gebhart/patrepeval huggingface dataset:
Influence of Human Serum Albumin Content in Formulations on the Bioequivalency of Interferon Alfa‐2a Given by Subcutaneous Injection in Healthy Male Volunteers (1995)

To determine the influence of human serum albumin (HSA) content in formulations on the bioequivalency of recombinant interferon alfa-2a, a double-blind, randomized, two-way crossover study was conducted in 24 healthy male volunteers. Subjects received a single subcutaneous injection of 18 million IU of Roferon-A reconstituted with either the diluent containing 10 mg of HSA or the HSA-free diluent; final HSA contents in the 2 formulations were 15 mg and 5 mg, respectively. Administration of the 2 formulations resulted in similar 48-hour Roferon-A serum concentration-time profiles and comparable frequency and intensity of adverse events. The statistical analysis using the two one-sided tests procedure showed that both formulations were bioequivalent for pharmacokinetic parameters such as Cmax, tmax, AUC48, and AUC. We conclude that a threefold change in HSA content in formulations does not alter the bioequivalency of Roferon-A.
Partitioning of cancer therapeutics in nuclear condensates (2020)

The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates concentrate small-molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this occurs through physicochemical properties independent of the drug target. This behavior was also observed in tumor cells, where drug partitioning influenced drug activity. Altering the properties of the condensate was found to affect the concentration and activity of drugs. These results suggest that selective partitioning and concentration of small molecules within condensates contributes to drug pharmacodynamics and that further understanding of this phenomenon may facilitate advances in disease therapy.
Design and synthesis of germline-based hemi-humanized single-chain Fv against the CD18 surface antigen (2000)

The 6.7 murine monoclonal antibody (mAb) recognizes the human CD18 antigen and is therefore of interest as an anti-inflammatory agent. The 6.7 heavy variable chain (VH) was humanized using the closest human germline sequence as the template on to which to graft the murine complementary determining regions (CDRs). Two versions were proposed, one in which the residue proline 45 of the murine form was maintained and another in which this framework residue was changed to the leucine found in the human sequence. These VH humanized versions were expressed in the yeast Pichia pastoris as hemi-humanized single-chain Fv (scFvs), with the VL from the murine antibody. The scFv from the murine antibody was also expressed. The binding activities of the murine and both hemi-humanized scFvs were determined by flow cytometry analysis. All the constructions were able to recognize human lymphocytes harboring CD18, indicating successful humanization with transfer of the original binding capability. Some differences between the two hemi-humanized versions were observed. The method used was simple and straightforward, with no need for refined structural analyses and could be used for the humanization of other antibodies.
Reaktionen mit Silylaziden, 7. Über 4‐Isocyanatocarbonsäure‐trimethylsilylester und 4‐Aminocarbonsäure‐N‐carbonsäureanhydride (1975)

Abstract Durch Umsetzung cyclischer 1,3‐Dicarbonsäureanhydride ( 10, 11, 12, 15 ) mit Trimethylsilylazid ( 9 ) wurden verschiedene 4‐Isocyanatocarbonsäure‐trimethylsilylester ( 6a–h, 13, 14, 16, 17 ) erhalten. Durch schonende Hydrolyse dieser Silylester ließen sich die entsprechenden 4‐Isocyanatocarbonsäuren freisetzen, die in allen Fällen der Additionspolymerisation zu den unbeständigen, linearen Oligo(4‐Aminocarbonsäure‐ N ‐carbonsäureanhydriden) unterliegen. Parallel dazu erfolgt in manchen Fällen Cyclisierung zu kristallinen, siebengliedrigen 4‐Aminocarbonsäure‐NCA ( 20—25 ), die aber nicht von allen 4‐Isocyanatocarbonsäuren beobachtet oder isoliert werden konnten. Beim Erhitzen sowie unter basischer Katalyse decarboxylieren sowohl die linearen als auch die cyclischen NCA unter Bildung von Oligoamiden ( 36, 37 ); parallel dazu erfolgt auch Ringverengung zu den entsprechenden fünfgliedrigen Lactamen ( 26–30 ), die insbesondere bei der thermischen Decarboxylierung die Hauptprodukte sind. Hochmolekulare Polyamide wurden in keinem Fall erhalten.
The ras Superfamily of GTPases (1993) (2017)

