gebhart/patrepeval huggingface dataset:
Liver-Directed Gene Transfer in Non-Human Primates (1997)

To develop a primate model for liver-directed gene therapy, we studied several gene transfer vehicles and routes in eight rhesus monkeys (Macaca mulatta). For this purpose, we used first-generation, replication-deficient adenoviral vectors carrying the Escherichia coli lacZ gene (Ad.CMVlacZ) or a lacZ-containing plasmid (pCMV beta) with lipofectamine for transfection. The reporter gene construct was infused into either the portal vasculature, common bile duct, or saphenous vein. Adenovirus-mediated gene transfer via the portal vein resulted in expression of lacZ in over 70% of hepatocytes by days 3-7, but was accompanied by acute hepatitis. Adenovirus-mediated gene transfer via the common bile duct resulted in lacZ expression in less than 10% of hepatocytes and was accompanied by portal inflammation. The animals mounted a significant immune response, as demonstrated by adenoviral antigen-induced T-cell proliferation and production of neutralizing anti-adenovirus antibodies and antibodies to E. coli beta-galactosidase (beta-Gal). Activation of the immune response was associated with rapid decrease of the reporter gene by days 13-21. Lipofectamine-mediated gene transfer was inefficient, and no lacZ expression in the liver was detected. To limit the host immune response, 4 animals were immunosuppressed by cyclophosphamide/prednisone and then infused with the Ad.CMVlacZ via the portal vein or the saphenous vein. The monkeys showed sustained expression of lacZ for up to 35 days with no evidence of inflammation. The primates transduced via the saphenous vein showed a level of beta-Gal expression in the liver similar to that of the portal vein-infused animals. In conclusion, adenovirus-mediated gene transfer to non-human primate livers via the portal vein or saphenous vein is efficient, but it results in transient expression and is accompanied by an immune response to both vector and transgene products and acute hepatitis, whereas lipofectamine-mediated transfer is inefficient. Manipulation of the host immune response may expand potential applications of adenoviral vectors for liver-directed gene transfer.
Streptokinase Stability Pattern during Storage in Various Solvents and at Different Temperatures (1975)

The activity drop of 5 u streptiokinasewas measured in 1 ml each of various solutions (9.9% NaCl solution, 5% glucose solution, 5% levulose solution, 10% dextran solution, gelatin solution, 3% albumin solution, michaelis buffer, glucose (5%)-heparin (750 u/ml) solution) at different incubation temperatures (-20 degrees C, 4 DEGREES C, 20 DEGREES C, 37 DEGREES C), and over different observations periods (15 min, 30 min, 45 min, 60 min, 6 h, 12 h, 24 h, and 48 h). Solution media tested for streptodinase-protecting quality were broken down into three groups. Group I: Solvents displaying excellent stabilizing properties gelatin and albumin solutions). Group II: Solvents displaying medium stabilizing properties (dextran and levulose solutions). Group III: Solvents displaying poor stabilizing properties (NaCl and glucose solutions, Michaelis buffer). In testing streptokinase concentrations as used for therapeutic purposes (1500 u/ml, 50,000 u/ml), no decay was found to take place over observation periods of up to 48 h, and no invluence by different solvents (Group I. II or III) was traceable. Heparin stored with streptokinase at room temperature over a period of 48 h did not alteranisms concerning the stability pattern of striptokinase are discussed. It appears that low streptokinase concentrations need negatively chargedcolloids to keep the protein structure intact. The streptokinase-protecting macro-molecules tested so far were albumin, gelatin, and streptokinase. Obviously, streptokinase by itself was able to preserve its own stability provided its concentration was of a certain order magnitude (1500 u/ml, 50,000 u/ml) .
International strategic minerals inventory summary report; niobium (columbium) and tantalum (1993)

Earth-science and mineral-resource agencies from several countries started the International Strategic Minerals Inventory in order to
Anti-epidermal growth factor receptor monoclonal antibodies in cancer therapy (2009)

