bluuebunny/crossref_metadata_2025 huggingface dataset:
A campus-wide testbed over the TV white spaces
Authors: Chandra Ranveer , Moscibroda Thomas , Bahl Paramvir , Murty Rohan , Nychis George , Wang Xiaohui
Published: December 2011

We have deployed a wireless network that operates in the white spaces of the TV band spectrum and covers most of Microsoft campus in Redmond, WA. Since the campus is large (approximately 1 mile x 1 mile), there are several shuttles that move employees from one building to another. We have used the white spaces network to enable a key productivity scenario on campus - Internet connectivity in campus shuttles. We have modified one such shuttle to operate over the TV band white spaces. A white space radio in this shuttle communicates with two base stations deployed on buildings on campus. Inside the shuttle, we bridge the white space connection to Wi-Fi, so that an employee's laptop that does not have an integrated white space radio can nevertheless connect to the Internet, using Wi-Fi within the shuttle, and white spaces between the shuttle and the base stations. To the best of our knowledge, this is the first network deployed over the TV white spaces.
WiSec' 2011 poster
Authors: Perrey Heiner , Ugus Osman , Westhoff Dirk
Published: December 2011

This is a conceptual study attempting to provide a supplementary security feature based on Merkle's Puzzle (MP) in Bluetooth Low Energy (BLE).
The sequential prison
Authors: Sutherland Ivan
Published: December 2011

We are trapped in a sequential prison. We use sequential character strings to write sequential programs to control sequential computers. No wonder concurrency remains elusive. How did we come to be here? The high cost of vacuum tube logic forced sequence upon early computer builders. Sequential character strings were the economic way to describe what sequential computers should do. Sequential programs controlled the expensive part of the machine, namely logic. The lethargic pace of logic circuits masked the cost of moving data over distance, allowing programming languages to ignore the cost of communication. Today, the time delay and energy cost of communicating over distance dominate modern computers; logic is essentially free. Why then, do programming languages continue to control logic and largely ignore communication? It will take a broad effort to escape our sequential prison, requiring changes in hardware, programming notations and the ways in which they are expressed. Most importantly, it will require recognizing that we are in sequential prison, and planning for an escape.
Safe parallel programming using dynamic dependence hints
Authors: Ke Chuanle , Liu Lei , Zhang Chao , Bai Tongxin , Jacobs Bryan , Ding Chen
Published: December 2011

Speculative parallelization divides a sequential program into possibly parallel tasks and permits these tasks to run in parallel if and only if they show no dependences with each other. The parallelization is safe in that a speculative execution always produces the same output as the sequential execution.

In this paper, we present the dependence hint, an interface for a user to specify possible dependences between possibly parallel tasks. Dependence hints may be incorrect or incomplete but they do not change the program output. The interface extends Cytron's do-across and recent OpenMP ordering primitives and makes them safe and safely composable. We use it to express conditional and partial parallelism and to parallelize large-size legacy code. The prototype system is implemented as a software library. It is used to improve performance by nearly 10 times on average on current multicore machines for 8 programs including 5 SPEC benchmarks.
Sprint
Authors: Raman Arun , Yorsh Greta , Vechev Martin , Yahav Eran
Published: December 2011

Remote data access latency is a significant performance bottleneck in many modern programs that use remote databases and web services. We present Sprint - a run-time system for optimizing such programs by prefetching and caching data from remote sources in parallel to the execution of the original program. Sprint separates the concerns of exposing potentially-independent data accesses from the mechanism for executing them efficiently in parallel or in a batch. In contrast to prior work, Sprint can efficiently prefetch data in the presence of irregular or input-dependent access patterns, while preserving the semantics of the original program.

We used Sprint to automatically improve the performance of several real-world Java programs that access remote databases (MySQL, DB2) and web services (Facebook, IBM's Yellow Pages). Sprint achieves speedups ranging 2.4x to 15.8x over sequential execution, which are comparable to those achieved by manually modifying the program for asynchronous and batch execution of data accesses. Sprint provides a simple interface that allows a programmer to plug in support for additional data sources without modifying the client program.
Asynchronous assertions
Authors: Aftandilian Edward E. , Guyer Samuel Z. , Vechev Martin , Yahav Eran
Published: December 2011

Assertions are a familiar and widely used bug detection technique. Traditional assertion checking, however, is performed synchronously, imposing its full cost on the runtime of the program. As a result, many useful kinds of checks, such as data structure invariants and heap analyses, are impractical because they lead to extreme slowdowns. We present a solution that decouples assertion evaluation from program execution: assertions are checked asynchronously by separate checking threads while the program continues to execute. Our technique guarantees that asynchronous evaluation always produces the same result as synchronous evaluation, even if the program concurrently modifies the program state. The checking threads evaluate each assertion on a consistent snapshot of the program state as it existed at the moment the assertion started.

