WorldWideScience

Sample records for challenging strain targeting

  1. Live Attenuated Borrelia burgdorferi Targeted Mutants in an Infectious Strain Background Protect Mice from Challenge Infection.

    Science.gov (United States)

    Hahn, Beth L; Padmore, Lavinia J; Ristow, Laura C; Curtis, Michael W; Coburn, Jenifer

    2016-08-01

    Borrelia burgdorferi, B. garinii, and B. afzelii are all agents of Lyme disease in different geographic locations. If left untreated, Lyme disease can cause significant and long-term morbidity, which may continue after appropriate antibiotic therapy has been administered and live bacteria are no longer detectable. The increasing incidence and geographic spread of Lyme disease are renewing interest in the vaccination of at-risk populations. We took the approach of vaccinating mice with two targeted mutant strains of B. burgdorferi that, unlike the parental strain, are avirulent in mice. Mice vaccinated with both strains were protected against a challenge with the parental strain and a heterologous B. burgdorferi strain by either needle inoculation or tick bite. In ticks, the homologous strain was eliminated but the heterologous strain was not, suggesting that the vaccines generated a response to antigens that are produced by the bacteria both early in mammalian infection and in the tick. Partial protection against B. garinii infection was also conferred. Protection was antibody mediated, and reactivity to a variety of proteins was observed. These experiments suggest that live attenuated B. burgdorferi strains may be informative regarding the identification of protective antigens produced by the bacteria and recognized by the mouse immune system in vivo Further work may illuminate new candidates that are effective and safe for the development of Lyme disease vaccines. PMID:27335385

  2. Five challenges in modelling interacting strain dynamics

    Directory of Open Access Journals (Sweden)

    Paul S. Wikramaratna

    2015-03-01

    Full Text Available Population epidemiological models where hosts can be infected sequentially by different strains have the potential to help us understand many important diseases. Researchers have in recent years started to develop and use such models, but the extra layer of complexity from multiple strains brings with it many technical challenges. It is therefore hard to build models which have realistic assumptions yet are tractable. Here we outline some of the main challenges in this area. First we begin with the fundamental question of how to translate from complex small-scale dynamics within a host to useful population models. Next we consider the nature of so-called “strain space”. We describe two key types of host heterogeneities, and explain how models could help generate a better understanding of their effects. Finally, for diseases with many strains, we consider the challenge of modelling how immunity accumulates over multiple exposures.

  3. Five challenges in modelling interacting strain dynamics

    DEFF Research Database (Denmark)

    Wikramaratna, Paul S; Kurcharski, Adam; Gupta, Sunetra;

    2015-01-01

    Population epidemiological models where hosts can be infected sequentially by different strains have the potential to help us understand many important diseases. Researchers have in recent years started to develop and use such models, but the extra layer of complexity from multiple strains brings...... with it many technical challenges. It is therefore hard to build models which have realistic assumptions yet are tractable. Here we outline some of the main challenges in this area. First we begin with the fundamental question of how to translate from complex small-scale dynamics within a host to...... useful population models. Next we consider the nature of so-called “strain space”. We describe two key types of host heterogeneities, and explain how models could help generate a better understanding of their effects. Finally, for diseases with many strains, we consider the challenge of modelling how...

  4. A laser strain gauge for accelerator targets

    International Nuclear Information System (INIS)

    Multi megawatt accelerators can deliver sufficient power to a target to destroy it in a few pulses. In order to look at the response of solid and liquid targets under these high power pulses, we are developing optical methods of measuring surface deformations with time resolutions limited by laser pulse lengths. These methods can be used to examine the surfaces of solids and liquids during elastic deformation and unstable hydrodynamic flows. We present preliminary results of a system designed for target tests using the Brookhaven AGS and the Argonne CHM linac

  5. Inflation Targeting at 20 - Achievements and Challenges

    OpenAIRE

    Scott Roger

    2009-01-01

    This paper provides an overview of inflation targeting frameworks and macroeconomic performance under inflation targeting. Inflation targeting frameworks are generally quite similar across countries, and a broad consensus has developed in favor of "flexible" inflation targeting. The evidence shows that, although inflation target ranges are missed frequently in most countries, the inflation and growth performance under inflation targeting compares very favorably with performance under alternat...

  6. Differential detection of classical swine fever virus challenge strains in C-strain vaccinated pigs

    OpenAIRE

    Everett, Helen E.; Crudgington, Bentley S; Sosan-Soulé, Olubukola; Crooke, Helen R.

    2014-01-01

    Background Control of classical swine fever (CSF) by vaccination ideally requires that field strain infection can be detected irrespective of the vaccination status of the herd. To inform on the usefulness of molecular tests compatible with genetic Differentiation of Infected from Vaccinated Animals (DIVA) principles when using live-attenuated vaccines, tonsil homogenates from a vaccination-challenge experiment were analyzed using a differential real-time qRT-PCR for the C-strain vaccine or r...

  7. Target Value Design: The Challenge of Value Generation

    OpenAIRE

    Gomes Miron, Luciana; Kaushik, Amit; Koskela, Lauri

    2015-01-01

    Target Value Design (TVD) is a management approach that aims to maximize value in the framework of a pre-established cost target. TVD views AEC (Architecture, Engineering and Construction) as a complex system and transforms the current design practice upside down. In spite of the existing studies, applying TVD in the context of AEC still represents a major challenge. Creating a structure that enables and measures value generation to the client is part of this challenge. However, despite the c...

  8. Listeria monocytogenes: Strain Heterogeneity, Methods, and Challenges of Subtyping.

    Science.gov (United States)

    Nyarko, Esmond B; Donnelly, Catherine W

    2015-12-01

    Listeria monocytogenes is a food-borne bacterial pathogen that is associated with 20% to 30% case fatality rate. L. monocytogenes is a genetically heterogeneous species, with a small fraction of strains (serotypes 1/2a, 1/2b, 4b) implicated in human listeriosis. Monitoring and source tracking of L. monocytogenes involve the use of subtyping methods, with the performance of genetic-based methods found to be superior to phenotypic-based ones. Various methods have been used to subtype L. monocytogenes isolates, with the pulsed-field gel electrophoresis (PFGE) being the gold standard. Although PFGE has had a massive impact on food safety through the establishment of the PulseNet, there is no doubt that whole genome sequence (WGS) typing is accurate, has a discriminatory power superior to any known method, and allows genome-wide differences between strains to be quantified through the comparison of nucleotide sequences. This review focuses on the different techniques that have been used to type L. monocytogenes strains, their performance challenges, and the tremendous impact WGS typing could have on the food safety landscape. PMID:26588067

  9. Targeted nanodrugs for cancer therapy: prospects and challenges.

    Science.gov (United States)

    Bottini, Massimo; Sacchetti, Cristiano; Pietroiusti, Antonio; Bellucci, Stefano; Magrini, Andrea; Rosato, Nicola; Bottini, Nunzio

    2014-01-01

    The recent advent of nanomedicine holds potential to revolutionize cancer therapy. This innovative discipline has paved the way for the emergence of a new class of drugs based on nanoengineered particles. These "nanodrugs" are designed to greatly enhance drug therapeutic indices. First-generation nanodrugs consisted of conventional anti-cancer drugs loaded into/onto nanoengineered particles (nanocarriers) devoid of targeting features (non-targeted nanodrugs). Non-targeted nanodrugs have provided the opportunity to carry large amounts of drugs, including poorly water-soluble and/or permeable drugs, to several types of tumors, improving the therapeutic index with respect to comparable free drugs. Although effective, the primary delivery mechanism of non-targeted nanodrugs was through passive tissue accumulation, due to pathophysiological differences between tumor-associated and healthy vessels, and through non-specific targeting of cell subsets, posing the danger of off-target binding and effects. Recently, the therapeutic indices of certain anti-cancer drugs were further improved by attaching targeting ligands to nanodrugs (targeted-nanodrugs). Targeted-nanodrugs selectively bind to cognate receptors expressed on target cells and enter cells more efficiently than non-targeted formulations. Although these advancements have been sufficiently beneficial to place targeted-nanodrugs into clinical development for use in cancer therapy, they also come at a price. The addition of ligands to drug-loaded nanocarriers often leads to additional synthesis steps and costs, and more complex biological performance relative to ligand-devoid nanodrugs. Here, we will discuss the benefits and challenges facing the addition of targeting features to nanodrugs for cancer therapy. PMID:24730253

  10. The challenges associated with molecular targeted therapies for glioblastoma.

    Science.gov (United States)

    Jue, Toni Rose; McDonald, Kerrie L

    2016-05-01

    Glioblastoma (GBM) is the most aggressive malignant brain tumor in adults. Improvements in the treatment of GBM have remained static since the advent of the standard therapy which includes radiation with concurrent and adjuvant temozolomide treatment. Developing treatment and diagnostic or companion biomarker combinations is transforming the way we treat numerous cancers. However, can this emerging paradigm be also effective for GBM? Can GBM be treated the same way as other cancers? Here we review the challenges for a personalized molecular targeted therapeutic approach in GBM. The specific challenges for establishing a personalized molecular targeted medicine program for GBM patients include overcoming the blood brain barrier, unravelling the intra- and inter-heterogeneity that exists and the importance of developing more relevant animal models that recapitulate a patient's GBM tumor. PMID:26900075

  11. RADIATION-RESISTANT FIBER OPTIC STRAIN SENSORS FOR SNS TARGET INSTRUMENTATION

    Energy Technology Data Exchange (ETDEWEB)

    Blokland, Willem [ORNL; Bryan, Jeff [ORNL; Riemer, Bernie [ORNL; Sangrey, Robert L [ORNL; Wendel, Mark W [ORNL; Liu, Yun [ORNL

    2016-01-01

    Measurement of stresses and strains in the mercury tar-get vessel of the Spallation Neutron Source (SNS) is important to understand the structural dynamics of the target. This work reports the development of radiation-resistant fiber optic strain sensors for the SNS target in-strumentation.

  12. Comparison of the pathogenicity of the USDA challenge virus strain to a field strain of infectious laryngotracheitis virus.

    Science.gov (United States)

    Koski, Danielle M; Predgen, Ann S; Trampel, Darrell W; Conrad, Sandra K; Narwold, Debra R; Hermann, Joseph R

    2015-07-01

    Infectious laryngotracheitis virus (ILTV) causes respiratory disease in chickens. This alphaherpesvirus infects laryngeal tracheal epithelial cells and causes outbreaks culminating in decreases in egg production, respiratory distress in chickens and mortality. There are several different vaccines to combat symptoms of the virus, including chicken embryo origin, tissue culture origin and recombinant vaccines. All vaccines licensed for use in the U.S. are tested for efficacy and potency according to U.S. federal regulation using a vaccine challenge assay involving the use of an ILT challenge virus. This challenge virus is provided to biologics companies by the Center for Veterinary Biologics (CVB), United States Department of Agriculture (USDA). The current USDA challenge virus originated from a vaccine strain and has been subjected to multiple passages in eggs, and may not represent what is currently circulating in the field. The objective of this study was to evaluate and compare the pathogenicity of USDA's challenge virus strain to the pathogenicity of a recent ILT field isolate. Using the challenge virus and various dilutions of the field isolate, clinical signs, mortality and pathology were evaluated in chickens. Results indicate that the field isolate at a 1:20 dilution is comparable in pathogenicity to the USDA challenge virus at a 1:4 dilution, and that the ILTV field isolate is a viable candidate that could be used as a challenge virus when evaluating vaccine efficacy. PMID:26050912

  13. Heat strain in personal protective clothing: Challenges and intervention strategies

    NARCIS (Netherlands)

    McLellan, T.M.; Daanen, H.A.M.

    2012-01-01

    Humans rely on sweat evaporation during exercise in the heat to promote cooling and to maintain thermal homeostasis. In protective clothing, however, sweat evaporation is severely hampered and this may lead to uncompensable heat strain, where core body temperature continues to rise leading to physic

  14. A review of advances and challenges in EBSD strain mapping

    Science.gov (United States)

    Wilkinson, A. J.; Britton, T. B.; Jiang, J.; Karamched, P. S.

    2014-03-01

    High sensitivity cross-correlation based analysis of EBSD patterns was introduced by Wilkinson, Meaden and Dingley in 2006 [1, 2]. This paper will describe the basis of the method and the various modifications and improvements that have been made to it over the past few years. Strain sensitivity of ~ 10-4 is readily obtained and sensitivity to lower strains is achievable if signal to noise ratio in the patterns is improved by simple integration. The method allows maps of local stress and dislocation density distributions to be generated in parallel with information concerning grain orientation, grain boundary misorientation and the presence of other microstructural features. The method is illustrated by example maps from a Ni-based superalloy and deformed Cu.

  15. A review of advances and challenges in EBSD strain mapping

    International Nuclear Information System (INIS)

    High sensitivity cross-correlation based analysis of EBSD patterns was introduced by Wilkinson, Meaden and Dingley in 2006 [1, 2]. This paper will describe the basis of the method and the various modifications and improvements that have been made to it over the past few years. Strain sensitivity of ∼ 10−4 is readily obtained and sensitivity to lower strains is achievable if signal to noise ratio in the patterns is improved by simple integration. The method allows maps of local stress and dislocation density distributions to be generated in parallel with information concerning grain orientation, grain boundary misorientation and the presence of other microstructural features. The method is illustrated by example maps from a Ni-based superalloy and deformed Cu

  16. Heat Strain in Personal Protective Clothing: Challenges and Intervention Strategies

    Science.gov (United States)

    McLellan, T. M.; Daanen, H. A. M.

    Humans rely on sweat evaporation during exercise in the heat to promote cooling and to maintain thermal homeostasis. In protective clothing, however, sweat evaporation is severely hampered and this may lead to uncompensable heat strain, where core body temperature continues to rise leading to physical exhaustion and the cessation of work. The tolerance time depends on three main factors: (1) the initial core temperature that may be reduced by heat acclimation and pre-cooling, (2) the final core temperature, which can be increased due to physical training, and (3) the rate of change in body core temperature, which is dependent on the thermal environment, work rate and individual factors like body composition. Methods to reduce heat strain in protective clothing include: (1) increasing clothing permeability for air, (2) adjusting pacing strategy, including work/rest schedules, (3) physical training, and (4) cooling interventions.

  17. RobOKoD: microbial strain design for (overproduction of target compounds

    Directory of Open Access Journals (Sweden)

    Natalie Jane Stanford

    2015-03-01

    Full Text Available Sustainable production of target compounds such as biofuels and high-value chemicals for pharmaceutical, agrochemical and chemical industries is becoming an increasing priority given their current dependency upon diminishing petrochemical resources. Designing these strains is difficult, with current methods focussing primarily on knocking-out genes, dismissing other vital steps of strain design including the overexpression and dampening of genes. The design predictions from current methods also do not translate well into successful strains in the laboratory. Here, we introduce RobOKoD (Robust, Overexpression, Knockout and Dampening, a method for predicting strain designs for overproduction of targets. The method uses flux variability analysis to profile each reaction within the system under differing production percentages of target-compound and biomass. Using these profiles, reactions are identified as potential knockout, overexpression, or dampening targets. The identified reactions are ranked according to their suitability, providing flexibility in strain design for users. The software was tested by designing a butanol-producing Escherichia coli strain, and was compared against the popular OptKnock and RobustKnock methods. RobOKoD shows favourable design predictions, when predictions from these methods are compared to a successful butanol-producing experimentally-validated strain. Overall RobOKoD provides users with rankings of predicted beneficial genetic interventions with which to support optimised strain design.

  18. An objective approach for Burkholderia pseudomallei strain selection as challenge material for medical countermeasures efficacy testing

    Directory of Open Access Journals (Sweden)

    Kristopher E. Van Zandt

    2012-09-01

    Full Text Available Burkholderia pseudomallei is the causative agent of melioidosis, a rare disease of biodefense concern with high mortality and extreme difficulty in treatment. No human vaccines are available that protect against B. pseudomallei infection, and with the current limitations of antibiotic treatment, the development of new preventative and therapeutic interventions is crucial. Although clinical trials could be used to test the efficacy of new medical countermeasures (MCMs, the high mortality rates associated with melioidosis raises significant ethical issues concerning treating individuals with new compounds with unknown efficacies. The US Food and Drug Administration (FDA has formulated a set of guidelines for the licensure of new MCMs to treat diseases in which it would be unethical to test the efficacy of these drugs in humans. The FDA Animal Rule 21 CFR 314 calls for consistent, well-characterized B. pseudomallei strains to be used as challenge material in animal models. In order to facilitate the efficacy testing of new MCMs for melioidosis using animal models, we intend to develop a well-characterized panel of strains for use. This panel will comprise of strains that were isolated from human cases, have a low passage history, are virulent in animal models, and are well characterized phenotypically and genotypically. We have reviewed published and unpublished data on various B. pseudomallei strains to establish an objective method for selecting the strains to be included in the panel of B. pseudomallei strains with attention to five categories: animal infection models, genetic characterization, clinical and passage history, and availability of the strain to the research community. We identified 109 strains with data in at least one of the five categories, scored each strain based on the gathered data and identified 6 strains as candidate for a B. pseudomallei strain panel.

  19. CHALLENGES FOR ADOPTING INFLATION TARGETING REGIME IN EGYPT

    OpenAIRE

    Awad, Ibrahim

    2013-01-01

    This study intends to investigate challenges facing the CBE for adopting IT regime. Through exploiting the experience of Czech Republic, Poland, and Brazil in the early days of their adopting IT the study underscores the following challenges; (i) A more active role to be played by the CBE is needed to convince decision-making circuits inside the government for the adoption of IT. (ii) The CBE should be factually independent. (iii) Coordination between monetary policy and fiscal policy should ...

  20. Decorating Nanoparticle Surface for Targeted Drug Delivery: Opportunities and Challenges

    OpenAIRE

    Zhiqiang Shen; Mu-Ping Nieh; Ying Li

    2016-01-01

    The size, shape, stiffness (composition) and surface properties of nanoparticles (NPs) have been recognized as key design parameters for NP-mediated drug delivery platforms. Among them, the surface functionalization of NPs is of great significance for targeted drug delivery. For instance, targeting moieties are covalently coated on the surface of NPs to improve their selectively and affinity to cancer cells. However, due to a broad range of possible choices of surface decorating molecules, it...

  1. Mechanical Strains Induced in Osteoblasts by Use of Point Femtosecond Laser Targeting

    Directory of Open Access Journals (Sweden)

    Charles Cranfield

    2006-01-01

    Full Text Available A study demonstrating how ultrafast laser radiation stimulates osteoblasts is presented. The study employed a custom made optical system that allowed for simultaneous confocal cell imaging and targeted femtosecond pulse laser irradiation. When femtosecond laser light was focused onto a single cell, a rise in intracellular Ca2+ levels was observed followed by contraction of the targeted cell. This contraction caused deformation of neighbouring cells leading to a heterogeneous strain field throughout the monolayer. Quantification of the strain fields in the monolayer using digital image correlation revealed local strains much higher than threshold values typically reported to stimulate extracellular bone matrix production in vitro. This use of point targeting with femtosecond pulse lasers could provide a new method for stimulating cell activity in orthopaedic tissue engineering.

  2. Clinical Challenges to Current Molecularly Targeted Therapies in Lung Cancer

    Science.gov (United States)

    Chhabra, Gagan; Eggert, Ashley; Puri, Neelu

    2016-01-01

    Lung cancer is difficult to treat with a poor prognosis and a five year survival of 15%. Current molecularly targeted therapies are initially effective in non-small cell lung cancer (NSCLC) patients; however, they are plagued with difficulties including induced resistance and small therapeutically responsive populations. This mini review describes the mechanism of resistance to several molecularly targeted therapies which are currently being used to treat NSCLC. The major targets discussed are c-Met, EGFR, HER2, ALK, VEGFR, and BRAF. The first generation tyrosine kinase inhibitors (TKIs) resulted in resistance; however, second and third generation TKIs are being developed, which are generally more efficacious and have potential to treat NSCLC patients with resistance to first generation TKIs. Combination therapies could also be effective in preventing TKI resistance in NSCLC patients.

  3. Decorating Nanoparticle Surface for Targeted Drug Delivery: Opportunities and Challenges

    Directory of Open Access Journals (Sweden)

    Zhiqiang Shen

    2016-03-01

    Full Text Available The size, shape, stiffness (composition and surface properties of nanoparticles (NPs have been recognized as key design parameters for NP-mediated drug delivery platforms. Among them, the surface functionalization of NPs is of great significance for targeted drug delivery. For instance, targeting moieties are covalently coated on the surface of NPs to improve their selectively and affinity to cancer cells. However, due to a broad range of possible choices of surface decorating molecules, it is difficult to choose the proper one for targeted functions. In this work, we will review several representative experimental and computational studies in selecting the proper surface functional groups. Experimental studies reveal that: (1 the NPs with surface decorated amphiphilic polymers can enter the cell interior through penetrating pathway; (2 the NPs with tunable stiffness and identical surface chemistry can be selectively accepted by the diseased cells according to their stiffness; and (3 the NPs grafted with pH-responsive polymers can be accepted or rejected by the cells due to the local pH environment. In addition, we show that computer simulations could be useful to understand the detailed physical mechanisms behind these phenomena and guide the design of next-generation NP-based drug carriers with high selectivity, affinity, and low toxicity. For example, the detailed free energy analysis and molecular dynamics simulation reveals that amphiphilic polymer-decorated NPs can penetrate into the cell membrane through the “snorkeling” mechanism, by maximizing the interaction energy between the hydrophobic ligands and lipid tails. We anticipate that this work will inspire future studies in the design of environment-responsive NPs for targeted drug delivery.

  4. Therapies targeting cancer stem cells: Current trends and future challenges

    Institute of Scientific and Technical Information of China (English)

    Denisa; L; Dragu; Laura; G; Necula; Coralia; Bleotu; Carmen; C; Diaconu; Mihaela; Chivu-Economescu

    2015-01-01

    Traditional therapies against cancer, chemo- and radiotherapy, have multiple limitations that lead to treatment failure and cancer recurrence. These limitations are related to systemic and local toxicity, while treatment failure and cancer relapse are due to drug resistance and self-renewal, properties of a small population of tumor cells called cancer stem cells(CSCs). These cells are involved in cancer initiation, maintenance, metastasis and recurrence. Therefore, in order to develop efficient treatments that can induce a longlasting clinical response preventing tumor relapse it is important to develop drugs that can specifically target and eliminate CSCs. Recent identification of surface markers and understanding of molecular feature associated with CSC phenotype helped with the design of effective treatments. In this review we discuss targeting surface biomarkers, signaling pathways that regulate CSCs self-renewal and differentiation, drug-efflux pumps involved in apoptosis resistance, microenvironmental signals that sustain CSCs growth, manipulation of mi RNA expression, and induction of CSCs apoptosis and differentiation, with specific aim to hamper CSCs regeneration and cancer relapse. Some of these agents are under evaluation in preclinical and clinical studies, most of them for using in combination with traditional therapies. The combined therapy using conventional anticancer drugs with CSCs-targeting agents, may offer a promising strategy for management and eradication of different types of cancers.

  5. Genome Sequence of Klebsiella pneumoniae Ecl8, a Reference Strain for Targeted Genetic Manipulation

    OpenAIRE

    Fookes, Maria; Yu, Jing; De Majumdar, Shyamasree; Thomson, Nicholas; Schneiders, Thamarai

    2013-01-01

    We report the genome sequence of Klebsiella pneumoniae subsp. pneumoniae Ecl8, a spontaneous streptomycin-resistant mutant of strain ECL4, derived from NCIB 418. K. pneumoniae Ecl8 has been shown to be genetically tractable for targeted gene deletion strategies and so provides a platform for in-depth analyses of this species.

  6. The influence of angle of insonation and target depth on speckle-tracking strain

    DEFF Research Database (Denmark)

    Forsha, Daniel; Risum, Niels; Rajagopal, Sudarshan;

    2015-01-01

    BACKGROUND: Speckle-tracking strain is almost universally cited as being independent of angle of insonation, but there are minimal confirmatory studies, and this claim may not be consistent with the known limitations of ultrasound axial and lateral spatial resolution. The aim of this study was to...... strain analysis. Interangle reproducibility was significantly decreased compared with intraobserver reproducibility in the septal single-window comparison. Target depth assessment demonstrated a systematic bias between the near-field and far-field segments. CONCLUSIONS: Echocardiographically derived LPS...

  7. Controlling antimicrobial resistance through targeted, vaccine-induced replacement of strains.

    Directory of Open Access Journals (Sweden)

    Yonas I Tekle

    Full Text Available Vaccination has proven effective in controlling many infectious diseases. However, differential effectiveness with regard to pathogen genotype is a frequent reason for failures in vaccine development. Often, insufficient immune response is induced to prevent infection by the diversity of existing serotypes present in pathogenic populations of bacteria. These vaccines that target a too narrow spectrum of serotypes do not offer sufficient prevention of infections, and can also lead to undesirable strain replacements. Here, we examine a novel idea to specifically exploit the narrow spectrum coverage of some vaccines to combat specific, emerging multi- and pan-resistant strains of pathogens. Application of a narrow-spectrum vaccine could serve to prevent infections by some strains that are hard to treat, rather than offer the vaccinated individual protection against infections by the pathogenic species as such. We suggest that vaccines targeted to resistant serotypes have the potential to become important public health tools, and would represent a new approach toward reducing the burden of particular multi-resistant strains occurring in hospitals. Vaccines targeting drug-resistant serotypes would also be the first clinical intervention with the potential to drive the evolution of pathogenic populations toward drug-sensitivity. We illustrate the feasibility of this approach by modeling a hypothetical vaccine that targets a subset of methicillin-resistant Staphylococcus aureus (MRSA genotypes, in combination with drug treatment targeted at drug-sensitive genotypes. We find that a combined intervention strategy can limit nosocomial outbreaks, even when vaccine efficacy is imperfect. The broader utility of vaccine-based resistance control strategies should be further explored taking into account population structure, and the resistance and transmission patterns of the pathogen considered.

  8. Therapeutic challenges for systemic sclerosis: facts and future targets.

    Science.gov (United States)

    Cerinic Matucci, M; Del Rosso, Angela; Federico, Perfetto; Livi, Riccardo; Fiori, Ginevra; Bartoli, Francesca; Blagojevic, Jelena; Tempestini, Alessio; Pignone, Alberto

    2007-09-01

    Pulmonary arterial hypertension (PAH) is an important cause of death in systemic sclerosis (SSc), despite the improvement of therapies. An early diagnosis and the use of drugs interfering with the main pathogenic pathways of PAH is pivotal for the improvement of prognosis in primary PAH and PAH secondary to autoimmune rheumatic diseases, mainly SSc. Lately, new specific therapies have been developed targeting prostacyclin, endothelin, and nitric oxide pathways, the major pathogenic pathways leading to endothelial dysfunction in PAH. Epoprostenol improved life expectancy of patients with primary and secondary PAH, but its continuous intravenous administration requires experienced centers. More stable analogues of prostacyclin, administrated by intravenous (iloprost, treprostinil), subcutaneous, inhalatory (treprostinil, iloprost), and oral route (Beraprost) have shown efficacy in PAH. Bosentan, the first oral endothelin receptor antagonist (with affinity for endothelin A and B receptors) improves exercise function and survival in PAH, both primary and secondary to autoimmune rheumatic diseases. This is confirmed also for Sitaxsentan and Ambrisentan, selective A receptor antagonists. Because of its short half-life and systemic side effects, short-term NO inhalation is used only in short-term management of PAH in critically ill adults. Inhibitors of NO degradation, such as sildenafil, a phosphodiesterase (PDE) type 5 inhibitor, improved functional and hemodynamic parameters without significant side effects. Vardenafil and taladafil, longer-acting PDE inhibitors, also have vascular pulmonary selectivity. All these drugs may be used in combination, to maximize their clinical benefit not only in patients unresponsive to single drugs, but also potentially as initial therapy of PAH. PMID:17911460

  9. Identification of potential drug targets in Helicobacter pylori strain HPAG1 by in silico genome analysis.

    Science.gov (United States)

    Neelapu, Nageswara R R; Mutha, Naresh V R; Akula, Srinivas

    2015-01-01

    Helicobacter pylori colonizes the stomach, causing gastritis, peptic ulcers and gastric carcinoma. Drugs for treatment of H. pylori relieve from gastritis or pain but are not specific to H. pylori. Therefore, there is an immediate requirement for new therapeutic molecules to treat H. pylori. Current study investigates identification of drug targets in the strain HPAG1 of H. pylori by in silico genome analysis. Genome of HPAG1 was reconstructed for metabolic pathways and compared with Homosapien sapiens to identify genes which are unique to H. pylori. These unique genes were subjected to gene property analysis to identify the potentiality of the drug targets. Among the total number of genes analysed in H. pylori strain HPAG1, nearly 542 genes qualified as unique molecules and among them 29 were identified to be potential drug targets. Co/Zn/Cd efflux system membrane fusion protein, Ferric sidephore transport system and biopolymer transport protein EXbB were found to be critical drug targets to H. pylori HPAG1. Five genes (superoxide dismutase, HtrA protease/chaperone protein, Heatinducible transcription repressor HrcA, HspR, transcriptional repressor of DnaK operon, Cobalt-zinccadmium resistance protein CzcA) of the 29 predicted drug targets are already experimentally validated either genetically or biochemically lending credence to our unique approach. PMID:26205802

  10. Complex adenovirus-vectored vaccine protects guinea pigs from three strains of Marburg virus challenges

    International Nuclear Information System (INIS)

    The Marburg virus (MARV), an African filovirus closely related to the Ebola virus, causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, treatment of disease is only supportive, and no vaccines are available to prevent spread of MARV infections. In order to address this need, we have developed and characterized a novel recombinant vaccine that utilizes a single complex adenovirus-vectored vaccine (cAdVax) to overexpress a MARV glycoprotein (GP) fusion protein derived from the Musoke and Ci67 strains of MARV. Vaccination with the cAdVaxM(fus) vaccine led to efficient production of MARV-specific antibodies in both mice and guinea pigs. Significantly, guinea pigs vaccinated with at least 5 x 107 pfu of cAdVaxM(fus) vaccine were 100% protected against lethal challenges by the Musoke, Ci67 and Ravn strains of MARV, making it a vaccine with trivalent protective efficacy. Therefore, the cAdVaxM(fus) vaccine serves as a promising vaccine candidate to prevent and contain multi-strain infections by MARV

  11. Prolonged depression-like behavior caused by immune challenge: influence of mouse strain and social environment.

    Directory of Open Access Journals (Sweden)

    Evelin Painsipp

    Full Text Available Immune challenge by bacterial lipopolysaccharide (LPS causes short-term behavioral changes indicative of depression. The present study sought to explore whether LPS is able to induce long-term changes in depression-related behavior and whether such an effect depends on mouse strain and social context. LPS (0.83 mg/kg or vehicle was administered intraperitoneally to female CD1 and C57BL/6 mice that were housed singly or in groups of 4. Depression-like behavior was assessed with the forced swim test (FST 1 and 28 days post-treatment. Group-housed CD1 mice exhibited depression-like behavior 1 day post-LPS, an effect that leveled off during the subsequent 28 days, while the behavior of singly housed CD1 mice was little affected. In contrast, singly housed C57BL/6 mice responded to LPS with an increase in depression-like behavior that was maintained for 4 weeks post-treatment and confirmed by the sucrose preference test. Group-housed C57BL/6 mice likewise displayed an increased depression-like behavior 4 weeks post-treatment. The behavioral changes induced by LPS in C57BL/6 mice were associated with a particularly pronounced rise of interleukin-6 in blood plasma within 1 day post-treatment and with changes in the dynamics of the corticosterone response to the FST. The current data demonstrate that immune challenge with LPS is able to induce prolonged depression-like behavior, an effect that depends on genetic background (strain. The discovery of an experimental model of long-term depression-like behavior after acute immune challenge is of relevance to the analysis of the epigenetic and pathophysiologic mechanisms of immune system-related affective disorders.

  12. Addressing challenges in preparation of 211At-labeled biomolecules for use in targeted alpha therapy

    International Nuclear Information System (INIS)

    There are significant challenges in the development of 211At-labeled biomolecules for application to targeted alpha therapy. Challenges that we have addressed include development of: (1) labeling methods to obtain high in vivo 211At-label stability, (2) approaches to consistently obtain high recovery yields of Na[211At]At from irradiated bismuth targets, (3) methods to optimize biomolecule labeling yields, (4) reagents for use of 211At in pretargeting approach to cancer therapy, and (5) 211At-labeled antibodies in conditioning for hematopoietic cell transplantation. (author)

  13. Effects of challenge with a virulent genotype II strain of porcine reproductive and respiratory syndrome virus on piglets vaccinated with an attenuated genotype I strain vaccine.

    Science.gov (United States)

    Roca, M; Gimeno, M; Bruguera, S; Segalés, J; Díaz, I; Galindo-Cardiel, I J; Martínez, E; Darwich, L; Fang, Y; Maldonado, J; March, R; Mateu, E

    2012-07-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is endemic in most parts of Asia, where genotype I and II strains of diverse virulence may coexist. This study evaluated the outcome of infection with a highly virulent Asian genotype II PRRSV isolate in piglets vaccinated with a genotype I vaccine. Twenty-one 3-week-old piglets were divided in three groups: Pigs in group V (n=8) were vaccinated with an attenuated genotype I commercial PRRSV vaccine, while pigs in group U (n=8) and a control group (group C; n=5) were unvaccinated; 6 weeks later, pigs in groups V and U were challenged intranasally with a highly virulent strain of genotype II PRRSV (1×10(5) 50% tissue culture infectious doses/mL), while pigs in group C received a placebo. Over a period of 21 days after challenge, vaccinated pigs had significantly lower mortality (0/8 versus 2/8), fewer days of fever, a lower frequency of catarrhal bronchopneumonia, higher weight gains (13.4 versus 6.6 kg) and lower levels of viraemia compared to unvaccinated challenged pigs. Immunisation with a genotype I attenuated PRRSV vaccine provided partial protection against challenge with a highly virulent genotype II strain. PMID:22264642

  14. Cofactor modification analysis: a computational framework to identify cofactor specificity engineering targets for strain improvement.

    Science.gov (United States)

    Lakshmanan, Meiyappan; Chung, Bevan Kai-Sheng; Liu, Chengcheng; Kim, Seon-Won; Lee, Dong-Yup

    2013-12-01

    Cofactors, such as NAD(H) and NADP(H), play important roles in energy transfer within the cells by providing the necessary redox carriers for a myriad of metabolic reactions, both anabolic and catabolic. Thus, it is crucial to establish the overall cellular redox balance for achieving the desired cellular physiology. Of several methods to manipulate the intracellular cofactor regeneration rates, altering the cofactor specificity of a particular enzyme is a promising one. However, the identification of relevant enzyme targets for such cofactor specificity engineering (CSE) is often very difficult and labor intensive. Therefore, it is necessary to develop more systematic approaches to find the cofactor engineering targets for strain improvement. Presented herein is a novel mathematical framework, cofactor modification analysis (CMA), developed based on the well-established constraints-based flux analysis, for the systematic identification of suitable CSE targets while exploring the global metabolic effects. The CMA algorithm was applied to E. coli using its genome-scale metabolic model, iJO1366, thereby identifying the growth-coupled cofactor engineering targets for overproducing four of its native products: acetate, formate, ethanol, and lactate, and three non-native products: 1-butanol, 1,4-butanediol, and 1,3-propanediol. Notably, among several target candidates for cofactor engineering, glyceraldehyde-3-phosphate dehydrogenase (GAPD) is the most promising enzyme; its cofactor modification enhanced both the desired product and biomass yields significantly. Finally, given the identified target, we further discussed potential mutational strategies for modifying cofactor specificity of GAPD in E. coli as suggested by in silico protein docking experiments. PMID:24372035

  15. Correlates of Immune Protection in Chickens Vaccinated with Mycoplasma gallisepticum Strain GT5 following Challenge with Pathogenic M. gallisepticum Strain Rlow

    OpenAIRE

    Javed, Mohammed A.; Frasca, Salvatore; Rood, Debra; Cecchini, Katharine; Gladd, Martha; Geary, Steven J.; Silbart, Lawrence K.

    2005-01-01

    Colonization of the avian respiratory tract with Mycoplasma gallisepticum results in a profound inflammatory response in the trachea, air sacs, conjunctiva, and lungs. A live attenuated M. gallisepticum vaccine strain, GT5, was previously shown to be protective in chickens upon challenge; however, the mechanisms by which this vaccine and others confer protection remain largely unknown. The current study evaluated several potential correlates of GT5 vaccine-mediated immune protection following...

  16. Comparison of abortion and infection after experimental challenge of pregnant bison and cattle with Brucella abortus strain 2308

    Science.gov (United States)

    A comparative study was conducted using data from naive bison (n=45) and cattle (n=46) from 8 and 6 studies, respectively, in which a standardized Brucella abortus strain 2308 experimental challenge was administered. The incidence of abortion, fetal infection, uterine or mammary infection, or infec...

  17. Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Feng Jiang

    2015-10-01

    Full Text Available Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX, are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.

  18. Age-related effects of increasing postural challenge on eye movement onset latencies to visual targets.

    Science.gov (United States)

    Jimenez, Sergio; Hollands, Mark; Palmisano, Stephen; Kim, Juno; Markoulli, Maria; McAndrew, Darryl; Stamenkovic, Alexander; Walsh, Joel; Bos, Sophie; Stapley, Paul J

    2016-06-01

    When a single light cue is given in the visual field, our eyes orient towards it with an average latency of 200 ms. If a second cue is presented at or around the time of the response to the first, a secondary eye movement occurs that represents a reorientation to the new target. While studies have shown that eye movement latencies to 'single-step' targets may or may not be lengthened with age, secondary eye movements (during 'double-step' displacements) are significantly delayed with increasing age. The aim of this study was to investigate whether the postural challenge posed simply by standing (as opposed to sitting) results in significantly longer eye movement latencies in older adults compared to the young. Ten young (65 years) participated in the study. They were required to fixate upon a central target and move their eyes in response to 2 types of stimuli: (1) a single-step perturbation of target position either 15° to the right or left and (2) a double-step target displacement incorporating an initial target jump to the right or left by 15°, followed after 200 ms, by a shift of target position to the opposite side (e.g. +15° then -15°). All target displacement conditions were executed in sit and stand positions with the participant at the same distance from the targets. Eye movements were recorded using electro-oculography. Older adults did not show significantly longer eye movement latencies than the younger adults for single-step target displacements, and postural configuration (stand compared to sit) had no effect upon latencies for either group. We categorised double-step trials into those during which the second light changed after or before the onset of the eye shift to the first light. For the former category, young participants showed faster secondary eye shifts to the second light in the standing position, while the older adults did not. For the latter category of double-step trial, young participants showed no significant difference between

  19. Targeting cancer testis antigens for biomarkers and immunotherapy in colorectal cancer: Current status and challenges

    Institute of Scientific and Technical Information of China (English)

    Anil; Suri; Nirmala; Jagadish; Shikha; Saini; Namita; Gupta

    2015-01-01

    Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor asso-ciated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens have emerged as a potential targets for developing novel clinical biomarkers and immunotherapy for various malignancies. These germ cell specific proteins exhibit aberrant expression in cancer cells and contribute in tumorigenesis. Owing to their unique expression profile and immunogenicity in cancer patients, cancer testis antigens are clinically referred as the most promising tumor associated antigens. Several cancer testis antigens have been studied in colorectal cancer but none of them could be used in clinical practice. This review is an attempt to address the promising cancer testis antigens in colorectal cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions.

  20. Non-targeted effects of ionising radiation - A challenge to the current radiobiological paradigm

    International Nuclear Information System (INIS)

    A basic paradigm in radiobiology is that, after exposure to ionising radiation, the deposition of energy in the cell nucleus and the resulting damage to DNA, the primary target, are responsible for the harmful biological effects of radiation. The radiation-induced changes are thought to be fixed already in the first cell division following the radiation exposure and health effects are considered to result as a consequence of clonal proliferation of cells carrying mutations in specific genes. Since the initial damage induced in DNA has been shown to be directly proportional to dose, risk is also considered to be directly proportional to dose. Risk from multiple exposures is considered to be additive, and risk from high and low LET radiation exposure is assumed to be qualitatively the same. These assumptions are incorporated into the Linear-No-Threshold (LNT) Hypothesis that is used in all radiation protection practices. A range of evidence has now emerged that challenges the universality of the target theory of radiation induced effects. These effects have also been termed 'non-(DNA)-targeted' and include radiation-induced bystander effects, genomic instability, adaptive response, low-dose hyper-radiosensitivity, abscopal (out-of-field) effects of radiotherapy, clastogenic factors, delayed reproductive death and induction of genes by radiation. Essential features of non-targeted effects are that they do not require direct nuclear exposure by radiation and they are particularly significant at low doses. This new evidence suggests a need for a new paradigm in radiation biology. The new paradigm should cover both the classical (targeted) and the non-targeted effects. New aspects include the role of cellular communication and tissue-level responses. A better understanding of non-targeted effects may have important consequences on the health risk assessment and, consequently, on radiation protection. The non-targeted effects may contribute to the estimation of cancer

  1. Campylobacter jejuni strains of human and chicken origin are invasive in chickens after oral challenge

    DEFF Research Database (Denmark)

    Knudsen, Katrine Nørrelund; Bang, Dang Duong; Andresen, Lars Ole;

    2006-01-01

    The aim of the study was to evaluate the colonizing ability and the invasive capacity of selected Campylobacter jejuni strains of importance for the epidemiology of C jejuni in Danish broiler chickens. Four C jejuni strains were selected for experimental colonization Studies in day-old and 14-day......-old chickens hatched from specific pathogen free (SPF) eggs. Of the four C jejuni strains tested, three were Penner heat-stable serotype 2,flaA type 1/1, the most common type found among broilers and human cases in Denmark. The fourth strain was Penner heat-stable serotype 19, which has been shown to be...... associated with the Guillain Barre Syndrome (GBS) in humans. The minimum dose for establishing colonization in the clay-old chickens was approximately 2 cfu, whereas two- to threefold higher doses were required for establishing colonization in the 14-day-old chickens. Two of the C jejuni strains were shown...

  2. Anthrax Vaccine Antigen-Adjuvant Formulations Completely Protect New Zealand White Rabbits against Challenge with Bacillus anthracis Ames Strain Spores

    OpenAIRE

    Peachman, Kristina K.; Li, Qin; Matyas, Gary R.; Shivachandra, Sathish B.; Lovchik, Julie; Lyons, Rick C.; Alving, Carl R; Rao, Venigalla B.; Rao, Mangala

    2012-01-01

    In an effort to develop an improved anthrax vaccine that shows high potency, five different anthrax protective antigen (PA)-adjuvant vaccine formulations that were previously found to be efficacious in a nonhuman primate model were evaluated for their efficacy in a rabbit pulmonary challenge model using Bacillus anthracis Ames strain spores. The vaccine formulations include PA adsorbed to Alhydrogel, PA encapsulated in liposomes containing monophosphoryl lipid A, stable liposomal PA oil-in-wa...

  3. Pediatric Malignant Bone Tumors: A Review and Update on Current Challenges, and Emerging Drug Targets.

    Science.gov (United States)

    Jackson, Twana M; Bittman, Mark; Granowetter, Linda

    2016-07-01

    Osteosarcoma (OS) and the Ewing sarcoma family of tumors (ESFT) are the most common malignant bone tumors in children and adolescents. While significant improvements in survival have been seen in other pediatric malignancies the treatment and prognosis for pediatric bone tumors has remained unchanged for the past 3 decades. This review and update of pediatric malignant bone tumors will provide a general overview of osteosarcoma and the Ewing sarcoma family of tumors, discuss bone tumor genomics, current challenges, and emerging drug targets. PMID:27265835

  4. Strain-promoted copper free click chemistry for 64Cu radiolabeling of integrin-αvβ6 targeted peptide

    International Nuclear Information System (INIS)

    Strain promoted copper free click chemistry offers a fast and efficient method for preparation of radio labeled molecular probes and pre-targeted imaging in vivo. The fast reaction kinetics, driven by the release of strain energy ranging from 10-19 kcal/mol for cyclooctynes, precludes the need for toxic copper catalyst for chemical ligation between alkynes and azides. In particular this catalyst free approach provides a favorable platform for synthesis of radiometalated probes requiring macrocycle chelates for formation of stable and kinetically inert complexes where Cu(I) can interfere with metal chelates. In present studies DOTA-ADIBO (azadibenzocyclooctyne amine), a strained chelate-alkyne system has been constructed for bioconjugation with the azide-modified PEGylated peptide, N3-Ala-PEG28-A20FMDV2 and radiolabeled with (64Cu) Cu for assessment as a integrin-αvβ6, targeting molecular probe

  5. Effect of challenge of pigs previously immunised with inactivated vaccines containing homologous and heterologous Mycoplasma hyopneumoniae strains

    Directory of Open Access Journals (Sweden)

    Villarreal Iris

    2012-01-01

    Full Text Available Abstract Background Mycoplasma hyopneumoniae is the primary cause of enzootic pneumonia in pigs. Although vaccination is an important control tool, the results observed under field conditions are variable. This may be due to antigenic differences between the strains circulating in pig herds and the vaccine strain. This study compared the protective efficacy of four bacterins against challenge infection with a highly virulent field strain of M. hyopneumoniae. Seventy eight, one-week old piglets were randomly assigned to five treatment groups (A, B, C, D, E, 14 piglets each, and a negative control group (F consisting of 8 piglets. All pigs were injected at 1 (D7 and 4 weeks of age (D28, with 2 ml of either a placebo or a bacterin based on selected M. hyopneumoniae strains, namely A (F7.2C, B (F20.1L, C (B2V1W20 1A-F, D (J strain, E (placebo; positive control, F (placebo; negative control. At D56, all pigs except those of group F were challenged intratracheally with 7 ml culture medium containing 107 CCU/ml of M. hyopneumoniae strain F7.2C. All pigs were euthanized and necropsied at D84. The severity of coughing and pneumonia lesions were the main parameters. Immunofluorescence (IF testing, nested PCR testing of bronchoalveolar lavage (BAL fluid and serology for M. hyopneumoniae were also performed. Results The different bacterins only slightly improved clinical symptoms (average 0.38 in vaccinated groups vs. 0.45 in group E and histopathological lung lesions (average 3.20 in vaccinated groups vs. 3.45 in group E, but did not improve macroscopic lung lesions (score 4.30 vs. 4.03 in group E. None of the vaccines was significantly and/or consistently better or worse than the other ones. All bacterins evoked a serological response in the vaccinated animals. All pigs, except those from group F, were positive with nPCR in BAL fluid at D84. Conclusion The bacterins did not induce a clear overall protection against challenge infection, and there were no

  6. Oral vaccination with microencapsuled strain 19 vaccine confers enhanced protection against Brucella abortus strain 2308 challenge in red deer (Cervus elaphus elaphus).

    Science.gov (United States)

    Arenas-Gamboa, Angela M; Ficht, Thomas A; Davis, Donald S; Elzer, Philip H; Kahl-McDonagh, Melissa; Wong-Gonzalez, Alfredo; Rice-Ficht, Allison C

    2009-10-01

    Bison (Bison bison) and elk (Cervus elaphus nelsoni) in the Greater Yellowstone Area (GYA), USA, are infected with Brucella abortus, the causative agent of bovine brucellosis, and they serve as a wildlife reservoir for the disease. Bovine brucellosis recently has been transmitted from infected elk to cattle in Montana, Wyoming, and Idaho and has resulted in their loss of brucellosis-free status. An efficacious Brucella vaccine with a delivery system suitable for wildlife would be a valuable tool in a disease prevention and control program. We evaluated Strain 19 (S19) in a sustained release vehicle consisting of alginate microspheres containing live vaccine. In a challenge study using red deer (Cervus elaphus elaphus) as a model for elk, alginate, a naturally occurring polymer combined with a protein of Fasciola hepatica vitelline protein B was used to microencapsulate S19. Red deer were orally or subcutaneously immunized with 1.5 x 10(10) colony-forming units (CFUs) using microencapsulated S19. Humoral and cellular profiles were analyzed bimonthly throughout the study. The vaccinated red deer and nonvaccinated controls were challenged 1 yr postimmunization conjunctivally with 1 x 10(9) CFUs of B. abortus strain 2308. Red deer vaccinated with oral microencapsulated S19 had a statistically significant lower bacterial tissue load compared with controls. These data indicate for the first time that protection against Brucella-challenge can be achieved by combining a commonly used vaccine with a novel oral delivery system such as alginate-vitelline protein B microencapsulation. This system is a potential improvement for efficacious Brucella-vaccine delivery to wildlife in the GYA. PMID:19901378

  7. Challenges and limitations of targeting cancer stem cells and/or the tumour microenvironment

    Directory of Open Access Journals (Sweden)

    Juan Sebastian Yakisich

    2012-05-01

    Full Text Available The existence of cancer cells with stem cell properties (Cancer Stem Cells, CSCs and their association with tumor resistance and relapse has led to the search for active compounds to eliminate these cells or modulate their stemness in the hope of curing cancer. So far, three classes of drugs that target cancer stemness (Stemness Modulator Drugs have been identified: i drugs that selectively eliminate CSCs (stem cell targeting drugs; ii drugs that decrease stemness (stemness inhibitor drugs; and iii drugs that promote stemness (stemness promoting drugs. In addition, microenvironment modulating drugs aimed at selectively targeting the stem cell niche are being investigated and may represent an important class of drug for cancer therapy. This article will briefly review the current use of these substances and discuss the potential outcomes, challenges and limitations of treatment modalities using these classes of drugs for cancer treatment. Finally, a modular tumor model will be proposed as a guide to integrate our knowledge on the biology of cancer stem cell with that of the tumor microenvironment to promote a more rational development of anticancer therapy.

  8. Campylobacter jejuni strains of human and chicken origin are invasive in chickens after oral challenge

    DEFF Research Database (Denmark)

    Knudsen, Katrine Nørrelund; Bang, Dang Duong; Andresen, Lars Ole; Madsen, Mogens

    2006-01-01

    associated with the Guillain Barre Syndrome (GBS) in humans. The minimum dose for establishing colonization in the clay-old chickens was approximately 2 cfu, whereas two- to threefold higher doses were required for establishing colonization in the 14-day-old chickens. Two of the C jejuni strains were shown...

  9. Nontoxigenic Clostridium difficile Protects Hamsters against Challenge with Historic and Epidemic Strains of Toxigenic BI/NAP1/027 C. difficile

    OpenAIRE

    Nagaro, Kristin J.; Phillips, S. Tyler; Cheknis, Adam K.; Sambol, Susan P.; Zukowski, Walter E.; Johnson, Stuart; Gerding, Dale N.

    2013-01-01

    Nontoxigenic Clostridium difficile (NTCD) has been shown to prevent fatal C. difficile infection in the hamster model when hamsters are challenged with standard toxigenic C. difficile strains. The purpose of this study was to determine if NTCD can prevent C. difficile infection in the hamster model when hamsters are challenged with restriction endonuclease analysis group BI C. difficile strains. Groups of 10 hamsters were given oral clindamycin, followed on day 2 by 106 CFU of spores of NTCD ...

  10. Production of Monoclonal Antibodies Against the Challenge Strain of Infectious Laryngotracheitis Virus of Chickens and Their Use in an Indirect Immunofluorescent Diagnostic Test

    OpenAIRE

    Ferhat Abbas*, James Andreasen1, Rockey Becker1, Masroor Ahmed, M Arif Awan, Abdul Wadood and Anita Sonn1

    2010-01-01

    The objective of the present research was to produce monoclonal antibodies (MCAs) against the USDA challenge strain of infectious laryngotracheitis virus and to perform an initial investigation of their use in an indirect immunofluorescence diagnostic test. Fourteen-day old chicken embryo liver cells were grown in tissue culture plates. Confluent monolayers were obtained after 48 hours. Monolayers were infected with the USDA challenge strain of infectious laryngotracheitis virus (ILTV). Cytop...

  11. Immune responses of different mouse strains after challenge with equivalent lethal doses of toxoplasma Gondii

    Directory of Open Access Journals (Sweden)

    Lee Y.H.

    2004-03-01

    Full Text Available Most immunological studies that utilize different strains of inbred mice following T. gondii infection fail to compensate for differences in host susceptibility to the size of the parasite innoculum. To address this concern, susceptible C57BL/6 and resistant CBA/J mice were orally infected with either an equivalent 50 % lethal dose (LD50 of brain cysts of the 76K strain of T. gondii (15 cysts in C57BL/6, 400 cysts in CBA/J or the same dose of parasites in each mouse strain. C57BL/6 mice receiving 400 cysts (LD50 of CBA/J mice died post infection, whereas CBA/J mice that received 15 cysts (LD50 of C57BL/6 mice survived. Parasite loads in the brains and serum Toxoplasma specific lgG1 titers of LD50-infected C57BL/6 mice were significantly higher than those in LD50- or 15 cysts-infected CBA/J mice, whereas splenocyte proliferation to Toxoplasma antigen and the percentage of CD8α+T cells were reduced in LD50-infected C57BL/6 mice. In contrast, serum lgG2a and lgM titers, the percentage of γδ T cells and IFN-γ expression of spleen of LD50- infected CBA/J mice were higher than those of either 15 cysts- infected CBA/J mice or LD50-infected C57BL/6 mice. These observations demonstrate that the immune response between LD50- infected C57BL/6 and CBA/J mice was more prominent when compared to C57BL/6 or CBA/J mice receiving the same parasite inoculum. These observations would suggest that caution must be excersized in the planning and interpretation of data when the size of the parasite inoculum has not been adjusted for mouse strain.

  12. Mangiferin, an Anti-HIV-1 Agent Targeting Protease and Effective against Resistant Strains

    OpenAIRE

    Rui-Rui Wang; Yue-Dong Gao; Chun-Hui Ma; Xing-Jie Zhang; Cheng-Gang Huang; Jing-Fei Huang; Yong-Tang Zheng

    2011-01-01

    The anti-HIV-1 activity of mangiferin was evaluated. Mangiferin can inhibit HIV-1ⅢB induced syncytium formation at non-cytotoxic concentrations, with a 50% effective concentration (EC50) at 16.90 μM and a therapeutic index (TI) above 140. Mangiferin also showed good activities in other laboratory-derived strains, clinically isolated strains and resistant HIV-1 strains. Mechanism studies revealed that mangiferin might inhibit the HIV-1 protease, but is still effective against HIV peptidic prot...

  13. Protection against lethal subcutaneous challenge of virulent Y. pestis strain 141 using an F1-V subunit vaccine

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In this study, we designed and engineered a two-component recombinant fusion protein antigen as a vaccine candidate against the possible biological threat of Yersinia pestis. The recombinant F1-V protein was formulated with Alhydrogel. A four-time injection with a dosage of 10, 20 and 50 μg/mouse in about two months was adopted for vaccination. Serum antibodies and subclass of T helper cells were measured and analyzed. After the final vaccination, the mice were challenged by 141 strain with 25―600 LD50. In conclusion, the recombinant vaccine was capable of inducing protective immunity against subcutaneous challenge. The level of serum IgG was supposed to be a main factor that affected the final protection of challenge. 20 μg recombinant protein could induce an endpoint titre of serum IgG as high as 51200, which was enough to afford 100% protection against 400 LD50 virulent 141 challenge. The antibody isotype analysis showed that the vaccine induced predominantly an IgG1 rather than IgG2a response. Flow cytometric analysis revealed that Alhydrogel significantly helped induce a stronger humoral immunity instead of CTL cellular response. These findings suggested that the plague F1-V subunit vaccine is promising for the next plague vaccine.

  14. Effect of different feed ingredients and additives on IPEC-J2 cells challenged with an enterotoxigenic Escherichia coli strain.

    Science.gov (United States)

    Spitzer, F; Speiser, S; Vahjen, W; Zentek, J

    2016-08-01

    The intestinal porcine epithelial cell line IPEC-J2 was used as an in vitro model to assess effects of additives on the adhesion and cell toxic effects of a F4-positive (ETEC) and a F4-negative Escherichia coli (DSM 2840) strain. Bacterial adhesion was examined using flow cytometry in IPEC-J2 cells infected with bacteria stained with 5,6-carboxymethyl fluorescein diacetate succinimidyl ester. Measurement of transepithelial electrical resistance (TEER) was performed to characterize the impact on IPEC-J2 monolayer integrity. The feed additives were prepared as aqueous extract and tested in different dilutions and incubation times. The F4-positive ETEC strain had a high adhesion to IPEC-J2 cells and reduced TEER shortly after the in vitro infection. The nonpathogenic E. coli strain DSM 2840 showed only low adhesion capacity and no TEER impairment. Infection with ETEC with added test extracts showed a reduction of bacterial adhesion to IPEC-J2 cells by an autolyzed yeast product (p mix did not interfere with the ETEC adherence. The TEER decrease of the IPEC-J2 monolayer after ETEC infection was not affected by the added substances. In conclusion, interference with epithelial adhesion might be a protective mechanism of the tested yeast extract, indicating that the cell culture model might be suitable as screening tool to complement in vivo challenge trials with piglets. PMID:26275434

  15. Brucella abortus S19 and RB51 vaccine immunogenicity test: Evaluation of three mice (BALB/c, Swiss and CD-1) and two challenge strains (544 and 2308).

    Science.gov (United States)

    Miranda, Karina Leite; Dorneles, Elaine Maria Seles; Pauletti, Rebeca Barbosa; Poester, Fernando Padilla; Lage, Andrey Pereira

    2015-01-15

    The aim of the present study was to evaluate the use of different mouse strains (BALB/c, Swiss and CD-1) and different challenge strains (Brucella abortus 544 and 2308) in the study of B. abortus vaccine (S19 and RB51) immunogenicity test in the murine model. No significant difference in B. abortus vaccine potency assay was found with the use of B. abortus 544 or B. abortus 2308 as challenge strain. Results of variance analysis showed an interaction between treatment and mouse strain; therefore these parameters could not be compared separately. When CD-1 groups were compared, those vaccinated showed significantly lower counts than non-vaccinated ones (PS19 or RB51). Similar results were observed on BALB/c groups. However, in Swiss mouse groups, S19 was more protective than RB51 (Pabortus strains 544 and 2308, can be used in immunogenicity tests of S19 and RB51 vaccines. PMID:25498211

  16. [Challenge to the Development of Molecular Targeted Therapy against a Novel Target Candidate Identified by Antibody Proteomics Technology].

    Science.gov (United States)

    Nagano, Kazuya

    2016-01-01

    Disease proteomics that systemically analyzes and identifies differentially expressed proteins between healthy and diseased samples is a potentially useful approach for obtaining target proteins for drug development. To date, however, very few target proteins have been identified from this field. A key issue that remains to be resolved is how to correctly identify target proteins from a number of potential candidates. To circumvent this problem, we have developed "antibody proteomics technology" in which a single chain Fv phage antibody library is utilized for proteome analysis. Here, we describe the application of this technology by primarily focusing on Eph receptor A10 (EphA10), a novel breast cancer-related protein that is a promising target for antibody drugs. To establish an effective and safe targeted cancer therapy, it is important that the target is specifically expressed in cancer tissues. Therefore, we attempted to analyze the EphA10 expression profiles. Tissue microarray analysis showed that EphA10 was expressed in all subtypes of breast cancer containing triple negative breast cancer cases. On the other hand, EphA10 was only expressed in testis tissue among 36 kinds of normal tissues. Thus, EphA10 could be a highly cancer-specific protein, making it a promising target for female breast cancer patients. Finally, we examined the anti-tumor effect by anti-EphA10 antibody, aiming for the development of a novel EphA10 targeting therapy. Administration of the antibody showed that tumor volumes were significantly inhibited. Our results suggest that targeting EphA10 in breast cancer cases might be a promising new form of therapy. PMID:26831784

  17. Challenges Surrounding the Injection and Arrival of Targets at LIFE Fusion Chamber Center

    Energy Technology Data Exchange (ETDEWEB)

    Miles, R; Spaeth, M; Manes, K; Amendt, P; Tabak, M; Bond, T; Kucheyev, S; Latkowski, J; Loosmore, G; Bliss, E; Baker, K; Bhandarkar, S; Petzoldt, R; Alexander, N; Tillack, M; Holdener, D

    2010-12-01

    IFE target designers must consider several engineering requirements in addition to the physics requirements for successful target implosion. These considerations include low target cost, high manufacturing throughput, the ability of the target to survive the injection into the fusion chamber and arrive in a condition and physical position consistent with proper laser-target interaction and ease of post-implosion debris removal. This article briefly describes these considerations for the Laser Inertial Fusion-based Energy (LIFE) targets currently being designed.

