gebhart/patrepeval huggingface dataset:
End-to-End Applications and Algorithm Integration (E2A2I) Method and Architecture (2013)

DoD manned and unmanned air systems require multiple mission phases, each with unique procedures, algorithms and checklists that are implemented through a variety of hardware and software mechanisms, all within the same mission. This approach is not efficient with respect to mission processing, staffing, and training. The End-to-End Applications and Algorithm Integration (E2A2I) Method and Architecture addresses this issue using a checklist application that receives a complete mission checklist for all mission phases (e.g., pre-mission, launch and recovery, on-mission, post-mission, and maintenance) from a data broker enforcement entity that has access to a data store. This data store contains many checklists in support of multiple diverse missions. The E2A2I application automatically executes the checklists, invoking other mission applications in order of their mission usage. The E2A2I application runs on a mobile computing device with software services that invoke one mobile application from another so that the same applications can be used in multiple mission phases and for multiple missions.
Analysis of expressed sequence tags from Citrus sinensis L. Osbeck infected with Xylella fastidiosa (2007)

In order to understand the genetic responses resulting from physiological changes that occur in plants displaying citrus variegated chlorosis (CVC) symptoms, we adopted a strategy of comparing two EST libraries from sweet orange [Citrus sinensis (L.) Osbeck]. One of them was prepared with plants showing typical CVC symptoms caused by Xylella fastidiosa and the other with non-inoculated plants. We obtained 15,944 ESTs by sequencing the two cDNA libraries. Using an in silico hybridization strategy, 37 genes were found to have significant variation at the transcriptional level. Within this subset, 21 were up-regulated and 16 were down-regulated in plants with CVC. The main functional categories of the down-regulated transcripts in plants with CVC were associated with metabolism, protein modification, energy and transport facilitation. The majority of the up-regulated transcripts were associated with metabolism and defense response. Some transcripts associated with adaptation to stress conditions were up-regulated in plants with CVC and could explain why plants remain alive even under severe water and nutritional stress. Others of the up-regulated transcripts are related to defense response suggesting that sweet orange plants activate their defense machinery. The genes associated with stress response might be expressed as part of a secondary response related to physiological alterations caused by the infection.
The immunosuppressant rapamycin induces inactivation of p70s6k through dephosphorylation of a novel set of sites (1993)

The immunosuppressant rapamycin selectively abolishes phosphorylation and activation of p70s6k/p85s6k at concentrations that either block or suppress cell growth. The four sites of phosphorylation associated with p70s6k/p85s6k activation all display Ser/Thr-Pro motifs and are closely clustered within a putative autoinhibitory domain of the enzyme. To produce a constitutively active, rapamycin-resistant form of the kinase, these four sites were converted to either Asp or Glu. When overexpressed in human 293 cells, the activity of the mutant is similar to that of the parent enzyme, under conditions where the parent is phosphorylated and active. Unexpectedly, however, the mutant remains sensitive to rapamycin and is inactivated in vitro by protein phosphatase 2A. Peptide maps reveal that rapamycin abolishes the activity of the overexpressed p70s6k through the dephosphorylation of a novel set of sites distinct from those associated with mitogenic activation.
Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity (2019)

Chimeric antigen receptor T (CAR-T) cell therapy is an emerging and effective cancer immunotherapy. Especially in hematological malignancies, CAR-T cells have achieved exciting results. Two Anti-CD19 CAR-T therapies have been approved for the treatment of CD19-positive leukemia or lymphoma. However, the application of CAR-T cells is obviously hampered by the adverse effects, such as cytokines release syndrome and on-target off-tumor toxicity. In some clinical trials, patients quitted the treatment of CAR-T cells due to life-threatening toxicity. Seeking to alleviate these toxicities or prevent the occurrence, researchers have developed a number of safety strategies of CAR-T cells, including suicide genes, synthetic Notch receptor, on-switch CAR, combinatorial target-antigen recognition, bispecific T cell engager and inhibitory CAR. This review summarized the preclinical studies and clinical trials of the safety strategies of CAR-T cells and their respective strengths and weaknesses.
Matrix‐assisted laser desorption of large biomolecules with a TEA‐CO 2 ‐laser (1991)

