Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Characterization and Comparison of Intercellular Communication in Stem Cell‐Derived Cardiomyocytes

One novel treatment strategy for the diseased heart focuses on the use of pluripotent stem cell‐derived cardiomyocytes (SC‐CMs) to overcome the heart's innate deficiency for self‐repair. However, targeted application of SC‐CMs requires in‐depth characterization of their true cardiogenic potential in terms of excitability and intercellular coupling at cellular level and in multicellular preparations. In this study, we elucidated the electrical characteristics of single SC‐CMs and intercellular coupling quality of cell pairs, and concomitantly compared them with well‐characterized murine native neonatal and immortalized HL‐1 cardiomyocytes. Firstly, we investigated the electrical properties and Ca2+ signaling mechanisms specific to cardiac contraction in single SC‐CMs. Despite heterogeneity of the new cardiac cell population, their electrophysiological activity and Ca2+ handling were similar to native cells. Secondly, we investigated the capability of paired SC‐CMs to form an adequate subunit of a functional syncytium and analyzed gap junctions and signal transmission by dye transfer in cell pairs. We discovered significantly diminished coupling in SC‐CMs compared with native cells, which could not be enhanced by a coculture approach combining SC‐CMs and primary CMs. Moreover, quantitative and structural analysis of gap junctions presented significantly reduced connexin expression levels compared with native CMs. Strong dependence of intercellular coupling on gap junction density was further confirmed by computational simulations. These novel findings demonstrate that despite the cardiogenic electrophysiological profile, SC‐CMs present significant limitations in intercellular communication. Inadequate coupling may severely impair functional integration and signal transmission, which needs to be carefully considered for the prospective use of SC‐CMs in cardiac repair. Stem Cells 2015;33:2208–2218
A consideration of what is meant by automaticity and better ways to measure it

Existing models of exercise behavior are insufficient in predicting outcomes, this point is shown by the relatively high levels of unexplained variance in exercise behavior in meta-analyses of social cognitive theories and models (Chatzisarantis et al., 2003; Hagger and Chatzisarantis, 2009). Researchers are beginning to recognize the importance of implicit, automatic processes in the prediction of health behaviors (Dimmock and Banting, 2009; Keatley et al., 2012, 2013b). The research by de Bruijn et al. (2014) is useful for highlighting the importance of automaticity in exercise behavior. We commend the authors on investigating an important approach to automaticity and exercise behavior. There were, however, some points with which we disagree. We think that the authors do not provide a clear account of what they mean by automaticity–an issue that is essential for the operationalization of the construct. Bargh (1994), for instance, suggested automaticity has four characteristics: awareness, intention, efficiency, and control; it is not clear whether de Bruijn and colleagues automaticity adheres to this. In particular, we contend that the explicit measure of automaticity used in their research is not an optimal way to assess implicit, impulsive processes. Furthermore, we contend that implicit measures, such as the implicit association test (IAT; Greenwald et al., 1998) would be better positioned as measures of non-conscious processes. The present commentary focuses on pre-behavior automatic associations, which we contend are better assessed by existing implicit measures, rather than during-behavior automatic “processes. ”
Using “Annotator Rationales” to Improve Machine Learning for Text Categorization

We propose a new framework for supervised machine learning. Our goal is to learn from smaller amounts of supervised training data, by collecting a richer kind of training data: annotations with “rationales. ” When annotating an example, the human teacher will also highlight evidence supporting this annotation—thereby teaching the machine learner why the example belongs to the category. We provide some rationale-annotated data and present a learning method that exploits the rationales during training to boost performance significantly on a sample task, namely sentiment classification of movie reviews. We hypothesize that in some situations, providing rationales is a more fruitful use of an annotator’s time than annotating more examples.
Subcuticular bacteria from the brittle star Ophiactis balli (Echinodermata: Ophiuroidea) represent a new lineage of extracellular marine symbionts in the alpha subdivision of the class Proteobacteria

