bluuebunny/crossref_metadata_2025 huggingface dataset:
A time-aware type system for data-race protection and guaranteed initialization
Authors: Matsakis Nicholas D. , Gross Thomas R.
Published: February 2011

We introduce a type system based on intervals, objects representing the time in which a block of code will execute. The type system can verify time-based properties such as when a field will be accessed or a method will be invoked.

One concrete application of our type system is data-race protection: For fields which are initialized during one phase of the program and constant thereafter, users can designate the interval during which the field is mutable. Code which happens after this initialization interval can safely read the field in parallel. We also support fields guarded by a lock and even the use of dynamic race detectors.

Another use for intervals is to designate different phases in the object's lifetime, such as a constructor phase. The type system then ensures that only appropriate methods are invoked in each phase.
Automatic atomic region identification in shared memory SPMD programs
Authors: Upadhyaya Gautam , Midkiff Samuel P. , Pai Vijay S.
Published: February 2011

This paper presents
TransFinder
, a compile-time tool that automatically determines which statements of an unsynchronized multithreaded program must be enclosed in atomic regions to enforce
conflict-serializability
. Unlike previous tools, TransFinder requires no programmer input (beyond the program) and is more efficient in both time and space.

Our implementation shows that the generated atomic regions range from being identical to, or smaller than, the programmer-specified transactions in the three Java Grande benchmarks considered, and in five of the eight STAMP benchmarks considered, while still providing identical synchronization semantics and results. The generated atomic regions are between 5 and 38 lines larger in the three remaining STAMP benchmarks. In the most conservative case, TransFinder can, based on the program structure, successfully identify and suggest an alternative that conforms exactly to the programmer-specified atomic regions. By generating small, highly-targeted, conflict-serializable atomic regions, TransFinder allows the programmer to focus further tuning efforts on only a small portion of the code (when further tuning is needed).
Task types for pervasive atomicity
Authors: Kulkarni Aditya , Liu Yu David , Smith Scott F.
Published: February 2011

Atomic regions are an important concept in correct concurrent programming: since atomic regions can be viewed as having executed in a single step, atomicity greatly reduces the number of possible interleavings the programmer needs to consider. This paper describes a method for building atomicity into a programming language in an organic fashion. We take the view that atomicity holds for whole threads by default, and a division into smaller atomic regions occurs only at points where an explicit need for sharing is needed and declared. A corollary of this view is every line of code is part of some atomic region. We define a polymorphic type system,
Task Types
, to enforce most of the desired atomicity properties statically. We show the reasonableness of our type system by proving that type soundness, isolation invariance, and atomicity enforcement properties hold at run time. We also present initial results of a Task Types implementation built on Java
Concurrent programming with revisions and isolation types
Authors: Burckhardt Sebastian , Baldassin Alexandro , Leijen Daan
Published: February 2011

Building applications that are responsive and can exploit parallel hardware while remaining simple to write, understand, test, and maintain, poses an important challenge for developers. In particular, it is often desirable to enable various tasks to read or modify shared data concurrently without requiring complicated locking schemes that may throttle concurrency and introduce bugs.

We introduce a mechanism that simplifies the parallel execution of different application tasks. Programmers declare what data they wish to share between tasks by using
isolation
types, and execute tasks concurrently by forking and joining
revisions
. These revisions are isolated: they read and modify their own private copy of the shared data only. A runtime creates and merges copies automatically, and resolves conflicts deterministically, in a manner declared by the chosen isolation type.

To demonstrate the practical viability of our approach, we developed an efficient algorithm and an implementation in the form of a C# library, and used it to parallelize an interactive game application. Our results show that the parallelized game, while simple and very similar to the original sequential game, achieves satisfactory speedups on a multicore processor.
SPUR
Authors: Bebenita Michael , Brandner Florian , Fahndrich Manuel , Logozzo Francesco , Schulte Wolfram , Tillmann Nikolai , Venter Herman
Published: February 2011

Tracing just-in-time compilers (TJITs) determine frequently executed traces (hot paths and loops) in running programs and focus their optimization effort by emitting optimized machine code specialized to these traces. Prior work has established this strategy to be especially beneficial for dynamic languages such as JavaScript, where the TJIT interfaces with the interpreter and produces machine code from the JavaScript trace.

This direct coupling with a JavaScript interpreter makes it difficult to harness the power of a TJIT for other components that are not written in JavaScript, e.g., the DOM implementation or the layout engine inside a browser. Furthermore, if a TJIT is tied to a particular high-level language interpreter, it is difficult to reuse it for other input languages as the optimizations are likely targeted at specific idioms of the source language.

