Miracle-dz/UniFAR-FTUs huggingface dataset:
Small leucine-rich proteoglycans in atherosclerotic lesions: novel targets of chronic statin treatment?

Small leucine‐rich proteoglycans (SLRPs), such as decorin and biglycan, regulate the assembly and turnover of collagenous matrix. The aim of the study was to analyse the effect of chronic rosuvastatin treatment on decorin, biglycan and the collagen matrix in ApoE‐deficient mice. Twenty‐week‐old male ApoE‐deficient mice received normal chow or 20 mg rosuvastatin/kg × day for 32 weeks. Subsequently, matrix composition was analysed by histochemistry and immunostaining at the aortic root and in innominate arteries of ApoE deficient mice as well as in human carotid endarterectomy specimens. Immunoblotting of proteoglycans was performed from aortic extracts of ApoE‐deficient mice. Immunohistochemistry and immunoblotting revealed strongly increased decorin and biglycan deposition in atherosclerotic plaques at the aortic root and in innominate arteries. In contrast, versican and perlecan expression was not changed by rosu‐vastatin. Furthermore, matrix metalloproteinase 2 and gelatinolytic activity were decreased in response to rosuvastatin and a condensed collagen‐rich matrix was formed. In carotid endarterectomy specimens of statin‐treated patients increased decorin and biglycan accumulation was detected as well. Drug treatment did not change low‐density lipoprotein (LDL) plasma levels in ApoE‐deficient mice and did not significantly affect lipid retention at the aortic root level as demonstrated by oil‐red O staining and immunohistochemistry of LDL. Long‐term treatment with rosuvastatin caused pronounced remodelling of atherosclerotic plaque matrix characterized specifically by enrichment with SLRPs and formation of a condensed collagen matrix. Therefore, decorin and biglycan might represent novel targets of statin treatment that contribute to a stable plaque phenotype.
A spiking network model of cerebellar Purkinje cells and molecular layer interneurons exhibiting irregular firing

While the anatomy of the cerebellar microcircuit is well-studied, how it implements cerebellar function is not understood. A number of models have been proposed to describe this mechanism but few emphasize the role of the vast network Purkinje cells (PKJs) form with the molecular layer interneurons (MLIs)—the stellate and basket cells. We propose a model of the MLI-PKJ network composed of simple spiking neurons incorporating the major anatomical and physiological features. In computer simulations, the model reproduces the irregular firing patterns observed in PKJs and MLIs in vitro and a shift toward faster, more regular firing patterns when inhibitory synaptic currents are blocked. In the model, the time between PKJ spikes is shown to be proportional to the amount of feedforward inhibition from an MLI on average. The two key elements of the model are: (1) spontaneously active PKJs and MLIs due to an endogenous depolarizing current, and (2) adherence to known anatomical connectivity along a parasagittal strip of cerebellar cortex. We propose this model to extend previous spiking network models of the cerebellum and for further computational investigation into the role of irregular firing and MLIs in cerebellar learning and function.
EGF-Like Growth Factors As Mediators of LH Action in the Ovulatory Follicle

Before ovulation in mammals, a cascade of events resembling an inflammatory and/or tissue remodeling process is triggered by luteinizing hormone (LH) in the ovarian follicle. Many LH effects, however, are thought to be indirect because of the restricted expression of its receptor. Here, we demonstrate that LH stimulation induces the transient and sequential expression of the epidermal growth factor (EGF) family members amphiregulin, epiregulin, and beta-cellulin. Incubation of follicles with these growth factors recapitulates the morphological and biochemical events triggered by LH, including cumulus expansion and oocyte maturation. Thus, these EGF-related growth factors are paracrine mediators that propagate the LH signal throughout the follicle.
Combining Centralised and Distributed Testing

