gebhart/patrepeval huggingface dataset:
A Retroviral Vector That Allows Efficient Co-Expression of Two Genes and the Versatility of Alternate Selection Markers (1997)

pZIG(hGCSFR) is a retroviral vector that can co-express two genes and also provides alternative selection markers. This retroviral vector has been constructed to incorporate an internal ribosome entry site (IRES) element to co-express two exogenous genes in mammalian cells. Two marker/selection genes have been cloned into the vector that not only allow the efficiency of co-expression to be quantified but also provide versatility of selection criteria. A cDNA encoding the hGCSFR (signaling deficient) was cloned as the 5' cistron, and a gene encoding a neomycin-resistance and beta-galactosidase (beta geo) fusion protein was cloned as the 3' cistron. The two marker genes cloned in this retroviral vector allow the selection and isolation of mammalian cells following either transient (by fluorescence-activating cell sorting analysis of hGCSFR-positive cells) or stable (neomycin resistance) infection with the certainty that over 93% of clones will co-express both genes. This novel vector offers a versatile retroviral vector that can be potentially used in a wide range of gene therapy applications as the gene of interest can be coexpressed with either of the marker genes depending on whether the retroviral infection is to be performed in vitro, in vivo, or ex vivo.
Double-Blind Study of the Safety of Clopidogrel With and Without a Loading Dose in Combination With Aspirin Compared With Ticlopidine in Combination With Aspirin After Coronary Stenting (2000)

The safety/tolerability of clopidogrel (plus aspirin) is superior to that of ticlopidine (plus aspirin) (P=0.005). The 300-mg loading dose was well tolerated, notably with no increased risk of bleeding. Secondary end point data are consistent with the hypothesis that clopidogrel and ticlopidine have comparable efficacy with regard to cardiac events after successful stenting.
Substrate-Based Design of the First Class of Angiotensin-Converting Enzyme-Related Carboxypeptidase (ACE2) Inhibitors (2002)

Angiotensin-converting enzyme-related carboxypeptidase (ACE2) is a recently identified zinc metalloprotease with carboxypeptidase activity that was identified using our genomics platform. We implemented a rational design approach to identify potent and selective ACE2 inhibitors. To this end, picomolar inhibitors of ACE2 were designed and synthesized.
Correlation of Expression of Cyclooxygenase-2, Vascular Endothelial Growth Factor, and Peroxisome Proliferator–Activated Receptor δ With Head and Neck Squamous Cell Carcinoma (2001)

Cyclooxygenase (COX) is the rate-limiting enzyme in the formation of prostaglandins from arachidonic acid. COX exists in 2 isoforms, COX-1 and COX-2. These isoforms are encoded by separate genes and demonstrate cell-specific expression and regulation. Peroxisome proliferator-activated receptor delta (PPARdelta) is a nuclear transcription factor that is activated by prostacyclin. Vascular endothelial growth factor (VEGF) is a proangiogenic factor that is up-regulated in various tumors. Vascular endothelial growth factor has been shown to interact with COX-derived prostaglandins in angiogenesis. To better understand the roles of these genes in head and neck squamous cell carcinoma (HNSCCA), we examined the differential expression of the COX1, COX2, VEGF, and PPARdelta genes in these tumors. Tissue samples from patients with HNSCCA were analyzed for COX-1, COX-2, VEGF, and PPARdelta messenger RNAs (mRNAs) by in situ hybridization. COX-1 and COX-2 mRNAs were also evaluated with Northern blot hybridization. Immunohistochemistry was used to analyze for COX-2 and PPARdelta proteins. Results showed focal areas of accumulation for COX-2, VEGF, and PPARdelta but not COX-1 in human HNSCCA. Northern blot hybridization showed higher levels of COX-2 mRNA in HNSCCA than in normal tissue. This suggests a supportive role of COX-2 in development and/or progression of HNSCCA. In addition, PPARdelta may be a receptor for COX-2-produced prostaglandins in HNSCCA. There is a potential role for selective COX-2 inhibitors in the treatment of these lesions.
Localization of Nitration and Chlorination Sites on Apolipoprotein A-I Catalyzed by Myeloperoxidase in Human Atheroma and Associated Oxidative Impairment in ABCA1-dependent Cholesterol Efflux from Macrophages (2004)

