gebhart/patrepeval huggingface dataset:
Binding of a Large Chondroitin Sulfate/Dermatan Sulfate Proteoglycan, Versican, to L-selectin, P-selectin, and CD44 (2000)

Here we show that a large chondroitin sulfate proteoglycan, versican, derived from a renal adenocarcinoma cell line ACHN, binds L-selectin, P-selectin, and CD44. The binding was mediated by the interaction of the chondroitin sulfate (CS) chain of versican with the carbohydrate-binding domain of L- and P-selectin and CD44. The binding of versican to L- and P-selectin was inhibited by CS B, CS E, and heparan sulfate (HS) but not by any other glycosaminoglycans tested. On the other hand, the binding to CD44 was inhibited by hyaluronic acid, chondroitin (CH), CS A, CS B, CS C, CS D, and CS E but not by HS or keratan sulfate. A cross-blocking study indicated that L- and P-selectin recognize close or overlapping sites on versican, whereas CD44 recognizes separate sites. We also show that soluble L- and P-selectin directly bind to immobilized CS B, CS E, and HS and that soluble CD44 directly binds to immobilized hyaluronic acid, CH, and all the CS chains examined. Consistent with these results, structural analysis showed that versican is modified with at least CS B and CS C. Thus, proteoglycans sufficiently modified with the appropriate glycosaminoglycans should be able to bind L-selectin, P-selectin, and/or CD44.
Successful in vitro purging of leukemic blasts from marrow by cortivazol, a pyrazolosteroid: a preclinical study for autologous transplantation in acute lymphoblastic leukemia and non-Hodgkin's lymphoma. (1995)

An important new approach to curative treatment of leukemia is vigorous treatment of autologous marrow to remove residual abnormal cells in vitro prior to reinfusion. This in vitro 'purging' must destroy the malignant cells while preserving sufficient normal precursors to allow re-establishment of normal in vivo function. We have confirmed that cortivazol (CVZ), a glucocorticoid with an unusual structure, can kill dexamethasone (DEX)-resistant leukemic cells and have examined its ability to purge DEX-sensitive (CEM-C7) and -resistant (ICR-27) human leukemic blasts artificially mixed with normal marrow mononuclear cells in vitro. By carefully defining time and dose, we established a 'therapeutic window' that allowed 'cure' of the artificial remission marrow. A sufficient number of viable normal myeloid precursor cells (CFU-GM) remained to suggest that normal marrow precursors adequate for successful marrow transplantation could survive such treatment. CVZ could be a useful drug for in vitro purging of bone marrow for autologous transplantation in patients with acute lymphoblastic leukemia or non-Hodgkin's lymphoma, sensitive or resistant to standard glucocorticoid.
Down-regulation of Myc Is Essential for Terminal Erythroid Maturation (2010)

Terminal differentiation of mammalian erythroid progenitors involves 4-5 cell divisions and induction of many erythroid important genes followed by chromatin and nuclear condensation and enucleation. The protein levels of c-Myc (Myc) are reduced dramatically during late stage erythroid maturation, coinciding with cell cycle arrest in G(1) phase and enucleation, suggesting possible roles for c-Myc in either or both of these processes. Here we demonstrate that ectopic Myc expression affects terminal erythroid maturation in a dose-dependent manner. Expression of Myc at physiological levels did not affect erythroid differentiation or cell cycle shutdown but specifically blocked erythroid nuclear condensation and enucleation. Continued Myc expression prevented deacetylation of several lysine residues in histones H3 and H4 that are normally deacetylated during erythroid maturation. The histone acetyltransferase Gcn5 was up-regulated by Myc, and ectopic Gcn5 expression partially blocked enucleation and inhibited the late stage erythroid nuclear condensation and histone deacetylation. When overexpressed at levels higher than the physiological range, Myc blocked erythroid differentiation, and the cells continued to proliferate in cytokine-free, serum-containing culture medium with an early erythroblast morphology. Gene expression analysis demonstrated the dysregulation of erythropoietin signaling pathway and the up-regulation of several positive regulators of G(1)-S cell cycle checkpoint by supraphysiological levels of Myc. These results reveal an important dose-dependent function of Myc in regulating terminal maturation in mammalian erythroid cells.
Protein Architecture: A Practical Approach (1991)

