bluuebunny/crossref_metadata_2025 huggingface dataset:
INTELLECTUAL PROPERTY RIGHTS, INSTITUTIONAL QUALITY AND ECONOMIC GROWTH
Authors: DAVIS LEWIS S. , ŞENER FUAT
Published: February 2012

We consider intellectual property rights (IPRs) in a Schumpeterian growth model in which patent holders face the threats of profit loss due to imitation and complete valuation loss due to outside innovation. We disaggregate IPR policies by distinguishing between the quality of the IPR regime and the intensity of IPR enforcement. An increase in the quality of the IPR regime unambiguously promotes growth. However, the relationship between IPR enforcement intensity and growth follows an inverted U-shaped curve. The growth-maximizing intensity of IPR enforcement is decreasing in institutional quality. We also investigate the model's welfare implications and examine the economy under a no-growth equilibrium.
Physically-based simulation of rainbows
Authors: Sadeghi Iman , Munoz Adolfo , Laven Philip , Jarosz Wojciech , Seron Francisco , Gutierrez Diego , Jensen Henrik Wann
Published: February 2012

In this article, we derive a physically-based model for simulating rainbows. Previous techniques for simulating rainbows have used either geometric optics (ray tracing) or Lorenz-Mie theory. Lorenz-Mie theory is by far the most accurate technique as it takes into account optical effects such as dispersion, polarization, interference, and diffraction. These effects are critical for simulating rainbows accurately. However, as Lorenz-Mie theory is restricted to scattering by spherical particles, it cannot be applied to real raindrops which are nonspherical, especially for larger raindrops. We present the first comprehensive technique for simulating the interaction of a wavefront of light with a physically-based water drop shape. Our technique is based on ray tracing extended to account for dispersion, polarization, interference, and diffraction. Our model matches Lorenz-Mie theory for spherical particles, but it also enables the accurate simulation of nonspherical particles. It can simulate many different rainbow phenomena including double rainbows and supernumerary bows. We show how the nonspherical raindrops influence the shape of the rainbows, and we provide a simulation of the rare twinned rainbow, which is believed to be caused by nonspherical water drops.
Interactive sound propagation using compact acoustic transfer operators
Authors: Antani Lakulish , Chandak Anish , Savioja Lauri , Manocha Dinesh
Published: February 2012

We present an interactive sound propagation algorithm that can compute high orders of specular and diffuse reflections as well as edge diffractions in response to moving sound sources and a moving listener. Our formulation is based on a precomputed acoustic transfer operator, which we compactly represent using the Karhunen-Loeve transform. At runtime, we use a two-pass approach that combines acoustic radiance transfer with interactive ray tracing to compute early reflections as well as higher-order reflections and late reverberation. The overall approach allows accuracy to be traded off for improved performance at runtime, and has a low memory overhead. We demonstrate the performance of our algorithm on different scenarios, including an integration of our algorithm with Valve's Source game engine.
Three-dimensional proxies for hand-drawn characters
Authors: Jain Eakta , Sheikh Yaser , Mahler Moshe , Hodgins Jessica
Published: February 2012

Drawing shapes by hand and manipulating computer-generated objects are the two dominant forms of animation. Though each medium has its own advantages, the techniques developed for one medium are not easily leveraged in the other medium because hand animation is two-dimensional, and inferring the third dimension is mathematically ambiguous. A second challenge is that the character is a consistent three-dimensional (3D) object in computer animation while hand animators introduce geometric inconsistencies in the two-dimensional (2D) shapes to better convey a character's emotional state and personality. In this work, we identify 3D proxies to connect hand-drawn animation and 3D computer animation. We present an integrated approach to generate three levels of 3D proxies: single-points, polygonal shapes, and a full joint hierarchy. We demonstrate how this approach enables one medium to take advantage of techniques developed for the other; for example, 3D physical simulation is used to create clothes for a hand-animated character, and a traditionally trained animator is able to influence the performance of a 3D character while drawing with paper and pencil.
BRDF models for accurate and efficient rendering of glossy surfaces
Authors: Löw Joakim , Kronander Joel , Ynnerman Anders , Unger Jonas
Published: February 2012

