gebhart/patrepeval huggingface dataset:
Thermodynamics of Bovine Spleen Galectin-1 Binding to Disaccharides: Correlation with Structure and Its Effect on Oligomerization at the Denaturation Temperature (1998)

Isothermal titration calorimetry (ITC) measurements of the binding 1-beta carbohydrate-substituted galactopyranoside derivatives to galectin-1 from bovine spleen, a dimer with one binding site per subunit, were performed at 283-285 and 298 K. The disaccharides were lactose, methyl beta-lactoside, lactulose, 4-O-beta-D-galactopyranosyl-D-mannopyranoside, 3-O-beta-D-galactopyranosyl-D-arabinose, 2'-O-methyllactose, lacto-N-biose, N-acetyllactosamine, and thiodigalactopyranoside. The site binding enthalpies, DeltaHb, are the same at both temperatures and range from -42.2 +/- 3.3 kJ mol-1 for thiodigalactopyranoside to -24.5 +/- 0.5 kJ mol-1 for lacto-N-biose, and the site binding constants range from 4.86 +/- 0.78 x 10(3) M-1 for methyl beta-lactoside at 297.8 K to 6.54 +/- 0.97 x 10(4) M-1 for N-acetyllactosamine at 281.3 K. The binding reactions are enthalpically driven, exhibit enthalpy-entropy compensation, and, with the exception of N-acetyllactosamine, follow a van't Hoff dependence of the binding constant on temperature. The number of contacts at distances <4.0 A between the disaccharide and galectin was determined from the energy-minimized conformation of the complex derived from the X-ray crystallographic structure of the galectin-N-acetyllactosamine complex determined by Liao et al. [Liao, D. I., Kapadia, G., Ahmed, H., Vasta, G. R., and Herzberg, O. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 1428-1432]. The binding enthalpies calculated from changes in the solvent-accessible surface areas of the galectin binding site upon binding of the disaccharide were in close agreement with the experimental values for lactose, lactulose, lacto-N-biose, and N-acetyllactosamine, all of which exhibit binding enthalpies >-36 kJ mol-1. Differential scanning calorimetry measurements on solutions of galectin and its disaccharide complexes show that the galectin dimer does not dissociate upon denaturation in contrast to the legume lectins. At the denaturation temperature, the galectin in the absence of sugar exists as a tetramer, and the extent of this association is substantially reduced in the presence of a disaccharide.
Platelet‐Derived Growth Factor Enhancement of Two Alloplastic Bone Matrices (2005)

These experiments demonstrate the feasibility of using PDGF-BB in combination with alloplastic materials such as beta-TCP or CaSO(4) to serve as more effective bone graft materials with enhanced osteogenic properties.
Probability and Measure. (1996)

Probability. Measure. Integration. Random Variables and Expected Values. Convergence of Distributions. Derivatives and Conditional Probability. Stochastic Processes. Appendix. Notes on the Problems. Bibliography. List of Symbols. Index.
IN architectures for implementing universal personal telecommunications (1994)

This article focuses on architectures for providing universal personal telecommunications (UPT) service to wireline users. Although UPT services could be provided to users of wireless phones, thereby giving those users personal communication services (PCS), the wireline environment introduces certain important complications. Unlike "smart" cellular phones, which can register themselves and the user automatically, wireline telephones are unable to automatically detect and register a UPT user. UPT therefore includes a manual registration procedure to associate a PTN with the phone where calls will be received or placed. Also, unlike personal communications terminals that are typically used by only one person, wireline phones are likely to be shared among other users. Therefore, the network must keep track of who is using the phone, so it can provide the appropriate telecommunications services. It would be difficult or impossible to implement UPT as a switch-based service. Fortunately, an intelligent network (IN) architecture that is well suited for implementing UPT is being deployed by many local exchange (LECs) and interexchange carriers (IXCs).< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Peptide quantitative structure-activity relationships, a multivariate approach (1987)

The variation in amino acid sequence within sets of peptides is described by three principal properties, z1, z2, and z3, per varied amino acid position. These principal properties are derived from a principal components analysis of a matrix of 29 physicochemical variables for the 20 coded (in mRNA) amino acids. The scales z1, z2, and z3 are used to construct informative sets of analogues for exploring and developing quantitative structure-activity relationships (QSAR) of peptides. For the QSARs, the multivariate partial least squares (PLS) method is used. Multivariate QSARs are developed for four families of peptides, and it is shown how these QSARs can predict the activity of new peptide analogues.
Trimeric Assembly and Three-Dimensional Structure Model of the FACIT Collagen COL1−NC1 Junction from CD and NMR Analysis (1996)

