gebhart/patrepeval huggingface dataset:
The proximal pathway of metabolism of the chlorinated signal molecule differentiation-inducing factor-1 (DIF-1) in the cellular slime mould Dictyostelium (1995)

Stalk cell differentiation during development of the slime mould Dictyostelium is induced by a chlorinated alkyl phenone called differentiation-inducing factor-1 (DIF-1). Inactivation of DIF-1 is likely to be a key element in the DIF-1 signalling system, and we have shown previously that this is accomplished by a dedicated metabolic pathway involving up to 12 unidentified metabolites. We report here the structure of the first four metabolites produced from DIF-1, as deduced by m.s., n.m.r. and chemical synthesis. The structures of these compounds show that the first step in metabolism is a dechlorination of the phenolic ring, producing DIF metabolite 1 (DM1). DM1 is identical with the previously known minor DIF activity, DIF-3. DIF-3 is then metabolized by three successive oxidations of its aliphatic side chain: a hydroxylation at omega-2 to produce DM2, oxidation of the hydroxy group to a ketone group to produce DM3 and a further hydroxylation at omega-1 to produce DM4, a hydroxyketone of DIF-3. We have investigated the enzymology of DIF-1 metabolism. It is already known that the first step, to produce DIF-3, is catalysed by a novel dechlorinase. The enzyme activity responsible for the first side-chain oxidation (DIF-3 hydroxylase) was detected by incubating [3H]DIF-3 with cell-free extracts and resolving the reaction products by t.l.c. DIF-3 hydroxylase has many of the properties of a cytochrome P-450. It is membrane-bound and uses NADPH as co-substrate. It is also inhibited by CO, the classic cytochrome P-450 inhibitor, and by several other cytochrome P-450 inhibitors, as well as by diphenyliodonium chloride, an inhibitor of cytochrome P-450 reductase. DIF-3 hydroxylase is highly specific for DIF-3: other closely related compounds do not compete for the activity at 100-fold molar excess, with the exception of the DIF-3 analogue lacking the chlorine atom. The Km for DIF-3 of 47 nM is consistent with this enzyme being responsible for DIF-3 metabolism in vivo. The two further oxidations necessary to produce DM4 are also performed in vitro by similar enzyme activities. One of the inhibitors of DIF-3 hydroxylase, ancymidol (IC50 67 nM) is likely to be particularly suitable for probing the function of DIF metabolism during development.
Computer‐Aided Design and Synthesis of 1‐{4‐[(3,4‐Dihydroxybenzylidene)amino]phenyl}‐5‐oxopyrrolidine‐3‐carboxylic Acid as an Nrf2 Enhancer (2018)

Abstract Invited for this month's cover is Prof. Arie Gruzman (Bar‐Ilan University) and collaborators who have developed an Nrf2 enhancer. This compound activated the Nrf2 transduction pathway and because of this the translation of dozens of antioxidant cytoprotective proteins in a dose‐ and time‐dependent manner and protected PC‐12 cells against oxidative stress. Considering the imbalance between production and elimination of oxidative species involved in the pathophysiology of many human diseases, this compound is a promising starting point for the development of novel therapeutics for the treatment of oxidative‐stress‐related diseases. Read the full text of the article at 10.1002/cplu.201700539 .
Comparative Analysis of Ankle Arthroplasty Versus Ankle Arthrodesis (1988)

In a retrospective study of 41 patients with total ankle arthroplasty (25 patients) and ankle arthrodesis (18 patients), the mean follow-up period was 3.8 years for total ankle arthroplasties and 3.3 for ankle arthrodeses. Sixteen of the 23 ankle arthroplasty patients, and 17 of the 18 arthrodesis patients had good or excellent results. Total ankle arthroplasty was successful in patients with rheumatoid arthritis, but not posttraumatic arthrosis. Total ankle arthroplasty is indicated in rheumatoid patients with severe ankle involvement who have not responded to medical management. It also may be used in the elderly or debilitated patients who will place minimal stress on the ankle. The elderly may not tolerate the prolonged immobilization or repeated operations that fusion may require. Total ankle arthroplasty should not be used in young patients with posttraumatic arthrosis.
Integrative phenotyping framework (iPF): integrative clustering of multiple omics data identifies novel lung disease subphenotypes (2015)

Identification of subclusters with distinct clinical and biomolecular characteristics suggests that integration of phenomic and other omics information could lead to identification of novel mechanism-based disease sub-phenotypes.
A stochastic wire length distribution for gigascale integration (GSI) (2002)

