Miracle-dz/UniFAR-FTUs huggingface dataset:
Product Inhibition of UDP-Glucuronosyltransferase (UGT) Enzymes by UDP Obfuscates the Inhibitory Effects of UGT Substrates

Substrates that are specific for certain UDP-glucuronosyltransferase (UGT) isoforms are usually used as specific inhibitors to identify UGT isoforms responsible for the glucuronidation of drugs. 1-Naphthol and 4-nitrophenol are probe substrates for human UGT1A6. In the present study, we found that UGT1A1-catalyzed estradiol 3-O-glucuronide formation and UGT1A4-catalyzed imipramine N-glucuronide formation in human liver microsomes were prominently decreased in the presence of 1-naphthol, but those by recombinant human UGT1A1 and UGT1A4, respectively, were not. Interestingly, when recombinant UGT1A6 was added in the reaction mixture, these activities by recombinant UGT1A1 and UGT1A4 were diminished in the presence of 1-naphthol. To interpret this phenomenon, the inhibitory effects of 1-naphthol O-glucuronide and UDP, products of the glucuronidation of 1-naphthol, were investigated. We found that UDP strongly inhibited the UGT1A1 (Ki = 7 μM) and UGT1A4 (Ki = 47 μM) activities in a competitive manner for the 5′-diphosphoglucuronic acid binding. These results suggest that UDP produced by UGT1A6-catalyzed 1-naphthol glucuronidation, but not 1-naphthol O-glucuronide and 1-naphthol per se, is the actual inhibition substance. Next, we examined the inhibitory effects of 15 compounds that are substrates of UGTs on estradiol 3-O-glucuronide formation in human liver microsomes compared with those by recombinant UGT1A1. Among them, 4 compounds (1-naphthol, 2-naphthol, 4-nitrophenol, and 4-methylumbelliferone) with high turnover rates (Vmax/Km value >200 μl/min/mg) showed more potent inhibition of the activity in human liver microsomes compared with that by the recombinant UGT1A1. Thus, we should pay attention to the inhibitory effects of UDP on UGT, which may cause erroneous evaluations in inhibition studies using human liver microsomes.
Online Retail Keyword Characteristics and Search Marketing Performance

To make judicious budget and resource allocation decisions, it is essential to understand the characteristics and performance of keywords used by target shoppers. Taking the approach of understanding consumers’ information needs, we construct a goal-related keyword characterization framework. Most search keywords exhibit more than one of the following characteristics - retailer specific, brand specific, product specific, feature related, or shopping intention. We analyze search engine ranking, click-through, and revenue data associated with visitor-disclosed search keywords from a top Web-only retailer over one year. Our findings show the interesting impacts of both keyword characteristics and dual-appearance of paid and organic advertisements on search marketing performance. The contributions of the research include a comprehensive search keyword characterization framework, and the analysis of the relationships between keyword characteristics and search performance. These findings have strong implications for search marketing decisions.
The Effect of Training Intensity on VO2max in Young Healthy Adults: A Meta-Regression and Meta-Analysis

Exercise training at a variety of intensities increases maximal oxygen uptake (VO2max), the strongest predictor of cardiovascular and all-cause mortality. The purpose of the present study was to perform a systematic review, meta-regression and meta-analysis of available literature to determine if a dose-response relationship exists between exercise intensity and training-induced increases in VO2max in young healthy adults. Twenty-eight studies involving human participants (Mean age: 23±1 yr; Mean VO2max: 3.4±0.8 l·min−1) were included in the meta-regression with exercise training intensity, session dose, baseline VO2max, and total training volume used as covariates. These studies were also divided into 3 tertiles based on intensity (tertile 1: ~60–70%; 2: ~80–92.5%; 3: ~100–250%VO2max), for comparison using separate meta-analyses. The fixed and random effects meta-regression models examining training intensity, session dose, baseline VO2max and total training volume was non-significant (Q4=1.36; p=0.85; R2=0.05). There was no significant difference between tertiles in mean change in VO2max (tertile 1:+0.29±0.15 l/min, ES (effect size) =0.77; 2:+0.26±0.10 l/min, ES=0.68; 3:+0.35±0.17 l/min, ES=0.80), despite significant (p<0.05) reductions in session dose and total training volume as training intensity increased. These data suggest that exercise training intensity has no effect on the magnitude of training-induced increases in maximal oxygen uptake in young healthy human participants, but similar adaptations can be achieved in low training doses at higher exercise intensities than higher training doses of lower intensity (endurance training).
Social Citizenship, Social Policy and Refugee Integration: a Case of Policy Divergence in Scotland?

