274 research outputs found
Fibroblast activation protein-specific mri provides Improved tumour mapping in an orthotopic model of Prostate cancer compared to prostate specific Membrane antigen
No full textAbstract number PD07-08MRI guided focal therapies of prostate cancer have the potential to reduce treatment related side effects without sacrificing oncological outcomes. Molecular MRI with agents targeted to tumour tissues enhances tumour margin detection and consequently treatment guidance/planning. Prostate specific membrane antigen (PSMA) expression is currently the gold standard for molecular imaging of prostate cancer. Fibroblast activation protein (FAP) is an extracellular transmembrane protein expressed on cells of the tumour microenvironment, particularly in stromal and vascular components. FAP has been gaining momentum as a pan-cancer marker(DOI: 10.2967/jnumed.119.227967) as its overexpression often correlates with cancer severity, including in prostate cancer (DOI: 10.1371/journal.pone.0116683) and has been found to be negligibly expressed in healthy tissue. Our objective was to compare MRI contrast of PSMA-targeting and FAP-targeting magnetic nanoparticles (MNPs) in an orthotopic murine model of prostate cancer.Nicole Dmochowska, Valentina Milanova, Anil Shetty, Ramesh Mukkamala, Madduri Srinivasarao, Eric Walser, Phil Low, and Benjamin Thierr
Altered distribution of neutrophils and Nk cells in collagenase-induced osteoarthritis
No full textPurpose/Objective: Osteoarthritis (OA) is a degenerative joint disease
associated with high disability and pain. The aim of the present study is
to evaluate the distribution and trafficking of neutrophils and NK cells
in an experimental model of osteoarthritis.
Materials and methods: SCID mice received an intra-articular (i.a)
injection of collagenase at the knee joint (CIOA mice). In order to
compare the progression of OA with an acute inflammatory process, a
group of SCID mice were i.a. injected with zymosan (ZIA mice). The
degree of joint damage were determined after H&E and toluidine blue
staining. The distribution of neutrophils and NK cells and the
expression of surface CXCR2, 4 and galectin-9 were evaluated in
lymphoid organs and bodily fluids by flow cytometry at day 7 of the
disease model.
Results: Two populations of neutrophils, LY6Ghigh and LY6Glow were
found in bone marrow (BM) and spleen. While BM LY6Ghigh cells
expressed CXCR 2 and galectin-9, LY6Glow cells were negative for
CXCR 2 and 4 but positive for galectin-9. Down-regulated expression
of CXCR 2, 4 and galectin-9 on LY6Ghigh cells at day 7 of CIOA may
correlate with the mobilization of these cells from the BM. CIOA
NKp46 cells expressed CXCR4 and lost the surface CXCR2 in BM butin a lesser extent than ZIA population. In spleen, CXCR2 and 4
decreased on CIOA LY6Ghigh cells similarly to ZIA cells. LY6Glow
population negative for CXCR2, 4 up-regulated galectin-9 only in
CIOA mice suggesting its specific role in the osteoarthritic process.
CIOA NKp46 cells in spleen down-regulated surface CXCR2 and 4.
The percentages of CXCR 4+ cells in blood were strongly reduced in
CIOA (for NK cells) and ZIA (for NK cells and neutrophils) groups
suggesting that the cells with decreased expression of CXCR 4 can enter
the circulation. A lot of the cells in ZIA synovial fluid were CXCR2+
and had down-modulated CXCR4 while CIOA phenotype was more
similar to control.
