Miracle-dz/UniFAR-FTUs huggingface dataset:
Capitalizing on the Autophagic Response for Treatment of Liver Disease Caused by Alpha-1-Antitrypsin Deficiency and Other Genetic Diseases

Alpha-1-antitrypsin deficiency (ATD) is one of the most common genetic causes of liver disease and is a prototype of liver diseases caused by the pathologic accumulation of aggregated mutant alpha-1-antitrypsin Z (ATZ) within liver cells. In the case of ATD-associated liver disease, the resulting “gain-of-function” toxicity can lead to serious clinical manifestations, including cirrhosis and hepatocellular carcinoma. Currently, the only definitive therapy for ATD-associated liver disease is liver transplantation, but recent efforts have demonstrated the exciting potential for novel therapies that target disposal of the mutant protein aggregates by harnessing a cellular homeostasis mechanism called autophagy. In this review, we will summarize research advances on autophagy and genetic liver diseases. We will discuss autophagy enhancer strategies for liver disease due to ATD and another genetic liver disease, inherited hypofibrinogenemia, caused by the proteotoxic effects of a misfolded protein. On the basis of recent evidence that autophagy plays a role in cellular lipid degradation, we also speculate about autophagy enhancer strategies for treatment of hepatic lipid storage diseases such as cholesterol ester storage disease.
Conjugacy in Garside groups II: structure of the ultra summit set

This paper is the second in a series in which the authors study the conjugacy decision problem (CDP) and the conjugacy search problem (CSP) in Garside groups. The ultra summit set USS.X/ of an element X in a Garside group G is a finite set of elements in G, which is a complete invariant of the conjugacy class of X in G. A fundamental question, if one wishes to find bounds on the size of USS.X/, is to understand its structure. In this paper we introduce two new operations on elements Y 2 USS.X/, called 'partial cycling' and 'partial twisted decycling', and prove that if Y; Z 2 USS.X/, then Y and Z are related by sequences of partial cyclings and partial twisted decyclings. These operations are a concrete way to understand the minimal simple elements whose existence follows from the convexity property of ultra summit sets. Using partial cycling and partial twisted decycling, we investigate the structure of a directed graphX determined by USS.X/, and show thatX can be decomposed into 'black' and 'grey' subgraphs. There are applications relating to the authors' program for finding a polynomial solution to the CDP/CSP in the case of braids, which is outlined in the first paper of this series. A different application is to give a new algorithm for solving the CDP/CSP in Garside groups which is faster than all other known algorithms, even though its theoretical complexity is the same as that of the established algorithm using ultra summit sets. There are also applications to the theory of reductive groups.
The Influence of Sustained Selective Attention on Stimulus Selectivity in Macaque Visual Area MT

Remarkable alterations of perception during long-lasting attentional processes have been described in several recent studies. Although these findings have gained much interest, almost nothing is known about the modulation of neuronal responses during sustained attention. Therefore, we investigated the effect of prolonged selective attention on neuronal feature selectivity. Awake macaque monkeys were trained to perform a motion-tracking task that required attending one of two simultaneously presented moving bars for up to 15 sec. Extracellular recordings were obtained from neurons in macaque motion-sensitive middle temporal visual area (MT/V5). Under conditions of attention, we found high and constant direction selectivity over time. This was expressed by a strong and persistent response contrast between presentations of preferred and nonpreferred stimuli in successive motion cycles. With attention directed to another moving bar, neuronal responses to the behaviorally irrelevant stimulus became continuously less specific for the direction of motion. In particular, increasingly higher firing rates for motion in null direction caused a strong reduction of direction selectivity, which further increased with enhanced proximity between target and distracter bar. A passive condition experiment revealed that this reduction occurred only when motion remained the behaviorally relevant feature but disappeared when attention was withdrawn from this feature domain. Thus, sustained attention seems to stabilize direction selectivity of neurons in area MT against a time and competition-dependent degradation, whereas nonattended objects suffer from a reduced neuronal representation.
Lung function and symptoms among indigenous Mayan women exposed to high levels of indoor air pollution.

SETTING Indoor air pollution from burning of biomass fuel in open fires is a known risk factor for chronic obstructive pulmonary disease (COPD) in developing countries. OBJECTIVE To estimate the prevalence of respiratory symptoms and lung function among women in rural Guatemala and to describe the methods and practical issues associated with the assessment of respiratory health. DESIGN Information about respiratory symptoms, lung function and individual measurement of exposure was collected cross-sectionally among 350 Mayan-Indian women aged 15-50 years who used traditional open fires. RESULTS These women, exposed to indoor air pollution since birth, had a relatively high prevalence of cough (22.6%), phlegm (15.1%), wheeze (25.1%) and tightness in the chest (31.4%). Respiratory symptoms were positively associated with exposure levels. Lung function was higher than the most feasible reference population (average above predicted forced expiratory volume in 1 s [FEV(1)] +4.5% and forced vital capacity [FVC] +4.2%). Only one woman had a FEV(1)/FVC ratio lower than 70%. CONCLUSIONS According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, almost one third of these young non-smoking women were at risk (stage 0) of developing COPD. The methodological issues encountered during the study highlight the importance of standardising approaches to local adaptation of established questionnaires to study respiratory health in rural areas of developing countries.
Range image registration using hierarchical segmentation and clustering