To address these issues, we designed and implemented a TJIT for Microsoft's Common Intermediate Language CIL (the target language of C#, VisualBasic, F#, and many other languages). Working on CIL enables TJIT optimizations for any program compiled to this platform. In addition, to validate that the performance gains of a TJIT for JavaScript do not depend on specific idioms of JavaScript that are lost in the translation to CIL, we provide a performance evaluation of our JavaScript runtime which translates JavaScript to CIL and then runs on top of our CIL TJIT.
Patterns and statistical analysis for understanding reduced resource computing
Authors: Rinard Martin , Hoffmann Henry , Misailovic Sasa , Sidiroglou Stelios
Published: February 2011

We present several general, broadly applicable mechanisms that enable computations to execute with reduced resources, typically at the cost of some loss in the accuracy of the result they produce.We identify several general computational patterns that interact well with these resource reduction mechanisms, present a concrete manifestation of these patterns in the form of simple model programs, perform simulationbased explorations of the quantitative consequences of applying these mechanisms to our model programs, and relate the model computations (and their interaction with the resource reduction mechanisms) to more complex benchmark applications drawn from a variety of fields.
Language virtualization for heterogeneous parallel computing
Authors: Chafi Hassan , DeVito Zach , Moors Adriaan , Rompf Tiark , Sujeeth Arvind K. , Hanrahan Pat , Odersky Martin , Olukotun Kunle
Published: February 2011

As heterogeneous parallel systems become dominant, application developers are being forced to turn to an incompatiblemix of low level programming models (e.g. OpenMP, MPI, CUDA, OpenCL). However, these models do little to shield developers from the difficult problems of parallelization, data decomposition and machine-specific details. Most programmersare having a difficult time using these programming models effectively. To provide a programming modelthat addresses the productivity and performance requirements for the average programmer, we explore a domainspecificapproach to heterogeneous parallel programming.

We propose language virtualization as a new principle that enables the construction of highly efficient parallel domain specific languages that are embedded in a common host language. We define criteria for language virtualization and present techniques to achieve them.We present two concrete case studies of domain-specific languages that are implemented using our virtualization approach.
Flexible modeling tools for pre-requirements analysis
Authors: Ossher Harold , Bellamy Rachel , Simmonds Ian , Amid David , Anaby-Tavor Ateret , Callery Matthew , Desmond Michael , de Vries Jacqueline , Fisher Amit , Krasikov Sophia
Published: February 2011

A serious tool gap exists at the start of the software lifecy-cle, before requirements formulation. Pre-requirements analysts gather information, organize it to gain insight, en-vision possible futures, and present insights and recom-mendations to stakeholders. They typically use office tools, which give great freedom, but no help with consistency management, change propagation, or information migration to downstream tools. Despite these downsides, office tools are still favored over modeling tools, which are constrain-ing and difficult to use. We introduce the notion of flexible modeling tools, which blend the advantages of office and modeling tools. We propose a conceptual architecture for such tools, and outline research challenges to be met in realizing them. We briefly describe the Business Insight Toolkit, a prototype tool embodying this architecture.
Managing ambiguity in programming by finding unambiguous examples
Authors: Arnold Kenneth C. , Lieberman Henry
Published: February 2011

We propose a new way to raise the level of discourse in the programming process: permit ambiguity, but manage it by linking it to unambiguous examples. This allows programming environments to work with informal descriptions that lack precise semantics, such as natural language descriptions or conceptual diagrams, without requiring programmers to formulate their ideas in a formal language first. As an example of this idea, we present Zones, a code search and reuse interface that connects code with ambiguous natural language statements about its purpose. The backend, called ProcedureSpace, relates purpose statements, static code analysis features, and natural language background knowledge. ProcedureSpace can search for code given statements of purpose or vice versa, and can find code that was never annotated or commented. Since completed Zones searches become annotations, system coverage grows with user interaction. Users in a preliminary study found that reasoning jointly over natural language and programming language helped them reuse code.
Faith, hope, and love
Authors: Hanenberg Stefan
Published: February 2011

Research in the area of programming languages has different facets -- from formal reasoning about new programming language constructs (such as type soundness proofs for new type systems) over inventions of new abstractions, up to performance measurements of virtual machines. A closer look into the underlying research methods reveals a distressing characteristic of programming language research: developers, which are the main audience for new language constructs, are hardly considered in the research process. As a consequence, it is simply not possible to state whether a new construct that requires some kind of interaction with the developer has any positive impact on the construction of software. This paper argues for appropriate research methods in programming language research that rely on studies of developers -- and argues that the introduction of corresponding empirical methods not only requires a new understanding of research but also a different view on how to teach software science to students.
The Tower of Babel did not fail
Authors: Adamczyk Paul , Hafiz Munawar
Published: February 2011

Fred Brooks' retelling of the biblical story of the Tower of Babel offers many insights into what makes building software difficult. The difficulty, according to common interpretations, comes from the communication and organizational problems in software development. But the story contains one more important lesson that people tend to miss: one cannot accomplish
impossible
goals, which programmers are often asked to do. Software engineering, as a discipline, can overcome poor communication; but as long as we attempt to live up to impossible expectations, we will always fail.
The case for evolvable software
Authors: Forrest Stephanie
Published: February 2011

As programmers, we like to think of software as the product of our intelligent design, carefully crafted to meet well-specified goals. In reality, software evolves inadvertently through the actions of many individual programmers, often leading to unanticipated consequences. Large complex software systems are subject to constraints similar to those faced by evolving biological systems, and we have much to gain by viewing software through the lens of evolutionary biology. The talk will highlight recent research that applies the mechanisms of evolution quite directly to the problem of repairing software bugs.
Art, science, and fear
Authors: Pierce Benjamin C.
Published: February 2011

