gebhart/patrepeval huggingface dataset:
Gene therapy clinical trials worldwide 1989–2004—an overview (2004)

In 1989, Rosenberg et al. performed the first human gene therapy trial when they used a retrovirus to introduce the gene coding for resistance to neomycin into human tumor-infiltrating lymphocytes before infusing them into five patients with advanced melanoma. This study demonstrated the feasibility of using retroviral gene transduction in humans and set the stage for further studies. Since then, over 900 clinical trials have been completed, are ongoing or have been approved worldwide. These trials have been designed to establish feasibility and safety, to demonstrate the reality of expression of therapeutic protein(s) in vivo by the genes transferred and, in some cases, to show therapeutic benefit. There is no single source of information that presents an overview of all the clinical trials undertaken worldwide. In 1997 we set up a database to bring all the information on clinical trials together as comprehensively and as globally as possible. The data were compiled and are regularly updated from official agency sources, the published literature, presentations at conferences and from information kindly provided by investigators or trial sponsors themselves. As of January 31, 2004, we have identified 918 trials in 24 countries. The USA accounts for two-thirds of these trials. Cancer is by far the most common disease indication, followed by inherited monogenic diseases, and cardiovascular diseases. Viral vectors have been the most frequently used vehicles for transferring genes into human cells, with retroviruses and adenoviruses representing the vast majority. Plasmid (naked) DNA and other non-viral vectors have been used in one-quarter of the trials. Over 100 distinct genes have been transferred. This article aims to provide a descriptive overview of the clinical trials that, to the best of our knowledge, have been or are being performed worldwide. Details of the data presented, including an interactive, searchable database that currently holds information on 918 trials, can be found on The Journal of Gene Medicine clinical trials website 1.
Low-Temperature Anomaly in the Josephson Critical Current of Junctions ind-Wave Superconductors (1996)

We show that the Josephson critical current increases rapidly with decreasing temperature near $T\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}0$ for tunnel junctions between anisotropic superconductors. The enhancement of the critical current has its physical origin in the midgap states bound to the tunnel barrier. The magnitude of the zero-temperature peak in a realistic junction is shown to be sensitive to the barrier transparency and barrier roughness. For some crystal orientations we find a transition from a traditional $0$ junction to the unconventional $\ensuremath{\pi}$ junction with decreasing temperature.
Comparison of ( 18 F)Fluoropropylating Agents for 18 F-Radiolabeling of Amines (2000)

It has been demonstrated that [ 18 F]fluoroalkylating agents are useful prosthetic groups for radiofluorination of amines which are contained in many positron emission tomography (PET) radiopharmaceuticals. These agents can be synthesized from disubstituted alkanes, in which the disubstituted propanes are shown to give higher radiochemical yield than the corresponding methanes and ethanes upon radiofluorination. 1-3 Although some [ 18 F]fluoropropylating agents have been investigated, chemical purity of the resulting N-[ 18 F]fluoroalkylamines has not been significantly examined. 1,3 We therefore compared and analyzed the most commonly used [ 18 F]fluoropropylating agents with respect to precursor availability, labeling conditions and the chemical purity of the N-alkylated product, 1-(3-[ 18 F]fluoropropyl)-4-phenylpiperazine ([ 18 F]1). 1-Phenylpiperazine (2) was selected as an amine for [ 18 F]fluoropropylation, since many neuropharmaceuticals contain phenylpiperazine moieties. 4-6
Estimating Amino Acid Substitution Models: A Comparison of Dayhoff's Estimator, the Resolvent Approach and a Maximum Likelihood Method (2002)

Evolution of proteins is generally modeled as a Markov process acting on each site of the sequence. Replacement frequencies need to be estimated based on sequence alignments. Here we compare three approaches: First, the original method by Dayhoff, Schwartz, and Orcutt (1978) Atlas Protein Seq. Struc. 5:345-352, secondly, the resolvent method (RV) by Müller and Vingron (2000) J. Comput. Biol. 7(6):761-776, and finally a maximum likelihood approach (ML) developed in this paper. We evaluate the methods using a highly divergent and inhomogeneous set of sequence alignments as an input to the estimation procedure. ML is the method of choice for small sets of input data. Although the RV method is computationally much less demanding it performs only slightly worse than ML. Therefore, it is perfectly appropriate for large-scale applications.
Multi-step synthesis of nanoparticles performed on millisecond time scale in a microfluidic droplet-based system (2004)

