Miracle-dz/UniFAR-FTUs huggingface dataset:
Mesenchymal stromal cells from donors varying widely in age are of equal cellular fitness after in vitro expansion under hypoxic conditions.

BACKGROUND AIMS Mesenchymal stromal cells (MSC) are gaining in popularity as an experimental therapy for a number of conditions that often require expansion ex vivo prior to use. Data comparing clinical-grade MSC from various ages of donors are scant. We hypothesized that MSC from older donors may display differences in cellular fitness when expanded for clinical use. METHODS We evaluated the expression of several markers of aging, oxidative stress and growth kinetics, and telomere length, in MSC obtained from a wide age range (8 months to 58 years). RESULTS To evaluate cellular fitness we compared MSC expanded from younger (8 months-6 years) versus older (38-58 years) donors in terms of selected cell-surface markers, lipofuscin, migration ability, telomere length and expression of iNOS, PGE₂, p16INK and SOD. Results did not differ between these groups. Neither SOD activity (0.025 versus 0.028 U/mL) nor death after oxidative challenge was significantly different (1% versus 1.5%, P = 0.14). We did find that, although MSC from older individuals produced slightly fewer cells over a 28-day culture period and had a slightly longer doubling time (54 h versus 42 hr, a satisfactory clinical product could still be obtained regardless of age cohort. CONCLUSIONS Collectively, these data show that MSC can be expanded without significant alterations in expansile properties or obvious changes in parameters associated with senescence. Because cellular fitness was equivalent in these cohorts, MSC from donors up to age 58 years can be used as a source of cells for cellular therapy.
Neurokinin Band speci ® c tachykinin NK 3 receptor agonists-induced airway hyperresponsiveness in the guinea-pig 1

1 The aim of this study was to determine whether neurokinin B (NKB) or speci®c agonists of tachykinin NK3 receptors, [MePhe ]NKB and senktide, were able to induce airway hyperresponsiveness in guinea-pigs. The eects of these compounds were compared to those of substance P (SP), neurokinin A (NKA) and the preferential tachykinin NK1 ([Sar , Met(02) ]SP) or NK2 ([bAla]NKA (4-10)) receptor agonists. 2 In guinea-pigs pretreated with phosphoramidon (10 M aerosol for 10 min) and salbutamol (8.7610 M for 10 min), all tachykinins administrated by aerosol (3610 to 10 M) induced airway hyperresponsiveness 24 h later, displayed by an exaggerated response to the bronchoconstrictor eect of acetylcholine (i.v.). The rank order of potency was: [bAla]NKA (410)4NKA=NKB=senktide=[MePhe]NKB=[Sar,Met(02)]SP4SP. 3 Airway hyperresponsiveness induced by [MePhe]NKB was prevented by the tachykinin NK3 (SR 142801) and NK2 (SR 48968) receptor antagonists. 4 Bronchoconstriction induced by tachykinins administered by aerosol was also determined. SP, NKA, NKB and the tachykinin NK1 and NK2 receptor agonist induced bronchoconstriction. The rank order of potency was: NKA=[bAla]NKA (4-10)4NKB=SP=[Sar,Met(02)]SP. Under similar conditions, and for concentrations which induce airway hyperresponsiveness, senktide and [MePhe]NKB failed to induce bronchoconstriction. 5 It is concluded that tachykinin NK3-receptor stimulation can induce airway hyperresponsiveness and that this eect is not related to the ability of tachykinins to induce bronchoconstriction. British Journal of Pharmacology (2000) 130, 49 ± 56
Non-homologous end joining in class switch recombination: the beginning of the end

Immunoglobulin class switch recombination (CSR) is initiated by a B-cell-specific factor, activation-induced deaminase, probably through deamination of deoxycytidine residues within the switch (S) regions. The initial lesions in the S regions are subsequently processed, resulting in the production of DNA double-strand breaks (DSBs). These breaks will then be recognized, edited and repaired, finally leading to the recombination of the two S regions. Two major repair pathways have been implicated in CSR, the predominant non-homologous end joining (NHEJ) and the alternative end-joining (A-EJ) pathways. The former requires not only components of the ‘classical’ NHEJ machinery, i.e. Ku70/Ku80, DNA-dependent protein kinase catalytic subunit, DNA ligase IV and XRCC4, but also a number of DNA-damage sensors or adaptors, such as ataxia–telangiectasia mutated, γH2AX, 53BP1, MDC1, the Mre11–Rad50–NBS1 complex and the ataxia telangiectasia and Rad3-related protein (ATR). The latter pathway is not well characterized yet and probably requires microhomologies. In this review, we will focus on the current knowledge of the predominant NHEJ pathway in CSR and will also give a perspective on the A-EJ pathway.
A 5-year follow-up study of generalized anxiety disorder and panic disorder.

