Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeted deletion of Dicer disrupts lens morphogenesis, corneal epithelium stratification, and whole eye development

Dicer, a ribonuclease essential for miRNA processing, is expressed abundantly in developing mouse cornea and lens. We studied the roles of Dicer and miRNAs in eye development by conditionally deleting the Dicer gene in the mouse lens and corneal epithelium. Adult Dicer conditional null (DicerCN) mice had severe microphthalmia with no discernible lens and a poorly stratified corneal epithelium. Targeted deletion of Dicer effectively inhibited miRNA processing in the developing lens at 12.5 day of embryogenesis (E12.5). Lens development initiated normally but underwent progressive dystrophy between E14.5 and E18.5. Microarray analysis revealed activation of P53 signaling in DicerCN lenses at E13.5, consistent with increased apoptosis and reduced cell proliferation between E12.5 and E14.5. Expression of Pax6 and other lens developmental transcription factors were not greatly affected between E12.5 and E14.5 but decreased as the lens degenerated. Our data indicated an indispensible role for Dicer and miRNAs in lens and corneal development. Developmental Dynamics 238:2388–2400, 2009. © 2009 Wiley‐Liss, Inc.
Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers.

BACKGROUND Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility. A genome-wide association study recently identified an association between the rare allele of the single-nucleotide polymorphism (SNP) rs3814113 (ie, the C allele) at 9p22.2 and decreased risk of ovarian cancer for women in the general population. We evaluated the association of this SNP with ovarian cancer risk among BRCA1 or BRCA2 mutation carriers by use of data from the Consortium of Investigators of Modifiers of BRCA1/2. METHODS We genotyped rs3814113 in 10,029 BRCA1 mutation carriers and 5837 BRCA2 mutation carriers. Associations with ovarian and breast cancer were assessed with a retrospective likelihood approach. All statistical tests were two-sided. RESULTS The minor allele of rs3814113 was associated with a reduced risk of ovarian cancer among BRCA1 mutation carriers (per-allele hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.72 to 0.85; P = 4.8 × 10(-9)) and BRCA2 mutation carriers (hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.67 to 0.90; P = 5.5 × 10(-4)). This SNP was not associated with breast cancer risk among either BRCA1 or BRCA2 mutation carriers. BRCA1 mutation carriers with the TT genotype at SNP rs3814113 were predicted to have an ovarian cancer risk to age 80 years of 48%, and those with the CC genotype were predicted to have a risk of 33%. CONCLUSION Common genetic variation at the 9p22.2 locus was associated with decreased risk of ovarian cancer for carriers of a BRCA1 or BRCA2 mutation.
Automatic path-planning algorithm maximizing observation area for virtual colonoscopy

To navigate a colon lumen, a proper camera path should be generated prior to the navigation. Conventional path-planning algorithms try to find an accurate and robust centerline by assuming that a centerline of colon lumen is the best choice for camera path. For efficient and reliable navigation, however, the centerline may not minimize unobservable area from the camera path. In this paper, we first define a new coverage measure reflecting the temporal visibility. And based on this measure, a fast and efficient path-planning algorithm is proposed to increase the visibility coverage. The proposed algorithm first simplifies the object surface using the centerline determined. Then, camera view positions and directions are estimated to maximize the observable surface. Simulation results prove that the proposed algorithm provides a better coverage rate than the conventional one without a significant increase of additional computation.
Autophagy in neurodegenerative diseases: pathogenesis and therapy

The most prevalent pathological features of many neurodegenerative diseases are the aggregation of misfolded proteins and the loss of certain neuronal populations. Autophagy, as major intracellular machinery for degrading aggregated proteins and damaged organelles, has been reported to be involved in the occurrence of pathological changes in many neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. In this review, we summarize most recent research progress in this topic and provide a new perspective regarding autophagy regulation on the pathogenesis of neurodegenerative diseases. Finally, we discuss the signaling molecules in autophagy‐related pathways as therapeutic targets for the treatment of these diseases.
Metabotropic glutamate receptor signaling is required for NMDA receptor-dependent ocular dominance plasticity and LTD in visual cortex

