gebhart/patrepeval huggingface dataset:
Flow Cytometric Microsphere-Based Immunoassay: Analysis of Secreted Cytokines in Whole-Blood Samples from Asthmatics (2001)

The ability of flow cytometry to resolve multiple parameters was used in a microsphere-based flow cytometric assay for the simultaneous determination of several cytokines in a sample. The flow cytometer microsphere-based assay (FMBA) for cytokines consists of reagents and dedicated software, specifically designed for the quantitative determination of cytokines. We have made several improvements in the multiplex assay: (i) dedicated software specific for the quantitative multiplex assay that processes data automatically, (ii) a stored master calibration curve with a two-point recalibration to adjust the stored curve periodically, and (iii) an internal standard to normalize the detection step in each sample. Overall analytical performance, including sensitivity, reproducibility, and dynamic range, was investigated for interleukin-4 (IL-4), IL-6, IL-10, IL-12, gamma interferon (IFN-gamma), and tumor necrosis factor alpha. These assays were found to be reproducible and accurate, with a sensitivity in the picograms-per-milliliter range. Results obtained with FMBA correlate well with commercial enzyme-linked immunosorbent assay data (r > 0.98) for all cytokines assayed. This multiplex assay was applied to the determination of cytokine profiles in whole blood from atopic and nonatopic patients. Our results show that atopic subjects' blood produces more IL-4 (P = 0.003) and less IFN-gamma (P = 0.04) than the blood of nonatopic subjects. However, atopic asthmatic subjects' blood produces significantly more IFN-gamma than that of atopic nonasthmatic subjects (P = 0.03). The results obtained indicate that the FMBA technology constitutes a powerful system for the quantitative, simultaneous determination of secreted cytokines in immune diseases.
Expression of the zinc finger transcription factor zDC (Zbtb46, Btbd4) defines the classical dendritic cell lineage (2012)

Classical dendritic cells (cDCs), monocytes, and plasmacytoid DCs (pDCs) arise from a common bone marrow precursor (macrophage and DC progenitors [MDPs]) and express many of the same surface markers, including CD11c. We describe a previously uncharacterized zinc finger transcription factor, zDC (Zbtb46, Btbd4), which is specifically expressed by cDCs and committed cDC precursors but not by monocytes, pDCs, or other immune cell populations. We inserted diphtheria toxin (DT) receptor (DTR) cDNA into the 3' UTR of the zDC locus to serve as an indicator of zDC expression and as a means to specifically deplete cDCs. Mice bearing this knockin express DTR in cDCs but not other immune cell populations, and DT injection into zDC-DTR bone marrow chimeras results in cDC depletion. In contrast to previously characterized CD11c-DTR mice, non-cDCs, including pDCs, monocytes, macrophages, and NK cells, were spared after DT injection in zDC-DTR mice. We compared immune responses to Toxoplasma gondii and MO4 melanoma in DT-treated zDC- and CD11c-DTR mice and found that immunity was only partially impaired in zDC-DTR mice. Our results indicate that CD11c-expressing non-cDCs make significant contributions to initiating immunity to parasites and tumors.
Human plasma lecithin-cholesterol acyltransferase. The vicinal nature of cysteine 31 and cysteine 184 in the catalytic site. (1988)

Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme which catalyzes the transacylation of the fatty acid at the sn-2 position of lecithin to cholesterol forming lysolecithin and cholesteryl ester. The substrates for and products of this reaction are present within the plasma lipoproteins upon which the enzyme acts to form the majority of cholesteryl ester in human plasma. We proposed a covalent catalytic mechanism of action for LCAT (Jauhiainen, M., and Dolphin, P. J. (1986) J. Biol. Chem. 261, 7032-7034) in which serine and histidine residues mediate lecithin cleavage and two cysteine residues cholesterol esterification. With the aid of sulfhydryl reactive trivalent organoarsenical compounds which are specific for vicinal thiols we have probed the geometry of the catalytic site. p-Aminophenylarsendichloride noncompetitively inactivates cholesterol esterification (Ki = 0.23 mM) by LCAT via alkylation of both catalytic cysteine residues. This reagent does not significantly inactivate lecithin cleavage by LCAT. Full enzyme activity is restored by treatment with 2,3-dimercapto-1-propanesulfonic acid. Treatment of LCAT with p-bromoacetylaminophenylarsenoxide blocks the subsequent incorporation of diisopropyl fluorophosphate and iodoacetamide and inactivates both cholesterol esterification and lecithin cleavage. These activities are not restored following 2,3-dimercapto-1-propanesulfonic acid treatment. However, the reduced cysteine thiols are regenerated and can catalyze cholesteryl arachidonate formation from arachidonyl-CoA. The control reagent, bromoacetylaniline, which lacks the sulfhydryl-reactive arsenical moiety, does not inactivate LCAT nor is this reagent incorporated into the LCAT protein. We conclude that the two catalytic cysteine residues of LCAT (Cys31 and Cys184) are vicinal with a calculated distance between their sulfur atoms of 3.50-3.62 A. The additional residue alkylated by the bifunctional reagent is within the catalytic site and may represent a previously identified catalytic serine or histidine residue.
CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. (1996)

Dendritic cells are potent antigen-presenting cells that initiate primary immune responses. Although dendritic cells derive from bone marrow stem cells, the intermediate stages in their development remain unknown. In this study, plastic-adherent blood monocytes (CD14+, CD1a-) cultured for 7 days with granulocyte-monocyte colony-stimulating factor, interleukin 4, and tumor necrosis factor alpha were shown to differentiate into CD1a+ CD83+ dendritic cells. These cells displayed all phenotypic and morphologic characteristics of mature dendritic cells and were the most potent stimulatory cells in allogeneic mixed leukocyte reactions. The identification of specific culture conditions that generate large numbers of dendritic cells from purified monocytes uncovers an important step in dendritic cell maturation that will allow the further characterization of their role in autoimmune diseases, graft rejection, and human immunodeficiency virus infection.
Accumulation of P-Selectin in the Lumen of Irradiated Blood Vessels (1999)

Ionizing radiation induces the inflammatory response in part through leukocyte binding to cell adhesion molecules that are expressed on the vascular endothelium. We studied the effects of X radiation on the pattern of immunohistochemical staining of CD62P (P-selectin). P-selectin was localized within cytoplasmic granules in the untreated vascular endothelium. Immunohistochemical staining of P-selectin was observed at the luminal surface of vascular endothelium within 1 h of irradiation. Increased P-selectin staining at the blood-tissue interface occurred primarily in pulmonary and intestinal blood vessels. To determine whether localization of P-selectin at the vascular lumen occurs through exocytosis of endothelial cell stores in addition to platelet aggregation, we removed the vascular endothelium from the circulation and irradiated endothelial cells in vitro. In this system, we studied the mechanisms by which ionizing radiation induced translocation of P-selectin by using immunofluorescence of human umbilical vein endothelial cells (HUVEC) and confocal microscopy. Prior to irradiation, P-selectin is localized in cytoplasmic reservoirs of HUVEC. After irradiation of HUVEC, P-selectin was translocated to the cell membrane, where it remained tethered. The lowest dose at which we could expect translocation of P-selectin to the cell membrane was 2 Gy. To determine whether P-selectin in Weibel-Palade bodies requires microtubule-dependent membrane transport, we added two microtubule-depolymerizing agents, Colcemid and nocodazole. Microtubule-depolymerizing agents prevented radiation-induced trans- location of P-selectin to the cell membrane. Thus P-selectin accumulates in irradiated blood vessels through both platelet aggregation and microtubule-dependent exocytosis of storage reservoirs within the vascular endothelium.
A General Synthesis of 1-(Dialkylaminomethyl)indoles (1998)

1-(N,N-Dialkylamino)methylindoles are prepared from the corresponding 1-(dialkylaminomethyl)benzotriazoles by treatment with indole and base. The aminoalkylation proceeds in high yield with good regioselectivity.
Low expression of S100P associated with paclitaxel resistance in ovarian cancer cell line (2008)

Low S100P expression contributes to drug resistance to paclitaxel in ovarian cancer cell lines. S100P expression thus might be a marker that can predict the effectiveness of paclitaxel based chemotherapy. Such a marker could be helpful in improving individual medication regimens for ovarian cancer patients.
Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms (1994)

