gebhart/patrepeval huggingface dataset:
Phagocytosis of leprosy bacilli is mediated by complement receptors CR1 and CR3 on human monocytes and complement component C3 in serum. (1990)

Mycobacterium leprae, an obligate intracellular pathogen, invades and multiplies within host mononuclear phagocytes. To understand M. leprae invasion better, we have investigated the role of phagocyte receptors and bacterium-bound ligands in phagocytosis of M. leprae by human monocytes. Complement receptors CR1 and CR3 mediate adherence and phagocytosis of M. leprae in nonimmune serum. Two MAbs used in combination against CR3 inhibit adherence by up to 90 +/- 3%. Two MAbs used in combination against CR1 and CR3 inhibit adherence by up to 70 +/- 1%. Single MAbs against CR1 or CR3 consistently inhibit adherence by 38-55%. In contrast, MAbs against other monocyte surface molecules, alone or in combination, do not significantly influence adherence. As studied by electron microscopy, 100% of monocyte-associated M. leprae are ingested in the presence of nonimmune serum and MAbs against CR3 markedly inhibit ingestion. Complement receptors CR1 and CR3 also mediate the low level of adherence observed in the absence of serum. Serum complement component C3 serves as a ligand on the bacterial surface in monocyte phagocytosis of M. leprae. Adherence of M. leprae to monocytes is enhanced by preopsonization (3.1 +/- 1.1-fold increase) and is markedly reduced in less than 0.5% fresh serum (66 +/- 7% reduction) or heat-inactivated serum (68 +/- 3% reduction). Adherence is also markedly reduced in C3- or factor B-depleted serum; repletion with purified C3 or factor B increases adherence 4.3 +/- 0.8- and 2.6 +/- 0.2-fold, respectively. C3 is fixed to M. leprae by the alternative pathway of complement activation, as determined by a whole bacterial cell ELISA. By electron microscopy, monocytes ingest M. leprae by conventional phagocytosis. This study demonstrates that (a) human monocyte complement receptors CR1 and CR3 mediate phagocytosis of M. leprae; (b) complement component C3 on the bacterial surface serves as a ligand for complement receptors; (c) complement component C3 binds to M. leprae by the alternative pathway of complement activation; and (d) monocytes phagocytize M. leprae by conventional phagocytosis.
Travelling-wave photodetectors (2002)

Attention to the microwave design of waveguide photodetectors leads to travelling-wave photodetectors. These devices show bandwidths as high as 172 GHz, the highest reported for a p-i-n photodetector, and bandwidth efficiency products as large as 76 GHz, the largest reported for any photodetector without gain. Direct comparisons with vertically illuminated and waveguide photodetectors confirm the advantages of travelling-wave photodetectors.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cough reflex sensitivity and airway inflammation in patients with chronic cough due to non‐acid gastro‐oesophageal reflux (2011)

Chronic cough due to non-acid reflux may be related to cough reflex hypersensitivity caused by neurogenic airway inflammation and mast cell activation, in which weakly acidic reflux is possibly a major factor.
[Transfer of endothelial nitric oxide synthase gene in the purpose of gene therapy for pulmonary arterial hypertension]. (1996)

Nitric oxide (NO) is a messenger molecule involved in diverse processes in many tissues. For example, NO is responsible for the bactericidal activities of macrophages, and in blood vessels it accounts for endothelium-derived relaxing factor activity. Recently, inhalation of NO gas was reported to improve the acute pulmonary arterial hypertension. Based on this knowledge, recombinant expression of endothelial nitric oxide synthase (eNOS) in lung may have profound effects on pulmonary vasomotor function and pulmonary arterial smooth muscle proliferation and platelet adhesion. On the basis of this concept, we evaluate the feasibility of gene therapy for chronic pulmonary arterial hypertension using hypoxia regulatable adenoviral vector coding eNOS cDNA.
SHORT REPORT: PILOTING PAPERLESS DATA ENTRY FOR CLINICAL RESEARCH IN AFRICA (2005)

