Parton distributions

I discuss our current understanding of parton distributions. I begin with the underlying theoretical framework, and the way in which different data sets constrain different partons, highlighting recent developments. The methods of examining the uncertainties on the distributions and those physical quantities dependent on them is analyzed. Finally I look at the evidence that additional theoretical corrections beyond NLO perturbative QCD may be necessary, what type of corrections are indicated and the impact these may have on the uncertainties.</jats:p

Outcomes of total hip arthroplasty, as a salvage procedure, following failed internal fixation of intracapsular fractures of the femoral neck: a systematic review and meta-analysis.

AIMS: The optimal management of intracapsular fractures of the femoral neck in independently mobile patients remains open to debate. Successful fixation obviates the limitations of arthroplasty for this group of patients. However, with fixation failure rates as high as 30%, the outcome of revision surgery to salvage total hip arthroplasty (THA) must be considered. We carried out a systematic review to compare the outcomes of salvage THA and primary THA for intracapsular fractures of the femoral neck. PATIENTS AND METHODS: We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) compliant systematic review, using the PubMed, EMBASE and Cochrane libraries databases. A meta-analysis was performed where possible, and a narrative synthesis when a meta-analysis was not possible. RESULTS: Our analyses revealed a significantly increased risk of complications including deep infection, early dislocation and peri-prosthetic fracture with salvage THA when compared with primary THA for an intracapsular fracture of the femoral neck (overall risk ratio of 3.15). Functional outcomes assessment using EuroQoL (EQ)-5D were not significantly different (p = 0.3). CONCLUSION: Salvage THA carries a significantly higher risk of complications than primary THA for intracapsular fractured neck of femur. Current literature is still lacking well designed studies to provide a full answer to the question. TAKE HOME MESSAGE: Salvage THA is associated with more complications than primary THA for intracapsular neck of femur fractures

Concurrent adaptation to opposing visual displacements during an alternating movement.

It has been suggested that, during tasks in which subjects are exposed to a visual rotation of cursor feedback, alternating bimanual adaptation to opposing rotations is as rapid as unimanual adaptation to a single rotation (Bock et al. in Exp Brain Res 162:513–519, 2005). However, that experiment did not test strict alternation of the limbs but short alternate blocks of trials. We have therefore tested adaptation under alternate left/right hand movement with opposing rotations. It was clear that the left and right hand, within the alternating conditions, learnt to adapt to the opposing displacements at a similar rate suggesting that two adaptive states were formed concurrently. We suggest that the separate limbs are used as contextual cues to switch between the relevant adaptive states. However, we found that during online correction the alternating conditions had a significantly slower rate of adaptation in comparison to the unimanual conditions. Control conditions indicate that the results are not directly due the alternation between limbs or to the constant switching of vision between the two eyes. The negative interference may originate from the requirement to dissociate the visual information of these two alternating displacements to allow online control of the two arms

APOBEC mutagenesis in drug resistance and immune escape in HIV and cancer evolution

The APOBEC mutational signature has only recently been detected in a multitude of cancers through next-generation sequencing. In contrast, APOBEC has been a focus of virology research for over a decade. Many lessons learnt regarding APOBEC within virology are likely to be applicable to cancer. In this review, we explore the parallels between the role of APOBEC enzymes in HIV and cancer evolution. We discuss data supporting the role of APOBEC mutagenesis in creating HIV genome heterogeneity, drug resistance, and immune escape variants. We hypothesize similar functions of APOBEC will also hold true in cancer

Interplay between pleiotropy and secondary selection determines rise and fall of mutators in stress response

Dramatic rise of mutators has been found to accompany adaptation of bacteria in response to many kinds of stress. Two views on the evolutionary origin of this phenomenon emerged: the pleiotropic hypothesis positing that it is a byproduct of environmental stress or other specific stress response mechanisms and the second order selection which states that mutators hitchhike to fixation with unrelated beneficial alleles. Conventional population genetics models could not fully resolve this controversy because they are based on certain assumptions about fitness landscape. Here we address this problem using a microscopic multiscale model, which couples physically realistic molecular descriptions of proteins and their interactions with population genetics of carrier organisms without assuming any a priori fitness landscape. We found that both pleiotropy and second order selection play a crucial role at different stages of adaptation: the supply of mutators is provided through destabilization of error correction complexes or fluctuations of production levels of prototypic mismatch repair proteins (pleiotropic effects), while rise and fixation of mutators occur when there is a sufficient supply of beneficial mutations in replication-controlling genes. This general mechanism assures a robust and reliable adaptation of organisms to unforeseen challenges. This study highlights physical principles underlying physical biological mechanisms of stress response and adaptation

Evaluating the potential for the environmentally sustainable control of foot and mouth disease in Sub-Saharan Africa

Strategies to control transboundary diseases have in the past generated unintended negative consequences for both the environment and local human populations. Integrating perspectives from across disciplines, including livestock, veterinary and conservation sectors, is necessary for identifying disease control strategies that optimise environmental goods and services at the wildlife-livestock interface. Prompted by the recent development of a global strategy for the control and elimination of foot-and-mouth disease (FMD), this paper seeks insight into the consequences of, and rational options for potential FMD control measures in relation to environmental, conservation and human poverty considerations in Africa. We suggest a more environmentally nuanced process of FMD control that safe-guards the integrity of wild populations and the ecosystem dynamics on which human livelihoods depend while simultaneously improving socio-economic conditions of rural people. In particular, we outline five major issues that need to be considered: 1) improved understanding of the different FMD viral strains and how they circulate between domestic and wildlife populations; 2) an appreciation for the economic value of wildlife for many African countries whose presence might preclude the country from ever achieving an FMD-free status; 3) exploring ways in which livestock production can be improved without compromising wildlife such as implementing commodity-based trading schemes; 4) introducing a participatory approach involving local farmers and the national veterinary services in the control of FMD; and 5) finally the possibility that transfrontier conservation might offer new hope of integrating decision-making at the wildlife-livestock interface

Recombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule.

