gebhart/patrepeval huggingface dataset:
Chimeric Co-stimulatory Molecules That Selectively Act through CD28 or CTLA-4 on Human T Cells (2002)

CD28 and CTLA-4 (CD152) play a pivotal role in the regulation of T cell activation. Upon ligation by CD80 (B7-1) or CD86 (B7-2), CD28 induces T cell proliferation, cytokine production, and effector functions, whereas CTLA-4 signaling inhibits expansion of activated T cells and induces tolerance. Therefore, we hypothesized that co-stimulatory molecules that preferentially bind CD28 or CTLA-4 would have dramatically altered biological properties. We describe directed molecular evolution of CD80 genes derived from human, orangutan, rhesus monkey, baboon, cat, cow, and rabbit by DNA shuffling and screening. In contrast to wild-type CD80, the evolved co-stimulatory molecules, termed CD28-binding protein (CD28BP) and CTLA-4-binding protein (CTLA-4BP), selectively bind to CD28 or CTLA-4, respectively. Furthermore, CD28BP has improved capacity to induce human T cell proliferation and interferon-gamma production compared with wild-type CD80. In contrast, CTLA-4BP inhibited human mixed leukocyte reaction (MLR) and enhanced interleukin 10 production in MLR, supporting a role for CTLA-4BP in inducing T cell anergy and tolerance. In addition, co-stimulation of purified human T cells was significantly suppressed when CTLA-4BP was cotransfected with either CD80 or CD28BP. The amino acid sequences of CD28BP and CTLA-4BP were 61 and 96% identical with that of human CD80 and provide insight into the residues that are critical in the ligand binding. These molecules provide a new approach to characterization of CD28 and CTLA-4 signals and to manipulation of the T cell response.
Sialic Acid Content of Plasminogen 2 Glycoforms as a Regulator of Fibrinolytic Activity (1995)

Six glycoforms of plasminogen 2 were isolated using a combination of lectin affinity chromatography and chromatofocussing, and the sialic acid content of each glycoform was determined. The kinetics of activation of each glycoform by tissue-type plasminogen activator were analyzed on a fibrin surface and in solution. The second-order rate constant (measured on a fibrin surface) decreased from 1.65 x 10(6) M-1 s-1 to 3.77 x 10(4) M-1 s-1 as the sialic acid content of the glycoforms increased from 1.3 mol/mol of protein to 13.65 mol/mol of protein. A similar correlation was noted for activation in solution. Each glycoform was converted to plasmin, and the inhibition constants for the reaction between alpha 2-antiplasmin and plasmin glycoforms were determined. All overall Ki values, reflecting the final essentially irreversible complex, were in the picomolar range. Sialic acid does not affect inhibition of plasmin by alpha 2-antiplasmin; however, hypersialylated plasmin does not appear to have a kringle-dependent component to inhibition.
Solid-Phase Synthesis of Oligourea Peptidomimetics Employing the Fmoc Protection Strategy (2001)

A solid-phase-Fmoc-based-synthesis strategy is described for oligourea peptidomimetics as well as a convenient general synthesis approach for the preparation of the required building blocks 5a-j and 5k. These are suitable for use in peptide or robot synthesizers, which is illustrated by the synthesis of oligourea peptidomimetics of part of Leu-enkephalin (10) and a neurotensin derivative (17).
Improved targeting of miRNA with antisense oligonucleotides (2006)

MicroRNAs (miRNAs) are a class of 20-24 nt noncoding RNAs that regulate target mRNAs post-transcriptionally by binding with imperfect complementarity in the 3'-untranslated region (3'-UTR) and inhibiting translation or RNA stability. Current understanding of miRNA biology is limited, and antisense oligonucleotide (ASO) inhibition is a powerful technique for miRNA functionalization in vitro and in vivo, and for therapeutic targeting of miRNAs. Identification of optimal ASO chemistries for targeting miRNAs is therefore of great interest. We evaluated a number of 2'-sugar and backbone ASO modifications for their ability to inhibit miR-21 activity on a luciferase reporter mRNA. ASO modifications that improved target affinity improved miRNA ASO activity, yet the positioning of high-affinity modifications also had dramatically different effects on miRNA activity, suggesting that more than affinity determined the effectiveness of the miRNA ASOs. We present data in which the activity of a modified miRNA ASO was inversely correlated to its tolerability as an siRNA passenger strand, suggesting that a similar mechanism could be involved in the dissociation of miRNA ASOs and siRNA passenger strands. These studies begin to define the factors important for designing improved miRNA ASOs, enabling more effective miRNA functionalization and therapeutic targeting.
Hormone Replacement Therapy and Risk of Breast Cancer With a Favorable Histology (1999)

