WorldWideScience

Sample records for challenging strain targeting

  1. 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 immunity...

  2. The challenge of targeting metastasis.

    Science.gov (United States)

    Fidler, Isaiah J; Kripke, Margaret L

    2015-12-01

    Metastases that are resistant to conventional therapy are the major cause of death from cancer. In most patients, metastasis has already occurred by the time of diagnosis. Thus, the prevention of metastasis is unlikely to be of therapeutic benefit. The biological heterogeneity of metastases presents a major obstacle to treatment. However, the growth and survival of metastases depend on interactions between tumor cells and host homeostatic mechanisms. Targeting these interactions, in addition to the tumor cells, can produce synergistic therapeutic effects against existing metastases.

  3. Evaluation of dengue virus strains for human challenge studies.

    Science.gov (United States)

    Mammen, M P; Lyons, A; Innis, B L; Sun, W; McKinney, D; Chung, R C Y; Eckels, K H; Putnak, R; Kanesa-thasan, N; Scherer, J M; Statler, J; Asher, L V; Thomas, S J; Vaughn, D W

    2014-03-14

    Discordance between the measured levels of dengue virus neutralizing antibody and clinical outcomes in the first-ever efficacy study of a dengue tetravalent vaccine (Lancet, Nov 2012) suggests a need to re-evaluate the process of pre-screening dengue vaccine candidates to better predict clinical benefit prior to large-scale vaccine trials. In the absence of a reliable animal model and established correlates of protection for dengue, a human dengue virus challenge model may provide an approach to down-select vaccine candidates based on their ability to reduce risk of illness following dengue virus challenge. We report here the challenge of flavivirus-naïve adults with cell culture-passaged dengue viruses (DENV) in a controlled setting that resulted in uncomplicated dengue fever (DF). This sets the stage for proof-of-concept efficacy studies that allow the evaluation of dengue vaccine candidates in healthy adult volunteers using qualified DENV challenge strains well before they reach field efficacy trials involving children. Fifteen flavivirus-naïve adult volunteers received 1 of 7 DENV challenge strains (n=12) or placebo (n=3). Of the twelve volunteers who received challenge strains, five (two DENV-1 45AZ5 and three DENV-3 CH53489 cl24/28 recipients) developed DF, prospectively defined as ≥2 typical symptoms, ≥48h of sustained fever (>100.4°F) and concurrent viremia. Based on our study and historical data, we conclude that the DENV-1 and DENV-3 strains can be advanced as human challenge strains. Both of the DENV-2 strains and one DENV-4 strain failed to meet the protocol case definition of DF. The other two DENV-4 strains require additional testing as the illness approximated but did not satisfy the case definition of DF. Three volunteers exhibited effusions (1 pleural/ascites, 2 pericardial) and 1 volunteer exhibited features of dengue (rash, lymphadenopathy, neutropenia and thrombocytopenia), though in the absence of fever and symptoms. The occurrence of

  4. SMET: systematic multiple enzyme targeting - a method to rationally design optimal strains for target chemical overproduction.

    Science.gov (United States)

    Flowers, David; Thompson, R Adam; Birdwell, Douglas; Wang, Tsewei; Trinh, Cong T

    2013-05-01

    Identifying multiple enzyme targets for metabolic engineering is very critical for redirecting cellular metabolism to achieve desirable phenotypes, e.g., overproduction of a target chemical. The challenge is to determine which enzymes and how much of these enzymes should be manipulated by adding, deleting, under-, and/or over-expressing associated genes. In this study, we report the development of a systematic multiple enzyme targeting method (SMET), to rationally design optimal strains for target chemical overproduction. The SMET method combines both elementary mode analysis and ensemble metabolic modeling to derive SMET metrics including l-values and c-values that can identify rate-limiting reaction steps and suggest which enzymes and how much of these enzymes to manipulate to enhance product yields, titers, and productivities. We illustrated, tested, and validated the SMET method by analyzing two networks, a simple network for concept demonstration and an Escherichia coli metabolic network for aromatic amino acid overproduction. The SMET method could systematically predict simultaneous multiple enzyme targets and their optimized expression levels, consistent with experimental data from the literature, without performing an iterative sequence of single-enzyme perturbation. The SMET method was much more efficient and effective than single-enzyme perturbation in terms of computation time and finding improved solutions.

  5. Targeting: the challenges of modern warfare

    NARCIS (Netherlands)

    Ducheine, P.A.L.; Schmitt, M.N.; Osinga, F.P.B.

    2016-01-01

    This book offers a multidisciplinary treatment of targeting. It is intended for use by the military, government legal advisers and academics. The book is suitable for use in both military training and educational programs and in Bachelor and Master degree level courses on such topics as War Studies

  6. Uncertainties, monetary policy and financial stability: challenges on inflation targeting

    Directory of Open Access Journals (Sweden)

    Gabriel Caldas Montes

    2010-03-01

    Full Text Available This work aims at presenting the challenges that inflation targeting central banks may face since uncertainties represent a harmful element for the effectiveness of monetary policy, and since financial instabilities may disturb the transmission mechanisms - in particular, the expectation channel - and thus the economic stability. Financial stability must not be considered as a simple goal of monetary policy, but a precondition for central banks operate their policies and reach the goals of inflation and output stability. The work identifies different sources of uncertainties that surround central banks' decisions; and approaches the role that inflation targeting central banks should play according to some basic principles that can serve as useful guides for central banks to help them achieve successful outcomes in their conduct of monetary policy.

  7. 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

  8. Dendritic cell targeted vaccines: Recent progresses and challenges.

    Science.gov (United States)

    Chen, Pengfei; Liu, Xinsheng; Sun, Yuefeng; Zhou, Peng; Wang, Yonglu; Zhang, Yongguang

    2016-03-01

    Dendritic cells (DCs) are known to be a set of morphology, structure and function of heterogeneous professional antigen presenting cells (APCs), as well as the strongest functional antigen presenting cells, which can absorb, process and present antigens. As the key regulators of innate and adaptive immune responses, DCs are at the center of the immune system and capable of interacting with both B cells and T cells, thereby manipulating the humoral and cellular immune responses. DCs provide an essential link between the innate and adaptive immunity, and the strong immune activation function of DCs and their properties of natural adjuvants, make them a valuable target for antigen delivery. Targeting antigens to DC-specific endocytic receptors in combination with the relevant antibodies or ligands along with immunostimulatory adjuvants has been recently recognized as a promising strategy for designing an effective vaccine that elicits a strong and durable T cell response against intracellular pathogens and cancer. This opinion article provides a brief summary of the rationales, superiorities and challenges of existing DC-targeting approaches.

  9. Strain-Specific Changes in Locomotor Behavior in Larval Zebrafish Elicited by Cholinergic Challenge

    Science.gov (United States)

    Some studies have compared the baseline behavior of different strains of larval zebrafish (Danio rerio), but there is sparse information on strain-specific responses to chemical challenges. The following study examines both the basal activity and response to a pharmacological cha...

  10. Full-field dynamic strain prediction on a wind turbine using displacements of optical targets measured by stereophotogrammetry

    Science.gov (United States)

    Baqersad, Javad; Niezrecki, Christopher; Avitabile, Peter

    2015-10-01

    Health monitoring of rotating structures (e.g. wind turbines and helicopter blades) has historically been a challenge due to sensing and data transmission problems. Unfortunately mechanical failure in many structures initiates at components on or inside the structure where there is no sensor located to predict the failure. In this paper, a wind turbine was mounted with a semi-built-in configuration and was excited using a mechanical shaker. A series of optical targets was distributed along the blades and the fixture and the displacement of those targets during excitation was measured using a pair of high speed cameras. Measured displacements with three dimensional point tracking were transformed to all finite element degrees of freedom using a modal expansion algorithm. The expanded displacements were applied to the finite element model to predict the full-field dynamic strain on the surface of the structure as well as within the interior points. To validate the methodology of dynamic strain prediction, the predicted strain was compared to measured strain by using six mounted strain-gages. To verify if a simpler model of the turbine can be used for the expansion, the expansion process was performed both by using the modes of the entire turbine and modes of a single cantilever blade. The results indicate that the expansion approach can accurately predict the strain throughout the turbine blades from displacements measured by using stereophotogrammetry.

  11. 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.

  12. Development of a systematic feedback isolation approach for targeted strains from mixed culture systems.

    Science.gov (United States)

    Poudel, Pramod; Tashiro, Yukihiro; Miyamoto, Hirokuni; Miyamoto, Hisashi; Okugawa, Yuki; Sakai, Kenji

    2017-01-01

    Elucidation of functions of bacteria in a mixed culture system (MCS) such as composting, activated sludge system is difficult, since the system is complicating with many unisolated bacteria. Here, we developed a systematic feedback isolation strategy for the isolation and rapid screening of multiple targeted strains from MCS. Six major strains (Corynebacterium sphenisci, Bacillus thermocloacae, Bacillus thermoamylovorans, Bacillus smithii, Bacillus humi, and Bacillus coagulans), which are detected by denaturing gradient gel electrophoresis (DGGE) analysis in our previous study on MCS for l-lactic acid production, were targeted for isolation. Based on information of suitable cultivation conditions (e.g., media, pH, temperature) from the literature, feedback isolation was performed to form 136 colonies. The following direct colony matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was optimised as the second screening to narrow down 20 candidate colonies from similar spectra patterns with six closest type strains. This step could distinguish bacteria at the species level with distance similarity scores ≥0.55 corresponding to 16S rRNA gene sequence similarity ≥98.2%, suggesting that this is an effective technique to minimize isolates close to targeted type strains. Analysis of 16S rRNA gene sequences indicated that two targeted strains and one strain related to the target had successfully been isolated, showing high similarities (99.5-100%) with the sequences from the DGGE bands, and that the other candidates were affiliated with three strains that were closely related to the target species. This study proposes a new method for systematic feedback isolation that may be useful for isolating targeted strains from MCS for further investigation.

  13. Strain Measurement for Hollow Projectiles During Its Penetration of Concrete Targets

    Institute of Scientific and Technical Information of China (English)

    王琳; 王富耻; 王鲁; 李树奎

    2004-01-01

    Gives a new technique to measure the dynic deformation behavior and strain development of a hollow steel projectile during its penetration of concrete targets. Direct strain measurement was performed by applying strain gages attached to the inner walls of the hollow projectile, linked with on-board testing and storage recorder. This on-board test-record system is easy to operate, cost-effective and can provide reasonable, accurate and detailed information. Obverse ballistic experiments were carried out on ogival-nose hollow projectiles normally impacting concrete targets at velocities from 150 m/s to 300 m/s. The deformation process of projectiles was measured, recorded and played back. Profiles of voltage-time relationship were successively obtained and transfered to strain-time relationship with the aid of calibration tables. It was found that projectiles go through a series of compression and tension deformations intermittently. Relationships between strain development and projectile deformation process were discussed.

  14. Carcinoembryonic antigens are targeted by diverse strains of typable and non-typable Haemophilus influenzae.

    Science.gov (United States)

    Virji, M; Evans, D; Griffith, J; Hill, D; Serino, L; Hadfield, A; Watt, S M

    2000-05-01

    Haemophilus influenzae (Hi), a commensal of the human respiratory mucosa, is an important cause of localized and systemic infections. We show that distinct strains belonging to typable (THi) and non-typable (NTHi) H. influenzae target human carcinoembryonic antigens (the membrane associated CEA family of cell adhesion molecules, are now termed CEACAMs). All strains of H. influenzae biogroup aegyptius (Hi-aeg) and more than 70% of THi and NTHi strains tested specifically recognize CEACAMI-Fc soluble constructs. Furthermore, transfection of Chinese hamster ovary cells with human CEACAM1 cDNA alone was sufficient for promoting Hi interactions with the transfected cells. The majority of the Hi-aeg strains tested interacted with soluble constructs containing only the N-terminal domain. In contrast, several THi and NTHi strains reacted with soluble constructs only when additional extracellular A and B domains of the receptor were present. The use of monoclonal antibodies confirmed that THi and NTHi strains also interact primarily at the N-domain. We used site-directed mutants of CEACAM1 that contained substitutions at surface exposed amino acids and a molecular model of the N-domain to identify the residues involved in interactions with Hi ligands. The studies show that a common region exposed at the CFG face of the molecule is targeted by diverse Hi strains. However, mutation at distinct sites within this area affected the interactions of distinct strains signifying the potential for tissue tropism via this receptor. Analyses of the molecular basis of interaction with human cell lines and purified CEA show that Hi strains, especially those belonging to Hi-aeg, interact with multiple CEACAMs. Because Neisseria meningitidis (Nm) strains are also known to bind at the CFG face of the receptor, we used Nm and Hi strains in co-infection experiments and demonstrate competition between these mucosal pathogens in colonization of target cells via CEACAMs.

  15. Challenges to increasing targeting efficiency in genome engineering.

    Science.gov (United States)

    Horii, Takuro; Hatada, Izuho

    2016-01-01

    Gene targeting technologies are essential for the analysis of gene functions. Knockout mouse generation via genetic modification of embryonic stem cells (ESCs) is the commonest example, but it is a time-consuming and labor-intensive procedure. Recently, a novel genome editing technology called CRISPR/Cas has enabled the direct production of knockout mice by non-homologous end joining (NHEJ)-mediated mutations. Unexpectedly, however, it generally exhibits a low efficiency in homologous recombination (HR) and is prone to high mosaicism. Meanwhile, gene targeting using ESCs is still being improved, as reported by Fukuda et al. in this issue. Here, we outline current gene targeting technologies with special emphasis on HR-mediated technologies, which are currently being performed using these two major strategies.

  16. 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.

  17. 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.

  18. 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.

  19. Detailed analysis of an experimental challenge model for Leishmania infantum (JPC strain) in dogs.

    Science.gov (United States)

    Poot, Jacqueline; Rogers, Matthew E; Bates, Paul A; Vermeulen, Arno

    2005-06-10

    In this study, disease progression after intravenous or subdermal infection of dogs with Leishmania infantum JPC strain was monitored. A challenge performed on 14 dogs via the intravenous route with 5 x 10(7) stationary phase promastigotes of the L. infantum JPC strain was 100% successful. During a follow up period of 1.5 years, several parameters were evaluated in order to find the most reliable disease markers. Parasite detection by culture and histology were found to be very sensitive (100%). Additionally, regular physical examination, serology and serum gamma-globulin levels were found to be useful parameters in the evaluation of disease severity and are recommended for inclusion in vaccination-challenge experiments. Although this intravenous challenge model has practical limitations, the data set confirms it is the best experimental model currently available for vaccine development. Two intravenously infected dogs were treated with corticosteroids for 5 months. This treatment was shown to enhance all aspects of a Leishmania infection. Five more dogs were infected by sub-dermal injection of promastigotes mixed with a proteophosphoglycan-matrix (PSG) secreted by Leishmania that assists in transmission and infection by sand fly bite. The resulting parasite burdens were low and the animals remained asymptomatic during a 2-year follow up period. However, this procedure did result in infection in 80% of the dogs and is appealing for future development as a natural challenge model in vaccine development.

  20. Liver-targeted gene therapy: Approaches and challenges.

    Science.gov (United States)

    Aravalli, Rajagopal N; Belcher, John D; Steer, Clifford J

    2015-06-01

    The liver plays a major role in many inherited and acquired genetic disorders. It is also the site for the treatment of certain inborn errors of metabolism that do not directly cause injury to the liver. The advancement of nucleic acid-based therapies for liver maladies has been severely limited because of the myriad untoward side effects and methodological limitations. To address these issues, research efforts in recent years have been intensified toward the development of targeted gene approaches using novel genetic tools, such as zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats as well as various nonviral vectors such as Sleeping Beauty transposons, PiggyBac transposons, and PhiC31 integrase. Although each of these methods uses a distinct mechanism of gene modification, all of them are dependent on the efficient delivery of DNA and RNA molecules into the cell. This review provides an overview of current and emerging therapeutic strategies for liver-targeted gene therapy and gene repair.

  1. Laser heating challenges of high yield MagLIF targets

    Science.gov (United States)

    Slutz, Stephen; Sefkow, Adam; Vesey, Roger

    2014-10-01

    The MagLIF (Magnetized Liner Inertial Fusion) concept is predicted by numerical simulation to produce fusion yields of about 100 kJ, when driven by 25 MA from the existing Z accelerator [S. A. Slutz et al. Phys. Plasmas 17, 056303 (2010)] and much higher yields with future accelerators delivering higher currents [Slutz and Vesey PRL 108, 025003 (2012)]. The fuel must be heated before compression to obtain significant fusion yields due to the relatively slow implosion velocities (~ 100 km/s) of magnetically driven liners. Lasers provide a convenient means to accomplish this pre-compressional heating of the fusion fuel, but there are challenges. The laser must penetrate a foil covering the laser entrance hole and deposit 20-30 kJ within the ~1 cm length of the liner in fuel at 6-12 mg/cc. Such high densities could result in beam scattering due to refraction and laser plasma interactions. Numerical simulations of the laser heating process are presented, which indicate that energies as high as 30 kJ could be deposited in the fuel by using two laser pulses of different wavelengths. Simulations of this process will be presented as well of results for a MagLIF design for a potential new machine delivering 50 MA of current. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy's National Nuclear Security Administration under Contract DE-AC04-94AL85000.

  2. Metabolomics as a tool for target identification in strain improvement: The influence of phenotype definition

    NARCIS (Netherlands)

    Braaksma, M.; Bijlsma, S.; Coulier, L.; Punt, P.J.; Werf, M.J. van der

    2011-01-01

    For the optimization of microbial production processes, the choice of the quantitative phenotype to be optimized is crucial. For instance, for the optimization of product formation, either product concentration or productivity can be pursued, potentially resulting in different targets for strain imp

  3. A dual-strain feline calicivirus vaccine stimulates broader cross-neutralization antibodies than a single-strain vaccine and lessens clinical signs in vaccinated cats when challenged with a homologous feline calicivirus strain associated with virulent systemic disease.

    Science.gov (United States)

    Huang, Chengjin; Hess, Jennifer; Gill, Michael; Hustead, David

    2010-02-01

    Feline calicivirus (FCV) causes an array of clinical disease in cats. Traditionally this disease has been associated with respiratory disease, limping, or chronic stomatitis. Within the last 10 years, virulent systemic feline calicivirus (VS-FCV) has been recognized which causes additional clinical signs and has a higher fatality rate. A dual-strain FCV vaccine containing a strain of FCV associated with traditional respiratory disease and a VS-FCV strain stimulates serum cross-neutralization antibodies when tested against field strains from Europe and VS-FCV strains from USA. Following challenge with a homologous VS-FCV strain, vaccinated cats had significantly reduced clinical signs.

  4. Evolution of targeted therapies in cancer: opportunities and challenges in the clinic.

    Science.gov (United States)

    Santhosh, Sam; Kumar, Prasanna; Ramprasad, Vedam; Chaudhuri, Amitabha

    2015-01-01

    Targeted therapies have changed the course of cancer treatment in recent years. By reducing toxicity and improving outcome, these new generations of precision medicines have extended patient lives beyond what could be achieved by the use of nontargeted therapies. In the last 2 years, several new molecular entities targeting signaling proteins and immune pathways have gone through successful clinical development resulting in their approval. These new targeted therapies require patient selection and the discovery of biomarkers of response. This review discusses the evolution of targeted therapies in cancer and challenges in translating the concepts into clinical practice.

  5. 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.

  6. Monetary Policy Challenges - Inflation Targeting Strategy and the Process of Euro Adoption

    Directory of Open Access Journals (Sweden)

    Adina Criste

    2009-06-01

    Full Text Available This paper is a review of some of the challenges for the monetary authorities in countries whichadopted an inflation targeting strategy, and which are also intending to adopt Euro. Both the increasingmobility of capital flows and the preparations for entering ERM II are constraints for such a monetarystrategy. Since September 2008, the financial crisis, having burst into the developed countries, has alsoaffected the Central and Eastern Europe countries, and this phenomenon represents another challenge for themonetary authorities.

  7. Targeting bacterial topoisomerase I to meet the challenge of finding new antibiotics.

    Science.gov (United States)

    Tse-Dinh, Yuk-Ching

    2015-01-01

    Resistance of bacterial pathogens to current antibiotics has grown to be an urgent crisis. Approaches to overcome this challenge include identification of novel targets for discovery of new antibiotics. Bacterial topoisomerase I is present in all bacterial pathogens as a potential target for bactericidal topoisomerase poison inhibitors. Recent efforts have identified inhibitors of bacterial topoisomerase I with antibacterial activity. Additional research on the mode of action and binding site of these inhibitors would provide further validation of the target and establish that bacterial topoisomerase I is druggable. Bacterial topoisomerase I is a potentially high value target for discovery of new antibiotics. Demonstration of topoisomerase I as the cellular target of an antibacterial compound would provide proof-of-concept validation.

  8. Inflation targeting challenges in emerging market countries: The case of Serbia

    Directory of Open Access Journals (Sweden)

    Šoškić Dejan

    2015-01-01

    Full Text Available In the past two decades Inflation targeting has been the monetary policy framework of choice for many developed nations around the world. A significant number of emerging market countries have gradually subscribed to the same monetary regime, but with different levels of success. Certain differences among emerging markets in terms of overall macroeconomic environment, strength of basic monetary policy tools, and institutional development have had an effect on the performance of inflation targeting. This paper focuses on the fulfilment of basic preconditions for implementation of inflation targeting in emerging market countries, and on results and challenges of inflation targeting implementation in Serbia more than six years after its introduction. Special attention is paid to high dollarization (euroization, which poses a serious challenge for inflation targeting, and to modification of the Taylor rule for dollarized economies. For inflation targeting in Serbia to be more effective, a (gradual decrease in overall dollarization (euroization, fiscal discipline and sustainability, and an increase in the independence and capacity of the central bank are needed, among other things. [Projekat Ministarstva nauke Republike Srbije, br. 179005: Risks of Financial Institutions and Markets in Serbia -Microeconomic and Macroeconomic Approaches

  9. 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

    ethical challenges that take into consideration the perspectives of employees, targeted organisations, online outlet administrators and audiences. The ethical challenge for employees is to disclose problems for organisational and societal changes in a safe context and supported by a large audience, while......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...... 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...

  10. The VG/GA strain of Newcastle disease virus: Mucosal immunity, protection against lethal challenge and molecular analysis

    Science.gov (United States)

    The VG/GA strain of Newcastle disease virus (NDV) isolated from the intestine of healthy turkeys has been proposed to replicate in the respiratory and intestinal tract of chickens. In this study, the virus distribution, the mucosal and systemic immune response, the efficacy against lethal challenge...

  11. 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...

  12. A strategy for constructing aneuploid yeast strains by transient nondisjunction of a target chromosome

    Directory of Open Access Journals (Sweden)

    Peck Anders T

    2009-07-01

    Full Text Available Abstract Background Most methods for constructing aneuploid yeast strains that have gained a specific chromosome rely on spontaneous failures of cell division fidelity. In Saccharomyces cerevisiae, extra chromosomes can be obtained when errors in meiosis or mitosis lead to nondisjunction, or when nuclear breakdown occurs in heterokaryons. We describe a strategy for constructing N+1 disomes that does not require such spontaneous failures. The method combines two well-characterized genetic tools: a conditional centromere that transiently blocks disjunction of one specific chromosome, and a duplication marker assay that identifies disomes among daughter cells. To test the strategy, we targeted chromosomes III, IV, and VI for duplication. Results The centromere of each chromosome was replaced by a centromere that can be blocked by growth in galactose, and ura3::HIS3, a duplication marker. Transient exposure to galactose induced the appearance of colonies carrying duplicated markers for chromosomes III or IV, but not VI. Microarray-based comparative genomic hybridization (CGH confirmed that disomic strains carrying extra chromosome III or IV were generated. Chromosome VI contains several genes that are known to be deleterious when overexpressed, including the beta-tubulin gene TUB2. To test whether a tubulin stoichiometry imbalance is necessary for the apparent lethality caused by an extra chromosome VI, we supplied the parent strain with extra copies of the alpha-tubulin gene TUB1, then induced nondisjunction. Galactose-dependent chromosome VI disomes were produced, as revealed by CGH. Some chromosome VI disomes also carried extra, unselected copies of additional chromosomes. Conclusion This method causes efficient nondisjunction of a targeted chromosome and allows resulting disomic cells to be identified and maintained. We used the method to test the role of tubulin imbalance in the apparent lethality of disomic chromosome VI. Our results indicate

  13. Therapeutic targeting of microRNAs: current status and future challenges.

    Science.gov (United States)

    Li, Zhonghan; Rana, Tariq M

    2014-08-01

    MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that have crucial roles in regulating gene expression. Increasing evidence supports a role for miRNAs in many human diseases, including cancer and autoimmune disorders. The function of miRNAs can be efficiently and specifically inhibited by chemically modified antisense oligonucleotides, supporting their potential as targets for the development of novel therapies for several diseases. In this Review we summarize our current knowledge of the design and performance of chemically modified miRNA-targeting antisense oligonucleotides, discuss various in vivo delivery strategies and analyse ongoing challenges to ensure the specificity and efficacy of therapeutic oligonucleotides in vivo. Finally, we review current progress on the clinical development of miRNA-targeting therapeutics.

  14. 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.

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

    Science.gov (United States)

    Jiang, Feng; Liu, Biao; Lu, Jun; Li, Fangfei; Li, Defang; Liang, Chao; Dang, Lei; Liu, Jin; He, Bing; Badshah, Shaikh Atik; Lu, Cheng; He, Xiaojuan; Guo, Baosheng; Zhang, Xiao-Bing; Tan, Weihong; Lu, Aiping; Zhang, Ge

    2015-01-01

    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.

  16. Algal bioremediation of waste waters from land-based aquaculture using ulva: selecting target species and strains.

    Science.gov (United States)

    Lawton, Rebecca J; Mata, Leonardo; de Nys, Rocky; Paul, Nicholas A

    2013-01-01

    The optimised reduction of dissolved nutrient loads in aquaculture effluents through bioremediation requires selection of appropriate algal species and strains. The objective of the current study was to identify target species and strains from the macroalgal genus Ulva for bioremediation of land-based aquaculture facilities in Eastern Australia. We surveyed land-based aquaculture facilities and natural coastal environments across three geographic locations in Eastern Australia to determine which species of Ulva occur naturally in this region and conducted growth trials at three temperature treatments on a subset of samples from each location to determine whether local strains had superior performance under local environmental conditions. DNA barcoding using the markers ITS and tufA identified six species of Ulva, with U. ohnoi being the most common blade species and U. sp. 3 the most common filamentous species. Both species occurred at multiple land-based aquaculture facilities in Townsville and Brisbane and multiple strains of each species grew well in culture. Specific growth rates of U. ohnoi and U. sp. 3 were high (over 9% and 15% day(-1) respectively) across temperature treatments. Within species, strains of U. ohnoi had higher growth in temperatures corresponding to local conditions, suggesting that strains may be locally adapted. However, across all temperature treatments Townsville strains had the highest growth rates (11.2-20.4% day(-1)) and Sydney strains had the lowest growth rates (2.5-8.3% day(-1)). We also found significant differences in growth between strains of U. ohnoi collected from the same geographic location, highlighting the potential to isolate and cultivate fast growing strains. In contrast, there was no clearly identifiable competitive strain of filamentous Ulva, with multiple species and strains having variable performance. The fast growth rates and broad geographical distribution of U. ohnoi make this an ideal species to target for

  17. 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

    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...... interangle reproducibility on the basis of one standard and one alternative image acquisition relative to intraobserver reproducibility of two standard views of the same left ventricular segments. A single-window comparison was used to evaluated septal LPS: standard apical four-chamber versus right...... and alternative window comparisons was lower than the interangle difference in global LPS (-1.0 ± 0.1% vs -2.1 ± 2.4%). Intraobserver reproducibility was significantly higher than interangle reproducibility (intraclass correlation coefficient = 0.9 vs 0.29, P segmental...

  18. Promise and challenges on the horizon of MET-targeted cancer therapeutics

    Institute of Scientific and Technical Information of China (English)

    Yu-Wen; Zhang

    2015-01-01

    MET(MNNG HOS transforming gene) is one of the receptor tyrosine kinases whose activities are frequently altered in human cancers, and it is a promising therapeutic target. MET is normally activated by its lone ligand, hepatocyte growth factor(HGF), eliciting its diverse biological activities that are crucial for development and physiology. Alteration of the HGF-MET axis results in inappropriate activation of a cascade of intracellular signaling pathways that contributes to hallmark cancer events including deregulated cell proliferation and survival, angiogenesis, invasion, andmetastasis. Aberrant MET activation results from autocrine or paracrine mechanisms due to overexpression of HGF and/or MET or from a ligand-independent mechanism caused by activating mutations or amplification of MET. The literature provides compelling evidence for the role of MET signaling in cancer development and progression. The finding that cancer cells often use MET activation to escape therapies targeting other pathways strengthens the argument for MET-targeted therapeutics. Diverse strategies have been explored to deactivate MET signaling, and compounds and biologics targeting the MET pathway are in clinical development. Despite promising results from various clinical trials, we are still waiting for true MET-targeted therapeutics in the clinic. This review will explore recent progress and hurdles in the pursuit of METtargeted cancer drugs and discuss the challenges in such development.

  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. 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...

  1. Combining targeted therapy with immunotherapy in BRAF-mutant melanoma: promise and challenges.

    Science.gov (United States)

    Hu-Lieskovan, Siwen; Robert, Lidia; Homet Moreno, Blanca; Ribas, Antoni

    2014-07-20

    Recent breakthroughs in the treatment of advanced melanoma are based on scientific advances in understanding oncogenic signaling and the immunobiology of this cancer. Targeted therapy can successfully block oncogenic signaling in BRAF(V600)-mutant melanoma with high initial clinical responses, but relapse rates are also high. Activation of an immune response by releasing inhibitory check points can induce durable responses in a subset of patients with melanoma. These advances have driven interest in combining both modes of therapy with the goal of achieving high response rates with prolonged duration. Combining BRAF inhibitors and immunotherapy can specifically target the BRAF(V600) driver mutation in the tumor cells and potentially sensitize the immune system to target tumors. However, it is becoming evident that the effects of paradoxical mitogen-activated protein kinase pathway activation by BRAF inhibitors in non-BRAF-mutant cells needs to be taken into account, which may be implicated in the problems encountered in the first clinical trial testing a combination of the BRAF inhibitor vemurafenib with ipilimumab (anti-CTLA4), with significant liver toxicities. Here, we present the concept and potential mechanisms of combinatorial activity of targeted therapy and immunotherapy, review the literature for evidence to support the combination, and discuss the potential challenges and future directions for rational conduct of clinical trials.

  2. Resistance to cancer treatment: the role of somatic genetic events and the challenges for targeted therapies

    Directory of Open Access Journals (Sweden)

    Gerald eBatist

    2011-10-01

    Full Text Available Therapeutic resistance remains a major cause of cancer-related deaths. Resistance can occur from the outset of treatment or as an acquired phenomenon after an initial clinical response. Therapeutic resistance is an almost universal phenomenon in the treatment of metastatic cancers. The advent of molecularly targeted treatments brought greater efficacy in patients whose tumors express a particular target or molecular signature. However, resistance remains a predictable challenge. This article provides an overview of somatic genomic events that confer resistance to cancer therapies. Some examples, including BCR-ABL, EML4-ALK, and the androgen receptor, contain mutations in the target itself, which hamper binding and inhibitory functions of therapeutic agents. There are also examples of somatic genetic changes in other genes or pathways that result in resistance by circumventing the inhibitor, as in resistance to trastuzumab and BRAF inhibitors. Yet other examples results in activation of cytoprotective genes. The fact that all of these mechanisms of resistance are due to somatic changes in the tumor’s genome makes targeting them selectively a feasible goal. To identify and validate these changes, it is important to obtain biopsies o

  3. Administration of a Salmonella Enteritidis ΔhilAssrAfliG strain by coarse spray to newly hatched broilers reduces colonization and shedding of a Salmonella Enteritidis challenge strain.

    Science.gov (United States)

    De Cort, W; Haesebrouck, F; Ducatelle, R; van Immerseel, F

    2015-01-01

    Consumption of contaminated poultry meat is still an important cause of Salmonella infections in humans. Colonization inhibition (CI) occurs when a live Salmonella strain is administered to chickens and subsequently protects against challenge with another Salmonella strain belonging to the same serotype. A Salmonella Enteritidis hilAssrAfliG deletion mutant has previously been proven to reduce colonization and shedding of a wild-type Salmonella Enteritidis strain in newly hatched broilers after experimental infection. In this study, we compared two administration routes for this strain. Administering the Salmonella Enteritidis ΔhilAssrAfliG strain through drinking water on the first day of life resulted in decreased fecal shedding and cecal colonization of a wild-type Salmonella Enteritidis challenge strain administered 24 h later using a seeder-bird model. When administering the CI strain by coarse spray on newly hatched broiler chicks, an even more pronounced reduction of cecal colonization was observed, and fecal shedding of the Salmonella Enteritidis challenge strain ceased during the course of the experiment. These data suggest that administering a Salmonella Enteritidis ΔhilAssrAfliG strain to newly hatched chicks using a coarse spray is a useful and effective method that reduces colonization and shedding of a wild-type Salmonella Enteritidis strain after early challenge.

  4. Interindividual Variation in the Relationship of Different Intensity Markers—A Challenge for Targeted Training Prescriptions

    Science.gov (United States)

    Meyer, Tim; Hecksteden, Anne

    2016-01-01

    Purpose Training intensities are frequently prescribed as relative workloads based on a single reference value (e.g. maximum oxygen uptake). However, exercise-induced physical strain is multifaceted and large interindividual variability in intensity markers has been reported for constant load exercise with standardized relative intensity. This questions the accuracy of (univariate) relative intensities in targeting specific training stimuli. The present trial aims to investigate interindividual variability in the relationship of strain indicators using interpolated performance curves derived from constant load tests at different workloads. This approach enables the prediction of other indicators based on a chosen reference and subsequent comparison of predictive accuracy between group-based and individualized regression models. Methods 15 competitive cyclists completed a stepwise incremental cycling test followed by 5 constant load tests with the same absolute workloads as in the stepwise incremental test. The highest of theses workloads which yielded a lactate (BLa) steady state was repeated enabling estimation of intraindividual variability. From constant load tests, the courses of BLa relative to the respective reference value (e.g. %VO2peak) were interpolated by polynomial regression. Variability between individual regression curves was analyzed by mixed modeling. Predictive accuracy was estimated as the sum of squared differences between predicted and observed values. Results The proportion of total variation in the course of BLa relative to the respective reference parameter accounted for by subject identity ranged between 36 and 51%. A significant increase in predictive accuracy was observed for VO2peak and HRmax, respectively, as predicting parameters. Conclusion These results are in support of a multivariable, individualized approach to intensity prescriptions when aiming at accurately targeted perturbations of homeostasis. PMID:27788182

  5. 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.

  6. School-Based Interventions Targeting Challenging Behaviors Exhibited by Young Children with Autism Spectrum Disorder: A Systematic Literature Review

    Science.gov (United States)

    Martinez, Jose R.; Werch, Brittany L.; Conroy, Maureen A.

    2016-01-01

    The purpose of this review was to critically examine and summarize the impact of school-based interventions designed to decrease challenging behaviors in young children with Autism Spectrum Disorder (ASD). Reviewed studies employed a single-case experimental design, targeted challenging behaviors, included children 3-8 years old with ASD, and took…

  7. Metabolomics as a tool for target identification in strain improvement: the influence of phenotype definition.

    Science.gov (United States)

    Braaksma, Machtelt; Bijlsma, Sabina; Coulier, Leon; Punt, Peter J; van der Werf, Mariët J

    2011-01-01

    For the optimization of microbial production processes, the choice of the quantitative phenotype to be optimized is crucial. For instance, for the optimization of product formation, either product concentration or productivity can be pursued, potentially resulting in different targets for strain improvement. The choice of a quantitative phenotype is highly relevant for classical improvement approaches, and even more so for modern systems biology approaches. In this study, the information content of a metabolomics dataset was determined with respect to different quantitative phenotypes related to the formation of specific products. To this end, the production of two industrially relevant products by Aspergillus niger was evaluated: (i) the enzyme glucoamylase, and (ii) the more complex product group of secreted proteases, consisting of multiple enzymes. For both products, six quantitative phenotypes associated with activity and productivity were defined, also taking into account different time points of sampling during the fermentation. Both linear and nonlinear relationships between the metabolome data and the different quantitative phenotypes were considered. The multivariate data analysis tool partial least-squares (PLS) was used to evaluate the information content of the datasets for all the different quantitative phenotypes defined. Depending on the product studied, different quantitative phenotypes were found to have the highest information content in specific metabolomics datasets. A detailed analysis of the metabolites that showed strong correlation with these quantitative phenotypes revealed that various sugar derivatives correlated with glucoamylase activity. For the reduction of protease activity, mainly as-yet-unidentified compounds correlated.

  8. Challenges in the design of clinically useful brain-targeted drug nanocarriers.

    Science.gov (United States)

    Costantino, L; Boraschi, D; Eaton, M

    2014-01-01

    Nowadays, the delivery of drugs by means of intravenously administered nanosized drug carriers - polymerdrug conjugates, liposomes and micelles, is technically possible. These delivery systems are mainly designed for tumour therapy, and accumulate passively into tumours by means of the well known EPR effect. Targeted nanocarriers, that additionally contain ligands for receptors expressed on cell surfaces, are also widely studied but products of this kind are not marketed, and only a few are in clinical trial. Polymeric nanoparticles (Np) able to deliver drugs to the CNS were pioneered in 1995; a number of papers have been published dealing with brain-targeted drug delivery using polymeric Np able to cross the BBB, mainly for the treatment of brain tumours. At present, however, the translation potential of these Np seems to have been exceeded by targeted liposomes, a platform based on a proven technology. This drug delivery system entered clinical trials soon after its discovery, while the challenges in formulation, characterization and manufacturing of brain-targeted polymeric Np and the cost/benefit ratio could be the factors that have prevented their development. A key issue is that it is virtually impossible to define the in vivo fate of polymers, especially in the brain, which is a regulatory requirement; perhaps this is why no progress has been made. The most advanced Np for brain tumours treatment will be compared here with the published data available for those in clinical trial for tumours outside the CNS, to highlight the knowledge gaps that still penalise these delivery systems. At present, new approaches for brain tumours are emerging, such as lipid Np or the use of monoclonal antibody (mAb)-drug conjugates, which avoid polymers. The success or failure in the approval of the polymeric Np currently in clinical trials will certainly affect the field. At present, the chances of their approval appear to be very low.

  9. Evidence for strain-specific differences in benzene toxicity as a function of host target cell susceptibility.

    Science.gov (United States)

    Neun, D J; Penn, A; Snyder, C A

    1992-01-01

    It has long been recognized that benzene exposure produces disparate toxic responses among different species or even among different strains within the same species. There is ample evidence that species- or strain-dependent differences in metabolic activity correlate with the disparate responses to benzene. However, bone marrow cells (the putative targets of benzene toxicity) may also exhibit species- or strain-dependent differences in susceptibility to the toxic effects of benzene. To investigate this hypothesis, two sets of companion experiments were performed. First, two strains of mice, Swiss Webster (SW) and C57B1/6J (C57), were exposed to 300 ppm benzene via inhalation and the effects of the exposures were determined on bone marrow cellularity and the development of bone marrow CFU-e (Colony Forming Unit-erythroid, an early red cell progenitor). Second, bone marrow cells from the same strains were exposed in vitro to five known benzene metabolites (1,4 benzoquinone, catechol, hydroquinone, muconic acid, and phenol) individually and in binary combinations. Benzene exposure, in vivo, reduced bone marrow cellularity and the development of CFU-e in both strains; however, reductions in both these endpoints were more severe in the SW strain. When bone marrow cells from the two strains were exposed in vitro to the five benzene metabolites individually, benzoquinone, hydroquinone, and catechol reduced the numbers of CFU-e in both strains in dose-dependent responses, phenol weakly reduced the numbers of the C57 CFU-e only and in a non-dose-dependent manner, and muconic acid was without effect on cells from either strain.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Targeted immunotherapy of cancer with CAR T cells: achievements and challenges.

    Science.gov (United States)

    Lipowska-Bhalla, Grazyna; Gilham, David E; Hawkins, Robert E; Rothwell, Dominic G

    2012-07-01

    The adoptive transfer of chimeric antigen receptor (CAR)-expressing T cells is a relatively new but promising approach in the field of cancer immunotherapy. This therapeutic strategy is based on the genetic reprogramming of T cells with an artificial immune receptor that redirects them against targets on malignant cells and enables their destruction by exerting T cell effector functions. There has been an explosion of interest in the use of CAR T cells as an immunotherapy for cancer. In the pre-clinical setting, there has been a considerable focus upon optimizing the structural and signaling potency of the CAR while advances in bio-processing technology now mean that the clinical testing of these gene-modified T cells has become a reality. This review will summarize the concept of CAR-based immunotherapy and recent clinical trial activity and will further discuss some of the likely future challenges facing CAR-modified T cell therapies.

  11. Comparative Analysis of Two Gene-Targeting Approaches Challenges the Tumor-Suppressive Role of the Protein Kinase MK5/PRAK.

    Directory of Open Access Journals (Sweden)

    Natalia Ronkina

    Full Text Available MK5 (MAPK-activated protein kinase 5 or PRAK (p38-regulated and -activated kinase are alternative names for a serine/threonine protein kinase downstream to ERK3/4 and p38 MAPK. A previous gene targeting approach for MK5/PRAK (termed here MK5/PRAK-Δex8 revealed a seemingly tumor-suppressive role of MK5/PRAK in DMBA-induced one step skin carcinogenesis and Ras-induced transformation. Here we demonstrate that an alternative targeting strategy of MK5/PRAK (termed MK5/PRAK-Δex6 increased neither tumor incidence in the one step skin carcinogenesis model, nor Ras-induced transformation in primary cells. Interestingly, due to the targeting strategies and exon skipping both knockouts do not completely abolish the generation of MK5/PRAK protein, but express MK5/PRAK deletion mutants with different biochemical properties depending on the exon targeted: Targeting of exon 6 leads to expression of an unstable cytoplasmic catalytically inactive MK5/PRAK-Δex6 mutant while targeting of exon 8 results in a more stable nuclear MK5/PRAK-Δex8 mutant with residual catalytic activity. The different properties of the MK5/PRAK deletion mutants could be responsible for the observed discrepancy between the knockout strains and challenge the role of MK5/PRAK in p53-dependent tumor suppression. Further MK5/PRAK knockout and knock-in mouse strains will be necessary to assign a physiological function to MK5/PRAK in this model organism.

