Deconstructing and reconstructing the mouse and human early embryo.

The emergence of form and function during mammalian embryogenesis is a complex process that involves multiple regulatory levels. The foundations of the body plan are laid throughout the first days of post-implantation development as embryonic stem cells undergo symmetry breaking and initiate lineage specification, in a process that coincides with a global morphological reorganization of the embryo. Here, we review experimental models and how they have shaped our current understanding of the post-implantation mammalian embryo.European Research Council (669198) Wellcome Trust (098287/Z/12/Z) Early Career Leverhulme Trust fellowship

Cloud engineering is search based software engineering too

Many of the problems posed by the migration of computation to cloud platforms can be formulated and solved using techniques associated with Search Based Software Engineering (SBSE). Much of cloud software engineering involves problems of optimisation: performance, allocation, assignment and the dynamic balancing of resources to achieve pragmatic trade-offs between many competing technical and business objectives. SBSE is concerned with the application of computational search and optimisation to solve precisely these kinds of software engineering challenges. Interest in both cloud computing and SBSE has grown rapidly in the past five years, yet there has been little work on SBSE as a means of addressing cloud computing challenges. Like many computationally demanding activities, SBSE has the potential to benefit from the cloud; ‘SBSE in the cloud’. However, this paper focuses, instead, of the ways in which SBSE can benefit cloud computing. It thus develops the theme of ‘SBSE for the cloud’, formulating cloud computing challenges in ways that can be addressed using SBSE

50 years of isolation

The traditional means for isolating applications from each other is via the use of operating system provided “process” abstraction facilities. However, as applications now consist of multiple fine-grained components, the traditional process abstraction model is proving to be insufficient in ensuring this isolation. Statistics indicate that a high percentage of software failure occurs due to propagation of component failures. These observations are further bolstered by the attempts by modern Internet browser application developers, for example, to adopt multi-process architectures in order to increase robustness. Therefore, a fresh look at the available options for isolating program components is necessary and this paper provides an overview of previous and current research on the area

Self-organization of stem cells into embryos: A window on early mammalian development.

Embryonic development is orchestrated by robust and complex regulatory mechanisms acting at different scales of organization. In vivo studies are particularly challenging for mammals after implantation, owing to the small size and inaccessibility of the embryo. The generation of stem cell models of the embryo represents a powerful system with which to dissect this complexity. Control of geometry, modulation of the physical environment, and priming with chemical signals reveal the intrinsic capacity of embryonic stem cells to make patterns. Adding the stem cells for the extraembryonic lineages generates three-dimensional models that are more autonomous from the environment and recapitulate many features of the pre- and postimplantation mouse embryo, including gastrulation. Here, we review the principles of self-organization and how they set cells in motion to create an embryo.M.N.S received funding from an Early Career Leverhulme Trust fellowship and an Advanced EMBO fellowship. Work in the laboratory of M.Z-G. is funded by the Wellcome Trust (207415/Z/17/Z) and the European Research Council (ERC grant 669198). Work of E.D.S. is funded by NIH grant GM101653

LibrettOS: A Dynamically Adaptable Multiserver-Library OS

We present LibrettOS, an OS design that fuses two paradigms to simultaneously address issues of isolation, performance, compatibility, failure recoverability, and run-time upgrades. LibrettOS acts as a microkernel OS that runs servers in an isolated manner. LibrettOS can also act as a library OS when, for better performance, selected applications are granted exclusive access to virtual hardware resources such as storage and networking. Furthermore, applications can switch between the two OS modes with no interruption at run-time. LibrettOS has a uniquely distinguishing advantage in that, the two paradigms seamlessly coexist in the same OS, enabling users to simultaneously exploit their respective strengths (i.e., greater isolation, high performance). Systems code, such as device drivers, network stacks, and file systems remain identical in the two modes, enabling dynamic mode switching and reducing development and maintenance costs. To illustrate these design principles, we implemented a prototype of LibrettOS using rump kernels, allowing us to reuse existent, hardened NetBSD device drivers and a large ecosystem of POSIX/BSD-compatible applications. We use hardware (VM) virtualization to strongly isolate different rump kernel instances from each other. Because the original rumprun unikernel targeted a much simpler model for uniprocessor systems, we redesigned it to support multicore systems. Unlike kernel-bypass libraries such as DPDK, applications need not be modified to benefit from direct hardware access. LibrettOS also supports indirect access through a network server that we have developed. Applications remain uninterrupted even when network components fail or need to be upgraded. Finally, to efficiently use hardware resources, applications can dynamically switch between the indirect and direct modes based on their I/O load at run-time. [full abstract is in the paper]Comment: 16th ACM SIGPLAN/SIGOPS International Conference on Virtual Execution Environments (VEE '20), March 17, 2020, Lausanne, Switzerlan

