gebhart/patrepeval huggingface dataset:
Pharmacokinetics of amoxapine and its active metabolites. (1985)

The plasma concentrations of amoxapine and its active metabolites, 8-hydroxyamoxapine and 7-hydroxyamoxapine were determined in 8 healthy volunteers receiving a single oral dose of 100 mg of the drug. Considerable interindividual variation was seen in the plasma levels of the three substances. Amoxapine reached maximum levels of 67.4 +/- 35.8 ng/ml between 1 and 2 h after administration. The decline of amoxapine levels in plasma was biphasic. The mean elimination half-life was 9.8 +/- 2.6 h and the estimated first-pass loss ranged between 0.18 and 0.54. The peak levels of the metabolites were reached between 1 and 3 h after administration, with 8-hydroxyamoxapine levels significantly higher than those of 7-hydroxyamoxapine. The mean elimination half-lives were 30.8 and 5.1 h for 8-hydroxyamoxapine and 7-hydroxyamoxapine respectively. The margins of the plasma concentrations reached at steady-state were calculated according to pharmacokinetics parameters for a dosage interval of 8 h.
Cervical Interbody Xenograft With Plate Fixation (1996)

Interbody xenograft combined with a rigid plate fixation avoids the problems linked to autologous or allogenous bone graft and gives a safe and solid interbody fusion when arthrodesis is required in ligamentous instability of the cervical spine.
The effect of CaO sintering on cyclic CO2 capture in energy systems (2007)

Abstract The importance of calcium‐based sorbents, especially natural limestones, for CO 2 removal necessitates an investigation into the sorbent decay mechanism. This study starts from pore size distributions for samples from tests under various calcination/carbonation cycling conditions. A sintering model is formulated to describe the cyclic behavior of sorbents during cyclic calcination and carbonation. It explains the similar reversibility shown by sorbents under different test conditions. A balance between shorter cumulative sintering time and higher calcination rates appears to be responsible for the similar degrees of sintering and sorbent reversibility. © 2007 American Institute of Chemical Engineers AIChE J, 2007
NOX5 in Human Spermatozoa (2012)

Physiological and pathological processes in spermatozoa involve the production of reactive oxygen species (ROS), but the identity of the ROS-producing enzyme system(s) remains a matter of speculation. We provide the first evidence that NOX5 NADPH oxidase is expressed and functions in human spermatozoa. Immunofluorescence microscopy detected NOX5 protein in both the flagella/neck region and the acrosome. Functionally, spermatozoa exposed to calcium ionophore, phorbol ester, or H(2)O(2) exhibited superoxide anion production, which was blocked by addition of superoxide dismutase, a Ca(2+) chelator, or inhibitors of either flavoprotein oxidases (diphenylene iododonium) or NOX enzymes (GKT136901). Consistent with our previous overexpression studies, we found that H(2)O(2)-induced superoxide production by primary sperm cells was mediated by the non-receptor tyrosine kinase c-Abl. Moreover, the H(V)1 proton channel, which was recently implicated in spermatozoa motility, was required for optimal superoxide production by spermatozoa. Immunoprecipitation experiments suggested an interaction among NOX5, c-Abl, and H(V)1. H(2)O(2) treatment increased the proportion of motile sperm in a NOX5-dependent manner. Statistical analyses showed a pH-dependent correlation between superoxide production and enhanced sperm motility. Collectively, our findings show that NOX5 is a major source of ROS in human spermatozoa and indicate a role for NOX5-dependent ROS generation in human spermatozoa motility.
B‐cell malignancies as a model for cancer vaccines: from prototype protein to next generation genetic chemokine fusions (1999)

