bluuebunny/crossref_metadata_2025 huggingface dataset:
Implications of statistical power for confidence intervals
Authors: Liu Xiaofeng Steven
Published: October 2011

The statistical power of a hypothesis test is closely related to the precision of the accompanying confidence interval. In the case of a z‐test, the width of the confidence interval is a function of statistical power for the planned study. If minimum effect size is used in power analysis, the width of the confidence interval is the minimum effect size times a multiplicative factor φ. The index φ, or the precision‐to‐effect ratio, is a function of the computed statistical power. In the case of a t‐test, statistical power affects the probability of achieving a certain width of confidence interval, which is equivalent to the probability of obtaining a certain value of φ. To consider estimate precision in conjunction with statistical power, we can choose a sample size to obtain a desired probability of achieving a short width conditional on the rejection of the null hypothesis.
The energetic consequences of loop 9 gating motions in acetylcholine receptor‐channels
Authors: Jha Archana , Gupta Shaweta , Zucker Shoshanna N. , Auerbach Anthony
Published: October 2011

Non technical summary  Muscle cells have receptors that are activated by the neurotransmitter acetylcholine. The probability that these channels conduct ions across cell membranes increases dramatically when transmitter molecules are present at two binding sites, which are far from the region that regulates ionic conductance. In order to understand the molecular basis of receptor ‘gating’ we seek to learn how neurotransmitters and other small molecules activate this protein. We used single‐channel electrophysiology of receptors expressed in tissue‐cultured cells to study the effects of mutations at the C‐terminus of loop 9, a region near intra‐protein interfaces that are known to be important with regard to gating and assembly. We found that the mutation had modest but measurable effects on channel gating (mainly those in the epsilon subunit). We also found that mutations of loop 9 in the alpha subunit increase the kinetic heterogeneity of gating, which suggests that they alter the stability of the extracellular transmembrane domain interface.
Dual role of junctin in the regulation of ryanodine receptors and calcium release in cardiac ventricular myocytes
Authors: Altschafl Beth A. , Arvanitis Demetrios A. , Fuentes Oscar , Yuan Qunying , Kranias Evangelia G. , Valdivia Héctor H.
Published: October 2011

Non‐technical summary  Each heartbeat is accompanied by the coordinated release of calcium ions into cardiac cells through ryanodine receptors, which span the membrane of the sarcoplasmic reticulum. We show that an intra‐sarcoplasmic reticulum protein, junctin, interacts with ryanodine receptor channels and appears to activate them when calcium inside the sarcoplasmic reticulum is low. Conversely, junctin appears to act as an inhibitor of ryanodine receptors when calcium inside the sarcoplasmic reticulum is high. Knowledge of how junctin interacts with ryanodine receptors helps us to understand how calcium within the sarcoplasmic reticulum helps to regulate ryanodine receptor activity in normal hearts and also helps us to understand why junctin is decreased in patients diagnosed with certain forms of heart failure.
Carotid chemoreceptor modulation of blood flow during exercise in healthy humans
Authors: Stickland Michael K. , Fuhr Desi P. , Haykowsky Mark J. , Jones Kelvin E. , Paterson D. Ian , Ezekowitz Justin A. , McMurtry M. Sean
Published: October 2011

Non‐technical summary  Exercise causes an increase in sympathetic activity which helps to redistribute blood flow while maintaining blood pressure. The exact mechanisms that regulate sympathetic activity and blood flow during exercise are not completely understood. By modulating the activity of a specific chemical receptor (the carotid chemoreceptor), we showed that this receptor contributes to the regulation of blood flow during exercise in healthy subjects. These findings demonstrate the importance of the carotid chemoreceptor in the regulation of blood flow during exercise in health.
Potassium‐dependent activation of Kir4.2 K+ channels
Authors: Edvinsson Johan M. , Shah Anish J. , Palmer Lawrence G.
Published: October 2011

Non‐technical summary  The inwardly rectifying potassium channel, Kir4.2, is amongst the members of the Kir family of K+ channels whose activity is directly regulated by the external potassium concentration. We show here that, rather than increasing expression of the channel protein, this regulation is accomplished by activation of silent channels already present at the cell surface. Understanding the mechanism of this regulation will aid in understanding the physiological processes in which this subset of K+ channels is involved, such as regulation of blood pressure and control of neuronal excitability. It may also help to explain some of the consequences of hyperkalaemia, or excessive potassium, in blood plasma.
A Device to Study the Effects of Stretch Gradients on Cell Behavior
Authors: Richardson William J. , Metz Richard P. , Moreno Michael R. , Wilson Emily , Moore James E.
Published: October 2011