The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor involved in the proliferation and survival of cancer cells. EGFR is the first molecular target against which monoclonal antibodies (mAb) have been developed for cancer therapy. Here we review the mechanisms underlying the effects of EGFR-specific mAb in cancer therapy. The efficacy of EGFR-specific mAb in cancer occurs thanks to inhibition of EGFR-generated signalling; furthermore, the effects of antibodies on the immune system seem to play an important role in determining the overall anti-tumour response. In this review, attention is focused on cetuximab and panitumumab, two mAb introduced recently into clinical practice for treatment of metastatic colorectal and head and neck cancer which target the external part of EGFR.
New Strategies in Polypeptide and Antibody Synthesis: An Overview (2004)

The synthesis of radioligands can benefit considerably from optimized recombinant protein production, both on the aspect of economy of production and on the level of improving the targeting and pharmacokinetics of the ligand. This paper first describes a general production optimization strategy, and then elaborates on a protein design strategy tailored to targeting applications. Production in Escherichia coli will benefit from economy of goods and time as compared to other organisms. In order to increase the chance of finding a successful production system in this host, we have assembled a large number of expression strategies in a single, uniform expression system (FastScreen). The system allows rapid optimization of direct production of native proteins or via a fusion protein strategy with subsequent recovery of the desired protein. As an example of recombinant radioligand synthesis for improved targeting and clearing, a manifold of intermediate molecular size was synthesized by fusing one Fab and two single-chain variable fragments (scFv) antibody binding fragments into a trifunctional molecule (Tribody). Due to the use of the specific heterodimerization of the Fab chains, trispecific, bispecific, or trivalent antibody derived targeting reagents can easily be obtained. Recombinant production techniques also allow for specific incorporation of amino acids favoring a site specific labeling (labeling tags).
Apolipoprotein B retention in the grossly normal and atherosclerotic human aorta. (1977)

Apoliporotein B (apoB) was measured in buffer-extracted homogenates of grossly normal and artherosclerotic human aortic intima by means of an electroimmunoassay procedure. The apoB values which were expressed as microgram per mg tissue dry weight, varied widely, ranging from 0.34 to 18.45 in normal intima and from 0.8 to 12.5 in fatty fibrous plaques. No consistent differences in apoB content were found between normal intimas from thoracic and abdominal aortic regions. There was a statistically significant positive correlation between the quantity of buffer-extractable apoB in normal regions and the plasma cholesterol and triglyceride concentration. Buffer-extractable apoB values were significantly higher in fatty fibrous plaques than in ulcerated lesions from the same vessel. However, fatty fibrous plaque apoB values were significantly lower than those from grossly normal regions from the same aorta, although the topographical distribution of apoB was more widespread in plaques than in normal regions, as shown by immunofluorescence studies. This apparent discrepancy reflected the incomplete extraction of apoB from plaques as contrasted to normal regions. The relatively loosely bound apoB, extractable by standard buffers, may represent intact low density lipoprotein (LDL) and/or very low density lipoprotein (VLDL), while the tightly bound fraction may represent insoluble complexes of intact lipoproteins within the plaque or delipidated apoB.
Design and Synthesis of Novel Isoquinoline-3-nitriles as Orally Bioavailable Kv1.5 Antagonists for the Treatment of Atrial Fibrillation (2006)

Novel 3-cyanoisoquinoline Kv1.5 antagonists have been prepared and evaluated in in vitro and in vivo assays for inhibition of the Kv1.5 potassium channel and its associated cardiac potassium current, IKur. Structural modifications of isoquinolinone lead 1 afforded compounds with excellent potency, selectivity, and oral bioavailability.
Importance of Neonatal FcR in Regulating the Serum Half-Life of Therapeutic Proteins Containing the Fc Domain of Human IgG1: A Comparative Study of the Affinity of Monoclonal Antibodies and Fc-Fusion Proteins to Human Neonatal FcR (2010)

