gebhart/patrepeval huggingface dataset:
Polyphosphazenes: Effect of molecular motions on thrombogenesis (1982)

The effect and interrelationship between primary (segmental backbone) and secondary (side chain) molecular motions on thrombogenesis, independent of morphological order/disorder, crystallinity, and/or associated water is elucidated using an amorphous hydrophobic polymer of poly-[(trifluoroethoxy) (fluoroalkoxy)phosphazene] PNF. The results indicate that thrombogenesis for an amorphous hydrophobic polymer is sensitive and dependent on the degrees and types of primary and secondary molecular motions at the polymer interface.
Degraded text recognition using word collocation and visual inter-word constraints (1994)

Given a noisy text page, a word recognizer can generate a set of candidates for each word image. A relaxation algorithm was proposed previously by the authors that uses word collocation statistics to select the candidate for each word that has the highest probability of being the correct decision. Because word collocation is a local constraint and collocation data trained from corpora are usually incomplete, the algorithm cannot select the correct candidates for some images. To overcome this limitation, contextual information at the image level is now exploited inside the relaxation algorithm. If two word images can match with each other, they should have same symbolic identity. Visual inter-word relations provide a way to link word images in the text and to interpret them systematically. By integrating visual inter-word constraints with word collocation data, the performance of the relaxation algorithm is improved.
Extracellular matrix histone H1 binds to perlecan, is present in regenerating skeletal muscle and stimulates myoblast proliferation (2002)

Heparan sulfate chains of proteoglycans bind to and regulate the function of a wide variety of ligands. In myoblasts, heparan sulfate proteoglycans modulate basic fibroblast growth factor activity and regulate skeletal muscle differentiation. The aim of this study was to identify endogenous extracellular ligands for muscle cell heparan sulfate proteoglycans. [(35)S]heparin ligand blot assays identified a 33/30 kDa doublet (p33/30) in detergent/high ionic strength extracts and heparin soluble fractions obtained from intact C(2)C(12) myoblasts. p33/30 is localized on the plasma membrane or in the extracellular matrix where its level increases during muscle differentiation. Heparin-agarose-purified p33/30 was identified as histone H1. In vitro binding assays showed that histone H1 binds specifically to perlecan. Immunofluorescence microscopy showed that an extracellular pool of histone H1 colocalizes with perlecan in the extracellular matrix of myotube cultures and in regenerating skeletal muscle. Furthermore, histone H1 incorporated into the extracellular matrix strongly stimulated myoblast proliferation via a heparan-sulfate-dependent mechanism. These results indicate that histone H1 is present in the extracellular matrix of skeletal muscle cells, where it interacts specifically with perlecan and exerts a strong proliferative effect on myoblasts, suggesting a role for histone H1 during skeletal muscle regeneration.
Evidence for the ontogenic precedence of suppressor T cell functions in the human neonate (1983)

Abstract The study was undertaken to elucidate some functional characteristics of T cell subsets in human cord blood. A comparison of the cellular interactions involved in the in vitro regulation of pokeweed (PWM) vs . Epstein‐Barr virus (EBV)‐driven B cell differentiation was done in vitro in short‐term cultures of lymphocytes from newborns or adults. T cell subsets were isolated using the monoclonal antibodies OKT4 + and OKT8 + . OKT4 + but not OKT8 + T lymphocytes from adults as well as neonates suppressed EBV‐induced immunoglobulin (Ig) secretion of B lymphocytes from adults. This inhibition was mediated through gamma‐type interferon (IFN‐γ). B cells from newborns were not inhibitable by OKT4 + lymphocytes as a result of their insensitivity to IFN‐γ. Helper activity for PWM‐induced Ig secretion was exclusively contained within the OKT4 + population from adult T cell donors. This function was normally not detectable in any of the neonatal T cell subsets. OKT8 + cells from both adults and neonates suppressed PWM‐induced Ig secretion, but required the collaboration with cells within the OKT4 + population. The suppressor activity in the PWM system was not IFN‐γ‐mediated. Thus, suppressor functions for EBV‐ vs . PWM‐induced Ig synthesis were mediated through different pathways. There was no evidence of a unique suppressor system in the newborn. In the neonate, suppressor T cell activities are developed before T helper functions, a circumstance for which there is good evolutionary reason.
INDUCTION OF TRANSPLANTATION TOLERANCE IN ADULTS USING DONOR ANTIGEN AND ANTI-CD4 MONOCLONAL ANTIBODY (1992)