To examine the course and outcome of subjects with generalized anxiety disorder (GAD) and panic disorder, we compared 64 patients with GAD and 68 patients with panic disorder who had participated in drug treatment studies and were interviewed an average of 5 years earlier. At baseline GAD subjects were significantly older, had an earlier onset, and longer duration of illness than panic subjects. GAD subjects also had less severe symptoms. At follow-up, diagnostic stability was observed for both GAD and panic disorder. Significantly fewer GAD subjects achieved full remission at follow-up (18% vs. 45%, p < .01). Subjects with GAD were significantly less anxious at baseline than the panic disorder comparison group, but at follow-up there were few significant differences between groups on most severity of illness variables. This change was due in great part to improvement in the panic disorder group with a concomitant lack of change in the GAD group.
The Concavity of Rényi Entropy Power

We associate to the pth Rényi entropy a definition of entropy power, which is the natural extension of Shannon's entropy power and exhibits a nice behavior along solutions to the p-nonlinear heat equation in Rn. We show that the Rényi entropy power of general probability densities solving such equations is always a concave function of time, whereas it has a linear behavior in correspondence to the Barenblatt source-type solutions. This result extends Costa's concavity inequality for Shannon's entropy power to Rényi entropies.
Factors Influencing the Statistical Power of Complex Data Analysis Protocols for Molecular Signature Development from Microarray Data

Background Critical to the development of molecular signatures from microarray and other high-throughput data is testing the statistical significance of the produced signature in order to ensure its statistical reproducibility. While current best practices emphasize sufficiently powered univariate tests of differential expression, little is known about the factors that affect the statistical power of complex multivariate analysis protocols for high-dimensional molecular signature development. Methodology/Principal Findings We show that choices of specific components of the analysis (i.e., error metric, classifier, error estimator and event balancing) have large and compounding effects on statistical power. The effects are demonstrated empirically by an analysis of 7 of the largest microarray cancer outcome prediction datasets and supplementary simulations, and by contrasting them to prior analyses of the same data. Conclusions/Significance The findings of the present study have two important practical implications: First, high-throughput studies by avoiding under-powered data analysis protocols, can achieve substantial economies in sample required to demonstrate statistical significance of predictive signal. Factors that affect power are identified and studied. Much less sample than previously thought may be sufficient for exploratory studies as long as these factors are taken into consideration when designing and executing the analysis. Second, previous highly-cited claims that microarray assays may not be able to predict disease outcomes better than chance are shown by our experiments to be due to under-powered data analysis combined with inappropriate statistical tests.
A Unified Methodology For Constructing Public-Key Encryption Schemes Secure Against Adaptive Chosen-Ciphertext Attack

We introduce a new methodology for achieving security again st adaptive chosen-ciphertext attack (CCA) for public-key encryption schemes, which we call the oblivious decryptors model . The oblivious decryptors model generalizes both the two-key model of Naor and Yung, as well the Cramer–Shoup encryption schemes. The key ingredient in our new paradigm i s Sahai’s notion of Simulation-Sound NIZK proofs. Our methodology is easy to use: First, construct an encrypti on scheme which satisfies the “bare” oblivious-decryptors model: This can be done quite easily, with simple proofs of security. Then, by adding a Simulation-Sound NIZK proof, the scheme becomes pr ovably CCA-secure. Note that this paradigm allows for the use of efficientspecial-purpose Simulation-Sound NIZK proofs, such as tho e recently put forward by Cramer and Shoup. We also show how to p resent all known efficient (provably secure) CCA-secure public-key encryption schemes as speci al cases of our model.
Is Primitive AV Coherence An Aid To Segment The Scene?

