gebhart/patrepeval huggingface dataset:
LEARNING BAYESIAN BELIEF NETWORKS: AN APPROACH BASED ON THE MDL PRINCIPLE (1994)

A new approach for learning Bayesian belief networks from raw data is presented. The approach is based on Rissanen's minimal description length (MDL) principle, which is particularly well suited for this task. Our approach does not require any prior assumptions about the distribution being learned. In particular, our method can learn unrestricted multiply‐connected belief networks. Furthermore, unlike other approaches our method allows us to trade off accuracy and complexity in the learned model. This is important since if the learned model is very complex (highly connected) it can be conceptually and computationally intractable. In such a case it would be preferable to use a simpler model even if it is less accurate. The MDL principle offers a reasoned method for making this trade‐off. We also show that our method generalizes previous approaches based on Kullback cross‐entropy. Experiments have been conducted to demonstrate the feasibility of the approach.
Diesel Fuel from Vegetable Oil via Transesterification and Soap Pyrolysis (2002)

Abstract Transesterifications of 6 vegetable oil samples in supercritical methanol (SC MeOH) were studied without using any catalyst. Methyl esters of vegetable oils have several outstanding advantages among other new-renewable and clean engine fuel alternatives. The variables affecting the methyl ester yielded during the transesterification reaction, such as the molar ratio of alcohol to vegetable oil and reaction temperature, were investigated. Compared to No. 2 diesel fuel, all of the vegetable oils are much more viscous, while methyl esters of vegetable oils are the slightly more viscous. The methyl esters are more volatile than those of the vegetable oils. The soaps obtained from the vegetable oils can be pyrolyzed into hydrocarbon-rich products. Keywords: Vegetable Oil Transesterification Methyl Ester Soap Pyrolysis
The synthesis of malonimide derivatives as potential penicillin analogs (1972)

Abstract Malonimidoacetic acid derivatives (VIII, XIII) were synthesized as a potential penicillin analogs, hut they failed to inhibit the growth of bacteria when tested in vitro against a range of Gram‐positive and Gram‐negative microorganisms.
Pharmacological characterization of endothelin‐induced rat pulmonary arterial dilatation (1997)

1. The aim of study was to characterize endothelin (ET)-induced vasodilation in isolated extrapulmonary rat arteries (EPA) and in intrapulmonary arteries (IPA) preconstricted with 1 microM phenylephrine. 2. The ET-3 (1 nM-100 nM)- and ET-1 (10 nM-100 nM)-induced transient vasodilatations in EPA were more potent than those in IPA. The vasodilatation induced by ET-3 (100 nM) was larger than that induced by ET-1 (100 nM). 3. Both the ETB antagonist, BQ788 (3 microM) and or endothelium denudation, but not the ETA antagonist, BQ123 (3 microM), abolished the vasodilation induced by ET-1 or ET-3 (100 nM each) in EPA and in IPA. The ATP-sensitive K + channel blocker, glibenclamide (20 microM) and the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA, 1 mM) suppressed the ET-induced vasodilatation in EPA and in IPA. 4. We conclude that the vasodilatation induced by endothelins is markedly reduced in rat isolated IPA, and suggest that the endothelial ETB-mediated vasodilatation varies depending on rat pulmonary arterial regions. Furthermore, ETB-mediated vasodilatation involves activation of ATP-sensitive K+ channels and of nitric oxide synthase in rat isolated EPA and IPA.
Bioactive β-Carbolines in Food: A Review (2019)

Harman and norharman, two neuroactive β-carbolines, are present in several plants and in thermally processed foods. They exhibited a wide spectrum of biological and pharmacological effects, including antioxidant, neuroprotective, and anti-inflammatory effects. In this article, we review the progress of recent research on the presence of these compounds in food, as well as their various biological and neuroactive properties. Our findings strongly suggest that some foods, especially coffee, can act as a rich source of β-carbolines, which may possibly be associated with a reduced risk for serious neurodegenerative diseases, such as Parkinson's and Alzheimer's.
cDNA Cloning and Chromosomal Localization of Human α11 Integrin (1999)

