Miracle-dz/UniFAR-FTUs huggingface dataset:
Divergent effects of adrenaline in human induced pluripotent stem cell-derived cardiomyocytes obtained from hypertrophic cardiomyopathy

ABSTRACT Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease that affects the heart muscle with diverse clinical outcomes. HCM can cause sudden cardiac death (SCD) during or immediately after mild to rigorous physical activity in young patients. However, the mechanism causing SCD as a result of exercise remains unknown, but exercise-induced ventricular arrhythmias are thought to be responsible for this fatal consequence. To understand the disease mechanism behind HCM in a better way, we generated patient-specific induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from HCM patients carrying either the MYBPC3-Gln1061X or TPM1-Asp175Asn mutation. We extensively investigated the effects of low to high concentrations of adrenaline on action potential characteristics, and the occurrence of arrhythmias in the presence of various concentrations of adrenaline and in wash-out condition. We classified and quantified different types of arrhythmias observed in hiPSC-CMs, and found that the occurrence of arrhythmias was dependent on concentrations of adrenaline and positions of mutations in genes causing HCM. In addition, we observed ventricular tachycardia types of arrhythmias in hiPSC-CMs carrying the TPM1-Asp175Asn mutation. We additionally examined the antiarrhythmic potency of bisoprolol in HCM-specific hiPSC-CMs. However, bisoprolol could not reduce the occurrence of arrhythmias during administration or during the wash-out condition of adrenaline in HCM-specific hiPSC-CMs. Our study demonstrates hiPSC-CMs as a promising tool for studying HCM. The experimental design used in this study could be suitable and beneficial for studying other components and drugs related to cardiac disease in general. Summary: Different concentrations of adrenaline have divergent effects during and immediately after administration in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) obtained from hypertrophic cardiomyopathy (HCM) patients. Bisoprolol could not reduce the arrhythmias in HCM-specific hiPSC-CMs.
The Vitamin D Status of Prison Inmates

Introduction There is no comprehensive, systematic analysis of the vitamin D status of prisoners in the scientific literature. Objective To investigate the vitamin D status and its determinants in US prison inmates. Hypothesis Given the uniformity of dietary intake amongst inmates, vitamin D status will be determined by non-dietary factors such as skin pigmentation, security level-, and the duration of incarceration. Subjects and Methods A retrospective study of 526 inmates (males, n = 502, age 48.6±12.5 years; females, n = 24, age 44.1±12.2) in Massachusetts prisons. Vitamin D sufficiency, insufficiency, and deficiency were respectively defined as a 25(OH)D concentration 75 nmol/L; 50 to 75 nmol/L; and <50 nmol/L. The Massachusetts Department of Correction Statement of Nutritional Adequacy stated that each inmate received the recommended daily allowance of vitamin D daily. Security level of incarceration was designated as minimum, medium, and maximum. Racial groups were categorized as Black, white, Asian, and Others. Results Serum 25(OH)D levels peaked in summer and autumn, and decreased in winter and spring. Vitamin D deficiency occurred in 50.5% of blacks, 29.3% of whites, and 14.3% of Asian inmates (p = 0.007). Black inmates had significantly lower serum 25(OH)D level than white inmates at the maximum security level (p = 0.015), medium security level (p = 0.001), but not at the minimum security level (p = 0.40). After adjusting for covariates black inmates at a maximum security level had a four-fold higher risk for vitamin D deficiency than white inmates at the same security level (OR 3.9 [95% CI 1.3–11.7]. Conclusions The vitamin D status of prison inmates is determined by skin pigmentation, seasons, and the security level of incarceration.
Optimizing Pin Assignment and Escape Routing for Blind-via-Based PCBs