An accurate, robust, and automatic registration of overlapping range images is usually a pre-requisite step for range image analysis and applications. While accurate depiction of object geometry requires the increase of the resolutions of images and thus, the amount of data to process, an efficient processing of such data then usually becomes an issue. In this paper, we first employ the efficient tensor analysis and k means clustering methods to hierarchically segment and cluster the original range images into a small number of planar patches represented as the closest points in the original images to their centroids. Then an advanced ICP variant is adopted to register such closest points. Finally, another ICP variant is used to refine the registration results obtained over all the points in the images. The experimental results based on real range images show that the proposed technique significantly outperforms the selected two state of the art ones for accurate and efficient registration of overlapping range images.
Language dominance, preference and awareness: a case study of two multilingual children in a bilingual community

This case study of two multilingual boys (aged 6-7) has two aims. Firstly, it explores how the participants view their language proficiency, language dominance and language preference and investigates how their statements show evidence of metalinguistic awareness. Naturalistic data, semi-structured interviews and background questionnaires were used to collect comprehensive data. The second aim is to compare participants' statements about their own language proficiency and dominance with data from an oral narrative task in order to investigate whether they accurately predicted their dominant language. The participants performed the task in three languages (English, Spanish and Catalan) and their fluency and lexical richness was analyzed. Overall, fluency measures matched with their perceptions. However, lexical richness results (as measured by Guiraud's Index and lexical density) were inconclusive. In summation, the participants demonstrate that young multilingual children are capable of providing accurate information on their language proficiency from very early on. The dissertation ends with directions for future research. LANGUAGE DOMINANCE, PREFERENCE AND AWARENESS: A CASE STUDY 3
A Primal-Dual Accelerated Interior Point Method Whose Running Time Depends Only on A

We propose a primal-dual \layered-step" interior point (LIP) algorithm for linear programming with data given by real numbers. This algorithm follows the central path, either with short steps or with a new type of step called a \layered least squares" (LLS) step. The algorithm returns an exact optimum after a nite number of steps|in particular, after O(n 3:5 c(A)) iterations, where c(A) is a function of This paper represents a simpliication of an earlier manuscript \An accelerated interior point method whose running depends only on A" by the same authors.
Contention-sensing and dynamic spectrum co-use in secondary user Cognitive Radio societies

Emerging standards in Cognitive Radio seek to alleviate the problem of spectrum scarcity by leveraging spectrum under-utilization through dynamic spectrum access (DSA). Unlicensed users (“secondary”) may opportunistically make use of channels during times when the licensed (“primary”) user is absent. The “open access” paradigm proposed by FCC mandates the study of primary-secondary dynamics, as well as secondary-secondary dynamics to better understand the implications of uncoordinated competition for limited number of resources between secondary users. In this paper, we consider long term etiquette between secondary users engaged in spectrum co-use. In order to maximize throughput, by avoiding over-crowded channels, we propose a novel approach wherein secondary users have the ability to “sense” very approximate contention levels at a single spectrum band at each point in time. System performance under the contention-sensing paradigm is compared to two schemes: first, a previously defined non-cooperative game model; second, a new model which allows for spectrum foraging, but without providing secondary users the ability to sense contention in a band. Through simulation experiments, we show that the contention-sensing paradigm results in significantly better co-use of spectrum resources. Additionally, our experiments demonstrate that the proposed contention-sensing paradigm continues to outperform when the ratio of secondary users to spectrum bands is increased. Thus, the new schemes described here may be of critical importance in a future where we expect the number of secondary users to grow exponentially and thus require a scalable mechanism for opportunistic scavenging of unused spectrum.
The Mechanical Environment Modulates Intracellular Calcium Oscillation Activities of Myofibroblasts

