Miracle-dz/UniFAR-FTUs huggingface dataset:
Saturated free fatty acids induce cholangiocyte lipoapoptosis

Recent studies have identified a cholestatic variant of nonalcoholic fatty liver disease (NAFLD) with portal inflammation and ductular reaction. Based on reports of biliary damage, as well as increased circulating free fatty acids (FFAs) in NAFLD, we hypothesized the involvement of cholangiocyte lipoapoptosis as a mechanism of cellular injury. Here, we demonstrate that the saturated FFAs palmitate and stearate induced robust and rapid cell death in cholangiocytes. Palmitate and stearate induced cholangiocyte lipoapoptosis in a concentration‐dependent manner in multiple cholangiocyte‐derived cell lines. The mechanism of lipoapoptosis relied on the activation of caspase 3/7 activity. There was also a significant up‐regulation of the proapoptotic BH3‐containing protein, PUMA. In addition, palmitate‐induced cholangiocyte lipoapoptosis involved a time‐dependent increase in the nuclear localization of forkhead family of transcription factor 3 (FoxO3). We show evidence for posttranslational modification of FoxO3, including early (6 hours) deacetylation and dephosphorylation that coincide with localization of FoxO3 in the nuclear compartment. By 16 hours, nuclear FoxO3 is both phosphorylated and acetylated. Knockdown studies confirmed that FoxO3 and its downstream target, PUMA, were critical for palmitate‐ and stearate‐induced cholangiocyte lipoapoptosis. Interestingly, cultured cholangiocyte‐derived cells did not accumulate appreciable amounts of neutral lipid upon FFA treatment. Conclusion: Our data show that the saturated FFAs palmitate and stearate induced cholangiocyte lipoapoptosis by way of caspase activation, nuclear translocation of FoxO3, and increased proapoptotic PUMA expression. These results suggest that cholangiocyte injury may occur through lipoapoptosis in NAFLD and nonalcoholic steatohepatitis patients. (Hepatology 2014;60:1941–1955)
Relevance of Situational Context in Studying Learning as Changing Participation

Seemingly small situational problems with understanding and changes in the environment can constitute critical aspects in learning a task. I will describe and discuss through a detailed analysis of correction practices in interaction how learning in a situation influences a learner's ability to distinguish and handle continuity and change in related situations. Correction is “an understanding‐display device” by which participants in interaction can check and correct problems occurring in activity. The socio‐cultural understanding of learning as changing participation is the point of departure. The data material consists of longitudinal video recordings from naturally occurring physiotherapist‐patient encounters focussing the interplay between talk, gaze, gesture, body orientation, and artefacts. Through an integrated interactional exploration of smaller alternating cycles of changes from other to self regarding who is responsible for detecting and solving problems, the findings show how a learner's capability to notice similarities and differences develops in progressive situations. The analysis contributes empirically to expanding the understanding of some generative aspects of learning related to the issue of transfer in educational science.
Spontaneous Affect Recognition from Audio-visual Cues using Multi-resolution Analysis

It is essential for computer to get affective state of the user for better HumanComputer Interaction. The audio-visual signals play a major role to know the change of human behaviour or affective state of the human being. This paper presents a framework for spontaneous affect recognition from audio-visual cues. To predict spontaneous emotion, the spectral and prosodic features from audio signal and visual features from video signal are extracted followed by Fisher Discriminant Analysis (FDA) in order to select most discriminative features. The multiresolution analysis (MRA) of audio-visual signals is performed using the Discrete Wavelet Transform, a classical transform for analysis of one/two dimensional signals. The spectral and prosodic features from audio signal are also extracted using Mel Frequency Cepstral Coefficient (MFCC). The experiments were performed on eNTERFACE and RML database. The performance of the proposed system was measured in terms of precision, recall and f-measures. Multilayer Perceptron (MLP) and Support Vector Machine (SVM) classifiers are deployed to classify six categories (Anger, Disgust, Fear, Happiness, Sadness and Surprise) of basic emotion. The experimental results prove that our system shows significant performance with 80.5% and above accuracy with fusion of audio-visual cues.
The cognitive, affective and physiological impact of infant crying: a comparison of two laboratory methodologies

Objective: The present study investigated two experimental paradigms to explore whether individual differences in adult responses to crying were related to the method of presentation of the crying infant – namely, a video simulation or a life-like programmable doll. Background: The importance of understanding individual differences in caregiver responses to infant crying is well recognised, but assessment of caregiver responses presents considerable methodological challenges. Method: Participants were 106 female childless undergraduate students. Responses assessed included self-report measures of self-efficacy beliefs, feelings of empathy toward the crying infant, caregiver concern and irritation, and heart-rate reactivity. Participants were randomly allocated to exposure to either a life-like crying doll or to a video of a crying infant. Results: Compared to those in the video condition, participants exposed to the crying doll showed lower self-efficacy beliefs, experienced greater feelings of irritation and a greater change in heart-rate responses, p < . 05, but no differences in feelings of concern or empathy towards the infant. Conclusion: Findings provide preliminary evidence that the crying doll paradigm may be a more ecologically valid approach to exploring the impact of crying on adults; however, methodological considerations related to individual differences in physiological responses need further clarification in future research.
An Optimal Allocation Model for Large Complex Water Resources System Considering Water supply and Ecological Needs

