Steady-state global optimization of metabolic non-linear dynamic models through recasting into power-law canonical models

Background: Design of newly engineered microbial strains for biotechnological purposes would greatly benefit from the development of realistic mathematical models for the processes to be optimized. Such models can then be analyzed and, with the development and application of appropriate optimization techniques, one could identify the modifications that need to be made to the organism in order to achieve the desired biotechnological goal. As appropriate models to perform such an analysis are necessarily non-linear and typically non-convex, finding their global optimum is a challenging task. Canonical modeling techniques, such as Generalized Mass Action (GMA) models based on the power-law formalism, offer a possible solution to this problem because they have a mathematical structure that enables the development of specific algorithms for global optimization. Results: Based on the GMA canonical representation, we have developed in previous works a highly efficient optimization algorithm and a set of related strategies for understanding the evolution of adaptive responses in cellular metabolism. Here, we explore the possibility of recasting kinetic non-linear models into an equivalent GMA model, so that global optimization on the recast GMA model can be performed. With this technique, optimization is greatly facilitated and the results are transposable to the original non-linear problem. This procedure is straightforward for a particular class of non-linear models known as Saturable and Cooperative (SC) models that extend the power-law formalism to deal with saturation and cooperativity. Conclusions: Our results show that recasting non-linear kinetic models into GMA models is indeed an appropriate strategy that helps overcoming some of the numerical difficulties that arise during the global optimization task.

Nitrogênio, fósforo e potássio na nutrição e na produção de mudas de laranjeira 'Valência', enxertada sobre citrumeleiro 'Swingle'

O experimento foi conduzido em estufa telada na FCAV/Unesp Câmpus Jaboticabal-SP, durante o período de novembro de 2005 a janeiro de 2007. O estudo teve por objetivo avaliar componentes do desenvolvimento e do estado nutricional de mudas de laranjeira 'Valência', enxertada sobre citrumeleiro 'Swingle', cultivado em substrato, em função de doses de nitrogênio, fósforo e potássio. O delineamento experimental foi o inteiramente casualizado, em esquema fatorial 3³ + 1, sendo 3 fatores (nitrogênio, fósforo e potássio), 3 doses e uma testemunha (sem adubação), com 3 repetições. A unidade experimental foi constituída de uma muda de laranjeira por sacolas de 5 dm-3, contendo 2,5 kg de substrato casca de Pinus e vermiculita. Os tratamentos foram constituídos pela aplicação das seguintes doses de nutrientes em mg por dm³ de substrato: N1/2:459, N1:918 e N2:1836; P1/2:92, P1:184 e P2: 368; K1/2:438, K1:876 e K2:1752. Aos 424 dias após a semeadura, as plantas foram divididas em raízes e parte aérea para a determinação da massa da matéria seca, altura, área foliar, diâmetro do caule e conteúdo de nutrientes. As adubações com N, P e K proporcionaram maior crescimento e maior acúmulo de N, P e K na parte aérea e nas raízes das mudas de laranjeira, em substrato de casca de Pinus e vermiculita, em relação à testemunha. A dose de 459 mg dm-3 de N e as doses de P e K 184 e 876 mg dm-3, respectivamente, proporcionaram melhor crescimento da parte aérea das mudas; porém, na dose recomendada de N de 918 mg dm-3, ocorreu maior crescimento do sistema radicular.

Correlated genetic effects on reproduction define a domestication syndrome in a forest tree.

Compared to natural selection, domestication implies a dramatic change in traits linked to fitness. A number of traits conferring fitness in the wild might be detrimental under domestication, and domesticated species typically differ from their ancestors in a set of traits known as the domestication syndrome. Specifically, trade-offs between growth and reproduction are well established across the tree of life. According to allocation theory, selection for growth rate is expected to indirectly alter life-history reproductive traits, diverting resources from reproduction to growth. Here we tested this hypothesis by examining the genetic change and correlated responses of reproductive traits as a result of selection for timber yield in the tree Pinus pinaster. Phenotypic selection was carried out in a natural population, and progenies from selected trees were compared with those of control trees in a common garden experiment. According to expectations, we detected a genetic change in important life-history traits due to selection. Specifically, threshold sizes for reproduction were much higher and reproductive investment relative to size significantly lower in the selected progenies just after a single artificial selection event. Our study helps to define the domestication syndrome in exploited forest trees and shows that changes affecting developmental pathways are relevant in domestication processes of long-lived plants.

