Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolism and clinical pharmacokinetics of 2-methyl-n-(2′-(pyrrolidinyl-1-ylsulfonyl)-n-[1,1′-biphenyl]-4-yl)propran-1-amine: insights into monoamine oxidase- and CYP-mediated disposition by integration of in vitro ADME tools

Abstract 1. In early discovery stages, 2-methyl-N-(2′-(pyrrolidinyl-1-ylsulfonyl)-[1,1′-biphenyl]-4-yl)propan-1-amine (PBPA) demonstrated monoamine oxidase A (MAO-A) and cytochrome P450 (CYP)-mediated clearance. While human liver microsomes predicted low CLb PBPA demonstrated a moderate CLp/F in humans. The plasma pharmacokinetic (PK) of PBPA was characterized by unexpected high inter-individual variability. Hence, a retrospective analysis was undertaken to understand the disposition processes of PBPA, by applying in vitro mechanistic tools. 2. The in vitro-to-in vivo of rat CLb of PBPA was calculated as similar to that of human, suggesting rat to be a better predictor of a MAO-A/CYP substrate, but not dog or monkey; this is consistent with differences in expression of MAO-A in rat, dog, monkey and human. Fraction metabolized (fm) of human MAO A (hMAO-A) (50%), CYP3A4 (8%), CYP3A5 (16%) and CYP2D6 (29%) was determined, in vitro. 3. While the fm of CYP3A5 was <50%, Michaelis–Menten kinetics demonstrated that it was a higher capacity pathway compared with MAO-A, 2D6 and 3A4. This was consistent with strong association of dose-normalized plasma Cmax and area under the plasma concentration time curve (AUC0-tlast) of PBPA with CYP3A5 genotype, but not with genotype of CYP2D6. 4. This investigation demonstrates the value of integrating in vitro mechanistic tools to gain comprehensive understanding of disposition properties of drug candidates, in a discovery paradigm and prior to the investment in clinical trials.
DART: a toolkit for rapid design exploration of augmented reality experiences

In this paper, we describe The Designer's Augmented Reality Toolkit (DART). DART is built on top of Macromedia Director, a widely used multimedia development environment. We summarize the most significant problems faced by designers working with AR in the real world, and discuss how DART addresses them. Most of DART is implemented in an interpreted scripting language, and can be modified by designers to suit their needs. Our work focuses on supporting early design activities, especially a rapid transition from story-boards to working experience, so that the experiential part of a design can be tested early and often. DART allows designers to specify complex relationships between the physical and virtual worlds, and supports 3D animatic actors (informal, sketch-based content) in addition to more polished content. Designers can capture and replay synchronized video and sensor data, allowing them to work off-site and to test specific parts of their experience more effectively.
Nuclear Localization of Diacylglycerol Kinase Alpha in K562 Cells Is Involved in Cell Cycle Progression

Phosphatidylinositol (PI) signaling is an essential regulator of cell motility and proliferation. A portion of PI metabolism and signaling takes place in the nuclear compartment of eukaryotic cells, where an array of kinases and phosphatases localize and modulate PI. Among these, Diacylglycerol Kinases (DGKs) are a class of phosphotransferases that phosphorylate diacylglycerol and induce the synthesis of phosphatidic acid. Nuclear DGKalpha modulates cell cycle progression, and its activity or expression can lead to changes in the phosphorylated status of the Retinoblastoma protein, thus, impairing G1/S transition and, subsequently, inducing cell cycle arrest, which is often uncoupled with apoptosis or autophagy induction. Here we report for the first time not only that the DGKalpha isoform is highly expressed in the nuclei of human erythroleukemia cell line K562, but also that its nuclear activity drives K562 cells through the G1/S transition during cell cycle progression. J. Cell. Physiol. 232: 2550–2557, 2017. © 2016 Wiley Periodicals, Inc.
Opposing roles of PIK3CA gene alterations to EZH2 signaling in non-muscle invasive bladder cancer

The high rates of tumor recurrence and progression represent a major clinical problem in non-muscle invasive bladder cancer. Previous data showed that EZH2-dependent signaling mediates these processes, whereas the frequent alterations of PIK3CA gene (copy gains and mutations) are predictive of reduced recurrence. Here we show, using clinical samples and bladder cancer cell lines, a functional interaction between EZH2- and PIK3CA-dependent signaling pathways. PIK3CA alterations mediated, on the one hand, the increased expression of two miRNAs, miR-101 and miR-138, which posttranscriptionally downregulate EZH2 expression. On the other hand, PIK3CA alterations facilitate the activation of Akt which phosphorylates EZH2 on Ser21, precluding the trimethylation of histone H3 in K27. Remarkably the increased expression of miR101 or miR138 and the expression of Ser21-phosphorylated EZH2 are good prognostic factors regarding non-muscle invasive bladder cancer recurrence and progression. Collectively, this study provides molecular evidences indicating that the gene expression rewiring occurring in primary bladder tumors, associated with increased EZH2 expression and activity and mediating the increased recurrence and progression risk, are prevented by PIK3CA-dependent signaling. This molecular process may have deep implications in the management of bladder cancer patients and in the design of novel molecularly targeted therapeutic approaches.
Sampling and distortion tradeoffs for bandlimited periodic signals

