Under conditions of hypoxia, most eukaryotic cells can shift their primary metabolic strategy from predominantly mitochondrial respiration towards increased glycolysis to maintain ATP levels. This ...hypoxia‐induced reprogramming of metabolism is key to satisfying cellular energetic requirements during acute hypoxic stress. At a transcriptional level, this metabolic switch can be regulated by several pathways including the hypoxia inducible factor‐1α (HIF‐1α) which induces an increased expression of glycolytic enzymes. While this increase in glycolytic flux is beneficial for maintaining bioenergetic homeostasis during hypoxia, the pathways mediating this increase can also be exploited by cancer cells to promote tumour survival and growth, an area which has been extensively studied. It has recently become appreciated that increased glycolytic metabolism in hypoxia may also have profound effects on cellular physiology in hypoxic immune and endothelial cells. Therefore, understanding the mechanisms central to mediating this reprogramming are of importance from both physiological and pathophysiological standpoints. In this review, we highlight the role of HIF‐1α in the regulation of hypoxic glycolysis and its implications for physiological processes such as angiogenesis and immune cell effector function.
figure legend Schematic outlining the functional physiological consequences of enhanced glycolytic metabolism in endothelial cells and immune cells.
Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological immunological niches. The impact of ...hypoxia on immunity and inflammation can vary depending on the microenvironment and immune processes occurring in a given niche. In physiological immunological niches, such as the bone marrow, lymphoid tissue, placenta and intestinal mucosa, physiological hypoxia controls innate and adaptive immunity by modulating immune cell proliferation, development and effector function, largely via transcriptional changes driven by hypoxia-inducible factor (HIF). By contrast, in pathological immunological niches, such as tumours and chronically inflamed, infected or ischaemic tissues, pathological hypoxia can drive tissue dysfunction and disease development through immune cell dysregulation. Here, we differentiate between the effects of physiological and pathological hypoxia on immune cells and the consequences for immunity and inflammation in different immunological niches. Furthermore, we discuss the possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease.
In this brief, the output reachable estimation and safety verification problems for multilayer perceptron (MLP) neural networks are addressed. First, a conception called maximum sensitivity is ...introduced, and for a class of MLPs whose activation functions are monotonic functions, the maximum sensitivity can be computed via solving convex optimization problems. Then, using a simulation-based method, the output reachable set estimation problem for neural networks is formulated into a chain of optimization problems. Finally, an automated safety verification is developed based on the output reachable set estimation result. An application to the safety verification for a robotic arm model with two joints is presented to show the effectiveness of the proposed approaches.
Power electronics-intensive dc microgrids use increasingly complex software-based controllers and communication networks. They are evolving into cyber-physical systems (CPS) with sophisticated ...interactions between physical and computational processes, making them vulnerable to cyber attacks. This paper presents a framework to detect possible false-data injection attacks (FDIAs) in cyber-physical dc microgrids. The detection problem is formalized as identifying a change in sets of inferred candidate invariants. Invariants are microgrids properties that do not change over time. Both the physical plant and the software controller of CPS can be described as Simulink/Stateflow (SLSF) diagrams. The dynamic analysis infers the candidate invariants over the input/output variables of SLSF components. The reachability analysis generates the sets of reachable states (reach sets) for the CPS modeled as hybrid automata. The candidate invariants that contain the reach sets are called the actual invariants. The candidate invariants are then compared with the actual invariants, and any mismatch indicates the presence of FDIA. To evaluate the proposed methodology, the hybrid automaton of a dc microgrid, with a distributed cooperative control scheme, is presented. The reachability analysis is performed to obtain the reach sets and, hence, the actual invariants. Moreover, a prototype tool, HYbrid iNvariant GEneratoR, is extended to instrument SLSF models, obtain candidate invariants, and identify FDIA.
Ethnography and Virtual Worldsis the only book of its kind--a concise, comprehensive, and practical guide for students, teachers, designers, and scholars interested in using ethnographic methods to ...study online virtual worlds, including both game and nongame environments. Written by leading ethnographers of virtual worlds, and focusing on the key method of participant observation, the book provides invaluable advice, tips, guidelines, and principles to aid researchers through every stage of a project, from choosing an online fieldsite to writing and publishing the results.
Provides practical and detailed techniques for ethnographic research customized to reflect the specific issues of online virtual worlds, both game and nongame Draws on research in a range of virtual worlds, including Everquest, Second Life, There.com, and World of Warcraft Provides suggestions for dealing with institutional review boards, human subjects protocols, and ethical issues Guides the reader through the full trajectory of ethnographic research, from research design to data collection, data analysis, and writing up and publishing research results Addresses myths and misunderstandings about ethnographic research, and argues for the scientific value of ethnography
Radionuclide renal scintigraphy provides important functional data to assist in the diagnosis and management of patients with a variety of suspected genitourinary tract problems, but the procedures ...are underutilized. Maximizing the utility of the available studies (as well as the perception of utility by referring physicians) requires a clear understanding of the clinical question, attention to quality control, acquisition of the essential elements necessary to produce an informed interpretation, and production of a report that presents a coherent impression that specifically addresses the clinical question and is supported by data contained in the report. To help achieve these goals, part 1 of this review covers information that should be provided to the patient before the scan, describes the advantages and limitations of the available radiopharmaceuticals, discusses quality control elements needed to optimize the study, summarizes approaches to the measurements of renal function, and focuses on recommended quantitative indices and their diagnostic applications. Although the primary focus is the adult patient, aspects of the review also apply to the pediatric population.
Originating from the early 1970s in Luleå, Sweden, and initially designed for the agricultural industry, hot-stamped sheet steel has developed to become the leading material in a modern ...state-of-the-art lightweight structural automotive body engineering. This critical review provides a detailed insight into the origins, fundamental metallurgical principles, commercial growth, current legal stronghold on aluminising coatings and latest technological developments. Comparisons to other state-of–the-art ferrous and non-ferrous automotive sheet materials are made, including carbon fibre-reinforced polymer; while the future outlook for hot-stamped sheet steel and opportunities for further technological developments are highlighted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
► This paper shows that the Bayh-Dole Act has had a major impact on scientist entrepreneurship, measured as the propensity for scientists to start a new firm. ► It shows that scientists who are on a ...board of a company or scientific advisory board, and publish frequently with scientists employed in industry have a greater propensity to engage in entrepreneurial activity.
Much of the literature examining the impact of the Bayh-Dole Act has been based on the impact on patenting and licensing activities emanating from offices of technology transfer. Studies based on data generated by offices of technology transfer, suggest a paucity of entrepreneurial activity from university scientists in the form on new startups. There are, however, compelling reasons to suspect that the TTO generated data may not measure all, or even most of scientist entrepreneurship. Rather than relying on measures of scientist entrepreneurship reported by the TTO and compiled by AUTM, this study instead develops alternative measures based on the commercialization activities reported by scientists. In particular, the purpose of this paper is to provide a measure of scientist entrepreneurship and identify which factors are conducive to scientist entrepreneurship and which factors inhibit scientist entrepreneurship. This enables us to compare how scientist entrepreneurship differs from that which has been established in the literature for the more general population. We do this by developing a new database measuring the propensity of scientists funded by grants from the National Cancer Institute (NCI) to commercialize their research as well as the mode of commercialization. We then subject this new university scientist-based data set to empirical scrutiny to ascertain which factors influence both the propensity for scientists to become an entrepreneur. The results suggest that scientist entrepreneurship may be considerably more robust than has generally been indicated in studies based on TTO data.
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