  18. Effect of Two Strains of Probiotics on the Antioxidant Capacity, Oxidative Stress, and Immune Responses of Salmonella-Challenged Broilers

    Directory of Open Access Journals (Sweden)

    AM Abudabos

    2016-03-01

    Full Text Available Abstract The present study aimed at evaluating the effect of two strains of probiotics (Bacillus subtilis PB6 and Bacillus Cereus var. toyoi on selected indicators of the antioxidant status and immune responses of broilers before and after challenge with Salmonella enterica subsp. Typhimurium (S. typhimurium. Birds were distributed into the following five treatments: negative control (CTL−; negative control+S. typhimurium (CTL+; antibiotic+S. typhimurium, (AB; Toyocerin(r+S. typhimurium (TOYO; and CloSTATTM+ S. typhimurium (CLOS. Birds in all treatments, except for CTL−, were orally challenged with 3 x109 CFUS. typhimurium at 16 days of age. The results showed that total antioxidant capacity (TAC, superoxide dismutase activity (SOD, and hydrogen peroxide (H2O2 values were similar among all groups. The antibody titers against S. typhimurium and Newcastle disease (ND were not affected by the treatments (p>0.05. However, S. typhimurium and ND titers were influenced by the interaction between week and treatment (p<0.01, p<0.05, respectively and by week (p<0.001, p<0.001, respectively. In conclusion, S. typhimurium challenge had an impact on anti-Salmonella and NC titers. Both probiotics did not affect the broilers' antioxidant capacity.

  19. Targeting thrombin long-term after an acute coronary syndrome: Opportunities and challenges.

    Science.gov (United States)

    De Caterina, Raffaele; Goto, Shinya

    2016-06-01

    Patients after an acute coronary syndrome (ACS) are at increased risk of recurrent thrombotic events, justifying the search for additional antithrombotic treatments. The pathophysiology of ACS involves arterial thrombus formation, in turn occurring because of a combination of platelet activation and fibrin formation, with thrombin playing a key role in both. Antiplatelet therapy, targeting the thromboxane pathway and the ADP P2Y12 receptor has been widely accepted for secondary prevention after an ACS. Now, data from recent clinical trials in such patients also encourage the pursuit of inhibiting thrombin formation or thrombin-mediated platelet activation in addition to antiplatelet therapy. This "triple pathway inhibition", including inhibition of thrombin activity or thrombin receptor(s), is currently an option in pure ACS, but already a must in the setting of ACS accompanied by atrial fibrillation (AF), where anticoagulants have been shown to be much more effective than antiplatelet agents in preventing stroke. We here discuss the challenges of managing combined thrombin activity or receptor inhibition and antiplatelet therapy in all such patients. Translating this into practice still requires further studies and patient tailoring to fully exploit its potential. PMID:26994821

  20. Targeted Gene Disruption of the Cyclo (L-Phe, L-Pro Biosynthetic Pathway in Streptomyces sp. US24 Strain

    Directory of Open Access Journals (Sweden)

    Samiha Sioud

    2007-01-01

    Full Text Available We have previously isolated a new actinomycete strain from Tunisian soil called Streptomyces sp. US24, and have shown that it produces two bioactive molecules including a Cyclo (L-Phe, L-Pro diketopiperazine (DKP. To identify the structural genes responsible for the synthesis of this DKP derivative, a PCR amplification (696 bp was carried out using the Streptomyces sp. US24 genomic DNA as template and two degenerate oligonucleotides designed by analogy with genes encoding peptide synthetases (NRPS. The detection of DKP derivative biosynthetic pathway of the Streptomyces sp. US24 strain was then achieved by gene disruption via homologous recombination using a suicide vector derived from the conjugative plasmid pSET152 and containing the PCR product. Chromatography analysis, biological tests and spectroscopic studies of supernatant cultures of the wild-type Streptomyces sp. US24 strain and three mutants obtained by this gene targeting disruption approach showed that the amplified DNA fragment is required for Cyclo (L-Phe, L-Pro biosynthesis in Streptomyces sp. US24 strain. This DKP derivative seems to be produced either directly via a nonribosomal pathway or as a side product in the course of nonribosomal synthesis of a longer peptide.

  1. Mangiferin, an Anti-HIV-1 Agent Targeting Protease and Effective against Resistant Strains

    Directory of Open Access Journals (Sweden)

    Rui-Rui Wang

    2011-05-01

    Full Text Available The anti-HIV-1 activity of mangiferin was evaluated. Mangiferin can inhibit HIV-1ⅢB induced syncytium formation at non-cytotoxic concentrations, with a 50% effective concentration (EC50 at 16.90 μM and a therapeutic index (TI above 140. Mangiferin also showed good activities in other laboratory-derived strains, clinically isolated strains and resistant HIV-1 strains. Mechanism studies revealed that mangiferin might inhibit the HIV-1 protease, but is still effective against HIV peptidic protease inhibitor resistant strains. A combination of docking and pharmacophore methods clarified possible binding modes of mangiferin in the HIV-1 protease. The pharmacophore model of mangiferin consists of two hydrogen bond donors and two hydrogen bond acceptors. Compared to pharmacophore features found in commercially available drugs, three pharmacophoric elements matched well and one novel pharmacophore element was observed. Moreover, molecular docking analysis demonstrated that the pharmacophoric elements play important roles in binding HIV-1 protease. Mangiferin is a novel nonpeptidic protease inhibitor with an original structure that represents an effective drug development strategy for combating drug resistance.

  2. Addressing the challenges for sustainable production of algal biofuels: I. Algal strains and nutrient supply.

    Science.gov (United States)

    Abdelaziz, Ahmed E M; Leite, Gustavo B; Hallenbeck, Patrick C

    2013-01-01

    Microalgae hold promise for the production of sustainable replacement of fossil fuels due to their high growth rates, ability to grow on non-arable land and their high content, under the proper conditions, of high energy compounds that can be relatively easily chemically converted to fuels using existing technology. However, projected large-scale algal production raises a number of sustainability concerns concerning land use, net energy return, water use and nutrient supply. The state-of-the-art of algal production of biofuels is presented with emphasis on some possible avenues to provide answers to the sustainability questions that have been raised. Here, issues concerning algal strains and supply of nutrients for large-scale production are discussed. Since sustainability concerns necessitate the use of wastewaters for supply of bulk nutrients, emphasis is placed on the composition and suitability of different wastewater streams. At the same time, algal cultivation has proven useful in waste treatment processes, and thus this aspect is also treated in some detail. PMID:24350435

  3. Identification of planctomycetes with order-, genus-, and strain-specific 16S rRNA-targeted probes.

    Science.gov (United States)

    Gade, D; Schlesner, H; Glöckner, F O; Amann, R; Pfeiffer, S; Thomm, M

    2004-04-01

    A specific 16S rRNA-targeted oligonucleotide probe (PIR1223) for the genus Pirellula and a species-specific probe (RB454) for Pirellula sp. strain SH1 have been designed and optimized. Together with the already existing order-specific probe PLA886, the two newly designed probes were used to detect and identify planctomycetes, pirellulae, and close relatives of Pirellula sp. strain SH1 in different habitats. With the help of these probes for detection and identification, bacteria of the genus Pirellula were detected and cultivated from tissue of the Mediterranean sponge Aplysina aerophoba and from the water column of the Kiel Fjord. An unexpected result was the close phylogenetic relationship of the isolate from the sponge and the brackish water habitat Kiel Fjord as revealed by DNA/DNA hybridization. PMID:14994173

  4. Targeting the PD1/PD-L1 axis in melanoma: Biological rationale, clinical challenges and opportunities

    OpenAIRE

    Barbara Merelli; Daniela Massi; Laura Cattaneo; Mario Mandalà

    2014-01-01

    In this review we summarize the biological role of PD-1/PD-L1 on cancer by focusing our attention in the biological rationale, clinical challenges and opportunities to target the PD-1/PD-L1 axis in melanoma.

  5. A monoclonal antibody targeting a highly conserved epitope in influenza B neuraminidase provides protection against drug resistant strains.

    Science.gov (United States)

    Doyle, Tracey M; Li, Changgui; Bucher, Doris J; Hashem, Anwar M; Van Domselaar, Gary; Wang, Junzhi; Farnsworth, Aaron; She, Yi-Min; Cyr, Terry; He, Runtao; Brown, Earl G; Hurt, Aeron C; Li, Xuguang

    2013-11-01

    All influenza viral neuraminidases (NA) of both type A and B viruses have only one universally conserved sequence located between amino acids 222-230. A monoclonal antibody against this region has been previously reported to provide broad inhibition against all nine subtypes of influenza A NA; yet its inhibitory effect against influenza B viral NA remained unknown. Here, we report that the monoclonal antibody provides a broad inhibition against various strains of influenza B viruses of both Victoria and Yamagata genetic lineage. Moreover, the growth and NA enzymatic activity of two drug resistant influenza B strains (E117D and D197E) are also inhibited by the antibody even though these two mutations are conformationally proximal to the universal epitope. Collectively, these data suggest that this unique, highly-conserved linear sequence in viral NA is exposed sufficiently to allow access by inhibitory antibody during the course of infection; it could represent a potential target for antiviral agents and vaccine-induced immune responses against diverse strains of type B influenza virus. PMID:24140051

  6. Challenge of pigs with classical swine fever viruses after C-strain vaccination reveals remarkably rapid protection and insights into early immunity.

    Directory of Open Access Journals (Sweden)

    Simon P Graham

    Full Text Available Pre-emptive culling is becoming increasingly questioned as a means of controlling animal diseases, including classical swine fever (CSF. This has prompted discussions on the use of emergency vaccination to control future CSF outbreaks in domestic pigs. Despite a long history of safe use in endemic areas, there is a paucity of data on aspects important to emergency strategies, such as how rapidly CSFV vaccines would protect against transmission, and if this protection is equivalent for all viral genotypes, including highly divergent genotype 3 strains. To evaluate these questions, pigs were vaccinated with the Riemser® C-strain vaccine at 1, 3 and 5 days prior to challenge with genotype 2.1 and 3.3 challenge strains. The vaccine provided equivalent protection against clinical disease caused by for the two challenge strains and, as expected, protection was complete at 5 days post-vaccination. Substantial protection was achieved after 3 days, which was sufficient to prevent transmission of the 3.3 strain to animals in direct contact. Even by one day post-vaccination approximately half the animals were partially protected, and were able to control the infection, indicating that a reduction of the infectious potential is achieved very rapidly after vaccination. There was a close temporal correlation between T cell IFN-γ responses and protection. Interestingly, compared to responses of animals challenged 5 days after vaccination, challenge of animals 3 or 1 days post-vaccination resulted in impaired vaccine-induced T cell responses. This, together with the failure to detect a T cell IFN-γ response in unprotected and unvaccinated animals, indicates that virulent CSFV can inhibit the potent antiviral host defences primed by C-strain in the early period post vaccination.

  7. Comparison Study on Clinical and Neuropathological Characteristics of Hamsters Inoculated With Scrapie Strain 263K in Different Challenging Pathways

    Institute of Scientific and Technical Information of China (English)

    JIN ZHANG; XIAO-BO ZHOU; GUI-PING MA; YONG LIU; CAI-MIN XU; XIAO-PING DONG; LAN CHEN; BAO-YUN ZHAN; JUN HAN; XIN-LI XIAO; HAI-YAN TIAN; BIN-LING LI; CHEN GAO; JIAN-MEI GAO

    2004-01-01

    Objective To understand the infectious characteristics of a hamster-adapted scrapie strain 263K with five different routes of infection including intracerebral (i.c.), intraperitoneal (i.p.),intragastrical (i.g.), intracardiac and intramuscular (i. m.) approaches. Methods Hamsters were infected with crude- or fine-prepared brain extracts. The neuropathological changes, PrPSc deposits,and patterns of PK-resistant PrP were analyzed by HE stain, immunohistochemistry (IHC) assay and Western blot. Reactive gliosis and neuron loss were evaluated by glial fibrillary acidic protein (GFAP)and neuron specific enolase (NSE) specific IHC. Results The animals inoculated in i.m. and i.p.ways with crude PrPSc extracts showed clinical signs at the average incubation of 69.2+-2.8 and 65.5±3.9 days. Inoculation in i.c. and intracardiac ways with fine PrPSc extracts (0.00035 g) caused similar,but relative long incubation of around 90 days. Only oneout of eight hamsters challenged ini.g way with low dosage (0.01 g) became ill after a much longer incubation (185 d), while all animals (4/4)with high dosage (0.04 g) developed clinical signs 105 days postinfection. The most remarkable spongiform degeneration and PrPsc deposits were found in brain stem among the five challenge groups generally. The number of GFAP-positive astrocytes increased distinctly in brain stems in all infection groups, while the number of NSE-positive cells decreased significantly in cerebrum, except i.c. group. The patterns of PK-resistant PrP in brains were basically identical among the five infection routes. Conclusion Typical TSE could be induced in hamsters by inoculating strain 263K in the five infection ways. The incubation periods in bioassays depend on infective dosage, administrating pathway and preparation of PrPSc. The neuropathological changes and PrPSc deposits seem to be related with regions and inoculating pathways.

  8. Developing a commercial production process for 500,000 targets per day: A key challenge for inertial fusion energy

    International Nuclear Information System (INIS)

    As is true for current-day commercial power plants, a reliable and economic fuel supply is essential for the viability of future Inertial Fusion Energy (IFE) [Energy From Inertial Fusion, edited by W. J. Hogan (International Atomic Energy Agency, Vienna, 1995)] power plants. While IFE power plants will utilize deuterium-tritium (DT) bred in-house as the fusion fuel, the 'target' is the vehicle by which the fuel is delivered to the reaction chamber. Thus the cost of the target becomes a critical issue in regard to fuel cost. Typically six targets per second, or about 500 000/day are required for a nominal 1000 MW(e) power plant. The electricity value within a typical target is about $3, allocating 10% for fuel cost gives only 30 cents per target as-delivered to the chamber center. Complicating this economic goal, the target supply has many significant technical challenge - fabricating the precision fuel-containing capsule, filling it with DT, cooling it to cryogenic temperatures, layering the DT into a uniform layer, characterizing the finished product, accelerating it to high velocity for injection into the chamber, and tracking the target to steer the driver beams to meet it with micron-precision at the chamber center

  9. Modelling the impacts of challenging 2020 non-ETS GHG emissions reduction targets on Ireland′s energy system

    International Nuclear Information System (INIS)

    This paper focuses on Ireland's ambitious target for 2020 to reduce greenhouse gas (GHG) emissions by 20% below 2005 levels for sectors not covered by ETS (Non-ETS). Ireland is an interesting case study due to the role of agriculture (a particularly challenging sector with regard to GHG emissions reduction), that represents 29% of Ireland's GHG emissions compared with less than 10% for the EU. The analysis is carried out with the Irish TIMES model, a bottom-up energy systems modelling tool with detailed characterization of Ireland's energy system. The paper uses scenario analysis to provide pathways that demonstrate how Ireland can meet the non-ETS target at least cost. The paper considers the impacts (in terms of different technology choices and higher marginal abatement costs) arising from higher targets for the energy system to compensate for growth in agriculture activity and low mitigation potential in that sector. The results point to a need to reconsider Ireland's renewable energy focus, with a need for increased effort in renewable transport and renewable heat in particular. The results also point to significant electrification of residential heating. The results also point to a high marginal abatement cost (€213/tCO2), which challenges the analysis carried out at EU level to establish Ireland's non-ETS target. - Highlights: • Techno-economic energy model to deliver EU GHG mitigation target by 2020 in Ireland. • Agriculture represents nearly half of Non-ETS emissions in Ireland. • The target set for Non-ETS GHG for Ireland is far from a cost optimal target. • The results point to a need to reconsider Ireland's renewable energy focus. • Key pathways: electrification of heating in buildings and biofuels in transport

  10. Will targeting oropharyngeal gonorrhoea delay the further emergence of drug-resistant Neisseria gonorrhoeae strains?

    Science.gov (United States)

    Lewis, D A

    2015-06-01

    Gonorrhoea is an important sexually transmitted infection associated with serious complications and enhanced HIV transmission. Oropharyngeal infections are often asymptomatic and will only be detected by screening. Gonococcal culture has low sensitivity (gonorrhoea, and, although not yet approved commercially, nucleic acid amplification tests (NAAT) are the assay of choice. Screening for oropharyngeal gonorrhoea should be performed in high-risk populations, such as men-who-have-sex-with-men(MSM). NAATs have a poor positive predictive value when used in low-prevalence populations. Gonococci have repeatedly thwarted gonorrhoea control efforts since the first antimicrobial agents were introduced. The oropharyngeal niche provides an enabling environment for horizontal transfer of genetic material from commensal Neisseria and other bacterial species to Neisseria gonorrhoeae. This has been the mechanism responsible for the generation of mosaic penA genes, which are responsible for most of the observed cases of resistance to extended-spectrum cephalosporins (ESC). As antimicrobial-resistant gonorrhoea is now an urgent public health threat, requiring improved antibiotic stewardship, laboratory-guided recycling of older antibiotics may help reduce ESC use. Future trials of antimicrobial agents for gonorrhoea should be powered to test their efficacy at the oropharynx as this is the anatomical site where treatment failure is most likely to occur. It remains to be determined whether a combination of frequent screening of high-risk individuals and/or laboratory-directed fluoroquinolone therapy of oropharyngeal gonorrhoea will delay the further emergence of drug-resistant N. gonorrhoeae strains. PMID:25911525

  11. Spontaneous autoimmune thyroiditis in obese strain chickens: a genetic analysis of target organ abnormalities

    International Nuclear Information System (INIS)

    In this study the authors investigated the genetic background of primary abnormalities found in the thyroid gland of Obese strain (OS) chickens with spontaneous autoimmune thyroiditis (SAT), i.e., susceptibility to passively transferred antibodies to thyroglobulin (TgAb) and incomplete suppression of iodine uptake by thyroxine (T4). Several crosses between the B15/B15 subline of OS chickens and the inbred CB line (B12/B12) were done and the progeny was analyzed for thyroiditis after injection of OS serum containing high titers of TgAb. It was found that passive transfer of TgAb increased the lymphoid infiltration in the thyroids of OS chickens, but had no effect on CB birds. A genetic analysis of backcrosses revealed that this trait is, in the case of simple Mendelian inheritance, encoded by at least three recessive genes. The thyroidal 131I uptake of these crosses under T4 was also determined and they found that this trait is most probably encoded by only one recessive gene

  12. Targeted molecular therapies against epidermal growth factor receptor: Past experiences and challenges

    OpenAIRE

    Reardon, David A.; Wen, Patrick Y.; Mellinghoff, Ingo K.

    2014-01-01

    Epidermal growth factor receptor (EGFR) has emerged as a highly attractive therapeutic target in glioblastoma (GBM) based on its high frequency of gene amplification and mutation and its identification as an upstream trigger of dysregulated cell signaling cascades that drive GBM pathophysiology. Extensive investment has been committed in an attempt to exploit EGFR therapeutically to improve outcome for GBM patients, including the development of a variety of EGFR-targeting therapeutics as well...

  13. The adopting inflation targeting in the monetary policy of emerging countries: challenges and issues

    OpenAIRE

    chrigui zouhair; younes boujelbene

    2010-01-01

    In this paper, our main objective is to verify the ability of inflation targeting to achieve better results concerning inflation, production and interest rate, with a new sample related to some emerging countries. Therefore, we have studied the opportunities stemming from the adoption of inflation targeting during a time period ranging from 1975 to 2005 dealing with a sample of Emerging Asians Countries as compared to Emerging North African ones. Our contribution consists in debating the dive...

  14. Targeted therapies in cancer - challenges and chances offered by newly developed techniques for protein analysis in clinical tissues

    Directory of Open Access Journals (Sweden)

    K Malinowsky, C Wolff, S Gündisch, D Berg, KF Becker

    2011-01-01

    Full Text Available In recent years, new anticancer therapies have accompanied the classical approaches of surgery and radio- and chemotherapy. These new forms of treatment aim to inhibit specific molecular targets namely altered or deregulated proteins, which offer the possibility of individualized therapies.The specificity and efficiency of these new approaches, however, bring about a number of challenges. First of all, it is essential to specifically identify and quantify protein targets in tumor tissues for the reasonable use of such targeted therapies. Additionally, it has become even more obvious in recent years that the presence of a target protein is not always sufficient to predict the outcome of targeted therapies. The deregulation of downstream signaling molecules might also play an important role in the success of such therapeutic approaches. For these reasons, the analysis of tumor-specific protein expression profiles prior to therapy has been suggested as the most effective way to predict possible therapeutic results. To further elucidate signaling networks underlying cancer development and to identify new targets, it is necessary to implement tools that allow the rapid, precise, inexpensive and simultaneous analysis of many network components while requiring only a small amount of clinical material.Reverse phase protein microarray (RPPA is a promising technology that meets these requirements while enabling the quantitative measurement of proteins. Together with recently developed protocols for the extraction of proteins from formalin-fixed, paraffin-embedded (FFPE tissues, RPPA may provide the means to quantify therapeutic targets and diagnostic markers in the near future and reliably screen for new protein targets.With the possibility to quantitatively analyze DNA, RNA and protein from a single FFPE tissue sample, the methods are available for integrated patient profiling at all levels of gene expression, thus allowing optimal patient stratification

  15. Modelling the impacts of challenging 2050 European climate mitigation targets on Ireland’s energy system

    International Nuclear Information System (INIS)

    The Copenhagen Accord established political consensus on the 2 °C limit (in global temperature increase) and for deep cuts in greenhouse gas (GHG) emissions levels to achieve this goal. The European Union has set ambitious GHG targets for the year 2050 (80–95% below 1990 levels), with each Member State developing strategies to contribute to these targets. This paper focuses on mitigation targets for one Member State, Ireland, an interesting case study due to the growth in GHG emissions (24% increase between 1990 and 2005) and the high share of emissions from agriculture (30% of total GHG emissions). We use the Irish TIMES energy systems modelling tool to build a number of scenarios delivering an 80% emissions reduction target by 2050, including accounting for the limited options for agriculture GHG abatement by increasing the emissions reduction target for the energy system. We then compare the scenario results in terms of changes in energy technology, the role of energy efficiency and renewable energy. We also quantify the economic impacts of the mitigation scenarios in terms of marginal CO2 abatement costs and energy system costs. The paper also sheds light on the impacts of short term targets and policies on long term mitigation pathways. - Highlights: ► We developed a techno-economic energy model of Ireland to the year 2050. ► Reductions between 80% and 95% of GHG emissions can be technically achieved. ► A 50% emissions cut in agriculture requires a 95% reductions from the energy system. ► Extending current policies implies greater electrification and efficiency measures. ► The additional cost to achieve mitigation remain less than 2% of GDP levels in 2050.

  16. Evaluation of the protection elicited by direct and indirect exposure to live attenuated infectious laryngotracheitis virus vaccines against a recent challenge strain from the United States.

    Science.gov (United States)

    Rodríguez-Avila, Andrés; Oldoni, Ivomar; Riblet, Sylva; Garcia, Maricarmen

    2008-06-01

    In a recent study (Oldoni & García, 2007), some field strains of infectious laryngotracheitis viruses (ILTV) were characterized as genotypically different (group VI) from ILT vaccine strains. The objective of this study was to evaluate the protection elicited by one chicken embryo origin (CEO) and one tissue culture origin (TCO) vaccine against a field isolate from group VI after direct and indirect exposure to ILTV live attenuated vaccines. In phase 1 of the experiment, non-vaccinated chickens were placed into contact with the eye drop vaccinates for a period of four weeks after vaccination. Transmission of the vaccine virus to these in-contact birds was demonstrated by real time PCR and antibody production, although the in-contact birds did not become protected against disease when subsequently challenged in phase 2 of the experiment. This emphasized the importance of uniform vaccination to obtain adequate protection, both to avoid the occurrence of susceptible chickens, and to minimize the potential for reversion to virulence of live-attenuated vaccines. In phase 2, protection against challenge with a group VI field virus was assessed four weeks after vaccination by scoring clinical signs and mortality, and quantifying weight gain. Sentinel birds were added to the groups one day after challenge to assess shedding of challenge virus, using real time PCR and virus isolation, during the period 2 to 12 days post challenge. The results showed that the CEO and TCO eye drop-vaccinated chickens were protected against challenge with the group VI virus, even though it was genetically different from the vaccine strains, and that challenge virus was not transmitted from these protected birds to the sentinels. PMID:18568655

  17. Recent Advancements in Targeted Delivery of Therapeutic Molecules in Neurodegenerative Disease - Spinocerebellar Ataxia - Opportunities and Challenges

    Directory of Open Access Journals (Sweden)

    Satya Prakash

    2008-01-01

    Full Text Available Drug discovery and its methodologies have been very effective in terms of treating cancers and immunological disorders but have not been able to stop genetic diseases as most of the drugs target at the protein level. They merely mitigate the symptoms of the disease. Spinocerebellar ataxia is a neurological genetic disorder that is caused by the formation of an abnormal protein. There have been several reports on ataxic drug development but actual clinical treatment is yet to be achieved. Oligonucleotide therapy called sequence specific siRNA mediated gene silencing has evolved with promising results. This approach emphasizes on suppressing the expression of the diseased gene at mRNA level. However, there is a limitation in delivery of siRNA to the target site. Several methods have been developed over the last decade to enhance the target specific delivery of DNA, siRNA, protein and small drug molecules for therapeutic purpose with less or no side effects. This review discusses the latest upcoming technologies in the field that focus on a number of nonviral nanocarriers for targeted delivery. In this review, we explore the promise and potential of novel therapeutics with interest on ataxia therapy.

  18. Molecular Characterization of Legionellosis Drug Target Candidate Enzyme Phosphoglucosamine Mutase from Legionella pneumophila (strain Paris): An In Silico Approach

    Science.gov (United States)

    Mazumder, Habibul Hasan; Khan, Arif; Hossain, Mohammad Uzzal; Chowdhury, Homaun Kabir

    2014-01-01

    The harshness of legionellosis differs from mild Pontiac fever to potentially fatal Legionnaire's disease. The increasing development of drug resistance against legionellosis has led to explore new novel drug targets. It has been found that phosphoglucosamine mutase, phosphomannomutase, and phosphoglyceromutase enzymes can be used as the most probable therapeutic drug targets through extensive data mining. Phosphoglucosamine mutase is involved in amino sugar and nucleotide sugar metabolism. The purpose of this study was to predict the potential target of that specific drug. For this, the 3D structure of phosphoglucosamine mutase of Legionella pneumophila (strain Paris) was determined by means of homology modeling through Phyre2 and refined by ModRefiner. Then, the designed model was evaluated with a structure validation program, for instance, PROCHECK, ERRAT, Verify3D, and QMEAN, for further structural analysis. Secondary structural features were determined through self-optimized prediction method with alignment (SOPMA) and interacting networks by STRING. Consequently, we performed molecular docking studies. The analytical result of PROCHECK showed that 95.0% of the residues are in the most favored region, 4.50% are in the additional allowed region and 0.50% are in the generously allowed region of the Ramachandran plot. Verify3D graph value indicates a score of 0.71 and 89.791, 1.11 for ERRAT and QMEAN respectively. Arg419, Thr414, Ser412, and Thr9 were found to dock the substrate for the most favorable binding of S-mercaptocysteine. However, these findings from this current study will pave the way for further extensive investigation of this enzyme in wet lab experiments and in that way assist drug design against legionellosis. PMID:25705169

  19. High purity materials as targets for radioisotope production: Needs and challenges

    Indian Academy of Sciences (India)

    V Shivarudrappa; K V Vimalnath

    2005-07-01

    Radionuclides have become powerful and indispensable tools in many endeavours of human activities, most importantly in medicine, industry, biology and agriculture, apart from R&D activities. Ready availability of radionuclides in suitable radiochemical form, its facile detection and elegant tracer concepts are responsible for their unprecedented use. Application of radioisotopes in medicine has given birth to a new branch, viz. nuclear medicine, wherein radioisotopes are used extensively in the diagnosis and treatment of variety of diseases including cancer. Artificial transmutation of an element employing thermal neutrons in a reactor or high energy particle accelerators (cyclotrons) are the routes of radioisotope production world over. Availability of high purity target materials, natural or enriched, are crucial for any successful radioisotope programme. Selection of stable nuclides in suitable chemical form as targets with desired isotopic and chemical purity are among the important considerations in radioisotope production. Mostly the oxide, carbonate or the metal itself are the preferred target forms for neutron activation in a research reactor. Chemical impurities, particularly from the elements of the same group, put a limitation on the purity of the final radioisotope product. Whereas the isotopic impurities result in the production of undesirable radionuclidic impurities, which affect their effective utilization. Isotope Group, BARC, is in the forefront of radioisotope production and supply in the country, meeting demands for gamut of radioisotope applications indigenously for over four decades now. Radioisotopes such as 131I, 99Mo, 32P, 51Cr, 153Sm, 82Br, 203Hg, 198Au etc are produced in TBq quantities every month and supplied to several users and to Board of Radiation and Isotope Technology (BRIT). Such a large production programme puts a huge demand on the reliable sources of availability of high purity target materials which are at present mostly met

  20. Hitting the right target: taxonomic challenges for, and of, plant invasions

    OpenAIRE

    Pyšek, Petr; Hulme, Philip E.; Meyerson, Laura A.; Smith, Gideon F; James S Boatwright; Crouch, Neil R; Figueiredo, Estrela; Llewellyn C. Foxcroft; Jarošík, Vojtěch; Richardson, David M.; Suda, Jan; Wilson, John R. U.

    2013-01-01

    This paper explores how a lack of taxonomic expertise, and by implication a dearth of taxonomic products such as identification tools, has hindered progress in understanding and managing biological invasions. It also explores how the taxonomic endeavour could benefit from studies of invasive species. We review the literature on the current situation in taxonomy with a focus on the challenges of identifying alien plant species and explore how this has affected the study of biological invasions...

  1. Local host response following an intramammary challenge with Staphylococcus fleurettii and different strains of Staphylococcus chromogenes in dairy heifers.

    Science.gov (United States)

    Piccart, Kristine; Verbeke, Joren; De Visscher, Anneleen; Piepers, Sofie; Haesebrouck, Freddy; De Vliegher, Sarne

    2016-01-01

    Coagulase-negative staphylococci (CNS) are a common cause of subclinical mastitis in dairy cattle. The CNS inhabit various ecological habitats, ranging between the environment and the host. In order to obtain a better insight into the host response, an experimental infection was carried out in eight healthy heifers in mid-lactation with three different CNS strains: a Staphylococcus fleurettii strain originating from sawdust bedding, an intramammary Staphylococcus chromogenes strain originating from a persistent intramammary infection (S. chromogenes IM) and a S. chromogenes strain isolated from a heifer's teat apex (S. chromogenes TA). Each heifer was inoculated in the mammary gland with 1.0 × 10(6) colony forming units of each bacterial strain (one strain per udder quarter), whereas the remaining quarter was infused with phosphate-buffered saline. Overall, the CNS evoked a mild local host response. The somatic cell count increased in all S. fleurettii-inoculated quarters, although the strain was eliminated within 12 h. The two S. chromogenes strains were shed in larger numbers for a longer period. Bacterial and somatic cell counts, as well as neutrophil responses, were higher after inoculation with S. chromogenes IM than with S. chromogenes TA. In conclusion, these results suggest that S. chromogenes might be better adapted to the mammary gland than S. fleurettii. Furthermore, not all S. chromogenes strains induce the same local host response. PMID:27176792

  2. Differentiation of Mycoplasma gallisepticum vaccine strains ts-11 and 6/85 from commonly used Mycoplasma gallisepticum challenge strains by PCR

    Science.gov (United States)

    Mycoplasma gallisepticum (MG) is an important avian pathogen causing significant economic losses within the poultry layer industry. In an effort to develop tools to aid in MG research and diagnostics, we have compared available sequences of the attenuated MG vaccine strain ts-11 to those of commonl...

  3. Non-target trials with Pseudomonas fluorescens strain CL145A, a lethal control agent of dreissenid mussels (Bivalvia: Dreissenidae

    Directory of Open Access Journals (Sweden)

    Daniel P. Molloy

    2013-01-01

    Full Text Available In an effort to develop an efficacious and environmentally safe method for managing zebra mussels (Dreissena polymorpha and quaggamussels (Dreissena rostriformis bugensis, we initiated a research project investigating the potential use of bacteria and their naturalmetabolic products as biocontrol agents. This project resulted in the discovery of an environmental isolate lethal to dreissenid mussels,Pseudomonas fluorescens strain CL145A (Pf-CL145A. In previous published reports we have demonstrated that: 1 Pf-CL145A’s mode ofaction is intoxication (not infection; 2 natural product within ingested bacterial cells lyse digestive tract epithelial cells leading to dreisseniddeath; and 3 high dreissenid kill rates (>90% are achievable following treatment with Pf-CL145A cells, irrespective of whether thebacterial cells are dead or alive. Investigating the environmental safety of Pf-CL145A was also a key element in our research efforts, andherein, we report the results of non-target trials demonstrating Pf-CL145A’s high specificity to dreissenids. These acute toxicity trials weretypically single-dose, short-term (24-72 h exposures to Pf-CL145A cells under aerated conditions at concentrations highly lethal todreissenids (100 or 200 mg/L. These trials produced no evidence of mortality among the ciliate Colpidium colpoda, the cladoceran Daphniamagna, three fish species (Pimephales promelas, Salmo trutta, and Lepomis macrochirus, and seven bivalve species (Mytilus edulis,Pyganodon grandis, Pyganodon cataracta, Lasmigona compressa, Strophitus undulatus, Lampsilis radiata, and Elliptio complanata. Lowmortality (3-27% was recorded in the amphipod Hyalella azteca, but additional trials suggested that most, if not all, of the mortality couldbe attributed to some other unidentified factor (e.g., possibly particle load or a water quality issue rather than Pf-CL145A’s dreissenidkillingnatural product. In terms of potential environmental safety, the results of

  4. Targeting cancer cells in the tumor microenvironment: opportunities and challenges in combinatorial nanomedicine.

    Science.gov (United States)

    Linton, Samuel S; Sherwood, Samantha G; Drews, Kelly C; Kester, Mark

    2016-01-01

    Cancer therapies of the future will rely on synergy between drugs delivered in combination to achieve both maximum efficacy and decreased toxicity. Nanoscale drug delivery vehicles composed of highly tunable nanomaterials ('nanocarriers') represent the most promising approach to achieve simultaneous, cell-selective delivery of synergistic ratios of combinations of drugs within solid tumors. Nanocarriers are currently being used to co-encapsulate and deliver synergistic ratios of multiple anticancer drugs to target cells within solid tumors. Investigators exploit the unique environment associated with solid tumors, termed the tumor microenvironment (TME), to make 'smart' nanocarriers. These sophisticated nanocarriers exploit the pathological conditions in the TME, thereby creating highly targeted nanocarriers that release their drug payload in a spatially and temporally controlled manner. The translational and commercial potential of nanocarrier-based combinatorial nanomedicines in cancer therapy is now a reality as several companies have initiated human clinical trials. PMID:26153136

  5. Bioinformatic Challenges in Clinical Diagnostic Application of Targeted Next Generation Sequencing: Experience from Pheochromocytoma.

    Directory of Open Access Journals (Sweden)

    Joakim Crona

    Full Text Available Recent studies have demonstrated equal quality of targeted next generation sequencing (NGS compared to Sanger Sequencing. Whereas these novel sequencing processes have a validated robust performance, choice of enrichment method and different available bioinformatic software as reliable analysis tool needs to be further investigated in a diagnostic setting.DNA from 21 patients with genetic variants in SDHB, VHL, EPAS1, RET, (n=17 or clinical criteria of NF1 syndrome (n=4 were included. Targeted NGS was performed using Truseq custom amplicon enrichment sequenced on an Illumina MiSEQ instrument. Results were analysed in parallel using three different bioinformatics pipelines; (1 Commercially available MiSEQ Reporter, fully automatized and integrated software, (2 CLC Genomics Workbench, graphical interface based software, also commercially available, and ICP (3 an in-house scripted custom bioinformatic tool.A tenfold read coverage was achieved in between 95-98% of targeted bases. All workflows had alignment of reads to SDHA and NF1 pseudogenes. Compared to Sanger sequencing, variant calling revealed a sensitivity ranging from 83 to 100% and a specificity of 99.9-100%. Only MiSEQ reporter identified all pathogenic variants in both sequencing runs.We conclude that targeted next generation sequencing have equal quality compared to Sanger sequencing. Enrichment specificity and the bioinformatic performance need to be carefully assessed in a diagnostic setting. As acceptable accuracy was noted for a fully automated bioinformatic workflow, we suggest that processing of NGS data could be performed without expert bioinformatics skills utilizing already existing commercially available bioinformatics tools.

  6. Current Challenges in Prostate Cancer Management and the Rationale behind Targeted Focal Therapy

    Directory of Open Access Journals (Sweden)

    Al B. Barqawi

    2012-01-01

    Full Text Available Among men, prostate cancer has a high prevalence, with relatively lower cancer-specific mortality risk compared to lung and colon cancer. Prostate-specific antigen (PSA screening has increased prostate cancer awareness since its implementation as a screening tool almost 25 years ago, but, due to the largely indolent course of this disease and the unspecific nature of the PSA test, increased incidence has largely been associated with cancers that would not go on to cause death (clinically insignificant, leading to an overdiagnosis challenge and an ensuing overtreatment consequences. The overtreatment problem is exacerbated by the high risk of side effects that current treatment techniques have, putting patients’ quality of life at risk with little or no survival benefit. The goals of this paper are to evaluate the rise, prevalence, and impact of the overdiagnosis and ensuing overtreatment problems, as well as highlight potential solutions. In this effort, a review of major epidemiological and screening studies, cancer statistics from the advent of prostate-specific antigen screening to the present, and reports on patient concerns and treatment outcomes was conducted to present the dominant factors that underlie current challenges in prostate cancer treatment and illuminate potential solutions.

  7. The sustainability challenge of meeting carbon dioxide targets in Europe by 2020

    International Nuclear Information System (INIS)

    Following the Kyoto Protocol, the European Union obligated itself to lower its greenhouse gas (GHG) emissions 20% below their 1990 level, by the year 2020. Carbon dioxide is the major GHG. To fulfil this obligation, the nations must meet the sustainability challenge of countering rising population plus affluence with the dematerialization of less energy per GDP plus the decarbonization of less carbon per energy. To test the feasibility of meeting the challenge, we analysed carbon dioxide emission during 1993-2004. Although emissions in the entire Union grew only by an average of 0.31% per year, emissions and their drivers varied markedly among the 27 member states. Dematerialization and decarbonization did occur, but not enough to offset the slight population growth plus rapidly increasing affluence. To fulfil its obligation in the next 12 years, the EU27 would have to counter its increasing population and affluence by a combined dematerialization and decarbonization 1.9-2.6 times faster than during 1993-2004. Hence, fulfilling its obligation by addressing fossil carbon emissions alone is very unlikely

  8. The sustainability challenge of meeting carbon dioxide targets in Europe by 2020

    International Nuclear Information System (INIS)

    Following the Kyoto Protocol, the European Union obligated itself to lower its greenhouse gas (GHG) emissions 20% below their 1990 level, by the year 2020. Carbon dioxide is the major GHG. To fulfil this obligation, the nations must meet the sustainability challenge of countering rising population plus affluence with the dematerialization of less energy per GDP plus the decarbonization of less carbon per energy. To test the feasibility of meeting the challenge, we analysed carbon dioxide emission during 1993-2004. Although emissions in the entire Union grew only by an average of 0.31% per year, emissions and their drivers varied markedly among the 27 member states. Dematerialization and decarbonization did occur, but not enough to offset the slight population growth plus rapidly increasing affluence. To fulfil its obligation in the next 12 years, the EU27 would have to counter its increasing population and affluence by a combined dematerialization and decarbonization 1.9-2.6 times faster than during 1993-2004. Hence, fulfilling its obligation by addressing fossil carbon emissions alone is very unlikely. (author)

  9. PARASITE STRAIN SPECIFICITY OF PRECURSOR CYTOTOXIC T-CELLS IN INDIVIDUAL ANIMALS CORRELATES WITH CROSS-PROTECTION IN CATTLE CHALLENGED WITH THEILERIA-PARVA

    OpenAIRE

    Taracha, ELN; Goddeeris, Bruno; MORZARIA, SP; Morrison, WI

    1995-01-01

    Class I major histocompatibility complex-restricted parasite-specific cytotoxic T lymphocytes (CTL) are known to be a major component of the bovine immune response to the protozoan parasite Theileria parva, but formal proof for their role in protection of cattle against infection with T. parva has been lacking. Animals immunized with one stock of T. parva show variations in the degree of protection against heterologous challenge and also in the parasite strain specificity of their CTL respons...

  10. Employee Anonymous Online Dissent: Dynamics and Ethical Challenges for Employees, Targeted Organisations, Online Outlets and Audiences

    DEFF Research Database (Denmark)

    Ravazzani, Silvia; Mazzei, Alessandra

    2015-01-01

    remaining accountable for them and avoiding emotion-focused and defensive disclosure. Targeted organisations need to prevent external disclosure while ensuring freedom of speech and employee privacy, and to respond effectively when overt criticism is found online. Other tensions concern online outlet......This paper aims to enhance understanding of dissent expressive acts that employees voice via anonymous online public contexts. Based on literature on organisational dissent, anonymity and online disclosure, we first point out key dynamics of employee anonymous online dissent, and then present...

  11. Host factors determine anti-GM1 response following oral challenge of chickens with Guillain-Barre syndrome derived Campylobacter jejuni strain GB11.

    Directory of Open Access Journals (Sweden)

    C Wim Ang

    Full Text Available BACKGROUND: Anti-ganglioside antibodies with a pathogenic potential are present in C. jejuni-associated Guillain-Barré syndrome (GBS patients and are probably induced by molecular mimicry. Immunization studies in rabbits and mice have demonstrated that these anti-ganglioside antibodies can be induced using purified lipo-oligosaccharides (LOS from C. jejuni in a strong adjuvant. METHODOLOGY/PRINCIPAL FINDINGS: To investigate whether natural colonization of chickens with a ganglioside-mimicking C. jejuni strain induces an anti-ganglioside response, and to investigate the diversity in anti-ganglioside response between and within genetically different chicken lines, we orally challenged chickens with different C. jejuni strains. Oral challenge of chickens with a C. jejuni strain from a GBS patient, containing a LOS that mimics ganglioside GM1, induced specific IgM and IgG anti-LOS and anti-GM1 antibodies. Inoculation of chickens with the Penner HS:3 serostrain, without a GM1-like structure, induced anti-LOS but no anti-ganglioside antibodies. We observed different patterns of anti-LOS/ganglioside response between and within the five strains of chickens. CONCLUSIONS: Natural infection of chickens with C. jejuni induces anti-ganglioside antibodies. The production of antibodies is governed by both microbial and host factors.

  12. Brucella suis S2, brucella melitensis Rev. 1 and Brucella abortus S19 living vaccines: residual virulence and immunity induced against three Brucella species challenge strains in mice.

    Science.gov (United States)

    Bosseray, N; Plommet, M

    1990-10-01

    Live attenuated Brucella suis S2 vaccine was compared to living vaccines B. abortus S19 and B. melitensis Rev. 1 in mice. Residual virulence was estimated by ability to multiply and persist in spleen and lymph nodes. Immunogenicity was estimated by spleen counts of control and vaccinated mice challenged either with the reference B. abortus 544 strain or with virulent B. melitensis H38 and B. suis 1330 strains. S2 vaccine had lower residual virulence; expressed as 50% recovery time, persistence was 4.3 weeks, compared to 7.1 and 9.0 weeks for S19 and Rev. 1 vaccines. Immunity induced by the three vaccines was similar 45 days after vaccination. At 150 days, immunity by S19 and Rev.1 was still similar against the three challenge strains. In contrast, immunity induced by S2 had declined against the B. melitensis strain. Thus, a recall vaccination may be required for vaccination of sheep to confer a long-lasting immunity. PMID:2123586

  13. Host-targeting agents for prevention and treatment of chronic hepatitis C - perspectives and challenges.

    Science.gov (United States)

    Zeisel, Mirjam B; Lupberger, Joachim; Fofana, Isabel; Baumert, Thomas F

    2013-02-01

    Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and hepatocellular carcinoma worldwide. Furthermore, HCV-induced liver disease is a major indication of liver transplantation. In the past years, direct-acting antivirals (DAAs) targeting HCV enzymes have been developed. DAAs increase the virologic response to anti-HCV therapy but may lead to selection of drug-resistant variants and treatment failure. To date, strategies to prevent HCV infection are still lacking and antiviral therapy in immunocompromised patients, patients with advanced liver disease and HIV/HCV-co-infection remains limited. Alternative or complementary approaches addressing the limitations of current antiviral therapies are to boost the host's innate immunity or interfere with host factors required for pathogenesis. Host-targeting agents (HTAs) provide an interesting perspective for novel antiviral strategies against viral hepatitis since they have (i) a high genetic barrier to resistance, (ii) a pan-genotypic antiviral activity, and (iii) complementary mechanisms of action to DAAs and might therefore act in a synergistic manner with current standard of care or DAAs in clinical development. This review highlights HTAs against HCV infection that have potential as novel antivirals and are in preclinical or clinical development. PMID:23041307

  14. The challenge of targeting EGFR: experience with gefitinib in nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    C.L. Watkins

    2010-09-01

    Full Text Available As the first approved epidermal growth factor receptor (EGFR-targeted therapy for nonsmall cell lung cancer (NSCLC, the clinical development of gefitinib was complex. Advances in scientific understanding of the target biology during its clinical development enabled the identification of a biomarker to define patients most likely to derive benefit from gefitinib. Initial phase II trials showed clinically meaningful anti-tumour activity in 12–18% of unselected pretreated patients with advanced NSCLC at the optimum biological dose (250 mg. Subgroup analyses of these and subsequent phase III trials in unselected patients suggested that EGFR mutation and some clinical characteristics associated with a higher incidence of EGFR mutation (Asian ethnicity, adenocarcinoma histology, never-smoking and female sex were linked with increased response to gefitinib. Consequently, the IRESSA Pan-Asia Study (IPASS was conducted in never-smokers or former light-smokers in East Asia who had adenocarcinoma of the lung. IPASS showed that EGFR mutation was the strongest predictor of improved progression-free survival (mutation-positive subgroup hazard ratio (HR 0.48, 95% CI 0.36–0.64 (p<0.001, n = 261; mutation-negative subgroup HR 2.85, 95% CI 2.05–3.98 (p<0.001, n = 176; interaction test p<0.001 with gefitinib versus carboplatin/paclitaxel as first-line therapy for advanced NSCLC. Important lessons for the development of future personalised medicines are discussed.

  15. Challenges and Opportunities in the Discovery of New Therapeutics Targeting the Kynurenine Pathway.

    Science.gov (United States)

    Dounay, Amy B; Tuttle, Jamison B; Verhoest, Patrick R

    2015-11-25

    The kynurenine pathway is responsible for the metabolism of more than 95% of dietary tryptophan (TRP) and produces numerous bioactive metabolites. Recent studies have focused on three enzymes in this pathway: indoleamine dioxygenase (IDO1), kynurenine monooxygenase (KMO), and kynurenine aminotransferase II (KAT II). IDO1 inhibitors are currently in clinical trials for the treatment of cancer, and these agents may also have therapeutic utility in neurological disorders, including multiple sclerosis. KMO inhibitors are being investigated as potential treatments for neurodegenerative diseases, such as Huntington's and Alzheimer's diseases. KAT II inhibitors have been proposed in new therapeutic approaches toward psychiatric and cognitive disorders, including cognitive impairment associated with schizophrenia. Numerous medicinal chemistry studies are currently aimed at the design of novel, potent, and selective inhibitors for each of these enzymes. The emerging opportunities and significant challenges associated with pharmacological modulation of these enzymes will be explored in this review. PMID:26207924

  16. Identification and characterization of miR-92a and its targets modulating Vibrio splendidus challenged Apostichopus japonicus.

    Science.gov (United States)

    Zhang, Pengjuan; Li, Chenghua; Shao, Yina; Chen, Xiaochong; Li, Ye; Su, Xiurong; Li, Taiwu

    2014-06-01

    miR-92a is a kind of disease related fine-tuning regulator which is not only related with tumorigenesis and tumor development but also participates in host-pathogen interaction in vertebrates. In present study, the potential targets of miR-92a in Apostichopus japonicus coelomocytes were screened by high-throughout sequencing and PCR approaches. Total of 10 annotated candidates were identified by hybrid PCR, and 23 were verified from RNA-seq, in which SMURF, PCBP and MEGF were found in both methods. The expression patterns of miR-92a and some putative targets were further characterized by qPCR at cell and individual levels. Vibrio splendidus and LPS exposure could significantly increase the expression level of sea cucumber miR-92a at all examined time points. Accordingly, strictly negative correlation expression profiles were detected in two candidates genes of MEGF and SMURF, suggesting that these two genes showed higher possibilities to be the targets of miR-92a in sea cucumber. Overall, the present work will enhance our understanding in the context of miR-92a modulating the interaction of sea cucumber upon pathogen challenged. PMID:24747055

  17. Targeting the Psychosexual Challenges Faced by Couples with Breast Cancer: Can Couples Group Psychotherapy Help?

    Science.gov (United States)

    Lagana, Luciana; Fobair, Patricia; Spiegel, David

    2016-01-01

    The need for the psychosexual rehabilitation of breast cancer survivors and their intimate partners is underscored by the high prevalence of multiple psychosexual difficulties encountered by this patient population. Concerns about health, sexuality, and emotional distress are common among women with breast cancer and are often related to the side effects of cancer treatment. Additionally, both intimate relationship problems and partners’ distress are likely to influence patients’ psychosexual health. A clearer understanding of these complex clinical issues is needed in order to implement effective psychosexual rehabilitation interventions. In this article, we extended the use of the manualized and empirically validated Supportive-Expressive Group Therapy (SEGT) model to target the specific psychosexual needs of couples with breast (as well as other types of) cancer. In view of the pertinent literature in this area and based on our clinical experience utilizing this group therapy model with different patient populations, we have discussed how clinicians involved in the psychosexual care of oncology patients could apply such a model within a couples group therapy format. PMID:27239398

  18. Therapeutic hypothermia and targeted temperature management in traumatic brain injury: Clinical challenges for successful translation.

    Science.gov (United States)

    Dietrich, W Dalton; Bramlett, Helen M

    2016-06-01

    The use of therapeutic hypothermia (TH) and targeted temperature management (TTM) for severe traumatic brain injury (TBI) has been tested in a variety of preclinical and clinical situations. Early preclinical studies showed that mild reductions in brain temperature after moderate to severe TBI improved histopathological outcomes and reduced neurological deficits. Investigative studies have also reported that reductions in post-traumatic temperature attenuated multiple secondary injury mechanisms including excitotoxicity, free radical generation, apoptotic cell death, and inflammation. In addition, while elevations in post-traumatic temperature heightened secondary injury mechanisms, the successful implementation of TTM strategies in injured patients to reduce fever burden appear to be beneficial. While TH has been successfully tested in a number of single institutional clinical TBI studies, larger randomized multicenter trials have failed to demonstrate the benefits of therapeutic hypothermia. The use of TH and TTM for treating TBI continues to evolve and a number of factors including patient selection and the timing of the TH appear to be critical in successful trial design. Based on available data, it is apparent that TH and TTM strategies for treating severely injured patients is an important therapeutic consideration that requires more basic and clinical research. Current research involves the evaluation of alternative cooling strategies including pharmacologically-induced hypothermia and the combination of TH or TTM approaches with more selective neuroprotective or reparative treatments. This manuscript summarizes the preclinical and clinical literature emphasizing the importance of brain temperature in modifying secondary injury mechanisms and in improving traumatic outcomes in severely injured patients. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26746342

  19. Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

    Directory of Open Access Journals (Sweden)

    Hohenforst-Schmidt W

    2013-07-01

    through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR negative stage IIIa–IV International Union Against Cancer 7 (UICC-7, and with Eastern Cooperative Oncology Group (ECOG 2 scores were administered platinum-based doublet chemotherapy using combined intratumoral-regional and intravenous route of administration. Cisplatin analogues were injected at 0.5%–1% concentration within the tumor lesion and proven malignant lymph nodes according to pretreatment histological/cytological results and the concentration of systemic infusion was decreased to 70% of a standard protocol. This combined intravenous plus intratumoral-regional chemotherapy is used as a first line therapy on this short series of patients. To the best of our knowledge this is the first report of direct treatment of involved lymph nodes with cisplatin by endobronchial ultrasound drug delivery with a needle without any adverse effects. The initial overall survival and local response are suggestive of a better efficacy compared to established doublet cisplatin–based systemic chemotherapy in (higher standard concentrations alone according to the UICC 7 database expected survival. An extensive search of the literature was performed to gather information of previously published literature of intratumoral chemo-drug administration and formulation for this treatment modality. Our study shows a favorable local response, more than a 50% reduction, for a massive tumor mass after administration of five sessions of intratumoral chemotherapy plus two cycles of low-dose intravenous chemotherapy according to our protocol. These encouraging results (even in very sick ECOG 2 patients with central obstructive non-small cell lung cancer having a worse prognosis and quality of

  20. Resistance of previously infected chimpanzees to successive challenges with a heterologous intraclade B strain of human immunodeficiency virus type 1.

    OpenAIRE

    Shibata, R; Siemon, C.; Cho, M W; Arthur, L. O.; Nigida, S M; Matthews, T; Sawyer, L A; Schultz, A.; Murthy, K K; Israel, Z; Javadian, A; Frost, P.; Kennedy, R C; Lane, H C; Martin, M. A.

    1996-01-01

    To test whether the protective effects of attenuated simian immunodeficiency virus vaccines in macaques were applicable to the human immunodeficiency virus type 1 (HIV-1)-chimpanzee system, two groups of animals, previously infected with HIV-1(IIIB) or HIV-1(SF2) were each challenged with a heterologous clade B virus, HIV-1(DH12). Following challenge, the parameters measured included virus isolation (from plasma, peripheral blood mononuclear cells, and lymph node tissue); quantitative DNA PCR...

  1. Strain dependent gene expression and neurochemical levels in the brain of zebrafish: Focus on a few alcohol related targets

    OpenAIRE

    Pan, Y.; Chaterjee, D; Gerlai, R.

    2012-01-01

    The zebrafish is becoming increasingly popular in behavior genetics because it may allow one to conduct large scale mutation and drug screens facilitating the discovery of mechanisms of complex traits. Strain differences in adult zebrafish behavior have already been reported, which may have important implications in neurobehavioral genetics. For example, we have found the AB and SF strains to differ in their behavioral responses to both acute and chronic alcohol exposure. In the current study...

  2. Comparative phenomics and targeted use of genomics reveals variation in carbon and nitrogen assimilation among different Brettanomyces bruxellensis strains.

    Science.gov (United States)

    Crauwels, S; Van Assche, A; de Jonge, R; Borneman, A R; Verreth, C; Troels, P; De Samblanx, G; Marchal, K; Van de Peer, Y; Willems, K A; Verstrepen, K J; Curtin, C D; Lievens, B

    2015-11-01

    Recent studies have suggested a correlation between genotype groups of Brettanomyces bruxellensis and their source of isolation. To further explore this relationship, the objective of this study was to assess metabolic differences in carbon and nitrogen assimilation between different B. bruxellensis strains from three beverages, including beer, wine, and soft drink, using Biolog Phenotype Microarrays. While some similarities of physiology were noted, many traits were variable among strains. Interestingly, some phenotypes were found that could be linked to strain origin, especially for the assimilation of particular α- and β-glycosides as well as α- and β-substituted monosaccharides. Based upon gene presence or absence, an α-glucosidase and β-glucosidase were found explaining the observed phenotypes. Further, using a PCR screen on a large number of isolates, we have been able to specifically link a genomic deletion to the beer strains, suggesting that this region may have a fitness cost for B. bruxellensis in certain fermentation systems such as brewing. More specifically, none of the beer strains were found to contain a β-glucosidase, which may have direct impacts on the ability for these strains to compete with other microbes or on flavor production. PMID:26135985

  3. Efficacy of a recombinant HVT-H5 vaccine against challenge with two genetically divergent Indonesian HPAI H5N1 strains.

    Science.gov (United States)

    Soejoedono, Retno D; Murtini, Sri; Palya, Vilmos; Felföldi, Balázs; Mató, Tamás; Gardin, Yannick

    2012-12-01

    The swift evolution rate of avian influenza (AI) H5N1 virus demands constant efforts to update inactivated vaccines to match antigenically with the emerging new field virus strains. Recently, a recombinant turkey herpesvirus (rHVT)-AI vaccine, rHVT-H5, expressing the HA gene of a highly pathogenic avian influenza (HPAI) H5N1 clade 2.2 A/Swan/Hungary/499/ 2006 strain inserted into FC-126 strain of HVT vector, has been developed to combat current threats in poultry industry. Here, we present the results of two trials where rHVT-H5 was tested alone or in combination with inactivated H5N1 vaccines (the latter vaccines contained antigens produced by using a clade 2.1.3 HPAI H5N1 virus [A/Ck/WestJava-Nagrak/2007] in the first trial or mixture of antigen produced by strain A/Ck/WestJava-Nagrak/2007 and A/Ck/Banten-Tangerang/2010 [bivalent vaccine] for second trial) in broiler chickens (Gallus gallus domesticus) carrying maternally derived antibodies to H5N1 and then challenged with Indonesian HPAI H5N1 field isolates. The effectiveness of vaccination was evaluated on the basis of clinical protection (morbidity and mortality) and measurement of virus shedding after challenge. Immune response to vaccination was followed by serology. In the first experiment, chickens were vaccinated at the day of hatch with rHVT-H5 alone (Group 1) or combined with inactivated vaccine at day old (Group 2) or at 10 days of age (Group 3). The chickens along with nonvaccinated hatch-mates were challenged at 28 days of age with the HPAI H5N1 field isolate dade 2.1.3 A/Chicken/WestJava-Subang/29/2007. Eighty, 100%, and 80% clinical protection was recorded in Group 1, 2, and 3, respectively. A similar experiment was performed a second time, but the chicks in Group 3 received the inactivated vaccine earlier, at 7 days of age. Challenge was performed at 28 days of age using a different H5N1 isolate, clade 2.1.3 A/Ck/Purwakarta-Cilingga/142/10. Clinical protection achieved in the second trial was 95

  4. Nuclear cooperation targets global challenges. States back main pillars of the IAEA's work to strengthen nuclear safety, verification and technology transfer

    International Nuclear Information System (INIS)

    States meeting at the 44th IAEA General Conference in Vienna have set a challenging agenda for international nuclear cooperation into the 21st century that targets issues of global safety, security, and sustainable development. They adopted resolutions endorsing the Agency's programmes for strengthening activities under its three main pillars of work - nuclear verification, safety, and technology - that are closely linked to major challenges before the world. The document presents the main actions taken during the conference

  5. Protective effects of intranasal immunization with recombinant glycoprotein d in pregnant BALB/c mice challenged with different strains of equine herpesvirus 1.

    Science.gov (United States)

    Fuentealba, N A; Zanuzzi, C N; Scrochi, M R; Sguazza, G H; Bravi, M E; Cid de la Paz, V; Corva, S G; Portiansky, E L; Gimeno, E J; Barbeito, C G; Galosi, C M

    2014-11-01

    Equine herpesvirus (EHV)-1 induces respiratory infection, neurological disorders and abortion in horses. Most of the currently available attenuated or inactivated vaccines against this infection are administered intramuscularly and only provide partial protection against the respiratory disease. The present study examines the effect of intranasal immunization with purified EHV-1 recombinant glycoprotein D (gD) in BALB/c mice followed by challenge with three different EHV-1 strains during early to mid-pregnancy. The induced viral infection was evaluated by virus isolation, DNA detection by polymerase chain reaction, histopathology and immunohistochemical localization of antigen in the lung, placenta and uterus. Non-immunized mice showed clinical signs of infection, positive virus isolation from lungs and uteri, and abortion induced by one of the virus strains. Endometrial lesions developed in some of these animals that have been described previously only in horses. Immunized mice and their offspring had no viral infection or typical lesions. Intranasally administered gD therefore induced partial or complete protection against three different EHV-1 strains in BALB/c mice. PMID:25124330

  6. Recombinant infectious bronchitis virus (IBV) H120 vaccine strain expressing the hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) protects chickens against IBV and NDV challenge.

