gebhart/patrepeval huggingface dataset:
Tissue distribution of an epithelial and tumor-associated antigen recognized by monoclonal antibody F36/22. (1983)

Murine monoclonal antibody F36/22 was derived by immunizing BALB/c mice with human breast cancer cells. This antibody reacts with an antigen located both on differentiated mammary ductal epithelia and on breast carcinomas, as examined by indirect immunoperoxidase techniques. Although the expression of this antigen correlated with estrogen receptor levels of breast tumors, antibody F36/22 did not directly react with estrophilin. In contrast to the expression of classical differentiation antigens, this antigen was found in a high percentage of poorly differentiated carcinomas of the breast. Staining intensities were similar for well- and poorly differentiated tumors; thus, antigen expression was not related to tumor grade. Intratumoral heterogeneity of antigen expression was observed in the majority of tumors. Since a subset (64 of 80) of the breast carcinomas examined have expressed the antigen, McAb 36/22 was of use for the immunological subclassification of tumors which were indistinguishable by conventional histopathological staining techniques. The antigen was also present on other adenocarcinomas (ovary, colon, stomach, pancreas, and prostate); however, these tumors usually exhibited reduced staining intensity compared with that observed in breast cancer. The normal counterpart tissues at these histotypes contained no detectable levels of the antigen, and increased expression of the antigen was associated with tumorigenesis at these sites. Tumors of mesenchymal origin and carcinomas other than adenocarcinomas exhibited undetectable levels of the antigen. Therefore, depending on the organ site, McAb F36/22 recognizes an epithelial and/or tumor-associated antigen.
Cooperative signaling between cytokine receptors and the glucocorticoid receptor in the expansion of erythroid progenitors: molecular analysis by expression profiling (2003)

Erythroid progenitors undergo renewal (proliferation without apparent differentiation) in response to erythropoietin (Epo), stem cell factor (SCF), and glucocorticoids (dexamethasone) (Dex). SCF and Dex cooperate with Epo to promote proliferation and inhibit differentiation of erythroid progenitors, while Epo alone is required to protect erythroid cells from apoptosis during terminal red cell maturation. To examine the mechanism of the synergistic interactions of Epo, SCF, and Dex, we analyzed gene expression patterns using DNA chip-based large-scale comparative gene profiling using microarrays enriched in hematopoietic transcripts or containing randomly selected genes. Differentially regulated genes were validated by real-time reverse transcription-polymerase chain reaction (RT-PCR). The results reveal cooperative regulation of gene expression by glucocorticoids and Epo/SCF on a number of genes, such as CIS, BTG1, VDUP1, CXCR4, GILZ, and RIKEN29300106B05. While Epo and SCF never showed opposite effects on gene expression, Dex either enhanced or attenuated the effect of Epo and/or SCF. Several glucocorticoid receptor (GR)-target genes were regulated by Dex only in the presence of Epo and/or SCF, suggesting that the GR functions in the context of a larger transactivation complex to regulate these genes. The data also suggest that modulation of cytokine-induced signals by the GR is an important mechanism in erythroid progenitor renewal.
Continuous cell-free protein synthesis using glycolytic intermediates as energy sources. (2008)

In this work, we demonstrate that glycolytic intermediates can serve as efficient energy sources to regenerate ATP during continuous-exchange cell-free (CECF) protein synthesis reactions. Through the use of an optimal energy source, approximately 10 mg/ml of protein was generated from CECF protein synthesis reaction at greatly reduced reagent costs. Compared with the conventional reactions utilizing phosphoenol pyruvate as an energy source, the described method yields 10-fold higher productivity per unit reagent cost, making the techniques of CECF protein synthesis more realistic alternative for rapid protein production.
Analysis of MultiplePlasmodium falciparumInfections in Tanzanian Children during the Phase III Trial of the Malaria Vaccine SPf66 (1997)

