gebhart/patrepeval huggingface dataset:
A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2Rβγ-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors (2019)

NKTR-214 (bempegaldesleukin) is a novel IL2 pathway agonist, designed to provide sustained signaling through heterodimeric IL2 receptor βγ to drive increased proliferation and activation of CD8<sup>+</sup> T and natural killer cells without unwanted expansion of T regulatory cells (Treg) in the tumor microenvironment. In this first-in-human multicenter phase I study, NKTR-214 administered as an outpatient regimen was well tolerated and showed clinical activity including tumor shrinkage and durable disease stabilization in heavily pretreated patients. Immune activation and increased numbers of immune cells were observed in the periphery across all doses and cycles with no loss of NKTR-214 activity with repeated administration. On-treatment tumor biopsies demonstrated that NKTR-214 promoted immune cell increase with limited increase of Tregs. Transcriptional analysis of tumor biopsies showed that NKTR-214 engaged the IL2 receptor pathway and significantly increased genes associated with an effector phenotype. Based on safety and pharmacodynamic markers, the recommended phase II dose was determined to be 0.006 mg/kg every three weeks. SIGNIFICANCE: We believe that IL2- and IL2 pathway-targeted agents such as NKTR-214 are key components to an optimal immunotherapy treatment algorithm. Based on its biological activity and tolerability, NKTR-214 is being studied with approved immuno-oncology agents including checkpoint inhibitors.<i>See related commentary by Sullivan, p. 694</i>.<i>This article is highlighted in the In This Issue feature, p. 681</i>.
Silicon Carbide: Synthesis and Properties (2011)

Silicon carbide is an important non-oxide ceramic which has diverse industrial applications. In fact, it has exclusive properties such as high hardness and strength, chemical and thermal stability, high melting point, oxidation resistance, high erosion resistance, etc. All of these qualities make SiC a perfect candidate for high power, high temperature electronic devices as well as abrasion and cutting applications. Quite a lot of works were reported on SiC synthesis since the manufacturing process initiated by Acheson in 1892. In this chapter, a brief summary is given for the different SiC crystal structures and the most common encountered polytypes will be cited. We focus then on the various fabrication routes of SiC starting from the traditional Acheson process which led to a large extent into commercialization of silicon carbide. This process is based on a conventional carbothermal reduction method for the synthesis of SiC powders. Nevertheless, this process involves numerous steps, has an excessive demand for energy and provides rather poor quality materials. Several alternative methods have been previously reported for the SiC production. An overview of the most common used methods for SiC elaboration such as physical vapour deposition (PVT), chemical vapour deposition (CVD), sol-gel, liquid phase sintering (LPS) or mechanical alloying (MA) will be detailed. The resulting mechanical, structural and electrical properties of the fabricated SiC will be discussed as a function of the synthesis methods.
Defective plasma membrane assembly in yeast secretory mutants (1984)

Yeast mutants that are conditionally blocked at distinctive steps in secretion and export of cell surface proteins have been used to monitor assembly of integral plasma membrane proteins. Mutants blocked in transport from the endoplasmic reticulum (sec18), from the Golgi body (sec7 and sec14), and in transport of secretory vesicles (sec1) show dramatically reduced assembly of galactose and arginine permease activities. Simultaneous induction of galactose permease and alpha-galactosidase (a secreted glycoprotein) in sec mutant cells at the nonpermissive temperature (37 degrees C) shows that both activities accumulate and can be exported coordinately when cells are returned to the permissive temperature (24 degrees C) in the presence or absence of cycloheximide. Plasma membrane fractions isolated from sec mutant cells radiolabeled at 37 degrees C have been analyzed by two-dimensional sodium dodecyl sulfate-gel electrophoresis. Although most of the major protein species seen in plasma membranes from wild-type cells are not efficiently localized in sec18 or sec7, several of these proteins appear in plasma membranes from sec1 cells. These results may be explained by contamination of plasma membrane fractions with precursor vesicles that accumulate in sec1 cells. Alternatively, some proteins may branch off during transport along the secretory pathway and be inserted into the plasma membrane by a different mechanism.
Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets (2007)

