bluuebunny/crossref_metadata_2025 huggingface dataset:
ALP
Authors: Calagari Kiana , Pakravan Mohammad Reza , Shirmohammadi Shervin , Hefeeda Mohamed
Published: January 2015

There has been an increasing demand for interactive video transmission over the Internet for applications such as video conferencing, video calls, and telepresence applications. These applications are increasingly moving towards providing High Definition (HD) video quality to users. A key challenge in these applications is to preserve the quality of video when it is transported over best-effort networks that do not guarantee lossless transport of video packets. In such conditions, it is important to protect the transmitted video by using intelligent and adaptive protection schemes. Applications such as HD video conferencing require live interaction among participants, which limits the overall delay the system can tolerate. Therefore, the protection scheme should add little or no extra delay to video transport. We propose a novel Adaptive Loss Protection (ALP) scheme for interactive HD video applications such as video conferencing and video chats. This scheme adds negligible delay to the transmission process and is shown to achieve better quality than other schemes in lossy networks. The proposed ALP scheme adaptively applies four different protection modes to cope with the dynamic network conditions, which results in high video quality in all network conditions. Our ALP
scheme
consists of four protection
modes
; each of these modes utilizes a protection
method
. Two of the modes rely on the state-of-the-art protection methods, and we propose a new Integrated Loss Protection (ILP) method for the other two modes. In the ILP method we integrate three factors for distributing the protection among packets. These three factors are error propagation, region of interest and header information. In order to decide when to switch between the protection modes, a new metric is proposed based on the effectiveness of each mode in performing protection, rather than just considering network statistics such as packet loss rate. Results show that by using this metric not only the overall quality will be improved but also the variance of quality will decrease. One of the main advantages of the proposed ALP scheme is that it does not increase the bit rate overhead in poor network conditions. Our results show a significant gain in video quality, up to 3dB PSNR improvement is achieved using our scheme, compared to protecting all packets equally with the same amount of overhead.
Aesthetics-Guided Summarization from Multiple User Generated Videos
Authors: Zhang Ying , Zhang Luming , Zimmermann Roger
Published: January 2015

In recent years, with the rapid development of camera technology and portable devices, we have witnessed a flourish of user generated videos, which are gradually reshaping the traditional professional video oriented media market. The volume of user generated videos in repositories is increasing at a rapid rate. In today's video retrieval systems, a simple query will return many videos which seriously increase the viewing burden. To manage these video retrievals and provide viewers with an efficient way to browse, we introduce a system to automatically generate a summarization from multiple user generated videos and present their salience to viewers in an enjoyable manner. Among multiple consumer videos, we find their qualities to be highly diverse due to various factors such as a photographer's experience or environmental conditions at the time of capture. Such quality inspires us to include a video quality evaluation component into the video summarization since videos with poor qualities can seriously degrade the viewing experience. We first propose a probabilistic model to evaluate the aesthetic quality of each user generated video. This model compares the rich aesthetics information from several well-known photo databases with generic unlabeled consumer videos, under a human perception component indicating the correlation between a video and its constituting frames. Subjective studies were carried out with the results indicating that our method is reliable. Then a novel graph-based formulation is proposed for the multi-video summarization task. Desirable summarization criteria is incorporated as the graph attributes and the problem is solved through a dynamic programming framework. Comparisons with several state-of-the-art methods demonstrate that our algorithm performs better than other methods in generating a skimming video in preserving the essential scenes from the original multiple input videos, with smooth transitions among consecutive segments and appealing aesthetics overall.
Mitigating Prefetcher-Caused Pollution Using Informed Caching Policies for Prefetched Blocks
Authors: Seshadri Vivek , Yedkar Samihan , Xin Hongyi , Mutlu Onur , Gibbons Phillip B. , Kozuch Michael A. , Mowry Todd C.
Published: January 2015

Many modern high-performance processors prefetch blocks into the on-chip cache. Prefetched blocks can potentially pollute the cache by evicting more useful blocks. In this work, we observe that both accurate and inaccurate prefetches lead to cache pollution, and propose a comprehensive mechanism to mitigate prefetcher-caused cache pollution.

First, we observe that over 95% of useful prefetches in a wide variety of applications are not reused after the first demand hit (in secondary caches). Based on this observation, our first mechanism simply demotes a prefetched block to the lowest priority on a demand hit. Second, to address pollution caused by inaccurate prefetches, we propose a self-tuning prefetch accuracy predictor to predict if a prefetch is accurate or inaccurate. Only predicted-accurate prefetches are inserted into the cache with a high priority.