In this paper we propose the existence of an audiovisual scene analysis (AVSA) module which is able to integrate primitive information from both auditory and visual modalities. This module forms correspondences between the auditory and visual streams based on primitive properties of either representation. Through these correspondences visual information is employed to aid the segregation of acoustic sources. This enhanced segregation may be partly responsible for the increased intelligibility of audio-visual speech. The paper presents the initial results of a planned series of audio-visual speech experiments designed to test this account. Speci cally, the experiments reported here address the question of whether visible movement of the speech articulators may protect speech from the e ects of masking by noise. It is shown that a reduction in temporal uncertainty due to visual information may reduce the detection threshold for CVs in noise. The same performance increase was not observed in a parallel experiment testing consonant identi cation.
Adaptive Estimation of Three-Dimensional Structure in the Human Brain

Perceiving the three-dimensional (3D) properties of the environment relies on the brain bringing together ambiguous cues (e.g., binocular disparity, shading, texture) with information gained from short- and long-term experience. Perceptual aftereffects, in which the perception of an ambiguous 3D stimulus is biased away from the shape of a previously viewed stimulus, provide a sensitive means of probing this process, yet little is known about their neural basis. Here, we investigate 3D aftereffects using psychophysical and functional MRI (fMRI) adaptation paradigms to gain insight into the cortical circuits that mediate the perceptual interpretation of ambiguous depth signals. Using two classic bistable stimuli (Mach card, kinetic depth effect), we test aftereffects produced by 3D shapes defined by binocular (disparity) or monocular (texture, shading) depth cues. We show that the processing of ambiguous 3D stimuli in dorsal visual cortical areas (V3B/KO, V7) and posterior parietal regions is modulated by adaptation in line with perceptual aftereffects. Similar behavioral and fMRI adaptation effects for the two types of bistable stimuli suggest common neural substrates for depth aftereffects independent of the inducing depth cues (disparity, texture, shading). In line with current thinking about the role of adaptation in sensory optimization, our findings provide evidence that estimation of 3D shape in dorsal cortical areas takes account of the adaptive context to resolve depth ambiguity and interpret 3D structure.
Continuous Speech Recognition of Japanese Using Prosodic Word Boundaries Detected by Mora Transition Modeling of Fundamental Frequency Contours

An HMM-based method of detecting prosodic word boundaries was developed for Japanese continuous speech and was successfully integrated into a mora-basis continuous speech recognition system with two stages operating without and with prosodic information. The method is based on modeling the fundamental frequency (F0) contour of input speech as transitions of mora-unit F0 contours and operates after receiving mora boundary information form the 1st stage of the recognition system. The 1st and the 2nd stages use different mora bi-gram models as their language models: one trained not taking prosodic word boundary location into account and the other taking into account. Because of perplexity reduction of the model from the 1st to the 2nd stages, an improved recognition result can be obtained from the 2nd stage. In the current paper, the method is explained with experimental results. Issues of grammar scale factor for the boundary detection and N-best scheme for the speech recognition are also included. Improvements in mora recognition rates from the 1st to the 2nd stages were observable in both speaker-closed and –open experiments.
Sodium Valproate Inhibits the Growth of Human Cholangiocarcinoma In Vitro and In Vivo

Background. None of treatment options for Cholangiocarcinoma (CCA), including surgery, adjuvant radiotherapy and chemotherapy, and ultimately liver transplantation, have been shown to substantially improve the survival rate in patients with CCA. Valproic acid (VPA), a histone deacetylase inhibitor, has been shown to display potent antitumor effects. In this study, sodium valproate, the clinically available form of VPA, was tested for its ability to inhibit the growth of cholangiocarcinoma cells, both in vitro and in vivo. Materials and Methods. Cholangiocarcinoma cells (TFK-1, QBC939, and CCLP1) of different origins were treated with sodium valproate to determine their effects on cell proliferation and differentiation, cell cycle regulation, apoptosis, and autophagy. The in vivo effects of sodium valproate on cholangiocarcinoma growth were assessed using a xenograft mouse model injected with TFK-1 cells. Results. Sodium valproate inhibited cholangiocarcinoma cell growth by inducing cell cycle arrest, cell differentiation, and apoptosis; sodium valproate effects were independent of autophagy. Tumor growth inhibition was also observed in vivo using TFK-1 xenografts. Conclusion. The in vitro and in vivo outcomes provide preclinical rationale for clinical evaluation of sodium valproate, alone or in combination with other drugs, to improve patient outcome in cholangiocarcinoma.
The effects of hypoxia on the theoretical modelling of tumour control probability

