gebhart/patrepeval huggingface dataset:
Abstract B91: Induction of RXR transcriptional activity and consequent upregulation of p21 by 3-amino-6-(3-aminopropyl)-5,6-dihydro-5, 11-dioxo-11<i>H</i>-indeno[1,2-<i>c</i>]isoquinoline dihydrochloride in MCF-7 breast cancer cells (2010)

Abstract Retinoid X receptor (RXR) is known to play various roles in embryogenesis, metabolic processes, differentiation, and apoptosis. Recently, RXR has been studied as a target for cancer chemoprevention and treatment. To discover potential cancer chemopreventive agents acting through RXRs, we developed a cell line-based RXR response element (RXRE)-luciferase reporter gene assay system. Following extensive screening, 3-amino-6-(3aminopropyl)-5,6-dihydro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline dihydrochloride (AM6-36) was found to induce RXRE-luciferase activities in a dose-dependent manner. Subsequently, the substance was found to inhibit the proliferation of MCF-7 breast cancer cells in a concentration-dependent manner. Prompted by these results, we examined the underlying mechanism of AM6-36 anti-proliferative activity using MCF-cells as a model. In brief, at lower concentrations, G2/M arrest was observed, and S phase arrest was enhanced at higher concentrations. Based on DNA microarray analysis, AM6-36 was found to up-regulate the expression of CDKN1A, a target gene of RXR, by ∼40-fold. In accordance with this response, the protein level of CDKN1A (p21WAF1/CIP1) was increased in the presence of AM6-36. Induction of p21 by AM6-36 was abrogated following transient transfection of RXR siRNA, demonstrating the effect of AM6-36 on the expression of p21 is closely related to modulation of RXR transcriptional activity. These data suggest AM6-36 is a promising lead compound for the treatment or prevention of breast cancer. A synthetic procedure has been devised for large-scale production, moderate absorption and slow metabolism has been demonstrated with rats (p.o. administration), and more advanced anti-tumor evaluation is underway. (Supported by program project P01 CA48112 awarded by the National Cancer Institute.) Citation Information: Cancer Prev Res 2010;3(1 Suppl):B91.
Metabolic reprogramming, cell fate decision and non-coding RNA in tumor-initiating stem-like cells (2018)

Stem cell markers such as Nanog have been implicated in various cancer, but whether they are functionally contributing to cancer pathogenesis has remained unclear. Tumor-initiating stem-like cells (TICs) were isolated from mouse hepatocellular carcinoma (HCC) and human HCC patients. Using knowledge gained from the oncogenic signaling of TICs, we addressed new mechanistic hypotheses based on the novel discovery that the pluripotent transcription factor, NANOG, can reprogram the metabolism of HCC-derived TICs. These studies will motivate novel strategies for targeting and removing TICs and suggest new avenues to treat malignancies associated with human HCV and alcoholism and/or obesity. We determined novel targets of NANOG in TICs from patient and mouse models of HCC using genome-wide NANOG-binding site analysis (ChIP-seq) and how Nanog is regulated at the transcriptional to promote oncogenesis and self-renewal in TICs. NANOG-mediated metabolic reprogramming through suppression of mitochondria function in both experimental and clinical HCC downstream of TLR4/NANOG generates TICs and drives liver tumorigenesis. The p53 tumor suppressor acts as a barrier against stem cell proliferation, and inactivation of p53, or its stabilizing partner NUMB (cell fate decision molecule), leads to expansion of TICs. Although treatment efficacy of HCV has been dramatically improved in recent years, the incidence of HCV-associated HCC keeps rising due to the prevalence of obesity, alcoholism and illicit drug usage in HCV patients. RNA-binding protein MSI2 is elevated in several cancers and is linked to poor prognosis. We also performed RIP-seq using anti-MSI2 antibody in TICs and subsequent validation by qPCR analysis. Among the MSI2-bound RNAs, MYC mRNA and long noncoding RNA (LncRNA) were identified by RIP-qPCR analysis. MSI2 promotes liver tumorigenesis by maintenance of MYC expression by inhibition of LncRNA processing. This newly discovered mechanistic framework for TIC proliferation represents a key innovation and holds significant potential as a therapeutic target.
Supplementary Table S14 from C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in &lt;i&gt;FLT3&lt;/i&gt;-Mutant Leukemia (2023)

