gebhart/patrepeval huggingface dataset:
Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in the USA (2018)

Nintedanib has been approved for the treatment of idiopathic pulmonary fibrosis (IPF) in more than 60 countries, including the USA [1]. In the two phase III INPULSIS trials, nintedanib reduced disease progression by reducing decline in forced vital capacity [2]. Most patients were able to manage the side-effects of nintedanib, with 19.3% of patients treated with nintedanib versus 13.0% treated with placebo permanently discontinuing the study medication due to adverse events. The most frequent adverse events were gastrointestinal, particularly diarrhoea. The proportion of patients who had one or more serious adverse events was similar between nintedanib and placebo (30.4% versus 30.0%). The safety and tolerability profile of nintedanib in patients with IPF in the clinical setting is consistent with the product label <http://ow.ly/Nulb30jPAld> The authors would like to acknowledge the contribution of Alexandar Allinger, Boehringer Ingelheim Pharma GmbH & Co. KG (Ingelheim am Rhein, Germany) to the acquisition and analysis of the data. Medical writing assistance was provided by Julie Fleming and Wendy Morris of FleishmanHillard Fishburn (London, UK), which was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc. All authors were involved in the interpretation of the data and writing of this letter and have approved the final version.
Skeletal muscle afferent sensitivity in Interstitial Lung Disease-interim analysis of a randomized cross-over study (2021)

<b>Background:</b> Physiological mechanisms of exercise intolerance in fibrotic Interstitial Lung Disease (ILD) are poorly understood. In other chronic diseases (e.g., COPD), there is emerging evidence that the sensitivity of metabolically responsive skeletal muscle afferents (muscle metaboreflex) is augmented. This can contribute to exercise intolerance through dyspnoea, exaggerated sympathetic vasoconstriction and hypoperfusion of the active muscle. <b>Aims and Objectives:</b> We hypothesize that muscle metaboreflex sensitivity is augmented in fibrotic ILD. <b>Methods:</b> Five fibrotic ILD patients (2 female, 72±6.8yrs, TLC 61±9.6% pred., DLCO 44±15% pred., FEV1/FVC&gt;0.7, fibrosis on HRCT) and seven healthy controls (3 female, 66±6.4yrs) were recruited. In a randomized cross-over design, participants completed two min of rhythmic handgrip followed by either i) two min of post-exercise circulatory occlusion (PECO trial) to isolate muscle metaboreflex activation or ii) rested for four min (control trial). Minute ventilation (V̇<sub>E</sub>), mean arterial pressure (MAP) and heart rate (HR) were measured and analysed using a mixed model ANOVA. Comparison of intra-individual differences between PECO and the corresponding control period (i.e. muscle metaboreflex sensitivity) was assessed using an unpaired t-test. <b>Results:</b> Exercise increased V̇<sub>E</sub>, MAP and HR (p&lt;0.05) with no difference between groups. V̇<sub>E</sub> and MAP remained elevated during PECO (p&lt;0.05). Within individuals, PECO increased V̇<sub>E</sub> more in the healthy than ILD group (p=0.026), while MAP responses were not different (p=0.40). <b>Conclusions:</b> These interim findings suggest that in contrast to COPD, muscle metaboreflex sensitivity is not augmented in ILD.
High Energy Density Poly(acrylonitrile)-Sulfur Composite-Based Lithium-Sulfur Batteries (2013)

Sulfur-poly(acrylonitrile) (SPAN) composites were synthesized from different poly(acrylonitrile)- (PAN) sulfur mixtures. This way it was possible to increase the sulfur content and concomitantly the measured specific capacity of the final lithium-sulfur batteries from 300 mAh/gcathode to 440 mAh/gcathode (629 mAh/gcomposite, 1429 mAh/gsulfur). A maximum of 44 wt-% of covalently bound sulfur was reached using a PAN-sulfur ratio of 1:15 (wt/wt). Virtually no loss of capacity was observed during the first 40 cycles.
Triggered single-photon generation and resonance fluorescence in ultra-low loss integrated photonic circuits (2022)