Many systems interact with their environment at distributed interfaces (ports) and sometimes it is not possible to place synchronised local testers at the ports of the system under test (SUT). There are then two main approaches to testing: having independent local testers or a single centralised tester that interacts asynchronously with the SUT. The power of using independent testers has been captured using implementation relation dioco. In this article, we define implementation relation diococ for the centralised approach and prove that dioco and diococ are incomparable. This shows that the frameworks detect different types of faults and so we devise a hybrid framework and define an implementation relation diocos for this. We prove that the hybrid framework is more powerful than the distributed and centralised approaches. We then prove that the Oracle problem is NP-complete for diococ and diocos but can be solved in polynomial time if we place an upper bound on the number of ports. Finally, we consider the problem of deciding whether there is a test case that is guaranteed to force a finite state model into a particular state or to distinguish two states, proving that both problems are undecidable for the centralised and hybrid frameworks.
Evolution of Interferon-Based Therapy for Chronic Hepatitis C

Since 1986, interferon-alfa (IFN-α) monotherapy has been administered for patients with chronic hepatitis C (CHC). However, sustained response rate is only about 8% to 9%. Subsequent introduction of ribavirin in combination with IFN-α was a major breakthrough in the treatment of CHC. Sustained virological responses (SVRs) rate is about 30% in hepatitis C virus genotype 1 (HCV-1) patients, and is about 65% in HCV-2 or -3 patients. After 2000, pegylated interferon (PegIFN) much improved the rates of SVR. Presently, PegIFN-α-ribavirin combination therapy has been current standard of care for patients infected with HCV. In patients with HCV-1, treatment for 48 weeks is optimal, but 24 weeks of treatment is sufficient in HCV-2 or -3 infected patients. Clinical factors have been identified as predictors for the efficacy of the IFN-based therapy. The baseline factor most strongly predictive of an SVR is the presence of HCV-2 or -3 infections. Rapid virological response (RVR) is the single best predictor of an SVR to PegIFN-ribavirin therapy. If patients can't achieve a RVR but achieve a complete early virological response (cEVR), treatment with current standard of care can provide more than 90% SVR rate. HCV-1 patients who do not achieve an EVR should discontinue the therapy. Recent advances of protease inhibitor may contribute the development of a novel triple combination therapy.
In vivo whole‐blood T2 versus HbO2 calibration by modulating blood oxygenation level in the femoral vein through intermittent cuff occlusion

To investigate the feasibility of estimating calibration constants (K and T2o) in vivo for converting whole‐blood T2 to blood hemoglobin oxygen saturation (HbO2) according to the Luz‐Meiboom model, 1/T2=1/T2o+K(1−HbO2)2 , where K and T2o are relaxivity and transverse relaxation time of fully saturated blood, respectively.
The structure and evolution of story networks

With this study, we advance the understanding about the processes through which stories are retold. A collection of story retellings can be considered as a network of stories, in which links between stories represent pre-textual (or ancestral) relationships. This study provides a mechanistic understanding of the structure and evolution of such story networks: we construct a story network for a large diachronic collection of Dutch literary retellings of Red Riding Hood, and compare this network to one derived from a corpus of paper chain letters. In the analysis, we first provide empirical evidence that the formation of these story networks is subject to age-dependent selection processes with a strong lopsidedness towards shorter time-spans between stories and their pre-texts (i.e. ‘young’ story versions are preferred in producing new versions). Subsequently, we systematically compare these findings with and among predictions of various formal models of network growth to determine more precisely which kinds of attractiveness are also at play or might even be preferred as explicatory models. By carefully studying the structure and evolution of the two story networks, then, we show that existing stories are differentially preferred to function as a new version's pre-text given three types of attractiveness: (i) frequency-based and (ii) model-based attractiveness which (iii) decays in time.
Adaptive cartooning for privacy protection in camera networks

Visual privacy in video-based applications such as surveillance, assisted living or home monitoring is a highly active research topic. It is critical to protect the privacy of monitored people without severely limiting the utility of the system. We present a resource-aware cartooning privacy protection filter which converts raw images into abstracted frames where the privacy revealing details are removed. Cartooning can be applied either to entire images or pre-selected sensitive regions of interest. We provide an adaptation mechanism to our cartooning technique where the operator can easily change the filter intensity. The feasibility of this new approach is demonstrated by its deployment to real-world embedded smart cameras. We evaluate privacy protection and utility of cartooning with the PEViD data set and compare it with the two widely-used privacy filters: blurring and pixelation.
Social facilitation with social robots?

