Use of Microtremors for the Estimation of Ground Vibration Characteristics

Short-period micro tremor array observation is conducted at five sites in the Tokyo Metropolitan area of Japan. The Fourier spectra of horizontal and vertical components show variations in time, but their ratio is stable for different time instants. The characteristics of the amplitude ratio are similar to that of Rayleigh wave and the period correspond to the peak ratio correspond to the predominant period of the sites for shear wave propagation. A parametric study for two-layered models reveals that the peaks for Rayleigh wave and shear wave are close for the ground having large impedance ratio. The F-K spectrum analysis using vertical components obtained the phase velocity close to the dispersion curve for the Rayleigh wave

Experimental Demonstration of Macroscopic Quantum Coherence in Gaussian States

We witness experimentally the presence of macroscopic coherence in Gaussian quantum states using a recently proposed criterion (E.G. Cavalcanti and M. Reid, Phys. Rev. Lett. 97, 170405 (2006)). The macroscopic coherence stems from interference between macroscopically distinct states in phase space and we prove experimentally that even the vacuum state contains these features with a distance in phase space of $0.51\pm0.02$ shot noise units (SNU). For squeezed states we found macroscopic superpositions with a distance of up to $0.83\pm0.02$ SNU. The proof of macroscopic quantum coherence was investigated with respect to squeezing and purity of the states.Comment: 5 pages, 6 figure

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

Spatial epidemiology of American cutaneous leishmaniasis in a municipality of west São Paulo State, Brazil

Background & objectives: In the last decade, in the state of São Paulo, 5898 cases of cutaneous leishmaniasis (CL) were reported. This study was undertaken to analyze the epidemiology of CL in the municipality of Teodoro Sampaio, in São Paulo State, Brazil, based on a geographic approach, as very little is known of the relationship between CL and the spatial transformation process. Methods: This is a population-based quantitative, descriptive and cross-sectional case study. Surveys of the official notifications in the healthcare center and official sources from 1998 to 2011 were analysed. The data were described based on statistics and the Kernel method to detect hotspots of transmission. Results: The age group between 21 and 40 yr was most affected, with 24 cases (57.9%). Of the 41 cases reported between 1998 and 2011, 33 cases were having low education status and 31 cases (75.6%) were males. The spatial and temporal distribution was aggregated in three-year periods which permitted the identification of two microfoci, in periods I (1998–2000) and III (2005–2007). Interpretation & conclusion: The disease has presented, in recent years, a pattern of sporadic transmission or microfoci, and continues to maintain enzootic cycles of Leishmania in a sylvatic environment, ensuring the perpetuation of the pathogen in nature, and the risk of emergence of new cases of CL in domestic animals and humans

Chemical structure-guided design of dynapyrazoles, potent cell-permeable dynein inhibitors with a unique mode of action

Cytoplasmic dyneins are motor proteins in the AAA+ superfamily that transport cellular cargos toward microtubule minus-ends. Recently, ciliobrevins were reported as selective cell-permeable inhibitors of cytoplasmic dyneins. As is often true for first-in-class inhibitors, the use of ciliobrevins has in part been limited by low potency. Moreover, suboptimal chemical properties, such as the potential to isomerize, have hindered efforts to improve ciliobrevins. Here, we characterized the structure of ciliobrevins and designed conformationally constrained isosteres. These studies identified dynapyrazoles, inhibitors more potent than ciliobrevins. At single-digit micromolar concentrations dynapyrazoles block intraflagellar transport in the cilium and lysosome motility in the cytoplasm, processes that depend on cytoplasmic dyneins. Further, we find that while ciliobrevins inhibit both dynein's microtubule-stimulated and basal ATPase activity, dynapyrazoles strongly block only microtubule-stimulated activity. Together, our studies suggest that chemical-structure-based analyses can lead to inhibitors with improved properties and distinct modes of inhibition

Insulin Concentration Modulates Hepatic Lipid Accumulation in Mice in Part via Transcriptional Regulation of Fatty Acid Transport Proteins

Fatty liver disease (FLD) is commonly associated with insulin resistance and obesity, but interestingly it is also observed at low insulin states, such as prolonged fasting. Thus, we asked whether insulin is an independent modulator of hepatic lipid accumulation.In mice we induced, hypo- and hyperinsulinemia associated FLD by diet induced obesity and streptozotocin treatment, respectively. The mechanism of free fatty acid induced steatosis was studied in cell culture with mouse liver cells under different insulin concentrations, pharmacological phosphoinositol-3-kinase (PI3K) inhibition and siRNA targeted gene knock-down. We found with in vivo and in vitro models that lipid storage is increased, as expected, in both hypo- and hyperinsulinemic states, and that it is mediated by signaling through either insulin receptor substrate (IRS) 1 or 2. As previously reported, IRS-1 was up-regulated at high insulin concentrations, while IRS-2 was increased at low levels of insulin concentration. Relative increase in either of these insulin substrates, was associated with an increase in liver-specific fatty acid transport proteins (FATP) 2&5, and increased lipid storage. Furthermore, utilizing pharmacological PI3K inhibition we found that the IRS-PI3K pathway was necessary for lipogenesis, while FATP responses were mediated via IRS signaling. Data from additional siRNA experiments showed that knock-down of IRSs impacted FATP levels.States of perturbed insulin signaling (low-insulin or high-insulin) both lead to increased hepatic lipid storage via FATP and IRS signaling. These novel findings offer a common mechanism of FLD pathogenesis in states of both inadequate (prolonged fasting) and ineffective (obesity) insulin signaling