Oscillator strengths and line widths of dipole-allowed transitions in ¹⁴N₂ between 89.7 and 93.5 nm

Line oscillator strengths in the 20 electric dipole-allowed bands of ¹⁴N₂ in the 89.7–93.5nm (111480–106950cm⁻¹) region are reported from photoabsorptionmeasurements at an instrumental resolution of ∼6mÅ (0.7cm⁻¹) full width at half maximum. The absorptionspectrum comprises transitions to vibrational levels of the 3pσᵤc′₄¹Σᵤ⁺, 3pπᵤc³Πᵤ, and 3sσgo₃¹ΠᵤRydberg states and of the b′¹Σᵤ⁺ and b¹Πᵤ valence states. The J dependences of band f values derived from the experimental line f values are reported as polynomials in J′(J′+1) and are extrapolated to J′=0 in order to facilitate comparisons with results of coupled Schrödinger-equation calculations. Most bands in this study are characterized by a strong J dependence of the band f values and display anomalous P-, Q-, and R-branch intensity patterns. Predissociation line widths, which are reported for 11 bands, also exhibit strong J dependences. The f value and line width patterns can inform current efforts to develop comprehensive spectroscopic models that incorporate rotational effects and predissociation mechanisms, and they are critical for the construction of realistic atmospheric radiative-transfer models.This work was supported in part by NASA Grant No. NNG05GA03G to Wellesley College and Australian Research Council Discovery Program Grant No. DP0558962

Modeling the public health impact of malaria vaccines for developers and policymakers

Efforts to develop malaria vaccines show promise. Mathematical model-based estimates of the potential demand, public health impact, and cost and financing requirements can be used to inform investment and adoption decisions by vaccine developers and policymakers on the use of malaria vaccines as complements to existing interventions. However, the complexity of such models may make their outputs inaccessible to non-modeling specialists. This paper describes a Malaria Vaccine Model (MVM) developed to address the specific needs of developers and policymakers, who need to access sophisticated modeling results and to test various scenarios in a user-friendly interface. The model's functionality is demonstrated through a hypothetical vaccine.; The MVM has three modules: supply and demand forecast; public health impact; and implementation cost and financing requirements. These modules include pre-entered reference data and also allow for user-defined inputs. The model includes an integrated sensitivity analysis function. Model functionality was demonstrated by estimating the public health impact of a hypothetical pre-erythrocytic malaria vaccine with 85% efficacy against uncomplicated disease and a vaccine efficacy decay rate of four years, based on internationally-established targets. Demand for this hypothetical vaccine was estimated based on historical vaccine implementation rates for routine infant immunization in 40 African countries over a 10-year period. Assumed purchase price was $5 per dose and injection equipment and delivery costs were$0.40 per dose.; The model projects the number of doses needed, uncomplicated and severe cases averted, deaths and disability-adjusted life years (DALYs) averted, and cost to avert each. In the demonstration scenario, based on a projected demand of 532 million doses, the MVM estimated that 150 million uncomplicated cases of malaria and 1.1 million deaths would be averted over 10 years. This is equivalent to 943 uncomplicate cases and 7 deaths averted per 1,000 vaccinees. In discounted 2011 US dollars, this represents $11 per uncomplicated case averted and$1,482 per death averted. If vaccine efficacy were reduced to 75%, the estimated uncomplicated cases and deaths averted over 10 years would decrease by 14% and 19%, respectively.; The MVM can provide valuable information to assist decision-making by vaccine developers and policymakers, information which will be refined and strengthened as field studies progress allowing further validation of modeling assumptions

Reflection on-line or off-line: the role of learning technologies in encouraging students to reflect

This paper presents case studies that describe the experiences of the two authors in trying to use learning technologies to facilitate reflective thinking in their students. At the University of Leicester, a Web-based biology tutorial called ‘How Now Mad Cow’, which covers the topics of bovine spongiform encephalopathy and a new variant Creutzfeldt–Jakob disease (nvCJD). At the University of Southampton, a web-based hyper-mail discussion list to support teaching on a first year psychosocial science module for occupational therapy and physiotherapy students has been established. In both examples, the tutors had attempted to create a learning environment that would engage students in the learning experience and facilitate reflection by helping them to create meaning from the learning experience and see things in a different way. The evaluation data from both case studies provides some evidence that the learning technologies helped to facilitate reflection for some students. However, the evidence for reflection is not overwhelming and the data provides some evidence that four key factors may have influenced how successful the use of learning technologies were in facilitating reflection. These factors are the way the learning technology is used, the nature of the student groups, the role of the tutor and student preferences for ‘off-line reflection’. These are discussed and ways forward are identified

Oscillator strengths and line widths of dipole-allowed transitions in ¹⁴N₂ between 86.0 and 89.7 nm

