904 resultados para electromechanical response mechanisms


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Aberrant DNA replication, defects in the protection, and restart of stalled replication forks are major causes of genome instability in all organisms. Replication fork reversal is emerging as an evolutionarily conserved physiological response for restart of stalled forks. Escherichia coli RecG, RuvAB, and RecA proteins have been shown to reverse the model replication fork structures in vitro. However, the pathways and the mechanisms by which Mycobacterium tuberculosis, a slow growing human pathogen, responds to different types of replication stress and DNA damage are unclear. Here, we show that M. tuberculosis RecG rescues E. coli Delta recG cells from replicative stress. The purified M. tuberculosis RecG (MtRecG) and RuvAB(MtRuvAB) proteins catalyze fork reversal of model replication fork structures with and without a leading strand single-stranded DNA gap. Interestingly, single-stranded DNA-binding protein suppresses the MtRecG- and MtRuvAB-mediated fork reversal with substrates that contain lagging strand gap. Notably, our comparative studies with fork structures containing template damage and template switching mechanism of lesion bypass reveal that MtRecG but not MtRuvAB or MtRecA is proficient in driving the fork reversal. Finally, unlike MtRuvAB, we find that MtRecG drives efficient reversal of forks when fork structures are tightly bound by protein. These results provide direct evidence and valuable insights into the underlying mechanism of MtRecG-catalyzed replication fork remodeling and restart pathways in vivo.

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How do we assess the capability of a compliant mechanism of given topology and shape? The kinetoelastostatic maps proposed in this paper help answer this question. These maps are drawn in 2D using two non-dimensional quantities, one capturing the nonlinear static response and the other the geometry, material, and applied forces. Geometrically nonlinear finite element analysis is used to create the maps for compliant mechanisms consisting of slender beams. In addition to the topology and shape, the overall proportions and the proportions of the cross-sections of the beam segments are kept fixed for a map. The finite region of the map is parameterized using a non-dimensional quantity defined as the slenderness ratio. The shape and size of the map and the parameterized curves inside it indicate the complete kinetoelastostatic capability of the corresponding compliant mechanism of given topology, shape, and fixed proportions. Static responses considered in this paper include input/output displacement, geometric amplification, mechanical advantage, maximum stress, etc. The maps can be used to compare mechanisms, to choose a suitable mechanism for an application, or re-design as may be needed. The usefulness of the non-dimensional maps is presented with multiple applications of different variety. Non-dimensional portrayal of snap-through mechanisms is one such example. The effect of the shape of the cross-section of the beam segments and the role of different segments in the mechanism as well as extension to 3D compliant mechanisms, the cases of multiple inputs and outputs, and moment loads are also explained. The effects of disproportionate changes on the maps are also analyzed.

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Heterogeneous photocatalysis is an ideal green energy technology for the purification of wastewater. Although titania dominates as the reference photocatalyst, its wide band gap is a bottleneck for extended utility. Thus, search for non-TiO2 based nanomaterials has become an active area of research in recent years. In this regard, visible light absorbing polycrystalline WO3 (2.4-2.8 eV) and Bi2WO6 (2.8 eV) with versatile structure-electronic properties has gained considerable interest to promote the photocatalytic reactions. These materials are also explored in selective functional group transformation in organic reactions, because of low reduction and oxidation potential of WO3 CB and Bi2WO6 VB, respectively. In this focused review, various strategies such as foreign ion doping, noble metal deposition and heterostructuring with other semiconductors designed for efficient photocatalysis is discussed. These modifications not only extend the optical response to longer wavelengths, but also prolong the life-time of the charge carriers and strengthen the photocatalyst stability. The changes in the surface-bulk properties and the charge carrier transfer dynamics associated with each modification correlating to the high activity are emphasized. The presence of oxidizing agents, surface modification with Cu2+ ions and synthesis of exposed facets to promote the degradation rate is highlighted. In depth study on these nanomaterials is likely to sustain interest in wastewater remediation and envisaged to signify in various green energy applications. (C) 2015 Elsevier B.V. All rights reserved.

