gebhart/patrepeval huggingface dataset:
Mechanisms of action of ruxolitinib in murine models of hemophagocytic lymphohistiocytosis (2019)

Hemophagocytic lymphohistiocytosis (HLH) is an often-fatal disorder characterized by the overactivation of T cells and macrophages that excessively produce proinflammatory cytokines, including interferon-γ (IFN-γ). Previously, we reported that the JAK inhibitor ruxolitinib dampens T-cell activation and lessens inflammation in a model of HLH in which perforin-deficient (<i>Prf1</i> <sup>-/-</sup>) mice are infected with lymphocytic choriomeningitis virus (LCMV). Ruxolitinib inhibits signaling downstream of IFN-γ, as well as several other JAK-dependent cytokines. As a consequence, it remained unclear whether ruxolitinib was exerting its beneficial effects in HLH by inhibiting IFN-γ signaling or by targeting signaling initiated by other proinflammatory cytokines. To address this question, we compared the effects of ruxolitinib with those obtained using an IFN-γ-neutralizing antibody (αIFN-γ) in 2 murine HLH models. In both models, ruxolitinib and αIFN-γ reduced inflammation-associated anemia, indicating that ruxolitinib operates in an IFN-γ-dependent manner to reverse this HLH manifestation. In contrast, the number and activation status of T cells and neutrophils, as well as their infiltration into tissues, were significantly reduced following treatment with ruxolitinib, but they remained unchanged or were increased following treatment with αIFN-γ. Notably, despite discontinuation of ruxolitinib, LCMV-infected <i>Prf1</i> <sup>-/-</sup> mice exhibited enhanced survival compared with mice in which αIFN-γ was discontinued. This protective effect could be mimicked by transient treatment with αIFN-γ and a neutrophil-depleting antibody. Thus, ruxolitinib operates through IFN-γ-dependent and -independent mechanisms to dampen HLH by targeting the deleterious effects of T cells and neutrophils, with the latter representing an unappreciated and understudied cell type that contributes to HLH pathogenesis.
Photochemical Reactions of Alkyl Phenylglyoxylates1 (1996)

Three new photoproducts, ethyl O-benzoyl mandelate (5a), ethyl O-acetylmandelate (6a), and biphenyl triketone (7a) are isolated and identified in the reactions of ethyl phenylglyoxylate (1a) in benzene. Quantum yields and initial rate constants of product formation are shown to be concentration dependent. For the formation of carbonyl product 3 at lower starting material concentrations (<0.01 M), quantum yields greater than 1 are observed. Variations in the quantum yields as a function of reaction time are due to the accumulation of alpha-hydroxyphenyl ketene (D). The relative reactivities of triplet excited states of phenylglyoxylates 1 and phenyl ketones are compared. A mechanism involving both intramolecular gamma-H abstraction and intermolecular H abstraction, which leads to radical chain reaction, is proposed. Rate constants for intramolecular gamma-H abstraction (k(N)) and intermolecular H abstraction (k(I)) of methyl phenylglyoxylate (1d) are measured.
Flammability Properties of Polymer−Layered-Silicate Nanocomposites. Polypropylene and Polystyrene Nanocomposites (2000)

Our continuing study of the mechanism of flammability reduction of polymer−layered-silicate nanocomposites has yielded results for polypropylene-graft-maleic anhydride and polystyrene−layered-silicate nanocomposites using montmorillonite and fluorohectorite. Cone calorimetry was used to measure the heat release rate and other flammability properties of the nanocomposites, under well-controlled combustion conditions. Both the polymer−layered-silicate nanocomposites and the combustion residues were studied by transmission electron microscopy and X-ray diffraction. We have found evidence for a common mechanism of flammability reduction. We also found that the type of layered silicate, nanodispersion, and processing degradation have an influence on the flammability reduction.
Saturated double‐angle method for rapid B1+ mapping (2006)