Significance Interruption of normal sensory experience during early postnatal life often causes a permanent loss of synaptic strength in the brain and consequent functional impairment. For example, temporary monocular deprivation causes long-term depression (LTD) of synapses in the visual cortex of mammals, along with a profound loss of vision. The mechanisms by which this synaptic plasticity occurs are only partially understood. Here we show that signaling via metabotropic glutamate receptor 5 during a critical period of postnatal development establishes the biochemical conditions that are permissive for activity-dependent sculpting of excitatory synapses via the mechanism of NMDA receptor-dependent LTD. A feature of early postnatal neocortical development is a transient peak in signaling via metabotropic glutamate receptor 5 (mGluR5). In visual cortex, this change coincides with increased sensitivity of excitatory synapses to monocular deprivation (MD). However, loss of visual responsiveness after MD occurs via mechanisms revealed by the study of long-term depression (LTD) of synaptic transmission, which in layer 4 is induced by acute activation of NMDA receptors (NMDARs) rather than mGluR5. Here we report that chronic postnatal down-regulation of mGluR5 signaling produces coordinated impairments in both NMDAR-dependent LTD in vitro and ocular dominance plasticity in vivo. The data suggest that ongoing mGluR5 signaling during a critical period of postnatal development establishes the biochemical conditions that are permissive for activity-dependent sculpting of excitatory synapses via the mechanism of NMDAR-dependent LTD.
Moral hypocrisy, moral inconsistency, and the struggle for moral integrity.

If future archaeologists unearthed an untitled social psychology textbook, its cover eaten by discerning worms, they would have to figure out what social psychologists studied from the papers they most prominently featured and the topics that recurrently received the field's attention. One reasonable hypothesis might be that ours was the science of moral hypocrisy. Social psychologists are suspicious of actors' self-reported motives, in part because people are surprisingly unaware of their actual motives (Nisbett & Wilson, 1977), but also because two central features of the social psychological model of human behavior, that people care deeply about making a good impression on others (e.g. Schlenker, 1980) and also wish to hold positive views of themselves (e.g., Greenwald, 1980), contribute to their claiming purer moral intentions than they actually have. More than any other social scientists, social psychologists make a living by showing that proclaimed moral intentions cannot be taken at face value. Distinguishing Moral Hypocrisy and Moral Inconsistency Hypocrisy is often defined in social psychology as not " practicing what you preach "
Desviación Constructiva, Intercambio Líder-Miembro y Confianza en la Evaluación: ¿Cómo se Interrelacionan, si lo Hacen?

This study examined connections between elements of Leader-Member-Exchange (LMX) relationships, trust and confidence in performance appraisal processes, and constructive deviant behavior. The sample consisted of 120 members of a large public service organization. The results support positive connections between the constructs of LMX, confidence in appraisal processes, and constructive deviant behaviors. However, when predicting constructive deviance we found no difference in using confidence in appraisal processes as a single predictor compared to using both confidence in appraisal and LMX. The implications of these results are discussed, and we offer several suggestions for developing research programs dealing with the intersection of LMX, confidence in appraisal processes, and constructive deviant behavior in organizations.
Application of nonparametric quantile regression to body mass index percentile curves from survey data

Increasing rates of overweight among children in the U.S. stimulated interest in obtaining national percentile curves of body size to serve as a benchmark in assessing growth development in clinical and population settings. In 2000, the U.S. Centers for Disease Control and Prevention (CDC) developed conditional percentile curves for body mass index (BMI) for ages 2–20 years. The 2000 CDC BMI‐for‐age curves are partially parametric and only partially incorporated the survey sample weights in the curve estimation. As a result, they may not fully reflect the underlying pattern of BMI‐for‐age in the population. This motivated us to develop a nonparametric double‐kernel‐based method and automatic bandwidth selection procedure. We include sample weights in the bandwidth selection, conduct median correction to reduce small‐sample smoothing bias, and rescale the bandwidth to make it scale invariant. Using this procedure we re‐estimate the national percentile BMI‐for‐age curves and the prevalence of high‐BMI children in the U.S. Copyright © 2009 John Wiley & Sons, Ltd.
Chromosome 8p tumor suppressor genes SH2D4A and SORBS3 cooperate to inhibit interleukin‐6 signaling in hepatocellular carcinoma