We previously identified a novel integrin alpha-chain in human fetal muscle cells (Gullberg, D., Velling, T., Sjöberg, G., and Sejersen, T. (1995) Dev. Dyn. 204, 57-65). We have now isolated the full-length cDNA for this integrin subunit, alpha(11). The open reading frame of the cDNA encodes a precursor of 1188 amino acids. The predicted mature protein of 1166 amino acids contains seven conserved FG-GAP repeats, an I domain with a metal ion-dependent adhesion site motif, a short transmembrane region, and a unique cytoplasmic domain of 24 amino acids containing the sequence GFFRS. alpha(11), like other I domain integrins, lacks a dibasic cleavage site for generation of a heavy chain and a light chain, and it contains three potential divalent cation binding sites in repeats 5-7. The presence of 22 inserted amino acids in the extracellular stalk portion (amino acids 804-826) distinguishes the alpha(11) integrin sequence from other integrin alpha-chains. Amino acid sequence comparisons reveal the highest identity of 42% with the alpha(10) integrin chain. Immunoprecipitation with antibodies to alpha(11) integrin captures a 145-kDa protein distinctly larger than the 140-kDa alpha(2) integrin chain when analyzed by SDS-polyacrylamide gel electrophoresis under nonreducing conditions. Fluorescence in situ hybridization maps the integrin alpha(11) gene to chromosome 15q23, in the vicinity of an identified locus for Bardet-Biedl syndrome. Based on Northern blotting, integrin alpha(11) mRNA levels are high in the adult human uterus and in the heart and intermediate in skeletal muscle and some other tissues tested. During in vitro myogenic differentiation, alpha(11) mRNA and protein are up-regulated. Studies of ligand binding properties show that alpha(11)beta(1) binds collagen type I-Sepharose, and cultured muscle cells localize alpha(11)beta(1) into focal contacts on collagen type I. Future studies will reveal the importance of alpha(11)beta(1) for muscle development and integrity in adult muscle and other tissues.
Anthocyanin Biosynthesis in Flowers of Matthiola incana Flavanone 3-and Flavonoid 3′-Hydroxylases (1980)

Abstract Enzyme preparations from flowers of defined genotypes of Matthiola incana contain two dif­ ferent hydroxylases for hydroxylation of naringenin in the 3-and 3′-position, respectively. The 3-hydroxylase is a soluble enzyme and requires as cofactors 2-oxoglutarate, Fe 2+ and ascorbate. Besides naringenin eriodictyol is a substrate for the 3-hydroxylase. The 3′-hydroxylase is localized in the microsomal fraction and requires NADPH as cofactor. Naringenin and dihydro-kaempferol but not 4-coumarate or 4-coumaroyl-CoA are substrates for this enzyme. 3′-Hydroxylase activity is present only in genetic lines of M. incana with the wild-type allele b + .
Glypican‐3 protein expression in primary and metastatic melanoma (2009)

In the current study, all MM and PM cases in archival FNAs and tissue sections were found to be negative for GPC3. These data suggest that GPC3 is not expressed in melanoma using the 1G12 clone.
Targeted Delivery of siRNA‐Generating DNA Nanocassettes Using Multifunctional Nanoparticles (2013)

Molecular therapy using a small interfering RNA (siRNA) has shown promise in the development of novel therapeutics. Various formulations have been used for in vivo delivery of siRNAs. However, the stability of short double-stranded RNA molecules in the blood and efficiency of siRNA delivery into target organs or tissues following systemic administration have been the major issues that limit applications of siRNA in human patients. In this study, multifunctional siRNA delivery nanoparticles are developed that combine imaging capability of nanoparticles with urokinase plasminogen activator receptor-targeted delivery of siRNA expressing DNA nanocassettes. This theranostic nanoparticle platform consists of a nanoparticle conjugated with targeting ligands and double-stranded DNA nanocassettes containing a U6 promoter and a shRNA gene for in vivo siRNA expression. Targeted delivery and gene silencing efficiency of firefly luciferase siRNA nanogenerators are demonstrated in tumor cells and in animal tumor models. Delivery of survivin siRNA expressing nanocassettes into tumor cells induces apoptotic cell death and sensitizes cells to chemotherapy drugs. The ability of expression of siRNAs from multiple nanocassettes conjugated to a single nanoparticle following receptor-mediated internalization should enhance the therapeutic effect of the siRNA-mediated cancer therapy.
DNA Branched Junctions (1994)

