Miracle-dz/UniFAR-FTUs huggingface dataset:
Large animal models of atherosclerosis – new tools for persistent problems in cardiovascular medicine

Coronary heart disease and ischaemic stroke caused by atherosclerosis are leading causes of illness and death worldwide. Small animal models have provided insight into the fundamental mechanisms driving early atherosclerosis, but it is increasingly clear that new strategies and research tools are needed to translate these discoveries into improved prevention and treatment of symptomatic atherosclerosis in humans. Key challenges include better understanding of processes in late atherosclerosis, factors affecting atherosclerosis in the coronary bed, and the development of reliable imaging biomarker tools for risk stratification and monitoring of drug effects in humans. Efficient large animal models of atherosclerosis may help tackle these problems. Recent years have seen tremendous advances in gene‐editing tools for large animals. This has made it possible to create gene‐modified minipigs that develop atherosclerosis with many similarities to humans in terms of predilection for lesion sites and histopathology. Together with existing porcine models of atherosclerosis that are based on spontaneous mutations or severe diabetes, such models open new avenues for translational research in atherosclerosis. In this review, we discuss the merits of different animal models of atherosclerosis and give examples of important research problems where porcine models could prove pivotal for progress. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Battered Immigrant Women and the Legal System: A Therapeutic Jurisprudence Perspective*

Battered immigrant women face tremendous barriers to using the U.S. criminal justice system to respond to the violence in their lives. These include various social, economic, cultural, and legal restrictions as well as hardships, which deter immigrant women from seeking relief. For those women who overcome these barriers and do access the system, there are additional problems to solve in order to obtain help. The multifaceted obstacles can create antitherapeutic effects for these women, thereby reducing their current and future use of the system. Using a therapeutic jurisprudence framework, we propose a series of policy recommendations and interaction strategies for working with battered immigrant women in culturally appropriate, empowering ways. The recommendations call for changes to criminal justice system procedures and require collaborative working relationships among legal practitioners, the professionals, and advocates who work with immigrant women and populations. We argue that a therapeutic jurisprudence approach endorsed by all parties involved may enhance battered immigrant women’s willingness to access the justice system, minimize the system’s anti-therapeutic effects, and maximize its therapeutic impact on this vulnerable group.
How Does Stress Lead to Risk of Alcohol Relapse?

Empirical findings from human laboratory and brain-imaging studies are consistent with clinical observations and indicate that chronic alcohol-related dysfunction in emotional and stress responses plays a role in motivation to consume alcohol in people with alcohol use disorders. Recent findings on differences in stress responsivity in alcohol-dependent versus nondependent social drinkers demonstrate alterations in stress pathways that partially may explain the significant contribution of stress-related mechanisms on craving and relapse susceptibility. These findings have significant implications for clinical practice, including (1) the development of novel brain and stress biology–related measures of relapse risk that could serve as biomarkers to identify those most at risk of alcohol relapse during early recovery from alcoholism; and (2) the development of novel interventions that target stress-related effects on the motivation to drink alcohol and on relapse outcomese
Spectroscopic Correlation of Mechanical Properties of PVC/PMMA Polymer Blend

PVC/ PMMA polymer blends are characterized at molecular level by FTIR-ATR spectroscopy providing important insight into the molecular interactions responsible for the enhancement of its mechanical properties. The changes in mechanical properties are reflected by the changes in the FTIR-ATR spectrum. The mechanical properties of such poly blends revealed a substantial increase in Young’s modulus and ultimate tensile strength after initial drop at 10% of PMMA. A comparative study of mechanical properties of PVC/ PMMA polymer blends with different weight percentage are carried out and their results are co-related with FTIR – ATR spectral studies and important conclusions are drawn about the possible molecular interactions between constituent polymers.
THE DIGITAL CLOCKWORK MUSE: A COMPUTATIONAL MODEL OF AESTHETIC EVOLUTION

This paper presents a computational model of creativity that attempts to capture within a social context an important aspect of the art and design process: the search for novelty. The computational model consists of multiple novelty-seeking agents that can assess the interestingness of artworks. The agents can communicate to particularly interesting artworks to others. Agents can also communicate to reward other agents for finding interesting artworks. We present the results from running experiments to investigate the effects of searching for different degrees of novelty on the artworks produced and the social organisation of the agents.
Putting the Brakes on Enactive Perception

Alva Noe's Action in Perception offers a provocative and vigorous defense of the thesis that vision is enactive: visual experience depends on dispositional motor responses. On this view, vision and action are inextricably bound. In this review, I argue against enactive perception. I raise objections to seven lines of evidence that appear in Noe's book, and I indicate some reasons for thinking that vision can operate independently of motor responses. I conclude that the relationship between vision and action is causal, not constitutive. I then address three other contentious hypotheses in the book. Noe argues that visual states are not pictorial; he argues that all perception is conceptual; and he argues that the external world makes a constitutive contribution to experience. I am unpersuaded by these arguments, and I offer reasons to resist Noe's conclusions.
The Role of Erythropoietin and Erythropoiesis-Stimulating Agents in Tumor Progression