A central requirement for photonic quantum information processing systems lies in the combination of nonclassical light sources and low-loss, phase-stable optical modes. While substantial progress has been made separately towards ultra-low loss, $\leq1$ dB/m, chip-scale photonic circuits and high brightness single-photon sources, integration of these technologies has remained elusive. Here, we report a significant advance towards this goal, in the hybrid integration of a quantum emitter single-photon source with a wafer-scale, ultra-low loss silicon nitride photonic integrated circuit. We demonstrate triggered and pure single-photon emission directly into a Si$_3$N$_4$ photonic circuit with $\approx1$ dB/m propagation loss at a wavelength of $\approx920$ nm. These losses are more than two orders of magnitude lower than reported to date for any photonic circuit with on-chip quantum emitter sources, and $&gt;50$ % lower than for any prior foundry-compatible integrated quantum photonic circuit, to the best of our knowledge. Using these circuits we report the observation of resonance fluorescence in the strong drive regime, a milestone towards integrated coherent control of quantum emitters. These results constitute an important step forward towards the creation of scaled chip-integrated photonic quantum information systems.
Anomeric specificity of D-xylose isomerase (1992)

Crystal structures of complexes of D-xylose isomerase with deoxysugars have been determined. Deoxynojirimycin is a structural analogue of alpha-pyranose and mimics the binding of these aldose substrates. The structure of this complex supports the hypothesis that an imidazole group catalyzes ring opening of the pyranose. The steric restrictions in the active site of the enzyme prevent a beta-pyranose from binding in the same way. For the reverse reaction with ketoses, the anomeric specificity is less certain. Dideoxyimino-D-glucitol is a structural analogue of the ketose alpha-D-furanose. The binding of the inhibitor dideoxyimino-D-glucitol to the crystals of the enzyme does not mimic the binding of the reactive alpha-D-fructofuranose. Superposition of the nonphysiological substrate alpha-D-fructofuranose onto the atomic positions of dideoxyimino-D-glucitol is not possible due to the steric restrictions of the active site. However, by utilizing the approximate 2-fold symmetry of the sugar, a stereochemically sensible model is produced which is consistent with other data. In addition to reaction with alpha-D-furanose, the enzyme probably reacts with open ring keto sugars which are present at significant concentrations. Other sugars which resemble furanoses either do not inhibit significantly or are not observed in the crystals bound in a single conformation.
Towards cube-sized compute nodes: Advanced packaging concepts enabling extreme 3D integration (2017)

Novel heat removal and power delivery topologies are required to enable `extreme 3D integration' with cube-sized compute nodes. Therefore, a technology roadmap is presented supporting memory-on-logic and logic-on-logic in the medium and long-term, by (i) dual-side cooling and integrated voltage regulators, and (ii) interlayer cooling and electrochemical power delivery.
Constraint-based scheduling (2001)

Constraint-based scheduling has become the dominant form of modeling and solving scheduling problems. Recently, due to ever more powerful embedded processors, it has become possible to embed and run constraint-based schedulers on-line even for fast processes such as product assembly sequencing. This makes constraint-based scheduling interesting to the control community as a new tool for system control, distributed and reconfigurable control, and the integration of various planning, scheduling, and control tasks. This tutorial gives a brief introduction to constraint-based scheduling, generic constraint programming techniques for modeling and solving scheduling problems, and a concrete real-time application example.
Resurgence of Hypothermia as a Treatment for Brain Injury (2004)

Like all homeothermic animals, humans maintain their thermal core temperature within a narrow range despite variations in environmental conditions and endogenous heat production. Thermoregulation is under central nervous system (CNS) control, mainly in the hypothalamus, and body functions are impaired if brain temperature deviates from the normothermic range. With prolonged exposure to an extreme cold challenge in which the thermoregulatory system is overwhelmed, core body temperature falls below the desired temperature range (i.e., hypothermia) and, unless reversed, can lead to death (1). On the other hand, temperature can be modulated in a therapeutic manner to achieve organ protection. Hypothermia-induced protection of tissue has interested scientists and clinicians since the 19th century, when hypothermia was first utilized in the clinical setting as a local anesthetic during surgical procedures.
Interaction of Pyrrolobenzodiazepine (PBD) Ligands with Parallel Intermolecular G-Quadruplex Complex Using Spectroscopy and ESI-MS (2012)

