gebhart/patrepeval huggingface dataset:
The increased density of p38 mitogen-activated protein kinase-immunoreactive microglia in the sensorimotor cortex of aged TgCRND8 mice is associated predominantly with smaller dense-core amyloid plaques (2011)

The role for phosphorylated p38 mitogen-activated protein kinase [p-p38(MAPK)] in β-amyloid plaque deposition [a hallmark of Alzheimer's disease (AD) pathology] remains ambiguous. We combined immunohistochemistry and stereological sampling to quantify the distribution of plaques and p-p38(MAPK)-immunoreactive (IR) cells in the sensorimotor cortex of 3-, 6- and 10-month-old TgCRND8 mice. The aggressive nature of the AD-related human amyloid-β protein precursor expressed in these mice was confirmed by the appearance of both dense-core (thioflavin-S-positive) and diffuse plaques, even in the youngest mice. p-p38(MAPK)-IR cells of the sensorimotor cortex were predominantly co-immunoreactive for the Macrophage-1 (CD11b/CD18) microglial marker. These p-p38(MAPK)-IR microglia were associated with both dense-core and diffuse plaques, but the expected age-dependent increase in the density of plaque-associated p-p38(MAPK)-IR microglia was restricted to dense-core plaques. Furthermore, the density of dense-core plaque-associated p-p38(MAPK)-IR microglia was inversely correlated with the size of the core within the given plaque, which supports a role for these microglia in restricting core growth. p-p38(MAPK)-IR microglia were also observed throughout wildtype and TgCRND8 mouse cortical parenchyma, but the density of these non-plaque-associated microglia remained constant, regardless of age or genotype. We conclude that the constitutive presence of p-p38(MAPK)-IR microglia in aging mouse brain is indicative of a longitudinal role for this kinase in normal brain physiology. We suggest that this fact, as well as the fact that a pool of p-p38(MAPK)-IR microglia appears to restrict β-amyloid plaque core development, needs to be duly considered when ascribing functions for p38(MAPK) signalling in the AD brain.
Neue Cyclosporine aus Tolypocladium inflatum. Die Cyclosporine K–Z (1987)

Novel Cyclosporins from Tolypocladium inflatum . The Cyclosporins K–Z The fungus T. inflatum produces a plethora of oligopeptides, the cyclosporins, which exhibit remarkable biological activities. Cyclosporin A, the main metabolite, represents a potent immunosuppressant which opened new ways in the immunotherapy of bone marrow and organ transplantations. In addition to the already described cyclosporins A–I, we report now the isolation of the cyclosporins K–Z. The structural assignments of these novel congeners are based on chemical degradation, correlation reactions, mass spectra, and extensive analysis of 1 H‐ and 13 C‐NMR spectra. All cyclosporins are cyclic undecapeptides differing from each other by minor variations in the amino‐acid sequence. Comparison of the immunosuppressive and antifungal effects furnished new information concerning structure‐activity relationships.
3-(2-Chlorophenyl)-N-(2-cyano-4-methyl-2-pentyl)-5-methylisoxazole-4-carboxamide (2005)

The title compound, C18H20ClN3O2, is a potent new herbicide. X-ray analysis reveals that the benzene ring is twisted away from the isoxazole ring by 67.7 (1)°. The crystal packing is stabilized by inter­molecular N—H⋯N and C—H⋯O hydrogen bonds.
Immunoselection in vivo: Independent loss of MHC class I and melanocyte differentiation antigen expression in metastatic melanoma (1997)

