gebhart/patrepeval huggingface dataset:
Effect of long term treatment with salmeterol on asthma control: a double blind, randomised crossover study (1997)

In subjects who adjusted their inhaled steroid treatment according to guidelines the addition of salmeterol 50 micrograms twice daily was associated with a reduction in inhaled steroid use and improved lung function and symptom control.
An experimental study of the regulation of glycolytic oscillations in yeast (2013)

We have studied oscillating glycolysis in the strain BY4743 and isogenic strains with deletions of genes encoding enzymes in glycolysis, mitochondrial electron transport and ATP synthesis. We found that deletion of the gene encoding the hexokinase 1 isoform does not affect the oscillations while deletion of the gene encoding the hexokinase 2 isoform results in oscillations with smaller amplitude. The latter is associated with an almost 50% decrease in hexokinase activity. Deletions in the genes encoding the α- and β-subunits of phosphofructokinase abolish the oscillations entirely. This loss in oscillatory activity is associated with a fourfold decrease in phosphofructokinase activity. Deletions of genes encoding subunits of the F1F0 ATPase also inhibit the oscillations in accordance with earlier studies using for example inhibitors. Finally, we identified an apparently new control point involving the mitochondrial cytochrome c oxidase. The latter is difficult to explain as oscillatory activity entails 100% inhibition of this enzyme. The mitochondria of this strain seem to have normal F1F0 ATPase activity. Overall these results support earlier experimental and model studies suggesting that in addition to processes within glycolysis also processes outside this pathway contribute to the control of the oscillatory behaviour.
Transdermal Testosterone Delivery: Comparison Between Scrotal and Nonscrotal Delivery Systems (1999)

The purpose of this investigation was to study the bioequivalence of two testosterone transdermal delivery systems (T-TDSs). Testoderm, designed to deliver testosterone through scrotal skin, and Androderm, designed for nonscrotal permeation. In vitro permeation and release kinetics as well as in vivo pharmacokinetics in the castrated Yucatan miniature swine (minipigs) model of both T-TDSs were studied side by side under the same experimental conditions. In vitro skin permeation kinetics studies demonstrated that testosterone permeates through minipig dorsal skin at zero-order kinetics from both T-TDSs. The nonscrotal T-TDS, however, has a permeation rate which is approximately 13 times higher than that for the scrotal T-TDS. The release of testosterone from the nonscrotal T-TDS showed a biphasic release profile between cumulative amount released and time, whereas a monophasic release profile between cumulative amount released and square root of time was observed for the scrotal T-TDS. Pharmacokinetic analysis of plasma testosterone profiles in minipigs indicated a significant difference (p < 0.001) in daily dose of testosterone delivered (1.20 versus 4.83 mg/day), maximum concentration (Cmax) (54.2 versus 218.0 ng/dl), and area under concentration-time curve (AUC0-28)[665 versus 3208 (ng/dl) x hr] between these T-TDSs. However, there is no difference in time to reach Cmax mean residence time, and daily-delivered-dose-normalized Cmax and AUC0-28. The difference in pharmacokinetic profiles resulted from the difference in daily doses delivered, which could be attributed remarkably to the difference in permeation rate (approximately 13-fold) between the nonscrotal and scrotal T-TDSs.
Activation of PPARδ alters lipid metabolism in db/db mice (2000)

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, which heterodimerize with the retinoid X receptor and bind to peroxisome proliferator response elements in the promoters of regulated genes. Despite the wealth of information available on the function of PPARalpha and PPARgamma, relatively little is known about the most widely expressed PPAR subtype, PPARdelta. Here we show that treatment of insulin resistant db/db mice with the PPARdelta agonist L-165041, at doses that had no effect on either glucose or triglycerides, raised total plasma cholesterol concentrations. The increased cholesterol was primarily associated with high density lipoprotein (HDL) particles, as shown by fast protein liquid chromatography analysis. These data were corroborated by the chemical analysis of the lipoproteins isolated by ultracentrifugation, demonstrating that treatment with L-165041 produced an increase in circulating HDL without major changes in very low or low density lipoproteins. White adipose tissue lipoprotein lipase activity was reduced following treatment with the PPARdelta ligand, but was increased by a PPARgamma agonist. These data suggest both that PPARdelta is involved in the regulation of cholesterol metabolism in db/db mice and that PPARdelta ligands could potentially have therapeutic value.
Osteoclast diseases (2003)

