gebhart/patrepeval huggingface dataset:
Persistent infection of rhesus macaques with T-cell-line-tropic and macrophage-tropic clones of simian/human immunodeficiency viruses (SHIV). (1995)

To elucidate the functions of human immunodeficiency virus type 1 (HIV-1) genes in a nonhuman primate model, we have constructed infectious recombinant viruses (chimeras) between the pathogenic molecular clone of simian immunodeficiency virus (SIV) SIVmac239 and molecular clones of HIV-1 that differ in phenotypic properties controlled by the env gene. HIV-1SF33 is a T-cell-line-tropic virus which induces syncytia, and HIV-1SF162 is a macrophage-tropic virus that does not induce syncytia. A DNA fragment encoding tat, rev, and env (gp160) of SIVmac239 has been replaced with the counterpart genetic region of HIV-1SF33 and HIV-1SF162 to derive chimeric recombinant simian/human immunodeficiency virus (SHIV) strains SHIVSF33 and SHIVSF162, respectively. In the acute infection stage, macaques inoculated with SHIVSF33 had levels of viremia similar to macaques infected with SIVmac239, whereas virus loads were 1/10th to 1/100th those in macaques infected with SHIVSF162. Of note is the relatively small amount of virus detected in lymph nodes of SHIVSF162-infected macaques. In the chronic infection stage, macaques infected with SHIVSF33 also showed higher virus loads than macaques infected with SHIVSF162. Virus persists for over 1 year, as demonstrated by PCR for amplification of viral DNA in all animals and by virus isolation in some animals. Antiviral antibodies, including antibodies to the HIV-1 env glycoprotein (gp160), were detected; titers of antiviral antibodies were higher in macaques infected with SHIVSF33 than in macaques infected with SHIVSF162. Although virus has persisted for over 1 year after inoculation, these animals have remained healthy with no signs of immunodeficiency. These findings demonstrate the utility of the SHIV/macaque model for analyzing HIV-1 env gene functions and for evaluating vaccines based on HIV-1 env antigens.
Implantable Telemetry Systems for Use in Animal Monitoring (1973)

Advances in microelectronics and integrated circuit techniques have now allowed for the creation of small implantable telemetry units which are capable of monitoring a variety of physiological signals. Original efforts were directed toward the use of single-channel units; more recently multichannel units have been utilized. Battery power for multichannel operation has been conserved by the use of implantable radio frequency activated switches. Distance and duration of transmission with such units depends on the available power or use of backpack units which can receive and retransmit the weaker signals. Units have provided information for as long as 2 years in various animals. Energy supply remains as the most significant problem with the use of these units. Various schemes are presently under investigation to remedy this situation, ranging from the use of implantable rechargeable batteries to the use of radioactive materials.
Synthesis and characterization of multi-functional nanoparticles possessing magnetic, up-conversion fluorescence and bio-affinity properties (2004)

Multi-functional nanoparticles possessing magnetic, up-conversion fluorescence and bio-affinity properties were synthesized and characterized. The particles have a core/shell structure. Iron oxide nanoparticles of 5–15 nm diameter were synthesized as the magnetic core. The core was covered with ytterbium and erbium co-doped sodium yttrium fluoride (NaYF4:Yb,Er), an efficient infrared-to-visible up-conversion phosphor. The phosphor shell was prepared by co-precipitation of the rare-earth metal salts with fluoride in the presence of EDTA and the magnetic nanoparticle. After the magnetic/fluorescent hybrid particle was coated with SiO2 and activated with glutaraldehyde, streptavidin was immobilized on the particle. The magnetic/fluorescent nanoparticles were found by transmission electron microscopy to be well-dispersed spherical particles with an average diameter of 68 nm. Both energy dispersive X-ray microanalysis and X-ray fluorescence spectra revealed the existence of iron in the particle. Measurements performed on a vibrating sample magnetometer obtained a strong magnetic response for the particle and fluorescence measurements demonstrated its up-conversion property. X-Ray diffraction analysis suggests the phosphor shell has the same structure as the pure NaYF4:Yb,Er nanoparticles we prepared in a previous study (G. S. Yi, H. C. Lu, S. Y. Zhao, Y. Ge, W. J. Yang, L. H. Guo, D. P. Chen and J. Cheng, submitted). Streptavidin-coated magnetic/fluorescent particles were found to bind specifically to a glass slide spotted with biotinylated IgG and emit up-conversion fluorescence, confirming the successful coating of the protein and retention of its optical activity and bio-affinity.
Endostatin Causes G1 Arrest of Endothelial Cells through Inhibition of Cyclin D1 (2002)