Over the past few decades, understanding of the physiologic function of erythropoietin (EPO) has evolved significantly. EPO binds to erythropoietin receptors (EPOR), initiating signaling that stimulates growth, inhibits apoptosis, and induces the differentiation of erythroid progenitors to increase red blood cell mass. EPO has additionally been shown to exert tissue-protective effects on multiple tissues, suggesting a pleiotropic mechanism of action. Erythropoiesis-stimulating agents (ESA) are used clinically for treating cancer-related anemia [chemotherapy-induced anemia (CIA)]. Recent clinical trials have reported increased adverse events and/or reduced survival in ESA-treated cancer patients receiving chemotherapy, potentially related to EPO-induced cancer progression. Signaling pathways downstream of EPO/EPOR have been shown to influence numerous cellular functions in both normal and tumor cells, including proliferation, apoptosis, and drug resistance. Some studies have reported effects on proliferation, reduced chemotherapy efficacy, reduction of apoptosis, and resistance to selective therapies on cancer cell lines, whereas others have shown null effects. In addition, newer targeted cancer therapies that are directed toward specific signaling pathways may be antagonized by ESAs. This molecular interplay between anticancer agents and potential survival signals triggered by ESAs may have been underestimated and may contribute toward decreased survival seen in certain trials. As more targeted anticancer therapies become available, these types of interactions may mitigate therapeutic efficacy by allowing tumor cells to acquire drug resistance. Therefore, a more complete understanding of the complex pathways involved will allow for the rational use of ESAs for the safe treatment of CIA in oncology patients. Clin Cancer Res; 17(20); 6373–80. ©2011 AACR.
Increased beat-to-beat T-wave variability in myocardial infarction patients

Abstract The purpose of this study was to investigate the beat-to-beat variability of T-waves (TWV) and to assess the diagnostic capabilities of T-wave-based features for myocardial infarction (MI). A total of 148 recordings of standard 12-lead electrocardiograms (ECGs) from 79 MI patients (22 females, mean age 63±12 years; 57 males, mean age 57±10 years) and 69 recordings from healthy subjects (HS) (17 females, 42±18 years; 52 males, 40±13 years) were studied. For the quantification of beat-to-beat QT intervals in ECG signal, a template-matching algorithm was applied. To study the T-waves beat-to-beat, we measured the angle between T-wave max and T-wave end with respect to Q-wave (∠α) and T-wave amplitudes. We computed the standard deviation (SD) of beat-to-beat T-wave features and QT intervals as markers of variability in T-waves and QT intervals, respectively, for both patients and HS. Moreover, we investigated the differences in the studied features based on gender and age for both groups. Significantly increased TWV and QT interval variability (QTV) were found in MI patients compared to HS (p<0.05). No significant differences were observed based on gender or age. TWV may have some diagnostic attributes that may facilitate identifying patients with MI. In addition, the proposed beat-to-beat angle variability was found to be independent of heart rate variations. Moreover, the proposed feature seems to have higher sensitivity than previously reported feature (QT interval and T-wave amplitude) variability for identifying patients with MI.
Group sparse representation of adaptive sub-domain selection for image classification

Recent years have seen an increasing interest in codebook-based model(bag-of-words-BOW) for image representation, which includes the basic bag-of-words model and its improved version for local descriptor reconstruction with sparse coding (SC) and locality-constrained linear coding (LLC) etc. Although the recent coding strategies in the BoW model can lead to prospect performance using large amounts of codes (codebooks) for image classification, it is usually computational expensive for obtaining the global image representation through calculating the similarities between each local descriptor and all codes. Therefore, this study proposes to represent a local descriptor with an adaptive code or its variation modes (adaptive subdomain) in a small set of codebooks. The proposed strategy can adaptively select one code to saliently representation, or adaptively select one sub-domain of a code for group sparse reconstruction of a local descriptor. Due to computational cost mainly on the similarity calculation between local descriptors and the predefined codebooks, our proposed strategy using small set of codebook can greatly reduce computational time, and in addition, shows prospect performances for image classification on an scene database, called OM-RON scene dataset, and the benchmark data: 15 natural scene dataset.
Interactions between mutualist Wigglesworthia and tsetse peptidoglycan recognition protein (PGRP-LB) influence trypanosome transmission