Osteoclasts are the only cells capable of resorbing mineralised bone, dentine and cartilage. Osteoclasts act in close concert with bone forming osteoblasts to model the skeleton during embryogenesis and to remodel it during later life. A number of inherited human conditions are known that are primarily caused by a defect in osteoclasts. Most of these are rare monogenic disorders, but others, such as the more common Paget's disease, are complex diseases, where genetic and environmental factors combine to result in the abnormal osteoclast phenotype. Where the genetic defect gives rise to ineffective osteoclasts, such as in osteopetrosis and pycnodysostosis, the result is the presence of too much bone. However, the phenotype in many osteoclast diseases is a combination of osteosclerosis with osteolytic lesions. In such conditions, the primary defect is hyperactivity of osteoclasts, compensated by a secondary increase in osteoblast activity. Rapid progress has been made in recent years in the identification of the causative genes and in the understanding of the biological role of the proteins encoded. This review discusses the known osteoclast diseases with particular emphasis on the genetic causes and the resulting osteoclast phenotype. These human diseases highlight the critical importance of specific proteins or signalling pathways in osteoclasts.
Human Platelet Factor 4 and Its C-Terminal Peptides: Heparin Binding and Clearance from the Circulation (1990)

Human platelet factor 4 (PF4), a high affinity heparin binding protein, is released from stimulated platelets and stored at vascular sites, predominantly in liver, from where it can be brought back into circulation by heparin. We attempted to define structural requirements for PF4 binding to heparin and for the pattern of its clearance from the circulation. Intact PF4 bound strongly to heparin agarose and was eluted at 1.4 M NaCl, while reduced PF4 and PF4 C-terminal peptides PF4 (47-70) and PF4 (58-70) bound weakly and were eluted at 0.2-0.5 M NaCl. 125I-radiolabeled intact PF4, reduced PF4 and C-terminal PF4 peptides injected into rabbits were cleared from the circulation in a biphasic pattern with components having half-life time of 1-2 min and 20-140 min. Heparin eliminated the fast component of PF4 clearance, but it did not affect clearance of reduced PF4 or C-terminal PF4 peptides. In contrast to reduced PF4 and PF4 (47-70), intact PF4 that accumulated in the liver and spleen, was displaced by heparin into circulating blood. In conclusion, specific binding sites and native conformation of the molecule are critical for high affinity PF4 binding to insolubilized heparin and for a pattern of PF4 clearance from the circulation in the presence of heparin.
Analysis of halftone dot profile and aliasing in the discrete binary representation of images* (1977)

Screening techniques are widely used in the binary display of continuous-tone images by digital output devices. The quality of the halftone image resulting from such a nonlinear transformation is dependent on the dot profile employed. In the Fourier domain, aliasing degrades the halftone image. The relationship between image quality and dot profile is studied from this point of view. For a well-known dot profile, it is shown analytically how aliasing is suppressed, and that quantization contouring may be eliminated without an appreciable increase in aliasing.
Theoretical performance of voltage multiplier circuits (1971)

An expression for the equivalent source resistance of the capacitor diode voltage multiplier circuit is derived. The source resistance is found to increase as the cube of the multiplication factor, explaining the poor regulation observed with large multiplication. The distribution of capacitors that minimizes source resistance is presented. Good regulation is shown to be necessary for high efficiency, and to require relatively larger capacitors than needed for ripple filtering.
Negative regulation of vascular smooth muscle cell migration by blood shear stress (2006)

Vortex blood flow with reduced blood shear stress in a vein graft has been hypothesized to promote smooth muscle cell (SMC) migration and intimal hyperplasia, pathological events leading to vein graft restenosis. To demonstrate that blood shear stress regulates these processes, we developed a modified vein graft model where the SMC response to reduced vortex blood flow was compared with that of control vein grafts. Vortex blood flow induced SMC migration and neointimal hyperplasia in control vein grafts, whereas reduction of vortex blood flow in the modified vein graft strongly suppressed these effects. A venous polymer implant with known fluid shear stress was employed to clarify the molecular mechanism of shear-dependent SMC migration in vivo. In the polymer implant, the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and myosin light chain kinase (MLCK), found primarily in SMCs, increased from day 3 to day 5 and returned toward the control level from day 5 to day 10, with the peak phosphorylation associated with the maximal speed of SMC migration. Treatment with PD-98059 (an inhibitor specific to the ERK1/2 activator MEK1/2) significantly suppressed the phosphorylation of MLCK, suggesting a role for ERK1/2 in regulating the activity of MLCK. Treatment with PD-98059 or ML-7 (an inhibitor specific to MLCK) reduced shear stress-dependent SMC migration, resulting in an SMC distribution independent of fluid shear stress. These results suggest that fluid shear stress regulates SMC migration via the mediation of ERK1/2 and MLCK.
Waveguide cavity surface-enhanced Raman scattering (2006)

