Miracle-dz/UniFAR-FTUs huggingface dataset:
Remote ischaemic conditioning reduces infarct size in animal in vivo models of ischaemia-reperfusion injury: a systematic review and meta-analysis

Aims The potential of remote ischaemic conditioning (RIC) to ameliorate myocardial ischaemia-reperfusion injury (IRI) remains controversial. We aimed to analyse the pre-clinical evidence base to ascertain the overall effect and variability of RIC in animal in vivo models of myocardial IRI. Furthermore, we aimed to investigate the impact of different study protocols on the protective utility of RIC in animal models and identify gaps in our understanding of this promising therapeutic strategy. Methods and results Our primary outcome measure was the difference in mean infarct size between RIC and control groups in in vivo models of myocardial IRI. A systematic review returned 31 reports, from which we made 22 controlled comparisons of remote ischaemic preconditioning (RIPreC) and 21 of remote ischaemic perconditioning and postconditioning (RIPerC/RIPostC) in a pooled random-effects meta-analysis. In total, our analysis includes data from 280 control animals and 373 animals subject to RIC. Overall, RIPreC reduced infarct size as a percentage of area at risk by 22.8% (95% CI 18.8–26.9%), when compared with untreated controls (P < 0.001). Similarly, RIPerC/RIPostC reduced infarct size by 22.2% (95% CI 17.1–25.3%; P < 0.001). Interestingly, we observed significant heterogeneity in effect size (T2 = 92.9% and I2 = 99.4%; P < 0.001) that could not be explained by any of the experimental variables analysed by meta-regression. However, few reports have systematically characterized RIC protocols, and few of the included in vivo studies satisfactorily met study quality requirements, particularly with respect to blinding and randomization. Conclusions RIC significantly reduces infarct size in in vivo models of myocardial IRI. Heterogeneity between studies could not be explained by the experimental variables tested, but studies are limited in number and lack consistency in quality and study design. There is therefore a clear need for more well-performed in vivo studies with particular emphasis on detailed characterization of RIC protocols and investigating the potential impact of gender. Finally, more studies investigating the potential benefit of RIC in larger species are required before translation to humans.
THE BRIGHTEST CLUSTER GALAXY IN A85: THE LARGEST CORE KNOWN SO FAR

We have found that the brightest cluster galaxy (BCG) in A85, Holm 15A, displays the largest core known so far. Its cusp radius, rγ = 4.57 ± 0.06 kpc (4.″26 ± 0.″06), is more than 18 times larger than the mean for BCGs and ≳ 1 kpc larger than A2261-BCG, hitherto the largest-cored BCG. Holm 15A hosts the luminous amorphous radio source 0039-095B and has the optical signature of a LINER. Scaling laws indicate that this core could host a supermassive black hole (SMBH) of mass M• ∼ (109–1011) M☉. We suggest that cores this large represent a relatively short phase in the evolution of BCGs, whereas the masses of their associated SBMH might be set by initial conditions.
Taxol Directly Induces Endoplasmic Reticulum‐Associated Calcium Changes That Promote Apoptosis in Breast Cancer Cells

Abstract: Calcium, a key regulator of cell survival, is also important in regulating apoptosis. Although the chemotherapeutic agent Taxol employs apoptosis to induce cell death, the exact mechanism of how it induces apoptosis and the role of calcium in this process remains unclear. The main intracellular calcium storehouse, the endoplasmic reticulum, was identified as a new important gateway in apoptosis, possibly providing a target for Taxol. The goal of this study was to investigate whether calcium changes associated with the endoplasmic reticulum, were directly or indirectly generated by Taxol at clinically relevant doses, and related to Taxol‐induced apoptosis in breast cancer cells. Time‐lapsed imaging techniques followed by an endoplasmic reticulum‐targeted construct, cameleon D1ER, were used to monitor cytosol––endoplasmic reticulum calcium dynamics in MDA‐MB‐468 (Bcl‐2 negative) and MCF 7 (Bcl‐2 positive) breast carcinoma cells. Apoptosis levels were measured with Annexin V and Propidium Iodide (PI) using flow cytometry. In both cell lines, Taxol at 2.5 μM (∼10−6 M) was observed to induce significant internal calcium changes, first a rapid endoplasmic reticulum calcium release and a transient cytosolic calcium increase upon Taxol addition. After several hours of Taxol treatment, the endoplasmic reticulum calcium store was gradually depleted, and a sustained cytosolic calcium elevation was observed before significant induction of apoptosis. Inhibition of these calcium changes decreased Taxol‐induced apoptosis levels. In contrast, 0.2 μM Taxol (∼10−7 M) induced only a slight cellular calcium change, not enough to regulate apoptosis. Our findings demonstrate that endoplasmic reticulum calcium stores provide a direct target for Taxol action and are important for induction of apoptosis, independent of Bcl‐2 status. Furthermore, our results show for the first time, that the role of calcium in Taxol‐induced endoplasmic reticulum‐mediated apoptosis is dependent on Taxol dosage.
Adenosine‐Sensitive Ventricular Tachycardia Clinical Characteristics and Response to Catheter Ablation

