gebhart/patrepeval huggingface dataset:
Antibody-Dependent Enhancement of Dengue Virus Growth in Human Monocytes as a Risk Factor for Dengue Hemorrhagic Fever (1989)

Serum specimens collected during a prospective study of dengue infections among schoolchildren in Bangkok were tested for their ability to enhance dengue 2 (DEN-2) virus growth in human monocytes in vitro. Two groups of dengue-immune sera were compared: 32 dengue antibody positive serum specimens from children who subsequently developed asymptomatic secondary dengue infections; and 9 dengue antibody positive serum specimens from children who subsequently developed severe symptomatic secondary dengue infections, 8 of which were clinically diagnosed as dengue hemorrhagic fever. Antibody-dependent enhancement of virus growth was quantitated by measurement of virus yields in supernatant fluids of normal human monocyte cultures that were infected with DEN-2 virus in the presence of undiluted test serum. Only 4 of 32 (12%) preinfection sera from asymptomatic children, but 6 of 9 (67%) preinfection sera from symptomatic children, had significant enhancing activity (P less than 0.001). High serum DEN-2 antibody dependent enhancing activity is a significant (relative risk = 6.2) risk factor for severe illness among children in a dengue hemorrhagic fever endemic region. Dengue antibodies can be neutralizing and therefore protective, or they can be enhancing and increase the risk of dengue hemorrhagic fever.
Hydrogen Sulfide and Cell Signaling (2011)

Hydrogen sulfide (H₂S) is a gaseous mediator synthesized from cysteine by cystathionine γ lyase (CSE) and other naturally occurring enzymes. Pharmacological experiments using H₂S donors and genetic experiments using CSE knockout mice suggest important roles for this vasodilator gas in the regulation of blood vessel caliber, cardiac response to ischemia/reperfusion injury, and inflammation. That H₂S inhibits cytochrome c oxidase and reduces cell energy production has been known for many decades, but more recently, a number of additional pharmacological targets for this gas have been identified. H₂S activates K(ATP) and transient receptor potential (TRP) channels but usually inhibits big conductance Ca²(+)-sensitive K(+) (BK(Ca)) channels, T-type calcium channels, and M-type calcium channels. H₂S may inhibit or activate NF-κB nuclear translocation while affecting the activity of numerous kinases including p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), and Akt. These disparate effects may be secondary to the well-known reducing activity of H₂S and/or its ability to promote sulfhydration of protein cysteine moieties within the cell.
Synthesis, characterization, and controlled nitric oxide release from S‐nitrosothiol‐derivatized fumed silica polymer filler particles (2005)

A new type of nitric oxide (NO)-releasing material is described that utilizes S-nitrosothiols anchored to tiny fumed silica (FS) particles as the NO donor system. The synthetic procedures suitable for tethering three different thiol species (cysteine, N-acetylcysteine, and N-acetylpenicillamine) to the surface of FS polymer filler particles are detailed. The thiol-derivatized particles are converted to their corresponding S-nitrosothiols by reaction with t-butylnitrite. The total NO loading on the resulting particles range from 21-138 nmol/mg for the three different thiol-derivatized materials [S-nitrosocysteine-(NO-Cys)-FS, S-nitroso-N-acetylcysteine (SNAC)-FS, and S-nitroso-N-acetylpenicillamine (SNAP)-FS], with SNAP-FS yielding the highest NO loading. NO can be generated from these particles when suspended in solution via the addition of copper(II) ions, ascorbate, or irradiation with visible light. The SNAC-FS and SNAP-FS particles can be blended in polyurethane and silicone rubber matrixes to create films that release NO at controlled rates. Polyurethane films containing SNAC-FS submerged in phosphate-buffered saline (pH 7.4) generate NO surface fluxes approximately 0.1-0.7x10(-10) mol cm-2 min-1 and SNAP-FS films generate NO fluxes of approximately 0-7.5x10(-10) mol cm-2 min-1 upon addition of increasing amounts of copper ions. Silicone rubber films containing SNAC-FS or SNAP-FS do not liberate NO upon exposure to copper ions or ascorbate in phosphate-buffered saline solution. However, such films are shown to release NO at rates proportional to increasing intensities of visible light impinging on the films. Such photoinitiated NO release from these composite materials offers the first NO-releasing hydrophobic polymers with an external on/off trigger to control NO generation.
Extending a knowledge-based system to deal with ad hoc constraints (1981)

