Miracle-dz/UniFAR-FTUs huggingface dataset:
The Expression of Most Udp-glucuronosyltransferases (ugts) Is Increased Significantly during Caco-2 Cell Differentiation, While Ugt1a6 Is Highly Expressed Also in Undifferentiated Cells Dmd #22335 2 Running Title: Cell Differentiation and Ugts Expression in Caco-2 Caco-2 (wild Type) Cells Obtained f

The number of words in the Abstract: 249 The number of words in the Introduction (including refs.): 714 The number of words in the Discussion (including refs.): 1245 Abbreviations: UGT, UDP-glucuronosyltransferase; Caco-2, human intestinal cell line derived from colonic cancer; (q)RT-PCR, (quantitative) reverse transcriptase-polymerase chain reaction This article has not been copyedited and formatted. The final version may differ from this version. Abstract The human colon carcinoma cell line Caco-2 is often employed as a model for intestinal drug absorption. To better understand xenobiotics glucuronidation in Caco-2 cells, we have examined the expression levels of different UDP-glucuronosyltransferases (UGTs) in them. The effects of two main factors were investigated, namely passage number and cell differentiation. Hence, the mRNA levels of 15 human UGTs of subfamilies 1A and 2B were assessed in both undifferentiated and fully differentiated cells, at four passage levels, P31, P37, P43 and P49. Quantitative RT-PCR was employed to determine the mRNA levels of individual UGTs and the values were normalized using beta-actin as a reference gene. The results indicate that although passage number in the tested range exerts a mild effect on the expression level of several UGTs, the contribution of cell differentiation is much larger. The expression of nearly all the UGTs that were examined in this study was significantly, sometimes greatly, increased during cell differentiation. UGT1A6 was a distinct exception to this rule, however, since it was already highly expressed in the undifferentiated cells. The mRNA findings were confirmed at the enzyme activity level by measuring the glucuronidation of 1-naphthol, a very good substrate for UGT1A6, as well as estradiol that is not glucuronidated by this enzyme. The results revealed that 1-naphthol glucuronidation activity was high in both the differentiated and undifferentiated cells, whereas estradiol glucuronidation was only detected in the differentiated cells. Caco-2 cell differentiation, thus, plays a major role in UGTs expression and ensuing metabolic reactions. This article has not been copyedited and formatted. The final version may differ from this version. The epithelium of the intestinal mucosa is an important tissue for drug absorption due to its architecture and large surface area. Crossing the apical membrane of the cells lining the intestine exposes the orally administered drugs to the metabolic enzymes in these cells, namely intestinal first pass metabolism. In some cases drug metabolism in the intestine may differ considerably from the reactions that take place in the liver cells since several metabolic …
GIRAF: a method for fast search and flexible alignment of ligand binding interfaces in proteins at atomic resolution

Comparison and classification of protein structures are fundamental means to understand protein functions. Due to the computational difficulty and the ever-increasing amount of structural data, however, it is in general not feasible to perform exhaustive all-against-all structure comparisons necessary for comprehensive classifications. To efficiently handle such situations, we have previously proposed a method, now called GIRAF. We herein describe further improvements in the GIRAF protein structure search and alignment method. The GIRAF method achieves extremely efficient search of similar structures of ligand binding sites of proteins by exploiting database indexing of structural features of local coordinate frames. In addition, it produces refined atom-wise alignments by iterative applications of the Hungarian method to the bipartite graph defined for a pair of superimposed structures. By combining the refined alignments based on different local coordinate frames, it is made possible to align structures involving domain movements. We provide detailed accounts for the database design, the search and alignment algorithms as well as some benchmark results.
Potentiation of des-Arg9-Kallidin-Induced Vasoconstrictor Responses by Metallopeptidase Inhibition in Isolated Human Umbilical Artery

