279 research outputs found

    Joint development of mixed-use transit stations

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    Thesis (M.C.P.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, 2003.Includes bibliographical references (p. [143]-[147]).If rail transit systems are to become a viable means of transportation throughout American cities, urban land use patterns must support the development and use of transit. Transit-oriented development, in which mixed land uses are clustered around transit stations in dense concentrations, offers a means of encouraging transit use and decreasing reliance on automobiles in urban settings. Transit agencies have the opportunity to contribute to this development pattern by incorporating mixed-use transit facilities into their rail systems. These facilities, typically developed through public-private partnerships, incorporate other uses into sites with transit stations. They increase activity around the station and attract additional development to the area. Unfortunately, many transit agencies have little experience with developing mixed use facilities and are reluctant to undertake such projects. The agencies are intimidated by the additional design, financial, and administrative requirements of the development process. The goal of this thesis is to generate a set of principles that provides transit agencies with a foundation of knowledge for approaching mixed-use and joint development projects. The proposed principles strive to maximize the benefits generated by the facilities and increase the likelihood of such development activity occurring successfully. Three aspects of the development process are chosen for attention: site selection, basic elements of facility design, and implementation. The thesis begins with a review of design and development theory and past development strategies to identify the key issues relevant to these types of projects. A set of principles targeting the three aspects of the development process is proposed, based on the issues identified in the research. The principles are then applied to transit agencies and station sites in two cities: San Juan, Puerto Rico and Chicago, Illinois; evaluations and recommendations are made for each city. The application to real world situations allows the principles to be tested and assessed. The thesis concludes with a review of the results for these cities, a critique of the proposed principles, and suggestions for further research on the topic.by Jordan Robert Samuel Karp.M.C.P

    Restorative Justice Approaches To The Informal Resolution Of Student Sexual Misconduct

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    This article reviews controversies about campus Title IX adjudication and the recent implementation of restorative justice (or RJ) responses to campus sexual harm. The RJ approach focuses on who has been harmed, what their needs are, and how the person who harmed them can meet those needs. Instead of engaging in adjudication, RJ aims to get an individual who caused harm to understand the impact of and take responsibility for their actions. Part I defines the RJ approach, describes various practices, and details the preparation necessary for a structured informal resolution process. Part II explains why RJ approaches have been limited to date for Title IX cases and outlines evolving guidance in this realm. Part III reviews legal considerations, including compliance requirements from the Department of Education’s 2020 Final Rule and the implications of the approach for concurrent or subsequent civil or criminal proceedings. Part IV offers three case studies of implementation. Part V summarizes evidence of effectiveness and Part VI concludes. By tracing these essential elements, this article moves beyond the philosophical underpinnings of RJ to offer tools and procedures to consider when adopting RJ for student-on-student sexual misconduct

    Association of molecular senescence markers in late-life depression with clinical characteristics and treatment outcome

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    Importance: Many older adults with depression do not experience remission with antidepressant treatment, and markers of cellular senescence in late-life depression (LLD) are associated with greater severity of depression, greater executive dysfunction, and higher medical illness burden. Since these clinical characteristics are associated with remission in LLD, molecular and cellular senescence abnormalities could be a possible biological mechanism underlying poor treatment response in this population. Objective: To examine whether the senescence-associated secretory phenotype (SASP) index was associated with the likelihood of remission from a depressive episode in older adults. Design, Setting, and Participants: A nonrandomized, open-label clinical trial was conducted between August 2009 and August 2014 in Pittsburgh, Pennsylvania; St Louis, Missouri; and Toronto, Ontario, Canada, with older adults in a current major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) diagnostic criteria. Data from biomarker analyses were reported according to the clinical trial archived plasma samples run in March 2021. Data were analyzed from June to November 2021. Exposure: Venlafaxine extended release (dose ranging from 37.5 mg to 300 mg daily) for up to 12 weeks. Main Outcomes and Measures: The association between a composite biomarker-based index (SASP index) and treatment remission in older adults with major depression was measured using clinical data and blood samples. Results: There were 416 participants with a mean (SD) age of 60.02 (7.13) years; 64% (265 participants) were self-reported female, and the mean (SD) Montgomery-Asberg Depression Rating Scale score was 26.6 (5.7). Higher SASP index scores were independently associated with higher rates of nonremission, with an increase of 1 unit in the SASP index score increasing the odds of nonremission by 19% (adjusted odds ratio, 1.19; 95% CI, 1.05-1.35; P = .006). In contrast, no individual SASP factors were associated with remission in LLD. Conclusions and Relevance: Using clinical data and blood samples from a nonrandomized clinical trial, the results of this study suggest that molecular and cellular senescence, as measured with the SASP index, is associated with worse treatment outcomes in LLD. Combining this index score reflecting interrelated biological processes with other molecular, clinical, and neuroimaging markers may be useful in evaluating antidepressant treatment outcomes. These findings inform a path forward for geroscience-guided interventions targeting senescence to improve remission rates in LLD. Trial Registration: ClinicalTrials.gov Identifier: NCT00892047

    On the geometry of C^3/D_27 and del Pezzo surfaces

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    We clarify some aspects of the geometry of a resolution of the orbifold X = C3/D_27, the noncompact complex manifold underlying the brane quiver standard model recently proposed by Verlinde and Wijnholt. We explicitly realize a map between X and the total space of the canonical bundle over a degree 1 quasi del Pezzo surface, thus defining a desingularization of X. Our analysis relys essentially on the relationship existing between the normalizer group of D_27 and the Hessian group and on the study of the behaviour of the Hesse pencil of plane cubic curves under the quotient.Comment: 23 pages, 5 figures, 2 tables. JHEP style. Added references. Corrected typos. Revised introduction, results unchanged

