529 research outputs found

    A linear programming-based method for job shop scheduling

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    We present a decomposition heuristic for a large class of job shop scheduling problems. This heuristic utilizes information from the linear programming formulation of the associated optimal timing problem to solve subproblems, can be used for any objective function whose associated optimal timing problem can be expressed as a linear program (LP), and is particularly effective for objectives that include a component that is a function of individual operation completion times. Using the proposed heuristic framework, we address job shop scheduling problems with a variety of objectives where intermediate holding costs need to be explicitly considered. In computational testing, we demonstrate the performance of our proposed solution approach

    In vivo delivery of VEGF RNA and protein to increase osteogenesis and intraosseous angiogenesis

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    Deficient bone vasculature is a key component in pathological conditions ranging from developmental skeletal abnormalities to impaired bone repair. Vascularisation is dependent upon vascular endothelial growth factor (VEGF), which drives both angiogenesis and osteogenesis. The aim of this study was to examine the efcacy of blood vessel and bone formation following transfection with VEGF RNA or delivery of recombinant human VEGF165 protein (rhVEGF165) across in vitro and in vivo model systems. To quantify blood vessels within bone, an innovative approach was developed using high-resolution X-ray computed tomography (XCT) to generate quantifable three-dimensional reconstructions. Application of rhVEGF165 enhanced osteogenesis, as evidenced by increased human osteoblast-like MG-63 cell proliferation in vitro and calvarial bone thickness following in vivo administration. In contrast, transfection with VEGF RNA triggered angiogenic efects by promoting VEGF protein secretion from MG-63VEGF165 cells in vitro, which resulted in signifcantly increased angiogenesis in the chorioallantoic (CAM) assay in ovo. Furthermore, direct transfection of bone with VEGF RNA in vivo increased intraosseous vascular branching. This study demonstrates the importance of continuous supply as opposed to a single high dose of VEGF on angiogenesis and osteogenesis and, illustrates the potential of XCT in delineating in 3D, blood vessel connectivity in bone

    Interaction of the NRF2 and p63 transcription factors promotes keratinocyte proliferation in the epidermis

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    Epigenetic regulation of cell and tissue function requires the coordinated action of transcription factors. However, their combinatorial activities during regeneration remain largely unexplored. Here, we discover an unexpected interaction between the cytoprotective transcription factor NRF2 and p63-a key player in epithelial morphogenesis. Chromatin immunoprecipitation combined with sequencing and reporter assays identifies enhancers and promoters that are simultaneously activated by NRF2 and p63 in human keratinocytes. Modeling of p63 and NRF2 binding to nucleosomal DNA suggests their chromatin-assisted interaction. Pharmacological and genetic activation of NRF2 increases NRF2-p63 binding to enhancers and promotes keratinocyte proliferation, which involves the common NRF2-p63 target cyclin-dependent kinase 12. These results unravel a collaborative function of NRF2 and p63 in the control of epidermal renewal and suggest their combined activation as a strategy to promote repair of human skin and other stratified epithelia

    A quantum McKay correspondence for fractional 2p-branes on LG orbifolds

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    We study fractional 2p-branes and their intersection numbers in non-compact orbifolds as well the continuation of these objects in Kahler moduli space to coherent sheaves in the corresponding smooth non-compact Calabi-Yau manifolds. We show that the restriction of these objects to compact Calabi-Yau hypersurfaces gives the new fractional branes in LG orbifolds constructed by Ashok et. al. in hep-th/0401135. We thus demonstrate the equivalence of the B-type branes corresponding to linear boundary conditions in LG orbifolds, originally constructed in hep-th/9907131, to a subset of those constructed in LG orbifolds using boundary fermions and matrix factorization of the world-sheet superpotential. The relationship between the coherent sheaves corresponding to the fractional two-branes leads to a generalization of the McKay correspondence that we call the quantum McKay correspondence due to a close parallel with the construction of branes on non-supersymmetric orbifolds. We also provide evidence that the boundary states associated to these branes in a conformal field theory description corresponds to a sub-class of the boundary states associated to the permutation branes in the Gepner model associated with the LG orbifold.Comment: LaTeX2e, 1+39 pages, 3 figures (v2) refs added, typos and report no. correcte

    A Room-Temperature Spin-Valve with van der Waals Ferromagnet Fe5GeTe2/Graphene Heterostructure

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    The discovery of van der Waals (vdW) magnets opened a new paradigm for condensed matter physics and spintronic technologies. However, the operations of active spintronic devices with vdW ferromagnets are limited to cryogenic temperatures, inhibiting their broader practical applications. Here, the robust room-temperature operation of lateral spin-valve devices using the vdW itinerant ferromagnet Fe5GeTe2 in heterostructures with graphene is demonstrated. The room-temperature spintronic properties of Fe5GeTe2 are measured at the interface with graphene with a negative spin polarization. Lateral spin-valve and spin-precession measurements provide unique insights by probing the Fe5GeTe2/graphene interface spintronic properties via spin-dynamics measurements, revealing multidirectional spin polarization. Density functional theory calculations in conjunction with Monte Carlo simulations reveal significantly canted Fe magnetic moments in Fe5GeTe2 along with the presence of negative spin polarization at the Fe5GeTe2/graphene interface. These findings open opportunities for vdW interface design and applications of vdW-magnet-based spintronic devices at ambient temperatures

    Climacteric Lowers Plasma Levels of Platelet-Derived Microparticles: A Pilot Study in Pre-versus Postmenopausal Women