Regarding the future usage of social robots in workplace scenarios, we addressed the question of potential mere robotic presence effects on human performance. Applying the experimental social facilitation paradigm in social robotics, we compared task performance of 106 participants on easy and complex cognitive and motoric tasks across three presence groups (alone vs. human present vs. robot present). Results revealed significant evidence for the predicted social facilitation effects for both human and robotic presence compared to an alone condition. Implications of these findings are discussed with regard to the consideration of the interaction of robotic presence and task difficulty in modeling robotic assistance systems.
Local and Global Gating of Synaptic Plasticity

Mechanisms influencing learning in neural networks are usually investigated on either a local or a global scale. The former relates to synaptic processes, the latter to unspecific modulatory systems. Here we study the interaction of a local learning rule that evaluates coincidences of pre- and postsynaptic action potentials and a global modulatory mechanism, such as the action of the basal forebrain onto cortical neurons. The simulations demonstrate that the interaction of these mechanisms leads to a learning rule supporting fast learning rates, stability, and flexibility. Furthermore, the simulations generate two experimentally testable predictions on the dependence of backpropagating action potential on basal forebrain activity and the relative timing of the activity of inhibitory and excitatory neurons in the neocortex.
Mitochondrial Dysfunction Causes Cell Death in Patients Affected by Fragile-X-Associated Disorders

Mitochondria are involved in multiple aspects of neurodevelopmental processes and play a major role in the pathogenetic mechanisms leading to neuro-degenerative diseases. Fragile-X-related disorders (FXDs) are genetic conditions that occur due to the dynamic expansion of CGG repeats of the FMR1 gene encoding for the RNA-binding protein FMRP, particularly expressed in the brain. This gene expansion can lead to premutation (PM, 56–200 CGGs), full mutation (FM, >200 CGGs), or unmethylated FM (UFM), resulting in neurodegeneration, neurodevelopmental disorders, or no apparent intellectual disability, respectively. To investigate the mitochondrial mechanisms that are involved in the FXD patients, we analyzed mitochondrial morphology and bioenergetics in fibroblasts derived from patients. Donut-shaped mitochondrial morphology and excessive synthesis of critical mitochondrial proteins were detected in FM, PM, and UFM cells. Analysis of mitochondrial oxidative phosphorylation in situ reveals lower respiration in PM fibroblasts. Importantly, mitochondrial permeability transition-dependent apoptosis is sensitized to reactive oxygen species in FM, PM, and UFM models. This study elucidated the mitochondrial mechanisms that are involved in the FXD phenotypes, and indicated altered mitochondrial function and morphology. Importantly, a sensitization to permeability transition and apoptosis was revealed in FXD cells. Overall, our data suggest that mitochondria are novel drug targets to relieve the FXD symptoms.
A nationally representative case-control study of smoking and death in India.

BACKGROUND The nationwide effects of smoking on mortality in India have not been assessed reliably. METHODS In a nationally representative sample of 1.1 million homes, we compared the prevalence of smoking among 33,000 deceased women and 41,000 deceased men (case subjects) with the prevalence of smoking among 35,000 living women and 43,000 living men (unmatched control subjects). Mortality risk ratios comparing smokers with nonsmokers were adjusted for age, educational level, and use of alcohol. RESULTS About 5% of female control subjects and 37% of male control subjects between the ages of 30 and 69 years were smokers. In this age group, smoking was associated with an increased risk of death from any medical cause among both women (risk ratio, 2.0; 99% confidence interval [CI], 1.8 to 2.3) and men (risk ratio, 1.7; 99% CI, 1.6 to 1.8). Daily smoking of even a small amount of tobacco was associated with increased mortality. Excess deaths among smokers, as compared with nonsmokers, were chiefly from tuberculosis among both women (risk ratio, 3.0; 99% CI, 2.4 to 3.9) and men (risk ratio, 2.3; 99% CI, 2.1 to 2.6) and from respiratory, vascular, or neoplastic disease. Smoking was associated with a reduction in median survival of 8 years for women (99% CI, 5 to 11) and 6 years for men (99% CI, 5 to 7). If these associations are mainly causal, smoking in persons between the ages of 30 and 69 years is responsible for about 1 in 20 deaths of women and 1 in 5 deaths of men. In 2010, smoking will cause about 930,000 adult deaths in India; of the dead, about 70% (90,000 women and 580,000 men) will be between the ages of 30 and 69 years. Because of population growth, the absolute number of deaths in this age group is rising by about 3% per year. CONCLUSIONS Smoking causes a large and growing number of premature deaths in India.
The identification of a novel synaptosomal-associated protein, SNAP-25, differentially expressed by neuronal subpopulations