Abstract Matrix‐assisted desorption/ionization of large biomolecules with a TEA‐CO 2 laser with a warelength of 10.6 μm is demonstrated. TEA‐CO 2 LDI mass spectra are almost identical to those obtained with the Er‐YAG (2.94 μm) infra‐red (IR) laser and very similar to UV‐LDI spectra. Most of the matrices usable for Er‐YAG IR‐LDI have been tested at 10.6 μm with success, and the main features of IR‐LDI e.g., the tendency towards the formation of higher chargers is shown.
Isolation of large numbers of enriched human megakaryocytes from liquid cultures of normal peripheral blood progenitor cells (1990)

Investigations linking human megakaryocyte development and cell biology have been hindered by an inability to obtain large, relatively pure megakaryocyte cell preparations from in vitro stem cell cultures. We report here that such preparations can be generated from liquid cultures of normal human peripheral blood mononuclear cells stimulated by a serum source of megakaryocyte colony stimulating activity (Meg-CSA, the 0% to 60% ammonium sulfate protein fraction of aplastic canine serum). Adherent-depleted peripheral blood mononuclear cells are suspended at 5 x 10(5) to 10(6) cells/mL in supplemented liquid culture medium, platelet-poor human plasma 20% (vol/vol) and 1 to 2 mg/mL serum Meg-CSA protein. After 12 to 14 days of incubation, megakaryocytes constitute 3.0 +/- 2.9% (mean +/- SD, n = 8) of the unseparated cultured cell population. Megakaryocytes can be enriched by counterflow centrifugal elutriation to a purity of 58 +/- 14% (+/- SD) with a recovery of 13 +/- 7% and a viability of 67 +/- 19%. This algorithm results in the average isolation of approximately 3 x 10(5) enriched megakaryocytes from a 100-mL starting volume of peripheral blood. Cultured megakaryocytes exhibit normal light and ultrastructural morphology by Wright-Giemsa staining and electron microscopic analysis. After a 12-day culture interval, enriched megakaryocyte preparations exhibit morphologic stage distributions that are similar to normal human marrow. Stage distributions move rightward with culture duration indicating partial synchrony of megakaryocyte maturation. On cytospin preparations, megakaryocyte diameter averages 30.2 +/- 1.5 microns and increases with maturation stage. Flow cytometric analyses demonstrate the expression of platelet glycoproteins (GP) Ib and IIb/IIIa by the cultured megakaryocytes. The modal ploidy of the enriched cells at day 12 of culture is 16N and most remaining megakaryocytes are 8N or 32N. Liquid culture of serum Meg-CSA-stimulated human peripheral blood mononuclear cells represents a valuable investigative tool that should permit studies of human megakaryocyte biology that have not been possible in the past.
Variations in Porphobilinogen and 5-Aminolevulinic Acid Concentrations in Plasma and Urine from Asymptomatic Carriers of the Acute Intermittent Porphyria Gene with Increased Porphyrin Precursor Excretion (2006)

The described HPLC-mass spectrometric method enabled characterization of variations in plasma PBG and ALA in AIP carriers during an 8-h period. The renal clearances were similar for both metabolites. This method could be used to monitor AIP patients during treatment.
Concordant evolution of coding and noncoding regions of DNA made possible by the universal rule of TA/CG deficiency-TG/CT excess. (1989)

The universal rule of TA/CG deficiency-TG/CT excess previously proposed as the construction principle of coding sequences applies to noncoding regions of the gene as well. Analysis of a 1989-base-long gene sequence for mouse immunoglobulin gamma 2a heavy-chain constant region as well as the 19,002-base-long gene sequence for human serum albumin revealed deficiency and overabundance of very similar sets of base trimers and tetramers in the coding and noncoding regions of the same gene, in spite of the fact that noncoding regions were considerably richer in A + T. Inasmuch as this universal rule does not discriminate one strand of DNA double helix from another, two complementary DNA strands of the entire gene maintained nearly perfect symmetry. That is to say, the degrees of excesses, deficiencies of the 64-base trimers remained nearly identical between two complementary strands, and this symmetry was only slightly disturbed in the coding region. It would thus appear that the universal rule as an intrinsic force has been exerting far greater influence than natural selection in the evolution of genes.
Designing siRNA That Distinguish between Genes That Differ by a Single Nucleotide (2006)