From the Publisher:
Modern computer graphics transforms protein structures into visually exciting images. 'Protein Architecture: A Practical Approach' shows the reader how to visualize protein structures, and how to design an illustration to help understand and appreciate the variety of protein folding patterns.
Collagen levels in isoproterenol induced myocardial infarction in rats. (1993)

Myocardial infarction was induced in albino rats by the subcutaneous administration of isoproterenol. A significant was observed increase in weight of the myocardium, total protein, DNA levels, neutral salt soluble collagen content, serum and urinary hydroxyproline levels at peak infarction stage in treated rats while the body weight, insoluble and total collagen content of heart were found to be decreased. These results show an early degradation of collagen immediately after myocardial infarction and enhanced synthesis during the different stages of recovery. Histological studies confirmed the incidence of peak infarction after two doses of isoproterenol treatment and recovery to normalcy from the third day onwards.
Congressional samples for approximate answering of group-by queries (2000)

In large data warehousing environments, it is often advantageous to provide fast, approximate answers to complex decision support queries using precomputed summary statistics, such as samples. Decision support queries routinely segment the data into groups and then aggregate the information in each group ( group-by queries). Depending on the data, there can be a wide disparity between the number of data items in each group. As a result, approximate answers based on uniform random samples of the data can result in poor accuracy for groups with very few data items, since such groups will be represented in the sample by very few (often zero) tuples. In this paper, we propose a general class of techniques for obtaining fast, highly-accurate answers for group-by queries. These techniques rely on precomputed non-uniform (biased) samples of the data. In particular, we propose congressional samples , a hybrid union of uniform and biased samples. Given a fixed amount of space, congressional samples seek to maximize the accuracy for all possible group-by queries on a set of columns. We present a one pass algorithm for constructing a congressional sample and use this technique to also incrementally maintain the sample up-to-date without accessing the base relation. We also evaluate query rewriting strategies for providing approximate answers from congressional samples. Finally, we conduct an extensive set of experiments on the TPC-D database, which demonstrates the efficacy of the techniques proposed.
The ARF Tumor Suppressor Inhibits Tumor Cell Colonization Independent of p53 in a Novel Mouse Model of Pancreatic Ductal Adenocarcinoma Metastasis (2011)

Pancreatic ductal adenocarcinoma (PDAC) is an incurable, highly metastatic disease that is largely resistant to existing treatments. A better understanding of the genetic basis of PDAC metastasis should facilitate development of improved therapies. To that end, we developed a novel mouse xenograft model of PDAC metastasis to expedite testing of candidate genes associated with the disease. Human PDAC cell lines BxPC-3, MiaPaCa-2, and Panc-1 stably expressing luciferase were generated and introduced by intracardiac injections into immunodeficient mice to model hematogenous dissemination of cancer cells. Tumor development was monitored by bioluminescence imaging. Bioluminescent MiaPaCa-2 cells most effectively recapitulated PDAC tumor development and metastatic distribution in vivo. Tumors formed in nearly 90% of mice and in multiple tissues, including normal sites of PDAC metastasis. Effects of p14ARF, a known suppressor of PDAC, were tested to validate the model. In vitro, p14ARF acted through a CtBP2-dependent, p53-independent pathway to inhibit MiaPaCa-2-invasive phenotypes, which correlated with reduced tumor cell colonization in vivo. These findings establish a new bioluminescent mouse tumor model for rapidly assessing the biological significance of suspected PDAC metastasis genes. This system may also provide a valuable platform for testing innovative therapies.
Complete Genome Sequence ofRickettsia typhiand Comparison with Sequences of Other Rickettsiae (2004)