In this paper, the optimal sampling strategies (uniform or nonuniform) and distortion tradeoffs for stationary bandlimited periodic signals are studied. We justify and use both the average and variance of distortion as the performance criteria. To compute the optimal distortion, one needs to find the optimal sampling locations, as well as the optimal pre-sampling filter. A complete characterization of the optimal distortion for the rates lower than half the Landau rate is provided. It is shown that nonuniform sampling outperforms uniform sampling. In addition, this nonuniform sampling is robust with respect to missing samples. Next, for the rates higher than half the Landau rate, we find bounds that are shown to be tight for some special cases. An extension of the results for random discrete periodic signals is discussed, with simulation results indicating that the intuitions from the continuous domain carry over to the discrete domain.
The complex physiology of Cellvibrio japonicus xylan degradation relies on a single cytoplasmic β‐xylosidase for xylo‐oligosaccharide utilization

Lignocellulose degradation by microbes plays a central role in global carbon cycling, human gut metabolism and renewable energy technologies. While considerable effort has been put into understanding the biochemical aspects of lignocellulose degradation, much less work has been done to understand how these enzymes work in an in vivo context. Here, we report a systems level study of xylan degradation in the saprophytic bacterium Cellvibrio japonicus. Transcriptome analysis indicated seven genes that encode carbohydrate active enzymes were up‐regulated during growth with xylan containing media. In‐frame deletion analysis of these genes found that only gly43F is critical for utilization of xylo‐oligosaccharides, xylan, and arabinoxylan. Heterologous expression of gly43F was sufficient for the utilization of xylo‐oligosaccharides in Escherichia coli. Additional analysis found that the xyn11A, xyn11B, abf43L, abf43K, and abf51A gene products were critical for utilization of arabinoxylan. Furthermore, a predicted transporter (CJA_1315) was required for effective utilization of xylan substrates, and we propose this unannotated gene be called xntA (xylan transporter A). Our major findings are (i) C. japonicus employs both secreted and surface associated enzymes for xylan degradation, which differs from the strategy used for cellulose degradation, and (ii) a single cytoplasmic β‐xylosidase is essential for the utilization of xylo‐oligosaccharides.
FiST: Scalable XML Document Filtering by Sequencing Twig Patterns

In recent years, publish-subscribe (pub-sub) systems based on XML document filtering have received much attention. In a typical pub-sub system, subscribed users specify their interest in profiles expressed in the XPath language, and each new content is matched against the user profiles so that the content is delivered to only the interested subscribers. As the number of subscribed users and their profiles can grow very large, the scalability of the system is critical to the success of pub-sub services. In this paper, we propose a novel scalable filtering system called FiST (Filtering by Sequencing Twigs) that transforms twig patterns expressed in XPath and XML documents into sequences using Prufer's method. As a consequence, instead of matching linear paths of twig patterns individually and merging the matches during post-processing, FiST performs holistic matching of twig patterns with incoming documents. FiST organizes the sequences into a dynamic hash based index for efficient filtering. We demonstrate that our holistic matching approach yields lower filtering cost and good scalability under various situations.
Self-learning system with automatic feedback for text answers

This paper presents details about a system developed using Natural Language Processing tools and methodologies to automatically evaluate a text answer by comparing the semantic similarity between the model answer with the provided student answer. System generates a score according to the matching percentage of the semantic similarity using the assigned marking pattern for the question. This system is embedded in a web application to be provided as a service for students and teachers to promote self-learning through question answering.
Novel message dissemination mechanism and mathematical model for safety applications in VANET

With the increase in the population of cities and transport on the road, there is an increase in traffic congestion and accidents. To avoid traffic jam and vehicle's collision on road safety applications are being developed using Vehicular Adhoc Networks (VANETs). This paper deals with the message dissemination protocol, which is in the most need after a crash in a platoon of vehicles to disseminate alert message to avoid multiple collision, roadblock or call emergency services. To circulate the message in the extended area, vehicles equipped with the wireless interface relay this information. The paper proposes a message dissemination mechanism with the intelligence of the need of re-broadcasting without introducing any new control message in the network. It reduces the number of redundant copies and times of re-broadcast. The paper also includes a mathematical model for the expected results.
Surface defects inspection method in hot slab continuous casting process