We implemented our technique in a system called Strobe, which supports asynchronous assertion checking in both single-and multi-threaded Java applications. Strobe runs inside the Java virtual machine and uses copy-on-write to construct snapshots incrementally, on-the-fly. Our system includes all necessary synchronization to support multiple concurrent checking threads, and to prevent data races with the main program threads. We find that asynchronous checking significantly outperforms synchronous checking, incurring tolerable overheads -- in the range of 10% to 50% over no checking at all -- even for heavy-weight assertions that would otherwise result in crushing slowdowns.
Ribbons
Authors: Hoffman Kevin J. , Metzger Harrison , Eugster Patrick
Published: December 2011

The need for programs to execute subcomponents in isolation from each other or with lower privileges is prevalent among today's systems. We introduce ribbons: a shared memory programming model that allows for more implicit sharing of memory than processes but is more restrictive than threads. Ribbons structure the heap into protection domains. Privileges between these protection domains are carefully controlled in order to confine computation. We propose RibbonJ, a backwards-compatible extension of Java, to easily create or port programs to use the ribbons model. We study the progress and isolation properties of a subset of the language. Building on JikesRVM we implement ribbons by leveraging existing memory protection mechanisms in modern hardware and operating systems, avoiding the overhead of inline security checks and read or write barriers. We evaluate efficiency via microbenchmarks and the DaCapo suite, observing minor overhead. Additionally, we refactor Apache Tomcat to use ribbons for application isolation, discuss the refactoring's design and complexity, and evaluate performance using the SPECweb2009 benchmark.
JET
Authors: Li Siliang , Tan Gang
Published: December 2011

Java's type system enforces exception-checking rules that stipulate a checked exception thrown by a method must be declared in the throws clause of the method. Software written in Java often invokes native methods through the use of the Java Native Interface (JNI). Java's type system, however, cannot enforce the same exception-checking rules on Java exceptions raised in native methods. This gap makes Java software potentially buggy and often difficult to debug when an exception is raised in native code. In this paper, we propose a complete static-analysis framework called JET to extend exception-checking rules even on native code. The framework has a two-stage design where the first stage throws away a large portion of irrelevant code so that the second stage, a fine-grained analysis, can concentrate on a small set of code for accurate bug finding. This design achieves both high efficiency and accuracy. We have applied JET on a set of benchmark programs with a total over 227K lines of source code and identified 12 inconsistent native-method exception declarations.
Reactive imperative programming with dataflow constraints
Authors: Demetrescu Camil , Finocchi Irene , Ribichini Andrea
Published: December 2011

Dataflow languages provide natural support for specifying constraints between objects in dynamic applications, where programs need to react efficiently to changes of their environment. Researchers have long investigated how to take advantage of dataflow constraints by embedding them into procedural languages. Previous mixed imperative/dataflow systems, however, require syntactic extensions or libraries of ad hoc data types for binding the imperative program to the dataflow solver. In this paper we propose a novel approach that smoothly combines the two paradigms without placing undue burden on the programmer. In our framework, programmers can define ordinary statements of the imperative host language that enforce constraints between objects stored in special memory locations designated as "reactive". Differently from previous approaches, reactive objects can be of any legal type in the host language, including primitive data types, pointers, arrays, and structures. Statements defining constraints are automatically re-executed every time their input memory locations change, letting a program behave like a spreadsheet where the values of some variables depend upon the values of other variables. The constraint solving mechanism is handled transparently by altering the semantics of elementary operations of the host language for reading and modifying objects. We provide a formal semantics and describe a concrete embodiment of our technique into C/C++, showing how to implement it efficiently in conventional platforms using off-the-shelf compilers. We discuss common coding idioms and relevant applications to reactive scenarios, including incremental computation, observer design pattern, and data structure repair. The performance of our implementation is compared to ad hoc problem-specific change propagation algorithms, as well as to language-centric approaches such as self-adjusting computation and subject/observer communication mechanisms, showing that the proposed approach is efficient in practice.
Enhancing locality for recursive traversals of recursive structures
Authors: Jo Youngjoon , Kulkarni Milind
Published: December 2011

While there has been decades of work on developing automatic, locality-enhancing transformations for regular programs that operate over dense matrices and arrays, there has been little investigation of such transformations for irregular programs, which operate over pointer-based data structures such as graphs, trees and lists. In this paper, we argue that, for a class of irregular applications we call traversal codes, there exists substantial data reuse and hence opportunity for locality exploitation. We develop a novel optimization called point blocking, inspired by the classic tiling loop transformation, and show that it can substantially enhance temporal locality in traversal codes. We then present a transformation and optimization framework called TreeTiler that automatically detects opportunities for applying point blocking and applies the transformation. TreeTiler uses autotuning techniques to determine appropriate parameters for the transformation. For a series of traversal algorithms drawn from real-world applications, we show that TreeTiler is able to deliver performance improvements of up to 245% over an optimized (but non-transformed) parallel baseline, and in several cases, significantly better scalability.
Efficiently speeding up sequential computation through the n-way programming model
Authors: Cledat Romain E. , Kumar Tushar , Pande Santosh
Published: December 2011

With core counts on the rise, the sequential components of applications are becoming the major bottleneck in performance scaling as predicted by Amdahl's law. We are therefore faced with the simultaneous problems of occupying an increasing number of cores and speeding up sequential sections. In this work, we reconcile these two seemingly incompatible problems with a novel programming model called N-way. The core idea behind N-way is to benefit from the algorithmic diversity available to express certain key computational steps. By simultaneously launching in parallel multiple ways to solve a given computation, a runtime can just-in-time pick the best (for example the fastest) way and therefore achieve speedup.