The ras oncogenes are highly conserved in evolution. Homologs of these genes have been found in many eukaryotes, including unicellular 18, 23, 32, 75, 78 and complex multicellular organisms. 26, 40 70 It is likely that ras homologs will be found in all eukaryotic organisms. Certainly there are no other oncogenes presently known that are as highly conserved. The degree of identify between the mammalian oncogenic RAS proteins and the RAS proteins of the yeasts Saccharomyces cerevisiae (RASI and RAS2) and Schizosaccharomyces pombe (ras1) in the N terminal halves of the molecules is about 90%. To put this into perspective, the degree of identity between the cAMP-dependent protein kinase regulatory subunits from yeasts and mammals is in the range of 50%. 95 These subunits bind two molecules of cAMP apiece, dimerize, bind the catalytic sub-unit, release the catalytic subunit from inhibition upon binding cAMP, and retain the ability to interact with the catalytic subunit of the divergent organisms. 42, 111 From this example it is reasonable to infer that the level of conservation of primary structure observed for RAS is associated with the conservation of many biochemical functions. This inference is correct.
Capacitor-Current-Feedback Active Damping With Reduced Computation Delay for Improving Robustness of LCL-Type Grid-Connected Inverter (2013)

This paper investigates the capacitor-current-feedback active damping for the digitally controlled LCL-type grid-connected inverter. It turns out that proportional feedback of the capacitor current is equivalent to virtual impedance connected in parallel with the filter capacitor due to the computation and pulse width modulation (PWM) delays. The LCL-filter resonance frequency is changed by this virtual impedance. If the actual resonance frequency is higher than one-sixth of the sampling frequency (f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">s</sub> /6), where the virtual impedance contains a negative resistor component, a pair of open-loop unstable poles will be generated. As a result, the LCL-type grid-connected inverter becomes much easier to be unstable if the resonance frequency is moved closer to f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">s</sub> /6 due to the variation of grid impedance. To address this issue, this paper proposes a capacitor-current-feedback active damping with reduced computation delay, which is achieved by shifting the capacitor current sampling instant towards the PWM reference update instant. With this method, the virtual impedance exhibits more like a resistor in a wider frequency range, and the open-loop unstable poles are removed; thus, high robustness against the grid-impedance variation is acquired. Experimental results from a 6-kW prototype confirm the theoretical expectations.
CT Evaluation of the Response of Gastrointestinal Stromal Tumors After Imatinib Mesylate Treatment: A Quantitative Analysis Correlated with FDG PET Findings (2004)

FDG PET is sensitive and specific for evaluating tumor response but cannot be used in patients whose baseline FDG PET results are negative for tumors. Although subjective evaluation was a better indicator of treatment response than was tumor density alone, the tumor density measurement is a good indicator and provides a reliable quantitative means of monitoring the tumor. RECIST, using only tumor size, was unreliable for monitoring GISTs during the early stage of imatinib mesylate treatment.
Immunogenicity and Safety of Yellow Fever Vaccine (Stamaril) When Administered Concomitantly With a Tetravalent Dengue Vaccine Candidate in Healthy Toddlers at 12–13 Months of Age in Colombia and Peru (2016)

Concomitant administration of YF vaccine with CYD-TDV has no relevant impact on the immunogenicity or safety profile of the YF vaccine.
IL-12 enhances the natural killer cell cytokine response to Ab-coated tumor cells (2002)

