gebhart/patrepeval huggingface dataset:
Effects of steroid therapy on inflammatory cell subtypes in asthma (2009)

RATIONALE Airway inflammation in asthma is heterogeneous with different phenotypes. The inflammatory cell phenotype is modified by corticosteroids and smoking. Steroid therapy is beneficial in eosinophilic asthma (EA), but evidence is conflicting regarding non-eosinophilic asthma (NEA). OBJECTIVES To assess the inflammatory cell phenotypes in asthma after eliminating potentially confounding effects; to compare steroid response in EA versus NEA; and to investigate changes in sputum cells with inhaled corticosteroid (ICS). METHODS Subjects undertook ICS withdrawal until loss of control or 28 days. Those with airway hyper-responsiveness (AHR) took inhaled fluticasone 1000 microg daily for 28+ days. Cut-off points were > or = or <2% for sputum eosinophils and > or = or <61% for neutrophils. RESULTS After steroid withdrawal (n=94), 67% of subjects were eosinophilic, 31% paucigranulocytic and 2% mixed; there were no neutrophilic subjects. With ICS (n=88), 39% were eosinophilic, 46% paucigranulocytic, 3% mixed and 5% neutrophilic. Sputum neutrophils increased from 19.3% to 27.7% (p=0.024). The treatment response was greater in EA for symptoms (p<0.001), quality of life (p=0.012), AHR (p=0.036) and exhaled nitric oxide (p=0.007). Lesser but significant changes occurred in NEA (ie, paucigranulocytic asthma). Exhaled nitric oxide was the best predictor of steroid response in NEA for AHR (area under the curve 0.810), with an optimum cut-off point of 33 ppb. CONCLUSIONS After eliminating the effects of ICS and smoking, a neutrophilic phenotype could be identified in patients with moderate stable asthma. ICS use led to phenotype misclassification. Steroid responsiveness was greater in EA, but the absence of eosinophilia did not indicate the absence of a steroid response. In NEA this was best predicted by baseline exhaled nitric oxide.
Field emission from silicon microstructures formed by femtosecond laser assisted etching (2001)

Summary form only given. Field-emission arrays have been extensively investigated for device applications such as flat panel displays, electron multipliers and microelectronics. The use of silicon structures as emitters is especially attractive due to the low cost and availability of silicon. Previously, our group reported the formation of sharp, micron-sized conical structures in quasi-ordered arrays after irradiating a silicon surface with hundreds of femtosecond-laser pulses in an atmosphere of SF/sub 6/. These conical microstructures exhibit sharp tips with a radius of curvature /spl sim/0.25 /spl mu/m and a subtended angle of less than 20/spl deg/. Emission currents suitable for applications and comparable with current standards are achieved with no further processing beyond the laser irradiation required to form our microstructures. We report on the field emission properties of these conical microstructures through analysis of the current-voltage characteristics and the Fowler-Nordheim plots obtained for various anodecathode separations.
Structural investigations into the deactivation pathway of the CO2 reduction electrocatalyst Re(bpy)(CO)3Cl (2012)

We report a series of complexes synthesized from the chemical reduction of the fac-tricarbonyl complex Re(bpy)(CO)(3)Cl. Synthesis and characterization of [Re(bpy)(CO)(3)](2), [Re(bpy)(CO)(3)](2)(-), and Re(bpy)(CO)(3)(-) are presented. The Re(bpy)(CO)(3)(-) anion has long been postulated as the active species that reacts with carbon dioxide in the electrochemical reduction of CO(2).
<title>Color neutral rugate filters</title> (1993)

This paper describes a transmissive rugate filter which is designed to reflect a portion of the visible spectrum and yet not appear to have a dominant color. The filter design criteria were chosen so that the filter rejects portions of the visible spectrum from 0.38 to 0.78 microns. Observing a scene through this type of optical filter one perceives it to be devoid of coloration, i.e., color neutral, albeit it is somewhat darker. The design constraints assume a solar light source. The eye bounds the wavelength range over which perceived coloration is affected. For this work the spectral characteristics of both the incident light and the standard human eye determine the nature of the spectral tailoring of the reflection bands. Rugate filter design and fabrication technology permits a very wide latitude in the number, location, bandwidth, and peak height of all reflection bands. The result is a color neutral rugate filter having reflection bands tailored to provide the human user with maximum color discrimination capability.
Short and Novel Stereospecific Synthesis of Trisubstituted 2,5-Diketopiperazines (2005)