Endostatin, a type XVIII collagen fragment, is a potent antiangiogenic molecule that inhibits endothelial cell migration, promotes apoptosis, and induces cell cycle arrest in vitro. We have investigated the mechanism by which endostatin causes G(1) arrest in endothelial cells. Endostatin decreased the hyperphosphorylated retinoblastoma gene product and down-regulated cyclin D1 mRNA and protein. Importantly, endostatin was unable to arrest cyclin D1 overexpressing endothelial cells, suggesting that cyclin D1 is a critical target for endostatin action. Next, we analyzed cyclin D1 promoter activity in endothelial cells and found that endostatin down-regulated the cyclin D1 promoter. Using a series of deletion and mutant promoter constructs, we identified the LEF1 site in the cyclin D1 promoter as essential for the inhibitory effect of endostatin. Finally, we showed that endostatin can repress cyclin D1 promoter activity in cells over-expressing beta-catenin but not in cells over-expressing a transcriptional activator that functions through the LEF1 site and is insensitive to beta-catenin. Collectively, our data pointed to a role for cyclin D1, and in particular, transcription through the LEF1 site as critical for endostatin action in vitro and suggest that beta-catenin is a target for endostatin.
Isolation of a high-affinity stable single-chain Fv specific for mesothelin from DNA-immunized mice by phage display and construction of a recombinant immunotoxin with anti-tumor activity (1998)

Mesothelin is a differentiation antigen present on the surface of ovarian cancers, mesotheliomas, and several other types of human cancers. Because among normal tissues, mesothelin is present only on mesothelial cells, it represents a good target for antibody-mediated delivery of cytotoxic agents. In the present study mice were immunized with an eukaryotic expression vector coding for mesothelin. When high serum antibody titers were obtained, a phage display library was made from the splenic mRNA of these mice. After three rounds of panning on recombinant mesothelin, a single-chain Fv (scFv)-displaying phage was selected that bound specifically to recombinant mesothelin and mesothelin-positive cells. The scFv was used to construct an immunotoxin by genetically fusing it with a truncated mutant of Pseudomonas exotoxin A. The purified immunotoxin binds mesothelin with high affinity (Kd 11 nm), is stable for over 40 hr at 37 degrees C and is very cytotoxic to cells expressing mesothelin. It also produces regressions of tumors expressing mesothelin. This combination of selective cytotoxicity, high activity, and stability makes the immunotoxin a good candidate for development as a therapeutic agent. This work also shows that DNA immunization can be used to isolate and clone antibodies against epitopes present on human proteins in their native conformation.
Identification of 315 genes essential for early zebrafish development (2004)

We completed a large insertional mutagenesis screen in zebrafish to identify genes essential for embryonic and early larval development. We isolated 525 mutants, representing lesions in approximately 390 different genes, and we cloned the majority of these. Here we describe 315 mutants and the corresponding genes. Our data suggest that there are roughly 1,400 embryonic-essential genes in the fish. Thus, we have mutations in approximately 25% of these genes and have cloned approximately 22% of them. Re-screens of our collection to identify mutants with specific developmental defects suggest that approximately 50 genes are essential for the development of some individual organs or cell types. Seventy-two percent of the embryonic-essential fish genes have homologues in yeast, 93% have homologues in invertebrates (fly or worm), and 99% have homologues in human. Yeast and worm orthologues of genes that are essential for early zebrafish development have a strong tendency to be essential for viability in yeast and for embryonic development in the worm. Thus, the trait of being a genetically essential gene is conserved in evolution. This mutant collection should be a valuable resource for diverse studies of cell and developmental biology.
Homologous recombination in plant cells is enhanced byin vivoinduction of double strand breaks into DNA by a site-specific endonuclease (1993)

