INCIDENCE MATRIX APPROACH FOR CALCULATING READINESS LEVELS

Contemporary system maturity assessment approaches have failed to provide robust quantitative system evaluations resulting in increased program costs and developmental risks.Standard assessment metrics,such as Technology Readiness Levels（TRL）,do not sufficiently evaluate increasingly complex systems.The System Readiness Level（SRL）is a newly developed system development metric that is a mathematical function of TRL and Integration Readiness Level（IRL） values for the components and connections of a particular system.SRL acceptance has been hindered because of concerns over SRL mathematical operations that may lead to inaccurate system readiness assessments.These inaccurate system readiness assessments are called readiness reversals.A new SRL calculation method using incidence matrices is proposed to alleviate these mathematical concerns.The presence of SRL readiness reversal is modeled for four SRL calculation methods across several system configurations.Logistic regression analysis demonstrates that the proposed Incidence Matrix SRL（IMSRL）method has a decreased presence of readiness reversal than other approaches suggested in the literature.Viable SRL methods will foster greater SRL adoption by systems engineering professionals and will support system development risk reduction goals.     

TNF-induced necroptosis and PARP-1-mediated necrosis represent distinct routes to programmed necrotic cell death

Programmed necrosis is important in many (patho)physiological settings. For specific therapeutic intervention, however, a better knowledge is required whether necrosis occurs through one single “core program” or through several independent pathways. Previously, the poly(ADP-ribose) polymerase (PARP) pathway has been suggested as a crucial element of tumor necrosis factor (TNF)-mediated necroptosis. Here, we show that TNF-induced necroptosis and the PARP pathway represent distinct and independent routes to programmed necrosis. First, DNA-alkylating agents such as 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) or methyl methanesulfonate rapidly activate the PARP pathway, whereas this is a late and secondary event in TNF-induced necroptosis. Second, inhibition of the PARP pathway does not protect against TNF-induced necroptosis, e.g., the PARP-1 inhibitor 3-AB prevented MNNG- but not TNF-induced adenosine-5′-triposphate depletion, translocation of apoptosis-inducing factor, and necrosis. Likewise, olaparib, a more potent and selective PARP-1 inhibitor failed to block TNF-induced necroptosis, identical to knockdown/knockout of PARP-1, pharmacologic and genetic interference with c-Jun N-terminal kinases and calpain/cathepsin proteases as further components of the PARP pathway. Third, interruption of TNF-induced necroptosis by interference with ceramide generation, RIP1 or RIP3 function or by the radical scavenger butylated hydroxyanisole did not prevent programmed necrosis through the PARP pathway. In summary, our results suggest that the currently established role of the PARP pathway in TNF-induced necroptosis needs to be revised, with consequences for the design of future therapeutic strategies.     

Remodeling and dedifferentiation of adult cardiomyocytes during disease and regeneration

Cardiomyocytes continuously generate the contractile force to circulate blood through the body. Imbalances in contractile performance or energy supply cause adaptive responses of the heart resulting in adverse rearrangement of regular structures, which in turn might lead to heart failure. At the cellular level, cardiomyocyte remodeling includes (1) restructuring of the contractile apparatus; (2) rearrangement of the cytoskeleton; and (3) changes in energy metabolism. Dedifferentiation represents a key feature of cardiomyocyte remodeling. It is characterized by reciprocal changes in the expression pattern of “mature” and “immature” cardiomyocyte-specific genes. Dedifferentiation may enable cardiomyocytes to cope with hypoxic stress by disassembly of the energy demanding contractile machinery and by reduction of the cellular energy demand. Dedifferentiation during myocardial repair might provide cardiomyocytes with additional plasticity, enabling survival under hypoxic conditions and increasing the propensity to enter the cell cycle. Although dedifferentiation of cardiomyocytes has been described during tissue regeneration in zebrafish and newts, little is known about corresponding mechanisms and regulatory circuits in mammals. The recent finding that the cytokine oncostatin M (OSM) is pivotal for cardiomyocyte dedifferentiation and exerts strong protective effects during myocardial infarction highlights the role of cytokines as potent stimulators of cardiac remodeling. Here, we summarize the current knowledge about transient dedifferentiation of cardiomyocytes in the context of myocardial remodeling, and propose a model for the role of OSM in this process.     

A place for pragmatism in the dynamics of reason?

In Dynamics of Reason Michael Friedman proposes a kind of synthesis between the neokantianism of Ernst Cassirer, the logical empiricism of Rudolf Carnap, and the historicism of Thomas Kuhn. Cassirer and Carnap are to take care of the Kantian legacy of modern philosophy of science, encapsulated in the concept of the relativized a priori and the globally rational or continuous evolution of scientific knowledge, while Kuhn’s role is to ensure that the historicist character of scientific knowledge is taken seriously. More precisely, Carnapian linguistic frameworks, guarantee that the evolution of science proceeds in a rational manner locally, while Cassirer’s concept of an internally defined conceptual convergence of empirical theories provides the means to maintain the global continuity of scientific reason. In this paper it is argued that Friedman’s Neokantian account of scientific reason based on the concept of the relativized a priori underestimates the pragmatic aspects of the dynamics of scientific reason. To overcome this shortcoming, I propose to reconsider C.I. Lewis’s account of a pragmatic priori, recently modernized and elaborated by Hasok Chang. This may be considered as a first step to a dynamics of an embodied reason, less theoretical and more concrete than Friedman’s Neokantian proposal.     

Winter site fidelity and body condition of three riparian songbird species following a fire

The effects of fire on nonbreeding songbird species in riparian habitat have not been studied. We compared body condition, within-year site fidelity, and between-year site fidelity of 3 songbird species ( Passerella iliaca , Fox Sparrow; Catharus guttatus , Hermit Thrush; and Regulus calendula , Ruby-crowned Kinglet) at 2 coastal riparian sites. Wildfire, which is rare in this habitat, had occurred at 1 of the sites before data collection. A significantly larger proportion of Passerella iliaca was recaptured in subsequent winters at the unburned site than at the burned site, but little difference was found between sites for Catharus guttatus or Regulus calendula . Body mass of all 3 species declined during winter at the burned site, but differences between sites were not significant. Similarly, body mass indices of new captures were lower at the burned site than the unburned site for all 3 species, but these differences were not significant. The within-year recapture rate for all 3 species combined declined at the burned site over the course of the study, possibly due to changes in vegetation structure caused by the fire. Overall, our data suggest that wintering songbirds were resilient to this disturbance, but that response to the post-fire environment differed among foraging guilds. Well-replicated studies that include pre-burn data are needed to evaluate the effects of this disturbance in riparian systems.     

Taphonomy and significance of Jefferson's ground sloth (Xenarthra: Megalonychidae) from Utah

While a variety of mammalian megafauna have been recovered from sediments associated with Lake Bonneville, Utah, sloths have been notably rare. Three species of ground sloth, Megalonyx jeffersonii, Paramylodon harlani, and Nothrotheriops shastensis , are known from the western United States during the Pleistocene. Yet all 3 are rare in the Great Basin, and the few existing records are from localities on the basin margin. The recent discovery of a partial skeleton of Megalonyx jeffersonii at Point-of-the-Mountain, Salt Lake County, Utah, fits this pattern and adds to our understanding of the distribution and ecology of this extinct species. Its occurrence in Lake Bonneville shoreline deposits permits a reasonable age determination of between 22 and 13 ka.