The neonatal FcR (FcRn) binds to the Fc domain of IgG at acidic pH in the endosome and protects IgG from degradation, thereby contributing to the long serum half-life of IgG. To date, more than 20 mAb products and 5 Fc-fusion protein products have received marketing authorization approval in the United States, the European Union, or Japan. Many of these therapeutic proteins have the Fc domain of human IgG1; however, the serum half-lives differ in each protein. To elucidate the role of FcRn in the pharmacokinetics of Fc domain-containing therapeutic proteins, we evaluated the affinity of the clinically used human, humanized, chimeric, or mouse mAbs and Fc-fusion proteins to recombinant human FcRn by surface plasmon resonance analysis. The affinities of these therapeutic proteins to FcRn were found to be closely correlated with the serum half-lives reported from clinical studies, suggesting the important role of FcRn in regulating their serum half-lives. The relatively short serum half-life of Fc-fusion proteins was thought to arise from the low affinity to FcRn. The existence of some mAbs having high affinity to FcRn and a short serum half-life, however, suggested the involvement of other critical factor(s) in determining the serum half-life of such Abs. We further investigated the reason for the relatively low affinity of Fc-fusion proteins to FcRn and suggested the possibility that the receptor domain of Fc-fusion protein influences the structural environment of the FcRn binding region but not of the FcgammaRI binding region of the Fc domain.
Music Representation Issues, Techniques, and Systems (1993)

Music offers a challenging array of representation problems. As an art form, is distinguished by the presence of many relationships that can be treated mathematically, including rhythm and harmony. There are also many nonmathematical elements such as tension, expectancy, and emotion. Music can contain symbolic or structural relationships existing within and between the dimensions of pitch, time, timbre, harmony, tempo, rhythm, phrasing, and articulation. A further source of complexity is that music can mean printed notation, performance (instrument control) information, or resulting sounds. Finally, evolves with every new composition. There can be no true representation just as there can be no closed definition of music. These elements combine to make representation a rich field of study. Computers allow (and require) a formal approach to the study of representation. Computer programs demand that every detail of a representation be precisely specified, and the resulting precision allows experimentation and testing of new representations. The knowledge we gain from these experiments is useful in theory and in understanding by computer. Computers also allow the representation of dynamic, responsive, or interactive compositions, a concept that was hard to imagine before computing. Better representations also lead to more powerful human-computer interfaces and tools. This is an overview of some of the issues and techniques that arise in studies of representation. No attempt has been made to be exhaustive, so the reader is referred to the references and the other articles in this issue of Computer Music Journal for more information. In particular, I will omit any discussion of audio representations and transforms used in signal processing (see De Poll, Piccialli, and Roads, 1991), although this is an important part of representation. Levels of Representation
Potentiation of vincristine and Adriamycin effects in human hemopoietic tumor cell lines by calcium antagonists and calmodulin inhibitors. (1983)

verapamil, a calcium-influx blocker, enhanced the cytotoxicity of vincristine (VCR) in vitro 6- to 12-fold in eight human hemopoietic tumor cell lines established from acute lymphatic leukemia, acute myelogenous leukemia, and Burkitt's lymphoma. Great enhancement of VCR cytotoxicity was obtained in a VCR-resistant subline of K562 myelogenous leukemia. A maximum of approximate 100-fold increase in VCR cytotoxicity occurred. Heterogeneity in VCR sensitivity (80-fold difference in sensitivity) was observed in vitro among these human tumor cells. BALL and Daudi cells of B-cell type were more susceptible to VCR. At 6.6 or 20 microM of verapamil, the values for the concentration of drug required for 50% inhibition of cell growth for each cell line fell into a rather narrow range, and heterogeneity in VCR sensitivity among cell lines was circumvented in vitro. Verapamil also enhanced the cytotoxicity of Adriamycin, although the extent of enhancement was considerably small. Enhancement of VCR cytotoxicity also occurred with other calcium antagonists and calmodulin inhibitors. At maximum effective concentration of these reagents, a 3- to 5-fold increase in VCR cytotoxicity occurred in K562 cells. In VCR-resistant K562 cells, a more prominent enhancement (20- to 45-fold) was observed with these reagents. VCR resistance was circumvented in vitro. The mechanism of enhancement of VCR cytotoxicity was explained by the enhanced accumulation of VCR in K562, especially in resistant cells.
A high precision 3D object reconstruction method using a color coded grid and NURBS (1999)

