The host-range tdCE phenotype of Chandipura virus is determined by mutations in the polymerase gene

The emerging arbovirus Chandipura virus (CV) has been implicated in epidemics of acute encephalitis in India with high mortality rates. The isolation of temperature-dependent host-range (tdCE) mutants, which are impaired in growth at 39 °C in chick embryo (CE) cells but not in monkey cells, highlights a dependence on undetermined host factors. We have characterized three tdCE mutants, each containing one or more coding mutations in the RNA polymerase gene and two containing additional mutations in the attachment protein gene. Using reverse genetics, we showed that a single amino acid change in the virus polymerase of each mutant was responsible for the host-range specificity. In CE cells at the non-permissive temperature, the discrete cytoplasmic replication complexes seen in mammalian cells or at the permissive temperature in CE cells were absent with the tdCE mutants, consistent with the tdCE lesions causing disruption of the replication complexes in a host-dependent manner

'The most audacious and specific plan for knowledge, freedom and a better world': developing radical pathways to free, open journals

Developments in digital technology have the potential to transform academic journal publishing. Academic research can now be disseminated directly to academic networks and the wider public, in theory bypassing the need for traditional journal publishing structures, conventional journal publishers and their associated commercial practices and cost structures. Cost is a particularly pressing issue for Higher Education (HE) globally. In the last few decades the strategies adopted by journal publishers have led to increasingly steep and unsustainable costs for our academic libraries, the centralisation of publishing power in the hands of a few conglomerates, and the corporatisation of metricised data that overwhelmingly profits corporate capital and that has largely been developed through the donated labour of academics, librarians and academic institutions. In this article we explore briefly the history of scholarly communications shifts, and the implications of digital publication for law libraries and law journals. We argue for a change of ownership in the means of production and analyse some of the obstacles to achieving this. We show how radical Open Access (OA) alternatives can work, based upon a case study of two existing OA journals, and we conclude with measures by which radical OA journals can be increased within the cultures of legal research

Program for computing partial pressures from residual gas analyzer data

A computer program for determining the partial pressures of various gases from residual-gas-analyzer data is given. The analysis of the ion currents of 18 m/e spectrometer peaks allows the determination of 12 gases simultaneously. Comparison is made to ion-gage readings along with certain other control information. The output data are presented in both tabular and graphical form

Retrograde transport pathways utilised by viruses and protein toxins

A model has been presented for retrograde transport of certain toxins and viruses from the cell surface to the ER that suggests an obligatory interaction with a glycolipid receptor at the cell surface. Here we review studies on the ER trafficking cholera toxin, Shiga and Shiga-like toxins, Pseudomonas exotoxin A and ricin, and compare the retrograde routes followed by these protein toxins to those of the ER trafficking SV40 and polyoma viruses. We conclude that there is in fact no obligatory requirement for a glycolipid receptor, nor even with a protein receptor in a lipid-rich environment. Emerging data suggests instead that there is no common pathway utilised for retrograde transport by all of these pathogens, the choice of route being determined by the particular receptor utilised

Quantitative Trait Loci for Vegetative Traits in Perennial Ryegrass (\u3cem\u3eLolium Perenne\u3c/em\u3e L.)

Physiological (EP) research in forage grasses relates traits such as leaf elongation rate (LER), leaf elongation duration (LED), and leaf appearance interval (ALf), to forage yield (Chapman & Lemaire, 1993). This paper reveals preliminary quantitative trait locus (QTL) discovery for eight EP traits in perennial ryegrass. It also investigates the potential role of multivariate analyses such as principal component analysis (PCA) in QTL analysis of EP data

Diagnostic Pathways as Social and Participatory Practices: The Case of Herpes Simplex Encephalitis

Herpes simplex virus (HSV) encephalitis is a potentially devastating disease, with significant rates of mortality and co-morbidities. Although the prognosis for people with HSV encephalitis can be improved by prompt treatment with aciclovir, there are often delays involved in the diagnosis and treatment of the disease. In response, National Clinical Guidelines have been produced for the UK which make recommendations for improving the management of suspected viral encephalitis. However, little is currently known about the everyday experiences and processes involved in the diagnosis and care of HSV encephalitis. The reported study aimed to provide an account of the diagnosis and treatment of HSV encephalitis from the perspective of people who had been affected by the condition. Thirty narrative interviews were conducted with people who had been diagnosed with HSV encephalitis and their significant others. The narrative accounts reveal problems with gaining access to a diagnosis of encephalitis and shortfalls in care for the condition once in hospital. In response, individuals and their families work hard to obtain medical recognition for the problem and shape the processes of acute care. As a consequence, we argue that the diagnosis and management of HSV encephalitis needs to be considered as a participatory process, which is co-produced by health professionals, patients, and their families. The paper concludes by making recommendations for developing the current management guidelines by formalising the critical role of patients and their significant others in the identification, and treatment of, HSV encephalitis

