1,157 research outputs found

    Minimum-weight triangulation is NP-hard

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    A triangulation of a planar point set S is a maximal plane straight-line graph with vertex set S. In the minimum-weight triangulation (MWT) problem, we are looking for a triangulation of a given point set that minimizes the sum of the edge lengths. We prove that the decision version of this problem is NP-hard. We use a reduction from PLANAR-1-IN-3-SAT. The correct working of the gadgets is established with computer assistance, using dynamic programming on polygonal faces, as well as the beta-skeleton heuristic to certify that certain edges belong to the minimum-weight triangulation.Comment: 45 pages (including a technical appendix of 13 pages), 28 figures. This revision contains a few improvements in the expositio

    Differential Proteoglycan Expression in Atherosclerosis Alters Platelet Adhesion and Activation

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    \ua9 2024 by the authors.Proteoglycans are differentially expressed in different atherosclerotic plaque phenotypes, with biglycan and decorin characteristic of ruptured plaques and versican and hyaluronan more prominent in eroded plaques. Following plaque disruption, the exposure of extracellular matrix (ECM) proteins triggers platelet adhesion and thrombus formation. In this study, the impact of differential plaque composition on platelet function and thrombus formation was investigated. Platelet adhesion, activation and thrombus formation under different shear stress conditions were assessed in response to individual proteoglycans and composites representing different plaque phenotypes. The results demonstrated that all the proteoglycans tested mediated platelet adhesion but not platelet activation, and the extent of adhesion observed was significantly lower than that observed with type I and type III collagens. Thrombus formation upon the rupture and erosion ECM composites was significantly reduced (p < 0.05) compared to relevant collagen alone, indicating that proteoglycans negatively regulate platelet collagen responses. This was supported by results demonstrating that the addition of soluble biglycan or decorin to whole blood markedly reduced thrombus formation on type I collagen (p < 0.05). Interestingly, thrombus formation upon the erosion composite displayed aspirin sensitivity, whereas the rupture composite was intensive to aspirin, having implications for current antiplatelet therapy regimes. In conclusion, differential platelet responses and antiplatelet efficacy are observed on ECM composites phenotypic of plaque rupture and erosion. Proteoglycans inhibit thrombus formation and may offer a novel plaque-specific approach to limit arterial thrombosis

    Diagnosis and management of monkeypox in primary care.

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    The monkeypox virus outbreak continues to evolve worldwide. While most people recover without treatment, primary care clinicians may be the first point of contact for those affected. Prompt assessment, diagnosis, isolation, treatment and prophylaxis will reduce the risk of community transmission. The current public health advice is to test suspected cases and monitor close contacts. If individuals test positive for the monkeypox virus, self-isolation at home is recommended for most people with mild symptoms. If patients report severe symptoms, referral and admission to hospital will be needed, where further interventions such as antivirals may be administered. The infection can spread through close contact; therefore, healthcare professionals must take precautions, such as using appropriate personal protective equipment for possible or probable cases

    Sapropterin Treatment Prevents Congenital Heart Defects Induced by Pregestational Diabetes Mellitus in Mice.

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    Background Tetrahydrobiopterin is a cofactor of endothelial NO synthase ( eNOS ), which is critical to embryonic heart development. We aimed to study the effects of sapropterin (Kuvan), an orally active synthetic form of tetrahydrobiopterin on eNOS uncoupling and congenital heart defects ( CHD s) induced by pregestational diabetes mellitus in mice. Methods and Results Adult female mice were induced to pregestational diabetes mellitus by streptozotocin and bred with normal male mice to produce offspring. Pregnant mice were treated with sapropterin or vehicle during gestation. CHD s were identified by histological analysis. Cell proliferation, eNOS dimerization, and reactive oxygen species production were assessed in the fetal heart. Pregestational diabetes mellitus results in a spectrum of CHD s in their offspring. Oral treatment with sapropterin in the diabetic dams significantly decreased the incidence of CHD s from 59% to 27%, and major abnormalities, such as atrioventricular septal defect and double-outlet right ventricle, were absent in the sapropterin-treated group. Lineage tracing reveals that pregestational diabetes mellitus results in decreased commitment of second heart field progenitors to the outflow tract, endocardial cushions, and ventricular myocardium of the fetal heart. Notably, decreased cell proliferation and cardiac transcription factor expression induced by maternal diabetes mellitus were normalized with sapropterin treatment. Furthermore, sapropterin administration in the diabetic dams increased eNOS dimerization and lowered reactive oxygen species levels in the fetal heart. Conclusions Sapropterin treatment in the diabetic mothers improves eNOS coupling, increases cell proliferation, and prevents the development of CHD s in the offspring. Thus, sapropterin may have therapeutic potential in preventing CHD s in pregestational diabetes mellitus