Water resources are very important to support the socio-economic development and maintain environmental health, which is a typical issue in water resources management. In this study, we developed an optimal allocation model for a large complex system of water resources by considering both water supply and river ecological benefits. The water supply benefit is defined as the minimum water deficit for different water users, while the ecological benefit involves making the reservoir release as close as possible to the natural streamflow. To solve this problem, the combination of decomposition-coordination (DC) and discrete differential dynamic programming (DDDP) methods were proposed. The proposed methods first decomposed a large system with multi-objective programming into subsystems, and the optimal solution of each subsystem was accomplished by the DDDP method to solve the system efficiently. Then the subsystems’ solutions were coordinated to figure out the near global optimal solution. The proposed models were tested in the Lingui and Yongfu County, Guilin City in China. Results show that the optimal reservoir release is close to the natural flow regime and there is a slight water deficit ratio in both level years. The water supply objective is more sensitive to the system model compared with the ecological objective, and the result of water allocation is optimized when the reservoir release is as close as possible to the natural flow based on the minimum water deficit. The proposed system model could facilitate sustainable water use and provide technical support for water resources management in economic development.
The large extent of dark matter haloes probed by the formation of tidal dwarf galaxies

In several interacting systems, gas accumulations as massive as 10 9 $M_{\odot}$ are observed near the tip of tidal tails, and are thought to be possible progenitors of Tidal Dwarf Galaxies. Using N -body simulations of galaxy interactions, we show that the existence of such features requires that dark matter haloes around spiral galaxies extend at least ten times further than the stellar disks. The massive gas clouds formed in our simulations have a kinematical origin and gravitationally collapse into dwarf galaxies that often survive for a few billion years.
A fixedpoint approach to (co)inductive and (co)datatype definitions

This paper presents a xedpoint approach to inductive denitions. Instead of using a syntactic test such as \strictly positive," the approach lets denitions involve any operators that have been proved monotone. It is conceptually simple, which has allowed the easy implementation of mutual recursion and iterated denitions. It also handles coinductive denitions: simply replace the least xedpoint by a greatest xedpoint.
Pairwised Specific Distance Learning from Physical Linkages

In real tasks, usually a good classification performance can only be obtained when a good distance metric is obtained; therefore, distance metric learning has attracted significant attention in the past few years. Typical studies of distance metric learning evaluate how to construct an appropriate distance metric that is able to separate training data points from different classes or satisfy a set of constraints (e.g., must-links and/or cannot-links). It is noteworthy that this task becomes challenging when there are only limited labeled training data points and no constraints are given explicitly. Moreover, most existing approaches aim to construct a global distance metric that is applicable to all data points. However, different data points may have different properties and may require different distance metrics. We notice that data points in real tasks are often connected by physical links (e.g., people are linked with each other in social networks; personal webpages are often connected to other webpages, including nonpersonal webpages), but the linkage information has not been exploited in distance metric learning. In this article, we develop a pairwised specific distance (PSD) approach that exploits the structures of physical linkages and in particular captures the key observations that nonmetric and clique linkages imply the appearance of different or unique semantics, respectively. It is noteworthy that, rather than generating a global distance, PSD generates different distances for different pairs of data points; this property is desired in applications involving complicated data semantics. We mainly present PSD for multi-class learning and further extend it to multi-label learning. Experimental results validate the effectiveness of PSD, especially in the scenarios in which there are very limited labeled training data points and no explicit constraints are given.
Characterization of the Naturally Occurring Oxacillinase of Acinetobacter baumannii

ABSTRACT A chromosomally encoded oxacillinase, OXA-69, was characterized from Acinetobacter baumannii AYE. β-Lactamase OXA-69 shared 97% amino acid identity with the recently described OXA-51 enzyme of A. baumannii and 62 and 56% amino acid identity with the carbapenem-hydrolyzing oxacillinases OXA-24 and OXA-23, respectively. Biochemical characterization of the purified OXA-69 revealed a narrow-spectrum hydrolysis profile but including, at a low level, imipenem and meropenem. By PCR and sequencing blaOXA-69-like genes were identified in all A. baumannii strains tested (n = 12), suggesting that this oxacillinase is naturally occurring in that species.
A Black Woman's Journey Into a Predominately White Academic World