B-cell malignancy-derived Ig may be considered a model tumor antigen for vaccine development. However, as a non-immunogenic self antigen, it must also be first rendered immunogenic by chemical or genetic fusion to carriers which enable the induction of protective antitumor immunity in murine tumor models. Our group has demonstrated that active immunizations of human patients with idiotypic vaccines elicited antigen-specific CD8+ T-cell responses and antitumor effects. Several alternative preclinical strategies to develop vaccines have been previously reported, including fusion of tumor idiotype-derived single chain Fv with cytokines and immunogenic peptides. On the other hand, we have recently explored a different approach in which the model antigen is rendered immunogenic in mice by genetically fusing it to a chemokine moiety. Administration of these vaccines as fusion proteins or naked DNA vaccines may allow efficient targeting of antigen-presenting cells in vivo. Potent antitumor immunity was dependent on the generation of specific anti-idiotypic antibodies and both CD4+ and CD8+ effector T cells. We propose that chemokine fusion may represent a novel, general strategy for formulating existing or newly identified tumor and HIV antigens into vaccines for cancer and AIDS, respectively, which elicit potent CD8+ T-cell immunity.
Fetal DNA Quantitation in Peripheral Blood Is Not Useful as a Marker of Disease Severity in Women with Preeclampsia (2003)

Fetal trafficking is more likely to be detected in women with preeclampsia compared to control women but the quantity does not appear to correlate with disease severity.
Transgenic MUC1 Interacts with Epidermal Growth Factor Receptor and Correlates with Mitogen-activated Protein Kinase Activation in the Mouse Mammary Gland (2001)

MUC1 is a large (>400 kDa), heavily glycosylated transmembrane protein that is aberrantly expressed on greater than 90% of human breast carcinomas and subsequent metastases. The precise function of MUC1 overexpression in tumorigenesis is unknown, although various domains of MUC1 have been implicated in cell adhesion, cell signaling, and immunoregulation. Stimulation of the MDA-MB-468 breast cancer line as well as mouse mammary glands with epidermal growth factor results in the co-immunoprecipitation of MUC1 with a tyrosine-phosphorylated protein of approximately 180 kDa. We have generated transgenic lines overexpressing full-length (MMF), cytoplasmic tail deleted (DeltaCT), or tandem repeat deleted (DeltaTR)-human MUC1 under the control of the mouse mammary tumor virus promoter to further examine the role of MUC1 in signaling and tumorigenesis. Immunoprecipitation experiments revealed that full-length transgenic MUC1 physically associates with all four erbB receptors, and co-localizes with erbB1 in the lactating gland. Furthermore, we detected a sharp increase in ERK1/2 activation in MUC1 transgenic mammary glands compared with Muc1 null and wild-type animals. These results point to a novel function of increased MUC1 expression, potentiation of erbB signaling through the activation of mitogenic MAP kinase pathways.
Formulation of controlled-release delivery systems for the alpha-melanocyte stimulating hormone analog, Melanotan-I (1997)

The overall objective of this research was to develop controlled-release formulations of Melanotan-I (MT-I). Two polymers were used, Poloxamer 407 (P407) and Poly(D,L lactide-co-glycolide) (PLGA). First, various aqueous formulations of P407 were evaluated containing MT-I and 25% w/v P407 alone, or with one of the following additives present, i.e., polyvinylpyrrolidone, methylcellulose or hydroxypropyl methylcellulose. The in-vitro release profiles of MT-I from the P407 formulations and the dissolution of the gel were obtained simultaneously using a membraneless in vitro model and a zero-order profile was observed for both. The in-vivo release kinetics of selected formulations were analyzed in guinea pigs following intraperitoneal administration. The plasma concentration-time profiles showed an extended release of the peptide formulated with gel compared to the interperitoneal administration of MT-I in solution and exhibited potential for prolonged release up to 24 hrs only. Biodegradable implants of PLGA copolymer were prepared by a melt-extrusion method. The in vitro release of MT-I from the implants exhibited a triphasic profile with an initial rapid release followed by a secondary phase of slow release, then a tertiary phase of rapid release due to erosion of the polymer. Based on release kinetics of MT-I from different viscosity PLGA implants, the polymer having a viscosity of 0.6 dL/gm was selected for preparing an implant system with a one-month duration of release. Molecular weight reduction, mass loss and lactic acid release from PLGA implants were characterized in order to correlate the in vitro release profile of MT-I with hydrolytic degradation of the polymer. The in vivo release profile of the MT-I depot implanted subcutaneously exhibited a one-month release of the peptide and the reflectance reading obtained from a reflectometer showed a prolonged skin darkening for 3 months. A 2.5 fold increase in the melanin pigment (eumelanin) was observed in guinea pig skin biopsy samples. The results indicate that the PLGA implants are a promising delivery device for controlled-release of MT-I over a one-month period.
Requirements and Technology for Computer Security (1991)