R1 is a rule based program used by Digital Equipment Corporation's manufacturing organization fc configuring VAX 11 systems. Since its inception. R1 has had the capability of producing a functional system by fleshing out an order consisting only of a CPU. some primary memory, and some devices; until recently, however, it was not capable of accepting as part of its input a set of ad hoc (customer specific) constraints Left to itself, R1 was capable of producing reasonable configurations. But it was incapable of modifying its decisions on the basis of information that others could provide This paper describes how rules were added to R1 to take advantage of such information R1 can now accept as input commands that specify how particular components are to be configured Whenever one of the commands becomes relevant, these rules take control, extend the configuration in the direction indicated by the command, and then step aside, allowing Rt's ordinary-case configuration rules to regain control.
SpCas9 activity prediction by DeepSpCas9, a deep learning–based model with high generalization performance (2019)

We evaluated SpCas9 activities at 12,832 target sequences using a high-throughput approach based on a human cell library containing single-guide RNA-encoding and target sequence pairs. Deep learning-based training on this large dataset of SpCas9-induced indel frequencies led to the development of a SpCas9 activity-predicting model named DeepSpCas9. When tested against independently generated datasets (our own and those published by other groups), DeepSpCas9 showed high generalization performance. DeepSpCas9 is available at http://deepcrispr.info/DeepSpCas9.
The Ovarian Artery as the Final Component of the Local Luteotropic Pathway Between a Gravid Uterine Horn and Ovary in Ewes (1976)

Fifty-five mature, cross-bred ewes which had been bred at estrus were used in 3 experiments. In Exp. 1, the role of the ovarian artery in the unilateral luteotropic effect of a gravid uterine horn was studied. On Days 5–7 after breeding the uterine horns were separated surgically in 16 bilaterally ovulating ewes. One uterine horn was left open to the abdominal cavity to produce a nongravid horn. Ewes were randomized into 4 groups: 1) unilaterally pregnant controls, 2) surgical anastomosis of ovarian branch of ovarian artery from a point near the ovary on the gravid side to the ovarian artery distant to the ovary (about 3 cm before bifurcation of artery) on the nongravid side, 3) nonpregnant controls in which the endometrium (and ability to produce luteolysin) on the gravid side was destroyed with phenol cautery, and 4) nonpregnant controls with phenol treatment (as in Group 3) and surgical anastomosis of ovarian artery (as in Group 2) from cauterized to nongravid side. At necropsy on Day 20, mean CL weights were less (P<0.01) on the nongravid side of Group 1 (117 mg) and on the noncauterized side of Groups 3 (171 mg) and4 (122 mg) than on the gravid side of Group 1 (542 mg), cauterized side of Group 3 (361 mg), and the nongravid side of Group 2 (722 mg). Mean CL weights were not significantly different among the nongravid side of Group 1 and the noncauterized side of Groups 3 and 4. The luteotropic (prevention of luteolysis) effect of a gravid uterine horn was studied in unilaterally ovulating ewes (Exp. 2 and 3). In Exp. 2, 28 bred ewes were randomized into a 2 × 2 factorial (sham-operation or hysterectomy × 0 or 200 μg PGF2α). Surgery was done on Days 5–7 and on Day 13 PGF2α or vehicle was infused into the ovarian artery on the CL side. On Day 15, mean CL weight was less (P<0.05) in hysterectomized ewes which were given 200μg (339 mg, CL regressed in 6/7 ewes) than in hysterectomized ewes which were given 0 μg (725 mg, CL regressed in 0/7 ewes) or in intact ewes which were given either 200 μg (540 mg, CL regressed in 2/7 ewes) or 0 μg (602 mg CL regressed in 1/7 ewes). There was no significant difference between doses in intact ewes. In Exp. 3, uterine horns were separated surgically on Days 5–7 and ewes were randomized into 2 groups: 1) surgical anastomosis of ovarian branch of ovarian artery from a point near the ovary on the nongravid side to a point near the ovary on the gravid side (6 ewes), 2) surgical anastomosis of ovarian branch of ovarian artery from a point near the ovary on the nongravid side to ovarian artery distant to ovary (as in Exp. 1) on the gravid side (5 ewes). Ewes were treated with progesterone in oil (25 mg daily) from Day 11 and necropsied on Day 18. Mean CL weight was less (P<0.05) in Group 1 ewes (410 mg, 2/6 ewes with maintained CL) than in Group 2 ewes (597 mg, 5/5 ewes with maintained CL). Results indicated that the gravid uterine horn exerts an antiluteolytic effect at the level of the adjacent ovary and that the effect is exerted through a local uteroovarian venoarterial pathway.
Nano- and micro-structured assemblies for encapsulation of food ingredients (2008)

