bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ravenscar‐Java: a high‐integrity profile for real‐time Java
Authors: Kwon Jagun , Wellings Andy , King Steve 
Published: February 2005

AbstractFor many, Java is the antithesis of a high‐integrity programming language. Its combination of object‐oriented programming features, its automatic garbage collection, and its poor support for real‐time multi‐threading are all seen as particular impediments. The Real‐Time Specification for Java has introduced many new features that help in the real‐time domain. However, the expressive power of these features means that very complex programming models can be created, necessitating complexity in the supporting real‐time virtual machine. Consequently, Java, with the real‐time extensions as they stand, seems too complex for confident use in high‐integrity systems. This paper presents a Java profile for the development of software‐intensive high‐integrity real‐time systems. This restricted programming model removes language features with high overheads and complex semantics, on which it is hard to perform timing and functional analyses. The profile fits within the J2ME framework and is consistent with well‐known guidelines for high‐integrity software development, such as those defined by the U.S. Nuclear Regulatory Commission. Copyright © 2005 John Wiley & Sons, Ltd.
Improving the memory management performance of RTSJ
Authors: Higuera‐Toledano M. Teresa , Issarny Valérie 
Published: February 2005

AbstractFrom a real‐time perspective, the garbage collector (GC) introduces unpredictable pauses that are not tolerated by real‐time tasks. Real‐time collectors eliminate this problem but introduce a high overhead. Another approach is to use memory regions (MRs) within which allocation and deallocation is customized. This facility is supported by the memory model of the Real‐Time Specification for Java (RTSJ). RTSJ imposes strict access and assignment rules to avoid both the dangling inter‐region references and the delays of critical tasks of the GC. A dynamic check solution can incur high overhead, which can be reduced by taking advantage of hardware features. This paper provides an in‐depth analytical investigation of the overhead introduced by dynamic assignments checks in RTSJ, describing and analysing several solutions to reduce the introduced overhead. Copyright © 2005 John Wiley & Sons, Ltd.
Elimination of Java array bounds checks in the presence of indirection
Authors: Luján Mikel , Gurd John R. , Freeman T. L. , Miguel José 
Published: February 2005

AbstractThe Java language specification states that every access to an array needs to be within the bounds of that array, i.e. between 0 and array length − 1. Different techniques for different programming languages have been proposed to eliminate explicit bounds checks. Some of these techniques are implemented in off‐the‐shelf Java Virtual Machines (JVMs). The underlying principle of these techniques is that bounds checks can be removed when a JVM/compiler has enough information to guarantee that a sequence of accesses (e.g. inside a for‐loop) is safe (within the bounds). Most of the techniques for the elimination of array bounds checks have been developed for programming languages that do not support multi‐threading and/or enable dynamic class loading. These two characteristics make most of these techniques unsuitable for Java. Techniques developed specifically for Java have not addressed the elimination of array bounds checks in the presence of indirection; that is, when the index is stored in another array (indirection array). With the objective of optimizing applications with array indirection, this paper proposes and evaluates three implementation strategies, each implemented as a Java class. The classes provide the functionality of Java arrays of type int so that objects of the classes can be used instead of indirection arrays. Each strategy enables JVMs, when examining only one of these classes at a time, to obtain enough information to remove array bounds checks. Copyright © 2005 John Wiley & Sons, Ltd.
Compiling almost‐whole Java programs
Authors: Budimlić Zoran , Kennedy Ken 
Published: February 2005

AbstractThis paper presents a strategy, called almost‐whole‐program compilation, for extending the benefits of whole‐program optimization to large collections of Java components that are packaged as a group after the development phase. This strategy has been implemented in a framework that uses Java visibility and scoping rules to transform a collection of classes into a package that is amenable to whole‐program optimizations, without precluding extensions to the optimized and compiled code. Thus, it enables the Java developer to balance performance against flexibility of the program after the development phase, without compromising the design process. The transformation is shown to incur only modest performance penalties, which are more than compensated for by the interprocedural optimizations it enables. The paper concludes with experimental results showing the benefits that can be achieved using this approach. Copyright © 2005 John Wiley & Sons, Ltd.
Recurrence analysis for effective array prefetching in Java
Authors: Cahoon Brendon , McKinley Kathryn S. 
Published: February 2005

