gebhart/patrepeval huggingface dataset:
Biodegradable and Biocompatible Synthetic Saccharide−Peptide Hydrogels for Three-Dimensional Stem Cell Culture (2011)

Saccharide-peptide hydrogels have been developed in our laboratory as new synthetic extracellular matrices for regenerative medicine applications. In this work, we have expanded on our previously reported system and applied copolymerization of cysteine (Cys) and vinyl sulfone (VS)-functionalized saccharide-peptide polymers via Michael-type addition for encapsulation and 3D culture of cells. Specifically, our aims were to (1) develop a novel hydrogel platform, which could be applied for encapsulating and culturing mesenchymal stem cells (MSCs) in a 3D environment, (2) characterize the tunable properties of the hydrogel, specifically, degradation, mechanical, and gel network properties, and (3) determine the biocompatibility of the saccharide-peptide hydrogel material with MSCs. Hydrogel mechanical properties were tunable by varying the VS:Cys ratio (= 0.5, 1, or 2) as well as the pH (6, 7, or 8) of the cross-linking components. Stiffer gels were formed at VS:Cys = 1 and pH 6 or 7. Gels formed at pH 8 or with excess Cys (VS:Cys = 0.5) or VS (VS:Cys = 2) were significantly softer. Cross-linking pH and VS:Cys ratio also had an effect on the degradation behavior of the VS:Cys gels, with higher cross-linking pH resulting in an accelerated loss of mass. On the basis of environmental scanning electron microscopy (ESEM) analysis and fluorescence microscopy, all hydrogels appeared to exhibit porous gel networks. MSCs cultured in monolayer and exposed to soluble Cys or VS copolymers (0.1-5 mg/mL) did not exhibit measurable cytotoxicity. In addition, MSCs were cultured in 3D for up to 14 days in vitro without deleterious effects on cell viability. In summary, we have established and characterized a tunable 3D saccharide-peptide hybrid copolymer hydrogel platform for culturing MSCs. Future studies will focus on utilizing the hydrogel system for controlling the differentiation of MSCs.
Human immunodeficiency virus Tat transactivation: induction of a tissue-specific enhancer in a nonpermissive cell line (1991)

The enhancer of the human neurotropic papovavirus JC virus (JCV) restricts viral transcription to glial cells. We utilized the tissue specificity of the JCV enhancer as a tool to investigate the function of human immunodeficiency virus (HIV) Tat in transcriptional activation. The reporter plasmid pJCTAR-CAT was constructed by inserting the HIV type 1 Tat-responsive element, TAR, between the JCV promoter and the chloramphenicol acetyltransferase (CAT) gene. Cotransfection of pJCTAR-CAT and pSV-Tat, an expression vector for Tat, resulted in a 50-fold increase in JCV promoter activity in cells nonpermissive for JCV expression. Both the 98-bp JCV enhancer and the HIV TAR sequences were required for transactivation of pJCTAR-CAT in nonpermissive cells. The transactivation by Tat occurred at the level of transcription, as the increase in CAT activity paralleled an increase in the steady-state levels of CAT mRNA in S1 nuclease and nuclear run-on analyses. In the presence of Tat, the JCV enhancer is functional in cells normally nonpermissive for JCV expression; therefore, our results provide unique evidence that HIV type 1 Tat may regulate the activity of specific transcription factors.
Dynamic Regulation of Cystic Fibrosis Transmembrane Conductance Regulator by Competitive Interactions of Molecular Adaptors (2007)

Disorganized ion transport caused by hypo- or hyperfunctioning of the cystic fibrosis transmembrane conductance regulator (CFTR) can be detrimental and may result in life-threatening diseases such as cystic fibrosis or secretory diarrhea. Thus, CFTR is controlled by elaborate positive and negative regulations for an efficient homeostasis. It has been shown that expression and activity of CFTR can be regulated either positively or negatively by PDZ (PSD-95/discs large/ZO-1) domain-based adaptors. Although a positive regulation by PDZ domain-based adaptors such as EBP50/NHERF1 is established, the mechanisms for negative regulation of the CFTR by Shank2, as well as the effects of multiple adaptor interactions, are not known. Here we demonstrate a physical and physiological competition between EBP50-CFTR and Shank2-CFTR associations and the dynamic regulation of CFTR activity by these positive and negative interactions using the surface plasmon resonance assays and consecutive patch clamp experiments. Furthermore whereas EBP50 recruits a cAMP-dependent protein kinase (PKA) complex to CFTR, Shank2 was found to be physically and functionally associated with the cyclic nucleotide phosphodiesterase PDE4D that precludes cAMP/PKA signals in epithelial cells and mouse brains. These findings strongly suggest that balanced interactions between the membrane transporter and multiple PDZ-based adaptors play a critical role in the homeostatic regulation of epithelial transport and possibly the membrane transport in other tissues.
Positive selection on the H3 hemagglutinin gene of human influenza virus A (1999)

