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Chimpanzee stool associated circular virus is a single stranded DNA virus isolated from chimpanzee stool. The genome is ~2.6 kilobases in length and encodes two open reading frames (ORFs). The larger of the ORFs encodes the replicase gene and the other the putative capsid protein. A stem-loop and TATA boxes are present in the non coding parts of the sequence. This virus appears to be related to the bovine stool associated circular virus but to no other known group of viruses.
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https://en.wikipedia.org/wiki?curid=33942981
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Bimoment (aka warping moment) is a term used in the analysis of beams (continuum mechanics) that relates to torsion and warping. Its symbol is Mω. show the distributions at a cross-section of (longitudinal) warping stress in cases of torsional warping and distortional warping, respectively. Generally, a bimoment can be represented by a pair of equal and opposite bending moments.
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https://en.wikipedia.org/wiki?curid=33945372
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World tube In physics, a world tube is the path of an object which occupies a nonzero region of space (nonzero volume) at every moment in time, as it travels through 4-dimensional spacetime. That is, as it propagates in spacetime, a world tube traces out a three-dimensional volume for every moment in time. The world tube is analogous to the one-dimensional world line in that it describes the time evolution of an object in space, with the difference that a world line represents the path of a point particle (of nonzero volume), whereas a world tube occupies finite space at all moments in time. A world tube extends beyond the observer in every direction, as it travels from one point to another, allowing to view it as a 4-dimensional map, and a sphere in the 4 dimensions can be described by representing its path in 3-dimensional space. An important difference between two 3-D, one-dimensional world lines is their non-zero boundaries. If there are infinite worlds, a non-zero boundary must exist for every time point between its two corners while none exist for a non-zero one-dimensional world line, since there is a finite distance between each corner of a world line. At that moment in time, the object has been created by a set of events or "unions", corresponding to certain mathematical relations whose expression can be represented within the object's world space
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https://en.wikipedia.org/wiki?curid=33947300
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World tube It is thus analogous to the two-dimensional sphere in that they both describe a three-dimensional volume, which is the boundary of an object between the four-dimensional space to which it has been added and the four-dimensional space the object does not have a corresponding space-velocity along on. The concept of world tube is particularly relevant for special relativity, where a world tube is embedded in Minkowski space.
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https://en.wikipedia.org/wiki?curid=33947300
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Cosmic catastrophe The cosmic catastrophe is a thought experiment in which the sun were to instantaneously disappear. The question is what would then happen to the earth and the other planets orbiting the sun. According to Isaac Newton's classical theory of gravity, the planets would immediately cease to move in circular motion, and inertia would make them start traveling in a straight line. Albert Einstein saw a deficiency in Newton's theory. The finiteness of the speed of light would mean that it would take a certain amount of time before the darkness from the sun's absence would reach the orbiting planet. Therefore, why would the planet instantaneously start traveling in a straight line before the arrival of information that the sun's disappearance has occurred? The cosmic catastrophe thought experiment led Einstein to the invention of the General Theory of Relativity and the creation of the concept of spacetime. Spacetime allowed Einstein to fix the deficiency in Newton's theory. In Einstein's spacetime model, the disappearance of the sun would create gravitational waves in the spacetime. The gravitational waves travel at the speed of light, and an orbiting planet would not react to the sun's disappearance until after the gravitational wave has reached it. Only then, the planet would start to travel in a straight line.
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https://en.wikipedia.org/wiki?curid=33948101
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Melomics (derived from "genomics of melodies") is a computational system for the automatic composition of music (with no human intervention), based on bioinspired algorithms. applies an evolutionary approach to music composition, i.e., music pieces are obtained by simulated evolution. These themes compete to better adapt to a proper fitness function, generally grounded on formal and aesthetic criteria. The system encodes each theme in a genome, and the entire population of music pieces undergoes evo-devo dynamics (i.e., pieces read-out mimicking a complex embryological development process). The system is fully autonomous: once programmed, it composes music without human intervention. This technology has been transferred to industry as an academic spin-off, Media, which has provided and reprogrammed a new computer cluster that created a huge collection of popular music. The results of this evolutionary computation are being stored in Melomics' site, which nowadays constitutes a vast repository of music content. A differentiating feature is that pieces are available in three types of formats: playable (MP3), editable (MIDI and MusicXML) and readable (score in PDF). The computational system includes two computer clusters: Melomics109 and Iamus, dedicated to popular and artistic music, respectively. Melomics109 is cluster programmed and integrated in the system. Its first product is a vast repository of popular music compositions (roughly 1 billion), covering all essential styles
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https://en.wikipedia.org/wiki?curid=33965201
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Melomics In addition to MP3, all songs are available in editable formats (MIDI); and music is licensed under CC0, meaning that it is freely downloadable. 0music is the first album published by Melomics109, which is available in MP3 and MIDI formats, under CC0 license. It has been argued that, by making such amount of editable, original and royalty-free music accessible to people, may accelerate the process of commoditization of music, and change the way music is composed and consumed in the future. In the first stages of the development of the system, Iamus composed "Opus one" (on October 15, 2010), arguably the first fragment of professional contemporary classical music ever composed by a computer in its own style, rather than attempting to emulate the style of existing composers. The first full composition (also in contemporary classic style), "Hello World!", premiered exactly one year after the creation of "Opus one", on October 15, 2011. Four later works premiered on July 2, 2012, and were broadcast live from the School of Computer Science at Universidad de Málaga as part of the events included in the Alan Turing year. The compositions performed at this event were later recorded by the London Symphony Orchestra, creating Iamus' eponymous first album, which New Scientist reported as the "first complete album to be composed solely by a computer and recorded by human musicians
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Melomics " Commenting on the quality and authenticity of the music, Stephen Smoliar, critic of classical music at "The San Francisco Examiner", commented "What is primary is the act of making the music itself engaged by the performers and how the listener responds to what those performers do... what is most interesting about the documents generated by Iamus is their capacity to challenge the creative talents of performing musicians". Melomics' empathic music has been tested in a number of therapeutic clinical trials, evidencing positive effects in reducing fear of heights, acute stress and pain perception. One of the studies resulted in a reduction of almost two thirds of pain perception in children undergoing a standard Skin Prick Test during allergy testing, as compared to the standard procedure. Some of these experiments made use of free mobile apps to adapt music to daily activity, such as jogging, or commuting, but also for therapeutic use, such as lessening stress before an exam, reducing chronic pain, insomnia, and to help children go to sleep. Ongoing efforts to allow to adapt music in real-time to changes in the physiological state of the listener, and to music branding were also reported.
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NGC 3842 is an elliptical galaxy in the constellation of Leo. It was discovered by William Herschel. It is notable for containing one of the largest black holes ever detected, reported to have a mass of 9.7 billion solar masses. It is around 330 million light-years distant from Earth. is the brightest member of the Leo Cluster.
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IFA Tulln The Department für Agrobiotechnology (IFA-Tulln) is one of the 15 departments of the University of Natural Resources and Life Sciences, Vienna (BOKU) operated in cooperation with the Vienna University of Technology and the University of Veterinary Medicine Vienna at the Campus Tulln Technopol. The IFA-Tulln was founded in 1994 as a joint research institution of three major universities in Vienna, the University of Veterinary Medicine Vienna (VetMed), the Vienna University of Technology (TUW) and the University of Natural Resources and Life Sciences Vienna (BOKU). The idea has been to enable the collaboration of scientists with complementary background in the interdisciplinary area of agrobiotechnology under one roof. Their expertise covers modern biotechnology in plant and animal production, environmental biotechnology, animal nutrition, food- and feed science and (bio) analytics and biopolymers. Today about 150 BOKU employees, guest scientists and students are working in 6 institutes at the IFA-Tulln which has become a department of the BOKU in 2004. IFA-Tulln, which is a department of the University of Natural Resources and Life Sciences Vienna (BOKU), was founded in 1994 as a joint research institution of the BOKU, the University of Veterinary Medicine Vienna and the Vienna University of Technology to enable the collaboration of scientists with complementary background in the interdisciplinary area of agrobiotechnology
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IFA Tulln The department is organised into 6 institutes: The first 5 Institutes of the department IFA-Tulln are located in the IFA-Tulln building in Tulln an der Donau on the Campus Tulln Technopol. The sixth Institute (Institute of Animal Nutrition, Products and Nutrition Physiology) is located in Muthgasse, Vienna. The IFA-Tulln building, together with the other working groups of BOKU in the UFT-building (University Research Center Tulln), is forming the “BOKU location Tulln”. Campus Tulln Technopol is part of Technopol Tulln which was founded in 2006 by Ecoplus. Further partners of Technopol Tulln besides BOKU, are: AIT Austrian Institute of Technology, Technopark Tulln GmbH, Technologiezentrum Tulln GmbH, "Agrana Research & Innovation Center", University for Applied Sciences Wiener Neustadt Campus Tulln and the city of Tulln. In its research, the Institute for Biotechnology in Plant Production focuses on basic and applied research in the areas plant breeding, plant genetics and phytopathology. The logical overlaps between these topics are plant-pathogen interaction, genetics of disease resistance and breeding research for disease resistance. The institute almost exclusively performs its own research work on agricultural crop plants. The research focuses on the utilization of natural resources as well as of idle waste material for reinforcements of polymers or for use as thermoplastic matrices. The main processing technologies used in composites- production are extrusion and injection moulding
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IFA Tulln To a lesser content the Institute also applies compression moulding. The Center for Analytical Chemistry (CAC) is aiming to perform cutting edge scientific research and to develop advanced methods in the field of (bio)analytical chemistry. The CAC with its two Christian Doppler Laboratories is pursuing a highly interdisciplinary approach for the determination of chemical contaminants including mycotoxins and allergenic proteins in food. By employing metabolomics based approaches the CAC studies entire biological systems with a special emphasis on plant-fungi interactions. There are five research groups within the Institute: Focus of research activities at the Institute for Environmental Biotechnology is given to the application of microbial metabolism to safeguard the quality of life and preserve natural resources. On the one hand, emphasis is put on degradation or detoxification of pollutants (in soil, water and waste) or the development of monitoring methods to evaluate the success of restoration technologies. On the other hand, the best possible utilization of existing resources by establishment of sustainable material cycles is the central aim of research conducted. Practical application and process development for technical implementation are a primary concern independent from fundamental investigation of the underlying microbiological activities
