Modulational instability in asymmetric coupled wave functions

The evolution of the amplitude of two nonlinearly interacting waves is considered, via a set of coupled nonlinear Schrödinger-type equations. The dynamical profile is determined by the wave dispersion laws (i.e. the group velocities and the group velocity dispersion terms) and the nonlinearity and coupling coefficients, on which no assumption is made. A generalized dispersion relation is obtained, relating the frequency and wave-number of a small perturbation around a coupled monochromatic (Stokes') wave solution. Explicitly stability criteria are obtained. The analysis reveals a number of possibilities. Two (individually) stable systems may be destabilized due to coupling. Unstable systems may, when coupled, present an enhanced instability growth rate, for an extended wave number range of values. Distinct unstable wavenumber windows may arise simultaneously.

Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation

In mammals, the ATM (ataxia-telangiectasia-mutated) and ATR (ATM and Rad3-related) protein kinases function as critical regulators of the cellular DNA damage response. The checkpoint functions of ATR and ATM are mediated, in part, by a pair of checkpoint effector kinases termed Chk1 and Chk2. In mammalian cells, evidence has been presented that Chk1 is devoted to the ATR signaling pathway and is modified by ATR in response to replication inhibition and UV-induced damage, whereas Chk2 functions primarily through ATM in response to ionizing radiation (IR), suggesting that Chk2 and Chk1 might have evolved to channel the DNA damage signal from ATM and ATR, respectively. We demonstrate here that the ATR-Chk1 and ATM-Chk2 pathways are not parallel branches of the DNA damage response pathway but instead show a high degree of cross-talk and connectivity. ATM does in fact signal to Chk1 in response to IR. Phosphorylation of Chk1 on Ser-317 in response to IR is ATM-dependent. We also show that functional NBS1 is required for phosphorylation of Chk1, indicating that NBS1 might facilitate the access of Chk1 to ATM at the sites of DNA damage. Abrogation of Chk1 expression by RNA interference resulted in defects in IR-induced S and G(2)/M phase checkpoints; however, the overexpression of phosphorylation site mutant (S317A, S345A or S317A/S345A double mutant) Chk1 failed to interfere with these checkpoints. Surprisingly, the kinase-dead Chk1 (D130A) also failed to abrogate the S and G(2) checkpoint through any obvious dominant negative effect toward endogenous Chk1. Therefore, further studies will be required to assess the contribution made by phosphorylation events to Chk1 regulation. Overall, the data presented in the study challenge the model in which Chk1 only functions downstream from ATR and indicate that ATM does signal to Chk1. In addition, this study also demonstrates that Chk1 is essential for IR-induced inhibition of DNA synthesis and the G(2)/M checkpoint.

Innate host defense functions of secretory leucoprotease inhibitor

Chronic lung diseases such as cystic fibrosis and emphysema are characterized by a protease burden, an infective process and a dominant proinflammatory profile. Secretory leucoprotease inhibitor (SLPI) is a prominent innate immune protein of the respiratory tract, possessing serine protease inhibitor activity, antibacterial activity, and anti-inflammatory/immunomodulatory activity. In the course of this review, the authors highlight the findings from a range of studies that illustrate the multiple functions of SLPI and its role in the resolution of the immune response.

STO and GTO field-induced polarization functions for H to Kr

Field-induced polarization (FIP) functions were proposed over two decades ago to improve the accuracy of calculated response properties, and the FIP functions in GTO form for H and C to F were tested on small molecules, with encouraging results. The concept of FIP,is now extended to all atoms up to Kr. New simplifying approximations for the description of asymptotic highest occupied atomic orbitals. (HOAOs) are introduced in this study. They provide the basis for STO and GTO exponents of a complete set of FIP functions from H to Kr, which are both listed for the convenience of the users. Tests on the polarizabilities of a series of atoms and molecules demonstrate that addition of the FIP basis functions to a series' of standard basis sets drastically improves the performance of all these basis sets compared to converged results. Moreover, the byproduct of this study (approximate asymptotic HOAOs) provides information for the construction of accurate basis sets for long-range ground state properties. (C) 2003 Wiley Periodicals, Inc.

Changing attitudes to gender roles: A longitudinal analysis of ordinal response data from the British household panel study

This article examines changes in attitudes to gender roles in contemporary Britain by using a first-order Markov process in which cumulative transition probabilities are logistic functions of a set of personal and socioeconomic characteristics of respondents. The data are taken from the British Household Panel Study (BHPS). The attitudinal responses examined take the form of ordinal responses concerning gender roles in 1991 and 2003. The likelihood function is partitioned to make possible the use of existing software for estimating model parameters. For the BHPS data, it was found that, depending on the value of the response in 1991, a variety of factors were important determinants of attitudes to gender roles by 2003.