Mechanical forces are key regulators of cell function with varying loads capable of modulating behaviors such as alignment, migration, phenotype modulation, and others. Historically, cell-stretching experiments have employed mechanically simple environments (e.g., uniform uniaxial or equibiaxial stretches). However, stretch distributions in vivo can be highly non-uniform, particularly in cases of disease or subsequent to interventional treatments. Herein, we present a cell-stretching device capable of subjecting cells to controllable gradients in biaxial stretch via radial deformation of circular elastomeric membranes. By including either a defect or a rigid fixation at the center of the membrane, various gradients are generated. Capabilities of the device were quantified by tracking marked positions of the membrane while applying various loads, and experimental feasibility was assessed by conducting preliminary experiments with 3T3 fibroblasts and 10T1/2 cells subjected to 24 h of cyclic stretch. Quantitative real-time PCR was used to measure changes in mRNA expression of a profile of genes representing the major smooth muscle phenotypes. Genes associated with the contractile state were both upregulated (e.g., calponin) and downregulated (e.g., α-2-actin), and genes associated with the synthetic state were likewise both upregulated (e.g., SKI-like oncogene) and downregulated (e.g., collagen III). In addition, cells aligned with an orientation perpendicular to the maximal stretch direction. We have developed an in vitro cell culture device that can produce non-uniform stretch environments similar to in vivo mechanics. Cells stretched with this device showed alignment and altered mRNA expression indicative of phenotype modulation. Understanding these processes as they relate to in vivo pathologies could enable a more accurately targeted treatment to heal or inhibit disease, either through implantable device design or pharmaceutical approaches.
Elasticity of Human Embryonic Stem Cells as Determined by Atomic Force Microscopy
Authors: Kiss Robert , Bock Henry , Pells Steve , Canetta Elisabetta , Adya Ashok K. , Moore Andrew J. , De Sousa Paul , Willoughby Nicholas A.
Published: October 2011

The expansive growth and differentiation potential of human embryonic stem cells (hESCs) make them a promising source of cells for regenerative medicine. However, this promise is off set by the propensity for spontaneous or uncontrolled differentiation to result in heterogeneous cell populations. Cell elasticity has recently been shown to characterize particular cell phenotypes, with undifferentiated and differentiated cells sometimes showing significant differences in their elasticities. In this study, we determined the Young’s modulus of hESCs by atomic force microscopy using a pyramidal tip. Using this method we are able to take point measurements of elasticity at multiple locations on a single cell, allowing local variations due to cell structure to be identified. We found considerable differences in the elasticity of the analyzed hESCs, reflected by a broad range of Young’s modulus (0.05-10 kPa). This surprisingly high variation suggests that elasticity could serve as the basis of a simple and efficient large scale purification/separation technique to discriminate subpopulations of hESCs.
Deterioration of Bone Quality in the Tibia and Fibula in Growing Mice During Skeletal Unloading: Gender-Related Differences
Authors: Ko Chang-Yong , Hyun Seo Dong , Sung Kim Han
Published: October 2011

Skeletal unloading causes bone loss in both men and women; however, only a few studies have been performed on the effects of gender differences on bone quality during skeletal unloading. Moreover, although the fibula also plays an important role in load bearing and ankle stability, the effects of unloading on the fibula have been rarely investigated. The present study aimed to investigate the effects of skeletal unloading on bone quality of the tibia and fibula in growing animals and to determine whether differences existed between genders. Six-week-old female and male mice were randomly allocated into two groups. The right hindlimb of each mouse in the skeletal unloading group was subjected to sciatic neurectomy. After two weeks of skeletal unloading, the structural characteristics of the tibia and fibula in both genders were worsened. In addition, the bone mineralization density distribution (MDD) of the tibia and fibula in both genders were altered. However, the magnitude of deterioration and alteration of the MDD in the bones of females were larger than in those of males. These results demonstrate that skeletal unloading diminishes bone quality in the tibia and fibula, leading to an increase in bone fracture risks, particularly in females.
Plasma and vacuum ultraviolet induced charging of SiO2 and HfO2 patterned structures
Authors: Lauer J. L. , Upadhyaya G. S. , Sinha H. , Kruger J. B. , Nishi Y. , Shohet J. L.
Published: October 2011

The authors compare the effects of plasma charging and vacuum ultraviolet (VUV) irradiation on oxidized patterned Si structures with and without atomic-layer-deposited HfO2. It was found that, unlike planar oxidized Si wafers, oxidized patterned Si wafers charge up significantly after exposure in an electron-cyclotron resonance plasma. The charging is dependent on the aspect ratio of the patterned structures. This is attributed to electron and/or ion shading during plasma exposure. The addition of a 10 nm thick HfO2 layer deposited on top of the oxidized silicon structures increases the photoemission yield during VUV irradiation, resulting in more trapped positive charge compared to patterns without the HfO2 dielectric.
LaMnO3: Influence of the Addition of Ba and Sr
Authors: Glisenti Antonella , Galenda Alessandro , Natile Marta Maria
Published: October 2011

The present work focuses on lanthanum manganite-based materials obtained by citrate (LaMnO3 and La0.6Sr0.4MnO3) and Pechini (La0.6Ba0.4MnO3) methods. The influence of the addition of barium and strontium is studied. The surface properties of LaMnO3, La0.6Ba0.4MnO3 and La0.6Sr0.4MnO3 powders are investigated by means of XPS using a standard Al Kα source. Besides the wide scan spectra, detailed spectra for the La 3d, Mn 2p, O 1s, Sr 3d and Ba 3d regions and related data are presented and discussed.
Bound by Oxygen
Authors: Wong Wei
Published: October 2011

A dioxygenase binds to and inhibits a hypoxia-inducible transcription factor in the presence of oxygen.
Poised by Noise
Authors: VanHook Annalisa M.
Published: October 2011

A stochastically activated genetic circuit enables bacteria to respond to stress.
Efficacy, Safety, and Pharmacokinetics of Intravenous Peramivir in Children with 2009 Pandemic H1N1 Influenza A Virus Infection
Authors: Sugaya Norio , Kohno Shigeru , Ishibashi Toru , Wajima Toshihiro , Takahashi Takao
Published: October 2011