    Science.gov (United States)

    Yang, Xin; Zhou, Yingshun; Li, Jianan; Fu, Li; Ji, Gaosheng; Zeng, Fanya; Zhou, Long; Gao, Wenqian; Wang, Hongning

    2016-05-01

    Infectious bronchitis (IB) and Newcastle disease (ND) are common viral diseases of chickens, which are caused by infectious bronchitis virus (IBV) and Newcastle disease virus (NDV), respectively. Vaccination with live attenuated strains of IBV-H120 and NDV-LaSota are important for the control of IB and ND. However, conventional live attenuated vaccines are expensive and result in the inability to differentiate between infected and vaccinated chickens. Therefore, there is an urgent need to develop new efficacious vaccines. In this study, using a previously established reverse genetics system, we generated a recombinant IBV virus based on the IBV H120 vaccine strain expressing the haemagglutinin-neuraminidase (HN) protein of NDV. The recombinant virus, R-H120-HN/5a, exhibited growth dynamics, pathogenicity and viral titers that were similar to those of the parental IBV H120, but it had acquired hemagglutination activity from NDV. Vaccination of SPF chickens with the R-H120-HN/5a virus induced a humoral response at a level comparable to that of the LaSota/H120 commercial bivalent vaccine and provided significant protection against challenge with virulent IBV and NDV. In summary, the results of this study indicate that the IBV H120 strain could serve as an effective tool for designing vaccines against IB and other infectious diseases, and the generation of IBV R-H120-HN/5a provides a solid foundation for the development of an effective bivalent vaccine against IBV and NDV. PMID:26873815

  7. Production of Monoclonal Antibodies Against the Challenge Strain of Infectious Laryngotracheitis Virus of Chickens and Their Use in an Indirect Immunofluorescent Diagnostic Test

    Directory of Open Access Journals (Sweden)

    Ferhat Abbas*, James Andreasen1, Rockey Becker1, Masroor Ahmed, M Arif Awan, Abdul Wadood and Anita Sonn1

    2010-07-01

    Full Text Available The objective of the present research was to produce monoclonal antibodies (MCAs against the USDA challenge strain of infectious laryngotracheitis virus and to perform an initial investigation of their use in an indirect immunofluorescence diagnostic test. Fourteen-day old chicken embryo liver cells were grown in tissue culture plates. Confluent monolayers were obtained after 48 hours. Monolayers were infected with the USDA challenge strain of infectious laryngotracheitis virus (ILTV. Cytopethic effect of the virus in the form of syncytial formation and clumping of cells was observed after 24 hours. The virus from the tissue culture flasks was collected and purified using discontinuous sucrose gradient. A clear band of the virus from sucrose gradient was obtained. The refractory index and the density measured were 1.410 and 1.20 g/cm3, respectively. Spectrophotometry of the purified virus showed 68.117 ug/ml of protein and 9.8948 ug/ml of nucleic acid concentration. Spleen cells from immunized mice with pure virus were fused with myeloma cells and hybridomas were obtained after 10 days. Screening was performed using indirect immunofluorescence antibody test (IFAT using rabbit anti-mouse immunoglobulins as secondary antibodies. Three hybridomas, 2D1D8, 2E11G2 and 2C6C7 were found producing antibodies against ILTV. All monoclonal antibodies were of isotype IgM and reacted with different strains of ILTV (ILTV USDA, S 88 00224, 86-1169 in IFAT. None of the monoclonals reacted with Parrot herpesvirus and avian adenovirus 301 in IFAT.

  8. Flow-FISH analysis and isolation of clostridial strains in an anaerobic semi-solid bio-hydrogen producing system by hydrogenase gene target.

    Science.gov (United States)

    Jen, Chang Jui; Chou, Chia-Hung; Hsu, Ping-Chi; Yu, Sian-Jhong; Chen, Wei-En; Lay, Jiunn-Jyi; Huang, Chieh-Chen; Wen, Fu-Shyan

    2007-04-01

    By using hydrogenase gene-targeted polymerase chain reaction (PCR) and reverse transcriptase PCR (RT-PCR), the predominant clostridial hydrogenase that may have contributed to biohydrogen production in an anaerobic semi-solid fermentation system has been monitored. The results revealed that a Clostridium pasteurianum-like hydrogenase gene sequence can be detected by both PCR and RT-PCR and suggested that the bacterial strain possessing this specific hydrogenase gene was dominant in hydrogenase activity and population. Whereas another Clostridium saccharobutylicum-like hydrogenase gene can be detected only by RT-PCR and suggest that the bacterial strain possessing this specific hydrogenase gene may be less dominant in population. In this study, hydrogenase gene-targeted fluorescence in situ hybridization (FISH) and flow cytometry analysis confirmed that only 6.6% of the total eubacterial cells in a hydrogen-producing culture were detected to express the C. saccharobutylicum-like hydrogenase, whereas the eubacteria that expressed the C. pasteurianum-like hydrogenase was 25.6%. A clostridial strain M1 possessing the identical nucleotide sequences of the C. saccharobutylicum-like hydrogenase gene was then isolated and identified as Clostridium butyricum based on 16S rRNA sequence. Comparing to the original inoculum with mixed microflora, either using C. butyricum M1 as the only inoculum or co-culturing with a Bacillus thermoamylovorans isolate will guarantee an effective and even better production of hydrogen from brewery yeast waste. PMID:17277963

  9. Linking Genotype and Phenotype of Saccharomyces cerevisiae Strains Reveals Metabolic Engineering Targets and Leads to Triterpene Hyper-Producers

    DEFF Research Database (Denmark)

    Madsen, Karina Marie; Udatha, Gupta D. B. R. K.; Semba, Saori;

    2011-01-01

    S288C strain, we implemented a strategy for the construction of a beta-amyrin production platform. The genes Erg8, Erg9 and HFA1 contained non-silent SNPs that were computationally analyzed to evaluate the changes that cause in the respective protein structures. Subsequently, Erg8, Erg9 and HFA1...

  10. Testing the discrimination and detection limits of WorldView-2 imagery on a challenging invasive plant target

    Science.gov (United States)

    Robinson, T. P.; Wardell-Johnson, G. W.; Pracilio, G.; Brown, C.; Corner, R.; van Klinken, R. D.

    2016-02-01

    Invasive plants pose significant threats to biodiversity and ecosystem function globally, leading to costly monitoring and management effort. While remote sensing promises cost-effective, robust and repeatable monitoring tools to support intervention, it has been largely restricted to airborne platforms that have higher spatial and spectral resolutions, but which lack the coverage and versatility of satellite-based platforms. This study tests the ability of the WorldView-2 (WV2) eight-band satellite sensor for detecting the invasive shrub mesquite (Prosopis spp.) in the north-west Pilbara region of Australia. Detectability was challenged by the target taxa being largely defoliated by a leaf-tying biological control agent (Gelechiidae: Evippe sp. #1) and the presence of other shrubs and trees. Variable importance in the projection (VIP) scores identified bands offering greatest capacity for discrimination were those covering the near-infrared, red, and red-edge wavelengths. Wavelengths between 400 nm and 630 nm (coastal blue, blue, green, yellow) were not useful for species level discrimination in this case. Classification accuracy was tested on three band sets (simulated standard multispectral, all bands, and bands with VIP scores ≥1). Overall accuracies were comparable amongst all band-sets (Kappa = 0.71-0.77). However, mesquite omission rates were unacceptably high (21.3%) when using all eight bands relative to the simulated standard multispectral band-set (9.5%) and the band-set informed by VIP scores (11.9%). An incremental cover evaluation on the latter identified most omissions to be for objects mapping accuracy of objects >16 m2 allows application for mapping mesquite shrubs and coalesced stands, the former not previously possible, even with 3 m resolution hyperspectral imagery. WV2 imagery offers excellent portability potential for detecting other species where spectral/spatial resolution or coverage has been an impediment. New generation satellite

  11. Testing the discrimination and detection limits of WorldView-2 imagery on a challenging invasive plant target

    Science.gov (United States)

    Robinson, T. P.; Wardell-Johnson, G. W.; Pracilio, G.; Brown, C.; Corner, R.; van Klinken, R. D.

    2016-02-01

    Invasive plants pose significant threats to biodiversity and ecosystem function globally, leading to costly monitoring and management effort. While remote sensing promises cost-effective, robust and repeatable monitoring tools to support intervention, it has been largely restricted to airborne platforms that have higher spatial and spectral resolutions, but which lack the coverage and versatility of satellite-based platforms. This study tests the ability of the WorldView-2 (WV2) eight-band satellite sensor for detecting the invasive shrub mesquite (Prosopis spp.) in the north-west Pilbara region of Australia. Detectability was challenged by the target taxa being largely defoliated by a leaf-tying biological control agent (Gelechiidae: Evippe sp. #1) and the presence of other shrubs and trees. Variable importance in the projection (VIP) scores identified bands offering greatest capacity for discrimination were those covering the near-infrared, red, and red-edge wavelengths. Wavelengths between 400 nm and 630 nm (coastal blue, blue, green, yellow) were not useful for species level discrimination in this case. Classification accuracy was tested on three band sets (simulated standard multispectral, all bands, and bands with VIP scores ≥1). Overall accuracies were comparable amongst all band-sets (Kappa = 0.71-0.77). However, mesquite omission rates were unacceptably high (21.3%) when using all eight bands relative to the simulated standard multispectral band-set (9.5%) and the band-set informed by VIP scores (11.9%). An incremental cover evaluation on the latter identified most omissions to be for objects 16 m2 allows application for mapping mesquite shrubs and coalesced stands, the former not previously possible, even with 3 m resolution hyperspectral imagery. WV2 imagery offers excellent portability potential for detecting other species where spectral/spatial resolution or coverage has been an impediment. New generation satellite sensors are removing barriers

  12. Targeting non-coding RNAs in Plants with the CRISPR-Cas technology is a challenge yet worth accepting

    Directory of Open Access Journals (Sweden)

    Jolly eBasak

    2015-11-01

    Full Text Available Non-coding RNAs (ncRNAs have emerged as versatile master regulator of biological functions in recent years. MicroRNAs (miRNAs are small endogenous ncRNAs of 18-24 nucleotides in length that originates from long self-complementary precursors. Besides their direct involvement in developmental processes, plant miRNAs play key roles in gene regulatory networks and varied biological processes. Alternatively, long ncRNAs (lncRNAs are a large and diverse class of transcribed ncRNAs whose length exceed that of 200 nucleotides. Plant lncRNAs are transcribed by different RNA polymerases, showing diverse structural features. Plant lncRNAs also are important regulators of gene expression in diverse biological processes. There has been a breakthrough in the technology of genome editing, the CRISPR-Cas9 (clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 technology, in the last decade. CRISPR loci are transcribed into ncRNA and eventually form a functional complex with Cas9 and further guide the complex to cleave complementary invading DNA. The CRISPR-Cas technology has been successfully applied in model plants such as Arabidopsis and tobacco and important crops like wheat, maize and rice. However, all these studies are focused on protein coding genes. Information about targeting non-coding genes is scarce. Hitherto, the CRISPR-Cas technology has been exclusively used in vertebrate systems to engineer miRNA/lncRNAs, but it is still relatively unexplored in plants. While briefing miRNAs, lncRNAs and applications of the CRISPR-Cas technology in human and animals, this review essentially elaborates several strategies to overcome the challenges of applying the CRISPR-Cas technology in editing ncRNAs in plants and the future perspective of this field.

  13. A standardised challenge model with an enterotoxigenic F4+ Escherichia coli strain in piglets assessing clinical traits and faecal shedding of fae and est-II toxin genes.

    Science.gov (United States)

    Spitzer, Franz; Vahjen, Wilfried; Pieper, Robert; Martinez-Vallespin, Beatriz; Zentek, Jürgen

    2014-12-01

    This study evaluated the effect of five feed additives on post weaning diarrhoea (PWD) in piglets challenged 3 d after weaning with an enterotoxigenic Escherichia coli strain (ETEC). In three experimental runs, a total of 84 piglets was weaned at 21 days of age and randomly assigned to seven treatments. As dietary treatment, piglets were fed a basal diet or diets with addition of bovine colostrum (0.2%), pineapple stem extract containing bromelain (0.2%), an autolysed yeast preparation (Saccharomyces cerevisiae) (0.1%), a combination of organic acids (0.7%) and a phytogenic product with thyme essential oil (0.015%). A porcine ETEC, serotype O149:K91:K88ac was given twice via oral infection on day 3 after weaning at 10(10) colony forming units/animal. One group of piglets was fed the basal diet without ETEC challenge. Traits included clinical sores, body temperature, faecal scoring and determination of faecal dry matter and the shedding of fae and est-II ETEC toxin genes. After weaning, non-challenged control piglets did not show signs of diarrhoea or impaired health, while the majority of infected piglets had a drop in body temperature, signs of diarrhoea and impaired general health. Mortality, the decrease of faecal dry matter and shedding of the toxin genes fae and est-II were not affected by the different additives. In conclusion, the ETEC challenge model induced distinct clinical signs of PWD in piglets, but the tested feed additives had no preventive effect under these conditions. PMID:25313936

  14. Non-target trials with Pseudomonas fluorescens strain CL145A, a lethal control agent of dreissenid mussels (Bivalvia: Dreissenidae)

    OpenAIRE

    Molloy, Daniel P.; Denise A. Mayer; Michael J. Gaylo; Burlakova, Lyubov E.; Karatayev, Alexander Y.; Kathleen T. Presti; Paul M. Sawyko; John T. Morse; Eric A. Paul

    2013-01-01

    In an effort to develop an efficacious and environmentally safe method for managing zebra mussels (Dreissena polymorpha) and quaggamussels (Dreissena rostriformis bugensis), we initiated a research project investigating the potential use of bacteria and their naturalmetabolic products as biocontrol agents. This project resulted in the discovery of an environmental isolate lethal to dreissenid mussels,Pseudomonas fluorescens strain CL145A (Pf-CL145A). In previous published reports we have demo...

  15. A rhizosphere-associated symbiont, Photobacterium spp. strain MELD1, and its targeted synergistic activity for phytoprotection against mercury.

    Science.gov (United States)

    Mathew, Dony Chacko; Ho, Ying-Ning; Gicana, Ronnie Gicaraya; Mathew, Gincy Marina; Chien, Mei-Chieh; Huang, Chieh-Chen

    2015-01-01

    Though heavy metal such as mercury is toxic to plants and microorganisms, the synergistic activity between them may offer benefit for surviving. In this study, a mercury-reducing bacterium, Photobacterium spp. strain MELD1, with an MIC of 33 mg x kg(-1) mercury was isolated from a severely mercury and dioxin contaminated rhizosphere soil of reed (Phragmites australis). While the whole genome sequencing of MELD1 confirmed the presence of a mer operon, the mercury reductase MerA gene showed 99% sequence identity to Vibrio shilloni AK1 and implicates its route resulted from the event of horizontal gene transfer. The efficiency of MELD1 to vaporize mercury (25 mg x kg(-1), 24 h) and its tolerance to toxic metals and xenobiotics such as lead, cadmium, pentachlorophenol, pentachloroethylene, 3-chlorobenzoic acid, 2,3,7,8-tetrachlorodibenzo-p-dioxin and 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin is promising. Combination of a long yard bean (Vigna unguiculata ssp. Sesquipedalis) and strain MELD1 proved beneficial in the phytoprotection of mercury in vivo. The effect of mercury (Hg) on growth, distribution and tolerance was examined in root, shoot, leaves and pod of yard long bean with and without the inoculation of strain MELD1. The model plant inoculated with MELD1 had significant increases in biomass, root length, seed number, and increased mercury uptake limited to roots. Biolog plate assay were used to assess the sole-carbon source utilization pattern of the isolate and Indole-3-acetic acid (IAA) productivity was analyzed to examine if the strain could contribute to plant growth. The results of this study suggest that, as a rhizosphere-associated symbiont, the synergistic activity between the plant and MELD1 can improve the efficiency for phytoprotection, phytostabilization and phytoremediation of mercury. PMID:25816328

  16. A rhizosphere-associated symbiont, Photobacterium spp. strain MELD1, and its targeted synergistic activity for phytoprotection against mercury.

    Directory of Open Access Journals (Sweden)

    Dony Chacko Mathew

    Full Text Available Though heavy metal such as mercury is toxic to plants and microorganisms, the synergistic activity between them may offer benefit for surviving. In this study, a mercury-reducing bacterium, Photobacterium spp. strain MELD1, with an MIC of 33 mg x kg(-1 mercury was isolated from a severely mercury and dioxin contaminated rhizosphere soil of reed (Phragmites australis. While the whole genome sequencing of MELD1 confirmed the presence of a mer operon, the mercury reductase MerA gene showed 99% sequence identity to Vibrio shilloni AK1 and implicates its route resulted from the event of horizontal gene transfer. The efficiency of MELD1 to vaporize mercury (25 mg x kg(-1, 24 h and its tolerance to toxic metals and xenobiotics such as lead, cadmium, pentachlorophenol, pentachloroethylene, 3-chlorobenzoic acid, 2,3,7,8-tetrachlorodibenzo-p-dioxin and 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin is promising. Combination of a long yard bean (Vigna unguiculata ssp. Sesquipedalis and strain MELD1 proved beneficial in the phytoprotection of mercury in vivo. The effect of mercury (Hg on growth, distribution and tolerance was examined in root, shoot, leaves and pod of yard long bean with and without the inoculation of strain MELD1. The model plant inoculated with MELD1 had significant increases in biomass, root length, seed number, and increased mercury uptake limited to roots. Biolog plate assay were used to assess the sole-carbon source utilization pattern of the isolate and Indole-3-acetic acid (IAA productivity was analyzed to examine if the strain could contribute to plant growth. The results of this study suggest that, as a rhizosphere-associated symbiont, the synergistic activity between the plant and MELD1 can improve the efficiency for phytoprotection, phytostabilization and phytoremediation of mercury.

  17. Conserved sequences in the current strains of HIV-1 subtype A in Russia are effectively targeted by artificial RNAi in vitro.

    Science.gov (United States)

    Tchurikov, Nickolai A; Fedoseeva, Daria M; Gashnikova, Natalya M; Sosin, Dmitri V; Gorbacheva, Maria A; Alembekov, Ildar R; Chechetkin, Vladimir R; Kravatsky, Yuri V; Kretova, Olga V

    2016-05-25

    Highly active antiretroviral therapy has greatly reduced the morbidity and mortality of AIDS. However, many of the antiretroviral drugs are toxic with long-term use, and all currently used anti-HIV agents generate drug-resistant mutants. Therefore, there is a great need for new approaches to AIDS therapy. RNAi is a powerful means of inhibiting HIV-1 production in human cells. We propose to use RNAi for gene therapy of HIV/AIDS. Previously we identified a number of new biologically active siRNAs targeting several moderately conserved regions in HIV-1 transcripts. Here we analyze the heterogeneity of nucleotide sequences in three RNAi targets in sequences encoding the reverse transcriptase and integrase domains of current isolates of HIV-1 subtype A in Russia. These data were used to generate genetic constructs expressing short hairpin RNAs 28-30-bp in length that could be processed in cells into siRNAs. After transfection of the constructs we observed siRNAs that efficiently attacked the selected targets. We expect that targeting several viral genes important for HIV-1 reproduction will help overcome the problem of viral adaptation and will prevent the appearance of RNAi escape mutants in current virus strains, an important feature of gene therapy of HIV/AIDS. PMID:26947394

  18. Selection of Vibrio harveyi-resistant Litopenaeus vannamei via a three-round challenge selection with a pathogenic strain of V. harveyi.

    Science.gov (United States)

    Huang, Hai-Hong; Liu, Xiao-Lin; Xiang, Jian-Hai; Wang, Ping

    2013-08-01

    To obtain Vibrio harveyi-resistant Litopenaeus vannamei shrimp used for study on immune response of shrimp avoid vibriosis, a three-round challenge selection procedure was applied. In this procedure, resistant shrimp were selected gradually via three rounds challenge experiment with a pathogenic strain of V. harveyi at a median and controllable lethal dose of 96-h LD50 (the median lethal dose). After this procedure, the cumulative mortality of selected shrimp during 96 h after injection of V. harveyi at 2.0 × 10(6) cfu shrimp(-1) significantly decreased from 93.3% to 26.7%, the hours of beginning of death and the hours of attaining of the maximum cumulative mortality of shrimp prolonged from 4 h and 10 h to 8 h and 24 h, respectively. The LD50 of 6 h, 12 h, 24 h, 48 h and 96 h of selected shrimp significantly increased to 1.4 ± 0.1 × 10(7) (p < 0.01), 5.5 ± 0.4 × 10(6) (p < 0.01), 3.1 ± 0.2 × 10(6) (p < 0.01), 2.7 ± 0.1 × 10(6) (p < 0.01) and 2.7 ± 0.1 × 10(6) cfu shrimp(-1) (p < 0.01), about 15.9, 15.3, 9.4, 10.0 and 10.4 times of that of normal shrimp, respectively. In conclusion, the resistance of shrimp to Vibrio significantly increased after the three-round challenge selection procedure. PMID:23665547

  19. Humoral immune response of C57Bl/6j and BALB/c mice immunized with irradiated tachyzoites of Toxoplasma gondii RH strain and oral challenge with ME-49 strain

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez Galisteo Junior, Andres [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Centro de Biotecnologia; Instituto de Medicina Tropical de Sao Paulo, Sao Paulo, SP (Brazil). Lab. de Protozoologia; E-mail: galisteo@usp.br; Zorgi, Nahiara Esteves; Andrade Junior, Heitor Franco de [Instituto de Medicina Tropical de Sao Paulo, Sao Paulo, SP (Brazil). Lab. de Protozoologia; Alves, Janaina Baptista; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Centro de Biotecnologia; Hiramoto, Roberto Mitsuyoshi [instituto Adolfo Lutz, Sao Paulo, SP (Brazil)

    2007-07-01

    Toxoplasmosis, a prevalent widespread infection in man and animals, is mainly transmitted by oral route, through ingestion of oocysts from water and food contaminated with cat feces or infected animal tissue cysts in undercooked meat. Vaccine development implies in effective intestinal immunity, the first site of parasite entry. Radiation (255 Gy/{sup 60}Co) sterilized T. gondii RH strain tachyzoites (RST) induced significant protection when parentally administered, similar to chronically infected and acute disease protected animal. We study the humoral immune response in C57Bl/6j and BALB/c mice immunized with 10{sup 7} RST, by oral (with aluminium hydroxide 3%) or parenteral 3 biweekly administrations. T. gondii antigens specific ELISA for IgG, IgA, IgG1, IgG2a and IgG2b detection was performed in weekly blood samples during immunization. Also we evaluate of the intestinal epithelial of immunized mice the integrity of the radiated parasites by electronic microscopy. After 2 weeks, immunized and control animals were challenged with 10 cysts of ME-49 strain p.o. Protection was determined at the 30th day by brain cyst counting. As it was possible to observe in the intestinal mucosal, the aluminium hydroxide seems to maintain unchanged the parasite morphology and its mechanisms of invasion, probably due to keeping it safe from extreme pH condition of stomach. All immunized groups presented significant protection when challenged with ME-49; however, BALB/c mice showed better protection levels, with only one positive animal on brain microscopic analysis. IgG production in the serum of the animals was higher in groups immunized by i.p route, however, IgA and IgG1 levels were higher in BALB/c mice immunized by oral route. This higher protection found in BALB/c group could probably also be related to the Th2 response, demonstrated by higher IgG1 levels. All these data provide insights in oral immunization schedules for toxoplasmosis prevention, suggesting that oral

  20. Humoral immune response of C57Bl/6j and BALB/c mice immunized with irradiated tachyzoites of Toxoplasma gondii RH strain and oral challenge with ME-49 strain

    International Nuclear Information System (INIS)

    Toxoplasmosis, a prevalent widespread infection in man and animals, is mainly transmitted by oral route, through ingestion of oocysts from water and food contaminated with cat feces or infected animal tissue cysts in undercooked meat. Vaccine development implies in effective intestinal immunity, the first site of parasite entry. Radiation (255 Gy/60Co) sterilized T. gondii RH strain tachyzoites (RST) induced significant protection when parentally administered, similar to chronically infected and acute disease protected animal. We study the humoral immune response in C57Bl/6j and BALB/c mice immunized with 107 RST, by oral (with aluminium hydroxide 3%) or parenteral 3 biweekly administrations. T. gondii antigens specific ELISA for IgG, IgA, IgG1, IgG2a and IgG2b detection was performed in weekly blood samples during immunization. Also we evaluate of the intestinal epithelial of immunized mice the integrity of the radiated parasites by electronic microscopy. After 2 weeks, immunized and control animals were challenged with 10 cysts of ME-49 strain p.o. Protection was determined at the 30th day by brain cyst counting. As it was possible to observe in the intestinal mucosal, the aluminium hydroxide seems to maintain unchanged the parasite morphology and its mechanisms of invasion, probably due to keeping it safe from extreme pH condition of stomach. All immunized groups presented significant protection when challenged with ME-49; however, BALB/c mice showed better protection levels, with only one positive animal on brain microscopic analysis. IgG production in the serum of the animals was higher in groups immunized by i.p route, however, IgA and IgG1 levels were higher in BALB/c mice immunized by oral route. This higher protection found in BALB/c group could probably also be related to the Th2 response, demonstrated by higher IgG1 levels. All these data provide insights in oral immunization schedules for toxoplasmosis prevention, suggesting that oral vaccines could be

  1. miRNA-133 augments coelomocyte phagocytosis in bacteria-challenged Apostichopus japonicus via targeting the TLR component of IRAK-1 in vitro and in vivo

    OpenAIRE

    Meng Lu; Peng-Juan Zhang; Cheng-Hua Li; Zhi-Meng Lv; Wei-Wei Zhang; Chun-Hua Jin

    2015-01-01

    In this study, we explored the potential roles of miRNA-133 in regulating TLR pathways in the sea cucumber Apostichopus japonicus. Target screening of RNA-Seq data successfully identified interleukin-1 receptor-associated kinase (AjIRAK−1) as a putative target of miR-133. This result was further validated by negative expression profiles in Vibrio splendidus-challenged coelomocytes and lipopolysaccharide (LPS)-exposed cell cultures. HEK-293T cells transfected with a dual-luciferase reporter fu...

  2. Target experiments with light-ion beams at KALIF: Measurements of the dynamic strength and spallation threshold of metals at high strain rates

    International Nuclear Information System (INIS)

    In target experiments performed at the KfK KALIF facility, pulsed proton beams of about 20 kJ pulse energy have been used to ablatively accelerate flyer foils of macroscopic lateral dimensions (∼0.5 cm) to very high velocities (up to >10 km/s) generating impact loadings in plane target samples. An ORVIS-type velocity spectrometer has been set up and synchronized with the ion-beam driver to investigate the dynamic response of solid target matter with high accuracy (up to 1%) and very high time resolution (up to 200 ps). In proof-of-principle experiments the KALIF-ORVIS facility has been used to measure the dynamic strength solid matter to tensile fracture up to very high strain rates of 108 s-1. The materials under investigation have been single and polycrystalline samples of molybdenum, aluminum, and sapphire. The experiments have verified the advantageous perspectives of high-power light-ion drivers for experimental dynamic matter research

  3. Tuberculosis: opportunities and challenges for the 90–90–90 targets in HIV-infected children

    OpenAIRE

    Helena Rabie; Lisa Frigati; Hesseling, Anneke C; Garcia-Prats, Anthony J.

    2015-01-01

    Introduction: In 2014 the Joint United Nations Programme on HIV/AIDS defined the ambitious 90–90–90 targets for 2020, in which 90% of people living with HIV must be diagnosed, 90% of those diagnosed should be on sustained therapy and 90% of those on therapy should have an undetectable viral load. Children are considered to be a key focus population for these targets. This review will highlight key components of the epidemiology, prevention and treatment of tuberculosis (TB) in HIV-infected ch...

  4. MiR-31 modulates coelomocytes ROS production via targeting p105 in Vibrio splendidus challenged sea cucumber Apostichopus japonicus in vitro and in vivo.

    Science.gov (United States)

    Lu, Meng; Zhang, Pengjuan; Li, Chenghua; Zhang, Weiwei; Jin, Chunhua; Han, Qingxi

    2015-08-01

    MiR-31 is a critical regulator of gene expression in many pathogenic processes in vertebrates. In this study, we identified p105 as a novel target of miR-31 in Apostichopus japonicus and investigated their regulatory roles in vitro and in vivo. The negative expression profiles between miR-31 and Ajp105 were detected in both LPS-exposed primary coelomocytes and Vibrio splendidus-challenged sea cucumber. Co-infection miR-31 mimics significantly depressed the expression of Ajp105 and increased ROS production in vitro. In contrast, miR-31 inhibitor significantly elevated the expression of Ajp105 and decreased ROS level. Consistently, miR-31 over-expression or Ajp105 silencing in vivo both greatly promoted ROS accumulation. Taken together, our findings confirmed that miR-31 could modulate respiratory burst via targeting Ajp105 during sea cucumber pathological development. PMID:25917973

  5. The clinical-grade 42-kilodalton fragment of merozoite surface protein 1 of Plasmodium falciparum strain FVO expressed in Escherichia coli protects Aotus nancymai against challenge with homologous erythrocytic-stage parasites.

    Science.gov (United States)

    Darko, Christian A; Angov, Evelina; Collins, William E; Bergmann-Leitner, Elke S; Girouard, Autumn S; Hitt, Stacy L; McBride, Jana S; Diggs, Carter L; Holder, Anthony A; Long, Carole A; Barnwell, John W; Lyon, Jeffrey A

    2005-01-01

    A 42-kDa fragment from the C terminus of major merozoite surface protein 1 (MSP1) is among the leading malaria vaccine candidates that target infection by asexual erythrocytic-stage malaria parasites. The MSP1(42) gene fragment from the Vietnam-Oak Knoll (FVO) strain of Plasmodium falciparum was expressed as a soluble protein in Escherichia coli and purified according to good manufacturing practices. This clinical-grade recombinant protein retained some important elements of correct structure, as it was reactive with several functional, conformation-dependent monoclonal antibodies raised against P. falciparum malaria parasites, it induced antibodies (Abs) that were reactive to parasites in immunofluorescent Ab tests, and it induced strong growth and invasion inhibitory antisera in New Zealand White rabbits. The antigen quality was further evaluated by vaccinating Aotus nancymai monkeys and challenging them with homologous P. falciparum FVO erythrocytic-stage malaria parasites. The trial included two control groups, one vaccinated with the sexual-stage-specific antigen of Plasmodium vivax, Pvs25, as a negative control, and the other vaccinated with baculovirus-expressed MSP1(42) (FVO) as a positive control. Enzyme-linked immunosorbent assay (ELISA) Ab titers induced by E. coli MSP1(42) were significantly higher than those induced by the baculovirus-expressed antigen. None of the six monkeys that were vaccinated with the E. coli MSP1(42) antigen required treatment for uncontrolled parasitemia, but two required treatment for anemia. Protective immunity in these monkeys correlated with the ELISA Ab titer against the p19 fragment and the epidermal growth factor (EGF)-like domain 2 fragment of MSP1(42), but not the MSP1(42) protein itself or the EGF-like domain 1 fragment. Soluble MSP1(42) (FVO) expressed in E. coli offers excellent promise as a component of a vaccine against erythrocytic-stage falciparum malaria. PMID:15618165

  6. A biodiversity indicators dashboard: addressing challenges to monitoring progress towards the Aichi biodiversity targets using disaggregated global data.

    Directory of Open Access Journals (Sweden)

    Xuemei Han

    Full Text Available Recognizing the imperiled status of biodiversity and its benefit to human well-being, the world's governments committed in 2010 to take effective and urgent action to halt biodiversity loss through the Convention on Biological Diversity's "Aichi Targets". These targets, and many conservation programs, require monitoring to assess progress toward specific goals. However, comprehensive and easily understood information on biodiversity trends at appropriate spatial scales is often not available to the policy makers, managers, and scientists who require it. We surveyed conservation stakeholders in three geographically diverse regions of critical biodiversity concern (the Tropical Andes, the African Great Lakes, and the Greater Mekong and found high demand for biodiversity indicator information but uneven availability. To begin to address this need, we present a biodiversity "dashboard"--a visualization of biodiversity indicators designed to enable tracking of biodiversity and conservation performance data in a clear, user-friendly format. This builds on previous, more conceptual, indicator work to create an operationalized online interface communicating multiple indicators at multiple spatial scales. We structured this dashboard around the Pressure-State-Response-Benefit framework, selecting four indicators to measure pressure on biodiversity (deforestation rate, state of species (Red List Index, conservation response (protection of key biodiversity areas, and benefits to human populations (freshwater provision. Disaggregating global data, we present dashboard maps and graphics for the three regions surveyed and their component countries. These visualizations provide charts showing regional and national trends and lay the foundation for a web-enabled, interactive biodiversity indicators dashboard. This new tool can help track progress toward the Aichi Targets, support national monitoring and reporting, and inform outcome-based policy-making for the

  7. A biodiversity indicators dashboard: addressing challenges to monitoring progress towards the Aichi biodiversity targets using disaggregated global data.

    Science.gov (United States)

    Han, Xuemei; Smyth, Regan L; Young, Bruce E; Brooks, Thomas M; Sánchez de Lozada, Alexandra; Bubb, Philip; Butchart, Stuart H M; Larsen, Frank W; Hamilton, Healy; Hansen, Matthew C; Turner, Will R

    2014-01-01

    Recognizing the imperiled status of biodiversity and its benefit to human well-being, the world's governments committed in 2010 to take effective and urgent action to halt biodiversity loss through the Convention on Biological Diversity's "Aichi Targets". These targets, and many conservation programs, require monitoring to assess progress toward specific goals. However, comprehensive and easily understood information on biodiversity trends at appropriate spatial scales is often not available to the policy makers, managers, and scientists who require it. We surveyed conservation stakeholders in three geographically diverse regions of critical biodiversity concern (the Tropical Andes, the African Great Lakes, and the Greater Mekong) and found high demand for biodiversity indicator information but uneven availability. To begin to address this need, we present a biodiversity "dashboard"--a visualization of biodiversity indicators designed to enable tracking of biodiversity and conservation performance data in a clear, user-friendly format. This builds on previous, more conceptual, indicator work to create an operationalized online interface communicating multiple indicators at multiple spatial scales. We structured this dashboard around the Pressure-State-Response-Benefit framework, selecting four indicators to measure pressure on biodiversity (deforestation rate), state of species (Red List Index), conservation response (protection of key biodiversity areas), and benefits to human populations (freshwater provision). Disaggregating global data, we present dashboard maps and graphics for the three regions surveyed and their component countries. These visualizations provide charts showing regional and national trends and lay the foundation for a web-enabled, interactive biodiversity indicators dashboard. This new tool can help track progress toward the Aichi Targets, support national monitoring and reporting, and inform outcome-based policy-making for the protection of

  8. A Biodiversity Indicators Dashboard: Addressing Challenges to Monitoring Progress towards the Aichi Biodiversity Targets Using Disaggregated Global Data

    Science.gov (United States)

    Han, Xuemei; Smyth, Regan L.; Young, Bruce E.; Brooks, Thomas M.; Sánchez de Lozada, Alexandra; Bubb, Philip; Butchart, Stuart H. M.; Larsen, Frank W.; Hamilton, Healy; Hansen, Matthew C.; Turner, Will R.

    2014-01-01

    Recognizing the imperiled status of biodiversity and its benefit to human well-being, the world's governments committed in 2010 to take effective and urgent action to halt biodiversity loss through the Convention on Biological Diversity's “Aichi Targets”. These targets, and many conservation programs, require monitoring to assess progress toward specific goals. However, comprehensive and easily understood information on biodiversity trends at appropriate spatial scales is often not available to the policy makers, managers, and scientists who require it. We surveyed conservation stakeholders in three geographically diverse regions of critical biodiversity concern (the Tropical Andes, the African Great Lakes, and the Greater Mekong) and found high demand for biodiversity indicator information but uneven availability. To begin to address this need, we present a biodiversity “dashboard” – a visualization of biodiversity indicators designed to enable tracking of biodiversity and conservation performance data in a clear, user-friendly format. This builds on previous, more conceptual, indicator work to create an operationalized online interface communicating multiple indicators at multiple spatial scales. We structured this dashboard around the Pressure-State-Response-Benefit framework, selecting four indicators to measure pressure on biodiversity (deforestation rate), state of species (Red List Index), conservation response (protection of key biodiversity areas), and benefits to human populations (freshwater provision). Disaggregating global data, we present dashboard maps and graphics for the three regions surveyed and their component countries. These visualizations provide charts showing regional and national trends and lay the foundation for a web-enabled, interactive biodiversity indicators dashboard. This new tool can help track progress toward the Aichi Targets, support national monitoring and reporting, and inform outcome-based policy-making for the

  9. CD71 targeting boosts immunogenicity of sublingually delivered influenza haemagglutinin antigen and protects against viral challenge in mice.

    Science.gov (United States)

    Mann, Jamie F S; Tregoning, John S; Aldon, Yoann; Shattock, Robin J; McKay, Paul F

    2016-06-28

    The delivery of vaccines to the sublingual mucosa is an attractive prospect due to the ease and acceptability of such an approach. However, novel adjuvant and delivery approaches are required to optimally vaccinate at this site. We have previously shown that conjugation of protein antigen to the iron transport molecule, transferrin, can significantly enhance mucosal immune responses. We tested whether conjugating influenza haemagglutinin to transferrin could improve the immune response to sublingually delivered antigen. Transferrin conjugated haemagglutinin induced a significant antibody and T cell response in both naïve animals and previously immunized animals. The immune response generated was able to protect mice against influenza virus challenge. Sublingually administered antigen dispersed more widely through the gastro-intestinal tract than intranasally delivered antigen and transferrin conjugation had a more marked effect on sublingually delivered antigen than intranasal immunisation. From these studies we conclude that transferrin conjugation of antigen is effective at boosting immune responses to sublingually delivered antigen and may be an attractive approach for influenza vaccines, particularly when mass campaigns are required. PMID:27094605

  10. Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss

    Directory of Open Access Journals (Sweden)

    Selma Olsson Åkefeldt

    2013-01-01

    Full Text Available Rheumatoid arthritis (RA and Langerhans cell histiocytosis (LCH are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC, and, especially, regulating their half-life and fusion, is a challenge. Indeed, these myeloid cells display pathogenic roles in both diseases and may be an important source of precursors for differentiation of osteoclasts, the bone-resorbing multinucleated giant cells. We have recently documented that the proinflammatory cytokine IL-17A regulates long-term survival of DC by inducing BCL2A1 expression, in addition to the constitutive MCL1 expression. We summarize bibliography of the BCL2 family members and their therapeutic targeting, with a special emphasis on MCL1 and BCL2A1, discussing their potential impact on RA and LCH. Our recent knowledge in the survival pathway, which is activated to perform DC fusion in the presence of IL-17A, suggests that targeting MCL1 and BCL2A1 in infiltrating DC may affect the clinical outcomes in RA and LCH. The development of new therapies, interfering with MCL1 and BCL2A1 expression, to target long-term surviving inflammatory DC should be translated into preclinical studies with the aim to increase the well-being of patients with RA and LCH.

  11. miRNA-133 augments coelomocyte phagocytosis in bacteria-challenged Apostichopus japonicus via targeting the TLR component of IRAK-1 in vitro and in vivo.

    Science.gov (United States)

    Lu, Meng; Zhang, Peng-Juan; Li, Cheng-Hua; Lv, Zhi-Meng; Zhang, Wei-Wei; Jin, Chun-Hua

    2015-01-01

    In this study, we explored the potential roles of miRNA-133 in regulating TLR pathways in the sea cucumber Apostichopus japonicus. Target screening of RNA-Seq data successfully identified interleukin-1 receptor-associated kinase (AjIRAK-1) as a putative target of miR-133. This result was further validated by negative expression profiles in Vibrio splendidus-challenged coelomocytes and lipopolysaccharide (LPS)-exposed cell cultures. HEK-293T cells transfected with a dual-luciferase reporter fused to the 3'UTR of wild-type or mutant AjIRAK-1 exhibited a 52.9% reduction in luciferase activity (p < 0.01) compared to controls. Co-infection with a miR-133 mimics or a specific siRNA targeting AjIRAK-1 significantly repressed the mRNA and protein expression levels of AjIRAK-1 and its downstream molecules, such as AjTRAF6 and Ajp105, in primary coelomocytes. In contrast, a miR-133 inhibitor significantly increased the expression of these TLR pathway members. The injection of miR-133 agomir or AjIRAK-1 siRNA into sea cucumbers not only decreased the expression of AjIRAK-1 and its downstream molecules but also significantly increased V. splendidus coelomocyte phagocytosis. All of the present data provide direct evidence that miR-133 is involved in TLR cascade modulation through AjIRAK-1 targeting to promote V. splendidus coelomocyte phagocytosis in these non-model invertebrates. PMID:26223836

  12. Energy and Sustainability: the European challenge of achieving the 2020 targets; Energia y sostenibilidad. El reto Europeo del logro de los objectivos del 2020

    Energy Technology Data Exchange (ETDEWEB)

    Bachiller Araque, J.

    2010-07-01

    The European Union and the energy sector should particularly face up to the triple challenge of increasing the security of supply, de carbonizing its production system and improving the competitiveness of its business network. Achieving the above objectives will involve relevant changes in the way to satisfy the primary energy demand and the electricity generation mix, the development and incorporation of new technologies, as well as the full completion of the internal energy market. Moreover, achieving the 20 targets in 2020 and perhaps a greater requirement on one of them will require increased energy efficiency in the whole chain, from production to consumption, as well as policies and initiatives on energy saving which are consistent with the maintenance of the current levels of welfare. (Author) 27 refs.

  13. The challenge of reducing scientific complexity for different target groups (without losing the essence) - experiences from interdisciplinary audio-visual media production

    Science.gov (United States)

    Hezel, Bernd; Broschkowski, Ephraim; Kropp, Jürgen

    2013-04-01

    The Climate Media Factory originates from an interdisciplinary media lab run by the Film and Television University "Konrad Wolf" Potsdam-Babelsberg (HFF) and the Potsdam Institute for Climate Impact Research (PIK). Climate scientists, authors, producers and media scholars work together to develop media products on climate change and sustainability. We strive towards communicating scientific content via different media platforms reconciling the communication needs of scientists and the audience's need to understand the complexity of topics that are relevant in their everyday life. By presenting four audio-visual examples, that have been designed for very different target groups, we show (i) the interdisciplinary challenges during the production process and the lessons learnt and (ii) possibilities to reach the required degree of simplification without the need for dumbing down the content. "We know enough about climate change" is a short animated film that was produced for the German Agency for International Cooperation (GIZ) for training programs and conferences on adaptation in the target countries including Indonesia, Tunisia and Mexico. "Earthbook" is a short animation produced for "The Year of Science" to raise awareness for the topics of sustainability among digital natives. "What is Climate Engineering?". Produced for the Institute for Advanced Sustainability Studies (IASS) the film is meant for an informed and interested public. "Wimmelwelt Energie!" is a prototype of an iPad application for children from 4-6 years of age to help them learn about different forms of energy and related greenhouse gas emissions.

  14. Nuclear medicine and oncology. Hopes and challenging issues of drugs development: the usefulness of positron emission tomography (PET). An application to targeted therapy

    International Nuclear Information System (INIS)

    Thanks to breakthroughs in drug design, new kinds of treatment in oncology have been developed. These new molecules target usually a precise molecular pathway proved to be involved in the development of a malignant disease. This led to the concept of targeted therapy. Therefore, the accurate selection of patients who may experience a clinical benefit of such treatments, and the way to assess the response are still challenging issues. Molecular imaging with radiolabeled compounds seemed to be a very promising tool, as for example PET with F-18 Fluorodeoxyglucose (FDG) which allows to assess and to predict the response to a tyrosine kinase inhibitors more efficiently than conventional imaging tools. FDG is only a surrogate marker of cell proliferation. New F18 radiolabeled molecules provide more specific information about tumor biology, such as receptor expression, DNA and protein synthesis, rate of hypoxia.... The common tools (clinical and radiological assessment) are no longer sufficient to predict the clinical efficacy of these new drugs. Molecular imaging should be added in the design of clinical trials in order to detect earlier pharmaco-dynamic effects, to select responding patients and to provide proofs of efficacy of these non-cytotoxic compounds. Molecular imaging databases have to be created and cross-matched to tumor sample collections, providing consequently new 'dynamic' pathological resources. This requires that all these new F18 radiolabeled molecules have to be readily available and easy to be implemented in clinical trials. (author)

  15. Genetic inactivation of mitochondria-targeted redox enzyme p66ShcA preserves neuronal viability and mitochondrial integrity in response to oxidative challenges

    Directory of Open Access Journals (Sweden)

    Michael eForte

    2012-07-01

    Full Text Available Mitochondria are essential to neuronal viability and function due to their roles in ATP production, intracellular calcium regulation, and activation of apoptotic pathways. Accordingly, mitochondrial dysfunction has been indicated in a wide variety of neurodegenerative diseases, including Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis, stroke and multiple sclerosis (MS. Recent evidence points to the permeability transition pore (PTP as a key player in mitochondrial dysfunction in these diseases, in which pathologic opening leads to mitochondrial swelling, rupture, release of cytochrome c, and neuronal death. Reactive oxygen species (ROS, which are inducers of PTP opening, have been prominently implicated in the progression of many of these neurodegenerative diseases. In this context, inactivation of a mitochondria-targeted redox enzyme p66ShcA (p66 has been recently shown to prevent the neuronal cell death leading to axonal severing in the murine model of MS, experimental autoimmune encephalomyelitis (EAE. To further characterize the response of neurons lacking p66, we assessed their reaction to treatment with oxidative stressors implicated in neurodegenerative pathways. Specifically, p66-knockout (p66-KO and wild-type (WT neurons were treated with hydrogen peroxide (H2O2 and nitric oxide (NO, and assessed for cell viability and changes in mitochondrial properties, including morphology and ROS production. The results showed that p66-KO neurons had greater survival following treatment with oxidative stressors and generated less ROS when compared to WT neurons. Correspondingly, mitochondria in p66-KO neurons showed diminished morphological changes in response to these challenges. Overall, these findings highlight the importance of developing mitochondria-targeted therapeutics for neurodegenerative disorders, and emphasize p66, mitochondrial ROS, and the PTP as key targets for maintaining mitochondrial and neuronal

  16. Vaccination of elk (Cervus canadensis with Brucella abortus strain RB51 overexpressing superoxide dismutase and glycosyltransferase genes does not induce adequate protection against experimental Brucella abortus challenge

    Directory of Open Access Journals (Sweden)

    Pauline eNol

    2016-02-01

    Full Text Available In recent years, elk (Cervus canadensis have been implicated as the source of Brucella abortus infection for numerous cattle herds in the Greater Yellowstone Area. In the face of environmental and ecological changes on the landscape, the range of infected elk is expanding. Consequently, the development of effective disease management strategies for wild elk herds is of utmost importance, not only for the prevention of reintroduction of brucellosis to cattle, but also for the overall health of the Greater Yellowstone Area elk populations. In two studies, we evaluated the efficacy of B. abortus strain RB51 over-expressing superoxide dismutase and glycosytransferase for protecting elk from infection and disease caused by B. abortus after experimental infection with a virulent B. abortus strain. Our data indicate that the recombinant vaccine does not protect elk against brucellosis. Further work is needed for development of an effective brucellosis vaccine for use in elk

  17. Challenge pools of hepatitis C virus genotypes 1-6 prototype strains: replication fitness and pathogenicity in chimpanzees and human liver-chimeric mouse models

    DEFF Research Database (Denmark)

    Bukh, Jens; Meuleman, Philip; Tellier, Raymond;

    2010-01-01

    Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1-6 and determined the infectivity titer of acute-phase plasma pools in additional...... resource for studies of HCV molecular virology and for studies of pathogenesis, protective immunity, and vaccine efficacy in vivo....

  18. RRR for NNN-a rapid research response for the Neglected Tropical Disease NGDO Network: a novel framework to challenges faced by the global programs targeting neglected tropical diseases.

    Science.gov (United States)

    Toledo, Chelsea E; Jacobson, Julie; Wainwright, Emily C; Ottesen, Eric A; Lammie, Patrick J

    2016-03-01

    While global programs targeting the control or elimination of five of the neglected tropical diseases (NTDs)-lymphatic filariasis, onchocerciasis, soil-transmitted helminthiasis, schistosomiasis and trachoma-are well underway, they still face many operational challenges. Because of the urgency of 2020 program targets, the Bill & Melinda Gates Foundation and the U.S. Agency for International Development devised a novel rapid research response (RRR) framework to engage national programs, researchers, implementers and WHO in a Coalition for Operational Research on NTDs. After 2 years, this effort has succeeded as an important basis for the research response to programmatic challenges facing NTD programs. PMID:26940303

  19. RRR for NNN—a rapid research response for the Neglected Tropical Disease NGDO Network: a novel framework to challenges faced by the global programs targeting neglected tropical diseases

    Science.gov (United States)

    Toledo, Chelsea E.; Jacobson, Julie; Wainwright, Emily C.; Ottesen, Eric A.; Lammie, Patrick J.

    2016-01-01

    While global programs targeting the control or elimination of five of the neglected tropical diseases (NTDs)—lymphatic filariasis, onchocerciasis, soil-transmitted helminthiasis, schistosomiasis and trachoma—are well underway, they still face many operational challenges. Because of the urgency of 2020 program targets, the Bill & Melinda Gates Foundation and the U.S. Agency for International Development devised a novel rapid research response (RRR) framework to engage national programs, researchers, implementers and WHO in a Coalition for Operational Research on NTDs. After 2 years, this effort has succeeded as an important basis for the research response to programmatic challenges facing NTD programs. PMID:26940303

  20. Identification of novel drug targets in HpB38, HpP12, HpG27, Hpshi470, HpSJM180 strains of Helicobacter pylori : an in silico approach for therapeutic intervention.

    Science.gov (United States)

    Neelapu, Nageswara Rao Reddy; Pavani, T

    2013-05-01

    Helicobacter species colonizes the stomach and are associated with the development of gastritis disease. Drugs for treatment of Helicobacter infection relieve pain or gastritis symptoms but they are not targeted specifically to Helicobacter pylori. Therefore, there is dire need for discovery of new drug targets and drugs for the treatment of H. pylori. The main objective of this study is to screen the potential drug targets by in silico analysis for the potent strains of H. pylori which include HpB38, HpP12, HpG27, Hpshi470 and HpSJM180. Genome and metabolic pathways of pathogen H. pylori and the host Homosapien sapiens are compared and genes which were unique to H. pylori were filtered and catalogued. These unique genes were subjected to gene property analysis to identify the potentiality of the drug targets. Among the total number of genes analysed in different strains of H. pylori nearly 558, 569, 539, 569, 567 number of genes in HpB38, HpP12, HpG27, Hpshi470 and HpSJM180 found qualified as unique molecules and among them 17 qualified as potential drug targets. Membrane fusion protein of hefABC efflux system, 50 S ribosomal protein L33, Hydrogenase expression protein/formation of HypD, Cag pathogenecity island protein X, Apolipoprotein N acyl transferase, DNA methyalse, Histone like binding protein, Peptidoglycan-associated lipoprotein OprL were found to be critical drug targets to H. pylori. Three (hefABC efflux system, Hydrogenase expression protein/formation of HypD, Cag pathogenecity island protein X) of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lending credence to our unique approach. PMID:23410125

  1. RRR for NNN—a rapid research response for the Neglected Tropical Disease NGDO Network: a novel framework to challenges faced by the global programs targeting neglected tropical diseases

    OpenAIRE

    Toledo, Chelsea E.; Jacobson, Julie; Wainwright, Emily C.; Eric A Ottesen; Patrick J Lammie

    2016-01-01

    While global programs targeting the control or elimination of five of the neglected tropical diseases (NTDs)—lymphatic filariasis, onchocerciasis, soil-transmitted helminthiasis, schistosomiasis and trachoma—are well underway, they still face many operational challenges. Because of the urgency of 2020 program targets, the Bill & Melinda Gates Foundation and the U.S. Agency for International Development devised a novel rapid research response (RRR) framework to engage national programs, resear...

  2. Humulus lupus Beta-acids Administered Through Water Reduce Clostridium perfringens Challenge Strains in the Chicken Intestinal Tract Midgut and Ceca.

    Science.gov (United States)

    The antimicrobial activity activity of extracts of the hop plant Humulus lupus was studied in chickens fed diets without antibiotic growth promotants. Beta-acid resins of the hop plant were administered by water to 13 day old chickens subsequently challenged per so with necrotic enteritis-associate...

  3. Immune responses and protection against experimental challenge after vaccination of bison with Brucella abortus strains RB51 or RB51 overexpressing superoxide dismutase and Glycosyltransferase genes

    Science.gov (United States)

    Vaccination is a tool that could be beneficial in managing the high prevalence of brucellosis in free-ranging bison in Yellowstone National Park. In this study, we characterized immunologic responses and protection against experimental challenge after vaccination of bison with Brucella abortus stra...

  4. Immune responses to modified live virus vaccines developed from classical or highly pathogenic PRRSV following challenge with a highly pathogenic PRRSV strain.

    Science.gov (United States)

    Wang, Gang; Yu, Ying; Zhang, Chong; Tu, Yabin; Tong, Jie; Liu, Yonggang; Chang, Yafei; Jiang, Chenggang; Wang, Shujie; Zhou, En-Min; Cai, Xuehui

    2016-09-01

    Modified live virus vaccines (MLVs) are used on swine farms to control porcine reproductive and respiratory syndrome virus (PRRSV). MLVs from classical PRRSV (C-PRRSV) provide some protection against emergent highly pathogenic PRRSV (HP-PRRSV). This study characterized the protective efficacy and immune response to MLVs from C-PRRSV (CH-1R) or HP-PRRSV (HuN4-F112) in a challenge using HP-PRRSV (HuN4). The outcomes were clinical signs of disease, pathological changes in the thymus and lungs, viremia, and humoral and cellular immune responses. CH-1R provided some protection against challenge with HuN4, while HuN4-F112 was protective in the HuN4 challenge. Compared to unvaccinated piglets, the vaccinated piglets had milder symptoms and fewer pathological changes in the lung and thymus. Piglets vaccinated with HuN4-F112 had higher antibody titers and lower viral loads than piglets vaccinated with CH-1R post challenge. The differences in outcome between the MLVs suggested that underlying differences in the immune responses might warrant further study. PMID:27119981

  5. Exploiting the inter-strain divergence of Fusarium oxysporum for microbial bioprocessing of lignocellulose to bioethanol

    OpenAIRE

    Ali, Shahin S; Khan, Mojibur; Fagan, Brian; Mullins, Ewen; Fiona M Doohan

    2012-01-01

    Microbial bioprocessing of lignocellulose to bioethanol still poses challenges in terms of substrate catabolism. A targeted evolution-based study was undertaken to determine if inter-strain microbial variability could be exploited for bioprocessing of lignocellulose to bioethanol. The microorganism studied was Fusarium oxysporum because of its capacity to both saccharify and ferment lignocellulose. Strains of F. oxysporum were isolated and assessed for their genetic variability. Using optimis...

  6. Outcome of EPIZONE Extension ON VER/VNN: Pathogenicity study of 10 betanodavirus strains with an in vivo challenge in European sea bass (Dicentrarchus labrax)

    DEFF Research Database (Denmark)

    Vendramin, Niccolò; Toffan, A.; Cappellozza, E.;

    2012-01-01

    detected in wild fish as well as other aquatic organisms (artemia, rotifers, molluscs and crustaceans) in addition to farmed fish. The RGNNV genotype is the most widespread in the Mediterranean region, nevertheless some strains, characterized by containing genetic material belonging to both the RGNNV and......Viral encephalopathy and retinopathy (VER) otherwise known as viral nervous necrosis (VNN) is a severe pathological condition, caused by small RNA viruses belonging to the Nodaviridae family, genus Betanodavirus. The disease, which has been described in more than 45 fish species worldwide, is...... considered the most serious viral threat affecting marine farmed species in the Mediterranean region, thus representing one of the bottlenecks for further development of aquaculture industry. Epidemiological investigations carried out in different geographical areas demonstrated that Betanodavirus can be...

  7. Design of homo-organic acid producing strains using multi-objective optimization

    DEFF Research Database (Denmark)

    Kim, Tae Yong; Park, Jong Myoung; Kim, Hyun Uk;

    2015-01-01

    Production of homo-organic acids without byproducts is an important challenge in bioprocess engineering to minimize operation cost for separation processes. In this study, we used multi-objective optimization to design Escherichia coli strains with the goals of maximally producing target organic ...

  8. Oral re-vaccination of Eurasian wild boar with Mycobacterium bovis BCG yields a strong protective response against challenge with a field strain

    OpenAIRE

    Gortázar, Christian; Beltrán-Beck, Beatriz; Joseba M. Garrido; Aranaz, Alicia; Sevilla, Iker A.; Boadella, Mariana; Lyashchenko, Konstantin P; Galindo, Ruth C.; Montoro, Vidal; Domínguez, Lucas; Juste, Ramón; De La Fuente, Jose

    2014-01-01

    Abstract Background Field vaccination trials with Mycobacterium bovis BCG, an attenuated mutant of M. bovis, are ongoing in Spain, where the Eurasian wild boar (Sus scrofa) is regarded as the main driver of animal tuberculosis (TB). The oral baiting strategy consists in deploying vaccine baits twice each summer, in order to gain access to a high proportion of wild boar piglets. The aim of this study was to assess the response of wild boar to re-vaccination with BCG and to subsequent challenge...

  9. RecET driven chromosomal gene targeting to generate a RecA deficient Escherichia coli strain for Cre mediated production of minicircle DNA

    Directory of Open Access Journals (Sweden)

    Coutelle Charles

    2006-03-01

    Full Text Available Abstract Background Minicircle DNA is the non-replicating product of intramolecular site-specific recombination within a bacterial minicircle producer plasmid. Minicircle DNA can be engineered to contain predominantly human sequences which have a low content of CpG dinucleotides and thus reduced immunotoxicity for humans, whilst the immunogenic bacterial origin and antibiotic resistance marker gene sequences are entirely removed by site-specific recombination. This property makes minicircle DNA an excellent vector for non-viral gene therapy. Large-scale production of minicircle DNA requires a bacterial strain expressing tightly controlled site-specific recombinase, such as Cre recombinase. As recombinant plasmids tend to be more stable in RecA-deficient strains, we aimed to construct a recA- bacterial strain for generation of minicircle vector DNA with less chance of unwanted deletions. Results We describe here the construction of the RecA-deficient minicircle DNA producer Escherichia coli HB101Cre with a chromosomally located Cre recombinase gene under the tight control of the araC regulon. The Cre gene expression cassette was inserted into the chromosomal lacZ gene by creating transient homologous recombination proficiency in the recA- strain HB101 using plasmid-born recET genes and homology-mediated chromosomal "pop-in, pop-out" of the plasmid pBAD75Cre containing the Cre gene and a temperature sensitive replication origin. Favourably for the Cre gene placement, at the "pop-out" step, the observed frequency of RecET-led recombination between the proximal regions of homology was 10 times higher than between the distal regions. Using the minicircle producing plasmid pFIXluc containing mutant loxP66 and loxP71 sites, we isolated pure minicircle DNA from the obtained recA- producer strain HB101Cre. The minicircle DNA preparation consisted of monomeric and, unexpectedly, also multimeric minicircle DNA forms, all containing the hybrid loxP66

  10. Current Challenges in Detecting Food Allergens by Shotgun and Targeted Proteomic Approaches: A Case Study on Traces of Peanut Allergens in Baked Cookies

    OpenAIRE

    Romina Pedreschi; Jørgen Nørgaard; Alain Maquet

    2012-01-01

    There is a need for selective and sensitive methods to detect the presence of food allergens at trace levels in highly processed food products. In this work, a combination of non-targeted and targeted proteomics approaches are used to illustrate the difficulties encountered in the detection of the major peanut allergens Ara h 1, Ara h 2 and Ara h 3 from a representative processed food matrix. Shotgun proteomics was employed for selection of the proteotypic peptides for targeted approaches via...

  11. Use of Hypocrea jecorina (anamorph Trichoderma reesei) as a model system for Trichoderma biocontrol of Pythium blight identifies new targets for genetic strain improvement

    Institute of Scientific and Technical Information of China (English)

    Seidl V; Schmoll M; Scherm B; Balmas V; Seiboth B; Migheli Q; Kubicek C P

    2004-01-01

    @@ Biocontrol by Trichoderma has been studied mainly with selected isolates of T. harzianum, T.atroviride and T. asperellum, which are members of sections Pachybasium and Trichoderma. In contrast, species from section Longibrachiatum have only rarely been studied. On the other hand, one taxon from this section-Hypocrea jecorina (anamorph: Trichoderma reesei)-has been widely used for the production of cellulolytic and hemicellulolytic enzymes and recombinant proteins. As far as Trichoderma is concerned, molecular genetic methods and tools are most advanced in H. jecorina,and its genome has recently been fully sequenced, thus making this taxon a model organism for the genus. Here we will demonstrate that H. jecorina is able to antagonize plant pathogenic fungi in plate confrontation tests, and can protect tomato and cucumber plants against Pythium ultimum blight.Using this as a model case, we made use of available H. jecorina mutants to investigate (a) whether carbon catabolite repression via the Cre1-regulator protein has an impact on biocontrol, and (b)whether cellulase gene expression is necessary for biocontrol of P. ultimum. In the first case, plate confrontation tests and in planta experiments yielded opposite results, i.e. while a Cre1 mutant was more active in antagonization of fungi on plates, the survival rates of P. ultimum-inoculated cucumber plants was lower than with the H. jecorina wild-type strain. Mutants of H. jecorina,unable to form cellulases, were still able to antagonize fungi on plates and provided similar protection of tomatos against P. ultimum as the wild type, indicating that the pronounced biocontrol ability of H.jecorina against fungi with cellulose-containing cell-walls is not due to its high cellulolytic activity. A strain disrupted in the light-modulator gene envoy (Schmoll et al., ms submitted) exhibited in planta biocontrol activity strongly exceeding that of the wild-type strain, thereby providing a first link between Trichoderma

  12. Challenging the state-of-the-art in protein structure prediction: Highlights of experimental target structures for the 10th Critical Assessment of Techniques for Protein Structure Prediction Experiment CASP10

    Science.gov (United States)

    Kryshtafovych, Andriy; Moult, John; Bales, Patrick; Bazan, J. Fernando; Biasini, Marco; Burgin, Alex; Chen, Chen; Cochran, Frank V.; Craig, Timothy K.; Das, Rhiju; Fass, Deborah; Garcia-Doval, Carmela; Herzberg, Osnat; Lorimer, Donald; Luecke, Hartmut; Ma, Xiaolei; Nelson, Daniel C.; van Raaij, Mark J.; Rohwer, Forest; Segall, Anca; Seguritan, Victor; Zeth, Kornelius; Schwede, Torsten

    2014-01-01

    For the last two decades, CASP has assessed the state of the art in techniques for protein structure prediction and identified areas which required further development. CASP would not have been possible without the prediction targets provided by the experimental structural biology community. In the latest experiment, CASP10, over 100 structures were suggested as prediction targets, some of which appeared to be extraordinarily difficult for modeling. In this paper, authors of some of the most challenging targets discuss which specific scientific question motivated the experimental structure determination of the target protein, which structural features were especially interesting from a structural or functional perspective, and to what extent these features were correctly reproduced in the predictions submitted to CASP10. Specifically, the following targets will be presented: the acid-gated urea channel, a difficult to predict trans-membrane protein from the important human pathogen Helicobacter pylori; the structure of human interleukin IL-34, a recently discovered helical cytokine; the structure of a functionally uncharacterized enzyme OrfY from Thermoproteus tenax formed by a gene duplication and a novel fold; an ORFan domain of mimivirus sulfhydryl oxidase R596; the fibre protein gp17 from bacteriophage T7; the Bacteriophage CBA-120 tailspike protein; a virus coat protein from metagenomic samples of the marine environment; and finally an unprecedented class of structure prediction targets based on engineered disulfide-rich small proteins. PMID:24318984

  13. Novel Clostridium difficile Anti-Toxin (TcdA and TcdB) Humanized Monoclonal Antibodies Demonstrate In Vitro Neutralization across a Broad Spectrum of Clinical Strains and In Vivo Potency in a Hamster Spore Challenge Model

    Science.gov (United States)

    Qiu, Hongyu; Cassan, Robyn; Johnstone, Darrell; Han, Xiaobing; Joyee, Antony George; McQuoid, Monica; Masi, Andrea; Merluza, John; Hrehorak, Bryce; Reid, Ross; Kennedy, Kieron; Tighe, Bonnie; Rak, Carla; Leonhardt, Melanie; Dupas, Brian; Saward, Laura; Berry, Jody D.; Nykiforuk, Cory L.

