Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of the Basolateral and Apical Step of Transepithelial Organic Anion Secretion in Proximal Tubular Opossum Kidney Cells

The organic anion transport system in the proximal tubule of the kidney is of major importance for the excretion of a variety of endogenous and potentially toxic exogenous substances. Furthermore, the clearance of model substrates (e.g. para-aminohippurate) of this system is used for the determination of renal blood flow. We investigated regulation of organic anion secretion in a way that allowed us to examine simultaneously regulation of overall transepithelial secretion and to estimate the separate contributions of regulation of the basolateral and apical transport steps to this overall regulation. The data were verified by measurement of initial basolateral uptake rate and initial apical efflux rate. Opossum kidney cells were used as a suitable model system for proximal tubule cells, and [14C]para-aminohippurate was utilized as an organic anion. Stimulation of protein kinase C inhibited transepithelial secretion because of inhibition of both apical efflux and basolateral uptake. Inhibition of the mitogen-activated protein kinase (MAPK) kinase MEK reduced transepithelial secretion via inhibition of basolateral uptake and apical efflux. Epidermal growth factor (EGF) enhanced transepithelial secretion via stimulation of basolateral uptake but did not affect apical efflux. EGF induced stimulation of basolateral uptake was abolished by inhibition of MEK. EGF led to phosphorylation of ERK1/2, which was also abolished by inhibition of MEK. Thus, EGF stimulated basolateral uptake of organic anions via MAPKs. Transepithelial organic anion secretion can be regulated at two sites, at least: basolateral uptake and apical efflux. Both steps are under control of protein kinase C and MAPK. The pathophysiologically relevant growth factor EGF enhances transepithelial secretion via stimulation of basolateral uptake. EGF stimulates basolateral uptake via MEK and ERK1/2. Thus, renal organic anion extraction may be modulated, especially under pathophysiological conditions.
MLN4924 Is an Efficient Inhibitor of NEDD8 Conjugation in Plants1[C][W][OA]

The conjugation of the ubiquitin-like modifier NEURAL PRECURSOR CELL-EXPRESSED DEVELOPMENTALLY DOWN-REGULATED PROTEIN8/RELATED TO UBIQUITIN1 (NEDD8/RUB1; neddylation) is best known as an important posttranslational modification of the cullin subunits of cullin-RING-type E3 ubiquitin ligases (CRLs). MLN4924 has recently been described as an inhibitor of NEDD8-ACTIVATING ENZYME1 (NAE1) in human. Here, we show that MLN4924 is also an effective and specific inhibitor of NAE1 enzymes from Arabidopsis (Arabidopsis thaliana) and other plant species. We found that MLN4924-treated wild-type seedlings have phenotypes that are highly similar to phenotypes of mutants with a partial defect in neddylation and that such neddylation-defective mutants are hypersensitive to MLN4924 treatment. We further found that MLN4924 efficiently blocks the neddylation of cullins in Arabidopsis and that MLN4924 thereby interferes with the degradation of CRL substrates and their downstream responses. MLN4924 treatments also induce characteristic phenotypes in tomato (Solanum lycopersicum), Cardamine hirsuta, and Brachypodium distachyon. Interestingly, MLN4924 also blocks the neddylation of a number of other NEDD8-modified proteins. In summary, we show that MLN4924 is a versatile and specific neddylation inhibitor that will be a useful tool to examine the role of NEDD8- and CRL-dependent processes in a wide range of plant species.
The x-Kernel: An Architecture for Implementing Network Protocols

A description is given of an operating system kernel, called the x-Kernel, that provides an explicit architecture for constructing and composing network protocols. The authors' experience implementing and evaluation several protocols in the x-Kernel shows that this architecture is general enough to accommodate a wide range of protocols, yet efficient enough to perform competitively with less-structured operating systems. Experimental results demonstrating the architecture's generality and efficiency are provided. The explicit structure provided by the x-Kernel has the following advantages. First, the architecture simplifies the process of implementing protocols in the kernel, making it easier to build and test novel protocols. Second, the uniformity of the interface between protocols avoids the significant cost of changing abstractions and makes protocol performance predictable. Third, it is possible to write efficient protocols by tuning the underlying architecture rather than heavily optimizing protocols themselves. >
A small-molecule antivirulence agent for treating Clostridium difficile infection

