The androgen receptor plays different roles in macrophage-induced proliferation in prostate stromal cells between transitional and peripheral zones of benign prostatic hypertrophy

Macrophages play a critical role in the process of excessive stromal proliferation of benign prostatic hyperplasia (BPH). In our previous study, we used a BPH mouse model to elucidate a potential mechanism whereby macrophage infiltration promotes stromal cell proliferation in the prostate via the androgen receptor (AR)/inflammatory cytokine CCL3-dependent pathway. In our present study, we used the co-culture system of human macrophages and various prostatic zone stromal cells to further demonstrate that infiltrating macrophages promote prostatic stromal cell proliferation through stromal AR-dependent pathways, and we show that the stroma of TZ and PZ respond to macrophages differently because of differences in stromal AR signaling; this could possibly be one of the key pathways for stromal expansion during BPH development and progression. We hypothesize that AR and different downstream inflammatory mediators between TZ and PZ could serve as potential targets for the future design of therapeutic agents for BPH and our results provide significant insights into the search for targeted therapeutic approaches to battle BPH

FERN: Leveraging Graph Attention Networks for Failure Evaluation and Robust Network Design

Robust network design, which aims to guarantee network availability under various failure scenarios while optimizing performance/cost objectives, has received significant attention. Existing approaches often rely on model-based mixed-integer optimization that is hard to scale or employ deep learning to solve specific engineering problems yet with limited generalizability. In this paper, we show that failure evaluation provides a common kernel to improve the tractability and scalability of existing solutions. By providing a neural network function approximation of this common kernel using graph attention networks, we develop a unified learning-based framework, FERN, for scalable Failure Evaluation and Robust Network design. FERN represents rich problem inputs as a graph and captures both local and global views by attentively performing feature extraction from the graph. It enables a broad range of robust network design problems, including robust network validation, network upgrade optimization, and fault-tolerant traffic engineering that are discussed in this paper, to be recasted with respect to the common kernel and thus computed efficiently using neural networks and over a small set of critical failure scenarios. Extensive experiments on real-world network topologies show that FERN can efficiently and accurately identify key failure scenarios for both OSPF and optimal routing scheme, and generalizes well to different topologies and input traffic patterns. It can speed up multiple robust network design problems by more than 80x, 200x, 10x, respectively with negligible performance gap

UV/Vis+ Photochemistry Database : Structure, Content and Applications

Acknowledgments This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. However, the authors are indebted to those colleagues who support us in maintaining the database through the provision of spectral and other photochemical data and information. The National Center for Atmospheric Research is operated by the University Coporation for Atmopsheric Research, under the sponsorship of the National Science Foundation. Disclaimer: The views expressed in this paper are those of the authors and do not necessarily represent the views or policies of the U.S.EPA. Mention of trade names or products does not convey and should not be interpreted as conveying official U.S. EPA approval, endorsement, or recommendation.Peer reviewedPublisher PD

Epidemic clones, oceanic gene pools and eco-LD in the free living marine pathogen Vibrio parahaemolyticus

We investigated global patterns of variation in 157 whole genome sequences of Vibrio parahaemolyticus, a free-living and seafood associated marine bacterium. Pandemic clones, responsible for recent outbreaks of gastroenteritis in humans have spread globally. However, there are oceanic gene pools, one located in the oceans surrounding Asia and another in the Mexican Gulf. Frequent recombination means that most isolates have acquired the genetic profile of their current location. We investigated the genetic structure in the Asian gene pool by calculating the effective population size in two different ways. Under standard neutral models, the two estimates should give similar answers but we found a thirty fold difference. We propose that this discrepancy is caused by the subdivision of the species into a hundred or more ecotypes which are maintained stably in the population. To investigate the genetic factors involved, we used 51 unrelated isolates to conduct a genome-wide scan for epistatically interacting loci. We found a single example of strong epistasis between distant genome regions. A majority of strains had a type VI secretion system associated with bacterial killing. The remaining strains had genes associated with biofilm formation and regulated by c-di-GMP signaling. All strains had one or other of the two systems and none of isolate had complete complements of both systems, although several strains had remnants. Further top-down analysis of patterns of linkage disequilibrium within frequently recombining species will allow a detailed understanding of how selection acts to structure the pattern of variation within natural bacterial populations

Spatio-temporal analysis of malaria incidence at the village level in a malaria-endemic area in Hainan, China

<p>Abstract</p> <p>Background</p> <p>Malaria incidence in China's Hainan province has dropped significantly, since Malaria Programme of China Global Fund Round 1 was launched. To lay a foundation for further studies to evaluate the efficacy of Malaria Programme and to help with public health planning and resource allocation in the future, the temporal and spatial variations of malaria epidemic are analysed and areas and seasons with a higher risk are identified at a fine geographic scale within a malaria endemic county in Hainan.</p> <p>Methods</p> <p>Malaria cases among the residents in each of 37 villages within hyper-endemic areas of Wanning county in southeast Hainan from 2005 to 2009 were geo-coded at village level based on residence once the patients were diagnosed. Based on data so obtained, purely temporal, purely spatial and space-time scan statistics and geographic information systems (GIS) were employed to identify clusters of time, space and space-time with elevated proportions of malaria cases.</p> <p>Results</p> <p>Purely temporal scan statistics suggested clusters in 2005,2006 and 2007 and no cluster in 2008 and 2009. Purely spatial clustering analyses pinpointed the most likely cluster as including three villages in 2005 and 2006 respectively, sixteen villages in 2007, nine villages in 2008, and five villages in 2009, and the south area of Nanqiao town as the most likely to have a significantly high occurrence of malaria. The space-time clustering analysis found the most likely cluster as including three villages in the south of Nanqiao town with a time frame from January 2005 to May 2007.</p> <p>Conclusions</p> <p>Even in a small traditional malaria endemic area, malaria incidence has a significant spatial and temporal heterogeneity on the finer spatial and temporal scales. The scan statistics enable the description of this spatiotemporal heterogeneity, helping with clarifying the epidemiology of malaria and prioritizing the resource assignment and investigation of malaria on a finer geographical scale in endemic areas.</p