Oscillator strengths of 23 electric-dipole-allowed bands of ¹⁴N₂ in the 86.0–89.7 nm (111 480–116 280 cm⁻¹) region are reported from synchrotron-based photoabsorptionmeasurements at an instrumental resolution of 6.5×10⁻⁴ nm (0.7 cm⁻¹) full width at half maximum.Partial support for this research was provided by the Australian Research Council Discovery Program through Grant No. DP0558962 and by NASA Grant No. NNX08AE786 to Wellesley College

Optimizations of the energy grid search algorithm in continuous-energy Monte Carlo particle transport codes

In this work we propose, implement, and test various optimizations of the typical energy grid-cross section pair lookup algorithm in Monte Carlo particle transport codes. The key feature common to all of the optimizations is a reduction in the length of the vector of energies that must be searched when locating the index of a particle's current energy. Other factors held constant, a reduction in energy vector length yields a reduction in CPU time. The computational methods we present here are physics-informed. That is, they are designed to utilize the physical information embedded in a simulation in order to reduce the length of the vector to be searched. More specifically, the optimizations take advantage of information about scattering kinematics, neutron cross section structure and data representation, and also the expected characteristics of a system's spatial flux distribution and energy spectrum. The methods that we present are implemented in the OpenMC Monte Carlo neutron transport code as part of this work. The gains in computational efficiency, as measured by overall code speedup, associated with each of the optimizations are demonstrated in both serial and multithreaded simulations of realistic systems. Depending on the system, simulation parameters, and optimization method employed, overall code speedup factors of 1.2-1.5, relative to the typical single-nuclide binary search algorithm, are routinely observed

Mannose binding lectin is required for alphavirus-induced arthritis/myositis

Mosquito-borne alphaviruses such as chikungunya virus and Ross River virus (RRV) are emerging pathogens capable of causing large-scale epidemics of virus-induced arthritis and myositis. The pathology of RRV-induced disease in both humans and mice is associated with induction of the host inflammatory response within the muscle and joints, and prior studies have demonstrated that the host complement system contributes to development of disease. In this study, we have used a mouse model of RRV-induced disease to identify and characterize which complement activation pathways mediate disease progression after infection, and we have identified the mannose binding lectin (MBL) pathway, but not the classical or alternative complement activation pathways, as essential for development of RRV-induced disease. MBL deposition was enhanced in RRV infected muscle tissue from wild type mice and RRV infected MBL deficient mice exhibited reduced disease, tissue damage, and complement deposition compared to wild-type mice. In contrast, mice deficient for key components of the classical or alternative complement activation pathways still developed severe RRV-induced disease. Further characterization of MBL deficient mice demonstrated that similar to C3(-/-) mice, viral replication and inflammatory cell recruitment were equivalent to wild type animals, suggesting that RRV-mediated induction of complement dependent immune pathology is largely MBL dependent. Consistent with these findings, human patients diagnosed with RRV disease had elevated serum MBL levels compared to healthy controls, and MBL levels in the serum and synovial fluid correlated with severity of disease. These findings demonstrate a role for MBL in promoting RRV-induced disease in both mice and humans and suggest that the MBL pathway of complement activation may be an effective target for therapeutic intervention for humans suffering from RRV-induced arthritis and myositis.This work was supported by NIH/NIAMS R01 AR 047190 awarded to MTH

Genome-wide expression profiling of in vivo-derived bloodstream parasite stages and dynamic analysis of mRNA alterations during synchronous differentiation in Trypanosoma brucei

Background: Trypanosomes undergo extensive developmental changes during their complex life cycle. Crucial among these is the transition between slender and stumpy bloodstream forms and, thereafter, the differentiation from stumpy to tsetse-midgut procyclic forms. These developmental events are highly regulated, temporally reproducible and accompanied by expression changes mediated almost exclusively at the post-transcriptional level. Results: In this study we have examined, by whole-genome microarray analysis, the mRNA abundance of genes in slender and stumpy forms of T. brucei AnTat1.1 cells, and also during their synchronous differentiation to procyclic forms. In total, five biological replicates representing the differentiation of matched parasite populations derived from five individual mouse infections were assayed, with RNAs being derived at key biological time points during the time course of their synchronous differentiation to procyclic forms. Importantly, the biological context of these mRNA profiles was established by assaying the coincident cellular events in each population (surface antigen exchange, morphological restructuring, cell cycle re-entry), thereby linking the observed gene expression changes to the well-established framework of trypanosome differentiation. Conclusion: Using stringent statistical analysis and validation of the derived profiles against experimentally-predicted gene expression and phenotypic changes, we have established the profile of regulated gene expression during these important life-cycle transitions. The highly synchronous nature of differentiation between stumpy and procyclic forms also means that these studies of mRNA profiles are directly relevant to the changes in mRNA abundance within individual cells during this well-characterised developmental transition.Publisher PDFPeer reviewe

