The ecological rationality of explanatory reasoning

There is growing evidence that explanatory considerations influence how people change their degrees of belief in light of new information. Recent studies indicate that this influence is systematic and may result from people’s following a probabilistic update rule. While formally very similar to Bayes’ rule, the rule or rules people appear to follow are different from, and inconsistent with, that better-known update rule. This raises the question of the normative status of those updating procedures. Is the role explanation plays in people’s updating their degrees of belief a bias? Or are people right to update on the basis of explanatory considerations, in that this offers benefits that could not be had otherwise? Various philosophers have argued that any reasoning at deviance with Bayesian principles is to be rejected, and so explanatory reasoning, insofar as it deviates from Bayes’ rule, can only be fallacious. We challenge this claim by showing how the kind of explanation-based update rules to which people seem to adhere make it easier to strike the best balance between being fast learners and being accurate learners. Borrowing from the literature on ecological rationality, we argue that what counts as the best balance is intrinsically context-sensitive, and that a main advantage of explanatory update rules is that, unlike Bayes’ rule, they have an adjustable parameter which can be fine-tuned per context. The main methodology to be used is agent-based optimization, which also allows us to take an evolutionary perspective on explanatory reasoning.     

The IQGAP-related protein DGAP1 mediates signaling to the actin cytoskeleton as an effector and a sequestrator of Rac1 GTPases

Proteins are typically categorized into protein families based on their domain organization. Yet, evolutionarily unrelated proteins can also be grouped together according to their common functional roles. Sequestering proteins constitute one such functional class, acting as macromolecular buffers and serving as an intracellular reservoir ready to release large quantities of bound proteins or other molecules upon appropriate stimulation. Another functional protein class comprises effector proteins, which constitute essential components of many intracellular signal transduction pathways. For instance, effectors of small GTP-hydrolases are activated upon binding a GTP-bound GTPase and thereupon participate in downstream interactions. Here we describe a member of the IQGAP family of scaffolding proteins, DGAP1 from Dictyostelium, which unifies the roles of an effector and a sequestrator in regard to the small GTPase Rac1. Unlike classical effectors, which bind their activators transiently leading to short-lived signaling complexes, interaction between DGAP1 and Rac1-GTP is stable and induces formation of a complex with actin-bundling proteins cortexillins at the back end of the cell. An oppositely localized Rac1 effector, the Scar/WAVE complex, promotes actin polymerization at the cell front. Competition between DGAP1 and Scar/WAVE for the common activator Rac1-GTP might provide the basis for the oscillatory re-polarization typically seen in randomly migrating Dictyostelium cells. We discuss the consequences of the dual roles exerted by DGAP1 and Rac1 in the regulation of cell motility and polarity, and propose that similar signaling mechanisms may be of general importance in regulating spatiotemporal dynamics of the actin cytoskeleton by small GTPases.     

A Study of Melt Flow Analysis of an ABS-Iron Composite in Fused Deposition Modelling Process

Fused deposition modelling (FDM) is a filament based rapid prototyping system which offers the possibility of introducing new composite material for the FDM process as long as the new material can be made in feedstock filament form. Swinburne has been undertaking extensive research in development of new composite materials involving acrylonitrile-butadiene-styrene (ABS) and other materials including metals. In order to predict the behaviour of new ABS based composite materials in the course of FDM process, it is necessary to investigate the flow of the composite material in liquefier head. No such study is available considering the geometry of the liquefier head. This paper presents 2-D and 3-D numerical analysis of melt flow behaviour of a representative ABS-iron composite through the 90-degree bent tube of the liquefier head of the fused deposition modelling process using ANSYS FLOTRAN and CFX finite element packages. Main flow parameters including temperature, velocity, and pressure drop have been investigated. Filaments of the filled ABS have been fabricated and characterized to verify the possibility of prototyping using the new material on the current FDM machine. Results provide promising information in developing the melt flow modelling of metal-plastic composites and in optimising the FDM parameters for better part quality with such composites.     

