Vinyl azides in heterocyclic synthesis

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Adult Neurogenesis in Avian Auditory Cortex, Caudomedial Nidopallium (NCM): Lateralization and Effects of Statins

In the first part of this paper, we investigated the basic relationship between learning, memory and adult neurogenesis using zebra finches. We found that in the auditory cortex, the left hemisphere had more new neurons than the right hemisphere. This lateralization was correlated with song learning and memory. In the second part, we used juvenile zebra finches as a model organism to study the effects of Lipitor on learning, memory and neurogenesis. We found that Lipitor impaired song learning and memory storage. Lipitor treatments also changed the morphology of new neurons and size of old neurons, suggesting statins may affect neurons that are important to learning and memory during the critical learning period. In the last part, we investigated whether the degree of lipophilicity determines the effects of statins on memory and neurogenesis in adult birds. Our results showed that birds treated with hydrophilic pravastatin had weaker memory than control birds, suggesting that lipophilicity may not be the only factor that determines the effects of statins on memory

Using Ontology Fingerprints to evaluate genome-wide association study results

We describe an approach to characterize genes or phenotypes via ontology fingerprints which are composed of Gene Ontology (GO) terms overrepresented among those PubMed abstracts linked to the genes or phenotypes. We then quantify the biological relevance between genes and phenotypes by comparing their ontology fingerprints to calculate a similarity score. We validated this approach by correctly identifying genes belong to their biological pathways with high accuracy, and applied this approach to evaluate GWA study by ranking genes associated with the lipid concentrations in plasma as well as to prioritize genes within linkage disequilibrium (LD) block. We found that the genes with highest scores were: ABCA1, LPL, and CETP for HDL; LDLR, APOE and APOB for LDL; and LPL, APOA1 and APOB for triglyceride. In addition, we identified some top ranked genes linking to lipid metabolism from the literature even in cases where such knowledge was not reflected in current annotation of these genes. These results demonstrate that ontology fingerprints can be used effectively to prioritize genes from GWA studies for experimental validation

Current-Driven Magnetic Excitations in Permalloy-Based Multilayer Nanopillars

We study current-driven magnetization switching in nanofabricated Ni84Fe16/Cu/Ni84Fe16 trilayers at 295 K and 4.2 K. The shape of the hysteretic switching diagram at low magnetic field changes from 295 K to 4.2 K. The reversible behavior at higher field involves two phenomena, a threshold current for magnetic excitations closely correlated with the switching current, and a peak in differential resistance characterized by telegraph noise, with average period that decreases exponentially with current and shifts with temperature. We interpret both static and dynamic results at 295 K and 4.2 K in terms of thermal activation over a potential barrier, with a current dependent effective magnetic temperature.Comment: 4 pages, 4 Figure

Benefits of Using a Problem-Solving Scaffold for Teaching and Learning Synthesis in Undergraduate Organic Chemistry I

A problem-solving scaffold approach to synthesis was developed and implemented in two intervention sections of Chemistry 2211K (Organic Chemistry I) at Georgia Gwinnett College (GGC). A third section of Chemistry 2211K at GGC served as the control group for the experiment. Synthesis problems for chapter quizzes and the final examination were designed and administered to all sections participating in the experiment. Student solutions were graded according to a rubric designed to determine student use of the scaffold when solving synthesis problems. Analyses of the quiz results and the synthesis component of the final examination were conducted and intervention section students who employed the Synthesis Scaffold Approach were found to have higher mean scores on related graded events as compared to students who were not exposed to the Synthesis Scaffold Approach

Interventions for smoking cessation and reduction in individuals with schizophrenia

Background Patients with schizophrenia smoke more heavily than the general population and this contributes to their higher morbidity and mortality from smoking‐related illnesses. It remains unclear what interventions can help them to quit or reduce smoking. Objectives To evaluate the benefits and harms of different treatments for nicotine dependence in schizophrenia. Search methods We searched the Cochrane Tobacco Addiction Group Specialized Register and electronic databases including MEDLINE, EMBASE and PsycINFO from inception to April 2010. Selection criteria We included randomized trials for smoking cessation or reduction, comparing any pharmacological or non‐pharmacological intervention with placebo or with another therapeutic control in adult smokers with schizophrenia or schizoaffective disorder. Data collection and analysis Two reviewers independently assessed the eligibility and quality of trials and extracted data. Outcome measures included smoking abstinence, reduction in the amount smoked and any change in mental state. We extracted abstinence and reduction data at the end of treatment and at least six months after the intervention. We used the most rigorous definition of abstinence or reduction and biochemically validated data where available. Any reported adverse events were noted. Where appropriate, we pooled data using a random effects model. Main results We included 21 trials (11 trials of smoking cessation; four trials of smoking reduction; one trial for relapse prevention; five trials reported smoking outcomes for interventions aimed at other purposes). Seven trials compared bupropion with placebo; meta‐analysis showed that smoking cessation rates after bupropion were significantly higher than placebo at the end of treatment (seven trials, N=340; risk ratio [RR] 2.84; 95% confidence interval [CI] 1.61 to 4.99) and after six months (five trials, N=214, RR 2.78; 95% CI 1.02 to 7.58). Expired carbon monoxide (CO) level and the number of cigarettes smoked daily were significantly lower with bupropion at the end of therapy but not after six months. There were no significant differences in positive, negative and depressive symptoms between bupropion and placebo group. There was no report of major adverse event such as seizures with bupropion. Contingent reinforcement (CR) with money may increase smoking abstinence rates and reduce the level of smoking in patients with schizophrenia. However, it is uncertain whether these benefits are maintained in the longer term. There was no evidence of benefit for the few trials of other pharmacological therapies (including nicotine replacement therapy (NRT)) and psychosocial interventions in helping smokers with schizophrenia to quit or reduce smoking. Authors' conclusions Bupropion increases smoking abstinence rates in smokers with schizophrenia, without jeopardising their mental state. Bupropion may also reduce the amount these patients smoke. CR may help this group of patients to quit and reduce smoking. We failed to find convincing evidence that other interventions have a beneficial effect on smoking behaviour in schizophrenia

