2,986 research outputs found

    Decadal link between longitudinal morphological changes in branching channels of Yangtze Estuary and movement of the offshore depo-center

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    In estuaries, the morphology of inland and offshore areas usually evolves synergistically. This study examines the decadal link between longitudinal changes in morphology of branching channels and movement of the offshore depo-center (where sediment deposition rate is maximum) of the Yangtze River estuary, under intense human interference. Integrated data analysis is provided on morphology, runoff discharge, and ebb partition ratio from 1950 to 2017. Channel-volume reductions and change rates between isobaths in branching channels reflect the impact of estuarine engineering projects. Ebb partition ratio and duration of discharge ≥ 60 000 m3 s-1 act as proxies for the water excavating force in branching channels and runoff intensity. It is found that deposition occurs in the lower/upper sub-reaches (or further downstream/upstream channels) of the inland north/south branching channels, and the offshore depo-center moves southward or southeastward, as runoff intensity grows; the reverse occurs as runoff intensity declines. This is because the horizontal circumfluence in the Yangtze estuary rotates clockwise as ebb partition ratios of the north/south branching channels increase/decrease for increasing runoff, and conversely rotates anticlockwise for decreasing runoff. Land reclamation activities, the Deepwater Channel Project, and the Qingcaosha Reservoir have impacted greatly on longitudinal changes of morphology in the North Branch and the South Passage and on ebb partition ratio variations in the North/South Channel and the North/South Passage. Dam-induced runoff flattening has enhanced deposition in the upper/lower sub-reaches of the north/south branching channels and caused northward movement of the offshore depo-center, except in areas affected by estuarine engineering projects. Dam-induced longitudinal evolution of branching channel morphology and offshore depo-center movement will likely persist in the future, given the ongoing construction of large cascade dams in the upper Yangtze and the completion of major projects in the Yangtze estuary

    A conceptual exoskeleton shoulder design for the assistance of upper limb movement

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    © Springer International Publishing AG, part of Springer Nature 2018. There is an increased interest on wearable technologies for rehabilitation and human augmentation. Systems focusing on the upper limbs are attempting to replicate the musculoskeletal structures found in humans, reproducing existing behaviors and capabilities. The current work is expanding on existing systems with a novel design that ensures the maximum range of motion while at the same time allowing for lockable features ensuring higher manipulation payloads at minimum energy and fatigue costs. An analysis of the biomechanics of the shoulder is being done and a detailed system design for structural as well actuation elements of a parallel mechanism is given. The benefits for the use are discussed of reduced weight, maximum range of motion at minimum energy cost

    Modelling generalized firms' restructuring using inverse DEA

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    The key consideration for firms’ restructuring is improving their operational efficiencies. Market conditions often offer opportunities or generate threats that can be handled by restructuring scenarios through consolidation, to create synergy, or through split, to create reverse synergy. A generalized restructuring refers to a move in a business market where a homogeneous set of firms, a set of pre-restructuring decision making units (DMUs), proceed with a restructuring to produce a new set of post-restructuring entities in the same market to realize efficiency targets. This paper aims to develop a novel inverse Data Envelopment Analysis based methodology, called GInvDEA (Generalized Inverse DEA), for modeling the generalized restructuring. Moreover, the paper suggests a linear programming model that allows determining the lowest performance levels, measured by efficiency that can be achieved through a given generalized restructuring. An application in banking operations illustrates the theory developed in the paper

    Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations

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    PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036

    Tube Formation in Nanoscale Materials

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    The formation of tubular nanostructures normally requires layered, anisotropic, or pseudo-layered crystal structures, while inorganic compounds typically do not possess such structures, inorganic nanotubes thus have been a hot topic in the past decade. In this article, we review recent research activities on nanotubes fabrication and focus on three novel synthetic strategies for generating nanotubes from inorganic materials that do not have a layered structure. Specifically, thermal oxidation method based on gas–solid reaction to porous CuO nanotubes has been successfully established, semiconductor ZnS and Nb2O5nanotubes have been prepared by employing sacrificial template strategy based on liquid–solid reaction, and an in situ template method has been developed for the preparation of ZnO taper tubes through a chemical etching reaction. We have described the nanotube formation processes and illustrated the detailed key factors during their growth. The proposed mechanisms are presented for nanotube fabrication and the important pioneering studies are discussed on the rational design and fabrication of functional materials with tubular structures. It is the intention of this contribution to provide a brief account of these research activities

    Matched pairs of human prostate stromal cells display differential tropic effects on LNCaP prostate cancer cells