AbstractJava is an attractive choice for numerical, as well as other, algorithms due to the software engineering benefits of object‐oriented programming. Because numerical programs often use large arrays that do not fit in the cache, they suffer from poor memory performance. To hide memory latency, we describe a new unified compile‐time analysis for software prefetching arrays and linked structures in Java. Our previous work used data‐flow analysis to discover linked data structure accesses. We generalize our prior approach to identify loop induction variables as well, which we call recurrence analysis. Our algorithm schedules prefetches for all array references that contain induction variables. We evaluate our technique using a simulator of an out‐of‐order superscalar processor running a set of array‐based Java programs. Across all of our programs, prefetching reduces execution time by a geometric mean of 23%, and the largest improvement is 58%. We also evaluate prefetching on a PowerPC processor, and we show that prefetching reduces execution time by a geometric mean of 17%. Because our analysis is much simpler and quicker than previous techniques, it is suitable for including in a just‐in‐time compiler. Traditional software prefetching algorithms for C and Fortran use locality analysis and sophisticated loop transformations. We further show that the additional loop transformations and careful scheduling of prefetches from previous work are not always necessary for modern architectures and Java programs. Copyright © 2005 John Wiley & Sons, Ltd.
The Open Runtime Platform: a flexible high‐performance managed runtime environment
Authors: Cierniak Michal , Eng Marsha , Glew Neal , Lewis Brian , Stichnoth James 
Published: February 2005

AbstractThe Open Runtime Platform (ORP) is a high‐performance managed runtime environment (MRTE) that features exact generational garbage collection, fast thread synchronization, and multiple coexisting just‐in‐time compilers (JITs). ORP was designed for flexibility in order to support experiments in dynamic compilation, garbage collection, synchronization, and other technologies. It can be built to run either Java or Common Language Infrastructure (CLI) applications, to run under the Windows or Linux operating systems, and to run on the IA‐32 or Itanium processor family (IPF) architectures. Achieving high performance in a MRTE presents many challenges, particularly when flexibility is a major goal. First, to enable the use of different garbage collectors and JITs, each component must be isolated from the rest of the environment through a well‐defined software interface. Without careful attention, this isolation could easily harm performance. Second, MRTEs have correctness and safety requirements that traditional languages such as C++ lack. These requirements, including null pointer checks, array bounds checks, and type checks, impose additional runtime overhead. Finally, the dynamic nature of MRTEs makes some traditional compiler optimizations, such as devirtualization of method calls, more difficult to implement or more limited in applicability. To get full performance, JITs and the core virtual machine (VM) must cooperate to reduce or eliminate (where possible) these MRTE‐specific overheads. In this paper, we describe the structure of ORP in detail, paying particular attention to how it supports flexibility while preserving high performance. We describe the interfaces between the garbage collector, the JIT, and the core VM; how these interfaces enable multiple garbage collectors and JITs without sacrificing performance; and how they allow the JIT and the core VM to reduce or eliminate MRTE‐specific performance issues. Copyright © 2005 John Wiley & Sons, Ltd.
Experience in integrating Java with C# and .NET
Authors: Bishop Judith , Horspool R. Nigel , Worrall Basil 
Published: February 2005

AbstractJava programmers cannot help but be aware of the advent of C#, the .NET network environment, and a host of new supporting technologies, such as Web services. Before taking the big step of moving all development to a new environment, programmers will want to know what are the advantages of C# as a language over Java, and whether the new and interesting features of C# and .NET can be incorporated into existing Java software. This paper surveys the advantages of C# and then presents and evaluates experience with connecting it to Java in a variety of ways. The first way provides evidence that Java can be linked to C# at the native code level, albeit through C++ wrappers. The second is a means for retaining the useful applet feature of Java in the server‐side architecture of Web services written in C#. The third is by providing a common XML‐based class for the development of graphical user interfaces (GUIs), which can be incorporated into Java or C#. An added advantage of this system, called Views, is that it can run independently of the resource‐intensive development environment that would otherwise be needed for using C#. A major advantage of the methods described in this paper is that in all cases the Java program is not affected by the fact that it is interfacing with C#. The paper concludes that there are many common shared technologies that bring Java and C# close together, and that innovative ways of using others can open up opportunities not hitherto imagined. Copyright © 2005 John Wiley & Sons, Ltd.
The Mycobacterium tuberculosis cell wall component mycolic acid elicits pathogen‐associated host innate immune responses
Authors: Korf Johanna , Stoltz Anton , Verschoor Jan , De Baetselier Patrick , Grooten Johan 
Published: February 2005