This paper reports a plug-based, microfluidic method for performing multi-step chemical reactions with millisecond time-control. It builds upon a previously reported method where aqueous reagents were injected into a flow of immiscible fluid (fluorocarbons)(H. Song et al., Angew. Chem. Int. Ed., 2003, 42, 768). The aqueous reagents formed plugs--droplets surrounded and transported by the immiscible fluid. Winding channels rapidly mixed the reagents in droplets. This paper shows that further stages of the reaction could be initiated by flowing additional reagent streams directly into the droplets of initial reaction mixture. The conditions necessary for an aqueous stream to merge with aqueous droplets were characterized. The Capillary number could be used to predict the behavior of the two-phase flow at the merging junction. By transporting solid reaction products in droplets, the products were kept from aggregating on the walls of the microchannels. To demonstrate the utility of this microfluidic method it was used to synthesize colloidal CdS and CdS/CdSe core-shell nanoparticles.
Bone marrow transplantation for mucopolysaccharidosis type I: experience of two British centres (1997)

Bone marrow transplantation was carried out on 38 patients with mucopolysaccharidosis type I over a period of 15 years. The donor was an HLA identical relative in 10 cases, an HLA non-identical relative in 16 cases, and an HLA identical unrelated volunteer donor in 12 cases. Ten patients received a second transplant. One patient received three transplants. Thirteen engrafted patients have survived five years or more. Most patients have shown an arrest or slowing down of psychomotor regression. However, dysostosis multiplex has progressed. Careful selection of patients may be necessary to ensure optimum results.
Human Peripheral Blood T Regulatory Cells (Tregs), Functionally Primed CCR4+ Tregs and Unprimed CCR4− Tregs, Regulate Effector T Cells Using FasL (2007)

Regulatory CD25(+)CD4(+) T cells (Tregs) play an important role in the control of peripheral tolerance. In this study we demonstrate that human peripheral blood Tregs can be divided into two distinct populations based on the expression of CCR4. The majority ( approximately 75%) of freshly isolated Tregs express CCR4 and presumably represent memory-type Tregs. Interestingly, CCR4(-) Tregs require anti-CD3 Ab-mediated activation to acquire a regulatory activity, while CCR4(+) Tregs appear to be already primed to suppress the proliferation of CD8(+) T cells. CCR4 is also expressed on CD25(low)CD4(+) T cells (CCR4(+) non-Tregs) that mostly suppress Th1-type polarization without affecting T cell proliferation, presumably via the production of immunomodulatory cytokines like IL-10. In contrast, CCR4(+) Tregs express FasL to primarily regulate T cell proliferation via a contact-mediated process involving FasL/Fas signaling, a major regulatory pathway of T cell homeostasis. Finally, we also demonstrate that the depletion of CCR4(+) T cells leads to Th1-type polarization of CD4(+) T cells and augmentation of CD8(+) T cell responses to tumor Ags.
Abundance and Frequency of the Asiatic Oak Weevil (Coleoptera: Curculionidae) and Defoliation on American, Chinese, and Hybrid Chestnut (Castanea) (2016)

The Asiatic oak weevil, Cyrtepistomus castaneus Roelofs (Coleoptera: Curculionidae), is a nonnative defoliator of trees in the Fagaceae family in the United States but has not been studied on Castanea species in the southern Appalachian Mountains. Planted trees of Castanea dentata (Marsh.) Borkh. (Fagales: Fagaceae), Castanea mollissima Blume (Fagales: Fagaceae), and four hybrid breeding generations were evaluated in 2012 for insect defoliation and C. castaneus abundance and frequency. Defoliation was visually assessed throughout the growing season at two sites in the southern Appalachian Mountains (western North Carolina and eastern Tennessee). C. castaneus abundance and frequency were monitored on trees using beat sheets and emergence was recorded from ground traps. Asiatic oak weevils were more abundant and more frequently collected on American chestnut (Ca. dentata) and its most closely related BC3F3 hybrid generation than on the Asian species Ca. mollissima. In most months, C. castaneus colonization of hybrid generations was not significantly different than colonization of parental species. Frequency data for C. castaneus suggested that adults were distributed relatively evenly throughout the study sites rather than in dense clusters. Emergence of C. castaneus was significantly higher under a canopy dominated by Quercus species than under non-Quercus species or open sky. C. castaneus emergence began in May and peaked in late June and early July. These results may be useful for resource managers trying to restore blight-resistant chestnut to the Southern Appalachians while minimizing herbivory by insect pests.
Endothelin A Receptor Antagonism and Angiotensin-Converting Enzyme Inhibition Are Synergistic via an Endothelin B Receptor–Mediated and Nitric Oxide–Dependent Mechanism (2004)