Abstract The relationship between Holyrood and Westminster is an evolving one where there is some evidence of policy divergence. Underpinning policy approaches are different views of social citizenship, with the Holyrood approach maintaining elements of the post-1945 welfare settlement. The place of refugees and asylum seekers within these differing approaches is currently underexplored. This article looks at the Scottish and UK Governments’ views of social rights and how they apply to asylum seekers and refugees. It suggests that despite refugee ‘policy’ being at least partly reserved, the Scottish Government has been able to take a different approach from that of Westminster, an approach underpinned by these differing welfare outlooks.
Assessing Fifty Years of General Health Surveillance of Roe Deer in Switzerland: A Retrospective Analysis of Necropsy Reports

General wildlife health surveillance is a valuable source of information on the causes of mortality, disease susceptibility and pathology of the investigated hosts and it is considered to be an essential component of early warning systems. However, the representativeness of data from such surveillance programs is known to be limited by numerous biases. The roe deer (Capreolus capreolus capreolus) is the most abundant ungulate and a major game species all over Europe. Yet, internationally available literature on roe deer pathology is scarce. The aims of this study were (1) to provide an overview of the causes of mortality or morbidity observed in roe deer in Switzerland and to assess potential changes in the disease pattern over time; and (2) to evaluate the value and limitations of a long term dataset originating from general wildlife health surveillance. We compiled 1571 necropsy reports of free ranging roe deer examined at the Centre for Fish and Wildlife Health in Switzerland from 1958 to 2014. Descriptive data analysis was performed considering animal metadata, submitter, pathologist in charge, laboratory methods, morphological diagnoses and etiologies. Recurrent causes of mortality and disease pictures included pneumonia, diarrhea, meningoencephalitis, actinomycosis, blunt trauma, predation, neoplasms and anomalies. By contrast, other diagnoses such as fatal parasitic gastritis, suspected alimentary intoxication and reproductive disorders appeared only in earlier time periods. Diseases potentially relevant for other animals or humans such as caseous lymphadenitis (or pseudotuberculosis), salmonellosis, paratuberculosis and listeriosis were sporadically observed. The disease pattern in roe deer from Switzerland was largely in accordance with previous reports. The observed fluctuations were consistent with methodical and/or personnel changes and varying disease awareness. Nevertheless, despite such limitations, the compiled data provide a valuable baseline. To facilitate comparison among studies, we recommend systematically archiving all case documents and fixed tissues and to perform data analyses more regularly and in a harmonized way.
Abnormal Baroreflex Responses in Patients With Idiopathic Orthostatic Intolerance

Background—Patients diagnosed with idiopathic orthostatic intolerance report symptoms of lightheadedness, fatigue, and nausea accompanied by an exaggerated tachycardia when assuming the upright posture. Often, these symptoms are present in the absence of any decrease in arterial pressure. We hypothesized that patients with idiopathic orthostatic intolerance would have impaired cardiac vagal and integrated baroreflex function, lower blood volume, and increased venous compliance. Methods and Results—Sixteen patients and 14 healthy control subjects underwent the modified Oxford technique to assess cardiac vagal baroreflex sensitivity. Progressive lower-body negative pressure (to –50 mm Hg; LBNP) was used to examine the integrated baroreflex response to progressive hypovolemic stimuli. Blood volume and venous compliance were also assessed. Patients with idiopathic orthostatic intolerance had lower cardiac vagal baroreflex sensitivity (12±1 versus 25±4 ms/mm Hg;P ≤0.01). The integrated baroreflex response to low levels of LBNP was characterized by shorter R-R intervals and more symptoms such as lightheadedness, despite similar levels of blood pressure. There was a trend toward lower blood volume in the patient group (56±2 versus 63±3 mL/kg;P =0.054). Conclusions—Patients with idiopathic orthostatic intolerance have lower cardiac vagal baroreflex sensitivity and marginally lower blood volume and respond with faster heart rates despite similar levels of arterial pressure during LBNP. These findings may contribute to the exaggerated postural tachycardia and symptoms observed in patients with this disorder.
Transactional versus transformational leadership: An analysis of the MLQ.

