Miracle-dz/UniFAR-FTUs huggingface dataset:
Catechol-O-Methyltransferase Inhibition Improves Set-Shifting Performance and Elevates Stimulated Dopamine Release in the Rat Prefrontal Cortex

The Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene affects activity of the enzyme and influences performance and efficiency of the prefrontal cortex (PFC); however, although catecholaminergic neurotransmission is implicated, the underlying mechanisms remain elusive because studies of the role of COMT in PFC function are sparse. This study investigated the effect of tolcapone, a brain-penetrant COMT inhibitor, on a rat model of attentional set shifting, which is dependent on catecholamines and the medial PFC (mPFC). Additionally, we investigated the effect of tolcapone on extracellular catecholamines in the mPFC using microdialysis in awake rats. Tolcapone significantly and specifically improved extradimensional (ED) set shifting. Tolcapone did not affect basal extracellular catecholamines, but significantly potentiated the increase in extracellular dopamine (DA) elicited by either local administration of the depolarizing agent potassium chloride or systemic administration of the antipsychotic agent clozapine. Although extracellular norepinephrine (NE) was also elevated by local depolarization and clozapine, the increase was not enhanced by tolcapone. We conclude that COMT activity specifically affects ED set shifting and is a significant modulator of mPFC DA but not NE under conditions of increased catecholaminergic transmission. These data suggest that the links between COMT activity and PFC function can be modeled in rats and may be specifically mediated by DA. The interaction between clozapine and tolcapone may have implications for the treatment of schizophrenia.
Full Professor University of Minho Portugal Software Tools for Understanding Grammatical Inference Algorithms : Part I – Tools for Regular Grammars and Finite-State Automata

Software demonstrators are effective tools to show and understand scientific and engineering concepts in function, and they also allow rapid experiments. In the field of grammatical inference, there is a lack of “ready-to-use” grammar synthesis tools, with simple interfaces showing intermediate stages of the grammar inference process, and the presented work addresses this issue by giving tools for experimentation with regular grammar and finite-state automata, to help students and researchers understand their properties, underlying concepts and applications.
IDENTIFICATION AND CHARACTERIZATION OF A FUNCTIONAL TATA BOX POLYMORPHISM OF THE UDP GLUCURONOSYLTRANSFERASE 1 A 7 GENE

UDP-glucuronosyltransferases (UGT) detoxify bilirubin and therapeutic drugs, a process influenced by single nucleotide polymorphisms (SNPs) in their structural genes and promoter elements. UGT1A1*28 is a functional UGT promoter polymorphism associated with Gilbert’s disease and severe irinotecan toxicity, which also occurs in the absence of UGT1A1*28. The aim of this study was to identify and characterize UGT promoter variants relevant for irinotecan detoxification. Recombinant UGT1A proteins were analyzed for irinotecan metabolite glucuronidation by UGT activity assays. In 427 healthy blood donors and 71 homozygous UGT1A1*28 carriers the 5’-untranslated region of the UGT1A7 gene locus was studied. A SNP was detected by allelic discrimination and characterized by reporter gene experiments. A novel –57 T>G SNP with a gene frequency of 0.39 in healthy blood donors was identified in the putative TATA box of the UGT1A7 gene reducing promoter activity to 30%. It is in linkage dysequilibrium with a variant of the UGT1A7 first exon present in the reduced activity UGT1A7*3 and UGT1A7*4 alleles. Homozygous UGT1A1*28 carriers simultaneously carried this variant in 98%. We identified a novel reduced function TATA box SNP of the UGT1A7 gene which catalyzes irinotecan metabolite detoxification. Its association with variants of the UGT1A1 promoter and UGT1A7 gene may influence irinotecan metabolism. Our finding emphasizes the importance of combinations of structural and regulatory gene polymorphisms which may be useful as a marker of drug toxicity. This article has not been copyedited and formatted. The final version may differ from this version. Molecular Pharmacology Fast Forward. Published on February 16, 2005 as DOI: 10.1124/mol.104. 007146 at A PE T Jornals on Jne 1, 2017 m oharm . aspeurnals.org D ow nladed from
Book Review: Detecting and modelling regional climate change