We recently reported that apolipoprotein A-I (apoA-I), the major protein component of high density lipoprotein, is a selective target for myeloperoxidase (MPO)-catalyzed nitration and chlorination in both and serum of subjects with cardiovascular disease. We further showed that the extent of both apoA-I nitration and chlorination correlated with functional impairment in reverse cholesterol transport activity of the isolated lipoprotein. Herein we used tandem mass spectrometry to map the sites of MPO-mediated apoA-I nitration and chlorination in vitro and in vivo and to relate the degree of site-specific modifications to loss of apoA-I lipid binding and cholesterol efflux functions. Of the seven tyrosine residues in apoA-I, Tyr-192, Tyr-166, Tyr-236, and Tyr-29 were nitrated and chlorinated in MPO-mediated reactions. Site-specific liquid chromatography-mass spectrometry quantitative analyses demonstrated that the favored modification site following exposure to MPO-generated oxidants is Tyr-192. MPO-dependent nitration and chlorination both proceed with Tyr-166 as a secondary site and with Tyr-236 and Tyr-29 modified only minimally. Parallel functional studies demonstrated dose-dependent losses of ABCA1-dependent cholesterol acceptor and lipid binding activities with apoA-I modification by MPO. Finally tandem mass spectrometry analyses showed that apoA-I in human atherosclerotic tissue is nitrated at the MPO-preferred sites, Tyr-192 and Tyr-166. The present studies suggest that site-specific modifications of apoA-I by MPO are associated with impaired lipid binding and ABCA1-dependent cholesterol acceptor functions, providing a molecular mechanism that likely contributes to the clinical link between MPO levels and cardiovascular disease risk.
Translational medicine: the antihypertensive effect of renal denervation (2009)

Translational medicine is concerned with the translation of research discoveries into clinical applications for the prevention, diagnosis, and treatment of human diseases. Here we briefly review the research concerning the role of the renal sympathetic nerves (efferent and afferent) in the control of renal function, with particular reference to hypertension. The accumulated evidence is compelling for a primary role of the renal innervation in the pathogenesis of hypertension. These research discoveries led to the development of a catheter-based procedure for renal denervation in human subjects. A proof-of-principle study in patients with hypertension resistant to conventional therapy has demonstrated that the procedure is safe and produces renal denervation with sustained lowering of arterial pressure.
Characterization and immunolocalization of a Cryptosporidium protein containing repeated amino acid motifs (1993)

The oocyst wall is one of the components that permits cryptosporidia both to survive in the environment and to retain infectivity. With the aim of identifying Cryptosporidium proteins specifically expressed at the oocyst stage, we screened lambda gt11 genomic libraries of Cryptosporidium parvum with both an oocyst antiserum and a specific genetic probe. We isolated, from distinct libraries, two overlapping clones containing an open reading frame encoding a 1,252-amino-acid polypeptide. The analysis of the deduced amino acid sequence revealed unusually high contents of cysteine, proline, and histidine. The sequence was also characterized by two distinct amino acid motifs, each repeated several times. The DNA sequences coding for the amino acid repeats showed a high frequency of synonymous mutations, a result suggesting that the repeated motifs may be functionally and/or structurally important to the parasite. Antisera and monoclonal antibodies developed against a recombinant polypeptide encompassing the first 786 amino acids revealed that the corresponding protein in C. parvum had an apparent molecular weight of 190,000. Moreover, confocal microscopy analysis with immunofluorescence indicated that the protein was localized on the oocyst wall as a uniform stain and within the oocyst itself as bright granules in close association with the residual body.
Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA (2007)

