gebhart/patrepeval huggingface dataset:
CsI:Tl+,Yb2+: ultra-high light yield scintillator with reduced afterglow (2014)

Simultaneous improvement in afterglow, light yield and energy resolution in CsI:Tl-based scintillators paves the way to its application in computer tomography and high-speed imaging.
Nature of Pharmacophore Influences Active Site Specificity of Proteasome Inhibitors (2010)

Proteasomes degrade most proteins in mammalian cells and are established targets of anti-cancer drugs. The majority of proteasome inhibitors are composed of short peptides with an electrophilic functionality (pharmacophore) at the C terminus. All eukaryotic proteasomes have three types of active sites as follows: chymotrypsin-like, trypsin-like, and caspase-like. It is widely believed that active site specificity of inhibitors is determined primarily by the peptide sequence and not the pharmacophore. Here, we report that active site specificity of inhibitors can also be tuned by the chemical nature of the pharmacophore. Specifically, replacement of the epoxyketone by vinyl sulfone moieties further improves the selectivity of β5-specific inhibitors NC-005, YU-101, and PR-171 (carfilzomib). This increase in specificity is likely the basis of the decreased cytotoxicity of vinyl sulfone-based inhibitors to HeLa cells as compared with that of epoxyketone-based inhibitors.
The dose‐duration effect of sodium cromoglycate in exercise‐induced asthma (1984)

Eight patients with exercise-induced asthma participated in a single blind dose-duration study comparing the protective effect of inhaled sodium cromoglycate (SCG) in increasing concentrations from 2 to 40 g/l. Saline was used as a control. Effects were assessed from the mean maximal fall in forced expiratory volume in 1 sec (FEV1) after running on a treadmill for 8 min at 20, 150 and 270 min after drug administration. There was no significant difference between the mean baseline values of FEV1, before and after inhalation of saline and SCG on 4 days of exercise testing. In addition, the maximal percentage falls in FEV1 in the three control exercise tests carried out at 20, 150 and 270 min after inhalation of saline were also comparable. The mean percentage fall in FEV1 (s.e.m.) after saline, SCG 2 g/l, SCG 20 g/l and SCG 40 g/l were 29.3 (4.4), 11.7 (4.5), 8.3 (3.1) and 9.4 (2.3) respectively in the first test at 20 min and 24.5 (5.1), 14.9 (4.2), 13.1 (2.5) and 13.7 (2.8) respectively in the second test at 150 after treatment. The inhibitory effect of SCG was statistically significant at all the concentrations used and the protection offered by the three concentrations of SCG was comparable. In the third exercise test at 270 min after treatment, the mean maximum percentage change after saline, SCG 2 g/l, SCG 20 g/l and SCG 40 g/l were 26.1 (4.8), 23.0 (6.1), 16.6 (5.0) and 15.8 (4.7) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
A Comparison of Intravenous Versus Intraperitoneal Chemotherapy for the Initial Treatment of Ovarian Cancer (1995)

Kirmani, Saeeda; Braly, Patricia S.; McClay, Edward F.; Saltzstein, Sidney L.; Plaxe, Steven C.; Kim, Sinil; Cates, Charles; Howell, Stephen B.Author Information
Oligonucleotide properties determination and primer designing: a critical examination of predictions (2005)

The details of the oligonucleotides and of the different modules of T(m) prediction considered for the study are provided as Supplementary Information, available at Bioinformatics online.
Cellular localization domains of a rabbit and a human carboxylesterase: influence on irinotecan (CPT-11) metabolism by the rabbit enzyme. (1998)