A high-throughput screen against the Clostridium difficile toxin B cysteine protease domain identified a drug in clinical trials that reduced C. difficile pathology in a mouse model. A tough drug for a C. difficile problem Clostridium difficile infection (CDI) is an emerging disease threat caused by use of broad-spectrum antibiotics. CDI is the leading cause of hospital-acquired diarrhea, and with nearly half a million cases diagnosed in the United States each year, it places a yearly estimated burden of more than $4 billion on the U.S. healthcare system. A shift away from standard antibiotics is required to successfully contain this pathogen. Using a screen targeting bacterial virulence factors, Oresic Bender and colleagues identified a lead compound already in human clinical trials. The compound showed potent protective effects in a mouse model of CDI, supporting its translation into clinical studies as a new non-antibiotic treatment for CDI. Clostridium difficile infection (CDI) is a worldwide health threat that is typically triggered by the use of broad-spectrum antibiotics, which disrupt the natural gut microbiota and allow this Gram-positive anaerobic pathogen to thrive. The increased incidence and severity of disease coupled with decreased response, high recurrence rates, and emergence of multiple antibiotic-resistant strains have created an urgent need for new therapies. We describe pharmacological targeting of the cysteine protease domain (CPD) within the C. difficile major virulence factor toxin B (TcdB). Through a targeted screen with an activity-based probe for this protease domain, we identified a number of potent CPD inhibitors, including one bioactive compound, ebselen, which is currently in human clinical trials for a clinically unrelated indication. This drug showed activity against both major virulence factors, TcdA and TcdB, in biochemical and cell-based studies. Treatment in a mouse model of CDI that closely resembles the human infection confirmed a therapeutic benefit in the form of reduced disease pathology in host tissues that correlated with inhibition of the release of the toxic glucosyltransferase domain (GTD). Our results show that this non-antibiotic drug can modulate the pathology of disease and therefore could potentially be developed as a therapeutic for the treatment of CDI.
A Cross Structured Light Sensor and Stripe Segmentation Method for Visual Tracking of a Wall Climbing Robot

In non-destructive testing (NDT) of metal welds, weld line tracking is usually performed outdoors, where the structured light sources are always disturbed by various noises, such as sunlight, shadows, and reflections from the weld line surface. In this paper, we design a cross structured light (CSL) to detect the weld line and propose a robust laser stripe segmentation algorithm to overcome the noises in structured light images. An adaptive monochromatic space is applied to preprocess the image with ambient noises. In the monochromatic image, the laser stripe obtained is recovered as a multichannel signal by minimum entropy deconvolution. Lastly, the stripe centre points are extracted from the image. In experiments, the CSL sensor and the proposed algorithm are applied to guide a wall climbing robot inspecting the weld line of a wind power tower. The experimental results show that the CSL sensor can capture the 3D information of the welds with high accuracy, and the proposed algorithm contributes to the weld line inspection and the robot navigation.
Quantum Learning of Classical Stochastic Processes: The Completely-Positive Realization Problem

Among several tasks in Machine Learning, a specially important one is the problem of inferring the latent variables of a system and their causal relations with the observed behavior. A paradigmatic instance of this is the task of inferring the hidden Markov model underlying a given stochastic process. This is known as the positive realization problem (PRP), [L. Benvenuti and L. Farina, IEEE Trans. Autom. Control 49(5), 651–664 (2004)] and constitutes a central problem in machine learning. The PRP and its solutions have far-reaching consequences in many areas of systems and control theory, and is nowadays an important piece in the broad field of positive systems theory. We consider the scenario where the latent variables are quantum (i.e., quantum states of a finite-dimensional system) and the system dynamics is constrained only by physical transformations on the quantum system. The observable dynamics is then described by a quantum instrument, and the task is to determine which quantum instrument — if any — yields the process at hand by iterative application. We take as a starting point the theory of quasi-realizations, whence a description of the dynamics of the process is given in terms of linear maps on state vectors and probabilities are given by linear functionals on the state vectors. This description, despite its remarkable resemblance with the hidden Markov model, or the iterated quantum instrument, is however devoid of any stochastic or quantum mechanical interpretation, as said maps fail to satisfy any positivity conditions. The completely positive realization problem then consists in determining whether an equivalent quantum mechanical description of the same process exists. We generalize some key results of stochastic realization theory, and show that the problem has deep connections with operator systems theory, giving possible insight to the lifting problem in quotient operator systems. Our results have potential applications in quantum machine learning, device-independent characterization and reverse-engineering of stochastic processes and quantum processors, and more generally, of dynamical processes with quantum memory [M. Guţă, Phys. Rev. A 83(6), 062324 (2011); M. Guţă and N. Yamamoto, e-print arXiv:1303.3771(2013)].
Detection of rare and possibly carcinogenic human papillomavirus genotypes as single infections in invasive cervical cancer

