Miracle-dz/UniFAR-FTUs huggingface dataset:
Nucleosome Repositioning: A Novel Mechanism for Nicotine- and Cocaine-Induced Epigenetic Changes

Drugs of abuse modify behavior by altering gene expression in the brain. Gene expression can be regulated by changes in DNA methylation as well as by histone modifications, which alter chromatin structure, DNA compaction and DNA accessibility. In order to better understand the molecular mechanisms directing drug-induced changes in chromatin structure, we examined DNA-nucleosome interactions within promoter regions of 858 genes in human neuroblastoma cells (SH-SY5Y) exposed to nicotine or cocaine. Widespread, drug- and time-resolved repositioning of nucleosomes was identified at the transcription start site and promoter region of multiple genes. Nicotine and cocaine produced unique and shared changes in terms of the numbers and types of genes affected, as well as repositioning of nucleosomes at sites which could increase or decrease the probability of gene expression based on DNA accessibility. Half of the drug-induced nucleosome positions approximated a theoretical model of nucleosome occupancy based on physical and chemical characteristics of the DNA sequence, whereas the basal or drug naïve positions were generally DNA sequence independent. Thus we suggest that nucleosome repositioning represents an initial dynamic genome-wide alteration of the transcriptional landscape preceding more selective downstream transcriptional reprogramming, which ultimately characterizes the cell- and tissue-specific responses to drugs of abuse.
Tumor Site Immune Markers Associated with Risk for Subsequent Basal Cell Carcinomas

Background Basal cell carcinoma (BCC) tumors are the most common skin cancer and are highly immunogenic. Objective The goal of this study was to assess how immune-cell related gene expression in an initial BCC tumor biopsy was related to the appearance of subsequent BCC tumors. Materials and Methods Levels of mRNA for CD3ε (a T-cell receptor marker), CD25 (the alpha chain of the interleukin (IL)-2 receptor expressed on activated T-cells and B-cells), CD68 (a marker for monocytes/macrophages), the cell surface glycoprotein intercellular adhesion molecule-1 (ICAM-1), the cytokine interferon-γ (IFN-γ) and the anti-inflammatory cytokine IL-10 were measured in BCC tumor biopsies from 138 patients using real-time PCR. Results The median follow-up was 26.6 months, and 61% of subjects were free of new BCCs two years post-initial biopsy. Patients with low CD3ε CD25, CD68, and ICAM-1 mRNA levels had significantly shorter times before new tumors were detected (p = 0.03, p = 0.02, p = 0.003, and p = 0.08, respectively). Furthermore, older age diminished the association of mRNA levels with the appearance of subsequent tumors. Conclusions Our results show that levels of CD3ε, CD25, CD68, and ICAM-1 mRNA in BCC biopsies may predict risk for new BCC tumors.
Intramolecular Regulation of the Sequence-Specific mRNA Interferase Activity of MazF Fused to a MazE Fragment with a Linker Cleavable by Specific Proteases

ABSTRACT The genomes of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) consist of single-stranded RNA encoding polyproteins, which are processed to individual functional proteins by virus-encoded specific proteases. These proteases have been used as targets for drug development. Here, instead of targeting these proteases to inhibit viral infection, we utilized the protease activity to activate a toxic protein to prevent viral infection. We engineered the MazE-MazF antitoxin-toxin system of Escherichia coli to fuse a C-terminal 41-residue fragment of antitoxin MazE to the N-terminal end of toxin MazF with a linker having a specific protease cleavage site for either HIV PR (HIV-1 protease), NS3 protease (HCV protease), or factor Xa. These fusion proteins formed a stable dimer (instead of the MazF2-MazE2-MazF2 heterohexamer in nature) to inactivate the ACA (sequence)-specific mRNA interferase activity of MazF. When the fusion proteins were incubated with the corresponding proteases, the MazE fragment was cleaved from the fusion proteins, releasing active MazF, which then acted as an ACA-specific mRNA interferase cleaving single-stranded MS2 phage RNA. The intramolecular regulation of MazF toxicity by proteases as demonstrated may provide a novel approach for preventive and therapeutic treatments of infection by HIV-1, HCV, and other single-stranded RNA viruses.
The Athena-RC system for speech activity detection and speaker localization in the DIRHA smart home