  12. Challenges of clinical trial design for targeted agents against pediatric leukemias

    Directory of Open Access Journals (Sweden)

    Francis Jay Mussai

    2015-01-01

    Full Text Available The past 40 years have seen significant improvements in both event-free and overall survival for children with acute lymphoblastic or acute myeloid leukemia (ALL or AML respectively. Serial national and international clinical trials have optimised the use of conventional chemotherapeutic drugs and, along with improvements in supportive care that have enabled the delivery of more intensive regimens, have been responsible for the major improvements in patient outcome seen over the past few decades,. The benefits of dose intensification, however, have likely now been maximised, and over the same period, the identification of new cytotoxic drugs has been limited.As the biology of leukemogenesis has become better understood, key molecules and intracellular pathways have been identified that offer the possibility of targeting directly the leukemia cells whilst sparing normal cells. Consequently, there is now a drive to develop novel leukemia-specific or ‘targeted’ therapies. These new classes of drugs will have mechanisms of action, toxicities and therapeutic indices quite different from conventional cytotoxic drugs previously encountered, thus rendering current clinical trial methodologies inappropriate; clinical trial methods will need to be adapted to accommodate these features of these new classes of drugs. This review will address the challenges and some of the techniques for developing clinical trials for targeted therapies.

  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. Gibberellins in Penicillium strains: Challenges for endophyte-plant host interactions under salinity stress.

    Science.gov (United States)

    Leitão, Ana Lúcia; Enguita, Francisco J

    2016-02-01

    The genus Penicillium is one of the most versatile "mycofactories", comprising some species able to produce gibberellins, bioactive compounds that can modulate plant growth and development. Although plants have the ability to synthesize gibberellins, their levels are lower when plants are under salinity stress. It has been recognized that detrimental abiotic conditions, such as saline stress, have negative effects on plants, being the availability of bioactive gibberellins a critical factor for their growth under this conditions. This review summarizes the interplay existing between endophytic Penicillium strains and plant host interactions, with focus on bioactive gibberellins production as a fungal response that allows plants to overcome salinity stress.

  15. 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 < 0.05). Bovine colostrum, an additive containing thyme extract and an organic acid 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.

  16. Telomerase as an emerging target to fight cancer--opportunities and challenges for nanomedicine.

    Science.gov (United States)

    Philippi, C; Loretz, B; Schaefer, U F; Lehr, C M

    2010-09-01

    Telomerase as an enzyme is responsible for the renewal of the chromosomal ends, the so-called telomeres. By preventing them from shortening with each cell cycle, telomerase is able to inhibit cellular senescence and apoptosis. Telomerase activity, which is detectable in the majority of cancer cells, allows them to maintain their proliferative capacity. The thus obtained immortality of those cells again is a key to their malignancy. Based on these discoveries, it is obvious that telomerase inhibitors would represent an innovative approach to fight cancer, and a variety of such candidate molecules are currently in the pipeline. Telomerase inhibitors largely fall in two classes of compounds: small synthetic molecules and nucleotide-based biologicals. For several candidates, some proof of concept studies have been demonstrated, either on cell cultures or in animal models. But the same studies also revealed that inefficient delivery is largely limiting the translational step into the clinic. The most appealing feature of telomerase inhibitors, which distinguishes them from conventional anticancer drugs, is probably seen in their intrinsic non-toxicity to normal cells. Nevertheless, efficient delivery to the target cells, i.e. to the tumor, is still required. Here, some well-known biopharmaceutical problems such as insufficient solubility, permeability or even metabolic stability are frequently encountered. To address these challenges, there is a clear need for adequate delivery technologies, for example by using nanomedicines, that would allow to overcome their biopharmaceutical shortcomings and to warrant a sufficient bioavailability at the target side. This review first briefly explains the concept of telomerase and telomerase inhibition in cancer therapy. It secondly aims to provide an overview of the different currently known telomerase inhibitors. Finally, the biopharmaceutical limitations of these molecules are discussed as well as the possibilities to overcome

  17. Multi-Strain Deterministic Chaos in Dengue Epidemiology, A Challenge for Computational Mathematics

    Science.gov (United States)

    Aguiar, Maíra; Kooi, Bob W.; Stollenwerk, Nico

    2009-09-01

    Recently, we have analysed epidemiological models of competing strains of pathogens and hence differences in transmission for first versus secondary infection due to interaction of the strains with previously aquired immunities, as has been described for dengue fever, known as antibody dependent enhancement (ADE). These models show a rich variety of dynamics through bifurcations up to deterministic chaos. Including temporary cross-immunity even enlarges the parameter range of such chaotic attractors, and also gives rise to various coexisting attractors, which are difficult to identify by standard numerical bifurcation programs using continuation methods. A combination of techniques, including classical bifurcation plots and Lyapunov exponent spectra has to be applied in comparison to get further insight into such dynamical structures. Especially, Lyapunov spectra, which quantify the predictability horizon in the epidemiological system, are computationally very demanding. We show ways to speed up computations of such Lyapunov spectra by a factor of more than ten by parallelizing previously used sequential C programs. Such fast computations of Lyapunov spectra will be especially of use in future investigations of seasonally forced versions of the present models, as they are needed for data analysis.

  18. 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...

  19. Identification of replication-competent HSV-1 Cgal+ strain targets in a mouse model of human hepatocarcinoma xenograft

    OpenAIRE

    Santamaria, E. (Enrique); Mora, M.I.; Carro-Roldan, E. (Elvira); M Molina; Fernandez-Irigoyen, J. (Joaquín); Marconi, P; Manservigi, R; Greco, A.; Epstein, A L; Prieto, J.; Hernandez-Alcoceba, R. (Rubén); Corrales, F. J.

    2009-01-01

    Recent studies based on animal models have shown the advantages and potential of oncolytic viral therapy using HSV-1 -based replication-competent vectors in the treatment of liver tumors, but little is known about the cellular targets that are modulated during viral infection. In the present work, we have studied the effects of intratumoral injections of HSV-1 Cgal(+) strain in a murine model of human hepatoma xenografts. Viral replication was assessed for more than 1month, leading to a signi...

  20. Computational Challenges in miRNA Target Predictions: To Be or Not to Be a True Target?

    Directory of Open Access Journals (Sweden)

    Christian Barbato

    2009-01-01

    Full Text Available All microRNA (miRNA target—finder algorithms return lists of candidate target genes. How valid is that output in a biological setting? Transcriptome analysis has proven to be a useful approach to determine mRNA targets. Time course mRNA microarray experiments may reliably identify downregulated genes in response to overexpression of specific miRNA. The approach may miss some miRNA targets that are principally downregulated at the protein level. However, the high-throughput capacity of the assay makes it an effective tool to rapidly identify a large number of promising miRNA targets. Finally, loss and gain of function miRNA genetics have the clear potential of being critical in evaluating the biological relevance of thousands of target genes predicted by bioinformatic studies and to test the degree to which miRNA-mediated regulation of any “validated” target functionally matters to the animal or plant.

  1. Challenges and strategies for targeted phosphorylation site identification and quantification using mass spectrometry analysis.

    Science.gov (United States)

    Blackburn, Kevin; Goshe, Michael B

    2009-03-01

    Despite its importance, the 'ultimate' method to identify and quantify site-specific protein phosphorylation using mass spectrometry (MS) has yet to be established. This is as much a function of the dynamic range of instrumentation as it is the complexities surrounding the isolation and behavior of phosphopeptides. Phosphorylation site analysis using MS can be quite challenging when analyzing just one protein and quickly becomes a daunting task when attempting to perform proteome-wide measurements. Data-dependent tandem MS-based methods which are useful for the discovery and characterization of novel phosphorylation sites often lack the dynamic range and quantitative aspect required for studying the temporal phases of phosphorylation. While targeted methods such as multiple reaction monitoring do provide a highly specific and quantitative methodology for studying phosphorylation changes over time, they are not suited for initial discovery of previously unreported sites of phosphorylation. Data-independent acquisition represents a relatively new approach for simultaneous qualitative and quantitative sample analysis which holds promise for filling this technological gap.

  2. Setting quality and safety priorities in a target-rich environment: an academic medical center's challenge.

    Science.gov (United States)

    Mort, Elizabeth A; Demehin, Akinluwa A; Marple, Keith B; McCullough, Kathryn Y; Meyer, Gregg S

    2013-08-01

    Hospitals are continually challenged to provide safer and higher-quality patient care despite resource constraints. With an ever-increasing range of quality and safety targets at the national, state, and local levels, prioritization is crucial in effective institutional quality goal setting and resource allocation.Organizational goal-setting theory is a performance improvement methodology with strong results across many industries. The authors describe a structured goal-setting process they have established at Massachusetts General Hospital for setting annual institutional quality and safety goals. Begun in 2008, this process has been conducted on an annual basis. Quality and safety data are gathered from many sources, both internal and external to the hospital. These data are collated and classified, and multiple approaches are used to identify the most pressing quality issues facing the institution. The conclusions are subject to stringent internal review, and then the top quality goals of the institution are chosen. Specific tactical initiatives and executive owners are assigned to each goal, and metrics are selected to track performance. A reporting tool based on these tactics and metrics is used to deliver progress updates to senior hospital leadership.The hospital has experienced excellent results and strong organizational buy-in using this effective, low-cost, and replicable goal-setting process. It has led to improvements in structural, process, and outcomes aspects of quality.

  3. Application of Deletion- Targeted Multiplex PCR technique for detection of Mycobacterium tuberculosis Beijing strains in samples from tuberculosis patients.

    Directory of Open Access Journals (Sweden)

    Azar Dokht Khosravi

    2014-10-01

    Full Text Available Molecular epidemiological studies have shown that certain genotypes of Mycobacterium tuberculosis (MTB are over-represented in limited geographical regions, suggesting of evolution of certain genotypes with increasing virulence and pathogenicity. Beijing strain of MTB was initially described by its potential to cause outbreaks worldwide and its association with drug resistance. Due to tuberculosis (TB-related mortality which is associated with Beijing genotype, this study was designed with the aim to detect the MTB Beijing genotype in the region of study.A total of 170 clinical isolates of MTB were collected from the TB reference laboratory of Khuzestan province, Iran, over one year period from February 2010 to February 2011. Phenotypic tests were used for preliminary detection of MTB. Culture positive MTB isolates were confirmed by multiplex PCR based on IS6110 gene with subsequent screening for resistance to isoniazid (INH, and rifampin (RIF by PCR using relevant primers. Three set of primers were used to differentiate Beijing from non-Beijing strains by using Deletion- Targeted Multiplex (DTM PCR.From 160 PCR-confirmed MTB isolates, 18 (11.25% showed mutation in katG gene related to INH resistance and 20 (12.5%, associated with mutation in rpoB gene related to RIF resistance, and 8 (5% were detected as Beijing strain using multiplex PCR. The majority of detected Beijing strains (6/8[75%] comprised mutation in katG gene with the prevalent mutation specifically in codon 315. In 4 Beijing strains (2.5%, mutation in rpoB gene were also detected.Using DTM- PCR, the rate of Beijing strains in the region of study was determined as 5%. Although for detection of MTB antimicrobial resistance, it is advised to use a combination of conventional antimicrobial susceptibility testing and molecular techniques, however for time saving, it seems that DTM-PCR, is a simple technique for use in areas of the world where Beijing strains are highly prevalent.

  4. 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 (Pabortus strains 544 and 2308, can be used in immunogenicity tests of S19 and RB51 vaccines.

  5. 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.

  6. Engineering of Escherichia coli strains for plasmid biopharmaceutical production: scale-up challenges.

    Science.gov (United States)

    Gonçalves, Geisa A L; Prather, Kristala L J; Monteiro, Gabriel A; Prazeres, Duarte M F

    2014-05-19

    Plasmid-based vaccines and therapeutics have been making their way into the clinic in the last years. The existence of cost-effective manufacturing processes capable of delivering high amounts of high-quality plasmid DNA (pDNA) is essential to generate enough material for trials and support future commercialization. However, the development of pDNA manufacturing processes is often hampered by difficulties in predicting process scale performance of Escherichia coli cultivation on the basis of results obtained at lab scale. This paper reports on the differences observed in pDNA production when using shake flask and bench-scale bioreactor cultivation of E. coli strains MG1655ΔendAΔrecA and DH5α in complex media with 20 g/L of glucose. MG1655ΔendAΔrecA produced 5-fold more pDNA (9.8 mg/g DCW) in bioreactor than in shake flask (1.9 mg/g DCW) and DH5α produced 4-fold more pDNA (8 mg/g DCW) in bioreactor than in shake flask (2 mg/g DCW). Accumulation of acetate was also significant in shake flasks but not in bioreactors, a fact that was attributed to a lack of control of pH.

  7. 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.

  8. Dendritic Cell Targeting of Bacillus anthracis Protective Antigen Expressed by Lactobacillus acidophilus Protects Mice from Lethal Challenge

    Science.gov (United States)

    2008-10-28

    Dendritic cell targeting of Bacillus anthracis protective antigen expressed by Lactobacillus acidophilus protects mice from lethal challenge M...lethal chal- lenge. A vaccine strategy was established by using Lactobacillus acidophilus to deliver Bacillus anthracis protective antigen (PA) via...include species of Lactobacillus , Lactococcus, Leuconostoc, Pedio- coccus, and Streptococcus. It is widely accepted that Lactobacillus species play a

  9. Central nervous system myeloid cells as drug targets: current status and translational challenges.

    Science.gov (United States)

    Biber, Knut; Möller, Thomas; Boddeke, Erik; Prinz, Marco

    2016-02-01

    Myeloid cells of the central nervous system (CNS), which include parenchymal microglia, macrophages at CNS interfaces and monocytes recruited from the circulation during disease, are increasingly being recognized as targets for therapeutic intervention in neurological and psychiatric diseases. The origin of these cells in the immune system distinguishes them from ectodermal neurons and other glia and endows them with potential drug targets distinct from classical CNS target groups. However, despite the identification of several promising therapeutic approaches and molecular targets, no agents directly targeting these cells are currently available. Here, we assess strategies for targeting CNS myeloid cells and address key issues associated with their translation into the clinic.

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

    Science.gov (United States)

    Pan, Y; Chatterjee, D; Gerlai, R

    2012-12-05

    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, we further characterize these strains using semi-quantitative RT-PCR to measure the expression of ten selected genes and HPLC to measure the levels of nine neurochemicals. We chose the target genes and neurochemicals based upon their potential involvement in alcohol and other drugs of abuse related mechanisms. We quantified the expression of the genes encoding D1-R, D2a-R, D4a-R dopamine receptors, GABA(A)-R, GABA(B)-R1, GAD1, MAO, NMDA-R (NR2D subunit), 5HT-R1bd and SLC6 a4a. We found the gene encoding D1 dopamine receptor over-expressed and the genes encoding GABA(B1) receptor and solute family carrier protein 6 (SLC6) 4a under-expressed in SF compared to AB. We also found the level of all (dopamine, DOPAC, Serotonin, GABA, Glutamate, Glycine, Aspartate, Taurine) but one (5HIAA) neurochemicals tested decreased in SF as compared to AB. These results, combined with previously identified behavioral differences between the AB and SF strains, demonstrate the importance of strain characterization in zebrafish. They now also allow formulation of working hypotheses about possible mechanisms underlying the differential effects of acute and chronic alcohol treatment on these two zebrafish strains.

  11. One time intranasal vaccination with a modified vaccinia Tiantan strain MVTT(ZCI) protects animals against pathogenic viral challenge.

    Science.gov (United States)

    Yu, Wenbo; Fang, Qing; Zhu, Weijun; Wang, Haibo; Tien, Po; Zhang, Linqi; Chen, Zhiwei

    2010-02-25

    To combat variola virus in bioterrorist attacks, it is desirable to develop a noninvasive vaccine. Based on the vaccinia Tiantan (VTT) strain, which was historically used to eradicate the smallpox in China, we generated a modified VTT (MVTT(ZCI)) by removing the hemagglutinin gene and an 11,944bp genomic region from HindIII fragment C2L to F3L. MVTT(ZCI) was characterized for its host cell range in vitro and preclinical safety and efficacy profiles in mice. Despite replication-competency in some cell lines, unlike VTT, MVTT(ZCI) did not cause death after intracranial injection or body weight loss after intranasal inoculation. MVTT(ZCI) did not replicate in mouse brain and was safe in immunodeficient mice. MVTT(ZCI) induced neutralizing antibodies via the intranasal route of immunization. One time intranasal immunization protected animals from the challenge of the pathogenic vaccinia WR strain. This study established proof-of-concept that the attenuated replicating MVTT(ZCI) may serve as a safe noninvasive smallpox vaccine candidate.

  12. Experimental Challenge of Atlantic Cod (Gadus morhua) with a Brucella pinnipedialis Strain from Hooded Seal (Cystophora cristata)

    Science.gov (United States)

    Nymo, Ingebjørg Helena; Seppola, Marit; Al Dahouk, Sascha; Bakkemo, Kathrine Ryvold; Jiménez de Bagüés, María Pilar; Godfroid, Jacques; Larsen, Anett Kristin

    2016-01-01

    Pathology has not been observed in true seals infected with Brucella pinnipedialis. A lack of intracellular survival and multiplication of B. pinnipedialis in hooded seal (Cystophora cristata) macrophages in vitro indicates a lack of chronic infection in hooded seals. Both epidemiology and bacteriological patterns in the hooded seal point to a transient infection of environmental origin, possibly through the food chain. To analyse the potential role of fish in the transmission of B. pinnipedialis, Atlantic cod (Gadus morhua) were injected intraperitoneally with 7.5 x 107 bacteria of a hooded seal field isolate. Samples of blood, liver, spleen, muscle, heart, head kidney, female gonads and feces were collected on days 1, 7, 14 and 28 post infection to assess the bacterial load, and to determine the expression of immune genes and the specific antibody response. Challenged fish showed an extended period of bacteremia through day 14 and viable bacteria were observed in all organs sampled, except muscle, until day 28. Neither gross lesions nor mortality were recorded. Anti-Brucella antibodies were detected from day 14 onwards and the expression of hepcidin, cathelicidin, interleukin (IL)-1β, IL-10, and interferon (IFN)-γ genes were significantly increased in spleen at day 1 and 28. Primary mononuclear cells isolated from head kidneys of Atlantic cod were exposed to B. pinnipedialis reference (NCTC 12890) and hooded seal (17a-1) strain. Both bacterial strains invaded mononuclear cells and survived intracellularly without any major reduction in bacterial counts for at least 48 hours. Our study shows that the B. pinnipedialis strain isolated from hooded seal survives in Atlantic cod, and suggests that Atlantic cod could play a role in the transmission of B. pinnipedialis to hooded seals in the wild. PMID:27415626

  13. 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.

  14. 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.

  15. From targeting the tumor to targeting the immune system: Transversal challenges in oncology with the inhibition of the PD-1/PD-L1 axis

    Science.gov (United States)

    Bersanelli, Melissa; Buti, Sebastiano

    2017-01-01

    After that the era of chemotherapy in the treatment of solid tumors have been overcome by the “translational era”, with the innovation introduced by targeted therapies, medical oncology is currently looking at the dawn of a new “immunotherapy era” with the advent of immune checkpoint inhibitors (CKI) antibodies. The onset of PD-1/PD-L1 targeted therapy has demonstrated the importance of this axis in the immune escape across almost all human cancers. The new CKI allowed to significantly prolong survival and to generate durable response, demonstrating remarkable efficacy in a wide range of cancer types. The aim of this article is to review the most up to date literature about the clinical effectiveness of CKI antibodies targeting PD-1/PD-L1 axis for the treatment of advanced solid tumors and to explore transversal challenges in the immune checkpoint blockade.

  16. Recombinant herpes simplex virus type 1 strains with targeted mutations relevant for aciclovir susceptibility

    Science.gov (United States)

    Brunnemann, Anne-Kathrin; Liermann, Kristin; Deinhardt-Emmer, Stefanie; Maschkowitz, Gregor; Pohlmann, Anja; Sodeik, Beate; Fickenscher, Helmut; Sauerbrei, Andreas; Krumbholz, Andi

    2016-01-01

    Here, we describe a novel reliable method to assess the significance of individual mutations within the thymidine kinase (TK) gene of herpes simplex virus type 1 (HSV-1) to nucleoside analogue resistance. Eleven defined single nucleotide polymorphisms that occur in the TK gene of clinical HSV-1 isolates and a fluorescence reporter were introduced into the HSV-1 strain 17+ that had been cloned into a bacterial artificial chromosome. The susceptibility of these different strains to aciclovir, penciclovir, brivudin, and foscarnet was determined with a modified cytopathic effect reduction assay. The strains were also tested for their aciclovir susceptibility by measuring the relative fluorescence intensity as an indicator for HSV-1 replication and by quantifying the virus yield. Our data indicate that the amino acid substitutions R41H, R106H, A118V, L139V, K219T, S276R, L298R, S345P, and V348I represent natural polymorphisms of the TK protein, whereas G61A and P84L mediate broad cross-resistance against aciclovir, penciclovir, brivudin, and susceptibility to foscarnet. This method allows the definition of the resistance genotype of otherwise unclear mutations in the TK gene of HSV-1. Thus, it provides a scientific basis for antiviral testing in clinical isolates of patients suffering from serious diseases and will facilitate testing of new antivirals against HSV-1. PMID:27426251

  17. Targeting Head and Neck Cancer Stem Cells: Current Advances and Future Challenges.

    Science.gov (United States)

    Birkeland, A C; Owen, J H; Prince, M E

    2015-11-01

    Cancer stem cells (CSCs), or tumor-initiating cells, comprise a subset of tumor cells with demonstrated ability for tumor growth, invasion, metastasis, and resistance to chemotherapy and radiation. Targeting of CSCs remains an attractive yet elusive therapeutic option, with the goal of increasing specificity and effectiveness in tumor eradication, as well as decreasing off-target or systemic toxicity. Research into further characterization and targeted therapy toward head and neck CSCs is an active and rapidly evolving field. This review discusses the current state of research into therapy against head and neck CSCs and future directions for targeted therapy.

  18. Immunization of African Indigenous Pigs with Attenuated Genotype I African Swine Fever Virus OURT88/3 Induces Protection Against Challenge with Virulent Strains of Genotype I.

    Science.gov (United States)

    Mulumba-Mfumu, L K; Goatley, L C; Saegerman, C; Takamatsu, H-H; Dixon, L K

    2016-10-01

    The attenuated African swine fever virus genotype I strain OURT88/3 has previously been shown to induce protection of European breeds of domestic pigs against challenge with virulent isolates. To determine whether protective immune responses could also be induced in indigenous breeds of pigs from the Kinshassa region in Democratic Republic of Congo, we immunized a group of eight pigs with OURT88/3 strain and challenged the pigs 3 weeks later with virulent genotype I strain OURT88/1. Four of the pigs were protected against challenge. Three of the eight pigs died from African swine fever virus and a fourth from an unknown cause. The remaining four pigs all survived challenge with a recent virulent genotype I strain from the Democratic Republic of Congo, DRC 085/10. Control groups of non-immune pigs challenged with OURT88/1 or DRC 085/10 developed signs of acute ASFV as expected and had high levels of virus genome in blood.

  19. Protection provided by a recombinant ALVAC(®)-WNV vaccine expressing the prM/E genes of a lineage 1 strain of WNV against a virulent challenge with a lineage 2 strain.

    Science.gov (United States)

    Minke, J M; Siger, L; Cupillard, L; Powers, B; Bakonyi, T; Boyum, S; Nowotny, N; Bowen, R

    2011-06-20

    The emergence of lineage 2 strains of WNV in Europe as a cause of clinical disease and mortality in horses raised the question whether the existing WNV vaccines, all based on lineage 1 strains, protect against circulating lineage 2 strains of WNV. In the present paper we have determined the level of cross protection provided by the recombinant ALVAC(®)-WNV vaccine in a severe challenge model that produces clinical signs of WNV type 2 disease. Ten horses were vaccinated twice at 4 weeks interval with one dose of the ALVAC-WNV vaccine formulated at the minimum protective dose. A further 10 horses served as controls. Two weeks after the second vaccination, all horses were challenged intrathecally with a recent neurovirulent lineage 2 strain of WNV. The challenge produced viraemia in 10 out of 10 and encephalitis in 9 out of 10 control horses. Three horses had to be euthanized for humane reasons. In contrast, none of the vaccinated horses developed WNV disease and only 1 vaccinated horse became viraemic at a single time point at low titre. The prevalence of WNV disease and viraemia were significantly lower in the vaccinated horses than in the control horses (Pvaccine will provide veterinarians with an effective tool to control infections caused by lineage 1 and 2 strains of WNV.

  20. 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.

  1. Vpu-Deficient HIV Strains Stimulate Innate Immune Signaling Responses in Target Cells

    OpenAIRE

    Doehle, Brian P.; Chang, Kristina; Fleming, Lamar; McNevin, John; Hladik, Florian; McElrath, M. Juliana; Gale, Michael

    2012-01-01

    Acute virus infection induces a cell-intrinsic innate immune response comprising our first line of immunity to limit virus replication and spread, but viruses have developed strategies to overcome these defenses. HIV-1 is a major public health problem; however, the virus-host interactions that regulate innate immune defenses against HIV-1 are not fully defined. We have recently identified the viral protein Vpu to be a key determinant responsible for HIV-1 targeting and degradation of interfer...

  2. Protection of pigs against challenge with virulent Streptococcus suis serotype 2 strains by a muramidase-released protein and extracellular factor vaccine

    NARCIS (Netherlands)

    Wisselink, H.J.; Vecht, U.; Stockhofe Zurwieden, N.; Smith, H.E.

    2001-01-01

    The efficacy of a muramidase-released protein (MRP) and extracellular factor (EF) vaccine in preventing infection and disease in pigs challenged either with a homologous or a heterologous Streptococcus suis serotype 2 strain (MRP EF ) was compared with the efficacy of a vaccine containing formalin-k

  3. Characterisation of non-toxigenic Clostridium spp. strains, to use as surrogates for non-proteolytic Clostridium botulinum in chilled food challenge testing.

    Science.gov (United States)

    Parker, M D; Barrett, P I; Shepherd, J; Price, L J; Bull, S D

    2015-01-01

    Under many of the conditions studied, a two-strain cocktail of non-toxigenic Clostridium spp. was found to be suitable as a surrogate for non-proteolytic Clostridium botulinum, and has the potential for use in chilled food challenge tests measuring growth. Non-toxigenic surrogates could also be used in thermal process screening studies.

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

    Science.gov (United States)

    Malinowsky, K; Wolff, C; Gündisch, S; Berg, D; Becker, Kf

    2010-12-19

    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 for

  5. 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

  6. Targeting the PI3K/Akt pathway in prostate cancer: challenges and opportunities (review).

    Science.gov (United States)

    Toren, Paul; Zoubeidi, Amina

    2014-11-01

    The PI3K/Akt pathway is an actively pursued therapeutic target in oncology. In prostate cancer, the activation of this pathway appears to be characteristic of many aggressive prostate cancers. Further, activation of the PI3K/Akt pathway is more frequently observed as prostate cancer progresses toward a resistant, metastatic disease. Signalling from this pathway activates numerous survival, growth, metabolic and metastatic functions characteristic of aggressive cancer. Biomarkers of this pathway have correlated activation of this pathway to high grade disease and higher risk of disease progression. Therefore there is significant interest in developing effective strategies to target this pathway in prostate cancer. In this review, we discuss the pre-clinical and clinical data relevant to targeting of the PI3K/Akt pathway in prostate cancer. In particular, we review the rationale and relevance of co-targeting approaches against the PI3K/Akt pathway. It is anticipated that through an improved understanding of the biology of the PI3K/Akt pathway in prostate cancer, relevant biomarkers and rationale combination therapies will optimize targeting of this pathway to improve outcomes among patients with aggressive prostate cancer.

  7. A Salmonella Typhimurium mutant strain capable of RNAi delivery: higher tumor-targeting and lower toxicity.

    Science.gov (United States)

    Cheng, Xiawei; Zhang, Xiaoxin; Zhou, Yuqiang; Zhang, Chunmei; Hua, Zi-Chun

    2014-08-01

    Bacteria are highly versatile and useful tools that could deliver short interfering RNA. In this study, a phoP/phoQ double-deleted Salmonella Typhimurium named VNP(PhoP/Q(-)) based on the genetic background of VNP20009. The biological safety and function of VNP(PhoP/Q(-)) were also analyzed. Our study revealed the following results: (1) VNP(PhoP/Q(-)) exhibited lower titers in tumor-free livers and spleens than VNP20009, (2) The survival of VNP(PhoP/Q(-)) in macrophages and 4T1 tumor cells was significantly reduced compared with that of VNP20009, (3) The tumor-targeting ability of VNP(PhoP/Q(-)) was significantly enhanced compared with that of VNP20009, and the anticancer effects of VNP(pPhoP/Q(-)) and VNP20009 on tumor-bearing mice were similar, (4) VNP(PhoP/Q(-)) could release an shRNA-expressing plasmid and express the EGFP reporter gene in tumor tissue. Therefore, VNP(PhoP/Q(-)) exhibited a better safety level in tumor-free mice and elicited an anti-tumor effect on tumor-bearing mice. Moreover, VNP(PhoP/Q(-)) could release an shRNA-expressing plasmid into the cytoplasm of host cells to silence targeted genes.

  8. 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.

  9. Characterization of Mucosal Immune Responses to Enterotoxigenic Escherichia coli Vaccine Antigens in a Human Challenge Model: Response Profiles after Primary Infection and Homologous Rechallenge with Strain H10407.

    Science.gov (United States)

    Chakraborty, Subhra; Harro, Clayton; DeNearing, Barbara; Ram, Malathi; Feller, Andrea; Cage, Alicia; Bauers, Nicole; Bourgeois, A Louis; Walker, Richard; Sack, David A

    2015-11-18

    Enterotoxigenic Escherichia coli (ETEC) bacteria are the most common bacterial cause of diarrhea in children in resource-poor settings as well as in travelers. Although there are several approaches to develop an effective vaccine for ETEC, no licensed vaccines are currently available. A significant challenge to successful vaccine development is our poor understanding of the immune responses that correlate best with protection against ETEC illness. In this study, ETEC-specific mucosal immune responses were characterized and compared in subjects challenged with ETEC strain H10407 and in subjects rechallenged with the homologous organism. IgA responses to lipopolysaccharide (LPS), heat-labile toxin B subunit (LTB), and colonization factor antigen I (CFA/I) in antibody in lymphocyte supernatant (ALS), feces, lavage fluid, and saliva samples were evaluated. In all assay comparisons, ALS was the most sensitive indicator of a local immune response, but serum IgA was also a useful indirect marker of immune response to oral antigens. Volunteers challenged and then rechallenged with strain H10407 were protected from illness following rechallenge. Comparing mucosal antibody responses after primary and homologous rechallenge, protection against disease was reflected in reduced antibody responses to key ETEC antigens and in reduced fecal shedding of the H10407 challenge strain. Subjects challenged with strain H10407 mounted stronger antibody responses to LPS and LTB than subjects in the rechallenge group, while responses to CFA/I in the rechallenge group were higher than in the challenge group. We anticipate that this study will help provide an immunological benchmark for the evaluation of ETEC vaccines and immunization regimens in the future.

  10. Development of fowl cholera vaccine: I. Protection of Pasteurella multocida local isolate vaccine against challenge of homologous and heterologous strains.

    Directory of Open Access Journals (Sweden)

    Supar

    2001-03-01

    Full Text Available Pasteurella multocida locally isolated from chicken and ducks (BCC 299, BCC 2331, DY1, DY2, 12TG, 15TG andimported strains (BCC 1359, 1362; HEDDLESTON group 1 and 6 respectively had been tested for its pathogenicity in theprevious study. The aims of this experiment were to study the preparation of local isolate pasteurellosis vaccines and to determine the protective effect of that vaccines in chicken against the highly pathogenic local isolates of P. multocida. Killed monovalent, bivalent and polyvalent pasteurellosis vaccines were prepared and each was adjunvanted with aluminum hydroxide gel at a final concentration of 1.5% and the cell concentration was equal to the No 10 of MacFarland tube standard. Each of the vaccine prepared was used to vaccinated on a group of six week old of layer chicken (8 per group. Each chicken was subcutaneously injected with 0.2 ml of vaccine, four weeks later each was boostered with similar vaccine with the same dose. Two weeks after giving the boostered vaccine each group of chicken were challenged, half with life bacterium of P. Multocida BCC 2331 and other with DY2. Any chick which survive after challenge was designated as protected by vaccination. Before vaccination 1 ml of blood was drawn from each of chicken and then two weeks apart up to challenge. Serum from each sample was separated and kept in deep freeze until tested by enzyme-linked immunosorbent assay (ELISA. Chicken vaccinated with killed whole cell P. multocida vaccines of monovalent (BCC 2331 or DY2 and bivalent (BCC 2331 + DY2 were protected against challenge with live bacterium of either BCC 2331 or DY2 at rate 67-100%. There was no protection in chicken vaccinated with either BCC 299, DY1, 12TG, 15TG, BCC 1359, or 1362 killed vaccine. Similarly no protection of chicken vaccinated with either DY1 + BCC299, 12TG + 15TG or BCC 1359 + BCC 1362 bivalent vaccines. The protection rate of the polyvalent local isolate vaccine was at average 50-75%. All

  11. 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

  12. Exchange rate targeting in New Member States of the European Union: New Times, New Challenges

    Directory of Open Access Journals (Sweden)

    Alina Georgeta Glod

    2009-06-01

    Full Text Available This article points out some of the challenges of the monetary authorities in countries which have fixedexchange rate arrangement. In the current crisis environment, the Baltic States and Bulgaria seem to have moreproblems than solutions. Though, the situation is not very appealing now and in the future, they could exploit thestatus of being pegged to euro, by adhering sooner to the euro zone than the Visegrad Group if they urgentlycorrect the financial-budgetary and external imbalances.

  13. Targeted proteome analysis of single-gene deletion strains of Saccharomyces cerevisiae lacking enzymes in the central carbon metabolism

    Science.gov (United States)

    Kinoshita, Syohei; Nishino, Shunsuke; Tomita, Atsumi; Shimizu, Hiroshi

    2017-01-01

    Central carbon metabolism is controlled by modulating the protein abundance profiles of enzymes that maintain the essential systems in living organisms. In this study, metabolic adaptation mechanisms in the model organism Saccharomyces cerevisiae were investigated by direct determination of enzyme abundance levels in 30 wild type and mutant strains. We performed a targeted proteome analysis using S. cerevisiae strains that lack genes encoding the enzymes responsible for central carbon metabolism. Our analysis revealed that at least 30% of the observed variations in enzyme abundance levels could be explained by global regulatory mechanisms. A enzyme-enzyme co-abundance analysis revealed that the abundances of enzyme proteins involved in the trehalose metabolism and glycolysis changed in a coordinated manner under the control of the transcription factors for global regulation. The remaining variations were derived from local mechanisms such as a mutant-specific increase in the abundances of remote enzymes. The proteome data also suggested that, although the functional compensation of the deficient enzyme was attained by using more resources for protein biosynthesis, available resources for the biosynthesis of the enzymes responsible for central metabolism were not abundant in S. cerevisiae cells. These results showed that global and local regulation of enzyme abundance levels shape central carbon metabolism in S. cerevisiae by using a limited resource for protein biosynthesis. PMID:28241048

  14. The identification of enzyme targets for the optimization of a valine producing Corynebacterium glutamicum strain using a kinetic model.

    Science.gov (United States)

    Magnus, Jørgen Barsett; Oldiges, Marco; Takors, Ralf

    2009-01-01

    The enzyme targets for the rational optimization of a Corynebacterium glutamicum strain constructed for valine production are identified by analyzing the control of flux in the valine/leucine pathway. The control analysis is based on measurements of the intracellular metabolite concentrations and on a kinetic model of the reactions in the investigated pathway. Data-driven and model-based methods are used and evaluated against each other. The approach taken gives a quantitative evaluation of the flux control and it is demonstrated how the understanding of flux control is used to reach specific recommendations for strain optimization. The flux control coefficients (FCCs) with respect to the valine excretion rate were calculated, and it was found that the control is distributed mainly between the acetohydroxyacid synthase enzyme (FCC = 0.32), the branched chain amino acid transaminase (FCC = 0.27), and the exporting translocase (FCC = 0.43). The availability of the precursor pyruvate has substantial influence on the valine flux, whereas the cometabolites are less important as demonstrated by the calculation of the respective response coefficients. The model is further used to make in-silico predictions of the change in valine flux following a change in enzyme level. A doubling of the enzyme level of valine translocase will result in an increase in valine flux of 31%. By optimizing the enzyme levels with respect to valine flux it was found that the valine flux can be increased by a factor 2.5 when the optimal enzyme levels are implemented.

  15. Generation of stable mutants and targeted gene deletion strains in Cryptococcus neoformans through electroporation.

    Science.gov (United States)

    Lin, Xiaorong; Chacko, Nadia; Wang, Linqi; Pavuluri, Yashwant

    2015-04-01

    Cryptococcus neoformans is the etiologic agent of cryptococcal meningitis that causes more than half a million deaths worldwide each year. This capsulated basidiomycetous yeast also serves as a model for micropathogenic studies. The ability to make stable mutants, either via ectopic integration or homologous recombination, has been accomplished using biolistic transformation. This technical advance has greatly facilitated the research on the basic biology and pathogenic mechanisms of this pathogen in the past two decades. However, biolistic transformation is costly, and its reproducibility varies widely. Here we found that stable ectopic integration or targeted gene deletion via homologous replacement could be accomplished through electroporative transformation. The stability of the transformants obtained through electroporation and the frequency of homologous replacement is highly dependent on the selective marker. A frequency of homologous recombination among the stable transformants obtained by electroporation is comparable to those obtained by biolistic transformation (∼10%) when dominant drug selection markers are used, which is much higher than what has been previously reported for electroporation when auxotrophic markers were used (0.001% to 0.1%). Furthermore, disruption of the KU80 gene or generation of gene deletion constructs using the split marker strategy, two approaches known to increase homologous replacement among transformants obtained through biolistic transformation, also increase the frequency of homologous replacement among transformants obtained through electroporation. Therefore, electroporation provides a low cost alternative for mutagenesis in Cryptococcus.

  16. Entericidin is required for a probiotic treatment (Enterobacter sp. strain C6-6) to protect trout from cold-water disease challenge.

    Science.gov (United States)

    Schubiger, Carla B; Orfe, Lisa H; Sudheesh, Ponnerassery S; Cain, Kenneth D; Shah, Devendra H; Call, Douglas R

    2015-01-01

    Flavobacterium psychrophilum causes bacterial cold-water disease in multiple fish species, including salmonids. An autochthonous Enterobacter strain (C6-6) inhibits the in vitro growth of F. psychrophilum, and when ingested as a putative probiotic, it provides protection against injection challenge with F. psychrophilum in rainbow trout. In this study, low-molecular-mass (≤3 kDa) fractions from both Enterobacter C6-6 and Escherichia coli K-12 culture supernatants inhibited the growth of F. psychrophilum. The ≤3-kDa fraction from Enterobacter C6-6 was analyzed by SDS-PAGE, and subsequent tandem mass spectroscopy identified EcnB, which is a small membrane lipoprotein that is a putative pore-forming toxin. Agar plate diffusion assays demonstrated that ecnAB knockout strains of both Enterobacter C6-6 and E. coli K-12 no longer inhibited F. psychrophilum (P ) and the wild-type strain (C6-6) were added to the fish diet every day for 38 days. On day 11, the fish were challenged by injection with a virulent strain of F. psychrophilum (CSF 259-93). Fish that were fed C6-6 had significantly longer survival than fish fed the ecnAB knockout strain (P Enterobacter C6-6, and it may present new opportunities for therapeutic and prophylactic treatments against similarly susceptible pathogens.

  17. Targeting the non-structural protein 1 from dengue virus to a dendritic cell population confers protective immunity to lethal virus challenge.

    Science.gov (United States)

    Henriques, Hugo R; Rampazo, Eline V; Gonçalves, Antonio J S; Vicentin, Elaine C M; Amorim, Jaime H; Panatieri, Raquel H; Amorim, Kelly N S; Yamamoto, Marcio M; Ferreira, Luís C S; Alves, Ada M B; Boscardin, Silvia B

    2013-01-01

    Dengue is the most prevalent arboviral infection, affecting millions of people every year. Attempts to control such infection are being made, and the development of a vaccine is a World Health Organization priority. Among the proteins being tested as vaccine candidates in preclinical settings is the non-structural protein 1 (NS1). In the present study, we tested the immune responses generated by targeting the NS1 protein to two different dendritic cell populations. Dendritic cells (DCs) are important antigen presenting cells, and targeting proteins to maturing DCs has proved to be an efficient means of immunization. Antigen targeting is accomplished by the use of a monoclonal antibody (mAb) directed against a DC cell surface receptor fused to the protein of interest. We used two mAbs (αDEC205 and αDCIR2) to target two distinct DC populations, expressing either DEC205 or DCIR2 endocytic receptors, respectively, in mice. The fusion mAbs were successfully produced, bound to their respective receptors, and were used to immunize BALB/c mice in the presence of polyriboinosinic: polyribocytidylic acid (poly (I:C)), as a DC maturation stimulus. We observed induction of strong anti-NS1 antibody responses and similar antigen binding affinity irrespectively of the DC population targeted. Nevertheless, the IgG1/IgG2a ratios were different between mouse groups immunized with αDEC-NS1 and αDCIR2-NS1 mAbs. When we tested the induction of cellular immune responses, the number of IFN-γ producing cells was higher in αDEC-NS1 immunized animals. In addition, mice immunized with the αDEC-NS1 mAb were significantly protected from a lethal intracranial challenge with the DENV2 NGC strain when compared to mice immunized with αDCIR2-NS1 mAb. Protection was partially mediated by CD4(+) and CD8(+) T cells as depletion of these populations reduced both survival and morbidity signs. We conclude that targeting the NS1 protein to the DEC205(+) DC population with poly (I:C) opens

  18. Targeting the non-structural protein 1 from dengue virus to a dendritic cell population confers protective immunity to lethal virus challenge.

    Directory of Open Access Journals (Sweden)

    Hugo R Henriques

    Full Text Available Dengue is the most prevalent arboviral infection, affecting millions of people every year. Attempts to control such infection are being made, and the development of a vaccine is a World Health Organization priority. Among the proteins being tested as vaccine candidates in preclinical settings is the non-structural protein 1 (NS1. In the present study, we tested the immune responses generated by targeting the NS1 protein to two different dendritic cell populations. Dendritic cells (DCs are important antigen presenting cells, and targeting proteins to maturing DCs has proved to be an efficient means of immunization. Antigen targeting is accomplished by the use of a monoclonal antibody (mAb directed against a DC cell surface receptor fused to the protein of interest. We used two mAbs (αDEC205 and αDCIR2 to target two distinct DC populations, expressing either DEC205 or DCIR2 endocytic receptors, respectively, in mice. The fusion mAbs were successfully produced, bound to their respective receptors, and were used to immunize BALB/c mice in the presence of polyriboinosinic: polyribocytidylic acid (poly (I:C, as a DC maturation stimulus. We observed induction of strong anti-NS1 antibody responses and similar antigen binding affinity irrespectively of the DC population targeted. Nevertheless, the IgG1/IgG2a ratios were different between mouse groups immunized with αDEC-NS1 and αDCIR2-NS1 mAbs. When we tested the induction of cellular immune responses, the number of IFN-γ producing cells was higher in αDEC-NS1 immunized animals. In addition, mice immunized with the αDEC-NS1 mAb were significantly protected from a lethal intracranial challenge with the DENV2 NGC strain when compared to mice immunized with αDCIR2-NS1 mAb. Protection was partially mediated by CD4(+ and CD8(+ T cells as depletion of these populations reduced both survival and morbidity signs. We conclude that targeting the NS1 protein to the DEC205(+ DC population with poly (I

  19. 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.

