Miracle-dz/UniFAR-FTUs huggingface dataset:
Stroke prevention by percutaneous closure of patent foramen ovale: a systematic review and meta-analysis

Context The role of percutaneous closure of patent foramen oval (PFO) in patients with cryptogenic stroke has been very controversial for years due to a lack of clear evidence. Objective Systematic review and meta-analysis of the effect of percutaneous PFO closure for secondary prevention of cryptogenic strokes as compared to best medical therapy (BMT). Data sources Trials were identified through a literature search until 28 May 2013. Study selection Controlled clinical trials (randomised and non-randomised) comparing percutaneous PFO closure with BMT. Data extraction and synthesis Main end point of interest was stroke. A random effects model was used to calculate the pooled relative risks (RR) with 95% CIs. Results A total of 14 studies (three randomised controlled trials (RCT) and 11 non-randomised observational studies (non-RCT)), and a total of 4335 patients were included for this analysis. There was no significant treatment effect of PFO closure regarding stroke among the RCT (RR 0.66, 95% CI 0.37 to 1.19, p=0.171). However, among non-RCT stroke was reduced (RR 0.37, 95% CI 0.20 to 0.67, p<0.001) after PFO closure. A time-to-event (stroke) analysis, combining all three RCT and the two non-RCT which applied strict multivariate adjustments, showed a borderline significant risk reduction after PFO closure (HR 0.58, 95% CI 0.33 to 0.99, p=0.047). Neither risk of bleeding nor mortality differed significantly between the groups. However, there was a higher incidence of new onset atrial fibrillation in the closure group (RR 3.50, 95% CI 1.47 to 8.35, p=0.005). Conclusions Percutaneous closure of PFO in patients with cryptogenic stroke does not appear superior to medical therapy according to currently available randomised data. Furthermore, it is associated with an increased incidence of atrial fibrillation. However, there are signals pointing towards a potential benefit and more research should be strongly encouraged.
Phase II study of i.v. interferon‐gamma in Japanese patients with mycosis fungoides

A multisite, open‐label, non‐randomized, single‐arm phase II study was conducted to evaluate the efficacy and safety profiles of interferon‐γ in Japanese patients diagnosed with stage IA–IIIA mycosis fungoides (MF). Interferon‐γ was administrated i.v. to 15 patients at a dose of 2 million Japan reference units once daily over 5 days a week for the first 4 weeks, followed by subsequent intermittent injection. The primary efficacy end‐point was the overall skin response during the study as assessed according to the evaluation criteria for chemotherapeutics for malignant skin carcinomas. Of the 15 patients, 11 (73.3%) achieved the objective response. Of the other four patients, three remained on treatment during study with stable disease and one showed disease progression. The median duration of stable disease was not reached but was 170 days or more (range, 29 to ≥253 days). As assessed according to the modified severity weighted assessment tool, nine patients (60.0%) achieved the objective response. The most common drug‐related adverse event (AE) was influenza‐like illness occurring in all patients enrolled, which did not lead to discontinuation of the study. Two serious AE were reported in two patients: aggravation of MF and aggravation of cataract, neither of which was considered directly related to the study drug. The patient with aggravation of MF died 50 days after the initiation of the study treatment. Another patient was withdrawn from the study due to drug‐related cough, which disappeared after discontinuation of the drug. Overall, interferon‐γ was effective and well‐tolerated in Japanese patients with MF.
Structure-Based Vaccines Provide Protection in a Mouse Model of Ehrlichiosis

Background Recent advances in bioinformatics have made it possible to predict the B cell and T cell epitopes of antigenic proteins. This has led to design of peptide based vaccines that are more specific, safe, and easy to produce. The obligately intracellular gram negative bacteria Ehrlichia cause ehrlichioses in humans and animals. As yet there are no vaccines to protect against Ehrlichia infection. Methodology/Principal Findings We applied the principle of structural vaccinology to design peptides to the epitopes of Ehrlichia muris outer membrane P28-19 (OMP-1/P28) and Ehrlichia Heat shock protein 60 (Hsp60/GroEL) antigenic proteins. Both P28-19 and Ehrlichia Hsp60 peptides reacted with polyclonal antibodies against E. canis and E. chaffeensis and could be used as a diagnostic tool for ehrlichiosis. In addition, we demonstrated that mice vaccinated with Ehrlichia P28-19 and Hsp60 peptides and later challenged with E. muris were protected against the pathogen. Conclusions/Significance Our results demonstrate the power of structural vaccines and could be a new strategy in the development of vaccines to provide protection against pathogenic microorganisms.
Are HIV Smartphone Apps and Online Interventions Fit for Purpose?