Myofibroblast contraction is fundamental in the excessive tissue remodeling that is characteristic of fibrotic tissue contractures. Tissue remodeling during development of fibrosis leads to gradually increasing stiffness of the extracellular matrix. We propose that this increased stiffness positively feeds back on the contractile activities of myofibroblasts. We have previously shown that cycles of contraction directly correlate with periodic intracellular calcium oscillations in cultured myofibroblasts. We analyze cytosolic calcium dynamics using fluorescent calcium indicators to evaluate the possible impact of mechanical stress on myofibroblast contractile activity. To modulate extracellular mechanics, we seeded primary rat subcutaneous myofibroblasts on silicone substrates and into collagen gels of different elastic modulus. We modulated cell stress by cell growth on differently adhesive culture substrates, by restricting cell spreading area on micro-printed adhesive islands, and depolymerizing actin with Cytochalasin D. In general, calcium oscillation frequencies in myofibroblasts increased with increasing mechanical challenge. These results provide new insight on how changing mechanical conditions for myofibroblasts are encoded in calcium oscillations and possibly explain how reparative cells adapt their contractile behavior to the stresses occurring in normal and pathological tissue repair.
Metastability and small eigenvalues in Markov chains

In this Letter we announce rigorous results that elucidate the relation between metastable states and low-lying eigenvalues in Markov chains in a much more general setting and with considerably greater precision than has so far been available. This includes a sharp uncertainty principle relating all low-lying eigenvalues to mean times of metastable transitions, a relation between the support of eigenfunctions and the attractor of a metastable state and sharp estimates of the convergence of the probability distribution of the metastable transition times to the exponential distribution.
Pupillary behavior in positive and negative emotions

Emotion recognition process is proven to be an essential tool to increase human-computer reaction, interpret social relations, investigate mental health, and study human behavior. Pupil diameter (PD) has been addressed as the most reliable approach to identify emotions. This is because it is controlled by Automatic Nervous System (ANS) and is easy to detect. The goal of this paper is to identify the difference in PD due to individual's positive and negative emotional states. The paper introduces experimental results obtained using eye-tracking system with 30 participants. Initial results obtained by applying differently paired-sample t-test suggested a significant increase in pupil dilation during negative emotions compared to positive ones. It also shows steeper, higher, more sustained and longer dilation in high arousal negative stimuli.
Sound production and spectral hearing sensitivity in the Hawaiian sergeant damselfish, Abudefduf abdominalis

SUMMARY Sounds provide important signals for inter- and intraspecific communication in fishes, but few studies examine fish acoustic behavior in the context of coevolution of sound production and hearing ability within a species. This study characterizes the acoustic behavior in a reproductive population of the Hawaiian sergeant fish, Abudefduf abdominalis, and compares acoustic features to hearing ability, measured by the auditory evoked potential (AEP) technique. Sergeant fish produce sounds at close distances to the intended receiver (⩽1–2 body lengths), with different pulse characteristics that are associated primarily with aggression, nest preparation and courtship–female-visit behaviors. Energy peaks of all sounds were between 90 and 380 Hz, whereas courtship–visit sounds had a pulse repetition rate of 125 Hz with harmonic intervals up to 1 kHz. AEP threshold, which is probably higher than the behavioral threshold, indicates best sensitivity at low frequencies (95–240 Hz), with the lowest threshold at 125 Hz (123–127 dBrms re: 1 μPa). Thus, sound production and hearing in A. abdominalis are closely matched in the frequency domain and are useful for courtship and mating at close distances. Measured hearing thresholds did not differ among males and females during spawning or non-spawning periods, which indicates a lack of sex differences and seasonal variation in hearing capabilities. These data provide the first evidence that Abudefduf uses true acoustic communication on a level similar to that of both more derived (e.g. Dascyllus, Chromis) and more basal (e.g. Stegastes) soniferous pomacentrids. This correlation between sound production and hearing ability is consistent with the sensory drive model of signal evolution in which the sender and receiver systems coevolve within the constraints of the environment to maximize information transfer of acoustic signals.
Algorithm 888: Spherical Harmonic Transform Algorithms

A collection of MATLAB classes for computing and using spherical harmonic transforms is presented. Methods of these classes compute differential operators on the sphere and are used to solve simple partial differential equations in a spherical geometry. The spectral synthesis and analysis algorithms using fast Fourier transforms and Legendre transforms with the associated Legendre functions are presented in detail. A set of methods associated with a spectral_field class provides spectral approximation to the differential operators ∇ ⋯, ∇ ×, ∇, and ∇2 in spherical geometry. Laplace inversion and Helmholtz equation solvers are also methods for this class. The use of the class and methods in MATLAB is demonstrated by the solution of the barotropic vorticity equation on the sphere. A survey of alternative algorithms is given and implementations for parallel high performance computers are discussed in the context of global climate and weather models.
A let-7 microRNA-Binding Site Polymorphism in KRAS Predicts Improved Outcome in Patients with Metastatic Colorectal Cancer Treated with Salvage Cetuximab/Panitumumab Monotherapy