This document is a draft of chapters 2 and 3 of Computers at Risk, the National Academy of Science’s report on computer security, along with the technical appendix, references, and glossary. Section 1 describes requirements for security, and section 2 the technology available for meeting them. Section 3 contains more technical detail on a number of specific topics. There is a list of references and a glossary at the end.
Like Fire in Dry Stubble - The Stone Movement 1804-1832 (Part 1) (1963)

Roberts, J W. and Roberts, R. L. Jr. (1963) "Like Fire in Dry Stubble - The Stone Movement 1804-1832 (Part 1)," Restoration Quarterly: Vol. 7 : No. 3. This repository hosts selected Restoration Quarterly articles in downloadable PDF format. For the benefit of users who would like to browse the contents of RQ, we have included all issue covers even when full-text articles from that issue are unavailable. All Restoration Quarterly articles are available in full text in the ATLA Religion Database, available through most university and theological libraries or through your local library’s inter-library loan service.
Programmable arithmetic devices for high speed digital signal processing (1992)

The high throughput computation requirements of real-time digital signal processing (dsp) systems usually dictate hardware intensive solutions. Often attendant to hardware approaches are problems of high development costs, slow turnaround, susceptibility to errors, and difficulty in testing and debugging, all of which tend to inhibit the rapid implementation of such systems. Research is underway into the synthesis of application specific hardware to aid the system designer by automatically generating hardware that is &amp;quot;correct by construction&amp;quot;. The creation of configurable, pre-fabricated hardware that has been designed for high speed computations forms part of this research and is the main topic of this thesis. This work contains a survey of some typical real-time dsp algorithms drawn from video and speech processing and summarizes the particular computation challenges posed by this class of algorithms. Currently available hardware choices and their trade-offs and limitations are discu...
ChemInform Abstract: FACILE PREPARATION OF THE INDIVIDUAL DIASTEREOISOMERS OF THYMIDINE 3′,5′‐CYCLIC PHOSPHOROTHIOATE (CTMPS) (1981)

Abstract Aus Thymidin (I) und Tris‐dimethylamino‐phosphin (II) erhält man nach Methanol‐Zugabe die stereoisomeren cyclischen Phosphite (III), die mit Bis‐tert.‐butyl‐disulfid (IV) zu den isomeren Thiophosphaten (V) und (VI) führen.
Aerosolized fluorescent microspheres detected in the lung using confocal scanning laser microscopy (1993)

Aerosolized fluorescent microspheres were used to study particle deposition in site-specific regions of the lung with confocal laser scanning microscopy. A nebulizer was used to aerosolize microspheres followed by passage through a heated discharging column to reduce static charge and to remove water surrounding each microsphere. Precoating of microspheres with albumin helped to minimize displacement during vascular fixation of the lungs. Confocal laser microscopy facilitated visualization of microspheres throughout the bronchial tree, ducts, and alveoli of the lungs. The use of fluorescent microspheres and confocal laser imaging provided distinct advantages compared with other methods to study lung particle deposition due to (1) the generation of single microspheres of uniform size by nebulization, (2) easy detection of microspheres in large slabs of microdissected lung tissues, (3) excellent resolution of tissue surfaces and microspheres for an infinite number of orientations and planes of section, and (4) the ability to visualize microspheres below fluid lining layers and on surfaces that could not easily be done by other methods of microscopy.
A METHOD FOR PRODUCING SPECIFIC ANTISERA WITH SMALL DOSES OF IMMUNOGEN (1971)

