gebhart/patrepeval huggingface dataset:
Properties of a New Group of Alkalophilic Bacteria (1980)

Five strains of a new alkalophilic bacterium have been isolated from potato-processing effluent. These strains are Gram-positive, non-sporing, motile rods which form an orange, cell-bound pigment and are capable of growth in aerobic or anaerobic conditions at a pH up to 11·5 and between 7 and 43°C. For one representative strain the highest growth rate occurred in the pH range 8 to 10·5 and the minimum doubling time observed was 27 min at approximately 38°C. With glucose as substrate, lactate, acetate and formate were major end-products, the proportions depending on cultural conditions.
Hepatic arterial injection chemotherapy with cisplatin suspended in an oily lymphographic agent for hepatocellular carcinoma (1989)

A method to prepare cisplatin suspended in an oily lymphographic agent, Lipiodol (LPS), has been established to deliver cisplatin to hepatocellular carcinoma (HCC) by the hepatic artery. Seventy-one patients, one Stage I, 16 Stage II, 16 Stage III, and 38 Stage IV, were treated with LPS therapy. A partial response was obtained in 33 cases (46.5%), a minor response in 20 cases (28.2%), and no change in 18 cases (25.3%). In 34 patients whose serum alpha-fetoprotein (AFP) levels were greater than 400 ng/ml, the serum AFP levels decreased in 31 patients (91.2%). The AFP decreased by more than 50% in 25 cases (73.5%) and more than 75% in 19 cases (55.9%). The plasma des-gamma-carboxy prothrombin (DCP) levels decreased in all of the 26 DCP-positive patients. The survival rate was 77% at 6 months and the 1-year survival rate was estimated to be 55%. The patients treated with LPS therapy survived longer compared with patients given Lipiodol containing neocarzinostatin by the hepatic artery. Complications such as acute gastroduodenal mucosal lesions (24%), cholecystitis (2.8%), pancreatitis (7%), delayed jaundice (7%), and hepatic encephalopathy (4.2%) were observed after therapy. The peak plasma platinum (Pt) concentrations determined as ultrafilterable Pt occurred 5 to 20 minutes, and 5 to 60 minutes as total Pt after the end of LPS injection. The Pt concentrations in the tumor tissues were 42 times higher in four operated cases and 7.1 times higher in six autopsy cases than those in the nontumorous tissue. These results suggest that LPS selectively accumulates in the HCC, is long-lasting and gradually releases the drug. In addition it is effective as a new anti-cancer therapy for hepatocellular carcinoma.
Computational signal-to-noise ratio analysis for optical quadrature microscopy (2009)

Optical quadrature microscopy (OQM) was invented in 1997 to reconstruct a full-field image of quantitative phase, and has been used to count the number of cells in live mouse embryos. Here we present a thorough SNR analysis that incorporates noise terms for fluctuations in the laser, aberrations within the individual paths of the Mach-Zehnder interferometer, and imperfections within the beamsplitters and CCD cameras to create a model for the resultant phase measurements. The current RMS error of the OQM phase images has been calculated to be 0.08 radians from substituting images from the instrumentation into the model.
Concise total synthesis of largazole (2010)

The concise total synthesis of largazole was accomplished. The key step included the use of the Nagao thiazolidinethione auxiliary for the diastereoselective acetate aldol reaction and it acts as an acylating agent for the peptide formation.
Apolipoprotein C-I Induces Apoptosis in Human Aortic Smooth Muscle Cells via Recruiting Neutral Sphingomyelinase (2003)

ApoC-I and apoC-I-enriched HDL activate the N-SMase-ceramide signaling pathway, leading to apoptosis in human ASMC, which is an effect that may promote plaque rupture in vivo.
Development and rescue of human familial hypercholesterolaemia in a xenograft mouse model (2015)