Conclusions: Our investigations shed a new light on the mechanism
of LY6G neutrophils and NK cell trafficking in OA. Different
modulations observed on these populations, suggest that the exploration
of these mechanisms in OA could lead to the development of
novel therapeutic strategies for the disease
Precise Call Graph Construction in the Presence of Function Pointers
No full textThe use of pointers creates serious problems for optimizing compilers and software engineering tools. Pointers enable indirect memory accesses through pointer dereferences, as well as indirect procedure calls (e.g., through function pointers in C). Such indirect accesses and calls can be disambiguated with pointer analysis. In this paper we evaluate the precision of a pointer analysis by Zhang et al. [17] for the purposes of call graph construction for C programs with function pointers. The analysis uses an inexpensive, almost-linear, flow- and context-insensitive algorithm. To measure analysis precision, we compare the call graph computed by the analysis with the most precise call graph obtainable by a large category of pointer analyses. Surprisingly, for all our data programs the analysis from [17] achieves the best possible precision. This result indicates that for the purposes of call graph construction, even inexpensive analyses can provide very good precision, and therefore the use of more expensive analyses may not be justified.Technical report DCS-TR-44
Fragment class analysis for testing of polymorphism in Java software
No full textAdequate testing of polymorphism in object-oriented software requires coverage of all possible bindings of receiver classes and target methods at call sites. Tools that measure this coverage need to use class analysis to compute the coverage requirements. However, traditional whole-program class analysis cannot be used when testing partial programs. To solve this problem, we present a general approach for adapting whole-program class analyses to operate on program fragments. Furthermore, since analysis precision is critical for coverage tools, we provide precision measurements for several analyses by determining which of the computed coverage requirements are actually feasible. Our work enables the use of whole-program class analyses for testing of polymorphism in partial programs, and identifies analyses that compute precise coverage requirements and therefore are good candidates for use in coverage tools.Technical report DCS-TR-50
Points-to analysis for Java using annotated inclusion constraints
No full textThe goal of points-to analysis for Java is to determine the set of objects pointed to by a reference variable or a reference object field. In this paper we define and evaluate a points-to analysis for Java which extends Andersen’s points-to analysis for C [4]. Andersen’s analysis for C can be implemented efficiently by using systems of set-inclusion constraints and by employing several techniques for constraint representation and resolution. We extend these techniques to efficiently represent and solve systems of annotated inclusion constraints. The annotations play two roles in our analysis. Method annotations are used to model precisely and efficiently the semantics of virtual calls. Field annotations allow us to distinguish the flow of values through different fields of an object. In addition, our analysis keeps track of all methods reachable from the entry point of the program, and avoids analyzing dead library code. We evaluate the performance of the analysis on a large set of realistic Java programs. Our results show that the analysis is practical and therefore will be useful as a relatively precise general-purpose points-to analysis for Java. The experiments also show that the points-to solution has significant impact on call graph construction, virtual call resolution, elimination of unnecessary synchronization, and stack-based object allocation.Technical report DCS-TR-41
Parameterized object sensitivity for points-to and side-effect analyses for Java
No full textThe goal of points-to analysis for Java is to determine the set of objects pointed to by a reference variable or a reference object field. Improving the precision of practical points-to analysis is important because points-to information has a wide variety of client applications in optimizing compilers and software engineering tools. In this paper we present object sensitivity, a new approach to context-sensitive flow insensitive points-to analysis for Java. The key idea of our approach is to analyze a method separately for each of the objects on which this method is invoked. To ensure flexibility and practicality, we propose a parameterization framework which allows analysis designers to control the cost precision tradeoffs of the object-sensitive analysis. Side-effect analysis determines the memory locations that can be modified by the execution of a program statement. This information is needed for various compiler optimizations and software engineering tools. We present a new form of side-effect analysis for Java which is based on object sensitive points-to analysis. We have implemented one instantiation of our parameterized object-sensitive points-to analysis. We compare this instantiation with a context-insensitive points-to analysis for Java which is based on Andersen’s analysis for C [4]. On a set of 23 realistic Java programs, our experiments show that the two analyses have comparable cost. In some cases the object-sensitive analysis is actually faster than the context sensitive analysis. Our results also show that object sensitivity significantly improves the precision of side-effect analysis, call graph construction, and virtual call resolution. Our empirical results demonstrate that object-sensitive analyses are capable of achieving significantly better precision than context-insensitive ones, while at the same time remaining efficient and practical. Thus, object-sensitive analysis is a better candidate for a relatively precise, practical, general-purpose points-to analysis for Java.Technical report DCS-TR-47
Points-to analysis for Java based on annotated constraints