Detecting Spin-Polarized Currents in Ballistic Nanostructures

We demonstrate a mesoscopic spin polarizer/analyzer system that allows the spin polarization of current from a quantum point contact in an in-plane magnetic field to be measured. A transverse focusing geometry is used to couple current from an emitter point contact into a collector point contact. At large in-plane fields, with the point contacts biased to transmit only a single spin (g < e^2/h), the voltage across the collector depends on the spin polarization of the current incident on it. Spin polarizations of greater than 80% are found for both emitter and collector at 300mK and 7T in-plane field.Comment: related papers at http://marcuslab.harvard.ed

Circadian control of interferon-sensitive gene expression in murine skin.

The circadian clock coordinates a variety of immune responses with signals from the external environment to promote survival. We investigated the potential reciprocal relationship between the circadian clock and skin inflammation. We treated mice topically with the Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ) to activate IFN-sensitive gene (ISG) pathways and induce psoriasiform inflammation. IMQ transiently altered core clock gene expression, an effect mirrored in human patient psoriatic lesions. In mouse skin 1 d after IMQ treatment, ISGs, including the key ISG transcription factor IFN regulatory factor 7 (Irf7), were more highly induced after treatment during the day than the night. Nuclear localization of phosphorylated-IRF7 was most prominently time-of-day dependent in epidermal leukocytes, suggesting that these cell types play an important role in the diurnal ISG response to IMQ. Mice lacking Bmal1 systemically had exacerbated and arrhythmic ISG/Irf7 expression after IMQ. Furthermore, daytime-restricted feeding, which affects the phase of the skin circadian clock, reverses the diurnal rhythm of IMQ-induced ISG expression in the skin. These results suggest a role for the circadian clock, driven by BMAL1, as a negative regulator of the ISG response, and highlight the finding that feeding time can modulate the skin immune response. Since the IFN response is essential for the antiviral and antitumor effects of TLR activation, these findings are consistent with the time-of-day-dependent variability in the ability to fight microbial pathogens and tumor initiation and offer support for the use of chronotherapy for their treatment

Consistent Differential Expression Pattern (CDEP) on microarray to identify genes related to metastatic behavior

<p>Abstract</p> <p>Background</p> <p>To utilize the large volume of gene expression information generated from different microarray experiments, several meta-analysis techniques have been developed. Despite these efforts, there remain significant challenges to effectively increasing the statistical power and decreasing the Type I error rate while pooling the heterogeneous datasets from public resources. The objective of this study is to develop a novel meta-analysis approach, Consistent Differential Expression Pattern (CDEP), to identify genes with common differential expression patterns across different datasets.</p> <p>Results</p> <p>We combined False Discovery Rate (FDR) estimation and the non-parametric RankProd approach to estimate the Type I error rate in each microarray dataset of the meta-analysis. These Type I error rates from all datasets were then used to identify genes with common differential expression patterns. Our simulation study showed that CDEP achieved higher statistical power and maintained low Type I error rate when compared with two recently proposed meta-analysis approaches. We applied CDEP to analyze microarray data from different laboratories that compared transcription profiles between metastatic and primary cancer of different types. Many genes identified as differentially expressed consistently across different cancer types are in pathways related to metastatic behavior, such as ECM-receptor interaction, focal adhesion, and blood vessel development. We also identified novel genes such as <it>AMIGO2</it>, <it>Gem</it>, and <it>CXCL11 </it>that have not been shown to associate with, but may play roles in, metastasis.</p> <p>Conclusions</p> <p>CDEP is a flexible approach that borrows information from each dataset in a meta-analysis in order to identify genes being differentially expressed consistently. We have shown that CDEP can gain higher statistical power than other existing approaches under a variety of settings considered in the simulation study, suggesting its robustness and insensitivity to data variation commonly associated with microarray experiments.</p> <p><b>Availability</b>: CDEP is implemented in R and freely available at: <url>http://genomebioinfo.musc.edu/CDEP/</url></p> <p><b>Contact</b>: [email protected]</p