Small interfering RNAs (siRNAs), the guides that direct RNA interference (RNAi), provide a powerful tool to reduce the expression of a single gene in human cells. Ideally, dominant, gain-of-function human diseases could be treated using siRNAs that specifically silence the mutant disease allele, while leaving expression of the wild-type allele unperturbed. Previous reports suggest that siRNAs can be designed with single nucleotide specificity, but no rational basis for the design of siRNAs with single nucleotide discrimination has been proposed. We systematically identified siRNAs that discriminate between the wild-type and mutant alleles of two disease genes: the human Cu, Zn superoxide dismutase (SOD1) gene, which contributes to the progression of hereditary amyotrophic lateral sclerosis through the gain of a toxic property, and the huntingtin (HTT) gene, which causes Huntington disease when its CAG-repeat region expands beyond approximately 35 repeats. Using cell-free RNAi reactions in Drosophila embryo lysate and reporter assays and microarray analysis of off-target effects in cultured human cells, we identified positions within an siRNA that are most sensitive to mismatches. We also show that purine:purine mismatches imbue an siRNA with greater discriminatory power than other types of base mismatches. siRNAs in which either a G:U wobble or a mismatch is located in the "seed" sequence, the specialized siRNA guide region responsible for target binding, displayed lower levels of selectivity than those in which the mismatch was located 3' to the seed; this region of an siRNA is critical for target cleavage but not siRNA binding. Our data suggest that siRNAs can be designed to discriminate between the wild-type and mutant alleles of many genes that differ by just a single nucleotide.
Marker Discrimination in Transformation and Mutation of Pneumococcus (1973)

Earlier investigations of pneumococcal transformation revealed a function (hex(+)) responsible for severely reducing the transformation yield of certain markers. A mutational alteration (hex(-)) responsible for the loss of this function has been transferred into a hex(+) strain to permit a comparison of the hex(+) and hex(-) phenotypes in an isogenic background. The loss of the hex(+) function results both in a loss of the capacity to eliminate the low efficiency markers in transformation and a substantial increase in the spontaneous mutation rate. These properties of the hex(-) strain could result from the loss of a capacity to eliminate certain classes of mismatched base pairs that occur as intermediates in both transformation and mutagenesis.
Short‐Term Effects of Exogenous Angiotensin II on Plasma Fibrinolytic Balance in Normal Subjects (2004)

In conclusion, in healthy volunteer subjects, short-term infusion of Angiotensin II without and with concomitant administration of an AT1-receptor antagonist has no effect on PAI-1 activities and plasma concentrations.
Neutrophil--mediated cytotoxicity against tumour cells: state of art. (1992)

When activated by a variety of stimuli, human neutrophils become capable of lysing tumour cells. The main physiologic cytotoxic trigger in neutrophils is represented by the surface receptor for the Fc domain of IgG (FcR). This receptor confers specificity to the target recognition by neutrophils and cooperates with adhesion glycoproteins (CD11-CD18) in the neutrophil-target conjugate formation. Although the FcR-dependent pathways of signal transduction remain to be clarified, the neutrophil responses involve both the production of oxidants and the release of granule constituents. These molecules are responsible for the target lysis, whose extent also depends on the target structural and metabolic characteristics. The use of monoclonal antibodies specific for tumour cell antigens, coupled with appropriate cytokines, may provide rational basis for designing trials to employ the neutrophil cytotoxic potential as adjuvant therapy in cancer patients.
Synergistic interactions between interleukin 1, tumor necrosis factor, and lymphotoxin in bone resorption. (1987)

Cytokines with bone-resorbing activity include IL 1 beta (pI 7), IL 1 alpha (pI 5), tumor necrosis factor (TNF), and lymphotoxin (LT). Possible interaction between IL 1 beta, the major mediator with osteoclast-activating factor (OAF) activity, and other cytokines was studied. By itself, IL 1 beta was 13-fold more potent than IL 1 alpha and 1000-fold more potent than either TNF or LT in stimulating bone resorption. Suboptimal concentrations of IL 1 beta or IL 1 alpha in combination with suboptimal concentrations of TNF or LT resulted in synergistic bone-resorptive responses (1.5 to 10 times the expected responses if their effects were additive). Synergy between either form of IL 1 and TNF or LT resulted in a twofold increase in activity of IL 1, and a 100-fold increase in activity of TNF or LT. However, even with optimal synergy, IL 1 beta remained 20-fold more potent in inducing bone resorption than TNF or LT. Because IL 1 beta is considerably more potent than TNF and LT in stimulating bone resorption either alone or under synergistic conditions, it is unlikely that TNF and LT are responsible for more than a minor proportion of the total bone-resorbing activity formerly referred to as OAF.
Semiconductor hollow optical waveguides formed by omni-directional reflectors (2004)

