Signs, toy models, and the a priori: from Helmholtz to Wittgenstein

The Marburg neo-Kantians argue that Hermann von Helmholtz’s empiricist account of the a priori does not account for certain knowledge, since it is based on a psychological phenomenon, trust in the regularities of nature. They argue that Helmholtz’s account raises the ‘problem of validity’ (Gültigkeitsproblem): how to establish a warranted claim that observed regularities are based on actual relations. I reconstruct Heinrich Hertz’s and Ludwig Wittgenstein’s Bild theoretic answer to the problem of validity: that scientists and philosophers can depict the necessary a priori constraints on states of affairs in a given system, and can establish whether these relations are actual relations in nature. The analysis of necessity within a system is a lasting contribution of the Bild theory. However, Hertz and Wittgenstein argue that the logical and mathematical sentences of a Bild are rules, tools for constructing relations, and the rules themselves are meaningless outside the theory. Carnap revises the argument for validity by attempting to give semantic rules for translation between frameworks. Russell and Quine object that pragmatics better accounts for the role of a priori reasoning in translating between frameworks. The conclusion of the tale, then, is a partial vindication of Helmholtz’s original account.     

Dynamics of Drosophila embryonic patterning network perturbed in space and time using microfluidics

Biochemical networks are perturbed both by fluctuations in environmental conditions and genetic variation. These perturbations must be compensated for, especially when they occur during embryonic pattern formation. Complex chemical reaction networks displaying spatiotemporal dynamics have been controlled and understood by perturbing their environment in space and time. Here, we apply this approach using microfluidics to investigate the robust network in Drosophila melanogaster that compensates for variation in the Bicoid morphogen gradient. We show that the compensation system can counteract the effects of extremely unnatural environmental conditions--a temperature step--in which the anterior and posterior halves of the embryo are developing at different temperatures and thus at different rates. Embryonic patterning was normal under this condition, suggesting that a simple reciprocal gradient system is not the mechanism of compensation. Time-specific reversals of the temperature step narrowed down the critical period for compensation to between 65 and 100 min after onset of embryonic development. The microfluidic technology used here may prove useful to future studies, as it allows spatial and temporal regulation of embryonic development.     

Negation scope detection with a conditional random field model

Identifying negation cues and their scope in a text is an important subtask of information extrac-tion that can benefit other natural language processing tasks, including but not limited to medical da-ta mining, relation extraction, question answering and sentiment analysis.The tasks of negation cue and negation scope detection can be treated as sequence labelling problems.In this paper, a system is presented having two components: negation cue detection and negation scope detection.In the first phase, a conditional random field ( CRF) model is trained to detect the negation cues using a lexicon of negation words and some lexical and contextual features.Then, another CRF model is trained to detect the scope of each negation cue identified in the first phase, using basic lexical and contextual features.These two models are trained and tested using the dataset distributed within the*Sem Shared Task 2012 on resolving the scope and focus of negation.Experimental results show that the system outperformed all the systems submitted to this shared task.     

Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus

TREX1 acts in concert with the SET complex in granzyme A-mediated apoptosis, and mutations in TREX1 cause Aicardi-Goutières syndrome and familial chilblain lupus. Here, we report monoallelic frameshift or missense mutations and one 3' UTR variant of TREX1 present in 9/417 individuals with systemic lupus erythematosus but absent in 1,712 controls (P = 4.1 x 10(-7)). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE.     

The impact of economic growth in mortality modelling for selected OECD countries

The health of a population is affected by social, environmental, and economic factors. Pension providers and consultants, insurance companies, government agencies and individuals in the developed world have a vested interest in understanding how the economic growth will impact on the life expectancy of their population. Therefore, changes in death rates may occur due to climate and economic changes. In this study, we extend a previous study into excess deaths as a result of climate change to also provide a comprehensive investigation of the impact of economic changes using annual female and male data for 5 developed OECD countries. We find that there is strong negative relationship between mortality index, and climate and economic proxies. This model shows to provide better fitting and forecasting results both for females and males, and for all countries studied.     

Stochastic models underlying Croston's method for intermittent demand forecasting

Croston's method is widely used to predict inventory demand when it is intermittent. However, it is an ad hoc method with no properly formulated underlying stochastic model. In this paper, we explore possible models underlying Croston's method and three related methods, and we show that any underlying model will be inconsistent with the properties of intermittent demand data. However, we find that the point forecasts and prediction intervals based on such underlying models may still be useful. Copyright © 2005 John Wiley & Sons, Ltd.     

Hypothalamic K(ATP) channels control hepatic glucose production

Obesity is the driving force behind the worldwide increase in the prevalence of type 2 diabetes mellitus. Hyperglycaemia is a hallmark of diabetes and is largely due to increased hepatic gluconeogenesis. The medial hypothalamus is a major integrator of nutritional and hormonal signals, which play pivotal roles not only in the regulation of energy balance but also in the modulation of liver glucose output. Bidirectional changes in hypothalamic insulin signalling therefore result in parallel changes in both energy balance and glucose metabolism. Here we show that activation of ATP-sensitive potassium (K(ATP)) channels in the mediobasal hypothalamus is sufficient to lower blood glucose levels through inhibition of hepatic gluconeogenesis. Finally, the infusion of a K(ATP) blocker within the mediobasal hypothalamus, or the surgical resection of the hepatic branch of the vagus nerve, negates the effects of central insulin and halves the effects of systemic insulin on hepatic glucose production. Consistent with these results, mice lacking the SUR1 subunit of the K(ATP) channel are resistant to the inhibitory action of insulin on gluconeogenesis. These findings suggest that activation of hypothalamic K(ATP) channels normally restrains hepatic gluconeogenesis, and that any alteration within this central nervous system/liver circuit can contribute to diabetic hyperglycaemia.