Activation of the mitogen-activated protein kinase pathway is involved in and sufficient for megakaryocytic differentiation of CMK cells

Activation of the mitogen-activated protein (MAP) kinase pathway has been associated with both cell proliferation and differentiation. Constitutively activated forms of Mek (MAP kinase/Erk kinase) and Erk (MAP kinase) have been previously shown capable of inducing differentiation or proliferation in nonhematopoietic cells. To specifically examine the role of Erk activation in megakaryocytic growth and development, we activated the MAP kinase pathway by the transfection of constitutively activated Mek or Erk cDNA into a human megakaryoblastic cell line, CMK, by electroporation. The CMK transfectant clones that expressed constitutively activated Mek or Erk showed morphologic changes of differentiation. Transfected cells also showed expression of mature megakaryocytic cell surface markers. The MAP kinase pathway was also activated by treatment of the hematopoietic cells with a cytokine that activates Erk. The treatment of CMK cells with stem cell factor (SCF ) caused MAP kinase activation and induced differentiation by the expression of mature megakaryocytic cell surface markers. The effects of the SCF treatment were inhibited by pretreatment with a specific inhibitor of the MAP kinase pathway, PD98059. In this report, we conclude that activation of the MAP kinase pathway was both necessary and sufficient to induce differentiation in this megakaryoblastic cell line.     

Fluoride exposure in cervids inhabiting areas adjacent to aluminum smelters in Norway. I. Residue levels

Mandibular fluorine concentrations were determined in 1,425 red deer (Cervus elaphus), 240 moose (Alces alces), and 424 roe deer (Capreolus capreolus) collected in Norway from 1990 to 1993 in seven municipalities in which aluminum smelters are located, in eight neighboring municipalities, and in eight reference areas representing background levels. Background fluorine concentration was significantly correlated with age in all three species. Roe deer had the highest mean background fluorine level in each age group, followed by red deer. Due to differences in fluoride exposure, large variations in bone fluorine residues were evident between locations. In Ardal, the district most severely exposed to fluoride contamination, nine of ten cervids had fluorine concentrations exceeding background levels. The proportions of red deer with fluorine residues exceeding background levels also were high in neighboring municipalities to Ardal. We propose that roe deer are a better biomonitor of local fluoride exposure than red deer and moose, due to their more sedentary behavior.     

Robust pose estimation and recognition using non-gaussian modeling of appearance subspaces

We present an original appearance model that generalizes the usual Gaussian visual subspace model to non-Gaussian and nonparametric distributions. It can be useful for the modeling and recognition of images under difficult conditions such as large occlusions and cluttered backgrounds. Inference under the model is efficiently solved using the mean shift algorithm     

Learning automata-based solutions to the nonlinear fractional knapsack problem with applications to optimal resource allocation.

This paper considers the nonlinear fractional knapsack problem and demonstrates how its solution can be effectively applied to two resource allocation problems dealing with the World Wide Web. The novel solution involves a "team" of deterministic learning automata (LA). The first real-life problem relates to resource allocation in web monitoring so as to "optimize" information discovery when the polling capacity is constrained. The disadvantages of the currently reported solutions are explained in this paper. The second problem concerns allocating limited sampling resources in a "real-time" manner with the purpose of estimating multiple binomial proportions. This is the scenario encountered when the user has to evaluate multiple web sites by accessing a limited number of web pages, and the proportions of interest are the fraction of each web site that is successfully validated by an HTML validator. Using the general LA paradigm to tackle both of the real-life problems, the proposed scheme improves a current solution in an online manner through a series of informed guesses that move toward the optimal solution. At the heart of the scheme, a team of deterministic LA performs a controlled random walk on a discretized solution space. Comprehensive experimental results demonstrate that the discretization resolution determines the precision of the scheme, and that for a given precision, the current solution (to both problems) is consistently improved until a nearly optimal solution is found--even for switching environments. Thus, the scheme, while being novel to the entire field of LA, also efficiently handles a class of resource allocation problems previously not addressed in the literature.     

Structural vulnerability of energy distribution systems: Incorporating infrastructural dependencies

In this paper a novel method for assessing the structural vulnerability of two coupled energy distribution systems is presented. The co-existing of an electric power distribution system and a district heating system is described and modelled, under the assumption that the operation of the district heating system is directly dependent on electric power. The structural vulnerability of the two systems subject to single failures or a set of simultaneous failures in the power system is found. Thus, the consequences of power system failures for the energy supply as a whole are quantified.     

Industrial aspects and literature survey: Combined inventory management and routing

This paper describes industrial aspects of combined inventory management and routing in maritime and road-based transportation, and gives a classification and comprehensive literature review of the current state of the research.The literature is contrasted with aspects of industrial applications from a constructive, but critical, viewpoint. Based on the status and trends within the field, future research is suggested with regard to both further development of the research area and industrial needs. By highlighting the industrial aspects, practitioners will hopefully see the benefit of using advanced decision support systems in complex situations related to combined inventory management and routing in their business. In addition, a classification and presentation of the research should help and motivate researchers to further focus on inventory management and routing challenges.     

