Miracle-dz/UniFAR-FTUs huggingface dataset:
Substrate selectivity of human intestinal UDP-glucuronosyltransferases (UGTs): in silico and in vitro insights

Abstract The current drug development process aims to produce safe, effective drugs within a reasonable time and at a reasonable cost. Phase II metabolism (glucuronidation) can affect drug action and pharmacokinetics to a considerable extent and so its studies and prediction at initial stages of drug development are very imperative. Extensive glucuronidation is an obstacle to oral bioavailability because the first-pass glucuronidation [or premature clearance by UDP-glucuronosyltransferases (UGTs)] of orally administered agents frequently results in poor oral bioavailability and lack of efficacy. Modeling of new chemical entities/drugs for UGTs and their kinetic data can be useful in understanding the binding patterns to be used in the design of better molecules. This review concentrates on first-pass glucuronidation by intestinal UGTs, including their topology, expression profile, and pharmacogenomics. In addition, recent advances are discussed with respect to substrate selectivity at the binding pocket, structural requirements, and mechanism of enzyme actions.
A Model-Based Method for Assessing Insulin Sensitivity From the Oral Glucose Tolerance Test. Diabetes Care 2001;24:539–548

OBJECTIVE Available insulin sensitivity (IS) methods based on the oral glucose tolerance test (OGTT) are empirical. We used a glucose-insulin model to derive an OGTT-based IS (oral glucose insulin sensitivity [OGIS]) index, which predicts glucose clearance in a glucose clamp. We validated OGIS against clamp data. RESEARCH DESIGN AND METHODS OGIS requires glucose and insulin concentrations from a 75-g OGTT at 0, 2, and 3 h (3-h OGTT) or at 0, 1.5, and 2 h (2-h OGTT). The formula includes six constants optimized to match the clamp results. For this purpose, 15 lean nondiabetic subjects (BMI < 25 kg/m2), 38 obese nondiabetic subjects (BMI > 25 kg/m2), and 38 subjects with type 2 diabetes randomly underwent an OGTT and a 120 mU x min(-1) x m(-2) insulin infusion euglycemic clamp. Glucose clearance (Cl CLAMP), calculated as the ratio of glucose infusion to concentration during the last hour of the clamp, was compared with OGIS. OGIS was also tested on an independent group of 13 subjects with impaired glucose tolerance (IGT). RESULTS OGIS and Cl CLAMP were correlated in the whole group (R = 0.77, P < 0.0001), in the subgroups (lean: R = 0.59; obese: R = 0.73; type 2 diabetes: R = 0.49; P < 0.02), and in the independent IGT group (R = 0.65, P < 0.02). Reproducibility of OGIS and Cl CLAMP were similar (coefficients of variation: OGIS 7.1%, Cl CLAMP 6.4%). OGIS was as effective as Cl CLAMP in discriminating between groups (for OGIS, lean vs. obese: 440 +/- 16 vs. 362 +/- 11 ml x min(-1) x m(-2), p < 0.001; lean vs. type 2 diabetes: 440 +/- 16 vs. 239 +/- 7, P < 0.0001; obese vs. type 2 diabetes: 362 +/- 11 vs. 239 +/- 7, P < 0.0001; results were similar for Cl CLAMP). The relationships between IS and BMI, fasting plasma insulin, and insulin secretion (calculated from the OGTT insulin concentration) were examined. OGIS yielded results similar to Cl CLAMP and fully consistent with established physiological principles. The performance of the index for the 3-h and 2-h OGTT was similar. CONCLUSIONS OGIS is an index of IS in good agreement with the clamp. Because of its simplicity (only three blood samples required), this method has potential use for clinical investigation including large-scale epidemiological studies.
A Fast Relaxed Normal Two Split Method and an Effective Weighted TV Approach for Euler's Elastica Image Inpainting

