gebhart/patrepeval huggingface dataset:
Roles for Innate Immunity in Combination Immunotherapies (2017)

Immunity to infectious agents involves a coordinated response of innate and adaptive immune cells working in concert, with many feed-forward and regulatory interactions between both arms of the immune system. In contrast, many therapeutic strategies to augment immunity against tumors have focused predominantly on stimulation of adaptive immunity. However, a growing appreciation of the potential contributions of innate immune effectors to antitumor immunity, especially in the context of combination immunotherapy, is leading to novel strategies to elicit a more integrated immune response against cancer. Here we review antitumor activities of innate immune cells, mechanisms of their synergy with adaptive immune responses against tumors, and discuss recent studies highlighting the potential of combination therapies recruiting both innate and adaptive immune effectors to eradicate established tumors. <i>Cancer Res; 77(19); 5215-21. ©2017 AACR</i>.
The Nine and Ten Year Results of the Low-Friction Arthroplasty of the Hip (1973)

This study of 9 and 10 years results of low-friction arthroplasty concerns operations performed from November 1962, when high density polyethylene for the hip socket was first introduced, to December 1963. This same series has been reported previously for 7 to 8 year results' but because we found it impossible to identify all the cases in the previous study it was considered advisable to go back to the original source material and, with a view to future studies of the ultimate fate of these patients, to identify all the material by: the initials of the name; the hospital number; the sex; and the age at time of operation. The protocols of all the hips in this study identified in this way are recorded in Table I.
A DETAILED ANALYSIS OF THE POTENTIAL OF WATER-SOLUBLE CLASSICAL CLASS I MHC MOLECULES FOR THE SUPPRESSION OF KIDNEY ALLOGRAFT REJECTION AND IN VITRO CYTOTOXIC T CELL RESPONSES (1989)

Water-soluble classical (RT1-A) class I MHC molecules were purified from aqueous extracts of DA strain liver. Following monoclonal antibody affinity, lentil lectin affinity, and gel filtration chromatography, 600 micrograms of soluble RT1-A class I molecules with antigen activity equivalent to 1.3 x 10(11) nucleated DA spleen cells (greater than 500 DA spleens) was obtained. Both PVG and LEW strain recipients of DA kidney allografts were pretreated with intravenous injections of the DA soluble class I molecules, in doses with antigen activity equivalent to 10(8) nucleated DA spleen cells. Three protocols of pretreatment were used: twice-weekly injections for 4-5 weeks, with grafting 3 or 4 days after the last injection; a single injection 7 days pregraft; or a single injection 1 day pregraft. The PVG and LEW rats received the soluble class I pretreatment either alone or in combination with suboptimal doses (2 mg/kg/day) of cyclosporine after grafting, making a total of 12 experimental groups treated with soluble class I antigen. In no case did treatment with soluble class I antigen elicit an antibody response in prospective graft recipients; influence kidney graft survival in any way; or enhance or suppress the antibody response to the kidney graft. The soluble DA class I MHC molecules were tested in vitro for their effect on the generation and effector function of allospecific PVG and LEW anti DA RT1-A class I cytotoxic T cells and TNP specific, self RT1-Aa restricted cytotoxic T cells. Concentrations up to 5 micrograms/ml (10(-7) M), equivalent to 10(9) nucleated DA spleen cells/ml, were without any effect. We conclude that monomeric forms of water-soluble classical class I molecules are poor immunogens--and, at doses conventionally used for active enhancement, do not influence cytotoxic T cell responses and have little potential for donor-specific immunosuppression.
Membrane-specific antibodies induced by liposomes can simultaneously bind to HIV-1 protein, peptide, and membrane lipid epitopes (2008)

Liposomes containing lipid A as an adjuvant and also containing either both (a) cholesterol and gp140 HIV envelope protein or (b) galactosylceramide and a 48 amino acid peptide from the membrane proximal external region of gp41 from HIV, as liposomal antigens were used for immunizing mice. Monoclonal antibodies from each type of immunization were obtained, which recognized either the lipid antigen or the protein (or peptide) antigen separately, or that simultaneously bound to both the lipid and protein (or peptide) antigens, by ELISA. After immunizing with liposomes containing both phosphatidylinositol 4-phosphate (PIP) and peptide antigen, a unique monoclonal antibody was also obtained, which did not bind separately either to the lipid or peptide antigen, or to the liposomes alone, but did bind to the original liposomal antigen containing the peptide but lacking PIP. Our data suggest that immunization with liposomes containing lipid A and also containing both a lipid and protein (or peptide) antigen induces antibodies that recognize broad topographical antigenic liposomal membrane surface patterns. These membrane-specific antibodies have unique binding characteristics.
Mechanisms and patterns of blood lactate increase during exercise in man (1986)

