An open and parallel multiresolution framework using block-based adaptive grids

A numerical approach for solving evolutionary partial differential equations in two and three space dimensions on block-based adaptive grids is presented. The numerical discretization is based on high-order, central finite-differences and explicit time integration. Grid refinement and coarsening are triggered by multiresolution analysis, i.e. thresholding of wavelet coefficients, which allow controlling the precision of the adaptive approximation of the solution with respect to uniform grid computations. The implementation of the scheme is fully parallel using MPI with a hybrid data structure. Load balancing relies on space filling curves techniques. Validation tests for 2D advection equations allow to assess the precision and performance of the developed code. Computations of the compressible Navier-Stokes equations for a temporally developing 2D mixing layer illustrate the properties of the code for nonlinear multi-scale problems. The code is open source

Inconsistency in the Diagnosis of Functional Heartburn: Usefulness of Prolonged Wireless pH Monitoring in Patients With Proton Pump Inhibitor Refractory Gastroesophageal Reflux Disease

Background/Aims The diagnosis of functional heartburn is important for management, however it stands on fragile pH monitoring variables, ie, acid exposure time varies from day to day and symptoms are often few or absent. Aim of this study was to investigate consistency of the diagnosis of functional heartburn in subsequent days using prolonged wireless pH monitoring and its impact on patients' outcome. Methods Fifty proton pump inhibitotor refractory patients (11 male, 48 years [range, 38-57 years]) with a diagnosis of functional heartburn according to Rome III in the first 24 hours of wireless pH monitoring were reviewed. pH variables were analysed in the following 24-hour periods to determine if tracings were indicative of diagnosis of non-erosive reflux disease (either acid exposure time > 5% or normal acid exposure time and symptom index >= 50%). Outcome was assessed by review of hospital files and/or telephone interview. Results Fifteen out of 50 patients had a pathological acid exposure time after the first day of monitoring (10 in the second day and 5 in subsequent days), which changed their diagnosis from functional heartburn to non-erosive reflux disease. Fifty-four percent of non-erosive reflux disease vs 11% of functional heartburn patients (P < 0.003) increased the dose of proton pump inhibitors or underwent fundoplication after the pH test. Outcome was positive in 77% of non-erosive reflux disease vs 43% of functional heartburn patients (P < 0.05). Conclusions One-third of patients classified as functional heartburn at 24-hour pH-monitoring can be re-classified as non-erosive reflux disease after a more prolonged pH recording period. This observation has a positive impact on patients' management

Translocating the blood-brain barrier using electrostatics

Copyright © 2012 Ribeiro,Domingues, Freire,Santos and Castanho. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.Mammalian cell membranes regulate homeostasis, protein activity, and cell signaling. The charge at the membrane surface has been correlated with these key events. Although mammalian cells are known to be slightly anionic, quantitative information on the membrane charge and the importance of electrostatic interactions in pharmacokinetics and pharmacodynamics remain elusive. Recently, we reported for the first time that brain endothelial cells (EC) are more negatively charged than human umbilical cord cells, using zeta-potential measurements by dynamic light scattering. Here, we hypothesize that anionicity is a key feature of the blood-brain barrier (BBB) and contributes to select which compounds cross into the brain. For the sake of comparison, we also studied the membrane surface charge of blood components—red blood cells (RBC), platelets, and peripheral blood mononuclear cells (PBMC).To further quantitatively correlate the negative zeta-potential values with membrane charge density, model membranes with different percentages of anionic lipids were also evaluated. From all the cells tested, brain cell membranes are the most anionic and those having their lipids mostly exposed, which explains why lipophilic cationic compounds are more prone to cross the blood-brain barrier.Fundação para a Ciência e Tecnologia — Ministério da Educação e Ciência (FCT-MEC, Portugal) is acknowledged for funding (including fellowships SFRH/BD/42158/2007 to Marta M.B. Ribeiro, SFRH/BD/41750/2007 to Marco M. Domingues and SFRH/BD/70423/2010 to João M. Freire) and project PTDC/QUI-BIQ/119509/2010. Marie Curie Industry-Academia Partnerships and Pathways (European Commission) is also acknowledged for funding (FP7-PEOPLE-2007-3-1-IAPP, Project 230654)

Fermentation of high concentrations of lactose to ethanol by engineered flocculent saccharomyces cerevisiae

The development of microorganims that efficiently ferment lactose has a high biotechnological interest, particularly for cheese whey bioremediation processes with simultaneous bio-ethanol production. The lactose fermentation performance of a recombinant Saccharomyces cerevisiae flocculent strain was evaluated. The yeast consumed rapidly and completely lactose concentrations up to 150 g l-1 in either well- or micro-aerated batch fermentations. The maximum ethanol titre was 8% (v/v) and the highest ethanol productivity was 1.5–2 g l-1 h-1, in micro-aerated fermentations. The results presented here emphasise that this strain is an interesting alternative for the production of ethanol from lactose-based feedstocks.Fundação para a Ciência e a Tecnologia (FCT