This tutorial review provides an overview of the science of food materials and encapsulation techniques that underpin the development of delivery vehicles for functional food components, nutrients and bioactives. Examples of how the choice of materials, formulation and process affect the structure of micro- and nano-encapsulated ingredients and the release of the core are provided. The review is of relevance to chemists, material scientists, food scientists, engineers and nutritionists who are interested in addressing delivery challenges in the food and health industries.
An Empirical Codon Model for Protein Sequence Evolution (2007)

In the past, 2 kinds of Markov models have been considered to describe protein sequence evolution. Codon-level models have been mechanistic with a small number of parameters designed to take into account features, such as transition-transversion bias, codon frequency bias, and synonymous-nonsynonymous amino acid substitution bias. Amino acid models have been empirical, attempting to summarize the replacement patterns observed in large quantities of data and not explicitly considering the distinct factors that shape protein evolution. We have estimated the first empirical codon model (ECM). Previous codon models assume that protein evolution proceeds only by successive single nucleotide substitutions, but our results indicate that model accuracy is significantly improved by incorporating instantaneous doublet and triplet changes. We also find that the affiliations between codons, the amino acid each encodes and the physicochemical properties of the amino acids are main factors driving the process of codon evolution. Neither multiple nucleotide changes nor the strong influence of the genetic code nor amino acids' physicochemical properties form a part of standard mechanistic models and their views of how codon evolution proceeds. We have implemented the ECM for likelihood-based phylogenetic analysis, and an assessment of its ability to describe protein evolution shows that it consistently outperforms comparable mechanistic codon models. We point out the biological interpretation of our ECM and possible consequences for studies of selection.
Finding your way in the testing jungle: a learning approach to web security testing (2013)

Black-box security testing of web applications is a hard problem. The main complication lies in the black-box assumption: The testing tool has limited insight into the workings of server-side defenses. This has traditionally led commercial as well as research vulnerability scanners toward heuristic approaches, such as testing each input point (e.g. HTTP parameter) with a short, predefined list of effective test payloads to balance between coverage and performance.
Isolation and partial purification of a novel anticoagulant from arteries of human umbilical cord (1985)

An anticoagulant fraction was isolated from the homogenate of human umbilical cord arteries, using Sephadex gel filtration and DEAE-Sephacel chromatography. Analysis with dodecyl sulfate/polyacrylamide gel electrophoresis and inactivation studies using proteolytic enzymes indicate that the anticoagulant activity is associated with a polypeptide with an apparent Mr of 32 000. The anticoagulant inhibits thromboplastin as well as factor Xa induced clotting but does not affect thrombin initiated fibrin formation. The anticoagulant inhibits the activation of prothrombin by the complete prothrombinase complex, by phospholipid bound factor Xa but not by free factor Xa. The inhibition is instantaneous and independent of the incubation time over the whole range of concentrations tested. Therefore, the anticoagulant is unlikely to be a phospholipase or a protease. Its action does not resemble that of the plasma protease inhibitors, but it probably interferes with the phospholipid--clotting factor interactions.
Anti-inflammatory Properties of Cytochrome P450 Epoxygenase-Derived Eicosanoids (1999)

