gebhart/patrepeval huggingface dataset:
Familial glucocorticoid resistance caused by a splice site deletion in the human glucocorticoid receptor gene. (1993)

The clinical syndrome of generalized, compensated glucocorticoid resistance is characterized by increased cortisol secretion without clinical evidence of hyper- or hypocortisolism, and manifestations of androgen and/or mineralocorticoid excess. This condition results from partial failure of the glucocorticoid receptor (GR) to modulate transcription of its target genes. We studied the molecular mechanisms of this syndrome in a Dutch kindred, whose affected members had hypercortisolism and approximately half of normal GRs, and whose proband was a young woman with manifestations of hyperandrogenism. Using the polymerase chain reaction to amplify and sequence each of the nine exons of the GR gene alpha, along with their 5'- and 3'-flanking regions, we identified a 4-base deletion at the 3'-boundary of exon 6 in one GR allele (delta 4), which removed a donor splice site in all three affected members studied. In contrast, the sequence of exon 6 in the two unaffected siblings was normal. A single nucleotide substitution causing an amino acid substitution in the amino terminal domain of the GR (asparagine to serine, codon 363) was also discovered in exon 2 of the other allele (G1220) in the proband, in one of her affected brothers and in her unaffected sister. The functional importance of this mutation was tested in a cotransfection study using the recombinant expression vector pRShGR-Ser363 and the glucocorticoid responsive vector mouse mammary tumor virus-chloramphenicol transferase. This amino acid substitution did not alter the function of the glucocorticoid receptor. Using reverse transcription-polymerase chain reaction we could only identify messenger RNA transcripts of the G1220-allele but not of the delta 4-allele in the affected members of this family who were heterozygous for the G1220 mutation. This deletion in the glucocorticoid receptor gene was, thus, associated with the expression of only one allele and a decrease of GR protein by 50% in affected members of this glucocorticoid resistant family. The mutation identified in exon 2 did not segregate with the disease and appears to be of no functional significance. The presence of the null allele was apparently compensated for by increased cortisol production at the expense of concurrent hyperandrogenism.
Decrease in intravenous antibiotic use with adjunctive aerosolized amikacin treatment in intubated mechanically ventilated patients with Gram-negative pneumonia (2007)

Hydrogen sulfide is produced endogenously by a variety of enzymes involved in cysteine metabolism. Clinical data indicate that endogenous levels of hydrogen sulfide are diminished in various forms of cardiovascular diseases. The aim of the current study was to investigate the effects of hydrogen sulfide supplementation on cardiac function during reperfusion in a clinically relevant experimental model of cardiopulmonary bypass. Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 minutes of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6), or the sodium sulfide infusion (1 mg/kg/hour, n = 6). Biventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and pulmonary blood flow, vasodilator responses to acetylcholine and sodiumnitroprusside and pulmonary function were also determined. Administration of sodium sulfide led to a significantly better recovery of left and right ventricular systolic function (P < 0.05) after 60 minutes of reperfusion. Coronary blood flow was also significantly higher in the sodium sulfide-treated group (P < 0.05). Sodium sulfide treatment improved coronary blood flow, and preserved the acetylcholine-induced increases in coronary and pulmonary blood (P < 0.05). Myocardial ATP levels were markedly improved in the sulfide-treated group. Thus, supplementation of sulfide improves the recovery of myocardial and endothelial function and energetic status after hypothermic cardiac arrest during cardiopulmonary bypass. These beneficial effects occurred without any detectable adverse hemodynamic or cardiovascular effects of sulfide at the dose used in the current study.
Construction of a restriction-less, marker-less mutant useful for functional genomic and metabolic engineering of the biofuel producer Clostridium acetobutylicum (2016)

The restriction-less, marker-less strain described in this study, as well as the maker-less genetic exchange coupled with positive selection, will be useful for functional genomic studies and for the development of industrial strains for the production of biofuels and bulk chemicals.
Olanzapine treatment in patients with typical and atypical neuroleptic-associated agranulocytosis (1998)

