Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of the Pharmacokinetics of Atorvastatin, Cerivastatin, and Indomethacin Using Kinetic Models Applied to Isolated Rat Hepatocytes

The disposition of atorvastatin, cerivastatin, and indomethacin, established substrates of rat hepatic basolateral uptake transporters, has been evaluated in suspended rat hepatocytes. Cell and media concentration-time data were simultaneously fitted to a model incorporating active uptake, permeation, binding, and metabolism. Use of the model to estimate the ratio of intracellular to extracellular steady-state free drug concentrations demonstrated the strong influence of active uptake on the kinetics of atorvastatin (18:1) and cerivastatin (8:1), in comparison with indomethacin (3.5:1). Indomethacin, however, was shown to have a higher uptake clearance (599 ± 101 μl/min/106 cells) than atorvastatin (375 ± 45 μl/min/106 cells) and cerivastatin (413 ± 47 μl/min/106 cells). The high passive permeability of indomethacin (237 ± 63 μl/min/106 cells) clearly negated the effect of the active transport on the overall disposition. An analogous physiological model was constructed that allowed prediction of the in vivo pharmacokinetics, including the free intracellular concentration in liver. Hepatic clearance was well predicted by the model, in contrast to predictions based on standard methods. Volume of distribution was well predicted for indomethacin and predicted reasonably for atorvastatin and cerivastatin and higher than might be expected for an acid compound. Furthermore, the terminal half-life predictions for all three compounds were within 2-fold of the observed values. The ability to estimate the free-intracellular hepatic concentration of uptake substrates has major benefits in terms of predicting pharmacokinetics, potential CYP-mediated drug-drug interactions, and efficacy of hepatically targeted therapeutics.
Comparative determinations of the /spl chi//sup (2)/ spatial distribution induced in thermally poled silica planar samples

We herein report the comparison of two independent reconstructions of the distribution of the /spl chi//sup (2)/ nonlinear susceptibility induced by thermal poling in planar silica samples. Both nonlinear profiles are quantitatively in good agreement in terms of /spl chi//sup (2)/ magnitude and nonlinear thickness; and qualitatively in agreement in terms of shape. We conclude that both characterization methods used are efficient for the determination of the /spl chi//sup (2)/ susceptibility spatial distribution in bulk samples.
Consensus in the presence of partial synchrony (Preliminary Version)

An apparatus for and a method of moving stripe domains in a direction transverse their length is disclosed. The apparatus includes a layer of magnetizable material in which stripe domains are capable of being generated, sustained and moved. Formed upon the magnetizable layer are two parallel contiguous disk files, each of which is formed of a plurality of linearly aligned similar contiguous Bicore disks. Each Bicore disk is comprised of a disk of a relatively soft magnetizable material, e.g., Permalloy, and a superposed disk of a relatively hard magnetizable material, e.g., Cobalt, sandwiching an insulative layer, e.g., silicon dioxide, SiO2, therebetween. The magnetizations of the superposed soft and hard magnetizable disks of each of the Bicore disks are in a closed, antiparallel aligned direction with the magnetization of each of the soft magnetizable disks of the first contiguous disk file directed across the separating stripe domain propagation area and aligned with but oppositely polarized with respect to the magnetization in the associated soft magnetizable disks in the other, second contiguous disk file. A stripe domain is transferred into the propagation device by coupling the two ends thereof to the two corresponding, oppositely polarized aligned first Bicore disks of the two contiguous disk files. An appropriate propagate drive field, which is directed along the direction of propagation of the stripe domain and which is aligned with the two parallel contiguous disk files, rotates only the magnetizations of the soft magnetizable disks in each of the two contiguous disk files, in a like direction, e.g., the soft magnetizable disks in the first contiguous disk file are rotated in a clockwise direction while the magnetizations of the soft magnetizable disks in the second contiguous disk file are rotated in the counterclockwise direction. The rotating magnetization of the soft magnetizable disks of the two Bicore disks, one at each of the two ends of the stripe domain, carries the stripe domain in the direction of the propagate drive field. When the propagate drive field is suddenly terminated, the magnetizations of the soft magnetizable disks snap back under the influence of the magnetization of the hard magnetizable disk while the stripe domain remains in its new, propagated position downstream between contiguous Bicore disks. Upon successive applications of the propagate drive fields, each end of the stripe domain is transferred from an upstream Bicore disk to the next adjacent downstream Bicore disk while all stripe domains in the propagation device are transferred, in parallel, along the two aligned contiguous disk files through the stripe domain propagation area.
Signature nevi: individuals with multiple melanocytic nevi commonly have similar clinical and histologic patterns