Sexual health is an under-explored area of Human-Computer Interaction (HCI), particularly sexually transmitted infections such as HIV. Due to the stigma associated with these infections, people are often motivated to seek information online. With the rise of smartphone and web apps, there is enormous potential for technology to provide easily accessible information and resources. However, using online information raises important concerns about the trustworthiness of these resources and whether they are fit for purpose. We conducted a review of smartphone and web apps to investigate the landscape of currently available online apps and whether they meet the diverse needs of people seeking information on HIV online. Our functionality review revealed that existing technology interventions have a one-size-fits-all approach and do not support the breadth and complexity of HIV-related support needs. We argue that technology-based interventions need to signpost their offering and provide tailored support for different stages of HIV, including prevention, testing, diagnosis and management.
Letter-based speech synthesis

Initial attempts at performing text-to-speech conversion based on standard orthographic units are presented, forming part of a larger scheme of training TTS systems on features that can be trivially extracted from text. We evaluate the possibility of using the technique of decision-tree-based context clustering conventionally used in HMM-based systems for parametertying to handle letter-to-sound conversion. We present the applicationofamethodofcompound-featurediscoverytocorpusbased speech synthesis. Finally, an evaluation of intelligibility of letter-based systems and more conventional phoneme-based systems is presented. Index Terms : Statistical parametric speech synthesis, HMMbased speech synthesis, letter-to-sound conversion, graphemes.
Reactive oxygen species , but not Ca 2 overloading , trigger pH-and mitochondrial permeability transition-dependent death of adult rat myocytes after ischemia-reperfusion

Kim, Jae-Sung, Yingai Jin, and John J. Lemasters. Reactive oxygen species, but not Ca overloading, trigger pHand mitochondrial permeability transition-dependent death of adult rat myocytes after ischemia-reperfusion. Am J Physiol Heart Circ Physiol 290: H2024 –H2034, 2006. First published January 6, 2006; doi:10.1152/ajpheart.00683. 2005. —We investigated the role of pH, reactive oxygen species (ROS), Ca , and the mitochondrial permeability transition (MPT) in pH-dependent ischemia-reperfusion injury to adult rat myocytes. Myocytes were incubated in anoxic Krebs-Ringer-HEPES buffer at pH 6.2 for 3 h to simulate ischemia. To simulate reperfusion, myocytes were reoxygenated at pH 6.2 or 7.4 for 2 h. Some myocytes were treated with MPT blockers (cyclosporin A and N-methyl-4-isoleucine cyclosporin) and antioxidants (desferal, diphenylphenylene diamine, and 2-mercaptopropionyl glycine). Mitochondrial membrane potential, inner membrane permeabilization, and ROS formation were imaged with tetramethylrhodamine methyl ester, calcein, and chloromethyldichlorofluorescein diacetate, respectively. For Ca imaging, myocytes were coloaded with rhod-2 and fluo-4 to evaluate mitochondrial and cytosolic Ca , respectively. After 10 min of reperfusion at pH 7.4, calcein redistributed across the mitochondrial inner membrane, an event preceded by mitochondrial ROS formation and accompanied by hypercontracture, mitochondrial depolarization, and then cell death. Acidotic reperfusion, antioxidants, and MPT blockers each prevented the MPT, depolarization, hypercontraction, and cell killing. Antioxidants, but neither MPT blockers nor acidotic reperfusion, inhibited ROS formation after reperfusion. Furthermore, anoxic reperfusion at pH 7.4 prevented cell death. Both mitochondrial and cytosolic Ca increased during ischemia but recovered in the first minutes of reperfusion. Mitochondrial and cytosolic Ca overloading again occurred late after reperfusion. This late Ca overloading was blocked by MPT inhibition. Intramitochondrial Ca chelation by cold loading/warm incubation of BAPTA did not prevent cell death after reperfusion. In conclusion, mitochondrial ROS, together with normalization of pH, promote MPT onset and subsequent myocyte death after reperfusion. In contrast, Ca overloading appears to be the consequence of bioenergetic failure after the MPT and is not a factor promoting MPT onset.
S100A8/A9 (Calprotectin) Negatively Regulates G2/M Cell Cycle Progression and Growth of Squamous Cell Carcinoma