  20. Acute coronary syndromes. Challenging accepted post-MI serum potassium targets.

    Science.gov (United States)

    van Diepen, Sean; Granger, Christopher B

    2012-02-28

    On the basis of high-quality observational data, Goyal et al. have found that serum potassium levels <3.5 mmol/l or ≥4.5 mmol/l are associated with increased in-hospital mortality in patients with acute myocardial infarction. We discuss whether target potassium levels in clinical practice and guidelines should be changed to 3.5–4.5 mmol/l.

  1. Understanding and targeting cancer stem cells:therapeutic implications and challenges

    Institute of Scientific and Technical Information of China (English)

    Ke CHEN; Ying-hui HUANG; Ji-long CHEN

    2013-01-01

    Cancer stem cells (CSCs) have been identified as rare cell populations in many cancers,including leukemia and solid tumors.Accumulating evidence has suggested that CSCs are capable of self-renewal and differentiation into various types of cancer cells.Aberrant regulation of gene expression and some signaling pathways has been observed in CSCs compared to other tumor cells.CSCs are thought to be responsible for cancer initiation,progression,metastasis,recurrence and drug resistance.The CSC hypothesis has recently attracted much attention due to the potential for discovery and development of CSC-related therapies and the identification of key molecules involved in controlling the unique properties of CSC populations.Over the past several years,a tremendous amount of effort has been invested in the development of new drugs,such as nanomedicines,that can take advantage of the "Achilles'heel" of CSCs by targeting cell-surface molecular markers or various signaling pathways.Novel compounds and therapeutic strategies that selectively target CSCs have been identified,some of which have been evaluated in preclinical and clinical studies.In this article,we review new findings related to the investigation of the CSC hypothesis,and discuss the crucial pathways involved in regulating the development of CSC populations and the advances in studies of drug resistance.In addition,we review new CSC-targeted therapeutic strategies aiming to eradicate malignancies.

  2. [Interdisciplinary and individualized therapy of prostate cancer : International prostate cancer symposium Bonn 2013 - challenges and targets].

    Science.gov (United States)

    Schwardt, M; Debus, J; Feick, G; Hadaschik, B; Hohenfellner, M; Schüle, R; Zacharias, J-P; Combs, S E

    2015-11-01

    Multimodal treatment of prostate cancer is based on specific staging via imaging, clinical parameters, tumor markers and histopathological grading. Risk-adapted therapy encompasses wait and see, active surveillance, surgical intervention, radiotherapy and hormone therapy. Some patients also need a combination of these treatment options. Even though clinical parameters guide the treatment plan, patient wishes and preferences are incorporated. Against this background leading basic research scientists, urologists, radiotherapists, epidemiologists and members of other associated disciplines discussed state of the art treatment concepts, innovative trial designs and translational research projects at the international meeting "Challenges and Chances in Prostate Cancer Research" organized by the German Cancer Aid (Deutsche Krebshilfe).

  3. Evaluation of Rapid Molecular Detection Assays for Salmonella in Challenging Food Matrices at Low Inoculation Levels and Using Difficult-to-Detect Strains.

    Science.gov (United States)

    Ryan, Gina; Roof, Sherry; Post, Laurie; Wiedmann, Martin

    2015-09-01

    Assays for detection of foodborne pathogens are generally initially evaluated for performance in validation studies carried out according to guidelines provided by validation schemes (e.g., AOAC International or the International Organization for Standardization). End users often perform additional validation studies to evaluate the performance of assays in specific matrices (e.g., specific foods or raw material streams of interest) and with specific pathogen strains. However, these types of end-user validations are typically not well defined. This study was conducted to evaluate a secondary end user validation of four AOAC-validated commercial rapid detection assays (an isothermal nucleic acid amplification, an immunoassay, and two PCR-based assays) for their ability to detect Salmonella in two challenging matrices (dry pet food and dark chocolate). Inclusivity was evaluated with 68 diverse Salmonella strains at low population levels representing the limit of detection (LOD) for each assay. One assay detected all strains at the LOD, two assays detected multiple strains only at 10 times the LOD, and the fourth assay failed to detect two strains (Salmonella bongori and S. enterica subsp. houtenae) even at 1,000 times the LOD; this assay was not further evaluated. The three remaining assays were subsequently evaluated for their ability to detect five selected Salmonella strains in food samples contaminated at fractional levels. Unpaired comparisons revealed no significant difference between the results for each given assay and the results obtained with the reference assay. However, analysis of paired culture-confirmed results revealed assay false-negative rates of 4 to 26% for dry pet food and 12 to 16% for dark chocolate. Overall, our data indicate that rapid assays may have high false-negative rates when performance is evaluated under challenging conditions, including low-moisture matrices, strains that are difficult to detect, injured cells, and low inoculum

  4. Structure of an IgNAR-AMA1 complex: targeting a conserved hydrophobic cleft broadens malarial strain recognition.

    Science.gov (United States)

    Henderson, Kylie A; Streltsov, Victor A; Coley, Andrew M; Dolezal, Olan; Hudson, Peter J; Batchelor, Adrian H; Gupta, Aditi; Bai, Tao; Murphy, Vincent J; Anders, Robin F; Foley, Michael; Nuttall, Stewart D

    2007-11-01

    Apical membrane antigen 1 (AMA1) is essential for invasion of erythrocytes and hepatocytes by Plasmodium parasites and is a leading malarial vaccine candidate. Although conventional antibodies to AMA1 can prevent such invasion, extensive polymorphisms within surface-exposed loops may limit the ability of these AMA1-induced antibodies to protect against all parasite genotypes. Using an AMA1-specific IgNAR single-variable-domain antibody, we performed targeted mutagenesis and selection against AMA1 from three P. falciparum strains. We present cocrystal structures of two antibody-AMA1 complexes which reveal extended IgNAR CDR3 loops penetrating deep into a hydrophobic cleft on the antigen surface and contacting residues conserved across parasite species. Comparison of a series of affinity-enhancing mutations allowed dissection of their relative contributions to binding kinetics and correlation with inhibition of erythrocyte invasion. These findings provide insights into mechanisms of single-domain antibody binding, and may enable design of reagents targeting otherwise cryptic epitopes in pathogen antigens.

  5. 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.

  6. Challenges in Targeting a Basic Helix-Loop-Helix Transcription Factor with Hydrocarbon-Stapled Peptides.

    Science.gov (United States)

    Edwards, Amanda L; Meijer, Dimphna H; Guerra, Rachel M; Molenaar, Remco J; Alberta, John A; Bernal, Federico; Bird, Gregory H; Stiles, Charles D; Walensky, Loren D

    2016-11-18

    Basic helix-loop-helix (bHLH) transcription factors play critical roles in organism development and disease by regulating cell proliferation and differentiation. Transcriptional activity, whether by bHLH homo- or heterodimerization, is dependent on protein-protein and protein-DNA interactions mediated by α-helices. Thus, α-helical decoys have been proposed as potential targeted therapies for pathologic bHLH transcription. Here, we developed a library of stabilized α-helices of OLIG2 (SAH-OLIG2) to test the capacity of hydrocarbon-stapled peptides to disrupt OLIG2 homodimerization, which drives the development and chemoresistance of glioblastoma multiforme, one of the deadliest forms of human brain cancer. Although stapling successfully reinforced the α-helical structure of bHLH constructs of varying length, sequence-specific dissociation of OLIG2 dimers from DNA was not achieved. Re-evaluation of the binding determinants for OLIG2 self-association and stability revealed an unanticipated role of the C-terminal domain. These data highlight potential pitfalls in peptide-based targeting of bHLH transcription factors given the liabilities of their positively charged amino acid sequences and multifactorial binding determinants.

  7. Aldose Reductase as a Drug Target for Treatment of Diabetic Nephropathy: Promises and Challenges.

    Science.gov (United States)

    El Gamal, Heba; Munusamy, Shankar

    2016-11-28

    Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes mellitus and the leading cause of end stage renal disease. One of the key pathways activated in DN is the polyol pathway, in which glucose is converted to sorbitol (a relatively non-metabolizable sugar) by the enzyme aldose reductase (AR). Shunting of glucose into this pathway causes disruption to glucose metabolism and subsequently damages the tissues via increased oxidative stress, protein kinase c activation and production of advanced glycation end products (AGE) in the kidney. This review aims to provide a comprehensive overview of the AR enzyme structure, substrate specificity and topology in normal physiology; to elaborate on the deleterious effects of AR activation in DN; and to summarize the potential therapeutic benefits and major challenges associated with AR inhibition in patients with DN.

  8. Targeting cytokine/chemokine receptors: a challenge for molecular nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Signore, A. [Nuclear Medicine Unit, Department of Clinical Sciences, Policlinico Umberto I, University ' ' La Sapienza' ' , Via del Policlinico 155, 00161 Roma (Italy); Chianelli, M. [Nuclear Medicine, ' ' Regina Apostolorum' ' Hospital, Albano (Roma) (Italy); Bei, R.; Modesti, A. [Department of Experimental Medicine and Biochemical Sciences, University ' ' Tor Vergata' ' , Roma (Italy); Oyen, W. [Department of Nuclear Medicine, University Medical Center, Nijmegen (Netherlands)

    2003-01-01

    Radiolabelled cytokines and chemokines are a group of radiopharmaceuticals that, by highlighting in vivo the binding to specific high-affinity receptors expressed on selected cell populations, allow the molecular and functional characterisation of immune-mediated processes Recently, several authors have described the use of radiolabelled cytokines and chemokines not only for imaging of inflammation and infection, but also as an approach to study in vivo the biology of primary and metastatic cancer cells. The latter avenue of research has been pursued particularly to help oncologists in therapeutic decision making and to follow up the efficacy of new immune therapies. In this paper we describe the characteristics of cytokines and chemokines, focussing on their role as radiopharmaceuticals for the imaging of cancer cells in vivo, a new challenge for molecular nuclear medicine. (orig.)

  9. Neutralization of Diverse Human Cytomegalovirus Strains Conferred by Antibodies Targeting Viral gH/gL/pUL128-131 Pentameric Complex

    Science.gov (United States)

    Ha, Sha; Li, Fengsheng; Troutman, Matthew C.; Freed, Daniel C.; Tang, Aimin; Loughney, John W.; Wang, I-Ming; Vlasak, Josef; Nickle, David C.; Rustandi, Richard R.; Hamm, Melissa; DePhillips, Pete A.; Zhang, Ningyan; McLellan, Jason S.; Zhu, Hua; Adler, Stuart P.; McVoy, Michael A.; An, Zhiqiang

    2017-01-01

    ABSTRACT Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection, and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex glycoprotein H (gH)/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross-neutralize the field strains of HCMV, remains a challenge. In this study, with a panel of neutralizing antibodies from three healthy human donors with natural HCMV infection or a vaccinated animal, we mapped eight sites on the dominant virus-neutralizing antigen—the pentameric complex of glycoprotein H (gH), gL, and pUL128, pUL130, and pUL131. By evaluating the site-specific antibodies in vaccine immune sera, we demonstrated that vaccination elicited functional antiviral antibodies to multiple neutralizing sites in rhesus macaques, with quality attributes comparable to those of CMV hyperimmune globulin. Furthermore, these immune sera showed antiviral activities against a panel of genetically distinct HCMV clinical isolates. These results highlighted the importance of understanding the quality of vaccine-induced antibody responses, which includes not only the neutralizing potency in key cell types but also the ability to protect against the genetically diverse field strains. IMPORTANCE HCMV is the leading cause of congenital viral infection, and development of a preventive vaccine is a high public health priority. To understand the strain coverage of vaccine-induced immune responses in comparison with natural immunity, we used a panel of broadly neutralizing antibodies to identify the immunogenic sites of a dominant viral antigen—the pentameric complex. We further demonstrated that following vaccination of a replication

  10. 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

  11. Challenges of Sustaining the International Space Station Through 2020 and Beyond: Reassessing Confidence Targets for System Availability

    Science.gov (United States)

    Lutomski, Michael G.; Carter-Journet, Katrina; Anderson, Leif; Box, Neil; Harrington, Sean; Jackson, David; DiFilippo, Denise

    2012-01-01

    The International Space Station (ISS) was originally designed to operate until 2015 with a plan for deorbiting the ISS in 2016. Currently, the international partnership has agreed to extend the operations until 2020 and discussions are underway to extend the life even further to 2028. Each partner is responsible for the sustaining engineering, sparing, and maintenance of their own segments. National Aeronautics and Space Administration's (NASA's) challenge is to purchase the needed number of spares to maintain the functional availability of the ISS systems necessary for the United States On-Orbit Segment s contribution. This presentation introduces an analytical approach to assessing uncertainty in ISS hardware necessary to extend the life of the vehicle. Some key areas for consideration are: establishing what confidence targets are required to ensure science can be continuously carried out on the ISS, defining what confidence targets are reasonable to ensure vehicle survivability, considering what is required to determine if the confidence targets are too high, and whether sufficient number of spares are purchased. The results of the analysis will provide a methodological basis for reassessing vehicle subsystem confidence targets. This analysis compares the probability of existing spares exceeding the total expected unit demand of the Orbital Replacement Unit (ORU) in functional hierarchies approximating the vehicle subsystems. In cases where the functional hierarchies' availability does not meet subsystem confidence targets, the analysis will further identify which ORUs may require additional spares to extend the life of the ISS. The resulting probability is dependent upon hardware reliability estimates. However, the ISS hardware fleet carries considerable epistemic uncertainty which must be factored into the development and execution of sparing risk postures. In addition, it is also recognized that uncertainty in the assessment is due to disconnects between

  12. The challenge of treating obesity: the endocannabinoid system as a potential target.

    Science.gov (United States)

    Isoldi, Kathy Keenan; Aronne, Louis J

    2008-05-01

    Obesity and cardiometabolic risk, or the metabolic syndrome, continue to be major public health concerns. To date, treatment with lifestyle and pharmacotherapy interventions has resulted in limited efficacy in reversing the upward trend in this present-day health crisis. Research reveals that a modest 5% to 10% weight loss results in substantial improvement in health. While obtaining modest weight loss is often achievable, maintaining lost weight is challenging. Research has recently improved our understanding of several endogenous pathways that influence body weight regulation and disease risk. The endocannabinoid system has been found to regulate appetite and energy expenditure, as well as lipid and glucose metabolism. Interest in blocking stimulation of this pathway to aid weight loss and reduce cardiometabolic risk factor development is an area of interest and research. This article reviews the mechanisms by which the endocannabinoid system is believed to influence body weight regulation and cardiometabolic risk factors, as well as the results of clinical trials investigating the safety and efficacy of a selective cannabinoid-1 receptor antagonist (rimonabant). Clinical trials investigating rimonabant treatment resulted in substantial reductions in body weight and markers for cardiometabolic risk in study participants. However, increases in adverse events were reported in the drug-treated group. Data regarding long-term benefit and adverse events from rimonabant treatment are being collected in several ongoing clinical trials. Rimonabant is currently available in 42 countries, but has not received United States Food and Drug Administration approval. Food and nutrition professionals play a pivotal role in tackling the current obesity crisis; it is essential that they understand the many physiological mechanisms regulating body weight. Emerging research data reveals pathways that influence appetite and energy metabolism, and this knowledge may form the foundation

  13. Potential seasonal ecological challenge of heat strain among Australian Aboriginal people practicing traditional subsistence methods: a computer simulation.

    Science.gov (United States)

    Ulijaszek, S J

    2001-11-01

    It has been largely accepted that Australian Aboriginal people practicing hunting and gathering traditionally underused their objective economic possibilities by working short hours relative to nonhunter-gatherer populations. However, the possibility that their subsistence quest might have been limited by potential heat strain has not been considered for Australian hunter-gatherers. In this article the influence of work and heat load on the potential for heat strain among adult male Australian Aboriginal people is modelled. The possibility that the short working day of Arnhem Land adults reported in the literature might reflect ecologically limited work scheduling by way of potential heat strain is examined. Three climatic regions of the North of Western Australia and the Northern Territory were identified, using data available from the Australian Bureau of Meteorology. Data from the months of January, April, July, and October were used with the United States Army Heat Strain Model, along with assumptions with respect to work load and time scheduling. Predictive modelling indicates that a late start to the working day could carry considerable risks of potential heat strain during the summer, when humidity and maximum daily temperature are highest for all three climatic regions, but especially in the tropical coastal region. While extended work times may have been needed to acquire adequate food under traditional conditions, work output could have been limited by potential heat strain under some conditions likely to have prevailed.

  14. 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

  15. Development of a sequence-characterized amplified region marker-targeted quantitative PCR assay for strain-specific detection of Oenococcus oeni during wine malolactic fermentation.

    Science.gov (United States)

    Solieri, Lisa; Giudici, Paolo

    2010-12-01

    Control over malolactic fermentation (MLF) is a difficult goal in winemaking and needs rapid methods to monitor Oenococcus oeni malolactic starters (MLS) in a stressful environment such as wine. In this study, we describe a novel quantitative PCR (QPCR) assay enabling the detection of an O. oeni strain during MLF without culturing. O. oeni strain LB221 was used as a model to develop a strain-specific sequence-characterized amplified region (SCAR) marker derived from a discriminatory OPA20-based randomly amplified polymorphic DNA (RAPD) band. The 5' and 3' flanking regions and the copy number of the SCAR marker were characterized using inverse PCR and Southern blotting, respectively. Primer pairs targeting the SCAR sequence enabled strain-specific detection without cross amplification of other O. oeni strains or wine species of lactic acid bacteria (LAB), acetic acid bacteria (AAB), and yeasts. The SCAR-QPCR assay was linear over a range of cell concentrations (7 log units) and detected as few as 2.2 × 10(2) CFU per ml of red wine with good quantification effectiveness, as shown by the correlation of QPCR and plate counting results. Therefore, the cultivation-independent monitoring of a single O. oeni strain in wine based on a SCAR marker represents a rapid and effective strain-specific approach. This strategy can be adopted to develop easy and rapid detection techniques for monitoring the implantation of inoculated O. oeni MLS on the indigenous LAB population, reducing the risk of unsuccessful MLF.

  16. Differential Gene Expression of Three Gene Targets among Persistent and Nonpersistent Listeria monocytogenes Strains in the Presence or Absence of Benzethonium Chloride.

    Science.gov (United States)

    Mazza, Roberta; Mazzette, Rina; McAuliffe, Olivia; Jordan, Kieran; Fox, Edward M

    2015-08-01

    Persistence of Listeria monocytogenes strains in food processing environments remains relatively common but is difficult to control. Understanding the basis for such persistence represents an important step in the potential control or eradication of this pathogen from these environments. In this study, reverse transcription PCR was used to determine the relative and absolute expression of selected gene targets (pocR, eutJ, and qacH) among five persistent and four presumed nonpersistent L. monocytogenes strains. The quantification of these genes as markers for the persistent phenotype and the effect of benzethonium chloride (BZT) on their expression was investigated. Although no markers correlated with the ability of strains to persist in food processing facilities were found, expression of pocR was upregulated in three of the five persistent strains, in contrast to the four presumed nonpersistent strains, which showed down-regulation of this gene. These results provide further knowledge of the differential expression of genes of persistent and presumed nonpersistent strains of L. monocytogenes grown in the presence or absence of BZT and identifies upregulation of pocR as a potential response of persistent strains of L. monocytogenes to exposure to BZT.

  17. First data on Eurasian wild boar response to oral immunization with BCG and challenge with a Mycobacterium bovis field strain.

    Science.gov (United States)

    Ballesteros, C; Garrido, J M; Vicente, J; Romero, B; Galindo, R C; Minguijón, E; Villar, M; Martín-Hernando, M P; Sevilla, I; Juste, R; Aranaz, A; de la Fuente, J; Gortázar, C

    2009-11-12

    The Eurasian wild boar (Sus scrofa) is considered a reservoir for bovine tuberculosis (bTB) caused by Mycobacterium bovis and closely related members of the Mycobacterium tuberculosis complex in south-central Spain. The vaccination of wildlife with BCG offers an alternative to culling and to movement restriction for the control of bTB among wildlife reservoirs. In this study, we hypothesized that oral BCG immunization of wild boar would affect the expression of immunoregulatory genes and confer protection against M. bovis. Three groups were used to describe the infection, pathological findings and gene expression profiles in wild boar: BCG-vaccinated and M. bovis-challenged (vaccinated challenged group; N=6), non-vaccinated and M. bovis-challenged (non-vaccinated challenged group; N=4), and non-vaccinated and mock-infected (control group; N=2) animals. M. bovis was isolated from 50% (3/6) and 75% (3/4) of vaccinated challenged and non-vaccinated challenged animals, respectively. All four wild boar from the non-vaccinated challenged group developed bTB-compatible lesions 114 days after challenge. In contrast, only 50% of vaccinated challenged wild boar developed lesions. The PBMC mRNA levels of IL4, RANTES, C3, IFN-gamma and methylmalonyl-CoA mutase (MUT) were analyzed at several days post-vaccination (dpi). When vaccinated challenged animals were compared to controls, all five genes were significantly upregulated at the time of M. bovis infection at 186dpi but IFN-gamma levels were also upregulated at 11 and 46dpi. The C3 and MUT mRNA levels were higher at 46dpi, and 11 and 186dpi, respectively, in vaccinated protected wild boar when compared to non-vaccinated challenged animals. At the end of the experiment (300dpi), the mRNA levels of selected genes were lower in non-vaccinated challenged animals when compared to control wild boar. Exposing wild boar to a dose of 10(4)cfu of M. bovis by the oropharyngeal route is an adequate protocol to produce an infection model

  18. Salmonella enterica serovar typhimurium trxA mutants are protective against virulent challenge and induce less inflammation than the live-attenuated vaccine strain SL3261.

    Science.gov (United States)

    Peters, S E; Paterson, G K; Bandularatne, E S D; Northen, H C; Pleasance, S; Willers, C; Wang, J; Foote, A K; Constantino-Casas, F; Scase, T J; Blacklaws, B A; Bryant, C E; Mastroeni, P; Charles, I G; Maskell, D J

    2010-01-01

    In Salmonella enterica serovar Typhimurium, trxA encodes thioredoxin 1, a small, soluble protein with disulfide reductase activity, which catalyzes thiol disulfide redox reactions in a variety of substrate proteins. Thioredoxins are involved as antioxidants in defense against oxidative stresses, such as exposure to hydrogen peroxide and hydroxyl radicals. We have made a defined, complete deletion of trxA in the mouse-virulent S. Typhimurium strain SL1344 (SL1344 trxA), replacing the gene with a kanamycin resistance gene cassette. SL1344 trxA was attenuated for virulence in BALB/c mice by the oral and intravenous routes and when used in immunization experiments provided protection against challenge with the virulent parent strain. SL1344 trxA induced less inflammation in murine spleens and livers than SL3261, the aroA mutant, live attenuated vaccine strain. The reduced splenomegaly observed following infection with SL1344 trxA was partially attributed to a reduction in the number of both CD4(+) and CD8(+) T cells and B lymphocytes in the spleen and reduced infiltration by CD11b(+) cells into the spleen compared with spleens from mice infected with SL3261. This less severe pathological response indicates that a trxA mutation might be used to reduce reactogenicity of live attenuated vaccine strains. We tested this by deleting trxA in SL3261. SL3261 trxA was also less inflammatory than SL3261 but was slightly less effective as a vaccine strain than either the SL3261 parent strain or SL1344 trxA.

  19. Efficacy of dart or booster vaccination with strain RB51 in protecting bison against experimental Brucella abortus challenge

    Science.gov (United States)

    Vaccination is an effective tool for reducing the prevalence of brucellosis in natural hosts. In this study, we characterized the efficacy of the Brucella abortus strain RB51 (RB51) vaccine in bison when delivered by single intramuscular vaccination (Hand RB51), single pneumatic dart delivery (Dart ...

  20. The Acceptor Side of Photosystem II Is the Initial Target of Nitrite Stress in Synechocystis sp. Strain PCC 6803.

    Science.gov (United States)

    Zhang, Xin; Ma, Fei; Zhu, Xi; Zhu, Junying; Rong, Junfeng; Zhan, Jiao; Chen, Hui; He, Chenliu; Wang, Qiang

    2017-02-01

    Nitrite, a common form of inorganic nitrogen (N), can be used as a nitrogen source through N assimilation. However, high levels of nitrite depress photosynthesis in various organisms. In this study, we investigated which components of the photosynthetic electron transfer chain are targeted by nitrite stress in Synechocystis sp. strain PCC 6803 cells. Measurements of whole-chain and photosystem II (PSII)-mediated electron transport activities revealed that high levels of nitrite primarily impair electron flow in PSII. Changes in PSII activity in response to nitrite stress occurred in two distinct phases. During the first phase, which occurred in the first 3 h of nitrite treatment, electron transfer from the primary quinone acceptor (QA) to the secondary quinone acceptor (QB) was retarded, as indicated by chlorophyll (Chl) a fluorescence induction, S-state distribution, and QA(-) reoxidation tests. In the second phase, which occurred after 6 h of nitrite exposure, the reaction center was inactivated and the donor side of photosystem II was inhibited, as revealed by changes in Chl fluorescence parameters and thermoluminescence and by immunoblot analysis. Our data suggest that nitrite stress is highly damaging to PSII and disrupts PSII activity by a stepwise mechanism in which the acceptor side is the initial target. IMPORTANCE In our previous studies, an alga-based technology was proposed to fix the large amounts of nitrite that are released from NOX-rich flue gases and proved to be a promising industrial strategy for flue gas NOX bioremediation (W. Chen et al., Environ Sci Technol 50:1620-1627, 2016, https://doi.org/10.1021/acs.est.5b04696; X. Zhang et al., Environ Sci Technol 48:10497-10504, 2014, https://doi.org/10.1021/es5013824). However, the toxic effects of high concentrations of nitrite on algal cells remain obscure. The analysis of growth rates, photochemistry, and protein profiles in our study provides important evidence that the inhibition by nitrite occurs

  1. Protective efficacy of Marek's disease virus (MDV) CVI-988 CEF65 clone C against challenge infection with three very virulent MDV strains.

    Science.gov (United States)

    de Boer, G F; Groenendal, J E; Boerrigter, H M; Kok, G L; Pol, J M

    1986-01-01

    Comparative 50% protective dose (PD50) assays were performed using a plaque-purified preparation of Marek's disease virus (MDV) strain CVI-988 at the 65th chicken embryo fibroblast (CEF) passage level (MDV CVI-988 CEF65 clone C) and three commercial MD vaccines: herpesvirus of turkeys (HVT) FC126, MDV CVI-988 CEF35, and a bivalent vaccine composed of HVT FC126 and MDV SB-1. In addition, comparative PD50 assays were performed in groups of chickens with maternal antibody to each of the three vaccines. Three representatives of the newly emerged biovariant very virulent (vv) MDV strains-RB/1B, Tun, and Md5-were employed as challenge virus. The experiments made feasible the differentiation between virulent MDV and vvMDV strains, within serotype 1. Vaccination with CVI-988 clone C vaccine resulted in PD50 estimates of about 5 plaque-forming units (PFUs) against challenge infection with each of the three vvMDV strains. The PD50 estimate of CVI-988 clone C vaccine was 12-fold below the PD50 of HVT FC126. The protective synergism of bivalent vaccine, composed of HVT and SB-1, was confirmed by groups given the lowest vaccine doses. The bivalent vaccine, however, resulted in incomplete protection in groups given the highest vaccine doses. Homologous maternal antibodies to serotype 1 caused a fivefold increase in the PD50 estimate of CVI-988 clone C. Heterologous maternal antibodies against HVT did not interfere with efficacy of CVI-988 clone C vaccination. However, the combination of maternal antibodies against both HVT and SB-1 (serotypes 2 and 3) showed a strong adverse effect on CVI-988 clone C vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Proteome mining for the identification and in-silico characterization of putative drug targets of multi-drug resistant Clostridium difficile strain 630.

    Science.gov (United States)

    Lohani, Mohtashim; Dhasmana, Anupam; Haque, Shafiul; Wahid, Mohd; Jawed, Arshad; Dar, Sajad A; Mandal, Raju K; Areeshi, Mohammed Y; Khan, Saif

    2017-05-01

    Clostridium difficile is an enteric pathogen that causes approximately 20% to 30% of antibiotic-associated diarrhea. In recent years, there has been a substantial rise in the rate of C. difficile infections as well as the emergence of virulent and antibiotic resistant C. difficile strains. So, there is an urgent need for the identification of therapeutic potential targets and development of new drugs for the treatment and prevention of C. difficile infections. In the current study, we used a hybrid approach by combining sequence similarity-based approach and protein-protein interaction network topology-based approach to identify and characterize the potential drug targets of C. difficile. A total of 155 putative drug targets of C. difficile were identified and the metabolic pathway analysis of these putative drug targets using DAVID revealed that 46 of them are involved in 9 metabolic pathways. In-silico characterization of these proteins identified seven proteins involved in pathogen-specific peptidoglycan biosynthesis pathway. Three promising targets viz. homoserine dehydrogenase, aspartate-semialdehyde dehydrogenase and aspartokinase etc. were found to be involved in multiple enzymatic pathways of the pathogen. These 3 drug targets are of particular interest as they can be used for developing effective drugs against multi-drug resistant C. difficile strain 630 in the near future.

  3. Optimal strategies for virtual screening of induced-fit and flexible target in the 2015 D3R Grand Challenge

    Science.gov (United States)

    Ye, Zhaofeng; Baumgartner, Matthew P.; Wingert, Bentley M.; Camacho, Carlos J.

    2016-09-01

    Induced fit or protein flexibility can make a given structure less useful for docking and/or scoring. The 2015 Drug Design Data Resource (D3R) Grand Challenge provided a unique opportunity to prospectively test optimal strategies for virtual screening in these type of targets: heat shock protein 90 (HSP90), a protein with multiple ligand-induced binding modes; and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), a kinase with a large flexible pocket. Using previously known co-crystal structures, we tested predictions from methods that keep the receptor structure fixed and used (a) multiple receptor/ligand co-crystals as binding templates for minimization or docking ("close"), (b) methods that align or dock to a single receptor ("cross"), and (c) a hybrid approach that chose from multiple bound ligands as initial templates for minimization to a single receptor ("min-cross"). Pose prediction using our "close" models resulted in average ligand RMSDs of 0.32 and 1.6 Å for HSP90 and MAP4K4, respectively, the most accurate models of the community-wide challenge. On the other hand, affinity ranking using our "cross" methods performed well overall despite the fact that a fixed receptor cannot model ligand-induced structural changes,. In addition, "close" methods that leverage the co-crystals of the different binding modes of HSP90 also predicted the best affinity ranking. Our studies suggest that analysis of changes on the receptor structure upon ligand binding can help select an optimal virtual screening strategy.

  4. Response of ponies to adjuvanted EHV-1 whole virus vaccine and challenge with virus of the homologous strain.

    Science.gov (United States)

    Dolby, C A; Hannant, D; Mumford, J A

    1995-01-01

    Five yearling ponies were vaccinated with inactivated Equid herpesvirus type 1 (EHV-1) in Freund's complete adjuvant as a double emulsion and revaccinated 6 weeks later with EHV-1 in Freund's incomplete adjuvant. These ponies and three age-matched controls were challenged intra-nasally after a further 6 weeks with homologous live virus and monitored clinically, biologically and serologically. After challenge, clinical signs were mild in both groups. No cell-associated viraemias were detected in vaccinated ponies. Vaccination induced high levels of complement-fixing (CF) and virus-neutralizing (VN) antibody, and elicited a response to all major viral glycoproteins as shown by western blot analysis.

  5. The Genomic Scrapheap Challenge; Extracting Relevant Data from Unmapped Whole Genome Sequencing Reads, Including Strain Specific Genomic Segments, in Rats.

    Science.gov (United States)

    van der Weide, Robin H; Simonis, Marieke; Hermsen, Roel; Toonen, Pim; Cuppen, Edwin; de Ligt, Joep

    2016-01-01

    Unmapped next-generation sequencing reads are typically ignored while they contain biologically relevant information. We systematically analyzed unmapped reads from whole genome sequencing of 33 inbred rat strains. High quality reads were selected and enriched for biologically relevant sequences; similarity-based analysis revealed clustering similar to previously reported phylogenetic trees. Our results demonstrate that on average 20% of all unmapped reads harbor sequences that can be used to improve reference genomes and generate hypotheses on potential genotype-phenotype relationships. Analysis pipelines would benefit from incorporating the described methods and reference genomes would benefit from inclusion of the genomic segments obtained through these efforts.

  6. Functional complementation of Leishmania (Leishmania) amazonensis AP endonuclease gene (lamap) in Escherichia coli mutant strains challenged with DNA damage agents.

    Science.gov (United States)

    Verissimo-Villela, Erika; Kitahara-Oliveira, Milene Yoko; Reis, Ana Beatriz de Bragança Dos; Albano, Rodolpho Mattos; Da-Cruz, Alda Maria; Bello, Alexandre Ribeiro

    2016-05-01

    During its life cycle Leishmania spp. face several stress conditions that can cause DNA damages. Base Excision Repair plays an important role in DNA maintenance and it is one of the most conserved mechanisms in all living organisms. DNA repair in trypanosomatids has been reported only for Old World Leishmania species. Here the AP endonuclease from Leishmania (L.) amazonensis was cloned, expressed in Escherichia coli mutants defective on the DNA repair machinery, that were submitted to different stress conditions, showing ability to survive in comparison to the triple null mutant parental strain BW535. Phylogenetic and multiple sequence analyses also confirmed that LAMAP belongs to the AP endonuclease class of proteins.

  7. Functional complementation of Leishmania (Leishmania) amazonensis AP endonuclease gene (lamap) in Escherichia coli mutant strains challenged with DNA damage agents

    Science.gov (United States)

    Verissimo-Villela, Erika; Kitahara-Oliveira, Milene Yoko; dos Reis, Ana Beatriz de Bragança; Albano, Rodolpho Mattos; Da-Cruz, Alda Maria; Bello, Alexandre Ribeiro

    2016-01-01

    During its life cycle Leishmania spp. face several stress conditions that can cause DNA damages. Base Excision Repair plays an important role in DNA maintenance and it is one of the most conserved mechanisms in all living organisms. DNA repair in trypanosomatids has been reported only for Old World Leishmania species. Here the AP endonuclease from Leishmania (L.) amazonensis was cloned, expressed in Escherichia coli mutants defective on the DNA repair machinery, that were submitted to different stress conditions, showing ability to survive in comparison to the triple null mutant parental strain BW535. Phylogenetic and multiple sequence analyses also confirmed that LAMAP belongs to the AP endonuclease class of proteins. PMID:27223868

  8. 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.

  9. Sport psychiatry and psychotherapy. Mental strains and disorders in professional sports. Challenge and answer to societal changes.

    Science.gov (United States)

    Markser, Valentin Z

    2011-11-01

    Professional athletes are subject to massive somatic, social, and mental stress. Despite great public interest for athletic achievements, the emotional strains thereof are very poorly investigated and discussed. The main reason for this is the widespread assumption that only emotionally very strong athletes are able to compete at the highly professional level and therefore mental disorders do not exist in professional sports. But available research data about the prevalence of mental disorders in this area suggest that this hypothesis must be revised. With respect to depression and the overtraining syndrome, attempts have been made to demonstrate the difficulties with etiology, diagnostics, and treatment for sports psychiatry and psychotherapy. Scientifically, sport psychiatry and psychotherapy can be defined as a discipline, whose focus is the investigation, treatment, and prevention of the extreme and sports-specific emotional strains and disorders. In addition to sport psychology, which focuses mainly on performance enhancement, mental stress, and disorders can hereby be recognized, disorders be treated and the athletic performance sustained. With the foundation of the Task Force for Sports Psychiatry and Psychotherapy at the German Association for Psychiatry and Psychotherapy, scientific research, further education, prevention, and treatment for mental disorders in professional sports will be improved.

  10. Equid herpesvirus (EHV-1) live vaccine strain C147: efficacy against respiratory diseases following EHV types 1 and 4 challenges.

    Science.gov (United States)

    Patel, J R; Földi, J; Bateman, H; Williams, J; Didlick, S; Stark, R

    2003-03-20

    The temperature sensitive and host range mutant clone 147 of equine herpesvirus 1 (EHV-1) was assessed for its ability to protect conventional, susceptible adult horses against respiratory infection by EHV-1 and equine herpesvirus 4 (EHV-4). Intranasal (IN) vaccination with 5.2 log(10) TCID(50) did not cause adverse clinical reactions although a limited virus shedding and viraemia (leukocytes) was observed in 11 of 15 and 10 of 15 vaccinated horses respectively. All 15 vaccinated horses showed a significant seroresponse to both EHV-1 and EHV-4 for virus neutralising (VN) antibody. None of 14 control horses shed virus or became viraemic or seroconverted prior to challenge. EHV-1 challenge (dose 6.0 log(10)) 6 weeks after vaccination resulted in pyrexia in all eight control horses while eight vaccinated horses remained unaffected. Six control horses developed nasal discharge, five of which were mucopurulent nasal discharge (mean duration 3.2 days) which also occurred in four vaccinated horses for 1 day. All eight control horses shed challenge EHV-1 at a significantly higher level (group mean titre 2.6+/-0.4 log(10) TCID(50) per sample) and for much longer (mean duration 4.8+/-1.5 days) than that (group mean titre 1.4+/-0.8 log(10) TCID(50) per sample and mean duration 1.5+/-0.5 days) in six vaccinated horses. Furthermore, all eight control horses became viraemic (mean duration 2.9 days) but viraemia did not occur in eight vaccinated horses. Following EHV-1 challenge, all eight control horses showed a significant VN antibody rise to both EHV-1 and EHV-4 but this occurred in only one vaccinated horse and to EHV-4 only. In EHV-4 challenge (dose of 4.2 log(10) TCID(50)) of a separate pair of seven vaccinated and six control horses, 6 weeks after EHV-1 vaccination resulted in pyrexia (mean duration 2.3 days) and nasal discharge (mean duration 1.8 days) in three and five control horses respectively but the only reaction observed in the vaccinated group was nasal discharge

  11. Isolation and characterization of numerous novel phages targeting diverse strains of the ubiquitous and opportunistic pathogen Achromobacter xylosoxidans.

    Directory of Open Access Journals (Sweden)

    Johannes Wittmann

    Full Text Available The clinical relevance of nosocomially acquired infections caused by multi-resistant Achromobacter strains is rapidly increasing. Here, a diverse set of 61 Achromobacter xylosoxidans strains was characterized by MultiLocus Sequence Typing and Phenotype MicroArray technology. The strains were further analyzed in regard to their susceptibility to 35 antibiotics and to 34 different and newly isolated bacteriophages from the environment. A large proportion of strains were resistant against numerous antibiotics such as cephalosporines, aminoglycosides and quinolones, whereas piperacillin-tazobactam, ticarcillin, mezlocillin and imipenem were still inhibitory. We also present the first expanded study on bacteriophages of the genus Achromobacter that has been so far a blank slate with respect to phage research. The phages were isolated mainly from several waste water treatment plants in Germany. Morphological analysis of all of these phages by electron microscopy revealed a broad diversity with different members of the order Caudovirales, including the families Siphoviridae, Myoviridae, and Podoviridae. A broad spectrum of different host ranges could be determined for several phages that lysed up to 24 different and in part highly antibiotic resistant strains. Molecular characterisation by DNA restriction analysis revealed that all phages contain linear double-stranded DNA. Their restriction patterns display distinct differences underlining their broad diversity.

  12. Isolation and characterization of numerous novel phages targeting diverse strains of the ubiquitous and opportunistic pathogen Achromobacter xylosoxidans.

    Science.gov (United States)

    Wittmann, Johannes; Dreiseikelmann, Brigitte; Rohde, Christine; Rohde, Manfred; Sikorski, Johannes

    2014-01-01

    The clinical relevance of nosocomially acquired infections caused by multi-resistant Achromobacter strains is rapidly increasing. Here, a diverse set of 61 Achromobacter xylosoxidans strains was characterized by MultiLocus Sequence Typing and Phenotype MicroArray technology. The strains were further analyzed in regard to their susceptibility to 35 antibiotics and to 34 different and newly isolated bacteriophages from the environment. A large proportion of strains were resistant against numerous antibiotics such as cephalosporines, aminoglycosides and quinolones, whereas piperacillin-tazobactam, ticarcillin, mezlocillin and imipenem were still inhibitory. We also present the first expanded study on bacteriophages of the genus Achromobacter that has been so far a blank slate with respect to phage research. The phages were isolated mainly from several waste water treatment plants in Germany. Morphological analysis of all of these phages by electron microscopy revealed a broad diversity with different members of the order Caudovirales, including the families Siphoviridae, Myoviridae, and Podoviridae. A broad spectrum of different host ranges could be determined for several phages that lysed up to 24 different and in part highly antibiotic resistant strains. Molecular characterisation by DNA restriction analysis revealed that all phages contain linear double-stranded DNA. Their restriction patterns display distinct differences underlining their broad diversity.

  13. 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

  14. Targeting Non-Coding RNAs in Plants with the CRISPR-Cas Technology is a Challenge yet Worth Accepting.

    Science.gov (United States)

    Basak, Jolly; Nithin, Chandran

    2015-01-01

    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.

  15. 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.

  16. Loop-Mediated Isothermal Amplification Assay Targeting the MOMP Gene for Rapid Detection of Chlamydia psittaci Abortus Strain

    Directory of Open Access Journals (Sweden)

    Guo-Zhen Lin, Fu-Ying Zheng, Ji-Zhang Zhou, Guang-Hua Wang, Xiao-An Cao, Xiao-Wei Gong and Chang-Qing Qiu*

    2012-05-01

    Full Text Available For rapid detection of the Chlamydia psittaci abortus strain, a loop-mediated isothermal amplification (LAMP assay was developed and evaluated in this study. The primers for the LAMP assay were designed on the basis of the main outer membrane protein (MOMP gene sequence of C. psittaci. Analysis showed that the assay could detect the abortus strain of C. psittaci with adequate specificity. The sensitivity of the test was the same as that of the nested-conventional PCR and higher than that of chick embryo isolation. Testing of 153 samples indicated that the LAMP assay could detect the genome of the C. psittaci abortus strain effectively in clinical samples. This assay is a useful tool for rapid diagnosis of C. psittaci infection in sheep, swine and cattle.

  17. Targeted Amplicon Sequencing for Single-Nucleotide-Polymorphism Genotyping of Attaching and Effacing Escherichia coli O26:H11 Cattle Strains via a High-Throughput Library Preparation Technique.