Individuals with multiple melanocytic nevi oftentimes have melanocytic nevi, usually two, with similar clinical and histopathologic patterns that may be typical or atypical. The melanocytic nevi are known in common parlance as signature nevi [1, 2]. In addition to being aware of these nevi, finding multiple unconventional melanocytic nevi with architectural pattern asymmetric and/or cellular pattern atypical helps to lend credence to the diagnosis of melanocytic nevus rather than melanoma. In order to evaluate the concept of the signature nevus we reviewed the histopathologic patterns of melanocytic nevi from patients having at least two nevi with similar histologic patterns.
Benign Cementoblastoma of Primary Mandibular Molars : A Rarity

Benign cementoblastomas are developmental odontogenic tumors that arise from ectomesenchyme of dental follicle and represent about 0.69% to 8% of all odontogenic tumors. The Benign cementoblastomas more frequently affects young males in an age range of 20-30 years, occurring in the mandible about 3 times more than in the maxilla, and it is always physically attached to the tooth roots. Cementoblastomas associated with primary teeth are extremely rare lesions, but must always be considered in the differential diagnosis of hard masses in jaws in children to avoid overdiagnosis. Though locally aggressive, the recurrence is found to be rare if it is completely excised and thoroughly curetted. An intraosseous painful swelling was noted upon intraoral examination of an 8 years old boy. The swelling was of 4months duration and slow growing in nature. OPG revealed a radiopaque mass with radiolucent periphery of roots of mandibular right deciduous molars. Differential diagnosis of odontoma, cementoblastoma and osteoma were made. The clinical, radiographic and histopathological features of the excised specimen led to the diagnosis of cementoblastoma. To our knowledge only 9 cases of cementoblastoma associated with primary teeth were reported in literature. Herewith, we are reporting a rare case report of benign cementoblastoma of deciduous mandibular molars.
Evaluating the Use of Brazilian Companies' Financial Footnotes Texts for Debt Variation Prediction

This article presents a study using Brazilian publicly listed companies' financial statements footnotes, in order to verify if these documents can provide information to predict variations in the debt of the corresponding firms. From a text mining perspective, we built classification models by assigning a class to each company in a period of time based on the variation of the debt to equity ratio. We conducted experiments using two different classifiers: random forest and support vector machine. The caret package in R language was used for this work. When we employed the random forest classifier, we got accuracies 4 percent points greater than the baseline accuracy, suggesting that the textual content of financial statements has some potential use for debt prediction.
Emulating temporal receptive fields of auditory mid-brain neurons for automatic speech recognition

This paper proposes modifications to the Multi-resolution RASTA (MRASTA) feature extraction technique for the automatic speech recognition (ASR). By emulating asymmetries of the temporal receptive field (TRF) profiles of auditory mid-brain neurons, we obtain more than 13% relative improvement in word error rate on OGI-Digits database. Experiments on TIMIT database confirm that proposed modifications are indeed useful.
Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology.

