gebhart/patrepeval huggingface dataset:
Drilling a 2-inch in Diameter Hole in Granites Submerged in Water by CO2 Lasers (2009)

Abstract As part of a fundamental study of rock drilling by laser irradiation, this paper describes laser drilling of a 2-inch-in-diameter hole in granites submerged in water. In the air, fused rock produced by laser irradiation reflects or absorbs successively irradiated laser beams, thereby refraining laser heat from being transmitted into the rock. This absorption leads both to a temperature rise of the fused rock and a further increase in absorption of laser radiation by the fused rock, causing the rock destruction process to cease completely. From consideration of the lack of success in past laser rock drilling methods, we arrived at the idea that laser-induced mechanical forces could be utilized to generate a hole in rocks by laser irradiation in water. A granite specimen was submerged at 50mm from a water-surface and then 10.6 pm carbon dioxide laser (CO2) beams which have a high absorption coefficient in water were intermittently irradiated. The laser beams induced underwater shock waves, bubble formations, and micro-water jet formations upon bubble collapse. High-speed video observations revealed the generation of an initial cone-shaped cavity in the water, propagation of the laser beams through the cavity and eventual ablation of the granite surface. The laser beams locally melt the granite surface to form small glassy beads, which are readily removable by mechanical methods. Repetition of this procedure demonstrated that a high-power laser beam propagating in water can be used to generate a hole in rocks. The laser beam irradiation indeed drilled the granite specimen submerged in the water. A 2-inch-in-diameter hole in the underwater granites was successfully generated by two methods that were melting and spalling by the laser. Melting the granite to generate a 2-inch-in-diameter hole requires energy almost 3 times as much as spalling the granite to generate the same size hole.
Studies on prolysostaphin processing and characterization of the lysostaphin immunity factor (Lif) of Staphylococcus simulans biovar staphylolyticus (1997)

Lysostaphin is an extracellular glycylglycine endopeptidase produced by Staphylococcus simulans biovar staphylolyticus ATCC1362 that lyses staphylococcal cells by hydrolysing the polyglycine interpeptide bridges of the peptidoglycan. Renewed analysis of the sequence of the lysostaphin gene (lss), and the sequencing of the amino-terminus of purified prolysostaphin and of mature lysostaphin revealed that lysostaphin is organized as a preproprotein of 493 amino acids (aa), with a signal peptide consisting of 36 aa, a propeptide of 211 aa from which 195 aa are organized in 15 tandem repeats of 13 aa length, and a mature protein of 246 aa. Prolysostaphin is processed in the culture supernatant of S. simulans biovar staphylolyticus by an extracellular cysteine protease. Although prolysostaphin was staphylolytically active, the mature lysostaphin was about 4.5-fold more active. The controlled expression in Staphylococcus carnosus of lss and lss with deletions in the prepropeptide region indicated that the tandem repeats of the propeptide are not necessary for protein export or activation of Lss, but keep Lss in a less active state. Intracellularly expressed pro- and mature lysostaphin exert staphylolytic activity in cell-free extracts, but do not affect growth of the corresponding clones. We characterized a lysostaphin immunity factor gene (lif) which is located in the opposite direction to lss. The expression of lif in S. carnosus led to an increase in the serine/glycine ratio of the interpeptide bridges of peptidoglycan from 2 to 35%, suggesting that lysostaphin immunity depends on serine incorporation into the interpeptide bridge. If, in addition to lif, lss is co-expressed the serine/glycine ratio is further increased to 58%, suggesting that Lss selects for optimal serine incorporation. Lif shows similarity to FemA and FemB proteins, which are involved in the biosynthesis of the glycine interpeptide bridge of staphylococcal peptidoglycan. In contrast to that of Lif, the production of FemA and FemB in S. carnosus does not cause lysostaphin immunity. The putative tRNASer gene located downstream of lss had no recognizable influence on lysostaphin immunity. lss and lif are flanked by insertion sequences, suggesting that S. simulans biovar staphylolyticus received lif and lss by horizontal gene transfer.
Oxidation Regulates the Inflammatory Properties of the Murine S100 Protein S100A8 (1999)

