gebhart/patrepeval huggingface dataset:
Interleukin-4, -5, and -6 and Tumor Necrosis Factor-α in Normal and Asthmatic Airways: Evidence for the Human Mast Cell as a Source of these Cytokines (1994)

Asthma is characterized by the presence of an inflammatory cell infiltrate in the bronchial mucosa consisting of activated mast cells, eosinophils, and T cells. Several cytokines are considered to play a pivotal role in this response, particularly interleukin (IL)-4, IL-5, IL-6, and tumor necrosis factor-alpha (TNF-alpha). In this study, we have used immunohistochemistry applied to thin glycol methacrylate sections of bronchial mucosal biopsies to define the cellular provenance of these cytokines in normal and asthmatic airways. Both the asthmatic and normal mucosa contained numerous cells staining positively for all four cytokines, with the majority identified as mast cells by their tryptase content. Eosinophils also accounted for some IL-5 immunostaining in the asthmatic biopsies. By using two monoclonal antibodies directed to different epitopes of IL-4, we provide tentative evidence for enhanced IL-4 secretion in asthma. Similarly, a sevenfold increase in the number of mast cells staining for TNF-alpha in the asthmatic biopsies suggests that this cytokine is also up-regulated in this disease. These findings clearly identify human mast cells as a source of IL-4, IL-5, IL-6, and TNF-alpha and add to the view that, along with T cells, mast cells may play an important role in initiating and maintaining the inflammatory response in asthma.
HLA class II antigen expression in human papillomavirus-associated cervical cancer. (1992)

The observation that tumor cells of some neoplasms display major histocompatibility complex (MHC) class II molecules may be of functional significance, influencing the progression of malignancy by allowing the cancer cells to present antigen to the immune system. In the normal cervix, class II molecules are expressed by columnar but not squamous epithelium. The pattern of MHC class II expression in cervical carcinomas has been documented using immunohistochemical methods. Of 53 cervical squamous carcinomas examined for MHC class II expression, only 17% maintained a negative phenotype characteristic of the epithelium from which they were derived, while the remaining tumors exhibited either uniform (45%) or heterogeneous (38%) expression. Tumor areas which were class II positive also express class II associated invariant chain and the adhesion molecules lymphocyte function antigen 3 and intercellular adhesion molecule 1. The DR, DP, and DQ class II MHC subloci are differentially expressed, suggesting independent regulation. There is a trend for tumors with the uniform class II phenotype to predominantly express DR antigen, whereas tumors of the heterogeneous class II phenotype express with equal frequency either DR or DP antigens dominantly. There is no apparent influence of class II status on lymphocyte infiltration of the tumors. The presence of human papillomavirus 16 DNA in the cervical carcinoma specimens was analyzed by Southern blotting of restriction enzyme digested DNA and no correlation between the presence of human papilloma virus and MHC class II expression was found.
Sams teach yourself Visual Basic 6 in 21 days (1998)

From the Publisher:
In just 21 days, you'll have all the skills you need to develop 32-bit programs for Windows. With this complete tutorial, you'll master the basics and then move on to the more advanced features and concepts. Understand the fundamentals of rapid application development. Master all of the new and advanced features that Visual Basic 6 offers. Learn how to effectively use the latest tools by following effective, real-world examples. This book is designed for the way you learn. Go chapter by chapter through the step-by-step lessons or just choose those lessons that interest you the most.
Mapping quantitative trait loci with extreme discordant sib pairs: sampling considerations. (1996)

Elsewhere we have proposed the use of extreme discordant sib pairs (EDSPs) for mapping quantitative trait loci in humans. Here we present sample sizes necessary to achieve a given level of power with this study design, as well as the number of sibs that need to be screened to obtain the required sample. Further, we present simple formulas for adjusting sample sizes to account for variable significance levels and power, as well as the density and informativeness of linkage markers in a multipoint sib-pair analysis. We conclude that with EDSPs, the most powerful study design, the smallest genetic effect detectable with a realistic sample size is approximately 10% of the variance of the trait.
Population pharmacokinetics of ustekinumab in patients with active psoriatic arthritis (2010)

The pharmacokinetics of ustekinumab in patients with PsA are comparable to those in patients with moderate-to-severe plaque psoriasis which was previously investigated.
Therapeutic Peptide Nucleic Acids: Principles, Limitations, and Opportunities. (2017)