For in vivo magnetic resonance imaging at high field (> or =3 T) it is essential to consider the homogeneity of the active B(1) field (B(1)+), particularly if surface coils are used for RF transmission. A new method is presented for highly rapid B(1)+ magnitude mapping. It combines the double angle method with a B(1)-insensitive magnetization-reset sequence such that the choice of repetition time (TR) is independent of T(1) and with a multislice segmented (spiral) acquisition to achieve volumetric coverage with adequate spatial resolution in a few seconds. Phantom experiments confirmed the accuracy of this technique even when TR << T(1), with the side effect being lowered SNR. The speed of this method enabled B(1)+ mapping in the chest and abdomen within a single breath-hold. In human cardiac imaging, the method enabled whole-heart coverage within a single 16-s breath-hold. Results from phantoms and healthy volunteers at 1.5 T and 3 T are presented.
A New VISTA on combination therapy for negative checkpoint regulator blockade (2016)

Negative checkpoint regulators function to restrain T cell responses to maintain tolerance and limit immunopathology. However, in the setting of malignancy, these pathways work in concert to promote immune-mediate escape leading to the development of a clinically overt cancer. In the recent years, clinical trials demonstrating the efficacy of blocking antibodies against these molecules have invigorated the field of immunotherapy. In this review, we discuss the current understanding on established NCR blockade and how strategic combination therapy with anti-VISTA antibody can be used to target multiple non-redundant NCR pathways.
Regulation of the glyoxylate bypass operon: cloning and characterization of iclR (1990)

In Escherichia coli, expression of the glyoxylate bypass operon appears to be controlled, in part, by the product of iclR+. Mutations in iclR have been found to yield constitutive expression of this operon, suggesting that iclR+ encodes a repressor protein. We have cloned iclR+ by taking advantage of its tight genetic linkage with the glyoxylate bypass operon. The clone complemented a mutant allele of iclR in trans, restoring an inducible phenotype for this operon. Deletion analysis identified a region of ca. 900 base pairs that was necessary and sufficient for complementation. The nucleotide sequence of the insert was then determined. Translation of this sequence revealed an open reading frame capable of encoding a protein with Mr 29,741 preceded by a potential Shine-Dalgarno ribosome-binding site. The deduced amino acid sequence includes a region at the amino terminus that may form a helix-turn-helix motif, a structure found in many DNA-binding domains.
Cutting Edge: Interleukin 17 Signals through a Heteromeric Receptor Complex (2006)

IL-17 is an inflammatory cytokine produced primarily by a unique lineage of CD4 T cells that plays critical roles in the pathogenesis of multiple autoimmune diseases. IL-17RA is a ubiquitously expressed receptor that is essential for IL-17 biologic activity. Despite widespread receptor expression, the activity of IL-17 is most classically defined by its ability to induce the expression of inflammatory cytokines, chemokines, and other mediators by stromal cells. The lack of IL-17 responsiveness in mouse stromal cells genetically deficient in IL-17RA is poorly complemented by human IL-17RA, suggesting the presence of an obligate ancillary component whose activity is species specific. This component is IL-17RC, a distinct member of the IL-17R family. Thus, the biologic activity of IL-17 is dependent on a complex composed of IL-17RA and IL-17RC, suggesting a new paradigm for understanding the interactions between the expanded family of IL-17 ligands and their receptors.
Exploring the functions of RNA interference pathway proteins: some functions are more RISCy than others? (2005)

PPD (PAZ Piwi domain) proteins and the Dicer family have been the subjects of intense study over the last 6 years. These proteins have well-established roles in RNAi (RNA interference), a process that relies on siRNAs (small interfering RNAs) or miRNAs (microRNAs) to mediate specificity. The development of techniques for applying RNAi as a laboratory tool and a molecular therapeutic technique has rapidly outpaced our understanding of the biology of this process. However, over the last 2 years, great strides have been made towards elucidating how PPD proteins and Dicer regulate gene-silencing at the pre- and post-transcriptional levels. In addition, evidence is beginning to emerge that suggests that these proteins have additional siRNA-independent roles as cell-cycle regulators. In the present review, we summarize the well-known roles of these two classes of proteins in gene-silencing pathways, as well as explore the evidence for novel roles of PPD and Dicer proteins.
NK Cells Lose Their Inhibition (2004)

Hepatitis C virus (HCV) infects more than 180 million people worldwide and can lead to liver failure or liver cancer later in life. As
 Parham
 discusses in his thought-provoking Perspective, a step toward understanding how the human immune system resolves HCV infection and to developing a vaccine has been made with the finding that infected individuals of a particular genotype more readily resolve HCV infection than infected individuals of other genotypes (
 Khakoo
 et al.).
Prediction of Equilibrium Partitioning of Nonpolar Organic Solutes in Water‐ Surfactant Systems by UNIFAC and COSMO‐RS Models (2006)

