Cardio-Protection Afforded by Β-Blockade Is Maintained During Resistance Exercise

Objectives Whether or not the cardio-protective effect of β-adrenergic blockade is retained during resistance exercise has not been systematically evaluated. Therefore the purpose of this study was to measure selected cardiorespiratory responses to isometric exercise involving hand-gripping, single-leg extension, or double-leg dead-lift, under placebo (control), β1-selective (atenolol), and non-selective (propranolol) adrenergic blockade conditions. Design Eleven young male adults were evaluated in a randomized, double-blinded, repeated measures study design and performed all three exercise modalities at 30% of maximal voluntary contraction under placebo, atenolol and propranolol conditions. Methods Heart rate, systolic and diastolic blood pressure, rate-pressure product, oxygen uptake, cardiac output, stroke volume and total peripheral resistance were directly measured or calculated at rest and during the third minute of each of the three exercise modes. Results Irrespective of drug condition, a graded pressor response was observed going from rest to exercise so that rest \u3c handgrip \u3c leg extension \u3c dead-lift for heart rate, systolic and diastolic blood pressures, rate-pressure product and oxygen uptake (p \u3c 0.05 for all). Cardiac output only increased with the dead-lift mode of exercise (p \u3c 0.01). Importantly β-adrenergic blockade with either atenolol or propranolol similarly attenuated the rise in heart rate, and systolic blood pressure; thus rate-pressure product demonstrated a mode-of-exercise by drug interaction effect (p \u3c 0.001) with the greatest reductions seen with the dead-lift procedure. Conclusions The findings indicate that cardio-protection afforded by selective or non-selective β-blockade at rest is preserved during isometric exercise and even enhanced once heart rate increases above 100 beats min−1

Non-Parametric Estimation of Forecast Distributions in Non-Gaussian, Non-linear State Space Models

The object of this paper is to produce non-parametric maximum likelihood estimates of forecast distributions in a general non-Gaussian, non-linear state space setting. The transition densities that define the evolution of the dynamic state process are represented in parametric form, but the conditional distribution of the non-Gaussian variable is estimated non-parametrically. The filtering and prediction distributions are estimated via a computationally efficient algorithm that exploits the functional relationship between the observed variable, the state variable and a measurement error with an invariant distribution. Simulation experiments are used to document the accuracy of the non-parametric method relative to both correctly and incorrectly specified parametric alternatives. In an empirical illustration, the method is used to produce sequential estimates of the forecast distribution of realized volatility on the S&P500 stock index during the recent financial crisis. A resampling technique for measuring sampling variation in the estimated forecast distributions is also demonstrated.Probabilistic Forecasting; Non-Gaussian Time Series; Grid-based Filtering; Penalized Likelihood; Subsampling; Realized Volatility.

Pulsar Wind Nebulae in EGRET Error Boxes

A remarkable number of pulsar wind nebulae (PWN) are coincident with EGRET gamma-ray sources. X-ray and radio imaging studies of unidentified EGRET sources have resulted in the discovery of at least 6 new pulsar wind nebulae (PWN). Stationary PWN (SPWN) appear to be associated with steady EGRET sources with hard spectra, typical for gamma-ray pulsars. Their toroidal morphologies can help determine the geometry of the pulsar which is useful for constraining models of pulsed gamma-ray emission. Rapidly moving PWN (RPWN) with more cometary morphologies seem to be associated with variable EGRET sources in regions where the ambient medium is dense compared to what is typical for the ISM.Comment: 8 pages, 5 figures, to appear in the proceedings of "The Multiwavelength Approach to Unidentified Sources", ed. G. Romero & K.S. Chen

Broadband Infrared Photodetection Using a Narrow Bandgap Conjugated Polymer

Photodetection spanning the short-, mid-, and long-wave infrared (SWIR-LWIR) underpins modern science and technology. Devices using state-of-the-art narrow bandgap semiconductors require complex manufacturing, high costs, and cooling requirements that remain prohibitive for many applications. We report high-performance infrared photodetection from a donor-acceptor conjugated polymer with broadband SWIR-LWIR operation. Electronic correlations within the π-conjugated backbone promote a high-spin ground state, narrow bandgap, long-wavelength absorption, and intrinsic electrical conductivity. These previously unobserved attributes enabled the fabrication of a thin-film photoconductive detector from solution, which demonstrates specific detectivities greater than 2.10 × 109 Jones. These room temperature detectivities closely approach those of cooled epitaxial devices. This work provides a fundamentally new platform for broadly applicable, low-cost, ambient temperature infrared optoelectronics