The contribution of carcinogenic human papillomavirus (HPV) types to the burden of cervical cancer has been well established. However, the role and contribution of phylogenetically related HPV genotypes and rare variants remains uncertain. In a recent global study of 8977 HPV‐positive invasive cervical carcinomas (ICCs), the genotype remained unidentified in 3.7% by the HPV SPF10 PCR–DEIA–LiPA25 (version 1) algorithm. The 331 ICC specimens with unknown genotype were analysed by a novel sequence methodology, using multiple selected short regions in L1. This demonstrated HPV genotypes that have infrequently or never been detected in ICC, ie HPV26, 30, 61, 67, 68, 69, 73 and 82, and rare variants of HPV16, 18, 26, 30, 34, 39, 56, 67, 68, 69, 82 and 91. These are not identified individually by LiPA25 and only to some extent by other HPV genotyping assays. Most identified genotypes have a close phylogenetic relationship with established carcinogenic HPVs and have been classified as possibly carcinogenic by IARC. Except for HPV85, all genotypes in α‐species 5, 6, 7, 9 and 11 were encountered as single infections in ICCs. These species of established and possibly carcinogenic HPV types form an evolutionary clade. We have shown that the possibly carcinogenic types were detected only in squamous cell carcinomas, which were often keratinizing and diagnosed at a relatively higher mean age (55.3 years) than those associated with established carcinogenic types (50.9 years). The individual frequency of the possibly carcinogenic types in ICCs is low, but together they are associated with 2.25% of the 8338 included ICCs with a single HPV type. This fraction is greater than seven of the established carcinogenic types individually. This study provides evidence that possibly carcinogenic HPV types occur as single infections in invasive cervical cancer, strengthening the circumstantial evidence of a carcinogenic role. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Fast randomized algorithms for distributed edge coloring

Certain types of routing, scheduling and resource allocation problems in a distributed setting can be modeled as edge coloring problems. We present fast and simple randomized algorithms for edge coloring a graph, in the synchronous distributed point–to–point model of comput ation. Our algorithms compute an edge–coloring of a graph G with n nodes and maximum degree A with at most (1.6 + E)A + logz+d n colors with high probability (arbitrarily close to 1), for any fixed c, 6>0. To analyze the performance of our algorithms, we introduce new techniques for proving upper bounds on the tail probabilities of certain random variables. ChernoffHoeflding bounds are fundamental tools that are used very frequently in estimating tail probabilities. However, they assume stochastic independence among certain random variables, which may not always hold. Our results extend the Chernoff-Hoeffding bounds to certain types of random variables which are not stochastic ally independent. We believe that these results are of independent interest, and merit further study.
Does Wheat Genetically Modified for Disease Resistance Affect Root-Colonizing Pseudomonads and Arbuscular Mycorrhizal Fungi?

