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- Alghamdi, Azza
(författare)
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Approximation of pluricomplex Green functions : A probabilistic approach
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This PhD thesis focuses on probabilistic methods of approximation of pluricomplex Green functions and is based on four papers.The thesis begins with a general introduction to the use of pluricomplex Green functions in multidimensional complex analysis and a review of their main properties. This is followed by short description of the main results obtained in the enclosed papers.In Paper I, we study properties of the metric space of pluriregular sets, that is zero sets of continuous pluricomplex Green functions. The best understood non-trivial examples of such sets are composite Julia sets, obtained by iteration of finite families of polynomial mappings in several complex variables. We prove that the so-called chaos game is applicable in the case of such sets. We also visualize some composite Julia sets using escape time functions and Monte Carlo simulation.In Paper II, we extend results in Paper I to the case of infinite compact families of proper polynomials mappings. With composition as the semigroup operation, we generate families of infinite iterated function systems with compact attractors. We show that such attractors can be approximated probabilistically in a manner of the classic chaos game.In Paper III, we study numerical approximation and visualisation of pluricomplex Green functions based on the Monte-Carlo integration. Unlike alternative methods that rely on locating a sequence of carefully chosen finite sets of points satisfying some optimal conditions for approximation purposes, our approach is simpler and more direct by relying on generation of pseudorandom points. We examine numerically the errors of approximation for some simple geometric shapes for which the pluricomplex Green functions are known. If the pluricomplex Green functions are not known, the errors in Monte Carlo integration can be expressed with the aid of statistics in terms of confidence intervals.Finally, in Paper IV, we study how perturbations of an orthonomalization procedure influence the resulting approximate Bergman functions. To this end we consider the concept of near orthonormality of a finite set of vectors in an inner product space, understood as closeness of the Gram matrix of those vectors to the identity matrix. We provide estimates for the errors resulting from using nearly orthogonal bases instead of orthogonal ones. The motivation for this work comes from Paper III: when Gram matrices are calculated via Monte Carlo integration, the outcomes of standard orthogonalisation algorithms are nearly orthonormal bases.
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- Alghamdi, Azza, et al.
(författare)
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Attractors of compactly generated semigroups of regular polynomial mappings.
- 2018
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Ingår i: Complexity. - : Hindawi Limited. - 1076-2787 .- 1099-0526.
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the metric space of pluriregular sets as well as the contractions on that space induced by infinite compact families of proper polynomial mappings of several complex variables. The topological semigroups generated by such families, with composition as the semigroup operation, lead to the constructions of a variety of Julia-type pluriregular sets. The generating families can also be viewed as infinite iterated function systems with compact attractors. We show that such attractors can be approximated both deterministically and probabilistically in a manner of the classic chaos game.
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- Alghamdi, Azza, et al.
(författare)
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Probabilistic approximation of partly filled-in composite Julia sets
- 2017
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Ingår i: Annales Polonici Mathematici. - : Institute of Mathematics, Polish Academy of Sciences. - 0066-2216 .- 1730-6272. ; 119:3, s. 203-220
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Tidskriftsartikel (refereegranskat)abstract
- We study properties of the metric space of pluriregular sets and of contractions on that space induced by finite families of proper polynomial mappings of several complex variables. In particular, we show that closed balls in the space of pluriregular sets do not have to be compact and we give a simple proof of applicability of the so-called chaos game in the case of composite Julia sets. Part of the construction of those sets also leads to a computationally viable approximation by simpler sets based on Monte-Carlo simulation.
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- Chapman, Lesley M, et al.