This paper proposes two numerical algorithms for solving Euler's elastica-based inpainting model. The minimizing functional is nonsmooth and nonconvex and involves high-order derivatives, that traditional gradient descent based methods converge very slowly. Recent alternating minimization methods show fast convergence when a good choice of parameters is used. The objective of this paper is to introduce efficient algorithms which have simple structures with fewer parameters. These methods are based on operator splitting and alternating direction method of multipliers, and subproblems can be solved efficiently by Fourier transforms and shrinkage operators. For the first method, we relax the normal vector in the curvature term of the Euler's elastica model and exploit two operator splitting techniques to propose a Relaxed Normal Two Split (RN2Split) method. The second method, $\kappa$-weighted Total Variation ($\kappa$TV), solves the Euler's elastica minimization problem as a weighted total variation. We pre.
Statistical Parsing of Spanish and Data Driven Lemmatization

Although parsing performances have greatly improved in the last years, grammar inference from treebanks for morphologically rich lan- guages, especially from small treebanks, is still a challenging task. In this paper we in- vestigate how state-of-the-art parsing perfor- mances can be achieved on Spanish, a lan- guage with a rich verbal morphology, with a non-lexicalized parser trained on a treebank containing only around 2,800 trees. We rely on accurate part-of-speech tagging and data- driven lemmatization in order to cope with lexical data sparseness. Providing state-of- the-art results on Spanish, our methodology is applicable to other languages.
A Limiting Property of the Matrix Exponential

A limiting property of the matrix exponential is proven: if the (1,1)-block of a 2-by-2 block matrix becomes “arbitrarily small” in a limiting process, the matrix exponential of that matrix tends to zero in the (1,1)-, (1,2)-, and (2,1)-blocks. The limiting process is such that either the log norm of the (1,1)-block goes to negative infinity, or, for a certain polynomial dependency, the matrix associated with the largest power of the variable that tends to infinity is stable. The limiting property is useful for simplification of dynamic systems that exhibit modes with sufficiently different time scales. The obtained limit then implies the decoupling of the corresponding dynamics.
A degenerated equivalent circuit model and hybrid prediction for state-of-health (SOH) of PEM fuel cell

The 2014 IEEE PHM data challenge problem deals with the state-of-health (SOH) of proton exchange membrane fuel cell (PEMFC) given two degradation data sets: (i) a reference data set (FC1) operated under constant current is fully given until 991 h and (ii) a test data set (FC2) operated under rippled current is partially given until 550h. The proposed research aims at predicting the SOH (or EIS spectra) of PEM fuel cell after 550h for FC2. First, a full scale equivalent circuit model (ECM) with 10 parameters is developed to describe the electrochemical physics of PEMFC more realistically. The model reduction is suggested because of limited data. Since some parameters remain nearly unchanged due to irrelevance to degradation, it is reasonable to use the degenerated 4-parameter ECM while fixing the other parameters at their means. Despite the model reduction, the degradation pattern is clearly observed through the degenerated 4-parameter ECM. Then the coefficients of the four parameters are estimated by building linear regression models between the parameters and voltage. Since the voltage change after 550h is not provided for FC2, the voltage degradation model is developed by modeling both reversible and irreversible degradation processes. This research also proposes a hybrid prognostic approach to the SOH (or EIS spectra) prediction. The voltage degradation model and the degenerated 4-parameter ECM are first developed based on the observation of the physical phenomenon. They are then trained for the purpose of the SOH prediction with the training EIS data sets (FC1 and FC2). It is demonstrated that this hybrid SOH prediction offers highly accurate prediction of the SOH (or EIS spectra) at t = 666, 830, and 1016h. Moreover, possible error sources are also discussed to further improve the prediction accuracy in future.
Second Chance: A Hybrid Approach for Dynamic Result Caching and Prefetching in Search Engines