Studies on ligand interaction with quadruplex DNA, and their role in stabilizing the complex at concentration prevailing under physiological condition, has attained high interest. Electrospray ionization mass spectrometry (ESI-MS) and spectroscopic studies in solution were used to evaluate the interaction of PBD and TMPyP4 ligands, stoichiometry and selectivity to G-quadruplex DNA. Two synthetic ligands from PBD family, namely pyrene-linked pyrrolo[2,1-c][1,4]benzodiazepine hybrid (PBD1), mixed imine-amide pyrrolobenzodiazepine dimer (PBD2) and 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4) were studied. G-rich single-stranded oligonucleotide d(5'GGGGTTGGGG3') designated as d(T(2)G(8)), from the telomeric region of Tetrahymena Glaucoma, was considered for the interaction with ligands. ESI-MS and spectroscopic methods viz., circular dichroism (CD), UV-Visible, and fluorescence were employed to investigate the G-quadruplex structures formed by d(T(2)G(8)) sequence and its interaction with PBD and TMPyP4 ligands. From ESI-MS spectra, it is evident that the majority of quadruplexes exist as d(T(2)G(8))(2) and d(T(2)G(8))(4) forms possessing two to ten cations in the centre, thereby stabilizing the complex. CD band of PBD1 and PBD2 showed hypo and hyperchromicity, on interaction with quadruplex DNA, indicating unfolding and stabilization of quadruplex DNA complex, respectively. UV-Visible and fluorescence experiments suggest that PBD1 bind externally where as PBD2 intercalate moderately and bind externally to G-quadruplex DNA. Further, melting experiments using SYBR Green indicate that PBD1 unfolds and PBD2 stabilizes the G-quadruplex complex. ITC experiments using d(T(2)G(8)) quadruplex with PBD ligands reveal that PBD1 and PBD2 prefer external/loop binding and external/intercalative binding to quadruplex DNA, respectively. From experimental results it is clear that the interaction of PBD2 and TMPyP4 impart higher stability to the quadruplex complex.
Hydrophobic and Hofmeister Effects on the Adhesion of Spider Silk Proteins onto Solid Substrates:  An AFM-Based Single-Molecule Study (2007)

AFM-based single-molecule force spectroscopy has been used to study the effect of Hofmeister salts and protein hydrophobicity on the adhesion of recombinant spider silk proteins onto solid substrates. Therefore, a molecular probe consisting of a spider silk protein and an AFM tip has been developed, which (i) is a well-defined, small system that can be simulated by molecular dynamics simulations, (ii) allows access to the whole soluble concentration range for ions, and (iii) provides the distribution of desorption forces rather than just ensemble-averaged mean values. The measured desorption forces follow the Hofmeister series for anions (H2PO4-, Cl-, I-) with a stabilizing energy of more than 15 kBT for 5 M NaH2PO4. Moreover, this effect is influenced by the hydrophobicity of the spider silk protein, indicating that hydrophobic and Hofmeister effects are closely related.
Advancements in H Class Gas Turbines and Combined Cycle Power Plants (2018)

The power generation industry is facing unprecedented challenges. High fuel costs combined with an increased penetration of renewable power has resulted in greater demand for high efficiency and operational flexibility. Imperative for a reduced carbon footprint places an even higher premium on efficiency. Power producers are seeking highly efficient, reliable, and operationally flexible solutions that provide long-term profitability in a volatile environment. New generation must also be cost-effective to ensure affordability for both domestic and industrial consumers. Gas turbine combined cycle power plants provide reliable, dispatch-able generation with low cost of electricity, reduced environmental impact, and improved flexibility. GE’s air-cooled, H-class gas turbines (7/9HA) are engineered to achieve greater than 63% net, combined cycle efficiency while delivering operational flexibility through deep, emission-compliant turndown and high ramp rates. The largest of these gas turbines, the 9HA.02, exceeds 64% combined cycle efficiency (net, ISO) in a 1 × 1, single-shaft configuration. In parallel, the power plant has been configured for rapid construction and commissioning enabling timely revenue generation for power plant developers and owners. The HA platform is enabled by 1) use of a simple air-cooling system for the turbine section that does not require external heat exchange and the associated cost and complexity, and 2) use of well-known materials and coatings with substantial operating experience at high firing temperatures. Key technology improvements for the HA’s include advanced cooling and sealing, utilization of unsteady aerodynamic methodologies, axially staged combustion and next generation thermal barrier coating (TBC). Validation of the architecture and technology insertion is performed in a dedicated test facility over the full operating range. As of February 2018, a total of 18 HA power plants have achieved COD (Commercial Operation). This paper will address three topics relating to the HA platform: 1) gas turbine product technology, 2) gas turbine validation and 3) integrated power plant commissioning and operating experience.
Single Image Deraining Network with Rain Embedding Consistency and Layered LSTM (2022)