Many species of echinoderms, in all five extant classes, contain subcuticular bacterial symbionts (SCB). The role of these extracellular symbionts and the nature of the relationship remain unclear. We have sequenced 16S rRNA genes from symbionts to determine their phylogenetic affinities. Symbionts of an ophiuroid, Ophiactis balli, appear closely related to bacteria within the alpha group of the class Proteobacteria, including intracellular endosymbionts and pathogens. SCB are clearly of separate origin from other documented major groups of marine symbiotic bacteria.
Crystal Structures of the Sec1/Munc18 (SM) Protein Vps33, Alone and Bound to the Homotypic Fusion and Vacuolar Protein Sorting (HOPS) Subunit Vps16*

Intracellular membrane fusion requires the regulated assembly of SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor) proteins anchored in the apposed membranes. To exert the force required to drive fusion between lipid bilayers, juxtamembrane SNARE motifs zipper into four-helix bundles. Importantly, SNARE function is regulated by additional factors, none more extensively studied than the SM (Sec1/Munc18-like) proteins. SM proteins interact with both individual SNAREs and SNARE complexes, likely chaperoning SNARE complex formation and protecting assembly intermediates from premature disassembly by NSF. Four families of SM proteins have been identified, and representative members of two of these families (Sec1/Munc18 and Sly1) have been structurally characterized. We report here the 2.6 Å resolution crystal structure of an SM protein from the third family, Vps33. Although Vps33 shares with the first two families the same basic three-domain architecture, domain 1 is displaced by 15 Å, accompanied by a 40° rotation. A unique feature of the Vps33 family of SM proteins is that its members function as stable subunits within a multi-subunit tethering complex called HOPS (homotypic fusion and vacuolar protein sorting). Integration into the HOPS complex depends on the interaction between Vps33 and a second HOPS subunit, Vps16. The crystal structure of Vps33 bound to a C-terminal portion of Vps16, also at 2.6 Å resolution, reveals the structural basis for this interaction. Despite the extensive interface between the two HOPS subunits, the conformation of Vps33 is only subtly affected by binding to Vps16.
TACC3 is a microtubule plus end–tracking protein that promotes axon elongation and also regulates microtubule plus end dynamics in multiple embryonic cell types

TACC3 is a microtubule plus end–tracking protein in vertebrates. TACC3 localizes to the extreme microtubule plus end, where it interacts with XMAP215 to regulate microtubule polymerization. TACC3 is also required to promote normal axon outgrowth, likely through its regulation of microtubule dynamics within the growth cone.
Peritoneal transport: getting more complicated

A high clearance of low-molecular substances such as urea and creatinine is generally considered advantageous in dialysis. The discovery in the 1990s of increased morbidity [1] and mortality [2, 3] in peritoneal dialysis (PD) patients with fast low-molecular (e.g. glucose, creatinine and urea) peritoneal transport (FLMT, also called ‘high transport’) was thus counterintuitive. Several explanations are possible:
Bioequivalence of Dispersed Stavudine: Opened versus Closed Capsule Dosing

Background Stavudine, a nucleoside reverse transcriptase inhibitor, is used commonly to treat HIV-infected children in the developing world. The paediatric liquid formulation presents major logistical difficulties in rural and resource-limited areas, and prescribers are frequently forced to employ off-label ‘opened capsule’ dosing methods using the adult capsule. The South African Department of Health (DoH) has advised that caregivers should be instructed to disperse the contents of an adult capsule in 5 ml water and then withdraw the required dose using a syringe. The bioavailability of stavudine using the opened capsule dosing method has not previously been validated. Methods This was a randomized crossover pharmacokinetic study with each subject serving as his/her own control. A total of 28 healthy HIV-negative adult volunteers were randomized on a 1:1 basis to receive one of the two generic preparations typically available in state hospitals. They were then further randomized to receive either intact or opened 30 mg capsules. After 1 week, those who initially received intact capsules, were given opened capsules and vice versa. The capsule dispersion technique used was identical to that prescribed by the DoH. Serial blood samples were collected and plasma stavudine concentrations were assayed by liquid chromatography tandem mass spectrometry. Stavudine pharmacokinetics were analysed using non-compartmental methods and formulations were compared using ANOVA. Results Plasma drug exposure after stavudine administration as a solution using an opened capsule dosing method was found to be bioequivalent to intact capsule administration. This was true for both generics tested. Conclusions The opened capsule dosing technique is bio-equivalent to intact capsule dosing for stavudine in HIV-seronegative adults.
First-in-Man Demonstration of Direct Endothelin-Mediated Natriuresis and Diuresis