Several chronic inflammatory liver diseases, e.g., chronic hepatitis B or C viral infection and steatohepatitis, have been shown to predispose to the development of hepatocellular carcinoma (HCC). In patients with chronic liver disease, interleukin‐6 (IL‐6) serum levels are elevated and increase even more when HCC develops. However, the impact and regulatory mechanisms of IL‐6 signaling during hepatocarcinogenesis are still poorly defined. Here, we show that gene expression profiles of patients with chromosome 8p loss correlate with increased IL‐6 signaling. In addition, the chromosome 8p tumor suppressor genes Src homology 2 domain containing 4A (SH2D4A) and Sorbin and Src homology 3 domain containing 3 (SORBS3) together exerted greater inhibition of cell growth and clonogenicity compared to a single gene. Overexpression of SH2D4A and SORBS3 in HCC cells led to decreased IL‐6 target gene expression and reduced signal transducer and activator of transcription 3 (STAT3) signaling. In situ and in vitro coimmunoprecipitation assays revealed that SH2D4A directly interacts with STAT3, thereby retaining STAT3 in the cytoplasm and inhibiting STAT3 transcriptional activity. On the other hand, SORBS3 coactivated estrogen receptor α signaling, leading indirectly to repression of STAT3 signaling. In human HCC tissues, SH2D4A was positively associated with infiltrating regulatory and cytotoxic T‐cell populations, suggesting distinct immunophenotypes in HCC subgroups with chromosome 8p loss. Thus, the genetically linked tumor suppressors SH2D4A and SORBS3 functionally cooperate to inhibit STAT3 signaling in HCC. Conclusion: The chromosome 8p tumor suppressor genes SORBS3 and SH2D4A are physically and functionally linked and provide a molecular mechanism of inhibiting STAT3‐mediated IL‐6 signaling in HCC cells. (Hepatology 2016;64:828‐842)
Income Status and Education as Predictors of HIV Transmission in South Africa

The global Human Immunodeficiency Virus (HIV) epidemic targets various populations around the world, and South Africa is one of a number of countries where prevalence rates of the virus continue to increase despite the introduction of a viable treatment option. Previously investigated implications of HIV in South Africa are primarily related to its effects on the health-care sector of the country. However, complex socioeconomic processes are relevant to the discussion of HIV-related risk factors and consequences affecting individuals and households within South Africa. A large body of literature covers many socioeconomic perspectives on HIV, including the effect of socioeconomic status on HIV infection. While the roles of income status and education as risk factors for HIV infection have been explored extensively in a South African context, the connection between this and consequent adverse impacts on these factors as a result of HIV infection has not been clearly identified. This paper aims to address the gap in the literature regarding how specific socioeconomic factors act as risk factors for HIV contraction, but also how the same factors are affected as an associated outcome in those infected with HIV. Specifically, this paper argues that income status and education act as risk factors for HIV through their effects on individual behaviour, while also being adversely impacted due to the occurrence of infection. These impacts on income status and education contribute to South Africa’s inability to stop perpetuating the cycle of HIV prevalence.
Time‐related changes in firing rates are influenced by recruitment threshold and twitch force potentiation in the first dorsal interosseous

What is the central question of this study? The influences of motor unit recruitment threshold and twitch force potentiation on the changes in firing rates during steady‐force muscular contractions are not well understood. What is the main finding and its importance? The behaviour of motor units during steady force was influenced by recruitment threshold, such that firing rates decreased for lower‐threshold motor units but increased for higher‐threshold motor units. In addition, individuals with greater changes in firing rates possessed greater twitch force potentiation.
13 Genome Based Vaccines Against Parasites