This study aimed to evaluate the impact of genetically modified (GM) wheat with introduced pm3b mildew resistance transgene, on two types of root-colonizing microorganisms, namely pseudomonads and arbuscular mycorrhizal fungi (AMF). Our investigations were carried out in field trials over three field seasons and at two locations. Serial dilution in selective King's B medium and microscopy were used to assess the abundance of cultivable pseudomonads and AMF, respectively. We developed a denaturing gradient gel electrophoresis (DGGE) method to characterize the diversity of the pqqC gene, which is involved in Pseudomonas phosphate solubilization. A major result was that in the first field season Pseudomonas abundances and diversity on roots of GM pm3b lines, but also on non-GM sister lines were different from those of the parental lines and conventional wheat cultivars. This indicates a strong effect of the procedures by which these plants were created, as GM and sister lines were generated via tissue cultures and propagated in the greenhouse. Moreover, Pseudomonas population sizes and DGGE profiles varied considerably between individual GM lines with different genomic locations of the pm3b transgene. At individual time points, differences in Pseudomonas and AMF accumulation between GM and control lines were detected, but they were not consistent and much less pronounced than differences detected between young and old plants, different conventional wheat cultivars or at different locations and field seasons. Thus, we conclude that impacts of GM wheat on plant-beneficial root-colonizing microorganisms are minor and not of ecological importance. The cultivation-independent pqqC-DGGE approach proved to be a useful tool for monitoring the dynamics of Pseudomonas populations in a wheat field and even sensitive enough for detecting population responses to altered plant physiology.
Neisseria gonorrhoeae Epithelial Cell Interaction Leads to the Activation of the Transcription Factors Nuclear Factor κB and Activator Protein 1 and the Induction of Inflammatory Cytokines

We have studied the effect of human bacterial pathogen Neisseria gonorrhoeae (Ngo) on the activation of nuclear factor (NF)-κB and the transcriptional activation of inflammatory cytokine genes upon infection of epithelial cells. During the course of infection, Ngo, the etiologic agent of gonorrhea, adheres to and penetrates mucosal epithelial cells. In vivo, localized gonococcal infections are often associated with a massive inflammatory response. We observed upregulation of several inflammatory cytokine messenger RNAs (mRNAs) and the release of the proteins in Ngo-infected epithelial cells. Moreover, infection with Ngo induced the formation of a NF-κB DNA–protein complex and, with a delay in time, the activation of activator protein 1, whereas basic leucine zipper transcription factors binding to the cAMP-responsive element or CAAT/enhancer-binding protein DNA-binding sites were not activated. In supershift assays using NF-κB–specific antibodies, we identified a NF-κB p50/p65 heterodimer. The NF-κB complex was formed within 10 min after infection and decreased 90 min after infection. Synthesis of tumor necrosis factor α and interluekin (IL)-1β occurred at later times and therefore did not account for NF-κB activation. An analysis of transiently transfected IL-6 promoter deletion constructs suggests that NF-κB plays a crucial role for the transcriptional activation of the IL-6 promoter upon Ngo infection. Inactivation of NF-κB conferred by the protease inhibitor N-tosyl-l-phenylalanine chloromethyl ketone inhibited mRNA upregulation of most, but not all, studied cyctokine genes. Activation of NF-κB and cytokine mRNA upregulation also occur in Ngo-infected epithelial cells that were treated with cytochalasin D, indicating an extracellular signaling induced before invasion.
The genetic and environmental relationship between major depression and the five-factor model of personality

Background Certain personality traits have long been suspected to reflect an enduring vulnerability to major depression (MD) in part because of shared genetic risk factors. Although many have agreed that normative personality is well captured by the ‘Big-Five’ personality traits of Openness (O), Conscientiousness (C), Extraversion (E), Agreeableness (A) and Neuroticism (N), to date genetically informative studies have only examined the relationship between MD and N and E. Method Questionnaires were completed on a website, yielding a sample of 44 112 subjects including both members of 542 same-sex twin pairs. Personality was measured by the Big Five Inventory. Structural modeling was performed by Mx. Results Three of the big-five personality traits – O, E and A – had small phenotypic associations with risk for MD and small genetic correlations. Two traits – N and C – had stronger phenotypic associations (positive for N and negative for C) with the following estimates of the genetic correlation with MD: +0.43 for N and −0.36 for C. N and C were moderately negatively correlated. Controlling for N reduced the genetic correlation between C and MD more than controlling for C reduced the genetic correlation between N and MD. Conclusions A large proportion of the genetic risk for MD that is expressed via personality is captured by N, with a modest amount due to C, and small amounts from O, E and A.
FUNDAMENTALS OF ROCK MECHANICS, SECOND EDITION