In the first phase III efficacy trial of the malaria vaccine SPf66 in Africa, MOIs in SPf66- and placebo-vaccinated children were analyzed by polymerase chain reaction-restriction fragment length polymorphism of the Plasmodium falciparum merozoite surface antigen 2 (MSA2). MOIs were significantly reduced in asymptomatic vaccine recipients compared with those in asymptomatic placebo recipients; however, no differences were observed among symptomatic children in the vaccine and control groups. These results show that immunization with SPf66 modulates the course of naturally occurring infections, as reflected by reduced MOIs. In placebo recipients, however, there was a significant negative correlation between numbers of infecting genotypes, as identified by MSA2, and morbidity. Asymptomatic placebo recipients had an average of 5 concurrent infections, whereas children with clinical cases had an average of 3.4 infections. These data provide further evidence that premunition from concurrent infections is important in immunity against clinical malaria. No such effect of multiple infections was found in the vaccinated group.
High contrast organic light-emitting devices with improved electrical characteristics (2006)

High contrast organic light-emitting devices with low-reflection cathodes are fabricated. The cathode consists of a semitransparent metal layer, a phase-changing (PC) layer, and a reflective metal layer. With Al doped tris(8-hydroxyquinoline) aluminum as PC layer, devices exhibit the average reflectivity of the ambient light as low as about 13%. And its electrical characteristics are almost identical to that of a conventional device, although the thickness is increased by 70%. The improvement in conductivity could be attributed to the conductive Al cluster distributed in the organic matrix.
Properties of a New, Long‐Lasting Vaginal Delivery System (LASRS) for Contraceptive and Antimicrobial Agents (2001)

In view of the need for improved vaginal formulations that are contraceptive, that may prevent transmission of sexually transmitted infections, or both, a new delivery system (base formulation; called Long Acting, Sustained Release of Spermicide, or LASRS) was developed that contains bioadhesive and other ingredients with a long history of safety, and was designed to provide long-lasting vaginal retention of the formulation and to minimize possible vaginal irritation caused by incorporated active ingredients. Nonoxynol-9 (N-9) was added as an active ingredient to study the vaginal irritating properties of the formulation and to assess its long-term effectiveness by postcoital spermicidal tests. In the first series of experiments, in vitro studies showed that the formulation spreads rapidly over a cellulose membrane, forming a bioadhesive layer that remained for at least 12 hours. The second series of experiments addressed the safety of the LASRS suppository in rabbits and primates. Even with a very high concentration of N-9 (20.5%), LASRS caused only mild/moderate but acceptable irritation in the rabbit. No vaginal irritation occurred in the primate at an even higher concentration (22.5%). During the third series of experiments, the long-lasting vaginal retention properties were evaluated by postcoital spermicidal tests in the primate. LASRS with N-9 was highly spermicidal even when mating was delayed for 12 hours after placement of the formulation. Spermicidal activity was also observed when 1) mating was delayed for 24 hours after insertion of the formulation, and 2) if the females were mated 2 or even 3 times without reinsertion of the suppository before collection of the vaginal contents. In the final series of tests, the postcoital spermicidal properties of menfegol, another cytotoxic spermicide, were evaluated as were several modifications in the base formulation. Menfegol produced essentially the same results as N-9. Altering the base formulation proved to be nonbeneficial because a decrease in the long-term spermicidal effectiveness was obtained. These results suggest that the LASRS suppository has good vehicle properties for the delivery of active ingredients to the vagina.
Porous Graphene as the Ultimate Membrane for Gas Separation (2009)

We investigate the permeability and selectivity of graphene sheets with designed subnanometer pores using first principles density functional theory calculations. We find high selectivity on the order of 10(8) for H(2)/CH(4) with a high H(2) permeance for a nitrogen-functionalized pore. We find extremely high selectivity on the order of 10(23) for H(2)/CH(4) for an all-hydrogen passivated pore whose small width (at 2.5 A) presents a formidable barrier (1.6 eV) for CH(4) but easily surmountable for H(2) (0.22 eV). These results suggest that these pores are far superior to traditional polymer and silica membranes, where bulk solubility and diffusivity dominate the transport of gas molecules through the material. Recent experimental investigations, using either electron beams or bottom-up synthesis to create pores in graphene, suggest that it may be possible to employ such techniques to engineer variable-sized, graphene nanopores to tune selectivity and molecular diffusivity. Hence, we propose using porous graphene sheets as one-atom-thin, highly efficient, and highly selective membranes for gas separation. Such a pore could have widespread impact on numerous energy and technological applications; including carbon sequestration, fuel cells, and gas sensors.
Novel σ Receptor Ligands. Part 2. SAR of Spiro[[2]benzopyran-1,4‘-piperidines] and Spiro[[2]benzofuran-1,4‘-piperidines] with Carbon Substituents in Position 3 (2002)