Hepatoma Cell-Derived Extracellular Vesicles Promote Liver Cancer Metastasis by Inducing the Differentiation of Bone Marrow Stem Cells Through microRNA-181d-5p and the FAK/Src Pathway

Bone marrow mesenchymal stem cells (BMSCs) are beneficial to repair the damaged liver. Tumor-derived extracellular vesicles (EV) are notorious in tumor metastasis. But the mechanism underlying hepatoma cell-derived EVs in BMSCs and liver cancer remains unclear. We hypothesize that hepatoma cell-derived EVs compromise the effects of BMSCs on the metastasis of liver cancer. The differentially expressed microRNAs (miRNAs) were screened. HepG2 cells were transfected with miR-181d-5p mimic or inhibitor, and the EVs were isolated and incubated with BMSCs to evaluate the differentiation of BMSCs into fibroblasts. Hepatoma cells were cultured with BMSCs conditioned medium (CM) treated with HepG2-EVs to assess the malignant behaviors of hepatoma cells. The downstream genes and pathways of miR-181d-5p were analyzed and their involvement in the effect of EVs on BMSC differentiation was verified through functional rescue experiments. The nude mice were transplanted with BMSCs-CM or BMSCs-CM treated with HepG2-EVs, and then tumor growth and metastasis in vivo were assessed. HepG2-EVs promoted fibroblastic differentiation of BMSCs, and elevated levels of α-SMA, vimentin, and collagen in BMSCs. BMSCs-CM treated with HepG2-EVs stimulated the proliferation, migration, invasion and epithelial-mesenchymal-transition (EMT) of hepatoma cells. miR-181d-5p was the most upregulated in HepG2-EVs-treated BMSCs. miR-181d-5p targeted SOCS3 to activate the FAK/Src pathway and SOCS3 overexpression inactivated the FAK/Src pathway. Reduction of miR-181d-5p in HepG2-EVs or SOCS3 overexpression reduced the differentiation of BMSCs into fibroblasts, and compromised the promoting effect of HepG2-EVs-treated BMSCs-CM on hepatoma cells. In vivo, HepG2-EVs-treated BMSCs facilitated liver cancer growth and metastasis. In conclusion, HepG2-EVs promote the differentiation of BMSCs, and promote liver cancer metastasis through the delivery of miR-181d-5p and the SOCS3/FAK/Src pathway

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Synthesis and characterization of ZrO2 hollow spheres

ZrO2 hollow microspheres with the average diameter of about 500 nm and the shell thickness of about 50 nm were synthesized by a facile technique using carbon spheres as templates. The corresponding ZrO2 hollow microspheres were obtained by calcining the precursors of C-Zr(OH)(4) core-shell heterostructures, which were synthesized with the precipitation of ZrCl4 solution with aqueous ammonia on the surface of colloid carbons. SEM, XRD, TGA and BET were used to characterize the composition, morphology, size and crystal structure of synthesized products. The effects of ultrasonic dispersion and separation process on the hollow spheres were studied, and the surfactant PEG-1000 was added to tune the shell structure of synthesized ZrO2 hollow spheres. (C) 2009 Elsevier B.V. All rights reserved

Fabrication of Monodisperse Magnetite Hollow Spheres

Monodisperse Fe(3)O(4) hollow spheres with average diameter of 400 nm and shell thickness of 60 nm were prepared through a one-pot solvothermal process with the presence of NH(4)Ac as the structure-directing agent, and a novel gas-bubble-assisted Ostwald ripening process was proposed to explain the formation of hollow structures. According to this mechanism, hollow Fe(3)O(4) and MnFe(2)O(4) ferrite microspheres with controlled particle size were obtained using urea and ammonia as the structure-directing agents, and porous Fe(3)O(4) spheres with particle size of 100 nm and pore size of 10 nm were obtained by the assistance of bicarbonate of ammonia. X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and high-resolution transmission electron microscopy were used to characterize the structure of synthesized products, and the magnetic property investigation shows that the hollow microspheres exhibit a ferromagnetic behavior and possess a higher saturation magnetization (M(s)) than that of the solid microspheres

Mismatch Negativity to Threatening Voices associated with Positive Symptoms in Schizophrenia

Although the general consensus holds that emotional perception is impaired in patients with schizophrenia, the extent to which neural processing of emotional voices is altered in schizophrenia remains to be determined. This study enrolled 30 patients with chronic schizophrenia and 30 controls and measured their mismatch negativity (MMN), a component of auditory event-related potentials (ERP). In a passive oddball paradigm, happily or angrily spoken deviant syllables dada were randomly presented within a train of emotionally neutral standard syllables. Results showed that MMN in response to angry syllables and angry-derived nonvocal sounds was significantly decreased in individuals with schizophrenia. P3a to angry syllables showed stronger amplitudes but longer latencies. Weaker MMN amplitudes were associated with more positive symptoms of schizophrenia. Receiver operator characteristic analysis revealed that angry MMN, angry-derived MMN, and angry P3a could help predict whether someone had received a clinical diagnosis of schizophrenia. The findings suggested general impairments of voice perception and acoustic discrimination in patients with chronic schizophrenia. The emotional salience processing of voices showed an atypical fashion at the preattentive level, being associated with positive symptoms in schizophrenia