Cell-cell communication in early developing seeds of Arabidopsis thaliana

Sexual reproduction and the formation of seeds are key events in the life cycle of flowering plants. The development of the seed is achieved through the coordinated growth of its three components: embryo, endosperm and maternal integuments. Recent genetic studies have revealed that the tight co-ordination of the growth of the three tissues is mediated by cell-cell communication, most likely involving transmembrane receptors and secreted peptides that act as ligands. However, precisely which proteins are involved and how their activities are regulated remains poorly understood. The aim of my thesis is to investigate the putative roles of receptor like kinases (RLKs) in the coordination of growth during early seed development. Although there are 600 RLKs in the Arabidopsis genome, only a few of them have been assigned with a biological function. Mutation in one leucine-rich-repeat RLK (IKU2) gene confers a small seed phenotype. To decipher the role of IKU2 during seed development and reveal its interaction with other receptor kinases known to play a key role during plant reproduction and development, genetic analyses were performed with SERK1/SERK2, EMS1/EXS, ERECTA and the newly identified IKU2-LIKE. The results from these analyses, suggest that both IKU2 and ERECTA genetically interact to regulate seed size. Interestingly, this work has also revealed that an IKU2 homologue, named IKU2- LIKE (IKL), as well as EMS1 also genetically interact with IKU2 and play a role in seed development. To better understand the function of the IKU2 receptor kinase a biochemical analysis was conducted, which revealed that the kinase domain is strictly required for IKU2 function. Together these findings support a pivotal role for IKU2 and associated receptor like kinases, specifically ERECTA, in regulating the co-ordinated growth and development of the Arabidopsis seed

Machine-Checked Proofs For Realizability Checking Algorithms

Virtual integration techniques focus on building architectural models of systems that can be analyzed early in the design cycle to try to lower cost, reduce risk, and improve quality of complex embedded systems. Given appropriate architectural descriptions, assume/guarantee contracts, and compositional reasoning rules, these techniques can be used to prove important safety properties about the architecture prior to system construction. For these proofs to be meaningful, each leaf-level component contract must be realizable; i.e., it is possible to construct a component such that for any input allowed by the contract assumptions, there is some output value that the component can produce that satisfies the contract guarantees. We have recently proposed (in [1]) a contract-based realizability checking algorithm for assume/guarantee contracts over infinite theories supported by SMT solvers such as linear integer/real arithmetic and uninterpreted functions. In that work, we used an SMT solver and an algorithm similar to k-induction to establish the realizability of a contract, and justified our approach via a hand proof. Given the central importance of realizability to our virtual integration approach, we wanted additional confidence that our approach was sound. This paper describes a complete formalization of the approach in the Coq proof and specification language. During formalization, we found several small mistakes and missing assumptions in our reasoning. Although these did not compromise the correctness of the algorithm used in the checking tools, they point to the value of machine-checked formalization. In addition, we believe this is the first machine-checked formalization for a realizability algorithm.Comment: 14 pages, 1 figur

Algebraic totality, towards completeness

Finiteness spaces constitute a categorical model of Linear Logic (LL) whose objects can be seen as linearly topologised spaces, (a class of topological vector spaces introduced by Lefschetz in 1942) and morphisms as continuous linear maps. First, we recall definitions of finiteness spaces and describe their basic properties deduced from the general theory of linearly topologised spaces. Then we give an interpretation of LL based on linear algebra. Second, thanks to separation properties, we can introduce an algebraic notion of totality candidate in the framework of linearly topologised spaces: a totality candidate is a closed affine subspace which does not contain 0. We show that finiteness spaces with totality candidates constitute a model of classical LL. Finally, we give a barycentric simply typed lambda-calculus, with booleans ${\mathcal{B}}$ and a conditional operator, which can be interpreted in this model. We prove completeness at type ${\mathcal{B}}^n\to{\mathcal{B}}$ for every n by an algebraic method

Brain region-specific expression of genes mapped within quantitative trait loci for behavioral responsiveness to acute stress in Fisher 344 and Wistar Kyoto male rats