Diseases of lipid metabolism are a major cause of human morbidity, but no animal model entirely recapitulates human lipoprotein metabolism. Here we develop a xenograft mouse model using hepatocytes from a patient with familial hypercholesterolaemia caused by loss-of-function mutations in the low-density lipoprotein receptor (LDLR). Like familial hypercholesterolaemia patients, our familial hypercholesterolaemia liver chimeric mice develop hypercholesterolaemia and a 'humanized' serum profile, including expression of the emerging drug targets cholesteryl ester transfer protein and apolipoprotein (a), for which no genes exist in mice. We go on to replace the missing LDLR in familial hypercholesterolaemia liver chimeric mice using an adeno-associated virus 9-based gene therapy and restore normal lipoprotein profiles after administration of a single dose. Our study marks the first time a human metabolic disease is induced in an experimental animal model by human hepatocyte transplantation and treated by gene therapy. Such xenograft platforms offer the ability to validate human experimental therapies and may foster their rapid translation into the clinic.
The Atlantis Project: A GPS-Guided Wing-Sailed Autonomous Catamaran (2006)

ABSTRACT: An autonomous catamaran, based on a modified Prindle-19 day-sailing Catamaran, was built to test the viability of GPS-based system identification for precision control. The catamaran was fitted with several sensors and actuators to characterize the dynamics. Using an electric trolling motor, and lead ballast to match all-up weight, several system identification passes were performed to excite system modes and model the dynamic response. LQG controllers were designed based on the results of the system identification passes, and tested with the electric trolling motor. Line following performance was excellent, with cross track error standard deviations of less than 0.15 meters. The wing-sail propulsion system was fitted, and the controllers tested with the wing providing all forward thrust. Line following performance and disturbance rejection were excellent, with the cross track error standard deviations of approximately 0.30 meters, in spite of wind speed variations of over 50% of nominal value.
Synthesis and characterization of photoactivatable peptide agonists of the human thrombin receptor (1994)

Chemical synthesis and biochemical analysis of modified agonist peptides of the human thrombin receptor derived from the sequence SFLLRNP containing photoactivatable azido groups and biotin for sensitive detection is described. Substitution of leucine in position three with p-azidophenylalanine and extension of the C-terminus with a KGGK spacer containing biotin covalently linked to the side chain of the C-terminal lysine residue resulted in an active receptor agonist as determined by intracellular Ca2+ mobilization in human erythroleukemia (HEL) cells. In contrast, substitution of phenylalanine in position two with p-azidophenylalanine reduced agonist activity significantly.
Variable Guard Interval for OFDM based WLANs (2006)

The dynamic selection of guard interval in orthogonal frequency division multiplexing (OFDM) based wireless local area network (WLAN) systems is described in this work. It derives an algorithm and provides its performance merit for implementing variable guard interval (VGI). The proposed system improves mean, outage and maximum throughput significantly as compared to standard OFDM system using fixed guard interval without sacrificing bit error rate performance.
Design, Synthesis, and Antimicrobial Evaluation of a Novel Bone-Targeting Bisphosphonate-Ciprofloxacin Conjugate for the Treatment of Osteomyelitis Biofilms (2017)

Osteomyelitis is a major problem worldwide and is devastating due to the potential for limb-threatening sequelae and mortality. Osteomyelitis pathogens are bone-attached biofilms, making antibiotic delivery challenging. Here we describe a novel osteoadsorptive bisphosphonate-ciprofloxacin conjugate (BV600022), utilizing a "target and release" chemical strategy, which demonstrated a significantly enhanced therapeutic index versus ciprofloxacin for the treatment of osteomyelitis in vivo. In vitro antimicrobial susceptibility testing of the conjugate against common osteomyelitis pathogens revealed an effective bactericidal profile and sustained release of the parent antibiotic over time. Efficacy and safety were demonstrated in an animal model of periprosthetic osteomyelitis, where a single dose of 10 mg/kg (15.6 μmol/kg) conjugate reduced the bacterial load by 99% and demonstrated nearly an order of magnitude greater activity than the parent antibiotic ciprofloxacin (30 mg/kg, 90.6 μmol/kg) given in multiple doses. Conjugates incorporating a bisphosphonate and an antibiotic for bone-targeted delivery to treat osteomyelitis biofilm pathogens constitute a promising approach to providing high bone-antimicrobial potency while minimizing systemic exposure.
Metabolic and Antiproliferative Consequences of Activated Polyamine Catabolism in LNCaP Prostate Carcinoma Cells (2004)

