli,

300 to 1, 500 phyla that microbiologists estimate wel have once a complete accounting is finished.

and genome binning make Brown and Banfield optimistic, though, that it won be long before wee mapped them all. think that much of the tree of life will come into view in the next few years,


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Other biological molecules do not appear to interfere with the probe. Wei says the ethod could

Biosensors experts are enthusiastic about the sensor. Ben Zhong Tang from the Hong kong University of Science and Technology particularly likes the design

and envisages that his smart strategy will generate a large array of light up biosensors with outstanding performance.

And Kenneth Kam-Wing Lo from the City university of Hong kong says his interesting work will inspire the development of molecular probes and assays for biomolecules with high selectivity and sensitivity.


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A similar"synthetic biology"technique is used already to make artemisenin, a key malaria-drug ingredient that was derived previously from trees (see Reuters story of August 12, 2014, http://reut. rs/1j2ovkj).

"said Stanford university bioengineering professor Christina Smolke, who led the research published in the journal Science.


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says biological engineer Theodore Berger at the University of Southern California (USC) in Los angeles. That is because repeated seizures can destroy the brain tissue needed for long-term-memory formation.

says neuro biologist Howard Eichenbaum at Boston University in Massachusetts. But he cautions that mimicking it could be difficult


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and users simultaneously benefit from learning how to conduct microbiology experiments. Post/Biotics are using the power of an unlimited amount of citizen scientists to increase the research potential of antibiotic discovery.


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UC San francisco scientists identified a biological escape hatch that explains the resistance, and developed a strategy in mice for shutting it down.

Between 10 and 35 percent of non-small cell lung cancer (NSCLC) patients carry mutations in a gene that codes for a cell-surface protein called the epidermal growth factor receptor, or EGFR.

But the EGFR mutations seen in NSCLC cause the receptor to be stuck in an nposition, leading to rampant cell proliferation.

Understanding the biological basis of acquired resistance has proved difficult, partly because patients with late-stage lung cancer rarely undergo surgery,

and Evangelos Pazarentzos, Phd, a postdoctoral fellow, the research group analyzed cells from this tumor using next-generation genome sequencing in an effort to understand how the cells sidestepped erlotinib treatment.

They found that the tumor cells retained the EGFR mutation targeted by erlotinib and had acquired not additional cancer-driving mutations,

or any other mutations known to confer drug resistance. These results suggested that the cells were still potentially susceptible to erlotinib,

but had enlisted some additional mechanism to survive treatment. That mechanism was revealed when cells from the tumor were implanted in mice that were treated then with erlotinib.

and they discovered that this increase is mediated by a previously unknown biochemical complex formed within the tumor cells.


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and enhancersieces of the genome that control gene activityy chemically manipulating proteins that package DNA.

This web of biomolecules that supports and controls gene activity is known as the epigenome. The researchers say having the ability to steer the epigenome will help them explore the roles that particular promoters

or the risk for genetic disease and it could provide a new avenue for gene therapies and guiding stem cell differentiation. he epigenome is associated everything with the genome other than the actual genetic sequence,

and is just as important as our DNA in determining cell function in healthy and diseased conditions,

assistant professor of biomedical engineering at Duke. hat becomes immediately obvious when you consider that we have over 200 cell types,

explained Gersbach. ut there also many other pieces of the genome called enhancers that aren next to any genes at all,

Timothy Reddy, assistant professor of biostatistics and bioinformatics at Duke, has spent the better part of a decade mapping millions of these enhancers across the human genome.

Reddy thought perhaps he could chemically alter the histones at the enhancers to turn them on. here are already drugs that will affect enhancers across the whole genome,

and modify very specific epigenetic marks in very specific places to find out what individual enhancers are doing.

Reddy found that specificity by teaming up with Gersbach, his neighbor within Duke Center for Genomic and Computational biology,

and paste DNA sequences in the human genome. For this epigenome editing application, Gersbach silenced the DNA-cutting mechanism of CRISPR

Gersbach and Reddy put their artificial epigenetic agent to the test by targeting a few well-studied gene promoters and enhancers.

But the real excitement from their results is an emerging ability to probe millions of potential enhancers in a way never before possible. ome genetic diseases are straightforwardf you have a mutation within a particular gene,

Many different variations in the genome sequence can affect your risk of disease and this genetic variation can occur in these enhancers that Tim has identified,

where they can change the levels of gene expression. With this technology, we can explore what exactly it is that theye doing

and how it relates to disease or response to drug therapies. Gersbach added, ot only can you start to answer those questions,

but you might be able to use this technique for gene therapy to activate genes that have been silenced abnormally


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Assistant professor Ajai Vyas from NTU School of Biological sciences said he findings from the research clearly show the potential of enhancing the growth of brain cells using deep brain stimulation. round 60 per cent of patients do not respond to regular antidepressant treatments


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#Biologists identify brain tumor weakness Biologists at MIT and the Whitehead Institute have discovered a vulnerability of brain cancer cells that could be exploited to develop more-effective drugs against brain tumors.

a professor of medicine and cellular biology at Northwestern University who was not part of the research team.


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which was isolated originally by Johannes Scheid in the Nussenzweig laboratory, targets the CD4 binding site of the HIV envelope,

and the CD4 receptor is the primary site of attachment of HIV to host cells,


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and new biological ways to identify and stratify the ASD population into clinical sub-types


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added co-author Pier Paolo Pandolfi, the HMS George C. Reisman Professor of Medicine and director of the Cancer Genetics Program at Beth Israel Deaconess,


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#Computer-Designed Rocker Protein Worlds First To Biomimic Ion Transport For the first time, scientists recreated the biological function of substrate transportation across the cell membranes by computationally designing a transporter protein.

Protein engineering lags far behind the genetic engineering of modifying DNA that has been around since the 1970s.

Grabe views it as a first step in advancing the new discipline of protein engineering to the level of genetic engineering,


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Jacob Cheadle and Deadric T. Williams and was published online in the American Journal of Human biology s


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#Electrolyte Genome Could Be Battery Game-Changer A new breakthrough batteryne that has significantly higher energy,

But Lawrence Berkeley National Laboratory (Berkeley Lab) scientist Kristin Persson says she can take some of the guesswork out of the discovery process with her Electrolyte Genome.

and the Electrolyte Genome would return a short list of promising candidate molecules, dramatically speeding up the discovery timeline. lectrolytes are a stumbling block for many battery technologies,

Persson Electrolyte Genome, launched more than two years ago, uses high-throughput computer screening to calculate the properties

the Electrolyte Genome offers two other significant advantages to battery scientists. The first is that it could generate novel ideas. hile there are some amazing organic chemists out there,

The second advantage of the Electrolyte Genome is that it can add to scientistsfundamental understanding of chemical interactions. t adds explanations to why certain things work

How it works funnel method The Electrolyte Genome uses the infrastructure of the Materials Project, a database of calculated properties of thousands of known materials,

Early success stories The Electrolyte Genome first major scientific findinghat magnesium electrolytes are very prone to forming ion pairs,


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a Curators Professor of Animal Science and a professor of biochemistry, and his colleagues, says these new stem cells can help advance research on preeclampsia and a number of other areas of the human reproductive process. hese new cells,

They also added two other drugs that temporarily inhibited key biochemical pathways associated with the pluripotent state of the stem cells.

meaning that all the cells in the culture are quite similar to each other in the way they express their genetic information. reviously,


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