AbstractRecognition of conserved pathogen‐associated molecular patterns constitutes a crucial step in the initiation of innate immune responses. We studied the contribution to the host‐pathogen interaction of mycolic acid (MA), a major lipid component of the cell envelope of the macrophage intracellular pathogen Mycobacterium tuberculosis and other mycobacteria. MA administered to the peritoneal cavity or to the airways induced a unique macrophage morphotype, similar to the foamy macrophage derivatives observed in tuberculous granulomas and characterized by intracellular accumulation of neutral lipids and entry into mitosis. When assayed for production of inflammatory mediators, a conditioning rather than a direct activation of the MA‐elicited foamy macrophages was observed. MA enabled production of IFN‐γ and myeloperoxidase, enhanced TNF‐α production and suppressed IL‐10 upon renewed exposure to innate triggers. Intratracheal instillation of MA mimicked additional features of the airway response to M. tuberculosis infection, namely a rapid but transient neutrophil influx and IL‐6 production and a chronic IL‐12 production. These MA‐elicited cellular innate defenses and the accompanying formation of foamy macrophages identify for the first time the foamy macrophage morphotype as part of the host response to a pathogen‐associated structure. Furthermore, these results characterize MA as a direct trigger of innate immunity, distinct from Toll‐like receptor ligands.
Long‐term loss of canonical NKT cells following an acute virus infection
Authors: Lin Yinling , Roberts Tonya J. , Wang Chyung‐Ru , Cho Sungyoo , Brutkiewicz Randy R. 
Published: February 2005

AbstractNKT cell activation plays an important role in regulating innate and adaptive immunity during infection. We have previously found that there is a dramatic reduction in the NKT cell population on day 3 after an acute lymphocytic choriomeningitis virus (LCMV) infection. In this study, we report that this loss continued for at least 3 months and was not simply due to internalization of the TCR. Concomitant with the decrease in NKT cells was an increase in the percentage of Annexin V+ NKT cells that remained in vivo, suggesting that the reduction in NKT cells at these late stages post‐infection occurred by activation‐induced cell death. Interestingly, APC from LCMV‐infected mice could activate NKT cells in vitro at higher levels than those from uninfected mice and was concomitant with an increase in apoptosis in NKT cells. However, this could not be blocked by mAb to murine CD1d, and APC from LCMV‐infected (but not uninfected) CD1d1‐deficient mice could also stimulate NKT cells. Collectively, our data suggest that the activation and subsequent long‐term loss of NKT cells is a normal component of the host's antiviral immune response, and this occurs in a CD1d‐independent manner.
MyD88 is critical for the development of innate and adaptive immunity during acute lymphocytic choriomeningitis virus infection
Authors: Zhou Shenghua , Kurt‐Jones Evelyn A. , Mandell Leisa , Cerny Anna , Chan Melvin , Golenbock Douglas T. , Finberg Robert W. 
Published: February 2005

AbstractWe investigated the roles of Toll‐like receptor 2 (TLR2) and myeloid differentiation factor 88 (MyD88) in the course of a lymphocytic choriomeningitis virus (LCMV) infection and revealed the following: (i) studies of transfected cells and murine peritoneal macrophages demonstrated that TLR2 and MyD88 are essential for the initial pro‐inflammatory cytokine response (human IL‐8, mouse IL‐6) to LCMV; (ii) TLR2 knockout (KO) mice and MyD88 KO mice challenged with LCMV produced less IL‐6 and monocyte chemotactic protein‐1 in the serum than wild‐type mice; (iii) in contrast to inflammatory cytokines, the production of type 1 IFN (IFN‐α) in response to LCMV was MyD88 independent; (iv) MyD88 plays an essential role in antiviral CD8+ T cell responses, CD8+ T cells in MyD88 KO mice were defective in their expression of intracellular antiviral cytokines; and (v) the failure of MyD88 KO mice to activate CD8+ T cells was accompanied by persistent viral infection in MyD88 KO mice. We demonstrate that TLR‐mediated responses are important in the innate immune response to LCMV and that MyD88 is essential for the control of the LCMV infection and the maturation/activation of virus‐specific CD8+ T cells.
Novel method for detection of virus‐specific CD4+ T cells indicates a decreased EBV‐specific CD4+ T cell response in untreated HIV‐infected subjects
Authors: Piriou Erwan R. , van Dort Karel , Nanlohy Nening M. , van Oers Marinus H. , Miedema Frank , van Baarle Debbie 
Published: February 2005