Previous work has demonstrated the benefits of such an approach but has not addressed its inherent waste. In this work, we focus on providing a mathematically sound learning-based statistical model that can be used by a runtime to determine the optimal balance between resources used and benefits obtainable through N-way. We further describe a dynamic culling mechanism to further reduce resource waste.

We present abstractions and a runtime support to cleanly encapsulate the computational-options and monitor their progress. We demonstrate a low-overhead runtime that achieves significant speedup over a range of widely used kernels. Our results demonstrate super-linear speedups in certain cases.
Exploiting coarse-grain speculative parallelism
Authors: Pyla Hari K. , Ribbens Calvin , Varadarajan Srinidhi
Published: December 2011

Speculative execution at coarse granularities (e.g., code-blocks, methods, algorithms) offers a promising programming model for exploiting parallelism on modern architectures. In this paper we present Anumita, a framework that includes programming constructs and a supporting runtime system to enable the use of coarse-grain speculation to improve program performance, without burdening the programmer with the complexity of creating, managing and retiring speculations. Speculations may be composed by specifying surrogate code blocks at any arbitrary granularity, which are then executed concurrently, with a single winner ultimately modifying program state. Anumita provides expressive semantics for winner selection that go beyond time to solution to include user-defined notions of quality of solution. Anumita can be used to improve the performance of hard to parallelize algorithms whose performance is highly dependent on input data. Anumita is implemented as a user-level runtime with programming interfaces to C, C++, Fortran and as an OpenMP extension. Performance results from several applications show the efficacy of using coarse-grain speculation to achieve (a) robustness when surrogates fail and (b) significant speedup over static algorithm choices.
Delegated isolation
Authors: Lublinerman Roberto , Zhao Jisheng , Budimlić Zoran , Chaudhuri Swarat , Sarkar Vivek
Published: December 2011

Isolation---the property that a task can access shared data without interference from other tasks---is one of the most basic concerns in parallel programming. In this paper, we present Aida, a new model of isolated execution for parallel programs that perform frequent, irregular accesses to pointer-based shared data structures. The three primary benefits of Aida are dynamism, safety and liveness guarantees, and programmability. First, Aida allows tasks to dynamically select and modify, in an isolated manner, arbitrary fine-grained regions in shared data structures, all the while maintaining a high level of concurrency. Consequently, the model can achieve scalable parallelization of regular as well as irregular shared-memory applications. Second, the model offers freedom from data races, deadlocks, and livelocks. Third, no extra burden is imposed on programmers, who access the model via a simple, declarative isolation construct that is similar to that for transactional memory. The key new insight in Aida is a notion of delegation among concurrent isolated tasks (known in Aida as assemblies). Each assembly A is equipped with a region in the shared heap that it owns---the only objects accessed by A are those it owns, guaranteeing race-freedom. The region owned by A can grow or shrink flexibly---however, when A needs to own a datum owned by B, A delegates itself, as well as its owned region, to B. From now on, B has the responsibility of re-executing the task A set out to complete. Delegation as above is the only inter-assembly communication primitive in Aida. In addition to reducing contention in a local, data-driven manner, it guarantees freedom from deadlocks and livelocks.

We offer an implementation of Aida on top of the Habanero Java parallel programming language. The implementation employs several novel ideas, including the use of a union-find data structure to represent tasks and the regions that they own. A thorough evaluation using several irregular data-parallel benchmarks demonstrates the low overhead and excellent scalability of Aida, as well as its benefits over existing approaches to declarative isolation. Our results show that Aida performs on par with the state-of-the-art customized implementations of irregular applications and much better than coarse-grained locking and transactional memory approaches.
Freedom before commitment
Authors: Summers Alexander J. , Mueller Peter
Published: December 2011

One of the main purposes of object initialisation is to establish invariants such as a field being non-null or an immutable data structure containing specific values. These invariants are then implicitly assumed by the rest of the implementation, for instance, to ensure that a field may be safely dereferenced or that immutable data may be accessed concurrently. Consequently, letting an object escape from its constructor is dangerous; the escaping object might not yet satisfy its invariants, leading to errors in code that relies on them. Nevertheless, preventing objects entirely from escaping from their constructors is too restrictive; it is often useful to call auxiliary methods on the object under initialisation or to pass it to another constructor to set up mutually-recursive structures.

We present a type system that tracks which objects are fully initialised and which are still under initialisation. The system can be used to prevent objects from escaping, but also to allow safe escaping by making explicit which objects might not yet satisfy their invariants. We designed, formalised and implemented our system as an extension to a non-null type system, but it is not limited to this application. Our system is conceptually simple and requires little annotation overhead; it is sound and sufficiently expressive for many common programming idioms. Therefore, we believe it to be the first such system suitable for mainstream use.
F4F
Authors: Sridharan Manu , Artzi Shay , Pistoia Marco , Guarnieri Salvatore , Tripp Omer , Berg Ryan
Published: December 2011

This paper presents F4F (Framework For Frameworks), a system for effective taint analysis of framework-based web applications. Most modern web applications utilize one or more web frameworks, which provide useful abstractions for common functionality. Due to extensive use of reflective language constructs in framework implementations, existing static taint analyses are often ineffective when applied to framework-based applications. While previous work has included ad hoc support for certain framework constructs, adding support for a large number of frameworks in this manner does not scale from an engineering standpoint.