The myeloid cell-derived calcium-binding murine protein, S100A8, is secreted to act as a chemotactic factor at picomolar concentrations, stimulating recruitment of myeloid cells to inflammatory sites. S100A8 may be exposed to oxygen metabolites, particularly hypochlorite, the major oxidant generated by activated neutrophils at inflammatory sites. Here we show that hypochlorite oxidizes the single Cys residue (Cys41) of S100A8. Electrospray mass spectrometry and SDS-polyacrylamide gel electrophoresis analysis indicated that low concentrations of hypochlorite (40 microM) converted 70-80% of S100A8 to the disulfide-linked homodimer. The mass was 20,707 Da, 92 Da more than expected, indicating additional oxidation of susceptible amino acids (possibly methionine). Phorbol 12-myristate 13-acetate activation of differentiated HL-60 granulocytic cells generated an oxidative burst that was sufficient to efficiently oxidize exogenous S100A8 within 10 min, and results implicate involvement of the myeloperoxidase system. Moreover, disulfide-linked dimer was identified in lung lavage fluid of mice with endotoxin-induced pulmonary injury. S100A8 dimer was inactive in chemotaxis and failed to recruit leukocytes in vivo. Positive chemotactic activity of recombinant Ala41S100A8 indicated that Cys41 was not essential for function and suggested that covalent dimerization may structurally modify accessibility of the chemotactic hinge domain. Disulfide-dependent dimerization may be a physiologically significant regulatory mechanism controlling S100A8-provoked leukocyte recruitment.
Macroscopically distinct quantum-superposition states as a bosonic code for amplitude damping (1999)

We show how macroscopically distinct quantum superposition states (Schr\"odinger cat states) may be used as logical qubit encodings for the correction of spontaneous emission errors. Spontaneous emission causes a bit flip error, which is easily corrected by a standard error correction circuit. The method works arbitrarily well as the distance between the amplitudes of the superposed coherent states increases.
Demonstration of a Novel Gene DEXT3 ofDrosophila melanogaster as the EssentialN-Acetylglucosamine Transferase in the Heparan Sulfate Biosynthesis (2002)

Hereditary multiple exostoses gene (EXT) family members encode glycosyltransferases required for heparan sulfate (HS) biosynthesis in humans as well as in Drosophila. In the present study, we identified a novel Drosophila EXT protein with a type II transmembrane topology and demonstrated its glycosyltransferase activities. The truncated soluble form of this new homolog designated DEXT3 transferred N-acetylglucosamine (GlcNAc) through an alpha1,4-linkage not only to N-acetylheparosan oligosaccharides that represent growing HS chains (alpha-GlcNAc transferase II activity) but also to GlcUAbeta1-3Galbeta1-O-C(2)H(4)NHCbz, a synthetic substrate for alpha-GlcNAc transferase I that determines and initiates HS biosynthesis. The results suggest that DEXT3 is the ortholog of human EXTL3 and Caenorhabditis elegans rib-2. Semiquantitative reverse transcriptase-PCR analysis revealed ubiquitous expression of the DEXT3 mRNA. Based on the findings of the present study and those of a recent study where a fly mutant, deficient in the botv gene identical to DEXT3, affected HS proteoglycan-mediated developmental signalings, it is suggested that DEXT3 with the revealed glycosyltransferase activities is critically involved in HS formation in Drosophila. These results suggest the essential roles of DEXT3, its human ortholog EXTL3, and the C. elegans ortholog rib-2 in the biosynthesis of heparan sulfate and heparin, if present, in the respective organisms.
Response of Atrial Fibrillatory Activity to Carotid Sinus Massage in Patients with Atrial Fibrillation (2001)