Since their invention in 1991, peptide nucleic acids (PNAs) have been used in a myriad of chemical and biological assays. More recently, peptide nucleic acids have also been demonstrated to hold great potential as therapeutic agents because of their physiological stability, affinity for target nucleic acids, and versatility. While recent modifications in their design have further improved their potency, their preclinical development has reached new heights due to their combination with recent advancements in drug delivery. This review focuses on recent advances in PNA therapeutic applications, in which chemical modifications are made to improve PNA function and nanoparticles are used to enhance PNA delivery.
Genetic analysis of IDDM: The GAW5 multiplex family dataset (1989)

In a collaborative effort by 12 centers from Europe and North America, data were assembled from 94 multiplex families with insulin-dependent diabetes mellitus (IDDM) for analysis of genetic and other factors of possible etiological importance. The dataset contains information on the following genetic markers: HLA-DR beta and -DQ beta restriction fragment length polymorphisms (RFLPs), three RFLPs detected with two probes that map 5' to the insulin gene, the serologically defined HLA loci, and the immunoglobulin allotypes. Data also were included for auto-antibodies to insulin and pancreatic islet cells as possible indicators of pathogenesis and for antibodies to certain viruses that have been implicated as "triggering" agents in IDDM. Medical history of family members was obtained by means of a uniform questionnaire. Identical copies of the dataset were distributed to anyone wishing to participate in the analysis for the IDDM component of GAW5. The multiplex IDDM family dataset is now available on request for further analysis.
Medical diagnosis with c4.5 rule preceded by artificial neural network ensemble (2003)

Comprehensibility is very important for any machine learning technique to be used in computer-aided medical diagnosis. Since an artificial neural network ensemble is composed of multiple artificial neural networks, its comprehensibility is worse than that of a single artificial neural network. In this paper, C4.5 Rule-PANE which combines artificial neural network ensemble with rule induction by regarding the former as a preprocess of the latter, is proposed. At first, an artificial neural network ensemble is trained. Then, a new training data set is generated by feeding the feature vectors of the original training instances to the trained ensemble and replacing the expected class labels of the original training instances with the class labels output from the ensemble. Additional training data may also be appended by randomly generating feature vectors and combining them with their corresponding class labels output from the ensemble. Finally, a specific rule induction approach, i.e., C4.5 Rule, is used to learn rules from the new training data set. Case studies on diabetes, hepatitis, and breast cancer show that C4.5 Rule-PANE could generate rules with strong generalization ability, which profits from artificial neural network ensemble, and strong comprehensibility, which profits from rule induction.
Biosynthesis of an Endogenous Cannabinoid Precursor in Neurons and its Control by Calcium and cAMP (1996)

Understanding the mechanisms involved in the biogenesis of N-arachidonoylethanolamine (anandamide) and N-palmitoylethanolamine is important in view of the possible role of these lipids as endogenous cannabinoid substances. Anandamide (which activates cannabinoid CB1 receptors) and N-palmitoylethanolamine (which activates a CB2-like receptor subtype in mast cells) may both derive from cleavage of precursor phospholipid, N-acylphosphatidylethanolamine (NAPE), catalyzed by Ca(2+)-activated D-type phosphodiesterase activity. We report here that the de novo biosynthesis of NAPE is enhanced in a Ca(2+)-dependent manner when rat cortical neurons are stimulated with the Ca(2+)-ionophore ionomycin or with membrane-depolarizing agents such as veratridine and kainate. This reaction is likely to be mediated by a neuronal N-acyltransferase activity, which catalyzes the transfer of an acyl group from phosphatidylcholine to the ethanolamine moiety of phosphatidylethanolamine. In addition, we show that Ca2+-dependent NAPE biosynthesis is potentiated by agents that increase cAMP levels, including forskolin and vasoactive intestinal peptide. Our results thus indicate that NAPE levels in cortical neurons are controlled by Ca2+ ions and cAMP. Such regulatory effect may participate in maintaining a supply of cannabimimetic N-acylethanolamines during synaptic activity, and prime target neurons for release of these bioactive lipids.
The transforming potential of the c-erbB-2 protein is regulated by its autophosphorylation at the carboxyl-terminal domain. (1991)