Web search engines are known to cache the results of previously issued queries. The stored results typically contain the document summaries and some data that is used to construct the final search result page returned to the user. An alternative strategy is to store in the cache only the result document IDs, which take much less space, allowing results of more queries to be cached. These two strategies lead to an interesting trade-off between the hit rate and the average query response latency. In this work, in order to exploit this trade-off, we propose a hybrid result caching strategy where a dynamic result cache is split into two sections: an HTML cache and a docID cache. Moreover, using a realistic cost model, we evaluate the performance of different result prefetching strategies for the proposed hybrid cache and the baseline HTML-only cache. Finally, we propose a machine learning approach to predict singleton queries, which occur only once in the query stream. We show that when the proposed hybrid result caching strategy is coupled with the singleton query predictor, the hit rate is further improved.
The Role of β-1,4-Galactosyltransferase-I in the Skin Wound-healing Process

Cell-surface carbohydrate chains are known to contribute to cell migration, interaction, and proliferation. β-1,4-galactosyltransferase-I (β-1,4-GalT-I), which is one of the best-studied glycosyltransferases, plays a key role in the synthesis of type 2 chains in N-glycans and the core 2 branch in O-glycans. Recently, it has been reported that skin wound healing is significantly delayed in β-1,4-GalT-I−/− mice. However, the expression of β-1,4-GalT-I and its biological function in the skin wound-healing process remain to be elucidated. We used real-time polymerase chain reaction to demonstrate that the expression of β-1,4-GalT-I mRNA reached plateau values at 12 hours after skin was injured and remained elevated until 11 days after the injury. Furthermore, lectin blotting showed that β-1,4-galactosylated carbohydrate chains were also increased after skin injury. A double-staining method combining lectin-fluorescent staining with RCA-I and immunofluorescence was first used to determine the cellular localization of β-1,4-galactosylated carbohydrate chains. Morphological analysis showed that the chains were primarily expressed in neutrophils and partially expressed in macrophages, endothelial cells, and collagen. Our results suggest that β-1,4-GalT-I and β-1,4-galactosylated carbohydrate chains participate in leukocyte recruitment, angiogenesis, and collagen deposition in the skin wound-healing process.
Efficient Compression and Querying of XML Repositories

With the rapidly increasing popularity of XML as a data format, there is a large demand for efficient techniques in storing and querying XML documents. However XML is by nature verbose, due to repeatedly used tags that describe data. For this reason the storage requirements of XML can be excessive and lead to increased costs for data manipulation. Therefore, it seems natural to use compression techniques to increase the efficiency of storing and querying XML data. In this paper, we propose a new approach called SCQX for Storing, Compressing and Querying XML documents. This approach compresses the structure of an XML document based on exploiting repetitive consecutive tags in the structure, and then SCQX stores the compressed XML structure and the data separately in a robust storage structure that includes a set of access support structures to guarantee fast query performance. Moreover, SCQX supports querying of the compressed XML structure directly and efficiently without requiring decompression. An experimental evaluation on sets of XML data shows the effectiveness of our approach.
Constructing a new Human Rights lexicon: Convention on the Rights of Persons with Disabilities

The Article examines the Convention on the Rights of Persons with Disabilities, which is the first human rights instrument of the millennium to understand how the disability rights discourse has been altered, and to contribute to human rights jurisprudence. This is because the Convention alters the lexicon of disability rights and offers fresh insight on the way to resolve some perennial human rights dilemmas.
Application of targeted proteomics to metabolically engineered Escherichia coli

As synthetic biology matures to compete with chemical transformation of commodity and high‐value compounds, a wide variety of well‐characterized biological parts are needed to facilitate system design. Protein quantification based on selected‐reaction monitoring (SRM) mass spectrometry compliments metabolite and transcript analysis for system characterization and optimizing flux through engineered pathways. By using SRM quantification, we assayed red fluorescent protein (RFP) expressed from plasmids containing several inducible and constitutive promoters and subsequently assessed protein production from the same promoters driving expression of eight mevalonate pathway proteins in Escherichia coli. For each of the promoter systems, the protein level for the first gene in the operon followed that of RFP, however, the levels of proteins produced from genes farther from the promoter were much less consistent. Second, we used targeted proteomics to characterize tyrosine biosynthesis pathway proteins after removal of native regulation. The changes were not expected to cause significant impact on protein levels, yet significant variation in protein abundance was observed and tyrosine production for these strains spanned a range from less than 1 mg/L to greater than 250 mg/L. Overall, our results underscore the importance of targeted proteomics for determining accurate protein levels in engineered systems and fine‐tuning metabolic pathways.
Super-Resolving Multiresolution Images With Band-Independent Geometry of Multispectral Pixels