The T-cell-mediated immune response usually results in the rapid destruction of organ allografts transplanted between murine strains incompatible for major and minor histocompatibility antigens. This response may be modified by pretreatment with either donor-specific antigen or anti-CD4 monoclonal antibody. Previous work by others has shown that combined treatment of mice with soluble protein antigens and anti-CD4 monoclonal antibody can produce antigen-specific B cell unresponsiveness that continues long after the nonspecific immunosuppressive effect of the mAb treatment has resolved. Following this principle we have shown that adult C3H/He mice can be made specifically unresponsive to vascularized C57BL/10 cardiac allografts by pretreating the recipient with donor alloantigen under the cover of a brief course of mAb against CD4. A full-dose response analysis shows that the dose of mAb is critically important for the successful induction of tolerance. Tolerance induction using this protocol is dependent on treatment with donor major histocompatibility complex antigens and occurs in the presence of marked depletion but not complete elimination of the CD4+ T cell subset. The unresponsiveness to alloantigen is antigen specific, as determined by the ineffectiveness of third-party (C57BL/10) alloantigen when combined with anti-CD4 mAb to induce long-term survival of BALB/c allografts in C3H/He recipients. The tolerant state is specific and effective in the long-term as indicated by the specific acceptance of C57BL/10 skin grafts in recipients with surviving C57BL/10 cardiac allografts. This study provides a simple method for the successful induction of specific transplantation tolerance in the adult across a full H-2 major and minor antigen mismatch strain combination. The results illustrate the important role of the CD4 molecule in the T cell response to alloantigen in vivo and suggest possibilities for the therapeutic manipulation of complex immune reactions.
Membrane Disrupting Lytic Peptides for Cancer Treatments (2004)

Membrane disrupting lytic peptides are abundant in nature and serve insects, invertebrates, vertebrates and humans as defense molecules. Initially, these peptides attracted attention as antimicrobial agents; later, the sensitivity of tumor cells to lytic peptides was discovered. In the last decade intensive research has been conducted to determine how lytic peptides lyse bacteria and tumor cells. A number of synthetic peptides have been designed to optimize their antibiotic and anti-tumor properties and improve their therapeutic capabilities. The sequences of alpha-helical cationic membrane disrupting peptides has been discussed, their proposed mechanisms of action reviewed, and their roles in cell selectivity and tumor cell destruction considered. Parameters important for the selection and design of lytic peptides for cancer treatments include increased activities against tumor cells, low cytolytic activities to normal mammalian cells and erythrocytes. The conjugation of lytic peptides with hormone ligands and the production of pro-peptides provide methods for targeting of cancer cells. The therapeutic possibilities in cancer treatment by targeted lytic peptides are broad and offer improvement to currently used chemotherapeutical drugs. Lytic peptides interact with the tumor cell membrane within minutes, and their activity is independent of multi-drug resistance. Lytic peptide-chorionic gonadotropin (CG) conjugates destroy primary tumors, prevent metastases and kill dormant and metastatic tumor cells. These conjugates do not destroy vital organs; they are not antigenic, and are more toxic to tumor cells than to non-malignant cells.
Antineoplastic Agents. 450. Synthesis of (+)-Pancratistatin from (+)-Narciclasine as Relay1a (2001)

(+)-Narciclasine (2) available in quantity from certain Amaryllidaceae species or by total synthesis was employed as a precursor for a 10-step synthetic conversion (3.6% overall yield) to natural (+)-pancratistatin (1a). The key procedures involved epoxidation of natural (+)-narciclasine (2) to epoxide 6, reduction to diol 8, and formation of cyclic sulfate 12 and its ring opening with cesium benzoate followed by saponification of the benzoate to afford (+)-pancratistatin (1a).
In Vivo Imaging of Caenorhabditis elegans Glycans (2009)