Several metallopeptidases have been reported to be involved in bradykinin (BK) B1 receptor agonist metabolism. Our goal was to evaluate in vitro roles of metallopeptidases [e.g., neutral endopeptidase (NEP), aminopeptidase M (APM), and angiotensin-converting enzyme (ACE)] as functional inactivators of the selective BKB1 receptor agonist Lys-des-Arg9-BK (DAKD) in isolated human umbilical artery (HUA) rings. Concentration-response curves (CRCs) to DAKD were performed after a 5-h incubation period. Treatment with 10 μM phosphoramidon (NEP inhibitor) or 10 μM amastatin (APM inhibitor) potentiated DAKD-elicited responses, whereas 1 μM captopril (ACE inhibitor) had no significant effects. However, when the three enzymes were simultaneously inhibited, a significant potentiation over responses obtained under concurrent NEP and aminopeptidase M inhibition was observed. In contrast, responses induced by the peptidase resistant BKB1 receptor agonist Sar-d-Phe8-des-Arg9-BK were not modified by triple peptidase inhibition. In addition, endothelial denudation failed to alter DAKD-induced responses in HUA. Finally, in the presence of NEP, ACE, and APM inhibition, Lys-des-Arg9-[Leu8]-BK, the potent BKB1 receptor antagonist, produced a parallel, concentration-dependent, rightward shift of DAKD CRCs. The obtained pKB (8.57) and the Schild slope not different from unity are in agreement with an interaction at a single homogeneous BKB1 receptor population. In summary, this work constitutes the first pharmacological evidence that metallopeptidases NEP, APM, and ACE represent a relevant inactivation mechanism of the endogenous BKB1 receptor agonist DAKD in isolated HUA.
Presentation a Neural Network with Gradual–Clustering Performance for Text Classification

So far, various methods have been used to classify text. One of the methods of text classification is using Artificial Neural Network (ANN). In this article, we have proposed and examined text classification with the proposed method of clustering neural network. The method of ANN is that, this network is composed of several sub networks (in this method, we consider each sub-network as a cluster which contains nodes and edges) with specific examples and unique models and they are interconnected step-by-step in order that the network be completed. For finding the pattern of subnetworks, the relationship between the inputs and outputs are put into consideration and the resulting pattern is generalized in sun-networks. When sub-networks are compounded together, regarding rules that they have learned, they have found the ability to create a similar output from the same inputs. The proposed system includes two phases: Learning and Test. The system in learning phase considers a set of training texts for extracting sub-network properties as to obtain the main features of each sub-network, while it uses these specific features of sub-network for classifying the uncategorized text in test phase. We have utilized two sets of data for our experiments: 1) 20-newsgroup; 2) Reuters 21578. The experimental obtained results show that our proposed method can extend text classification, at its best to 92%.
Spiral‐in/out BOLD fMRI for increased SNR and reduced susceptibility artifacts

BOLD fMRI is hampered by dropout of signal in the orbitofrontal and parietal brain regions due to magnetic field gradients near air‐tissue interfaces. This work reports the use of spiral‐in trajectories that begin at the edge of k‐space and end at the origin, and spiral in/out trajectories in which a spiral‐in readout is followed by a conventional spiral‐out trajectory. The spiral‐in trajectory reduces the dropout and increases the BOLD contrast. The spiral‐in and spiral‐out images can be combined in several ways to simultaneously achieve increased signal‐to‐noise ratio (SNR) and reduced dropout artifacts. Activation experiments employing an olfaction task demonstrate significantly increased activation volumes due to reduced dropout, and overall increased SNR in all regions. Magn Reson Med 46:515–522, 2001. © 2001 Wiley‐Liss, Inc.
Effect of Sparse Long-chain Branching on the Film-casting Behavior for a Series of Well-defined HDPEs

