Bitopic integral membrane proteins with a single transmembrane helix play diverse roles in catalysis, cell signaling, and morphogenesis. Complete monospanning protein structures are needed to show ...how interaction between the transmembrane helix and catalytic domain might influence association with the membrane and function. We report crystal structures of full-length Saccharomyces cerevisiae lanosterol 14αdemethylase, a membrane monospanning cytochrome P450 of the CYP51 family that catalyzes the first postcyclization step in ergosterol biosynthesis and is inhibited by triazole drugs. The structures reveal a well-ordered N-terminal amphipathic helix preceding a putative transmembrane helix that would constrain the catalytic domain orientation to lie partly in the lipid bilayer. The structures locate the substrate lanosterol, identify putative substrate and product channels, and reveal constrained interactions with triazole antifungal drugs that are important for drug design and understanding drug resistance.
As the main microtubule-organizing centre in animal cells, the centrosome has a fundamental role in cell function. Surrounding the centrioles, the pericentriolar material (PCM) provides a dynamic ...platform for nucleating microtubules. Although the importance of the PCM is established, its amorphous electron-dense nature has made it refractory to structural investigation. By using SIM and STORM subdiffraction-resolution microscopies to visualize proteins critical for centrosome maturation, we demonstrate that the PCM is organized into two main structural domains: a layer juxtaposed to the centriole wall, and proteins extending farther away from the centriole organized in a matrix. Analysis of Pericentrin-like protein (PLP) reveals that its carboxy terminus is positioned at the centriole wall, it radiates outwards into the matrix and is organized in clusters having quasi-nine-fold symmetry. By RNA-mediated interference (RNAi), we show that PLP fibrils are required for interphase recruitment and proper mitotic assembly of the PCM matrix.
Thirty years on, and the mechanism of superconductivity in copper-oxide superconductors remains a mystery. Knowledge of their normal nonsuperconducting state is also incomplete; however, we do know ...that the more robust the superconductivity, the higher the magnetic fields required to suppress it. Ramshaw et al. studied samples of three different compositions of the copper-oxide YBa2Cu3O6+δ in magnetic fields exceeding 90 T. They found that as the oxygen content increased toward the point of the maximum transition temperature, the conducting electrons became heavier and heavier. This mass enhancement reflected an increase in electronic correlations, which in turn may be a signature of a quantum critical point. Science, this issue p. 317 In the quest for superconductors with higher transition temperatures (Tc), one emerging motif is that electronic interactions favorable for superconductivity can be enhanced by fluctuations of a broken-symmetry phase. Recent experiments have suggested the existence of the requisite broken-symmetry phase in the high-Tc cuprates, but the impact of such a phase on the ground-state electronic interactions has remained unclear. We used magnetic fields exceeding 90 tesla to access the underlying metallic state of the cuprate YBa2Cu3O6+δ over a wide range of doping, and observed magnetic quantum oscillations that reveal a strong enhancement of the quasiparticle effective mass toward optimal doping. This mass enhancement results from increasing electronic interactions approaching optimal doping, and suggests a quantum critical point at a hole doping of pcrit approximate 0.18.
Purpose To evaluate the early implementation of synthesized two-dimensional (s2D) mammography in a population screened entirely with s2D and digital breast tomosynthesis (DBT) (referred to as ...s2D/DBT) and compare recall rates and cancer detection rates to historic outcomes of digital mammography combined with DBT (referred to as digital mammography/DBT) screening. Materials and Methods This was an institutional review board-approved and HIPAA-compliant retrospective interpretation of prospectively acquired data with waiver of informed consent. Compared were recall rates, biopsy rates, cancer detection rates, and radiation dose for 15 571 women screened with digital mammography/DBT from October 1, 2011, to February 28, 2013, and 5366 women screened with s2D/DBT from January 7, 2015, to June 30, 2015. Two-sample z tests of equal proportions were used to determine statistical significance. Results Recall rate for s2D/DBT versus digital mammography/DBT was 7.1% versus 8.8%, respectively (P < .001). Biopsy rate for s2D/DBT versus digital mammography/DBT decreased (1.3% vs 2.0%, respectively; P = .001). There was no significant difference in cancer detection rate for s2D/DBT versus digital mammography/DBT (5.03 of 1000 vs 5.45 of 1000, respectively; P = .72). The average glandular dose was 39% lower in s2D/DBT versus digital mammography/DBT (4.88 mGy vs 7.97 mGy, respectively; P < .001). Conclusion Screening with s2D/DBT in a large urban practice resulted in similar outcomes compared with digital mammography/DBT imaging. Screening with s2D/DBT allowed for the benefits of DBT with a decrease in radiation dose compared with digital mammography/DBT.