(författare)
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A crowdsourced set of curated structural variants for the human genome
- 2020
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Ingår i: PLoS Computational Biology. - : Public Library of Science (PLoS). - 1553-7358. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- A high quality benchmark for small variants encompassing 88 to 90% of the reference genome has been developed for seven Genome in a Bottle (GIAB) reference samples. However a reliable benchmark for large indels and structural variants (SVs) is more challenging. In this study, we manually curated 1235 SVs, which can ultimately be used to evaluate SV callers or train machine learning models. We developed a crowdsourcing app - SVCurator - to help GIAB curators manually review large indels and SVs within the human genome, and report their genotype and size accuracy. SVCurator displays images from short, long, and linked read sequencing data from the GIAB Ashkenazi Jewish Trio son [NIST RM 8391/HG002]. We asked curators to assign labels describing SV type (deletion or insertion), size accuracy, and genotype for 1235 putative insertions and deletions sampled from different size bins between 20 and 892,149 bp. 'Expert' curators were 93% concordant with each other, and 37 of the 61 curators had at least 78% concordance with a set of 'expert' curators. The curators were least concordant for complex SVs and SVs that had inaccurate breakpoints or size predictions. After filtering events with low concordance among curators, we produced high confidence labels for 935 events. The SVCurator crowdsourced labels were 94.5% concordant with the heuristic-based draft benchmark SV callset from GIAB. We found that curators can successfully evaluate putative SVs when given evidence from multiple sequencing technologies.
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| 8. |
- Chapman, Lesley M, et al.
(författare)
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SVCurator: A Crowdsourcing app to visualize evidence of structural variants for the human genome
- 2019
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- A high quality benchmark for small variants encompassing 88 to 90% of the reference genome has been developed for seven Genome in a Bottle (GIAB) reference samples. However a reliable benchmark for large indels and structural variants (SVs) is yet to be defined. In this study, we manually curated 1235 SVs which can ultimately be used to evaluate SV callers ortrain machine learning models. We developed a crowdsourcing app - SVCurator - to help curators manually review large indels and SVs within the human genome, and report their genotype and size accuracy.SVCurator is a Python Flask-based web platform that displays images from short, long, and linked read sequencing data from the GIAB Ashkenazi Jewish Trio son [NIST RM 8391/HG002]. We asked curators to assign labels describing SV type (deletion or insertion), size accuracy, and genotype for 1235 putative insertions and deletions sampled from different size bins between 20 and 892,149 bp. The crowdsourced results were highly concordant with 37 out ofthe 61 curators having at least 78% concordance with a set of ‘expert’ curators, where there was 93% concordance amongst ‘expert’ curators. This produced high confidence labels for 935 events. When compared to the heuristic-based draft benchmark SV callset from GIAB, the SVCurator crowdsourced labels were 94.5% concordant with the benchmark set. We found that curators can successfully evaluate putative SVs when given evidence from multiple sequencing technologies.
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- El-Garawani, Islam, et al.
(författare)
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The Ameliorative Role of Acacia senegal Gum against the Oxidative Stress and Genotoxicity Induced by the Radiographic Contrast Medium (Ioxitalamate) in Albino Rats
- 2021
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Ingår i: Antioxidants. - : MDPI AG. - 2076-3921. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Arabic gum (Acacia senegal, AG) is proven effective antioxidant and cytoprotective agent. The present study was designed to test this notion by investigating the possible role of AG against the radiographic contrast medium (Ioxitalamate, Telebrix-35®, TBX)-induced oxidative stress and genotoxicity. Albino rats were divided into four groups and supplied with either; distilled water, daily 10% (w/v) AG, an intravenous dose of TBX (1600 mg I/kg b.wt) and co-administration of TBX and AG. Rats were sacrificed and blood samples were collected to assess the genotoxicity employing the peripheral blood leucocytes fluorescent double staining; namely the acridine orange/ethidium bromide (AO/EB) staining and alkaline comet assay. Further, chromosomal analyses were done in bone marrow cells. Serum urea and creatinine levels, in addition to malondialdehyde (MDA), nitric oxide (NO), catalase (CAT) and glutathione (GSH) levels in kidney tissues were measured. Liquid chromatography-mass spectrophotometry (LC-MS-MS) was performed to identify the chemical composition of AG extract. Kidney functions, single/double-stranded DNA damage, chromosomal aberrations, mitotic index, MDA and NO levels were significantly (p < 0.001) increased in TBX-treated group compared to the control and AG-treated one. Meanwhile, CAT and GSH activities were significantly diminished and the AG supplementation significantly (p < 0.001) ameliorated these effects compared with the control and AG-treated groups. Five compounds have been identified using GNPS networking including 7,3′,4′-Trihydroxyisoflavone, Noscapine, Tetrahydropapaveroline, Costunolide, Hesperidin. In conclusion, results of the present study suggest that AG exerted a protective role against TBX-induced oxidative stress and genotoxicity which may be attributed to the active metabolites in the gum.