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Objectives:To determine if there is a biological mechanism that explains the association between HIV disease progression and increased mortality with low circulating vitamin D levels; specifically, to determine if restoring vitamin D levels induced T-cell functional changes important for antiviral immunity.Design:This was a pilot, open-label, three-arm prospective phase 1 study.Methods:We recruited 28 patients with low plasma vitamin D (<50nmol/l 25-hydroxyvitamin D3), comprising 17 HIV+ patients (11 on HAART, six treatment-naive) and 11 healthy controls, who received a single dose of 200000IU oral cholecalciferol. Advanced T-cell flow cytometry methods measured CD4(+) T-cell function associated with viral control in blood samples at baseline and 1-month after vitamin D supplementation.Results:One month of vitamin D supplementation restored plasma levels to sufficiency (>75nmol/l) in 27 of 28 patients, with no safety issues. The most striking change was in HIV+ HAART+ patients, where increased frequencies of antigen-specific T cells expressing macrophage inflammatory protein (MIP)-1 - an important anti-HIV blocking chemokine - were observed, with a concomitant increase in plasma MIP-1, both of which correlated significantly with vitamin D levels. In addition, plasma cathelicidin - a vitamin D response gene with broad antimicrobial activity - was enhanced.Conclusion:Vitamin D supplementation modulates disease-relevant T-cell functions in HIV-infected patients, and may represent a useful adjunct to HAART therapy. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.

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The Load-Unload Response Ratio (LURR) method is an intermediate-term earthquake prediction approach that has shown considerable promise. It involves calculating the ratio of a specified energy release measure during loading and unloading where loading and unloading periods are determined from the earth tide induced perturbations in the Coulomb Failure Stress on optimally oriented faults. In the lead-up to large earthquakes, high LURR values are frequently observed a few months or years prior to the event. These signals may have a similar origin to the observed accelerating seismic moment release (AMR) prior to many large earthquakes or may be due to critical sensitivity of the crust when a large earthquake is imminent. As a first step towards studying the underlying physical mechanism for the LURR observations, numerical studies are conducted using the particle based lattice solid model (LSM) to determine whether LURR observations can be reproduced. The model is initialized as a heterogeneous 2-D block made up of random-sized particles bonded by elastic-brittle links. The system is subjected to uniaxial compression from rigid driving plates on the upper and lower edges of the model. Experiments are conducted using both strain and stress control to load the plates. A sinusoidal stress perturbation is added to the gradual compressional loading to simulate loading and unloading cycles and LURR is calculated. The results reproduce signals similar to those observed in earthquake prediction practice with a high LURR value followed by a sudden drop prior to macroscopic failure of the sample. The results suggest that LURR provides a good predictor for catastrophic failure in elastic-brittle systems and motivate further research to study the underlying physical mechanisms and statistical properties of high LURR values. The results provide encouragement for earthquake prediction research and the use of advanced simulation models to probe the physics of earthquakes.

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The creep response of metallic foam sandwich beams in 3-point bend is investigated numerically for the case of a metallic foam core and two steel faces. The face sheets are treated as elastic, while the foam core is modeled by a viscoplastic extension of the Deshpande-Fleck yield surface. This power-law creeping constitutive law has been implemented within the commercial finite element code ABAQUS. It is found that the beams creep by a variety of competing mechanisms, depending upon the choice of material properties and the geometric parameters. A failure map is constructed and effect of rate dependence on the load-deflection curves is quantified, and compared against the available experimental data.