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IFA Tulln Examples are the scale up of fermentation processes, the development of technical remediation methods and the testing of innovative combined biological-physical processes (e.g. use of membrane bioprocesses) in environmental technology. There are 6 research groups established at the Institute for Environmental Biotechnology: With respect to methodological and research competence at the department the institute for Biotechnology in Animal Production concentrates on advanced tissue culture technologies for the in vitro production of embryos. There are three research groups at the Institute for Biotechnology in Animal Production The Institute of Animal Nutrition, Products, and Nutrition Physiology (APN) represents the start of the supply chain of food of animal origin. It focuses on adequate feeding of agricultural livestock and the significant impact of animal nutrition on quality and safety of primary products, such as milk, meat and eggs. Aside from nutrients, special emphasis is paid on secondary effects of feed and feed/food components on digestion, metabolism and health. The Institute has condensed its mission and structure towards three intrinsic topics: http://www.boku.ac.at/fileadmin/_/H13/Publikationen/Wissensbilanzen/Wissensbilanz_2010/BOKU_Wissensbilanz_2010.pdf
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Life Sciences Foundation (LSF) was a San Francisco-based nonprofit organization that was established in 2011 to collect, preserve, interpret, and promote the history of biotechnology. LSF conducted historical research, maintained archives and published historically relevant materials and information. Their public support of climate-science denier Rep. Dana Rohrabacher in 2018 caused a backlash against the foundation and eroded their scientific credibility. On December 1, 2015, the LSF and the Chemical Heritage Foundation finalized a merger, creating one organization that covers "the history of the life sciences and biotechnology together with the history of the chemical sciences and engineering." As of February 1, 2018, the organization was renamed the Science History Institute, to reflect its wider range of historical interests, from chemical sciences and engineering to the life sciences and biotechnology. The organization is headquartered in Philadelphia but retains offices in the San Francisco Bay area. The LSF mandate was to collect and promote the history of biotechnology. This includes telling the stories of "scientists, inventors, entrepreneurs, managers, executives, and financiers" in order to "humanize" biotechnology to a lay audience. The history of the biotechnology industry includes examining the complex relationships and socio-political dynamics that occur when science and entrepreneurship come together
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Life Sciences Foundation The idea for a foundation that would collect and share the history of biotechnology came about at a meeting in early January 2009 in San Francisco attended by G. Steven Burrill of Burrill & Company, Dennis Gillings of Quintiles in Durham, NC, John Lechleiter of Eli Lilly & Co., Henri Termeer, then CEO of Genzyme and Arnold Thackray, founding President and CEO of the Chemical Heritage Foundation (CHF) Thackray had shaped Chemical Heritage Foundation—"the premier institution preserving the history of chemistry, chemical engineering, and related sciences and technologies." Oral history was one component of the CHF mandate of preserving interpreting, and promoting the history of science. In 1982 the University of Pennsylvania and the American Chemical Society had launched the Center for the History of Chemistry which was renamed the Chemical Heritage Foundation (CHF) in 1992. Thackray, a Fellow of American Academy of Arts and Sciences, the Royal Historical Society and the Royal Society of Chemistry, Thackray received his M.A. and Ph.D. degrees in the history of science from Cambridge University. Thackray argued that before LSF was founded, the recorded history of biotechnology was "fragmented, uneven, and rather paltry." He observed that, "If you don't write your own history, somebody else will do it for you, and they may be hostile
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Life Sciences Foundation " By the end of 2011, LSF's steering committee of industry leaders— Joshua Boger, Robert Carpenter, Bob Coughlin, Henri Termeer and Peter Wirth— were promoting the foundation's work by encouraging scientists and industrialists who were members of the Massachusetts Biotechnology Council, to contribute potential stories and materials to the archival record of the history of biotechnology in Boston and the surrounding region. The conducted oral history interviews with scientists, entrepreneurs, executives, policy makers, and leaders of thought in the biotechnology industry. LSF's hosts timelines, transcripts and audio recordings and provides links to existing oral histories housed at institutions across the globe. Original documentary materials pertinent to the history of biotechnology and the life sciences are being collected. The materials include personal papers and correspondence, donated company records, laboratory notebooks, photographs, video and audio recordings. Collected materials will be guided to permanent repositories in appropriate institutional settings. Electronic reproductions will be made available to scholars, journalists, educators, and the general public in a digital archive. LSF historians work on a range of publications including a quarterly magazine, scholarly articles, white papers, and books
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Life Sciences Foundation These works are intended for multiple audiences and focused on the emergence and evolution of biotechnologies in pharmaceutical discovery and development, agriculture, energy production, and environmental remediation. In October 2011, the University of Chicago Press released "Genentech: The Beginnings of Biotech" by historian Sally Smith Hughes. Founding partners of the include Burrill, Celgene, John Lechleiter, Genentech, Henri Termeer, Merck & Co., Millennium, Pfizer, Quintiles, and Thermo Fisher. MIT professor, Phillip Sharp, serves as LSF's academic advisor. Its executive and advisory board members are leaders from biotech, venture capital, academic institutions and trade associations. When Thackray retired in 2012, Heather R. Erickson, 34, was appointed as LSF President and CEO and member of the Board of Directors. Thackray remained as LSF advisor to its scholarly activities. The Board also includes Brook Byers of Kleiner Perkins Caufield & Byers in Menlo Park, California, Carl B. Feldbaum of Biotechnology Industry Organization (BIO) in Washington, DC who replaced Burrill, Frederick Frank of EVOLUTION Life Science Partners in New York, NY, Gillings in Durham, NC, Lechleiter in Indianapolis, IN, Scott Morrison from San Francisco, CA, Ivor Royston, MD, of Forward Ventures in San Diego, CA, Phillip Sharp from Massachusetts Institute of Technology in Cambridge, MA and Henri Termeer in Cambridge, MA. The first board of directors also included G
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Life Sciences Foundation Steven Burrill, CEO of Burrill & Company— who also published The Journal of Life Sciences and Joshua Boger, former chairman and CEO of Vertex Pharmaceuticals.
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Organ-on-a-chip An organ-on-a-chip (OOC) is a multi-channel 3-D microfluidic cell culture chip that simulates the activities, mechanics and physiological response of entire organs and organ systems, a type of artificial organ. It constitutes the subject matter of significant biomedical engineering research, more precisely in bio-MEMS. The convergence of labs-on-chips (LOCs) and cell biology has permitted the study of human physiology in an organ-specific context, introducing a novel model of in vitro multicellular human organisms. One day, they will perhaps abolish the need for animals in drug development and toxin testing. Although multiple publications claim to have translated organ functions onto this interface, the movement towards this microfluidic application is still in its infancy. Organs-on-chips will vary in design and approach between different researchers. As such, validation and optimization of these systems will likely be a long process. Organs that have been simulated by microfluidic devices include the heart, the lung, kidney, artery, bone, cartilage, skin and more. Nevertheless, building valid artificial organs requires not only a precise cellular manipulation, but a detailed understanding of the human body's fundamental intricate response to any event. A common concern with organs-on-chips lies in the isolation of organs during testing. The body is a complex network of physiological processes, making it challenging to simulate a single organ
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Organ-on-a-chip Microfabrication, microelectronics and microfluidics offer the prospect of modeling sophisticated in vitro physiological responses under accurately simulated conditions. A lab-on-a-chip is a device that integrates one or several laboratory functions on a single chip that deals with handling particles in hollow microfluidic channels. It has been developed for over a decade. Advantages in handling particles at such a small scale include lowering fluid volume consumption (lower reagents costs, less waste), increasing portability of the devices, increasing process control (due to quicker thermo-chemical reactions) and decreasing fabrication costs. Additionally, microfluidic flow is entirely laminar (i.e., no turbulence). Consequently, there is virtually no mixing between neighboring streams in one hollow channel. In cellular biology convergence, this rare property in fluids has been leveraged to better study complex cell behaviors, such as cell motility in response to chemotactic stimuli, stem cell differentiation, axon guidance, subcellular propagation of biochemical signaling and embryonic development. 3D cell-culture models exceed 2D culture systems by promoting higher levels of cell differentiation and tissue organization. 3D culture systems are more successful because the flexibility of the ECM gels accommodates shape changes and cell-cell connections – formerly prohibited by rigid 2D culture substrates
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Organ-on-a-chip Nevertheless, even the best 3D culture models fail to mimic an organ's cellular properties in many aspects, including tissue-to-tissue interfaces (e.g., epithelium and vascular endothelium), spatiotemporal gradients of chemicals, and the mechanically active microenvironments (e.g. arteries’ vasoconstriction and vasodilator responses to temperature differentials). The application of microfluidics in organs-on-chips enables the efficient transport and distribution of nutrients and other soluble cues throughout the viable 3D tissue constructs. Organs-on-chips are referred to as the next wave of 3D cell-culture models that mimic whole living organs’ biological activities, dynamic mechanical properties and biochemical functionalities. Brain-on-a-chip devices create an interface between neuroscience and microfluidics by: 1) improving culture viability; 2) supporting high-throughput screening; 3) modeling organ-level physiology and disease "in vitro/ex vivo", and 4) adding high precision and tunability of microfluidic devices. Brain-on-a-chip devices span multiple levels of complexity in terms of cell culture methodology. Devices have been made using platforms that range from traditional 2D cell culture to 3D tissues in the form of organotypic brain slices. Organotypic brain slices are an "in vitro" model that replicates "in vivo" physiology with additional throughput and optical benefits, thus pairing well with microfluidic devices
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Organ-on-a-chip Brain slices have advantages over primary cell culture in that tissue architecture is preserved and multicellular interactions can still occur. There is flexibility in their use, as slices can be used acutely (less than 6 hours after slice harvesting) or cultured for later experimental use. Because organotypic brain slices can maintain viability for weeks, they allow for long-term effects to be studied. Slice-based systems also provide experimental access with precise control of extracellular environments, making it a suitable platform for correlating disease with neuropathological outcomes. Because approximately 10 to 20 slices can be extracted from a single brain, animal usage is significantly reduced relative to "in vivo" studies. Organotypic brain slices can be extracted and cultured from multiple animal species (e.g. rats), but also from humans. Microfluidic devices have been paired with organotypic slices to improve culture viability. The standard procedure for culturing organotypic brain slices (around 300 microns in thickness) uses semi-porous membranes to create an air-medium interface, but this technique results in diffusion limitations of nutrients and dissolved gases. Because microfluidic systems introduce laminar flow of these necessary nutrients and gases, transport is improved and higher tissue viability can be achieved
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Organ-on-a-chip In addition to keeping standard slices viable, brain-on-a-chip platforms have allowed the successful culturing of thicker brain slices (approximately 700 microns), despite a significant transport barrier due to thickness. As thicker slices retain more native tissue architecture, this allows brain-on-a-chip devices to achieve more “"in vivo"-like” characteristics without sacrificing cell viability. Microfluidic devices support high-throughput screening and toxicological assessments in both 2D and slice cultures, leading to the development of novel therapeutics targeted for the brain. One device was able to screen the drugs Pitavastatin and Irinotecan combinatorically in glioblastoma multiform (the most common form of human brain cancer). These screening approaches have been combined with the modeling of the blood-brain barrier (BBB), a significant hurdle for drugs to overcome when treating the brain, allowing for drug efficacy across this barrier to be studied "in vitro". Microfluidic probes have been used to deliver dyes with high regional precision, making way for localized microperfusion in drug applications. Because microfluidic devices can be designed with optical accessibility, this also allows for the visualization of morphology and processes in specific regions or individual cells
