gebhart/patrepeval huggingface dataset:
CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis (2015)

Dendritic cells (DCs) are critical for immune homeostasis. To target DCs, we generated a mouse line with Flip deficiency in cells that express cre under the CD11c promoter (CD11c-Flip-KO). CD11c-Flip-KO mice spontaneously develop erosive, inflammatory arthritis, resembling rheumatoid arthritis, which is dramatically reduced when these mice are crossed with Rag(-/-) mice. The CD8α(+) DC subset is significantly reduced, along with alterations in NK cells and macrophages. Autoreactive CD4(+) T cells and autoantibodies specific for joint tissue are present, and arthritis severity correlates with the number of autoreactive CD4(+) T cells and plasmablasts in the joint-draining lymph nodes. Reduced T regulatory cells (Tregs) inversely correlate with arthritis severity, and the transfer of Tregs ameliorates arthritis. This KO line identifies a model that will permit in depth interrogation of the pathogenesis of rheumatoid arthritis, including the role of CD8α(+) DCs and other cells of the immune system.
Ultra-high-capacity DWDM transmission system by multilevel modulations and digital coherent detection (2009)

In this paper, we will report our latest experimental results. These includes 20 times 112-Gb/s PDM-RZ-QPSK transmission over 1540-km of standard single mode fiber (SSMF), a record capacity of 17 Tb/s within the C-band optical bandwidth (4.025 THz) over 660 km of ultra-low-loss fiber using 161 times 114-Gbps PDM-RZ-8PSK formats, and hybrid 10 times 112 Gb/s PDM-RZ-QPSK and 10 times 44 Gb/s PDM-NRZ-QPSK transmission with 25-GHz channel spacing over 1600 km of SSMF.
ChemInform Abstract: Novel 4‐(Trimethylsilyl)aminoalkanes and 4‐(Trimethylsilyl)aminoalk‐2‐enes, via a 1,5‐Hydride Shift, in the Reaction of α‐Unsaturated Silanes with Aminomethylbenzotriazoles. (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Antioxidant and Antimicrobial Activity of Cissus quadrangularis L. (2003)

Extracts of Cissus quadrangularis L. were tested for antioxidant activity by beta-carotene linoleic acid model and also by 1,1-diphenyl-2-picrylhydrazyl model. The ethyl acetate fraction of both fresh and dry stem extracts at a concentration of 100 ppm showed 64.8% antioxidant activity in the beta-carotene linoleic acid system and 61.6% in the 1,1-diphenyl-2-picrylhydrazyl system. This fraction showed the presence of sterols, vitamin C, and tannins as phytoconstituents. The antioxidant activity of methanol extract and aqueous extract were comparatively less significant than that of ethyl acetate extract, and n-hexane extract showed the least activity. The ethyl acetate extract and methanol extract of both fresh and dry stems further exhibited antimicrobial activity against Gram-positive bacteria, including Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, and Streptococcus species. The results of the study have implications in the use of C. quadrangularis as an antibacterial agent and more so as an antioxidant in several applications requiring these properties.
Expression of macrophage-lymphocyte Fc receptors in Madin-Darby canine kidney cells: polarity and transcytosis differ for isoforms with or without coated pit localization domains. (1989)

