Proteolysis inhibition by hibernating bear serum leads to increased protein content in human muscle cells

Muscle atrophy is one of the main characteristics of human ageing and physical inactivity, with resulting adverse health outcomes. To date, there are still no efficient therapeutic strategies for its prevention and/or treatment. However, during hibernation, bears exhibit a unique ability for preserving muscle in conditions where muscle atrophy would be expected in humans. Therefore, our objective was to determine whether there are components of bear serum which can control protein balance in human muscles. In this study, we exposed cultured human differentiated muscle cells to bear serum collected during winter and summer periods, and measured the impact on cell protein content and turnover. In addition, we explored the signalling pathways that control rates of protein synthesis and degradation. We show that the protein turnover of human myotubes is reduced when incubated with winter bear serum, with a dramatic inhibition of proteolysis involving both proteasomal and lysosomal systems, and resulting in an increase in muscle cell protein content. By modulating intracellular signalling pathways and inducing a protein sparing phenotype in human muscle cells, winter bear serum therefore holds potential for developing new tools to fight human muscle atrophy and related metabolic disorders

Construction of Abstract Domains for Heterogeneous Properties (Position Paper)

International audienceThe aim of static analysis is to infer invariants about programs that are tight enough to establish semantic properties, like the absence of run-time errors. In the last decades, several branches of the static analysis of imperative programs have made significant progress, such as in the inference of numeric invariants or the computation of data structures properties (using pointer abstractions or shape analyzers). Although simultaneous inference of shape-numeric invariants is often needed, this case is especially challenging and less well explored. Notably, simultaneous shape-numeric inference raises complex issues in the design of the static analyzer itself. We study the modular construction of static analyzers, based on combinations of atomic abstract domains to describe several kinds of memory properties and value properties. Static analysis to infer heterogeneous properties. Static analysis by abstract interpreta-tion [4] utilizes an abstraction to over-approximate (non-computable) sets of program states, using computer-representable elements, that stand for logical properties of con-crete program states. As an example, for numerical properties, the interval abstract domain [4] uses constraints of the form n ≤ x and x ≤ p to describe possible values of variable x, where n, p are scalars. To construct a static analyzer capable of inferring sound approximations of program behaviors, one designs an abstract domain, which consists of an abstraction, and abstract operations for sound post-condition operators, join and widening: 1. An abstraction is defined by a set of abstract elements A and a concretization function γ : A → P(C), which maps each abstract property a into the set of concrete elements γ(a) that satisfy it. The set A of abstract elements will be assumed to be defined by a grammar of admissible logical predicates (e.g., for intervals, a(∈ A) ::= a ∧ a | n ≤ x | x ≤ p). 2. A post-condition operator is a function f : A → A which over-approximates a concrete operation f : C → P(C) encountered in programs (as, e.g., a test)

Shape Analysis for Unstructured Sharing

International audienceShape analysis aims to infer precise structural properties of imperative memory states and has been applied heavily to verify safety properties on imperative code over pointer-based data structures. Recent advances in shape analysis based on separation logic has leveraged sum-marization predicates that describe unbounded heap regions like lists or trees using inductive definitions. Unfortunately, data structures with un-structured sharing, such as graphs, are challenging to describe and reason about in such frameworks. In particular, when the sharing is unstructured, it cannot be described inductively in a local manner. In this paper, we propose a global abstraction of sharing based on set-valued variables that when integrated with inductive definitions enables the specification and shape analysis of structures with unstructured sharing

Laser-based soldering of a high-resolution optical filter instrument for space applications

A laser based soldering technique - Solderjet Bumping - using liquid solder droplets in a flux-free process with localized thermal impact demonstrates the all inorganic, adhesive free attachment of optical components and support structures made of heterogeneous materials for a high-resolution optical filter under harsh environmental conditions. Space applications demand an attachment technology which maintains the precise alignment of bonded components and overcomes challenges of common adhesives such as being more radiation resistant and appropriate for vacuum environments. Besides, stress and strain induced into optical components can deteriorate the wavefront of passing light and therefore reduce the system performance significantly. The presented case study shows the mandatory changes in the design of an optical filter instrument according to the boundary conditions of Solderjet Bumping for different bonding issues. First, a filter window made of N-BK10, covering the optical sensor beneath, is soldered into a frame of DilverP1®. Second, this sub-assembly is aligned w.r.t. to fiducials on a support structure and is attached in this state by soldering as well. The process chain of Solderjet Bumping including cleaning, wettable metallization layer, handling, soldering and inspection is discussed. This multi-material approach requires well-defined reflow energies to melt the spherical shaped solder preforms to create a media-fit joint and to prevent damages on the fragile filter window simultaneously. The findings of process parametrization and environmental testing are presented. The optical performance with respect to stress/strain before and after soldering as well as the alignment state are evaluated using non-contact optical techniques

Soldering and packaging study for an optical filter required for high resolution earth observation space missions

The goal of our study is to optimize the packaging process of an optical sensor module under the space mission requirements. The intention of the project is to develop a generation of optical sensor modules avoiding conventional organic adhesives (standard used technologies). The sensor module, designed by Sodern, consists of three parts: the sensor, the filter frame and the filter. The Solderjet Bumping is planned to be used for assembling KOVAR(29 % Ni, 17 % Co, 54 % Fe) and N-BK10 (Borosilicate-Kronglas, Schott glass) and for assembling KOVAR and KOVAR materials, chosen for this application, and creation of a strong bond between these materials, which should withstand the harsh environmental space conditions

Local Shape Analysis for Overlaid Data Structures

We present a shape analysis for programs that manipulate overlaid data structures which share sets of objects. The abstract domain contains Separation Logic formulas that (1) combine a per-object separating conjunction with a per-field separating conjunction and (2) constrain a set of variables interpreted as sets of objects. The definition of the abstract domain operators is based on a notion of homomorphism between formulas, viewed as graphs, used recently to define optimal decision procedures for fragments of the Separation Logic. Based on a Frame Rule that supports the two versions of the separating conjunction, the analysis is able to reason in a modular manner about non-overlaid data structures and then, compose information only at a few program points, e.g., procedure returns. We have implemented this analysis in a prototype tool and applied it on several interesting case studies that manipulate overlaid and nested linked lists

QUICr: A Reusable Library for Parametric Abstraction of Sets and Numbers

Abstract. This paper introduces QUICr, an abstract domain combinator library that lifts any domain for numbers into an efficient domain for numbers and sets of numbers. As a library, it is useful for inferring relational data invariants in programs that manipulate data structures. As a testbed, it allows easy extension of widening and join heuristics, enabling adaptations to new and varied applications. In this paper we present the architecture of the library, guidelines on how to select heuristics, and an example instantiation of the library using the Apron library to verify set-manipulating programs.