Peramivir is a new neuraminidase inhibitor for intravenous administration that was first introduced in clinical practice in Japan. We conducted a multicenter, open-label, uncontrolled study in children with influenza virus infection ranging in age from ≥28 days to <16 years during the 2009 pandemic A (H1N1) influenza epidemic to evaluate the efficacy, safety, and pharmacokinetics of peramivir in children after intravenous infusion of 10 mg/kg (600 mg maximum) once daily. Among the 106 children (125 days to 15 years old) confirmed to have been infected with the pH1N1 virus by the PCR who were treated with peramivir, the median time to alleviation of symptoms was 29.1 h (95% confidence interval = 22.1 to 32.4), and the proportion of the 106 children who were virus positive was 78.2% on day 2 after the start of treatment and had decreased to 7.1% on day 6. The results of the safety evaluation among 117 patients enrolled in this study showed that adverse events and adverse drug reactions were reported in 62.4 and 29.1%, respectively, of the patients. All of the adverse events and adverse drug reactions resolved or improved rapidly. A population pharmacokinetic analysis was performed on the basis of 297 observed plasma concentration data obtained from 115 children with influenza virus infection. Peramivir exposure in children was within the range of levels within which the efficacy and safety was confirmed in adults, and it is considered that peramivir is clinically and virologically effective and safe in children with pH1N1 virus infection.
Antifungal Susceptibilities of Aspergillus fumigatus Clinical Isolates Obtained in Nagasaki, Japan
Authors: Tashiro Masato , Izumikawa Koichi , Minematsu Asuka , Hirano Katsuji , Iwanaga Naoki , Ide Shotaro , Mihara Tomo , Hosogaya Naoki , Takazono Takahiro , Morinaga Yoshitomo , Nakamura Shigeki , Kurihara Shintaro , Imamura Yoshifumi , Miyazaki Taiga , Nishino Tomoya , Tsukamoto Misuzu , Kakeya Hiroshi , Yamamoto Yoshihiro , Yanagihara Katsunori , Yasuoka Akira , Tashiro Takayoshi , Kohno Shigeru
Published: October 2011

We investigated the triazole, amphotericin B, and micafungin susceptibilities of 196
A. fumigatus
clinical isolates in Nagasaki, Japan. The percentages of non-wild-type (non-WT) isolates for which MICs of itraconazole, posaconazole, and voriconazole were above the ECV were 7.1%, 2.6%, and 4.1%, respectively. A G54 mutation in
cyp51A
was detected in 64.2% (9/14 isolates) and 100% (5/5 isolates) of non-WT isolates for itraconazole and posaconazole, respectively. Amphotericin B MICs of ≥2 μg/ml and micafungin minimum effective concentrations (MECs) of ≥16 μg/ml were recorded for two and one isolates, respectively.
Novel Protein-Based Pneumococcal Vaccines Administered with the Th1-Promoting Adjuvant IC31 Induce Protective Immunity against Pneumococcal Disease in Neonatal Mice
Authors: Olafsdottir Thorunn Asta , Lingnau Karen , Nagy Eszter , Jonsdottir Ingileif
Published: October 2011

Streptococcus pneumoniae
is responsible for many vaccine-preventable deaths, annually causing around 1 million deaths in children younger than 5 years of age. A new generation of pneumococcal vaccines based on conserved proteins is being developed. We evaluated the immunogenicities and protective efficacies of four pneumococcal protein vaccine candidates, PcsB, StkP, PsaA, and PspA, in a neonatal mouse model. Mice were immunized three times and challenged intranasally with virulent pneumococci. All four proteins were immunogenic in neonatal mice, and antibody (Ab) responses were significantly enhanced by the novel adjuvant IC31, which consists of an antibacterial peptide (

KLKL
5
KLK

) and a synthetic oligodeoxynucleotide, ODN1a, that signals through Toll-like receptor 9 (TLR9). Two single proteins, StkP and PspA, combined with IC31 significantly reduced pneumococcal bacteremia but had no effects on lung infection. Three proteins, PcsB, StkP, and PsaA, were evaluated with alum or IC31. IC31 enhanced Ab responses and avidity to all three proteins, whereas alum enhanced Ab responses and avidity to StkP and PsaA only. Mice receiving the trivalent protein formulation with IC31 had significantly reduced bacteremia and lung infection compared to unvaccinated mice, but the level of protection was dependent on the dose of IC31. When PspA was added to the trivalent protein formulation, the dose of IC31 needed to obtain protective immunity could be reduced. These results demonstrate that a novel pneumococcal protein-based vaccine is immunogenic at an early age of mice and emphasize the benefits of using a combination of conserved proteins and an effective adjuvant to elicit potent protective immunity against invasive pneumococcal disease.
Conserved Regions as Markers of Different Patterns of Expression and Distribution of the Mucin-Associated Surface Proteins of Trypanosoma cruzi
Authors: De Pablos Luis M. , Osuna Antonio
Published: October 2011