The anti-tumor activity of recombinant mAb's directed against tumor cell growth receptors has generally been considered to result from direct antiproliferative effects, the induction of apoptosis, or possibly Ab-dependent cellular cytotoxicity mediated against tumor targets. However, it remains unclear to what degree these mechanisms actually aid in the clearance of Ab-coated tumor cells in vivo. We show here that NK cells secrete a distinct profile of potent immunostimulatory cytokines in response to dual stimulation with Ab-coated tumor cells and IL-12. This response could not be duplicated by costimulation with other ILs and was significantly enhanced in the presence of monocytes. Cytokine production was dependent upon synergistic signals mediated by the activating receptor for the Fc portion of IgG (FcgammaRIII) and the IL-12 receptor expressed on NK cells. Coadministration of Ab-coated tumor cells and IL-12 to BALB/c mice resulted in enhanced circulating levels of NK cell-derived cytokines with the capacity to augment anti-tumor immunity. These findings suggest that, in addition to mediating cellular cytotoxicity and apoptosis, the anti-tumor activity of mAb's might also result from activation of a potent cytokine secretion program within immune effectors capable of recognizing mAb-coated targets.
Gene Targeting to the Centromeric DNA of a Human Minichromosome (1996)

A human supernumerary minichromosome (MC), previously identified as a derivative of chromosome 9, has been introduced into Chinese hamster ovary (CHO) cells by means of cell fusion. A hybrid clone containing the MC as the only free human chromosome was isolated. A selectable marker gene (neo) inserted into a yeast artificial chromosome (YAC) has been successfully targeted to the MC centromeric DNA via co-transfection with chromosome-9-specific alpha satellite DNA. In situ hybridization and Southern blotting experiments demonstrated that the intact neo gene was integrated into the MC centromeric DNA. Studies on the clonal distribution and on the stability of the MC either in the presence or in the absence of the selective agent have been carried out. The MC is susceptible to further manipulations and may thus represent a model for the construction of a large-capacity vector for somatic gene therapy.
Influence of Methotrexate and Azathioprine on Radiologic Progression in Rheumatoid Arthritis (1991)

Patients with rheumatoid arthritis treated with low-dose methotrexate showed significantly less radiologic progression than patients treated with azathioprine. This result suggests that methotrexate therapy is clinically superior in these patients.
Super-Resolution Fingerprinting Detects Chemical Reactions and Idiosyncrasies of Single DNA Pegboards (2013)

We employ the single-particle fluorescence nanoscopy technique points accumulation for imaging in nanoscale topography (PAINT) using site-specific DNA probes to acquire two-dimensional density maps of specific features patterned on nanoscale DNA origami pegboards. We show that PAINT has a localization accuracy of ~10 nm that is sufficient to reliably distinguish dense (>10(4) features μm(-2)) sub-100 nm patterns of oligonucleotide features. We employ two-color PAINT to follow enzyme-catalyzed modification of features on individual origami and to show that single nanopegboards exhibit stable, spatially heterogeneous probe-binding patterns, or "fingerprints." Finally, we present experimental and modeling evidence suggesting that these fingerprints may arise from feature spacing variations that locally modulate the probe binding kinetics. Our study highlights the power of fluorescence nanoscopy to perform quality control on individual soft nanodevices that interact with and position reagents in solution.
Using Situs for the integration of multi-resolution structures (2010)

Situs is a modular and widely used software package for the integration of biophysical data across the spatial resolution scales. It has been developed over the last decade with a focus on bridging the resolution gap between atomic structures, coarse-grained models, and volumetric data from low-resolution biophysical origins, such as electron microscopy, tomography, or small-angle scattering. Structural models can be created and refined with various flexible and rigid body docking strategies. The software consists of multiple, stand-alone programs for the format conversion, analysis, visualization, manipulation, and assembly of 3D data sets. The programs have been ported to numerous platforms in both serial and shared memory parallel architectures and can be combined in various ways for specific modeling applications. The modular design facilitates the updating of individual programs and the development of novel application workflows. This review provides an overview of the Situs package as it exists today with an emphasis on functionality and workflows supported by version 2.5. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12551-009-0026-3) contains supplementary material, which is available to authorized users.
Sequential Elimination of Major-Effect Contributors Identifies Additional Quantitative Trait Loci Conditioning High-Temperature Growth in Yeast (2008)