No full textThe goal of points-to analysis for Java is to determine the set of objects pointed to by a reference variable or a reference object field. In this paper we present a points-to analysis for Java based on Andersen’s points-to analysis for C [5]. Andersen’s analysis can be implemented efficiently by using systems of set-inclusion constraints and by employing several techniques for constraint representation and resolution. We extend these techniques to efficiently represent and solve systems of annotated inclusion constraints. The annotations play two roles in our analysis. Method annotations are used to model precisely and efficiently the semantics of virtual calls. Field annotations allow us to distinguish between different fields of an object. In addition, our analysis keeps track of all reachable methods and avoids analyzing irrelevant library code. We evaluate the performance of the analysis on a large set of realistic Java programs. Our experiments show that the analysis runs in practical time and space, and has significant impact on call graph construction, virtual call resolution, synchronization removal, stack-based object allocation, and object read-write information. The results show that our analysis is a realistic candidate for a relatively precise, practical, general-purpose points-to analysis for Java.Technical report DCS-TR-42
Class analysis for testing of polymorphism in Java software
No full textSeveral coverage criteria have been proposed for testing of polymorphic interactions in object-oriented software. We have built a prototype tool that supports these criteria. This paper describes the overall tool design, and shows how class analysis is used by the tool to compute the coverage requirements. We discuss the importance of analysis precision and the ability to analyze subsets of partial programs. We also show how to modify Rapid Type Analysis [2] to compute the coverage requirements, and present initial empirical evaluation of analysis precision.Technical report DCS-TR-43
Constructing precise object relation diagrams
No full textThe Object Relation Diagram (ORD) of a program is a class interdependence diagram which has important applications in integration testing, integration coverage analysis and regression testing. The precision of the ORD, that is how closely it reflects what actually can occur during program execution, directly affects the efficiency (and therefore the practicality) of its usage. This paper makes three key contributions to the use of ORDs in testing. First, we develop the Extended Object Relation Diagram (ExtORD), a version of the ORD designed for use in integration coverage analysis. The ExtORD shows the specific statement resulting in an interclass dependence and can be easily constructed by extending techniques for ORD construction. Second, we develop a general algorithm for ORD construction, parameterized by class analysis. Third and most importantly, we show empirically that relatively precise class analyses can be used to construct precise ORDs and ExtORDs, whose size improvement over earlier techniques is on average 56%-60% or 34%-38% respectively, (depending on the class analysis). In addition, more precise class analyses substantially reduce the size of class firewalls, that set of classes affected by a change to a particular class, which in turn diminishes the effort required for regression testing.Technical report DCS-TR-48
Precise and practical flow analysis of object-oriented software
No full textProgram flow analysis is a technique which determines properties about the run-time behavior of a program by analyzing its source code. Flow information has a wide variety of uses in optimizing compilers and software tools for software understanding, testing and maintenance. There are two important requirements for a flow analysis to be successfully applied in optimizing compilers and software tools: (i) first the analysis needs to be relatively precise and (ii) the analysis needs to be practical. However, typically there is a tradeoff between analysis precision and analysis practicality. Many existing practical flow analyses are based on inclusion constraints. However, these analyses do not model dimensions of analysis precision that are of crucial importance for the analysis of object-oriented languages and its usability in software tools and compilers. The first contribution of this thesis is the development of annotated inclusion constraints— a general framework that allows relatively precise and at the same time practical analysis of large programs. The annotated constraint system is parameterized by an annotation language and operations on the annotations. The key idea is to take a relatively imprecise flow analysis that can be expressed using non-annotated inclusion constraints, and add a dimension of precision by choosing appropriate annotations and operations on the annotations. Using this approach results in analyses that are substantially more precise while remaining efficient and practical. The second contribution is the formulation and implementation of a field-sensitive points-to analysis for Java in the context of this framework. Points-to analysis for Java is a fundamental flow analysis with a wide variety of uses in optimizing compilers and software tools. Extensive experiments show that our analysis has practical cost and achieves substantial impact on various client applications. Another contribution is the development of object sensitivity, a new form of context sensitivity for object-oriented languages. We have formulated and implemented several object-sensitive points-to analyses for Java as instances of the framework for annotated constraints. The empirical results show that object sensitivity substantially improves the precision of points-to and side-effect analyses over context-insensitive analyses. At the same time, the annotations model context sensitivity efficiently, achieving practical cost, comparable to the cost of context-insensitive analysis. The last contribution is the application of relatively precise flow analysis for the construction of interclass dependence diagrams (to be used in integration and regression testing, impact analysis, reverse engineering, etc.). We have developed a general algorithm for diagram construction, and have shown empirically that using field-sensitive points-to analysis improves diagram precision substantially compared to earlier work. The enhanced precision improves the usability of the diagrams in software tools.Technical report DCS-TR-53
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