The MASP gene family is the second most widely represented gene family in the genome of
Trypanosoma cruzi
. One of its main characteristics is that its 5′ and 3′ regions are highly conserved. We assessed the expression of these conserved regions as a marker for
T. cruzi
and also analyzed the expression of the
masp
genes and MASP proteins. In parasite strains CL-Brener (DTUVI lineage) and PAN4 (DTUI lineage),
masp
genes were expressed at different levels both with regard to the two strains and between stages in the parasite's life cycle. We also studied the expression of the family during the intracellular cycle of
T. cruzi
, using antibodies against the conserved MASP signal peptide (SP). Fluorescence intensity showed an increase in expression from 24 h onwards, with a peak in intensity at 72 h postinfection. After 24 and 48 h, the MASP proteins were expressed in 33.33% and 57.14% of the amastigotes, respectively. Our data show that not only the extracellular forms of
T. cruzi
but also the intracellular phases express this type of protein, though to different extents in the various forms of the parasite.
Differential Role of the Interleukin-17 Axis and Neutrophils in Resolution of Inhalational Anthrax
Authors: Garraud Kévin , Cleret Aurélie , Mathieu Jacques , Fiole Daniel , Gauthier Yves , Quesnel-Hellmann Anne , Tournier Jean-Nicolas
Published: October 2011

The roles of interleukin-17 (IL-17) and neutrophils in the lung have been described as those of two intricate but independent players. Here we identify neutrophils as the primary IL-17-secreting subset of cells in a model of inhalation anthrax using A/J and C57BL/6 mice. With IL-17 receptor A knockout (IL-17RA
−/−
) mice, we confirmed that IL-17A/F signaling is instrumental in the self-recruitment of this population. We also show that the IL-17A/F axis is critical for surviving pulmonary infection, as IL-17RA
−/−
mice become susceptible to intranasal infection by
Bacillus anthracis
Sterne spores. Strikingly, infection with a fully virulent strain did not affect IL-17RA
−/−
mouse survival. Eventually, by depleting neutrophils in wild-type and IL-17RA
−/−
mice, we demonstrated the crucial role of IL-17-secreting neutrophils in mouse survival of infection by fully virulent
B. anthracis
. This work demonstrates the important roles of both IL-17 signaling and neutrophils in clearing this pathogen and surviving pulmonary
B. anthracis
infection.
TWO NEW PHASE-FITTED SYMPLECTIC PARTITIONED RUNGE–KUTTA METHODS
Authors: MONOVASILIS TH. , KALOGIRATOU Z. , SIMOS T. E.
Published: October 2011

New symplectic Partitioned Runge–Kutta (SPRK) methods with phase-lag of order infinity are derived in this paper. Specifically two new symplectic methods are constructed with second and third algebraic order. The methods are tested on the numerical integration of Hamiltonian problems and on the estimation of the eigenvalues of the Schrödinger equation.
STUDY OF DISCRETE GLOBAL-SLIDING MODE CONTROL FOR SWITCHING DC-DC CONVERTER
Authors: NI YU , XU JIANPING
Published: October 2011

Discrete global-sliding mode (SM) control of switching DC-DC converters is presented in this paper. The existence and stability conditions of quasi global-sliding mode are proposed. The design method for the discrete global SM controller is studied and applied to Buck converter with global-sliding mode control. Computer simulation and experimental results verify the validity of the theoretical analysis.
MULTISTAGE MUTUAL INFORMATION FOR INFORMATIVE GENE SELECTION
Authors: GANESH KUMAR P. , ARULDOSS ALBERT VICTOIRE T.
Published: October 2011

An important issue in the design of gene selection algorithm for microarray data analysis is the formation of suitable criterion function for measuring the relevance between different gene expressions. Mutual information (MI) is a widely used criterion function but it calculates the relevance on the entire samples only once which cannot exactly identify the informative genes. This paper proposes a novel idea of computing MI in stages. The proposed multistage mutual information (MSMI) computes MI, initially using all the samples and based on the classification performance produced by artificial neural network (ANN), MI is repeatedly calculated using only the unclassified samples until there is no improvement in the classification accuracy. The performance of the proposed approach is evaluated using ten gene expression data sets. Simulation result shows that the proposed approach helps to improve the discriminate power of the genes with regard to the target disease of a microarray sample. Statistical analysis of the test result shows that the proposed method selects highly informative genes and produces comparable classification accuracy than the other approaches reported in the literature.
Resource-constrained multiprocessor synthesis for floating-point applications on FPGAs
Authors: Wang Xiaofang , Gupta Pallav
Published: October 2011

Although state-of-the-art field-programmable gate arrays offer exciting new opportunities in exploring low-cost high-performance architectures for data-intensive scientific applications, they also present serious challenges. Multiprocessor-on-programmable-chip, which integrates software programmability and hardware reconfiguration, provides substantial flexibility that results in shorter design cycles, higher performance, and lower cost. In this article, we present an application-specific design methodology for multiprocessor-on-programmable-chip architectures that target applications involving large matrices and floating-point operations. Given an application with specific energy-performance and resource constraints, our methodology aims to customize the architecture to match the diverse computation and communication requirements of the application tasks. Graph-based analysis of the application drives system synthesis that employs a precharacterized, parameterized hardware component library of functional units. Extensive experimental results for three diverse applications are presented to demonstrate the efficacy of our design methodology.
Mitigating the effects of large multiple cell upsets (MCUs) in memories
Authors: Maestro Juan Antonio , Reviriego Pedro , Baeg Sanghyeon , Wen Shijie , Wong Richard
Published: October 2011

