Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence From Human Myectomy Samples That MYBPC3 Mutations Cause Hypertrophic Cardiomyopathy Through Haploinsufficiency*

Rationale: Most sarcomere gene mutations that cause hypertrophic cardiomyopathy are missense alleles that encode dominant negative proteins. The potential exceptions are mutations in the MYBPC3 gene (encoding cardiac myosin-binding protein-C [MyBP-C]), which frequently encode truncated proteins. Objective: We sought to determine whether there was evidence of haploinsufficiency in hypertrophic cardiomyopathy caused by MYBPC3 mutations by comparing left ventricular muscle from patients undergoing surgical myectomy with samples from donor hearts. Methods and Results: MyBP-C protein and mRNA levels were quantitated using immunoblotting and RT-PCR. Nine of 37 myectomy samples had mutations in MYBPC3: 2 missense alleles (Glu258Lys, Arg502Trp) and 7 premature terminations. No specific truncated MyBP-C peptides were detected in whole muscle homogenates of hypertrophic cardiomyopathy tissue. However, the overall level of MyBP-C in myofibrils was significantly reduced (P<0.0005) in tissue containing either a truncation or missense MYBPC3 mutation: 0.76±0.03 compared with 1.00±0.05 in donor and 1.01±0.06 in non-MYBPC3 mutant myectomies. Conclusions: The absence of any detectable truncated MyBP-C argues against its incorporation in the myofiber and any dominant negative effect. In contrast, the lowered relative level of full length protein in both truncation and missense MYBPC3 mutations argues strongly that haploinsufficiency is sufficient to cause the disease.
Metaanalysis of filler materials in periapical surgery.

OBJECTIVE To evaluate the success and failure, apical sealing and biocompatibility of silver amalgam, IRM, SuperEBA and MTA as retrograde filler materials. STUDY DESIGN A metaanalysis is made of filler materials in periapical surgery, evaluating a total of 30 articles published in recent years. RESULTS Percentage success with silver amalgam was 76.5% and slightly inferior to that afforded by IRM. Performance in turn increased considerably when the materials used were SuperEBA or MTA. As regards marginal leakage, MTA with a mean leakage time of 65.5 days afforded the best results, followed by SuperEBA, IRM and silver amalgam. MTA was the most biocompatible of the materials studied, with practically no inflammatory response, while inflammation proved mild or moderate with SuperEBA, mild with IRM, and moderate to severe in the case of silver amalgam. Tissue regeneration was only observed with MTA, in the same way as cement appositioning. Bone neoformation was observed with all four filler materials. CONCLUSIONS MTA appears to be an ideal material, though the results obtained require confirmation by in vivo studies.
Exploring sequences of speech and laughter activity using visualisations of conversations

In this study, we analysed laughter in dyadic conversational interaction. We attempted to categorise patterns of speaking and laughing activity in conversation in order to gain more insight into how speaking and laughing are timed and related to each other. Special attention was paid to a particular sequencing of speech and laughter activity that is intended to invite an interlocutor to laugh (i.e. ‘invitation-acceptance’ scheme): the speaker invites the listener to laugh by producing a laugh after his/her own utterance, indicating that it is appropriate to laugh. We explored these kinds of sequences through visualisations of speech and laughter activity in conversations. Based on manual transcriptions of the HCRC Map Task corpus, we generated visualisations of speech and laughter activity. Using these visualisations, we found that people indeed show a tendency to adhere to the ‘invitation-acceptance’ scheme and that people tend to ‘wait’ to be invited to a shared laughter event rather than to ‘anticipate’ it. These speech-and-laugh-activity plots have shown to be helpful in analysing the interplay between laughing and speaking in conversation and can be used as a tool to enhance the researcher’s intuition on underresearched fields.
MISSING FEATURE THEORY IN ASR: MAKE SURE YOU MISS THE RIGHT TYPE OF FEATURES