ESC Committee for Practice Guidelines (CPG), Silvia G. Priori (Chairperson) (Italy), Jean-Jacques Blanc (France), Andrzej Budaj (Poland), John Camm (UK), Veronica Dean (France), Jaap Deckers (The Netherlands), Kenneth Dickstein (Norway), John Lekakis (Greece), Keith McGregor (France), Marco Metra (Italy), Joao Morais (Portugal), Ady Osterspey (Germany), Juan Tamargo (Spain), Jose Luis Zamorano (Spain) Document Reviewers, Marco Metra (CPG Review Coordinator) (Italy), Michael Bohm (Germany), Alain Cohen-Solal (France), Martin Cowie (UK), Ulf Dahlstrom (Sweden), Kenneth Dickstein (Norway), Gerasimos S. Filippatos (Greece), Edoardo Gronda (Italy), Richard Hobbs (UK), John K. Kjekshus (Norway), John McMurray (UK), Lars Ryden (Sweden), Gianfranco Sinagra (Italy), Juan Tamargo (Spain), Michal Tendera (Poland), Dirk van Veldhuisen (The Netherlands), Faiez Zannad (France) Guidelines and Expert Consensus Documents aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic procedure. They should be helpful in everyday clinical decision-making. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) and by different organizations and other related societies. This profusion can put at stake the authority and validity of guidelines, which can only be guaranteed if they have been developed by an unquestionable decision-making process. This is one of the reasons why the ESC and others have issued recommendations for formulating and issuing Guidelines and Expert Consensus Documents. In spite of the fact that standards for issuing good quality Guidelines and Expert Consensus Documents are well defined, recent surveys of Guidelines and Expert Consensus Documents published in peer-reviewed journals between 1985 and 1998 have shown that methodological standards were not complied with in the vast majority of cases. It is therefore of great importance that guidelines and recommendations are presented in formats that are …
Machine Translation Evaluation: A Survey

This paper introduces the state-of-the-art machine translation (MT) evaluation survey that contains both manual and automatic evaluation methods. The traditional human evaluation criteria mainly include the intelligibility, fidelity, fluency, adequacy, comprehension, and informativeness. The advanced human assessments include task-oriented measures, post-editing, segment ranking, and extended criteriea, etc. We classify the automatic evaluation methods into two categories, including lexical similarity scenario and linguistic features application. The lexical similarity methods contain edit distance, precision, recall, F-measure, and word order. The linguistic features can be divided into syntactic features and semantic features respectively. The syntactic features include part of speech tag, phrase types and sentence structures, and the semantic features include named entity, synonyms, textual entailment, paraphrase, semantic roles, and language models. Subsequently, we also introduce the evaluation methods for MT evaluation including different correlation scores, and the recent quality estimation (QE) tasks for MT. This paper differs from the existing works \cite{GALEprogram2009,EuroMatrixProject2007} from several aspects, by introducing some recent development of MT evaluation measures, the different classifications from manual to automatic evaluation measures, the introduction of recent QE tasks of MT, and the concise construction of the content.
Expert advice ensemble for thyroid disease diagnosis

Thyroid gland influences the metabolic processes of human body due to the fact that it produces hormones. Hyperthyroidism in caused due to increase in the production of thyroid hormones. In this paper a methodology using an online ensemble of decision trees to detect thyroid-related diseases is proposed. The aim of this work is to improve the diagnostic accuracy of thyroid disease. Initially, feature rejection method is applied to discard 10 irrelevant and redundant features from 29 features. Then, it's shown that the offline ensemble of decision trees provides higher performance than state-of-the-art methodologies. Afterwards, the exponential weights based online ensemble method is implemented which reaches comparable clas­sification performance with offline methodology. The proposed system consists of three stages: feature rejection, training decision trees with different cost schemes and the online classification stage where each classifier is weighted using an exponential weight based algorithm. The performance of online algorithm increases as the number of samples increases, because it contin­uously updates the weights to improve accuracy. The achieved classification accuracy proves the robustness and effectiveness of online version of proposed system in thyroid disease diagnosis.
An atelocollagen honeycomb-shaped scaffold with a membrane seal (ACHMS-scaffold) for the culture of annulus fibrosus cells from an intervertebral disc.

