Electrostatic Repulsion of Positively Charged Vesicles and Negatively Charged Objects

A positively charged, mixed bilayer vesicle in the presence of negatively charged surfaces (for example, colloidal particles) can spontaneously partition into an adhesion zone of definite area, and another zone that repels additional negative objects. Although the membrane itself has nonnegative charge in the repulsive zone, negative counterions on the interior of the vesicle spontaneously aggregate there, and present a net negative charge to the exterior. Beyond the fundamental result that oppositely charged objects can repel, our mechanism helps explain recent experiments on surfactant vesicles.Comment: Latex using epsfig and afterpage; pdf available at http://www.physics.upenn.edu/~nelson/Mss/repel.pd

Missense-depleted regions in population exomes implicate ras superfamily nucleotide-binding protein alteration in patients with brain malformation.

Genomic sequence interpretation can miss clinically relevant missense variants for several reasons. Rare missense variants are numerous in the exome and difficult to prioritise. Affected genes may also not have existing disease association. To improve variant prioritisation, we leverage population exome data to identify intragenic missense-depleted regions (MDRs) genome-wide that may be important in disease. We then use missense depletion analyses to help prioritise undiagnosed disease exome variants. We demonstrate application of this strategy to identify a novel gene association for human brain malformation. We identified de novo missense variants that affect the GDP/GTP-binding site of ARF1 in three unrelated patients. Corresponding functional analysis suggests ARF1 GDP/GTP-activation is affected by the specific missense mutations associated with heterotopia. These findings expand the genetic pathway underpinning neurologic disease that classically includes FLNA. ARF1 along with ARFGEF2 add further evidence implicating ARF/GEFs in the brain. Using functional ontology, top MDR-containing genes were highly enriched for nucleotide-binding function, suggesting these may be candidates for human disease. Routine consideration of MDR in the interpretation of exome data for rare diseases may help identify strong genetic factors for many severe conditions, infertility/reduction in reproductive capability, and embryonic conditions contributing to preterm loss

Shear behaviour of lightweight concrete beams strengthened with CFRP composite

This paper presents the experimental results obtained from lightweight and normal concrete beams with closed and U-shaped configurations of epoxy bonded Carbon FRP (CFRP) reinforcement in order to compare the shear resisting mechanisms between lightweight and normal concrete beams. The experimental results show that the CFRP can successfully be applied in the strengthening of lightweight concrete beams and the shear strength gained due to CFRP reinforcement for lightweight samples is less than the normal weight concrete samples while the mode of failures are the same. In contrast, diagonal shear cracks propagate through the lightweight aggregate compared to cracks around normal aggregate in the concrete matrix. Furthermore, the numerical study shows that the design guidelines to estimate the CFRP contribution, which do not differentiate the concrete types, overestimate the U-shaped CFRP contribution on lightweight concrete beams where the effective bond length of CFRP could not be achieved due to lower tensile strength of lightweight concrete

Improved Resolution of Reef-Coral Endosymbiont (Symbiodinium) Species Diversity, Ecology, and Evolution through psbA Non-Coding Region Genotyping

Ribosomal DNA sequence data abounds from numerous studies on the dinoflagellate endosymbionts of corals, and yet the multi-copy nature and intragenomic variability of rRNA genes and spacers confound interpretations of symbiont diversity and ecology. Making consistent sense of extensive sequence variation in a meaningful ecological and evolutionary context would benefit from the application of additional genetic markers. Sequences of the non-coding region of the plastid psbA minicircle (psbAncr) were used to independently examine symbiont genotypic and species diversity found within and between colonies of Hawaiian reef corals in the genus Montipora. A single psbAncr haplotype was recovered in most samples through direct sequencing (∼80–90%) and members of the same internal transcribed spacer region 2 (ITS2) type were phylogenetically differentiated from other ITS2 types by substantial psbAncr sequence divergence. The repeated sequencing of bacterially-cloned fragments of psbAncr from samples and clonal cultures often recovered a single numerically common haplotype accompanied by rare, highly-similar, sequence variants. When sequence artifacts of cloning and intragenomic variation are factored out, these data indicate that most colonies harbored one dominant Symbiodinium genotype. The cloning and sequencing of ITS2 DNA amplified from these same samples recovered numerically abundant variants (that are diagnostic of distinct Symbiodinium lineages), but also generated a large amount of sequences comprising PCR/cloning artifacts combined with ancestral and/or rare variants that, if incorporated into phylogenetic reconstructions, confound how small sequence differences are interpreted. Finally, psbAncr sequence data from a broad sampling of Symbiodinium diversity obtained from various corals throughout the Indo-Pacific were concordant with ITS lineage membership (defined by denaturing gradient gel electrophoresis screening), yet exhibited substantially greater sequence divergence and revealed strong phylogeographic structure corresponding to major biogeographic provinces. The detailed genetic resolution provided by psbAncr data brings further clarity to the ecology, evolution, and systematics of symbiotic dinoflagellates

