Learning a Hybrid Architecture for Sequence Regression and Annotation

When learning a hidden Markov model (HMM), sequen- tial observations can often be complemented by real-valued summary response variables generated from the path of hid- den states. Such settings arise in numerous domains, includ- ing many applications in biology, like motif discovery and genome annotation. In this paper, we present a flexible frame- work for jointly modeling both latent sequence features and the functional mapping that relates the summary response variables to the hidden state sequence. The algorithm is com- patible with a rich set of mapping functions. Results show that the availability of additional continuous response vari- ables can simultaneously improve the annotation of the se- quential observations and yield good prediction performance in both synthetic data and real-world datasets.Comment: AAAI 201

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A Bayesian Model for Nucleosome Positioning Using DNase-seq Data

<p>As fundamental structural units of the chromatin, nucleosomes are involved in virtually all aspects of genome function. Different methods have been developed to map genome-wide nucleosome positions, including MNase-seq and a recent chemical method requiring genetically engineered cells. However, these methods are either low resolution and prone to enzymatic sequence bias or require genetically modified cells. The DNase I enzyme has been used to probe nucleosome structure since the 1960s, but in the current high throughput sequencing era, DNase-seq has mainly been used to study regulatory sequences known as DNase hypersensitive sites. This thesis shows that DNase-seq data is also very informative about nucleosome positioning. The distinctive oscillatory DNase I cutting patterns on nucleosomal DNA are shown and discussed. Based on these patterns, a Bayes factor is proposed to be used for distinguishing nucleosomal and non-nucleosomal genome positions. The results show that this approach is highly sensitive and specific. A Bayesian method that simulates the data generation process and can provide more interpretable results is further developed based on the Bayes factor investigations. Preliminary results on a test genomic region show that the Bayesian model works well in identifying nucleosome positioning. Estimated posterior distributions also agree with some known biological observations from external data. Taken together, methods developed in this thesis show that DNase-seq can be used to identify nucleosome positioning, adding great value to this widely utilized protocol.</p>Thesi

Renal denervation inhibits the renin–angiotensin–aldosterone system in spontaneously hypertensive rats

This study was conducted to explore the effect of renal denervation (RDN) on the renin–angiotensin–aldosterone system (RAAS) in spontaneously hypertensive rats (SHRs). Our experimental rats were randomly divided into the RDN group conducted by painting 10% phenol on the bilateral renal nerves (RDNX), the shamoperation group simply painting with saline (Sham), and the normotension control group (WKY) following all the animal blood and tissues of kidney, hypothalamus, and adrenal gland collected and examined 2 weeks after RDN operation. We found that the aldosterone (ALD) levels in serum and tissues all decreased in the RDNX group compared with the Sham group (p < .05). Meantime, the expression of angiotensin II type1 receptor (AT1R) mRNA also exhibited significantly reduced by 2.22-fold in the RDNX group compared to the Sham group identical to the expression of AT1R protein in the renal cortex and outer stripe of the outer medulla (OSOM) subjected to denervation surgery, which manifested the lower ATIR protein expression than the Sham group (p < .05). Besides, the expression of angiotensin II (Ang II) protein in the cortex , OSOM, and inner stripe of the outer medulla were all attenuated by RDN in comparison with the Sham group (p < .05). RDN reduced intrarenal RAAS and circulating RAAS to lower blood pressure and repair renal function

Selenoprotein S Attenuates Tumor Necrosis Factor-α-Induced Dysfunction in Endothelial Cells