BackgroundSustained ventricular tachycardia in the absence of structural heart disease may have diverse mechanisms. Termination of the tachycardia by adenosine suggests triggered automaticity as the etiology in many of these patients. We examined the clinical characteristics, electrophysiological responses, and results of catheter ablation in this patient subgroup. Methods and ResultsIntravenous adenosine terminated sustained ventricular tachycardia in seven of 14 consecutive patients without evidence of structural heart disease. In each of these patients, the tachycardia had a left bundle branch block, inferior-axis QRS configuration and occurred predominantly during stress or exertion. A morphologically similar sustained tachycardia was induced in six of seven patients during programmed ventricular stimulation, although day-to-day reproducibility was poor. Signalaveraged ECGs were normal in all patients. Imaging with 123I-metaiodobenzylguanidine did not reveal focal abnormalities in any of five patients. A discrete site of origin was identified in the free wall of the pulmonary infundibulum in all patients. Limited application of direct current shocks (two patients) or radiofrequency energy (five patients) resulted in long-term abolition of spontaneous and inducible ventricular tachycardia in all patients. ConclusionsAdenosine-sensitive ventricular tachycardia appears to arise from relatively discrete sites predominantly located in the free wall of the pulmonary infundibulum. The localized nature of this tachycardia renders it amenable to long-term cure by catheter ablation techniques.
NMDA and Glutamate Evoke Excitotoxicity at Distinct Cellular Locations in Rat Cortical Neurons In Vitro

The development of cortical neurons in vivo andin vitro is accompanied by alterations in NMDA receptor subunit expression and concomitant modifications in the pharmacological profile of NMDA-activated ionic currents. For example, we observed that with decreasing NR2B/NR2A subunit expression ratio, the block of NMDA receptor-mediated whole-cell responses by the NR2B-selective antagonist haloperidol was also decreased. In mature cultures (>22 d in vitro), however, NMDA responses obtained from excised nucleated macropatches, which comprised a large portion of the soma, remained strongly antagonized by haloperidol. These results suggest that in more mature neurons NR1/NR2B receptors appear to be preferentially expressed in the cell body. As predicted from the whole-cell recording pharmacological profile, NMDA-induced toxicity was largely unaffected by haloperidol in mature cultures. However, haloperidol effectively blocked glutamate toxicity in the same cultures, suggesting that the neurotoxic actions of this amino acid were mostly due to the activation of somatic NMDA receptors. In experiments in which the potency of glutamate toxicity was increased by the transport inhibitorl-trans-pyrrolidine-2,4-dicarboxylic acid, the neuroprotective effects of haloperidol were significantly diminished. This was likely because of the fact that glutamate, now toxic at much lower concentrations, was able to reach and activate dendritic receptors under these conditions. These results strongly argue that exogenous glutamate and NMDA normally induce excitotoxicity at distinct cellular locations in mature mixed neuronal cultures and that NR1/NR2B receptors remain an important component in the expression of glutamate, but not NMDA-induced excitotoxicity.
Épuration par cultures fixées sur support géotextile