Animal studies suggest that endothelin A (ETA) receptor antagonism and angiotensin-converting enzyme (ACE) inhibition may be synergistic. This interaction and the role of ETB receptors and endothelial mediators were investigated in terms of systemic and renal effects in humans in two studies. In one study, six subjects received placebo, the ETA receptor antagonist BQ-123 alone, and BQ-123 in combination with the ETB receptor antagonist BQ-788 after pretreatment with the ACE inhibitor enalapril (E) or placebo. In the other, six subjects who were pretreated with E received placebo, BQ-123, and BQ-123 with concomitant inhibition of nitric oxide (NO) synthase or cyclo-oxygenase (COX). Both were randomized, double-blind, crossover studies. Mean arterial pressure was reduced by BQ-123, an effect that was doubled during ACE inhibition (mean area under curve +/- SEM; BQ-123, -2.3 +/- 1.8%; BQ-123+E, -5.1 +/- 1.1%; P < 0.05 versus placebo). BQ-123 increased effective renal blood flow (BQ-123, -0.1 +/- 2.4%; BQ-123+E, 10.9 +/- 4.2%; P < 0.01 versus BQ-123), reduced effective renal vascular resistance (BQ-123, -1.2 +/- 3.1%; BQ-123+E, -12.8 +/- 3.0%; P < 0.01 versus placebo and versus BQ-123), and increased urinary sodium excretion markedly (BQ-123, 2.6 +/- 12.8%; BQ-123+E, 25.2 +/- 12.6%; P < 0.05 versus BQ-123, P < 0.01 versus placebo and versus E) only during ACE inhibition. These effects were abolished by both ETB receptor blockade and NO synthase inhibition, whereas COX inhibition had no effect. In conclusion, the combination of ETA receptor antagonism and ACE inhibition is synergistic via an ETB receptor-mediated, NO-dependent, COX-independent mechanism. The reduction of BP and renal vascular resistance and associated substantial natriuresis make this a potentially attractive therapeutic combination in renal disease.
GLP-1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans (1999)

The aim of the present study was to assess the effect of glucagon-like peptide-1 (GLP-1) on solid gastric emptying and the subsequent release of pancreatic and intestinal hormones. In eight men [age 33.6 +/- 2.5 yr, body mass index 24.1 +/- 0.9 (means +/- SE)], scintigraphic solid gastric emptying during infusion of GLP-1 (0.75 pmol. kg(-1). min(-1)) or saline was studied for 180 min. Concomitantly, plasma concentrations of C- and N-terminal GLP-1, glucose, insulin, C-peptide, glucagon, and peptide YY (PYY) were assessed. Infusion of GLP-1 resulted in a profound inhibition of both the lag phase (GLP-1: 91.5, range 73.3-103.6 min vs. saline: 19. 5, range 10.2-43.4 min) and emptying rate (GLP-1: 0.34, range 0.06-0. 56 %/min vs. saline: 0.84, range 0.54-1.33 %/min; P < 0.01 for both) of solid gastric emptying. Concentrations of both intact and total GLP-1 were elevated to supraphysiological levels. Plasma glucose and glucagon concentrations were below baseline during infusion of GLP-1 in contrast to saline infusion, where concentrations were elevated above baseline (both P < 0.001). The insulin and C-peptide responses were lower during infusion with GLP-1 than with saline (P < 0.004 and P < 0.001, respectively). Plasma PYY concentrations decreased below baseline during GLP-1 infusion in contrast to saline, where concentrations were elevated above baseline (P = 0.04). Infusion of GLP-1 inhibits solid gastric emptying with secondary effects on the release of insulin, C-peptide, and glucagon, resulting in lower plasma glucose concentrations. In addition, the release of PYY into the circulation is inhibited by GLP-1 infusion, suggesting a negative feedback of GLP-1 on the function of the L-cell.
La ilustración en colombia (1991)

(Presentación y compilación). Bogotá: Universidad Santo Tomás, Biblioteca Colombiana de Filosofía 15 (1990). 382 pp.
ChemInform Abstract: 3‐Carboxamido Analogues of Morphine and Naltrexone: Synthesis and Opioid Receptor Binding Properties. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Performance of bulk heterojunction photovoltaic devices prepared by airbrush spray deposition (2008)