A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin

The molecular basis for Toll-like receptor (TLR) recognition of microbial ligands is unknown. We demonstrate that mouse and human TLR5 discriminate between different flagellins, and we use this difference to map the flagellin recognition site on TLR5 to 228 amino acids of the extracellular domain. Through molecular modeling of the TLR5 ectodomain, we identify two conserved surface-exposed regions. Mutagenesis studies demonstrate that naturally occurring amino acid variation in TLR5 residue 268 is responsible for human and mouse discrimination between flagellin molecules. Mutations within one conserved surface identify residues D295 and D367 as important for flagellin recognition. These studies localize flagellin recognition to a conserved surface on the modeled TLR5 structure, providing detailed analysis of the interaction of a TLR with its ligand. These findings suggest that ligand binding at the β sheets results in TLR activation and provide a new framework for understanding TLR–agonist interactions

Globin gene expression in correlation with G protein-related genes during erythroid differentiation

Background: The guanine nucleotide binding protein (G protein)-coupled receptors (GPCRs) regulate cell growth, proliferation and differentiation. G proteins are also implicated in erythroid differentiation, and some of them are expressed principally in hematopoietic cells. GPCRs-linked NO/cGMP and p38 MAPK signaling pathways already demonstrated potency for globin gene stimulation. By analyzing erythroid progenitors, derived from hematopoietic cells through in vitro ontogeny, our study intends to determine early markers and signaling pathways of globin gene regulation and their relation to GPCR expression. Results: Human hematopoietic CD34(+) progenitors are isolated from fetal liver (FL), cord blood (CB), adult bone marrow (BM), peripheral blood (PB) and G-CSF stimulated mobilized PB (mPB), and then differentiated in vitro into erythroid progenitors. We find that growth capacity is most abundant in FL- and CB-derived erythroid cells. The erythroid progenitor cells are sorted as 100% CD71(+), but we did not find statistical significance in the variations of CD34, CD36 and GlyA antigens and that confirms similarity in maturation of studied ontogenic periods. During ontogeny, beta-globin gene expression reaches maximum levels in cells of adult blood origin (176 fmol/mu g), while gamma-globin gene expression is consistently up-regulated in CB-derived cells (60 fmol/mu g). During gamma-globin induction by hydroxycarbamide, we identify stimulated GPCRs (PTGDR, PTGER1) and GPCRs-coupled genes known to be activated via the cAMP/PKA (ADIPOQ), MAPK pathway (JUN) and NO/cGMP (PRPF18) signaling pathways. During ontogeny, GPR45 and ARRDC1 genes have the most prominent expression in FL-derived erythroid progenitor cells, GNL3 and GRP65 genes in CB-derived cells (high gamma-globin gene expression), GPR110 and GNG10 in BM-derived cells, GPR89C and GPR172A in PB-derived cells, and GPR44 and GNAQ genes in mPB-derived cells (high beta-globin gene expression). Conclusions: These results demonstrate the concomitant activity of GPCR-coupled genes and related signaling pathways during erythropoietic stimulation of globin genes. In accordance with previous reports, the stimulation of GPCRs supports the postulated connection between cAMP/PKA and NO/cGMP pathways in activation of.-globin expression, via JUN and p38 MAPK signaling

Male frequent attenders of general practice and their help seeking preferences

Background: Low rates of health service usage by men are commonly linked to masculine values and traditional male gender roles. However, not all men conform to these stereotypical notions of masculinity, with some men choosing to attend health services on a frequent basis, for a variety of different reasons. This study draws upon the accounts of male frequent attenders of the General Practitioner's (GP) surgery, examining their help-seeking preferences and their reasons for choosing services within general practice over other sources of support. Methods: The study extends thematic analysis of interview data from the Self Care in Primary Care study (SCinPC), a large scale multi-method evaluation study of a self care programme delivered to frequent attenders of general practice. Data were collected from 34 semi-structured interviews conducted with men prior to their exposure to the intervention. Results: The ages of interviewed men ranged from 16 to 72 years, and 91% of the sample (n= 31) stated that they had a current health condition. The thematic analysis exposed diverse perspectives within male help-seeking preferences and the decision-making behind men's choice of services. The study also draws attention to the large variation in men's knowledge of available health services, particularly alternatives to general practice. Furthermore, the data revealed some men's lack of confidence in existing alternatives to general practice. Conclusions: The study highlights the complex nature of male help-seeking preferences, and provides evidence that there should be no 'one size fits all' approach to male service provision. It also provides impetus for conducting further studies into this under researched area of interest. © 2011 WPMH GmbH