Peripheral T cell lymphoma, unspecified (PTCL/U), the most common form of PTCL, displays heterogeneous morphology and phenotype, poor response to treatment, and poor prognosis. We demonstrate that PTCL/U shows a gene expression profile clearly distinct from that of normal T cells. Comparison with the profiles of purified T cell subpopulations (CD4+, CD8+, resting [HLA-DR-], and activated [HLA-DR+]) reveals that PTCLs/U are most closely related to activated peripheral T lymphocytes, either CD4+ or CD8+. Interestingly, the global gene expression profile cannot be surrogated by routine CD4/CD8 immunohistochemistry. When compared with normal T cells, PTCLs/U display deregulation of functional programs often involved in tumorigenesis (e.g., apoptosis, proliferation, cell adhesion, and matrix remodeling). Products of deregulated genes can be detected in PTCLs/U by immunohistochemistry with an ectopic, paraphysiologic, or stromal location. PTCLs/U aberrantly express, among others, PDGFRalpha, a tyrosine-kinase receptor, whose deregulation is often related to a malignant phenotype. Notably, both phosphorylation of PDGFRalpha and sensitivity of cultured PTCL cells to imatinib (as well as to an inhibitor of histone deacetylase) were found. These results, which might be extended to other more rare PTCL categories, provide insight into tumor pathogenesis and clinical management of PTCL/U.
Consensus Statement for Standard of Care in Spinal Muscular Atrophy (2007)

Spinal muscular atrophy is a neurodegenerative disease that requires multidisciplinary medical care. Recent progress in the understanding of molecular pathogenesis of spinal muscular atrophy and advances in medical technology have not been matched by similar developments in the care for spinal muscular atrophy patients. Variations in medical practice coupled with differences in family resources and values have resulted in variable clinical outcomes that are likely to compromise valid measure of treatment effects during clinical trials. The International Standard of Care Committee for Spinal Muscular Atrophy was formed in 2005, with a goal of establishing practice guidelines for clinical care of these patients. The 12 core committee members worked with more than 60 spinal muscular atrophy experts in the field through conference calls, e-mail communications, a Delphi survey, and 2 in-person meetings to achieve consensus on 5 care areas: diagnostic/new interventions, pulmonary, gastrointestinal/nutrition, orthopedics/rehabilitation, and palliative care. Consensus was achieved on several topics related to common medical problems in spinal muscular atrophy, diagnostic strategies, recommendations for assessment and monitoring, and therapeutic interventions in each care area. A consensus statement was drafted to address the 5 care areas according to 3 functional levels of the patients: nonsitter, sitter, and walker. The committee also identified several medical practices lacking consensus and warranting further investigation. It is the authors' intention that this document be used as a guideline, not as a practice standard for their care. A practice standard for spinal muscular atrophy is urgently needed to help with the multidisciplinary care of these patients.
Role of Lipid Modifications in Targeting Proteins to Detergent-resistant Membrane Rafts (1999)

Sphingolipid and cholesterol-rich Triton X-100-insoluble membrane fragments (detergent-resistant membranes, DRMs) containing lipids in a state similar to the liquid-ordered phase can be isolated from mammalian cells, and probably exist as discrete domains or rafts in intact membranes. We postulated that proteins with a high affinity for such an ordered lipid environment might be targeted to rafts. Saturated acyl chains should prefer an extended conformation that would fit well in rafts. In contrast, prenyl groups, which are as hydrophobic as acyl chains but have a branched and bulky structure, should be excluded from rafts. Here, we showed that at least half of the proteins in Madin-Darby canine kidney cell DRMs (other than cytoskeletal contaminants) could be labeled with [3H]palmitate. Association of influenza hemagglutinin with DRMs required all three of its palmitoylated Cys residues. Prenylated proteins, detected by [3H]mevalonate labeling or by blotting for Rap1, Rab5, Gbeta, or Ras, were excluded from DRMs. Rab5 and H-Ras each contain more than one lipid group, showing that hydrophobicity alone does not target multiply lipid-modified proteins to DRMs. Partitioning of covalently linked saturated acyl chains into liquid-ordered phase domains is likely to be an important mechanism for targeting proteins to DRMs.
Estolides Synthesis Catalyzed by Immobilized Lipases (2011)

