gebhart/patrepeval huggingface dataset:
Alpha-tocopheryl polyethylene glycol succinate-emulsified poly(lactic-co-glycolic acid) nanoparticles for reversal of multidrug resistancein vitro (2012)

Multidrug resistance (MDR) is one of the factors in the failure of anticancer chemotherapy. In order to enhance the anticancer effect of P-glycoprotein (P-gp) substrates, inhibition of the P-gp efflux pump on MDR cells is a good tactic. We designed novel multifunctional drug-loaded alpha-tocopheryl polyethylene glycol succinate (TPGS)/poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPGS/PLGA/SN-38 NPs; SN-38 is 7-ethyl-10-hydroxy-camptothecin), with TPGS-emulsified PLGA NPs as the carrier and modulator of the P-gp efflux pump and SN-38 as the model drug. TPGS/PLGA/SN-38 NPs were prepared using a modified solvent extraction/evaporation method. Physicochemical characterizations of TPGS/PLGA/SN-38 NPs were in conformity with the principle of nano-drug delivery systems (nDDSs), including a diameter of about 200 nm, excellent spherical particles with a smooth surface, narrow size distribution, appropriate surface charge, and successful drug-loading into the NPs. The cytotoxicity of TPGS/PLGA/SN-38 NPs to MDR cells was increased by 3.56 times compared with that of free SN-38. Based on an intracellular accumulation study relative to the time-dependent uptake and efflux inhibition, we suggest novel mechanisms of MDR reversal of TPGS/PLGA NPs. Firstly, TPGS/PLGA/SN-38 NPs improved the uptake of the loaded drug by clathrin-mediated endocytosis in the form of unbroken NPs. Simultaneously, intracellular NPs escaped the recognition of P-gp by MDR cells. After SN-38 was released from TPGS/PLGA/SN-38 NPs in MDR cells, TPGS or/and PLGA may modulate the efflux microenvironment of the P-gp pump, such as mitochondria and the P-gp domain with an ATP-binding site. Finally, the controlled-release drug entered the nucleus of the MDR cell to induce cytotoxicity. The present study showed that TPGS-emulsified PLGA NPs could be functional carriers in nDDS for anticancer drugs that are also P-gp substrates. More importantly, to enhance the therapeutic effect of P-gp substrates, this work might provide a new insight into the design of pharmacologically inactive excipients that can serve as P-gp modulators instead of drugs that are P-gp inhibitors.
PLGA microspheres containing plasmid DNA: Preservation of supercoiled DNA via cryopreparation and carbohydrate stabilization (1999)

Biodegradable microspheres containing plasmid DNA have potential uses as mediators of transfection in cells, particularly phagocytic cells such as macrophages. However, the hydrophilic nature and the structural instability of supercoiled DNA preclude its facile encapsulation in polymer matrixes such as poly(d, l-lactic-co-glycolic acid) (PLGA) by traditional methods. We initially studied the microencapsulation of plasmid DNA using the established water-in-oil-in-water double-emulsion solvent-evaporation method and found that (1) the encapsulation efficiency was low (about 20%), (2) the microencapsulation procedure nicked (degraded) the supercoiled DNA, and (3) lyophilization of the microsphere also nicked the DNA. We have therefore designed a new microsphere preparation method (called cryopreparation) to specifically address these concerns. Using the cryopreparation method, the aqueous phase of the primary emulsion containing the plasmid DNA is frozen and then subjected to homogenization. Because there is no shear stress inside a solid, we hypothesized that freezing the aqueous phase of the primary emulsion would help to preserve the supercoiled plasmid DNA during formation of the secondary emulsion. We also hypothesized that the formation of crystals from buffers within the primary emulsion was a causative factor for nicking during freezing or lyophilization, and that disruption of the crystal formation by the addition of saccharides into the primary emulsion would improve the supercoiled-DNA content of the spheres. Our results support the two hypotheses. Not only was the supercoiled-DNA content increased from 39% to over 85%, but the encapsulation efficiency was also elevated from 23% to over 85%.
Functional role of the antigen recognized by an antiplatelet antibody specific for a putative collagen receptor in platelet-collagen interaction. (1993)

