In situ–Directed Growth of Organic Nanofibers and Nanoflakes: Electrical and Morphological Properties

Organic nanostructures made from organic molecules such as para-hexaphenylene (p-6P) could form nanoscale components in future electronic and optoelectronic devices. However, the integration of such fragile nanostructures with the necessary interface circuitry such as metal electrodes for electrical connection continues to be a significant hindrance toward their large-scale implementation. Here, we demonstrate in situ–directed growth of such organic nanostructures between pre-fabricated contacts, which are source–drain gold electrodes on a transistor platform (bottom-gate) on silicon dioxide patterned by a combination of optical lithography and electron beam lithography. The dimensions of the gold electrodes strongly influence the morphology of the resulting structures leading to notably different electrical properties. The ability to control such nanofiber or nanoflake growth opens the possibility for large-scale optoelectronic device fabrication

Non-identical smoothing operators for estimating time-frequency interdependence in electrophysiological recordings

Synchronization of neural activity from distant parts of the brain is crucial for the coordination of cognitive activities. Because neural synchronization varies both in time and frequency, time–frequency (T-F) coherence is commonly employed to assess interdependences in electrophysiological recordings. T-F coherence entails smoothing the cross and power spectra to ensure statistical consistency of the estimate, which reduces its T-F resolution. This trade-off has been described in detail when the cross and power spectra are smoothed using identical smoothing operators, which may yield spurious coherent frequencies. In this article, we examine the use of non-identical smoothing operators for the estimation of T-F interdependence, i.e., phase synchronization is characterized by phase locking between signals captured by the cross spectrum and we may hence improve the trade-off by selectively smoothing the auto spectra. We first show that the frequency marginal density of the present estimate is bound within [0,1] when using non-identical smoothing operators. An analytic calculation of the bias and variance of present estimators is performed and compared with the bias and variance of standard T-F coherence using Monte Carlo simulations. We then test the use of non-identical smoothing operators on simulated data, whose T-F properties are known through construction. Finally, we analyze empirical data from eyes-closed surface electroencephalography recorded in human subjects to investigate alpha-band synchronization. These analyses show that selectively smoothing the auto spectra reduces the bias of the estimator and may improve the detection of T-F interdependence in electrophysiological data at high temporal resolution

Advertising Bans and the Substitutability of Online and Offline Advertising

The authors examine whether the growth of the Internet has reduced the effectiveness of government regulation of advertising. They combine nonexperimental variation in local regulation of offline alcohol advertising with data from field tests that randomized exposure to online advertising for 275 different online advertising campaigns to 61,580 people. The results show that people are 8% less likely to say that they will purchase an alcoholic beverage in states that have alcohol advertising bans compared with states that do not. For consumers exposed to online advertising, this gap narrows to 3%. There are similar effects for four changes in local offline alcohol advertising restrictions when advertising effectiveness is observed both before and after the change. The effect of online advertising is disproportionately high for new products and for products with low awareness in places that have bans. This suggests that online advertising could reduce the effectiveness of attempts to regulate offline advertising channels because online advertising substitutes for (rather than complements) offline advertising.Google (Firm)WPP (Firm

Checkpoint kinase inhibitor AZD7762 strongly sensitises urothelial carcinoma cells to gemcitabine

Background: More effective chemotherapies are urgently needed for bladder cancer, a major cause of morbidity and mortality worldwide. We therefore explored the efficacy of the combination of gemcitabine and AZD7762, a checkpoint kinase 1/2 (CHK1/2) inhibitor, for bladder cancer. Methods: Viability, clonogenicity, cell cycle distribution and apoptosis were assessed in urothelial cancer cell lines and various non-malignant urothelial cells treated with gemcitabine and AZD7762. DNA damage was assessed by ?H2A.X and 53-BP1 staining and checkpoint activation was followed by Western blotting. Pharmacological inhibition of CHK1 and CHK2 was compared to downregulation of either CHK1 or CHK2 using siRNAs. Results: Combined use of gemcitabine and AZD7762 synergistically reduced urothelial carcinoma cell viability and colony formation relative to either single treatment. Non-malignant urothelial cells were substantially less sensitive to this drug combination. Gemcitabine plus AZD7762 inhibited cell cycle progression causing cell accumulation in S-phase. Moreover, the combination induced pronounced levels of apoptosis as indicated by an increase in the fraction of sub-G1 cells, in the levels of cleaved PARP, and in caspase 3/7 activity. Mechanistic investigations showed that AZD7762 treatment inhibited the repair of gemcitabine-induced double strand breaks by interference with CHK1, since siRNA-mediated depletion of CHK1 but not of CHK2 mimicked the effects of AZD7762. Conclusions: AZD7762 enhanced sensitivity of urothelial carcinoma cells to gemcitabine by inhibiting DNA repair and disturbing checkpoints. Combining gemcitabine with CHK1 inhibition holds promise for urothelial cancer therapy

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Microarray analysis reveals similarity between CD8+CD28– T cells from young and elderly persons, but not of CD8+CD28+ T cells

We isolated highly purified CD8+CD28+ and CD8+CD28– T cells populations from healthy young and elderly persons for gene expression profiling using Affymetrix oligonucleotide microarrays. We demonstrate that the gene expression profile of CD8+CD28– T cells is very similar in young and elderly persons. In contrast, CD8+CD28+ in elderly differ from CD8+CD28+ in young persons. Hierarchical clustering revealed that CD8+CD28+ in elderly are located between CD8+CD28+ in young and CD8+CD28– (young and old) T cells regarding their differentiation state. Our study demonstrates a dichotomy of gene expression levels between CD8+CD28+ T cells in young and elderly persons but a similarity between CD8+CD28– T cells in young and elderly persons. As CD8+CD28+ T cells from elderly and young persons are distinct due to a different composition of the population, these results suggest that the gene expression profile does not depend on chronological age but depends on the differentiation state of the individual cell types. The original publication is available at www.springerlink.co