Exposure to HRT was associated most strongly with an increased risk of invasive breast cancer with a favorable prognosis. These data add important clinical information for assessing the risks and benefits of HRT use.
Toward fully automated genotyping: allele assignment, pedigree construction, phase determination, and recombination detection in Duchenne muscular dystrophy. (1994)

Human genetic maps have made quantum leaps in the past few years, because of the characterization of > 2,000 CA dinucleotide repeat loci: these PCR-based markers offer extraordinarily high PIC, and within the next year their density is expected to reach intervals of a few centimorgans per marker. These new genetic maps open new avenues for disease gene research, including large-scale genotyping for both simple and complex disease loci. However, the allele patterns of many dinucleotide repeat loci can be complex and difficult to interpret, with genotyping errors a recognized problem. Furthermore, the possibility of genotyping individuals at hundreds or thousands of polymorphic loci requires improvements in data handling and analysis. The automation of genotyping and analysis of computer-derived haplotypes would remove many of the barriers preventing optimal use of dense and informative dinucleotide genetic maps. Toward this end, we have automated the allele identification, genotyping, phase determinations, and inheritance consistency checks generated by four CA repeats within the 2.5-Mbp, 10-cM X-linked dystrophin gene, using fluorescein-labeled multiplexed PCR products analyzed on automated sequencers. The described algorithms can deconvolute and resolve closely spaced alleles, despite interfering stutter noise; set phase in females; propagate the phase through the family; and identify recombination events. We show the implementation of these algorithms for the completely automated interpretation of allele data and risk assessment for five Duchenne/Becker muscular dystrophy families. The described approach can be scaled up to perform genome-based analyses with hundreds or thousands of CA-repeat loci, using multiple fluorophors on automated sequencers.
S/MIME Version 2 Message Specification (1998)

This document describes a protocol for adding cryptographic signature
and encryption services to MIME data. [STANDARDS-TRACK]
Some General Trends in the Area of Organic—Inorganic Composites (1995)

This overview chapter first reviews the sol-gel process as it is being used by ceramists, and then describes how it is being modified by the incorporation of organic materials. Six general topics involving the organic-inorganic composites resulting from these new approaches are then illustrated using examples chosen from the chapters of the present book.
Biomedical magnetic resonance imaging (1988)

The book presents a dissertation on the fundamentals of MR imaging and the principles of image formation. This is followed by chapters on surface coils and magnetopharmaceuticals. The authors report on spectroscopy and multinuclear MR imaging. The authors review current and potential clinical applications of MR imaging, including flow imaging.
Surgical procedures for reconstruction of the lower jaw using the titanium-coated hollow-screw reconstruction plate system: bridging of defects. (1987)

The various advantages rendered by the system described enable primary as well as long-term functional stability even in cases in which conventional systems would be insufficient. The evaluation of 49 cases managed in Bern and Sweden confirm the efficiency of this reconstruction system.
Functional murine interleukin 6 receptor with the intracisternal A particle gene product at its cytoplasmic domain. Its possible role in plasmacytomagenesis. (1990)

Two species of the cDNAs encoding murine IL-6-R (one is abnormal and the other authentic) have been cloned from a plasmacytoma cell line, P3U1, and BALB/c mouse spleen cDNA libraries. In the cDNA encoding the abnormal IL-6-R, the region corresponding to an intracytoplasmic domain was replaced with a part of the long terminal repeat of the intracisternal A particle gene (IAP-LTR). The authentic IL-6-R consists of 460 amino acids with the domain of the Ig superfamily. The overall homology between murine and human IL-6-R was 69 and 54% at DNA and protein levels, respectively. The extracellular domain after the Ig-like domain of murine IL-6-R was found to have an homology with those of murine erythropoietin R, human IL-2-R beta chain, murine IL-4-R, and human granulocyte-macrophage CSF-R, as in the case of human IL-6-R, and these receptors have been classified as members of the IL receptor family. In P3U1 cells, the expression of the mRNA encoding abnormal IL-6-R was much higher than that of the mRNA encoding authentic IL-6-R. An IL-6-dependent human T cell line, KT-3, which did not respond to murine IL-6, acquired the responsiveness to murine IL-6 when transfected with the cDNA encoding abnormal IL-6-R, indicating that abnormal IL-6-R lacking a normal cytoplasmic domain can function. Since IL-6 functions as a potent growth factor for murine plasmacytomas, over-expression of abnormal IL-6-R may function as a positive selection element for the development of certain plasmacytomas.
Quantitative determination of acetylsalicylic acid and acetaminophen in tablets by FT-Raman spectroscopyElectronic Supplementary Information available. See http://www.rsc.org/suppdata/an/b1/b108240j/ (2001)