A new resolution enhancement method is presented for multispectral and multiresolution images, such as those provided by the Sentinel-2 satellites. Starting from the highest resolution bands, band-dependent information (reflectance) is separated from information that is common to all bands (geometry of scene elements). This model is then applied to unmix low-resolution bands, preserving their reflectance, while propagating band-independent information to preserve the subpixel details. A reference implementation is provided, with an application example for super-resolving Sentinel-2 data.
From a Lost-Cause City to a Model City: Determinants of the Policy of Drug Addiction and Abuse Control in the City of Split (1994-2007)

U clanku se analiziraju kljucne odrednice javne politike suzbijanja ovisnosti o drogi i zlouporabe droge Grada Splita od 1994. do 2007. godine. U njemu su prezentirani osnovni rezultati istraživanja koje je provedeno metodom studije slucaja, u sklopu kojega su uporabljeni polustrukturirani intervju, analiza razlicitih dokumenata i drugi metodski postupci. Interpretacija rezultata istraživanja, zasnovana na razlicitim teorijskim pristupima, pokazuje kako je javna politika suzbijanja ovisnosti o drogi i zlouporabe droge Grada Splita rijedak primjer moderne, kvalitetno osmisljene i uspjesne javne politike u suvremenoj Hrvatskoj. Provedba te javne politike, uz ostale cimbenike, znatno je utjecala na zaustavljanje trenda sirenja ovisnosti o heroinu u drugom najvecem gradu u Hrvatskoj krajem prosloga desetljeca i na osjetno smanjenje broja novoregistriranih ovisnika o heroinu u analiziranom razdoblju u cijelosti. Slijedom tih promjena Split je od “ grada slucaja’ ’ u strucnoj i siroj javnosti postao prepoznatljiv kao “ grad model’ ’ suzbijanja ovisnosti o drogi i zlouporabe droge.
Porter's (1980) Generic Strategies and Performance: An Empirical Examination with American Data

Porter's (1980) three generic strategies have received a great deal of attention recently in the literature on strategic management. In this, the first of two papers, we employ methods of taxonomy on the PIMS data base of consumer durable business units to determine whether Porter's differentiation, cost leadership and focus types occur with any degree of regularity. Then, in a sequel paper to appear in O.S. we examine whether the types differ among each other and between types not displaying differentiation or cost leadership in their growth and ROI performance.
Joint source and relay energy-efficient resource allocation for two-hop MIMO-AF systems

This paper proposes a low-complexity joint source and relay energy-efficient resource allocation scheme for the two-hop multiple-input-multiple-output (MIMO) amplify-and-forward (AF) system when channel state information is available. We first simplify the multivariate unconstrained energy efficiency (EE)-based problem and derive a convex closed-form approximation of its objective function as well as closed-form expressions of subchannel rates in both the unconstrained and power constraint cases. We then rely on these expressions for designing a low-complexity energy-efficient joint resource allocation algorithm. Our approach has been compared with a generic nonlinear constrained optimization solver and results have indicated the low-complexity and accuracy of our approach. As an application, we have also compared our EE-based approach against the optimal spectral efficiency (SE)-based joint resource allocation approach and results have shown that our EE-based approach provides a good trade-off between power consumption and SE.
Estimation of Isolation Times of the Island Species in the Drosophila simulans Complex from Multilocus DNA Sequence Data