Residual stress generation in tungsten-copper brazed joint using brazing alloy

Understanding the residual stress state in brazed joints is crucial for operational design and life time performance of the part in service. High magnitudes residual stresses are expected in the joined materials following cooling from brazing temperatures (≈950°C) due to large mismatches in material properties such as coefficient of thermal expansion and Young’s modulus. This study aims at further understanding of the generation and distribution of residual stresses when brazing tungsten to copper using a eutectic gold-copper brazing alloy. This configuration is potentially useful for future divertor designs. Finite Element Analysis (FEM) has been used to predict the brazing induced stresses and residual stress measurements were carried out on the brazed joint by X-ray diffraction (XRD) to validate the prediction model. Large residual stresses are predicted and measured in the tungsten; however there is disagreement in the sign of the stress. Predicted stresses are highly tensile in nature close to the brazing interface, whereas the measured stresses are highly compressive. The disagreement is believed to be caused by the model not accurately simulating the complex brazing process. Residual stress measurements on the copper were not possible due to texturing during brazing, grain growth and significant inelastic strains and deformations. Misalignment of parent materials was also observed to significantly affect residual stresses

Residual stress generations in brazed tungsten dissimilar joints

Understanding the residual stress state in brazed joints is crucial for the operational design and lifetime performance of the part in service. High-magnitude residual stresses are expected in the joined materials following cooling from brazing temperatures (≈950 °C) due to large mismatches in the thermal and mechanical properties. This paper aims at further understanding of the residual stresses caused when brazing tungsten to copper and tungsten to 316L austenitic steel using a eutectic gold-copper brazing alloy. These configurations are potentially useful for future diverter designs. Finite element analysis has been used to predict the brazing-induced stresses and residual stress measurements were carried out on the brazed joint by X-ray diffraction to validate the prediction model. Large residual stresses are predicted and measured in the tungsten; however, there is disagreement in the nature of the stress in the tungsten-copper configuration. Predicted stresses are highly tensile in nature close to the brazing interface, whereas the measured stresses are highly compressive. The disagreement is believed to be caused by the model not accurately simulating the complex brazing process. Residual stress measurements on the copper were not possible due to texturing during brazing, grain growth, and significant inelastic strains. There is excellent correlation between the measured and predicted stresses in the tungsten-316L configuration. High-tensile stresses were predicted in the tungsten (magnitude approximately 1000 MPa close to the braze interface) and high tensile stresses were measured (magnitude approximately 800 MPa in the same region). Joint misalignment of parent materials was also observed to significantly affect the residual stresses

Structure and Metal Binding Properties of ZnuA, a Periplasmic Zinc Transporter from \u3cem\u3eEscherichia coli\u3c/em\u3e

ZnuA is the periplasmic Zn2+-binding protein associated with the high-affinity ATP-binding cassette ZnuABC transporter from Escherichia coli. Although several structures of ZnuA and its homologs have been determined, details regarding metal ion stoichiometry, affinity, and specificity as well as the mechanism of metal uptake and transfer remain unclear. The crystal structures of E. coli ZnuA (Eco-ZnuA) in the apo, Zn2+-bound, and Co2+-bound forms have been determined. ZnZnuA binds at least two metal ions. The first, observed previously in other structures, is coordinated tetrahedrally by Glu59, His60, His143, and His207. Replacement of Zn2+ with Co2+ results in almost identical coordination geometry at this site. The second metal binding site involves His224 and several yet to be identified residues from the His-rich loop that is unique to Zn2+ periplasmic metal binding receptors. Electron paramagnetic resonance and X-ray absorption spectroscopic data on CoZnuA provide additional insight into possible residues involved in this second site. The second site is also detected by metal analysis and circular dichroism (CD) titrations. Eco-ZnuA binds Zn2+ (estimated K d \u3c 20 nM), Co2+, Ni2+, Cu2+, Cu+, and Cd2+, but not Mn2+. Finally, conformational changes upon metal binding observed in the crystal structures together with fluorescence and CD data indicate that only Zn2+ substantially stabilizes ZnuA and might facilitate recognition of ZnuB and subsequent metal transfer

Higher and lower supramolecular orders for the design of self-assembled heterochiral tripeptide hydrogel biomaterials

The self-assembly behaviour of the eight stereoisomers of Val\u2013Phe\u2013Phe tripeptides under physiological conditions is assessed by several spectroscopy and microscopy techniques. We report the first examples of self-organised hydrogels from tripeptides in the L\u2013D\u2013L or D\u2013L\u2013D configuration, besides the expected gels with the D\u2013L\u2013L or L\u2013D\u2013D configuration, thus widening the scope for using amino acid chirality as a tool to drive self-assembly. Importantly, the positions of D- and L-amino acids in the gelling tripeptides determine a higher or lower supramolecular order, which translates into macroscopic gels with different rheological properties and thermal behaviours. The more durable hydrogels perform well in cytotoxicity assays, and also as peptides in solution. An appropriate design of the chirality of self-assembling sequences thus allows for the fine-tuning of the properties of the gel biomaterials. In conclusion, this study adds key details of supramolecular organization that will assist in the ex novo design of assembling chiral small molecules for their use as biomaterials