We present our system for speech activity detection and speaker localization inside a smart home with multiple rooms equipped with microphone arrays of known geometry and placement. The smart home is developed as part of the DIRHA European funded project, providing both simulated and real data for system development and evaluation, under extremely challenging conditions of noise, reverberation, and speech overlap. Our proposed approach performs speech activity detection first, by employing multi-microphone decision fusion on traditional statistical models and acoustic features, within a Viterbi decoding framework, further assisted by signal energy- and model log-likelihood threshold-based heuristics. Then it performs speaker localization using traditional time-difference of arrival estimation between properly selected microphone pairs, further assisted by a dereverberation component. The system achieves very low detection errors, namely less than 4% (5%) for speech activity detection in the simulated (real) DIRHA corpus, and less than 10% (12%) for joint speech detection and speaker localization.
Energy-Efficient Geographic Routing in Environmentally Powered Wireless Sensor Networks

Current and potential applications of wireless sensor networks (WSNs) include military sensing, physical security, traffic surveillance, and environment monitoring, etc. Due to the fact that WSNs are composed of a large number of low-cost but energy constrained nodes, scalable and energy-efficient routing protocols are requisite for the WSN applications. In this paper, we study energy-efficient geographic routing protocols in environmentally powered WSNs, where the sensor nodes are capable of extracting energy from the environment. We propose a protocol, geographic energy-aware blacklisting routing with energy supply (GEBRES), which makes routing decision locally by jointly taking into account multiple factors-the realistic wireless channel condition, packets advancement to the destination, the energy availability on the node with environmental energy supply. Simulation results show that GEBRES is more energy efficient than the corresponding residual energy based protocols without considering the property of the energy changing (including recharging and consuming) rate. In particular, given the same energy and traffic models, GEBRES maintains higher minimum residual energy on nodes and achieves better load balancing in terms of having a smaller standard deviation of residual energy among nodes. GEBRES exhibits a little degradation on end-to-end delay, but does not compromise the end-to-end throughput performance
Validity of the bipolar spectrum in depression

1 Declaration. 2 Chapter 1: Introduction. 3 THE SCOPE OF MOOD DISORDERS . 3 A BRIEF REVIEW OF THE DEVELOPMENT OF MOOD DISORDER CLASSIFICATION. 4 Kraepelin & Bleuler. 5 The Unipolar/Bipolar distinction . 6 CURRENT CONCEPTS OF MOOD (AFFECTIVE) DISORDER . 6 Diagnostic categories . 6 Validity: External Criteria . 7 Point of Rarity. 8 Outcome Studies . 10 Endophenotypes. 10 Necessity and benefit of categories. 11 UTILITY: BOUNDARY DIFFICULTIES IN PRACTICE . 12 1. Poor sensitivity . 12 2. “False Unipolars”. 12 3. Uncertain Duration Threshold. 13 4. Mixed Episodes. 13 5. Antidepressant induced mania . 14 6. Abnormal personality traits. 14 SUMMARY . 15 THE BIPOLAR SPECTRUM . 15 Models . 16 Clinical Significance. 18 Differentiating Unipolar and Bipolar Spectrum Depression. 19 Neuropsychology. 19 Personality . 20 Genetics . 22 Clinical. 24 The Mood Disorder Questionnaire . 26 OUTLINE . 28 Chapter 2: A Prospective Clinical, Cognitive And Psychological Study . 29 INTRODUCTION. 29 METHOD . 30 Recruitment of participants . 30 Patients . 30 Controls . 30 Ethical Approval . 30 Eligibility Assessment . 31
A Bifunctional Enzyme That Has Both Monoacylglycerol Acyltransferase and Acyl Hydrolase Activities1[W][OA]

