gebhart/patrepeval huggingface dataset:
Molecular Cloning and Expression of Human and Mouse Tyrosylprotein Sulfotransferase-2 and a Tyrosylprotein Sulfotransferase Homologue in Caenorhabditis elegans (1998)

Tyrosine O-sulfation, a common post-translational modification in eukaryotes, is mediated by Golgi enzymes that catalyze the transfer of the sulfuryl group from 3'-phosphoadenosine 5'-phosphosulfate to tyrosine residues in polypeptides. We recently isolated cDNAs encoding human and mouse tyrosylprotein sulfotransferase-1 (Ouyang, Y. B., Lane, W. S., and Moore, K. L. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 2896-2901). Here we report the isolation of cDNAs encoding a second tyrosylprotein sulfotransferase (TPST), designated TPST-2. The human and mouse TPST-2 cDNAs predict type II transmembrane proteins of 377 and 376 amino acid residues, respectively. The cDNAs encode functional N-glycosylated enzymes when expressed in mammalian cells. In addition, preliminary analysis indicates that TPST-1 and TPST-2 have distinct specificities toward peptide substrates. The human TPST-2 gene is on chromosome 22q12.1, and the mouse gene is in the central region of chromosome 5. We have also identified a cDNA that encodes a TPST in the nematode Caenorhabditis elegans that maps to the right arm of chromosome III. Thus, we have identified two new members of a class of membrane-bound sulfotransferases that catalyze tyrosine O-sulfation. These enzymes may catalyze tyrosine O-sulfation of a variety of protein substrates involved in diverse physiologic functions.
Physiological fIXa Activation Involves a Cooperative Conformational Rearrangement of the 99-Loop (2003)

Coagulation factor IXa (fIXa) plays a central role in the coagulation cascade. Enzymatically, fIXa is characterized by its very low amidolytic activity that is not improved in the presence of cofactor, factor VIIIa (fVIIIa), distinguishing fIXa from all other coagulation factors. Activation of the fIXa-fVIIIa complex requires its macromolecular substrate, factor X (fX). The 99-loop positioned near the active site partly accounts for the poor activity of fIXa because it adopts a conformation that interferes with canonical substrate binding in S2-S4. Here we show that residues Lys-98 and Tyr-99 are critically linked to the amidolytic properties of fIXa. Exchange of Tyr-99 with smaller residues resulted not only in an overall decreased activity but also in impaired binding in S1. Replacement of Lys-98 with smaller and uncharged residues increased activity. Simultaneous mutagenesis of Lys-98, Tyr-177, and Tyr-94 produced an enzyme with 7000-fold increased activity and altered specificity. This triple mutant probably mimics the conformational changes that are physiologically induced by cofactor and substrate binding. It therefore provides a cooperative two-step activation model for fIXa. Tyr-177 locks the 99-loop in an inactive conformation which, in the physiologic complex, is released by cofactor fVIIIa. FX is then able to rearrange the unlocked 99-loop and subsequently binds to the active site cleft.
[Expression of human endogenous retroviruses in rheumatoid arthritis]. (1994)

The genomes of all organisms, from yeast to humans, contain thousands of endogenous retroviruses (ERVs) and ERVs are transmitted vertically through germ cells as provirus. In recent studies, it has been reported that some ERVs have important immunologic effects and are associated with autoimmune diseases in several animals. However, despite many years of investigation in human, physiological or pathological roles for ERVs remain unknown. In this study we examined whether the pathogenesis of rheumatoid arthritis (RA) was associated with human ERVs; ERV3 and lambda 4-1, which retain open reading frames (ORF) and could make proteins. We demonstrated that ERV3 and lambda 4-1 were expressed on synoviocytes and peripheral blood mononuclear cells (PBMCs) in RA patients by Northern blot analysis. But the expression was indeed heterogenous: RA patients showed various expression levels of ERV3 and lambda 4-1, which were independent of clinical activities and kinds of used drugs. mRNAs of ERV3 and lambda 4-1 were also expressed in PBMCs of healthy volunteers. We detected a 4.2 kb transcript of lambda 4-1 in synoviocytes and PBMCs which was not expressed in placentas, suggesting a unique protein might be produced in synoviocytes and PBMCs compared to placentas. In order to examine regulatory mechanisms for expression of human ERVs, we treated cultured synoviocytes and human kidney endothelial cells (hKEC) with various cytokines. By interleukin-1 beta (IL-1 beta) treatment, ERV3 expression in synoviocytes was not altered, but that in hKEC increased and correlated with IL-6 expression. Although ERV3 and lambda 4-1 expression may not be directly associated with the pathogenesis of RA, the possibility still exists that some of many ERVs, which are integrated into human genomes, may have causative roles in RA.
CD8 Cell Division Maintaining Cytotoxic Memory Occurs Predominantly in the Bone Marrow (2005)