Direct data entry, using handheld computers, may simplify and streamline data management, especially in remote settings. We compared the accuracy of data entry using the current standard practice (a paper-based case report form with double data entry) with that using a personal digital assistant (PDA) in a clinical study in rural Gabon. The rate of discrepant entries was 1.7%. Categorical data (presented in "pull down" menus on the PDA) were more commonly discrepant than were continuous "typed in" data (2.4% versus 1.2%; P = 0.001). Both systems functioned smoothly and no data were lost. The clinicians involved in this study preferred the handheld computers, and their use will be considered in future studies in an African clinical research network.
Deferoxamine Decreases Necrosis in Dorsally Based Pig Skin Flaps (1989)

Deferoxamine, a free radical scavenger and iron chelator, has been shown to improve skin flap survival in ischemic flap surgery in rats. The present study investigates the value of deferoxamine in ischemic flap surgery in the porcine model. Four 4 x 12 cm flaps, 3 cm apart and 3 cm from the dorsal midline, were elevated on each of six female pigs, weighing 50 to 60 pounds each. The animals were divided into two test groups. Group 1 received six 1 gm doses of deferoxamine in 4 ml of sterile water intramuscularly every 6 hours preoperatively for five doses, followed by the administration of 1 g every 6 hours for the first 6 days postoperatively. Group 2 received 4 ml of normal saline administered intramuscularly as above. The percentage of flap necrosis was assessed on postoperative day 7 by the weighing paper technique. Group 1 had 17.1% necrosis and group 2 had 33% necrosis (p less than 0.005). Deferoxamine has decreased flap necrosis in the porcine model and may be of use in augmenting the surviving length of flaps in human beings.
Completion of the KCC 378-H: A Case History (1992)

ABSTRACT A great deal has been published in recent years regarding horizontal well technology. However, little has been pub-lished concerning high rate acid stimulation treatments in openhole sections in horizontal wells. In fact, several articles suggest that a lateral section must be cemented and cased for the appropriate zonal isolation.1 This paper is a case history of a lateral openhole completion which utilized a high rate acid stimulation, polymer gel blocks for diversion, and dynamic spectral gamma ray log analysis. The Keystone Cattle Company Well No. 378-H, located in Winkler County, Texas was completed in the Wolfcamp Formation of the Flying "W" Field. The completion interval consisted of 1388 ft (423 m) of lateral, openhole section. A 200,000 gal (757 m3) multiple stage, foamed nitrogen acid stimulation was performed using polymer gel blocks for diversion. Five of the acid stages were tagged with three different radioactive isotopes. A spectral gamma ray log was used to identify the treatment intervals during the stimulation to effectively displace the polymer gel blocks. This paper includes background on the well and objectives for the completion techniques used. The detail procedure and evaluation of the real-time pressure and logging data are also discussed.
Chemosterilized Autolyzed Antigen-Extracted Allogeneic (AAA) Bone Matrix Gelatin for Repair of Defects from Excision of Benign Bone Tumors (1981)

In a series of 33 bone graft operations, antigen-extracted, autolyzed, allogeneic (AAA) bone matrix gelatin was substituted for autologous bone. The period of follow-up was 2.0 to 3.5 years. AAA bone gelatin was resorbed more rapidly than whole bone. AAA bone gelatin was replaced by new bone in the same intervals of time as observed with autologous bone. In treatment of bone tumors with AA bone gelatin, the results of the operation depend upon the nature of the pathologic processes in the host bed. In normal host bed, tight contact between implant and recipient bone is essential for success. The overall results of a preliminary study of 33 cases of 91% successful.
Angiotensin I converting enzyme inhibitors and cardiac remodeling. (1991)

Angiotensin I converting enzyme (ACE) inhibitors are widely used in the treatment of heart failure. It is not known whether the beneficial effects of ACE inhibition are only due to a reduction in pre- and afterload or whether ACE inhibition also has direct effects on cardiac remodeling processes after myocardial infarction. In addition, the effects of differential timing of the treatment are not known. The left coronary artery was ligated in rats to induce a myocardial infarction. Control rats received no treatment. Captopril was given via s.c. placed minipumps (500 micrograms/kg.h) in the first 3 weeks or in the third and fourth week after induction of the myocardial infarction. The structural changes of the heart were investigated. Early after ligation the left ventricle was dilated in association with a marked, but transient DNA synthesis in the remaining left ventricle; the amount of collagen also increased. Early captopril treatment blocked this response, while late treatment had no effects. We suggest that the negative effects of early captopril treatment are due to an interference with the normal adaptive responses of the heart to the loss of muscle, probably through interactions at the cellular level.
Role of the alpha v beta 3 integrin in human melanoma cell invasion. (1992)