Many bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) systems employ the dual RNA–guided DNA endonuclease Cas9 to defend against invading phages and conjugative plasmids by introducing site-specific ...Read More
DIALLELIC POLYMORPHISM MAY EXPLAIN VARIATIONS OF THE BLOOD CONCENTRATION OF MANNAN‐BINDING PROTEIN IN ESKIMOS, BUT NOT IN BLACK AFRICANS (1992)

Mannan-binding protein (MBP) is a lectin which, upon binding to certain carbohydrates, activates the classical pathway of complement without the involvement of antibody or C1q. Deficiency of the MBP is associated with an opsonic defect and recurrent infections during early life. An amino acid substitution in the exon 1 at codon 54 in the MBP gene (GGC [glycine] to GAC [aspartic acid]) has been shown to be closely associated with low MBP concentration in Caucasoids. The gene frequency of the mutant allele in this population has been estimated at 0.13. In the study described here, we investigated the association between the mutant allele and MBP protein concentration in Eskimos from East-Greenland and black Africans from the Baringo District in Kenya. The frequency of the GAC allele was identical in Eskimos and Caucasoids (0.13). No overlap with regard to MBP concentration between the genotypes was found in the Eskimos. In contrast, the Africans revealed a low frequency of the GAC allele (0.009). However, the median MBP protein concentration was approximately 5 times lower among the Africans than the Eskimos. In 12.6% of the Africans and in 2.5% of the Eskimos, MBP was undetectable. Thus, MBP deficiency is the most frequent immunodeficiency so far described. The high prevalence of MBP deficiency among healthy individuals indicates that MBP deficiency also confers some selective advantages. We advance the hypothesis that MBP deficiency is maintained in populations because MBP deficiency decreases the infectivity of some intracellular micro-organisms which are dependent on opsonization.
Spatially confined nickel disilicide formation at 400 °C on ion implantation preamorphized silicon (1993)

The localized formation of continuous silicide layers via solid state reaction of nickel atoms with ion implantation preamorphized silicon is described. Ni films 12 nm thick were evaporated on 65 nm deep amorphized surface layers. The silicidation reaction was induced by two stage thermal annealing at 360 and 400 °C, well below the solid phase epitaxial regrowth temperature for amorphous Si and the normal NiSi2 formation temperature. Rutherford backscattering with channeling, XTEM, and four-point-probe measurements were used to determine the structure, interfacial morphology, composition, and resistivity of the silicide films. After the lower temperature annealing stage a continuous layer of NiSi2 is formed with an underlying residual amorphous region located above the crystalline substrate. During a second annealing the residual amorphous areas recrystallize epitaxially with respect to the substrate via lateral silicide growth. The process leads to formation of a continuous 35 nm thick nickel disilicide layer completely confined within the original amorphous region. Silicide resistivity was 44 μΩ cm. The process may be viewed as a low-temperature process enhancement to self-aligned silicide (SALICIDE) technology since silicide growth proceeds only on preamorphized areas of the silicon substrate.
Rab7b controls trafficking from endosomes to the TGN (2010)

Rab7b is a recently identified member of the Rab GTPase protein family and has high similarity to Rab7. It has been reported that Rab7b is lysosome associated, that it is involved in monocytic differentiation and that it promotes lysosomal degradation of TLR4 and TLR9. Here we investigated further the localization and function of this GTPase. We found that wild-type Rab7b is lysosome associated whereas an activated, GTP-bound form of Rab7b localizes to the Golgi apparatus. In contrast to Rab7, Rab7b is not involved in EGF and EGFR degradation. Depletion of Rab7b or expression of Rab7b T22N, a Rab7b dominant-negative mutant, impairs cathepsin-D maturation and causes increased secretion of hexosaminidase. Moreover, expression of Rab7b T22N or depletion of Rab7b alters TGN46 distribution, cation-independent mannose-6-phosphate receptor (CI-MPR) trafficking, and causes an increase in the levels of the late endosomal markers CI-MPR and cathepsin D. Vesicular stomatitis virus G protein (VSV-G) trafficking, by contrast, is normal in Rab7b-depleted or Rab7b-T22N-expressing cells. In addition, depletion of Rab7b prevents cholera toxin B-subunit from reaching the Golgi. Altogether, these data indicate that Rab7b is required for normal lysosome function, and, in particular, that it is an essential factor for retrograde transport from endosomes to the trans-Golgi network (TGN).
Structural and photophysical properties of luminescent cyanometallates [M(diimine)(CN)4]2− and their supramolecular assemblies (2010)