Endothelial dysfunction, partly induced by inflammatory mediators, is known to initiate and promote several cardiovascular diseases. Selenoprotein S (SelS) has been identified in endothelial cells and is associated with inflammation; however, its function in inflammation-induced endothelial dysfunction has not been described. We first demonstrated that the upregulation of SelS enhances the levels of nitric oxide and endothelial nitric oxide synthase in tumor necrosis factor- (TNF-) α-treated human umbilical vein endothelial cells (HUVECs). The levels of TNF-α-induced endothelin-1 and reactive oxygen species are also reduced by the upregulation of SelS. Furthermore, SelS overexpression blocks the TNF-α-induced adhesion of THP-1 cells to HUVECs and inhibits the increase in intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Moreover, SelS overexpression regulates TNF-α-induced inflammatory factors including interleukin-1β, interleukin-6, interleukin-8, and monocyte chemotactic protein-1 and attenuates the TNF-α-induced activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways. Conversely, the knockdown of SelS with siRNA results in an enhancement of TNF-α-induced injury in HUVECs. These findings suggest that SelS protects endothelial cells against TNF-α-induced dysfunction by inhibiting the activation of p38 MAPK and NF-κB pathways and implicates it as a possible modulator of vascular inflammatory diseases

Particuology

Graphene/hierarchy structure manganese dioxide (GN/MnO2) composites were synthesized using a simple microwave-hydrothermal method. The properties of the prepared composites were analyzed using field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) measurements. The electrochemical performances of the composites were analyzed using cyclic voltammetry, electrochemical impedance spectrometry (EIS), and chronopotentiometry. The results showed that GN/MnO2 (10 wt% graphene) displayed a specific capacitance of 244 F/g at a current density of 100 mA/g. An excellent cyclic stability was obtained with a capacity retention of approximately 94.3% after 500 cycles in a 1 mol/L Li2SO4 solution. The improved electrochemical performance is attributed to the hierarchy structure of the manganese dioxide, which can enlarge the interface between the active materials and the electrolyte. The preparation route provides a new approach for hierarchy structure graphene composites; this work could be readily extended to the preparation of other graphene-based composites with different structures for use in energy storage devices. (C) 2013 Chinese Society of Particuology and Institute of Process Engineering, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.Graphene/hierarchy structure manganese dioxide (GN/MnO2) composites were synthesized using a simple microwave-hydrothermal method. The properties of the prepared composites were analyzed using field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) measurements. The electrochemical performances of the composites were analyzed using cyclic voltammetry, electrochemical impedance spectrometry (EIS), and chronopotentiometry. The results showed that GN/MnO2 (10 wt% graphene) displayed a specific capacitance of 244 F/g at a current density of 100 mA/g. An excellent cyclic stability was obtained with a capacity retention of approximately 94.3% after 500 cycles in a 1 mol/L Li2SO4 solution. The improved electrochemical performance is attributed to the hierarchy structure of the manganese dioxide, which can enlarge the interface between the active materials and the electrolyte. The preparation route provides a new approach for hierarchy structure graphene composites; this work could be readily extended to the preparation of other graphene-based composites with different structures for use in energy storage devices. (C) 2013 Chinese Society of Particuology and Institute of Process Engineering, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved

Microwave-hydrothermal preparation of a graphene/hierarchy structure MnO_2 composite for a supercapacitor

Schematic illustration of fabrication process for GN 2 composite. Display omitte

Emotional Body-Word Conflict Evokes Enhanced N450 and Slow Potential

<div><p>Emotional conflict refers to the influence of task irrelevant affective stimuli on current task set. Previously used emotional face-word tasks have produced certain electrophysiological phenomena, such as an enhanced N450 and slow potential; however, it remains unknown whether these effects emerge in other tasks. The present study used an emotional body-word conflict task to investigate the neural dynamics of emotional conflict as reflected by response time, accuracy, and event-related potentials, which were recorded with the aim of replicating the previously observed N450 and slow potential effect. Results indicated increased response time and decreased accuracy in the incongruent condition relative to the congruent condition, indicating a robust interference effect. Furthermore, the incongruent condition evoked pronounced N450 amplitudes and a more positive slow potential, which might be associated with conflict-monitoring and conflict resolution. The present findings extend our understanding of emotional conflict to the body-word domain.</p> </div