Reliability is a critical issue for memories. Radiation particles that hit the device can cause errors in some cells, which can lead to data corruption. To avoid this problem, memories are protected with per-word error correction codes (ECCs). Typically, single-error correction and double-error detection (SEC-DED) codes are used. As technology scales, errors caused by radiation particles on memories tend to affect more than one cell—what is known as a multiple cell upset (MCU). To ensure that only a single cell is affected in each word, interleaving is used. With interleaving, cells that belong to the same word are placed at a sufficient distance such that an MCU will only affect a single cell on each word. The use of interleaving significantly increases the cost of the device. Also, determining the interleaving distance (ID) required to avoid MCUs causing double errors is not trivial. Typically, accelerated radiation experiments with a limited number of particle hits are used. They provide a lower bound on the required ID, but larger MCUs may occur with a low probability. But even if the percentage of such large MCUs is very low, the impact on reliability can be significant. This article presents a technique to mitigate the effects of large MCUs that is, those that exceed the ID, on memory reliability. The proposed approach is able to correct most double errors caused by large MCUs by exploiting the locality of the errors within an MCU.
A 36μW heartbeat-detection processor for a wireless sensor node
Authors: Duarte Filipa , Hulzink Jos , Zhou Jun , Stuijt Jan , Huisken Jos , De Groot Harmke
Published: October 2011

In order to provide better services to elderly people, home healthcare monitoring systems have been increasingly deployed. Typically, these systems are based on wireless sensor nodes, and should utilize very low energy during their lifetimes, as they are powered by scavengers. In this article, we present an ultra-low power processing system for a wireless sensor node for very low duty cycle applications. In the CoolBio system-on-chip, we utilized several power reduction techniques at both the architecture level and the circuit level. These techniques include feature extraction, voltage and frequency scaling, clock and power gating and a redesign of key standard cells. In the design of the ultra-low power processing system, we paid special attention to the memory subsystem, as it is one of the most power-consuming modules in a design. We also designed a clock manager in order to reduce the power consumed by clocking, and a power manager that is able to power-off unutilized modules. The proposed wireless sensor node processing system consumes 36.4μW at 100MHz and 1.2V supply voltage, for a heartbeat-detection algorithm with a 0.01% duty cycle.
In the Virtual Extension
Authors: CACM Staff
Published: October 2011

To ensure the timely publication of articles,
Communications
created the Virtual Extension (VE) to expand the page limitations of the print edition by bringing readers the same high-quality articles in an online-only format. VE articles undergo the same rigorous review process as those in the print edition and are accepted for publication on merit. The following synopses are from articles now available in their entirety to ACM members via the Digital Library.
Risky business
Authors: Hoffmann Leah
Published: October 2011

Governments, companies, and individuals have suffered an unusual number of highly publicized data breaches this year. Is there a solution?
Teaching-oriented faculty at research universities
Authors: SIGCSE Teaching-Oriented Faculty Working Group
Published: October 2011

Developing a well-rounded university through specialization.
Puzzled: Distances between points on the plane
Authors: Winkler Peter
Published: October 2011

Welcome to three new puzzles. Solutions to the first two will be published next month; the third is as yet (famously) unsolved.
Toric degenerations of Bézier patches
Authors: Garc'ia-Puente Luis David , Sottile Frank , Zhu Chungang
Published: October 2011

The control polygon of a rational Bézier curve is well-defined and has geometric significance; there is a sequence of weights under which the limiting position of the curve is the control polygon. For a rational Bézier surface patch, there are many possible polyhedral control structures, and none is canonical. We propose a not necessarily polyhedral control structure for rational surface patches, regular control surfaces, which are certain
C
0
spline surfaces. While not unique, regular control surfaces are exactly the possible limiting positions of a rational Bézier patch when the weights vary.
Robust adaptive photon tracing using photon path visibility
Authors: Hachisuka Toshiya , Jensen Henrik Wann
Published: October 2011

We present a new adaptive photon tracing algorithm which can handle illumination settings that are considered difficult for photon tracing approaches such as outdoor scenes, close-ups of a small part of an illuminated region, and illumination coming through a small gap. The key contribution in our algorithm is the use of visibility of photon path as the importance function which ensures that our sampling algorithm focuses on paths that are visible from the given viewpoint. Our sampling algorithm builds on two recent developments in Markov chain Monte Carlo methods: adaptive Markov chain sampling and replica exchange. Using these techniques, each photon path is adaptively mutated and it explores the sampling space efficiently without being stuck at a local peak of the importance function. We have implemented this sampling approach in the progressive photon mapping algorithm which provides visibility information in a natural way when a photon path contributes to a measurement point. We demonstrate that the final algorithm is strikingly simple, yet effective at sampling photons under lighting conditions that would be difficult for existing Monte Carlo ray tracing-based methods.
Razor
Authors: Djeu Peter , Hunt Warren , Wang Rui , Elhassan Ikrima , Stoll Gordon , Mark William R.
Published: October 2011

Recent work demonstrates that interactive ray tracing is possible on desktop systems, but there is still much debate as to how to most efficiently support advanced visual effects such as soft shadows, smooth freeform surfaces, complex shading, and animated scenes. With these challenges in mind, we reconsider the options for designing a rendering system and present
Razor
, a new software rendering architecture for distribution ray tracing designed to produce high-quality images with high performance on future single-chip many-core hardware. Razor includes two noteworthy capabilities: a set of techniques for quickly building the kd-tree acceleration structure on demand every frame from a scene graph and a system design that allows for crack-free multiresolution geometry with each ray independently choosing its geometry resolution. Razor's per-frame kd-tree build is designed to robustly handle arbitrarily scene animation, while its per-ray multiresolution geometry provides continuous level of detail driven by ray and path differentials. Razor also decouples shading from visibility computations using a two-phase shading scheme inspired by the REYES system, and caches tessellated representations of freeform surfaces at multiple levels of detail.