Malignant transformation results in abnormal cell cycle regulation and uncontrolled growth in head and neck squamous cell carcinoma (HNSCC) and other cancers. S100A8/A9 (calprotectin) is a calcium-binding heterodimeric protein complex implicated in cell cycle regulation, but the specific mechanism and role in cell cycle control and carcinoma growth are not well understood. In HNSCC, S100A8/A9 is downregulated at both mRNA and protein levels. We now report that downregulation of S100A8/A9 correlates strongly with a loss of cell cycle control and increased growth of carcinoma cells. To show its role in carcinogenesis in an in vitro model, S100A8/A9 was stably expressed in an S100A8/A9-negative human carcinoma cell line (KB cells, HeLa-like). S100A8/A9 expression increases PP2A phosphatase activity and p-Chk1 (Ser345) phosphorylation, which appears to signal inhibitory phosphorylation of mitotic p-Cdc25C (Ser216) and p-Cdc2 (Thr14/Tyr15) to inactivate the G2/M Cdc2/cyclin B1 complex. Cyclin B1 expression then downregulates and the cell cycle arrests at the G2/M checkpoint, reducing cell division. As expected, S100A8/A9-expressing cells show both decreased anchorage-dependent and -independent growth and mitotic progression. Using shRNA, silencing of S100A8/A9 expression in the TR146 human HNSCC cell line increases growth and survival and reduces Cdc2 inhibitory phosphorylation at Thr14/Tyr15. The level of S100A8/A9 endogenous expression correlates strongly with the reduced p-Cdc2 (Thr14/Tyr14) level in HNSCC cell lines, SCC-58, OSCC-3 and UMSCC-17B. S100A8/A9-mediated control of the G2/M cell cycle checkpoint is, therefore, a likely suppressive mechanism in human squamous cell carcinomas and may suggest new therapeutic approaches.
Formation of perineuronal nets in organotypic mouse brain slice cultures is independent of neuronal glutamatergic activity

Perineuronal nets (PNs) are a specialized form of the extracellular matrix and cover specific sets of neurons in distinct brain areas. Animal experiments on sensory visual deprivation have demonstrated that the generation of PNs around neurons of the visual cortex is dependent on neuronal activity during the critical period of visual experience. The importance of the activity of specific neurotransmitter systems for PN formation has, however, not yet been demonstrated. Based on the predominantly glutamatergic innervation of the visual cortex we hypothesized that reduced glutamatergic activity impairs the development of PNs. To address this question, genetic mouse models with compromised glutamate release [Munc13‐1‐knockout (KO) and Munc13‐1/2 double‐KO (DKO)] and chronic pharmacological treatments interfering with specific steps of glutamatergic transmission were used. Under experimental conditions of glutamatergic hypofunction PN formation was studied in organotypic brain slice cultures with Wisteria floribunda lectin binding and with aggrecan immunohistochemistry. After cultivation for 21 days a regular PN formation was observed in brain slices (i) derived from Munc13‐1‐KO and Munc13‐1/2‐DKO mice, (ii) after blockade of metabotropic and ionotropic glutamate receptors with MCPG and kynurenate, and (iii) after suppression of glutamate release by blockade of presynaptic Ca++ channels with riluzole. Nonselective suppression of neuronal activity by blockade of voltage‐gated sodium channels with tetrodotoxin clearly inhibited PN formation. These results indicate that neuronal activity is required but that the glutamatergic system is not essential for PN development.
Ultralow Reflectivity Spiral Phase Plate for Generation of Millimeter-wave OAM Beam

An ultralow reflectivity spiral phase plate (SPP) is proposed to generate an orbital angular momentum (OAM) beam at millimeter-wave frequency. The SPP is composed of unit cells whose equivalent permittivity and thickness are designed to satisfy the impedance matching condition based on transmission line theory. The designed SPP is fabricated by a 3D printing technique. The near-field and far-field phase distributions clearly exhibit the azimuth phase shifting, and the far field directivity pattern shows that the direction, gain, and 3-dB beam-width of the main lobe are about 10.5°, 14.6 dB, and 14.5°, respectively. Compared with no impedance-matched SPP, the reflectivity of the SPP is improved by more than 20 dB.
Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke.

