gebhart/patrepeval huggingface dataset:
Without nerves, immunology remains incomplete –<i>in vivo veritas</i> (2005)

Interest in the interactions between nervous and immune systems involved in both pathological and homeostatic mechanisms of host defence has prompted studies of neuroendocrine immune modulation and cytokine involvement in neuropathologies. In this review we concentrate on a distinct area of homeostatic control of both normal and abnormal host defence activity involving the network of peripheral c-fibre nerve fibres. These nerve fibres have long been recognized by dermatologists and gastroenterologists as key players in abnormal inflammatory processes, such as dermatitis and eczema. However, the involvement of nerves can all too easily be regarded as that of isolated elements in a local phenomenon. On the contrary, it is becoming increasingly clear that neural monitoring of host defence activities takes place, and that involvement of central/spinal mechanisms are crucial in the co-ordination of the adaptive response to host challenge. We describe studies demonstrating neural control of host defence and use the specific examples of bone marrow haemopoiesis and contact sensitivity to highlight the role of direct nerve fibre connections in these activities. We propose a host monitoring system that requires interaction between specialized immune cells and nerve fibres distributed throughout the body and that gives rise to both neural and immune memories of prior challenge. While immunological mechanisms alone may be sufficient for local responsiveness to subsequent challenge, data are discussed that implicate the neural memory in co-ordination of host defence across the body, at distinct sites not served by the same nerve fibres, consistent with central nervous mediation.
Hierarchical assembly of a self-replicating spacecraft (2017)

Extraterrestrial fabrication of spacecraft by current best-practice manufacturing methods is complicated by the need to integrate thousands of unique parts, each made using a diversity of processes and raw materials. Reducing this complexity could enable exponential space exploration via self-replicating spacecraft (known as Von Neumann probes). We propose a hierarchical model for machine design, based on 13 reversibly-assembled part types, reducing the complexity of machine self-replication and bridging prior work in the areas of in-situ resource utilization (ISRU) and modular robotics. Analogous to amino acids in biological systems, these parts form a basis set for the electronic and mechanical subsystems of an exploratory spacecraft. In simulation we validate representative subsystem designs and develop a hierarchical architecture for the design of mechanisms, actuation, and electronics. By standardizing and modularizing the parts, we drastically reduce the diversity of the required supply chain as well as the minimum viable payload mass. We estimate that a seed launch could contain approximately 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup> parts, fit within the envelope of a 3U cubesat, and enable the assembly of over one hundred self-replicating assemblers.
Expression of Hepatitis C Virus Ns5a Natural Mutants in A Hepatocytic Cell Line Inhibits the Antiviral Effect of Interferon in A Pkr–Independent Manner (2001)

The impact of hepatitis C virus NS5A protein mutations on interferon alfa (IFN-alpha) signaling pathway, cell proliferation, and viability is an important issue that is still under debate. We have therefore combined transient and stable expression in a human hepatocytic cell line (Huh7) of 3 full-length NS5A sequences, isolated from patients with or without response to IFN-alpha therapy. Expression of all 3 NS5A-reduced IFN-alpha global antiviral activity on both vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV) replication. We did not show, however, an effect of these 3 NS5A proteins on double-stranded RNA-dependent kinase (PKR) expression and activity as well as colocalization and coimmunoprecipitation between NS5A and PKR. We also failed to show an effect of the 3 NS5A mutants tested on cell proliferation and viability. Overall, our results support an important role of NS5A in controlling IFN-alpha antiviral activity; they show, however, that PKR-independent mechanisms are implicated, at least in liver-derived cells.
Profound contribution of a carboxymethyl group to transition-state stabilization by cytidine deaminase: Mutation and rescue (1995)

The crystal structure of an inhibitory complex formed between Escherichia coli cytidine deaminase and the transition-state analog 3,4-dihydrouridine indicates the presence of a short H-bond between Glu-104 and the inhibitor. To test the possibility that analogous H-bonds might play a significant role in stabilizing the hydrated substrate in the transition state for deamination, we replaced Glu-104 by alanine. Compared with the wild-type enzyme, the mutant enzyme's affinities for substrate cytidine and product uridine were found to have increased, whereas kcat for deamination of cytidine had been reduced by 8 orders of magnitude. By its presence, the carboxymethyl group of Glu-104 appears to minimize the activation barrier for deamination, not only by stabilizing the altered substrate in the transition state but also by destabilizing the enzyme-substrate and enzyme-product complexes. In the presence of added formate ion, but not in the presence of bulkier carboxylic acids, the low catalytic activity of the mutant enzyme was enhanced substantially.
The Drosophila homologue of the 64 kDa subunit of cleavage stimulation factor interacts with the 77 kDa subunit encoded by the suppressor of forked gene (2000)