Evaluations show that our final mechanism, which combines these two ideas, significantly improves performance compared to both the baseline LRU policy and two state-of-the-art approaches to mitigating prefetcher-caused cache pollution (up to 49%, and 6% on average for 157 two-core multiprogrammed workloads). The performance improvement is consistent across a wide variety of system configurations.
Using Template Matching to Infer Parallel Design Patterns
Authors: Huda Zia Ul , Jannesari Ali , Wolf Felix
Published: January 2015

The triumphant spread of multicore processors over the past decade increases the pressure on software developers to exploit the growing amount of parallelism available in the hardware. However, writing parallel programs is generally challenging. For sequential programs, the formulation of design patterns marked a turning point in software development, boosting programmer productivity and leading to more reusable and maintainable code. While the literature is now also reporting a rising number of parallel design patterns, programmers confronted with the task of parallelizing an existing sequential program still struggle with the question of which parallel pattern to apply where in their code. In this article, we show how template matching, a technique traditionally used in the discovery of sequential design patterns, can also be used to support parallelization decisions. After looking for matches in a previously extracted dynamic dependence graph, we classify code blocks of the input program according to the structure of the parallel patterns we find. Based on this information, the programmer can easily implement the detected pattern and create a parallel version of his or her program. We tested our approach with six programs, in which we successfully detected pipeline and do-all patterns.
mHealth + Proactive Well-being = Wellth Creation
Authors: Churchill Elizabeth F. , schraefel m.c.
Published: January 2015

This forum is dedicated to personal health in all its many facets: decision-making, goal setting, celebration, discovery, reflection, and coordination, among others. We look at innovations in interactive technologies and how they help address current critical healthcare challenges.
--- Gillian R. Hayes, Editor
Public policy and violence in video games
Authors: Chakraborty Joyram , Chakraborty Nirali M.
Published: January 2015

Public policy plays an influential role in the work we do as HCI researchers, interaction designers, and practitioners.
Public policy
, a broad term, includes both government policy and policy within non-governmental organizations. This forum focuses on topics at the intersection of human-computer interaction and public policy.
--- Jonathan Lazar, Editor
Perfect Reconstructability of Control Flow from Demand Dependence Graphs
Authors: Bahmann Helge , Reissmann Nico , Jahre Magnus , Meyer Jan Christian
Published: January 2015

Demand-based dependence graphs (DDGs), such as the (Regionalized) Value State Dependence Graph ((R)VSDG), are intermediate representations (IRs) well suited for a wide range of program transformations. They explicitly model the flow of data and state, and only implicitly represent a restricted form of control flow. These features make DDGs especially suitable for automatic parallelization and vectorization, but cannot be leveraged by practical compilers without efficient construction and destruction algorithms. Construction algorithms remodel the arbitrarily complex control flow of a procedure to make it amenable to DDG representation, whereas destruction algorithms reestablish control flow for generating efficient object code. Existing literature presents solutions to both problems, but these impose structural constraints on the generatable control flow, and omit qualitative evaluation.

The key contribution of this article is to show that there is no intrinsic structural limitation in the control flow directly extractable from RVSDGs. This fundamental result originates from an interpretation of loop repetition and decision predicates as computed continuations, leading to the introduction of the
predicate continuation
normal form. We provide an algorithm for constructing RVSDGs in predicate continuation form, and propose a novel destruction algorithm for RVSDGs in this form. Our destruction algorithm can generate arbitrarily complex control flow; we show this by proving that the original CFG an RVSDG was derived from can, apart from overspecific detail, be reconstructed perfectly. Additionally, we prove termination and correctness of these algorithms. Furthermore, we empirically evaluate the performance, the representational overhead at compile time, and the reduction in branch instructions compared to existing solutions. In contrast to previous work, our algorithms impose no additional overhead on the control flow of the produced object code. To our knowledge, this is the first scheme that allows the original control flow of a procedure to be recovered from a DDG representation.
Quo vadis Open-IX?
Authors: Chatzis Nikolaos , Smaragdakis Georgios , Feldmann Anja , Willinger Walter
Published: January 2015

The recently launched initiative by the Open-IX Association (OIX) to establish the European-style Internet eXchange Point (IXP)model in the US suggests an intriguing strategy to tackle a problem that some Internet stakeholders in the US consider to be detrimental to their business; i.e., a lack of diversity in available peering opportunities. We examine in this paper the cast of Internet stakeholders that are bound to play a critical role in determining the fate of this Open-IX effort. These include the large content and cloud providers, CDNs, Tier-1 ISPs, the well-established and some of the newer commercial datacenter and colocation companies, and the largest IXPs in Europe. In particular, we comment on these different parties' current attitudes with respect to public and private peering and discuss some of the economic arguments that will ultimately determine whether or not the currently pursued strategy by OIX will succeed in achieving the main OIX-articulated goal -- a more level playing field for private and public peering in the US such that the actual demand and supply for the different peering opportunities will be reflected in the cost structure.
The Plastid Terminal Oxidase: Its Elusive Function Points to Multiple Contributions to Plastid Physiology
Authors: Nawrocki Wojciech J. , Tourasse Nicolas J. , Taly Antoine , Rappaport Fabrice , Wollman Francis-André
Published: January 2015

Plastids have retained from their cyanobacterial ancestor a fragment of the respiratory electron chain comprising an NADPH dehydrogenase and a diiron oxidase, which sustain the so-called chlororespiration pathway. Despite its very low turnover rates compared with photosynthetic electron flow, knocking out the plastid terminal oxidase (PTOX) in plants or microalgae leads to severe phenotypes that encompass developmental and growth defects together with increased photosensitivity. On the basis of a phylogenetic and structural analysis of the enzyme, we discuss its physiological contribution to chloroplast metabolism, with an emphasis on its critical function in setting the redox poise of the chloroplast stroma in darkness. The emerging picture of PTOX is that of an enzyme at the crossroads of a variety of metabolic processes, such as, among others, the regulation of cyclic electron transfer and carotenoid biosynthesis, which have in common their dependence on the redox state of the plastoquinone pool, set largely by the activity of PTOX in darkness.
The Development and Course of Bipolar Spectrum Disorders: An Integrated Reward and Circadian Rhythm Dysregulation Model
Authors: Alloy Lauren B. , Nusslock Robin , Boland Elaine M.
Published: January 2015

