Connectivity percolation in suspensions of hard platelets

We present a study on connectivity percolation in suspensions of hard platelets by means of Monte Carlo simulation. We interpret our results using a contact-volume argument based on an effective single--particle cell model. It is commonly assumed that the percolation threshold of anisotropic objects scales as their inverse aspect ratio. While this rule has been shown to hold for rod-like particles, we find that for hard plate-like particles the percolation threshold is non-monotonic in the aspect ratio. It exhibits a shallow minimum at intermediate aspect ratios and then saturates to a constant value. This effect is caused by the isotropic-nematic transition pre-empting the percolation transition. Hence the common strategy to use highly anisotropic, conductive particles as fillers in composite materials in order to produce conduction at low filler concentration is expected to fail for plate-like fillers such as graphene and graphite nanoplatelets

Trauma and Trichotillomania: A Tenuous Relationship

Some have argued that hair pulling in trichotillomania (TTM) is triggered by traumatic events, but reliable evidence linking trauma to TTM is limited. However, research has shown that hair pulling is associated with emotion regulation, suggesting a connection between negative affect and TTM. We investigated the associations between trauma, negative affect, and hair pulling in a cross-sectional sample of treatment seeking adults with TTM (N=85). In the current study, participants’ self-reported traumatic experiences were assessed during a structured clinical interview, and participants completed several measures of hair pulling severity, global TTM severity, depression, anxiety, experiential avoidance, and quality of life. Those who experienced trauma had more depressive symptoms, increased experiential avoidance, and greater global TTM severity. Although the presence of a trauma history was not related to the severity of hair pulling symptoms in the past week, depressive symptoms mediated the relationship between traumatic experiences and global TTM severity. These findings cast doubt on the notion that TTM is directly linked to trauma, but suggest that trauma leads to negative affect that individuals cope with through hair pulling. Implications for the conceptualization and treatment of TTM are discussed

Recent Advances in Kinase Drug Discovery Part I: the Editors’ Take

This special issue on Advances in Kinase Drug Discovery provides a selection of research articles and topical reviews covering all aspects of drug discovery targeting the phosphotransferase enzyme family [...

Identification and characterization of an irreversible inhibitor of CDK2

Irreversible inhibitors that modify cysteine or lysine residues within a protein kinase ATP binding site offer, through their distinctive mode of action, an alternative to ATP-competitive agents. 4-((6-(Cyclohexylmethoxy)- 9H-purin-2-yl)amino)benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. Guided by the CDK2/NU6102 structure, we designed 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300), which binds covalently to CDK2 as shown by a co-complex crystal structure. Acute incubation with NU6300 produced a durable inhibition of Rb phosphorylation in SKUT-1B cells, consistent with it acting as an irreversible CDK2 inhibitor. NU6300 is the first covalent CDK2 inhibitor to be described, and illustrates the potential of vinyl sulfones for the design of more potent and selective compounds

Faint NUV/FUV Standards from Swift/UVOT, GALEX and SDSS Photometry

At present, the precision of deep ultraviolet photometry is somewhat limited by the dearth of faint ultraviolet standard stars. In an effort to improve this situation, we present a uniform catalog of eleven new faint (u sim17) ultraviolet standard stars. High-precision photometry of these stars has been taken from the Sloan Digital Sky Survey and Galaxy Evolution Explorer and combined with new data from the Swift Ultraviolet Optical Telescope to provide precise photometric measures extending from the Near Infrared to the Far Ultraviolet. These stars were chosen because they are known to be hot (20,000 < T_eff < 50,000 K) DA white dwarfs with published Sloan spectra that should be photometrically stable. This careful selection allows us to compare the combined photometry and Sloan spectroscopy to models of pure hydrogen atmospheres to both constrain the underlying properties of the white dwarfs and test the ability of white dwarf models to predict the photometric measures. We find that the photometry provides good constraint on white dwarf temperatures, which demonstrates the ability of Swift/UVOT to investigate the properties of hot luminous stars. We further find that the models reproduce the photometric measures in all eleven passbands to within their systematic uncertainties. Within the limits of our photometry, we find the standard stars to be photometrically stable. This success indicates that the models can be used to calibrate additional filters to our standard system, permitting easier comparison of photometry from heterogeneous sources. The largest source of uncertainty in the model fitting is the uncertainty in the foreground reddening curve, a problem that is especially acute in the UV.Comment: Accepted for publication in Astrophysical Journal. 31 pages, 13 figures, electronic tables available from ApJ or on reques