Many cells of the immune system and certain epithelia express receptors for the Fc domain of IgG (FcR). On mouse macrophages and lymphocytes, two distinct receptor isoforms have been identified, designated FcRII-B1 and FcRII-B2. The isoforms are identical except for an in-frame insertion of 47 amino acids in the cytoplasmic tail of FcRII-B1 that blocks its ability to be internalized by clathrin-coated pits. We have recently found that at least one IgG-transporting epithelium, namely placental syncytial trophoblasts, expresses transcripts encoding a receptor similar or identical to macrophage-lymphocyte FcRII. To determine whether FcRII of hematopoietic cells might also function as a transcytotic receptor if expressed in epithelial cells, FcRII-B1 and -B2 were transfected into Madin-Darby canine kidney (MDCK) cells and grown on permeable filter units. The two FcRII isoforms exhibited different patterns of polarized expression: FcRII-B1 was localized mainly to the apical plasma membrane domain, whereas FcRII-B2 was found predominantly on the basolateral surface. As expected for FcR in placenta, FcRII-B2 and to a lesser extent FcRII-B1 mediated transcellular transport of IgG-complexes from the apical to the basolateral plasma membrane. Neither receptor mediated transcytosis in the opposite direction, although FcRII-B2 also delivered ligand to lysosomes when internalized from either the basolateral or apical domains. Furthermore, FcRII-B2 was capable of transporting monovalent antireceptor antibody Fab fragments across the cell, suggesting that transcytosis was not dependent on receptor cross-linking. These findings suggest the possibility that FcRII can mediate transepithelial IgG transport when expressed in placental syncytial trophoblasts in addition to its "classical" endocytic and signaling activities when expressed in macrophages. Because FcRII-B1 and -B2 are expressed with distinct polarities, the results also suggest that interactions with clathrin-coated pits may play a role in generating the polarized distribution of at least some plasma membrane proteins in MDCK cells.
Isolation and characterization of full-length functional cDNA clones for human carcinoembryonic antigen. (1987)

Carcinoembryonic antigen (CEA) expression is perhaps the most prevalent of phenotypic changes observed in human cancer cells. The molecular genetic basis of this phenomenon, however, is completely unknown. Twenty-seven CEA cDNA clones were isolated from a human colon adenocarcinoma cell line. Most of these clones are full length and consist of a number (usually three) of surprisingly similar long (534 base pairs) repeats between a 5' end of 520 base pairs and a 3' end with three different termination points. The predicted translation product of these clones consists of a processed signal sequence of 34 amino acids, an amino-terminal sequence of 107 amino acids, which includes the known terminal amino acid sequence of CEA, three repeated domains of 178 amino acids each, and a membrane-anchoring domain of 27 amino acids, giving a total of 702 amino acids and a molecular weight of 72,813 for the mature protein. The repeated domains have conserved features, including the first 67 amino acids at their N termini and the presence of four cysteine residues. Comparisons with the amino acid sequences of other proteins reveals homology of the repeats with various members of the immunoglobulin supergene family, particularly the human T-cell receptor gamma chain. CEA cDNA clones in the SP-65 vector were shown to produce transcripts in vitro which could be translated in vitro to yield a protein of molecular weight 73,000 which in turn could be precipitated with CEA-specific antibodies. CEA cDNA clones were also inserted into an animal cell expression vector and introduced by transfection into mammalian cell lines. These transfectants produced a CEA-immunoprecipitable glycoprotein which could be visualized by immunofluorescence on the cell surface.
Synthese von 2‐Amino‐4‐alkylmercapto‐6‐aryl‐1, 3, 5‐triazinen und 4‐Amino‐6‐alkylmercapto‐2‐aryl‐5‐pyrimidincarbonitril (1972)

Abstract Die Darstellung und die Eigenschaften von 2‐Amino‐4‐alkylmercapto‐6‐aryl‐1, 3, 5‐triazinen und 4‐Amino‐6‐alkylmercapto‐2‐aryl‐5‐pyrimidincarbonitril werden beschrieben.
The Avon Longitudinal Study of Parents and Children (ALSPAC): a resource for genetic epidemiology (2004)

The Avon Longitudinal Study of Parents and Children (ALSPAC) has collected detailed phenotypic and environmental information from pregnancy onwards on approximately 14 000 babies born in 1991-1992. A DNA bank on over 10 000 mothers and children has been established with generic consent for (undisclosed) genetic analysis, and cell lines on both children and parents are planned. As a multigenerational population cohort unselected by disease, trait or exposure, ALSPAC is uniquely placed to explore the genetic and environmental determinants of adverse developmental responses and common disease. Added value for genetic epidemiology generally is the ability to detect distortion of the expected Mendelian 50:50 transmission of alleles to study subjects (e.g. due to differential loss of embryos of one genotype) or to test for heterosis, i.e. whether heterozygotes have a greater or lesser effect than either homozygote. Finally, phenome scans (a fixed format analysis of the associations between a genotype of interest and thousands of outcome variables from the cohort database) could be used as a screening tool to test whether certain classes of genetic variation have more impact than others on human health and development.
Inflammatory macrophage migration requires MMP-9 activation by plasminogen in mice (2008)