Collagen, a major component of blood vessels, mediates primary hemostasis brought about by platelets. The mechanism underlying platelet-collagen interaction is highly complicated and to date various molecules have been suggested to be platelet collagen receptors. We suggest that a platelet membrane protein with a molecular weight of 62 kDa in the reducing condition (P62) immunoprecipitated by the antibody of a patient with idiopathic thrombocytopenic purpura could be a platelet collagen receptor. The antibody was also primarily immunoreactive with P62 on immunoblotting. The patient's platelets, which were deficient in P62 and totally lacked collagen-induced platelet aggregation, showed normal platelet adhesion to collagen in the presence of Mg2+. However, the Fabs of the antibody, which completely abolished collagen-induced normal platelet aggregation, also had inhibitory effects on normal platelet adhesion to collagen. These results indicate that of the antigens recognized by this antibody, P62 could play an important role in platelet-collagen interaction mediating aggregation, and that multiple membrane molecules, including P62, may participate in platelet adhesion to collagen.
Study of Holographic Waveguide Display System (2014)

We study the holographic waveguide display system to solve the problems, such as the chromatic dispersion, the non-uniform output intensity, and the low diffraction efficiency. Several examples and the prototype are presented.
Role of keratinocytes in healing of chronic wounds. (2008)

Keratinocytes are the major cellular component of epidermis, and they have several critical roles in the wound healing process. They are involved in the intricate mechanisms of initiation, maintenance, and completion of wound healing. The properties of keratinocytes vary depending upon their location and circumstances within chronic wounds. Keratinocytes at the non-healing edges of chronic wounds differ from normal, healthy keratinocytes. The cross-talk between healthy keratinocytes and other cell types participating in wound healing is critical for successful wound closure. This discovery provides the biological foundation for debridement: Removing "bad" cells from a quiescent wound edge and exposing or even replacing them with "healthy" cells with a high regenerative potential can enhance epithelialization and healing of chronic wounds. This paper will review the biological and pathological properties of keratinocytes as they relate to wound healing, and the ways in which they may provide highly efficacious therapy for patients with chronic wounds.
Growth of Millimeter-Long and Horizontally Aligned Single-Walled Carbon Nanotubes on Flat Substrates (2003)

Millimeter-long and well-aligned single-walled carbon nanotubes (SWNTs) have been produced on silica/silicon surfaces using the carbon monoxide chemical vapor deposition (CO-CVD) method. The orientation of the nanotube arrays can be well-controlled by the gas flow during the growth. The majority of the orientated SWNTs are straight and individual. The length of the nanotubes can be >2 mm for a 10 min growth. Furthermore, multidimensional crossed-networks of SWNT can be easily generated by multistep processes. These results present a great opportunity in the controllable production of organized SWNT arrays for large-scale carbon nanotube-based nanodevice fabrication.
Synthesis of N‐(2‐chloro‐3,4‐dimethoxybenzylideneamino)guanidinium acetate [α‐14C] (2002)

Abstract 14 C‐Labelled N ‐(2‐chloro‐3,4‐dimethoxybenzylideneamino)guanidinium acetate has been synthesized as a part of a four‐step procedure which involved decarboxylation of 2‐chloro‐3,4‐dimethoxybenzoic acid by Pb(OAc) 4 to give 2‐chloro‐3,4‐dimethoxy‐1‐iodobenzene, followed by a selective lithiation at the iodine position and electrophilic substitution with N , N ‐dimethylformamide [ α ‐ 14 C] and final reaction with aminoguanidine bicarbonate. The specific activity was 59 mCi/mmol and the overall yield 49%. Copyright © 2002 John Wiley &amp; Sons, Ltd.
Plasma levels of immunoreactive erythropoietin after acute blood loss in man (1982)

Plasma levels of immunoreactive erythropoietin (Ep) were measured after acute blood loss (50, 75, 200 and 450 ml) in man in order to determine the volume of blood loss required to trigger an Ep response as well as to define the reticulocyte response. There was a highly significant (P less than 0.01) linear increase in reticulocyte count after 200 and 450 ml of blood loss. Analysis of trends also showed a highly significant (P less than 0.01) linear response of haematocrit and Ep after a 450 ml blood loss. The reticulocyte count increases were not dependent on a prior increase in Ep level indicating that at least two mechanisms are operative in restoring the red cell mass to normal after blood loss.
Identification of substrate specificity determinants for the cell cycle-regulated NIMA protein kinase. (1994)