A questionnaire used often to measure transformational, transactional and laissez-faire leadership is che Multifactor Leadership Questionnaire developed by Bass (Bass & Avolio, 1989). This study aims to test the factor structure of the MLQ as developed by Bass & Avolio. The MLQ-8Y was analysed using data collected in Dutch organizations. Seven hundred employees from eight organizations rated their leader's behaviour with the MLQ. First, an indication of the internal consistency of the scales developed by Bass is reported. The results of subsequent factor analyses show that the three types of leadership can be found in the data; however, the scales found here are slightly different from Bass' scales. Especially, the transactional and laissez-faire scales have been altered on theoretical and empirical grounds. The adapted version of the MLQ covers the domain with fewer items.
Defending Against DDoS Attacks in Bloom Filter based Multicasting

Bloom filter (BF) based forwarding is an effective approach to implement scalable multicasting in distributed systems. The forwarding BF carried by each packet can encode either multicast tree or destination IP addresses, which are termed as tree oriented approach (TOA) and destination oriented approach (DOA), respectively. Recent studies have indicated that TOA based protocols have serious vulnerabilities under some distributed denial-of-service (DDoS) attacks, and raised doubt about deployability of BF based multicasting. However, security analysis for DOA based protocols is still unavailable. In this paper, we present a systematic analysis of security performance of BF based multicasting. Important DDoS attacks and the corresponding defending mechanisms are studied in the context of DOA. We have positive findings that DOA, with convenient enhancement, has a robust performance in resisting a variety of DDoS attacks that can deny service of TOA based protocols. Moreover, we reveal that TOA based protocols are prone to flow duplication attack when applied in the data center network (DCN). We propose a dynamic-sized BF mechanism to defend against flow duplication attack for TOA based protocols in the DCN. Simulation results are presented to validate our theoretical analysis.
Protein Phylogenies and Signature Sequences: A Reappraisal of Evolutionary Relationships among Archaebacteria, Eubacteria, and Eukaryotes

SUMMARY The presence of shared conserved insertion or deletions (indels) in protein sequences is a special type of signature sequence that shows considerable promise for phylogenetic inference. An alternative model of microbial evolution based on the use of indels of conserved proteins and the morphological features of prokaryotic organisms is proposed. In this model, extant archaebacteria and gram-positive bacteria, which have a simple, single-layered cell wall structure, are termed monoderm prokaryotes. They are believed to be descended from the most primitive organisms. Evidence from indels supports the view that the archaebacteria probably evolved from gram-positive bacteria, and I suggest that this evolution occurred in response to antibiotic selection pressures. Evidence is presented that diderm prokaryotes (i.e., gram-negative bacteria), which have a bilayered cell wall, are derived from monoderm prokaryotes. Signature sequences in different proteins provide a means to define a number of different taxa within prokaryotes (namely, low G+C and high G+C gram-positive, Deinococcus-Thermus, cyanobacteria, chlamydia-cytophaga related, and two different groups of Proteobacteria) and to indicate how they evolved from a common ancestor. Based on phylogenetic information from indels in different protein sequences, it is hypothesized that all eukaryotes, including amitochondriate and aplastidic organisms, received major gene contributions from both an archaebacterium and a gram-negative eubacterium. In this model, the ancestral eukaryotic cell is a chimera that resulted from a unique fusion event between the two separate groups of prokaryotes followed by integration of their genomes.
A dynamic model of knowledge management for higher education development