Peptides derived from melanocyte differentiation antigens have been identified as targets for MHC class I-restricted cytolytic T lymphocytes (CTLs) in human melanoma Regression of antigen-expressing tumors as well as selection of antigen-loss variants in the presence of antigen-specific CTLs have previously been reported. In the present study, we determined the expression of the melanocyte differentiation antigens Melan A/MART-1 and tyrosinase by mRNA analysis and by immunohistochemical staining with the monoclonal antibodies (MAbs) A103 and T311. Co-expression of Melan A/MART-1 and tyrosinase was detected by both methods in 18/20 melanomas tested. However, immunohistochemistry provided additional information on intensity and microheterogeneity of antigen expression that cannot be detected by mRNA analysis as a molecular basis for the escape from CTL recognition of antigen-negative tumor cells. Comparative analysis of repeated biopsies of metastatic lesions in 5 HLA-A2+ patients showed a gradual loss of Melan A/MART-1 expression in 4/5 and of tyrosinase in 2/5 samples in association with tumor progression. However, 3 of these patients had growing antigen-positive tumors in the presence of antigen-specific CTLs. This led us to assess the expression of MHC class I, the essential restriction element for CTL recognition, and of HLA-A2. We found an unexpectedly high frequency of MHC class I-negative tumors (9/20). Loss of MHC class I expression was detected in 3/5 progressive tumors and isolated loss of HLA-A2 in 1/5 tumors. Our results suggest that strategies enhancing the expression of MHC class I and tumor-associated antigens need to be considered in attempts at making vaccination more effective.
Interactions of antibiotics and phagocytes (1983)

Optimal therapy of infections due to organisms capable of surviving within phagocytes would include use of antimicrobials that penetrate phagocytic cells and inactivate intracellular organisms. To establish those characteristics of drug and cell that mediate the antibiotic-phagocyte interaction, we have studied the uptake of radiolabelled antibiotics by rabbit alveolar macrophages (AM), human AM from smokers and non-smokers, and human polymorphonuclear leukocytes (PMN). Relative entries of drug groups into the three types of phagocytic cells were similar. Penicillin G and cephalosporin antibiotics were taken up poorly by phagocytes. Lipid-soluble antibiotics, such as rifampicin and chloramphenicol, were concentrated several-fold (2-5) by phagocytes. Ethambutol, erythromycin and clindamycin were concentrated many-fold (5-50) by phagocytic cells. Human AM of smokers accumulated certain antibiotics more avidly than AM of non-smokers. Clindamycin entry into phagocytes was shown to be an active, energy-requiring process, mediated by the nucleoside transport system. Ingestion of microbial particles by PMN stimulated transport of both clindamycin and nucleoside (adenosine) into the cell.
Functional Protection by Acute Phase Proteins α 1 -Acid Glycoprotein and α 1 -Antitrypsin Against Ischemia/Reperfusion Injury by Preventing Apoptosis and Inflammation (2000)

We propose that the antiapoptotic and anti-inflammatory effects of AGP and AAT contribute to the delayed type of protection associated with ischemic preconditioning and other insults. This mechanism is potentially involved in the course of many clinical conditions associated with I/R injury. Moreover, exogenous administration of these proteins may provide new therapeutic means of treatment.
Use of Recombinant Human Erythropoietin Outside the Setting of Uremia (1997)

survival factor 33 and a mitogen. 34 However, enhancement of
Classroom as Context: Procedural Consequentiality in a Secondary English Classroom (2010)

Discussions abound concerning the role of context when examining data from a conversation analytic (CA) framework. Lively debates concerning the place of gender, class, and other cultural constructs in CA (e.g. Schegloff, 1997; Wetherall, 1998) have led some to conclude that nothing other than the talk itself can be used when practicing CA. However, Schegloff (1991, 1992) has noted at least two instances when the relevance of contextual features can be shown. One of those notions, termed procedural consequentiality (Schegloff, 1992), denotes that a certain aspect of context affects how the interaction unfolds. This brief discussion will analyze such a spate of talk, where the very direction of the conversation is contingent on the fact that a teacher is interacting with students.
BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease (2014)

β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the β-secretase enzyme required for the production of the neurotoxic β-amyloid (Aβ) peptide that is widely considered to have a crucial early role in the etiology of Alzheimer's disease (AD). As a result, BACE1 has emerged as a prime drug target for reducing the levels of Aβ in the AD brain, and the development of BACE1 inhibitors as therapeutic agents is being vigorously pursued. It has proven difficult for the pharmaceutical industry to design BACE1 inhibitor drugs that pass the blood-brain barrier, however this challenge has recently been met and BACE1 inhibitors are now in human clinical trials to test for safety and efficacy in AD patients and individuals with pre-symptomatic AD. Initial results suggest that some of these BACE1 inhibitor drugs are well tolerated, although others have dropped out because of toxicity and it is still too early to know whether any will be effective for the prevention or treatment of AD. Additionally, based on newly identified BACE1 substrates and phenotypes of mice that lack BACE1, concerns have emerged about potential mechanism-based side effects of BACE1 inhibitor drugs with chronic administration. It is hoped that a therapeutic window can be achieved that balances safety and efficacy. This review summarizes the current state of progress in the development of BACE1 inhibitor drugs and the evaluation of their therapeutic potential for AD.
Highly Effective Water-Soluble Fluorescence Quenchers of Conjugated Polymer Thin Films in Aqueous Environments (2006)

