gebhart/patrepeval huggingface dataset:
The House that Rex Built (2009)

This Founders Day address was given to the J. Reuben Clark Law Society at Little America Hotel in Salt Lake City on September 14, 2006.
Mutation in HBV RNA-dependent DNA polymerase confers resistance to lamivudine in vivo (1996)

The (-) enantiomer of 3'-thiacytidine (lamivudine) has been found to be a potent inhibitor of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) replication. Mutation of methionine to valine or isoleucine at the YMDD (tyrosine, methionine, aspartate, aspartate) motif of the HIV reverse transcriptase has been shown to be responsible for lamivudine resistance in HIV. The hepadnaviruses also have the YMDD motif in their DNA polymerase. Therefore, it is possible that hepadnaviruses could develop lamivudine resistance by a similar mutation at this motif. We analyzed the HBV from a liver transplantation patient who developed recurrent HBV viremia during lamivudine treatment. The polymerase gene was amplified by polymerase chain reaction (PCR), and the region coding for the YMDD motif was sequenced. The pretreatment HBV sequence coded for YMDD, while the lamivudine-resistant mutant HBV coded for YIDD (tyrosine, isoleucine, aspartate, aspartate). With the documented changes in the YMDD motif of lamivudine-resistant HIV, it is likely that the methionine-to- isoleucine mutation in the YMDD motif of the HBV polymerase contributes significantly to the lamivudine-resistance of HBV isolated from this patient. (Hepatology 1996 Sep;24(3):714-7)
Plasticity of endothelial cells during arterial-venous differentiation in the avian embryo (2001)

Remodeling of the primary vascular system of the embryo into arteries and veins has long been thought to depend largely on the influence of hemodynamic forces. This view was recently challenged by the discovery of several molecules specifically expressed by arterial or venous endothelial cells. We here analysed the expression of neuropilin-1 and TIE2, two transmembrane receptors known to play a role in vascular development. In birds, neuropilin-1 was expressed by arterial endothelium and wall cells, but absent from veins. TIE2 was strongly expressed in embryonic veins, but only weakly transcribed in most arteries. To examine whether endothelial cells are committed to an arterial or venous fate once they express these specific receptors, we constructed quail-chick chimeras. The dorsal aorta, carotid artery and the cardinal and jugular veins were isolated together with the vessel wall from quail embryos between embryonic day 2 to 15 and grafted into the coelom of chick hosts. Until embryonic day 7, all grafts yielded endothelial cells that colonized both host arteries and veins. After embryonic day 7, endothelial plasticity was progressively lost and from embryonic day 11 grafts of arteries yielded endothelial cells that colonized only chick arteries and rarely reached the host veins, while grafts of jugular veins colonized mainly host veins. When isolated from the vessel wall, quail aortic endothelial cells from embryonic day 11 embryos were able to colonize both host arteries and veins. Our results show that despite the expression of arterial or venous markers the endothelium remains plastic with regard to arterial-venous differentiation until late in embryonic development and point to a role for the vessel wall in endothelial plasticity and vessel identity.
GENEVESTIGATOR. Arabidopsis Microarray Database and Analysis Toolbox (2004)

High-throughput gene expression analysis has become a frequent and powerful research tool in biology. At present, however, few software applications have been developed for biologists to query large microarray gene expression databases using a Web-browser interface. We present GENEVESTIGATOR, a database and Web-browser data mining interface for Affymetrix GeneChip data. Users can query the database to retrieve the expression patterns of individual genes throughout chosen environmental conditions, growth stages, or organs. Reversely, mining tools allow users to identify genes specifically expressed during selected stresses, growth stages, or in particular organs. Using GENEVESTIGATOR, the gene expression profiles of more than 22,000 Arabidopsis genes can be obtained, including those of 10,600 currently uncharacterized genes. The objective of this software application is to direct gene functional discovery and design of new experiments by providing plant biologists with contextual information on the expression of genes. The database and analysis toolbox is available as a community resource at https://www.genevestigator.ethz.ch.
Ehrlichia chaffeensis, a new species associated with human ehrlichiosis (1991)