A procedure for quantitative determination of acetylsalicylic acid and acetaminophen in pharmaceuticals by PLS (partial least squares) and PCR (principal component regression) treatment of FT (Fourier transform)-Raman spectroscopic data is proposed. The proposed method was tested on powdered samples. Three chemometric models were built: the first, for samples consisting of an active substance diluted by lactose, starch and talc; the second, in which a simple inorganic salt was applied as an internal standard and additions were not taken into account; and the third, in which a model was constructed for a commercial pharmaceutical, where all constituents of the tablet were known. By utilising selected spectral ranges and by changing the chemometric conditions it is possible to carry out fast and precise analysis of the active component content in medicines on the basis of the simplified chemometric models. The proposed method was tested on five commercial tablets. The results were compared with data obtained by intensity ratio and pharmacopoeial methods. To appraise the quality of the models, the relative standard error of predictions (RSEPs) were calculated for calibration and prediction data sets. These were 0.7-2.0% and 0.8-2.3%, respectively, for the different PLS models. Application of these models to the Raman spectra of commercial tablets containing acetylsalicylic acid gave RSEP values of 1.3-2.0% and a mean accuracy of 1.2-1.7% with a standard deviation of 0.6-1.2%.
Alternative endings (2008)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
VAGINAL MUCOSAL IMMUNITY BASED ON IgG-MUCIN CROSSLINKING (2019)

In this thesis, I investigated whether IgG, the predominant antibody in cervicovaginal mucus (CVM), can interact with CVM constituents to protect against Herpes Simplex Virus 1 (HSV-1) infection. Despite the weak affinity between individual IgG molecules and mucins, we hypothesize that multiple virion-bound IgG can avidly crosslink HSV-1 to the mucin mesh, thereby preventing HSV-1 from reaching the target cells. Consistent with this hypothesis, I showed that HSV-1 freely diffused through pH-neutralized CVM with low levels of anti-HSV-1 IgG, but was immobilized in samples with modest levels of endogenous or exogenously added anti-HSV-1 IgG. Removal of the Fc domain and N-glycans from IgG both markedly reduced its trapping potency. Finally, a non-neutralizing monoclonal IgG against HSV-gG provided significant protection against vaginal HSV challenges in mice, and this protection was eliminated in the absence of mucus. These results strongly suggest secreted IgG can work in tandem with mucus to block infections.
Purification and Characterization of a Thermostable Serine Protease fromBacillus thuringiensis (1989)

Journal Article Purification and Characterization of a Thermostable Serine Protease from Bacillus thuringiensis Get access Akane Kunitate, Akane Kunitate Biochemical Research Department, Toagosei Chemical Industry Co., Ltd., Minato-ku, Nagoya 455, Japan Search for other works by this author on: Oxford Academic Google Scholar Masaji Okamoto, Masaji Okamoto Biochemical Research Department, Toagosei Chemical Industry Co., Ltd., Minato-ku, Nagoya 455, Japan Search for other works by this author on: Oxford Academic Google Scholar Iwao Ohmori Iwao Ohmori Biochemical Research Department, Toagosei Chemical Industry Co., Ltd., Minato-ku, Nagoya 455, Japan Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 53, Issue 12, 1 December 1989, Pages 3251–3256, https://doi.org/10.1080/00021369.1989.10869830 Published: 01 December 1989 Article history Received: 21 June 1989 Published: 01 December 1989
Acrylamide derivatives as antiallergic agents. I. Synthesis and structure-activity relationships of N-((4-substituted 1-piperazinyl)alkyl)-3-(aryl and heteroaryl)acrylamides. (1989)

