Nonspecific PCR amplification by high-fidelity polymerases: implications for next-generation sequencing of AFLP markers.

High-fidelity 'proofreading' polymerases are often used in library construction for next-generation sequencing projects, in an effort to minimize errors in the resulting sequence data. The increased template fidelity of these polymerases can come at the cost of reduced template specificity, and library preparation methods based on the AFLP technique may be particularly susceptible. Here, we compare AFLP profiles generated with standard Taq and two versions of a high-fidelity polymerase. We find that Taq produces fewer and brighter peaks than high-fidelity polymerase, suggesting that Taq performs better at selectively amplifying templates that exactly match the primer sequences. Because the higher accuracy of proofreading polymerases remains important for sequencing applications, we suggest that it may be more effective to use alternative library preparation methods.

Evaluation of the user-friendliness of seven new generation intensive care ventilators.

OBJECTIVE: To explore the user-friendliness and ergonomics of seven new generation intensive care ventilators. DESIGN: Prospective task-performing study. SETTING: Intensive care research laboratory, university hospital. METHODS: Ten physicians experienced in mechanical ventilation, but without prior knowledge of the ventilators, were asked to perform eight specific tasks [turning the ventilator on; recognizing mode and parameters; recognizing and setting alarms; mode change; finding and activating the pre-oxygenation function; pressure support setting; stand-by; finding and activating non-invasive ventilation (NIV) mode]. The time needed for each task was compared to a reference time (by trained physiotherapist familiar with the devices). A time >180 s was considered a task failure. RESULTS: For each of the tests on the ventilators, all physicians' times were significantly higher than the reference time (P < 0.001). A mean of 13 +/- 8 task failures (16%) was observed by the ventilator. The most frequently failed tasks were mode and parameter recognition, starting pressure support and finding the NIV mode. Least often failed tasks were turning on the pre-oxygenation function and alarm recognition and management. Overall, there was substantial heterogeneity between machines, some exhibiting better user-friendliness than others for certain tasks, but no ventilator was clearly better that the others on all points tested. CONCLUSIONS: The present study adds to the available literature outlining the ergonomic shortcomings of mechanical ventilators. These results suggest that closer ties between end-users and manufacturers should be promoted, at an early development phase of these machines, based on the scientific evaluation of the cognitive processes involved by users in the clinical setting.

Generation mean analysis in relation to polygenic systems with epistasis and fixed genes

Epistatic effects involving genic combinations of fixed and non fixed genes are shown to contribute to the genotypic mean of any population. These effects define specific additive x additive and additive x dominant epistatic components. As such components are not estimable, their relative importance cannot be assessed. These epistatic effects can cause bias in the estimates of the additive and dominance components to which they are confounded. The magnitude of the bias depends on the relative values of the epistatic effects, comparatively to deviations d and h, type of prevailing epistasis and direction of dominance.

Consumer Advisory:Student Loan “Rescue” Companies Are No Lifeline! July 2014

The Attorney General’s Consumer Protection Division receives hundreds of calls and consumer complaints every year. Follow these tips to avoid unexpected expense and disappointments. This record is about:Student Loan “Rescue” Companies Are No Lifeline!

Generation of biological association networks: A novel strategy to detect new targets in cancer therapy

The aim of this work was to design a novel strategy to detect new targets for anticancer treatments. The rationale was to build Biological Association Networks from differentially expressed genes in drug-resistant cells to identify important nodes within the Networks. These nodes may represent putative targets to attack in cancer therapy, as a way to destabilize the gene network developed by the resistant cells to escape from the drug pressure. As a model we used cells resistant to methotrexate (MTX), an inhibitor of DHFR. Selected node-genes were analyzed at the transcriptional level and from a genotypic point of view. In colon cancer cells, DHFR, the AKR1 family, PKC¿, S100A4, DKK1, and CAV1 were overexpressed while E-cadherin was lost. In breast cancer cells, the UGT1A family was overexpressed, whereas EEF1A1 was overexpressed in pancreatic cells. Interference RNAs directed against these targets sensitized cells towards MTX.

Herbivory in the previous generation primes plants for enhanced insect resistance.