Depletion of intracellular polyamine pools invariably inhibits cell growth. Although this is usually accomplished by inhibiting polyamine biosynthesis, we reasoned that this might be more effectively achieved by activation of polyamine catabolism at the level of spermidine/spermine N(1)-acetyltransferase (SSAT); a strategy first validated in MCF-7 breast carcinoma cells. We now examine the possibility that, due to unique aspects of polyamine homeostasis in the prostate gland, tumor cells derived from it may be particularly sensitive to activated polyamine catabolism. Thus, SSAT was conditionally overexpressed in LNCaP prostate carcinoma cells via a tetracycline-regulatable (Tet-off) system. Tetracycline removal resulted in a rapid approximately 10-fold increase in SSAT mRNA and an increase of approximately 20-fold in enzyme activity. SSAT products N(1)-acetylspermidine, N(1)-acetylspermine, and N(1),N(12)-diacetylspermine accumulated intracellularly and extracellularly. SSAT induction also led to a growth inhibition that was not accompanied by polyamine pool depletion as it was in MCF-7 cells. Rather, intracellular spermidine and spermine pools were maintained at or above control levels by a robust compensatory increase in ornithine decarboxylase and S-adenosylmethionine decarboxylase activities. This, in turn, gave rise to a high rate of metabolic flux through both the biosynthetic and catabolic arms of polyamine metabolism. Treatment with the biosynthesis inhibitor alpha-difluoromethylornithine during tetracycline removal interrupted flux and prevented growth inhibition. Thus, flux-induced growth inhibition appears to derive from overaccumulation of metabolic products and/or from depletion of metabolic precursors. Metabolic effects that were not excluded as possible contributing factors include high levels of putrescine and acetylated polyamines, a 50% reduction in S-adenosylmethionine, and a 45% decline in the SSAT cofactor acetyl-CoA. Overall, the study demonstrates that activation of polyamine catabolism in LNCaP cells elicits a compensatory increase in polyamine biosynthesis and downstream metabolic events that culminate in growth inhibition.
Enhanced inactivation and acceleration of activation of the sodium channel associated with epilepsy in man (2001)

Generalized epilepsy with febrile seizures-plus (GEFS+) is a benign Mendelian syndrome characterized by childhood-onset febrile and afebrile seizures. Three point mutations within two voltage-gated sodium channel genes have been identified so far: in GEFS+ type 1 a mutation in the beta1-subunit gene SCN1B, and in GEFS+ type 2 two mutations within the neuronal alpha-subunit gene SCN1A. Functional expression of the SCN1B and one of the SCN1A mutations revealed defects in fast channel inactivation which are in line with previous findings on myotonia causing mutations in SCN4A, the skeletal muscle sodium channel alpha-subunit gene, all showing an impaired fast inactivation. We now studied the second GEFS+ mutation (T875M in SCN1A), using the highly homologous SCN4A gene (mutation T685M). Unexpectedly, the experiments revealed a pronounced enhancement of both fast and slow inactivation and a defect of channel activation for T685M compared to wild-type channels. Steady-state fast and slow inactivation curves were shifted in the hyperpolarizing direction, entry into slow inactivation was threefold accelerated, recovery from slow inactivation was slowed by threefold and the time course of activation was slightly but significantly accelerated. In contrast to other disease-causing mutations in SCN1A, SCN1B and SCN4A, the only mechanism that could explain hyperexcitability of the cell membrane would be the acceleration of activation. Because the enhancement of slow inactivation was the most obvious alteration in gating found for T685M, this might be the disease-causing mechanism for that mutation. In this case, the occurrence of epileptic seizures could be explained by a decrease of excitability of inhibitory neurons.
The Evolution of the Granodioritic Rocks of the South-Eastern End of the Kopaonik Batholith, Yugoslavia (1938)

