A superconducting magnetic spectrometer for cosmic ray nuclei

Equipment specifications for balloon carried superconducting magnetic spectrometer to measure spectra of cosmic ray nuclei with charges ranging from protons to iro

Computer simulation of protein systems

Ligand binding to dihydrofolate reductase (DHFR) is discussed. This is an extremely important enzyme, as it is the target of several drugs (inhibitors) which are used clinically as antibacterials, antiprotozoals and in cancer chemotherapy. DHFR catalyzes the NADPH (reduced nicotinamide adenine dinucleotide phosphate) dependent reduction of dihydrofolate to tetrahydrofolate, which is used in several pathways of purine and pyrimidine iosynthesis, including that of thymidylate. Since DNA synthesis is dependent on a continuing supply of thymidylate, a blockade of DHFR resulting in a depletion of thymidylate can lead to the cessation of growth of a rapidly proliferating cell line. DHFR exhibits a significant species to species variability in its sensitivity to various inhibitors. For example, trimethoprim, an inhibitor of DHFR, binds to bacterial DHFR's 5 orders of magnitude greater than to vertebrate DHFR's. The structural mechanics, dynamics and energetics of a family of dihydrofolate reductases are studied to rationalize the basis for the inhibitor of these enyzmes and to understand the molecular basis of the difference in the binding constants between the species. This involves investigating the conformational changes induced in the protein on binding the ligand, the internal strain imposed by the enzyme on the ligand, the restriction of fluctuations in atom positions due to binding and the consequent change in entropy

Ebola virus VP35 induces high-level production of recombinant TPL-2–ABIN-2–NF-κB1 p105 complex in co-transfected HEK-293 cells

Activation of PKR (double-stranded-RNA-dependent protein kinase) by DNA plasmids decreases translation, and limits the amount of recombinant protein produced by transiently transfected HEK (human embryonic kidney)-293 cells. Co-expression with Ebola virus VP35 (virus protein 35), which blocked plasmid activation of PKR, substantially increased production of recombinant TPL-2 (tumour progression locus 2)–ABIN-2 [A20-binding inhibitor of NF-κB (nuclear factor κB) 2]–NF-κB1 p105 complex. VP35 also increased expression of other co-transfected proteins, suggesting that VP35 could be employed generally to boost recombinant protein production by HEK-293 cells

K^+ momentum spectrum from (K^-,K^+) reactions in intranuclear cascade model

In a framework of intranuclear cascade (INC) type calculation, we study a momentum spectrum in reactions \KK at a beam momentum of 1.65 GeV/c. INC model calculations are compared with the relativistic impulse approximation (RIA) calculations to perform the detailed study of the reaction mechanism. We find that the INC model can reproduce the experimental data on various targets. Especially, in the low-momentum region, the forward-angle cross sections of the $(K^-,K^+)$ reaction on from light to heavy targets are consistently explained with the two-step strangeness exchange and production processes with various intermediate mesons, and $\phi$, $a_0$ and $f_0$ productions and their decay into $K^+K^-$. In the two-step processes, inclusion of meson and hyperon resonances is found to be essential.Comment: LaTeX file and 12ps figure

Nocturnal Dexamethasone versus Hydrocortisone for the Treatment of Children with Congenital Adrenal Hyperplasia

Classic congenital adrenal hyperplasia affects approximately 1 in 15,000 children. Current treatment strategies using multiple daily doses of hydrocortisone lead to suboptimal outcomes. We tested the hypothesis that nocturnal administration of dexamethasone will suppress the hypothalamic-pituitary-adrenal axis more effectively than standard hydrocortisone treatment by blocking the inherent diurnal secretion of ACTH. We performed a pilot study of five prepubertal patients comparing CAH control during two 24-hour hospitalizations, one on hydrocortisone and the other on dexamethasone. The patterns of adrenal suppression differed markedly between hydrocortisone and nocturnal dexamethasone, with significant suppression of the morning rise in ACTH, 17-hydroxyprogesterone, and androstenedione while on dexamethasone. On hydrocortisone therapy, there is a marked variation in ACTH and adrenal hormones depending on time of day and timing of hydrocortisone administration. Longer-term studies are needed to investigate the lowest effective dose and potential toxicity of nocturnal dexamethasone to determine its utility as a therapy for CAH

Mathematically Gifted Adolescents Have Deficiencies in Social Valuation and Mentalization

Many mathematically gifted adolescents are characterized as being indolent, underachieving and unsuccessful despite their high cognitive ability. This is often due to difficulties with social and emotional development. However, research on social and emotional interactions in gifted adolescents has been limited. The purpose of this study was to observe differences in complex social strategic behaviors between gifted and average adolescents of the same age using the repeated Ultimatum Game. Twenty-two gifted adolescents and 24 average adolescents participated in the Ultimatum Game. Two adolescents participate in the game, one as a proposer and the other as a responder. Because of its simplicity, the Ultimatum Game is an apt tool for investigating complex human emotional and cognitive decision-making in an empirical setting. We observed strategic but socially impaired offers from gifted proposers and lower acceptance rates from gifted responders, resulting in lower total earnings in the Ultimatum Game. Thus, our results indicate that mathematically gifted adolescents have deficiencies in social valuation and mentalization

Linking Session Focus to Treatment Outcome in Evidence-Based Treatments for Adolescent Substance Abuse

The relation between specific therapy techniques and treatment outcome was examined for 2 empirically supported treatments for adolescent substance abuse: individual cognitive–behavioral therapy and multidimensional family therapy. Participants were 51 inner-city, substance-abusing adolescents receiving outpatient psychotherapy within a larger randomized trial. One session per case was evaluated using a 17-item observational measure of model-specific techniques and therapeutic foci. Exploratory factor analysis identified 2 subscales, Adolescent Focus and Family Focus, with strong interrater reliability and internal consistency. Process–outcome analyses revealed that family focus, but not adolescent focus, predicted posttreatment improvement in drug use, externalizing symptoms, and internalizing symptoms within both study conditions. Implications for the implementation and dissemination of individual-based and family-based approaches for adolescent drug use are discussed