NIMA is a cell cycle-regulated protein kinase required for the G2/M transition in the filamentous fungus Aspergillus nidulans. Previous biochemical characterization of the recombinant enzyme indicated that NIMA is a protein serine/threonine specific kinase with beta-casein being the best substrate from the many proteins and peptides tested (Lu, K.P., Osmani, S.A., and Means, A.R. (1993) J. Biol. Chem. 268, 8769-8776). However, substrate specificity or physiologically relevant substrates for NIMA remained unknown. In search for a peptide substrate for this enzyme, we screened an assembled library of synthetic peptides that each contained a phosphorylation site for a known protein kinase and found an excellent peptide substrate for NIMA, phospholemman 42-72 (PLM(42-72)). NIMA kinase phosphorylated PLM(42-72) uniquely and stoichiometrically on Ser63 with a Vmax of 1.4 mumol/min/mg and apparent Km of 20.0 microM. These kinetic constants were about 10-fold higher and 3-fold lower than those for beta-casein, respectively. A detailed analysis of substrate specificity determinants using synthetic peptide analogs of PLM(42-72) indicated that Phe-Arg-Xaa-Ser/Thr represents the optimal primary sequence for NIMA kinase phosphorylation. Replacement of the Arg at P-2 with Ala resulted in a 6-fold increase in Km and 2-fold decrease in Vmax, while substitution of the Phe at P-3 with Ala abolished NIMA phosphorylation. These results reveal the unique nature of substrate recognition by the NIMA kinase and should prove valuable in the search for biologically relevant NIMA substrates.
Two TIR:NB:LRR genes are required to specify resistance to Peronospora parasitica isolate Cala2 in Arabidopsis (2004)

Resistance responses that plants deploy in defence against pathogens are often triggered following a recognition event mediated by resistance (R) genes. The encoded R proteins usually contain a nucleotide-binding site (NB) and a leucine-rich repeat (LRR) domain. They are further classified into those that contain an N-terminal coiled coil (CC) motif or a Toll interleukin receptor (TIR) domain. Such R genes, when transferred into a susceptible plant of the same or closely related species, usually impart full resistance capability. We have used map-based cloning and mutation analysis to study the recognition of Peronospora parasitica (RPP)2 (At) locus in Arabidopsis accession Columbia (Col-0), which is a determinant of specific recognition of P. parasitica (At) isolate Cala2. Genetic mapping located RPP2 to a 200-kb interval on chromosome 4, which contained four adjacent TIR:NB:LRR genes. Mutational analysis revealed three classes of genes involved in specifying resistance to Cala2. One class, which resulted in pleiotropic effects on resistance to other P. parasitica (At) isolates, was unlinked to the RPP2 locus; this class included AtSGT1b. The other two classes were mapped within the interval and were specific to Cala2 resistance. Representatives of each of these classes were sequenced, and mutations were found in one or the other of two (RPP2A and RPP2B) of the four TIR:NB:LRR genes. RPP2A and RPP2B complemented their specific mutations, but failed to impart resistance when present alone, and it is concluded that both genes are essential determinants for isolate-specific recognition of Cala2. RPP2A has an unusual structure with a short LRR domain at the C-terminus, preceded by two potential but incomplete TIR:NB domains. In addition, the RPP2A LRR domain lacks conserved motifs found in all but three other TIR:NB:LRR class proteins. In contrast, RPP2B has a complete TIR:NB:LRR structure. It is concluded that RPP2A and RPP2B cooperate to specify Cala2 resistance by providing recognition or signalling functions lacked by either partner protein.
MECHANISMS IN ENDOCRINOLOGY: Biological role, clinical significance, and therapeutic possibilities of the recently discovered metabolic hormone fibroblastic growth factor 21 (2012)