Two cases are reported of patients who developed agrunulocytosis after treatment with typical and atypical antipsychotics. The patients were successfully treated with olanzapine. We surest the consideration of olanzapine as a safer treatment in patients who require immediate continuation of antipsychotic medication and have a prior history of classic and atypical neuroleptic-induced agranulocytosis.
A hetero-oligomeric remorin-receptor complex regulates plant development (2021)

Abstract Plant growth and development are modulated by both biotic and abiotic stress. Increasing evidence suggests that cellular integration of the corresponding signals occurs within preformed hubs at the plasma membrane called nanodomains. These membrane sub-compartments are organized by multivalent molecular scaffold proteins, such as remorins. Here, we demonstrate that Group 1 remorins form a hetero-oligomeric complex at the plasma membrane. While these remorins are functionally redundant for some pathways their multivalency also allows the recruitment of specific interaction partners. One of them, the receptor-like kinase REMORIN-INTERACTING RECEPTOR 1 (RIR1), that acts redundantly with the closely related receptor NILR2, is specifically recruited by REM1.2 in a phosphorylation-dependent manner. Overlapping developmental phenotypes suggest that the REM/RIR complex regulates key developmental pathways.
Radical Instability in Aid of Efficiency: A Powerful Route to Highly Functional MIDA Boronates (2015)

The inability of the sp(3) boron in MIDA boronates to stabilize an adjacent radical makes possible the efficient addition of a wide array of xanthates to vinyl MIDA boronate, leading to highly functionalized and diverse aliphatic organoboron structures. The lack of radical stabilization also allows the exchange of the xanthate in the adducts with a bromine. In one case, the bromine was substituted to generate a cyclopropyl MIDA derivative.
CHAPTER 10. Materials Processing and Recycling with Near- and Supercritical CO2-based Solvents (2018)

This chapter describes one area of applications where supercritical CO2 (scCO2) is effectively used as a solvent. CO2-based solvents can be used to perform physical or chemical transformations, the two main routes introduced in this chapter to prepare advanced materials. For processes based on physical transformations, CO2 can be used as a solvent, antisolvent or as a solute for the controlled design of organic particles. Switching from physical to chemical transformations gives access to the design of advanced inorganic materials, such as nanopowders or films using supercritical CO2-based solvent systems. The choice of the reactor technology allows working with homogeneous (continuous reactor) or heterogeneous nucleation (cold wall reactor). With a continuous reactor, it is possible to synthesise metal or metal oxide nanoparticles. Changing to a cold wall reactor allows for the deposition of thin films (metals or metal oxides) on different kinds of substrates, i.e. the Supercritical Fluid Chemical Deposition (SFCD) process forming continuous, conformal and dense coatings. The SFCD technology has also been used for the deposition of heterostructures on other supports, such as silica beads, carbon nanotubes, carbon aerogels, etc., in hot-walled batch reactors. A more recent application of CO2-based solvents is in the field of materials recycling. scCO2 is very interesting as it can easily contribute to improving processes, e.g. in terms of metal leaching, by shortening their duration. It can also be included in current recycling processes as a supplementary step, as shown for lithium ion battery electrolyte extraction or printed circuit board delamination.
Structure‐Property Relationships in Waspaloy via Small Angle Scattering and Electrical Resistivity Measurements (2010)

The mechanical properties in superalloys are controlled by the distribution of the {gamma}{prime} precipitate phase. Electrical measurements have been shown to be sensitive to certain aspects of the precipitation process and show promise for predicting the evolving microstructural state in superalloys. Aging experiments were conducted on Waspaloy samples for temperatures between 600 and 950 C for times ranging from 2min to 500h. Particle size distributions were obtained by modeling of small angle scattering (SAS) data, whereas, small precipitate size information, strain, and lattice mismatch data were obtained from X-ray diffraction. The microstructural information was then used to create a figure of merit of electron scattering intended to correlate electrical properties to the precipitate microstructure. The proposed figure of merit shows an empirical correlation with the electrical resistivity data, demonstrating the sensitivity of the resistivity measurements to the precipitation process and coarsening behavior.
Autonomous DNA replication in human cells is affected by the size and the source of the DNA. (1991)