The hemagglutinin (HA) gene of influenza viruses encodes the major surface antigen against which neutralizing antibodies are produced during infection or vaccination. We examined temporal variation in the HA1 domain of HA genes of human influenza A (H3N2) viruses in order to identify positively selected codons. Positive selection is defined for our purposes as a significant excess of nonsilent over silent nucleotide substitutions. If past mutations at positively selected codons conferred a selective advantage on the virus, then additional changes at these positions may predict which emerging strains will predominate and cause epidemics. We previously reported that a 38% excess of mutations occurred on the tip or terminal branches of the phylogenetic tree of 254 HA genes of influenza A (H3N2) viruses. Possible explanations for this excess include processes other than viral evolution during replication in human hosts. Of particular concern are mutations that occur during adaptation of viruses for growth in embryonated chicken eggs in the laboratory. Because the present study includes 357 HA sequences (a 40% increase), we were able to separately analyze those mutations assigned to internal branches. This allowed us to determine whether mutations on terminal and internal branches exhibit different patterns of selection at the level of individual codons. Additional improvements over our previous analysis include correction for a skew in the distribution of amino acid replacements across codons and analysis of a population of phylogenetic trees rather than a single tree. The latter improvement allowed us to ascertain whether minor variation in tree structure had a significant effect on our estimate of the codons under positive selection. This method also estimates that 75.6% of the nonsilent mutations are deleterious and have been removed by selection prior to sampling. Using the larger data set and the modified methods, we confirmed a large (40%) excess of changes on the terminal branches. We also found an excess of changes on branches leading to egg-grown isolates. Furthermore, 9 of the 18 amino acid codons, identified as being under positive selection to change when we used only mutations assigned to internal branches, were not under positive selection on the terminal branches. Thus, although there is overlap between the selected codons on terminal and internal branches, the codons under positive selection on the terminal branches differ from those on the internal branches. We also observed that there is an excess of positively selected codons associated with the receptor-binding site and with the antibody-combining sites. This association may explain why the positively selected codons are restricted in their distribution along the sequence. Our results suggest that future studies of positive selection should focus on changes assigned to the internal branches, as certain of these changes may have predictive value for identifying future successful epidemic variants.
Structure and relaxation properties of medical‐purposed polyacrylamide gels (2005)

Abstract By IR and NMR spectroscopy methods, thermomechanical analysis, mechanical relaxation measurements, and computational simulation the effect of production conditions of acrylamide copolymer and N , N ′‐methylenebisacrylamide derived hydrogels with respect to their properties were studied. Four hydrogel samples, prepared under different production conditions (γ‐radiation dose and autoclaving), were investigated. It was found that autoclaving and γ‐radiation lead to a slight increase of the crosslinking degree in the polymeric network and formation of alkene structures in polymeric chains. Stress relaxation and creep processes under axial compression of gel cylindrical samples were studied in detail. To approximate stress relaxation and creep curves new memory functions were used, based on the analysis of entropy production in the system during the relaxation process. It was found that primary γ‐radiation of initial gels induces an increase of quasi‐equilibrium rubbery elasticity modulus, and quasi‐equilibrium compliance is decreased. The opposite situation is observed during further autoclaving at 120°C. After autoclaving, required to sterilize the gels, their treatment by γ‐radiation again induced a noticeable increase of the modulus and compliance decrease. The mechanism of relaxation processes was found to be associated with the limiting stage of physical interaction between relaxants, representing different micro‐inhomogeneities in the material. The investigation results were compared with the data obtained by histology and morphology methods. A hydrogel obtained under additional γ‐radiation treatment and autoclaving did not swell when implanted into a living organism, and the tissue reaction to implantation of such gel was minimal. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1043–1058, 2005
Similar postprandial glycemic reductions with escalation of dose and administration time of American ginseng in type 2 diabetes. (2000)