The 3D structure of the COL1-NC1 junction of FACIT type XIV collagen was investigated using GYCDPSSCAG and (GPP*)3GYCDPSSCAG synthetic peptides, circular dichroism, and NMR. At -20 degrees C and under air oxidation catalyzed by Cu2+, the peptide (GPP*)3GYCDPSSCAG is able to self-associated with high yield into a stable triple disulfide bonded trimer. The presence of a triple helical conformation was confirmed by circular dichroism. The analysis of the trimer by 2D NMR provided a set of distance constraints for the noncollagenous part. Molecular models for the 3D structure of COL1-NC1 junction were calculated, using the NMR distance constraints in combination with the 3D structural data recently established by X-ray crystallography [Bella, J., Eaton, M., Brodsky, B., & Berman, H. M. (1994) Science 266, 75-81] for a collagenous triple helix. From the eight theoretically possible arrangements for the three interchain disulfide bonds, only two close disulfide conformers are compatible with the experimental data. The main feature of the trimer structure is the asymmetry of the molecule due to the disulfide bond pattern that induces a particular folding of one chain. This chain forms a turn-like structure locked by two disulfide bonds with the two other chains. The turn-like folding is close to that observed for the cyclized oxidized monomeric peptide. This is the first report of the 3D structure model for a junction between a collagenous triple helical domain and a noncollagenous domain.
Improvements to Burrows-Wheeler compression algorithm (2000)

In 1994 Burrows and Wheeler presented a new algorithm for lossless data compression. The compression ratio that can be achieved using their algorithm is comparable with the best known other algorithms, whilst its complexity is relatively small. In this paper we explain the internals of this algorithm and discuss its various modifications that have been presented so far. Then we propose new improvements for its effectiveness. They allow us to obtain a compression ratio equal to 2.271 bpc for the Calgary Corpus files, which is the best result in the class of Burrows–Wheeler transform based algorithms. Copyright © 2000 John Wiley & Sons, Ltd.
Thermodynamic analysis of phase stability of nanocrystalline titania (1998)

The phase stability of nanocrystalline anatase and rutile was analyzed thermodynamically. According to the present analysis, anatase becomes more stable than rutile when the particle size decreases belowca. 14 nm. The calculated phase boundary between nanocrystalline anatase and rutile coincides with the experimental data for appearance of rutile during coarsening of nanocrystalline anatase. Both surface free energy and surface stress play important roles in the thermodynamic phase stability, which is a function of particle size.
Dogs Infected with a Human Granulocytotropic Ehrlichia spp. (Rickettsiales: Ehrlichieae) (1997)

Dogs were found to be susceptible to human granulocytotropic Ehrlichia spp. Infection was produced through the bite of Ixodes scapularis Say (= dammini Spielman, Clifford, Piesman & Corwin) nymphs and adults that acquired infection while feeding as larvae on experimentally infected mice. Dogs were also infected by intravenous injection of mouse blood or dog blood from parasitemic donors. Parasites were demonstrable in neutrophils within 8 or 9 d after nymphs began feeding; prepatent periods were longer when infection was induced by adult tick feeding (18 d) or by transfusion of mouse blood (12 d). The shortest prepatent period observed was 5 d in a dog infected by transfusion of blood from a parasitemic dog. Infections in dogs were mild and apparently transient. Mild thrombocytopenia was the most commonly observed abnormality. Parasites could be detected by light microscopy during the acute phase of infection (4 or 5 d) and parasite DNA by polymerase chain reaction as early as 5 d after exposure but not at 6-9 d after morulae were first observed in neutrophils. Likewise, dog blood was infectious for mice at 2 d but not at 25 d, and for dogs at 3 d but not at 13 d after morulae were first observed in neutrophils. Seroconversion occurred as early as 11 d after onset of tick feeding and persisted until dogs were euthanatized. Gross and histopathologic lesions were similar to those observed in dogs with E. canis (Donatien & Lestoquard), E. chaffeensis Anderson, Dawson & Wilson, and E. ewingii Anderson, Greene, Jones & Dawson infections but were generally milder than any of these. The moderate enlargement of lymphoid organs observed grossly was reflected histologically as mild to moderate reactive hyperplasia, which was largely follicular (B cell).
Ephrin-A1 binding to CD4+ T lymphocytes stimulates migration and induces tyrosine phosphorylation of PYK2 (2004)