Enzyme activation of prodrugs to improve the therapeutic index of specific anticancer agents is an attractive alternative to current chemotherapy regimens. This study addresses the potential for activating irinotecan (CPT-11) with recombinant carboxylesterases (CEs). CEs are a ubiquitous class of enzymes thought to be involved in the detoxification of xenobiotics. Their primary amino acid sequence indicates that these proteins should be localized to the endoplasmic reticulum. By PCR-mediated mutagenesis of a rabbit liver and a human alveolar macrophage CE cDNA, expression in Cos7 cells, and subsequent immunohistochemical localization, we have determined that an 18-amino acid NH2-terminal hydrophobic signal peptide is responsible for the localization of these proteins to the endoplasmic reticulum. By similar approaches, we have demonstrated that the COOH-terminal amino acids HIEL prevent secretion of the proteins from the cell. Enzymatic activity was lost by removing the NH2-terminal domain; however, active enzyme could be detected in the culture media of cells expressing the COOH-terminally truncated proteins. Secretion of CEs lacking the six COOH-terminal amino acids could be prevented with brefeldin A, confirming that these truncated enzymes were processed and released from cells by endoplasmic reticulum-mediated exocytosis. Double-truncation mutant enzymes lacking both NH2- and COOH-terminal sequences demonstrated immunostaining patterns similar to those of the NH2-terminally truncated proteins and also lacked CE activity. In all cases, metabolism of the classic esterase substrate o-nitrophenyl acetate predicted the sensitivity of cells expressing the rabbit CE to the anticancer agent CPT-11. In addition, the secreted enzyme sensitized Cos7 cells to this drug, indicating that protein association with a lipid bilayer is not required for substrate metabolism.
Polarization fields (2011)

We introduce polarization field displays as an optically-efficient design for dynamic light field display using multi-layered LCDs. Such displays consist of a stacked set of liquid crystal panels with a single pair of crossed linear polarizers. Each layer is modeled as a spatially-controllable polarization rotator, as opposed to a conventional spatial light modulator that directly attenuates light. Color display is achieved using field sequential color illumination with monochromatic LCDs, mitigating severe attenuation and moiré occurring with layered color filter arrays. We demonstrate such displays can be controlled, at interactive refresh rates, by adopting the SART algorithm to tomographically solve for the optimal spatially-varying polarization state rotations applied by each layer. We validate our design by constructing a prototype using modified off-the-shelf panels. We demonstrate interactive display using a GPU-based SART implementation supporting both polarization-based and attenuation-based architectures. Experiments characterize the accuracy of our image formation model, verifying polarization field displays achieve increased brightness, higher resolution, and extended depth of field, as compared to existing automultiscopic display methods for dual-layer and multi-layer LCDs.
Increased tight junctional permeability is associated with the development of colon cancer (1999)

Epithelial tissues act as barriers between two fluid compartments, and the epithelial barrier function is provided by the epithelial cells and the tight junctions (TJs) that connect them. We have shown previously that chronic treatment of a cultured epithelial monolayer with phorbol ester tumor promoters induces an increase in transepithelial paracellular permeability and produces tumor-like polyps, suggesting an association between TJ permeability and tumor formation. In this study, we analyzed the association between TJ permeability and formation of tumors in vivo. The permeability of the TJs was assessed in normal human and rat colon epithelia and in colon tumors by measuring the transepithelial electrical resistance, the paracellular flux rate of D-[(14)C]mannitol and the electron microscopic evaluation of the penetration of the electron dense dye ruthenium red across the TJs. By these criteria, the TJs of human colon tumors, including carcinomas and adenomatous polyps, and the TJs of 1,2-dimethylhydrazine (DMH)-induced rat colon tumors were leakier than the TJs of normal colon. Treatment of rats with the carcinogen DMH induced a progressive increase in the number of aberrant colonic crypts, considered the putative pre-neoplastic colonic phenotype while increasing TJ permeability of the colon epithelium prior to the development of tumors. These results showed that increased TJ permeability of the colon epithelium and consequently a decrease in epithelial barrier function precede the development of colon tumors.
Molecular characterization of the pH‐inducible and growth phase‐dependent promoter P170 of Lactococcus lactis (1999)

