CCD QE in the Soft X-ray Range

e2v has previously provided back-illuminated CCDs for several solar observation projects, resulting in a number of key articles on CCD QE in the soft X-ray region. To update these, e2v has arranged for tests on X-ray optimised EMCCDs at a synchrotron. These have shown QE of at least 45% from 40 eV to 2000 eV, with Enhanced process devices having significantly higher QE than Basic process. The measured values were similar to data published from the SDO SXI mission, showing that the e2v process has been stable over many years. The soft X-ray QE measurements show a reasonable fit to the simple layer model for energies > 600 eV. For energies < 100 eV, measurements show slightly lower QE than the model prediction for both Basic and Enhanced processes. For energies 100 eV to 600 eV, measurements show a reasonable fit to the model for the Basic process, but less improvement from the Enhanced process than the model predicts. Comparing the ~80% typical QE for UV-optimised CCDs at 385 nm with the 45% QE measured at 120 eV in this study, there is a discrepancy in QE for two photon energies with the same absorption length measured on CCDs from the same back-thinning process (one type with AR coating, one type without)

Why States Save: Using Evidence to Inform How Large Rainy Day Funds Should Grow

As revenue and spending pressures shift along with the booms and busts of the economy, states stand to benefit from the additional flexibility provided by robust rainy day funds to smooth over unexpected bumps in the road. But absent a clear purpose for saving, some states also find it extremely difficult to set a meaningful savings target, which can confound their efforts to manage the budgetary ups and downs of economic activity.This report examines how state policymakers should design their funds to help inform an optimal savings target. It analyzes existing guidelines -- set in statutory or constitutional language -- around the management of rainy day funds and offers key questions to consider while crafting such guidelines

Albumin Levels in Tear Film Modulate the Bioavailability of Medically-Relevant Topical Drugs

The breakdown of blood-tear barrier that occurs with ocular pathology allows for large amounts of albumin to leak into the tear fluid. This process likely represents an important restriction to drug absorption in ophthalmology, as only the unbound drug is transported across the ocular tissue barriers to exert its pharmacologic effect. We aimed to investigate the effects of albumin levels in tears on the bioavailability of two commonly used ophthalmic drugs: tropicamide, an antimuscarinic that produces mydriasis and cycloplegia, and latanoprost, a PGF2α analog used for the treatment of glaucoma. Eight female beagle dogs underwent a randomized, vehicle-controlled crossover trial. For each dog, one eye received 30 µl of artificial tears (control) or canine albumin (0.4 or 1.5%) at random, immediately followed by 30 µl of 1% tropicamide (2 days, 24 h washout) or 0.005% latanoprost (2 days, 72 h washout) in both eyes. Pupil diameter (digital caliper) and intraocular pressure (IOP; rebound tonometry) were recorded at various times following drug administration (0 to 480 min) and compared between both groups with a mixed model for repeated measures. Albumin in tears had a significant impact on pupillary diameter for both tropicamide (P ≤ 0.001) and latanoprost (P ≤ 0.047), with no differences noted between 0.4% and 1.5% concentrations. Reduction in the maximal effect (pupil size) and overall drug exposure (area under the effect time-curve of pupil size over time) were significant for tropicamide (6.2–8.5% on average, P ≤ 0.006) but not for latanoprost (P ≥ 0.663). The IOP, only measured in eyes receiving latanoprost, was not significantly impacted by the addition of either 0.4% (P = 0.242) or 1.5% albumin (P = 0.879). Albumin in tear film, previously shown to leak from the conjunctival vasculature in diseased eyes, may bind to topically administered drugs and reduces their intraocular penetration and bioavailability. Further investigations in clinical patients and other commonly used ophthalmic medications are warranted

Genetic diversity in the processing and transcriptomic diversity in the targeting of microRNAs

MicroRNAs are short RNA molecules that are central to the regulation of many cellular and developmental pathways. They are processed in several stages from structured precursors in the nucleus, into mature microRNAs in the cytoplasm where they direct protein complexes to regulate gene expression through, often imperfect base-pairing with target messenger RNAs. The broad aim of this project is to better understand how polymorphisms and new mutations can disrupt microRNA processing and targeting, and ultimately define their contributions to human disease. I have taken two approaches towards this. The first approach is to comprehensively identify the microRNA targets by developing and applying a novel computational pipeline to identify microRNA binding events genome-wide in RNA-RNA interaction datasets. I use this to examine the transcriptomic diversity of microRNA binding, finding microRNA binding events along the full length of protein coding transcripts and with a variety of non-coding RNAs. This reveals enrichment for non-canonical microRNA binding at promoters and intronic regions around splice sites, and identifies highly spatially clustered binding sites within transcripts that may be acting as competitive endogenous RNAs to compete for microRNAs, effectively sequestering them. Using statistical models and new cell fractionated RNA-seq data, I rank the features of microRNAs and their binding sites which contribute to the strength and specificity of their interaction to provide a better understanding of the major determinants of microRNA targeting. The second approach is to directly identify DNA sequence changes in microRNA precursors that alter processing efficiency affecting mature microRNA abundance which are routinely overlooked in the search for disease or trait associated causal variants. I have systematically screened public datasets for both rare and common polymorphisms that overlap microRNA precursors and are correlated with mature microRNA levels as measured in short RNA sequencing. I use these eQTL SNPs to examine the most important microRNA precursor regions and sequence motifs. Several of these SNPs have been observed as risk factors in cancer or other clinically relevant traits, and correlated with microRNA processing efficiency. I demonstrate that a specific DNA change which is known to be important in the development of some cancers, is located in a microRNA precursor and affects the balance of its two products, miR-146a-3p and miR-146a-5p, that can be produced from that single precursor providing new insights into the mechanisms of microRNA production and the aspects of genetic mis-regulation that result in cancer. I find further examples of common human polymorphisms that appear to affect microRNA production from their precursors, several of these variants are independently implicated in human immune disease, cancer susceptibility and associated with other complex traits. As they exhibit a molecular phenotype and immediately lead to mechanistic hypotheses of trait causality that can be tested, these variants could provide a route into the frequently intractable problem of mechanistically linking non-coding genetic variation to human phenotypes. Applying similar studies to patient DNA has revealed rare and unique DNA changes that are now candidates for causing human disease that are being subject to follow-up experimental studies. Collectively this work has started to define which sequences changes in microRNAs are likely to disrupt their function and provides a paradigm for the analysis of microRNA sequence variants in human genetic disease

