2,257 research outputs found

    Likelihood-based approach to discriminate mixtures of network models that vary in time.

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    Discriminating between competing explanatory models as to which is more likely responsible for the growth of a network is a problem of fundamental importance for network science. The rules governing this growth are attributed to mechanisms such as preferential attachment and triangle closure, with a wealth of explanatory models based on these. These models are deliberately simple, commonly with the network growing according to a constant mechanism for its lifetime, to allow for analytical results. We use a likelihood-based framework on artificial data where the network model changes at a known point in time and demonstrate that we can recover the change point from analysis of the network. We then use real datasets and demonstrate how our framework can show the changing importance of network growth mechanisms over time

    Using a Bayesian approach to reconstruct graph statistics after edge sampling

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    Often, due to prohibitively large size or to limits to data collecting APIs, it is not possible to work with a complete network dataset and sampling is required. A type of sampling which is consistent with Twitter API restrictions is uniform edge sampling. In this paper, we propose a methodology for the recovery of two fundamental network properties from an edge-sampled network: the degree distribution and the triangle count (we estimate the totals for the network and the counts associated with each edge). We use a Bayesian approach and show a range of methods for constructing a prior which does not require assumptions about the original network. Our approach is tested on two synthetic and three real datasets with diverse sizes, degree distributions, degree-degree correlations and triangle count distributions

    Anticholinesterase activity of endemic plant extracts from Soqotra

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    A total of 30 chloroform and methanol extracts from the following endemic Soqotran plants Acridocarpus socotranus Olive, Boswellia socotranao Balf.fil, Boswellia elongata Balf. fil., Caralluma socotrana N. Br, Cephalocroton socotranus Balf.f, Croton socotranus Balf. fil.., Dendrosicycos socotrana Balf.f., Dorstenia gigas Schweinf. ex Balf. fil., Eureiandra balfourii Cogn. & Balf. fil., Kalanchoe farinaceae Balf.f, Limonium sokotranum (Vierh) Radcl. Sm), Oldenlandia pulvinata, Pulicaria diversifolia( Balf. and Pulicaria stephanocarpa Balf. were screened for their acetylcholinesterase inhibitory activity by using in vitro Ellman method at 50 and 200 μg/ml concentrations. Chloroform extracts of Croton socotranus, Boswellia socotrana, Dorstenia gigas, and Pulicaria stephanocarpa as well as methanol extracts of Eureiandra balfourii exhibited inhibitory activities higher than 50 % at concentration of 200 μg. At a concentrations of 50 μg, the chloroform extract of Croton socotranus exhibited an inhibition of 40.6 %.Key words: plant extracts, acetylcholinesterase inhibitors, Soqotra, Alzheimer’s diseas

    Poly[3,3′-diethyl-1,1′-(ethane-1,2-di­yl)diimidazolium [tetra-μ-bromido-­diargentate(I)]]

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    The asymmetric unit of the title salt, {(C12H20N4)[Ag2Br4]}n, contains one-half of a substituted imidazolium cation, one Ag+ and two Br− ions. The cation is completed by crystallographic inversion symmetry. The crystal structure is made up from polymeric sheets of {[AgBr2]−}n anions extending parallel to (100). The basic building unit of the anion is a slightly distorted AgBr4 tetra­hedron. A four- and 12-membered ring system is formed by corner sharing of the AgBr4 tetra­hedra. The imidazolium cations are located between the anionic sheets and partly protrude into the voids defined by the 12-membered rings

    Impact of early remission by induction therapy on allogeneic stem cell transplantation for acute myeloid leukemia with an intermediate risk karyotype in first complete remission

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    For patients with acute myeloid leukemia (AML) early achievement of remission during induction treatment is an important predictor for long-term outcome irrespective of the type of consolidation therapy employed. Here, we retrospectively examined the prognostic impact of early remission (ER) versus delayed remission (DR) in a cohort of 132 AML patients with an intermediate risk karyotype undergoing allogeneic stem cell transplantation (alloSCT) in first complete remission (CR1). In contrast to patients showing DR, patients achieving ER had a significantly higher 3-year overall survival (OS) and disease-free survival (DFS) of 76% versus 54% (p=0.03) and 76% versus 53% (p=0.03). Likewise, three years after alloSCT the cumulative incidence of relapse (CI-R) was significantly lower in the ER subgroup as compared to patients achieving DR, i.e. 10% versus 35% (p=0.004), whereas non-relapse mortality (NRM) did not differ significantly. Multivariate analysis identified DR as an independent prognosticator for an inferior DFS (HR 3.37, p=0.002) and a higher CI-R (HR 3.55, p=0.002). Taken together, these data may indicate that the rapid achievement of remission predicts a favorable outcome in patients with intermediate risk AML undergoing alloSCT in CR1. In turn, the adverse effect of DR may not be fully overcome by alloSCT

    The Expression of MicroRNA miR-107 Decreases Early in Alzheimer\u27s Disease and May Accelerate Disease Progression through Regulation of β-Site Amyloid Precursor Protein-Cleaving Enzyme 1