    2016-01-01

    Clostridium difficile (C. difficile) infection (CDI) is the main cause of nosocomial antibiotic-associated colitis and increased incidence of community-associated diarrhea in industrialized countries. At present, the primary treatment of CDI is antibiotic administration, which is effective but often associated with recurrence, especially in the elderly. Pathogenic strains produce enterotoxin, toxin A (TcdA), and cytotoxin, toxin B (TcdB), which are necessary for C. difficile induced diarrhea and gut pathological changes. Administration of anti-toxin antibodies provides an alternative approach to treat CDI, and has shown promising results in preclinical and clinical studies. In the current study, several humanized anti-TcdA and anti-TcdB monoclonal antibodies were generated and their protective potency was characterized in a hamster infection model. The humanized anti-TcdA (CANmAbA4) and anti-TcdB (CANmAbB4 and CANmAbB1) antibodies showed broad spectrum in vitro neutralization of toxins from clinical strains and neutralization in a mouse toxin challenge model. Moreover, co-administration of humanized antibodies (CANmAbA4 and CANmAbB4 cocktail) provided a high level of protection in a dose dependent manner (85% versus 57% survival at day 22 for 50 mg/kg and 20 mg/kg doses, respectively) in a hamster gastrointestinal infection (GI) model. This study describes the protective effects conferred by novel neutralizing anti-toxin monoclonal antibodies against C. difficile toxins and their potential as therapeutic agents in treating CDI. PMID:27336843

  14. Challenge of conducting a placebo-controlled randomized efficacy study for influenza vaccine in a season with low attack rate and a mismatched vaccine B strain: a concrete example

    Directory of Open Access Journals (Sweden)

    Jirincova Helena

    2009-01-01

    Full Text Available Abstract Background Our aim was to determine the efficacy of a trivalent inactivated split virus influenza vaccine (TIV against culture-confirmed influenza A and/or B in adults 18 to 64 years of age during the 2005/2006 season in the Czech Republic. Methods 6203 subjects were randomized to receive TIV (N = 4137 or placebo (N = 2066. The sample size was based on an assumed attack rate of 4% which provided 90% power to reject the hypothesis that vaccine efficacy (VE was ≥ 45%. Cases of influenza like illness (defined as fever (oral temperature ≥37.8°C plus cough and/or sore throat were identified both by active (biweekly phone contact and passive (self reporting surveillance and nasal and throat swabs were collected from subjects for viral culture. Results TIV was well tolerated and induced a good immune response. The 2005/2006 influenza season was exceptionally mild in the study area, as it was throughout Europe, and only 46 culture-confirmed cases were found in the study cohort (10 influenza A and 36 influenza B. Furthermore among the B isolates, 35 were identified as B/Hong Kong 330/2001-like (B/Victoria/2/87 lineage which is antigenically unrelated to the vaccine B strain (B/Yamagata/16/88 lineage. The attack rate in the vaccine group (0.7% was not statistically significantly different from the attack rate in the placebo group (0.9%. Conclusion Due to the atypical nature of the influenza season during this study we were unable to assess TIV efficacy. This experience illustrates the challenge of conducting a prospective influenza vaccine efficacy trial during a single season when influenza attack rates and drift in circulating strains or B virus lineage match can be difficult to estimate in advance. Trial Registration Clinical trial registery: NCT00197223.

  15. Novel Clostridium difficile Anti-Toxin (TcdA and TcdB Humanized Monoclonal Antibodies Demonstrate In Vitro Neutralization across a Broad Spectrum of Clinical Strains and In Vivo Potency in a Hamster Spore Challenge Model.

    Directory of Open Access Journals (Sweden)

    Hongyu Qiu

    Full Text Available Clostridium difficile (C. difficile infection (CDI is the main cause of nosocomial antibiotic-associated colitis and increased incidence of community-associated diarrhea in industrialized countries. At present, the primary treatment of CDI is antibiotic administration, which is effective but often associated with recurrence, especially in the elderly. Pathogenic strains produce enterotoxin, toxin A (TcdA, and cytotoxin, toxin B (TcdB, which are necessary for C. difficile induced diarrhea and gut pathological changes. Administration of anti-toxin antibodies provides an alternative approach to treat CDI, and has shown promising results in preclinical and clinical studies. In the current study, several humanized anti-TcdA and anti-TcdB monoclonal antibodies were generated and their protective potency was characterized in a hamster infection model. The humanized anti-TcdA (CANmAbA4 and anti-TcdB (CANmAbB4 and CANmAbB1 antibodies showed broad spectrum in vitro neutralization of toxins from clinical strains and neutralization in a mouse toxin challenge model. Moreover, co-administration of humanized antibodies (CANmAbA4 and CANmAbB4 cocktail provided a high level of protection in a dose dependent manner (85% versus 57% survival at day 22 for 50 mg/kg and 20 mg/kg doses, respectively in a hamster gastrointestinal infection (GI model. This study describes the protective effects conferred by novel neutralizing anti-toxin monoclonal antibodies against C. difficile toxins and their potential as therapeutic agents in treating CDI.

  16. Success and Challenges of a Community Healthy Lifestyles Intervention in Merseyside (UK) to Target Families at Risk from Coronary Heart Disease

    Science.gov (United States)

    Peerbhoy, D.; Majumdar, A. J.; Wightman, N. A.; Brand, V. L.

    2008-01-01

    Objective: To document the lifestyle health impacts (activity, diet and physiological), along with the operational success and challenges, of a programme for families presenting one or more coronary heart disease (CHD) risk factor. Design: Data are based on a wider evaluation of a government-funded community initiative conducted in a deprived area…

  17. A novel recombinant Mycobacterium bovis bacillus Calmette-Guerin strain expressing human granulocyte macrophage colony-stimulating factor and Mycobacterium tuberculosis early secretory antigenic target 6 complex augments Th1 immunity

    Institute of Scientific and Technical Information of China (English)

    Xiaoling Yang; Lang Bao; Yihao Deng

    2011-01-01

    Since Mycobacterium bovis bacillus Calmette-Guerin strain (BCG) fails to protect adults from pulmonary tuberculosis (TB), there is an urgent need for developing a new vaccine. In this study, we constructed a novel recombinant BCG strain (rBCG) expressing human granulocyte macrophage colony-stimulating factor (GM-CSF) and the 6 kDa early secretory antigenic target (ESAT6) of Mycobacteriutn tuberculosis, named rBCG:GE (expressing GMCSFESAT6 complex), and evaluated the immunogenicity of the construct in BALB/c mice. Our results indicated that the rBCG:GE was able to induce higher titer of antibody than the conventional BCG, the rBCG:G (expressing GM-CSF)and the rBCG:E (expressing ESAT6). Moreover, the rBCG:GE also elicited a longer-lasting and stronger Thl cellular immune responses than the other groups, which was confirmed by the incremental proliferation of splenocytes, the increased percentages of CD4+ and CD8+ T cells of spleen, the elevated level of interferon-γ in splenocyte culture after tuberculin-purified protein derivative stimulation, and the increased concentration of GM-CSF in serum. The data presented here suggested the possibility that the recombinant BCG:GE might be a good vaccine candidate to TB.

  18. Novel HIV-1 Therapeutics through Targeting Altered Host Cell Pathways

    OpenAIRE

    Coley, William; Kehn-Hall, Kylene; Van Duyne, Rachel; KASHANCHI, FATAH

    2009-01-01

    The emergence of drug-resistant human immunodeficiency virus type I (HIV-1) strains presents a challenge for the design of new drugs. Anti-HIV compounds currently in use are the subject of advanced clinical trials using either HIV-1 reverse-transcriptase, viral protease, or integrase inhibitors. Recent studies show an increase in the number of HIV-1 variants resistant to anti-retroviral agents in newly infected individuals. Targeting host cell factors involved in the regulation of HIV-1 repli...

  19. Targeted Capture Sequencing in Whitebark Pine Reveals Range-Wide Demographic and Adaptive Patterns Despite Challenges of a Large, Repetitive Genome

    Science.gov (United States)

    Syring, John V.; Tennessen, Jacob A.; Jennings, Tara N.; Wegrzyn, Jill; Scelfo-Dalbey, Camille; Cronn, Richard

    2016-01-01

    Whitebark pine (Pinus albicaulis) inhabits an expansive range in western North America, and it is a keystone species of subalpine environments. Whitebark is susceptible to multiple threats – climate change, white pine blister rust, mountain pine beetle, and fire exclusion – and it is suffering significant mortality range-wide, prompting the tree to be listed as ‘globally endangered’ by the International Union for Conservation of Nature and ‘endangered’ by the Canadian government. Conservation collections (in situ and ex situ) are being initiated to preserve the genetic legacy of the species. Reliable, transferrable, and highly variable genetic markers are essential for quantifying the genetic profiles of seed collections relative to natural stands, and ensuring the completeness of conservation collections. We evaluated the use of hybridization-based target capture to enrich specific genomic regions from the 27 GB genome of whitebark pine, and to evaluate genetic variation across loci, trees, and geography. Probes were designed to capture 7,849 distinct genes, and screening was performed on 48 trees. Despite the inclusion of repetitive elements in the probe pool, the resulting dataset provided information on 4,452 genes and 32% of targeted positions (528,873 bp), and we were able to identify 12,390 segregating sites from 47 trees. Variations reveal strong geographic trends in heterozygosity and allelic richness, with trees from the southern Cascade and Sierra Range showing the greatest distinctiveness and differentiation. Our results show that even under non-optimal conditions (low enrichment efficiency; inclusion of repetitive elements in baits), targeted enrichment produces high quality, codominant genotypes from large genomes. The resulting data can be readily integrated into management and gene conservation activities for whitebark pine, and have the potential to be applied to other members of 5-needle pine group (Pinus subsect. Quinquefolia) due to

  20. Targeted capture sequencing in whitebark pine reveals range-wide demographic and adaptive patterns despite challenges of a large, repetitive genome

    Directory of Open Access Journals (Sweden)

    John eSyring

    2016-04-01

    Full Text Available Whitebark pine (Pinus albicaulis inhabits an expansive range in western North America, and it is a keystone species of subalpine environments. Whitebark is susceptible to multiple threats – climate change, white pine blister rust, mountain pine beetle, and fire exclusion – and it is suffering significant mortality range-wide, prompting the tree to be listed as ‘globally endangered’ by the International Union for Conservation of Nature (IUCN and ‘endangered’ by the Canadian government. Conservation collections (in situ and ex situ are being initiated to preserve the genetic legacy of the species. Reliable, transferrable, and highly variable genetic markers are essential for quantifying the genetic profiles of seed collections relative to natural stands, and ensuring the completeness of conservation collections. We evaluated the use of hybridization-based target capture to enrich specific genomic regions from the 30+ GB genome of whitebark pine, and to evaluate genetic variation across loci, trees, and geography. Probes were designed to capture 7,849 distinct genes, and screening was performed on 48 trees. Despite the inclusion of repetitive elements in the probe pool, the resulting dataset provided information on 4,452 genes and 32% of targeted positions (528,873 bp, and we were able to identify 12,390 segregating sites from 47 trees. Variations reveal strong geographic trends in heterozygosity and allelic richness, with trees from the southern Cascade and Sierra Range showing the greatest distinctiveness and differentiation. Our results show that even under non-optimal conditions (low enrichment efficiency; inclusion of repetitive elements in baits, targeted enrichment produces high quality, codominant genotypes from large genomes. The resulting data can be readily integrated into management and gene conservation activities for whitebark pine, and have the potential to be applied to other members of 5-needle pine group (Pinus subsect

  1. Avaliação hematológica pós-desafio com cepa virulenta de Eimeria tenella em frangos de corte imunizados com cepa atenuada ou proteínas de esporozoítos de cepa homóloga Post-challenge hematological evaluation with virulent strain of Eimeria tenella in broilers immunized with attenuated strain or sporozoite proteins from homologous strain

    Directory of Open Access Journals (Sweden)

    Alexey Leon Gomel Bogado

    2010-03-01

    Full Text Available Foram avaliados os parâmetros hematológicos em frangos de corte imunizados e desafiados com Eimeria tenella. Pintos de corte fêmeas da linhagem Hubbard, livres de coccídios, foram mantidos em baterias metálicas e inoculados no terceiro dia. O experimento foi delineado por cinco tratamentos com três repetições cada, sendo: T1 controle negativo, T2 recebeu 500 oocistos esporulados atenuados via oral, T3 controle positivo, T4 recebeu vacina contendo 50 µg de proteínas de esporozoítos + Quil A e T5 recebeu Quil A + PBS, sendo os dois últimos por via nasal nos dias 0, 7 e 21. No dia 31, todos os tratamentos foram desafiados com cepa virulenta homóloga de E. tenella na dose de 8,0 × 10(4 oocistos, exceto T1. Uma semana depois, foi realizada amostragem de sangue, escore de lesão e contagem de oocistos cecais. Os parâmetros parasitológicos apresentaram significância estatística (p 0,05, pelo teste ANOVA. As correlações sugerem que os parâmetros sanguíneos foram afetados pelos efeitos do parasita no tecido, apresentando níveis de hemorragia e/ou hidratação.Hematological parameters were evaluated in broilers immunized and challenged with Eimeria tenella. Broiler chickens of Hubbard strain, females, coccidian-free, were kept in wire cages and inoculated on the third day. The experiment was designed to include five sorts of treatment with three replicates each. T1 was the negative control group, T2 received 500 attenuated sporulated oocysts by gavage, T3 was the positive control, T4 received 50 µg of sporozoite protein + Quil A vaccine, and T5 received Quil A without sporozoite protein + PBS, the last two through nasal route on days 0, 7, and 21. On the 31st day, all treatments were challenged with homologous virulent strain of E. tenella in the dose of 8.0 × 10(4 oocysts, with the exception of T1. One week later, blood sampling, lesion scores, and cecal oocyst count were carried out. The parasitological parameters showed

  2. Reconstruction of axisymmetric strain distributions via neutron strain tomography

    International Nuclear Information System (INIS)

    Predicting the behaviour of structural components under a particular set of loading conditions requires knowledge of the residual elastic strain distribution throughout the bulk of these components. Characterising the 3D strain state at any particular point involves the measurement of six independent components which make up the second order strain tensor. Mapping the complete strain distribution throughout large volumes thus presents significant practical challenges. One possible solution to this problem is to reconstruct the 3D variation of strain components using tomographic techniques. The basic principle underpinning this idea is that the multi-component strain tensor can be reconstructed from a redundant set of lower order projection data. Here we demonstrate this fundamental concept for two samples: a shrink fit ‘ring-and-plug’ sample, and a spray-quenched circular cylinder, both possessing axially symmetric internal strain distribution. We present and contrast different approaches to the strain tomography problem. The methods described here can also be readily applied to high-energy X-ray diffraction measurements and represent an important step toward developing the tomographic reconstruction framework for strain tensor distributions of arbitrary complexity. The major benefit of neutron strain tomography is that the incident beam flux is utilised more fully, greatly reducing the data collection times. Using micro-channel plate (MCP) neutron detectors, a spatial resolution of the order of 0.1 mm can be achieved .

  3. The Role of Precision Medicine in Pancreatic Cancer: Challenges for Targeted Therapy, Immune Modulating Treatment, Early Detection, and Less Invasive Operations

    Directory of Open Access Journals (Sweden)

    Khaled Kyle Wong

    2016-01-01

    Full Text Available Pancreatic cancer is one of the most lethal types of cancer due to its heterogeneous nature and the difficulty of detecting lesions in the pancreas during the early stages of tumorigenesis. Until recently, progress has been slow in developing methods to detect pancreatic lesions early. However, recent advances in genetics, biomarkers, imaging, and surgical procedures have aided the early detection of such lesions before the incurable metastatic disease state. Precision medicine has benefited pancreatic cancer patients in such areas as genetics, more targeted approaches to therapy, immunotherapy advances, and the discovery of more ideal biomarkers. In this review, the various studies and trials in these areas were reviewed to illustrate the promise of precision medicine.

  4. Target Window Reliability

    Energy Technology Data Exchange (ETDEWEB)

    Woloshun, Keith Albert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-02-11

    The target window design implemented and tested in experiments at ANL have performed without failure for the available beam of 6 mm FWHM on a 12 mm diameter target. However, scaling that design to a 25 mm diameter target size for a 12 mm FWHM beam has proven problematic. Combined thermal and mechanical (pressure induced) stresses and strains are too high to maintain the small coolant gaps and provide adequate fatigue lifetime.

  5. Targeted cancer therapies

    Institute of Scientific and Technical Information of China (English)

    Li Yan; Neal Rosen; Carlos Arteaga

    2011-01-01

    With unprecedented understanding of molecular events underlying human cancer in this genomic era, a large number of drugs specifically targeting hypothesized oncogenic drivers to which tumors are potentially addicted to have been developed and continue to be developed. These targeted cancer therapies are being actively tested in clinical trials with mixed successes. This editorial provides an overview on successful targeted cancer drugs on the market and those drugs that are in late clinical development stages. Importantly, the article lays out main challenges in developing molecular targeted therapies and potential path forward to overcome these challenges, as well as opportunities for China in this new era of targeted agents. The editorial serves as an introduction to the Targeted Cancer Therapies serias that will review in depth of major pathways and drugs targeting these pathways to be published in the coming issues of the Chinese Journal of Cancer.

  6. Pin clad strains in Phenix

    International Nuclear Information System (INIS)

    The Phenix reactor has operated for 4 years in a satisfactory manner. The first 2 sub-assembly loadings contained pins clad in solution treated 316. The principal pin strains are: diametral strain (swelling and irradiation creep), ovality and spiral bending of the pin (interaction of wire and pin cluster and wrapper). A pin cluster irradiated to a dose of 80 dpa F reached a pin diameter strain of 5%. This strain is principally due to swelling (low fission gas pressure). The principal parameters governing the swelling are instantaneous dose, time and temperature for a given type of pin cladding. Other types of steel are or will be irradiated in Phenix. In particular, cold-worked titanium stabilised 316 steel should contribute towards a reduction in the pin clad strains and increase the target burn-up in this reactor. (author)

  7. Challenges in Danish VET

    DEFF Research Database (Denmark)

    Aarkrog, Vibe

    2011-01-01

    In Denmark the 95 percent target, meaning that in 2015 95 percent of a youth cohort should complete a youth education programme, is particularly challenging for the vocational educational and training (VET) system. In the article is given a short outline of the significant characteristics of the...... Danish dual VET system as well as of the current central initiatives aimed at reaching the 95 percent target....

  8. Moving Target Defense

    CERN Document Server

    Jajodia, Sushil; Swarup, Vipin; Wang, Cliff; Wang, X Sean

    2011-01-01

    Moving Target Defense: Creating Asymmetric Uncertainty for Cyber Threats was developed by a group of leading researchers. It describes the fundamental challenges facing the research community and identifies new promising solution paths. Moving Target Defense which is motivated by the asymmetric costs borne by cyber defenders takes an advantage afforded to attackers and reverses it to advantage defenders. Moving Target Defense is enabled by technical trends in recent years, including virtualization and workload migration on commodity systems, widespread and redundant network connectivity, instr

  9. 重组肝靶向干扰素工程菌菌株的遗传稳定性研究%Genetic stability of recombinant liver-targeting interferon engineered bacteria strains

    Institute of Scientific and Technical Information of China (English)

    卢雪梅; 黄演婷; 汪洁; 金小宝; 朱家勇

    2013-01-01

    This study aimed to investigate the genetic stability of recombinant plasmid (pET32α-IFN-CSP) in host cell (Escherichia coli BL21) for industrialization of recombinant liver-targeting interferon.The engineering strain containing pET32α-IFN-CSP expression vectors was passaged serially under selection pressure (AMP) on LB agar plates for 50 times,and bacterial morphology,growth rate,plasmid stability,PCR identification,restriction enzyme map,sequencing and expressing level were analyzed.The experiment showed that the engineered bacteria maintained the typical characteristics of E.coli in a continuous passage process,no significant difference in the growth rate as the original seed bank ; PCR and restriction map of the plasmid were correct,the plasmid stability was nearly 100% and DNA sequencing was no genetic variation after passed through 50 generations.The expression levels of recombinant liver-targeting interferon and the map of SDS-PAGE of cell protein were similar with the origin one.There was no significant difference between the recombinant bacteria of the 50 generations and the original ones,which indicated that recombinant stainhad a high hereditable stability and laid a basis for the application of recombinant liver-targeting interferon.%研究重组肝靶向干扰素工程菌菌株的遗传稳定性,为重组肝靶向干扰素产业化提供依据.在有选择压力(Amp+)条件下,采用平板划线传代法,将重组肝靶向干扰素工程菌菌株连续传代50代,观察菌落和菌体形态,进行生长速度、质粒稳定性、PCR鉴定、限制性内切酶酶切图谱、测序和表达量检测.结果显示:此工程菌在连续传代过程中,保持了大肠杆菌的典型特征,生长速度与原始种子库无明显差异;各代质粒的PCR和酶切图谱正确,传50代后质粒稳定性接近100%,DNA测序未见基因变异.重组肝靶向干扰素表达水平及菌体蛋白的SDS-PAGE图谱均无显著差异.说明肝靶向干扰素

  10. Energy challenges

    International Nuclear Information System (INIS)

    Satisfying the world's insatiable appetite for fuel without destroying the environment is the biggest challenge facing the energy industry. World energy consumption is expected to soar by 50% to a staggering 180 000 GW h per year by 2020, with the developing world demanding an ever-increasing share. Although oil and natural-gas reserves will last for several more decades, environmental concerns are increasingly dominating the agenda. Last year 178 countries agreed to a watered-down version of the original Kyoto protocol, which was designed to reduce the emissions of greenhouse gases from industrialized countries by an average of 5.2% below 1990 levels. Under the new agreement, dubbed 'Kyoto lite' by environmentalists, emissions will be cut by just 2%. The relaxed targets are still not enough to convince the US, the world's biggest polluter, to sign the Kyoto treaty. Renewable technologies still make up less than 1% of the world's commercial energy. Distributed power is also likely to emerge from the development of fuel cells - devices that convert the chemical energy of hydrogen and oxygen directly into electricity, with only water as a by-product. The move away from carbon-based fossil fuels to hydrogen is also driving the hydrogen economy. A longer-term possibility is nuclear fusion. Despite the enormous progress in the performance of experiments over the past 30 years, nuclear fusion is still decades away from generating electricity. Advocates of fusion power claim that it could be a safe and sustainable source of energy that does not produce any greenhouse gases or long-lived nuclear waste. However, physicists have still to demonstrate that the energy produced by the fusion of deuterium and tritium can be sustained. Advances in physics and engineering are making energy from renewable sources increasingly affordable. But political will - as well as scientific progress - is just as crucial for safeguarding the environment for generations to come

  11. Predicting nutrient responses in poultry: future challenges.

    Science.gov (United States)

    Gous, R M

    2007-02-01

    Predicting the response of poultry to nutrients has progressed to a stage where it is now not only possible to predict voluntary feed intake accurately, but broiler feeds and feeding programmes may now be optimised using the more advanced simulation models. Development of such prediction models has stimulated useful and purposeful research targeted at filling the gaps in our knowledge of critical aspects of the theory incorporated into these models. The aim of this paper was to review some of these past developments, discuss the controversy that exists in designing and interpreting response experiments, and highlight some of the most recent challenges related to the prediction of responses to nutrients by poultry. These latter include differences, brought about by selection for diverse goals, that have become apparent between modern broiler strains in their responses in feed intake and mortality, which are not independent of level of feeding or strain of broiler, as was previously believed. Uniformity, an important quality criterion in broiler processing, is also not independent of level of feeding, and the effect may now be predicted using stochastic models. It is not yet clear whether breast meat yield, the carcass component of broilers yielding the highest returns, is a function of the strain of broiler or simply that of the protein weight of the bird when processed. An important aspect of response prediction is dealing with constraints to performance: whereas it is relatively straightforward to simulate the potential performance of a broiler, such performance is often constrained by the physical, social and infectious environment, among others, providing a challenge to modellers attempting to predict actual performance. Some of these constraints to potential performance have not yet been adequately described, but are now receiving attention, suggesting that nutrient responses in poultry have the potential to be more accurately predicted in the future. PMID

  12. Effect of dietary addition of nitrate on growth, salivary and gastric function, immune response, and excretion of Salmonella enterica serovar Typhimurium, in weaning pigs challenged with this microbe strain

    Directory of Open Access Journals (Sweden)

    M. Mazzoni

    2010-04-01

    Full Text Available Two dietary additions of nitrate (15 mg/kg or 150 mg/kg, supplied by potassium salt were tested in a total 96 weaning pigs challenged or not with Salmonella enterica serovar typhimurium (ST. The oral challenge was done on d 5 and pigs were sacrificed on d 7 or d 25. The effect of challenge never interacted significantly with the dietary treatment. Feed intake, growth, body temperature, salivary excretion, and faecal excretion of ST and gastric function were not affected by the nitrate supplementation. With nitrate additions, total IgA in blood serum tended to be higher before and after the challenge (P<0.10. Nitrite in saliva – but not nitrate – increased with the increasing supplementation at d 5, but not at d 19. The nitrate additions did not negatively affect the weaning performance, but also did not contrast the effect of ST infection.

  13. Extracting full-field dynamic strain response of a rotating wind turbine using photogrammetry

    Science.gov (United States)

    Baqersad, Javad; Poozesh, Peyman; Niezrecki, Christopher; Avitabile, Peter

    2015-04-01

    Health monitoring of wind turbines is typically performed using conventional sensors (e.g. strain-gages and accelerometers) that are usually mounted to the nacelle or gearbox. Although many wind turbines stop operating due to blade failures, there are typically few to no sensor mounted on the blades. Placing sensors on the rotating parts of the structure is a challenge due to the wiring and data transmission constraints. Within the current work, an approach to monitor full-field dynamic response of rotating structures (e.g. wind turbine blades or helicopter rotors) is developed and experimentally verified. A wind turbine rotor was used as the test structure and was mounted to a block and horizontally placed on the ground. A pair of bearings connected to the rotor shaft allowed the turbine to freely spin along the shaft. Several optical targets were mounted to the blades and a pair of high-speed cameras was used to monitor the dynamics of the spinning turbine. Displacements of the targets during rotation were measured using three-dimensional point tracking. The point tracking technique measured both rigid body displacement and flexible deformation of the blades at target locations. While the structure is rotating, only flap displacements of optical targets (displacements out of the rotation plane) were used in strain prediction process. The measured displacements were expanded and applied to the finite element model of the turbine to extract full-field dynamic strain on the structure. The proposed approach enabled the prediction of dynamic response on the outer surface as well as within the inner points of the structure where no other sensor could be easily mounted. In order to validate the proposed approach, the predicted strain was compared to strain measured at four locations on the spinning blades using a wireless strain-gage system.

  14. Antiviral targets of human noroviruses.

    Science.gov (United States)

    Prasad, Bv Venkataram; Shanker, Sreejesh; Muhaxhiri, Zana; Deng, Lisheng; Choi, Jae-Mun; Estes, Mary K; Song, Yongcheng; Palzkill, Timothy; Atmar, Robert L

    2016-06-01

    Human noroviruses are major causative agents of sporadic and epidemic gastroenteritis both in children and adults. Currently there are no licensed therapeutic intervention measures either in terms of vaccines or drugs available for these highly contagious human pathogens. Genetic and antigenic diversity of these viruses, rapid emergence of new strains, and their ability to infect a broad population by using polymorphic histo-blood group antigens for cell attachment, pose significant challenges for the development of effective antiviral agents. Despite these impediments, there is progress in the design and development of therapeutic agents. These include capsid-based candidate vaccines, and potential antivirals either in the form of glycomimetics or designer antibodies that block HBGA binding, as well as those that target essential non-structural proteins such as the viral protease and RNA-dependent RNA polymerase. In addition to these classical approaches, recent studies suggest the possibility of interferons and targeting host cell factors as viable approaches to counter norovirus infection. This review provides a brief overview of this progress. PMID:27318434

  15. Cell-specific targeting of lentiviral vectors mediated by fusion proteins derived from Sindbis virus, vesicular stomatitis virus, or avian sarcoma/leukosis virus

    OpenAIRE

    Marino Michael P; Bialkowska Agnieszka; Kutner Robert H; Zhang Xian-Yang; Klimstra William B; Reiser Jakob

    2010-01-01

    Abstract Background The ability to efficiently and selectively target gene delivery vectors to specific cell types in vitro and in vivo remains one of the formidable challenges in gene therapy. We pursued two different strategies to target lentiviral vector delivery to specific cell types. In one of the strategies, vector particles bearing a membrane-bound stem cell factor sequence plus a separate fusion protein based either on Sindbis virus strain TR339 glycoproteins or the vesicular stomati...

  16. SHuffle, a novel Escherichia coli protein expression strain capable of correctly folding disulfide bonded proteins in its cytoplasm

    Directory of Open Access Journals (Sweden)

    Lobstein Julie

    2012-05-01

    Full Text Available Abstract Background Production of correctly disulfide bonded proteins to high yields remains a challenge. Recombinant protein expression in Escherichia coli is the popular choice, especially within the research community. While there is an ever growing demand for new expression strains, few strains are dedicated to post-translational modifications, such as disulfide bond formation. Thus, new protein expression strains must be engineered and the parameters involved in producing disulfide bonded proteins must be understood. Results We have engineered a new E. coli protein expression strain named SHuffle, dedicated to producing correctly disulfide bonded active proteins to high yields within its cytoplasm. This strain is based on the trxB gor suppressor strain SMG96 where its cytoplasmic reductive pathways have been diminished, allowing for the formation of disulfide bonds in the cytoplasm. We have further engineered a major improvement by integrating into its chromosome a signal sequenceless disulfide bond isomerase, DsbC. We probed the redox state of DsbC in the oxidizing cytoplasm and evaluated its role in assisting the formation of correctly folded multi-disulfide bonded proteins. We optimized protein expression conditions, varying temperature, induction conditions, strain background and the co-expression of various helper proteins. We found that temperature has the biggest impact on improving yields and that the E. coli B strain background of this strain was superior to the K12 version. We also discovered that auto-expression of substrate target proteins using this strain resulted in higher yields of active pure protein. Finally, we found that co-expression of mutant thioredoxins and PDI homologs improved yields of various substrate proteins. Conclusions This work is the first extensive characterization of the trxB gor suppressor strain. The results presented should help researchers design the appropriate protein expression conditions using

  17. Strain-specific antibodies reduce co-feeding transmission of the Lyme disease pathogen, Borrelia afzelii.

    Science.gov (United States)

    Jacquet, Maxime; Durand, Jonas; Rais, Olivier; Voordouw, Maarten J

    2016-03-01

    Vector-borne pathogens use a diversity of strategies to evade the vertebrate immune system. Co-feeding transmission is a potential immune evasion strategy because the vector-borne pathogen minimizes the time spent in the vertebrate host. We tested whether the Lyme disease pathogen, Borrelia afzelii, can use co-feeding transmission to escape the acquired immune response in the vertebrate host. We induced a strain-specific, protective antibody response by immunizing mice with one of two variants of OspC (A3 and A10), the highly variable outer surface protein C of Borrelia pathogens. Immunized mice were challenged via tick bite with B. afzelii strains A3 or A10 and infested with larval ticks at days 2 and 34 post-infection to measure co-feeding and systemic transmission respectively. Antibodies against a particular OspC variant significantly reduced co-feeding transmission of the targeted (homologous) strain but not the non-targeted (heterologous) strain. Cross-immunity between OspC antigens had no effect in co-feeding ticks but reduced the spirochaete load twofold in ticks infected via systemic transmission. In summary, OspC-specific antibodies reduced co-feeding transmission of a homologous but not a heterologous strain of B. afzelii. Co-feeding transmission allowed B. afzelii to evade the negative consequences of cross-immunity on the tick spirochaete load. PMID:26411486

  18. Energetic challenges

    International Nuclear Information System (INIS)

    Full text: Connecting the 2 billion people who have no access to commercial energy is the most important energy challenge facing the world community. Women and children, primarily in developing countries, spend their days collecting wood or cow dung for fuel for cooking and heating their homes in very inefficient stoves: this both harms the environment and directly threatens the health of their families. Outmoded boilers linked to central heating systems in most of the cities of Eastern Europe and the former Soviet Union pose another challenge. They are inefficient; they lack modern pollution control; and the end use of the heat is not metered, leading to more inefficiency and waste. Both of these problems cry out to the world for investment. Investing in energy solutions in these countries can bring about significant and immediate local environmental improvements, achieve greatly improved energy efficiency, and substantially reduce greenhouse gas emissions. But, energy and environmental policy tends to direct investment towards industrial countries, even though it would have a greater impact on the environment - not to mention the human condition in general - in the developing countries and transition economies. We need a new direction in energy policy. The World Energy Council has studied the needs and we believe a number of our proposed policy recommendations would lead towards greater investment in the countries where it is most needed. The political risk of key energy project investments must be addressed both by the countries seeking outside investment and by the global community at large. The countries must create an investor-friendly climate, which includes the rule of law and recognizes private property rights. The global community can contribute by developing new political risk insurance schemes rewarding the countries that create this climate. Energy must be priced to cover costs and ensure payment. In too many countries, blanket subsidies for energy

  19. Development of a Novel Protein Microarray Method for Serotyping Salmonella enterica Strains

    OpenAIRE

    Cai, H.Y.; Lu, L; Muckle, C A; Prescott, J F; Chen, S.

    2005-01-01

    An antibody microarray assay was developed for Salmonella serotyping based on the Kauffmann-White scheme. A model (8 by 15) array was constructed using 35 antibodies for identification of 20 common Salmonella serovars and evaluated using 117 target and 73 nontarget Salmonella strains. The assay allowed complete serovar identification of 86 target strains and partial identification of 30 target strains and allowed exclusion of the 73 nontarget strains from the target serovars.

  20. Featherweight Challenge

    Science.gov (United States)

    Love, Tyler S.; Ryan, Larry

    2012-01-01

    As science, technology education, and engineering programs suffer budget cuts, educators continue to seek cost-effective activities that engage students and reinforce standards. The featherweight challenge is a hands-on activity that challenges students to continually refine their design while not breaking the budget. This activity uses one of the…

  1. Synthetic Biology of Cyanobacteria: Unique Challenges and Opportunities

    Directory of Open Access Journals (Sweden)

    Bertram M Berla

    2013-08-01

    Full Text Available Photosynthetic organisms, and especially cyanobacteria, hold great promise as sources of renewably-produced fuels, bulk and specialty chemicals, and nutritional products. Synthetic biology tools can help unlock cyanobacteria’s potential for these functions, but unfortunately tool development for these organisms has lagged behind that for S. cerevisiae and E. coli. While these organisms may in many cases be more difficult to work with as ‘chassis’ strains for synthetic biology than certain heterotrophs, the unique advantages of autotrophs in biotechnology applications as well as the scientific importance of improved understanding of photosynthesis warrant the development of these systems into something akin to a ‘green E. coli’. In this review, we highlight unique challenges and opportunities for development of synthetic biology approaches in cyanobacteria. We review classical and recently developed methods for constructing targeted mutants in various cyanobacterial strains, and offer perspective on what genetic tools might most greatly expand the ability to engineer new functions in such strains. Similarly, we review what genetic parts are most needed for the development of cyanobacterial synthetic biology. Finally, we highlight recent methods to construct genome-scale models of cyanobacterial metabolism and to use those models to measure properties of autotrophic metabolism. Throughout this paper, we discuss some of the unique challenges of a diurnal, autotrophic lifestyle along with how the development of synthetic biology and biotechnology in cyanobacteria must fit within those constraints.

  2. Xylose Fermentation by Saccharomyces cerevisiae: Challenges and Prospects

    Directory of Open Access Journals (Sweden)

    Danuza Nogueira Moysés

    2016-02-01

    Full Text Available Many years have passed since the first genetically modified Saccharomyces cerevisiae strains capable of fermenting xylose were obtained with the promise of an environmentally sustainable solution for the conversion of the abundant lignocellulosic biomass to ethanol. Several challenges emerged from these first experiences, most of them related to solving redox imbalances, discovering new pathways for xylose utilization, modulation of the expression of genes of the non-oxidative pentose phosphate pathway, and reduction of xylitol formation. Strategies on evolutionary engineering were used to improve fermentation kinetics, but the resulting strains were still far from industrial application. Lignocellulosic hydrolysates proved to have different inhibitors derived from lignin and sugar degradation, along with significant amounts of acetic acid, intrinsically related with biomass deconstruction. This, associated with pH, temperature, high ethanol, and other stress fluctuations presented on large scale fermentations led the search for yeasts with more robust backgrounds, like industrial strains, as engineering targets. Some promising yeasts were obtained both from studies of stress tolerance genes and adaptation on hydrolysates. Since fermentation times on mixed-substrate hydrolysates were still not cost-effective, the more selective search for new or engineered sugar transporters for xylose are still the focus of many recent studies. These challenges, as well as under-appreciated process strategies, will be discussed in this review.

  3. Xylose Fermentation by Saccharomyces cerevisiae: Challenges and Prospects.

    Science.gov (United States)

    Moysés, Danuza Nogueira; Reis, Viviane Castelo Branco; de Almeida, João Ricardo Moreira; de Moraes, Lidia Maria Pepe; Torres, Fernando Araripe Gonçalves

    2016-01-01

    Many years have passed since the first genetically modified Saccharomyces cerevisiae strains capable of fermenting xylose were obtained with the promise of an environmentally sustainable solution for the conversion of the abundant lignocellulosic biomass to ethanol. Several challenges emerged from these first experiences, most of them related to solving redox imbalances, discovering new pathways for xylose utilization, modulation of the expression of genes of the non-oxidative pentose phosphate pathway, and reduction of xylitol formation. Strategies on evolutionary engineering were used to improve fermentation kinetics, but the resulting strains were still far from industrial application. Lignocellulosic hydrolysates proved to have different inhibitors derived from lignin and sugar degradation, along with significant amounts of acetic acid, intrinsically related with biomass deconstruction. This, associated with pH, temperature, high ethanol, and other stress fluctuations presented on large scale fermentations led the search for yeasts with more robust backgrounds, like industrial strains, as engineering targets. Some promising yeasts were obtained both from studies of stress tolerance genes and adaptation on hydrolysates. Since fermentation times on mixed-substrate hydrolysates were still not cost-effective, the more selective search for new or engineered sugar transporters for xylose are still the focus of many recent studies. These challenges, as well as under-appreciated process strategies, will be discussed in this review. PMID:26927067

  4. Xylose Fermentation by Saccharomyces cerevisiae: Challenges and Prospects

    Science.gov (United States)

    Moysés, Danuza Nogueira; Reis, Viviane Castelo Branco; de Almeida, João Ricardo Moreira; de Moraes, Lidia Maria Pepe; Torres, Fernando Araripe Gonçalves

    2016-01-01

    Many years have passed since the first genetically modified Saccharomyces cerevisiae strains capable of fermenting xylose were obtained with the promise of an environmentally sustainable solution for the conversion of the abundant lignocellulosic biomass to ethanol. Several challenges emerged from these first experiences, most of them related to solving redox imbalances, discovering new pathways for xylose utilization, modulation of the expression of genes of the non-oxidative pentose phosphate pathway, and reduction of xylitol formation. Strategies on evolutionary engineering were used to improve fermentation kinetics, but the resulting strains were still far from industrial application. Lignocellulosic hydrolysates proved to have different inhibitors derived from lignin and sugar degradation, along with significant amounts of acetic acid, intrinsically related with biomass deconstruction. This, associated with pH, temperature, high ethanol, and other stress fluctuations presented on large scale fermentations led the search for yeasts with more robust backgrounds, like industrial strains, as engineering targets. Some promising yeasts were obtained both from studies of stress tolerance genes and adaptation on hydrolysates. Since fermentation times on mixed-substrate hydrolysates were still not cost-effective, the more selective search for new or engineered sugar transporters for xylose are still the focus of many recent studies. These challenges, as well as under-appreciated process strategies, will be discussed in this review. PMID:26927067

  5. Numerical demonstration of MEMS strain sensor

    Science.gov (United States)

    Saboonchi, Hossain; Ozevin, Didem

    2012-04-01

    Silicon has piezoresistive property that allows designing strain sensor with higher gauge factor compared to conventional metal foil gauges. The sensing element can be micro-scale using MEMS, which minimizes the effect of strain gradient on measurement at stress concentration regions such as crack tips. The challenge of MEMS based strain sensor design is to decouple the sensing element from substrate for true strain measurement and to compensate the temperature effect on the piezoresistive coefficients of silicon. In this paper, a family of MEMS strain sensors with different geometric designs is introduced. Each strain sensor is made of single crystal silicon and manufactured using deposition/ etching/oxidation steps on a n- doped silicon wafer in (100) plane. The geometries include sensing element connected to the free heads of U shape substrate, a set of two or more sensing elements in an array in order to capture strain gradients and two directional sensors. The response function and the gauge factor of the strain sensors are identified using multi-physics models that combine structural and electrical behaviors of sensors mounted on a strained structure. The relationship between surface strain and strain at microstructure is identified numerically in order to include the relationship in the response function calculation.

  6. Study on the Preservation Methods for Rabbit Pasteurella multocida C51-17 Strain Challenging in Inactivated Vaccine Potency Test%兔多杀性巴氏杆菌C51-17株在疫苗效力检验中保存方法的研究

    Institute of Scientific and Technical Information of China (English)

    张媛; 李建; 张磊; 王秀丽; 张立春; 丁家波

    2014-01-01

    Pasteurella multocida strain C51-17 was required as the challenging strain in the assessment for the potency of rabbit Pasteurella multocida inactivated vaccine. In order to ensure the exactly challenging dosage, viable count for the bacteria liquid culture should be done before challenging to rabbits, which procedure was called pre-estimating. Traditional methods of pre-estimating viable count for the bacteria liquid culture were calculating bacteria survival rate stocked in 4℃ or measuring the culture absorption value. In this study, bacteria liquid culture was divided into portions and stocked in -80 ℃ as the challenging bacteria. These three kinds of dealing samples were used for pre-estimating viable count to compare the bacteria stability and vitality. The results indicated that bacteria liquid culture frozen in -80 ℃kept the best vitality and had good reproducibility, and it accorded with the challenging amount in the further viable count test. The bacteria culture dealt by this way could make the control established in each time in Pasteurella multocida inactivated vaccine potency test. Therefore, the method can be used to pre-estimating viable count of bacteria liquid culture for challenging in rabbit Pasteurella multocida inactivated vaccine potency test.%通过将兔多杀性巴氏杆菌C51-17株菌液分装后置-80℃冻存的方法对菌液浓度进行预数,并与传统方法采用的将菌液置4℃保存过夜计算菌存率或通过测定菌液吸光值推算攻毒菌液浓度相比较。结果表明,用-80℃冻存保存方法估算的菌液浓度与实际浓度更接近,采用这种方法进行疫苗的效力检验,能确保对照成立,在兔多杀性巴氏杆菌病灭活疫苗效力检验中可以采用-80℃冻存的方法进行攻毒菌液的预数。

  7. Geobacteraceae strains and methods

    Science.gov (United States)

    Lovley, Derek R.; Nevin, Kelly P.; Yi, Hana

    2015-07-07

    Embodiments of the present invention provide a method of producing genetically modified strains of electricigenic microbes that are specifically adapted for the production of electrical current in microbial fuel cells, as well as strains produced by such methods and fuel cells using such strains. In preferred embodiments, the present invention provides genetically modified strains of Geobacter sulfurreducens and methods of using such strains.

  8. Borrelia burgdorferi strain-specific Osp C-mediated immunity in mice.

    Science.gov (United States)

    Bockenstedt, L K; Hodzic, E; Feng, S; Bourrel, K W; de Silva, A; Montgomery, R R; Fikrig, E; Radolf, J D; Barthold, S W

    1997-11-01

    Antibodies to the outer surface proteins (Osps) A, B, and C of the spirochete Borrelia burgdorferi can prevent infection in animal models of Lyme borreliosis. We have previously demonstrated that immune serum from mice infected with B. burgdorferi N40 can also prevent challenge infection and induce disease regression in infected mice. The antigens targeted by protective and disease-modulating antibodies are presently unknown, but they do not include Osp A or Osp B. Because Osp C antibodies are present in immune mouse serum, we investigated the ability of hyperimmune serum to recombinant Osp C (N40) to protect mice against challenge infection with N40 spirochetes. In both active and passive immunization studies, Osp C (N40) antiserum failed to protect mice from challenge infection with cultured organisms. Mice actively immunized with recombinant Osp C (N40) were susceptible to tick-borne challenge infection, and nymphal ticks remained infected after feeding on Osp C-hyperimmunized mice. In contrast, similar immunization studies performed with Osp C (PKo) antiserum prevented challenge infection of mice with a clone of PKo spirochetes pathogenic for mice. Both Osp C (N40) and Osp C (PKo) antisera showed minimal in vitro borreliacidal activity, and immunofluorescence studies localized Osp C beneath the outer membrane of both N40 and PKo spirochetes. We conclude that Osp C antibody-mediated immunity is strain specific and propose that differences in Osp C surface expression by spirochetes in vivo may account for strain-specific immunity. PMID:9353047

  9. Cross protection among Haemophilus parasuis strains in immunized gnotobiotic pigs.

    OpenAIRE

    Miniats, O. P.; Smart, N L; Rosendal, S

    1991-01-01

    In an attempt to establish if cross protection can be induced by different strains of Haemophilus parasuis, three groups of 12 gnotobiotic pigs were immunized each with an aluminum hydroxide adsorbed whole cell bacterin of one of three H. parasuis strains. Two weeks later, four pigs within each vaccinated group were challenged with aerosols of live cultures of each of the three test strains and observed for response. Two virulent strains V1 and V2 protected all the vaccinated pigs, while all ...

  10. Muscle strain (image)

    Science.gov (United States)

    A muscle strain is the stretching or tearing of muscle fibers. A muscle strain can be caused by sports, exercise, a ... something that is too heavy. Symptoms of a muscle strain include pain, tightness, swelling, tenderness, and the ...

  11. Muscle strain treatment

    Science.gov (United States)

    Treatment - muscle strain ... Question: How do you treat a muscle strain ? Answer: Rest the strained muscle and apply ice for the first few days after the injury. Anti-inflammatory medicines or acetaminophen ( ...

  12. Oral administration of a select mixture of Bacillus probiotics generates Tr1 cells in weaned F4ab/acR pigs challenged with an F4+ ETEC/VTEC/EPEC strain

    DEFF Research Database (Denmark)

    Zhou, Dong; Zhang, Wei; Wang, Meng-Ling;

    2015-01-01

    ) − positive ETEC/VTEC/EPEC challenge. Administration of BLS-mix increased the percentage of Foxp3−IL-10+ T cells but not of Foxp3+IL-10+ regulatory T (Treg) cells among peripheral blood CD4+ T cells. A low dose of BLS-mix feeding resulted in increased the expression of IL-6, TNF-α, IL-10, and the...... transcription factors Foxp3 and T-bet mRNAs in the jejunum. Administration of either a low or high dose BLS-mix also led to an increase in the percentage of CD4+Foxp3+ Treg cells among intraepithelial lymphocytes and CD4+IL-10+ T cells in the small intestinal Peyer’s patches and the lamina propria of F4ab....../acR− pigs following F4+ ETEC/VTEC/EPEC challenge. The increased number of IL-10–producing CD4+ T cells was attributed to an increase in the proportion of Foxp3−IL-10+ Treg cells rather than Foxp3+IL-10+ Treg cells. Our data indicate that oral administration of BLS-mix to newly weaned F4ab/acR− pigs...

  13. Experimental foreign body infections in mice challenged with slime-producing Staphylococcus epidermidis.

    OpenAIRE

    Christensen, G D; Simpson, W A; Bisno, A L; Beachey, E H

    1983-01-01

    The virulence of two previously described Staphylococcus epidermidis strains was examined in an experimental model of foreign body infection in mice. Animals challenged with the slime-producing strain developed three times as many infections as animals challenged with the strain that did not produce slime (P less than 0.001). Bacterial isolates recovered from the infected sites retained the characteristics of the inoculated strain. Animals without foreign bodies but challenged in a similar ma...

  14. Logistical challenges

    Directory of Open Access Journals (Sweden)

    Steve Matthews

    2005-07-01

    Full Text Available The impact of the Asian tsunami was unprecedented and the logistical challenges of meeting the needs of those affected were enormous. Had the tsunami happened even five years ago, World Vision would not have been able to respond nearly as effectively as it did.

  15. Mobility Challenges

    DEFF Research Database (Denmark)

    Jensen, Ole B.; Lassen, Claus

    2011-01-01

    This article takes point of departure in the challenges to understand the importance of contemporary mobility. The approach advocated is a cross-disciplinary one drawing on sociology, geography, urban planning and design, and cultural studies. As such the perspective is to be seen as a part of th...

  16. Ethical Challenges

    Science.gov (United States)

    Morris, Michael

    2004-01-01

    All evaluators face the challenge of striving to adhere to the highest possible standards of ethical conduct. Translating the AEA's Guiding Principles and the Joint Committee's Program Evaluation Standards into everyday practice, however, can be a complex, uncertain, and frustrating endeavor. Moreover, acting in an ethical fashion can require…

  17. Editorial Challenges

    OpenAIRE

    Budin, Wendy C.

    2008-01-01

    In this column, the editor of The Journal of Perinatal Education (JPE) discusses some of the challenges involved in becoming the new editor of JPE. The editor also describes the contents of this issue, which offer a broad range of resources, research, and inspiration for childbirth educators in their efforts to promote normal birth.

  18. Archiving challenges

    OpenAIRE

    Ringersma, J.

    2010-01-01

    Teaching slides on: What is a digital archive? Parties involved in digital archiving Archiving challenges organization of data coherence and persistency access and safety Language archiving software Different users, different needs For: Saami Language Documentation and Revitalization. Winter school, Bodø, Norway

  19. Challenges in obesity research.

    Science.gov (United States)

    Palou, Andreu; Bonet, M Luisa

    2013-09-01

    Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors--often interrelated and many of them still unknown or poorly understood--can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity. PMID:24010755

  20. Challenges in obesity research

    Directory of Open Access Journals (Sweden)

    Andreu Palou

    2013-09-01

    Full Text Available Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors -often interrelated and many of them still unknown or poorly understood- can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity.

  1. Nanocomposite Strain Gauges Having Small TCRs

    Science.gov (United States)

    Gregory, Otto; Chen, Ximing

    2009-01-01

    Ceramic strain gauges in which the strain-sensitive electrically conductive strips made from nanocomposites of noble metal and indium tin oxide (ITO) are being developed for use in gas turbine engines and other power-generation systems in which gas temperatures can exceed 1,500 F (about 816 C). In general, strain gauges exhibit spurious thermally induced components of response denoted apparent strain. When temperature varies, a strain-gauge material that has a nonzero temperature coefficient of resistance (TCR) exhibits an undesired change in electrical resistance that can be mistaken for the change in resistance caused by a change in strain. It would be desirable to formulate straingauge materials having TCRs as small as possible so as to minimize apparent strain. Most metals exhibit positive TCRs, while most semiconductors, including ITO, exhibit negative TCRs. The present development is based on the idea of using the negative TCR of ITO to counter the positive TCRs of noble metals and of obtaining the benefit of the ability of both ITO and noble metals to endure high temperatures. The noble metal used in this development thus far has been platinum. Combinatorial libraries of many ceramic strain gauges containing nanocomposites of various proportions of ITO and platinum were fabricated by reactive co-sputtering from ITO and platinum targets onto alumina- and zirconia-based substrates mounted at various positions between the targets.

  2. CERN: Fixed target targets

    International Nuclear Information System (INIS)

    Full text: While the immediate priority of CERN's research programme is to exploit to the full the world's largest accelerator, the LEP electron-positron collider and its concomitant LEP200 energy upgrade (January, page 1), CERN is also mindful of its long tradition of diversified research. Away from LEP and preparations for the LHC proton-proton collider to be built above LEP in the same 27-kilometre tunnel, CERN is also preparing for a new generation of heavy ion experiments using a new source, providing heavier ions (April 1992, page 8), with first physics expected next year. CERN's smallest accelerator, the LEAR Low Energy Antiproton Ring continues to cover a wide range of research topics, and saw a record number of hours of operation in 1992. The new ISOLDE on-line isotope separator was inaugurated last year (July, page 5) and physics is already underway. The remaining effort concentrates around fixed target experiments at the SPS synchrotron, which formed the main thrust of CERN's research during the late 1970s. With the SPS and LEAR now approaching middle age, their research future was extensively studied last year. Broadly, a vigorous SPS programme looks assured until at least the end of 1995. Decisions for the longer term future of the West Experimental Area of the SPS will have to take into account the heavy demand for test beams from work towards experiments at big colliders, both at CERN and elsewhere. The North Experimental Area is the scene of larger experiments with longer lead times. Several more years of LEAR exploitation are already in the pipeline, but for the longer term, the ambitious Superlear project for a superconducting ring (January 1992, page 7) did not catch on. Neutrino physics has a long tradition at CERN, and this continues with the preparations for two major projects, the Chorus and Nomad experiments (November 1991, page 7), to start next year in the West Area. Delicate neutrino oscillation effects could become

  3. CHALLENGES IN BRONCHIAL CHALLENGE TESTING

    NARCIS (Netherlands)

    Lexmond, A. J.; Hagedoorn, P.; Frijlink, H. W.; de Boer, A. H.

    2013-01-01

    Background: In the adenosine 5'-monophosphate (AMP) bronchial challenge test, AMP is usually administered according to dosing protocols developed for histamine/methacholine. It has never been thoroughly investigated whether these protocols are suitable for AMP as well. Methods: The setup of the two-

  4. Program Calibrates Strain Gauges

    Science.gov (United States)

    Okazaki, Gary D.

    1991-01-01

    Program dramatically reduces personnel and time requirements for acceptance tests of hardware. Data-acquisition system reads output from Wheatstone full-bridge strain-gauge circuit and calculates strain by use of shunt calibration technique. Program nearly instantaneously tabulates and plots strain data against load-cell outputs. Modified to acquire strain data for other specimens wherever full-bridge strain-gauge circuits used. Written in HP BASIC.

  5. Sputter target

    Science.gov (United States)

    Gates, Willard G.; Hale, Gerald J.

    1980-01-01

    The disclosure relates to an improved sputter target for use in the deposition of hard coatings. An exemplary target is given wherein titanium diboride is brazed to a tantalum backing plate using a gold-palladium-nickel braze alloy.

  6. Challenges in Soft Tissue Engineering

    OpenAIRE

    Yuksel, Eser; Choo, Joshua; Wettergreen, Matthew; Liebschner, Michael

    2005-01-01

    Soft tissue engineering strategies targeting restoration of volume loss have inherent critical challenges as they relate to the problem of restoration of defects with a high volume to surface ratio. We outline the problems associated with the limitations of translational applications regarding soft tissue engineering strategies as follows: cell survival, mechanical challenges: macroenvironment (scaffold collapse and on-the-shelf availability), compositional considerations: microenvironment, i...

  7. Global challenges

    International Nuclear Information System (INIS)

    A major challenge now facing the world is the supply of energy needed for growth and development in a manner which is not only economically viable but also environmentally acceptable and sustainable in view of the demands of and risks to future generations. The internationally most significant pollutants from energy production through fossil fuels are SO2 and NOx which cause acid rain, and CO2 which is the most significant contributor to the greenhouse effect. Nuclear power, now providing about 17% of the world's electricity and 5% of the primary energy already is making a notable contribution to avoiding these emissions. While the industrialized countries will need more energy and especially electricity in the future, the needs of the developing countries are naturally much larger and present a tremendous challenge to the shaping of the world's future energy supply system. The advanced countries will have to accept special responsibilities, as they can most easily use advanced technologies and they have been and remain the main contributors to the environmental problems we now face. Energy conservation and resort to new renewable energy sources, though highly desirable, appear inadequate alone to meet the challenges. The world can hardly afford to do without an increased use of nuclear power, although it is strongly contested in many countries. The objections raised against the nuclear option focus on safety, waste management and disposal problems and the risk for proliferation of nuclear weapons. These issues are not without their problems. The risk of proliferation exists but will not appreciably diminish with lesser global reliance on nuclear power. The waste issue is more of a political than a technical problem. The use of nuclear power, or any other energy source, will never be at zero risk, but the risks are constantly reduced by new techniques and practices. The IAEA sees it as one of its priority tasks to promote such techniques. (author)

  8. Challenging the state-of-the-art in protein structure prediction: Highlights of experimental target structures for the 10th Critical Assessment of Techniques for Protein Structure Prediction Experiment CASP10

    OpenAIRE

    Kryshtafovych, Andriy; Moult, John; Bales, Patrick; Bazan, J. Fernando; Biasini, Marco; Burgin, Alex; Chen, Chen; Cochran, Frank V; Craig, Timothy K.; Das, Rhiju; Fass, Deborah; Garcia-Doval, Carmela; Herzberg, Osnat; Lorimer, Donald; Luecke, Hartmut

    2014-01-01

    For the last two decades, CASP has assessed the state of the art in techniques for protein structure prediction and identified areas which required further development. CASP would not have been possible without the prediction targets provided by the experimental structural biology community. In the latest experiment, CASP10, over 100 structures were suggested as prediction targets, some of which appeared to be extraordinarily difficult for modeling. In this paper, authors of some of the most ...

  9. Data Challenges

    CERN Multimedia

    McCubbin, N A

    Some two years ago we planned a series of Data Challenges starting at the end of 2001. At the time, that seemed to be comfortingly far in the future... Well, as the saying goes, doesn't time fly when you are having fun! ATLAS Computing is now deep in the throes of getting the first Data Challenge (DC0) up and running. One of the main aims of DC0 is to have a software 'release' in which we can generate full physics events, track all particles through the detector, simulate the detector response, reconstruct the event, and study it, with appropriate data storage en route. As all software is "always 95% ready" (!), we have been able to do most of this, more or less, for some time. But DC0 forces us to have everything working, together, at the same time: a reality check. DC0 should finish early next year, and it will be followed almost immediately afterwards by DC1 (DC0 was foreseen as the 'check' for DC1). DC1 will last into the middle of 2002, and has two major goals. The first is generation, simulation, and r...

  10. A Natural Vaccine Candidate Strain Against Cholera

    Institute of Scientific and Technical Information of China (English)

    LIUYAN-QING; QIGUO-MING; 等

    1995-01-01

    El Tor Vibrio cholerae(EVC)strains may be classified into two kinds-epidemigenic(EEVC)strains and non-epidemigenic(NEEVC)strains-based on a phage-biotyping system.A large number of EEVC strains have been screened for toxigenic and putative colonization attributes.One such naturally occurring strain(designated IEM101)has been found which is devoid of genes encoding cholera toxin(CT),accessory cholera enterotoxin(ACE),zonula occludens toxin(ZOT),but possesses RS1 sequences and toixn-coregulated pilus A gene(tcpA)although tcpA is poorly expressed.It expresses type B pili but does not posses type C pili.It is an El Tor Ogawa strain and does not cause fluid accumulation in rabbit ileal loop tests.Active immunization of rabbits with strain IEM101 elicited good protection against challenge with virulent strains of V.cholerae Ol.Oral administration cased no side effects in 15 human volunteers.colonized the gut for four to ten days and elicited good immune responses.