Long-term persistence of Ag-experienced CD8 cells, a class of T lymphocytes with cytotoxic function, contributes to immunological memory against intracellular pathogens. After Ag clearance, memory CD8 cells are maintained over time by a slow proliferation, primarily cytokine driven. In this article, we show that the bone marrow (BM) is the crucial organ where such basal division of memory CD8 cells occurs. BM memory CD8 cells contain a higher percentage of proliferating cells than their corresponding cells in either spleen or lymph nodes from C57BL/6 mice. This occurs both in the case of memory-phenotype CD44(high) CD8 cells and in the case of Ag-specific memory CD8 cells. Importantly, the absolute number of Ag-specific memory CD8 cells dividing in the BM largely exceeds that in spleen, lymph nodes, liver, and lung taken together. In the BM, Ag-specific memory CD8 cells express lower levels of CD127, i.e., the alpha-chain of IL-7R, than in either spleen or lymph nodes. We interpret these results as indirect evidence that Ag-specific memory CD8 cells receive proliferative signals by IL-7 and/or IL-15 in the BM and propose that the BM acts as a saturable "niche" for the Ag-independent proliferation of memory CD8 cells. Taken together, our novel findings indicate that the BM plays a relevant role in the maintenance of cytotoxic T cell memory, in addition to its previously described involvement in long-term Ab responses.
Abnormal protein tyrosine kinase gene expression during melanoma progression and metastasis (1995)

Protein tyrosine kinases have been implicated in tumor initiation and progression. Here we used Northern blotting to study expression of their genes in cultured normal melanocytes and 19 melanoma cell lines from different stages of tumor progression. We detected transcripts for 2 cytoplasmic (ABL and FES) and 6 receptor (ECK, ERB-B2, FGF-R4, IGFI-R, KDR and TIE) kinases but not for receptors RET or TRK-A. Genes for ECK, FGF-R4 and TIE were expressed ectopically in melanomas (not in normal melanocytes). Similarly, ECK protein was detected by immunoblotting in metastatic melanomas but not in normal melanocytes. ECK mRNA levels tended to increase again during late melanoma progression. ECK and TIE mRNAs were also detected in highly metastatic variant cells but not in the corresponding poorly metastatic parental lines. Conversely, FES and KDR gene expression was lost in most advanced primary and metastatic melanomas. These findings suggest positive and negative roles for specific tyrosine kinases during progression.
Supramolecular structure of lipopolysaccharide and free lipid A under physiological conditions as determined by synchrotron small‐angle X‐ray diffraction (1989)