Based on Rent's Rule, a well established empirical relationship, a rigorous derivation of a complete wire length distribution for on-chip random logic networks is performed. This distribution is used to enhance a critical path model; to derive a preliminary dynamic power dissipation model; and to describe optimal architectures for multilevel wiring networks that provide maximum interconnect density.
Intranasal delivery of erythropoietin plus insulin-like growth factor–I for acute neuroprotection in stroke (2009)

The data demonstrate that intranasal EPO plus IGF-I penetrates into the brain more efficiently than other drug delivery methods and could potentially provide a fast and efficient treatment to prevent chronic effects of stroke.
Performance of burst-mode LTE-A signal on a converged RoF and W-band wireless system (2014)

We propose and experimentally investigate a high-speed burst-mode LTE-A signal transmission on a seamlessly converged RoF and millimeter-wave system at 90 GHz. Satisfactory transmission performance over the converged RoF and a 1.2-m 90-GHz wireless link is achieved. The obtained results confirm the potential to use the system in future high-speed mobile and broadband access networks.
Characterization of Welds (1993)

Abstract This article describes the characterization of welds as a sequence of procedures, where each procedure is concerned with a finer scale of detail. The first level of characterization involves information that may be obtained by direct visual inspection and measurement of the weld. The article discusses nondestructive evaluation of welds by encompassing techniques that are used to characterize the locations and structure of internal and surface defects, including radiography, ultrasonic testing, and liquid penetrant inspection. It reviews the macrostructural characterization of a sectioned weld, including features such as number of passes; weld bead size, shape, and homogeneity; and the orientation of beads in a multipass weld. The article provides examples that describe how welds are characterized according to the procedures.
Strong and Biostable Hyaluronic Acid–Calcium Phosphate Nanocomposite Hydrogel via in Situ Precipitation Process (2016)

Hyaluronic acid (HAc) hydrogel exhibits excellent biocompatibility, but it has limited biomedical application due to its poor biomechanical properties as well as too-fast enzymatic degradation. In this study, we have developed an in situ precipitation process for the fabrication of a HAc-calcium phosphate nanocomposite hydrogel, after the formation of the glycidyl methacrylate-conjugated HAc (GMHA) hydrogels via photo-cross-linking, to improve the mechanical and biological properties under physiological conditions. In particular, our process facilitates the rapid incorporation of calcium phosphate (CaP) nanoparticles of uniform size and with minimal agglomeration into a polymer matrix, homogeneously. Compared with pure HAc, the nanocomposite hydrogels exhibit improved mechanical behavior. Specifically, the shear modulus is improved by a factor of 4. The biostability of the nanocomposite hydrogel was also significantly improved compared with that of pure HAc hydrogels under both in vitro and in vivo conditions.
Electronic Conduction Mechanisms in BaTiO 3 –Ni Composites with Ultrafine Microstructure Obtained by Spark Plasma Sintering (2010)

Spark plasma sintering (SPS) was used to densify BaTiO 3 –Ni composite powders to relative densities above 92.8%. With the increasing Ni content, a decrease in relative density is observed, suggesting that Ni hampers the consolidation process. The microstructures of the BaTiO 3 –Ni composites were of duplex character. The crystallite size of the BaTiO 3 ‐grains was around 100 nm in average. The ceramic matrix phase of BaTiO 3 surrounded Ni inclusions of approximately 1 μm in diameter that were completely incorporated without the formation of any elongated metallic filaments. The ac conductivity of these BaTiO 3 –Ni composites increased with increasing Ni content and with temperature. The dominant conduction mechanisms in SPSed BaTiO 3 –Ni composites showed quite a complicated behavior. A gradual change from band conduction of trapped electrons in oxygen vacancies to a hopping‐type motion of small polarons between Ti 4+ and Ti 3+ is suggested to occur, when the Ni content increases. The influence of oxygen vacancies and other lattice defects on the electrical properties of BaTiO 3 –Ni composites is discussed.
Managing data quality by identifying the noisiest data samples (2012)