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    Background: Climacteric increases the risk of thrombotic events by alteration of plasmatic coagulation. Up to now, less is known about changes in platelet-(PMP) and endothelial cell-derived microparticles (EMP). Methods: In this prospective study, plasma levels of microparticles (MP) were compared in 21 premenopausal and 19 postmenopausal women. Results: No altered numbers of total MP or EMP were measured within the study groups. However, the plasma values of CD61-exposing MP from platelets/megakaryocytes were higher in premenopausal women (5,364 x 10(6)/l, range 4,384-17,167) as compared to postmenopausal women (3,808 x 10(6)/l, range 2,009-8,850; p = 0.020). This differentiation was also significant for the subgroup of premenopausal women without hormonal contraceptives (5,364 x 10(6)/l, range 4,223-15,916; p = 0.047; n = 15). Furthermore, in premenopausal women, higher plasma levels of PMP exposing CD62P were also present as compared to postmenopausal women (288 x 10(6)/l, range 139-462, vs. 121 x 10(6)/l, range 74-284; p = 0.024). This difference was also true for CD63+ PMP levels (281 x 10(6)/l, range 182-551, vs. 137 x 10(6)/l, range 64-432; p = 0.015). Conclusion: Climacteric lowers the level of PMP but has no impact on the number of EMP in women. These data suggest that PMP and EMP do not play a significant role in enhancing the risk of thrombotic events in healthy, postmenopausal women. Copyright (C) 2012 S. Karger AG, Base

    Investigating the Correlation between Performance Scores and Energy Consumption of Mobile Web Apps

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    Context. Developers have access to tools like Google Lighthouse to assess the performance of web apps and to guide the adoption of development best practices. However, when it comes to energy consumption of mobile web apps, these tools seem to be lacking. Goal. This study investigates on the correlation between the performance scores produced by Lighthouse and the energy consumption of mobile web apps. Method. We design and conduct an empirical experiment where 21 real mobile web apps are (i) analyzed via the Lighthouse performance analysis tool and (ii) measured on an Android device running a software-based energy profiler. Then, we statistically assess how energy consumption correlates with the obtained performance scores and carry out an effect size estimation. Results. We discover a statistically significant negative correlation between performance scores and the energy consumption of mobile web apps (with medium to large effect sizes), implying that an increase of the performance score tend to lead to a decrease of energy consumption. Conclusions. We recommend developers to strive to improve the performance level of their mobile web apps, as this can also have a positive impact on their energy consumption on Android devices

    Impairments in hearing and vision impact on mortality in older people: the AGES-Reykjavik Study.

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.to examine the relationships between impairments in hearing and vision and mortality from all-causes and cardiovascular disease (CVD) among older people.population-based cohort study.the study population included 4,926 Icelandic individuals, aged ≥67 years, 43.4% male, who completed vision and hearing examinations between 2002 and 2006 in the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-RS) and were followed prospectively for mortality through 2009.participants were classified as having 'moderate or greater' degree of impairment for vision only (VI), hearing only (HI), and both vision and hearing (dual sensory impairment, DSI). Cox proportional hazard regression, with age as the time scale, was used to calculate hazard ratios (HR) associated with impairment and mortality due to all-causes and specifically CVD after a median follow-up of 5.3 years.the prevalence of HI, VI and DSI were 25.4, 9.2 and 7.0%, respectively. After adjusting for age, significantly (P < 0.01) increased mortality from all causes, and CVD was observed for HI and DSI, especially among men. After further adjustment for established mortality risk factors, people with HI remained at higher risk for CVD mortality [HR: 1.70 (1.27-2.27)], whereas people with DSI remained at higher risk of all-cause mortality [HR: 1.43 (1.11-1.85)] and CVD mortality [HR: 1.78 (1.18-2.69)]. Mortality rates were significantly higher in men with HI and DSI and were elevated, although not significantly, among women with HI.older men with HI or DSI had a greater risk of dying from any cause and particularly cardiovascular causes within a median 5-year follow-up. Women with hearing impairment had a non-significantly elevated risk. Vision impairment alone was not associated with increased mortality.National Institutes of Health, National Institute on Aging (NIA) N01-AG-12100 NIA Z01-AG007380 National Eye Institute (NEI) ZIAEY000401 National Institute on Deafness and Other Communication Disorders (NIDCD) Division of Scientific Programs/IAA Y2-DC-1004-02 Hjartavernd (Icelandic Heart Association) Althingi (Icelandic Parliament

    The International Collaboration for Research methods Development in Oncology (CReDO) workshops: shaping the future of global oncology research

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    Low-income and middle-income countries (LMICs) have a disproportionately high burden of cancer and cancer mortality. The unique barriers to optimum cancer care in these regions necessitate context-specific research. The conduct of research in LMICs has several challenges, not least of which is a paucity of formal training in research methods. Building capacity by training early career researchers is essential to improve research output and cancer outcomes in LMICs. The International Collaboration for Research methods Development in Oncology (CReDO) workshop is an initiative by the Tata Memorial Centre and the National Cancer Grid of India to address gaps in research training and increase capacity in oncology research. Since 2015, there have been five CReDO workshops, which have trained more than 250 oncologists from India and other countries in clinical research methods and protocol development. Participants from all oncology and allied fields were represented at these workshops. Protocols developed included clinical trials, comparative effectiveness studies, health services research, and observational studies, and many of these protocols were particularly relevant to cancer management in LMICs. A follow-up of these participants in 2020 elicited an 88% response rate and showed that 42% of participants had made progress with their CReDO protocols, and 73% had initiated other research protocols and published papers. In this Policy Review, we describe the challenges to research in LMICs, as well as the evolution, structure, and impact of CReDO and other similar workshops on global oncology research
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