Induction of double strand breaks (DSBs) is coupled to meiotic and mitotic recombination in yeast. We show that also in a higher eukaryote induction of DSBs is directly correlated with a strong enhancement of recombination frequencies. We cotransfected Nicotiana plumbaginifolia protoplasts with a plasmid carrying a synthetic I-SceI gene, coding for a highly sequence specific endonuclease, together with recombination substrates carrying an I-SceI-site adjacent to their homologous sequences. We measured efficiencies of extrachromosomal recombination, using a well established transient beta-glucuronidase (GUS) assay. GUS enzyme activities were strongly increased when a plasmid carrying the I-SceI gene in sense but not in antisense orientation with respect to the promoter was included in the transfections. The in vivo induced DSBs were detected in the recombination substrates by Southern blotting, demonstrating that the yeast enzyme is functional in plant cells. At high ratios of transfected I-SceI-genes to I-SceI-sites the majority of the I-SceI-sites in the recombination substrates are cleaved, indicating that the induction of the DSBs is the rate limiting step in the described recombination reaction. These results imply that in vivo induction of transient breaks at specific sites in the plant genome could allow foreign DNA to be targeted to these sites via homologous recombination.
HIV-1 Subtypes B and C Tat Differentially Impact Synaptic Plasticity Expression and Implicates HIV-Associated Neurocognitive Disorders&#167; (2015)

Earlier studies have established that infection with HIV-1 subtypes (clades) might differentially influence the neuropathogenesis of HIV-1-associated neurocognitive dysfunction (HAND). HIV-1 Trans activator of transcription protein (Tat) is of considerable significance and plays a major role in the central nervous system (CNS) dysfunction. However, these HIV-1 clades exert diverse cellular effects that leads to neuropathogenic dysfunction has not been well established. We hypothesized that the HIV-1 clade B and clade C Tat proteins effect synaptic plasticity expression in neuroblastoma cells (SK-N-MC) by diverse methods, and accordingly modulates the development of HAND. In the present study, we have analyzed important and highly expressed 84 key human synaptic plasticity genes expression which differentially impact in clade B and clade C Tat treated SK-N-MC cells using RT(2) Profile PCR Array human Synaptic Plasticity kit. Observed results demonstrate that out of 84 key synaptic plasticity genes, 36 and 25 synaptic genes were substantially (≥3 fold) up-regulated and 5 and 5 genes considerably (≥3 fold) down-regulated in clade B and clade C Tat treated cells, respectively, compared to the control SK-N-MC. We have also estimated the levels of glutamine and glutamate in HIV-1 clade B and C Tat exposed SK-N-MC cells compared to untreated cells. Our results indicate that levels of glutamate, glutamine and expression of synaptic plasticity genes were highly dysregulated by HIV-1 clade B Tat compared to clade C Tat in SK-N-MC cells. In summary, this study suggests that clade B Tat substantially potentiates neuronal toxicity and further dysregulated synaptic plasticity genes in SK-N-MC may contribute to the severe neuropathogenesis linked with HAND.
Crystal Structures of the Binary and Ternary Complexes of 7α-Hydroxysteroid Dehydrogenase from Escherichia coli, (1996)

7 alpha-Hydroxysteroid dehydrogenase (7 alpha-HSDH;1 EC 1.1.1.159) is an NAD+-dependent oxidoreductase belonging to the short-chain dehydrogenase/reductase (SDR) 1 family. It catalyzes the dehydrogenation of a hydroxyl group at position 7 of the steroid skeleton of bile acids. The crystal structure of the binary (complexed with NAD+) complex of 7 alpha-HSDH has been solved at 2.3 A resolution by the multiple isomorphous replacement method. The structure of the ternary complex [the enzyme complexed with NADH, 7-oxoglycochenodeoxycholic acid (as a reaction product), and possibly partially glycochenodeoxycholic acid (as a substrate)] has been determined by a difference Fourier method at 1.8 A resolution. The enzyme 7 alpha-HSDH is an alpha/beta doubly wound protein having a Rossmann-fold domain for NAD (H) binding. Upon substrate binding, large conformation changes occur at the substrate binding loop (between the beta F strand and alpha G helix) and the C-terminal segment (residues 250-255). The variable amino acid sequences of the substrate-binding loop appear to be responsible for the wide variety of substrate specificities observed among the enzymes of the SDR family. The crystal structure of the ternary complex of 7 alpha-HSDH, which is the only structure available as the ternary complex among the enzymes of the SDR family, indicates that the highly conserved Tyr159 and Ser146 residues most probably directly interact with the hydroxyl group of the substrates although this observation cannot be definite due to an insufficiently characterized nature of the ternary complex. The strictly conserved Lys163 is hydrogen-bonded to both the 2'- and 3'-hydroxyl groups of the nicotinamide ribose of NAD(H). We propose a new catalytic mechanism possibly common to all the enzymes belonging to the SDR family in which a tyrosine residue (Tyr159) acts as a catalytic base and a serine residue (Ser146) plays a subsidiary role of stabilizing substrate binding.
Depression of Cellular Immunity After Major Injury (1986)