Single image deraining is typically addressed as residual learning to predict the rain layer from an input rainy image. For this purpose, an encoder-decoder network draws wide attention, where the encoder is required to encode a high-quality rain embedding which determines the performance of the subsequent decoding stage to reconstruct the rain layer. However, most of existing studies ignore the significance of rain embedding quality, thus leading to limited performance with over/under-deraining. In this paper, with our observation of the high rain layer reconstruction performance by an rain-to-rain autoencoder, we introduce the idea of "Rain Embedding Consistency" by regarding the encoded embedding by the autoencoder as an ideal rain embedding and aim at enhancing the deraining performance by improving the consistency between the ideal rain embedding and the rain embedding derived by the encoder of the deraining network. To achieve this, a Rain Embedding Loss is applied to directly supervise the encoding process, with a Rectified Local Contrast Normalization (RLCN) as the guide that effectively extracts the candidate rain pixels. We also propose Layered LSTM for recurrent deraining and fine-grained encoder feature refinement considering different scales. Qualitative and quantitative experiments demonstrate that our proposed method outperforms previous state-of-the-art methods particularly on a real-world dataset. Our source code is available at http://www.ok.sc.e.titech.ac.jp/res/SIR/.
Effects of gamma-Butyrobetaine and Mildronate on Nitric Oxide Production in Lipopolysaccharide-Treated Rats (2004)

Production of nitric oxide was measured in lipopolysaccharide-treated rats (10 mg/kg, 4 hr) using the electron paramagnetic resonance method. As compared to the control animals, the nitric oxide level in liver of lipopolysaccharide-treated rats increased from 27.6+/-4.7 to 1485+/-129 ng/g tissue, in heart from 4.8+/-0.7 to 271+/-26 ng/g tissue, in blood from 33.6+/-12.4 to 638+/-136 ng/g tissue, in kidney from 3.3+/-0.5 to 356+/-31 ng/g tissue, in brain cortex from 46.0+/-3.4 to 227+/-27 ng/g tissue, in cerebellum from 27.7+/-2.6 to 218+/-30 ng/g tissue, and in testes from 13.8+/-1.1 to 86+/-8 ng/g tissue. Administration of the antiischaemic drug, mildronate (120 mg/kg) caused a significant twofold decrease of the nitric oxide level in brain cortex and cerebellum 1 hr after drug administration. Its natural analogue gamma-butyrobetaine (30 mg/kg) triggered a twofold decrease of the nitric oxide concentration in all studied tissues 30 min. after the administration. Nitric oxide reached the initial level 2 hr later. Neither mildronate nor gamma-butyrobetaine could inhibit the inducible nitric oxide synthase in vitro. Analogues of gamma-butyrobetaine appear to be prospective drugs for the treatment of circulatory complications of sepsis.
2-Halogeno-3-morpholinothietan 1,1-dioxides. Kinetics of base catalysed cis–trans-isomerization and hydrogen–deuterium exchange (1974)

The kinetics of base catalysed H–D exchange at position 2 and cis–trans-isomerization have been measured in CD3CN–D2O for a series of 2-halogeno-3-morpholinothietan 1,1-dioxides (1)–(6). The isomerization and exchange rates depend upon the nature of the halogen and are in the order I > Br > CI. The results are rationalized in terms of electrostatic and/or steric effects. The values of the ratio Kex/Kis are ca. 1 for compounds (1)–(3) and further support the known configurational instability of strained α-sulphonyl carbanions.
Data-Driven Subsynchronous Oscillation Identification Using Field Synchrophasor Measurements (2021)

