gebhart/patrepeval huggingface dataset:
Stimulation of γδ T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma (2000)

Bisphosphonates are well-known inhibitors of osteoclastic bone resorption, but recent clinical reports support the possibility of direct or indirect antitumor effects by these compounds. Because bisphosphonates share structural homologies with recently identified γδ T-cell ligands, we examined the stimulatory capacity of bisphosphonates to γδ T cells and determined whether γδ T-cell stimulation by bisphosphonates could be exploited to generate antiplasma cell activity in multiple myeloma (MM). All tested aminobisphosphonates (alendronate, ibandronate, and pamidronate) induced significant expansion of γδ T cells (Vγ9Vδ2 subset) in peripheral blood mononuclear cell cultures of healthy donors at clinically relevant concentrations (half-maximal activity, 0.9-4 μmol/L). The proliferative response of γδ T cells to aminobisphosphonates was IL-2 dependent, whereas activation of γδ T cells (up-regulation of CD25 and CD69) occurred in the absence of exogenous cytokines. Pamidronate-activated γδ T cells produced cytokines (ie, interferon [IFN]-γ) and exhibited specific cytotoxicity against lymphoma (Daudi) and myeloma cell lines (RPMI 8226, U266). Pamidronate-treated bone marrow (BM) cultures of 24 patients with MM showed significantly reduced plasma cell survival compared with untreated cultures, especially in cultures in which activation of BM-γδ T cells was evident (14 of 24 patients with MM). γδ T-cell depletion from BM cultures completely abrogated the cytoreductive effect on myeloma cells in 2 of 3 tested patients with MM. These results show that aminobisphosphonates stimulating γδ T cells have pronounced effects on the immune system, which might contribute to the antitumor effects of these drugs.
Control of Cationic Conjugated Polymer Performance in Light Emitting Diodes by Choice of Counterion (2006)

Counterion exchange in cationic conjugated polyelectrolytes provides for a straightforward method to modulate the performance of these materials as the electron transport (injection) layer (ETL) in organic light emitting diodes. The bromide counterions of [(9,9-bis(6'-N,N,N-trimethylammonium)-hexyl)fluorene]bromide (PF-Br) can be easily replaced with trifluoromethylsulfonate (PF-CF3SO3), tetrakis(imidazolyl)borate (PF-BIm4) or tetrakis(3,5-trifluoromethylphenyl)borate (PF-BArF4) by a procedure that involves precipitation and washing. The performance of LEDs using MEH-PPV as the emissive layer, Al as the cathode, and the conjugated polyelectrolytes as the ETL varies in the order: PF-BIm4 > PF-CF3SO3 > PF-Br > PF-BArF4. In the case of PF-BIm4, the luminous efficiencies of the devices are similar to those of devices using Ba as the cathode. Thus, by properly choosing the counterion one can use higher work function metals that are more stable than lower work function metals without a substantial barrier to electron injection.
Measurement of IL-13–Induced iNOS-Derived Gas Phase Nitric Oxide in Human Bronchial Epithelial Cells (2007)

Exhaled nitric oxide (NO) is altered in numerous diseases including asthma, and is thought broadly to be a noninvasive marker of inflammation. However, the precise source of exhaled NO has yet to be identified, and the interpretation is further hampered by significant inter-subject variation. Using fully differentiated normal human bronchial epithelial (NHBE) cells, we sought to determine (1) the rate of NO release (flux, pl.s(-1.)cm(-2)) into the gas; (2) the effect of IL-13, a prominent mediator of allergic inflammation, on NO release; and (3) inter-subject/donor variability in NO release. NHBE cells from three different donors were cultured at an air-liquid interface and stimulated with different concentrations of IL-13 (0, 1, and 10 ng/ml) for 48 h. Gas phase NO concentrations in the headspace over the cells were measured using a chemiluminescence analyzer. The basal NO flux from the three donors (0.05 +/- 0.03) is similar in magnitude to that estimated from exhaled NO concentrations, and was significantly increased by IL-13 in a donor-specific fashion. The increase in NO release was strongly correlated with inducible nitric oxide synthase (iNOS) gene and protein expression. There was a trend toward enhanced production of nitrate relative to nitrite as an end product of NO metabolism in IL-13-stimulated cells. NO release from airway epithelial cells can be directly measured. The rate of release in response to IL-13 is strongly dependent on the individual donor, but is primarily due to the expression of iNOS.
Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. (1981)