&lt;p&gt;Table S14: PUFA/MUFA ratios in phospholipids&lt;/p&gt;
Proteinase 3-processed form of the recombinant IL-32 separate domain (2008)

Interleukin-32 (IL-32) induces a variety of proinflammatory cytokines and chemokines. The IL-32 transcript was reported originally in activated T cells; subsequently, it was demonstrated to be abundantly expressed in epithelial and endothelial cells upon stimulation with inflammatory cytokines. IL-32 is regulated robustly by other major proinflammatory cytokines, thereby suggesting that IL-32 is crucial to inflammation and immune responses. Recently, an IL-32alpha-affinity column was employed in order to isolate an IL-32 binding protein, neutrophil proteinase 3 (PR3). Proteinase 3 processes a variety of inflammatory cytokines, including TNFalpha, IL-1beta, IL-8, and IL-32, thereby enhancing their biological activities. In the current study, we designed four PR3-cleaved IL-32 separate domains, identified by potential PR3 cleavage sites in the IL-32alpha and gamma polypeptides. The separate domains of the IL-32 isoforms alpha and gamma were more active than the intrinsic alpha and gamma isoforms. Interestingly, the N-terminal IL-32 isoform gamma separate domain evidenced the highest levels of biological activity among the IL-32 separate domains.
Sphingolipid-based drugs selectively kill cancer cells by down-regulating nutrient transporter proteins (2011)

Cancer cells are hypersensitive to nutrient limitation because oncogenes constitutively drive glycolytic and TCA (tricarboxylic acid) cycle intermediates into biosynthetic pathways. As the anaplerotic reactions that replace these intermediates are fueled by imported nutrients, the cancer cell's ability to generate ATP becomes compromised under nutrient-limiting conditions. In addition, most cancer cells have defects in autophagy, the catabolic process that provides nutrients from internal sources when external nutrients are unavailable. Normal cells, in contrast, can adapt to the nutrient stress that kills cancer cells by becoming quiescent and catabolic. In the present study we show that FTY720, a water-soluble sphingolipid drug that is effective in many animal cancer models, selectively starves cancer cells to death by down-regulating nutrient transporter proteins. Consistent with a bioenergetic mechanism of action, FTY720 induced homoeostatic autophagy. Cells were protected from FTY720 by cell-permeant nutrients or by reducing nutrient demand, but blocking apoptosis was ineffective. Importantly, AAL-149, a FTY720 analogue that lacks FTY720's dose-limiting toxicity, also triggered transporter loss and killed patient-derived leukaemias while sparing cells isolated from normal donors. As they target the metabolic profile of cancer cells rather than specific oncogenic mutations, FTY720 analogues such as AAL-149 should be effective against many different tumour types, particularly in combination with drugs that inhibit autophagy.
Molecular characterization of a human immunoglobulin G4 antibody specific for the major birch pollen allergen, Bet v 1 (2007)

Our study demonstrates that not all allergen-specific IgG antibodies inhibit IgE recognition of allergens and can contribute to the success of immunotherapy. The epitope specificity and affinity of IgG antibodies but not their isotype are decisive for their protective activity.
Multiple Allelic Deletions and Intratumoral Genetic Heterogeneity in MEN1 Pancreatic Tumors<sup>1</sup> (2001)

Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome with multiple tumors of the endocrine pancreas, the parathyroid, the pituitary, and other tissues. The MEN1 gene at 11q13 is homozygously mutated in the majority of MEN1 tumors. Here we present a genome-wide loss of heterozygosity (LOH) screening of 23 pancreatic lesions, one duodenal tumor, and one thymic carcinoid from 13 MEN1 patients. Multiple allelic deletions were found. Fractional allelic loss varied from 6-75%, mean 31%. All pancreatic tumors displayed LOH on chromosome 11, whereas the frequency of losses for chromosomes 3, 6, 8, 10, 18, and 21 was over 30%. Different lesions from individual patients had discrepant patterns of LOH. Intratumoral heterogeneity was revealed, with chromosome 6 and 11 deletions in most tumor cells, whereas other chromosomal loci were deleted in portions of the analyzed tumor. Chromosome 6 deletions were mainly found in lesions from patients with malignant features. Fractional allelic loss did not correlate to malignancy or to tumor size. Our findings indicate that MEN1 pancreatic tumors fail to maintain DNA integrity and demonstrate signs of chromosomal instability.
Brain-derived neurotrophic factor and inflammatory markers in patients with early- vs. late-stage bipolar disorder (2008)