A high-precision technique for reconstructing three-dimensional (3D) objects from its one-camera 2D views and using a color-coded structured light is described. The method does not require any a-priori knowledge of the absolute positioning and orientation of the camera, nor of a point in the scene. However a calibration process precedes the 3D reconstruction algorithm leading to a high-precision calculation of the position of the camera. The structured light, which is pseudo-randomly color-encoded, is used to determine unique points and lines on the surface of the object. The lines once extracted from a view of the object, are used for the determination of non-uniform rational Bezier splines (NURBS) curves to generate the surface of the object. The precision of the technique depends on the adaptation of the sampling rate of the structured light to the surface of the object. In a recent test, the precision of 7 tau (thousands of an inch) was achieved with a relatively smooth object. The paper describes only the 3D reconstruction process and not the integration of multiple views into one single 3D image of the object.
Targeting of Peptide and Protein Drugs to Specific Sites in the Oral Route (1995)

Although the distal small intestine has less lumenal and apical proteolytic activities, it has high activities of some apical peptidases. Colonic proteolytic activities are substantial, but their nature is less understood. The small intestine has di- and tripeptide transporter, facilitating absorption, and P-glycoprotein, an efflux pump suggested to limit absorption of small peptides. Several peptide and nonpeptide drugs have higher absorption in the ileum; however, enhancement on their absorption by enhancers varies from site to site. Specific delivery systems can target drugs to the distal intestine utilizing distinct regional pHs and specific microbial enzymes, but the key is how to achieve a reliable release.
Collective oscillations in a single-wall carbon nanotube excited by fast electrons (2001)

Electron energy loss spectroscopy is a well adapted tool for the investigation of the valence excitations of individual nanometer-size particles. The interpretation of the loss spectra of such small particles, however, relies in most cases on a quantitative comparison with simulated excitation probabilities. Here we present a formalism developed for the interpretation of the energy loss data of single-wall carbon nanotubes based on the hydrodynamic theory of plasmon excitations by high-energy electrons. The nanotubes are modeled as a two-dimensional electron gas confined on the circumference of a cylinder. The plasmon excitation probabilities, directly comparable to measurements, are discussed for various parameters.
Caspase-3-mediated Cleavage of Protein Kinase C θ in Induction of Apoptosis (1997)

Protein kinase C theta (PKCtheta) is a member of the novel or nPKC family. A functional role for PKCtheta is unknown. The present studies demonstrate that PKCtheta is cleaved in the third variable region (V3) in apoptosis induced by diverse agents. PKCtheta cleavage is blocked in cells that overexpress the anti-apoptotic Bcl-xL or the baculovirus p35 protein. PKCtheta is cleaved by Caspase-3 and by apoptotic cell lysates at a DEVD354/K site. We also show that overexpression of the cleaved kinase-active PKCtheta fragment, but not full-length PKCtheta or a kinase-inactive fragment, results in induction of sub-G1 phase DNA, nuclear fragmentation, and lethality. These findings indicate that proteolytic cleavage of PKCtheta by Caspase-3 induces events characteristic of apoptosis.
Recovery with limited replay: fault-tolerant processes in Linda (2002)

Research in the area of fault-tolerant distributed systems has focused to a large extent on data surviving various forms of failure. However, in environments where cooperation among processes is important the authors argue that high availability of processes, in addition to their recoverability is crucial. Their specific interest is in the Linda tuple space paradigm. They discuss efficient techniques for making Linda processes recoverable and outline some characteristics of Linda that make it particularly suitable for implementing fault-tolerance. They also propose a simple extension to their recoverable process mechanism that makes processes highly available.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Stromal expression of 72 kda type IV collagenase (MMP-2) and TIMP-2 mRNAs in colorectal neoplasia. (1992)