In this article, we present and review the evidence for two major biopsychosocial theories of the onset and course of bipolar spectrum disorders (BSDs) that integrate behavioral, environmental, and neurobiological mechanisms: the reward hypersensitivity and the social/circadian rhythm disruption models. We describe the clinical features, spectrum, age of onset, and course of BSDs. We then discuss research designs relevant to demonstrating whether a hypothesized mechanism represents a correlate, vulnerability, or predictor of the course of BSDs, as well as important methodological issues. We next present the reward hypersensitivity model of BSD, followed by the social/circadian rhythm disruption model of BSD. For each model, we review evidence regarding whether the proposed underlying mechanism is associated with BSDs, provides vulnerability to the onset of BSDs, and predicts the course of BSDs. We then present a new integrated reward/circadian rhythm (RCR) dysregulation model of BSD and discuss how the RCR model explains the symptoms, onset, and course of BSDs. We end with recommendations for future research directions.
Ultracold Atoms Out of Equilibrium
Authors: Langen Tim , Geiger Remi , Schmiedmayer Jörg
Published: January 2015

The relaxation of isolated quantum many-body systems is a major unsolved problem connecting statistical and quantum physics. Studying such relaxation processes remains a challenge despite considerable efforts. Experimentally, it requires the creation and manipulation of well-controlled and truly isolated quantum systems. In this context, ultracold neutral atoms provide unique opportunities to understand nonequilibrium phenomena because of the large set of available methods to isolate, manipulate, and probe these systems. Here, we give an overview of the rapid experimental progress that has been made in the field over the past few years and highlight some of the questions that may be explored in the future.
Jadeitites and Plate Tectonics
Authors: Harlow George E. , Tsujimori Tatsuki , Sorensen Sorena S.
Published: January 2015

Jadeitite is a relatively rare, very tough rock composed predominantly of jadeite and typically found associated with tectonic blocks of high-pressure/low-temperature metabasaltic rocks (e.g., eclogite, blueschist) in exhumed serpentinite-matrix mélanges. Studies over the past ∼20 years have interpreted jadeitite either as the direct hydrous fluid precipitate from subduction channel dewatering into the overlying mantle wedge or as the metasomatic replacement by such fluids of oceanic plagiogranite, graywacke, or metabasite along the channel margin. Thus, jadeitites directly sample and record fluid transport in the subduction factory and provide a window into this geochemical process that is critical to a major process in the Earth system. They record the remarkable transport of large ion lithophile elements, such as Li, Ba, Sr, and Pb, as well as elements generally considered more refractory, such as U, Th, Zr, and Hf. Jadeitite is also the precious form of jade, utilized since antiquity in the form of tools, adornments, and symbols of prestige.
Methodological and Substantive Issues in Conducting Multinational and Cross-Cultural Research
Authors: Spector Paul E. , Liu Cong , Sanchez Juan I.
Published: January 2015

The rising importance of multinational and cross-cultural research has spurred the development of methodologies to adequately study human phenomena in organizations across culture and place. Disentangling culture and location from potential confounding variables is an underlying issue in conducting comparative studies. Research designs allow comparisons of countries and culture groups, as well as isolate the potential impact of cultural variables. Sampling methods must be chosen to control for differences that confound the cultural variables of interest with other characteristics of samples. Translation and back-translation are necessary when studies cross linguistic boundaries. Measures that compare cultural and national groups should be checked for measurement equivalence/invariance using one or more tools based on confirmatory factor analysis or item response theory. Some sources of invariance can be found in culturally determined response biases. In the same investigation, it is advisable to pair qualitative methods, which help characterize culture-specific factors, with quantitative methods, which help disentangle their confounds.
Translating Evidence into Population Health Improvement: Strategies and Barriers
Authors: Woolf Steven H. , Purnell Jason Q. , Simon Sarah M. , Zimmerman Emily B. , Camberos Gabriela J. , Haley Amber , Fields Robert P.
Published: January 2015

Among the challenges facing research translation—the effort to move evidence into policy and practice—is that key questions chosen by investigators and funders may not always align with the information priorities of decision makers, nor are the findings always presented in a form that is useful for or relevant to the decisions at hand. This disconnect is a problem particularly for population health, where the change agents who can make the biggest difference in improving health behaviors and social and environmental conditions are generally nonscientists outside of the health professions. To persuade an audience that does not read scientific journals, strong science may not be enough to elicit change. Achieving influence in population health often requires four ingredients for success: research that is responsive to user needs, an understanding of the decision-making environment, effective stakeholder engagement, and strategic communication. This article reviews the principles and provides examples from a national and local initiative.
Efficacy of prophylactic flavan-3-ol in permanent focal ischemia in 12-mo-old mice
Authors: Leonardo Christopher C. , Mendes Monique , Ahmad Abdullah S. , Doré Sylvain
Published: January 2015