    Science.gov (United States)

    Ison, Sarah A; Delannoy, Sabine; Bugarel, Marie; Nagaraja, Tiruvoor G; Renter, David G; den Bakker, Henk C; Nightingale, Kendra K; Fach, Patrick; Loneragan, Guy H

    2015-11-13

    Enterohemorrhagic Escherichia coli (EHEC) O26:H11, a serotype within Shiga toxin-producing E. coli (STEC) that causes severe human disease, has been considered to have evolved from attaching and effacing E. coli (AEEC) O26:H11 through the acquisition of a Shiga toxin-encoding gene. Targeted amplicon sequencing using next-generation sequencing technology of 48 phylogenetically informative single-nucleotide polymorphisms (SNPs) and three SNPs differentiating Shiga toxin-positive (stx-positive) strains from Shiga toxin-negative (stx-negative) strains were used to infer the phylogenetic relationships of 178 E. coli O26:H11 strains (6 stx-positive strains and 172 stx-negative AEEC strains) from cattle feces to 7 publically available genomes of human clinical strains. The AEEC cattle strains displayed synonymous SNP genotypes with stx2-positive sequence type 29 (ST29) human O26:H11 strains, while stx1 ST21 human and cattle strains clustered separately, demonstrating the close phylogenetic relatedness of these Shiga toxin-negative AEEC cattle strains and human clinical strains. With the exception of seven stx-negative strains, five of which contained espK, three stx-related SNPs differentiated the STEC strains from non-STEC strains, supporting the hypothesis that these AEEC cattle strains could serve as a potential reservoir for new or existing pathogenic human strains. Our results support the idea that targeted amplicon sequencing for SNP genotyping expedites strain identification and genetic characterization of E. coli O26:H11, which is important for food safety and public health.

  18. 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.

  19. 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.

  20. Challenges and advances in systems biology analysis of Bacillus spore physiology; molecular differences between an extreme heat resistant spore forming Bacillus subtilis food isolate and a laboratory strain.

    Science.gov (United States)

    Brul, Stanley; van Beilen, Johan; Caspers, Martien; O'Brien, Andrea; de Koster, Chris; Oomes, Suus; Smelt, Jan; Kort, Remco; Ter Beek, Alex

    2011-04-01

    Bacterial spore formers are prime organisms of concern in the food industry. Spores from the genus Bacillus are extremely stress resistant, most notably exemplified by high thermotolerance. This sometimes allows surviving spores to germinate and grow out to vegetative cells causing food spoilage and possible intoxication. Similar issues though more pending toward spore toxigenicity are observed for the anaerobic Clostridia. The paper indicates the nature of stress resistance and highlights contemporary molecular approaches to analyze the mechanistic basis of it in Bacilli. A molecular comparison between a laboratory strain and a food borne isolate, very similar at the genomic level to the laboratory strain but generating extremely heat resistant spores, is discussed. The approaches cover genome-wide genotyping, proteomics and genome-wide expression analyses studies. The analyses aim at gathering sufficient molecular information to be able to put together an initial framework for dynamic modelling of spore germination and outgrowth behaviour. Such emerging models should be developed both at the population and at the single spore level. Tools and challenges in achieving the latter are succinctly discussed.

  1. 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

  2. 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.

  3. Challenges of Sustaining the International Space Station through 2020 and Beyond: Including Epistemic Uncertainty in Reassessing Confidence Targets

    Science.gov (United States)

    Anderson, Leif; Carter-Journet, Katrina; Box, Neil; DiFilippo, Denise; Harrington, Sean; Jackson, David; Lutomski, Michael

    2012-01-01

    This paper introduces an analytical approach, Probability and Confidence Trade-space (PACT), which can be used to assess uncertainty in International Space Station (ISS) hardware sparing necessary to extend the life of the vehicle. There are several key areas under consideration in this research. We investigate what sparing confidence targets may be reasonable to ensure vehicle survivability and for completion of science on the ISS. The results of the analysis will provide a methodological basis for reassessing vehicle subsystem confidence targets. An ongoing annual analysis currently compares the probability of existing spares exceeding the total expected unit demand of the Orbital Replacement Unit (ORU) in functional hierarchies approximating the vehicle subsystems. In cases where the functional hierarchies availability does not meet subsystem confidence targets, the current sparing analysis further identifies which ORUs may require additional spares to extend the life of the ISS. The resulting probability is dependent upon hardware reliability estimates. However, the ISS hardware fleet carries considerable epistemic uncertainty (uncertainty in the knowledge of the true hardware failure rate), which does not currently factor into the annual sparing analysis. The existing confidence targets may be conservative. This paper will also discuss how confidence targets may be relaxed based on the inclusion of epistemic uncertainty for each ORU. The paper will conclude with strengths and limitations for implementing the analytical approach in sustaining the ISS through end of life, 2020 and beyond.

  4. Lipid-based nanosystems for CD44 targeting in cancer treatment: recent significant advances, ongoing challenges and unmet needs.

    Science.gov (United States)

    Nascimento, Thais Leite; Hillaireau, Hervé; Vergnaud, Juliette; Fattal, Elias

    2016-07-01

    Extensive experimental evidence demonstrates the important role of hyaluronic acid (HA)-CD44 interaction in cell proliferation and migration, inflammation and tumor growth. Taking advantage of this interaction, the design of HA-modified nanocarriers has been investigated for targeting CD44-overexpressing cells with the purpose of delivering drugs to cancer or inflammatory cells. The effect of such modification on targeting efficacy is influenced by several factors. In this review, we focus on the impact of HA-modification on the characteristics of lipid-based nanoparticles. We try to understand how these modifications influence particle physicochemical properties, interaction with CD44 receptors, intracellular trafficking pathways, toxicity, complement/macrophage activation and pharmacokinetics. Our aim is to provide insight in tailoring particle modification by HA in order to design more efficient CD44-targeting lipid nanocarriers.

  5. Detailed analysis of targeted gene mutations caused by the Platinum-Fungal TALENs in Aspergillus oryzae RIB40 strain and a ligD disruptant.

    Science.gov (United States)

    Mizutani, Osamu; Arazoe, Takayuki; Toshida, Kenji; Hayashi, Risa; Ohsato, Shuichi; Sakuma, Tetsushi; Yamamoto, Takashi; Kuwata, Shigeru; Yamada, Osamu

    2017-03-01

    Transcription activator-like effector nucleases (TALENs), which can generate DNA double-strand breaks at specific sites in the desired genome locus, have been used in many organisms as a tool for genome editing. In Aspergilli, including Aspergillus oryzae, however, the use of TALENs has not been validated. In this study, we performed genome editing of A. oryzae wild-type strain via error of nonhomologous end-joining (NHEJ) repair by transient expression of high-efficiency Platinum-Fungal TALENs (PtFg TALENs). Targeted mutations were observed as various mutation patterns. In particular, approximately half of the PtFg TALEN-mediated deletion mutants had deletions larger than 1 kb in the TALEN-targeting region. We also conducted PtFg TALEN-based genome editing in A. oryzae ligD disruptant (ΔligD) lacking the ligD gene involved in the final step of the NHEJ repair and found that mutations were still obtained as well as wild-type. In this case, the ratio of the large deletions reduced compared to PtFg TALEN-based genome editing in the wild-type. In conclusion, we demonstrate that PtFg TALENs are sufficiently functional to cause genome editing via error of NHEJ in A. oryzae. In addition, we reveal that genome editing using TALENs in A. oryzae tends to cause large deletions at the target region, which were partly suppressed by deletion of ligD.

  6. Barriers to blood pressure control in African Americans. Overcoming obstacles is challenging, but target goals can be attained.

    Science.gov (United States)

    Douglas, Janice G; Ferdinand, Keith C; Bakris, George L; Sowers, James R

    2002-10-01

    Outdated and biased attitudes and care standards impede optimal care of hypertension in African Americans. The negative expectations that blood pressure targets cannot be reached must be overcome by systematic and appropriate education and treatment. However, physicians should expect that (1) African American patients with elevated blood pressure benefit from early and intensive management, (2) blood pressure can be maintained at goal with appropriate therapeutic lifestyle changes and medications, and (3) complications related to high blood pressure can be avoided. To bring blood pressure down to the target goal, combination pharmacologic therapy is often required. When extensive efforts to achieve blood pressure control prove unattainable in the primary care setting, consultation with a hypertension specialist should be considered.

  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. Stop TB-Halte à la Tuberculose-Canada: engaging industrialised nations in the challenge to meet global targets.

    Science.gov (United States)

    Fanning, A; Billo, N; Tannenbaum, T; Phypers, M; Little, C; Graham, B; Mill, J

    2004-01-01

    The Stop TB Partnership has engaged the 22 high-burden countries in a drive toward the goal of finding 70% of cases and curing 85% by 2005. Traditional partners, aid agencies and governments of industrialised nations have joined the Partnership, but the broader range of civil society remains outside the discourse, risking disinterest on the part of the donor community. Stop TB-Halte à la Tuberculose-Canada was organised to engage new partners to support the Canadian government's commitment to the goal of reducing poverty and diseases of poverty, including tuberculosis, by 50% by 2010. The successes and challenges are explored, and the possibility raised that having a Stop TB movement in every country will ensure that support is sustained and goals of global tuberculosis control reached.

  9. Membrane targeting of MnSOD is essential for oxidative stress tolerance of nitrogen-fixing cultures of Anabaena sp. strain PCC7120.

    Science.gov (United States)

    Raghavan, Prashanth S; Rajaram, Hema; Apte, Shree Kumar

    2015-07-01

    The nitrogen-fixing cyanobacterium, Anabaena PCC7120 encodes for a membrane-targeted 30 kDa Mn-superoxide dismutase (MnSOD) and a cytosolic FeSOD. The MnSOD is post-translationally processed to 27 and 24 kDa forms in the cytosol and periplasm/thylakoid lumen. The extent of cleavage of signal and linker peptides at the N-terminus is dependent on the availability of combined nitrogen during growth. While the 24 and 27 kDa forms are present in near equal proportions under nitrogen-fixing conditions, the 24 kDa form is predominant under nitrogen-supplemented conditions. Individual contribution of these forms of MnSOD to total oxidative stress tolerance was analysed using recombinant Anabaena strains overexpressing either different molecular forms of MnSOD or MnSOD defective in the cleavage of signal/linker peptide. Targeting of MnSOD to the membrane and subsequent cleavage to release both the 24 and 27 kDa forms was essential for oxidative stress tolerance under nitrogen-fixing conditions. On the other hand, the cleavage of linker peptide was absolutely essential and the release of cytosolic 24 kDa form of MnSOD was obligatory for developing oxidative stress tolerance under nitrogen-supplemented conditions. Thus, a single MnSOD caters to the reduction of superoxide radical in both cytosol and thylakoid lumen/periplasm irrespective of the N-status of growth by regulating its cleavage. This is the first report on the physiological advantage of membrane-targeting and processing of MnSOD in either bacteria or plants. The higher oxidative stress tolerance offered by the cytosolic form of MnSOD has possibly resulted in retention of only the cytosolic form in bacterial non-nitrogen-fixers during evolution.

  10. Vaccination-challenge studies with a Port Chalmers/73 (H3N2)-based swine influenza virus vaccine: Reflections on vaccine strain updates and on the vaccine potency test.

    Science.gov (United States)

    De Vleeschauwer, Annebel; Qiu, Yu; Van Reeth, Kristien

    2015-05-11

    The human A/Port Chalmers/1/73 (H3N2) influenza virus strain, the supposed ancestor of European H3N2 swine influenza viruses (SIVs), was used in most commercial SIV vaccines in Europe until recently. If manufacturers want to update vaccine strains, they have to perform laborious intratracheal (IT) challenge experiments and demonstrate reduced virus titres in the lungs of vaccinated pigs. We aimed to examine (a) the ability of a Port Chalmers/73-based commercial vaccine to induce cross-protection against a contemporary European H3N2 SIV and serologic cross-reaction against H3N2 SIVs from Europe and North America and (b) the validity of intranasal (IN) challenge and virus titrations of nasal swabs as alternatives for IT challenge and titrations of lung tissue in vaccine potency tests. Pigs were vaccinated with Suvaxyn Flu(®) and challenged by the IT or IN route with sw/Gent/172/08. Post-vaccination sera were examined in haemagglutination-inhibition assays against vaccine and challenge strains and additional H3N2 SIVs from Europe and North America, including an H3N2 variant virus. Tissues of the respiratory tract and nasal swabs were collected 3 days post challenge (DPCh) and from 0-7 DPCh, respectively, and examined by virus titration. Two vaccinations consistently induced cross-reactive antibodies against European H3N2 SIVs from 1998-2012, but minimal or undetectable antibody titres against North American viruses. Challenge virus titres in the lungs, trachea and nasal mucosa of the vaccinated pigs were significantly reduced after both IT and IN challenge. Yet the reduction of virus titres and nasal shedding was greater after IT challenge. The Port Chalmers/73-based vaccine still offered protection against a European H3N2 SIV isolated 35 years later and with only 86.9% amino acid homology in its HA1, but it is unlikely to protect against H3N2 SIVs that are endemic in North America. We use our data to reflect on vaccine strain updates and on the vaccine potency test.

  11. Transgenic Bt rice does not challenge host preference of the target pest of rice leaffolder, Cnaphalocrocis medinalis (Lepidoptera: Pyralidae.

    Directory of Open Access Journals (Sweden)

    Xiao Sun

    Full Text Available BACKGROUND: Transgenic Bt rice line T2A-1 expresses a synthesized cry2A gene that shows high resistance to Lepidoptera pests, including Cnaphalocrocis medinalis (Guenée (Lepidoptera: Pyralidae. Plant volatile orientation cues and the physical characteristics of the leaf surface play key roles in host location or host-plant acceptance of phytophagous insects. These volatile compounds and physical traits may become altered in Bt rice and it is not known whether this influences the behavior of C. medinalis when searching for oviposition sites. RESULTS: The results of electronic nose analysis showed that the Radar map of Bt rice cultivars was analogous to the non- Bt rice cultivars at each growing stage. PCA analysis was able to partly discriminate between some of the Bt vs. non-Bt rice sensors, but could not to separate Bt cultivars from non-Bt cultivars. The total ion chromatogram between Bt and non-Bt rice cultivars at the seedling, booting and tillering stages were similar and 25 main compounds were identified by GC-MS. For most compounds, there was no significant difference in compound quantities between Bt and non-Bt rice cultivars at equivalent growth stages. The densities of the tubercle papicles and the trichomes on the upper and lower surfaces were statistically equal in Bt and non-Bt rice. The target pest, C. medinalis, was attracted to host rice plants, but it could not distinguish between the transgenic and the isogenic rice lines. CONCLUSIONS: There were no significant differences between the Bt rice line, T2A-1 and the non-Bt rice for volatiles produced or in its physical characteristics and there were no negative impacts on C. medinalis oviposition behavior. These results add to the mounting evidence that Bt rice has no negative impact on the target insect oviposition behavior.

  12. The Liver as a Target Organ for Gene Therapy: State of the Art, Challenges, and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Frank Jacobs

    2012-12-01

    Full Text Available The liver is a target for gene therapy of inborn errors of metabolism, of hemophilia, and of acquired diseases such as liver cancer and hepatitis. The ideal gene transfer strategy should deliver the transgene DNA to parenchymal liver cells with accuracy and precision in the absence of side effects. Liver sinusoids are highly specialized capillaries with a particular endothelial lining: the endothelium contains open fenestrae, whereas a basal lamina is lacking. Fenestrae provide a direct access of gene transfer vectors to the space of Disse, in which numerous microvilli from parenchymal liver cells protrude. The small diameter of fenestrae in humans constitutes an anatomical barrier for most gene transfer vectors with the exception of adeno-associated viral (AAV vectors. Recent studies have demonstrated the superiority of novel AAV serotypes for hepatocyte-directed gene transfer applications based on enhanced transduction, reduced prevalence of neutralizing antibodies, and diminished capsid immune responses. In a landmark clinical trial, hemophilia B was successfully treated with an AAV8 human factor IX expressing vector. Notwithstanding significant progress, clinical experience with these technologies remains very limited and many unanswered questions warrant further study. Therefore, the field should continue to progress as it has over the past decade, cautiously and diligently.

  13. miR-31 Links Lipid Metabolism and Cell Apoptosis in Bacteria-Challenged Apostichopus japonicus via Targeting CTRP9

    Science.gov (United States)

    Shao, Yina; Li, Chenghua; Xu, Wei; Zhang, Pengjuan; Zhang, Weiwei; Zhao, Xuelin

    2017-01-01

    The biological functions of microRNAs (miRNAs) have been studied in a number of eukaryotic species. Recent studies on vertebrate animals have demonstrated critical roles of miRNA in immune and metabolic activities. However, studies on the functions of miRNA in invertebrates are very limited. Here, we demonstrated that miR-31 from Apostichopus japonicus disrupts the balance of lipid metabolism, thus resulting in cell apoptosis by targeting complement C1q tumor necrosis factor-related protein 9 (AjCTRP9), a novel adipokine with pleiotropic functions in immunity and metabolism. Lipidomic analysis suggested that the intercellular lipid metabolites were markedly altered, and three ceramide (Cer) species synchronously increased in the AjCTRP9-silenced coelomocytes. Moreover, exogenous Cer exposure significantly induced apoptosis in the coelomocytes in vivo, in agreement with findings from miR-31 mimic- or AjCTRP9 small-interfering RNA-transfected coelomocytes. Furthermore, we found that the imbalance in sphingolipid metabolism triggered by the overproduction of Cers ultimately resulted in the activation of the apoptosis initiator caspase-8 and executioner caspase-3. Our findings provide the first direct evidence that miR-31 negatively modulates the expression of AjCTRP9 and disturbance of Cer channels, thus leading to caspase-3- and caspase-8-dependent apoptosis, during the interactions between pathogens and host.

  14. Cytopathogenesis of Naegleria fowleri Thai strains for cultured human neuroblastoma cells.

    Science.gov (United States)

    Tiewcharoen, Supathra; Malainual, Nat; Junnu, Virach; Chetanachan, Pruksawan; Rabablert, Jundee

    2008-04-01

    The aim of this study is to evaluate cellular interaction between free-living amoebae Naegleria fowleri strains and mammalian target cells in vitro. Two Thai strains of N. fowleri; Khon Kaen strain from the environment and Siriraj strain from the patient's cerebrospinal fluid and the Center of Disease Control VO 3081 strain from Atlanta (US) were studied. Human neuroblastoma (SK-N-MC) and African Green monkey Kidney (Vero) cells were used as target cells. Each cell line was inoculated with each strain of N. fowleri at a ratio of 1:1 and observed for 7 days. The uninoculated target cells and each strain of N. fowleri were used as control. The numbers of the challenged and unchallenged cells as well as the free-living amoebae were counted three times by trypan blue exclusion method. The inoculation began when the amoebae attached to the cell membrane and ingested the target cells. In this study, extensive cytopathogenesis with many floating inoculated cells and abundant number of amoebae were observed. The destruction pattern of both inoculated SK-N-MC and Vero target cells were similar. Interestingly, SK-N-MC was more susceptible to N. fowleri strains than the Vero cell. In addition, N. fowleri Siriraj strain showed the highest destruction pattern for each target cell. Our findings suggest that the SK-N-MC should be used as a base model for studying the neuropathogenesis in primary amoebic meningoencephalitis patients.

  15. EGFR-targeted drugs for colorectal cancer: current status and future challenges%EGFR靶向药物在结直肠癌中的研究进展

    Institute of Scientific and Technical Information of China (English)

    王丽; 余英豪

    2011-01-01

    Colorectal cancer is a common gastrointestinal malignancy. The effects of traditional chemotherapy and radiation therapy against colorectal cancer are not satisfactory. The epidermal growth factor receptor (EGFR) signaling pathway plays an important role in tumor proliferation, angiogenesis, invasion, and metastasis in colorectal cancer. EGFR-targeted drugs have been developed and applied to the treatment of colorectal cancer. This paper provides a literature review on the current status and future challenges of EGFR-targeted therapy of colorectal cancer.%结直肠癌是常见的消化系恶性肿瘤,传统的化疗和放疗效果均不甚理想.表皮生长因子受体(EGFR)q%号转导通路在结直肠癌细胞的增殖、血管生成、侵袭、转移等方面有重要作用.因此,针对EGFR的靶向药物已陆续开发,并应用于结直肠癌治疗的临床实践.本文就EGFR靶向药物在结直肠癌中的研究现状及其相关问题进行综述.

  16. 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.

  17. Unravelling the genetic bases of non-target-site-based resistance (NTSR) to herbicides: a major challenge for weed science in the forthcoming decade.

    Science.gov (United States)

    Délye, Christophe

    2013-02-01

    Non-target-site-based resistance (NTSR) can confer unpredictable cross-resistance to herbicides. However, the genetic determinants of NTSR remain poorly known. The current, urgent challenge for weed scientists is thus to elucidate the bases of NTSR so that detection tools are developed, the evolution of NTSR is understood, the efficacy of the shrinking herbicide portfolio is maintained and integrated weed management strategies, including fully effective herbicide applications, are designed and implemented. In this paper, the importance of NTSR in resistance to herbicides is underlined. The most likely way in which NTSR evolves-by accumulation of different mechanisms within individual plants-is described. The NTSR mechanisms, which can interfere with herbicide penetration, translocation and accumulation at the target site, and/or protect the plant against the consequences of herbicide action, are then reviewed. NTSR is a part of the plant stress response. As such, NTSR is a dynamic process unrolling over time that involves 'protectors' directly interfering with herbicide action, and also regulators controlling 'protector' expression. NTSR is thus a quantitative trait. On this basis, a three-step procedure is proposed, based on the use of the 'omics' (genomics, transcriptomics, proteomics or metabolomics), to unravel the genetic bases of NTSR.

  18. 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

  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

    2016-03-01

    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.

  20. 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

  1. 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.

    Science.gov (United States)

    Nol, Pauline; Olsen, Steven C; Rhyan, Jack C; Sriranganathan, Nammalwar; McCollum, Matthew P; Hennager, Steven G; Pavuk, Alana A; Sprino, Phillip J; Boyle, Stephen M; Berrier, Randall J; Salman, Mo D

    2016-01-01

    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 glycosyltransferase 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.

  2. 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....

  3. 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...

  4. 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...

  5. Deuteron irradiation of W and WO3 for production of high specific activity (186)Re: Challenges associated with thick target preparation.

    Science.gov (United States)

    Balkin, Ethan R; Gagnon, Katherine; Strong, Kevin T; Smith, Bennett E; Dorman, Eric F; Emery, Robert C; Pauzauskie, Peter J; Fassbender, Michael E; Cutler, Cathy S; Ketring, Alan R; Jurisson, Silvia S; Wilbur, D Scott

    2016-09-01

    This investigation evaluated target fabrication and beam parameters for scale-up production of high specific activity (186)Re using deuteron irradiation of enriched (186)W via the (186)W(d,2n)(186)Re reaction. Thick W and WO3 targets were prepared, characterized and evaluated in deuteron irradiations. Full-thickness targets, as determined using SRIM, were prepared by uniaxially pressing powdered natural abundance W and WO3, or 96.86% enriched (186)W, into Al target supports. Alternatively, thick targets were prepared by pressing (186)W between two layers of graphite powder or by placing pre-sintered (1105°C, 12h) natural abundance WO3 pellets into an Al target support. Assessments of structural integrity were made on each target prepared. Prior to irradiation, material composition analyses were conducted using SEM, XRD, and Raman spectroscopy. Within a minimum of 24h post irradiation, gamma-ray spectroscopy was performed on all targets to assess production yields and radionuclidic byproducts. Problems were encountered with the structural integrity of some pressed W and WO3 pellets before and during irradiation, and target material characterization results could be correlated with the structural integrity of the pressed target pellets. Under the conditions studied, the findings suggest that all WO3 targets prepared and studied were unacceptable. By contrast, (186)W metal was found to be a viable target material for (186)Re production. Thick targets prepared with powdered (186)W pressed between layers of graphite provided a particularly robust target configuration.

  6. Screening and confirming of target strains from the faeces of rats fed with lactobacilli strains feed to SD rat%乳杆菌喂食大鼠后目标菌克隆筛选与确认

    Institute of Scientific and Technical Information of China (English)

    何琼伟; 陶祝华; 朱一力; 郑刚; 李伟莉; 林蓉; 金嵘; 陈龙; 曾爱兵

    2011-01-01

    目的 确认乳杆菌能否顺利通过胃酸屏障并在肠道内定植为进一步研究乳杆菌对大鼠的生理代谢影响做基础,为乳杆菌菌株的应用提供有效依据.方法 采用浓度梯度药物平板筛选利福平耐受菌株,用耐利福平(15 mg/L)乳杆菌菌株喂食SD雄性大鼠并采集其新鲜粪便,在耐药平板上筛选出能在大鼠结肠内定植良好的耐药菌株,并得到16S rDNA的鉴定结果,利用16S rDNA序列同源性分析对乳酸菌进行分类鉴定.结果 粪便中检测出的乳杆菌耐药菌株经纯化鉴定后与所喂食的乳杆菌同源.结论 实验所筛选出的耐利福平乳杆菌在大鼠结肠内成功定植.%Objective To confirm whether lactobacilli could overcome the gastric acid barrier and localize in the intestines of rats, so to provide basis for further studies on the effect of lactobacilli's localization on rats' physiological characteristics and for the application of the strains. Method Plates with grediant concentration of rifampicin were used to screen the resistant strains. Rifampicin-resistant lactobacilli ( > 15 μg/mL) were fed to SD and then the fresh faeces of the SD male rats were collected. The strains which could localize in rats' colons well were then genetically identified with 16S rDNA sequence analysis. Result After purification, the lactobacilli resistant strains detected from the male rats' faeces were identified as homologous to the fed ones. Conclusion The lactobacifius strains screened in this study can localize stably in rat's colon.

  7. Preliminary results of sero-conversion of kids and lambs vaccinated with Brucella melitensis rev -1 strain. Current achievements and feature challenges on brucellosis

    Directory of Open Access Journals (Sweden)

    XHELIL KOLECI

    2014-06-01

    Full Text Available Sheep and goat brucellosis is an endemic and most important infectious disease of livestock in Albania. It continues to remain a frequent zoonotic disease and an important public health issue. Among available strategies, mass vaccination is an acceptable, cost effective approach, and is a widely used strategy in many countries including some neighbouring Balkan countries. Albanian veterinary services supported by the European Union-funded PAZA project (Protection Against Zoonotic diseases, Albania applied two successive annual mass vaccination campaigns that aimed to vaccinate all small ruminants in the country. These two campaigns aimed at significantly reducing disease spread, however, a small number of infection foci could remain and persist in some parts of country. Post-vaccination surveillance is essential for early detection and proper control of cases of brucellosis that might re-emerge. Limitation major complication arising from mass vaccination is the difficulty of interpretation of the results of serological tests conducted to diagnose the disease. The aim of this study was to evaluate the proportion of vaccinated animals that showed sero-conversion and the duration of detectable levels of agglutinins (antibody against brucellosis in vaccinated animals. Methods. In total, 69 individual animals, 23 lambs and 46 kids aged from 4 to 7 months, were sampled at monthly intervals. Jugular blood was collected before vaccination and at intervals thereafter and tested by means of the Rose Bengal test. All animals were serologically negative before vaccination with modified live Brucella melitensis Rev.1 strain vaccine. Rose Bengal test was performed before vaccination, 18 days, 2, 3 and 4 months after vaccination. Results. Eighteen days after vaccination, 63 out of 69 animals (91.3% 82.6% of lambs (19 out of 23 lambs and 95.6% of goat kids (44 out of 46 showed strong sero-conversion in Rose Bengal test. The proportion of positive vaccinated

  8. 鸭肠炎病毒强毒参考株在感染鸭体内的动态分布研究%Dynamic Distribution of Duck Enteritis Virus Standard Challenge Strain in Experimentally Infected Ducklings

    Institute of Scientific and Technical Information of China (English)

    文晶亮; 李俊平; 李启红; 李岭; 孙淼; 李慧姣; 杨承槐; 夏业才

    2014-01-01

    为研究鸭肠炎病毒( DEV)强毒株在感染鸭体内的动态分布规律,根据DEV的gD基因序列设计检测引物RT-gDF和RT-gDR,建立了特异性强、敏感性高、重复性好的检测DEV的SYBR GreenⅠ实时荧光定量PCR方法。应用已建立的方法,对DEV强毒参考株感染鸭的组织脏器进行了定量检测。结果显示,接种后6 h即可在所有受检组织中检测到DEV DNA,随着病程发展, DNA拷贝数持续升高,直至接种5 d后感染鸭全部死亡。其中结肠病毒DNA拷贝数为最高,达到1013.26 copies/g,法氏囊、肝脏和盲肠次之,约1012 copies/g。证实了DEV强毒对感染鸭的免疫器官、神经组织和消化系统均具有广泛的嗜性。%To explore the dynamic distribution of duck enteritis virus challenge standard strain ( DEV CSC ) in experimentally infected ducklings, the specific primers ( RT-gDF and RT-gDR) were designed according to the gene DEV gD, and the SYBR GreenⅠreal-time fluorescent quantitative PCR method for virulent strain with satisfaction of specificity, sensibility and repeatability was established. Copies of DEV DNA were quantified in the collected tissues by the fluorescent quantitative PCR method. In result, DEV CSC DNA were firstly detected in all the samples at six hours after inoculation and the DNA copies subsequently continued to rise till the death of all the ducklings infected with DEV CSC virulent strain five days after inoculation. The DNA copies of DEV CSC strain in colon(1013.26 copies/g) of dead ducklings was highest, and then came to bursa of Fabricius, caecum and liver, about 1012 copies/g. The results above comfirmed that the virulent strain CSC had broad tissue tropism on immune organs, nerve tissue and digestive system of infected ducks.

  9. DNA-Based diagnostic tests for Salmonella strains targeting hilA, agfA, spvC and sef Genes

    Energy Technology Data Exchange (ETDEWEB)

    Craciunafl, C.; Keul, A. L.; Flonta, M.; Cristea, M.

    2009-07-01

    Salmoneleae are invasive enteropathogens of humans and animals. During the past decade, a dramatic increase in the occurrence of Salmonella spp infections was principally responsible for the rise of food-borne salmonellosis. The goal of this study was to evaluate the suitability of the, hilA, agfA, spvC, sef, gene amplification by PCR as a specific method for detection of Salmonella strains. (Author)

  10. HCV Drug Resistance Challenges in Japan: The Role of Pre-Existing Variants and Emerging Resistant Strains in Direct Acting Antiviral Therapy

    Directory of Open Access Journals (Sweden)

    Kazuaki Chayama

    2015-10-01

    Full Text Available Sustained virological response (SVR rates have increased dramatically following the approval of direct acting antiviral (DAA therapies. While individual DAAs have a low barrier to resistance, most patients can be successfully treated using DAA combination therapy. However, DAAs are vulnerable to drug resistance, and resistance-associated variants (RAVs may occur naturally prior to DAA therapy or may emerge following drug exposure. While most RAVs are quickly lost in the absence of DAAs, compensatory mutations may reinforce fitness. However, the presence of RAVs does not necessarily preclude successful treatment. Although developments in hepatitis C virus (HCV therapy in Asia have largely paralleled those in the United States, Japan’s July 2014 approval of asunaprevir plus daclatasvir combination therapy as the first all-oral interferon-free therapy was not repeated in the United States. Instead, two different combination therapies were approved: sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir/dasabuvir. This divergence in treatment approaches may lead to differences in resistance challenges faced by Japan and the US. However, the recent approval of sofosbuvir plus ledipasvir in Japan and the recent submissions of petitions for approval of paritaprevir/ritonavir plus ombitasvir suggest a trend towards a new consensus on emerging DAA regimens.

  11. 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

    acids, while maintaining sufficiently high growth rate and minimizing the secretion of undesired byproducts. Homo-productions of acetic, lactic and succinic acids were targeted as examples. Engineered E. coli strains capable of producing homo-acetic and homo-lactic acids could be developed by taking...... this systems approach for the minimal identification of gene knockout targets. Also, failure to predict effective gene knockout targets for the homo-succinic acid production suggests that the multi-objective optimization is useful in assessing the suitability of a microorganism as a host strain......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...

  12. Investigation into the Combined Effects of Compaction, Strain Rate Sensitivity, and Anisotropic Damage of a Geologic Target on the Trajectory Stability of Rigid Penetrators

    Science.gov (United States)

    2007-05-01

    associated to the loss of cohesive strength due to air pore collapse. Following Holmquist et al. (1993), we consider that the shear flow stress is of the...0.6 / 300 0I I ~ OMO ~200 0.2 0* 01 UJ 100 0 0.05 0.1volumetric strain 0I I 0 200 400 600 800 1000 MPa compressive pressure -p Figure 7: Left: the...taken into account while the damage pa- rameter is associated to the loss of cohesive strength due to air pore collapse. For hydrostatic conditions, the

  13. Amplicon based RNA interference targeting V2 gene of cotton leaf curl Kokhran virus-Burewala strain can provide resistance in transgenic cotton plants

    Science.gov (United States)

    An RNAi based gene construct designated “C2” was used to target the V2 region of the cotton leaf curl virus (CLCuV) genome which is responsible for virus movement. The construct was transformed into two elite cotton varieties MNH-786 and VH-289. A shoot apex method of plant transformation using Agr...

  14. 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

    2014-02-01

    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, more than 100 structures were suggested as prediction targets, some of which appeared to be extraordinarily difficult for modeling. In this article, 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 transmembrane 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 fiber protein gene product 17 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.

  15. 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

  16. Workshop targets development of geodetic transient detection methods: 2009 SCEC Annual Meeting: Workshop on transient anomalous strain detection; Palm Springs, California, 12-13 September 2009

    Science.gov (United States)

    Murray-Moraleda, Jessica R.; Lohman, Rowena

    2010-01-01

    The Southern California Earthquake Center (SCEC) is a community of researchers at institutions worldwide working to improve understanding of earthquakes and mitigate earthquake risk. One of SCEC's priority objectives is to “develop a geodetic network processing system that will detect anomalous strain transients.” Given the growing number of continuously recording geodetic networks consisting of hundreds of stations, an automated means for systematically searching data for transient signals, especially in near real time, is critical for network operations, hazard monitoring, and event response. The SCEC Transient Detection Test Exercise began in 2008 to foster an active community of researchers working on this problem, explore promising methods, and combine effective approaches in novel ways. A workshop was held in California to assess what has been learned thus far and discuss areas of focus as the project moves forward.

  17. Strategies to develop strain-specific PCR based assays for probiotics.

    Science.gov (United States)

    Treven, P

    2015-01-01

    Since health benefits conferred by probiotics are strain-specific, identification to the strain level is mandatory to allow the monitoring of the presence and the abundance of specific probiotic in a product or in a gastrointestinal tract. Compared to standard plate counts, the reduced duration of the assays and higher specificity makes PCR-based methods (standard PCR and quantitative PCR) very appropriate for detection or quantification of probiotics. Development of strain-specific assay consists of 4 main stages: (1) strain-specific marker identification; (2) construction of potential strain-specific primers; (3) validation on DNA from pure cultures of target and related strains; and (4) validation on spiked samples. The most important and also the most challenging step is the identification of strain-specific sequences, which can be subsequently targeted by specific primers or probes. Such regions can be identified on sequences derived from 16S-23S internally transcribed spacers, randomly amplified polymorphic DNA, representational difference analysis and suppression subtractive hybridisation. Already known phenotypic or genotypic characteristics of the target strain can also be used to develop the strain-specific assay. However, the initial stage of strain-specific assay development can be replaced by comparative genomics analysis of target genome with related genomes in public databases. Advances in whole genome sequencing (WGS) have resulted in a cost reduction for bacterial genome sequencing and consequently have made this approach available to most laboratories. In the present paper I reviewed the available literature on PCR and qPCR assays developed for detection of a specific probiotic strain and discussed future WGS and comparative genomics-based approaches.

  18. 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…

  19. 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.

  20. Role of the North Sea power transmission in realising the 2020 renewable energy targets. Planning and permitting challenges: a deliverable from WP 4 regulatory framework

    Energy Technology Data Exchange (ETDEWEB)

    Kielland, Jens Jacob; Ruud, Audun

    2012-07-01

    This study explores and assesses challenges for the European permitting and planning system with regard to grid development in the North Sea. The following question is discussed: What planning and permitting challenges can influence the realization of an offshore grid in the North Sea? This is answered by referring to the political context of the North Sea and the development of an offshore grid therein. We present the main features of the proposed regulation by the European Commission (COM(2011)658) that will, if it is adapted, impact current grid permitting procedures. Further, key supranational planning tools for offshore grid development are accounted for and the proposed EU measures are discussed with reference to relevant studies on planning and permitting procedures of realizing electricity grids. Finally, the report provides the general findings and conclusions. (Author)

  1. A strain-based porosity model for use in hydrocode simulations of impacts and implications for transient crater growth in porous targets

    Science.gov (United States)

    Wünnemann, K.; Collins, G. S.; Melosh, H. J.

    2006-02-01

    Numerical modelling of impact cratering has reached a high degree of sophistication; however, the treatment of porous materials still poses a large problem in hydrocode calculations. We present a novel approach for dealing with porous compaction in numerical modelling of impact crater formation. In contrast to previous attempts (e.g., P-alpha model, snowplow model), our model accounts for the collapse of pore space by assuming that the compaction function depends upon volumetric strain rather than pressure. Our new ɛ-alpha model requires only four input parameters and each has a physical meaning. The model is simple and intuitive and shows good agreement with a wide variety of experimental data, ranging from static compaction tests to highly dynamic impact experiments. Our major objective in developing the model is to investigate the effect of porosity and internal friction on transient crater formation. We present preliminary numerical model results that suggest that both porosity and internal friction play an important role in limiting crater growth over a large range in gravity-scaled source size.

  2. 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.

  3. 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

  4. Where to Target Conservation Agriculture for African Smallholders? How to Overcome Challenges Associated with its Implementation? Experience from Eastern and Southern Africa

    Directory of Open Access Journals (Sweden)

    Frédéric Baudron

    2015-07-01

    Full Text Available Since the paper by Giller et al. (2009, the debate surrounding the suitability of conservation agriculture (CA for African smallholders has remained polarized between proponents and opponents. The debate also gave rise to a few studies that attempted to identify the “niche” where CA would fit in the region, but the insight offered by these studies has been limited. In this paper, we first analyze the rationale of adoption where it occurred globally to define “drivers” of adoption. Our analysis suggests that CA has first and foremost been adopted under the premises of being energy-saving (time and/or power, erosion-controlling, and water-use efficient, but rarely to increase yield. We then define the niche where CA fits, based on these drivers of adoption, as systems where (1 the energy available for crop establishment is limited and/or costly (including labor and draft power; (2 delayed planting results in a significant yield decline; (3 yield is limited or co-limited by water; and/or (4 severe erosion problems threaten the short- to medium-term productivity of farmland. In Eastern and Southern Africa, this niche appears rather large and likely to expand in the near future. When implemented within this niche, CA may still be limited by “performance challenges” that do not constitute drivers or barriers to adoption, but limitations to the performance of CA. We argue that most of these performance challenges can (and should be addressed by agronomic and socio-economic research, and provide four examples where the International Maize and Wheat Improvement Center (CIMMYT and its partners have been successfully alleviating four very different challenges through research and development (R&D in Eastern and Southern Africa. Finally, we describe an iterative and multi-scale R&D approach currently used by CIMMYT in Eastern and Southern Africa to overcome challenges associated with the implementation of CA by African smallholders. This

  5. Tackling the climate targets set by the Paris Agreement (COP 21: Green leadership empowers public hospitals to overcome obstacles and challenges in a resource-constrained environment

    Directory of Open Access Journals (Sweden)

    E Weimann

    2017-01-01

    Full Text Available The healthcare sector itself contributes to climate change, the creation of hazardous waste, use of toxic metals such as mercury, and water and air pollution. To mitigate the effect of healthcare provision on the deteriorating environment and avoid creating further challenges for already burdened health systems, Global Green Hospitals was formed as a global network. Groote Schuur Hospital (GSH, as the leading academic hospital in Africa, joined the network in 2014. Since then, several projects have been initiated to reduce the amount of general waste, energy consumption and food waste, and create an environmentally friendlier and more sustainable hospital in a resource-constrained public healthcare setting. We outline the various efforts made to reduce the carbon footprint of GSH and reduce waste and hazardous substances such as mercury and polystyrene, and elaborate how obstacles and resistance to change were overcome. The hospital was able to halve the amount of coal and water used, increase recycling by 50% over 6 months, replace polystyrene cups and packaging with Forest Stewardship Council recyclable paper-based products, reduce the effect of food wastage by making use of local farmers, and implement measures to reduce the amount of expired pharmaceutical drugs. To improve commitment from all involved roleplayers, political leadership, supportive government policies and financial funding is mandatory, or public hospitals will be unable to tackle the exponentially increasing costs related to climate change and its effects on healthcare.

  6. Tackling the climate targets set by the Paris Agreement (COP 21): Green leadership empowers public hospitals to overcome obstacles and challenges in a resource-constrained environment.

    Science.gov (United States)

    Weimann, E; Patel, B

    2016-12-21

    The healthcare sector itself contributes to climate change, the creation of hazardous waste, use of toxic metals such as mercury, and water and air pollution. To mitigate the effect of healthcare provision on the deteriorating environment and avoid creating further challenges for already burdened health systems, Global Green Hospitals was formed as a global network. Groote Schuur Hospital (GSH), as the leading academic hospital in Africa, joined the network in 2014. Since then, several projects have been initiated to reduce the amount of general waste, energy consumption and food waste, and create an environmentally friendlier and more sustainable hospital in a resource-constrained public healthcare setting. We outline the various efforts made to reduce the carbon footprint of GSH and reduce waste and hazardous substances such as mercury and polystyrene, and elaborate how obstacles and resistance to change were overcome. The hospital was able to halve the amount of coal and water used, increase recycling by 50% over 6 months, replace polystyrene cups and packaging with Forest Stewardship Council recyclable paper-based products, reduce the effect of food wastage by making use of local farmers, and implement measures to reduce the amount of expired pharmaceutical drugs. To improve commitment from all involved roleplayers, political leadership, supportive government policies and financial funding is mandatory, or public hospitals will be unable to tackle the exponentially increasing costs related to climate change and its effects on healthcare.

  7. N-terminal processing of membrane-targeted MnSOD and formation of multiple active superoxide dismutase dimers in the nitrogen-fixing cyanobacterium Anabaena sp. strain PCC7120.

    Science.gov (United States)

    Raghavan, Prashanth S; Rajaram, Hema; Apte, Shree K

    2013-10-01

    Anabaena sp. strain PCC7120 expresses a 30 kDa manganese-dependent superoxide dismutase (MnSOD) comprising a hydrophobic region (signal peptide + linker peptide) attached to a catalytic unit. Bioinformatics predicted cleavage of the signal peptide at (25)CQPQ by signal peptidase and of the linker peptide by an Arg-C-like protease at the Arg52/Arg59 residue. The three predicted forms of MnSOD were immunodetected in Anabaena, with the 30 kDa MnSOD found exclusively in the membrane and the shorter 27 and 24 kDa forms found both in the membrane and soluble fractions. The corresponding sodA gene was truncated for (a) the first eight residues, or, (b) the signal peptide, or (c) the entire hydrophobic region, or (d) the Arg52/Arg59 residues were modified to serine. Overexpression of these MnSOD variants in recombinant Anabaena strains revealed that (a) the 30 kDa membrane-targeted MnSOD was cleaved by membrane-localized signal peptidase either during or after its transport through the membrane to release the 27 kDa form, either in the cytosol or in the periplasmic/thylakoid lumen, (b) the 27 kDa form was further cleaved to the 24 kDa form by Arg-C-like protease, both in the cytosol and in the periplasmic/thylakoid lumen, (c) deletion of signal peptide localized the MnSOD forms in the cytosol, and (d) alteration of the signal/linker peptide cleavage sites interfered with MnSOD localization and processing. Homo/heterodimerization of the 24 and 27 kDa forms of MnSOD and the cytosolic iron-dependent SOD results in multiple SOD activities, from a single MnSOD gene (sodA), in different cellular compartments of Anabaena.

