Poincaré on Generalizations and Facts: Construction or Translation?

Much of the focus on Poincaré’s philosophy of science has been on the notion of convention, a crucial concept that has become distinctive of his position. However, other notions have received much less attention. That is the case of verifiable hypotheses. This kind of hypotheses seems to be constituted from the generalization of several observable facts. So, in order to understand what these hypotheses are, we need to know what a fact to Poincaré is. He divides facts into brute and scientific facts. The characterization of this duality is not trivial at all, and leads us to the following questions that we will discuss in this paper: (1) which the part of construction that exists in a scientific fact and which the part of translation, that is, what remains from the brute fact in the scientific one?; and (2) when we conceive a generalized hypothesis, are we supposed to do it from scientific or from brute facts? The clarification of these questions could lead to distinguish the part of construction and the part of translation in the first steps of science, which is essential to get a better understanding of Poincaré’s conception of science.     

Is Leibnizian Calculus Embeddable in First Order Logic?

To explore the extent of embeddability of Leibnizian infinitesimal calculus in first-order logic (FOL) and modern frameworks, we propose to set aside ontological issues and focus on procedural questions. This would enable an account of Leibnizian procedures in a framework limited to FOL with a small number of additional ingredients such as the relation of infinite proximity. If, as we argue here, first order logic is indeed suitable for developing modern proxies for the inferential moves found in Leibnizian infinitesimal calculus, then modern infinitesimal frameworks are more appropriate to interpreting Leibnizian infinitesimal calculus than modern Weierstrassian ones.     

Colon cancer cell-derived 12(S)-HETE induces the retraction of cancer-associated fibroblast via MLC2, RHO/ROCK and Ca<Superscript>2+</Superscript> signalling

Retraction of mesenchymal stromal cells supports the invasion of colorectal cancer cells (CRC) into the adjacent compartment. CRC-secreted 12(S)-HETE enhances the retraction of cancer-associated fibroblasts (CAFs) and therefore, 12(S)-HETE may enforce invasivity of CRC. Understanding the mechanisms of metastatic CRC is crucial for successful intervention. Therefore, we studied pro-invasive contributions of stromal cells in physiologically relevant three-dimensional in vitro assays consisting of CRC spheroids, CAFs, extracellular matrix and endothelial cells, as well as in reductionist models. In order to elucidate how CAFs support CRC invasion, tumour spheroid-induced CAF retraction and free intracellular Ca²⁺ levels were measured and pharmacological- or siRNA-based inhibition of selected signalling cascades was performed. CRC spheroids caused the retraction of CAFs, generating entry gates in the adjacent surrogate stroma. The responsible trigger factor 12(S)-HETE provoked a signal, which was transduced by PLC, IP3, free intracellular Ca²⁺, Ca²⁺-calmodulin-kinase-II, RHO/ROCK and MYLK which led to the activation of myosin light chain 2, and subsequent CAF mobility. RHO activity was observed downstream as well as upstream of Ca²⁺ release. Thus, Ca²⁺ signalling served as central signal amplifier. Treatment with the FDA-approved drugs carbamazepine, cinnarizine, nifedipine and bepridil HCl, which reportedly interfere with cellular calcium availability, inhibited CAF-retraction. The elucidation of signalling pathways and identification of approved inhibitory drugs warrant development of intervention strategies targeting tumour–stroma interaction.     

Are You Receiving Me? A Viable System Model (VSM) Analysis of Purchasing Coordination in a Firm Engaged in Offshoring of Manufacturing Activities

This paper presents an account of the coordination of purchasing activities in a firm that offshored their manufacturing operations that later turned problematic. Empirical data is drawn from a single in-depth case study within a large multinational company which was involved in production offshoring in 2009. The paper draws on the viable systems model (VSM) as the main theoretical lens. First, our findings suggest that purchasing coordination is a loose construct; one in which the role and types of information aggregation in the purchasing process is loosely defined compared to the aggregation of volumes and the effectiveness of sourcing teams. This finding partly explains why many cross-functional sourcing problems occur. Second, that organizational and functional contextual differences can no longer be sidelined in discussions of purchasing coordination because they define how the system’s functions interface and therefore are one of the most essential considerations for better purchasing coordination and ultimately organizational viability.

