1,941 research outputs found

    The consumer response to photovoltaics: the MIT Sun Day experience

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    This paper reports on the results of the MIT Energy Laboratory Sun Day PV study. This study continued our assessment of likely market response to photovoltaics. The Sun Day exhibit attracted a high proportion of solar inno- vators. The study determined that the key issues relating to PV preference are - economical and ecological soundness - complexity of the system and - secondary benefits. A key result is that this population is much more receptive to PV than were populations previously studied, but we were not able to identify external characteristics associated with that innovativeness.Prepared for the U.S. Dept. of Energy under Contract no. EX-76-A-01-2295, Task order 37

    Rerouting Flows When Links Fail

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    We introduce and investigate reroutable flows, a robust version of network flows in which link failures can be mitigated by rerouting the affected flow. Given a capacitated network, a path flow is reroutable if after failure of an arbitrary arc, we can reroute the interrupted flow from the tail of that arc to the sink, without modifying the flow that is not affected by the failure. Similar types of restoration, which are often termed "local", were previously investigated in the context of network design, such as min-cost capacity planning. In this paper, our interest is in computing maximum flows under this robustness assumption. An important new feature of our model, distinguishing it from existing max robust flow models, is that no flow can get lost in the network. We also study a tightening of reroutable flows, called strictly reroutable flows, making more restrictive assumptions on the capacities available for rerouting. For both variants, we devise a reroutable-flow equivalent of an s-t-cut and show that the corresponding max flow/min cut gap is bounded by 2. It turns out that a strictly reroutable flow of maximum value can be found using a compact LP formulation, whereas the problem of finding a maximum reroutable flow is NP-hard, even when all capacities are in {1, 2}. However, the tightening can be used to get a 2-approximation for reroutable flows. This ratio is tight in general networks, but we show that in the case of unit capacities, every reroutable flow can be transformed into a strictly reroutable flow of same value. While it is NP-hard to compute a maximal integral flow even for unit capacities, we devise a surprisingly simple combinatorial algorithm that finds a half-integral strictly reroutable flow of value 1, or certifies that no such solutions exits. Finally, we also give a hardness result for the case of multiple arc failures

    Human Beta Defensins and Cancer: Contradictions and Common Ground

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    Human beta-defensins (hBDs, −1, 2, 3) are a family of epithelial cell derived antimicrobial peptides (AMPs) that protect mucosal membranes from microbial challenges. In addition to their antimicrobial activities, they possess other functions; e.g., cell activation, proliferation, regulation of cytokine/chemokine production, migration, differentiation, angiogenesis, and wound healing processes. It has also become apparent that defensin levels change with the development of neoplasia. However, inconsistent observations published by various laboratories make it difficult to reach a consensus as to the direction of the dysregulation and role the hBDs may play in various cancers. This is particularly evident in studies focusing on oral squamous cell carcinoma (OSCC). By segregating each hBD by cancer type, interrogating methodologies, and scrutinizing the subject cohorts used in the studies, we have endeavored to identify the “take home message” for each one of the three hBDs. We discovered that (1) consensus-driven findings indicate that hBD-1 and−2 are down- while hBD-3 is up-regulated in OSCC; (2) hBD dysregulation is cancer-type specific; (3) the inhibition/activation effect an hBD has on cancer cell lines is related to the direction of the hBD dysregulation (up or down) in the cancer from which the cell lines derive. Therefore, studies addressing hBD dysregulation in various cancers are not generalizable and comparisons should be avoided. Systematic delineation of the fate and role of the hBDs in a specific cancer type may lead to innovative ways to use defensins as prospective biomarkers for diagnostic/prognostic purposes and/or in novel therapeutic modalities

    Measuring Affinities of Fission Yeast Spindle Pole Body Proteins in Live Cells across the Cell Cycle

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    AbstractCharacterizing protein-protein interactions is essential for understanding molecular mechanisms, although reproducing cellular conditions in vitro is challenging and some proteins are difficult to purify. We developed a method to measure binding to cellular structures using fission yeast cells as reaction vessels. We varied the concentrations of Sid2p and Mob1p (proteins of the septation initiation network) and measured their binding to spindle pole bodies (SPBs), the centrosome equivalent of yeast. From our measurements we infer that Sid2p and Mob1p both exist as monomeric, heterodimeric, and homodimeric species throughout the cell cycle. During interphase these species have widely different affinities for their common receptor Cdc11p on the SPB. The data support a model with a subset of Cdc11p binding the heterodimeric species with a Kd < 0.1 μM when Sid2p binds Mob1p-Cdc11p and Kd in the micromolar range when Mob1p binds Sid2p-Cdc11p. During mitosis an additional species presumed to be the phosphorylated Sid2p−Mob1p heterodimer binds SPBs with a lower affinity. Homodimers of Sid2p or Mob1p bind to the rest of Cdc11p at SPBs with lower affinity: Kds > 10 μM during interphase and somewhat stronger during mitosis. These measurements allowed us to account for the fluctuations in Sid2p binding to SPBs throughout the cell cycle