Abstract In the present study the potential of two thermodynamic‐based models (the group‐contribution UNIFAC model and the a priori predictive COSMO‐RS model) to predict solute partitioning in aqueous surfactant solutions is evaluated. In order to take into account the small size of micelles, the UNIFAC model was extended by the interfacial contribution based on the Gibbs‐Thompson equation. The applicability of the approach was successfully proved for the partitioning of nonpolar solutes (toluene, p‐xylene) in aqueous solutions of nonionic surfactants. The original COSMO‐RS model underestimates the concentration of the solute in the aqueous phase in the case of micellar systems since it does not account for the small size of micelles. At the same time, this model gives quantitative results for the octanol/water partition coefficients of both solutes under study leading to the conclusion that the affinity of both solutes to a certain solvent is well described. Thus, extending the COSMO‐RS by the interfacial term seems to be promising.
Scalable Network Virtualization in Software-Defined Networks (2013)

Network virtualization gives each "tenant" in a data center its own network topology and control over its traffic flow. Software-defined networking offers a standard interface between controller applications and switch-forwarding tables, and is thus a natural platform for network virtualization. Yet, supporting numerous tenants with different topologies and controller applications raises scalability challenges. The FlowN architecture gives each tenant the illusion of its own address space, topology, and controller, and leverages database technology to efficiently store and manipulate mappings between virtual networks and physical switches.
On-site variety discrimination of tomato plant using visible-near infrared reflectance spectroscopy (2009)

The use of visible-near infrared (NIR) spectroscopy was explored as a tool to discriminate two new tomato plant varieties in China (Zheza205 and Zheza207). In this study, 82 top-canopy leaves of Zheza205 and 86 top-canopy leaves of Zheza207 were measured in visible-NIR reflectance mode. Discriminant models were developed using principal component analysis (PCA), discriminant analysis (DA), and discriminant partial least squares (DPLS) regression methods. After outliers detection, the samples were randomly split into two sets, one used as a calibration set (n=82) and the remaining samples as a validation set (n=82). When predicting the variety of the samples in validation set, the classification correctness of the DPLS model after optimizing spectral pretreatment was up to 93%. The DPLS model with raw spectra after multiplicative scatter correction and Savitzky-Golay filter smoothing pretreatments had the best satisfactory calibration and prediction abilities (correlation coefficient of calibration (R(c))=0.920, root mean square errors of calibration=0.196, and root mean square errors of prediction=0.216). The results show that visible-NIR spectroscopy might be a suitable alternative tool to discriminate tomato plant varieties on-site.
Design, Simulation and Fabrication of Electrowetting-Based Actuators for Integrated Digital Microfluidics (2006)

Electrowetting-on-dielectric (EWOD) is a promising method for manipulating tiny amounts of liquids. However, the miniaturization and the monolithic integration become the great challenges to improve the EWOD applications in actual lab-on-a-chip systems. In this paper, we present an IC-compatible digital microfluidic actuator, which uses silicon as the substrate and the thermally grown SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> film on heavily phosphorus-doped poly-silicon microelectrodes as the high quality dielectric layer. The fundamental EWOD operations, such as the droplet transportation, division, creation, and mergence, are numerically analyzed by using the computational fluidic software, CFD-ACE+. The simulation results of transportation and division show that it is an antinomy to select the gap height between two plates for improving respective performances. A tradeoff value of the gap height of 133 mum is ultimately used to implement the fundamental operations with one actuator. In experiments, all above operations are successfully achieved in air by applying 70 V voltages. Owing to the IC-compatible fabrication, the integration with peripheral circuits is technically feasible to achieve a miniaturized microfluidics
Mismatch amplification mutation assay (MAMA): application to the c-H-ras gene. (1992)