The human melanoma cell line A375M expresses the vitronectin receptor (alpha v beta 3 integrin) on its cell surface. Treatment of A375M cells with either polyclonal or monoclonal anti-alpha v beta 3 antibodies resulted in stimulation of invasion through basement membrane matrices in vitro. Similar treatment of these cells with a monoclonal anti-alpha v antibody, which does not inhibit the adhesive function of the alpha v beta 3 antigen, also stimulated invasion; however, anti-beta 3 antibody treatment had no effect. Furthermore, pretreatment of the cells with vitronectin or addition of vitronectin to the basement membrane matrix also resulted in stimulation of invasion. Similar treatments with fibronectin receptor antibody or fibronectin had no effect on invasion. Analysis of type IV collagenase expression in cells treated with anti-alpha v beta 3 antibody showed higher levels of both the secreted 72-kDa enzyme and its mRNA. Signal transduction through the alpha v beta 3 integrin could underlie the elevated expression of metalloproteinase and the enhanced invasion of A375M cells through basement membrane matrices.
Quantitative impurity analysis of monoclonal antibody size heterogeneity by CE‐LIF: Example of development and validation through a quality‐by‐design framework (2012)

This paper describes the framework of quality by design applied to the development, optimization and validation of a sensitive capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) assay for monitoring impurities that potentially impact drug efficacy or patient safety produced in the manufacture of therapeutic MAb products. Drug substance or drug product samples are derivatized with fluorogenic 3-(2-furoyl)quinoline-2-carboxaldehyde and nucleophilic cyanide before separation by CE-SDS coupled to LIF detection. Three design-of-experiments enabled critical labeling parameters to meet method requirements for detecting minor impurities while building precision and robustness into the assay during development. The screening design predicted optimal conditions to control labeling artifacts while two full factorial designs demonstrated method robustness through control of temperature and cyanide parameters within the normal operating range. Subsequent validation according to the guidelines of the International Committee of Harmonization showed the CE-SDS/LIF assay was specific, accurate, and precise (RSD ≤ 0.8%) for relative peak distribution and linear (R > 0.997) between the range of 0.5-1.5 mg/mL with LOD and LOQ of 10 ng/mL and 35 ng/mL, respectively. Validation confirmed the system suitability criteria used as a level of control to ensure reliable method performance.
Partial Reduction of Nitriles to Aldehydes by Catecholalane (1,3,2-Benzodioxaluminole) (1996)

Catecholalane (1,3,2-Benzodioxaluminole, CA) reduced various aromatic and aliphatic nitriles to the corresponding aldehydes in very high yields at 25 °C.
Interferon beta in the treatment of multiple sclerosis (1998)

Interferon beta (IFN-beta) has been shown in several clinical trials to have efficacy in MS. Its mechanism of action, however, remains unclear. In this review, several biological activities of IFN-beta are highlighted, including its inhibitory effects on proliferation of leukocytes and antigen presentation. Furthermore, IFN-beta may modulate the profile of cytokine production toward that of the anti-inflammatory phenotype, and this appears to occur in the systemic circulation and within the CNS. Finally, IFN-beta can reduce T-cell migration by inhibiting the activity of T-cell matrix metalloproteinases. These activities are likely to act in concert to account for the mechanism of IFN-beta in MS.
A Genomic Approach to Identify Novel Progesterone Receptor Regulated Pathways in the Uterus during Implantation (2002)