Estolides are vegetable-oil-based lubricants obtained from oleic acid or any source of hydroxy fatty acids. In this work, the estolides synthesis from oleic acid and methyl ricinoleate (biodiesel from castor oil), using immobilized commercial lipases (Novozym 435, Lipozyme RM-IM, and Lipozyme TL-IM) in a solvent-free medium was investigated. Acid value was used to monitor the reaction progress by determining the consumption of acid present in the medium. Novozym 435 showed the best performance. Water removal improved the conversion. Novozym 435 was more active at atmospheric pressure. Novozym 435 was reused four times with conversion reaching 15% after the fourth reaction at 80°C. Estolides produced under the reaction conditions used in this work presented good properties, such as, low temperature properties as pour point (-24°C), viscosity (23.9 cSt at 40°C and 5.2 cSt at 100°C), and viscosity index (153).
The Banert Cascade: A Synthetic Sequence to Polyfunctional NH‐1,2,3‐triazoles. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
A recombinant measles virus expressing biologically active human interleukin-12. (1999)

Suppression of cell-mediated immunity (CMI) is well-documented during and after measles. This immunosuppression is suggested to result from decreased production of interleukin-12 (IL-12), a key interleukin for CMI. In an attempt to clearly discern the role of IL-12 in measles-induced immunosuppression, a measles virus (MV) that expresses biologically active human IL-12 was generated. This was achieved by inserting the coding sequences of the two subunits (p35 and p40) of human IL-12 separated by an internal ribosome entry site in an additional transcription unit between the H and the L genes of MV. Although the IL-12-expressing MV grew slightly slower than the normal MV, it stably maintained the inserted sequences (3.2 kb) and uniformly expressed the foreign genes after 10 passages in cell culture. These findings suggest that MV is a well-suited vector for delivery of proteins of immunogenic and therapeutic importance.
Membrane topology and omeprazole labeling of the gastric hydrogen ion-potassium-adenosinetriphosphatase (1993)

The gastric H+,K(+)-ATPase is an alpha beta heterodimer with close homology to the Na+,K(+)-ATPase. Digestion of intact cytoplasmic-side-out vesicles at a trypsin to protein ratio of 1/4 removed most of the cytoplasmic protein, leaving membrane-spanning pairs in high yield. These were visualized on gels and poly(vinylidene difluoride) (PVDF) membranes by sodium dodecyl sulfate solubilization of the membrane-embedded segments and labeling of the cysteine residues with fluorescein maleimide prior to electrophoresis. The membrane-spanning residues of the alpha subunit were found between positions 104 and 162 (M1/M2), 291 and 358(M3/M4), 776 and 835 (M5/M6), and 853 and 946 (M7/M8). Although this method did not detect membrane retention of the hydrophobic sequences subsequent to position 946, it provided biochemical evidence for at least eight membrane segments in the catalytic subunit. Intact vesicles containing this enzyme transport acid in the presence of KCl, valinomycin, and MgATP. Omeprazole accumulates in these acidified vesicles and converts to a cationic sulfenamide. This forms disulfides with accessible cysteines. The reaction with this extracytoplasmic thiol reagent inhibits ATPase activity. Full inhibition was obtained with a stoichiometry of 2.2 mol of omeprazole bound/mg of protein. Only the alpha subunit was labeled. The cysteines reacting with omeprazole were defined by proteolytic cleavage of 3H- or 14C-omeprazole-labeled enzyme followed by peptide sequencing of fragments separated on tricine gradient gels and transferred to PVDF membranes. Tryptic digestion at a 1/40 trypsin to protein ratio in the presence of ligands that stabilize the E2P form of the enzyme produced two large fragments, one of 68 kDa stretching from Glu47 to probably Arg666 that contained minor labeling and the other of 333 kDa beginning at Ala671 and extending to probably Arg946 that contained greater than 85% of the label. Digestion of labeled vesicles at 1/75 or 1/4 trypsin to protein ratios gave radioactive patterns consistent with labeling at Cys813 and/or Cys822 and at Cys892 and/or Cys927 and/or Cys938. V8 protease digestion of the solubilized alpha subunit produced a fragment extending from Ser838 to possible Asp900 that was omeprazole-labeled, showing that Cys892 was labeled and Cys927 and Cys938 were not. Hence, omeprazole labels the H+,K(+)-ATPase at cysteines within the M5/M6 and M7/M8 regions of the alpha subunit, accounting for its inhibitory action in vivo and in vitro.
Using an IQ Data to RF Power Transmitter to Realize a Highly-Efficient Transmit Chain for Current and Next-Generation Mobile Handsets (2008)