A new series of acrylamide derivatives (7-10) were synthesized. Antiallergic activity of these compounds was evaluated and their structure-activity relationships were examined. Compound 10d, N-[4-(4-diphenylmethyl-1-piperazinyl)butyl]-3-(3-pyridyl)acrylamid e, showed antiallergic activity equivalent or superior to that of ketotifen in the rat passive cutaneous anaphylaxis (PCA) test by oral administration. Compound 10d, unlike ketotifen, had more potent in vitro 5-lipoxygenase inhibitory activity than caffeic acid, whereas its in vitro antihistamine activity was weaker than that of ketotifen. In addition, its inhibitory activity against histamine release from rat mast cells was approximately two-thirds as potent as that of disodium cromoglycate (DSCG). Compound 10d is a promising agent for treating a variety of allergic diseases.
The stereotaxic retractor in computer-assisted stereotaxic microsurgery (1988)

✓ The authors describe a cylindrical retractor that is attached to a standard stereotaxic frame. This retractor provides a route for stereotaxic procedures and exposure of and a reference structure for the computer-assisted removal of deep-seated intracranial lesions defined stereotaxically by computerized tomography and magnetic resonance imaging.
SARD: A statistical approach for ranking database tuning parameters (2008)

Traditionally, DBMSs are shipped with hundreds of configuration parameters. Since the database performance highly depends on the appropriate settings of the configuration parameters, DBAs spend a lot of their time and effort to find the best parameter values for tuning the performance of the application of interest. In many cases, they rely on their experience and some rules of thumbs. However, time and effort may be wasted by tuning those parameters which may have no or marginal effects. Moreover, tuning effects also vary depending on the expertise of the DBAs, but skilled DBAs are increasingly becoming rare and expensive to employ. To address these problems, we present a statistical approach for ranking database parameters (SARD), which is based on the Plackett & Burman statistical design methodology. SARD takes the query workload and the number of configuration parameters as inputs, and using only a linear number of experiments, generates a ranking of database parameters based on their relative impacts on the DBMS performance. Preliminary experimental results using TPC-H and PostgreSQL show that SARD generated ranking can correctly identify critical configuration parameters.
Natural Polyphenols Inhibit Lysine-Specific Demethylase-1 in vitro. (2013)

Natural polyphenols, such as resveratrol, have beneficial functions on major human diseases such as cancer, diabetes, and cardiovascular disease. Besides acting as antioxidants, some of these polyphenols can also target proteins to modulate specific biological pathways. The lysine-specific histone demethylase LSD1 plays important roles in cell growth, differentiation and nutrient metabolism. Here, we studied the effect of natural polyphenols resveratrol, curcumin, quercetin and analogs on LSD1. Using <i>in vitro</i> LSD1 enzymatic assays, we show that resveratrol, curcumin and quercetin displayed a potent inhibitory effect on the LSD1 activity and were more potent than the known LSD1 inhibitor trans-2-phenylcyclopropylamine (TCP). The new function of resveratrol, curcumin and quercetin is independent of their antioxidant properties, as other antioxidants had no effect on LSD1 under the similar conditions. In C2C12 fibroblasts, resveratrol and curcumin can efficiently inhibit myogenic expression and differentiation, for which LSD1 is required. Thus, our study has identified LSD1 as a novel target of bioactive natural compounds, such as resveratrol, curcumin and quercetin, and such finding suggests that LSD1 inhibition can at least partially contribute to some of the previously observed beneficial effects of these compounds.
MicroRNA-302 Increases Reprogramming Efficiency via Repression of NR2F2 (2012)

MicroRNAs (miRNAs) have emerged as critical regulators of gene expression through translational inhibition and RNA decay and have been implicated in the regulation of cellular differentiation, proliferation, angiogenesis, and apoptosis. In this study, we analyzed global miRNA and mRNA microarrays to predict novel miRNA-mRNA interactions in human embryonic stem cells and induced pluripotent stem cells (iPSCs). In particular, we demonstrate a regulatory feedback loop between the miR-302 cluster and two transcription factors, NR2F2 and OCT4. Our data show high expression of miR-302 and OCT4 in pluripotent cells, while NR2F2 is expressed exclusively in differentiated cells. Target analysis predicts that NR2F2 is a direct target of miR-302, which we experimentally confirm by reporter luciferase assays and real-time polymerase chain reaction. We also demonstrate that NR2F2 directly inhibits the activity of the OCT4 promoter and thus diminishes the positive feedback loop between OCT4 and miR-302. Importantly, higher reprogramming efficiencies were obtained when we reprogrammed human adipose-derived stem cells into iPSCs using four factors (KLF4, C-MYC, OCT4, and SOX2) plus miR-302 (this reprogramming cocktail is hereafter referred to as "KMOS3") when compared to using four factors ("KMOS"). Furthermore, shRNA knockdown of NR2F2 mimics the over-expression of miR-302 by also enhancing reprogramming efficiency. Interestingly, we were unable to generate iPSCs from miR-302a/b/c/d alone, which is in contrast to previous publications that have reported that miR-302 by itself can reprogram human skin cancer cells and human hair follicle cells. Taken together, these findings demonstrate that miR-302 inhibits NR2F2 and promotes pluripotency through indirect positive regulation of OCT4. This feedback loop represents an important new mechanism for understanding and inducing pluripotency in somatic cells.
Automatic System Level Test a Fault Location for Large Digital Systems (1978)