Lipopolysaccharides, the major amphiphilic components of the outer leaflet of the outer membrane of Gram-negative bacteria, may assume various three-dimensional supramolecular structures depending on molecular properties (e.g. chemical structure) and on ambient conditions (e.g. temperature, concentration of divalent cations). We applied synchrotron small-angle X-ray diffraction to investigate the supramolecular structures of natural and synthetic Escherichia-coli-type lipid A, of lipid A from Salmonella minnesota, and of rough mutant lipopolysaccharides of E. coli and S. minnesota under physiological water content (greater than 90%) at different temperatures (20, 37, and 55 degrees C) and at different lipid/divalent cation molar ratios (20:1 to 1:1). We found that in the absence of divalent cations rough mutant lipopolysaccharide and free lipid A form unilamellar structures with the main reflections centered around 4.50 nm for free lipid A, 4.80 nm for Re lipopolysaccharide, and 5.90 nm for Rd1 lipopolysaccharide at 20 degrees C, i.e. below the beta----alpha acyl-chain-melting transition temperature. Above this temperature, the reflections are shifted to 4.30 nm for free lipid A (at 55 degrees C), 4.60 nm for Re lipopolysaccharide (at 37 degrees C), and to 5.50 nm for Rd1 lipopolysaccharide (at 37 degrees C). The addition of divalent cations leads (at lower concentrations, i.e. lipid/cation molar ratios 20:1 to 5:1) to sharper reflections expressing a higher state of order and to a shift of the center of the main reflections lying now at 5.10 nm for free lipid A, 6.40 nm for Re and 7.20 nm for Rd1 lipopolysaccharide at 20 degrees C. At higher concentrations of divalent cations (e.g. lipid/cation molar ratio 1:1), an increasing tendency to form nonlamellar, inverted cubic structures is observed which is indicated by the occurrence of another main periodicity and/or of reflections with spacing ratios 1: square root of 2, 1: square root of 3 of the main periodicity. The tendency to assume inverted cubic structures is only weakly pronounced for rough mutant lipopolysaccharides but dominant for free lipid A even at physiological temperature and divalent cation concentration.
The formalin test in the mouse: a parametric analysis of scoring properties (2000)

We investigated the scoring properties of the mouse formalin test using the time-sampling method recently developed for infant and adult rats. Formalin was injected under the plantar surface of one rear paw (10 microl, 1-8%), and pain behaviours (paw favouring, lifting and licking) and behavioural state were recorded. Correlational and regression analyses indicated that scores composed of combinations of all three pain behaviours, either summed or weighted, provided less variable indices of pain than licking alone. The maximum percent effect (MPE(50); i.e. pain behaviour 50% of the time) for the log formalin concentration-effect curves was 3-4% in both phases. Habituation to the test environment prior to testing did not alter the MPE(50)s, but slopes were lower in unhabituated mice, dramatically increasing the size of the confidence interval. Formalin dose-dependently reduced locomotion, rearing and sniffing in both the first phase and the early part of the second phase. The combination measures were sensitive to morphine (2-8 mg/kg), amphetamine (1-4 mg/kg), dipyrone (50-200 mg/kg), xylazine (0.25-1 mg/kg), and acepromazine (0.25-1 mg/kg), and resistant to diazepam (0.5-2 mg/kg), pimozide (0.05-0.25 mg/kg), pentobarbital (10 and 15 mg/kg) and indomethacin (2-8 mg/kg). Decreased pain was correlated with increased motor activity for morphine and amphetamine, and with decreased activity for xylazine and acepromazine; dipyrone and indomethacin did not alter activity levels.
The first practical method for asymmetric epoxidation (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe first practical method for asymmetric epoxidationTsutomu Katsuki and K. Barry SharplessCite this: J. Am. Chem. Soc. 1980, 102, 18, 5974–5976Publication Date (Print):August 1, 1980Publication History Published online1 May 2002Published inissue 1 August 1980https://pubs.acs.org/doi/10.1021/ja00538a077https://doi.org/10.1021/ja00538a077research-articleACS PublicationsRequest reuse permissionsArticle Views27024Altmetric-Citations2472LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Marching to the beat of Moore's Law (2006)