Inflammation plays a critical role in the development of cardiovascular diseases. Infiltration of leukocytes to sites of injury requires their exit from the blood and migration across basement membrane; this process has been postulated to require remodeling of the ECM. Plasminogen (Plg) is a protease that binds to the ECM and, upon conversion to plasmin, degrades multiple ECM proteins. In addition, plasmin directly activates MMPs. Here, we used Plg(-/-) mice to investigate the role of Plg in inflammatory leukocyte migration. After induction of peritonitis by thioglycollate injection, we found that Plg(-/-) mice displayed diminished macrophage trans-ECM migration and decreased MMP-9 activation. Furthermore, injection of the active form of MMP-9 in Plg(-/-) mice rescued macrophage migration in this model. We used periaortic application of CaCl2 to induce abdominal aortic aneurysm (AAA) and found that Plg(-/-) mice displayed reduced macrophage infiltration and were protected from aneurysm formation. Administration of active MMP-9 to Plg(-/-) mice promoted macrophage infiltration and the development of AAA. These data suggest that Plg regulates macrophage migration in inflammation via activation of MMP-9, which, in turn, regulates the ability of the cells to migrate across ECM. Thus, targeting the Plg/MMP-9 pathway may be an attractive approach to regulate inflammatory responses and AAA development.
Placebo-Controlled Comparison of Three Dose-Regimens of 5-Hydroxytryptophan Challenge Test in Healthy Volunteers (2002)

Single-dose administration of 5-hydroxytryptophan (5-HTP) is regularly used as a challenge test of the serotonergic system. The use of 5-HTP has been limited by an apparent small window between the occurrence of neuroendocrine endpoints and the occurrence of side effects. Therefore, many dosing strategies have been tried with and without concurrent administration of carbidopa, a peripheral inhibitor of the decarboxylation from 5-HTP to serotonin. The aim of the current study was to assess the relation between pharmacokinetics and pharmacodynamics of 5-HTP. Twelve healthy male volunteers were included in a placebo-controlled, randomized, four-way crossover, double-blind, single-dose investigation of oral 5-HTP with or without coadministration of carbidopa. The four dose regimens were placebo, 5-HTP 100 mg, 5-HTP 200 mg, and 5-HTP 100 mg with coadministration of carbidopa 100 mg and 50 mg at 3 hours before and 3 hours after the administration of 5-HTP, respectively. The last regimen resulted in a doubling of the elimination half-life, an apparent clearance at least 14 times smaller, and a 15.4 times greater area under the curve compared with 5-HTP 100 mg without carbidopa. Furthermore, it was the only regimen to induce a significant change in cortisol and prolactin. It did not induce any change in subjective psychologic symptoms or cardiovascular parameters, but it was the only regimen to induce some nausea in three participants. The authors conclude that this regimen of 5-HTP 100 mg plus carbidopa is a relatively simple, effective, and tolerable challenge of the presynaptic serotonergic system. Further increase of the dose of 5-HTP might improve the size of the effect on endpoints as long as the tolerability remains good.
Transcriptional analyses and mapping of the ospC gene in Lyme disease spirochetes (1993)

In Lyme disease spirochetes, the ospC gene encodes a 22.7-kDa protein referred to as either the pC or the OspC protein. Using a variety of electrophoretic approaches followed by Southern blotting and probing with oligonucleotide probes, we mapped the ospC gene to a circular 26-kb plasmid. The ospC gene represents the first gene to be mapped to a circular plasmid in Lyme disease spirochetes. The occurrence of this gene in isolates belonging to each of the three Lyme disease-associated species, Borrelia burgdorferi, Borrelia garinii, and the VS461 group, was evaluated. The ospC gene was found to occur in all 21 isolates tested from each of the three species. Differential hybridization with a series of ospC probes in both Northern (RNA) and Southern blot analyses demonstrated that there is sequence variability in the ospC gene among isolates. While the gene was found to be present in all isolates, not all actively transcribed the gene. Transcriptional start site analyses suggest that the gene may be under the control of multiple promoters that are highly similar in nucleotide sequence.
Cation Transport in Escherichia coli (1967)