  11. Target capture and target ghosts

    Science.gov (United States)

    Auerbach, Steven P.

    1996-05-01

    Optimal detection methods for small targets rely on whitened matched filters, which convolve the measured data with the signal model, and whiten the result with the noise covariance. In real-world implementations of such filters, the noise covariance must be estimated from the data, and the resulting covariance estimate may be corrupted by presence of the target. The resulting loss in SNR is called 'target capture'. Target capture is often thought to be a problem only for bright targets. This presentation shows that target capture also arises for dim targets, leading to an SNR loss which is independent of target strength and depends on the averaging method used to estimate the noise covariance. This loss is due to a 'coherent beat' between the true noise and that portion of the estimated noise covariance due to the target. This beat leads to 'ghost targets', which diminish the target SNR by producing a negative target ghost at the target's position. A quantitative estimate of this effect will be given, and shown to agree with numerical results. The effect of averaging on SNR is also discussed for data scenes with synthetic injected targets, in cases where the noise covariance is estimated using 'no target' data. For these cases, it is shown that the so-called 'optimal' filter, which uses the true noise covariance, is actually worse than a 'sub-optimal' filter which estimates the noise from scene. This apparent contradiction is resolved by showing that the optimal filter is best if the same filter is used for many scenes, but is outperformed by a filter adapted to a specific scene.

  12. The principle of strain reconstruction tomography: Determination of quench strain distribution from diffraction measurements

    International Nuclear Information System (INIS)

    The evaluation of residual elastic strain within the bulk of engineering components or natural objects is a challenging task, since in general it requires mapping a six-component tensor quantity in three dimensions. A further challenge concerns the interpretation of finite resolution data in a way that is commensurate and non-contradictory with respect to continuum deformation models. A practical solution for this problem, if it is ever to be found, must include efficient measurement interpretation and data reduction techniques. We describe the principle of strain tomography by high-energy X-ray diffraction, i.e. reconstruction of the higher dimensional distribution of strain within an object from multiple scans in lower dimensions, and illustrate the application of this principle to a simple case of reconstruction of an axisymmetric residual strain state induced in a cylindrical sample by quenching. The underlying principle of the analysis method presented in this paper allows generalisation to more complex situations

  13. The principle of strain reconstruction tomography: Determination of quench strain distribution from diffraction measurements

    Energy Technology Data Exchange (ETDEWEB)

    Korsunsky, Alexander M. [Department of Engineering Science, University of Oxford, Parks Road, Oxford, Oxon OX1 3PJ (United Kingdom)]. E-mail: alexander.korsunsky@eng.ox.ac.uk; Vorster, Willem J.J. [Department of Engineering Science, University of Oxford, Parks Road, Oxford, Oxon OX1 3PJ (United Kingdom); Zhang, Shu Yan [Department of Engineering Science, University of Oxford, Parks Road, Oxford, Oxon OX1 3PJ (United Kingdom); Dini, Daniele [Department of Engineering Science, University of Oxford, Parks Road, Oxford, Oxon OX1 3PJ (United Kingdom); Latham, David [Department of Engineering Science, University of Oxford, Parks Road, Oxford, Oxon OX1 3PJ (United Kingdom); Golshan, Mina [Synchrotron Radiation Source, Daresbury Laboratory, Keckwick Lane, Warrington WA4 4AD (United Kingdom); Liu, Jian [Department of Chemistry, University of Durham, South Road, Durham DH1 3LE (United Kingdom); Kyriakoglou, Yannis [Rolls-Royce plc, P.O. Box 31, Derby DE24 8BJ (United Kingdom); Walsh, Michael J. [Rolls-Royce plc, P.O. Box 31, Derby DE24 8BJ (United Kingdom)

    2006-05-15

    The evaluation of residual elastic strain within the bulk of engineering components or natural objects is a challenging task, since in general it requires mapping a six-component tensor quantity in three dimensions. A further challenge concerns the interpretation of finite resolution data in a way that is commensurate and non-contradictory with respect to continuum deformation models. A practical solution for this problem, if it is ever to be found, must include efficient measurement interpretation and data reduction techniques. We describe the principle of strain tomography by high-energy X-ray diffraction, i.e. reconstruction of the higher dimensional distribution of strain within an object from multiple scans in lower dimensions, and illustrate the application of this principle to a simple case of reconstruction of an axisymmetric residual strain state induced in a cylindrical sample by quenching. The underlying principle of the analysis method presented in this paper allows generalisation to more complex situations.

  14. Harnessing functional food strategies for the health challenges of space travel—Fermented soy for astronaut nutrition

    Science.gov (United States)

    Buckley, Nicole D.; Champagne, Claude P.; Masotti, Adriana I.; Wagar, Lisa E.; Tompkins, Thomas A.; Green-Johnson, Julia M.

    2011-04-01

    Astronauts face numerous health challenges during long-duration space missions, including diminished immunity, bone loss and increased risk of radiation-induced carcinogenesis. Changes in the intestinal flora of astronauts may contribute to these problems. Soy-based fermented food products could provide a nutritional strategy to help alleviate these challenges by incorporating beneficial lactic acid bacteria, while reaping the benefits of soy isoflavones. We carried out strain selection for the development of soy ferments, selecting strains of lactic acid bacteria showing the most effective growth and fermentation ability in soy milk ( Streptococcus thermophilus ST5, Bifidobacterium longum R0175 and Lactobacillus helveticus R0052). Immunomodulatory bioactivity of selected ferments was assessed using an in vitro challenge system with human intestinal epithelial and macrophage cell lines, and selected ferments show the ability to down-regulate production of the pro-inflammatory cytokine interleukin-8 following challenge with tumour necrosis factor-alpha. The impact of fermentation on vitamin B1 and B6 levels and on isoflavone biotransformation to agluconic forms was also assessed, with strain variation-dependent biotransformation ability detected. Overall this suggests that probiotic bacteria can be successfully utilized to develop soy-based fermented products targeted against health problems associated with long-term space travel.

  15. Strains and Sprains

    Science.gov (United States)

    ... ON THIS TOPIC Sports Medicine Center Preventing Children's Sports Injuries Computer-Related Repetitive Stress Injuries Knee Injuries Broken ... Knee Injuries Sports and Exercise Safety Dealing With Sports Injuries Groin Strain Ankle Sprains Strains and Sprains Stretching ...

  16. Strained Silicon Photonics

    OpenAIRE

    Wehrspohn, Ralf B; Jörg Schilling; Christian Bohley; Clemens Schriever

    2012-01-01

    A review of recent progress in the field of strained silicon photonics is presented. The application of strain to waveguide and photonic crystal structures can be used to alter the linear and nonlinear optical properties of these devices. Here, methods for the fabrication of strained devices are summarized and recent examples of linear and nonlinear optical devices are discussed. Furthermore, the relation between strain and the enhancement of the second order nonlinear susceptibility is inves...

  17. SPS Challenges

    CERN Document Server

    Chapochnikova, Elena

    2008-01-01

    In future the SPS should be able to transfer to the LHC the beam produced by a completely new pre-injector chain and required by the LHC for different upgrade scenarios. The issues related to this extremely challenging task are presented together with some possible ways of overcoming the problems that arise. Besides an increase in injection energy provided by PS2, these measures can include both an SPS vacuum chamber upgrade against the e-cloud and operation with larger longitudinal emittance for beam stability. As a result the power plant of the SPS RF system must be doubled. The SPS upgrade will also need the improvement or replacement of many other machine elements.

  18. Challenges to 5G standardization

    DEFF Research Database (Denmark)

    Mihovska, Albena D.; Prasad, Ramjee

    2013-01-01

    Interoperable, ubiquitous and dynamic are key objectives for fifth-generation (5G) communication systems and applications. These characteristics are also at the core of the main challenges that researchers, manufacturers, regulators and standardization bodies face when designing targeted strategies...... for the successful deployment of 5G enabling technologies....

  19. Training Information Consumers: Today's Challenge.

    Science.gov (United States)

    Gordon, Dena W.

    The revolution in the information environment caused by new technology is making the training of information consumers a major challenge for publishers of business-targeted databases and vendors of online systems. Research conducted by Data Courier in 1981 and 1982 suggests that online searching by information consumers will continue to increase.…

  20. The Sinuous Target

    Energy Technology Data Exchange (ETDEWEB)

    Zwaska, R. [Fermilab

    2015-06-01

    We report on the concept for a target material comprised of a multitude of interlaced wires of small dimension. This target material concept is primarily directed at high-power neutrino targets where the thermal shock is large due to small beam sizes and short durations; it also has applications to other high-power targets, particularly where the energy deposition is great or a high surface area is preferred. This approach ameliorates the problem of thermal shock by engineering a material with high strength on the micro-scale, but a very low modulus of elasticity on the meso-scale. The low modulus of elasticity is achieved by constructing the material of spring-like wire segments much smaller than the beam dimension. The intrinsic bends of the wires will allow them to absorb the strain of thermal shock with minimal stress. Furthermore, the interlaced nature of the wires provides containment of any segment that might become loose. We will discuss the progress on studies of analogue materials and fabrication techniques for sinuous target materials.

  1. Growth Inhibition of Re-Challenge B16 Melanoma Transplant by Conjugates of Melanogenesis Substrate and Magnetite Nanoparticles as the Basis for Developing Melanoma-Targeted Chemo-Thermo-Immunotherapy

    Directory of Open Access Journals (Sweden)

    Tomoaki Takada

    2009-01-01

    Full Text Available Melanogenesis substrate, N-propionyl-cysteaminylphenol (NPrCAP, is selectively incorporated into melanoma cells and inhibits their growth by producing cytotoxic free radicals. Magnetite nanoparticles also disintegrate cancer cells and generate heat shock protein (HSP upon exposure to an alternating magnetic field (AMF. This study tested if a chemo-thermo-immunotherapy (CTI therapy strategy can be developed for better management of melanoma by conjugating NPrCAP on the surface of magnetite nanoparticles (NPrCAP/M. We examined the feasibility of this approach in B16 mouse melanoma and evaluated the impact of exposure temperature, frequency, and interval on the inhibition of re-challenged melanoma growth. The therapeutic protocol against the primary transplanted tumor with or without AMF exposure once a day every other day for a total of three treatments not only inhibited the growth of the primary transplant but also prevented the growth of the secondary, re-challenge transplant. The heat-generated therapeutic effect was more significant at a temperature of 43∘C than either 41∘C or 46∘C. NPrCAP/M with AMF exposure, instead of control magnetite alone or without AMF exposure, resulted in the most significant growth inhibition of the re-challenge tumor and increased the life span of the mice. HSP70 production was greatest at 43∘C compared to that with 41∘C or 46∘C. CD+T cells were infiltrated at the site of the re-challenge melanoma transplant.

  2. Scrapheap Challenge

    CERN Multimedia

    2004-01-01

    Three British guys at CERN recently took a break from work to try their hand at Scrapheap Challenge. Shown on Channel 4 in the UK, it is a show where two teams must construct a machine for a specific task using only the junk they can scavenge from the scrap yard around them. And they have just 10 hours to build their contraption before it is put to the test. The first round, aired 19 September, pitted a team of three women, from the British Army's Royal Electrical and Mechanical Engineers, against the CERN guys - the Up 'n Atoms: Ali Day, David McFarlane and James Ridewood. Each team, with the help of an appointed expert, had the task of making a giant, 3-metre self-propelled "bowling ball", to roll down a 50 metre bowling alley at skittles 4 metres high. The Up 'n Atoms' contraption featured a small car with a huge wheel on its back. Once up to speed, slamming on the brakes caused the wheel to roll over and take the car with it. On their very last run they managed to take out seven pins. Luckily, though, ...

  3. MicroRNA Targets - How to predict?

    OpenAIRE

    Das, Nabajit

    2012-01-01

    A number of web tools are available for the prediction and identification of target microRNAs (miRNAs). The choice, availability, validity and selection of an optimal yet appropriate tool are a challenge for the design of high throughput assays with promising miRNA targets. The current trends and challenges for target microRNAs (miRNAs) prediction, identification and selection is described in this review.

  4. Antiproton Target

    CERN Multimedia

    1980-01-01

    Antiproton target used for the AA (antiproton accumulator). The first type of antiproton production target used from 1980 to 1982 comprised a rod of copper 3mm diameter and 120mm long embedded in a graphite cylinder that was itself pressed into a finned aluminium container. This assembly was air-cooled and it was used in conjunction with the Van der Meer magnetic horn. In 1983 Fermilab provided us with lithium lenses to replace the horn with a view to increasing the antiproton yield by about 30%. These lenses needed a much shorter target made of heavy metal - iridium was chosen for this purpose. The 50 mm iridium rod was housed in an extension to the original finned target container so that it could be brought very close to the entrance to the lithium lens. Picture 1 shows this target assembly and Picture 2 shows it mounted together with the lithium lens. These target containers had a short lifetime due to a combination of beam heating and radiation damage. This led to the design of the water-cooled target in...

  5. Strain Monitoring of Flexible Structures

    Science.gov (United States)

    Litteken, Douglas A.

    2017-01-01

    , such as tensile testing, fatigue testing, and shear testing, but common measurement techniques cannot be used on fabric. Measuring strain in a material and during a test is a critical parameter for an engineer to monitor the structure during the test and correlate to an analytical model. The ability to measure strain in fabric structures is a challenge for NASA. Foil strain gauges, for example, are commonplace on metallic structures testing, but are extremely difficult to interface with a fabric substrate. New strain measuring techniques need to be developed for use with fabric structures. This paper investigates options for measuring strain in fabric structures for both ground testing and in-space structural health monitoring. It evaluates current commercially available options and outlines development work underway to build custom measurement solutions for NASA's fabric structures.

  6. The Uses and Future Prospects of Metabolomics and Targeted Metabolite Profiling in Cell Factory Development

    DEFF Research Database (Denmark)

    Harrison, Scott James; Herrgard, Markus

    2013-01-01

    The development of cell factories for the production of chemicals has traditionally relied on measurements of product metabolite titers to assess the performance of genetically manipulated strains. With the development of improved metabolomics and targeted metabolite profiling methods, these...... broader measurements of the cellular metabolic state are now becoming part of the toolbox used to characterize cell factories. In this review we briefly summarize the benefits and challenges of global metabolomics and targeted metabolite profiling methods and discuss the application of these methods in...... both pathway discovery and cell factory engineering. We focus particularly on exploring the potential of global metabolomics to complement more traditional targeted methods. We conclude the review by discussing emerging trends in metabolomics and how these developments can aid the engineering of better...

  7. Regulatory challenges

    International Nuclear Information System (INIS)

    The problem for policy makers wanting to liberalize natural gas markets is that its concentrated structure may also be the socially most efficient one. Because of scale economies, more firms operating in the market may incur higher transportation costs unless the market grows sufficiently in each geographic segment. This argument goes for product extension through vertical (or horizontal) integration and the exploitation of economies of scope as well. Thus, the challenge for governments is to intervene in a way that preserves a market structure that has the potential to minimize cost, and at the same lime change its behavior in order to avoid possible lax cost control and exploitation of market power. The existence of scope advantages indicates that liberalization of the market should open for the possibility to bundle services in competition with provision of unbundled services. If operations are unbundled and there exist economies of scope, the gain from increased competition should be weighed against the losses of less efficient operations of each firm. Thus, with the growth in the European market, gradually more arguments support the idea of unbundling. The significant scale economy in trunk pipelines, sunk investments and capital immobility, possible economies of scope in vertical integration and companies' bundling of services influences vertical and horizontal ownership relations and contractual terms in the European gas market. In specific segments of the markets, these relationships may promote efficient investments and pricing without public interference, but the strong concentration of market power indicates that this is rather the exception than the rule. In order to design an efficient and welfare maximizing way of regulating the market one needs a closer identification of the actual goal of the regulation. Microeconomic theory is often used for this purpose. The author discusses the alternatives of laissez-faire, nationalization or regulation for the

  8. 3D Morphing Using Strain Field Interpolation

    Institute of Scientific and Technical Information of China (English)

    Han-Bing Yan; Shi-Min Hu; Ralph R Martin

    2007-01-01

    In this paper, we present a new technique based on strain fields to carry out 3D shape morphing for applicationsin computer graphics and related areas.Strain is an important geometric quantity used in mechanics to describe the deformation of objects.We apply it in a novel way to analyze and control deformation in morphing.Using position vector fields, the strain field relating source and target shapes can be obtained.By interpolating this strain field between zero and a final desired value we can obtain the position field for intermediate shapes.This method ensures that the 3D morphing process is smooth.Locally, volumes suffer minimal distortion, and no shape jittering or wobbling happens: other methods do not necessarily have these desirable properties.We also show how to control the method so that changes of shape (in particular, size changes) vary linearly with time.

  9. Institutional Strain and Precarious Values in Meeting Future Nuclear Challenges

    Energy Technology Data Exchange (ETDEWEB)

    Bruce Matthews; Todd R. LaPorte

    1998-11-01

    This paper explores the implications of moderately expanding plutonium "pit" production capability within the strongly R&D culture of Los Alamos National Laboratory, especially in terms of the lab's current capacity or "fitness for the future" in which institutional stewardship of the nation's nuclear deterrent capability becomes a primary objective. The institutional properties needed to assure "future fitness" includes the organizational requisites highly reliable operations and sustained institutional constancy in a manner that evokes deep public trust and confidence. Estimates are made of the degree to which the key Division and most relevant Program office in this evolution already exhibits them.

  10. Diffraction tomography of strain

    OpenAIRE

    Lionheart, W R B; Withers, P. J.

    2015-01-01

    We consider whether it is possible to recover the three dimensional strain field tomographically from neutron and x-ray diffraction data for polycrystalline materials. We show that the distribution of strain transverse to a ray cannot be deduced from one diffraction pattern accumulated along that path, but that a certain moment of that data corresponds to the transverse ray transform of the strain tensor and so may be recovered by inverting that transform given sufficient data. We show that t...

  11. Strained Silicon Photonics

    Directory of Open Access Journals (Sweden)

    Ralf B. Wehrspohn

    2012-05-01

    Full Text Available A review of recent progress in the field of strained silicon photonics is presented. The application of strain to waveguide and photonic crystal structures can be used to alter the linear and nonlinear optical properties of these devices. Here, methods for the fabrication of strained devices are summarized and recent examples of linear and nonlinear optical devices are discussed. Furthermore, the relation between strain and the enhancement of the second order nonlinear susceptibility is investigated, which may enable the construction of optically active photonic devices made of silicon.

  12. Strain-engineered MOSFETs

    CERN Document Server

    Maiti, CK

    2012-01-01

    Currently strain engineering is the main technique used to enhance the performance of advanced silicon-based metal-oxide-semiconductor field-effect transistors (MOSFETs). Written from an engineering application standpoint, Strain-Engineered MOSFETs introduces promising strain techniques to fabricate strain-engineered MOSFETs and to methods to assess the applications of these techniques. The book provides the background and physical insight needed to understand new and future developments in the modeling and design of n- and p-MOSFETs at nanoscale. This book focuses on recent developments in st

  13. The efficacy of Mycoplasma gallisepticum K-strain live vaccine in broiler and layer chickens.

    Science.gov (United States)

    Ferguson-Noel, N M; Williams, S M

    2015-01-01

    The efficacy of a live Mycoplasma gallisepticum (MG) vaccine candidate (K-strain) was compared to commercially available vaccines in broiler-type chickens (Trial 1) and layer-type chickens (Trial 2). In Trial 1, three-week-old broiler-type chickens were vaccinated via aerosol with K-strain or an F-strain vaccine. The vaccinated chickens and 10 non-vaccinated controls were subsequently challenged with virulent R-strain via aerosol at six weeks post vaccination; both K-strain and F-strain vaccination resulted in significant protection from air sac and tracheal lesions, as well as R-strain colonization (P ≤ 0.05). In Trial 2, commercial layer-type chickens were vaccinated with ts-11 (via eye drop) or K-strain (via aerosol) at 12 weeks of age. At 25 weeks of age these birds were challenged with R-strain via aerosol. The ts-11 and K-strain vaccinated groups both had significantly lower air sac lesion scores and a lower prevalence of ovarian regression after challenge as compared to non-vaccinated chickens (P ≤ 0.05). K-strain vaccination also prevented significant tracheal lesions and R-strain colonization (P ≤ 0.05). K-strain shows great potential as a highly efficacious live MG vaccine in broiler and layer-type chickens for protection of the respiratory and reproductive systems as well as prevention of infection with field strains. PMID:25571953

  14. Targeting cancer with peptide aptamers

    OpenAIRE

    Seigneuric, Renaud; Gobbo, Jessica; Colas, Pierre; Garrido, Carmen

    2011-01-01

    A major endeavour in cancer chemotherapy is to develop agents that specifically target a biomolecule of interest. There are two main classes of targeting agents: small molecules and biologics. Among biologics (e.g.: antibodies), DNA, RNA but also peptide aptamers are relatively recent agents. Peptide aptamers are seldom described but represent attractive agents that can inhibit a growing panel of oncotargets including Heat Shock Proteins. Potential pitfalls and coming challenges towards succe...

  15. Proteomics Reveals that Proteins Expressed During the Early Stage of Bacillus anthracis Infection Are Potential Targets for the Development of Vaccines and Drugs

    Institute of Scientific and Technical Information of China (English)

    Chun-Ming Huang; Craig A. Elmets; De-chu C. Tang; Fuming Li; Nabiha Yusuf

    2004-01-01

    In this review, we advance a new concept in developing vaccines and/or drugs to target specific proteins expressed during the early stage of Bacillus anthracis (an thrax) infection and address existing challenges to this concept. Three proteins (immune inhibitor A, GPR-like spore protease, and alanine racemase) initially identified by proteomics in our laboratory were found to have differential expres sions during anthrax spore germination and early outgrowth. Other studies of different bacillus strains indicate that these three proteins are involved in either germination or cytotoxicity of spores, suggesting that they may serve as potential targets for the design of anti-anthrax vaccines and drugs.

  16. Targeted Learning

    CERN Document Server

    van der Laan, Mark J

    2011-01-01

    The statistics profession is at a unique point in history. The need for valid statistical tools is greater than ever; data sets are massive, often measuring hundreds of thousands of measurements for a single subject. The field is ready to move towards clear objective benchmarks under which tools can be evaluated. Targeted learning allows (1) the full generalization and utilization of cross-validation as an estimator selection tool so that the subjective choices made by humans are now made by the machine, and (2) targeting the fitting of the probability distribution of the data toward the targe

  17. Highly Strained Organophosphorus Compounds

    NARCIS (Netherlands)

    Slootweg, J.C.

    2005-01-01

    In our research on small, strained organophosphorus ring systems we became interested in the synthesis and applications of species that are even more strained than the parent phosphirane, by introducing an exocyclic double bond (methylenephosphirane), and by cyclopropyl spirofusion to the edge (e.g

  18. Selective enrichment media bias the types of Salmonella enterica strains isolated from mixed strain cultures and complex enrichment broths.

    Directory of Open Access Journals (Sweden)

    Lisa Gorski

    Full Text Available For foodborne outbreak investigations it can be difficult to isolate the relevant strain from food and/or environmental sources. If the sample is contaminated by more than one strain of the pathogen the relevant strain might be missed. In this study mixed cultures of Salmonella enterica were grown in one set of standard enrichment media to see if culture bias patterns emerged. Nineteen strains representing four serogroups and ten serotypes were compared in four-strain mixtures in Salmonella-only and in cattle fecal culture enrichment backgrounds using Salmonella enrichment media. One or more strain(s emerged as dominant in each mixture. No serotype was most fit, but strains of serogroups C2 and E were more likely to dominate enrichment culture mixtures than strains of serogroups B or C1. Different versions of Rappaport-Vassiliadis (RV medium gave different patterns of strain dominance in both Salmonella-only and fecal enrichment culture backgrounds. The fittest strains belonged to serogroups C1, C2, and E, and included strains of S. Infantis, S. Thompson S. Newport, S. 6,8:d:-, and S. Give. Strains of serogroup B, which included serotypes often seen in outbreaks such as S. Typhimurium, S. Saintpaul, and S. Schwarzengrund were less likely to emerge as dominant strains in the mixtures when using standard RV as part of the enrichment. Using a more nutrient-rich version of RV as part of the protocol led to a different pattern of strains emerging, however some were still present in very low numbers in the resulting population. These results indicate that outbreak investigations of food and/or other environmental samples should include multiple enrichment protocols to ensure isolation of target strains of Salmonella.

  19. Systems strategies for developing industrial microbial strains

    DEFF Research Database (Denmark)

    Lee, Sang Yup; Kim, Hyun Uk

    2015-01-01

    performance under industrial fermentation conditions. These challenges can be overcome by taking systems approaches through the use of state-of-the-art tools of systems biology, synthetic biology and evolutionary engineering in the context of industrial bioprocess. Major systems metabolic engineering......Industrial strain development requires system-wide engineering and optimization of cellular metabolism while considering industrially relevant fermentation and recovery processes. It can be conceptualized as several strategies, which may be implemented in an iterative fashion and in different...... orders. The key challenges have been the time-, cost- and labor-intensive processes of strain development owing to the difficulties in understanding complex interactions among the metabolic, gene regulatory and signaling networks at the cell level, which are collectively represented as overall system...

  20. Mycothiol: a promising antitubercular target.

    Science.gov (United States)

    Nilewar, S S; Kathiravan, M K

    2014-02-01

    Tuberculosis (TB) is the world's second commonest cause of death next to HIV/AIDS. The increasing emergence of multi drug resistance and the recalcitrant nature of persistent infections pose an additional challenge for the treatment of TB. Due to the development of resistance to conventional antibiotics there is a need for new therapeutic strategies to combat M. tuberculosis. One such target is Mycothiol (MSH), a major low molecular-mass thiol in mycobacteria, an important cellular anti-oxidant. MSH is present only in actinomycetes and hence is a good target. This review explores mycothiol as a potential target against tuberculosis and various research ongoing worldwide. PMID:24368170

  1. Radar automatic target recognition (ATR) and non-cooperative target recognition (NCTR)

    CERN Document Server

    Blacknell, David

    2013-01-01

    The ability to detect and locate targets by day or night, over wide areas, regardless of weather conditions has long made radar a key sensor in many military and civil applications. However, the ability to automatically and reliably distinguish different targets represents a difficult challenge. Radar Automatic Target Recognition (ATR) and Non-Cooperative Target Recognition (NCTR) captures material presented in the NATO SET-172 lecture series to provide an overview of the state-of-the-art and continuing challenges of radar target recognition. Topics covered include the problem as applied to th

  2. National Drug IQ Challenge

    Science.gov (United States)

    ... Drug & Alcohol IQ Challenge 2016 National Drug & Alcohol IQ Challenge Get Started! Correct/Total Questions: Score: Other ... accessible version of the 2016 National Drug & Alcohol IQ Challenge , [PDF, 637KB]. Download an accessible version of ...

  3. Sprains and Strains

    Science.gov (United States)

    ... people at risk for strains. Gymnastics, tennis, rowing, golf, and other sports that require extensive gripping can ... Trials and You was designed to help people learn more about clinical trials, why they matter, and ...

  4. The strained state cosmology

    CERN Document Server

    Tartaglia, Angelo

    2015-01-01

    Starting from some relevant facts concerning the behaviour of the universe over large scale and time span, the analogy between the geometric approach of General Relativ- ity and the classical description of an elastic strained material continuum is discussed. Extending the elastic deformation approach to four dimensions it is shown that the accelerated expansion of the universe is recovered. The strain field of space-time repro- duces properties similar to the ones ascribed to the dark energy currently called in to explain the accelerated expansion. The strain field in the primordial universe behaves as radiation, but asymptotically it reproduces the cosmological constant. Subjecting the theory to a number of cosmological tests confirms the soundness of the approach and gives an optimal value for the one parameter of the model, i.e. the bulk modulus of the space-time continuum. Finally various aspects of the Strained State Cosmology (SSC) are discussed and contrasted with some non-linear massive gravity theor...

  5. An Ultrasonic Strain Gauge

    OpenAIRE

    Kersemans, Mathias; Allaer, Klaas; Degrieck, Joris; Van Den Abeele, Koen; Pyl, Lincy; Zastavnik, Filip; Sol, Hugo; Van Paegem, Wim

    2014-01-01

    A method is introduced for the measurements of strain exploiting the interaction between ultrasound waves and characteristics of the insonified specimen. First, the response of obliquely incident harmonic waves to a deterministic surface roughness is utilized. Analysis of backscattered amplitudes in Bragg diffraction geometry then yields a measure for the in-plane strain field by mapping any shift in angular dependency. Secondly, the analysis of the reflection characteristics of normal incide...

  6. The tprK gene is heterogeneous among Treponema pallidum strains and has multiple alleles.

    Science.gov (United States)

    Centurion-Lara, A; Godornes, C; Castro, C; Van Voorhis, W C; Lukehart, S A

    2000-02-01

    We have previously shown that the TprK antigen of T. pallidum, Nichols strain, is predominantly expressed in treponemes obtained 10 days after infection and that the hydrophilic domain of TprK is a target of opsonic antibodies and confers significant protection against homologous challenge. The T. pallidum genome sequence reported the presence of a single copy of the tprK gene in the Nichols strain. In the present study we demonstrate size heterogeneity in the central portions of the TprK hydrophilic domains of 14 treponemal isolates. Sequence analysis of the central domains and the complete open reading frames (ORFs) of the tprK genes confirms this heterogeneity. Further, multiple tprK sequences were found in the Nichols-defined tprK locus in three isolates (Sea 81-4, Bal 7, and Bal 73-1). In contrast, only a single tprK sequence could be identified in this locus in the Nichols strain. Alignment of the DNA and deduced amino acid sequences of the whole tprK ORFs shows the presence of seven discrete variable domains flanked by highly conserved regions. We hypothesize that these heterogeneous regions may be involved in antigenic heterogeneity and, in particular, evasion of the immune response. The presence of different tprK alleles in the tprK locus strongly suggests the existence of genetically different subpopulations within treponemal isolates. PMID:10639452

  7. Changes in Macrophage Phenotype after Infection of Pigs with Haemophilus parasuis Strains with Different Levels of Virulence

    OpenAIRE

    Costa-Hurtado, Mar; Olvera, Alexandre; Martinez-Moliner, Verónica; Galofré-Milà, Nuria; Martínez, Paloma; Dominguez, Javier; Aragon, Virginia

    2013-01-01

    Haemophilus parasuis is a colonizer of healthy piglets and the etiological agent of Glässer's disease. Differences in virulence among strains of H. parasuis have been widely observed. In order to explore the host-pathogen interaction, snatch-farrowed colostrum-deprived piglets were intranasally infected with 4 strains of H. parasuis: reference virulent strain Nagasaki, reference nonvirulent strain SW114, field strain IT29205 (from a systemic lesion and virulent in a previous challenge), and f...

  8. Characterization of the Burkholderia mallei tonB Mutant and Its Potential as a Backbone Strain for Vaccine Development.

    Directory of Open Access Journals (Sweden)

    Tiffany M Mott

    Full Text Available In this study, a Burkholderia mallei tonB mutant (TMM001 deficient in iron acquisition was constructed, characterized, and evaluated for its protective properties in acute inhalational infection models of murine glanders and melioidosis.Compared to the wild-type, TMM001 exhibits slower growth kinetics, siderophore hyper-secretion and the inability to utilize heme-containing proteins as iron sources. A series of animal challenge studies showed an inverse correlation between the percentage of survival in BALB/c mice and iron-dependent TMM001 growth. Upon evaluation of TMM001 as a potential protective strain against infection, we found 100% survival following B. mallei CSM001 challenge of mice previously receiving 1.5 x 10(4 CFU of TMM001. At 21 days post-immunization, TMM001-treated animals showed significantly higher levels of B. mallei-specific IgG1, IgG2a and IgM when compared to PBS-treated controls. At 48 h post-challenge, PBS-treated controls exhibited higher levels of serum inflammatory cytokines and more severe pathological damage to target organs compared to animals receiving TMM001. In a cross-protection study of acute inhalational melioidosis with B. pseudomallei, TMM001-treated mice were significantly protected. While wild type was cleared in all B. mallei challenge studies, mice failed to clear TMM001.Although further work is needed to prevent chronic infection by TMM001 while maintaining immunogenicity, our attenuated strain demonstrates great potential as a backbone strain for future vaccine development against both glanders and melioidosis.

  9. Accelerator target

    Energy Technology Data Exchange (ETDEWEB)

    Schlyer, David J. (Bellport, NY); Ferrieri, Richard A. (Patchogue, NY); Koehler, Conrad (Miller Place, NY)

    1999-01-01

    A target includes a body having a depression in a front side for holding a sample for irradiation by a particle beam to produce a radioisotope. Cooling fins are disposed on a backside of the body opposite the depression. A foil is joined to the body front side to cover the depression and sample therein. A perforate grid is joined to the body atop the foil for supporting the foil and for transmitting the particle beam therethrough. A coolant is circulated over the fins to cool the body during the particle beam irradiation of the sample in the depression.

  10. Nano-beam electron diffraction evaluation of strain behaviour in nano-scale patterned strained silicon-on-insulator

    International Nuclear Information System (INIS)

    A major challenge for the application of strain engineering to enhance the performance of electronic devices is the quantification of strain on the nanoscale. Besides other techniques (Raman spectroscopy, X-ray diffraction) electron beam techniques allow strain analyses with a spatial resolution of a few nanometers and a reasonable strain sensitivity of 1 x 10-3 (relative to the lattice constant of silicon). In the present work, we address practical issues in the application of nano-beam electron diffraction (NBED) to probe the strain in strained silicon layers and sub-100 nm structures. The investigated specimens were prepared on biaxially tensile strained silicon-on-insulator substrates with an initial strain of ε = 0.6% or 0.8%. Results of the NBED experiments were compared to data obtained by other strain measurement techniques; amongst them the strain mapping by peak-pairs analysis of high-angle annular dark field (HAADF) images was especially considered (copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  11. MEMS Graphene Strain Sensor

    Science.gov (United States)

    Young, Clinton Wen-Chieh

    Graphene is a two dimensional honeycomb structure of sp2 hybridized carbon atoms that has possibilities in many applications due to its excellent mechanical and electrical properties. One application for Graphene is in the field of sensors. Graphene's electronic properties do not degrade when it undergoes mechanical strain which is advantageous for strain sensors. In this thesis, certain properties, such as the piezo-resistivity and flexibility, of graphene will be explored to show how they can be utilized to make a strain sensing device. Our original fabrication process of patterning graphene and the transfer process of graphene onto a flexible substrate will be discussed. The development of a stretchable and flexible graphene based rosette strain sensor will also be detailed. Developing a novel, reliable patterning process for the graphene is the first step to manufacture a stretchable graphene based sensor. The graphene was patterned using a photolithography and etching process that was developed by our research team, then it was transferred to a flexible polymer substrate with the use of a combination of soft lithography and wet etching of the Ni foil with ferric chloride solution. Graphene patterning is an essential step in fabricating reliable and sensitive sensors. With this process, graphene can be consistently patterned into different shapes and sizes. To utilize the graphene as the sensing material it also needs to be transferred onto a flexible substrate. The innovative transfer process developed by our research team consistently adheres graphene to a flexible PDMS substrate while removing the original nickel substrate. In the end, the graphene was transferred from the metal substrate to the desired flexible substrate. This process was repeated multiple times to create a stack and multilayer device. While many graphene-based strain sensors have been developed, they are uni-directional and can only measure the strain applied on the sensor in a principle

  12. 海豚链球菌感染对不同品系罗非鱼血液生化指标和肝脏HSP70 mRNA表达的影响%Studies on blood biochemical indices and expression of hepatic HSP70 mRNA of different tilapia strains artificially challenged with Streptococcus iniae

    Institute of Scientific and Technical Information of China (English)

    强俊; 杨弘; 王辉; 徐跑; 柒壮林; 何杰

    2012-01-01

    In order to establish the superiority, four different tilapia strains (GIFT tilapia, New GIFT tilapia, Egypt Nile tilapia and Red tilapia) were compared in the study. At day 100 tilapias in the treatment group were intraperitoneally injected with Streptococcus iniae suspension (2.95×108/mL) to evaluate disease resistance of four different tilapia strains against S. iniae in terms of the serum biochemical parameters and hepatic HSP70 mRNA expression before and after infection. Another set of twenty fish taken from each tank was challenged with S. iniae using the same method as above, and the cumulative mortality of 4 strains was recorded at different times post infection. The results showed that GIFT tilapia and New GIFT tilapia were more sensitive to S. iniae at 96 h after infection, cumulative mortalities were 36.67% and 38.33% respectively. Egypt Nile tilapia was less sensitive to pathogen and no death occurred during the experiment. The levels of serum cortisol (COR) and glucose (GLU) and expression levels of HSP70 mRNA in GIFT tilapia, New GIFT tilapia and Red tilapia strains were highly significant(P<0.05), and the activities of glutamic-pyruvic transaminase (ALT), glutamic-oxaloacetic transaminase (AST)and lysozyme (LSZ) also increased, while serum alkaline phosphatase (AKP), triglyceride and cholesterol levels were significantly lower than those prior to infection (P<0.05). By utilizing the energy from resolved hepatin and lipid, the synthesis of hepatic HSP70 mRNA and levels of LSZ and globulin in Egypt Nile tilapia were improved, and thus the non-specific immunity strengthened. It is suggested that in the course of tilapia breeding, effective combination of the disease resistance with growth be conducted so as to guarantee sustainable development of the tilapia industry.%以吉富罗非鱼、新吉富罗非鱼、埃及尼罗罗非鱼和红罗非鱼为研究对象,饲养100 d后,进行海豚链球菌(2.95×108 CFU/mL)感染试验,分析攻毒前后各品

  13. Target-Dependent Sentiment Classification with Long Short Term Memory

    OpenAIRE

    Tang, Duyu; Qin, Bing; Feng, Xiaocheng; Liu, Ting

    2015-01-01

    Target-dependent sentiment classification remains a challenge: modeling the semantic relatedness of a target with its context words in a sentence. Different context words have different influences on determining the sentiment polarity of a sentence towards the target. Therefore, it is desirable to integrate the connections between target word and context words when building a learning system. In this paper, we develop two target dependent long short-term memory (LSTM) models, where target inf...

  14. Spontaneous Subtle Expression Detection and Recognition based on Facial Strain

    OpenAIRE

    Liong, Sze-Teng; See, John; Phan, Raphael Chung-Wei; Oh, Yee-Hui; Ngo, Anh Cat Le; Wong, KokSheik; Tan, Su-Wei

    2016-01-01

    Optical strain is an extension of optical flow that is capable of quantifying subtle changes on faces and representing the minute facial motion intensities at the pixel level. This is computationally essential for the relatively new field of spontaneous micro-expression, where subtle expressions can be technically challenging to pinpoint. In this paper, we present a novel method for detecting and recognizing micro-expressions by utilizing facial optical strain magnitudes to construct optical ...

  15. Computational and experimental studies of strain sensitive carbon nanotube films

    OpenAIRE

    Bu, Lei

    2014-01-01

    The excellent electrical and mechanical properties of carbon nanotubes (CNTs) provide interesting opportunities to realize new types of strain gauges. However, there are still challenges for the further development of CNT film strain gauges, for instance the lack of design rules, the homogeneity, stability and reproducibility of CNT films. This thesis aims to address these issues from two sides: simulation and experiment. Monte Carlo simulations show that both the sheet resistance and gauge f...

  16. Developing a Watershed Challenge

    Science.gov (United States)

    Roman, Harry T.

    2010-01-01

    This article presents a watershed challenge that gives students an opportunity to investigate the challenge of using a watershed area as a site for development, examining the many aspects of this multifaceted problem. This design challenge could work well in a team-based format, with students taking on specific aspects of the challenges and…

  17. Andrographolide: A potent antituberculosis compound that targets Aminoglycoside 2'-N-acetyltransferase in Mycobacterium tuberculosis.

    Science.gov (United States)

    Prabu, Amudha; Hassan, Sameer; Prabuseenivasan; Shainaba, A S; Hanna, L E; Kumar, Vanaja

    2015-09-01

    Tuberculosis (TB) still remains a major challenging infectious disease. The increased rate of emergence of multi-drug resistant and extensively-drug resistant strains of the organism has further complicated the situation, resulting in an urgent need for new anti-TB drugs. Antimycobacterial activity of Andrographis paniculata was evaluated using a rapid LRP assay and the probable targets were identified by docking analysis. The methanolic extract of A. paniculata showed maximum antimycobacterial activity at 250μg/ml against all the tested strains of M. tuberculosis (H37Rv, MDR, and drug sensitive). Based on bioassay guided fractionation, andrographolide was identified as the potent molecule. With the docking analysis, both ICDH (Isocitrate Dehydrogenase) and AAC (Aminoglycoside 2'-N-acetyltransferase) were predicted as targets of andrographolide in M. tuberculosis. Molecular simulation revealed that, ICDH showed low binding affinity to andrographolide. However, for AAC, the andrographolide was observed to be well within the active site after 10ns of molecular simulation. This suggests that ACC (PDB ID 1M4I) could be the probable target for andrographolide. PMID:26245695

  18. Next-Generation Bacillus anthracis Live Attenuated Spore Vaccine Based on the htrA(-) (High Temperature Requirement A) Sterne Strain.

    Science.gov (United States)

    Chitlaru, Theodor; Israeli, Ma'ayan; Bar-Haim, Erez; Elia, Uri; Rotem, Shahar; Ehrlich, Sharon; Cohen, Ofer; Shafferman, Avigdor

    2016-01-01

    Anthrax is a lethal disease caused by the gram-positive spore-producing bacterium Bacillus anthracis. Live attenuated vaccines, such as the nonencapsulated Sterne strain, do not meet the safety standards mandated for human use in the Western world and are approved for veterinary purposes only. Here we demonstrate that disrupting the htrA gene, encoding the chaperone/protease HtrA (High Temperature Requirement A), in the virulent Bacillus anthracis Vollum strain results in significant virulence attenuation in guinea pigs, rabbits and mice, underlying the universality of the attenuated phenotype associated with htrA knockout. Accordingly, htrA disruption was implemented for the development of a Sterne-derived safe live vaccine compatible with human use. The novel B. anthracis SterneΔhtrA strain secretes functional anthrax toxins but is 10-10(4)-fold less virulent than the Sterne vaccine strain depending on animal model (mice, guinea pigs, or rabbits). In spite of this attenuation, double or even single immunization with SterneΔhtrA spores elicits immune responses which target toxaemia and bacteremia resulting in protection from subcutaneous or respiratory lethal challenge with a virulent strain in guinea pigs and rabbits. The efficacy of the immune-protective response in guinea pigs was maintained for at least 50 weeks after a single immunization. PMID:26732659

  19. Targeted therapy: tailoring cancer treatment

    Institute of Scientific and Technical Information of China (English)

    Min Yan; Quentin Qiang Liu

    2013-01-01

    Targeted therapies include small-molecule inhibitors and monoclonal antibodies,have made treatment more tumor-specific and less toxic,and have opened new possibilities for tailoring cancer treatment.Nevertheless,there remain several challenges to targeted therapies,including molecular identification,drug resistance,and exploring reliable biomarkers.Here,we present several selected signaling pathways and molecular targets involved in human cancers including Aurora kinases,PI3K/mTOR signaling,FOXO-FOXM1 axis,and MDM2/MDM4-p53 interaction.Understanding the molecular mechanisms for tumorigenesis and development of drug resistance will provide new insights into drug discovery and design of therapeutic strategies for targeted therapies.

  20. Parallel Microcracks-based Ultrasensitive and Highly Stretchable Strain Sensors.

    Science.gov (United States)

    Amjadi, Morteza; Turan, Mehmet; Clementson, Cameron P; Sitti, Metin

    2016-03-01

    There is an increasing demand for flexible, skin-attachable, and wearable strain sensors due to their various potential applications. However, achieving strain sensors with both high sensitivity and high stretchability is still a grand challenge. Here, we propose highly sensitive and stretchable strain sensors based on the reversible microcrack formation in composite thin films. Controllable parallel microcracks are generated in graphite thin films coated on elastomer films. Sensors made of graphite thin films with short microcracks possess high gauge factors (maximum value of 522.6) and stretchability (ε ≥ 50%), whereas sensors with long microcracks show ultrahigh sensitivity (maximum value of 11,344) with limited stretchability (ε ≤ 50%). We demonstrate the high performance strain sensing of our sensors in both small and large strain sensing applications such as human physiological activity recognition, human body large motion capturing, vibration detection, pressure sensing, and soft robotics. PMID:26842553

  1. Longitudinal misalignment based strain sensor

    OpenAIRE

    Andrews, Jeffrey Pratt

    1989-01-01

    A practical fiber optic strain sensor has been developed to measure strains in the range of 0.0 to 2.0 percent strain with a resolution ranging between 10 and 100 microstrain depending on sensor design choices. This intensity based sensor measures strain by monitoring strain induced longitudinal misalignment in a novel fiber interconnection. This interconnection is created by aligning fibers within a segment of hollow core fiber. Related splice loss mechanisms are investigated ...

  2. ConStrains identifies microbial strains in metagenomic datasets.

    Science.gov (United States)

    Luo, Chengwei; Knight, Rob; Siljander, Heli; Knip, Mikael; Xavier, Ramnik J; Gevers, Dirk

    2015-10-01

    An important fraction of microbial diversity is harbored in strain individuality, so identification of conspecific bacterial strains is imperative for improved understanding of microbial community functions. Limitations in bioinformatics and sequencing technologies have to date precluded strain identification owing to difficulties in phasing short reads to faithfully recover the original strain-level genotypes, which have highly similar sequences. We present ConStrains, an open-source algorithm that identifies conspecific strains from metagenomic sequence data and reconstructs the phylogeny of these strains in microbial communities. The algorithm uses single-nucleotide polymorphism (SNP) patterns in a set of universal genes to infer within-species structures that represent strains. Applying ConStrains to simulated and host-derived datasets provides insights into microbial community dynamics. PMID:26344404

  3. Nine challenges for deterministic epidemic models

    Directory of Open Access Journals (Sweden)

    Mick Roberts

    2015-03-01

    Full Text Available Deterministic models have a long history of being applied to the study of infectious disease epidemiology. We highlight and discuss nine challenges in this area. The first two concern the endemic equilibrium and its stability. We indicate the need for models that describe multi-strain infections, infections with time-varying infectivity, and those where superinfection is possible. We then consider the need for advances in spatial epidemic models, and draw attention to the lack of models that explore the relationship between communicable and non-communicable diseases. The final two challenges concern the uses and limitations of deterministic models as approximations to stochastic systems.

  4. Nine challenges for deterministic epidemic models

    DEFF Research Database (Denmark)

    Roberts, Mick G; Andreasen, Viggo; Lloyd, Alun;

    2015-01-01

    Deterministic models have a long history of being applied to the study of infectious disease epidemiology. We highlight and discuss nine challenges in this area. The first two concern the endemic equilibrium and its stability. We indicate the need for models that describe multi-strain infections......, infections with time-varying infectivity, and those where superinfection is possible. We then consider the need for advances in spatial epidemic models, and draw attention to the lack of models that explore the relationship between communicable and non-communicable diseases. The final two challenges concern...

  5. Open Platforms: New Challenges for Software Engineering

    OpenAIRE

    Balland, Emilie; Consel, Charles

    2010-01-01

    Recently, platforms running third-party applications have become very popular, in particular due to the explosion of the smartphone market. These open platforms propose a rich stream of applications, targeting general-purpose as well as customized user needs. Developing applications for such target platforms introduces new requirements and raises new challenges. This paper identifies key requirements for designing open platforms. After an overview of the existing approaches, we identify the c...

  6. Prior Inoculation with Type B Strains of Francisella tularensis Provides Partial Protection against Virulent Type A Strains in Cottontail Rabbits.

    Directory of Open Access Journals (Sweden)

    Vienna R Brown

    Full Text Available Francisella tularensis is a highly virulent bacterium that is capable of causing severe disease (tularemia in a wide range of species. This organism is characterized into two distinct subspecies: tularensis (type A and holarctica (type B which vary in several crucial ways, with some type A strains having been found to be considerably more virulent in humans and laboratory animals. Cottontail rabbits have been widely implicated as a reservoir species for this subspecies; however, experimental inoculation in our laboratory revealed type A organisms to be highly virulent, resulting in 100% mortality following challenge with 50-100 organisms. Inoculation of cottontail rabbits with the same number of organisms from type B strains of bacteria was found to be rarely lethal and to result in a robust humoral immune response. The objective of this study was to characterize the protection afforded by a prior challenge with type B strains against a later inoculation with a type A strain in North American cottontail rabbits (Sylvilagus spp. Previous infection with a type B strain of organism was found to lengthen survival time and in some cases prevent death following inoculation with a type A2 strain of F. tularensis. In contrast, inoculation of a type A1b strain was uniformly lethal in cottontail rabbits irrespective of a prior type B inoculation. These findings provide important insight about the role cottontail rabbits may play in environmental maintenance and transmission of this organism.

  7. The strained state cosmology

    Science.gov (United States)

    Tartaglia, Angelo

    2016-01-01

    Starting from some relevant facts concerning the behavior of the universe over large scale and time span, the analogy between the geometric approach of General Relativity and the classical description of an elastic strained material continuum is discussed. Extending the elastic deformation approach to four dimensions it is shown that the accelerated expansion of the universe is recovered. The strain field of space-time reproduces properties similar to the ones ascribed to the dark energy currently called in to explain the accelerated expansion. The strain field in the primordial universe behaves as radiation, but asymptotically it reproduces the cosmological constant. Subjecting the theory to a number of cosmological tests confirms the soundness of the approach and gives an optimal value for the one parameter of the model, i.e. the bulk modulus of the space-time continuum. Finally various aspects of the Strained State Cosmology (SSC) are discussed and contrasted with some non-linear massive gravity theories. The possible role of structure topological defects is also mentioned. The conclusion is that SSC is at least as good as the ΛCDM standard cosmology, giving a more intuitive interpretation of the physical nature of the phenomena.

  8. 5-Fluorouracil-resistant strain of Methanobacterium thermoautortrophicum

    International Nuclear Information System (INIS)

    Growth of Methanobacterium thermoautotrophicum Marburg is inhibited by the pyrimidine, 5-fluorouracil (FU). It was shown previously that methanogenesis is not inhibited to the same extent as growth. A spontaneously occurring FU-resistant strain (RTAE-1) was isolated from a culture of strain Marburg. The growth of both strains was inhibited by 5-fluorodeoxyuridine but not 5-fluorocytosine, and the wild type was more susceptible to inhibition by 5-azauracil and 6-azauracil than was strain RTAE-1. The cellular targets for the pyrimidine analogs are not known. When the accumulation of 14C-labeled uracil or FU by the two strains was compared, the wilt type took up 15-fold more radiolabel per cell than did the FU-resistant strain. In the wild type, radiolabel from uracil was incorporated into the soluble pool, RNA, and DNA. The metabolism of uracil appeared to involve a uracil phosphoribosyltransferase activity. Strain Marburg extracts contained this enzyme, whereas FU-resistant strain RTAE-1 extracts had less than 1/10 as much activity. Although it is possible that a change in permeability to the compounds plays a role in the stable resistance of strain RTAE-1, the fact that it lacks the ability to metabolize pyrimidines to nucleotides is sufficient to account for its phenotype

  9. Antimicrobial resistance among Brazilian Corynebacterium diphtheriae strains

    Directory of Open Access Journals (Sweden)

    Gabriela Andrade Pereira

    2008-08-01

    Full Text Available The increasing problems with multidrug resistance in relation to Corynebacterium, including C. diphtheriae, are examples of challenges confronting many countries. For this reason, Brazilian C. diphtheriae strains were evaluated by the E-Test for their susceptibility to nine antibacterial drugs used in therapy. Resistance (MIC < 0.002; 0.38 µg/ml to penicillin G was found in 14.8% of the strains tested. Although erythromycin (MIC90 0.75 µg/ml and azithromycin (MIC90 0.064 µg/ml were active against C. diphtheriae in this study, 4.2% of the strains showed decreased susceptibility (MIC 1.0 µg/ml to erythromycin. Multiple resistance profiles were determined by the disk diffusion method using 31 antibiotics. Most C. diphtheriae strains (95.74% showed resistance to mupirocin, aztreonam, ceftazidime, and/or oxacillin, ampicillin, penicillin, tetracycline, clindamycin, lincomycin, and erythromycin. This study presents the antimicrobial susceptibility profiles of Brazilian C. diphtheriae isolates. The data are of value to practitioners, and suggest that some concern exists regarding the use of penicillin.

  10. 78 FR 49296 - Centennial Challenges 2014 Sample Return Robot Challenge

    Science.gov (United States)

    2013-08-13

    ... SPACE ADMINISTRATION Centennial Challenges 2014 Sample Return Robot Challenge AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Notice of Centennial Challenges 2014 Sample Return Robot... Robot Challenge is scheduled and teams that wish to compete may register. Centennial Challenges is...

  11. LIFE Target Fabrication Research Plan Sept 2008

    Energy Technology Data Exchange (ETDEWEB)

    Miles, R; Biener, J; Kucheyev, S; Montesanti, R; Satcher, J; Spadaccini, C; Rose, K; Wang, M; Hamza, A; Alexander, N; Brown, L; Hund, J; Petzoldt, R; Sweet, W; Goodin, D

    2008-11-10

    The target-system for the baseline LIFE fast-ignition target was analyzed to establish a preliminary estimate for the costs and complexities involved in demonstrating the technologies needed to build a prototype LIFE plant. The baseline fast-ignition target upon which this analysis was developed is shown in Figure 1.0-1 below. The LIFE target-system incorporates requirements for low-cost, high throughput manufacture, high-speed, high accuracy injection of the target into the chamber, production of sufficient energy from implosion and recovery and recycle of the imploded target material residue. None of these functions has been demonstrated to date. Existing target fabrication techniques which lead to current 'hot spot' target costs of {approx}$100,000 per target and at a production rate of 2/day are unacceptable for the LIFE program. Fabrication techniques normally used for low-cost, low accuracy consumer products such as toys must be adapted to the high-accuracy LIFE target. This will be challenge. A research program resulting is the demonstration of the target-cycle technologies needed for a prototype LIFE reactor is expected to cost {approx}$51M over the course of 5 years. The effort will result in targets which will cost an estimated $0.23/target at a rep-rate of 20 Hz or about 1.73M targets/day.

  12. Risk factors for fecal colonization with multiple distinct strains of Escherichia coli among long-term care facility residents.

    Science.gov (United States)

    Lautenbach, Ebbing; Tolomeo, Pam; Black, Nicole; Maslow, Joel N

    2009-05-01

    Of 49 long-term care facility residents, 21 (43%) were colonized with 2 or more distinct strains of Escherichia coli. There were no significant risk factors for colonization with multiple strains of E. coli. These results suggest that future efforts to efficiently identify the diversity of colonizing strains will be challenging. PMID:19292660

  13. Risk Factors for Fecal Colonization with Multiple Distinct Strains of Escherichia coli Among Long-Term Care Facility Residents

    OpenAIRE

    Lautenbach, Ebbing; Tolomeo, Pam; Black, Nicole; Maslow, Joel N.

    2009-01-01

    Of 49 long-term care facility residents, 21 (43%) were colonized with two or more distinct strains of Escherichia coli. There were no significant risk factors for colonization with multiple strains of E. coli. These results suggest future efforts to efficiently identify diversity of colonizing strains will be challenging.

  14. Targeting JAK kinase in solid tumors: emerging opportunities and challenges.

    Science.gov (United States)

    Buchert, M; Burns, C J; Ernst, M

    2016-02-25

    Various human malignancies are characterized by excessive activation of the Janus family of cytoplasmic tyrosine kinases (JAK) and their associated transcription factors STAT3 and STAT5. In the majority of solid tumors, this occurs in response to increased abundance of inflammatory cytokines in the tumor microenvironment prominently produced by infiltrating innate immune cells. Many of these cytokines share common receptor subunits and belong to the interleukin (IL)-6/IL-11, IL-10/IL-22 and IL-12/IL-23 families. Therapeutic inhibition of the JAK/STAT3 pathway potentially offers considerable benefit owing to the capacity of JAK/STAT3 signaling to promote cancer hallmarks in the tumor and its environment, including proliferation, survival, angiogenesis, tumor metabolism while suppressing antitumor immunity. This is further emphasized by the current successful clinical applications of JAK-specific small molecule inhibitors for the treatment of inflammatory disorders and hematopoietic malignancies. Here we review current preclinical applications for JAK inhibitors for the treatment of solid cancers in mice, with a focus on the most common malignancies emanating from oncogenic transformation of the epithelial mucosa in the stomach and colon. Emerging data with small molecule JAK-specific adenosine triphosphate-binding analogs corroborate genetic findings and suggest that interference with the JAK/STAT3 pathway may suppress the growth of the most common forms of sporadic colon cancers that arise from mutations of the APC tumor suppressor gene. Likewise inhibition of cytokine-dependent activation of the JAK/STAT3 pathway may also afford orthogonal treatment opportunities for other oncogene-addicted cancer cells that have gained drug resistance. PMID:25982279

  15. Tapping Stem Cells to Target AMD: Challenges and Prospects

    Directory of Open Access Journals (Sweden)

    Caroline Brandl

    2015-01-01

    Full Text Available Human pluripotent stem cells (hPSCs are increasingly gaining attention in biomedicine as valuable resources to establish patient-derived cell culture models of the cell type known to express the primary pathology. The idea of “a patient in a dish” aims at basic, but also clinical, applications with the promise to mimic individual genetic and metabolic complexities barely reflected in current invertebrate or vertebrate animal model systems. This may particularly be true for the inherited and complex diseases of the retina, as this tissue has anatomical and physiological aspects unique to the human eye. For example, the complex age-related macular degeneration (AMD, the leading cause of blindness in Western societies, can be attributed to a large number of genetic and individual factors with so far unclear modes of mutual interaction. Here, we review the current status and future prospects of utilizing hPSCs, specifically induced pluripotent stem cells (iPSCs, in basic and clinical AMD research, but also in assessing potential treatment options. We provide an outline of concepts for disease modelling and summarize ongoing and projected clinical trials for stem cell-based therapy in late-stage AMD.

  16. Vestibular migraine: diagnosis challenges and need for targeted treatment.

    Science.gov (United States)

    Barbosa, Felipe; Villa, Thaís Rodrigues

    2016-05-01

    Approximately 1% of the general population suffers from vestibular migraine. Despite the recently published diagnostic criteria, it is still underdiagnosed condition. The exact neural mechanisms of vestibular migraine are still unclear, but the variability of symptoms and clinical findings both during and between attacks suggests an important interaction between trigeminal and vestibular systems. Vestibular migraine often begins several years after typical migraine and has a variable clinical presentation. In vestibular migraine patients, the neurological and neurotological examination is mostly normal and the diagnosis will be based in the patient clinical history. Treatment trials that specialize on vestibular migraine are scarce and therapeutic recommendations are based on migraine guidelines. Controlled studies on the efficacy of pharmacologic interventions in the treatment of vestibular migraine should be performed. PMID:27191239

  17. Challenging nanoparticles: a target of personalized adhesion prevention strategy

    OpenAIRE

    Mynbaev OA; Eliseeva MY; Malvasi A; Tinelli A

    2014-01-01

    Ospan A Mynbaev,1–4 Marina Yu Eliseeva,2 Antonio Malvasi,5 Andrea Tinelli6 1International Translational Medicine and Biomodeling Research Team, MIPT Center for Human Physiology, Department of Applied Mathematics, Moscow Institute of Physics and Technology (State University), Dolgoprudny, Moscow Region, Russia; 2Department of Obstetrics, Gynecology and Reproductive Medicine, Peoples’ Friendship University of Russia, Moscow, Russia; 3Laboratory of Pilot Projects, Moscow State Unive...

  18. Challenging nanoparticles: a target of personalized adhesion prevention strategy

    OpenAIRE

    Mynbaev, Ospan

    2014-01-01

    Ospan A Mynbaev,1–4 Marina Yu Eliseeva,2 Antonio Malvasi,5 Andrea Tinelli6 1International Translational Medicine and Biomodeling Research Team, MIPT Center for Human Physiology, Department of Applied Mathematics, Moscow Institute of Physics and Technology (State University), Dolgoprudny, Moscow Region, Russia; 2Department of Obstetrics, Gynecology and Reproductive Medicine, Peoples’ Friendship University of Russia, Moscow, Russia; 3Laboratory of Pilot Projects, Moscow Sta...