getting warmer. The emphasis is on the past being the key to the future, and looking at changing patterns of vulnerability. Chapter 3, which looks at  oods and weather-related hazards, would be a timely read for a student wishing to explore the extreme  ooding seen in continental Europe in the summer of 2002. Again, trends and contexts are well presented, as are summaries of key research papers. Chapter 4 examines landslides and environmental change. After reviewing the impact and types of landslides described, key concepts are illustrated by original case studies drawn from around the world. A sobering note of warning is struck by a consideration of the impact current environmental changes may have upon the worldwide rate of landslide occurrence. Chapter 5 explores the complex and challenging association of volcanic eruptions and environmental changes. A history of the research is presented, followed by several sections that examine key research areas. Volcanoes are discussed as agents of climatic change on a wide range of physical and temporal scales. In particular, the role of ‘super eruptions’ in initiating environmental change is reviewed, as are the roles of volcanic eruptions during the opening and closing phases of ice ages and mass extinctions. Chapter 6 focuses on sea-level change and associated natural hazards. Novel case studies considering this mechanism as an initiator of seismicity and perhaps volcanism are presented. The recently identi ed hazard of island collapse is also presented in adequate detail. Chapter 7 visits the new catastrophic mechanism, asteroid impacts, and examines this phenomenon and its potential in stimulating and critical detail. Chapter 8 is a very welcome review chapter, which packages the main themes of the book, looking in particular into the twenty- rst century. Throughout, the subject material is discussed in a stimulating and accessible way, and the research frontier for each topic is presented and discussed; there is no sense here that we are following a well-trodden path. Key theoretical concepts are dealt with in the context of each hazard discussed. In every chapter, key contemporary research is presented and summarized. All the chapters are well supported by an extensive bibliography of recently published research papers which will be readily accessible to the interested student, and this book is so stimulating that most students are going to be seeking more answers. Production values are high; clear diagrams, useful tables and well-de ned research summaries all serve to make this book a useful resource. Who should have this book on their shelves? Certainly, geology, Earth science and science geography students should own a copy, as should any academic teaching in this  eld. Make sure there are lots of copies on the library bookshelves, as no one will want to take it back!
Quantification of the Influence of Extracellular Laccase and Intracellular Reactions on the Isomer-Specific Biotransformation of the Xenoestrogen Technical Nonylphenol by the Aquatic Hyphomycete Clavariopsis aquatica

ABSTRACT The aquatic hyphomycete Clavariopsis aquatica was used to quantify the effects of extracellular laccase and intracellular reactions on the isomer-specific biotransformation of technical nonylphenol (t-NP). In laccase-producing cultures, maximal removal rates of t-NP and the isomer 4-(1-ethyl-1,4-dimethylpentyl)phenol (NP112) were about 1.6- and 2.4-fold higher, respectively, than in laccase-lacking cultures. The selective suppression of either laccase or intracellular reactions resulted in essentially comparable maximal removal rates for both compounds. Evidence for an unspecific oxidation of t-NP isomers was consistently obtained from laccase-expressing fungal cultures when intracellular biotransformation was suppressed and from reaction mixtures containing isolated laccase. This observation contrasts with the selective degradation of t-NP isomers by bacteria and should prevent the enrichment of highly estrogenic isomers in remaining t-NP. In contrast with laccase reactions, intracellular fungal biotransformation caused a significant shift in the isomeric composition of remaining t-NP. As a result, certain t-NP constituents related to more estrogenic isomers were less efficiently degraded than others. In contrast to bacterial degradation via ipso-hydroxylation, the substitution pattern of the quaternary α-carbon of t-NP isomers does not seem to be very important for intracellular transformation in C. aquatica. As-yet-unknown intracellular enzymes are obviously induced by nonylphenols. Mass spectral data of the metabolites resulting from the intracellular oxidation of t-NP, NP112, and 4-(1-ethyl-1,3-dimethylpentyl)phenol indicate nonyl chain hydroxylation, further oxidation into keto or aldehyde compounds, and the subsequent formation of carboxylic acid derivatives. Further metabolites suggest nonyl chain desaturation and methylation of carboxylic acids. The phenolic moieties of the nonylphenols remained unchanged.
Reputation-based multi-dimensional trust model in cloud manufacturing service platform