F4F employs an initial analysis pass in which both application code and configuration files are processed to generate a specification of framework-related behaviors. A taint analysis engine can leverage these specifications to perform a much deeper, more precise analysis of framework-based applications. Our specification language has only a small number of simple but powerful constructs, easing analysis engine integration. With this architecture, new frameworks can be handled with no changes to the core analysis engine, yielding significant engineering benefits.

We implemented specification generators for several web frameworks and added F4F support to a state-of-the-art taint-analysis engine. In an experimental evaluation, the taint analysis enhanced with F4F discovered 525 new issues across nine benchmarks, a harmonic mean of 2.10X more issues per benchmark. Furthermore, manual inspection of a subset of the new issues showed that many were exploitable or reflected bad security practice.
Multicore garbage collection with local heaps
Authors: Marlow Simon , Peyton Jones Simon
Published: December 2011

In a parallel, shared-memory, language with a garbage collected heap, it is desirable for each processor to perform minor garbage collections independently. Although obvious, it is difficult to make this idea pay off in practice, especially in languages where mutation is common. We present several techniques that substantially improve the state of the art. We describe these techniques in the context of a full-scale implementation of Haskell, and demonstrate that our local-heap collector substantially improves scaling, peak performance, and robustness.
A comprehensive evaluation of object scanning techniques
Authors: Garner Robin J. , Blackburn Stephen M. , Frampton Daniel
Published: December 2011

At the heart of all garbage collectors lies the process of identifying and processing reference fields within an object. Despite its key role, and evidence of many different implementation approaches, to our knowledge no comprehensive quantitative study of this design space exists. The lack of such a study means that implementers must rely on `conventional wisdom', hearsay, and their own costly analysis. Starting with mechanisms described in the literature and a variety of permutations of these, we explore the impact of a number of dimensions including: a) the choice of data structure, b) levels of indirection from object to metadata, and c) specialization of scanning code. We perform a comprehensive examination of these tradeoffs on four different architectures using eighteen benchmarks and hardware performance counters. We inform the choice of mechanism with a detailed study of heap composition and object structure as seen by the garbage collector on these benchmarks. Our results show that choice of scanning mechanism is important. We find that a careful choice of scanning mechanism alone can improve garbage collection performance by 16% and total time by 2.5%, on average, over a well tuned baseline. We observe substantial variation in performance among architectures, and find that some mechanisms--particularly specialization, layout of reference fields in objects, and encoding metadata in object headers--yield consistent, significant advantages.
On the theory and potential of LRU-MRU collaborative cache management
Authors: Gu Xiaoming , Ding Chen
Published: December 2011

The goal of cache management is to maximize data reuse. Collaborative caching provides an interface for software to communicate access information to hardware. In theory, it can obtain optimal cache performance.

In this paper, we study a collaborative caching system that allows a program to choose different caching methods for its data. As an interface, it may be used in arbitrary ways, sometimes optimal but probably suboptimal most times and even counter productive. We develop a theoretical foundation for collaborative caches to show the inclusion principle and the existence of a distance metric we call LRU-MRU stack distance. The new stack distance is important for program analysis and transformation to target a hierarchical collaborative cache system rather than a single cache configuration. We use 10 benchmark programs to show that optimal caching may reduce the average miss ratio by 24%, and a simple feedback-driven compilation technique can utilize collaborative cache to realize 50% of the optimal improvement.
Handles revisited
Authors: Kalibera Tomas , Jones Richard
Published: December 2011

Compacting garbage collectors must update
all
references to objects they move. Updating is a lengthy operation but the updates must be transparent to the mutator. The consequence is that no space can be reclaimed until all references have been updated which, in a real-time collector, must be done incrementally. One solution is to replace direct references to objects with handles. Handles offer several advantages to a real-time collector. They eliminate the updating problem. They allow immediate reuse of the space used by evacuated objects. They incur no copy reserve overhead. However, the execution time overhead of handles has led to them being abandoned by most modern systems.

We re-examine this decision in the context of real-time garbage collection, for which several systems with handles have appeared recently. We provide the first thorough study of the overheads of handles, based on an optimised implementation of different handle designs within Ovm's Minuteman real-time collector. We find that with a good set of optimisations handles are not very expensive. We obtained zero overhead over the widely used Brooks-style compacting collector (1.6% and 3.1% on two other platforms) and 9% increase in memory usage. Our optimisations are particularly applicable to mark-compact collectors, but may also be useful to other collectors.
Compartmental memory management in a modern web browser
Authors: Wagner Gregor , Gal Andreas , Wimmer Christian , Eich Brendan , Franz Michael
Published: December 2011

Since their inception, the usage pattern of web browsers has changed substantially. Rather than sequentially navigating static web sites, modern web browsers often manage a large number of simultaneous tabs displaying dynamic web content, each of which might be running a substantial amount of client-side JavaScript code. This environment introduced a new degree of parallelism that was not fully embraced by the underlying JavaScript virtual machine architecture. We propose a novel abstraction for multiple disjoint JavaScript heaps, which we call compartments. We use the notion of document origin to cluster objects into separate compartments.