We have found that under appropriate conditions, an allele-specific polymerase chain reaction (PCR) can achieve a sensitivity suitable for measuring specific, infrequent mutations in single cell systems or in animal tissues. Using the 12th codon GC-to-AT mutation in the rat c-Ha-ras gene as a model system, we have defined conditions that allow for measurement of mutations present at frequencies as low as one in 10(5) gene copies. Our approach involved the use of PCR primers that created a single mismatch with the mutated allele (GAA) but created a double mismatch with the wild-type allele (GGA). Five out of the six such double-mismatch primers we tested permitted amplification of the mutant allele (GAA) with a high degree of specificity. The specificity of the assay was further enhanced by using a two-step PCR cycle consisting of a denaturation step (1 min incubation at 94 degrees C) and an annealing/extension step (1 min incubation at 50 degrees C) in the presence of 10% (vol/vol) glycerol. Reconstruction experiments using genomic DNA demonstrate that this procedure cna measure the presence of 30 copies of the transforming ras allele present amongst 3 x 10(6) copies of the wild-type allele.
Mycoplasma hyorhinis Activates the NLRP3 Inflammasome and Promotes Migration and Invasion of Gastric Cancer Cells (2013)

Our data suggest that activation of the NLRP3 inflammasome by M.hy may be associated with its promotion of gastric cancer metastasis, and anti-M.hy therapy or limiting NLRP3 signaling could be effective approach for control of gastric cancer progress.
Small Intestinal Submucosa as a Small-Diameter Arterial Graft in the Dog (1990)

Autogenous saphenous vein, human umbilical vein, modified bovine collagen, Dacron, and PTFE have been used as small-diameter arterial grafts with moderate success. We tested autogenous small intestine submucosa as a small-diameter arterial graft in both a carotid and femoral artery (mean ID 4.3 mm) of 18 dogs (total of 36 grafts). All dogs received aspirin and warfarin sodium for the first 8 weeks after surgery. Graft patency was evaluated by Doppler ultrasound techniques and angiography. Two grafts ruptured and 5 grafts occluded by 21 days after surgery. One graft became occluded at 14 weeks. Fifteen dogs were sacrificed at periodic intervals until 48 weeks after surgery. Patent grafts had no evidence of infection, propagating thrombus, or intimal hyperplasia. Graft aneurysmal dilation occurred in 4 grafts (11%). The grafts were composed of a dense organized collagenous connective tissue with no evidence of endothelial cell growth on the smooth luminal surface. Three dogs are alive at 76 to 82 weeks after surgery. Overall, graft patency was 75%. Graft patency after cessation of anticoagulation therapy was 92.3% (12 of 13 grafts). We conclude that autogenous small intestinal submucosa can be used as a small-diameter arterial graft in the dog and is worthy of further investigation.
Solar Power Beaming: From Space to Earth (2009)

Harvesting solar energy in space and power beaming the collected energy to a receiver station on Earth is a very attractive way to help solve mankind's current energy and environmental problems. However, the colossal and expensive 'first step' required in achieving this goal has to-date stifled its initiation. In this paper, we will demonstrate that recent advance advances in laser and optical technology now make it possible to deploy a space-based system capable of delivering 1 MW of energy to a terrestrial receiver station, via a single unmanned commercial launch into Low Earth Orbit (LEO). Figure 1 depicts the overall concept of our solar power beaming system, showing a large solar collector in space, beaming a coherent laser beam to a receiving station on Earth. We will describe all major subsystems and provide technical and economic discussion to support our conclusions.
Diagnosis and prognosis of congenital CMV infection: A case report and review of the literature (2014)

Congenital cytomegalovirus (CMV) infection is the leading non-genetic cause of sensori-neural hearing loss and neurodevelopmental sequelae. Despite these alarming facts, the general public healthcare system is often not aware of CMV and not enough is done to prevent congenital CMV infection.We describe the clinical and laboratory monitoring of a case with primary CMV infection occurring before the first trimester of gestation. Specific literature review is included in order to point out major goals achieved in the diagnosis and prognosis of congenital CMV infection and the many questions still unanswered. Serological diagnosis of primary CMV infection was performed based on serum-CMV specific-IgM antibodies, combined with low avidity anti-CMV IgG antibodies. The maternal infection was asymptomatic, as it is for most infections in immunocompetent patients. Therefore, disclosing primary infection depended on specific serological tests during the initial period of pregnancy (before weeks 12-16 of gestation). The invasive (amniocentesis) and non-invasive (ultrasonographic examination) prenatal tests, carried out at 21 weeks gestation, revealed a severe CMV infection in a fetus small for gestational age with ventriculomegaly. The presence of overt ultrasound abnormalities combined with high viral load in the amniotic fluid sampled at the appropriate times was highly suggestive of an unfavourable prognosis. The autopsy performed on the fetus confirmed severe disseminated CMV infection with histological brain damage.
Frameshift mutations in rdxA and metronidazole resistance in North American Helicobacter pylori isolates (2000)