Novel syntheses of chiral trisubstituted 2,5-diketopiperazines using multicomponent Ugi reactions were developed.
Gene amplification and drug resistance in mammalian cells. (1982)

Stepwise selection of cultured hamster and mouse cells in progressively increasing concentrations of methotrexate results in highly resistant cells. The resistance results from increased levels of dihydrofolate reductase, the target of methotrexate action in cells. The elevated levels of this enzyme, in turn, results from selective amplification of DNA sequences coding for the enzyme. In some cell lines, the amplified genes are stable when cells are subsequently grown in the absence of methotrexate; these genes are present and localized to a specific region of a chromosome(s). In other cell lines, the amplified genes are unstable and are localized to extrachromosomal elements. These findings are summarized, and mechanisms for the generation of amplified genes are discussed.
Trk Receptors: Roles in Neuronal Signal Transduction (2003)

Trk receptors are a family of three receptor tyrosine kinases, each of which can be activated by one or more of four neurotrophins-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophins 3 and 4 (NT3 and NT4). Neurotrophin signaling through these receptors regulates cell survival, proliferation, the fate of neural precursors, axon and dendrite growth and patterning, and the expression and activity of functionally important proteins, such as ion channels and neurotransmitter receptors. In the adult nervous system, the Trk receptors regulate synaptic strength and plasticity. The cytoplasmic domains of Trk receptors contain several sites of tyrosine phosphorylation that recruit intermediates in intracellular signaling cascades. As a result, Trk receptor signaling activates several small G proteins, including Ras, Rap-1, and the Cdc-42-Rac-Rho family, as well as pathways regulated by MAP kinase, PI 3-kinase and phospholipase-C-gamma (PLC-gamma). Trk receptor activation has different consequences in different cells, and the specificity of downstream Trk receptor-mediated signaling is controlled through expression of intermediates in these signaling pathways and membrane trafficking that regulates localization of different signaling constituents. Perhaps the most fascinating aspect of Trk receptor-mediated signaling is its interplay with signaling promoted by the pan-neurotrophin receptor p75NTR. p75NTR activates a distinct set of signaling pathways within cells that are in some instances synergistic and in other instances antagonistic to those activated by Trk receptors. Several of these are proapoptotic but are suppressed by Trk receptor-initiated signaling. p75NTR also influences the conformations of Trk receptors; this modifies ligand-binding specificity and affinity with important developmental consequences.
A Natural Antibody to Oxidized Cardiolipin Binds to Oxidized Low-Density Lipoprotein, Apoptotic Cells, and Atherosclerotic Lesions (2006)

These data demonstrate that some aCL antibodies are highly conserved natural antibodies binding to oxCL in oxLDL, apoptotic cells, and atherosclerotic lesions. This suggests that oxCL is one of the pathogen-associated molecular patterns of innate immunity and gives insight into the pathogenic events of diseases with increased titers of aCL antibodies.
The prostate: An increasing medical problem (1990)

The prostate gland is the major site of medical problems in the U.S. male. Surgery for benign prostatic hyperplasia is the most common surgical procedure performed in males, and the total cost for this surgery exceeds 1 billion dollars per year. The incidence of and mortality from prostate cancer are increasing yearly. Prostate cancer now exceeds lung cancer as the most commonly diagnosed cancer in males and is the second leading cause of male cancer deaths. Of all tumors, the prevalence of prostate cancer increases the most rapidly with age. A shift in age distribution favoring an older population will lead to an increase in the number of patients diagnosed with prostate cancer in the United States. It is estimated that by the year 2000 there will be a 37% increase in prostate cancer deaths per year and a 90% increase in prostate cancer cases per year. Although the factors responsible for the development and progression of prostate cancer to a clinically manifest form are not known, there is evidence that environmental factors may play a role. It will be important for the future to focus on the etiological factors that may lead to a decrease in the prevalence of prostatic tumors.
Changes in birefringence as markers of thermal damage in tissues (1989)