We have succeeded in producing specific antisera to the subunits of HCG and testosterone conjugates with one immunization of 20 to 100 μg of immunogen. The potential of the method for producing specific antisera to glycoprotein and other hormones with limited amounts of purified material prompts this report. CR 100α and CR 100β, the subunits of HCG,. were prepared by Drs. R. E. Canfield and F. Morgan (1). Testosterone-3-(0-carboxymethy1) oxime was coupled to either bovine serum albumin (Armour) or keyhole limpet hemocyanin (Calbiochem) (2). Equal volumes of complete Freund's adjuvant, a 0.15 M NaCl solution of the immunogen and dried tubercle bacilli (2.5 mg/ml of total mixture) were homogenized for 5–10 minutes at increasing speeds to maximum setting in a Sorvall Omnimixer. Fur was shaved from the back and proximal limbs of 3 month old New Zealand white rabbits and the emulsion administered intradermally at 30–50 sites so that each animal received a total of 2 ml of the emulsion. At a separate site 0.5 ml of crude Bordetella pertussis vaccine (E. Lilly Corp.) was injected intradermally.
Large-volume leukapheresis in pediatric patients: pre-apheresis peripheral blood CD34+ cell count predicts progenitor cell yield. (1999)

Our results suggest that the number of CD34+ cells harvested in a single large-volume leukapheresis can be predicted from the measurement of peripheral blood CD34+ cell concentration on the collection day.
Molecular Analysis of Ligand Binding to the Second Cluster of Complement-type Repeats of the Low Density Lipoprotein Receptor-related Protein (1997)

The low density lipoprotein receptor-related protein (LRP), a member of the low density lipoprotein receptor gene family, mediates the cellular uptake of a diversity of ligands. A folding chaperone, the 39-kDa receptor-associated protein (RAP) that resides in the early compartments of the secretory pathway inhibits the binding of all ligands to the receptor and may serve to prevent premature binding of ligands to the receptor during the trafficking to the cell surface. To elucidate the molecular interactions that underlie the interplay between the receptor, RAP, and the ligands, we have analyzed and delineated the binding sites of plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (t-PA).PAI-1 complexes, RAP, and the anti-LRP Fab fragment Fab A8. To that end, we have generated a series of soluble recombinant fragments spanning the second cluster of complement-type repeats (C3-C10) and the amino-terminal flanking epidermal growth factor repeat (E4) of LRP (E4-C10; amino acids 787-1165). All fragments were expressed by stably transfected baby hamster kidney cells and purified by affinity chromatography. A detailed study of ligand binding to the fragments using surface plasmon resonance revealed the presence of three distinct, Ca2+-dependent ligand binding sites in the cluster II domain (Cl-II) of LRP. t-PA.PAI-1 complexes as well as PAI-1 bind to a domain located in the amino-terminal portion of Cl-II, spanning repeats E4-C3-C7. Adjacent to this site and partially overlapping is a high affinity RAP-binding site located on repeats C5-C7. Fab A8, a pseudo-ligand of the receptor, binds to a third Ca2+-dependent binding site on repeats C8-C10 at the carboxyl-terminal end of Cl-II. Next, we studied the RAP-mediated inhibition of ligand binding to LRP and to Cl-II. As expected, we observed a strong inhibition of t-PA.PAI-1 complex and Fab A8 binding to LRP by RAP (IC50 congruent with 0.3 nM), whereas in the reverse experiment, competition of t-PA. PAI-1 complexes and Fab A8 for RAP binding to LRP could only be shown at high concentrations of competitors (>/=1 microM). Interestingly, even though the equilibrium dissociation constants for the binding of RAP to LRP and to Cl-II are similar, the binding of the ligands to Cl-II is only prevented by RAP at concentrations that are at least 2 orders of magnitude higher than those required for inhibition of ligand binding to LRP. Our results favor models that propose RAP-induced allosteric inhibition of ligand binding to LRP that may require LRP moieties that are located outside Cl-II of the receptor.
Nerve Growth Factor-Inducing Activity of Hericium erinaceus in 1321N1 Human Astrocytoma Cells (2008)