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The objective of the article is to present a unified model for the dynamic mechanical response of ceramics under compressive stress states. The model incorporates three principal deformation mechanisms: (i) lattice plasticity due to dislocation glide or twinning; (ii) microcrack extension; and (iii) granular flow of densely packed comminuted particles. In addition to analytical descriptions of each mechanism, prescriptions are provided for their implementation into a finite element code as well as schemes for mechanism transitions. The utility of the code in addressing issues pertaining to deep penetration is demonstrated through a series of calculations of dynamic cavity expansion in an infinite medium. The results reveal two limiting behavioral regimes, dictated largely by the ratio of the cavity pressure p to the material yield strength σY. At low values of p/σY, cavity expansion occurs by lattice plasticity and hence its rate diminishes with increasing σY. In contrast, at high values, expansion occurs by microcracking followed by granular plasticity and is therefore independent of σY. In the intermediate regime, the cavity expansion rate is governed by the interplay between microcracking and lattice plasticity. That is, when lattice plasticity is activated ahead of the expanding cavity, the stress triaxiality decreases (toward more negative values) which, in turn, reduces the propensity for microcracking and the rate of granular flow. The implications for penetration resistance to high-velocity projectiles are discussed. Finally, the constitutive model is used to simulate the quasi-static and dynamic indentation response of a typical engineering ceramic (alumina) and the results compared to experimental measurements. Some of the pertinent observations are shown to be captured by the present model whereas others require alternative approaches (such as those based on fracture mechanics) for complete characterization. © 2011 The American Ceramic Society.

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In situ compressive tests on specially designed small samples made from brittle metallic foams were accomplished in a loading device equipped in the scanning electron microscopy (SEM). Each of the small samples comprises only several cells in the effective test zone (ETZ), with one major cell in the middle. In such a system one can not only obtain sequential collapse-process images of a single cell and its cell walls with high resolution, but also correlate the detailed failure behaviour of the cell walls with the stress-strain response, therefore reveal the mechanisms of energy absorption in the mesoscopic scale. Meanwhile, the stress-strain behaviour is quite different from that of bulk foams in dimensions of enough large, indicating a strong size effect. According to the in situ observations, four failure modes in the cell-wall level were summarized, and these modes account for the mesoscopic mechanisms of energy absorption. Paralleled compression tests on bulk samples were also carried out, and it is found that both fracturing of a single cell and developing of fracture bands are defect-directed or weakness-directed processes. The mechanical properties of the brittle aluminum foams obtained from the present tests agree well with the size effect model for ductile cellular solids proposed by Onck et al. (C) 2008 Elsevier Ltd. All rights reserved.