The quantitative contributions of pancreatic responsiveness and insulin sensitivity to glucose tolerance were measured using the "minimal modeling technique" in 18 lean and obese subjects (88-206% ideal body wt). The individual contributions of insulin secretion and action were measured by interpreting the dynamics of plasma glucose and insulin during the intravenous glucose tolerance test in terms of two mathematical models. One, the insulin kinetics model, yields parameters of first-phase (phi 1) and second-phase (phi 2) responsivity of the beta-cells to glucose. The other glucose kinetics model yields the insulin sensitivity parameters, SI. Lean and obese subjects were subdivided into good (KG greater than 1.5) and lower (KG less than 1.5) glucose tolerance groups. The etiology of lower glucose tolerance was entirely different in lean and obese subjects. Lean, lower tolerance was related to pancreatic insufficiency (phi 2 77% lower than in good tolerance controls [P less than 0.03]), but insulin sensitivity was normal (P greater than 0.5). In contrast, obese lower tolerance was entirely due to insulin resistance (SI diminished 60% [P less than 0.01]); pancreatic responsiveness was not different from lean, good tolerance controls (phi 1: P greater than 0.06; phi 2: P greater than 0.40). Subjects (regardless of weight) could be segregated into good and lower tolerance by the product of second-phase beta-cell responsivity and insulin sensitivity (phi 2 . SI). Thus, these two factors were primarily responsible for overall determination of glucose tolerance. The effect of phi 1 was to modulate the KG value within those groups whose overall tolerance was determined by phi 2 . SI. This phi 1 modulating influence was more pronounced among insulin sensitive (phi 1 vs. KG, r = 0.79) than insulin resistant (obese, low tolerance; phi 1 vs. KG, r = 0.91) subjects. This study demonstrates the feasibility of the minimal model technique to determine the etiology of impaired glucose tolerance.
Long-term primary cultures of adult human and rat cardiomyocytes (1984)

An improved protocol for isolating and culturing adult mammalian cardiomyocytes is presented. Problems of establishing and maintaining cultured adult human and rat cardiomyocytes, and some of their properties, are discussed.
Producing Accurate Platelet Counts for Platelet Rich Plasma: Validation of a Hematology Analyzer and Preparation Techniques for Counting (2005)

Platelet rich plasma (PRP) has been shown to clinically accelerate healing of both soft and hard tissues. As a result, it has gained increasing popularity. However, the clinical effectiveness of each type of PRP preparation method can vary in technique and efficiency, and current methods to evaluate the platelet concentration efficiency of PRP systems have several limitations. Therefore, the purpose of this study was to validate an automated hematology analyzer, the Cell-Dyn 3700, to accurately count platelets in concentration ranges of approximately 2,000,000-4,800,000 platelets/microL. PRP platelets were counted by way of a manual counting method and on the Cell-Dyn 3700, and the statistical evaluation indicated no difference between the groups (P > 0.05). Dilution of the PRP was not required, and accurate platelet counts could be achieved up to platelet concentrations of 4,800,000 platelets/microL. PRPs must be resuspended on a rocker for at least 5 minutes before platelet counts, and the entire PRP sample must be resuspended to allow for equal distribution of platelets before counting. With use of the validated Cell-Dyn 3700, a platelet concentrate system was used to prepare 153 PRPs. The baseline whole blood platelet concentration (328,000 platelets/microL +/- 69,000 platelets/microL) and the average PRP samples (2,645,000 platelets/microL +/- 680,000 platelets/microL) were compared, resulting in an eightfold increase in concentration and an average platelet percent recovery of approximately 76%. Automated hematology analyzers can be used to accurately count platelets in PRP given the system has been validated appropriately and the PRP samples are prepared properly to provide adequate platelet suspension.
O‐Trifluoromethylation of N,N‐Disubstituted Hydroxylamines with Hypervalent Iodine Reagents (2014)