In some cases carotid sinus massage (CSM) may induce AF, whereas it may terminate AF in others. The purpose of this study was to investigate the influence of CSM on atrial fibrillatory frequency using spectral analysis of the surface ECG. Continuous ECG recordings were made in 19 patients (12 men, 7 women, mean age 61 +/- 11 years) with AF. Unilateral CSM was performed in the standard fashion to one randomized bifurcation of the carotid artery at a time. Ventricular rate and fibrillatory frequency were assessed in 30-second ECG segments at baseline and during CSM. The frequency content of the fibrillatory baseline was quantified using digital signal processing (filtering, subtraction of averaged QRST complexes, and Fourier transformation). CSM resulted in a relative change in fibrillatory frequency of 4.5 +/- 3.9% (range 0%-13%). In 8 (42%) patients an increase in fibrillatory frequency was found (6.4 +/- 0.5 vs 6.8 +/- 0.5 Hz, P = 0.012). In 9 (47%) patients a decrease in fibrillatory frequency occurred (6.5 +/- 0.8 vs 6.1 +/- 0.8 Hz, P = 0.008) without AF termination. The remaining two patients showed no change in fibrillatory frequency. CSM on the contralateral side after 2 minutes produced fibrillatory frequency changes in the same direction in all patients with a good reproducibility in its magnitude (r = 0.59, P = 0.05). Calcium channel blockers were more frequently used (78% vs 25%, P = 0.044) in patients with a decrease in fibrillatory frequency compared to patients with a frequency increase. There were no significant changes in ventricular rate during CSM. In conclusion, two different responses of atrial fibrillatory frequency to CSM were found. This might explain why CSM may facilitate AF induction in some cases and AF termination in others. Calcium channel blocker treatment may prevent an increase in fibrillatory frequency provoked by CSM suggesting a blunted electrical remodeling process.
Dynamic Atomic-Level Rearrangements in Small Gold Particles (1986)

Small metal particles (<5 nanometers), which are widely used in catalysis, have physical and chemical properties that are markedly different from those of the bulk metal. The differences are related to crystal structure, and it is therefore significant that structral rearrangements in small particles have been observed in real time by using high-resolution electron microscopy. A detailed investigation at the atomic level has been made of the factors affecting the dynamic activity of small gold crystals that are supported on thin films of amorphous carbon, silicon, and germanium. The rate of activity depends mainly on the current density of the incident electron beam and the degree of contact of the particle with the substrate, but this rate decreases rapidly as the particle size is increased. The activity of the particles is very similar on either carbon or silicon, but it is generally less marked on germanium because of increased contact between the particle and the substrate. The electron beam effectively heats the particles, and it appears that their dynamic behavior depends on their thermal contact with the substrate.
Elevation of the level and activity of acid ceramidase in Alzheimer's disease brain (2004)

Protein glycosylation modifies the processing of several key proteins involved in the molecular pathogenesis of Alzheimer's disease (AD). Aberrant glycosylation of tau and down-regulation of sialyltransferase in AD brain suggest a possible dysregulation of protein glycosylation that may play a role in AD. We therefore isolated major glycoproteins from AD brain by using lectin-affinity chromatographies and ion-exchange chromatography and further separated them using SDS-polyacylamide gel electrophoresis. Mass spectrometry analysis of 11 isolated glycoproteins led to their identification as: neuronal cell adhesion molecule, beta-globin, IgM heavy chain VH1 region precursor, contactin precursor, dipeptidylpeptidase VI, CD81 partner 3, prenylcysteine lyase, adipocyte plasma-associated protein, acid ceramidase and two novel proteins. We found that the level and activity of acid ceramidase (AC), one of the major identified human brain glycoproteins, were significantly elevated in AD brain. Immunohistochemical staining indicated that AC was located mainly in the cell bodies of neurons and colocalized with neurofibrillary tangles. Our findings suggest that AC might play a role in controlling neuronal apoptosis and that AC-mediated signalling pathways might be involved in the molecular mechanism of AD.
Formulation and stability of freeze-dried proteins: effects of moisture and oxygen on the stability of freeze-dried formulations of human growth hormone. (1992)

This research presents the results of a series of stability studies on freeze-dried formulations of human growth hormone (hGH). Chemical decomposition via methionine oxidation and asparagine deamidation as well as irreversible aggregation are characterized by HPLC. Water sorption isotherms, DSC thermograms, and pulsed proton NMR data are also obtained. No glass transition temperatures are observed in the temperature range of the stability studies. The pulsed NMR data suggest onset of greater mobility in the solid at a water content slightly higher than BET "monolayer" level. Stability of freeze-dried solids at 25 degrees C and 40 degrees C is studied as a function of residual moisture and exposure to oxygen. Formulations with and without a glycine/mannitol excipient system are studied. Significant levels of chemical decomposition and irreversible aggregation occur under most conditions with the effects of residual water content and "headspace oxygen" strongly dependent on the formulation. At low water content with minimal oxygen in the vial headspace, the glycine/mannitol formulation yields optimum stability. However, for either high water content or high oxygen content in the vial, stability of hGH without excipients is superior. The qualitative effect of residual moisture on stability depends on the temperature of the stability study. Generally, the stability of a sample adjusted to a given water content by desorption (during freeze-drying) is identical to the stability of a sample prepared by sorption of water on to a previously highly dried sample.
Force and Touch Feedback for Virtual Reality (1996)

