Drug target validation and identification of secondary drug target effects using DNA microarrays

We describe here a method for drug target validation and identification of secondary drug target effects based on genome-wide gene expression patterns. The method is demonstrated by several experiments, including treatment of yeast mutant strains defective in calcineurin, immunophilins or other genes with the immunosuppressants cyclosporin A or FK506. Presence or absence of the characteristic drug 'signature' pattern of altered gene expression in drug-treated cells with a mutation in the gene encoding a putative target established whether that target was required to generate the drug signature. Drug dependent effects were seen in 'targetless' cells, showing that FK506 affects additional pathways independent of calcineurin and the immunophilins. The described method permits the direct confirmation of drug targets and recognition of drug-dependent changes in gene expression that are modulated through pathways distinct from the drug's intended target. Such a method may prove useful in improving the efficiency of drug development programs.     

Persistence at source of Listeria spp. in raw milk

From 36 of 315 bulk tank sources of raw milk found to harbour Listeria spp., 34 were available for resampling at intervals to determine persistence of the organisms. Listeriae were reisolated from 21 sources. In 16 Listeria spp. were isolated in one retest. From the other five listeriae were obtained in more than one retest. Listerial populations were not particularly persistent. In all but one instance listeriae were not reisolated more than 5 months after initial sampling. Intermittent variations in Listeria spp. isolated were observed. Some repeat samples yielded the same species as originally identified, but sometimes only one of originally two species was isolated. On occasions completely different or additional species were found. The aetiology of listeriosis in cattle and contamination of raw milk is discussed.     

Effect of specific surface area on capacitance in asymmetric carbon/α-MnO2 supercapacitors

α-MnO₂ has been made using a solid state synthesis and the specific surface area then modified through milling. The formation of α-MnO₂ (specific surface area 96 m² g⁻¹) has been studied by SEM and powder XRD prior to milling. Electrode films (cast using MnO₂, graphite and PVDF) have been investigated using N₂ sorption at 77 K and show a more complex relationship than their parent oxides. Specific capacitances of 235 F g⁻¹ were observed in cyclic voltammetry studies in (NH₄)₂SO₄ (aq.) electrolyte. Good cyclability was observed in hybrid C/MnO₂ cells investigated through both galvanostatic and electrochemical impedance techniques. The specific capacitances of the cells were found to correlate with S_BET of the electrode films and not that of the parent MnO₂ powders.     

Introduction to the special issue

Artificial intelligence is a productive research paradigm for a variety of problems that arise in the world of investments This article provides an introduction to this special issue of Applied Artificial Intelligence - Artificial Intelligence Applications on Wall Street - which is devoted to financial AI applications The articles in this volume are derived from papers presented at the Third International Conference on Artificial Intelligence Applications on Wall Street held in June 1995 in New York City     

Survival and metamorphosis of low-density populations of larval sea lampreys (Petromyzon marinus) in streams following lampricide treatment

Sea lamprey Petromyzon marinus control in the Great Lakes primarily involves application of lampricides to streams where larval production occurs to kill larvae prior to their metamorphosing and entering the lakes as parasites (juveniles). Because lampricides are not 100% effective, larvae that survive treatment may metamorphose before streams are again treated. Larvae that survive treatment have not been widely studied, so their dynamics are not well understood. We tagged and released larvae in six Great Lake tributaries following lampricide treatment and estimated vital demographic rates using multistate tag-recovery models. Model-averaged larval survivals ranged from 56.8 to 57.6%. Model-averaged adult recovery rates, which were the product of juvenile survivals and adult capture probabilities, ranged from 6.8 to 9.3%. Using stochastic simulations, we estimated production of juvenile sea lampreys from a hypothetical population of treatment survivors under different growth conditions based on parameter estimates from this research. For fast-growing populations, juvenile production peaked 2 years after treatment. For slow-growing populations, juvenile production was approximately one-third that of fast-growing populations, with production not peaking until 4 years after treatment. Our results suggest that dynamics (i.e., survival, metamorphosis) of residual larval populations are very similar to those of untreated larval populations. Consequently, residual populations do not necessarily warrant special consideration for the purpose of sea lamprey control and can be ranked for treatment along with other populations. Consecutive lampricide treatments, which are under evaluation by the sea lamprey control program, would be most effective for reducing juvenile production in large, fast-growing populations.     

Measuring maximum specific growth rate and half saturation coefficient for activated sludge systems using a freeze concentration technique

To measure the maximum specific growth rate (μ_max) and the half saturation coefficient (K_s), a simple respirometric technique was used, where differing volumes of concentrated wastewater were contacted with biomass in a respirometer and the response measured as a change in oxygen uptake rate (ΔOUR). The ΔOUR was then related to the growth rate, and a series of substrate concentration/growth rate relationships determined from which μ_max and K_s were calculated. A freeze concentration technique was developed to concentrate the wastewater. The concentration technique did not alter the response of the microorganisms to the wastewater. Maximum specific growth rates (μ_max) and half saturation coefficients (K_s) were found to vary between 1.3 and 1.9 d⁻¹ and 1.5 and 3.2 mg l⁻¹, respectively.     

Durable effects of implementation intentions: Reduced rates of confirmed pregnancy at 2 years.

Objective: To assess the long-term impact of implementation intention formation in reducing consultations for emergency contraception and pregnancy testing among teenage women. Design: Teenage women visiting a family planning clinic were randomly assigned to implementation intention versus control conditions. Main outcome measures: Objective measures of consultation outcomes were obtained from clinic records at 2-year follow-up (N = 227). Results: Rates of consultation for emergency contraception and pregnancy testing in the implementation intentions condition were 19% and 33% lower, respectively, compared to the rates observed in the control condition. Pregnancy rates were 43% lower. Intervention participants who consulted for emergency contraception and pregnancy testing at baseline were more than twice as likely to change to consulting for contraceptive supplies over the follow-up period compared to equivalent control participants (19% vs. 9%). Conclusion: The impact of implementation intention formation on reducing pregnancy risk among teenagers is durable over 2 years. Implementation intentions were successful in changing behavior among precisely those participants who were at greatest risk of becoming pregnant. (PsycINFO Database Record (c) 2011 APA, all rights reserved)