     

Early microbiota,antibiotics and health

The colonization of the neonatal digestive tract provides a microbial stimulus required for an adequate maturation towards the physiological homeostasis of the host. This colonization, which is affected by several factors, begins with facultative anaerobes and continues with anaerobic genera. Accumulating evidence underlines the key role of the early neonatal period for this microbiota-induced maturation, being a key determinant factor for later health. Therefore, understanding the factors that determine the establishment of the microbiota in the infant is of critical importance. Exposure to antibiotics, either prenatally or postnatally, is common in early life mainly due to the use of intrapartum prophylaxis or to the administration of antibiotics in C-section deliveries. However, we are still far from understanding the impact of early antibiotics and their long-term effects. Increased risk of non-communicable diseases, such as allergies or obesity, has been observed in individuals exposed to antibiotics during early infancy. Moreover, the impact of antibiotics on the establishment of the infant gut resistome, and on the role of the microbiota as a reservoir of resistance genes, should be evaluated in the context of the problems associated with the increasing number of antibiotic resistant pathogenic strains. In this article, we review and discuss the above-mentioned issues with the aim of encouraging debate on the actions needed for understanding the impact of early life antibiotics upon human microbiota and health and for developing strategies aimed at minimizing this impact.     

一种提高视频车速检测精度的方法

通过对基于虚拟线的机动车视频测速方法的精度分析,提出了一种提高测速精度的方法.该方法在车道上定义一个矩形检测区,该检测区在视频图像上呈现出梯形,采用二维图像标定方法将梯形图像区域中任意一点的图像坐标准确地映射为检测区内对应点的地面坐标.通过在车辆经过检测区的视频图像中选取适当的图像帧,可以获得车辆的位移及对应的时间间隔,从而获得较高精度的速度测量结果.     

Translating cancer research into targeted therapeutics

The emphasis in cancer drug development has shifted from cytotoxic, non-specific chemotherapies to molecularly targeted, rationally designed drugs promising greater efficacy and less side effects. Nevertheless, despite some successes drug development remains painfully slow. Here, we highlight the issues involved and suggest ways in which this process can be improved and expedited. We envision an increasing shift to integrated cancer research and biomarker-driven adaptive and hypothesis testing clinical trials. The goal is the development of specific cancer medicines to treat the individual patient, with treatment selection being driven by a detailed understanding of the genetics and biology of the patient and their cancer.     

Pericytes regulate the blood-brain barrier

The blood-brain barrier (BBB) consists of specific physical barriers, enzymes and transporters, which together maintain the necessary extracellular environment of the central nervous system (CNS). The main physical barrier is found in the CNS endothelial cell, and depends on continuous complexes of tight junctions combined with reduced vesicular transport. Other possible constituents of the BBB include extracellular matrix, astrocytes and pericytes, but the relative contribution of these different components to the BBB remains largely unknown. Here we demonstrate a direct role of pericytes at the BBB in vivo. Using a set of adult viable pericyte-deficient mouse mutants we show that pericyte deficiency increases the permeability of the BBB to water and a range of low-molecular-mass and high-molecular-mass tracers. The increased permeability occurs by endothelial transcytosis, a process that is rapidly arrested by the drug imatinib. Furthermore, we show that pericytes function at the BBB in at least two ways: by regulating BBB-specific gene expression patterns in endothelial cells, and by inducing polarization of astrocyte end-feet surrounding CNS blood vessels. Our results indicate a novel and critical role for pericytes in the integration of endothelial and astrocyte functions at the neurovascular unit, and in the regulation of the BBB.     

绿片岩的单轴压缩各向异性蠕变试验研究

通过对锦屏二级水电站辅助交通洞的绿片岩单轴压缩蠕变特性试验,研究了轴向荷载方向与层理之间的不同关系对瞬时应变、应力应变关系、轴向应变速率、衰减蠕变持续时间和蠕变破坏机理的影响.研究结果表明:在相同低应力水平下,垂直于层理时的瞬时应变增量大于平行于层理时的瞬时应变增量,而在相同较高应力水平下垂直于层理时的瞬时应变增量小于平行于层理时的瞬时应变增量;同等应力水平条件下,垂直于层理时的轴向应变速率和衰减蠕变持续时间均小于平行于层理时的轴向应变速率和衰减蠕变持续时间.同时,当轴向荷载垂直或者平行于层理时,应力应变关系曲线均出现了压密、弹性变形、裂纹扩展和峰后破坏阶段,且蠕变破坏类型均属于脆性破坏.