Several quantitative trait loci (QTL) mapping strategies can successfully identify major-effect loci, but often have poor success detecting loci with minor effects, potentially due to the confounding effects of major loci, epistasis, and limited sample sizes. To overcome such difficulties, we used a targeted backcross mapping strategy that genetically eliminated the effect of a previously identified major QTL underlying high-temperature growth (Htg) in yeast. This strategy facilitated the mapping of three novel QTL contributing to Htg of a clinically derived yeast strain. One QTL, which is linked to the previously identified major-effect QTL, was dissected, and NCS2 was identified as the causative gene. The interaction of the NCS2 QTL with the first major-effect QTL was background dependent, revealing a complex QTL architecture spanning these two linked loci. Such complex architecture suggests that more genes than can be predicted are likely to contribute to quantitative traits. The targeted backcrossing approach overcomes the difficulties posed by sample size, genetic linkage, and epistatic effects and facilitates identification of additional alleles with smaller contributions to complex traits.
Comparison of formats for the development of fiber-optic biosensors utilizing sol–gel derived materials entrapping fluorescently-labelled protein (1999)

The development of fiber-optic biosensors requires that a biorecognition element and a fluorescent reporter group be immobilized at or near the surface of an optical element such as a planar waveguide or optical fiber. In this study, we examined a model biorecognition element–reporter group couple consisting of human serum albumin that was site-selectively labelled at Cys 34 with iodoacetoxy-nitrobenzoxadiazole (HSA–NBD). The labelled protein was encapsulated into sol–gel derived materials that were prepared either as monoliths, as beads that were formed at the distal tip of a fused silica optical fiber, or as thin films that were dipcast along the length of a glass slide or optical fiber. For fiber-based studies, the entrapped protein was excited using a helium–cadmium laser that was launched into a single optical fiber, and emission was separated from the incident radiation using a perforated mirror beam-splitter, and detected using a monochromator–photomultiplier tube assembly. Changes in fluorescence intensity were generated by denaturant-induced conformational changes in the protein or by iodide quenching. The analytical parameters of merit for the different encapsulation formats, including minimum protein loading level, response time and limit-of-detection, were examined, as were factors such as protein accessibility, leaching and photobleaching. Overall, the results indicated that both beads and films were suitable for biosensor development. In both formats, a substantial fraction of the entrapped protein remained accessible, and the entrapped protein retained a large degree of conformational flexibility. Thin films showed the most rapid response times, and provided good detection limits for a model analyte. However, the entrapment of proteins into beads at the distal tip of fibers provided better signal-to-noise and signal-to-background ratios, and required less protein for preparation. Hence, beads appear to be the most viable method for interfacing of proteins to optical fibers.
Genetic analysis of potassium transport loci in Escherichia coli: evidence for three constitutive systems mediating uptake potassium (1991)

The analysis of mutants of Escherichia coli that require elevated concentrations of K+ for growth has revealed two new genes, trkG, near minute 30 within the cryptic rac prophage, and trkH, near minute 87, the products of which affect constitutive K+ transport. The analysis of these and other trk mutations suggests that high rates of transport, previously considered to represent the activity of a single system, named TrkA, appear to be the sum of two systems, here named TrkG and TrkH. Each of these two is absolutely dependent on the product of the trkA gene, a cytoplasmic protein associated with the inner membrane (D. Bossemeyer, A. Borchard, D. C. Dosch, G. C. Helmer, W. Epstein, I. R. Booth, and E. P. Bakker, J. Biol. Chem. 264:16403-16410, 1989). The TrkH system is also dependent on the products of the trkH and trkE genes, while the TrkG system is also dependent on the product of the trkG gene and partially dependent on the product of the trkE gene. It is suggested that the trkH and trkG products are membrane proteins that form the transmembrane path for the K+ movement of the respective systems. Two mutations altering the trkA product reduce the affinity for K+ of both TrkG and TrkH, indicating that changes in peripheral protein can alter the conformation of the sites at which K+ is bound prior to transport. The TrkD system has a relatively modest rate of transport, is dependent solely on the product of the trkD gene, and is the sole saturable system for Cs+ uptake in this species (D. Bossemeyer, A. Schlösser, and E. P. Bakker, J. Bacteriol. 171:2219-2221, 1989).
Clinical development of recombinant human interleukin-11 to treat chemotherapy-induced thrombocytopenia (1996)