The mutant c-erbB-2 protein with Glu instead of Val-659 exhibited transforming activity in NIH 3T3 cells. This protein showed enhanced tyrosine kinase activity in vitro and enhanced autophosphorylation at Tyr-1248 located proximal to the carboxyl terminus. Enhanced tyrosine phosphorylation of several cellular proteins was detected in cells expressing the Glu-659 c-erbB-2 protein. Introduction of an additional mutation at the ATP-binding site (Lys-753 to Met) of this protein resulted in abolition of its transforming ability. These data indicate that the transforming potential of c-erbB-2 is closely correlated with elevated tyrosine kinase activity of the gene product. To investigate the role of autophosphorylation in cell transformation, we introduced an additional mutation at the autophosphorylation site of the Glu-659 c-erbB-2 protein (Tyr-1248 to Phe). This mutant protein exhibited lower tyrosine kinase activity and lower transforming activity. On the other hand, when the carboxyl-terminal 230 amino acid residues were deleted from the c-erbB-2 protein, the tyrosine kinase activity and cell-transforming activity of the protein were enhanced. Thus, the carboxyl-terminal domain, which contains the major autophosphorylation site, Tyr-1248, may regulate cellular transformation negatively and autophosphorylation may eliminate this negative regulation.
Nonlinear Optical Properties of Proteins Measured by Hyper-Rayleigh Scattering in Solution (1993)

Hyper-Rayleigh scattering has been used to determine the nonlinear optical properties of a chromophore-containing protein in solution. Because the technique of hyper-Rayleigh scattering allows the measurement of hyperpolarizabilities in an isotropic solution without the application of an electric field, this method is ideally suited for the study of proteins that carry a net charge. The observed orientational correlation between the nonlinear optical chromophores in incompletely solubilized protein molecules suggests that guidelines from protein structures can be used for the engineering of supramolecular structures with high optical nonlinearity.
Identification of a Fusobacterium nucleatum 65 kDa serine protease (2004)

A 65 kDa protease was partially purified from extracellular vesicles of Fusobacterium nucleatum cultures by preparative SDS-PAGE followed by electroelution. The pH optimum of the protease is 7.5-8.0 and its activity could be inhibited by serine protease inhibitors. The protease was found to degrade the extracellular matrix proteins fibrinogen and fibronectin as well as collagen I and collagen IV which were degraded at 37 degrees C but not at 28 degrees C, indicating the presence of a gelatinase activity in these bacteria. The 65 kDa protease was also able to digest the alpha-chains of immunoglobulin A but not immunoglobulin G. The 65 kDa F. nucleatum protease, capable of degrading native proteins, may play an important role in both the nutrition and pathogenicity of these periodontal microorganisms. The degradation of extracellular matrix proteins by bacterial enzymes may contribute to the damage of periodontal tissues, and degradation of IgA may help the evasion of the immune system of the host by the bacteria.
Modeling Alzheimer’s disease in transgenic rats (2013)

Alzheimer's disease (AD) is the most common form of dementia. At the diagnostic stage, the AD brain is characterized by the accumulation of extracellular amyloid plaques, intracellular neurofibrillary tangles and neuronal loss. Despite the large variety of therapeutic approaches, this condition remains incurable, since at the time of clinical diagnosis, the brain has already suffered irreversible and extensive damage. In recent years, it has become evident that AD starts decades prior to its clinical presentation. In this regard, transgenic animal models can shed much light on the mechanisms underlying this "pre-clinical" stage, enabling the identification and validation of new therapeutic targets. This paper summarizes the formidable efforts to create models mimicking the various aspects of AD pathology in the rat. Transgenic rat models offer distinctive advantages over mice. Rats are physiologically, genetically and morphologically closer to humans. More importantly, the rat has a well-characterized, rich behavioral display. Consequently, rat models of AD should allow a more sophisticated and accurate assessment of the impact of pathology and novel therapeutics on cognitive outcomes.
Reaktionen von 3‐(Dimethylamino)‐2H‐azirinen mit 1,3‐Benzoxazol‐2(3H)‐thion (1990)

