Box-Cox Transformations and Bias Reduction in Extreme Value Theory

The Box-Cox transformations are used to make the data more suitable for statistical analysis. We know from the literature that this transformation of the data can increase the rate of convergence of the tail of the distribution to the generalized extreme value distribution, and as a byproduct, the bias of the estimation procedure is reduced. The reduction of bias of the Hill estimator has been widely addressed in the literature of extreme value theory. Several techniques have been used to achieve such reduction of bias, either by removing the main component of the bias of the Hill estimator of the extreme value index (EVI) or by constructing new estimators based on generalized means or norms that generalize the Hill estimator. We are going to study the Box-Cox Hill estimator introduced by Teugels and Vanroelen, in 2004, proving the consistency and asymptotic normality of the estimator and addressing the choice and estimation of the power and shift parameters of the Box-Cox transformation for the EVI estimation. The performance of the estimators under study will be illustrated for finite samples through small-scale Monte Carlo simulation studies

The Use of Generalized Means in the Estimation of the Weibull Tail Coefficient

Due to the specificity of the Weibull tail coefficient, most of the estimators available in the literature are based on the log excesses and are consequently quite similar to the estimators used for the estimation of a positive extreme value index. The interesting performance of estimators based on generalized means leads us to base the estimation of the Weibull tail coefficient on the power mean-of-order-. Consistency and asymptotic normality of the estimators under study are put forward. Their performance for finite samples is illustrated through a Monte Carlo simulation. It is always possible to find a negative value of (contrarily to what happens with the mean-of-order- estimator for the extreme value index), such that, for adequate values of the threshold, there is a reduction in both bias and root mean square error

Non-regular Frameworks and the Mean-of-Order p Extreme Value Index Estimation

Most of the estimators of parameters of rare and large events, among which we dis- tinguish the extreme value index (EVI) for maxima, one of the primary parameters in statistical extreme value theory, are averages of statistics, based on the k upper observations. They can thus be regarded as the logarithm of the geometric mean, i.e. the logarithm of the power mean of order p = 0 of a certain set of statistics. Only for heavy tails, i.e. a positive EVI, quite common in many areas of application, and trying to improve the performance of the classical Hill EVI-estimators, instead of the aforementioned geometric mean, we can more generally consider the power mean of order-p (MOp) and build associated MOp EVI-estimators. The normal asymptotic behaviour of MOp EVI-estimators has already been obtained for p < 1/(2ξ), with consistency achieved for p < 1/ξ , where ξ denotes the EVI. We shall now consider the non-regular case, p ≥ 1/(2ξ ), a situation in which either normal or non-normal sum- stable laws can be obtained, together with the possibility of an ‘almost degenerate’ EVI-estimation

Engineering a biosynthetic pathway for high-value glycosaminoglycans production

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3-Aminopyrroles and their application in the synthesis ofpyrrolo[3,2-d]pyrimidine (9-deazapurine) derivatives

3-Aminopyrrole derivatives have been synthesized from 3-anilino-2-cyanoacrylonitrile using Thorpe-Ziegler cyclization. These substituted pyrroles are readily converted into 5H-pyrrolo[3,2- d]pyrimidine (9-deazapurines).FEDERFundação para a Ciência e Tecnologia (FCT

Heterocyclic synthesis with nitriles: synthesis of pyridazine and pyridopyridazine derivatives

The reaction of MND with aryldiazonium chlorides followed by cyclization afforded the pyridazinimine derivatives. Reaction of the latter with another mole of malononitrile produce only pyrido[3,2-c]pyridazine derivatives. Reaction of 4-aminopyridazinone-3- carboxylic acid esters with malononitrile gave only pyridazine-3-carboxylic acid.Fundação para a Ciência e a Tecnologia (FCT) - POCTI-SFA-3-686, SFRH/BPD/31490/2006Fundo Europeu de Desenvolvimento Regional (FEDER

Pathway expression optimization using the Ribosome Binding Site (RBS) Calculator tool