The consumption of flavan-3-ol-containing foods, including (−)-epicatechin (EC), has been linked to lower incidence of cardiovascular disease and stroke. We previously demonstrated nuclear transcription factor erythroid 2p45-related factor-2 (Nrf2) -dependent EC efficacy in reducing stroke-induced deficits in 2-mo-old mice; yet stroke is primarily a disease of the elderly. Because neuroinflammation, oxidative stress, and vascular dysfunction are hallmarks of aging, we tested whether Nrf2 mediates EC efficacy in aging mice through modulation of glial responses and blood brain barrier permeability. First, we compared anastomosis in naïve wild-type and C57BL/6 Nrf2−/−mice to identify potential differences in cerebrovascular architecture. Data showed no significant differences in the number of anastomoses or mean intersection points, indicating similar gross vascular physiology. To assess efficacy and mechanisms of protection, wild-type or Nrf2−/−mice were administered the minimum effective EC dose established in our previous studies before the permanent distal middle cerebral artery occlusion. Similar to previous results with young mice, 12-mo-old wild types also showed significant reductions in infarct volume (41.01 ± 29.57%) and improved performance in removing adhesive tape relative to vehicle-treated controls, whereas a trend toward protection was observed in Nrf2−/−. However, EC did not reduce immunoreactivity for the microglia/macrophage marker anti-ionized calcium-binding adapter molecule 1, suggesting that dampened activation/recruitment did not account for EC protection. Furthermore, there were no differences in mouse IgG extravasation or spontaneous hemorrhage between EC-treated groups. These data demonstrate that EC protection occurs independent of microglia/macrophage modulation or blood brain barrier preservation, suggesting that the glial cell responses in young mice are compensatory to another, and potentially novel, protective mechanism.
Ca2+entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance
Authors: Hoffman Nicholas E. , Miller Barbara A. , Wang JuFang , Elrod John W. , Rajan Sudasan , Gao Erhe , Song Jianliang , Zhang Xue-Qian , Hirschler-Laszkiewicz Iwona , Shanmughapriya Santhanam , Koch Walter J. , Feldman Arthur M. , Madesh Muniswamy , Cheung Joseph Y.
Published: January 2015

Ubiquitously expressed Trpm2 channel limits oxidative stress and preserves mitochondrial function. We first demonstrated that intracellular Ca2+concentration increase after Trpm2 activation was due to direct Ca2+influx and not indirectly via reverse Na+/Ca2+exchange. To elucidate whether Ca2+entry via Trpm2 is required to maintain cellular bioenergetics, we injected adenovirus expressing green fluorescent protein (GFP), wild-type (WT) Trpm2, and loss-of-function (E960D) Trpm2 mutant into left ventricles of global Trpm2 knockout (gKO) or WT hearts. Five days post-injection, gKO-GFP heart slices had higher reactive oxygen species (ROS) levels but lower oxygen consumption rate (OCR) than WT-GFP heart slices. Trpm2 but not E960D decreased ROS and restored OCR in gKO hearts back to normal levels. In gKO myocytes expressing Trpm2 or its mutants, Trpm2 but not E960D reduced the elevated mitochondrial superoxide (O2.−) levels in gKO myocytes. After hypoxia-reoxygenation (H/R), Trpm2 but not E906D or P1018L (inactivates Trpm2 current) lowered O2.−levels in gKO myocytes and only in the presence of extracellular Ca2+, indicating sustained Ca2+entry is necessary for Trpm2-mediated preservation of mitochondrial function. After ischemic-reperfusion (I/R), cardiac-specific Trpm2 KO hearts exhibited lower maximal first time derivative of LV pressure rise (+dP/d t) than WT hearts in vivo. After doxorubicin treatment, Trpm2 KO mice had worse survival and lower +dP/d t. We conclude 1) cardiac Trpm2-mediated Ca2+influx is necessary to maintain mitochondrial function and protect against H/R injury; 2) Ca2+influx via cardiac Trpm2 confers protection against H/R and I/R injury by reducing mitochondrial oxidants; and 3) Trpm2 confers protection in doxorubicin cardiomyopathy.
Matrix metalloproteinase (MMP)-19-deficient fibroblasts display a profibrotic phenotype
Authors: Jara Paul , Calyeca Jazmin , Romero Yair , Plácido Luis , Yu Guoying , Kaminski Naftali , Maldonado Vilma , Cisneros José , Selman Moisés , Pardo Annie
Published: January 2015