In this study, a hollow optical waveguide with omni-directional reflectors in silicon-based materials was design, fabricated and characterized. By using dry etching technique, plasma-enhanced chemical vapor deposition for Si/SiO2 thin films and covering another wafer with omni-directional reflector together, the waveguides can be formed with an air core of 1.2microm x 1.3microm. A uniform propagation loss of the waveguide to be around 1.7dB/cm for C+L band was found for the TE and TM modes. Polarization-independent hollow optical waveguides were obtained with the hollow waveguide structure.
The Control of Oxidant Stress at Fertilization (1991)

Metazoan eggs alter their coats after fertilization to protect the early embryo. In sea urchins, this modification consists of a rapid, coordinated set of noncovalent macromolecular assembly steps that are stabilized by protein cross-linking. The sea urchin egg uses an oxidative cross-linking reaction that requires hydrogen peroxide and a secreted peroxidase and thus faces the challenge of oxidant stress at the beginning of its development. Protection from the deleterious effects of this oxidative mechanism is afforded by regulation of the production and utilization of oxidizing species. This regulation requires a specific protein kinase C-activated oxidase and ovothiol, an intracellular antioxidant.
Machine learning optimization of peptides for presentation by class II MHCs (2020)

Abstract T cells play a critical role in normal immune responses to pathogens and cancer and can be targeted to MHC-presented antigens via interventions such as peptide vaccines. Here, we present a machine learning method to optimize the presentation of peptides by class II MHCs by modifying the peptide’s anchor residues. Our method first learns a model of peptide affinity for a class II MHC using an ensemble of deep residual networks, and then uses the model to propose anchor residue changes to improve peptide affinity. We use a high throughput yeast display assay to show that anchor residue optimization successfully improved peptide binding.
5′RACE by Tailing a General Template-Switching Oligonucleotide (2000)

timized RAPD analysis generates high-quality genomic DNA profiles at high annealing temperature. Bi o Techniques 28 :52-54), an error was made in units of concentration. The dNTP concentration in Table
Serum sterols during stanol ester feeding in a mildly hypercholesterolemic population (1999)

We investigated the changes of cholesterol and non-cholesterol sterol metabolism during plant stanol ester margarine feeding in 153 hypercholesterolemic subjects. Rapeseed oil (canola oil) margarine without (n = 51) and with (n = 102) stanol (2 or 3 g/day) ester was used for 1 year. Serum sterols were analyzed with gas–liquid chromatography. The latter showed a small increase in sitostanol peak during stanol ester margarine eating. Cholestanol, campesterol, and sitosterol proportions to cholesterol were significantly reduced by 5–39% (P < 0.05 or less for all) by stanol esters; the higher their baseline proportions the higher were their reductions. The precursor sterol proportions were significantly increased by 10–46%, and their high baseline levels predicted low reduction of serum cholesterol. The decrease of the scheduled stanol dose from 3 to 2 g/day after 6-month feeding increased serum cholesterol by 5% (P < 0.001) and serum plant sterol proportions by 8–13% (P < 0.001), but had no consistent effect on precursor sterols. In twelve subjects, the 12-month level of LDL cholesterol exceeded that of baseline; the non-cholesterol sterol proportions suggested that stimulated synthesis with relatively weak absorption inhibition contributed to the non-responsiveness of these subjects. In conclusion, plant stanol ester feeding lowers serum cholesterol in about 88% of subjects, decreases the non-cholesterol sterols that reflect cholesterol absorption, increases the sterols that reflect cholesterol synthesis, but also slightly increases serum plant stanols. Low synthesis and high absorption efficiency of cholesterol results in the greatest benefit from stanol ester consumption.—Gylling, H., P. Puska, E. Vartiainen, and T. A. Miettinen. Serum sterols during stanol ester feeding in a mildly hypercholesterolemic population. J. Lipid Res. 1999. 40: 593–600.
Effect of Dutasteride on the Risk of Prostate Cancer (2010)

Over the course of the 4-year study period, dutasteride reduced the risk of incident prostate cancer detected on biopsy and improved the outcomes related to benign prostatic hyperplasia. (ClinicalTrials.gov number, NCT00056407.)
Monoclonal anti-idiotypic antibodies mimicking the immunodominant epitope of influenza virus haemagglutinin elicit biologically significant immune responses. (1998)