Abstract The effect of sparse long chain branching, LCB, on the film-casting process is analyzed using a molecular model for the rheological behavior for a series of well-characterized, high-density polyethylene (HDPE) resins and a low-density polyethylene (LDPE) resin at various drawdown ratios. A full rheological characterization in both shear and shear-free flows is also presented. At low drawdown ratios, the LDPE exhibited the least degree of necking at distances less than the HDPE frostline. The sparsely-branched HDPE resins films had similar final film-widths that were larger than those of the linear HDPE. As the drawdown ratio was increased, film width profiles separated based on branching level. Small amounts of LCB were found to reduce the amount of necking at intermediate drawdown ratios. At higher drawdown ratios, the sparsely-branched HDPE resins of lower LCB content had film-widths that mimicked that of the linear HDPE, while the sparsely-branched HDPE resins of higher LCB content retained a larger film width. Molecular structural analysis via the Pom-Pom constitutive model suggested that branching that was distributed across a larger range of backbone lengths served to improve resistance to necking. As the drawdown ratio increased, the length of the backbones dominating the response decreased, so that the linear chains were controlling the necking behavior of the sparsely-branched resins of lower LCB content while remaining in the branched regime for higher LCB content HDPEs. Other processing variables such as shear viscosity magnitude, extrudate swell, and non-isothermal processing conditions were eliminated as contributing factors to the differences in the film width profile.
Biological Significance of Photoreceptor Photocycle Length: VIVID Photocycle Governs the Dynamic VIVID-White Collar Complex Pool Mediating Photo-adaptation and Response to Changes in Light Intensity

Most organisms on earth sense light through the use of chromophore-bearing photoreceptive proteins with distinct and characteristic photocycle lengths, yet the biological significance of this adduct decay length is neither understood nor has been tested. In the filamentous fungus Neurospora crassa VIVID (VVD) is a critical player in the process of photoadaptation, the attenuation of light-induced responses and the ability to maintain photosensitivity in response to changing light intensities. Detailed in vitro analysis of the photochemistry of the blue light sensing, FAD binding, LOV domain of VVD has revealed residues around the site of photo-adduct formation that influence the stability of the adduct state (light state), that is, altering the photocycle length. We have examined the biological significance of VVD photocycle length to photoadaptation and report that a double substitution mutant (vvdI74VI85V), previously shown to have a very fast light to dark state reversion in vitro, shows significantly reduced interaction with the White Collar Complex (WCC) resulting in a substantial photoadaptation defect. This reduced interaction impacts photoreceptor transcription factor WHITE COLLAR-1 (WC-1) protein stability when N. crassa is exposed to light: The fast-reverting mutant VVD is unable to form a dynamic VVD-WCC pool of the size required for photoadaptation as assayed both by attenuation of gene expression and the ability to respond to increasing light intensity. Additionally, transcription of the clock gene frequency (frq) is sensitive to changing light intensity in a wild-type strain but not in the fast photo-reversion mutant indicating that the establishment of this dynamic VVD-WCC pool is essential in general photobiology and circadian biology. Thus, VVD photocycle length appears sculpted to establish a VVD-WCC reservoir of sufficient size to sustain photoadaptation while maintaining sensitivity to changing light intensity. The great diversity in photocycle kinetics among photoreceptors may be viewed as reflecting adaptive responses to specific and salient tasks required by organisms to respond to different photic environments.
Simulation studies of carbon nanotube field-effect transistors

Simulation studies of carbon nanotube field-effect transistors (CNFETs) are presented using models of increasing rigour and versatility that have been systematically developed. Firstly, it is demonstrated how one may compute the standard tight-binding band structure. From this foundation, a self-consistent solution for computing the equilibrium energy band diagram of devices with Schottkybarrier source and drain contacts is developed. While this does provide insight into the likely behaviour of CNFETs, a non-equilibrium model is required in order to predict the current-voltage relation. To this end, the effective-mass approximation is utilized, where a parabolic fit to the band structure is used in order to develop a Schrödinger-Poisson solver. This model is employed to predict both DC behaviour and switching times for CNFETs, and was one of the first models that captured quantum effects, such as tunneling and resonance, in these devices. In addition, this model has been used in order to validate compact models that incorporated tunneling via the WKB approximation. A modified WKB derivation is provided in order to account for the non-zero reflection of carriers above a potential energy step. In order to allow for greater flexibility in the CNFET geometries, and to lift the effective-mass approximation, a non-equilibrium Green’s function method is finally developed, which uses an atomistic tight-binding Hamiltonian to model doped-contact, as opposed to Schottky-barrier-contact, devices. This approach benefits by being able to account for both interand intra-band tunneling, and by utilizing a quadratic matrix equation in order to improve the computation time for the required self-energy matrices. Within this technique, an expression for the local inter-atomic current is derived in order to provide more detailed information than the usual compact expression for the terminal current. With this final model, an investigation is presented into the effects of geometrical variations, contact thicknesses, and azimuthal variation in the surface potential of the nanotube.
Periprocedural effects of statins on the incidence of contrast-induced acute kidney injury: a systematic review and meta-analysis of randomized controlled trials

