Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of Brainstem Pro-opiomelanocortin Neurons Produces Opioidergic Analgesia, Bradycardia and Bradypnoea

Opioids are widely used medicinally as analgesics and abused for hedonic effects, actions that are each complicated by substantial risks such as cardiorespiratory depression. These drugs mimic peptides such as β-endorphin, which has a key role in endogenous analgesia. The β-endorphin in the central nervous system originates from pro-opiomelanocortin (POMC) neurons in the arcuate nucleus and nucleus of the solitary tract (NTS). Relatively little is known about the NTSPOMC neurons but their position within the sensory nucleus of the vagus led us to test the hypothesis that they play a role in modulation of cardiorespiratory and nociceptive control. The NTSPOMC neurons were targeted using viral vectors in a POMC-Cre mouse line to express either opto-genetic (channelrhodopsin-2) or chemo-genetic (Pharmacologically Selective Actuator Modules). Opto-genetic activation of the NTSPOMC neurons in the working heart brainstem preparation (n = 21) evoked a reliable, titratable and time-locked respiratory inhibition (120% increase in inter-breath interval) with a bradycardia (125±26 beats per minute) and augmented respiratory sinus arrhythmia (58% increase). Chemo-genetic activation of NTSPOMC neurons in vivo was anti-nociceptive in the tail flick assay (latency increased by 126±65%, p<0.001; n = 8). All effects of NTSPOMC activation were blocked by systemic naloxone (opioid antagonist) but not by SHU9119 (melanocortin receptor antagonist). The NTSPOMC neurons were found to project to key brainstem structures involved in cardiorespiratory control (nucleus ambiguus and ventral respiratory group) and endogenous analgesia (periaqueductal gray and midline raphe). Thus the NTSPOMC neurons may be capable of tuning behaviour by an opioidergic modulation of nociceptive, respiratory and cardiac control.
Increased Levels of Multiresistant Bacteria and Resistance Genes after Wastewater Treatment and Their Dissemination into Lake Geneva, Switzerland

At present, very little is known about the fate and persistence of multiresistant bacteria (MRB) and their resistance genes in natural aquatic environments. Treated, but partly also untreated sewage of the city of Lausanne, Switzerland is discharged into Vidy Bay (Lake Geneva) resulting in high levels of contamination in this part of the lake. In the present work we have studied the prevalence of MRB and resistance genes in the wastewater stream of Lausanne. Samples from hospital and municipal raw sewage, treated effluent from Lausanne’s wastewater treatment plant (WTP) as well as lake water and sediment samples obtained close to the WTP outlet pipe and a remote site close to a drinking water pump were evaluated for the prevalence of MRB. Selected isolates were identified (16S rRNA gene fragment sequencing) and characterized with regards to further resistances, resistance genes, and plasmids. Mostly, studies investigating this issue have relied on cultivation-based approaches. However, the limitations of these tools are well known, in particular for environmental microbial communities, and cultivation-independent molecular tools should be applied in parallel in order to take non-culturable organisms into account. Here we directly quantified the sulfonamide resistance genes sul1 and sul2 from environmental DNA extracts using TaqMan real-time quantitative PCR. Hospital sewage contained the highest load of MRB and antibiotic resistance genes (ARGs). Wastewater treatment reduced the total bacterial load up to 78% but evidence for selection of extremely multiresistant strains and accumulation of resistance genes was observed. Our data clearly indicated pollution of sediments with ARGs in the vicinity of the WTP outlet. The potential of lakes as reservoirs of MRB and potential risks are discussed.
Auxin Dynamics after Decapitation Are Not Correlated with the Initial Growth of Axillary Buds1

One of the first and most enduring roles identified for the plant hormone auxin is the mediation of apical dominance. Many reports have claimed that reduced stem indole-3-acetic acid (IAA) levels and/or reduced basipetal IAA transport directly or indirectly initiate bud growth in decapitated plants. We have tested whether auxin inhibits the initial stage of bud release, or subsequent stages, in garden pea (Pisum sativum) by providing a rigorous examination of the dynamics of auxin level, auxin transport, and axillary bud growth. We demonstrate that after decapitation, initial bud growth occurs prior to changes in IAA level or transport in surrounding stem tissue and is not prevented by an acropetal supply of exogenous auxin. We also show that auxin transport inhibitors cause a similar auxin depletion as decapitation, but do not stimulate bud growth within our experimental time-frame. These results indicate that decapitation may trigger initial bud growth via an auxin-independent mechanism. We propose that auxin operates after this initial stage, mediating apical dominance via autoregulation of buds that are already in transition toward sustained growth.
Comparative Developmental Expression Profiling of Two C. elegans Isolates