We undertook an in situ hybridization study to localize the mRNAs for the 72 kda type IV collagenase (MMP-2) and its specific inhibitor (TIMP-2) in 12 colorectal carcinomas, 3 adenomas, and 4 uninvolved resection margins to see how their distributions correlated with that of the reported distribution of MMP-2 protein. Labeling for MMP-2 and TIMP-2 mRNAs was detectable in 10 of 12 carcinomas and in 2 of 3 adenomas. Unexpectedly, we found much stronger signals for MMP-2 and TIMP-2 mRNAs within the mesenchymal cells in the desmoplastic stroma, of endothelial and/or (myo)fibroblastic nature, rather than in tumor epithelial cells in which localization of MMP-2 was anticipated. Our data indicate that stromal cells may have the ability to synthesize a metalloproteinase that degrades basement membrane, and may together with the neoplastic epithelial cells participate actively in the tissue remodeling and disruption of the basement membrane integrity which is characteristic of invasive tumors.
SLAP lesions in association with complete tears of the long head of the biceps tendon: A report of two cases (1992)

Two patients were found to have superior labrum anterior and posterior (SLAP) lesions in association with complete tears of the long head of the biceps. Additional intraarticular pathology (retained biceps stump, loose body, and glenoid chondromalacia) was discovered in one patient. We recommend arthroscopy of the shoulder in two situations associated with rupture of the long head of the biceps: (a) in patients with acute ruptures in which the decision has been made to do a biceps tenodesis; and (b) in patients with persistent longstanding shoulder symptoms following nonoperative management.
Little Effect of Ordinary Antihypertensive Therapy on Nocturnal High Blood Pressure in Patients with Sleep Disordered Breathing (1998)

The antihypertensive effects of four different antihypertensive medications (beta-blocking agent, atenolol 50 mg; calcium-antagonist, isradipine SRO [slow release] 2.5 mg; diuretic, hydrochlorothiazide [HCTZ] 25 mg; and angiotension converting enzyme-inhibitor, spirapril 6 mg) on obese patients with sleep disordered breathing and hypertension were compared by the ambulatory blood pressure measurement (ABPM). Eighteen patients were randomized in a double-blind, crossover fashion to receive each of the four different medications for 8 weeks. ABPM was performed at baseline and after an 8-week treatment with these medications. A 2- to 3-week washout period occurred both at baseline and between each of the four medications. Three patients were omitted from statistical analysis because of technical problems of ABPM. Atenolol, isradipine SRO, and spirapril decreased significantly (P < .01) the mean 24-h systolic blood pressure, whereas HCTZ did not. The mean 24-h diastolic blood pressure decreased significantly after all four medications: 12 (SD+/-14) mm Hg with atenolol, 7 (SD+/-10) mm Hg with isradipine SRO, 3 mm Hg (SD+/-14) with HCTZ, and 6 (SD+/-15) mm Hg with spirapril (P < .01). During nighttime none of the medications reduced the mean diastolic or systolic blood pressure significantly. According to the 24-h blood pressure curve the influence of these four medications during the whole measurement period was not similar. Atenolol and spirapril lost their antihypertensive effect during the early morning hours. The antihypertensive effect of HCTZ varied markedly from hour to hour. The trough-to-peak ratio of no medication was >0.50. Negative correlation was observed between the apnea time and the mean systolic 24-h (r = -0.604, P = NS) and the mean systolic nocturnal blood pressure change (r = -0.590, P = NS). Our study revealed that the daytime high blood pressure was quite easily controlled by the ordinary monotherapy in these patients with partial upper airway obstruction and hypertension. Instead none of the medications used decreased nocturnal high blood pressure markedly.
Unprecedented ultra-high hydrogen gas sensitivity in undoped titania nanotubes (2005)

A highly ordered array of micron-length undoped titania nanotubes exhibits an unprecedented variation in electrical resistance of about 8.7 orders of magnitude (50 000 000 000%), at room temperature, when exposed to alternating atmospheres of nitrogen containing 1000 ppm hydrogen and air. This represents the largest known change in electrical properties of any material, to any gas, at any temperature. The nanotube arrays were fabricated using anodic oxidation of titanium foil in a pH 4.0 electrolyte containing potassium fluoride, sodium hydrogen sulfate monohydrate and sodium citrate tribasic dihydrate. The dramatic change in resistance is believed to be due to the highly active surface states on the nanoscale walls of the tubes, high surface area of the nanotube architecture, and the well-ordered geometry allowing for hydrogen-sensitive tube-to-tube electrical connections.