Reviewed by James Ives, M.Psych. (Editor)Jan 28 2019Researchers at LSTM and Imperial College London have designed drugs which could help combat any potential new flu pandemic, by targeting the receptors of the cells by which the virus gains entry to the human body.In a paper published today(link is external) in the Journal of Immunology the team, led by LSTM’s Professor Richard Pleass, show that by engineering a part of an antibody they can target the viral proteins that allow flu to mutate and become so deadly to humans.Last year marked the centenary of the 1918 influenza pandemic that claimed nearly 100 million lives worldwide, thus becoming the deadliest disease outbreak in recorded history. Global annual influenza outbreaks account for 300,000-650,000 respiratory deaths, mostly in children and the elderly.Related StoriesResearchers map virulence factor of influenza A virus in real-timeNaturally occurring human antibody reveals hidden weakness in influenza virusDrugs designed with advanced computing technologies could help tackle hospital superbugsProfessor Pleass explained: “Influenza vaccines have limited public health impact during pandemics, and current influenza vaccines are less efficacious than vaccines for many other infectious diseases. This is because influenza viruses that circulate in human and animal populations mutate two key viral surface proteins, haemagglutinin (HA) and neuraminidase (NA), thus allowing them to escape from protective antibodies produced through natural infection or vaccination”Both HA and NA target a sugar called sialic acid, that is found in abundance on the receptors of cells lining the mammalian respiratory tract, which the virus uses to gain entry into the body. The sialic acid-binding contacts on HA and NA do not mutate readily, otherwise the virus would not be able to infect human cells.The team has engineered antibody Fc fragments with enhanced sialic acid that target these conserved parts of both HA and NA, binding influenza viruses and thus blocking their interactions with human cells.By targeting sialic acid, these engineered biologicals may also be useful in the control of other pathogens, such as group B streptococci, Streptococcus pneumoniae, Mycoplasma genitalium, and Newcastle Disease Virus.”Better anti-influenza therapeutics are urgently needed.” Continued Professor Pleass: “The transfer of antibodies from people recovering from influenza during the 1918 and 2009 pandemics reduced mortality from influenza by 50% and 26% respectively. However, to be useful, these antibody medicines (also called FLU-IVIG) need to be manufactured in advance of future epidemics, which is obviously problematic as there may be modest or little neutralising activity against newly emerging strains. Therefore, combinations of existing medicines, including FLU-IVIG, with sialic acid blockers could increase their efficacy while future-proofing against the next pandemic.”Professor Sara Marshall, Head of Clinical and Physiological Sciences at the Wellcome Trust, who provided funding for this work, said: “This is a fascinating project, and one which could have really far-reaching impact not only for influenza but as a platform technology to develop new medicines for many other diseases that are currently treated by antibodies.” Source:https://www.lstmed.ac.uk/news-events/news/lstm-and-imperial-college-researchers-design-new-anti-influenza-drugs
What is CRISPR/Cas9? CPISPR applications CRISPR: Ethical and Safety Concerns CRISPR: The End for Zinc Fingers? How Does CRISPR Compare to Other Gene-Editing Techniques? How CRISPR is Revolutionizing Biomedical Research CRISPR-Cas14: Discovery, Function, Advantages By Dr. Liji Thomas, MDJun 4 2019In 2018, Chinese scientist He Jiankui defied the law and scientific consensus by boldly editing the CCR5 gene in a human embryo, expecting to confer lifelong HIV resistance. The pregnancy eventually ended in the birth of two baby girls. Now the experiment appears to have gone seriously wrong, perhaps shortening their lives.Using the powerful gene-editing tool called CRISPR/Cas9 on a human embryo to cut and insert new DNA, Professor He changed the original CCR5 gene in the embryo to a mutated version called Delta32. A similar mutation is naturally present in about one in ten individuals of European origin, who are resistant to HIV infection. New research at the University of California, Berkeley, suggests that, to the contrary, when both copies of this gene are disabled, the lifespan is actually likely to be shortened by 1.9 years on average.The researchers who brought out this study, published in the journal Nature Medicine, analyzed data on DNA and causes of death in over 400 000 British volunteers from the UK Biobank. What they found was shocking – without at least one functioning CCR5 gene, there was a 20% drop in the lifespan.In other words, such individuals were 20% less likely to live up to the age of 76 years.This is probably because they are more prone to other more common illnesses like West Nile virus and influenza.The scientists also noted that fewer than expected numbers of people with this mutation were registered in the data bank, possibly because they were more likely to have died earlier than the general population.Geneticist David Curtis of University College, London, commented: “There are many other examples in medicine where an intervention intended to treat one condition inadvertently causes major unexpected problems elsewhere.”The experiment provoked national scientific and governmental outrage, with China closing down He’s gene-editing activity in November 2018, citing serious violation of legislation and of medical ethics. The foremost concern in the minds of most scientists was the lack of data on the overall importance and role of the CCR5 gene to human life.An earlier study published this year in the journal Cell indicated a possible link between this gene and brain function as well as with immunity. In other words, many genes have multiple functions apart from the ones we already know about, and tinkering with just one gene may affect the life system in many unexpected and even lethal ways. As Rasmus Nielsen, who led the new study, points out, “We know it has many different effects. The question is: Is it overall beneficial or detrimental to have this mutation? That was not known.”In the light of current findings, he further notes: “It is probably not a mutation that most people would want to have.”CRISPR has stolen the limelight in the gene editing field with its simplicity, power, precision and cheapness. However, this has also led to the unwarranted expansion of its use without the required stringent guidelines, as in Professor He’s experiment.A few geneticists are in favor of human gene-editing, arguing that all new technologies have unknown cons when first introduced. They feel that attention should be focused on the risk-benefit ratio rather than on gene-editing technology, per se.This kind of defense worries other scientists who fear that using the technology too early in its lifecycle will produce harm rather than good. Many studies have already produced initial evidence that CRISPR is not as precise in its effects as previously thought, and may cause collateral damage to other genes.In addition, its use may reduce the immune defenses against cancerous changes in cells.Gene editing, or genetic modification, introduces changes which are then passed down from generation to generation, to potentially influence the entire pool of human genes. We could actually be creating uncontrollable and incurable diseases far down into the future, because we don’t yet know all the effects of these gene changes.This is one primary reason why scientists have generally stayed away from the use of this technology in embryonic humans so far.The take-home? It’s not yet time to edit genes in people, since we simply don’t know enough about all that each gene does. “Introduction of new or derived mutations in humans using Crispr technology… comes with considerable risk even if the mutations provide a perceived advantage,” the study authors sum up. Further Reading 3D Rendering Crispr DNA Editing. Image Credit: Nathan Devery / Shutterstock The CCR5 gene expresses itself as a cell surface protein on certain types of immune cells, providing the portal for HIV entry into the cell. Blocking this gene’s function essentially prevents HIV infection, theoretically prolonging life. Sources: The hidden cost of genetic resistance to HIV-1, JO, Nature Medicine, AB, 1546-170X, UR, https://doi.org/10.1038/s41591-019-0481-8, DO – 10.1038/s41591-019-0481-8, https://www.nature.com/articles/s41591-019-0481-8 CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury, Mary T. Joy, Einor Ben Assayag, Dalia Shabashov-Stone, Alcino J. Silva, Esther Shohami, S. Thomas Carmichael Cell, VOLUME 176, ISSUE 5, P1143-1157.E13, FEBRUARY 21, 2019, https://doi.org/10.1016/j.cell.2019.01.044, https://www.cell.com/cell/fulltext/S0092-8674(19)30107-2#secsectitle0020
Citibike station in midtown Manhattan. Credit: Jim Henderson, CC BY Seattle turned to dockless companies to fill the gap after a publicly funded dock bike-share system there failed in 2016. The city could soon have one of the largest bike-share systems in the country. Cities around Boston that are outside of the service area of Hubway, the area’s public bike-share system, just reached a deal to provide dockless bike-share service, expanding access to hundreds of thousands of people. And in San Francisco, Uber recently purchased Jump Bikes, a dockless electric bike-share startup, and soon will allow users to reserve electric bikes with their Uber app. If recent examples are any indication, bike sharing in the United States will be a mix of complementary dock-based and dockless systems, run by both public entities and private companies. The humble bicycle, aided by smartphone technology, is resurging as an urban transportation option. Officials in Dallas warn dockless bike-share companies to keep bikes from blocking sidewalks, ramps and trails. Dockless systems are also helping to address equity issues posed by public dock-based systems, which often are located in more affluent and predominantly white urban neighborhoods. Because dockless systems don’t require stations, they can be rapidly deployed in zones that dock-based systems may be slow to reach. Students at Beijing University developed this approach in 2014 to improve campus mobility. Dockless bike-share companies have flooded Chinese cities with bikes in the past two years, leading to massive piles of discarded bicycles in public spaces. The modern concept of bike sharing – offering bikes for short-term public rental from multiple stations in cities – was launched in Copenhagen in 1995, but U.S. cities only started piloting their own systems in the past decade. Washington D.C. led the way, launching SmartBike DC in 2008 and an expanded network called Capital Bikeshare in 2010. This program now boasts over 480 stations and a daily ridership of 5,700. Within a few years, bike-share systems launched in Boston, New York, Chicago, San Francisco, Seattle and dozens of other cities. In 2016 there were 55 systems across the country with a total of over 40,000 bikes. And momentum continues to grow. In 2017 Citi Bike in New York City added 2,000 bikes, increasing its fleet to a total of 12,000. San Francisco is expanding its system from just 700 bikes to 7,000, thanks to a sponsorship deal with Ford. Going docklessThe newest twist in this rapid expansion is dockless bike sharing, which lets users park bikes anywhere within defined districts and lock and unlock their bikes with smartphone apps. Users don’t have to locate docking stations or worry about whether space will be available at their destination. These systems also are cheaper to set up, so providers can charge lower user fees. Some dockless bike-share companies offer rides for as little as US$1 for the first half hour. Provided by The Conversation Dockless bike-share hits US capital, following craze in China (Update) Dockless cycle share bike in Seattle. Credit: Joe Mabel, CC BY Explore further Citation: Bike-share companies are transforming US cities – and they’re just getting started (2018, April 19) retrieved 18 July 2019 from https://phys.org/news/2018-04-bike-share-companies-cities-theyre.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only. Residents of major U.S. cities are becoming used to seeing docks for bike sharing programs nestled into parking spaces or next to subway station entrances. Adorned with stylish branding and corporate sponsors’ logos, these facilities are transforming transportation in cities across the country. This article was originally published on The Conversation. Read the original article.
