gebhart/patrepeval huggingface dataset:
Varying quality of fish oil capsules: fatty acids and tocopherol. (2011)

The tested samples of oil capsules showed large variation in quality with respect to long-chain n-3 polyunsaturated fatty acids and tocopherols. The low levels of malondialdehyde indicated a successful oxidation protection strategy.
Activation and inhibition of G protein-coupled receptors by cell-penetrating membrane-tethered peptides (2002)

Classical ligands bind to the extracellular surface of their cognate receptors and activate signaling pathways without crossing the plasma membrane barrier. We selectively targeted the intracellular receptor-G protein interface by using cell-penetrating membrane-tethered peptides. Attachment of a palmitate group to peptides derived from the third intracellular loop of protease-activated receptors-1 and -2 and melanocortin-4 receptors yields agonists and/or antagonists of receptor-G protein signaling. These lipidated peptides--which we have termed pepducins--require the presence of their cognate receptor for activity and are highly selective for receptor type. Mutational analysis of both intact receptor and pepducins demonstrates that the cell-penetrating agonists do not activate G proteins by the same mechanism as the intact receptor third intracellular loop but instead require the C-tail of the receptor. Construction of such peptide-lipid conjugates constitutes a new molecular strategy for the development of therapeutics targeted to the receptor-effector interface.
Solution Cross-Linked Natural Rubber (NR)/Clay Aerogel Composites (2011)

Aerogels are structural materials with ultralow bulk densities (often less than 0.1 g cm−3), which stand out as good candidates for a variety of applications. In the present study, natural rubber (NR)/clay aerogel composites were produced by freeze-drying of the aqueous aerogel precursor suspensions, followed by solution cross-linking of the aerogel samples in benzene using sulfur monochloride (S2Cl2) as a cross-linking agent. The influences of cross-linking conditions, i.e., cross-linker concentration and reaction temperature, as well as polymer loading on the aerogel structure and properties were investigated. 1% (v/v) of S2Cl2 and reaction temperature of −18 °C were found to be the optimum conditions for producing a strong and tough rubber composite; the 2.5 wt % NR aerogel, for example, after being cross-linked, exhibited a compressive modulus of 1.8 MPa, 26 times higher than that of the neat control. These favorable mechanical properties are attributed to the high local concentration of rubber and S2Cl2 in the freeze-dried structures, giving rise to the high cross-linking efficiency. Increasing the rubber concentration led to a substantial increase in the mechanical strength, in accord with the changes in microstructure and degree of cross-linking. The swelling capacity of the NR aerogels decreased with either increasing the cross-linker concentration or decreasing the weight fraction of rubber. Cross-linking of the rubber aerogels brought about increased thermal stability, consistent with restricted thermal motion of NR chains.
Role of Neural Cell Adhesion Molecule and Polysialic Acid in Mouse Circadian Clock Function (1997)

The suprachiasmatic nuclei (SCN) express the highly polysialylated form of the neural cell adhesion molecule (NCAM) that has been proposed to promote plasticity in the adult brain. To investigate a role for NCAM in SCN circadian clock function, we examined the daily locomotor rhythm of mice homozygous for a mutation, Ncamtm1Cwr, which results in deletion of the NCAM-180 isoform that in brain carries polysialic acid (PSA). Mutant mice entrained well to a 12 hr light/dark cycle but exhibited a significantly shortened free-running period and longer activity duration under constant darkness (DD) than did wild-type mice. By the third week of DD treatment, circadian rhythmicity in the mutant was abolished. Immunocytochemical analyses of the mutant SCN revealed an abnormal number and distribution of vasoactive intestinal polypeptide-producing neurons, suggesting a developmental effect of the mutant phenotype; however, a direct physiological effect of the mutation on clock function was indicated by the fact that removal of PSA from adult wild-type SCN by microinjection of endoneuraminidase shortened the free-running period to a similar extent as in the mutant. Together, these data indicate critical roles for NCAM and PSA in the development and physiology of the mammalian SCN circadian clock.
Homology of yeast mitochondrial leucyl-tRNA synthetase and isoleucyl- and methionyl-tRNA synthetases of Escherichia coli. (1988)