It is shown that surface-enhanced electromagnetic scattering can occur in small recessed metallic-walled structures through resonance of a propagating waveguide mode. Analytical solutions for simplified geometries provide a means to explain numerical simulations and, through a field-enhanced dipole moment, surface-enhanced Raman scattering. Material and geometry requirements result from the treatment.
Native Laser Lithography of His-Tagged Proteins by Uncaging of Multivalent Chelators (2010)

We report a generic approach for targeting proteins into micropatterns by in situ laser lithography. To this end, we have designed a photocleavable oligohistidine peptide for caging tris(nitrilo triacetic acid) (tris-NTA) groups on surfaces by multivalent interactions. Local photofragmentation of the peptide by UV illumination through a photomask or by a confocal laser beam uncages tris-NTA, thus generating free binding sites for rapid, site-specific capturing of His-tagged proteins into micropatterns. Iterative writing of proteins by laser lithography enabled for assembly of multiplexed functional protein microstructures on surfaces. Thus, versatile, user-defined protein micropatterns can be assembled under physiological conditions with a standard confocal laser-scanning microscope.
Macrophage migration inhibitory factor in rheumatoid arthritis: Evidence of proinflammatory function and regulation by glucocorticoids (1999)

These data represent the first demonstration of the cytokine MIF in human autoimmune disease and suggest MIF as a potential therapeutic target in RA.
기독교대학 교양교육에 대한 인식 및 만족도에 관한 연구: 아세아연합신학 대학교를 중심으로 (2017)

대학에서의 교양교육은 갈수록 중요성이 더해가고 있으며 기독교정신과 기독교세계관을 지닌 지도자를 양성한다는 목적으로 설립된 대다수의 기독교대학에서는 더욱 더 중요한 교육의 영역으로 인정받고 있다. 본 연구는 교양교육의 본질과 올바른 방향을 점검함과 동시에, 현재 아세아연합신학대학교에서 진행되고 있는 교양교육에 대한 학생들의 인식과 만족도를 조사하기 위해 인터넷을 통한 진행된 설문조사를 진행하였다. 먼저 교양교육의 영역별로 학생들이 얼마나 많은 과목을 수강했는지 조사한 결과 외국어 영역과 인문과학 영역이 가장 높았고, 과학과 기술 영역과 사회봉사 영역이 가장 낮게 나타났다. 교양교육에 대해 학생들은 중요하게 생각하는 정도에 비해 만족도가 떨어지고 있음을 알 수 있었는데 학생들이 가장 시급하게 개선을 바라는 항목은 `보다 다양한 교양과목이 학생들에게 제공되는 것`이었다. 또한 학생들이 교양과목을 저학년에 들어야 한다는 것에 대해 중요하게 생각하고 있지 않았고, 또 그에 대한 만족도도 낮았다. 교양교육을 담당하는 교수들의 교수방법이나 교 과 과정 운영방식에 대한 학생들의 인식을 보면, 교수들이 학생들에게 열정적으로 가르치고 또 설명도 잘 하는 것으로 나타났다. 그러나 중요도-만족도 분 석(Importance-Performance Analysis: IPA) 결과 학생이 수업에 흥미를 가질 수 있도록 동기를 유발하는 부분에 있어서는 개선이 필요함을 알 수 있었다. 마지 막으로 학습성과에 대한 인식을 보면 대체로 학생들이 중요하게 생각하고 있는 지식이나 능력은 잘 교육되고 있었으나, 학생들이 중요하게 생각하고 있지 않는 영역은 그 만족도 역시 떨어지는 모습으로 나타나고 있었다. 특히 수리적 (수량적) 문제 분석 능력은 가장 낮은 중요도와 만족도를 기록하였다
Gleason Grading and Volume Estimation in Prostate Needle Biopsy Specimens (2005)