Divided Government, Legislative Productivity, and Policy Change in the USA and France

The concept of “divided government” is more complicated than scholars have allowed. In the USA, truly unified government, where the president enjoys a filibuster-proof majority in the Senate as well as a majority in the House, is rare. In France, truly unified government has been more common, but divided government has also occurred several times. Democratic governance requires that parties address important issues and they do so regardless of the patterns of institutional control. Nevertheless, policy changes or important laws are affected by the higher level of institutional friction associated with divided government. Looking at both the USA and France, we find that periods of unified government show higher levels of production of important laws in the USA, but we find no difference for overall legislative productivity

Aortic calcification and femoral bone density are independently associated with left ventricular mass in patients with chronic kidney disease

Background Vascular calcification and reduced bone density are prevalent in chronic kidney disease and linked to increased cardiovascular risk. The mechanism is unknown. We assessed the relationship between vascular calcification, femoral bone density and left ventricular mass in patients with stage 3 non-diabetic chronic kidney disease in a cross-sectional observational study. Methodology and Principal Findings A total of 120 patients were recruited (54% male, mean age 55±14 years, mean glomerular filtration rate 50±13 ml/min/1.73 m2). Abdominal aortic calcification was assessed using lateral lumbar spine radiography and was present in 48%. Mean femoral Z-score measured using dual energy x-ray absorptiometry was 0.60±1.06. Cardiovascular magnetic resonance imaging was used to determine left ventricular mass. One patient had left ventricular hypertrophy. Subjects with aortic calcification had higher left ventricular mass compared to those without (56±16 vs. 48±12 g/m2, P = 0.002), as did patients with femoral Z-scores below zero (56±15 vs. 49±13 g/m2, P = 0.01). In univariate analysis presence of aortic calcification correlated with left ventricular mass (r = 0.32, P = 0.001); mean femoral Z-score inversely correlated with left ventricular mass (r = −0.28, P = 0.004). In a multivariate regression model that included presence of aortic calcification, mean femoral Z-score, gender and 24-hour systolic blood pressure, 46% of the variability in left ventricular mass was explained (P<0.001). Conclusions In patients with stage 3 non-diabetic chronic kidney disease, lower mean femoral Z-score and presence of aortic calcification are independently associated with increased left ventricular mass. Further research exploring the pathophysiology that underlies these relationships is warranted

Measuring the Effects of THC on Human Sperm Parameters Using Biomonitoring Analysis

Marijuana is one of the most common substances used in the United States with more men utilizing marijuana compared to women. The effects of marijuana on the brain are well known, however, there is limited research on its effects on human sperm parameters. We examined the association between THC and human sperm parameters in participants in the Washington D.C. area. Our preliminary results suggested that THC was associated with low sperm morphology. Background: Marijuana has a long history of human usage for medicinal, ceremonial, and religious purposes. As of January 2018, nine states including Washington D.C. have legalized it for recreational usage. Marijuana is considered one of the most commonly used illicit drugs in the United States with about 40-50% of adults having used it at least once. Estimates from 2017 suggest that 13% of men use marijuana regularly compared to 7% of women. While the effects of tetrahydrocannabinol (THC), the chemical found in marijuana, on the brain are well known; few studies have evaluated its effect on the male reproductive system. THC affects the endocannabinoid system, a biological system of endocannabinoids with receptors throughout the body responsible for maintaining homeostasis. Cannabinoids such as THC bind to cannabinoid receptors, altering their activity, and have been associated with low sperm concentration and sperm count that can ultimately lead to infertility. Objective: Examine associations between THC concentrations and semen quality including sperm motility, morphology, and concentration in the Washington D.C. area. Methods: Participants were recruited from the Men\u27s Health Study in the Washington D.C. area. Participants provided a urine and semen sample; completed a comprehensive questionnaire on lifestyle, medical history, and cannabis use. Sixty-two urine samples were sent to the laboratory at the University of Utah for analysis of the COOH-THC, the main THC metabolite. Semen analysis was completed at The Perry Laboratory at GWSPH examining sperm parameters such as morphology, concentration, and motility. Results: Our preliminary results show approximately 25% of samples had detectable levels of THC, and there is suggestive evidence that THC was associated with lower morphology

Hyb:A bioinformatics pipeline for the analysis of CLASH (crosslinking, ligation and sequencing of hybrids) data

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