Les travaux presentes relatent la mise au point d'un procede d'epuration aerobie en lit immerge par bacteries fixees sur support geotextile. Ce materiau facilite la realisation et l'exploitation des installations par rapport aux lits immerges granulaires. La bibliographie et les experiences preliminaires menees sur differents geotextiles demontrent que les criteres de choix pour les materiaux de fixation sont indissociables de leur mise en œuvre. Pour la suite de cette etude le geotextile ENKAMAT est utilise. La colonisation du support selectionne est realisee dans un pilote industriel a l'interieur duquel le materiau est dispose en nappes. La methodologie du suivi consiste a faire varier la charge polluante en agissant sur le debit d'eau et le dopage de l'effluent, voire les deux. Les performances du procede sont etudiees en mesurant regulierement les parametres classiques de pollution. Les caracteristiques hydrauliques du lit se deduisent de la distribution du temps de sejour, evaluee par tracage. La chromatographie en phase gazeuse permet de quantifier le transfert de l'oxygene. Le procede fonctionne par cycles de 2 a 12 jours entrecoupes de lavages air-eau. La capacite maximale, mesuree en charge volumique appliquee, est d'environ 7 kg DCO/m3/j pour une duree de fonctionnement de 3-4 jours, satisfaisant le niveau de rejet e (norme francaise : MES 30 mg/1, DBO5 30 mg/1, DCO 90 mg/1). La modelisation des phenomenes de l'epuration revele que : - la cinetique d'elimination du substrat organique est d'ordre 1, - la charge particulaire de l'eau epuree depend a la fois du decrochage du biofilm, fonction de la vitesse de l'eau, et de la croissance des bacteries libres, - la duree du cycle est liee a l'accumulation de la biomasse fixee, - et que la diffusion du substrat organique controle l'epuration. De plus, cette modelisation a permis l'elaboration d'abaques de dimensionnement de lit immerge sur geotextile.
Goals of New Long-Stay Patients in Supported Housing: A UK Study

Aim: This study assessed the goals ‘new’ long-stay clients aim to achieve by being in supported housing (SH), compared the goals stated by clients and staff, and tested whether subgroups of clients can be identified on the basis of their goals, quality of life and psychopathology. Method: Interviews were conducted with 41 clients and 39 staff of supported houses in London and Essex, UK. Descriptive, content and cluster analyses were used to analyse the results. Results: Clients’ most frequently reported goal was moving to independent housing, followed by staying healthy, and increasing living skills. A comparison of goals reported by clients and staff showed poor or no agreement between them. Cluster analyses identified two clusters of clients. Cluster A (n 1/4 23) contained those with no stated goals (or with the aim of staying healthy), lower quality of life, and more psychopathology; cluster B (n 1/4 18) included those with an aim to move to independent housing, better quality of life, and less psychopathology. Conclusion: In the UK, more staff training may be needed to identify and achieve the goals of the ‘new’ long-stay clients. For a subgroup of these clients, SH may still be a long-term care setting; while for another subgroup, new forms of rehabilitation in SH and better opportunities to leave SH may have to be developed. More conceptual and practical efforts are needed to manage the transformation of many settings from homes for life to transitional places where residents receive specific interventions.
Rationale and design of the PRognostic Importance of MIcrovascular Dysfunction in asymptomatic patients with Aortic Stenosis (PRIMID-AS): a multicentre observational study with blinded investigations

Introduction Aortic stenosis (AS) is the commonest valve disorder in the developed world requiring surgery. Surgery in patients with severe asymptomatic AS remains controversial. Exercise testing can identify asymptomatic patients at increased risk of death and symptom development, but with limited specificity, especially in older adults. Cardiac MRI (CMR), including myocardial perfusion reserve (MPR) may be a novel imaging biomarker in AS. Aims (1) To improve risk stratification in asymptomatic patients with AS and (2) to determine whether MPR is a better predictor of outcome than exercise testing and brain natriuretic peptide (BNP). Method/design Multicentre, prospective observational study in the UK, comparing MPR with exercise testing and BNP (with blinded CMR analysis) for predicting outcome. Population 170 asymptomatic patients with moderate-to-severe AS, who would be considered for aortic valve replacement (AVR). Primary outcome Composite of: typical symptoms necessitating referral for AVR and major adverse cardiovascular events. Follow-up: 12–30 months (minimum 12 months). Primary hypothesis MPR will be a better predictor of outcome than exercise testing and BNP. Ethics/dissemination The study has full ethical approval and is actively recruiting patients. Data collection will be completed in November 2014 and the study results will be submitted for publication within 6 months of completion. ClinicalTrials.gov identifier NCT01658345.
No Relationship of Lipid-Lowering Agents to Hematoma Growth: Pooled Analysis of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials Studies

