5,406 research outputs found

    The Influence of Interference on the Kondo Effect in a Quantum Dot

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    We study the Kondo effect in a model system of a quantum dot embedded in an Aharanov-Bohm ring connected to two leads. By transforming to the scattering basis of the direct inter-lead tunneling, we are able to describe precisely how the Kondo screening of the dot spin occurs. We calculate the Kondo temperature and zero-temperature conductance and find that both are influenced by the Aharanov-Bohm ring as well as the electron density in the leads. We also calculate the form of an additional potential scattering term that arises at low energies due to the breaking of particle-hole symmetry. Many of our results are supported by numerical analysis using the numerical renormalization group.Comment: 24 pages, 18 figure

    The Ah receptor: adaptive metabolism, ligand diversity, and the xenokine model

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    Author Posting. © American Chemical Society, 2020. This is an open access article published under an ACS AuthorChoice License. The definitive version was published in Chemical Research in Toxicology, 33(4), (2020): 860-879, doi:10.1021/acs.chemrestox.9b00476.The Ah receptor (AHR) has been studied for almost five decades. Yet, we still have many important questions about its role in normal physiology and development. Moreover, we still do not fully understand how this protein mediates the adverse effects of a variety of environmental pollutants, such as the polycyclic aromatic hydrocarbons (PAHs), the chlorinated dibenzo-p-dioxins (“dioxins”), and many polyhalogenated biphenyls. To provide a platform for future research, we provide the historical underpinnings of our current state of knowledge about AHR signal transduction, identify a few areas of needed research, and then develop concepts such as adaptive metabolism, ligand structural diversity, and the importance of proligands in receptor activation. We finish with a discussion of the cognate physiological role of the AHR, our perspective on why this receptor is so highly conserved, and how we might think about its cognate ligands in the future.This review is dedicated in memory of the career of Alan Poland, one of the truly great minds in pharmacology and toxicology. This work was supported by the National Institutes of Health Grants R35-ES028377, T32-ES007015, P30-CA014520, P42-ES007381, and U01-ES1026127, The UW SciMed GRS Program, and The Morgridge Foundation. The authors would like to thank Catherine Stanley of UW Media Solutions for her artwork

    Novel paradigm for immunotherapy of breast cancer by engaging prophylactic immunity against hepatitis B

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    Background Immunotherapy of patients suffering from the human epidermal growth factor receptor 2 overexpressing (HER-2+) breast cancers with the anti-HER-2 antibodies results in increase of the patients’ overall survival. However, no prophylactic vaccine is available against HER-2+ breast cancers. Although, prophylactic vaccine for human hepatitis B virus (HBV) is very effective. Specific aim The specific aim of this work was to design, synthesize, and test bio-molecules which would engage prophylactic immunity against hepatitis B virus towards killing breast cancers cells. Methods and Results By biomolecular engineering, we have created a novel family of biomolecules: antibody (anti-HER-2) × vaccine (HBsAg) engineered constructs (AVEC: anti-HER-2 × HBsAg). These biomolecules were utilized for redirecting, accelerating, and amplifying of the vaccination-induced, prophylactic immunity originally targeted against HBV as therapeutic immunity, newly targeted against HER-2+ breast cancers. Treatment of the HER-2+ breast cancer cells with AVEC: anti-HER-2 × HBsAg in blood of the patients, vaccinated with HBsAg, rapidly increased efficacy of killing of HER-2+ breast cancer cells over that attained with the naked anti-HER-2 antibodies. Conclusion Novel antibody-vaccine engineered constructs (AVEC) facilitate redirecting, accelerating, and amplifying of prophylactic, HBV vaccination-induced immunity as immunotherapy (RAAVIIT) of HER-2+ breast cancer. We currently streamline this novel therapeutic paradigm into clinical trials of breast and other cancers

    Reducing low frequency tonal noise in large ducts using a hybrid reactive-dissipative silencer

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    © 2017 Elsevier Ltd Noise generated by fans or turbines normally consists of a combination of narrow and broadband noise. To lower transmitted noise levels, it is attractive to use a combination of reactive and dissipative elements. However, this approach presents a number of challenges for larger systems. This is because reactive elements are commonly placed around the duct circumference where they are normally only effective up to the frequency at which the first higher order mode cuts on in the duct. For larger systems, this means that reactive elements work only in the low, and often very low, frequency range, whereas dissipative elements, which are distributed across the duct cross-section, generally work well in the medium to high frequency range. This can cause noise problems in the low to medium frequency range in larger systems. This article presents an alternative approach for delivering noise attenuation over the low to medium frequency range that is suitable for application in larger duct systems. This approach takes advantage of those splitter silencer designs commonly used in larger systems to integrate a reactive element into the splitter design. This delivers a hybrid splitter that uses a combination of dissipative and reactive elements so that the reactive element partitions the main airway. This has the advantage of introducing a quasi-planar transverse sound pressure field for each resonator in the low to medium frequency range, including frequencies above the first cut-on. It is demonstrated using predictions and measurements taken for a number of example silencers, that this approach enables reactive elements to work over an extended low to medium frequency range, including at frequencies above the first cut-on mode in the main duct. Accordingly, it is shown that a hybrid dissipative-reactive splitter design is capable of delivering improved levels of attenuation in the crucial low to medium frequency range

    The association between neighborhood economic hardship, the retail food environment, fast food intake, and obesity: findings from the Survey of the Health of Wisconsin