Recombinant human interleukin-11 stimulates megakaryocytopoiesis in vitro and platelet production in vivo. A clinical program to investigate the use of recombinant human interleukin-11 in patients with chemotherapy-induced thrombocytopenia began in 1992. These studies show the potential of recombinant human interleukin-11 as a treatment for chemotherapy-induced thrombocytopenia. The other activities of recombinant human interleukin-11, such as its ability to ameliorate mucositis in myelosuppressed animal models, may contribute to its clinical benefits in patients receiving chemotherapy.
Decision Analysis: A Personal Account of How It Got Started and Evolved (2002)

Decision analysis: theory and practice, risk, sequential. Games and group decisions: negotiations. Professional: comments on
Quantum Correlations with Spacelike Separated Beam Splitters in Motion: Experimental Test of Multisimultaneity (2002)

Multisimultaneity is a causal model of relativistic quantum physics which assigns a real time ordering to any set of events, much in the spirit of the pilot-wave picture. Contrary to standard quantum mechanics, it predicts a disappearance of the correlations in a Bell-type experiment when both analyzers are in relative motion such that each one, in its own inertial reference frame, is first to select the output of the photons. We tested this prediction using acousto-optic modulators as moving beam splitters and interferometers separated by 55 m. We did not observe any disappearance of the correlations, in agreement with quantum mechanics.
Camera calibration methodology based on a linear perspective transformation error model (2003)

The camera model which uses homogeneous coordinates, assumes the laws of Gaussian optics, and an extension for the aberration of geometric radial distortion is included. Features that collectively demonstrate the methodology's superiority over existing techniques are: (1) the simultaneous and accurate inference of all camera model parameters using only iterative linear least squares; (2) no requirement of a priori knowledge of camera model parameters; (3) utilization with a wide range of optical sensing devices; (4) adaptability to include camera model parameters that are departures from the assumptions of Gaussian optics; and (5) computational efficiency. Absolute stereo calibration accuracy of 0.084 mm in a 2000 cm/sup 3/ volume is achieved for a pair of miniaturized CCD array cameras.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Detecting Mycoplasma bovis in milk by enzyme-linked immunosorbent assay, using monoclonal antibodies (1986)

Enzyme-linked immunosorbent assay, using monoclonal antibodies, was used to detect Mycoplasma bovis in milk samples from a dairy experiencing an epizootic of mastitis. This method was specific (100%) for M bovis. Broth enrichment increased the sensitivity from 65% to 86%, compared with standard culture methods.
Studies on Radiation-Induced Mammary Gland Neoplasia in the Rat: I. The Role of the Ovary in the Neoplastic Response of the Breast Tissue to Total- or Partial-Body X-Irradiation (1960)

E. P. Cronkite, C. J. Shellabarger, V. P. Bond, S. W. Lippincott, Studies on Radiation-Induced Mammary Gland Neoplasia in the Rat: I. The Role of the Ovary in the Neoplastic Response of the Breast Tissue to Total- or Partial-Body X-Irradiation, Radiation Research, Vol. 12, No. 1 (Jan., 1960), pp. 81-93
Refined characterization of head and neck squamous cell carcinomas expressing a seemingly wild‐type p53 protein (2005)

A large proportion of HNSCC with presumed wild-type p53 overexpression are false-negative cases. These results strengthen the established strong association of p53 protein overexpression with missense mutations. AI at TP53 and p16 loss are useful surrogate markers for genetic alterations of TP53 in HNSCC.