Application of process algebraic verification and reduction techniques to SystemC designs

SystemC is an IEEE standard system-level language used in hardware/software codesign and has been widely adopted in the industry. This paper describes a formal approach to verifying SystemC designs by providing a mapping to the process algebra mCRL2. Our mapping formalizes both the simulation semantics as well as exhaustive state-space exploration of SystemC designs. By exploiting the existing reduction techniques of mCRL2 and also its model-checking tools, we efficiently locate the race conditions in a system and resolve them. A tool is implemented to automatically perform the proposed mapping. This mapping and the implemented tool enabled us to exploit process-algebraic verification techniques to analyze a number of case-studies, including the formal analysis of a single-cycle and a pipelined MIPS processor specified in SystemC.

A new class of mixed monotone operators with concavity and applications to fractional differential equations

In this article, we investigate a class of mixed monotone operators with concavity on ordered Banach spaces. As applications, we utilize the main results obtained in this paper to study for solutions of fractional differential equations. An example is also considered to illustrate the main result.Publisher's Versio

Folate-conjugated nanoparticles as a potent therapeutic approach in targeted cancer therapy

The selective and efficient drug delivery to tumor cells can remarkably improve different cancer therapeutic approaches. There are several nanoparticles (NPs) which can act as a potent drug carrier for cancer therapy. However, the specific drug delivery to cancer cells is an important issue which should be considered before designing new NPs for in vivo application. It has been shown that cancer cells over-express folate receptor (FR) in order to improve their growth. As normal cells express a significantly lower levels of FR compared to tumor cells, it seems that folate molecules can be used as potent targeting moieties in different nanocarrier-based therapeutic approaches. Moreover, there is evidence which implies folate-conjugated NPs can selectively deliver anti-tumor drugs into cancer cells both in vitro and in vivo. In this review, we will discuss about the efficiency of different folate-conjugated NPs in cancer therapy. © 2015, International Society of Oncology and BioMarkers (ISOBM)

Interprocedural Reachability for Flat Integer Programs

We study programs with integer data, procedure calls and arbitrary call graphs. We show that, whenever the guards and updates are given by octagonal relations, the reachability problem along control flow paths within some language w1* ... wd* over program statements is decidable in Nexptime. To achieve this upper bound, we combine a program transformation into the same class of programs but without procedures, with an Np-completeness result for the reachability problem of procedure-less programs. Besides the program, the expression w1* ... wd* is also mapped onto an expression of a similar form but this time over the transformed program statements. Several arguments involving context-free grammars and their generative process enable us to give tight bounds on the size of the resulting expression. The currently existing gap between Np-hard and Nexptime can be closed to Np-complete when a certain parameter of the analysis is assumed to be constant.Comment: 38 pages, 1 figur

Proving Safety with Trace Automata and Bounded Model Checking

Loop under-approximation is a technique that enriches C programs with additional branches that represent the effect of a (limited) range of loop iterations. While this technique can speed up the detection of bugs significantly, it introduces redundant execution traces which may complicate the verification of the program. This holds particularly true for verification tools based on Bounded Model Checking, which incorporate simplistic heuristics to determine whether all feasible iterations of a loop have been considered. We present a technique that uses \emph{trace automata} to eliminate redundant executions after performing loop acceleration. The method reduces the diameter of the program under analysis, which is in certain cases sufficient to allow a safety proof using Bounded Model Checking. Our transformation is precise---it does not introduce false positives, nor does it mask any errors. We have implemented the analysis as a source-to-source transformation, and present experimental results showing the applicability of the technique

A simple abstraction of arrays and maps by program translation

We present an approach for the static analysis of programs handling arrays, with a Galois connection between the semantics of the array program and semantics of purely scalar operations. The simplest way to implement it is by automatic, syntactic transformation of the array program into a scalar program followed analysis of the scalar program with any static analysis technique (abstract interpretation, acceleration, predicate abstraction,.. .). The scalars invariants thus obtained are translated back onto the original program as universally quantified array invariants. We illustrate our approach on a variety of examples, leading to the " Dutch flag " algorithm

Wnt5a induces ROR1 to associate with 14-3-3ζ for enhanced chemotaxis and proliferation of chronic lymphocytic leukemia cells.

Wnt5a can activate Rho GTPases in chronic lymphocytic leukemia (CLL) cells by inducing the recruitment of ARHGEF2 to ROR1. Mass spectrometry on immune precipitates of Wnt5a-activated ROR1 identified 14-3-3ζ, which was confirmed by co-immunoprecipitation. The capacity of Wnt5a to induce ROR1 to complex with 14-3-3ζ could be blocked in CLL cells by treatment with cirmtuzumab, a humanized mAb targeting ROR1. Silencing 14-3-3ζ via small interfering RNA impaired the capacity of Wnt5a to: (1) induce recruitment of ARHGEF2 to ROR1, (2) enhance in vitro exchange activity of ARHGEF2 and (3) induce activation of RhoA and Rac1 in CLL cells. Furthermore, CRISPR/Cas9 deletion of 14-3-3ζ in ROR1-negative CLL cell-line MEC1, and in MEC1 cells transfected to express ROR1 (MEC1-ROR1), demonstrated that 14-3-3ζ was necessary for the growth/engraftment advantage of MEC1-ROR1 over MEC1 cells. We identified a binding motif (RSPS857SAS) in ROR1 for 14-3-3ζ. Site-directed mutagenesis of ROR1 demonstrated that serine-857 was required for the recruitment of 14-3-3ζ and ARHGEF2 to ROR1, and activation of RhoA and Rac1. Collectively, this study reveals that 14-3-3ζ plays a critical role in Wnt5a/ROR1 signaling, leading to enhanced CLL migration and proliferation