Proteomic analysis reveals oxidative stress response as the main adaptative physiological mechanism in cows under different production systems

Three groups of cows representing three ranges of welfare in the production system were included in the study: two groups of Bruna dels Pirineus beef cattle maintained under different management systems (good and semiferal conditions) and a group of Alberes cows, a breed that lives in the mountains (hardest conditions).

In order to identify new stress/welfare biomarkers, serum from Bruna cows living in both environments was subjected to DIGE labelling, two-dimensional electrophoresis and MALDI-MS or ion trap MS. Identification was achieved for 15 proteins, which mainly belonged to three biological functions, the oxidative stress pathway (glutathione peroxidase (GPx) and paraoxonase (PON-1)), the acute phase protein family (Heremans Schmid glycoprotein alpha2 (α2-HSG)) and the complement system.

Biological validation included the Alberes breed. GPx and PON-1 were validated by an enzymatic assay and found to be higher and lower, respectively, in cows living in hard conditions. α2-HSG was validated by ELISA and found to be reduced in hard conditions. Other biomarkers of the redox status were also altered by living conditions: protein carbonyl content, superoxide dismutase (SOD) and glutathione reductase (GR).

Our results show that changes in the redox system are the main adaptation of cows living in challenging environmental conditions. This article is part of a Special Issue entitled: “Farm animal proteomics”.

A Spherical Array Approach for Simulation of Binaural Impulse Responses using the Finite Difference Time Domain Method

The finite difference time domain (FDTD) method has direct applications in musical instrument modeling, simulation of environmental acoustics, room acoustics and sound reproduction paradigms, all of which benefit from auralization. However, rendering binaural impulse responses from simulated
data is not straightforward to accomplish as the calculated pressure at FDTD grid nodes does not contain any directional information. This paper addresses this issue by introducing a spherical array to capture sound pressure on a finite difference grid, and decomposing it into a plane-wave density
function. Binaural impulse responses are then constructed in the spherical harmonics domain by combining the decomposed grid data with free field head-related transfer functions. The effects of designing a spherical array in a Cartesian grid are studied, and emphasis is given to the relationships
between array sampling and the spatial and spectral design parameters of several finite-difference
schemes.

Applications of the generalized Langevin equation: Towards a realistic description of the baths

The generalized Langevin equation (GLE) method, as developed previously [L. Stella et al., Phys. Rev. B 89, 134303 (2014)], is used to calculate the dissipative dynamics of systems described at the atomic level. The GLE scheme goes beyond the commonly used bilinear coupling between the central system and the bath, and permits us to have a realistic description of both the dissipative central system and its surrounding bath. We show how to obtain the vibrational properties of a realistic bath and how to convey such properties into an extended Langevin dynamics by the use of the mapping of the bath vibrational properties onto a set of auxiliary variables. Our calculations for a model of a Lennard-Jones solid show that our GLE scheme provides a stable dynamics, with the dissipative/relaxation processes properly described. The total kinetic energy of the central system always thermalizes toward the expected bath temperature, with appropriate fluctuation around the mean value. More importantly, we obtain a velocity distribution for the individual atoms in the central system which follows the expected canonical distribution at the corresponding temperature. This confirms that both our GLE scheme and our mapping procedure onto an extended Langevin dynamics provide the correct thermostat. We also examined the velocity autocorrelation functions and compare our results with more conventional Langevin dynamics.

Brca1 and brca2:Role in the DNA damage response, cancer formation and treatment

BRCA1 and BRCA2 are highly penetrant breast and ovarian cancer susceptibility genes that are mutated in a significant proportion of familial breast and ovarian cancer syndromes. Both of these genes are tumour suppressors, the products of which play vital roles in the cellular response to DNA damage. These proteins function in a number of cellular pathways in order to maintain genomic stability including DNA damage signaling, DNA repair, cell cycle regulation, protein ubiquitination, chromatin remodeling, transcriptional regulation and apoptosis. This chapter will discuss the functions of these proteins and how they relate to tumour development, and therapy. © 2009 Springer Science+Business Media B.V.

Nuclear translocation and functions of growth factor receptors

Cellular signal transduction in response to environmental signals involves a relay of precisely regulated signal amplifying and damping events. A prototypical signaling relay involves ligands binding to cell surface receptors and triggering the activation of downstream enzymes to ultimately affect the subcellular distribution and activity of DNA-binding proteins that regulate gene expression. These so-called signal transduction cascades have dominated our view of signaling for decades. More recently evidence has accumulated that components of these cascades can be multifunctional, in effect playing a conventional role for example as a cell surface receptor for a ligand whilst also having alternative functions for example as transcriptional regulators in the nucleus. This raises new challenges for researchers. What are the cues/triggers that determine which role such proteins play? What are the trafficking pathways which regulate the spatial distribution of such proteins so that they can perform nuclear functions and under what circumstances are these alternative functions most relevant?

