The envelope gene of transmitted HIV-1 resists a late interferon gamma-induced block

Type I interferon (IFN) signaling engenders an antiviral state that likely plays an important role in constraining HIV-1 transmission and contributes to defining subsequent AIDS pathogenesis. Type II IFN (IFNγ) also induces an antiviral state but is often primarily considered to be an immunomodulatory cytokine. We report that IFNγ stimulation can induce an antiviral state that can be both distinct from that of type I interferon, and can potently inhibit HIV-1 in primary CD4+ T cells and a number of human cell lines. Strikingly, we find that transmitted/founder (TF) HIV-1 viruses can resist a late block that is induced by type II IFN, and the use of chimeric IFNγ- sensitive/resistant viruses indicates that interferon-resistance maps to the env gene. Simultaneously, in vitro evolution also revealed that just a single amino acid substitution in envelope can confer substantial resistance to IFN-mediated inhibition. Thus, the env gene of transmitted HIV-1 confers resistance to a late block that is phenotypically distinct from those previously described to be resisted by env, and is therefore mediated by unknown IFNγ-stimulated factor(s) in human CD4+ T cells and cell lines. This important unidentified block could play a key role in constraining HIV-1 transmission

Wild snakes harbor West Nile virus

West Nile virus (WNV) has a complex eco-epidemiology with birds acting as reservoirs and hosts for the virus. Less well understood is the role of reptiles, especially in wild populations. The goal of our study was to determine whether a wild population of snakes in Pennsylvania harbored WNV. Six species of snakes were orally sampled in the summer of 2013 and were tested for the presence of WNV viral RNA using RT-PCR. Two Eastern Garter Snakes, Thamnophis sirtalis sirtalis tested positive for viral RNA (2/123, 1.62%). These results indicate a possible role for snakes in the complex transmission cycle of WNV

Lorentz invariance of effective strings

Starting from a Poincar\'e invariant field theory of a real scalar field with interactions governed by a double-well potential in 2+1 dimensions, the Lorentz representation induced on the collective coordinates describing low-energy excitations about an effective string background is derived. In this representation, Lorentz transformations are given in terms of an infinite series, in powers of derivatives along the worldsheet. Transformations that act on the direction transverse to the string worldsheet involve a universal dimension $-1$ term. As a consequence, Lorentz invariance holds in this theory of long effective strings due to cancellations in the action between irrelevant terms and the dimension two term that describes free massless scalar fields in two dimensions. (in plain tex, no macropackages necessary)Comment: 9 page

Trends in sexually transmitted infections in general practice 1990-2000: population based study using data from the UK general practice research database

Objective: To describe the contribution of primary care to the diagnosis and management of sexually transmitted infections in the United Kingdom, 1990-2000, in the context of increasing incidence of infections in genitourinary medicine clinics. Design: Population based study. Setting: UK primary care. Participants: Patients registered in the UK general practice research database. Main outcome measures: Incidence of diagnosed sexually transmitted infections in primary care and estimation of the proportion of major such infections diagnosed in primary care. Results: An estimated 23.0% of chlamydia cases in women but only 5.3% in men were diagnosed and treated in primary care during 1998-2000, along with 49.2% cases of non-specific urethritis and urethral discharge in men and 5.7% cases of gonorrhoea in women and 2.9% in men. Rates of diagnosis in primary care rose substantially in the late 1990s. Conclusions: A substantial and increasing number of sexually transmitted infections are diagnosed and treated in primary care in the United Kingdom, with sex ratios differing from those in genitourinary medicine clinics. Large numbers of men are treated in primary care for presumptive sexually transmitted infections

Allergic Contact Dermatitis and Autoeczematization to Proctosedyl® Cream and Proctomyxin® Cream

Proctosedyl® and Proctomyxin® are two commonly prescribed hemorrhoid therapies. Their topical application to the perianal region may be complicated by a local allergic contact dermatitis and subsequent autoeczematization reaction. We present three cases of an autoeczematization (ID) reaction to varying topical allergens found in Proctosedyl®/Proctomyxin®. It is our recommendation that physician and patient education, avoidance of allergens (or cross-reactants), and appropriate choice of topical corticosteroid is important in preventing and avoiding flares

Prioritized Detection of Personally Familiar Faces

We investigated whether personally familiar faces are preferentially processed in conditions of reduced attentional resources and in the absence of conscious awareness. In the first experiment, we used Rapid Serial Visual Presentation (RSVP) to test the susceptibility of familiar faces and faces of strangers to the attentional blink. In the second experiment, we used continuous flash interocular suppression to render stimuli invisible and measured face detection time for personally familiar faces as compared to faces of strangers. In both experiments we found an advantage for detection of personally familiar faces as compared to faces of strangers. Our data suggest that the identity of faces is processed with reduced attentional resources and even in the absence of awareness. Our results show that this facilitated processing of familiar faces cannot be attributed to detection of low-level visual features and that a learned unique configuration of facial features can influence preconscious perceptual processing