Light microscopy using polarized transmission illumination of routinely stained histologic sections shows changes of the native birefringence of certain tissue constituents when heated by laser irradiation or electrosurgical current. The naturally occurring birefringence of cardiac muscle disappears permanently when the muscle is frozen, thawed, and heated to temperatures in excess of 42 degrees C in vitro. This loss of birefringence is produced with temperatures at which other morphologic thermal changes are hard to detect; thus, it is a low-temperature tissue marker which can be used to observe the extent of thermal damage in tissues. Partial loss of the native birefringence of collagen occurs in canine urinary bladder coagulated by laser irradiation and pericardium heated with electrodes. In addition, thermally coagulated collagens have variable birefringence color shifts when compared to the adjacent unaffected collagens in stained histologic sections. The gradual birefringence color changes are seen at tissue temperatures higher than those at which the thermally induced hyalinization (coagulation) of collagen usually occurs (about 60-70 degrees C), but below those at which carbonization is seen (200+ degrees C). Birefringence changes can be measured to test mathematical models of thermal damage necessary for development of dosimetry models in medical applications of laser irradiation.
Prostate cancer stem/progenitor cells: Identification, characterization, and implications (2006)

Several solid tumors have now been shown to contain stem cell-like cells called cancer stem cells (CSC). These cells, although generally rare, appear to be highly tumorigenic and may be the cells that drive tumor formation, maintain tumor homeostasis, and mediate tumor metastasis. In this Perspective, we first provide our insight on how a CSC should be defined. We then summarize our current knowledge of stem/progenitor cells in the normal human prostate (NHP), an organ highly susceptible to hyperproliferative diseases such as benign prostate hyperplasia (BPH) and prostate cancer (PCa). We further review the evidence that cultured PCa cells, xenograft prostate tumors, and patient tumors may contain stem/progenitor cells. Along with our discussion, we present several methodologies that can be potentially used to identify putative tumor-reinitiating CSC. Finally, we present a hypothetical model for the hierarchical organization of human PCa cells and discuss the implications of this model in helping understand prostate carcinogenesis and design novel diagnostic, prognostic, and therapeutic approaches.
The Role of Apaf-1 in Programmed Cell Death: From Worm to Tumor. (2003)

Apoptosis or programmed cell death is an important process to eliminate unnecessary or hazardous cells. Apaf-1, a mammalian homologue of CED-4 of C. elegans, is the essential adaptor molecule in the mitochondrial pathway of apoptosis. Mice lacking Apaf-1 show accumulation of neurons in the developing central nervous system due to reduced apoptosis. Apaf-1-deficient cells are remarkably resistant to various apoptotic stimuli. Apaf-1-mediated apoptosis plays a role in the prevention of tumorigenesis. However, Apaf-1-independent cell death pathways are also indicated. In this review, we will summarize what has been learned about the role of Apaf-1 by biochemical and genetical approaches.
Discoidin domain receptor 1 expression in activated T cells is regulated by the ERK MAP kinase signaling pathway (2011)

The expression and function of discoidin domain receptor 1 (DDR1) in T cells are still poorly explored. We have recently shown that activation of primary human T cells via their T cell receptor leads to increased expression of DDR1, which promoted their migration in three-dimensional collagen. In the present study, we provide evidence that activated T cells bind collagen through DDR1. We found that the DDR1:Fc blocking molecule significantly reduced the ability of activated T cells to bind soluble biotinylated collagen. However, DDR1:Fc had no impact on the adhesion of activated T cells to collagen and overexpression of DDR1 in Jurkat T cells did not enhance their adhesion. Together, our results indicate that DDR1 can promote T cell migration without enhancing adhesion to collagen, suggesting that it can contribute to the previously described amoeboid movement of activated T cells in collagen matrices. Our results also show that CD28, in contrast to IL-2 expression, did not costimulate the expression of DDR1 in primary human T cells. Using specific inhibitors, we demonstrated that TCR-induced expression of DDR1 in T cells is regulated by the Ras/Raf/ERK MAP Kinase and PKC pathways but not by calcium/calcineurin signaling pathway or the JNK and P38 MAP Kinases. Thus, our study provides additional insights into the physiology of DDR1 in T cells and may therefore further our understanding of the regulatory mechanisms of T cell migration.
A graph-constructive approach to solving systems of geometric constraints (1997)