Studies of epithelial response to streptozotocin-induced hyperglycemia

A hiperglicemia é a principal característica da diabetes mellitus (DM), uma das causas de morte que mais cresce em Portugal, e cujas complicações a longo prazo são mais debilitantes e mais sobrecarregam os sistemas de saúde. No entanto, os mecanismos subjacentes à resposta fisiológica de alguns tecidos à hiperglicemia não estão completamente esclarecidos. Este estudo teve como objetivo avaliar de que forma o tempo de exposição à hiperglicemia afeta dois tecidos epiteliais, o endotélio e as glândulas salivares, que são frequentemente associados a complicações da DM, utilizando um modelo animal. Adicionalmente, procurou-se encontrar novos biomarcadores para avaliar a suscetibilidade a complicações orais em diabéticos, analisando as modificações pós-traducionais (PTMs) da família de proteínas mais representativa na saliva humana: proteínas ricas em prolina (PRPs). A disfunção vascular está na origem de várias complicações da diabetes. Neste sentido, observou-se uma progressiva disfunção endotelial com o aumento do tempo de exposição à hiperglicemia, que resulta do aumento de danos no endotélio e da diminuição da capacidade de mobilização de células progenitoras. Simultaneamente, o aumento observado na atividade da via de ativação do sistema de complemento mediada por lectinas (MBL), sugere um envolvimento do sistema de imunidade inata na patogénese da disfunção vascular. Outra complicação comum da DM é o desenvolvimento de doenças orais, nomeadamente as relacionadas com a redução da secreção salivar. Na análise às glândulas submandibulares, observou-se uma resposta inicial à hiperglicemia com fortes variações na expressão de proteínas, mas a longo prazo, estas variações foram atenuadas, sugerindo um mecanismo de adaptação à hiperglicemia crónica. Adicionalmente, as proteínas relacionadas com a secreção, como as anexinas, apresentaram-se sobre-expressas, enquanto as calicreinas e proteínas metabólicas estavam sub-expressas. Estas variações sugerem que, apesar de uma diminuição da capacidade de regeneração, as células tentam superar a perda de tecido por meio do aumento da secreção, embora sem êxito. O comprometimento funcional das glândulas salivares tem consequências na composição e funções da saliva. Analisando as PTMs das PRPs salivares humanas, observou-se um aumento da frequência de péptidos com ciclização de resíduos N-terminais de glutamina a piroglutamato, o que confere uma resistência à atividade proteolítica que, por sua vez, se encontra aumentada em diabéticos. Assim, a presença de péptidos com N-piroglutamato poderá ser um potencial biomarcador da suscetibilidade a complicações orais em diabéticos.

Numerical and combinatorial applications of generalized Appell polynomials

This thesis studies properties and applications of different generalized Appell polynomials in the framework of Clifford analysis. As an example of 3D-quasi-conformal mappings realized by generalized Appell polynomials, an analogue of the complex Joukowski transformation of order two is introduced. The consideration of a Pascal n-simplex with hypercomplex entries allows stressing the combinatorial relevance of hypercomplex Appell polynomials. The concept of totally regular variables and its relation to generalized Appell polynomials leads to the construction of new bases for the space of homogeneous holomorphic polynomials whose elements are all isomorphic to the integer powers of the complex variable. For this reason, such polynomials are called pseudo-complex powers (PCP). Different variants of them are subject of a detailed investigation. Special attention is paid to the numerical aspects of PCP. An efficient algorithm based on complex arithmetic is proposed for their implementation. In this context a brief survey on numerical methods for inverting Vandermonde matrices is presented and a modified algorithm is proposed which illustrates advantages of a special type of PCP. Finally, combinatorial applications of generalized Appell polynomials are emphasized. The explicit expression of the coefficients of a particular type of Appell polynomials and their relation to a Pascal simplex with hypercomplex entries are derived. The comparison of two types of 3D Appell polynomials leads to the detection of new trigonometric summation formulas and combinatorial identities of Riordan-Sofo type characterized by their expression in terms of central binomial coefficients.