Objects within a compartment can reference each other directly. Objects across compartments can only reference each other through wrappers. Our approach reduces garbage collection pause times by permitting collection of sub-heaps (compartments), and we can use cross-compartment wrappers to enforce cross origin object access policy.
Protective Effects of Simvastatin, a Lipid Lowering Agent, against Oxidative Damage in Experimental Diabetic Rats
Authors: Mohamadin Ahmed M. , Elberry Ahmed A. , Abdel Gawad Hala S. , Morsy Gehan M. , Al-Abbasi Fahad A.
Published: December 2011

The present study was undertaken to evaluate the possible protective effects of simvastatin (SMV) against oxidative stress in streptozotocin- (STZ)-induced diabetic rats. Diabetes was induced experimentally in rats by i.p. injection of STZ in a dose of 60 mg/kg bwt. After 5 weeks of STZ injection, there were apparent reductions in the animal body weight and significant increase in blood glucose, HbA1c, urea, creatinine, AST, ALT, and lipid profiles with a concomitant decrease in total hemoglobin, plasma glutathione and vitamin C as compared to the control group. The treatment with SMV at a dose (10 mg/kg, orally) normalized all the above-mentioned biochemical parameters in STZ-induced diabetic rats.In vitrostudies confirmed the free radical scavenging and antioxidant activity of SMV. Therefore, the present results revealed that SMV has a protective effect against STZ-induced oxidative damage by scavenging the free radicals generation and restoring the enzymatic and nonenzymatic antioxidant systems.
The Oxytocin-Oxytocin Receptor System and Its Antagonists as Tocolytic Agents
Authors: Vrachnis Nikolaos , Malamas Fotodotis M. , Sifakis Stavros , Deligeoroglou Efthymios , Iliodromiti Zoe
Published: December 2011

Oxytocin, a hormone involved in numerous physiologic processes, plays a central role in the mechanisms of parturition and lactation. It acts through its receptor, which belongs to the G-protein-coupled receptor superfamily, while Gq/phospholipase C (PLC)/inositol 1,4,5-triphosphate (InsP3) is the main pathway via which it exerts its action in the myometrium. Changes in receptor levels, receptor desensitization, and locally produced oxytocin are factors that influence the effect of oxytocin on uterine contractility in labor. Activation of oxytocin receptor causes myometrial contractions by increasing intracellular Ca+2and production of prostaglandins. Since oxytocin induces contractions, the inhibition of its action has been a target in the management of preterm labor. Atosiban is today the only oxytocin receptor antagonist that is available as a tocolytic. However, the quest for oxytocin receptor antagonists with a better pharmacological profile has led to the synthesis of peptide and nonpeptide molecules such as barusiban, retosiban, L-368,899, and SSR-126768A. Many of these oxytocin receptor antagonists are used only as pharmacological tools, while others have tocolytic action. In this paper, we summarize the action of oxytocin and its receptor and we present an overview of the clinical and experimental data of oxytocin antagonists and their tocolytic action.
Some Additions to the Fuzzy Convergent and Fuzzy Bounded Sequence Spaces of Fuzzy Numbers
Authors: Şengönül M. , Zararsız Z.
Published: December 2011

Some properties of the fuzzy convergence and fuzzy boundedness of a sequence of fuzzy numbers were studied in Choi (1996). In this paper, we have consider, some important problems on these spaces and shown that these spaces are fuzzy complete module spaces. Also, the fuzzy α‐, fuzzy β‐, and fuzzy γ‐duals of the fuzzy module spaces of fuzzy numbers have been computeded, and some matrix transformations are given.
Is Farmland As Good As Gold?
Authors: Painter Marvin J.
Published: December 2011

An analysis of Canadian farmland risk and its return on investment shows that a Farmland Real Estate Investment Trust (F‐REIT) and gold would have significantly enhanced portfolio performance over the past 35 years. Investors who desire low‐risk portfolios would not have benefited from an F‐REIT or gold investment. However, investors in the medium‐risk category could have improved the financial performance of their portfolios by including an F‐REIT investment rather than gold. The financial gains from F‐REIT result from a level of risk that is lower than gold, REITs, and stocks, an expected yield that is greater than for bonds, and a low correlation with other financial asset returns.
Prevalence of Metabolic Syndrome Components in an Urban Mexican Sample: Comparison between Two Classifications
Authors: Isordia-Salas Irma , Santiago-Germán David , Rodrìguez-Navarro Helem , Almaráz-Delgado Martín , Leaños-Miranda Alfredo , Anaya-Gómez Francisco , Borrayo-Sánchez Gabriela , Majluf-Cruz Abraham
Published: December 2011