Two isoforms of glutamic acid decarboxylase (GAD67 and GAD65) and their mRNAs were localized in the rat brain by immunohistochemistry and nonradioactive in situ hybridization methods with digoxigenin-labeled cRNA probes. In most brain regions, both GAD isoforms were present in neuronal cell bodies as well as axon terminals. A few populations of neurons, such as those in the reticular nucleus of the thalamus, exhibited similar cell body labeling for both GADs. However, in many brain regions, the cell bodies that were immunoreactive for GAD67 were often more numerous than those that were immunoreactive for GAD65. In contrast, the density (quantity) of GAD65-immunoreactive axon terminals was higher than that of GAD67-immunoreactive terminals. Strong parallels were observed between the intensity of immunohistochemical labeling of cell bodies and the levels of mRNA labeling for both GAD isoforms. Many groups of GAD-containing cell bodies were distinctly labeled for GAD67, and these same groups of neurons were heavily labeled for GAD67 mRNA. Such neurons included Purkinje cells of the cerebellar cortex, nonpyramidal cells in the cerebral cortex, and neurons of the reticular nucleus of the thalamus. Similar parallels in labeling were observed for GAD65 and its mRNA. Distinct cell body labeling for the protein and associated high levels of GAD65 mRNA were found in neurons of the reticular nucleus of the thalamus and periglomerular cells in the olfactory bulb. However, many cell bodies were not readily labeled for GAD65 with immunohistochemical methods. Such absence or weakness of cell body labeling for the protein was associated with low or moderate levels of GAD65 mRNA. Even though light cell body staining was frequently observed for GAD65 and its mRNA, strong axon terminal labeling for GAD65 was present. Thus, in the deep cerebellar nuclei to which the Purkinje cells of the cerebellar cortex project, strong terminal labeling was observed for both GAD isoforms even though only light cell body labeling of the Purkinje cells was obtained for GAD65 and its mRNA. The findings suggest that the two isoforms of GAD are present in most classes of GABA neurons but that they are not similarly distributed within the neurons. GAD67 is present in readily detectable amounts in many GAD-containing cell bodies whereas GAD65 is particularly prominent in many axon terminals. In addition, neurons that express either form of GAD mRNA also express the corresponding protein. Levels of labeling for the GAD mRNAs suggest that, under normal conditions, the synthesis of GAD65 is frequently lower than that of GAD67.(ABSTRACT TRUNCATED AT 400 WORDS)
Glutamic and Aspartic Anhydrides. Rearrangement of N-Carboxyglutamic 1,5-Anhydride to the Leuchs' Anhydride and Conversion of the Latter to Pyroglutamic Acid (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGlutamic and Aspartic Anhydrides. Rearrangement of N-Carboxyglutamic 1,5-Anhydride to the Leuchs' Anhydride and Conversion of the Latter to Pyroglutamic AcidJ. Kovacs, H. Nagy. Kovacs, and R. BallinaCite this: J. Am. Chem. Soc. 1963, 85, 12, 1839–1844Publication Date (Print):June 1, 1963Publication History Published online1 May 2002Published inissue 1 June 1963https://pubs.acs.org/doi/10.1021/ja00895a033https://doi.org/10.1021/ja00895a033research-articleACS PublicationsRequest reuse permissionsArticle Views865Altmetric-Citations25LEARN 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
Differences in Foot and Forearm Skin Microcirculation in Diabetic Patients With and Without Neuropathy (1998)

In healthy subjects, the endothelial-dependent and endothelial-independent vasodilatation is lower at the foot level when compared to the forearm, and a generalized impairment of the microcirculation in diabetic patients with neuropathy preserves this forearm-foot gradient. These changes may be a contributing factor for the early involvement of the foot with neuropathy when compared to the forearm.
Essays on the Facial Nerve: Part I. Microanatomy (2010)

Diversity of facial nerve anatomy is recognized and documented. Specific anatomical relationships are clarified and demonstrated as a guiding map.
The AC photovoltaic module (1996)