Fibroblast growth factor 21 (FGF21), a 181 amino acid circulating protein, is a member of the FGF superfamily, with relevant metabolic actions. It acts through the interaction with specific FGF receptors and a cofactor called β-Klotho, whose expression is predominantly detected in metabolically active organs. FGF21 stimulates glucose uptake in adipocytes via the induction of glucose transporter-1. This action is additive and independent of insulin. β-Cell function and survival are preserved, and glucagon secretion is reduced by this protein, thus decreasing hepatic glucose production and improving insulin sensitivity. Lipid profile has been shown to be improved by FGF21 in several animal models. FGF21 increases energy expenditure in rodents and induces weight loss in diabetic nonhuman primates. It also exerts favorable effects on hepatic steatosis and reduces tissue lipid content in rodents. Adaptive metabolic responses to fasting, including stimulation of ketogenesis and fatty acid oxidation, seem to be partially mediated by FGF21. In humans, serum FGF21 concentrations have been found elevated in insulin-resistant states, such as impaired glucose tolerance and type 2 diabetes. FGF21 levels are correlated with hepatic insulin resistance index, fasting blood glucose, HbA1c, and blood glucose after an oral glucose tolerance test. A relationship between FGF21 levels and long-term diabetic complications, such as nephropathy and carotid atheromatosis, has been reported. FGF21 levels decreased in diabetic patients after starting therapy with insulin or oral agents. Increased FGF21 serum levels have also been found to be associated with obesity. In children, it is correlated with BMI and leptin levels, whereas in adults, FGF21 levels are mainly related to several components of the metabolic syndrome. Serum FGF21 levels have been found to be elevated in patients with ischemic heart disease. In patients with renal disease, FGF21 levels exhibited a progressive increase as renal function deteriorates. Circulating FGF21 levels seem to be related to insulin resistance and inflammation in dialysis patients. In summary, FGF21 is a recently identified hormone with antihyperglycemic, antihyperlipidemic, and thermogenic properties. Direct or indirect potentiation of its effects might be a potential therapeutic target in insulin-resistant states.
"My Country! 'Tis of Thee, Strong hold of Slavery": The Musical Rhetoric of the American Antislavery Movement (2010)

My Country! 'Tis of Thee, Strong hold of Slavery: The Musical Rhetoric of the American Antislavery Movement
A 98 mm/sup 2/ 3.3 V 64 Mb flash memory with FN-NOR type 4-level cell (2002)

A 64 Mb flash memory has a multi-level cell and 64-memory-cell parallel programming. 98 mm/sup 2/ die uses 0.4 /spl mu/m CMOS and 4-levels (2b) per cell. 3.3 V operation and 6.3 /spl mu/s/B programming are achieved by using a Fowler-Nordheim (FN) NOR memory cell. Drain-voltage controlled multilevel programming (DCMP) is the key technology for simultaneous multi-level programming in the chip. To implement DCMP, a parallel multi-level verify (PMV) circuit and the compact multi-level sense amplifier (CMS), which enable a 64-memory-cells parallel programming operation (program/program verify), are used.
Psychopathology and Personality Trait in Subgroups of Functional Dyspepsia Based on Rome III Criteria (2009)

OBJECTIVES: Functional dyspepsia is a heterogeneous symptom complex that may be subdivided into postprandial distress syndrome and epigastric pain syndrome. We aimed to investigate differences among these subgroups in psychopathological factors and personality traits. METHODS: We enrolled 187 consecutive outpatients (72.2% female patients, mean age 42.6 years) with functional dyspepsia based on the Rome III criteria. Patients were interviewed and evaluated by the Brief Symptom Rating Scale and the short-form Maudsley personality inventory for severity of psychopathology and personality traits. Multiple linear regression models were built for each psychopathological dimension and personality trait to assess the independent association with each subclass diagnosis of functional dyspepsia. RESULTS: There was an overlap (n=64, 34.2%) between the patients diagnosed with epigastric pain syndrome (n=157, 84.0%) and those with postprandial distress syndrome (n=94, 50.3%). Patients with symptoms compatible with both syndromes were psychopathologically more severe than either subgroup without overlapping. Multiple linear regression analysis demonstrated that the diagnosis of postprandial distress syndrome was independently associated with higher scores in overall psychopathological stress, and specifically in somatization (P=0.034), depression (P=0.028), phobia (P=0.044), and additional symptoms (P<0.001). However, epigastric pain syndrome was not associated with psychopathology. Postprandial distress was univariately associated with neuroticism, but the association was insignificant in the multivariate analysis (P=0.136). CONCLUSIONS: The Rome III subgroups of functional dyspepsia significantly overlap. Patients fulfilling criteria for both subgroups had symptoms that were psychopathologically more severe than those of patients without overlapping. Diagnosis of postprandial distress syndrome, but not epigastric pain syndrome, is independently associated with psychopathological factors. Am J Gastroenterol 2009; 104:2534-2542; doi:10.1038/ajg.2009.328; published online 16 June 2009
Hemodynamic forces are complex regulators of endothelial gene expression (1995)