BACKGROUND Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely used for the treatment of hypercholesterolemia and coronary heart disease and for the prevention of stroke. There have been various adverse effects, most commonly affecting muscle and ranging from myalgia to rhabdomyolysis. These adverse effects may be due to a coenzyme Q(10) (CoQ(10)) deficiency because inhibition of cholesterol biosynthesis also inhibits the synthesis of CoQ(10). OBJECTIVE To measure CoQ(10) levels in blood from hypercholesterolemic subjects before and after exposure to atorvastatin calcium, 80 mg/d, for 14 and 30 days. DESIGN Prospective blinded study of the effects of short-term exposure to atorvastatin on blood levels of CoQ(10). SETTING Stroke center at an academic tertiary care hospital. Patients We examined a cohort of 34 subjects eligible for statin treatment according to National Cholesterol Education Program: Adult Treatment Panel III criteria. RESULTS The mean +/- SD blood concentration of CoQ(10) was 1.26 +/- 0.47 micro g/mL at baseline, and decreased to 0.62 +/- 0.39 micro g/mL after 30 days of atorvastatin therapy (P<.001). A significant decrease was already detectable after 14 days of treatment (P<.001). CONCLUSIONS Even brief exposure to atorvastatin causes a marked decrease in blood CoQ(10) concentration. Widespread inhibition of CoQ(10) synthesis could explain the most commonly reported adverse effects of statins, especially exercise intolerance, myalgia, and myoglobinuria.
Simple Tests for Models of Dependence between Multiple Financial Time Series, with Applications to U.S. Equity Returns and Exchange Rates

Evidence that asset returns are more highly correlated during volatile markets and during market downturns (see Longin and Solnik, 2001, and Ang and Chen, 2002) has lead some researchers to propose alternative models of dependence. In this paper we develop two simple goodness-of-fit tests for such models. We use these tests to determine whether the multivariate Normal or the Student’s t copula models are compatible with U.S. equity return and exchange rate data. Both tests are robust to specifications of marginal distributions, and are based on the multivariate probability integral transform and kernel density estimation. The first test is consistent but requires the estimation of a multivariate density function and is recommended for testing the dependence structure between a small number of assets. The second test may not be consistent against all alternatives but it requires kernel estimation of only a univariate density function, and hence is useful for testing the dependence structure between a large number of assets. We justify our tests for both observable multivariate strictly stationary time series and for standardized innovations of GARCH models. A simulation study demonstrates the efficacy of both tests. When applied to equity return data and exchange rate return data, we find strong evidence against the normal copula, but little evidence against the more flexible Student’s t copula.
Advanced topics in control systems theory : lecture notes from FAP 2004

Nonlinear Adaptive Stabilization via System Immersion: Control Design and Applications Cascaded Nonlinear Time-varying Systems: Analysis and Design Control of Mechanical Systems from Aerospace Engineering Compositional Modelling of Distributed-parameter Systems Algebraic Analysis of Control Systems Defined by Partial Differential Equations Structural Properties of Discrete and Continuous Linear Time-varying Systems: A Unified Approach.
Estimates of Body Fat in Children by Hologic QDR-2000 and QDR-4500A Dual-Energy X-ray Absorptiometers Compared With Deuterium Dilution

ABSTRACT We evaluated the accuracy with which the Hologic QDR-4500A and QDR-2000 densitometers measure fat mass (FM) in 95 children. FM was derived from total body water measured by deuterium dilution (DD) in all children, by QDR-4500A in 50, and by QDR-2000 in 45 children. Compared with DD, both instruments underestimated FM (QDR-4500A: 3.35 ± 2.5 kg, P < 0.0001; QDR-2000: 1.05 ± 1.5 kg, P < 0.0001). Both absorptiometers showed magnitude biases relative to DD (QDR-4500: r = +0.70, P < 0.001; QDR-2000: r = −0.51, P < 0.001). We conclude that neither densitometer is equivalent to DD for estimation of children's FM. The QDR-4500A's current calibration seems to provide an even greater underestimate of FM than the QDR-2000.
On the Use of Requirements for Driving Call-for-Tender Processes for Procuring Coarse-grained OTS Components

