Miracle-dz/UniFAR-FTUs huggingface dataset:
Successful TRPV1 antagonist treatment for cardiac hypertrophy and heart failure in mice

Heart failure is becoming a global epidemic. It exerts a staggering toll on quality of life, and substantial medical and economic impact. In a pre-clinical model of cardiac hypertrophy and heart failure, we were able to overcome loss of heart function by administering the TRPV1 antagonist BCTC (4-(3-Chloro-2-pyridinyl)-N-[4-(1,1-dimethylethyl)phenyl]-1-piperazinecarboxamide). The results presented here identify TRPV1 antagonists as new treatment options for cardiac hypertrophy and heart failure.
InP-based ultra-fast photodetectors for millimeter-wave sub-harmonic mixers

A novel scheme for efficient optoelectronic down-conversion of millimeter-wave signals is presented. A Coplanar Waveguide-integrated Uni-Traveling Carrier Photodiode with a Traveling wave design was used as the optoelectronic mixer. For fundamental mixing at a frequency of 100 GHz a conversion gain of −32 dB was found that is a significant improvement compared to previously published results. For sub-harmonically pumped mixing lower gain was measured depending on the harmonic order. Flat IF response was found for a wide range of frequencies.
Parenting practices as mediating variables between parents' psychopathology and oppositional defiant disorder in preschoolers.

BACKGROUND Oppositional defiant disorder (ODD) is very frequent in preschoolers. The severity and the long-term negative outcomes make the understanding of this disorder a priority. The goal in this study was to assess the mediating role of parenting practices in the relationship between parents' psychopathology and ODD in preschoolers. METHOD A community sample of 622 children was assessed longitudinally at age 3 and age 5. Parents reported on children's psychopathology through a diagnostic interview, and on their own psychological state and parenting style through questionnaires. RESULTS At ages 3 and 5, corporal punishment mediated the relationships between mothers' anxiety-depression and ODD (in girls), between mothers' aggressive behavior and ODD (in boys), and between parents' rule-breaking and ODD both in boys and girls. For both sexes, there was a direct association between mothers' aggressive behavior score and ODD. The association between fathers' psychopathology and ODD was not mediated by the fathers' parenting practices. Fathers' anxiety-depression and aggressive behavior scores were directly associated with ODD. CONCLUSIONS Parents' psychopathology must be explored and, in families where such psychopathology is a relevant variable, parenting practices must be addressed with a view to the prevention and treatment of children's ODD in the preschool years.
Cyclin B1–Cdk1 Activation Continues after Centrosome Separation to Control Mitotic Progression

Activation of cyclin B1–cyclin-dependent kinase 1 (Cdk1), triggered by a positive feedback loop at the end of G2, is the key event that initiates mitotic entry. In metaphase, anaphase-promoting complex/cyclosome–dependent destruction of cyclin B1 inactivates Cdk1 again, allowing mitotic exit and cell division. Several models describe Cdk1 activation kinetics in mitosis, but experimental data on how the activation proceeds in mitotic cells have largely been lacking. We use a novel approach to determine the temporal development of cyclin B1–Cdk1 activity in single cells. By quantifying both dephosphorylation of Cdk1 and phosphorylation of the Cdk1 target anaphase-promoting complex/cyclosome 3, we disclose how cyclin B1–Cdk1 continues to be activated after centrosome separation. Importantly, we discovered that cytoplasmic cyclin B1–Cdk1 activity can be maintained even when cyclin B1 translocates to the nucleus in prophase. These experimental data are fitted into a model describing cyclin B1–Cdk1 activation in human cells, revealing a striking resemblance to a bistable circuit. In line with the observed kinetics, cyclin B1–Cdk1 levels required to enter mitosis are lower than the amount of cyclin B1–Cdk1 needed for mitotic progression. We propose that gradually increasing cyclin B1–Cdk1 activity after centrosome separation is critical to coordinate mitotic progression.
Crystal structure of Manduca sexta prophenoloxidase provides insights into the mechanism of type 3 copper enzymes

