Diversification of a protein kinase cascade: IME-2 is involved in nonself recognition and programmed cell death in Neurospora crassa.

Kinase cascades and the modification of proteins by phosphorylation are major mechanisms for cell signaling and communication, and evolution of these signaling pathways can contribute to new developmental or environmental response pathways. The Saccharomyces cerevisiae kinase Ime2 has been well characterized for its role in meiosis. However, recent studies have revealed alternative functions for Ime2 in both S. cerevisiae and other fungi. In the filamentous fungus Neurospora crassa, the IME2 homolog (ime-2) is not required for meiosis. Here we determine that ime-2 interacts genetically with a transcription factor vib-1 during nonself recognition and programmed cell death (PCD). Mutations in vib-1 (Δvib-1) suppress PCD due to nonself recognition events; however, a Δvib-1 Δime-2 mutant restored wild-type levels of cell death. A role for ime-2 in the post-translational processing and localization of a mitochondrial matrix protein was identified, which may implicate mitochondria in N. crassa nonself recognition and PCD. Further, Δvib-1 strains do not produce extracellular proteases, but protease secretion reverted to near wild-type levels in a Δvib-1 Δime-2 strain. Mass spectrometry analysis revealed that the VIB-1 protein is phosphorylated at several sites, including a site that matches the IME-2 consensus. The genetic and biochemical data for ime-2 and vib-1 indicate that IME-2 is a negative regulator of VIB-1 and suggest parallel negative regulation by IME-2 of a cell death pathway in N. crassa that functions in concert with the VIB-1 cell death pathway. Thus, IME2 kinase function has evolved following the divergence of S. cerevisiae and N. crassa and provides insight into the evolution of kinases and their regulatory targets

The LaTeX project: A case study of open-source software

This is a case study of TeX, a typesetting software that was developed by Donald E. Knuth in the late 70's. Released with an open source license, it has become a reference in scientific publishing. TeX is now used to typeset and publish much of the world's scientific literature in physics and mathematics. This case study is part of a wider effort by academics to understand the open-source phenomenon. That development model is similar to the organization of the production of knowledge in academia; there is no set organization with a hierarchy, but free collaboration that is coordinated spontaneously and winds up generating complex products that are the property of all who can understand its functioning. The case study was led by gathering qualitative data via interviews with TeX developers and quantitative data on the TeX community -- the program's code, the software that is part of the TeX distribution, the newsgroups dedicated to the software, and many other indicators of the evolution and activity in that open-source project. The case study is aimed at economists who want to develop models to understand and analyze the open-source phenomenon. It is also geared towards policy-makers who would like to encourage or regulate open- source, and towards open-source developers who wonder what are the efficient strategies to make an open-source project successful.TeX, LaTeX, case study, open source, software, innovation, organisational structure, economic history, knowledge production, knowledge diffusion.

Differential-Algebraic Equations and Beyond: From Smooth to Nonsmooth Constrained Dynamical Systems

The present article presents a summarizing view at differential-algebraic equations (DAEs) and analyzes how new application fields and corresponding mathematical models lead to innovations both in theory and in numerical analysis for this problem class. Recent numerical methods for nonsmooth dynamical systems subject to unilateral contact and friction illustrate the topicality of this development.Comment: Preprint of Book Chapte

Modelling the pacemaker in event-B: towards methodology for reuse

The cardiac pacemaker is one of the system modelling problems posed to the Formal Methods community by the {\it Grand Challenge for Dependable Systems Evolution} \cite{JOW:06}. The pacemaker is an intricate safety-critical system that supports and moderates the dysfunctional heart's intrinsic electrical control system. This paper focusses on (i) the problem (requirements) domain specification and its mapping to solution (implementation) domain models, (ii) the significant commonality of behaviour between its many operating modes, emphasising the potential for reuse, and (iii) development and verification of models.We introduce the problem and model three of the operating modes in the problem domain using a state machine notation. We then map each of these models into a solution domain state machine notation, designed as shorthand for a refinement-based solution domain development in the Event-B formal language and its RODIN toolki