Topological Superconductivity in Multifold Fermion Metals

Recently, multifold fermions characterized by band crossings with multifold degeneracy and Fermi surfaces with nontrivial Chern numbers have been discovered experimentally in AlPt[arXiv:1812.03310] and XSi(X=Rh,Co)[arXiv:1812.04466][arXiv:1901.03358][arXiv:1809.01312]. In this work, we largely expand the family of multifold fermion materials by pointing out that several well-studied noncentrosymmetric superconductors are indeed multifold fermion metals. Importantly, their normal state topological properties, which have been ignored in previous studies, play an important role in the superconducting properties. Taking Li$_2$Pd$_3$B and Li$_2$Pt$_3$B as examples, we found a large number of unconventional degenerate points, such as double spin-1, spin-3/2, Weyl and double Weyl topological band crossing points near the Fermi energy, which result in finite Chern numbers on Fermi surfaces. Long Fermi arc states in Li$_2$Pd$_3$B, originating from the nontrivial band topology were found. Importantly, it has been shown experimentally that Li$_2$Pd$_3$B and Li$_2$Pt$_3$B are fully gapped and gapless superconductors, respectively. By analyzing the possible pairing symmetries, we suggest that Li$_2$Pd$_3$B can be a DIII class topological superconductor with Majorana surface states, even though the spin-orbit coupling in Li$_2$Pd$_3$B is negligible. Interestingly, Li$_2$Pt$_3$B, being gapless, is likely to be a nodal topological superconductor with dispersionless surface Majorana modes. We further identified that several noncentrosymmetric superconductors, such as Mo$_3$Al$_2$C, PdBiSe, Y$_2$C$_3$ and La$_2$C$_3$, are multifold fermion superconductors whose normal state topological properties have been ignored in previous experimental and theoretical studies

Ultrafast High-Energy Micro-Supercapacitors Based On Open-Shell Polymer-Graphene Composites

Micro-supercapacitors are poised to serve as on-chip power sources for electronics. However, the challenge to simultaneously increase their power, energy, and lifetime demands new material combinations beyond current carbon-based systems. Here, we demonstrate that electro-deposition of an open-shell conjugated polymer with reduced graphene oxide achieves electrodes with capacitance up to 186 mF cm−2 (372 F cm−3). The extended delocalization within the open-shell polymer stabilizes redox states and facilitates a 3 V wide potential window, while the hierarchical electrode structure promotes ultrafast kinetics. The micro-supercapacitor shows a high power density of 227 mW cm−2 with an energy density of 10.5 μWh cm−2 and stability of 84% capacitance retention after 11,000 cycles. These attributes allow operation at 120 Hz for fast charging and alternating current (AC) line filtering applications, which may be suitable to replace bulky electrolytic capacitors or serve as high-endurance energy storage for wireless electronics

Endometriosis and chronic pelvic pain have similar impact on women, but time to diagnosis is decreasing : an Australian survey

Chronic pelvic pain (CPP) affects a significant number of women worldwide. Internationally, people with endometriosis report significant negative impact across many areas of their life. We aimed to use an online survey using the EndoCost tool to determine if there was any difference in the impact of CPP in those with vs. those without a confirmed diagnosis of endometriosis, and if there was any change in diagnostic delay since the introduction of clinical guidelines in 2005. 409 responses were received; 340 with a diagnosis of endometriosis and 69 with no diagnosis. People with CPP, regardless of diagnosis, reported moderate to severe dysmenorrhea and non-cyclical pelvic pain. Dyspareunia was also common. Significant negative impact was reported for social, academic, and sexual/romantic relationships in both cohorts. In the endometriosis cohort there was a mean diagnostic delay of eight years, however there was a reduction in both the diagnostic delay (p < 0.001) and number of doctors seen before diagnosis (p < 0.001) in those presenting more recently. Both endometriosis and CPP have significant negative impact. Whilst there is a decrease in the time to diagnosis, there is an urgent need for improved treatment options and support for women with the disease once the diagnosis is made