In this paper we investigate acoustic backing-off as an opera­ tionalization of Missing Feature Theory to increase recognition robustness in adverse acoustic conditions. Acoustic backing-off effectively removes the detrimental influence of outlier values from the local decisions in the Viterbi algorithm. It does so without prior knowledge about the specific feature vector ele­ ments which are unreliable; thus, the technique avoids the need for explicit outlier detection. From the theory underlying Mis­ sing Feature Theory it appears that acoustic feature representa­ tions which smear local spectro-temporal distortions over all fea­ ture vector elements are inherently unsuitable. Our experiments in the context of connected digit recognition over the telephone are presented that confirm this prediction. Our results show that feature representations which minimize distortion smearing are most suited to be used in combination with Missing Feature The­ ory. Using additive band limited noise as a distortion, we found that acoustic backing-off can achieve a word error rate reduction of when within vector filtered mel-frequency log-energy co­ efficients are used.
Factors associated with the occurrence of claw disorders in dairy cows under smallholder production systems in urban and peri-urban areas of Nairobi, Kenya

A cross-sectional study was carried out between December 2005 and June 2006 in smallholder dairy farms within and around Nairobi, Kenya to determine risk factors associated with the occurrence of claw disorders in dairy cows. Farm-and cow-level factors were evaluated in 32 farms and 300 cows respectively. The occurrence of claw disorders was determined. Chronic laminitis was significantly (P<0.05) associated with three or higher parities (χ 2 = 11.57, P = 0.009), lactation period between 90 to 180 days (χ 2 = 9.75, P = 0.021), overstocking (O.R. = 1.7, χ 2 = 24.29, P = 0.0002), absence of cubicle bedding (O.R. = 1.6, χ 2 = 29.13, P = 0.003), earthen floor (O.R. = 1.5, χ 2 = 8.98, P = 0.0006) and a curb dividing walk-alleys and cubicles (O.R. = 1.5, χ 2 = 5.06, P = 0.0262). Subclinical laminitis was significantly (P<0.05) associated with lactation period between 1-90 days (χ2 = 9.06, P = 0.028), and concentrate feeding (O.R. = 2.08, χ2 = 5.5, P = 0.0212). However, lack of mineral supplementation and leaving manure (slurry) in the walk alleys for a long time seemed to enhance laminitis. Concentrate feeding had positive (contributor) (β-estimate = 2.187, P<0.05) association with sole bruising, while mineral supplementation (β-estimate = -4.59, P<0.05) and earthen floor (β-estimate = -1.796, P<0.05) had negative (protector) association. White line separation was enhanced by concentrate feeding (β-estimate = 3.69, P = 0.002), but reduced by mineral supplementation (β-estimate = -4.07, P<0.05), and frequent manure (slurry) removal from walk-alleys (β-estimate = -3.58, P<0.05). Non-slip and non-defective concrete floors were negatively (protectively) (β-estimate = -1.969, P<0.05) associated with heel erosion.
Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye

Significance Retinal vascular diseases are a leading cause of blindness. Optical coherence tomography (OCT) has become the standard imaging modality for evaluating fluid accumulation in these diseases and for guiding treatment. However, fluorescein angiography (FA) is still required for initial evaluation of retinal ischemia and choroidal neovascularization, which are not visible in conventional structural OCT. The limitations of FA include poor penetration of fluorescence through blood and pigment, inability to determine the depth of the pathology due to its two-dimensional nature, and some uncommon but potentially severe complications. As a noninvasive three-dimensional alternative, OCT angiography may be used in routine screening and monitoring to provide new information for clinical diagnosis and management. Retinal vascular diseases are important causes of vision loss. A detailed evaluation of the vascular abnormalities facilitates diagnosis and treatment in these diseases. Optical coherence tomography (OCT) angiography using the highly efficient split-spectrum amplitude decorrelation angiography algorithm offers an alternative to conventional dye-based retinal angiography. OCT angiography has several advantages, including 3D visualization of retinal and choroidal circulations (including the choriocapillaris) and avoidance of dye injection-related complications. Results from six illustrative cases are reported. In diabetic retinopathy, OCT angiography can detect neovascularization and quantify ischemia. In age-related macular degeneration, choroidal neovascularization can be observed without the obscuration of details caused by dye leakage in conventional angiography. Choriocapillaris dysfunction can be detected in the nonneovascular form of the disease, furthering our understanding of pathogenesis. In choroideremia, OCT's ability to show choroidal and retinal vascular dysfunction separately may be valuable in predicting progression and assessing treatment response. OCT angiography shows promise as a noninvasive alternative to dye-based angiography for highly detailed, in vivo, 3D, quantitative evaluation of retinal vascular abnormalities.
An educational tool for basic techniques in beginner's pencil drawing