    Microsecond folding dynamics of the F13W G29A mutant of the B domain of staphylococcal protein A by laser-induced temperature jump

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    The small size (58 residues) and simple structure of the B domain of staphylococcal protein A (BdpA) have led to this domain being a paradigm for theoretical studies of folding. Experimental studies of the folding of BdpA have been limited by the rapidity of its folding kinetics. We report the folding kinetics of a fluorescent mutant of BdpA (G29A F13W), named F13W*, using nanosecond laser-induced temperature jump experiments. Automation of the apparatus has permitted large data sets to be acquired that provide excellent signal-to-noise ratio over a wide range of experimental conditions. By measuring the temperature and denaturant dependence of equilibrium and kinetic data for F13W*, we show that thermodynamic modeling of multidimensional equilibrium and kinetic surfaces is a robust method that allows reliable extrapolation of rate constants to regions of the folding landscape not directly accessible experimentally. The results reveal that F13W* is the fastest-folding protein of its size studied to date, with a maximum folding rate constant at 0 M guanidinium chloride and 45°C of 249,000 (s-1). Assuming the single-exponential kinetics represent barrier-limited folding, these data limit the value for the preexponential factor for folding of this protein to at least ≈2 x 10(6) s(-1)

    Experimental evaluation of 3D printed spiral phase plates for enabling an orbital angular momentum multiplexed radio system

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    This paper evaluates the performance of three-dimensionally (3D) printed spiral phase plates (SPPs) for enabling an orbital angular momentum (OAM) multiplexed radio system. The design and realization of the SPPs by means of additive manufacturing exploiting a high-permittivity material is described. Modes 1 and 2 SPPs are then evaluated at 15 GHz in terms of 3D complex radiation pattern, mode purity and beam collimation by means of a 3D printed dielectric lens. The results with the lens yield a crosstalk of −8 dB for between modes 1 and −1, and −11.4 dB for between modes 2 and −2. We suggest a mode multiplexer architecture that is expected to further reduce the crosstalk for each mode. An additional loss of 4.2 dB is incurred with the SPPs inserted into the communication link, which is undesirable for obtaining reliable LTE-based communications. Thus, we suggest: using lower loss materials, seeking ways to reduce material interface reflections or alternative ways of OAM multiplexing to realize a viable OAM multiplexed radio system

    REDfly 2.0: an integrated database of cis-regulatory modules and transcription factor binding sites in Drosophila

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    The identification and study of the cis-regulatory elements that control gene expression are important areas of biological research, but few resources exist to facilitate large-scale bioinformatics studies of cis-regulation in metazoan species. Drosophila melanogaster, with its well-annotated genome, exceptional resources for comparative genomics and long history of experimental studies of transcriptional regulation, represents the ideal system for regulatory bioinformatics. We have merged two existing Drosophila resources, the REDfly database of cis-regulatory modules and the FlyReg database of transcription factor binding sites (TFBSs), into a single integrated database containing extensive annotation of empirically validated cis-regulatory modules and their constituent binding sites. With the enhanced functionality made possible through this integration of TFBS data into REDfly, together with additional improvements to the REDfly infrastructure, we have constructed a one-stop portal for Drosophila cis-regulatory data that will serve as a powerful resource for both computational and experimental studies of transcriptional regulation. REDfly is freely accessible at http://redfly.ccr.buffalo.edu
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