Luminescent complexes of the [M(diimine)(CN)(4)](2-) family (M = Ru, Os), and their polynuclear analogues, are structurally versatile components for preparation of supramolecular assemblies based on interaction of the cyanide groups with other metal ions or metal complexes via direct coordination, hydrogen bonding, or halogen bonding. In addition their environment-dependent photophysical properties (solvatochromism and metallochromism), and the ability of the CN groups to act as reporters for excited state behaviour via time-resolved IR spectroscopy, make these fragments spectroscopically as well as structurally versatile. This Perspective article summarises work from the author's group over the last decade on the structures and photophysical properties of these fascinating complexes and their supramolecular assemblies.
Microglia and prion disease: a review. (1997)

Prion diseases are characterized by the accumulation of PrPSc, an altered isoform of a normal cellular protein, PrPc. The prion hypothesis holds that the process of conformational change from PrPc to PrPSc under the influence of PrPSc constitutes the basic infectious mechanism in prion diseases. It is still unknown whether pathological changes in these diseases, which include spongiform degeneration, nerve cell loss and gliosis, are the result of neurotoxicity of PrPSc, loss of function of PrPc or some other mechanism. Recent in vitro findings using a synthetic peptide of human PrPc implicate microglia as a mediator of pathological changes. The mechanism of the toxicity of this peptide involves activation of microglia oxidative stress, and direct interactions with PrPc-synthesizing neurones that reduce their ability to cope with oxidative stress. Microglia thus seem to emerge as a mediator of neuronal degeneration and cell death in prion diseases.
Mir-144 selectively regulates embryonic α-hemoglobin synthesis during primitive erythropoiesis (2008)

Precise transcriptional control of developmental stage-specific expression and switching of alpha- and beta-globin genes is significantly important to understand the general principles controlling gene expression and the pathogenesis of thalassemia. Although transcription factors regulating beta-globin genes have been identified, little is known about the microRNAs and trans-acting mechanism controlling alpha-globin genes transcription. Here, we show that an erythroid lineage-specific microRNA gene, miR-144, expressed at specific developmental stages during zebrafish embryogenesis, negatively regulates the embryonic alpha-globin, but not embryonic beta-globin, gene expression, through physiologically targeting klfd, an erythroid-specific Krüppel-like transcription factor. Klfd selectively binds to the CACCC boxes in the promoters of both alpha-globin and miR-144 genes to activate their transcriptions, thus forming a negative feedback circuitry to fine-tune the expression of embryonic alpha-globin gene. The selective effect of the miR-144-Klfd pathway on globin gene regulation may thereby constitute a novel therapeutic target for improving the clinical outcome of patients with thalassemia.
Suppression of hepcidin during anemia requires erythropoietic activity (2006)

Hepcidin, the principal iron regulatory hormone, regulates the absorption of iron from the diet and the mobilization of iron from stores. Previous studies indicated that hepcidin is suppressed during anemia, a response that would appropriately increase the absorption of iron and its release from stores. Indeed, in the mouse model, hepcidin-1 was suppressed after phlebotomy or erythropoietin administration but the suppression was reversed by inhibitors of erythropoiesis. The suppression of hepcidin necessary to match iron supply to erythropoietic demand thus requires increased erythropoiesis and is not directly mediated by anemia, tissue hypoxia, or erythropoietin.
Complement Deficiency Ameliorates Collagen-Induced Arthritis in Mice (2002)

Collagen-induced arthritis (CIA) is an experimental animal model of human rheumatoid arthritis being characterized by synovitis and progressive destruction of cartilage and bone. CIA is induced by injection of heterologous or homologous collagen type II in a susceptible murine strain. DBA/1J mice deficient of complement factors C3 (C3(-/-)) and factor B (FB(-/-)) were generated to elucidate the role of the complement system in CIA. When immunized with bovine collagen type II emulsified in CFA, control mice developed severe arthritis and high CII-specific IgG Ab titers. In contrast, the C3(-/-) and FB(-/-) were highly resistant to CIA and displayed decreased CII-specific IgG Ab response. A repeated bovine collagen type II exposure 3 wk after the initial immunization led to an increase in the Ab response in all mice and triggered arthritis also in the complement-deficient mice. Although the arthritic score of the C3(-/-) mice was low, the arthritis in FB(-/-) mice ranked intermediate with regard to C3(-/-) and control mice. We conclude that complement activation by both the classical and the alternative pathway plays a deleterious role in CIA.
Bioinspired Syntheses of Partially Methylated Flavonoids – Untapped Source of Bioactivities (2017)

