gebhart/patrepeval huggingface dataset:
Hemodynamic Effects of a New Inotropic Compound, PST-2744, in Dogs With Chronic Ischemic Heart Failure (2003)

Inotropic agents for acute decompensated heart failure are associated with a lack of efficacy or increased mortality. New compounds are needed to support patients with acute exacerbations of heart failure. This study examined the hemodynamic effects of a new inotropic agent (PST-2744) in dogs with chronic ischemic heart failure. Eight mongrel dogs at low risk for postmyocardial infarction (MI) sudden death entered the protocol. Dogs were studied after ischemic left ventricular dysfunction was induced by repeated injections of latex microspheres into the circumflex artery until the ejection fraction reached 35%. Hemodynamic parameters were measured at baseline and peak drug effect (PST-2744 5 microg.kg-1.min-1). In 5 animals, PST-2744 effects were compared with dobutamine. Heart rates, PR intervals and QT intervals were unchanged following PST-2744 administration. PST-2744 increased contractility (+dP/dt) by 56% from 1881 +/- 282 mm Hg/s to 2939 +/- 734 mm Hg/s (P < 0.01). The inotropic effect of PST-2744 was equal to that produced by 5-microg.kg-1.min-1 dobutamine (56% increase in +dP/dt), but peak heart rates were significantly higher with dobutamine (129 +/- 24 bpm PST-2744 versus 160 +/- 6 bpm 5-microg.kg-1.min-1 dobutamine, P < 0.002). No arrhythmias or conduction delays were seen with either compound. PST-2744 is an effective inotropic agent without positive chronotropic effect in subjects with stable moderate left ventricular dysfunction.
A Phase 1/2 Study of SKI-606, a Dual Inhibitor of Src and Abl Kinases, in Adult Patients with Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia (CML) or Acute Lymphocytic Leukemia (ALL) Relapsed, Refractory or Intolerant of Imatinib. (2006)

Abstract SKI-606 is an orally available, dual Src/Abl kinase inhibitor shown to be 200-fold more potent than imatinib as an inhibitor of Bcr-Abl phosphorylation in biochemical assays. BaF3 cell lines and primary cells from pts expressing different imatinib-resistant Bcr-Abl mutant proteins are sensitive to SKI-606 in vitro. Unlike imatinib and dasatinib, SKI-606 exhibits no significant inhibition of c-kit or PDGFR. This differential selectivity may result in clinical benefit by altering the safety profile. In the phase 1 portion of this phase 1/2 study, pts in chronic phase with imatinib relapsed or refractory disease were eligible for treatment with SKI-606 once-daily dosing. 18 pts [median age: 62 yrs (range 27 – 72); 14 male; 4 female; median CML duration: 5.8 yrs (range 0.9 – 11.1); and median time on imatinib (n=16): 3.9 yrs (range 0.8 – 6.5)] have been enrolled in the following dose cohorts (mg/day): 400 (3 pts), 500 (3 pts) and 600 (12 pts), and have been on treatment for 30 to 192 days. 17/18 pts remain on study; 1 pt discontinued with disease progression. The following SKI-606-related AEs have been reported (n=15, G1/2): diarrhea (87%), nausea (33%), vomiting (20%), abdominal pain (13%), rash (13%), asthenia (13%), and increased AST/ALT levels (7%). 2 pts treated at 600 mg experienced a G3 toxicity: rash and thrombocytopenia. 5 pts (4 pts at 600 mg and 1 pt at 500 mg) had dose reductions for rash, thrombocytopenia, diarrhea, fever and increased AST/ALT levels. No pleural effusion or pulmonary edema has been reported. Of the 7 pts who entered the study in hematologic relapse and have completed 1 month of treatment, all have achieved complete hematologic response. Of the 7 pts on treatment ≥ 12 weeks (time of first cytogenetic assessment), 3 pts have achieved complete cytogenetic response and 1 pt a minimal cytogenetic response. 6/7 pts who have achieved complete hematologic response had pre-treatment imatinib-resistant Bcr-Abl mutations: M351T; F359V; T315I; F359(V,F); and 2 pts with multiple mutations [L248(L,V) and H396(H,R); H396(H,P) and E286(E,G) and M351(T,M)]. The 3 pts with complete cytogenetic response had mutations: M351T; M244V; and H396(H,P), E286(E,G) and M351(T,M). Based on the emergence of 1 DLT of G3 rash, and additional G2 GI and dermatologic toxicities observed at 600 mg, 500 mg has been selected as the dose for the phase 2 portion of the study. Patients in all phases of CML and Ph+ ALL are now being enrolled. SKI-606 is well tolerated in pts with CML, with a primarily GI and dermatologic safety profile, and with encouraging evidence of clinical activity in imatinib-resistant patients with complete hematologic and cytogenetic responses.
Solid-State and High-Resolution Liquid <sup>119</sup>Sn NMR Spectroscopy of Some Monomeric, Two-Coordinate Low-Valent Tin Compounds:  Very Large Chemical Shift Anisotropies (2000)