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- El-Sayed, Ashraf S. A., et al.
(författare)
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Aspergillus nidulans thermostable arginine deiminase-Dextran conjugates with enhanced molecular stability, proteolytic resistance, pharmacokinetic properties and anticancer activity
- 2019
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Ingår i: Enzyme and microbial technology. - : Elsevier. - 0141-0229 .- 1879-0909. ; 131
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Tidskriftsartikel (refereegranskat)abstract
- The potential anticancer activity of arginine deiminase (ADI) via deimination of L-arginine into citrulline has been extensively verified against various arginine-auxotrophic tumors, however, the higher antigenicity, structural instability and in vivo proteolysis are the major challenges that limit this enzyme from further clinical implementation. Since, this clinically applied enzyme was derived from Mycobacterium spp, thus, searching for ADI from eukaryotic microbes "especially thermophilic fungi" could have a novel biochemical conformational and catalytic properties. Aspergillus nidulans ADI was purified with 5.3 folds, with molecular subunit structure 48 kDa and entire molecular mass 120 kDa, ensuring its homotrimeric identity. The peptide fingerprinting analysis revealing the domain Glu(95)-Gly(96)-Gly(97) as the conserved active site of A. nidulans ADI, with higher proximity to Mycobacterium ADI Glade IV. In an endeavor to fortify the structural stability and anticancer activity of A. nidulans ADI, the enzyme was chemically modified with dextran. The optimal activity of Dextran-ADI conjugates was determined at 0.08:20 M ratio of ADI: Dextran, with an overall increase to ADI molecular subunit mass to (similar to)100 kDa. ADI was conjugated with dextran via the a-amino groups interaction of surface lysine residues of ADI. The resistance of Dextran-ADI conjugate to proteolysis had been increased by 2.5 folds to proteinase K and trypsin, suggesting the shielding of > 50% of ADI surface proteolytic recognition sites. The native and Dextran-ADI conjugates have the same optimum reaction temperature (37 degrees C), reaction pH and pH stability (7.0-8.0) with dependency on K+ ions as a cofactor. Dextran-ADI conjugates exhibited a higher thermal stability by (similar to) 2 folds for all the tested temperatures, ensuring the acquired structural and catalytic stability upon dextran conjugation. Dextran conjugation slightly protect the reactive amino and thiols groups of surface amino acids of ADI from amino acids suicide inhibitors. The affinity of ADI was increased by 5.3 folds to free L-arginine with a dramatic reduction in citrullination of peptidylarginine residues upon dextran conjugation. The anticancer activity of ADI to breast (MCF-7), liver (HepG-2) and colon (HCTB, HT29, DLD1 and LS174 T) cancer cell lines was increased by 1.7 folds with dextran conjugation in vitro. Pharmacokinetically, the half-life time of ADI was increased by 1.7 folds upon dextran conjugation, in vivo. From the biochemical and hematological parameters, ADIs had no signs of toxicity to the experimental animals. In addition to the dramatic reduction of L-arginine in serum, citrulline level was increased by 2.5 folds upon dextran conjugation of ADI. This is first report exploring thermostable ADI from thermophilic A. nidulans with robust structural stability, catalytic efficiency and proteolytic resistance.
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