Enterprise datasets are often noisy. Several columns can have non-standard, erroneous or missing information. Poor quality data can lead to incorrect reporting and wrong conclusions being drawn. Data cleansing involves standardizing such data to improve its quality. Often data cleansing tasks involve writing rules manually. The step involves understanding the data quality issues and then writing data transformation rules to correct these issues. This is a human intensive task. In this study we propose a method to identify noisy subsets of huge unlabelled textual datasets. This is a two step process where in the first step we develop an estimation tool to predict the data quality on an unlabelled text dataset as produced by a segmentation model. The accuracy of the proposed method is shown on a real life dataset.
Effect of interleukin-1 (IL-1) blockade on cytokine synthesis: I. IL-1 receptor antagonist inhibits IL-1-induced cytokine synthesis and blocks the binding of IL-1 to its type II receptor on human monocytes (1992)

Interleukin-1 (IL-1) induces IL-1, tumor necrosis factor alpha (TNF alpha), and IL-6 gene expression and synthesis in a variety of cells. In this study, we investigated the ability of human recombinant IL-1 receptor antagonist (IL-1ra) to inhibit IL-1-induced cytokine production in human peripheral blood mononuclear cells (PBMC) and isolated monocytes. IL-1ra alone at concentrations as high as 1 microgram/mL did not induce IL-1 alpha, IL-1 beta, TNF alpha, or IL-6 synthesis. Suppression of IL-1-induced IL-1, TNF alpha, or IL-6 synthesis was dose-dependent (P less than or equal to .0001). At a twofold molar excess, IL-1ra inhibited IL-1-induced IL-1 or TNF alpha synthesis by 50% (P less than .01); an equimolar concentration of IL-1ra inhibited synthesis of these two cytokines by over 20% (P less than .05). A 10-fold molar excess of IL-1ra over IL-1 beta reduced IL-1 beta-induced IL-1 alpha by 95% (P = .01) and IL-1 alpha-induced IL-1 beta by 73% (P less than .01). IL-1ra added to PBMC 8 hours after stimulation with IL-1 beta was still able to inhibit IL-1 alpha, TNF alpha, and IL-6 synthesis (P less than or equal to .01). A similar reduction in IL-1 beta-induced IL-1 alpha was observed when IL-1 beta was removed from the cultures after 8 hours of stimulation (P less than .05), suggesting a prolonged presence of IL-1 or restimulation of IL-1 receptors on monocytes is required for the induction of cytokines. In elutriated monocytes, a 10-fold molar excess of IL-1ra reduced IL-1 beta-induced IL-1 alpha by 82% (P less than .05), TNF alpha by 64% (P = .05), and IL-6 by 47% (P less than .05). 125I-IL-1 beta was bound to purified monocytes, cross-linked, and immunoprecipitated. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed a band at 85 Kd corresponding to the 68-Kd IL-1 receptor type II (IL-1RtII). Excess unlabeled IL-1 beta or IL-1ra blocked the binding of 125I-IL-1 beta to the IL-1RtII. We conclude that IL-1ra inhibits IL-1-induced cytokine synthesis and competes with IL-1 for the IL-1RtII on human monocytes.
Diffusion of Atomic Hydrogen through V–Ni Alloy Membranes under Nondilute Conditions (2011)

Vanadium and other group V metals and alloys exhibit much higher hydrogen permeabilities than palladium alloys, and the basis of this lies primarily in their high hydrogen solubility. Because absorbed hydrogen profoundly influences the physical and chemical properties of the host metal, classical absorption and diffusion theories, which assume low concentrations of solute, may not apply to these alloys. To elucidate hydrogen transport through nondilute alloy membranes, a comprehensive series of absorption and flux measurements have been made for three V–Ni alloys over a range of pressures and temperatures. Alloy disks of three compositions (V95Ni5, V90Ni10, and V85Ni15 atom %) were sectioned from arc-melted ingots and coated on each side with a Pd dissociation catalyst. Hydrogen absorption and desorption isotherms were calculated using the Sieverts’ method, and hydrogen flux was measured using the constant-pressure permeation method. The pressure–concentration relationships of these alloys were nonideal, particularly at high hydrogen concentrations. As a result, the diffusion coefficients for each alloy exhibited a significant hydrogen concentration dependence, which illustrates the nonapplicability of Fick’s first law of diffusion to these alloys. A strong dependence on Ni content was also observed. During permeation the hydrogen concentration gradient increases with increasing distance from the feed surface.
Critical behavior of ferromagnetic perovskite ruthenates (2012)

