Low-Energy Theorems from Holography

In the context of gauge/gravity duality, we verify two types of gauge theory low-energy theorems, the dilation Ward identities and the decoupling of heavy flavor. First, we provide an analytic proof of non-trivial dilation Ward identities for a theory holographically dual to a background with gluon condensate (the self-dual Liu--Tseytlin background). In this way an important class of low-energy theorems for correlators of different operators with the trace of the energy-momentum tensor is established, which so far has been studied in field theory only. Another low-energy relationship, the so-called decoupling theorem, is numerically shown to hold universally in three holographic models involving both the quark and the gluon condensate. We show this by comparing the ratio of the quark and gluon condensates in three different examples of gravity backgrounds with non-trivial dilaton flow. As a by-product of our study, we also obtain gauge field condensate contributions to meson transport coefficients.Comment: 32 pages, 4 figures, two references added, typos remove

Automatically extracting functionally equivalent proteins from SwissProt

In summary, FOSTA provides an automated analysis of annotations in UniProtKB/Swiss-Prot to enable groups of proteins already annotated as functionally equivalent, to be extracted. Our results demonstrate that the vast majority of UniProtKB/Swiss-Prot functional annotations are of high quality, and that FOSTA can interpret annotations successfully. Where FOSTA is not successful, we are able to highlight inconsistencies in UniProtKB/Swiss-Prot annotation. Most of these would have presented equal difficulties for manual interpretation of annotations. We discuss limitations and possible future extensions to FOSTA, and recommend changes to the UniProtKB/Swiss-Prot format, which would facilitate text-mining of UniProtKB/Swiss-Prot

Conditional statistics of electron transport in interacting nanoscale conductors

Interactions between nanoscale semiconductor structures form the basis for charge detectors in the solid state. Recent experimental advances have demonstrated the on-chip detection of single electron transport through a quantum dot (QD). The discreteness of charge in units of e leads to intrinsic fluctuations in the electrical current, known as shot noise. To measure these single-electron fluctuations a nearby coherent conductor, called a quantum point contact (QPC), interacts with the QD and acts as a detector. An important property of the QPC charge detector is noninvasiveness: the system physically affects the detector, not visa-versa. Here we predict that even for ideal noninvasive detectors such as the QPC, when a particular detector result is observed, the system suffers an informational backaction, radically altering the statistics of transport through the QD as compared to the unconditional shot noise. We develop a theoretical model to make predictions about the joint current probability distributions and conditional transport statistics. The experimental findings reported here demonstrate the reality of informational backaction in nanoscale systems as well as a variety of new effects, such as conditional noise enhancement, which are in essentially perfect agreement with our model calculations. This type of switching telegraph process occurs abundantly in nature, indicating that these results are applicable to a wide variety of systems.Comment: 16 pages, 3 figures, to appear in Nature Physic

A Review of 2011 for PLoS Computational Biology

A Review of 2011 for <em>PLoS Computational Biology</em

Physicochemical analysis of rotavirus segment 11 supports a 'modified panhandle' structure and not the predicted alternative tRNA-like structure (TRLS)

.Rotaviruses are a major cause of acute gastroenteritis, which is often fatal in infants. The viral genome consists of 11 double-stranded RNA segments, but little is known about their cis-acting sequences and structural elements. Covariation studies and phylogenetic analysis exploring the potential structure of RNA11 of rotaviruses suggested that, besides the previously predicted "modified panhandle" structure, the 5' and 3' termini of one of the isoforms of the bovine rotavirus UKtc strain may interact to form a tRNA-like structure (TRLS). Such TRLSs have been identified in RNAs of plant viruses, where they are important for enhancing replication and packaging. However, using tRNA mimicry assays (in vitro aminoacylation and 3'- adenylation), we found no biochemical evidence for tRNA-like functions of RNA11. Capping, synthetic 3' adenylation and manipulation of divalent cation concentrations did not change this finding. NMR studies on a 5'- and 3'-deletion construct of RNA11 containing the putative intra-strand complementary sequences supported a predominant panhandle structure and did not conform to a cloverleaf fold despite the strong evidence for a predicted structure in this conserved region of the viral RNA. Additional viral or cellular factors may be needed to stabilise it into a form with tRNA-like properties

Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance.