Eph receptors, the largest subfamily of receptor tyrosine kinases, and their ephrin ligands are important mediators of cell-cell communication regulating cell attachment, shape, and mobility. Here we demonstrate that CD4+ T lymphocytes express the EphA1 and EphA4 receptors and that these cells bind the ligand ephrin-A1. Further we show ephrin-A1 expression in vivo on high endothelial venule (HEV) endothelial cells. Ephrin-A1 binding to CD4+ T cells stimulates both stromal cell-derived factor 1alpha (SDF-1alpha)- and macrophage inflammatory protein 3beta (MIP3beta)-mediated chemotaxis. In line with the increased chemotactic response, increased actin polymerization is observed in particular with the combination of ephrin-A1 and SDF-1alpha. Signaling through EphA receptors induces intracellular tyrosine phosphorylation. In particular, proline-rich tyrosine kinase 2 (PYK2) is phosphorylated on tyrosine residues 402 and 580. Ephrin-A1-induced chemotaxis and intracellular tyrosine phosphorylation, including EphA1 and Pyk2, was inhibited by Tyrphostin-A9. In conclusion, ligand engagement of EphA receptors on CD4+ T cells stimulates chemotaxis, induces intracellular tyrosine phosphorylation, and affects actin polymerization. This, together with our finding that ephrin-A1 is expressed by HEV endothelial cells, suggests a role for Eph receptors in transendothelial migration.
WDM protocol-transparent distance extension using R2 remodulation (1996)

In computer networks using wavelength-division multiplexing (WDM), it is often necessary to extend the length of a given WDM path beyond that of a single segment whose length Is limited by the link budget. While wavelength-flattened optical amplifiers are the most obvious solution, this paper calls attention to a simple (albeit less efficient) alternative that works for any number of wavelength channels, but only a modest number of segments and modest bit rates. This scheme substitutes for each optical amplifier stage a multiwavelength 2R remodulator consisting of a WDM demultiplexor, followed by wavelength-by-wavelength zero-crossing detectors, then remodulation wavelength by wavelength, and finally wavelength-division multiplexing back onto a single fiber. Theory and experimental results confirm the usefulness of this primitive technique, which can also be used for add-and-drop links, for wavelength routing or wavelength conversion in scalable wavelength routing networks, for internetwork gateways, and for other applications.
Type III Secretion Systems and Disease (2007)

Type III secretion systems (T3SSs) are complex bacterial structures that provide gram-negative pathogens with a unique virulence mechanism enabling them to inject bacterial effector proteins directly into the host cell cytoplasm, bypassing the extracellular milieu. Although the effector proteins vary among different T3SS pathogens, common pathogenic mechanisms emerge, including interference with the host cell cytoskeleton to promote attachment and invasion, interference with cellular trafficking processes, cytotoxicity and barrier dysfunction, and immune system subversion. The activity of the T3SSs correlates closely with infection progression and outcome, both in animal models and in human infection. Therefore, to facilitate patient care and improve outcomes, it is important to understand the T3SS-mediated virulence processes and to target T3SSs in therapeutic and prophylactic development efforts.
The Outer Membrane of Treponema pallidum: Biological Significance and Biochemical Properties (1985)

Rabbits infected intravenously with Treponema pallidum were not markedly febrile, and the pyrogenicity of treponeme preparations administered intravenously to rabbits was negligible. The antibiotic polymyxin B did not induce any ultrastructural changes on the treponemal surface and was not lethal (immobilizing) for T. pallidum, which was, however, highly susceptible to detergents such as SDS. Extraction of treponemes with Triton X-100 removed the outer membrane (despite the presence of Mg2+) as shown by electron microscopy, and solubilized a limited number of proteins detectable by SDS-PAGE, including a dominant antigen (47 kDal) demonstrated by immunoblotting. None of the proteins were heat-modifiable. Periodic acid-silver staining of polyacrylamide gels for carbohydrate together with protease K digestion did not demonstrate major carbohydrate components in whole treponemes, or in the Triton-soluble fraction. Surface iodination of intact treponemes revealed very little surface exposure of treponemal proteins, although a protein which co-migrated with host albumin was labelled and appeared to be associated with the treponemal surface. Many treponemal proteins were, however, labelled when iodination was done in the presence of Triton. These observations, indicate that the outer membrane of T. pallidum differs significantly from those of many Gram-negative pathogens.
Low Dose Geldanamycin Inhibits Hepatocyte Growth Factor- and Hypoxia-Stimulated Invasion of Cancer Cells (2007)