Scientists and artists share a conviction that key elements of their work-creativity, craft, analysis, intuition--are somehow deeply similar. Most Onward! participants will have a clear sense of the scientific variants of these qualities, and of what it takes to manifest them in our day-to-day work as researchers and software designers. This talk looks at how ideas are developed and refined in the making of visual art, how the same qualities--especially creativity, the most ineffable--come into play, and how artists and scientists grapple with the various fears that beset creative work.
To achieve our highest goals, we must be willing to abandon them
Authors: Stanley Kenneth O.
Published: February 2011

Someday computer scientists may build systems of astronomical complexity that provide profound benefit to humanity. However, the question today is how such feats will ultimately be achieved. As is common with technology, present limitations to modern approaches challenge our imagination to search for new paradigms and organizing principles. To examine the prerequisites to achieving our most ambitious objectives, this talk will contemplate the implications of recent counterintuitive results from experiments with evolutionary algorithms that suggest that search (which is a metaphor for innovation in general) is sometimes most effective when it is not explicitly seeking an objective. In particular, through several experiments in interactive evolution and with an algorithm called "novelty search," a picture of innovation is emerging in which objectives can help to guide us one stepping-stone away from our present understanding, yet ultimately become handcuffs that also blind us to essential orthogonal discoveries on the road to long-term innovation. While the implications of these insights for reaching our highest goals are in part sobering, the silver lining is that much can be gained by liberating ourselves from the temptation to frame all our projects in terms of what they ultimately aim to achieve. Instead, with evidence in hand, we can exploit the structure of the unknown by orienting ourselves towards discovery and away from the shackles of mandated outcomes.
Diminished glucagon suppression after β-cell reduction is due to impaired α-cell function rather than an expansion of α-cell mass
Authors: Meier Juris J. , Ueberberg Sandra , Korbas Simone , Schneider Stephan
Published: February 2011

Impaired suppression of glucagon levels after oral glucose or meal ingestion is a hallmark of type 2 diabetes. Whether hyperglucagonemia after a β-cell loss results from a functional upregulation of glucagon secretion or an increase in α-cell mass is yet unclear. CD-1 mice were treated with streptozotocin (STZ) or saline. Pancreatic tissue was collected after 14, 21, and 28 days and examined for α- and β-cell mass and turnover. Intraperitoneal (ip) glucose tolerance tests were performed at day 28 as well as after 12 days of subcutaneous insulin treatment, and glucose, insulin, and glucagon levels were determined. STZ treatment led to fasting and post-challenge hyperglycemia ( P < 0.001 vs. controls). Insulin levels increased after glucose injection in controls ( P < 0.001) but were unchanged in STZ mice ( P = 0.36). Intraperitoneal glucose elicited a 63.1 ± 4.1% glucagon suppression in control mice ( P < 0.001), whereas the glucagon suppression was absent in STZ mice ( P = 0.47). Insulin treatment failed to normalize glucagon levels. There was a significant inverse association between insulin and glucagon levels after ip glucose ingestion ( r2 = 0.99). β-Cell mass was reduced by ∼75% in STZ mice compared with controls ( P < 0.001), whereas α-cell mass remained unchanged ( P > 0.05). α-Cell apoptosis (TUNEL) and replication (Ki67) were rather infrequently noticed, with no significant differences between the groups. These studies underline the importance of endogenous insulin for the glucose-induced suppression of glucagon secretion and suggest that the insufficient decline in glucagon levels after glucose administration in diabetes is primarily due to a functional loss of intraislet inhibition of α-cell function rather than an expansion of α-cell mass.
Increased muscular dehydroepiandrosterone levels are associated with improved hyperglycemia in obese rats
Authors: Sato Koji , Iemitsu Motoyuki , Aizawa Katsuji , Mesaki Noboru , Fujita Satoshi
Published: February 2011

This study was undertaken to assess the effects of dehydroepiandrosterone (DHEA) administration and exercise training on muscular DHEA and 5α-dihydrotestosterone (DHT) levels and hyperglycemia in diet-induced obese and hyperglycemic rats. After 14 wk of a high-sucrose diet, obese male Wistar rats were assigned randomly to one of three 6-wk regimens: control, DHEA treatment, or exercise training (running at 25 m/min for 1 h, 5 days/wk; n = 10 each group). Results indicate that either 6 wk of DHEA treatment or exercise training significantly attenuated serum insulin and fasting glucose levels compared with the control group. Plasma and muscle concentrations of DHEA and DHT and expression levels of 5α-reductase were significantly higher in the DHEA-treated and exercise-training groups. Moreover, both DHEA administration and exercise training upregulated GLUT4 translocation with concomitant increases in protein kinase B and protein kinase Cζ/λ phosphorylation. Muscle DHEA and DHT concentrations closely correlated with blood glucose levels (DHEA treatment: r = −0.68, P < 0.001; exercise training: r = −0.65, P < 0.001), serum insulin levels, and activation of the GLUT4-regulated signaling pathway. Thus, increased levels of muscle sex steroids may contribute to improved fasting glucose levels via upregulation of GLUT4-regulated signaling in diet-induced obesity and hyperglycemia.
Outgrowth of Drug-Resistant Carcinomas Expressing Markers of Tumor Aggression after Long-term TβRI/II Kinase Inhibition with LY2109761
Authors: Connolly Erin C. , Saunier Elise F. , Quigley David , Luu Minh Thu , De Sapio Angela , Hann Byron , Yingling Jonathan M. , Akhurst Rosemary J.
Published: February 2011