The bacterial 16S rRNA genes from blood samples of two patients with human ehrlichiosis and from an isolate recovered from one of the patients were amplified by using the polymerase chain reaction. The amplimers were then cloned and sequenced. The 16S rRNA gene sequence was also determined for Ehrlichia canis (two strains), E. equi, E. phagocytophila (two strains), and E. sennetsu (two strains). These sequences, along with a previously published 16S rRNA gene sequence of E. risticii, were compared. The 16S rRNA gene sequences were identical for all three sources of the human ehrlichiosis agent. The sequence comparisons indicate that the human ehrlichiosis agent is a new species most closely related to E. canis (98.2%) and more distantly related to other Ehrlichia spp. We propose that this species be named Ehrlichia chaffeensis sp. nov., with the Arkansas strain as the type strain.
A Simple, Clinical Assay to Evaluate The Acrosin Activity of Human Spermatozoa (1989)

Acrosin, a sperm-specific acrosomal proteinase, has an essential role in the fertilization process. Low levels of acrosin appear to be associated with subfertility and infertility, and the acrosin activity of spermatozoa may potentially be a useful indicator of semen quality. The standard acrosin tests employed by research laboratories are too complicated and/or time consuming for clinical use; therefore, a simple assay has been developed to assess total acrosin activity (acrosin and activatable proacrosin). To perform the test, liquefied semen is centrifuged over Ficoll, the washed sperm pellet is suspended in a detergent (Triton X-100)-substrate (N-alpha-benzoyl-DL-arginine p-nitroanilide) buffer, pH. 8.0, and the amidase activity is determined spectrophotometrically after a 3-hour incubation period. Amidase activity can be inhibited with benzamidine, indicating that the activity is primarily or entirely due to acrosin. The absence of detergent in the incubation medium results in greatly reduced activity. The assay is repeatable, linear with increasing sperm concentration, sensitive to a lower limit of 2 x 10(6) spermatozoa, and the results correspond to those obtained with a standard acrosin extraction and assay technique. Storage of ejaculates at 3 to 6 C or at 22 to 24 C for 24 hours does not affect the acrosin activity significantly but much higher temperatures can cause a loss of activity. Freezing ejaculates results in a large decrease in sperm acrosin activity. Leukocytes show minimal activity in the assay. Sperm populations prepared by a swim-up procedure average approximately a 2-fold higher acrosin activity than the original ejaculates. Preliminary experiments indicate that the average sperm acrosin activity of ejaculates whose spermatozoa successfully fertilize human eggs in vitro is significantly higher than those that do not fertilize eggs.
Enhanced responsiveness of endothelium in the growing/motile state to tumor necrosis factor/cachectin. (1989)

Some in vivo observations have suggested that growing or perturbed endothelium, such as that which occurs during angiogenesis, is more sensitive to the action of cytokines (TNF/cachectin, TNF, or IL-1) than normal quiescent endothelial cells. This led us to examine the responsiveness of endothelium to TNF as a function of the growth/motile state of the cell. TNF-induced modulation of endothelial cell surface coagulant function was half-maximal at a concentration of approximately 0.1 nM in subconfluent cultures, whereas 1-2 nM was required for the same effect in postconfluent cultures. Perturbation of endothelial cell shape/cytoskeleton was similarly more sensitive to TNF in subconfluent cultures. Consistent with these results, radioligand binding studies demonstrated high affinity TNF binding sites, Kd approximately 0.1 nM on subconfluent cultures, whereas only lower affinity sites (Kd approximately 1.8 nM) were detected on postconfluent cultures. The mechanisms underlying this change in the affinity of endothelium for TNF were studied in four settings. Crosslinking experiments with 125I-TNF and endothelium showed additional bands corresponding to Mr approximately 66,000 and approximately 84,000 with subconfluent cultures that were not observed with postconfluent cultures. Experiments with X-irradiated endothelium, whose growth but not motility was blocked, indicated that proliferation was not required for induction of high affinity TNF sites. Postconfluent endothelium, triggered to enter the proliferative cycle by microbutuble poisons, expressed high affinity TNF binding sites together with changes in cell shape/cytoskeleton well before their entry into S phase. Using wounded postconfluent monolayers, cells that migrated into the wound and those close to the wound edge displayed enhanced TNF binding and modulation of coagulant properties. These results suggest a model for targetting TNF action within the vasculature; regulation of high affinity endothelial cell binding sites can direct TNF to activated cells in particular parts of the vascular tree.
The Balance of Nuclear Import and Export Determines the Intracellular Distribution and Function of Tomato Heat Stress Transcription Factor HsfA2 (2001)