Endothelin (ET) receptor antagonists are potentially novel therapeutic agents in chronic kidney disease and resistant hypertension, but their use is complicated by sodium and water retention. In animal studies, this side effect arises from ETB receptor blockade in the renal tubule. Previous attempts to determine whether this mechanism operates in humans have been confounded by the hemodynamic consequences of ET receptor stimulation/blockade. We aimed to determine the effects of ET signaling on salt transport in the human nephron by administering subpressor doses of the ET-1 precursor, big ET-1. We conducted a 2-phase randomized, double-blind, placebo-controlled crossover study in 10 healthy volunteers. After sodium restriction, subjects received either intravenous placebo or big ET-1, in escalating dose (⩽300 pmol/min). This increased plasma concentration and urinary excretion of ET-1. Big ET-1 reduced heart rate (≈8 beats/min) but did not otherwise affect systemic hemodynamics or glomerular filtration rate. Big ET-1 increased the fractional excretion of sodium (from 0.5 to 1.0%). It also increased free water clearance and tended to increase the abundance of the sodium–potassium–chloride cotransporter (NKCC2) in urinary extracellular vesicles. Our protocol induced modest increases in circulating and urinary ET-1. Sodium and water excretion increased in the absence of significant hemodynamic perturbation, supporting a direct action of ET-1 on the renal tubule. Our data also suggest that sodium reabsorption is stimulated by ET-1 in the thick ascending limb and suppressed in the distal renal tubule. Fluid retention associated with ET receptor antagonist therapy may be circumvented by coprescribing potassium-sparing diuretics.
TMop: a Tool for Unsupervised Translation Memory Cleaning

We present TMop, the first open-source tool for automatic Translation Memory (TM) cleaning. The tool implements a fully unsupervised approach to the task, which allows spotting unreliable translation units (sentence pairs in different languages, which are supposed to be translations of each other) without requiring labeled training data. TMop includes a highly configurable and extensible set of filters capturing different aspects of translation quality. It has been evaluated on a test set composed of 1,000 translation units (TUs) randomly extracted from the English-Italian version of MyMemory, a large-scale public TM. Results indicate its effectiveness in automatic removing “bad” TUs, with comparable performance to a state-of-the-art supervised method (76.3 vs. 77.7 balanced accuracy).
Effect of Deep Cryogenic Treatment on the Carbide Precipitation and Tribological Behavior of D2 Steel

The influence of deep cryogenic processing in between quenching and tempering (QCT) on the carbide precipitation and the tribological behavior of a commercial AISI D2 steel has been examined. The developed microstructures have been characterized with an emphasis to understand the influence of QCT vis-à-vis conventional quenching and tempering (QT) on the nature, size, morphology, and distribution of carbide particles. The mechanical properties such as hardness and wear resistance of the samples treated by QT and QCT have been evaluated employing Vickers indentation and sliding wear techniques, respectively. It has been demonstrated that deep cryogenic treatment leads to considerable microstructural changes which result in enhanced tribological properties.
Imaging growth of thick engineered tissues with fluorescence diffuse optical tomography

