1,333 research outputs found
Multicriteria evaluation on accessibility-based transportation equity in road network design problem
This paper investigates the performance of accessibility-based equity measurements in transportation and proposes a multiobjective optimization model to simulate the trade-offs between equity maximization and cost minimization of network construction. The equity is defined as the spatial distribution of accessibilities across zone areas. Six representative indicators were formulated, including GINI coefficient, Theil index, mean log deviation, relative mean deviation, coefficient of variation, and Atkinson index, and incorporated into an equity maximization model to evaluate the performance sensitivity. A bilevel multiobjective optimization model was proposed to obtain the Pareto-optimal solutions for link capacity enhancement in a stochastic road network design problem. A numerical analysis using the Sioux Falls data was implemented. Results verified that the equity indicators are quite sensitive to the pattern of network scenarios in the sense that the level of equity varies according to the amount of overall capacity enhancement as well as the assignment of improved link segments. The suggested multiobjective model that enables representing the Pareto-optimal solutions can provide multiple options in the decision making of road network design.</p
Lutein Protects RGC-5 Cells Against Hypoxia and Oxidative Stress
Retinal ischemia and oxidative stress lead to neuronal death in many ocular pathologies. Recently, we found that lutein, an oxy-carotenoid, protected the inner retina from ischemia/reperfusion injury. However, it is uncertain whether lutein directly protects retinal ganglion cells (RGCs). Here, an in vitro model of hypoxia and oxidative stress was used to further investigate the neuroprotective role of lutein in RGCs. Cobalt chloride (CoCl2) and hydrogen peroxide (H2O2) were added to a transformed RGC cell line, RGC-5, to induce chemical hypoxia and oxidative stress, respectively. Either lutein or vehicle was added to cultured cells. A higher cell count was observed in the lutein-treated cells compared with the vehicle-treated cells. Our data from this in vitro model revealed that lutein might protect RGC-5 cells from damage when exposed to either CoCl2-induced chemical hypoxia or H2O2-induced oxidative stress. These results suggest that lutein may play a role as a neuroprotectant
Community Genetics screening in a pandemic: solutions for pre-test education, informed consent, and specimen collection
A Community Genetics carrier screening program for the Jewish community has operated on-site in high schools in Sydney (Australia) for 25 years. During 2020, in response to the COVID-19 pandemic, government-mandated social-distancing, ‘lock-down’ public health orders, and laboratory supply-chain shortages prevented the usual operation and delivery of the annual testing program. We describe development of three responses to overcome these challenges: (1) pivoting to online education sufficient to ensure informed consent for both genetic and genomic testing; (2) development of contactless telehealth with remote training and supervision for collecting genetic samples using buccal swabs; and (3) a novel patient and specimen identification ‘GeneTrustee’ protocol enabling fully identified clinical-grade specimens to be collected and DNA extracted by a research laboratory while maintaining full participant confidentiality and privacy. These telehealth strategies for education, consent, specimen collection and sample processing enabled uninterrupted delivery and operation of complex genetic testing and screening programs even amid pandemic restrictions. These tools remain available for future operation and can be adapted to other programs
Hierarchies of Susy Splittings and Invisible Photinos as Dark Matter
We explore how to generate hierarchies in the splittings between
superpartners. Some of the consequences are the existence of invisible
components of dark matter, new inflaton candidates, invisible monopoles and a
number of invisible particles that might dominate during various eras, in
particular between BBN and recombination and decay subsequently.Comment: 16 pages. v3: Ref. 27 has been modified. v4: Published versio
Expression of CXCL10 is associated with response to radiotherapy and overall survival in squamous cell carcinoma of the tongue
Five-year survival for patients with oral cancer has been disappointingly stable during the last decades, creating a demand for new biomarkers and treatment targets. Lately, much focus has been set on immunomodulation as a possible treatment or an adjuvant increasing sensitivity to conventional treatments. The objective of this study was to evaluate the prognostic importance of response to radiotherapy in tongue carcinoma patients as well as the expression of the CXC-chemokines in correlation to radiation response in the same group of tumours. Thirty-eight patients with tongue carcinoma that had received radiotherapy followed by surgery were included. The prognostic impact of pathological response to radiotherapy, N-status, T-stage, age and gender was evaluated using Cox's regression models, Kaplan-Meier survival curves and chi-square test. The expression of 23 CXC-chemokine ligands and their receptors were evaluated in all patients using microarray and qPCR and correlated with response to treatment using logistic regression. Pathological response to radiotherapy was independently associated to overall survival with a 2-year survival probability of 81 % for patients showing a complete pathological response, while patients with a non-complete response only had a probability of 42 % to survive for 2 years (p = 0.016). The expression of one CXC-chemokine, CXCL10, was significantly associated with response to radiotherapy and the group of patients with the highest CXCL10 expression responded, especially poorly (p = 0.01). CXCL10 is a potential marker for response to radiotherapy and overall survival in patients with squamous cell carcinoma of the tongue
Association of chronic insomnia symptoms and recurrent extreme sleep duration over 10 years with well-being in older adults: a cohort study