AbstractA lower function of EBV‐specific CD8+ T cells in HIV‐infected subjects could be related to a lack of specific CD4+ T cell help. Therefore, we studied EBV‐specific CD4+ T cells in both healthy donors and untreated or highly active antiretroviral therapy (HAART)‐treated HIV‐seropositive homosexual men. To this end, PBMC were stimulated with overlapping peptide pools from a latent and a lytic EBV protein, EBV nuclear antigen (EBNA)1 and EBV lytic‐switch protein ZEBRA (BZLF1), respectively. EBV‐specific CD4+ T cell frequencies measured directly ex vivo were low. To measure EBV‐specific memory CD4+ T cells, capable of both expansion and IFN‐γ production upon antigenic challenge, we developed a specific and reproducible assay, combining ex vivo expansion of specific T cells with flow cytometric analysis of IFN‐γ production. Untreated HIV‐infected individuals had a lower CD4+ T cell response to both EBNA1 and BZLF1 as compared to healthy EBV carriers and HAART‐treated HIV‐positive subjects. This suggests loss of EBV‐specific CD4+ T cells due to HIV infection, while HAART might restore this response. In addition, we found an increase in the EBNA1‐specific CD8+ T cell response in HAART‐treated subjects. Interestingly, numbers of EBV‐specific CD4+ and CD8+ T cells were inversely correlated with EBV viral load, suggesting an important role also for EBV‐specific CD4+ T cells in the control of EBV infection.
Endogenous association of Bim BH3‐only protein with Mcl‐1, Bcl‐xL and Bcl‐2 on mitochondria in human B cells
Authors: Gomez‐Bougie Patricia , Bataille Régis , Amiot Martine 
Published: February 2005

AbstractBim is an essential regulator of lymphoid system homeostasis and appears essential for B cell apoptosis induction. The mechanism by which Bim isoforms are held in an inactive form remains poorly documented in normal B cells. In the current study, we demonstrated that in normal tonsil B cells the three major Bim isoforms are strongly associated with the anti‐apoptotic Bcl‐2 family members Mcl‐1, Bcl‐2 and Bcl‐xL. On the other hand, only a weak association of BimEL and L with the dynein LC8 chain has been found. In addition, there is no free Bim in normal B cells. Moreover, subcellular fractionation demonstrated that Bim and the anti‐apoptotic counterparts are localized preferentially in the mitochondria‐rich fraction. The fact that most Bim was found in this fraction supports the hypothesis that it is sequestered by anti‐apoptotic molecules in mitochondria where its pro‐apoptotic activity is controlled. Of interest, BimS is essentially complexed to Mcl‐1 and the Mcl‐1/Bim complex is the most abundant among the three types of complexes. This supports the idea that this complex is critical for the control of B cell death. In conclusion, these results favor a model in which Bim release from anti‐apoptotic proteins is a critical event for initiation of apoptosis.
Definitive radiotherapy with interstitial implant boost for squamous cell carcinoma of the tongue base
Authors: Karakoyun‐Celik Omur , Norris Charles M. , Tishler Roy , Mahadevan Anand , Clark John R. , Goldberg Saveli , Devlin Phillip , Busse Paul M. 
Published: February 2005