In a previous study, we described the use of transposon Tn917-LTV1 for identification of environmentally regulated promoters in Lactococcus lactis. Here, we report the molecular analysis of one of these promoters, P170, that is upregulated at low pH during the transition to stationary phase. The minimal DNA region required for both promoter activity and pH regulation was mapped to a 51 bp fragment located 7 bp upstream of the transcriptional start site. This fragment lacked the consensus -35 promoter region, but it contained an 'extended' -10 promoter region. When a 28 bp segment, containing the consensus -35 region and 22 bp upstream of this in a constitutive promoter, was replaced with the corresponding sequence of P170, the hybrid promoter became regulated by pH and growth phase. This demonstrates that the P170 segment contains a cis-acting sequence involved in the control of promoter regulation. Transcriptional analysis showed that P170 is responsible for the transcription of a monocistronic gene orfX encoding a polypeptide homologous to a hypothetical protein from Bacillus subtilis. Analysis of total RNA from L. lactis grown at constant pH confirmed that transcription from P170 was induced between pH 6.5 and pH 6.0, but only when the culture entered stationary phase. Deletion analysis and chemical mutagenesis of P170 defined a specific region within the untranslated mRNA leader that is able to modulate the expression level directed by the P170 promoter. Deletion of a 72 bp HaeIII fragment from this leader region resulted in a 150- to 200-fold increase in the level of gene expression, without affecting the regulation. The functionality was confirmed by introducing this modulating element downstream of other lactococcal promoters.
On the feasibility of online malware detection with performance counters (2013)

The proliferation of computers in any domain is followed by the proliferation of malware in that domain. Systems, including the latest mobile platforms, are laden with viruses, rootkits, spyware, adware and other classes of malware. Despite the existence of anti-virus software, malware threats persist and are growing as there exist a myriad of ways to subvert anti-virus (AV) software. In fact, attackers today exploit bugs in the AV software to break into systems.
Microfluidic Synthesis of Reversibly Swelling Porous Polymeric Microcapsules with Controlled Morphology (2008)

Porous microcapsules formed from polymer-peptide conjugated macromolecules (see figure) are synthesized by the innovative conjunction of microfluidics with block copolymer self-assembly in flow- focusing microchannel. Reversibility of surface nanopores and encapsulation efficiency is investigated in detail. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2089/2008/adma200700456_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Transient Hypothyroidism or Persistent Hyperthyrotropinemia in Neonates Born to Mothers with Excessive Iodine Intake (2004)

Perinatal exposure to excess iodine can lead to transient hypothyroidism in the newborn. In Japan, large quantities of iodine-rich seaweed such as kombu (Laminaria japonica) are consumed. However, effects of iodine from food consumed during the perinatal period are unknown. The concentration of iodine in serum, urine, and breast milk in addition to thyrotropin (TSH), free thyroxine (FT(4)), and thyroglobulin was measured in 34 infants who were positive at congenital hypothyroidism screening. Based on the concentration of iodine in the urine, 15 infants were diagnosed with hyperthyrotropinemia caused by the excess ingestion of iodine by their mothers during their pregnancy. According to serum iodine concentrations, these infants were classified into group A (over 17 microg/dL) and group B (under 17 microg/dL) of serum iodine. During their pregnancies these mothers consumed kombu, other seaweeds, and instant kombu soups containing a high level of iodine. It was calculated that the mothers of group A infants ingested approximately 2300-3200 microg of iodine, and the mothers of group B infants approximately 820-1400 microg of iodine per day during their pregnancies. Twelve of 15 infants have required levo-thyroxine (LT(4)) because hypothyroxinemia or persistent hyperthyrotropinemia was present. In addition, consumption of iodine by the postnatal child and susceptibility to the inhibitory effect of iodine may contribute in part to the persistent hyperthyrotropinemia. We propose that hyperthyrotropinemia related to excessive iodine ingestion by the mother during pregnancy in some cases may not be transient.
Phosphonate Ester Synthesis Using a Modified Mitsunobu Condensation (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhosphonate Ester Synthesis Using a Modified Mitsunobu CondensationDavid A. Campbell and Jason C. BermakCite this: J. Org. Chem. 1994, 59, 3, 658–660Publication Date (Print):February 1, 1994Publication History Published online1 May 2002Published inissue 1 February 1994https://pubs.acs.org/doi/10.1021/jo00082a027https://doi.org/10.1021/jo00082a027research-articleACS PublicationsRequest reuse permissionsArticle Views1613Altmetric-Citations62LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Immunomodulatory therapy for severe influenza (2011)