Respiratory deficient mutants of Saccharomyces cerevisiae previously assigned to complementation group G59 are pleiotropically deficient in respiratory chain components and in mitochondrial ATPase. This phenotype has been shown to be a consequence of mutations in a nuclear gene coding for mitochondrial leucyl-tRNA synthetase. The structural gene (MSL1) coding for the mitochondrial enzyme has been cloned by transformation of two different G59 mutants with genomic libraries of wild type yeast nuclear DNA. The cloned gene has been sequenced and shown to code for a protein of 894 residues with a molecular weight of 101,936. The amino-terminal sequence (30-40 residues) has a large percentage of basic and hydroxylated residues suggestive of a mitochondrial import signal. The cloned MSL1 gene was used to construct a strain in which 1 kb of the coding sequence was deleted and substituted with the yeast LEU2 gene. Mitochondrial extracts obtained from the mutant carrying the disrupted MSL1::LEU2 allele did not catalyze acylation of mitochondrial leucyl-tRNA even though other tRNAs were normally charged. These results confirmed the correct identification of MSL1 as the structural gene for mitochondrial leucyl-tRNA synthetase. Mutations in MSL1 affect the ability of yeast to grow on nonfermentable substrates but are not lethal indicating that the cytoplasmic leucyl-tRNA synthetase is encoded by a different gene. The primary sequence of yeast mitochondrial leucyl-tRNA synthetase has been compared to other bacterial and eukaryotic synthetases. Significant homology has been found between the yeast enzyme and the methionyl- and isoleucyl-tRNA synthetases of Escherichia coli. The most striking primary sequence homology occurs in the amino-terminal regions of the three proteins encompassing some 150 residues. Several smaller domains in the more internal regions of the polypeptide chains, however, also exhibit homology. These observations have been interpreted to indicate that the three synthetases may represent a related subset of enzymes originating from a common ancestral gene.
Self-Assembled Micronanoplexes for Improved Biolistic Delivery of Nucleic Acids (2009)

A new method for biolistic delivery of nucleic acids using a combination of cationic micro- and nanoparticles is reported. The new method is simpler to perform than the conventional calcium/spermidine-based formulations and shows 11-fold improved nucleic acid binding capacity and dose-dependent performance both for in vitro and in vivo applications relative to either the conventional preparation or our recently reported direct cationic microparticle method. These features may enable higher throughput gene delivery and genetic immunization programs and open new venues for the biolistic delivery method.
Context-aware discriminative phrase selection for statistical machine translation (2007)

In this work we revise the application of discriminative learning to the problem of phrase selection in Statistical Machine Translation. Inspired by common techniques used in Word Sense Disambiguation, we train classifiers based on local context to predict possible phrase translations. Our work extends that of Vickrey et al. (2005) in two main aspects. First, we move from word translation to phrase translation. Second, we move from the 'blank-filling' task to the 'full translation' task. We report results on a set of highly frequent source phrases, obtaining a significant improvement, specially with respect to adequacy, according to a rigorous process of manual evaluation.
Induction of indoleamine 2,3-dioxygenase: a mechanism of the antitumor activity of interferon gamma. (1988)

The antiproliferative effects of interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma) were found to be cell-dependent. Among the human cell lines examined, IFN-gamma had a greater antiproliferative effect against cell lines that exhibited induction of indoleamine 2,3-dioxygenase, such as the KB oral carcinoma or WiDr colon adenocarcinoma, than against those that lacked the enzyme activity, such as the SW480 colon adenocarcinoma or NCI-H128 small-cell lung carcinoma. Induction of this dioxygenase showed a clear temporal relationship with increased metabolism of L-tryptophan and the depletion of this amino acid in the culture medium. While 70-80% of L-tryptophan remained in the medium of IFN-alpha- or vehicle-treated cells, virtually all of this amino acid was depleted in the medium of the IFN-gamma-treated group following 2-3 days of culture. Supplementing the growth medium with additional L-tryptophan reversed the antiproliferative effect of IFN-gamma against KB cells in a dose- and time-dependent manner. The antiproliferative effects of IFN-alpha and IFN-gamma on SW480 and NCI-H128 cells, which are independent of the dioxygenase activity, and the inability of added L-tryptophan to reverse the effects of IFN-gamma in WiDr cells suggest multiple mechanisms of action of the IFNs. The data show that the antiproliferative effect of IFN-gamma through induction of indoleamine 2,3-dioxygenase, with a consequent L-tryptophan deprivation, is an effective means of regulating cell growth.
Identification of Fn14/TWEAK receptor as a potential therapeutic target in esophageal adenocarcinoma (2007)