We present experimental results gathered from a prototype system implemented on eight CPU cores, and discuss which aspects of the system are most successful and which would benefit from further investigation.
A Framework for content-adaptive photo manipulation macros
Authors: Berthouzoz Floraine , Li Wilmot , Dontcheva Mira , Agrawala Maneesh
Published: October 2011

We present a framework for generating content-adaptive macros that can transfer complex photo manipulations to new target images. We demonstrate applications of our framework to face, landscape, and global manipulations. To create a content-adaptive macro, we make use of multiple training demonstrations. Specifically, we use automated image labeling and machine learning techniques to learn the dependencies between image features and the parameters of each selection, brush stroke, and image processing operation in the macro. Although our approach is limited to learning manipulations where there is a direct dependency between image features and operation parameters, we show that our framework is able to learn a large class of the most commonly used manipulations using as few as 20 training demonstrations. Our framework also provides interactive controls to help macro authors and users generate training demonstrations and correct errors due to incorrect labeling or poor parameter estimation. We ask viewers to compare images generated using our content-adaptive macros with and without corrections to manually generated ground-truth images and find that they consistently rate both our automatic and corrected results as close in appearance to the ground truth. We also evaluate the utility of our proposed macro generation workflow via a small informal lab study with professional photographers. The study suggests that our workflow is effective and practical in the context of real-world photo editing.
Fast simulation of skeleton-driven deformable body characters
Authors: Kim Junggon , Pollard Nancy S.
Published: October 2011

We propose a fast physically-based simulation system for skeleton-driven deformable body characters. Our system can generate realistic motions of self-propelled deformable body characters by considering the two-way interactions among the skeleton, the deformable body, and the environment in the dynamic simulation. It can also compute the passive jiggling behavior of a deformable body driven by a kinematic skeletal motion. We show that a well-coordinated combination of: (1) a reduced deformable body model with nonlinear finite elements, (2) a linear-time algorithm for skeleton dynamics, and (3) explicit integration can boost simulation speed to orders of magnitude faster than existing methods, while preserving modeling accuracy as much as possible. Parallel computation on the GPU has also been implemented to obtain an additional speedup for complicated characters. Detailed discussions of our engineering decisions for speed and accuracy of the simulation system are presented in the article. We tested our approach with a variety of skeleton-driven deformable body characters, and the tested characters were simulated in real time or near real time.
Fast oriented bounding box optimization on the rotation group
SO
(3,ℝ)
Authors: Chang Chia-Tche , Gorissen Bastien , Melchior Samuel
Published: October 2011

An exact algorithm to compute an optimal 3D oriented bounding box was published in 1985 by Joseph O'Rourke, but it is slow and extremely hard to implement. In this article we propose a new approach, where the computation of the minimal-volume OBB is formulated as an unconstrained optimization problem on the rotation group
SO
(3,ℝ). It is solved using a hybrid method combining the genetic and Nelder-Mead algorithms. This method is analyzed and then compared to the current state-of-the-art techniques. It is shown to be either faster or more reliable for any accuracy.
A Specialized Search Assistant for Learning Objects
Authors: Curlango-Rosas Cecilia , Ponce Gregorio A. , Lopez-Morteo Gabriel A.
Published: October 2011

The Web holds a great quantity of material that can be used to enhance classroom instruction. However, it is not easy to retrieve this material with the search engines currently available. This study produced a specialized search assistant based on Google that significantly increases the number of instances in which teachers find the desired learning objects as compared to using this popular public search engine directly. Success in finding learning objects by study participants went from 80% using Google alone to 96% when using our search assistant in one scenario and, in another scenario, from a 40% success rate with Google alone to 66% with our assistant. This specialized search assistant implements features such as bilingual search and term suggestion which were requested by teacher participants to help improve their searches. Study participants evaluated the specialized search assistant and found it significantly easier to use and more useful than the popular search engine for the purpose of finding learning objects.
A Hybrid Approach to Failed Disk Recovery Using RAID-6 Codes
Authors: Xiang Liping , Xu Yinlong , Lui John C. S. , Chang Qian , Pan Yubiao , Li Runhui
Published: October 2011

The current parallel storage systems use thousands of inexpensive disks to meet the storage requirement of applications. Data redundancy and/or coding are used to enhance data availability, for instance, Row-diagonal parity (RDP) and EVENODD codes, which are widely used in RAID-6 storage systems, provide data availability with up to
two disk failures
. To reduce the probability of data unavailability, whenever a single disk fails, disk recovery will be carried out. We find that the conventional recovery schemes of RDP and EVENODD codes for a single failed disk only use one parity disk. However, there are two parity disks in the system, and both can be used for single disk failure recovery. In this article, we propose a hybrid recovery approach that uses both parities for single disk failure recovery, and we design efficient recovery schemes for RDP code (RDOR-RDP) and EVENODD code (RDOR-EVENODD). Our recovery scheme has the following attractive properties: (1) “
read optimality
” in the sense that our scheme issues the smallest number of disk reads to recover a single failed disk and it reduces approximately 1/4 of disk reads compared with conventional schemes; (2) “
load balancing property
” in that all surviving disks will be subjected to the same (or almost the same) amount of additional workload in rebuilding the failed disk.