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Organ-on-a-chip Brain-on-a-chip systems can model organ-level physiology in neurological diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis more accurately than with traditional 2D and 3D cell culture techniques. The ability to model these diseases in a way that is indicative of "in vivo" conditions is essential for the translation of therapies and treatments. Additionally, brain-on-a-chip devices have been used for medical diagnostics, such as in biomarker detection for cancer in brain tissue slices. Brain-on-a-chip devices can cause shear stress on cells or tissue due to flow through small channels, which can result in cellular damage. These small channels also introduce susceptibility to the trapping of air bubbles that can disrupt flow and potentially cause damage to the cells. The widespread use of PDMS (Polydimethylsiloxane) in brain-on-a-chip devices has some drawbacks. Although PDMS is cheap, malleable, and transparent, proteins and small molecules can absorb to it and later leech at uncontrolled rates. Lung-on-a-chips are being designed in an effort to improve the physiological relevance of existing in vitro alveolar-capillary interface models. Such a multifunctional microdevice can reproduce key structural, functional and mechanical properties of the human alveolar-capillary interface (i.e., the fundamental functional unit of the living lung)
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Organ-on-a-chip Dongeun Huh from Wyss Institute for Biologically Inspired Engineering at Harvard describes their fabrication of a system containing two closely apposed microchannels separated by a thin (10 µm) porous flexible membrane made of PDMS. The device largely comprises three microfluidic channels, and only the middle one holds the porous membrane. Culture cells were grown on either side of the membrane: human alveolar epithelial cells on one side, and human pulmonary microvascular endothelial cells on the other. The compartmentalization of the channels facilitates not only the flow of air as a fluid which delivers cells and nutrients to the apical surface of the epithelium, but also allows for pressure differences to exist between the middle and side channels. During normal inspiration in a human's respiratory cycle, intrapleural pressure decreases, triggering an expansion of the alveoli. As air is pulled into the lungs, alveolar epithelium and the coupled endothelium in the capillaries are stretched. Since a vacuum is connected to the side channels, a decrease in pressure will cause the middle channel to expand, thus stretching the porous membrane and subsequently, the entire alveolar-capillary interface
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Organ-on-a-chip The pressure-driven dynamic motion behind the stretching of the membrane, also described as a cyclic mechanical strain (valued at approximately 10%), significantly increases the rate of nanoparticle translocation across the porous membrane, when compared to a static version of this device, and to a Transwell culture system. Additionally, researchers believe the potential value of this lung-on-a-chip system will aid in toxicology applications. By investigating the pulmonary response to nanoparticles, researchers hope to learn more about health risks in certain environments, and correct previously oversimplified in vitro models. Because a microfluidic lung-on-a-chip can more exactly reproduce the mechanical properties of a living human lung, its physiological responses will be quicker and more accurate than a Transwell culture system. Nevertheless, published studies admit that responses of a lung-on-a-chip don't yet fully reproduce the responses of native alveolar epithelial cells. Past efforts to replicate in vivo cardiac tissue environments have proven to be challenging due to difficulties when mimicking contractility and electrophysiological responses. Such features would greatly increase the accuracy of in vitro experiments. Microfluidics has already contributed to in vitro experiments on cardiomyocytes, which generate the electrical impulses that control the heart rate
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Organ-on-a-chip For instance, researchers have built an array of PDMS microchambers, aligned with sensors and stimulating electrodes as a tool that will electrochemically and optically monitor the cardiomyocytes’ metabolism. Another lab-on-a-chip similarly combined a microfluidic network in PDMS with planar microelectrodes, this time to measure extracellular potentials from single adult murine cardiomyocytes. A reported design of a heart-on-a-chip claims to have built "an efficient means of measuring structure-function relationships in constructs that replicate the hierarchical tissue architectures of laminar cardiac muscle." This chip determines that the alignment of the myocytes in the contractile apparatus made of cardiac tissue and the gene expression profile (affected by shape and cell structure deformation) contributes to the force produced in cardiac contractility. This heart-on-a-chip is a biohybrid construct: an engineered anisotropic ventricular myocardium is an elastomeric thin film. The design and fabrication process of this particular microfluidic device entails first covering the edges of a glass surface with tape (or any protective film) such as to contour the substrate's desired shape. A spin coat layer of PNIPA is then applied. After its dissolution, the protective film is peeled away, resulting in a self-standing body of PNIPA. The final steps involve the spin coating of protective surface of PDMS over the cover slip and curing
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Organ-on-a-chip Muscular thin films (MTF) enable cardiac muscle monolayers to be engineered on a thin flexible substrate of PDMS. In order to properly seed the 2D cell culture, a microcontact printing technique was used to lay out a fibronectin "brick wall" pattern on the PDMS surface. Once the ventricular myocytes were seeded on the functionalized substrate, the fibronectin pattern oriented them to generate an anisotropic monolayer. After the cutting of the thin films into two rows with rectangular teeth, and subsequent placement of the whole device in a bath, electrodes stimulate the contraction of the myocytes via a field-stimulation – thus curving the strips/teeth in the MTF. Researchers have developed a correlation between tissue stress and the radius of curvature of the MTF strips during the contractile cycle, validating the demonstrated chip as a "platform for quantification of stress, electrophysiology and cellular architecture." Renal cells and nephrons have already been simulated by microfluidic devices. "Such cell cultures can lead to new insights into cell and organ function and be used for drug screening". A kidney-on-a-chip device has the potential to accelerate research encompassing artificial replacement for lost kidney function. Nowadays, dialysis requires patients to go to a clinic up to three times per week
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Organ-on-a-chip A more transportable and accessible form of treatment would not only increase the patient's overall health (by increasing frequency of treatment), but the whole process would become more efficient and tolerable. Artificial kidney research is striving to bring transportability, wearability and perhaps implantation capability to the devices through innovative disciplines: microfluidics, miniaturization and nanotechnology. The nephron is the functional unit of the kidney and is composed of a glomerulus and a tubular component. Researchers at MIT claim to have designed a bioartificial device that replicates the function of the nephron's glomerulus, proximal convoluted tubule and loop of Henle. Each part of the device has its unique design, generally consisting of two microfabricated layers separated by a membrane. The only inlet to the microfluidic device is designed for the entering blood sample. In the glomerulus’ section of the nephron, the membrane allows certain blood particles through its wall of capillary cells, composed by the endothelium, basement membrane and the epithelial podocytes. The fluid that is filtered from the capillary blood into Bowman's space is called filtrate or primary urine. In the tubules, some substances are added to the filtrate as part of the urine formation, and some substances reabsorbed out of the filtrate and back into the blood. The first segment of these tubules is the proximal convoluted tubule
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Organ-on-a-chip This is where the almost complete absorption of nutritionally important substances takes place. In the device, this section is merely a straight channel, but blood particles going to the filtrate have to cross the previously mentioned membrane and a layer of renal proximal tubule cells. The second segment of the tubules is the loop of Henle where the reabsorption of water and ions from the urine takes place. The device's looping channels strives to simulate the countercurrent mechanism of the loop of Henle. Likewise, the loop of Henle requires a number of different cell types because each cell type has distinct transport properties and characteristics. These include the descending limb cells, thin ascending limb cells, thick ascending limb cells, cortical collecting duct cells and medullary collecting duct cells. One step towards validating the microfluidic device's simulation of the full filtration and reabsorption behavior of a physiological nephron would include demonstrating that the transport properties between blood and filtrate are identical with regards to where they occur and what is being let in by the membrane. For example, the large majority of passive transport of water occurs in the proximal tubule and the descending thin limb, or the active transport of NaCl largely occurs in the proximal tubule and the thick ascending limb
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Organ-on-a-chip The device's design requirements would require the filtration fraction in the glomerulus to vary between 15–20%, or the filtration reabsorption in the proximal convoluted tubule to vary between 65–70%, and finally the urea concentration in urine (collected at one of the two outlets of the device) to vary between 200–400 mM. One recent report illustrates a biomimic nephron on hydrogel microfluidic devices with establishing the function of passive diffusion. The complex physiological function of nephron is achieved on the basis of interactions between vessels and tubules (both are hollow channels). However, conventional laboratory techniques usually focus on 2D structures, such as petri-dish that lacks capability to recapitulate real physiology that occurs in 3D. Therefore, the authors developed a new method to fabricate functional, cell-lining and perfusable microchannels inside 3D hydrogel. The vessel endothelial and renal epithelial cells are cultured inside hydrogel microchannel and form cellular coverage to mimic vessels and tubules, respectively. They employed confocal microscope to examine the passive diffusion of one small organic molecule (usually drugs) between the vessels and tubules in hydrogel. The study demonstrates the beneficial potential to mimic renal physiology for regenerative medicine and drug screening. Cardiovascular diseases are often caused by changes in structure and function of small blood vessels
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Organ-on-a-chip For instance, self-reported rates of hypertension suggest that the rate is increasing, says a 2003 report from the National Health and Nutrition Examination Survey. A microfluidic platform simulating the biological response of an artery could not only enable organ-based screens to occur more frequently throughout a drug development trial, but also yield a comprehensive understanding of the underlying mechanisms behind pathologic changes in small arteries and develop better treatment strategies. Axel Gunther from the University of Toronto argues that such MEMS-based devices could potentially help in the assessment of a patient's microvascular status in a clinical setting (personalized medicine). Conventional methods used to examine intrinsic properties of isolated resistance vessels (arterioles and small arteries with diameters varying between 30 µm and 300 µm) include the pressure myography technique. However, such methods currently require manually skilled personnel and are not scalable. An artery-on-a-chip could overcome several of these limitations by accommodating an artery onto a platform which would be scalable, inexpensive and possibly automated in its manufacturing. An organ-based microfluidic platform has been developed as a lab-on-a-chip onto which a fragile blood vessel can be fixed, allowing for determinants of resistance artery malfunctions to be studied. The artery microenvironment is characterized by surrounding temperature, transmural pressure, and luminal & abluminal drug concentrations
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Organ-on-a-chip The multiple inputs from a microenvironment cause a wide range of mechanical or chemical stimuli on the smooth muscle cells (SMCs) and endothelial cells (ECs) that line the vessel's outer and luminal walls, respectively. Endothelial cells are responsible for releasing vasoconstriction and vasodilator factors, thus modifying tone. Vascular tone is defined as the degree of constriction inside a blood vessel relative to its maximum diameter. Pathogenic concepts currently believe that subtle changes to this microenvironment have pronounced effects on arterial tone and can severely alter peripheral vascular resistance. The engineers behind this design believe that a specific strength lies in its ability to control and simulate heterogeneous spatiotemporal influences found within the microenvironment, whereas myography protocols have, by virtue of their design, only established homogeneous microenvironments. They proved that by delivering phenylephrine through only one of the two channels providing superfusion to the outer walls, the drug-facing side constricted much more than the drug opposing side. The artery-on-a-chip is designed for reversible implantation of the sample. The device contains a microchannel network, an artery loading area and a separate artery inspection area
