The Laser Interferometer Gravitational Wave Observatory (LIGO) has been directly detecting gravitational waves from compact binary mergers since 2015. We report on the first use of squeezed vacuum ...states in the direct measurement of gravitational waves with the Advanced LIGO H1 and L1 detectors. This achievement is the culmination of decades of research to implement squeezed states in gravitational-wave detectors. During the ongoing O3 observation run, squeezed states are improving the sensitivity of the LIGO interferometers to signals above 50 Hz by up to 3 dB, thereby increasing the expected detection rate by 40% (H1) and 50% (L1).
Heparan sulfate (HS) proteoglycans bind extracellular proteins that participate in cell signaling, attachment and endocytosis. These interactions depend on the arrangement of sulfated sugars in the ...HS chains generated by well-characterized biosynthetic enzymes; however, the regulation of these enzymes is largely unknown. We conducted genome-wide CRISPR-Cas9 screens with a small-molecule ligand that binds to HS. Screening of A375 melanoma cells uncovered additional genes and pathways impacting HS formation. The top hit was the epigenetic factor KDM2B, a histone demethylase. KDM2B inactivation suppressed multiple HS sulfotransferases and upregulated the sulfatase SULF1. These changes differentially affected the interaction of HS-binding proteins. KDM2B-deficient cells displayed decreased growth rates, which was rescued by SULF1 inactivation. In addition, KDM2B deficiency altered the expression of many extracellular matrix genes. Thus, KDM2B controls proliferation of A375 cells through the regulation of HS structure and serves as a master regulator of the extracellular matrix.
Heparin is the most widely prescribed biopharmaceutical in production globally. Its potent anticoagulant activity and safety makes it the drug of choice for preventing deep vein thrombosis and ...pulmonary embolism. In 2008, adulterated material was introduced into the heparin supply chain, resulting in several hundred deaths and demonstrating the need for alternate sources of heparin. Heparin is a fractionated form of heparan sulfate derived from animal sources, predominantly from connective tissue mast cells in pig mucosa. While the enzymes involved in heparin biosynthesis are identical to those for heparan sulfate, the factors regulating these enzymes are not understood. Examination of the promoter regions of all genes involved in heparin/heparan sulfate assembly uncovered a transcription factor-binding motif for ZNF263, a C2H2 zinc finger protein. CRISPR-mediated targeting and siRNA knockdown of ZNF263 in mammalian cell lines and human primary cells led to dramatically increased expression levels of HS3ST1, a key enzyme involved in imparting anticoagulant activity to heparin, and HS3ST3A1, another glucosaminyl 3-O-sulfotransferase expressed in cells. Enhanced 3-O-sulfation increased binding to antithrombin, which enhanced Factor Xa inhibition, and binding of neuropilin-1. Analysis of transcriptomics data showed distinctively low expression of ZNF263 in mast cells compared with other (non–heparinproducing) immune cells. These findings demonstrate a novel regulatory factor in heparan sulfate modification that could further advance the possibility of bioengineering anticoagulant heparin in cultured cells.
Black hole in a superconducting plasma Bhattacharjee, Chinmoy; Feng, Justin C.; Mahajan, S. M.
Physical review. D,
01/2019, Letnik:
99, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The generalized vortical formalism provides an electrodynamic description for superconducting states-in the generalized vortical formalism, a superconducting state may be defined by the vanishing of ...an appropriate generalized vorticity and characterized by zero generalized helicity for incompressible fluids. In this article, we investigate these states for incompressible plasmas in black hole spacetime geometries using the curved spacetime generalization of the grand generalized vortical formalism. If the magnetic field is axisymmetric and the thermodynamic properties are symmetric about the equatorial plane, the resulting states are characterized by a vanishing skin depth and a complete expulsion of the magnetic field at the equator of the black hole horizon. Moreover, if the thermodynamic properties of the plasma are uniform at the horizon, we find that the magnetic field is completely expelled from the horizon, and the plasma behaves as a perfect superconductor near the horizon. This result is independent of the spin of a black hole, holding even for a (nonrotating) Schwarzschild black hole, and demonstrates that the geometry near black hole horizons can have a significant effect on the electrodynamics of surrounding plasmas.
This large, prospective, community-based study characterized neuropsychological functioning and academic achievement at the time of the first recognized seizure and identified risk factors for ...cognitive deficits.
We compared 282 children (ages 6-14 years, IQ > or =70) with a first recognized seizure to 147 healthy siblings on a battery of well-standardized and widely used neuropsychological and academic achievement tests and examined relationships with demographic and clinical variables.
In this intellectually normal cohort, 27% with just one seizure and up to 40% of those with risk factors exhibited neuropsychological deficits at or near onset. Risk factors associated with neuropsychological deficits included multiple seizures (i.e., second unprovoked seizure; odds ratio OR = 1.96), use of antiepileptic drugs (OR = 2.27), symptomatic/cryptogenic etiology (OR = 2.15), and epileptiform activity on the initial EEG (OR = 1.90); a child with all 4 risks is 3.00 times more likely than healthy siblings to experience neuropsychological deficits by the first clinic visit. Absence epilepsy carried increased odds for neuropsychological impairment (OR = 2.00).