  8. 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.

  9. Optimized E. coli expression strain LOBSTR eliminates common contaminants from His-tag purification.

    Science.gov (United States)

    Andersen, Kasper R; Leksa, Nina C; Schwartz, Thomas U

    2013-11-01

    His-tag affinity purification is one of the most commonly used methods to purify recombinant proteins expressed in E. coli. One drawback of using the His-tag is the co-purification of contaminating histidine-rich E. coli proteins. We engineered a new E. coli expression strain, LOBSTR (low background strain), which eliminates the most abundant contaminants. LOBSTR is derived from the E. coli BL21(DE3) strain and carries genomically modified copies of arnA and slyD, whose protein products exhibit reduced affinities to Ni and Co resins, resulting in a much higher purity of the target protein. The use of LOBSTR enables the pursuit of challenging low-expressing protein targets by reducing background contamination with no additional purification steps, materials, or costs, and thus pushes the limits of standard His-tag purifications.

  10. 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.

  11. 靶向生物制剂在银屑病治疗中的应用现状与挑战%Application status and challenges of targeted biological agents in the treatment of psoriasis

    Institute of Scientific and Technical Information of China (English)

    王虹; 李珊山

    2015-01-01

    There are 6 types of targeted biological agents that have been approved for the treatment of psoriasis by the United States Food and Drug Administration (FDA) including Alefacept,Efalizumab,Infliximab,Adalimumab,Etanercept and Ustekinumab. This paper outlines their structure ,mechanism of action ,clinical efficacy and application status in the treatment of psoriasis .The paper further describes that the targeted biological therapy may also bring a series of adverse reactions and risks by interfering with immune homeostasis when they play a good effect in the treatment of the disease .We also described how to manage these risks .Targeted biologi-cal agents provide a new approach for the treatment of psoriasis ,but make us face a challenge .Their long-term efficacy and safety still needs to be fully verified in clinic .%美国FDA已批准用于银屑病治疗的靶向生物制剂有6种,包括:阿法西普、依法利珠单抗、英夫利昔单抗、阿达木单抗、依那西普、乌斯奴单抗。本文概述了该6种生物制剂的结构、作用机制、在银屑病治疗中的临床疗效及应用现状。阐述了靶向治疗在发挥良好疗效的同时由于干扰了免疫稳态,可能引起的不良反应与治疗风险及其风险管理。靶向生物制剂为银屑病治疗提供了新途径,同时也面临挑战,长期疗效及安全性尚需更充分的临床验证。

  12. The Shigella human challenge model.

    Science.gov (United States)

    Porter, C K; Thura, N; Ranallo, R T; Riddle, M S

    2013-02-01

    Shigella is an important bacterial cause of infectious diarrhoea globally. The Shigella human challenge model has been used since 1946 for a variety of objectives including understanding disease pathogenesis, human immune responses and allowing for an early assessment of vaccine efficacy. A systematic review of the literature regarding experimental shigellosis in human subjects was conducted. Summative estimates were calculated by strain and dose. While a total of 19 studies evaluating nine strains at doses ranging from 10 to 1 × 1010 colony-forming units were identified, most studies utilized the S. sonnei strain 53G and the S. flexneri strain 2457T. Inoculum solution and pre-inoculation buffering has varied over time although diarrhoea attack rates do not appear to increase above 75-80%, and dysentery rates remain fairly constant, highlighting the need for additional dose-ranging studies. Expansion of the model to include additional strains from different serotypes will elucidate serotype and strain-specific outcome variability.

  13. Immunoprophylaxis and immunotherapy of Staphylococcus epidermidis infections: challenges and prospects.

    Science.gov (United States)

    Van Mellaert, Lieve; Shahrooei, Mohammad; Hofmans, Dorien; Eldere, Johan Van

    2012-03-01

    Previously considered a human commensal, Staphylococcus epidermidis is a frequent cause of nosocomial infections and the most common cause of device-related infections. Because the expression of toxins and other obvious virulence factors is less in S. epidermidis, the biofilm-forming capacity is its major virulence factor. Biofilm growth is characterized by high resistance to antimicrobial agents and host immune responses, making biofilm eradication tremendously difficult. The increasing prevalence of multidrug-resistant S. epidermidis strains additionally hampers antimicrobial therapy. Therefore, immunoprophylaxis and immunotherapy targeting factors expressed at some point in biofilm formation might offer new tools to combat S. epidermidis infections. So far, a limited number of targets have been examined for their immunotherapeutic potential. In this review, we focus on the already tested and possible targets for vaccine development, discuss the accompanying challenges and speculate on future possibilities with respect to immunotherapeutic solutions to deal with S. epidermidis infections.

  14. Targets, models and challenges in osteoarthritis research

    Directory of Open Access Journals (Sweden)

    Sarah Thysen

    2015-01-01

    Full Text Available Osteoarthritis is a chronic degenerative disorder of the joint and represents one of the most common diseases worldwide. Its prevalence and severity are increasing owing to aging of the population, but treatment options remain largely limited to painkillers and anti-inflammatory drugs, which only provide symptomatic relief. In the late stages of the disease, surgical interventions are often necessary to partially restore joint function. Although the focus of osteoarthritis research has been originally on the articular cartilage, novel findings are now pointing to osteoarthritis as a disease of the whole joint, in which failure of different joint components can occur. In this Review, we summarize recent progress in the field, including data from novel ‘omics’ technologies and from a number of preclinical and clinical trials. We describe different in vitro and in vivo systems that can be used to study molecules, pathways and cells that are involved in osteoarthritis. We illustrate that a comprehensive and multisystem approach is necessary to understand the complexity and heterogeneity of the disease and to better guide the development of novel therapeutic strategies for osteoarthritis.

  15. Targets, models and challenges in osteoarthritis research.

    Science.gov (United States)

    Thysen, Sarah; Luyten, Frank P; Lories, Rik J U

    2015-01-01

    Osteoarthritis is a chronic degenerative disorder of the joint and represents one of the most common diseases worldwide. Its prevalence and severity are increasing owing to aging of the population, but treatment options remain largely limited to painkillers and anti-inflammatory drugs, which only provide symptomatic relief. In the late stages of the disease, surgical interventions are often necessary to partially restore joint function. Although the focus of osteoarthritis research has been originally on the articular cartilage, novel findings are now pointing to osteoarthritis as a disease of the whole joint, in which failure of different joint components can occur. In this Review, we summarize recent progress in the field, including data from novel 'omics' technologies and from a number of preclinical and clinical trials. We describe different in vitro and in vivo systems that can be used to study molecules, pathways and cells that are involved in osteoarthritis. We illustrate that a comprehensive and multisystem approach is necessary to understand the complexity and heterogeneity of the disease and to better guide the development of novel therapeutic strategies for osteoarthritis.

  16. 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

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

    Science.gov (United States)

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

    2012-03-15

    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 optimised solid-state straw culture conditions, experiments were conducted that compared fungal strains in terms of their growth, enzyme activities (cellulases, xylanase and alcohol dehydrogenase) and yield of bioethanol and the undesirable by-products acetic acid and xylitol. Significant inter-strain divergence was recorded in regards to the capacity of studied F. oxysporum strains to produce alcohol from untreated straw. No correlation was observed between bioethanol synthesis and either the biomass production or microbial enzyme activity. A strong correlation was observed between both acetic acid and xylitol production and bioethanol yield. The level of diversity recorded in the alcohol production capacity among closely-related microorganism means that a targeted screening of populations of selected microbial species could greatly improve bioprocessing yields, in terms of providing both new host strains and candidate genes for the bioethanol industry.

  18. Effect of dietary addition of thymol 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)

    P. Bosi

    2010-04-01

    Full Text Available 64 weaned pigs (24d-old, were fed a control diet or a control plus 1% thymol diet, with or without Salmonella typhimurium challenge. Thymol reduced feed intake but did not affect significantly the final body weight after 29d of trial. Salmonella did not affect the performances. Body temperature was lower in the thymol group before, but also 1d after challenge, when Salmonella increased the values more in unsupplemented pigs. Fecal excretion of S. typhimurium in challenged pigs was not changed by the diet. The thymol group had a higher concentration of immunoglobulin (Ig in serum before the challenge, but after there was an interaction between diet and challenge. The diet and the challenge did not affect saliva parameters, and ATPase gene expression in the fundic gastric mucosa. Thymol increased the number of parietal cells for 100 μm depth of oxintic gland. In conclusion the important supplementation with thymol reduced the intake, but not performance in the medium period. Some factors of the gut barrier were positively influenced. Salmonella challenge did not reduce significantly the performance of the weaned piglet.

  19. 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.

  20. Snowball: Strain aware gene assembly of Metagenomes

    NARCIS (Netherlands)

    Gregor, I.; Schönhuth, A.; McHardy, A.C.

    2015-01-01

    Gene assembly is an important step in functional analysis of shotgun metagenomic data. Nonetheless, strain aware assembly remains a challenging task, as current assembly tools often fail to distinguish among strain variants or require closely related reference genomes of the studied species to be av

  1. Snowball: Strain aware gene assembly of Metagenomes

    OpenAIRE

    Gregor, I.; Schönhuth, A.; McHardy, A. C.

    2015-01-01

    Gene assembly is an important step in functional analysis of shotgun metagenomic data. Nonetheless, strain aware assembly remains a challenging task, as current assembly tools often fail to distinguish among strain variants or require closely related reference genomes of the studied species to be available. We have developed Snowball, a novel strain aware and reference-free gene assembler for shotgun metagenomic data. It uses profile hidden Markov models (HMMs) of gene domains of interest to ...

  2. 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.

  3. Polyhydroxyalkanoates, challenges and opportunities.

    Science.gov (United States)

    Wang, Ying; Yin, Jin; Chen, Guo-Qiang

    2014-12-01

    Microbial polyhydroxyalkanoates (PHA) have been developed as biodegradable plastics for the past many years. However, PHA still have only a very limited market. Because of the availability of large amount of shale gas, petroleum will not raise dramatically in price, this situation makes PHA less competitive compared with low cost petroleum based plastics. Therefore, two strategies have been adopted to meet this challenge: first, the development of a super PHA production strain combined with advanced fermentation processes to produce PHA at a low cost; second, the construction of functional PHA production strains with technology to control the precise structures of PHA molecules, this will allow the resulting PHA with high value added applications. The recent systems and synthetic biology approaches allow the above two strategies to be implemented. In the not so distant future, the new technology will allow PHA to be produced with a competitive price compared with petroleum-based plastics.

  4. 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.

  5. 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.

  6. Synthetic biology of cyanobacteria: unique challenges and opportunities.

    Science.gov (United States)

    Berla, Bertram M; Saha, Rajib; Immethun, Cheryl M; Maranas, Costas D; Moon, Tae Seok; Pakrasi, Himadri B

    2013-01-01

    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.

  7. 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。

  8. Novel opportunities for next-generation probiotics targeting metabolic syndrome.

    Science.gov (United States)

    Cani, Patrice D; Van Hul, Matthias

    2015-04-01

    Various studies have described the beneficial effects of specific bacteria on the characteristics of metabolic syndrome. Intestinal microbiota might therefore represent a modifiable trait for translational intervention to improve the metabolic profiles of obese and type 2 diabetic patients. However, identifying potential probiotic strains that can effectively colonize the gastrointestinal tract and significantly affect host metabolism has been challenging. This review aims to summarize the notable advances and contributions in the field that may prove useful for identifying next-generation probiotics that target metabolic syndrome and its related disorders.

  9. Challenged Pragmatism

    DEFF Research Database (Denmark)

    Christoffersen, Lisbet; Vinding, Niels Valdemar

    2013-01-01

    of religious faith have made religious claims and thereby challenged a secular understanding of the Danish labour market. This raises the question of the extent to which the religion of the individual can be accepted in the general public sphere. At the same time, religious ethos organisations have argued...

  10. Detection of a New Strain of Wolbachia Pipientis in Phlebotomus Perfiliewi Transcaucasicus, a Potential Vector of Visceral Leishmaniasis in North West of Iran, by Targeting the Major Surface Protein Gene

    Directory of Open Access Journals (Sweden)

    Somaieh Soleimani

    2013-03-01

    Full Text Available Background: Wolbachia pipientis is maternally inherited endoparasitic bacterium belonging to the α-proteobacteria, infecting 20–75% of all insect species including sand flies. The Wolbachia surface protein (wsp was employed as an appropriate marker for strain typing. The objective of our research was to find the possibility of detection of W. pipientis in Phlebotomus perfiliewi transcaucasicus.Methods: Individual sand flies were screened for the presence of W. pipientis. The obtained sequences were edited and aligned with database sequences to identify W. pipientis haplotypes.Results: Two haplotypes of W. pipientis were found in P. perfiliewi transcaucasicus. The common haplotype of W. pipientis was found to be identical to the sequences of those submitted in GenBank. New strain (haplotype of W. pipientis was found novel. The sequence of new strain of W. pipientis occurs in P. perfiliewi transcaucasicus is very different from those already submitted in GenBank.Conclusion: Finding one genetically modified new strain of W. pipientis in P. perfiliewi transcaucasicus, now we can conclude that further documents and studies need to reach the role of cytoplasmic incompatibility of W. pipientis through wild sand fly populations to drive a deleterious gene into and to reduce the density of natural populations of sand flies

  11. Target Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — [Part of the ATLAS user facility.] The Physics Division operates a target development laboratory that produces targets and foils of various thickness and substrates,...

  12. 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.

  13. 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.

  14. 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...

  15. 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.

  16. Bernoulli's Challenge

    Science.gov (United States)

    Bouffard, Karen

    1999-01-01

    This month's Olympic activity was brought to the Eastern Massachusetts Physics Olympics group by Ron DeFronzo of Pawtucket, Rhode Island. Using a hair dryer, contestants must maneuver a Ping-Pong ball into a three-dimensional "bullseye" target.

  17. 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...... mobilities. In particular the article discusses 1) the physical city, its infrastructures and technological hardware/software, 2) policies and planning strategies for urban mobility and 3) the lived everyday life in the city and the region.......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 the so-called ‘mobility turn’ within social science. The perspective is illustrative for the research efforts at the Centre for Mobility and Urban Studies (C-MUS), Aalborg University. The article presents the contours of a theoretical perspective meeting the challenges to research into contemporary urban...

  18. 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 ...

  19. 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 ( ...

  20. Sprains and Strains

    Science.gov (United States)

    ... wrestling put people at risk for strains. Gymnastics, tennis, rowing, golf, and other sports that require extensive gripping can increase the risk of hand and forearm strains. Elbow strains sometimes occur in people who participate in ...

  1. Challenge of Biotechnology (Review Paper

    Directory of Open Access Journals (Sweden)

    Malcolm R. Dando

    2001-10-01

    Full Text Available The unravelling of the human genetic code whose first draft was announced in June 2000 has rightly blood been hailed as a momentous achievement, opening thc book of life, certain to be the dominant technology of the 21st century, which will inform all about medicine and biology. and lead us to a total understanding of life. Simultaneously, concerns have been expressed about thc implications of this work. In the past, major new technologies have been used intensively for hostile purposes. What is thc challenge that biotechnology poses in this regard'? This review paper looks at the enormous changes in civil society that thc genomics revolution could bring. Against this background, thc growing concerns about its potential misuses have been reviewed. Thc strengths and weaknesses or the Biological and Toxin Weapons Convention (BTWC are then touched upon. The BTWC presently lacks an adequate verification mechanism. Although biotechnology has been used by human beings since prehistoric times (eg. making of bread. cheese. wines its scientific understanding came only in the latter part of the 19th century. Thc decisive turning point in the field came in the 1970s with the advent of genetic engineering. In the military context classical agents like anthrax and toxin remain the threat today. Although thc current level or sophistication for many biological agents is low, there is enormous potential for making more sophisticated weapons. It might be possible to specifically target the genetic makeup of different ethnic groups. The limited varieties of staple crops and the limited strains of modern animals make agriculture particularly open to attack. Another serious possibility is the impact of genomics in neuroscience. With a better understanding of cellular receptor systems and bioregulators, it is not inconceivable that new means would be evolved for disturbing the functions of the nervous system. Thc genomics revolution can be used for peaceful purposes

  2. Computational prediction of neutralization epitopes targeted by human anti-V3 HIV monoclonal antibodies.

    Directory of Open Access Journals (Sweden)

    Evgeny Shmelkov

    Full Text Available The extreme diversity of HIV-1 strains presents a formidable challenge for HIV-1 vaccine design. Although antibodies (Abs can neutralize HIV-1 and potentially protect against infection, antibodies that target the immunogenic viral surface protein gp120 have widely variable and poorly predictable cross-strain reactivity. Here, we developed a novel computational approach, the Method of Dynamic Epitopes, for identification of neutralization epitopes targeted by anti-HIV-1 monoclonal antibodies (mAbs. Our data demonstrate that this approach, based purely on calculated energetics and 3D structural information, accurately predicts the presence of neutralization epitopes targeted by V3-specific mAbs 2219 and 447-52D in any HIV-1 strain. The method was used to calculate the range of conservation of these specific epitopes across all circulating HIV-1 viruses. Accurately identifying an Ab-targeted neutralization epitope in a virus by computational means enables easy prediction of the breadth of reactivity of specific mAbs across the diversity of thousands of different circulating HIV-1 variants and facilitates rational design and selection of immunogens mimicking specific mAb-targeted epitopes in a multivalent HIV-1 vaccine. The defined epitopes can also be used for the purpose of epitope-specific analyses of breakthrough sequences recorded in vaccine clinical trials. Thus, our study is a prototype for a valuable tool for rational HIV-1 vaccine design.

  3. Challenging Identities

    DEFF Research Database (Denmark)

    Keydar, Ceglar; Marin, Manuela; Janik, Allan;

    , cultural, and political practices. Notions of national identity and national politics are challenged by European integration, as well as by increasing demographic heterogeneity due to migration, and migrants experience conflicts of identification stemming from clashes between cultural heritage...... and the cultures of the new habitat. European horizons—frames of mind, historical memories, and expectations at the level of groups or communities, at the national level, and at the general European level—are at odds. Analyzing a series of issues in European countries from Turkey to Spain and from Scandinavia...

  4. Screening and Analysis of Janelia FlyLight Project Enhancer-Gal4 Strains Identifies Multiple Gene Enhancers Active During Hematopoiesis in Normal and Wasp-Challenged Drosophila Larvae.

    Science.gov (United States)

    Tokusumi, Tsuyoshi; Tokusumi, Yumiko; Brahier, Mark S; Lam, Victoria; Stoller-Conrad, Jessica R; Kroeger, Paul T; Schulz, Robert A

    2017-02-09

    A GFP expression screen has been conducted on >1000 Janelia FlyLight Project enhancer-Gal4 lines to identify transcriptional enhancers active in the larval hematopoietic system. A total of 190 enhancers associated with 87 distinct genes showed activity in cells of the third instar larval lymph gland and hemolymph. That is, gene enhancers were active in cells of the lymph gland posterior signaling center (PSC), medullary zone (MZ), and/or cortical zone (CZ), while certain of the transcriptional control regions were active in circulating hemocytes. Phenotypic analyses were undertaken on 81 of these hematopoietic-expressed genes, with nine genes characterized in detail as to gain- and loss-of-function phenotypes in larval hematopoietic tissues and blood cells. These studies demonstrated the functional requirement of the cut gene for proper PSC niche formation, the hairy, Btk29A, and E2F1 genes for blood cell progenitor production in the MZ domain, and the longitudinals lacking, dFOXO, kayak, cap-n-collar, and delilah genes for lamellocyte induction and/or differentiation in response to parasitic wasp challenge and infestation of larvae. Together, these findings contribute substantial information to our knowledge of genes expressed during the larval stage of Drosophila hematopoiesis and newly identify multiple genes required for this developmental process.

  5. Screening and Analysis of Janelia FlyLight Project Enhancer-Gal4 Strains Identifies Multiple Gene Enhancers Active During Hematopoiesis in Normal and Wasp-Challenged Drosophila Larvae

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Tokusumi

    2017-02-01

    Full Text Available A GFP expression screen has been conducted on >1000 Janelia FlyLight Project enhancer-Gal4 lines to identify transcriptional enhancers active in the larval hematopoietic system. A total of 190 enhancers associated with 87 distinct genes showed activity in cells of the third instar larval lymph gland and hemolymph. That is, gene enhancers were active in cells of the lymph gland posterior signaling center (PSC, medullary zone (MZ, and/or cortical zone (CZ, while certain of the transcriptional control regions were active in circulating hemocytes. Phenotypic analyses were undertaken on 81 of these hematopoietic-expressed genes, with nine genes characterized in detail as to gain- and loss-of-function phenotypes in larval hematopoietic tissues and blood cells. These studies demonstrated the functional requirement of the cut gene for proper PSC niche formation, the hairy, Btk29A, and E2F1 genes for blood cell progenitor production in the MZ domain, and the longitudinals lacking, dFOXO, kayak, cap-n-collar, and delilah genes for lamellocyte induction and/or differentiation in response to parasitic wasp challenge and infestation of larvae. Together, these findings contribute substantial information to our knowledge of genes expressed during the larval stage of Drosophila hematopoiesis and newly identify multiple genes required for this developmental process.

  6. Diagnostic Challenges at SNS

    CERN Document Server

    Plum, M A

    2003-01-01

    The Spallation Neutron Source now being built in Oak Ridge, Tennessee, USA, accelerates an H- ion beam to 1000 MeV with an average power of 1.4 MW. The H- beam is then stripped to H+, compressed in a storage ring to a pulse length of 695 ns, and then directed onto a mercury neutron spallation target. Most of the acceleration is accomplished with superconducting rf cavities. The presence of these cavities, the high average beam power, and the large range of beam intensity in the storage ring, provide unique challenges to the beam diagnostics systems. In this talk we will discuss these challenges and some of our solutions, including the laser profile monitor system, the residual gas ionization profile monitors, and network attached devices. Measurements performed using prototype instrumentation will also be presented.

  7. 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...

  8. Behavioural analysis and susceptibility to CNS injury of four inbred strains of mice.

    Science.gov (United States)

    Royle, S J; Collins, F C; Rupniak, H T; Barnes, J C; Anderson, R

    1999-01-23

    Interpretation of data from gene targeting studies can be confounded by the inherent traits of the background inbred strains used in the generation of transgenic and null mutant mice. We have therefore compared the behaviour and response to CNS injury of four inbred strains commonly used in molecular genetic studies to produce models of neurological disease. Adult, male 129/Ola, BALB/c, C57BL/6 and FVB/N mice (2-4 months) were initially subjected to behavioural tests that comprised a neurological examination, determination of motor function and cognitive testing in the Morris water maze. Also the response to CNS injury following an acute kainic acid (KA) challenge (30 mg kg-1, i.p.) was determined. The 129/Ola and BALB/c strains showed significant motor deficits when compared with the C57BL/6 and FVB/N strains. In contrast, only the FVB/N strain showed evidence of apparent cognitive impairments in the water maze as evidenced by increased pathlengths to locate the escape platforms and impaired performance in a probe trial. In addition, the FVB/N strain showed the most severe seizure response and mortality rate (62%) following administration of KA (30 mg kg-1, i.p.). These behavioural changes were also associated with a greater degree of cell body and synaptophysin loss in the pyramidal CA3 hippocampal cell layer and astrogliosis 72-h post-dose. These data suggest that the FVB/N strain may not be the most suitable background strain for the development of new transgenic mice for the study of genes implicated in the learning and memory process.

  9. 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.

  10. Strain-level dissection of the contribution of the gut microbiome to human metabolic disease.

    Science.gov (United States)

    Zhang, Chenhong; Zhao, Liping

    2016-04-20

    The gut microbiota has been linked with metabolic diseases in humans, but demonstration of causality remains a challenge. The gut microbiota, as a complex microbial ecosystem, consists of hundreds of individual bacterial species, each of which contains many strains with high genetic diversity. Recent advances in genomic and metabolomic technologies are facilitating strain-level dissection of the contribution of the gut microbiome to metabolic diseases. Interventional studies and correlation analysis between variations in the microbiome and metabolome, captured by longitudinal sampling, can lead to the identification of specific bacterial strains that may contribute to human metabolic diseases via the production of bioactive metabolites. For example, high-quality draft genomes of prevalent gut bacterial strains can be assembled directly from metagenomic datasets using a canopy-based algorithm. Specific metabolites associated with a disease phenotype can be identified by nuclear magnetic resonance-based metabolomics of urine and other samples. Such multi-omics approaches can be employed to identify specific gut bacterial genomes that are not only correlated with detected metabolites but also encode the genes required for producing the precursors of those metabolites in the gut. Here, we argue that if a causative role can be demonstrated in follow-up mechanistic studies--for example, using gnotobiotic models--such functional strains have the potential to become biomarkers for diagnostics and targets for therapeutics.

  11. Targeted biopharmaceuticals for cancer treatment.

    Science.gov (United States)

    Zhou, Lufang; Xu, Ningning; Sun, Yan; Liu, Xiaoguang Margaret

    2014-10-01

    Cancer is a complex invasive genetic disease that causes significant mortality rate worldwide. Protein-based biopharmaceuticals have significantly extended the lives of millions of cancer patients. This article reviews the biological function and application of targeted anticancer biopharmaceuticals. We first discuss the specific antigens and core pathways that are used in the development of targeted cancer therapy. The innovative monoclonal antibodies, non-antibody proteins, and small molecules targeting these antigens or pathways are then reviewed. Finally, the current challenges in anticancer biopharmaceuticals development and the potential solutions to address these challenges are discussed.

  12. 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....

  13. Scrapheap Challenge

    CERN Document Server

    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, ...

  14. Target Oriented Drugs against Leishmania.

    Science.gov (United States)

    1980-01-31

    the leishmanial source. Leishmanial strains L32 Leishmania tropica LRC L32 L137 Leishmania tropica LRC L137 L52 Leishmania donovani LRC L52 These...RESOLUTION TEST CHAR] 0REPORT NUMBER I TARGET ORIENTED DRUGS AGAINST LEISHMANIA (First Annual Summary Report) 0URI ZEHAVI, PhD and JOSEPH EL-ON, PhD...GOVT ACCESSION NO. 3. RE PIENT.S CATALOG NUMBER A....*( - ) S. TYPE OF REPORT & PERIOD COVERED TARGET ORIENTED DRUGS AGAINST LEISHMANIA 6 FIRST

  15. 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.

  16. Regulatory challenges

    Energy Technology Data Exchange (ETDEWEB)

    Austvik, Ole Gunnar

    2003-07-01

    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

  17. 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.

  18. Targeting biodefense markets.

    Science.gov (United States)

    Olinger, Gene Garrard

    2009-10-01

    The "World Vaccine Congress 2009" held in Washington D.C. (April 20-23, 2009) sponsored several sessions focused on the vaccine market targeting biodefense. On day one of the congress, a panel discussion outlined the federal progress in medical countermeasure preparedness that included emerging infections, influenza, and biodefense focuses. The second day, a session focused on the biodefense vaccine market with both government and industry members discussing the opportunities and challenges associated with the budding market.

  19. 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.

  20. Target-oriented discovery of a new esterase-producing strain Enterobacter sp. ECU1107 for whole cell-catalyzed production of (2S,3R)-3-phenylglycidate as a chiral synthon of Taxol.

    Science.gov (United States)

    Zhou, Dong-Jie; Pan, Jiang; Yu, Hui-Lei; Zheng, Gao-Wei; Xu, Jian-He

    2013-07-01

    A new strain, Enterobacter sp. ECU1107, was identified among over 200 soil isolates using a two-step screening strategy for the enantioselective synthesis of (2S,3R)-3-phenylglycidate methyl ester (PGM), a key intermediate for production of a potent anticancer drug Taxol®. An organic-aqueous biphasic system was employed to reduce spontaneous hydrolysis of the substrate PGM and isooctane was found to be the most suitable organic solvent. The temperature and pH optima of the whole cell-mediated bioreaction were 40 °C and 6.0, respectively. Under these reaction conditions, the enantiomeric excess (ee(s)) of (2S,3R)-PGM recovered was greater than 99 % at approximately 50 % conversion. The total substrate loading in batch reaction could reach 600 mM. By using whole cells of Enterobacter sp. ECU1107, (2S,3R)-PGM was successfully prepared in decagram scale in a 1.0-l mechanically stirred reactor, affording the chiral epoxy ester in >99 % ee s and 43.5 % molar yield based on the initial load of racemic substrate.

  1. High Strain Rate Characterisation of Composite Materials

    DEFF Research Database (Denmark)

    Eriksen, Rasmus Normann Wilken

    The high strain rate characterisation of FRP materials present the experimenter with a new set of challenges in obtaining valid experimental data. These challenges were addressed in this work with basis in classic wave theory. The stress equilibrium process for linear elastic materials, as fibre...... a linear elastic specimen to reach a state of constant strain rate before fracture. This was in contrast to ductile materials, which are widely tested with for the High-speed servohydraulic test machine. The development of the analysis and the interpretation of the results, were based on the experience...... Hopkinson Pressure Bar was addressed in terms of a new wave mechanics model for a linear elastic specimen the Split Hopkinson Pressure Bar. The model was formulated without any assumption of stress equilibrium, constant strain rate, or equal bars and thus provided a useful tool to analyse the equilibrium...

  2. 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.

  3. Obturator internus muscle strains

    Directory of Open Access Journals (Sweden)

    Caoimhe Byrne, MB BCh, BAO

    2017-03-01

    Full Text Available We report 2 cases of obturator internus muscle strains. The injuries occurred in young male athletes involved in kicking sports. Case 1 details an acute obturator internus muscle strain with associated adductor longus strain. Case 2 details an overuse injury of the bilateral obturator internus muscles. In each case, magnetic resonance imaging played a crucial role in accurate diagnosis.

  4. Target engagement in lead generation.

    Science.gov (United States)

    Durham, Timothy B; Blanco, Maria-Jesus

    2015-03-01

    The pharmaceutical industry is currently facing multiple challenges, in particular the low number of new drug approvals in spite of the high level of R&D investment. In order to improve target selection and assess properly the clinical hypothesis, it is important to start building an integrated drug discovery approach during Lead Generation. This should include special emphasis on evaluating target engagement in the target tissue and linking preclinical to clinical readouts. In this review, we would like to illustrate several strategies and technologies for assessing target engagement and the value of its application to medicinal chemistry efforts.

  5. 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...

  6. Finite Element Verification of Non-Homogeneous Strain and Stress Fields during Composite Material Testing

    DEFF Research Database (Denmark)

    Mikkelsen, Lars Pilgaard

    2015-01-01

    strength and fatigue performance is essential. Nevertheless, testing composites includes some challenges regarding stiffness determination using conventional strain gauges and achieving correct material failure unaffected by the gripping region during fatigue testing. Challenges, which in the present study...

  7. 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.

  8. A strain gauge

    DEFF Research Database (Denmark)

    2016-01-01

    The invention relates to a strain gauge of a carrier layer and a meandering measurement grid positioned on the carrier layer, wherein the strain gauge comprises two reinforcement members positioned on the carrier layer at opposite ends of the measurement grid in the axial direction....... The reinforcement members are each placed within a certain axial distance to the measurement grid with the axial distance being equal to or smaller than a factor times the grid spacing. The invention further relates to a multi-axial strain gauge such as a bi-axial strain gauge or a strain gauge rosette where each...... of the strain gauges comprises reinforcement members. The invention further relates to a method for manufacturing a strain gauge as mentioned above....

  9. Development of quantitative PCR and metagenomics-based approaches for strain quantification of a defined mixed-strain starter culture.

    Science.gov (United States)

    Johansen, Pernille; Vindeløv, Jannik; Arneborg, Nils; Brockmann, Elke

    2014-05-01

    Although the strain composition of mixed cultures may hugely affect production of various fermented foods, such as e.g. cheese, tools for investigating it have so far been limited. In this study, two new approaches for quantification of seven Lactococcus lactis subsp. cremoris strains (S1-S7) in a defined mixed-strain starter culture were developed and verified. By mapping NGS reads from 47 sequenced L. lactis strains to de novo assembly contigs of the seven strains, two strain-specific sequence regions (SEQ1 and SEQ2) were identified for each strain for qPCR primer design (A1 and A2). The qPCR assays amplified their strain-specific sequence region target efficiently. Additionally, high reproducibility was obtained in a validation sample containing equal amounts of the seven strains, and assay-to-assay coefficients of variance (CVs) for six (i.e. S1, S2, S4-S7) of the seven strains correlated to the inter-plate CVs. Hence, at least for six strains, the qPCR assay design approach was successful. The metagenomics-based approach quantified the seven strains based on average coverage of SEQ1 and SEQ2 by mapping sequencing reads from the validation sample to the strain-specific sequence regions. Average coverages of the SEQ1 and SEQ2 in the metagenomics data showed CVs of ≤17.3% for six strains (i.e. S1-S4, S6, S7). Thus, the metagenomics-based quantification approach was considered successful for six strains, regardless of the strain-specific sequence region used. When comparing qPCR- and metagenomics-based quantifications of the validation sample, the identified strain-specific sequence regions were considered suitable and applicable for quantification at a strain level of defined mixed-strain starter cultures.

  10. 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.

  11. Survival and activity of individual bioaugmentation strains

    DEFF Research Database (Denmark)

    Dueholm, Morten Simonsen; G. Marquesa, Irina; Karst, Søren Michael;

    2015-01-01

    Successful application of bioaugmentation for enhanced degradation of environmental pollutants is often limited by the lack of methods to monitor the survival and activity of individual bioaugmentation strains. However, recent advancements in sequencing technologies and molecular techniques now...... allow us to address these limitations. Here a complementing set of general applicable molecular methods are presented that provides detailed information on the performance of individual bioaugmentation strains under in situ conditions. The approach involves genome sequencing to establish highly specific...... qPCR and RT-qPCR tools for cell enumerations and expression of involved genes, stable isotope probing to follow growth on the target compounds and GFP-tagging to visualize the bioaugmentation strains directly in samples, all in combination with removal studies of the target compounds. The concept...

  12. Therapeutic challenges of urosepsis.

    Science.gov (United States)

    Wagenlehner, F M E; Pilatz, A; Naber, K G; Weidner, W

    2008-10-01

    Urosepsis accounts for approximately 25% of all sepsis cases and may develop from a community or nosocomial acquired urinary tract infection (UTI). The underlying UTI is almost exclusively a complicated one with involvement of parenchymatous urogenital organs (e.g. kidneys, prostate). In urosepsis, as in other types of sepsis, the severity of sepsis depends mostly upon the host response. The treatment of urosepsis comprises four major aspects: Early goal directed therapy, early optimal pharmacodynamic exposure to antimicrobials, early control of the complicating factor in the urinary tract and specific sepsis therapy. Following these prerequisites there appear two major challenges that need to be addressed: Firstly, time from admission to therapy is critical; the shorter the time to effective treatment, the higher the success rate. This aspect has to become incorporated into the organisational process. Secondly, adequate initial antibiotic therapy has to be insured. This goal implies however, a wide array of measures to ensure rational antibiotic policy. Both challenges are best targeted if an interdisciplinary approach at any level of the process is established, encompassing urologists, intensive care specialists, radiologists, microbiologists and clinical pharmacologists working tightly together at any time.

  13. Job strain and the risk of stroke

    DEFF Research Database (Denmark)

    Fransson, Eleonor I; Nyberg, Solja T; Heikkilä, Katriina

    2015-01-01

    BACKGROUND AND PURPOSE: Psychosocial stress at work has been proposed to be a risk factor for cardiovascular disease. However, its role as a risk factor for stroke is uncertain. METHODS: We conducted an individual-participant-data meta-analysis of 196 380 males and females from 14 European cohort...... studies to investigate the association between job strain, a measure of work-related stress, and incident stroke. RESULTS: In 1.8 million person-years at risk (mean follow-up 9.2 years), 2023 first-time stroke events were recorded. The age- and sex-adjusted hazard ratio for job strain relative to no job....... CONCLUSION: Job strain may be associated with an increased risk of ischemic stroke, but further research is needed to determine whether interventions targeting job strain would reduce stroke risk beyond existing preventive strategies....

  14. 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.

  15. Fast flexible electronics with strained silicon nanomembranes.

    Science.gov (United States)

    Zhou, Han; Seo, Jung-Hun; Paskiewicz, Deborah M; Zhu, Ye; Celler, George K; Voyles, Paul M; Zhou, Weidong; Lagally, Max G; Ma, Zhenqiang

    2013-01-01

    Fast flexible electronics operating at radio frequencies (>1 GHz) are more attractive than traditional flexible electronics because of their versatile capabilities, dramatic power savings when operating at reduced speed and broader spectrum of applications. Transferrable single-crystalline Si nanomembranes (SiNMs) are preferred to other materials for flexible electronics owing to their unique advantages. Further improvement of Si-based device speed implies significant technical and economic advantages. While the mobility of bulk Si can be enhanced using strain techniques, implementing these techniques into transferrable single-crystalline SiNMs has been challenging and not demonstrated. The past approach presents severe challenges to achieve effective doping and desired material topology. Here we demonstrate the combination of strained- NM-compatible doping techniques with self-sustained-strain sharing by applying a strain-sharing scheme between Si and SiGe multiple epitaxial layers, to create strained print-transferrable SiNMs. We demonstrate a new speed record of Si-based flexible electronics without using aggressively scaled critical device dimensions.

  16. Three dimensional strained semiconductors

    Energy Technology Data Exchange (ETDEWEB)

    Voss, Lars; Conway, Adam; Nikolic, Rebecca J.; Leao, Cedric Rocha; Shao, Qinghui

    2016-11-08

    In one embodiment, an apparatus includes a three dimensional structure comprising a semiconductor material, and at least one thin film in contact with at least one exterior surface of the three dimensional structure for inducing a strain in the structure, the thin film being characterized as providing at least one of: an induced strain of at least 0.05%, and an induced strain in at least 5% of a volume of the three dimensional structure. In another embodiment, a method includes forming a three dimensional structure comprising a semiconductor material, and depositing at least one thin film on at least one surface of the three dimensional structure for inducing a strain in the structure, the thin film being characterized as providing at least one of: an induced strain of at least 0.05%, and an induced strain in at least 5% of a volume of the structure.

  17. Ribosomal Antibiotics: Contemporary Challenges

    Directory of Open Access Journals (Sweden)

    Tamar Auerbach-Nevo

    2016-06-01

    Full Text Available Most ribosomal antibiotics obstruct distinct ribosomal functions. In selected cases, in addition to paralyzing vital ribosomal tasks, some ribosomal antibiotics are involved in cellular regulation. Owing to the global rapid increase in the appearance of multi-drug resistance in pathogenic bacterial strains, and to the extremely slow progress in developing new antibiotics worldwide, it seems that, in addition to the traditional attempts at improving current antibiotics and the intensive screening for additional natural compounds, this field should undergo substantial conceptual revision. Here, we highlight several contemporary issues, including challenging the common preference of broad-range antibiotics; the marginal attention to alterations in the microbiome population resulting from antibiotics usage, and the insufficient awareness of ecological and environmental aspects of antibiotics usage. We also highlight recent advances in the identification of species-specific structural motifs that may be exploited for the design and the creation of novel, environmental friendly, degradable, antibiotic types, with a better distinction between pathogens and useful bacterial species in the microbiome. Thus, these studies are leading towards the design of “pathogen-specific antibiotics,” in contrast to the current preference of broad range antibiotics, partially because it requires significant efforts in speeding up the discovery of the unique species motifs as well as the clinical pathogen identification.

  18. Quantifying strain variability in modeling growth of Listeria monocytogenes

    NARCIS (Netherlands)

    Aryani, D.; Besten, den H.M.W.; Hazeleger, W.C.; Zwietering, M.H.

    2015-01-01

    Prediction of microbial growth kinetics can differ from the actual behavior of the target microorganisms. In the present study, the impact of strain variability on maximum specific growth rate (µmax) (h- 1) was quantified using twenty Listeria monocytogenes strains. The µmax was determined as functi

  19. Ribosomal DNA analysis of tsetse and non-tsetse transmitted Ethiopian Trypanosoma vivax strains in view of improved molecular diagnosis.

    Science.gov (United States)

    Fikru, Regassa; Matetovici, Irina; Rogé, Stijn; Merga, Bekana; Goddeeris, Bruno Maria; Büscher, Philippe; Van Reet, Nick

    2016-04-15

    Animal trypanosomosis caused by Trypanosoma vivax (T. vivax) is a devastating disease causing serious economic losses. Most molecular diagnostics for T. vivax infection target the ribosomal DNA locus (rDNA) but are challenged by the heterogeneity among T. vivax strains. In this study, we investigated the rDNA heterogeneity of Ethiopian T. vivax strains in relation to their presence in tsetse-infested and tsetse-free areas and its effect on molecular diagnosis. We sequenced the rDNA loci of six Ethiopian (three from tsetse-infested and three from tsetse-free areas) and one Nigerian T. vivax strain. We analysed the obtained sequences in silico for primer-mismatches of some commonly used diagnostic PCR assays and for GC content. With these data, we selected some rDNA diagnostic PCR assays for evaluation of their diagnostic accuracy. Furthermore we constructed two phylogenetic networks based on sequences within the smaller subunit (SSU) of 18S and within the 5.8S and internal transcribed spacer 2 (ITS2) to assess the relatedness of Ethiopian T. vivax strains to strains from other African countries and from South America. In silico analysis of the rDNA sequence showed important mismatches of some published diagnostic PCR primers and high GC content of T. vivax rDNA. The evaluation of selected diagnostic PCR assays with specimens from cattle under natural T. vivax challenge showed that this high GC content interferes with the diagnostic accuracy of PCR, especially in cases of mixed infections with T. congolense. Adding betain to the PCR reaction mixture can enhance the amplification of T. vivax rDNA but decreases the sensitivity for T. congolense and Trypanozoon. The networks illustrated that Ethiopian T. vivax strains are considerably heterogeneous and two strains (one from tsetse-infested and one from tsetse-free area) are more related to the West African and South American strains than to the East African strains. The rDNA locus sequence of six Ethiopian T. vivax

  20. 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

  1. 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

  2. Study on inhibiting the replication of the Edmonston strain of the measles virus using short hairpin RNA targeting the Rab9 GTPase gene in vitro%靶向Rab9GTPase基因shRNA体外抑制麻疹病毒Edmonston株复制的研究

    Institute of Scientific and Technical Information of China (English)

    史俊岩; 王美莲; 刘兵; 罗恩杰

    2011-01-01

    Objective To construct short hairpin RNA (shRNA) expression vectors targeting the Rab9 GTPase gene and to assess the inhibitory effect of shRNA on the expression of Rab9 GTPase and replication of the Edmonston strain of the measles virus in vitro. Methods A short hairpin RNA expression vector targeting the Rab9 GTPase gene was constructed in accordance with requirements for shRNA design and the Rab9 GTPase gene sequence, shRNA were transfected into Vero-E6 cells via liposomes, and then cells were infected with the Edmonston strain of the measles virus. The expression of Rab9 GTPase mRNA was assayed by RT-PCR, and the expression of Rab9 GTPase protein was observed using a Western blot assay. ShRNA-mediated inhibition of measles virus replication was studied by detecting the titer of the measles virus. Results Compared to the control group, shRNA targeting the Rab9 GTPase gene significantly inhibited the expression of Rab9 GTPase mRNA and protein in Vero-E6 cells, with a maximum inhibition rate of (86. 3±0.7)% and (87.6±0.7)%, respectively. Measles virus replication was suppressed dramatically and consistently by shRNA targeting the Rab9 GTPase gene; most importantly, this suppression persisted after 32 d. Conclusion shRNA targeting the Rab9 GTPase gene specially inhibited the expression of Rab9 GTPase and measles virus replication in vitro ;these shRNA can potentially be developed into therapeutic agents for the treatment of measles virus infection.%目的:构建靶向Rab9 GTPase基因的短发夹RNA(shRNA)表达载体,观察shRNA对Rab9 GTPase表达和麻疹病毒Edmonston株体外复制的抑制效应.方法:按照shRNA的设计要求和Rab9 GTPase基因序列构建靶向Rab9 GTPase基因shRNA表达载体,表达载体经酶切鉴定和序列分析后通过脂质体法转染Vero-E6细胞,然后感染麻疹病毒Edmonston株,通过RT-PCR和Western blot检测转染细胞内Rab9 GTPase mRNA和蛋白质的表达水平;通过标准蚀斑试验检测病毒滴度,

  3. Thank You, Challenges!

    Institute of Scientific and Technical Information of China (English)

    陈晨; 陈传光

    2016-01-01

    A person may meet many challenges in his or her life.Some people think challenges are terrible.But I think they’re great.And I want to say,"Thank you,challenges!"For some people,it’s hard to face the challenges because they are afraid of failing in the end.However,it’s necessary for a person to face the challenges.Challenges are good to~①you.

