Observation of Radar Echoes from High-Energy Particle Cascades.

We report the observation of radar echoes from the ionization trails of high-energy particle cascades. Data were taken at the SLAC National Accelerator Laboratory, where the full electron beam (∼10^{9} e^{-} at ∼10 GeV/e^{-}) was directed into a plastic target to simulate an ultrahigh-energy neutrino interaction. The target was interrogated with radio waves, and coherent radio reflections from the cascades were detected with properties consistent with theoretical expectations. This is the first definitive observation of radar echoes from high-energy particle cascades, which may lead to a viable neutrino detection technology for energies ≳10^{16} eV.

Dynamic wetting of imidazolium-based ionic liquids on gold and glass.

Many of the applications of ionic liquids rely on their bulk properties or their solvation abilities. However, it is their interactions with solid surfaces that underpin many of their potential applications in advanced technologies. Whether it is as lubricants for wind turbines or as electrolytes in supercapacitors, there are many areas where ionic liquids can provide an improvement in performance relative to more commonplace liquids. However, there are some barriers to their implementation in such applications. Foremost of these is the lack of systematic studies of their interactions with solid surfaces as well as neglecting the effect of the absorbed water on wetting. The present study explores the dynamic wetting of three ionic liquids (with a different length of hydrocarbon chain in the cation) on gold and glass substrates, both of which are relevant for nano- and micromechanical machine applications, under well-controlled environmental conditions. The form of data capture (Wilhelmy plate) allows for a direct analysis using analytical expressions for the two dominant approaches for dynamic wetting: the hydrodynamic and molecular kinetic models. All ionic liquids yield data that are described best by the molecular kinetic model. Substrate-ionic liquid and water-ionic liquid interactions contribute to the mechanisms involved in the wetting process.

A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough.

The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagnosed with ACEi-induced cough. Controls were subjects with at least 6 months of ACEi use and no cough. A GWAS (1595 cases and 5485 controls) identified associations on chromosome 4 in an intron of KCNIP4. The strongest association was at rs145489027 (minor allele frequency=0.33, odds ratio (OR)=1.3 (95% confidence interval (CI): 1.2-1.4), P=1.0 × 10(-8)). Replication for six single-nucleotide polymorphisms (SNPs) in KCNIP4 was tested in a second eMERGE population (n=926) and in the Genetics of Diabetes Audit and Research in Tayside, Scotland (GoDARTS) cohort (n=4309). Replication was observed at rs7675300 (OR=1.32 (1.01-1.70), P=0.04) in eMERGE and at rs16870989 and rs1495509 (OR=1.15 (1.01-1.30), P=0.03 for both) in GoDARTS. The combined association at rs1495509 was significant (OR=1.23 (1.15-1.32), P=1.9 × 10(-9)). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk.

Provider perceptions of the value of same-day, electronic patient-reported measures for use in clinical HIV care.

Strong evidence suggests that patient-reported outcomes (PROs) aid in managing chronic conditions, reduce omissions in care, and improve patient-provider communication. However, provider acceptability of PROs and their use in clinical HIV care is not well known. We interviewed providers (n = 27) from four geographically diverse HIV and community care clinics in the US that have integrated PROs into routine HIV care, querying perceived value, challenges, and use of PRO data. Perceived benefits included the ability of PROs to identify less-observable behaviors and conditions, particularly suicidal ideation, depression, and substance use; usefulness in agenda setting prior to a visit; and reduction of social desirability bias in patient-provider communication. Challenges included initial flow integration issues and ease of interpretation of PRO feedback. Providers value same-day, electronic patient-reported measures for use in clinical HIV care with the condition that PROs are (1) tailored to be the most clinically relevant to their population; (2) well integrated into clinic flow; and (3) easy to interpret, highlighting chief patient concerns and changes over time.

Inhibition of stearoyl-CoA desaturase-1 in differentiating 3T3-L1 preadipocytes upregulates elongase 6 and downregulates genes affecting triacylglycerol synthesis.