Almoge i Savolax. Les paysans de Savolax - 1

S.l. 1780-l.

Charta öfver Åland med en del af Svenska och Finska skären samt post-vägen imellan Sverige och Finland - [Yleisnäkymä - Overview]

Stockholm : Kongl. landtmäteri contoiret 1789, E. Åkerlund

Allmoge i Karelen. Les paysans de Karelie - 1

S.l. 1780-l.

Almoge i Savolax. Les paysans de Savolax - 1mv

S.l. 1780-l.

Allmoge i Karelen. Les paysans de Karelie - 1mv

S.l. 1780-l.

Lymphoepithelial carcinoma in the maxillary sinus: a case report.

INTRODUCTION: Lymphoepithelial carcinoma of the maxillary sinus is a very rare malignancy and it can be difficult to make a pre-operative diagnosis. CASE PRESENTATION: A 72-year-old Caucasian woman presented to our facility with an isolated right-side epistaxis that had been present for three months, with the results of a computed tomography scan showing a soft tissue mass in the right maxillary sinus with an impacted tooth. The results of a transnasal endoscopic biopsy were compatible with a lymphoepithelial carcinoma, following which our patient underwent a radical excision of the mass. The final histology results revealed lymphoepithelial carcinoma of the maxillary sinus with negative assays for Epstein-Barr virus. Our patient was given post-operative external radiotherapy and has remained disease-free at three-year follow-up. CONCLUSIONS: This report details the diagnosis and management of a case of lymphoepithelial carcinoma of the maxillary sinus, which is a very rare malignant tumor with very little mention in the literature. Only a strong suspicion with systematic use of various patho-immunological tests helps to arrive at a definitive diagnosis by excluding other better-known tumors.

Subcellular Redistribution of Root Aquaporins Induced by Hydrogen Peroxide.

Aquaporins are water channel proteins that mediate the fine-tuning of cell membrane water permeability during development or in response to environmental stresses. The present work focuses on the oxidative stress-induced redistribution of plasma membrane intrinsic protein (PIP) aquaporins from the plasma membrane (PM) to intracellular membranes. This process was investigated in the Arabidopsis root. Sucrose density gradient centrifugation showed that exposure of roots to 0.5 mM H2O2 induces significant depletion in PM fractions of several abundant PIP homologs after 15 min. Analyses by single-particle tracking and fluorescence correlative spectroscopy showed that, in the PM of epidermal cells, H2O2 treatment induces an increase in lateral motion and a reduction in the density of a fluorescently tagged form of the prototypal AtPIP2;1 isoform, respectively. Co-expression analyses of AtPIP2;1 with endomembrane markers revealed that H2O2 triggers AtPIP2;1 accumulation in the late endosomal compartments. Life-time analyses established that the high stability of PIPs was maintained under oxidative stress conditions, suggesting that H2O2 triggers a mechanism for intracellular sequestration of PM aquaporins without further degradation. In addition to information on cellular regulation of aquaporins, this study provides novel and complementary insights into the dynamic remodeling of plant internal membranes during oxidative stress responses.

Therapeutic drug monitoring of targeted anticancer therapy.

New oral targeted anticancer therapies are revolutionizing cancer treatment by transforming previously deadly malignancies into chronically manageable conditions. Nevertheless, drug resistance, persistence of cancer stem cells, and adverse drug effects still limit their ability to stabilize or cure malignant diseases in the long term. Response to targeted anticancer therapy is influenced by tumor genetics and by variability in drug concentrations. However, despite a significant inter-patient pharmacokinetic variability, targeted anticancer drugs are essentially licensed at fixed doses. Their therapeutic use could however be optimized by individualization of their dosage, based on blood concentration measurements via the therapeutic drug monitoring (TDM). TDM can increase the probability of therapeutic responses to targeted anticancer therapies, and would help minimize the risk of major adverse reactions.