RSNA, 2016 An earlier incorrect version of this article appeared online. This article was corrected on August 11, 2016.
Dielectric breakdown strength is one of the critical performance metrics for pure gases and gas mixtures used in large, high pressure gas time projection chambers. In this paper we experimentally ...study dielectric breakdown strengths of several important time projection chamber working gases and gas-phase insulators over the pressure range 100 mbar to 10 bar, and gap sizes ranging from 0.1 to 10 mm. Gases characterized include argon, xenon, CO
2
, CF
4
, and mixtures 90-10 argon-CH
4
, 90-10 argon-CO
2
and 99-1 argon-CF
4
. We develop a theoretical model for high voltage breakdown based on microphysical simulations that use PyBoltz electron swarm Monte Carlo results as input to Townsend- and Meek-like discharge criteria. This model is shown to be highly predictive at high pressure, out-performing traditional Paschen–Townsend and Meek–Raether models significantly. At lower pressure-times-distance, the Townsend-like model is an excellent description for noble gases whereas the Meek-like model provides a highly accurate prediction for insulating gases.
ABSTRACT
We report the detection of radio emission from the known X-ray flaring star EXO 040830−7134.7 during Karoo Array Telescope (MeerKAT) observations of the nearby cataclysmic variable VW Hydri. ...We have three epochs of MeerKAT observations, where the star is not detected in the first epoch, is detected in the second epoch, and is marginally detected in the third epoch. We cannot distinguish whether the detection is quiescent emission or a transient radio burst. If we assume that the radio detection is quiescent emission, the source lies somewhat to the right of the Güdel–Benz relation; however, if we assume that the upper limit on the radio non-detection is indicative of the quiescent emission, then the source lies directly on the relation. Both cases are broadly consistent with the relation. We use archival spectral energy distribution data and new Southern African Large Telescope high-resolution spectroscopy to confirm that EXO 040830−7134.7 is a chromospherically active M-dwarf with a temperature of 4000 ± 200 K of spectral type M0V. We use All-Sky Automated Survey (ASAS), All-Sky Automated Survey for Supernovae (ASAS-SN), and Transiting Exoplanet Survey Satellite (TESS) optical photometry to derive an improved rotational period of 5.18 ± 0.04 d. This is the first radio detection of the source, and the first MeerKAT detection of an M-dwarf.
Abstract Background Unicompartmental knee arthroplasty (UKA) has gained popularity in patients with isolated unicompartmental osteoarthritis. To our knowledge no systematic review has assessed and ...compared survivorship of medial and lateral UKA. We performed a systematic review assessing medial and lateral UKA survivorship and comparing survivorship in cohort studies and registry-based studies. Methods A search was performed using PubMed, Embase and Cochrane systems. Ninety-six eligible studies reported survivorship, of which fifty-eight reported medial and sixteen reported lateral UKA survivorship. Nineteen cohort studies and seven registry-based studies reported combined medial and lateral survivorship. Results The five-year, ten-year and fifteen-year medial UKA survivorship was 93.9%, 91.7% and 88.9%, respectively. Lateral UKA survivorship was 93.2%, 91.4% and 89.4% at five-year, ten-year and fifteen-year, respectively. No statistical difference between both compartments was found. At twenty years and twenty-five years survivorship of medial UKA was 84.7% and 80%, respectively, but no studies reported lateral UKA survivorship at these follow-up intervals. Survivorship of cohort studies was not significantly higher compared to registry-based studies at five years (94.3 vs. 91.7, respectively, p = 0.133) but was significantly higher at ten years (90.5 vs. 84.1, p = 0.015). Conclusion This is the first systematic review that shows no difference in the five-, ten- and fifteen-year survivorship of medial and lateral UKA. We found a lower survivorship in the registry-based studies compared to cohort studies. Level of evidence Systematic Review of level IV studies.