The epoxyeicosatrienoic acids (EETs) are products of cytochrome P450 epoxygenases that have vasodilatory properties similar to that of endothelium-derived hyperpolarizing factor. The cytochrome P450 isoform CYP2J2 was cloned and identified as a potential source of EETs in human endothelial cells. Physiological concentrations of EETs or overexpression of CYP2J2 decreased cytokine-induced endothelial cell adhesion molecule expression, and EETs prevented leukocyte adhesion to the vascular wall by a mechanism involving inhibition of transcription factor NF-kappaB and IkappaB kinase. The inhibitory effects of EETs were independent of their membrane-hyperpolarizing effects, suggesting that these molecules play an important nonvasodilatory role in vascular inflammation.
GABAergic innervation of alpha type II calcium/calmodulin‐dependent protein kinase immunoreactive pyramidal neurons in the rat basolateral amygdala (2002)

Although calcium/calmodulin-dependent protein kinase II (CaMK) has been shown to play a critical role in long-term potentiation (LTP) and emotional learning mediated by the basolateral amygdala, little is known about its cellular localization in this region. We have utilized immunohistochemical methods to study the neuronal localization of CaMK, and its relationship to gamma-aminobutyric acid (GABA)-ergic structures, in the rat basolateral amygdala (ABL). Light microscopic observations revealed dense CaMK staining in the ABL. Although the cell bodies and proximal dendrites of virtually every pyramidal cell appeared to be CaMK(+), the cell bodies of small nonpyramidal neurons were always unstained. Dual localization of CaMK and GABA immunoreactivity with confocal immunofluorescence microscopy revealed that CaMK and GABA were found in different neuronal populations in the ABL. CaMK was contained only in pyramidal neurons; GABA was contained only in nonpyramidal cells. At the ultrastructural level, it was found that CaMK was localized to pyramidal cell bodies, thick proximal dendrites, thin distal dendrites, most dendritic spines, axon initial segments, and axon terminals forming asymmetrical synapses. These findings suggest that all portions of labeled pyramidal cells, with the exception of some dendritic spines, can exhibit CaMK immunoreactivity. By using a dual immunoperoxidase/immunogold-silver procedure at the ultrastructural level, GABA(+) axon terminals were seen to innervate all CaMK(+) postsynaptic domains, including cell bodies (22%), thick (>1 microm) dendrites (34%), thin (<1 microm) dendrites (22%), dendritic spines (17%), and axon initial segments (5%). These findings indicate that CaMK is a useful marker for pyramidal neurons in ultrastructural studies of ABL synaptology and that the activity of pyramidal neurons in the ABL is tightly controlled by a high density of GABAergic terminals that target all postsynaptic domains of pyramidal neurons.
Cell therapies for type 1 diabetes mellitus (2004)

Type 1 diabetes is caused by autoimmune destruction of pancreatic β-cells and is characterised by absolute insulin insufficiency. The monocellular nature of this disease and endocrine action of insulin make this disease an excellent candidate for cellular therapy. Furthermore, precedent for cellular therapies has been set by successful cadaveric whole pancreas and islet transplantation. In order to expand the supply of cells to meet current and future needs, several novel cell sources have been proposed, including human β-cells or islets expanded in culture, islet xenografts and pancreatic ductal progenitor cells. Surrogate β-cells derived from hepatocytes, intestinal K cells or non-endodermal cell types have also been suggested. Stem cells found in bone marrow and umbilical cord blood have been used extensively to repopulate the haematopoietic system and offer the possibility of autologous transplantation. Recent studies have suggested that these stem cells may also have a broader capacity to differentiate, possibly into β-cells. Stem cells from embryonic sources, such as human embryonic stem and embryonic germ cells, have the ability to proliferate extensively in culture and have an inherent developmental plasticity that may make them a potentially unlimited source of cells that can sense glucose and produce mature insulin. The wide range of proposed cell sources and our increasingly clear picture of pancreatic development suggest that novel cellular therapies might one day compete with non-cellular glucose sensing and insulin delivery devices.
Quality Characteristics and Antioxidants of Mavrolia cv. Virgin Olive Oil (2011)