Hydroxycinnamic acids and curcumin are plant metabolites with great therapeutic potential, including anti-inflammatory and anticancer activities. In this study, p-coumaric acid, caffeic acid and curcumin were produced in Escherichia coli using an artificial biosynthetic pathway [1]. Their production was induced by heat using the dnaK and ibpA heat shock promoters [2]. The ribosome binding sites (RBSs) used were tested and further optimized for each gene to assure an efficient translation. To optimize the RBSs we used the bioinformatic design tool RBS Calculator (v1.1) developed by Salis Lab (Penn State University) [3]. This tool predicts the translation initiation rate (TIR) of mRNAs and designs synthetic RBS with specific TIRs. This allows to improve the translation efficiency and to reach a desired response and therefore obtain the expected production using novel genes or biosynthetic pathways. Tyrosine ammonia lyase from Rhodotorula glutinis was used to produce p-coumaric acid from tyrosine. p-Coumaric acid was converted to caffeic acid using 4-coumarate 3-hydroxylase from Saccharothrix espanaensis or cytochrome P450 CYP199A2 from Rhodopseudomonas palustris. Curcumin was produced from ferulic acid using 4-coumarate-CoA ligase from Arabidopsis thaliana, diketide-CoA synthase and curcumin synthase from Curcuma longa. The optimization of the RBSs lead to an increase in the production of p-coumaric acid, caffeic acid and curcumin up to 97.8, 11.7 and 14.4 times, respectively. The highest p-coumaric acid, caffeic acid and curcumin production obtained were 2.5 mM, 370 µM and 17 µM, respectively. These results demonstrate that it is of utmost importance to consider the strength of the RBS when designing a biosynthetic pathway and user-friendly bioinformatic tools such as RBS Calculator can be very useful for that purpose. References: [1] J. L. Rodrigues, M. R. Couto, R. G. Araújo, K. L. J. Prather, L. D. Kluskens, L. R. Rodrigues. Hydroxycinnamic acids and curcumin production in engineered Escherichia coli using heat shock promoters, Biochemical Engineering Journal, 125, 41-49, 2017. [2] J. L. Rodrigues, M. Sousa, K. L. J. Prather, L. D. Kluskens, L. R. Rodrigues. Selection of Escherichia coli heat shock promoters toward their application as stress probes, Journal of Biotechnology, 188, 61-71, 2014. [3] A. E. Borujeni, A. S. Channarasappa, H. M. Salis. Translation rate is controlled by coupled trade-offs between site accessibility, selective RNA unfolding and sliding at upstream standby sites, Nucleic Acids Research, 42, 26462659, 2014.info:eu-repo/semantics/publishedVersio

Synthesis of some novel pyrazolo[3,4-d]pyrimidine derivatives

Reaction of ethyl imidates derived from N-aryl-5-amino-4-cyanopyrazoles with amines or arylhydrazines gave only 4-substituted pyrazolo[3,4-d]pyrimidines, resulting from cyclization followed by Dimroth rearrangement. From the reaction with arylhydrazines, a mixture of the hydrazines and their oxidized forms, the azo products, was obtained. This was proven by an independent synthesis starting from the corresponding 4-chloropyrazolo[3,4-d]pyrimidines as starting material. The structures of the compounds obtained were confirmed by mass spectrometry, 1H and 13C NMR.Fundação para a Ciência e Tecnologia (FCT) - POCTI-SFA-3-686, SFRH/BPD/31490/2006FEDE

Synthesis of novel psoralen analogues and their anti-proliferative effect on human cancer cell lines

We describe the synthesis of 3H-benzofuro[3,2-f]chromen-3-ones. The anti-proliferative effect on human cancer cell lines (MDA-MB231 and HeLa) was evaluated.FCT and FEDER, for National NMR Networ

Development of a sustainable bioprocess for the production of novel Xylooligosaccharides (XOS) and their potential application

The growing demand of novel food products for well-being and age related issues coupled with increasing health care expenditure has attracted global attention on prebiotics. Xylooligosaccarides (XOS) are the only nutraceuticals that can be produced from lignocellulosic biomass. Indeed, XOS can be produced from agricultural crop residues, which is encouraging to the food ingredient industries, as these raw materials are inexpensive, abundant and renewable in nature. XOS beneficial effects include, besides the selective growth stimulation of beneficial gut microflora, enhanced mineral absorption, cholesterol lowering, glucose homeostasis, pathogen exclusion, immune modulation, antioxidant and anticarcinogenic activities, among others. The precursor for XOS is xylan. Xylan is the polysaccharide accounting for 25 to 50% of the dry mass of lignocellulosic-based agriculture residues. XOS can then be produced through chemical or enzymatic processes. The microbial or enzymatic conversion of xylan into value-added useful products, as XOS, holds a great promise for the use of a variety of agro-food and industrial residues. The goal of this PhD project is to develop a sustainable bioprocess by exploring the use of agro-industrial residues for the production of novel XOS and to evaluate their effect on the probiotics viability under simulated gastric conditions. The proposed tasks involve several design and engineering approaches to optimize the production process.info:eu-repo/semantics/publishedVersio