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Organ-on-a-chip There is a microchannel used for loading the artery segment, and when the loading well is sealed, it is also used as a perfusion channel, to replicate the process of nutritive delivery of arterial blood to a capillary bed in the biological tissue. Another pair of microchannels serves to fix the two ends of the arterial segment. Finally, the last pair of microchannels is used to provide superfusion flow rates, in order to maintain the physiological and metabolic activity of the organ by delivering a constant sustaining medium over the abluminal wall. A thermoelectric heater and a thermoresistor are connected to the chip and maintain physiological temperatures at the artery inspection area. The protocol of loading and securing the tissue sample into the inspection zone helps understand how this approach acknowledges whole organ functions. After immersing the tissue segment into the loading well, the loading process is driven by a syringe withdrawing a constant flow rate of buffer solution at the far end of the loading channel. This causes the transport of the artery towards its dedicated position. This is done with closed fixation and superfusion in/outlet lines. After stopping the pump, sub-atmospheric pressure is applied through one of the fixation channels. Then after sealing the loading well shut, the second fixation channel is subjected to a sub-atmospheric pressure. Now the artery is symmetrically established in the inspection area, and a transmural pressure is felt by the segment
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Organ-on-a-chip The remaining channels are opened and constant perfusion and superfusion are adjusted using separate syringe pumps. Vessel-on-chips have been applied to study many disease processes. For example, Alireza Mashaghi and his co-workers developed a model to study viral hemorrhagic syndrome, which involves virus induced vascular integrity loss. The model was used to study Ebola virus disease and to study anti-Ebola drugs. Human skin is the first line of defense against many pathogens and can itself be subject to a variety of diseases and issues, such as cancers and inflammation. As such, skin-on-a-chip (SoC) applications include testing of topical pharmaceuticals and cosmetics, studying the pathology of skin diseases and inflammation, and “creating noninvasive automated cellular assays” to test for the presence of antigens or antibodies that could denote the presence of a pathogen. Despite the wide variety of potential applications, relatively little research has gone into developing a skin-on-a-chip compared to many other organ-on-a-chips, such as lungs and kidneys. Issues such as detachment of the collagen scaffolding from microchannels, incomplete cellular differentiation, and predominant use of poly(dimethysiloxane) (PDMS) for device fabrication, which has been shown to leach chemicals into biological samples and cannot be mass-produced stymie standardization of a platform
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Organ-on-a-chip One additional difficulty is the variability of cell-culture scaffolding, or the base substance in which to culture cells, that is used in skin-on-chip devices. In the human body, this substance is known as the extracellular matrix. The extracellular matrix (ECM) is composed primarily of collagen, and various collagen-based scaffolding has been tested in SoC models. Collagen tends to detach from the microfluidic backbone during culturing due to the contraction of fibroblasts. One study attempted to address this problem by comparing the qualities of collagen scaffolding from three different animal sources: pig skin, rat tail, and duck feet. Other studies also faced detachment issues due to contraction, which can problematic considering that the process of full skin differentiation can take up to several weeks. Contraction issues have been avoided by replacing collagen scaffolding with a fibrin-based dermal matrix, which did not contract. Greater differentiation and formation of cell layers was also reported in microfluidic culture when compared to traditional static culture, agreeing with earlier findings of improved cell-cell and cell-matrix interactions due to dynamic perfusion, or increased permeation through interstitial spaces due to the pressure from continuous media flow
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Organ-on-a-chip This improved differentiation and growth is thought to be in part a product of shear stress created by the pressure gradient along a microchannel due to fluid flow, which may also improve nutrient supply to cells not directly adjacent to the medium. In static cultures, used in traditional skin equivalents, cells receive nutrients in the medium only through diffusion, whereas dynamic perfusion can improve nutrient flow through interstitial spaces, or gaps between cells. This perfusion has also been demonstrated to improve tight junction formation of the "stratum corneum", the tough outer layer of the epidermis, which is the main barrier to penetration of the surface layer of the skin. Dynamic perfusion may also improve cell viability, demonstrated by placing a commercial skin equivalent in a microfluidic platform that extended the expected lifespan by several weeks. This early study also demonstrated the importance of hair follicles in skin equivalent models. Hair follicles are the primary route into the subcutaneous layer for topical creams and other substances applied to the surface of the skin, a feature that more recent studies have often not accounted for. One study developed a SoC consisting of three layers, the epidermis, dermis, and endothelial layer, separated by porous membranes, to study edema, swelling due to extracellular fluid accumulation, a common response to infection or injury and an essential step for cellular repair
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Organ-on-a-chip It was demonstrated that pre-application of Dex, a steroidal cream with anti-inflammatory properties, reduced this swelling in the SoC. Researchers are working towards building a multi-channel 3D microfluidic cell culture system that compartmentalizes microenvironments in which 3D cellular aggregates are cultured to mimic multiple organs in the body. Most organ-on-a-chip models today only culture one cell type, so even though they may be valid models for studying whole organ functions, the systemic effect of a drug on the human body is not verified. In particular, an integrated cell culture analog (µCCA) was developed and included lung cells, drug-metabolizing liver and fat cells. The cells were linked in a 2D fluidic network with culture medium circulating as a blood surrogate, thus efficiently providing a nutritional delivery transport system, while simultaneously removing wastes from the cells. "The development of the µCCA laid the foundation for a realistic in vitro pharmacokinetic model and provided an integrated biomimetic system for culturing multiple cell types with high fidelity to in vivo situations", claim C. Zhang et al. They have developed a microfluidic human-on-a-chip, culturing four different cell types to mimic four human organs: liver, lung, kidney and fat. They focused on developing a standard serum-free culture media that would be valuable to all cell types included in the device
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Organ-on-a-chip Optimized standard media are generally targeted to one specific cell-type, whereas a human-on-a-chip will evidently require a common medium (CM). In fact, they claim to have identified a cell culture CM that, when used to perfuse all cell cultures in the microfluidic device, maintains the cells’ functional levels. Heightening the sensitivity of the in vitro cultured cells ensures the validity of the device, or that any drug injected into the microchannels will stimulate an identical physiological and metabolic reaction from the sample cells as whole organs in humans. With more extensive development of this kind of chip, pharmaceutical companies will potentially be able to measure direct effects of one organ's reaction on another. For instance, the delivery of biochemical substances would be screened to confirm that even though it may benefit one cell type, it does not compromise the functions of others. It is probably already possible to print these organs with 3D printers, but the cost is too high. Designing whole body biomimetic devices addresses a major reservation that pharmaceutical companies have towards organs-on-chips, namely the isolation of organs. As these devices become more and more accessible, the complexity of the design increases exponentially. Systems will soon have to simultaneously provide mechanical perturbation and fluid flow through a circulatory system. "Anything that requires dynamic control rather than just static control is a challenge", says Takayama from the University of Michigan
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Organ-on-a-chip In the early phase of drug development, animal models were the only way of obtaining in vivo data that would predict the human pharmacokinetic responses. However, experiments on animals are lengthy, expensive and controversial. For example, animal models are often subjected to mechanical or chemical techniques that simulate human injuries. There are also concerns with regards to the validity of such animal models, due to deficiency in cross-species extrapolation. Moreover, animal models offer very limited control of individual variables and it can be cumbersome to harvest specific information. Therefore, mimicking a human's physiological responses in an in vitro model needs to be made more affordable, and needs to offer cellular level control in biological experiments: biomimetic microfluidic systems could replace animal testing. The development of MEMS-based biochips that reproduce complex organ-level pathological responses could revolutionize many fields, including toxicology and the developmental process of pharmaceuticals and cosmetics that rely on animal testing and clinical trials. Recently, physiologically based perfusion in vitro systems have been developed to provide cell culture environment close to in vivo cell environment. A new testing platforms based on multi-compartmental perfused systems have gained a remarkable interest in pharmacology and toxicology
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Organ-on-a-chip It aims to provide a cell culture environment close to the in vivo situation to reproduce more reliably "in vivo" mechanisms or ADME processes that involve its absorption, distribution, metabolism, and elimination. Perfused in vitro systems combined with kinetic modelling are promising tools for studying in vitro the different processes involved in the toxicokinetics of xenobiotics. Efforts made toward the development of micro fabricated cell culture systems that aim to create models that replicate aspects of the human body as closely as possible and give examples that demonstrate their potential use in drug development, such as identifying synergistic drug interactions as well as simulating multi-organ metabolic interactions. Multi compartment micro fluidic-based devices, particularly those that are physical representations of physiologically based pharmacokinetic (PBPK) models that represent the mass transfer of compounds in compartmental models of the mammalian body, may contribute to improving the drug development process. Mathematical pharmacokinetic (PK) models aim to estimate concentration-time profiles within each organ on the basis of the initial drug dose. Such mathematical models can be relatively simple, treating the body as a single compartment in which the drug distribution reaches a rapid equilibrium after administration. Mathematical models can be highly accurate when all parameters involved are known
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Organ-on-a-chip Models that combine PK or PBPK models with PD models can predict the time-dependent pharmacological effects of a drug. We can nowadays predict with PBPK models the PK of about any chemical in humans, almost from first principles. These models can be either very simple, like statistical dose-response models, or sophisticated and based on systems biology, according to the goal pursued and the data available. All we need for those models are good parameter values for the molecule of interest. Microfluidic cell culture systems such as micro cell culture analogs (μCCAs) could be used in conjunction with PBPK models. These μCCAs scaled-down devices, termed also body-on-a-chip devices, can simulate multi-tissue interactions under near-physiological fluid flow conditions and with realistic tissue-to-tissue size ratios . Data obtained with these systems may be used to test and refine mechanistic hypotheses. Microfabricating devices also allows us to custom-design them and scale the organs' compartments correctly with respect to one another. Because the device can be used with both animal and human cells, it can facilitate cross-species extrapolation. Used in conjunction with PBPK models, the devices permit an estimation of effective concentrations that can be used for studies with animal models or predict the human response
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Organ-on-a-chip In the development of multicompartment devices, representations of the human body such as those in used PBPK models can be used to guide the device design with regard to the arrangement of chambers and fluidic channel connections to augment the drug development process, resulting in increased success in clinical trials.
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William Compston William (Bill) Compston FAA, FRS (born 19 February 1931) is an Australian geophysicist. He is a Visiting Fellow at the Australian National University. Compston developed the sensitive high-resolution ion microprobe (SHRIMP), for isotopic analyses of geological samples. SHRIMP enabled the world's oldest rock to be identified in Western Australia.