High-resolution liquid- and solid-state 119Sn NMR spectroscopy was used to study the bonding environment in the series of monomeric, two-coordinate Sn(II) compounds of formula Sn(X)C6H3-2,6-Trip2 (X = Cl, Cr(eta 5-C5H5)(CO)3, t-Bu, Sn(Me)2C6H3-2,6-Trip2; Trip = C6H2-2,4,6-i-Pr3). The trends in the principal components of the chemical shift tensor extracted from the solid-state NMR data were consistent with the structures determined by X-ray crystallography. Furthermore, the spectra for the first three compounds displayed the largest 119Sn NMR chemical shift anisotropies (up to 3798 ppm) of any tin compound for which data are currently available. Relaxation time based calculations for the dimetallic compound 2,6-Trip2H3C6Sn-Sn(Me)2C6H3-2,6-Trip2 suggests that the chemical shift anisotropy for the two-coordinate tin center may be as much as ca. 7098 ppm, which is as broad as the 1 MHz bandwidth of the NMR spectrometer.
Marker-free automatic quantification of red blood cell fluctuations with different storage periods by holographic imaging (2019)

This paper overviews the methods to quantitatively measure the cell membrane fluctuation (CMF) rate of red blood cells (RBCs) with different storage periods with millisecond temporal sensitivity at the single-cell level by using marker-free holographic imaging techniques. We quantitatively measured fluctuations in the discocyte shape of RBCs membrane, ring and dimple in the case of storage lesion with time-lapse phase images of RBCs. Our experimental results demonstrate that normal RBCs with a discocyte shape become stiffer with storage period and there is a significant negative correlation between CMFs and the sphericity coefficient, which describes the RBCs morphology. Correlation between CMF and projected surface area is also performed.
GLIADIN MODIFICATIONS CATALYZED BY GUINEA PIG LIVER TRANSGLUTAMINASE (1993)

Wheat gliadins, that are glutamine rich and lysine poor proteins, are good substrates for transglutaminases reactions. This study was conducted to determine the efficiency with which guinea pig liver transglutaminase catalyzes transfer and hydrolysis reactions of native and acylated gliadins. In all reactions, 35% of the total glutaminyl residues were modified. Neutral pH simultaneously enhanced glutaminyl residue hydrolysis and protein cross-linking, while acidic pH reduced the cross-linking reaction. Functional properties of two enzymatically modified gliadins and a chemically deamidated one were tested at neutral pH. A deamidation level of 25–27% appeared to be an optimum for the emulsification properties. Enzymatically modified gliadin showed better resistance to coalescence than the chemically deamidated one; a result that probably is related to the presence of high molecular weight polymers.
An Active-Under-Coil RFDAC With Analog Linear Interpolation in 28-nm CMOS (2021)

This paper demonstrates a wideband 2.4 GHz <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$2\times 9$ </tex-math></inline-formula> -bit Cartesian radio-frequency digital-to-analog converter (RFDAC). Active-under-coil integration is introduced in the physical implementation, where all key active circuitry is located underneath the matching-network transformer, achieving a core area of merely 0.35 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . An <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$8\times $ </tex-math></inline-formula> analog linear interpolation at the RF rate is proposed to suppress replicas close to the carrier while avoiding any high-order and high-speed digital filters in digital processing back-end. The multi-port transformer is adopted in the matching network to improve the back-off efficiency. The measured peak output power and drain efficiency at the center frequency of 2.4 GHz are 17.47 dBm and 17.6% respectively, while the peak efficiency is 19.03%. Moreover, the 6-dB back-off efficiency is at 66% of that at the peak output power. The active-under-coil integration helps this RFDAC to achieve the smallest area among comparable prior arts.
Antifungal and Antibiofilm Activity of Cyclic Temporin L Peptide Analogues against Albicans and Non-Albicans Candida Species (2022)

