888 research outputs found
Odd-primary homotopy exponents of compact simple Lie groups
We note that a recent result of the second author yields upper bounds for
odd-primary homotopy exponents of compact simple Lie groups which are often
quite close to the lower bounds obtained from v_1-periodic homotopy theory.Comment: This is the version published by Geometry & Topology Monographs on 22
February 200
Editorial Special Issue on Enhancement Algorithms, Methodologies and Technology for Spectral Sensing
The paper is an editorial issue on enhancement algorithms, methodologies and technology for spectral sensing and serves as a valuable and useful reference for researchers and technologists interested in the evolving state-of-the-art and/or the emerging science and technology base associated with spectral-based sensing and monitoring problem. This issue is particularly relevant to those seeking new and improved solutions for detecting chemical, biological, radiological and explosive threats on the land, sea, and in the air
The Southern Hospitals Report
When research for this report was first initiated, it was intended to answer a narrow question: is abortion care restricted at historically Protestant hospitals in the U.S. South? Strict limits on access to abortion at Catholic hospitals — and the ways in which this can obstruct and delay even emergency medical care — are already well documented in legal and medical literature and news media. In contrast, restrictions at Protestant hospitals have not been extensively studied and are not well understood. Our research sought to fill this gap in knowledge. We focused on the U.S. South because Catholic hospitals are less concentrated in the South than in other regions (especially the Midwest and Pacific Northwest), leaving Protestant hospitals to play a potentially larger role in the delivery of medical care
A High-Throughput Screen for Wnt/β-Catenin Signaling Pathway Modulators in Human iPSC-Derived Neural Progenitors
Wnt/β-catenin signaling has emerged as a central player in pathways implicated in the pathophysiology and treatment of neuropsychiatric disorders. To identify potential novel therapeutics for these disorders, high-throughput screening (HTS) assays reporting on Wnt/β-catenin signaling in disease-relevant contexts are needed. The use of human patient–derived induced pluripotent stem cell (iPSC) models provides ideal disease-relevant context if these stem cell cultures can be adapted for HTS-compatible formats. Here, we describe a sensitive, HTS-compatible Wnt/β-catenin signaling reporter system generated in homogeneous, expandable neural progenitor cells (NPCs) derived from human iPSCs. We validated this system by demonstrating dose-responsive stimulation by several known Wnt/β-catenin signaling pathway modulators, including Wnt3a, a glycogen synthase kinase-3 (GSK3) inhibitor, and the bipolar disorder therapeutic lithium. These responses were robust and reproducible over time across many repeated assays. We then conducted a screen of ~1500 compounds from a library of Food and Drug Administration–approved drugs and known bioactives and confirmed the HTS hits, revealing multiple chemical and biological classes of novel small-molecule probes of Wnt/β-catenin signaling. Generating these type of pathway-selective, cell-based phenotypic assays in human iPSC-derived neural cells will advance the field of human experimental neurobiology toward the goal of identifying and validating targets for neuropsychiatric disorders.National Institute of Mental Health (U.S.) (Grant R01MH091115)Stanley Medical Research Institut
Stellar Collisions and Ultracompact X-ray Binary Formation
(abridged) We report the results of SPH calculations of parabolic collisions
between a subgiant or slightly evolved red-giant star and a neutron star (NS).
Such collisions are likely to form ultracompact X-ray binaries (UCXBs) observed
today in old globular clusters. In particular, we compute collisions of a 1.4
Msun NS with realistically modelled parent stars of initial masses 0.8 and 0.9
Msun, each at three different evolutionary stages (corresponding to three
different radii R). The distance of closest approach for the initial orbit
varies from 0.04 R (nearly head-on) to 1.3 R (grazing). These collisions lead
to the formation of a tight binary, composed of the NS and the subgiant or
red-giant core, embedded in an extremely diffuse common envelope (CE) typically
of mass ~0.1 to 0.3 Msun. Our calculations follow the binary for many hundreds
of orbits, ensuring that the orbital parameters we determine at the end of the
calculations are close to final. Some of the fluid initially in the envelope of
the (sub)giant, from 0.003 to 0.023 Msun in the cases we considered, is left
bound to the NS. The eccentricities of the resulting binaries range from about
0.2 for our most grazing collision to about 0.9 for the nearly head-on cases.