Rickettsia typhi, the causative agent of murine typhus, is an obligate intracellular bacterium with a life cycle involving both vertebrate and invertebrate hosts. Here we present the complete genome sequence of R. typhi (1,111,496 bp) and compare it to the two published rickettsial genome sequences: R. prowazekii and R. conorii. We identified 877 genes in R. typhi encoding 3 rRNAs, 33 tRNAs, 3 noncoding RNAs, and 838 proteins, 3 of which are frameshifts. In addition, we discovered more than 40 pseudogenes, including the entire cytochrome c oxidase system. The three rickettsial genomes share 775 genes: 23 are found only in R. prowazekii and R. typhi, 15 are found only in R. conorii and R. typhi, and 24 are unique to R. typhi. Although most of the genes are colinear, there is a 35-kb inversion in gene order, which is close to the replication terminus, in R. typhi, compared to R. prowazekii and R. conorii. In addition, we found a 124-kb R. typhi-specific inversion, starting 19 kb from the origin of replication, compared to R. prowazekii and R. conorii. Inversions in this region are also seen in the unpublished genome sequences of R. sibirica and R. rickettsii, indicating that this region is a hot spot for rearrangements. Genome comparisons also revealed a 12-kb insertion in the R. prowazekii genome, relative to R. typhi and R. conorii, which appears to have occurred after the typhus (R. prowazekii and R. typhi) and spotted fever (R. conorii) groups diverged. The three-way comparison allowed further in silico analysis of the SpoT split genes, leading us to propose that the stringent response system is still functional in these rickettsiae.
Docking Phospholipase A 2 on Membranes Using Electrostatic Potential-Modulated Spin Relaxation Magnetic Resonance (1998)

A method involving electron paramagnetic resonance spectroscopy of a site-selectively spin-labeled peripheral membrane protein in the presence and absence of membranes and of a water-soluble spin relaxant (chromium oxalate) has been developed to determine how bee venom phospholipase A2 sits on the membrane. Theory based on the Poisson-Boltzmann equation shows that the rate of spin relaxation of a protein-bound nitroxide by a membrane-impermeant spin relaxant depends on the distance (up to tens of angstroms) from the spin probe to the membrane. The measurements define the interfacial binding surface of this secreted phospholipase A2.
Effects of Ascorbate on the Oxidation of Derivatives of Hydroxycinnamic Acid and the Mechanism of Oxidation of Sinapic Acid by Cell Wall-Bound Peroxidases (1994)

Journal Article Effects of Ascorbate on the Oxidation of Derivatives of Hydroxycinnamic Acid and the Mechanism of Oxidation of Sinapic Acid by Cell Wall-Bound Peroxidases Get access Umeo Takahama, Umeo Takahama Kyushu Dental CollegeKitakyushu, 803 Japan Search for other works by this author on: Oxford Academic Google Scholar Takayuki Oniki Takayuki Oniki Kyushu Dental CollegeKitakyushu, 803 Japan Search for other works by this author on: Oxford Academic Google Scholar Plant and Cell Physiology, Volume 35, Issue 4, 1994, Pages 593–600, https://doi.org/10.1093/oxfordjournals.pcp.a078634 Published: 01 January 1994 Article history Received: 02 December 1993 Published: 01 January 1994 Accepted: 03 March 1994
Polymer fluctuation lubrication in hydrogel gemini interfaces (2014)

Interfacial sliding speed and contact pressure between the sub-units of particulate soft matter assemblies can vary dramatically across systems and with dynamic conditions. By extension, frictional interactions between particles may play a key role in their assembly, global configuration, collective motion, and bulk material properties. For example, in tightly packed assemblies of microgels - colloidal microspheres made of hydrogel - particle stiffness controls the fragility of the glassy state formed by the particles. The interplay between particle stiffness and shear stress is likely mediated by particle-particle normal forces, highlighting the potential role of hydrogel-hydrogel friction. Here we study friction at a twinned "Gemini" interface between hydrogels. We construct a lubrication curve that spans four orders of magnitude in sliding speed, and find qualitatively different behaviour from traditional lubrication of engineering material surfaces; fundamentally different types of lubrication occur at the hydrogel Gemini interface. We also explore the role played by polymer solubility and hydrogel-hydrogel adhesion in hydrogel friction. We find that polymer network elasticity, mesh size, and single-chain relaxation times can describe friction at the gel-gel interface, including a transition between lubrication regimes with varying sliding speed.
Structural Basis for Nucleotide Binding and Reaction Catalysis in Mevalonate Diphosphate Decarboxylase (2012)