Temporins are one of the largest families of antimicrobial peptides with both anti-inflammatory and antimicrobial activity. Herein, for a panel of cyclic temporin L isoform analogues, the antifungal and antibiofilm activities were determined against representative <i>Candida</i> strains, including <i>C. albicans</i>, <i>C. glabrata</i>, <i>C. auris</i>, <i>C. parapsilosis</i> and <i>C. tropicalis</i>. The outcomes indicated a significant anti-candida activity against planktonic and biofilm growth for four peptides (<b>3</b>, <b>7</b>, <b>15</b> and <b>16</b>). The absence of toxicity up to high concentrations and survival after infection were assessed in vivo by using <i>Galleria mellonella</i> larvae, and the correlation between conformation and cytotoxicity was investigated by fluorescence assays and circular dichroism (CD). By combining fluorescence spectroscopy, CD, dynamic light scattering, confocal and atomic force microscopy, the mode of action of four analogues was hypothesized. The results pinpointed that peptide <b>3</b> emerged as a non-toxic compound showing a potent antibiofilm activity and represents a promising compound for biomedical applications.
Can baseline serum microRNAs predict response to TNF-alpha inhibitors in rheumatoid arthritis? (2016)

To date, no miRNA consistently predicting response to TNFi therapy in RA has been identified. Future studies on this topic should meet a minimum of standards in design that are addressed in this study, in order to increase the reproducibility.
Supplementary Table S2 from Early Infiltration of Innate Immune Cells to the Liver Depletes HNF4α and Promotes Extrahepatic Carcinogenesis (2023)

&lt;p&gt;Supplementary Table S2 lists the antibodies used for western blots&lt;/p&gt;
262. Therapeutic Suppression of the KRAS-MYC Oncogenic Axis in Human Pancreatic Cancer Xenografts with U1 Adaptor Oligonucleotide / RGD Peptide Conjugates (2016)

U1 Adaptors are synthetic oligonucleotides that enable the U1 small nuclear ribonucleoprotein (U1 snRNP) complex to stably bind within the terminal exon of a specific pre-mRNA. This interferes with the obligatory polyadenylation step in mRNA maturation, causing selective destruction of the targeted mRNA inside the nucleus. In contrast to siRNA or antisense oligos, U1 Adaptors can accept extensive covalent modifications for nuclease resistance, targeted delivery or in-vivo imaging without loss of silencing activity, offering important advantages as therapeutic agents. A panel of candidate U1 Adaptors targeting human KRAS (KRAS Adaptors) was screened in vitro using the human pancreatic cancer cell line MIA-PaCa2. The best candidates reduced KRAS mRNA expression by up to 76% - as effectively as siRNA controls. Reduced KRAS protein expression was confirmed by western blot. Inhibition of cell growth in vitro and increased apoptosis were seen for both the MIA-PaCa2 (KRASG12C) and Panc1(KRASG12D) cell lines, but not in BxPC3, a KRASwildtype pancreatic cancer cell line. In a parallel project, U1 Adaptors targeting human MYC mRNA were designed and screened in B-cell lymphoma lines, where the best candidates reduced MYC mRNA levels by over 95%. Because of the observed relationship between activating KRAS mutation and MYC overexpression in pancreatic cancers, MYC Adaptors were tested in MIA-PaCa2 cells. MYC Adaptors also inhibited cell growth and increased apoptosis in vitro. U1 Adaptors were tested for efficacy in mice bearing subcutaneous MIA-PaCa2 xenograft tumors. For in-vivo delivery, Adaptor oligos were directly conjugated to a cyclic RGD-motif peptide (cRGD), which is a targeting ligand for specific integrin-family receptors overexpressed on parenchyma and endothelial cells of many solid tumors. Alternately, U1 Adaptor oligos were linked to “internalizing” RGD (iRGD), a variant RGD peptide that also triggers permeabilization of tumor endothelium and internalization by cells through secondary binding to neuropilin-1. KRAS Adaptors linked to cRGD or iRGD were administered by tail vein injections twice weekly for three to four weeks. Over a series of experiments, tumor growth was inhibited by averages of 68% to 93%. Tumor stasis or regression occurred in some treated mice. In a pilot study, MYC Adaptors conjugated to iRGD peptide were also highly effective in suppressing tumor growth and inducing tumor regression. Excised tumors were analyzed by qPCR and western blot, which confirmed reductions of the targeted mRNAs and proteins. We have shown that U1 Adaptors conjugated to tumor-targeting / tumor-penetrating peptides can effectively target human KRAS and MYC oncogenes in vivo. These results support the continued development of U1 Adaptor technology as a strategy for therapeutic suppression of KRAS, MYC and possibly other oncogene targets in pancreatic cancer.
Clinical profile of patients with ATP1A3 mutations in Alternating Hemiplegia of Childhood—a study of 155 patients (2015)