TGF-β is produced excessively by many solid tumors and can drive malignant progression through multiple effects on the tumor cell and microenvironment. TGF-β signaling pathway inhibitors have shown efficacy in preclinical models of metastatic cancer. Here, we investigated the effect of systemic LY2109761, a TGF-β type I/II receptor (TβRI/TβRII) kinase inhibitor, in both a tumor allograft model and the mouse skin model of de novo chemically induced carcinogenesis in vivo. Systemic LY2109761 administration disrupted tumor vascular architecture and reduced myofibroblast differentiation of E4 skin carcinoma cells in a tumor allograft. In the 7,12-dimethyl-benzanthracene plus phorbol myristate acetate–induced skin chemical carcinogenesis model, acute dosing of established naive primary carcinomas with LY2109761 (100 mg/kg) every 8 hours for 10 days (100 mg/kg) diminished phospho-Smad2 (P-Smad2) levels and marginally decreased the expression of inflammatory and invasive markers. Sustained exposure to LY2109761 (100 mg/kg/d) throughout the tumor outgrowth phase had no effect on carcinoma latency or incidence. However, molecular analysis of resultant carcinomas by microarray gene expression, Western blotting, and immunohistochemistry suggests that long-term LY2109761 exposure leads to the outgrowth of carcinomas with elevated P-Smad2 levels that do not respond to drug. This is the first description of acquired resistance to a small-molecule inhibitor of the TβRI/TβRII kinase. Resultant carcinomas were more aggressive and inflammatory in nature, with delocalized E-cadherin and elevated expression of Il23a, laminin V, and matrix metalloproteinases. Therefore, TGF-β inhibitors might be clinically useful for applications requiring acute administration, but long-term patient exposure to such drugs should be undertaken with caution. Cancer Res; 71(6); 2339–49. ©2011 AACR.
Novel Functions for mda-7/IL-24 and IL-24 delE5: Regulation of Differentiation of Acute Myeloid Leukemic Cells
Authors: Yang Bin-Xia , Duan Yong-Juan , Dong Cheng-Ya , Zhang Fang , Gao Wei-Feng , Cui Xue-Ying , Lin Yong-Min , Ma Xiao-Tong
Published: February 2011

Characterizing genes associated with leukemic cell differentiation may provide help for understanding mechanisms on the leukemia differentiation. The aim of this study is to investigate whether the expression of melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) could be induced during leukemia differentiation and whether mda-7/IL-24 plays a role in leukemia differentiation. We showed that the expression of mda-7/IL-24 and IL-24 delE5, an mda-7/IL-24 splice variant, was induced in U937 and HL60 cells during 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated monocytic differentiation. Activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway was required for their induction. Knockdown of mda-7/IL-24 and IL-24 delE5 resulted in significant inhibition of the monocytic differentiation induced by TPA. More importantly, ectopic overexpression of mda-7/IL-24 and IL-24 delE5 significantly induced U937 cells, HL60 cells, and blast cells from patients with acute myeloid leukemia–M5 to differentiate, whereas normal hematopoietic progenitors were not affected. Furthermore, the molecular effector associated with selective differentiation induction by mda-7/IL-24 and IL-24 delE5 may be reactive oxygen species (ROS), and the source of ROS generation was nicotinamide adenine dinucleotide phosphate oxidase. Taken together, our results reveal the mechanism by which TPA induces monocytic differentiation and show for the first time the specific differentiation-inducing effects of mda-7/IL-24 and IL-24 delE5 on human myeloid leukemic cells. Mol Cancer Ther; 10(4); 615–25. ©2011 AACR.
Subcutaneous Immunotherapy with a Depigmented Polymerized Birch Pollen Extract – A New Therapeutic Option for Patients with Atopic Dermatitis
Authors: Novak Natalija , Thaci Diamant , Hoffmann Matthias , Fölster-Holst Regina , Biedermann Thilo , Homey Bernhard , Schaekel Knut , Stefan Josef A. , Werfel Thomas , Bieber Thomas , Sager Angelika , Zuberbier Torsten
Published: February 2011