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    Prostate stromal cells may play binary roles in the process of prostate cancer development. As the first to be encountered by infiltrating prostate cancer cells, prostate stromal cells form the first defense line against prostate cancer progression and metastasis. However, interaction between prostate cancer and stromal cells may facilitate the formation of a tumor microenvironment favoring cancer cell growth and survival. To establish an experimental system for studying the interaction between cancer and stromal cells, we isolated three matched pairs of normal and cancer-associated human prostate stromal clones. In this report, we describe the morphologic and behavioral characteristics of these cells and their effect on LNCaP prostate cancer cells in co-culture. Unlike LNCaP prostate cancer cells, the isolated prostate stromal clones are large fibroblast-like cells with a slow proliferation rate. Growth and survival of these clones are not affected by androgens. The stromal cells display high resistance to serum starvation, while cancer-associated stromal clones have differentiated survival ability. In co-culture experiments, the stromal cells protected some LNCaP prostate cancer cells from death by serum starvation, and cancer-associated stromal clones showed more protection. This work thus established a panel of valuable human prostate stromal cell lines, which could be used in co-culture to study the interaction between prostate cancer and prostate stromal cells

    Multilevel Deconstruction of the In Vivo Behavior of Looped DNA-Protein Complexes

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    Protein-DNA complexes with loops play a fundamental role in a wide variety of cellular processes, ranging from the regulation of DNA transcription to telomere maintenance. As ubiquitous as they are, their precise in vivo properties and their integration into the cellular function still remain largely unexplored. Here, we present a multilevel approach that efficiently connects in both directions molecular properties with cell physiology and use it to characterize the molecular properties of the looped DNA-lac repressor complex while functioning in vivo. The properties we uncover include the presence of two representative conformations of the complex, the stabilization of one conformation by DNA architectural proteins, and precise values of the underlying twisting elastic constants and bending free energies. Incorporation of all this molecular information into gene-regulation models reveals an unprecedented versatility of looped DNA-protein complexes at shaping the properties of gene expression.Comment: Open Access article available at http://www.plosone.org/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.000035

    2-Hydroxyglutarate Production, but Not Dominant Negative Function, Is Conferred by Glioma-Derived NADP+-Dependent Isocitrate Dehydrogenase Mutations

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    Gliomas frequently contain mutations in the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase (IDH1) or the mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2). Several different amino acid substitutions recur at either IDH1 R132 or IDH2 R172 in glioma patients. Genetic evidence indicates that these mutations share a common gain of function, but it is unclear whether the shared function is dominant negative activity, neomorphic production of (R)-2-hydroxyglutarate (2HG), or both.We show by coprecipitation that five cancer-derived IDH1 R132 mutants bind IDH1-WT but that three cancer-derived IDH2 R172 mutants exert minimal binding to IDH2-WT. None of the mutants dominant-negatively lower isocitrate dehydrogenase activity at physiological (40 µM) isocitrate concentrations in mammalian cell lysates. In contrast to this, all of these mutants confer 10- to 100-fold higher 2HG production to cells, and glioma tissues containing IDH1 R132 or IDH2 R172 mutations contain high levels of 2HG compared to glioma tissues without IDH mutations (54.4 vs. 0.1 mg 2HG/g protein).Binding to, or dominant inhibition of, WT IDH1 or IDH2 is not a shared feature of the IDH1 and IDH2 mutations, and thus is not likely to be important in cancer. The fact that the gain of the enzymatic activity to produce 2HG is a shared feature of the IDH1 and IDH2 mutations suggests that this is an important function for these mutants in driving cancer pathogenesis

    The Interstellar Medium In Galaxies Seen A Billion Years After The Big Bang

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    Evolution in the measured rest frame ultraviolet spectral slope and ultraviolet to optical flux ratios indicate a rapid evolution in the dust obscuration of galaxies during the first 3 billion years of cosmic time (z>4). This evolution implies a change in the average interstellar medium properties, but the measurements are systematically uncertain due to untested assumptions, and the inability to measure heavily obscured regions of the galaxies. Previous attempts to directly measure the interstellar medium in normal galaxies at these redshifts have failed for a number of reasons with one notable exception. Here we report measurements of the [CII] gas and dust emission in 9 typical (~1-4L*) star-forming galaxies ~1 billon years after the big bang (z~5-6). We find these galaxies have >12x less thermal emission compared with similar systems ~2 billion years later, and enhanced [CII] emission relative to the far-infrared continuum, confirming a strong evolution in the interstellar medium properties in the early universe. The gas is distributed over scales of 1-8 kpc, and shows diverse dynamics within the sample. These results are consistent with early galaxies having significantly less dust than typical galaxies seen at z<3 and being comparable to local low-metallicity systems.Comment: Submitted to Nature, under review after referee report. 22 pages, 4 figures, 4 Extended Data Figures, 5 Extended Data table
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