Monoacylglycerol acyltransferase (MGAT) catalyzes the synthesis of diacylglycerol, the precursor of triacylglycerol biosynthesis and an important signaling molecule. Here, we describe the isolation and characterization of the peanut (Arachis hypogaea) MGAT gene. The soluble enzyme utilizes invariant histidine-62 and aspartate-67 residues of the acyltransferase motif for its MGAT activity. A sequence analysis revealed the presence of a hydrolase (GXSXG) motif, and enzyme assays revealed the presence of monoacylglycerol (MAG) and lysophosphatidylcholine (LPC) hydrolytic activities, indicating the bifunctional nature of the enzyme. The overexpression of the MGAT gene in yeast (Saccharomyces cerevisiae) caused an increase in triacylglycerol accumulation. Similar to the peanut MGAT, the Arabidopsis (Arabidopsis thaliana) homolog (At1g52760) also exhibited both acyltransferase and hydrolase activities. Interestingly, the yeast homolog lacks the conserved HX4D motif, and it is deficient in the acyltransferase function but exhibits MAG and LPC hydrolase activities. This study demonstrates the presence of a soluble MGAT/hydrolase in plants. The predicted three-dimensional homology modeling and substrate docking suggested the presence of two separate substrate (MAG and LPC)-binding sites in a single polypeptide. Our study describes a soluble bifunctional enzyme that has both MGAT and hydrolase functions.
NMR imaging of changes in vascular morphology due to tumor angiogenesis

Tumor‐sprouted vessels are greater in both number and diameter in comparison to their healthy counterparts. A novel technique based on magnetic susceptibility contrast mechanisms that are sensitive to varying sizes of blood vessels is presented to measure differences between the relaxation rates (1/T2 and 1/T 2* ) in a rat glioma model and normal cerebral cortex. ΔR2 and ΔR2*, the differences between relaxation rates precontrast and postcontrast agent injection, were measured for an intravascular equilibrium contrast agent (MION) at various echo times. Since ΔR2*/ΔR2 increases as vessel size increases, this ratio can be used as a measure of the average vessel size within an ROI or a voxel. The stability and longevity of the contrast agent within the vasculature were verified (n = 2 trials), and the ratio of ΔR2*/ΔR2 between the tumor and normal cortex was measured to be 1.9 ± 0.2 (n = 4, echo time = 20 ms, and susceptibility difference (Δχ) ≈︁ 10−6). This ratio compared favorably to a predicted ratio determined using histologically determined vessel sizes and theoretical Monte Carlo modeling results (1.9 ± 0.1). Maps of the ratio of ΔR2*/ΔR2 were also made on a pixel‐by‐pixel basis. These techniques support the hypothesis that susceptibility contrast MRI can provide useful quantitative metrics of in vivo tumor vascular morphology.
Locus-Specific Biochemical Epigenetics/Chromatin Biochemistry by Insertional Chromatin Immunoprecipitation

Comprehensive understanding of regulation mechanisms of biological phenomena mediated by functions of genomic DNA requires identification of molecules bound to genomic regions of interest in vivo. However, nonbiased methods to identify molecules bound to specific genomic loci in vivo are limited. To perform biochemical and molecular biological analysis of specific genomic regions, we developed the insertional chromatin immunoprecipitation (iChIP) technology to purify the genomic regions of interest. We applied iChIP to direct identification of components of insulator complexes, which function as boundaries of chromatin domain, showing that it is feasible to directly identify proteins and RNA bound to a specific genomic region in vivo by using iChIP. In addition, recently, we succeeded in identifying proteins and genomic regions interacting with a single copy endogenous locus. In this paper, we will discuss the application of iChIP to epigenetics and chromatin research.
Hidden Markov Model for eye gaze prediction in networked video streaming

With the advent of eye gaze tracking technology, eye gaze is increasingly being used as a media interaction trigger in a variety of applications, such as eye typing, video content customization, and network video streaming based on region-of-interest (ROI). The reaction time of a gaze-based networked system, however, is in practice lower-bounded by the round trip time (RTT) of today's networks, which can be large. To improve the efficacy of gaze-based networked systems, in the paper we propose a Hidden Markov Model (HMM)-based gaze prediction strategy to predict future gaze locations to lower end-to-end reaction delay. We first design an HMM with three states corresponding to human's three major types of intrinsic eye movements. HMM parameters are obtained offline on a per-video basis during training phase. During testing phase, a window of noisy gaze observations are collected in real-time as input to a forward algorithm, which computes the most likely HMM state. Given the deduced HMM state, linear prediction is used to predict gaze location RTT seconds into the future. We demonstrate the applicability of our gaze prediction strategy by focusing on ROI-based bit allocation for network video streaming. To reduce transmission rate of a video stream without degrading viewer's perceived visual quality, we allocate more bits to encode the viewer's current spatial ROI, while devoting fewer bits in other spatial regions. The challenge lies in overcoming the delay between the time a viewer's ROI is detected by gaze tracking, to the time the effected video is encoded, delivered and displayed at the viewer's terminal. To this end, we use our proposed gaze-prediction strategy to predict future eye gaze locations, so that optimized bit allocation can be performed for future frames. Our experiments show that bit rate can be reduced by 21% without noticeable visual quality degradation when end-to-end network delay is as high as 200ms.
Dynamic Airline Revenue Management with Multiple Semi-Markov Demand