Background: Birch pollen is an important outdoor allergen able to aggravate symptoms in atopic dermatitis (AD). Specific immunotherapy (SIT), an established procedure for allergic airway diseases, might also represent an attractive therapeutic option for the causal treatment of allergen-triggered cutaneous symptoms in these patients. Studies with house dust mite SIT have already shown beneficial effects in AD patients, whereas the safety and efficacy of SIT with birch pollen extract in AD patients have not been studied so far. The aim of this study was to evaluate for the first time the safety and efficacy of SIT with a depigmented polymerized birch pollen extract in AD patients. Methods: Fifty-five adult patients with moderate-to-severe AD and clinically relevant sensitization to birch pollen received SIT for 12 weeks. SIT was continued during birch pollen season. The assessment of safety, the total SCORAD value, and the Dermatology Life Quality Index (DLQI) were evaluated. Results: The median total SCORAD value was reduced by 34% (p < 0.001) during the course of treatment and the mean DLQI improved by 49% (p < 0.001) despite strong simultaneous birch pollen exposure. Eight patients (14.5%) developed systemic reactions and 19 patients (34.5%) developed local reactions which were of mild intensity in most cases. No patient discontinued the study prematurely due to adverse drug reactions. Coseasonal treatment was well tolerated. Conclusion: SIT with a depigmented polymerized birch pollen extract leads to significant improvement of the SCORAD value and the DLQI in patients suffering from moderate-to-severe AD sensitized to birch pollen.
The Roles of B Cells and Their Interactions with Fibroblast-Like Synoviocytes in the Pathogenesis of Rheumatoid Arthritis
Authors: Wang Qingtong , Ma Yukun , Liu Dandan , Zhang Lingling , Wei Wei
Published: February 2011

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs but principally attacks synovial joints. The pathogenesis of RA is complex and encompasses many cell types, including T cells, B cells and fibroblast-like synoviocytes (FLSs); each is believed to play a significant role in the process of RA. Interactions between T cells and B cells and between T cells and FLSs have been studied in depth. However, it has been showed that B cells also play a critical role in rheumatoid synovitis. Therefore, cell-cell contact between B cells and FLSs may be significant in the pathophysiology of RA. This review focuses on recent advances in the research of the interaction between B cells and FLSs. Considering this interaction may provide directions for innovations in RA therapy.
In vitro Biotransformation, in vivo Efficacy and Pharmacokinetics of Antimalarial Chalcones
Authors: Gutteridge Clare E. , Thota Darshan S. , Curtis Sean M. , Kozar Michael P. , Li Qigui , Xie Lisa , Zhang Jing , Melendez Victor , Asher Constance O. , Luong Thulan T. , Gerena Lucia , Nichols Daniel A. , Montip Gettayacamin
Published: February 2011

4′-n-Butoxy-2,4-dimethoxy-chalcone (MBC) has been described as protecting mice from an otherwise lethal infection with Plasmodium yoelii when dosed orally at 50 mg/kg/dose, daily for 5 days. In contrast, we found that oral dosing of MBC at 640 mg/kg/dose, daily for 5 days, failed to extend the survivability of P. berghei-infected mice. The timing of compound administration and metabolic activation likely contribute to the outcome of efficacy testing in vivo. Microsomal digest of MBC yielded 4′-n-butoxy-4-hydroxy-2-methoxy-chalcone and 4′-(1-hydroxy-n-butoxy)-2,4-dimethoxy-chalcone. We propose that the latter will hydrolyze in vivo to 4′-hydroxy-2,4-dimethoxy-chalcone, which has greater efficacy than MBC in our P. berghei-infected mouse model and was detected in plasma following oral dosing of mice with MBC. Pharmacokinetic parameters suggest that poor absorption, distribution, metabolism and excretion properties contribute to the limited in vivoefficacy observed for MBC and its analogs.
Long-Term Surgical and Hardware-Related Complications of Deep Brain Stimulation
Authors: Doshi Paresh K.
Published: February 2011

Objective: To evaluate the incidence of surgical and hardware-associated complications of deep brain stimulation (DBS) for a range of movement disorders. Methods: The study design is a retrospective analysis and review of surgical and hardware complications of DBS performed by a single surgeon from 1999 to 2009. A total of 153 cases of DBS (298 electrodes) for various movement disorders and a minimum follow-up of 1 year have been included. Two patients could not be implanted. A further 54 patients who underwent change of the implantable pulse generator (IPG) have been included for analysis of hardware-related complications. Results: The mean follow-up was 64 ± 36.15 (range = 12–129) months for the DBS group. Twenty-four (15.6%) patients developed complications. Confusion occurred in 3.9%, vasovagal attack in 1.9%, lead migration/misplaced lead in 2.5%, erosion and infection in 4.5% and IPG malfunction occurred in 1.4% of the patients. When calculated with respect to the number of electrodes and IPG replacements, the complication rate was lower (11.9%). Three patients had their system explanted, two of them being patients with dystonia who had inadvertently damaged their operative site. Conclusion: DBS surgery is a relatively safe surgery, with most of the complications being minor, without long-term morbidity. The complication rate in elderly (age ≧65 years) is comparable to that in younger patients. However, confusion is more frequent in this age group, and patients and relatives can be prepared to accept this as a transient morbidity.
Augmented Expression and Activity of Extracellular Matrix-Degrading Enzymes in Regions of Low Endothelial Shear Stress Colocalize With Coronary Atheromata With Thin Fibrous Caps in Pigs
Authors: Chatzizisis Yiannis S. , Baker Aaron B. , Sukhova Galina K. , Koskinas Konstantinos C. , Papafaklis Michail I. , Beigel Roy , Jonas Michael , Coskun Ahmet U. , Stone Benjamin V. , Maynard Charles , Shi Guo-Ping , Libby Peter , Feldman Charles L. , Edelman Elazer R. , Stone Peter H.
Published: February 2011

Background—

The molecular mechanisms that determine the localized formation of thin-capped atheromata in the coronary arteries remain unknown. This study tested the hypothesis that low endothelial shear stress augments the expression of matrix-degrading proteases and thereby promotes the formation of thin-capped atheromata.