Idiopathic pulmonary fibrosis (IPF) is a progressive and usually lethal interstitial lung disease of unknown etiology characterized by aberrant activation of epithelial cells that induce the migration, proliferation and activation of fibroblasts. The resulting distinctive fibroblastic/myofibroblastic foci are responsible for the excessive extracellular matrix (ECM) production and abnormal lung remodeling. We have recently found that matrix metalloproteinase 19 (MMP-19)-deficient ( Mmp19−/−) mice develop an exaggerated bleomycin-induced lung fibrosis, but the mechanisms are unclear. In this study, we explored the effect of MMP-19 deficiency on fibroblast gene expression and cell behavior. Microarray analysis of Mmp19−/− lung fibroblasts revealed the dysregulation of several profibrotic pathways, including ECM formation, migration, proliferation, and autophagy. Functional studies confirmed these findings. Compared with wild-type mice, Mmp19−/− lung fibroblasts showed increased α1 (I) collagen gene and collagen protein production at baseline and after transforming growth factor-β treatment and increased smooth muscle-α actin expression ( P < 0.05). Likewise, Mmp19-deficient lung fibroblasts showed a significant increase in proliferation ( P < 0.01) and in transmigration and locomotion over Boyden chambers coated with type I collagen or with Matrigel ( P < 0.05). These findings suggest that, in lung fibroblasts, MMP-19 has strong regulatory effects on the synthesis of key ECM components, on fibroblast to myofibroblast differentiation, and in migration and proliferation.
Oxidized phospholipids protect against lung injury and endothelial barrier dysfunction caused by heat-inactivated Staphylococcus aureus
Authors: Meliton Angelo Y. , Meng Fanyong , Tian Yufeng , Sarich Nicolene , Mutlu Gokhan M. , Birukova Anna A. , Birukov Konstantin G.
Published: January 2015

Increased endothelial cell (EC) permeability and vascular inflammation along with alveolar epithelial damage are key features of acute lung injury (ALI). Products of 1-palmitoyl-2-arachidonoyl- sn-glycero-3-phosphorylcholine oxidation (OxPAPC) showed protective effects against inflammatory signaling and vascular EC barrier dysfunction induced by gram-negative bacterial wall lipopolysaccharide (LPS). We explored the more general protective effects of OxPAPC and investigated whether delayed posttreatment with OxPAPC boosts the recovery of lung inflammatory injury and EC barrier dysfunction triggered by intratracheal injection of heat-killed gram-positive Staphylococcus aureus (HKSA) bacteria. HKSA-induced pulmonary EC permeability, activation of p38 MAP kinase and NF-κB inflammatory cascades, secretion of IL-8 and soluble ICAM1, fibronectin deposition, and expression of adhesion molecules ICAM1 and VCAM1 by activated EC were significantly attenuated by cotreatment as well as posttreatment with OxPAPC up to 16 h after HKSA addition. Remarkably, posttreatment with OxPAPC up to 24 h post-HKSA challenge dramatically accelerated lung recovery by restoring lung barrier properties monitored by Evans blue extravasation and protein content in bronchoalveolar lavage (BAL) fluid and reducing inflammation reflected by decreased MIP-1, KC, TNF-α, IL-13 levels and neutrophil count in BAL samples. These studies demonstrate potent in vivo and in vitro protective effects of posttreatment with anti-inflammatory oxidized phospholipids in the model of ALI caused by HKSA. These results warrant further investigations into the potential use of OxPAPC compounds combined with antibiotic therapies as a treatment of sepsis and ALI induced by gram-positive bacterial pathogens.
Inhibition of protein phosphatase 1 reverses alcohol-induced ciliary dysfunction
Authors: Price Michael E. , Pavlik Jacqueline A. , Sisson Joseph H. , Wyatt Todd A.
Published: January 2015

Airway mucociliary clearance is a first-line defense of the lung against inhaled particles and debris. Among individuals with alcohol use disorders, there is an increase in lung diseases. We previously identified that prolonged alcohol exposure impairs mucociliary clearance, known as alcohol-induced ciliary dysfunction (AICD). Cilia-localized enzymes, known as the ciliary metabolon, are key to the pathogenesis of AICD. In AICD, cyclic nucleotide-dependent ciliary kinases, which modulate phosphorylation to regulate cilia beat, are desensitized. We hypothesized that alcohol activates cilia-associated protein phosphatase 1 (PP1) activity, driving phosphorylation changes of cilia motility regulatory proteins. To test this hypothesis we identified the effects of prolonged alcohol exposure on phosphatase activity, cilia beat, and kinase responsiveness and cilia-associated phosphorylation targets when stimulated by β-agonist or cAMP. Prolonged alcohol activated PP1 and blocked cAMP-dependent cilia beat and protein kinase A (PKA) responsiveness and phosphorylation of a 29-kDa substrate of PKA. Importantly, prolonged alcohol-induced phosphatase activation was inhibited by the PP1 specific inhibitor, inhibitor-2 (I-2), restoring cAMP-stimulated cilia beat and PKA responsiveness and phosphorylation of the 29-kDa substrate. The I-2 inhibitory effect persisted in tissue, cell, and isolated cilia-organelle models, highlighting the association of ciliary metabolon-localized enzymes to AICD. Prolonged alcohol exposure drives ciliary metabolon-localized PP1 activation. PP1 activation modifies phosphorylation of a 29-kDa protein related to PKA activity. These data reinforce our previous findings that alcohol is acting at the level of the ciliary metabolon to cause ciliary dysfunction and identifies PP1 as a therapeutic target to prevent or reverse AICD.
Object‐Oriented Implementation of Software for Solving Ordinary Differential Equations
Authors: Gustafsson Kjell
Published: January 2015