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    MicroRNAs (miRNAs) are small regulatory RNAs that participate in posttranscriptional gene regulation in a sequence-specific manner. However, little is understood about the role(s) of miRNAs in Alzheimer\u27s disease (AD). We used miRNA expression microarrays on RNA extracted from human brain tissue from the University of Kentucky Alzheimer\u27s Disease Center Brain Bank with near-optimal clinicopathological correlation. Cases were separated into four groups: elderly nondemented with negligible AD-type pathology, nondemented with incipient AD pathology, mild cognitive impairment (MCI) with moderate AD pathology, and AD. Among the AD-related miRNA expression changes, miR-107 was exceptional because miR-107 levels decreased significantly even in patients with the earliest stages of pathology. In situ hybridization with cross-comparison to neuropathology demonstrated that particular cerebral cortical laminas involved by AD pathology exhibit diminished neuronal miR-107 expression. Computational analysis predicted that the 3′-untranslated region (UTR) of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) mRNA is targeted multiply by miR-107. From the same RNA material analyzed on miRNA microarrays, mRNA expression profiling was performed using Affymetrix Exon Array microarrays on nondemented, MCI, and AD patients. BACE1 mRNA levels tended to increase as miR-107 levels decreased in the progression of AD. Cell culture reporter assays performed with a subset of the predicted miR-107 binding sites indicate the presence of at least one physiological miR-107 miRNA recognition sequence in the 3′-UTR of BACE1 mRNA. Together, the coordinated application of miRNA profiling, Affymetrix microarrays, new bioinformatics predictions, in situ hybridization, and biochemical validation indicate that miR-107 may be involved in accelerated disease progression through regulation of BACE1

    Focus on RNA Isolation: Obtaining RNA for MicroRNA (miRNA) Expression Profiling Analyses of Neural Tissue

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    MicroRNAs (miRNAs) are present in all known plant and animal tissues and appear to be somewhat concentrated in the mammalian nervous system. Many different miRNA expression profiling platforms have been described. However, relatively little research has been published to establish the importance of \u27upstream\u27 variables in RNA isolation for neural miRNA expression profiling. We tested whether apparent changes in miRNA expression profiles may be associated with tissue processing, RNA isolation techniques, or different cell types in the sample. RNA isolation was performed on a single brain sample using eight different RNA isolation methods, and results were correlated using a conventional miRNA microarray and then cross-referenced to Northern blots. Differing results were seen between samples obtained using different RNA isolation techniques and between microarray and Northern blot results. Another complication of miRNA microarrays is tissue-level heterogeneity of cellular composition. To investigate this phenomenon, miRNA expression profiles were determined and compared between highly-purified primary cerebral cortical cell preparations of rat primary E15-E18 neurons versus rat primary E15-E18 astrocytes. Finally, to assess the importance of dissecting human brain gray matter from subjacent white matter in cerebral cortical studies, miRNA expression profiles were compared between gray matter and immediately contiguous white matter. The results suggest that for microarray studies, cellular composition is important, and dissecting white matter from gray matter improves the specificity of the results. Based on these data, recommendations for miRNA expression profiling in neural tissues, and considerations worthy of further study, are discussed

    Sentinel node in ovarian cancer : study protocol for a phase 1 study

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    Background: The concept of sentinel lymph node surgery is to determine whether the cancer has spread to the very first lymph node or sentinel node. If the sentinel node does not contain cancer, then there is a high likelihood that the cancer has not spread to other lymph nodes. The sentinel node technique has been proven to be effective in different types of cancer. In this study we want to determine whether a sentinel node procedure in patients with ovarian cancer is feasible when the tracers are injected into the ovarian ligaments. Methods/Design: Patients with a high likelihood of having an ovarian malignancy in whom a median laparotomy and a frozen section analysis is planned and patients with endometrial cancer in whom a staging laparotomy is planned will be included. Before starting the surgical staging procedure, blue dye and radioactive colloid will be injected into the ligamentum ovarii proprium and the ligamentum infundibulo-pelvicum. In the analysis we calculate the percentage of patients in whom it is feasible to identify sentinel nodes. Other study parameters are the anatomical localization of the sentinel node(s) and the incidence of false negative lymph nodes

    Utilization of TREC and KREC quantification for the monitoring of early T- and B-cell neogenesis in adult patients after allogeneic hematopoietic stem cell transplantation

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    BACKGROUND: After hematopoietic stem cell transplantation (HSCT) T- and B-cell reconstitution from primary lymphoid organs are a prerequisite for an effective early lymphocyte reconstitution and a long-term survival for adult patients suffering from acute leukemia. Here, we asked whether quantification of T cell receptor excision circle, (TREC) and kappa-deleting recombination excision circle (KREC) before and within six month after allogeneic HSCT could be used to measure the thymic and bone marrow outputs in such patients. METHODS: We used a duplex real time PCR assay to quantify the absolute copy counts of TREC and KREC, and correlated the data with absolute cell counts of CD3+CD4+ T-cell and CD19+ B-cell subsets determined by flow cytometry, respectively. RESULTS: By comparing two recently proposed naive T cell subsets, CD31+ naive and CD31- naive T cells, we found a better correlation for the CD31+ subset with TREC level post alloHSCT, in line with the assumption that it contained T cells recently derived from the thymus, indicating that TREC levels reflected real thymic de novo production. Transitional as well as naive B cells highly correlated with KREC levels, which suggested an association of KREC levels with ongoing bone marrow B cell output. CD45RO+ memory T cells and CD27+ memory B cells were significantly less correlated with TREC and KREC recovery, respectively. CONCLUSION: We conclude that simultaneous TREC/ KREC quantification is as a suitable and practicable method to monitor thymic and bone marrow output post alloHSCT in adult patients diagnosed with acute leukemia
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