We previously developed short-term and long-term assays for autonomous replication of DNA in human cells. This study addresses the requirements for replication in these assays. Sixty-two random human genomic fragments ranging in size from 1 to 21 kb were cloned in a prokaryotic vector and tested for their replication ability in the short-term assay. We found a positive correlation between replication strength and fragment length, indicating that large size is favored for efficient autonomous replication in human cells. All large fragments replicated efficiently, suggesting that signals which can direct the initiation of DNA replication in human cells are either very abundant or have a low degree of sequence specificity. Similar results were obtained in the long-term assay. We also used the same assays to test in human cells a random series of fragments derived from Escherichia coli chromosomal DNA. The bacterial fragments supported replication less efficiently than the human fragments in the short-term and long-term assays. This result suggests that while the sequence signals involved in replication in human cells are found frequently in human DNA, they are uncommon in bacterial DNA.
Effect of Pore Size in Three Dimensionally Ordered Macroporous Polyimide Separator on Lithium Deposition/Dissolution Behavior (2019)

Li dendrite formation has disturbed the usage of Li metal anode in rechargeable battery. Three dimensionally ordered macroporous polyimide (3DOM PI) separator is one of possible technology to suppress the dendrite formation. In order to optimize porous structure, an effect of pore size in 3DOM PI separator was investigated using three different pore size for separator (300 nm, 500 nm, 800 nm). An ionic conductivity of separator depended on size of pore. With decreasing pore size, the ionic conductivity of separator increased. Li | Cu cell was employed to investigate an effect of pore size on morphology of lithium metal. 3DOM separator provided a uniform deposition of lithium metal and a suppression of dendrite formation. This is due to more uniform current distribution in 3DOM PI separator. The highest cycleability of lithium metal anode was realized by using smallest pore size 3DOM PI separator (300 nm). This is also related to uniform current distribution in the cell.
Precise Design of Artificial Cofactors for Enhancing Peroxidase Activity of Myoglobin: Myoglobin Mutant H64D Reconstituted with a “Single‐Winged Cofactor” Is Equivalent to Native Horseradish Peroxidase in Oxidation Activity (2011)

Abstract H64D myoglobin mutant was reconstituted with two different types of synthetic hemes that have aromatic rings and a carboxylate‐based cluster attached to the terminus of one or both of the heme‐propionate moieties, thereby forming a “single‐winged cofactor” and “double‐winged cofactor,” respectively. The reconstituted mutant myoglobins have smaller K m values with respect to 2‐methoxyphenol oxidation activity relative to the parent mutant with native heme. This suggests that the attached moiety functions as a substrate‐binding domain. However, the k cat value of the mutant myoglobin with the double‐winged cofactor is much lower than that of the mutant with the native heme. In contrast, the mutant reconstituted with the single‐winged cofactor has a larger k cat value, thereby resulting in overall catalytic activity that is essentially equivalent to that of the native horseradish peroxidase. Enhanced peroxygenase activity was also observed for the mutant myoglobin with the single‐winged cofactor, thus indicating that introduction of an artificial substrate‐binding domain at only one of the heme propionates in the H64D mutant is the optimal engineering strategy for improving the peroxidase activity of myoglobin.
Valorisation of mixtures of linear alkenes using cobalt-mediated isomerisation and hydroformylation chemistries (2022)

Active catalysts derived from cobalt and the Xantphos ligand were synthesised, characterised and tested in the hydroformylation of pure linear alkenes or their mixtures.
Ultrasound-microbubble-mediated drug delivery efficacy and cell viability depend on microbubble radius and ultrasound frequency (2010)

