An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes

Parasitic nematodes infect hundreds of millions of people and farmed livestock. Further, plant parasitic nematodes result in major crop damage. The pipeline of therapeutic compounds is limited and parasite resistance to the existing anthelmintic compounds is a global threat. We have developed an INVertebrate Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical screening, and an algorithm (Paragon) which allows screening for compounds that have an effect on motility and development of parasitic worms. We have validated its utility by determining the efficacy of a panel of known anthelmintics against model and parasitic nematodes: Caenorhabditis elegans, Haemonchus contortus, Teladorsagia circumcincta, and Trichuris muris. We then applied the system to screen the Pathogen Box chemical library in a blinded fashion and identified compounds already known to have anthelmintic or anti-parasitic activity, including tolfenpyrad, auranofin, and mebendazole; and 14 compounds previously undescribed as anthelmintics, including benzoxaborole and isoxazole chemotypes. This system offers an effective, high-throughput system for the discovery of novel anthelmintics

Experimental analysis of gas to water two phase closed thermosyphon based heat exchanger

Paper presented to the 10th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Florida, 14-16 July 2014.Wickless heat pipes have been attracting increased attention in the last two decades due to their reliability and high heat transfer potential per unit area. Their most common application is in the process industry, when coupled to waste heat recovery devices. Heat pipe based heat exchangers offer many advantages when compared with conventional waste heat recovery systems; advantages that are detailed in the current work. The design of such devices, however, is not a straightforward process due to the complex modes of heat transfer mechanisms involved. In this paper, the characterisation of a cross-flow heat pipe based heat exchanger is studied experimentally, using correlations currently available in literature. A design tool with the purpose of predicting the performance of the test unit was also developed and validated through comparison with the experimental results. The design tool was validated with the use of a purpose-built experimental facility.cf201

Multilayered feed forward Artificial Neural Network model to predict the average summer-monsoon rainfall in India

In the present research, possibility of predicting average summer-monsoon rainfall over India has been analyzed through Artificial Neural Network models. In formulating the Artificial Neural Network based predictive model, three layered networks have been constructed with sigmoid non-linearity. The models under study are different in the number of hidden neurons. After a thorough training and test procedure, neural net with three nodes in the hidden layer is found to be the best predictive model.Comment: 19 pages, 1 table, 3 figure

Aperiodicity in one-way Markov cycles and repeat times of large earthquakes in faults

A common use of Markov Chains is the simulation of the seismic cycle in a fault, i.e. as a renewal model for the repetition of its characteristic earthquakes. This representation is consistent with Reid's elastic rebound theory. Here it is proved that in {\it any} one-way Markov cycle, the aperiodicity of the corresponding distribution of cycle lengths is always lower than one. This fact concurs with observations of large earthquakes in faults all over the world

A new approach to estimating hazard posed by debris flows in the Westfjords of Iceland

The aim of this study is to improve the assessment of hazard posed by debris flows to the people and settlements of northwest Iceland by studying very recent examples from above the town of Ísafjörður and other nearby localities. Debris flows are a recognised hazard in the region: above Ísafjörður, they occur with particularly high frequency and have appreciable volumes (up to 14 000 m3). We have used airborne laser altimeter (LiDAR) and differential Global Positioning System (GPS) data to produce isopach maps of flows that occurred in 1999, 2007, and 2008. Our data show that these flows begin depositing at higher slope gradients and are also more mobile than hillslope debris flows reported by other authors. Above a 19° slope, erosion is initiated independent of the distance along the flowpath. Using the isopach maps and associated field observations, we have found a relationship between ground slope and patterns in deposition volume. We have used this finding as a basis for an empirical model that enables an estimate of the total travel distance and final thickness of future debris flows to be calculated. This has enabled us to identify areas of the town which are at risk; some of these are not obvious without this analysis. This model is notable for its simplicity, which allows future debris flow characteristics to be predicted without the need to determine the precise fluid dynamic parameters of the flow such as viscosity and velocity, which are required to implement more complex models

Complex relationships among personality traits, job characteristics, and work behaviors