ADVERTISEMENT RETURN TO ISSUECommunication to the...Communication to the EditorNEXTHighly Effective Water-Soluble Fluorescence Quenchers of Conjugated Polymer Thin Films in Aqueous EnvironmentsGuy D. Joly, Lars Geiger, Steven E. Kooi, and Timothy M. SwagerView Author Information Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139 Cite this: Macromolecules 2006, 39, 21, 7175–7177Publication Date (Web):September 14, 2006Publication History Received18 July 2006Revised15 August 2006Published online14 September 2006Published inissue 1 October 2006https://pubs.acs.org/doi/10.1021/ma061618hhttps://doi.org/10.1021/ma061618hrapid-communicationACS PublicationsCopyright © 2006 American Chemical SocietyRequest reuse permissionsArticle Views973Altmetric-Citations29LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Hydrophobicity,Monolayers,Pyridines,Solution chemistry,Thin films Get e-Alerts
PDC Bit Selection through Cost Prediction Estimates Using Crossplots and Sonic Log Data (1993)

Abstract PDC bit technology has developed into an attractive and economical alternative in many drilling scenarios. Although much has been done for bit selection and optimization for tricone bits, much is still to be done for PDC bits, due to the difficulty of modeling the PDC wear, bit whirl and account for the many types and geometrical configurations of the existing PDC in the market today. This paper presents a method to select a PDC bit through predicting the lowest drilling cost for a given situation of interest, given the shear stress level it will be subjected to. The method uses all data from the PDC bit records, therefore containing many different lithologies and rock properties. It is based on the comparison of past bit performance and correlates it to the formation's shear stress. Graphic outputs play a key role in the analysis to queue in to a particular data group of interest within an extensive bit database. The proposed procedures have been validated using data from 49 wells from 6 Brazilian fields and the results showed that the cost savings are significant. Examples are presented and discussed.
Epidemiologic Study of Vibrio cholerae O1 and O139 in Thailand: At the Advancing Edge of the Eighth Pandemic (1996)

Vibrio cholerae O139 Bengal emerged on the Indian subcontinent in late 1992 and was first recognized in Thailand in 1993. To characterize the epidemiology of this disease, a hospital-based case-control study was conducted in Samutsakorn, a port city 30 km southwest of Bangkok. Between November 15, 1993, and June 3, 1994, 366 patients were confirmed to have cholera by culture, including 165 (45%) with O139 Bengal, 191 (52%) with O1 Ogawa, and 10 (3%) with both serogroups. During the same time period the previous year, 319 culture-confirmed cholera cases occurred, all serogroup O1. Questionnaires were obtained from 105 patients with O139 Bengal and 103 with O1 infections; for each case patient, two asymptomatic age- and sex-matched control persons were selected. Of the patients with O139 Bengal infections, 93% were adults (> or = 15 years) compared with 92% of patients with O1 infections. Risk factors for cholera identified by case-control comparisons were similar for the two serogroups and included consumption of untreated water, uncooked seafood, and food served at group gatherings. V. cholerae O139 Bengal has emerged in Thailand as a cause of endemic cholera, with epidemiologic features and incidence similar to those of the preexisting O1 strain.
Effects of Rinses with an Acidic Calcium Phosphate Solution on Fluoride Uptake, Caries, and in situ Plaque pH in Rats (1988)