Our results, demonstrate a highly variable clinical phenotype in patients with AHC2 that correlates with certain mutations and possibly clusters within the ATP1A3 gene. Our description of the clinical profile of patients with the most frequent mutations and the clinical picture of those with less common mutations confirms the results from previous studies, and further expands the spectrum of genotype-phenotype correlations. Our results may be useful to confirm diagnosis and may influence decisions to ensure appropriate early medical intervention in patients with AHC. They provide a stronger basis for the constitution of more homogeneous groups to be included in clinical trials.
Upgrading Pretransplant Human Islet Culture Technology Requires Human Serum Combined With Media Renewal (2010)

BACKGROUND.: The original Edmonton protocol used fresh islets, but for obvious logistic advantages most transplant centers have implemented pretransplant culture in human albumin. The aim of this study was to improve current pretransplant human islet culture techniques. METHODS.: Clinical-grade purified human islets from a total of 24 donors were directly resuspended after isolation in CMRL 1066-based media at 37 degrees C, and media additions and renewal were tested. At days 1 and 5 of culture, in vitro quality controls included islet viability, insulin content and function, apoptosis, and in vivo islet potency assay in nude mice. RESULTS.: Replacing human albumin with human AB serum improved 1- and 5-day preservation of islet function and viability which was further enhanced with antioxidant Stem Ease, leading to the iCulture medium (enriched CMRL: pyruvate, zinc sulfate, insulin, transferrin, selenium, 2.5% human AB serum and Stem Ease). Major damage occurs in the first day of culture and frequent media renewal (25% vol/hr) in this period further improved viability, apoptosis, islet recovery, and function in vitro and in vivo, compared with only changing medium after overnight culture. CONCLUSIONS.: The described human islet culture technique (iCulture medium+renewal) seems to be the best choice for clinical human islet culture when short (1 day) or long (5 days) periods are used. Media choice and dilution play a major role in the function and survival of human islets in culture.
Requirement for Transcription Factor <i>Ets1</i> in B Cell Tolerance to Self-Antigens (2015)

The differentiation and survival of autoreactive B cells is normally limited by a variety of self-tolerance mechanisms, including clonal deletion, anergy, and clonal ignorance. The transcription factor c-ets-1 (encoded by the Ets1 gene) has B cell-intrinsic roles in regulating formation of Ab-secreting cells by controlling the activity of Blimp1 and Pax5 and may be required for B cell tolerance to self-antigen. To test this, we crossed Ets1(-/-) mice to two different transgenic models of B cell self-reactivity, the anti-hen egg lysozyme BCR transgenic strain and the AM14 rheumatoid factor transgenic strain. BCR transgenic Ets1(-/-) mice were subsequently crossed to mice either carrying or lacking relevant autoantigens. We found that B cells lacking c-ets-1 are generally hyperresponsive in terms of Ab secretion and form large numbers of Ab-secreting cells even in the absence of cognate Ags. When in the presence of cognate Ag, different responses were noted depending on the physical characteristics of the Ag. We found that clonal deletion of highly autoreactive B cells in the bone marrow was intact in the absence of c-ets-1. However, peripheral B cells lacking c-ets-1 failed to become tolerant in response to stimuli that normally induce B cell anergy or B cell clonal ignorance. Interestingly, high-affinity soluble self-antigen did cause B cells to adopt many of the classical features of anergic B cells, although such cells still secreted Ab. Therefore, maintenance of appropriate c-ets-1 levels is essential to prevent loss of self-tolerance in the B cell compartment.
Decreased defluorination using the novel beta-cell imaging agent [18F]FE-DTBZ-d4 in pigs examined by PET (2011)

[18F]FE-DTBZ-d4 has similar PK and PD properties for VMAT2 imaging as its non-deuterated analogue [18F]FE-DTBZ in addition to gaining significantly increased stability against defluorination. [18F]FE-DTBZ-d4 is a prime candidate for future preclinical and clinical studies on focal clusters of beta cells, such as in intramuscular islet grafts.
The effect of microstructural inhomogeneity on thermal diffusivity in a rheocast component (2016)

