860 research outputs found
Work functions of functionalized singled-walled carbon nanotubes
Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2006.Includes bibliographical references (leaves 39-40).Introduction: Carbon nanotube (CNT) structures were discovered by Sumio Iijima in 1991 at NEC laboratories in Japan. Since their discovery, scientists and engineers have been fascinated by their electrical and mechanical properties. Their unique characteristics, in addition to their nanoscale size, have generated much excitement about the possible applications of this novel. material.by Janet Ryu.S.B
A Map of the Inorganic Ternary Metal Nitrides
Exploratory synthesis in novel chemical spaces is the essence of solid-state
chemistry. However, uncharted chemical spaces can be difficult to navigate,
especially when materials synthesis is challenging. Nitrides represent one such
space, where stringent synthesis constraints have limited the exploration of
this important class of functional materials. Here, we employ a suite of
computational materials discovery and informatics tools to construct a large
stability map of the inorganic ternary metal nitrides. Our map clusters the
ternary nitrides into chemical families with distinct stability and
metastability, and highlights hundreds of promising new ternary nitride spaces
for experimental investigation--from which we experimentally realized 7 new Zn-
and Mg-based ternary nitrides. By extracting the mixed metallicity, ionicity,
and covalency of solid-state bonding from the DFT-computed electron density, we
reveal the complex interplay between chemistry, composition, and electronic
structure in governing large-scale stability trends in ternary nitride
materials
Lovastatin enhances adenovirus-mediated TRAIL induced apoptosis by depleting cholesterol of lipid rafts and affecting CAR and death receptor expression of prostate cancer cells
Oncolytic adenovirus and apoptosis inducer TRAIL are promising cancer therapies. Their antitumor efficacy, when used as single agents, is limited. Oncolytic adenoviruses have low infection activity, and cancer cells develop resistance to TRAIL-induced apoptosis. Here, we explored combining prostate-restricted replication competent adenovirus-mediated TRAIL (PRRA-TRAIL) with lovastatin, a commonly used cholesterol-lowering drug, as a potential therapy for advanced prostate cancer (PCa). Lovastatin significantly enhanced the efficacy of PRRA-TRAIL by promoting the in vivo tumor suppression, and the in vitro cell killing and apoptosis induction, via integration of multiple molecular mechanisms. Lovastatin enhanced PRRA replication and virus-delivered transgene expression by increasing the expression levels of CAR and integrins, which are critical for adenovirus 5 binding and internalization. Lovastatin enhanced TRAIL-induced apoptosis by increasing death receptor DR4 expression. These multiple effects of lovastatin on CAR, integrins and DR4 expression were closely associated with cholesterol-depletion in lipid rafts. These studies, for the first time, show correlations between cholesterol/lipid rafts, oncolytic adenovirus infection efficiency and the antitumor efficacy of TRAIL at the cellular level. This work enhances our understanding of the molecular mechanisms that support use of lovastatin, in combination with PRRA-TRAIL, as a candidate strategy to treat human refractory prostate cancer in the future
Cultural orientation of self-bias in perceptual matching
This work was supported by grants from the Economic and Social Research Council (ES/K013424/1), the National Natural Science Foundation of China (31371017), and the Research Grants Council of Hong Kong (HKU758412H)Peer reviewedPublisher PD
Food and Nutrition Extension Programs: Next Generation Impact Evaluation
Grassroots stakeholder input results in relevant and timely Extension programs, but presents a challenge for performance measurement using common indicators. A balanced approach to program evaluation and reporting that is adequately valid and reliable while honoring the Extension culture of service is most likely to be successful. This article reviews recent advances in evaluation methodology of food and nutrition programs. It further describes how this evidence base informs the current set of national Extension program outcomes and indicators. Evaluation work is an essential step in documenting the public value of Extension programs
Timing Specific Requirement of microRNA Function is Essential for Embryonic and Postnatal Hippocampal Development