During mRNA 3' end formation, cleavage stimulation factor (CstF) binds to a GU-rich sequence downstream from the polyadenylation site and helps to stabilise the binding of cleavage-polyadenylation specificity factor (CPSF) to the upstream poly-adenylation sequence (AAUAAA). The 64 kDa subunit of CstF (CstF-64) contains an RNA binding domain and is responsible for the RNA binding activity of CstF. It interacts with CstF-77, which in turn interacts with CPSF. The Drosophila suppressor of forked gene encodes a homologue of CstF-77, and mutations in it affect mRNA 3' end formation in vivo. A Drosophila homologue for CstF-64 has now been isolated, both through homology with the human protein and through protein-protein interaction in yeast with the suppressor of forked gene product. Alignment of CstF-64 homologues shows that the proteins have a conserved N-terminal 200 amino acids, the first half of which is the RNA binding domain with the second half likely to contain the CstF-77 interaction domain; a central region variable in length and rich in glycine, proline and glutamine residues and containing an unusual degenerate repeat motif; and then a conserved C-terminal 50 amino acids. In Drosophila, the CstF-64 gene has a single 63 bp intron, is transcribed throughout development and probably corresponds to l(3)91Cd.
A Novel V/f Scalar Controlled Induction Motor Drives with Compensation Based on Decoupled Stator Current (2006)

A novel open-loop scalar control method for induction motor that provides desirable operation in low frequency is presented. The control scheme is based on the popular constant volts per hertz (V/F) only using the current sensors. Based on the mathematical model of the induction motor, the rotor flux vector is estimated to decouple the stator current. The slip frequency and the current-resistant (IR) stator voltage drop are estimated and compensated based on flux and torque component of the stator current in the rotor-flux oriented reference frame. It shows that, by using the proposed method, the speed can be controlled down to 1Hz with full load torques.
Improvement of performance of EIGRP network by using a supervisory controller with smart congestion avoidance algorithm (2016)

The aim of this research is to enhance the performance of a traditional Enhanced Interior Gateway Routing Protocol (EIGRP) network by adding some features of the Software Defined Networking (SDN) in a modified approach to improve some network's performance metrics like link congestion and packet loss. The improvement of those metrics leads to an improvement in the total throughput of the network. This approach results in a network that contains an intelligent dynamic supervisory corrector controller, which is capable of detecting the location of a congestion that may take place before or at the brink of its occurrence and dealing with selected flows on selected routers across the network in a way that prevents the congestion by using a smart heuristic congestion avoidance and routing algorithm thereby reducing the generation of control messages as much as possible.
Mutational analysis of splicing machinery genes <scp><i>SF3B1, U2AF1</i></scp> and <scp><i>SRSF2</i></scp> in myelodysplasia and other common tumors (2013)

Recurrent somatic mutations in splicing machinery components, including SF3B1, U2AF1 and SRSF2 genes have recently been reported in myelodysplastic syndromes (MDS). Such a recurrent nature strongly suggests that these mutations play important roles in tumor development. To see whether SF3B1, U2AF1 and SRSF2 mutations occur in other human tumors besides MDS, we analyzed the hotspot mutation regions of these genes in 2,345 tumor tissues from various origins (61 MDS, other 616 hematologic tumors, 1,421 epithelial tumors and 247 non-epithelial stromal tumors) by single-strand conformation polymorphism analysis. We found SF3B1, U2AF1 and SRSF2 mutations in 5 (8.2%), 12 (19.7%) and 8 (13.1%) of 61 MDS, respectively. We also confirmed these mutations in other myeloid neoplasia, including de novo acute myelogenous leukemia (AML), chronic myelomonocytic leukemia and MDS/myeloproliferative disorder. In addition, we discovered that the SRSF2 gene was mutated in two childhood acute lymphoblastic leukemias (childhood ALL) (1.5%). In solid tumors, we found SF3B1 mutations in gastric and prostate cancers, and U2AF1 mutation in a borderline mucinous tumor of ovary, but the overall incidences of the hotspot mutation regions were very low (0.2%). Our data suggest that SF3B1, U2AF1 and SRSF2 mutations occur not only in myeloid lineage tumors but also in lymphoid lineage tumors. The data suggest that the splicing gene mutations play important roles in the pathogenesis of hematologic tumors, but rarely in solid tumors.
Reinforcing Material Lay-Up Quality Control (2001)