We describe an object‐oriented implementation of numerical integration methods for solving ordinary differential equations. Software components that are common to many different integration methods have been identified and implemented in such a way that they can be reused. This facilitates the design of a uniform user interface and makes the task of implementing a new integration method fairly modest. The sharing of code in this type of implementation also allows for less subjective comparisons of the result from different integration methods.
Applications Demand Class‐Specific Optimizations: The C++ Compiler Can Do More
Authors: Angus Ian G.
Published: January 2015

So far C++ has made few inroads into the realm of scientific computing, which is still largely dominated by Fortran. Of the few attempts that have been made to apply C++ to numerically intensive codes, the results have often suffered from severe performance problems. A careful examination of these problems indicates that they are unlikely to be solved by incremental improvements in compiler optimization technology. The flow of this article will: motivate the discussion by describing a common efficiency problem that arises when numerical codes are programmed in C++; discuss some potential solution strategies that we believe are viable in the near term, but not over the long term; introduce a mechanism by which a compiler can load domain‐specific and class‐specific optimizations on an as needed basis. A simple interface that will enable this feature will be presented. Althoug our immediate motivation is that of numerically intensive codes, our approach is applicable to all application domains.
Parallelization of a Three‐Dimensional Shallow‐Water Estuary Model on the KSR‐1
Authors: Korn C. FalcÓ , Bull J. M. , Riley G. D. , Stansby P. K.
Published: January 2015

Flows in estuarial and coastal regions may be described by the shallow‐water equations. The processes of pollution transport, sediment transport, and plume dispersion are driven by the underlying hydrodynamics. Accurate resolution of these processes requires a three‐dimensional formulation with turbulence modeling, which is very demanding computationally. A numerical scheme has been developed which is both stable and accurate – we show that this scheme is also well suited to parallel processing, making the solution of massive complex problems a practical computing possibility. We describe the implementation of the numerical scheme on a Kendall Square Research KSR‐1 multiprocessor, and present experimental results which demonstrate that a problem requiring 600,000 mesh points and 6,000 time steps can be solved in under 8 hours using 32 processors.
Structured Parallel Programming: How Informatics Can Help Overcome the Software Dilemma
Authors: Burkhart Helmar , Frank Robert , Hächler Guido
Published: January 2015

The state‐of‐the‐art programming of parallel computers is far from being successful. The main challenge today is, therefore, the development of techniques and tools that improve programmers′ productivity. Programmability, portability, and reusability are key issues to be solved. In this article we shall report about our ongoing efforts in this direction. After a short discussion of the software dilemma found today, we shall present the Basel approach. We shall summarize our algorithm description methodology and discuss the basic concepts of the proposed skeleton language. An algorithmic example and comments on implementation aspects will explain our work in more detail. We shall summarize the current state of the implementation and conclude with a discussion of related work.
Limits of Flow‐Cytometry Histogram Analysis Methods to Assess Bladder Tumour Antigen Expression
Authors: Chabanas Agnès , Rambeaud Jean‐Jacques , Huo Hong-Hsu , Seigneurin Daniel , Lawrence Jean-Jacques
Published: January 2015

Tumour‐associated antigens detected in cells obtained from bladder washings or tumours are useful markers in bladder cancer. Flow cytometry is commonly used to quantify immuno‐stained cells. A straightforward way to analyze data is to count the fluorescent cells above a threshold empirically determined on a control histogram representation. However, specific antigens expressed at highly variable rates give rise to wide range distributions in flow cytometry as illustrated when a mucin antigen for urinary bladder was titrated by M344 monoclonal antibody in urothelial cancer cells. We have evaluated several methods of background estimation and subtraction in order to determine the proportion of M344 Mab positive cells. These include threshold setting (Histogram Shape Dependent (HSD) threshold developped in this study, 2% preset or 5% preset background), subtraction of the blank from the test histograms, and Kolmogorov–Smirnov statistical test. The HSD method appeared to be a more reliable method for background estimation; however, in the case of very low antigen expression, where specific fluorescence histograms could hardly be distinguished from that of the background, fluorescence microscopy remained the only valid method, since it allowed the distinction between specific and non‐specific fluorescence on the basis of structural differences between the two.
Precise Analysis of Array Usage in Scientific Programs
Authors: Manjunathaiah M. , Nicole Denis A.
Published: January 2015

The automatic transformation of sequential programs for efficient execution on parallel computers involves a number of analyses and restructurings of the input. Some of these analyses are based on computing array sections, a compact description of a range of array elements. Array sections describe the set of array elements that are either read or written by program statements. These sections can be compactly represented using shape descriptors such as regular sections, simple sections, or generalized convex regions. However, binary operations such as Union performed on these representations do not satisfy a straightforward closure property, e.g., if the operands to Union are convex, the result may be nonconvex. Approximations are resorted to in order to satisfy this closure property. These approximations introduce imprecision in the analyses and, furthermore, the imprecisions resulting from successive operations have a cumulative effect. Delayed merging is a technique suggested and used in some of the existing analyses to minimize the effects of approximation. However, this technique does not guarantee an exact solution in a general setting. This article presents a generalized technique to precisely compute Union which can overcome these imprecisions.
Relevance of Chromatin Features in the Progression of Esophageal Epithelial Severe Dysplasia
Authors: Gao Feng , Jütting Uta , Rodenacker Karsten , Gais Peter , Lin Pei‐zhong
Published: January 2015