Mevalonate diphosphate decarboxylase (MDD) catalyzes the final step of the mevalonate pathway, the Mg(2+)-ATP dependent decarboxylation of mevalonate 5-diphosphate (MVAPP), producing isopentenyl diphosphate (IPP). Synthesis of IPP, an isoprenoid precursor molecule that is a critical intermediate in peptidoglycan and polyisoprenoid biosynthesis, is essential in Gram-positive bacteria (e.g., Staphylococcus, Streptococcus, and Enterococcus spp.), and thus the enzymes of the mevalonate pathway are ideal antimicrobial targets. MDD belongs to the GHMP superfamily of metabolite kinases that have been extensively studied for the past 50 years, yet the crystallization of GHMP kinase ternary complexes has proven to be difficult. To further our understanding of the catalytic mechanism of GHMP kinases with the purpose of developing broad spectrum antimicrobial agents that target the substrate and nucleotide binding sites, we report the crystal structures of wild-type and mutant (S192A and D283A) ternary complexes of Staphylococcus epidermidis MDD. Comparison of apo, MVAPP-bound, and ternary complex wild-type MDD provides structural information about the mode of substrate binding and the catalytic mechanism. Structural characterization of ternary complexes of catalytically deficient MDD S192A and D283A (k(cat) decreased 10(3)- and 10(5)-fold, respectively) provides insight into MDD function. The carboxylate side chain of invariant Asp(283) functions as a catalytic base and is essential for the proper orientation of the MVAPP C3-hydroxyl group within the active site funnel. Several MDD amino acids within the conserved phosphate binding loop ("P-loop") provide key interactions, stabilizing the nucleotide triphosphoryl moiety. The crystal structures presented here provide a useful foundation for structure-based drug design.
The early blastocyst is bilaterally symmetrical and its axis of symmetry is aligned with the animal-vegetal axis of the zygote in the mouse (1997)

At least one polar body, almost invariably the second, persists intact to the early blastocyst stage in nearly two-thirds of mouse conceptuses of the PO strain. The distribution in early blastocysts of these surviving polar bodies was highly non-random. Most not only lay in the mid-region of the embryonic-abembryonic axis but, on discovering that early blastocysts are bilaterally rather than radially symmetrical about this axis, were found to align with the bilateral axis. Cell marking experiments failed to detect movement of polar bodies relative to the surface of the conceptus during either cleavage or blastulation. That the distribution of degenerating polar bodies and their presumed debris was similar to intact ones also argued against their motility, as did the finding that at all stages second polar bodies were attached to conceptuses by a thin, extensible, weakly elastic 'tether'. Although the transfer of small fluorochromes between them was rarely observed beyond second cleavage, the second polar body and conceptus could remain coupled ionically up to the blastocyst stage. It is concluded that the second polar body normally remains attached to the conceptus through persistence of the intercellular bridge formed during its abstriction, and therefore provides an enduring marker of the animal pole of the zygote. Hence, according to the distribution of polar bodies, the axis of bilateral symmetry of the early blastocysts is normally aligned with the animal-vegetal axis of the zygote and its embryonic-abembryonic axis is orthogonal to it. Such relationships suggest that, at least in undisturbed development, specification of the axes of the blastocyst depends on spatial patterning of the zygote.
Microscale Control of Cell Contact and Spacing via Three-Component Surface Patterning (2007)

The complexity of micropatterned cell constructs has been limited by difficulties in patterning more than two surface components on a culture substrate. Photolithography using multiple aligned masks is well established for generalized multicomponent patterning, but is often too harsh for biomolecules. We report a two-mask photolithographic process that is tuned to preserve bioactivity in patterns composed of covalently coupled poly(ethylene glycol) (PEG), adsorbed extracellular matrix protein (e.g., collagen I), and adsorbed serum proteins (e.g., vitronectin). Thereby, we pattern two cell types-primary hepatocytes and 3T3 fibroblasts-demonstrating control over contact and spacing (20-200 microm) between the two cell types for over one week. This method is applicable to the study of intercellular communication in cell biology and tissue engineering.
Proteins binding to 5' untranslated region sites: a general mechanism for translational regulation of mRNAs in human and yeast cells. (1994)

We demonstrate that a bacteriophage protein and a spliceosomal protein can be converted into eukaryotic translational repressor proteins. mRNAs with binding sites for the bacteriophage MS2 coat protein or the spliceosomal human U1A protein were expressed in human HeLa cells and yeast. The presence of the appropriate binding protein resulted in specific, dose-dependent translational repression when the binding sites were located in the 5' untranslated region (UTR) of the reporter mRNAs. Neither mRNA export from the nucleus to the cytoplasm nor mRNA stability was demonstrably affected by the binding proteins. The data thus reveal a general mechanism for translational regulation: formation of mRNA-protein complexes in the 5' UTR controls translation initiation by steric blockage of a sensitive step in the initiation pathway. Moreover, the findings establish the basis for novel strategies to study RNA-protein interactions in vivo and to clone RNA-binding proteins.
Molecular responses of human dermal fibroblasts to dual cues: Contact guidance and mechanical load (2000)

