gebhart/patrepeval huggingface dataset:
Chronic Inhibition of Dipeptidyl Peptidase-4 With a Sitagliptin Analog Preserves Pancreatic β-Cell Mass and Function in a Rodent Model of Type 2 Diabetes (2006)

Inhibitors of dipeptidyl peptidase-4 (DPP-4), a key regulator of the actions of incretin hormones, exert antihyperglycemic effects in type 2 diabetic patients. A major unanswered question concerns the potential ability of DPP-4 inhibition to have beneficial disease-modifying effects, specifically to attenuate loss of pancreatic beta-cell mass and function. Here, we investigated the effects of a potent and selective DPP-4 inhibitor, an analog of sitagliptin (des-fluoro-sitagliptin), on glycemic control and pancreatic beta-cell mass and function in a mouse model with defects in insulin sensitivity and secretion, namely high-fat diet (HFD) streptozotocin (STZ)-induced diabetic mice. Significant and dose-dependent correction of postprandial and fasting hyperglycemia, HbA(1c), and plasma triglyceride and free fatty acid levels were observed in HFD/STZ mice following 2-3 months of chronic therapy. Treatment with des-fluoro-sitagliptin dose dependently increased the number of insulin-positive beta-cells in islets, leading to the normalization of beta-cell mass and beta-cell-to-alpha-cell ratio. In addition, treatment of mice with des-fluoro-sitagliptin, but not glipizide, significantly increased islet insulin content and improved glucose-stimulated insulin secretion in isolated islets. These findings suggest that DPP-4 inhibitors may offer long-lasting efficacy in the treatment of type 2 diabetes by modifying the courses of the disease.
Abcc10 status affects mammary tumour growth, metastasis, and docetaxel treatment response (2014)

These data identify roles for Abcc10 in breast cancer pathogenesis and in vivo docetaxel resistance.
JNK and c‐Jun but not ERK and c‐Fos are associated with sustained neointima‐formation after balloon injury (2000)

These findings demonstrate a clear association between MAP-kinases and their transcription factor substrates in vivo with a predominant association of JNK and c-Jun with sustained SMC proliferation.
Endocarditis risk of the USCI PDA umbrella for transcatheter closure of patent ductus arteriosus. (1994)

In this animal model, presence of a significant PDA shunt (with or without a PDA Umbrella present) results in significantly increased susceptibility to endarteritis and endocarditis. The PDA Umbrella device does not appear to be susceptible to direct infection as early as 2 weeks after implantation if it is properly located in the ductus arteriosus. Animals with no shunt or a trivial shunt are no more susceptible to developing endocarditis 2 weeks after PDA Umbrella implantation than are controls.
Synthesis of Bispecific Antibodies using Genetically Encoded Unnatural Amino Acids (2012)

Bispecific antibodies were constructed using genetically encoded unnatural amino acids with orthogonal chemical reactivity. A two-step process afforded homogeneous products in excellent yield. Using this approach, we synthesized an anti-HER2/anti-CD3 bispecific antibody, which efficiently cross-linked HER2+ cells and CD3+ cells. In vitro effector-cell mediated cytotoxicity was observed at picomolar concentrations.
A Prospective Comparative Clinical Analysis of the First-Generation Knee Replacements (1979)

A prospective study of 119 polycentric and 92 geometric knee replacements was performed to determine and compare the clinical effectiveness of these two prostheses. All kneex were followed for a minimum of 2 years and a mean time of 3 1/2 years (2--6 years). Data were collected using a specially designed proforma for subsequent computer analysis. Failure occurred in 11% of the polycentric and in 16% of the geometric knees. Males (8 of 47) and patients with osteoarthritic knees (22 of 68) failed most frequently. Both prostheses provided excellent relief of pain, the same degree of flexion and improvement in flexion contracture. However, walking, function, alignment, stability, muscle strength and patellar mobility varied as to the degree of improvement and the type of prosthesis. Present results with prosthetic knee replacement using a completely new operative technique can be used as a basis for comparison with other contemporary and future arthroplasty designs.
Rapid and Efficient Vascular Transport of Arginine Polymers Inhibits Myointimal Hyperplasia (2000)