A picture is one of important research subjects in order to make our life spiritually rich. Most studies on pictures, however, only propose some substitute functions of actual drawing or painting materials. There is no system that evaluates pictures drawn by users and gives advice about them. We propose a learning support system for basic techniques in beginner's pencil drawing. The proposed system receives a subject (motif) data set and an image of user's sketch and returns advice to the user. The system is composed of the four subsystems: feature extraction of motifs, feature extraction of sketches, error identification, and generation and presentation of advice. We developed and experimented a prototype system limited to treat a basic motif and some principal advice. As a result, the validity of the proposed system was confirmed.
Estimating Causal Effects With Matching Methods in the Presence and Absence of Bias Cancellation

This article explores the implications of bias cancellation on the estimate of average treatment effects using ordinary least squares (OLS) and Rubin-style matching methods. Bias cancellation (offsetting biases at high and low propensities for treatment in estimates of treatment effects that are uncorrected for nonrandom selection) has been observed when job training is the treatment variable and earnings is the outcome variable. Contrary to published assertions in the literature, bias cancellation is not explainable in terms of the standard selection model, which assumes a symmetric distribution for the errors in the structural and assignment equations. A substantive rationale for bias cancellation is offered, which conceptualizes bias cancellation as the result of a mixture process based on two distinct individual-level decision-making models. While the general properties are unknown, the existence of bias cancellation appears to reduce the average bias in both OLS and matching methods relative to the symmetric distribution case.
Interaction between Dysfunctional Connectivity at Rest and Heroin Cues-Induced Brain Responses in Male Abstinent Heroin-Dependent Individuals

Background The majority of previous heroin cue-reactivity functional magnetic resonance imaging (fMRI) studies focused on local function impairments, such as inhibitory control, decision-making and stress regulation. Our previous studies have demonstrated that these brain circuits also presented dysfunctional connectivity during the resting state. Yet few studies considered the relevance of resting state dysfunctional connectivity to task-related neural activity in the same chronic heroin user (CHU). Methodology/Principal Findings We employed the method of graph theory analysis, which detected the abnormality of brain regions and dysregulation of brain connections at rest between 16 male abstinent chronic heroin users (CHUs) and 16 non-drug users (NDUs). Using a cue-reactivity task, we assessed the relationship between drug-related cue-induced craving activity and the abnormal topological properties of the CHUs' resting networks. Comparing NDUs' brain activity to that of CHUs, the intensity of functional connectivity of the medial frontal gyrus (meFG) in patients' resting state networks was prominently greater and positively correlated with the same region's neural activity in the heroin-related task; decreased functional connectivity intensity of the anterior cingulate cortex (ACC) in CHUs at rest was associated with more drug-related cue-induced craving activities. Conclusions These results may indicate that there exist two brain systems interacting simultaneously in the heroin-addicted brain with regards to a cue-reactivity task. The current study may shed further light on the neural architecture that supports craving responses in heroin dependence.
Cerebrospinal Fluid Levels of Amyloid Beta 1-43 Mirror 1-42 in Relation to Imaging Biomarkers of Alzheimer’s Disease