Pin assignment and escape routing are two closely related problems and it is desired to consider routability during pin assignment for package-board co-design. During pin assignment and escape routing, differential pairs and blind-via usage are two major factors to be considered in modern printed circuit board designs. However, most previous works only target on either differential pairs or blind-via usage but cannot handle both of them simultaneously. In this paper, we propose the first package-board co-design method to optimize the pin assignment and escape routing in the presence of differential pairs and blind-via usage for grid pin array. Experimental results show that our package-board co-design flow can achieve wirelength improvement and reduce the number of layers required compared with competitive baseline flows.
IL-17a and IL-22 Induce Expression of Antimicrobials in Gastrointestinal Epithelial Cells and May Contribute to Epithelial Cell Defense against Helicobacter pylori

Helicobacter pylori colonization of the human stomach can lead to adverse clinical outcomes including gastritis, peptic ulcers, or gastric cancer. Current data suggest that in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization. Specifically, CD4+ T cell responses impact the pathology elicited in response to H. pylori. Because gastritis is believed to be the initiating host response to more detrimental pathological outcomes, there has been a significant interest in pro-inflammatory T cell cytokines, including the cytokines produced by T helper 17 cells. Th17 cells produce IL-17A, IL-17F, IL-21 and IL-22. While these cytokines have been linked to inflammation, IL-17A and IL-22 are also associated with anti-microbial responses and control of bacterial colonization. The goal of this research was to determine the role of IL-22 in activation of antimicrobial responses in models of H. pylori infection using human gastric epithelial cell lines and the mouse model of H. pylori infection. Our data indicate that IL-17A and IL-22 work synergistically to induce antimicrobials and chemokines such as IL-8, components of calprotectin (CP), lipocalin (LCN) and some β-defensins in both human and primary mouse gastric epithelial cells (GEC) and gastroids. Moreover, IL-22 and IL-17A-activated GECs were capable of inhibiting growth of H. pylori in vitro. While antimicrobials were activated by IL-17A and IL-22 in vitro, using a mouse model of H. pylori infection, the data herein indicate that IL-22 deficiency alone does not render mice more susceptible to infection, change their antimicrobial gene transcription, or significantly change their inflammatory response.
Two-way secrecy schemes for the broadcast channel with internal eavesdroppers

The secrecy problem in a broadcast setting with one source and a number of users is considered, where the message to a given user must be kept secret from all of the other users. Multi-user diversity suggests an opportunistic approach that sends a message secretly to the user with the current best channel; however, the secrecy rate goes to zero in the limit of a large number of users. Here, channel reciprocity is exploited via a two-way secrecy scheme to provide a constant positive secrecy rate to the user with the best channel. Next, motivated by the desire to transmit to a given user (rather than opportunistically to the user with the best channel), a second scheme is developed that employs relaying from other users from whom the message is still kept secret. In this non-opportunistic case, a positive secrecy rate is again shown to be achievable in the limit of a large number of system users.
R2-D2 Reloaded: A flexible sound synthesis system for sonic human-robot interaction design

A key skill for social robots is the ability to communicate their inner state to humans. In this paper, we explore abstracted robot-specific ways of interaction as an alternative to human-like or animal-like social cues. In particular, we present a sound system as a novel modality that extends a robot's ability for non-verbal communication. Unlike prior work which used pre-recorded audio samples to this end, we propose a flexible architecture with a generalized sound synthesizer that uses the principle of modulation to shape the sound in real-time by external and internal stimuli from the robot or the interaction. This allows for almost unlimited possibilities in the design of an expressive auditory social cue for human-robot interaction. We instantiate the architecture and report on example design choices for the sound synthesis principle, the real-time synthesizer, the sound modulation routings, and a sound sequence composer. We then demonstrate the system's ability for affect communication of primary and secondary emotions on a social robot.
Functional Neuroimaging Studies of Human Emotions

ABSTRACT Neuroimaging studies with positron emission tomography and functional magnetic resonance imaging have begun to describe the functional neuroanatomy of human emotion. Taken separately, specific studies vary in task dimensions and in type(s) of emotion studied, and are limited by statistical power and sensitivity. By examining findings across studies in a meta-analysis, we sought to determine if common or segregated patterns of activations exist in different emotions and across various emotional tasks. We surveyed over 55 positron emission tomography and functional magnetic resonance imaging activation studies, which investigated emotion in healthy subjects. This paper will review observations in several regions of interest in limbic (eg, amygdala, anterior cingulate cortex) and paralimbic (eg, medial prefrontal cortex, insula) brain regions in emotional responding.
Political Participation and EU Citizenship: Perceptions and Behaviours of Young People