The close balance between the O2 requirement to perform exercise and the O2 supply was analyzed. A non-uniform capillary PO2 can result in anaerobic metabolism in some muscle fibers despite an apparently adequate mean capillary PO2. The pattern of lactate increase for constant work rates and incremental exercise is described. Lactate increases without an increase in pyruvate at a threshold work rate above which the lactate/pyruvate ratio increases. The latter decreases immediately at the start to recovery. From simultaneous measurements of arterial lactate and pyruvate during exercise and recovery, we conclude that the lactate increase at the lactate threshold is consequent to a change in redox state rather than a mass action effect.
Stacked inductors and 1-to-2 transformers in CMOS technology (2002)

A modification of stacked spiral inductors increases the self-resonance frequency by 100% with no additional processing steps, yielding values of 5 nH to 266 nH and self-resonance frequencies of 11.2 GHz to 0.5 GHz. Closed-form expressions predicting the self-resonance frequency with less than 5% error have also been developed. A 1-to-2 transformer consisting of 3 stacked spirals achieves a voltage gain of 1.8 at 2.5 GHz. The structures have been fabricated in standard CMOS technologies with four and five metal layers.
Trends in use of one, two, and three-line NCCNcategory 1 regimens among Medicare fee-for-service (FFS) patients receiving treatment for metastatic pancreatic cancer. (2021)

297 Background: There is limited research evaluating the share of patients (pts) with metastatic pancreatic cancer (m-PANC) treated according to NCCN guidelines. Methods: We identified pts with m-PANC using ICD-10 diagnosis codes in the 2016-2019 Medicare Parts A/B/D 100% Research Identifiable Files. Study pts had 2+ claims with a pancreatic cancer diagnosis and Medicare FFS coverage for 6 months pre- and 3 months post-metastatic disease diagnosis. A line of therapy (LOT) was assigned based on the order and number of therapies used. Pts with one, two, or three LOTs were defined as treated according to NCCN Category 1 guidelines if, in each LOT, pts used one of the following regimens: FOLFIRINOX (FFX), gemcitabine/nab-paclitaxel (gem/nab), gemcitabine + erlotinib, gemcitabine monotherapy, or 5-FU + leucovorin + liposomal irinotecan. Multi-drug LOTs were excluded from the analysis. Results: We identified 31,782 pts with m-PANC. 21,304 received one LOT, 7,352 received two LOTs, and 3,126 received three LOTs between 2016 and 2019. Among pts who received one or two LOTs, a higher portion were treated according to NCCN Category 1 guidelines in 2019 (72% and 43%, respectively) than in 2016 (64% and 33%, respectively). Among pts who received three LOTs, a higher portion were treated according to NCCN Category 1 guidelines in 2019 (17%) than in 2017 (12%); too few pts were treated in 2016 to make a comparison. From 2016 to 2019, FFX had the largest increase in share of pts receiving only one NCCN Category 1 LOT (11% to 27%) and gem-mono had the largest decrease (30% to 17%). Among pts receiving two NCCN Category 1 LOTs, gem/nab to liposomal irinotecan sequences had the largest increase in share of pts (18% to 32%) and gem/nab to FFX had the largest decrease (17% to 10%). Among pts receiving three NCCN Category 1 LOTs, patient share for FFX to gem/nab to Liposomal irinotecan was 35% in 2019, while gem/nab to FFX to Liposomal was 8%; pt counts in earlier years were too small to calculate patient share. Conclusions: The use of NCCN Category 1 therapies increased consistently from 2016 to 2019 among pts that received one, two, and three lines of therapy. FFX drove increases in NCCN Category 1 utilization among patients receiving one line of therapy, and gem/nab to liposomal irinotecan sequences were the primary drivers of the increase among patients receiving two lines of therapy. FFX to gem/nab to liposomal irinotecan was the primary driver of increase among patients receiving three lines of therapy.
The dermal-epidermal junction of human skin contains a novel laminin variant. (1992)