Salience is in the eye of the beholder:Increased pupil size reflects acoustically salient variables

‘Salience’ is a term frequently used in linguistics but an exact definition for the concept is lacking. Recent technological advances which allow us to explore the cognitive processing of so-called salient linguistic features could provide us with quantifiable measures of ‘salience’, and lead to a further understanding of the concept and its relationship to language acquisition and change. In this paper we measure pupil dilation with the assumption that auditory salience results in a change in pupil size, as an effect of cognitive load. We report an experimental study observing Dutch participants' pupil sizes when listening to stimuli containing salient and non-salient variants of linguistic variables (e.g. Dutch coda/r/; speech intensity, word frequency). Using Generalized Additive Mixed Modelling (GAMM), we find pupil size increases for three of six stimuli categories. We consider our findings in light of the speech processing literature, address the (dis)advantages of the technique, and formulate some recommendations for future advances in neurophysiological measures in (socio)linguistics

Xenophon and the Tradition on the Strategoi in Fourth-Century Athens

After studying  individual careers and traditions concerning the  most important Athenian strategoi of the Fourth century B.C. (in particular Chabrias, Iphicrates, Timotheus and Chares), the aim of this paper is to offer now an overview of Xenophon’s interpretations. The attitude of the historian, in fact, is very interesting and seems to be included in a general will to minimize the new Athenian hegemony and to ascribe its successes to the Spartan crisis, omitting or only mentioning some of the main political and military events of the Athenian history in these years and often obliterating its prominent personalities. However, even though Xenophon shows little interest in Conon, Callistratus or Chabrias (whose enterprises are systematically neglected), we can detect a more positive attention to Timotheus and even to Chares (usually so disparaged), till the amazing involvement in Iphicrates’ personality, about whom Xenophontic praises are famous. In this paper, therefore, we will analyze if and to what extent Xenophon contributes to a correct reconstruction of the activities of these strategoi, by comparison with other surviving traditions and trying to understand his different attitudes.Dopo lo studio delle singole carriere e tradizioni riguardanti i più grandi strateghi ateniesi del IV secolo a.C. (in particolare Cabria, Ificrate, Timoteo e Carete), si intende ora fornire uno sguardo di insieme sulle interpretazioni offerte da Senofonte. L’atteggiamento dello storico nei loro confronti è infatti molto interessante e sembra rientrare nel quadro di una generica volontà di minimizzare la nuova egemonia ateniese e di attribuirne i successi alla crisi spartana, omettendo o solo accennando ad alcuni dei principali fatti politici e militari della storia ateniese di questi anni e obliterandone spesso i suoi principali esponenti. Eppure, accanto allo scarso interesse mostrato da Senofonte nei confronti di Conone, Callistrato o Cabria (le cui imprese sono sistematicamente sminuite), si assiste a un più positivo atteggiamento riguardo a Timoteo e perfino a Carete (solitamente invece disprezzato), fino ad arrivare ad uno stupefacente coinvolgimento nel personaggio di Ificrate, su cui sono celebri le lodi dello storico. Si cercherà dunque di analizzare se e quanto Senofonte abbia contribuito a ricostruire correttamente il quadro delle attività di questi strateghi, confrontandolo con le altre tradizioni e cercando i possibili motivi delle differenze nel suo atteggiamento

Crònica de cine

Abstract not availabl

Reassembling gastrulation

During development, a single cell is transformed into a highly complex organism through progressive cell division, specification and rearrangement. An important prerequisite for the emergence of patterns within the developing organism is to establish asymmetries at various scales, ranging from individual cells to the entire embryo, eventually giving rise to the different body structures. This becomes especially apparent during gastrulation, when the earliest major lineage restriction events lead to the formation of the different germ layers. Traditionally, the unfolding of the developmental program from symmetry breaking to germ layer formation has been studied by dissecting the contributions of different signaling pathways and cellular rearrangements in the in vivo context of intact embryos. Recent efforts, using the intrinsic capacity of embryonic stem cells to self-assemble and generate embryo-like structures de novo, have opened new avenues for understanding the many ways by which an embryo can be built and the influence of extrinsic factors therein. Here, we discuss and compare divergent and conserved strategies leading to germ layer formation in embryos as compared to in vitro systems, their upstream molecular cascades and the role of extrinsic factors in this process