gebhart/patrepeval huggingface dataset:
[Beta blockers in heart failure therapy with special reference to the COPERNICUS Study]. (2002)

During the past 15 years, the pathophysiological concept of heart failure as a neurohormonal disease has influenced heart failure therapy substantially. ACE-inhibitors have become the mainstay of heart failure therapy. In addition, beta blocker evolved to be effective in improving survival in this disease. Recently, the COPERNICUS study established the efficacy of carvedilol in severe heart failure and extended the benefits of this drug first observed in patients with mild and moderate symptoms to those with advanced disease. In this study, carvedilol resulted in a significant reduction of all-cause mortality and combined mortality and hospitalization, the frequency of hospitalizations, the risk of repeated hospitalizations, the number of days in hospital, the average duration of each admission and the utilization of treatments and procedures for heart failure. Carvedilol was well tolerated, improved the sense of well-being, was associated with a lower risk of a serious adverse event, particularly one related to the progression of heart failure and fewer patients requiring withdrawal of treatment for an adverse event. These favourable results were equally seen in all subgroups. Carvedilol treatment was even cost-effective in severe disease. Therefore, this new therapeutic option should be available to all patients with symptomatic systolic heart failure.
An approach to 7-aza-1-phosphanorbornane complexes: strain promoted rearrangement of 1-iminylphosphirane complexes and cycloaddition with olefins (2019)

1-Iminylphosphirane W(CO)5 complexes react with alkenes under an atmosphere of CO at 130 °C to form the original 7-aza-1-phosphanorbornane complexes. The reaction works well with both electron-rich and electron-poor alkenes. On the basis of DFT calculations, we propose a mechanism including the rearrangement of phosphirane into a dipolar five-membered ring and the following cycloaddition of this dipolar intermediate with alkenes.
Approaching ultimate intrinsic signal‐to‐noise ratio with loop and dipole antennas (2017)

Electric dipoles can be advantageous at ultrahigh fields because they can produce both curl-free and divergence-free currents, whereas loops are limited to divergence-free contributions only. Combining loops and dipoles may be optimal for body imaging at 3 T, whereas arrays of loops or dipoles alone may perform better at lower or higher field strengths, respectively. Magn Reson Med 79:1789-1803, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Explanation for the universal low-temperature and dynamical properties of a particular glass (1985)

We present new measurements of the time-dependent specific heat of cubic (KBr${)}_{0.5}$(KCN${)}_{0.5}$. Using a microscopic model of the tunneling centers (180\ifmmode^\circ\else\textdegree\fi{} ${\mathrm{CN}}^{\mathrm{\ensuremath{-}}}$ reorientations) we provide a unified explanation of this specific heat and the low-frequency dielectric loss. Thus, in a crystal exhibiting the universal low-temperature thermal properties and the broad low-frequency dielectric relaxations characteristic of glasses, we have explained both using a microscopic tunneling model.
What are the limitations for the use of Carbopack X as passive or active sampling adsorbent for determination of 1,3-butadiene in ambient environment? (2022)

International audience
Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART): a phase 2b, multiarm, double-blind, randomised placebo-controlled trial (2020)

Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership, UK Multiple Sclerosis Society, and US National Multiple Sclerosis Society.
A PGC‐1alpha:O‐GlcNAc Transferase Complex Regulates Foxo1a Activation in Response to Glucose (2007)

Hepatic gluconeogenesis, which is normally suppressed by insulin, is abnormally activated in diabetes. The transcription factor Foxo1a controls expression of the gluconeogenic enzymes, Pepck and Glc‐6‐Phosphatase. Insulin signaling results in the nuclear exclusion of Foxo1a but post‐translational regulation of transactivation within the nucleus also occurs. Dynamic Modification of proteins by O‐GlcNAc serves as a nutrient and stress sensor and is often competitive with phosphorylation. Anti‐O‐GlcNAc antibodies and lectin studies have shown that Foxo1a is O‐GlcNAcylated. Increased flux into the UDP‐GlcNAc (donor for O‐GlcNAcylation) synthesis pathway increases Foxo1a transcriptional activity in an O‐GlcNAc transferase (OGT) dependent manner. Hyperglycemia increases O‐GlcNAcylation of FOXO1A in heptaoma cells and this increase is reversed by insulin. STZ diabetic rats also show elevated Foxo1a O‐GlcNAcylation and corresponding Pepck and Glc‐6‐Phosphatase mRNA expression. Additionally, we found that OGT interacts with Pgc‐1?, and Pgc‐1? appears to target OGT to Foxo1a, dramatically increasing its O‐GlcNAcylation. We conclude that hyperglycemia increases the O‐GlcNAc modification of Foxo1a resulting in paradoxically elevated hepatic gluconeogenesis, further exacerbating glucose toxicity in diabetes. Supp. by NIH DK61671 and HD13563. GWH receives royalties on sales of CTD110.6. Managed by JHU conflict of interest policies.
CELF RNA binding proteins promote axon regeneration in C. elegans and mammals through alternative splicing of Syntaxins (2016)