The nematode Caenorhabditis elegans is an excellent model organism for studies of glycan dynamics, a goal that requires tools for imaging glycans in vivo. Here we applied the bioorthogonal chemical reporter technique for the molecular imaging of mucin-type O-glycans in live C. elegans. We treated worms with azidosugar variants of N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), and N-acetylmannosamine (ManNAc), resulting in the metabolic labeling of their cell-surface glycans with azides. Subsequently, the worms were reacted via copper-free click reaction with fluorophore-conjugated difluorinated cyclooctyne (DIFO) reagents. We identified prominent localization of mucins in the pharynx of all four larval stages, in the adult hermaphrodite pharynx, vulva and anus, and in the tail of the adult male. Using a multicolor, time-resolved imaging strategy, we found that the distribution and dynamics of the glycans varied anatomically and with respect to developmental stage.
Effects of Basic Fibroblast Growth Factor on the Repair of Large Osteochondral Defects of Articular Cartilage in Rabbits: Dose–Response Effects and Long-Term Outcomes (2004)

Articular cartilage possesses a limited capacity for self-renewal. The regenerated tissue often resembles fibrocartilage-like tissue rather than hyaline cartilage, and degeneration of the articular surface eventually occurs. The purpose of this study was to investigate the effect of basic fibroblast growth factor (bFGF) on the healing of full-thickness articular cartilage defects. bFGF (0, 10, 50, 100, 250, 500, or 1000 ng) was mixed with collagen gel and implanted into full-thickness articular cartilage defects drilled into rabbit knees. The repaired tissue was examined grossly and histologically, and was evaluated with the use of a grading scale at 4, 12, 24, and 50 weeks. At 4 weeks, treatment with 100 ng of bFGF had greatly stimulated cartilage repair both grossly and histologically in comparison with untreated defects (those filled with plain collagen gel). The average total scores on the histological grading scale were significantly better for the defects treated with bFGF than for the untreated defects. These improvements were evident as long as 50 weeks postoperatively, although slight deterioration was noted in the repaired cartilage. Immunohistochemical staining for type II collagen showed that this cartilage-specific collagen was diffusely distributed in the repaired tissue at 50 weeks. These findings suggest that bFGF may be a practical and important candidate for use in cartilage repair.
Kinetics of Photopolymerization of Acrylates with Functionality of 1−6 (1999)

The photopolymerization of a number of neat acrylate monomers with acrylate functionality from 1−6 was studied with photoDSC (DSC = differential scanning calorimetry) and with a cure monitor using a fluorescent probe. PhotoDSC results show that conversion of monomers ranges from 40 to 100%, depending upon the functionality and structure of a monomer. Kinetics of a heat flow was well described as an autoaccelearted reaction for all monomers. Kinetics of the hardening of a sample under light at an ambient temperature was nicely fit into the two-exponential law; rate constants k1 and k2 in this empirical analysis were in the range of 0.5−35 min-1. The effect of an inhibitor and of air oxygen on kinetics of photopolymerization was also studied. The dependence of the rate of polymerization and conversion upon the functionality of a monomer is discussed.
Novel Series of Dihydropyridinone P2X7 Receptor Antagonists (2015)

Identification of singleton P2X7 inhibitor 1 from HTS gave a pharmacophore that eventually turned into potential clinical candidates 17 and 19. During development, a number of issues were successfully addressed, such as metabolic stability, plasma stability, GSH adduct formation, and aniline mutagenicity. Thus, careful modification of the molecule, such as conversion of the 1,4-dihydropyridinone to the 1,2-dihydropyridinone system, proper substitution at C-5″, and in some cases addition of fluorine atoms to the aniline ring allowed for the identification of a novel class of potent P2X7 inhibitors suitable for evaluating the role of P2X7 in inflammatory, immune, neurologic, or musculoskeletal disorders.
Transgenic Knockout Mice with Exclusively Human Sickle Hemoglobin and Sickle Cell Disease (1997)

To create mice expressing exclusively human sickle hemoglobin (HbS), transgenic mice expressing human alpha-, gamma-, and betaS-globin were generated and bred with knockout mice that had deletions of the murine alpha- and beta-globin genes. These sickle cell mice have the major features (irreversibly sickled red cells, anemia, multiorgan pathology) found in humans with sickle cell disease and, as such, represent a useful in vivo system to accelerate the development of improved therapies for this common genetic disease.
The AKT–mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells (2008)