Reaction of 3‐(Dimethylamino)‐2 H ‐azirines with 1,3‐Benzoxazole‐2(3 H )‐thione The reaction of 3‐(dimethylamino)‐2 H ‐azirines 2 with 1,3‐benzoxazole‐2(3 H )‐thione ( 5 ), which can be considered as NH‐acidic heterocycle (p K a ca. 7.3), in MeCN at room temperature, leads to 3‐(2‐hydroxyphenyl)‐2‐thiohydantoins 6 and thiourea derivatives of type 7 ( Scheme 2 ). A reaction mechanism for the formation of the products via the crucial zwitterionic intermediate A ′ is suggested. This intermediate was trapped by methylation with Mel and hydrolysis to give 9 ( Scheme 4 ). Under normal reaction conditions, A ′ undergoes a ring opening to B which is hydrolyzed during workup to yield 6 or rearranges to give the thiourea 7. A reasonable intermediate of the latter transformation is the isothiocyanate E ( Scheme 3 ) which also could be trapped by morpholine. In i‐PrOH at 55–65° 2a and 5 react to yield a mixture of 6a , 2‐(isopropylthio)‐1,3‐benzoxazole ( 12 ), and the thioamide 13 ( Scheme 5 ). A mechanism for the surprising alkylation of 5 via the intermediate 2‐amino‐2‐alkoxyaziridine F is proposed. Again via an aziridine, e.g. H ( Scheme 6 ), the formation of 13 can be explained.
Illustrated Genera of Ascomycetes (1990)

Illustrated genera of ascomycetes , Illustrated genera of ascomycetes , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Kinetic analysis of the nonenzymatic glycosylation of hemoglobin. (1981)

The rate constants have been derived for (a) the condensation of glucose with hemoglobin to form the labile Schiff base intermediate, pre-AIc; (b) the dissociation of this complex to hemoglobin and glucose; (c) the rearrangement of this complex to form the stable ketoamine, Hb AIc. These measurements required the purification of commercially available D-[14C]glucose in order to remove a rapidly reacting contaminant. The initial condensation reaction rate (kappa'1) was measured by incubating column purified Hb A0 for up to 8 h under physiologic conditions with purified D-[14C]glucose in the presence of cyanoborohydride which traps the Schiff base and reduces it to a stable adduct. A parallel incubation utilizing Hb AIc revealed the contribution of the beta-NH2-terminal amino group (kappa 1) to the overall value for kappa'1. The reverse reaction rate (kappa -1) was determined from incubations carried ut in the absence of cyanoborohydride. The rate of the Amadori rearrangement (kappa 2) was determined from longer (6-21 days) incubations under identical conditions, followed by chromatographic isolation of Hb AIc. This value for kappa 2 agrees well with one we previously obtained from in vivo data. These experiments provide direct chemical evidence for an aldimine precursor in the nonenzymatic glycosylation of protein. Furthermore, the use of these rate constants provides a reasonable estimate of the distribution of the labile aldimine (pre-AIc) and the stable ketoamine (Hb AIc) in normal and diabetic red cells. This information is useful in the interpretation of measurements of glycosylated hemoglobin in diabetic patients.
Differential mediator release from basophils of allergic and non‐allergic asthmatic patients after stimulation with anti‐IgE and C5a (2001)

The differentiation between allergic and non-allergic asthma is a common and important challenge for the clinician. Until now, no in vitro diagnostic characteristics have been described to distinguish between these types. To examine the diagnostic value of a basophil stimulation test, we compared anti-IgE- and C5a-induced mediator release from peripheral blood leucocytes in different types of bronchial asthma. Peripheral blood leucocytes (PBL) from 10 aspirin-sensitive asthmatics (ASA), 12 non-allergic asthmatics without aspirin intolerance (NAA), seven allergic asthmatics (AA), and nine healthy controls were prepared by dextran sedimentation. After priming with interleukin-3 (IL-3) PBL were stimulated with anti-IgE and C5a, and the release of histamine (HR) and sulfidoleukotrienes (LTR) in the supernatant was compared. Additionally, purified leucocyte fractions were studied to determine the cellular source of mediator release. Upon stimulation with anti-IgE LTR was slightly, but not significantly, lower in ASA and NAA compared to AA and controls. In contrast, C5a-triggered LTR was significantly higher in ASA (14.4 +/- 12.88 pg/105 cells) and NAA (22.9 +/- 22.61 pg/105 cells) than in AA (9.6 +/- 3.29 pg/105 cells) and controls (7.5 +/- 7.19 pg/105 cells) (P < 0.05). This difference between ASA and NAA vs. AA and controls was even more pronounced when determining the quotient C5a-/anti-IgE-induced LTR (P < 0.001). At an optimal cut-off point of 1.0, calculated by relative operating characteristics (ROC) analysis, the positive predictive value for a donor to belong to ASA or NAA was 0.94. No significant differences could be found in HR between the asthmatic patient groups and healthy controls in either condition. As cellular source of LTR and HR the basophil could be determined. Determination of anti-IgE- and C5a-induced LTR from basophils allows us to discriminate between allergic and non-allergic asthmatic patients. For diagnostic purposes the quotient C5a-/anti-IgE-induced LTR is more significant than considering a single parameter. ASA cannot be distinguished from NAA.
A four-quadrant NMOS analog multiplier (1982)