Bipolar I disorder (BD) has a poorer longer-term outcome than previously thought, with persistent cognitive impairment and functional decline. The neurobiological underpinnings that might underlie these changes remain unknown. Changes in brain-derived neurotrophic factor (BDNF) levels and cytokines are potential candidates. The aim of this study was to examine both cytokine and BDNF levels and their relationship in BD patients in the early and late stages of the disorder. We measured serum BDNF, TNF-alpha, IL-6 and IL-10 levels in a total of 60 patients with BD I and we compared those in early stages of illness with those in late stages of illness and also compared both groups with 60 matched healthy controls. BDNF was decreased only in those patients in the late stage of bipolar disorder. Moreover, BDNF levels were negatively correlated with length of illness. In contrast, all interleukins and TNF-alpha were increased in the early stages of BD, compared to controls. While TNF-alpha and IL-6 continued to be significantly higher than controls at late stages of BD, IL-10 did not. When levels were compared between patients at early and late stages of illness, there was a significant decrease in BDNF and IL-6 in the later stage of BD compared to the early stage. Inversely, TNF-alpha showed a significant increase at the later stage. Failure of inflammatory defences in the late stage of the disorder may account for reduction in BDNF and continued elevations in cytokines; thus these may have the potential to serve as markers of illness progression in BD.
Review article: Comparison of local particle filters and new implementations (2018)

Abstract. Particle filtering is a generic weighted ensemble data assimilation method based on sequential importance sampling, suited for nonlinear and non-Gaussian filtering problems. Unless the number of ensemble members scales exponentially with the problem size, particle filter (PF) algorithms experience weight degeneracy. This phenomenon is a manifestation of the curse of dimensionality that prevents the use of PF methods for high-dimensional data assimilation. The use of local analyses to counteract the curse of dimensionality was suggested early in the development of PF algorithms. However, implementing localisation in the PF is a challenge, because there is no simple and yet consistent way of gluing together locally updated particles across domains. In this article, we review the ideas related to localisation and the PF in the geosciences. We introduce a generic and theoretical classification of local particle filter (LPF) algorithms, with an emphasis on the advantages and drawbacks of each category. Alongside the classification, we suggest practical solutions to the difficulties of local particle filtering, which lead to new implementations and improvements in the design of LPF algorithms. The LPF algorithms are systematically tested and compared using twin experiments with the one-dimensional Lorenz 40-variables model and with a two-dimensional barotropic vorticity model. The results illustrate the advantages of using the optimal transport theory to design the local analysis. With reasonable ensemble sizes, the best LPF algorithms yield data assimilation scores comparable to those of typical ensemble Kalman filter algorithms, even for a mildly nonlinear system.
Comparison of shoot regeneration potential from seedling explants of Australian cauliflower ( <i>Brassica oleracea</i> var. <i>botrytis</i> ) varieties (1998)

Genetic engineering of crop plants relies on the development of efficient methods for the regeneration of viable shoots from cultured tissues. The objective of the present study was to develop a protocol for efficient shoot and plant regeneration from seedling explants of commercial cauliflower ( B. oleracea var. botrytis ) genotypes and to compare the regeneration capacity of the most commonly used explants: cotyledon, hypocotyl, and root. A combination of growth hormones including 6-benzylaminopurine, 1-naphthylacetic acid, and gibberellic acid was used in the MS-based medium, and factors influencing regeneration of shoots were investigated. Using the protocol described here, shoots from hypocotyl, cotyledon, and root explants of all the 11 genotypes tested were able to be regenerated. Root and hypocotyl explants produced more callus than cotyledon explants and also were more responsive to shoot regeneration, as a high percentage (&amp;gt;71% and &amp;gt;80% for hypocotyl and roots, respectively) of shoot initiation from these explants was observed. In addition, root and hypocotyl explants also produced more shoots per explant than cotyledon explants. The in vitro regenerated shoots were successfully rooted and acclimatised to glasshouse conditions. This study shows that seedling explants of cauliflower are amenable to multiple shoot formation with high regeneration frequencies, and could be used for genetic transformation experiments.
Monoclonal antibodies to Legionella Mip proteins recognize genus- and species-specific epitopes (1995)