Abstract A mild trifluoromethylation reaction of N , N ‐disubstituted hydroxylamines that is tolerant towards a variety of functional groups, including nitriles, alcohols, ketones, esters, amides, imides, and nitrogen heterocycles, is reported. The key feature of this reaction is the activation of the CF 3 reagent with either trimethylsilyl triflate or LiClO 4 and partial or full deprotonation of the substrate with tetramethylguanidine or lithium diisopropylamide. Products were obtained in up to 80 % yield. Preliminary mechanistic studies suggested that the reaction follows a radical pathway in which the deprotonated hydroxylamine and a Lewis or Brønsted acid activated CF 3 reagent engages in a single‐electron‐transfer step to generate a pair of radicals that recombine to afford the desired product. The trifluoromethylation procedure was successfully used in the modification of secondary nitrogen groups of pharmaceutically relevant targets (Fluoxetine and Mefloquine), which afforded new derivatives containing a novel N ‐trifluoromethoxy moiety.
Pentoxifylline in Heart Failure: A Meta‐Analysis of Clinical Trials (2014)

A meta-analysis evaluating pentoxifylline versus placebo in HF suggested a significant nearly fourfold decrease in all-cause mortality in the pentoxifylline group.
A Bacillus subtilis dipeptide transport system expressed early during sporulation (1991)

Two previously identified Bacillus subtilis DNA segments, dciA and dciB, whose transcripts accumulate very rapidly after induction of sporulation, were found in the same 6.2 kb transcription unit, now known as the dciA operon. Analysis of the sequence of the dciA operon showed that its putative products are homologous to bacterial peptide transport systems. The product of the fifth gene, DciAE, is similar to peptide-binding proteins from Escherichia coli and Salmonella typhimurium (DppA and OppA) and B. subtilis (OppA). A null mutation in dciAE abolished the ability of a proline auxotroph to grow in a medium containing the dipeptide Pro-Gly as sole proline source, suggesting that the dciA operon encodes a dipeptide transport system.
Validation and comparison of two NGS assays for the detection of EGFR T790M resistance mutation in liquid biopsies of NSCLC patients (2018)

Analysis of circulating cell-free DNA (cfDNA) derived from peripheral blood ("liquid biopsy") is an attractive alternative to identify non-small cell lung cancer (NSCLC) patients with the <i>EGFR</i> T790M mutation eligible for 3rd generation tyrosine kinase inhibitor therapy. We evaluated two PCR-based next generation sequencing (NGS) approaches, one including unique molecular identifiers (UMI), with focus on highly sensitive <i>EGFR</i> T790M mutation detection. Therefore, we extracted and sequenced cfDNA from synthetic plasma samples spiked with mutated DNA at decreasing allele frequencies and from 21 diagnostic NSCLC patients. Data evaluation was performed to determine the limit of detection (LoD), accuracy, specificity and sensitivity of both assays. Considering all tested reference dilutions and mutations the UMI assay performed best in terms of LoD (1% vs. 5%), sensitivity (95.8% vs. 81.3%), specificity (100% vs. 93.8%) and accuracy (96.9% vs. 84.4%). Comparing mutation status of diagnostic samples with both assays showed 81.3% concordance with primary mutation verifiable in 52% of cases. <i>EGFR</i> T790M was detected concordantly in 6/7 patients with allele frequencies from 0.1% to 27%. In one patient, the T790M mutation was exclusively detectable with the UMI assay. Our data demonstrate that both assays are applicable as multi-biomarker NGS tools enabling the simultaneous detection of primary <i>EGFR</i> driver and resistance mutations. However, for mutations with low allelic frequencies the use of NGS panels with UMI facilitates a more sensitive and reliable detection.
Interleukin‐4 and Interferon‐γ: The Quintessence of a Mutual Antagonistic Relationship (1998)

The two cytokines interleukin (IL)-4 and interferon (IFN)-gamma play major roles in the generation and regulation of immune responses. Central in this respect is their mutually antagonistic functions. First, IL-4 promotes T helper cell type 2 (Th2) differentiation and stability and inhibits Th1-cell differentiation. A direct role of IFN-gamma in Th1-cell differentiation is debatable, whereas inhibition of Th2-cell differentiation and roles in Th1-cell stabilization are well established functions of IFN-gamma. Secondly, IL-4 and IFN-gamma also affect antibody class switch and expression of Fc receptors differentially, which strongly affect the effector mechanisms following antibody production. Thirdly, macrophage activities induced or enhanced by IFN-gamma, such as expression of certain cytokines, surface molecules and enzymes, are antagonized by IL-4. Together, these functions of IL-4 and IFN-gamma place the two cytokines at cardinal positions in the regulation of immune reactions. In this review the known molecular mechanisms underlying the observed functions of IL-4 and IFN-gamma are presented and discussed.
Effects of surgically and gastrically implanted radio transmitters on swimming performance and predator avoidance of juvenile chinook salmon (Oncorhynchus tshawytscha) (1998)

