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Thiol-Disulphide Balance: Could Be a New Marker for Thyroid Cancer?  [PDF]
Ay?e ?zdemir, ?zcan Erel
Journal of Cancer Therapy (JCT) , 2018, DOI: 10.4236/jct.2018.98051
Abstract: Objectives. Cancer is a very widespread disorder known in world wide since long, but its biochemical features remain unclear. Thyroid carcinomas are the most common endocrine cancer and its frequency continues to escalate. There is evidence that the serum concentration of TSH is an unreliant predictor for the diagnosis of thyroid cancer. The formation of the plasma thiol pool from low and large molecular weight proteins suggests that thiol/disulfide balance is important in cancerous cases. The aim of this study was to investigate an oxidative stress marker (thiol/disulphide homeostasis) and IMA (Ischemia modified albumin), Albumin, CEA (Carcinoembryonic antigen), TSH (Thyroid stimulate hormone), thyroxine (T4), free thyroxine (FT4), triiodothyronine (T3) and free triiodothyronine (FT3) in patients with thyroid cancer and compare the results with healthy controls for the first time in literature. Materials-Methods: A total of 43 participants including 23 patients with thyroid cancer and 20 healthy individuals were included in the study. Serum levels of TSH, T4, FT4, T3 and FT
Benign Proliferative Breast Lesions and Risk of Cancer
Serap Erel
Arsiv Kaynak Tarama Dergisi , 2010,
Abstract: Benign breast lesions (BBL) includes a wide variety of histologic entities, which have been broadly classified into non-proliferative lesions, proliferative lesions without atypia, and hyperplasia with atypia. With the increased use of mammography, more benign lesions are being detected, and in order to estimate the risk of breast cancer for specific histologic categories is of great importance to guide clinical management. Women with proliferative lesions without atypia are at slightly increased risk of subsequent breast cancer, whereas women with proliferative lesions with atypia have a higher risk. The risk is 1.5- 2-fold in women with proliferative lesions without atypia, 4-5-fold in women with proliferative lesions with atypia, and 8-10 fold in women with ductal carcinoma in situ. Age at diagnosis of BBL, menopausal status, family history of breast cancer in a first-degree relative, and time since BBL diagnosis on risk of breast cancer are important for risk evaluation. [Archives Medical Review Journal 2010; 19(3.000): 155-167]
Emergence of a confined state in a weakly bent wire
Erel Granot
Physics , 2001, DOI: 10.1103/PhysRevB.65.233101
Abstract: In this paper we use a simple straightforward technique to investigate the emergence of a bound state in a weakly bent wire. We show that the bend behaves like an infinitely shallow potential well, and in the limit of small bending angle and low energy the bend can be presented by a simple 1D delta function potential.
Estado oxidante/antioxidante total em recém-nascidos ictéricos antes e depois da fototerapia
Aycicek, Ali;Erel, Ozcan;
Jornal de Pediatria , 2007, DOI: 10.1590/S0021-75572007000500006
Abstract: objective: to assess the effect of phototherapy on serum oxidant and antioxidant status in hyperbilirubinemic full-term newborns. method: thirty-four full-term infants from 3 to 10 days of age exposed to phototherapy were studied. the serum antioxidant status was assessed by measuring the total antioxidant capacity (tac) and individual antioxidant components: vitamin c, uric acid, albumin, thiol contents and total bilirubin. the oxidant status was assessed by determining the total oxidant status (tos), oxidative stress index (osi) and individual oxidant components: malondialdehyde (mda), and lipid hydroperoxide levels. results: vitamin c, uric acid, total bilirubin and mda concentration were significantly lower, whereas serum tos, lipid hydroperoxide and osi levels were significantly higher after phototherapy (p < 0.05). there were significant positive correlations between serum total bilirubin and mda (r = 0.434, p = 0.001). conclusions: although the mda level was reduced after phototherapy, phototherapy has a negative impact on numerous parts of the oxidant/antioxidant defense system in jaundiced full-term newborns, exposing them to potential oxidative stress.
Exploring the miRNA Regulatory Network Using Evolutionary Correlations
Benedikt Obermayer ,Erel Levine
PLOS Computational Biology , 2014, DOI: doi/10.1371/journal.pcbi.1003860
Abstract: Post-transcriptional regulation by miRNAs is a widespread and highly conserved phenomenon in metazoans, with several hundreds to thousands of conserved binding sites for each miRNA, and up to two thirds of all genes under miRNA regulation. At the same time, the effect of miRNA regulation on mRNA and protein levels is usually quite modest and associated phenotypes are often weak or subtle. This has given rise to the notion that the highly interconnected miRNA regulatory network exerts its function less through any individual link and more via collective effects that lead to a functional interdependence of network links. We present a Bayesian framework to quantify conservation of miRNA target sites using vertebrate whole-genome alignments. The increased statistical power of our phylogenetic model allows detection of evolutionary correlation in the conservation patterns of site pairs. Such correlations could result from collective functions in the regulatory network. For instance, co-conservation of target site pairs supports a selective benefit of combinatorial regulation by multiple miRNAs. We find that some miRNA families are under pronounced co-targeting constraints, indicating a high connectivity in the regulatory network, while others appear to function in a more isolated way. By analyzing coordinated targeting of different curated gene sets, we observe distinct evolutionary signatures for protein complexes and signaling pathways that could reflect differences in control strategies. Our method is easily scalable to analyze upcoming larger data sets, and readily adaptable to detect high-level selective constraints between other genomic loci. We thus provide a proof-of-principle method to understand regulatory networks from an evolutionary perspective.