Chapters are included on: rock as a material; analysis of stress and infinitesimal strain; friction; elasticity and strength of rock; linear elasticity; laboratory testing; effects of size and stress gradient; fluid pressure and flow in rocks; behaviour in ductile materials; further problems in elasticity; time-dependent effects, crack phenomena and the mechanism of fracture; strain waves; the state of stress underground; underground measurements; granular materials; geological and geophysical applications; mining and other engineering applications. In the second edition, additions have been made in particular to the chapters on friction, elasticity and strength of rock, the state of stress underground, and geological and geophysical applications. The chapter on granular materials has undergone a major revision. /TRRL/
DBD––taxonomically broad transcription factor predictions: new content and functionality

DNA-binding domain (DBD) is a database of predicted sequence-specific DNA-binding transcription factors (TFs) for all publicly available proteomes. The proteomes have increased from 150 in the initial version of DBD to over 700 in the current version. All predicted TFs must contain a significant match to a hidden Markov model representing a sequence-specific DNA-binding domain family. Access to TF predictions is provided through http://transcriptionfactor.org, where new search options are now provided such as searching by gene names in model organisms, searching for all proteins in a particular DBD family and specific organism. We illustrate the application of this type of search facility by contrasting trends of DBD family occurrence throughout the tree of life, highlighting the clear partition between eukaryotic and prokaryotic DBD expansions. The website content has been expanded to include dedicated pages for each TF containing domain assignment details, gene names, links to external databases and links to TFs with similar domain arrangements. We compare the increase in number of predicted TFs with proteome size in eukaryotes and prokaryotes. Eukaryotes follow a slower rate of increase in TFs than prokaryotes, which could be due to the presence of splice variants or an increase in combinatorial control.
x-thalassaemia inCyprus1

SUMMARY Thefrequency ofox-thalassaemia inCyprus was determined withstudies ofhaemoglobin Bart's in1200GreekCypriot and132Turkish Cypriot newborn babies. OftheGreeknewborns, 12.4%,andoftheTurkish newborns, 6.8% hadraised HbBart's (from 0*6% to12.9% ofthetotal haemoglobin) suggesting thatthey were carriers ofeither o-thalassaemia-1 or oc-thalassaemia-2 genes.Thefindings suggest that thepopulation ofCyprus hasthehighest frequencies of o-thalassaemia among Caucasian people. Although haemoglobin H disease (thecompound heterozygous stateforoc-thalassaemia-1 and athalassaemia-2 genes)isfoundinalmostevery population intheMediterranean area, frequencies of oc-thalassaemia genesamongtheMediterranean people arerelatively low(Weatherall andClegg, 1972). Anexception tothis appears tobethepopulation ofCyprus inwhichhaemoglobin H disease has afrequency ofonecaseper200to500people (unpublished observations). A previous small survey of newborns hasprovided evidence thatthefrequency ofa-thalassaemia genes inthepopulation ofCyprus isoftheorder of10%(Ashiotis etal., 1973). The purpose ofthepresent study wastoobtain more accurate dataaboutthefrequency andthetypes of o-thalassaemia genes inthepopulation ofCyprus by measuring HbBart's inalarge numberofGreekand Turkish Cypriot newborns.
Compression via compressive sensing: A low-power framework for the telemonitoring of multi-channel physiological signals

Telehealth and wearable equipment can deliver personal healthcare and necessary treatment remotely. One major challenge is transmitting large amount of biosignals through wireless networks. The limited battery life calls for low-power data compressors. Compressive Sensing (CS) has proved to be a low-power compressor. In this study, we apply CS on the compression of multichannel biosignals. We firstly develop an efficient CS algorithm from the Block Sparse Bayesian Learning (BSBL) framework. It is based on a combination of the block sparse model and multiple measurement vector model. Experiments on real-life Fetal ECGs showed that the proposed algorithm has high fidelity and efficiency. Implemented in hardware, the proposed algorithm was compared to a Discrete Wavelet Transform (DWT) based algorithm, verifying the proposed one has low power consumption and occupies less computational resources.