Proliferation versus Differentiation: Redefining Retinoic Acids Role.

Retinoic acid is commonly used in culture to differentiate stem cells into neurons and has established neural differentiation functions in vivo in developing and adult organisms. In this issue of Stem Cell Reports, Mishra et al. (2018) broaden its role in stem cell functions, showing that retinoic acid is necessary for stem and progenitor cell proliferation in the adult brain

Biophysical regulation of stem cell behavior within the niche.

Stem cells reside within most tissues throughout the lifetimes of mammalian organisms. To maintain their capacities for division and differentiation and thereby build, maintain, and regenerate organ structure and function, these cells require extensive and precise regulation, and a critical facet of this control is the local environment or niche surrounding the cell. It is well known that soluble biochemical signals play important roles within such niches, and a number of biophysical aspects of the microenvironment, including mechanical cues and spatiotemporally varying biochemical signals, have also been increasingly recognized to contribute to the repertoire of stimuli that regulate various stem cells in various tissues of both vertebrates and invertebrates. For example, biochemical factors immobilized to the extracellular matrix or the surface of neighboring cells can be spatially organized in their placement. Furthermore, the extracellular matrix provides mechanical support and regulatory information, such as its elastic modulus and interfacial topography, which modulate key aspects of stem cell behavior. Numerous examples of each of these modes of regulation indicate that biophysical aspects of the niche must be appreciated and studied in conjunction with its biochemical properties

Folk teleology drives persistence judgments

Two separate research programs have revealed two different factors that feature in our judgments of whether some entity persists. One program—inspired by Knobe—has found that normative considerations affect persistence judgments. For instance, people are more inclined to view a thing as persisting when the changes it undergoes lead to improvements. The other program—inspired by Kelemen—has found that teleological considerations affect persistence judgments. For instance, people are more inclined to view a thing as persisting when it preserves its purpose. Our goal in this paper is to determine what causes persistence judgments. Across four studies, we pit normative considerations against teleological considerations. And using causal modeling procedures, we find a consistent, robust pattern with teleological and not normative considerations directly causing persistence judgments. Our findings put teleology in the driver’s seat, while at the same time shedding further light on our folk notion of an object

TaskInsight: Understanding Task Schedules Effects on Memory and Performance

Recent scheduling heuristics for task-based applications have managed to improve their by taking into account memory-related properties such as data locality and cache sharing. However, there is still a general lack of tools that can provide insights into why, and where, different schedulers improve memory behavior, and how this is related to the applications' performance. To address this, we present TaskInsight, a technique to characterize the memory behavior of different task schedulers through the analysis of data reuse between tasks. TaskInsight provides high-level, quantitative information that can be correlated with tasks' performance variation over time to understand data reuse through the caches due to scheduling choices. TaskInsight is useful to diagnose and identify which scheduling decisions affected performance, when were they taken, and why the performance changed, both in single and multi-threaded executions. We demonstrate how TaskInsight can diagnose examples where poor scheduling caused over 10% difference in performance for tasks of the same type, due to changes in the tasks' data reuse through the private and shared caches, in single and multi-threaded executions of the same application. This flexible insight is key for optimization in many contexts, including data locality, throughput, memory footprint or even energy efficiency.We thank the reviewers for their feedback. This work was supported by the Swedish Research Council, the Swedish Foundation for Strategic Research project FFL12-0051 and carried out within the Linnaeus Centre of Excellence UPMARC, Uppsala Programming for Multicore Architectures Research Center. This paper was also published with the support of the HiPEAC network that received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 687698.Peer ReviewedPostprint (published version