Tomato heat stress transcription factor HsfA2 is a shuttling protein with dominant cytoplasmic localization as a result of a nuclear import combined with an efficient export. Besides the nuclear localization signal (NLS) adjacent to the oligomerization domain, a C-terminal leucine-rich motif functions as a nuclear export signal (NES). Mutant forms of HsfA2 with a defective or an absent NES are nuclear proteins. The same is true for the wild-type HsfA2 if coexpressed with HsfA1 or in the presence of export inhibitor leptomycin B (LMB). Fusion of the NES domain of HsfA2 to HsfB1, which is a nuclear protein, caused export of the HsfB1-A2NES hybrid protein, and this effect was reversed by the addition of LMB. Due to the lack of background problems, Chinese hamster ovary (CHO) cells represent an excellent system for expression and functional analysis of tomato Hsfs. The results faithfully reflect the situation found in plant cells (tobacco protoplasts). The intriguing role of NLS and NES accessibility for the intracellular distribution of HsfA2 is underlined by the results of heat stress treatments of CHO cells (41 degrees C). Despite the fact that nuclear import and export are not markedly affected, HsfA2 remains completely cytoplasmic at 41 degrees C even in the presence of LMB. The temperature-dependent conformational transition of HsfA2 with shielding of the NLS evidently needs intramolecular interaction between the internal HR-A/B and the C-terminal HR-C regions. It is not observed with the HR oligomerization domain (HR-A/B region) deletion form of HsfA2 or in HsfA2-HsfA1 hetero-oligomers.
Interactions of gonococci with HeLa cells: attachment, detachment, replication, penetration, and the role of protein II (1986)

Colony variants of Neisseria gonorrhoeae differ in their interactions with eucaryotic cells. When gonococci were cultivated with HeLa cell monolayers, the opacity phenotype (Op) became increasingly dominant in the subpopulation of organisms which adhered to the HeLa cells. Once bound, Op organisms displayed very low levels of detachment. Adherent Op gonococci exhibited generation times up to threefold greater than cultures containing gonococci in the absence of HeLa cells. In addition, the progeny of adherent Op organisms remained bound to the HeLa cell monolayer. Both piliated (P+) and transparent (Tr) colony types attached to HeLa cells, but their progeny were retained less efficiently. Gonococci bound to HeLa cells were subjected to the bactericidal action of fresh rat serum and approximately 0.5 to 2.5% survived, irrespective of their opacity or piliation phenotype. Incubation with gentamicin resulted in a 10- to 50-fold further reduction in viability. Pretreatment of HeLa cell monolayers with the microfilament-disrupting agent cytochalasin b diminished gonococcal survival in either serum or gentamicin by up to eightfold. In contrast, cytochalasin b treatment did not decrease survival of the commensal organism N. sicca. The data suggest that very few gonococci are completely interiorized and a small proportion of adherent gonococci are partially protected from the soluble-phase environment by HeLa cells.
Nucleotide sequence of the gene encoding the serotype-specific antigen of human (Wa) rotavirus: comparison with the homologous genes from simian SA11 and UK bovine rotaviruses (1984)

The nucleotide sequence of human (Wa) rotavirus genome segment 9, which encodes the serotype-specific antigen VP7, has been determined. Comparison of the deduced amino acid sequence of Wa VP7 protein to the sequences of simian SA11 and UK bovine VP7 proteins shows that the majority of the amino acid differences are clustered between amino acid residues 37 through 49, 65 through 75, 87 through 105, 122 through 126, 146 through 149, 178 through 181, and 208 through 242. A hydrophilicity profile of the three proteins reveals correlations between hydrophilic peaks, potentially antigenic determinants, and certain clusters of amino acid changes.
Design of wavelength-routed optical networks for circuit switched traffic (2002)