When a customer requests a discount fare, the airline must decide whether to sell the seat at the requested discount or to hold the seat in hope that a customer will arrive later who will pay more. We model this situation for a single-leg flight with multiple fare classes and customers who arrive according to a semi-Markov process (possibly nonhomogeneous). These customers can request multiple seats (batch requests) and can be overbooked. Under certain conditions, we show that the value function decreases as departure approaches. If each customer only requests a single seat or if the requests can be partially satisfied, then we show that there are optimal booking curves which decrease as departure approaches. We also provide counterexamples to show that this structural property of the optimal policy need not hold for more general arrival processes if the requests can be for more than one seat and must be accepted or rejected as a whole.
Impact of memory impairment on employment status in persons with systemic lupus erythematosus.

OBJECTIVE To assess the specific contribution of memory impairment to employment status in persons with systemic lupus erythematosus (SLE). METHODS A total of 832 patients with SLE were surveyed and data collected on demographics, SLE symptoms and activity, health status, depression, medications, health resource utilization, and current employment status. Participants underwent screening for memory impairment and based on their scores were categorized to 3 levels of memory function: intact, mild-moderate impairment, and severe impairment. Employment status was compared across impairment levels using multivariate logistic regression, adjusting for sociodemographic characteristics (i.e., age, sex, race, education, and marital status), employment status at year of diagnosis, disease activity, disease duration, and depression. RESULTS In the intact memory function group, 54.2% were employed, versus 40.6% in the mild-moderate impairment group and 31.0% in the severe impairment group. In the intact memory function group, 29.2% were unable to work, versus 40.6% in the mild-moderate impairment group and 56.3% in the severe impairment group. After multivariate adjustment, increasing levels of memory impairment predicted a decreased likelihood of being employed: odds ratio (OR) 0.70, 95% confidence interval (95% CI) 0.48-1.02 for the mild-moderate impairment group and OR 0.57, 95% CI 0.32-1.00 for the severe impairment group. Participants with memory impairment were more likely to report being unable to work: OR 1.36, 95% CI 0.90-2.04 for the mild-moderate impairment group, and OR 1.99, 95% CI 1.12-3.55 for the severe impairment group. These findings were statistically significant only in the severe impairment groups. CONCLUSION The findings suggest that severe memory impairment is an important factor associated with employment status in persons with SLE.
Amyloid fibril formation from crude protein mixtures

Amyloid fibrils have potential as bionanomaterials. A bottleneck in their commercial use is the cost of the highly purified protein typically needed as a starting material. Thus, an understanding of the role of heterogeneity in the mixtures from which amyloid fibrils are formed may inform production of these structures from readily available impure starting materials. Insulin, a very well understood amyloid‐forming protein, was modified by various reagents to explore whether amyloid fibrils could still form from a heterogeneous mixture of insulin derivatives. Aggregates were characterized by thioflavin T fluorescence and transmission electron microscopy. Using acetylation, reduction carboxymethylation, reduction pyridylethylation, trypsin digestion and chymotrypsin digestion, it was shown that amyloid fibrils can form from heterogeneous mixtures of modified insulin. The modifications changed both the rate of reaction and the yield of the final product, but led to fibrillar structures, some with interesting morphologies. Well defined, long, unbranched fibrils were observed in the crude reduced carboxymethylated insulin mixture and the crude reduced pyridylethylated insulin revealed the formation of “wavy” fibrils, compared with the straighter native insulin amyloid fibrils. Although trypsin digestion inhibited fibrils formation, chymotrypsin digestion of insulin produced a mixture of long and short fibrils under the same conditions. We conclude that amyloid fibrils may be successfully formed from heterogeneous mixtures and, further, that chemical modification may provide a simple means of manipulating protein fibril assembly for use in bionanotechnological applications, enabling some design of overall morphology in the bottom‐up assembly of higher order protein structures from amyloid fibrils. © 2011 American Institute of Chemical Engineers Biotechnol. Prog. , 2011
The Preliminary Study on Music?Movement Program developed for Stroke Patients

