Melatonin,clock genes and mitochondria in sepsis

After the characterization of the central pacemaker in the suprachiasmatic nucleus, the expression of clock genes was identified in several peripheral tissues including the immune system. The hierarchical control from the central clock to peripheral clocks extends to other functions including endocrine, metabolic, immune, and mitochondrial responses. Increasing evidence links the disruption of the clock genes expression with multiple diseases and aging. Chronodisruption is associated with alterations of the immune system, immunosenescence, impairment of energy metabolism, and reduction of pineal and extrapineal melatonin production. Regarding sepsis, a condition coursing with an exaggerated response of innate immunity, experimental and clinical data showed an alteration of circadian rhythms that reflects the loss of the normal oscillation of the clock. Moreover, recent data point to that some mediators of the immune system affects the normal function of the clock. Under specific conditions, this control disappears reactivating the immune response. So, it seems that clock gene disruption favors the innate immune response, which in turn induces the expression of proinflammatory mediators, causing a further alteration of the clock. Here, the clock control of the mitochondrial function turns off, leading to a bioenergetic decay and formation of reactive oxygen species that, in turn, activate the inflammasome. This arm of the innate immunity is responsible for the huge increase of interleukin-1β and entrance into a vicious cycle that could lead to the death of the patient. The broken clock is recovered by melatonin administration, that is accompanied by the normalization of the innate immunity and mitochondrial homeostasis. Thus, this review emphasizes the connection between clock genes, innate immunity and mitochondria in health and sepsis, and the role of melatonin to maintain clock homeostasis.     

Gibbs, Einstein and the Foundations of Statistical Mechanics

It is generally accepted that, around the turn of the century, GIBBS and EINSTEIN independently developed two equivalent formulations of statistical mechanics. GIBBS version is taken as genuine and rigorous, while EINSTEINs, despite some features which are characteristic of him, is usually considered a not totally satisfactory attempt. It will be shown in the present work that such a picture is oversimplified and requires further nuancing. In fact, there are significant differences, with important implications which have not been sufficiently examined, between the two formulations. Several issues relating to the impact of the two versions will also be addressed. (Received April 4, 1998)     

协同网络组织——新型商业模式的研究议程

最近涌现出的协同网络组织（CNO）或者称为简单协同网络的概念正在根本性地改变着商业、工业、文化和社会行为的组织形式，它代表着一个动态、多学科的研究和开发领域。本书从包含在协同网络组织中的各个学科里总结出了一些建议，目的在于为悄然兴起的协同网络建立起一系列的研究议程。本书罗列的建议和结论都得自于“THINK创新”计划，该计划涉及到了跨越学术、研究和工业领域250余位专家和预言家。     

计算数学基础：Santander年会2005

本书是2005年6月30日-7月9日在西班牙Santander举行的“计算数学基础”国际会议的论文集。该会议由计算数学基础协会举办。自1995年起每两至三年召开一次，目的是促进计算数学的基础研究，并注意与数学、计算机科学的交叉以及各种新应用。本次会议为第4次，有数百人参加，计有18个大会报告及多个分组会议，[第一段]     

A Systemic Framework to Develop Sustainable Engineering Solutions in Rural Communities in Colombia

In several rural areas in Colombia there is a serious lack of water quality supply. Thereby the problematic situation is understood as complex one that involves stakeholders with pluralistic interests, multiple variables and requires the development of sustainable and suitable solutions. In order to address this issue, this paper proposes an integration of engineering design framework (CDIO) with a systemic approach. Particularly the approach emphasizes on systemic elements such as autonomy, systems within systems, cooperation between stakeholders and cause effect relations; it also proposes a previous observing phase for engineering design framework. Thus the proposed systemic framework aims to generate projects that improve living conditions in rural communities and promote the production of knowledge between the stakeholders to ensure sustainability in the long term. To illustrate the proposal, this work contains a case study that discusses a project carried out by a research team—Ingenieros Sin Fronteras Colombia—in a rural district near to Colombia’s capital. The experience, which involved and benefited 16 families in the community, provided strong evidence to support the proposed framework. The paper concludes with a discussion about the replication of this proposal in other contexts.     

Testing and forecasting the degree of integration in the US inflation rate

In this article we model the log of the US inflation rate by means of fractionally integrated processes. We use the tests of Robinson (1994) for testing this type of hypothesis, which include, as particular cases, the I(0) and I(1) specifications, and which also, unusually, have standard null and local limit distributions. A model selection criterion is established to determine which may be the best model specification of the series, and the forecasting properties of the selected models are also examined. The results vary substantially depending on how we specify the disturbances. Thus, if they are white noise, the series is I(d) with d fluctuating around 0.25; however, imposing autoregressive disturbances, the log of the US inflation rate seems to be anti‐persistent, with an order of integration smaller than zero. Looking at the forecasting properties, those models based on autocorrelated disturbances (with d < 0) predict better over a short horizon, while those based on white noise disturbances (with d > 0) seem to predict better over longer periods of time. Copyright © 2005 John Wiley & Sons, Ltd.     

Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation

Excessive inflammation and tumour-necrosis factor (TNF) synthesis cause morbidity and mortality in diverse human diseases including endotoxaemia, sepsis, rheumatoid arthritis and inflammatory bowel disease. Highly conserved, endogenous mechanisms normally regulate the magnitude of innate immune responses and prevent excessive inflammation. The nervous system, through the vagus nerve, can inhibit significantly and rapidly the release of macrophage TNF, and attenuate systemic inflammatory responses. This physiological mechanism, termed the 'cholinergic anti-inflammatory pathway' has major implications in immunology and in therapeutics; however, the identity of the essential macrophage acetylcholine-mediated (cholinergic) receptor that responds to vagus nerve signals was previously unknown. Here we report that the nicotinic acetylcholine receptor alpha7 subunit is required for acetylcholine inhibition of macrophage TNF release. Electrical stimulation of the vagus nerve inhibits TNF synthesis in wild-type mice, but fails to inhibit TNF synthesis in alpha7-deficient mice. Thus, the nicotinic acetylcholine receptor alpha7 subunit is essential for inhibiting cytokine synthesis by the cholinergic anti-inflammatory pathway.