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EXECUTIVE SUMMARY 1. DECADAL-SCALE CLIMATE EVENTS 1.1 Introduction 1.2 Basin-scale Patterns 1.3 Long Time Series in the North Pacific 1.4 Decadal Climate Variability in Ecological Regions of the North Pacific 1.5 Mechanisms 1.6 References 2. COHERENT REGIONAL RESPONSES 2.1 Introduction 2.2 Central North Pacific (CNP) 2.3 California Current System (CCS) 2.4 Gulf of Alaska (GOA) 2.5 Bering Sea and Aleutian Islands 2.6 Western North Pacific (WNP) 2.7 Coherence in Regional Responses to the 1998 Regime Shift 2.8 Climate Indicators for Detecting Regime Shifts 2.9 References 3. IMPLICATIONS FOR THE MANAGEMENT OF MARINE RESOURCES 3.1 Introduction 3.2 Response Time of Biota to Regime Shifts 3.3 Response Time of Management to Regime Shifts 3.4 Provision of Stock Assessment Advice 3.5 Decision Rules 3.6 References 4. SUGGESTED LITERATURE 4.1 Climate Regimes 4.2 Impacts on Lower Trophic Levels 4.3 Impacts on Fish and Higher Trophic Levels 4.4 Impacts on Ecosystems and Possible Mechanisms 4.5 Regimes and Fisheries Management APPENDIX 1: RECENT ECOSYSTEM CHANGES IN THE CENTRAL NORTH PACIFIC A1.1 Introduction A1.2 Physical Oceanography A1.3 Lower Trophic Levels A1.4 Invertebrates A1.5 Fishes A1.6 References APPENDIX 2: RECENT ECOSYSTEM CHANGES IN THE CALIFORNIA CURRENT SYSTEM A2.1 Introduction A2.2 Physical Oceanography A2.3 Lower Trophic Levels A2.4 Invertebrates A2.5 Fishes A2.6 References APPENDIX 3: RECENT ECOSYSTEM CHANGES IN THE GULF OF ALASKA A3.1 Introduction A3.2 Physical Oceanography A3.3 Lower Trophic Levels A3.4 Invertebrates A3.5 Fishes A3.6 Higher Trophic Levels A3.7 Coherence in Gulf of Alaska Fish A3.8 Combined Standardized Indices of Recruitment and Survival Rate A3.9 References APPENDIX 4: RECENT ECOSYSTEM CHANGES IN THE BERING SEA AND ALEUTIAN ISLANDS A4.1 Introduction A4.2 Bering Sea Environmental Variables and Physical Oceanography A4.3 Bering Sea Lower Trophic Levels A4.4 Bering Sea Invertebrates A4.5 Bering Sea Fishes A4.6 Bering Sea Higher Trophic Levels A4.7 Coherence in Bering Sea Fish Responses A4.8 Combined Standardized Indices of Bering Fish Recruitment and Survival Rate A4.9 Aleutian Islands A4.10 References APPENDIX 5: RECENT ECOSYSTEM CHANGES IN THE WESTERN NORTH PACIFIC A5.1 Introduction A5.2 Sea of Okhotsk A5.3 Tsushima Current Region and Kuroshio/Oyashio Current Region A5.4 Bohai Sea, Yellow Sea, and East China Sea A5.5 References (168 page document)

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Cells in the lateral intraparietal cortex (LIP) of rhesus macaques respond vigorously and in spatially-tuned fashion to briefly memorized visual stimuli. Responses to stimulus presentation, memory maintenance, and task completion are seen, in varying combination from neuron to neuron. To help elucidate this functional segmentation a new system for simultaneous recording from multiple neighboring neurons was developed. The two parts of this dissertation discuss the technical achievements and scientific discoveries, respectively.

Technology. Simultanous recordings from multiple neighboring neurons were made with four-wire bundle electrodes, or tetrodes, which were adapted to the awake behaving primate preparation. Signals from these electrodes were partitionable into a background process with a 1/f-like spectrum and foreground spiking activity spanning 300-6000 Hz. Continuous voltage recordings were sorted into spike trains using a state-of-the-art clustering algorithm, producing a mean of 3 cells per site. The algorithm classified 96% of spikes correctly when tetrode recordings were confirmed with simultaneous intracellular signals. Recording locations were verified with a new technique that creates electrolytic lesions visible in magnetic resonance imaging, eliminating the need for histological processing. In anticipation of future multi-tetrode work, the chronic chamber microdrive, a device for long-term tetrode delivery, was developed.

Science. Simultaneously recorded neighboring LIP neurons were found to have similar preferred targets in the memory saccade paradigm, but dissimilar peristimulus time histograms, PSTH). A majority of neighboring cell pairs had a difference in preferred directions of under 45° while the trial time of maximal response showed a broader distribution, suggesting homogeneity of tuning with het erogeneity of function. A continuum of response characteristics was present, rather than a set of specific response types; however, a mapping experiment suggests this may be because a given cell's PSTH changes shape as well as amplitude through the response field. Spike train autocovariance was tuned over target and changed through trial epoch, suggesting different mechanisms during memory versus background periods. Mean frequency-domain spike-to-spike coherence was concentrated below 50 Hz with a significant maximum of 0.08; mean time-domain coherence had a narrow peak in the range ±10 ms with a significant maximum of 0.03. Time-domain coherence was found to be untuned for short lags (10 ms), but significantly tuned at larger lags (50 ms).