Project Management Supports (Requisitely) Holistic: Socially Responsible Action in Business Systems

This article emphasizes the role of projects and project management in assuring socially responsible acting of contemporary business systems, presenting some practical applications in the field of tourism. With arising number of projects in business systems and their growing strategic importance, the role of project management has radically been changing for the last two decades. Managing organizations, as a central topic among seven crucial topics in ISO 26000 on social responsibility, is strongly associated with managing projects. Projects have important influence on the established as well as on establishing ongoing operations and are important tools in assuring business systems’ strategic development, by exposing interdependences and supporting the requisitely holistic approach. This article tries to fill the gap we detected in literature on social responsibility where projects and project management seem not to have a proper role. Four different links and interdependencies between project management and systems theory (which ISO 26000 reinforces) are exposed: (1) systemic treatment of project management, (2) systematical treatment of projects as holistic works, (3) systemic treatment of projects as parts of BSs’ strategies, (4) systemic treatment of projects throughout their entire life cycle.     

Complex gas hydrate from the Cascadia margin

Natural gas hydrates are a potential source of energy and may play a role in climate change and geological hazards. Most natural gas hydrate appears to be in the form of 'structure I', with methane as the trapped guest molecule, although 'structure II' hydrate has also been identified, with guest molecules such as isobutane and propane, as well as lighter hydrocarbons. A third hydrate structure, 'structure H', which is capable of trapping larger guest molecules, has been produced in the laboratory, but it has not been confirmed that it occurs in the natural environment. Here we characterize the structure, gas content and composition, and distribution of guest molecules in a complex natural hydrate sample recovered from Barkley canyon, on the northern Cascadia margin. We show that the sample contains structure H hydrate, and thus provides direct evidence for the natural occurrence of this hydrate structure. The structure H hydrate is intimately associated with structure II hydrate, and the two structures contain more than 13 different hydrocarbon guest molecules. We also demonstrate that the stability field of the complex gas hydrate lies between those of structure II and structure H hydrates, indicating that this form of hydrate is more stable than structure I and may thus potentially be found in a wider pressure-temperature regime than can methane hydrate deposits.     

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140?mm?Hg systolic blood pressure or ≥90?mm?Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.     

SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout

Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200-500 microM) compared with other mammals (3-120 microM). About 70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human population, impaired renal excretion leads to hyperuricemia. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes.     

Regulatory networks define phenotypic classes of human stem cell lines

Stem cells are defined as self-renewing cell populations that can differentiate into multiple distinct cell types. However, hundreds of different human cell lines from embryonic, fetal and adult sources have been called stem cells, even though they range from pluripotent cells-typified by embryonic stem cells, which are capable of virtually unlimited proliferation and differentiation-to adult stem cell lines, which can generate a far more limited repertoire of differentiated cell types. The rapid increase in reports of new sources of stem cells and their anticipated value to regenerative medicine has highlighted the need for a general, reproducible method for classification of these cells. We report here the creation and analysis of a database of global gene expression profiles (which we call the 'stem cell matrix') that enables the classification of cultured human stem cells in the context of a wide variety of pluripotent, multipotent and differentiated cell types. Using an unsupervised clustering method to categorize a collection of approximately 150 cell samples, we discovered that pluripotent stem cell lines group together, whereas other cell types, including brain-derived neural stem cell lines, are very diverse. Using further bioinformatic analysis we uncovered a protein-protein network (PluriNet) that is shared by the pluripotent cells (embryonic stem cells, embryonal carcinomas and induced pluripotent cells). Analysis of published data showed that the PluriNet seems to be a common characteristic of pluripotent cells, including mouse embryonic stem and induced pluripotent cells and human oocytes. Our results offer a new strategy for classifying stem cells and support the idea that pluripotency and self-renewal are under tight control by specific molecular networks.