We have been investigating ultrasound-mediated drug delivery from microbubbles (MBs) as an alternative therapy to reduce hyper-proliferation of smooth muscle cells. We sought to determine if MB size affects drug delivery, cell viability, or cell adherence. Control, Dil, and drug-incorporated-rapamycin microbubbles (R-MBs) were size sorted into "small" and "large" sub-populations with number-average mean diameters of 1.7μm and 3.7μm respectively. Drug dose was maintained by keeping the surface area between MB sub-populations constant. Vascular smooth muscle cells (SMCs) were exposed to size-sorted R-MBs and insonated at 1MHz, 300 kPa, with 50 cycle sinusoids at a PRF of 100Hz for 8s. Insonation with large MBs reduced the proliferation rate of cells by 66.0% vs. 56.1% (n=8, p=0.46) with small MBs. The LIVE/DEAD® Viability/Cytotoxicity assay revealed a significant reduction in live cells (61.% live vs. 77.6% live), n=4, p=0.41), and a greater, but not statistically significant, increase in the permeabilized cells after insonation (1MHz) with large MBs (15.6%) versus small MBs (11.1%). We also investigated the effect of ultrasound frequency (1, 2.25, 5, and 10MHz) on MB on rupture and viability following 20 ultrasound pulses (20 cycle-sinusoids) at a peak negative pressure 600 kPa. 1MHz insonation ruptured the most microbubbles of either size, permeabilized the most cells (50% & 43% for small and large MBs respectively) and killed (33% & 31%) the most cells. More small (d = 1.8 μm) MBs were ruptured at every frequency (p<;0.001, see Fig. 4). Permeabilization of cells was approximately inversely related to frequency of insonation. 1MHz ultrasound permeabilized the most cells, but also killed the most cells. The permeable/dead cell ratio was 64% for large MBs and 98% for small MBs indicating a better therapeutic ratio when using small MBs.
Ammonium exposure and pyruvate affect the amino acid metabolism of bovine blastocysts in vitro (2004)

The accumulation of ammonium is a major artefact of in vitro embryo culture. This study has examined ammonium production and potential mechanisms of disposal in preimplantation bovine blastocysts. Embryos were produced by in vitro maturation and fertilisation of oocytes, and cultured in synthetic oviduct fluid containing amino acids and BSA (SOFaaBSA). Ammonium/urea concentrations were determined enzymatically. Amino acid appearance/disappearance 'profiles' of single blastocysts were determined at 0, 1.25 and 2.5 mM NH(4)Cl (with or without 0.33 mM pyruvate), and with or without 10 mM dipicolinic acid (DPCA; a glutamate dehydrogenase (GLDH) inhibitor) or 2 mM amino-oxyacetate (AOA; a transaminase inhibitor). Free ammonium was produced at a rate of 4.281 (+/-0.362) pmol/embryo/h, while urea production was undetectable. The presence/absence of pyruvate affected amino acid profiles, especially alanine appearance (P < 0.001), glutamate disappearance (P < 0.05) and overall turnover (the sum of appearance and disappearance) (P < 0.001). GLDH inhibition with DPCA had no effect on amino acid overall disappearance, but glutamate disappearance increased, while that of arginine decreased (P < 0.05). The transaminase inhibitor, AOA, depressed turnover (P < 0.05), aspartate and glutamate disappearance, and alanine appearance. Thus, bovine blastocysts release ammonium as free ions or fix them, not as urea, but as alanine, possibly glutamine and, less likely, arginine. An active role for GLDH and transaminases in regulating blastocyst amino acid metabolism was demonstrated.
Combinaisons nouvelles de Pezizales (2017)

Proposal of new combinations of some pezizalean species. Galactinia hypoleuca is combined in the genus Peziza Fr. s. lato, and illustrated microscopically after the revision of the holotype; Pachyphloeus oleiferus is combined in the genus Pachyphlodes Zobel; Pulvinula ovalispora is combined in the genus Boubovia Svrček; and Aleuria latispora is combined in the genus Melastiza Boud. Comments are provided for each species
A Technique to Visualize Tranparent Oil Using Pulsed Fluorescence Method (1998)

Anew technique to visualize transparent oil remotelyhasbeenpresented. Inherently a semiconductor-based oil sensor or a CCD-camera-based sensing device has been employed in a power plant. However, they can hardly recognize oil-leaked areas and issue a leak alarm immediately when monitoring transparent oil such as steam turbine oil and gas turbine oil. To overcome the restrictions, a pulsed fluorescence method, where a pulsed flash lamp is used for incident ultra violet ray in a standard fluorescence method, has been developed. For verification, an oil monitoring device based on the present technique has been developed. Some experiments to demonstrate performances of the present device have been carried out in an actual power plant. As a result, it has been shown that the present device works successfully.
African Swine Fever Virus Isolate, Georgia, 2007 (2008)