  4. 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.

  5. Evaluation of strain-specific primers for identification of Lactobacillus rhamnosus GG.

    Science.gov (United States)

    Endo, Akihito; Aakko, Juhani; Salminen, Seppo

    2012-12-01

    Lactobacillus rhamnosus strain GG (ATCC 53103) is one of the most widely studied and commercialized probiotic strains, and thus strain-specific identification for the strain is highly valuable. In this study, two published PCR-based identification methods for strain GG, a transposase gene-targeting system and a phage-related gene-targeting system, were evaluated. The former produced amplicons from eight of the 41 strains tested and the phage-related system from five of the tested strains, including the strain GG. Fingerprinting analysis indicated that the strains LMG 18025, LMG 18030, and LMG 18038, which had an amplicon by the former system but none by the latter, were genetically distinguishable from L. rhamnosus GG at strain level. Strains LMG 23320, LMG 23325, LMG 23534, and LMG 25859 showed profiles very similar to that of the strain GG, suggesting that these strains might be identical to GG or derivative strains of it. The results here indicated that the phage-related gene-targeting system is a good tool for accurate identification of L. rhamnosus GG. This system would be able to detect both the original L. rhamnosus GG and its derivative strains.

  6. Gene Targeting in Neuroendocrinology.

    Science.gov (United States)

    Candlish, Michael; De Angelis, Roberto; Götz, Viktoria; Boehm, Ulrich

    2015-09-20

    Research in neuroendocrinology faces particular challenges due to the complex interactions between cells in the hypothalamus, in the pituitary gland and in peripheral tissues. Within the hypothalamus alone, attempting to target a specific neuronal cell type can be problematic due to the heterogeneous nature and level of cellular diversity of hypothalamic nuclei. Because of the inherent complexity of the reproductive axis, the use of animal models and in vivo experiments are often a prerequisite in reproductive neuroendocrinology. The advent of targeted genetic modifications, particularly in mice, has opened new avenues of neuroendocrine research. Within this review, we evaluate various mouse models used in reproductive neuroendocrinology and discuss the different approaches to generate genetically modified mice, along with their inherent advantages and disadvantages. We also discuss a variety of versatile genetic tools with a focus on their potential use in reproductive neuroendocrinology.

  7. 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

  8. 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 broa......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...

  9. 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

  10. Target Space $\

    CERN Document Server

    Huggett, Nick

    2015-01-01

    This paper investigates the significance of T-duality in string theory: the indistinguishability with respect to all observables, of models attributing radically different radii to space -- larger than the observable universe, or far smaller than the Planck length, say. Two interpretational branch points are identified and discussed. First, whether duals are physically equivalent or not: by considering a duality of the familiar simple harmonic oscillator, I argue that they are. Unlike the oscillator, there are no measurements 'outside' string theory that could distinguish the duals. Second, whether duals agree or disagree on the radius of 'target space', the space in which strings evolve according to string theory. I argue for the latter position, because the alternative leaves it unknown what the radius is. Since duals are physically equivalent yet disagree on the radius of target space, it follows that the radius is indeterminate between them. Using an analysis of Brandenberger and Vafa (1989), I explain wh...

  11. Systems strategies for developing industrial microbial strains

    DEFF Research Database (Denmark)

    Lee, Sang Yup; Kim, Hyun Uk

    2015-01-01

    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...

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

    Science.gov (United States)

    Gorski, Lisa

    2012-01-01

    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.

  13. Blacklisting and the ban: contesting targeted sanctions in Europe

    NARCIS (Netherlands)

    de Goede, M.

    2011-01-01

    This article examines the practice of targeted sanctions as they are deployed against individuals and groups suspected of financing and facilitating terrorism in Europe. Substantial academic attention and critique has surrounded targeted sanctions and blacklists, as these practices challenge existin

  14. 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

    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...

  15. 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

  16. Practices for Enhancing Children's Social-Emotional Development and Preventing Challenging Behavior

    Science.gov (United States)

    Corso, Robert M.

    2007-01-01

    Many challenging behaviors can be prevented by designing environments that promote children's engagement and teaching children new social skills (Lawry, Danko, & Strain, 1999; Neilsen, Olive, Donovan, & McEvoy, 1999; Strain & Hemmeter, 1999). Fox, Dunlap, Hemmeter, Joseph, and Strain (2003) have described a framework for promoting children's…

  17. Hamstring strain - aftercare

    Science.gov (United States)

    ... Elsevier Saunders; 2015:chap 88. Reider B, Davies GJ, Provencher MT. Muscle strains about the hip and thigh. In: Reider B, Davies GJ, Provencher MT, eds. Orthopaedic Rehabilitation of the Athlete . ...

  18. 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...

  19. Specific detection and analysis of a probiotic Bifidobacterium strain in infant feces

    NARCIS (Netherlands)

    Kok, RG; DeWaal, A; Schut, F; Welling, GW; Weenk, G; Hellingwerf, KJ

    1996-01-01

    For specific detection of the probiotic Bifidobacterium sp. strain LW420 in infant feces and for rapid quality control of this strain in culture, three strain-specific 16S rRNA gene-targeted primers have been developed. These primers allow specific detection of the organism via PCR. Specificity of t

  20. Efficient screening of environmental isolates for Saccharomyces cerevisiae strains that are suitable for brewing.

    Science.gov (United States)

    Fujihara, Hidehiko; Hino, Mika; Takashita, Hideharu; Kajiwara, Yasuhiro; Okamoto, Keiko; Furukawa, Kensuke

    2014-01-01

    We developed an efficient screening method for Saccharomyces cerevisiae strains from environmental isolates. MultiPlex PCR was performed targeting four brewing S. cerevisiae genes (SSU1, AWA1, BIO6, and FLO1). At least three genes among the four were amplified from all S. cerevisiae strains. The use of this method allowed us to successfully obtain S. cerevisiae strains.

  1. Acinetobacter baumannii biofilms: variations among strains and correlations with other cell properties.

    Science.gov (United States)

    McQueary, Christin N; Actis, Luis A

    2011-04-01

    Acinetobacter baumannii is an opportunistic pathogen that causes serious infections in humans by colonizing and persisting on surfaces normally found in hospital settings. The capacity of this pathogen to persist in these settings could be due to its ability to form biofilms on inanimate surfaces. This report shows that although the ATCC 19606(T) type strain and 8 different clinical isolates form biofilms, there are significant variations in the cell density and microscopic structures of these cell aggregates, with 3 of the isolates forming pellicles floating on the surface of stagnant broth cultures. PCR indicated that, like ATCC 19606(T), all 8 clinical isolates harbor all the genetic components of the CsuA/BABCDE chaperone-usher pili assembly system, which is needed for biofilm formation on plastic. Pili detection in cells of all strains examined supports the presence and function of a pilus assembly system. However, only one of them produced the putative ATCC 19606(T) CsuA/B pilin subunit protein. Hydrophobicity tests and motility assays also showed significant variations among all tested strains and did not result in direct correlations between the biofilm phenotype and cell properties that could affect biofilm formation on abiotic surfaces. This lack of correlation among these 3 phenotypes may reflect some of the variations already reported with this pathogen, which may pose a challenge in the treatment of the infections this pathogen causes in humans using biofilm formation on abiotic surfaces as a target.

  2. 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.

  3. Waiting-time targets. Early learners.

    Science.gov (United States)

    Moore, Alison

    2007-04-05

    Thirteen 'early achiever' sites have volunteered to deliver the new 18-week target ahead of schedule. The sites have highlighted recurring issues for trusts aiming for 18 weeks: orthopaedics, audiology, endoscopy and some smaller specialties have all proved challenging. The target should be seen as a vital step towards a 'no unnecessary delay' system of working and thinking.

  4. Increased number of intestinal villous M cells in levamisole - pretreated weaned pigs experimentally infected with F4ac+ enterotoxigenic Escherichia coli strain

    Directory of Open Access Journals (Sweden)

    H. Valpotić

    2010-07-01

    Full Text Available Immunoprophylaxis of porcine postweaning colibacillosis (PWC caused by enterotoxigenic Escherichia coli (ETEC expressing F4 fimbriae is an unsolved problem. Just as ETEC strains can exploit intestinal microfold (M cells as the entry portal for infection, their high transcytotic ability make them an attractive target for mucosally delivered vaccines, adjuvants and therapeutics. We have developed a model of parenteral/oral immunization of 4-weeks-old pigs with either levamisole or vaccine candidate F4ac+ non-ETEC strain to study their effects on de novo differentiation of antigen-sampling M cells. Identification, localization and morphometric quantification of cytokeratin 18 positive M cells in the ileal mucosa of 6-weeks-old pigs revealed that they were: 1 exclusively located within villous epithelial layer, 2 significantly numerous (P< 0.01 in levamisole pretreated/challenged pigs, and 3 only slightly, but not significantly numerous in vaccinated/challenged pigs compared with non-pretreated/challenged control pigs. The fact that levamisole may affect the M cells frequency by increasing their numbers, makes it an interesting adjuvant to study development of an effective M cell-targeted vaccine against porcine PWC.

  5. Increased number of intestinal villous M cells in levamisole -pretreated weaned pigs experimentally infected with F4ac+ enterotoxigenic Escherichia coli strain

    Science.gov (United States)

    Valpotić, H.; Kovšca Janjatović, A.; Lacković, G.; Božić, F.; Dobranić, V.; Svoboda, D.; Valpotić, I.; Popović, M.

    2010-01-01

    Immunoprophylaxis of porcine postweaning colibacillosis (PWC) caused by enterotoxigenic Escherichia coli (ETEC) expressing F4 fimbriae is an unsolved problem. Just as ETEC strains can exploit intestinal microfold (M) cells as the entry portal for infection, their high transcytotic ability make them an attractive target for mucosally delivered vaccines, adjuvants and therapeutics. We have developed a model of parenteral/oral immunization of 4-weeks-old pigs with either levamisole or vaccine candidate F4ac+ non-ETEC strain to study their effects on de novo differentiation of antigen-sampling M cells. Identification, localization and morphometric quantification of cytokeratin 18 positive M cells in the ileal mucosa of 6-weeks-old pigs revealed that they were: 1) exclusively located within villous epithelial layer, 2) significantly numerous (P< 0.01) in levamisole pretreated/challenged pigs, and 3) only slightly, but not significantly numerous in vaccinated/challenged pigs compared with non-pretreated/challenged control pigs. The fact that levamisole may affect the M cells frequency by increasing their numbers, makes it an interesting adjuvant to study development of an effective M cell-targeted vaccine against porcine PWC. PMID:22073366

  6. 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...

  7. National Drug IQ Challenge

    Science.gov (United States)

    ... Reto nacional del coeficiente intelectual (CI) sobre las drogas y el alcohol 2016 National Drug IQ Challenge ... Reto nacional del coeficiente intelectual (CI) sobre las drogas y el alcohol 2015 National Drug IQ Challenge ...

  8. 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.

  9. LHC Status and Upgrade Challenges

    Science.gov (United States)

    Smith, Jeffrey

    2009-11-01

    The Large Hadron Collider has had a trying start-up and a challenging operational future lays ahead. Critical to the machine's performance is controlling a beam of particles whose stored energy is equivalent to 80 kg of TNT. Unavoidable beam losses result in energy deposition throughout the machine and without adequate protection this power would result in quenching of the superconducting magnets. A brief overview of the machine layout and principles of operation will be reviewed including a summary of the September 2008 accident. The current status of the LHC, startup schedule and upgrade options to achieve the target luminosity will be presented.

  10. 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…

  11. 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.

  12. 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

  13. Targeting autophagy in neurodegenerative diseases.

    Science.gov (United States)

    Vidal, René L; Matus, Soledad; Bargsted, Leslie; Hetz, Claudio

    2014-11-01

    The most prevalent neurodegenerative disorders involve protein misfolding and the aggregation of specific proteins. Autophagy is becoming an attractive target to treat neurodegenerative disorders through the selective degradation of abnormally folded proteins by the lysosomal pathway. However, accumulating evidence indicates that autophagy impairment at different regulatory steps may contribute to the neurodegenerative process. Thus, a complex scenario is emerging where autophagy may play a dual role in neurodegenerative diseases by causing the downstream effect of promoting the degradation of misfolded proteins and an upstream effect where its deregulation perturbs global proteostasis, contributing to disease progression. Challenges in the future development of therapeutic strategies to target the autophagy pathway are discussed.

  14. Muscle strain injuries.

    Science.gov (United States)

    Garrett, W E

    1996-01-01

    One of the most common injuries seen in the office of the practicing physician is the muscle strain. Until recently, little data were available on the basic science and clinical application of this basic science for the treatment and prevention of muscle strains. Studies in the last 10 years represent action taken on the direction of investigation into muscle strain injuries from the laboratory and clinical fronts. Findings from the laboratory indicate that certain muscles are susceptible to strain injury (muscles that cross multiple joints or have complex architecture). These muscles have a strain threshold for both passive and active injury. Strain injury is not the result of muscle contraction alone, rather, strains are the result of excessive stretch or stretch while the muscle is being activated. When the muscle tears, the damage is localized very near the muscle-tendon junction. After injury, the muscle is weaker and at risk for further injury. The force output of the muscle returns over the following days as the muscle undertakes a predictable progression toward tissue healing. Current imaging studies have been used clinically to document the site of injury to the muscle-tendon junction. The commonly injured muscles have been described and include the hamstring, the rectus femoris, gastrocnemius, and adductor longus muscles. Injuries inconsistent with involvement of a single muscle-tendon junction proved to be at tendinous origins rather than within the muscle belly. Important information has also been provided regarding injuries with poor prognosis, which are potentially repairable surgically, including injuries to the rectus femoris muscle, the hamstring origin, and the abdominal wall. Data important to the management of common muscle injuries have been published. The risks of reinjury have been documented. The early efficacy and potential for long-term risks of nonsteroidal antiinflammatory agents have been shown. New data can also be applied to the field

  15. 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

    2016-01-06

    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.

  16. Displacement fields denoising and strains extraction by finite element method

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Optical full-field measurement methods are now widely applied in various domains. In general,the displacement fields can be directly obtained from the measurement,however in mechanical analysis strain fields are preferred.To extract strain fields from noisy displacement fields is always a challenging topic.In this study,a finite element method for smoothing displacement fields and calculating strain fields is proposed.An experimental test case on a holed aluminum specimen under tension is applied to vali...

  17. Tracking target signal strengths on a grid using sparsity

    NARCIS (Netherlands)

    Farahmand, S.; Giannakis, G.B.; Leus, G.J.T.; Tian, Z.

    2014-01-01

    Multi-target tracking is mainly challenged by the nonlinearity present in the measurement equation and the difficulty in fast and accurate data association. To overcome these challenges, the present paper introduces a grid-based model in which the state captures target signal strengths on a known sp

  18. 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.

  19. 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.

  20. Identification of Bacillus strains for biological control of catfish pathogens.

    Directory of Open Access Journals (Sweden)

    Chao Ran

    Full Text Available Bacillus strains isolated from soil or channel catfish intestine were screened for their antagonism against Edwardsiella ictaluri and Aeromonas hydrophila, the causative agents of enteric septicemia of catfish (ESC and motile aeromonad septicaemia (MAS, respectively. Twenty one strains were selected and their antagonistic activity against other aquatic pathogens was also tested. Each of the top 21 strains expressed antagonistic activity against multiple aquatic bacterial pathogens including Edwardsiella tarda, Streptococcus iniae, Yersinia ruckeri, Flavobacterium columnare, and/or the oomycete Saprolegnia ferax. Survival of the 21 Bacillus strains in the intestine of catfish was determined as Bacillus CFU/g of intestinal tissue of catfish after feeding Bacillus spore-supplemented feed for seven days followed by normal feed for three days. Five Bacillus strains that showed good antimicrobial activity and intestinal survival were incorporated into feed in spore form at a dose of 8×10(7 CFU/g and fed to channel catfish for 14 days before they were challenged by E. ictaluri in replicate. Two Bacillus subtilis strains conferred significant benefit in reducing catfish mortality (P<0.05. A similar challenge experiment conducted in Vietnam with four of the five Bacillus strains also showed protective effects against E. ictaluri in striped catfish. Safety of the four strains exhibiting the strongest biological control in vivo was also investigated in terms of whether the strains contain plasmids or express resistance to clinically important antibiotics. The Bacillus strains identified from this study have good potential to mediate disease control as probiotic feed additives for catfish aquaculture.

  1. Well Conductor Strain Monitoring

    Science.gov (United States)

    2014-05-06

    comply with a collection of information if it does not display a currently valid OMB control number. 1. REPORT DATE JUL 2014 2. REPORT TYPE 3. DATES...849,429; filed on June 26, 2013 by the inventor, Dr. Anthony Ruffa and entitled “ SUBSEA WELL CONDUCTOR STRAIN MONITORING”. STATEMENT OF

  2. Challenges in the Heterologous Production of Antibiotics in Streptomyces.

    Science.gov (United States)

    Bekiesch, Paulina; Basitta, Patrick; Apel, Alexander K

    2016-08-01

    The fast growing genome databases provide us with a large number of so far unknown secondary metabolite biosynthetic gene clusters. A key method to study these gene clusters is their heterologous expression in an engineered host strain. Gene clusters derived from actinomycetes are usually expressed in a Streptomyces host strain to identify and investigate the corresponding compounds. However, heterologous expression is often accompanied with some challenges affecting the production rates of secondary metabolites. The first step is therefore the selection of a suitable expression vector and host strain. Once production has been established, there are several possibilities to improve compound yields either by media screens, by overexpression of regulatory or transport genes or by introduction of constitutive or inducible promoters. A surely important, but hitherto little studied factor is also the regulation of a heterologously expressed gene cluster by its host strain. This review gives a short overview on the chances and challenges provided by heterologous production of secondary metabolites in Streptomyces.

  3. 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.

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

    Science.gov (United States)

    Brown, Vienna R; Adney, Danielle R; Olea-Popelka, Francisco; Bowen, Richard A

    2015-01-01

    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.

  5. 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.

  6. 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.

  7. Biolarvicides in vector control : challenges and prospects

    OpenAIRE

    P.K.Mittal

    2003-01-01

    Biolarvicides, based on mosquitocidal toxins of certain strains of Bacillus sphaericus and Bacillusthuringiensis var israelensis H-14 (Bti) are highly effective against mosquito larvae at very lowdoses and safe to other non-target organisms. During past two decades various biolarvicide formulationsproduced in India and abroad have been tested at Malaria Research Centre and some formulationshave undergone large-scale operational trials. Biolarvicide formulations of B. sphaericusare useful in t...

  8. 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.

  9. Organic chemistry. Strain-release amination.

    Science.gov (United States)

    Gianatassio, Ryan; Lopchuk, Justin M; Wang, Jie; Pan, Chung-Mao; Malins, Lara R; Prieto, Liher; Brandt, Thomas A; Collins, Michael R; Gallego, Gary M; Sach, Neal W; Spangler, Jillian E; Zhu, Huichin; Zhu, Jinjiang; Baran, Phil S

    2016-01-15

    To optimize drug candidates, modern medicinal chemists are increasingly turning to an unconventional structural motif: small, strained ring systems. However, the difficulty of introducing substituents such as bicyclo[1.1.1]pentanes, azetidines, or cyclobutanes often outweighs the challenge of synthesizing the parent scaffold itself. Thus, there is an urgent need for general methods to rapidly and directly append such groups onto core scaffolds. Here we report a general strategy to harness the embedded potential energy of effectively spring-loaded C-C and C-N bonds with the most oft-encountered nucleophiles in pharmaceutical chemistry, amines. Strain-release amination can diversify a range of substrates with a multitude of desirable bioisosteres at both the early and late stages of a synthesis. The technique has also been applied to peptide labeling and bioconjugation.

  10. Alpha-1 antitrypsin is markedly decreased following pulmonary F. tularensis challenge

    Directory of Open Access Journals (Sweden)

    James Patrick Chambers

    2011-12-01

    Full Text Available Alpha-1 antitrypsin, a small glycoprotein clade A serpine serine protease inhibitor of neutrophil elastase has been shown to increase in humans following bacterial and viral infection. However, we report here significant reduction of this major inhibitor of elastase in plasma of F. tularensis LVS and SCHU S4 (Type A strain following pulmonary challenge. Consistent with an imbalance of protease-antiprotease function at the alveolar level in lungs of infected animals, increased elastase activity was observed in lung lavage fluids accompanied by decrease lung function, i.e., loss of lung elastance with concomitant increase of pulmonary hysteresistivity. These data are suggestive of targeted tissue destruction via unchecked neutrophhil elastase activity in infected animals.

  11. Directly probing the effect of strain on magnetic exchange interactions

    Science.gov (United States)

    Dorr, Kathrin

    2012-02-01

    Thin films of transition metal oxides of the perovskite type ABO3 (B = 3d or 4d metal) have revealed abundant examples for strain-driven changes of magnetic ordering. One most popular is the strain-induced ferromagnetic ferroelectric state of otherwise antiferromagnetic paraelectric EuTiO3. Another promising example is the strain control of orbital occupation and magnetic coupling at oxide interfaces of SrRuO3 with manganites. In spite of strong efforts, the theoretical treatment of magnetic exchange in complex oxides has remained a challenge, and experiments continue to show unpredicted / unexplained large effects of the epitaxial strains in films. In order to provide meaningful experimental data on strain dependences, epitaxial thin films should be grown in various coherent strain states on different substrates without changing anything but the strain. This is inherently difficult: possible problems may arise from a strain-dependent oxidation level or microstructure. As a complementary approach, the in-plane strain of epitaxial oxide films can be controlled reversibly using a piezoelectric substrate, even though the accessible reversible strain of 0.1 -- 0.2% is an order of magnitude smaller. In my talk, I will address reversible-strain studies on La0.7Sr0.3MnO3, La1-xSrxCoO3 (x = 0, 0.2, 0.3) und SrRuO3 films, showing the strain response of the magnetic Curie temperature, the magnetization and the electrical resistance and discussing the current understanding of the strain effects on magnetic ordering. In La0.8Sr0.2CoO3, a strain-driven phase transition between ferromagnetic and spin-glass-like could be established by combining the piezoelectric substrate with a tuned buffer system providing varied as-grown strain states. In SrRuO3, a tetragonal tensile strain state shows a suppression of the ordered magnetic moment. Lattice parameters and symmetries of the films were determined by x-ray diffraction. It is noted that the atomic displacements (bond lengths and

  12. Targeting tumor suppressor genes for cancer therapy.

    Science.gov (United States)

    Liu, Yunhua; Hu, Xiaoxiao; Han, Cecil; Wang, Liana; Zhang, Xinna; He, Xiaoming; Lu, Xiongbin

    2015-12-01

    Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain-of-function mutations, in general, has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss-of-function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics.

  13. Target-oriented chaos control

    Energy Technology Data Exchange (ETDEWEB)

    Dattani, Justine [Centre for Mathematical Biology, Department of Mathematical Sciences, University of Bath, Bath BA2 7AY (United Kingdom); Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge CB3 0WA (United Kingdom); Blake, Jack C.H. [Centre for Mathematical Biology, Department of Mathematical Sciences, University of Bath, Bath BA2 7AY (United Kingdom); Hilker, Frank M., E-mail: f.hilker@bath.ac.uk [Centre for Mathematical Biology, Department of Mathematical Sciences, University of Bath, Bath BA2 7AY (United Kingdom)

    2011-10-31

    Designing intervention methods to control chaotic behavior in dynamical systems remains a challenging problem, in particular for systems that are difficult to access or to measure. We propose a simple, intuitive technique that modifies the values of the state variables directly toward a certain target. The intervention takes into account the difference to the target value, and is a combination of traditional proportional feedback and constant feedback methods. It proves particularly useful when the target corresponds to the equilibrium of the uncontrolled system, and is available or can be estimated from expert knowledge (e.g. in biology and economy). -- Highlights: → We propose a chaos control method that forces the system to a certain target. → The intervention takes into account the difference to the target value. → It can be seen as a combination of proportional and constant feedback methods. → The method is very robust and highly efficient in the long-term. → It is particularly applicable when suitable target values are known or available.

  14. 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.

  15. A comparison of strain calculation using digital image correlation and finite element software

    Science.gov (United States)

    Iadicola, M.; Banerjee, D.

    2016-08-01

    Digital image correlation (DIC) data are being extensively used for many forming applications and for comparisons with finite element analysis (FEA) simulated results. The most challenging comparisons are often in the area of strain localizations just prior to material failure. While qualitative comparisons can be misleading, quantitative comparisons are difficult because of insufficient information about the type of strain output. In this work, strains computed from DIC displacements from a forming limit test are compared to those from three commercial FEA software. Quantitative differences in calculated strains are assessed to determine if the scale of variations seen between FEA and DIC calculated strains constitute real behavior or just calculation differences.

  16. Identification of Bacillus strains for biological control of catfish pathogens.

    Science.gov (United States)

    Ran, Chao; Carrias, Abel; Williams, Malachi A; Capps, Nancy; Dan, Bui C T; Newton, Joseph C; Kloepper, Joseph W; Ooi, Ei L; Browdy, Craig L; Terhune, Jeffery S; Liles, Mark R

    2012-01-01

    Bacillus strains isolated from soil or channel catfish intestine were screened for their antagonism against Edwardsiella ictaluri and Aeromonas hydrophila, the causative agents of enteric septicemia of catfish (ESC) and motile aeromonad septicaemia (MAS), respectively. Twenty one strains were selected and their antagonistic activity against other aquatic pathogens was also tested. Each of the top 21 strains expressed antagonistic activity against multiple aquatic bacterial pathogens including Edwardsiella tarda, Streptococcus iniae, Yersinia ruckeri, Flavobacterium columnare, and/or the oomycete Saprolegnia ferax. Survival of the 21 Bacillus strains in the intestine of catfish was determined as Bacillus CFU/g of intestinal tissue of catfish after feeding Bacillus spore-supplemented feed for seven days followed by normal feed for three days. Five Bacillus strains that showed good antimicrobial activity and intestinal survival were incorporated into feed in spore form at a dose of 8×10(7) CFU/g and fed to channel catfish for 14 days before they were challenged by E. ictaluri in replicate. Two Bacillus subtilis strains conferred significant benefit in reducing catfish mortality (Pbiological control in vivo was also investigated in terms of whether the strains contain plasmids or express resistance to clinically important antibiotics. The Bacillus strains identified from this study have good potential to mediate disease control as probiotic feed additives for catfish aquaculture.

  17. 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.

  18. Indirect airway challenges

    NARCIS (Netherlands)

    Joos, GF; O'Connor, B; Anderson, SD; Chung, F; Cockcroft, DW; Dahlen, B; DiMaria, G; Foresi, A; Hargreave, FE; Holgate, ST; Inman, M; Lotvall, J; Magnussen, H; Polosa, R; Postma, DS; Riedler, J

    2003-01-01

    Indirect challenges act by causing the release of endogenous mediators that cause the airway smooth muscle to contract. This is in contrast to the direct challenges where agonists such as methacholine or histamine cause airflow limitation predominantly via a direct effect on airway smooth muscle. Di

  19. 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…

  20. Challenge and Change

    Science.gov (United States)

    Mehaffy, George L.

    2012-01-01

    In the past twenty years, various industries have been forever altered by technology: newspapers, book publishing, the photography business, and many more. Higher education too faces unprecedented challenges primarily driven by rapid changes in technology. To meet these challenges and adapt to these changes, new models are needed. Six challenges…

  1. 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

  2. What Are Sprains and Strains?

    Science.gov (United States)

    ... hands and arms a lot. Examples are gymnastics, tennis, rowing, and golf. People who play these sports sometimes strain their hand or arm. Elbow strains can also happen when playing sports. What ...

  3. Discovery of functional antibodies targeting ion channels.

    Science.gov (United States)

    Wilkinson, Trevor C I; Gardener, Matthew J; Williams, Wendy A

    2015-04-01

    Ion channels play critical roles in physiology and disease by modulation of cellular functions such as electrical excitability, secretion, cell migration, and gene transcription. Ion channels represent an important target class for drug discovery that has been largely addressed, to date, using small-molecule approaches. A significant opportunity exists to target these channels with antibodies and alternative formats of biologics. Antibodies display high specificity and affinity for their target antigen, and they have the potential to target ion channels very selectively. Nevertheless, isolating antibodies to this target class is challenging due to the difficulties in expression and purification of ion channels in a format suitable for antibody drug discovery in addition to the complexity of screening for function. In this article, we will review the current state of ion channel biologics discovery and the progress that has been made. We will also highlight the challenges in isolating functional antibodies to these targets and how these challenges may be addressed. Finally, we also illustrate successful approaches to isolating functional monoclonal antibodies targeting ion channels by way of a number of case studies drawn from recent publications.

  4. Study on correlation between ultrasound elastography strain ratio method and molybdenum target X-ray mammogra-phy for BI-RADS gradeⅣcomplicating breast cancer%超声弹性成像应变率比值法与X射线钼靶对BI-RADSⅣ级合并乳腺癌的相关性研究

    Institute of Scientific and Technical Information of China (English)

    王丹青; 杜睿; 陈颖; 张歆; 郑光宇; 朱雯婷; 石俊

    2015-01-01

    目的:探讨超声弹性成像(UE)-超声弹性应变率比值(SR)法与 X 射线钼靶对乳腺影像报告和数据系统(BI-RADS)Ⅳ级合并乳腺癌诊断的相关性。方法选择2013年1月至2015年6月该院手术切除并经病理学证实的乳腺恶性肿瘤患者60例,其X射线钼靶BI-RADSⅣ级及以上,对60例患者的UE评分及SR进行回顾性分析,并对SR值与X射线钼靶分级进行相关性分析。结果60例患者中,BI-RADSⅣ、Ⅴ、Ⅵ级平均UE评分/平均SR值结果分别为(4.15±0.15)分/3.09±0.14、(4.40±0.09)分/3.41±0.11、(4.85±0.15)分/3.88±0.12;BI-RADSⅣ~Ⅵ级间仅 BI-RADSⅣ级平均UE评分、平均SR与Ⅴ级比较,差异无统计学意义(P>0.05);SR值与BI-RADSⅣ~Ⅵ级呈正相关(r=0.086、0.154、0.282, P<0.05),且相关系数随等级上升而增大。结论 SR值与BI-RADS分级有较高相关性,二者联合应用对BI-RADSⅣ级及以上肿块有较高诊断价值。%Objective To investigate the correlation between the ultrasound elastography strain ratio (UE-SR) method and molybdenum target X-ray mammography for diagnosing the grade Ⅳcomplicating breast cancer. Methods 60 cases of breast imaging reporting and data system(BI-RADS) gradeⅣor more were selected from the patients with malignant breast tumor treat-ed by operation resection and confirmed by pathology in our hospital from Jan. 2013 to Jun. 2015 and their UE scores and SR re-sults were retrospectively analyzed. Furthermore the correlation of SR value and molybdenum target grade was analyzed. Results Among 60 cases,the average UE scores and SR values of BI-RADS gradeⅣ,Ⅴ,Ⅵwere(4.15±0.15) points/(3.09±0.14),(4.40± 0.09) points/(3.41±0.11) and (4.85±0.15) points/(3.88±0.12) respectively. The average UE scores and SR values had no statis-tical differences only between the BI-RADS gradeⅣand BI-RADS gradeⅤ(P>0.05). The SR value had a positive correlation with the

  5. Impact of litter Salmonella strain on the recovered Salmonella strains from broiler crop and ceca following feed withdrawal

    Science.gov (United States)

    To evaluate the impact of litter Salmonella status during feed withdrawal, 2 pens of 5-wk-old broilers (n=10/pen) in separate rooms were challenged with marker strains of either Salmonella Montevideo (nalidixic acid resistant) or Salmonella Heidelberg (streptomycin resistant) by oral gavage. Three ...

  6. 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.

  7. 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.

  8. 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.

  9. Yaws: towards the WHO eradication target

    Science.gov (United States)

    Marks, Michael

    2016-01-01

    In 2012 WHO declared a target to eradicate yaws by 2020. The cornerstone of this strategy is community mass treatment with azithromycin. Initial studies suggest this is a very effective tool that may be capable of interrupting transmission. Alongside this there has been progress in the development and validation of diagnostic tests for yaws. Several new challenges have also emerged, in particular, evidence that Haemophilus ducreyi can cause phenotypically similar ulcers in yaws endemic communities, and evidence for a possible non-human primate reservoir. The 2020 eradication target remains ambitious and more challenges should be expected on the journey. PMID:27268712

  10. Yaws: towards the WHO eradication target.

    Science.gov (United States)

    Marks, Michael

    2016-06-01

    In 2012 WHO declared a target to eradicate yaws by 2020. The cornerstone of this strategy is community mass treatment with azithromycin. Initial studies suggest this is a very effective tool that may be capable of interrupting transmission. Alongside this there has been progress in the development and validation of diagnostic tests for yaws. Several new challenges have also emerged, in particular, evidence that Haemophilus ducreyi can cause phenotypically similar ulcers in yaws endemic communities, and evidence for a possible non-human primate reservoir. The 2020 eradication target remains ambitious and more challenges should be expected on the journey.

  11. Potential probiotic Lactobacillus strains from fermented sausages: Further investigations on their probiotic properties

    NARCIS (Netherlands)

    Pennacchia, C.; Vaughan, E.E.; Villani, F.

    2006-01-01

    A rational selection of probiotic microorganisms is an important challenge and requires the definition of fundamental information about the physiology and genetics of candidate strains. In this study, selected Lactobacillus (Lact.) strains already characterized in a previous study for their capabili

  12. Surface strains induced by measured loads on teeth in vivo: a methodological study.

    Science.gov (United States)

    Nohl, F S; Setchell, D J

    2000-03-01

    Visual feedback enabled three subjects to apply predetermined near-axial loads to the incisal edge of an intact maxillary central incisor. In two subjects, principal strains and orientations developed on the labial surface of the intact incisor were resolved from strains recorded with a multiple element strain gauge. Load application was accurate and precise enough to allow resolution of strains induced by target loads of 10 to 50 N. Axially orientated compressive labial surface strains were induced by measured loads. The method could be used to validate bench-top stress analyses and investigate the effects of restoration on the structural integrity of teeth.

  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. Towards replacing closed with open target selection strategies

    NARCIS (Netherlands)

    Werf, M.J. van der

    2005-01-01

    Increasingly, microbial production processes are being improved by targeted approaches. In directed strain improvement, the selection of the relevant targets is the limiting step in metabolic engineering. Currently, the identification of leads is still a random process relying largely on expert know

  15. 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...

  16. 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.

  17. Big data challenges

    DEFF Research Database (Denmark)

    Bachlechner, Daniel; Leimbach, Timo

    2016-01-01

    Although reports on big data success stories have been accumulating in the media, most organizations dealing with high-volume, high-velocity and high-variety information assets still face challenges. Only a thorough understanding of these challenges puts organizations into a position in which...... they can make an informed decision for or against big data, and, if the decision is positive, overcome the challenges smoothly. The combination of a series of interviews with leading experts from enterprises, associations and research institutions, and focused literature reviews allowed not only...... framework are also relevant. For large enterprises and startups specialized in big data, it is typically easier to overcome the challenges than it is for other enterprises and public administration bodies....

  18. 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.

  19. 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)

  20. 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.

  1. Space mutagenesis of genetically engineered bacteria expressing recombinant human interferon α1b and screening of higher yielding strains.

    Science.gov (United States)

    Wang, Junfeng; Liu, Changting; Liu, Jinyi; Fang, Xiangqun; Xu, Chen; Guo, Yinghua; Chang, De; Su, Longxiang

    2014-03-01

    The aim of this study was to investigate the space mutagenesis of genetically engineered bacteria expressing recombinant human interferon α1b. The genetically engineered bacteria expressing the recombinant interferon α1b were sent into outer space on the Chinese Shenzhou VIII spacecraft. After the 17 day space flight, mutant strains that highly expressed the target gene were identified. After a series of screening of spaceflight-treated bacteria and the quantitative comparison of the mutant strains and original strain, we found five strains that showed a significantly higher production of target proteins, compared with the original strain. Our results support the notion that the outer space environment has unique effects on the mutation breeding of microorganisms, including genetically engineered strains. Mutant strains that highly express the target protein could be obtained through spaceflight-induced mutagenesis.

  2. 78 FR 19742 - Centennial Challenges: 2014 Night Rover Challenge

    Science.gov (United States)

    2013-04-02

    ... Rover Challenge purse is $1,500,000 (one million five hundred thousand U.S. dollars). Prizes will be... SPACE ADMINISTRATION Centennial Challenges: 2014 Night Rover Challenge AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Notice of Centennial Challenges 2014 Night Rover Challenge....

  3. Sadovskii vortex in strain

    Science.gov (United States)

    Freilich, Daniel; Llewellyn Smith, Stefan

    2014-11-01

    A Sadovskii vortex is a patch of fluid with uniform vorticity surrounded by a vortex sheet. Using a boundary element type method, we investigate the steady states of this flow in an incompressible, inviscid straining flow. Outside the vortex, the fluid is irrotational. In the limiting case where the entire circulation is due to the vortex patch, this is a patch vortex (Moore & Saffman, Aircraft wake turbulence and its detection 1971). In the other limiting case, where all the circulation is due to the vortex sheet, this is a hollow vortex (Llewellyn Smith and Crowdy, J. Fluid Mech. 691, 2012). This flow has two governing nondimensional parameters, relating the strengths of the straining field, vortex sheet, and patch vorticity. We study the relationship between these two parameters, and examine the shape of the resulting vortices. We also work towards a bifurcation diagram of the steady states of the Sadovskii vortex in an attempt to understand the connection between vortex sheet and vortex patch desingularizations of the point vortex. Support from NSF-CMMI-0970113.

  4. CANCER METASTASIS DIRECTLY ERADICATED BY TARGETED THERAPY WITHA MODIFIED SALMONELLA TYPHYMURIUM

    OpenAIRE

    Hayashi, Katsuhiro; Ming ZHAO; Yamauchi, Kensuke; Yamamoto, Norio; Tsuchiya, Hiroyuki; Tomita, Katsuro; Hoffman, Robert M.

    2009-01-01

    Cancer metastasis is the life-threatening aspect of cancer and is usually resistant to standard treatment. We report here a targeted therapy strategy for cancer metastasis using a modified strain of Salmonella typhimurium. The genetically modified strain of S. typhimurium is auxotrophic for the amino acids arginine and leucine. These mutations preclude growth in normal tissue but do not reduce bacterial virulence in tumor cells. The tumor-targeting strain of S. typhimurium, termed A1-R and ex...

  5. 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.

  6. 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.

  7. A distributed computational search strategy for the identification of diagnostics targets: application to finding aptamer targets for methicillin-resistant staphylococci.

    Science.gov (United States)

    Flanagan, Keith; Cockell, Simon; Harwood, Colin; Hallinan, Jennifer; Nakjang, Sirintra; Lawry, Beth; Wipat, Anil

    2014-06-30

    The rapid and cost-effective identification of bacterial species is crucial, especially for clinical diagnosis and treatment. Peptide aptamers have been shown to be valuable for use as a component of novel, direct detection methods. These small peptides have a number of advantages over antibodies, including greater specificity and longer shelf life. These properties facilitate their use as the detector components of biosensor devices. However, the identification of suitable aptamer targets for particular groups of organisms is challenging. We present a semi-automated processing pipeline for the identification of candidate aptamer targets from whole bacterial genome sequences. The pipeline can be configured to search for protein sequence fragments that uniquely identify a set of strains of interest. The system is also capable of identifying additional organisms that may be of interest due to their possession of protein fragments in common with the initial set. Through the use of Cloud computing technology and distributed databases, our system is capable of scaling with the rapidly growing genome repositories, and consequently of keeping the resulting data sets up-to-date. The system described is also more generically applicable to the discovery of specific targets for other diagnostic approaches such as DNA probes, PCR primers and antibodies.

  8. Peptide Vaccine: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Weidang Li

    2014-07-01

    Full Text Available Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

  9. Echocardiographic assessment of myocardial strain.

    Science.gov (United States)

    Gorcsan, John; Tanaka, Hidekazu

    2011-09-27

    Echocardiographic strain imaging, also known as deformation imaging, has been developed as a means to objectively quantify regional myocardial function. First introduced as post-processing of tissue Doppler imaging velocity converted to strain and strain rate, strain imaging has more recently also been derived from digital speckle tracking analysis. Strain imaging has been used to gain greater understanding into the pathophysiology of cardiac ischemia and infarction, primary diseases of the myocardium, and the effects of valvular disease on myocardial function, and to advance our understanding of diastolic function. Strain imaging has also been used to quantify abnormalities in the timing of mechanical activation for heart failure patients undergoing cardiac resynchronization pacing therapy. Further advances, such as 3-dimensional speckle tracking strain imaging, have emerged to provide even greater insight. Strain imaging has become established as a robust research tool and has great potential to play many roles in routine clinical practice to advance the care of the cardiovascular patient. This perspective reviews the physiology of myocardial strain, the technical features of strain imaging using tissue Doppler imaging and speckle tracking, their strengths and weaknesses, and the state-of-the-art present and potential future clinical applications.

  10. 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.

  11. 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/.

  12. 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.

  13. 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.

  14. 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.

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

    Science.gov (United States)

    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 ultralarge 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.

