192 research outputs found

    Barrier-controlled carrier transport in microcrystalline semiconducting materials: Description within a unified model

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    A recently developed model that unifies the ballistic and diffusive transport mechanisms is applied in a theoretical study of carrier transport across potential barriers at grain boundaries in microcrystalline semiconducting materials. In the unified model, the conductance depends on the detailed structure of the band edge profile and in a nonlinear way on the carrier mean free path. Equilibrium band edge profiles are calculated within the trapping model for samples made up of a linear chain of identical grains. Quantum corrections allowing for tunneling are included in the calculation of electron mobilities. The dependence of the mobilities on carrier mean free path, grain length, number of grains, and temperature is examined, and appreciable departures from the results of the thermionic-field-emission model are found. Specifically, the unified model is applied in an analysis of Hall mobility data for n-type microcrystalline Si thin films in the range of thermally activated transport. Owing mainly to the effect of tunneling, potential barrier heights derived from the data are substantially larger than the activation energies of the Hall mobilities. The specific features of the unified model, however, cannot be resolved within the rather large uncertainties of the analysis.Comment: REVTex, 19 pages, 9 figures; to appear in J. Appl. Phy

    Interior of a Schwarzschild black hole revisited

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    The Schwarzschild solution has played a fundamental conceptual role in general relativity, and beyond, for instance, regarding event horizons, spacetime singularities and aspects of quantum field theory in curved spacetimes. However, one still encounters the existence of misconceptions and a certain ambiguity inherent in the Schwarzschild solution in the literature. By taking into account the point of view of an observer in the interior of the event horizon, one verifies that new conceptual difficulties arise. In this work, besides providing a very brief pedagogical review, we further analyze the interior Schwarzschild black hole solution. Firstly, by deducing the interior metric by considering time-dependent metric coefficients, the interior region is analyzed without the prejudices inherited from the exterior geometry. We also pay close attention to several respective cosmological interpretations, and briefly address some of the difficulties associated to spacetime singularities. Secondly, we deduce the conserved quantities of null and timelike geodesics, and discuss several particular cases in some detail. Thirdly, we examine the Eddington-Finkelstein and Kruskal coordinates directly from the interior solution. In concluding, it is important to emphasize that the interior structure of realistic black holes has not been satisfactorily determined, and is still open to considerable debate.Comment: 15 pages, 7 figures, Revtex4. V2: Version to appear in Foundations of Physic

    Unsuitability of the moving light clock system for the Lorentz factor derivation

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    The moving light clock system was analyzed with respect to the orientation of the wavefront of the light pulse observed in the moving and stationary frames of reference. The plane wavefront of the light pulse was oriented horizontally in both the frames. The wavefront observed in the stationary frame was not perpendicular to the direction of the light pulse propagation. This showed different characteristics of the light pulse than that assumed in the Lorentz factor derivation. According to the horizontal orientation of the wavefront, velocity c was determined as the vertical component of the light pulse motion observed in the stationary frame. Application of this velocity distribution in the Lorentz factor derivation showed the same travel time for the light pulse observed in the moving and stationary frames of reference. The moving light clock system was therefore found to be unsuitable for the Lorentz factor derivation and illustration of time dilation, and shown to illustrate the relativity of the observation of light rather than the relativity of time.Comment: 4 pages, 5 figure

    Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

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    A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

    Lesson from the Stoichiometry Determination of the Cohesin Complex: A Short Protease Mediated Elution Increases the Recovery from Cross-Linked Antibody-Conjugated Beads

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    Affinity purification of proteins using antibodies coupled to beads and subsequent mass spectrometric analysis has become a standard technique for the identification of protein complexes. With the recent transfer of the isotope dilution mass spectrometry principle (IDMS) to the field of proteomics, quantitative analysesssuch as the stoichiometry determination of protein complexesshave become achievable. Traditionally proteins were eluted from antibody-conjugated beads using glycine at low pH or using diluted acids such as HCl, TFA, or FA, but elution was often found to be incomplete. Using the cohesin complex and the anaphase promoting complex/cyclosome (APC/C) as examples, we show that a short 15-60 min predigestion with a protease such as LysC (modified on-bead digest termed protease elution) increases the elution efficiency 2- to 3-fold compared to standard acid elution protocols. While longer incubation periodssas performed in standard on-bead digestionsled to partial proteolysis of the cross-linked antibodies, no or only insignificant cleavage was observed after 15-60 min protease mediated elution. Using the protease elution method, we successfully determined the stoichiometry of the cohesin complex by absolute quantification of the four core subunits using LC-SRM analysis and 19 reference peptides generated with the EtEP strategy. Protease elution was 3-fold more efficient compared to HCl elution, but measurements using both elution techniques are in agreement with