Oxidation and glycoxidation of phosphatidylserine and their effect in immune response : a lipidomic approach

Phosphatidylserine (PS) is a member of the class of phospholipids, and is distributed among all cells of mammalians, playing important roles in diverse biological processes, including blood clotting and apoptosis. When externalized, PS is a ligand that is recognized on apoptotic cells. It has been considered that before externalization PS is oxidized and oxPS enhance the recognition by macrophages receptors, however the knowledge about oxidation of PS is still limited. PS, like others phospholipids, has two fatty acyl chains and one polar head group, in this case is the amino acid serine. The modifications in PS structure can occur by oxidation of the unsaturated fatty acyl chains and by glycation of the polar head group, due to free amine group, thus increasing the susceptibility to oxidative events. The main goal of this work was to characterize and identify oxidized and glycoxidized PS, contributing to the knowledge of the biological role of oxidation products of PS, as well as of glycated PS, in immune and inflammatory processes. To achieve this goal, PS standards (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho- L-serine (POPS), 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine (DPPS), 1- palmitoyl-2-linoleoyl-sn-glycero-3-phospho-L-serine (PLPS) and 1-palmitoyl-2- arachidonoyl-sn-glycero-3-phospho-L-serine (PAPS)) and glycated PS (PAPS and POPS) were induced to oxidize in model systems, using different oxidant reagents: HO• and 2,2'-azobis-2-methyl-propanimidamide dihydrochloride (AAPH) . The detailed structural characterization of the oxidative products was performed by ESI-MS and MS/MS coupled to separation techniques such as off line TLC-MS and on line LC-MS, in order to obtained better characterization of the larger number of PS and glycated PS oxidation products. The results obtained in this work allowed to identify several oxidation products of PS and glycated PS with modifications in unsaturated fatty acyl chain. Also, oxidation products formed due to structural changes in the serine polar head with formation of terminal acetamide, terminal hydroperoxyacetaldehyde.and terminal acetic acid (glycerophosphacetic acid, GPAA) were identified. The mass spectrometric specific fragmentation pathway of each type of oxidation product was determined using different mass spectrometry approaches. Based on the identified fragmentation pathways, targeted lipidomic analysis was performed to detect oxidation products modified in serine polar head in HaCaT cell line treated with AAPH. The GPAA was detected in HaCaT cells treated with AAPH to induce oxidative stress, thus confirming that modifications in PS polar head is possible to occur in biological systems. Furthermore, it was found that glycated PS species are more prone to oxidative modifications when compared with non glycated PS. During oxidation of glycated PS, besides the oxidation in acyl chains, new oxidation products due to oxidation of the glucose moiety were identified, including PS advanced glycation end products (PSAGES). To investigate if UVA oxidative stress exerted changes in the lipidome of melanoma cell lines, particularly in PS profile, a lipidomic analysis was performed. The lipid profile was obtained using HILIC-LC-MS and GC-MS analysis of the total lipid extracts obtained from human melanoma cell line (SKMEL- 28) after UVA irradiation at 0, 2 and 24 hours. The results did not showed significant differences in PS content. At molecular level, only PS (18:0:18:1) decreased at the moment of irradiation. The most significant changes in phospholipids content occurred in phosphatidylcholines (PC) and phosphatidylinositol (PI) classes, with an increase of mono-unsaturated fatty acid (MUFA), similarly as observed for the fatty acid analysis. Overall, these data indicate that the observed membrane lipid changes associated with lipogenesis after UVA exposure may be correlated with malignant transformations associated with cancer development and progression. Despite of UVA radiation is associated with oxidative damage, in this work was not possible observe oxidation phospholipids. The anti/pro-inflammatory properties of the oxidized PLPS (oxPLPS) versus non-oxidized PLPS were tested on LPS stimulated RAW 264.7 macrophages. The modulation of intracellular signaling pathways such as NF-kB and MAPK cascades by oxPLPS and PS was also examined in this study. The results obtained from evaluation of anti/pro-inflammatory properties showed that neither PLPS or oxPLPS species activated the macrophages. Moreover only oxidized PLS were found to significantly inhibit NO production and iNOS and il1β gene transcription induced by LPS. The analysis at molecular level showed that this was the result of the attenuation of LPS-induced c-Jun-N-terminal kinase (JNK) and p65 NF-kB nuclear translocation. Overall these data suggest that oxPLPS, but not native PLPS, mitigates pro-inflammatory signaling in macrophages, contributing to containment of inflammation during apoptotic cell engulfment. The results obtained in this work provides new information on the modifications of PS, facilitating the identification of oxidized species in complex samples, namely under physiopathologic conditions and also contributes to a better understanding of the role of oxPS and PS in the inflammatory response, in the apoptotic process and other biological functions.

Higher order derivatives and norms of certain matrix functions

Tese de doutoramento, Matemática (Álgebra Lógica e Fundamentos), Universidade de Lisboa, Faculdade de Ciências, 2014

Regulatory interactions between the metabolic sensors SIRT1 and AMPK in modulating PPARα linked functions, in obesity-dependent type 2 diabetes mellitus

Tese de doutoramento, Ciências Biomédicas (Ciências Funcionais), Universidade de Lisboa, Faculdade de Medicina, 2014