Radiotelemetry data are often used to make inferences about an entire study population; therefore, the transmitter attachment method should be the one that least affects the study animal. Juvenile chinook salmon (Oncorhynchus tshawytscha) &lt;120 mm in fork length (FL) with either gastrically or surgically implanted transmitters had significantly lower critical swimming speeds than control fish 1 and 19-23 days after tagging. For fish &gt;120 mm FL, fish with gastric implants swam as well as controls 1 day but not 19-23 days after tagging. In contrast, fish with surgical implants swam as well as controls 19-23 days but not 1 day after tagging. During predation trials, fish with gastric or surgical implants were eaten by smallmouth bass (Micropterus dolomieu) in significantly greater numbers than controls. We do not recommend implanting transmitters (representing 4.6-10.4% of the fish's body weight) in fish &lt;120 mm FL. Furthermore, surgical implants (representing 2.2-5.6% of the fish's body weight) may be the preferred method for biotelemetry studies of juvenile chinook salmon &gt;120 mm FL.
Encyclopedia of food science and technology (1992)

Citing the history and growth of the discipline, this encyclopaedia reflects recent changes in scientific and technical data. The principles and applications of food science and technology are discussed and current problems stressed include those associated with food additives and food spoilage. It presents a thorough alphabetical listing of articles dealing with the properties, analysis and processing of foods, including material on grains, beans, nuts, seeds, fruits and vegetables, bakery, dairy, meat, poultry and fish products, and alcoholic beverages.
Towards a quality of service model for replicated data access (2002)

This paper introduces the notion of a quality of service model for read and write access to a replicated database or file system. The goal is to provide clients with a choice of service guarantees and to separate the specification of a client's needs from the mechanisms implemented to meet those needs. An analogy is drawn with the quality of service models being explored for communications protocols.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Reversal of the Hofmeister Series: Specific Ion Effects on Peptides (2013)

Ion-specific effects on salting-in and salting-out of proteins, protein denaturation, as well as enzymatic activity are typically rationalized in terms of the Hofmeister series. Here, we demonstrate by means of NMR spectroscopy and molecular dynamics simulations that the traditional explanation of the Hofmeister ordering of ions in terms of their bulk hydration properties is inadequate. Using triglycine as a model system, we show that the Hofmeister series for anions changes from a direct to a reversed series upon uncapping the N-terminus. Weakly hydrated anions, such as iodide and thiocyanate, interact with the peptide bond, while strongly hydrated anions like sulfate are repelled from it. In contrast, reversed order in interactions of anions is observed at the positively charged, uncapped N-terminus, and by analogy, this should also be the case at side chains of positively charged amino acids. These results demonstrate that the specific chemical and physical properties of peptides and proteins play a fundamental role in ion-specific effects. The present study thus provides a molecular rationalization of Hofmeister ordering for the anions. It also provides a route for tuning these interactions by titration or mutation of basic amino acid residues on the protein surface.
Characterization of a Saccharomyces cerevisiae Mutant, N22, Defective in Ergosterol Synthesis and Preparation of [28-14C]Ergosta-5,7-dien-3β-ol with the Mutant1 (1983)

Analysis of sterols was made with a Saccharomyces cerevisiae mutant, N22, which was resistant to nystatin and defective in ergosterol synthesis, and with its parent strain, M10 (haploid type, methionineless, petite). The main sterol of M10 was ergosterol, whereas that of N22 was ergosta-5,7-dien-3 beta-ol. A small amount of ergosterol was found also in N22. This indicates that the delta 22-desaturation reaction in N22 is blocked, though not completely. Ergosta-5,8-dien-3 beta-ol, an unusual sterol, was detected in N22 but not in M10. Variations in the amounts and compositions of free and esterified sterols of both strains were examined during cultivation and the subsequent aerobic adaptation. The contents of free sterols, which were mostly composed of the respective main sterols of both strains, did not change markedly. In contrast, the contents and compositions of esterified sterols of both strains varied depending on the growth conditions. When the cells of both strains were aerobically adapted, the total contents of esterified sterols increase, as did, as the intermediate sterols. Upon aerobic adaptation in the presence of [methyl-14C]methionine, [28-14C]ergosta-5,7-dien-3 beta-ol accumulated markedly in N22 cells. Using this mutant, we devised a convenient method for preparation of the radioactive sterol in high yield.
Low temperature wafer bonding for micromechanical applications (1992)

