gebhart/patrepeval huggingface dataset:
Apatite coated on organic polymers by biomimetic process: Improvement in its adhesion to substrate by glow‐discharge treatment (1995)

A dense, uniform, and highly biologically active bone-like apatite layer can be formed in arbitrary thickness on any kind and shape of solid substrate surface by the following biomimetic method at ordinary temperature and pressure: First, a substrate is set in contact with particles of bioactive CaO-SiO2-based glass soaked in a simulated body fluid (SBF) with inorganic ion concentrations nearly equal to those of human blood plasma so that a number of apatite nuclei are formed on the substrate. Second, the substrate is soaked in another solution with ion concentrations 1.5 times those of SBF (1.5SBF) so that the apatite nuclei grow in situ. In the present study, organic polymer substrates were treated with glow-discharge in O2 gas atmosphere, then subjected to the above-mentioned biomimetic process. The induction periods for the apatite nucleation on all the examined organic polymers were reduced from 24 to 6 h, with glow-discharge treatment. The adhesive strengths of the formed apatite layer to the substrates increased from about 4 to 10 MPa for poly(ethylene terephthalate) and poly-ether sulfone, and from 1 approximately 2 to 6 approximately 7 MPa even for poly(methyl methacrylate), polyamide 6 and polyethylene. It is supposed that highly polar groups such as carbonyl, ester, hydroxyl, and carboxyl ones formed by glow-discharge treatment increased the affinity of a silicate ion with the substrates to decrease the induction period, and also increased the affinity of the apatite with the substrate to increase the adhesive strength.(ABSTRACT TRUNCATED AT 250 WORDS)
BH3 Profiling Discriminates Response to Cytarabine-Based Treatment of Acute Myelogenous Leukemia (2013)

As acute myelogenous leukemia (AML) patient response to cytarabine-based standard-of-care treatment is variable, stratification into subgroups by biomarker-predicted response may lead to improved clinical outcomes. Here, we assess cell mitochondrial depolarization to proapoptotic signaling BH3-only peptides as a surrogate for the function of Bcl-2 family proteins to address clinical response to cytarabine-based therapy in patients with AML (N = 62). Peripheral blood mononuclear cell (PBMC) or bone marrow aspirate specimens were obtained from newly diagnosed patients with AML, viably preserved, and assayed by flow cytometry following BH3 profile assay with individual BH3 peptides. Mann-Whitney analysis indicates biomarker correlation with response to induction therapy: Notably, BIM priming was highly significant (P = 2 × 10(-6)) with a compelling sensitivity/specificity profile [area under curve (AUC) = 0.83; 95% confidence interval (CI), 0.73-0.94; P = 2 × 10(-10)]. Multivariate analysis indicates improved profiles for BIM readout + patient age (AUC = 0.89; 95% CI, 0.81-0.97) and BIM + patient age + cytogenetic status (AUC = 0.91; 95% CI, 0.83-0.98). When patients were stratified by cytogenetic status, BIM readout was significant for both intermediate (P = 0.0017; AUC = 0.88; 95% CI, 0.71-1.04) and unfavorable (P = 0.023; AUC = 0.79; 95% CI, 0.58-1.00) risk groups, demonstrating predictive power independent of cytogenetics. Additional analyses of secondary clinical endpoints displayed correlation between overall survival (P = 0.037) and event-free survival (P = 0.044) when patients were stratified into tertiles by BIM peptide response. Taken together, these results highlight the potential utility of BH3 profiling in personalized diagnostics of AML by offering actionable information for patient management decisions.
Dispersion and Functionalization of Nonaqueous Synthesized Zirconia Nanocrystals via Attachment of Silane Coupling Agents (2008)