With the increasing development of renewable energy and high-voltage direct current (HVDC) transmission technology, the integration of power electronics-interfaced components has caused sub-&#x002F;super-synchronous inter-harmonics into power signals, yielding the subsynchronous oscillations (SSOs). Online monitoring and identification of SSOs are crucial to the secure and stable operation of power systems. This paper proposes a data driven SSOs identification method using realistic phasor measurement unit (PMU) data. Three features are extracted via the analysis of a large number of historical PMU data, which can reflect the SSO features and the interference level. An SSOs identification method is proposed through a multiple-support vector machine (SVM) model. It allows us to adaptively select the proper classifier among the multiple-SVM models according to the interference level estimated by the extracted features. This significantly improves the identification accuracy under both low and high interference inputs of a practical power grid. An automatic update function based on incremental learning is also developed to enhance the model performance when the SSO data are subject to new features. Experimental results using field-measured PMU data validate the advantages of the proposed method over other alternatives.
Detection of Microsatellite Instability and Loss of Heterozygosity Using DNA Extracted from Formalin-Fixed Paraffin-Embedded Tumor Material by Fluorescence-Based Multiplex Microsatellite PCR (2003)

Microsatellites are widely distributed highly repetitive DNA sequences composed of di-, tri-, or tetranucleotide repeats (1). They are spread over the whole human genome and are located between and within genes. Physiologically, they exhibit high levels of polymorphism, relative to different chromosomal loci, and within different individuals, different microsatellite lengths can even be noted between two alleles of the same gene (1). Although the role of microsatellites in the genome and their evolutionary mechanisms are still incompletely understood, they are widely used tools in genetic mapping studies and as markers for prediction of disease (2,3).
In Vivo Biocompatibility of Single Walled Carbon Nanotubes (2020)

Ovarian cancer patient prognosis and quality of life are significantly affected by the failure to accurately diagnose disease at early stage. Currently, less than 15% of ovarian cancer patients are diagnosed at stage 1, when 5-year survival rates are near 93%. Early detection may save more than 80% of women diagnosed with ovarian cancer. Our goal is to develop clinical long-term implantable carbon nanotube-based sensors for ovarian cancer biomarkers to transiently detect and monitor their levels in patients. The proposed sensors will harness the unique optical properties and sensitivity of single-walled carbon nanotubes. To improve sensitivity and specificity of such sensors, previously developed to detect ovarian cancer biomarkers in vivo, we used molecular perceptron—data analytics-based methods to detect specific spectroscopic fingerprints from the binding of protein biomarkers to the nanotube surface.
Magnetic modulation doping in topological insulators toward higher-temperature quantum anomalous Hall effect (2015)

Quantum anomalous Hall effect (QAHE), which generates dissipation-less edge current without external magnetic field, is observed in magnetic-ion doped topological insulators (TIs) such as Cr- and V-doped (Bi,Sb)2Te3. The QAHE emerges when the Fermi level is inside the magnetically induced gap around the original Dirac point of the TI surface state. Although the size of gap is reported to be about 50 meV, the observable temperature of QAHE has been limited below 300 mK. We attempt magnetic-Cr modulation doping into topological insulator (Bi,Sb)2Te3 films to increase the observable temperature of QAHE. By introducing the rich-Cr-doped thin (1 nm) layers at the vicinity of both the surfaces based on non-Cr-doped (Bi,Sb)2Te3 films, we have succeeded in observing the QAHE up to 2 K. The improvement in the observable temperature achieved by this modulation-doping appears to be originating from the suppression of the disorder in the surface state interacting with the rich magnetic moments. Such a superlattice designing of the stabilized QAHE may pave a way to dissipation-less electronics based on the higher-temperature and zero magnetic-field quantum conduction.
Probing the Roles of Active Site Residues in D-Xylose Isomerase (1995)

The roles of active site residues His54, Phe94, Lys183, and His220 in the Streptomyces rubiginosus D-xylose isomerase were probed by site-directed mutagenesis. The kinetic properties and crystal structures of the mutant enzymes were characterized. The pH dependence of diethylpyrocarbonate modification of His54 suggests that His54 does not catalyze ring-opening as a general acid. His54 appears to be involved in anomeric selection and stabilization of the acyclic transition state by hydrogen bonding. Phe94 stabilizes the acyclic-extended transition state directly by hydrophobic interactions and/or indirectly by interactions with Trp137 and Phe26. Lys183 and His220 mutants have little or no activity and the structures of these mutants with D-xylose reveal cyclic alpha-D-xylopyranose. Lys183 functions structurally by maintaining the position of Pro187 and Glu186 and catalytically by interacting with acyclic-extended sugars. His220 provides structure for the M2-metal binding site with properties which are necessary for extension and isomerization of the substrate. A second M2 metal binding site (M2') is observed at a relatively lower occupancy when substrate is added consistent with the hypothesis that the metal moves as the hydride is shifted on the extended substrate.