A subgroup of intellectually normal children with seizures showed neuropsychological deficits at onset. Academic achievement was unaffected, suggesting that there is a window early in the disorder for intervention to ameliorate the impact on school performance. Therefore, the risk factors identified here (especially if multiple risks are present) warrant swift referral for neuropsychological evaluation early in the course of the condition.
Size effects in heat conduction, which occur when phonon mean free paths (MFPs) are comparable to characteristic lengths, are being extensively explored in many nanoscale systems for energy ...applications. Knowledge of MFPs is essential to understanding size effects, yet MFPs are largely unknown for most materials. Here, we introduce the first experimental technique which can measure MFP distributions over a wide range of length scales and materials. Using this technique, we measure the MFP distribution of silicon for the first time and obtain good agreement with first-principles calculations.
Summary Background A lack of agreement on definitions and terminology used for nutrition-related concepts and procedures limits the development of clinical nutrition practice and research. Objective ...This initiative aimed to reach a consensus for terminology for core nutritional concepts and procedures. Methods The European Society of Clinical Nutrition and Metabolism (ESPEN) appointed a consensus group of clinical scientists to perform a modified Delphi process that encompassed e-mail communication, face-to-face meetings, in-group ballots and an electronic ESPEN membership Delphi round. Results Five key areas related to clinical nutrition were identified: concepts; procedures; organisation; delivery; and products. One core concept of clinical nutrition is malnutrition/undernutrition, which includes disease-related malnutrition (DRM) with (eq. cachexia) and without inflammation, and malnutrition/undernutrition without disease, e.g. hunger-related malnutrition. Over-nutrition (overweight and obesity) is another core concept. Sarcopenia and frailty were agreed to be separate conditions often associated with malnutrition. Examples of nutritional procedures identified include screening for subjects at nutritional risk followed by a complete nutritional assessment. Hospital and care facility catering are the basic organizational forms for providing nutrition. Oral nutritional supplementation is the preferred way of nutrition therapy but if inadequate then other forms of medical nutrition therapy, i.e. enteral tube feeding and parenteral (intravenous) nutrition, becomes the major way of nutrient delivery. Conclusion An agreement of basic nutritional terminology to be used in clinical practice, research, and the ESPEN guideline developments has been established. This terminology consensus may help to support future global consensus efforts and updates of classification systems such as the International Classification of Disease (ICD). The continuous growth of knowledge in all areas addressed in this statement will provide the foundation for future revisions.
Recent work demonstrates that stochastic fluctuations in molecular populations have consequences for gene regulation. Previous experiments focused on noise sources or noise propagation through gene ...networks by measuring noise magnitudes. However, in theoretical analysis, we showed that noise frequency content is determined by the underlying gene circuits, leading to a mapping between gene circuit structure and the noise frequency range. An intriguing prediction from our previous studies was that negative autoregulation shifts noise to higher frequencies where it is more easily filtered out by gene networks—a property that may contribute to the prevalence of autoregulation motifs (for example, found in the regulation of ∼40% of Escherichia coli genes). Here we measure noise frequency content in growing cultures of E. coli, and verify the link between gene circuit structure and noise spectra by demonstrating the negative autoregulation-mediated spectral shift. We further demonstrate that noise spectral measurements provide mechanistic insights into gene regulation, as perturbations of gene circuit parameters are discernible in the measured noise frequency ranges. These results suggest that noise spectral measurements could facilitate the discovery of novel regulatory relationships.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background There is increasing interest in reducing the duration of mechanical ventilation after pediatric cardiac operations. However, the contemporary use of an early extubation strategy and its ...effect on clinical outcomes is poorly understood. Methods Data from The Society of Thoracic Surgeons Congenital Heart Surgery Database (2010 to 2013) were analyzed to determine the association of early extubation with postoperative length of stay (PLOS). Two operations were analyzed: complete repair of tetralogy of Fallot (TOF) in patients older than 45 days and the Fontan procedure. Centers were stratified into tertiles by frequency of early extubation, defined as less than 6 hours after leaving the operating room. Patients extubated after 48 hours were excluded. Results Among 92 centers, early extubation was performed in 31.5% (478 of 1,519) of children undergoing TOF repair and in 69.8% (1,153 of 1,653) of those undergoing the Fontan procedure. Early extubation after TOF repair was associated with heavier weight at operation ( p < 0.001) and fewer preoperative risk factors ( p = 0.016). After adjustment for covariates, average PLOS after TOF repair was shorter for centers in the highest tertile of early extubation rate than for the lowest tertile centers, which have low early extubation rate ( p = 0.04). No association was found between center early extubation rate and PLOS for Fontan procedures ( p = 0.08). Conclusions Early extubation is common after repair of TOF and the Fontan procedure. A high institutional rate of early extubation after TOF repair is associated with shorter PLOS. Further analysis is needed to understand what effect early extubation might have on other meaningful measures such as resource use.
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