Inducible defenses, which provide enhanced resistance after initial attack, are nearly universal in plants. This defense signaling cascade is mediated by the synthesis, movement, and perception of jasmonic acid and related plant metabolites. To characterize the long-term persistence of plant immunity, we challenged Arabidopsis (Arabidopsis thaliana) and tomato (Solanum lycopersicum) with caterpillar herbivory, application of methyl jasmonate, or mechanical damage during vegetative growth and assessed plant resistance in subsequent generations. Here, we show that induced resistance was associated with transgenerational priming of jasmonic acid-dependent defense responses in both species, caused caterpillars to grow up to 50% smaller than on control plants, and persisted for two generations in Arabidopsis. Arabidopsis mutants that are deficient in jasmonate perception (coronatine insensitive1) or in the biogenesis of small interfering RNA (dicer-like2 dicer-like3 dicer-like4 and nuclear RNA polymerase d2a nuclear RNA polymerase d2b) do not exhibit inherited resistance. The observation of inherited resistance in both the Brassicaceae and Solanaceae suggests that this trait may be more widely distributed in plants. Epigenetic resistance to herbivory thus represents a phenotypically plastic mechanism for enhanced defense across generations.

"Next-generation" Sequencing (NGS): The new genomic revolution

In the past 5 years "Next-generation" Sequencing (NGS) technologies have transformed genomics by delivering fast, inexpensive and accurate genomeinformation changing the way we think about scientific approaches in basic,applied and clinical research. The inexpensive production of large volumes ofsequence data is the main advantage over the automated Sanger method,making this new technology useful for many applications. In this chapter, a brieftechnical review of NGS technologies is given, along with the keys to NGSsuccess and a broad range of applications for NGS technologies.

La Generation Sandwich en Suisse Romande: mieux comprendre les facteurs associés avec la santé perçue afin de mieux agir en promotion de la santé [Sandwich Generation in Roman Switzerland : a better understanding of factors linked with perceived health for better acting in health promotion].

The so-called < Sandwich Generation > (SG) is characterized by concurrent and competing professional, familial, and informal caregiving workloads. These stressors pose potential health risks. However, the current knowledge about SG characteristics and perceived state of health are insufficient to allow occupational health nurses to develop evidence-based interventions designed for health promotion. We aimed to describe this population and examine the relationships between these coexisting workloads and their perceived health. This study is based on a descriptive, correlational design. Employees of a Swiss public administration completed an electronic questionnaire. Of 844 respondents, 23 % are SG members. Ages of frailed parents or parents-in-law, co-residence with the latters, children still living at home predict that employees could be members of the SG. Perceived physical health status of SG members is rated better than mental health status. The heterogeneity of SG is reflected in three clusters. Finally, physical health score is the only that differs from the other health scores adjusting for clusters and sex. This study provides a foundation for developing preventive interventions targeting the SG.

Circulating miRNAs: a new generation of anti-doping biomarkers

MicroRNAs (miRNAs) are small non-coding RNAs that regulate a variety of biological processes. Cell-free miRNAs detected in blood plasma are used as specific and sensitive markers of physiological processes and some diseases. Circulating miRNAs are highly stable in body fluids, for example plasma. Therefore, profiles of circulating miRNAs have been investigated for potential use as novel, non-invasive anti-doping biomarkers. This review describes the biological mechanisms underlying the variation of circulating miRNAs, revealing that they have great potential as a new class of biomarker for detection of doping substances. The latest developments in extraction and profiling technology, and the technical design of experiments useful for anti-doping, are also discussed. Longitudinal measurements of circulating miRNAs in the context of the athlete biological passport are proposed as an efficient strategy for the use of these new markers. The review also emphasizes potential challenges for the translation of circulating miRNAs from research into practical anti-doping applications.

Learning form Nature to improve the heat generation of iron-oxide nanoparticles for magnetic hyperthermia applications.