In previous researches of cloud manufacturing services, trust evaluation models were not flexible enough and subjective preferences of agents were not reflected either. For this issue, a five-dimensional trust evaluation system is built, and a reputation-based trust evaluation algorithm (RBTE) is also proposed. The direct trust rank (DT), friend reputation (RF) and platform reputation (RP) of the agent could be integrated into the trust rank (TR) with the weight vector through this algorithm. Combined with similarities of trust evaluation process, a trust network building approach is put forward in this research. The trust rank update algorithm also achieved dynamic rewards or punishments over time. Experimental results has shown good executing efficiency, and reflected the subjective preference of the transaction agent to a certain extent.
A model of the thermal processing of particles in solar nebula shocks: Application to the cooling rates of chondrules

Abstract— We present a model for the thermal processing of particles in shock waves typical of the solar nebula. This shock model improves on existing models in that the dissociation and recombination of H2 and the evaporation of particles are accounted for in their effects on the mass, momentum and energy fluxes. Also, besides thermal exchange with the gas and gas‐drag heating, particles can be heated by absorbing the thermal radiation emitted by other particles. The flow of radiation is calculated using the equations of radiative transfer in a slab geometry. We compute the thermal histories of particles as they encounter and pass through the shock.
Inferring intent in eye-based interfaces: tracing eye movements with process models

While current eye-based interfaces offer enormous potential forefficient human-computer interaction, they also manifest thedifficulty of inferring intent from user eye movements. This paperdescribes how fixation tracing facilitates the interpretation ofeye movements and improves the flexibility and usability ofeye-based interfaces. Fixation tracing uses hidden Markov models tomap user actions to the sequential predictions of a cognitiveprocess model. In a study of eye typing, results show that fixationtracing generates significantly more accurate interpretations thansimpler methods and allows for more flexibility in designing usableinterfaces. Implications for future research in eye-basedinterfaces and multimodal interfaces are discussed.
Simultaneous measurements of the charge, size, and shape of hydrometeors in an electrified cloud

With the use of an induction cylinder in conjunction with an optical array probe, simultaneous measurements were obtained of the size, shape, and charge of hydrometeors in a New Mexico thunderstorm, The particles with detectable charges (greater than 1–3 pC) were primarily graupel particles, and their charges are generally consistent with laboratory measurements of ice-ice collisional charging. The fraction with detectable charge increases with size, as does the magnitude of the mean charge. Also, the positively charged particles occur primarily at higher temperatures (> −22°C), and the degree of negative charging increases with decreasing temperature (down to −35°C).
Identification of c-myc as a Down-stream Target for Pituitary Tumor-transforming Gene*

Pituitary tumor-transforming gene (PTTG) encodes a protein implicated in cellular transformation and transcriptional regulation. To identify downstream target genes, I established cell lines with tightly regulated inducible expression of PTTG. DNA arrays were used to analyze gene expression profiles after PTTG induction. I identified c-myc oncogene as a major PTTGtarget. Induction of PTTG resulted in increased cell proliferation through activation of c-myc. I showed that PTTG activates c-myc transcription in transfected cells. PTTG binds to c-myc promoter near the transcription initiation site in a protein complex containing the upstream stimulatory factor (USF1). I have defined the PTTG DNA-binding site and mapped PTTG DNA binding domain to a region between amino acids 61 and 118. Furthermore, I demonstrated that PTTG DNA binding is required for its transcriptional activation function. These results definitively established the role of PTTG as a transcription activator and indicate that PTTG is involved in cellular transformation and tumorigenesis through activation of c-myc oncogene.
Spatiotemporal on-off intermittency by random driving.