Semi-Solid Metal (SSM) casting is a promising technology offering an opportunity to manufacture net-shape, complex geometry metal components in a single operation. However, the absence of foundry guidelines and limited design data for SSM casting makes it challenging to predict the performance of both process and components. The objective of this research was to develop and offer new solutions to material processing-related issues in the electronics industry. By investigating the opportunities afforded by the recently developed RheoMetalTM rheocasting process, a better understanding of the critical factors needed for an effective manufacturing process and optimised component characteristics was achieved.A study of the evolution of microstructure at different stages of the RheoMetalTM process demonstrated the influence of multistage solidification on the microstructural characteristics of the rheocast components. The microstructure of a slurry consists of the solute-lean and coarse globular α-Al particles with a uniform distribution of alloying elements, suspended in the liquid matrix. Additional solute-rich α-Al particles were identified as being a consequence of discrete nucleation events taking place after the initial slurry production. In the final components, macrosegregation was observed in the form of variations in the ratio of solute-lean coarse globular α-Al particles and solute-rich fine α-Al particles in both longitudinal and transverse directions.The relation between microstructural characteristics and material properties was established by determination of the local properties of a rheocast component. The fracture of a rheocast telecom component was strongly affected by microstructural inhomogeneity. In particular, macrosegregation in the form of liquid surface segregation bands and sub-surface pore bands strongly affected the fracture behaviour. Thermal conductivity measurements revealed that regions of the component with a high amount of solute-lean globular α-Al particles showed higher thermal conductivity. The effect of the local variation in thermal conductivity on the thermal performance of a large rheocast heatsink was evaluated by simulation. The results clearly show the importance of considering material inhomogeneity when creating a robust component design.
Supplementary Material SM2 from Comprehensive Genome Profiling in Patients With Metastatic Non–Small Cell Lung Cancer: The Precision Medicine Phase II Randomized SAFIR02-Lung/IFCT 1301 Trial (2023)

&lt;p&gt;Supplementary materials - substudy 2 statistical report&lt;/p&gt;
Electrical-stress-induced degradation in AlGaN/GaN high electron mobility transistors grown under gallium-rich, nitrogen-rich, and ammonia-rich conditions (2010)

We have evaluated the long-term electrical reliability of GaN/AlGaN high-electron-mobility transistors grown under Ga-rich, N-rich, and NH3-rich conditions. Vpinch-off shifts positively after stress for devices grown under Ga-rich and N-rich conditions, while it shifts negatively for NH3-rich devices. Density functional theory calculations suggest that the hot-electron-induced release of hydrogen from hydrogenated Ga-vacancies is primarily responsible for the degradation of devices grown in Ga-rich and N-rich conditions, while hydrogenated N-antisites are the dominant defects causing degradation in devices grown under NH3-rich conditions.
Signatures of Recombination in Clonal Lineages of the Citrus Brown Spot Pathogen, <i>Alternaria alternata</i> sensu lato (2013)

Most Alternaria spp. are considered asexual but recent molecular evolution analyses of Alternaria mating-type genes show that the mating locus is under strong purifying selection, indicating a possible role in sexual reproduction. The objective of this study was to determine the mode of reproduction of an Alternaria alternata sensu lato population causing citrus brown spot in central Florida. Mating type of each isolate was determined, and isolates were sequenced at six putatively unlinked loci. Three genetically distinct subpopulations (SH1, SH4A, and SH4B) were identified using network and Bayesian population structure analyses. Results demonstrate that most subpopulations of A. alternata associated with citrus are clonal but some have the ability to extensively recombine through a cryptic sexual cycle or parasexual cycle. Although isolates were sampled in close physical proximity (≈2,500-m² area), we were able to reject a random mating model using multilocus gametic disequilibrium tests for two subpopulations, SH1 and SH4B, suggesting that these subpopulations were predominantly asexual. However, three recombination events were identified in SH1 and SH4B and localized to individuals of opposite mating type, possibly indicating meiotic recombination. In contrast, in the third subpopulation (SH4A), where only one mating type was present, extensive reticulation was evident in network analyses, and multilocus gametic disequilibrium tests were consistent with recombination. Recombination among isolates of the same mating type suggests that a nonmeiotic mechanism of recombination such as the parasexual cycle may be operating in this subpopulation. The level of gene flow detected among subpopulations does not appear to be sufficient to prevent differentiation, and perhaps future speciation, of these A. alternata subpopulations.