A system for automatic test generation and fault location, FLT-700, is described in this paper. It can treat large digital systems with 100K blocks (logic gates) or more. This is realized by utilizing Scan-Path concept, automatic partitioning and test generation techniques and automatic fault location technique. Serviceability for large computer systems can, therefore, be improved and easy maintenance realized.
Specific Inhibition by Cyclodextrins of Raw Starch Digestion by Fungal Glucoamylase (1992)

alpha-, beta-, and gamma-cyclodextrins (CDs) completely inhibited raw starch digestion by glucoamylase I (GA I, MW 90,000) from Aspergillus awamori var. kawachi, and inhibited by 85% the raw starch adsorption of GA I at the CD concentrations of 1-5 mM. CDs at 1-5 mM did not inhibit gelatinized starch hydrolysis by GA I, but at the concentration of 50 mM, they inhibited such hydrolysis slightly. GA I was specifically adsorbed onto CD-Sepharose 6B, but glucoamylase I' (GA I', MW 73,000), which does not adsorb onto or digest raw starch, from the same strain was not adsorbed onto that gel. The adsorption of the glucoamylases onto raw starch and CD-Sepharose 6B was correlated to their digestion of raw starch. The hydrophobic adsorption of GA I onto CDs and raw starch occurred competitively at the Cp region, which is on the C-terminal side of Gp-I in the site for raw starch affinity of GA I, and inclusion complexes were formed.
Expression patterns of Tgfβ1–3 associate with myocardialisation of the outflow tract and the development of the epicardium and the fibrous heart skeleton (2003)

Transforming growth factor-beta (Tgfbeta) is essential for normal embryogenesis. The cardiac phenotypes obtained after knockout of each of the three mammalian isoforms suggest different roles during morphogenesis. We studied cardiovascular expression of Tgfbeta1-3 in parallel tissue sections of normal mouse embryos from 9.5 to 15.5 days post coitum (dpc) by using radioactive in situ hybridisation. The Tgfbeta isoforms are differentially expressed in unique and in overlapping patterns during cardiovascular development. In the vessels, Tgfbeta1 is found in the intima, whereas Tgfbeta2 and -beta3 are mainly present in the media and adventitia of the great arteries. Tgfbeta1 is present in the endocardium at all stages examined. The Tgfbeta2 signal in the endocardium of the atrioventricular canal and outflow tract (9.5 dpc) shifts during epithelial-mesenchymal transformation toward the mesenchymal cushions (10.5-11.5 dpc) after which it exhibits a marked spatiotemporal expression pattern as the cushion differentiation progresses (11.5-15.5 dpc). The myocardium underlying the endocardial cushions and the atrial muscular septum are intensely positive for Tgfbeta2 at early stages (9.5-11.5 dpc) and expression decreases at 12.5 days. In contrast to earlier reports, we find marked overlap of Tgfbeta2 and -beta3 expression. Tgfbeta3 expression shows a characteristic distribution in the mesenchymal cushions, suggesting a role in cushion differentiation, possibly additional to Tgfbeta2. From 14.5 dpc onward, a strong Tgfbeta3 signal is found in the fibrous septum primum of the atrium and in the fibrous skeleton of the heart. Special attention was paid to the proepicardial organ and its derivatives. The proepicardial organ strongly expresses Tgfbeta2 as early as 9.5 days, and all isoforms are present in the epicardium from 12.5 dpc onward. The spatiotemporal cardiovascular expression of Tgfbeta1-3 supports both specific and complementary functions during cardiovascular development that might explain functional redundancy between the Tgfbeta-isoforms. The information provided favors novel roles of Tgfbeta1-3 in epicardial development, of Tgfbeta2 in myocardialisation, and of Tgfbeta3 in differentiation of the fibrous structures of the heart.