Neurotrophic factors are essential to maintain and organize neurons functionally; thereby neurotrophic factor-like substances or their inducers are expected to be applied to the treatment of neurodegenerative diseases such as Alzheimer's disease. In the present study, we firstly examined the effects of ethanol extracts of four edible mushrooms, Hericium erinaceus (Yamabushitake), Pleurotus eryngii (Eringi), Grifola frondosa (Maitake), and Agaricus blazei (Himematsutake), on nerve growth factor (NGF) gene expression in 1321N1 human astrocytoma cells. Among the four mushroom extracts, only H. erinaceus extract promoted NGF mRNA expression in a concentration-dependent manner. In addition, secretion of NGF protein from 1321N1 cells was enhanced by H. erinaceus extracts, and the conditioned medium of 1321N1 cells incubated with H. erinaceus extract enhanced the neurite outgrowth of PC12 cells. However, hericenones C, D and E, constituents of H. erinaceus, failed to promote NGF gene expression in 1321N1 cells. The enhancement of NGF gene expression by H. erinaceus extracts was inhibited by the c-jun N-terminal kinase (JNK) inhibitor SP600125. In addition, H. erinaceus extracts induced phosphorylation of JNK and its downstream substrate c-Jun, and increased c-fos expression, suggesting that H. erinaceus promotes NGF gene expression via JNK signaling. Furthermore we examined the efficacy of H. erinaceus in vivo. ddY mice given feed containing 5% H. erinaceus dry powder for 7 d showed an increase in the level of NGF mRNA expression in the hippocampus. In conclusion, H. erinaceus contains active compounds that stimulate NGF synthesis via activation of the JNK pathway; these compounds are not hericenones.
Functional ambivalence of the Kp43 (CD94) NK cell-associated surface antigen. (1995)

We originally characterized the Kp43 (CD94) surface Ag, whose expression is restricted to human NK cells and a minor T lymphocyte subset. As shown in the present study, anti-Kp43 mAbs but not their F(ab')2 fragments markedly inhibited the cytolytic activity of polyclonal-activated NK cells in a redirected lysis assay against the murine P815 cell line. Furthermore, anti-Kp43 mAbs also down-regulated the CD16-dependent redirected killing and PHA-induced lectin-dependent cellular cytotoxicity. However, the intensity of the inhibitory effect was variable and no significant down-regulation of cytotoxicity was substantiated in NK cell populations from some individuals. A similar variability in the responsiveness to anti-Kp43 mAb was noticed when fresh CD3- lymphocyte populations were tested: in some donors we observed the induction of redirected lysis, whereas in other samples the Kp43-specific mAb inhibited cytotoxicity. The analysis of single cell-derived microcultures provided a clue to interpret the variable responsiveness of polyclonal cell populations; remarkably, the cytolytic activity of some NK clones was inhibited, whereas that of others was either stimulated or unaffected. The pattern of responsiveness in the cytolytic assay correlated with TNF production upon stimulation with solid phase-bound anti-Kp43 mAbs. The different types of clones could be derived from the same individual, although their relative proportions varied from donor to donor. Moreover, Kp43 appeared to be coupled differently to signal transduction pathways, because (Ca2+)i mobilization in the presence of the Kp43-specific mAbs was substantiated only in clones that were activated in the redirected lysis assay.
Should Asthma Management Include Sojourns at High Altitude? (2005)

Sojourns in the high mountains have been recommended by specialists for patients with asthma since many decades. An inquiry among physicians of the 'Davoser Arzteverein' revealed as early as 1906 that 133/143 patients with bronchial asthma had no or only few asthma attacks during their stay in Davos, and that 81% had a persistent improvement of their disease. These early observations about effects of the alpine climate were, of course, reported at a time, when the spectrum of pharmacotherapy was very limited. However, these observations were consistent and were therefore regarded as proof for the therapeutic value of sojourns under alpine conditions in bronchial asthma. In recent years, however, the indication for asthma treatment in high mountains is increasingly questioned, in particular by health insurance systems. Therefore it is the aim of this contribution to summarize the available data about the effects of a stay of asthmatic patients at 1,500-1,800 m above sea level. It is concluded that the available evidence suggests a significant beneficial effect of high altitude in bronchial asthma, in particular in steroid-dependent patients.
Small RNA-divalent domains. (1996)

From a potentially completely sampled set of randomized 23-mer sequences, we selected RNAs that bind a Zn-column and also show KD approximately 100-400 microM for free Zn2+, probably relying on one or two direct ion coordinations. Comparison of selected sequences with previously known divalent sites suggests three or four small RNA motifs repeatedly found to interact with divalent ions. We suggest that the GC cluster, the augmented GC cluster, and the E element may be useful generalized ion-binding structures. Such structures may help identify similar divalent sites in sequenced RNAs and serve as substructures for design of functional RNA metallodomains.