Introduction: Amyloid beta 1-43 (Aβ43), with its additional C-terminal threonine residue, is hypothesized to play a role in early Alzheimer’s disease pathology possibly different from that of amyloid beta 1-42 (Aβ42). Cerebrospinal fluid (CSF) Aβ43 has been suggested as a potential novel biomarker for predicting conversion from mild cognitive impairment (MCI) to dementia in Alzheimer’s disease. However, the relationship between CSF Aβ43 and established imaging biomarkers of Alzheimer’s disease has never been assessed. Materials and Methods: In this observational study, CSF Aβ43 was measured with ELISA in 89 subjects; 34 with subjective cognitive decline (SCD), 51 with MCI, and four with resolution of previous cognitive complaints. All subjects underwent structural MRI; 40 subjects on a 3T and 50 on a 1.5T scanner. Forty subjects, including 24 with SCD and 12 with MCI, underwent 18F-Flutemetamol PET. Seventy-eight subjects were assessed with 18F-fluorodeoxyglucose PET (21 SCD/7 MCI and 11 SCD/39 MCI on two different scanners). Ten subjects with SCD and 39 with MCI also underwent diffusion tensor imaging. Results: Cerebrospinal fluid Aβ43 was both alone and together with p-tau a significant predictor of the distinction between SCD and MCI. There was a marked difference in CSF Aβ43 between subjects with 18F-Flutemetamol PET scans visually interpreted as negative (37 pg/ml, n = 27) and positive (15 pg/ml, n = 9), p < 0.001. Both CSF Aβ43 and Aβ42 were negatively correlated with standardized uptake value ratios for all analyzed regions; CSF Aβ43 average rho -0.73, Aβ42 -0.74. Both CSF Aβ peptides correlated significantly with hippocampal volume, inferior parietal and frontal cortical thickness and axial diffusivity in the corticospinal tract. There was a trend toward CSF Aβ42 being better correlated with cortical glucose metabolism. None of the studied correlations between CSF Aβ43/42 and imaging biomarkers were significantly different for the two Aβ peptides when controlling for multiple testing. Conclusion: Cerebrospinal fluid Aβ43 appears to be strongly correlated with cerebral amyloid deposits in the same way as Aβ42, even in non-demented patients with only subjective cognitive complaints. Regarding imaging biomarkers, there is no evidence from the present study that CSF Aβ43 performs better than the classical CSF biomarker Aβ42 for distinguishing SCD and MCI.
A stochastic MILP model for long-term hydrothermal scheduling considering water resource management

A multistage scenario tree based stochastic model is proposed for long-term hydrothermal scheduling (LHTS) in this paper to hedge against the uncertainties of natural inflows, water demand, grid load and wind power generation. With scenarios reduction, a 3-stage, 81-scenario stochastic tree is established based on stochastic weather condition and net load. In addition, detailed formulations of hydrothermal system and water resource management such as water supply/recession procedure, distributed water usage allocation policy and etc. are also included in the basic nonlinear model. Then the nonlinear functions in the formulation such as thermal generating costs function, hydro power production function, water recession function and reservoir evaporation function are replaced by their piecewise linear equivalents and the stochastic mixed integer linear programming (MILP) formulation is solved by commercial solver CPLEX. The numerical results show that the proposed stochastic MILP model for LHTS is efficient.
Bifurcation in electrostatic resistive drift wave turbulence

The Hasegawa-Wakatani equations, coupling plasma density, and electrostatic potential through an approximation to the physics of parallel electron motions, are a simple model that describes resistive drift wave turbulence. Numerical analyses of bifurcation phenomena in the model are presented, that provide new insights into the interactions between turbulence and zonal flows in the tokamak plasma edge region. The simulation results show a regime where, after an initial transient, drift wave turbulence is suppressed through zonal flow generation. As a parameter controlling the strength of the turbulence is tuned, this zonal-flow-dominated state is rapidly destroyed and a turbulence-dominated state re-emerges. The transition is explained in terms of the Kelvin-Helmholtz stability of zonal flows. This is the first observation of an upshift of turbulence onset in the resistive drift wave system, which is analogous to the well-known Dimits shift in turbulence driven by ion temperature gradients.
Identity and the Economics of Organizations