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https://en.wikipedia.org/wiki?curid=33985683
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Megagroove A megagroove is a large scale (kilometres) linear channel eroded through bedrock by the passage of ice, possibly by plucking of the rock at the sides of the channel by the moving ice. They occur in areas of stratified bedrock which are largely free of till, having been identified in the Assynt area of Northwest Scotland, from Michigan and from Ungava and the North West Territories in Canada.
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https://en.wikipedia.org/wiki?curid=34001704
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Three Pagodas Fault The is a right-lateral displacement strike-slip fault between Burma and Thailand named after the Three Pagodas Pass. It developed as a consequence of the collision between the Indian and the Eurasian Plate. The Zone (TPFZ) is a roughly 50 km wide zone separating the westernmost range of the Tenasserim Hills from the Tenasserim coast in Myanmar. The whole area is marked by a great number of fault traces and homoclinal ridges of Paleozoic limestone. The Zone accommodates the southeastward extrusion of Indochina, with stresses twisting clockwise. Together with the Wang Chao Fault and the Mae Ping Fault, it runs parallel to the Red River Fault. There is a fear that a future earthquake caused by the TPFZ and the Sri Sawat Fault Zone (SSFZ) could damage the large dams in Kanchanaburi Province in the future and that it could cause widespread damage to Bangkok. There was already a severe earthquake in the area about 2,500 years ago.
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https://en.wikipedia.org/wiki?curid=34003452
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Yoshio Abe He was the first Japanese scientist to study kinorhynchs, and one such animal, "Dracoderes abei", was named after him. Also named after him was Abe's salamander and Abe's Whiskered Bat, "Myotis abei" Yoshikura 1944, as a tribute from one of his students.
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https://en.wikipedia.org/wiki?curid=34004891
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Peter Dornan Peter John Dornan FRS (born 1939) is a British physicist, and professor at Imperial College London. On 18 September 2009, a festschrift was held in his honor. Awarded the Rutherford Medal and Prize in 2002.
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https://en.wikipedia.org/wiki?curid=34014669
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John Dowell John Derek Dowell FRS (born 6 January 1935) is a British physicist, and emeritus professor at University of Birmingham. He won the 1988 Rutherford Medal and Prize. He was educated at the University of Birmingham (BSc, PhD). In July 2002, a symposium was held in his honor, as he retired in September of that year.
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https://en.wikipedia.org/wiki?curid=34014703
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Stuart Ross Taylor Stuart Ross Taylor, (born 26 November 1925) is a New Zealand-born geochemist and planetary scientist known for his studies of the geology of the Moon through lunar samples, the continental crust, tektites and the evolution of the Solar System. He is an emeritus professor and Visiting Fellow at the Australian National University in Canberra. 5670 Rosstaylor is a main-belt asteroid discovered in 1985.
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https://en.wikipedia.org/wiki?curid=34022917
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Leopold Kober (21 September 1883 – 6 September 1970), an Austrian geologist, proposed a number of (subsequently largely discredited) theories of orogeny and coined the term "kratogen" to describe stable continental crust, which was later shortened to "kraton" by Hans Stille. Kober, developing geosyncline theory, posited that stable blocks known as forelands move toward each other forcing the sediments of the intervening geosynclinal region to move over the forelands and forming marginal mountain ranges known as "Randketten", while leaving an intervening median mass known as the "Zwischengebirge".
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https://en.wikipedia.org/wiki?curid=34035812
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Bovine stool associated circular virus is a single stranded DNA virus with a circular genome that was isolated from bovine stool. This virus was isolated from cows that appeared to be healthy. It has also been isolated from healthy pig stool. The genome is a single stranded circular DNA molecule 2600 bases in length. It has two open reading frames encoding a replicase and capsid protein. The reading frames are arranged in opposite orientations on the genome. A stem loop is present between the 3' ends of the open reading frames. This is like chimpanzee stool associated circular virus and unlike any other known circular DNA virus. This virus appears to form a clade with the chimpanzee stool associated circular virus. Their relationship with other viruses is not yet known. The closest relations appear to be the "Nanoviridae" but further work is required to clarify this point.
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https://en.wikipedia.org/wiki?curid=34049370
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Jaci Antonio Louzada Tupi Caldas (Also signed: "Jacy Antonio Louzada Tupy Caldas", but was best known as "Tupi Caldas".) (19 July 1898 – 1946) was a Brazilian paleontologist. He gave contributions to paleontology describing some of the animals found in the region Paleorrota. He lived in Porto Alegre, was professor of "military school" and a member of the "Historical and Geographical Institute of Rio Grande do Sul", formed in Pharmacy - in 1917 the "Faculty of Medicine of Porto Alegre". In paleontology helped describe "Dinodontosaurus pedroanum" and "Hyperodapedon mariensis".
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https://en.wikipedia.org/wiki?curid=34087137
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Diffuse extragalactic background radiation The diffuse extragalactic background radiation (DEBRA) refers to the diffuse photon field from extragalactic origin that fills our Universe. It contains photons over ∼20 decades of energy from ~10 eV to ~100 GeV. The origin and the physical processes involved are different within every wavelength range. There are plenty of observational evidences that support the existence of the DEBRA. The figure shows a schematic picture, based on many different data sets, of the spectral intensity (also called spectral radiance) multiplied by wavelength of the DEBRA over all the electromagnetic spectrum. This representation is convenient because the area inside the curve is the energy. The nature and history of the universe is coded in this radiation field and any realistic cosmological model must be able to describe it. Understanding the DEBRA is a major challenge of modern cosmology with huge consequences in other fields of astrophysics, therefore extraordinary efforts are being put by theoreticians, observers, and instrumentalists to do so. The overall diffuse extragalactic radiation field may be divided in different regions according to their origin and physical processes involved. This is a standard classification from the highest down to the lowest energies:
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https://en.wikipedia.org/wiki?curid=34115523
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Autotoky is uniparental reproduction by self-fertilization or by parthenogenesis. The word comes from the Greek words "auto" meaning self and "tokos" meaning birth.
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https://en.wikipedia.org/wiki?curid=34133981
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Möwenstein (Ummanz) The Möwenstein is a glacial erratic that was transported south from the area of the present-day island of Bornholm by the ice sheet during the last glaciation. It is located on the island of Ummanz in the west of Rügen within the Western Pomerania Lagoon Area National Park. Erratics are relatively uncommon here, most of them lie east of the island of Rügen. The rock is damaged by boreholes and it is feared that further damage could be caused by frost shattering. The block, which is made of syenogranite and hammer granite, is legally protected as a natural monument and is indexed by the State Office for the Environment, Conservation and Geologie ("") as number G2 91. It is 15.0 metres in circumference and has a volume of about 13.5 m. The Möwenstein lies in the bird reserve immediately next to the dyke near Tankow, and can just be made out from the bird hide. Access to the rock itself is restricted by conservation regulations that depend on the season.
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https://en.wikipedia.org/wiki?curid=34154663
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Siebenschneiderstein The ("Söbenschniedersteen") is a glacial erratic on the island of Rügen. It lies about 22 metres away from the cliffs of "Gellort" on the Baltic Sea beach, one kilometre northwest of Cape Arkona. It has a mass of 165 tonnes and a volume of 61 m³. It belongs, like about 20 other erratics, to the legally protected geotopes on the Island of Rügen. The rock is not the biggest erratic on Rügen (that is the Buskam at 600 m³), but it is the fourth largest and marks the northern point of the island and hence the northernmost point of Eastern Germany.
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Schwanenstein The is a glacial erratic on the island of Rügen in Germany. It lies about 100 metres east of the harbour at Lohme on the northern shore of the Jasmund peninsula about 20 metres off the beach in the Baltic Sea. It weighs 162 tonnes and has a volume of 60 m³. It is thus the fifth largest erratic of about 20 other large glacial boulders that are part of Rügen's legally protected geotopes. It is stylistically portrayed in Lohme's coat of arms. The is made of so-called hammer granite and was very probably transported here from the island of Bornholm during the last ice age. Its reddish appearance is due to the presence of a high proportion of potassium feldspar. On its west side a marked crevice runs through the stone that, over the course of time, has been enlarged by the crystallisation pressure of frozen ice and may well result in the shearing off of a large slab of rock in the near future. Like many other erratics, the is linked to several legends and stories.
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Alexander Tielens Alexander Godfried Gerardus Maria (Xander) Tielens (born 1953) is an astronomer at Leiden Observatory, Leiden University, in the Netherlands. In 2012 he received the highest distinction in Dutch science, the Spinoza Prize. Tielens has contributed significantly to several fields of astronomy, including interstellar physics and astrochemistry. He is mostly known for his work on large aromatic molecules (PAHs) in space and on photodissociation regions. He is also the author of a reference textbook on the interstellar medium. Tielens is the project scientist of the HIFI instrument on board of the Herschel Space Observatory. He used to be the NASA Project Scientist of the Stratospheric Observatory for Infrared Astronomy. Since 2012 Tielens has been a member of the Royal Netherlands Academy of Arts and Sciences.
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Nardevitz Erratic The (), also called the Great Rock of Nardewitz ("Großer Stein von Nardevitz"), is one of the largest glacial erratics in North Germany. It lies about 400 metres north of Nardevitz, a village in the parish of Lohme on the island of Rügen. Surrounded by trees and bushes as well as other drift material that was in the way of farming, it lies in the middle of a field. Its volume is estimated at 104 m³, which gives it a mass of 281 tonnes. The above-ground portion has a volume of 71 m³. It is therefore, apart from Buskam which lies in the Baltic Sea off Göhren, the largest erratic on Rügen and an important geological sight. Because the was used for a long time to obtain construction material, it is suspected today that it was once three times its present size. For example, in 1854 and 1855, column drums weighing about five tonne and pedestal blocks, up to 2 tonnes in weight, for the Prussian Columns near Neukamp and Groß Stresow were hewn from the rock. On the rock itself there are clear traces that show there were plans for further destruction of the erratic. Today the Nardevitz Rock, like around 20 other erratics on the island of Rügen, is one of its legally-protected geotopes. It is recorded in the relevant register at the Mecklenburg-Vorpommern State Office for the Environment, Conservation and Geology ("Landesamt für Umwelt, Naturschutz und Geologie Mecklenburg-Vorpommern") as entry "G2 75"
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Nardevitz Erratic The is made of granite, whose coarse-grained structure corresponds to the hammer granite bedrock found on the island of Bornholm. Its potassium feldspar spars are brownish-grey to pale red and up to 1.5 centimetres across. The up to five millimetre wide quartz crystals have a brownish tinge.
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https://en.wikipedia.org/wiki?curid=34157927
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NGC 7600 is an elliptical galaxy about 160 million light-years in the constellation Aquarius classified as a lenticular galaxy, or, more formally, an S0 galaxy.