  16. Knockdown of genes in the Toll pathway reveals new lethal RNA interference targets for insect pest control.

    Science.gov (United States)

    Bingsohn, L; Knorr, E; Billion, A; Narva, K E; Vilcinskas, A

    2017-02-01

    RNA interference (RNAi) is a promising alternative strategy for ecologically friendly pest management. However, the identification of RNAi candidate genes is challenging owing to the absence of laboratory strains and the seasonality of most pest species. Tribolium castaneum is a well-established model, with a strong and robust RNAi response, which can be used as a high-throughput screening platform to identify potential RNAi target genes. Recently, the cactus gene was identified as a sensitive RNAi target for pest control. To explore whether the spectrum of promising RNAi targets can be expanded beyond those found by random large-scale screening, to encompass others identified using targeted knowledge-based approaches, we constructed a Cactus interaction network. We tested nine genes in this network and found that the delivery of double-stranded RNA corresponding to fusilli and cactin showed lethal effects. The silencing of cactin resulted in 100% lethality at every developmental stage from the larva to the adult. The knockdown of pelle, Dorsal-related immunity factor and short gastrulation reduced or even prevented egg hatching in the next generation. The combination of such targets with lethal and parental RNAi effects can now be tested against different pest species in field studies.

  17. Meeting global conservation challenges

    Science.gov (United States)

    2016-10-01

    Hot on the heels of last year's Sustainable Development Goals and the Paris Agreement, representatives from the global conservation community met to set the conservation agenda that will help to implement these targets.

  18. 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.

  19. Sorbitol production using recombinant Zymomonas mobilis strain.

    Science.gov (United States)

    Liu, Changjun; Dong, Hongwei; Zhong, Jianjiang; Ryu, Dewey D Y; Bao, Jie

    2010-07-20

    A recombinant Zymomonas mobilis strain harboring the plasmid pHW20a-gfo for over-expression of glucose-fructose oxidoreductase (GFOR) was constructed. The specific activity of GFOR enzyme in the new recombinant strain was at least two folds greater than that in the wild strain. The maximum GFOR activity achieved in terms of the volumetric, and the cellular were 2.59 U ml(-1), and 0.70 U mg(-1), respectively, in the batch cultures. A significant improvement of the bioconversion process for the production of sorbitol and gluconic acid from glucose and fructose was made using divalent metal ions which drastically reduced the ethanol yield and significantly increased the yield of target product. Among several divalent metal ions evaluated, Zn(2+) was found to be most effective by inhibiting the Entner-Doudoroff pathway enzymes. The yield of the byproduct ethanol was reduced from 16.7 to 1.8 gl(-1) and the sorbitol yield was increased to almost 100% from 89%. The Ca(2+) enhanced the sorbitol yield and the formation of calcium gluconate salt made the separation of gluconate from the reaction system easier.

  20. Reconstruction of strain distribution in fiber Bragg grat-ings with differential evolution algorithm

    Institute of Scientific and Technical Information of China (English)

    WEN Xiao-yan; YU Qoan

    2008-01-01

    Differential evolution algorithm is used to solve the inverse problem of strain distribution in tibet Bragg grating (FBG).Linear and nonlinear strain profiles are reconstructed based on the reflection spectra. An approximate solution could beobtained within only 50 rounds of evolutions. Numerical examples show good agreements between target strain profilesand reconstructed ones. Online performance analysis illuminates the efficiency and practicality of differential evolutionalgorithm in solving the inverse problem of FBG.

  1. Strain Pattern in Supercooled Liquids

    Science.gov (United States)

    Illing, Bernd; Fritschi, Sebastian; Hajnal, David; Klix, Christian; Keim, Peter; Fuchs, Matthias

    2016-11-01

    Investigations of strain correlations at the glass transition reveal unexpected phenomena. The shear strain fluctuations show an Eshelby-strain pattern [˜cos (4 θ ) /r2 ], characteristic of elastic response, even in liquids, at long times. We address this using a mode-coupling theory for the strain fluctuations in supercooled liquids and data from both video microscopy of a two-dimensional colloidal glass former and simulations of Brownian hard disks. We show that the long-ranged and long-lived strain signatures follow a scaling law valid close to the glass transition. For large enough viscosities, the Eshelby-strain pattern is visible even on time scales longer than the structural relaxation time τ and after the shear modulus has relaxed to zero.

  2. Performance Simulations of Moving Target Search Algorithms

    Directory of Open Access Journals (Sweden)

    Peter K. K. Loh

    2009-01-01

    Full Text Available The design of appropriate moving target search (MTS algorithms for computer-generated bots poses serious challenges as they have to satisfy stringent requirements that include computation and execution efficiency. In this paper, we investigate the performance and behaviour of existing moving target search algorithms when applied to search-and-capture gaming scenarios. As part of the investigation, we also introduce a novel algorithm known as abstraction MTS. We conduct performance simulations with a game bot and moving target within randomly generated mazes of increasing sizes and reveal that abstraction MTS exhibits competitive performance even with large problem spaces.

  3. Quantum Randi Challenge

    CERN Document Server

    Vongehr, Sascha

    2012-01-01

    Violations of Bell type inequalities in quantum experiments disprove all relativistic micro causal, classically real models. Desperate attempts at saving classicality retreated to claiming what Shimony calls a conspiracy. It is time to embrace the quantum paradigm instead of being stuck in defending it against positions on par with the belief in divinely planted fossils. However, different from 'quantum-magic' pseudoscience, there is resistance against quantum mechanics among scientific literate audiences, and it is growing. The Quantum Randi Challenge is designed to help scientists and educators discredit local realistic models and related attacks against quantum physics. Its 'Randi-type' properties are ensured via a simple computer game that can be made attractive and understandable to lay people. We introduce the general concept of a 'James Randi type' challenge as a tool for science outreach aimed against the spread of pseudoscience. This is a challenge which, according to the laws of nature as known to s...

  4. Complete Genome Sequence of Bacillus subtilis subsp. subtilis Strain 3NA

    OpenAIRE

    Reuß, Daniel R.; Schuldes, Jörg; Daniel, Rolf; Altenbuchner, Josef

    2015-01-01

    Bacillus subtilis 3NA reaches high cell densities during fed-batch fermentation and is an interesting target for further optimization as a production strain. Here, we announce the full genome of B. subtilis 3NA. The presence of specific Bacillus subtilis 168 and W23 genetic features suggests that 3NA is a hybrid of these strains.

  5. Experimentally induced infectious bovine keratoconjunctivitis: resistance of vaccinated cattle to homologous and heterologous strains of Moraxella bovis.

    Science.gov (United States)

    Pugh, G W; Hughes, D E; Schulz, V D; Graham, C K

    1976-01-01

    In studies to determine whether vaccination with one strain of Moraxella bovis would protect against challenge with virulent homologous or heterologous strains, calves were intramuscularly inoculated 3 times with formalin-killed M bovis, with 14 days between inoculations. Fourteen days after the 3rd vaccinal dose was given, all calves were exposed to homologous or heterologous virulent cultures of M bovis. The results indicated that vaccination with one strain of M bovis may induce protective immunity against homologous and heterologous challenge exposure; however, because vaccinated cattle resisted infection and disease produced by a homologous strain to a greater extent than they resisted those produced by heterologous strains, polyvalent vaccines or highly immunogenic common antigens may be needed to protect cattle against the numerous strains they might encounter under natural field conditions. There was minimal correlation between the presence of precipitating antibodies against the heterologous strains and the establishment of infection and disease.

  6. Evaluation of Strain Hardening Parameters

    Institute of Scientific and Technical Information of China (English)

    DING Zong-hai; Pavel Huml; YANG Wei

    2004-01-01

    The plane-strain compression test for three kinds of materials was carried out in a temperature range between room temperature and 400 ℃. The σ - ε curves and strain-hardening rate at different temperatures were simulated and a reasonable fit to the experimental data was obtained. A modified model created by data inference and computer simulation was developed to describe the strain hardening at a large deformation, and the predicted strain hardening are in a good agreement with that observed in a large range of stress. The influences of different parameters on strain hardening behaviour under large deformation were analysed. The temperature increase within the test temperatures for stainless steel 18/8 Ti results in dropping of flow stress and strain-hardening rate. For favourable γ-fibre texture to obtain high r, the cold rolling was applied at large reduction. In the experimental procedure, the X-ray diffraction test was carried out to compare the strain hardening and microstructure under large deformation for a bcc steel (low carbon steel SS-1142). The results indicate that the high strain-hardening rate possibly occurs when the primary slip plane {110} is parallel to the rolling plane and the strain-hardening rate decreases when lots of {110} plane rotate out from the orientation {110}∥RP.

  7. 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.

  8. 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.

  9. 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.

  10. Tumor targeting via integrin ligands

    Directory of Open Access Journals (Sweden)

    Udaya Kiran eMarelli

    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.

  11. Multiplexed modular genetic targeting of quantum dots.

    Science.gov (United States)

    Saurabh, Saumya; Beck, Lauren E; Maji, Suvrajit; Baty, Catherine J; Wang, Yi; Yan, Qi; Watkins, Simon C; Bruchez, Marcel P

    2014-11-25

    While DNA-directed nanotechnology is now a well-established platform for bioinspired nanoscale assembly in vitro, the direct targeting of various nanomaterials in living biological systems remains a significant challenge. Hybrid biological systems with integrated and targeted nanomaterials may have interesting and exploitable properties, so methods for targeting various nanomaterials to precise biological locations are required. Fluorescence imaging has benefited from the use of nanoparticles with superior optical properties compared to fluorescent organic dyes or fluorescent proteins. While single-particle tracking (SPT) in living cells with genetically encoded proteins is limited to very short trajectories, the high photon output of genetically targeted and multiplexed quantum dots (QDs) would enable long-trajectory analysis of multiple proteins. However, challenges with genetic targeting of QDs limit their application in these experiments. In this report, we establish a modular method for targeting QD nanoparticles selectively to multiple genetically encoded tags by precomplexing QD-streptavidin conjugates with cognate biotinylated hapten molecules. This approach enables labeling and SPT of multiple genetically encoded proteins on living cells at high speed and can label expressed proteins in the cytosol upon microinjection into living cells. While we demonstrate labeling with three distinct QD conjugates, the approach can be extended to other specific hapten-affinity molecule interactions and alternative nanoparticles, enabling precise directed targeting of nanoparticles in living biological systems.

  12. 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

  13. 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

  14. 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.

  15. Strain correction in interleaved strain-encoded (SENC) cardiac MR

    Science.gov (United States)

    Motaal, Abdallah G.; Osman, Nael F.

    2010-03-01

    The strain encoding (SENC) technique directly encodes regional strain of the heart into the acquired MR images and produces two images with two different tunings so that longitudinal strain, on the short-axis view, or circumferential strain on the long-axis view, are measured. Interleaving acquisition is used to shorten the acquisition time of the two tuned images by 50%, but it suffers from errors in the strain calculations due to inter-tunings motion of the heart. In this work, we propose a method to correct for the inter-tunings motion by estimating the motion-induced shift in the spatial frequency of the encoding pattern, which depends on the strain rate. Numerical data was generated to test the proposed method and real images of human subjects were used for validation. The proposed method corrected the measured strain values so they became nearly identical to the original ones. The results show an improvement in strain calculations so as to relax the imaging constraints on spatial and temporal resolutions and improve image quality.

  16. 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....

  17. Electrically charged targets

    Science.gov (United States)

    Goodman, Ronald K.; Hunt, Angus L.

    1984-01-01

    Electrically chargeable laser targets and method for forming such charged targets in order to improve their guidance along a predetermined desired trajectory. This is accomplished by the incorporation of a small amount of an additive to the target material which will increase the electrical conductivity thereof, and thereby enhance the charge placed upon the target material for guidance thereof by electrostatic or magnetic steering mechanisms, without adversely affecting the target when illuminated by laser energy.

  18. The Dirty Water Challenge

    Science.gov (United States)

    Walker, Mark; Kremer, Angelika; Schluter, Kirsten

    2007-01-01

    "The Dirty Water Challenge" is a fun activity that teaches children about their environment in an engaging and practical way. Inquiry is embedded within the practical--students have to design, plan, and then build their own design of water filter. Students are exposed to important concepts from a variety of scientific disciplines, including how…

  19. Challenges of Retrenchment.

    Science.gov (United States)

    Mingle, James R.; And Others

    The retrenchment experiences of a variety of institutions--large and small, public and private--are described and evaluated using an extensive spectrum of case studies sponsored by the Southern Regional Education Board. Part One discusses challenges of retrenchment (James R. Mingle) and strategies for the 1980s (David W. Breneman). Part Two,…

  20. 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.

  1. 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.

  2. 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…

  3. Challenges in data science

    DEFF Research Database (Denmark)

    Carbone, Anna; Jensen, M.; Sato, Aki-Hiro

    2016-01-01

    The ability to process and manage large data volumes has been proven to be not enough to tackle the current challenges presented by "Big Data". Deep insight is required for understanding interactions among connected systems, space- and time-dependent heterogeneous data structures. Emergence...

  4. Challenges of CE

    NARCIS (Netherlands)

    Verhagen, Wim J.C.; Stjepandić, Josip; Wognum, Nel

    2015-01-01

    Despite a long pedigree and many positive reports on its use and benefits, concurrent engineering (CE) and its associated research (sub)domains still experience significant development. In this final chapter, a socio-technical framework is applied to classify and analyze challenges identified as

  5. 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...

  6. Kayak Design Challenge

    Science.gov (United States)

    Wood, Anson

    2011-01-01

    Living in the Adirondack Park and being an avid outdoorsman has often resulted in the author's love of the outdoors working its way into class projects. In 2010, the author gave a group of 25 students in grades 9-12 a challenge that required them to design and construct a prototype inexpensive, lightweight kayak for backpackers and fisherman. In…

  7. 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...

  8. 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...

  9. 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.

  10. 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

  11. 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.

  12. 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…

  13. Anthropocene Age Wicked Challenges

    DEFF Research Database (Denmark)

    Edgeman, Rick; Wu, Zhaohui

    2015-01-01

    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...

  14. India's Higher Education Challenges

    Science.gov (United States)

    Altbach, Philip G.

    2014-01-01

    India, with the world's second largest higher education system and a rapidly growing economy as one of the BRIC nations, faces significant challenges in building both capacity and excellence in higher education. India's higher education system is characterized by "islands of excellence in a sea of mediocrity." The mainstream universities…

  15. 81 FR 54853 - Notice of Centennial Challenges Space Robotics Challenge

    Science.gov (United States)

    2016-08-17

    ... Space Robotics Challenge AGENCY: National Aeronautics and Space Administration (NASA). NOTICE: (16-056). ACTION: Notice of Centennial Challenges Space Robotics Challenge. SUMMARY: This notice is issued in accordance with 51 U.S.C. 20144(c). The Space Robotics Challenge is open and teams that wish to compete...

  16. 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...

  17. 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...

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

    Science.gov (United States)

    Bunting, E. A.; Provost, J.; Konofagou, E. E.

    2014-11-01

    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|ɛ)) 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.

  19. Strained graphene Hall bar

    Science.gov (United States)

    Milovanović, S. P.; Peeters, F. M.

    2017-02-01

    The effects of strain, induced by a Gaussian bump, on the magnetic field dependent transport properties of a graphene Hall bar are investigated. The numerical simulations are performed using both classical and quantum mechanical transport theory and we found that both approaches exhibit similar characteristic features. The effects of the Gaussian bump are manifested by a decrease of the bend resistance, R B, around zero-magnetic field and the occurrence of side-peaks in R B. These features are explained as a consequence of bump-assisted scattering of electrons towards different terminals of the Hall bar. Using these features we are able to give an estimate of the size of the bump. Additional oscillations in R B are found in the quantum description that are due to the population/depopulation of Landau levels. The bump has a minor influence on the Hall resistance even for very high values of the pseudo-magnetic field. When the bump is placed outside the center of the Hall bar valley polarized electrons can be collected in the leads.

  20. Occurrence of toxigenic Vibrio parahaemolyticus strains in shrimp in Iran.

    Science.gov (United States)

    Rahimi, Ebrahim; Ameri, Mehrdad; Doosti, Abbas; Gholampour, Ahmad Reza

    2010-09-01

    Vibrio parahaemolyticus, a common cause of foodborne gastroenteritis in people, is frequently isolated from a variety of seafood, including shrimp. The virulence of clinical V. parahaemolyticus strains is commonly associated with expression of thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH), which are encoded by the tdh and trh genes. This study was conducted to determine the prevalence rate of total and toxigenic V. parahaemolyticus in shrimp caught off the south coast of Iran. Three hundred freshly caught shrimp from four different species, Penaeus monodon, Penaeus semisulcatus, Penaeus indicus, and Penaeus merguiensis, were collected in three provinces along Persian Gulf in the south coast of Iran. Shrimp were collected at the end of each month from July 2008 to July 2009. The samples were analyzed for the presence of V. parahaemolyticus and the occurrence of toxigenic strains. Using conventional bacteriological techniques, 29 V. parahaemolyticus isolates were identified in which 28 strains were confirmed by a polymerase chain reaction assay targeting the tlh gene of V. parahaemolyticus. Using polymerase chain reaction assays targeting the tdh and trh genes, five (1.7%) and two (0.7%) isolates were tdh positive and trh positive, respectively. The tdh-positive isolates were commonly detected in summer, whereas no toxigenic strain was isolated in winter. To the best of our knowledge, the present study is the first report of the presence of toxigenic tdh- and trh-positive V. parahaemolyticus strains in the seafood in Iran.

  1. 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.

  2. Targeting FGFR Signaling in Cancer.

    Science.gov (United States)

    Touat, Mehdi; Ileana, Ecaterina; Postel-Vinay, Sophie; André, Fabrice; Soria, Jean-Charles

    2015-06-15

    The fibroblast growth factor signaling pathway (FGFR signaling) is an evolutionary conserved signaling cascade that regulates several basic biologic processes, including tissue development, angiogenesis, and tissue regeneration. Substantial evidence indicates that aberrant FGFR signaling is involved in the pathogenesis of cancer. Recent developments of deep sequencing technologies have allowed the discovery of frequent molecular alterations in components of FGFR signaling among several solid tumor types. Moreover, compelling preclinical models have demonstrated the oncogenic potential of these aberrations in driving tumor growth, promoting angiogenesis, and conferring resistance mechanisms to anticancer therapies. Recently, the field of FGFR targeting has exponentially progressed thanks to the development of novel agents inhibiting FGFs or FGFRs, which had manageable safety profiles in early-phase trials. Promising treatment efficacy has been observed in different types of malignancies, particularly in tumors harboring aberrant FGFR signaling, thus offering novel therapeutic opportunities in the era of precision medicine. The most exciting challenges now focus on selecting patients who are most likely to benefit from these agents, increasing the efficacy of therapies with the development of novel potent compounds and combination strategies, and overcoming toxicities associated with FGFR inhibitors. After examination of the basic and translational research studies that validated the oncogenic potential of aberrant FGFR signaling, this review focuses on recent data from clinical trials evaluating FGFR targeting therapies and discusses the challenges and perspectives for the development of these agents.

  3. Targeted Cancer Therapy Using Engineered Salmonella typhimurium.

    Science.gov (United States)

    Zheng, Jin Hai; Min, Jung-Joon

    2016-09-01

    Obligate or facultative anaerobic bacteria such as Bifidobacterium, Clostridium, Salmonella, or Escherichia coli specifically colonize and proliferate inside tumor tissues and inhibit tumor growth. Among them, attenuated Salmonella typhimurium (S. typhimurium) has been widely studied in animal cancer models and Phase I clinical trials in human patients. S. typhimurium genes are easily manipulated; thus diverse attenuated strains of S. typhimurium have been designed and engineered as tumor-targeting therapeutics or drug delivery vehicles that show both an excellent safety profile and therapeutic efficacy in mouse models. An attenuated strain of S. typhimurium, VNP20009, successfully targeted human metastatic melanoma and squamous cell carcinoma in Phase I clinical trials; however, the efficacy requires further refinement. Along with the characteristics of self-targeting, proliferation, and deep tissue penetration, the ease of genetic manipulation allows for the production of more attenuated strains with greater safety profiles and vector systems that deliver designable cargo molecules for cancer diagnosis and/or therapy. Here, we discuss recent progress in the field of Salmonellae-mediated cancer therapy.

  4. Targeted Cancer Therapy Using Engineered Salmonella typhimurium

    Science.gov (United States)

    Zheng, Jin Hai

    2016-01-01

    Obligate or facultative anaerobic bacteria such as Bifidobacterium, Clostridium, Salmonella, or Escherichia coli specifically colonize and proliferate inside tumor tissues and inhibit tumor growth. Among them, attenuated Salmonella typhimurium (S. typhimurium) has been widely studied in animal cancer models and Phase I clinical trials in human patients. S. typhimurium genes are easily manipulated; thus diverse attenuated strains of S. typhimurium have been designed and engineered as tumor-targeting therapeutics or drug delivery vehicles that show both an excellent safety profile and therapeutic efficacy in mouse models. An attenuated strain of S. typhimurium, VNP20009, successfully targeted human metastatic melanoma and squamous cell carcinoma in Phase I clinical trials; however, the efficacy requires further refinement. Along with the characteristics of self-targeting, proliferation, and deep tissue penetration, the ease of genetic manipulation allows for the production of more attenuated strains with greater safety profiles and vector systems that deliver designable cargo molecules for cancer diagnosis and/or therapy. Here, we discuss recent progress in the field of Salmonellae-mediated cancer therapy. PMID:27689027

  5. 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

  6. Discovery of Influenza A Virus Sequence Pairs and Their Combinations for Simultaneous Heterosubtypic Targeting that Hedge against Antiviral Resistance.

    Directory of Open Access Journals (Sweden)

    Keng Boon Wee

    2016-01-01

    Full Text Available The multiple circulating human influenza A virus subtypes coupled with the perpetual genomic mutations and segment reassortment events challenge the development of effective therapeutics. The capacity to drug most RNAs motivates the investigation on viral RNA targets. 123,060 segment sequences from 35,938 strains of the most prevalent subtypes also infecting humans-H1N1, 2009 pandemic H1N1, H3N2, H5N1 and H7N9, were used to identify 1,183 conserved RNA target sequences (≥15-mer in the internal segments. 100% theoretical coverage in simultaneous heterosubtypic targeting is achieved by pairing specific sequences from the same segment ("Duals" or from two segments ("Doubles"; 1,662 Duals and 28,463 Doubles identified. By combining specific Duals and/or Doubles to form a target graph wherein an edge connecting two vertices (target sequences represents a Dual or Double, it is possible to hedge against antiviral resistance besides maintaining 100% heterosubtypic coverage. To evaluate the hedging potential, we define the hedge-factor as the minimum number of resistant target sequences that will render the graph to become resistant i.e. eliminate all the edges therein; a target sequence or a graph is considered resistant when it cannot achieve 100% heterosubtypic coverage. In an n-vertices graph (n ≥ 3, the hedge-factor is maximal (= n- 1 when it is a complete graph i.e. every distinct pair in a graph is either a Dual or Double. Computational analyses uncover an extensive number of complete graphs of different sizes. Monte Carlo simulations show that the mutation counts and time elapsed for a target graph to become resistant increase with the hedge-factor. Incidentally, target sequences which were reported to reduce virus titre in experiments are included in our target graphs. The identity of target sequence pairs for heterosubtypic targeting and their combinations for hedging antiviral resistance are useful toolkits to construct target graphs for

  7. Generating embryonic stem cells from the inbred mouse strain DBA/2J, a model of glaucoma and other complex diseases.

    Directory of Open Access Journals (Sweden)

    Laura G Reinholdt

    Full Text Available Mouse embryonic stem (ES cells are derived from the inner cell mass of blastocyst stage embryos and are used primarily for the creation of genetically engineered strains through gene targeting. While some inbred strains of mice are permissive to the derivation of embryonic stem cell lines and are therefore easily engineered, others are nonpermissive or recalcitrant. Genetic engineering of recalcitrant strain backgrounds requires gene targeting in a permissive background followed by extensive backcrossing of the engineered allele into the desired strain background. The inbred mouse strain DBA/2J is a recalcitrant strain that is used as a model of many human diseases, including glaucoma, deafness and schizophrenia. Here, we describe the generation of germ-line competent ES cell lines derived from DBA/2J mice. We also demonstrate the utility of DBA/2J ES cells with the creation of conditional knockout allele for Endothelin-2 (Edn2 directly on the DBA/2J strain background.

  8. 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...

  9. Perishable Inventory Challenges

    DEFF Research Database (Denmark)

    Damgaard, Cecilie Maria; Nguyen, Vivi Thuy; Hvolby, Hans-Henrik

    2012-01-01

    The paper investigates how inventory control of perishable items is managed and line up some possible options of improvement. This includes a review of relevant literature dealing with the challenges of determining ordering policies for perishable products and a study of how the current procedure...... in the retail supply chains. The goal is to find and evaluate the parameters which affect the decision making process, when finding the optimal order quantity and order time. The paper takes a starting point in the retail industry but links to other industries.......The paper investigates how inventory control of perishable items is managed and line up some possible options of improvement. This includes a review of relevant literature dealing with the challenges of determining ordering policies for perishable products and a study of how the current procedures...

  10. GREEN BUILDING CHALLENGE 2005

    OpenAIRE

    López de Asiaín, Jaime; Alvarez-Ude, Luis

    2005-01-01

    Green Building Challenge 2005 forma part d'un projecte de cooperació entre diferents països (més de 20 en l'actualitat) que té per objectiu el desenvolupament d'una metodologia d'avaluació del comportament ecològic dels edificis i els resultats se presentaran en una conferència internacional a celebrar a Tòquio (Japó) a la finals de l'any 2005: Sustainable Building 2005. Green Building Challenge 2005 forma parte de un proyecto de cooperación entre distintos países (más de 20 en la actualid...

  11. 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...

  12. The challenge of conceiving

    DEFF Research Database (Denmark)

    Hansen, Claus Thorp; Jørgensen, Ulrik

    2011-01-01

    different or even not very well established ideas of what might be a good design result. We present two mutually supportive approaches to problem identification that we have developed, applied and refined. The first is providing an approach to map the arenas of development that influence the context......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...... 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 multitude of actors having...

  13. Challenges in Request Management

    DEFF Research Database (Denmark)

    Sommer, Anita Friis

    2014-01-01

    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...... 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...... 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....

  14. 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...

  15. 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-...

  16. 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

  17. A colonisation-inhibition culture consisting of Salmonella Enteritidis and Typhimurium ΔhilAssrAfliG strains protects against infection by strains of both serotypes in broilers.

    Science.gov (United States)

    De Cort, W; Mot, D; Haesebrouck, F; Ducatelle, R; Van Immerseel, F

    2014-08-06

    Consumption of contaminated poultry meat is still an important cause of Salmonella infections in humans and there is a need for control methods that protect broilers from day-of-hatch until slaughter age against infection with Salmonella. Colonisation-inhibition, a concept in which a live Salmonella strain is orally administered to day-old chickens and protects against subsequent challenge, can potentially be used as control method. In this study, the efficacy of a Salmonella Typhimurium ΔhilAssrAfliG strain as a colonisation-inhibition strain for protection of broilers against Salmonella Typhimurium was evaluated. Administration of a Salmonella Typhimurium ΔhilAssrAfliG strain to day-old broiler chickens decreased faecal shedding and strongly reduced caecal and internal organ colonisation of a Salmonella Typhimurium challenge strain administered one day later using a seeder bird model. In addition, it was verified whether a colonisation-inhibition culture could be developed that protects against both Salmonella Enteritidis and Typhimurium. Therefore, the Salmonella Typhimurium ΔhilAssrAfliG strain was orally administered simultaneously with a Salmonella Enteritidis ΔhilAssrAfliG strain to day-old broiler chickens, which resulted in a decreased caecal and internal organ colonisation for both a Salmonella Enteritidis and a Salmonella Typhimurium challenge strain short after hatching, using a seeder bird model. The combined culture was not protective against Salmonella Paratyphi B varietas Java challenge, indicating serotype-specific protection mechanisms. The data suggest that colonisation-inhibition can potentially be used as a versatile control method to protect poultry against several Salmonella serotypes.

  18. Ireland's Competitiveness Challenge 2011

    OpenAIRE

    2012-01-01

    The NCC publishes two annual competitiveness reports. Ireland's Competitiveness Challenge focuses on the national competitiveness issues of most importance to the enterprise sector and identifies policy recommendations required to address these issues. The report focuses on pursuing policies to improve competitiveness, particularly those to reduce the cost base for enterprise, to enhance the performance of the entire education system, and to deliver meaningful public sector reform. Ireland's ...

  19. 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

  20. Managing the Fukushima Challenge

    OpenAIRE

    Suzuki, Atsuyuki

    2014-01-01

    The Fukushima Daiichi accident raises a fundamental question: Can science and technology prevent the inevitability of serious accidents, especially those with low probabilities and high consequences? This question reminds us of a longstanding challenge with the trans-sciences, originally addressed by Alvin Weinberg well before the Three Mile Island and Chernobyl accidents. This article, revisiting Weinberg's issue, aims at gaining insights from the accident with a special emphasis on the soci...

  1. Gaddafi's Death Poses Challenges

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The death of Muammar Gaddafi marks a new era for Libya.It also poses a huge challenge for Libyan authorities dealing with tribal conflicts.He Wenping,a researcher with the Institute of West-Asian and African Studies at the Chinese Academy of Social Sciences,believes that Libya is in danger of falling into a period of internal strife and tribal conflict.

  2. 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

  3. Bioinformatics Challenge Days

    Science.gov (United States)

    2013-12-30

    concentrations 3. Genome Assembly for the Clinic: Performing de novo assembly from clinical samples with an emphasis on pathogen identification 4...The Illumina Genome Analyzer II was used. The sample contained 1.4 Gbp of data. DE NOVO GENETIC ASSEMBLY (BCD1, 2) The same datasets were used...Challenge (BCD1) 21   From Metagenomic Sample to Useful Visual (BCD1, 2) 21   De Novo Genetic Assembly (BCD1, 2) 22   Identifying Markers of Genetic

  4. 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.

  5. Cleanroom laboratory challenge overcome.

    Science.gov (United States)

    Quinn, Ronan

    2010-10-01

    Ronan Quinn, managing director of interior construction specialist Ardmac, describes the challenges of building and fitting out a new cleanroom laboratory for blood and bone marrow therapeutic treatment at Our Lady's Children's Hospital Crumlin in Dublin. The "state-of-the-art" facility, which fully complies with the recent EU Directive concerning human tissues and cells, has been well received by the client and end-users alike, but, as he explains, there were many obstacles to overcome during its completion.

  6. EDMS implementation challenge.

    Science.gov (United States)

    De La Torre, Marta

    2002-08-01

    The challenges faced by facilities wishing to implement an electronic medical record system are complex and overwhelming. Issues such as customer acceptance, basic computer skills, and a thorough understanding of how the new system will impact work processes must be considered and acted upon. Acceptance and active support are necessary from Senior Administration and key departments to enable this project to achieve measurable success. This article details one hospital's "journey" through design and successful implementation of an electronic medical record system.

  7. Strain-specific differentiation of lactococci in mixed starter culture populations using randomly amplified polymorphic DNA-derived probes.

    Science.gov (United States)

    Erlandson, K; Batt, C A

    1997-07-01

    A hydrophobic grid membrane filtration (HGMF) colony hybridization assay was developed that allows strain-specific differentiation of defined bacterial populations. The randomly amplified polymorphic DNA (RAPD) fingerprinting technique was used to identify potential signature nucleic acid sequences unique to each member of a commercial cheese starter culture blend. The blend consisted of two closely related Lactococcus lactis subsp. cremoris strains, 160 and 331, and one L. lactis subsp. lactis strain, 210. Three RAPD primers (OPX 1, OPX 12, and OPX 15) generated a total of 32 products from these isolates, 20 of which were potential strain-specific markers. Southern hybridization analyses revealed, that the RAPD-generated signature sequences OPX15-0.95 and a 0.36-kb HaeIII fragment of OPX1-1.0b were specific for strains 331 and 210, respectively, within the context of the test starter culture blend. These strain-specific probes were used in a HGMF colony hybridization assay. Colony lysis, hybridization, and nonradioactive detection parameters were optimized to allow specific differentiation and quantitation of the target strains in the mixed starter culture population. When the 210 and 331 probes were tested at their optimal hybridization temperatures against single cultures, they detected 100% of the target strain CFUs, without cross-reactivity to the other strains. The probes for strains 210 and 331 also successfully detected their targets in blended cultures even with a high background of the other two strains.

  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. Targeted Cancer Therapies

    Science.gov (United States)

    ... targeted therapies are directed against HER-2, including trastuzumab (Herceptin®), which is approved to treat certain breast and ... traditional chemotherapy drugs. For example, the targeted therapy trastuzumab (Herceptin®) has been used in combination with docetaxel , ...

  11. Microbial metabolomics: Replacing trial-and-error by the unbiased selection and ranking of targets

    NARCIS (Netherlands)

    Werf, M.J. van der; Jellema, R.H.; Hankemeier, T.

    2005-01-01

    Microbial production strains are currently improved using a combination of random and targeted approaches. In the case of a targeted approach, potential bottlenecks, feed-back inhibition, and side-routes are removed, and other processes of interest are targeted by overexpressing or knocking-out the

  12. Complete genome sequencing of Dehalococcoides sp. strain UCH007 using a differential reads picking method.

    Science.gov (United States)

    Uchino, Yoshihito; Miura, Takamasa; Hosoyama, Akira; Ohji, Shoko; Yamazoe, Atsushi; Ito, Masako; Takahata, Yoh; Suzuki, Ken-Ichiro; Fujita, Nobuyuki

    2015-01-01

    A novel Dehalococcoides sp. strain UCH007 was isolated from the groundwater polluted with chlorinated ethenes in Japan. This strain is capable of dechlorinating trichloroethene, cis-1,2-dichloroethene and vinyl chloride to ethene. Dehalococcoides bacteria are hardly cultivable, so genome sequencing has presented a challenge. In this study, we developed a differential reads picking method for mixed genomic DNA obtained from a co-culture, and applied it to the sequencing of strain UCH007. The genome of strain UCH007 consists of a 1,473,548-bp chromosome that encodes 1509 coding sequences including 29 putative reductive dehalogenase genes. Strain UCH007 is the first strain in the Victoria subgroup found to possess the pceA, tceA and vcrA genes.

  13. How to test brain and brain simulant at ballistic and blast strain rates.

    Science.gov (United States)

    Zhang, Jiangyue; Song, Bo; Pintar, Frank A; Yoganandan, Narayan; Chen, Weinong; Gennarelli, Thomas A

    2008-01-01

    Mechanical properties of brain tissue and brain simulant at strain rate in the range of 1000 s-1 are essential for computational simulation of intracranial responses for ballistic and blast traumatic brain injury. Testing these ultra-soft materials at high strain rates is a challenge to most conventional material testing methods. The current study developed a modified split Hopkinson bar techniques using the combination of a few improvements to conventional split Hopkinson bar including: using low impedance aluminum bar, semiconductor strain gauge, pulse shaping technique and annular specimen. Feasibility tests were conducted using a brain stimulant, Sylgard 527. Stress-strain curves of the simulant were successfully obtained at strain rates of 2600 and 2700 s-1 for strain levels up to 60%. This confirmed the applicability of Hopkinson bar for mechanical properties testing of brain tissue in the ballistic and blast domain.

  14. Proteomic Analysis of Outer Membrane Proteins from Salmonella Enteritidis Strains with Different Sensitivity to Human Serum

    Science.gov (United States)

    Dudek, Bartłomiej; Krzyżewska, Eva; Kapczyńska, Katarzyna; Rybka, Jacek; Pawlak, Aleksandra; Korzekwa, Kamila; Klausa, Elżbieta; Bugla-Płoskońska, Gabriela

    2016-01-01

    Differential analysis of outer membrane composition of S. Enteritidis strains, resistant to 50% normal human serum (NHS) was performed in order to find factors influencing the resistance to higher concentrations of NHS. Ten S. Enteritidis clinical strains, resistant to 50% NHS, all producing very long lipopolysaccharide, were subjected to the challenge of 75% NHS. Five extreme strains: two resistant and three sensitive to 75% NHS, were chosen for the further analysis of outer membrane proteins composition. Substantial differences were found in the levels of particular outer membrane proteins between resistant and sensitive strains, i.e. outer membrane protease E (PgtE) was present mainly in resistant strains, while sensitive strains possessed a high level of flagellar hook-associated protein 2 (FliD) and significantly higher levels of outer membrane protein A (OmpA). PMID:27695090

  15. 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.

  16. 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.

  17. Population structure of Spodoptera frugiperda maize and rice host forms in South America: are they host strains?

    NARCIS (Netherlands)

    Juárez, M.L.; Schöfl, G.; Vera, M.T.; Vilardi, J.C.; Murúa, M.G.; Willink, E.; Hänniger, S.; Heckel, D.G.; Groot, A.T.

    2014-01-01

    Determining which factors contribute to the formation and maintenance of genetic divergence to evaluate their relative importance as a cause of biological differentiation is among the major challenges in evolutionary biology. In Spodoptera frugiperda (Smith) (Lepidoptera: Noctuidae) two host strains

  18. Targeted therapies in hepatocellular carcinoma.

    Science.gov (United States)

    Bronte, F; Bronte, G; Cusenza, S; Fiorentino, E; Rolfo, C; Cicero, G; Bronte, E; Di Marco, V; Firenze, A; Angarano, G; Fontana, T; Russo, A

    2014-01-01

    The onset of hepatocellular carcinoma (HCC) is related to the development of non-neoplastic liver disease, such as viral infections and cirrhosis. Even though patients with chronic liver diseases undergo clinical surveillance for early diagnosis of HCC, this cancer is often diagnosed in advanced stage. In this case locoregional treatment is not possible and systemic therapies are the best way to control it. Until now sorafenib, a Raf and multi-kinase inhibitor has been the best, choice to treat HCC systemically. It showed a survival benefit in multicenter phase III trials. However the proper patient setting to treat is not well defined, since the results in Child-Pugh B patients are conflicting. To date various new target drugs are under developed and other biological treatments normally indicated in other malignancies are under investigation also for HCC. These strategies aim to target the different biological pathways implicated in HCC development and progression. The target drugs studied in HCC include anti-VEGF and anti-EGFR monoclonal antibodies, tyrosine kinase inhibitors and mTOR inhibitors. The most important challenge is represented by the best integration of these drugs with standard treatments to achieve improvement in overall survival and quality of life.

  19. 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...... 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...

  20. High Power Cryogenic Targets

    Energy Technology Data Exchange (ETDEWEB)

    Gregory Smith

    2011-08-01

    The development of high power cryogenic targets for use in parity violating electron scattering has been a crucial ingredient in the success of those experiments. As we chase the precision frontier, the demands and requirements for these targets have grown accordingly. We discuss the state of the art, and describe recent developments and strategies in the design of the next generation of these targets.

  1. Antiphospholipid syndrome: A diagnostic challenge.

    Science.gov (United States)

    Mallhi, R S; Kushwaha, Neerja; Chatterjee, T; Philip, J

    2016-12-01

    The antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilic disorder that is characterized by thrombosis (venous, arterial and microvascular) and obstetric morbidity due to a diverse family of antibodies against phospholipid-binding proteins present in plasma. The term antiphospholipid antibody is actually a misnomer as the antibodies are not against the phospholipid per se, but target the plasma protein co-factors, which bind to anionic PLs. The exact etiology has not been elucidated and is multifactorial. The initial guidelines for the diagnosis of APS were laid down in Sapporo, 1999, which were subsequently revised as the Sydney Consensus Conference criteria in 2006. Major changes were the inclusion of β2GPI as independent laboratory criteria, addition of ischemic stroke and transient cerebral ischemia as established clinical criteria and the requirement of repeating the test after 12 weeks. The laboratory tests recommended are coagulation assays, which study the effect of lupus anticoagulant on the clotting time and immunological assays, mostly ELISAs to detect IgG and IgM antibodies against cardiolipin and/or β2 glycoprotein I. For the diagnosis of APS, at least one clinical criterion and one laboratory criterion should be present. Limitations pertaining to the standardization, reproducibility and robustness of the currently recommended diagnostic tests still remain. Despite elaborate guidelines and syndrome defining criteria, the diagnosis of APS still remains a challenge. A greater interaction between the clinicians and the laboratory professionals is necessary for arriving at the correct diagnosis as a misdiagnosis of APS can have grave consequences.

  2. Less is more: structures of difficult targets with minimal constraints.

    Science.gov (United States)

    Lloyd, Neil R; Wuttke, Deborah S

    2014-09-01

    By merging recent experimental and computational methodology advances, resolution-adapted structural recombination Rosetta has emerged as a powerful strategy for solving the structure of traditionally challenging targets. In this issue of Structure, Sgourakis and colleagues solve the structure of one such target, the immunoevasin protein m04, using this approach.

  3. 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.

  4. Protection by attenuated and polyvalent vaccines against highly virulent strains of Marek's disease virus.

    Science.gov (United States)

    Witter, R L

    1982-01-01

    Tests confirmed that turkey herpesvirus (HVT) vaccine protected chickens poorly against challenge with the highly virulent Md5 strain of Marek's disease (MD) virus, especially in chickens with homologous HVT antibodies. The naturally avirulent SB-1 vaccine virus was likewise poorly protective against challenge with the Md5 strain. Homologous antibodies reduced the protective efficacy of both vaccines, but SB-1 was not affected by HVT antibodies. In order to provide better protection against strains of MD virus poorly protected against by HVT, such as Md5, the Md11 strain of MD virus was attenuated by 75 cell culture passages and evaluated for protective efficacy. This vaccine virus, designated Mdl 1/75C, provided good protection against challenge with Md5 and most other highly virulent MD viruses tested, but was less efficacious against challenge with the JM/102W strain, a prototype MD virus protected against well by HVT and SB-1 vaccines. Furthermore, its efficacy was consistently lower in chicks with HVT antibody. Thus, although HVT, SB-1, and Md11/75C were all efficacious against certain MD viruses, none of these vaccines protected optimally against all MD challenge viruses in all chickens. A polyvalent vaccine composed of Md11/75C, HVT and SB-1 viruses protected chickens better against a battery of five highly virulent MD challenge viruses, including three strains poorly protected against by HVT, than any single vaccine and was not influenced by HVT antibody. These data suggest that vaccinal immunity may be partially viral strain specific.

  5. A duplex PCR assay for the detection of Ralstonia solanacearum phylotype II strains in Musa spp.

    Directory of Open Access Journals (Sweden)

    Gilles Cellier

    Full Text Available 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.

  6. Current challenges in handling genetic data.

    Science.gov (United States)

    Blank, Patricia R; Gutzwiller, Felix

    2014-01-01

    In no other field of biomedicine has such revolutionary change taken place in recent decades as it has in molecular genetics. The accumulated knowledge in this field will not only enable clinicians to make new treatment decisions in future, but will also help to save on healthcare costs. A positive test result will be the prerequisite for carrying out targeted drug treatment (companion diagnostics). Specific molecular diagnostics provide doctors with additional information that was not previously available, enabling them to optimise treatment accordingly. At the same time, prognostic tests mean that targeted preventive measures can be taken. Highly informative non-invasive tests will enable early detection and prevention to play a greater role. Technological breakthroughs, such as high-throughput sequencing, will lead to a flood of data in the future. The challenge lies in the quality of interpretation, which means extracting useful information for doctor and patient. Unlike data collection, interpretation is complex and expensive: it requires a high degree of expertise and a lot of resources. At the same time, experts stress that - as well as improvements in the accuracy and speed of data analysis - defined quality criteria must be generated for reliable interpretation of results. These challenges need to be tackled so that the population can benefit to the utmost from the opportunities offered by these developments: rapidly available and informative tests for targeted therapies based on high-quality data.