Given the poor survival rate and efficacy of current therapy for esophageal adenocarcinoma (EAC), there is a need to identify and develop new therapeutic targets for treatment. Microarray analysis (Affymetrix U133A GeneChips, Robust Multi-Chip Analysis) was used to expression profile 11 normal squamous and 18 Barrett's esophagus biopsies, 7 surgically resected EACs and 3 EAC cell lines. Two hundred transcripts representing potential therapeutic targets were identified using the following criteria: significant overexpression in EAC by analysis of variance (p = 0.05, Benjamini Hochberg false discovery rate); 3-fold increase in EAC relative to normal and Barrett's esophagus and expression in at least 2 of the 3 EAC cell lines. From the list of potential targets we selected TNFRSF12A/Fn14/TWEAK receptor, a tumor necrosis factor super-family receptor, for further validation based on its reported role in tumor cell survival and potential as a target for therapy. Fn14 protein expression was confirmed in SEG-1 and BIC-1 cell lines, but Fn14 was not found to affect tumor cell survival after exposure to chemotherapeutics as expected. Instead, a novel role in EAC was discovered in transwell assays, in which modulating Fn14 expression affected tumor cell invasion. Fn14's potential as a therapeutic target was further supported by immunohistochemistry on a tissue microarray of patient samples that showed that Fn14 protein expression increased with disease progression in EAC.
The Use of 2 Bioabsorbable Barrier Membranes in the Treatment of Interproximal Intrabony Periodontal Defects (1999)

Background: The use of barrier membranes in the treatment of periodontal defects is well documented. There has been an increase in the use of bioabsorbable materials which do not require a second surgical procedure for removal. However, there are little data evaluating the efficacy of bioabsorbable membranes in the treatment of intrabony defects. The purpose of this investigation was to evaluate the regenerative potential of 2 bioabsorbable barrier membranes without the use of grafting materials in the treatment of interdental intrabony defects. Methods: Twenty‐three 2‐ or 3‐walled intrabony defects were treated in 19 patients with a mean age of 50.4 years. All had completed nonsurgical treatment and a period of supportive periodontal therapy. The sites were randomly chosen to receive a barrier membrane composed of type I bovine collagen (11) or a copolymer of polylactic acid (PGA/PLA;12). A pressure sensitive disc probe was used to evaluate the following criteria at baseline and re‐entry: 1) occlusal surface to the apical depth of probe penetration (OS‐DP); 2) occlusal surface to the gingival margin (OS‐GM); 3) occlusal surface to the alveolar crest (OSAC); and 4) occlusal surface to the base of the osseous defect (OS‐BD). Full thickness mucoperiosteal flaps were reflected to expose the surgical sites. The defects were debrided of the granulomatous tissue, the root surfaces instrumented and conditioned with 4 one‐minute applications of 50 mg/ml of tetracycline. The barrier membranes were adapted to cover the defects and the flaps replaced. The postsurgical healing was uneventful and similar in both treatment modalities. Results: Twenty‐three sites were surgically re‐entered 6 months from the time of the initial surgery. The deepest probe depth for each site was used for statistical analysis. There was a mean relative attachment gain of 2.58 ± 1.90 mm for the collagen, and 2.77 ± 2.13 mm for the copolymer. There was a decrease in probing depth of 3.27 ± 1.91 mm and 0.69 ± 1.35 mm of recession for the collagen. The PGA/PLA copolymer had 3.55 ± 2.47 mm reduction in probe depth and 0.78 ± 1.14 mm of recession. Conclusions: The data indicated the bioabsorbable collagen and copolymer membranes resulted in comparable results. A larger sample size would be necessary to determine if one membrane was superior to the other. J Periodontol 1999;70:510‐517 .
Development of a perfusion fed bioreactor for embryonic stem cell‐derived cardiomyocyte generation: Oxygen‐mediated enhancement of cardiomyocyte output (2005)