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https://en.wikipedia.org/wiki?curid=34171343
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Pure shear In mechanics and geology, pure shear is a three-dimensional homogeneous flattening of a body. It is an example of irrotational strain in which body is elongated in one direction while being shortened perpendicularly. For soft materials, such as rubber, a strain state of pure shear is often used for characterizing hyperelastic and fracture mechanical behaviour. is differentiated from simple shear in that pure shear involves no rigid body rotation. The deformation gradient for pure shear is given by: formula_1 Note that this gives a Green-Lagrange strain of: formula_2 Here there is no rotation occurring, which can be seen from the equal off-diagonal components of the strain tensor. The linear approximation to the Green-Lagrange strain shows that the small strain tensor is: formula_3 which has only shearing components.
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Ryukyu arc The is a volcanic island arc system of Japan's triple junction formed by the subduction of the Philippine Sea Plate beneath the Eurasian Plate between Ryukyu Trench to the south-east and the Okinawa Trough to north-west. It comprises the entirety of the Ryukyu Islands chain. The Ryukyu and Southwest Honshu arcs together form the southwest trending arm of the Boso Triple Junction.
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https://en.wikipedia.org/wiki?curid=34189478
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Allan Hay Allan Stuart Hay FRS (July 23, 1929 – August 14, 2017) was a Canadian chemist, and Tomlinson Emeritus Professor of Chemistry at McGill University. He is best known for his synthesization of Polyphenylene Oxide, leading to the development of Noryl and various other plastics. Hay graduated from the University of Alberta with a B.Sc. in 1950 and an M.Sc. in 1952, and from the University of Illinois at Chicago with a Ph.D. in 1955. He was a research chemist, and manager at General Electric, from 1955 to 1988. In 1975, he became adjunct faculty at the University of Massachusetts Amherst. In 1987, after retiring from GE, he became a research professor of polymer chemistry at McGill University in Montreal, Quebec, Canada. Hay held the GE/NSERC Chair of Polymer Chemistry from 1987 to 1995, and the Tomlinson Chair in Chemistry from 1997 to 2014. He retired from McGill in 2014, returning to Niskayuna, New York. In 1981, Hay was named a fellow of the Royal Society of London. In 1984 he received the IRI Achievement Award from the Industrial Research Institute in recognition for his contributions to science and technology, and society generally, for discoveries in polymerization by oxidative coupling. In 1985 he received the Chemical Pioneer Award from the American Institute of Chemists.
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https://en.wikipedia.org/wiki?curid=34191472
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State Herbarium of South Australia The (sometimes called the South Australian Herbarium, and having the herbarium code, AD) is located in Adelaide, South Australia. It is one of several State and Commonwealth herbaria in Australia. The "Department for Environment and Water" is the state agency which is responsible for the Herbarium, but the "Board of the Botanic Gardens and State Herbarium" (established by an Act of Parliament, most recently the "Botanic Gardens and State Herbarium Act 1978") is charged with its establishment and maintenance. The herbarium is responsible for eFloraSA Electronic Flora of South Australia. It also produces the journal, "Swainsona" (formerly "Journal of the Adelaide Botanic Gardens"). In 1954 the was founded as part of the Adelaide Botanic Garden. The first flora collection of the state was produced by Richard Schomburgk (1811–1891) in 1875. The State Herbarium's collections include collections of Ralph Tate, John McConnell Black (via the South Australian Museum), the moss herbarium of Professor David Guthrie Catcheside (1907–1994), and the collections of the Field Naturalists Society of South Australia. Since 2000 the Herbarium has been located in the historic Tram Barn A building adjacent to the Adelaide Botanic Garden's Bicentennial Conservatory on Hackney Road, Adelaide. In late 2011 the Herbarium was due to list its one millionth specimen, and is currently producing an on-line version of the "Flora of South Australia", 5th edition.
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https://en.wikipedia.org/wiki?curid=34195269
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Vectors in gene therapy Gene therapy utilizes the delivery of DNA into cells, which can be accomplished by several methods, summarized below. The two major classes of methods are those that use recombinant viruses (sometimes called biological nanoparticles or viral vectors) and those that use naked DNA or DNA complexes (non-viral methods). All viruses bind to their hosts and introduce their genetic material into the host cell as part of their replication cycle. This genetic material contains basic 'instructions' of how to produce more copies of these viruses, hacking the body's normal production machinery to serve the needs of the virus. The host cell will carry out these instructions and produce additional copies of the virus, leading to more and more cells becoming infected. Some types of viruses insert their genome into the host's cytoplasm, but do not actually enter the cell. Others penetrate the cell membrane disguised as protein molecules and enter the cell. There are two main types of virus infection: lytic and lysogenic. Shortly after inserting its DNA, viruses of the lytic cycle quickly produce more viruses, burst from the cell and infect more cells. Lysogenic viruses integrate their DNA into the DNA of the host cell and may live in the body for many years before responding to a trigger. The virus reproduces as the cell does and does not inflict bodily harm until it is triggered. The trigger releases the DNA from that of the host and employs it to create new viruses
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Vectors in gene therapy The genetic material in retroviruses is in the form of RNA molecules, while the genetic material of their hosts is in the form of DNA. When a retrovirus infects a host cell, it will introduce its RNA together with some enzymes, namely reverse transcriptase and integrase, into the cell. This RNA molecule from the retrovirus must produce a DNA copy from its RNA molecule before it can be integrated into the genetic material of the host cell. The process of producing a DNA copy from an RNA molecule is termed reverse transcription. It is carried out by one of the enzymes carried in the virus, called reverse transcriptase. After this DNA copy is produced and is free in the nucleus of the host cell, it must be incorporated into the genome of the host cell. That is, it must be inserted into the large DNA molecules in the cell (the chromosomes). This process is done by another enzyme carried in the virus called integrase. Now that the genetic material of the virus has been inserted, it can be said that the host cell has been modified to contain new genes. If this host cell divides later, its descendants will all contain the new genes. Sometimes the genes of the retrovirus do not express their information immediately. One of the problems of gene therapy using retroviruses is that the integrase enzyme can insert the genetic material of the virus into any arbitrary position in the genome of the host; it randomly inserts the genetic material into a chromosome
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Vectors in gene therapy If genetic material happens to be inserted in the middle of one of the original genes of the host cell, this gene will be disrupted (insertional mutagenesis). If the gene happens to be one regulating cell division, uncontrolled cell division (i.e., cancer) can occur. This problem has recently begun to be addressed by utilizing zinc finger nucleases or by including certain sequences such as the beta-globin locus control region to direct the site of integration to specific chromosomal sites. Gene therapy trials using retroviral vectors to treat X-linked severe combined immunodeficiency (X-SCID) represent the most successful application of gene therapy to date. More than twenty patients have been treated in France and Britain, with a high rate of immune system reconstitution observed. Similar trials were restricted or halted in the USA when leukemia was reported in patients treated in the French X-SCID gene therapy trial. To date, four children in the French trial and one in the British trial have developed leukemia as a result of insertional mutagenesis by the retroviral vector. All but one of these children responded well to conventional anti-leukemia treatment. Gene therapy trials to treat SCID due to deficiency of the Adenosine Deaminase (ADA) enzyme (one form of SCID) continue with relative success in the USA, Britain, Ireland, Italy and Japan. Adenoviruses are viruses that carry their genetic material in the form of double-stranded DNA
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Vectors in gene therapy They cause respiratory, intestinal, and eye infections in humans (especially the common cold). When these viruses infect a host cell, they introduce their DNA molecule into the host. The genetic material of the adenoviruses is not incorporated (transient) into the host cell's genetic material. The DNA molecule is left free in the nucleus of the host cell, and the instructions in this extra DNA molecule are transcribed just like any other gene. The only difference is that these extra genes are not replicated when the cell is about to undergo cell division so the descendants of that cell will not have the extra gene. As a result, treatment with the adenovirus will require readministration in a growing cell population although the absence of integration into the host cell's genome should prevent the type of cancer seen in the SCID trials. This vector system has been promoted for treating cancer and indeed the first gene therapy product to be licensed to treat cancer, Gendicine, is an adenovirus. Gendicine, an adenoviral p53-based gene therapy was approved by the Chinese food and drug regulators in 2003 for treatment of head and neck cancer. Advexin, a similar gene therapy approach from Introgen, was turned down by the US Food and Drug Administration (FDA) in 2008. Concerns about the safety of adenovirus vectors were raised after the 1999 death of Jesse Gelsinger while participating in a gene therapy trial. Since then, work using adenovirus vectors has focused on genetically crippled versions of the virus
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Vectors in gene therapy The viral vectors described above have natural host cell populations that they infect most efficiently. Retroviruses have limited natural host cell ranges, and although adenovirus and adeno-associated virus are able to infect a relatively broader range of cells efficiently, some cell types are resistant to infection by these viruses as well. Attachment to and entry into a susceptible cell is mediated by the protein envelope on the surface of a virus. Retroviruses and adeno-associated viruses have a single protein coating their membrane, while adenoviruses are coated with both an envelope protein and fibers that extend away from the surface of the virus. The envelope proteins on each of these viruses bind to cell-surface molecules such as heparin sulfate, which localizes them upon the surface of the potential host, as well as with the specific protein receptor that either induces entry-promoting structural changes in the viral protein, or localizes the virus in endosomes wherein acidification of the lumen induces this refolding of the viral coat. In either case, entry into potential host cells requires a favorable interaction between a protein on the surface of the virus and a protein on the surface of the cell. For the purposes of gene therapy, one might either want to limit or expand the range of cells susceptible to transduction by a gene therapy vector
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Vectors in gene therapy To this end, many vectors have been developed in which the endogenous viral envelope proteins have been replaced by either envelope proteins from other viruses, or by chimeric proteins. Such chimera would consist of those parts of the viral protein necessary for incorporation into the virion as well as sequences meant to interact with specific host cell proteins. Viruses in which the envelope proteins have been replaced as described are referred to as pseudotyped viruses. For example, the most popular retroviral vector for use in gene therapy trials has been the lentivirus Simian immunodeficiency virus coated with the envelope proteins, G-protein, from Vesicular stomatitis virus. This vector is referred to as VSV G-pseudotyped lentivirus, and infects an almost universal set of cells. This tropism is characteristic of the VSV G-protein with which this vector is coated. Many attempts have been made to limit the tropism of viral vectors to one or a few host cell populations. This advance would allow for the systemic administration of a relatively small amount of vector. The potential for off-target cell modification would be limited, and many concerns from the medical community would be alleviated. Most attempts to limit tropism have used chimeric envelope proteins bearing antibody fragments. These vectors show great promise for the development of "magic bullet" gene therapies. A replication-competent vector called ONYX-015 is used in replicating tumor cells
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Vectors in gene therapy It was found that in the absence of the E1B-55Kd viral protein, adenovirus caused very rapid apoptosis of infected, p53(+) cells, and this results in dramatically reduced virus progeny and no subsequent spread. Apoptosis was mainly the result of the ability of EIA to inactivate p300. In p53(-) cells, deletion of E1B 55kd has no consequence in terms of apoptosis, and viral replication is similar to that of wild-type virus, resulting in massive killing of cells. A replication-defective vector deletes some essential genes. These deleted genes are still necessary in the body so they are replaced with either a helper virus or a DNA molecule. Replication-defective vectors always contain a “transfer construct”. The transfer construct carries the gene to be transduced or “transgene”. The transfer construct also carries the sequences which are necessary for the general functioning of the viral genome: packaging sequence, repeats for replication and, when needed, priming of reverse transcription. These are denominated cis-acting elements, because they need to be on the same piece of DNA as the viral genome and the gene of interest. Trans-acting elements are viral elements, which can be encoded on a different DNA molecule. For example, the viral structural proteins can be expressed from a different genetic element than the viral genome. The herpes simplex virus is a human neurotropic virus. This is mostly examined for gene transfer in the nervous system