Purpose: An inherited mutation in KRAS (LCS6-variant or rs61764370) results in altered control of the KRAS oncogene. We studied this biomarker's correlation to anti-EGFR monoclonal antibody (mAb) therapy response in patients with metastatic colorectal cancer. Experimental Design: LCS6-variant and KRAS/BRAF mutational status was determined in 512 patients with metastatic colorectal cancer treated with salvage anti-EGFR mAb therapy, and findings correlated with outcome. Reporters were tested in colon cancer cell lines to evaluate the differential response of the LCS6-variant allele to therapy exposure. Results: In this study, 21.2% (109 of 512) of patients with metastatic colorectal cancer had the LCS6-variant (TG/GG), which was found twice as frequently in the BRAF-mutated versus the wild-type (WT) group (P = 0.03). LCS6-variant patients had significantly longer progression- free survival (PFS) with anti-EGFR mAb monotherapy treatment in the whole cohort (16.85 vs. 7.85 weeks; P = 0.019) and in the double WT (KRAS and BRAF) patient population (18 vs. 10.4 weeks; P = 0.039). Combination therapy (mAbs plus chemotherapy) led to improved PFS and overall survival (OS) for nonvariant patients, and brought their outcome to levels comparable with LCS6-variant patients receiving anti-EGFR mAb monotherapy. Combination therapy did not lead to improved PFS or OS for LCS6-variant patients. Cell line studies confirmed a unique response of the LCS6-variant allele to both anti-EGFR mAb monotherapy and chemotherapy. Conclusions: LCS6-variant patients with metastatic colorectal cancer have an excellent response to anti-EGFR mAb monotherapy, without any benefit from the addition of chemotherapy. These findings further confirm the importance of this mutation as a biomarker of anti-EGFR mAb response in patients with metastatic colorectal cancer, and warrant further prospective confirmation. Clin Cancer Res; 20(17); 4499–510. ©2014 AACR.
Comparison of Trypan Blue Dye Exclusion and Fluorometric Assays for Mammalian Cell Viability Determinations

A hemocytometer‐based trypan blue dye exclusion cell quantitation and viability assay was compared with a similar assay using simultaneous fluorometric staining with fluorescein diacetate and propidium iodide. Viable and nonviable cell densities were measured, and culture viability was calculated both during the normal growth cycle of a murine hybridoma and in response to the application of millimolar concentrations of either tert‐butyl hydroperoxide or ferrous iron. During the early phase of rapid hybridoma cell growth, assay‐based differences in viable cell density were not significant. As the culture aged, the trypan blue dye exclusion assay significantly overestimated cell viability, thereby underestimating nonviable cell density and yielding an erroneous estimation of the overall viability of the culture. Because of its lack of ambiguity in the identification of stained, nonviable cells and its resulting increased accuracy in the estimation of culture viability, the fluorometric assay was considered a better choice for the evaluation of cell viability.
Coproduction of speech and emotions: visual and acoustic modifications of some phonetic labial targets#

This paper concerns the bimodal transmission of emotive speech and describes how the expression of joy, surprise, sadness, disgust, anger, and fear, leads to visual and acoustic target modifications in some Italian phonemes. Current knowledge on the audio-visual transmission of emotive speech traditionally concerns global prosodic and intonational characteristics of speech and facial configurations. In this research we intend to integrate this approach with the analysis of the interaction between labial configurations, peculiar to each emotion, and the articulatory lip movements defined by phonetic-phonological rules, specific to the vowels and consonants /’a/, /b/, /v/ ([1], [2]). Moreover, we present the correlations between articulatory data and the spectral features of the co-produced acoustic signal .
Significance of changes in endurance shuttle walking performance

Background The endurance shuttle walking test (ESWT) has shown good responsiveness to interventions in patients with chronic obstructive pulmonary disease (COPD). However, the minimal important difference (MID) for this test remains unknown, therefore limiting its interpretability. Methods Patients with COPD who completed two or more ESWTs following pulmonary rehabilitation (n=132; forced expiratory volume in 1 s (FEV1) 48±22%) or bronchodilation (n=69; FEV1 50±12%) rated their performance of the day in comparison with their previous performance on a 7-point scale ranging from −3 (large deterioration) to +3 (large improvement). The relationship between subjective perception of changes and objective changes in performance during the shuttle walk was evaluated. Results Following pulmonary rehabilitation, the anchor-based approach did not allow a valid estimation of the MID in the ESWT performance to be obtained. After bronchodilation, patient ratings of change correlated significantly with the difference in walking distance (r=0.53, p<0.001) and endurance time (r=0.55, p<0.001). For the pharmacotherapy data, regression analysis indicated that a 65 s (95% CI 45 to 85) change in endurance time and a 95 m (95% CI 60 to 115) change in walking distance were associated with a 1-point change in the rating of change scale. These changes represented 13–15% of the baseline values. Conclusions A change in endurance shuttle walking performance of 45–85 s (or 60–115 m) after bronchodilation is likely to be perceived by patients. This MID value may be specific to the intervention from which it was derived.