Tsetse flies, the sole vectors of African trypanosomes, have coevolved with mutualistic endosymbiont Wigglesworthia glossinidiae. Elimination of Wigglesworthia renders tsetse sterile and increases their trypanosome infection susceptibility. We show that a tsetse peptidoglycan recognition protein (PGRP-LB) is crucial for symbiotic tolerance and trypanosome infection processes. Tsetse pgrp-lb is expressed in the Wigglesworthia-harboring organ (bacteriome) in the midgut, and its level of expression correlates with symbiont numbers. Adult tsetse cured of Wigglesworthia infections have significantly lower pgrp-lb levels than corresponding normal adults. RNA interference (RNAi)-mediated depletion of pgrp-lb results in the activation of the immune deficiency (IMD) signaling pathway and leads to the synthesis of antimicrobial peptides (AMPs), which decrease Wigglesworthia density. Depletion of pgrp-lb also increases the host's susceptibility to trypanosome infections. Finally, parasitized adults have significantly lower pgrp-lb levels than flies, which have successfully eliminated trypanosome infections. When both PGRP-LB and IMD immunity pathway functions are blocked, flies become unusually susceptible to parasitism. Based on the presence of conserved amidase domains, tsetse PGRP-LB may scavenge the peptidoglycan (PGN) released by Wigglesworthia and prevent the activation of symbiont-damaging host immune responses. In addition, tsetse PGRP-LB may have an anti-protozoal activity that confers parasite resistance. The symbiotic adaptations and the limited exposure of tsetse to foreign microbes may have led to the considerable differences in pgrp-lb expression and regulation noted in tsetse from that of closely related Drosophila. A dynamic interplay between Wigglesworthia and host immunity apparently is influential in tsetse's ability to transmit trypanosomes.
Comparison of Fungal Activities on Wood and Leaf Litter in Unaltered and Nutrient-Enriched Headwater Streams

ABSTRACT Fungi are the dominant organisms decomposing leaf litter in streams and mediating energy transfer to other trophic levels. However, less is known about their role in decomposing submerged wood. This study provides the first estimates of fungal production on wood and compares the importance of fungi in the decomposition of submerged wood versus that of leaves at the ecosystem scale. We determined fungal biomass (ergosterol) and activity associated with randomly collected small wood (<40 mm diameter) and leaves in two southern Appalachian streams (reference and nutrient enriched) over an annual cycle. Fungal production (from rates of radiolabeled acetate incorporation into ergosterol) and microbial respiration on wood (per gram of detrital C) were about an order of magnitude lower than those on leaves. Microbial activity (per gram of C) was significantly higher in the nutrient-enriched stream. Despite a standing crop of wood two to three times higher than that of leaves in both streams, fungal production on an areal basis was lower on wood than on leaves (4.3 and 15.8 g C m−2 year−1 in the reference stream; 5.5 and 33.1 g C m−2 year−1 in the enriched stream). However, since the annual input of wood was five times lower than that of leaves, the proportion of organic matter input directly assimilated by fungi was comparable for these substrates (15.4 [wood] and 11.3% [leaves] in the reference stream; 20.0 [wood] and 20.2% [leaves] in the enriched stream). Despite a significantly lower fungal activity on wood than on leaves (per gram of detrital C), fungi can be equally important in processing both leaves and wood in streams.
The Breast Cancer β4 Integrin and Endothelial Human CLCA2 Mediate Lung Metastasis*

Adhesion of blood-borne cancer cells to the endothelium is a critical determinant of organ-specific metastasis. Here we show that colonization of the lungs by human breast cancer cells is correlated with cell surface expression of the α6β4 integrin and adhesion to human CLCA2 (hCLCA2), a Ca2+-sensitive chloride channel protein that is expressed on the endothelial cell luminal surface of pulmonary arteries, arterioles, and venules. Tumor cell adhesion to endothelial hCLCA2 is mediated by the β4 integrin, establishing for the first time a cell-cell adhesion property for this integrin that involves an entirely new adhesion partner. This adhesion is augmented by an increased surface expression of the α6β4 integrin in breast cancer cells selected in vivo for enhanced lung colonization but abolished by the specific cleavage of the β4 integrin with matrilysin. β4 integrin/hCLCA2 adhesion-blocking antibodies directed against either of the two interacting adhesion molecules inhibit lung colonization, while overexpression of the β4 integrin in a model murine tumor cell line of modest lung colonization potential significantly increases the lung metastatic performance. Our data clearly show that the β4/hCLCA2 adhesion is critical for lung metastasis, yet expression of the β4 integrin in many benign breast tumors shows that this integrin is insufficient to bestow metastatic competence on cells that lack invasiveness and other established properties of metastatic cells.
Vitamin D-Directed Rheostatic Regulation of Monocyte Antibacterial Responses1