The results of administering escalating, i.v. doses of targeted nanoparticles containing a siRNA targeting the M2 subunit of ribonucleotide reductase to non-human primates are reported. The nanoparticles consist of a synthetic delivery system that uses a linear, cyclodextrin-containing polycation, transferrin (Tf) protein targeting ligand, and siRNA. When administered to cynomolgus monkeys at doses of 3 and 9 mg siRNA/kg, the nanoparticles are well tolerated. At 27 mg siRNA/kg, elevated levels of blood urea nitrogen and creatinine are observed that are indicative of kidney toxicity. Mild elevations in alanine amino transferase and aspartate transaminase at this dose level indicate that the liver is also affected to some extent. Analysis of complement factors does not reveal any changes that are clearly attributable to dosing with the nanoparticle formulation. Detection of increased IL-6 levels in all animals at 27 mg siRNA/kg and increased IFN-gamma in one animal indicate that this high dose level produces a mild immune response. Overall, no clinical signs of toxicity clearly attributable to treatment are observed. The multiple administrations spanning a period of 17-18 days enable assessment of antibody formation against the human Tf component of the formulation. Low titers of anti-Tf antibodies are detected, but this response is not associated with any manifestations of a hypersensitivity reaction upon readministration of the targeted nanoparticle. Taken together, the data presented show that multiple, systemic doses of targeted nanoparticles containing nonchemically modified siRNA can safely be administered to non-human primates.
Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide (2015)

Liraglutide is an acylated glucagon-like peptide-1 (GLP-1) analogue that binds to serum albumin in vivo and is approved for once-daily treatment of diabetes as well as obesity. The aim of the present studies was to design a once weekly GLP-1 analogue by increasing albumin affinity and secure full stability against metabolic degradation. The fatty acid moiety and the linking chemistry to GLP-1 were the key features to secure high albumin affinity and GLP-1 receptor (GLP-1R) potency and in obtaining a prolonged exposure and action of the GLP-1 analogue. Semaglutide was selected as the optimal once weekly candidate. Semaglutide has two amino acid substitutions compared to human GLP-1 (Aib(8), Arg(34)) and is derivatized at lysine 26. The GLP-1R affinity of semaglutide (0.38 ± 0.06 nM) was three-fold decreased compared to liraglutide, whereas the albumin affinity was increased. The plasma half-life was 46.1 h in mini-pigs following i.v. administration, and semaglutide has an MRT of 63.6 h after s.c. dosing to mini-pigs. Semaglutide is currently in phase 3 clinical testing.
Early Endothelial Dysfunction Predicts the Development of Transplant Coronary Artery Disease at 1 Year Posttransplant (1996)

Paired studies that used intravascular ultrasound showed that early endothelial dysfunction predicts the development of allograft arteriosclerosis during the initial year posttransplant. This early pathophysiological feature is likely an important marker that could be useful in therapeutic trials.
Electrical characteristics and contact resistance of B+-and BF2 +-implanted silicon diodes with furnace and rapid thermal annealing (1985)

Shallow p <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> -n junctions in silicon are fabricated by the implantation of 10 keV B <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> or 50 keV BF <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</inf> ions at a fluence of 3 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">15</sup> / cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> through a capping layer of 25-nm SiO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> . Sheet resistance, contact resistivity, and forward and reverse bias leakage current are measured for various furnace and rapid thermal annealing (RTA) conditions. SIMS profiles are included. RTA allows the simultaneous achievement of junctions with j < 4 nA/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">R_{s}\simeq 50 \Omega/</tex> , and <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\rho_{c}\simeq 2 \times 10^{-6}\Omega</tex> . cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> for junction depths of the order of 0.25 µm as mesured by the traditional bevel-and-strain method.
Congo red as a fluorochrome for the rapid detection of fungi (1988)

Congo red may be applied as a fluorochrome to rapidly detect fungi in clinical specimens, tissue, and fungal culture preparations. This generally available stain is cost effective and simple to prepare. The stain may be prepared with potassium permanganate as a counterstain or with Formalin or glutaraldehyde as a fungicide.
miR-365, a Novel Negative Regulator of Interleukin-6 Gene Expression, Is Cooperatively Regulated by Sp1 and NF-κB (2011)

Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a central role in host defense. IL-6 expression can be regulated at both a transcriptional and a post-transcriptional level. We used a combination of bioinformatics and experimental techniques to demonstrate that the miR-365 is a direct negative regulator of IL-6. Overexpression of miR-365 mimics decreased activity of a luciferase reporter containing the IL-6 3'-UTR and led to repression of IL-6 protein. In contrast, ectopic expression of a miR-365 inhibitor elevated IL-6 expression. The negative regulation of miR-365 was strictly dependent on a microRNA binding element in the 3'-UTR of IL-6 mRNA. Deletion mutant analysis of the miR-365 promoter showed that two transcription factors, Sp1 and NF-κB, are essential for the transcriptional regulation of miR-365. We also demonstrate that the MAPK/ERK pathway contributes to the regulation of miR-365. Furthermore, miR-365 exhibited a greater negative regulatory effect on IL-6 than hsa-let-7a, a previously identified microRNA negatively regulating IL-6. Taken together, our results show that miR-365 is a novel negative regulator of IL-6.
Statistical Learning Theory (1999)

A comprehensive look at learning and generalization theory. The statistical theory of learning and generalization concerns the problem of choosing desired functions on the basis of empirical data. Highly applicable to a variety of computer science and robotics fields, this book offers lucid coverage of the theory as a whole. Presenting a method for determining the necessary and sufficient conditions for consistency of learning process, the author covers function estimates from small data pools, applying these estimations to real-life problems, and much more.
Structured light 3D tracking system for measuring motions in PET brain imaging (2010)

Patient motion during scanning deteriorates image quality, especially for high resolution PET scanners. A new proposal for a 3D head tracking system for motion correction in high resolution PET brain imaging is set up and demonstrated. A prototype tracking system based on structured light with a DLP projector and a CCD camera is set up on a model of the High Resolution Research Tomograph (HRRT). Methods to reconstruct 3D point clouds of simple surfaces based on phase-shifting interferometry (PSI) are demonstrated. The projector and camera are calibrated using a simple stereo vision procedure where the projector is treated as a camera. Additionally, the surface reconstructions are corrected for the non-linear projector output prior to image capture. The results are convincing and a first step toward a fully automated tracking system for measuring head motions in PET imaging.
Observation, Replication, and Measurement in Sports Economics (2009)

This paper provides an introduction to the special edition as well as my contribution on the topics covered in this special edition—observation, replication, and measurement issues relevant to sports economists. The papers cover issues related to the professional conveyance of first-hand experience, interaction with related sports analysis communities not governed by peer review or our usual citation requirements, data integrity, data and result replication, and second-hand measurement relevant to particular economic questions. My contribution is in brief descriptions concerning how these issues have intruded on some of my own work.
Dose-ranging efficacy of new once-daily extended-release minocycline for acne vulgaris. (2006)

A multicenter, 12-week, randomized, double-blinded, placebo-controlled, dose-ranging study was conducted in 233 subjects with moderate to severe facial acne vulgaris to determine the lowest effective once-daily oral dose of a new extended-release (ER) minocycline hydrochloride formulation with the safest adverse effect profile. Subjects randomly were assigned to treatment with daily dosages of ER-minocycline 1-, 2-, or 3-mg/kg tablets, or daily placebo tablets, for 84 days. At the end of the 12 weeks, the number of inflammatory lesions decreased approximately 50% from baseline levels in the dose groups. No dose-dependent effect was observed, with the percentage decrease in the number of inflammatory lesions in the 1-mg/kg treatment group being equal to or greater than higher doses. The pairwise difference between the ER-minocycline 1 mg/kg and placebo groups in the percentage decrease in inflammatory lesions was statistically significant (P = .015). Acute vestibular adverse events (AVAEs) appeared to be dose proportional, with the incidence being similar in the lowest (1 mg/kg) dosing group (24%) and in the placebo group (26%). Higher-dose regimens were associated with a higher incidence of central nervous system side effects and AVAEs. A 1-mg/kg daily dosage of the new ER-minocycline formulation is the lowest effective dose with the safest side effect profile, with higher-dose regimens offering no substantial therapeutic advantages.
A liveness detection method for face recognition based on optical flow field (2009)