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only. When solving multicriteria optimization problems, the complexity of computations substantially increases when it is necessary to find several (or the entire set of) effective options. Finding even one compromise option requires a significant amount of computations, while the definition of several (or the entire set of) effective options becomes a problem of exceptional computational complexity.To overcome the computational complexity of multicriteria problems, Professor Strongin’s research team proposed a two-fold approach. First, effective global search algorithms developed within the framework of the information-statistical theory of multi-extremal optimization will be used for solving optimization problems. Second, when performing calculations, all the search information received during the calculation will be used to the greatest possible extent. On the whole, the re-use of search information will result in a continuously decreasing amount of calculation when searching for the next effective options.Computational experiments performed by Lobachevsky University scientists show that the proposed approach makes it possible to reduce more than a hundredfold the amount of required computations when searching for the next effective solution.A good example of practical application of this approach is the optimized profile of railway wheels. This result was obtained jointly with the colleagues from the Technical University of Delft (the Netherlands).”Our calculations show that the proposed optimized profile of train wheels provides an increase in the wheel life to 120 thousand km (more than five times compared with the wheel of the original profile), while increasing the maximum permissible speed from 40 m/sec to 60 m/sec,” notes Professor Strongin. Explore further So it comes as no surprise that researchers at the Lobachevsky University are actively involved in the research of models and methods for making optimal decisions when solving complex problems. A team of scientists under Professor Roman Strongin has proposed a large number of approaches to solving global (multi-extremal) optimization problems, including linear programming of the problems of unconditional optimization, problems of nonlinear programming, and many others.With these approaches, it is possible to solve many problems of optimal decision-making by using some key properties. For example, it is assumed in linear programming problems that all the existing dependencies in the optimization problem are linear. However, existing approaches do not fully cover all possible tasks for making optimal decisions.According to Professor Victor Gergel, a leading member of the research team at the Lobachevsky University, the distinguishing feature of this class of problems is the assumption of multi-extremality of optimized efficiency criteria, for which the optimality among close variants does not necessarily mean the optimality among all possible alternatives.”This determines the complexity of global optimization problems: in order to prove the optimality of the chosen option, one must show that this particular option is the best in the whole range of possible solutions,” says Victor Gergel.At an additional level of complexity, it becomes possible to have several simultaneous performance criteria, which is important in practical applications. In fact, how can engineers choose one quality criterion when developing a new car? Most likely, it is possible to specify several individual partial indicators, such as weight, cost, maximum speed, etc. However, the partial efficiency criteria are, as a rule, contradictory, and no available options would be the best in all respects (the fastest car will not be the cheapest).Therefore, the solution of multicriteria problems is reduced to finding effective compromise options that cannot be improved simultaneously with respect to all the partial criteria. At the same time, it may be necessary in the course of calculations to find several effective solutions. In the extreme case, this may be an entire set of undominated options. Diagonal methods for expensive global optimization In almost any field of human activity, people choose optimal options from a great variety of possible alternatives. When designing new devices, products and systems, researchers and engineers always strive to ensure that their systems have the best characteristics and are economically viable. Thus, for example, a new car being developed must be fast, consume a minimum amount of fuel, be reliable and, in addition, it should not be too expensive. Provided by Lobachevsky University More information: Victor Gergel et al. Efficient multicriterial optimization based on intensive reuse of search information, Journal of Global Optimization (2018). DOI: 10.1007/s10898-018-0624-3 Citation: Effective methods for automated design of complex technical objects and systems (2018, May 21) retrieved 18 July 2019 from https://phys.org/news/2018-05-effective-methods-automated-complex-technical.html
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