On the Role of the Michelson–Morley Experiment: Einstein in Chicago

This article discusses new material, published in volume 12 of the Collected Papers of Albert Einstein, that addresses Einstein’s knowledge of the Michelson–Morley experiment prior to 1905: in a lecture in Chicago in 1921, Einstein referred to the experiment, mentioned when he came upon it and hinted at its influence. Arguments are presented to explain the contrast with Einstein’s later pronouncements on the role of the experiment.     

Insertional mutagenesis identifies multiple networks of cooperating genes driving intestinal tumorigenesis

The evolution of colorectal cancer suggests the involvement of many genes. To identify new drivers of intestinal cancer, we performed insertional mutagenesis using the Sleeping Beauty transposon system in mice carrying germline or somatic Apc mutations. By analyzing common insertion sites (CISs) isolated from 446 tumors, we identified many hundreds of candidate cancer drivers. Comparison to human data sets suggested that 234 CIS-targeted genes are also dysregulated in human colorectal cancers. In addition, we found 183 CIS-containing genes that are candidate Wnt targets and showed that 20 CISs-containing genes are newly discovered modifiers of canonical Wnt signaling. We also identified mutations associated with a subset of tumors containing an expanded number of Paneth cells, a hallmark of deregulated Wnt signaling, and genes associated with more severe dysplasia included those encoding members of the FGF signaling cascade. Some 70 genes had co-occurrence of CIS pairs, clustering into 38 sub-networks that may regulate tumor development.     

MICALs in control of the cytoskeleton,exocytosis, and cell death

MICALs form an evolutionary conserved family of multidomain signal transduction proteins characterized by a flavoprotein monooxygenase domain. MICALs are being implicated in the regulation of an increasing number of molecular and cellular processes including cytoskeletal dynamics and intracellular trafficking. Intriguingly, some of these effects are dependent on the MICAL monooxygenase enzyme and redox signaling, while other functions rely on other parts of the MICAL protein. Recent breakthroughs in our understanding of MICAL signaling identify the ability of MICALs to bind and directly modify the actin cytoskeleton, link MICALs to the docking and fusion of exocytotic vesicles, and uncover MICALs as anti-apoptotic proteins. These discoveries could lead to therapeutic advances in neural regeneration, cancer, and other diseases.     

Mutations in the pre-replication complex cause Meier-Gorlin syndrome

Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears1?3. Both pre- and post-natal growth are impaired in this disorder, and although microcephaly is often evident, intellect is usually normal in this syndrome. We report here that individuals with this disorder show marked locus heterogeneity, and we identify mutations in five separate genes: ORC1, ORC4, ORC6, CDT1 and CDC6. All of these genes encode components of the pre-replication complex, implicating defects in replication licensing as the cause of a genetic syndrome with distinct developmental abnormalities.     

Power and Sample Size Computation for Wald Tests in Latent Class Models

Latent class (LC) analysis is used by social, behavioral, and medical science researchers among others as a tool for clustering (or unsupervised classification) with categorical response variables, for analyzing the agreement between multiple raters, for evaluating the sensitivity and specificity of diagnostic tests in the absence of a gold standard, and for modeling heterogeneity in developmental trajectories. Despite the increased popularity of LC analysis, little is known about statistical power and required sample size in LC modeling. This paper shows how to perform power and sample size computations in LC models using Wald tests for the parameters describing association between the categorical latent variable and the response variables. Moreover, the design factors affecting the statistical power of these Wald tests are studied. More specifically, we show how design factors which are specific for LC analysis, such as the number of classes, the class proportions, and the number of response variables, affect the information matrix. The proposed power computation approach is illustrated using realistic scenarios for the design factors. A simulation study conducted to assess the performance of the proposed power analysis procedure shows that it performs well in all situations one may encounter in practice.     

Forms of Causal Explanation

In the literature on scientific explanation two types of pluralism are very common. The first concerns the distinction between explanations of singular facts and explanations of laws: there is a consensus that they have a different structure. The second concerns the distinction between causal explanations and uni.cation explanations: most people agree that both are useful and that their structure is different. In this article we argue for pluralism within the area of causal explanations: we claim that the structure of a causal explanation depends on the causal structure of the relevant fragment of the world and on the interests of the explainer.