Based on the laser triangulation and machine vision technology, a three-dimensional quantitative inspection method for continuous cast slab surface defects was established, which adopted one laser and two array charge coupled device cameras and an optimal laser stripe imaging algorithm. In addition, the laser scanning system establishing method is described in detail in this paper. A laser stripe edge shape extraction method on the slab surface is proposed that utilises an improved edge scanning extraction model in accordance with the charge coupled device camera frame frequency. The detection accuracy control algorithm is presented and finally the three-dimensional image reconstruction method for slab surface defect shape was also studied. Based on the research work, the possibility of the presented laser scanning system was verified through industrial application experiments in a steel plant.
Directional Limits on Motion Transparency Assessed Through Colour-Motion Binding

Motion-defined transparency is the perception of two or more distinct moving surfaces at the same retinal location. We explored the limits of motion transparency using superimposed surfaces of randomly positioned dots defined by differences in motion direction and colour. In one experiment, dots were red or green and we varied the proportion of dots of a single colour that moved in a single direction (‘colour-motion coherence’) and measured the threshold direction difference for discriminating between two directions. When colour-motion coherences were high (e.g., 90% of red dots moving in one direction), a smaller direction difference was required to correctly bind colour with direction than at low coherences. In another experiment, we varied the direction difference between the surfaces and measured the threshold colour-motion coherence required to discriminate between them. Generally, colour-motion coherence thresholds decreased with increasing direction differences, stabilising at direction differences around 45°. Different stimulus durations were compared, and thresholds were higher at the shortest (150 ms) compared with the longest (1,000 ms) duration. These results highlight different yet interrelated aspects of the task and the fundamental limits of the mechanisms involved: the resolution of narrowly separated directions in motion processing and the local sampling of dot colours from each surface.
Experimental Study of Cyclic Rolling-Contact Fatigue of Silicon Nitride Balls

A newly developed pure-rolling fatigue test rig with three contact points for bearing balls was used to perform rolling-contact fatigue (RCF) tests. The fatigue properties of GCr 15 steel balls and two kinds of Si 3 N 4 ceramic balls (GSN-200 and NBD-200) produced with different technologies were compared. Life test data, summarized in accordance with the Weibull theory, showed that the life of the GSN-200 balls was close to that of the GCr 15 balls, whereas the life of the NBD-200 balls was much longer than those of GSN-200 and GCr 15 . Under the same working condition, the temperature rise of all the ceramic balls was lower than that of the steel balls. Ball surfaces were examined after failure with optical microscopy and scanning electron microscopy. It was identified by test that the failure mode of ceramic balls was surface spall. The research shows that subsurface cracks play a dominant role in spalling failure. These cracks originated from volume defects of the material and propagate to form elliptical fatigue spalls.
Phenylalanine regulates initiation of digestive enzyme mRNA translation in pancreatic acinar cells and tissue segments in dairy calves

As new nutritional strategies for ruminant are designed to change production efficiency by improving the supply of rumen protect protein, lipid, and even starch, the digestive system must fit to utilize these increased nutrient supplies, especially the pancreas. The objective of this study was to investigate the effects of phenylalanine (Phe) on digestive enzymes synthesis or secretion and cellular signaling in pancreatic acinar (PA) cells of dairy calves. The PA cells isolated from fresh pancreas of dairy calves, and cultured in completed RIPA 1640 medium with no fetal serum but 0, 0.15 and 0.45 mM Phe at 37°C in CO2 incubator for 120 min. The pancreatic tissue segments (PTS) was cut approximately 2 × 2 mm from the fresh pancreas, and incubated in oxygenated Krebs-Ringer bicarbonate (KRB) buffer containing 0 or 0.35 mM Phe at 39°C for 180 min, and the samples were collected every 60 min after incubation. In PA cells, Phe increased (P < 0.05) the α-amylase secretion and mRNA expression, the phosphorylation of ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4EBP1). In PTS, the Phe increased (P < 0.05) α-amylase and trypsin synthesis, secretion and mRNA expression, as well as the phosphorylation of S6K1 and 4EBP1. Conclusively, these results suggested that Phe regulates the synthesis or secretion of α-amylase, trypsin and lipase through mRNA translation initiation factors – S6K1 and 4EBP1.
In-vivo analysis of ankle joint movement for patient-specific kinematic characterization

In this article, a method for the experimental in-vivo characterization of the ankle kinematics is proposed. The method is meant to improve personalization of various ankle joint treatments, such as surgical decision-making or design and application of an orthosis, possibly to increase their effectiveness. This characterization in fact would make the treatments more compatible with the specific patient’s joint physiological conditions. This article describes the experimental procedure and the analytical method adopted, based on the instantaneous and mean helical axis theories. The results obtained in this experimental analysis reveal that more accurate techniques are necessary for a robust in-vivo assessment of the tibio-talar axis of rotation.
Four Steps to Interpreting Arterial Blood Gases