Cell transplantation is emerging as a promising new approach to replace scarred, nonfunctional myocardium in a diseased heart. At present, however, generating the numbers of donor cardiomyocytes required to develop and test animal models is a major limitation. Embryonic stem (ES) cells may be a promising source for therapeutic applications, potentially providing sufficient numbers of functionally relevant cells for transplantation into a variety of organs. We developed a single-step bioprocess for ES cell-derived cardiomyocyte production that enables both medium perfusion and direct monitoring and control of dissolved oxygen. Implementation of the bioprocess required combining methods to prevent ES cell aggregation (hydrogel encapsulation) and to purify for cardiomyocytes from the heterogeneous cell populations (genetic selection), with medium perfusion in a controlled bioreactor environment. We used this bioprocess to investigate the effects of oxygen on cardiomyocyte generation. Parallel vessels (250 mL culture volume) were run under normoxic (20% oxygen tension) or hypoxic (4% oxygen tension) conditions. After 14 days of differentiation (including 5 days of selection), the cardiomyocyte yield per input ES cell achieved in hypoxic vessels was 3.77 +/- 0.13, higher than has previously been reported. We have developed a bioprocess that improves the efficiency of ES cell-derived cardiomyocyte production, and allows the investigation of bioprocess parameters on ES cell-derived cardiomyogenesis. Using this system we have demonstrated that medium oxygen tension is a culture parameter that can be manipulated to improve cardiomyocyte yield.
Erythropoietin receptor mRNA expression in human endothelial cells. (1994)

A previous report demonstrated that endothelial cells have erythropoietin receptors and respond to this hormone with enhanced proliferation. The present study demonstrates the existence of mRNA for erythropoietin receptor in human umbilical vein endothelial cells. We have reverse transcribed mRNA of endothelial cells and then used different PCR primers to amplify erythropoietin receptor target cDNA between exons 5 and 6 as well as 3-5 in addition to an internal standard DNA fragment. Correspondence of size as well as location of restriction endonuclease scission (Ava II) was used in comparing the amplified fragments of human endothelial cell erythropoietin receptor to those of two human erythroleukemia cell lines, OCIM1 and K562. No alpha- or gamma-globin mRNA was detected in endothelial cells but was readily demonstrable in OCIM1 cells. In addition, to determine whether the expression of human erythropoietin receptor on endothelial cells occurs in vivo, sections of umbilical cord and placenta were immunostained with antibodies against the extracellular portion of the receptor; the results showed strong positive staining of the vascular endothelium.
Vascular injury induces angiotensinogen gene expression in the media and neointima. (1993)

These data are consistent with the hypothesis that balloon injury leads to activation of the vascular renin-angiotensin system, which may participate in the myointimal proliferation.
A single nine-amino acid peptide induces virus-specific, CD8+ human cytotoxic T lymphocyte clones of heterogeneous serotype specificities. (1995)

It is generally accepted that virus-specific CD8+ cytotoxic T lymphocytes (CTLs) recognize nine-amino acid peptides in conjunction with HLA class I molecules. We recently reported that dengue virus-specific CD8+ CTLs of two different serotype specificities, which were established by stimulation with dengue virus, recognize a single nine-amino acid peptide of the nonstructural protein NS3 of dengue virus type 4 (D4V) in an HLA-B35-restricted fashion. To further analyze the relationships between the serotype specificities of T cells and the amino acid sequence of the recognized peptides, we examined the ability of this viral peptide D4.NS3.500-508 (TPEGIIPTL) to stimulate T lymphocytes of an HLA-B35-positive, dengue virus type 4-immune donor. Peptide stimulation of the PBMC generated dengue virus-specific, HLA-B-35-restricted CD8+ CTL clones. These clones lysed dengue virus-infected autologous cells, as well as autologous target cells pulsed with this peptide. Four patterns of dengue virus serotype specificities were demonstrated on target cells infected with dengue-vaccinia recombinant viruses or pulsed with synthetic peptides corresponding to amino acid sequences of four dengue virus serotypes. Two serotype-specific clones recognized only D4V. Three dengue virus subcomplex-specific clones recognized D1V, D3V, and D4V, and one subcomplex-specific clone recognized D2V and D4V. Three dengue virus serotype-cross-reactive clones recognized D1V-D4V. Thus, a single nine-amino acid peptide induces proliferation of a heterogeneous panel of dengue virus-specific CD8+ CTL clones that are all restricted by HLA-B35 but have a variety of serotype specificities. Peptides that contain a single amino acid substitution at each position of D4.NS3.500-508 were recognized differently by the T cell clones. These results indicate that a single epitope can be recognized by multiple CD8+ CTLs that have a variety of serotype specificities, but the manner of recognition by these multiple CTLs is heterogeneous.
Recombinant dna in Filamentous Fungi: Progress and Prospects (1987)