BACKGROUND: Stearoyl-CoA desaturase-1 (SCD1) is rate limiting for the conversion of saturated fatty acids palmitate (16:0) and stearate (18:0) to monounsaturated fatty acids palmitoleate (16:1n7) and oleate (18:1n9), respectively. Given that reduced SCD1 activity is associated with improved insulin sensitivity and decreased body weight, there is considerable interest to elucidate the role of this enzyme in adipocytes. During adipogenesis, SCD1 levels increase concomitantly with the accumulation of triacylglycerol (TG); however, the extent to which reduced SCD1 activity can influence TG synthesis and metabolic pathways in differentiating adipocytes remains relatively unexplored. OBJECTIVE: The aim of this work was to delineate how reduced SCD1 activity affects gene expression, protein content and cellular fatty acids in differentiating murine preadipocytes. METHODS: 3T3-L1 preadipocytes were treated with an SCD1 inhibitor (10 nM) throughout differentiation. After 7 days, global gene expression, protein content and fatty acid profiles were examined using microarrays, western blotting and gas chromatography, respectively. RESULTS: SCD1 inhibition increased the abundance of 16:0 and 18:0 (45% and 194%, respectively) and decreased 16:1n7 and 18:1n7 (61% and 35%, respectively) in differentiated preadipocytes. Interestingly, 18:1n9 levels increased by 61%. The augmented 18:0 suggested a possible increase in elongase activity. Elongase 6 (Elovl6) gene expression was increased 2.8-fold (P = 0.04); however, changes were not detected for ELOVL6 protein content. Microarray analysis revealed that genes affecting TG synthesis were downregulated with SCD1 inhibition, which coincided with a 33% decrease in cellular TG content. CONCLUSION: These results provide new mechanistic insight into the role of SCD1 as a regulator of fatty acid profiles and TG synthesis in adipocytes, and reinforce that modulating SCD1 activity may help reduce the risk of obesity-related complications.

Dynamics of capillary-driven liquid-liquid displacement in open microchannels.

The dynamics of the spontaneous spreading of a liquid droplet along an open hydrophilic microchannel filled with another immiscible liquid is primarily determined by the competition between the capillary driving force and the viscous drag. While the former force depends on the channel cross-section and dimensions, interfacial tension between two liquids and the contact angle formed between the channel's wall and the two liquids, the latter arises from the motion of fluid molecules in the two bulk liquids. This paper focuses on the influence of the outer (displaced) phase viscosity. In general, as the viscosity of the displaced phase increases relative to the viscosity of the displacing phase, the velocity of the liquid-liquid meniscus decreases. The experiments were interpreted by extending a previously established correlation for liquid-vapour systems (J. Phys. Chem. C, 2011, 115(38), 18761-18769) in open microchannels of the same geometry. The relationship between the liquid-liquid flow dynamics and the properties of the liquids (e.g. viscosities) is still unclear. Nonetheless, by taking a self-consistent empirical approach to estimate the influence of the viscosities on the flow kinetics for a given system, it is possible to obtain a reasonable theoretical description for the experimental system over a specific range of viscosity ratios.

Phoretic motion of spheroidal particles due to self-generated solute gradients.

We study theoretically the phoretic motion of a spheroidal particle, which generates solute gradients in the surrounding unbounded solvent via chemical reactions active on its surface in a cap-like region centered at one of the poles of the particle. We derive, within the constraints of the mapping to classical diffusio-phoresis, an analytical expression for the phoretic velocity of such an object. This allows us to analyze in detail the dependence of the velocity on the aspect ratio of the polar and the equatorial diameters of the particle and on the fraction of the particle surface contributing to the chemical reaction. The particular cases of a sphere and of an approximation for a needle-like particle, which are the most common shapes employed in experimental realizations of such self-propelled objects, are obtained from the general solution in the limits that the aspect ratio approaches one or becomes very large, respectively.

Achieving a high-performance health care system with universal access: what the United States can learn from other countries.

This position paper concerns improving health care in the United States. Unlike previous highly focused policy papers by the American College of Physicians, this article takes a comprehensive approach to improving access, quality, and efficiency of care. The first part describes health care in the United States. The second compares it with health care in other countries. The concluding section proposes lessons that the United States can learn from these countries and recommendations for achieving a high-performance health care system in the United States. The articles are based on a position paper developed by the American College of Physicians' Health and Public Policy Committee. This policy paper (not included in this article) also provides a detailed analysis of health care systems in 12 other industrialized countries. Although we can learn much from other health systems, the College recognizes that our political and social culture, demographics, and form of government will shape any solution for the United States. This caution notwithstanding, we have identified several approaches that have worked well for countries like ours and could probably be adapted to the unique circumstances in the United States.

Pandemic influenza A(H1N1)v viruses currently circulating in New Zealand are sensitive to oseltamivir.