Zirconia (ZrO 2) nanocrystals, synthesized from zirconium(IV) isopropoxide isopropanol complex and benzyl alcohol, were dispersed and functionalized in organic solvents using three kinds of bifunctional silane coupling agents (SCAs), 3-glycidoxypropyltrimethoxysilane (GPTMS), 3-aminopropyltriethoxysilane (APTES), and 3-isocyanatopropyltriethoxysilane (IPTES). Completely transparent ZrO 2 dispersions were achieved in tetrahydrofuran (THF) with all three SCAs, in pyridine and toluene with APTES and IPTES, and in N, N-dimethylformamide with IPTES. Dynamic laser scattering (DLS) measurements and high-resolution transmission electron microscopical (HRTEM) observation indicated that the ZrO 2 nanocrystals are dispersed on a primary particle size level. Fourier transform infrared spectroscopy, solid-state (13)C- and (29)Si NMR spectroscopy, and thermogravimetric analysis demonstrated that all three SCAs are chemically attached to the surface of the ZrO 2 nanoparticles, however, in different bonding modes. Except for GPTMS/ZrO 2/THF dispersion and IPTES/ZrO 2/pyridine dispersion, all other transparent dispersions have poor long-term stability. The increasing polarity, due to high amount of APTES attached and high hydrolysis and condensation degree of the bonded APTES, and the aggregation, due to interparticle coupling via the bonded triethoxysilyl group, are the causes of the poor long-term stability for the ZrO 2 dispersions with APTES and IPTES, respectively. Nevertheless, the APTES-functionalized ZrO 2 precipitates can be deagglomerated in water to get a stable and transparent aqueous ZrO 2 dispersion via addition of a little hydrochloric acid.
Cryptococcus neoformans serotype A glucuronoxylomannan-protein conjugate vaccines: synthesis, characterization, and immunogenicity (1991)

We synthesized Cryptococcus neoformans serotype A glucuronoxylomannan (GXM) conjugate vaccines under conditions suitable for human use to prevent disseminated cryptococcosis. The purified, sonicated GXM was derivatized with adipic acid dihydrazide through either hydroxyl or carboxyl groups and then covalently bound to tetanus toxoid (TT) or Pseudomonas aeruginosa exoprotein A (rEPA). The immunogenicity of these conjugates was evaluated in BALB/c and general purpose mice by subcutaneous injection in saline. The conjugates elicited higher GXM antibody responses than GXM alone. Booster immunoglobulin G (IgG) and IgM responses were elicited by all conjugates in BALB/c mice. The conjugates prepared through hydroxyl activation (GXM-TT2 and GXM-rEPA) were more immunogenic than the one prepared through carboxyl activation (GXM-TT1). GXM antibody response was enhanced by the administration of monophosphoryl lipid A 2 days following the injection of GXM-TT2 (P less than 0.03). The conjugates also elicited IgG antibodies to the carrier proteins. Gel diffusion tests using conjugate-induced hyperimmune sera and chemically modified GXMs suggested that the specificity of GXM-TT1-induced antibodies was conferred by the O-acetyl groups. Hyperimmune sera generated by GXM-TT2 precipitated with the chemically unmodified and the de-O-acetylated GXMs but not with the carboxyl-reduced and de-O-acetylated GXM. GXM-TT2-induced hyperimmune serum also precipitated with the capsular polysaccharides of C. neoformans serotypes D, B, and C. The conjugate vaccines prepared through hydroxyl activation of the GXM are sufficiently immunogenic and appear to be suitable for clinical evaluation.
Transfer of a β-Hairpin from the Functional Site of Snake Curaremimetic Toxins to the α/β Scaffold of Scorpion Toxins:  Three-Dimensional Solution Structure of the Chimeric Protein, (1996)

The alpha/beta scorpion fold is shared by scorpion toxins, insect defensins, and plant thionins. This small and functionally versatile template contains an alpha-helix and a triple beta-sheet linked by three disulfide bridges. With the view to introduce novel functional centers within this fold, we replaced the sequence (the cysteines and glycines excepted) of the original beta-hairpin of a scorpion toxin by the sequence of a beta-hairpin that forms part of the site by which snake neurotoxins bind to nicotinic acetylcholine receptors (AcChOR). The resulting chimeric protein, synthesized by chemical means, binds to AcChOR, though with a lower affinity than the snake toxins [Drakopoulou; E., Zinn-Justin, S., Guenneugues, M., Gilquin, B., Ménez, A., & Vita, C. (1996) J. Biol. Chem. 271, 11979-11987]. The work described in this paper is an attempt to clarify the structural consequences associated with the transfer of the beta-hairpin. We report the determination of the three-dimensional solution structure of the chimeric protein by proton NMR spectroscopy and molecular dynamics calculations. Comparison of the structure of the chimera with those of the scorpion alpha/beta toxin and of the snake neurotoxin shows that (i) the new protein folds as an alpha/beta motif and (ii) the beta-hairpins of the chimera and of the curaremimetic toxin adopt a similar conformation. A closer inspection of the differences between the structures of the original and transferred beta-hairpins allows rationalization of the biological properties of the chimera.
C-Reactive Protein Binds to Apoptotic Cells, Protects the Cells from Assembly of the Terminal Complement Components, and Sustains an Antiinflammatory Innate Immune Response (2000)