Development of a Grp94 inhibitor

This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ja303477g.Heat shock protein 90 (Hsp90) represents a promising therapeutic target for the treatment of cancer and other diseases. Unfortunately, results from clinical trials have been disappointing as off-target effects and toxicities have been observed. These detriments may be a consequence of pan-Hsp90 inhibition, as all clinically evaluated Hsp90 inhibitors simultaneously disrupt all four human Hsp90 isoforms. Using a structure-based approach, we designed an inhibitor of Grp94, the ER-resident Hsp90. The effect manifested by compound 2 on several Grp94 and Hsp90α/β (cytosolic isoforms) clients were investigated. Compound 2 prevented intracellular trafficking of the Toll receptor, inhibited the secretion of IGF-II, affected the conformation of Grp94, and suppressed Drosophila larval growth, all Grp94-dependent processes. In contrast, compound 2 had no effect on cell viability or cytosolic Hsp90α/β client proteins at similar concentrations. The design, synthesis, and evaluation of 2 are described herein

Effects of a high-prebiotic diet versus probiotic supplements versus synbiotics on adult mental health : the "gut feelings" randomised controlled trial

Background: Preliminary evidence supports the use of dietary interventions and gut microbiota-targeted interventions such as probiotic or prebiotic supplementation for improving mental health. We report on the first randomised controlled trial (RCT) to examine the effects of a high-prebiotic dietary intervention and probiotic supplements on mental health. Methods: “Gut Feelings” was an 8-week, 2 × 2 factorial RCT of 119 adults with moderate psychological distress and low prebiotic food intake. Treatment arms: (1) probiotic supplement and diet-as-usual (probiotic group); (2) high-prebiotic diet and placebo supplement (prebiotic diet group); (3) probiotic supplement and high-prebiotic diet (synbiotic group); and (4) placebo supplement and diet-as-usual (placebo group). The primary outcome was assessment of total mood disturbance (TMD; Profile of Mood States Short Form) from baseline to 8 weeks. Secondary outcomes included anxiety, depression, stress, sleep, and wellbeing measures. Results: A modified intention-to-treat analysis using linear mixed effects models revealed that the prebiotic diet reduced TMD relative to placebo at 8 weeks [Cohen’s d = −0.60, 95% confidence interval (CI) = −1.18, −0.03; p = 0.039]. There was no evidence of symptom improvement from the probiotic (d = −0.19, 95% CI = −0.75, 0.38; p = 0.51) or synbiotic treatments (d = −0.03, 95% CI = −0.59, 0.53; p = 0.92). Improved anxiety, stress, and sleep were noted in response to the prebiotic diet while the probiotic tentatively improved wellbeing, relative to placebo. No benefit was found in response to the synbiotic intervention. All treatments were well tolerated with few adverse events. Conclusion: A high-prebiotic dietary intervention may improve mood, anxiety, stress, and sleep in adults with moderate psychological distress and low prebiotic intake. A synbiotic combination of high-prebiotic diet and probiotic supplement does not appear to have a beneficial effect on mental health outcomes, though further evidence is required. Results are limited by the relatively small sample size

Response of the Aerodyne Aerosol Mass Spectrometer to Inorganic Sulfates and Organosulfur Compounds: Applications in Field and Laboratory Measurements

Organosulfur compounds are important components of secondary organic aerosols (SOA). While the Aerodyne high-resolution time-of-flight aerosol mass spectrometer (AMS) has been extensively used in aerosol studies, the response of the AMS to organosulfur compounds is not well-understood. Here, we investigated the fragmentation patterns of organosulfurs and inorganic sulfates in the AMS, developed a method to deconvolve total sulfate into components of inorganic and organic origins, and applied this method in both laboratory and field measurements. Apportionment results from laboratory isoprene photooxidation experiment showed that with inorganic sulfate seed, sulfate functionality of organic origins can contribute ∼7% of SOA mass at peak growth. Results from measurements in the Southeastern U.S. showed that 4% of measured sulfate is from organosulfur compounds. Methanesulfonic acid was estimated for measurements in the coastal and remote marine boundary layer. We explored the application of this method to unit mass-resolution data, where it performed less well due to interferences. Our apportionment results demonstrate that organosulfur compounds could be a non-negligible source of sulfate fragments in AMS laboratory and field data sets. A reevaluation of previous AMS measurements over the full range of atmospheric conditions using this method could provide a global estimate/constraint on the contribution of organosulfur compounds