Intrinsic ripples in graphene

The stability of two-dimensional (2D) layers and membranes is subject of a long standing theoretical debate. According to the so called Mermin-Wagner theorem, long wavelength fluctuations destroy the long-range order for 2D crystals. Similarly, 2D membranes embedded in a 3D space have a tendency to be crumpled. These dangerous fluctuations can, however, be suppressed by anharmonic coupling between bending and stretching modes making that a two-dimensional membrane can exist but should present strong height fluctuations. The discovery of graphene, the first truly 2D crystal and the recent experimental observation of ripples in freely hanging graphene makes these issues especially important. Beside the academic interest, understanding the mechanisms of stability of graphene is crucial for understanding electronic transport in this material that is attracting so much interest for its unusual Dirac spectrum and electronic properties. Here we address the nature of these height fluctuations by means of straightforward atomistic Monte Carlo simulations based on a very accurate many-body interatomic potential for carbon. We find that ripples spontaneously appear due to thermal fluctuations with a size distribution peaked around 70 \AA which is compatible with experimental findings (50-100 \AA) but not with the current understanding of stability of flexible membranes. This unexpected result seems to be due to the multiplicity of chemical bonding in carbon.Comment: 14 pages, 6 figure

Divergent mathematical treatments in utility theory

In this paper I study how divergent mathematical treatments affect mathematical modelling, with a special focus on utility theory. In particular I examine recent work on the ranking of information states and the discounting of future utilities, in order to show how, by replacing the standard analytical treatment of the models involved with one based on the framework of Nonstandard Analysis, diametrically opposite results are obtained. In both cases, the choice between the standard and nonstandard treatment amounts to a selection of set-theoretical parameters that cannot be made on purely empirical grounds. The analysis of this phenomenon gives rise to a simple logical account of the relativity of impossibility theorems in economic theory, which concludes the paper

HCV reinfection incidence and spontaneous clearance rates in HIV-positive men who have sex with men in Western Europe

BACKGROUND & AIMS: Moderate cure rates of acute hepatitis C virus (HCV) infections with pegylated interferon and ribavirin have been described in the last decade in men who have sex with men (MSM), who are also coinfected with the human immunodeficiency virus (HIV). However, a subsequent high incidence of HCV reinfections has been reported regionally in men who both clear the infection spontaneously or who respond to treatment. METHODS: Retrospective analysis of reinfections in HIV infected MSM in eight centers from Austria, France, Germany, and the UK within the NEAT network between May 2002 and June 2014. RESULTS: Of 606 individuals who cleared HCV spontaneously or were successfully treated, 149 (24.6%) presented with a subsequent HCV reinfection. Thirty out of 70 (43%) who cleared again or were successfully treated, presented with a second reinfection, 5 with a third, and one with a fourth reinfection. The reinfection incidence was 7.3/100 person-years (95% CI 6.2-8.6). We found a trend for lower incidence among individuals who had spontaneously cleared their incident infection than among individuals who were treated (Hazard ratio 0.62, 95% CI 0.38-1.02, p=0.06). Spontaneous clearance of reinfection was associated with ALT levels >1000IU/ml and spontaneous clearance of a prior infection. CONCLUSIONS: HCV reinfection is an issue of major concern in HIV-positive MSM. Prevention strategies are needed for high risk groups to reduce morbidity and treatment costs. HIV-positive MSM with a prior HCV infection should be tested every 3 to 6months for reinfection. Those who had achieved a reinfection should be tested every 3months. LAY SUMMARY: We evaluated the occurrence of HCV reinfection in HIV-positive men who have sex with men. We found an alarming incidence of 7.3/100 person-years. Prevention measures need to address this specific subgroup of patients at high risk for HCV

Eosinophil and T Cell Markers Predict Functional Decline in COPD Patients

BACKGROUND. The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1). However, asingle measurement of FEV1 cannot reliably predict subsequent decline. Recent studies indicate that T lymphocytes and eosinophils are important determinants of disease stability in COPD. We therefore measured cytokine levels in the lung lavage fluid and plasma of COPD patients in order to determine if the levels of T cell or eosinophil related cytokines were predictive of the future course of the disease. METHODS. Baseline lung lavage and plasma samples were collected from COPD subjects with moderately severe airway obstruction and emphysematous changes on chest CT. The study participants were former smokers who had not had a disease exacerbation within the past six months or used steroids within the past two months. Those subjects who demonstrated stable disease over the following six months (ΔFEV1 % predicted = 4.7 ± 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (ΔFEV1 % predicted = -16.0 ± 6.0; N = 16) during the same time period and with normal controls (N = 11). Plasma and lung lavage cytokines were measured from clinical samples using the Luminex multiplex kit which enabled the simultaneous measurement of several T cell and eosinophil related cytokines. RESULTS AND DISCUSSION. Stable COPD participants had significantly higher plasma IL-2 levels compared to participants with rapidly progressive COPD (p = 0.04). In contrast, plasma eotaxin-1 levels were significantly lower in stable COPD subjects compared to normal controls (p < 0.03). In addition, lung lavage eotaxin-1 levels were significantly higher in rapidly progressive COPD participants compared to both normal controls (p < 0.02) and stable COPD participants (p < 0.05). CONCLUSION. These findings indicate that IL-2 and eotaxin-1 levels may be important markers of disease stability in advanced emphysema patients. Prospective studies will need to confirm whether measuring IL-2 or eotaxin-1 can identify patients at risk for rapid disease progression.National Heart, Lung, and Blood Institute (NO1-HR-96140, NO1-HR-96141-001, NO1-HR-96144, NO1-HR-96143; NO1-HR-96145; NO1-HR-96142, R01HL086936-03); The Flight Attendant Medical Research Institute; the Jo-Ann F. LeBuhn Center for Chest Diseas