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Nucleic acids are most commonly associated with the genetic code, transcription and gene expression. Recently, interest has grown in engineering nucleic acids for biological applications such as controlling or detecting gene expression. The natural presence and functionality of nucleic acids within living organisms coupled with their thermodynamic properties of base-pairing make them ideal for interfacing (and possibly altering) biological systems. We use engineered small conditional RNA or DNA (scRNA, scDNA, respectively) molecules to control and detect gene expression. Three novel systems are presented: two for conditional down-regulation of gene expression via RNA interference (RNAi) and a third system for simultaneous sensitive detection of multiple RNAs using labeled scRNAs.

RNAi is a powerful tool to study genetic circuits by knocking down a gene of interest. RNAi executes the logic: If gene Y is detected, silence gene Y. The fact that detection and silencing are restricted to the same gene means that RNAi is constitutively on. This poses a significant limitation when spatiotemporal control is needed. In this work, we engineered small nucleic acid molecules that execute the logic: If mRNA X is detected, form a Dicer substrate that targets independent mRNA Y for silencing. This is a step towards implementing the logic of conditional RNAi: If gene X is detected, silence gene Y. We use scRNAs and scDNAs to engineer signal transduction cascades that produce an RNAi effector molecule in response to hybridization to a nucleic acid target X. The first mechanism is solely based on hybridization cascades and uses scRNAs to produce a double-stranded RNA (dsRNA) Dicer substrate against target gene Y. The second mechanism is based on hybridization of scDNAs to detect a nucleic acid target and produce a template for transcription of a short hairpin RNA (shRNA) Dicer substrate against target gene Y. Test-tube studies for both mechanisms demonstrate that the output Dicer substrate is produced predominantly in the presence of a correct input target and is cleaved by Dicer to produce a small interfering RNA (siRNA). Both output products can lead to gene knockdown in tissue culture. To date, signal transduction is not observed in cells; possible reasons are explored.

Signal transduction cascades are composed of multiple scRNAs (or scDNAs). The need to study multiple molecules simultaneously has motivated the development of a highly sensitive method for multiplexed northern blots. The core technology of our system is the utilization of a hybridization chain reaction (HCR) of scRNAs as the detection signal for a northern blot. To achieve multiplexing (simultaneous detection of multiple genes), we use fluorescently tagged scRNAs. Moreover, by using radioactive labeling of scRNAs, the system exhibits a five-fold increase, compared to the literature, in detection sensitivity. Sensitive multiplexed northern blot detection provides an avenue for exploring the fate of scRNAs and scDNAs in tissue culture.

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Humans are particularly adept at modifying their behavior in accordance with changing environmental demands. Through various mechanisms of cognitive control, individuals are able to tailor actions to fit complex short- and long-term goals. The research described in this thesis uses functional magnetic resonance imaging to characterize the neural correlates of cognitive control at two levels of complexity: response inhibition and self-control in intertemporal choice. First, we examined changes in neural response associated with increased experience and skill in response inhibition; successful response inhibition was associated with decreased neural response over time in the right ventrolateral prefrontal cortex, a region widely implicated in cognitive control, providing evidence for increased neural efficiency with learned automaticity. We also examined a more abstract form of cognitive control using intertemporal choice. In two experiments, we identified putative neural substrates for individual differences in temporal discounting, or the tendency to prefer immediate to delayed rewards. Using dynamic causal models, we characterized the neural circuit between ventromedial prefrontal cortex, an area involved in valuation, and dorsolateral prefrontal cortex, a region implicated in self-control in intertemporal and dietary choice, and found that connectivity from dorsolateral prefrontal cortex to ventromedial prefrontal cortex increases at the time of choice, particularly when delayed rewards are chosen. Moreover, estimates of the strength of connectivity predicted out-of-sample individual rates of temporal discounting, suggesting a neurocomputational mechanism for variation in the ability to delay gratification. Next, we interrogated the hypothesis that individual differences in temporal discounting are in part explained by the ability to imagine future reward outcomes. Using a novel paradigm, we imaged neural response during the imagining of primary rewards, and identified negative correlations between activity in regions associated the processing of both real and imagined rewards (lateral orbitofrontal cortex and ventromedial prefrontal cortex, respectively) and the individual temporal discounting parameters estimated in the previous experiment. These data suggest that individuals who are better able to represent reward outcomes neurally are less susceptible to temporal discounting. Together, these findings provide further insight into role of the prefrontal cortex in implementing cognitive control, and propose neurobiological substrates for individual variation.