1 Contents Introduction 2 1. Changing patterns of political engagement and new citizenship perceptions: conceptual overview 4 2. Young people and political participation 6 2.1. Effective ways of influencing decision-making: perceptions of young people 6 2.2. Young people's political participation: traditional and new ways of expressing opinions 10 3. Young people and their perception of EU citizenship 13 4.
The adaptive value associated with expressing and perceiving angry-male and happy-female faces

Facial expressions are valuable for conveying and understanding the inner thoughts and feelings of the expressor. However, the adaptive value associated with a specific expression on a male face is different from a female face. The present review uses a functional-evolutionary analysis to elucidate the evolutionary advantage in the expression and perception of angry-male and happy-female faces over angry-female and happy-male faces. For the expressors, it is more advantageous for men to show angry facial expression as it signals dominance, averts aggression and deters mate poaching; it is more advantageous for women to display happy facial expression as it signals their willingness for childcare, tending and befriending. For the perceivers, those sensitive to angry men avoid being physically harmed while those sensitive to happy women gain social support. Extant evidence suggests that facial structure and cognitive mechanisms evolved to express and perceive angry-male and happy-female faces more efficiently compared to angry-female and happy-male faces.
Approximating s – t Minimum Cuts in ~ O(n 2 ) Time

We improve on randomsamplingtechniquesfor approximately solving problems that involve cuts in graphs. We give a linear-time construction that transforms any graph on n vertices into an O(nlogn) -edge graphonthe samevertices whosecutshave approximately the same value as the original graph’s. In this new graph, for example, we can run the ~ O(mn) -time maxi-mumﬂowalgorithm of Goldberg andTarjanto ﬁnd an s – t minimum cut in ~ O(n 2 ) time. This corresponds to a (1 +(cid:15)) -times minimum s – t cut in the original graph. In a similar way, we can approximate a sparsest cut in ~ O(n 2 ) time.
Risk factors for repetition and suicide following self-harm in older adults: multicentre cohort study.

BACKGROUND Older adults have elevated suicide rates. Self-harm is the most important risk factor for suicide. There are few population-based studies of self-harm in older adults. AIMS To calculate self-harm rates, risk factors for repetition and rates of suicide following self-harm in adults aged 60 years and over. METHOD We studied a prospective, population-based self-harm cohort presenting to six general hospitals in three cities in England during 2000 to 2007. RESULTS In total 1177 older adults presented with self-harm and 12.8% repeated self-harm within 12 months. Independent risk factors for repetition were previous self-harm, previous psychiatric treatment and age 60-74 years. Following self-harm, 1.5% died by suicide within 12 months. The risk of suicide was 67 times that of older adults in the general population. Men aged 75 years and above had the highest suicide rates. CONCLUSIONS Older adults presenting to hospital with self-harm are a high-risk group for subsequent suicide, particularly older men.
Efficient implementation of GMM based speaker verification using sorted Gaussian mixture model

In this paper a new structured Gaussian mixture model, called sorted GMM, is proposed as an efficient method to implement GMM-based speaker verification systems; such as Gaussian mixture model universal background model (GMM-UBM) scheme. The proposed method uses a sorted GMM which facilitate partial search and has lower computational complexity and less memory requirement compared to the well-known tree-structured GMM of the same model order. Experimental results show that a speaker verification system based on the proposed method outperforms that of a similar system which uses tree-structured from performance point of view. It also provides comparable performance with the GMM-UBM method despite its 3.5 times lower computational cost for a GMM of order 64.
An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

The crystal and solution structures of the T. thermophilus NlpC/P60 d,l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan.
Intraoffice Variability of Corneal Biomechanical Parameters and Intraocular Pressure (IOP)