Arthropod phenoloxidase (PO) generates quinones and other toxic compounds to sequester and kill pathogens during innate immune responses. It is also involved in wound healing and other physiological processes. Insect PO is activated from its inactive precursor, prophenoloxidase (PPO), by specific proteolysis via a serine protease cascade. Here, we report the crystal structure of PPO from a lepidopteran insect at a resolution of 1.97 Å, which is the initial structure for a PPO from the type 3 copper protein family. Manduca sexta PPO is a heterodimer consisting of 2 homologous polypeptide chains, PPO1 and PPO2. The active site of each subunit contains a canonical type 3 di-nuclear copper center, with each copper ion coordinated with 3 structurally conserved histidines. The acidic residue Glu-395 located at the active site of PPO2 may serve as a general base for deprotonation of monophenolic substrates, which is key to the ortho-hydroxylase activity of PO. The structure provides unique insights into the mechanism by which type 3 copper proteins differ in their enzymatic activities, albeit sharing a common active center. A drastic change in electrostatic surface induced on cleavage at Arg-51 allows us to propose a model for localized PPO activation in insects.
Feasibility of the music therapy assessment tool for awareness in disorders of consciousness (MATADOC) for use with pediatric populations

Measuring responsiveness to gain accurate diagnosis in populations with disorders of consciousness (DOC) is of central concern because these patients have such complex clinical presentations. Due to the uncertainty of accuracy for both behavioral and neurophysiological measures in DOC, combined assessment approaches are recommended. A number of standardized behavioral measures can be used with adults with DOC with minor to moderate reservations relating to the measures’ psychometric properties and clinical applicability. However, no measures have been standardized for use with pediatric DOC populations. When adapting adult measures for children, confounding factors include developmental considerations for language-based items included in all DOC measures. Given the lack of pediatric DOC measures, there is a pressing need for measures that are sensitive to the complex clinical presentations typical of DOC and that can accommodate the developmental levels of pediatric populations. The music therapy assessment tool for awareness in disorders of consciousness (MATADOC) is a music-based measure that has been standardized for adults with DOC. Given its emphasis on non-language based sensory stimuli, it is well-suited to pediatric populations spanning developmental stages. In a pre-pilot exploratory study, we examined the clinical utility of this measure and explored trends for test-retest and inter-rater agreement as well as its performance against external reference standards. In several cases, MATADOC items in the visual and auditory domains produced outcomes suggestive of higher level functioning when compared to outcomes provided by other DOC measures. Preliminary findings suggest that the MATADOC provides a useful protocol and measure for behavioral assessment and clinical treatment planning with pediatric DOC. Further research with a larger sample is warranted to test a version of the MATADOC that is refined to meet developmental needs of pediatric DOC populations.
Cardiac Signals Are Independently Associated with Temporal Discounting and Time Perception

Cardiac signals reflect the function of the autonomic nervous system (ANS) and have previously been associated with a range of self-regulatory behaviors such as emotion regulation and memory recall. It is unknown whether cardiac signals may also be associated with self-regulation in the temporal domain, in particular impulsivity. We assessed both decision impulsivity (temporal discounting, TD) and time perception impulsivity (duration reproduction, DR) in 120 participants while they underwent electrocardiography in order to test whether cardiac signals were related to these two aspects of impulsivity. We found that over the entire period of task performance, individuals with higher heart rates had a tendency toward lower discount rates, supporting previous research that has associated sympathetic responses with decreased impulsivity. We also found that low-frequency components of heart rate variability (HRV) were associated with a less accurate perception of time, suggesting that time perception may be modulated by ANS function. Overall, these findings constitute preliminary evidence that autonomic function plays an important role in both decision impulsivity and time perception.
Modeling auxiliary information in Bayesian network based ASR