Knowledge management (KM), an integrated approach used universally in knowledge intensive corporations, can maintain the competitive advantage for an organization in today's fast changing environment. However, many organizations are unable to get the results they expect when they introduce knowledge management into their organizational business processes. This paper suggests a dynamic model of knowledge management for higher education development, based on the analysis of many case studies of knowledge management in knowledge intensive organizations and the Monash task-based KM approach. This has been successfully implemented in recent years. The purpose of this model is to increase knowledge efficiency and to enhance organizational knowledge learning and sharing for discovery and innovation of new knowledge, which differentiates an organization from its competitors. This model includes six knowledge management activities for capturing, storing, sharing, learning, exploring, and exploiting knowledge related to a particular task. Based on the proposed model, this paper also highlights three factors of implementing knowledge management strategies: people, policy, and technology. Each factor has a different impact on the success of KM strategies. This paper proposes that KM is more than just the advantage of technology, intranet and Internet, but includes organizational issues, assumes information resource management together with the cultural change which is important in the KM implementation process. Finally, this paper suggests eighteen essential steps for the process leading to the effective knowledge management in a technological and knowledge intensive age
Left Ventricular Mass and Cardiovascular Reactivity in Young Men

The relation between left ventricular wall thickness and mass, arterial plasma catecholamines, and blood pressure at rest and during a mental arithmetic challenge and a cold pressor test was examined in 69 healthy men 19 years of age. The subjects were recruited from the 1st (n=21), 50th (n=26), and 99th (n=22) percentiles in mean blood pressure. All underwent echocardiography to determine mean wall thickness and left ventricular mass. Continuous intra-arterial blood pressure, electrocardiogram, and arterial sampling of plasma catecholamines were performed after 30 minutes of supine rest, during a 5-minute mental arithmetic challenge, and during a 1-minute cold pressor test. Stepwise multipleregression analyses considering mean wall thickness and left ventricular mass as the dependent variables were applied. Intra-arterial systolic blood pressure (r=.54, P<.0001) and arterial plasma epinephrine (r=.31, P=.009) after 30 minutes of supine rest were the only independent explanatory variables of mean wall thickness (multiple R2=.33, P<.0001). Blood pressure at screening and during mental stress and cold pressor tests were not independent explanatory variables. The present study suggests that resting arterial blood pressure and plasma epinephrine may be of importance for development of left ventricular hypertrophy.
A spatial model for the needle losses of pine‐trees in the forests of Baden‐Württemberg: an application of Bayesian structured additive regression

Summary. The data that are analysed are from a monitoring survey which was carried out in 1994 in the forests of Baden‐Württemberg, a federal state in the south‐western region of Germany. The survey is part of a large monitoring scheme that has been carried out since the 1980s at different spatial and temporal resolutions to observe the increase in forest damage. One indicator for tree vitality is tree defoliation, which is mainly caused by intrinsic factors, age and stand conditions, but also by biotic (e.g. insects) and abiotic stresses (e.g. industrial emissions). In the survey, needle loss of pine‐trees and many potential covariates are recorded at about 580 grid points of a 4 km × 4 km grid. The aim is to identify a set of predictors for needle loss and to investigate the relationships between the needle loss and the predictors. The response variable needle loss is recorded as a percentage in 5% steps estimated by eye using binoculars and categorized into healthy trees (10% or less), intermediate trees (10–25%) and damaged trees (25% or more). We use a Bayesian cumulative threshold model with non‐linear functions of continuous variables and a random effect for spatial heterogeneity. For both the non‐linear functions and the spatial random effect we use Bayesian versions of P‐splines as priors. Our method is novel in that it deals with several non‐standard data requirements: the ordinal response variable (the categorized version of needle loss), non‐linear effects of covariates, spatial heterogeneity and prediction with missing covariates. The model is a special case of models with a geoadditive or more generally structured additive predictor. Inference can be based on Markov chain Monte Carlo techniques or mixed model technology.
TRANSPORT POLICIES IN CENTRAL AND EASTERN EUROPE