We carry out performance evaluation to quantify the merits of RDOR-RDP and RDOR-EVENODD on some widely used disks with DiskSim. The offline experimental results show that RDOR-RDP and RDOR-EVENODD outperform the conventional recovery schemes of RDP and EVENODD codes in terms of total recovery time and recovery workload on individual surviving disk. However, the improvements are less than the theoretical value (approximately 25%), as RDOR-RDP and RDOR-EVENODD change the disk access pattern from purely sequential to a more random one compared with their conventional schemes.
Toward 3D Integration of 1D Conductors: Junctions of InAs Nanowires
Authors: Wu Phillip M. , Samuelson Lars , Linke Heiner
Published: October 2011

A vision and one of the next challenges in nanoelectronics is the 3D integration of nanowire building blocks. Here we show that capillary forces associated with a liquid-air meniscus between two nanowires provides a simple, controllable technique to bend vertical nanowires into designed, interconnected assemblies. We characterize the electric nature of the junctions between crossed nanowires in a lateral geometry, which is one type of basic unit that can be found in interconnected-bent vertical nanowires. The crossed nanowire junction is capacitive in nature, and we demonstrate that one nanowire can be used to field effect gate the other nanowire, allowing for the possibility to develop extremely narrow conducting channels in nanowire planar or 3D electronic devices.
On the Minimal Length Uncertainty Relation and the Foundations of String Theory
Authors: Chang Lay Nam , Lewis Zachary , Minic Djordje , Takeuchi Tatsu
Published: October 2011

We review our work on the minimal length uncertainty relation as suggested by perturbative string theory. We discuss simple phenomenological implications of the minimal length uncertainty relation and then argue that the combination of the principles of quantum theory and general relativity allow for a dynamical energy-momentum space. We discuss the implication of this for the problem of vacuum energy and the foundations of nonperturbative string theory.
Alpha 1,3‐Galactosyltransferase Deficiency in Pigs Increases Sialyltransferase Activities That Potentially Raise Non‐Gal Xenoantigenicity
Authors: Park Jong-Yi , Park Mi-Ryung , Kwon Deug-Nam , Kang Min-Hui , Oh Mihye , Han Jae-Woong , Cho Ssang-Goo , Park Chankyu , Kim Dong-Ku , Song Hyuk , Oh Jae-Wook , Kim Jin-Hoi
Published: October 2011

We examined whether deficiency of the GGTA1 gene in pigs altered the expression of several glycosyltransferase genes. Real‐time RT‐PCR and glycosyltransferase activity showed that 2 sialyltransferases [α2,3‐sialyltransferase (α2,3ST) and α2,6‐sialyltransferase (α2,6ST)] in the heterozygote GalT KO liver have higher expression levels and activities compared to controls. Enzyme‐linked lectin assays indicated that there were also more sialic acid‐containing glycoconjugate epitopes in GalT KO livers than in controls. The elevated level of sialic‐acid‐containing glycoconjugate epitopes was due to the low level of α‐Gal in heterozygote GalT KO livers. Furthermore, proteomics analysis showed that heterozygote GalT KO pigs had a higher expression of NAD+‐isocitrate dehydrogenase (IDH), which is related to the CMP‐N‐acetylneuraminic acid hydroxylase (CMAH) enzyme reaction. These findings suggest the deficiency of GGTA1 gene in pigs results in increased production of N‐glycolylneuraminic acid (Neu5Gc) due to an increase of α2,6‐sialyltransferase and a CMAH cofactor, NAD+‐IDH. This indicates that Neu5Gc may be a critical xenoantigen. The deletion of the CMAH gene in the GalT KO background is expected to further prolong xenograft survival.
Panel Unit Root Tests by Combining Dependent P Values: A Comparative Study
Authors: Sheng Xuguang , Yang Jingyun
Published: October 2011

We conduct a systematic comparison of the performance of four commonly used P value combination methods applied to panel unit root tests: the original Fisher test, the modified inverse normal method, Simes test, and the modified truncated product method (TPM). Our simulation results show that under cross‐section dependence the original Fisher test is severely oversized, but the other three tests exhibit good size properties. Simes test is powerful when the total evidence against the joint null hypothesis is concentrated in one or very few of the tests being combined, but the modified inverse normal method and the modified TPM have good performance when evidence against the joint null is spread among more than a small fraction of the panel units. These differences are further illustrated through one empirical example on testing purchasing power parity using a panel of OECD quarterly real exchange rates.
The Influence of 3′UTRs on MicroRNA Function Inferred from Human SNP Data
Authors: Hu Zihua , Bruno Andrew E.
Published: October 2011

MicroRNAs (miRNAs) regulate gene expression posttranscriptionally. Although previous efforts have demonstrated the functional importance of target sites on miRNAs, little is known about the influence of the rest of 3′ untranslated regions (3′UTRs) of target genes on microRNA function. We conducted a genome-wide study and found that the entire 3′UTR sequences could also play important roles on miRNA function in addition to miRNA target sites. This was evidenced by the fact that human single nucleotide polymorphisms (SNPs) on both seed target region and the rest of 3′UTRs of miRNA target genes were under significantly stronger negative selection, when compared to non-miRNA target genes. We also discovered that the flanking nucleotides on both sides of miRNA target sites were subject to moderate strong selection. A local sequence region of ~67 nucleotides with symmetric structure is herein defined. Additionally, from gene expression analysis, we found that SNPs and miRNA target sites on target sequences may interactively affect gene expression.
Selectin Ligand Sialyl-Lewis x Antigen Drives Metastasis of Hormone-Dependent Breast Cancers
Authors: Julien Sylvain , Ivetic Aleksandar , Grigoriadis Anita , QiZe Ding , Burford Brian , Sproviero Daisy , Picco Gianfranco , Gillett Cheryl , Papp Suzanne L. , Schaffer Lana , Tutt Andrew , Taylor-Papadimitriou Joyce , Pinder Sarah E. , Burchell Joy M.
Published: October 2011