We report the identification of a novel laminin variant that appears to be unique to a subset of epithelial basement membranes. The variant contains two chains electrophoretically and immunologically identical to the B1 and B2 chains. Epitopes contained in the laminin A chain are absent from the molecule, and a 190-kD chain substitutes for the A chain. V8 protease analysis and Western blotting studies indicate that the variant 190-kD chain shows structural and immunological similarity to the 200-kD chain of kalinin. Rotary shadowing analysis indicates that the 190-kD chain contributes a large globular structure to the variant long arm, but lacks the short arm contributed to laminin by the A chain. The variant is produced by cultured skin explants, human keratinocytes and a squamous cell carcinoma line, and is present in human amniotic fluid. Polyclonal antibodies raised to kalinin, a recently characterized novel component of anchoring filaments, and mAb BM165 which recognizes a subunit of kalinin (Rousselle et al., 1991) cross react with the variant under nonreducing conditions. Immunohistological surveys of human tissues using the crossreacting antikalinin antiserum indicate that the distribution of this laminin variant is at least restricted to anchoring filament containing basement membranes. We propose the name K-laminin for this variant.
Development of an Aptamer-Based Concentration Method for the Detection of Trypanosoma cruzi in Blood (2012)

Trypanosoma cruzi, a blood-borne parasite, is the etiological agent of Chagas disease. T. cruzi trypomastigotes, the infectious life cycle stage, can be detected in blood of infected individuals using PCR-based methods. However, soon after a natural infection, or during the chronic phase of Chagas disease, the number of parasites in blood may be very low and thus difficult to detect by PCR. To facilitate PCR-based detection methods, a parasite concentration approach was explored. A whole cell SELEX strategy was utilized to develop serum stable RNA aptamers that bind to live T. cruzi trypomastigotes. These aptamers bound to the parasite with high affinities (8-25 nM range). The highest affinity aptamer, Apt68, also demonstrated high specificity as it did not interact with the insect stage epimastigotes of T. cruzi nor with other related trypanosomatid parasites, L. donovani and T. brucei, suggesting that the target of Apt68 was expressed only on T. cruzi trypomastigotes. Biotinylated Apt68, immobilized on a solid phase, was able to capture live parasites. These captured parasites were visible microscopically, as large motile aggregates, formed when the aptamer coated paramagnetic beads bound to the surface of the trypomastigotes. Additionally, Apt68 was also able to capture and aggregate trypomastigotes from several isolates of the two major genotypes of the parasite. Using a magnet, these parasite-bead aggregates could be purified from parasite-spiked whole blood samples, even at concentrations as low as 5 parasites in 15 ml of whole blood, as detected by a real-time PCR assay. Our results show that aptamers can be used as pathogen specific ligands to capture and facilitate PCR-based detection of T. cruzi in blood.
Inhibitory effects of antisense oligodeoxynucleotides targeting c-myc mRNA on smooth muscle cell proliferation and migration. (1993)

Smooth muscle cell (SMC) proliferation and migration play pivotal roles in restenosis following angioplasty. c-myc is an immediate early response gene induced by various mitogens, and several lines of evidence derived from experiments using transformed or hematopoietic cell lines, or transgenic mice, suggest its protein product plays a role in numerous signaling transduction pathways, including those modulating cell division. We therefore reasoned that a strategy employing oligodeoxynucleotides (ODNs) complementary to c-myc mRNA (antisense ODNs) might be potent inhibitors of SMC proliferation and, perhaps, of SMC migration. To evaluate this concept, we tested several antisense ODNs targeted to c-myc mRNA (15- or 18-mer ODNs complementary to different c-myc mRNA sequences) by introducing them individually into the medium of cultured rat aortic SMCs. Phosphoroamidate-modified ODNs were employed to retard degradation. Antisense ODNs inhibited, in a concentration-dependent manner, SMC proliferation and SMC migration. Maximal inhibitory effect was 50% for proliferation and &gt; 90% for migration. These effects were associated with decreased SMC expression of c-myc-encoded protein by Western immunoblotting and immunocytochemical staining. ODNs with the same nucleotides but a scrambled sequence caused no effect. These results indicate that the c-myc gene product is involved in the signal transduction pathways mediating SMC proliferation and migration in the in vitro model we employed. The results also suggest a potential role of antisense strategies designed to inhibit c-myc expression for the prevention of coronary restenosis.
Partial Suppression of Experimental Allergic Encephalomyelitis With Heparin (1972)