Could weight, temperature, and texture combine to bring simulated objects to life? Describing cutting-edge technology that will influence the way we interact with computers for years to come, this pioneering book answers yes: not only is it possible, but devices capable of providing force and tactile sensory feedback already exist. Force and Touch Feedback for Virtual Reality is the first comprehensive source of information on the design, modelling, and applications of force and tactile interfaces for VR. It is a must have for scientists, engineers, psychologists, and developers involved in VR, and for anyone who would like to gain a deeper understanding of this exciting and fast-growing field. Complete with hundreds of tables, figures, and color illustrations, Force and Touch Feedback for Virtual Reality offers * Basic information on human tactile sensing and control and feedback actuator technology * A worldwide survey of force and tactile interface devices, from the simple joystick to full-body instrumented suits based on human factor tests * Step-by-step instructions for realistic physical modelling of virtual object characteristics such as weight, surface smoothness, compliance, and temperature * A unified treatment of the benefits of the new haptic interface technology for simulation and training based on human factor tests * A detailed analysis of optimum control requirements for force and tactile feedback devices * A review of emerging applications in areas ranging from surgical training and entertainment to telerobotics and the military
Surface graft polymerization of SU-8 for bio-MEMS applications (2007)

There is currently increasing interest in using SU-8 photoresist to build microstructures for micro-electro-mechanical systems (MEMS). This report describes an effective bench-top method to modify the surface properties of SU-8 photoresist. This strategy relies on the residual epoxide groups present on the surface of SU-8 following fabrication. These epoxide groups are converted into hydroxyl groups by oxidation with a high concentration of cerium(IV) ammonium nitrate (CAN) and nitric acid. Subsequently the surface hydroxyl groups are used as initiation sites for graft polymerization catalyzed by CAN in the presence of acid. A number of water-soluble polymers including poly(acrylic acid), poly(acrylamide), poly(ethylene glycol) were successfully grafted onto SU-8. The presence of surface-linked polymers was confirmed by contact angle measurements, attenuated total reflection-Fourier transform infrared spectroscopy and toluidine blue adsorption. This method was particularly useful for tailoring the surface properties of complex or enclosed microstructures, for example, microfluidic channels. In addition the grafted polymers could serve as sites for high density protein immobilization or cell attachment on Bio-MEMS.
Increased AMPA receptor GluR1 subunit incorporation in rat hippocampal CA1 synapses during benzodiazepine withdrawal (2008)

Prolonged benzodiazepine treatment leads to tolerance and increases the risk of dependence. Flurazepam (FZP) withdrawal is associated with increased anxiety correlated with increased alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor (AMPAR)-mediated synaptic function and AMPAR binding in CA1 pyramidal neurons. Enhanced AMPAR synaptic strength is also associated with a shift toward inward rectification of synaptic currents and increased expression of GluR1, but not GluR2, subunits, suggesting augmented membrane incorporation of GluR1-containing, GluR2-lacking AMPARs. To test this hypothesis, the postsynaptic incorporation of GluR1 and GluR2 subunits in CA1 neurons after FZP withdrawal was examined by postembedding immunogold quantitative electron microscopy. The percentage of GluR1 positively labeled stratum radiatum (SR) synapses was significantly increased in FZP-withdrawn rats (88.2% +/- 2.2%) compared with controls (74.4% +/- 1.9%). In addition, GluR1 immunogold density was significantly increased by 30% in SR synapses in CA1 neurons from FZP-withdrawn rats compared with control rats (FZP: 14.1 +/- 0.3 gold particles/mum; CON: 10.8 +/- 0.4 gold particles/mum). In contrast, GluR2 immunogold density was not significantly different between groups. Taken together with recent functional data from our laboratory, the current study suggests that the enhanced glutamatergic strength at CA1 neuron synapses during benzodiazepine withdrawal is mediated by increased incorporation of GluR1-containing AMPARs. Mechanisms underlying synaptic plasticity in this model of drug dependence are therefore fundamentally similar to those that operate during activity-dependent plasticity.
Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase (2009)