Alcoholic fermentation of lactose by engineered flocculent Saccharomyces cerevisiae

The construction of Saccharomyces cerevisiae strains with the ability to ferment lactose has biotechnological interest, particularly for cheese whey fermentation to ethanol. Direct fermentation of whey to ethanol is generally not economically feasible because the low lactose content (ca. 5% w/v) results in low ethanol titre (2 – 3% v/v), making the distillation process too expensive. Concentration of whey lactose (e.g. by ultrafiltration) prior to fermentation is an option to obtain higher ethanol titres. Microbial strains are therefore needed that can efficiently convert high concentrations of lactose into ethanol. We describe here the engineering of a S. cerevisiae strain for efficient lactose fermentation, involving genetic and evolutionary engineering strategies. The evolved strain obtained fermented efficiently lactose concentrations up to 150 g L-1, including 3-fold concentrated cheese whey, producing ethanol titres up to 8% v/v. The strain is highly flocculent, a property that makes it particularly suitable for the development of high cell density fermentation processes

Fermentation of lactose to bio-ethanol by yeasts as part of integrated solutions for the valorisation of cheese whey

Cheese whey, the main dairy by-product, is increasingly recognized as a source of many bioactive valuable compounds. Nevertheless, the most abundant component in whey is lactose (ca. 5% w/v), which represents a significant environmental problem. Due to the large lactose surplus generated, its conversion to bio-ethanol has long been considered as a possible solution for whey bioremediation. In this review, fermentation of lactose to ethanol is discussed, focusing on wild lactose-fermenting yeasts, particularly Kluyveromyces marxianus, and recombinant Saccharomyces cerevisiae strains. The early efforts in the screening and characterization of the fermentation properties of wild lactose-consuming yeasts are reviewed. Furthermore, emphasis is given on the latter advances in engineering S. cerevisiae strains for efficient whey-to-ethanol bioprocesses. Examples of industrial implementation are briefly discussed, illustrating the viability of whey-to-ethanol systems. Current developments on strain engineering together with the growing market for biofuels will likely boost the industrial interest in such processes.Fundação para a Ciência e a Tecnologia (FCT) - Projecto ProBioethanol PTDC/BIO/66151/2006 ; bolsa SFRH/BD/13463/2003 and SFRH/BPD/44328/200

Lactose fermentation by recombinant Saccharomyces cerevisiae strains

The development of Saccharomyces cerevisiae strains with the ability to ferment lactose has a high biotechnological interest, particularly for cheese whey bioremediation processes with simultaneous bio-ethanol production. We have developed a flocculent S. cerevisiae strain that efficiently ferments lactose to ethanol, using a combination of genetic engineering and evolutionary engineering approaches. This strain fermented efficiently and nearly completely (residual lactose < 3 g·L -1) lactose concentrations up to 150 g·L-1, including 3-fold concentrated cheese whey, producing ethanol titres up to 8% (v/v). The ethanol productivity obtained with this strain (> 1.5 g·L -1·h-1) was higher than that reported for batch or fed-batch fermentations with other lactose-consuming recombinant S. cerevisiae strains. The strain is highly flocculent, a property that makes it interesting for the development of high cell density fermentation processes, which may attain much higher productivity

Cleavages of photochromic compounds derived from heterocycles under electrospray tandem mass spectrometry : study of the influence of the heteroatom in fragmentation mechanisms

In this paper we report the fragmentation pathways of chromenes derived from carbazole, dibenzofuran and dibenzothiophene, under ESI-MS/MS experimental conditions, and their relationship with structural features, specially focused on the heteroatom’s effect on the fragmentation mechanisms.Fundação para a Ciência e Tecnologia (FCT

Lipoxidation and cancer immunity

Lipoxidation is a well-known reaction between electrophilic carbonyl species, formed during oxidation of lipids, and specific proteins that, in most cases, causes an alteration in proteins function. This can occur under physiological conditions but, in many cases, it has been associated to pathological process, including cancer. Lipoxidation may have an effect in cancer development through their effects in tumour cells, as well as through the alteration of immune components and the consequent modulation of the immune response. The formation of protein adducts affects different proteins in cancer, triggering different mechanism, such as proliferation, cell differentiation and apoptosis, among others, altering cancer progression. The divergent results obtained documented that the formation of lipoxidation adducts can have either anti-carcinogenic or pro-carcinogenic effects, depending on the cell type affected and the specific adduct formed. Moreover, lipoxidation adducts may alter the immune response, consequently causing either positive or negative alterations in cancer progression. Therefore, in this review, we summarize the effects of lipoxidation adducts in cancer cells and immune components and their consequences in the evolution of different types of cancer.publishe