Axon injury triggers dramatic changes in gene expression. While transcriptional regulation of injury-induced gene expression is widely studied, less is known about the roles of RNA binding proteins (RBPs) in post-transcriptional regulation during axon regeneration. In C. elegans the CELF (CUGBP and Etr-3 Like Factor) family RBP UNC-75 is required for axon regeneration. Using crosslinking immunoprecipitation coupled with deep sequencing (CLIP-seq) we identify a set of genes involved in synaptic transmission as mRNA targets of UNC-75. In particular, we show that UNC-75 regulates alternative splicing of two mRNA isoforms of the SNARE Syntaxin/unc-64. In C. elegans mutants lacking unc-75 or its targets, regenerating axons form growth cones, yet are deficient in extension. Extending these findings to mammalian axon regeneration, we show that mouse Celf2 expression is upregulated after peripheral nerve injury and that Celf2 mutant mice are defective in axon regeneration. Further, mRNAs for several Syntaxins show CELF2 dependent regulation. Our data delineate a post-transcriptional regulatory pathway with a conserved role in regenerative axon extension.
Insect-Active Toxins with Promiscuous Pharmacology from the African Theraphosid Spider Monocentropus balfouri (2017)

Many chemical insecticides are becoming less efficacious due to rising resistance in pest species, which has created much interest in the development of new, eco-friendly bioinsecticides. Since insects are the primary prey of most spiders, their venoms are a rich source of insect-active peptides that can be used as leads for new bioinsecticides or as tools to study molecular receptors that are insecticidal targets. In the present study, we isolated two insecticidal peptides, µ/ω-TRTX-Mb1a and -Mb1b, from venom of the African tarantula <i>Monocentropus balfouri.</i> Recombinant µ/ω-TRTX-Mb1a and -Mb1b paralyzed both <i>Lucilia cuprina</i> (Australian sheep blowfly) and <i>Musca domestica</i> (housefly), but neither peptide affected larvae of <i>Helicoverpa armigera</i> (cotton bollworms). Both peptides inhibited currents mediated by voltage-gated sodium (Na<sub>V</sub>) and calcium channels in <i>Periplaneta americana</i> (American cockroach) dorsal unpaired median neurons, and they also inhibited the cloned <i>Blattella germanica</i> (German cockroach) Na<sub>V</sub> channel (BgNa<sub>V</sub>1). An additional effect seen only with Mb1a on BgNa<sub>V</sub>1 was a delay in fast inactivation. Comparison of the Na<sub>V</sub> channel sequences of the tested insect species revealed that variations in the S1-S2 loops in the voltage sensor domains might underlie the differences in activity between different phyla.
Enhanced Naive Bayes Classifier for real-time sentiment analysis with SparkR (2016)

Correct and fast sentiment analysis of continuously generated data such as Twitter message is very important for providing real-time customized service to the users. While Naive Bayes Classifier(NBC) is the most popular classifier employed for sentiment analysis, the existing studies on it have been based on single server environment. Consequently, they are not adequate for handling real-time stream data. In this paper, thus, we propose a scheme adopting the Laplace Smoothing technique with Binarized NBC for enhancing the accuracy, and employing SparkR for speed-up via distributed and parallel processing. Computer simulation with Sentiment140 reveals that the proposed approach consistently allows higher accuracy than the existing schemes. It also identifies that the SparkR environment allows faster training than R.
Effects of Lumbar Disk Herniation on the Careers of Professional Baseball Players (2012)