Chromosome 22q11.2 deletion syndrome (22q11DS) is a common genetic disorder with high rates of psychosis and other psychopathologies, but few studies discuss treatment. Our aim was to characterize ...the prevalence and treatment of major psychiatric illnesses in a well-characterized sample of individuals with 22q11DS.
This was a cross-sectional study of 112 individuals aged 8 to 45 years with a confirmed diagnosis of 22q11DS. Each participant was administered a modified Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) and the Structured Interview for Prodromal Syndromes (SIPS). Phenotypes assessed were threshold and subthreshold psychosis, depression, mania, generalized and separation anxiety, obsessions/compulsions, inattention/hyperactivity and substance use. Histories of mental health care and current psychotropic treatment were obtained.
Psychopathology was common, with 79% of individuals meeting diagnostic criteria for a disorder at the time of assessment. Diagnoses of psychosis were made in 11% of cases, attenuated positive symptom syndrome (APS) in 21%, and 47% experienced significant subthreshold symptoms. Peak occurrence of psychosis risk was during adolescence (62% of those aged 12-17 years). Criteria for a mood disorder were met by 14%, for anxiety disorder 34% and for attention deficit hyperactivity disorder (ADHD) 31%. Mental health care had been received by 63% of individuals in their lifetime, but only 40% continued therapy and 39% used psychotropics. Antipsychotics were used by 42% of participants with psychosis and none of the participants with APS. Half of those at risk for psychosis were receiving no mental health care.
Psychopathology is common in 22q11DS but is not adequately treated or clinically followed. Particular attention should be paid to subthreshold psychotic symptoms, especially in adolescents.
The nature of the neutrino is one of the major open questions in experimental nuclear and particle physics. The most sensitive known method to establish the Majorana nature of the neutrino is ...detection of the ultra-rare process of neutrinoless double beta decay. However, identification of one or a handful of decay events within a large mass of candidate isotope, without obfuscation by backgrounds is a formidable experimental challenge. One hypothetical method for achieving ultra- low-background neutrinoless double beta decay sensitivity is the detection of single
Ba ions produced in the decay of
Xe ("barium tagging"). To implement such a method, a single-ion-sensitive barium detector must be developed and demonstrated in bulk liquid or dry gaseous xenon. This paper reports on the development of two families of dry-phase barium chemosensor molecules for use in high pressure xenon gas detectors, synthesized specifically for this purpose. One particularly promising candidate, an anthracene substituted aza-18-crown-6 ether, is shown to respond in the dry phase with almost no intrinsic background from the unchelated state, and to be amenable to barium sensing through fluorescence microscopy. This interdisciplinary advance, paired with earlier work demonstrating sensitivity to single barium ions in solution, opens a new path toward single ion detection in high pressure xenon gas.
Close to optimal doping, the copper oxide superconductors show 'strange metal' behaviour, suggestive of strong fluctuations associated with a quantum critical point. Such a critical point requires a ...line of classical phase transitions terminating at zero temperature near optimal doping inside the superconducting 'dome'. The underdoped region of the temperature-doping phase diagram from which superconductivity emerges is referred to as the 'pseudogap' because evidence exists for partial gapping of the conduction electrons, but so far there is no compelling thermodynamic evidence as to whether the pseudogap is a distinct phase or a continuous evolution of physical properties on cooling. Here we report that the pseudogap in YBa2Cu3O6+δ is a distinct phase, bounded by a line of phase transitions. The doping dependence of this line is such that it terminates at zero temperature inside the superconducting dome. From this we conclude that quantum criticality drives the strange metallic behaviour and therefore superconductivity in the copper oxide superconductors.
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