gebhart/patrepeval huggingface dataset:
Protection by pioglitazone in the MPTP model of Parkinson's disease correlates with IκBα induction and block of NFκB and iNOS activation (2003)

Inflammation has been implicated in the pathogenesis of Parkinson's disease (PD). In the chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD, inducible NO synthase (iNOS) derived nitric oxide (NO) is an important mediator of dopaminergic cell death. Ligands of the peroxisome proliferator-activated receptor (PPAR) exert anti-inflammatory effects. We here investigated whether pioglitazone, a PPARgamma agonist, protected mice from MPTP-induced dopaminergic cell loss, glial activation, and loss of catecholamines in the striatum. As shown by western blot, PPARgamma was expressed in the striatum and the substantia nigra of vehicle- and MPTP-treated mice. Oral administration of 20 mg/(kg day) of pioglitazone protected tyrosine hydroxylase (TH)-positive substantia nigra neurons from death induced by 5 x 30 mg/kg MPTP. However, the decrease of dopamine in the striatum was only partially prevented. In mice treated with pioglitazone, there were a reduced activation of microglia, reduced induction of iNOS-positive cells and less glial fibrillary acidic protein positive cells in both striatum and substantia nigra pars compacta. In addition, treatment with pioglitazone almost completely blocked staining of TH-positive neurons for nitrotyrosine, a marker of NO-mediated cell damage. Because an increase in inhibitory protein-kappa-Balpha (IkappaBalpha) expression and inhibition of translocation of the nuclear factor kappaB (NFkappaB) subunit p65 to the nucleus in dopaminergic neurons, glial cells and astrocytes correlated with the protective effects of pioglitazone, our results suggest that pioglitazone sequentially acts through PPARgamma activation, IkappaBalpha induction, block of NFkappaB activation, iNOS induction and NO-mediated toxicity. In conclusion, treatment with pioglitazone may offer a treatment opportunity in PD to slow the progression of disease that is mediated by inflammation.
Histone deacetylation is directly involved in desilencing the expression of the catalytic subunit of telomerase in normal lung fibroblast (2005)

The regulation of telomerase expression in normal cells is poorly understood. Moreover, the molecular mechanism underlying tumor-specific expression of telomerase remains unclear. We investigated the link between histone deacetylation and telomerase activity in normal lung and lung tumor cells. Four non-small-cell lung cancer (NSCLC) lines and one normal lung fibroblast line were tested for telomerase activity with or without Trichostatin A(TSA). The telomerase activity and the expression of telomerase associated components were determined by TRAP assay, RT-PCR analysis and Western blot analysis. All 4 NSCLC cell lines exposed to 1 microM TSA for 24 h had no change in telomerase activity or hTERT mRNA level. Telomerase activity was very low in normal lung fibroblasts (mrc-9) until exposed to 1 microM TSA for 24 h, at which time telomerase activity was readily detectable, with concomitant upregulation of hTERT mRNA (10-fold). The level of other telomerase associated components (hTER and TP1) were unaltered. Furthermore, 1 microM TSA exposure for 24 h did not alter the level of c-Myc or p21 mRNA. Immunodetection reveled that hTERT protein expression increased (approximately 6 fold) compared to c-Myc, p21, or gelsolin. The effect of TSA on hTERT expression is independent of DNA methylation as judged by 5-azacytidine (5aza) treatment. TSA effect on mrc-9 cells is unaltered even in the presence of 200 microg/ml cyclohexamide, suggesting a direct inhibition of histone deacetylation. Collectively, our study indicates that inhibition of histone deacetylation selectively regulates the transcriptional derepression of telomerase catalytic subunit in normal lung fibroblast cells compared to lung tumor cells.
An Eye Model for Practicing Vitreoretinal Membrane Peeling (2006)

A cost-effective, reusable practice eye model for epiretinal membrane peeling that uses easily obtained, commercially available materials was developed. A commercially available globe that is anatomically and optically similar to the human eye was modified by creating 2 ports that simulate superior sclerotomies. The model has a removable plastic anterior segment, which allows access to the posterior segment for practice membrane placement. Membranes were created on the macula by applying a coat of liquid skin bandage. Membrane peeling was performed under an ophthalmic operating microscope using a disposable flat vitrectomy lens. The basic skills required for membrane peeling can be demonstrated and acquired by practicing with this eye model. The practice eye model is expected to enhance the acquisition of skills required for epiretinal membrane peeling.
Granulocyte-macrophage colony-stimulating factor reactivates fetal hemoglobin synthesis in erythroblast clones from normal adults (1989)