The Gleason grading system for prostate cancer is a powerful tool that can help choose therapy and predict outcome for patients. The clinical use and problem areas of the Gleason grading system are reviewed. The issues discussed include grade discrepancies between prostate biopsy and resection specimens, grading small foci of tumor, diagnosing and grading cribriform lesions, reporting the grade when 3 grades of cancer are present in a specimen, and assignment of grade when multiple cores of differing grades are present. Finally, differing ways of communicating tumor volume and the percentage of high-grade carcinoma in prostate biopsy cores are considered.
Cyclic meso-ionic compounds. Part IX. Synthesis, spectroscopic properties, and chemistry of 1,3,4-thiadiazolium-2-olates and 1,3,4-oxadiazolium-2-thiolates (1974)

The synthesis, spectroscopic properties, and reactions of 1,3,4-thiadiazolium-2-olates (III) and 1,3,4-oxadiazolium-2-thiolates (IV) are reported. The results establish the existence of corresponding pairs of isomeric meso-ionic compounds whose isomerisation [(IV)→(III)] involves exchange between endocyclic and exocyclic hetero-atoms.
Protein Engineering (1983)

The prospects for protein engineering, including the roles of x-ray crystallography, chemical synthesis of DNA, and computer modelling of protein structure and folding, are discussed. It is now possible to attempt to modify many different properties of proteins by combining information on crystal structure and protein chemistry with artificial gene synthesis. Such techniques offer the potential for altering protein structure and function in ways not possible by any other method.
Microfluidic chips for the crystallization of biomacromolecules by counter-diffusion and on-chip crystal X-ray analysis (2009)

Microfluidic devices were designed to perform on micromoles of biological macromolecules and viruses the search and the optimization of crystallization conditions by counter-diffusion, as well as the on-chip analysis of crystals by X-ray diffraction. Chips composed of microchannels were fabricated in poly-dimethylsiloxane (PDMS), poly-methyl-methacrylate (PMMA) and cyclo-olefin-copolymer (COC) by three distinct methods, namely replica casting, laser ablation and hot embossing. The geometry of the channels was chosen to ensure that crystallization occurs in a convection-free environment. The transparency of the materials is compatible with crystal growth monitoring by optical microscopy. The quality of the protein 3D structures derived from on-chip crystal analysis by X-ray diffraction using a synchrotron radiation was used to identify the most appropriate polymers. Altogether the results demonstrate that for a novel biomolecule, all steps from the initial search of crystallization conditions to X-ray diffraction data collection for 3D structure determination can be performed in a single chip.
Vesicle Permeabilization by Protofibrillar α-Synuclein:  Implications for the Pathogenesis and Treatment of Parkinson's Disease (2001)

Fibrillar alpha-synuclein is a component of the Lewy body, the characteristic neuronal inclusion of the Parkinson's disease (PD) brain. Both alpha-synuclein mutations linked to autosomal dominant early-onset forms of PD promote the in vitro conversion of the natively unfolded protein into ordered prefibrillar oligomers, suggesting that these protofibrils, rather than the fibril itself, may induce cell death. We report here that protofibrils differ markedly from fibrils with respect to their interactions with synthetic membranes. Protofibrillar alpha-synuclein, in contrast to the monomeric and the fibrillar forms, binds synthetic vesicles very tightly via a beta-sheet-rich structure and transiently permeabilizes these vesicles. The destruction of vesicular membranes by protofibrillar alpha-synuclein was directly observed by atomic force microscopy. The possibility that the toxicity of alpha-synuclein fibrillization may derive from an oligomeric intermediate, rather than the fibril, has implications regarding the design of therapeutics for PD.
A Gas-Actuated Anthropomorphic Prosthesis for Transhumeral Amputees (2008)

This paper presents the design of a gas-actuated anthropomorphic arm prosthesis with 21 degrees of freedom and nine independent actuators. The prosthesis utilizes the monopropellant hydrogen peroxide as a gas generator to power nine pneumatic type actuators. Of the nine independent actuators, one provides direct- drive actuation of the elbow, three provide direct-drive actuation for the wrist, and the remaining five actuate an underactuated 17 degree of freedom hand. This paper describes the design of the prosthesis, including the design of small-scale high-performance servovalves, which enable the implementation of the monopropellant concept in a transhumeral prosthesis. Experimental results are given characterizing both the servovalve performance and the force and/or motion control of various joints under closed-loop control.
Presidential Address to The American Association of Immunologists. The road less traveled by: the role of innate immunity in the adaptive immune response. (1998)