Experimental allergic encephalomyelitis in guinea pigs was partially suppressed with the administration of heparin sodium. Anticoagulating doses of heparin were required. Best results were obtained if heparin was given continually from time of immunization to the termination of the experiment. Some protection was also observed if heparin was given during either the first or the second week after immunization.
Predicting the Gas Diffusion Coefficient in Repacked Soil Water‐Induced Linear Reduction Model (2000)

Investigations of gas transport and fate processes in packed soil systems require knowledge of the gas diffusion coefficient, D P , as a function of air‐filled porosity, ϵ. On the basis of the literature, data from six studies over the porosity range of 0.1 to nearly 1.0, it is reconfirmed that the Marshall (1959) model better predicts D P (ϵ) in completely dry, repacked porous media than do the Penman (1940) and Millington (1959) models. The smaller D P value in wet soil, as compared with dry soil at the same air‐filled porosity, is accounted for by introducing a water‐induced linear reduction (WLR) term, equal to the ratio of air‐filled porosity to total porosity, in the D P (ϵ) model. By adding the WLR term in each of the three D P (ϵ) models for dry porous media, the so‐called WLR(Marshall), WLR(Penman), and WLR(Millington) D P (ϵ) models for wet soil are developed. To test the three WLR models, D P was measured at different soil‐water contents in six differently textured (6–38% clay) repacked soils. The WLR (Marshall) model accurately and best described D P (ϵ) for all six soils and additional soils from the literature. All three WLR models performed better than previous D P (ϵ) models. This study implies that the smaller D P in a wet soil, which is due to water‐induced changes in air‐filled pore shape and pore connectivity, can be described by a simple, linear function of relative air‐filled porosity. The WLR(Marshall) model represents a conceptual and accurate model to predict D P (ϵ) in sieved, repacked soil.
Characterization of monoclonal antibody fragments produced by plant cells (2001)

Production of a murine IgG1 was investigated using hairy roots, shooty teratomas, and suspended cells of transgenic tobacco. In all cases, in addition to complete assembled antibody, two to four major antibody fragments accumulated in the biomass. A range of protease inhibitors, protein-stabilizing agents, inhibitors of N-glycosylation and protein secretion, glycan-reactive agents, and affinity probes was used to characterize these fragments and investigate their sites and mechanisms of formation. The fragments were not experimental artifacts caused by antibody degradation during tissue homogenization and sample preparation, nor did they represent glycosylation variants. All of the molecules were actively secreted into the culture media and some showed evidence of Golgi-associated glycan processing, indicating they were not assembly intermediates. Antibody fragments of 50 and 80 kDa were identified mainly as the products of extracellular degradation in the root and shoot apoplast; the 80-kDa fragment was also present in cell suspension medium, and in suspended cell biomass toward the end of the growth phase. Larger 120- and 135-kDa fragments were most likely produced by proteolytic degradation along the secretory pathway outside of the endoplasmic reticulum (ER) and Golgi apparatus; the carbohydrate residues of the 135-kDa antibody suggest formation between these organelles. Inhibition of protein secretion and retention of antibody in the ER and/or Golgi reduced fragmentation and increased antibody accumulation levels, probably by reducing exposure to the principal sites of protease activity. This work highlights the importance of foreign protein degradation in plant tissues as a mechanism for posttranslational product loss. Identifying the nature of these degradative processes is a first step toward alleviating their effects, improving protein yields, and enhancing the feasibility of plants as a commercial means for large-scale protein production.
Highly Sensitive Multiple microRNA Detection Based on Fluorescence Quenching of Graphene Oxide and Isothermal Strand-Displacement Polymerase Reaction (2012)