In its original concept, vaccination aims to mimic the development of naturally acquired immunity by inoculation of nonpathogenic but still immunogenic components of the pathogen in question, or closely related organisms. Vaccination is one of the most effective tools allowing near or complete eradication of fatal diseases. In recent times, vaccination was based on conventional approaches that were successful in several diseases but they require the pathogen to be grown in laboratory conditions, are time-consuming and allow for the identification of only the most abundant antigens, which can be purified in quantities suitable for vaccine testing. The conventional approach to vaccine development uses two methods: first, attenuation of pathogens by serial passages in vitro to obtain live-attenuated strains to be used as vaccines, and second, identification of protective antigens to be used in non-living, subunit vaccines. Using conventional vaccinology, vaccines targeting pathogens with low antigenic variability and those for which protection depends on antibody mediated immunity like polio, MMR, Tetanus, Influenza, and Diptheria, had been licensed. Furthermore, if we are dealing with non-cultivatable microorganisms or have high antigenic variability or need T cell-dependent induced immunity like MenB, TB, HIV, Hepatitis B & C, Malaria and parasite diseases, there is no advance to development a specific vaccine. With the development of the DNA sequencing technologies in the 1970s till recent years, we observed the completion of the sequencing of the genome of humans, a number of invertebrate species including Drosophila melanogaster and Caenorhabditis elegans and expanding number of microbial pathogens of medical and economic importance (Dalton et al., 2003). Expansion of these sequence information developed new approaches to decode, analyze and share these massive genetic data. The most widely used term for these approaches is the genomics. Genomics, studying the genome of organisms as a whole, and postgenomics technologies including investigating RNA (transcriptomics), proteins (proteomics), identification of immunogenic proteins (immunomics) and metabolites (metabolomics), have had a considerable impact in all areas of biological research (Bambini and Rappuoli, 2009), and the field of vaccinology is no exception. There are many examples using these approaches to develop vaccines but this chapter will focus on the possible genome based approaches to confer vaccine developed immunity against two examples of endoand ecto-parasites such as malaria and ticks, respectively.
A Local Algorithm for Structure-Preserving Graph Cut

Nowadays, large-scale graph data is being generated in a variety of real-world applications, from social networks to co-authorship networks, from protein-protein interaction networks to road traffic networks. Many existing works on graph mining focus on the vertices and edges, with the first-order Markov chain as the underlying model. They fail to explore the high-order network structures, which are of key importance in many high impact domains. For example, in bank customer personally identifiable information (PII) networks, the star structures often correspond to a set of synthetic identities; in financial transaction networks, the loop structures may indicate the existence of money laundering. In this paper, we focus on mining user-specified high-order network structures and aim to find a structure-rich subgraph which does not break many such structures by separating the subgraph from the rest. A key challenge associated with finding a structure-rich subgraph is the prohibitive computational cost. To address this problem, inspired by the family of local graph clustering algorithms for efficiently identifying a low-conductance cut without exploring the entire graph, we propose to generalize the key idea to model high-order network structures. In particular, we start with a generic definition of high-order conductance, and define the high-order diffusion core, which is based on a high-order random walk induced by user-specified high-order network structure. Then we propose a novel High-Order Structure-Preserving LOcal Cut (HOSPLOC) algorithm, which runs in polylogarithmic time with respect to the number of edges in the graph. It starts with a seed vertex and iteratively explores its neighborhood until a subgraph with a small high-order conductance is found. Furthermore, we analyze its performance in terms of both effectiveness and efficiency. The experimental results on both synthetic graphs and real graphs demonstrate the effectiveness and efficiency of our proposed HOSPLOC algorithm.
Sulfation of a High Endothelial Venule–Expressed Ligand for L-Selectin