The glycome acts as an essential interface between cells and the surrounding microenvironment. However, changes in glycosylation occur in nearly all breast cancers, which can alter this interaction. Here, we report that profiles of glycosylation vary between ER-positive and ER-negative breast cancers. We found that genes involved in the synthesis of sialyl-Lewis x (sLex; FUT3, FUT4, and ST3GAL6) are significantly increased in estrogen receptor alpha-negative (ER-negative) tumors compared with ER-positive ones. SLex expression had no influence on the survival of patients whether they had ER-negative or ER-positive tumors. However, high expression of sLex in ER-positive tumors was correlated with metastasis to the bone where sLex receptor E-selectin is constitutively expressed. The ER-positive ZR-75-1 and the ER-negative BT20 cell lines both express sLex but only ZR-75-1 cells could adhere to activated endothelial cells under dynamic flow conditions in a sLex and E-selectin–dependent manner. Moreover, L/P-selectins bound strongly to ER-negative MDA-MB-231 and BT-20 cell lines in a heparan sulfate (HS)–dependent manner that was independent of sLex expression. Expression of glycosylation genes involved in heparan biosynthesis (EXT1 and HS3ST1) was increased in ER-negative tumors. Taken together, our results suggest that the context of sLex expression is important in determining its functional significance and that selectins may promote metastasis in breast cancer through protein-associated sLex and HS glycosaminoglycans. Cancer Res; 71(24); 7683–93. ©2011 AACR.
PGE2-Induced CXCL12 Production and CXCR4 Expression Controls the Accumulation of Human MDSCs in Ovarian Cancer Environment
Authors: Obermajer Nataša , Muthuswamy Ravikumar , Odunsi Kunle , Edwards Robert P. , Kalinski Pawel
Published: October 2011

Signals mediated by CXCL12 (SDF1) and its receptor CXCR4 are centrally involved in cancer progression, both directly by activating cancer cells and indirectly by inducing angiogenesis plus recruiting T regulatory and plasmacytoid dendritic immune cells. Here, we show that in ascites isolated from ovarian cancer patients, both CXCL12 and CXCR4 are controlled by the tumor-associated inflammatory mediator prostaglandin E2 (PGE2), which attracts myeloid-derived suppressor cells (MDSC) into the ascites microenvironment. In this setting, PGE2 was essential both for expression of functional CXCR4 in cancer-associated MDSCs and for production of its ligand CXCL12. Frequencies of CD11b+CD14+CD33+CXCR4+ MDSCs closely correlated with CXCL12 and PGE2 levels in patient ascites. MDSCs migrated toward ovarian cancer ascites in a CXCR4-dependent manner that required COX2 activity and autocrine PGE2 production. Inhibition of COX2 or the PGE2 receptors EP2/EP4 in MDSCs suppressed expression of CXCR4 and MDSC responsiveness to CXCL12 or ovarian cancer ascites. Similarly, COX2 inhibition also blocked CXCL12 production in the ovarian cancer environment and its ability to attract MDSCs. Together, our findings elucidate a central role for PGE2 in MDSC accumulation triggered by the CXCL12-CXCR4 pathway, providing a powerful rationale to target PGE2 signaling in ovarian cancer therapy. Cancer Res; 71(24); 7463–70. ©2011 AACR.
Eligibility, Compliance and Persistence of Sequential Therapy with Aromatase Inhibitors following 2–3 Years of Tamoxifen in Endocrine Adjuvant Breast Cancer Therapy
Authors: Kilic Nerbil , Myrick Mary Elizabeth , Schmid Seraina Margaretha , Gueth Uwe
Published: October 2011

Objective: This study evaluated the eligibility, compliance and persistence of sequential therapy, i.e. a switch to an aromatase inhibitor (AI) following 2–3 years of tamoxifen, in adjuvant endocrine breast cancer (BC) treatment. Methods: Data concerning 388 BC patients (age ≤70 years) who started endocrine adjuvant therapy between 1998 and 2008 were analyzed. Results: From the 263 patients who started therapy with tamoxifen, 167 (63.5%) were eligible for a sequential therapy. Fifty-nine patients (35.3%) were offered a switch by their physicians; women who had their follow-up at oncological units received the offer more often when compared to those treated by general practitioners (p < 0.001). Out of these 59 patients, 50 followed the proposal (compliance 84.7%). Of those who agreed to a sequential therapy, 2 (4%) were non-persistent to endocrine therapy; in 9 cases (18.0%), a re-switch to tamoxifen was done due to AI-related adverse side effects. Conclusions: Only a minority of the patients who started an endocrine adjuvant BC therapy was eligible for sequential therapy. Patients who underwent a switch had a high rate of persistence. Efforts should be made to make sure that all physicians, above all general practitioners, who are involved in the treatment of BC patients, are provided with current therapy guidelines.