Combining and re-organizing the functions of multiple traditional transmitters and power amplifiers into a single unified multi-mode non-linear system results in improved performance and high efficiency. This in turn decreases the transmit chain footprint and lowers the bill of materials for applications such as mobile voice, data terminals, and femtocells. With this approach, RF designers will no longer be forced to choose between performance and efficiency, or reliability and cost, freeing them to design more optimal wireless systems.
Expression and functional analysis ofCititf1, an ascidianNK-2class gene, suggest its role in endoderm development (1999)

In solitary ascidians the fate of endoderm is determined at a very early stage of development and depends on cytoplasmic factors whose nature has not been determined. We have isolated a member of the NK-2 gene family, Cititf1, from the ascidian Ciona intestinalis, showing high sequence homology to mammalian TITF1. The Cititf1 gene was expressed in all endodermal precursors at the pregastrula and gastrula stages, and is thus the first specific regulatory endodermal marker to be isolated from an ascidian. Cititf1 expression was downregulated at the end of gastrulation to reappear at middle tailbud and larval stages in the most anterior and ventral parts of head endoderm, regions which give rise, after metamorphosis, to the adult endostyle, where Cititf1 mRNA was still present. Microinjection of Cititf1 mRNA into fertilized eggs resulted in tadpole larvae with abnormalities in head-trunk development consequent to the formation of excess endoderm, perhaps due to recruitment of notochord precursors to an endodermal fate. These data suggest that Cititf1 plays an important role in normal endoderm differentiation during ascidian embryogenesis.
Sequence Mining and Pattern Analysis in Drilling Reports with Deep Natural Language Processing (2018)

Abstract Drilling activities in the oil and gas industry have been reported over decades for thousands of wells on a daily basis, yet little effort was made to analyze this text in large-scale for information retrieval, sequence mining, and pattern analysis. Drilling reports contain interpretations written by drillers from noting measurements in downhole sensors and surface equipment, and can be used for operation optimization and accident mitigation. In this initial work, a methodology is proposed for automatic classification of sentences written in drilling reports into three relevant labels (EVENT, SYMPTOM, and ACTION) for hundreds of wells in an actual field. Some of the main challenges in the text corpus were overcome, which include the high frequency of technical symbols, mistyping/abbreviation of technical terms, and the presence of incomplete sentences in the drilling reports. This work describes state-of-the-art classification accuracy obtained within this technical language and illustrates advanced queries enabled by the tool.
Human Monoclonal Antibodies Directed against Toxins A and B Prevent Clostridium difficile -Induced Mortality in Hamsters (2006)

Clostridium difficile is the leading cause of nosocomial antibiotic-associated diarrhea, and recent outbreaks of strains with increased virulence underscore the importance of identifying novel approaches to treat and prevent relapse of Clostridium difficile-associated diarrhea (CDAD). CDAD pathology is induced by two exotoxins, toxin A and toxin B, which have been shown to be cytotoxic and, in the case of toxin A, enterotoxic. In this report we describe fully human monoclonal antibodies (HuMAbs) that neutralize these toxins and prevent disease in hamsters. Transgenic mice carrying human immunoglobulin genes were used to isolate HuMAbs that neutralize the cytotoxic effects of either toxin A or toxin B in cell-based in vitro neutralization assays. Three anti-toxin A HuMAbs (3H2, CDA1, and 1B11) could all inhibit the enterotoxicity of toxin A in mouse intestinal loops and the in vivo toxicity in a systemic mouse model. Four anti-toxin B HuMAbs (MDX-1388, 103-174, 1G10, and 2A11) could neutralize cytotoxicity in vitro, although systemic toxicity in the mouse could not be neutralized. Anti-toxin A HuMAb CDA1 and anti-toxin B HuMAb MDX-1388 were tested in the well-established hamster model of C. difficile disease. CDA1 alone resulted in a statistically significant reduction of mortality in hamsters; however, the combination treatment offered enhanced protection. Compared to controls, combination therapy reduced mortality from 100% to 45% (P<0.0001) in the primary disease hamster model and from 78% to 32% (P<0.0001) in the less stringent relapse model.
Reaction of ketenes with N,N‐disubstituted α‐aminomethyleneketones. XVII. Synthesis of 2H‐[1]benzothiepino[5,4‐b]pyran derivatives (1986)