Purpose: This research with one group pre-post design was carried out to test the practical feasibility to administrate the Music Movement program developed for the stroke patients. Subjects: 12 stroke survivors at "J" Public Health Center in Seoul. were participated in. The average age was 68 years old, the ratio of sex was almost 5.8:4.2, the duration of was almost over 1 year. Method: Music Movement program was conducted for 2 hours 1day 6 weeks. The contents of Music Movement program were consisted of the preparatory activities, main activities and the wrap up activities. The preparatory activities are ice braking, greeting, explanation of the aims of music movement program, and introduction of stroke disease and ROM exercise. The main activities are the body motions with singing and playing musical instruments. The wrap up activities are stretching and joints and discussion of home activities. Data Collection: The outcome variables are muscle strength, finger pinch power, ROMs, flexibility, depression, and life satisfaction. Depression was measured by CES-D(Kim, I. J., 1999), life satisfaction by ladder scale(McDowell & Newell, 1996), and ADL state(Holbrook & Skilbeck, 1983). Data Analysis: SPSS/PC 10.0 for Window was used. Wilcoxon Signed Ranks Test was used to analyze outcome measures. The level of statistical significance was set at p
Class Extraction from the World Wide Web

In previous work we introduced KNOWITALL a data-driven, Web-based information extraction system. This paper focuses on the task of automatically extending the system’s initial ontology by extracting subclasses of given general classes and by discovering other closely related classes. We first show that the basic KNOWITALL model can be easily extended to accommodate high-precision subclass extraction (SE) and that subclass knowledge can lead to increases by a factor of 10 in the number of class instances extracted by KNOWITALL. Second, we introduce two methods that on average increase the number of subclasses extracted by the SE module itself by a factor of 3. Next, we show how the model can be extended to achieve high-quality related class extraction (RCE), which consists of discovering new classes closely related to the set of known classes. Of the classes discovered by KNOWITALL, in the test domains of Geography and Computers, 79.5% were bona-fide related classes.
Ninein is essential for the maintenance of the cortical progenitor character by anchoring the centrosome to microtubules

Summary The mammalian cerebral cortex develops from proliferative apical progenitor cells (APs) that exhibit cell cycle-dependent nuclear movement (interkinetic nuclear migration; INM), which may be important for efficient and continuous production of neurons. The Pax6 transcription factor plays a major role in INM by regulating various downstream molecules. We have previously observed abnormal INM and unstable localization of the centrosome in APs of the Pax6 homozygous mutant rat embryo. To understand the mechanisms of INM, we focused on the centrosomes of APs. One of the centrosomal proteins, ninein, is specifically localized in the centrosome of APs. We observed a dramatic downregulation of ninein in APs of the Pax6 mutant. Moreover, knockdown of ninein by RNAi induced ectopic distribution of reduced numbers of BrdU-positive (S-phase) and PH3-positive (M-phase) cells. Furthermore, time-lapsed imaging demonstrated that knockdown of ninein in vivo induced abnormal INM. Finally, we observed impaired microtubule regrowth in neural progenitors taken from Pax6 homozygous mutant rat embryos, which was recovered by via ninein overexpression. We also found that ninein knockdown enlarged the surface size area of apical endfeet of the APs. Our results suggest that ninein plays a role in the molecular machinery essential for INM by connecting microtubules to the centrosome.
Novel HIV-1 Recombinant Identified in a Foreign Heterosexual Resident in Japan: Relatedness to Recently Reported CRF69_01B, Detected Primarily among Japanese Men Who Have Sex with Men

ABSTRACT We report here an HIV-1 recombinant composed of CRF01_AE and subtype B, with a total of eight recombination breakpoints in the gag-pol and vpr-tat regions. This recombinant was identified from a Myanmarese heterosexual male in Japan and showed the chimera structure identical to recently reported CRF69_01B, detected primarily among men who have sex with men in Japan.