  19. Challenging nanoparticles: a target of personalized adhesion prevention strategy

    Directory of Open Access Journals (Sweden)

    Mynbaev OA

    2014-07-01

    Full Text Available Ospan A Mynbaev,1–4 Marina Yu Eliseeva,2 Antonio Malvasi,5 Andrea Tinelli6 1International Translational Medicine and Biomodeling Research Team, MIPT Center for Human Physiology, Department of Applied Mathematics, Moscow Institute of Physics and Technology (State University, Dolgoprudny, Moscow Region, Russia; 2Department of Obstetrics, Gynecology and Reproductive Medicine, Peoples’ Friendship University of Russia, Moscow, Russia; 3Laboratory of Pilot Projects, Moscow State University of Medicine and Dentistry, Moscow, Russia; 4The New European Surgical Academy, Berlin, Germany; 5Department of Obstetrics and Gynecology, Santa Maria Hospital, Bari, Italy; 6Department of Obstetrics and Gynaecology, Division of Experimental Endoscopic Surgery, Imaging, Minimally Invasive Therapy and Technology, Vito Fazzi Hospital, Lecce, ItalyWith great interest we have read an article by Wu et al1 recently published in the International Journal of Nanomedicine aimed to estimate cytotoxicity, toxicity, and histopathological changes, as well as the postsurgical antiadhesion potential of biodegradable and thermosensitive micelles by combining in vitro and in vivo models.Our congratulations to Wu et al1 for their new, precisely designed, and promising study of nanoparticles used in the prevention of postsurgical adhesions. Even more so when we know that in most clinical studies the adhesion prevention adjuvants have failed. Taking into account medical and financial problems associated with postsurgical adhesions worldwide in the health care system, new developments in this area are welcomed and call for further investigation.View orginal paper by Wu et al

  20. Challenges and Approaches for Mosquito Targeted Malaria Control

    OpenAIRE

    Ramirez, José L.; Garver, Lindsey S.; Dimopoulos, George

    2009-01-01

    Malaria is one of today’s most serious diseases with an enormous socioeconomic impact. While anti-malarial drugs have existed for some time and vaccines development may be underway, the most successful malaria eradication programs have thus far relied on attacking the mosquito vector that spreads the disease causing agent Plasmodium. Here we will review past, current and future perspectives of malaria vector control strategies and how these approaches have taken a promising turn thanks recent...

  1. Challenges of Parenting Multiples

    Science.gov (United States)

    ... the American Society for Reproductive Medicine Challenges of Parenting Multiples There are many psychological, social, and economic ... the unique challenges and rewards that come from parenting multiples. For more information on the medical aspects ...

  2. Overcoming Breastfeeding Challenges

    Medline Plus

    Full Text Available ... on Women's Health Skip Navigation Skip top navigation Home A-Z Health Topics ePublications News About Us ... Only Natural email updates. Enter email address Submit Home > It's Only Natural > Overcoming challenges Overcoming breastfeeding challenges ...

  3. Overcoming Breastfeeding Challenges

    Medline Plus

    Full Text Available ... size | Print | Skip left navigation It's Only Natural Planning ahead Overcoming challenges Overcoming breastfeeding challenges Dealing with lack of family support Is my baby getting enough milk? Breastfeeding ...

  4. Overcoming Breastfeeding Challenges

    Medline Plus

    Full Text Available A project of the U.S. Department of Health and Human Services Office on Women's Health Skip Navigation ... challenges Overcoming breastfeeding challenges Dealing with lack of family support Is my baby getting enough ...

  5. The Backpack Design Challenge

    Science.gov (United States)

    Roman, Harry T.

    2010-01-01

    Something as simple as carrying books to school can be an interesting design challenge for students. It's an old problem that gets reinvented from time to time. In this article, the author discusses a backpack design challenge in which teachers work with students to design another way to carry books to school. The challenge started by trying to…

  6. Immunogenic and antigenic activity of an experimental oral rabies vaccine prepared from the strain Vnukovo-32/107.

    Science.gov (United States)

    Svrcek, S; Durove, A; Ondrejka, R; Závadová, J; Süliová, J; Benísek, Z; Vrtiak, O J; Feketeová, J; Mad'ar, M

    1995-03-01

    The immunogenic and antigenic activity of an experimental live oral rabies vaccine prepared from the strain Vnukovo-32/107 was evaluated on the basis of results obtained in 3 sets of experiments. These were carried out as model experiments on white mice, then on target animals--red foxes (Vulpes vulpes) and a related species--farm-bred polar foxes (Alopex lagopus). For quantitative determination of the immunogenic activity of the orally or subcutaneously administered rabies vaccines in model experiments on mice a method was used that had been developed in our laboratory. Antibodies were detected and quantified by an ELISA kit that had also been developed in our lab. Tenacity of the experimental vaccine (infectious tissue culture medium after yolk addition) was verified at different temperatures; the effects of storage temperature upon virus titre and immunogenic activity were investigated. An important part of the experiments--evaluation of the antigenic and immunogenic activity of the live vaccine at oral vaccination (vaccination baits, conditions simulating field vaccination) was carried out in foxes. The immunogenic activity (challenge experiments with a street virus on day 180 and 360 after vaccination) was evaluated in common foxes (Vulpes vulpes). The results document a high immunogenic and antigenic activity of the experimental live oral rabies vaccine. The strain Vnukovo-32/107 is suitable for the industrial manufacturing of vaccination baits. In the target species--common foxes challenged on day 180 after primovaccination an 83% protection was observed. Challenge on day 180 after revaccination (or day 360 after primovaccination), the orally immunized foxes proved to be 100% protected. For parallel evaluation of the immunogenic activity of an oral vaccine and for antibody titration it is recommended to employ the quantitative mice test and an ELISA technique, respectively. PMID:7762124

  7. Energy transition - economic challenge, climate challenge, industrial challenge

    International Nuclear Information System (INIS)

    This document highlights and discusses the different economic, climate and industrial challenges, identifies and discusses the different objectives and main results for a successful energy transition respectively in its relationships with the energy mix (the result is to divide emissions by a factor 4), with governance (the result should be a balanced distribution of energy governance), with energy consumption

  8. Printing of stretchable silk membranes for strain measurements.

    Science.gov (United States)

    Ling, Shengjie; Zhang, Qiang; Kaplan, David L; Omenetto, Fiorenzo; Buehler, Markus J; Qin, Zhao

    2016-07-01

    Quantifying the deformation of biological tissues under mechanical loading is crucial to understand its biomechanical response in physiological conditions and important for designing materials and treatments for biomedical applications. However, strain measurements for biological tissues subjected to large deformations and humid environments are challenging for conventional methods due to several limitations such as strain range, boundary conditions, surface bonding and biocompatibility. Here we propose the use of silk solutions and printing to synthesize prototype strain gauges for large strain measurements in biological tissues. The study shows that silk-based strain gauges can be stretched up to 1300% without failure, which is more than two orders of magnitude larger than conventional strain gauges, and the mechanics can be tuned by adjusting ion content. We demonstrate that the printing approach can accurately provide well bonded fluorescent features on the silk membranes using designs which can accurately measure strain in the membrane. The results show that these new strain gauges measure large deformations in the materials by eliminating the effects of sliding from the boundaries, making the measurements more accurate than direct outputs from tensile machines. PMID:27241909

  9. Target Housing Material Options

    Energy Technology Data Exchange (ETDEWEB)

    Woloshun, Keith Albert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-02-11

    With gas cooling, heat transfer coefficients are low compared to water. The benefit of gas from a heat transfer point of view is that there is really no upper temperature limit for the coolant, as compared to water, which is limited ultimately by the critical point, and in practice the critical heat flux. In our case with parallel flow channels, water is limited to even lower operating limits by nucleate boiling. So gas can get as hot as the containment material will allow, but to get the density and heat transfer up to something reasonable, we must also increase pressure, thus increasing stress on the containment, namely the front and back faces. We are designing to ASME BPVC, which, for most materials allows a maximum stress of UTS/3. So we want the highest possible UTS. For reference, the front face stress in the 12 mm target at 300 psi was about 90 MPa. The inconel 718 allowable stress at 900°C is 1/3 of 517 or 172 MPa. So we are in a very safe place, but the uTS is dropping rapidly with temperature above 900°C. As we increase target diameter, the challenge will be to keep the stress down. We are probably looking at keeping the allowable at or above the present value, and at as high a temperature as possible.

  10. Accuracy of visual scoring and semi-quantification of ultrasound strain elastography--a phantom study.

    Directory of Open Access Journals (Sweden)

    Jonathan Frederik Carlsen

    Full Text Available PURPOSE: The aim of this study was to evaluate the performance of strain elastography in an elasticity phantom and to assess which factors influenced visual scoring, strain histograms and strain ratios. Furthermore this study aimed to evaluate the effect of observer experience on visual scorings. MATERIALS AND METHODS: Two operators examined 20 targets of various stiffness and size (16.7 to 2.5 mm in an elasticity phantom at a depth of 3.5 cm with a 5-18 MHz transducer. Two pre-settings were used yielding 80 scans. Eight evaluators, four experienced, four inexperienced, performed visual scorings. Cut-offs for semi-quantitative methods were established for prediction of target stiffness. Data was pooled in two categories allowing calculations of sensitivity and specificity. Statistical tests chi-square test and linear regression as relevant. RESULTS: Strain ratios and strain histograms were superior to visual scorings of both experienced and inexperienced observers (p = 0.025, strain histograms vs. experienced observers, p<0.001, strain histograms vs. inexperienced observers, p = 0.044 strain ratios vs. experienced observers and p = 0.002 strain ratios vs. inexperienced observers. No significant difference in predicting target stiffness between strain ratios and strain histograms (p = 0.83 nor between experienced and inexperienced observers (p = 0.054 was shown when using four categories. When pooling data in two groups (80 kPa/45 kPa vs. 14/8 kPa the difference between the observers became significant (p<0.001. Target size had a significant influence on strain ratios measurements (p = 0.017 and on visual scorings (p<0.001 but not on the strain histograms(p = 0.358. Observer experience had significant effect on visual scorings(p = 0.003. CONCLUSION: Strain ratios and strain histograms are superior to visual scoring in assessing target stiffness in a phantom. Target size had a significant impact on strain ratios and

  11. Novel strained superjunction VDMOS

    Science.gov (United States)

    Naugarhiya, Alok; Dubey, Shashank; Kondekar, Pravin N.

    2015-09-01

    In this paper, we have proposed novel strained superjunction (s-SJ) vertical double diffused MOS (VDMOS). Through channel engineering, we have introduced strain effects in s-SJ device using thin separate p-type silicon-germanium (p-SiGe) layer over silicon p-pillar. Further, we have designed process flow for the possible fabrication of s-SJ VDMOS. The proposed s-SJ devices fitted with less input capacitance (Cin) and 1.2∼3 times higher output current density than conventional SJ VDMOS. Therefore, 40% less gate charge (Qg) is required to turn-on the s-SJ VDMOS and Ron A is optimized in between 12% and 46%.

  12. Strains in general relativity

    International Nuclear Information System (INIS)

    The definition of relative accelerations and strains among a set of comoving particles is studied in connection with the geometric properties of the frame adapted to a 'fiducial observer'. We find that a relativistically complete and correct definition of strains must take into account the transport law of the chosen spatial triad along the observer's congruence. We use special congruences of (accelerated) test particles in some familiar spacetimes to elucidate such a point. The celebrated idea of Szekeres' compass of inertia, arising when studying geodesic deviation among a set of free-falling particles, is here generalized to the case of accelerated particles. In doing so we have naturally contributed to the theory of relativistic gravity gradiometer. Moreover, our analysis was made in an observer-dependent form, a fact that would be very useful when thinking about general relativistic tests on space stations orbiting compact objects like black holes and also in other interesting gravitational situations

  13. Strains in General Relativity

    CERN Document Server

    Bini, Donato; Geralico, Andrea

    2014-01-01

    The definition of relative accelerations and strains among a set of comoving particles is studied in connection with the geometric properties of the frame adapted to a "fiducial observer." We find that a relativistically complete and correct definition of strains must take into account the transport law of the chosen spatial triad along the observer's congruence. We use special congruences of (accelerated) test particles in some familiar spacetimes to elucidate such a point. The celebrated idea of Szekeres' compass of inertia, arising when studying geodesic deviation among a set of free-falling particles, is here generalized to the case of accelerated particles. In doing so we have naturally contributed to the theory of relativistic gravity gradiometer. Moreover, our analysis was made in an observer-dependent form, a fact that would be very useful when thinking about general relativistic tests on space stations orbiting compact objects like black holes and also in other interesting gravitational situations.

  14. Characterization of recombinant B. abortus strain RB51SOD towards understanding the uncorrelated innate and adaptive immune responses induced by RB51SOD compared to its parent vaccine strain RB51

    Directory of Open Access Journals (Sweden)

    Jianguo eZhu

    2011-11-01

    Full Text Available Brucella abortus is a Gram-negative, facultative intracellular pathogen for several mammals, including humans. Live attenuated B. abortus strain RB51 is currently the official vaccine used against bovine brucellosis in the United States and several other countries. Overexpression of protective B. abortus antigen Cu/Zn superoxide dismutase (SOD in a recombinant strain of RB51 (strain RB51SOD significantly increases its vaccine efficacy against virulent B. abortus challenge in a mouse model. An attempt has been made to better understand the mechanism of the enhanced protective immunity of RB51SOD compared to its parent strain RB51. We previously reported that RB51SOD stimulated enhanced Th1 immune response. In this study, we further found that T effector cells derived from RB51SOD-immunized mice exhibited significantly higher cytotoxic T lymphocyte (CTL activity than T effector cells derived from RB51-immunized mice against virulent B. abortus-infected target cells. Meanwhile, the macrophage responses to these two strains were also studied. Compared to RB51, RB51SOD cells had a lower survival rate in macrophages and induced lower levels of macrophage apoptosis and necrosis. The decreased survival of RB51SOD cells correlates with the higher sensitivity of RB51SOD, compared to RB51, to the bactericidal action of either Polymyxin B or sodium dodecyl sulfate (SDS. Furthermore, a physical damage to the outer membrane of RB51SOD was observed by electron microscopy. Possibly due to the physical damage, overexpressed Cu/Zn SOD in RB51SOD was found to be released into the bacterial cell culture medium. Therefore, the stronger adaptive immunity induced by RB51SOD did not correlate with the low level of innate immunity induced by RB51SOD compared to RB51. This unique and apparently contradictory profile is likely associated with the differences in outer membrane integrity and Cu/Zn SOD release.

  15. Software Engineering Challenges of Migration Projects

    Directory of Open Access Journals (Sweden)

    S.Geetha

    2012-03-01

    Full Text Available Organisations often face the challenges of migration from legacy systems to new target systems. Such migration efforts represent a complex engineering problem. This paper describes migration planning, identifies influencing factors, outlines a set of migration planning activities and offers a set of guidelines for the migration planning

  16. Software Engineering Challenges of Migration Projects

    OpenAIRE

    Geetha, S.; Dr.Alagaramy

    2012-01-01

    Organisations often face the challenges of migration from legacy systems to new target systems. Such migration efforts represent a complex engineering problem. This paper describes migration planning, identifies influencing factors, outlines a set of migration planning activities and offers a set of guidelines for the migration planning

  17. Geodetic surveying of strains

    Energy Technology Data Exchange (ETDEWEB)

    Meixner, H.

    1980-11-01

    This article evaluates methods and apparatus used in the German Democratic Republic to assess vertical and horizontal deformations and strains caused by coal mining and mining of other deposits. Each of the methods is characterized; type of measuring apparatus and its accuracy is given. The following conventional methods of surveying are characterized: (I.) vertical strains: measurement with hydrostatic tube balance (apparatus produced by the Praezisionsmechanik Freiberg, with accuracy of 0.01 mm), trigonometric levelling (error up to 10 mm), geometric levelling (NI 007 and NI 008 apparatus produced by Carl Zeiss JENA), and direct height measuring; (II.) horizontal strains: direct surveying with accuracy higher than 5 mm/50 m, indirect surveying (theodolite THEO 010 A produced by the Carl Zeiss JENA), and alignment method (using apparatus produced by Praezisionsmechanik, Freiberg). Advanced surveying methods are also discussed: electro-optical method (using EOK 2000 range finder produced by Carl Zeiss JENA, with average error ranging from 5 mm to 10 mm), laser method (LF-1 and LFG-1 lasers produced by Carl Zeiss JENA), measuring gyroscope used to measure contorsion (MRK 2 gyroscope produced by the Praezisionsmechanik, Freiberg); photogrammetry: stereophotogrammetry and so-called parallel photogrammetry. (15 refs.) (In Polish)

  18. Capsule Production in Bacillus cereus Strains Associated with Severe Pneumonia

    OpenAIRE

    Sue, David; Hoffmaster, Alex R.; Popovic, Tanja; Wilkins, Patricia P.

    2006-01-01

    We identified three encapsulated Bacillus cereus strains, isolated from patients with severe pneumonia, in a collection of B. cereus isolates associated with human illness. We found that the extent of capsule expression was influenced by culturing conditions. Our findings highlight consequent clinical and laboratory diagnostic challenges posed by such isolates.

  19. Sequence Conservation of Glycerophosphodiester Phosphodiesterase among Treponema pallidum Strains

    OpenAIRE

    Cameron, Caroline E.; Castro, Christa; Lukehart, Sheila A.; Van Voorhis, Wesley C.

    1999-01-01

    Previous investigations have demonstrated that immunization with Treponema pallidum subsp. pallidum glycerophosphodiester phosphodiesterase significantly protects rabbits from subsequent treponeme challenge. In this report, we show that the glycerophosphodiester phosphodiesterase amino acid sequence is conserved among 12 strains from a total of five pathogenic treponemes. The invariant nature of this immunoprotective antigen makes it an attractive candidate for inclusion in a universal subuni...

  20. Autogrooming by resistant honey bees challenged with individual tracheal mites

    OpenAIRE

    Danka, Robert; Villa, José

    2003-01-01

    Autogrooming responses of resistant and susceptible strains of honey bees were measured when bees were challenged by placing adult female tracheal mites on their thoraces. Marked, young adult workers of the two strains of bees were added to colonies in observation hives. We transferred a single, live, adult, female mite onto the mesoscutum of a marked bee, monitored the bee for seven minutes and then removed it and searched for the mite. Greater proportions of resistant bees autogroomed, and ...

  1. Temperature controlled strain gaged extensometer

    Science.gov (United States)

    Ramos, G. L.; Seplow, S.

    1968-01-01

    Temperature controlled strain-gaged extensometer measures longitudinal and girth deflections of pressure vessels in excess of one percent strain during pressurization and depressurization with cryogenic fluids at cryogenic temperatures. The device is of beryllium-copper strips.

  2. Targeting Importin-α7 as a Therapeutic Approach against Pandemic Influenza Viruses.

    Science.gov (United States)

    Resa-Infante, Patricia; Paterson, Duncan; Bonet, Jaume; Otte, Anna; Oliva, Baldo; Fodor, Ervin; Gabriel, Gülsah

    2015-09-01

    Viral drug resistance is believed to be less likely to occur if compounds are directed against cellular rather than viral proteins. In this study, we analyzed the feasibility of a crucial viral replication factor, namely, importin-α7, as a cellular drug target to combat pandemic influenza viruses. Surprisingly, only five viral lung-to-lung passages were required to achieve 100% lethality in importin-α7⁻/⁻ mice that otherwise are resistant. Viral escape from importin-α7 requirement was mediated by five mutations in the viral ribonucleoprotein complex and the surface glycoproteins. Moreover, the importin-α7⁻/⁻ mouse-adapted strain became even more virulent for wild-type mice than the parental strain. These studies show that targeting host proteins may still result in viral escape by alternative pathways, eventually giving rise to even more virulent virus strains. Thus, therapeutic intervention strategies should consider a multitarget approach to reduce viral drug resistance. IMPORTANCE Here, we investigated the long-standing hypothesis based on in vitro studies that viral drug resistance occurrence is less likely if compounds are directed against cellular rather than viral proteins. Here, we challenged this hypothesis by analyzing, in an in vivo animal model, the feasibility of targeting the cellular factor importin-α7, which is crucial for human influenza virus replication and pathogenesis, as an efficient antiviral strategy against pandemic influenza viruses. In summary, our studies suggest that resistance against cellular factors is possible in vivo, and the emergence of even more virulent viral escape variants calls for particular caution. Thus, therapeutic intervention strategies should consider a multitarget approach using compounds against viral as well as cellular factors to reduce the risk of viral drug resistance and potentially increased virulence. PMID:26085167

  3. Aptamers for Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Partha Ray

    2010-05-01

    Full Text Available Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX. SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer-mediated delivery.

  4. MEMS Resonant Strain Sensor Integration

    OpenAIRE

    Myers, David Richard

    2010-01-01

    Despite commercial availability since the 1950's, silicon strain sensors have not experienced the same success as other microdevices, such as accelerometers, pressure sensors, and inkjet heads. Strain sensors measure mechanical deformation and could be used in many structural components, improving safety, controls, and manufacturing tolerances. This thesis examines major strain sensing techniques and highlights both advantages and disadvantages of each. MEMS resonant strain gauges are iden...

  5. Simultaneous utilization of glucose, xylose and arabinose in the presence of acetate by a consortium of Escherichia coli strains

    Directory of Open Access Journals (Sweden)

    Xia Tian

    2012-06-01

    Full Text Available Abstract Background The efficient microbial utilization of lignocellulosic hydrolysates has remained challenging because this material is composed of multiple sugars and also contains growth inhibitors such as acetic acid (acetate. Using an engineered consortium of strains derived from Escherichia coli C and a synthetic medium containing acetate, glucose, xylose and arabinose, we report on both the microbial removal of acetate and the subsequent simultaneous utilization of the sugars. Results In a first stage, a strain unable to utilize glucose, xylose and arabinose (ALS1392, strain E. coli C ptsG manZ glk crr xylA araA removed 3 g/L acetate within 30 hours. In a subsequent second stage, three E. coli strains (ALS1370, ALS1371, ALS1391, which are each engineered to utilize only one sugar, together simultaneously utilized glucose, xylose and arabinose. The effect of non-metabolizable sugars on the metabolism of the target sugar was minimal. Additionally the deletions necessary to prevent the consumption of one sugar only minimally affected the consumption of a desired sugar. For example, the crr deletion necessary to prevent glucose consumption reduced xylose and arabinose utilization by less than 15% compared to the wild-type. Similarly, the araA deletion used to exclude arabinose consumption did not affect xylose- and glucose-consumption. Conclusions Despite the modest reduction in the overall rate of sugar consumption due to the various deletions that were required to generate the consortium of strains, the approach constitutes a significant improvement in any single-organism approach to utilize sugars found in lignocellulosic hydrolysate in the presence of acetate.

  6. Strain calibration of optical FBG-based strain sensors

    Science.gov (United States)

    Roths, Johannes; Wilfert, Andre; Kratzer, Peter; Jülich, Florian; Kuttler, Rolf

    2010-09-01

    A facility for strain sensitivity calibration of optical FBG-based strain sensors according to the German VDI/VDE 2660 guideline was established and characterized. Statistical analysis of several calibration measurement series performed with one single type of FBG strain sensor and application technique showed a reproducibility of 0.15%. Strain sensitivities for FBGs inscribed in two different types of optical fibres (GF1B and PR2008) showed significantly different strain sensitivities of k = 0.7885+/-0.0026 and k = 0.7758+/-0.0024, respectively.

  7. Precision determination of strains by strain measurement method

    International Nuclear Information System (INIS)

    Method for precision strain measurement determination of strains measurement determination of strains by direct measurement of the resistance of strain gauge resistors put on the sample, by constant current bridge MOD-61 of 0.05 class using a zero method by single bridge double-clamp circuit is described. Strain measurement technique was used to investigate residual stresses in tubular samples. Sample external diameter made up 30 mm, the length - 180, the wall thickness-11 mm. To evaluate the method sensitivity, annealed samples were investigated (annealing temperature-850-880 deg C, hold-up-2 h, cooling in the furnace). It is ascertained, that the method provides for 0.3-0.5 μm strain measurement accuracy even if sample strains do not exceed 3.0-3.6 μm and correspond to residual stress level of no more than 20 MPa

  8. Effect of P39 Gene Deletion in Live Brucella Vaccine Strains on Residual Virulence and Protective Activity in Mice

    OpenAIRE

    Tibor, Anne; Jacques, Isabelle; Guilloteau, Laurence; Verger, Jean-Michel; Grayon, Maggy; Wansard, Valerie; Letesson, Jean-Jacques

    1998-01-01

    The 39-kilodalton protein (P39) has previously been shown to be an immunodominant protein in Brucella infections. P39 gene deletion mutants of vaccine strains Brucella abortus S19 and Brucella melitensis Rev.1 were constructed by gene replacement. This deletion did not significantly modify the residual virulence of both vaccine strains in CD-1 mice. CD-1 mice vaccinated with the parent or mutant strains were protected against a virulent challenge. Mutant vaccine strains devoid of P39 could pr...

  9. Liposome Encapsulation of Ciprofloxacin Improves Protection against Highly Virulent Francisella tularensis Strain Schu S4

    OpenAIRE

    Hamblin, Karleigh A.; Armstrong, Stuart J.; Barnes, Kay B.; Davies, Carwyn; Wong, Jonathan P.; Blanchard, James D.; Harding, Sarah V.; Simpson, Andrew J. H.; Atkins, Helen S.

    2014-01-01

    Liposome-encapsulated ciprofloxacin for inhalation (CFI) was investigated as a putative postexposure therapeutic for two strains of Francisella tularensis. The efficacies of oral ciprofloxacin and intranasally instilled CFI could not be distinguished in a mouse model of infection with the F. tularensis live vaccine strain (LVS), where a single dose of either formulation offered full protection against a lethal challenge. However, mouse studies with the more virulent Schu S4 strain of F. tular...

  10. CHALLENGES IN CROSS CULTURAL ADVERTISING

    Directory of Open Access Journals (Sweden)

    Yuni Retnowati

    2015-10-01

    Full Text Available At first, marketing practitioners and academics consider standardized approaches to marketing and advertising strategies in globalization, and then some studies proved that the standardization of advertising across culture is not valid. Therefore, cross cultural advertising takes local culture into account when conveying messages in advertisements. Cross cultural understanding is very important in order to produce successful localized advertising that would reflect the cultural values and norms of intended audience. Challenge in cross cultural advertising is the problem of communicating to people of diverse cultural background. Cross cultural solutions are applied in areas such as language, communication style, images and cultural values. Cross cultural advertising is simply about using common sense and analyzing how the different elements of an advertising campaign are impacted by culture and modifying them to best speak to the target audience. Other challenges are determining between standardization and adaptation of cultural values content of advertising when facing different people from diverse cultures. In academic side, the challenge is preparing students to design advertisements that communicate effectively to diverse cultures.

  11. Nonreplicating, cyst-defective type II Toxoplasma gondii vaccine strains stimulate protective immunity against acute and chronic infection.

    Science.gov (United States)

    Fox, Barbara A; Bzik, David J

    2015-05-01

    Live attenuated vaccine strains, such as type I nonreplicating uracil auxotroph mutants, are highly effective in eliciting lifelong immunity to virulent acute infection by Toxoplasma gondii. However, it is currently unknown whether vaccine-elicited immunity can provide protection against acute infection and also prevent chronic infection. To address this problem, we developed nonreverting, nonreplicating, live attenuated uracil auxotroph vaccine strains in the type II Δku80 genetic background by targeting the deletion of the orotidine 5'-monophosphate decarboxylase (OMPDC) and uridine phosphorylase (UP) genes. Deletion of OMPDC induced a severe uracil auxotrophy with loss of replication, loss of virulence in mice, and loss of the ability to develop cysts and chronic infection. Vaccination of mice using type II Δku80 Δompdc mutants stimulated a fully protective CD8(+) T cell-dependent immunity that prevented acute infection by type I and type II strains of T. gondii, and this vaccination also severely reduced or prevented cyst formation after type II challenge infection. Nonreverting, nonreplicating, and non-cyst-forming Δompdc mutants provide new tools to examine protective immune responses elicited by vaccination with a live attenuated type II vaccine. PMID:25776745

  12. Meeting the competitive challenge: Benchmarking at FP ampersand L

    International Nuclear Information System (INIS)

    The purpose of this paper is to share the evolution of target setting at Florida Power and Light Company's (FP ampersand L's) nuclear division, including historic performance, future goals, and challenges

  13. Genetic Characterization of Bacillus anthracis 17 JB strain

    Directory of Open Access Journals (Sweden)

    Sakineh Seyed-Mohamadi

    2015-11-01

    Full Text Available Background and Objectives: Bacillus anthracis is one of the most homogenous bacteria ever described. Bacillus anthracis 17JB is a laboratory strain. It is broadly used as a challenge strain in guinea pigs for potency test of anthrax vaccine.Material and Methods: This work describes genetic characterization of B. anthracis 17 JB strain using the SNPs and MLVA genotyping.Results and Conclusion: In SNPs typing, the originally French 17JB strain represented the A. Br. 008/009 subgroup. In Levy's genotyping method, 843, 451 and 864 bp long fragments were identified at AA03, AJ03 and AA07 loci, respectively. In the vaccine manufacturer perspective these findings are much valuable on their own account, but similar research is required to extend molecular knowledge of B. anthracis epidemiology in Persia.Keywords: Bacillus anthracis 17JB, Genetic characterization, SNPs typing

  14. Development of reversible strain gage

    International Nuclear Information System (INIS)

    A high-temperature strain gage which can be peeled after taking required apparent strain measurements in a furnace and can be attached reverse-side-up at the point of interest on a test structure was developed. Using the ''reversible'' strain gage with selected room-temperature curing type polyester adhesive, one can expect to measure thermal strain accurately, especially for on large structures, at the first test in temperature up to 250 deg C. The repeatability of apparent strains for about 100 reversible gages was within 50 microstrains of difference at 250 deg C (within 30 microstrains of difference for 80 % of the test gages). (author)

  15. Novel neutralizing monoclonal antibodies protect rodents against lethal filovirus challenges

    Directory of Open Access Journals (Sweden)

    Caleb D. Marceau

    2014-01-01

    Full Text Available Filoviruses are the causative agents of lethal hemorrhagic fever in human and non-human primates (NHP. The family of Filoviridae is composed of three genera, Ebolavirus, Marburgvirus and Cuevavirus. There are currently no approved vaccines or antiviral therapeutics for the treatment of filovirus infections in humans. Passive transfer of neutralizing antibodies targeting the Ebola virus (EBOV glycoprotein (GP has proven effective in protecting mice, guinea pigs and NHP from lethal challenges with EBOV. In this study, we generated two neutralizing monoclonal antibodies (MAbs, termed S9 and M4 that recognize the GP of EBOV or multiple strains of Marburg virus (MARV, respectively. We characterized the putative binding site of S9 as a linear epitope on the glycan cap of the GP1 subunit of the EBOV-GP. The M4 antibody recognizes an unknown conformational epitope on MARV-GP. Additionally, we demonstrated the post-exposure protection potential of these antibodies in both the mouse and guinea pig models of filovirus infection. These data indicate that MAbs S9 and M4 would be good candidates for inclusion in an antibody cocktail for the treatment of filovirus infections.

  16. The GREAT3 Challenge

    OpenAIRE

    Miyatake, Hironao; Mandelbaum, Rachel; collaboration, Barnaby Rowe on behalf of the GREAT3

    2014-01-01

    The GRavitational lEnsing Accuracy Testing 3 (GREAT3) challenge is an image analysis competition that aims to test algorithms to measure weak gravitational lensing from astronomical images. The challenge started in October 2013 and ends 30 April 2014. The challenge focuses on testing the impact on weak lensing measurements of realistically complex galaxy morphologies, realistic point spread function, and combination of multiple different exposures. It includes simulated ground- and space-base...

  17. [Echinococcus and strain concepts].

    Science.gov (United States)

    Utük, Armağan Erdem; Simsek, Sami

    2008-01-01

    Hydatid disease (echinococcosis) is one of the most important parasitic zoonoses and remains a public health and economic problem all over the world. Echinococcus granulosus includes a number of genetic variants and, up to date, analyses of mitochondrial DNA sequences have identified ten distinct genetic types (genotypes G1-10). This categorization follows closely the pattern of strain variation emerging based on biological characteristics. The extensive variation in E. granulosus may influence life-cycle patterns, host specificity, development rate, antigenicity, transmission dynamics, sensitivity to chemotherapeutic agents, and pathology. In this review, the recent genetic characterizations of Echinococcus genus have been summarized. PMID:18351549

  18. Asymptomatic bacteriuria Escherichia coli strains

    DEFF Research Database (Denmark)

    Hancock, Viktoria; Nielsen, E.M.; Klemm, Per

    2006-01-01

    Urinary tract infections (UTIs) affect millions of people each year. Escherichia coli is the most common organism associated with asymptomatic bacteriuria (ABU) in humans. Persons affected by ABU may carry a particular E. coli strain for extended periods of time without any symptoms. In contrast to...... uropathogenic E. coli (UPEC) that cause symptomatic UTI, very little is known about the mechanisms by which these strains colonize the urinary tract. Here, we have investigated the growth characteristics in human urine as well as adhesin repertoire of nine ABU strains; the ability of ABU strains to compete...... against the UPEC strain CFT073 was also studied. The different ABU strains displayed a wide variety of the measured characteristics. Half of the ABU strains displayed functional type 1 fimbriae while only one expressed functional P fimbriae. A good correlation between the growth rate of a particular...

  19. Challenges of Relativistic Astrophysics

    CERN Document Server

    Opher, Reuven

    2013-01-01

    I discuss some of the most outstanding challenges in relativistic astrophysics in the subjects of: compact objects (Black Holes and Neutron Stars); dark sector (Dark Matter and Dark Energy); plasma astrophysics (Origin of Jets, Cosmic Rays and Magnetic Fields) and the primordial universe (Physics at the beginning of the Universe). In these four subjects, I discuss twelve of the most important challenges. These challenges give us insight into new physics that can only be studied in the large scale Universe. The near future possibilities, in observations and theory, for addressing these challenges, are also discussed.

  20. Challenges and Opportunities for Regeneration in the Peripheral Nervous System

    OpenAIRE

    Höke, Ahmet; Brushart, Thomas

    2009-01-01

    Regeneration in the peripheral nervous system offers unique opportunities and challenges to medicine. Compared to the central nervous system, peripheral axons can and do regenerate resulting in functional recovery, especially if the distance to target is short as in distal limb injuries. However, this regenerative capacity is often incomplete and functional recovery with proximal lesions is limited. Furthermore, regeneration of axons to the appropriate targets remains a challenge with inappro...

  1. Systems strategies for developing industrial microbial strains.

    Science.gov (United States)

    Lee, Sang Yup; Kim, Hyun Uk

    2015-10-01

    Industrial strain development requires system-wide engineering and optimization of cellular metabolism while considering industrially relevant fermentation and recovery processes. It can be conceptualized as several strategies, which may be implemented in an iterative fashion and in different orders. The key challenges have been the time-, cost- and labor-intensive processes of strain development owing to the difficulties in understanding complex interactions among the metabolic, gene regulatory and signaling networks at the cell level, which are collectively represented as overall system performance under industrial fermentation conditions. These challenges can be overcome by taking systems approaches through the use of state-of-the-art tools of systems biology, synthetic biology and evolutionary engineering in the context of industrial bioprocess. Major systems metabolic engineering achievements in recent years include microbial production of amino acids (L-valine, L-threonine, L-lysine and L-arginine), bulk chemicals (1,4-butanediol, 1,4-diaminobutane, 1,5-diaminopentane, 1,3-propanediol, butanol, isobutanol and succinic acid) and drugs (artemisinin). PMID:26448090

  2. Controlling surface reactions with nanopatterned surface elastic strain.

    Science.gov (United States)

    Li, Zhisheng; Potapenko, Denis V; Osgood, Richard M

    2015-01-27

    The application of elastic lattice strain is a promising approach for tuning material properties, but the attainment of a systematic approach for introducing a high level of strain in materials so as to study its effects has been a major challenge. Here we create an array of intense locally varying strain fields on a TiO2 (110) surface by introducing highly pressurized argon nanoclusters at 6-20 monolayers under the surface. By combining scanning tunneling microscopy imaging and the continuum mechanics model, we show that strain causes the surface bridge-bonded oxygen vacancies (BBOv), which are typically present on this surface, to be absent from the strained area and generates defect-free regions. In addition, we find that the adsorption energy of hydrogen binding to oxygen (BBO) is significantly altered by local lattice strain. In particular, the adsorption energy of hydrogen on BBO rows is reduced by ∼ 35 meV when the local crystal lattice is compressed by ∼ 1.3%. Our results provide direct evidence of the influence of strain on atomic-scale surface chemical properties, and such effects may help guide future research in catalysis materials design. PMID:25494489

  3. Interferometric strain measurements with a fiber-optic probe

    Science.gov (United States)

    Burnham-Fay, E. D.; Jacobs-Perkins, D. W.; Ellis, J. D.

    2015-09-01

    Experience at the Laboratory for Laser Energetics has shown that broadband base vibrations make it difficult to position cryogenic inertial confinement fusion targets. These effects must be mitigated for National Ignition Facility-scale targets; to this end an active vibration stabilization system is proposed. A single-mode optical fiber strain probe and a novel fiber contained heterodyne interferometer have been developed as a position feedback sensor for the vibration control system. A resolution limit of 54.5 nƐ; is measured with the optical strain gauge, limited by the lock-in amplifier. Experimental measurements of the sensor that show good agreement with reference resistive strain gauge measurements are presented.

  4. 78 FR 70303 - Announcement of Requirements and Registration for the Predict the Influenza Season Challenge

    Science.gov (United States)

    2013-11-25

    ..., targeting resources and therefore reducing costs associated with influenza prevention and control, and... contest. Information is not collected for commercial marketing. Registering through the Challenge.gov...

  5. Angiogenesis is induced by airway smooth muscle strain.

    Science.gov (United States)

    Hasaneen, Nadia A; Zucker, Stanley; Lin, Richard Z; Vaday, Gayle G; Panettieri, Reynold A; Foda, Hussein D

    2007-10-01

    Angiogenesis is an important feature of airway remodeling in both chronic asthma and chronic obstructive pulmonary disease (COPD). Airways in those conditions are exposed to excessive mechanical strain during periods of acute exacerbations. We recently reported that mechanical strain of human airway smooth muscle (HASM) led to an increase in their proliferation and migration. Sustained growth in airway smooth muscle in vivo requires an increase in the nutritional supply to these muscles, hence angiogenesis. In this study, we examined the hypothesis that cyclic mechanical strain of HASM produces factors promoting angiogenic events in the surrounding vascular endothelial cells. Our results show: 1) a significant increase in human lung microvascular endothelial cell (HMVEC-L) proliferation, migration, and tube formation following incubation in conditioned media (CM) from HASM cells exposed to mechanical strain; 2) mechanical strain of HASM cells induced VEGF expression and release; 3) VEGF neutralizing antibodies inhibited the proliferation, migration, and tube formations of HMVEC-L induced by the strained airway smooth muscle CM; 4) mechanical strain of HASM induced a significant increase in hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA and protein, a transcription factor required for VEGF gene transcription; and 5) mechanical strain of HASM induced HIF-1alpha/VEGF through dual phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and ERK pathways. In conclusion, exposing HASM cells to mechanical strain induces signal transduction pathway through PI3K/Akt/mTOR and ERK pathways that lead to an increase in HIF-1alpha, a transcription factor required for VEGF expression. VEGF release by mechanical strain of HASM may contribute to the angiogenesis seen with repeated exacerbation of asthma and COPD. PMID:17693481

  6. Science Challenge Day

    Science.gov (United States)

    Siegel, Deborah

    2013-01-01

    Science fairs can be good motivators, but as extracurricular activities, they leave some students behind. However, by staging a Science Challenge Day at school, educators can involve all students in doing everything from choosing activities to judging projects. This article presents a model for running a successful Science Challenge Day. The…

  7. Overcoming Breastfeeding Challenges

    Medline Plus

    Full Text Available ... size | Print | Skip left navigation It's Only Natural Planning ahead Overcoming challenges Overcoming breastfeeding challenges Dealing with ... it into your life My breastfeeding story Partner resources Subscribe ... at the U.S. Department of Health and Human Services 200 Independence Avenue, S.W. • Washington, DC 20201 ...

  8. First Aid Challenge

    Science.gov (United States)

    Roman, Harry T.

    2011-01-01

    This article describes a challenge wherein students will be asked to design a portable first aid kit that is normally carried in a recreational vehicle (RV), but can also be hand-carried or backpacked off road for distances of approximately 1-2 miles. This can be a very practical challenge for the students because it touches everyone. Everybody…

  9. Strain in Hydrogen-Implanted Si Investigated Using Dark-Field Electron Holography

    Science.gov (United States)

    Cherkashin, Nikolay; Reboh, Shay; Lubk, Axel; Hÿtch, Martin J.; Claverie, Alain

    2013-09-01

    The microstructure of ion-implanted crystals is profoundly dictated by mechanical strain developing in interplay with structural defects. Understanding the origin of strain during the early stages of development is challenging and requires accurate measurements and modeling. Here, we investigate the mechanical strain in H-implanted Si. X-ray diffraction analysis is performed to measure the mesoscopic out-of-plane strain and dark-field electron holography to map strain in two-dimensions (2D) with nanometer spatial resolution. Supported by finite element method modeling, we propose that the mean strain field is explained by overlapping and averaging discrete strain fields generated by sub-nanoscopic defects that are intimately related to the H depth concentration.

  10. Retaining Large and Adjustable Elastic Strains of Kilogram-Scale Nb Nanowires

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Shijie; Cui, Lishan; Wang, Hua; Jiang, Daqiang; Liu, Yinong; Yan, Jiaqiang; Ren, Yang; Han, Xiaodong; Brown, Dennis E.; Li, Ju

    2016-02-10

    Individual metallic nanowires can sustain ultra-large elastic strains of 4-7%. However, achieving and retaining elastic strains of such magnitude in kilogram-scale nanowires are challenging. Here, we find that under active load, ~5.6% elastic strain can be achieved in Nb nanowires embedded in a metallic matrix deforming by detwinning. Moreover, large tensile (2.8%) and compressive (-2.4%) elastic strains can be retained in kilogram-scale Nb nanowires when the external load was fully removed, and adjustable in magnitude by processing control. It is then demonstrated that the retained tensile elastic strains of Nb nanowires can increase their superconducting transition temperature and critical magnetic field, in comparison with the unstrained original material. This study opens new avenues for retaining large and tunable elastic strains in great quantities of nanowires and elastic-strain-engineering at industrial scale.

  11. Automatic target tracking in FLIR image sequences

    Science.gov (United States)

    Bal, Abdullah; Alam, Mohammad S.

    2004-09-01

    Moving target tracking is a challenging task and is increasingly becoming important for various applications. In this paper, we have presented target detection and tracking algorithm based on target intensity feature relative to surrounding background, and shape information of target. Proposed automatic target tracking algorithm includes two techniques: intensity variation function (IVF) and template modeling (TM). The intensity variation function is formulated by using target intensity feature while template modeling is based on target shape information. The IVF technique produces the maximum peak value whereas the reference target intensity variation is similar to the candidate target intensity variation. When IVF technique fails, due to background clutter, non-target object or other artifacts, the second technique, template modeling, is triggered by control module. By evaluating the outputs from the IVF and TM techniques, the tracker determines the real coordinates of the target. Performance of the proposed ATT is tested using real life forward-looking infrared (FLIR) image sequences taken from an airborne, moving platform.

  12. Fighting power, targeting and cyber operations

    OpenAIRE

    Ducheine, P.A.L.; Haaster, van, A.J.M.

    2014-01-01

    This article aims to contribute to the operationalisation of military cyber operations in general, and for targeting purposes (either in defence or offence) in particular. The position of cyber operations in military doctrine will be clarified, their contribution to fighting power conceptualised and the ramifications on targeting processes discussed. Cyberspace poses unique challenges and opportunities; we distinguish new elements that may be utilized for ‘targeting’, namely: cyber objects an...

  13. In Vitro Susceptibility of Various Genotypic Strains of Toxoplasma gondii to Pyrimethamine, Sulfadiazine, and Atovaquone▿

    OpenAIRE

    Meneceur, Pascale; Bouldouyre, Marie-Anne; Aubert, Dominique; Villena, Isabelle; Menotti, Jean; Sauvage, Virginie; Garin, Jean-François; Derouin, Francis

    2008-01-01

    Sulfadiazine, pyrimethamine, and atovaquone are widely used for the treatment of severe toxoplasmosis. Their in vitro activities have been almost exclusively demonstrated on laboratory strains belonging to genotype I. We determined the in vitro activities of these drugs against 17 strains of Toxoplasma gondii belonging to various genotypes and examined the correlations among 50% inhibitory concentrations (IC50s), growth kinetics, strain genotypes, and mutations on drug target genes. Growth ki...

  14. A Comparative Study of Strain- and Shear-Wave-Elastography in an Elasticity Phantom

    DEFF Research Database (Denmark)

    Carlsen, Jonathan F; Pedersen, Malene R; Ewertsen, Caroline; Săftoiu, Adrian; Lönn, Lars; Rafaelsen, Søren R; Nielsen, Michael B

    2015-01-01

    OBJECTIVE. The purpose of this study was to assess the diagnostic accuracy of strain and shear-wave elastography for determining targets of varying stiffness in a phantom. The effect of target diameter on elastographic assessments and the effect of depth on shear-wave velocity were also investiga......OBJECTIVE. The purpose of this study was to assess the diagnostic accuracy of strain and shear-wave elastography for determining targets of varying stiffness in a phantom. The effect of target diameter on elastographic assessments and the effect of depth on shear-wave velocity were also...

  15. SVAS3: Strain Vector Aided Sensorization of Soft Structures

    Directory of Open Access Journals (Sweden)

    Utku Culha

    2014-07-01

    Full Text Available Soft material structures exhibit high deformability and conformability which can be useful for many engineering applications such as robots adapting to unstructured and dynamic environments. However, the fact that they have almost infinite degrees of freedom challenges conventional sensory systems and sensorization approaches due to the difficulties in adapting to soft structure deformations. In this paper, we address this challenge by proposing a novel method which designs flexible sensor morphologies to sense soft material deformations by using a functional material called conductive thermoplastic elastomer (CTPE. This model-based design method, called Strain Vector Aided Sensorization of Soft Structures (SVAS3, provides a simulation platform which analyzes soft body deformations and automatically finds suitable locations for CTPE-based strain gauge sensors to gather strain information which best characterizes the deformation. Our chosen sensor material CTPE exhibits a set of unique behaviors in terms of strain length electrical conductivity, elasticity, and shape adaptability, allowing us to flexibly design sensor morphology that can best capture strain distributions in a given soft structure. We evaluate the performance of our approach by both simulated and real-world experiments and discuss the potential and limitations.

  16. Target Awareness: Lupus

    Science.gov (United States)

    ... Target Awareness: Lupus Jan. 15, 2009 Target Awareness: Lupus Target Awareness: Lupus provides a brief overview of ... Email Print Tags for this Story treatments symptoms Lupus FAQ What is lupus? What are the common ...

  17. Target Awareness: Lupus

    Medline Plus

    Full Text Available ... Target Awareness: Lupus Jan. 15, 2009 Target Awareness: Lupus Target Awareness: Lupus provides a brief overview of ... Email Print Tags for this Story treatments symptoms Lupus FAQ What is lupus? What are the common ...

  18. Target factory in perspective

    International Nuclear Information System (INIS)

    A target factory diagram has been constructed for an analysis of the shell coating process system in relation to target production. The number of deposition units needed to achieve the coating requirements will be a major target production operating cost

  19. Genetic Manipulation in Δku80 Strains for Functional Genomic Analysis of Toxoplasma gondii

    OpenAIRE

    Rommereim, Leah M.; Hortua Triana, Miryam A.; Falla, Alejandra; Sanders, Kiah L; Guevara, Rebekah B.; Bzik, David J.; Fox, Barbara A.

    2013-01-01

    Targeted genetic manipulation using homologous recombination is the method of choice for functional genomic analysis to obtain a detailed view of gene function and phenotype(s). The development of mutant strains with targeted gene deletions, targeted mutations, complemented gene function, and/or tagged genes provides powerful strategies to address gene function, particularly if these genetic manipulations can be efficiently targeted to the gene locus of interest using integration mediated by ...

  20. Suppression of aggressive strains of 'Candidatus phytoplasma mali' by mild strains in Catharanthus roseus and Nicotiana occidentalis and indication of similar action in apple trees.

    Science.gov (United States)

    Schneider, Bernd; Sule, Sandor; Jelkmann, Wilhelm; Seemüller, Erich

    2014-05-01

    To study antagonistic interactions of 'Candidatus Phytoplasma mali' strains, graft inoculation of Catharanthus roseus and Nicotiana occidentalis was performed with mild strains 1/93Vin and 1/93Tab as suppressors and three aggressive strains as challengers. Inoculation of the suppressors was carried out in either the cross-protection modus prior to grafting of the challengers or by co-inoculating suppressors and challengers. Monitoring using multiplex real-time polymerase chain reaction assays revealed that, in long-term cross-protection trials with C. roseus, suppressor 1/93Vin was present in all root and randomly collected stem samples over the entire observation period. In contrast, the challengers were never detected in such stem samples and rarely in the roots. Following simultaneous inoculation, the suppressor successively colonized all stem and root regions whereas detection of challenger AT steadily decreased. However, this strain remained detectable in up to 13 and 27% of stem and root samples, respectively. The cross-protection trials with N. occidentalis yielded results similar to that of the cross-protection experiments with C. roseus. Comparison of the symptomatology of infected apple trees with the presence of putatively suppressive strains indicated that suppression of severe strains also occurs in apple. Phylogenetic analysis using a variable fragment of AAA+ ATPase gene AP460 of 'Ca. P. mali' revealed that suppressors 1/93Vin and 1/93Tab, together with several other mild strains maintained in apple, cluster distantly from obviously nonsuppressive strains that were predominantly highly virulent. PMID:24724815

  1. Erwinia amylovora CRISPR elements provide new tools for evaluating strain diversity and for microbial source tracking.

    Directory of Open Access Journals (Sweden)

    Gayle C McGhee

    Full Text Available Clustered regularly interspaced short palindromic repeats (CRISPRs comprise a family of short DNA repeat sequences that are separated by non repetitive spacer sequences and, in combination with a suite of Cas proteins, are thought to function as an adaptive immune system against invading DNA. The number of CRISPR arrays in a bacterial chromosome is variable, and the content of each array can differ in both repeat number and in the presence or absence of specific spacers. We utilized a comparative sequence analysis of CRISPR arrays of the plant pathogen Erwinia amylovora to uncover previously unknown genetic diversity in this species. A total of 85 E. amylovora strains varying in geographic isolation (North America, Europe, New Zealand, and the Middle East, host range, plasmid content, and streptomycin sensitivity/resistance were evaluated for CRISPR array number and spacer variability. From these strains, 588 unique spacers were identified in the three CRISPR arrays present in E. amylovora, and these arrays could be categorized into 20, 17, and 2 patterns types, respectively. Analysis of the relatedness of spacer content differentiated most apple and pear strains isolated in the eastern U.S. from western U.S. strains. In addition, we identified North American strains that shared CRISPR genotypes with strains isolated on other continents. E. amylovora strains from Rubus and Indian hawthorn contained mostly unique spacers compared to apple and pear strains, while strains from loquat shared 79% of spacers with apple and pear strains. Approximately 23% of the spacers matched known sequences, with 16% targeting plasmids and 5% targeting bacteriophage. The plasmid pEU30, isolated in E. amylovora strains from the western U.S., was targeted by 55 spacers. Lastly, we used spacer patterns and content to determine that streptomycin-resistant strains of E. amylovora from Michigan were low in diversity and matched corresponding streptomycin-sensitive strains

  2. Erwinia amylovora CRISPR elements provide new tools for evaluating strain diversity and for microbial source tracking.

    Science.gov (United States)

    McGhee, Gayle C; Sundin, George W

    2012-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPRs) comprise a family of short DNA repeat sequences that are separated by non repetitive spacer sequences and, in combination with a suite of Cas proteins, are thought to function as an adaptive immune system against invading DNA. The number of CRISPR arrays in a bacterial chromosome is variable, and the content of each array can differ in both repeat number and in the presence or absence of specific spacers. We utilized a comparative sequence analysis of CRISPR arrays of the plant pathogen Erwinia amylovora to uncover previously unknown genetic diversity in this species. A total of 85 E. amylovora strains varying in geographic isolation (North America, Europe, New Zealand, and the Middle East), host range, plasmid content, and streptomycin sensitivity/resistance were evaluated for CRISPR array number and spacer variability. From these strains, 588 unique spacers were identified in the three CRISPR arrays present in E. amylovora, and these arrays could be categorized into 20, 17, and 2 patterns types, respectively. Analysis of the relatedness of spacer content differentiated most apple and pear strains isolated in the eastern U.S. from western U.S. strains. In addition, we identified North American strains that shared CRISPR genotypes with strains isolated on other continents. E. amylovora strains from Rubus and Indian hawthorn contained mostly unique spacers compared to apple and pear strains, while strains from loquat shared 79% of spacers with apple and pear strains. Approximately 23% of the spacers matched known sequences, with 16% targeting plasmids and 5% targeting bacteriophage. The plasmid pEU30, isolated in E. amylovora strains from the western U.S., was targeted by 55 spacers. Lastly, we used spacer patterns and content to determine that streptomycin-resistant strains of E. amylovora from Michigan were low in diversity and matched corresponding streptomycin-sensitive strains from the

  3. Strain in silicon nanowire beams

    Science.gov (United States)

    Ureña, Ferran; Olsen, Sarah H.; Šiller, Lidija; Bhaskar, Umesh; Pardoen, Thomas; Raskin, Jean-Pierre

    2012-12-01

    In this work, strain in silicon free standing beams loaded in uniaxial tension is experimentally and theoretically investigated for strain values ranging from 0 to 3.6%. The fabrication method allows multiple geometries (and thus strain values) to be processed simultaneously on the same wafer while being studied independently. An excellent agreement of strain determined by two non-destructive characterization techniques, Raman spectroscopy and mechanical displacement using scanning electron microscopy (SEM) markers, is found for all the sample lengths and widths. The measured data also show good agreement with theoretical predictions of strain based upon continuum mechanical considerations, giving validity to both measurement techniques for the entire range of strain values. The dependence of Young's modulus and fracture strain on size has also been analyzed. The Young's modulus is determined using SEM and compared with that obtained by resonance-based methods. Both methods produced a Young's modulus value close to that of bulk silicon with values obtained by resonance-based methods being slightly lower. Fracture strain is analyzed in 40 sets of samples with different beam geometries, yielding values up to 3.6%. The increase in fracture strain with decreasing beam width is compared with previous reports. Finally, the role of the surface on the mechanical properties is analyzed using UV and visible lasers having different penetration depths in silicon. The observed dependence of Raman shift on laser wavelength is used to assess the thermal conductivity of deformed silicon.

  4. Asymptomatic bacteriuria Escherichia coli strains

    DEFF Research Database (Denmark)

    Hancock, Viktoria; Nielsen, E.M.; Klemm, Per

    2006-01-01

    Urinary tract infections (UTIs) affect millions of people each year. Escherichia coli is the most common organism associated with asymptomatic bacteriuria (ABU) in humans. Persons affected by ABU may carry a particular E. coli strain for extended periods of time without any symptoms. In contrast to...... uropathogenic E. coli (UPEC) that cause symptomatic UTI, very little is known about the mechanisms by which these strains colonize the urinary tract. Here, we have investigated the growth characteristics in human urine as well as adhesin repertoire of nine ABU strains; the ability of ABU strains to compete...

  5. Hydrogen production from microbial strains

    Science.gov (United States)

    Harwood, Caroline S; Rey, Federico E

    2012-09-18

    The present invention is directed to a method of screening microbe strains capable of generating hydrogen. This method involves inoculating one or more microbes in a sample containing cell culture medium to form an inoculated culture medium. The inoculated culture medium is then incubated under hydrogen producing conditions. Once incubating causes the inoculated culture medium to produce hydrogen, microbes in the culture medium are identified as candidate microbe strains capable of generating hydrogen. Methods of producing hydrogen using one or more of the microbial strains identified as well as the hydrogen producing strains themselves are also disclosed.

  6. Yersinia pestis biovar Microtus strain 201, an avirulent strain to humans, provides protection against bubonic plague in rhesus macaques.

    Science.gov (United States)

    Zhang, Qingwen; Wang, Qiong; Tian, Guang; Qi, Zhizhen; Zhang, Xuecan; Wu, Xiaohong; Qiu, Yefeng; Bi, Yujing; Yang, Xiaoyan; Xin, Youquan; He, Jian; Zhou, Jiyuan; Zeng, Lin; Yang, Ruifu; Wang, Xiaoyi

    2014-01-01

    Yersinia pestis biovar Microtus is considered to be a virulent to larger mammals, including guinea pigs, rabbits and humans. It may be used as live attenuated plague vaccine candidates in terms of its low virulence. However, the Microtus strain's protection against plague has yet to be demonstrated in larger mammals. In this study, we evaluated the protective efficacy of the Microtus strain 201 as a live attenuated plague vaccine candidate. Our results show that this strain is highly attenuated by subcutaneous route, elicits an F1-specific antibody titer similar to the EV and provides a protective efficacy similar to the EV against bubonic plague in Chinese-origin rhesus macaques. The Microtus strain 201 could induce elevated secretion of both Th1-associated cytokines (IFN-γ, IL-2 and TNF-α) and Th2-associated cytokines (IL-4, IL-5, and IL-6), as well as chemokines MCP-1 and IL-8. However, the protected animals developed skin ulcer at challenge site with different severity in most of the immunized and some of the EV-immunized monkeys. Generally, the Microtus strain 201 represented a good plague vaccine candidate based on its ability to generate strong humoral and cell-mediated immune responses as well as its good protection against high dose of subcutaneous virulent Y. pestis challenge. PMID:24225642

  7. Community composition of target vs. non-target fungi in fungicide treated wheat

    DEFF Research Database (Denmark)

    Knorr, Kamilla; Jørgensen, Lise Nistrup; Justesen, Annemarie Fejer;

    2012-01-01

    Fungicide treatments are common control strategies used to manage fungal pathogens in agricultural fields, however, effects of treatments on the composition of total fungal communities, including non-target fungi, in the phyllosphere is not well known. Yellow rust (Puccinia striiformis) is a common...... disease in wheat and within the last decade, new aggressive strains of yellow rust has caused severe epidemics that lead to substantial yield losses. This study explored the community composition of target versus non-target fungi in yellow rust infected wheat as affected by treatment timing and dose of...

  8. TargetMine, an integrated data warehouse for candidate gene prioritisation and target discovery.

    Directory of Open Access Journals (Sweden)

    Yi-An Chen

    Full Text Available Prioritising candidate genes for further experimental characterisation is a non-trivial challenge in drug discovery and biomedical research in general. An integrated approach that combines results from multiple data types is best suited for optimal target selection. We developed TargetMine, a data warehouse for efficient target prioritisation. TargetMine utilises the InterMine framework, with new data models such as protein-DNA interactions integrated in a novel way. It enables complicated searches that are difficult to perform with existing tools and it also offers integration of custom annotations and in-house experimental data. We proposed an objective protocol for target prioritisation using TargetMine and set up a benchmarking procedure to evaluate its performance. The results show that the protocol can identify known disease-associated genes with high precision and coverage. A demonstration version of TargetMine is available at http://targetmine.nibio.go.jp/.

  9. Structural changes, roles and challenges

    International Nuclear Information System (INIS)

    Statnett is facing great challenges in a Nordic and European integrated power market, with increasingly mighty commercial players. In a competing market there are conflicts between the socio-economic targets for Statkraft's activities and the commercial interests of Statnet's customers and other players in the power market. In the light of development, the connection lines between the customers and Statnett should be changed. Another problem is the legal competence problem that arises when the Oil and Energy Department (OED) works out the general policy at the same time as it owns Statkraft and Statnett and is the appellate body for the development decisions taken by the NVE (the Norwegian Water Resources and Energy Directorate). When comprehensive changes in Statkraft's company organisation and ownership are considered, special attention must be paid to the competence problem and to the risk of the commercial producers increasing their impact on how Statnett manages its role as a systems operator

  10. The challenges of dismantling

    International Nuclear Information System (INIS)

    This document gathers Power Point presentations which address the contexts and challenges of dismantling (legal framework, safety and radiation protection challenges, waste processing industry), and propose illustrations of dismantling challenges (example of operations to prepare EURODIF dismantling and CLIGEET work-group on EURODIF dismantling, examples of dismantling of EDF installations and CLIs' opinion on the dismantling of EDF installations, Brennilis dismantling follow-up performed by the CLI, examples of dismantling of CEA installations and opinion of a CLI on the dismantling of CEA installations)

  11. Challenges of serious games

    Directory of Open Access Journals (Sweden)

    B. Fernández-Manjón

    2015-11-01

    Full Text Available Although educational games have revealed to be a very effective focus in diverse situations, their use in education is still very limited. In this paper we analyse the main challenges concerning educational games that, from our perspective, have to be approached so that the use of this kind of games can be widespread. These challenges are classified in three main dimensions: socio-cultural, educational and technological. Once the challenges are identified, some possible measures are suggested to address or reduce these problems so that the use of educational games may be widespread.

  12. Big Data Challenges

    Directory of Open Access Journals (Sweden)

    Alexandru Adrian TOLE

    2013-10-01

    Full Text Available The amount of data that is traveling across the internet today, not only that is large, but is complex as well. Companies, institutions, healthcare system etc., all of them use piles of data which are further used for creating reports in order to ensure continuity regarding the services that they have to offer. The process behind the results that these entities requests represents a challenge for software developers and companies that provide IT infrastructure. The challenge is how to manipulate an impressive volume of data that has to be securely delivered through the internet and reach its destination intact. This paper treats the challenges that Big Data creates.