Recent advances in tissue engineering (TE) aim to grow 3D volumes of tissue in bioreactor conditions. This has proved to be a difficult task thus far, notably due to the lack of non-invasive diagnostic tools to monitor the growth of a tissue and ensure its appropriate development. To fulfill part of this need, we currently develop a non-invasive imaging technique based on fluorescence diffuse optical tomography (FDOT) to image in 3D, via fluorescent tracers, processes relevant to tissue growth in a bioreactor. More particularly, here we are interested in imaging the formation of micro-blood vessels in tissue cultures grown on biodegradable scaffolds. Blood vessels are thought to play a fundamental role in tissue growth. Since a bioreactor possesses a known geometry (by design), we propose an FDOT configuration that uses fiber optics brought in contact with the boundary of the bioreactor to collect tomographic optical data. We describe an optical fibers-based set-up and experimental measurements that demonstrate the possibility of localizing a fluorophore-filled 500&mgr;m capillary immersed in a scattering medium contained in a cylindrically-shaped glass tube. These conditions are representative of experiments to be carried on real tissue cultures. In our particular implementation, time-resolved scattering- fluorescence measurements are made via time-correlated single photon counting. Numerical constant fraction discrimination applied to our time-resolved data allows to extract primary localization information.
Subtle motor disturbances in PREDICT-PD participants

Objective The PREDICT-PD study aims to identify increased risk of Parkinson’'s disease (PD) using online assessments of previously identified risk and early features of PD and an evidence-based scoring algorithm. We sought to determine whether higher risk participants (defined as those above the 15th centile of risk estimates) were more likely to have mild parkinsonian signs compared with lower risk participants. Methods Video recordings of neurological examinations, including the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III, of 208 individuals who had previously completed an online risk assessment were scored blindly and independently by two movement-disorders experts. Higher risk and lower risk subjects were compared for MDS-UPDRS part III score (and derivations of this) to identify subclinical parkinsonism, and association of risk estimates with MDS-UPDRS III scores assessed. Results Higher risk subjects had significantly higher median UPDRS part III scores (3, IQR 1–5.5) than lower risk subjects (1, IQR 0–3.0; p<0.001), and there was a significantly greater proportion of individuals classified as having subclinical parkinsonism. 18% of the higher risk subjects and 6% of the lower risk subjects exceeded the most stringent published cut-off for subtle parkinsonism of three definitions examined (p=0.027). Linear regression analysis demonstrated a continuous relationship of log-transformed risk estimates with UPDRS part III scores (increase in MDS-UPDRS per doubling of odds 0.52, 95% CI 0.31 to 0.72; p<0.001), which remained after adjustment for multiple vascular risk factors and scores on the Montreal Cognitive Assessment (0.58, 95% CI 0.30 to 0.87; p<0.001). Conclusions The PREDICT-PD algorithm identifies a population with an increased rate of motor disturbances.
Approximate analysis of the interfacial stress concentrations in FRP–RC hybrid beams

In this paper an approximate analytical method is proposed to predict the distribution of interfacial stresses in FRP–RC hybrid beams. The theoretical results are compared, and show close agreement, with other rigorous theoretical analyses. A parametrical study is carried out to show the effects of some design variables, e.g. thickness of adhesive layer, thickness of FRP plate and the distance from support to cut-off end of bonded plates.
Separating retrieval strategies from retrieval success ] an event ! related potential study of source memory

Event! related potentials "ERPs# were recorded while subjects performed two di}erent source memory retrieval tasks[ Each task was preceded by a study phase in which subjects heard an equal number of words spoken in a male or a female voice[ A cue preceding each word indicated whether the subjects should make an active:passive "action# or a pleasant:unpleasant "liking# judgment to the word[ In one retrieval task "the voice condition#\ subjects made a three! way distinction between new "unstudied# words\ and words that had been spoken by the male or the female voice at study[ In the second retrieval task "the task condition#\ subjects distinguished between new words\ and words to which they had made an action or a liking judgment[ All test words were presented visually[ In keeping with previous _ndings\ the di}erences between the ERPs to correct memory judgments for old and new items were characterised by two temporally and topographically dissociable modulations\ with right! frontal and left! parietal maxima respec! tively[ These {old:new e}ects| displayed di}erent sensitivities to successful retrieval of either voice or task information\ providing further evidence that they index functionally dissociable processes[ The direct comparison of the ERPs to correct rejections in the voice and task retrieval conditions revealed reliable di}erences over frontal scalp\ suggesting that\ irrespective of whether retrieval is successful\ neural processing di}ers according to the source retrieval demands of the task[ Þ 0888 Elsevier Science Ltd[ All rights reserved[ Source memory refers to memory for information that speci_es the conditions under which memories were acquired ð04Ł[ This includes details of spatial\ temporal and social context\ and information about the modalities through which events were initially perceived[ The results of studies with brain damaged patients ð00\ 21\ 23Ł\ as well as behavioural ð8Ł and event! related potential studies in normal subjects ð30Ł\ are consistent with the view that memory for source involves at least two distinct sets of processes[ One in~uential proposal is that these processes are associated with information retrieval\ and with post! retrieval mechanisms necessary for recovery of accurate source information ð12\ 24Ł[ This two! stage description of memory for source is evident in the source monitoring framework "SMF# of Johnson and colleagues ð04\ 06Ł\ which emphasises the strategic use of memory[ In the SMF it is assumed that source judgments can be made by assessing the dis! Fax] ¦33 90754 209336^ e! mail] edward[wildingÝpsy[ox[ac[uk tribution of various qualitative characteristics of a mem! ory trace\ which should di}er …
Characterization of the emitting and absorbing media around the nucleus of the active galaxy UGC 11763 using XMM-Newton data