Several spiro[[2]benzopyran-1,4'-piperidines] and spiro[[2]benzofuran-1,4'-piperidines] were synthesized and evaluated for their binding properties for sigma(1) and sigma(2) receptors. The key step for the introduction of a one carbon residue is the reaction of the cyclic methyl acetals 2a and 3a with trimethylsilyl cyanide to yield the nitriles 5 and 20. The reaction of the lactols 2b and 3b with stabilized phosphoranes affords spiropiperidines with a two carbon residue in position 3. In agreement with previously reported sigma(1) and sigma(2) receptor binding data, the investigated spiro compounds display higher affinity for sigma(1) vs sigma(2) receptors. Compounds with a cyano group in position 3 of the spirocycle show high sigma(1) receptor affinity and selectivity. The spirobenzopyran nitrile 5 and the homologous spirobenzofuran nitriles 20 and 23 show almost identical sigma(1) affinities, whereas the spirobenzopyran nitrile 13 with a methylene spacer is 10-fold less potent. Among the reported compounds, 1'-benzyl-3,4-dihydrospiro[[2]benzopyran-1,4'-piperidine]-3-carbonitrile 5 represents the most potent sigma(1) receptor ligand with a K(i) value of 1.54 nM and a sigma(1)/sigma(2) selectivity ratio of 1030.
Orally administered, insulin-loaded amidated pectin hydrogel beads sustain plasma concentrations of insulin in streptozotocin-diabetic rats (2000)

We report successful oral administration of insulin entrapped in amidated pectin hydrogel beads in streptozotocin (STZ)-diabetic rats, with a concomitant reduction in plasma glucose concentration. The pectin-insulin (PI) beads were prepared by the gelation of humilin-pectin solutions in the presence of calcium. Separate groups of STZ-diabetic rats were orally administered two PI beads (30 micrograms insulin) once or twice daily or three beads (46 micrograms) once daily for 2 weeks. Control non-diabetic and STZ-diabetic rats were orally administered pectin hydrogel drug-free beads. By comparison with control non-diabetic rats, untreated STZ-diabetic rats exhibited significantly low plasma insulin concentration (0.32+/-0. 03 ng/ml, n=6, compared with 2.60+/-0.44 ng/ml in controls, n=6) and increased plasma glucose concentrations (25.84+/-1.44 mmol/l compared with 10.72+/- 0.52 mmol/l in controls). Administration of two PI beads twice daily (60 micrograms active insulin) or three beads (46 micrograms) once a day to STZ-diabetic rats increased plasma insulin concentrations (0.89+/-0.09 ng/ml and 1.85+/- 0.26 ng/ml, respectively), with a concomitant reduction in plasma glucose concentration (15.45+/-1.63 mmol/l and 10.56+/-0.26 mmol/l, respectively). However, a single dose of PI beads (30 micrograms) did not affect plasma insulin concentrations, although plasma glucose concentrations (17.82+/-2.98 mmol/l) were significantly reduced compared with those in untreated STZ-diabetic rats. Pharmacokinetic parameters in STZ-diabetic rats show that the orally administered PI beads (30 micrograms insulin) were more effective in sustaining plasma insulin concentrations than was s.c. insulin (30 micrograms). The data from this study suggest that this insulin-loaded amidated pectin hydrogel bead formulation not only produces sustained release of insulin, but may also reduce plasma glucose concentration in diabetes mellitus.
Characterisation of 11β-hydroxysteroid dehydrogenase 1 in human orbital adipose tissue: a comparison with subcutaneous and omental fat (2007)