During lymphocyte homing, L-selectin mediates the tethering and rolling of lymphocytes on high endothelial venules (HEVs) in secondary lymphoid organs. The L-selectin ligands on HEV are a set of mucin-like glycoproteins, for which glycosylation-dependent cell adhesion molecule 1 (GlyCAM-1) is a candidate. Optimal binding in equilibrium measurements requires sulfation, sialylation, and fucosylation of ligands. Analysis of GlyCAM-1 has revealed two sulfation modifications (galactose [Gal]-6-sulfate and N-acetylglucosamine [GlcNAc]-6-sulfate) of sialyl Lewis x. Recently, three related sulfotransferases (keratan sulfate galactose-6-sulfotransferase [KSGal6ST], high endothelial cell N-acetylglucosamine-6-sulfotransferase [GlcNAc6ST], and human GlcNAc6ST) were cloned, which can generate Gal-6-sulfate and GlcNAc-6-sulfate in GlyCAM-1. Imparting these modifications to GlyCAM-1, together with appropriate fucosylation, yields enhanced rolling ligands for both peripheral blood lymphocytes and Jurkat cells in flow chamber assays as compared with those generated with exogenous fucosyltransferase. Either sulfation modification results in an increased number of tethered and rolling lymphocytes, a reduction in overall rolling velocity associated with more frequent pausing of the cells, and an enhanced resistance of rolling cells to detachment by shear. All of these effects are predicted to promote the overall efficiency of lymphocyte homing. In contrast, the rolling interactions of E-selectin transfectants with the same ligands are not affected by sulfation.
Research Online Research Online Towards dynamic formation of temporal constraints for the service level Towards dynamic formation of temporal constraints for the service level agreements negotiation agreements negotiation

Abstract SLAs play an important role for the QoS-driven service composition. Meanwhile, the temporal constraints are one of the main elements in the management of SLA especially in specifying the validity period of the QoS offers. In practice, the temporal constraints should be generated dynamically by taking the resource capability of the provider into account. The generation should consider various parameters that influence the resource capability such as the expected duration of the required Web service, the amount of current utilization, the amount of available resources, the number of required time slots, etc. Therefore, this paper aims to elaborate this issue and present a temporal constraints formation for SLA negotiation framework. This framework is proposed in the context of service selection and SLA negotiation. It provides the foundation towards the dynamic formation. This paper also demonstrates the initial approach of temporal constraints formation. Abstract —SLAs play an important role for the QoS-driven service composition. Meanwhile, the temporal constraints are one of the main elements in the management of SLA especially in specifying the validity period of the QoS offers. In practice, the temporal constraints should be generated dynamically by taking the resource capability of the provider into account. The generation should consider various parameters that inﬂuence the resource capability such as the expected duration of the required Web service, the amount of current utilization, the amount of available resources, the number of required time slots, etc. Therefore, this paper aims to elaborate this issue and present a temporal constraints formation for SLA negotiation framework. This framework is proposed in the context of service selection and SLA negotiation. It provides the foundation towards the dynamic formation. This paper also demonstrates the initial approach of temporal constraints formation.
Medical Cannabis

Medical cannabis is a topic of increasing debate. To investigate this issue, we conducted a content analysis of Israeli news coverage of medical cannabis from 2007 to 2013. A deductive framing analysis examined three elite issue frames—medical, policy, and law enforcement. Additionally, inductive analysis revealed a a fourth, nonelite patients’ frame. Each frame was associated with a distinct pattern of textual elements, including portrayal of patients, references to cannabis, opinion about medical cannabis, and salience of scientific research. The most common and most stable frame was the policy frame. Implications for framing theory are discussed.
Model checking Markov reward models with impulse rewards

This paper considers model checking of Markov reward models (MRMs), continuous-time Markov chains with state rewards as well as impulse rewards. The reward extension of the logic CSL (continuous stochastic logic) is interpreted over such MRMs, and two numerical algorithms are provided to check the reachability of a set of goal states under a time and an accumulated reward constraint. This extends existing model-checking techniques for MRMs with just state rewards, and improves the applicability to thousands of states. Our approach is illustrated by using rewards for energy consumption in the setting of dynamic power management.