Short polymers of arginine have the unique ability of vascular cell translocation, and they also have direct biological effects. These attributes are potentially useful in treating myointimal hyperplasia.
In vivo interferon regulatory factor 3 tumor suppressor activity in B16 melanoma tumors. (2002)

Delivery of transcription factors to cancer cells to reprogram gene expression may represent a novel strategy to augment the production of immune stimulatory cytokines and trigger a more potent antitumor response. In the present study, a bicistronic retroviral vector (AP2) was used to transduce B16-F0 melanoma cells with IFN regulatory factor (IRF)-3, which has been shown to activate type I IFN genes (IFN-beta and IFN-alpha) as well as other cytokines. Gene-modified B16 melanoma cells were inoculated s.c. into C57BL/6 syngeneic mice. In animals receiving IRF-3 B16 melanoma cells, tumors grew at a 4- to 5-fold reduced rate, and tumors that developed from these mice had a moderate-to-dense infiltration of inflammatory cells, whereas only low levels of lymphocyte infiltration were observed in mock-transduced B16 tumors. Furthermore, tumor growth was not inhibited in severe-combined immunodeficient mice after inoculation of IRF-3-expressing B16 cells, which suggested that IRF-3-mediated antitumor responses were dependent on a functional adaptive lymphocyte response. Interestingly, these in vivo effects on tumor growth correlated with higher mRNA expression of chemokines such as MIP-1beta, RANTES, and IP-10, as well as dramatic increases in vitro in the inducibility of cytokine mRNA such as IFN-beta, TNF-alpha and interleukin 6. Our results demonstrate that with weakly antigenic tumors such as B16 melanoma, IRF-3 gene transfer can mediate important antitumor responses. These findings suggest a novel role for IRF-3 as a potential molecular target for gene therapy of cancer.
Sustained Small Interfering RNA Delivery by Mesoporous Silicon Particles (2010)

RNA interference (RNAi) is a powerful approach for silencing genes associated with a variety of pathologic conditions; however, in vivo RNAi delivery has remained a major challenge due to lack of safe, efficient, and sustained systemic delivery. Here, we report on a novel approach to overcome these limitations using a multistage vector composed of mesoporous silicon particles (stage 1 microparticles, S1MP) loaded with neutral nanoliposomes (dioleoyl phosphatidylcholine, DOPC) containing small interfering RNA (siRNA) targeted against the EphA2 oncoprotein, which is overexpressed in most cancers, including ovarian. Our delivery methods resulted in sustained EphA2 gene silencing for at least 3 weeks in two independent orthotopic mouse models of ovarian cancer following a single i.v. administration of S1MP loaded with EphA2-siRNA-DOPC. Furthermore, a single administration of S1MP loaded with-EphA2-siRNA-DOPC substantially reduced tumor burden, angiogenesis, and cell proliferation compared with a noncoding control siRNA alone (SKOV3ip1, 54%; HeyA8, 57%), with no significant changes in serum chemistries or in proinflammatory cytokines. In summary, we have provided the first in vivo therapeutic validation of a novel, multistage siRNA delivery system for sustained gene silencing with broad applicability to pathologies beyond ovarian neoplasms.
Facile and Scalable Synthesis of Monodispersed Spherical Capsules with a Mesoporous Shell (2010)

Monodispersed hollow spherical mesoporous particles with tunable particle size and shell thickness were readily synthesized using latex templates and a silica precursor in a weakly basic ethanol−water mixture.
On Sequential Sampling for Global Metamodeling in Engineering Design (2002)

Approximation models (also known as metamodels) have been widely used in engineering design to facilitate analysis and optimization of complex systems that involve computationally expensive simulation programs. The accuracy of metamodels is directly related to the sampling strategies used. Our goal in this paper is to investigate the general applicability of sequential sampling for creating global metamodels. Various sequential sampling approaches are reviewed and new approaches are proposed. The performances of these approaches are investigated against that of the one-stage approach using a set of test problems with a variety of features. The potential usages of sequential sampling strategies are also discussed.
A segmentation method of textured image by using neural network (2005)