Abstract In-process inspection during composite material lay-up is essential if the structural, dimensional, and environmental performance designed into a part is to be consistently achieved. This article discusses the requirements to be met by the facilities and equipment to produce high-quality composites. It reviews the procedures that are allowed and prohibited in controlled-contamination areas of lay-up. The article emphasizes significant areas, such as material control and lay-up process, in which quality-control personnel can be effective in preventing production problems. It concludes with a discussion on automated tape laying and fiber placement, as well as the numerically aided lay-up process.
Taxol induces the assembly of free microtubules in living cells and blocks the organizing capacity of the centrosomes and kinetochores. (1981)

Taxol, a potent promoter of microtubule polymerization in vitro, induces massive assembly of free microtubules in cultured cells as visualized by immunocytochemistry and electron microscopy. The centrosomes and kinetochores largely lost their capacity to organize microtubule assembly, as became evident by the disappearance of the cytoplasmic microtubule complex and the mitotic spindle. The taxol-induced microtubules were partially resistant to nocodazole, an inhibitor of tubulin polymerization. Moreover, taxol induced microtubule assembly in cells pretreated with nocodazole. Increasing the ratio of nocodazole to taxol restored the ability of the centrosomes and kinetochores to specifically induce microtubule assembly in their immediate vicinity. The data suggest that taxol lowers the critical tubulin concentration in vivo as well as in vitro and that the organizing capacity of the microtubule-organizing centers depends on the cytoplasmic polymerization threshold.
Tamoxifen Isomers and Metabolites Exhibit Distinct Affinity and Activity at Cannabinoid Receptors: Potential Scaffold for Drug Development (2016)

Tamoxifen (Tam) is a selective estrogen receptor (ER) modulator (SERM) that is an essential drug to treat ER-positive breast cancer. Aside from known actions at ERs, recent studies have suggested that some SERMs like Tam also exhibit novel activity at cannabinoid subtype 1 and 2 receptors (CB1R and CB2Rs). Interestingly, cis- (E-Tam) and trans- (Z-Tam) isomers of Tam exhibit over a 100-fold difference in affinity for ERs. Therefore, the current study assessed individual isomers of Tam and subsequent cytochrome P450 metabolic products, 4-hydroxytamoxifen (4OHT) and 4-hydroxy-N-desmethyl tamoxifen (End) for affinity and activity at CBRs. Results showed that Z-4OHT, but not Z-Tam or Z-End, exhibits higher affinity for both CB1 and CB2Rs relative to the E-isomer. Furthermore, Z- and E-isomers of Tam and 4OHT show slightly higher affinity for CB2Rs, while both End isomers are relatively CB1R-selective. When functional activity was assessed by G-protein activation and regulation of the downstream effector adenylyl cyclase, all isomers examined act as full CB1 and CB2R inverse agonists. Interestingly, Z-Tam appears to be more efficacious than the full inverse agonist AM630 at CB2Rs, while both Z-Tam and Z-End exhibit characteristics of insurmountable antagonism at CB1 and CB2Rs, respectively. Collectively, these results suggest that the SERMs Tam, 4OHT and End elicit ER-independent actions via CBRs in an isomer-specific manner. As such, this novel structural scaffold might be used to develop therapeutically useful drugs for treatment of a variety of diseases mediated via CBRs.
Catalytic Hydrogenation of Solvent-Refined Lignite to Liquid Fuels (1976)

