The size and scope of microarray experiments continue to increase. However, datasets generated on different platforms or at different centres contain biases. Improved techniques are needed to remove platform- and batch-specific biases. One experimental control is the replicate hybridization of a subset of samples at each site or on each platform to learn the relationship between the two platforms. To date, no algorithm exists to specifically use this type of control. LTR is a linear-modelling-based algorithm that learns the relationship between different microarray batches from replicate hybridizations. LTR was tested on a new benchmark dataset of 20 samples hybridized to different Affymetrix microarray platforms. Before LTR, the two platforms were significantly different; application of LTR removed this bias. LTR was tested with six separate data pre-processing algorithms, and its effectiveness was independent of the pre-processing algorithm. Sample-size experiments indicate that just three replicate hybridizations can significantly reduce bias. An R library implementing LTR is available.

If the condition of the Blackfeet Indians at this time is to be taken as an index of the character of trusteeship which the Government imposes upon other Indians, the w d has been a failure. The spectacle is a depressing one and calls not only for immediate relief but for an entire and permanent change in the manner of handling their affairs. --Senator Harry Lane, 1914 Give us a fair and new deal as we know ourselves the old system is no success. -Blackfeet Councilman Rides at the Door, 1933 INTRODUCTION The Indian Reorganization Act (IRA), the cornerstone of the Indian New Deal, is the most important piece of legislation in twentieth-century American Indian policy-making. Earl Old Person, the great full-blooded Blackfeet leader, discussed the IRA’S role in twentieth-century Indian progress in his speech to the 1966 convention of the National Congress of American Indians. “The first breakthrough came with the Indian Reorganization Act of 1934. This permitted a Government policy of organization by allowing tribes to adopt constitutions which provided terms for managing their own affairs.”’ The IRA represented the start of a long-sought and much-needed dialogue between Indian leaders and federal officials, whose organizing principle under Commissioner of Indian Affairs John Collier rested on “the revolutionary proposition that Indians were not obstacles, but peoples.” The IRA became an attenuated version of Collier’s vision of Native political economy- a syncretic economy managed by empowered tribal governments that would adopt white business practices and, Collier hoped, encourage a renewal of Indian culture.

Unlabelled

Hidden Markov models (HMMs) are probabilistic models that are well-suited to solve many different classification problems in computation biology. StochHMM provides a command-line program and C++ library that can implement a traditional HMM from a simple text file. StochHMM provides researchers the flexibility to create higher-order emissions, integrate additional data sources and/or user-defined functions into multiple points within the HMM framework. Additional features include user-defined alphabets, ability to handle ambiguous characters in an emission-dependent manner, user-defined weighting of state paths and ability to tie transition probabilities to sequence.

Availability and implementation

StochHMM is implemented in C++ and is available under the MIT License. Software, source code, documentation and examples can be found at http://github.com/KorfLab/StochHMM.

Controlled immune responses to infection and injury involve complex molecular signalling networks with coordinated and often opposing actions. Eicosanoids and related bioactive lipid mediators derived from polyunsaturated fatty acids constitute a major bioactive lipid network that is among the most complex and challenging pathways to map in a physiological context. Eicosanoid signalling, similar to cytokine signalling and inflammasome formation, has primarily been viewed as a pro-inflammatory component of the innate immune response; however, recent advances in lipidomics have helped to elucidate unique eicosanoids and related docosanoids with anti-inflammatory and pro-resolution functions. This has advanced our overall understanding of the inflammatory response and its therapeutic implications. The induction of a pro-inflammatory and anti-inflammatory eicosanoid storm through the activation of inflammatory receptors by infectious agents is reviewed here.

Dietary fish oil containing ω3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), elicit cardioprotective and anti-inflammatory effects through unresolved mechanisms that may involve competition and inhibition at multiple levels. Here, we report the effects of arachidonic acid (AA), EPA, and DHA supplementation on membrane incorporation, phospholipase A(2) catalyzed release, and eicosanoid production in RAW264.7 macrophages. Using a targeted lipidomics approach, we observed that Toll-like receptor 4 and purinergic receptor activation of supplemented cells leads to the release of 22-carbon fatty acids that potently inhibit cyclooxygenase pathways. This inhibition was able to shunt metabolism of AA to lipoxygenase pathways, augmenting leukotriene and other lipoxygenase mediator synthesis. In resident peritoneal macrophages, docosapentaenoic acid (DPA) was responsible for cyclooxygenase inhibition after EPA supplementation, offering fresh insights into how EPA exerts anti-inflammatory effects indirectly through elongation to 22-carbon DPA.

It is conceivable that, in the near future, an assay that defines the likelihood of a patient with advanced cancer to respond to immunotherapy based on PD1/L1 blockade will be the initial decision point to select the treatment of patients with any cancer type.