We have used airbrush spray deposition to fabricate organic photovoltaic devices with an active layer composed of a blend of poly(3-hexylthiophene) and [6,6]-phenyl-C61 butyric acid methyl ester. Working devices were prepared in ambient conditions from a variety of common organic solvents; active layers prepared from chlorobenzene exhibit improved homogeneity, resulting in narrower distributions of the relevant device parameters. Further studies on devices prepared from chlorobenzene showed that annealing at 120°C for 10min resulted in optimum performance, and that an active layer thickness of 150nm resulted in a maximum efficiency of 2.35% under AM1.5 illumination at 1sun.
Identification of AUF1 (Heterogeneous Nuclear Ribonucleoprotein D) as a Component of the α-Globin mRNA Stability Complex (1997)

mRNA turnover is an important regulatory component of gene expression and is significantly influenced by ribonucleoprotein (RNP) complexes which form on the mRNA. Studies of human alpha-globin mRNA stability have identified a specific RNP complex (alpha-complex) which forms on the 3' untranslated region (3'UTR) of the mRNA and appears to regulate the erythrocyte-specific accumulation of alpha-globin mRNA. One of the protein activities in this multiprotein complex is a poly(C)-binding activity which consists of two proteins, alphaCP1 and alphaCP2. Neither of these proteins, individually or as a pair, can bind the alpha-globin 3'UTR unless they are complexed with the remaining non-poly(C) binding proteins of the alpha-complex. With the yeast two-hybrid screen, a second alpha-complex protein was identified. This protein is a member of the previously identified A+U-rich (ARE) binding/degradation factor (AUF1) family of proteins, which are also known as the heterogeneous nuclear RNP (hnRNP) D proteins. We refer to these proteins as AUF1/hnRNP-D. Thus, a protein implicated in ARE-mediated mRNA decay is also an integral component of the mRNA stabilizing alpha-complex. The interaction of AUF1/hnRNP-D is more efficient with alphaCP1 relative to alphaCP2 both in vitro and in vivo, suggesting that the alpha-complex might be dynamic rather than a fixed complex. AUF1/hnRNP-D could, therefore, be a general mRNA turnover factor involved in both stabilization and decay of mRNA.
Alkali and Hybrid-Alkali Flooding as a Tertiary Oil Recovery Mode: Prospects and Challenges (2016)

to play a bigger role in the future to meet the energy demand and economics. This paper presents a comprehensive review of EOR technologies related to alkaline flooding and its hybrids. Alkaline flooding is one of the chemical enhanced oil recovery techniques in which high pH alkaline chemicals are injected to the reservoir for recovering the residual oil. It is among the oldest EOR techniques and its history started way back in the early 20 th century. The history of alkaline flooding, mechanisms by which it recovers oil, different process variations, the effectiveness and costs of different alkalis, problems associated with alkaline flooding and its application in carbonates are briefly reviewed in this paper. This paper also focuses on the reviews of the application of various hybrid floods developed along with alkali and their advantages, limitations both in clastic and carbonate reservoirs. The technical solutions to some of these challenges will be discussed.
Comparison of the enzymatic activities of native and recombinant protein phosphatase-1 toward histone. (1994)

The activities of native and recombinant rabbit muscle protein phosphatase-1 toward phosphorylated lysine-rich histone and phosphorylase a were compared. The activity of rabbit muscle protein phosphatase-1 toward histone is strongly stimulated by Mn++. In the case of the recombinant enzyme, both phosphorylase phosphatase and histone phosphatase activities exhibit a dependence on Mn++. Examination of the activities of both enzymes assayed under optimal conditions show that they exhibit similar substrate specificities toward histone and phosphorylase, contrary to previous claims (Alessi et al., Eur. J. Biochem. 213, 1055-1066, 1993).
Ozone’s Impact on Public Health: Contributions from Indoor Exposures to Ozone and Products of Ozone-Initiated Chemistry (2006)

Indoor exposures to ozone and its oxidation products can be reduced by filtering ozone from ventilation air and limiting the indoor use of products and materials whose emissions react with ozone. Such steps might be especially valuable in schools, hospitals, and childcare centers in regions that routinely experience elevated outdoor ozone concentrations.
Celecoxib Promotes c-FLIP Degradation through Akt-Independent Inhibition of GSK3 (2011)