When Escherichia coli K-12 is grown in media containing limiting amounts of K, growth continues normally until all the extracellular K has been consumed. Thereafter the rates of growth, glucose consumption, and oxygen consumption decrease progressively, and the cell contents of K and P fall. These changes, referred to as K limitation, are all reversed by the addition of K. By specifically altering the ionic composition of the cells it was shown that these metabolic disturbances are not due to changes in the cell content of K or Na, but are directly related to the absence of K from the extracellular medium. The cell pool of inorganic P and the uptake of PO(4) from the medium are low in K-limited cells and are immediately stimulated by the addition of K, suggesting that the primary effect of K limitation is to inhibit PO(4) uptake. All the metabolic effects of K limitation can be attributed to inhibition of PO(4) uptake. The requirement of extracellular K for PO(4) uptake may be due to a coupling between the uptake of K and PO(4).
Starburst dendrimers. III. The importance of branch junction symmetry in the development of topological shell molecules (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStarburst dendrimers. III. The importance of branch junction symmetry in the development of topological shell moleculesDonald A. Tomalia, M. Hall, and David M. HedstrandCite this: J. Am. Chem. Soc. 1987, 109, 5, 1601–1603Publication Date (Print):March 1, 1987Publication History Published online1 May 2002Published inissue 1 March 1987https://pubs.acs.org/doi/10.1021/ja00239a068https://doi.org/10.1021/ja00239a068research-articleACS PublicationsRequest reuse permissionsArticle Views476Altmetric-Citations145LEARN 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
High-throughput methylation profiling by MCA coupled to CpG island microarray (2007)

An abnormal pattern of DNA methylation occurs at specific genes in almost all neoplasms. The lack of high-throughput methods with high specificity and sensitivity to detect changes in DNA methylation has limited its application for clinical profiling. Here we overcome this limitation and present an improved method to identify methylated genes genome-wide by hybridizing a CpG island microarray with amplicons obtained by the methylated CpG island amplification technique (MCAM). We validated this method in three cancer cell lines and 15 primary colorectal tumors, resulting in the discovery of hundreds of new methylated genes in cancer. The sensitivity and specificity of the method to detect hypermethylated loci were 88% and 96%, respectively, according to validation by bisulfite-PCR. Unsupervised hierarchical clustering segregated the tumors into the expected subgroups based on CpG island methylator phenotype classification. In summary, MCAM is a suitable technique to discover methylated genes and to profile methylation changes in clinical samples in a high-throughput fashion.
Epizootic of equine protozoal myeloencephalitis on a farm (1997)

EPM may develop as an epizootic. In the horses of this report subtle clinical signs that were originally considered unimportant ultimately progressed to obvious neurologic signs. Adverse effects associated with EPM treatment included worsening of neurologic signs, anemia, abortion, and leukopenic and febrile episodes.
Clinical significance of drug resistance in HIV-1 infection (1996)

Laboratory evidence for drug resistance does not necessarily imply clinical drug failure. Emergence of (-)-2',3-d-deoxy-3'-thiacytidine (3TC, lamivudine) resistance may potentiate activity of zidovudine in patients treated with 3TC/zidovudine combination therapy. Novel therapeutic strategies that exploit this mutational interaction, or challenge the limits of adaptation of the virus, may lead to more effective long-term suppression of HIV-1.
Variable Absorption of Carbidopa Affects Both Peripheral and Central Levodopa Metabolism (2000)