Background. The aim of this study was to examine the prevalence of metabolic syndrome (MS) components in an urban Mexican sample.Methods. A total of 854 subjects were included. Anthropometric, blood pressure measurements, clinical data, and overnight fasting blood samples were obtained from all subjects.Results. In accordance with definitions by the American Heart Association/ National Heart, Lung, and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF), the prevalence of MS among participants was 59.7 and 68.7%, respectively. The prevalence of MS was higher in women and in individuals older than 45 years of age. More than 40% of the subjects fulfilled four criterions of MS according to both definitions.Conclusions. There was a high prevalence of MS components in an urban Mexican sample. Therefore, strong strategies had to be developed for early detection of MS and its components to prevent DMT2 and atherothrombotic complications in these patients.
Lignosus rhinocerus(Cooke) Ryvarden: A Medicinal Mushroom That Stimulates Neurite Outgrowth in PC-12 Cells
Authors: Eik Lee-Fang , Naidu Murali , David Pamela , Wong Kah-Hui , Tan Yee-Shin , Sabaratnam Vikineswary
Published: December 2011

A national treasure mushroom,Lignosus rhinocerus, has been used to treat variety of ailments by local and indigenous communities in Malaysia. The aim of this study was to investigate the potential of the most valuable part ofL. rhinocerus, the sclerotium, on neurite outgrowth activity by using PC-12Adh cell line. Differentiated cells with one thin extension at least double the length of the cell diameter were scored positive. Our results showed that aqueous sclerotiumL. rhinocerusextract induced neurite outgrowths of 24.4% and 42.1% at 20 μg/mL (w/v) of aqueous extract alone and a combination of 20 μg/mL (w/v) aqueous extract and 30 ng/mL (w/v) of NGF, respectively. Combination of NGF and sclerotium extract had additive effects and enhanced neurite outgrowth. Neuronal differentiation was demonstrated by indirect immunofluorescence of neurofilament protein. Aqueous sclerotium extract contained neuroactive compounds that stimulated neurite outgrowthin vitro. To our knowledge this is the first report on neurite-stimulating activities ofL. rhinocerus.
Dual Mode Sensing with Low-Profile Piezoelectric Thin Wafer Sensors for Steel Bridge Crack Detection and Diagnosis
Authors: Yu Lingyu , Momeni Sepandarmaz , Godinez Valery , Giurgiutiu Victor , Ziehl Paul , Yu Jianguo
Published: December 2011

Monitoring of fatigue cracking in steel bridges is of high interest to many bridge owners and agencies. Due to the variety of deterioration sources and locations of bridge defects, there is currently no single method that can detect and address the potential sources globally. In this paper, we presented a dual mode sensing methodology integrating acoustic emission and ultrasonic wave inspection based on the use of low-profile piezoelectric wafer active sensors (PWAS). After introducing the research background and piezoelectric sensing principles, PWAS crack detection in passive acoustic emission mode is first presented. Their acoustic emission detection capability has been validated through both static and compact tension fatigue tests. With the use of coaxial cable wiring, PWAS AE signal quality has been improved. The active ultrasonic inspection is conducted by the damage index and wave imaging approach. The results in the paper show that such an integration of passive acoustic emission detection with active ultrasonic sensing is a technological leap forward from the current practice of periodic and subjective visual inspection and bridge management based primarily on history of past performance.
MBL Interferes with Endovascular Trophoblast Invasion in Pre-Eclampsia
Authors: Agostinis Chiara , Bossi Fleur , Masat Elisa , Radillo Oriano , Tonon Maddalena , De Seta Francesco , Tedesco Francesco , Bulla Roberta
Published: December 2011

The spiral arteries undergo physiologic changes during pregnancy, and the failure of this process may lead to a spectrum of pregnancy disorders, including pre-eclampsia. Our recent data indicate that decidual endothelial cells (DECs), covering the inner side of the spiral arteries, acquire the ability to synthesize C1q, which acts as a link between endovascular trophoblast and DECs favouring the process of vascular remodelling. In this study, we have shown that sera obtained from pre-eclamptic patients strongly inhibit the interaction between extravillous trophoblast (EVT) and DECs, preventing endovascular invasion of trophoblast cells. We further demonstrated that mannose-binding lectin (MBL), one of the factor increased in pre-eclamptic patient sera, strongly inhibits the interaction of EVT with C1q interfering with the process of EVT adhesion to and migration through DECs. These data suggest that the increased level of MBL in pre-eclampsia may contribute to the failure of the endovascular invasion of trophoblast cells.
Development of Murine Hepatic NK Cells during Ontogeny: Comparison with Spleen NK Cells
Authors: Wu Xian , Chen Yongyan , Wei Haiming , Sun Rui , Tian Zhigang
Published: December 2011

The phenotype of developing liver NK cells (CD3−NK1.1+) was investigated during mouse ontogeny comparing with spleen NK cells. The highest percentage of hepatic CD27−CD11b−NK cells occurred at the fetal stage. After birth, the percentage of CD27−CD11b−NK cells in both the liver and spleen gradually decreased to their lowest level at 6 weeks. More CD27+CD11b−NK cells were detected in the liver than that in spleen from week 1 to 6. Expression of NKG2A on liver NK cells was decreased but still much higher than that of spleen NK cells after 1 week. The NKG2D expression on liver NK cells increased to its highest level and was significantly higher than on spleen NK cells till 4 weeks. During mouse ontogeny, weaker expression of NKp46 and CD2 and stronger expression of CD69, CD11c, 2B4, and CD73 were observed on liver NK cells. Furthermore, neonatal liver NK cells express higher IFN-γ and perforin than adult .These results suggest that the maturation process of NK cells is unique in the livers, and liver microenvironments might play critical roles to keep NK cells in an immature status.
Current Status of the Immunomodulation and Immunomediated Therapeutic Strategies for Multiple Sclerosis
Authors: Chen Shyi-Jou , Wang Yen-Ling , Fan Hueng-Chuen , Lo Wen-Tsung , Wang Chih-Chien , Sytwu Huey-Kang
Published: December 2011