Gene expression is known to change during development and to vary among genetically diverse strains. Previous studies of temporal patterns of gene expression during C. elegans development were incomplete, and little is known about how these patterns change as a function of genetic background. We used microarrays that comprehensively cover known and predicted worm genes to compare the landscape of genetic variation over developmental time between two isolates of C. elegans. We show that most genes vary in expression during development from egg to young adult, many genes vary in expression between the two isolates, and a subset of these genes exhibit isolate-specific changes during some developmental stages. This subset is strongly enriched for genes with roles in innate immunity. We identify several novel motifs that appear to play a role in regulating gene expression during development, and we propose functional annotations for many previously unannotated genes. These results improve our understanding of gene expression and function during worm development and lay the foundation for linkage studies of the genetic basis of developmental variation in gene expression in this important model organism.
The Role of Norepinephrine and Insulin Resistance in an Early Stage of Hypertension

The interrelationship between activity of sympathetic nervous system and metabolic risk factors in youth with hypertension (HT) has been poorly studied. The aim of our present study was to assess the interrelationship between metabolic risk factors, such as insulin resistance, concentration of plasminogen activator inhibitor (PAI)‐1, and catecholamines in an early stage of HT onset. An oral glucose tolerance test was performed in 17 young males with early‐diagnosed nontreated HT grade 1 and 16 gender‐, age‐, and BMI‐matched normotensive controls. Concentrations of glucose, insulin, epinephrine, norepinephrine, PAI‐1, and plasma renin activity (PRA) were determined in venous plasma. Insulin sensitivity indices (ISIs) proposed by Cederholm, Matsuda, and Gutt were calculated. HT had higher baseline levels of norepinephrine, insulin (P= 0.02), and PAI‐1 (P= 0.04). ISIs were lower in HT subjects (P < 0.001). Baseline concentrations of epinephrine were negatively associated with HDL cholesterol (r=−0.415, P= 0.02), ISI Matsuda (r=−0.361, P= 0.04), ISI Cederholm (r=−0.354, P= 0.04), and ISI Gutt (r=−0.429, P= 0.01), and positively with PRA (r= 0.609, P < 0.0001). Positive association was found between baseline concentrations of norepinephrine and PAI‐1 (r= 0.418, P= 0.02). The sympathetic overactivity, which occurs in the early stage of HT may contribute to reduced insulin sensitivity even in young patients and intensify the undesirable development of metabolic cardiovascular risk factors and progress of the disease.
Development and Validation of the Chinese Attitudes to Starting Insulin Questionnaire (Ch-ASIQ) for Primary Care Patients with Type 2 Diabetes

Objectives To develop and evaluate the psychometric properties of a Chinese questionnaire which assesses the barriers and enablers to commencing insulin in primary care patients with poorly controlled Type 2 diabetes. Research Design and Method Questionnaire items were identified using literature review. Content validation was performed and items were further refined using an expert panel. Following translation, back translation and cognitive debriefing, the translated Chinese questionnaire was piloted on target patients. Exploratory factor analysis and item-scale correlations were performed to test the construct validity of the subscales and items. Internal reliability was tested by Cronbach’s alpha. Results Twenty-seven identified items underwent content validation, translation and cognitive debriefing. The translated questionnaire was piloted on 303 insulin naïve (never taken insulin) Type 2 diabetes patients recruited from 10 government-funded primary care clinics across Hong Kong. Sufficient variability in the dataset for factor analysis was confirmed by Bartlett’s Test of Sphericity (P<0.001). Using exploratory factor analysis with varimax rotation, 10 factors were generated onto which 26 items loaded with loading scores > 0.4 and Eigenvalues >1. Total variance for the 10 factors was 66.22%. Kaiser-Meyer-Olkin measure was 0.725. Cronbach’s alpha coefficients for the first four factors were ≥0.6 identifying four sub-scales to which 13 items correlated. Remaining sub-scales and items with poor internal reliability were deleted. The final 13-item instrument had a four scale structure addressing: ‘Self-image and stigmatization’; ‘Factors promoting self-efficacy; ‘Fear of pain or needles’; and ‘Time and family support’. Conclusion The Chinese Attitudes to Starting Insulin Questionnaire (Ch-ASIQ) appears to be a reliable and valid measure for assessing barriers to starting insulin. This short instrument is easy to administer and may be used by healthcare providers and researchers as an assessment tool for Chinese diabetic primary care patients, including the elderly, who are unwilling to start insulin.
Eddy Amplitudes in Baroclinic Turbulence Driven by Nonzonal Mean Flow: Shear Dispersion of Potential Vorticity