Reactivation of fetal hemoglobin (HbF, alpha 2 gamma 2) synthesis was previously reported in normal human adult erythroblast colonies (“bursts”) generated by erythroid progenitors (BFU-E) in fetal calf serum-supplemented (FCS+) semisolid cultures stimulated with erythropoietin (Ep). Our studies focused on the reactivation of HbF synthesis in normal adult erythroid bursts generated by peripheral blood mononuclear cells (PBMCs) seeded in FCS+ methylcellulose culture. Reactivation is almost totally suppressed when (a) PBMCs are grown in optimized FCS- culture, or (b) PBMCs are first stringently depleted of monocytes and then plated in FCS+ medium (ie, BFU-E growth in FCS+ Mo- culture). In both experimental conditions, the proliferation of lymphocytes and macrophages interspersed among colonies is drastically reduced, and the cloning efficiency of granulocyte-macrophage (GM) progenitors is sharply diminished. In either case, addition of biosynthetic GM colony-stimulating factor (GM-CSF) induces a dose- related increase of HbF synthesis up to the level in FCS+ culture, with even more elevated values on delayed addition of Ep. A dose-related increase was also observed in erythroblast clones generated by highly purified BFU-E. These results suggest that reactivation of HbF synthesis in normal adults is at least in part mediated by GM-CSF. Furthermore, they imply intriguing hypotheses on the mechanism(s) of perinatal Hb switching. Finally, they raise the possibility of reactivation of HbF synthesis in beta-thalassemia and sickle cell anemia by GM-CSF therapy.
The Quest for Ground Truth in Musical Artist Similarity (2002)

It would be interesting and valuable to devise an automatic measure of the similarity between two musicians based only on an analysis of their recordings. To develop such a measure, however, presupposes some 'ground truth' training data describing the actual similarity between certain pairs of artists that constitute the desired output of the measure. Since artist similarity is wholly subjective, such data is not easily obtained. In this paper, we describe several attempts to construct a full matrix of similarity measures between a set of some 400 popular artists by regularizing limited subjective judgment data. We also detail our attempts to evaluate these measures by comparison with direct subjective similarity judgments collected via a web-based survey in April 2002. Overall, we find that subjective artist similarities are quite variable between users—casting doubt on the concept of a single 'ground truth'. Our best measure, however, gives reasonable agreement with the subjective data, and forms a useable stand-in. In addition, our evaluation methodology may be useful for comparing other measures of artist similarity.
Visualization of Surfactants on Nanostructured Palladium Clusters by a Combination of STM and High-Resolution TEM (1995)

Scanning tunneling microscopy (STM) and high-resolution transmission electron microscopy (TEM) have been used to determine the dimensions of a series of palladium clusters stabilized by tetraalkylammonium salts. Electrochemically prepared colloids were used in which the average diameter of the inner metal core was varied between 2 and 4 nanometers, and the size of the ammonium ions was adjusted in the series (+)N(n-C(4)H(9))(4) < (+)N(n-C(8)H(17))(4) < (+)N(n-C(18)H(37))(4). The difference between the mean diameter determined by STM and that measured by TEM allows the determination of the thickness of the protective surfactant layer. On the basis of these studies, a model of the geometric properties of ammonium-stabilized palladium clusters has been proposed. Suggestions for the mechanism of the STM imaging process are also made.
Jean-William Lapierre, Muriel Roy, Les Acadiens (1985)

George Pierre. Jean-William Lapierre, Muriel Roy, Les Acadiens. In: Annales de Géographie, t. 94, n°521, 1985. p. 122.
Design and Evaluation of Cyclodextrin-Based Drug Formulation (2004)

The pharmaceutically useful cyclodextrins (CyDs) are classified into hydrophilic, hydrophobic, and ionic derivatives. Because of the multi-functional characteristics and bioadaptability, these CyDs are capable of alleviating the undesirable properties of drug molecules through the formation of inclusion complexes or the form of CyD/drug conjugates. This review outlines the current application of CyDs in design and evaluation of CyD-based drug formulation, focusing on their ability to enhance the drug absorption across biological barriers, the ability to control the rate and time profiles of drug release, and the ability to deliver a drug to a targeted site.
The Mycobacterium tuberculosis Phagosome Is a HLA-I Processing Competent Organelle (2009)