C-reactive protein (CRP) is a serum protein that is massively induced as part of the innate immune response to infection and tissue injury. As CRP has been detected in damaged tissues and is known to activate complement, we assessed whether apoptotic lymphocytes bound CRP and determined the effect of binding on innate immunity. CRP bound to apoptotic cells in a Ca(2+)-dependent manner and augmented the classical pathway of complement activation but protected the cells from assembly of the terminal complement components. Furthermore, CRP enhanced opsonization and phagocytosis of apoptotic cells by macrophages associated with the expression of the antiinflammatory cytokine transforming growth factor beta. The antiinflammatory effects of CRP required C1q and factor H and were not effective once cells had become necrotic. These observations demonstrate that CRP and the classical complement components act in concert to promote noninflammatory clearance of apoptotic cells and may help to explain how deficiencies of the classical pathway and certain pentraxins lead to impaired handling of apoptotic cells and increased necrosis with the likelihood of immune response to self.
3-Arylcoumarin Derivatives Manifest Anti-proliferative Activity through Hsp90 Inhibition (2012)

The potential therapeutic benefits associated with Hsp90 modulation for the treatment of cancer and neurodegenerative diseases highlight the importance of identifying novel Hsp90 scaffolds. KU-398, a novobiocin analogue, and silybin were recently identified as new Hsp90 inhibitors. Consequently, a library of 3-arylcoumarin derivatives that incorporated the structural features of KU-398 and silybin was designed, synthesized and evaluated against two breast cancer cell lines. Western blot analysis confirmed that the resulting 3-arylcoumarin hybrids target the Hsp90 protein folding machinery.
Immune mechanisms of Concanavalin A model of autoimmune hepatitis (2012)

As a chronic inflammatory disease of the liver, the pathogenic mechanisms of autoimmune hepatitis (AIH) have not yet been elucidated, with prognosis and diagnosis remaining unsatisfied. Currently the only viable treatments of AIH are immunosuppressant application and liver transplantation. It is considered that lack of good animal AIH models is the main reason for the shortage of a simple and efficient cure. The Concanavalin A (Con A) model is a typical and well established model for investigating T-cell and macrophage dependent liver injury in mice, which closely mimics the pathogenesis mechanisms and pathological changes of patients, and is regarded as the best experimental model for AIH research so far. In this paper we elucidated the pathogenic mechanisms of AIH and the evolution of relative animal models. We go on to further focus on Con A-induced liver injury from the point of immunological mechanisms and the change of cytokine levels. Finally, we manifested the clinical significance of the AIH animal models and the challenges they would meet during their future development.
SEMA3A partially reverses VEGF effects through binding to neuropilin-1 (2017)

Cross-talk between hematopoietic stem cells (HSCs) and bone marrow stromal cells (BMSCs) is essential for HSCs regulation and leukemogenesis. Studying bone marrow of myelodysplasia patients, a pre-leukemic condition, we found mRNA overexpression of vascular endothelial growth factor A (VEGFA) in CD34<sup>+</sup> HSCs and semaphorin 3A (SEMA3A) in BMSCs. To better understand the role of VEGFA and SEMA3A in leukemogenesis, we recruited 30 myelodysplastic syndrome (MDS) patients, 29 acute myeloid leukemia (6 secondary to MDS) patients and 12 controls. We found higher VEGFA expression in de novo AML patients (without prior MDS) group (p=0.0073) and higher SEMA3A expression in all BMSCs patient's samples compared to control group. We then overexpressed VEGFA in an acute myelogenous leukemia cell line, KG1 cells, and in normal CD34<sup>+</sup> cells. This overexpression increased KG1 (p=0.045) and CD34<sup>+</sup> cell (p=0.042) viability and KG1 (p=0.042) and CD34<sup>+</sup> cell (p=0.047) proliferation. Moreover, KG1 and CD34<sup>+</sup> cells overexpressing VEGFA also had increased proliferation when co-cultured with human marrow stromal HS5 cells (p=0.045 and p=0.02, respectively). However, co-culture of these transformed cells with HS5 cells overexpressing SEMA3A reduced KG1 (p=0.004) and CD34<sup>+</sup> (p=0.009) proliferation. Co-culture of KG1 transformed cells with HS27 cells overexpressing SEMA3A reduced KG1 proliferation as well (p=0.01). To investigate whether the dominant SEMA3A effect over VEGFA could be due to competition for neuropilin1 receptor (NRP1), we performed immunoprecipitation with anti-NRP1 antibody of cell extracts of co-cultured KG1 and HS5 cells, induced or not by VEGFA and SEMA3A recombinant proteins. Results showed a preferential association of NRP1 with SEMA3A, suggesting that SEMA3A can partially reverse the effects caused by the VEGFA preventing its binding with the NRP1 receptor. Since both hematopoietic cells, leukemic and normal, showed similar behavior, we suppose that the attempt to reversion of VEGF effects by SEMA3A is a homeostatic phenomenon in the hematopoietic niche. Finally, we conclude that VEGFA overexpression confers AML cell advantages and SEMA3A may partially reverse this effect; thus, SEMA3A protein combined with VEGFA inhibitors could be beneficial for AML treatment.
From Determinants of RUNX1/ETO Tetramerization to Small-Molecule Protein–Protein Interaction Inhibitors Targeting Acute Myeloid Leukemia (2013)