CD4(+)Foxp3(+) regulatory T (T reg) cells play an essential role in maintaining immunological tolerance via their suppressive function on conventional CD4(+) T (Tconv) cells. Repertoire studies suggest that distinct T cell receptor signaling pathways lead to T reg differentiation, but the signals that regulate T reg specification are largely unknown. We identify AKT as a strong repressor of entry into the T reg phenotype in vitro and in vivo. A constitutively active allele of AKT substantially diminished TGF-beta-induced Foxp3 expression in a kinase-dependent manner and via a rapamycin-sensitive pathway, implicating the AKT-mammalian target of rapamycin axis. The observed impairment in Foxp3 induction was part of a broad dampening of the typical T reg transcriptional signature. Expression of active AKT at a stage before Foxp3 turn on during normal T reg differentiation in the thymus selectively impaired differentiation of CD4(+)Foxp3(+) cells without any alteration in the positive selection of Tconv. Activated AKT, in contrast, did not affect established Foxp3 expression in T reg cells. These results place AKT at a nexus of signaling pathways whose proper activation has a strong and broad impact on the onset of T reg specification.
Sensitization In Vitro to Murine Myeloblastic Leukemia Cells by Xenogeneic Immune RNA<xref ref-type="fn" rid="FN1">2</xref> (1979)

Theodore Roosevelt writes his son Kermit to talk about the Progressive Party Convention and family members who are attending and helping with the campaign. He says there is little hope he will beat Governor Woodrow Wilson but hopes to do better than President William Howard Taft and at least establish certain principles during the campaign.
Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. (1996)

The tet regulatory system in which doxycycline (dox) acts as an inducer of specifically engineered RNA polymerase II promoters was transferred into transgenic mice. Tight control and a broad range of regulation spanning up to five orders of magnitude were monitored dependent on the dox concentration in the water supply of the animals. Administration of dox rapidly induces the synthesis of the indicator enzyme luciferase whose activity rises over several orders of magnitude within the first 4 h in some organs. Induction is complete after 24 h in most organs analyzed. A comparable regulatory potential was revealed with the tet regulatory system where dox prevents transcription activation. Directing the synthesis of the tetracycline-controlled transactivator (tTA) to the liver led to highly specific regulation in hepatocytes where, in presence of dox, less than one molecule of luciferase was detected per cell. By contrast, a more than 10(5)-fold activation of the luciferase gene was observed in the absence of the antibiotic. This regulation was homogeneous throughout but stringently restricted to hepatocytes. These results demonstrate that both tetracycline-controlled transcriptional activation systems provide genetic switches that permit the quantitative control of gene activities in transgenic mice in a tissue-specific manner and, thus, suggest possibilities for the generation of a novel type of conditional mutants.
Clinical significance of galectin-7 in vulvar squamous cell carcinoma (2015)

The present study reports the role of galectin-7 (Gal-7) expression in vulvar squamous cell carcinoma (VSCC) and its correlation with clinicopathological variables. Gal-7 expression was immunohistochemically detected in the paraffin-embedded sections of 20 normal vulvar biopsy samples and 50 VSCC specimens. Expression was also detected in 10 normal vulvar biopsy samples and 10 VSCC specimens by western blotting. In addition, the methylation status of the promoter of the Gal-7 gene was determined in 30 VSCC specimens and 20 samples of normal vulvar tissue by methylation-specific polymerase chain reaction. Gal-7 expression was found to be significantly downregulated in the VSCC tissues compared with the normal vulvar tissues (P<0.05). Downregulation of Gal-7 was correlated with advanced clinical stage, poor tumor differentiation and regional lymph node metastasis (P<0.05). Furthermore, methylation of the Gal-7 gene promoter was significantly reduced in the vulvar normal tissues compared with the VSCC tissues (P=0.023), while increased Gal-7 promoter methylation was correlated with advanced clinical stage, poor tumor differentiation and regional lymph node metastasis (P<0.05). There was no association between patient age and Gal-7 promoter methylation. Together, these results suggested that Gal-7 has a negative impact in patients with VSCC, with malignant potential correlating with Gal-7 promoter methylation.
[High level expression, purification and cytotoxicity of IL-10(18-57)-PE40]. (2006)