Methods and Results—

Intravascular ultrasound–based, geometrically correct 3-dimensional reconstruction of the coronary arteries of 12 swine was performed in vivo 23 weeks after initiation of diabetes mellitus and a hyperlipidemic diet. Local endothelial shear stress was calculated in plaque-free subsegments of interest (n=142) with computational fluid dynamics. At week 30, the coronary arteries (n=31) were harvested and the same subsegments were identified. The messenger RNA and protein expression and elastolytic activity of selected elastases and their endogenous inhibitors were assessed. Subsegments with low preceding endothelial shear stress at week 23 showed reduced endothelial coverage, enhanced lipid accumulation, and intense infiltration of activated inflammatory cells at week 30. These lesions showed increased expression of messenger RNAs encoding matrix metalloproteinase-2, -9, and -12, and cathepsins K and S relative to their endogenous inhibitors and increased elastolytic activity. Expression of these enzymes correlated positively with the severity of internal elastic lamina fragmentation. Thin-capped atheromata developed in regions with lower preceding endothelial shear stress and had reduced endothelial coverage, intense lipid and inflammatory cell accumulation, enhanced messenger RNA expression and elastolytic activity of MMPs and cathepsins, and severe internal elastic lamina fragmentation.

Conclusions—

Low endothelial shear stress induces endothelial discontinuity and accumulation of activated inflammatory cells, thereby augmenting the expression and activity of elastases in the intima and shifting the balance with their inhibitors toward matrix breakdown. Our results provide new insight into the mechanisms of regional formation of plaques with thin fibrous caps.
Stimulation of Renin Secretion by Catecholamines Is Dependent on Adenylyl Cyclases 5 and 6
Authors: Aldehni Fadi , Tang Tong , Madsen Kirsten , Plattner Michael , Schreiber Andrea , Friis Ulla G. , Hammond H. Kirk , Han Pyung Lim , Schweda Frank
Published: February 2011

The sympathetic nervous system stimulates renin release from juxtaglomerular cells via the β-adrenoreceptor-cAMP pathway. Recent in vitro studies have suggested that the calcium-inhibited adenylyl cyclases (ACs) 5 and 6 possess key roles in the control of renin exocytosis. To investigate the relative contribution of AC5 and AC6 to the regulation of renin release in vivo we performed experiments using AC5 and AC6 knockout mice. Male AC5
−/−
mice exhibited normal plasma renin concentrations, renal renin synthesis (mRNA and renin content), urinary volume, and systolic blood pressure. In male AC6
−/−
mice, plasma renin concentration (AC6
−/−
: 732±119; AC6
+/+
: 436±78 ng of angiotensin I per hour*mL
−1
;
P
<0.05), and renin synthesis were stimulated associated with an increased excretion of dilute urine (1.55-fold;
P
<0.05) and reduced blood pressure (−10.6 mm Hg;
P
<0.001). Stimulation of plasma renin concentration by a single injection of the β-adrenoreceptor agonist isoproterenol (10 mg/kg IP) was significantly attenuated in AC5
−/−
(male: −20%; female: −33%) compared with wild-type mice in vivo. The mitigation of the plasma renin concentration response to isoproterenol was even more pronounced in AC6
−/−
(male: −63%; female: −50% versus AC6
+/+
). Similarly, the effects of isoproterenol, prostaglandin E2, and pituitary adenylyl cyclase-activating polypeptide on renin release from isolated perfused kidneys were attenuated to a higher extent in AC6
−/−
(−51% to −98% versus AC6
+/+
) than in AC5
−/−
(−31% to 46% versus AC5
+/+
). In conclusion, both AC5 and AC6 are involved in the stimulation of renin secretion in vivo, and AC6 is the dominant isoforms in this process.
Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon
Authors: Mohino E. , Rodríguez-Fonseca B. , Mechoso C. R. , Gervois S. , Ruti P. , Chauvin F.
Published: February 2011

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.
World Overview and European Sovereign Debt
Authors: Holland Dawn , Barrell Ray , Delannoy Aurélie , Fic Tatiana , Hurst Ian , Orazgani Ali , Paluchowski Paweł
Published: February 2011