A graph-constructive approach to solving systems of geometric constraints capable of effeciently handling well-constrained, overconstrained, and underconstrained configurations is presented. The geometric constraint solver works in two phases: in the analysis phase the constraint graph is analyzed and a sequence of elementary construction steps is derived, and then in the construction phase the sequence of construction steps in actually carried out. The analysis phase of the algorithm is described in detail, its correctness is proved, and an efficient algorith to realized it is presented. The scope of the graph analysis is then extended by utilizing semantic information in the form of anlge derivations, and by extending the repertoire of the construction steps. Finally, the construction phase is briefly discussed.
Management of nonresponse to rituximab in rheumatoid arthritis: Predictors and outcome of re‐treatment (2010)

RA patients whose disease did not respond to an initial cycle of rituximab have higher circulating preplasma cell numbers at baseline and incomplete depletion. Our findings indicate that an additional cycle of rituximab administered prior to total B cell repopulation enhances B cell depletion and clinical responses.
Overexpression of HTRA1 Leads to Down-Regulation of Fibronectin and Functional Changes in RF/6A Cells and HUVECs (2012)

Multiple genetic studies have suggested that high-temperature requirement serine protease (HTRA1) is associated with polypoidal choroidal vasculopathy (PCV). To date, no functional studies have investigated the biological effect of HTRA1 on vascular endothelial cells, essential vascular components involved in polypoidal vascular abnormalities and arteriosclerosis-like changes. In vitro studies were performed to investigate the effect of HTRA1 on the regulation of fibronectin, laminin, vascular endothelial growth factor (VEGF), platelet derived growth factor receptor (PDGFR) and matrix metalloparoteinases 2 (MMP-2) and the role of HTRA1 in choroid-retina endothelial (RF/6A) and human umbilical vein endothelial (HUVEC) cells. Lentivirus-mediated overexpression of HTRA1 was used to explore effects of the protease on RF/6A and HUVEC cells in vitro. HTRA1 overexpression inhibited the proliferation, cell cycle, migration and tube formation of RF/6A and HUVEC cells, effects that might contribute to the early stage of PCV pathological lesions. Fibronectin mRNA and protein levels were significantly down-regulated following the upregulation of HTRA1, whereas the expressions of laminin, VEGF and MMP-2 were unaffected by alterations in HTRA1 expression. The decreased biological function of vascular endothelial cells and the degradation of extracellular matrix proteins, such as fibronectin, may be involved in a contributory role for HTRA1 in PCV pathogenesis.
Magnetic resonance imaging of brain function. (1994)

New techniques for imaging of brain function are described, which utilize magnetic resonance imaging. Echo-planar imaging (EPI), the preferred method, is introduced and technical issues are discussed. Two recent approaches for measurement of blood flow are explained: contrast agent bolus tracking and black blood perfusion. An intrinsic contrast technique, which utilizes the paramagnetism of deoxyhemoglobin, is presented. Results from experiments on functional imaging of the human brain are shown, and the specific advantages of MRI for this purpose are discussed.
Stabilization of vaccines: Lessons learned (2010)

(2010). Stabilization of vaccines: Lessons learned. Human Vaccines: Vol. 6, No. 3, pp. 227-231.
Impedance spectroscopy on stretchable microelectrode arrays (2010)

We are reporting on the fabrication and electrical characterization of stretchable polydimethylsiloxane (PDMS) based microelectrode arrays for recording of neuronal action potentials. Electrodes are immersed in phosphate buffered saline solution. Their electrical impedance spectra are recorded as a function of uniaxial macroscopic strain applied using a custom built automated stretcher. We propose a model to account for the physical phenomena responsible for electrical conduction in the bulk electrode and at the metal–electrolyte interface. Electrodes with active area dimensions of 100×140 μm2 maintain an impedance of approximately 1 MΩ at 1 kHz when cycled to 20% strain.
Origin and regulation of a disease-specific autoantibody response. Antigenic epitopes, spectrotype stability, and isotype restriction of anti-Jo-1 autoantibodies. (1990)