The paucity of Black women at predominately White institutions of higher education is well recognized. Like me, some Black women survived the gauntlet of coursework, qualifying examinations, and dissertation research and writing in pursuit of doctoral degrees, followed by the whirlwind campus visits that are integral to the faculty recruitment process. Upon our arrival, we were confronted by the challenges of being African American and female in a majority White university community. This article is a personal journey that spans 40 years of my life—from an 18-year-old freshman to a tenure-track assistant professor—at the same university.
N-Best Tokenization in a GMM-SVM Language Identification System

N-best or lattice-based tokenization has been widely used in speech-related classification tasks. In this paper, we extended the n-best tokenization approach to GMM-based language identification systems with either maximum likelihood (ML) trained or SVM-based language models. We explored the effect of n-best tokenization in training or testing, and its interaction with n-gram order and system fusion. We showed that for both systems, the n-best tokenization gives good performance improvement. However, the SVM-based system benefited from both n-best training and test while the ML-trained system can only benefit from n-best training. Results show n-best tokenization can reduce the relative EER of our best GMM-SVM system by about 5% for 30s and 10s tests.
Object and Action Classification with Latent Variables

In this paper we propose a generic framework to incorporate unobserved auxiliary information for classifying objects and actions. This framework allows us to explicitly account for localisation and alignment of representations for generic object and action classes as latent variables. We approach this problem in the discriminative setting as learning a max-margin classifier that infers the class label along with the latent variables. Through this paper we make the following contributions a) We provide a method for incorporating latent variables into object and action classification b) We specifically account for the presence of an explicit class related subregion which can include foreground and/or background. c) We explore a way to learn a better classifier by iterative expansion of the latent parameter space. We demonstrate the performance of our approach by rigorous experimental evaluation on a number of standard object and action recognition datasets.
Phenotypic definition of Chiari type I malformation coupled with high‐density SNP genome screen shows significant evidence for linkage to regions on chromosomes 9 and 15

Chiari type I malformation (CMI; OMIM 118420) is narrowly defined when the tonsils of the cerebellum extend below the foramen magnum, leading to a variety of neurological symptoms. It is widely thought that a small posterior fossa (PF) volume, relative to the total cranial volume leads to a cramped cerebellum and herniation of the tonsils into the top of the spinal column. In a collection of magnetic resonance imagings (MRIs) from affected individuals and their family members, we measured correlations between ten cranial morphologies and estimated their heritability in these families. Correlations between bones delineating the PF and significant heritability of PF volume (0.955, P = 0.003) support the cramped PF theory and a genetic basis for this condition. In a collection of 23 families with 71 affected individuals, we performed a genome wide linkage screen of over 10,000 SNPs across the genome to identify regions of linkage to CMI. Two‐point LOD scores on chromosome 15 reached 3.3 and multipoint scores in this region identified a 13 cM region with LOD scores over 1 (15q21.1‐22.3). This region contains a biologically plausible gene for CMI, fibrillin‐1, which is a major gene in Marfan syndrome and has been linked to Shprintzen–Goldberg syndrome, of which CMI is a distinguishing characteristic. Multipoint LOD scores on chromosome 9 maximized at 3.05, identifying a 40 cM region with LOD scores over 1 (9q21.33‐33.1) and a tighter region with multipoint LOD scores over 2 that was only 8.5 cM. This linkage evidence supports a genetic role in Chiari malformation and justifies further exploration with fine mapping and investigation of candidate genes in these regions. © 2006 Wiley‐Liss, Inc.
Sphere formation and self-renewal capacity of melanoma cells is affected by the microenvironment

Melanomas contain subsets of cancer stem-like cells with tumor-initiating capacity. The frequency of these cells in the tumor is still a topic of debate. We investigated the phenotypic plasticity of cancer cells grown as melanospheres to elucidate the influence of the microenvironment on some features of melanoma stem-like cells. Cells from surgical specimens of nodular melanoma were grown as anchorage-independent melanospheres in a stem cell medium and as adherent monolayer cultures in the presence of serum. Proliferation and viability were measured by cell counting and an acid phosphatase assay; surface marker expression was evaluated by flow cytometry, and the clonogenic potential of single cells was assessed by growth in soft agar. Patient-derived melanoma cells could be maintained in cell culture for more than 16 months when grown as melanospheres. In the presence of serum, melanospheres completely changed their growth characteristics and formed adherent monolayers. The transition from melanospheres to monolayers was accompanied by an apparent loss of clonogenic potential, an increased proliferation rate, and altered expressions of cell surface markers ABCB5, CD133, and CD49f. These changes, however, were reversible. Compared with adherent monolayer cultures, melanospheres are enriched in cells with clonogenic potential, reflecting the self-renewing capacity of cancer stem-like cells. This clonogenic potential can be lost and regained depending on the growth conditions. Our results demonstrate how easily melanoma cells change their function upon exposure to external stimuli and suggest that the frequency of melanoma stem-like cells strongly depends on the microenvironment.
Evaluating the Intention to Use Technology among Student Teachers: A Structural Equation Modeling Approach