Automatic speech recognition bases its models on the acoustic features derived from the speech signal. Some have investigated replacing or supplementing these features with information that can not be precisely measured (articulator positions, pitch, gender, etc.) automatically. Consequently, automatic estimations of the desired information would be generated. This data can degrade performance due to its imprecisions. In this paper, we describe a system that treats pitch as an auxiliary information within the framework of Bayesian networks, resulting in improved performance.
Birds and people in Europe

At a regional scale, species richness and human population size are frequently positively correlated across space. Such patterns may arise because both species richness and human density increase with energy availability. If the species–energy relationship is generated through the ‘more individual’ hypothesis, then the prediction is that areas with high human densities will also support greater numbers of individuals from other taxa. We use the unique data available for the breeding birds in Europe to test this prediction. Overall regional densities of bird species are higher in areas with more people; species of conservation concern exhibit the same pattern. Avian density also increases faster with human density than does avian biomass, indicating that areas with a higher human density have a higher proportion of small–bodied individuals. The analyses also underline the low numbers of breeding birds in Europe relative to humans, with a median of just three individual birds per person, and 4 g of bird for every kilogram of human.
Prolonged infancy and attachment security: Comparative case analysis of children with intellectual disability from India

People with intellectual disability possess poor relationship skills and lack attachment relationships. Research has shown that this low relationship building ability is evident right from birth in the interactions with the mother. The present study addresses these two arguments through case study method. 11 children with intellectual disability from a special school at Mangalore, South India were the participants. With the purpose of developing close relationship, the researcher interacted with the participants for an academic year (10 months). The interactions resulted in close relationships for both. Interviews were conducted with mothers, and other significant people to find out the relationship histories. The analyses of the data revealed that children with intellectual disability are able to develop attachment relationship. The prolonged infancy of children with intellectual disability from developmental delays provides more space for infantmother interaction. The relationship orientation and the inheritance right in Indian culture fostered the attachment relationship during prolonged infancy stage for the participants under study. The relationship building ability of children with intellectual disability is as par as any other normal developing individual, provided with an opportunity for sensitive interaction.
The Effects of Spatiotemporal Changes in Land Degradation on Ecosystem Services Values in Sanjiang Plain, China

Sanjiang Plain has undergone dramatic land degradation since the 1950s, which has caused negative effects on ecosystems services and sustainability. In this study, we used trajectory analysis as well as the Lorenz curve, Gini coefficient and relative land use suitability index (R) to analyze spatiotemporal changes of land degradation from 1954 to 2013 and to make a preliminary estimation of the role of human activities in observed environmental changes using a five-stage LULC data. This study also explored the effect of land degradation on the values and structure of ecosystem services. Our results indicated that more than 70% of marsh area originally present in the study area has been lost, whereas less than 30% was preserved. Dry farmland and paddy increased rapidly at the expense of marsh, forest and grassland. Land use structure became more unsuitable during the past 60 years. Compared with natural factors, human activities played a dominant role (89.67%) in these changes. This dramatic land degradation caused the significant loss of ecosystem services values and the changes in the structure of ecosystem services. These results confirmed the effectiveness of combining temporal trajectory analysis, the Lorenz curve/Gini coefficient and the R index in analyzing spatiotemporal changes in progressive land degradation. Also, these findings highlight the necessity of separating dry farmland from paddy when studying land degradation changes and the effects on ecosystem services in regions where dry farmland has often been converted to paddy.
Perioperative analgesia after intrathecal fentanyl and morphine or morphine alone for cesarean section