Recombinant DNA technology enables the creation of well-defined alterations in the genetic material of an organism. Methods to manipulate recombinant DNA in the filamentous fungi (a group of microorganisms that includes species of academic as well as commercial interest) have recently been developed. This has been the result of adaptation of procedures successfully employed in the manipulation of other microorganisms. There are a number of similarities in the behavior of recombinant DNA in different fungi, but a number of differences have also been observed between the filamentous and the nonfilamentous fungi. Such differences include the ability to identify DNA replication origins and the host range of expression of fungal genes.
Magnetoresistance and Current-Driven Resistance Change Measurements in NiFe Film With a Nanoconstriction (2006)

A nano fabricated planar point contact (PC) in NiFe film showed a magnetoresistance (MR) ratio of about 18%, and it stabilized at about 12%; with both values being much larger than those for the anisotropic MR (AMR) ratio of the film. The measurements of current-driven resistance change in the PC were also performed in which about 10.5% resistance change was observed. The saturated resistances coincided with the typical values in the MR measurements (MR: 12%). These results inspired correlation between MR and domain wall.
5-Aza-2'-Deoxycytidine Promotes Cytotoxic Effect of CART-Cells on Leukaemia Cells (2014)

Abstract T cells modified to express CD19-specific chimeric antigen receptors (CAR) have shown anti-tumour efficacy in early phase clinical trials in patients with relapsed and refractory B-cell malignancies. In addition to direct cytotoxicity, chemotherapeutic drugs can have an immunomodulatory effect both through enhancing the tumour-specific immune response and increasing the tumour’s susceptibility to immune mediated destruction. Hence, combining immunomodulatory chemotherapy and CAR T-cells is an attractive approach for eliminating tumours, particularly in advanced stages. 5-aza-2'-deoxycytidine (5-AZA) is a hypomethylating agent that induces terminal differentiation, senescence or apoptosis in haematological malignancies. Here, we have explored a CAR-based immunotherapy combined with 5-AZA to maximise the effect of the CAR T-cells against CD19+ B-cell leukaemia. A second generation CAR including CD3zeta and the CD28 co-stimulatory domain was cloned into the PiggyBac-transposon vector and was used to generate CAR19 -T cells. Cord blood -derived mononuclear cells (MNC) were transfected with CAR19-transposon/transposase plasmids and expanded with CD3/28 beads for 2 weeks in the presence of 20ng/ml IL2 and 10ng/ml IL7. CAR19 T-cells efficiently induced cytolysis of CD19+ leukaemia cells in vitro and exhibited anti-tumour activity in vivo in a xenograft mouse model of leukaemia. Pre-treatment with 5-AZA produced greater leukaemia cell cytolysis in vitro and maximised anti-tumour activity of CAR19 T-cells in vivo against xenograft primary leukaemia compared to 5-AZA or CAR19 T-cells alone. In vitro analysis revealed that pre-treatment with 5-AZA up-regulates CD19 expression in leukaemia cells and improves CAR19 T-cell recognition of target cells increasing the formation of effector/ target cell conjugates and target cell cytolysis. Therefore using 5-AZA pre-treatment can be particularly useful for B-cell leukaemias with reduced expression of CD19. We have also demonstrated that pre-treatment of target cells with 5-AZA potentiates the effect of CAR19 T-cells used at low dose or low effector:target (E:T) suggesting that even small numbers of CAR19 T-cells can mediate a potent antitumor effect when combined with 5-AZA pre-treatment of target cells. This is particularly important for patients receiving limited numbers of CAR T-cells or for patients with large leukaemic burden. In addition, we speculate that the enhanced cellular cytotoxicity produced by 5-AZA-conditioning may allow the infusion of decreased numbers of CAR19 T-cells. Disclosures No relevant conflicts of interest to declare.
Reduction of LOX- and LOXL2-mRNA expression in head and neck squamous cell carcinomas. (2003)

These findings support the presumption that LOX is involved in tumor suppressive processes and also of LOXL2 playing a role in malignant transformation.