The effects of oral rinses on enamel fluoride uptake, caries, and plaque pH in rats were investigated by use of (1) an acidic calcium phosphate solution (CPS) saturated with dicalcium phosphate dihydrate (DCPD) and (2) a 1% fluoride solution. Osborne-Mendel rats, 19 days of age, were randomly assigned to one of four mouth-rinse treatment groups, with the two consecutively administered rinses being: H2O-H2O; H2O-F; CPS-H2O; and CPS-F. The treatments were administered on days 1 through 4, and the animals were provided with a cariogenic challenge throughout the study. The groups treated with F exhibited significantly higher mean levels of enamel-bound F than did the non-F groups. Furthermore, CPS significantly increased uptake of F by enamel when used as an adjunct to the F treatment. The caries scores of the CPS-F and H2O-F groups were not statistically different; however, a strong negative correlation was observed between enamel F content and caries scores, indicating that as more F was incorporated into the teeth, less caries formation occurred. Despite the significant differences in enamel F and caries scores among some of the treatment groups, post mortem in situ plaque pH drop in response to a sucrose rinse showed no differences among these groups.
RNA-binding protein conserved in both microtubule- and microfilament-based RNA localization (1998)

Vg1 mRNA translocation to the vegetal cortex of Xenopus oocytes requires intact microtubules, and a 3' UTR cis-acting element (termed VLE), which also mediates sequence-specific binding of several proteins. One protein, the 69-kD Vg1 RBP, associates Vg1 RNA to microtubules in vitro. Here we show that Vg1 RBP-binding sites correlate with vegetal localization. Purification and cloning of Vg1 RBP revealed five RNA-binding motifs: four KH and one RRM domains. Surprisingly, Vg1 RBP is highly homologous to the zipcode binding protein implicated in the microfilament-mediated localization of beta actin mRNA in fibroblasts. These data support Vg1 RBP's direct role in vegetal localization and suggest the existence of a general, evolutionarily conserved mechanism for mRNA targeting.
The structure and regulation of expression of the murine fast skeletal troponin C gene. Identification of a developmentally regulated, muscle-specific transcriptional enhancer. (1990)

Fast skeletal muscle troponin C (sTnC) is the calcium-binding subunit of the myofibrillar thin filament that regulates excitation-contraction coupling. Utilizing a polymerase chain reaction cloning strategy, we have isolated cDNA clones encoding murine sTnC. The 160-amino acid sTnC protein shares 70% amino acid sequence identity with the slow/cardiac isoform of troponin C (cTnC). However, three areas of significant sequence divergence were identified. Southern blot analyses demonstrated that murine sTnC is encoded by a single copy gene that is distinct from that which encodes cTnC. Northern blot analyses showed that the sTnC gene is expressed exclusively in skeletal muscle (extensor digitorum and anterior tibialis) and not in neonatal or adult heart, brain, kidney, liver, lung, or testes. Studies of the murine C2C12 myoblast cell line demonstrated that sTnC gene expression is developmentally regulated during the differentiation of these myoblasts into myotubes. A full-length murine sTnC genomic clone was isolated and characterized by DNA sequence, primer extension, and S1 nuclease protection analyses. The sTnC gene is composed of six exons spanning 2.6 kilobase pairs of genomic DNA. Although the introns do not divide the gene into functional domains, the intron-exon borders are nearly identical to those of the other members of the troponin C multigene family. Transient transfection assays using chloramphenicol acetyltransferase reporter plasmids demonstrated that the sTnC promoter alone is relatively inactive in muscle cells and that high level sTnC gene expression in these cells is controlled by a potent transcriptional enhancer element located within the first intron of the gene. In additional transfection experiments, the sTnC enhancer was shown to display three important biological activities. (i) It was required for high level transcription from the sTnC promoter in muscle cells; (ii) its activity was muscle cell specific; and (iii) its activity was developmentally regulated during the differentiation of C2C12 myoblasts to myotubes. Taken together, these data define the sTnC gene as an excellent model system for studies of developmentally regulated gene expression in skeletal muscle.
Lung volume-related changes in the pharyngeal area of obese females with and without obstructive sleep apnoea (1989)