Nicotinamide (NM) phosphoribosyltransferase (NMPRTase) catalyzes the reaction of NM and 5'-phosphoribosyl-1'-pyrophosphate (PRPP) to form NM mononucleotide (NMN) and pyrophosphate (PPi) in the pathway of NAD-biosynthesis. Monitoring the (1)H and (31)P NMR spectra of the reaction mixture, we found that this reaction is reversible as dictated by the equilibrium constant K = [NMN][PPi]/([NM][PRPP]) = 0.14, which agreed well with the ratio of second-order rate constants for forward and backward reactions, K = 0.16. The crystal structures of this enzyme in the free form and bound to NM and PRPP at the resolution of 2.0-2.2 A were essentially identical to that of the complex with NMN, except for some variations that could facilitate the substitution reaction by fixing the nucleophile and the leaving group for the requisite inversion of configuration at the C1' carbon of the ribose ring. In the active site near the C1' atom of the bound PRPP or NMN, there was neither negatively charged group nor waterproof environment necessary to support the feasibility of a ribo-oxocarbocation intermediate inherent in the S(N)1 mechanism. The structures and catalytic mechanism thus revealed are also discussed in connection with the multiple biological functions of NMPRTase.
A Phase IIb Study of ABT‐494, a Selective JAK‐1 Inhibitor, in Patients With Rheumatoid Arthritis and an Inadequate Response to Anti–Tumor Necrosis Factor Therapy (2016)

In patients with an inadequate response or intolerance to anti-TNF agents, ABT-494 added to MTX showed rapid, dose-dependent improvements in RA signs and symptoms, with safety and tolerability similar to those of other drugs of this class. No new AEs were identified.
Paradoxical Dampening of Anti-Islet Self-Reactivity but Promotion of Diabetes by OX40 Ligand (2003)

Costimulatory signals received by diabetogenic T cells during priming by or upon secondary encounter with autoantigen are decisive in determining the outcome of autoimmune attack. The OX40-OX40 ligand (OX40L) costimulatory pathway is known to influence T cell responses, prompting us to examine its role in autoimmune diabetes. A null allele at OX40L completely prevented diabetes development in nonobese diabetic mice and strongly reduced its incidence in a TCR transgenic model (BDC2.5). However, somewhat paradoxically, the initial activation of T cells responsive to islet beta cell Ag was slightly faster and more efficient in the absence of OX40L, with an increased degree of cell proliferation and survival in the deficient hosts. Activated T cell migration into and retention within the islets was also slightly accelerated. When challenged in vitro, splenocytes from BDC2.5.OX40L(o/o) mice showed no altered reactivity to exogenously added peptide, no bias to the Th1 or Th2 phenotype, and no alteration in T cell survival. Thus, the OX40/OX40L axis has the paradoxical effect of dampening the early activation and migration of autoimmune T cells, but sustains the long-term progression to autoimmune destruction.
Selective blockade of interleukin-6 trans-signaling improves survival in a murine polymicrobial sepsis model* (2011)

Selective inhibition of IL-6 trans-signaling by sgp130Fc has considerable potential for the treatment of sepsis and related disorders.
Guidelines for Application of Portable Work Zone Intelligent Transportation Systems (2003)

Work zone intelligent transportation systems (WZITSs) are promoted as a way to improve safety and reduce congestion at work zone locations where traditional traffic management centers do not exist. These systems usually integrate portable changeable message signs and speed sensors with a central control system that automatically determines appropriate messages that are based on current traffic conditions. Manufacturers of these systems claim that WZITSs can warn drivers of downstream congestion, alert drivers to slower speeds ahead, and suggest alternate routes on the basis of prevailing conditions. Transportation agencies are often asked to make decisions on the installation of a WZITS without the benefit of objective information on its expected performance. Relatively few operational tests of these systems have been performed, and the results are not always well documented or conclusive. Agencies need guidance to help them determine whether a WZITS system would improve safety and operations at a specific site. Applications of WZITSs are reviewed, and a series of guidelines for their deployment, based on lessons learned from past tests, is presented.