Theoretical modelling of tumour response is increasingly used for the prediction of treatment result and has even been proposed as ranking criteria in some algorithms for treatment planning. Tumour response to radiation is greatly influenced by the details of tumour microenvironment, especially hypoxia, that unfortunately are not always taken into consideration for these simulations. This paper intends to investigate the effects of various assumptions regarding hypoxia distribution in tumours on the predictions of treatment outcome. A previously developed model for simulating theoretically the oxygenation in biologically relevant tissues, including results from oxygen diffusion, consumption and perfusion limitations in tumours, was used to investigate the effects of the different aspects of hypoxia on the predictions of treatment outcome. Thus, both the continuous distribution of values and the temporal variation of hypoxia patterns were taken into consideration and were compared with a ‘black-and-white’ simplification with a fully hypoxic compartment and a fully oxic one. It was found that the full distribution of oxygenation in the tissue is needed for accurate results. The ‘black-and-white’ simplification, while showing the same general trends for the predictions of radiation response, could lead to serious overestimations of the tumour control probability. It was also found that the presence of some hypoxia for every treatment fraction leads to a decrease in the predicted local control, regardless of the change of the hypoxic pattern throughout the duration of the whole treatment. The results thus suggest that the assumptions regarding tumour hypoxia influence very much the predictions of treatment outcome and therefore they have to be very carefully incorporated into the theoretical modelling.
Depressive symptomatology, weight status and obesogenic risk among Australian adolescents: a prospective cohort study

Objectives Adolescence is a period of increased risk for mental health problems and development of associated lifestyle risk behaviours. This study examined cross-sectional and longitudinal associations between obesogenic risk factors, weight status, and depressive symptomatology in a cohort of Australian adolescents. Design Prospective cohort study. Setting The study used repeated measures data from the Australian Capital Territory (ACT) It's Your Move project, an Australian community-based obesity prevention intervention. Intervention effect was non-significant therefore intervention and comparison groups were combined in this study. Participants Total sample was 634 secondary school students (female n=338, male n=296) with mean age 13 years (SD=0.6) at baseline (2012) and 15 years (SD=0.6) at follow-up (2014) recruited from 6 government secondary schools in the ACT. Primary and secondary outcomes measures Primary outcome was depressive symptomatology measured by Short Mood and Feelings Questionnaire. Secondary outcomes were weight status, physical activity, screen time and diet related measures. Results Increased physical activity was associated to lower depressive symptomatology among males (OR=0.35, p<0.05). Sweet drink (OR=1.15, p<0.05) and takeaway consumption (OR=1.84, p<0.05) were associated with higher levels of depressive symptomatology among females at follow-up. Males who were classified as overweight or obese at baseline, and remained so over the study period, were at increased risk of depressive symptomatology at follow-up (b=1.63, 95% CI 0.33 to 2.92). Inactivity among males over the 2-year study period was predictive of higher depressive symptomatology scores at follow-up (b=2.55, 95% CI 0.78 to 4.32). For females, those who increased their consumption of takeaway foods during the study period were at increased risk for developing depressive symptomatology (b=1.82, 95% CI −0.05 to 3.71). Conclusions There are multiple, probably complex, relationships between diet, physical activity and outcomes of obesity and mental health as well as between the outcomes themselves. Healthier diets and increased physical activity should be foundations for healthier body weight and mental health. Trial registration number ACTRN12615000842561; Results.
Jns Journal of Nutritional Science