A new class of modified silicon direct bonding processes is presented. The new process step within the bonding procedure involves the use of thin, intermediate layers to decrease the required process temperatures. The bonding process was characterized using oxidized silicon wafers. It was found that very strong bonds at temperatures around 200 degrees C or 350 degrees C can be achieved. Using ammonia-silica solutions, the surface energies achieve values of about 1.6 J/m/sup 2/. The lower bonding strength is compensated by offering a full IC-compatible bonding process. The influence of chemical and temperature treatment on the surface energies is described in detail.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Damage at hydrogenated amorphous/crystalline silicon interfaces by indium tin oxide overlayer sputtering (2012)

Damage of the hydrogenated amorphous/crystalline silicon interface passivation during transparent conductive oxide sputtering is reported. This occurs in the fabrication process of silicon heterojunction solar cells. We observe that this damage is at least partially caused by luminescence of the sputter plasma. Following low-temperature annealing, the electronic interface properties are recovered. However, the silicon-hydrogen configuration of the amorphous silicon film is permanently changed, as observed from infra-red absorbance spectra. In silicon heterojunction solar cells, although the as-deposited film's microstructure cannot be restored after sputtering, no significant losses are observed in their open-circuit voltage.
A design flow for configurable embedded processors based on optimized instruction set extension synthesis (2006)

Design tools for application specific instruction set processors (ASIPs) are an important discipline in systems-level design for wireless communications and other embedded application areas. Some ASIPs are still designed completely from scratch to meet extreme efficiency demands. However, there is also a trend, towards use of partially predefined, configurable RISC-like embedded processor cores that can be quickly tuned to given applications by means of instruction set extension (ISE) techniques. While the problem of optimized ISE synthesis has been studied, well from a theoretical perspective, there are still few approaches to an overall HW/SW design flow for configurable cores that take all real-life constraints into account In this paper, we therefore present a novel procedure for automated ISE synthesis that accommodates both user-specified and processor-specific constraints in a flexible wary and that produces value optimized ISE solutions in-short time. Driven by an advanced application C code analysis/profiling frontend, the ISE synthesis core algorithm is embedded into a complete, design flow, where the backend is formed by a state-of-the-art industrial tool for processor configuration, ISE IIW synthesis, and SW tool retargeting. The proposed, design flow, including ISE synthesis, is demonstrated, via several benchmarks for the MIPS CorExtend configurable RISC processor platform
Antibody-based therapy of leukaemia (2009)

Over the past decade, monoclonal antibodies have dramatically impacted the treatment of haematological malignancies, as evidenced by the effect of rituximab on the response rate and survival of patients with follicular and diffuse large B cell non-Hodgkin's lymphoma. Currently, only two monoclonal antibodies - the anti-CD33 immunotoxin gemtuzumab ozogamicin and the CD52-directed antibody alemtuzumab - are approved for treatment of relapsed acute myeloid leukaemia in older patients and B cell chronic lymphocytic leukaemia, respectively. Although not approved for such treatment, alemtuzumab is also active against T cell prolymphocytic leukaemia, cutaneous T cell lymphoma and Sézary syndrome, and adult T cell leukaemia and lymphoma. In addition, rituximab has demonstrated activity against B cell chronic lymphocytic and hairy cell leukaemia. Monoclonal antibodies targeting CD4, CD19, CD20, CD22, CD23, CD25, CD45, CD66 and CD122 are now being studied in the clinic for the treatment of leukaemia. Here, we discuss how these new antibodies have been engineered to reduce immunogenicity and improve antibody targeting and binding. Improved interactions with Fc receptors on immune effector cells can enhance destruction of target cells through antibody-dependent cellular cytotoxicity and complement-mediated cell lysis. The antibodies can also be armed with cellular toxins or radionuclides to enhance the destruction of leukaemia cells.