The performance of magnetic nanoparticles is intimately entwined with their structure, mean size and magnetic anisotropy. Besides, ensembles offer a unique way of engineering the magnetic response by modifying the strength of the dipolar interactions between particles. Here we report on an experimental and theoretical analysis of magnetic hyperthermia, a rapidly developing technique in medical research and oncology. Experimentally, we demonstrate that single-domain cubic iron oxide particles resembling bacterial magnetosomes have superior magnetic heating efficiency compared to spherical particles of similar sizes. Monte Carlo simulations at the atomic level corroborate the larger anisotropy of the cubic particles in comparison with the spherical ones, thus evidencing the beneficial role of surface anisotropy in the improved heating power. Moreover we establish a quantitative link between the particle assembling, the interactions and the heating properties. This knowledge opens new perspectives for improved hyperthermia, an alternative to conventional cancer therapies.

Evolutionarily stable learning schedules and cumulative culture in discrete generation models.

Individual learning (e.g., trial-and-error) and social learning (e.g., imitation) are alternative ways of acquiring and expressing the appropriate phenotype in an environment. The optimal choice between using individual learning and/or social learning may be dictated by the life-stage or age of an organism. Of special interest is a learning schedule in which social learning precedes individual learning, because such a schedule is apparently a necessary condition for cumulative culture. Assuming two obligatory learning stages per discrete generation, we obtain the evolutionarily stable learning schedules for the three situations where the environment is constant, fluctuates between generations, or fluctuates within generations. During each learning stage, we assume that an organism may target the optimal phenotype in the current environment by individual learning, and/or the mature phenotype of the previous generation by oblique social learning. In the absence of exogenous costs to learning, the evolutionarily stable learning schedules are predicted to be either pure social learning followed by pure individual learning ("bang-bang" control) or pure individual learning at both stages ("flat" control). Moreover, we find for each situation that the evolutionarily stable learning schedule is also the one that optimizes the learned phenotype at equilibrium.

Generation and nonlinear evolution of shore-oblique/transverse sand bars

The coupling between topography, waves and currents in the surf zone may selforganize to produce the formation of shore-transverse or shore-oblique sand bars on an otherwise alongshore uniform beach. In the absence of shore-parallel bars, this has been shown by previous studies of linear stability analysis, but is now extended to the finite-amplitude regime. To this end, a nonlinear model coupling wave transformation and breaking, a shallow-water equations solver, sediment transport and bed updating is developed. The sediment flux consists of a stirring factor multiplied by the depthaveraged current plus a downslope correction. It is found that the cross-shore profile of the ratio of stirring factor to water depth together with the wave incidence angle primarily determine the shape and the type of bars, either transverse or oblique to the shore. In the latter case, they can open an acute angle against the current (upcurrent oriented) or with the current (down-current oriented). At the initial stages of development, both the intensity of the instability which is responsible for the formation of the bars and the damping due to downslope transport grow at a similar rate with bar amplitude, the former being somewhat stronger. As bars keep on growing, their finite-amplitude shape either enhances downslope transport or weakens the instability mechanism so that an equilibrium between both opposing tendencies occurs, leading to a final saturated amplitude. The overall shape of the saturated bars in plan view is similar to that of the small-amplitude ones. However, the final spacings may be up to a factor of 2 larger and final celerities can also be about a factor of 2 smaller or larger. In the case of alongshore migrating bars, the asymmetry of the longshore sections, the lee being steeper than the stoss, is well reproduced. Complex dynamics with merging and splitting of individual bars sometimes occur. Finally, in the case of shore-normal incidence the rip currents in the troughs between the bars are jet-like while the onshore return flow is wider and weaker as is observed in nature.

Generation of symmetric periodic orbits by a heteroclinic loop formed by two singular points and their invariant manifolds of dimension 1 and 2 in R3

In this paper we will find a continuous of periodic orbits passing near infinity for a class of polynomial vector fields in R3. We consider polynomial vector fields that are invariant under a symmetry with respect to a plane and that possess a “generalized heteroclinic loop” formed by two singular points e+ and e− at infinity and their invariant manifolds � and . � is an invariant manifold of dimension 1 formed by an orbit going from e− to e+, � is contained in R3 and is transversal to . is an invariant manifold of dimension 2 at infinity. In fact, is the 2–dimensional sphere at infinity in the Poincar´e compactification minus the singular points e+ and e−. The main tool for proving the existence of such periodic orbits is the construction of a Poincar´e map along the generalized heteroclinic loop together with the symmetry with respect to .