Vector boson pair production at the LHC

We present phenomenological results for vector boson pair production at the LHC, obtained using the parton-level next-to-leading order program MCFM. We include the implementation of a new process in the code, pp -> \gamma\gamma, and important updates to existing processes. We incorporate fragmentation contributions in order to allow for the experimental isolation of photons in \gamma\gamma, W\gamma, and Z\gamma production and also account for gluon-gluon initial state contributions for all relevant processes. We present results for a variety of phenomenological scenarios, at the current operating energy of \sqrt{s} = 7 TeV and for the ultimate machine goal, \sqrt{s} = 14 TeV. We investigate the impact of our predictions on several important distributions that enter into searches for new physics at the LHC.Comment: 35 pages, 14 figure

High-resolution analysis of multi-copy variant surface glycoprotein gene expression sites in African trypanosomes

BACKGROUND: African trypanosomes cause lethal diseases in humans and animals and escape host immune attack by switching the expression of Variant Surface Glycoprotein (VSG) genes. The expressed VSGs are located at the ends of telomeric, polycistronic transcription units known as VSG expression sites (VSG-ESs). Each cell has many VSG-ESs but only one is transcribed in bloodstream-form parasites and all of them are inactive upon transmission to the insect vector mid-gut; a subset of monocistronic metacyclic VSG-ESs are then activated in the insect salivary gland. Deep-sequence analyses have been informative but assigning sequences to individual VSG-ESs has been challenging because they each contain closely related expression-site associated genes, or ESAGs, thought to contribute to virulence. RESULTS: We utilised ART, an in silico short read simulator to demonstrate the feasibility of accurately aligning reads to VSG-ESs. Then, using high-resolution transcriptomes from isogenic bloodstream and insect-stage Lister 427 Trypanosoma brucei, we uncover increased abundance in the insect mid-gut stage of mRNAs from metacyclic VSG-ESs and of mRNAs from the unusual ESAG, ESAG10. Further, we show that the silencing associated with allelic exclusion involves repression focussed at the ends of the VSG-ESs. We also use the approach to report relative fitness costs following ESAG RNAi from a genome-scale screen. CONCLUSIONS: By assigning sequences to individual VSG-ESs we provide new insights into VSG-ES transcription control, allelic exclusion and impacts on fitness. Thus, deeper insights into the expression and function of regulated multi-gene families are more accessible than previously anticipated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3154-8) contains supplementary material, which is available to authorized users

Locomotor Adaptation versus Perceptual Adaptation when Stepping Over an Obstacle with a Height Illusion

Background During locomotion, vision is used to perceive environmental obstacles that could potentially threaten stability; locomotor action is then modified to avoid these obstacles. Various factors such as lighting and texture can make these environmental obstacles appear larger or smaller than their actual size. It is unclear if gait is adapted based on the actual or perceived height of these environmental obstacles. The purposes of this study were to determine if visually guided action is scaled to visual perception, and to determine if task experience influenced how action is scaled to perception. Methodology/Principal Findings Participants judged the height of two obstacles before and after stepping over each of them 50 times. An illusion made obstacle one appear larger than obstacle two, even though they were identical in size. The influence of task experience was examined by comparing the perception-action relationship during the first five obstacle crossings (1–5) with the last five obstacle crossings (46–50). In the first set of trials, obstacle one was perceived to be 2.0 cm larger than obstacle two and subjects stepped 2.7 cm higher over obstacle one. After walking over the obstacle 50 times, the toe elevation was not different between obstacles, but obstacle one was still perceived as 2.4 cm larger. Conclusions/Significance There was evidence of locomotor adaptation, but no evidence of perceptual adaptation with experience. These findings add to research that demonstrates that while the motor system can be influenced by perception, it can also operate independent of perception

Identification and functional characterisation of CRK12:CYC9, a novel cyclin-dependent kinase (CDK)-cyclin complex in Trypanosoma brucei

The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs) and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo. Here we report the identification of a previously uncharacterised CRK:cyclin complex between CRK12 and the putative transcriptional cyclin, CYC9. CRK12:CYC9 interact to form an active protein kinase complex in procyclic and bloodstream T. brucei. Both CRK12 and CYC9 are essential for the proliferation of bloodstream trypanosomes in vitro, and we show that CRK12 is also essential for survival of T. brucei in a mouse model, providing genetic validation of CRK12:CYC9 as a novel drug target for trypanosomiasis. Further, functional characterisation of CRK12 and CYC9 using RNA interference reveals roles for these proteins in endocytosis and cytokinesis, respectively

Influence of dental metallic artifact from multislice CT in the assessment of simulated mandibular lesions

OBJECTIVE: This study evaluated the influence of metallic dental artifacts on the accuracy of simulated mandibular lesion detection by using multislice technology. MATERIAL AND METHODS: Fifteen macerated mandibles were used. Perforations were done simulating bone lesions and the mandibles were subjected to axial 16 rows multislice CT images using 0.5 mm of slice thickness with 0.3 mm interval of reconstruction. Metallic dental restorations were done and the mandibles were subjected again to CT in the same protocol. The images were analyzed to detect simulated lesions in the mandibles, verifying the loci number and if there was any cortical perforation exposing medullar bone. The analysis was performed by two independent examiners using e-film software. RESULTS: The samples without artifacts presented better results compared to the gold standard (dried mandible with perforations). In the samples without artifacts, all cortical perforation were identified and 46 loci were detected (of 51) in loci number analysis. Among the samples with artifacts, 12 lesions out of 14 were recognized regarding medullar invasion, and 40 out of 51 concerning loci number. The sensitivity in samples without artifacts was 90% and 100% regarding loci number and medullar invasion, respectively. In samples with artifacts, these values dropped to 78% and 86%, respectively. The presence of metallic restorations affected the sensitivity values of the method, but the difference was not significant (p>0.05). CONCLUSIONS: Although there were differences in the results of samples with and without artifacts, the presence of metallic restoration did not lead to misinterpretation of the final diagnosis. However, the validity of multislice CT imaging in this study was established for detection of simulated mandibular bone lesions.CNPqFAPESPCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

Haiku - a Scala combinator toolkit for semi-automated composition of metaheuristics

There is an emerging trend towards the automated design of metaheuristics at the software component level. In principle, metaheuristics have a relatively clean decomposition, where well-known frameworks such as ILS and EA are parametrised by variant components for acceptance, perturbation etc. Automated generation of these frameworks is not so simple in practice, since the coupling between components may be implementation specific. Compositionality is the ability to freely express a space of designs ‘bottom up’ in terms of elementary components: previous work in this area has used combinators, a modular and functional approach to componentisation arising from foundational Computer Science. In this article, we describeHaiku, a combinator tool-kit written in the Scala language, which builds upon previous work to further automate the process by automatically composing the external dependencies of components. We provide examples of use and give a case study in which a programatically-generated heuristic is applied to the Travelling Salesman Problem within an Evolutionary Strategies framework