Area density scaling in integrated circuits, defined as transistor count per unit area, has followed the famous observation-cum-prediction by Gordon Moore for many generations. Known as "Moore's Law" which predicts density doubling every 18-24 month, it has provided all important synchronizing guidance and reference for tools and materials suppliers, IC manufacturers and their customers as to what minimal requirements their products and services need to meet to satisfy technical and financial expectations in support of the infrastructure required for the development and manufacturing of corresponding technology generation nodes. Multiple lithography solutions are usually under considerations for any given node. In general, three broad classes of solutions are considered: evolutionary - technology that is extension of existing technology infrastructure at similar or slightly higher cost and risk to schedule; revolutionary - technology that discards significant parts of the existing infrastructure at similar cost, higher risk to schedule but promises higher capability as compared to the evolutionary approach; and last but not least, disruptive - approach that as a rule promises similar or better capabilities, much lower cost and wholly unpredictable risk to schedule and products yields. This paper examines various lithography approaches, their respective merits against criteria of respective infrastructure availability, affordability and risk to IC manufacturer's schedules and strategy involved in developing and selecting best solution in an attempt to sort out key factors that will impact the decision on the lithography choice for large-scale manufacturing for the future technology nodes.
<title>Generalized adaptive median filters and their application in computed tomography</title> (1994)

A generalized adaptive median filter (GAMF) is introduced for more robust noise suppression and edge preservation in computed tomography. The GAMF employs a set of adaptive linear filters in conjunction with an adaptive median filter. Each linear filter is designed to preserve a feature in one orientation. The window sizes of these filters are adaptive to the local statistics. The output of the GAMF is selected from the linear filter output set that is closest to the adaptive median filter. This filter has been successfully utilized in the computed tomography to combat severe streaking artifacts resulting from excessive x-ray quantum noise. Its effectiveness has been demonstrated in phantom tests and clinical studies. In addition, little impact on system resolution can be observed.
Pathophysiology of Artificial Aqueous Drainage in Primate Eyes with Molteno Implants (1994)

Single-plate Molteno implants were installed in two stages in glaucomatous monkey eyes. This device shunts aqueous from the anterior chamber to periocular orbital tissues. The mechanism of aqueous filtration and absorption was explored using flow studies, fluorescently labeled microspheres and histological examination of tissues. Flow studies indicated that the capsule around the explant functions by a passive mechanism, shunting aqueous into the extracellular space. Outflow is proportional to capsule surface area. Latex microspheres (0.2 mum and smaller) passed freely through the capsule, giving the impression of an open sieve. The presence of microspheres in the episcleral wall of the capsule indicates that all surfaces contribute to filtration. A concentration gradient of particles in the extracapsular space, away from the bleb surface, suggests that the capsule itself limits filtration rate.
Leptin in hepatic fibrosis: Evidence for increased collagen production in stellate cells and lean littermates of ob/ob mice (2002)

Leptin is a 16-kd hormone that mediates a range of metabolic effects by using a transduction pathway from the long form of the leptin receptor, OB-R(L,) through Janus kinase-signal transducer and activator of transcription (Jak-Stat) signaling components. Leptin is produced by hepatic stellate cells (HSCs) but only following their "activation." Because activation of stellate cells is a central event in the fibrotic response to liver injury, we hypothesized that leptin may directly stimulate fibrogenesis in activated stellate cells via OB-R(L). We analyzed leptin receptors and their signaling partners in a stellate cell line (HSC-T6) as well as in primary stellate cell isolates. We also examined the effect of leptin on stellate cell expression of alpha(2)(I) collagen messenger RNA (mRNA) levels by ribonuclease protection analysis (RPA). Finally, we examined the role of leptin in in vivo fibrogenesis by inducing a wounding response in ob/ob mice, which lack functional leptin. HSC-T6 and culture-activated stellate cells expressed OB-R(L). Scatchard analysis verified specific binding of leptin to HSCs, with an association constant (K(d)) equal to 660 +/- 5.8 pmol/L. Exposure of HSCs to leptin resulted in significant increases in alpha(2)(I) collagen mRNA expression. Transient transfection with a promoter reporter construct showed a 3-fold increase in alpha(2)(I) collagen transgene activity. Leptin stimulated activation of Stat3 in activated HSCs. Finally, lean animals, but not ob/ob littermates, had significant fibrosis as assessed by picrosirius red staining and abundant alpha-smooth muscle actin staining. In conclusion, these results indicate that leptin is profibrogenic in activated HSCs and can signal via the Jak-Stat pathway. Up-regulation of leptin signaling in liver injury could contribute to enhanced fibrogenesis, particularly in states in which leptin levels are high.
The partial-occlusion effect (1996)