AbstractHepatocyte growth factor (HGF) receptor Met and hypoxia-inducible factor-1 (HIF-1) signaling pathways are commonly activated in aggressive tumors and promote progression. Since both Met and HIF-1α proteins are heat shock protein (Hsp) 90 clients, Hsp90 inhibitors might be expected to positively impact tumor progression. Here, we systematically evaluated the inhibitory effects of the prototypical Hsp90 inhibitor geldanamycin (GA) on cellular processes involved in invasion and angiogenesis in T24 bladder cancer cells stimulated with HGF and chemical hypoxia. First, we demonstrated the positive feedback loop between Met and HIF-1 pathways, which serves to sustain and amplifies their signaling in T24 cells. GA down-regulated Met by inhibiting new protein maturation, thereby dampening HGF signaling. HGF and chemical hypoxia with CoCl2 cooperatively promoted in vitro invasion and vascular endothelial growth factor (VEGF) secretion, while CoCl2 but not HGF activated urokinase-type plasminogen activator and matrix metalloproteinase 2, both of which promote invasion and angiogenesis. Low dose GA (100 nmol/L) inhibited these processes by suppressing both HGF and HIF-1 pathways. Notably, brief GA pretreatment inhibited in vitro invasion and VEGF secretion induced by HGF as effectively as did continuous treatment. Moreover, we found that GA inhibited activation of focal adhesion kinase, focal adhesion assembly, and actin reorganization induced by HGF and integrin engagement by extracellular matrix. Thus, GA widely suppresses extrinsic stimuli-induced signaling that contribute to tumor invasion and angiogenesis in this bladder carcinoma model, suggesting the utility of Hsp90 inhibitors in preventing tumor progression and metastasis.
Improved tumor imaging and therapy via i.v. IgG–mediated time-sequential modulation of neonatal Fc receptor (2007)

The long plasma half-life of IgG, while allowing for enhanced tumor uptake of tumor-targeted IgG conjugates, also results in increased background activity and normal-tissue toxicity. Therefore, successful therapeutic uses of conjugated antibodies have been limited to the highly sensitive and readily accessible hematopoietic tumors. We report a therapeutic strategy to beneficially alter the pharmacokinetics of IgG antibodies via pharmacological inhibition of the neonatal Fc receptor (FcRn) using high-dose IgG therapy. IgG-treated mice displayed enhanced blood and whole-body clearance of radioactivity, resulting in better tumor-to-blood image contrast and protection of normal tissue from radiation. Tumor uptake and the resultant therapeutic response was unaltered. Furthermore, we demonstrated the use of this approach for imaging of tumors in humans and discuss its potential applications in cancer imaging and therapy. The ability to reduce the serum persistence of conjugated IgG antibodies after their infusion can enhance their therapeutic index, resulting in improved therapeutic and diagnostic efficacy.
Antagonist of monocyte chemoattractant protein 1 ameliorates the initiation and progression of lupus nephritis and renal vasculitis in MRL/lpr mice (2003)

We established a new system using MRL/N-1 cells that allows long-term observation of the effects of chemokine antagonists on lupus nephritis in MRL/lpr mice. We also showed that the MCP-1 antagonist ameliorated the initiation and progression of lupus nephritis and of renal vasculitis, which might provide a new approach to the treatment of the disease.
Prediction of the potency of inhibitors of adenosine deaminase by QM/MM calculations (2003)

QM/MM calculations show that the potency of a range of inhibitors of adenosine deaminase correlates with the relative stability of the reaction intermediate at the active site, rather than with the inhibitor binding energy.
H(+)-ATPase gamma subunit of Escherichia coli. Role of the conserved carboxyl-terminal region. (1990)