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Vectors in gene therapy The wild type HSV-1 virus is able to infect neurons and evade the host immune response, but may still become reactivated and produce a lytic cycle of viral replication. Therefore, it is typical to use mutant strains of HSV-1 that are deficient in their ability to replicate. Though the latent virus is not transcriptionally apparent, it does possess neuron specific promoters that can continue to function normally. Antibodies to HSV-1 are common in humans, however complications due to herpes infection are somewhat rare. Caution for rare cases of encephalitis must be taken and this provides some rationale to using HSV-2 as a viral vector as it generally has tropism for neuronal cells innervating the urogenital area of the body and could then spare the host of severe pathology in the brain. Non-viral methods present certain advantages over viral methods, with simple large scale production and low host immunogenicity being just two. Previously, low levels of transfection and expression of the gene held non-viral methods at a disadvantage; however, recent advances in vector technology have yielded molecules and techniques with transfection efficiencies similar to those of viruses. This is the simplest method of non-viral transfection. Clinical trials carried out of intramuscular injection of a naked DNA plasmid have occurred with some success; however, the expression has been very low in comparison to other methods of transfection
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Vectors in gene therapy In addition to trials with plasmids, there have been trials with naked PCR product, which have had similar or greater success. Cellular uptake of naked DNA is generally inefficient. Research efforts focusing on improving the efficiency of naked DNA uptake have yielded several novel methods, such as electroporation, sonoporation, and the use of a "gene gun", which shoots DNA coated gold particles into the cell using high pressure gas. Electroporation is a method that uses short pulses of high voltage to carry DNA across the cell membrane. This shock is thought to cause temporary formation of pores in the cell membrane, allowing DNA molecules to pass through. Electroporation is generally efficient and works across a broad range of cell types. However, a high rate of cell death following electroporation has limited its use, including clinical applications. More recently a newer method of electroporation, termed electron-avalanche transfection, has been used in gene therapy experiments. By using a high-voltage plasma discharge, DNA was efficiently delivered following very short (microsecond) pulses. Compared to electroporation, the technique resulted in greatly increased efficiency and less cellular damage. The use of particle bombardment, or the gene gun, is another physical method of DNA transfection. In this technique, DNA is coated onto gold particles and loaded into a device which generates a force to achieve penetration of the DNA into the cells, leaving the gold behind on a "stopping" disk
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Vectors in gene therapy Sonoporation uses ultrasonic frequencies to deliver DNA into cells. The process of acoustic cavitation is thought to disrupt the cell membrane and allow DNA to move into cells. In a method termed magnetofection, DNA is complexed to magnetic particles, and a magnet is placed underneath the tissue culture dish to bring DNA complexes into contact with a cell monolayer. Hydrodynamic delivery involves rapid injection of a high volume of a solution into vasculature (such as into the inferior vena cava, bile duct, or tail vein). The solution contains molecules that are to be inserted into cells, such as DNA plasmids or siRNA, and transfer of these molecules into cells is assisted by the elevated hydrostatic pressure caused by the high volume of injected solution. The use of synthetic oligonucleotides in gene therapy is to deactivate the genes involved in the disease process. There are several methods by which this is achieved. One strategy uses antisense specific to the target gene to disrupt the transcription of the faulty gene. Another uses small molecules of RNA called siRNA to signal the cell to cleave specific unique sequences in the mRNA transcript of the faulty gene, disrupting translation of the faulty mRNA, and therefore expression of the gene. A further strategy uses double stranded oligodeoxynucleotides as a decoy for the transcription factors that are required to activate the transcription of the target gene
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Vectors in gene therapy The transcription factors bind to the decoys instead of the promoter of the faulty gene, which reduces the transcription of the target gene, lowering expression. Additionally, single stranded DNA oligonucleotides have been used to direct a single base change within a mutant gene. The oligonucleotide is designed to anneal with complementarity to the target gene with the exception of a central base, the target base, which serves as the template base for repair. This technique is referred to as oligonucleotide mediated gene repair, targeted gene repair, or targeted nucleotide alteration. To improve the delivery of the new DNA into the cell, the DNA must be protected from damage and positively charged. Initially, anionic and neutral lipids were used for the construction of lipoplexes for synthetic vectors. However, in spite of the facts that there is little toxicity associated with them, that they are compatible with body fluids and that there was a possibility of adapting them to be tissue specific; they are complicated and time consuming to produce so attention was turned to the cationic versions. Cationic lipids, due to their positive charge, were first used to condense negatively charged DNA molecules so as to facilitate the encapsulation of DNA into liposomes. Later it was found that the use of cationic lipids significantly enhanced the stability of lipoplexes
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Vectors in gene therapy Also as a result of their charge, cationic liposomes interact with the cell membrane, endocytosis was widely believed as the major route by which cells uptake lipoplexes. Endosomes are formed as the results of endocytosis, however, if genes can not be released into cytoplasm by breaking the membrane of endosome, they will be sent to lysosomes where all DNA will be destroyed before they could achieve their functions. It was also found that although cationic lipids themselves could condense and encapsulate DNA into liposomes, the transfection efficiency is very low due to the lack of ability in terms of “endosomal escaping”. However, when helper lipids (usually electroneutral lipids, such as DOPE) were added to form lipoplexes, much higher transfection efficiency was observed. Later on, it was figured out that certain lipids have the ability to destabilize endosomal membranes so as to facilitate the escape of DNA from endosome, therefore those lipids are called fusogenic lipids. Although cationic liposomes have been widely used as an alternative for gene delivery vectors, a dose dependent toxicity of cationic lipids were also observed which could limit their therapeutic usages. The most common use of lipoplexes has been in gene transfer into cancer cells, where the supplied genes have activated tumor suppressor control genes in the cell and decrease the activity of oncogenes. Recent studies have shown lipoplexes to be useful in transfecting respiratory epithelial cells
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Vectors in gene therapy Polymersomes are synthetic versions of liposomes (vesicles with a lipid bilayer), made of amphiphilic block copolymers. They can encapsulate either hydrophilic or hydrophobic contents and can be used to deliver cargo such as DNA, proteins, or drugs to cells. Advantages of polymersomes over liposomes include greater stability, mechanical strength, blood circulation time, and storage capacity. Complexes of polymers with DNA are called polyplexes. Most polyplexes consist of cationic polymers and their fabrication is based on self-assembly by ionic interactions. One important difference between the methods of action of polyplexes and lipoplexes is that polyplexes cannot directly release their DNA load into the cytoplasm. As a result, co-transfection with endosome-lytic agents such as inactivated adenovirus was required to facilitate nanoparticle escape from the endocytic vesicle made during particle uptake. However, a better understanding of the mechanisms by which DNA can escape from endolysosomal pathway, i.e. proton sponge effect, has triggered new polymer synthesis strategies such as incorporation of protonable residues in polymer backbone and has revitalized research on polycation-based systems. Due to their low toxicity, high loading capacity, and ease of fabrication, polycationic nanocarriers demonstrate great promise compared to their rivals such as viral vectors which show high immunogenicity and potential carcinogenicity, and lipid-based vectors which cause dose dependence toxicity
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Vectors in gene therapy Polyethyleneimine and chitosan are among the polymeric carriers that have been extensively studied for development of gene delivery therapeutics. Other polycationic carriers such as poly(beta-amino esters) and polyphosphoramidate are being added to the library of potential gene carriers. In addition to the variety of polymers and copolymers, the ease of controlling the size, shape, surface chemistry of these polymeric nano-carriers gives them an edge in targeting capability and taking advantage of enhanced permeability and retention effect. A dendrimer is a highly branched macromolecule with a spherical shape. The surface of the particle may be functionalized in many ways and many of the properties of the resulting construct are determined by its surface. In particular it is possible to construct a cationic dendrimer, i.e. one with a positive surface charge. When in the presence of genetic material such as DNA or RNA, charge complementarity leads to a temporary association of the nucleic acid with the cationic dendrimer. On reaching its destination the dendrimer-nucleic acid complex is then taken into the cell via endocytosis. In recent years the benchmark for transfection agents has been cationic lipids. Limitations of these competing reagents have been reported to include: the lack of ability to transfect some cell types, the lack of robust active targeting capabilities, incompatibility with animal models, and toxicity
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Vectors in gene therapy Dendrimers offer robust covalent construction and extreme control over molecule structure, and therefore size. Together these give compelling advantages compared to existing approaches. Producing dendrimers has historically been a slow and expensive process consisting of numerous slow reactions, an obstacle that severely curtailed their commercial development. The Michigan-based company Dendritic Nanotechnologies discovered a method to produce dendrimers using kinetically driven chemistry, a process that not only reduced cost by a magnitude of three, but also cut reaction time from over a month to several days. These new "Priostar" dendrimers can be specifically constructed to carry a DNA or RNA payload that transfects cells at a high efficiency with little or no toxicity. Inorganic nanoparticles, such as gold, silica, iron oxide (ex. magnetofection) and calcium phosphates have been shown to be capable of gene delivery. Some of the benefits of inorganic vectors is in their storage stability, low manufacturing cost and often time, low immunogenicity, and resistance to microbial attack. Nanosized materials less than 100 nm have been shown to efficiently trap the DNA or RNA and allows its escape from the endosome without degradation. Inorganics have also been shown to exhibit improved in vitro transfection for attached cell lines due to their increased density and preferential location on the base of the culture dish
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Vectors in gene therapy Quantum dots have also been used successfully and permits the coupling of gene therapy with a stable fluorescence marker. Engineered organic nanoparticles are also under development, which could be used for co-delivery of genes and therapeutic agents. Cell-penetrating peptides (CPPs), also known as peptide transduction domains (PTDs), are short peptides (< 40 amino acids) that efficiently pass through cell membranes while being covalently or non-covalently bound to various molecules, thus facilitating these molecules’ entry into cells. Cell entry occurs primarily by endocytosis but other entry mechanisms also exist. Examples of cargo molecules of CPPs include nucleic acids, liposomes, and drugs of low molecular weight. CPP cargo can be directed into specific cell organelles by incorporating localization sequences into CPP sequences. For example, nuclear localization sequences are commonly used to guide CPP cargo into the nucleus. For guidance into mitochondria, a mitochondrial targeting sequence can be used; this method is used in protofection (a technique that allows for foreign mitochondrial DNA to be inserted into cells' mitochondria). Due to every method of gene transfer having shortcomings, there have been some hybrid methods developed that combine two or more techniques. Virosomes are one example; they combine liposomes with an inactivated HIV or influenza virus. This has been shown to have more efficient gene transfer in respiratory epithelial cells than either viral or liposomal methods alone
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Vectors in gene therapy Other methods involve mixing other viral vectors with cationic lipids or hybridising viruses.