Abstract Background: The reports on the efficacy of statins for the prevention of contrast-induced acute kidney injury (CIAKI) remain controversial. The objective of this meta-analysis was to assess the effect of statins for the prevention of CIAKI. Methods: Comprehensive literature searches for randomized controlled trials (RCTs) of periprocedural statin treatment for prevention of CIAKI were performed using MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials Systematic Reviews and clinicaltrials.gov from inception until May 2014. The primary outcome was the incidence of CIAKI. Results: Thirteen prospective RCTs were included in our analysis. Of 5803 patients with contrast exposures, 304 patients (5.2%) had CIAKI. Patients in the statin group had an overall lower incidence of CIAKI (3.6%) compared to the control group (6.9%). Intravenous (IV) fluid hydration was used in both groups of all included studies for prevention of CIAKI. There was a significant protective effect of periprocedural statins on the incidence of CIAKI when compared to the control group [risk ratios (RRs): 0.49; 95% CI: 0.37–0.66, I2 of 25%]. Conclusions: Our study demonstrates a statistically significant protective effect of statin treatment during procedures with contrast exposures. This finding suggests the use of statins in addition to standard IV crystalloid hydration may be beneficial in the prevention of CIAKI.
Satellite DNAs are conserved and differentially transcribed among Gryllus cricket species

Abstract Satellite DNA (satDNA) is an abundant class of non-coding repetitive DNA that is preferentially found as tandemly repeated arrays in gene-poor heterochromatin but is also present in gene-rich euchromatin. Here, we used DNA- and RNA-seq from Gryllus assimilis to address the content and transcriptional patterns of satDNAs. We also mapped RNA-seq libraries for other Gryllus species against the satDNAs found in G. assimilis and G. bimaculatus genomes to investigate their evolutionary conservation and transcriptional profiles in Gryllus. Through DNA-seq read clustering analysis using RepeatExplorer, dotplots analysis and fluorescence in situ hybridization mapping, we found that ∼4% of the G. assimilis genome is represented by 11 well-defined A + T-rich satDNA families. These are mainly located in heterochromatic areas, with some repeats able to form high-order repeat structures. By in silico transcriptional analysis we identified satDNAs that are conserved in Gryllus but differentially transcribed. The data regarding satDNA presence in G. assimilis genome were discussed in an evolutionary context, with transcriptional data enabling comparisons between sexes and across tissues when possible. We discuss hypotheses for the conservation and transcription of satDNAs in Gryllus, which might result from their role in sexual differentiation at the chromatin level, heterochromatin formation and centromeric function.
Example-based grapheme-to-phoneme conversion for Thai

Several characteristics of the Thai writing system make Thai grapheme-to-phoneme (G2P) conversion very challenging. In this paper, we propose an Example-Based Grapheme-toPhoneme conversion approach. It generates the pronunciation of a word by selecting, modifying and combining pronunciations from syllables from training corpus. The best system achieves 80.99% word accuracy and 94.19% phone accuracy which significantly outperform previous approaches for Thai. Index Terms: Thai, grapheme-to-phoneme conversion, example-based, letter-to-sound rules, pronunciation
Resource allocation in the grid using reinforcement learning