Mycobacterium tuberculosis (Mtb) resides in a long-lived phagosomal compartment that resists maturation. The manner by which Mtb antigens are processed and presented on MHC Class I molecules is poorly understood. Using human dendritic cells and IFN-gamma release by CD8(+) T cell clones, we examined the processing and presentation pathway for two Mtb-derived antigens, each presented by a distinct HLA-I allele (HLA-Ia versus HLA-Ib). Presentation of both antigens is blocked by the retrotranslocation inhibitor exotoxin A. Inhibitor studies demonstrate that, after reaching the cytosol, both antigens require proteasomal degradation and TAP transport, but differ in the requirement for ER-golgi egress and new protein synthesis. Specifically, presentation by HLA-B8 but not HLA-E requires newly synthesized HLA-I and transport through the ER-golgi. Phenotypic analysis of the Mtb phagosome by flow organellometry revealed the presence of Class I and loading accessory molecules, including TAP and PDI. Furthermore, loaded HLA-I:peptide complexes are present within the Mtb phagosome, with a pronounced bias towards HLA-E:peptide complexes. In addition, protein analysis also reveals that HLA-E is enriched within the Mtb phagosome compared to HLA-A2. Together, these data suggest that the phagosome, through acquisition of ER-localized machinery and as a site of HLA-I loading, plays a vital role in the presentation of Mtb-derived antigens, similar to that described for presentation of latex bead-associated antigens. This is, to our knowledge, the first description of this presentation pathway for an intracellular pathogen. Moreover, these data suggest that HLA-E may play a unique role in the presentation of phagosomal antigens.
Toward a Quantitative Definition of Manual Lifting Postures (1997)

Manual lifting techniques are commonly defined in terms of the postures adopted at the start of the lift. Quantitative definition is problematic, however, because the absolute joint angles adopted to lift an object are influenced by task parameters, such as the initial height of the load. We present an argument for the use of a postural index (the ratio of knee flexion from normal standing to the sum of ankle, hip, and lumbar vertebral flexion) to define the postures adopted at the start of lifting. Stooped postures adopted at the start of a lift correspond to postural indices close to 0, whereas full squat postures correspond to postural indices close to 1. We use angular kinematic data gathered from 71 individuals lifting loads of varying mass from a range of starting heights to illustrate the utility of this index. Although average absolute joint angles were influenced by load mass and initial load height, the average postural index remained unchanged. For example, changes in starting height from 9 cm to 63 cm accounted for between 19% and 67% of the variance in joint positions at the start of the lift but only 1% of the variance in average postural index. This suggests that the postural index provides a method of defining lifting posture that is independent of specific joint positions.
The N-Terminal B-Domain of T4 Gene 32 Protein Modulates the Lifetime of Cooperatively Bound Gp32−ss Nucleic Acid Complexes (1996)