Influenza A virus is a significant cause of morbidity and mortality worldwide. Severe influenza is recognized as a clinical syndrome, characterized by hyperinduction of proinflammatory cytokine production, otherwise known as hypercytokinemia or a 'cytokine storm'. Research focused on therapeutics to modulate influenza virus-induced inflammation is currently underway. In this review, we discuss the limitations of current antiviral drug treatment strategies, describe the influenza viral and host pathogenicity determinants, and present the evidence supporting the use of immunomodulatory therapy to target the host inflammatory response as a means to improve clinical outcome in severe influenza. We then review the experimental data on investigational immunomodulatory agents targeting the host inflammatory response in severe influenza, including anti-TNF therapy, statins, glucocorticoids, cyclooxygenase-2 inhibitors, macrolides, peroxisome proliferator-activated receptor agonists, AMP-activated protein kinase agonists and high mobility group box 1 antagonists. We then conclude with a rationale for the use of mesenchymal stromal (stem) cells and angiopoietin-1 therapy against deleterious influenza-induced host responses that mediate end-organ injury and dysfunction.
Solving Polynomial Systems for the Kinematic Analysis and Synthesis of Mechanisms and Robot Manipulators (1995)

Problems in mechanisms analysis and synthesis and robotics lead naturally to systems of polynomial equations. This paper reviews the state of the art in the solution of such systems of equations. Three well-known methods for solving systems of polynomial equations, viz., Dialytic Elimination, Polynomial Continuation, and Grobner bases are reviewed. The methods are illustrated by means of simple examples. We also review important kinematic analysis and synthesis problems and their solutions using these mathematical procedures.
Formation of a bispecific antibody by the use of leucine zippers (1992)

A new method is described for the production of bispecific F(ab')2 heterodimers using leucine zippers. Two heterodimer-forming "zipper" peptides derived from the Fos and Jun proteins were respectively linked to the Fab' portions of two different mAb by gene fusion. The antibodies used were 145-2C11, which binds to murine CD3, and anti-Tac, which binds to the p55 chain of the human IL-2R. Anti-Tac Fab'-Jun and anti-CD3 Fab'-Fos were expressed individually as F(ab'-zipper)2 homodimers in the mouse myeloma cell line Sp2/0. When these homodimers were reduced at the hinge region to form monomers and then reoxidized together, the resulting end products were mostly F(ab'-zipper)2 heterodimers. Bispecific anti-CD3 x anti-Tac F(ab'-zipper)2 heterodimers produced by this method were shown to be highly effective in recruiting cytotoxic T cells to lyse IL-2R-bearing HuT-102 cells in vitro.
[The clinico-immunological characteristics and treatment of an intestinal infection of Klebsiella etiology]. (1995)

The examination of 265 patients with the diagnosis of acute enteric infection (AEI) of Klebsiella revealed that the disease took a mild course in 40%, a moderate course in 45.3% and a severe course in 14.7% of the patients. The clinical syndromes of acute gastritis, gastroenteritis, enteritis were observed; in cases of the severe course of AEI the hemolytic [correction of hemocolitic] syndrome was present. Immune shifts were characterized by T lymphopenia, a decrease in the number of T helpers/inductors (CD 4), the immunoregulatory indices (CD 4/CD 8), an increase in the level of circulating immune complexes. These levels reached their maximum in case of the severe course of Klebsiella infection and were retained till the patient was discharged from the hospital and, if any concomitant pathology was present, even for 1-3 months after discharge.
Eukaryotic Pyruvate Formate Lyase and Its Activating Enzyme Were Acquired Laterally from a Firmicute (2011)