This study examined student teachers’ self-reported intentions to use technology. One hundred and fifty-nine participants completed a survey questionnaire measuring their responses to four constructs derived from the Technology Acceptance Model (TAM). Using Structural Equation Modeling (SEM), a path analysis was conducted to analyze the data. The results of this study showed that the TAM is a valid model in explaining student teachers’ intention to use technology. Overall, this study indicated that attitude towards computer use had the largest effect on the intention to use technology, followed by perceived usefulness and perceived ease of use.
Three Dimensional Saliency Calculation Using Splatting

Using perception in the context of rendering is a wide spread field. It can be used to speed up calculations or create more detailed images by refining important areas. Saliency, as a perception based method, can identify regions of interest, which should contain more detail. But currently no complete mapping of the 2D operators to an 3D equivalent has been defined. We propose a Bidirectional Saliency Weight Distribution Function (in short BSWDF). Using this function to evaluate a surface element the local saliency value can be obtained. The global value can be retrieved by using a splatting algorithm, which combines the individual features based on the distance of the object. As most objects do not change during rendering, e.g. by deformation, a preprocess can create a lookup cache for these values.
Flow by a Ring of Negative Charges in the Outer Pore of BK Ca Channels. Part II: Neutralization of Aspartate 292 Reduces Long Channel Openings and Gating Current Slow Component

Neutralization of the aspartate near the selectivity ﬁlter in the GYG D pore sequence (D292N) of the voltage- and Ca 2 (cid:1) -activated K (cid:1) channel (MaxiK, BKCa) does not prevent conduction like the corresponding mutation in Shaker channel, but profoundly affects major biophysical properties of the channel (Haug, T., D. Sigg, S. Ciani, L. Toro, E. Stefani, and R. Olcese. 2004. J . Gen . Physiol . 124:173–184). Upon depolarizations, the D292N mutant elicited mostly gating current, followed by small or no ionic current, at voltages where the wild-type hSlo channel displayed robust ionic current. In fact, while the voltage dependence of the gating current was not signiﬁcantly affected by the mutation, the overall activation curve was shifted by (cid:1) 20 mV toward more depolarized potentials. Several lines of evidence suggest that the mutation prevents population of certain open states that in the wild type lead to high open probability. The activation curves of WT and D292N can both be ﬁtted to the sum of two Boltzmann distributions with identical slope factors and half activation potentials, just by changing their relative amplitudes. The steeper and more negative component of the activation curve was drastically reduced by the D292N mutation (from 0.65 to 0.30), suggesting that the population of open states that occurs early in the activation pathway is reduced. Furthermore, the slow component of the gating current, which has been suggested to reﬂect transitions from closed to open states, was greatly reduced in D292N channels. The D292N mutation also affected the limiting open probability: at 0 mV, the limiting open probability dropped from (cid:1) 0.5 for the wild-type channel to 0.06 in D292N (in 1 mM [Ca 2 (cid:1) ] i ). In addition to these effects on gating charge and open probability, as already described in Part I, the D292N mutation introduces a (cid:1) 40% reduction of outward single channel conductance, as well as a strong outward rectiﬁcation.
Tumor Cell Plasticity and Angiogenesis in Human Melanomas

Recent molecular studies provide evidence for a significant transcriptional plasticity of tumor cell subpopulations that facilitate an active contribution to tumor vasculature. This feature is accompanied by morphological changes both in vitro and in vivo. Herein, we investigated the morphological plasticity of tumor cells with special focus on vasculogenic mimicry and neovascularisation in human melanoma and mouse xenografts of human melanoma cell lines. In melanoma xenograft experiments, different vessel markers and green fluorescent protein expression were used to show how melanoma cells contribute to neovascularization. Additionally, we analyzed neovascularization in 49 primary melanomas and 175 melanoma metastases using immunostaining for blood (CD34) and lymphatic (D2–40) vessel-specific markers. We found significantly more lymphatic vessels in primary melanomas than in melanoma metastases (p<0.0001). In contrast to the near absence of lymphatic vessels within metastases, we found extensive blood micro-neovascularization. Blood micro-neovascularization was absent in micro metastases (less than 2 mm). A significant inverse correlation between Glut-1 expression (implying local hypoxia) and the presence of microvessels indicates their functional activity as blood vessels (p<0.0001). We suggest that the hypoxic microenvironment in metastases contributes to a phenotype switch allowing melanoma cells to physically contribute to blood vessel formation.