It is a common spoof to use a photograph to fool face recognition algorithm. In light of differences in optical flow fields generated by movements of two-dimensional planes and three-dimensional objects, we proposed a new liveness detection method for face recognition. Under the assumption that the test region is a two-dimensional plane, we can obtain a reference field from the actual optical flow field data. Then the degree of differences between the two fields can be used to distinguish between a three-dimensional face and a two-dimensional photograph. Empirical study shows that the proposed approach is both feasible and effective.
Production of granulocyte-macrophage colony-stimulating factor by primary cultures of unstimulated rat microvascular endothelial cells (1988)

Small vessel (microvascular) endothelial cells are in close contact with hematopoietic progenitor cells in the bone marrow and therefore may have an important role in hematopoiesis. Although other studies have shown that endothelial cells produce various colony-stimulating factors (CSFs), these studies examined large vessel endothelial cells, which are different in many respects from microvascular endothelial cells and which do not contact cells in the bone marrow. We show in this study that primary cultures of unstimulated rat fat capillary endothelial cells grown in serum-free medium produce a substantial amount of granulocyte-macrophage CSF (GM-CSF). The medium conditioned by these cells stimulated proliferation of two different lines of GM- CSF-responsive cells--PT-18 mast cells and FDC-P1 cells--and supported the growth of cells of the granulocyte and macrophage lines in cultures of rat bone marrow cells. The factor responsible for this activity had physical properties consistent with those of GM-CSF, namely, a similar apparent mol wt by gel filtration, resistance to repeated freeze-thaws, resistance to boiling for ten minutes but not for 30 minutes, and resistance to heating to 56 degrees C for one hour. The factor causing target cell stimulation was not B cell-stimulating factor-1 (BSF-1, or IL 4), since it failed to stimulate a BSF-1-responsive cell line HT2- JH, and target cells (PT-18) did not respond appreciably to recombinant BSF-1. Northern blot analysis of mRNA from rat fat capillary endothelial cells showed high levels of expression of GM-CSF, confirming that this factor is produced by microvascular endothelial cells. This is the first report of CSF production by unstimulated microvascular endothelial cells, demonstrating that these ubiquitous cells are capable of producing sizable amounts of at least one growth factor for hematopoietic progenitor cells.
IL‐3‐Dependent Early Erythropoiesis Is Stimulated by Autocrine Transforming Growth Factor Beta (2004)

Autocrine/paracrine transforming growth factor beta (TGF-beta) is an important regulator of stem cell quiescence and generally suppresses stem cell proliferation. However, we show here that during the first few days of an erythroid cell culture from adult blood stem cells, the presence of neutralizing antibodies against TGF-beta had a suppressive effect on subsequent erythropoiesis, indicating a stimulatory action of autocrine TGF-beta. The suppression occured in the form of a delay in erythroblast proliferation rather than a reduction in final erythroid colony numbers. The inhibitory effect of anti-TGF-beta occured in the presence of interleukin-3 (IL-3) but not in cultures with only stem cell factor and erythropoietin. Erythroblasts expressing gamma-globin (gamma+) were more strongly suppressed than erythroblasts expressing only beta-globin (gamma-beta+), so that stem cell treatment with anti-TGF-beta caused a decrease in the proportion of gamma+ cells. Anti-TGF-beta had an inhibitory effect on erythropoiesis only when administered during the first 4 days of culture, that is, before the onset of globin expression and dependence on erythropoietin. The decreasing effect of anti-TGF-beta with delayed addition coincided with a decreasing dependence on IL-3. CD133+ stem cells were more strongly suppressed by anti-TGF-beta than the complementary CD133-CD34+ stem cells, and the latter were also much less dependent on IL-3. The treatment of very early stem cell cultures with a pulse of added TGF-beta1 in the presence of IL-3 increased the subsequent proliferation of erythroblasts. Taken together, the data suggest that IL-3-driven early erythropoiesis from immature peripheral blood stem cells is stimulated by autocrine TGF-beta.