This study examined a group of surgical patients with respect to the ability of their peripheral blood mononuclear cells to respond to phytohemagglutinin (PHA). Depression of the PHA response of more than 30% below baseline five to seven days after injury was found in 11 of 19 patients, and eight of them developed infectious complications. The addition of indomethacin to in vitro cultures resulted in an average enhancement of the PHA response of 37% baseline. Improvement at five to seven days with in vitro indomethacin was from 34% to 74% in infected patients. These data suggest that major injury can lead to depression of the PHA response, which correlates with the subsequent development of infectious complications. Indomethacin in vitro seems to be able to reverse or decrease this immunologic defect and deserves further study.
Expression Cloning of Human Globoside Synthase cDNAs (2000)

By using a eukaryocytic cell expression cloning system, we have isolated cDNAs of the globoside synthase (beta1, 3-N-acetylgalactosaminyltransferase) gene. Mouse fibroblast L cells transfected with SV40 large T antigen and previously cloned Gb3/CD77 synthase cDNAs were co-transfected with a cDNA library prepared from mRNA from human kidney together with Forssman synthase cDNA, and Forssman antigen-positive cells were panned using an anti-Forssman monoclonal antibody. The isolated cDNAs contained a single open reading frame predicting a type II membrane protein with 351 amino acids. Surprisingly, the cDNA clones turned out to be identical with previously reported beta3Gal-T3, which had been cloned by sequence homology with other galactosyltransferases. Substrate specificity analysis with extracts from cDNA-transfected L cells confirmed that the gene product was actually beta1, 3-N-acetylgalactosaminyltransferase that specifically catalyzes the transfer of N-acetylgalactosamine onto globotriaosylceramide. Results of TLC immunostaining of neutral glycolipids from the cDNA-transfected cells also supported the identity of the newly synthesized component as globoside. The results show that glycosyltransferases apparently belonging to a single glycosyltransferase family do not necessarily catalyze reactions utilizing the same acceptor or even the same sugar donor. The globoside synthase gene was expressed in many tissues, such as heart, brain, testis, etc. We propose the designation beta3GalNAc-T1 for the cloned globoside synthase gene.
N-acetylcolchinol O-methyl ether and thiocolchicine, potent analogs of colchicine modified in the C ring. Evaluation of the mechanistic basis for their enhanced biological properties. (1990)

Two colchicine analogs with modifications only in the C ring are better inhibitors than colchicine of cell growth and tubulin polymerization. Radiolabeled thiocolchicine (with a thiomethyl instead of a methoxy group at position C-10) and N-acetylcolchinol O-methyl ether (NCME) (with a methoxy-substituted benzenoid instead of the methoxy-substituted tropone C ring) were prepared for comparison with colchicine. Scatchard analysis indicated a single binding site with KD values of 1.0-2.3 microM. Thiocolchicine was bound 2-4 times as rapidly as colchicine, but the activation energies of the reactions were nearly identical (18 kcal/mol for colchicine, 20 kcal/mol for thiocolchicine). NCME bound to tubulin in a biphasic reaction. The faster phase was 60 times as fast as colchicine binding at 37 degrees C, and a substantial reaction occurred at 0 degrees C. The rate of the faster phase of NCME binding changed relatively little as a function of temperature, so the activation energy was only 7.0 kcal/mol. Dissociation reactions were also evaluated, and at 37 degrees C the half-lives of the tubulin-drug complexes were 11 min for NCME, 24 h for thiocolchicine, and 27 h for colchicine. Relative dissociation rates as a function of temperature varied little among the drug complexes. Activation energies for the dissociation reactions were 30 kcal/mol for thiocolchicine, 27 kcal/mol for NCME, and 24 kcal/mol for colchicine. Comparison of the activation energies of association and dissociation yielded free energies for the binding reactions of -20 kcal/mol for NCME, -10 kcal/mol for thiocolchicine, and -6 kcal/mol for colchicine. The greater effectiveness of NCME and thiocolchicine as compared with colchicine in biological assays probably derives from their more rapid binding to tubulin and the lower free energies of their binding reactions.
Chromoendoscopy and magnification endoscopy in the colon (1999)

