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

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

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

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

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

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

Depolymerisation of F-actin to G-actin and its repolymerisation in the presence of analogs of adenosine triphosphate

A number of ATP analogs were tested for their ability to depolymerize F-actin and interact with it. It was found that those analogues which are hydrolysable are incorporated into the F-actin polymer whereas the non-hydrolysable ones are displaced from the nucleotide binding site during the polymerization proces

Complement inhibitory stent coating reduces inflammation and neointima formation in New Zealand white rabbits

Purpose: The purpose of this study was to investigate the role of inflammation during stent placement and the value of complement inhibition by stent coating with C1/C3 esterase inhibitor. Inflammation has been described as a major component of restenosis occurring after stent implantation. Methods: Animals were randomly assigned to one of 5 treatment groups and sacrificed after 4 days, and 6 weeks respectively. After 4 days uncoated bare metal control stents (C) (n=8) were compared with polyvinylpyrrolidone coated stents (P) (n=7), and after 6 weeks C stents (n=7) were compared with P stents (n=7) and P C1/C3 esterase inhibitor coated stents (PI) (n=7). AU morphometric measurements were performed on Elastica-van-Gieson stained segments, and the inflammation index (adapted from Kornowski et al.) was assessed using hematoxylin-eosin staining. Results: No acute or subacute thrombosis was observed. After 6 weeks neointima formation was 1.8±0.6 mm2 (bare stent) and 2.6±1.3 mm2 (P) in the control groups. In the treatment group (PI) neointima reduction was detectable (1.5±0.6 mm2). Inflammation was increased by P coating. In the PI stents the inflammation was significantly reduced compared to the P stents. Inflammation was noted 4 days after stent implantation with granulocytes whereas mononuclear infiltrates (lymphocytes, plasma cells) were predominant after 6 weeks. Conclusions: Inflammation is a key component of restenosis following stent administration. Inflammation can be reduced by C1/C3 esterase inhibitor coated stents. Because the hydrogel coating itself induced inflammation, this coating seems not to be the ideal for intravascular use. © Verlag PERFUSION GmbH