Motif Discovery through Predictive Modeling of Gene Regulation

We present MEDUSA, an integrative method for learning motif models of transcription factor binding sites by incorporating promoter sequence and gene expression data. We use a modern large-margin machine learning approach, based on boosting, to enable feature selection from the high-dimensional search space of candidate binding sequences while avoiding overfitting. At each iteration of the algorithm, MEDUSA builds a motif model whose presence in the promoter region of a gene, coupled with activity of a regulator in an experiment, is predictive of differential expression. In this way, we learn motifs that are functional and predictive of regulatory response rather than motifs that are simply overrepresented in promoter sequences. Moreover, MEDUSA produces a model of the transcriptional control logic that can predict the expression of any gene in the organism, given the sequence of the promoter region of the target gene and the expression state of a set of known or putative transcription factors and signaling molecules. Each motif model is either a $k$-length sequence, a dimer, or a PSSM that is built by agglomerative probabilistic clustering of sequences with similar boosting loss. By applying MEDUSA to a set of environmental stress response expression data in yeast, we learn motifs whose ability to predict differential expression of target genes outperforms motifs from the TRANSFAC dataset and from a previously published candidate set of PSSMs. We also show that MEDUSA retrieves many experimentally confirmed binding sites associated with environmental stress response from the literature.Comment: RECOMB 200

Rotational Cooling of Polar Molecules by Stark-tuned Cavity Resonance

A general scheme for rotational cooling of diatomic heteronuclear molecules is proposed. It uses a superconducting microwave cavity to enhance the spontaneous decay via Purcell effect. Rotational cooling can be induced by sequentially tuning each rotational transition to cavity resonance, starting from the highest transition level to the lowest using an electric field. Electrostatic multipoles can be used to provide large confinement volume with essentially homogeneous background electric field.Comment: 10 pages, 6 figure

The relationship between vertical leg stiffness and gross mechanical efficiency in cyclists

Background: Professional cyclists have been shown to have a mechanical efficiency that is 11% higher compared to amateur cyclists (Coyle et al. 1991: Med Sci Sports Exerc, 23 (1), 93-107). The variations in power between professional and amateur cyclists are associated with a greater torque development at the first phase of the pedal revolution (Coyle et al. 1991). It has also been shown in cyclists that a relationship exists between vertical leg stiffness and the peak power output (PPO) (r = 0.75, p < 0.01) achieved during a 30 s Wingate test (Pitchers et al. 2013: The relationship of vertical leg stiffness, peak power output and V̇O2max in recreationally active cyclists: identification of the interface between human and bike. 9th Annual Conference of the United Kingdom Strength & Conditioning Association, Nottingham, UK). Vertical leg stiffness may be important to cycling performance as the majority of the force produced is vertical and optimisation of the stretch shortening cycle may limit energy wastage during the propulsive phase (So et al. 2005: Phys Ther Sports, 6, 89-96; Fonda & Sarabon 2010: Sport Sci Rev, 19 (1), 187-210). The relationship between vertical leg stiffness and mechanical efficiency during cycling has yet to be examined. \ud Purpose: To assess the relationship between vertical leg stiffness and gross mechanical efficiency (GE) in cycling. \ud Methods: In a single group, within subjects design, 11 recreationally active male cyclists (age 34 ± 6 y, V̇O2max 57.4 ± 7.5 ml∙kg∙min-1, body mass 81 ± 1.2 kg, stature 1.81 ± 0.06 m) completed two testing sessions, with a minimum of 48 hr rest between each session. In the first testing session participants completed a stiffness familiarisation before an incremental cycle test to establish V̇O2max. At the second session participants completed 20 sub-maximal bilateral hops at a frequency of 2.3 Hz. This was followed by three 8 min sub-maximal cycling bouts at 50, 55 and 60 % of the participants’ individual maximal minute power (MMP) to establish GE (Table I). \ud Results: Mean values for GE and vertical leg stiffness were 19.0 ± 1.4 % and 34.1 ± 9.0 kN∙m-1, respectively. Pearson’s correlation coefficient revealed no relationship between vertical leg stiffness and GE (r = -0.07, p = 0.85). \ud Discussion: The main finding is that in recreationally active male cyclists there is no relationship between vertical leg stiffness and GE. In this group these findings indicate that GE is likely influenced more by other biological systems rather than the mechanical properties of the musculoskeletal system. However, these data may not be reflective of an elite sample where higher leg stiffness might be more likely to influence GE at higher power outputs.\ud Conclusion: Whilst vertical leg stiffness has been shown to have a strong relationship with PPO (Pitchers et al 2013) in recreational cyclists, this is not the case for GE. Further work is needed to establish if this is also the case in an elite population

Experimental feasibility of measuring the gravitational redshift of light using dispersion in optical fibers

This paper describes a new class of experiments that use dispersion in optical fibers to convert the gravitational frequency shift of light into a measurable phase shift or time delay. Two conceptual models are explored. In the first model, long counter-propagating pulses are used in a vertical fiber optic Sagnac interferometer. The second model uses optical solitons in vertically separated fiber optic storage rings. We discuss the feasibility of using such an instrument to make a high precision measurement of the gravitational frequency shift of light.Comment: 11 pages, 12 figure