Monoclonal antibodies (MAbs) against the virulence-associated Mip protein of Legionella spp. were raised by immunizing BALB/c mice with (i) Legionella pneumophila, (ii) Legionella micdadei, and (iii) purified recombinant native Mip protein cloned from L. pneumophila Philadelphia 1. Following screening of seeded wells by immunoblot analysis with homologous antigens, eight Mip-specific MAbs were found. These MAbs were chosen to investigate the antigenic diversity of Mip proteins in the genus Legionella. Mip was detected in 82 Legionella strains representing all 34 species tested. One of these MAbs, obtained from immunization with L. micdadei, recognized an epitope common to all Legionella species tested by immunoblot analysis. Another MAb was discovered to be specific for the Mip protein of L. pneumophila. The remaining six MAbs recognized 18 to 79% of Legionella species included in this study. By making use of the MAbs introduced in this study, it could be shown that, based on Mip protein epitope expression, Legionella species can be divided into at least six antigenetically distinct groups. As demonstrated by 43 L. pneumophila strains representing all serogroups, no antigenic diversity of Mip proteins was found for this species. In addition, 18 non-Legionella species, including Chlamydia trachomatis, Neisseria meningitidis, Pseudomonas aeruginosa, and Saccharomyces cerevisiae, all of which are known to carry genes homologous to the Legionella mip genes, were reacted against all eight MAbs. No cross-reactivity was detectable in any of those strains.
The EpiOcular™ Eye Irritation Test is the Method of Choice for the <i>In Vitro</i> Eye Irritation Testing of Agrochemical Formulations: Correlation Analysis of EpiOcular Eye Irritation Test and BCOP Test Data According to the UN GHS, US EPA and Brazil ANVISA Classification Schemes (2015)

The Bovine Corneal Opacity and Permeability (BCOP) test is commonly used for the identification of severe ocular irritants (GHS Category 1), but it is not recommended for the identification of ocular irritants (GHS Category 2). The incorporation of human reconstructed tissue model-based tests into a tiered test strategy to identify ocular non-irritants and replace the Draize rabbit eye irritation test has been suggested (OECD TG 405). The value of the EpiOcular™ Eye Irritation Test (EIT) for the prediction of ocular non-irritants (GHS No Category) has been demonstrated, and an OECD Test Guideline (TG) was drafted in 2014. The purpose of this study was to evaluate whether the BCOP test, in conjunction with corneal histopathology (as suggested for the evaluation of the depth of the injury( and/or the EpiOcular-EIT, could be used to predict the eye irritation potential of agrochemical formulations according to the UN GHS, US EPA and Brazil ANVISA classification schemes. We have assessed opacity, permeability and histopathology in the BCOP assay, and relative tissue viability in the EpiOcular-EIT, for 97 agrochemical formulations with available in vivo eye irritation data. By using the OECD TG 437 protocol for liquids, the BCOP test did not result in sufficient correct predictions of severe ocular irritants for any of the three classification schemes. The lack of sensitivity could be improved somewhat by the inclusion of corneal histopathology, but the relative viability in the EpiOcular-EIT clearly outperformed the BCOP test for all three classification schemes. The predictive capacity of the EpiOcular-EIT for ocular non-irritants (UN GHS No Category) for the 97 agrochemical formulations tested (91% sensitivity, 72% specificity and 82% accuracy for UN GHS classification) was comparable to that obtained in the formal validation exercise underlying the OECD draft TG. We therefore conclude that the EpiOcular-EIT is currently the best in vitro method for the prediction of the eye irritation potential of liquid agrochemical formulations.
Visual QC Protocol for FreeSurfer Cortical Parcellations from Anatomical MRI (2020)

Abstract Quality control of morphometric neuroimaging data is essential to improve reproducibility. Owing to the complexity of neuroimaging data and subsequently the interpretation of their results, visual inspection by trained raters is the most reliable way to perform quality control. Here, we present a protocol for visual quality control of the anatomical accuracy of FreeSurfer parcellations, based on an easy-to-use open source tool called VisualQC. We comprehensively evaluate its utility in terms of error detection rate and inter-rater reliability on two large multi-site datasets, and discuss site differences in error patterns. This evaluation shows that VisualQC is a practically viable protocol for community adoption.
Women, Marriage and Property in Wealthy Landed Families in Ireland, 1750–1850 (2005)