The adult hippocampus consists of the dentate gyrus (DG) and the CA1, CA2 and CA3 regions and is essential for learning and memory functions. During embryonic development, hippocampal neurons are derived from hippocampal neuroepithelial cells and dentate granular progenitors. The molecular mechanisms that control hippocampal progenitor proliferation and differentiation are not well understood. Here we show that noncoding microRNAs (miRNAs) are essential for early hippocampal development in mice. Conditionally ablating the RNAase III enzyme Dicer at different embryonic time points utilizing three Cre mouse lines causes abnormal hippocampal morphology and affects the number of hippocampal progenitors due to altered proliferation and increased apoptosis. Lack of miRNAs at earlier stages causes early differentiation of hippocampal neurons, in particular in the CA1 and DG regions. Lack of miRNAs at a later stage specifically affects neuronal production in the CA3 region. Our results reveal a timing requirement of miRNAs for the formation of specific hippocampal regions, with the CA1 and DG developmentally hindered by an early loss of miRNAs and the CA3 region to a late loss of miRNAs. Collectively, our studies indicate the importance of the Dicer-mediated miRNA pathway in hippocampal development and functions
A survivin gene signature predicts aggressive tumor behavior
Gene signatures that predict aggressive tumor behavior at the earliest stages of disease, ideally before overt tissue abnormalities, are urgently needed. To search for such genes, we generated a transgenic model of survivin, an essential regulator of cell division and apoptosis overexpressed in cancer. Transgenic expression of survivin in the urinary bladder did not cause histologic abnormalities of the urothelium. However, microarray analysis revealed that survivin-expressing bladders exhibited profound changes in gene expression profile affecting extracellular matrix and inflammatory genes. Following exposure to a bladder carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (OH-BBN), survivin transgenic animals exhibited accelerated tumor progression, preferential incidence of tumors as compared with premalignant lesions, and dramatically abbreviated survival. Conversely, transgenic expression of a survivin Thr34--\u3eAla dominant-negative mutant did not cause changes in gene expression or accelerated tumor progression after OH-BBN treatment. Therefore, survivin expression induces global transcriptional changes in the tissue microenvironment that may promote tumorigenesis. Detection of survivin or its associated gene signature may provide an early biomarker of aggressive tumor behavior before the appearance of tissue abnormalities
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Epigenetic Induction of Cancer-Testis Antigens and Endogenous Retroviruses at Single-Cell Level Enhances Immune Recognition and Response in Glioma
Glioblastoma (GBM) is the most common malignant primary brain tumor and remains incurable. Previous work has shown that systemic administration of Decitabine (DAC) induces sufficient expression of cancer-testis antigens (CTA) in GBM for targeting by adoptive T-cell therapy in vivo. However, the mechanisms by which DAC enhances immunogenicity in GBM remain to be elucidated. Using New York esophageal squamous cell carcinoma 1 (NY-ESO-1) as a representative inducible CTA, we demonstrate in patient tissue, immortalized glioma cells, and primary patient-derived gliomaspheres that basal CTA expression is restricted by promoter hypermethylation in gliomas. DAC treatment of glioma cells specifically inhibits DNA methylation silencing to render NY-ESO-1 and other CTA into inducible tumor antigens at single-cell resolution. Functionally, NY-ESO-1 T-cell receptor-engineered effector cell targeting of DAC-induced antigen in primary glioma cells promotes specific and polyfunctional T-cell cytokine profiles. In addition to induction of CTA, DAC concomitantly reactivates tumor-intrinsic human endogenous retroviruses, interferon response signatures, and MHC-I. Overall, we demonstrate that DAC induces targetable tumor antigen and enhances T-cell functionality against GBM, ultimately contributing to the improvement of targeted immune therapies in glioma.SignificanceThis study dissects the tumor-intrinsic epigenetic and transcriptional mechanisms underlying enhanced T-cell functionality targeting decitabine-induced cancer-testis antigens in glioma. Our findings demonstrate concomitant induction of tumor antigens, reactivation of human endogenous retroviruses, and stimulation of interferon signaling as a mechanistic rationale to epigenetically prime human gliomas to immunotherapeutic targeting
Effects of an internal medicine floor interdisciplinary team on hospital and clinical outcomes of seniors with acute medical illness
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100310/1/ggi12035.pd
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