A simple, highly sensitive, and selective multiple microRNA (miRNA) detection method based on the graphene oxide (GO) fluorescence quenching and isothermal strand-displacement polymerase reaction (ISDPR) was proposed. The capability to discriminate ssDNA and double-stranded nucleic acid structure coupled with the extraordinary fluorescence quenching of GO on multiple organic dye allows the proposed strategy to simultaneously and selectively detect several miRNA labeled with different dyes in the same solution, while the ISDPR amplification endows the detection method with high sensitivity. The strong interaction between ssDNA and GO led to the fluorescent ssDNA probe exhibiting minimal background fluorescence. Upon the recognition of specific target miRNA, an ISDPR was triggered to produce numerous massive specific DNA-miRNA duplex helixes, and a strong emission was observed due to the weak interaction between the DNA-miRNA duplex helix and GO. A miRNA biosensor down to 2.1 fM with a linear range of 4 orders of magnitude was obtained. Furthermore, the large planar surface of GO allows simultaneous quenching of several DNA probes with different dyes and produces a multiple biosensing platform with high sensitivity and selectivity, which has promising application in profiling the pattern of miRNA expression and biomedical research.
Determination of surface space–charge capacitance using a light probe (1982)

A new technique for the characterization of semiconductors, surface photovoltage measured capacitance (SPMC) is introduced. This technique permits the semiconductor surface space-charge capacitance to be determined by simple measurements of the intrinsic surface photovoltage (ISPV) induced by chopped light. ISPV transients for a semiconductor under depletion conditions are discussed. Both theoretical and experimental results are presented demonstrating the existence of two limiting dependences of the ISPV on the ratio Φ/f (photon flux divided by the chopping frequency of the incident light). It is shown that ISPV induced by low-intensity, high-frequency chopped light is proportional to the reciprocal of the semiconductor surface space-charge capacitance. This dependence is fundamental to the SPMC method whose capabilities are illustrated using GaAs. Using a three-electrode electrochemical cell, the doping concentration, the flat band potential and the energy of surface states which are responsible for the Fermi level pinning have been determined.
Automated Rule-Based Diagnosis Through a Distributed Monitor System (2007)

In today's world where distributed systems form many of our critical infrastructures, dependability outagesare becoming increasingly common. In many situations, it is necessary to not just detect a failure, but alsoto diagnose the failure, i.e., to identify the source of the failure. Diagnosis is challenging since highthroughput applications with frequent interactions between the different components allow fast errorpropagation. It is desirable to consider applications as black-boxes for the diagnostic process. In thispaper, we propose a Monitor architecture for diagnosing failures in large-scale network protocols. TheMonitor only observes the message exchanges between the protocol entities (PEs) remotely and doesnot access internal protocol state. At runtime, it builds a causal graph between the PEs based on theircommunication and uses this together with a rule base of allowed state transition paths to diagnose thefailure. The tests used for the diagnosis are based on the rule base and are assumed to have imperfectcoverage. The hierarchical Monitor framework allows distributed diagnosis handling failures at individualMonitors. The framework is implemented and applied to a reliable multicast protocol executing on ourcampus-wide network. Fault injection experiments are carried out to evaluate the accuracy and latency ofthe diagnosis.
Immunogenicity of transgenic plant-derived hepatitis B surface antigen. (1995)

The focus of the Children's Vaccine Initiative is to encourage the discovery of technology that will make vaccines more readily available to developing countries. Our strategy has been to genetically engineer plants so that they can be used as inexpensive alternatives to fermentation systems for production of subunit antigens. In this paper we report on the immunological response elicited in vivo by using recombinant hepatitis B surface antigen (rHBsAg) purified from transgenic tobacco leaves. The anti-hepatitis B response to the tobacco-derived rHBsAg was qualitatively similar to that obtained by immunizing mice with yeast-derived rHBsAg (commercial vaccine). Additionally, T cells obtained from mice primed with the tobacco-derived rHBsAg could be stimulated in vitro by the tobacco-derived rHBsAg, yeast-derived rHBsAg, and by a synthetic peptide that represents part of the a determinant located in the S region (139-147) of HBsAg. Further support for the integrity of the T-cell epitope of the tobacco-derived rHBsAg was obtained by testing the ability of the primed T cells to proliferate in vitro after stimulation with a monoclonal anti-idiotype and an anti-idiotype-derived peptide, both of which mimic the group-specific a determinant of HBsAg. In total, we have conclusively demonstrated that both B- and T-cell epitopes of HBsAg are preserved when the antigen is expressed in a transgenic plant.