Background and Purpose— Controversy persists over statins and risk of intracerebral hemorrhage. We determined associations of premorbid lipid-lowering therapy and outcomes among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT). Methods— The pooled data of INTERACT 1 and 2 (international, multicenter, prospective, open, blinded end point, randomized controlled trials of patients with intracerebral hemorrhage [<6 hours] and elevated systolic blood pressure) were analyzed with regard to associations of baseline lipid-lowering treatment and clinical outcomes of 3184 participants in a multivariate model. Associations of lipid-lowering therapy and hematoma growth (baseline to 24 hours) in computed tomographic substudies participants (n=1310) were estimated in ANCOVA. Results— Among 204 patients (6.5%) with baseline lipid-lowering treatment, 90-day clinical outcomes were not significantly different after adjustment for confounding variables including region and age. In the computed tomographic substudy, 24-hour hematoma growth was greater in 124 patients (9%) with, compared with those without, prior lipid-lowering therapy. However, this association was not significant between groups (9.2 versus 6.8 mL; P<0.13), after adjustment for prior antithrombotic therapy. Conclusions— No independent associations were found between lipid-lowering medication and adverse outcomes in patients with intracerebral hemorrhage. Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT00226096 and NCT00716079.
Translated Poisson approximation using exchangeable pair couplings.

It is shown that the method of exchangeable pairs introduced by Stein [Approximate Computation of Expectations (1986) IMS, Hayward, CA] for normal approximation can effectively be used for translated Poisson approximation. Introducing an additional smoothness condition, one can obtain approximation results in total variation and also in a local limit metric. The result is applied, in particular, to the anti-voter model on finite graphs as analyzed by Rinott and Rotar [Ann. Appl. Probab. 7 (1997) 1080–1105], obtaining the same rate of convergence, but now for a stronger metric.
USENIX Association Proceedings of FAST ’ 03 : 2 nd USENIX Conference on File and Storage Technologies

Versioning file systems retain earlier versions of modified files, allowing recovery from user mistakes or system corruption. Unfortunately, conventional versioning systems do not efficiently record large numbers of versions. In particular, versioned metadata can consume as much space as versioned data. This paper examines two space-efficient metadata structures for versioning file systems and describes their integration into the Comprehensive Versioning File System (CVFS), which keeps all versions of all files. Journal-based metadata encodes each metadata version into a single journal entry; CVFS uses this structure for inodes and indirect blocks, reducing the associated space requirements by 80%. Multiversion b-trees extend each entry’s key with a timestamp and keep current and historical entries in a single tree; CVFS uses this structure for directories, reducing the associated space requirements by 99%. Similar space reductions are predicted via trace analysis for other versioning strategies (e.g., on-close versioning). Experiments with CVFS verify that its current-version performance is similar to that of non-versioning file systems while reducing overall space needed for history data by a factor of two. Although access to historical versions is slower than conventional versioning systems, checkpointing is shown to mitigate and bound this effect.
Growth Factor Activity of Endothelin-1 in Primary Astrocytes Mediated by Adhesion-Dependent and -Independent Pathways

Endothelin-1 (ET-1) has been shown to induce DNA synthesis in primary astrocytes by stimulating the extracellular signal-regulated kinase (ERK) pathway. To clarify the mechanisms responsible for the anchorage-dependent growth of astrocytes, the relationships between cell adhesion and ERK activation were investigated. Here it is reported that ET-1 promotes the formation of stress fibers and focal adhesions and the tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin, as well as Src activation and association of phosphorylated FAK with Grb2. Pretreatment of astrocytes with cytochalasin D or C3-transferase, which inhibits actin polymerization or Rho activity, respectively, prevented the activation/phosphorylation of Src, FAK, and paxillin after ET-1 stimulation; by contrast, the ERK pathway was not significantly affected. This differential activation of FAK/Src and ERK pathways was also observed with astrocytes 10 and 60 min after replating on poly-l-ornithine-precoated dishes. Collectively, these findings indicate that activation of FAK and Src is dependent on actin cytoskeleton integrity, Rho activation, and adhesion to extracellular matrix, whereas ERK activation is independent of these intracellular events and seems to correlate with activation of the newly identified protein tyrosine kinase PYK2. Induction of DNA synthesis by ET-1, however, was reduced dramatically in astrocytes pretreated with either cytochalasin D or C3-transferase. This study provides a demonstration of Rho- and adhesion-dependent activation of FAK/Src, which collaborates with adhesion-independent activation of PYK2/ERK for DNA synthesis in ET-1-stimulated astrocytes.
Analyzing and characterizing small-world graphs