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    Background: Neighborhood-level characteristics such as economic hardship and the retail food environment are assumed to be correlated and to influence consumers' dietary behavior and health status, but few studies have investigated these different relationships comprehensively in a single study. This work aims to investigate the association between neighborhood-level economic hardship, the retail food environment, fast food consumption, and obesity prevalence. Methods: Linking data from the population-based Survey of the Health of Wisconsin (SHOW, n = 1,570, 2008-10) and a commercially available business database, the Wisconsin Retail Food Environment Index (WRFEI) was defined as the mean distance from each participating household to the three closest supermarkets divided by the mean distance to the three closest convenience stores or fast food restaurants. Based on US census data, neighborhood-level economic hardship was defined by the Economic Hardship Index (EHI). Relationships were analyzed using multivariate linear and logistic regression models. Results: SHOW residents living in neighborhoods with the highest economic hardship faced a less favorable retail food environment (WRFEI = 2.53) than residents from neighborhoods with the lowest economic hardship (WRFEI = 1.77; p-trend < 0.01). We found no consistent or significant associations between the WRFEI and obesity and only a weak borderline-significant association between access to fast food restaurants and self-reported fast food consumption (≥2 times/week, OR = 0.59-0.62, p = 0.05-0.09) in urban residents. Participants reporting higher frequency of fast food consumption (≥2 times vs. <2 times per week) were more likely to be obese (OR = 1.35, p = 0.06). Conclusion: This study indicates that neighborhood-level economic hardship is associated with an unfavorable retail food environment. However inconsistent or non-significant relationships between the retail food environment, fast food consumption, and obesity were observed. More research is needed to enhance methodological approaches to assess the retail food environment and to understand the complex relationship between neighborhood characteristics, health behaviors, and health outcomes

    The linearization of the Kodama state

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    We study the question of whether the linearization of the Kodama state around classical deSitter spacetime is normalizable in the inner product of the theory of linearized gravitons on deSitter spacetime. We find the answer is no in the Lorentzian theory. However, in the Euclidean theory the corresponding linearized Kodama state is delta-functional normalizable. We discuss whether this result invalidates the conjecture that the full Kodama state is a good physical state for quantum gravity with positive cosmological constant.Comment: 14 pages, statement on the corresponding Yang-Mills case correcte

    Barcode sequencing and a high-throughput assay for chronological lifespan uncover ageing-associated genes in fission yeast

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    Ageing-related processes are largely conserved, with simple organisms remaining the main platform to discover and dissect new ageing-associated genes. Yeasts provide potent model systems to study cellular ageing owing their amenability to systematic functional assays under controlled conditions. Even with yeast cells, however, ageing assays can be laborious and resource-intensive. Here we present improved experimental and computational methods to study chronological lifespan in Schizosaccharomyces pombe. We decoded the barcodes for 3206 mutants of the latest gene-deletion library, enabling the parallel profiling of ~700 additional mutants compared to previous screens. We then applied a refined method of barcode sequencing (Bar-seq), addressing technical and statistical issues raised by persisting DNA in dead cells and sampling bottlenecks in aged cultures, to screen for mutants showing altered lifespan during stationary phase. This screen identified 341 long-lived mutants and 1246 short-lived mutants which point to many previously unknown ageing-associated genes, including 46 conserved but entirely uncharacterized genes. The ageing-associated genes showed coherent enrichments in processes also associated with human ageing, particularly with respect to ageing in non-proliferative brain cells. We also developed an automated colony-forming unit assay to facilitate medium- to high-throughput chronological-lifespan studies by saving time and resources compared to the traditional assay. Results from the Bar-seq screen showed good agreement with this new assay. This study provides an effective methodological platform and identifies many new ageing-associated genes as a framework for analysing cellular ageing in yeast and beyond

    Molecular self-organization: Predicting the pattern diversity and lowest energy state of competing ordering motifs

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    Self-organized monolayers of highly flexible \Frechet dendrons were deposited on graphite surfaces by solution casting. Scanning tunneling microscopy (STM) reveals an unprecedented variety of patterns with up to seven stable hierarchical ordering motifs serving as a versatile model system. The essential molecular properties determined by molecular mechanics simulations are condensed to a coarse grained interaction site model of various chain configurations. In a Monte Carlo approach with random starting configurations the experimental pattern diversity can be reproduced in all facets of the local and global ordering. Based on an energy analysis of the Monte Carlo and molecular mechanics modeling the thermodynamically most stable pattern is predicted coinciding with the pattern, which dominates in the STM images after several hours or upon moderate heating.Comment: 6 pages, 7 figure

    Examining the Connections within the Startup Ecosystem: A Case Study of St. Louis

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    This paper documents the resurgence of entrepreneurial activity in St. Louis by reporting on the collaboration and local learning within the startup community. This activity is happening both between entrepreneurs and between organizations that provide support, such as mentoring and funding, to entrepreneurs. As these connections deepen, the strength of the entrepreneurial ecosystem grows. Another finding from the research is that activity-based events, where entrepreneurs have the chance to use and practice the skills needed to grow their businesses, are most useful. St. Louis provides a multitude of these activities, such as Startup Weekend, 1 Million Cups, Code Until Dawn, StartLouis, and GlobalHack. Some of these are St. Louis specific, but others have nationwide or global operations, providing important implications for other cities
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