Restricted accessAbstractFirst published July 2005Women, Marriage and Property in Wealthy Landed Families in Ireland, 1750–1850: Ph.D. Thesis, Queen's University, Belfast, 2004Deborah WilsonView all authors and affiliationsVolume 32, Issue 1https://doi.org/10.1177/033248930503200108
Characterization of DLC-A and DLC-B, two families of cytoplasmic dynein light chain subunits. (1994)

Cytoplasmic dynein is a minus-end-directed, microtubule-dependent motor composed of two heavy chains (approximately 530 kDa), three intermediate chains (approximately 74 kDa), and a family of approximately 52-61 kDa light chains. Although the approximately 530 kDa subunit contains the motor and microtubule binding domains of the complex, the functions of the smaller subunits are not known. Using two-dimensional gel electrophoresis and proteolytic mapping, we show here that the light chains are composed of two major families, a higher M(r) family (58, 59, 61 kDa; dynein light chain group A [DLC-A]) and lower M(r) family (52, 53, 55, 56 kDa; dynein light chain group B [DLC-B]). Dissociation of the cytoplasmic dynein complex with potassium iodide reveals that all light chain polypeptides are tightly associated with the approximately 530 kDa heavy chain, whereas the approximately 74 kDa intermediate chain polypeptides are more readily extracted. Treatment with alkaline phosphatase alters the mobility of four of the light chain polypeptides, indicating that these subunits are phosphorylated. Sequencing of a cDNA clone encoding one member of the DLC-A family reveals a predicted globular structure that is not homologous to any known protein but does contain numerous potential phosphorylation sites and a consensus nucleotide-binding motif.
Effect of “X” Ligands on the Photocatalytic Reduction of CO<sub>2</sub> to CO with Re(pyridylNHC‐CF<sub>3</sub>)(CO)<sub>3</sub>X Complexes (2020)

A series of five Re(pyNHC‐aryl)(CO) 3 X complexes varying the “X” ligand where pyNHC is a pyridyl N‐heterocyclic carbene have been synthesized and characterized through NMR, UV/Vis absorption spectroscopy, IR, mass spectrometry, time‐correlated single photon counting, computational analysis, and cyclic voltammetry. The photocatalytic reduction of CO 2 to CO in the presence of a sacrificial electron donor with these complexes is evaluated using a simulated solar spectrum (AM 1.5G). Comparison of Br and CH 3 CN as the “X” ligand shows the same photocatalytic activity (both 32 TON). The use of Cl, NCS and P(OEt) 3 “X” ligands all led to diminished reactivity with as little as 2 TON for the P(OEt) 3 complex. These results were rationalized through computational analysis of “X” dissociation and excited‐state lifetime measurements. These results highlight the importance of the “X” ligand selection on catalysis with Re‐pyNHC complexes.
The importance of the subepithelial resistance for the electrical properties of the rat jejunum <i>in vitro</i> (1988)

The aim of the study was to evaluate full-thickness and partially stripped jejunum as a model for neurogenic control of electrogenic ion transport. The electrical properties of full-thickness and partially stripped segments were studied in Ussing chambers. Using square-pulse analysis, subepithelial and epithelial resistances (Rs and Rp) were determined, and by compensating for the potential fall across Rs, the current generated by the epithelium could be measured. In full-thickness tissue, Rs was approximately 80% of total tissue resistance, and the current measured during short-circuiting of the whole tissue (SCC) was therefore only 20-25% of the current generated by the epithelium (Im). Surgical stripping of the tissue decreased Rs by 10-20%. This means that in full thickness as well as in stripped tissue, 70-80% of the potential difference across the epithelial layer remains after traditional 'short circuiting'. Over a 25-min period, none of the electrical parameters changed significantly in the full-thickness tissues. In the stripped group PD, SCC and Im fell significantly, and in parallel during the same period of time. Neither glucose, noradrenaline, met-enkephalin or carbachol had any significant effect on Rs, Rp or the Rs/Rp ratio. The relative effects of these agents on Im and SCC were therefore similar. Substance P and VIP increased the Rs/Rp ratio significantly and, therefore, the effect of these drugs on Im was significantly more pronounced than the effect on SCC. The results show that the subepithelial resistance must be taken into account when the electrogenic activity in the epithelium is to be determined correctly. Conventionally measured SCC reflects the electrogenic effect of the tested putative neurotransmitters, but the magnitude of the responses is grossly underestimated, particularly for substance P and VIP.