Spatiotemporal on-off intermittency by random driving in spatially extended systems modeled by coupled map lattices is discussed. System size and coupling strength influence the onset of intermittency largely. At the onset, the temporal distribution of the laminar phase of one site still exhibits a power law with exponent -3/2 like that in a single map, while the spatial distribution displays a -1 power law with an exponential tail at large size for strong couplings.
ICH guidelines: inception, revision, and implications for drug development.

Since the inception of the International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) in 1990, six-party Expert Working Groups (EWG) have developed and revised numerous guidelines on preclinical safety evaluation (Table 1). The six parties to ICH represent the regulatory bodies and pharmaceutical manufacturing organizations in the three regions: Europe, Japan, and the United States, where the majority of new medicines are developed. The development of ICH guidelines is a stepwise process. In step 1, the EWG prepares a ‘‘final harmonized draft. ’’ Step 2 entails forwarding the draft to the Steering Committee for signature, which signifies acceptance for consultation. Step 3 is a process of consultation and discussion with regulatory organizations within the three regions and usually takes about 6 months or longer. Under step 3, the step 2 guideline is also released for public comments. Step 4 generates the Experts Document as a result of the consultation and is then submitted to the Steering Committee. Step 4 is reached when the Steering Committee endorses the adoption of the guideline by the regulatory bodies of the three regions. In the final step (step 5), the guidelines are incorporated into national or regional internal procedures, and the process is completed. The experience gained over the past decades, combined with the refined approaches for the generation of new drugs, has led to the recent ICH initiatives for developing new guidelines and revisiting some of the existing guidelines. The purpose of these initiatives is to optimize the scientific and technical aspects of the drug development process, ultimately accelerating the development of safe and effective medicines, while reducing animal use. The major ICH initiatives (bold in Table 1) include a new guideline, ICH S9, for preclinical evaluation of anticancer pharmaceuticals, an addendum to ICH S6 regarding preclinical safety evaluation of biologics, revision of ICH M3 which addresses the timing of preclinical studies in relation to various stages of clinical development, and a proposed new guideline on genotoxicity testing (ICH S2) that replaces and combines the ICH S2A and S2B. In this paper, we present the rationale behind these initiatives at ICH and some interpretation of the revised and new guidelines. We also provide commentary and perspective on the potential impact these new guidelines may have on preclinical safety evaluation programs.
A High-Speed Sense Amplifier Based Flip Flop with a Single Ended Latch Design and Low Voltage Operating Capabilities

This paper presents a sense amplifier-based flip flop (SAFF) with low power and high-speed operation capabilities. The power consumption and delay of FF improved after using the single-ended latch design. Contention and glitch-free operation are achieved through conditional cutoff. The study also shows a comparison of the modified SAFF with all previous flip-flops. The PDP of the modified SAFF improved to 60.7% compared to Jeong's SAFF, and the CK-Q delay improved to 44.6% compared to the MSFF. The modified SAFF provides operation even at very low voltages of 0.45 volts. The schematics of all SAFF are simulated using gdpk90nm technology in the Cadence Virtuoso tool.
Visualization of biomass solubilization and cellulose regeneration during ionic liquid pretreatment of switchgrass

Auto‐fluorescent mapping of plant cell walls was used to visualize cellulose and lignin in pristine switchgrass (Panicum virgatum) stems to determine the mechanisms of biomass dissolution during ionic liquid pretreatment. The addition of ground switchgrass to the ionic liquid 1‐n‐ethyl‐3‐methylimidazolium acetate resulted in the disruption and solubilization of the plant cell wall at mild temperatures. Swelling of the plant cell wall, attributed to disruption of inter‐ and intramolecular hydrogen bonding between cellulose fibrils and lignin, followed by complete dissolution of biomass, was observed without using imaging techniques that require staining, embedding, and processing of biomass. Subsequent cellulose regeneration via the addition of an anti‐solvent, such as water, was observed in situ and provided direct evidence of significant rejection of lignin from the recovered polysaccharides. This observation was confirmed by chemical analysis of the regenerated cellulose. In comparison to untreated biomass, ionic liquid pretreated biomass produces cellulose that is efficiently hydrolyzed with commercial cellulase cocktail with high sugar yields over a relatively short time interval. Biotechnol. Bioeng. 2009; 104: 68–75 Published 2009 Wiley Periodicals, Inc.
Mapas "geopolíticos" de internet: aplicación de las nuevas técnicas de representación de la información