Objectives: The extent to which aspects of sleep affect well-being in the long-term remains unclear. This longitudinal study examines the association between chronic insomnia symptoms, recurrent sleep duration and well-being at older ages. Setting: A prospective cohort of UK civil servants (the Whitehall II study). Participants: 4491 women and men (25.2% women) with sleep measured 3 times over 10 years and wellbeing once at age 55-79 years. Insomnia symptoms and sleep duration were assessed through self-reports in 1997-1999, 2003-2004 and 2007-2009. Primary outcome measures: Indicators of wellbeing, measured in 2007-2009, were the Control, Autonomy, Self-realisation and Pleasure measure (CASP-19) of overall well-being (range 0-57) and the physical and mental well-being component scores (range 0-100) of the Short Form Health Survey (SF-36). Results: In maximally adjusted analyses, chronic insomnia symptoms were associated with poorer overall well-being (difference between insomnia at 3 assessments vs none -7.0 (SE=0.4) p9 h reported at 2 or 3 assessments vs none -3.5 (SE=0.9), p<0.001) were associated with poorer physical well-being. Conclusions: We conclude that in older people, chronic insomnia symptoms are negatively associated with all aspects of well-being, whereas recurrent long and short sleep is only associated with reduced physical well-being
Influence of palaeoweathering on trace metal concentrations and environmental proxies in black shales
The mineralogical and chemical compositions of Lower Carboniferous (Tournaisian) marine black shale from the Kowala quarry, the Holy Cross Mountains, Poland, were investigated. This study focuses on disturbances in palaeoenvironmental proxies caused by palaeoweathering, which progressively changed the major and trace element abundances. Palaeomagnetic investigations reveal that the Devonian – Carboniferous succession was weathered during the Permian-Triassic by the infiltration of oxidizing fluids related to karstification following post-Variscan exhumation. The weathering process led to vermiculitization of chlorite, partial dissolution of calcite and replacement of pyrite by hematite and goethite. Moreover, the concentrations of some trace metals, including Co, Cu, Pb, Mo, Ni, As and U, significantly decreased. Consequently, some elemental abundance ratios that are used as environmental proxies, including U/Th, Ni/Co and V/Cr, were altered. Elements that are bound to iron sulphides (e.g., Mo) appear to be especially prone to mobilization by even a lightly weathered black shale. The documented weathering, including changes in elemental concentrations, can potentially create misinterpretations of the original palaeoenvironmental conditions. In addition, the palaeoweathering of the studied samples appears to have substantially changed the carbon, oxygen, nitrogen and molybdenum stable isotope values. The nitrogen and molybdenum stable isotope ratios, in particular, appear to be most sensitive to the effects of weathering and therefore are good indicators of (palaeo)weathering processes. The major cause of these changes is the decay of organic matter and pyrite. For the organic carbon stable isotopes ratios, the main factor that controlls this process appears to be the preferential degradation of labile organic matter. A combination of the total organic carbon (TOC), total sulphur (TS) content, Mo concentration and stable isotope compositions seems to be the most useful for identify (palaeo)weathering. Our results suggest that reductions in TS and Mo in tandem with diminished Mo stable isotope values in the absence of obvious changes to the TOC content provide the most compelling evidence of (palaeo)weathering
Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders
Personality is influenced by genetic and environmental factors1
and associated with mental health. However, the underlying
genetic determinants are largely unknown. We identified six
genetic loci, including five novel loci2,3, significantly associated
with personality traits in a meta-analysis of genome-wide
association studies (N = 123,132–260,861). Of these genomewide
significant loci, extraversion was associated with variants
in WSCD2 and near PCDH15, and neuroticism with variants
on chromosome 8p23.1 and in L3MBTL2. We performed a
principal component analysis to extract major dimensions
underlying genetic variations among five personality traits
and six psychiatric disorders (N = 5,422–18,759). The first
genetic dimension separated personality traits and psychiatric
disorders, except that neuroticism and openness to experience
were clustered with the disorders. High genetic correlations
were found between extraversion and attention-deficit–
hyperactivity disorder (ADHD) and between openness and
schizophrenia and bipolar disorder. The second genetic
dimension was closely aligned with extraversion–introversion
and grouped neuroticism with internalizing psychopathology
(e.g., depression or anxiety)
Improvement of mammographic mass characterization using spiculation measures and morphological features
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135119/1/mp1548.pd
Interleukin 6 increases production of cytokines by colonic innate lymphoid cells in mice and patients with chronic intestinal inflammation
Background & Aims: Innate lymphoid cells (ILCs) are a heterogeneous group of mucosal inflammatory cells that participate in chronic intestinal inflammation. We investigated the role of interleukin 6 (IL6) in inducing activation of ILCs in mice and in human beings with chronic intestinal inflammation.
Methods:
ILCs were isolated from colons of Tbx21-/- × Rag2-/- mice (TRUC), which develop colitis; patients with inflammatory bowel disease (IBD); and patients without colon inflammation (controls). ILCs were characterized by flow cytometry; cytokine production was measured by enzyme-linked immunosorbent assay and cytokine bead arrays. Mice were given intraperitoneal injections of depleting (CD4, CD90), neutralizing (IL6), or control antibodies. Isolated colon tissues were analyzed by histology, explant organ culture, and cell culture. Bacterial DNA was extracted from mouse fecal samples to assess the intestinal microbiota.
Results:
IL17A- and IL22-producing, natural cytotoxicity receptor-negative, ILC3 were the major subset of ILCs detected in colons of TRUC mice. Combinations of IL23 and IL1α induced production of cytokines by these cells, which increased further after administration of IL6. Antibodies against IL6 reduced colitis in TRUC mice without significantly affecting the structure of their intestinal microbiota. Addition of IL6 increased production of IL17A, IL22, and interferon-γ by human intestinal CD3-negative, IL7-receptor-positive cells, in a dose-dependent manner.
Conclusions:
IL6 contributes to activation of colonic natural cytotoxicity receptor-negative, CD4-negative, ILC3s in mice with chronic intestinal inflammation (TRUC mice) by increasing IL23- and IL1α-induced production of IL17A and IL22. This pathway might be targeted to treat patients with IBD because IL6, which is highly produced in colonic tissue by some IBD patients, also increased the production of IL17A, IL22, and interferon-γ by cultured human colon CD3-negative, IL7-receptor-positive cells
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