This study investigates human performance when using semitransparent tools in interactive 3D computer graphics environments. The article briefly reviews techniques for presenting depth information and examples of applying semitransparency in computer interface design. We hypothesize that when the user moves a semitransparent surface in a 3D environment, the “partial-occlusion” effect introduced through semitransparency acts as an effective cue in target localization—an essential component in many 3D interaction tasks. This hypothesis was tested in an experiment in which subjects were asked to capture dynamic targets (virtual fish) with two versions of a 3D box cursor, one with and one without semitransparent surfaces. Results showed that the partial-occlusion effect through semitransparency significantly improved users' performance in terms of trial completion time, error rate, and error magnitude in both monoscopic and stereoscopic displays. Subjective evaluations supported the conclusions drawn from performance measures. The experimental results and their implications are discussed, with emphasis on the relative, discrete nature of the partial-occlusion effect and on interactions between different depth cues. The article concludes with proposals of a few future research issues and applications of semitransparency in human-computer interaction.
Predicting leucine zipper structures from sequence (1996)

The leucine zipper structure is adopted by one family of the coiled coil proteins. Leucine zippers have a characteristic leucine repeat: Leu-X6-Leu-X6-Leu-X6-Liu (where X may be any residue). However, many sequences have the leucine repeat, but do not adopt the leucine zipper structure (we shall refer to these as non-zippers). We have found and analyzed residue pair patterns that allow one to identify correctly 90% of leucine zippers and 97% of non-zippers. Simpler analyses, based on the frequency of occurrence of residues at certain positions, specify, at most, 65% of zippers and 80-90% of non-zippers. Both short and long patterns contribute to the successful discrimination of leucine zippers from non-zippers. A number of these patterns involve hydrophobic residues that would be placed on the solvent-exposed surface of the helix, were the sequence to adopt a leucine zipper structure. Thus, an analysis of protein sequences has allowed us to improve discrimination between leucine zippers and non-zippers, and has provided some further insight into the physical factors influencing the leucine zipper structure.
Genetic Evidence for an Interaction between Human Immunodeficiency Virus Type 1 Matrix and α-Helix 2 of the gp41 Cytoplasmic Tail (2000)

The incorporation of envelope (Env) glycoproteins into virions is an essential step in the retroviral replication cycle. Lentiviruses, including human immunodeficiency virus type 1 (HIV-1), encode Env glycoproteins with unusually long cytoplasmic tails, the functions of which have not been fully elucidated. In this study, we examine the effects on virus replication of a number of mutations in a helical motif (alpha-helix 2) located near the center of the HIV-1 gp41 cytoplasmic tail. We find that, in T-cell lines, small deletions in this domain disrupt the incorporation of Env glycoproteins into virions and markedly impair virus infectivity. Through the analysis of viral revertants, we demonstrate that a single amino acid change (34VI) in the matrix domain of Gag reverses the Env incorporation and infectivity defect imposed by a small deletion near the C terminus of alpha-helix 2. These results provide genetic evidence, in the context of infected T cells, for an interaction between HIV-1 matrix and the gp41 cytoplasmic tail and identify domains of both proteins involved in this putative interaction.
Herpes Simplex Virus Type 2 in the United States, 1976 to 1994 (1997)

Since the late 1970s, the prevalence of HSV-2 infection has increased by 30 percent, and HSV-2 is now detectable in roughly one of five persons 12 years of age or older nationwide. Improvements in the prevention of HSV-2 infection are needed, particularly since genital ulcers may facilitate the transmission of the human immunodeficiency virus.
Crystal engineering of pharmaceutical co-crystals from polymorphic active pharmaceutical ingredients (2005)

The carboxylic acid-primary amide supramolecular heterosynthon is exploited for the generation of pharmaceutical co-crystals that contain two active pharmaceutical ingredients that are polymorphic in their pure forms.