Acute stress responsiveness is a quantitative trait that varies in severity from one individual to another; however, the genetic component underlying the individual variation is largely unknown. Fischer 344 (F344) and Wistar Kyoto (WKY) rat strains show large differences in behavioral responsiveness to acute stress, such as freezing behavior in response to footshock during the conditioning phase of contextual fear conditioning (CFC). Quantitative trait loci (QTL) have been identified for behavioral responsiveness to acute stress in the defensive burying (DB) and open field test (OFT) from a reciprocal F2 cross of F344 and WKY rat strains. These included a significant QTL on chromosome 6 (Stresp10). Here, we hypothesized that the Stresp10 region harbors genes with sequence variation(s) that contribute to differences in multiple behavioral response phenotypes between the F344 and WKY rat strains. To test this hypothesis, first we identified differentially expressed genes within the Stresp10 QTL in the hippocampus, amygdala, and frontal cortex of F344 and WKY male rats using genome-wide microarray analyses. Genes with both expression differences and non-synonymous sequence variations in their coding regions were considered candidate quantitative trait genes (QTGs). As a proof-of-concept, the F344.WKY-Stresp10 congenic strain was generated with the Stresp10 WKY donor region into the F344 recipient strain. This congenic strain showed behavioral phenotypes similar to those of WKYs. Expression patterns of Gpatch11 (G-patch domain containing 11), Cdkl4 (Cyclin dependent kinase like 4), and Drc1 (Dynein regulatory complex subunit 1) paralleled that of WKY in the F344.WKY-Stresp10 strain matching the behavioral profiles of WKY as opposed to F344 parental strains. We propose that these genes are candidate QTGs for behavioral responsiveness to acute stress

Stratified Abstraction of Access Control Policies

The shift to cloud-based APIs has made application security critically depend on understanding and reasoning about policies that regulate access to cloud resources. We present stratified predicate abstraction, a new approach that summarizes complex security policies into a compact set of positive and declarative statements that precisely state who has access to a resource. We have implemented stratified abstraction and deployed it as the engine powering AWS’s IAM Access Analyzer service, and hence, demonstrate how formal methods and SMT can be used for security policy explanation

Needle & knot : binder boilerplate tied up

To lighten the burden of programming language mechanization, many approaches have been developed that tackle the substantial boilerplate which arises from variable binders. Unfortunately, the existing approaches are limited in scope. They typically do not support complex binding forms (such as multi-binders) that arise in more advanced languages, or they do not tackle the boilerplate due to mentioning variables and binders in relations. As a consequence, the human mechanizer is still unnecessarily burdened with binder boilerplate and discouraged from taking on richer languages. This paper presents Knot, a new approach that substantially extends the support for binder boilerplate. Knot is a highly expressive language for natural and concise specification of syntax with binders. Its meta-theory constructively guarantees the coverage of a considerable amount of binder boilerplate for well-formed specifications, including that for well-scoping of terms and context lookups. Knot also comes with a code generator, Needle, that specializes the generic boilerplate for convenient embedding in COQ and provides a tactic library for automatically discharging proof obligations that frequently come up in proofs of weakening and substitution lemmas of type-systems. Our evaluation shows, that Needle & Knot significantly reduce the size of language mechanizations (by 40% in our case study). Moreover, as far as we know, Knot enables the most concise mechanization of the POPLmark Challenge (1a + 2a) and is two-thirds the size of the next smallest. Finally, Knot allows us to mechanize for instance dependentlytyped languages, which is notoriously challenging because of dependent contexts and mutually-recursive sorts with variables

Software engineering processes for self-adaptive systems

In this paper, we discuss how for self-adaptive systems some activities that traditionally occur at development-time are moved to run-time. Responsibilities for these activities shift from software engineers to the system itself, causing the traditional boundary between development-time and run-time to blur. As a consequence, we argue how the traditional software engineering process needs to be reconceptualized to distinguish both development-time and run-time activities, and to support designers in taking decisions on how to properly engineer such systems. Furthermore, we identify a number of challenges related to this required reconceptualization, and we propose initial ideas based on process modeling. We use the Software and Systems Process Engineering Meta-Model (SPEM) to specify which activities are meant to be performed off-line and on-line, and also the dependencies between them. The proposed models should capture information about the costs and benefits of shifting activities to run-time, since such models should support software engineers in their decisions when they are engineering self-adaptive systems

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%