Dynamics and Gravitational Wave Signature of Collapsar Formation

We perform 3+1 general relativistic simulations of rotating core collapse in the context of the collapsar model for long gamma-ray bursts. We employ a realistic progenitor, rotation based on results of stellar evolution calculations, and a simplified equation of state. Our simulations track self-consistently collapse, bounce, the postbounce phase, black hole formation, and the subsequent early hyperaccretion phase. We extract gravitational waves from the spacetime curvature and identify a unique gravitational wave signature associated with the early phase of collapsar formation

Державна грошова допомога як одна із форм соціального захисту дітей-сиріт та дітей, позбавлених батьківського піклування

В статті аналізуються види державної грошової допомоги, які передбачені чинним законодавством України щодо дітей-сиріт та дітей, позбавлених батьківського піклування, а також осіб з їх числа. Сформульовані пропозиції по удосконаленню законодавства про державну соціальну допомогу, застосуванню нових підходів у забезпеченні такою допомогою зазначених осіб.В статье анализируются виды государственной денежной помощи, предусмотренные действующим законодательством Украины по отношению к детям-сиротам и детям, лишенным родительского попечения, а также лицам из их числа. Сформулированы предложения по усовершенствованию законодательства о государственной социальной помощи, применению новых подходов в обеспечении такой помощью вышеуказанных лиц.The article is devoted to the analysis of types of the state monetary (financial) aid, foreseen by the current Ukrainian legislation for children-orphans and children who lost the parental care, as well as persons with the same status. The elaborated proposals on improvement of the legislation concerning the state social aid, as well as introducing new approaches of its granting to the mentioned persons

Bispecific Tau Antibodies with Additional Binding to C1q or Alpha-Synuclein

BACKGROUND: Alzheimer’s disease (AD) and other tauopathies are neurodegenerative disorders characterized by cellular accumulation of aggregated tau protein. Tau pathology within these disorders is accompanied by chronic neuroinflammation, such as activation of the classical complement pathway by complement initiation factor C1q. Additionally, about half of the AD cases present with inclusions composed of aggregated alpha-synuclein called Lewy bodies. Lewy bodies in disorders such as Parkinson’s disease and Lewy body dementia also frequently occur together with tau pathology. OBJECTIVE: Immunotherapy is currently the most promising treatment strategy for tauopathies. However, the presence of multiple pathological processes within tauopathies makes it desirable to simultaneously target more than one disease pathway. METHODS: Herein, we have developed three bispecific antibodies based on published antibody binding region sequences. One bispecific antibody binds to tau plus alpha-synuclein and two bispecific antibodies bind to tau plus C1q. RESULTS: Affinity of the bispecific antibodies to their targets compared to their monospecific counterparts ranged from nearly identical to one order of magnitude lower. All bispecific antibodies retained binding to aggregated protein in patient-derived brain sections. The bispecific antibodies also retained their ability to inhibit aggregation of recombinant tau, regardless of whether the tau binding sites were in IgG or scFv format. Mono- and bispecific antibodies inhibited cellular seeding induced by AD-derived pathological tau with similar efficacy. Finally, both Tau-C1q bispecific antibodies completely inhibited the classical complement pathway. CONCLUSIONS: Bispecific antibodies that bind to multiple pathological targets may therefore present a promising approach to treat tauopathies and other neurodegenerative disorders

Flow computations on imprecise terrains

Abstract. We study water flow computation on imprecise terrains. We consider two approaches to modeling flow on a terrain: one where water flows across the surface of a polyhedral terrain in the direction of steepest descent, and one where water only flows along the edges of a predefined graph, for example a grid or a triangulation. In both cases each vertex has an imprecise elevation, given by an interval of possible values, while its (x, y)-coordinates are fixed. For the first model, we show that the problem of deciding whether one vertex may be contained in the watershed of another is NP-hard. In contrast, for the second model we give a simple O(n log n) time algorithm to compute the minimal and the maximal watershed of a vertex, or a set of vertices, where n is the number of edges of the graph. On a grid model, we can compute the same in O(n) time. Rose knew almost everything that water can do, there are an awful lot when you think what. Gertrude Stein, The World is Round

Antimicrobial Transformation Products in the Aquatic Environment: Global Occurrence, Ecotoxicological Risks, and Potential of Antibiotic Resistance