Gastrointest Endosc 1999;49:S45-9.
Gamut Constrained Illuminant Estimation (2003)

This paper presents a novel solution to the illuminant estimation problem: the problem of how, given an image of a scene taken under an unknown illuminant, we can recover an estimate of that light. The work is founded on previous gamut mapping solutions to the problem which solve for a scene illuminant by determining the set of diagonal mappings which take image data captured under an unknown light to a gamut of reference colours taken under a known light. Unfortunately a diagonal model is not always a valid model of illumination change and so previous approaches sometimes return a null solution. In addition, previous methods are difficult to implement. We address these problems by recasting the problem as one of illuminant classification: we define a priori a set of plausible lights thus ensuring that a scene illuminant estimate will always be found. A plausible light is represented by the gamut of colours observable under it and the illuminant in an image is classified by determining the plausible light whose gamut is most consistent with the image data. We show that this step (the main computational burden of the algorithm) can be performed simply, quickly, and efficiently by means of a non-negative least-squares optimisation. We report results on a large set of real images which show that it provides excellent illuminant estimation, outperforming previous algorithms.
n&ndash;3 Polyunsaturated Fatty Acid Supplementation (Pikasol&reg;) in Men with Moderate and Severe Hypertriglyceridaemia: A Dose-Response Study (1992)

The effect of n-3 fatty acids in 11 men with hypertriglyceridaemia was investigated. The subjects were given daily supplements with three different doses of n-3 fatty acids for 8-week periods. The supplements given were 2, 4 and 9 g of n-3 fatty acids/day, respectively. Total cholesterol, triglycerides and the ratio of total cholesterol to HDL-cholesterol significantly decreased with all three doses in a dose-dependent way. HDL-cholesterol increased in a dose-dependent fashion, while apolipoproteins A1 and B were unaltered by the supplements apart from a small increase in apolipoprotein A1 after the lowest dose of n-3 fatty acids. The greatest effect was observed after 2 g of n-3 fatty acids/day.
Automated extra pipeline analysis of applications mapped to Xilinx UltraScale+ FPGAs (2016)

This paper describes the methodology and algorithms behind extra pipeline analysis tools released in the Xilinx Vivado Design Suite version 2015.3. Extra pipelining is one of the most effective ways to improve performance of FPGA applications. Manual pipelining, however, often requires significant efforts from FPGA designers who need to explore various changes in the RTL and re-run the flow iteratively. The automatic pipelining approach described in this paper, in contrast, allows FPGA users to explore latency vs. performance trade-offs of their designs before investing time and effort into modifying RTL. We describe algorithms behind these tools which use simple cut heuristics to maximize performance improvement while minimizing additional latency and register overhead. To demonstrate the effectiveness of the proposed approach, we analyse a set of 93 commercial FPGA applications and IP blocks mapped to Xilinx UltraScale+ and UltraScale generations of FPGAs. The results show that extra pipelining can provide from 18% to 29% potential Fmax improvement on average. It also shows that the distribution of improvements is bimodal, with almost half of benchmark suite designs showing no improvement due to the presence of large loops. Finally, we demonstrate that highly-pipelined designs map well to UltraScale+ and UltraScale FPGA architectures. Our approach demonstrates 19% and 20% Fmax improvement potential for the UltraScale+ and UltraScale architectures respectively, with the majority of applications reaching their loop limit through pipelining.