Abstract 1,4‐Cycloaddition of dichloroketene to a number of N , N ‐disubstituted ( E )‐4‐amino methylene‐3,4‐dihydro‐[1]benzothiepin‐5(2 H )‐ones gave in excellent yield N,N ‐disubstituted 4‐amino‐3,3‐dichloro‐3,4,5,6‐tetrahydro‐2 H ‐[1]benzothiepino[5,4‐ b ]pyran‐2‐ones III, which are derivatives of the 2 H ‐[1]benzothiepino[5,4‐ b ]pyran system. Dehydrochlorination of III with DBN afforded N,N ‐disubstituted 4‐amino‐3‐chloro‐5,6‐dihydro‐2 H ‐[1]‐benzothiepino[5,4‐ b ]pyran‐2‐ones, generally in excellent yield.
Recovery of CFU-GM from cryopreserved marrow and in vivo evaluation after autologous bone marrow transplantation are predictive of engraftment. (1986)

In 18 patients with non-Hodgkin's lymphomas or solid tumors treated with intensive chemotherapy and/or total-body irradiation followed by autologous bone marrow transplantation (ABMT), we assessed the value of granulocyte-macrophage progenitor cells (CFU-GM) monitoring to predict engraftment. We studied CFU-GM in cryopreserved marrow and attempted to settle whether detection of CFU-GM in vivo after ABMT has a predictive value on engraftment. Our data showed: The absence of linear correlation linking recovery of hematopoiesis to the dose of CFU-GM/kg infused. The existence of a CFU-GM threshold in respect to engraftment. Patients receiving doses of CFU-GM greater than 10(3)/kg had significantly faster recovery kinetics for hematopoiesis than did patients receiving doses below this threshold, with median recoveries to 0.5 and 1.0 X 10(9) neutrophils/liter, respectively, on days 14 and 15 versus days 29 and 31.5 (p less than 0.05 and p less than 0.02) and median recoveries to 1.0 and 2.5 X 10(9) leukocytes/liter respectively, on days 12.5 and 16 versus days 28 and 30.5 (p less than 0.05 and p less than 0.02). Considering the entire course of events during the first four weeks, we were able to show that white blood cell recovery was significantly faster in the group of patients receiving doses of CFU-GM greater than 10(3)/kg (p less than 0.001). Sequential studies of the reappearance of CFU-GM in marrow and peripheral blood indicated that the kinetics of CFU-GM recovery in vivo after ABMT predict engraftment. By day 7 after the graft, CFU-GM were already detectable in the marrow at a level of 10% of the dose infused for patients with optimal engraftment--median time to recovery to 1.0 and 2.5 X 10(9) leukocytes/liter and 1.0 X 10(9) neutrophils/liter on days 11, 15, and 14.5 versus days 18, 23, and 23 (p less than 0.02, less than 0.05, and less than 0.05), respectively after. On day 10 after ABMT, a 15% CFU-GM level in bone marrow confirmed engraftment, with a significant correlation of all parameters studied--1.0 and 2.5 X 10(9) leukocytes/liter (p less than 0.02 and less than 0.01), 0.5 and 1.0 X 10(9) neutrophils/liter (p less than 0.05), 50.0 and 100.0 X 10(9) platelets/liter (p less than 0.05). On day 14, a 50% CFU-GM level was reached in all patients with optimal engraftment; p less than 0.01 on 1.0, and 2.5 X 10(9) leukocytes on 0.5 and 1.0 X 10(9) neutrophils/liter. The detection of circulating CFU-GM in the blood by day 10 or 14 indicated engraftment.(ABSTRACT TRUNCATED AT 400 WORDS)
HiPAR-DSP: a parallel VLIW RISC processor for real time image processing applications (2002)

Derived from a thorough analysis of a wide class of image processing algorithms' properties, a parallel RISC architecture has been developed. The architecture gains performance from data level parallelism as well as from instruction level parallelism. From the beginning of the concept phase, high-level programming capabilities have been one of the major design goals. Thus, there has been a steady interaction between the design of the software development toolkit-optimizing assembler and C++ compiler-and the architecture itself. The RISC-typical register files are one of the most critical elements as well concerning die size and clock frequency as the assembler's ability in VLIW scheduling. Running at 100 MHz (200 mm/sup 2/, 0.35 /spl mu/m CMOS) the processor reaches a sustained performance of more than 2 GOPS for a wide range of image processing algorithms.