Fibroblast contraction in wound healing involves the interaction of several cell types, cytokines, and extracellular matrix molecules. We have previously developed fibroblast alignment models using precise uniaxial mechanical loads in 3D culture and using contact guidance on fibronectin strands. Our aim here was to use contact guidance to place fibroblasts in their potentially most sensitive configuration, i.e., perpendicular to the axis of loading, to present cells with conflicting guidance cues. Gene expression at the mRNA level of cells recovered from different zones of the 3D collagen gel (with distinct orientation) was determined by quantitative RT-PCR for the matrix proteases MMP1, 2, and 3, and inhibitors TIMP1 and 2. Our results show a 2-, 4-, and 3-fold increase in MMP1, 2, and 3, respectively, in the non-aligned strain zone, relative to the aligned strain zone. These results suggest that cells unable to align to applied loads remodel their matrix far more rapidly than orientated cells. Where fibroblasts were held in an alignment perpendicular to the applied load by contact guidance, the fall in MMP mRNA expression was largely abolished, indicating that these cells remained in a mechano-activated state. The protease inhibitors TIMP1 and 2 were poorly mechano-responsive, further suggesting that changes in MMP expression result in functional matrix remodelling. These results indicate how mechanical loading in tissues may influence matrix remodelling, particularly under conflicting guidance cues.
Compact cylindrical sector dielectric resonator antennas (2002)

We investigate cylindrical sector dielectric resonator antenna (DRA) geometries that are formed by removing a sector (or equivalently a wedge) of dielectric material from a circular cylinder. The advantage this geometry offers, compared to conventional cylindrical DRAs, are reductions in volume, support of "fractional modes", and allowance of dual-frequency/dual-feed operation. Approximate theory, simulation and experimental results are provided to support our findings. In particular, a cylindrical sector DRA is demonstrated to have 75% less volume than a conventional cylindrical DRA, with the same resonant frequency, giving it potential for use in wireless communication handsets.
Synchronization of Plasmodium falciparum gametocytes using an automated suspension culture system (1986)

An automated suspension culture system for the cultivation of Plasmodium falciparum is described which retains a degree of flexibility which is absent in other automated culture apparatuses. Not only does this system of cultivation promote rapid multiplication of asexual parasites but also permits the development and maturation of gametocytes. Using a combination of gelatin flotation and N-acetyl glucosamine treatment synchronous development of gametocytes was achieved. The total time for gametocyte maturation in vitro under the conditions provided was 7 days. Stages II and V required 48 h for development whilst I, III and IV needed 24 h each. Mature microgametocytes were relatively long lived in comparison with macrogametocytes. Electron microscopic study of the synchronized stages confirmed the observations of Sinden (1982) but, in addition, we noted the presence of Garnham bodies, a cytostome in all stages and dense spherules in stages I-III similar to the fenestrated buttons in sporozoites and exoerythrocytic forms. The relationship between the number of osmiophilic bodies in the mature gametocytes and their ability to escape from the red cell is reaffirmed.
A generic framework for modeling resources with UML (2000)

Current wisdom encourages designers to first focus on the logical aspects of their problem and then defer platform and technology issues until the concluding phases of development. This behavior is reasonable, considering that devising logically sound solutions is frequently the most difficult aspect of development. Unfortunately-and this has been understated to date-there are many situations in which this approach is inappropriate. Real-time software design is one domain where this situation is particularly obvious because the domain's requirements force software to interact with the physical world in some way. Recently, a generic object oriented framework has been proposed for modeling both physical and logical resources. Although the framework is generic, it is mainly used with the industry-standard Unified Modeling Language (UML). By providing a standard means for representing resources and their attributes, it becomes possible to seamlessly transfer UML models of real-time systems between design and specialized analysis tools. The author shows how developers can use the OMG's UML to model resources and thus predict crucial system properties before fully implementing a system.