The aim of this study was to investigate the possibility of using the atelocollagen honeycomb-shaped scaffold with a membrane seal (ACHMS-scaffold) for the culture of annulus fibrosus (AF) cells in tissue engineering procedures of intervertebral disc repair. AF cells from the intervertebral discs of Japanese white rabbits were cultured for up to 3 weeks in the ACHMS-scaffold to allow a high density, three-dimensional culture. Although the DNA content in the scaffold increased at a lower rate than in the monolayer culture, scanning electron microscopy data showed that the scaffold was filled with the grown AF cells and produced extracellular matrix on day 21. The amount of type II collagen and its mRNA expression by the scaffold cultured cells were determined using Western blotting and Northern blotting analyses, respectively, and remained at a higher level than in the monolayer cultured cells. Furthermore, glycosaminoglycan (GAG) accumulation in the scaffold culture was at a higher level than in the monolayer culture. Western blot analysis for extracted proteoglycans from the scaffold culture also exhibited a much higher proteoglycan accumulation than the monolayer culture. These results indicate that the AF cells are able to grow and remain phenotypically stable in the scaffold.
Structure of the transition state for the binding of c-Myb and KIX highlights an unexpected order for a disordered system

Significance A considerable fraction of proteins, although functional, does not display a well-ordered native state, posing the structure–function dogma into question. Although different models have been described, the role of protein disorder is still shrouded in mystery. Here, we investigate the mechanism of recognition between an intrinsically unstructured protein and its partner. Unexpectedly, we found the binding to occur with a very high degree of geometrical precision, suggesting that a potential value of disorder is not, in this case, to be searched in the speeding up of the reaction thanks to an increased capture radius. Given that in the cell disordered polypeptides may be more vulnerable than folded domains, the advantage in being natively unfolded remains a conundrum. A classical dogma of molecular biology dictates that the 3D structure of a protein is necessary for its function. However, a considerable fraction of the human proteome, although functional, does not adopt a defined folded state under physiological conditions. These intrinsically disordered proteins tend to fold upon binding to their partners with a molecular mechanism that is elusive to experimental characterization. Indeed, although many hypotheses have been put forward, the functional role (if any) of disorder in these intrinsically denatured systems is still shrouded in mystery. Here, we characterize the structure of the transition state of the binding-induced folding in the reaction between the KIX domain of the CREB-binding protein and the transactivation domain of c-Myb. The analysis, based on the characterization of a series of conservative site-directed mutants, reveals a very high content of native-like structure in the transition state and indicates that the recognition between KIX and c-Myb is geometrically precise. The implications of our results in the light of previous work on intrinsically unstructured systems are discussed.
Ultra-wide-band low noise amplifier using inductive feedback in 90-nm CMOS technology

This paper proposes an inductive feedback technique implemented in the ultra-wide-band (UWB) low noise amplifier (LNA). Using the technique, the proposed circuit not only enhances the bandwidth but also reduces the noise figure. Furthermore, both wide-band matching and small chip area are achieved by adopting only one on-chip inductor in feedback path of the circuit. This UWB LNA was fabricated by using foundry 90 nm CMOS technology. The LNA consumes 30 mW, and occupies 0.375 mm area. Moreover, the measured power gain is 10 dB, 3-dB bandwidth is 14GHz, input third order intercept point (IIP3) is large than −4 dBm, and the noise figure is 5.8 dB during the wideband operation.
Supplement to: Systematic interpretation of microarray data using experiment annotations

Analysis-interfering artifacts (yeast data). The Eurofan II Node B2 project [1, 2, 3, 4, 5, 6, 7] was an enterprise to study the S. cerevisiae transcriptome under various experimental conditions (such as high and low glucose concentrations, calcium shortage or heat shock) on a consistent platform. The investigated dataset comprises 229 out of 253 hybridizations performed by five European groups using whole-genome nylon membrane macroarrays and radioactive label. All experiments were performed using the same type of array, suggesting that they should all be comparable. However, combining all the data in one analysis and ranking the experiment annotations by their variance, we obtain Table 1. It shows which of the numerous parameters correlate to transcription in this experimental context. Unfortunately, the total variance is dominated by the array production batch (‘array series’). We generally observed this artifact to distort otherwise revealing radioactive data [8]. The variance introduced by the different array batches interferes with comparing the yeast hybridizations in a larger context. Because array batch is in the first place, we do not present any other aspect of these data in this paper.
Regulation of Rac1 activation by the low density lipoprotein receptor–related protein