Glucocorticoids (GCs) have a profound effect on adipose biology increasing tissue mass causing central obesity. The pre-receptor regulation of GCs by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) that activates cortisol from cortisone has been postulated as a fundamental mechanism underlying the metabolic syndrome mediating adipocyte hyperplasia and hypertrophy in the omental (OM) depot. Orbital adipose tissue (OF) is the site of intense inflammation and tissue remodelling in several orbital inflammatory disease states. In this study, we describe features of the GC metabolic pathways in normal human OF depot and compare it with subcutaneous (SC) and OM depots. Using an automated histological characterisation technique, OF adipocytes were found to be significantly smaller (parameters: area, maximum diameter and perimeter) than OM and SC adipocytes (P<0 x 001). Although immunohistochemical analyses demonstrated resident CD68+ cells in all three whole tissue adipose depots, OF CD68 mRNA and protein expression exceeded that of OM and SC (mRNA, P<0 x 05; protein, P<0 x 001). In addition, there was higher expression of glucocorticoid receptor (GR)alpha mRNA in the OF whole tissue depot (P<0 x 05). Conversely, 11beta-HSD1 mRNA together with the markers of late adipocyte differentiation (FABP4 and G3PDH) were significantly lower in OF. Primary cultures of OF preadipocytes demonstrated predominant 11beta-HSD1 oxo-reductase activity with minimal dehydrogenase activity. Orbital adipocytes are smaller, less differentiated, and express low levels of 11beta-HSD1 but abundant GRalpha compared with SC and OM. OF harbours a large CD68+ population. These characteristics define an orbital microenvironment that has the potential to respond to sight-threatening orbital inflammatory disease.
Loss of function of def selectively up-regulates Δ113p53 expression to arrest expansion growth of digestive organs in zebrafish (2005)

Transcription factor p53 forms a network with associated factors to regulate the cell cycle and apoptosis in response to environmental stresses. However, there is currently no direct genetic evidence to show if or how the p53 pathway functions during organogenesis. Here we present evidence to show that the zebrafish def (digestive-organ expansion factor) gene encodes a novel pan-endoderm-specific factor. A loss-of-function mutation in def confers hypoplastic digestive organs and selectively up-regulates the expression of Delta113p53, counterpart to a newly identified isoform of p53 produced by an alternative internal promoter in intron 4 of the p53 gene in human. The increased Delta113p53 expression is limited to within the mutant digestive organs, and this increase selectively induces the expression of p53-responsive genes to trigger the arrest of the cell cycle but not apoptosis, resulting in compromised organ growth in the mutant. Our data demonstrate that, while induction of expression of p53 and/or its isoforms is crucial to suppress abnormal cell growth, Delta113p53 is tightly regulated by an organ/tissue-specific factor Def, especially during organogenesis, to prevent adverse inhibition of organ/tissue growth.
Imatinib mesylate inhibits the profibrogenic activity of TGF-β and prevents bleomycin-mediated lung fibrosis (2004)

Idiopathic pulmonary fibrosis is a progressive and fatal fibrotic disease of the lungs with unclear etiology. Prior efforts to treat idiopathic pulmonary fibrosis that focused on anti-inflammatory therapy have not proven to be effective. Recent insight suggests that the pathogenesis is mediated through foci of dysregulated fibroblasts driven by profibrotic cytokine signaling. TGF-β and PDGF are 2 of the most potent of these cytokines. In the current study, we investigated the role of TGF-β–induced fibrosis mediated by activation of the Abelson (Abl) tyrosine kinase. Our data indicate that fibroblasts respond to TGF-β by stimulating c-Abl kinase activity independently of Smad2/3 phosphorylation or PDGFR activation. Moreover, inhibition of c-Abl by imatinib prevented TGF-β–induced ECM gene expression, morphologic transformation, and cell proliferation independently of any effect on Smad signaling. Further, using a mouse model of bleomycin-induced pulmonary fibrosis, we found a significant inhibition of lung fibrosis by imatinib. Thus, Abl family members represent common targets for the modulation of profibrotic cytokine signaling.
A scheme for data compression in supercomputers (1988)