Summary and Conclusions The composite granodiorite batholith of the Kopaonik Mountains forms one of the more southerly members of the peri-Adriatic tonalitic intrusions. In the area discussed in this paper it intrudes a series of sedimentary rocks which range from dominantly calcareous to pelitic types. Metamorphism of these rocks has produced crystalline limestones, skarns, and calc-silicate hornfelses, which grade downwards into mica-, amphibole-, epidote-, and locally cordierite-bearing rocks. The pelitic and amphibole-bearing hornfelses are in immediate proximity to the batholith on the surface. The amphibole-bearing types are mainly confined to a relatively small area, well within the zone of high-grade metamorphism and overlying the southerly pitching nose of the intrusion. With them are associated hornfelses which carry porphyroblasts of albitic feldspar. It appears that the persistence of the amphibole and the development of these feldspar porphyroblasts may have been caused by hydrous and probably sodic emanations which permeated the sediments above and ahead of the advancing igneous mass.
Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1–induced pruritus (2014)

In humans, pruritus (itch) is a common but poorly understood symptom in numerous skin and systemic diseases. Endothelin 1 (ET-1) evokes histamine-independent pruritus in mammals through activation of its cognate G protein-coupled receptor endothelin A receptor (ETAR). Here, we have identified neural endothelin-converting enzyme 1 (ECE-1) as a key regulator of ET-1-induced pruritus and neural signaling of itch. We show here that ETAR, ET-1, and ECE-1 are expressed and colocalize in murine dorsal root ganglia (DRG) neurons and human skin nerves. In murine DRG neurons, ET-1 induced internalization of ETAR within ECE-1-containing endosomes. ECE-1 inhibition slowed ETAR recycling yet prolonged ET-1-induced activation of ERK1/2, but not p38. In a murine itch model, ET-1-induced scratching behavior was substantially augmented by pharmacological ECE-1 inhibition and abrogated by treatment with an ERK1/2 inhibitor. Using iontophoresis, we demonstrated that ET-1 is a potent, partially histamine-independent pruritogen in humans. Immunohistochemical evaluation of skin from prurigo nodularis patients confirmed an upregulation of the ET-1/ETAR/ECE-1/ERK1/2 axis in patients with chronic itch. Together, our data identify the neural peptidase ECE-1 as a negative regulator of itch on sensory nerves by directly regulating ET-1-induced pruritus in humans and mice. Furthermore, these results implicate the ET-1/ECE-1/ERK1/2 pathway as a therapeutic target to treat pruritus in humans.
Hospital rules-based system: The next generation of medical informatics for patient safety (2005)

The HRBS enhances the identification of drug-related problems while optimizing patient care and improving communication and efficiency at a major medical center.
Predicting Regional Mutability in Antibody V Genes Based Solely on Di- and Trinucleotide Sequence Composition (1999)

Somatic mutations are not distributed randomly throughout Ab V region genes. A sequence-specific target bias is revealed by a defined hierarchy of mutability among di- and trinucleotide sequences located within Ig intronic DNA. Here we report that the di- and trinucleotide mutability preference pattern is shared by mouse intronic JH and Jkappa clusters and by human VH genes, suggesting that a common mutation mechanism exists for all Ig V genes of both species. Using di- and trinucleotide target preferences, we performed a comprehensive analysis of human and murine germline V genes to predict regional mutabilities. Heavy chain genes of both species exhibit indistinguishable patterns in which complementarity-determining region 1 (CDR1), CDR2, and framework region 3 (FR3) are predicted to be more mutable than FR1 and FR2. This prediction is borne out by empirical mutation data from nonproductively rearranged human VH genes. Analysis of light chain genes in both species also revealed a common, but unexpected, pattern in which FR2 is predicted to be highly mutable. While our analyses of nonfunctional Ig genes accurately predicts regional mutation preferences in VH genes, observed relative mutability differences between regions are more extreme than expected. This cannot be readily accounted for by nascent mRNA secondary structure or by a supplemental gene conversion mechanism that might favor nucleotide replacements in CDR. Collectively, our data support the concept of a common mutation mechanism for heavy and light chain genes of mice and humans with regional bias that is qualitatively, but not quantitatively, accounted for by short nucleotide sequence composition.
Stable Planar Six-π-Electron Six-Membered N-Heterocyclic Carbenes with Tunable Electronic Properties (2005)

Carbene analogues of borazines are highly thermally stable. Keeping quasi-identical steric demands, the electronic properties of the carbene can be precisely tuned by varying the nature of the substituents at the boron centers.
Integrated CO<sub>2</sub> Capture, Conversion, and Storage To Produce Calcium Carbonate Using an Amine Looping Strategy (2018)