This is an electronic version of an article published in Astronomy and Astrophysics. Cardaci, M.V. , Santos-Lleo, M. , Krongold, Y. , Hagele, G.F. , Diaz, A.I. and P. Rodriguez-Pascual. Characterization of the emitting and absorbing media around the nucleus of the active galaxy UGC 11763 using XMM-Newton data. Astronomy and Astrophysics 505 (2009): 541-551
Innovation strategies and firm performance: Simple or complex strategies?

ABSTRACT This paper analyzes the effect of various innovation strategies (ISs) of firms on their future performance, captured by labor productivity. Using five waves of the Community Innovation Survey in Sweden, we have traced the innovative behavior of firms over a decade, that is, from 2002 to 2012. We defined ISs to be either simple or complex (in various degrees). We call an IS a simple IS when firms engage in only one of the four types of Schumpeterian innovations, that is, product, process, marketing, or organizational, while a complex IS is when firms simultaneously engage in more than one type. The main findings indicate that those firms that choose and afford to have complex ISs are better off in terms of their future productivity in comparison with those firms that choose not to innovative (base group) and also in comparison with those firms that choose simple ISs. The results are mostly robust for those complex innovators that have a higher degree of complexity and also keep the balance between technological (product and process) and non-technological (organizational and marketing) innovations.
Risk of suicide, deliberate self‐harm and psychiatric illness after the loss of a close relative: A nationwide cohort study

The loss of a close relative is a common event, yet it is associated with increased risk of serious mental health conditions. No large‐scale study has explored up to now the importance of the bereaved person's relation to the deceased while accounting for gender and age. We performed a nationwide Danish cohort study using register information from 1995 through 2013 on four sub‐cohorts including all persons aged ≥18 years exposed to the loss of a child, spouse, sibling or parent. We identified 1,445,378 bereaved persons, and each was matched by gender, age and family composition to five non‐bereaved persons. Cumulative incidence proportions were calculated to estimate absolute differences in suicide, deliberate self‐harm and psychiatric illness. Cox proportional hazard regression was used to calculate hazard ratios while adjusting for potential confounders. Results revealed that the risk of suicide, deliberate self‐harm and psychiatric illness was increased in the bereaved cohorts for at least 10 years after the loss, particularly during the first year. During that year, the risk difference was 18.9 events in 1,000 persons after loss of a child (95% CI: 17.6‐20.1) and 16.0 events in 1,000 persons after loss of the spouse (95% CI: 15.4‐16.6). Hazard ratios were generally highest after loss of a child, in younger persons, and after sudden loss by suicide, homicide or accident. One in three persons with a previous psychiatric diagnosis experienced suicide, deliberate self‐harm or psychiatric illness within the first year of bereavement. In conclusion, this study shows that the risk of suicide, deliberate self‐harm and psychiatric illness is high after the loss of a close relative, especially in susceptible subgroups. This suggests the need for early identification of high‐risk persons displaying adjustment problems after loss of a close family member, in order to reduce the risk of serious mental health outcomes.