The N-terminal basic or B-domain (residues 1-21) of bacteriophage T4 gene 32 protein (gp32) provides a major determinant for highly cooperative binding by gp32 to single-stranded (ss) nucleic acids at equilibrium. In order to gain mechanistic insight into N-terminal domain function, the kinetics of dissociation of wild-type and previously characterized B-domain substitution mutant gp32s (R4K, R4Q, and K3A) from the model ribohomopolymer, poly(A), have been investigated under solution conditions identical to those used for equilibrium studies [Villemain, J. L., & Giedroc, D. P. (1993) Biochemistry 32, 11235-11246; Villemain, J. L., & Giedroc, D. P. (1996) J. Biol. Chem. 271, 27623-27629]. The dissociation of cooperatively bound gp32-poly(A) complexes was induced by sodium chloride concentration jumps and monitored by an increase in tryptophan fluorescence upon dissociation of the protein from poly(A) using stopped-flow techniques. The apparent dissociation rate constant, kd(app), for all mutant proteins studied was found to depend strongly on the initial fractional saturation of poly(A) just as was found previously for wild-type gp32. This permitted application of Lohman's model for the irreversible dissociation of cooperatively bound gp32-nucleic acid complexes [Lohman, T. M. (1983) Biopolymers 22, 1697-1713] from which the molecular rate constant, ke, the rate of dissociation of a protein monomer from teh end of a gp32-ss nucleic acid complex or protein cluster, could be determined. From the [NaCl]-dependence of kd(app), ke determined at 0.45 M NaCl, pH 8.1, 20 degrees C, was found to be 62 +/- 23, 78 +/- 8, 328 +/- 36, and 384 +/- 34 s-1 for wild-type, R4K, K3A, and R4Q gp32s, respectively. With the exception of R4K gp32, we find a striking correlation between the relative magnitudes of ke and Kapp, suggesting that the molecular defect in the equilibrium binding properties of the N-terminal domain mutants resides in the increased rate at which gp32 monomers dissociate from singly contiguous binding sites at the ends of clusters. The bimolecular association rate constant measured for wild-type gp32 and a weakly binding B-domain mutant, R4T gp32, to poly(dT) was found to be nearly identical, further evidence that the primary defect is in the dissociation reaction. We conclude that the N-terminal domain strongly modulates the lifetime of cooperatively bound gp32-polynucleotide complexes. The mechanistic and functional implications of these findings are discussed.
Requirement of the RNA Editing Deaminase ADAR1 Gene for Embryonic Erythropoiesis (2000)

The members of the ADAR (adenosine deaminase acting on RNA) gene family are involved in site-selective RNA editing that changes adenosine residues of target substrate RNAs to inosine. Analysis of staged chimeric mouse embryos with a high contribution from embryonic stem cells with a functional null allele for ADAR1 revealed a heterozygous embryonic-lethal phenotype. Most ADAR1+/- chimeric embryos died before embryonic day 14 with defects in the hematopoietic system. Our results suggest the importance of regulated levels of ADAR1 expression, which is critical for embryonic erythropoiesis in the liver.
Principles and Practice of Gynecologic Oncology (1992)

Epidemilogy of gynaecologic cancers genetics of gynaecologic cancer basic biology and biochemistry of gynaecologic cancer tumour invasion and metastases oncogenes and antioncogenes immunology of gynaecologic cancers tumour markers cancer prevention hormonal interactions in gynaecologic malignancies biostatistics and clinical trials surgery in gynaecologic oncology perioperative and critical care biologic and physical aspects of radiation oncology principles of chemotherapy in gynaecologic cancer pharmacology and therapeutics in gynaecologic cancer gynaecologic oncology for the general obstetrician gynaecologist cancer in the pregnant patient management of infections in gynaecologic cancer patients management of pain quality of life and psychosocial aspects of gynaecologic cancer care sexual rehabilitation - surgical and psychological approaches nutrition in gynaecologic cancer patients diagnostic imaging techniques in gynaecologic oncology management of late effects of treatment AIDS and women pathogenesis and diagnosis of preinvasive lesions of the lower genital tract vulva vagina uterine cervix corpus - epithelial tumours corpus - mesenchymal tumours epithelial ovarian cancer ovarian germ cell tumours stromal tumours of the ovary carcinoma of the fallopian tube gestational trophoblastic disease breast cancer.
Validation of the Emotiv EPOC ® EEG gaming system for measuring research quality auditory ERPs (2013)