The economics of organizations is replete with the pitfalls of monetary rewards and punishments to motivate workers. If economic incentives do not work, what does? This paper proposes that workers' self-image as jobholders, coupled with their ideal as to how their job should be done, can be a major work incentive. It shows how such identities can flatten reward schedules, as they solve "principal-agent" problem. The paper also identifies and explores a new tradeoff: supervisors may provide information to principals, but create rifts within the workforce and reduce employees' intrinsic work incentives. We motivate the theory with examples from the classic sociology of military and civilian organizations.
Circulating microRNAs as Potential Biomarkers of Infectious Disease

microRNAs (miRNAs) are a class of small non-coding endogenous RNA molecules that regulate a wide range of biological processes by post-transcriptionally regulating gene expression. Thousands of these molecules have been discovered to date, and multiple miRNAs have been shown to coordinately fine-tune cellular processes key to organismal development, homeostasis, neurobiology, immunobiology, and control of infection. The fundamental regulatory role of miRNAs in a variety of biological processes suggests that differential expression of these transcripts may be exploited as a novel source of molecular biomarkers for many different disease pathologies or abnormalities. This has been emphasized by the recent discovery of remarkably stable miRNAs in mammalian biofluids, which may originate from intracellular processes elsewhere in the body. The potential of circulating miRNAs as biomarkers of disease has mainly been demonstrated for various types of cancer. More recently, however, attention has focused on the use of circulating miRNAs as diagnostic/prognostic biomarkers of infectious disease; for example, human tuberculosis caused by infection with Mycobacterium tuberculosis, sepsis caused by multiple infectious agents, and viral hepatitis. Here, we review these developments and discuss prospects and challenges for translating circulating miRNA into novel diagnostics for infectious disease.
Distribution and Determinants of Plasma Homocysteine Levels in Rural Chinese Twins across the Lifespan

Plasma homocysteine (Hcy) is a modifiable, independent risk factor for cardiovascular disease (CVD) and is affected by both environmental and genetic factors. This study aimed to describe the gender- and age-specific distribution of Hcy concentration for 1117 subjects aged 10–66 years, a subset of a community-based rural Chinese twin cohort. In addition, we examined environmental and genetic contributions to variances in Hcy concentration by gender and age groups. We found that the distribution pattern for Hcy varied by both age and gender. Males had higher Hcy than females across all ages. Elevated Hcy was found in 43% of male adults and 13% of female adults. Moreover, nearly one fifth of children had elevated Hcy. Genetic factors could explain 52%, 36% and 69% of the variation in Hcy concentration among children, male adults and female adults, respectively. The MTHFR C677T variant was significantly associated with Hcy concentrations. Smokers with the TT genotype had the highest Hcy levels. Overall, our results indicate that elevated Hcy is prevalent in the children and adults in this rural Chinese population. The early identification of elevated Hcy will offer a window of opportunity for the primary prevention of CVD and metabolic syndrome.
Serum levels of vascular endothelial growth factor in non-alcoholic fatty liver disease

Background This study aimed to assess the significance of serum levels of vascular endothelial growth factor (VEGF) in non-alcoholic fatty liver disease (NAFLD). Methods Sixty-seven consecutive NAFLD patients and 47 healthy controls who visited our liver clinics between May 2008 and December 2010 were included. The NAFLD diagnosis required elevated alanine aminotransferase and/or gamma-glutamyl transpeptidase levels, evidence of hepatic steatosis on ultrasound and/or liver histology, and exclusion of other causes of liver injury. Serum VEGF levels were determined by an enzyme immunoassay. Liver biopsy was obtained in 34 NAFLD patients. Histological lesions were scored by a liver histopathologist. Results Serum VEGF levels tended to be lower in matched NAFLD patients than in healthy controls (296±146 vs. 365±186 pg/mL, P=0.092); levels in patients with non-alcoholic steatohepatitis (NASH) also tended to be lower than in those with simple fatty liver (FL) (279±149 vs. 359±190 pg/mL, P=0.095); while VEGF levels were significantly lower in NASH patients than in healthy controls (279±149 vs. 365±186 pg/mL, P=0.041). VEGF levels offered poor predictability for the differentiation between NAFLD patients and controls or between NASH and FL patients. However, patients with high VEGF levels (≥300 pg/mL) were significantly more likely to have FL, either in the total NAFLD population (67% vs. 35%, P=0.019) or in the 34 NAFLD patients with liver biopsy (57% vs. 15%, P=0.023), while those with high VEGF levels also had a significantly lower mean fibrosis score (0.7±0.9 vs. 1.6±1.0, P=0.017). Conclusion Our data suggest that serum VEGF levels are equally high in healthy controls and in patients with simple fatty liver, but tend to decrease when NASH develops.