    Nonmotorized Recreation and Motorized Recreation in Shrub-Steppe Habitats Affects Behavior and Reproduction of Golden Eagles (\u3cem\u3eAquila Chrysaetos\u3c/em\u3e)

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    Different forms of outdoor recreation have different spatiotemporal activity patterns that may have interactive or cumulative effects on wildlife through human disturbance, physical habitat change, or both. In western North America, shrub-steppe habitats near urban areas are popular sites for motorized recreation and nonmotorized recreation and can provide important habitat for protected species, including golden eagles. Our objective was to determine whether recreation use (i.e., number of recreationists) or recreation features (e.g., trails or campsites) predicted golden eagle territory occupancy, egg-laying, or the probability a breeding attempt resulted in ≥1 offspring (nest survival). We monitored egg-laying, hatching and fledging success, eagle behavior, and recreation activity within 23 eagle territories near Boise, Idaho, USA. Territories with more off-road vehicle (ORV) use were less likely to be occupied than territories with less ORV use (β = −1.6, 85% CI: −2.8 to −0.8). At occupied territories, early season pedestrian use (β = −1.6, 85% CI: −3.8 to −0.2) and other nonmotorized use (β = −3.6, 85% CI: −10.7 to −0.3) reduced the probability of egg-laying. At territories where eagles laid eggs, short, interval-specific peaks in ORV use were associated with decreased nest survival (β = −0.5, 85% CI: −0.8 to −0.2). Pedestrians, who often arrived near eagle nests via motorized vehicles, were associated with reduced nest attendance (β = −11.9, 85% CI: −19.2 to −4.5), an important predictor of nest survival. Multiple forms of recreation may have cumulative effects on local populations by reducing occupancy at otherwise suitable territories, decreasing breeding attempts, and causing nesting failure. Seasonal no-stopping zones for motorized vehicles may be an alternative to trail closures for managing disturbance. This study demonstrates the importance of considering human disturbance across different parts of the annual cycle, particularly where multiple forms of recreation have varying spatiotemporal use patterns that create human–wildlife interactions

    Quantization of the interior Schwarzschild black hole

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    We study a Hamiltonian quantum formalism of a spherically symmetric space-time which can be identified with the interior of a Schwarzschild black hole. The phase space of this model is spanned by two dynamical variables and their conjugate momenta. It is shown that the classical Lagrangian of the model gives rise the interior metric of a Schwarzschild black hole. We also show that the the mass of such a system is a Dirac observable and then by quantization of the model by Wheeler-DeWitt approach and constructing suitable wave packets we get the mass spectrum of the black hole.Comment: 12 pages, 1 figure, revised versio

    A Computational Approach to Analyze the Mechanism of Action of the Kinase Inhibitor Bafetinib

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    Prediction of drug action in human cells is a major challenge in biomedical research. Additionally, there is strong interest in finding new applications for approved drugs and identifying potential side effects. We present a computational strategy to predict mechanisms, risks and potential new domains of drug treatment on the basis of target profiles acquired through chemical proteomics. Functional protein-protein interaction networks that share one biological function are constructed and their crosstalk with the drug is scored regarding function disruption. We apply this procedure to the target profile of the second-generation BCR-ABL inhibitor bafetinib which is in development for the treatment of imatinib-resistant chronic myeloid leukemia. Beside the well known effect on apoptosis, we propose potential treatment of lung cancer and IGF1R expressing blast crisis

    Rationalising the role of Keratin 9 as a biomarker for Alzheimer’s disease

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    Keratin 9 was recently identified as an important component of a biomarker panel which demonstrated a high diagnostic accuracy (87%) for Alzheimer’s disease (AD). Understanding how a protein which is predominantly expressed in palmoplantar epidermis is implicated in AD may shed new light on the mechanisms underlying the disease. Here we use immunoassays to examine blood plasma expression patterns of Keratin 9 and its relationship to other AD-associated proteins. We correlate this with the use of an in silico analysis tool VisANT to elucidate possible pathways through which the involvement of Keratin 9 may take place. We identify possible links with Dickkopf-1, a negative regulator of the wnt pathway, and propose that the abnormal expression of Keratin 9 in AD blood and cerebrospinal fluid may be a result of blood brain barrier dysregulation and disruption of the ubiquitin proteasome system. Our findings suggest that dysregulated Keratin 9 expression is a consequence of AD pathology but, as it interacts with a broad range of proteins, it may have other, as yet uncharacterized, downstream effects which could contribute to AD onset and progression

    The disruption of proteostasis in neurodegenerative diseases

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    Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio
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