Streptococcus pneumoniae causes a high burden of invasive pneumococcal disease (IPD) globally, especially in children from resource-poor settings. Like many bacteria, the pneumococcus can import DNA from other strains or even species by transformation and homologous recombination, which has allowed the pneumococcus to evade clinical interventions such as antibiotics and pneumococcal conjugate vaccines (PCVs). Pneumococci are enclosed in a complex polysaccharide capsule that determines the serotype; the capsule varies in size and is associated with properties including carriage prevalence and virulence. We determined and quantified the association between capsule and recombination events using genomic data from a diverse collection of serotypes sampled in Malawi. We determined both the amount of variation introduced by recombination relative to mutation (the relative rate) and how many individual recombination events occur per isolate (the frequency). Using univariate analyses, we found an association between both recombination measures and multiple factors associated with the capsule, including duration and prevalence of carriage. Because many capsular factors are correlated, we used multivariate analysis to correct for collinearity. Capsule size and carriage duration remained positively associated with recombination, although with a reduced P value, and this effect may be mediated through some unassayed additional property associated with larger capsules. This work describes an important impact of serotype on recombination that has been previously overlooked. While the details of how this effect is achieved remain to be determined, it may have important consequences for the serotype-specific response to vaccines and other interventions. IMPORTANCE: The capsule determines >90 different pneumococcal serotypes, which vary in capsule size, virulence, duration, and prevalence of carriage. Current serotype-specific vaccines elicit anticapsule antibodies. Pneumococcus can take up exogenous DNA by transformation and insert it into its chromosome by homologous recombination. This mechanism has disseminated drug resistance and generated vaccine escape variants. It is hence crucial to pneumococcal evolutionary response to interventions, but there has been no systematic study quantifying whether serotypes vary in recombination and whether this is associated with serotype-specific properties such as capsule size or carriage duration. Larger capsules could physically inhibit DNA uptake, or given the longer carriage duration for larger capsules, this may promote recombination. We find that recombination varies among capsules and is associated with capsule size, carriage duration, and carriage prevalence and negatively associated with invasiveness. The consequence of this work is that serotypes with different capsules may respond differently to selective pressures like vaccines

Interactions in vivo between the Vif protein of HIV-1 and the precursor (Pr55GAG) of the virion nucleocapsid proteins

The abnormality of viral core structure seen in vif-defective HIV-1 grown in PBMCs has suggested a role for Vif in viral morphogenesis. Using an in vivo mammalian two-hybrid assay, the interaction between Vif and the precursor (Pr55GAG) of the virion nucleocapsid proteins has been analysed. This revealed the amino-terminal (aa 1–22) and central (aa 70–100) regions of Vif to be essential for its interaction with Pr55GAG, but deletion of the carboxy-terminal (aa 158–192) region of the protein had only a minor effect on its interaction. Initial deletion studies carried out on Pr55GAG showed that a 35-amino-acid region of the protein bridging the MA(p17)–CA(p24) junction was essential for its ability to interact with Vif. Site-directed mutagenesis of a conserved tryptophan (Trp21) near the amino terminus of Vif showed it to be important for the interaction with Pr55GAG. By contrast, mutagenesis of the highly conserved YLAL residues forming part of the BC-box motif, shown to be important in Vif promoting degradation of APOBEC3G/3F, had little or no effect on the Vif–Pr55GAG interaction

Color & Weak triplet scalars, the dimuon asymmetry in BsB_s decay, the top forward-backward asymmetry, and the CDF dijet excess

The new physics required to explain the anomalies recently reported by the D0 and CDF collaborations, namely the top forward-backward asymmetry (FBA), the like-sign dimuon charge asymmetry in semileptonic b decay, and the CDF dijet excess, has to feature an amount of flavor symmetry in order to satisfy the severe constrains arising from flavor violation. In this paper we show that, once baryon number conservation is imposed, color & weak triplet scalars with hypercharge $Y=1/3$ can feature the required flavor structure as a consequence of standard model gauge invariance. The color & weak triplet model can simultaneously explain the top FBA and the dimuon charge asymmetry or the dimuon charge asymmetry and the CDF dijet excess. However, the CDF dijet excess appears to be incompatible with the top FBA in the minimal framework. Our model for the dimuon asymmetry predicts the observed pattern $h_d\ll h_s$ in the region of parameter space required to explain the top FBA, whereas our model for the CDF dijet anomaly is characterized by the absence of beyond the SM b-quark jets in the excess region. Compatibility of the color & weak triplet with the electroweak constraints is also discussed. We show that a Higgs boson mass exceeding the LEP bound is typically favored in this scenario, and that both Higgs production and decay can be significantly altered by the triplet. The most promising collider signature is found if the splitting among the components of the triplet is of weak scale magnitude.Comment: references added, published versio