The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) enhances innate immunity by inducing the cathelicidin antimicrobial peptide (hCAP). In monocytes/macrophages, this occurs primarily in response to activation of TLR, that induce expression of the vitamin D receptor and localized synthesis of 1,25(OH)2D from precursor 25-hydroxyvitamin D3 (25OHD). To clarify the relationship between vitamin D and innate immunity, we assessed changes in hCAP expression in vivo and ex vivo in human subjects attending a bone clinic (n = 50). Of these, 38% were vitamin D-insufficient (<75 nM 25OHD) and received supplementation with vitamin D (50,000 IU vitamin D2 twice weekly for 5 wk). Baseline 25OHD status or vitamin D supplementation had no effect on circulating levels of hCAP. Therefore, ex vivo changes in hCAP for each subject were assessed using peripheral blood monocytes cultured with 10% autologous serum (n = 28). Under these vitamin D “insufficient” conditions the TLR2/1 ligand 19 kDa lipopeptide or the TLR4 ligand LPS, monocytes showed increased expression of the vitamin D-activating enzyme CYP27b1 (5- and 5.5-fold, respectively, both p < 0.01) but decreased expression of hCAP mRNA (10-fold and 30-fold, both p < 0.001). Following treatment with 19 kDa, expression of hCAP: 1) correlated with 25OHD levels in serum culture supplements (R = 0.649, p < 0.001); 2) was significantly enhanced by exogenous 25OHD (5 nM); and 3) was significantly enhanced with serum from vivo vitamin D-supplemented patients. These data suggest that a key role of vitamin D in innate immunity is to maintain localized production of antibacterial hCAP following TLR activation of monocytes.
Design of a Reliability Model under Different Fault based Parameters

Software fault analysis is on major vector adopted by different researchers to analyze the software reliability. But most of the author taken the fault individually as the fault criticality or the fault count. But in this presented work we have considered all aspects of software faults i.e. fault count, fault criticality, fault frequency, associatively between faults. In this work a three level structure is been defined to perform the fault based analysis. At first level, individual fault and fault criticality is analyzed where as in second level fault-module associatively and fault-fault associatively is discussed. At third level, the complexity of the module will be identified. Finally, all factors will be combined to identify the overall complexity and severity of the module and the system. As the work is based on all aspects of faults as well as metric based complexity, so that high level reliability and accuracy is expected from the system.
Modelling Term Dependence with Copulas

Many generative language and relevance models assume conditional independence between the likelihood of observing individual terms. This assumption is obviously naive, but also hard to replace or relax. There are only very few term pairs that actually show significant conditional dependencies while the vast majority of co-located terms has no implications on the document's topical nature or relevance towards a given topic. It is exactly this situation that we capture in a formal framework: A limited number of meaningful dependencies in a system of largely independent observations. Making use of the formal copula framework, we describe the strength of causal dependency in terms of a number of established term co-occurrence metrics. Our experiments based on the well known ClueWeb'12 corpus and TREC 2013 topics indicate significant performance gains in terms of retrieval performance when we formally account for the dependency structure underlying pieces of natural language text.
Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy

Abstract Muscle loss during aging and disuse is a highly prevalent and disabling condition, but knowledge about cellular pathways mediating muscle atrophy is still limited. Given the postmitotic nature of skeletal myocytes, the maintenance of cellular homeostasis relies on the efficiency of cellular quality control mechanisms. In this scenario, alterations in mitochondrial function are considered a major factor underlying sarcopenia and muscle atrophy. Damaged mitochondria are not only less bioenergetically efficient, but also generate increased amounts of reactive oxygen species, interfere with cellular quality control mechanisms, and display a greater propensity to trigger apoptosis. Thus, mitochondria stand at the crossroad of signaling pathways that regulate skeletal myocyte function and viability. Studies on these pathways have sometimes provided unexpected and counterintuitive results, which suggests that they are organized into a complex, heterarchical network that is currently insufficiently understood. Untangling the complexity of such a network will likely provide clinicians with novel and highly effective therapeutics to counter the muscle loss associated with aging and disuse. In this review, we summarize the current knowledge on the mechanisms whereby mitochondrial dysfunction intervenes in the pathogenesis of sarcopenia and disuse atrophy, and highlight the prospect of targeting specific processes to treat these conditions.
Subcellular mRNA localisation at a glance

ABSTRACT mRNA localisation coupled to translational regulation provides an important means of dictating when and where proteins function in a variety of model systems. This mechanism is particularly relevant in polarised or migrating cells. Although many of the models for how this is achieved were first proposed over 20 years ago, some of the molecular details are still poorly understood. Nevertheless, advanced imaging, biochemical and computational approaches have started to shed light on the cis-acting localisation signals and trans-acting factors that dictate the final destination of localised transcripts. In this Cell Science at a Glance article and accompanying poster, we provide an overview of mRNA localisation, from transcription to degradation, focusing on the microtubule-dependent active transport and anchoring mechanism, which we will use to explain the general paradigm. However, it is clear that there are diverse ways in which mRNAs become localised and target protein expression, and we highlight some of the similarities and differences between these mechanisms.