Anticipating the species jump: surveillance for emerging viral threats.

Zoonotic disease surveillance is typically triggered after animal pathogens have already infected humans. Are there ways to identify high-risk viruses before they emerge in humans? If so, then how and where can identifications be made and by what methods? These were the fundamental questions driving a workshop to examine the future of predictive surveillance for viruses that might jump from animals to infect humans. Virologists, ecologists and computational biologists from academia, federal government and non-governmental organizations discussed opportunities as well as obstacles to the prediction of species jumps using genetic and ecological data from viruses and their hosts, vectors and reservoirs. This workshop marked an important first step towards envisioning both scientific and organizational frameworks for this future capability. Canine parvoviruses as well as seasonal H3N2 and pandemic H1N1 influenza viruses are discussed as exemplars that suggest what to look for in anticipating species jumps. To answer the question of where to look, prospects for discovering emerging viruses among wildlife, bats, rodents, arthropod vectors and occupationally exposed humans are discussed. Finally, opportunities and obstacles are identified and accompanied by suggestions for how to look for species jumps. Taken together, these findings constitute the beginnings of a conceptual framework for achieving a virus surveillance capability that could predict future species jumps

The Long Term Behaviour of Day-to-Day Traffic Assignment Models

The dynamical behaviour of deterministic process, day-to-day traffic assignment models is sometimes characterised by convergence to a variety of different fixed equilibrium points dependent upon the initial flow pattern, even though individual trajectories are unique for a given start point. This non-uniqueness is seemingly in sharp contrast to the evolution of stochastic process, day-to-day models; under certain assumptions these converge in law to a unique stationary distribution, irrespective of the start point. In this article, we show how models may be constructed which exhibit characteristics of both deterministic models and stochastic models, and illustrate the ideas by using a simple example network

Reprocessable thermosets for sustainable three-dimensional printing

Among all three-dimensional (3D) printing materials, thermosetting photopolymers claim almost half of the market, and have been widely used in various fields owing to their superior mechanical stability at high temperatures, excellent chemical resistance as well as good compatibility with high-resolution 3D printing technologies. However, once these thermosetting photopolymers form 3D parts through photopolymerization, the covalent networks are permanent and cannot be reprocessed, i.e., reshaped, repaired, or recycled. Here, we report a two-step polymerization strategy to develop 3D printing reprocessable thermosets (3DPRTs) that allow users to reform a printed 3D structure into a new arbitrary shape, repair a broken part by simply 3D printing new material on the damaged site, and recycle unwanted printed parts so the material can be reused for other applications. These 3DPRTs provide a practical solution to address environmental challenges associated with the rapid increase in consumption of 3D printing materials

Are L-myc genotypes prognostic markers in non-small cell lung carcinoma (NSCLC) in our Chinese patients?

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P53 intron 2 polymorphisms and mutations in non-small cell lung carcinoma in Hong Kong

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Computing Topology Preservation of RBF Transformations for Landmark-Based Image Registration

In image registration, a proper transformation should be topology preserving. Especially for landmark-based image registration, if the displacement of one landmark is larger enough than those of neighbourhood landmarks, topology violation will be occurred. This paper aim to analyse the topology preservation of some Radial Basis Functions (RBFs) which are used to model deformations in image registration. Mat\'{e}rn functions are quite common in the statistic literature (see, e.g. \cite{Matern86,Stein99}). In this paper, we use them to solve the landmark-based image registration problem. We present the topology preservation properties of RBFs in one landmark and four landmarks model respectively. Numerical results of three kinds of Mat\'{e}rn transformations are compared with results of Gaussian, Wendland's, and Wu's functions

Differential gene expression of the honey bee Apis mellifera associated with Varroa destructor infection

Background: The parasitic mite, Varroa destructor, is the most serious pest of the western honey bee, Apis mellifera, and has caused the death of millions of colonies worldwide. This mite reproduces in brood cells and parasitizes immature and adult bees. We investigated whether Varroa infestation induces changes in Apis mellifera gene expression, and whether there are genotypic differences that affect gene expression relevant to the bee's tolerance, as first steps toward unravelling mechanisms of host response and differences in susceptibility to Varroa parasitism. Results: We explored the transcriptional response to mite parasitism in two genetic stocks of A. mellifera which differ in susceptibility to Varroa, comparing parasitized and non-parasitized full-sister pupae from both stocks. Bee expression profiles were analyzed using microarrays derived from honey bee ESTs whose annotation has recently been enhanced by results from the honey bee genome sequence. We measured differences in gene expression in two colonies of Varroa-susceptible and two colonies of Varroa-tolerant bees. We identified a set of 148 genes with significantly different patterns of expression: 32 varied with the presence of Varroa, 116 varied with bee genotype, and 2 with both. Varroa parasitism caused changes in the expression of genes related to embryonic development, cell metabolism and immunity. Bees tolerant to Varroa were mainly characterized by differences in the expression of genes regulating neuronal development, neuronal sensitivity and olfaction. Differences in olfaction and sensitivity to stimuli are two parameters that could, at least in part, account for bee tolerance to Varroa; differences in olfaction may be related to increased grooming and hygienic behavior, important behaviors known to be involved in Varroa tolerance. Conclusion: These results suggest that differences in behavior, rather than in the immune system, underlie Varroa tolerance in honey bees, and give an indication of the specific physiological changes found in parasitized bees. They provide a first step toward better understanding molecular pathways involved in this important host-parasite relationshi

Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2

<p>Abstract</p> <p>Background</p> <p>The HER2-inhibiting antibody trastuzumab, in combination with chemotherapy, significantly improves survival of women with resected, HER2-overexpressing breast cancers, but is associated with toxicities including a risk of cardiomyopathy. Additionally, the beneficial effect of trastuzumab is expected to decrease once the drug is discontinued. We proposed to address these concerns by using cancer vaccines to stimulate HER2 intracellular domain (ICD)-specific T cell and antibody responses.</p> <p>Methods</p> <p>Subjects with stage II (≥ 6 +LN), III, or stage IV breast cancerwith > 50% HER2 overexpressing tumor cells who were disease-free after surgery and adjuvant therapy were eligible. Vaccines consisted of immature, cultured DC (n = 3), mature cultured DC (n = 3), or mature Flt3-ligand mobilized peripheral blood DC (n = 1) loaded with ICD, or tetanus toxoid, keyhole limpet hemocyanin or CMV peptide as controls, and were administered intradermally/subcutaneously four times at 3 week intervals. ICD-specific T cell and antibody responses were measured. Cardiac function was determined by MUGA or ECHO; long term disease status was obtained from patient contact.</p> <p>Results</p> <p>All seven patients successfully underwent DC generation and five received all 4 immunizations. There were no toxicities greater than grade 1 or ejection fraction decrements below normal. Delayed-type hypersensitivity (DTH) reactions at the injection site occurred in 6/7 patients and HER2 specificity was detected by cytokine flow cytometry or ELISPOT in 5 patients. At more than 5 years of follow-up, 6/7 had detectable anti-ICD antibodies. One patient experienced a pulmonary recurrence at 4 years from their study immunizations. This recurrence was resected and they are without evidence of disease. All patients are alive and disease-free at 4.6–6.7 years of follow-up.</p> <p>Conclusion</p> <p>Although this was a small pilot study, the well-tolerated nature of the vaccines, the lack of cardiac toxicity, significant immunogenicity, and a 100% 4.5-year survival rate suggest that vaccination with HER2 ICD protein-containing DC is appropriate for further study in this population.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00005956</p