This paper deals with a segmentation method of an image composed of some kinds of textures with randomness using a neural network. After a texture image is divided into a number of small windows with the same size, the feature vector in those windows is extracted by using a two-dimensional autoregressive model and fractal dimension. The clustering of feature vectors is performed by applying the self-organization algorithm developed by Kohonen, and the result of clustering is mapped onto the original image. Furthermore, a method which applies the backpropagation algorithm to the result of clustering is proposed to improve the accuracy of segmentation.
BCL9 provides multi-cellular communication properties in colorectal cancer by interacting with paraspeckle proteins (2020)

Colorectal cancer (CRC) is the third most commonly diagnosed cancer, which despite recent advances in treatment, remains incurable due to molecular heterogeneity of tumor cells. The B-cell lymphoma 9 (BCL9) oncogene functions as a transcriptional co-activator of the Wnt/β-catenin pathway, which plays critical roles in CRC pathogenesis. Here we have identified a β-catenin-independent function of BCL9 in a poor-prognosis subtype of CRC tumors characterized by expression of stromal and neural associated genes. In response to spontaneous calcium transients or cellular stress, BCL9 is recruited adjacent to the interchromosomal regions, where it stabilizes the mRNA of calcium signaling and neural associated genes by interacting with paraspeckle proteins. BCL9 subsequently promotes tumor progression and remodeling of the tumor microenvironment (TME) by sustaining the calcium transients and neurotransmitter-dependent communication among CRC cells. These data provide additional insights into the role of BCL9 in tumor pathogenesis and point towards additional avenues for therapeutic intervention.
An Intramolecular Cyclization of Phenol Derivatives Bearing Aminoquinones Using a Hypervalent Iodine Reagent (1996)

The hypervalent iodine oxidation of phenol derivatives bearing aminoquinones at the ortho (9) or meta positions (19) in 2,2,2-trifluoroethanol was investigated with the aim of preparing novel antitumor compounds. Azacarbocyclic spirodienone derivatives (13) or phenol derivatives containing the 2,3-dihydro-1H-azepine systems (17, 20) were selectively obtained by the reaction of these phenol derivatives and the hypervalent iodine reagent, phenyliodine(III) bis(trifluoroacetate). The application of this reaction to phenol derivatives bearing aminoquinones (10−12) is also described.
A RecA Homologue in Ustilago maydis That Is Distinct and Evolutionarily Distant from Rad51 Actively Promotes DNA Pairing Reactions in the Absence of Auxiliary Factors (2001)

Two RecA homologues have been identified to date in Ustilago maydis. One is orthologous to Rad51 while the other, Rec2, is structurally quite divergent and evolutionarily distant. DNA repair and recombination proficiency in U. maydis requires both Rec2 and Rad51. Here we have examined biochemical activities of Rec2 protein purified after overexpression of the cloned gene. Rec2 requires DNA as a cofactor to hydrolyze ATP and depends on ATP to promote homologous pairing and DNA strand exchange. ATPgammaS was found to substitute for ATP in all pairing reactions examined. With superhelical DNA and a homologous single-stranded oligonucleotide as substrates, Rec2 actively promoted formation and dissociation of D-loops. When an RNA oligonucleotide was substituted it was found that R-loops could also be formed and utilized as primer/template for limited DNA synthesis. In DNA strand exchange reactions using oligonucleotides, we found that Rec2 exhibited a pairing bias that is opposite that of RecA. Single-stranded oligonucleotides were activated for DNA strand exchange when attached as tails protruding from a duplex sequence due to enhanced binding of Rec2. The results indicate that Rec2 is competent, and in certain ways even better than Rad51, in the ability to provide the fundamental DNA pairing activity necessary for recombinational repair. We propose that the emerging paradigm for homologous recombination featuring Rad51 as the essential catalytic component for strand exchange may not be universal in eukaryotes.
Exploring the Molecular Mechanisms Underlying the Protective Effects of Microbial SCFAs on Intestinal Tolerance and Food Allergy (2020)