BACKGROUND: Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance. METHODS: To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs. In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods. RESULTS: The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA-promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability. Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites. CONCLUSIONS: Using the TDR resource, we demonstrate the usefulness of whole genome association and convergent evolution approaches to detect known and potentially novel mutations associated with drug resistance. Further, protein structural modelling could provide a means of predicting the impact of polymorphisms on drug efficacy in the absence of phenotypic data. These approaches could ultimately lead to novel resistance mutations to improve the design of tuberculosis control measures, such as diagnostics, and inform patient management

Primary health care services for the aged in the United Arab Emirates: a comparison of two models of care

Aim: To compare the quality of aged care provided by two different models of primary health care services in the United Arab Emirates. Methods: Cross sectional survey by chart review of 200 consecutive people aged 65 years and over attending two primary health care centers located in adjacent suburbs and serving populations with similar characteristics; a resource intensive center (RIC) and the other a resource thrifty center (RTC). Quality indicators were blood pressure levels in hypertensives and glycosylated hemoglobin (HbA1c) levels in diabetics. Results: There was no variation in age, sex or number of visits per year between the clinics. Osteoarthritis, hypertension, and diabetes were the most common diagnoses at both. The people attending the RIC had a substantially higher level of comorbidity (RIC=1.19±1.18, RTC=0.63 ± 0.68, p < 0.001), the average systolic and diastolic blood pressure for those diagnosed with hypertension was in the normal range at the RIC (138.5 ± 19.8/77.1 ± 9.9), whereas it was significantly higher and in the elevated range at the RTC (149.5 ± 17.7/85.2 ± 9.1, p < 0.001) and the HbA1c was significantly lower at the RIC (7.7 ± 1.4) than at the RTC (9.5 ± 2.0, p < 0.001). Conclusions:The quality of health outcomes for the two chronic diseases, hypertension and diabetes, appeared significantly higher at the RIC, when compared with the RTC. However, there may have been significant selection bias. Further studies are needed to determine if the RIC improves quality measures in other aspects of chronic disease care and provides a more cost effective health care service

Pneumococcal carriage in sub-Saharan Africa--a systematic review.

BACKGROUND: Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. METHODS: A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. RESULTS: Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6-70.8) in children less than 5 years, 42.6% (95% CI: 29.9-55.4) in children 5-15 years and 28.0% (95% CI: 19.0-37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9-24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. CONCLUSION: Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination

A note on the propagation of quantized vortex rings through a quantum turbulence tangle:energy transport or energy dissipation?

We investigate quantum vortex ring dynamics at scales smaller than the inter-vortex spacing in quantum turbulence. Through geometrical arguments and high-resolution numerical simulations, we examine the validity of simple estimates for the mean free path and the structure of vortex rings post-reconnection. We find that a large proportion of vortex rings remain coherent objects where approximately 75% of their energy is preserved. This leads us to consider the effectiveness of energy transport in turbulent tangles. Moreover, we show that in low density tangles, appropriate for the ultra-quantum regime, ring emission cannot be ruled out as an important mechanism for energy dissipation. However at higher vortex line densities, typically associated with the quasi-classical regime, loop emission is expected to make a negligible contribution to energy dissipation, even allowing for the fact that our work shows rings can survive multiple reconnection events. Hence the Kelvin wave cascade seems the most plausible mechanism leading to energy dissipatio

Annexin A2 antibodies but not inhibitors of the annexin A2 heterotetramer impair productive HIV-1 infection of macrophages in vitro

During sexual transmission of human immunodeficiency virus (HIV), macrophages are initial targets for HIV infection. Secretory leukocyte protease inhibitor (SLPI) has been shown to protect against HIV infection of macrophages through interactions with annexin A2 (A2), which is found on the macrophage cell surface as a heterotetramer (A2t) consisting of A2 and S100A10. Therefore, we investigated potential protein-protein interactions between A2 and HIV-1 gp120 through a series of co-immunoprecipitation assays and a single molecule pulldown (SiMPull) technique. Additionally, inhibitors of A2t (A2ti) that target the interaction between A2 and S100A10 were tested for their ability to impair productive HIV-1 infection of macrophages. Our data suggest that interactions between HIV-1 gp120 and A2 exist, though this interaction may be indirect. Furthermore, an anti-A2 antibody impaired HIV-1 particle production in macrophages in vitro, whereas A2ti did not indicating that annexin A2 may promote HIV-1 infection of macrophages in its monomeric rather than tetrameric form