Mapping of serotype-specific, immunodominant epitopes in the NS-4 region of hepatitis C virus (HCV):use of type-specific peptides to serologically differentiate infections with HCV types 1, 2, and 3

The effect of sequence variability between different types of hepatitis C virus (HCV) on the antigenicity of the NS-4 protein was investigated by epitope mapping and by enzyme-linked immunosorbent assay with branched oligopeptides. Epitope mapping of the region between amino acid residues 1679 and 1768 in the HCV polyprotein revealed two major antigenic regions (1961 to 1708 and 1710 to 1728) that were recognized by antibody elicited upon natural infection of HCV. The antigenic regions were highly variable between variants of HCV, with only 50 to 60% amino acid sequence similarity between types 1, 2, and 3. Although limited serological cross-reactivity between HCV types was detected between peptides, particularly in the first antigenic region of NS-4, type-specific reactivity formed the principal component of the natural humoral immune response to NS-4. Type-specific antibody to particular HCV types was detected in 89% of the samples from anti-HCV-positive blood donors and correlated almost exactly with genotypic analysis of HCV sequences amplified from the samples by polymerase chain reaction. Whereas almost all blood donors appeared to be infected with a single virus type (97%), a higher proportion of samples (40%) from hemophiliacs infected from transfusion of non-heat-inactivated clotting factor contained antibody to two or even all three HCV types, providing evidence that long-term exposure may lead to multiple infection with different variants of HCV

Design and Shape Optimization of Strain Gauge Load Cell for Axial Force Measurement for Test Benches

The load cell is an indispensable component of many engineering machinery and industrial automation for measuring and sensing force and torque. This paper describes the design and analysis of the strain gauge load cell, from the conceptional design stage to shape optimization (based on the finite element method (FEM) technique) and calibration, providing ample load capacity with low-cost material (aluminum 6061) and highly accurate force measurement. The amplifier circuit of the half Wheatstone bridge configuration with two strain gauges was implemented experimentally with an actual load cell prototype. The calibration test was conducted to evaluate the load cell characteristics and derive the governing equation for sensing the unknown load depending on the measured output voltage. The measured sensitivity of the load cell is approximately 15 mV/N and 446.8 µV/V at a maximum applied load of 30 kg. The findings are supported by FEM results and experiments with an acceptable percentage of errors, which revealed an overall error of 6% in the worst situation. Therefore, the proposed load cell meets the design considerations for axial force measurement for the laboratory test bench, which has a light weight of 20 g and a maximum axial force capacity of 300 N with good sensor characteristic

Air Pollution and Lymphocyte Phenotype Proportions in Cord Blood

Effects of air pollution on morbidity and mortality may be mediated by alterations in immune competence. In this study we examined short-term associations of air pollution exposures with lymphocyte immunophenotypes in cord blood among 1,397 deliveries in two districts of the Czech Republic. We measured fine particulate matter < 2.5 μm in diameter (PM(2.5)) and 12 polycyclic aromatic hydrocarbons (PAHs) in 24-hr samples collected by versatile air pollution samplers. Cord blood samples were analyzed using a FACSort flow cytometer to determine phenotypes of CD3(+) T-lymphocytes and their subsets CD4(+) and CD8(+), CD19(+) B-lymphocytes, and natural killer cells. The mothers were interviewed regarding sociodemographic and lifestyle factors, and medical records were abstracted for obstetric, labor and delivery characteristics. During the period 1994 to 1998, the mean daily ambient concentration of PM(2.5) was 24.8 μg/m(3) and that of PAHs was 63.5 ng/m(3). In multiple linear regression models adjusted for temperature, season, and other covariates, average PAH or PM(2.5) levels during the 14 days before birth were associated with decreases in T-lymphocyte phenotype fractions (i.e., CD3(+) CD4(+), and CD8(+)), and a clear increase in the B-lymphocyte (CD19(+)) fraction. For a 100-ng/m(3) increase in PAHs, which represented approximately two standard deviations, the percentage decrease was −3.3% [95% confidence interval (CI), −5.6 to −1.0%] for CD3(+), −3.1% (95% CI, −4.9 to −1.3%) for CD4(+), and −1.0% (95% CI, −1.8 to −0.2%) for CD8(+) cells. The corresponding increase in the CD19(+) cell proportion was 1.7% (95% CI, 0.4 to 3.0%). Associations were similar but slightly weaker for PM(2.5). Ambient air pollution may influence the relative distribution of lymphocyte immunophenotypes of the fetus