Objectives: Intrathecal morphine is used in the postoperative management of pain after caesarean section (CS), but might not be optimal for intraoperative analgesia. We hypothesized that intrathecal fentanyl could supplement intraoperative analgesia when added to a local anesthetic and morphine without affecting management of postoperative pain. Methods: This prospective, randomized, double-blind, parallel-group study included 60 parturients scheduled for elective CS. Spinal anesthesia consisted of bupivacaine with either morphine 100 &mgr;g (M group), or fentanyl 25 &mgr;g and morphine 100 &mgr;g (FM group). The frequency of intraoperative pain and pethidine consumption in the 24 hours postoperatively was recorded. Results: Fewer patients in the FM group required additional intraoperative analgesia (P < .01, relative risk 0.06, 95% confidence interval [CI] 0.004–1.04). The FM group was noninferior to the M group for 24-hour opioid consumption (95% CI −10.0 mg to 45.7 mg, which was below the prespecified boundary of 50 mg). Pethidine consumption in postoperative hours 1 to 12 was significantly higher in the FM group (P = .02). Postoperative nausea and vomiting (PONV) were more common in the FM group (P = .01). Visual analog scale scores, effective analgesia, Apgar scores, and rates of pruritus and respiratory depression were similar between the groups. Conclusions: Intrathecal combination of fentanyl and morphine may provide better perioperative analgesia than morphine alone in CS and could be useful when the time from anesthesia to skin incision is short. However, an increase in PONV and possible acute spinal opioid tolerance after addition of intrathecal fentanyl warrants further investigation using lower doses of fentanyl.
The emerging science of precision medicine and pharmacogenomics for Parkinson's disease

Current therapies for Parkinson's disease are problematic because they are symptomatic and have adverse effects. New drugs have failed in clinical trials because of inadequate efficacy. At the core of the problem is trying to make one drug work for all Parkinson's disease patients, when we know this premise is wrong because (1) Parkinson's disease is not a single disease, and (2) no two individuals have the same biological makeup. Precision medicine is the goal to strive for, but we are only at the beginning stages of building the infrastructure for one of the most complex projects in the history of science, and it will be a long time before Parkinson's disease reaps the benefits. Pharmacogenomics, a cornerstone of precision medicine, has already proven successful for many conditions and could also propel drug discovery and improve treatment for Parkinson's disease. To make progress in the pharmacogenomics of Parkinson's disease, we need to change course from small inconclusive candidate gene studies to large‐scale rigorously planned genome‐wide studies that capture the nuclear genome and the microbiome. Pharmacogenomic studies must use homogenous subtypes of Parkinson's disease or apply the brute force of statistical power to overcome heterogeneity, which will require large sample sizes achievable only via internet‐based methods and electronic databases. Large‐scale pharmacogenomic studies, together with biomarker discovery efforts, will yield the knowledge necessary to design clinical trials with precision to alleviate confounding by disease heterogeneity and interindividual variability in drug response, two of the major impediments to successful drug discovery and effective treatment. © 2017 International Parkinson and Movement Disorder Society
Efficacy of local treatment with chlorhexidine gluconate drugs on the clinical status of periodontium in chronic periodontitis patients.

PURPOSE Chlorhexidine gluconate is a relatively commonly used chemotherapeutic in the treatment of periodontitis (P), exhibiting antimicrobial capabilities against Gram-negative and Gram-positive bacteria, and fungi. This compound is a component of various preparations for topical use in the form of solutions for mouthrinsing or peri-irrigation, gels, varnishes, chips and even chewing gums. The aim of the study was the clinical evaluation of periodontium after treatment with one of the drugs containing chlorhexidine gluconate (Corsodyl) as compared to professional tooth cleaning in patients with chronic periodontitis. MATERAL AND METHODS: Forty subjects enrolled in the study were divided into four groups, 10 in each group, according to the mode of treatment (Corsodyl rinse, Corsodyl gel, Corsodyl gel + surgical dressing, scaling). RESULTS The greatest differences between baseline and follow-up examinations were observed in the group where surgical dressing was applied in addition to Corsodyl gel and in the group treated with scaling. CONCLUSIONS Chlorhexidine gluconate should be more frequently used as a drug adjunct to classic periodontal therapy, especially in the forms allowing its direct application to the periodontal pockets.
Language-driven system design