New Zealand, like other southern hemisphere countries with a temperate climate, has been in the winter period with seasonal influenza activity. New Zealand has also experienced a dramatic increase in the number of cases of pandemic influenza A(H1N1)v virus. Early reports from the northern hemisphere at the beginning of the pandemic showed that the virus was sensitive to the antiviral drug oseltamivir. In this study we report that pandemic influenza A(H1N1)v viruses currently circulating in New Zealand are sensitive to oseltamivir, but seasonal influenza A(H1N1) viruses - the co-circulating predominant seasonal strain, is resistant to oseltamivir.

Influence of very small bubbles on particle/bubble heterocoagulation.

Very small bubbles which partially coat the surface of particles influence whether or not heterocoagulation between a particle and a bubble occurs. The electrostatic and van der Waals forces of interaction between particles and bubbles were calculated as a function of electrolyte concentration, particle size, and the size and distributions of these very small bubbles present on the particle surface. The height of the surface force barrier was compared with the hydrodynamic pressing force under conditions of flotation. The presence of these very small bubbles has a profound effect on the interaction between particles and bubbles and, in particular, strongly decreases the critical particle radius for heterocoagulation.

Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network.

Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE-PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of "precision medicine." The February 2015 eMERGE-PGx data release includes sequence-derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation-Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.

Aprophen: a substrate and inhibitor of butyrylcholinesterase and carboxylesterases.

Aprophen, alpha-methyl-alpha-phenylbenzeneacetic acid-2-(diethylamino) ethyl ester, is a potent reversible inhibitor and a poor substrate of human serum butyrylcholinesterase (BuChE). Complex mixed competitive noncompetitive inhibition kinetics were observed; an apparent competitive inhibition constant was estimated to be 3.7 X 10(-7) M. BuChE hydrolysis of aprophen to diphenylpropionic acid and diethylaminoethanol did not appear to follow Michaelis-Menten kinetics. The BuChE turnover number for aprophen was 2.0 X 10(-3) sec-1. Rabbit liver oligomeric and monomeric carboxylesterases (CE) also hydrolyzed aprophen with a similar turnover number that varied from 1.4 X 10(-3) sec-1 to 4.3 X 10(-4) sec-1 respectively. Comparison of the catalytic rate of aprophen hydrolysis with butyrylthiocholine (BTC) and the neutral aromatic substrate, phenylthiobutyrate (phi TB), indicated that BuChE hydrolyzed BTC and phi TB 3.2 X 10(5) and 3.1 X 10(5) times more rapidly than aprophen respectively. Similarly, the CEs also hydrolyzed BTC and phi TB 17.6 and 1.9 X 10(5) times rapidly than aprophen. Acetylcholinesterases from bovine erythrocyte and electric eel were not inhibited by aprophen nor was aprophen hydrolyzed by these enzymes. The hydrolysis and inhibition reactions may best be described by a complex reaction scheme involving multiple binding sites for both the substrate and the inhibitor as well as positive cooperative ligand binding.

Cutaneous reactions to anticonvulsant medications.

Skin eruptions are an important consideration for any clinician who prescribes anticonvulsant medications. The timely recognition and accurate diagnosis of cutaneous reactions can prevent potentially fatal reactions and affect subsequent anticonvulsant treatment options. This review addresses the most common and most serious cutaneous reactions to anticonvulsant medications. The anticonvulsant hypersensitivity syndrome and individual antiepileptic medications that cause severe skin reactions will be reviewed. These reactions include morbilliform and urticarial drug eruptions as well as the erythema multiforme spectrum.

Loss in pattern-elicited electroretinograms in optic nerve dysfunction.

Both flash- and pattern-elicited electroretinograms and visual-evoked potentials were recorded from a patient with well-documented unilateral optic nerve dysfunction. Although the flash-elicited electroretinograms from the left and right eyes did not differ in amplitude or latency, the flash-elicited visual-evoked potentials were greatly attenuated. Prominent pattern-elicited electroretinograms and visual-evoked potentials, were recorded from the better eye, but neither could be obtained from the affected eye. These results supported the contention that pattern-elicited electroretinograms are derived from optic nerve activity and that the absence of such responses may be diagnostic of loss of optic nerve function. This suggests that testing protocols aimed at assessing optic nerve function might benefit from the inclusion of pattern-elicited electroretinographic recordings. We also obtained contrast sensitivity functions from both eyes. Although considerably suppressed, the contrast sensitivity of the affected eye exhibited a 3-octave range, indicating some pattern-processing capability.