  13. Will the swine strain crowd out the seasonal influenza strain?

    CERN Document Server

    Schinazi, Rinaldo B

    2010-01-01

    We use spatial and non spatial models to argue that competition alone may explain why two influenza strains do not usually coexist. The more virulent strain is likely to crowd out the less virulent one. This can be seen as a consequence of the Exclusion Principle of Ecology. We exhibit, however, a spatial model for which coexistence is possible.

  14. Tissue Velocity, Strain und Strain Rate bei Hunden mit Mitralklappenendokardiose

    OpenAIRE

    Javornik, Ana

    2007-01-01

    In der vorliegenden Arbeit „Tissue Velocity, Strain und Strain Rate bei Hunden mit Mitralklappenendokardiose“ wurden erstmals die Geschwindigkeits- und Verformungsparameter zur Evaluierung von Hunden mit Mitralklappenendokardiose angewendet. Diese erweisen sich als neue und viel versprechende Möglichkeiten zur Quantifizierung der regionalen Myokardfunktion. Die myokardialen Funktionsparameter finden in der Humanmedizin weit verbreitete Anwendung und auch in der Tiermedizin erlangen sie zunehm...

  15. Genetic manipulation in Δku80 strains for functional genomic analysis of Toxoplasma gondii.

    Science.gov (United States)

    Rommereim, Leah M; Hortua Triana, Miryam A; Falla, Alejandra; Sanders, Kiah L; Guevara, Rebekah B; Bzik, David J; Fox, Barbara A

    2013-01-01

    Targeted genetic manipulation using homologous recombination is the method of choice for functional genomic analysis to obtain a detailed view of gene function and phenotype(s). The development of mutant strains with targeted gene deletions, targeted mutations, complemented gene function, and/or tagged genes provides powerful strategies to address gene function, particularly if these genetic manipulations can be efficiently targeted to the gene locus of interest using integration mediated by double cross over homologous recombination. Due to very high rates of nonhomologous recombination, functional genomic analysis of Toxoplasma gondii has been previously limited by the absence of efficient methods for targeting gene deletions and gene replacements to specific genetic loci. Recently, we abolished the major pathway of nonhomologous recombination in type I and type II strains of T. gondii by deleting the gene encoding the KU80 protein(1,2). The Δku80 strains behave normally during tachyzoite (acute) and bradyzoite (chronic) stages in vitro and in vivo and exhibit essentially a 100% frequency of homologous recombination. The Δku80 strains make functional genomic studies feasible on the single gene as well as on the genome scale(1-4). Here, we report methods for using type I and type II Δku80Δhxgprt strains to advance gene targeting approaches in T. gondii. We outline efficient methods for generating gene deletions, gene replacements, and tagged genes by targeted insertion or deletion of the hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT) selectable marker. The described gene targeting protocol can be used in a variety of ways in Δku80 strains to advance functional analysis of the parasite genome and to develop single strains that carry multiple targeted genetic manipulations. The application of this genetic method and subsequent phenotypic assays will reveal fundamental and unique aspects of the biology of T. gondii and related significant human

  16. Stochastic precision analysis of 2D cardiac strain estimation in vivo

    International Nuclear Information System (INIS)

    Ultrasonic strain imaging has been applied to echocardiography and carries great potential to be used as a tool in the clinical setting. Two-dimensional (2D) strain estimation may be useful when studying the heart due to the complex, 3D deformation of the cardiac tissue. Increasing the framerate used for motion estimation, i.e. motion estimation rate (MER), has been shown to improve the precision of the strain estimation, although maintaining the spatial resolution necessary to view the entire heart structure in a single heartbeat remains challenging at high MERs. Two previously developed methods, the temporally unequispaced acquisition sequence (TUAS) and the diverging beam sequence (DBS), have been used in the past to successfully estimate in vivo axial strain at high MERs without compromising spatial resolution. In this study, a stochastic assessment of 2D strain estimation precision is performed in vivo for both sequences at varying MERs (65, 272, 544, 815 Hz for TUAS; 250, 500, 1000, 2000 Hz for DBS). 2D incremental strains were estimated during left ventricular contraction in five healthy volunteers using a normalized cross-correlation function and a least-squares strain estimator. Both sequences were shown capable of estimating 2D incremental strains in vivo. The conditional expected value of the elastographic signal-to-noise ratio (E(SNRe|ε)) was used to compare strain estimation precision of both sequences at multiple MERs over a wide range of clinical strain values. The results here indicate that axial strain estimation precision is much more dependent on MER than lateral strain estimation, while lateral estimation is more affected by strain magnitude. MER should be increased at least above 544 Hz to avoid suboptimal axial strain estimation. Radial and circumferential strain estimations were influenced by the axial and lateral strain in different ways. Furthermore, the TUAS and DBS were found to be of comparable precision at similar MERs. (paper)

  17. Toward a Better Understanding of the Effects of Hindrance and Challenge Stressors on Work Behavior

    Science.gov (United States)

    Webster, Jennica R.; Beehr, Terry A.; Christiansen, Neil D.

    2010-01-01

    This study investigated the processes whereby hindrance and challenge stressors may affect work behavior. Three mechanisms were examined to explain the differential effects these stressors have demonstrated: job satisfaction, strains, and work self-efficacy. A model is proposed in which both types of stressors will result in increases in strains,…

  18. Virulent Properties of Russian Bovine Viral Diarrhea Virus Strains in Experimentally Infected Calves

    OpenAIRE

    Glotov, Alexander G.; Tatyana I. Glotova; Koteneva, Svetlana V.; Semenova, Olga V.; Alexander A. Sergeev; Titova, Ksenya A.; Morozova, Anastasia A.; Sergeev, Artemiy A.

    2016-01-01

    The results of experimental study of three noncytopathic and two cytopathic bovine viral diarrhea virus (BVDV) strains isolated from cattle in the Siberian region and belonging to the type 1 (subtypes 1a, 1b, and 1d) have been presented. All investigated strains caused the development of infectious process in the seronegative 4–6-month-old calves after aerosol challenge with the dose of 6 log10 TCID50. The greatest virulence had noncytopathic strain and cytopathic strain related to the subtyp...

  19. Challenging behaviour: a challenge to change.

    Science.gov (United States)

    van Berckelaer-Onnes, I A; van Loon, J; Peelen, A

    2002-09-01

    People with intellectual disability often exhibit severe behavioural problems. Treatment of these problems is frequently very difficult. In The Netherlands, parents, institutes, schools and others can request the services of an independent advisory team with a pool of professionals who have experience with individuals who exhibit challenging behaviour. In this article the methods of the team will be described using a 24-year-old man as an example. The process took almost 7 years. Finally, this man, who had been living full time in one room in total isolation from the rest of the world, fulfilled his heart's desire--visiting the UK by Hovercraft. PMID:12212917

  20. Nanodelivery System for Mitochondrial Targeting

    Science.gov (United States)

    Yoong, Sia Lee; Pastorin, Giorgia

    2014-02-01

    Mitochondria are indispensable in cellular functions such as energy production and death execution. They are emerging as intriguing therapeutic target as their dysregulation was found to be monumental in diseases such as neurodegenerative disease, obesity, and cancer etc. Despite tremendous interest being focused on therapeutically intervening mitochondrial function, few mito-active drugs were successfully developed, particularly due to challenges in delivering active compound to this organelle. In this review, effort in utilizing nanotechnology for targeted mitochondrial delivery of compound is expounded based on the nature of the nanomaterial used. The advantage and potential offered are discussed alongside the limitation. Finally the review is concluded with perspectives of the application of nanocarrier in mitochondrial medicine, given the unresolved concern on potential complications.

  1. Community Challenge Grantees

    Data.gov (United States)

    Department of Housing and Urban Development — HUD's Community Challenge Grants aim to reform and reduce barriers to achieving affordable, economically vital and sustainable communities. The funds are awarded to...

  2. Brazil World Cup Challenges

    OpenAIRE

    MANSUR, R.

    2012-01-01

    Overcoming the productivity challenge is the main benefit of the 2014 World Cup for Brazilian people. The sustainable development of our cultural tourism industry will catapult the new middle class growing up rate.

  3. Better Buildings Challenge Overview

    Energy Technology Data Exchange (ETDEWEB)

    None

    2011-06-01

    The Better Buildings Challenge is a national leadership initiative calling on corporate chief executive officers, university presidents, and state and local leaders to make a significant commitment to building energy efficiency.

  4. Challenging Fieldwork Situations

    DEFF Research Database (Denmark)

    Bille, Thomas; Østergaard Steenfeldt, Vibeke

    2013-01-01

    understanding on the phenomenon of awkwardness as a natural way for researchers to respond to challenging fieldwork situations. Finally, they propose and unfold mutual interviewing and cooperative analysis as methods of investigating researcher’s subjectivity in facing such situations....

  5. The Electric Car Challenge.

    Science.gov (United States)

    Diehl, Brian E.

    1997-01-01

    Describes the Electric Car Challenge during which students applied methods of construction to build lightweight, strong vehicles that were powered by electricity. The activity required problem solving, sheet metal work, electricity, design, and construction skills. (JOW)

  6. A challenging read

    Directory of Open Access Journals (Sweden)

    Cathy Foley

    2004-11-01

    Full Text Available Andrei Mourachkine uses his new book to argue that superconductivity could be achieved at room temperature and, while his thesis may rest on some unconfirmed evidence, it does challenge preconceptions, says Cathy Foley.

  7. Brazil World Cup Challenges

    Directory of Open Access Journals (Sweden)

    MANSUR, R.

    2012-12-01

    Full Text Available Overcoming the productivity challenge is the main benefit of the 2014 World Cup for Brazilian people. The sustainable development of our cultural tourism industry will catapult the new middle class growing up rate.

  8. Challenges in marine instrumentation

    Digital Repository Service at National Institute of Oceanography (India)

    Afzulpurkar, S.; Desa, E.; Joseph, A.; Chakraborty, B.; Nayak, M.R.; Ranade, G.

    challenge for technology. Biosensors which can detect bioluminescence and other biological activities would play a major role. Autonomous instrumentation outfitted with different types of in-situ sensors would collect data without disturbing the system...

  9. Pandemic Influenza Vaccines – The Challenges

    Directory of Open Access Journals (Sweden)

    Rebecca Cox

    2009-12-01

    Full Text Available Recent years’ enzootic spread of highly pathogenic H5N1 virus among poultry and the many lethal zoonoses in its wake has stimulated basic and applied pandemic vaccine research. The quest for an efficacious, affordable and timely accessible pandemic vaccine has been high on the agenda. When a variant H1N1 strain of swine origin emerged as a pandemic virus, it surprised many, as this subtype is well-known to man as a seasonal virus. This review will cover some difficult vaccine questions, such as the immunological challenges, the new production platforms, and the limited supply and global equity issues.

  10. Managing neurocysticercosis: challenges and solutions.

    Science.gov (United States)

    Fogang, Yannick Fogoum; Savadogo, Abdoul Aziz; Camara, Massaman; Toffa, Dènahin Hinnoutondji; Basse, Anna; Sow, Adjaratou Djeynabou; Ndiaye, Mouhamadou Mansour

    2015-01-01

    Taenia solium neurocysticercosis (NCC) is a major cause of neurological morbidity in the world. Variability in the neuropathology and clinical presentation of NCC often make it difficult to diagnose and manage. Diagnosis of NCC can be challenging especially in endemic and resource-limited countries where laboratory and imaging techniques are often lacking. NCC management can also be challenging as current treatment options are limited and involve symptomatic agents, antiparasitic agents, or surgery. Although antiparasitic treatment probably reduces the number of active lesions and long-term seizure frequency, its efficacy is limited and strategies to improve treatment regimens are warranted. Treatment decisions should be individualized in relation to the type of NCC. Initial measures should focus on symptomatic management, with antiparasitic therapy only to be considered later on, when appropriate. Symptomatic treatment remains the cornerstone in NCC management which should not only focuses on epilepsy, but also on other manifestations that cause considerable burden (recurrent headaches, cognitive decline). Accurate patients' categorization, better antiparasitic regimens, and definition of new clinical outcomes for trials on NCC could improve management quality and prognosis of NCC. Prevention strategies targeting tapeworm carriers and infected pigs are yielding good results in local models. If local elimination of transmission is confirmed and replicated, this will open the door to cysticercosis eradication efforts worldwide. PMID:26527895

  11. Big Data Challenges

    OpenAIRE

    Alexandru Adrian TOLE

    2013-01-01

    The amount of data that is traveling across the internet today, not only that is large, but is complex as well. Companies, institutions, healthcare system etc., all of them use piles of data which are further used for creating reports in order to ensure continuity regarding the services that they have to offer. The process behind the results that these entities requests represents a challenge for software developers and companies that provide IT infrastructure. The challenge is how to manipul...

  12. Anthropocene Age Wicked Challenges

    DEFF Research Database (Denmark)

    Edgeman, Rick; Wu, Zhaohui

    2015-01-01

    weather events, drought, and desertification; threatened food supplies; water pollution, air pollution, and soil contamination; and the connection of these to disease, violence, and terrorism. Wicked challenges are discussed in relation to enterprise excellence, sustainability, resilience and robustness......Grand global challenges, including wicked human caused or influenced ones key to sustainability, characterize the Anthropocene Age. Among these are climate change driven by increased methane and CO2 in the atmosphere; consequent global warming and increasing intensity and incidence of extreme...

  13. Challenges in obesity research

    OpenAIRE

    Andreu Palou; Luisa Bonet, M.

    2013-01-01

    Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors -often interrelated and many of them still unknown or poorly understood- can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regard...

  14. Overcoming Safeguards Challenges

    International Nuclear Information System (INIS)

    The focus of the 2010 IAEA International Safeguards Symposium was how best, from a technical perspective, to prepare for future verification challenges during this time of change. By bringing together the leading experts in the field from across the world, this symposium provided an opportunity for stakeholders to explore possible solutions in support of the IAEA's nuclear verification mission, and to identify areas where the different stakeholders in the safeguards business can help address these challenges

  15. Optimal challenges in tennis

    OpenAIRE

    Clarke, S. R.; Norman, J.M.

    2012-01-01

    The use of technology in sport to assist umpires has been gradually introduced into several sports. This has now been extended to allow players to call upon technology to arbitrate when they disagree with the umpire's decision. Both tennis and cricket now allow the players to challenge a doubtful decision, which is reversed if the evidence shows it to be incorrect. However, the number of challenges is limited, and players must balance any possible immediate gain with the loss of a future righ...

  16. TL transgenic mouse strains

    International Nuclear Information System (INIS)

    As a result of abnormal development of the thymus of these mice, TCR αβ lineage of the T cell differentiation is disturbed and cells belonging to the TCR γδ CD4- CD8- double negative (DN) lineage become preponderant. The γδ DN cells migrate into peripheral lymphoid organs and constitute nearly 50% of peripheral T cells. Immune function of the transgenic mice is severely impaired, indicating that the γδ cells are incapable of participating in these reactions. Molecular and serological analyses of T-cell lymphomas reveal that they belong to the γδ lineage. Tg.Tlaa-3-1 mice should be useful in defining the role of TL in normal and abnormal T cell differentiation as well as in the development of T-cell lymphomas, and further they should facilitate studies on the differentiation and function of γδ T cells. We isolated T3b-TL gene from B6 mice and constructed a chimeric gene in which T3b-TL is driven by the promoter of H-2Kb. With the chimeric gene, two transgenic mouse strains, Tg. Con.3-1 and -2 have been derived in C3H background. Both strains express TL antigen in various tissues including skin. The skin graft of transgenic mice on C3H and (B6 X C3H)F1 mice were rejected. In the mice which rejected the grafts, CD8+TCRαβ cytotoxic T cells (CTL) against TL antigens were recognized. The recognition of TL by CTL did not require the antigen presentation by H-2 molecules. The results indicated that TL antigen in the skin becomes a transplantation antigen and behaves like a typical allogeneic MHC class I antigen. The facts that (B6 X C3H)F1 mice rejected the skin expressing T3b-TL antigen and induced CTL that killed TL+ lymphomas of B6 origin revealed that TL antigen encoded by T3b-TL is recognized as non-self in B6 mice. Experiments are now extended to analyze immune responses to TL antigen expressed on autochthonous T cell lymphomas. (J.P.N.)

  17. Evaluation of an attenuated strain of Ehrlichia canis as a vaccine for canine monocytic ehrlichiosis.

    Science.gov (United States)

    Rudoler, Nir; Baneth, Gad; Eyal, Osnat; van Straten, Michael; Harrus, Shimon

    2012-12-17

    Canine monocytic ehrlichiosis is an important tick-borne disease worldwide. No commercial vaccine for the disease is currently available and tick control is the main preventive measure against the disease. The aim of this study was to evaluate the potential of a multi-passaged attenuated strain of Ehrlichia canis to serve as a vaccine for canine monocytic ehrlichiosis, and to assess the use of azithromycin in the treatment of acute ehrlichiosis. Twelve beagle dogs were divided into 3 groups of 4 dogs. Groups 1 and 2 were inoculated (vaccinated) with an attenuated strain of E. canis (#611A) twice or once, respectively. The third group consisted of naïve dogs which served as controls. All 3 groups were challenged with a wild virulent strain of E. canis by administering infected dog-blood intravenously. Transient thrombocytopenia was the only hematological abnormality observed following inoculation of dogs with the attenuated strain. Challenge with the virulent strain resulted in severe disease in all 4 control dogs while only 3 of 8 vaccinated dogs presented mild transient fever. Furthermore, the mean blood rickettsial load was significantly higher in the control group (27-92-folds higher during days 14-19 post challenge with the wild the strain) as compared to the vaccinated dogs. The use of azithromycin was assessed as a therapeutic agent for the acute disease. Four days treatment resulted in further deterioration of the clinical condition of the dogs. Molecular comparison of 4 genes known to express immunoreactive proteins and virulence factors (p30, gp19, VirB4 and VirB9) between the attenuated strain and the challenge wild strain revealed no genetic differences between the strains. The results of this study indicate that the attenuated E. canis strain may serve as an effective and secure future vaccine for canine ehrlichiosis. PMID:23072894

  18. Psychological strains and youth suicide in rural China.

    Science.gov (United States)

    Zhang, Jie; Wieczorek, William F; Conwell, Yeates; Tu, Xin Ming

    2011-06-01

    The strain theory of suicide postulates that suicide is usually preceded by psychological strains. A strain can be a consequence of any of four conflicts: differential values, aspiration and reality, relative deprivation, and lack of coping skills for a crisis. This study, with a blend of psychiatric and social predictors of suicide, identified correlates of suicide that are relevant to Chinese culture and tested the strain theory of suicide with Chinese data. We sampled 392 suicides and 416 living controls (both aged 15-34 years) from 16 rural counties in China in 2008 and interviewed two informants for each suicide and each control. We found that marriage and religion/religiosity did not distinguish the suicides from the living controls among Chinese rural young women. Religion/religiosity tended to be stronger for suicides than for controls. Psychological strains in the forms of relative deprivation, unrealized aspiration, and lack of coping skills were significantly associated with suicide, even after accounting for the role of mental illness. The strain theory of suicide forms a challenge to the psychiatric model popular in the West, at least in explaining the Chinese suicide. PMID:21640457

  19. Strain engineered optoelectronic properties of transition metal dichalcogenides lateral heterostructures

    Science.gov (United States)

    Lee, Jaekwang; Yoon, Mina

    2015-03-01

    Most three-dimensional bulk-scale materials rarely survive beyond 1% strain, while recently spotlighted two-dimensional (2-D) materials can sustain a high elastic strain (up to 10%) to optimize optical quantities such as band gaps and absorption spectra governing optoelectronic device performance. Despite the enormous interest in strained 2-D materials, most researches are focused on single materials or vertical heterostructures where precise control of stacking orientation is challenging. Here, using first-principles density-functional calculations, we explore how uniaxial tensile strains modify overall electronic and optical properties of transition metal dichalcogenides lateral heterostructures, such as MoX2/WX2 (X =S, Se). Based on the detailed optoelectronic information, we predict the optimal strain condition for maximal power efficiency. Furthermore, we find that uniaxial tensile strain readily develops a continuously varying direct-bandgap across the lateral heterojunctions, which results in the broad range absorption of solar spectrum useful for future optoelectronic devices. This research was conducted at the CNMS, which is sponsored at Oak Ridge National Laboratory (ORNL) by the Office of Basic Energy Sciences, U.S. Department of Energy; a portion of theory work was supported by the LDRD Program of ORNL.

  20. Influence of corrosion on the strain profiles of pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Jamieson, G.; Newhook, J.P. [Dalhousie Univ., Halifax, NS (Canada). Dept. of Civil Engineering

    2003-07-01

    Natural gas, oil and petroleum products in Canada are transported by pipelines, many of which are over a quarter of a century old. A major challenge facing the petroleum industry is corrosion of pipelines. To minimize the probability of a line failure, pipeline owners adhere to strict inspection and maintenance schedules. Maintenance, using current in-line inspection tools, necessitates the transmission lines to be shut down. This paper described an alternative way to detect pipeline corrosion, using a numerical investigation of the change in strain profile of a corroded pipeline under internal pressure. A finite element model of a typical thin-walled pressure vessel was created under linear elastic axisymmetric conditions. The thinning of the wall simulated corrosion. The authors studied the change in longitudinal and circumferential strain under the same operating pressure. A parametric study was performed using a wide array of corrosion geometries and depths. A distinct and detectable change in strain for specific degrees of corrosion was identified. An increase in the amount of corrosion resulted in an increase in the rate of circumferential and longitudinal strains. The geometry of the corrosion profile had a big influence on the slope of the strain gradient. According to the initial evaluation, it appears feasible to design a structural health monitoring system using continuous strain monitoring as its basis, but additional studies are required to model actual in-situ pipeline conditions, as well as an assessment of non-linear response. 5 refs., 2 tabs., 7 figs.

  1. Tumor targeting via integrin ligands

    Directory of Open Access Journals (Sweden)

    HorstKessler

    2013-08-01

    Full Text Available Selective and targeted delivery of drugs to tumors is a major challenge for an effective cancer therapy and also to overcome the side effects associated with current treatments. Overexpression of various receptors on tumor cells is a characteristic structural and biochemical aspect of tumors and distinguishes them from physiologically normal cells. This abnormal feature is therefore suitable for selectively directing anticancer molecules to tumors by using ligands that can preferentially recognize such receptors. Several subtypes of integrin receptors that are crucial for cell adhesion, cell signaling, cell viability and motility have been shown to have an upregulated expression on cancer cells. Thus, ligands that recognize specific integrin subtypes represent excellent candidates to be conjugated to drugs or drug carrier systems and be targeted to tumors. In this regard, integrins recognizing the RGD cell adhesive sequence have been extensively targeted for tumor specific drug delivery. Here we review key recent examples on the presentation of RGD-based integrin ligands by means of distinct drug delivery systems, and discuss the prospects of such therapies to specifically target tumor cells.

  2. Non-targeted effects of ionising radiation

    International Nuclear Information System (INIS)

    The universality of the target theory of radiation-induced effects is challenged by observations on non-targeted effects such as bystander effects and genomic instability. Essential features of non-targeted effects are that they do not require direct nuclear exposure by radiation and they are particularly significant at low doses. This new evidence suggests a need for a new paradigm in radiation biology. The new paradigm would cover both the classical (targeted) and the non-targeted effects. New aspects include the role of cellular communication and tissue-level responses. A better understanding of non-targeted effects may have important consequences for health risk assessment and, consequently, on radiation protection. Non-targeted effects may contribute to the estimation of cancer risk from occupational, medical and environmental exposures. In particular, they may have implications for the applicability of the Linear-No-Threshold (LNT) model in extrapolating radiation risk data into the low-dose region. This also means that the adequacy of the concept of dose to estimate risk is challenged by these findings. Moreover, these effects may provide new mechanistic explanations for the development of non-cancer diseases. Further research is required to determine if these effects, typically measured in cell cultures, are applicable in tissue level, whole animals, and ultimately in humans. (orig.)

  3. What Are Sprains and Strains?

    Science.gov (United States)

    ... and Strains Find a Clinical Trial Journal Articles Sprains and Strains PDF Version Size: 119 KB Audio Version Time: 07: ... Twist a knee. Where Do Sprains Usually Occur? Sprains happen most often in the ankle. Sometimes when people fall and land on their ...

  4. Quantitative targeting maps based on experimental investigations for a branched tube model in magnetic drug targeting

    Energy Technology Data Exchange (ETDEWEB)

    Gitter, K., E-mail: kurt.gitter@tu-dresden.de [TU Dresden, Institute of Fluid Mechanics, Chair of Magnetofluiddynamics, 01062 Dresden (Germany); Odenbach, S. [TU Dresden, Institute of Fluid Mechanics, Chair of Magnetofluiddynamics, 01062 Dresden (Germany)

    2011-12-15

    Magnetic drug targeting (MDT), because of its high targeting efficiency, is a promising approach for tumour treatment. Unwanted side effects are considerably reduced, since the nanoparticles are concentrated within the target region due to the influence of a magnetic field. Nevertheless, understanding the transport phenomena of nanoparticles in an artery system is still challenging. This work presents experimental results for a branched tube model. Quantitative results describe, for example, the net amount of nanoparticles that are targeted towards the chosen region due to the influence of a magnetic field. As a result of measurements, novel drug targeting maps, combining, e.g. the magnetic volume force, the position of the magnet and the net amount of targeted nanoparticles, are presented. The targeting maps are valuable for evaluation and comparison of setups and are also helpful for the design and the optimisation of a magnet system with an appropriate strength and distribution of the field gradient. The maps indicate the danger of accretion within the tube and also show the promising result of magnetic drug targeting that up to 97% of the nanoparticles were successfully targeted. - Highlights: > Quantitative targeting maps summarise a series of measurements. > Targeting maps combine quantitative data, magnetic volume forces and magnet position. > Here, up to 97% of injected particles were targeted towards the tumour region. > High concentration of injected ferrofluid brings the danger of accretion. > Low miscibility of ferrofluid by water modelling the blood flow is detected.

  5. Tuberculosis diagnostics: Challenges and opportunities

    Directory of Open Access Journals (Sweden)

    Vijay Nema

    2012-01-01

    Full Text Available Tuberculosis (TB has been a disease affecting almost all parts of the world since ages. Lot many efforts came in the past for improving diagnosis and treatment. Also, an effective vaccine has been sought after for long. With the emergence of resistant strains of Mycobacterium tuberculosis, the causal organisms of tuberculosis, and complexities emerging due to other associated infections and disease conditions, there is a desperate need for further research input in the field. Be it the better medication and care or better resistance management, proper diagnostics holds the key to success. It has been observed that a high burden of the disease was accompanied by resource limitations and poor research set-up. The scenario remained like this for several decades. With the refreshed vision of resourceful countries and funding agencies, funding is being provided in many areas of research in tuberculosis diagnosis and treatment. This review has been written with an aim to bring forth the limitations of available methods in the field of diagnostics and making researchers aware about the changing scenario with better funding opportunities and support. The author visualizes an enthusiasm from all over the world for the development of better modalities and urges scientists to join the struggle at this very perfect time to take the challenge and come forward with innovations in this field.

  6. Silicon spintronics: Progress and challenges

    Energy Technology Data Exchange (ETDEWEB)

    Sverdlov, Viktor; Selberherr, Siegfried, E-mail: Selberherr@TUWien.ac.at

    2015-07-14

    Electron spin attracts much attention as an alternative to the electron charge degree of freedom for low-power reprogrammable logic and non-volatile memory applications. Silicon appears to be the perfect material for spin-driven applications. Recent progress and challenges regarding spin-based devices are reviewed. An order of magnitude enhancement of the electron spin lifetime in silicon thin films by shear strain is predicted and its impact on spin transport in SpinFETs is discussed. A relatively weak coupling between spin and effective electric field in silicon allows magnetoresistance modulation at room temperature, however, for long channel lengths. Due to tunneling magnetoresistance and spin transfer torque effects, a much stronger coupling between the spin (magnetization) orientation and charge current is achieved in magnetic tunnel junctions. Magnetic random access memory (MRAM) built on magnetic tunnel junctions is CMOS compatible and possesses all properties needed for future universal memory. Designs of spin-based non-volatile MRAM cells are presented. By means of micromagnetic simulations it is demonstrated that a substantial reduction of the switching time can be achieved. Finally, it is shown that any two arbitrary memory cells from an MRAM array can be used to perform a logic operation. Thus, an intrinsic non-volatile logic-in-memory architecture can be realized.

  7. Silicon spintronics: Progress and challenges

    International Nuclear Information System (INIS)

    Electron spin attracts much attention as an alternative to the electron charge degree of freedom for low-power reprogrammable logic and non-volatile memory applications. Silicon appears to be the perfect material for spin-driven applications. Recent progress and challenges regarding spin-based devices are reviewed. An order of magnitude enhancement of the electron spin lifetime in silicon thin films by shear strain is predicted and its impact on spin transport in SpinFETs is discussed. A relatively weak coupling between spin and effective electric field in silicon allows magnetoresistance modulation at room temperature, however, for long channel lengths. Due to tunneling magnetoresistance and spin transfer torque effects, a much stronger coupling between the spin (magnetization) orientation and charge current is achieved in magnetic tunnel junctions. Magnetic random access memory (MRAM) built on magnetic tunnel junctions is CMOS compatible and possesses all properties needed for future universal memory. Designs of spin-based non-volatile MRAM cells are presented. By means of micromagnetic simulations it is demonstrated that a substantial reduction of the switching time can be achieved. Finally, it is shown that any two arbitrary memory cells from an MRAM array can be used to perform a logic operation. Thus, an intrinsic non-volatile logic-in-memory architecture can be realized

  8. Performance Targets and External Market Prices

    DEFF Research Database (Denmark)

    Hansen, Allan; Friis, Ivar; Vámosi, Tamás S.

    In this paper we explore the processes of ‘bringing the market inside the firm’ to set performance targets and benchmark production workers productivity. We analyze attempts to use external suppliers’ bids in target setting in a Danish manufacturing company. The case study illustrates how the...... implementation of external market information in target setting – well known in transfer pricing, relative performance evaluation, beyond budgeting, target costing, piece rates systems and value based management – relate to challenging motivation and information problem. The analysis and discussion of those...... problems, in particular those related to accounting for the internal performance (that are going to be compared with the external target), calculating the ‘inside’ costs and defining controllability, contributes to the management accounting as well as the piece-rate literature....

  9. Strain measurements at railway wheels

    International Nuclear Information System (INIS)

    The development of the radial strain component in railway wheels was investigated by neutron diffraction. In the as manufactured state four railway wheels were investigated. In all four wheels no significant strains were found. After 18,400 km usage first strain gradients close to the outer surface of the wheels were detected. In axial middle ranges the changes in strain are weak. After an usage of 61,000 km the gradients becomes strong at the axial outer position between about +700 με close below the tread and -500 με in a depth of 12.5 mm below the tread. At axial middle positions also strain gradients are formed. The end of live state (510,000 km) differs only slightly from the state measured after a usage of 61,000 km

  10. Genome assembly reborn: recent computational challenges

    OpenAIRE

    Pop, Mihai

    2009-01-01

    Research into genome assembly algorithms has experienced a resurgence due to new challenges created by the development of next generation sequencing technologies. Several genome assemblers have been published in recent years specifically targeted at the new sequence data; however, the ever-changing technological landscape leads to the need for continued research. In addition, the low cost of next generation sequencing data has led to an increased use of sequencing in new settings. For example...

  11. Genital immunization of heifers with a glycoprotein Edeleted, recombinant bovine herpesvirus 1 strain confers protection upon challenge with a virulent isolate Imunização genital de bezerras com uma cepa recombinante do herpesvírus bovino tipo 1 defectiva na glicoproteína E confere proteção frente a desafio com um isolado virulento

    OpenAIRE

    Marcelo Weiss; Fernanda S.F. Vogel; Mathias Martins; Rudi Weiblen; Paulo M Roehe; Ana Cláudia Franco; Eduardo Furtado Flores

    2010-01-01

    Venereal infection of seronegative heifers and cows with bovine herpesvirus type 1.2 (BoHV-1.2) frequently results in vulvovaginitis and transient infertility. Parenteral immunization with inactivated or modified live BoHV-1 vaccines often fails in conferring protection upon genital challenge. We herein report an evaluation of the immune response and protection conferred by genital vaccination of heifers with a glycoprotein E-deleted recombinant virus (SV265gE-). A group of six seronegative h...

  12. Cognitive Radio RF: Overview and Challenges

    Directory of Open Access Journals (Sweden)

    Van Tam Nguyen

    2012-01-01

    Full Text Available Cognitive radio system (CRS is a radio system which is aware of its operational and geographical environment, established policies, and its internal state. It is able to dynamically and autonomously adapt its operational parameters and protocols and to learn from its previous experience. Based on software-defined radio (SDR, CRS provides additional flexibility and offers improved efficiency to overall spectrum use. CRS is a disruptive technology targeting very high spectral efficiency. This paper presents an overview and challenges of CRS with focus on radio frequency (RF section. We summarize the status of the related regulation and standardization activities which are very important for the success of any emerging technology. We point out some key research challenges, especially implementation challenges of cognitive radio (CR. A particular focus is on RF front-end, transceiver, and analog-to-digital and digital-to-analog interfaces which are still a key bottleneck in CRS development.

  13. Recent advances in echocardiography: strain and strain rate imaging

    Science.gov (United States)

    Mirea, Oana; Duchenne, Jurgen; Voigt, Jens-Uwe

    2016-01-01

    Deformation imaging by echocardiography is a well-established research tool which has been gaining interest from clinical cardiologists since the introduction of speckle tracking. Post-processing of echo images to analyze deformation has become readily available at the fingertips of the user. New parameters such as global longitudinal strain have been shown to provide added diagnostic value, and ongoing efforts of the imaging societies and industry aimed at harmonizing methods will improve the technique further. This review focuses on recent advances in the field of echocardiographic strain and strain rate imaging, and provides an overview on its current and potential future clinical applications.

  14. Hydration and thermal strain during tennis in the heat

    Science.gov (United States)

    Bergeron, Michael F

    2014-01-01

    Competitive tennis in the heat can prompt substantial sweat losses and extensive consequent body water and electrolyte deficits, as well as a level of thermal strain that considerably challenges a player's physiology, perception of effort, and on-court well-being and performance. Adequate hydration and optimal performance can be notably difficult to maintain when multiple same-day matches are played on successive days in hot weather. Despite the recognised effects of the heat, much more research needs to be carried out to better appreciate the broader scope and full extent of the physiological demands and hydration and thermal strain challenges facing junior and adult players in various environments, venues and competition scenarios. However, certain recommendations of best practices should be emphasised to minimise exertional heat illness risk and improve player safety, well-being and on-court performance. PMID:24668373

  15. Bacteriophage-Derived Vectors for Targeted Cancer Gene Therapy

    OpenAIRE

    Md Zahidul Islam Pranjol; Amin Hajitou

    2015-01-01

    Cancer gene therapy expanded and reached its pinnacle in research in the last decade. Both viral and non-viral vectors have entered clinical trials, and significant successes have been achieved. However, a systemic administration of a vector, illustrating safe, efficient, and targeted gene delivery to solid tumors has proven to be a major challenge. In this review, we summarize the current progress and challenges in the targeted gene therapy of cancer. Moreover, we highlight the recent dev...

  16. Electrospun Fibrous Membranes with Super-large-strain Electric Superhydrophobicity

    Science.gov (United States)

    Zhou, Hua; Wang, Hongxia; Niu, Haitao; Lin, Tong

    2015-10-01

    Large-strain elastic superhydrophobicity is highly desirable for its enhanced use performance and functional reliability in mechanically dynamic environments, but remains challenging to develop. Here we have, for the first time, proven that an elastic fibrous membrane after surface hydrophobization can maintain superhydrophobicity during one-directional (uniaxial) stretching to a strain as high as 1500% and two-direction (biaxial) stretching to a strain up to 700%. The fibrous membrane can withstand at least 1,000 cycles of repeated stretching without losing the superhydrophobicity. Stretching slightly increases the membrane air permeability and reduces water breakthrough pressure. It is highly stable in acid and base environments. Such a permeable, highly-elastic superhydrophobic membrane may open up novel applications in membrane separation, healthcare, functional textile and energy fields.

  17. Newcastle disease in white Pekin ducks: response to experimental vaccination and challenge

    OpenAIRE

    Nishizawa, M; AC Paulillo; LSO Nakaghi; AD Nunes; JM Campioni; L Doretto Júnior

    2007-01-01

    A total of 120 Pekin ducks were distributed at random into four experimental groups, vaccinated or not against Newcastle disease (ND): G1 (Ulster 2C strain), G2 (B1 strain), G3 (LaSota strain), and G4 (nonvaccinated group). At 60 days of age, all groups were challenged with a pathogenic ND virus (NDV) suspension, and a group of specific pathogen free (SPF) chicks (G5) was also inoculated. Cloacal and tracheal swabs from all birds were collected after six, 14, 20, and 30 days post-challenge fo...

  18. Prevention of Clostridium difficile infection in hamsters using a non-toxigenic strain

    Directory of Open Access Journals (Sweden)

    Carlos Augusto de Oliveira Júnior

    2016-05-01

    Full Text Available ABSTRACT: The present study aimed to evaluate five non-toxigenic strains of Clostridium difficile (NTCD in vitro and to select one strain to prevent C. difficile (CDI infection in hamsters ( Mesocricetus auratus . The NTCD strains were evaluated for spore production in vitro, antimicrobial susceptibility and presence of antimicrobial resistance genes. Approximately 107 spores of the selected strain (Z31 were administered by esophageal gavage in hamsters pretreated with 30mg kg-1 of clindamycin. The challenge with a toxigenic strain of C. difficile was conducted at 36 and 72h, and the animals were observed for 28 days. The NTCD strain of C. difficile (Z31 was able to prevent CDI in all animals that received it.

  19. Hamstring Strain Injuries: Recommendations for Diagnosis, Rehabilitation and Injury Prevention

    OpenAIRE

    Heiderscheit, Bryan C.; Sherry, Marc A.; Silder, Amy; Chumanov, Elizabeth S.; Thelen, Darryl G.

    2010-01-01

    Hamstring strain injuries remain a challenge for both athletes and clinicians given the high incidence rate, slow healing, and persistent symptoms. Moreover, nearly one-third of these injuries recur within the first year following a return to sport, with subsequent injuries often being more severe than the original. This high reinjury rate suggests that commonly utilized rehabilitation programs may be inadequate at resolving possible muscular weakness, reduced tissue extensibility, and/or alt...

  20. Improving industrial yeast strains: exploiting natural and artificial diversity

    OpenAIRE

    Steensels, Jan; Snoek, Tim; Meersman, Esther; Nicolino, Martina Picca; Voordeckers, Karin; Verstrepen, Kevin J.

    2014-01-01

    Yeasts have been used for thousands of years to make fermented foods and beverages, such as beer, wine, sake, and bread. However, the choice for a particular yeast strain or species for a specific industrial application is often based on historical, rather than scientific grounds. Moreover, new biotechnological yeast applications, such as the production of second-generation biofuels, confront yeast with environments and challenges that differ from those encountered in traditional food ferment...

  1. Hydration and thermal strain during tennis in the heat

    OpenAIRE

    Bergeron, Michael F.

    2014-01-01

    Competitive tennis in the heat can prompt substantial sweat losses and extensive consequent body water and electrolyte deficits, as well as a level of thermal strain that considerably challenges a player's physiology, perception of effort, and on-court well-being and performance. Adequate hydration and optimal performance can be notably difficult to maintain when multiple same-day matches are played on successive days in hot weather. Despite the recognised effects of the heat, much more resea...

  2. The potent enhancer activity of the polycythemic strain of spleen focus-forming virus in hematopoietic cells is governed by a binding site for Sp1 in the upstream control region and by a unique enhancer core motif, creating an exclusive target for PEBP/CBF.

    OpenAIRE

    Baum, C; Itoh, K; DE MEYER, J; Laker, C; Ito, Y.; Ostertag, W

    1997-01-01

    The polycythemic strain of the spleen focus-forming virus (SFFVp) contains the most potent murine retroviral enhancer configuration known so far for gene expression in myeloerythroid hematopoietic cells. In the present study, we mapped two crucial elements responsible for the high activity of the SFFVp enhancer to an altered upstream control region (UCR) containing a GC-rich motif (5'-GGGCGGG-3') and to a unique enhancer core (5'-TGCGGTC-3'). Acquisition of these motifs accounts for half of t...

  3. A duplex PCR assay for the detection of Ralstonia solanacearum phylotype II strains in Musa spp.

    Science.gov (United States)

    Cellier, Gilles; Moreau, Aurélie; Chabirand, Aude; Hostachy, Bruno; Ailloud, Florent; Prior, Philippe

    2015-01-01

    Banana wilt outbreaks that are attributable to Moko disease-causing strains of the pathogen Ralstonia solanacearum (Rs) remain a social and economic burden for both multinational corporations and subsistence farmers. All known Moko strains belong to the phylotype II lineage, which has been previously recognized for its broad genetic basis. Moko strains are paraphyletic and are distributed among seven related but distinct phylogenetic clusters (sequevars) that are potentially major threats to Musaceae, Solanaceae, and ornamental crops in many countries. Although clustered within the Moko IIB-4 sequevar, strains of the epidemiologically variant IIB-4NPB do not cause wilt on Cavendish or plantain bananas; instead, they establish a latent infection in the vascular tissues of plantains and demonstrate an expanded host range and high aggressiveness toward Solanaceae and Cucurbitaceae. Although most molecular diagnostic methods focus on strains that wilt Solanaceae (particularly potato), no relevant protocol has been described that universally detects strains of the Musaceae-infecting Rs phylotype II. Thus, a duplex PCR assay targeting Moko and IIB-4NPB variant strains was developed, and its performance was assessed using an extensive collection of 111 strains representing the known diversity of Rs Moko-related strains and IIB-4NPB variant strains along with certain related strains and families. The proposed diagnostic protocol demonstrated both high accuracy (inclusivity and exclusivity) and high repeatability, detected targets on either pure culture or spiked plant extracts. Although they did not belong to the Moko clusters described at the time of the study, recently discovered banana-infecting strains from Brazil were also detected. According to our comprehensive evaluation, this duplex PCR assay appears suitable for both research and diagnostic laboratories and provides reliable detection of phylotype II Rs strains that infect Musaceae. PMID:25811378

  4. The challenge of sustainability

    International Nuclear Information System (INIS)

    This paper discusses sustainability in a world that has changed rapidly. The author suggests that ecological assumptions embedded in communism and capitalism are badly flawed, but the flaws were not apparent when there were fewer than a billion people on earth living at low technology levels. Sustaining the earth's vital signs is a challenge to our perception of time, and the numbers - population, environmental damage, oil consumption, waste disposal - are too large to comprehend easily. There is a global debate about what sustainability means. In fact the challenge of sustainability is 6 different challenges: overcoming the tendency to deny inconvenient realities; establishing accurate indicators of human and ecological health; questions about the kinds of technology necessary to make the transition to sustainability; education; the need for an emotional bond between man and nature; rebuilding the existing democratic institutions. 16 refs

  5. Meeting the Challenge

    Directory of Open Access Journals (Sweden)

    T. Reg Bott

    2009-01-01

    Full Text Available The first Chempor Conference held in Lisbon in 1975 under the auspices of the Calouste Gulbenkian Foundation, heralded a regular wide-ranging review of research and development in Portugal and the UK Progressively in later years the Conferences have attracted contributions from other European countries and indeed further afield. There is an increasing awareness of the problems for the environment, notably global warming, brought about by human activities. Recent predictions about the future are dire, particularly regarding food and water for a rapidly growing world population. They represent a substantial challenge to the scientific and technical fraternity. In response to that challenge it is important to keep up to date with technical developments, to meet and keep in touch with coworkers in associated fields, and to cooperate wherever possible. The papers presented at the Chempor and other conferences have made and continue to make a significant contribution to that objective of meeting the challenge.

  6. Experimental Infection of Richardson's Ground Squirrels (Spermophilus richardsonii) with Attenuated and Virulent Strains of Brucella abortus

    Science.gov (United States)

    Exposure of non-target species to wildlife vaccines is an important concern when evaluating a candidate vaccine for use in the field. A previous investigation of the safety of Brucella abortus strain RB51 (sRB51) in various non-target species suggested that Richardson’s ground squirrels (Spermophil...

  7. Effective neutron targets

    International Nuclear Information System (INIS)

    Because of the lack of a free neutron target, deuterium targets have been used extensively in studying the neutron structure. The unique spin structure of the 3He ground state wave function and the recent developments in laser technologies made polarized 3He targets widely used in many experiments from neutron electromagnetic form factor studies to nucleon spin structure function measurements at all major electron accelerator facilities. In this talk, the current status of the polarized 3He targets will be reviewed. The author will focus on neutron electromagnetic form factor studies using polarized 3He targets. The polarized nucleon spin structure function measurements using polarized 3He targets will also be discussed

  8. Magnetostriction strain measurement: heterodyne laser interferometry versus strain gauge technique

    OpenAIRE

    Gorji Ghalamestani, Setareh; Vandevelde, Lieven; J.J. Dirckx, Joris; Melkebeek, Jan

    2013-01-01

    Deformation of the ferromagnetic material, known as magnetostriction, causes vibrations and noise of electrical machines and transformer cores. A setup by using heterodyne laser interferometers has been built to measure the magnetostriction strains as a function of the applied magnetic field. The measurement results on a sample of nonoriented electrical steel are presented in this work. These results are compared with those obtained by using a strain gauge setup. The laser measurements are l...

  9. Mercury retention in several strains and strain crosses of chickens

    Energy Technology Data Exchange (ETDEWEB)

    Miller, V.L.; Bearse, G.E.; Csonka, E.

    1970-01-01

    The retention of mercury from injections of mercuric chloride was determined in 32 samples of chicks from various strains and strain crosses of egg type stock. The chicks retaining the most mercury had some four times as much mercury in the liver and kidneys as the chicks retaining the lowest amount. The chicks selected for resistance to leukosis retained more mercury than the susceptible chicks within several leukosis breeding programs.

  10. Low TCR nanocomposite strain gages

    Science.gov (United States)

    Gregory, Otto J. (Inventor); Chen, Ximing (Inventor)

    2012-01-01

    A high temperature thin film strain gage sensor capable of functioning at temperatures above 1400.degree. C. The sensor contains a substrate, a nanocomposite film comprised of an indium tin oxide alloy, zinc oxide doped with alumina or other oxide semiconductor and a refractory metal selected from the group consisting of Pt, Pd, Rh, Ni, W, Ir, NiCrAlY and NiCoCrAlY deposited onto the substrate to form an active strain element. The strain element being responsive to an applied force.

  11. British Muslims: A Challenge

    OpenAIRE

    Abdel-Hady, Zakaryya Mohamed [زكريا محمد عبد الهادي

    2007-01-01

    The Muslim community in Britain today face multiple challenges covering a wide range of spectrum from the basic right to exists, fighting the increasing trends of Islamophobia, having equal opportunities, to participate in public life, fully integrate within the society and be a positive member of the community. The recent events of September 11th in the US, July 7th in UK and the more recent row over the ban of the headscarf in UK and other European countries have placed tremendous challenge...

  12. Banff Challenge 2

    CERN Document Server

    Junk, Thomas R

    2011-01-01

    Experimental particle physics collaborations constantly seek newer and better ideas for improving the sensitivity of their searches for new particles and phenomena. Statistical techniques are the last step in interpreting the results of an experiment; they are used to make discoveries (hypothesis testing), and to measure parameters (point estimation). They are also used in the first step - experiment and analysis design. Banff Challenge 2 asks participants to test their methods of disco vering hidden signals in simulated datasets and of measuring the properties of these signals. The Challenge problems are described, and the performances of the submitted entries is summarized, for datasets with and without simulated signals present.

  13. Challenges facing production grids

    Energy Technology Data Exchange (ETDEWEB)

    Pordes, Ruth; /Fermilab

    2007-06-01

    Today's global communities of users expect quality of service from distributed Grid systems equivalent to that their local data centers. This must be coupled to ubiquitous access to the ensemble of processing and storage resources across multiple Grid infrastructures. We are still facing significant challenges in meeting these expectations, especially in the underlying security, a sustainable and successful economic model, and smoothing the boundaries between administrative and technical domains. Using the Open Science Grid as an example, I examine the status and challenges of Grids operating in production today.

  14. The challenge of conceiving

    DEFF Research Database (Denmark)

    Hansen, Claus Thorp; Jørgensen, Ulrik

    2011-01-01

    One of the big challenges in the CDIO approach to engineering education is the first part focusing on conceiving problems to be handled and eventually solved. Traditional engineering education has been dominated by its focus on technical disciplines emphasising their individual tool box of problem...... problem from the perspective of engineering design challenges where the need for problem identification is obvious to avoid the pitfall to reproduce and piecemeal engineer already existing product or service concepts. Problem identification is not a simple desk research task as it often involves a...

  15. Molecular Targets for Targeted Radionuclide Therapy

    International Nuclear Information System (INIS)

    Molecular targeted radionuclide cancer therapy is becoming of increasing importance, especially for disseminated diseases. Systemic chemotherapies often lack selectivity while targeted radionuclide therapy has important advantages as the radioactive cytotoxic unit of the targeting vector is specifically directed to the cancer, sparing normal tissues. The principle strategy to improve cancer selectivity is to couple therapeutic agents to tumour-targeting vectors. In targeted radionuclide therapy (TRT), the cytotoxic portion of the conjugates normally contains a therapeutic radiometal immobilised by a bifunctional chelator. The aim is therefore to use as ligand-targeted therapeutics vectors coupled to Auger-, alpha- and/or beta-emitting radionuclides. An advantage of using radiation instead of chemotherapeutics as the cytotoxic agent is the so called 'crossfire effect'. This allows sterilisation of tumour cells that are not directly targeted due to heterogeneity in target molecule expression or inhomogeneous vector delivery. However, before the targeting ligands can be selected, the target molecule on the tumour has to be selected. It should be uniquely expressed, or at least highly overexpressed, on or in the target cells relative to normal tissues. The target should be easily accessible for ligand delivery and should not be shed or down- regulated after ligand binding. An important property of a receptor (or antigen) is its potential to be internalized upon binding of the ligand. This provides an active uptake mechanism and allows the therapeutic agent to be trapped within the tumour cells. Molecular targets of current interest include: Receptors: G-protein coupled receptors are overexpressed on many major human tumours. The prototype of these receptors are somatostatin receptors which show very high density in neuroendocrine tumours, but there are many other most interesting receptors to be applied for TRT. The targeting ligands for these receptors are

  16. 76 FR 56819 - Centennial Challenges 2012 Sample Return Robot Challenge

    Science.gov (United States)

    2011-09-14

    ... SPACE ADMINISTRATION Centennial Challenges 2012 Sample Return Robot Challenge AGENCY: National... 42 U.S.C. 2451(314)(d). The 2012 Sample Return Robot Challenge is scheduled and teams that wish to... technologies of interest and value to NASA and the nation. The 2012 Sample Return Robot Challenge is a...

  17. 77 FR 70835 - Centennial Challenges 2013 Sample Return Robot Challenge

    Science.gov (United States)

    2012-11-27

    ... SPACE ADMINISTRATION Centennial Challenges 2013 Sample Return Robot Challenge AGENCY: National... in accordance with 51 U.S.C. 20144(c). The 2013 Sample Return Robot Challenge is scheduled and teams... Robot Challenge is a prize competition designed to encourage development of new technologies...

  18. Asia's new challenges

    DEFF Research Database (Denmark)

    Brach, Juliana; Vang, Jan

    2012-01-01

    Asian countries are currently undergoing significant changes with respect to their role in and interaction with the international economy. Despite their heterogeneity, Asian countries share the common aim to upgrade capacities, skills and capabilities. This paper aims at unpacking the challenges...

  19. The challenge of implementation

    DEFF Research Database (Denmark)

    Andersen, Karen Heide Hauge

    2015-01-01

    concepts in daily teaching, as it is strongly encouraged by policy makers and educations. This paper aims to discuss how lecturers experience the challenge of teaching their own discipline while being imposed to embrace and promote innovation and entrepreneurship teaching. Through a single study case of...

  20. Tackling the Unemployment Challenge

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    As the world's largest economy in transition, Chinafaces a severe unemployment challenge. With aworking population of 751 million, China'sunemployment rate stands at more than l O% in urbanareas," including rural surplus laborers, it is astaggering 20%. Since assuming office in March

  1. The blind hens’ challenge

    DEFF Research Database (Denmark)

    Sandøe, Peter; Hocking, Paul M.; Forkman, Björn;

    2014-01-01

    repellent, yet 'welfare-only' positions appear to be committed to endorsing this possibility if it produces welfare gains. We call this the 'Blind Hens' Challenge'. In this paper, we argue that there are both empirical and theoretical reasons why even those adopting 'welfare-only' views should be concerned...

  2. MALL: The Pedagogical Challenges

    Science.gov (United States)

    Burston, Jack

    2014-01-01

    In this paper the development of mobile-assisted language learning (MALL) over the past 20 years is reviewed with a particular focus on the pedagogical challenges facing its exploitation. Following a consideration of the definition of mobile learning, the paper describes the dominant mobile technologies upon which MALL applications have been…

  3. Overcoming Breastfeeding Challenges

    Medline Plus

    Full Text Available ... and Human Services Office on Women's Health Skip Navigation Skip top navigation Home A-Z Health Topics ePublications News About Us Contact Us Text size | Print | Skip left navigation It's Only Natural Planning ahead Overcoming challenges Overcoming ...

  4. Electric Vehicle Battery Challenge

    Science.gov (United States)

    Roman, Harry T.

    2014-01-01

    A serious drawback to electric vehicles [batteries only] is the idle time needed to recharge their batteries. In this challenge, students can develop ideas and concepts for battery change-out at automotive service stations. Such a capability would extend the range of electric vehicles.

  5. A Challenge to Watson

    Science.gov (United States)

    Detterman, Douglas K.

    2011-01-01

    Watson's Jeopardy victory raises the question of the similarity of artificial intelligence and human intelligence. Those of us who study human intelligence issue a challenge to the artificial intelligence community. We will construct a unique battery of tests for any computer that would provide an actual IQ score for the computer. This is the same…

  6. The Moon Challenge

    Science.gov (United States)

    Fitzsimmons, Pat; Leddy, Diana; Johnson, Lindy; Biggam, Sue; Locke, Suzan

    2013-01-01

    This article describes a first-grade research project that incorporates trade books and challenges misconceptions. Educators see the power of their students' wonder at work in their classrooms on a daily basis. This wonder must be nourished by students' own experiences--observing the moon on a crystal clear night--as well as by having…

  7. Ecommerce: Ongoing Challenges

    Directory of Open Access Journals (Sweden)

    Derek Mohammed

    2010-08-01

    Full Text Available This paper examines some of the challenges of online marketing, including the importance of adding online marketing to corporation budgets. A review of the pros and cons of social networking on the Internet, when used as a marketing tool by companies is presented. In addition, new forms of Internet shoppers and new niches for companies are identified

  8. Challenging the Boundaries

    DEFF Research Database (Denmark)

    Nørgaard, Nina

    2004-01-01

    To many people, challenging the boundaries between the traditional disciplines in foreign language studies means doing cultural studies. The aim of this article is to pull in a different direction by suggesting how the interface between linguistics and literature may be another fertile field to e...

  9. Challenging and valuable

    OpenAIRE

    Van Hal, J.D.M.

    2008-01-01

    Challenging and valuable Inaugural speech given on May 7th 2008 at the occasion of the acceptance of the position of Professor Sustainable Housing Transformation at the faculty of Architeeture of the Delft University of Technology by Prof. J.D.M. van Hal MSc PhD.

  10. Hopes and Challenges

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China tops the medal tally again at the Asian Games but still faces challenges in some events The curtain of the 16th Asian Games has fallen, but the 15 days of exciting competitions will be recorded in the history of the Games.

  11. Ecommerce: Ongoing Challenges

    OpenAIRE

    Derek Mohammed

    2010-01-01

    This paper examines some of the challenges of online marketing, including the importance of adding online marketing to corporation budgets. A review of the pros and cons of social networking on the Internet, when used as a marketing tool by companies is presented. In addition, new forms of Internet shoppers and new niches for companies are identified

  12. The diesel challenge

    International Nuclear Information System (INIS)

    This article is focused on the challenges being faced by the diesel producer and these include a number of interesting developments which illustrate the highly competitive world of the European refiner. These include: The tightening quality requirements being legislated coupled with the availability of the ''city diesel'' from Scandinavia and elsewhere which is already being sold into the market. For a time there will be a clear means of product differentiation. One of the key questions is whether the consumer will value the quality difference; a growing demand for diesel which is outstripping the growth in gasoline demand and causing refiners headaches when it comes to balancing their supply/demand barrels; the emergence of alternative fuels which are challenging the traditional markets of the refiner and in particular, the niche markets for the higher quality diesel fuels. All of this at a time of poor margins and over-capacity in the industry with further major challenges ahead such as fuel oil disposal, tighter environmental standards and the likelihood of heavier, higher sulphur crude oils in the future. Clearly, in such a difficult and highly-competitive business environment it will be important to find low-cost solutions to the challenges of the diesel quality changes. An innovative approach will be required to identify the cheapest and best route to enable the manufacture of the new quality diesel. (Author)

  13. Fortification Challenges and Needs

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Experience in many parts of the developing world has shown thatfood fortification offers a cost-effective and sustainable solution to the problem of micronutrient malnutrition. Building on the advances in science and technology and backed by studies on the economic benefits of fortification programs, governments and industry are beginning to respond positively to the call of nutrition advocates to adopt fortification as a long-term strategy. On the other hand, formidable challenges still remain in many countries in Asia, constraining the widespread adoption of this strategy. The science and technology community needs to provide adequate scientific and technological information as basis for planning and decision making. The government faces the challenge of providing the enabling environment for all stakeholders to cooperate in the fortification effort. Industry faces the challenge of adapting its production system to the requirements of fortification in order that they can contribute to social objectives while pursuing their economic objectives. The international and bilateral aid agencies need to seek tried and innovative ways to support the multiple players of food fortification, as these players in turn face the challenges that confront them.

  14. Fortification Challenges and Needs

    Institute of Scientific and Technical Information of China (English)

    RODOLFOF.FLORENTINO

    2001-01-01

    Experience in many parts of the developing world has shown that food fortification offers a costeffective and sustainable solution to the problem of micronutrient malnutrition.Building on the advances in science and technology and backed by studies on the economic benefits of fortification programs,govenments and industry are beginning to respond positively to the call of nutrition advocates to adopt fortification as a long-term strategy.On the other hand,formidable challenges still remain in many countries in Asia,constraining the widespread adoption of this strategy,The science and technology community needs to provide adequate scientific and technological information as basis for planning and decision making,The governent faces the challenge of providing the enabling environment for all stakeholders to cooperate in the fortification effort.Industry faces the challenge of adapting its production system to the requirements of fortification in oreder that they can contribute to social bojectives while pursuing their economic objectives,The international and bilateral aid agencies need to seek tried and innovative ways to support the multiple players of food fortification,as these players in turn face the challenges that confront them.

  15. The Clay Challenge Continues...

    Science.gov (United States)

    Coy, Mary

    2007-01-01

    It was time for yet another challenge. Bright colored glazes were on hiatus; earth tones and mixed media took center stage. Inspiration was provided this time by the myriad Native American potters from the desert Southwest. The project: create a coil pot that demonstrates interesting form and good artistry and reflects, through symbolism or mixed…

  16. Roll bonding of strained aluminium

    DEFF Research Database (Denmark)

    Staun, Jakob M.

    2003-01-01

    This report investigates roll bonding of pre-strained (å ~ 4) aluminium sheets to produce high strain material from high purity aluminium (99.996%) and commercial pure aluminium (99.6%). The degree of bonding is investigated by optical microscopy and ultrasonic scanning. Under the right...... circumstances both materials show good bonding, but the high purity material is excluded because of recrystallisation and the resulting loss of mechanical properties. The effect of cross stacking and roll bonding pre-strained sheets of the commercial purity material is investigated and some dependence of the...... cross rolled volume fraction is found. To further asses this effect, and the anisotropy, it is necessary to acquire knowledge about both texture and microstructure, e.g. by TEM. Roll bonding of pre-strained aluminium is found to be a possible alternative to ARB in the quest for ultra-fine grained...

  17. Price level targeting

    OpenAIRE

    Shukayev, Malik; Ueberfeldt, Alexander

    2010-01-01

    Various papers have suggested that Price-Level targeting is a welfare improving policy relative to Inflation targeting. From a practical standpoint, this raises an important yet unanswered question: What is the optimal price index to target? This paper derives the optimal price level targeting index defined over the eight main components of the Consumer Price Index. It finds that such an index places a heavier weight, relative to the expenditure weight, on sectors with slow price adjustments....

  18. Multilayer polymer microspot targets

    International Nuclear Information System (INIS)

    Last year the authors reported on the development of a seeded microspot x-ray diagnostic target. This target consisted of a 300-μm-diam, 2-μm-thick disk of silicon or sulfur-seeded hydrocarbon polymer nested tightly in a hole in a 2-μm-thick film of pure hydrocarbon polymer. This year they extended our work on the microspot target, fully encapsulating the microspot in what they call the multilayer polymer microspot target

  19. Target Price Accuracy

    OpenAIRE

    Alexander G. Kerl

    2011-01-01

    This study analyzes the accuracy of forecasted target prices within analysts’ reports. We compute a measure for target price forecast accuracy that evaluates the ability of analysts to exactly forecast the ex-ante (unknown) 12-month stock price. Furthermore, we determine factors that explain this accuracy. Target price accuracy is negatively related to analyst-specific optimism and stock-specific risk (measured by volatility and price-to-book ratio). However, target price accuracy is positive...