cDNA clones of a neuronal-specific mRNA encoding a novel 25-kD synaptosomal protein, SNAP-25, that is widely, but differentially expressed by diverse neuronal subpopulations of the mammalian nervous system have been isolated and characterized. The sequence of the SNAP- 25 cDNA revealed a single open reading frame that encodes a primary translation product of 206 amino acids. Antisera elicited against a 12- amino acid peptide, corresponding to the carboxy-terminal residues of the predicted polypeptide sequence, recognized a single 25-kD protein that is associated with synaptosomal fractions of hippocampal preparations. The SNAP-25 polypeptide remains associated with synaptosomal membrane components after hypoosmotic lysis and is released by nonionic detergent but not high salt extraction. Although the SNAP-25 polypeptide lacks a hydrophobic stretch of residues compatible with a transmembrane region, the amino terminus may form an amphiphilic helix that may facilitate alignment with membranes. The predicted amino acid sequence also includes a cluster of four closely spaced cysteine residues, similar to the metal binding domains of some metalloproteins, suggesting that the SNAP-25 polypeptide may have the potential to coordinately bind metal ions. Consistent with the protein fractionation, light and electron microscopic immunocytochemistry indicated that SNAP-25 is located within the presynaptic terminals of hippocampal mossy fibers and the inner molecular layer of the dentate gyrus. The mRNA was found to be enriched within neurons of the neocortex, hippocampus, piriform cortex, anterior thalamic nuclei, pontine nuclei, and granule cells of the cerebellum. The distribution of the SNAP-25 mRNA and the association of the protein with presynaptic elements suggest that SNAP-25 may play an important role in the synaptic function of specific neuronal systems.
Biogenesis of Mitochondria: Analysis of Deletion of Mitochondrial Antibiotic Resistance Markers in Petite Mutants of Saccharomyces cerevisiae

Yeast strains carrying markers in several mitochondrial antibiotic resistance loci have been employed in a study of the retention and deletion of mitochondrial genes in cytoplasmic petite mutants. An assessment is made of the results in terms of the probable arrangement and linkage of mitochondrial genetic markers. The results are indicative of the retention of continuous stretches of the mitochondrial genome in most petite mutants, and it is therefore possible to propose a gene order based on co-retention of different markers. The order par, mik1, oli1 is suggested from the petite studies in the case of three markers not previously assigned an unambiguous order by analysis of mitochondrial gene recombination. The frequency of separation of markers by deletion in petites was of an order similar to that obtained by recombination in polar crosses, except in the case of the ery1 and cap1 loci, which were rarely separated in petite mutants. The deletion or retention of the locus determining polarity of recombination (ω) was also demonstrated and shown to coincide with deletion or retention of the ery1, cap1 region of the mitochondrial genome. Petites retaining this region, when crossed with rho+ strains, display features of polarity of recombination and transmission similar to the parent rho+ strain. By contrast a petite determined to have lost the ω+ locus did not show normal polarity of marker transmission. Differences were observed in the relative frequency of retention of markers in a number of strains and also when comparing petites derived spontaneously with those obtained after ultraviolet light mutagenesis. By contrast, a similar pattern of marker retention was seen when comparing spontaneous with ethidium bromide-induced petites.
TAF4b and TAF4 differentially regulate mouse embryonic stem cells maintenance and proliferation