On the computation of zone and double zone diagrams

Classical objects in computational geometry are defined by explicit relations. Several years ago the pioneering works of T. Asano, J. Matousek and T. Tokuyama introduced "implicit computational geometry", in which the geometric objects are defined by implicit relations involving sets. An important member in this family is called "a zone diagram". The implicit nature of zone diagrams implies, as already observed in the original works, that their computation is a challenging task. In a continuous setting this task has been addressed (briefly) only by these authors in the Euclidean plane with point sites. We discuss the possibility to compute zone diagrams in a wide class of spaces and also shed new light on their computation in the original setting. The class of spaces, which is introduced here, includes, in particular, Euclidean spheres and finite dimensional strictly convex normed spaces. Sites of a general form are allowed and it is shown that a generalization of the iterative method suggested by Asano, Matousek and Tokuyama converges to a double zone diagram, another implicit geometric object whose existence is known in general. Occasionally a zone diagram can be obtained from this procedure. The actual (approximate) computation of the iterations is based on a simple algorithm which enables the approximate computation of Voronoi diagrams in a general setting. Our analysis also yields a few byproducts of independent interest, such as certain topological properties of Voronoi cells (e.g., that in the considered setting their boundaries cannot be "fat").Comment: Very slight improvements (mainly correction of a few typos); add DOI; Ref [51] points to a freely available computer application which implements the algorithms; to appear in Discrete & Computational Geometry (available online

Ongoing mumps outbreak in a student population with high vaccination coverage, Netherlands, 2010.

Since December 2009, mumps incidence has increased in the Netherlands. As of 20 April 2010, 172 cases have been notified on the basis of laboratory confirmation or linkage to a laboratory-confirmed case. Of these, 112 were students, the majority of whom had been vaccinated (81%). Although outbreaks in vaccinated populations have been described before, risk factors for exposure and susceptibility, and dose-dependent vaccine effectiveness in a student population of this nature are relatively unknown

A multi-method approach for the integrative assessment of soil functions: Application on a coastal mountainous site of the Philippines

The projected increase of the world\u27s population and the sustainability challenges the agricultural sector is facing, call for the enhancement of multi-functionality in agriculture in order to simultaneously provide food while meeting environmental targets. Here, we use the Functional Land Management (FLM) framework to assess the supply of and the demand for soil functions to inform agri-environmental policy for Udalo, a mountainous site in the Philippines. As many emerging communities in developing nations, Udalo is on the cusp of rapid development due to the construction of a major road increasing its accessibility and attractiveness for land investment. We assessed the supply of four soil functions in relation to six land-use types and four slope categories. The function “productivity” was assessed by interviews with 128 farmers, “habitat for biodiversity” by a vegetation survey, and “soil conservation” and “water conservation” via a literature review. The demand for functions was first assessed from the “top-down” policy perspective via interviews and reviews of policy targets, then complemented by integrating the local “bottom-up” demands for functions. These were assessed by applying a Q methodology, providing insights in the prioritisation of functions from the perspective of 22 local actors. Maps of supply and demands were generated for each function: supply maps by overlaying land use and slope category, top-down demand maps from administrative zoning/land-use plans, and bottom-up demand maps from local actors designation of geomorphological areas. Our results revealed contrasting demands for functions, as well as a heterogeneous spatial distribution of supply and demands. Discrepancies emerged (i) between supply and demand, (ii) between bottom-up (local) demands and the top-down (policy driven) demand, and (iii) among local actors perspectives. Our study indicates that discrepancies are not necessarily conflicting, but can uncover pathways for defining compromises, representing attainable policy entry points. Not one single development model can meet the needs of every stakeholder; however, a combination of land uses and management strategies can meet divergent interests and allow for optimisation of functions. This integrative approach of FLM provides a socially embedded biophysical analysis and is a valuable tool for the design of customized land-use and agri-environmental policies

Transdisciplinary learning: Transformative collaborations between students, industry, academia and communities.