Congenital toxoplasmic retinochoroiditis in the mouse--the use of the peroxidase anti-peroxidase method to demonstrate Toxoplasma antigen.

The peroxidase anti-peroxidase immunocytochemical staining method has been used to demonstrate Toxoplasma antigen within paraffin-embedded sections of the eyes of mice congenitally infected with Toxoplasma. Intact Toxoplasma tissue cysts were demonstrated within the retina but in no other ocular structure. No endozoites and no extra-cystic antigens were detected by this technique within any of the eyes examined. The possible implications of these findings in relation to the pathogenesis of toxoplasmic retinochoroiditis are discussed.

Wetting film stability and flotation kinetics.

Single bubble experiments performed with different size fractions of quartz particles and different, but known, contact angles revealed two modes of flotation dynamics in superclean water. (1.) A monotonic increase of collection efficiency Ecoll with increasing particle size was observed at high particle hydrophobicity and, correspondingly, a low wetting film stability (WFS). (2.) At low particle hydrophobicity and, correspondingly, high WFS, an extreme dependence of Ecoll on particle size was observed. The use of superclean water in our experiments prevented the retardation of bubble surface movement caused by surfactants or other impurities that is usual for other investigations and where particle-bubble inertial hydrodynamic interactions are suppressed. In the present study the free movement of the bubble surface enhances particle-bubble inertial interaction, creating conditions for different flotation modes, dependent on WFS. At the instant of inertial impact, a particle deforms the bubble surface, which may cause its rebound. Where the stability of the thin water film, formed between opposing surfaces of a bubble and a particle, is low, its rupture is accompanied with three phase contact line extension and contact angle formation before rebound. This prevents rebound, i.e. the first collision is accompanied by attachment. A high WFS prevents rupture during an impact. As a result, a contact angle does not arise and rebound is not prevented. However, rebound is accompanied by a second collision, the kinetic energy of which is smaller and can cause attachment at repetitive collision. These qualitative considerations are confirmed by the model quantification and comparison with measured Ecoll. For the first time the Sutherland equation (SE) for Ecoll is confirmed by experiment for smaller particle sizes and, correspondingly, very small Stokes numbers. The larger the particle size, the larger is the measured deviation from the SE. The SE is generalized, accounting for the centrifugal force, pressing hydrodynamic force and drainage in the low WFS case and, correspondingly, attachment occurs at first collision or during sliding. The derived generalized Sutherland equation (GSE) describes experimental data at low WFS. However, its application without account for possible rebound does not explain the measured extreme dependence in the case of high WFS. The theory for drainage during particle impact and the beginning of rebound enables conditions for either attachment or rebound in terms of the normal component of the impact velocity and the critical film thickness to be derived. Combining this condition with the GSE allowed the equation for Ecoll to be derived, accounting for attachment area shrinkage and attachment during a repetitive collision. This equation predicts the extreme dependence. Thus the WFS determines the modes of flotation dynamics and, in turn, probably affects the mechanisms, which control the flotation domain. At low WFS its upper boundary is controlled by the stability of the particle-bubble aggregate. At high WFS the upper boundary can be controlled by rebound because the latter reduces the attachment efficiency by a factor of 30 or more even with repetitive collision.

Electrokinetic properties of methylated quartz capillaries.

Electrokinetic (zeta)-potentials of methylated (trimethylchlorosilane) quartz capillaries (5-6 microm in radius) were determined in 10(-4) M KCl solution. Over the course of time, the absolute values of the zeta-potential decrease, as a result of the formation of small bubbles on the rough methylated surface, generated from the flowing, nitrogen gas-saturated solution. This decrease is attributed to screening of a part of the solid surface. After the passage of time, a sharp increase in the zeta-potentials was observed, as the pressure was increased and the initial potential values were recovered. Sometimes, oscillations in the zeta-potentials were observed. This behaviour was explained by detachment of bubbles from the methylated surfaces by the flowing solution. Addition of non-ionic surfactant, which made the methylated surface hydrophilic, decreased the measured zeta-potentials. This was attributed to suppression of water slippage, an effect known to occur for hydrophobic solid surfaces. A mixed mechanism of charge formation is characteristic for these methylated quartz surfaces and is connected with presence of hydrophobic and hydrophilic areas. The ratio between these areas controls both the formation of surface charge as well as the contact angles.