Consumption of Buglossoides arvensis seed oil is safe and increases tissue long-chain n-3 fatty acid content more than flax seed oil – results of a phase I randomised clinical trial Abstract Enrichment of tissues with ≥20-carbon n-3 PUFA like EPA is associated with positive cardiovascular outcomes. Stearidonic acid (SDA; 18 : 4n-3) and α-linolenic acid (ALA; 18 : 3n-3) are plant-derived dietary n-3 PUFA; however, direct comparisons of their impact on tissue n-3 PUFA content are lacking. Ahiflower ® oil extracted from Buglossoides arvensis seeds is the richest known non-genetically modified source of dietary SDA. To investigate the safety and efficacy of dietary Ahiflower oil, a parallel-group, randomised, double-blind, comparator-controlled phase I clinical trial was performed. Diets of healthy subjects (n 40) were supplemented for 28 d with 9·1 g/d of Ahiflower (46 % ALA, 20 % SDA) or flax seed oil (59 % ALA). Blood and urine chemistries, blood lipid profiles, hepatic and renal function tests and haematology were measured as safety parameters. The fatty acid composition of fasting plasma, erythrocytes, poly-morphonuclear cells and mononuclear cells were measured at baseline and after 14 and 28 d of supplementation. No clinically significant changes in safety parameters were measured in either group. Tissue ALA and EPA content increased in both groups compared with baseline, but EPA accrual in plasma and in all cell types was greater in the Ahiflower group (time × treatment interactions, P ≤ 0·01). Plasma and mononuclear cell eicosatetraenoic acid (20 : 4n-3) and docosapentaenoic acid (22 : 5n-3) content also increased significantly in the Ahiflower group compared with the flax group. In conclusion, the consumption of Ahiflower oil is safe and is more effective for the enrichment of tissues with 20-and 22-carbon n-3 PUFA than flax seed oil. n-3 PUFA are nutrients that are naturally enriched in common foods such as fatty fish and several plant-derived oils like rapeseed and soyabean oils. Dietary supplements such as fish oils and flax seed oil are also rich sources of n-3 PUFA while other foods including eggs and baked goods that have been supplemented with n-3 PUFA are increasingly available (1). While a review of more recent clinical reports has questioned the health benefits of consuming n-3 PUFA supplements (2) , there is a more extensive literature spanning several decades indicating that dietary n-3 PUFA promote health and prevent disease (3–9). The simplest n-3 PUFA is α-linolenic acid (ALA; 18 …
The α-Helical Content of the Transmembrane Domain of the British Dementia Protein-2 (Bri2) Determines Its Processing by Signal Peptide Peptidase-like 2b (SPPL2b)*

Background: Bri2 is a substrate for intramembrane proteolysis by SPPL2b. Results: Reducing the α-helical content of the Bri2 transmembrane domain increases its intramembrane cleavage by SPPL2b. Destabilization of the Bri2 transmembrane domain is predominantly mediated by Gly-60. Conclusion: A single helix-destabilizing glycine residue of the transmembrane domain of Bri2 is sufficient for efficient intramembrane proteolysis by SPPL2b. Significance: Understanding substrate requirements of intramembrane-cleaving proteases. Regulated intramembrane proteolysis is a widely accepted concept describing the processing of various transmembrane proteins via ectodomain shedding followed by an intramembrane cleavage. The resulting cleavage products can be involved in reverse signaling. Presenilins, which constitute the active center of the γ-secretase complex, signal peptide peptidase (SPP), and its homologues, the SPP-like (SPPL) proteases are members of the family of intramembrane-cleaving aspartyl proteases of the GXGD-type. We recently demonstrated that Bri2 (itm2b) is a substrate for regulated intramembrane proteolysis by SPPL2a and SPPL2b. Intramembrane cleavage of Bri2 is triggered by an initial shedding event catalyzed by A Disintegrin and Metalloprotease 10 (ADAM10). Additionally primary sequence determinants within the intracellular domain, the transmembrane domain and the luminal juxtamembrane domain are required for efficient cleavage of Bri2 by SPPL2b. Using mutagenesis and circular dichroism spectroscopy we now demonstrate that a high α-helical content of the Bri2 transmembrane domain (TMD) reduces cleavage efficiency of Bri2 by SPPL2b, while the presence of a GXXXG dimerization motif influences the intramembrane cleavage only to a minor extent. Surprisingly, only one of the four conserved intramembrane glycine residues significantly affects the secondary structure of the Bri2 TMD and thereby its intramembrane cleavage. Other glycine residues do not influence the α-helical content of the transmembrane domain nor its intramembrane processing.