The objective of the experiment is to explore the purification and production of immunotoxin. The chimeric toxin, which is composed of 40 peptides of interleukin 10 (from amino acids 18 to 57) fused to a mutant form of Pseudomonas extoxin (PE) devoid of its native cell recognition domain. Two kinds of prokaryotic expression vector containing the chimeric toxin IL-10(18-57)-PE40 were constructed respectively. After induction of IPTG for 3 hours, IL-10(18-57)-PE40 was expressed highly in cytoplasmic fraction in Rosettablue(DE3), and was directed to periplasmic space as soluble form in E. coli BL21(DE3)pLysS . Western -blotting showed that the expressed protein could react with the specific rabbit sera against LHRH-PE40. With the application of salting out of (NH4)2SO4, hydrophobic interaction chromatography, Cu-affinity chromatography and anion exchange chromatography, the purity of IL-10(18-57)-PE40 was about 96%. The cytotoxicity assay, Cell-ELISA and fluorescent antibody test support the hypothesis that IL-10(18-57) based ligand-mediated cytotoxicity can serve to target cytotoxic agents in vitro.
Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity (2017)

Zika virus (ZIKV) is spreading rapidly into regions around the world where other flaviviruses, such as dengue virus (DENV) and West Nile virus (WNV), are endemic. Antibody-dependent enhancement has been implicated in more severe forms of flavivirus disease, but whether this also applies to ZIKV infection is unclear. Using convalescent plasma from DENV- and WNV-infected individuals, we found substantial enhancement of ZIKV infection in vitro that was mediated through immunoglobulin G engagement of Fcγ receptors. Administration of DENV- or WNV-convalescent plasma into ZIKV-susceptible mice resulted in increased morbidity-including fever, viremia, and viral loads in spinal cord and testes-and increased mortality. Antibody-dependent enhancement may explain the severe disease manifestations associated with recent ZIKV outbreaks and highlights the need to exert great caution when designing flavivirus vaccines.
Novel Potential Antimigraine Compounds: Carotid and Systemic Haemodynamic Effects in a Porcine Model of Migraine (2003)

The term migraine stems from hemicrania, describing a periodic disorder consisting of\nparoxysmal unilateral headache, accompanied by nausea, vomiting, photophobia and/or\nphonophobia. Hemicrania was later changed to Latin words - hemigranea and migranea;\neventually the French cognate, migraine, gained acceptance in the eighteenth century and has\nprevailed ever since. A working definition of migraine is benign recurring headache and/or\nneurological dysfunction usually attended by pain-free interludes and often provoked by\nstereotyped stimuli (1). Migraine may be triggered by certain factors (red wine, menses, hunger,\nlack of sleep, glare, perfumes, periods of let down) and relieved by others (sleep, pregnancy).\nPremonitory symptoms occur hours to a day or two before a migraine attack with or without\naura. Migraine is more common in females, with a hereditary predisposition towards attacks and\nthe cranial circulatory phenomenon appears to be secondary to a primary central nervous system\n(CNS) disorder.\nThe Headache Classification Committee of the International Headache Society (IHS)\npublished the classification and diagnostic criteria for headache disorders in 1988 (Table 1.1) (2).\nThe terms “common migraine” and “classical migraine” have been replaced by “migraine\nwithout aura” and “migraine with aura”, respectively. These operational criteria have been\nvalidated by different approaches and have enabled us to distinguish different headache entities\nin a reliable manner (3-6). In recent years, the IHS criteria have been used world-wide in several\nmulticentre double-blind drug trials, which have shown a reasonably consistent response rate to\ntriptans (7), reflecting a consensus in the defined migraine group. In a recent MAZE survey, the\nMigraine Disability Assessment Scale (MIDAS) questionnaire has been used to assess the impact\nof migraine on work, home and social lives. MIDAS scores confirmed the debilitating effect of\nmigraine; &gt;50% of respondents had a MIDAS grade of III or IV, indicating moderate or severe\ndisability. Less than one-third of patients reported that their current medication was consistently\neffective and only 36% were 'very satisfied' with their current therapy (8). These results show\nthat migraine patients world-wide are still not receiving adequate treatment and a significant\nunmet need in migraine care still remains.