Abstract As in the midlatitude atmosphere, midocean eddies are primarily generated by baroclinically unstable mean currents. In contrast to the atmosphere, however, oceanic currents are significantly nonzonal. Even weak nonzonal currents are linearly unstable since β does not suppress growing meridional waves. Theories for the nonlinear equilibration of baroclinic instability, and hence theories for the amplitudes of midocean eddies, must therefore take into account the different dynamics of nonzonal flow. It is shown here that the amplitude of fully developed baroclinic turbulence due to nonzonal shears differs from that due to zonal shears primarily in the nature of the eddy generation. Since β will act to create large-scale zonal jet structures regardless of the generation source, the nature of eddy fluxes of potential vorticity (the source of eddy energy) in the zonal and meridional directions are fundamentally different. The cross-jet mixing has been shown previously to obey a mixing-length scaling, .
Head Fixed Field Coil System For Measuring Eye Movements in Freely Moving Monkeys

Coil systems have been a standard for measuring eye movements. These systems, which have been designed to work at low frequencies (20 KHz), generally require large field coils so that a uniform field can be established at the eye coil site. This configuration makes it virtually impossible to study eye movements in freely moving animals. In this paper, we describe the design of a coil system, which operates at radio frequencies (10 MHz). This system allows the use of compact coils with radii of 10 mm that are capable of accurately measuring eye movements in three dimensions during head free locomotion. This system opens the possibility for studying eye movements in freely moving monkeys under a wide range of conditions
Subcellular distribution of rhodamine-actin microinjected into living fibroblastic cells

The time course and pattern of incorporation of rhodamine-labeled actin microinjected into cultured fibroblastic cells were examined by fluorescence microscopy. Following microinjection, the fluorescent probe was incorporated rapidly into ruffling membranes, and within 5 min faintly fluorescent stress fibers were observed. Levels of fluorescence in ruffling membranes then tended to remain constant while fluorescence of the stress fibers continued to increase until approximately 20-min postinjection. Small, discrete regions of some microinjected cells displayed high levels of fluorescence that appeared initially approximately 5-10 min postinjection. I observed these small areas of intense fluorescence frequently near the cell periphery, which corresponded to focal contacts when examined with interference reflection optics. The results of this study show that a relationship exists between patterns of fluorescent actin incorporation in these cells and cellular areas or structures presumed to play a role in cell movement. These findings suggest that actin within stress fibers and the microfilament network of ruffling membranes undergoes a rapid turnover that may relate directly to the motility of the cell.
Learning Optimal Features for Polyphonic Audio-to-Score Alignment

This paper addresses the design of feature functions for the matching of a musical recording to the symbolic representation of the piece (the score). These feature functions are defined as dissimilarity measures between the audio observations and template vectors corresponding to the score. By expressing the template construction as a linear mapping from the symbolic to the audio representation, one can learn the feature functions by optimizing the linear transformation. In this paper, we explore two different learning strategies. The first one uses a best-fit criterion (minimum divergence), while the second one exploits a discriminative framework based on a Conditional Random Fields model (maximum likelihood criterion). We evaluate the influence of the feature functions in an audio-to-score alignment task, on a large database of popular and classical polyphonic music. The results show that with several types of models, using different temporal constraints, the learned mappings have the potential to outperform the classic heuristic mappings. Several representations of the audio observations, along with several distance functions are compared in this alignment task. Our experiments elect the symmetric Kullback-Leibler divergence. Moreover, both the spectrogram and a CQT-based representation turn out to provide very accurate alignments, detecting more than 97% of the onsets with a precision of 100 ms with our most complex system.
Distinguishing AI from Male/Female Dialogue

Without knowledge of other features, can the sex of a person be determined through text-based communication alone? In the first Turing test experiment enclosing 24 human-duo set-ups embedded among machine-human pairs the interrogators erred 50% of the time in assigning the correct sex to a hidden interlocutor identified as human. In this paper we present five transcripts, in four gender blur occurred: Turing test interrogators misclassified male for female and vice versa. In the fifth, machine-human conversation artificial dialogue was branded as female teen. Did stereotypical views on male and female talk sway the judges to assign one way or another? This research is part of ongoing analysis of over 400 tests involving more than 80 human judges. Can we overcome unconscious bias and improve development of agent language?
Towards design pattern definition language

Design patterns are rapidly gaining acceptance in the software community not only as reusable constructs for software development but also for the documentation of the software architectural design. Most of the existing design pattern languages describe design patterns using a combination of a natural language, UML‐style diagrams and complex mathematical or logic based formalisms, which makes them hard for programmers to understand. In this paper we propose a design pattern definition language (DPDL) based on XML which can be used for sharing design patterns’ implementation details among developers. DPDL is easy to understand and use. It provides unambiguous description of the patterns and is extensible. DPDL also has the flexibility of defining design patterns in a generic term to be used as templates. Copyright © 2011 John Wiley & Sons, Ltd.
Cyanidin-3-rutinoside alleviates postprandial hyperglycemia and its synergism with acarbose by inhibition of intestinal α-glucosidase