A body of evidence suggests that food allergy (FA) has increased in prevalence over the past few decades. Novel findings support the hypothesis that some commensal bacteria and particularly microbial metabolites might contribute to development of oral tolerance and prevention from FA. Recently, beneficial effects of short-chain fatty acids (SCFAs), the main class of gut microbiota-derived metabolites, on FA have been proposed. The intestinal SCFAs are major end products during bacterial fermentation of complex and non-digestible carbohydrates such as dietary fiber. The multifaceted mechanisms underlying beneficial effects of SCFAs on the mucosal immune system comprise the regulation of diverse cellular pathways in epithelial, dendritic, and T cells, as well as the impact on the immunometabolism and epigenetic status of regulatory lymphocytes. Of note, SCFAs are effective inhibitors of histone deacetylases (HDACs). As a consequence, SCFAs appear to be implicated in attenuation of intestinal inflammation and autoimmune diseases. In this review, we will discuss the recent development in this research area by highlighting the role of the individual SCFAs acetate, propionate, butyrate, and pentanoate in promoting the differentiation of regulatory T and B cells and their potential beneficial effects on the prevention of FA. In this context, targeted alterations in the gut microbiota in favor of SCFA producers or supplementation of medicinal food enriched in SCFAs could be a novel therapeutic concept for FA.
Total serum sialic acid concentration as a supporting marker of malignancy in ovarian neoplasia. (1999)

The present study was undertaken to establish the diagnostic utility of total sialic acid (SA) determination in the serum of patient with ovarian neoplasia. In a group of 29 patients with histopathologically confirmed ovarian neoplasia, concentrations of total SA was determined. In addition, the two tumor markers: CA125 antigen level and lactic dehydrogenase (LDH) activity were determined. The mean value of serum total SA in patients (1.76 mmol/L) was significantly higher than in the control group of healthy women (1.52 mmol/L). The elevation of serum total SA was associated with the burden of the tumor: higher total SA levels were observed in the cases of more developed malignancies. A significant correlation has been found between serum total SA content and CA125 level in patients with undifferentiated ovarian cancers. It has been concluded that total serum sialic acid level reflects the development of malignancy and should be considered as a supporting tumor marker in ovarian cancer diagnosis.
Syntheses and Reactions of Polycationically Substituted Azido‐ and Diazidobenzenes (2007)

Abstract The increased reactivity of hexakis[4‐(dimethylamino)‐1‐pyridinio]benzene hexakis(trifluoromethanesulfonate) ( 1 ) towards nucleophilic substitution of DMAP + ligands was used for the syntheses of the corresponding pentacationically substituted azidobenzene and the tetracationically substituted o ‐diazidobenzene. In contrast to unsubstituted azido‐ and diazidobenzene, the latter compounds are stable towards heat or shock. Predominantly due to the strong electrostatic effects provided by the polycationically substituted phenyl(ene) moieties, the corresponding triphenylphosphazides are stable at room temperature. Application of the Staudinger reaction yielded the corresponding polyonio‐substituted aniline and o ‐phenylenediamine, respectively.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)
Molecular analysis of the Alcaligenes eutrophus poly(3-hydroxybutyrate) biosynthetic operon: identification of the N terminus of poly(3-hydroxybutyrate) synthase and identification of the promoter (1991)

Molecular methods have been applied to analyze the expression of the Alcaligenes eutrophus poly(3-hydroxybutyrate) (PHB) synthase gene (phbC). The translational initiation codon was identified by analysis of the amino acid sequence of a PHB synthase-beta-galactosidase fusion protein. This protein was purified to almost gel electrophoretic homogeneity by chromatography on DEAE-Sephacel and on aminophenyl-beta-D-thiogalactopyranoside-Sepharose from cells of A. eutrophus which harbored a phbC'-'lacZ fusion gene. A sequence (TTGACA-18N-AACAAT), exhibiting striking homology to the Escherichia coli sigma 70 promoter consensus sequence, was identified approximately 310 bp 5' upstream from the translation initiation codon. An S1 nuclease protection assay mapped the transcription start point of phbC 6 bp downstream from this promoter. The location of the promoter was confirmed by analyzing the expression of active PHB synthase in clones of E. coli harboring 5' upstream deletions of phbC ligated to the promoter of the lacZ gene (lacZp) in a Bluescript vector. Plasmids do181 and do218, which were deleted for the first 108 or 300 bp of the phbC structural gene, respectively, conferred the ability to synthesize large amounts of different truncated PHB synthase proteins to the cells. These proteins contributed to approximately 10% of the total cellular protein as estimated from sodium dodecyl sulfate-polyacrylamide gels. The modified PHB synthase encoded by plasmid do181 was still active. Clones in which the lacZp-'phbC fusion harbored the complete phbC structural gene plus the phbC ribosome binding site did not overexpress PHB synthase.
Substratum Stiffness and Latrunculin B Regulate Matrix Gene and Protein Expression in Human Trabecular Meshwork Cells (2012)