TAF4b is a cell type‐specific subunit of the general transcription factor TFIID. Here, we show that TAF4b is highly expressed in embryonic stem cells (ESC) and is down‐regulated upon differentiation. To examine the role of TAF4b in ESC, we applied a knockdown (KD) approach. TAF4b depletion is associated with morphological changes and reduced expression of the self‐renewal marker alkaline phosphatase. In contrast, KD of TAF4, a ubiquitously expressed TAF4b paralog, retained and even stabilized ESC stemness. Retinoic acid‐induced differentiation was facilitated in the absence of TAF4b but was significantly delayed by TAF4 KD. Furthermore, TAF4b supports, whereas TAF4 inhibits, ESC proliferation and cell cycle progression. We identified a subset of TAF4b target genes preferentially expressed in ESC and controlling the cell cycle. Among them are the germ cell‐specific transcription factor Sohlh2 and the protein kinase Yes1, which was recently shown to regulate ESC self‐renewal. Interestingly, Sohlh2 and Yes1 are also targets of the pluripotency factor Oct4, and their regulation by Oct4 is TAF4b‐dependent. Consistent with that, TAF4b but not TAF4 interacts with Oct4. Our findings suggest that TAF4b cooperates with Oct4 to regulate a subset of genes in ESC, whereas TAF4 is required for later embryonic developmental stages.
Treatment Satisfaction and Well-Being in Patients with Myopic Choroidal Neovascularization Treated with Ranibizumab in the REPAIR Study

The Ranibizumab for the Treatment of Choroidal Neovascularisation (CNV) Secondary to Pathological Myopia (PM): an Individualized Regimen (REPAIR) trial was a prospective study exploring the efficacy and safety of intravitreal ranibizumab 0.5 mg using an individualized treatment regimen over 12 months. The current study investigated the impact of treatment with ranibizumab as needed (pro re nata [PRN]) on individuals with myopic choroidal neovascularization (mCNV) in the REPAIR study, using patient-reported outcome measures (PROMs) for treatment satisfaction and well-being. This study included 65 adults with mCNV and a best-corrected visual acuity (BCVA) letter score of 24–78 in the study eye. Patients completed the Macular Disease Treatment Satisfaction Questionnaire (MacTSQ) at months 1, 6 and 12, and the 12-item Well-Being Questionnaire (W-BQ12) at baseline and months 1, 6 and 12. Subgroup analyses investigated the relationship between PROM scores and treatment in the better- or worse-seeing eye (BSE/WSE), number of injections received, baseline BCVA, BCVA improvement and age. Pearson correlations between change in BCVA, MacTSQ scores and W-BQ12 scores were calculated. The main outcome measures were treatment satisfaction measured with the MacTSQ (score 0–72) and well-being measured with the W-BQ12 (score 0–36). Treatment satisfaction significantly increased over the study period (p = 0.0001). Mean MacTSQ scores increased by 9.7 and 10.0 in patients treated in their WSE and BSE, respectively. Treatment satisfaction was highest in individuals receiving only one injection at month 1; however, by month 12, scores were similar across injection subgroups. Patients aged 68 years or older had the highest MacTSQ scores. Well-being scores also significantly increased over the study period (p = 0.03). Mean W-BQ12 scores increased by 1.7 in patients treated in their WSE and by 2.1 in patients treated in their BSE. Individuals aged 40 years or younger had the greatest increases in general well-being. Patients who experienced stable or improved BCVA at month 12 had greater increases in W-BQ12 scores than those who experienced a decrease. Correlations between BCVA, MacTSQ scores and W-BQ12 scores were largely non-significant. In conclusion, treatment satisfaction and well-being increased during treatment with ranibizumab PRN. Although directly comparable data are limited for the MacTSQ and W-BQ12 in mCNV, these results complement PROM outcomes reported in related studies.
A Speech Corpus for Dyslexic Reading Training

Traditional Danish reading training for dyslexic readers typically involves the presence of a professional reading therapist for guidance, advice and evaluation. Allowing dyslexic readers to train their reading skills on their own could not only benefit the dyslexics themselves in terms of increased flexibility but could also allow professional therapists to increase the amount of dyslexic readers to whom they have a professional contact. It is envisioned that an automated reading training tool operating on the basis of ASR could provide dyslexic users with such independence. However, only limited experience in handling dyslexic input (in Danish) by a speech recognizer exists currently. This paper reports on the establishment of a speech corpus of Danish dyslexic speech along with an annotation hereof and the setup of a proof-of-concept training tool allowing dyslexic users to improve their reading skills on their own. Despite relatively limited ASR performance, a usability evaluation by dyslexic users shows an unconditional belief in the fairness of the system and indicates furthermore willingness for using such a training tool.