The formerly socialist countries of Central and Eastern Europe have experienced profound political and economic changes since the demise of Communism in the late 1980s and early 1990s. Each country has its own particular history of transformation to a freer, more democratic, more market-based society. The timing and specific circumstances of the revolutions in each country vary. Even today, there are considerable differences among countries in the extent to which their political systems are fully democratic and how market-based their economies are. Thus, it is a bit risky to generalize about this group of diverse countries.
The context of scholarship of teaching and learning: identification and understanding of different microcultures

Scholarship of teaching and learning takes place in contexts. These contexts or microcultures in which the teachers perceive and practice teaching and learning are the focus of this paper. Taking our point of departure in the heuristic model of four types of microcultures (Roxå & Mårtensson, 2015) this paper seeks to investigate ways to identify and describe microcultures in a higher education organisation. By analysing the requests for obtaining licenses for an educational software program among teachers at the University of Southern Denmark we have identified two representatives of cultures with less or no dialogue on teaching matters and one representative of a dialogical culture. As a method of detecting other members of the microcultures at stake we use a snowball sampling method. The informants (12 in all) are interviewed through semi-structured interviews. Preliminary results from the interviews point to empirical differences among the microcultures in question. The representatives of the dialogical culture show a strong sense of community and describe a shared responsibility for the development of quality in their teaching. The representatives of the other microcultures describe their communication with colleagues as happening by coincidence and teaching seems to be an individual affair. The results point to a new way of identifying different microcultures. By using the requests for educational software licenses as an indicator for microcultural status we are able to learn more about different types of microcultures and thereby obtain a more nuanced knowledge of the contexts in which the scholarship of teaching and learning is to act in and upon.
catenin β requirements for developmentally distinct progenitors and have different Embryonic and fetal limb myogenic cells are derived from P < P

service Email alerting click here top right corner of the article or Receive free email alerts when new articles cite this article-sign up in the box at the object identifier (DOIs) and date of initial publication. by PubMed from initial publication. Citations to Advance online articles must include the digital publication). Advance online articles are citable and establish publication priority; they are indexed appeared in the paper journal (edited, typeset versions may be posted when available prior to final Advance online articles have been peer reviewed and accepted for publication but have not yet Vertebrate muscle arises sequentially from embryonic, fetal, and adult myoblasts. Although functionally distinct, it is unclear whether these myoblast classes develop from common or different progenitors. Pax3 and Pax7 are expressed by somitic myogenic progenitors and are critical myogenic determinants. To test the developmental origin of embryonic and fetal myogenic cells in the limb, we genetically labeled and ablated Pax3 + and Pax7 + cells. Pax3 + Pax7 À cells contribute to muscle and endothelium, establish and are required for embryonic myogenesis, and give rise to Pax7 + cells. Subsequently, Pax7 + cells give rise to and are required for fetal myogenesis. Thus, Pax3 + and Pax7 + cells contribute differentially to embryonic and fetal limb myogenesis. To investigate whether embryonic and fetal limb myogenic cells have different genetic requirements we conditionally inactivated or activated b-catenin, an important regulator of myogenesis, in Pax3-or Pax7-derived cells. b-Catenin is necessary within the somite for dermomyotome and myotome formation and delamination of limb myogenic progenitors. In the limb, b-catenin is not required for embryonic myoblast specification or myofiber differentiation but is critical for determining fetal progenitor number and myofiber number and type. Together, these studies demonstrate that limb embryonic and fetal myogenic cells develop from distinct, but related progenitors and have different cell-autonomous requirements for b-catenin. Supplemental material is available at http://www.genesdev.org. Muscle development, growth, and regeneration take place throughout vertebrate life and are mediated by myogenic progenitors. As with other stem cells, myo-genic progenitors are capable of self-renewal and differentiation. Therefore, a key to understanding vertebrate myogenesis is an understanding of the developmental origin of muscle progenitors and the signals that regulate their proliferation and differentiation. Vertebrate myogenesis occurs in three successive phases, fulfilling different functional needs (for review, see Stockdale 1992; Biressi et al. 2007a). Embryonic myogenesis establishes the basic muscle pattern. Fetal myogenesis is critical for …