This paper describes the design, development and performance of a large-area photovoltaic module whose electrical output is AC power suitable for direct connection to the utility grid. The AC PV module, developed with support from the US DOE and NREL under the PV:BONUS Program, incorporates a dedicated, integrally mounted, high-efficiency 250 Watt DC-to-AC inverter that is fully compatible with 120 V, 60 Hz utility power. We call this concept an AC photovoltaic module or in context, simply an AC Module. Because of its ease of use and wide appeal, the AC PV module may be considered the first photovoltaic appliance. The module's output may be connected directly to a building's conventional AC distribution system without need for DC wiring, string combiners, DC ground-fault protection or additional power-conditioning equipment. The AC module has the potential to become the first photovoltaic power "building product", as it can be marketed as a complete, packaged solution for the emerging residential rooftop and commercial demand-side management markets.
Modeling of 2D Objects with Weighted-Quadratic Trigonometric Spline (2016)

An imperative scheme is adopted to model 2D objects by constructing a weighted-spline using a quadratic trigonometric function with well controlled shape influences of parameters. The curve models, constructed through the suggested scheme, own the best possible geometric properties such as convex hull, partition of unity, affine invariance and variation diminishing. The illustration of the method is supportive for various shape effects using interval tension property. The proposed C <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup> spline method is modest overall.
Molecular dissection of the miR-17-92 cluster's critical dual roles in promoting Th1 responses and preventing inducible Treg differentiation (2011)

Mir-17-92 encodes 6 miRNAs inside a single polycistronic transcript, the proper expression of which is critical for early B-cell development and lymphocyte homeostasis. However, during the T-cell antigen response, the physiologic function of endogenous miR-17-92 and the roles of the individual miRNAs remain elusive. In the present study, we functionally dissected the miR-17-92 cluster and revealed that miR-17 and miR-19b are the key players controlling Th1 responses through multiple coordinated biologic processes. These include: promoting proliferation, protecting cells from activation-induced cell death, supporting IFN-γ production, and suppressing inducible regulatory T-cell differentiation. Mechanistically, we identified Pten (phosphatase and tensin homolog) as the functionally important target of miR-19b, whereas the function of miR-17 is mediated by TGFβRII and the novel target CREB1. Because of its vigorous control over the Th1 cell-inducible regulatory T cell balance, the loss of miR-17-92 in CD4 T cells results in tumor evasion. Our results suggest that miR-19b and miR-17 could be harnessed to enhance the efficacy of T cell-based tumor therapy.
Inflammatory cells and mediators in bronchial lavage of patients with chronic obstructive pulmonary disease (1998)

Cigarette smoking is the most important cause of chronic obstructive pulmonary disease (COPD). Although the precise sequence of events that leads a smoker to experience airway obstruction is not completely clear, airway inflammation is a relevant factor. To investigate airway inflammation, 12 nonatopic smoking COPD patients with a forced expiratory volume in one second (FEV1) < or = 75% predicted and 10 normal nonsmoking subjects (NS) were studied with bronchoscopy and bronchial lavage (BL). Serum immunoglobulin (Ig)E levels of COPD patients correlated with the smoking history (r=0.7, p=0.008). In BL of COPD patients there was an increase of neutrophils (median, range) (COPD 62.6x10(3), 1.2-323, NS 1.35, 0-19.2, p=0.001), eosinophils (COPD 1.6, 0-6.9, NS 0.15, 0-3.7, p=0.035), the levels of interleukin (IL)-8 (COPD 1079 pg x mL(-1), 121-2,500, NS 20.4, 7.2-59, p=0.001), myeloperoxidase (MPO) (COPD 752 microg x L(-1), 11-5,500, NS 22.1, 8-70, p=0.001) and eosinophil cationic protein (ECP) (COPD 21.5 microg x L(-1), 1.8-161, NS 2, 1.8-4.9, p=0.001). Significant correlations were found in BL of COPD patients between IL-8 and neutrophils (p=0.02), MPO and neutrophils (p=0.02), IL-8 and MPO (p=0.0001) and ECP and eosinophils (p=0.02). In addition, the ratios between the BL levels of MPO and the number of neutrophils and between ECP levels and eosinophils were higher in COPD patients than in NS (p=0.03 and 0.01, respectively). These data suggest that cigarette smoke is associated with increased amounts of airway interleukin-8, a chemotactic factor for neutrophils and eosinophils. Recruited neutrophils and eosinophils are activated and they release increased amounts of inflammatory mediators capable of damaging the bronchial tissue.
Access control with IBM Tivoli access manager (2003)