Because of their complexity, software systems are currently built by integrating components of different nature into hybrid architectures, usually including some third party Off-The-Shelf (OTS) components. Several methods have been proposed to support OTS component selection. Most of them work by comparing requirements, incrementally gained though several iterations, and component descriptions. However, the iterative nature of these methods makes them practically unsuitable in some cases, particularly when conducting call-for-tender-based processes for selecting coarse-grained OTS components. In these cases, company goals need to be thoughtfully and systematically engineered to obtain a well structured set of requirements, which is to remain static during the entire procurement process and cannot be validated through hands-on experimentation. In this paper we report a case study in the selection of an ERP system for a telecommunications company using a call-for-tender process. We present the activities that were undertaken to elicit, analyze and structure the requirements to be included in call-for-tender documents, and the evaluation of components based on the identification of mismatches between requirements and component capabilities.
Investigation of Congenital Myasthenia Reveals Functional Asymmetry of Invariant Acetylcholine Receptor (AChR) Cys-loop Aspartates*

We identify two heteroallelic mutations in the acetylcholine receptor δ-subunit from a patient with severe myasthenic symptoms since birth: a novel δD140N mutation in the signature Cys-loop and a mutation in intron 7 of the δ-subunit gene that disrupts splicing of exon 8. The mutated Asp residue, which determines the disease phenotype, is conserved in all eukaryotic members of the Cys-loop receptor superfamily. Studies of the mutant acetylcholine receptor expressed in HEK 293 cells reveal that δD140N attenuates cell surface expression and apparent channel gating, predicting a reduced magnitude and an accelerated decay of the synaptic response, thus reducing the safety margin for neuromuscular transmission. Substituting Asn for Asp at equivalent positions in the α-, β-, and ϵ-subunits also suppresses apparent channel gating, but the suppression is much greater in the α-subunit. Mutant cycle analysis applied to single and pairwise mutations reveals that αAsp-138 is energetically coupled to αArg-209 in the neighboring pre-M1 domain. Our findings suggest that the conserved αAsp-138 and αArg-209 contribute to a principal pathway that functionally links the ligand binding and pore domains.
Abstraction Based Reachability Analysis for Finite Branching Stochastic Hybrid Systems

In this paper, we address the problem of computing the probability of reaching a desired set in a subclass of stochastic hybrid systems, wherein the stochasticity arises from the randomness of the initial distribution of continuous states, and the probabilistic transitions in the underlying finite state Markov chain. In particular, the continuous dynamics is deterministic for each mode and hence, there are finitely many probabilistic successors for a given state. We exploit this property and extend a partition based abstraction technique developed for finite state systems to the stochastic hybrid system setting. We prove the correctness of our algorithm by defining appropriate simulation relations that relate the stochastic hybrid system to a finite state ``generalized" probabilistic transition system that we obtain as a result of abstraction. We show that the simulation relation defined provides upper and lower bounds on the probability of reachability. In particular, tighter bounds can be obtained by refining the partition. We apply our algorithm to automatically analyze a smart home application.
Postoperative Headache after Undergoing Acoustic Neuroma Surgery via the Retrosigmoid Approach

To estimate the duration of postoperative headache after surgery for acoustic neuroma and the effects of age, sex, tumor size, extent of tumor resection, type of skin incision, surgical duration, hearing preservation, and postoperative facial nerve palsy. This retrospective review analyzed clinical data from 97 patients who had undergone surgery for unilateral acoustic neuroma via the retrosigmoid approach >1 year previously. We investigated whether patients had headache at hospital discharge and during attendance at outpatient clinics. We classified postoperative headache as grade 0 (no headache), 1 (tolerable headache without medication), or 2 (headache requiring medication). The period of headache was defined as the interval in days between surgery and achievement of grade 0. The period of medication for headache was defined as the interval in days between surgery and achievement of grade 0 or 1. Kaplan-Meier analysis revealed median durations of medication and headache of 81 and 641 days, respectively. Headache was cured significantly earlier in patients who underwent surgery using a C-type skin incision (P < 0.001). Headache persisted significantly longer among patients who underwent a shorter surgical procedure (P < 0.02). Multivariate analysis confirmed the type of skin incision as a factor independently associated with duration of postoperative headache. Postoperative headache was cured in the majority of patients within about 2 years after surgery. The C-type skin incision is likely beneficial for reducing the duration of postoperative headache, although headache persisted in a small number of patients.