Alkylation of hydroxyl groups of flavonoids is known to increase their bioavailability, metabolic stability and also impart new bioactivities. Though partially alkylated flavonoids and related compounds occupy substantial chemical space, there is scant information on their biological activities. They are comparatively less accessible, therefore development of their general syntheses are desirable. Chalcones play key role in the biosynthesis of array of flavonoids. Taking cues from nature, bioinspired, ecofriendly syntheses of polyhydroxy- and partially alkylated flavonoids have been developed. Compared to conventional protection groups, methoxymethylation was found to be more useful for the protection of hydroxyl groups. A library of flavones, flavonols, isoflavones and biflavones has been prepared. A brief account of our ongoing effort towards syntheses of small molecules is summarized here. Biological screening of the synthesized compounds led to recognition of several hitherto unreported inhibitors of biomarkers for MMP’s, NFkB, carbonic anhydrase etc.
Dominant Role for TL1A/DR3 Pathway in IL-12 plus IL-18-Induced IFN-γ Production by Peripheral Blood and Mucosal CCR9+ T Lymphocytes (2005)

The TNF-like cytokine TL1A augments IFN-gamma production by anti-CD3 plus anti-CD28 and IL-12/IL-18-stimulated peripheral blood (PB) T cells. However, only a small subset of PB T cells respond to TL1A stimulation with IFN-gamma production. PB CCR9+ T cells represent a small subset of circulating T cells with mucosal T cell characteristics and a Th1/Tr1 cytokine profile. In the current study, we show that TL1A enhanced IFN-gamma production by TCR- or CD2/CD28-stimulated CCR9(+)CD4+ PB T cells. However, TL1A had the most pronounced effect on augmenting IFN-gamma production by IL-12/IL-18-primed CCR9(+)CD4+ PB T cells. TL1A enhanced both the percentage and the mean fluorescence intensity of IFN-gamma in CCR9(+)CD4+ T cells as assessed by intracellular cytokine staining. IL-12 plus IL-18 up-regulated DR3 expression in CCR9(+)CD4+ T cells but had negligible effect on CCR9(-)CD4+ T cells. CCR9(+)CD4+ T cells isolated from the small intestine showed a 37- to 105-fold enhancement of IFN-gamma production when TL1A was added to the IL-12/IL18 cytokine combination. Cell membrane-expressed TL1A was preferentially expressed in CCR9(+)CD4+ PB T cells, and a blocking anti-TL1A mAb inhibited IFN-gamma production by cytokine-primed CCR9(+)CD4+ T cells by approximately 50%. Our data show that the TL1A/DR3 pathway plays a dominant role in the ultimate level of cytokine-induced IFN-gamma production by CCR9+ mucosal and gut-homing PB T cells and could play an important role in Th1-mediated intestinal diseases, such as Crohn's disease, where increased expression of IL-12, IL-18, TL1A, and DR3 converge in the inflamed intestinal mucosa.
Dominant negative mutations in the Tn10 tet repressor: evidence for use of the conserved helix-turn-helix motif in DNA binding. (1985)

The Tn10 tet repressor regulates transcription of the tetracycline-resistance determinant in transposon Tn10. Previous DNA sequencing studies identified a region of tet repressor (amino acids 26-47) that is homologous to the helix-turn-helix regions of lambda Cro, lambda repressor, and catabolite gene activator protein that are implicated in sequence-specific DNA binding. Here we report the isolation of dominant tetR mutations that result in tet repressors deficient in tet operator binding but that retain some capacity to form dimers with, and thereby inactivate, wild-type repressor monomers. The mutations were isolated by transforming a tetR+ tetA-lacZ fusion strain with hydroxylamine-mutagenized tetR plasmid DNA and then screening for increased lacZ expression. DNA sequence analysis of 35 independent isolates identified seven different mutations, five of which are in the region of helix-turn-helix sequence homology. In vitro binding studies indicate that the mutations in this region of tet repressor reduce the affinity of tet repressor for tet operator DNA by at least a factor of 1000 but have no significant effect on the affinity of tet repressor for tetracycline. These results provide strong support for the proposal that tet repressor utilizes the conserved helix-turn-helix structural motif in binding to tet operator DNA.