2,220 research outputs found
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 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
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
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
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 -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
Research-informed design, management and maintenance of infrastructure slopes: development of a multi-scalar approach
The UK’s transport infrastructure is one of the most heavily used in the world. The performance of these networks is critically dependent on the performance of cutting and embankment slopes which make up £20B of the £60B asset value of major highway infrastructure alone. The rail network in particular is also one of the oldest in the world: many of these slopes are suffering high incidents of instability (increasing with time). This paper describes the development of a fundamental understanding of earthwork material and system behaviour, through the systematic integration of research across a range of spatial and temporal scales. Spatially these range from microscopic studies of soil fabric, through elemental materials behaviour to whole slope modelling and monitoring and scaling up to transport networks. Temporally, historical and current weather event sequences are being used to understand and model soil deterioration processes, and climate change scenarios to examine their potential effects on slope performance in futures up to and including the 2080s. The outputs of this research are being mapped onto the different spatial and temporal scales of infrastructure slope asset management to inform the design of new slopes through to changing the way in which investment is made into aging assets. The aim ultimately is to help create a more reliable, cost effective, safer and more resilient transport system
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