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The signal recognition particle (SRP) targets membrane and secretory proteins to their correct cellular destination with remarkably high fidelity. Previous studies have shown that multiple checkpoints exist within this targeting pathway that allows ‘correct cargo’ to be quickly and efficiently targeted and for ‘incorrect cargo’ to be promptly rejected. In this work, we delved further into understanding the mechanisms of how substrates are selected or discarded by the SRP. First, we discovered the role of the SRP fingerloop and how it activates the SRP and SRP receptor (SR) GTPases to target and unload cargo in response to signal sequence binding. Second, we learned how an ‘avoidance signal’ found in the bacterial autotransporter, EspP, allows this protein to escape the SRP pathway by causing the SRP and SR to form a ‘distorted’ complex that is inefficient in delivering the cargo to the membrane. Lastly, we determined how Trigger Factor, a co-translational chaperone, helps SRP discriminate against ‘incorrect cargo’ at three distinct stages: SRP binding to RNC; targeting of RNC to the membrane via SRP-FtsY assembly; and stronger antagonism of SRP targeting of ribosomes bearing nascent polypeptides that exceed a critical length. Overall, results delineate the rich underlying mechanisms by which SRP recognizes its substrates, which in turn activates the targeting pathway and provides a conceptual foundation to understand how timely and accurate selection of substrates is achieved by this protein targeting machinery.

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Advances in nano-scale mechanical testing have brought about progress in the understanding of physical phenomena in materials and a measure of control in the fabrication of novel materials. In contrast to bulk materials that display size-invariant mechanical properties, sub-micron metallic samples show a critical dependence on sample size. The strength of nano-scale single crystalline metals is well-described by a power-law function, σαD-n, where D is a critical sample size and n is a experimentally-fit positive exponent. This relationship is attributed to source-driven plasticity and demonstrates a strengthening as the decreasing sample size begins to limit the size and number of dislocation sources. A full understanding of this size-dependence is complicated by the presence of microstructural features such as interfaces that can compete with the dominant dislocation-based deformation mechanisms. In this thesis, the effects of microstructural features such as grain boundaries and anisotropic crystallinity on nano-scale metals are investigated through uniaxial compression testing. We find that nano-sized Cu covered by a hard coating displays a Bauschinger effect and the emergence of this behavior can be explained through a simple dislocation-based analytic model. Al nano-pillars containing a single vertically-oriented coincident site lattice grain boundary are found to show similar deformation to single-crystalline nano-pillars with slip traces passing through the grain boundary. With increasing tilt angle of the grain boundary from the pillar axis, we observe a transition from dislocation-dominated deformation to grain boundary sliding. Crystallites are observed to shear along the grain boundary and molecular dynamics simulations reveal a mechanism of atomic migration that accommodates boundary sliding. We conclude with an analysis of the effects of inherent crystal anisotropy and alloying on the mechanical behavior of the Mg alloy, AZ31. Through comparison to pure Mg, we show that the size effect dominates the strength of samples below 10 μm, that differences in the size effect between hexagonal slip systems is due to the inherent crystal anisotropy, suggesting that the fundamental mechanism of the size effect in these slip systems is the same.