Results from the Supernova Photometric Classification Challenge

We report results from the Supernova Photometric Classification Challenge (SNPCC), a publicly released mix of simulated supernovae (SNe), with types (Ia, Ibc, and II) selected in proportion to their expected rate. The simulation was realized in the griz filters of the Dark Energy Survey (DES) with realistic observing conditions (sky noise, point-spread function and atmospheric transparency) based on years of recorded conditions at the DES site. Simulations of non-Ia type SNe are based on spectroscopically confirmed light curves that include unpublished non-Ia samples donated from the Carnegie Supernova Project (CSP), the Supernova Legacy Survey (SNLS), and the Sloan Digital Sky Survey-II (SDSS-II). A spectroscopically confirmed subset was provided for training. We challenged scientists to run their classification algorithms and report a type and photo-z for each SN. Participants from 10 groups contributed 13 entries for the sample that included a host-galaxy photo-z for each SN, and 9 entries for the sample that had no redshift information. Several different classification strategies resulted in similar performance, and for all entries the performance was significantly better for the training subset than for the unconfirmed sample. For the spectroscopically unconfirmed subset, the entry with the highest average figure of merit for classifying SNe~Ia has an efficiency of 0.96 and an SN~Ia purity of 0.79. As a public resource for the future development of photometric SN classification and photo-z estimators, we have released updated simulations with improvements based on our experience from the SNPCC, added samples corresponding to the Large Synoptic Survey Telescope (LSST) and the SDSS, and provided the answer keys so that developers can evaluate their own analysis.Comment: accepted by PAS

The effect of intervertebral cartilage on neutral posture and range of motion in the necks of sauropod dinosaurs

The necks of sauropod dinosaurs were a key factor in their evolution. The habitual posture and range of motion of these necks has been controversial, and computer-aided studies have argued for an obligatory sub-horizontal pose. However, such studies are compromised by their failure to take into account the important role of intervertebral cartilage. This cartilage takes very different forms in different animals. Mammals and crocodilians have intervertebral discs, while birds have synovial joints in their necks. The form and thickness of cartilage varies significantly even among closely related taxa. We cannot yet tell whether the neck joints of sauropods more closely resembled those of birds or mammals. Inspection of CT scans showed cartilage:bone ratios of 4.5% for Sauroposeidon and about 20% and 15% for two juvenile Apatosaurus individuals. In extant animals, this ratio varied from 2.59% for the rhea to 24% for a juvenile giraffe. It is not yet possible to disentangle ontogenetic and taxonomic signals, but mammal cartilage is generally three times as thick as that of birds. Our most detailed work, on a turkey, yielded a cartilage:bone ratio of 4.56%. Articular cartilage also added 11% to the length of the turkey's zygapophyseal facets. Simple image manipulation suggests that incorporating 4.56% of neck cartilage into an intervertebral joint of a turkey raises neutral posture by 15°. If this were also true of sauropods, the true neutral pose of the neck would be much higher than has been depicted. An additional 11% of zygapophyseal facet length translates to 11% more range of motion at each joint. More precise quantitative results must await detailed modelling. In summary, including cartilage in our models of sauropod necks shows that they were longer, more elevated and more flexible than previously recognised

Identification of a novel ligand for the ATAD2 bromodomain with selectivity over BRD4 through a fragment growing approach

Structure-guided expansion of a fragment hit for the ATAD2 bromodomain enabled improvement in ATAD2 inhibition and selectivity over BRD4.</p

Quantum nondemolition measurement of mechanical motion quanta

The fields of opto- and electromechanics have facilitated numerous advances in the areas of precision measurement and sensing, ultimately driving the studies of mechanical systems into the quantum regime. To date, however, the quantization of the mechanical motion and the associated quantum jumps between phonon states remains elusive. For optomechanical systems, the coupling to the environment was shown to preclude the detection of the mechanical mode occupation, unless strong single photon optomechanical coupling is achieved. Here, we propose and analyse an electromechanical setup, which allows to overcome this limitation and resolve the energy levels of a mechanical oscillator. We find that the heating of the membrane, caused by the interaction with the environment and unwanted couplings, can be suppressed for carefully designed electromechanical systems. The results suggest that phonon number measurement is within reach for modern electromechanical setups.Comment: 8 pages, 5 figures plus 24 pages, 11 figures supplemental materia

Patients with severe COVID-19 do not have elevated autoantibodies against common diagnostic autoantigens

Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative pathogen of coronavirus disease 2019 (COVID-19) presents occasionally with an aberrant autoinflammatory response, including the presence of elevated circulating autoantibodies in some individuals. Whether the development of autoantibodies against self-antigens affects COVID-19 outcomes remains unclear. To better understand the prognostic role of autoantibodies in COVID-19, we quantified autoantibodies against 23 markers that are used for diagnosis of autoimmune disease. To this end, we used serum samples from patients with severe [intensive care unit (ICU)] and moderate (ward) COVID-19, across two to six consecutive time points, and compared autoantibody levels to uninfected healthy and ICU controls. Acute and post-acute serum (from 1 to 26 ICU days) was collected from 18 ICU COVID-19-positive patients at three to six time points; 18 ICU COVID-19-negative patients (sampled on ICU day 1 and 3); 21 ward COVID-19-positive patients (sampled on hospital day 1 and 3); and from 59 healthy uninfected controls deriving from two cohorts. Levels of IgG autoantibodies against 23 autoantigens, commonly used for autoimmune disease diagnosis, were measured in serum samples using MSD® U-PLEX electrochemiluminescence technology (MSD division Meso Scale Discovery®), and results were compared between groups. There were no significant elevations of autoantibodies for any of the markers tested in patients with severe COVID-19. Sample collections at longer time points should be considered in future studies, for assessing the possible development of autoantibody responses following infection with SARS-CoV-2