Dominantly acting ABCC8 mutations in patients with medically unresponsive hyperinsulinaemic hypoglycaemia

Flanagan SE, Kapoor RR, Banerjee I, Hall C, Smith VV, Hussain K, Ellard S. Dominantly acting ABCC8 mutations in patients with medically unresponsive hyperinsulinaemic hypoglycaemia

Stringy effects in black hole decay

We compute the low energy decay rates of near-extremal three(four) charge black holes in five(four) dimensional N=4 string theory to sub-leading order in the large charge approximation. This involves studying stringy corrections to scattering amplitudes of a scalar field off a black hole. We adapt and use recently developed techniques to compute such amplitudes as near-horizon quantities. We then compare this with the corresponding calculation in the microscopic configuration carrying the same charges as the black hole. We find perfect agreement between the microscopic and macroscopic calculations; in the cases we study, the zero energy limit of the scattering cross section is equal to four times the Wald entropy of the black hole.Comment: 32 page

Benzyne in V4334 Sqr: A Quest for the Ring with SOFIA/EXES

Large aromatic molecules are ubiquitous in both circumstellar and interstellar environments. Detection of small aromatic molecules, such as benzene (C6H6) and benzyne (C6H4), are rare in astrophysical environments. Detection of such species will have major implications for our understanding of the astrochemistry involved in the formation of the molecules necessary for life, including modeling the chemical pathways to the formation of larger hydrocarbon molecules. We conducted a search for the infrared 18 μm spectral signature of benzyne in V4334 Sgr with the Stratospheric Observatory for Infrared Astronomy (SOFIA)/Echelon-Cross-Echelle Spectrograph (EXES) finding no evidence for a feature at the sensitivity of our observations

The Weak Gravity Conjecture and the Viscosity Bound with Six-Derivative Corrections

The weak gravity conjecture and the shear viscosity to entropy density bound place constraints on low energy effective field theories that may help to distinguish which theories can be UV completed. Recently, there have been suggestions of a possible correlation between the two constraints. In some interesting cases, the behavior was precisely such that the conjectures were mutually exclusive. Motivated by these works, we study the mass to charge and shear viscosity to entropy density ratios for charged AdS5 black branes, which are holographically dual to four-dimensional CFTs at finite temperature. We study a family of four-derivative and six-derivative perturbative corrections to these backgrounds. We identify the region in parameter space where the two constraints are satisfied and in particular find that the inclusion of the next-to-leading perturbative correction introduces wider possibilities for the satisfaction of both constraints.Comment: 24 pages, 6 figures, v2: published version, refs added, minor clarificatio

Search for Axionlike and Scalar Particles with the NA64 Experiment

We carried out a model-independent search for light scalar (s) and pseudoscalar axionlike (a) particles that couple to two photons by using the high-energy CERN SPS H4 electron beam. The new particles, if they exist, could be produced through the Primakoff effect in interactions of hard bremsstrahlung photons generated by 100 GeV electrons in the NA64 active dump with virtual photons provided by the nuclei of the dump. The a(s) would penetrate the downstream HCAL module, serving as shielding, and would be observed either through their $a(s)\to\gamma \gamma$ decay in the rest of the HCAL detector or as events with large missing energy if the a(s) decays downstream of the HCAL. This method allows for the probing the a(s) parameter space, including those from generic axion models, inaccessible to previous experiments. No evidence of such processes has been found from the analysis of the data corresponding to $2.84\times10^{11}$ electrons on target allowing to set new limits on the $a(s)\gamma\gamma$-coupling strength for a(s) masses below 55 MeV.Comment: This publication is dedicated to the memory of our colleague Danila Tlisov. 7 pages, 5 figures, revised version accepted for publication in Phys. Rev. Let

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

Computational Fitness Landscape for All Gene-Order Permutations of an RNA Virus

How does the growth of a virus depend on the linear arrangement of genes in its genome? Answering this question may enhance our basic understanding of virus evolution and advance applications of viruses as live attenuated vaccines, gene-therapy vectors, or anti-tumor therapeutics. We used a mathematical model for vesicular stomatitis virus (VSV), a prototype RNA virus that encodes five genes (N-P-M-G-L), to simulate the intracellular growth of all 120 possible gene-order variants. Simulated yields of virus infection varied by 6,000-fold and were found to be most sensitive to gene-order permutations that increased levels of the L gene transcript or reduced levels of the N gene transcript, the lowest and highest expressed genes of the wild-type virus, respectively. Effects of gene order on virus growth also depended upon the host-cell environment, reflecting different resources for protein synthesis and different cell susceptibilities to infection. Moreover, by computationally deleting intergenic attenuations, which define a key mechanism of transcriptional regulation in VSV, the variation in growth associated with the 120 gene-order variants was drastically narrowed from 6,000- to 20-fold, and many variants produced higher progeny yields than wild-type. These results suggest that regulation by intergenic attenuation preceded or co-evolved with the fixation of the wild type gene order in the evolution of VSV. In summary, our models have begun to reveal how gene functions, gene regulation, and genomic organization of viruses interact with their host environments to define processes of viral growth and evolution

Assessment of cartilage-dedicated sequences at ultra-high-field MRI: comparison of imaging performance and diagnostic confidence between 3.0 and 7.0 T with respect to osteoarthritis-induced changes at the knee joint

The objectives of the study were to optimize three cartilage-dedicated sequences for in vivo knee imaging at 7.0 T ultra-high-field (UHF) magnetic resonance imaging (MRI) and to compare imaging performance and diagnostic confidence concerning osteoarthritis (OA)-induced changes at 7.0 and 3.0 T MRI. Optimized MRI sequences for cartilage imaging at 3.0 T were tailored for 7.0 T: an intermediate-weighted fast spin-echo (IM-w FSE), a fast imaging employing steady-state acquisition (FIESTA) and a T1-weighted 3D high-spatial-resolution volumetric fat-suppressed spoiled gradient-echo (SPGR) sequence. Three healthy subjects and seven patients with mild OA were examined. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), diagnostic confidence in assessing cartilage abnormalities, and image quality were determined. Abnormalities were assessed with the whole organ magnetic resonance imaging score (WORMS). Focal cartilage lesions and bone marrow edema pattern (BMEP) were also quantified. At 7.0 T, SNR was increased (p < 0.05) for all sequences. For the IM-w FSE sequence, limitations with the specific absorption rate (SAR) required modifications of the scan parameters yielding an incomplete coverage of the knee joint, extensive artifacts, and a less effective fat saturation. CNR and image quality were increased (p < 0.05) for SPGR and FIESTA and decreased for IM-w FSE. Diagnostic confidence for cartilage lesions was highest (p < 0.05) for FIESTA at 7.0 T. Evaluation of BMEP was decreased (p < 0.05) at 7.0 T due to limited performance of IM-w FSE. Gradient echo-based pulse sequences like SPGR and FIESTA are well suited for imaging at UHF which may improve early detection of cartilage lesions. However, UHF IM-w FSE sequences are less feasible for clinical use

Search for Charged Higgs Bosons in e+e- Collisions at \sqrt{s} = 189 GeV

A search for pair-produced charged Higgs bosons is performed with the L3 detector at LEP using data collected at a centre-of-mass energy of 188.6 GeV, corresponding to an integrated luminosity of 176.4 pb^-1. Higgs decays into a charm and a strange quark or into a tau lepton and its associated neutrino are considered. The observed events are consistent with the expectations from Standard Model background processes. A lower limit of 65.5 GeV on the charged Higgs mass is derived at 95 % confidence level, independent of the decay branching ratio Br(H^{+/-} -> tau nu)