Purpose. To evaluate the intraoffice hour variability of intraocular pressure (IOP) and in vivo biomechanical properties of the cornea, as measured with the Ocular Response Analyzer (ORA). Methods. The right eye of each of 58 young healthy subjects (14 men, 44 women) was measured at 1-hour intervals from 9.00 a.m. until 7.00 p.m. with the ORA. Subjects’ age ranged from 19 to 45 years (average ± standard deviation, 25 ± 6 years). Results. Average intraoffice hour variability of IOP and corneal biomechanical parameters were not statistically significant, showing a stable profile during the hours of the day studied. An interesting finding was that although there were no significant diurnal variations in any of the parameters, minor changes in corneal-compensated IOP and a Goldmann-equivalent IOP were significantly correlated with the intraoffice hour variability of corneal biomechanical parameters corneal hysteresis (CH) and the corneal resistance factor (CRF). Corneal-compensated IOP changes were the most strongly associated with intraoffice hour variability in CH for all measurement times (r2 = 0.598; p < 0.001). Changes of Goldmann-equivalent IOP were strongly correlated with intraoffice hour variability of corneal resistance factor (r2 = 0.849; p < 0.001). Conclusions. The present study confirms that intraoffice hour values of CH and corneal resistance factor are quite stable among a population of young healthy adults. However, average changes in these parameters over time correlate well with the changes in IOP values obtained with the same instrument, suggesting that diurnal variations of IOP could be at least in part related with changes in the biomechanical behavior of the cornea against the mechanical stimuli used by current non-contact tonometers. The most stable period to measure IOP and biomechanical parameters with ORA was in the afternoon.
Effect of Heavy Metals in Plants of the Genus Brassica

Several species from the Brassica genus are very important agricultural crops in different parts of the world and are also known to be heavy metal accumulators. There have been a large number of studies regarding the tolerance, uptake and defense mechanism in several of these species, notably Brassica juncea and B. napus, against the stress induced by heavy metals. Numerous studies have also been published about the capacity of these species to be used for phytoremediation purposes but with mixed results. This review will focus on the latest developments in the study of the uptake capacity, oxidative damage and biochemical and physiological tolerance and defense mechanisms to heavy metal toxicity on six economically important species: B. juncea, B. napus, B. oleracea, B. carinata, B. rapa and B. nigra.
Cognitive Metaphor Theory and the Metaphysics of Immediacy

One of the core tenets of cognitive metaphor theory is the claim that metaphors ground abstract knowledge in concrete, first-hand experience. In this paper, I argue that this grounding hypothesis contains some problematic conceptual ambiguities and, under many reasonable interpretations, empirical difficulties. I present evidence that there are foundational obstacles to defining a coherent and cognitively valid concept of "metaphor" and "concrete meaning," and some general problems with singling out certain domains of experience as more immediate than others. I conclude from these considerations that whatever the facts are about the comprehension of individual metaphors, the available evidence is incompatible with the notion of an underlying conceptual structure organized according to the immediacy of experience.
Sensitivity of EMIC Wave‐Driven Scattering Loss of Ring Current Protons to Wave Normal Angle Distribution

Electromagnetic ion cyclotron waves have long been recognized to play a crucial role in the dynamic loss of ring current protons. While the field‐aligned propagation approximation of electromagnetic ion cyclotron waves was widely used to quantify the scattering loss of ring current protons, in this study, we find that the wave normal distribution strongly affects the pitch angle scattering efficiency of protons. Increase of peak normal angle or angular width can considerably reduce the scattering rates of ≤10 keV protons. For >10 keV protons, the field‐aligned propagation approximation results in a pronounced underestimate of the scattering of intermediate equatorial pitch angle protons and overestimates the scattering of high equatorial pitch angle protons by orders of magnitude. Our results suggest that the wave normal distribution of electromagnetic ion cyclotron waves plays an important role in the pitch angle evolution and scattering loss of ring current protons and should be incorporated in future global modeling of ring current dynamics.
Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome

Monozygotic (identical) twins have been widely used in genetic studies to determine the relative contributions of heredity and the environment in human diseases. Discordance in disease manifestation between affected monozygotic twins has been attributed to either environmental factors or different patterns of X chromosome inactivation (XCI). However, recent studies have identified genetic and epigenetic differences between monozygotic twins, thereby challenging the accepted experimental model for distinguishing the effects of nature and nurture. Here, we report the genomic and epigenomic sequences in skin fibroblasts of a discordant monozygotic twin pair with Rett syndrome, an X-linked neurodevelopmental disorder characterized by autistic features, epileptic seizures, gait ataxia and stereotypical hand movements. The twins shared the same de novo mutation in exon 4 of the MECP2 gene (G269AfsX288), which was paternal in origin and occurred during spermatogenesis. The XCI patterns in the twins did not differ in lymphocytes, skin fibroblasts, and hair cells (which originate from ectoderm as does neuronal tissue). No reproducible differences were detected between the twins in single nucleotide polymorphisms (SNPs), insertion-deletion polymorphisms (indels), or copy number variations. Differences in DNA methylation between the twins were detected in fibroblasts in the upstream regions of genes involved in brain function and skeletal tissues such as Mohawk Homeobox (MKX), Brain-type Creatine Kinase (CKB), and FYN Tyrosine Kinase Protooncogene (FYN). The level of methylation in these upstream regions was inversely correlated with the level of gene expression. Thus, differences in DNA methylation patterns likely underlie the discordance in Rett phenotypes between the twins.
Contribution of Notch signaling activation to human glioblastoma multiforme.

OBJECT Because activation of Notch receptors has been suggested to be critical for Ras-mediated transformation, and because many gliomas exhibit deregulated Ras signaling, the authors measured Notch levels and activation in primary samples and cell lines derived from glioblastoma multiforme (GBM) as well as the contribution of Notch pathway activation to astrocytic transformation and growth. METHODS Western blot analysis of Notch 1 expression and activation showed that Notch 1 protein was overexpressed and/or activated in Ras-transformed astrocytes, in three of four GBM cell lines, and in four of five primary GBM samples. Expansion of these studies to assess mRNA expression of components of the Notch signaling pathway by cDNA expression array showed that cDNAs encoding components of the Notch signaling pathway, including the Notch ligand Jagged-1, Notch 3, and the downstream targets of Notch (HES1 and HES2), were also overexpressed relative to non-neoplastic brain controls in 23, 71, and 51% of 35 primary GBMs, respectively. Furthermore, inhibition of Notch signaling by genetic or pharmacological means led to selective suppression of the growth and expression of markers of differentiation in cells exhibiting Notch pathway deregulation. CONCLUSIONS Notch activation contributes to Ras-induced transformation of glial cells and to glioma growth, survival, or both and as such may represent a new target for GBM therapy.
Formation of Sulfonyl Aromatic Alcohols by Electrolysis of a Bisazo Reactive Dye

Five sulfonyl aromatic alcohols, namely 4-((2-hydroxyethyl)sulfonyl)phenol, 4-((2-(2-((4-hydroxyphenyl)sulfonyl)ethoxy)vinyl)sulfonyl)phenol, 4-(ethylsulfonyl)phenol, 4-(vinylsulfonyl)phenol and 5-((4-aminophenyl)sulfonyl)-2-penten-1-ol were identified by LC-ESI-Qq-TOF-MS as products formed by electrolysis of the bisazo reactive dye Reactive Black 5 (RB5). Since electrolyses were performed in an undivided cell equipped with Ni electrodes in alkaline medium, amines like 4-(2-methoxyethylsulfonyl)benzene-amine (MEBA) with m/z 216 were also suspected to be formed due to the plausible chemical reaction in the bulk or the cathodic reduction of RB5 and its oxidation by-products. Aiming to check this hypothesis, a method was used for the preparation of MEBA with 98% purity, via chemical reduction also of the dye RB5. The logP of the synthesized sulfonyl aromatic compounds was calculated and their logkw values were determined chromatographically. These data were discussed in regard to the relationship between hydrophobicity/lipophilicity and toxicity.