In this paper we study a minimalist decentralized algorithm for resource allocation in a simplified Grid-like environment. We consider a system consisting of large number of heterogenous reinforcement learning agents that share common resources for their computational needs. There is no communication between the agents: the only information that agents receive is the (expected) completion time of a job it submitted to a particular resource and which serves as a reinforcement signal for the agent. The results of our experiments suggest that reinforcement learning can be used to improve the quality of resource allocation in large scale heterogenous system.
An empirical account of the relation between discourse structure and pauses in Portuguese

The work reported in this paper is part of a project that aims at describing the role of prosody in conveying discourse structure in European Portuguese. We conducted an empirical study to investigate whether the organization of discourse could be reflected by the occurrence of pauses. In order to achieve that, we started by asking sixteen subjects to annotate two texts using two discourse segmentation methods: Grosz and Sidner’s, and Passonneau and Litman’s. We then confronted the segmentation obtained with pause distribution and length. We also verified which of the two methods can produce segmentation closer to pause occurrence. The results obtained are still provisional, but they at least show that the longest pauses are associated with the strongest discourse breaks.
Reconstitution of a protein monolayer on thiolates functionalized gaas surface

In the aim to realize an efficient resonant biosensor, gallium arsenide (GaAs) presents many advantages. In addition to its properties of transduction, GaAs is a crystal for which microfabrication processes were developed, conferring the possibility to miniaturize the device and integrate electronic circuit. Moreover, the biofunctionalization could be realized on the crystalline surface without layer deposition, constituting a real advantage to perform reusable sensor. The functionalization of GaAs surface was engaged in order to immobilize a protein monolayer on this substrate. Functionalization was done using a mixed self assembled monolayer of thiolate molecules. Characterizations at micro and nanoscale were performed to control the surface state, the establishment of thiolates self-assembled monolayer, the surface atomic composition and the topography of the GaAs substrate at the different steps of the process. Protein immobilization on thiolates modified GaAs was revealed through a detailed AFM study and in situ MALDI-TOF MS and MS/MS modified surface interrogations.
Digitized by the Internet Archive in 2011 with Funding from on the Optimal Timing of Benefits with Heterogeneous Workers and Human Capital Depreciation Human Capital Depreciation*

This paper studies the optimal timing of unemployment insurance subsidies in a McCall search model. Risk-averse workers sequentially sample random job opportunities. Our model distinguishes unemployment subsidies from consumption during unemployment by allowing workers to save and borrow freely. When the insurance agency faces a group of homogeneous workers solving stationary search problems, the optimal subsidies are independent of unemployment duration. In contrast, when workers are heterogeneous or when human capital depreciates during the spell, the optimal subsidy is no longer constant. We explore the main determinants of the shape of the optimal subsidy schedule, isolating forces for subsidies to optimally rise or fall with duration.
Low-Level Contrast Statistics of Natural Images Can Modulate the Frequency of Event-Related Potentials (ERP) in Humans

Humans are fast and accurate in categorizing complex natural images. It is, however, unclear what features of visual information are exploited by brain to perceive the images with such speed and accuracy. It has been shown that low-level contrast statistics of natural scenes can explain the variance of amplitude of event-related potentials (ERP) in response to rapidly presented images. In this study, we investigated the effect of these statistics on frequency content of ERPs. We recorded ERPs from human subjects, while they viewed natural images each presented for 70 ms. Our results showed that Weibull contrast statistics, as a biologically plausible model, explained the variance of ERPs the best, compared to other image statistics that we assessed. Our time-frequency analysis revealed a significant correlation between these statistics and ERPs' power within theta frequency band (~3–7 Hz). This is interesting, as theta band is believed to be involved in context updating and semantic encoding. This correlation became significant at ~110 ms after stimulus onset, and peaked at 138 ms. Our results show that not only the amplitude but also the frequency of neural responses can be modulated with low-level contrast statistics of natural images and highlights their potential role in scene perception.