Background. Auditory event-related potentials (ERPs) have proved useful in investigating the role of auditory processing in cognitive disorders such as developmental dyslexia, specific language impairment (SLI), attention deficit hyperactivity disorder (ADHD), schizophrenia, and autism. However, laboratory recordings of auditory ERPs can be lengthy, uncomfortable, or threatening for some participants - particularly children. Recently, a commercial gaming electroencephalography (EEG) system has been developed that is portable, inexpensive, and easy to set up. In this study we tested if auditory ERPs measured using a gaming EEG system (Emotiv EPOC(®), www.emotiv.com) were equivalent to those measured by a widely-used, laboratory-based, research EEG system (Neuroscan). Methods. We simultaneously recorded EEGs with the research and gaming EEG systems, whilst presenting 21 adults with 566 standard (1000 Hz) and 100 deviant (1200 Hz) tones under passive (non-attended) and active (attended) conditions. The onset of each tone was marked in the EEGs using a parallel port pulse (Neuroscan) or a stimulus-generated electrical pulse injected into the O1 and O2 channels (Emotiv EPOC(®)). These markers were used to calculate research and gaming EEG system late auditory ERPs (P1, N1, P2, N2, and P3 peaks) and the mismatch negativity (MMN) in active and passive listening conditions for each participant. Results. Analyses were restricted to frontal sites as these are most commonly reported in auditory ERP research. Intra-class correlations (ICCs) indicated that the morphology of the research and gaming EEG system late auditory ERP waveforms were similar across all participants, but that the research and gaming EEG system MMN waveforms were only similar for participants with non-noisy MMN waveforms (N = 11 out of 21). Peak amplitude and latency measures revealed no significant differences between the size or the timing of the auditory P1, N1, P2, N2, P3, and MMN peaks. Conclusions. Our findings suggest that the gaming EEG system may prove a valid alternative to laboratory ERP systems for recording reliable late auditory ERPs (P1, N1, P2, N2, and the P3) over the frontal cortices. In the future, the gaming EEG system may also prove useful for measuring less reliable ERPs, such as the MMN, if the reliability of such ERPs can be boosted to the same level as late auditory ERPs.
ROSeAnn (2013)

Named entity extractors can be used to enrich both text and Web documents with semantic annotations. While originally focused on a few standard entity types, the ecosystem of annotators is becoming increasingly diverse, with recognition capabilities ranging from generic to specialised entity types. Both the overlap and the diversity in annotator vocabularies motivate the need for managing and integrating semantic annotations: allowing users to see the results of multiple annotations and to merge them into a unified solution. We demonstrate ROSEANN, a system for the management of semantic annotations. ROSEANN provides users with a unified view over the opinion of multiple independent annotators both on text and Web documents. It allows users to understand and reconcile conflicts between annotations via ontology-aware aggregation. ROSEANN incorporates both supervised aggregation, appropriate when representative training data is available, and an unsupervised method based on the notion of weighted-repair.
Far-Red Radiation Reflected from Adjacent Leaves: An Early Signal of Competition in Plant Canopies (1990)

When individual seedlings of Datura ferox and Sinapis alba were transferred to populations formed by plants of similar stature, they responded with an increase in the rate of stem elongation. The reaction was detected within 3 days after transplanting and occurred well before shading among neighbors became important. This rapid response, which may be crucial for success in the competition for light, was reduced or abolished when individual internodes were "blinded" to the far-red radiation scattered by the surrounding seedlings. These results show the operation of a localized, photomorphogenetic control of stem elongation that may play a central role in the plastic adjustment of plants during the early stages of canopy development.
Mutagenic Stabilization and/or Disruption of a CD4-Bound State Reveals Distinct Conformations of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein (2002)

The human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein is conformationally flexible. Upon binding to the host cell receptor CD4, gp120 assumes a conformation that is recognized by the second receptor, CCR5 and/or CXCR4, and by the CD4-induced (CD4i) antibodies. Guided by the X-ray crystal structure of a gp120-CD4-CD4i antibody complex, we introduced changes into gp120 that were designed to stabilize or disrupt this conformation. One mutant, 375 S/W, in which the tryptophan indole group is predicted to occupy the Phe 43 cavity in the gp120 interior, apparently favors a gp120 conformation closer to that of the CD4-bound state. The 375 S/W mutant was recognized as well as or better than wild-type gp120 by CD4 and CD4i antibodies, and the large decrease in entropy observed when wild-type gp120 bound CD4 was reduced for the 375 S/W mutant. The recognition of the 375 S/W mutant by CD4BS antibodies, which are directed against the CD4-binding region of gp120, was markedly reduced compared with that of the wild-type gp120. Compared with the wild-type virus, viruses with the 375 S/W envelope glycoproteins were resistant to neutralization by IgG1b12, a CD4BS antibody, were slightly more sensitive to soluble CD4 neutralization and were neutralized more efficiently by the 2G12 antibody. Another mutant, 423 I/P, in which the gp120 bridging sheet was disrupted, did not bind CD4, CCR5, or CD4i antibodies, even though recognition by CD4BS antibodies was efficient. These results indicate that CD4BS antibodies recognize conformations of gp120 different from that recognized by CD4 and CD4i antibodies.