Web presence has become a key consideration for the majority of companies and other organizations. Besides being an essential information delivery tool, the Web is increasingly being regarded as an extension of the organization itself, directly integrated with its operating processes. As this transformation takes place, security grows in importance. IBM Tivoli Access Manager offers a shared infrastructure for authentication and access management, technologies that have begun to emerge in the commercial marketplace. This paper describes the Authorization Service provided by IBM Tivoli Access Manager for e-business (AM) and its use by AM family members as well as third-party applications. Policies are defined over a protected object namespace and stored in a database, which is managed via a management console and accessed through an Authorization API. The protected object namespace abstracts from heterogeneous systems and thus enables the definition of consistent policies and their centralized management. ACL inheritance and delegated management allow these policies to be managed efficiently. The Authorization API allows applications with their own access control requirements to decouple authorization logic from application logic. Policy checking can be externalized by using either a proxy that sits in front of the Web servers and application servers or a plug-in that examines the request. Thus, AM familiy members establish a single entry point to enforce enterprise policies that regulate access to corporate data.
Phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of LBH589A: A novel histone deacetylase inhibitor (2004)

3025 Background: LBH589A is a novel histone deacetylase inhibitor which inhibits HDAC enzyme activity, activates p21 and inhibits proliferation of tumor cell lines at nanomolar concentrations. Methods: In this phase I trial, LBH589A was administered IV as a 30-minute infusion either on days 1–3 and 8–10 of a 21 day cycle (arm 1) or on days 1–3 and 15–17 of a 28 day cycle (arm 2). Results: Thirteen pts. (median age: 64.3 years; 10M, 3F) have been treated. Tumor types: renal cell (4 pts), NSCLC (2 pts), sarcoma (2 pts), hepatocellular (1 pt), colon (1 pt), others (3 pts). In arm 1, 11 pts. have been treated at dose levels (mg/m2): 1.2 (2 pts), 2.4 (3 pts), 4.8 (3 pts), 7.2 (3 pts). In arm 2, two pts. have been treated at dose levels: 2.4 (1 pt), 4.8 (1 pt). Performance status: 0 (3 pts), 1 (10 pts). One DLT (prolonged G2 thrombocytopenia) has been observed at the 7.2 mg/m2 dose level in arm 1. Other toxicities (all cycles): G3 neutropenia (1 pt), G3 hypoglycemia (1 pt), G2 thrombocytopenia (2 pts), and G2 anemia (2 pts). No abnormalities observed in >100 ECGs. Six of 13 pts. have exhibited stable disease (range 2–8 cycles, tumors: renal (3 pts), sarcoma (1 pt), NSCLC (1 pt), hepatocellular (1 pt)). To determine if LBH589A increases histone acetylation, Western blots were performed on total cell lysates from peripheral blood lymphocytes. Increased acetylation was observed in 1 of 2 pts. at 2.4 mg/m2 and in 2 of 3 pts. at 4.8 mg/m2 up to 24 hrs after the third dose. Onset of acetylation was rapid (1h) and, in 1 patient at 4.8 mg/m2 dose, lasted up to 7 days after the first dose. PK samples were collected on days 1 and 3 of cycle 1 and analyzed using a noncompartmental analysis. Plasma LBH589A concentrations were determined using HPLC/MS/MS assay. AUC increased proportionally with dose and mean AUCs (0–24h) were 37.7, 85.8 and 151.1 ng.h/mL, respectively, for 1.2, 2.4 and 4.8 mg/M2 dose levels on Day 3. Terminal half-life was approximately 15–20 hrs. Conclusions: In this phase I study, LBH589A given IV appears to be well tolerated with consistent PD effects. Additional evaluation is continuing at the 7.2 mg/m2 dose level for arm 1 and at the 9.6 mg/m2 dose level a for arm 2. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis; Novartis Germany Novartis Novartis Novartis