AbstractBackground.The purpose of this study was to examine the long‐term outcome of a cohort of patients with unresected base of tongue carcinoma who received interstitial brachytherapy after comprehensive external beam radiation therapy.Methods.Between 1983 and 2000, 122 patients with primary or recurrent squamous cell carcinoma of the oropharynx or oral cavity received interstitial brachytherapy as part of their overall management. Forty patients had primary, unresected carcinoma of the base of tongue and are the subjects of this analysis. The median age was 54 years. Fifty‐four percent had T3 or T4 disease, and 70% had clinical or radiographic lymphadenopathy. Twenty‐four (60%) received two to three cycles of neoadjuvant chemotherapy. The oropharynx, bilateral neck, and supraclavicular fossae were comprehensively irradiated, and the tongue base received a median external beam dose of 61.2 Gy (50–72 Gy). The primary site was then boosted with an interstitial 192Iridium implant by use of a gold‐button single‐strand technique and three‐dimensional treatment planning. The dose rate was prescribed at 0.4 to 0.5 Gy/hr. The median implant dose was 17.4 Gy (9.6–24 Gy) and adjusted to reach a total dose to the primary tumor of 80 Gy. N2 to 3 disease was managed by a planned neck dissection performed at the time of the implant.Results.The median follow‐up for all patients was 56 months, and the overall survival rates were 62% at 5 years and 27% at 10 years. The actuarial primary site control was 78% at 5 years and 70% at 10 years. The overall survival and primary site control were independent of T classification, N status, or overall stage. Systemic therapy was associated with an improvement in overall survival (p = .04) and a trend toward increased primary site control with greater clinical response. There were seven documented late effects, the most frequent being grade 3 osteonecrosis (n = 2), grade 2 swallowing dysfunction (n = 2), trismus (n = 2), and chronic throat pain (n = 1).Conclusions.In an era of greatly improved dose distributions made possible by three‐dimensional treatment planning and intensity‐modulated radiation therapy, brachytherapy allows a highly conformal dose to be delivered in sites such as the oropharynx. If done properly, the procedure is safe and delivers a dose that is higher than what can be achieved by external beam radiation alone with the expected biologic advantages. The long‐term data presented here support an approach of treating advanced tongue base lesions that includes interstitial brachytherapy as part of the overall management plan. This approach has led to a 78% rate of organ preservation at 5 years, with a 5% incidence of significant late morbidity (osteonecrosis) that has required medical management. © 2005 Wiley Periodicals, Inc. Head Neck 27: XXX–XXX, 2005
In vitro drug release studies of 2‐hydroxyethyl acrylate or 2‐hydroxypropyl methacrylate‐4‐{(1E,4E)‐5‐[4‐(acryloyloxy)phenyl]‐3‐oxopenta‐1,4‐dienyl}phenyl acrylate copolymer beads
Authors: Arun A. , Reddy B.S.R. 
Published: February 2005

Abstract4‐{(1E,4E)‐5‐[4‐(Acryloyloxy)phenyl]‐3‐oxopenta‐1,4‐dienyl}phenyl acrylate (APPA) was synthesized by reacting (1E,4E)‐1,5‐bis(4‐hydroxyphenyl)penta‐1,4‐dien‐3‐one (HPD) and acryloyl chloride using triethylamine as a base. 2′,4‐Dichloro‐5′‐fluoro‐1‐ene‐2‐(4‐hydroxyphenyl)phenone (EHP) (Arun A, Reddy BSR, Rajkumar M. Polymeric drug for antimicrobial activity studies: Synthesis and characterization. J Bioact Compat Polym 2003;18:219) was used for the controlled release studies. Two types of porous hydrogels were prepared by copolymerizing 2‐hydroxyethyl acrylate (HEA) or 2‐hydroxypropyl methacrylate (HPMA) with APPA (as a crosslinker) by employing the suspension polymerization technique. The morphology of the hydrogels were characterized by the optical microscopy (OM) and scanning electron microscopy (SEM). Different variations were employed in the preparation of hydrogels to study the effect of crosslinker percentage and drug the loading percentage. Totally 18 types of hydrogels were prepared. The drug‐releasing pattern was monitored over a period of 4 weeks using the UV spectroscopic technique by measuring the absorptions at 330.5 nm. In vitro release experiments were carried out at pH 7.4 and pH 9.2. In total, 36 releasing experiments were conducted. The results showed that the controlled release of the drug was dependent on the monomer (HEA or HPMA), crosslinker percentage (CLP), drug‐loading percentage (DLP), and pH. The release rate was higher for HEA‐based hydrogels when compared with HPMA‐based hydrogels in all compositions. The release rate was noticeably higher in pH 9.2 than pH 7.4. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater
Finite subgraphs of uncountably chromatic graphs
Authors: Komjáth Péter , Shelah Saharon 
Published: February 2005

AbstractIt is consistent that for every function f:ω → ω there is a graph with size and chromatic number ℵ1 in which every n‐chromatic subgraph contains at least f(n) vertices (n ≥ 3). This solves a $ 250 problem of Erdős. It is consistent that there is a graph X with Chr(X)=|X|=ℵ1 such that if Y is a graph all whose finite subgraphs occur in X then Chr(Y)≤ℵ2 (so the Taylor conjecture may fail). It is also consistent that if X is a graph with chromatic number at least ℵ2 then for every cardinal λ there exists a graph Y with Chr(Y)≥λ all whose finite subgraphs are induced subgraphs of X. © 2005 Wiley Periodicals, Inc. J Graph Theory 49: 28–38, 2005