Abstract Solvent-refined lignite (SRL) can be produced by treating lignite (not dried) with CO-H2, donor solvent and high temperature. This reactive black solid softens at about 150°C, is soluble in many organic solvents, is very low in ash and sulfur, and appears to be a good feedstock for further upgrading. Thus a wide-ranging study was undertaken to determine the best reducing conditions for converting SRL to light distillable liquid fuels and/or chemical feedstocks. Batch autoclave studies were carried out in the temperature range of 375-450°C, hydrogen pressure range of 1500-4500 psi, with catalysts Ni-Mo-Al2O3, Co-Mo-Al2O3, Ni-W-Al2O3, Ni-W-SiO2-Al2O3, SiO2-Al2O3, Al2 O3, SnCl2, and presulfided catalysts Ni-Mo-Al2O3, Co-Mo-Al2O3, NiW-Al2O3. Varying amounts of the solvents tetrahydrofuran, tetralin, nap-thalene, and FS-120 petroleum fraction were also studied. Reductions without any solvent were studied too and were quite successful. The results were evaluated in terms of the amount of light liquids produced [Table 3 distillation fractions (1) initial boiling point to 89°C/1 torr, (2) 89-139°C, (3) 139-200°C, (4) 200-260°C, (5) above 260°C], deoxygenation, denitrification, hydrogen-carbon ratios, aromatic-aliphatic hydrogen ratios, and benzene solubility of unconverted material. Best results were obtained with a presulfided Ni-Mo-Al2O3 catalyst at 450°C, operating pressure of about 3500 psi with a 1:1 SRL-tetralin solvent ratio [90% overall conversion, ∼ 20% light liquid (1), 15% light oil (2), 20% heavy oil (3 and 4), 10% unconverted].
Isolation and characterization of the gene encoding a novel, thermostable serine proteinase from the mould <i>Tritirachium album</i> Limber (1990)

A number of proteinases are induced and secreted into the culture medium of Tritirachium album Limber when the nitrogen source is limited to exogenous proteins. We have constructed a cDNA library using the polyadenylated RNA isolated during the nutritional induction with bovine serum albumin. A full-length clone of a gene for a new proteinase (named proteinase R) was identified from this library. This clone contained sequences coding for the 108-amino-acid prepro-leader as well as for the 279-amino-acid mature proteinase. Proteinase R apparently belongs to the subtilisin group of serine proteases that contains disulphide bonds. Homology between proteinase R and proteinase K was found to be about 87% at the nucleotide as well as at the amino acid level. The Brookhaven Protein Data Base co-ordinate file of proteinase K was used as a template to study the proteinase R substitutions in three-dimensional space. The majority of the substitutions of proteinase R with respect to proteinase K were found to be on the exterior of the protein model.
“Polaroid” (1937)

<div class="htmlview paragraph"><b>THE perfect, hypothetical headlight is visualized, and a set of standards formulated that makes night driving as safe as day driving, with the illumination invisible to approaching cars.</b></div> <div class="htmlview paragraph"><b>Theory of glare elimination with polarized light is presented. The nature of “Polaroid” and how it solves the problem is pointed out.</b></div> <div class="htmlview paragraph"><b>The new engineering and lighting problems, which the use of this material involves, are discussed.</b></div> <div class="htmlview paragraph"><b>Examples of the use of the new control of light for industry are related.</b></div>
Automated Finite Element Model Mesh Updating Scheme Applicable to Mistuning Analysis (2014)

Advancement of optical geometric measurement hardware has enabled the construction of accurate 3D tessellated models for a wide range of turbomachinery components. These tessellated models can be reverse-engineered into computer-aided design (CAD) models and input into grid generation software for finite element analyses. However, generating a CAD model from scan data is a time consuming and cumbersome process requiring significant user-involvement for even a single model. While it is possible to generate finite element models (FEMs) directly from tessellated data, current direct-grid methods produce unstructured grids that can introduce fictitious, numerical mistuning in these models, obscuring geometric mistuning. Nonetheless, as-measured scan data captured in a structured grid is essential for accurate geometric mistuning analyses, provided the tessellated scan data can be rapidly and accurately transformed into a FEM. This paper outlines and demonstrates an approach for rapidly generating structured FEMs for a population of integrally bladed rotors (IBRs) without requiring the arduous task of generating a CAD model for each as-measured IBR. This is accomplished by morphing the structured mesh of a nominal model to the tessellated data set collected from an optical scanner. It is shown that the fidelity and structure of these FEMs can be utilized for accurate mistuning analyses.
Beam-orientation customization using an artificial neural network (1999)