Cloned uncG genes (wild-type or in vitro mutagenized) for the Escherichia coli gamma subunit were introduced into the uncG mutant Gln-14----end), and the functions of the mutant subunits were studied. The F1's with Ala-283----end and Thr-277----end mutant gamma subunits had 63 and 14% of the wild-type ATPase activity, respectively, and mutants with these subunits showed reduced growth by oxidative phosphorylation, indicating that the 10 residues at the carboxyl terminus (286th residue) are important, but dispensable, for catalysis. On the other hand, F1 with a Gln-269----end gamma subunit was inactive. Replacement of conserved residues (Gln-269, Thr-273, or Glu-275) between Gln-269 and Leu-276 gave enzymes with significantly reduced ATPase activity (2-41% of that of the wild-type) and lower ATP-driven proton conduction. Thus these residues are required for the normal catalytic activity of F1, although they are not absolutely essential. Membranes with amino acid replacements (Thr-277----end, Gln-269----Leu, or Glu-275----Lys) and the frameshift mutation (downstream of Thr-277) had about 15% of the wild-type ATPase activity, but showed different degrees of ATP-dependent H+ translocation and growth yield by oxidative phosphorylation, suggesting that the gamma subunit, especially its carboxyl-terminal region, functions in coupling between catalysis and H+ translocation.
Motility and chemotaxis of three strains of Pseudomonas aeruginosa used for virulence studies (1981)

The motility and chemotaxis of three strains of Pseudomonas aeruginosa were examined by electron microscopy, soft agar migration, and the capillary assay test. Strain M2, which is highly virulent in the burned mouse model, was vigorously motile and highly chemotactic. The avirulent strains tested, PA103 and WR5, were defective in motility and chemotaxis, respectively. These results suggest that considerable heterogeneity in chemotactic capacity exists among the P. aeruginosa strains that are used for virulence studies, and further, that chemotaxis should be examined as a possible virulence factor for P. aeruginosa.
Domain name system implementation schedule (1984)

This memo is a policy statement on the implementation of the Domain
Style Naming System in the Internet. This memo is a partial update of
RFC 881. The intent of this memo is to detail the schedule for the
implementation for the Domain Style Naming System. The names of hosts
will be changed to domain style names. Hosts will begin to use domain
style names on 14-Mar-84, and the use of old style names will be
completely phased out before 2-May-84. This applies to both the ARPA
research hosts and the DDN operational hosts. This is an official
policy statement of the ICCB and the DARPA.
A Long-Acting, Highly Potent Interferon α-2 Conjugate Created Using Site-Specific PEGylation (2005)

Recombinant interferon α-2 (IFN-α2) is used clinically to treat a variety of viral diseases and cancers. IFN-α2 has a short circulating half-life, which necessitates frequent administration to patients. Previous studies showed that it is possible to extend the circulating half-life of IFN-α2 by modifying lysine residues of the protein with amine-reactive poly(ethylene glycol) (PEG) reagents. However, amine-PEGylated IFN-α2 comprises a heterogeneous product mixture with low specific activity due to the large number and critical locations of lysine residues in IFN-α2. In an effort to overcome these problems we determined the feasibility of creating site-specific, mono-PEGylated IFN-α2 analogues by introducing a free (unpaired) cysteine residue into the protein, followed by modification of the added cysteine residue with a maleimide-PEG reagent. IFN-α2 cysteine analogues were expressed in Escherichia coli and purified, and their in vitro bioactivities were measured in the human Daudi cell line growth inhibition assay. Several cysteine analogues were identified that do not significantly affect in vitro biological activity of IFN-α2. Certain of the cysteine analogues, but not wild-type IFN-α2, reacted with maleimide-PEG to produce mono-PEGylated proteins. The PEG−Q5C analogue retained high in vitro bioactivity (within 3- to 4-fold of wild-type IFN-α2) even when modified with 20- and 40-kDa PEGs. Pharmacokinetic experiments indicated that the 20-kDa PEG−Q5C and 40-kDa PEG−Q5C proteins have 20-fold and 40-fold longer half-lives, respectively, than IFN-α2 following subcutaneous administration to rats. These studies demonstrate the feasibility of using site-specific PEGylation technology to create a long-acting, mono-PEGylated IFN-α2 protein with high specific activity.