Stoner-Wohlfarth itinerant-electron ferromagnetism has been believed to be applicable to the metallic, ferromagnetic perovskite SrRuO${}_{3}$. A key piece of evidence is the linearity of the Arrott plot ${M}^{2}$ versus $H/M$ obtained in a previous study. However, a typical Heisenberg behavior observed in isostructural BaRuO${}_{3}$ raises a question how the small structural change between them can place these compounds into two extremes of magnetic interactions. For clarification of this issue, we carried out magnetization measurements in the vicinity of ${T}_{\mathrm{c}}$ for the whole series of ferromagnetic ruthenates from Ca${}_{0.5}$Sr${}_{0.5}$RuO${}_{3}$ to SrRuO${}_{3}$ to BaRuO${}_{3}$. Moreover, we studied the effects of the $A$-site size variance and hydrostatic versus nonhydrostatic pressure on the Arrott plot of SrRuO${}_{3}$. Our results reveal that the magnetization behavior as presented by the Arrott plot is extremely sensitive to structural distortions. The linearity of the Arrott plot for SrRuO${}_{3}$ is actually part of a continuous curvature evolution as lattice distortions and spin-orbit coupling change; it may have little to do with Stoner-Wohlfarth itinerant-electron ferromagnetism. The data for these ruthenates point to a distinct phase appearing between localized-electron and broad-band behavior that exhibits a strong ferromagnetism stabilized by strong correlations among electrons of a narrow band.
Astronaut health monitoring (2006)

Extended weightlessness causes numerous deleterious changes in human physiology, including space motion sickness, cephalad fluid shifts, reduced immune response, and breakdown of muscle tissue with subsequent loss of bone mass and formation of renal stones. Furthermore, these physiological changes also influence the metabolism of drugs used by astronauts to minimize these deleterious effects. Unfortunately, the changes in human physiology in space are also reflected in drug metabolism, and current pre-flight analyses designed to set dosage are inadequate. Furthermore, current earth-based analytical laboratory methods that employ liquid or gas chromatography for separation and fluorescence or mass spectrometry for trace detection are labor intensive, slow, massive, and not cost-effective for operation in space. In an effort to overcome these instrument limitations we have been developing a sampling device to both separate these drugs and metabolites from urine, and generate surface-enhanced Raman (SER) spectra. The detailed molecular vibrational information afforded by Raman scattering allows chemical identification, while the surface-enhancement increases sensitivity by six or more orders of magnitude and allows detection of nanogram per milliliter concentrations. Generally no more than 1 milliliter of sample is required and complete analysis can be performed in 5 minutes using a portable, light-weight Raman spectrometer. Here we present the SER analysis of several drugs used by astronauts measured in synthetic urine and reconstituted urine.
Dissecting the Thermodynamics of ATP Binding to GroEL One Nucleotide at a Time (2022)

Abstract Understanding how large, oligomeric protein complexes respond to the binding of small ligands and other proteins is essential for describing the molecular basis of life. This in turn requires a complete characterization of the binding energetics and correlation of thermodynamic data with interacting structures, including effects of small molecules and solvent. However, the size of many protein oligomers, the myriad intermediate ligation states they can populate, and their often complex allosteric regulation typically restrict analysis by traditional methods to low resolution, ensemble averages. Here, we employ variabletemperature electrospray ionization native mass spectrometry to determine the thermodynamics for stepwise binding of up to ATP molecules to the 801 kDa GroEL complex, a tetradecamer chaperonin complex. Binding thermodynamics reveal strong enthalpy-entropy compensation (EEC) and high degrees of cooperativity are observed for formation of GroEL-ATP 7 and GroEL-ATP 14 . These are evidenced by entropically favored ATP binding to the cis ring (formation of GroEL-ATP 1-7 ), with variations in EEC for subsequent binding of ATP to the trans ring (GroEL-ATP 8-14 ), as expected for negative inter-ring cooperativity. Entropy driven ATP binding to the GroEL tetradecamer is consistent with ligand induced conformational changes of the GroEL tetradecamer, though the magnitude of the entropy change suggests that reorganization of GroEL-hydrating water molecules and/or expulsion of water from the GroEL cavity may also play a key role. By determining the thermodynamic signatures for individual ligand binding reactions to the large, nearly MDa GroEL complex, we expand our fundamental view of chaperonin functional chemistry. Moreover, this work and related studies of protein-ligand interactions illustrate unparalleled capabilities of vT-ESI-nMS for thermodynamics studies of protein interactions with ligands, and other molecules, such as proteins and drugs.
Progress in understanding mood disorders: optogenetic dissection of neural circuits (2013)