The aim of the study was to investigate the additive, mediating, and moderating effects of personality traits and job characteristics on work behaviors. Job applicants (N = 161) completed personality questionnaires measuring extraversion, neuroticism, achievement motivation, and experience seeking. One and a half years later, supervisors rated the applicants' job performance, and the job incumbents completed questionnaires about skill variety, autonomy, and feedback, work stress, job satisfaction, work self-efficacy, and propensity to leave. LISREL was used to test 15 hypotheses. Perceived feedback mediated the relationship between achievement motivation and job performance. Extraversion predicted work self-efficacy and job satisfaction. Work stress mediated the relationship between neuroticism and job satisfaction. Job satisfaction and experience seeking were related to propensity to leave. Autonomy, skill variety, and feedback were related to job satisfaction

Enhanced glycemic control with combination therapy for type 2 diabetes in primary care

Type 2 diabetes mellitus is an increasingly common medical problem for primary care clinicians to address. Treatment of diabetes has evolved from simple replacement of insulin (directly or through insulin secretagogs) through capture of mechanisms such as insulin sensitizers, alpha-glucosidase inhibitors, and incretins. Only very recently has recognition of the critical role of the gastrointestinal system as a major culprit in glucose dysregulation been established. Since glycated hemoglobin A1c reductions provide meaningful risk reduction as well as improved quality of life, it is worthwhile to explore evolving paths for more efficient use of the currently available pharmacotherapies. Because diabetes is a progressive disease, even transiently successful treatment will likely require augmentation as the disorder progresses. Pharmacotherapies with complementary mechanisms of action will be necessary to achieve glycemic goals. Hence, clinicians need to be well informed about the various noninsulin alternatives that have been shown to be successful in glycemic goal attainment. This article reviews the benefits of glucose control, the current status of diabetes control, pertinent pathophysiology, available pharmacological classes for combination, limitations of current therapies, and suggestions for appropriate combination therapies, including specific suggestions for thresholds at which different strategies might be most effectively utilized by primary care clinicians

Observation of hard scattering in photoproduction events with a large rapidity gap at HERA

Events with a large rapidity gap and total transverse energy greater than 5 GeV have been observed in quasi-real photoproduction at HERA with the ZEUS detector. The distribution of these events as a function of the $\gamma p$ centre of mass energy is consistent with diffractive scattering. For total transverse energies above 12 GeV, the hadronic final states show predominantly a two-jet structure with each jet having a transverse energy greater than 4 GeV. For the two-jet events, little energy flow is found outside the jets. This observation is consistent with the hard scattering of a quasi-real photon with a colourless object in the proton.Comment: 19 pages, latex, 4 figures appended as uuencoded fil

Lichenometric dating (lichenometry) and the biology of the lichen genus rhizocarpon:challenges and future directions

Lichenometric dating (lichenometry) involves the use of lichen measurements to estimate the age of exposure of various substrata. Because of low radial growth rates and considerable longevity, species of the crustose lichen genus Rhizocarpon have been the most useful in lichenometry. The primary assumption of lichenometry is that colonization, growth and mortality of Rhizocarpon are similar on surfaces of known and unknown age so that the largest thalli present on the respective faces are of comparable age. This review describes the current state of knowledge regarding the biology of Rhizocarpon and considers two main questions: (1) to what extent does existing knowledge support this assumption; and (2) what further biological observations would be useful both to test its validity and to improve the accuracy of lichenometric dates? A review of the Rhizocarpon literature identified gaps in knowledge regarding early development, the growth rate/size curve, mortality, regeneration, competitive effects, colonization, and succession on rock surfaces. The data suggest that these processes may not be comparable on different rock surfaces, especially in regions where growth rates and thallus turnover are high. In addition, several variables could differ between rock surfaces and influence maximum thallus size, including rate and timing of colonization, radial growth rates, environmental differences, thallus fusion, allelopathy, thallus mortality, colonization and competition. Comparative measurements of these variables on surfaces of known and unknown age may help to determine whether the basic assumptions of lichenometry are valid. Ultimately, it may be possible to take these differences into account when interpreting estimated dates