Anti-Jo-1 antibodies (AJoA), which bind to and inhibit the activity of histidyl-transfer RNA synthetase (HRS), are found in a genetically and clinically distinct subset of myositis patients. This specificity suggests that understanding the antigenic epitopes and immunoregulation governing the production of AJoA may result in clues to disease pathogenesis. Limited digestion of human HRS by V8 protease resulted in four major antigenic polypeptides of 35, 34, 21, and 20 kD; digestion with subtilisin gave four fragments of the same sizes and two additional major antigenic polypeptides of 28 and 17 kD. Sera from 12 AJoA positive patients reacted indistinguishably with these proteolytic fragments by Western blotting, and AJoA elution studies suggested a common epitope(s) on all six. Isoelectric focusing showed a different polyclonal pattern of AJoA in each patient, although serial analyses in individual patients revealed stable AJoA spectrotypes over years of observation. Enzyme-linked immunosorbent assays showed that the AJoA response was mainly restricted to the IgG1 heavy chain isotype. The levels of IgG1 AJoA varied in proportion to disease activity over time but were independent of total IgG1 levels, and three patients became AJoA negative as their myositis remitted after treatment. These findings suggest that AJoA are induced by an antigen-driven mechanism, bind to a common epitope or epitopes on HRS, and are modulated by an immune response closely linked to that which is responsible for myositis in these patients.
Cyclosporin A and cyclosporin SDZ PSC 833 enhance anti-CD5 ricin A- chain immunotoxins in human leukemic T cells (1994)

Recent studies have shown that cyclosporin A (CsA) may affect ricin A-chain immunotoxin (RTA-IT) therapy. In this study, we evaluated the ability of CsA and its nonimmunosuppressive analog, SDZ PSC 833, to enhance anti-CD5 T101 RTA-ITs in vitro. Both 4 mumol/L CsA and 4 mumol/L SDZ PSC 833 significantly and specifically enhanced the cytotoxic activity of T101 RTA-IT on the human lymphoblastic T-cell line, CEM III (101-fold and 105-fold, respectively). Furthermore, these Cs also enhanced the cytotoxicity of the more potent T101 F(ab')2 RTA-IT (ninefold and eightfold, respectively). The effect of human plasma, originating from four patients enrolled in a phase I high-dose CsA regimen, was examined on T101 RTA-IT cytotoxicity on CEM III cells. In each case, with plasma CsA levels between 3,090 and 4,860 ng/mL (2.5 to 4 mumol/L), a significant increase in T101 RTA-IT-mediated cytotoxicity was observed ranging from 31% to 60%. Neither CsA nor SDZ PSC 833 affected the rate of RTA-IT binding, internalization, intracellular trafficking, or degradation. Analysis of internalized T101 RTA-IT molecules showed that these were essentially intact, which suggests that these enhancers may act only on a small population of RTA-ITs that escapes present investigational techniques. In conclusion, because the concentrations used are clinically achievable, Cs appear to be promising agents for in vivo enhancement of RTA-ITs.
Covered Stents for Prevention of Restenosis (1996)

The uncovered stent induces little neointimal proliferation around the stent wires. The insertion of stents covered with PEM into the rabbit aorta was accompanied by a strong thrombotic reaction, despite sufficient anticoagulation. Dacron-covered nitinol stents showed a surprisingly high restenosis rate after 9 months of follow-up. Further research concerning the in vivo properties of new covering materials is mandatory before routine vascular clinical application.
Conductivity, Doping, and Redox Chemistry of a Microporous Dithiolene-Based Metal−Organic Framework (2010)

The new microporous metal−organic framework Cu[Ni(pdt)2] (pdt2− = pyrazine-2,3-dithiolate) is demonstrated to have an optical bandgap, p-type semiconductivity, and redox activity. The compound can be doped by using I2 as an oxidant, leading to an increase in conductivity by 4 orders of magnitude with retention of porosity.