We study variants of Kleinberg's small-world model where we start with a <i>k</i>-dimensional grid and add a random directed edge from each node. The probability <i>u's</i> random edge is to <i>v</i> is proportional to <i>d(u,v)<sup>-r</sup></i> where <i>d(u,v)</i> is the lattice distance and <i>r</i> is a parameter of the model.For a <i>k</i>-dimensional grid, we show that these graphs have poly-log expected diameter when <i>k</i> < <i>r</i> < 2<i>k</i>, but have polynomial expected diameter when <i>r</i> > 2<i>k. </i> This shows an interesting phase-transition between small-world and "large-world" graphs.We also present a general framework to construct classes of small-world graphs with Θ(log <i>n</i>) expected diameter, which includes several existing settings such as Kleinberg's grid-based and tree-based settings [15]. We also generalize the idea of 'adding links with probability α the inverse distance' to design small-world graphs. We use semi-metric and metric functions to abstract distance to create a class of random graphs where almost all pairs of nodes are connected by a path of length <i>O</i> (log <i>n</i>), and using only local information we can find paths of poly-log length.
Migration and Differentiation of Autoreactive B-1 Cells Induced by Activated γ/δ T Cells in Antierythrocyte Immunoglobulin Transgenic Mice

Using normal and transgenic (Tg) mice, we have shown that peritoneal B-1 cells are activated by administration of cytokines or lipopolysaccharide and migrate to other lymphoid organs where they differentiate into antibody-secreting cells. However, little is known about the process of B-1 cell migration and differentiation in vivo. We developed a mouse line by crossing the antierythrocyte antibody Tg mice (HL mice) with TCR-γ/δ Tg mice specific for a self-thymus leukemia (TL) antigen in the recombination activating gene (RAG)2−/− background. In the presence of the self-antigen, Tg γ/δ T cells increased in number and manifested activated phenotypes. Peritoneal B-1 cells in these mice migrated into mesenteric lymph nodes and differentiated into autoantibody-secreting cells, resulting in strong autoimmune hemolytic anemia. Furthermore, transfer of RAG2−/− × HL bone marrow or peritoneal cells into the peritoneal cavity of RAG2−/− × TCR-γ/δ Tg mice gave rise to donor-derived B-1 cells in mesenteric lymph nodes, and these cells produced the autoantibody. Thus, this study demonstrates that the migration of B-1 cells and differentiation into the antibody-secreting cells can be induced by noncognate T cell help and implies the possibility that γ/δ T cells may induce B-1 cell differentiation in vivo.
Average of delta: a new quality control tool for clinical laboratories

Background Average of normals is a tool used to control assay performance using the average of a series of results from patients’ samples. Delta checking is a process of identifying errors in individual patient results by reviewing the difference from previous results of the same patient. This paper introduces a novel alternate approach, average of delta, which combines these concepts to use the average of a number of sequential delta values to identify changes in assay performance. Methods Models for average of delta and average of normals were developed in a spreadsheet application. The model assessed the expected scatter of average of delta and average of normals functions and the effect of assay bias for different values of analytical imprecision and within- and between-subject biological variation and the number of samples included in the calculations. The final assessment was the number of patients’ samples required to identify an added bias with 90% certainty. Results The model demonstrated that with larger numbers of delta values, the average of delta function was tighter (lower coefficient of variation). The optimal number of samples for bias detection with average of delta was likely to be between 5 and 20 for most settings and that average of delta outperformed average of normals when the within-subject biological variation was small relative to the between-subject variation. Conclusions Average of delta provides a possible additional assay quality control tool which theoretical modelling predicts may be more valuable than average of normals for analytes where the group biological variation is wide compared with within-subject variation and where there is a high rate of repeat testing in the laboratory patient population.