The Viability of the Economy of Oromia: A Point of Departure

The Oromo, an oppressed, colonized, ethno-national group within Ethiopia, are engaged in a struggle to achieve full political and economic participation within a national entity. Given an undernourishment rate approaching 50 percent and an agriculture which provides a means of livelihood for 80 percent of the labor force, any future leadership will have to address the interrelated issues of agriculture and economy. An examination of production numbers indicates that an independent Oromia would not be at an agricultural disadvantage when compared with remaining as a participating entity within the present boundaries of Ethiopia. Policies directed toward overcoming undernutrition cannot be formulated apart from understanding the implications of the nature of economic exchange which is assumed to be non-coercive. In the case of food, this thesis argues that the non- coerciveness assumption does not hold, resulting in the lack of market access to food— undernutrition and death—for those lacking adequate monetary or production resources. Two additional constraints that must be taken into account are the lack of price responsiveness in aggregate agriculture which results in long periods of low prices for primary crop products and the fallacy of composition which calls into question the practice of assuming that a development activity that works in one nation will work well if others implement the same development activity. While economic theorists argue that conventional economic theory is an objective, value-free description of a natural human process that is true for all times and all places, there is sufficient basis to argue that conventional economic theory is value-laden and socially constructed in such a manner as to enhance and reinforce the dominant Western set of values and the existing power structures and mechanisms for the distribution of goods and services. If economic systems are socially constructed, then alternative socially constructed systems are possible. This thesis proposes using a dynamic concept of wealth in combination with the culture, values, and traditions of the Oromo as a point of departure for conceptualizing an economic system that may be better suited for establishing a viable economy of Oromia than the conventional model

Spatial and Temporal Cache Sharing Analysis in Tasks

Proceedings of the First PhD Symposium on Sustainable Ultrascale Computing Systems (NESUS PhD 2016) Timisoara, Romania. February 8-11, 2016.Understanding performance of large scale multicore systems is crucial for getting faster execution times and optimize workload efficiency, but it is becoming harder due to the increased complexity of hardware architectures. Cache sharing is a key component for performance in modern architectures, and it has been the focus of performance analysis tools and techniques in recent years. At the same time, new programming models have been introduced to aid the programmer dealing with the complexity of large scale systems, simplifying the coding process and making applications more scalable regardless of resource sharing. Taskbased runtime systems are one example of this that became popular recently. In this work we develop models to tackle performance analysis of shared resources in the task-based context, and for that we study cache sharing both in temporal and spatial ways. In temporal cache sharing, the effect of data reused over time by the tasks executed is modeled to predict different scenarios resulting in a tool called StatTask. In spatial cache sharing, the effect of tasks fighting for the cache at a given point in time through their execution is quantified and used to model their behavior on arbitrary cache sizes. Finally, we explain how these tools set up a unique and solid platform to improve runtime systems schedulers, maximizing performance of execution of large-scale task-based applications.European Cooperation in Science and Technology. COSTThe work presented in this paper has been partially supported by EU under the COST programme Action IC1305,‘Network for Sustainable Ultrascale Computing (NESUS)’, and by the Swedish Research Council, carried out within the Linnaeus centre of excellence UPMARC, Uppsala Programming for Multicore Architectures Research Center

Nox2 redox signaling maintains essential cell populations in the brain.

Reactive oxygen species (ROS) are conventionally classified as toxic consequences of aerobic life, and the brain is particularly susceptible to ROS-induced oxidative stress and damage owing to its high energy and oxygen demands. NADPH oxidases (Nox) are a widespread source of brain ROS implicated in seizures, stroke and neurodegeneration. A physiological role for ROS generation in normal brain function has not been established, despite the fact that mice and humans lacking functional Nox proteins have cognitive deficits. Using molecular imaging with Peroxyfluor-6 (PF6), a new selective fluorescent indicator for hydrogen peroxide (H(2)O(2)), we show that adult hippocampal stem/progenitor cells (AHPs) generate H(2)O(2) through Nox2 to regulate intracellular growth signaling pathways, which in turn maintains their normal proliferation in vitro and in vivo. Our results challenge the traditional view that brain ROS are solely deleterious by demonstrating that controlled ROS chemistry is needed for maintaining specific cell populations