Most of the major groups of eukaryotes have microbial representatives that thrive in low oxygen conditions. Those that have been studied in detail generate ATP via pathways involving anaerobically functioning enzymes of pyruvate catabolism that are typically absent in aerobic eukaryotes and whose origins remain controversial. These enzymes include pyruvate:ferredoxin oxidoreductase, pyruvate:NADP(+) oxidoreductase, and pyruvate formate lyase (Pfl). Pfl catalyzes the nonoxidative generation of formate and acetyl-Coenzyme A (CoA) from pyruvate and CoA and is activated by Pfl activating enzyme (Pfla). Within eukaryotes, this extremely oxygen-sensitive pathway was first described in the hydrogenosomes of anaerobic chytrid fungi and has more recently been characterized in the mitochondria and chloroplasts of the chlorophyte alga Chlamydomonas reinhardtii. To clarify the origins of this pathway, we have comprehensively searched for homologs of Pfl and Pfla in publicly available large-scale eukaryotic genomic and cDNA sequencing data, including our own from the anaerobic amoebozoan Mastigamoeba balamuthi. Surprisingly, we find that these enzymes are widely distributed and are present in diverse facultative or obligate anaerobic eukaryotic representatives of the archaeplastidan, metazoan, amoebozoan, and haptophyte lineages. Using maximum likelihood and Bayesian phylogenetic methods, we show that the eukaryotic Pfl and Pfla sequences each form monophyletic groups that are most closely related to homologs in firmicute gram-positive bacteria. Topology tests exclude both α-proteobacterial and cyanobacterial affinities for these genes suggesting that neither originated from the endosymbiotic ancestors of mitochondria or chloroplasts. Furthermore, the topologies of the eukaryote portion of the Pfl and Pfla trees significantly differ from well-accepted eukaryote relationships. Collectively, these results indicate that the Pfl pathway was first acquired by lateral gene transfer into a eukaryotic lineage most probably from a firmicute bacterial lineage and that it has since been spread across diverse eukaryotic groups by more recent eukaryote-to-eukaryote transfer events.
The Drg-1 gene suppresses tumor metastasis in prostate cancer. (2003)

Drg-1 was previously identified (N. van Belzen et al., Lab. Investig., 77: 85-92, 1997) as a gene that was up-regulated by the induction of differentiation in a colon carcinoma cell line in vitro. Subsequently, this gene was found to be regulated by several factors including hypoxia, androgen, p53, and N-myc. Recently, Drg-1 has also been shown to be involved in tumor progression in animals, although the clinical significance of its involvement remains to be investigated. To clarify the functional role of Drg-1 in prostate cancer, we examined a clinical archive of cancer specimens for the expression of Drg-1 by immunohistochemistry. We found that the expression of Drg-1 had a significant inverse correlation with the Gleason grading and the overall survival rate of patients. In particular, the gene expression in patients with lymph node or bone metastasis was significantly reduced as compared with those with localized prostate cancer, suggesting that the function of Drg-1 is negatively involved in metastatic progression of the disease. To further clarify the function of this gene in the advancement of prostate cancer, a spontaneous metastasis assay was performed in a severe combined immunodeficient (SCID) mouse model. We found that Drg-1 almost completely inhibited lung colonization of highly metastatic prostate cancer cells without affecting the growth of the primary tumors. These results strongly suggest that Drg-1 is a candidate metastasis suppressor gene for prostate cancer and may serve as a useful prognostic marker.