The cellular actions of steroid hormone progesterone (P) are mediated via its nuclear receptors, which regulate the expression of specific target genes. The identity of gene networks that are regulated by the P receptors (PRs) in the uterus at various stages of the reproductive cycle and pregnancy, however, remain largely unknown. In this study, we have used oligonucleotide microarrays to identify mRNAs whose expression in the pregnant mouse uterus is modulated by RU486, a well-characterized PR antagonist, which is also an effective inhibitor of implantation. We found that, in response to RU486, expression of mRNAs corresponding to 78 known genes was down-regulated at least 2-fold in the preimplantation mouse uterus. The PR regulation of several of these genes was ascertained by administering P to ovariectomized wild-type and PR knockout (PRKO) mice. Detailed spatio-temporal analysis of these genes in the pregnant uterus indicated that their expression in the epithelium and stroma could be correlated with the expression of PR in those cell types. Furthermore, time-course studies suggested that many of these genes are likely primary targets of PR regulation. We also identified 70 known genes that were up-regulated at least 2-fold in the pregnant uterus in response to RU486. Interestingly, initial examination of a number of RU486-inducible genes reveals that their uterine expression is also regulated by estrogen. The identification of several novel PR-regulated gene pathways in the reproductive tract is an important step toward understanding how P regulates the physiological events leading to implantation.
Plasmon-controlled fluorescence: A new paradigm in fluorescence spectroscopy (2008)

Fluorescence spectroscopy is widely used in chemical and biological research. Until recently essentially all fluorescence experiments were performed in the far-field regime. By far-field we mean at least several wavelengths from the fluorophore. In recent years there has been a growing interest in the interactions of fluorophores with metallic surfaces or particles. Near-field interactions are those occurring within a wavelength distance of an excited fluorophore. The spectral properties of fluorophores can dramatically be altered by near-field interactions with the electron clouds present in metals. These interactions modify the emission in ways not seen in classical fluorescence experiments. Fluorophores in the excited state can create plasmons that radiate into the far-field and that fluorophores in the ground state can interact with and be excited by surface plasmons. These reciprocal interactions suggest that the novel optical absorption and scattering properties of metallic nanostructures can be used to control the decay rates, location, and direction of fluorophore emission. We refer to these phenomena as plasmon-controlled fluorescence (PCF). We will present a review of the recent work on metal-fluorophore interactions and suggest how these effects could result in new classes of experimental procedures, novel probes, bioassays and devices. While there are many complexities to fluorophore-metal interactions there are also many opportunities. In addition to control of the chemical structure of the fluorophore we can now control, to some extent, the processes of excitation and emission with nearby metallic nanostructures resulting in new approaches to high-throughput biology, diagnostics and molecular imaging.
Magnetically-oriented phospholipid micelles as a tool for the study of membrane-associated molecules (1994)

Introduction: Structure of Membrane-Associated Molecules by NMR High Resolution Solid State NMR Spectroscopy of Membrane Samples 2.1. Sampling spinning methods 2.2. Mechanical orientation of bilayers 2.3. Magnetic orientation of bilayers 2.3.1. Oriented phospholipid bilayers 2.3.2. Incorporation of membrane-associated molecules 2.3.3. Future development of magnetically orientable lipid media Experimental Considerations for Magnetically-Orientable Membrane Systems 3.1. Spectrometer requirements 3.2. Isotopic labeling 3.3. Strong coupling Anisotropic Spin Interactions: The Source of Orientation-Based Structural Data 4.1. Dipolar coupling 4.2. Quadrupolar coupling 4.3. Chemical shift anisotropy 4.4. Spin relaxation Determining Structure and Dynamics of Membrane-Bound Molecules 5.1. Structure and dynamics directly from experimental measurements 5.1.1. Order matrix analysis 5.1.2. Torsion angle analysis 5.2. NMR data as structural constraints in molecular modeling 5.3. Molecular dynamics simulations followed by back calculation of data Future Prospects Acknowledgements References 421 422 422 423 423 424 429 429 430 430 430 432 432 433 433 434 436 437 437 437 438 439 440 442
Molecular cloning and sequence analysis of the cyanobacterial gene for the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (1983)