Background and objectives of the case An analogy: Imagine you are invited to a dinner party, but instead of a stuffy sit-down affair, your host asks you to bring your favourite ingredient, and together you prepare a delicious feast of unique and distinct flavours. UTS’s transdisciplinary initiatives are changing the shape of higher education and forging innovative partnerships by bringing together diverse professional fields. With a focus on practice-based and problem-focused learning, UTS educational programs combine the strengths of multiple disciplines, industries, public sector organisations, and the community to turn real-world problems into rewarding opportunities for education and also “learning for a lifetime”. In place of the limitations of artificial disciplinary boundaries, transdisciplinary learning practices create synergistic and innovative approaches to grappling with complex applied challenges. Students, researchers, practitioners, community members and other stakeholders combine their knowledge, tools, techniques, methods, theories, concepts, as well as cultural and personal perspectives. By understanding problems holistically, the solutions that emerge are bold, innovative, and creative, as well as mutually beneficial. We view this as the future of education: good to work with, and good to think with — problem solving for (and with) industry and society. The Faculty of Transdisciplinary Innovation is re-imagining how education, research, and professional practice can work together to navigate today’s complex problems, and create commercially attractive and socially responsible futures. We also practice what we preach: for example, staff professional development to enact these models in our own teaching; educational programs to provide experiential learning around problem solving within a rapidly-changing environment involving students from across different disciplines and cultural backgrounds; as well as policy development and research on today’s pressing “wicked problems” with industry and government. Primary objectives of this next practice concept of transdisciplinary learning, include: - To promote a shift in industry-university engagement from producing “knowledge for society” to co-generating “knowledge with society”; - To build a resilient ecosystem for co-learning; - To create and sustain future-oriented degree programs with collaboration between industry, government, and community at the centre, geared to prepare our graduates for the complex challenges of a networked world; - To create an agile and responsive industry-university lab environment for generating and testing new experimental models; - To enable industry – by collaborating with our students and academics – to see their problems from a fresh perspective, often through different and revealing lenses, and to notice opportunities and spot challenges that may have otherwise been overlooked; - To prepare students to lead innovation in a rapidly-changing and challenging world; and - To graduate students who are ‘complexity-fluent’, systems thinkers, creative problem-posers and -solvers, and imaginative, ethical citizens

Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al

Decentralized motion planning for multiple mobile robots: The cocktail party model

Abstract. This paper presents an approach for decentralized real-time motion planning for multiple mobile robots operating in a common 2-dimensional environment with unknown stationary obstacles. In our model, a robot can see (sense) the surrounding objects. It knows its current and its target’s position, is able to distinguish a robot from an obstacle, and can assess the instantaneous motion of another robot. Other than this, a robot has no knowledge about the scene or of the paths and objectives of other robots. There is no mutual communication among the robots; no constraints are imposed on the paths or shapes of robots and obstacles. Each robot plans its path toward its target dynamically, based on its current position and the sensory feedback; only the translation component is considered for the planning purposes. With this model, it is clear that no provable motion planning strategy can be designed (a simple example with a dead-lock is discussed); this naturally points to heuristic algorithms. The suggested strategy is based on maze-searching techniques. Computer simulation results are provided that demonstrate good performance and a remarkable robustness of the algorithm (meaning by this a virtual impossibility to create a dead-lock in a “random ” scene). Keywords: mobile robots, autonomous agents, decentralized intelligence, robot motion plannin

Graft-vs-tumor effect in patients with advanced nasopharyngeal cancer treated with nonmyeloablative allogeneic PBSC transplantation

While nonmyeloablative peripheral blood stem cell transplantation (NST) has shown efficacy against several solid tumors, it is untested in nasopharyngeal cancer (NPC). In a phase II clinical trial, 21 patients with pretreated metastatic NPC underwent NST with sibling PBSC allografts, using CY conditioning, thymic irradiation and in vivo T-cell depletion with thymoglobulin. Stable lymphohematopoietic chimerism was achieved in most patients and prophylactic CYA was tapered at a median of day +30. Seven patients (33%) showed partial response and three (14%) achieved stable disease. Four patients were alive at 2 years and three showed prolonged disease control of 344, 525 and 550 days. With a median follow-up of 209 (4–1147) days, the median PFS was 100 days (95% confidence interval (CI), 66–128 days), and median OS was 209 days (95% CI, 128–236 days). Patients with chronic GVHD had better survival—median OS 426 days (95% CI, 194–NE days) vs 143 days (95% CI, 114–226 days) (P=0.010). Thus, NST may induce meaningful clinical responses in patients with advanced NPC