Vascular endothelial cells, by virtue of their unique anatomical position, are constantly exposed to the fluid mechanical forces generated by flowing blood. In vitro studies with model flow systems have demonstrated that wall shear stresses can modulate various aspects of endothelial structure and function. Certain of these effects appear to result from the regulation of expression of endothelial genes at the transcriptional level. Recent molecular biological studies have defined a "shear stress response element" (SSRE) in the promoter of the human platelet-derived growth factor (PDGF)-B chain gene that interacts with DNA binding proteins in the nuclei of shear-stressed endothelial cells to up-regulate transcriptional activity. Insertion of this element into reporter genes also renders them shear-inducible. Further characterization of this and other positive (and negative) shear-responsive genetic regulatory elements, as well as their transactivating factors, should enhance our understanding of vascular endothelium as an integrator of humoral and biomechanical stimuli in health and disease.
A novel assay for screening inhibitors targeting HIV-1 integrase dimerization based on Ni-NTA magnetic agarose beads (2016)

Human immunodeficiency virus (HIV)-1 integrase (IN), which mediates integration of viral cDNA into the cellular chromosome, is a validated antiviral drug target. Three IN inhibitors, raltegravir, elvitegravir and dolutegravir, have been clinically approved since 2008. However, drug resistance have emerged in infected patients receiving treatment using these drugs which share the same mechanism of action and have a low genetic barrier for resistance. Therefore, there is an urgent need to develop drugs with novel mechanism. IN requires a precise and dynamic equilibrium between several oligomeric species for its activities. The modulation of the process which is termed as IN oligomerization, presents an interesting allosteric target for drug development. In this research, we developed a magnetic beads based approach to assay the IN dimerization. Then, using the assay we screened a library of 1000 Food and Drug Administration (FDA)-approved drugs for IN dimerization inhibitors and identified dexlansoprazole as a potential IN dimerization inhibitor. In conclusion, the assay presented here has been proven to be sensitive and specific for the detection of IN dimerization as well as for the identification of antiviral drugs targeting IN dimerization. Moreover, a FDA-approved proton-pump inhibitors, dexlansoprazole, was identified as a potential inhibitor for IN dimerization.
ROR1, an embryonic protein with an emerging role in cancer biology (2014)

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the ROR family consisting of ROR1 and ROR2. RORs contain two distinct extracellular cysteine-rich domains and one transmembrane domain. Within the intracellular portion, ROR1 possesses a tyrosine kinase domain, two serine/threonine-rich domains and a proline-rich domain. RORs have been studied in the context of embryonic patterning and neurogenesis through a variety of homologs. These physiologic functions are dichotomous based on the requirement of the kinase domain. A growing literature has established ROR1 as a marker for cancer, such as in CLL and other blood malignancies. In addition, ROR1 is critically involved in progression of a number of blood and solid malignancies. ROR1 has been shown to inhibit apoptosis, potentiate EGFR signaling, and induce epithelial-mesenchymal transition (EMT). Importantly, ROR1 is only detectable in embryonic tissue and generally absent in adult tissue, making the protein an ideal drug target for cancer therapy.
Transvaginal Ultrasound for Identifying Endometrial Abnormality (1991)

Transvaginal ultrasound was used preoperatively to evaluate the endometrium in 96 patients referred for dilatation and curettage. The sonographic display was correlated to the histopathologic diagnosis. In 45 patients with postmenopausal bleeding, 4 patients had adenocarcinoma of the endometrium. All were identified by ultrasound. None of the 22 patients with a normal sonographic appearance had an abnormal histopathologic diagnosis. An endometrial thickness (single layer) cut-off point of greater than or equal to 4 mm precluded any missed malignancies but halves the number of dilatations and curettages in this postmenopausal group. The sensitivity of ultrasound in diagnosing endometrial pathology was 100% and the specificity was 61%. The positive and negative predictive values were 39% and 100% respectively. In 51 premenopausal women there was good agreement between histology and ultrasound. In this group a cut-off point of greater than or equal to 8 mm was used. The sensitivity in diagnosing endometrial pathology was 67% and the specificity 75%. The positive and negative predictive values were 14% and 97%. With further experience, transvaginal ultrasound might be used in clinical routine for diagnosing endometrial pathology.
Combining Textual Entailment and Argumentation Theory for Supporting Online Debates Interactions. (2012)

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