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and CD4+T cells form the core immunopathogenic cascade leading to chronic inflammation. Traditionally, Th1 cells (interferon-γ-producing CD4+T cells) driven by interleukin 12 (IL12) were considered to be the encephalitogenic T cells in MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Currently, Th17 cells (Il17-producing CD4+T cells) are considered to play a fundamental role in the immunopathogenesis of EAE. This paper highlights the growing evidence that Th17 cells play the core role in the complex adaptive immunity of EAE/MS and discusses the roles of the associated immune cells and cytokines. These constitute the modern immunological basis for the development of novel clinical and preclinical immunomodulatory therapies for MS discussed in this paper.
Methylated RASSF1a Is the First Specific DNA Marker for Minimal Residual Disease Testing in Neuroblastoma
Authors: Stutterheim Janine , Ichou Fatima Ait , den Ouden Emmy , Versteeg Rogier , Caron Huib N. , Tytgat Godelieve A.M. , van der Schoot C. Ellen
Published: December 2011

Purpose: PCR-based detection of minimal residual disease (MRD) in neuroblastoma (NB) is presently based on NB-specific transcripts. However, the expression of these targets varies between patients and upon treatment, and only PHOX2B is truly specific. RASSF1a is methylated (RASSF1aM) in NB, and we investigated whether it can serve as a specific and stable DNA MRD marker.

Patients and Methods: The RASSF1aM-specific quantitative real-time PCR was tested on control bone marrow (BM; n = 50), on 71 NB tumors, and on 159 clinical BM samples at diagnosis and at follow-up of 77 patients. Results were compared with a panel of RNA markers and correlated with prognosis.

Results: RASSF1aM was present in all stage 4 and 4s tumors (n = 50) and in 86% stages 1 to 3 tumors (n = 21). The level of methylation in stage 4 NB was correlated with overall survival (P = 0.02). RASSF1aM–PCR was highly specific (only 1 amplification in 50 control samples tested in triplicate) and had a similar sensitivity as the RNA-based PCRs, as shown on clinical samples. Moreover, RASSF1aM enabled accurate quantification without need for the original tumor.

Conclusions: RASSF1aM is a novel, highly specific DNA marker for MRD detection in NB, equal to PHOX2B in specificity and sensitivity, and better suitable for MRD quantification. We propose to include RASSF1aM in further prospective MRD studies in NB alongside RNA MRD markers. In addition, this assay might also be applicable for detection of circulating tumor cells in patients with other cancers withRASSF1aM such as breast or lung cancer. Clin Cancer Res; 18(3); 808–14. ©2011 AACR.
A Genome-Wide Association Study of Overall Survival in Pancreatic Cancer Patients Treated with Gemcitabine in CALGB 80303
Authors: Innocenti Federico , Owzar Kouros , Cox Nancy L. , Evans Patrick , Kubo Michiaki , Zembutsu Hitoshi , Jiang Chen , Hollis Donna , Mushiroda Taisei , Li Liang , Friedman Paula , Wang Liewei , Glubb Dylan , Hurwitz Herbert , Giacomini Kathleen M. , McLeod Howard L. , Goldberg Richard M. , Schilsky Richard L. , Kindler Hedy L. , Nakamura Yusuke , Ratain Mark J.
Published: December 2011

Background and Aims: Cancer and Leukemia Group B 80303 was a randomized, phase III study in patients with advanced pancreatic cancer treated with gemcitabine plus either bevacizumab or placebo. We prospectively collected germline DNA and conducted a genome-wide association study (GWAS) using overall survival (OS) as the endpoint.

Experimental Design: DNA from 351 patients was genotyped for more than 550,000 single-nucleotide polymorphisms (SNP). Associations between OS and SNPs were investigated using the log-linear 2-way multiplicative Cox proportional hazards model. The subset of 294 genetically European patients was used for the primary analysis.

Results: A nonsynonymous SNP in interleukin (IL)17F (rs763780, H161R) and an intronic SNP in strong linkage disequilibrium (rs7771466) were associated with OS using genome-wide criteria (P ≤ 10−7). Median OS was significantly shorter (P = 2.61 × 10−8) for the rs763780 heterozygotes [3.1 months; 95% confidence interval (CI), 2.3–4.3] than for the patients without this variant (6.8 months; 95% CI, 5.8–7.3). After adjustment by stratification factors, the P value for the association was 9.51 × 10−7.