The low density lipoprotein receptor–related protein (LRP-1) binds and mediates the endocytosis of multiple ligands, transports the urokinase-type plasminogen activator receptor (uPAR) and other membrane proteins into endosomes, and binds intracellular adaptor proteins involved in cell signaling. In this paper, we show that in murine embryonic fibroblasts (MEFs) and L929 cells, LRP-1 functions as a major regulator of Rac1 activation, and that this activity depends on uPAR. LRP-1–deficient MEFs demonstrated increased Rac1 activation compared with LRP-1–expressing MEFs, and this property was reversed by expressing the VLDL receptor, a member of the same gene family as LRP-1, with overlapping ligand-binding specificity. Neutralizing the activity of LRP-1 with receptor-associated protein (RAP) increased Rac1 activation and cell migration in MEFs and L929 cells. The same parameters were unaffected by RAP in uPAR−/− MEFs, prepared from uPAR gene knockout embryos, and in uPAR-deficient LM-TK− cells. Untreated uPAR+/+ MEFs demonstrated substantially increased Rac1 activation compared with uPAR−/− MEFs. In addition to Rac1, LRP-1 suppressed activation of extracellular signal–regulated kinase (ERK) in MEFs; however, it was Rac1 (and not ERK) that was responsible for the effects of LRP-1 on MEF migration. Thus, LRP-1 regulates two signaling proteins in the same cell (Rac1 and ERK), both of which may impact on cell migration. In uPAR-negative cells, LRP-1 neutralization does not affect Rac1 activation, and other mechanisms by which LRP-1 may regulate cell migration are not unmasked.
Disruption of LTBP-4 function reduces TGF-β activation and enhances BMP-4 signaling in the lung

Disruption of latent TGF-β binding protein (LTBP)–4 expression in the mouse leads to abnormal lung development and colorectal cancer. Lung fibroblasts from these mice produced decreased amounts of active TGF-β, whereas secretion of latent TGF-β was significantly increased. Expression and secretion of TGF-β2 and -β3 increased considerably. These results suggested that TGF-β activation but not secretion would be severely impaired in LTBP-4 −/− fibroblasts. Microarrays revealed increased expression of bone morphogenic protein (BMP)–4 and decreased expression of its inhibitor gremlin. This finding was accompanied by enhanced expression of BMP-4 target genes, inhibitors of differentiation 1 and 2, and increased deposition of fibronectin-rich extracellular matrix. Accordingly, increased expression of BMP-4 and decreased expression of gremlin were observed in mouse lung. Transfection of LTBP-4 rescued the −/− fibroblast phenotype, while LTBP-1 was inefficient. Treatment with active TGF-β1 rescued BMP-4 and gremlin expression to wild-type levels. Our results indicate that the lack of LTBP-4–mediated targeting and activation of TGF-β1 leads to enhanced BMP-4 signaling in mouse lung.
Handling data skew in parallel joins in shared-nothing systems

Parallel processing continues to be important in large data warehouses. The processing requirements continue to expand in multiple dimensions. These include greater volumes, increasing number of concurrent users, more complex queries, and more applications which define complex logical, semantic, and physical data models. Shared nothing parallel database management systems [16] can scale up "horizontally" by adding more nodes. Most parallel algorithms, however, do not take into account data skew. Data skew occurs naturally in many applications. A query processing skewed data not only slows down its response time, but generates hot nodes, which become a bottleneck throttling the overall system performance. Motivated by real business problems, we propose a new join geography called PRPD (Partial Redistribution & Partial Duplication) to improve the performance and scalability of parallel joins in the presence of data skew in a shared-nothing system. Our experimental results show that PRPD significantly speeds up query elapsed time in the presence of data skew. Our experience shows that eliminating system bottlenecks caused by data skew improves the throughput of the whole system which is important in parallel data warehouses that often run high concurrency workloads.