Analizando los sitios web de universidades de diferentes paises es posible construir mapas que reflejen graficamente las relaciones que se establecen entre ellas, utilizando para ello nuevas tecnicas de representacion de la informacion como el analisis de cocitacion de sitios web (analisis de cositacion) y el escalamiento multidimensional (MDS). Pretendemos demostrar que estas relaciones no son ajenas al mundo real, y que siguen un patron politico, en lugar de un patron academico, permitiendonos construir autenticos “mapas geopoliticos” de Internet. Proponemos utilizar este tipo de representaciones como una herramienta para el analisis sociopolitico de la realidad, ya que con estos mapas obtenemos una instantanea de una region geografica y un momento determinados, de la que es posible extraer nueva y valiosa informacion. Palabras clave Sitios web de universidades; Tecnicas de representacion de la informacion; Webmetria; Escalamiento multidimensional; Analisis de cositacion; Mapas del conocimiento. “Geopolitical” maps of the Internet: Aplication of new information representation methods Abstract Based on university websites analysis, from different countries, we can build maps that show visual relations among them. We use new information representation methods, such as web site cocitation (cositation analisys) and multidimensional scaling (MDS). We try to demonstrate that these relations are closely tied to the ones established in the real world, and that they suit a political pattern instead an academical one, allowing us to generate Internet “geopolitical” maps. Our proposal is to use these kind of representations as tools for the social-political analisys of the real world environment. We can get a snapshot of a particular geographical region in a specific time, from wich we can get new and valuable information. Keywords University web sites; Information representation methods; Webometrics; Multidimensional Scaling; Cositation analisys; Knowledge maps.
8q24 prostate, breast, and colon cancer risk loci show tissue-specific long-range interaction with MYC

The 8q24 gene desert contains risk loci for multiple epithelial cancers, including colon, breast, and prostate. Recent evidence suggests these risk loci contain enhancers. In this study, data are presented showing that each risk locus bears epigenetic marks consistent with enhancer elements and forms a long-range chromatin loop with the MYC proto-oncogene located several hundred kilobases telomeric and that these interactions are tissue-specific. We therefore propose that the 8q24 risk loci operate through a common mechanism—as tissue-specific enhancers of MYC.
on Area Efficient CORDIC Algorithm and Reduction in Scale Factor

Supriya Aggarwal, Pramod K. Meher, and Kavita Khare proposed an area-time efficient CORDIC algorithm that completely eliminates the scale-factor by microrotation selection which is done by the most significant one detector in the micro rotation sequence generation circuit. Proper order of approximation of Taylor series is selected to meet the accuracy requirement, and the desired range of convergence is achieved. [1]. Francisco J. Jaime et al. proposed a new CORDIC algorithm, they show an enhanced version of the scaling-free CORDIC algorithm. Booth recoding algorithm is used to eliminate scaling and domain folding is avoided which reduces scaling to minimum but not eliminate it[2]. Leena Vachhani et al. proposed two areaefficient algorithms and their architectures based on CORDIC. Both the algorithms are applicable to the range of angles from 0 to 2 pi , and both the rotation and vectoring modes are used. Xilinx Spartan XC2S200E device is used and have the slice-delay products of about three. [3]. Koushik Maharatna et al. proposed a CORDIC rotator algorithm that which has the range of convergence from 0 to 2pi , and the target angle converges by executing appropriate iteration steps while keeping the scale factor virtually constant and completely predictable using the domain folding method. The IHP in-house 0.25m BiCMOS technology device is used on Synopsys' design analyzer and slice delay product of 26.98 is achieved[4].