Conclusions: The variant 161R form of IL-17F is a natural antagonist of the antiangiogenic effects of wild-type 161H IL-17F, and angiogenesis may play an important role in the metastatic spread of pancreatic cancer. In this preliminary study, we hypothesize that the angiogenetic potential of pancreatic cancers in patients with variant IL-17F is higher than that of tumors in patients with wild-type IL-17F, conferring worse prognosis. This exploratory GWAS may provide the foundation for testing the biology and clinical effects of novel genes and their heritable variants through mechanistic and confirmatory studies in pancreatic cancer. Clin Cancer Res; 18(2); 577–84. ©2011 AACR.
Does Hypereosinophilic Syndrome Precede Common B Acute Lymphoblastic Leukaemia in Childhood? A Case Report
Authors: Ayhan Aylin Canbolat , Timur Cetin , Ayhan Yusuf , Cakır Betul , Erguven Muferet
Published: December 2011

Hypereosinophilic syndrome (HES) and the association of hypereosinophilia with acute lymphoblastic leukaemia (ALL) are both rare in children. Some acute myelogenous leukaemias can present with eosinophilia, but the relationship between HES and ALL is not well known and is rarer than the relationship between HES and acute myelogenous leukaemia. Patients are diagnosed with HES when no cause is found to explain the eosinophilia leading to end organ damage. For this reason, it is recommended that patients presenting with hypereosinophilia be carefully assessed to exclude any malignant clonal proliferation. HES may present with severe clinical manifestations such as high leucocyte count, anaemia, thrombocytopaenia, hepatosplenomegaly or cardiac and neurological involvement, all of which are primarily features of myeloproliferative disorders. Some patients with HES can develop chronic eosinophilic leukaemia. Successful treatment of HES with agents used in chronic myeloid leukaemia supports the idea that HES can be a chronic myeloid disorder. There are few cases reporting an association between ALL and hypereosinophilia that precedes or is concomitant with ALL. Here we report the case of a 14-year-old girl who developed common B ALL 7 months after diagnosis and treatment of HES. Interestingly, eosinophilia was not concomitant with the diagnosis of ALL.
Migraine Mutations Increase Stroke Vulnerability by Facilitating Ischemic Depolarizations
Authors: Eikermann-Haerter Katharina , Hyun Lee Jeong , Yuzawa Izumi , Liu Christina H. , Zhou Zhipeng , Kyoung Shin Hwa , Zheng Yi , Qin Tao , Kurth Tobias , Waeber Christian , Ferrari Michel D. , van den Maagdenberg Arn M.J.M. , Moskowitz Michael A. , Ayata Cenk
Published: December 2011

Background—

Migraine is an independent risk factor for stroke. Mechanisms underlying this association are unclear. Familial hemiplegic migraine (FHM), a migraine subtype that also carries an increased stroke risk, is a useful model for common migraine phenotypes because of shared aura and headache features, trigger factors, and underlying glutamatergic mechanisms.

Methods and Results—

Here, we show that FHM type 1 (FHM1) mutations in Ca
V
2.1 voltage-gated Ca
2+
channels render the brain more vulnerable to ischemic stroke. Compared with wild-type mice, 2 FHM1 mutant mouse strains developed earlier onset of anoxic depolarization and more frequent peri-infarct depolarizations associated with rapid expansion of infarct core on diffusion-weighted magnetic resonance imaging and larger perfusion deficits on laser speckle flowmetry. Cerebral blood flow required for tissue survival was higher in the mutants, leading to infarction with milder ischemia. As a result, mutants developed larger infarcts and worse neurological outcomes after stroke, which were selectively attenuated by a glutamate receptor antagonist.

Conclusions—

We propose that enhanced susceptibility to ischemic depolarizations akin to spreading depression predisposes migraineurs to infarction during mild ischemic events, thereby increasing the stroke risk.
Extramedullary Hematopoiesis Generates Ly-6C
high
Monocytes That Infiltrate Atherosclerotic Lesions
Authors: Robbins Clinton S. , Chudnovskiy Aleksey , Rauch Philipp J. , Figueiredo Jose-Luiz , Iwamoto Yoshiko , Gorbatov Rostic , Etzrodt Martin , Weber Georg F. , Ueno Takuya , van Rooijen Nico , Mulligan-Kehoe Mary Jo , Libby Peter , Nahrendorf Matthias , Pittet Mikael J. , Weissleder Ralph , Swirski Filip K.
Published: December 2011

Background—

Atherosclerotic lesions are believed to grow via the recruitment of bone marrow–derived monocytes. Among the known murine monocyte subsets, Ly-6C
high
monocytes are inflammatory, accumulate in lesions preferentially, and differentiate. Here, we hypothesized that the bone marrow outsources the production of Ly-6C
high
monocytes during atherosclerosis.

Methods and Results—

Using murine models of atherosclerosis and fate-mapping approaches, we show that hematopoietic stem and progenitor cells progressively relocate from the bone marrow to the splenic red pulp, where they encounter granulocyte macrophage colony-stimulating factor and interleukin-3, clonally expand, and differentiate to Ly-6C
high
monocytes. Monocytes born in such extramedullary niches intravasate, circulate, and accumulate abundantly in atheromata. On lesional infiltration, Ly-6C
high
monocytes secrete inflammatory cytokines, reactive oxygen species, and proteases. Eventually, they ingest lipids and become foam cells.

Conclusions—

Our findings indicate that extramedullary sites supplement the hematopoietic function of the bone marrow by producing circulating inflammatory cells that infiltrate atherosclerotic lesions.