AG reduced PPG irrespective of dose and time of administration. No more than 3 g AG was required at any time in relation to the challenge to achieve reductions. Because these reductions included glycemia at the 2-h diagnostic end point, there may be implications for diabetes diagnosis and treatment.
An Evaluation of the Long-Term Stagnancy of Porewater in the Neogene Sedimentary Rocks in Northern Japan (2018)

A groundwater dating for very old porewater using 36 Cl and 4 He was applied to the Koetoi and Wakkanai formations distributed in the northernmost part in Japan. Measured 36 Cl/Cl in the Koetoi Formation was 2.6 ± 2.0 × 10 −15 and that in the Wakkanai Formation was 8.1 ± 2.5 × 10 −15 . These values are similar to 36 Cl/Cl in situ secular equilibrium calculated from chemical compositions of core suggesting that Cl − ions and porewater have remained in the formations for much longer than half-life of 36 Cl . He concentration in porewater ranged from 1.1 × 10 −6 to 2.6 × 10 −5 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:msub><mml:mrow><mml:mi mathvariant="normal">c</mml:mi><mml:mi mathvariant="normal">c</mml:mi></mml:mrow><mml:mrow><mml:mi mathvariant="normal">S</mml:mi><mml:mi mathvariant="normal">T</mml:mi><mml:mi mathvariant="normal">P</mml:mi></mml:mrow></mml:msub><mml:mo> </mml:mo><mml:msup><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant="normal">g</mml:mi></mml:mrow><mml:mrow><mml:mi mathvariant="normal">w</mml:mi></mml:mrow></mml:msub></mml:mrow><mml:mrow><mml:mo>-</mml:mo><mml:mn mathvariant="normal">1</mml:mn></mml:mrow></mml:msup></mml:math>) and it is much higher than water saturated with air indicating that both formations contain very old porewater. However, the possibility of mixing of young water was indicated because He concentration was lower than that calculated by multiplication of in situ He production and time after the uplift. This possibility was also supported by Cl − , δ D, and δ 18 O data. After combining information on 36 Cl/Cl, 4 He, and δ D and δ 18 O, it was inferred that the porewater in the deep part of the Wakkanai Formation might have been stagnant since the uplift. The porewater in the Koetoi Formation and the shallow part of the Wakkanai Formation were found to be affected by young surface water.
Class I MHC-restricted cytotoxic T lymphocyte recognition of cells infected with human cytomegalovirus does not require endogenous viral gene expression (1991)

The human pathogen CMV, is a major cause of morbidity and mortality in immunocompromised hosts. The CD8+ class I-restricted CTL response to CMV assists in preventing progression of CMV infection to life-threatening disease; however, the viral Ag recognized by CD8+ CTL are not well characterized. In general, virus-specific CTL recognize endogenously synthesized viral proteins processed and presented associated with class I MHC molecules. Although proteins or inactivated virions have been experimentally delivered to the cytoplasm to result in class I MHC presentation, this mode of Ag delivery to the class I processing pathway after natural viral entry has not been documented in humans. Our data demonstrate that the CMV-specific class I-restricted CTL response in individuals latently infected with CMV is predominantly specific for selected structural virion proteins introduced into the cell after viral penetration and efficient recognition occurs in the absence of de novo viral gene expression. This CTL response may provide a biological advantage for limiting the spread of infection after CMV reactivation because infected cells are lysed before viral assembly.
IL-13 Activates a Mechanism of Tissue Fibrosis That Is Completely TGF-β Independent (2004)