Studies have shown significant benefits of the use of domain-specific languages. However, designing a DSL still seems to be an art, rather than a craft, following a clear methodology. In this paper we discuss a first step towards a methodology for designing such languages. The presented approach, which is referred to as the language-driven approach, is rooted informal techniques and independent of accepted software engineering process models. We illustrate the approach with a small and instructive case study.
MRI shows increased sciatic nerve cross sectional area in inherited and inflammatory neuropathies

Measurements of the cross sectional area of the sciatic nerve are described in a group of 10 patients with genetically confirmed Charcot–Marie–Tooth disease type 1A (CMT1A), nine patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 10 healthy controls using MRI. One mid-thigh of each individual was imaged using a short tau inversion recovery sequence and the nerve appearance evaluated radiologically with respect to the signal intensity and visibility of the internal neural structure. The cross sectional area of the sciatic nerve of each individual was measured by defining irregular enclosing regions of interest on the MRI images. The sciatic nerve area was enlarged in both CMT1A (p<0.001) and CIDP (p=0.008) compared with controls and in CMT1A compared with CIDP (p<0.001). Median (interquartile range) areas were 67.6 (16.2) mm2 for the CIDP group, 135.9 (46.5) mm2 for the CMT1A group and 43.3 (19.9) mm2 for the control group. The critical upper value for discriminating pathologically enlarged nerves from normal controls with p<0.05 was 64.4 mm2. Quantification of sciatic nerve hypertrophy on MRI may be of assistance in cases where the diagnosis is still in doubt, providing an objective pathological marker complimenting other clinical investigations.
Attentional control adjustments in Eriksen and Stroop task performance can be independent of response conflict

In the Eriksen flanker and colour-word Stroop tasks, the response time (RT) difference between incongruent and congruent trials is smaller following incongruent trials than following congruent trials: the “Gratton effect” (Gratton, Coles, & Donchin, 1992). According to the prevailing conflict-monitoring theory (Botvinick, Braver, Barch, Carter, & Cohen, 2001), the Gratton effect reflects attentional control adjustment following response conflict on incongruent trials. However, because previous studies compared incongruent and congruent trials, it remains unclear to what extent the Gratton effect is driven by incongruent rather than congruent trials. To resolve this issue, we included neutral trials in addition to incongruent and congruent trials in the Eriksen (Experiment 1) and Stroop (Experiment 2) tasks. Participants responded manually and vocally in both tasks. Moreover, we assessed responding to Stroop stimuli that were preceded by neutral cues or by incongruent- or congruent-predicting cues (Experiment 3). In all three experiments, the RT difference between incongruent and congruent trials was larger for postcongruent trials than for postincongruent and postneutral trials. These findings suggest that control adjustments can be independent of response conflict, challenging conflict-monitoring theory.
Effects of Differential Genotyping Error Rate on the Type I Error Probability of Case-Control Studies

Objectives: It is well known that genotyping error adversely affects the power of genetic case-control association studies but there is little research on its effects on type I error, and none that has addressed possible differences in genotype error rates between cases and controls. Methods: We used simulations to examine the influence of genotyping error on the type I error probability given by case-control studies. The effect of genotyping error on the magnitude of type I error was explored for a single marker of varying minor allele frequency (MAF), and for haplotypic tests based on two markers with varying MAF and linkage disequilibrium (LD) measure r2. Results: We show that even with low genotyping error rates (<0.01), systematic differences in the error rate between samples can result in type I error rates substantially above 0.05. The effect was maximal for markers with small MAF, markers in strong LD, and where a common allele is more frequently misclassified as a rare allele than vice versa. The problem was also exacerbated by the use of large samples. Conclusions: Our results show that small differential genotyping error rates between cases and controls pose significant problems for association analyses. Differential genotyping error rates are particularly likely to arise where genotype data are combined from multiple sites, or where case genotypes are examined against archived reference population cohort genotypes that are being generated in several countries. Although these strategies may be necessary to obtain adequately powered samples, our data show the importance of stringent quality control. Furthermore, associations based on rare haplotypes should be treated with caution.