Ribulose-1,5-bisphosphate carboxylase/oxygenase consists of large subunits (LS) and small subunits. In plants, the LS is encoded in chloroplast DNA and the small subunit, in nuclear DNA. In cyanobacteria, both subunits are thought to be encoded in chromosomal DNA because of prokaryotes. The gene for the LS of ribulose-1,5-bisphosphate carboxylase/oxygenase from a cyanobacterium, Anacystis nidulans 6301, has been cloned in pBR322 and subjected to sequence analysis. The coding region contains 1,416 base pairs (472 codons). The deduced amino acid sequence of A. nidulans LS protein shows 80% homology with sequences of maize, spinach, and tobacco LS proteins; the nucleotide sequence of A. nidulans LS gene shows 70% homology with sequences of the plant genes. Between A. nidulans LS and the plant LS proteins there is exact sequence homology around the lysine residue to which the activator CO(2) binds and around the two lysine residues to which ribulose 1,5-bisphosphate binds. The amino acid sequence where the LS binds to the small subunit is also highly conserved. From comparison of the LS proteins of A. nidulans and the three plants, the rate of amino acid substitution is estimated to be 0.25-0.5 x 10(-9) per year per site, which is far below the median value of various types of proteins (1.2 x 10(-9) for hemoglobin alpha). The LS protein is thus a conserved protein.
A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma (2005)

Denileukin diftitox, a genetically engineered fusion protein combining the enzymatically active domains of diphtheria toxin and the full-length sequence for interleukin-2 (IL-2), efficiently targets lymphoma cells expressing the high-affinity IL-2 receptor (IL-2R) consisting of the alpha/p55/CD25, beta/p75/CD122, and gamma/p64/CD132 chains. In vitro studies demonstrated that the retinoid X receptor (RXR) retinoid, bexarotene, at biologically relevant concentrations of 10(-6) M to 10(-8) M, upregulated both the p55 and p75 subunits of the IL-2R and enhanced 5- to 10-fold the susceptibility of T-cell leukemia cells to denileukin diftitox. To determine whether this biomodulatory effect could be recapitulated in vivo, we treated 14 patients with relapsed or refractory cutaneous T-cell lymphoma with escalating doses of bexarotene (75 mg/day-300 mg/day) and denileukin diftitox (18 mcg/kg per day x 3 days every 21 days) in a phase 1 trial. Overall response was 67% (4 complete responses, 4 partial responses). Modulation of IL-2R expression was observed at or above a bexarotene dose of 150 mg/day. Four patients experienced grade 2 or 3 leukopenia, and 2 had grade 4 lymphopenia. Our results demonstrate that the combination of denileukin diftitox and bexarotene is well tolerated and that even low doses (150 mg/day) of bexarotene are capable of in vivo upregulation of CD25 expression on circulating leukemia cells.
Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors (2003)

Binding specificity between fibroblast growth factors (FGFs) and their receptors (FGFRs) is essential for mammalian development and is regulated primarily by two alternatively spliced exons, IIIb ("b") and IIIc ("c"), that encode the second half of Ig-like domain 3 (D3) of FGFRs. FGF7 and FGF10 activate only the b isoform of FGFR2 (FGFR2b). Here, we report the crystal structure of the ligand-binding portion of FGFR2b bound to FGF10. Unique contacts between divergent regions in FGF10 and two b-specific loops in D3 reveal the structural basis by which alternative splicing provides FGF10-FGFR2b specificity. Structure-based mutagenesis of FGF10 confirms the importance of the observed contacts for FGF10 biological activity. Interestingly, FGF10 binding induces a previously unobserved rotation of receptor Ig domain 2 (D2) to introduce specific contacts with FGF10. Hence, both D2 and D3 of FGFR2b contribute to the exceptional specificity between FGF10 and FGFR2b. We propose that ligand-induced conformational change in FGFRs may also play an important role in determining specificity for other FGF-FGFR complexes.
Potential Applications of Enzymes in Waste Treatment (1997)

The implementation of increasingly stringent standards for the discharge of wastes into the environment has necessitated the need for the development of alternative waste treatment processes. A review of research directed toward developing enzymatic treatment systems for solid, liquid and hazardous wastes is presented. A large number of enzymes from a variety of different plants and microorganisms have been reported to play an important role in an array of waste treatment applications. Enzymes can act on specific recalcitrant pollutants to remove them by precipitation or transformation to other products. They also can change the characteristics of a given waste to render it more amenable to treatment or aid in converting waste material to value-added products. Before the full potential of enzymes may be realized, it is recommended that a number of issues be addressed in future research endeavors including the identification and characterization of reaction by-products, the disposal of reaction products and reduction of the cost of enzymatic treatment. © 1997 SCI.