  7. Presence of subclinical infection in gene-targeted human prion protein transgenic mice exposed to atypical bovine spongiform encephalopathy.

    Science.gov (United States)

    Wilson, Rona; Dobie, Karen; Hunter, Nora; Casalone, Cristina; Baron, Thierry; Barron, Rona M

    2013-12-01

    The transmission of bovine spongiform encephalopathy (BSE) to humans, leading to variant Creutzfeldt-Jakob disease has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health. Until recently, TSE disease in cattle was thought to be caused by a single agent strain, BSE, also known as classical BSE, or BSE-C. However, due to the initiation of a large-scale surveillance programme throughout Europe, two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H have since been discovered. To model the risk to human health, we previously inoculated these two forms of atypical BSE (BASE and BSE-H) into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP) (HuTg) but were unable to detect any signs of TSE pathology in these mice. However, despite the absence of TSE pathology, upon subpassage of some BASE-challenged HuTg mice, a TSE was observed in recipient gene-targeted bovine PrP Tg (Bov6) mice but not in HuTg mice. Disease transmission from apparently healthy individuals indicates the presence of subclinical BASE infection in mice expressing human PrP that cannot be identified by current diagnostic methods. However, due to the lack of transmission to HuTg mice on subpassage, the efficiency of mouse-to-mouse transmission of BASE appears to be low when mice express human rather than bovine PrP.

  8. Monoclonal Antibody Targeting Staphylococcus aureus Surface Protein A (SasA) Protect Against Staphylococcus aureus Sepsis and Peritonitis in Mice.

    Science.gov (United States)

    Yang, Yilong; Qian, Mengying; Yi, Shaoqiong; Liu, Shuling; Li, Bing; Yu, Rui; Guo, Qiang; Zhang, Xiaopeng; Yu, Changming; Li, Jianmin; Xu, Junjie; Chen, Wei

    2016-01-01

    Epidemic methicillin-resistant Staphylococcus aureus (MRSA) imposes an increasing impact on public health. Due to multi-antibiotics resistance in MRSA strains, there is an urgent need to develop novel therapeutics such as effective monoclonal antibodies (mAbs) against MRSA infections. Staphylococcus aureus surface protein A (SasA), a large surface-located protein (~240 kDa), is one of MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) and a potential target for immunotherapeutic approaches against S. aureus infections. In the present study, we analyzed the sequence of SasA with bioinformatics tools and generated a protective monoclonal antibody (2H7) targeting the conserved domain of SasA. 2H7 was shown to recognize wild-type S. aureus and promote opsonophagocytic killing of S. aureus. In both sepsis and peritoneal infection models, prophylactic administration of 2H7 improved the survival of BALB/c mice challenged by S. aureus strain USA300 and ST239 (prevalent MRSA clones in North America and Asian countries, respectively) and enhanced bacterial clearance in kidneys. Additionally, 2H7 prophylaxis prevented the formation of intraperitoneal abscess in a murine model of peritoneal infection and therapeutic administration of 2H7 showed protective efficacy in a murine sepsis model. Our results presented here provide supporting evidences that an anti-SasA mAb might be a potential component in an antibody-based immunotherapeutic treatment of MRSA infections.

  9. Protein-protein interactions as druggable targets: recent technological advances.

    Science.gov (United States)

    Higueruelo, Alicia P; Jubb, Harry; Blundell, Tom L

    2013-10-01

    Classical target-based drug discovery, where large chemical libraries are screened using inhibitory assays for a single target, has struggled to find ligands that inhibit protein-protein interactions (PPI). Nevertheless, in the past decade there have been successes that have demonstrated that PPI can be useful drug targets, and the field is now evolving fast. This review focuses on the new approaches and concepts that are being developed to tackle these challenging targets: the use of fragment based methods to explore the chemical space, stapled peptides to regulate intracellular PPI, alternatives to competitive inhibition and the use of antibodies to enable small molecule discovery for these targets.

  10. Target tracking in infrared imagery using a novel particle filter

    Institute of Scientific and Technical Information of China (English)

    Fanglin Wang; Erqi Liu; Jie Yang; Shengyang Yu; Yue Zhou

    2009-01-01

    To address two challenging problems in infrared target tracking, target appearance changes and unpre-dictable abrupt motions, a novel particle filtering based tracking algorithm is introduced. In this method, a novel saliency model is proposed to distinguish the salient target from background, and the eigenspace model is invoked to adapt target appearance changes. To account for the abrupt motions efficiently, a two-step sampling method is proposed to combine the two observation models. The proposed tracking method is demonstrated through two real infrared image sequences, which include the changes of luminance and size, and the drastic abrupt motions of the target.

  11. Therapeutic Approaches to Target Cancer Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Diaz, Arlhee, E-mail: arlhee@cim.sld.cu; Leon, Kalet [Department of Systems Biology, Center of Molecular Immunology, 216 Street, PO Box 16040, Atabey, Havana 11600 (Cuba)

    2011-08-15

    The clinical relevance of cancer stem cells (CSC) remains a major challenge for current cancer therapies, but preliminary findings indicate that specific targeting may be possible. Recent studies have shown that these tumor subpopulations promote tumor angiogenesis through the increased production of VEGF, whereas the VEGF neutralizing antibody bevacizumab specifically inhibits CSC growth. Moreover, nimotuzumab, a monoclonal antibody against the epidermal growth factor receptor (EGFR) with a potent antiangiogenic activity, has been shown by our group to reduce the frequency of CSC-like subpopulations in mouse models of brain tumors when combined with ionizing radiation. These studies and subsequent reports from other groups support the relevance of approaches based on molecular-targeted therapies to selectively attack CSC. This review discusses the relevance of targeting both the EGFR and angiogenic pathways as valid approaches to this aim. We discuss the relevance of identifying better molecular markers to develop drug screening strategies that selectively target CSC.

  12. Nanotechnology: Opportunities and Challenges

    Science.gov (United States)

    Meyyappan, Meyya

    2003-01-01

    Nanotechnology seeks to exploit novel physical, chemical, biological, mechanical, electrical, and other properties, which arise primarily due to the nanoscale nature of certain materials. A key example is carbon nanotubes (CNTs) which exhibit unique electrical and extraordinary mechanical properties and offer remarkable potential for revolutionary applications in electronics devices, computing, and data storage technology, sensors, composites, nanoelectromechanical systems (NEMS), and as tip in scanning probe microscopy (SPM) for imaging and nanolithography. Thus the CNT synthesis, characterization, and applications touch upon all disciplines of science and engineering. This presentation will provide an overview and progress report on this and other major research candidates in Nanotechnology and address opportunities and challenges ahead.

  13. Challenging the Innovation Paradigm

    CERN Document Server

    Sveiby, Karl Erik; Segercrantz, Beata

    2012-01-01

    Innovation is almost always seen as a "good thing". Challenging the Innovation Paradigm is a critical analysis of the innovation frenzy and contemporary innovation research. The one-sided focus on desirable effects of innovation misses many opportunities to reduce the undesirable consequences. Authors in this book show how systemic effects outside the innovating firms reduce the net benefits of innovation for individual employees, customers, as well as for society as a whole - also the innovators' own organizations. This book analyzes the dominant discourses that construct and recons

  14. Challenges in pharmacogenetics.

    Science.gov (United States)

    Cascorbi, Ingolf; Bruhn, Oliver; Werk, Anneke N

    2013-05-01

    The attempt to optimize drug treatment of patients by using evidenced-based medicine considering individual physiological and disease-related conditions is standard of modern medicine. Pharmacogenetics (PGx) has contributed to individualization considering hereditary genetic information; however, increasingly, pharmacogenomics is becoming essential, particularly in relation to modern oncology. New technologies such as next-generation sequencing and rapid development of computational and information sciences will help to better elucidate the consequences of genetic variation, considering also epigenetics and gene-environmental interactions and their translation into clinically relevant individual phenotypes. This review highlights the current challenging and most promising examples of PGx.

  15. Semantic Web Evaluation Challenge

    CERN Document Server

    2014-01-01

    This book constitutes the thoroughly refereed post conference proceedings of the first edition of the Semantic Web Evaluation Challenge, SemWebEval 2014, co-located with the 11th Extended Semantic Web conference, held in Anissaras, Crete, Greece, in May 2014. This book includes the descriptions of all methods and tools that competed at SemWebEval 2014, together with a detailed description of the tasks, evaluation procedures and datasets. The contributions are grouped in three areas: semantic publishing (sempub), concept-level sentiment analysis (ssa), and linked-data enabled recommender systems (recsys).

  16. Development of distributed target

    CERN Document Server

    Yu Hai Jun; Li Qin; Zhou Fu Xin; Shi Jin Shui; Ma Bing; Chen Nan; Jing Xiao Bing

    2002-01-01

    Linear introduction accelerator is expected to generate small diameter X-ray spots with high intensity. The interaction of the electron beam with plasmas generated at the X-ray converter will make the spot on target increase with time and debase the X-ray dose and the imaging resolving power. A distributed target is developed which has about 24 pieces of thin 0.05 mm tantalum films distributed over 1 cm. due to the structure adoption, the distributed target material over a large volume decreases the energy deposition per unit volume and hence reduces the temperature of target surface, then reduces the initial plasma formalizing and its expansion velocity. The comparison and analysis with two kinds of target structures are presented using numerical calculation and experiments, the results show the X-ray dose and normalized angle distribution of the two is basically the same, while the surface of the distributed target is not destroyed like the previous block target

  17. PLASTICITY AND NON-LINEAR ELASTIC STRAINS

    Science.gov (United States)

    conditions existing in plane waves in an extended medium to give the time rate of change of stress as a function of the time rate of change of strain, the stress invariants, the total strain and the plastic strain. (Author)

  18. Canning Tests on Mushroom Strain

    OpenAIRE

    Gormley, T. R. (Thomas Ronan); MacCanna, C.

    1980-01-01

    Canning tests were carried out on 5 mushroom strains from 2 flushes of 4 separate crops. Particular attention was given to the ratio of whole closed canned mushrooms to that of whole closed canned mushrooms plus canned stems and pieces - i.e. total yield. Factors considered in the tests included grading prior to processing, blanching and retort losses, shrinkage in size and mushroom whiteness. Cream and off-white strains had the highest level of open and misshapen mushrooms prior to processin...

  19. 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...

  20. Genome differences between Treponema pallidum subsp. pallidum strain Nichols and T. paraluiscuniculi strain Cuniculi A.

    Science.gov (United States)

    Strouhal, Michal; Smajs, David; Matejková, Petra; Sodergren, Erica; Amin, Anita G; Howell, Jerrilyn K; Norris, Steven J; Weinstock, George M

    2007-12-01

    The genome of Treponema paraluiscuniculi strain Cuniculi A was compared to the genome of the syphilis spirochete Treponema pallidum subsp. pallidum strain Nichols using DNA microarray hybridization, whole-genome fingerprinting, and DNA sequencing. A DNA microarray of T. pallidum subsp. pallidum Nichols containing all 1,039 predicted open reading frame PCR products was used to identify deletions and major sequence changes in the Cuniculi A genome. Using these approaches, deletions, insertions, and prominent sequence changes were found in 38 gene homologs and six intergenic regions of the Cuniculi A genome when it was compared to the genome of T. pallidum subsp. pallidum Nichols. Most of the observed differences were localized in tpr loci and the vicinity of these loci. In addition, 14 other genes were found to contain frameshift mutations resulting in major changes in protein sequences. Analysis of restriction target sites representing 0.34% of the total genome length and DNA sequencing of three PCR products (0.46% of the total genome length) amplified from Cuniculi A chromosomal regions and comparison to the Nichols genome revealed a sequence similarity of 98.6 to 99.3%. These results are consistent with a close genetic relationship among the T. pallidum strains and subspecies and a strong, but relatively divergent connection between the human and rabbit pathogens.

  1. Involving other communities through challenges and cooperation

    CERN Document Server

    Nellist, Clara; The ATLAS collaboration

    2015-01-01

    The ATLAS collaboration has recently setup three projects targeting citizen science or specific communities : The goal of the HiggsML project was to bring particle physicists and data scientists together through a challenge: compete online to obtain the best Higgs to tau tau signal significance on a set of ATLAS fully simulated signal and background. The challenge ran from May to September 2014, drawing considerable attention. In total, there were 1785 teams that participated, making it the most popular challenge at the time on the Kaggle platform. The ATLAS@home project allows volunteers to run simulations of collisions in the ATLAS detector. During the first year the community mostly consisted of software fans, who were attracted by the technical challenge and contributed greatly to the debugging through the message boards on the website. With the start of LHC, the number of people attracted for outreach reasons grew. Higgs Hunters is the first Particle Physics project hosted on the web-based citizen scienc...

  2. Development of a biomarker for Geobacter activity and strain composition; proteogenomic analysis of the citrate synthase protein during bioremediation of U(VI).

    Science.gov (United States)

    Wilkins, Michael J; Callister, Stephen J; Miletto, Marzia; Williams, Kenneth H; Nicora, Carrie D; Lovley, Derek R; Long, Philip E; Lipton, Mary S

    2011-01-01

    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.

  3. Peptide-derivatized SB105-A10 dendrimer inhibits the infectivity of R5 and X4 HIV-1 strains in primary PBMCs and cervicovaginal histocultures.

    Directory of Open Access Journals (Sweden)

    Isabella Bon

    Full Text Available Peptide dendrimers are a class of molecules that exhibit a large array of biological effects including antiviral activity. In this report, we analyzed the antiviral activity of the peptide-derivatized SB105-A10 dendrimer, which is a tetra-branched dendrimer synthetized on a lysine core, in activated peripheral blood mononuclear cells (PBMCs that were challenged with reference and wild-type human immunodeficiency virus type 1 (HIV-1 strains. SB105-A10 inhibited infections by HIV-1 X4 and R5 strains, interfering with the early phases of the viral replication cycle. SB105-A10 targets heparan sulfate proteoglycans (HSPGs and, importantly, the surface plasmon resonance (SPR assay revealed that SB105-A10 strongly binds gp41 and gp120, most likely preventing HIV-1 attachment/entry through multiple mechanisms. Interestingly, the antiviral activity of SB105-A10 was also detectable in an organ-like structure of human cervicovaginal tissue, in which SB105-A10 inhibited the HIV-1ada R5 strain infection without altering the tissue viability. These results demonstrated the strong antiviral activity of SB105-A10 and suggest a potential microbicide use of this dendrimer to prevent the heterosexual transmission of HIV-1.

  4. 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.

  5. 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, Michael J.; Callister, Stephen J.; Miletto, Marzia; Williams, Kenneth H.; Nicora, Carrie D.; Lovely, Derek R.; Long, Philip E.; Lipton, Mary S.

    2011-01-01

    Monitoring the activity of target microorganisms during stimulated bioremediation is a key problem for the development of effective remediation strategies. At the U.S. 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.

  6. Targeted tandem duplication of a large chromosomal segment in Aspergillus oryzae.

    Science.gov (United States)

    Takahashi, Tadashi; Sato, Atsushi; Ogawa, Masahiro; Hanya, Yoshiki; Oguma, Tetsuya

    2014-08-01

    We describe here the first successful construction of a targeted tandem duplication of a large chromosomal segment in Aspergillus oryzae. The targeted tandem chromosomal duplication was achieved by using strains that had a 5'-deleted pyrG upstream of the region targeted for tandem chromosomal duplication and a 3'-deleted pyrG downstream of the target region. Consequently,strains bearing a 210-kb targeted tandem chromosomal duplication near the centromeric region of chromosome 8 and strains bearing a targeted tandem chromosomal duplication of a 700-kb region of chromosome 2 were successfully constructed. The strains bearing the tandem chromosomal duplication were efficiently obtained from the regenerated protoplast of the parental strains. However, the generation of the chromosomal duplication did not depend on the introduction of double-stranded breaks(DSBs) by I-SceI. The chromosomal duplications of these strains were stably maintained after five generations of culture under nonselective conditions. The strains bearing the tandem chromosomal duplication in the 700-kb region of chromosome 2 showed highly increased protease activity in solid-state culture, indicating that the duplication of large chromosomal segments could be a useful new breeding technology and gene analysis method.

  7. Sustainable manufacturing challenges, solutions and implementation perspectives

    CERN Document Server

    Seliger, Günther; Bonvoisin, Jérémy

    2017-01-01

    Sustainability imposes an unprecedented challenge on society and has become the driving force of an urgent search for innovative solutions in all branches of economy. Manufacturing plays a key role in many areas of human living, and it is both part of the problem and of the solution. This book offers an overview of the broad field of research on sustainability in manufacturing with a particular focus on manufacturing technology and management. It summarizes the current challenges, describes best in class methods for development of sustainable manufacturing solutions and offers implementation perspectives. This volume covers areas of research such as production processes, product development, business model and corporate development, macro economy and education. The target audience primarily comprises research experts and practitioners in the field of manufacturing, but the book may also be beneficial for graduate students. .

  8. Prostate magnetic resonance imaging: challenges of implementation.

    Science.gov (United States)

    Loch, Ronald; Fowler, Kathryn; Schmidt, Ryan; Ippolito, Joseph; Siegel, Cary; Narra, Vamsi

    2015-01-01

    Prostate cancer is among the most common causes of cancer and cancer deaths in men. Screening methods and optimal treatments have become controversial in recent years. Prostate magnetic resonance imaging (MRI) is gaining popularity as a tool to assist diagnosis, risk assessment, and staging. However, implementation into clinical practice can be difficult, with many challenges associated with image acquisition, postprocessing, interpretation, reporting, and radiologic-pathologic correlation. Although state-of-the-art technology is available at select sites for targeting tissue biopsy and interpreting multiparametric prostate MRI, many institutions struggle with adapting this new technology into an efficient multidisciplinary model of patient care. This article reviews several of the challenges that radiologists should be aware of when integrating prostate MRI into their clinical practice.

  9. Proteomics Technologies and Challenges

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Proteomics is the study of proteins and their interactions in a cell. With the completion of the Human Genome Project, the emphasis is shifting to the protein compliment of the human organism. Because proteome reflects more accurately on the dynamic state of a cell, tissue, or organism, much is expected from proteomics to yield better disease markers for diagnosis and therapy monitoring. The advent of proteomics technologies for global detection and quantitation of proteins creates new opportunities and challenges for those seeking to gain greater understanding of diseases. High-throughput proteomics technologies combining with advanced bioinformatics are extensively used to identify molecular signatures of diseases based on protein pathways and signaling cascades. Mass spectrometry plays a vital role in proteomics and has become an indispensable tool for molecular and cellular biology. While the potential is great, many challenges and issues remain to be solved, such as mining low abundant proteins and integration of proteomics with genomics and metabolomics data. Nevertheless, proteomics is the foundation for constructing and extracting useful knowledge to biomedical research. In this review, a snapshot of contemporary issues in proteomics technologies is discussed.

  10. ATLAS Data Challenge 1

    CERN Document Server

    Poulard, G

    2003-01-01

    In 2002 the ATLAS experiment started a series of Data Challenges (DC) of which the 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 (HLT) and physics communities, and the production of those samples as a world-wide distributed activity. The first phase of DC1 was run during summer 2002, and involved 39 institutes in 18 countries. More than 10 million physics events and 30 million single particle events were fully simulated. Over a period of about 40 calendar days 71000 CPU-days were used producing 30 Tbytes of data in about 35000 partitions. In the second phase the next processing step was performed with the participation of 56 institutes in 21 countries (~ 4000 processors used in parallel). The basic elements of ...

  11. Safeguards by Design Challenge

    Energy Technology Data Exchange (ETDEWEB)

    Alwin, Jennifer Louise [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-09-13

    The International Atomic Energy Agency (IAEA) defines Safeguards as a system of inspection and verification of the peaceful uses of nuclear materials as part of the Nuclear Nonproliferation Treaty. IAEA oversees safeguards worldwide. Safeguards by Design (SBD) involves incorporation of safeguards technologies, techniques, and instrumentation during the design phase of a facility, rather that after the fact. Design challenge goals are the following: Design a system of safeguards technologies, techniques, and instrumentation for inspection and verification of the peaceful uses of nuclear materials. Cost should be minimized to work with the IAEA’s limited budget. Dose to workers should always be as low are reasonably achievable (ALARA). Time is of the essence in operating facilities and flow of material should not be interrupted significantly. Proprietary process information in facilities may need to be protected, thus the amount of information obtained by inspectors should be the minimum required to achieve the measurement goal. Then three different design challenges are detailed: Plutonium Waste Item Measurement System, Marine-based Modular Reactor, and Floating Nuclear Power Plant (FNPP).

  12. Résultats challenge

    CERN Multimedia

    Club de pétanque

    2015-01-01

    C'est avec un temps magnifique que se disputait pour la deuxième année le Challenge de notre cher ami Patrick DURAND le jeudi 30 juillet 2015. Vingt-six personnes formées en doublettes s'affrontaient pour trois parties .Après des parties très serrées le juge arbitre Claude JOUVE épaulé par Alain PHILIPONA déclarait  vainqueur l'imbattable Claude MACARI suivi de très près par Eric DARMEDRU et à la troisième place Christian JOUVE. La première féminine était Mireille ROCHE. La soirée se clôturait par une succulente paëlla préparée par Jennifer et sa maman Sylvie JOUVE. Rendez-vous à tous pour le jeudi 27 août 2015 pour le challenge Jean-Claude FROT Nos concours sont ouverts à tous les amateurs de pétanque.

  13. Challenge Based Innovation gala

    CERN Document Server

    CERN. Geneva; Utriainen, Tuuli Maria; Toivonen, Harri; Nordberg, Markus

    2014-01-01

    Challenge Based Innovation gala   There’s a new experiment starting in CERN called IdeaLab where we work together with detector R&D researchers to help them to bridge their knowledge into a more human, societally oriented context. Currently we are located in B153, but will move our activities to a new facility next to the Globe in May 2014. One of our first pilot projects is a 5 month course CBI (Challenge Based Innovation) where two multidisciplinary student teams join forces with Edusafe & TALENT projects at CERN. Their goal is to discover what kind of tools for learning could be created in collaboration with the two groups. After months of user interviews and low resolution prototyping they are ready to share the results with us in the form of an afternoon gala. We warmly welcome you to join us to see the students' results and experience the prototypes they have conceived. The event is in three parts, you are welcome to visit all of them,...

  14. Rising to the Challenge

    Directory of Open Access Journals (Sweden)

    Xiaoping Li

    2015-06-01

    Full Text Available Writing is recognized as a vital skill in education and the workplace; students in the United States finishing K-12 schooling are expected to be competent writers. Yet, the Nation’s Report Card found that U.S. high school graduates coming into the workforce are particularly deficient in writing skills. Teachers serve as a crucial link in the move to improve literacy skills of K-12 students; however, teachers themselves are underprepared to be writers and writing teachers. Therefore, there is an urgent need to improve teachers’ writing skills and skills of teaching writing to improve K-12 students’ writing skills in the United States. This qualitative study examined the process-based writing project experienced by 22 practicing teachers through their reflective practices in a graduate capstone class. In particular, this study explored the challenges the teachers faced and the lessons they learned through the recursive phases of writing: planning, drafting, revising, editing, conferring, and publishing. The triangulation of the researchers’ field notes, teachers’ daily reflections, and informal interviews between the instructor and the teachers indicated that the challenges the teachers faced and the lesson they learned through the process-based writing project were phase specific. On the completion of the writing project, the participating teachers (a developed a deep understanding of process-based writing; (b learned new skills of planning, drafting, revising, editing, and sharing; and (c were more confident as writers themselves and as writing teachers for their students.

  15. Review - China's Environmental Challenges

    Directory of Open Access Journals (Sweden)

    Bill Bleisch

    2013-12-01

    Full Text Available Review of: Judith Shapiro. 2012. China's Environmental Challenges. Cambridge: UK and Malden, MA: Polity Press. Judith Shapiro's latest ambitious work picks up the story of modern China's checkered relationship with the environment at approximately the point where her previous study, Mao's War Against Nature (2001, left off. This latest book sets out to address questions of grave importance to China and to the world. The litany of challenges – poisonous water and toxic air, scarcity of water and other resources, deforestation, soil erosion, loss of biodiversity – seem nearly insurmountable, despite evidence of considerable attention from the Chinese government and from China's public, and despite the rocket-like rise of China's economic power and political influence in the world. Shapiro adds to this list the growing problems with lapses in environmental justice, both within China and passed on to its neighbours and to the countries with which it trades. Not only do growing environmental problems affect China's ability to achieve the government's stated goals of a 'harmonious society' with 'moderate prosperity for all,' but these problems, and the ways that ...

  16. The ALICE Data Challenges

    Institute of Scientific and Technical Information of China (English)

    J.P.Baud; W.Carena; 等

    2001-01-01

    Since 1998,the ALICE experiment and the CERN/IT division have jointly executed several large-scale high throughput distributed computing exercises:the ALICE data challenges.The goals of these regular exercises are to test hardware and software components of the data acqusition and computing systems in realistic conditions and to execute an early integration of the overall ALICE computing infrastructure.This paper reports on the third ALICE Data Challenge (ADC III) that has been performed at CERN from January to March 2001.The data used during the ADC Ⅲ are simulated physics raw data of the ALICE TPC,produced with the ALICE simulation program AliRoot.The data acquisition was based on the ALICE online framework called the ALICE Data Acquisition Test Environment (DATE) system.The data after event building,were then formatted with the ROOT I/O package and a data catalogue based on MySQl was established.The Mass Storage System used during ADC III is CASTOR.Different software tools have been used to monitor the performances,DATE has demonstrated performances of more than 500 MByte/s.An aggregate data throughput of 85 MByte/s was sutained in CASTOR over several days.The total collected data amounts to 100 TBytes in 100.00 files.

  17. 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.

  18. 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.

  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. 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

    Directory of Open Access Journals (Sweden)

    Marcelo Weiss

    2010-01-01

    Full Text Available 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 heifers was vaccinated with SV265gE- (0,2mL containing 10(6.9TCID50 in the vulva submucosa (group IV; four heifers were vaccinated intramuscularly (group IM, 1mL containing 10(7.6TCID50 and four heifers remained as non-vaccinated controls. Heifers vaccinated IV developed mild, transient local edema and hyperemia and shed low amounts of virus for a few days after vaccination, yet a sentinel heifer maintained in close contact did not seroconvert. Attempts to reactivate the vaccine virus in two IV vaccinated heifers by intravenous administration of dexamethasone (0.5mg/kg at day 70 pv failed since no virus shedding, recrudescence of genital signs or seroconversion were observed. At day 70 pv, all vaccinated and control heifers were challenged by genital inoculation of a highly virulent BoHV-1.2 isolate (SV56/90, 10(7.1TCID50/animal. After challenge, virus shedding was detected in genital secretions of control animals for 8.2 days (8-9; in the IM group for 6.2 days (4-8 days and during 5.2 days (5-6 days in the IV group. Control non-vaccinated heifers developed moderate (2/4 or severe (2/4 vulvovaginitis lasting 9 to 13 days (x: 10.7 days. The disease was characterized by vulvar edema, vulvo-vestibular congestion, vesicles progressing to coalescence and erosions, fibrino-necrotic plaques and fibrinopurulent exudate. IM vaccinated heifers developed mild (1/3 or moderate (3/4 genital lesions, lasting 10 to 12 days (x: 10.7 days; and IV vaccinated heifers developed

  1. Achieving efficient RNAi therapy: progress and challenges

    Directory of Open Access Journals (Sweden)

    Kun Gao

    2013-07-01

    Full Text Available RNA interference (RNAi has been harnessed to produce a new class of drugs for treatment of various diseases. This review summarizes the most important parameters that govern the silencing efficiency and duration of the RNAi effect such as small interfering RNA (siRNA stability and modification, the type of delivery system and particle sizing methods. It also discusses the predominant barriers for siRNA delivery, such as off-target effects and introduces internalization, endosomal escape and mathematical modeling in RNAi therapy and combinatorial RNAi. At present, effective delivery of RNAi therapeutics in vivo remains a challenge although significant progress has been made in this field.

  2. Challenges in the miRNA research

    DEFF Research Database (Denmark)

    Singh, Tiratha Raj; Gupta, Arun; Suravajhala, Prashanth

    2013-01-01

    RNAs from their progenitor messenger RNAs (mRNAs) have arisen. Furthermore, the miRNAs are known to have synergism involving regulation of their condition-specific target genes (mRNAs). In this review, we provide a bioinformatics approach of the miRNAs and their challenges with respect to annotation......While it is known that the human genes are regulated by microRNAs (miRNAs), recent links with cancer and other diseases have widely caught interest. With several bioinformatics platforms and approaches on rise that has led to discovery of human miRNAs, validation and need for understanding mi...

  3. The challenge of conducting gambling research

    Science.gov (United States)

    2016-01-01

    Summary Responding to the survey of 5580 college students in South India in the study of George et al, the author discusses the universality of addictive gambling and its stereotyped nature. This study, together with work in North America and elsewhere, argues for more research that targets prevalence, risk factors, course, and treatment. The author points out the challenge of conducting research when funding is hard to obtain. Declaration of interests None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

  4. Offshore northern Europe, the challenges

    Energy Technology Data Exchange (ETDEWEB)

    Bergseth, S. [Statoil, Stavenger (Norway)

    1996-12-31

    This paper relates to challenges of the offshore activity in the North Sea. It is appropriate to address these challenges in the context of generating values through efficient management of resources, markets, safety and technology, as the challenges lie therein. The petroleum industry is built to turn natural resources into market value, assuring broad benefits to stake holders and shareholders. In the following, the challenges facing the industry the industry offshore Northern Europe is examined on this background

  5. Combination HIV prevention: significance, challenges, and opportunities.

    Science.gov (United States)

    Kurth, Ann E; Celum, Connie; Baeten, Jared M; Vermund, Sten H; Wasserheit, Judith N

    2011-03-01

    No single HIV prevention strategy will be sufficient to control the HIV pandemic. However, a growing number of interventions have shown promise in partially protecting against HIV transmission and acquisition, including knowledge of HIV serostatus, behavioral risk reduction, condoms, male circumcision, needle exchange, treatment of curable sexually transmitted infections, and use of systemic and topical antiretroviral medications by both HIV-infected and uninfected persons. Designing the optimal package of interventions that matches the epidemiologic profile of a target population, delivering that package at the population level, and evaluating safety, acceptability, coverage, and effectiveness, all involve methodological challenges. Nonetheless, there is an unprecedented opportunity to develop "prevention packages" that combine various arrays of evidence-based strategies, tailored to the needs of diverse subgroups and targeted to achieve high coverage for a measurable reduction in population-level HIV transmission. HIV prevention strategies that combine partially effective interventions should be scaled up and evaluated.

  6. WCET Tool Challenge 2011: Report

    DEFF Research Database (Denmark)

    Bonenfant, Armelle; Cassé, Hugues; Bünte, Sven;

    2011-01-01

    Following the successful WCET Tool Challenges in 2006 and 2008, the third event in this series was organized in 2011, again with support from the ARTIST DESIGN Network of Excellence. Following the practice established in the previous Challenges, the WCET Tool Challenge 2011 (WCC’11) defined two k...

  7. 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.

  8. Longitudinal Strain and Strain Rate Abnormalities Precede Invasive Diagnosis of Transplant Coronary Artery Vasculopathy in Pediatric Cardiac Transplant Patients.

    Science.gov (United States)

    Zoeller, Bridget B; Miyamoto, Shelley D; Younoszai, Adel K; Landeck, Bruce F

    2016-04-01

    Transplant coronary artery vasculopathy (TCAV) is the primary cause of late graft loss in pediatric heart transplant recipients. TCAV is diagnosed using angiography or intravascular ultrasound; however, noninvasive methods remain elusive. We sought to define patterns of myocardial mechanics in patients with TCAV and to determine whether this can detect TCAV before invasive methods. In this retrospective study, we queried our heart transplant database to identify all recipients with TCAV since 2006 (n = 41). Echoes were reviewed from the last normal catheterization and at TCAV diagnosis, and from time-matched transplant controls (n = 33) without TCAV. Peak global circumferential and longitudinal strain and systolic and diastolic strain rate (SSR and DSR) of the left ventricle were derived using velocity vector imaging. T tests were used to compare both groups longitudinally and between groups at both time points. Longitudinal strain, SSR, and DSR were diminished in the TCAV group compared to the transplant control group at both time points. No differences were found across time points in either group. Retrospective modeling using a longitudinal strain cutoff of 15 % on echoes 2 years prior to TCAV diagnosis predicted development or exclusion of TCAV with sensitivity of 53 %, specificity of 89 % with an area under the curve of 0.8. Decreases in longitudinal strain measurements demonstrate that alterations in myocardial mechanics occur in patients with TCAV at least 2 years prior to invasive diagnosis. These early changes may be due to microvascular disease. This modality could aid in earlier treatment and intervention for this challenging problem .

  9. Design of the LBNF Beamline Target Station

    Energy Technology Data Exchange (ETDEWEB)

    Tariq, S. [Fermilab; Ammigan, K. [Fermilab; Anderson, K.; ; Buccellato, S. A. [Fermilab; Crowley, C. F. [Fermilab; Hartsell, B. D. [Fermilab; Hurh, P. [Fermilab; Hylen, J. [Fermilab; Kasper, P. [Fermilab; Krafczyk, G. E. [Fermilab; Lee, A. [Fermilab; Lundberg, B. [Fermilab; Reitzner, S. D. [Fermilab; Sidorov, V. [Fermilab; Stefanik, A. M. [Fermilab; Tropin, I. S. [Fermilab; Vaziri, K. [Fermilab; Williams, K. [Fermilab; Zwaska, R. M. [Fermilab; Densham, C. [RAL, Didcot

    2016-10-01

    The Long Baseline Neutrino Facility (LBNF) project will build a beamline located at Fermilab to create and aim an intense neutrino beam of appropriate energy range toward the DUNE detectors at the SURF facility in Lead, South Dakota. Neutrino production starts in the Target Station, which consists of a solid target, magnetic focusing horns, and the associated sub-systems and shielding infrastructure. Protons hit the target producing mesons which are then focused by the horns into a helium-filled decay pipe where they decay into muons and neutrinos. The target and horns are encased in actively cooled steel and concrete shielding in a chamber called the target chase. The reference design chase is filled with air, but nitrogen and helium are being evaluated as alternatives. A replaceable beam window separates the decay pipe from the target chase. The facility is designed for initial operation at 1.2 MW, with the ability to upgrade to 2.4 MW, and is taking advantage of the experience gained by operating Fermilab’s NuMI facility. We discuss here the design status, associated challenges, and ongoing R&D and physics-driven component optimization of the Target Station.

  10. Programming Native CRISPR Arrays for the Generation of Targeted Immunity

    OpenAIRE

    2016-01-01

    IMPORTANCE CRISPR-Cas systems have entered the public consciousness as genome editing tools due to their readily programmable nature. In industrial settings, natural CRISPR-Cas immunity is already exploited to generate strains resistant to potentially disruptive viruses. However, the natural process by which bacteria acquire new target specificities (adaptation) is difficult to study and manipulate. The target against which immunity is conferred is selected stochastically. By biasing the immu...

  11. Targeted tumor radiotherapy

    Directory of Open Access Journals (Sweden)

    Unak Perihan

    2002-01-01

    Full Text Available Targeted tumor radiotherapy is selectively delivery of curative doses of radiation to malignant sites. The aim of the targeted tumor radiotherapy is to use the radionuclides which have high LET particle emissions conjugated to appropriate carrier molecules. The radionuclides are selectively collected by tumor cells, depositing lethal doses to tumor cells while no admission occur to normal cells. In theory, targeted radiotherapy has several advantages over conventional radiotherapy since it allows a high radiation dose to be administered without causing normal tissue toxicity, although there are some limitations in the availability of appropriate targeting agents and in the calculations of administered doses. Therefore, for routine clinical applications more progress is still needed. In this article, the potential use of targeted tumor radiotherapy is briefly reviewed. More general aspects and considerations, such as potential radionuclides, mechanisms of tumor targeting was also outlined.

  12. Identification and nitrogen regulation of the cyanase gene from the cyanobacteria Synechocystis sp. strain PCC 6803 and Synechococcus sp. strain PCC 7942.

    OpenAIRE

    Harano, Y; Suzuki, I.; Maeda, S; Kaneko, T.; Tabata, S; Omata, T

    1997-01-01

    An open reading frame (slr0899) on the genome of Synechocystis sp. strain PCC 6803 encodes a polypeptide of 149 amino acid residues, the sequence of which is 40% identical to that of cyanase from Escherichia coli. Introduction into a cyanase-deficient E. coli strain of a plasmid-borne slr0899 resulted in expression of low but significant activity of cyanase. Targeted interruption of a homolog of slr0899 from Synechococcus sp. strain PCC 7942, encoding a protein 77% identical to that encoded b...

  13. The Global Energy Challenge

    DEFF Research Database (Denmark)

    Connolly, David

    2011-01-01

    This report gives a brief overview of the global energy challenge and subsequently outlines how and where renewable energy could be developed to solve these issues. The report does not go into a lot of detail on these issues and hence, it is meant as an overview only. The report begins by outlining...... the causes of global climate change, concluding that energy-related emissions are the primary contributors to the problem. As a result, global energy production is analysed in more detail, discussing how it has evolved over the last 30 years and also, how it is expected to evolve in the coming 30 years....... Afterwards, the security of the world’s energy supply is investigated and it becomes clear that there is both an inevitable shortage of fossil fuels and a dangerous separation of supply and demand. The final topic discussed is renewable energy, since it is one sustainable solution to the global energy...

  14. Energy Challenges for ICT

    DEFF Research Database (Denmark)

    Fagas, Giorgos; Gallagher, John Patrick; Gammaitoni, Luca

    2017-01-01

    The energy consumption from the expanding use of information and communications technology (ICT) is unsustainable with present drivers, and it will impact heavily on the future climate change. However, ICT devices have the potential to contribute significantly to the reduction of CO2 emission...... the energy sustainability of ICT and capture the full potential of ICT in resource efficiency, a multidisciplinary ICT-energy community needs to be brought together covering devices, microarchitectures, ultra large-scale integration (ULSI), high-performance computing (HPC), energy harvesting, energy storage......, system design, embedded systems, efficient electronics, static analysis, and computation. In this chapter, we introduce challenges and opportunities in this emerging field and a common framework to strive towards energy-sustainable ICT....

  15. A specific nanomanufacturing challenge

    Science.gov (United States)

    Kelly, M. J.; Dean, M. C.

    2016-03-01

    For a science to become a technology, a certain level of control has to have been established over the way items are fabricated for manufacture and use. Here we first consider the challenge of making and using a LEGO® brick scaled down by a factor of 10 n for n = 0-6 in each spatial dimension, i.e. from millimetres to nanometres. We consider both the manufacture and the subsequent properties of the nanobricks that pertain to their use in constructing and dismantling structures. As n increases, the ability to use fails first, to manufacture fails second and to fabricate fails last. Applied to the vast literature in nanoscience, this process emphasises the unmanufacturability of most nanoscale artefacts.

  16. The challenge of implementation

    DEFF Research Database (Denmark)

    Andersen, Karen Heide Hauge

    2015-01-01

    Reaching the students in innovation and entrepreneurship courses is hard, when the courses are a requirement but not included in the main project of the curriculum. It is a major paradox for lecturers, who have never participated in and cannot see the relevance of such course, to implement...... these 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 the paper: which factors influence the degree of implementation of innovation and entrepreneurship in the individual lecturers’ daily teaching? The paper questions the common approach taken by higher educational institutions whereby lecturers are urged to teach innovation and entrepreneurship with minor...

  17. EOSDIS Customer Support Challenges

    Science.gov (United States)

    Moses, J. F.; Boquist, C. L.

    2006-05-01

    The Earth Observation System Data and Information System (EOSDIS) is a large, complex data system currently supporting over 18 operational NASA satellite missions including the flagship EOS missions: Terra, Aqua, and Aura. The observations collected by these missions are kept at geographically distributed data centers. EOSDIS manages over four petabytes of data accessed by over 200,000 distinct users last year. The data centers distributed more than 37 million Earth science data products during 2005 to a diverse customer community. An important goal for these data centers is to provide an adequate service at a uniform level for the user community to ensure we get the most benefit from our investment in space resources. This paper discusses the challenges, the ways the data centers coordinate among themselves to provide service, and recent results of measuring customer satisfaction with this service.

  18. Challenges in plastics recycling

    DEFF Research Database (Denmark)

    Pivnenko, Kostyantyn; Jakobsen, L. G.; Eriksen, Marie Kampmann

    2015-01-01

    Recycling of waste plastics still remains a challenging area in the waste management sector. The current and potential goals proposed on EU or regional levels are difficult to achieve, and even to partially fullfil them the improvements in collection and sorting should be considerable. A study...... was undertaken to investigate the factors affecting quality in plastics recycling. The preliminary results showed factors primarily influencing quality of plastics recycling to be polymer cross contamination, presence of additives, non-polymer impurities, and polymer degradation. Deprivation of plastics quality......, with respect to recycling, has been shown to happen throughout the plastics value chain, but steps where improvements may happen have been preliminary identified. Example of Cr in plastic samples analysed showed potential spreading and accumulation of chemicals ending up in the waste plastics. In order...

  19. Multicore Programming Challenges

    Science.gov (United States)

    Perrone, Michael

    The computer industry is facing fundamental challenges that are driving a major change in the design of computer processors. Due to restrictions imposed by quantum physics, one historical path to higher computer processor performance - by increased clock frequency - has come to an end. Increasing clock frequency now leads to power consumption costs that are too high to justify. As a result, we have seen in recent years that the processor frequencies have peaked and are receding from their high point. At the same time, competitive market conditions are giving business advantage to those companies that can field new streaming applications, handle larger data sets, and update their models to market conditions faster. The desire for newer, faster and larger is driving continued demand for higher computer performance.

  20. Ayurveda research: Ontological challenges

    Directory of Open Access Journals (Sweden)

    Jayakrishna Nayak

    2012-01-01

    Full Text Available Collaborative research involving Ayurveda and the current sciences is undoubtedly an imperative and is emerging as an exciting horizon, particularly in basic sciences. Some work in this direction is already going on and outcomes are awaited with bated breath. For instance the ′ASIIA (A Science Initiative In Ayurveda′ projects of Dept of Science and Technology, Govt of India, which include studies such as Ayurvedic Prakriti and Genetics. Further intense and sustained collaborative research needs to overcome a subtle and fundamental challenge-the ontologic divide between Ayurveda and all the current sciences. Ontology, fundamentally, means existence; elaborated, ontology is a particular perspective of an object of existence and the vocabulary developed to share that perspective. The same object of existence is susceptible to several ontologies. Ayurveda and modern biomedical as well as other sciences belong to different ontologies, and as such, collaborative research cannot be carried out at required levels until a mutually acceptable vocabulary is developed.