We consider the problem of routing and assignment of wavelength (RAW) in wavelength-routed optical networks. Given a set of requests for all-optical connections (or lightpaths), the problem is to find wavelength-continuous routes from the source nodes to their respective destination nodes. Since the number of wavelengths available per link is limited, lightpaths cannot be established between every source-destination node pairs. Moreover, a common wavelength might not be available on all the segments of a chosen route. Thus, routing and wavelength assignment are to be considered concurrently for the best possible performance. Several heuristic algorithms have already been proposed for the RAW problem, however, most of these algorithms are based on the traditional model of circuit-switched networks where the routing and wavelength assignment steps are decoupled. A new RAW scheme is developed which unifies the routing and wavelength assignment subproblems. This unified approach is found to yield significantly better solutions to the RAW problem than the earlier ones. The paper also introduces an analytical model for predicting the average number of lightpaths requests a given physical network can support.
Expression of vascular endothelial growth factor (VEGF) and its receptors in thyroid carcinomas of follicular origin: a potential autocrine loop (2005)

Our results highlight a previously undefined VEGF autocrine action in thyroid carcinomas which could play a crucial role in tumour cell survival and could represent a useful therapeutic target for thyroid tumours.
Quality of designs from an automatic logic generator (ALERT) (1970)

Automation of the design of computer logic has evoked wide-spread interest and activity. Nevertheless, detailed comparisons of automatically generated logic and manually prepared logic have not been made available.
Calcium regulation of growth and differentiation of normal human keratinocytes: Modulation of differentiation competence by stages of growth and extracellular calcium (1990)

In this study we examined the different aspects of the pathway leading to the differentiation of keratinocytes as a function of time in culture and calcium concentration of the culture medium. Human neonatal foreskin keratinocytes were grown in a serum-free, defined medium containing 0.07, 1.2, or 2.4 mM calcium and assayed for the rate of growth and protein synthesis, involucrin content, transglutaminase activity, and cornified envelope formation at preconfluent, confluent, and postconfluent stages of growth. We observed that keratinocytes grown to postconfluence in all calcium concentrations showed an increased protein/DNA ratio and an increased rate of membrane-associated protein synthesis. Extracellular calcium concentrations did not have a clear influence on these parameters. However, preconfluent and confluent keratinocytes grown in 0.07 mM calcium showed markedly retarded differentiation at all steps, i.e., involucrin synthesis, transglutaminase activity, and cornified envelope formation. Within 1 week after achieving confluence, these keratinocytes began synthesizing involucrin and transglutaminase and developed the ability to form cornified envelopes. Cells grown in 1.2 and 2.4 mM calcium synthesized involucrin and transglutaminase prior to confluence and were fully competent to form cornified envelopes by confluence. Thus external calcium-regulated keratinocyte differentiation is not an all or none phenomenon, but rather it is the rate at which keratinocytes differentiate that is controlled by calcium. We conclude that either or both higher extracellular calcium concentration and the achievement of cell-cell contacts lead to a coordinate increase of at least two precursors--involucrin content and transglutaminase activity--required for cornified envelope formation. We speculate that a critical level of cytosolic calcium, achieved by increased extracellular calcium or by achievement of intercellular communication established by cell-cell contact, may trigger mechanisms required for initiation of keratinocyte differentiation.
Column Bioleaching at Room Temperature (2010)

A column bioleaching experiment at room temperature with no addition of sulfuric acid was effectively carried out to leach the valuable elements from pyrite, which is common mine waste. The Fe concentration of pyrite leachate from bioleaching column was 14 times higher than that of the control leachate, and secondary minerals were not formed. The SO4 2- concentration of the pyrite leachate was 2.99 times higher. The XRD intensity of the (111), (200), (220), (311), (222), (230) and (321) planes of pyrite decreased, whereas the intensity of (210) and (211) increased after column bioleaching.
Production of L-dihydroxyphenylalanine in Escherichia coli with the tyrosine phenol-lyase gene cloned from Erwinia herbicola (1993)