African swine fever (ASF) is widespread in Africa but is rarely introduced to other continents. In June 2007, ASF was confirmed in the Caucasus region of Georgia, and it has since spread to neighboring countries. DNA fragments amplified from the genome of the isolates from domestic pigs in Georgia in 2007 were sequenced and compared with other ASF virus (ASFV) isolates to establish the genotype of the virus. Sequences were obtained from 4 genome regions, including part of the gene B646L that encodes the p72 capsid protein, the complete E183L and CP204L genes, which encode the p54 and p30 proteins and the variable region of the B602L gene. Analysis of these sequences indicated that the Georgia 2007 isolate is closely related to isolates belonging to genotype II, which is circulating in Mozambique, Madagascar, and Zambia. One possibility for the spread of disease to Georgia is that pigs were fed ASFV-contaminated pork brought in on ships and, subsequently, the disease was disseminated throughout the region.
Myelodysplastic syndromes/myeloproliferative overlap neoplasms (2020)

The myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are haematologically diverse stem cell malignancies sharing phenotypic features of both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) that display a paradoxical bone marrow phenotype hallmarked by myeloid proliferation in the context of bone marrow dysplasia and ineffective haematopoiesis. The unfolding MDS/MPN genomic landscape has revealed numerous mutations in signalling genes, such as <italic>CBL, JAK2, NRAS, KRAS, CSF3R</italic>, and others involving the spliceosome complex. These observations suggest that comutation of genes involved in dysplasia and bone marrow failure along with those of cytokine receptor signalling may, in part, explain the dual MDS/MPN phenotype. The respective MDS/MPN diseases are identified by the type of myeloid subset which predominates in the peripheral blood. Currently there are no standard treatment recommendations for most patients with MDS/MPN. To optimize efforts to improve the management and disease outcomes, it is essential to identify meaningful clinical and biologic endpoints and standardized response criteria for clinical trials.
Changes in Auditory P3 Event-related Potential in Schizophrenia and Depression (1987)

Event-related potentials during a two-tone discrimination task were recorded in 24 schizophrenic patients, 16 depressed patients and 59 control subjects. Recordings were made when patients were medication-free. Fourteen schizophrenic and 13 depressed patients were retested at 1 and 4 weeks after the start of treatment, and 13 schizophrenic patients were also tested between 6 and 24 months after the initial recordings. In the schizophrenic group, the P3 latency was significantly prolonged compared with that in the control and the depressed groups, and remained unchanged both after 4 weeks treatment with therapeutic doses of neuroleptic drugs and at long-term follow-up. In the depressed group, the P3 latency did not differ from that of controls. P3 amplitude by contrast was reduced in both the acutely depressed and schizophrenic groups and following treatment became normal in the depressed group but remained reduced in the schizophrenic group. It is suggested that a prolonged P3 latency and reduced P3 amplitude indicate an impairment of auditory information processing in some patients with schizophrenia which is independent of the presence of acute psychotic symptoms and is not influenced by neuroleptic medication.
Towards automating code review at scale (2021)

As neural methods are increasingly used to support and automate software development tasks, code review is a natural next target. Yet, training models to imitate developers based on past code reviews is far from straightforward: reviews found in open-source projects vary greatly in quality, phrasing, and depth depending on the reviewer. In addition, changesets are often large, stretching the capacity of current neural models. Recent work reported modest success at predicting review resolutions, but largely side-stepped the above issues by focusing on small inputs where comments were already known to occur. This work examines the vision and challenges of automating code review at realistic scale. We collect hundreds of thousands of changesets across hundreds of projects that routinely conduct code review, many of which change thousands of tokens. We focus on predicting just the locations of comments, which are quite rare. By analyzing model performance and dataset statistics, we show that even this task is already challenging, in no small part because of tremendous variation and (apparent) randomness in code reviews. Our findings give rise to a research agenda for realistically and impactfully automating code review.