Substratum stiffness impacts HTM matrix gene and protein expression and modulates the impact of Lat-B treatment on the expression of these matrix proteins. Integrating the use of biologically relevant substratum stiffness in the conduction of in vitro experiments gives important insights into HTM cell response to drugs that may more accurately predict responses observed in vivo.
Utilization of Unlabeled Probes for the Detection of Fibroblast Growth Factor Receptor 2 Exons 7 and 12 Mutations in Endometrial Carcinoma (2011)

Background Endometrial adenocarcinomas are associated with a variety of molecular abnormalities including microsatellite instability, Kirsten rat sarcoma viral oncogene homolog mutations, and phosphatase and tensin homolog inactivation. Recently, mutations in fibroblast growth factor receptor 2 (FGFR2) have been described but their frequency and clinicopathologic characteristics are incompletely known. Methods To determine the frequency of mutations in FGFR2 exons 7 and 12, 43 adenocarcinomas of the endometrium were studied by high-resolution melting analysis utilizing unlabeled probes and sequencing. Results Three of 43 (7%) endometrial carcinomas harbored FGFR2 exon 7 mutations. All 3 mutations were S252W and occurred in endometrioid (type I) adenocarcinomas. Direct sequencing indicated that 2 of the S252W mutations were heterozygous, whereas 1 was presumably homozygous. No FGFR2 mutations were detected in exon 12. Conclusions FGFR2 mutations occur in approximately 7% of adenocarcinomas of the endometrium. Only carcinomas of an endometrioid morphology contain FGFR2 mutations, and in our series all were S252W. FGFR2 exons 7 and 12 unlabeled DNA probes allow for easy screening of endometrial carcinoma for the 2 most common FGFR2 mutations (S252W and N550K). Identification of these mutations may have important implications in directed molecular therapy.
Association of tyrosine protein kinase Zap-70 with the protooncogene product p120c-cbl in T lymphocytes. (1996)

Accumulating data show that the tyrosine protein kinase Zap-70 plays an essential role in T cell receptor-mediated signal transduction. However, the model of action, as well as the physiologically relevant substrates of Zap-70, have not been determined. We have attempted to identify a 120-kD tyrosine-phosphorylated protein (p120) that associates with Zap-70 in activated T lymphocytes. The results of our analyses showed that p120 is largely encoded by the c-cbl protooncogene. Furthermore, the association of Zap-70 with c-Cbl was shown to be induced by T cell receptor stimulation, implying that it required posttranslational modification of one or both of these products. FynT, but not Lck, also associated with c-Cbl in activated T cells. Finally, using a heterologous system, it was demonstrated that the ability of Zap-70 to cause tyrosine phosphorylation of p120c-cbl was dependent on Lck- or FynT-mediated signals. As c-Cbl can associate with several other signaling molecules, it may couple Zap-70 to downstream effectors during T cell activation.
Verification of Caregraph (trademark) Peak Skin Dose Data Using Radiochromic Film (2005)

Abstract : Radiation-induced skin injury during fluoroscopically guided interventional procedures has become an important concern and has been documented for interventional neuroradiology and cardiology procedures.1-4 The risk to any location on the skin increases with the radiation dose to that portion of the skin,3,5,6 and the maximum dose delivered to any portion of the skin during a procedure (the peak skin dose) determines the risk of injury at that point.7,8 Peak skin dose (PSD) may be determined using x-ray film or thermoluminescent dosimeters , but neither provides real-time data. A software program called Caregraph estimates PSD in real-time based on information from the fluoroscopic unit to which it is linked. The purpose of this study was to compare the skin dose estimates produced by Caregraph with the PSD data determined with radiochromic dosimetry film placed against the surface of a tissue-simulating phantom inconfigurations simulating actual clinical situations. The radiochromic film was calibrated to include backscatter values at the National Institute of Standards and Technology.