AMISEC: Leveraging Redundancy and Adaptability to Secure AmI Applications

Security in Ambient Intelligence (AmI) poses too many challenges due to the inherently insecure nature of wireless sensor nodes. However, there are two characteristics of these environments that can be used effectively to prevent, detect, and confine attacks: redundancy and continuous adaptation. In this article we propose a global strategy and a system architecture to cope with security issues in AmI applications at different levels. Unlike in previous approaches, we assume an individual wireless node is vulnerable. We present an agent-based architecture with supporting services that is proven to be adequate to detect and confine common attacks. Decisions at different levels are supported by a trust-based framework with good and bad reputation feedback while maintaining resistance to bad-mouthing attacks. We also propose a set of services that can be used to handle identification, authentication, and authorization in intelligent ambients. The resulting approach takes into account practical issues, such as resource limitation, bandwidth optimization, and scalability

Dynamic Congestion and Tolls with Mobile Source Emission

This paper proposes a dynamic congestion pricing model that takes into account mobile source emissions. We consider a tollable vehicular network where the users selfishly minimize their own travel costs, including travel time, early/late arrival penalties and tolls. On top of that, we assume that part of the network can be tolled by a central authority, whose objective is to minimize both total travel costs of road users and total emission on a network-wide level. The model is formulated as a mathematical program with equilibrium constraints (MPEC) problem and then reformulated as a mathematical program with complementarity constraints (MPCC). The MPCC is solved using a quadratic penalty-based gradient projection algorithm. A numerical study on a toy network illustrates the effectiveness of the tolling strategy and reveals a Braess-type paradox in the context of traffic-derived emission.Comment: 23 pages, 9 figures, 5 tables. Current version to appear in the Proceedings of the 20th International Symposium on Transportation and Traffic Theory, 2013, the Netherland

Genetics and genomic medicine in Argentina

A historical summary of genetics and genomic medicine in Argentina. We go through the achievements and difficulties in the implementation of genetic and genomic services both in academia and health care.Fil: Vishnopolska, Sebastián Alexis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Turjanski, Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Herrera Piñero, Mariana. Banco Nacional de Datos Genéticos; ArgentinaFil: Groisman, Boris. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; ArgentinaFil: Liascovich, Rosa. Red Nacional de Anomalías Congénitas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentin

Protostellar collapse and fragmentation using an MHD GADGET

Although the influence of magnetic fields is regarded as vital in the star formation process, only a few magnetohydrodynamics (MHD) simulations have been performed on this subject within the smoothed particle hydrodynamics (SPH) method. This is largely due to the unsatisfactory treatment of non-vanishing divergence of the magnetic field. Recently smoothed particle magnetohydrodynamics (SPMHD) simulations based on Euler potentials have proven to be successful in treating MHD collapse and fragmentation problems, however these methods are known to have some intrinsical difficulties. We have performed SPMHD simulations based on a traditional approach evolving the magnetic field itself using the induction equation. To account for the numerical divergence, we have chosen an approach that subtracts the effects of numerical divergence from the force equation, and additionally we employ artificial magnetic dissipation as a regularization scheme. We apply this realization of SPMHD to a widely known setup, a variation of the 'Boss & Bodenheimer standard isothermal test case', to study the impact of the magnetic fields on collapse and fragmentation. In our simulations, we concentrate on setups, where the initial magnetic field is parallel to the rotation axis. We examine different field strengths and compare our results to other findings reported in the literature. We are able to confirm specific results found elsewhere, namely the delayed onset of star formation for strong fields, accompanied by the tendency to form only single stars. We also find that the 'magnetic cushioning effect', where the magnetic field is wound up to form a 'cushion' between the binary, aids binary fragmentation in a case, where previously only formation of a single protostar was expected.Comment: 18 pages, 11 figures. Final version (with revisions). Accepted to MNRA