    Characterization and partial purification of Candida albicans Secretory IL-12 Inhibitory Factor

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    Š 2008 Wang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

    A Detailed Observational Analysis of V1324 Sco, the Most Gamma-Ray Luminous Classical Nova to Date

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    It has recently been discovered that some, if not all, classical novae emit GeV gamma rays during outburst, but the mechanisms involved in the production of the gamma rays are still not well understood. We present here a comprehensive multi-wavelength dataset---from radio to X-rays---for the most gamma-ray luminous classical nova to-date, V1324 Sco. Using this dataset, we show that V1324 Sco is a canonical dusty Fe-II type nova, with a maximum ejecta velocity of 2600 km s−1^{-1} and an ejecta mass of few ×10−5\times 10^{-5} M⊙_{\odot}. There is also evidence for complex shock interactions, including a double-peaked radio light curve which shows high brightness temperatures at early times. To explore why V1324~Sco was so gamma-ray luminous, we present a model of the nova ejecta featuring strong internal shocks, and find that higher gamma-ray luminosities result from higher ejecta velocities and/or mass-loss rates. Comparison of V1324~Sco with other gamma-ray detected novae does not show clear signatures of either, and we conclude that a larger sample of similarly well-observed novae is needed to understand the origin and variation of gamma rays in novae.Comment: 26 pages, 13 figure

    Signal peptide cleavage is essential for surface expression of a regulatory T cell surface protein, leucine rich repeat containing 32 (LRRC32)

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    <p>Abstract</p> <p>Background</p> <p>Elevated numbers of regulatory T cells (T<sub>regs</sub>) have been implicated in certain cancers. Depletion of T<sub>regs </sub>has been shown to increase anti-tumor immunity. T<sub>regs </sub>also play a critical role in the suppression of autoimmune responses. The study of T<sub>regs </sub>has been hampered by a lack of adequate surface markers. Leucine Rich Repeat Containing 32 (LRRC32), also known as Glycoprotein A Repetitions Predominant (GARP), has been postulated as a novel surface marker of activated T<sub>regs</sub>. However, there is limited information regarding the processing of LRRC32 or the regulatory phenotype and functional activity of T<sub>regs </sub>expressing LRRC32.</p> <p>Results</p> <p>Using naturally-occurring freshly isolated T<sub>regs</sub>, we demonstrate that low levels of LRRC32 are present intracellularly prior to activation and that freshly isolated LRRC32<sup>+ </sup>T<sub>regs </sub>are distinct from LRRC32<sup>- </sup>T<sub>regs </sub>with respect to the expression of surface CD62L. Using LRRC32 transfectants of HEK cells, we demonstrate that the N-terminus of LRRC32 is cleaved prior to expression of the protein at the cell surface. Furthermore, we demonstrate using a construct containing a deleted putative signal peptide region that the presence of a signal peptide region is critical to cell surface expression of LRRC32. Finally, mixed lymphocyte assays demonstrate that LRRC32<sup>+ </sup>T<sub>regs </sub>are more potent suppressors than LRRC32<sup>- </sup>T<sub>regs</sub>.</p> <p>Conclusions</p> <p>A cleaved signal peptide site in LRRC32 is necessary for surface localization of native LRRC32 following activation of naturally-occurring freshly-isolated regulatory T cells. LRRC32 expression appears to alter the surface expression of activation markers of T cells such as CD62L. LRRC32 surface expression may be useful as a marker that selects for more potent T<sub>reg </sub>populations. In summary, understanding the processing and expression of LRRC32 may provide insight into the mechanism of action of T<sub>regs </sub>and the refinement of immunotherapeutic strategies aimed at targeting these cells.</p

    Photodynamic Therapy with the Silicon Phthalocyanine Pc 4 Induces Apoptosis in Mycosis Fungoides and Sezary Syndrome

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    Our current focus on the effects of Photodynamic Therapy (PDT) using silicon phthalocyanine Pc 4 photosensitizer on malignant T lymphocytes arose due to preclinical observations that Jurkat cells, common surrogate for human T cell lymphoma, were more sensitive to Pc 4-PDT-induced killing than epidermoid carcinoma A431 cells. Mycosis fungoides (MF) as well as Sezary syndrome (SS) are variants of cutaneous T-cell lymphoma (CTCL) in which malignant T-cells invade the epidermis. In this study, we investigated the cytotoxicity of Pc 4-PDT in peripheral blood cells obtained from patients with SS and in skin biopsies of patients with MF. Our data suggest that Pc 4-PDT preferentially induces apoptosis of CD4+CD7− malignant T-lymphocytes in the blood relative to CD11b+ monocytes and nonmalignant T-cells. In vivo Pc 4-PDT of MF skin also photodamages the antiapoptotic protein Bcl-2
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