151 research outputs found

    Mach-Zehnder-Fano interferometer

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    We introduce a concept of the Mach-Zehnder-Fano interferometer by inserting a cavity exhibiting Fano resonance into a conventional interferometer. By employing the scattering-matrix approach, we demonstrate that the transmission is sensitive to a position of the cavity such that an asymmetric structure exhibits a series of narrow resonances with almost perfect reflection. We discuss how to implement this novel geometry in two-dimensional photonic crystals and use direct numerical simulations to demonstrate novel regimes of the resonant transmission and reflection.Comment: 3 pages, 3 figure

    Evaluating Forecasting Methods

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    Ideally, forecasting methods should be evaluated in the situations for which they will be used. Underlying the evaluation procedure is the need to test methods against reasonable alternatives. Evaluation consists of four steps: testing assumptions, testing data and methods, replicating outputs, and assessing outputs. Most principles for testing forecasting methods are based on commonly accepted methodological procedures, such as to prespecify criteria or to obtain a large sample of forecast errors. However, forecasters often violate such principles, even in academic studies. Some principles might be surprising, such as do not use R-square, do not use Mean Square Error, and do not use the within-sample fit of the model to select the most accurate time-series model. A checklist of 32 principles is provided to help in systematically evaluating forecasting methods

    GW8510 Increases Insulin Expression in Pancreatic Alpha Cells through Activation of p53 Transcriptional Activity

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    Background: Expression of insulin in terminally differentiated non-beta cell types in the pancreas could be important to treating type-1 diabetes. Previous findings led us to hypothesize involvement of kinase inhibition in induction of insulin expression in pancreatic alpha cells. Methodology/Principal Findings: Alpha (αTC1.6) cells and human islets were treated with GW8510 and other small-molecule inhibitors for up to 5 days. Alpha cells were assessed for gene- and protein-expression levels, cell-cycle status, promoter occupancy status by chromatin immunoprecipitation (ChIP), and p53-dependent transcriptional activity. GW8510, a putative CDK2 inhibitor, up-regulated insulin expression in mouse alpha cells and enhanced insulin secretion in dissociated human islets. Gene-expression profiling and gene-set enrichment analysis of GW8510-treated alpha cells suggested up-regulation of the p53 pathway. Accordingly, the compound increased p53 transcriptional activity and expression levels of p53 transcriptional targets. A predicted p53 response element in the promoter region of the mouse Ins2 gene was verified by chromatin immunoprecipitation (ChIP). Further, inhibition of Jun N-terminal kinase (JNK) and p38 kinase activities suppressed insulin induction by GW8510. Conclusions/Significance: The induction of Ins2 by GW8510 occurred through p53 in a JNK- and p38-dependent manner. These results implicate p53 activity in modulation of Ins2 expression levels in pancreatic alpha cells, and point to a potential approach toward using small molecules to generate insulin in an alternative cell type.Chemistry and Chemical BiologyMolecular and Cellular Biolog

    The Inhibitory Effect of Salmon Calcitonin on Tri-Iodothyronine Induction of Early Hypertrophy in Articular Cartilage

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    Salmon calcitonin has chondroprotective effect both in vitro and in vivo, and is therefore being tested as a candidate drug for cartilage degenerative diseases. Recent studies have indicated that different chondrocyte phenotypes may express the calcitonin receptor (CTR) differentially. We tested for the presence of the CTR in chondrocytes from tri-iodothyronin (T3)-induced bovine articular cartilage explants. Moreover, investigated the effects of human and salmon calcitonin on the explants.Early chondrocyte hypertrophy was induced in bovine articular cartilage explants by stimulation over four days with 20 ng/mL T3. The degree of hypertrophy was investigated by molecular markers of hypertrophy (ALP, IHH, COLX and MMP13), by biochemical markers of cartilage turnover (C2M, P2NP and AGNxII) and histology. The expression of the CTR was detected by qPCR and immunohistochemistry. T3-induced explants were treated with salmon or human calcitonin. Calcitonin down-stream signaling was measured by levels of cAMP, and by the molecular markers.Compared with untreated control explants, T3 induction increased expression of the hypertrophic markers (p<0.05), of cartilage turnover (p<0.05), and of CTR (p<0.01). Salmon, but not human, calcitonin induced cAMP release (p<0.001). Salmon calcitonin also inhibited expression of markers of hypertrophy and cartilage turnover (p<0.05).T3 induced early hypertrophy of chondrocytes, which showed an elevated expression of the CTR and was thus a target for salmon calcitonin. Molecular marker levels indicated salmon, but not human, calcitonin protected the cartilage from hypertrophy. These results confirm that salmon calcitonin is able to modulate the CTR and thus have chondroprotective effects

    The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact

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    \ua9 2024 The Authors. Alzheimer\u27s &amp; Dementia published by Wiley Periodicals LLC on behalf of Alzheimer\u27s Association.Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. Highlights: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs

    Clinician and Parent Perspectives on Parent and Family Contextual Factors that Impact Community Mental Health Services for Children with Behavior Problems

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    The present study employed qualitative methods to examine multiple stakeholder perspectives regarding the role of parent and family contextual factors on community child mental health treatment for children with behavior problems. Findings suggest agreement between clinicians and parents on the number, types and importance of parent and family factors in children’s mental health services; however, stakeholders differed in reports of which factors were most salient. Specifically, clinicians endorsed most factors as being equally salient, while parents described a few salient factors, with parental stress and inadequate social support being the most frequently discussed. These qualitative data further elucidate the context of community services and have implications for evidence-based practice implementation and improving community care

    The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

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    Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figuresMajor update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figuresThe preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess

    Searches for electroweak production of charginos, neutralinos, and sleptons decaying to leptons and W, Z, and Higgs bosons in pp collisions at 8 TeV

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