We identified the first small-molecule protein-protein interaction inhibitors of RUNX1/ETO tetramerization applying structure-based virtual screening guided by predicted hot spots and pockets in the interface. A 3D similarity screening revealed specific hot spot mimetics, one of which prevents the proliferation of RUNX1/ETO-dependent SKNO-1 cells at low micromolar concentration. Using solely a protein-protein complex structure to start with, this strategy can be the first step in any comparable structure-based endeavor to identify protein-protein interaction inhibitors.
Design, synthesis, and testing of potential antisickling agents. 10. 2,2-Dimethylchroman-6-ylalkanoic acids (1987)

Five (2,2-dimethylchroman-6-yl)alkanoic acids were synthesized and tested for antigelling activities. It was envisioned that these agents might bind via hydrophobic bonding to nonpolar sites of the "donor-acceptor" regions of hemoglobin S. Several (2,2-dimethylchroman-6-yl)alkanoic acids containing 1-4 carbon atoms on the side-chain residue were designed to interact at the acceptor site, were synthesized, and were found to be moderately potent antigelling agents. The weak activity observed for two of the acids at low concentrations is rationalized in terms of weak binding affinities or multiple binding to active and nonactive sites. The effect of these compounds on shifting the allosteric equilibrium was small or negligible. The low toxicity of one of the (2,2-dimethylchroman-6-yl)alkanoic acids demonstrates the potential use of yet another class of compounds that can be modified in the development of antisickling agents.
Carotenoids as colorants and vitamin A precursors : technological and nutritional applications (1981)

List of Contributors. Foreword. Preface. Natural Food Colors, J.C. Bauernfeind. Carotenoids as Food Color, H. Klaui and J.C. Bauernfeind. Oxycarotenoids in Poultry Feed, W.L. Marusich and J.C. Bauernfeind. Carotenoids in Fish Feeds, K.L. Simpson, T. Katayama, and C.O. Chichester. Carotenoids in Wild and Captive Birds, A.H. Brush. Carotenes and Other Vitamin A Precursors in Animal Feed, J.C. Bauernfeind, C.R. Adams, and W.L. Marusich. Carotenoids in Pharmaceutical and Cosmetic Products, K. Munzel. Carotenoids in Medical Applications, M.M. Mathews-Roth. Carotenoids as Photoconductors, J.O. Williams. Carotenoid Analytical Methods, E. De Ritter and A.E. Purcell. Index.
Pd-Catalyzed Copper-Free Carbonylative Sonogashira Reaction of Aryl Iodides with Alkynes for the Synthesis of Alkynyl Ketones and Flavones by Using Water as a Solvent (2005)

The Pd-catalyzed copper-free carbonylative Sonogashira coupling reaction to synthesize alkynyl ketones from terminal alkynes and aryl iodides was achieved by using water as a solvent. The reaction was carried out at room temperature under balloon pressure of CO with Et(3)N as a base. The developed method was successfully applied to the synthesis of flavones.
CCN3: a key growth regulator in Chronic Myeloid Leukaemia (2009)