A four-quadrant NMOS analog multiplier, which achieves linearity better than 0.3 percent at 75 percent of full-scale swing, a bandwidth of DC to 1.5 MHz, and output noise 77 dB below full scale is described. Active area is 450 mils/SUP 2/.
Minimizing a binding domain from protein A. (1996)

We present a systematic approach to minimizing the Z-domain of protein A, a three-helix bundle (59 residues total) that binds tightly (Kd = 10 nM) to the Fc portion of an immunoglobin IgG1. Despite the fact that all the contacts seen in the x-ray structure of the complex with the IgG are derived from residues in the first two helices, when helix 3 is deleted, binding affinity is reduced > 10(5)-fold (Kd > 1 mM). By using structure-based design and phage display methods, we have iteratively improved the stability and binding affinity for a two-helix derivative, 33 residues in length, such that it binds IgG1, with a Kd of 43 nM. This was accomplished by stepwise selection of random mutations from three regions of the truncated Z-peptide: the 4 hydrophobic residues from helix 1 and helix 2 that contacted helix 3 (the exoface), followed by 5 residues between helix 1 and helix 2 (the intraface), and lastly by 19 residues at or near the interface that interacts with Fc (the interface). As selected mutations from each region were compiled (12 in total), they led to progressive increases in affinity for IgG, and concomitant increases in alpha-helical content reflecting increased stabilization of the two-helix scaffold. Thus, by sequential increases in the stability of the structure and improvements in the quality of the intermolecular contacts, one can reduce larger binding domains to smaller ones. Such mini-protein binding domains are more amenable to synthetic chemistry and thus may be useful starting points for the design of smaller organic mimics. Smaller binding motifs also provide simplified and more tractable models for understanding determinants of protein function and stability.
Identification, isolation, and characterization of daintain (allograft inflammatory factor 1), a macrophage polypeptide with effects on insulin secretion and abundantly present in the pancreas of prediabetic BB rats (1997)

A bioactive macrophage factor, the polypeptide daintain/allograft inflammatory factor 1 (AIF1), has been isolated from porcine intestine. It was discovered when searching for intestinal peptides with effects on insulin release, and its purification was monitored by the influence of the peptide fractions on pancreatic glucose-induced insulin secretion. Daintain/AIF1 is a 146-aa residue polypeptide with a mass of 16,603 Da and an acetylated N terminus. An internal 44-residue segment with the sequence pattern -KR-KK-GKR- has a motif typical of peptide hormone precursors, i.e., dibasic sites for potential activation cleavages and at the sequentially last such site, the structure GKR. The latter is a signal for C-terminal amide formation in the processing of peptide hormones. Daintain/AIF1 is immunohistochemically localized to microglial cells in the central nervous system and to dendritic cells and macrophages in several organs. A particularly dense accumulation of daintain/AIF1-immunoreactive macrophages was observed in the insulitis affecting the pancreatic islets of prediabetic BB rats. When injected intravenously in mice, daintain/AIF1 at 75 pmol/kg inhibited glucose (1 g/kg)-stimulated insulin secretion, with a concomitant impairment of the glucose elimination, whereas at higher doses (7.5 and 75 nmol/kg), daintain/AIF1 potentiated glucose-stimulated insulin secretion and enhanced the glucose elimination. Its dual influence on insulin secretion in vivo at different peptide concentrations, and the abundance of macrophages expressing daintain/AIF1 in the pancreatic islets of prediabetic rats, suggest that daintain/AIF1 may have a role in connection with the pathogenesis of insulin-dependent diabetes mellitus.
p53 protein expression in central nervous system neoplasms. (1992)

The use of sophisticated gene amplification techniques or highly sensitive immunohistochemical methods might be useful in distinguishing between reactive and neoplastic astrocytic lesions, and in the identification of malignant progression in other non-astrocytic glial tumours. Tumours with very similar histogenetic differentiation features might actually be a genetically heterogeneous group with possible different clinical courses.