Celecoxib is a COX-2 inhibitor that reduces the risk of colon cancer. However, the basis for its cancer chemopreventive activity is not fully understood. In this study, we defined a mechanism of celecoxib action based on degradation of cellular FLICE-inhibitory protein (c-FLIP), a major regulator of the death receptor pathway of apoptosis. c-FLIP protein levels are regulated by ubiquitination and proteasome-mediated degradation. We found that celecoxib controlled c-FLIP ubiquitination through Akt-independent inhibition of glycogen synthase kinase-3 (GSK3), itself a candidate therapeutic target of interest in colon cancer. Celecoxib increased the levels of phosphorylated GSK3, including the α and β forms, even in cell lines, where phosphorylated Akt levels were not increased. Phosphoinositide 3-kinase inhibitors abrogated Akt phosphorylation as expected but had no effect on celecoxib-induced GSK3 phosphorylation. In contrast, protein kinase C (PKC) inhibitors abolished celecoxib-induced GSK3 phosphorylation, implying that celecoxib influenced GSK3 phosphorylation through a mechanism that relied upon PKC and not Akt. GSK3 blockade either by siRNA or kinase inhibitors was sufficient to attenuate c-FLIP levels. Combining celecoxib with GSK3 inhibition enhanced attenuation of c-FLIP and increased apoptosis. Proteasome inhibitor MG132 reversed the effects of GSK3 inhibition and increased c-FLIP ubiquitination, confirming that c-FLIP attenuation was mediated by proteasomal turnover as expected. Our findings reveal a novel mechanism through which the regulatory effects of c-FLIP on death receptor signaling are controlled by GSK3, which celecoxib acts at an upstream level to control independently of Akt.
Kraken: ultrafast metagenomic sequence classification using exact alignments (2014)

Kraken is an ultrafast and highly accurate program for assigning taxonomic labels to metagenomic DNA sequences. Previous programs designed for this task have been relatively slow and computationally expensive, forcing researchers to use faster abundance estimation programs, which only classify small subsets of metagenomic data. Using exact alignment of k-mers, Kraken achieves classification accuracy comparable to the fastest BLAST program. In its fastest mode, Kraken classifies 100 base pair reads at a rate of over 4.1 million reads per minute, 909 times faster than Megablast and 11 times faster than the abundance estimation program MetaPhlAn. Kraken is available at http://ccb.jhu.edu/software/kraken/.
Further Naphthylcombretastatins. An Investigation on the Role of the Naphthalene Moiety (2004)

By synthesis and biological studies of new naphthalene analogues of combretastatins, we have found that the naphthalene is a good surrogate for the isovanillin moiety (3-hydroxy-4-methoxyphenyl) of combretastatin A-4, always generating highly cytotoxic analogues when combined with the 3,4,5-trimethoxyphenyl or related systems. On the other hand, when the naphthalene replaces the 3,4,5-trimethoxyphenyl moiety, the cytotoxic activity is largely decreased. The most cytotoxic naphthalene analogues of combretastatins, which also produce inhibition of tubulin polymerization, exerted their antimitotic effects through microtubule network disruption and subsequent G(2)/M arrest of the cell cycle in human cancer cells.
Neural Networks for Control (1993)

This paper starts by placing neural net techniques in a general nonlinear control framework. After that, several basic theoretical results on networks are surveyed.
Oxygen Extraction Ratio: A Valid Indicator of Transfusion Need in Limited Coronary Vascular Reserve? (1992)

We have described whole body oxygen (O2) extraction ratio (ER) as a reliable indicator of transfusion need in acute normovolemic anemia. In normal hearts, myocardial lactate production (–LACT), indicating anaerobic metabolism, does not occur until the ER >50% and Hct <10%. It is not known if the ER is valid in the setting of limited coronary vascular reserve. This study assesses the effect of a critical left anterior descending (LAD) coronary stenosis on the compensation to acute blood loss anemia. Adult dogs were anesthetized, paralyzed, and mechanically ventilated. A critical LAD stenosis was created in seven animals (STEN). There were seven controls (CON). Animals underwent isovolemic exchange transfusion with 6% HES until cardiac failure (CF). Catheters were placed in the aorta, pulmonary artery, and anterior interventricular coronary vein. Cardiac failure occurred at Hct = 8.6% ± 0.4% in the CON and 17.0% ± 0.5% in the STEN animals. Cardiac output increased in the CON, but not in the STEN animals. Blood flow in the LAD increased in the CON but not the STEN animals. –LACT began in the CON and STEN animals at Hct <20% and coincided with an ER >50% in both groups. We conclude that CF occurs at a higher hematocrit with a critical LAD stenosis. The whole body ER >50% remains a valid indicator of myocardial metabolism in anemia in the presence of limited coronary vascular reserve. The ER may be a useful guide to transfusion therapy.