One of the critical and emerging needs for sustainable energy production is the development of novel integrated approaches for the capture, conversion, and storage of CO2. In this context, carbon mineralization, which is a thermodynamically downhill route for the accelerated conversion of CO2 to water-insoluble and stable calcium and magnesium carbonates, is a sustainable approach for permanently storing CO2. However, one of the challenges with carbon mineralization has been the need for higher concentrations of CO2 to accelerate the formation of calcium and magnesium carbonates. In this study, we propose a direct integrated approach in which amine-bearing solvents, such as monoethanolamine (MEA), and alkaline Ca-bearing solids, such as calcium oxide and calcium silicate, are reacted in a slurry reaction system in two modes. These two modes involve in situ changes in the aqueous chemistry to facilitate the capture of CO2 using MEA and the release of CO2 into the aqueous phase to produce higher conversions of calcium carbonate. In the first mode, continuous CO2 flow at 1 atm is provided such that MEA in the aqueous phase captures CO2 and supplies the captured carbon-bearing species for reaction with dissolved calcium. In the second mode, MEA pre-loaded with CO2 was introduced into the system without a continuous supply of CO2. Complete conversion of calcium oxide to calcium carbonate was achieved using both modes. Further, the extent of carbon mineralization achieved with calcium silicate was 36% in mode 1 as opposed to 20% in mode 2 at 50 °C for a reaction time of 3 h. These data suggested that amine-bearing solvents undergo continuous looping between the CO2-loaded and release states, which facilitate the accelerated conversion of calcium-bearing oxides and silicates to calcium carbonate. The formation of calcium carbonate and calcium hydroxide phases was noted when less than complete conversions of calcium oxide were achieved. Calcium carbonate was the only phase formed on the complete conversion of calcium oxide and the carbon mineralization of carbon dioxide.
Elucidating the Role of Microstructure, Texture, and Microtexture on the Dwell Fatigue Response of Ti-6Al-4V (2016)

Ambient temperature dwell sensitivity is known to be deleterious to the fatigue response of near-alpha titanium alloys. Dwell fatigue refers to the presence of a sustained hold at peak stress as opposed to the continuous variation of normal cyclic fatigue loading. This reduction in failure life-times from dwell loading is attributed to early crack nucleation and faster crack propagation. The degradation is the result of plastic anisotropy on the microstructural scale along with tendency of titanium alloys to creep at low temperatures at stresses well below the 0.2% offset yield strength. Despite being the most widely used titanium alloy, Ti-6Al-4V has not been the subject of most dwell fatigue research. Generally, dwell sensitivity is microstructurally dependent and believed to only affect Ti-6Al-4V when severe crystallographic texture is present and under high peak stress loading. Recent studies, however, have suggested that small clusters of preferred crystal orientations, known as micro-textured regions (MTR), can have a significant effect on the dwell sensitivities in Ti-6Al-4V even without severe overall texture in the material. In this study, smooth-bar fatigue specimens were subjected to uniaxial fatigue at 20 Hz cyclic and 2-min dwell loading conditions under load-control at stresses representative of service conditions, until failure occurred. A reduction in specimen life-times by approximately a factor of three was observed under dwell conditions, which was less than for the highly susceptible near-a titanium alloys such as Ti-6Al-2Sn-4Zr-2Mo, where the dwell debit is often in excess of a factor of ten. Measurement of fatigue and dwell fatigue crack growth rates revealed a significant acceleration of the dwell crack growth rates in certain cases. Backscattered electron imaging and electron backscattered diffraction were utilized to quantify the interaction between the cracks and local microstructure. Though no correlation was found between crack growth rate and the local microstructure and crack trajectory, strong correlation was found between crack growth and the presence of grains with [0001] axes at small angles (
Silver‐Ruthenium Dioxide Contacts (1976)

This paper describes the development of a novel electrical contact material, silver‐ruthenium oxide, for use in light duty switching applications where low contact resistance values must be maintained. Material fabrication and contact resistance behaviour after exposure to a tarnishing atmosphere are described. An explanation for the low contact resistance values obtained for silver‐ruthenium dioxide in comparison with pure silver is offered.