Outcomes after lumbar disk herniation in baseball athletes are currently unknown. It has been postulated that the repetitive torque-producing motions of a baseball player may have negative implications after a disk injury. Sixty-nine lumbar disk herniations (40 treated operatively, 29 nonoperatively) in 64 professional baseball players were identified, and important outcome measures including successful return to play, time to recovery, career longevity, and performance based on vital statistics to each position were documented. Ninety-seven percent of baseball athletes successfully returned to play at an average of 6.6 months after diagnosis. Athletes treated operatively required significantly more time to return to play than those managed nonoperatively (8.7 vs 3.6 months, respectively; P<.0001).
3D printing of wearable fractal-based sensor systems for neurocardiology and healthcare (2017)

Neurocardiology is the pathophysiological interplay of nervous and cardiovascular systems. The communication between the heart and brain has revealed various methodologies in healthcare that could be investigated to study the heart-brain interactions and other cardiovascular and neurological diseases. A textile based wearable nanosensor system in the form of e-bra, e-shirt, e-headband, e-brief, underwear etc, was presented in this SPIE conferences earlier for noninvasive recording of EEG and EKG, and showing the correlation between the brain and heart signals. In this paper, the technology is expanded further using fractal based geometries using 3D printing system for low cost and flexible wearable sensor system for healthcare.
CHOLINE ACETYLTRANSFERASE CONTENT IN DISCRETE REGIONS OF THE RAT BRAIN STEM (1975)

—Choline acetyltransferase (ChAc) content of 50 separate rat brain stem nuclei and cerebellum removed by microdissection was determined using a sensitive radiometric assay. The distribution of ChAc activity is uneven, with extremely high levels in the cranial motor nuclei and the nucleus salivatorius. Low ChAc concentrations were observed in the cranial sensory nuclei, the nuclei of the reticular formation, the raphe nuclei and the nuclei of the acoustic system. The lowest ChAc levels were measured in the cerebellum. Comparison of the distribution of ChAc with histochemical localization of acetylcholinesterase revealed generally good agreement, and notable exceptions are discussed.
Ten things the hematologist wants you to know about CAR-T cells (2020)

Chimeric antigen-receptor T cells, CAR-T cells, are genetically engineered T-cells, and after decades of development, CAR-T constructs are approved for selected relapsed and refractory (r/r) CD19-positive hematological malignancies and are currently being tested in cancer, infectious disease and autoimmunity About onethird of CAR-T patients require ICU treatment Here are ten things your hematologist wants you to know about CAR-T cells.
SYST-28 FUNCTIONAL MAPPING REVEALS WIDESPREAD REMODELLING AND A NOVEL TARGETABLE PTP4A2-ROBO1 SIGNALING AXIS AT GLIOBLASTOMA RECURRENCE (2023)

Abstract Resistance to genotoxic therapies and tumor recurrence are hallmarks of glioblastoma (GBM), an aggressive brain tumor. Here, we explore the functional drivers of post-treatment recurrent GBM. By conducting genome-wide CRISPR-Cas9 screens in patient-derived GBM models, we uncover distinct genetic dependencies in recurrent tumor cells that were absent in their patient-matched primary predecessors, accompanied by increased mutational burden and differential transcript and protein expression. These analyses map a multilayered genetic response to drive tumor recurrence, identifying protein tyrosine phosphatase 4A2 (PTP4A2) as a novel modulator of self-renewal, proliferation and tumorigenicity at GBM recurrence. Mechanistically, genetic perturbation or small molecule inhibition of PTP4A2 represses axon guidance activity through a dephosphorylation axis with roundabout guidance receptor 1 (ROBO1), exploiting a functional dependency on ROBO signaling. Roundabout guidance receptor 1 (ROBO1) protein is involved in axonal guidance during neurodevelopment and aberrant ROBO1 signaling axis is associated with higher tumorigenicity in GBM. ROBO1 was highly expressed on the surface of malignant and treatment-refractory brain tumor initiating cells (BTICs) in rGBM, brain metastasis (BM) and medulloblastoma (MB). Importantly, engineered anti-ROBO1 single-domain antibodies also mimic the effects of PTP4A2 inhibition. We therefore developed and validated second-generation CAR-T cells against ROBO1, which demonstrated upregulation of activation markers, enhanced cytokine release, markedly increased proliferation, and induction of potent and specific tumor cell death compared to untransduced cells in all the three brain cancers. These findings were further validated in vivo in rGBM, MB and BM models, where ROBO1 CAR-T cells showed significant reduction in tumor burden and increase in survival of treated mice. We conclude that functional reprogramming drives tumorigenicity and dependence on a multi-targetable PTP4A2-ROBO1 signaling axis at GBM recurrence.
Electric-Line Milling System Removes Stuck Frac Sleeve without Damaging the Subsurface Safety Valve Landing Nipple (2013)