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NGC 3938 is an unbarred spiral galaxy in the Ursa Major constellation. It was discovered on 6 February 1788 by William Herschel. It is one of the brightest spiral galaxies in the Ursa Major South galaxy group, and is roughly 67,000 light years in diameter. It is approximately 43 million light years away from Earth. is classified as type Sc under the Hubble sequence, a loosely wound spiral galaxy with a smaller and dimmer bulge. The spiral arms of the galaxy contain many areas of ionized atomic hydrogen gas, more so towards the center. Two supernovae have been identified within NGC 3938. SN 2005ay is a type II supernova that was discovered on 27 March 2005 and had a magnitude of 15.6. SN 2017ein is a type Ic supernova that was discovered on 25 May 2017 and peaked at magnitude 14.9.
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https://en.wikipedia.org/wiki?curid=34222176
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Electron magnetic circular dichroism (EMCD) (also known as electron energy-loss magnetic chiral dichroism) is the EELS equivalent of XMCD. The effect was first proposed in 2003 and experimentally confirmed in 2006 by the group of Prof. Peter Schattschneider at the Vienna University of Technology. Similarly to XMCD, EMCD is a difference spectrum of two EELS spectra taken in a magnetic field with opposite helicities. Under appropriate scattering conditions virtual photons with specific circular polarizations can be absorbed, giving rise to spectral differences. The largest difference is expected between the case where one virtual photon with left circular polarization and one with right circular polarization are absorbed. By closely analyzing the difference in the EMCD spectrum, information can be obtained on the magnetic properties of the atom, such as its spin and orbital magnetic moment. In the case of transition metals such as iron, cobalt, and nickel, the absorption spectra for EMCD are usually measured at the L-edge. This corresponds to the excitation of a 2p electron to a 3d state by the absorption of a virtual photon providing the ionisation energy. The absorption is visible as a spectral feature in the electron energy loss spectrum (EELS). Because the 3d electron states are the origin of the magnetic properties of the elements, the spectra contain information on the magnetic properties
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Electron magnetic circular dichroism Moreover, since the energy of each transition depends on the atomic number, the information obtained is element specific, that is, it is possible to distinguish the magnetic properties of a given element by examining the EMCD spectrum at its characteristic energy (708 eV for iron). Since in both EMCD and XMCD the same electronic transitions are probed, the information obtained is the same. However EMCD has a higher spatial resolution and depth sensitivity than its X-ray counterpart. Moreover, EMCD can be measured on any TEM equipped with an EELS detector, whereas XMCD is normally measured only on dedicated synchrotron beamlines. It has been recently demonstrated that electron vortex beams can be also used to measure EMCD.
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https://en.wikipedia.org/wiki?curid=34227089
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Francisco Aranda Millán (14 October 1881, Villarroya de la Sierra – 20 July 1937) was a Spanish zoologist. He was executed during the Spanish Civil War by a fascist squadron in Valdemorillo. He was the father of film critic and Surrealist author Jose Francisco Aranda (1925-1989).
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Carlos Ameghino Carlos Ciriaco Ameghino (16 June 1865 – 12 April 1936) was an Argentine paleontologist and explorer who accompanied his brother Florentino Ameghino throughout Argentina searching for fossils. was educated as a naturalist with his brother Florentino Ameghino on his journeys to Buenos Aires and the Chaco Province in Argentina. The goal of this expedition was to collect fossils. In 1887, he decided to explore South Argentina, and the watersheds of the Santa Cruz River, the Chubut River, the Chico River, the Deseado River, the Gallegos River, and the Straits of Megellan. He discovered many fossils and created several geological and paleontological reports in his research that he gave to his brother. He also demonstrated the exact superposition of two great tertiary formations.
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https://en.wikipedia.org/wiki?curid=34227237
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Bel–Robinson tensor In general relativity and differential geometry, the is a tensor defined in the abstract index notation by: Alternatively, where formula_3 is the Weyl tensor. It was introduced by Lluís Bel in 1959. The is constructed from the Weyl tensor in a manner analogous to the way the electromagnetic stress–energy tensor is built from the electromagnetic tensor. Like the electromagnetic stress–energy tensor, the is totally symmetric and traceless: In general relativity, there is no unique definition of the local energy of the gravitational field. The is a possible definition for local energy, since it can be shown that whenever the Ricci tensor vanishes (i.e. in vacuum), the is divergence-free:
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Buoyant density centrifugation (also isopycnic centrifugation or equilibrium density-gradient centrifugation) uses the concept of buoyancy to separate molecules in solution by their differences in density. Historically a caesium chloride (CsCl) solution was often used, but more commonly used density gradients are sucrose or Percoll. The sample is put on top of the solution, and then the tube is spun at a very high speed for an extended time, at times lasting days. The CsCl molecules become densely packed toward the bottom, so even layers of different densities form. Since the original solution was approximately the same density, they go to a level where their density and the CsCl density are the same, to which they form a sharp, distinctive band. This method very sharply separates molecules, and is so sharp that it can even separate different molecular isotopes from one another. Buoyant density of majority of DNA is 1.7g/cm3 which is equal to density of 6M CsCl solution. Buoyant density of DNA changes with its GC content.
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Peeling theorem In general relativity, the peeling theorem describes the asymptotic behavior of the Weyl tensor as one goes to null infinity. Let formula_1 be a null geodesic in a spacetime formula_2 from a point p to null infinity, with affine parameter formula_3. Then the theorem states that, as formula_3 tends to infinity: where formula_6 is the Weyl tensor, and we used the abstract index notation. Moreover, in the Petrov classification, formula_7 is type N, formula_8 is type III, formula_9 is type II (or II-II) and formula_10 is type I.
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Synge's world function In general relativity, is an example of a bitensor, i.e. a tensorial function of pairs of points in the spacetime. Let formula_1 be two points in spacetime, and suppose formula_2 belongs to a convex normal neighborhood of formula_2 so that there exists a unique geodesic formula_4 from formula_2 to formula_6, up to the affine parameter formula_7. Suppose formula_8 and formula_9. Then is defined as: where formula_11 is the tangent vector to the affinely parametrized geodesic formula_4. That is, formula_13 is half the square of the geodesic length from formula_2 to formula_6. is well-defined, since the integral above is invariant under reparametrization. In particular, for Minkowski spacetime, the simplifies to half the spacetime interval between the two points:
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Geroch's splitting theorem In the theory of causal structure on Lorentzian manifolds, Geroch's theorem or (first proved by Robert Geroch) gives a topological characterization of globally hyperbolic spacetimes. Let formula_1 be a globally hyperbolic spacetime. Then formula_1 is strongly causal and there exists a global "time function" on the manifold, i.e. a continuous, surjective map formula_3 such that: Moreover, all Cauchy surfaces are homeomorphic, and formula_7 is homeomorphic to formula_8 where formula_9 is any Cauchy surface of formula_7.
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Billietite is an uncommon mineral of Uranium that contains Barium. It has the chemical formula: Ba(UO)O(OH)•8HO. It usually occurs as clear yellow orthorhombic crystals. is named after Valere Louis Billiet (1903–1944), Belgian crystallographer at the University of Ghent, Ghent, Belgium.
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Vanuralite is a mineral of uranium with chemical formula: Al(UO)(VO)(OH)·11(HO). It has yellow crystals and a Mohs hardness of 2. The name comes from the composition of the mineral.
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https://en.wikipedia.org/wiki?curid=34267749
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Francesco Ambrosi (November 17, 1821 – 9 April 1897) was an Italian botanist, librarian ethnologue and historian.
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https://en.wikipedia.org/wiki?curid=34268685
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Henry Nathaniel Andrews Henry Nathaniel Andrews, Jr. (born June 15, 1910, Melrose, Massachusetts; d. March 3, 2002 Concord, New Hampshire) was an American paleobotanist recognized as an expert in plants of the Devonian and Carboniferous periods. He was a fellow of the Geological Society of America and the American Association for the Advancement of Science and was elected into the U.S. National Academy of Sciences in 1975. He was a professor at the Washington University in St. Louis from 1940 to 1964 and a paleobotanist at the Missouri Botanical Garden 1947 to 1964. From 1964 until his retirement 1975, Andrews worked at the University of Connecticut, where he served as head of the school's Botany department and later as head of the Systematics and Environmental Section.
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https://en.wikipedia.org/wiki?curid=34270521
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Pearl vortex In superconductivity, a is a vortex of supercurrent in a thin film of type-II superconductor, first described in 1964 by Judea Pearl. A is similar to Abrikosov vortex except for its magnetic field profile which, due to the dominant air-metal interface, diverges sharply as 1/formula_1 at short distances from the center, and decays slowly, like 1/formula_2 at long distances. Abrikosov's vortices, in comparison, have very short range interaction and diverge as formula_3 near the center. A transport current flowing through a superconducting film may cause these vortices to move with a constant velocity formula_4 proportional to, and perpendicular to the transport current. Because of their proximity to the surface, and their sharp field divergence at their centers, Pearl's vortices can actually be seen by a scanning SQUID microscope. The characteristic length governing the distribution of the magnetic field around the vortex center is given by the ratio formula_5/formula_6, also known as "Pearl length," where formula_6 is the film thickness and formula_8 is London penetration depth. Because this ratio can reach macroscopic dimensions (~1 mm) by making the film sufficiently thin, it can be measured relatively easy and used to estimate the density of superconducting electrons. At distances shorter than the Pearl's length, vortices behave like a Coulomb gas (1/formula_1 repulsive force).
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https://en.wikipedia.org/wiki?curid=34271702
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NGC 5562 is a spiral galaxy (class S) in the constellation of Boötes.
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https://en.wikipedia.org/wiki?curid=34289623
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Gavino Gulia (1835–1889) was a Maltese botanist and author of books on flora of that island.
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https://en.wikipedia.org/wiki?curid=34296447
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