  20. The Targeting of Advertising

    OpenAIRE

    Ganesh Iyer; David Soberman; J. Miguel Villas-Boas

    2005-01-01

    An important question that firms face in advertising is developing effective media strategy. Major improvements in the quality of consumer information and the growth of targeted media vehicles allow firms to precisely target advertising to consumer segments within a market. This paper examines advertising strategy when competing firms can target advertising to different groups of consumers within a market. With targeted advertising, we find that firms advertise more to consumers who have a st...

  1. TARGET COSTING FUNCTIONS

    OpenAIRE

    Dimi OFILEANU

    2015-01-01

    This article aims to highlight the concept of Target Costing. Based on the characteristics of Target Costing, identified in specialized literature, the article presents its main advantages and disadvantages. Also, a comparison is being made between Target Cost and Traditional Cost (in its traditional form, the cost represents an independent variable on the basis of which the sell price is established; and in the Target Cost form the cost represents a dependent variable which is determined on ...

  2. Attenuation of a virulent Aeromonas hydrophila with novobiocin and pathogenic characterization of the novobiocin-resistant strain

    Science.gov (United States)

    A novobiocin-resistant strain AH11NOVO was obtained from a virulent A. hydrophila strain AH11P through selection of resistance to novobiocin. AH11NOVO was found to be avirulent to channel catfish whereas AH11P was virulent. When AH11NOVO vaccinated channel catfish were challenged with AH11P at 14 da...

  3. Attenuation of a virulent Aeromonas hydrophila with novobiocin and pathogenic characterization of the novobiocin-resistant strain

    Science.gov (United States)

    A novobiocin-resistant strain AH11NOVO was obtained from a virulent A. hydrophila strain AH11P through selection of resistance to novobiocin. AH11NOVO was found to be avirulent to channel catfish (Ictalurus punctatus) whereas AH11P was virulent. When AH11NOVO vaccinated channel catfish were challeng...

  4. Covalent functionalization of strained graphene

    OpenAIRE

    Boukhvalov, Danil W.; Son, Young-Woo

    2012-01-01

    Enhancement of the chemical activity of graphene is evidenced by first-principles modelling of chemisorption of the hydrogen, fluorine, oxygen and hydroxyl groups on strained graphene. For the case of negative strain or compression, chemisorption of the single hydrogen, fluorine or hydroxyl group is energetically more favourable than those of their pairs on different sublattices. This behaviour stabilizes the magnetism caused by the chemisorption being against its destruction by the pair form...

  5. Hypervirulent strains of Clostridium difficile

    OpenAIRE

    Cookson, Barry

    2007-01-01

    North America has seen increasing numbers of hospitalised patients and others in nursing homes and the community, with more severe Clostridium difficile associated diarrhoea. This is also described in Northern Europe and surveillance systems are being developed or improved to monitor the situation. One strain (ribotype O27) is described in detail and, like other emerging strains, is demonstrating increasing antimicrobial resistance, notably to quinolone antibiotics. However, its association w...

  6. Biocontrol mechanisms of Thrichoderma strains

    OpenAIRE

    Benítez Fernández, Concepción Tahía; Rincón Romero, Ana María; Limón Mirón, María del Carmen; Carballo Codón, Antonio

    2004-01-01

    The genus Trichoderma comprises a great number of fungal strains that act as biological control agents, the antagonistic properties of which are based on the activation of multiple mechanisms. Trichoderma strains exert biocontrol against fungal phytopathogens either indirectly, by competing for nutrients and space, modifying the environmental conditions, or promoting plant growth and plant defensive mechanisms and antibiosis, or directly, by mechanisms such as mycoparasitism. These indirect a...

  7. Influenza M2 virus-like particles confer a broader range of cross protection to the strain-specific pre-existing immunity.

    Science.gov (United States)

    Kim, Min-Chul; Lee, Yu-Na; Hwang, Hye Suk; Lee, Young-Tae; Ko, Eun-Ju; Jung, Yu-Jin; Cho, Min Kyoung; Kim, Yu-Jin; Lee, Jong Seok; Ha, Suk-Hoon; Kang, Sang-Moo

    2014-10-01

    Immunity in humans with annual vaccination does not provide effective protection against antigenically distinct strains. As an approach to improve cross-protection in the presence of pre-existing strain-specific immunity, we investigated the efficacy of heterologous and heterosubtypic protection in previously vaccinated mice at earlier times after subsequent immunization with conserved-antigenic target influenza M2 ectodomain (M2e) virus-like particle vaccine (M2e5× VLP). Immunization of mice with H1N1 split vaccine induced virus specific antibodies to homologous influenza virus but did not provide heterosubtypic hemagglutination inhibiting antibody responses and cross-protection. However, subsequent M2e5× VLP immunization induced an M2e specific antibody response as well as interferon-γ (IFN-γ) producing cells in systemic and mucosal sites. Upon lethal challenge with H3N2 or H5N1 subtype influenza viruses, subsequently immunized mice with M2e5× VLP were well protected against heterosubtypic influenza viruses. These results provide evidence that non-seasonal immunization with M2e5× VLP, an experimental candidate for universal vaccine, is a promising approach for broadening the cross-protection even in the presence of strain-specific immunity. PMID:25171841

  8. Development of a biomarker for Geobacter activity and strain composition: Proteogenomic analysis of the citrate synthase protein during bioremediation of U(VI)

    Energy Technology Data Exchange (ETDEWEB)

    Wilkins, M.J.; Callister, S.J.; Miletto, M.; Williams, K.H.; Nicora, C.D.; Lovley, D.R.; Long, P.E.; Lipton, M.S.

    2010-02-15

    Monitoring the activity of target microorganisms during stimulated bioremediation is a key problem for the development of effective remediation strategies. At the US Department of Energy's Integrated Field Research Challenge (IFRC) site in Rifle, CO, the stimulation of Geobacter growth and activity via subsurface acetate addition leads to precipitation of U(VI) from groundwater as U(IV). Citrate synthase (gltA) is a key enzyme in Geobacter central metabolism that controls flux into the TCA cycle. Here, we utilize shotgun proteomic methods to demonstrate that the measurement of gltA peptides can be used to track Geobacter activity and strain evolution during in situ biostimulation. Abundances of conserved gltA peptides tracked Fe(III) reduction and changes in U(VI) concentrations during biostimulation, whereas changing patterns of unique peptide abundances between samples suggested sample-specific strain shifts within the Geobacter population. Abundances of unique peptides indicated potential differences at the strain level between Fe(III)-reducing populations stimulated during in situ biostimulation experiments conducted a year apart at the Rifle IFRC. These results offer a novel technique for the rapid screening of large numbers of proteomic samples for Geobacter species and will aid monitoring of subsurface bioremediation efforts that rely on metal reduction for desired outcomes.

  9. Seven challenges for neuroscience.

    Science.gov (United States)

    Markram, Henry

    2013-01-01

    Although twenty-first century neuroscience is a major scientific enterprise, advances in basic research have not yet translated into benefits for society. In this paper, I outline seven fundamental challenges that need to be overcome. First, neuroscience has to become "big science" - we need big teams with the resources and competences to tackle the big problems. Second, we need to create interlinked sets of data providing a complete picture of single areas of the brain at their different levels of organization with "rungs" linking the descriptions for humans and other species. Such "data ladders" will help us to meet the third challenge - the development of efficient predictive tools, enabling us to drastically increase the information we can extract from expensive experiments. The fourth challenge goes one step further: we have to develop novel hardware and software sufficiently powerful to simulate the brain. In the future, supercomputer-based brain simulation will enable us to make in silico manipulations and recordings, which are currently completely impossible in the lab. The fifth and sixth challenges are translational. On the one hand we need to develop new ways of classifying and simulating brain disease, leading to better diagnosis and more effective drug discovery. On the other, we have to exploit our knowledge to build new brain-inspired technologies, with potentially huge benefits for industry and for society. This leads to the seventh challenge. Neuroscience can indeed deliver huge benefits but we have to be aware of widespread social concern about our work. We need to recognize the fears that exist, lay them to rest, and actively build public support for neuroscience research. We have to set goals for ourselves that the public can recognize and share. And then we have to deliver on our promises. Only in this way, will we receive the support and funding we need. PMID:24139651

  10. An actionable climate target

    Science.gov (United States)

    Geden, Oliver

    2016-05-01

    The Paris Agreement introduced three mitigation targets. In the future, the main focus should not be on temperature targets such as 2 or 1.5 °C, but on the target with the greatest potential to effectively guide policy: net zero emissions.

  11. Deletion of the Pichia pastoris KU70 homologue facilitates platform strain generation for gene expression and synthetic biology.

    Directory of Open Access Journals (Sweden)

    Laura Näätsaari

    Full Text Available Targeted gene replacement to generate knock-outs and knock-ins is a commonly used method to study the function of unknown genes. In the methylotrophic yeast Pichia pastoris, the importance of specific gene targeting has increased since the genome sequencing projects of the most commonly used strains have been accomplished, but rapid progress in the field has been impeded by inefficient mechanisms for accurate integration. To improve gene targeting efficiency in P. pastoris, we identified and deleted the P. pastoris KU70 homologue. We observed a substantial increase in the targeting efficiency using the two commonly known and used integration loci HIS4 and ADE1, reaching over 90% targeting efficiencies with only 250-bp flanking homologous DNA. Although the ku70 deletion strain was noted to be more sensitive to UV rays than the corresponding wild-type strain, no lethality, severe growth retardation or loss of gene copy numbers could be detected during repetitive rounds of cultivation and induction of heterologous protein production. Furthermore, we demonstrated the use of the ku70 deletion strain for fast and simple screening of genes in the search of new auxotrophic markers by targeting dihydroxyacetone synthase and glycerol kinase genes. Precise knock-out strains for the well-known P. pastoris AOX1, ARG4 and HIS4 genes and a whole series of expression vectors were generated based on the wild-type platform strain, providing a broad spectrum of precise tools for both intracellular and secreted production of heterologous proteins utilizing various selection markers and integration strategies for targeted or random integration of single and multiple genes. The simplicity of targeted integration in the ku70 deletion strain will further support protein production strain generation and synthetic biology using P. pastoris strains as platform hosts.

  12. Deletion of the Pichia pastoris KU70 homologue facilitates platform strain generation for gene expression and synthetic biology.

    Science.gov (United States)

    Näätsaari, Laura; Mistlberger, Beate; Ruth, Claudia; Hajek, Tanja; Hartner, Franz S; Glieder, Anton

    2012-01-01

    Targeted gene replacement to generate knock-outs and knock-ins is a commonly used method to study the function of unknown genes. In the methylotrophic yeast Pichia pastoris, the importance of specific gene targeting has increased since the genome sequencing projects of the most commonly used strains have been accomplished, but rapid progress in the field has been impeded by inefficient mechanisms for accurate integration. To improve gene targeting efficiency in P. pastoris, we identified and deleted the P. pastoris KU70 homologue. We observed a substantial increase in the targeting efficiency using the two commonly known and used integration loci HIS4 and ADE1, reaching over 90% targeting efficiencies with only 250-bp flanking homologous DNA. Although the ku70 deletion strain was noted to be more sensitive to UV rays than the corresponding wild-type strain, no lethality, severe growth retardation or loss of gene copy numbers could be detected during repetitive rounds of cultivation and induction of heterologous protein production. Furthermore, we demonstrated the use of the ku70 deletion strain for fast and simple screening of genes in the search of new auxotrophic markers by targeting dihydroxyacetone synthase and glycerol kinase genes. Precise knock-out strains for the well-known P. pastoris AOX1, ARG4 and HIS4 genes and a whole series of expression vectors were generated based on the wild-type platform strain, providing a broad spectrum of precise tools for both intracellular and secreted production of heterologous proteins utilizing various selection markers and integration strategies for targeted or random integration of single and multiple genes. The simplicity of targeted integration in the ku70 deletion strain will further support protein production strain generation and synthetic biology using P. pastoris strains as platform hosts. PMID:22768112

  13. Strain evaluation in fatigue analysis

    International Nuclear Information System (INIS)

    Thermoplastic analysis and more precisely fatigue analysis of nuclear components working at high temperature is usually very difficult and very expensive. Simplified methods have been proposed and are generally used to perform analysis of these structures. These simplified methods require elastic analysis of the component. For a fatigue analysis it is necessary to obtain a very precise value of the strains so the elastic strains must be corrected in order to take plasticity into account. This later appears in two different ways. Non linearity of material which induces strain amplification when working in the plastic field especially near by geometric discontinuities. That can be taken into account with a coefficient Ke. Triaxiality and isovolumic character of strains in the plastic field. That also induces strain amplification with regard to elastic computation. It is proposed in this work to introduce a coefficient Kv to estimate this strain amplification. Several elastic and plastic calculations for typical geometries, have been done in order to test the importance of these parameters and to set up methods for evaluating the coefficients Ke and Kv

  14. What "helps" tumors evade vascular targeting treatment?

    Institute of Scientific and Technical Information of China (English)

    SI Zhi-chao; LIU Jie

    2008-01-01

    Objective To throw a light on the possible factors which might induce resistance of vascular targeting treatment in tumors by reviewing the recent publications in the field of tumor angiogenesis and vascular targeting treatment.Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1971 to January 2008. The search terms were "angiogenesis", "vascular targeting treatment" and "endothelial progenitor cells".Study selection Articles involved in the possible influence factors during angiogenesis and vascular targeting treatment were selected, including angiogenic or anti-angiogenic mechanism, tumor vasculature, tumor cells, cancer stem cells and endothelial progenitor cells.Results As a promising strategy vascular targeting treatment still has experimental and clinical setbacks which may term tumor vasculature's resistance to anti-angiogenesis agents. There are several possible explanations for such a resistance that might account for clinical and preclinical failures of anti-angiogenic treatment against tumor.Proangiogenic effect of hypoxia, normal tumor vasculature, escape of tumor cells and tumor vasculogenesis are included.This review reveals some clues which might be helpful to direct future research in order to remove obstacles to vascular targeting treatment.Conclusions Generally and undoubtedly vascular targeting treatment remains a promising strategy. But we still have to realize the existence of a challenging future. Further research is required to enhance our knowledge of vascular targeting treatment strategy before it could make a more substantial success.

  15. Fabrication and Characterization of Fast Ignition Targets

    International Nuclear Information System (INIS)

    Fast ignition is a novel scheme for achieving laser fusion. A class of these targets involves cone mounted CH shells. We have been fabricating such targets with shells with a wide variety of diameters and wall thicknesses for several years at General Atomics. In addition, recently such shells were needed for implosion experiments at Laboratory for Laser Energetics (LLE) that for the first time were required to be gas retentive. Fabrication of these targets requires producing appropriate cones and shells, assembling the targets, and characterization of the assembled targets. The cones are produced using micromachining and plating techniques. The shells are fabricated using the depolymerizable mandrel technique followed by micromachining a hole for the cone. The cone and the shell then need to be assembled properly for gas retention and precisely in order to position the cone tip at the desired position within the shell. Both are critical for the fast ignition experiments. The presence of the cone in the shell creates new challenges in characterization of the assembled targets. Finally, for targets requiring a gas fill, the cone-shell assembly needs to be tested for gas retention and proper strength at the glue joint. This paper presents an overview of the developmental efforts and technical issues addressed during the fabrication of fast ignition targets

  16. FABRICATION AND CHARACTERIZATION OF FAST IGNITION TARGETS

    International Nuclear Information System (INIS)

    OAK-B135 Fast ignition is a novel scheme for achieving laser fusion. A class of these targets involves cone mounted CH shells. The authors have been fabricating such targets with shells with a wide variety of diameters and wall thicknesses for several years at General Atomics. In addition, recently such shells were needed for implosion experiments at Laboratory for Laser Energetics (LLE) that for the first time were required to be gas retentive. Fabrication of these targets requires producing appropriate cones and shells, assembling the targets, and characterization of the assembled targets. The cones are produced using micromachining and plating techniques. The shells are fabricated using the depolymerizable mandrel technique followed by micromachining a hole for the cone. The cone and the shell then need to be assembled properly for gas retention and precisely in order to position the cone tip at the desired position within the shell. Both are critical for the fast ignition experiments. The presence of the cone in the shell creates new challenges in characterization of the assembled targets. Finally, for targets requiring a gas fill, the cone-shell assembly needs to be tested for gas retention and proper strength at the glue joint. This paper presents an overview of the developmental efforts and technical issues addressed during the fabrication of fast ignition targets

  17. Physiological strain and countermeasures with firefighting.

    Science.gov (United States)

    Cheung, S S; Petersen, S R; McLellan, T M

    2010-10-01

    Protective clothing is integral to the task of firefighting, but at the same time can increase physiological strain and impair work capacity. Encapsulation of the head and the high thermal resistance and/or low water vapor permeability of the clothing ensemble impede evaporative heat dissipation, thus elevating the rate of heat storage and creating a state of uncompensable heat stress (UHS). In addition, the additional weight from carrying a supplemental air supply and the greater respiratory work of breathing through a regulator can create a negative spiral of thermal hyperpnea from greater respiratory demands and metabolic heat production. The elevated respiratory demands also increase cardiac strain and potentially the risk for myocardial events. Tolerance time during UHS is determined by three factors: the core temperature at the beginning of the heat stress exposure, the core temperature that can be tolerated before exhaustion or collapse ensues, and the rate of increase in core temperature from the beginning to end of the heat stress exposure. Protective clothing is often employed in highly dynamic environments, making portability, longevity and integration with the task requirements and clothing critical design characteristics for countermeasures. To date, most countermeasures have been relatively indirect in nature, primarily with alterations in work scheduling along with physiological manipulations such as cooling manipulations during recovery periods. Advances are required in materials science to develop lighter and less restrictive protective equipment, concurrent with cooling strategies that target specific regions or which can be effectively implemented during exercise. PMID:21029197

  18. European molecular epidemiology and strain diversity of feline calicivirus.

    Science.gov (United States)

    Hou, J; Sánchez-Vizcaíno, F; McGahie, D; Lesbros, C; Almeras, T; Howarth, D; O'Hara, V; Dawson, S; Radford, A D

    2016-01-30

    Feline calicivirus (FCV) causes a variable syndrome of upper respiratory tract disease, mouth ulcers and lameness. A convenience-based prospective sample of oropharyngeal swabs (n=426) was obtained from five countries (France, Germany, Greece, Portugal and the UK). The prevalence of FCV by virus isolation was 22.2 per cent. Multivariable analysis found that animals presenting with lymphoplasmacytic gingivitis stomatitis complex were more likely to test positive for FCV infection. Furthermore, vaccinated cats up to 48 months of age were significantly less likely to be infected with FCV than unvaccinated animals of similar ages. Phylogenetic analysis based on consensus sequences for the immunodominant region of the capsid gene from 72 FCV isolates identified 46 strains. Thirteen of the 14 strains with more than one sequence were restricted to individual regions or sites in individual countries; the exception was a strain present in two sites close to each other in France. Four strains were present in more than one household. Five colonies, four of which were rescue shelters, had multiple strains within them. Polymerase sequence suggested possible rare recombination events. These locally, nationally and internationally diverse FCV populations maintain a continuous challenge to the control of FCV infection and disease. PMID:26811440

  19. Managing neurocysticercosis: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Fogang YF

    2015-10-01

    Full Text Available Yannick Fogoum Fogang, Abdoul Aziz Savadogo, Massaman Camara, Dènahin Hinnoutondji Toffa, Anna Basse, Adjaratou Djeynabou Sow, Mouhamadou Mansour Ndiaye Neurology Department, Fann Teaching Hospital, Cheikh Anta Diop University, Dakar, Senegal Abstract: Taenia solium neurocysticercosis (NCC is a major cause of neurological morbidity in the world. Variability in the neuropathology and clinical presentation of NCC often make it difficult to diagnose and manage. Diagnosis of NCC can be challenging especially in endemic and resource-limited countries where laboratory and imaging techniques are often lacking. NCC management can also be challenging as current treatment options are limited and involve symptomatic agents, antiparasitic agents, or surgery. Although antiparasitic treatment probably reduces the number of active lesions and long-term seizure frequency, its efficacy is limited and strategies to improve treatment regimens are warranted. Treatment decisions should be individualized in relation to the type of NCC. Initial measures should focus on symptomatic management, with antiparasitic therapy only to be considered later on, when appropriate. Symptomatic treatment remains the cornerstone in NCC management which should not only focuses on epilepsy, but also on other manifestations that cause considerable burden (recurrent headaches, cognitive decline. Accurate patients' categorization, better antiparasitic regimens, and definition of new clinical outcomes for trials on NCC could improve management quality and prognosis of NCC. Prevention strategies targeting tapeworm carriers and infected pigs are yielding good results in local models. If local elimination of transmission is confirmed and replicated, this will open the door to cysticercosis eradication efforts worldwide. Keywords: neurocysticercosis, Taenia solium, epilepsy, headache, albendazole, praziquantel

  20. Systemic resistance and lipoxygenase-related defence response induced in tomato by Pseudomonas putida strain BTP1

    Directory of Open Access Journals (Sweden)

    Dommes Jacques

    2008-11-01

    Full Text Available Abstract Background Previous studies showed the ability of Pseudomonas putida strain BTP1 to promote induced systemic resistance (ISR in different host plants. Since ISR is long-lasting and not conducive for development of resistance of the targeted pathogen, this phenomenon can take part of disease control strategies. However, in spite of the numerous examples of ISR induced by PGPR in plants, only a few biochemical studies have associated the protective effect with specific host metabolic changes. Results In this study, we showed the protective effect of this bacterium in tomato against Botrytis cinerea. Following treatment by P. putida BTP1, analyses of acid-hydrolyzed leaf extracts showed an accumulation of antifungal material after pathogen infection. The fungitoxic compounds thus mainly accumulate as conjugates from which active aglycones may be liberated through the activity of hydrolytic enzymes. These results suggest that strain BTP1 can elicit systemic phytoalexin accumulation in tomato as one defence mechanism. On another hand, we have shown that key enzymes of the lipoxygenase pathway are stimulated in plants treated with the bacteria as compared with control plants. Interestingly, this stimulation is observed only after pathogen challenge in agreement with the priming concept almost invariably associated with the ISR phenomenon. Conclusion Through the demonstration of phytoalexin accumulation and LOX pathway stimulation in tomato, this work provides new insights into the diversity of defence mechanisms that are inducible by non-pathogenic bacteria in the context of ISR.

  1. Small Space Launch: Origins & Challenges

    Science.gov (United States)

    Freeman, T.; Delarosa, J.

    2010-09-01

    The United States Space Situational Awareness capability continues to be a key element in obtaining and maintaining the high ground in space. Space Situational Awareness satellites are critical enablers for integrated air, ground and sea operations, and play an essential role in fighting and winning conflicts. The United States leads the world space community in spacecraft payload systems from the component level into spacecraft, and in the development of constellations of spacecraft. In the area of launch systems that support Space Situational Awareness, despite the recent development of small launch vehicles, the United States launch capability is dominated by an old, unresponsive and relatively expensive set of launchers in the Expandable, Expendable Launch Vehicles (EELV) platforms; Delta IV and Atlas V. The United States directed Air Force Space Command to develop the capability for operationally responsive access to space and use of space to support national security, including the ability to provide critical space capabilities in the event of a failure of launch or on-orbit capabilities. On 1 Aug 06, Air Force Space Command activated the Space Development & Test Wing (SDTW) to perform development, test and evaluation of Air Force space systems and to execute advanced space deployment and demonstration projects to exploit new concepts and technologies, and rapidly migrate capabilities to the warfighter. The SDTW charged the Launch Test Squadron (LTS) with the mission to develop the capability of small space launch, supporting government research and development space launches and missile defense target missions, with operationally responsive spacelift for Low-Earth-Orbit Space Situational Awareness assets as a future mission. This new mission created new challenges for LTS. The LTS mission tenets of developing space launches and missile defense target vehicles were an evolution from the squadrons previous mission of providing sounding rockets under the Rocket

  2. A new piperidinol derivative targeting mycolic acid transport in Mycobacterium abscessus.

    Science.gov (United States)

    Dupont, Christian; Viljoen, Albertus; Dubar, Faustine; Blaise, Mickaël; Bernut, Audrey; Pawlik, Alexandre; Bouchier, Christiane; Brosch, Roland; Guérardel, Yann; Lelièvre, Joël; Ballell, Lluis; Herrmann, Jean-Louis; Biot, Christophe; Kremer, Laurent

    2016-08-01

    The natural resistance of Mycobacterium abscessus to most commonly available antibiotics seriously limits chemotherapeutic treatment options, which is particularly challenging for cystic fibrosis patients infected with this rapid-growing mycobacterium. New drugs with novel molecular targets are urgently needed against this emerging pathogen. However, the discovery of such new chemotypes has not been appropriately performed. Here, we demonstrate the utility of a phenotypic screen for bactericidal compounds against M. abscessus using a library of compounds previously validated for activity against M. tuberculosis. We identified a new piperidinol-based molecule, PIPD1, exhibiting potent activity against clinical M. abscessus strains in vitro and in infected macrophages. Treatment of infected zebrafish with PIPD1 correlated with increased embryo survival and decreased bacterial burden. Whole genome analysis of M. abscessus strains resistant to PIPD1 identified several mutations in MAB_4508, encoding a protein homologous to MmpL3. Biochemical analyses demonstrated that while de novo mycolic acid synthesis was unaffected, PIPD1 strongly inhibited the transport of trehalose monomycolate, thereby abrogating mycolylation of arabinogalactan. Mapping the mutations conferring resistance to PIPD1 on a MAB_4508 tridimensional homology model defined a potential PIPD1-binding pocket. Our data emphasize a yet unexploited chemical structure class against M. abscessus infections with promising translational development possibilities. PMID:27121350

  3. Strains, Mechanism, and Perspective: Salmonella-Based Cancer Therapy

    Science.gov (United States)

    Wang, Cheng-Zhi; Kazmierczak, Robert A.; Eisenstark, Abraham

    2016-01-01

    Recently, investigation of bacterial-based tumor therapy has regained focus due to progress in molecular, cellular, and microbial biology. Many bacteria such as Salmonella, Listeria, Escherichia, and Clostridium have proved to have tumor targeting and in some cases even tumor-destroying phenotypes. Furthermore, bacterial clinical treatments for cancer have been improved by combination with other therapeutic methods such as chemotherapeutic drugs and radioactive agents. Synthetic biology techniques have also driven the development of new bacterial-based cancer therapies. However, basic questions about the mechanisms of bacterial-mediated tumor targeting and destruction are still being elucidated. In this review, we focus on three tumor-therapeutic Salmonella models, the most intensively studied bacterial genus in this field. One of these Salmonella models is our Salmonella enterica serovar Typhimurium LT2 derived strain CRC2631, engineered to minimize toxicity but maximize tumor-targeting and destruction effects. The other two are VNP20009 and A1-R. We compare the means by which these therapeutic candidate strain models were selected for study, their tumor targeting and tumor destruction phenotypes in vitro and in vivo, and what is currently known about the mechanisms by which they target and destroy tumors.

  4. Isolation and initial characterization of thermoresistant RIF tumor cell strains

    International Nuclear Information System (INIS)

    Heat-resistant cell strains were obtained from RIF-1 mouse tumor cells by repeated heatings of cells derived from survivors of previous heating cycles (60 min; 450C). Twenty thermally resistant (TR) strains were derived from single cells that had survived 11 heating and regrowth cycles. These were then analyzed for appropriate characteristics in vitro and in vivo. In vitro we looked for: marked heat resistance; high plating efficiency; growth rate similar to that of RIF-1 cells; and no obvious morphological abnormalities. In syngeneic hosts, we looked for: ability of the cells to form tumors whose growth rates were similar to that of RIF-1 tumors; high cellular heat resistance; good plating efficiency of tumor-derived cells; and low immunogenicity. Five strains having these desired characteristics were analyzed for survival kinetics. The heat-resistant phenotype was found to be stable in vitro, although partial reversion in vivo was seen occasionally. The break in the Arrhenius plot was found to occur at 450C in TR strains versus 430C in RIF-1. All TR strains and the RIF-1 line developed similar levels of thermotolerance (as defined by slope ratios) when given isosurvival heat exposures. X-ray responses of TR and RIF-1 cells were indistinguishable both with respect to survival and to heat-induced radiosensitization. While the number of live cells required to give tumor takes in 50% of the recipients for TR strains was appreciably higher than that for RIF-1 cells, radiation-killed cells from none of the strains were able to immunize efficiently against subsequent challenges by live cells

  5. Polarized targets and beams

    International Nuclear Information System (INIS)

    First the experimental situation of the single-pion photoproduction and the photodisintegration of the deuteron is briefly discussed. Then a description of the Bonn polarization facilities is given. The point of main effort is put on the polarized target which plays a vital role in the program. A facility for photon induced double polarization experiments at ELSA will be presented in section 4. Properties of a tensor polarized deuteron target are discussed in section 5. The development in the field of polarized targets, especially on new target materials, enables a new generation of polarized target experiments with (polarized) electrons. Some comments on the use of a polarized target in combination with electron beams will be discussed in section 6. Electron deuteron scattering from a tensor polarized deuteron target is considered and compared with other experimental possibilities. (orig./HSI)

  6. Health Care Challenges in Iran

    Directory of Open Access Journals (Sweden)

    M Davari

    2005-10-01

    Full Text Available All health systems across the world have faced new challenges, which is primarily referable to increasing the cost of health care services as well as growing demands for new and expensive health technologies. The aim of this study is to analyse the main challenges facing the Iranian health system. A review of available governmental and relevant publications about Iranian health care system was undertaken to assess the direction of future healthcare policy. Electronic news agencies, newspapers, and parliament’s electronic news also reviewed to realise policy-makers points of view about the health system. Healthcare services in Iran have had a great success in primary healthcare services in last 25 years, which is mainly attributable to National Health Networks policy. Between 1979 and 2003, average life expectancy at birth increased from 57 to 70 and infant mortality rate fell from 104 to 26 per thousand live births. Active vaccination system, very good distribution and coverage, free end point services, family planning, maternal teaching, and primary referral system are of strong advantages of health networks in Iran. However, the healthcare system is now subject to a range of new pressures that must be addressed. Many of these pressures are common to all health services (rising consumer demands and expectations for expensive new technologies, changing disease patterns, and resources shortage, but some are largely specific to Iran. Financial fairness contribution of the population to health system, responsiveness of health system, overusing new technologies, inadequate integration of health services, and inequitable distribution of the resources are of the main challenges of health system in Iran. In addition, considering demographic changes of the Iranian population in recent decades, which made Iranian population young, potential pressures due to an aging population will reveal in coming years. Many of these pressures relate to policies and

  7. SSFinder: High Throughput CRISPR-Cas Target Sites Prediction Tool

    OpenAIRE

    Santosh Kumar Upadhyay; Shailesh Sharma

    2014-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) system facilitates targeted genome editing in organisms. Despite high demand of this system, finding a reliable tool for the determination of specific target sites in large genomic data remained challenging. Here, we report SSFinder, a python script to perform high throughput detection of specific target sites in large nucleotide datasets. The SSFinder is a user-friendly tool, compatible wit...

  8. Understanding and Targeting Indonesian Young Adult Internet Users

    OpenAIRE

    Andreas Chang

    2010-01-01

    As the number of global internet users increases, companies online advertisement expenditure also grows rapidly. Companies face challenges in targeting the right customers. Understanding which websites are often visited by target users and what they do on the internet will help companies direct their online advertisement to the right target. Using questionnaires, this study examines which sites are most often visited by Indonesian young adult internet users and what they do on the internet. I...

  9. Pseudomonas fluorescens induces strain-dependent and strain-independent host plant responses in defense networks, primary metabolism and photosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Pelletier, Dale A [ORNL; Morrell-Falvey, Jennifer L [ORNL; Karve, Abhijit A [ORNL; Lu, Tse-Yuan S [ORNL; Tschaplinski, Timothy J [ORNL; Tuskan, Gerald A [ORNL; Chen, Jay [ORNL; Martin, Madhavi Z [ORNL; Jawdy, Sara [ORNL; Weston, David [ORNL; Doktycz, Mitchel John [ORNL; Schadt, Christopher Warren [ORNL

    2012-01-01

    Colonization of plants by nonpathogenic Pseudomonas fluorescens strains can confer enhanced defense capacity against a broad spectrum of pathogens. Few studies, however, have linked defense pathway regulation to primary metabolism and physiology. In this study, physiological data, metabolites, and transcript profiles are integrated to elucidate how molecular networks initiated at the root-microbe interface influence shoot metabolism and whole-plant performance. Experiments with Arabidopsis thaliana were performed using the newly identified P. fluorescens GM30 or P. fluorescens Pf-5 strains. Co-expression networks indicated that Pf-5 and GM30 induced a subnetwork specific to roots enriched for genes participating in RNA regulation, protein degradation, and hormonal metabolism. In contrast, only GM30 induced a subnetwork enriched for calcium signaling, sugar and nutrient signaling, and auxin metabolism, suggesting strain dependence in network architecture. In addition, one subnetwork present in shoots was enriched for genes in secondary metabolism, photosynthetic light reactions, and hormone metabolism. Metabolite analysis indicated that this network initiated changes in carbohydrate and amino acid metabolism. Consistent with this, we observed strain-specific responses in tryptophan and phenylalanine abundance. Both strains reduced host plant carbon gain and fitness, yet provided a clear fitness benefit when plants were challenged with the pathogen P. syringae DC3000.

  10. Future Challenges for Vaccinologists.

    Science.gov (United States)

    Thomas, Sunil; Dilbarova, Rima; Rappuoli, Rino

    2016-01-01

    Vaccination is one of the cheapest health-care interventions that have saved more lives than any other drugs or therapies. Due to successful immunization programs we rarely hear about some of the common diseases of the early twentieth century including small pox and polio. Vaccination programs have also helped to increase food production notably poultry, cattle, and milk production due to lower incidence of infectious diseases in farm animals. Though vaccination programs have eradicated several diseases and increased the quality of life there are several diseases that have no effective vaccines. Currently there are no vaccines for cancer, neurodegenerative diseases, autoimmune diseases, as well as infectious diseases like tuberculosis, AIDS, and parasitic diseases including malaria. Abuse of antibiotics has resulted in the generation of several antibiotic-resistant bacterial strains; hence there is a need to develop novel vaccines for antibiotic-resistant microorganisms. Changes in climate is another concern for vaccinologists. Climate change could lead to generation of new strains of infectious microorganisms that would require development of novel vaccines. Use of conventional vaccination strategies to develop vaccines has severe limitations; hence innovative strategies are essential in the development of novel and effective vaccines. PMID:27076124

  11. Challenges in Request Management

    DEFF Research Database (Denmark)

    Sommer, Anita Friis

    2014-01-01

    profitability. This research study seeks to investigate the challenges of RQM in practice. Existing demand chain management literature is used as a basis for developing a RQM framework. RQM is investigated through an explorative research design in a dyadic B2B case study including a global industrial company......Request management (RQM) is a new term used for managing customer requests for new products. It is the counterpart to typical product development processes, which has no direct customer involvement. It is essential to manage customer requests in a structured and efficient way to obtain...... and its customers. The study provides an insight into a new area of supply chain management, including the process activity flow and challenges involved across the process. Furthermore, the method is dyadic including the customer in the case study, which is rare in related research....

  12. Supernova Photometric Classification Challenge

    CERN Document Server

    Kessler, Richard; Jha, Saurabh; Kuhlmann, Stephen

    2010-01-01

    We have publicly released a blinded mix of simulated SNe, with types (Ia, Ib, Ic, II) selected in proportion to their expected rate. The simulation is realized in the griz filters of the Dark Energy Survey (DES) with realistic observing conditions (sky noise, point spread function and atmospheric transparency) based on years of recorded conditions at the DES site. Simulations of non-Ia type SNe are based on spectroscopically confirmed light curves that include unpublished non-Ia samples donated from the Carnegie Supernova Project (CSP), the Supernova Legacy Survey (SNLS), and the Sloan Digital Sky Survey-II (SDSS-II). We challenge scientists to run their classification algorithms and report a type for each SN. A spectroscopically confirmed subset is provided for training. The goals of this challenge are to (1) learn the relative strengths and weaknesses of the different classification algorithms, (2) use the results to improve classification algorithms, and (3) understand what spectroscopically confirmed sub-...

  13. Mathematical olympiad challenges

    CERN Document Server

    Andreescu, Titu

    2000-01-01

    Mathematical Olympiad Challenges is a rich collection of problems put together by two experienced and well-known professors and coaches of the U.S. International Mathematical Olympiad Team. Hundreds of beautiful, challenging, and instructive problems from algebra, geometry, trigonometry, combinatorics, and number theory were selected from numerous mathematical competitions and journals. An important feature of the work is the comprehensive background material provided with each grouping of problems. The problems are clustered by topic into self-contained sections with solutions provided separately. All sections start with an essay discussing basic facts and one or two representative examples. A list of carefully chosen problems follows and the reader is invited to take them on. Additionally, historical insights and asides are presented to stimulate further inquiry. The emphasis throughout is on encouraging readers to move away from routine exercises and memorized algorithms toward creative solutions to open-e...

  14. Challenges in radioecology

    International Nuclear Information System (INIS)

    Today, radioecology covers a broad scientific field; from the source to long term environmental impact from ionizing radiation. To summarize key challenges within radioecology, the present paper focuses upon knowledge gaps related to processes, mechanisms and variables contributing most to the overall uncertainties in environmental impact assessments. A series of sources related to the nuclear weapon cycle and the civil nuclear cycle has contributed, is still contributing or can potentially contribute to release of radionuclides to the environment in the future. The speciation of most radionuclides depends on the source and release conditions, and will influence ecosystem transport, biological uptake, doses and effects in flora and fauna. Radionuclides may also co-occur in contaminant mixtures (e.g., metals, organics), which potentially could lead to synergisms or antagonisms. Thus, challenges associated with the links between the source or release term - radionuclide speciation - ecosystem transfer - exposure - response relationships are highlighted.

  15. Challenges in sexual medicine

    DEFF Research Database (Denmark)

    Cellek, Selim; Giraldi, Annamaria

    2012-01-01

    The sexual medicine field has been in mode of revolution until recently. Like all other fields of biomedical research, the economic situation around the world has had a negative impact on the field's momentum-research funding bodies, regulatory bodies and pharmaceutical companies seem to have...... placed sexual medicine in their low-priority list. But this is not the only challenge the field is facing. The successful development of phosphodiesterase type 5 (PDE5) inhibitors for treatment of erectile dysfunction (ED) means that research in this area seems to have slowed. However, there remain...... several unmet medical needs within sexual medicine such as premature ejaculation, severe ED and hypoactive sexual desire disorder, which await novel therapeutic approaches. Despite these challenges, research into finding and developing such therapies is likely to continue in the sexual medicine field...

  16. Challenges to Resistance Welding

    DEFF Research Database (Denmark)

    Song, Quanfeng

    This report originates from the compulsory defense during my Ph.D. study at the Technical University of Denmark. Resistance welding is an old and well-proven technology. Yet the emergence of more and more new materials, new designs, invention off new joining techniques, and more stringent...... requirement in quality have imposed challenges to the resistance welding. More some research and development have to be done to adapt the old technology to the manufacturing industry of the 21st century. In the 1st part of the report, the challenging factors to the resistance welding are reviewed. Numerical...... simulation of resistance welding has been under development for many years. Yet it is no easy to make simulation results reliable and accurate because of the complexity of resistance welding process. In the 2nd part of the report numerical modeling of resistance welding is reviewed, some critical factors to...

  17. Bacteriophage-Derived Vectors for Targeted Cancer Gene Therapy

    Directory of Open Access Journals (Sweden)

    Md Zahidul Islam Pranjol

    2015-01-01

    Full Text Available Cancer gene therapy expanded and reached its pinnacle in research in the last decade. Both viral and non-viral vectors have entered clinical trials, and significant successes have been achieved. However, a systemic administration of a vector, illustrating safe, efficient, and targeted gene delivery to solid tumors has proven to be a major challenge. In this review, we summarize the current progress and challenges in the targeted gene therapy of cancer. Moreover, we highlight the recent developments of bacteriophage-derived vectors and their contributions in targeting cancer with therapeutic genes following systemic administration.

  18. Terabit Wireless Communication Challenges

    Science.gov (United States)

    Hwu, Shian U.

    2012-01-01

    This presentation briefly discusses a research effort on Terabit Wireless communication systems for possible space applications. Recently, terahertz (THz) technology (300-3000 GHz frequency) has attracted a great deal of interest from academia and industry. This is due to a number of interesting features of THz waves, including the nearly unlimited bandwidths available, and the non-ionizing radiation nature which does not damage human tissues and DNA with minimum health threat. Also, as millimeter-wave communication systems mature, the focus of research is, naturally, moving to the THz range. Many scientists regard THz as the last great frontier of the electromagnetic spectrum, but finding new applications outside the traditional niches of radio astronomy, Earth and planetary remote sensing, and molecular spectroscopy particularly in biomedical imaging and wireless communications has been relatively slow. Radiologists find this area of study so attractive because t-rays are non-ionizing, which suggests no harm is done to tissue or DNA. They also offer the possibility of performing spectroscopic measurements over a very wide frequency range, and can even capture signatures from liquids and solids. According to Shannon theory, the broad bandwidth of the THz frequency bands can be used for terabit-per-second (Tb/s) wireless communication systems. This enables several new applications, such as cell phones with 360 degrees autostereoscopic displays, optic-fiber replacement, and wireless Tb/s file transferring. Although THz technology could satisfy the demand for an extremely high data rate, a number of technical challenges need to be overcome before its development. This presentation provides an overview the state-of-the- art in THz wireless communication and the technical challenges for an emerging application in Terabit wireless systems. The main issue for THz wave propagation is the high atmospheric attenuation, which is dominated by water vapor absorption in the THz

  19. Energy challenges in Asia

    International Nuclear Information System (INIS)

    Energy challenges represent one of the most important security paradigms in the Asia Pacific region where you have a mixture of growing energy dependency, fuelled by high economic growth, the emergence of new major players like China and India, and a quasi-complete absence of regional regulatory mechanisms to tackle the challenges in a multilateral way. These challenges mostly concern Japan and China, where crucial energy issues are aggravated by power rivalry, historical and ideological issues, and a lack of both economic and political harmony between them. Neither countries are self sufficient in terms of energy needs. This can lead to a shared analysis and common approaches regarding Japan and China concerning this issue. Their cases are. however very different and the solutions applied are related to different world views that are not easily reconcilable. Both countries share common objectives: both want security and stable supply. But there are also big divergences and these divergences could be new sources of conflict and misunderstanding between Tokyo and Beijing. One of the main differences is history related. Both China and Japan are uneasy regarding outside energy dependency. In Japan, memories of the pre-war oil embargo have not disappeared. The oil shocks of the 70's renewed this uneasiness. However, Japan's outside dependency is not new. Tokyo has learned to live with it, finding a system to alleviate this vulnerability in cooperation with its partners, multilateral institutions like the International Energy Agency (IEA). China's outside dependency is new. The country's dependency on oil, which began in 1993, is particularly challenging since the principles of independence, non interference and military autonomy, principles at the core of Maoist foreign strategy, did not completely disappear in spite of China's new policy of reform and opening up. China's leadership, even the fourth generation, did not forget its isolation during the 60's and 70's

  20. Librarianship: A Challenging Profession

    OpenAIRE

    Lalithabai, K K.

    1996-01-01

    Defines librarianship as the art and science of managing recorded knowledge. Observes that in earlier days when the recorded sources of information were limited in number, scholars could be the users as well as managers of libraries. But today’s libraries with torrents of information sources and users on either side makes management a truly challenging task requiring highly specialized knowledge and training in the sophisticated techniques of information handling. Views that in information co...

  1. PHARMACOVIGILANCE: BARRIERS AND CHALLENGES

    OpenAIRE

    Varma, S. K.; RAPELLIWAR A; S. Sutradhar; THAWARE P; Misra, A. K.

    2013-01-01

    Pharmacovigilance is a new discipline which deals with adverse drug or any drug related problems. Pharmacovigilance programme was not bed of roses but its path is laid with challenges and barriers. It is facing obstacles from deficiency from professional health personal to web-based sale of drugs, counterfeit drug to self-medication, etc. It is an integral part of the health sector and identification and reporting of adverse drug effects will have a positive impact on the public health. Impro...

  2. CHALLENGES FOR FOREIGN TEACHERS

    Institute of Scientific and Technical Information of China (English)

    DengJing

    2004-01-01

    The learner differences and contrasts between the two cultures involved are important aspects that influence foreign language teaching and learning. The foreign teacher as an outsider of the learner's native culture, inevitably faces quite a few challenges. With the focus on the self-esteem, character types, and motivation of the learner, the paper analyses how these factors influence the foreign teacher's teaching. Relevant solutions are also proposed.

  3. Challenges in Crowd Simulation

    OpenAIRE

    Thalmann, Daniel; Grillon, Helena; Maim, Jonathan; Yersin, Barbara

    2009-01-01

    The purpose of this paper is to identify the problems to solve in order to simulate real-time crowds in a Virtual Environment. We try to classify these problems and study how they have been addressed until now by the research community and our Lab in particular. We then discuss for each problem what are the,future challenges and how to address them.

  4. The First Provenance Challenge

    OpenAIRE

    Moreau, Luc; Ludaescher, Bertram; Altintas, Ilkay; Barga, Roger S.; Bowers, Shawn; Callahan, Steven; Chin Jr., George; Clifford, Ben; Cohen, Shirley; Cohen-Boulakia, Sarah; Davidson, Susan; Deelman, Ewa; Digiampietri, Luciano; Foster, Ian; Freire, Juliana

    2008-01-01

    The first Provenance Challenge was set up in order to provide a forum for the community to help understand the capabilities of different provenance systems and the expressiveness of their provenance representations. To this end, a Functional Magnetic Resonance Imaging workflow was defined, which participants had to either simulate or run in order to produce some provenance representation, from which a set of identified queries had to be implemented and executed. Sixteen teams responded to the...

  5. South China Sea Challenge

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    China's attempts to solve disputes with ASEAN over the South China Sea help regional peace China's marine economy and security are currently faced with new challenges, requiring careful handling, especially in disputes with ASEAN countries and in promoting common development of the South China Sea. The outcome of how this is dealt with could undoubtedly pave the way for solutions to other oceanic disputes. The South China Sea is located south of

  6. Public budgets: New challenges

    OpenAIRE

    Attila, György

    2010-01-01

    Budgeting is passing through changes all over the world in order to find more efficient ways to guide public money usage. The last half of century gave us multiple examples of how to improve budgetary performance, but there are a lot to do in next decades to accomplish this goal. The challenges regarding public budgeting are: using accrual based budgeting, use performance information to determine the allocations for each agency, and strengthening the budgetary transparency.

  7. Sustainability challenges and trends

    OpenAIRE

    De Ridder, M.

    2011-01-01

    In the coming decades, increases in population, income and health will put additional pressures on our planet’s biosphere. To meet the needs of future generations, we need to adapt our ways of living and definitions of economic development. A transition to a more sustainable world is imperative if we want to stop depleting the Earth’s resources more quickly than it can regenerate them. This paper synthesizes current trends and challenges that are relevant for the policy debate on sustainabili...

  8. ATLAS Data Challenge 1

    CERN Document Server

    DC1 TaskForce

    2003-01-01

    The ATLAS Collaboration at CERN is preparing for the data taking and analysis at LHC that will start in 2007. Therefore, in 2002 a series of Data Challenges (DC's) was started whose goals are the validation of the Computing Model, of the complete software suite, of the data model, and to ensure the correctness of the technical choices to be made. A major feature of the first Data Challenge (DC1) was the preparation and the deployment of the software required for the production of large event samples for the High Level Trigger and Physics communities, and the production of those large data samples as a worldwide distributed activity. It should be noted that it was not an option to "run everything at CERN" even if we had wanted to; the resources were not available at CERN to carry out the production on a reasonable time-scale. We were therefore faced with the great challenge of organising and then carrying out this large-scale production at a significant number of sites around the world. However, the benefits o...

  9. IDEOLOGICALLY CHALLENGING ENTERTAINMENT (ICE

    Directory of Open Access Journals (Sweden)

    Dana Lori Chalmers

    2015-09-01

    Full Text Available Ideologically Challenging Entertainment (ICE is entertainment that challenges ‘us vs. them’ ideologies associated with radicalization, violent conflict and terrorism. ICE presents multiple perspectives on a conflict through mainstream entertainment. This article introduces the theoretical underpinnings of ICE, the first ICE production and the audience responses to it. The first ICE production was Two Merchants: The Merchant of Venice adapted to challenge ideologies of the Arab-Israeli Conflict. A mixed-methods study of audience responses explored whether this production inspired audiences to shift their ideological views. Each performance included two versions of the adaptation: a Jewish dominated society with an Arab Muslim minority, contrasted with an Arab Muslim dominated society and a Jewish minority. A mixed-methods study of audience responses explored whether this production inspired audiences to shift their ideological views to become more tolerant of differences away from ideological radicalization. Of audience members who did not initially agree with the premise of the production, 40% reconsidered their ideological views, indicating increased tolerance, greater awareness of and desire to change their own prejudices. In addition, 86% of the audience expressed their intention to discuss the production with others, thereby encouraging critical engagement with, and broader dissemination of the message. These outcomes suggest that high quality entertainment – as defined by audience responses to it - can become a powerful tool in the struggle against radicalised ideologies.

  10. Comparative Proteomic Profiling of Mycobacterium bovis and BCG Vaccine Strains

    KAUST Repository

    Gao, Ge

    2013-09-01

    BCG is the only licensed human vaccine currently available against TB. Derived from a virulent strain of M. bovis, the vaccine was thought to have struck a balance between reduced virulence and preserved immunogenicity. Nowadays, BCG vaccine strains used in different countries and vaccination programs show clear variations in their genomes and immune protective properties. The aim of this study was to characterize the proteomic profile on Mycobacterium bovis and five BCG strains Pasteur, Tokyo, Danish, Phipps and Birkhaug by Tandem Mass Tag® (TMT®)-labeling quantitative proteomic approach. In total, 420 proteins were identified and 377 of them were quantitated for their relative abundance. We reported the number and relationship of differential expressed proteins in BCG strains compared to M. bovis and investigated their functions by bioinformatics analysis. Several interesting up-regulated and down-regulated protein targets were found. The identified proteins and their quantitative expression profiles provide a basis for further understanding of the cellular biology of M. bovis and BCG vaccine strains, and hopefully would assist in the design of better anti-TB vaccine and drugs.

  11. Development of a Strain-Specific Real-Time PCR Assay for Enumeration of a Probiotic Lactobacillus reuteri in Chicken Feed and Intestine

    OpenAIRE

    Sattler, Verity Ann; Mohnl, Michaela; Klose, Viviana

    2014-01-01

    A strain-specific real-time PCR assay was developed for quantification of a probiotic Lactobacillus reuteri (DSM 16350) in poultry feed and intestine. The specific primers were designed based on a genomic sequence of the strain derived from suppression subtractive hybridization with the type strain L. reuteri DSM 20016. Specificity was tested using a set of non-target strains from several sources. Applicability of the real-time PCR assay was evaluated in a controlled broiler feeding trial by ...

  12. PRICE-LEVEL TARGETING – A VIABLE ALTERNATIVE TO INFLATION TARGETING?

    Directory of Open Access Journals (Sweden)

    Iulian Vasile Popescu

    2012-12-01

    Full Text Available The recent financial crisis that has led some central banks reaching the zero lower bound of their interest rate to use unconventional monetary policy instruments, has brought to the forefront theacademic discussions on the shift from inflation targeting (IT to price level targeting. This paper provides a comparative analysis on IT strategy and targeting the price level, assesses the implications and highlights the challenges of an eventual transition to a new monetary policy strategy. Balancing the advantages (mainly better anchored inflation expectations and disadvantages (communication difficulties generated by following a potential price-level targeting strategy and the necessary prerequisites for its functionality (predictive agents, fully familiar with the implications of such a strategy and with complete confidence in themonetary authority has led us to the conclusion that there is no common acceptance that price level targeting strategy might replace the present IT framework.

  13. Gastroparesis: Concepts, Controversies, and Challenges

    Directory of Open Access Journals (Sweden)

    Klaus Bielefeldt

    2012-01-01

    Full Text Available Patients with gastroparesis often present a challenge to the treating physician. Postprandial symptoms with nausea and vomiting may not only lead to nutritional and metabolic consequences, but also cause significant disruptions to social activities that often center around food. While the definition of gastroparesis focuses on impaired gastric emptying, treatment options that affect gastric function are limited and often disappointing. The female predominance, the mostly idiopathic nature of the illness with a common history of abuse, and coexisting anxiety or depression show parallels with other functional disorders of the gastrointestinal tract. These parallels provided the rationale for some initial studies investigating alternative therapies that target the brain rather than the stomach. This emerging shift in medical therapy comes at a time when clinical studies suggest that gastric electrical stimulation may exert its effects by modulating visceral sensory processing rather than altering gastric motility. Physiologic and detailed anatomic investigations also support a more complex picture with different disease mechanisms, ranging from impaired accommodation to apparent visceral hypersensitivity or decreased interstitial cells of Cajal to inflammatory infiltration of myenteric ganglia. Delayed gastric emptying remains the endophenotype defining gastroparesis. However, our treatment options go beyond prokinetics and may allow us to improve the quality of life of affected individuals.

  14. Improved Gene Targeting through Cell Cycle Synchronization.

    Directory of Open Access Journals (Sweden)

    Vasiliki Tsakraklides

    Full Text Available Gene targeting is a challenge in organisms where non-homologous end-joining is the predominant form of recombination. We show that cell division cycle synchronization can be applied to significantly increase the rate of homologous recombination during transformation. Using hydroxyurea-mediated cell cycle arrest, we obtained improved gene targeting rates in Yarrowia lipolytica, Arxula adeninivorans, Saccharomyces cerevisiae, Kluyveromyces lactis and Pichia pastoris demonstrating the broad applicability of the method. Hydroxyurea treatment enriches for S-phase cells that are active in homologous recombination and enables previously unattainable genomic modifications.

  15. Genome Sequence of Pseudomonas chlororaphis Strain 189

    Science.gov (United States)

    Town, Jennifer; Audy, Patrice; Boyetchko, Susan M.

    2016-01-01

    Pseudomonas chlororaphis strain 189 is a potent inhibitor of the growth of the potato pathogen Phytophthora infestans. We determined the complete, finished sequence of the 6.8-Mbp genome of this strain, consisting of a single contiguous molecule. Strain 189 is closely related to previously sequenced strains of P. chlororaphis. PMID:27340063

  16. Comparative Proteomic Analyses of Avirulent, Virulent, and Clinical Strains of Mycobacterium tuberculosis Identify Strain-specific Patterns.

    Science.gov (United States)

    Jhingan, Gagan Deep; Kumari, Sangeeta; Jamwal, Shilpa V; Kalam, Haroon; Arora, Divya; Jain, Neharika; Kumaar, Lakshmi Krishna; Samal, Areejit; Rao, Kanury V S; Kumar, Dhiraj; Nandicoori, Vinay Kumar

    2016-07-01

    Mycobacterium tuberculosis is an adaptable intracellular pathogen, existing in both dormant as well as active disease-causing states. Here, we report systematic proteomic analyses of four strains, H37Ra, H37Rv, and clinical isolates BND and JAL, to determine the differences in protein expression patterns that contribute to their virulence and drug resistance. Resolution of lysates of the four strains by liquid chromatography, coupled to mass spectrometry analysis, identified a total of 2161 protein groups covering ∼54% of the predicted M. tuberculosis proteome. Label-free quantification analysis of the data revealed 257 differentially expressed protein groups. The differentially expressed protein groups could be classified into seven K-means cluster bins, which broadly delineated strain-specific variations. Analysis of the data for possible mechanisms responsible for drug resistance phenotype of JAL suggested that it could be due to a combination of overexpression of proteins implicated in drug resistance and the other factors. Expression pattern analyses of transcription factors and their downstream targets demonstrated substantial differential modulation in JAL, suggesting a complex regulatory mechanism. Results showed distinct variations in the protein expression patterns of Esx and mce1 operon proteins in JAL and BND strains, respectively. Abrogating higher levels of ESAT6, an important Esx protein known to be critical for virulence, in the JAL strain diminished its virulence, although it had marginal impact on the other strains. Taken together, this study reveals that strain-specific variations in protein expression patterns have a meaningful impact on the biology of the pathogen. PMID:27151218

  17. Strain Growth in Containment Vessels

    Institute of Scientific and Technical Information of China (English)

    DONG Q; LI Q M; ZHENG J Y

    2006-01-01

    Strain growth is a phenomenon observed in containment vessels subjected to internal blast loading.The elastic response of the vessel may become larger in a later stage compared to its response during the initial stage.The dynamic responses of infinitely long cylindrical containment vessels subjected to uniformly-distributed internal blast loading are studied using LS-DYNA.The development of bending modes and the interaction between the breathing mode and bending modes are observed.The methodology developed for dynamic elastic buckling analysis is employed to study the strain growth phenomenon in explosion containment vessels.It is shown that the dynamic instable vibration of a containment vessel is the basic mechanism of strain growth.

  18. Thermoelectric properties of strained silicon

    Energy Technology Data Exchange (ETDEWEB)

    Hinsche, Nicki F.; Zahn, Peter [Martin-Luther-Universitaet, Institut fuer Physik, Von-Seckendorff-Platz 1, 06120 Halle/S. (Germany); Mertig, Ingrid [Martin-Luther-Universitaet, Institut fuer Physik, Von-Seckendorff-Platz 1, 06120 Halle/S. (Germany); Max-Planck-Institut fuer Mikrostrukturphysik, Weinberg 2, D-06120 Halle (Germany)

    2011-07-01

    Starting from bulk silicon, we study the change in thermoelectric properties due to symmetry breaking in rolled-up and layered Si which might lead to nanostructured thermoelectrics. Valley splitting in strained Si caused by tetragonal distortion was studied recently with respect to the enhancement of electron mobility. Our results show that the tetragonal distortion has a strong influence on the electronic transport properties. The electronic structure is calculated self consistently within the framework of density functional theory. The transport properties are studied in the diffusive limit applying the Boltzmann theory in relaxation time approximation. In detail, the anisotropy of the electrical conductivity, the thermopower and the resulting powerfactor in the in-plane and off-plane directions are studied in dependence on strain, doping level and temperature. It is shown, that the powerfactor at a given temperature can be enhanced slightly by strain for p-doping, while no enhancement is obtained for n-doping.

  19. Proteção fetal frente a desafio com o vírus da Diarréia Viral Bovina (BVDV em ovelhas imunizadas com duas amostras de vírus modificadas experimentalmente Fetal protection against challenge with bovine viral diarrhea virus (BVDV in pregnant ewes immunized with two strains experimentally attenuated

    Directory of Open Access Journals (Sweden)

    Mário C.S. Brum

    2002-04-01

    virus (BVDV submitted to multiple passages in tissue culture associated with ultraviolet irradiation were evaluated as vaccine virus candidates. The attenuation of the modified viruses was assessed in calves and in pregnant ewes. Intramuscular inoculation of the viruses in four seronegative calves produced only a mild and transient rise in body temperature, followed by the production of high titers of neutralizing antibodies. The viruses were not detected in nasal secretions or in the blood following inoculation. However, intramuscular inoculation of these viruses in four pregnant ewes resulted in transplacental transmission and infection of all fetuses. To assess fetal protection conferred by immunization, pregnant ewes immunized twice with the modified viruses were subsequently challenged by intranasal inoculation of BVDV-1 (SV-126.8, n=6 or BVDV-2 (SV-260, n=5. At the day of challenge (134 days after the second immunization, all ewes had high titers of neutralizing antibodies (256 to >4096 to the vaccine viruses and variable titers (8 to >4096 to Brazilian BVDV-1 and BVDV-2 field isolates. Fifteen days after challenge, the ewes were euthanized and fetal tissues were examined for infectivity. All fetuses from non-vaccinated, challenged ewes (n=4 were infected. In contrast, none of the fetuses from the immunized dams (n=11 were positive for virus, indicating that the immunological response induced by immunization with the vaccine candidate viruses was capable of preventing fetal infection. These results indicate that it is possible to achieve fetal protection to BVDV by induction of a strong immunological response using modified live vaccines.

  20. Spin transport in graphene superlattice under strain

    Science.gov (United States)

    Sattari, Farhad

    2016-09-01

    In this paper, the spin-dependent transport and the spin polarization properties for graphene superlattice with Rashba spin-orbit interaction (RSOI) in the presence of zigzag and armchair direction strain are studied. It is found that for the zigzag direction strain the angular range of the spin-inversion can be efficiently controlled by the strain strength. In addition, the efficiency of spin-inversion and spin-dependent conductivity decreases by increasing the strain strength. When the armchair direction strain is applied to a monolayer graphene superlattice the spin polarization can be observed and increases by increasing the strain strength, whereas for the zigzag direction strain it is zero.