Short-tem inflationary pressures have risen on a global scale in recent months and, given the source of the impulse is commodity markets, this dampens the prospects for growth in 2011 in most countries. Global food prices have been under pressure since July 2010, reflecting poor harvests in many parts of the world. Metals prices have also risen rapidly, while non-food agricultural price inflation accelerated towards the end of the year. We expect average food and other agricultural prices in 2011 to be more than 25 per cent higher than they were in 2010, while metals prices are expected to be more than 30 per cent above last year's average level, as shown in figure 1. The price of oil exhibited moderate inflation through September 2010, but rose sharply in the final quarter of the year. The rise in the price of oil may be a reflection of demand pressures from countries such as China and India, as well as the recovery in demand from advanced economies, while the weakness of the US dollar and an expected tightening of regulation following recent oil spills may also be adding to price pressures. The price of Brent crude currently stands at over $98 per barrel, roughly $19 per barrel higher than was priced into futures markets three months ago. Barrell, Delannoy and Holland discuss the macroeconomic implications of the recent rise in the oil price elsewhere in this Review. If sustained we expect this to reduce growth in the OECD by about ½ per cent this year. The impact on oil-intensive emerging economies such as China and India may be slightly greater, while oil exporters gain from the high price.
As Higher Education Expands, is it Contributing to Greater Inequality?
Authors: Carnoy Martin
Published: February 2011

This paper reviews the various elements that enter into the relation between higher education expansion and income distribution. Contrary to the prevailing ideology, the paper suggests that under certain conditions the mass expansion of higher education can contribute to greater income inequality. These conditions are related to three important variables not usually considered in the education-income distribution model: rising returns to university education relative to secondary and primary education, decreasing public spending differences between higher and lower levels of education, and increasing spending differences between elite and mass universities. All three appear to be increasingly common features of educational expansion in developing countries, including large ones such as China, Russia, Brazil, and India, although researchers are just beginning to observe such changing patterns of spending within higher education systems. The paper discusses the role that such payoffs and government education spending patterns can play in contributing to changes in income distribution using suggestive data from the developing countries.
Factors Predicting Dropout From the Reasoning and Rehabilitation Program With Mentally Disordered Offenders
Authors: Cullen Alexis E. , Soria Catherine , Clarke Amory Y. , Dean Kimberlie , Fahy Tom
Published: February 2011

Studies evaluating the implementation of cognitive skills programs with mentally disordered offenders (MDOs) have reported high dropout rates, but little is known about the factors associated with treatment noncompletion. The authors analyzed data from the first randomized controlled trial of the Reasoning and Rehabilitation (R&R) program with MDOs to determine predictors of treatment dropout. Patients with psychotic disorders were recruited from medium-secure hospitals in the United Kingdom. Fifty percent of the 44 participants allocated to receive R&R prematurely terminated treatment. Program dropout was significantly predicted by scores on the Clinical and Risk Management scales of the Historical, Clinical, Risk Management—20, Factor 2 scores of the Psychopathy Checklist—Screening Version, antisocial personality disorder (ASPD), psychopathy, and recent violence. Psychopathy, ASPD, and recent violence emerged as the strongest predictors of dropout in multivariate analyses. Strategies to improve treatment retention should be targeted at MDOs who display high levels of impulsivity, poor behavioral controls, and antisocial or psychopathic traits.
Safety Techniques for Percutaneous Endoscopic Gastrostomy Tube Placement in Pierre Robin Sequence
Authors: Al‐Zubeidi Dina , Rahhal Riad M.
Published: February 2011

Pierre Robin Sequence (PRS) is a craniofacial anomaly characterized by a triad of micrognathia, glossoptosis, and cleft palate. Infants with PRS frequently have feeding problems that may require supplemental nutrition through a nasogastric or gastrostomy tube. Very few published studies have illustrated the most appropriate method for securing an enteral feeding route in this patient population. One case report described a major complication leading to death from airway compromise following percutaneous endoscopic gastrostomy (PEG) tube placement. The authors describe a case of an infant with PRS who underwent successful PEG tube placement without complications, and they highlight certain techniques to improve procedure success and patient safety.
Evaluation of shunting flow differences in varied conditions in a simulated adult CPB model during normothermia
Authors: Xin Duan  , Bingyang Ji  , Gang Liu  , Qingfeng Li  , Jinping Liu  , Kun Yu  , Yue Tang  , Cun Long
Published: February 2011

Background: It is well documented that lower pump flow during clinical cardiopulmonary bypass (CPB) procedures may be significantly detrimental to tissues and organs. The major cause of hypoperfusion is due to shunting flow existing in the closed CPB circuits. The purpose of this investigation was to evaluate various shunting flow conditions in a simulated adult CPB model under normothermia.

Materials and Methods: The pseudo adult patient undergoing CPB was established with an extracorporeal circuit. The pre-oxygenator flow, post-filter flow and purge line pressure were recorded. The temperature of the circuit was kept around 36°C using a heat-cooler. The pseudo patient was subjected to five pump flow rates ranging from 3000 to 5000 ml/min (500 ml/min increments), and post-filter pressure was varied from 120—220 mmHg (20 mmHg increments) using a single, static roller pump. Four different shunting states were measured with two flowmeters.