Background The Drosophila simulans species complex continues to serve as an important model system for the study of new species formation. The complex is comprised of the cosmopolitan species, D. simulans, and two island endemics, D. mauritiana and D. sechellia. A substantial amount of effort has gone into reconstructing the natural history of the complex, in part to infer the context in which functional divergence among the species has arisen. In this regard, a key parameter to be estimated is the initial isolation time (t) of each island species. Loci in regions of low recombination have lower divergence within the complex than do other loci, yet divergence from D. melanogaster is similar for both classes. This might reflect gene flow of the low-recombination loci subsequent to initial isolation, but it might also reflect differential effects of changing population size on the two recombination classes of loci when the low-recombination loci are subject to genetic hitchhiking or pseudohitchhiking Methodology/Principal Findings New DNA sequence variation data for 17 loci corroborate the prior observation from 13 loci that DNA sequence divergence is reduced in genes of low recombination. Two models are presented to estimate t and other relevant parameters (substitution rate correction factors in lineages leading to the island species and, in the case of the 4-parameter model, the ratio of ancestral to extant effective population size) from the multilocus DNA sequence data. Conclusions/Significance In general, it appears that both island species were isolated at about the same time, here estimated at ∼250,000 years ago. It also appears that the difference in divergence patterns of genes in regions of low and higher recombination can be reconciled by allowing a modestly larger effective population size for the ancestral population than for extant D. simulans.
Categorizing 'Intention to Use' E-Government Services through Mobile Phone: The Importance of Front Loading Activities

E-government has often been heralded as the new way forwards for emerging countries. While many such countries are already offering e-government services and are gearing up for further growth, little is actually known of the forming stages that are necessary to ensure a greater rate of success and avoid the traditional failure traps linked to new technology and information system adoption and diffusion. We situate our research in the case of mobile phone as a reflection of the current market situation in emerging countries. We contend, in this paper, that more research is needed to understand future intention to use e-government services through mobile phone technology. Front loading activities both from a government and technology perspectives are required to facilitate the decision making process by users.
Breaking the Excitation-Inhibition Balance Makes the Cortical Network's Space-Time Dynamics Distinguish Simple Visual Scenes

Brain dynamics are often taken to be temporal dynamics of spiking and membrane potentials in a balanced network. Almost all evidence for a balanced network comes from recordings of cell bodies of few single neurons, neglecting more than 99% of the cortical network. We examined the space-time dynamics of excitation and inhibition simultaneously in dendrites and axons over four visual areas of ferrets exposed to visual scenes with stationary and moving objects. The visual stimuli broke the tight balance between excitation and inhibition such that the network exhibited longer episodes of net excitation subsequently balanced by net inhibition, in contrast to a balanced network. Locally in all four areas the amount of net inhibition matched the amount of net excitation with a delay of 125 ms. The space-time dynamics of excitation-inhibition evolved to reduce the complexity of neuron interactions over the whole network to a flow on a low-(3)-dimensional manifold within 80 ms. In contrast to the pure temporal dynamics, the low dimensional flow evolved to distinguish the simple visual scenes.
The Association Between Regular Symptom Monitoring and Self-care Management in Patients With Heart Failure

Background:Symptom monitoring is considered the first step toward self-care management (actions to manage altered symptom status) to avert worsening heart failure (HF). However, empirical evidence demonstrating that symptom monitoring leads to adequate self-care management is lacking. We examined the relationship of adherence to regular symptom monitoring with adequate self-care management in HF patients. Methods and Results:A total of 311 HF patients (60 years, 35% women) were divided into 3 groups by adherence to 2 symptom monitoring behaviors (monitoring daily weights and lower extremity edema). Patients who were adherent to both symptom monitoring behaviors formed the adherent group (15.1%). Those adherent to either of the symptom monitoring behaviors formed the partially adherent group (28.9%). Those adherent to neither of the symptom monitoring behaviors formed the nonadherent group (56.0%). The adjusted odds of performing adequate self-care management were increased by 225% (95% confidence interval, 1.13–4.48) and 344% (95% confidence interval, 1.55–7.62) for the partially adherent and adherent symptom monitoring groups, respectively, compared with the nonadherent group. Conclusion:Adequacy of self-care management was predicted by adherence to symptom monitoring behaviors. This finding suggests that regular symptom monitoring facilitates performance of adequate self-care management, which may contribute to a decrease in preventable hospitalizations in HF.