The MAb IIB4 recognizes an immunodominant epitope on influenza virus haemagglutinin (HA) which is shared by different strains of the human subtype H3. This epitope includes amino acids 198, 199 and 201, as determined by selection of IIB4 escape mutants, and is involved in haemagglutination-inhibition (HI) and virus-neutralization (VN). We have developed anti-idiotypic MAbs (Ab2) that mimic the IIB4 epitope. Two Ab2, 78 and 464, completely inhibited binding of MAb IIB4 to the virus. Nucleotide sequences of VL- and VH-encoding regions were determined for IIB4 and both Ab2. VH of IIB4 and 78 belong to the same IgG family (VII) and show high nucleotide identity (89%). Conversely, VH and VL sequences of both internal image-bearing Ab2 revealed lower degrees of identity (61 and 50%, respectively). Ab2 were used for syngeneic immunization to elicit polyclonal Ab3 responses. Like Ab1, Ab3 immunoprecipitated viral HA and displayed HI and VN activity. The different VN activity of anti-78 and anti-464 in vitro correlated with the affinities of their corresponding Ab2 to IIB4. In vivo immunization with either Ab2 protected 15-37% of mice against lethal influenza infection or delayed dying. In contrast to VN activity of Ab3 in vitro, there was no significant difference between the protection of mice induced by Ab2 78 and 464. We demonstrate, for the influenza model, that active immunization with a single influenza virus HA epitope in the form of its internal image leads to partial protection in vivo.
Modulation of Innate and Adaptive Immune Responses by Tofacitinib (CP-690,550) (2011)

Inhibitors of the JAK family of nonreceptor tyrosine kinases have demonstrated clinical efficacy in rheumatoid arthritis and other inflammatory disorders; however, the precise mechanisms by which JAK inhibition improves inflammatory immune responses remain unclear. In this study, we examined the mode of action of tofacitinib (CP-690,550) on JAK/STAT signaling pathways involved in adaptive and innate immune responses. To determine the extent of inhibition of specific JAK/STAT-dependent pathways, we analyzed cytokine stimulation of mouse and human T cells in vitro. We also investigated the consequences of CP-690,550 treatment on Th cell differentiation of naive murine CD4(+) T cells. CP-690,550 inhibited IL-4-dependent Th2 cell differentiation and interestingly also interfered with Th17 cell differentiation. Expression of IL-23 receptor and the Th17 cytokines IL-17A, IL-17F, and IL-22 were blocked when naive Th cells were stimulated with IL-6 and IL-23. In contrast, IL-17A production was enhanced when Th17 cells were differentiated in the presence of TGF-β. Moreover, CP-690,550 also prevented the activation of STAT1, induction of T-bet, and subsequent generation of Th1 cells. In a model of established arthritis, CP-690,550 rapidly improved disease by inhibiting the production of inflammatory mediators and suppressing STAT1-dependent genes in joint tissue. Furthermore, efficacy in this disease model correlated with the inhibition of both JAK1 and JAK3 signaling pathways. CP-690,550 also modulated innate responses to LPS in vivo through a mechanism likely involving the inhibition of STAT1 signaling. Thus, CP-690,550 may improve autoimmune diseases and prevent transplant rejection by suppressing the differentiation of pathogenic Th1 and Th17 cells as well as innate immune cell signaling.
Conversion of alkyl carbamates into amines via treatment with trimethylsilyl iodide (1978)

Reaction of the alkyl carbamates (1) with trimethylsilyl iodide (2) followed by methanolysis of the resulting trimethylsilyl carbamates (4), affords high yields of the corresponding amines (5), even in the case of very sensitive compounds such as 2,3-diazabicyclo[2.2.1]heptane (5h).
The Transforming Growth Factor‐Betas: A New Family of Immunoregulatory Molecules (1990)

Within the past three years there has been a rapid expansion in our knowledge of the role TGF-beta mediates in regulating immune responses in vitro. Whether the TGF-beta will be clinically useful to suppress immune responses to transplanted organs or autoimmune responses is unknown. However, now that highly purified quantities of TGF-beta are available through recombinant DNA technologies, questions concerning the in vivo immunosuppressive activities of TGF-beta can be answered.