Major depression is characterized by a cluster of symptoms that includes hopelessness, low mood, feelings of worthlessness and inability to experience pleasure. The lifetime prevalence of major depression approaches 20%, yet current treatments are often inadequate both because of associated side effects and because they are ineffective for many people. In basic research, animal models are often used to study depression. Typically, experimental animals are exposed to acute or chronic stress to generate a variety of depression-like symptoms. Despite its clinical importance, very little is known about the cellular and neural circuits that mediate these symptoms. Recent advances in circuit-targeted approaches have provided new opportunities to study the neuropathology of mood disorders such as depression and anxiety. We review recent progress and highlight some studies that have begun tracing a functional neuronal circuit diagram that may prove essential in establishing novel treatment strategies in mood disorders. First, we shed light on the complexity of mesocorticolimbic dopamine (DA) responses to stress by discussing two recent studies reporting that optogenetic activation of midbrain DA neurons can induce or reverse depression-related behaviors. Second, we describe the role of the lateral habenula circuitry in the pathophysiology of depression. Finally, we discuss how the prefrontal cortex controls limbic and neuromodulatory circuits in mood disorders.
ChemInform Abstract: Surprisingly High Diastereoselection in the Aldol Reactions of Sodium Enolates of α‐Amino Methyl Ketones. (1994)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Advanced Nonlinear Finite Element Modelling of Reinforced Concrete Bridge Piers (2018)

Severe cracking was observed on the flexural tension face of a reinforced concrete hammerhead bridge pier cap. Determining the cause and severity of the damage was complicated by the geometry of the piers, which influenced the strut-and-tie mechanism. A tapered end cap raised questions about the development of the tension reinforcement in the chord, while a hexagonal pier column meant that the effective area of the compressive strut was uncertain. Depending on the assumptions made, widely different estimates of the ultimate capacity were reached by traditional calculation methods. Therefore, to accurately assess the safety of the bridge piers, a series of analyses were performed using VecTor2 – a nonlinear finite element analysis program (NLFEA) developed at the University of Toronto. A parametric study was conducted by varying the effective width of the piers and the amount of reinforcement engaged, and the factored strength of the pier was obtained using a novel procedure. This paper concludes that using 2-D NLFEA in a discerning manner allows engineers to understand complex 3-D situations.
Increased adhesiveness of peripheral blood leukocytes corresponds to the appearance of expansion following anterior wall myocardial infarction (1996)

The appearance of increased leukocyte adhesiveness/aggregation as an inflammatory marker in the peripheral blood of patients with anterior wall myocardial infarction was monitored. Of the 26 patients included in the study, 7 had infarct expansion as shown by an enlargement of left ventricular end-diastolic volume. The percent of aggregated leukocytes in the peripheral blood of patients with expansion (29.7 +/- 15.5%) was significantly higher (p = 0.01) than that obtained from patients with no expansion (18.5 +/- 6.8%). The lack of significant differences in peak creatine kinase concentrations between patients with and without expansion suggests that infarct size is not necessarily the main determinant for the appearance of expansion; an increased inflammatory reaction could be a contributory factor.
Abstract 15157: AT1 Receptor-Activated Toll-Like Receptor 4 in the Brainstem Causes Sympathoexcitation in Mice With Heart Failure (2010)

Background: Previous studies suggest that heart failure (HF) is associated with sympathoexcitation due to oxidative stress in the brain induced by AT1 receptors (AT1R). In the brain, oxidative stress occurs upstream of inflammatory signaling pathways mediated by toll-like receptor 4 (TLR4). Hypothesis: AT1R-induced sympathoexcitation is mediated by TLR4 in the brainstem of HF model , and if so, the inflammation in the brain is associated with sympathoexcitation. Method and Results: As a model of HF, the left coronary artery was ligated to induce a large myocardial infarction and subsequent HF in ICR mice. On day 10 after the left coronary artery ligation, we initiated 14-day chronic intracerebroventricular (ICV) infusion of losartan (CHF-Los) or vehicle (CHF-Veh) via osmotic minipumps. Expression of TLR4 in the brainstem determined by Western blot analysis was significantly higher in HF mice than in sham mice (1.06±0.04 vs 0.56±0.11, n=5 for each, P<0.05) and significantly lower in CHF-Los than in CHF-Veh...