The Road Not Taken 

Two roads diverged in a yellow wood,

And sorry I could not travel both

And be one traveler, long I stood

And looked down one as far as I could

To where it bent in the undergrowth;

Then took the other, as just as fair,

And having perhaps the better claim,

Because it was
Oxide breakdown model for very low voltages (1993)

3 Volt MOS ICs have arrived and the need to understand low voltage Si02 breakdown has taken on new urgency. Previous gate oxide lietime modeling has been based upon empirical 1/E or E models, however they are nct known to account for low voltage breakdown in ultra-thin oxides. We demonstrate a model based upon anode hot hole injection which explains the "thin" oxide breakdown that occurs at oxide voltages as low as 2.5 Volts, while converging to the "thick" oxide (x <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ox</sub> ⩾ 12 nm), high-voltage breakdown of as well.
Porous silicon formation mechanisms (1992)

Recent reports describing photoluminescence in porous silicon have heightened the level of interest in it as a unique electronic material, and have created a need for a more complete understanding of the mechanism of porous silicon formation. The various models describing porous silicon formation are reviewed and the known electrochemical and morphological properties are discussed with the intention of unifying the different models into a comprehensive explanation for the formation of a porous structure in silicon. Because the specific surface dissolution chemistry is critical for a complete understanding of pore formation, some of the more prominent dissolution reactions are also reviewed and their relative importance to pore generation and morphology is discussed. Some aspects of the recently reported quantum effects are also reviewed. Because the mechanism of porous silicon formation involves a wide range of interdisciplinary fields, a considerable number of analogies and examples to related phenomena are also presented throughout the review to aid comprehension.
A 1H‐NMR study of the solution conformation of secretin resonance assignment and secondary structure (1987)

The solution conformation of the 27 residue polypeptide hormone secretin has been investigated by 1H-NMR spectroscopy under conditions where it adopts a fully ordered structure as judged by circular dichroism spectroscopy, namely in an aqueous solution of 40% (v/v) trifluoroethanol. Using a combination of two-dimensional NMR techniques the 1H-NMR spectrum of secretin is completely assigned and its secondary structure is determined from a qualitative interpretation of the nuclear Overhauser enhancement data. It is shown that under these conditions secretin adopts a conformation consisting of an N-terminal irregular strand (residues 1-6) followed by two helices (residues 7-13 and 17-25) connected by a 'half-turn' (residues 14-16); the last two residues (26 and 27) are again irregular. This conformation is shown to be very similar to that of glucagon in perdeuterated dodecylphosphocholine micelles and to that of the active 1-29 fragment of growth hormone releasing factor in 30% (v/v) trifluoroethanol:
Prevention of vascular graft occlusion and thrombus-associated thrombin generation by inhibition of factor XI (2008)

The protease thrombin is required for normal hemostasis and pathologic thrombogenesis. Since the mechanism of coagulation factor XI (FXI)-dependent thrombus growth remains unclear, we investigated the contribution of FXI to thrombus formation in a primate thrombosis model. Pretreatment of baboons with a novel anti-human FXI monoclonal antibody (aXIMab; 2 mg/kg) inhibited plasma FXI by at least 99% for 10 days, and suppressed thrombin-antithrombin (TAT) complex and beta-thromboglobulin (betaTG) formation measured immediately downstream from thrombi forming within collagen-coated vascular grafts. FXI inhibition with aXIMab limited platelet and fibrin deposition in 4-mm diameter grafts without an apparent increase in D-dimer release from thrombi, and prevented the occlusion of 2-mm diameter grafts without affecting template bleeding times. In comparison, pretreatment with aspirin (32 mg/kg) prolonged bleeding times but failed to prevent graft occlusion, supporting the concept that FXI blockade may offer therapeutic advantages over other antithrombotic agents in terms of bleeding complications. In whole blood, aXIMab prevented fibrin formation in a collagen-coated flow chamber, independent of factor XII and factor VII. These data suggest that endogenous FXI contributes to arterial thrombus propagation through a striking amplification of thrombin generation at the thrombus luminal surface.