Carbidopa (CD), a competitive inhibitor of aromatic l-amino acid decarboxylase that does not cross the blood-brain barrier, is routinely administered with levodopa (LD) to patients with Parkinson disease (PD) to reduce the peripheral decarboxylation of LD to dopamine. Using a stable isotope-labeled form of LD, the authors examined in 9 PD patients the effects of variable CD absorption on peripheral and central LD metabolism. Subjects were administered orally 50 mg of CD followed in 1 hour by a slow bolus intravenous infusion of 150 mg stable isotope-labeled LD (ring 1',2',3',4',5',6'-13C). Eight patients underwent a lumbar puncture 6 hours following the infusion. Blood and cerebrospinal fluid (CSF) samples were analyzed for labeled and unlabeled metabolites using a combination of high-performance liquid chromatography and mass spectrometry. When patients were divided into "slow" and "rapid" CD absorption groups, significantly greater peripheral LD decarboxylation (as measured by area under the curve [AUC]-labeled serum HVA) was noted in the poor absorbers (p = 0.05, Mann-Whitney U test). Elimination half-lives for serum LD did not differ between groups, suggesting a further capacity for decarboxylation inhibition in the "rapid" absorbers. A significant correlation between AUC serum CD and percent-labeled HVA in CSF was found for all patients (R = 0.786, p = 0.02). "Rapid" as compared to "slow" CD absorbers had significantly more percent-labeled CSF HVA (60 vs. 49, p = 0.02, Mann-Whitney U test), indicating greater central-labeled DA production in the better CD absorbers. The data suggest that peripheral aromatic l-amino acid decarboxylase activity is not saturated at CD doses used in current practice. The authors believe that future studies to better examine a dose dependence of CD on peripheral LD decarboxylation and LD brain uptake are warranted.
Duloxetine: a new pharmacologic therapy for stress urinary incontinence. (2004)

The dual serotonin (5-HT)/norepinephrine (NE) reuptake inhibitor duloxetine shows promise as a pharmacologic therapy for stress urinary incontinence. This agent modulates lower urinary tract function through selective inhibition of 5-HT and NE receptor sites. It works centrally at Onuf’s nucleus to increase activity of the pudendal nerve. Duloxetine facilitates sphincter activity during urine storage but not during voiding, maintaining the bladder-sphincter synergy. Because it inhibits both 5-HT and NE reuptake, duloxetine appears to offer an advantage over agents that inhibit reuptake of a single neurotransmitter.
Incorporation of an Isoleucine Zipper Motif Enhances the Biological Activity of Soluble CD40L (CD154) (1999)

Recent progress in the understanding of immune function indicates that the interaction of CD40L with its receptor, CD40, plays a pivotal role in both humoral immunity and cell-mediated defense against pathogens. Functional studies of this interaction on both dendritic cells and malignant cells have demonstrated that CD40L also plays an important role in immune surveillance and anti-tumor immunity. CD40L exists in nature predominantly as a membrane-anchored molecule. To develop CD40L as a potential therapeutic, it is important to optimize soluble forms of this molecule that could be used in a clinical setting. Several reports have shown that soluble forms of CD40L, like CD40 antibodies, are biologically active. In the present report we demonstrate that the incorporation of an isoleucine zipper trimerization motif significantly enhances the biological activity of soluble CD40L.
Oncogenes and cancer. Proceedings of the 17th International Symposium of the Princess Takamatsu Cancer Research Fund. Tokyo, 1986. (1986)

Discoveries that a small subset of cellular genes --- proto-oncogenes --- are frequent targets of carinogenic insults or chance that convert them to oncogenes have opened new areas of approach to understanding and eventually controlling the events leading to cancer. New technology has made it possible not only to identify genes involved in the etiology of cancer, but to dissect their molecular composition. This symposium brought together scientists from areas of carcinogenesis and molecular biology to review the state-of-the-art in this field. The papers presented in this proceedings volume can be grouped into four broad areas: the mechanisms of onc gene activation and associations of onc genes with tumours, the mechanisms of onc gene action, the physiology of proto-onc genes, and the discovery and characterization of new onc genes.