In Helicobacter pylori, the oxygen-insensitive nitroreductase RdxA is likely to activate metronidazole (Mtz) by reduction and formation of cytotoxic intermediates. Mutations in rdxA have been associated with Mtz resistance in H. pylori. In vitro Mtz susceptibilities of 17 randomly selected H. pylori isolates were determined by the agar dilution method. DNA sequence analysis of rdxA alleles of eight susceptible isolates (MIC range: 0.25-1.0 mg/L) and nine resistant isolates (MIC range: 16-256 mg/L) showed that six of nine Mtz-resistant H. pylori isolates contained insertion or deletion mutations ('indel' mutations). One isolate contained a substitution mutation at codon position 148 that resulted in the introduction of a premature stop codon. Creation of stop codons within the rdxA coding sequence by either frameshift or substitution mutations resulted in premature translation termination and expression of putatively truncated RdxA polypeptides.
Induction and suppression of immunoglobulin synthesis in cultures of human lymphocytes: effects of pokeweed mitogen and Staphylococcus aureus Cowan I. (1980)

The synthesis and secretion of immunoglobulins by human peripheral blood mononuclear cells in cultures stimulated with pokeweed mitogen or Staphylococcus aureus Cowan I were evaluated by enumeration of cells containing cytoplasmic immunoglobulins and cells actively secreting immunoglobulins, and by quantitation of immunoglobulins released into culture supernatants. The two mitogens caused comparable stimulation of immunoglobulin production; however, in contrast to pokeweed mitogen, S. aureus was active in cultures depleted of T lymphocytes, and its stimulatory effects were resistant to the influence of suppressor T cells generated by co-stimulation with concanavalin A or by preincubation without mitogenic stimulus. These results indicate distinct pathways of induction and suppression of immunoglobulin synthesis for these two polyclonal B cell activators, and suggest that stimulation by S. aureus is less thymus dependent than that induced by pokeweed mitogen.
Inhibition of p34cdc2 kinase activity by etoposide or irradiation as a mechanism of G2 arrest in Chinese hamster ovary cells. (1990)

The mammalian homologue of the yeast cdc2 gene product, p34cdc2, is a cell cycle-regulated protein essential for mitosis. We have used polyclonal antisera raised against a peptide corresponding to the carboxyl terminus of the sequence of human cdc2 to study p34cdc2 in Chinese hamster ovary (CHO) cells. Major bands are immunoprecipitated at a molecular weight of 34,000, although not in the presence of competing antigenic peptide. p34cdc2 is coimmunoprecipitated with proteins of molecular weights of 52,000 and 57,000. Immunoprecipitates express histone H1 kinase activity which varies throughout the cell cycle, maximal activity being observed in G2-M. The activity of the p34cdc2 kinase varies according to its association with the Mr 52,000 and 57,000 proteins and according to their phosphorylation state. Treatment of either asynchronous CHO cells or an enriched G2 population with the antitumor agent, etoposide, results in rapid inhibition of immunoprecipitated p34cdc2 kinase activity, which is not due to a direct effect of drug upon the enzyme. p34cdc2 kinase activity recovers as cells arrest in G2 and a second etoposide treatment further inhibits p34cdc2 kinase activity and prolongs G2 arrest. Exposure of asynchronous CHO cells to gamma-irradiation also inhibits p34cdc2 kinase activity within 1 h. Again this activity recovers as cells accumulate in G2. These results suggest that DNA damage in CHO cells elicits a response which results in inhibition of p34cdc2 kinase activity and, consequently, G2 arrest.
Cure of SCID mice bearing human B-lymphoma xenografts by an anti-CD74 antibody-anthracycline drug conjugate. (2003)

CD74 appears to be a uniquely useful target antigen for delivery of drugs, effecting cures of animals with single, low doses of conjugate.