Chronic Myeloid Leukaemia (CML) is characterized by expression of the constitutively active Bcr-Abl tyrosine kinase. We have shown previously that the negative growth regulator, CCN3, is down-regulated as a result of Bcr-Abl kinase activity and that CCN3 has a reciprocal relationship of expression with BCR-ABL. We now show that CCN3 confers growth regulation in CML cells by causing growth inhibition and regaining sensitivity to the induction of apoptosis. The mode of CCN3 induced growth regulation was investigated in K562 CML cells using gene transfection and treatment with recombinant CCN3. Both strategies showed CCN3 regulated CML cell growth by reducing colony formation capacity, increasing apoptosis and reducing ERK phosphorylation. K562 cells stably transfected to express CCN3 showed enhanced apoptosis in response to treatment with the tyrosine kinase inhibitor, imatinib. Whilst CCN3 expression was low or undetectable in CML stem cells, primary CD34+ CML progenitors were responsive to treatment with recombinant CCN3. This study shows that CCN3 is an important growth regulator in haematopoiesis, abrogation of CCN3 expression enhances BCR-ABL dependent leukaemogenesis. CCN3 restores growth regulation, regains sensitivity to the induction of apoptosis and enhances imatinib cell kill in CML cells. CCN3 may provide an additional therapeutic strategy in the management of CML.
Methylation status of uPA promoter as a molecular mechanism regulating prostate cancer invasion and growth in vitro and in vivo (2003)

Urokinase plasminogen activator (uPA) promotes tumor invasion and metastasis in several malignancies including prostate cancer, one of the most commonly detected male cancers that result in a high incidence of mortality. In the present study we have examined the differential regulation of uPA gene expression in different stages of prostate cancer by DNA methylation. We determined levels of uPA expression in normal prostate epithelial cells (PrEC) and in hormone-responsive (LNCaP) and -insensitive (PC-3) prostate cancer cell lines. We found that uPA is expressed only in the highly invasive PC-3 cells where the uPA promoter is unmethylated. The lack of uPA expression in PrEC and LNCaP cells, where uPA promoter is highly methylated, is due to suppression of uPA gene transcription by DNA methylation. Treatment of LNCaP cells with 5'-azacytidine, a potent demethylating agent, resulted in induction of uPA mRNA expression, uPA activity, and higher invasive capacity in vitro. Additionally, a marked increase in tumor volume was observed after inoculation of these cells into the flank of male BALB/c (nu/nu) mice. Collectively these studies have demonstrated that DNA methylation is the underlying molecular mechanism responsible for uPA gene silencing in normal and early stages of prostate cancer, which has a direct effect on tumor cell invasion and growth in vitro and in vivo.
A Central Role for Free Heme in the Pathogenesis of Severe Sepsis (2010)

Low-grade polymicrobial infection induced by cecal ligation and puncture is lethal in heme oxygenase-1-deficient mice (Hmox1(-/-)), but not in wild-type (Hmox1(+/+)) mice. Here we demonstrate that the protective effect of this heme-catabolizing enzyme relies on its ability to prevent tissue damage caused by the circulating free heme released from hemoglobin during infection. Heme administration after low-grade infection in mice promoted tissue damage and severe sepsis. Free heme contributed to the pathogenesis of severe sepsis irrespective of pathogen load, revealing that it compromised host tolerance to infection. Development of lethal forms of severe sepsis after high-grade infection was associated with reduced serum concentrations of the heme sequestering protein hemopexin (HPX), whereas HPX administration after high-grade infection prevented tissue damage and lethality. Finally, the lethal outcome of septic shock in patients was also associated with reduced HPX serum concentrations. We propose that targeting free heme by HPX might be used therapeutically to treat severe sepsis.
The 2.9 Å Crystal Structure of T. thermophilus Seryl-tRNA Synthetase Complexed with tRNA Ser (1994)

The crystal structure of Thermus thermophilus seryl-transfer RNA synthetase, a class 2 aminoacyl-tRNA synthetase, complexed with a single tRNA(Ser) molecule was solved at 2.9 A resolution. The structure revealed how insertion of conserved base G20b from the D loop into the core of the tRNA determines the orientation of the long variable arm, which is a characteristic feature of most serine specific tRNAs. On tRNA binding, the antiparallel coiled-coil domain of one subunit of the synthetase makes contacts with the variable arm and T psi C loop of the tRNA and directs the acceptor stem of the tRNA into the active site of the other subunit. Specificity depends principally on recognition of the shape of tRNA(Ser) through backbone contacts and secondarily on sequence specific interactions.
The Preparation of Tissue-Type Plasminogen Activator (t-PA) Containing Liposomes: Entrapment Efficiency and Ultracentrifugation Damage (1995)

almost quantitative t-PA entrapment in liposomes can be achieved by selecting the proper milieu and inducing a strong interaction between t-PA and bilayer.