This article examines acid-base balance and the interpretation of arterial blood gases (ABG). The article begins with a brief revision of related physiology, followed by a description of the primary disorders associated with acid-base imbalance. The normal ranges and the significance of abnormal ABG results are explored. The article concludes by providing an easy to follow four-step guide to ABG interpretation with practice examples presented in the CPD task section.
Multistability of a class of biological systems

Multistability of biological systems with complex nonlinear regulatory schemes is an important research topic in system biology. In many models of biological systems, the regulatory functions are of saturation type. The linear sectors, in which the saturation type functions reside, have been extensively adopted to deal with these saturation type functions. The stability analysis resulting from linear sectors is however often conservative as a wide linear section is required to include a large portion of a saturation type function. In this paper, we utilize piecewise linear sectors, recently adopted in nonlinear control theory, to investigate multistability of a class of biological systems with sum regulatory schemes. We will estimate the domain of attraction of each stable equilibrium. A genetic toggle switch in Escherichia coli is employed as an example to illustrate the applicability and effectiveness of our analysis method.
Induction of de novo α-synuclein fibrillization in a neuronal model for Parkinson’s disease

Significance Although it has been established for over 100 years that Lewy bodies (LBs) represent the major pathological hallmark of Parkinson's disease (PD), we still do not know why these fibrillar intraneuronal inclusions of α-synuclein (α-Syn) protein form, or how they contribute to disease progression. One of the major causes underlying this gap in knowledge is the lack of animal models that reproduce the formation of fibrillar LB-like inclusions. In this study, we show that the absence of human α-Syn (hα-Syn) fibrillization into LBs in mice can be attributed to interactions between hα-Syn and its endogenously expressed mouse α-Syn homologue. Moreover, we provide well-characterized primary neuronal and in vivo models that recapitulate the main molecular feature of PD, bona fide α-Syn fibrillization. Lewy bodies (LBs) are intraneuronal inclusions consisting primarily of fibrillized human α-synuclein (hα-Syn) protein, which represent the major pathological hallmark of Parkinson's disease (PD). Although doubling hα-Syn expression provokes LB pathology in humans, hα-Syn overexpression does not trigger the formation of fibrillar LB-like inclusions in mice. We hypothesized that interactions between exogenous hα-Syn and endogenous mouse synuclein homologs could be attenuating hα-Syn fibrillization in mice, and therefore, we systematically assessed hα-Syn aggregation propensity in neurons derived from α-Syn–KO, β-Syn–KO, γ-Syn–KO, and triple-KO mice lacking expression of all three synuclein homologs. Herein, we show that hα-Syn forms hyperphosphorylated (at S129) and ubiquitin-positive LB-like inclusions in primary neurons of α-Syn–KO, β-Syn–KO, and triple-KO mice, as well as in transgenic α-Syn–KO mouse brains in vivo. Importantly, correlative light and electron microscopy, immunogold labeling, and thioflavin-S binding established their fibrillar ultrastructure, and fluorescence recovery after photobleaching/photoconversion experiments showed that these inclusions grow in size and incorporate soluble proteins. We further investigated whether the presence of homologous α-Syn species would interfere with the seeding and spreading of α-Syn pathology. Our results are in line with increasing evidence demonstrating that the spreading of α-Syn pathology is most prominent when the injected preformed fibrils and host-expressed α-Syn monomers are from the same species. These findings provide insights that will help advance the development of neuronal and in vivo models for understanding mechanisms underlying hα-Syn intraneuronal fibrillization and its contribution to PD pathogenesis, and for screening pharmacologic and genetic modulators of α-Syn fibrillization in neurons.
Design and Development of a Framework for an Automatic Answer Evaluation System Based on Similarity Measures

Abstract The assessment of answers is an important process that requires great effort from evaluators. This assessment process requires high concentration without any fluctuations in mood. This substantiates the need to automate answer script evaluation. Regarding text answer evaluation, sentence similarity measures have been widely used to compare student written answers with reference texts. In this paper, we propose an automated answer evaluation system that uses our proposed cosine-based sentence similarity measures to evaluate the answers. Cosine measures have proved to be effective in comparing between free text student answers and reference texts. Here we propose a set of novel cosine-based sentence similarity measures with varied approaches of creating document vector space. In addition to this, we propose a novel synset-based word similarity measure for computation of document vectors coupled with varied approaches for dimensionality-reduction for reducing vector space dimensions. Thus, we propose 21 cosine-based sentence similarity measures and measured their performance using MSR paraphrase corpus and Li’s benchmark datasets. We also use these measures for automatic answer evaluation system and compare their performances using the Kaggle short answer and essay dataset. The performance of the system-generated scores is compared with the human scores using Pearson correlation. The results show that system and human scores have correlation between each other.