There is a growing recognition of the importance of efficient coding and data compression schemes in supercomputing centers and in networks of high-speed computing machines. Recently, there has been a considerable interest in arithmetic coding as a promising technique for reducing the cost of data storage and transmission. In this paper, we present a compression algorithm that is tailored to utilize the enormous speed and memory size of supercomputers and which utilizes an enhanced arithmetic coding scheme. The paper also presents efficient VLSI designs for the enhanced scheme. These hardware designs are suitable for inclusion in disk and communication controllers of supercomputers and would provide a practical way to effectively increase thresholds of data transfer rates and communication bandwidth.
A Fault Tolerant NoC Architecture for Reliability Improvement and Latency Reduction (2009)

With reducing feature size of transistors and increasing number of cores on a single chip, fault tolerance and reliability have become two significant challenges for IC designers. Since chip design is extremely cost-sensitive, the fault tolerance redundancy must be provided at a reasonable cost. In this paper, a fault tolerant NoC architecture with cores linked to two switches instead of one, is proposed. This architecture is able to save cores with a faulty switch. Also, to be more efficient and to compensate this redundancy, a new routing algorithm is suggested that can be dynamically reconfigured to escape faulty switches. According to evaluation of the proposed architecture, latency and reliability are improved.
Evaluating Web-based Question Answering Systems (2002)

The official evaluation of TREC-style Q&amp;amp;A systems is done manually, which is quite expensive and not scalable to web-based Q&amp;amp;A systems. An automatic evaluation technique is needed for dynamic Q&amp;amp;A systems. This paper presents a set of metrics that have been implemented in our web-based Q&amp;amp;A system, namely NSIR. It also shows the correlations between the different metrics. 1.
Pulsed and Continous Radiofrequency Current Adjacent to the Cervical Dorsal Root Ganglion of the Rat Induces Late Cellular Activity in the Dorsal Horn (2004)

The authors demonstrated a late neuronal activity in the dorsal horn after exposure of the cervical dorsal root ganglion to different radiofrequency modalities, which was not temperature dependent.
Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma (2016)

Immunomodulatory effects of PD-1 inhibition were demonstrated through multiple lines of evidence across nivolumab doses. Biomarker changes from baseline reflect nivolumab pharmacodynamics in the tumor microenvironment. These data may inform potential combinations. Clin Cancer Res; 22(22); 5461-71. ©2016 AACR.
Blocking Spinal CCR2 with AZ889 Reversed Hyperalgesia in a Model of Neuropathic Pain (2010)

Overall, this study strengthens the important role of CCR2 in neuropathic pain and highlights feasibility that interfering on this mechanism at the spinal level with a selective antagonist can provide new analgesia opportunities.
Molecular Cloning and Structure of the Human Transforming Growth Factor-β2 Gene Promoter (1991)

Genomic DNA extending over 10 kb 5' of the transforming growth factor-beta 2 (TGF-beta 2) coding region was isolated from a human lung fibroblast lambda phage library. A 5.6 kb Hind III fragment containing the 5'-untranslated region and flanking sequences was subcloned and sequenced. S1 nuclease protection analysis identified a transcriptional initiation site 1357 nucleotides 5' of the methionine initiation codon (ATG). A "TATA box" consensus sequence was identified 30 bp from this transcriptional start site; however, consensus "CAT box" sequences were not observed. Approximately 50 nucleotides of homopurine-pyrimidine [d(GA.CT)50] sequence were identified in the 5'-untranslated region, as well as two short open reading frames of 5 and 45 amino acids. Several AP-1, AP-2, CRE and SP1-like DNA consensus sequence elements were also identified surrounding the transcription initiation site. 5'-deletion mutants of the promoter region were fused to the chloramphenicol acetyl transferase (CAT) gene and promoter activity of the isolated genomic DNA was demonstrated in several cell lines. DNA constructs containing nucleotides between -508 to +63 demonstrated high levels of promoter activity. However, sequences between -778 and -508 nucleotides modulated this promoter activity in a manner which was dependent upon the cell line utilized, suggesting that regulation of TGF-beta 2 gene transcription may be dependent upon the cellular background. The TGF-beta 2 promoter is markedly different from the promoters that have been recently characterized for TGF-beta 1 and TGF-beta 3.