Abstract The quality characteristics and bioactive microconstituents of virgin olive oil produced by Mavrolia cv, an Olea europaea variety grown in Southern Peloponnesus, Greece, are reported for the first time. The oil samples of Mavrolia cv. studied fell within the limits established for the extra virgin olive oil (EVOO) category and were characterized by higher levels of campesterol (88.7 ± 14.8 vs. 56.1 ± 6.1 mg kg −1 oil) and β‐sitosterol (1692.6 ± 100.3 vs. 1356.2 ± 85 mg kg −1 oil) and relatively lower oxidative stability (19.35 ± 2.62 vs. 37.44 ± 1.97 h) compared to Koroneiki cv. The lower oxidative stability was positively correlated to significantly lower polyphenols (88.95 ± 2.33 vs. 233.75 ± 34.29) and α‐tocopherol (517.2 ± 6.50 vs. 655.37 ± 17.78) and to higher polyunsaturated fatty acids content (9.27 ± 0.35 vs. 6.41 ± 0.38). Tyrosol, ferulic acid and protocatechuic acid contents were significantly higher in Mavrolia cv. samples compared to Koroneiki cv. (218.80 ± 44.8 vs. 83.7 ± 23.1, 1.82 ± 0.11 vs. 0.97 ± 0.31, and 1.55 ± 0.39 vs. 0.35 ± 0.60 mg kg −1 , respectively). Also, the bitter and pungent attributes were found in lower intensities compared to Koroneiki cv. EVOO for the same period (1.9 vs. 2.5 and 2.3 vs. 3.9, respectively). The ripe fruity intensity with walnut olfactory attribute of the Mavrolia cv., was also light to medium.
Activation of platelet heparitinase by tumor cell-derived factors (1991)

The nature of the cooperation between platelets and tumor cells during the process of blood-borne metastasis is essentially unknown. In previous in vitro studies we showed that platelets participated in the formation of gaps in the endothelial cell lining, and that concomitantly heparan sulfate glycosaminoglycans were degraded by the platelet heparitinase, released on activation of platelets. In the current study we show that the ability to degrade proteoheparan sulfate derived from endothelial extracellular matrix is gradually eliminated when the number of human platelets is decreased from 5 x 10(7) to 10(6) cells/mL. When aliquots of conditioned media or lysates of either Eb or heat-inactivated ESb mouse lymphoma cells (both of which showed no heparanase activity) were added to freeze-thawed lysates of 10(6) platelets, a reappearance of platelet heparitinase activity was observed. A similar activation was not elicited by lysates of several normal mammalian cells. These data suggest that in its native form, a fraction of the platelet heparitinase is stored in an inactive form that can be activated by a factor secreted by lymphoma, but not by normal cells. Partial characterization of the heparitinase-activating factor showed that it is a heat-stable polyanionic molecule, devoid of proteolytic activity and resistant to both proteolytic and chondroitinase digestions. Activation of platelet heparitinase was also observed on coincubation with chondroitinases ABC and AC, suggesting that the inactive form of platelet heparitinase could result from a complex formation with a chondroitinase-sensitive proteoglycan. The lymphoma-derived heparitinase activating factor itself is, however, not a chondroitinase, because activity of chondroitinase could not be detected in Eb and ESb cells. A possible mechanism by which tumor cells recruit and regulate the activity of platelet heparitinase, and its relevance to the progression of blood borne metastasis, is discussed.
Hypoxia and Aggressive Tumor Phenotype: Implications for Therapy and Prognosis (2008)

Tumor hypoxia, mostly resulting from poor perfusion and anemia, is one of the key factors in inducing the development of cell clones with an aggressive and treatment-resistant phenotype that leads to rapid progression and poor prognosis. Studies in patients with solid tumors suggest that there is a range of hemoglobin (Hb) concentrations that is optimum for tumor oxygenation. When used to achieve an Hb level within this range, erythropoiesis-stimulating agents (ESAs) can be expected to increase tumor oxygenation, and this may favorably influence sensitivity to treatment as well as quality of life. There is no robust evidence that ESAs, when used as indicated, have a negative effect on survival in patients with solid tumors. When used outside the indications recommended, the rise in Hb level that results may reduce tumor blood flow and tissue oxygenation because of a raised viscosity within the abnormal tumor microvasculature. In the current situation, it remains important to use ESAs within the approved indications and according to treatment guidelines such as those developed by the European Organization for Research and Treatment of Cancer.