Abstract This is a case study for a well intervention job that was conducted in the Prudhoe Bay Unit field, Alaska. It describes the successful use of an electric line milling system to remove a protective frac sleeve that was stuck in a subsurface safety valve (SSSV) landing nipple. Past attempts to remove the sleeve with conventional methods were unsuccessful. Those attempts included slickline, coiled tubing (CT), and pulling 110,000 lbf with a workover rig using a through-tubing work string. At the time, the sleeve did not interfere with production, so it was left in the well. However, an unrelated tubing leak developed below the stuck frac sleeve. The well had to be shut in until the frac sleeve could be pulled to allow installation of a tubing patch. Milling the frac sleeve with coiled tubing or replacing the entire tubing string with a workover rig was considered. However, cost and time could be reduced if the frac sleeve could be milled with an electric-line (e-line) conveyed bottomhole assembly (BHA). The e-line tool string included a wireline release device, an electric-over-hydraulic tractor with stroking tool, electric milling motor, and burning shoe with integral centralizer and no-go. The burning shoe was designed to reduce the outside diameter (OD) of the frac sleeve but preserve the packing bore inside diameter (ID) of the SSSV landing nipple. The tractor-stroker-miller tool string was run in the well and tagged the sleeve at 2,119 ft measured depth (MD) where milling continued for approximately 4 ½ hours. After E-line milling was completed, slickline was rigged up for fishing operations and successfully pulled the frac sleeve. The tubing repair was completed and the well was returned to production. This intervention technology can be used in other wellbores requiring precision milling. The solution proved successful and is a cost-effective alternative to conventional methods for milling obstructions.
Robust control for a class of interval model: Application to the force control of piezoelectric cantilevers (2010)

A method to design robust performances controllers is proposed in this paper. The method is valuable for a class of uncertain parametric systems: systems with zero-order numerator. In this work, interval model that accounts parametric uncertainties is described using interval analysis. Robust controller is derived by combining the interval arithmetic with the classical direct synthesis. As the derived controller is also an interval, we prove using numerical analysis that the midpoint can be taken as the final controller to be implemented. The proposed design method is applied to the control of manipulation force in piezocantilevers where the compliance of the manipulated objects is uncertain. The experimental results show the efficiency of the proposed method.
New Models of Deep Comprehension (2014)

This chapter presents new models of comprehension that we have been develop­
ing in recent years. These models focus on deeper levels of comprehension (which 
involve pragmatics, inferences, and world knowledge) rather than shallow levels 
of comprehension (such as lexical processing, syntactic parsing, and the interpre­
tation of explicit text). Early research in the psychology of language and discourse 
processing emphasized the shallow levels of comprehension. It was easier to 
measure and manipulate factors directly associated with the surface text than to 
struggle with barely visible mechanisms at the deep levels. There were many 
theories about the surface levels, enough theories to occupy everyone’s time for 
several decades. However, researchers came to recognize the pressing need to 
explore the deep levels. They discovered that the deep levels often have a greater 
impact on reading time, memory, decision making, and judgment than do the 
shallow levels. They also identified interesting ways in which deep levels inter­
acted with shallow levels of processing. The Zeitgeist has shifted from the shallow 
to the deep levels of comprehension.
Recent Advancements in IoT Implementation for Environmental, Safety, and Production Monitoring in Underground Mines (2023)