The global spread of antimicrobial resistance (AMR) isconcerningfor the health of humans, animals, and the environment in a One Healthperspective. Assessments of AMR and associated environmental hazardsmostly focus on antimicrobial parent compounds, while largely overlookingtheir transformation products (TPs). This review lists antimicrobialTPs identified in surface water environments and examines their potentialfor AMR promotion, ecological risk, as well as human health and environmentalhazards using in silico models. Our review also summarizesthe key transformation compartments of TPs, related pathways for TPsreaching surface waters and methodologies for studying the fate ofTPs. The 56 antimicrobial TPs covered by the review were prioritizedvia scoring and ranking of various risk and hazard parameters. Mostdata on occurrences to date have been reported in Europe, while littleis known about antibiotic TPs in Africa, Central and South America,Asia, and Oceania. Occurrence data on antiviral TPs and other antibacterialTPs are even scarcer. We propose evaluation of structural similaritybetween parent compounds and TPs for TP risk assessment. We predicteda risk of AMR for 13 TPs, especially TPs of tetracyclines and macrolides.We estimated the ecotoxicological effect concentrations of TPs fromthe experimental effect data of the parent chemical for bacteria,algae and water fleas, scaled by potency differences predicted byquantitative structure-activity relationships (QSARs) for baselinetoxicity and a scaling factor for structural similarity. Inclusionof TPs in mixtures with their parent increased the ecological riskquotient over the threshold of one for 7 of the 24 antimicrobialsincluded in this analysis, while only one parent had a risk quotientabove one. Thirteen TPs, from which 6 were macrolide TPs, posed arisk to at least one of the three tested species. There were 12/21TPs identified that are likely to exhibit a similar or higher levelof mutagenicity/carcinogenicity, respectively, than their parent compound,with tetracycline TPs often showing increased mutagenicity. Most TPswith increased carcinogenicity belonged to sulfonamides. Most of theTPs were predicted to be mobile but not bioaccumulative, and 14 werepredicted to be persistent. The six highest-priority TPs originatedfrom the tetracycline antibiotic family and antivirals. This review,and in particular our ranking of antimicrobial TPs of concern, cansupport authorities in planning related intervention strategies andsource mitigation of antimicrobials toward a sustainable future

Domain-wall dynamics in 4C pyrrhotite at low temperature

Monoclinic 4C pyrrhotite (Fe7S8) is ferrimagnetic due to an ordered defect structure with alternating vacancy and vacancy-free sublattices. Its low-temperature magnetic transition near 35 K is characterized by the distinct increase in coercivity and remanent magnetization. The increase of these parameters has been attributed to changes in the domain wall structure. We present static and dynamic magnetization data of a powder sample to study the domain-wall dynamics across the low-temperature transition. The amplitude-dependent ac susceptibility and the ferromagnetic resonance spectroscopy indicate that the hardening of the domain-wall pinning at the transition occurs simultaneously with the decrease in initial saturation remanent magnetization. These two effects are explained by the enhanced inhomogeneity of the bulk material caused by the persistency of the ordered vacancies and by newly formed defects due to localized distortion of Fe(II) sites in the vacancy-free sublattice. The generated localized defects are the link between the domain wall dynamics and the low-temperature transition in 4C pyrrhotit

Coronary Microvascular Dysfunction, Microvascular Angina, and Treatment Strategies

AbstractAngina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular dysfunction (CMD) is present in 50% to 65% of these patients. The optimal treatment of this cohort is undefined. We performed a systematic review to evaluate treatment strategies for objectively-defined CMD in the absence of CAD. We included studies assessing therapy in human subjects with angina and coronary flow reserve or myocardial perfusion reserve <2.5 by positron emission tomography, cardiac magnetic resonance imaging, dilution methods, or intracoronary Doppler in the absence of coronary artery stenosis ≥50% or structural heart disease. Only 8 papers met the strict inclusion criteria. The papers were heterogeneous, using different treatments, endpoints, and definitions of CMD. The small sample sizes severely limit the power of these studies, with an average of 11 patients per analysis. Studies evaluating sildenafil, quinapril, estrogen, and transcutaneous electrical nerve stimulation application demonstrated benefits in their respective endpoints. No benefit was found with L-arginine, doxazosin, pravastatin, and diltiazem. Our systematic review highlights that there is little data to support therapies for CMD. We assess the data meeting rigorous inclusion criteria and review the related but excluded published data. We additionally describe the next steps needed to address this research gap, including a standardized definition of CMD, routine assessment of CMD in studies of chest pain without obstructive CAD, and specific therapy assessment in the population with confirmed CMD

Planar bichromatic minimum spanning trees

AbstractGiven a set S of n red and blue points in the plane, a planar bichromatic minimum spanning tree is the shortest possible spanning tree of S, such that every edge connects a red and a blue point, and no two edges intersect. We show that computing this tree is NP-hard in general. For points in convex position, a cubic-time algorithm can be easily designed using dynamic programming. We adapt such an algorithm for the special case where the number of red points (m) is much smaller than the number of blue points (n), resulting in an O(nm2) time algorithm. For the general case, we present a factor O(n) approximation algorithm that runs in O(nlognloglogn) time. Finally, we show that if the number of points in one color is bounded by a constant, the optimal tree can be computed in polynomial time