Causal-consistent rollback in a tuple-based language

Rollback is a fundamental technique for ensuring reliability of systems, allowing one, in case of troubles, to recover a past system state. However, the definition of rollback in a concurrent/distributed scenario is quite tricky. We propose an approach based on the notion of causal-consistent reversibility: any given past action can be undone, provided that all the actions caused by it are undone as well. Given that, we define a rollback as the minimal causal-consistent sequence of backward steps able to undo a given action. We define the semantics of such a rollback operator, and show that it satisfies the above specification. The approach that we present is quite general, but we instantiate it in the case of muKlaim, a formal coordination language based on distributed tuple spaces. We remark that this is the first definition of causal-consistent rollback in a shared–memory setting. We illustrate the use of rollback in muKlaim on a simple, but realistic, application scenario

Causal-Consistent Reversibility in a Tuple-Based Language

Causal-consistent reversibility is a natural way of undoing concurrent computations. We study causal-consistent reversibility in the context of µKlaim, a formal coordination language based on distributed tuple spaces. We consider both uncontrolled reversibility, suitable to study the basic properties of the reversibility mechanism, and controlled reversibility based on a rollback operator, more suitable for programming applications. The causality structure of the language, and thus the definition of its reversible semantics, differs from all the reversible languages in the literature because of its generative communication paradigm. In particular, the reversible behavior of µKlaim read primitive, reading a tuple without consuming it, cannot be matched using channel-based communication. We illustrate the reversible extensions of µKlaim on a simple, but realistic, application scenario

Aquafaba de garbanzos: desde las redes sociales a la Industria

La aquafaba es el líquido de cobertura de los garbanzos enlatados. El uso de la aquafaba como espumante y emulsificante se difundió muy rápidamente por internet en la comunidad vegana para la elaboración de mayonesas, helados, merengues, cremas batidas, etc. En general, estas publicaciones no provienen de científicos especializados sino del saber popular. Los porotos de garbanzos son ricos en proteínas y saponinas. Las saponinas son compuestos que se encuentran naturalmente en las células de las legumbres y tradicionalmente, fueron consideradas como factores antinutricionales, y se sugirió removerlas, principalmente por su actividad hemolítica y su característico gusto amargo. Sin embargo, las saponinas son verdaderos detergentes que le imparten un gran poder espumante. En la UNLu estamos estudiando la factibilidad de formular helados sin gluten utilizando como ingrediente a la aquafaba de garbanzos. Hay muy pocos estudios sistemáticos sobre la estabilidad y optimización de las espumas de aquafaba y de nuestro conocimiento, no hay desarrollo de productos industriales. Este proyecto permitirá un aprovechamiento racional de las potencialidades del aquafaba y la mejora de la calidad tecnológica y nutricional de helados destinados tanto a la población vegana como a las personas alérgicas a las proteínas del huevo, leche o trigo

TAMEP are brain tumor parenchymal cells controlling neoplastic angiogenesis and progression

Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor parenchymal cells may promote specific phases of disease progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Notably, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell population, by conditional Sox2-knockout, drastically reduced glioblastoma vascularization and size. Hence, TAMEP emerge as a tumor parenchymal component with a strong impact on glioblastoma progression

A Modified RMCE-Compatible Rosa26 Locus for the Expression of Transgenes from Exogenous Promoters

Generation of gain-of-function transgenic mice by targeting the Rosa26 locus has been established as an alternative to classical transgenic mice produced by pronuclear microinjection. However, targeting transgenes to the endogenous Rosa26 promoter results in moderate ubiquitous expression and is not suitable for high expression levels. Therefore, we now generated a modified Rosa26 (modRosa26) locus that combines efficient targeted transgenesis using recombinase-mediated cassette exchange (RMCE) by Flipase (Flp-RMCE) or Cre recombinase (Cre-RMCE) with transgene expression from exogenous promoters. We silenced the endogenous Rosa26 promoter and characterized several ubiquitous (pCAG, EF1α and CMV) and tissue-specific (VeCad, αSMA) promoters in the modRosa26 locus in vivo. We demonstrate that the ubiquitous pCAG promoter in the modRosa26 locus now offers high transgene expression. While tissue-specific promoters were all active in their cognate tissues they additionally led to rare ectopic expression. To achieve high expression levels in a tissue-specific manner, we therefore combined Flp-RMCE for rapid ES cell targeting, the pCAG promoter for high transgene levels and Cre/LoxP conditional transgene activation using well-characterized Cre lines. Using this approach we generated a Cre/LoxP-inducible reporter mouse line with high EGFP expression levels that enables cell tracing in live cells. A second reporter line expressing luciferase permits efficient monitoring of Cre activity in live animals. Thus, targeting the modRosa26 locus by RMCE minimizes the effort required to target ES cells and generates a tool for the use exogenous promoters in combination with single-copy transgenes for predictable expression in mice

Genetic Inactivation of <i>Notch1</i> Synergizes with Loss of <i>Trp53</i> to Induce Tumor Formation in the Adult Mouse Forebrain

Simultaneous genetic inactivation of the key Notch signaling mediator RBP-Jk and p53 leads to the formation of forebrain tumors in mice, suggesting a tumor suppressor role of the Notch pathway in this context. However, the contribution of individual Notch receptors to the tumor-suppressive activity of Notch signaling in the brain remains elusive. Here, we show that simultaneous Notch1 and Notch2 deletion, similar to complete ablation of canonical Notch signaling by Rbpj inactivation, cooperates with Trp53 deletion to promote tumor growth in the adult forebrain. We also demonstrate that inactivation of Notch1 and Trp53 in cells with active Notch signaling is sufficient to induce brain tumor or hyperplasia formation. Analysis of tumor location suggests a multifocal origin and shows that ventral forebrain regions and olfactory bulbs are the most affected sites. Hence, Notch1 cooperates with p53 to repress malignant transformation in the adult mouse forebrain

Notching up neural stem cell homogeneity in homeostasis and disease

Adult neural stem cells (NSCs) are perceived as a homogeneous population of cells that divide infrequently and are capable of multi-lineage differentiation. However, recent data revealed that independent stem cell lineages act in parallel to maintain neurogenesis and provide a cellular source for tissue repair. In addition, even within the same lineage, the stem and progenitor cells are strikingly heterogeneous including NSCs that are dormant or mitotically active. We will discuss these different NSC populations and activity states with relation to their role in neurogenesis and regeneration but also how these different stem cells respond to aging. NSCs depend on Notch signaling for their maintenance. While Notch-dependence is a common feature among NSC populations, we will discuss how differences in Notch signaling might contribute to adult NSC heterogeneity. Understanding the fate of multiple NSC populations with distinct functions has implications for the mechanisms of aging and regeneration

CaReDeb

Reversible debugging provides developers with a way to execute their applications both forward and backward, seeking the cause of an unexpected or undesired event. In a concurrent setting, reversing actions in the exact reverse order they have been executed may lead to undo many actions that were not related to the bug under analysis. On the other hand, undoing actions in some order that violates causal dependencies may lead to states that could not be reached in a forward execution. We propose an approach based on causal-consistent reversibility: each action can be reversed if all its consequences have already been reversed. The main feature of the approach is that it allows the programmer to easily individuate and undo exactly the actions that caused a given misbehavior till the corresponding bug is reached. This paper major contribution is the individuation of the appropriate primitives for causal-consistent reversible debugging and their prototype implementation in the CaReDeb tool. We also show how to apply CaReDeb to individuate common real-world concurrent bugs