Results: When the pump flow was constant, the percentage of shunting flow increased as the post-filter pressure increased in State 1. However, when the post-filter pressure was constant, the trend of the shunting flow was the opposite. Purge line pressure increased with the increase of the post-filter pressure at a constant pump flow rate in State 1. The shunting flow for State 2 was the largest of the four states. The shunting flow for State 3 was similar to State 4. Conclusion: During different states of shunt opening, varying degrees of blood flow were diverted away from the arterial line. Shunting of blood flow may, therefore, result in hypoperfusion in the patient.
Tackling barriers to entrepreneurship in a deprived urban neighbourhood
Authors: Williams Nick , Williams Colin C
Published: February 2011

Harnessing entrepreneurship in deprived urban neighbourhoods (DUNs) is a key aspect of enterprise development policy. The aim of this article is to explore the barriers to entrepreneurship in DUNs, and how policy can help tackle these barriers. To do this, it reports the results of a face-to-face survey with 459 respondents and a further 18 in-depth follow-up interviews with those identifying themselves as entrepreneurs or potential entrepreneurs in the Leeds Local Enterprise Growth Initiative (LEGI) area. This provides evidence that individuals living in these DUNs face both direct barriers to engaging in entrepreneurial endeavour, such as lack of self-belief and confidence, and lack of affordable workspace, as well as indirect barriers such as perceptions of place, fear of crime and financial lending hurdles. The article concludes by arguing for a holistic policy approach towards harnessing entrepreneurship in DUNs that tackles not only the direct but also the indirect barriers to entrepreneurship.
Managing decline in inner city retail centres: From case study to conceptualization
Authors: Whysall Paul
Published: February 2011

This article focuses around a study of declining shopping provision in Hyson Green, a deprived area of inner Nottingham, since 1973. It starts by reviewing issues surrounding inner city retail decline that prompt policy concerns, including aspects of health and diet, local economy, environmental impacts, urban structure and social considerations. Hyson Green has undergone major upheavals since the 1960s including construction and subsequent demolition of extensive local authority housing, the development of a superstore, and construction of a tram route. Mainstream retail outlets declined from 138 in 1977 to just 48 units. However, recent policies enabling conversions to community and residential uses have stemmed the growth of vacant units, particularly at the extremities. Berry's conceptualization of commercial blight, derived in Chicago in the 1960s, provides a framework for understanding policies addressing shopping decline both in the case study and potentially more generally in similar areas of shopping contraction.
The effects of dynamic ankle-foot orthoses in chronic stroke patients at three-month follow-up: a randomized controlled trial
Authors: Erel Suat , Uygur Fatma , Engin Şimşek İbrahim , Yakut Yakut
Published: February 2011

Objective: To investigate the short- and long-term effects of dynamic ankle foot orthoses on functional ambulation activities in chronic hemiparetic patients.

Design: Randomized controlled trial.

Setting: University’s neurological rehabilitation outpatient clinic and orthotics department.

Subjects: Twenty-eight chronic hemiparetic patients of level 3–5 according to Functional Ambulation Classification and with a maximum spasticity level of 3 according to Modified Ashworth Scale, were randomly assigned to the study and control groups.

Interventions: The control group (n = 14) was assessed with tennis shoes whereas the study group (n = 14) was assessed initially with tennis shoes and after three months with dynamic ankle foot orthosis.

Measures: Functional Reach, Timed Up and Go, Timed Up Stairs, Timed Down Stairs, gait velocity and Physiological Cost Index.

Results: In the initial assessment no difference was found between the groups for any of the measured parameters (P > 0.05). After three months, intergroup comparisons while the patients in the study group were wearing dynamic ankle-foot orthosis showed a significant difference in favour of the study group for Timed Up Stairs 12.00 (10.21) seconds study versus 15.00 (7.29) seconds control group; for gait velocity 0.99 (0.45) m/s study versus 0.72 (0.20) m/s control group and for Physiological Cost Index 0.12 (0.06) beats/min study versus 0.28 (0.13) beats/min control group (P < 0.05). No difference was found between the groups for Functional Reach, Timed Up and Go, Timed Down Stairs (P > 0.05).

Conclusion: Chronic hemiparetic patients may benefit from using dynamic ankle-foot orthosis.
Do nursing homes for older people have the support they need to provide end-of-life care? A mixed methods enquiry in England
Authors: Seymour Jane E , Kumar Arun , Froggatt Katherine
Published: February 2011

Nursing homes are a common site of death, but older residents receive variable quality of end-of-life care. We used a mixed methods design to identify external influences on the quality of end-of-life care in nursing homes. Two qualitative case studies were conducted and a postal survey of 180 nursing homes surrounding the case study sites. In the case studies, qualitative interviews were held with seven members of nursing home staff and 10 external staff. Problems in accessing support for end-of-life care reported in the survey included variable support by general practitioners (GPs), reluctance among GPs to prescribe appropriate medication, lack of support from other agencies, lack of out of hours support, cost of syringe drivers and lack of access to training. Most care homes were implementing a care pathway. Those that were not rated their end-of-life care as in need of improvement or as average. The case studies suggest that critical factors in improving end-of-life care in nursing homes include developing clinical leadership, developing relationships with GPs, the support of ‘key’ external advocates and leverage of additional resources by adoption of care pathway tools.