Fibrosis is a characteristic feature in the pathogenesis of a wide spectrum of diseases. Recently, it was suggested that IL-13-dependent fibrosis develops through a TGF-beta1 and matrix metalloproteinase-9-dependent (MMP-9) mechanism. However, the significance of this pathway in a natural disorder of fibrosis was not investigated. In this study, we examined the role of TGF-beta in IL-13-dependent liver fibrosis caused by Schistosoma mansoni infection. Infected IL-13-/- mice showed an almost complete abrogation of fibrosis despite continued and undiminished production of TGF-beta1. Although MMP-9 activity was implicated in the IL-13 pathway, MMP-9-/- mice displayed no reduction in fibrosis, even when chronically infected. To directly test the requirement for TGF-beta, studies were also performed with neutralizing anti-TGF-beta Abs, soluble antagonists (soluble TGF-betaR-Fc), and Tg mice (Smad3-/- and TGF-betaRII-Fc Tg) that have disruptions in all or part of the TGF-beta signaling cascade. In all cases, fibrosis developed normally and with kinetics similar to wild-type mice. Production of IL-13 was also unaffected. Finally, several genes, including interstitial collagens, several MMPs, and tissue inhibitors of metalloprotease-1 were up-regulated in TGF-beta1-/- mice by IL-13, demonstrating that IL-13 activates the fibrogenic machinery directly. Together, these studies provide unequivocal evidence of a pathway of fibrogenesis that is IL-13 dependent but TGF-beta1 independent, illustrating the importance of targeting IL-13 directly in the treatment of infection-induced fibrosis.
Accepting its Random Coil Nature Allows a Partial NMR Assignment of the Neuronal Tau Protein (2004)

A combined strategy to obtain a partial NMR assignment of the neuronal Tau protein is presented. Confronted with the extreme spectral degeneracy that the spectrum of this 441 amino acid long unstructured protein presents, we have introduced a graphical procedure based on residue type-specific product planes. Combining this strategy with the search for pairwise motifs, and combining the spectra of different Tau isoforms and even of peptides derived from the native sequence, we arrive at a partial assignment that is sufficient to map the interactions of Tau with its molecular partners. The obtained assignments equally confirm the absence of regular secondary structure in the isolated protein.
Cytochrome P450-generated metabolites derived from ω-3 fatty acids attenuate neovascularization (2014)

Ocular neovascularization, including age-related macular degeneration (AMD), is a primary cause of blindness in individuals of industrialized countries. With a projected increase in the prevalence of these blinding neovascular diseases, there is an urgent need for new pharmacological interventions for their treatment or prevention. Increasing evidence has implicated eicosanoid-like metabolites of long-chain polyunsaturated fatty acids (LCPUFAs) in the regulation of neovascular disease. In particular, metabolites generated by the cytochrome P450 (CYP)-epoxygenase pathway have been shown to be potent modulators of angiogenesis, making this pathway a reasonable previously unidentified target for intervention in neovascular ocular disease. Here we show that dietary supplementation with ω-3 LCPUFAs promotes regression of choroidal neovessels in a well-characterized mouse model of neovascular AMD. Leukocyte recruitment and adhesion molecule expression in choroidal neovascular lesions were down-regulated in mice fed ω-3 LCPUFAs. The serum of these mice showed increased levels of anti-inflammatory eicosanoids derived from eicosapentaenoic acid and docosahexaenoic acid. 17,18-epoxyeicosatetraenoic acid and 19,20-epoxydocosapentaenoic acid, the major CYP-generated metabolites of these primary ω-3 LCPUFAs, were identified as key lipid mediators of disease resolution. We conclude that CYP-derived bioactive lipid metabolites from ω-3 LCPUFAs are potent inhibitors of intraocular neovascular disease and show promising therapeutic potential for resolution of neovascular AMD.
Interactive Phrasebook - Embedding Human Social Dynamics in Language Training (2010)

Today, many individuals must interact with others who not only use different languages, but have fundamentally different belief structures and concepts of trust and collaboration. While proficiency in a language is important, it is only one aspect of effective communication. Knowledge about culturally influenced social norms, or etiquette, directly impacts interaction outcomes. Computer-based training systems are a promising and cost effective solution for providing simulated social interactions for a learner to both practice language use and observe cultural nuances in the dynamics of an interaction. A computerized actor which displays social characteristics consistent with its cultural background can provide low cost training and rehearsal opportunities. Such a system would allow humans to train with realistically-behaving simulations in high fidelity situational contexts, and interactions with virtual agents that reflect the types of people they will be required to work with. The authors have adapted a well grounded socio-linguistic model of human-human interaction, and applied it in a language and culture training application. Interactive Phrasebook leverages work in a scalable, customizable, and computationally tractable model of a universal code of conduct that defines how social dynamics such as power and social distance manifests into the expression and interpretation of interaction behaviors.
Trifluoromethanesulfanylamides as Easy‐to‐Handle Equivalents of the Trifluoromethanesulfanyl Cation (CF3S+): Reaction with Alkenes and Alkynes (2009)