    Mycorrhizas and biomass crops: opportunities for future sustainable development

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    Central to soil health and plant productivity in natural ecosystems are in situ soil microbial communities, of which mycorrhizal fungi are an integral component, regulating nutrient transfer between plants and the surrounding soil via extensive mycelial networks. Such networks are supported by plant-derived carbon and are likely to be enhanced under coppiced biomass plantations, a forestry practice that has been highlighted recently as a viable means of providing an alternative source of energy to fossil fuels, with potentially favourable consequences for carbon mitigation. Here, we explore ways in which biomass forestry, in conjunction with mycorrhizal fungi, can offer a more holistic approach to addressing several topical environmental issues, including ‘carbon-neutral’ energy, ecologically sustainable land management and CO2 sequestration

    Exploratory genome-wide analyses of cortical inhibition, facilitation, and plasticity in late-life depression

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    Late-life depression (LLD) is a heterogenous mood disorder influenced by genetic factors. Cortical physiological processes such as cortical inhibition, facilitation, and plasticity may be markers of illness that are more strongly associated with genetic factors than the clinical phenotype. Thus, exploring the relationship between genetic factors and these physiological processes may help to characterize the biological mechanisms underlying LLD and improve diagnosis and treatment selection. Transcranial magnetic stimulation (TMS) combined with electromyography was used to measure short interval intracortical inhibition (SICI), cortical silent period (CSP), intracortical facilitation (ICF), and paired associative stimulation (PAS) in 79 participants with LLD. We used exploratory genome-wide association and gene-based analyses to assess for genetic correlations of these TMS measures. MARK4 (which encodes microtubule affinity-regulating kinase 4) and PPP1R37 (which encodes protein phosphatase 1 regulatory subunit 37) showed genome-wide significant association with SICI. EGFLAM (which encodes EGF-like fibronectin type III and laminin G domain) showed genome-wide significant association with CSP. No genes met genome-wide significant association with ICF or PAS. We observed genetic influences on cortical inhibition in older adults with LLD. Replication with larger sample sizes, exploration of clinical phenotype subgroups, and functional analysis of relevant genotypes is warranted to better characterize genetic influences on cortical physiology in LLD. This work is needed to determine whether cortical inhibition may serve as a biomarker to improve diagnostic precision and guide treatment selection in LLD

    Differential colonization with segmented filamentous bacteria and Lactobacillus murinus do not drive divergent development of diet-induced obesity in C57BL/6 mice

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    Alterations in the gut microbiota have been proposed to modify the development and maintenance of obesity and its sequelae. Definition of underlying mechanisms has lagged, although the ability of commensal gut microbes to drive pathways involved in inflammation and metabolism has generated compelling, testable hypotheses. We studied C57BL/6 mice from two vendors that differ in their obesogenic response and in their colonization by specific members of the gut microbiota having well-described roles in regulating gut immune responses. We confirmed the presence of robust differences in weight gain in mice from these different vendors during high fat diet stress. However, neither specific, highly divergent members of the gut microbiota (Lactobacillus murinus, segmented filamentous bacteria) nor the horizontally transmissible gut microbiota were found to be responsible. Constitutive differences in locomotor activity were observed, however. These data underscore the importance of selecting appropriate controls in this widely used model of human obesity

    A wild derived quantitative trait locus on mouse chromosome 2 prevents obesity

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    <p>Abstract</p> <p>Background</p> <p>The genetic architecture of multifactorial traits such as obesity has been poorly understood. Quantitative trait locus (QTL) analysis is widely used to localize loci affecting multifactorial traits on chromosomal regions. However, large confidence intervals and small phenotypic effects of identified QTLs and closely linked loci are impeding the identification of causative genes that underlie the QTLs. Here we developed five subcongenic mouse strains with overlapping and non-overlapping wild-derived genomic regions from an F2 intercross of a previously developed congenic strain, B6.Cg-<it>Pbwg1</it>, and its genetic background strain, C57BL/6J (B6). The subcongenic strains developed were phenotyped on low-fat standard chow and a high-fat diet to fine-map a previously identified obesity QTL. Microarray analysis was performed with Affymetrix GeneChips to search for candidate genes of the QTL.</p> <p>Results</p> <p>The obesity QTL was physically mapped to an 8.8-Mb region of mouse chromosome 2. The wild-derived allele significantly decreased white fat pad weight, body weight and serum levels of glucose and triglyceride. It was also resistant to the high-fat diet. Among 29 genes residing within the 8.8-Mb region, <it>Gpd2, Upp2, Acvr1c, March7 </it>and <it>Rbms1 </it>showed great differential expression in livers and/or gonadal fat pads between B6.Cg-<it>Pbwg1 </it>and B6 mice.</p> <p>Conclusions</p> <p>The wild-derived QTL allele prevented obesity in both mice fed a low-fat standard diet and mice fed a high-fat diet. This finding will pave the way for identification of causative genes for obesity. A further understanding of this unique QTL effect at genetic and molecular levels may lead to the discovery of new biological and pathologic pathways associated with obesity.</p
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