The majority of male patients with obstructive sleep apnoea (OSA) have an abnormal pharyngeal structure and function, with episodic complete airway occlusion during sleep. Since OSA is less common in females than in males, it is possible that other abnormalities are active in female patients with OSA. Consequently, we measured pharyngeal area and its lung volume-related changes (LVRC) from functional residual capacity (FRC) to residual volume (RV) in overweight females, 14 with OSA and 14 without OSA. Pharyngeal areas were measured using the acoustic reflection technique. While there were no significant differences in pharyngeal area between the OSA and control groups at either FRC (mean +/- SD, 3.49 +/- 0.46 cm2 vs 3.08 +/- 0.63 cm2) or RV (2.86 +/- 0.47 cm2 vs 2.67 +/- 0.49 cm2), the reduction in pharyngeal area between FRC and RV was significantly greater in the OSA group (0.63 +/- 0.23 cm2 vs 0.33 +/- 0.32 cm2, p less than 0.05). Furthermore, although the expiratory reserve volume (ERV) was not significantly different between the two groups (0.4 +/- 0.2 l vs 0.4 +/- 0.3 l), LVRC, defined as the reduction in pharyngeal area normalized by ERV, was significantly higher in the females with OSA than in the non-apnoeic controls (2.68 +/- 2.24 cm2.l-1 vs 1.17 +/- 1.23 cm2.l-1, p less than 0.02). We conclude that females with OSA have abnormal pharyngeal mechanics similar to males with OSA.
Synthesis and Self-Assembly of Functionalized Hexa-peri-hexabenzocoronenes (2000)

Monolayers of hexa-alkyl substituted derivatives of hexa-peri-hexabenzocoronene (HBC) 1b have previously been investigated by scanning tunneling microscopy (STM) and scanning tunneling spectroscopy (STS). It is expected that different functional groups (electron donating or withdrawing) connected to the aromatic core will influence the packing pattern and possibly the current-voltage characteristics as well. In order to provide suitable model systems, a new synthetic approach to synthesize functionalized HBC derivatives has been developed. This was accomplished by [4 + 2]-cycloaddition of suitably bromo-substituted diphenylacetylenes and 2,3,4,5-tetraarylcyclopenta-2,4-dien-1-ones followed by an oxidative cyclodehydrogenation with iron(III) chloride/nitromethane. Using this strategy three different substitution patterns were synthesized: 2-bromo-5,8,11.14,17-pentadodecylhexa-pecri-hexabenzocoronene (2a), 2,5-dibromo-8,11,14,17-pentadodecylhexa-peri-hexabenzocoronene (2b), and 2,11-dibromo5,8,14,17-pentadodecylhexa-peri-hexa-benzocoronene (2c). These bromo-substituted HBC derivatives were subjected to palladium catalyzed coupling reactions to give donor (alkoxy, amino) as well as acceptor (ester, cyano) substituted derivatives. The self-assembly of these new HBC derivatives was studied in the bulk as well as at an interface. DSC, optical microscopy, and X-ray diffraction revealed the existence of columnar mesophases. The bulk structure in the mesophase is largely insensitive to changes of the substitution pattern; however, in situ scanning tunneling microscopy at the solid-fluid interface between an organic solution of the HBC derivative and highly oriented pyrolytic graphite reveals different packing patterns of the first adsorbed monolayer.
Induction of Keratinocyte Proliferation and Lymphocytic Infiltration by In Vivo Introduction of the IL-6 Gene into Keratinocytes and Possibility of Keratinocyte Gene Therapy for Inflammatory Skin Diseases Using IL-6 Mutant Genes (1998)

To understand biological function of IL-6 in the skin in vivo, we constructed a vector that strongly expressed human IL-6 in keratinocytes and introduced it into rat keratinocytes in vivo by the naked DNA method. The overexpression of IL-6 induced macroscopic erythema and histologically evident keratinocyte proliferation and lymphocytic infiltration in the treated area of rat skin. Since previous studies using IL-6 transgenic mice have not shown skin inflammation of these mice, our result provides the first evidence that IL-6 is related to the pathogenesis of inflammatory skin diseases. ELISA suggested that a certain degree of transgenic IL-6 expression in keratinocytes was required for inducing skin inflammation. Cytokine profile in rat keratinocytes after the gene introduction was examined by reverse transcriptase-PCR assay and revealed that gene expression of rat IL-1alpha and TNF-alpha showed no marked change until 24 h, whereas that of rat IL-6 and TGF-alpha increased with time. We then introduced and expressed the IL-6 mutant genes, which were designed to behave as IL-6Ralpha antagonists, and found that their ability to induce erythema was lower than that of the wild-type gene. Furthermore, preintroduction of some mutant genes delayed the erythema induced by postintroduction of the wild-type IL-6 gene, suggesting that the mutant forms of IL-6 prevent wild-type IL-6 from binding to IL-6Ralpha. This result indicates that keratinocyte gene therapy may be possible for inflammatory skin diseases using IL-6 mutant genes.