Making introductions: The CF3S unit can be added in an electrophilic fashion to alkenes and alkynes in reactions with trifluoromethanesulfanylamide reagents (see scheme; Ts=toluene-4-sulfonyl). The products obtained may be of interest, for example, in pharmaceutical chemistry and materials science.
Comparison of the membrane binding kinetics of bovine prothrombin and its fragment 1. (1993)

Total internal reflection fluorescence microscopy has been used to compare the membrane binding characteristics of fluorescein-labeled bovine prothrombin and fluorescein-labeled bovine prothrombin fragment 1. The Ca(2+)-dependent association of these proteins with quartz-supported planar membranes composed of mixtures of phosphatidylserine (2-10 mol%) and phosphatidylcholine was examined. Equilibrium binding measurements showed that the apparent equilibrium dissociation constants increased with decreasing molar fractions of phosphatidylserine and that the dissociation constants were somewhat lower for intact prothrombin. Kinetic measurements, using fluorescence photobleaching recovery, showed that the measured dissociation rates were approximately equivalent for prothrombin and fragment 1 and did not change with the protein solution concentration or the molar fraction of phosphatidylserine. The kinetic data also implied that the surface binding mechanism for both proteins is more complex than a simple reversible reaction between monovalent proteins and monovalent surface sites. Measured equilibrium and kinetic constants are reported and compared for prothrombin and fragment 1 on planar membranes.
Three-level fiber DFB laser at 980 nm (2004)

A three-level fiber DFB-laser operating at 977nm is demonstrated for the first time using a 910nm pump diode. The fiber DFB laser shows 17.5mW output power under a launching power of 113mW.
Promise for plant pest control: root-associated pseudomonads with insecticidal activities (2013)

Insects are an important and probably the most challenging pest to control in agriculture, in particular when they feed on belowground parts of plants. The application of synthetic pesticides is problematic owing to side effects on the environment, concerns for public health and the rapid development of resistance. Entomopathogenic bacteria, notably Bacillus thuringiensis and Photorhabdus/Xenorhabdus species, are promising alternatives to chemical insecticides, for they are able to efficiently kill insects and are considered to be environmentally sound and harmless to mammals. However, they have the handicap of showing limited environmental persistence or of depending on a nematode vector for insect infection. Intriguingly, certain strains of plant root-colonizing Pseudomonas bacteria display insect pathogenicity and thus could be formulated to extend the present range of bioinsecticides for protection of plants against root-feeding insects. These entomopathogenic pseudomonads belong to a group of plant-beneficial rhizobacteria that have the remarkable ability to suppress soil-borne plant pathogens, promote plant growth, and induce systemic plant defenses. Here we review for the first time the current knowledge about the occurrence and the molecular basis of insecticidal activity in pseudomonads with an emphasis on plant-beneficial and prominent pathogenic species. We discuss how this fascinating Pseudomonas trait may be exploited for novel root-based approaches to insect control in an integrated pest management framework.
Lipid association, but not the transmembrane domain, is required for tissue factor activity. Substitution of the transmembrane domain with a phosphatidylinositol anchor. (1991)

Full-length tissue factor (263 rTF) and three truncated forms have been expressed in human kidney 293 cells; 1) 243 rTF, which lacks the cytoplasmic tail, is fully functional in the chromogenic assay and has a specific activity comparable with that of the full-length molecule, 263 rTF; 2) 219 rTF, which lacks both the transmembrane and cytoplasmic domains, is not functional; 3) the third variant, referred to as TF-PI, is a fusion protein containing the extracellular domain of TF (amino acids 1-219) fused to the last 37 amino acids of decay-accelerating factor which contain a signal for attachment of a phosphatidylinositol membrane anchor (PI). TF-PI is a membrane-bound protein expressed on the cell surface. The PI anchor restores TF activity lost when the transmembrane domain is deleted from the 219 rTF variant. The ability of the PI anchor to restore activity to 219 rTF clearly demonstrates that while the transmembrane domain is not required for TF activity, lipid association is required.