The inhibitory activity on intestinal α-glucosidase by cyanidin-3-rutinoside was examined in vitro and in vivo. The IC50 values of cyanidin-3-rutinoside against intestinal maltase, and sucrase were 2,323 ± 14.8 and 250.2 ± 8.1 µM, respectively. The kinetic analysis revealed that intestinal sucrase was inhibited by cyanidin-3-rutinoside in a mixed-type manner. The synergistic inhibition also found in combination of cyanidin-3-rutinoside with acarbose against intestinal maltase and sucrase. The oral administration of cyanidin-3-rutinoside (100 and 300 mg/kg) plus maltose or sucrose to normal rats, postprandial plasma glucose was markedly suppressed at 30–90 min after loading. Furthermore, the normal rats treated with acarbose and cyanidin-3-rutinoside (30 mg/kg) showed greater reduction of postprandial plasma glucose than the group treated with acarbose alone. These results suggest that cyanidin-3-rutinoside retards absorption of carbohydrates by inhibition of α-glucosidase which may be useful as a potential inhibitor for prevention and treatment of diabetes mellitus.
Regulatory role of interleukin-10 and interferon-gamma in severe hepatic central and peripheral fibrosis in humans infected with Schistosoma japonicum.

BACKGROUND Schistosoma japonicum is the most pathogenic agent of hepatosplenic schistosomiasis. It causes fibrosis of the central (CentF) and peripheral (PerF) portal areas. We investigated whether CentF and PerF in Chinese fishermen infected with S. japonicum were associated with an abnormal production of cytokines and chemokines that, in experimental models, have been implicated in the regulation of fibrosis. METHODS Cytokines were measured by enzyme-linked immunosorbent assay in cultures of peripheral blood mononuclear cells from 127 patients, after stimulation with S. japonicum egg antigens. Data were analyzed by logistic regression that included age, sex, number of treatment episodes, alcohol use, and exposure as covariates. RESULTS CentF was associated with low levels of interleukin (IL)-10 (P= .0004), regulated on activation normally T cell expressed and secreted (P= .0004), and macrophage inflammatory protein-1alpha (P= .007). In a multivariate analysis, only IL-10 was associated with CentF (odds ratio [OR], 10.8; 95% confidence interval [CI], 3.2-38; P= .0004). Splenomegaly was also associated with low IL-10 production and, independently, with CentF. In multivariate analysis, PerF was associated with low production of interferon (IFN)-gamma (OR, 8.2; 95% CI, 2-33; P= .0035) but not with production of IL-10. CONCLUSIONS IL-10 is associated with protection against central fibrosis, because of its anti-inflammatory and antifibrosis effects. IFN-gamma is associated with protection against PerF, which depends more on egg load and egg-associated toxicity.
The Multiple Roles of Educators in Children's Creativity

ion is a procedure that helps people to avoid those kinds of traps to see new solutions. But, it does not just say “throw out everything you know. ” Instead, it encourages people to use their knowledge, but to represent their problems and access their knowledge at a very general level of abstraction. In fact, research from my own laboratory shows that when people are encouraged to take abstract approaches
Intermediate CAG Repeat Expansion in the ATXN2 Gene Is a Unique Genetic Risk Factor for ALS−A Systematic Review and Meta-Analysis of Observational Studies

Amyotrophic lateral sclerosis (ALS) is a rare degenerative condition of the motor neurons. Over 10% of ALS cases are linked to monogenic mutations, with the remainder thought to be due to other risk factors, including environmental factors, genetic polymorphisms, and possibly gene-environmental interactions. We examined the association between ALS and an intermediate CAG repeat expansion in the ATXN2 gene using a meta-analytic approach. Observational studies were searched with relevant disease and gene terms from MEDLINE, EMBASE, and PsycINFO from January 2010 through to January 2014. All identified articles were screened using disease terms, gene terms, population information, and CAG repeat information according to PRISMA guidelines. The final list of 17 articles was further evaluated based on the study location, time period, and authors to exclude multiple usage of the same study populations: 13 relevant articles were retained for this study. The range 30–33 CAG repeats in the ATXN2 gene was most strongly associated with ALS. The meta-analysis revealed that the presence of an intermediate CAG repeat (30-33) in the ATXN2 gene was associated with an increased risk of ALS [odds ratio (OR) = 4.44, 95%CI: 2.91–6.76)] in Caucasian ALS patients. There was no significant difference in the association of this CAG intermediate repeat expansion in the ATXN2 gene between familial ALS cases (OR = 3.59, 1.58–8.17) and sporadic ALS cases (OR = 3.16, 1.88–5.32). These results indicate that the presence of intermediate CAG repeat expansion in the ATXN2 gene is a specific genetic risk factor for ALS, unlike monogenic mutations with an autosomal dominant transmission mode, which cause a more severe phenotype of ALS, with a higher prevalence in familial ALS.