Since 1983, a long‐term clinical trial of esophageal carcinoma chemoprevention has been conducted in a high‐risk area in China. From this study, 25 esophageal severe dysplasia patients without therapy were selected for analysis. After 5‐year follow‐ups, 14 cases progressed to esophageal carcinoma, while the other 11 cases remained stable. Three Papanicolaou’s smears were used for each case, including one from the esophageal cytological examination at the beginning, two from the re‐examinations three and five years later respectively. About 100 visually normal intermediate cells were randomly collected per slide by high resolution image analysis. More than 100 features (morphologic, densitometric, textural) were extracted. The classifications were made by means of stepwise linear discriminate analysis at the single cell level as on the specimen level using up to ten features. In all three comparisons of patients with progression and with regression at time of diagnosis, three years after diagnosis and five years later, the correct cell classification rates were about 70%. The subsequent specimen classifications by means of the a posteriori probability (APOP) distribution of the cells in each case led to 80% correct classification. All selected features reflected the chromatin structure of nuclei. The result demonstrated that the chromatin structures of esophageal epithelial cells in severely dysplasic patients are different between cases with and without progression. These results suggest the possibility of the application of image analysis in the clinical trials to find the dysplasia patients with higher risk of progression, in order to reduce the number of patients for therapy.
Opus: A Coordination Language for Multidisciplinary Applications
Authors: Chapman Barbara , Haines Matthew , Mehrotra Piyush , Zima Hans , Van Rosendale John
Published: January 2015

Data parallel languages, such as High Performance Fortran, can be successfully applied to a wide range of numerical applications.However, many advanced scientific and engineering applications are multidisciplinary and heterogeneous in nature, and thus do not fit well into the data parallel paradigm. In this paper we present Opus, a language designed to fill this gap. The central concept of Opus is a mechanism called ShareD Abstractions (SDA). An SDA can be used as a computation server, i.e., a locus of computational activity, or as a data repository for sharing data between asynchronous tasks. SDAs can be internally data parallel, providing support for the integration of data and task parallelism as well as nested task parallelism. They can thus be used to express multidisciplinary applications in a natural and efficient way. In this paper we describe the features of the language through a series of examples and give an overview of the runtime support required to implement these concepts in parallel and distributed environments.
Heterogeneity of DNA Distribution Pattern in Renal Tumours
Authors: Nenning Hans , Raßler Jörg , Minh Do Hoan
Published: January 2015

The presence of intratumoural heterogeneity in DNA distribution patterns has been accepted. However, most previous studies have not taken this fact into consideration. The value of DNA cytometry depends on its reproducibility. This could be influenced by heterogeneity failure. The aim of the present study is to evaluate intratumoural heterogeneity in renal cell cancer.

A sample of 22 tumours of the kidney was investigated by means of static DNA cytometry: 21 tumours were carcinomas, one was an angiomyolipoma. Probes from seven different locations of each tumour were Feulgen‐stained and measured. The variability of DNA features was determined and correlated with histological grade and type and with tumour size.

There was considerable intratumoural heterogeneity with respect to DNA distribution pattern in 45% of the tumours. Additional non‐diploid tumour‐stemlines and deviation of computed DNA features could be found in several cases by measuring more than one slide per tumour. A correlation between tumour heterogeneity, grading or typing, and tumour size could not be found.

Because these DNA parameters could serve as the foundation of a risk‐adapted treatment, tumour heterogeneity could have clinical consequences. Based on the results of this study we suggest measuring at least three slides per tumour to avoid misinterpretation of DNA measurements in renal cell cancer.
Comparative Quantitative Analysis of Macrophage Populations Defined by CD68 and Carbohydrate Antigens in Normal and Pathologically Altered Human Liver Tissue
Authors: Baldus Stephan E. , Zirbes Thomas K. , Weidner Ion-Corin , Flucke Uta , Dittmar Elke , Thiele Juergen , Dienes Hans P.
Published: January 2015

Liver macrophages, which are involved in the different types of hepatitis, may indirectly induce hepatic fibrogenesis, since they have the possibility to activate hepatic stellate cells and fibroblasts by secretion of TGF‐β , TNF‐α and IL‐1. To evaluate variations of the number of liver macrophages and their subpopulations, a quantification was carried out in normal human liver tissue, fatty liver, fatty liver hepatitis and hepatitis B. Identification was performed by the mab PG‐M1 (anti‐CD68) and, comparatively, four lectins, Griffonia simplicifolia agglutinin I (GSA‐I), Erythrina cristagalli agglutinin (ECA), peanut agglutinin (PNA) and soybean agglutinin (SBA). A slight decrease in the frequency of macrophages in pericentral fields was observable in fatty liver and fatty liver hepatitis as compared to normal liver tissue. On the other hand, the number of CD68+ cells was significantly enhanced in hepatitis B with moderate and severe inflammatory activity. The highest incidence of macrophages was found in portal tracts of liver with fatty liver hepatitis and, particularly, hepatitis B. The fraction of cells stained by ECA, PNA or SBA did not increase significantly under pathological conditions. In contrast, the percentage of GSA‐I binding macrophages was higher in liver parenchyma of hepatitis B and in portal tract macrophages in fatty liver hepatitis and also hepatitis B. In conclusion, our results indicate that GSA‐I may aid in the detection of the subpopulation of activated macrophages which are assumed to play a pivotal role in liver pathology.
Chromatin Texture from Hematoxylin Stained Thyroid Lesions
Authors: Ferrer-Roca Olga , Pérez Gómez José A. , Estévez Maritza
Published: January 2015

Quantitative aspects of cytology and histology should be considered in diagnostic standardisation processes. The present paper summarises the cytological differences detected in 75 thyroid lesions using a computerized textural analysis.