Reduced secretion of triacylglycerol in CaCo-2 cells transfected with intestinal fatty acid-binding protein

The fatty acid-binding proteins are hypothesized to be involved in cellular fatty acid transport and trafficking. We established CaCo-2 cells stably transfected with intestinal fatty acid-binding protein (I-FABP) and examined how the expression of this protein may influence fatty acid metabolism. I-FABP expression was detectable in I-FABP-transfected cells, whereas parent CaCo-2 cells as well as mock-transfected cells failed to express detectable levels of I-FABP mRNA or protein at any stage of differentiation. For studies of lipid metabolism, cells were incubated with [¹⁴C]oleic acid in taurocholate micelles containing monoolein, and distribution of labeled fatty acid in cellular and secreted lipids was examined. In one transfected cell clone, expressing the highest level of I-FABP, labeled cellular triacylglycerol increased approximately twofold as compared to control cells. The level of intracellular triacylglycerol in two other I-FABP-transfected clones resembled that of control cells. However, secretion of triacylglycerol was markedly reduced in all the I-FABP-expressing cell lines. Our data suggest that increased expression of I-FABP leads to reduced triacylglycerol secretion in intestinal cells.     

Eicosapentaenoic and docosahexaenoic acid affect mitochondrial and peroxisomal fatty acid oxidation in relation to substrate preference

Decreased triacylglycerol synthesis within hepatocytes due to decreased diacylglycerol acyltransferase (DGAT) activity has been suggested to be an important mechanism by which diets rich in fish oil lower plasma triacylglycerol levels. New findings suggest that eicosapentaenoic acid (EPA), and not docosahexaenoic acid (DHA), lowers plasma triacylglycerol by increased mitochondrial fatty acid oxidation and decreased availability of fatty acids for triacylglycerol synthesis. To contribute to the understanding of the triacylglycerol-lowering mechanism of fish oil, the different metabolic properties of EPA and DHA were studied in rat liver parenchymal cells and isolated rat liver organelles. EPA-CoA was a poorer substrate than DHA-CoA for DGAT in isolated rat liver microsomes, and in the presence of EPA, a markedly lower value for the triacyl[³H]glycerol/diacyl[³H]glycerol ratio was observed. The distribution of [1-¹⁴C]palmitic acid was shifted from incorporation into secreted glycerolipids toward oxidation in the presence of EPA (but not DHA) in rat liver parenchymal cells. [1-¹⁴C]EPA was oxidized to a much greater extent than [1-¹⁴C]DHA in rat liver parenchymal cells, isolated peroxisomes, and especially in purified mitochondria. As the oxidation of EPA was more effective and sensitive to the CPT-I inhibitor, etomoxir, when measured in a combination of both mitochondria and peroxisomes, we hypothesized that both are involved in EPA oxidation, whereas DHA mainly is oxidized in peroxisomes. In rats, EPA treatment lowered plasma triacylglycerol and increased hepatic mitochondrial fatty acid oxidation and carnitine palmitoyltransferase (CPT)-I activity in both the presence and absence of malonyl-CoA. Whereas only EPA treatment increased the mRNA levels of CPT-I, DHA treatment increased the mRNA levels of peroxisomal fatty acyl-CoA oxidase and fatty acid binding protein more effectively than EPA treatment. In conclusion, EPA and DHA affect cellular organelles in relation to their substrate preference. The present study strongly supports the hypothesis that EPA, and not DHA, lowers plasma triacylglycerol by increased mitochondrial fatty acid oxidation.     

Industrial aspects and literature survey: Fleet composition and routing

The purpose of this paper is to describe industrial aspects of combined fleet composition and routing in maritime and road-based transportation, and to present the current status of research in the form of a comprehensive literature review. First, presents a classification of problems, and then focuses on a basic definition of combined fleet composition and routing: the fleet size and mix vehicle routing problem. A basic mathematical formulation from the literature is presented. Further, the literature of extended and related problems is described and categorized. Surveys of application oriented research in road-based and maritime transportation conclude the review. Finally, we contrast the literature with aspects of industrial applications from a critical, but constructive stance. Major issues for future work are suggested.     

Hypothesized simple factor structure for the Alcohol Expectancy Questionnaire: Confirmatory factor analysis.

This study proposed and tested a theoretical factor structure for the Alcohol Expectancy Questionnaire (AEQ; S. A. Brown, M. S. Goldman, A. Inn, & L. R. Anderson [see record 1981-01217-001]). Factors were hypothesized to (a) reflect either positive or negative reinforcement, and (b) target either personal feelings or social contexts, resulting in 4 hypothesized factors (Social Enhancement, Social Coping, Personal Enhancement, Personal Coping). Participants were 180 male and 226 female undergraduates who completed the AEQ and additional self-report measures. Confirmatory factor analysis revealed that the hypothesized model fit the data. Post hoc adjustments further improved the model. Finally, a higher order factor model fit the data best. Factors correlated in hypothesized ways with other measures: (a) Only Personal Coping expectancies correlated with negative affect; (b) self-efficacy to resist drinking for emotional relief correlated highest with Personal Coping; and (c) self-efficacy to resist social pressure to drink correlated highest with Social Enhancement. Correlations with B. C. Leigh and A. W. Stacy's (see record 1993-35856-001) Drinking Expectancy Questionnaire indicated congruent and divergent validity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)