The gene (tutA) encoding tyrosine phenol-lyase from Erwinia herbicola was cloned into Escherichia coli, and fusions to the lac and tac promoters were constructed. The enzyme was expressed at high levels in E. coli in the presence of isopropyl-beta-D-thiogalactopyranoside or lactose as an inducer. L-Dihydroxyphenylalanine was synthesized in high yield from catechol, pyruvate, and ammonia by induced cells.
Two Retroviral Entry Pathways Distinguished by Lipid Raft Association of the Viral Receptor and Differences in Viral Infectivity (2003)

The receptor "priming" model for entry of the retrovirus avian sarcoma and leukosis virus (ASLV) predicts that upon binding cell surface receptors, virions are endocytosed and trafficked to acidic endosomes where fusion occurs. To test this model directly, we have now followed subgroup A ASLV (ASLV-A) virions entering cells via either the transmembrane (TVA950) or glycophosphatidylinositol (GPI)-anchored (TVA800) forms of the cellular receptor. Our results suggest that viruses entering via these two forms of receptor are subjected to different intracellular fates, perhaps due to use of different endocytic trafficking pathways to access acidic fusion compartments. Kinetic analyses demonstrated that virus bound to TVA800 was taken up from the cell surface more slowly but then trafficked to the site of fusion more quickly than that entering via TVA950. Furthermore, transiently arresting virions within putative fusion compartments with NH4Cl led to a substantially greater decrease in the infectivity of virions using TVA950 than with those using TVA800. The increased infectivity of virions using TVA800 correlated with the localization of this receptor to lipid rafts, since this effect was abolished by pharmacological disruption of lipid rafts. Together these results suggest that, in the presence of NH4Cl, virus bound to the GPI-anchored receptor may utilize a lipid raft-dependent pathway to accumulate within a fusion compartment where it is more stable than if it enters via the transmembrane receptor. The TVA800/ASLV-A system should prove useful for the molecular analysis of lipid raft-dependent endocytosis and may provide a tool for the biochemical dissection of the poorly understood uncoating step of retroviral replication.
Sulfated polyanion inhibition of scrapie-associated PrP accumulation in cultured cells (1993)

The accumulation of an abnormal, protease-resistant form of the protein PrP (PrP-res) in hosts with scrapie and related transmissible spongiform encephalopathies appears to be important in disease pathogenesis. To gain insight into the mechanism of PrP-res accumulation and the in vivo antiscrapie activity of certain polyanions, we have studied effects of sulfated glycans on PrP metabolism in scrapie-infected neuroblastoma cells. Pentosan polysulfate, like the amyloid-binding dye Congo red, potently inhibited the accumulation of PrP-res in these cells without apparent effects on the metabolism of the normal isoform. The inhibition was due primarily to prevention of new PrP-res accumulation rather than destabilization of preexisting PrP-res. PrP-res accumulation remained depressed in the cultures after removal of the inhibitors. The activities of other sulfated glycans, nonsulfated polyanions, dextran, and DEAE-dextran were compared with those of pentosan polysulfate and Congo red. This comparison provided evidence that the density of sulfation and molecular size are factors influencing anti-PrP-res activity of sulfated glycans. The relative potencies of these compounds corresponded well with their previously determined antiscrapie activities in vivo, suggesting that the prophylactic effects of sulfated polyanions may be due to inhibition of PrP-res accumulation. Since PrP-res amyloid is known to contain sulfated glycosaminoglycans, we reason that these inhibitors may competitively block an interaction between PrP and endogenous glycosaminoglycans that is essential for its accumulation in a protease-resistant, potentially amyloidogenic state.
Benchmark Handbook: For Database and Transaction Processing Systems (1992)

A practical guide that offers the reader a comprehensive view of benchmarking for modern transaction processing and database systems. Much of the information is available for the first time. The handbook provides the tools to evaluate different systems, different software products on a single machine, and different machines within a single product family.