In almost all the cases we consider, gravitational radiation alone will cause
sufficiently fast orbital decay to form a UCXB within a Hubble time, and often
on a much shorter timescale. Our hydrodynamics code implements the recent SPH
equations of motion derived with a variational approach by Springel & Hernquist
and by Monaghan. Numerical noise is reduced by enforcing an analytic constraint
equation that relates the smoothing lengths and densities of SPH particles. We
present tests of these new methods to help demonstrate their improved accuracy.Comment: 41 pages, 17 figures, accepted by Ap
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Discovery of Small-Molecule Enhancers of Reactive Oxygen Species That are Nontoxic or Cause Genotype-Selective Cell Death
Elevation of reactive oxygen species (ROS) levels has been observed in many cancer cells relative to nontransformed cells, and recent reports have suggested that small-molecule enhancers of ROS may selectively kill cancer cells in various in vitro and in vivo models. We used a high-throughput screening approach to identify several hundred small-molecule enhancers of ROS in a human osteosarcoma cell line. A minority of these compounds diminished the viability of cancer cell lines, indicating that ROS elevation by small molecules is insufficient to induce death of cancer cell lines. Three chemical probes (BRD5459, BRD56491, BRD9092) are highlighted that most strongly elevate markers of oxidative stress without causing cell death and may be of use in a variety of cellular settings. For example, combining nontoxic ROS-enhancing probes with nontoxic doses of l-buthionine sulfoximine, an inhibitor of glutathione synthesis previously studied in cancer patients, led to potent cell death in more than 20 cases, suggesting that even nontoxic ROS-enhancing treatments may warrant exploration in combination strategies. Additionally, a few ROS-enhancing compounds that contain sites of electrophilicity, including piperlongumine, show selective toxicity for transformed cells over nontransformed cells in an engineered cell-line model of tumorigenesis. These studies suggest that cancer cell lines are more resilient to chemically induced increases in ROS levels than previously thought and highlight electrophilicity as a property that may be more closely associated with cancer-selective cell death than ROS elevation.Chemistry and Chemical Biolog
In search of animal normativity : a framework for studying social norms in non-human animals
Funding: K. A. and E. W. were supported by the Templeton World Charity Foundation through the Diverse Intelligence initiative. K. A. was supported by SSHRC 435-2022-0749. S. F. B. was supported by NSF 2127375, NSF SES 1919305, and TWCF0471. T. G. was supported by Swiss National Science Foundation PCEFP1_186832. C. H. was supported by European Union's 8th Framework Programme, Horizon 2020 802719. L. M. H. was supported by NIH U42 OD013117-15A. C. K. was supported by TWCF-20647 and the CIFAR Azrieli Global Scholars program. L. V. L. was supported by the Max Planck Society. J. T. was supported by NIH R21 MH129902 and NIH R01 AG071173.Social norms – rules governing which behaviours are deemed appropriate or inappropriate within a given community – are typically taken to be uniquely human. Recently, this position has been challenged by a number of philosophers, cognitive scientists, and ethologists, who have suggested that social norms may also be found in certain non-human animal communities. Such claims have elicited considerable scepticism from norm cognition researchers, who doubt that any non-human animals possess the psychological capacities necessary for normative cognition. However, there is little agreement among these researchers about what these psychological prerequisites are. This makes empirical study of animal social norms difficult, since it is not clear what we are looking for and thus what should count as behavioural evidence for the presence (or absence) of social norms in animals. To break this impasse, we offer an approach that moves beyond contested psychological criteria for social norms. This approach is inspired by the animal culture research program, which has made a similar shift away from heavily psychological definitions of ‘culture’ to become organised around a cluster of more empirically tractable concepts of culture. Here, we propose an analogous set of constructs built around the core notion of a normative regularity, which we define as a socially maintained pattern of behavioural conformity within a community. We suggest methods for studying potential normative regularities in wild and captive primates. We also discuss the broader scientific and philosophical implications of this research program with respect to questions of human uniqueness, animal welfare and conservation.Publisher PDFPeer reviewe
Multidetector cardiac tomography: A useful tool before cardiac resynchronization therapy
Background: Left ventricular lead placement in a suitable coronary vein is a key determiÂnant of responsiveness to cardiac resynchronization therapy (CRT). Multidetector cardiac tomography (MDCT) is a non-invasive alternative to depict cardiac venous anatomy although coronary sinus (CS) retrograde venography (RV) is the gold standard. The aim of this study was to evaluate the accuracy of MDCT to determine the presence of CS tributaries before CRT.
Methods: A retrospective analysis of 41 consecutive patients eligible to CRT was performed. MDCT was assessed in all patients before CRT and RV was achieved in 39 patients. Both methods evaluated the presence of the inferior interventricular vein (IIV), posterior vein (PV) and lateral main vein (LMV). CS ostium diameter and distance between the CS ostium and right atrium (RA) lateral wall were also measured.
Results: The IIV was identified in 100% of MDCT and in 43.6% of RV. In comparison to RV, the MDCT’s sensitivity to identify PV and LMV was 100% for both, kappa coefficient of 0.792 (CI 95% 0.46–0.93) and 0.69 (CI 95% 0.46–0.91), respectively. There was no significant difference between ischemic and non-ischemic patients regarding the presence of PV or LMV. Median CS antero-posterior diameter was 10.3 mm (IQR 7.5–13) and supero-inferior was 14.1 mm (IQR 11.5–17) (p < 0.01). A positive correlation (p < 0.001) between echocardiographic RA area and the distance from CS ostium to the RA lateral wall in the MDCT was observed.
Conclusions: MDCT is as accurate as RV to depict CS and its tributaries (IIV, PV, LMV), and it could be useful as a non-invasive technique before CRT
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