Cells stained with progressive hematoxylin and taken from paraffin blocks were overlaid with the extracted texture. This technique was based on the lineal detection of a grey level gradient of the common logarithm of the integrated optical density (IOD) of each nucleus.

Diffuse and nodular goiters (36 cases) were demonstrated to be composed of small cells containing high density texture that, on microscopical visual inspection, gave a “salt and pepper” appearance. The adenomatous goiters (2 cases) and adenomas (26 cases) were composed of low texture cells with a visual “blurry or smudgy” chromatin, while the atypical adenomas with capsular invasion (4 cases) were characterised by a “woodworm” nuclear appearance that produced the highest texture of the series. Finally, encapsulated folliculo‐papillary carcinomas (3 cases) were composed of large clear nuclei with high IOD, low texture, and scattered lines that resulted in an “empty grape skin” aspect.

Our findings seam to confirm the suitability of computerized textural techniques that aid in recognizing cell microscopic features objectively. The one used in the present work, based on a mathematical function of the DNA content of each individual nucleus (IOD), fulfills all microscopy detection criteria.
A Review of Caveats in Statistical Nuclear Image Analysis
Authors: Schulerud Helene , Kristensen Gunner B. , Liestøl Knut , Vlatkovic Liljana , Reith Albrecht , Albregtsen Fritz , Danielsen Hàvard E.
Published: January 2015

A large body of the published literature in nuclear image analysis do not evaluate their findings on an independent data set. Hence, if several features are evaluated on a limited data set over‐optimistic results are easily achieved. In order to find features that separate different outcome classes of interest, statistical evaluation of the nuclear features must be performed. Furthermore, to classify an unknown sample using image analysis, a classification rule must be designed and evaluated. Unfortunately, statistical evaluation methods used in the literature of nuclear image analysis are often inappropriate. The present article discusses some of the difficulties in statistical evaluation of nuclear image analysis, and a study of cervical cancer is presented in order to illustrate the problems. In conclusion, some of the most severe errors in nuclear image analysis occur in analysis of a large feature set, including few patients, without confirming the results on an independent data set. To select features, Bonferroni correction for multiple test is recommended, together with a standard feature set selection method. Furthermore, we consider that the minimum requirement of performing statistical evaluation in nuclear image analysis is confirmation of the results on an independent data set. We suggest that a consensus of how to perform evaluation of diagnostic and prognostic features is necessary, in order to develop reliable tools for clinical use, based on nuclear image analysis.
Morphometric Measurements to Quantify the Cerulein Induced Hyperstimulatory Pancreatitis of Rats under the Protective Effect of Lectins
Authors: Jonas Ludwig , Mikkat Ulrike , Witte Anke , Beckmann Uta , Dölker Katrin , Weber Heike , Hahnel Christian , Kundt Günther , Nizze Horst
Published: January 2015

In preceding papers we demonstrated an inhibitory effect of wheat germ agglutinin (WGA) and Ulex europaeus agglutinin (UEA) on the cholecystokinin (CCK) binding to the CCK receptor of rat pancreatic cells and also on the CCK induced Ca2+ release and α‐amylase secretion in vitro as well as on pancreatic secretion of intact rats in vivo. In the present study we show the same inhibitory effect of both lectins on the cerulein pancreatitis of rats. This acute pancreatitis was induced by supramaximal injections (5 µg/kg/h iv or 10 µg/kg/h ip) of the CCK analogue cerulein in rats every hour. To monitor the degree of pancreatitis, we measured the number and diameter of injury vacuoles in the pancreatic acinar cells as one of the most important signs of this type of pancreatitis by light microscopic morphometry with two different systems on paraffin sections. Furthermore, the serum α‐amylase activity was measured biochemically. We found a correlation between the diameter of vacuoles inside the acinar cells and the serum enzyme activity up to 24 h. The simultaneous ip administration of cerulein and WGA or UEA in a dosage of 125 µg/kg/h for 8 h led to a reduction of vacuolar diameter from 13.1 ± 2.0 µm (cerulein) to 7.5 ± 1.1 µm (cerulein + WGA) or 7.2 ± 1.3 µm (cerulein + UEA). The serum amylase activity was reduced from 63.7 ± 15.8 mmol/l \times min (cerulein) to 37.7 ± 11.8 (cerulein + WGA) or 39.4; +52.9; ‐31.1 (cerulein + UEA‐I). Both parameters allow the grading this special type of pancreatitis to demonstrate the protective effect of the lectins.