Resampling Method For Unsupervised Estimation Of Cluster Validity
Erel Levine,Eytan Domany
Physics , 2000,
Abstract: We introduce a method for validation of results obtained by clustering analysis of data. The method is based on resampling the available data. A figure of merit that measures the stability of clustering solutions against resampling is introduced. Clusters which are stable against resampling give rise to local maxima of this figure of merit. This is presented first for a one-dimensional data set, for which an analytic approximation for the figure of merit is derived and compared with numerical measurements. Next, the applicability of the method is demonstrated for higher dimensional data, including gene microarray expression data.
Braess' Paradox in a Generalised Traffic Network
Vadim Zverovich,Erel Avineri
Computer Science , 2012,
Abstract: The classical network configuration introduced by Braess in 1968 is of fundamental significance because Valiant and Roughgarden showed in 2006 that `the "global" behaviour of an equilibrium flow in a large random network is similar to that in Braess' original four-node example'. In this paper, a natural generalisation of Braess' network is introduced and conditions for the occurrence of Braess' paradox are formulated for the generalised network. The Braess' paradox has been studied mainly in the context of the classical problem introduced by Braess and his colleagues, assuming a certain type of networks. Specifically, two pairs of links in those networks are assumed to have the same volume-delay functions. The occurrence of Braess' paradox for this specific case of network symmetry was investigated by Pas and Principio in 1997. Such a symmetry is not common in real-life networks because the parameters of volume-delay functions are associated with roads physical and functional characteristics, which typically differ from one link to another (e.g. roads in networks are of different length). Our research provides an extension of previous studies on Braess' paradox by considering arbitrary volume-delay functions, i.e. symmetry properties are not assumed for any of the network's links and the occurrence of Braess' paradox is studied for a general configuration.
Inverse Ising inference with correlated samples
Benedikt Obermayer,Erel Levine
Quantitative Biology , 2014, DOI: 10.1088/1367-2630/16/12/123017
Abstract: Correlations between two variables of a high-dimensional system can be indicative of an underlying interaction, but can also result from indirect effects. Inverse Ising inference is a method to distinguish one from the other. Essentially, the parameters of the least constrained statistical model are learned from the observed correlations such that direct interactions can be separated from indirect correlations. Among many other applications, this approach has been helpful for protein structure prediction, because residues which interact in the 3D structure often show correlated substitutions in a multiple sequence alignment. In this context, samples used for inference are not independent but share an evolutionary history on a phylogenetic tree. Here, we discuss the effects of correlations between samples on global inference. Such correlations could arise due to phylogeny but also via other slow dynamical processes. We present a simple analytical model to address the resulting inference biases, and develop an exact method accounting for background correlations in alignment data by combining phylogenetic modeling with an adaptive cluster expansion algorithm. We find that popular reweighting schemes are only marginally effective at removing phylogenetic bias, suggest a rescaling strategy that yields better results, and provide evidence that our conclusions carry over to the frequently used mean-field approach to the inverse Ising problem.
Stochastic fluctuations in metabolic pathways
Erel Levine,Terence Hwa
Quantitative Biology , 2007, DOI: 10.1073/pnas.0610987104
Abstract: Fluctuations in the abundance of molecules in the living cell may affect its growth and well being. For regulatory molecules (e.g., signaling proteins or transcription factors), fluctuations in their expression can affect the levels of downstream targets in a network. Here, we develop an analytic framework to investigate the phenomenon of noise correlation in molecular networks. Specifically, we focus on the metabolic network, which is highly inter-linked, and noise properties may constrain its structure and function. Motivated by the analogy between the dynamics of a linear metabolic pathway and that of the exactly soluable linear queueing network or, alternatively, a mass transfer system, we derive a plethora of results concerning fluctuations in the abundance of intermediate metabolites in various common motifs of the metabolic network. For all but one case examined, we find the steady-state fluctuation in different nodes of the pathways to be effectively uncorrelated. Consequently, fluctuations in enzyme levels only affect local properties and do not propagate elsewhere into metabolic networks, and intermediate metabolites can be freely shared by different reactions. Our approach may be applicable to study metabolic networks with more complex topologies, or protein signaling networks which are governed by similar biochemical reactions. Possible implications for bioinformatic analysis of metabolimic data are discussed.
Small Regulatory RNAs May Sharpen Spatial Expression Patterns
Erel Levine ,Peter McHale ,Herbert Levine
PLOS Computational Biology , 2007, DOI: 10.1371/journal.pcbi.0030233
Abstract: The precise establishment of gene expression patterns is a crucial step in development. Formation of a sharp boundary between high and low spatial expression domains requires a genetic mechanism that exhibits sensitivity, yet is robust to fluctuations, a demand that may not be easily achieved by morphogens alone. Recently, it has been demonstrated that small RNAs (and, in particular, microRNAs) play many roles in embryonic development. Whereas some RNAs are essential for embryogenesis, others are limited to fine-tuning a predetermined gene expression pattern. Here, we explore the possibility that small RNAs participate in sharpening a gene expression profile that was crudely established by a morphogen. To this end, we study a model in which small RNAs interact with a target gene and diffusively move from cell to cell. Though diffusion generally smoothens spatial expression patterns, we find that intercellular mobility of small RNAs is actually critical in sharpening the interface between target expression domains in a robust manner. This sharpening occurs as small RNAs diffuse into regions of low mRNA expression and eliminate target molecules therein, but cannot affect regions of high mRNA levels. We discuss the applicability of our results, as examples, to the case of leaf polarity establishment in maize and Hox patterning in the early Drosophila embryo. Our findings point out the functional significance of some mechanistic properties, such as mobility of small RNAs and the irreversibility of their interactions. These properties are yet to be established directly for most classes of small RNAs. An indirect yet simple experimental test of the proposed mechanism is suggested in some detail.
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