A methodology for the constrained customization of coplanar beam orientations in radiotherapy treatment planning using an artificial neural network (ANN) has been developed. The geometry of the patients, with cancer of the prostate, was modelled by reducing the external contour, planning target volume (PTV) and organs at risk (OARs) to a set of cuboids. The coordinates and size of the cuboids were given to the ANN as inputs. A previously developed beam-orientation constrained-customization (BOCC) scheme employing a conventional computer algorithm was used to determine the customized beam orientations in a training set containing 45 patient datasets. Twelve patient datasets not involved in the training of the artificial neural network were used to test whether the ANN was able to map the inputs to customized beam orientations. Improvements from the customized beam orientations were compared with standard treatment plans with fixed gantry angles and plans produced from the BOCC scheme. The ANN produced customized beam orientations within 5 degrees of the BOCC scheme in 62.5% of cases. The average difference in the beam orientations produced by the ANN and the BOCC scheme was 7.7 degrees (+/-1.7, 1 SD). Compared with the standard treatment plans, the BOCC scheme produced plans with an increase in the average tumour control probability (TCP) of 5.7% (+/-1.4, 1 SD) whilst the ANN generated plans increased the average TCP by 3.9% (+/-1.3, 1 SD). Both figures refer to the TCP at a fixed rectal normal tissue complication probability (NTCP) of 1%. In conclusion, even using a very simple model for the geometry of the patient, an ANN was able to produce beam orientations that were similar to those produced by a conventional computer algorithm.
Protein Kinase C Recognizes the Protein Kinase A-binding Motif of Nonstructural Protein 3 of Hepatitis C Virus (1999)

The nonstructural protein 3 (NS3) of hepatitis C virus (HCV) inhibits the nuclear transport and the enzymatic activity of the catalytic subunit of protein kinase A. This inhibition is mediated by an arginine-rich domain localized between amino acids 1487-1500 of the HCV polyprotein. The data presented here indicate that the arginine-rich domain, when embedded in recombinant fragments of NS3, interacts with the catalytic site of protein kinase C (PKC) and inhibits the phosphorylation mediated by this enzyme in vitro and in vivo. Furthermore, a direct binding of PKC to the NS3 fragments leads to an inhibition of the free shuttling of the kinase between the cytoplasm and the particulate fraction. In contrast, a peptide corresponding to the arginine-rich domain (HCV (1487-1500)), despite also being a PKC inhibitor, did not influence the PKC shuttling process and was transported to the particulate fraction by the translocating kinase upon activation with tetradecanoylphorbol-13-acetate. Using the tetradecanoylphorbol-13-acetate -stimulated respiratory burst of NS3-introduced neutrophils as a model system, we could demonstrate that NS3 is able to block PKC-mediated functions within intact cells. Our data support the possibility that NS3 disrupts the PKC-mediated signal transduction.
Dead Weight Piston Gauge for Pressures to 26 Kilobars (1967)

The design and operation of a dead weight piston gauge for pressures to 26 kilobars is described. The gauge is of the controlled clearance type. The diameter of the gauge piston is 0.2 cm. It is loaded directly with up to 840 kg of weights. A volume of about 1 cm3 is provided inside the gauge for the material under test. The use of this gauge for transition pressure determinations is briefly discussed.
Heritability, Linkage, and Genetic Associations of Exercise Treadmill Test Responses (2007)

Hemodynamic and chronotropic responses to exercise are heritable and demonstrate suggestive linkage to select loci. Genetic mapping with newer approaches such as genome-wide association may yield novel insights into the physiological responses to exercise.
A single event transient hardening circuit design technique based on strengthening (2013)

In a near future of high-density and low-power technologies, the study of soft errors will not only be relevant for memory systems and latches of logic circuits, but also for the combinational parts of logic circuits which seriously affect the system's operation. In this paper, we present a novel design strategy to reduce the impact of radiation-induced single event transients (SET) on logic circuits. This design style achieves SET mitigation by Strengthening the sensitive node using a likeness to feedback techniques. We have analyzed several techniques from hardening radiation at transistor level to a single event transient in 7nm FinFET devices. Simulation results have shown the proposed method has higher soft error robustness than the existing ones.