Internet of Things (IoT) technology has been widely used for real-time monitoring of the environment, safety and production in underground mines. This paper presents the basic structure of a Mine Internet of Things (MIoT) system based on a widely used three-layer IoT architecture, classifies types of sensors commonly used in underground mines by specific application, and introduces available wired and wireless communication technologies and network topologies that can be applied in underground mines. This paper provides a comprehensive review of recent developments in IoT applications in underground mines to monitor various environmental parameters, including mine gas and dust concentrations, temperature, humidity and airflow, groundwater, ground support and seismic activity. MIoT applications for fire and hazard detection, personnel and equipment positioning, and production safety management have also been investigated. This paper highlights key challenges for the broad application of IoT technology in underground mines such as operation disruption, additional investment, limited battery life, poor quality of underground communication, and difficulty in data management. Further research on novel advanced techniques, such as self-powered sensors, MIoT standardization and underground wireless communication technologies, is essential to improve the applicability and effectiveness of IoT applications in underground mines.
Dynamics of a deflated vesicle in bipolar pulsed electric field (2020)

submitted to Soft Matter
Supplementary Figure from Dominant Role of Oncogene Dosage and Absence of Tumor Suppressor Activity in &lt;i&gt;Nras-&lt;/i&gt;Driven Hematopoietic Transformation (2023)

&lt;p&gt;Supplementary Figure 2 - PDF file 177K, Data showing survival and Hematologic Parameters of Nras heterozygous, hemizygous and homozygous mice&lt;/p&gt;
Reductive decomplexation of π-allyltricarbonyliron lactone complexes using sodium naphthalenide as a route to stereodefined 1,7-diols and 2,3-diene-1,7-diols (2003)

Treatment of pi-allyltricarbonyliron lactone complexes, that contain an adjacent leaving group, with lithium naphthalenide causes decomplexation to acyclic dienols in excellent yield and without any stereochemical scrambling of the allylic centre. When an endo complex is employed (E,E)-geometry prevails with good selectivity whereas (Z,E)-geometry dominates in the case of exo complexes. A mechanism consistent with the observed stereo- and regiochemistry is proposed.
CLSM as Quantitative Method to Determine the Size of Drug Crystals in a Solid Dispersion (2011)

CLSM is a useful technique to determine the particle size in a powder mixture. Furthermore, CLSM can be used to determine the drug crystal size over a broad size distribution. A limitation of the method is that the drug should be autofluorescent.
Rate-Transient Analysis for Multistage Fractured Horizontal Wells in Conventional and Un-Conventional Homogeneous and Naturally Fractured Reservoirs (2016)

Abstract We investigate the rate-transient behavior of multistage fractured horizontal wells in conventional and unconventional homogeneous and naturally fractured reservoirs, the latter of which can contain any spatial distribution of finite- or infinite-conductivity fractures of arbitrary length and orientation. The number and type of fractures (hydraulic or natural) intersecting the wellbore and self-intersecting is unlimited. We show that there are many factors that dominate the ratetransient behavior of horizontal wells intersected by multiple hydraulic fractures in naturally fractured reservoirs, such as fracture conductivity, length, and distribution, as well as whether or not fractures intersect the wellbore. It is shown that the magnitude of the fracture conductivity is one of the most important parameters that affects the production performance of multistage fractured horizontal wells. It is also shown that, as the space increases between hydraulic and natural fractures intersecting a horizontal well, the fracture pseudosteady-state flow regime tends to disappear. Using the pressure and flow rate equivalency principle, we show that a production rate and/or cumulative production data set can be transformed into an equivalent pressure or pressure derivative data set. This is also very important for unconventional gas and oil reservoirs, where the boundary-dominated pseudosteady-state flow regime takes years to develop. A new technique is presented for determining stimulated reservoir volume (SRV) and production forecasting. It is shown that rate derivatives exhibit unusual behavior, from which system identification and flow regime analysis become impossible. The material balance time does not totally correct the unusual behavior of the rate derivative. However, the deconvolved pressure of the cumulative production derivatives behave like pressure derivatives.
Understanding Microplasmas (2011)

Microplasmas are operated around atmospheric pressure exhibiting pronounced non-equilibrium characteristics, i.e. they possess energetic electrons while ions and neutrals remain cold. They have gained significant interest due to their enormous application potential e.g. in the biomedical, surface modification and light source areas, just to name a few. Many different configurations are in use. Their understanding and quantification is mandatory for further progress in applications. We report on recent progress in the diagnostics and simulation of the entire microplasma system from gas introduction, via the plasma discharge up to the samples at the example of a plasma jet operated in He/O2 in an ambient air environment.
Reconsidering the causality of TIA1 mutations in ALS (2017)

International audience