This article presents two new parametric models of the
Bidirectional Reflectance Distribution Function
(BRDF), one inspired by the Rayleigh-Rice theory for light scattering from optically smooth surfaces, and one inspired by micro-facet theory. The models represent scattering from a wide range of glossy surface types with high accuracy. In particular, they enable representation of types of surface scattering which previous parametric models have had trouble modeling accurately. In a study of the scattering behavior of measured reflectance data, we investigate what key properties are needed for a model to accurately represent scattering from glossy surfaces. We investigate different parametrizations and how well they match the behavior of measured BRDFs. We also examine the scattering curves which are represented in parametric models by different distribution functions. Based on the insights gained from the study, the new models are designed to provide accurate fittings to the measured data. Importance sampling schemes are developed for the new models, enabling direct use in existing production pipelines. In the resulting renderings we show that the visual quality achieved by the models matches that of the measured data.
Fluid simulation using Laplacian eigenfunctions
Authors: De Witt Tyler , Lessig Christian , Fiume Eugene
Published: February 2012

We present an algorithm for the simulation of incompressible fluid phenomena that is computationally efficient and leads to visually convincing simulations with far fewer degrees of freedom than existing approaches. Rather than using an Eulerian grid or Lagrangian elements, we represent vorticity and velocity using a basis of global functions defined over the entire simulation domain. We show that choosing Laplacian eigenfunctions for this basis provides benefits, including correspondence with spatial scales of vorticity and precise energy control at each scale. We perform Galerkin projection of the Navier-Stokes equations to derive a time evolution equation in the space of basis coefficients. Our method admits closed-form solutions on simple domains but can also be implemented efficiently on arbitrary meshes.
Specular reflection from woven cloth
Authors: Irawan Piti , Marschner Steve
Published: February 2012

The appearance of a particular fabric is produced by variations in both large-scale reflectance and small-scale texture as the viewing and illumination angles change across the surface. This article presents a study of the reflectance and texture of woven cloth that aims to identify and model important optical features of cloth appearance. New measurements are reported for a range of fabrics including natural and synthetic fibers as well as staple and filament yarns. A new scattering model for woven cloth is introduced that describes the reflectance and the texture based on an analysis of specular reflection from the fibers. Unlike data-based models, our procedural model doesn't require image data. It can handle a wide range of fabrics using a small set of physically meaningful parameters that describe the characteristics of the fibers, the geometry of the yarns, and the pattern of the weave. The model is validated against the measurements and evaluated by comparisons to high-resolution video of the real fabrics and to BTF models of two of the fabrics.
An adaptive write buffer management scheme for flash-based SSDs
Authors: Wu Guanying , He Xubin , Eckart Ben
Published: February 2012

Solid State Drives (SSD's) have shown promise to be a candidate to replace traditional hard disk drives. The benefits of SSD's over HDD's include better durability, higher performance, and lower power consumption, but due to certain physical characteristics of NAND flash, which comprise SSD's, there are some challenging areas of improvement and further research. We focus on the layout and management of the small amount of RAM that serves as a cache between the SSD and the system that uses it. Of the techniques that have previously been proposed to manage this cache, we identify several sources of inefficient cache space management due to the way pages are clustered in blocks and the limited replacement policy. We find that in many traces hot pages reside in otherwise cold blocks, and that the spatial locality of most clusters can be fully exploited in a limited time period, so we develop a hybrid page/block architecture along with an advanced replacement policy, called BPAC, or Block-Page Adaptive Cache, to exploit both temporal and spatial locality. Our technique involves adaptively partitioning the SSD on-disk cache to separately hold pages with high temporal locality in a page list and clusters of pages with low temporal but high spatial locality in a block list. In addition, we have developed a novel mechanism for flash-based SSD's to characterize the spatial locality of the disk I/O workload and an approach to dynamically identify the set of low spatial locality clusters. We run trace-driven simulations to verify our design and find that it outperforms other popular flash-aware cache schemes under different workloads. For instance, compared to a popular flash aware cache algorithm BPLRU, BPAC reduces the number of cache evictions by up to 79.6% and 34% on average.
A caching-oriented management design for the performance enhancement of solid-state drives
Authors: Chang Yuan-Hao , Hsieh Cheng-Kang , Huang Po-Chun , Hsiu Pi-Cheng
Published: February 2012

While solid-state drives are excellent alternatives to hard disks in mobile devices, a number of performance and reliability issues need to be addressed. In this work, we design an efficient flash management scheme for the performance improvement of low-cost MLC flash memory devices. Specifically, we design an efficient flash management scheme for multi-chipped flash memory devices with cache support, and develop a two-level address translation mechanism with an adaptive caching policy. We evaluated the approach on real workloads. The results demonstrate that it can improve the performance of multi-chipped solid-state drives through logical-to-physical mappings and concurrent accesses to flash chips.
Uncertainty-based active learning with instability estimation for text classification
Authors: Zhu Jingbo , Ma Matthew
Published: February 2012

This article deals with pool-based active learning with uncertainty sampling. While existing uncertainty sampling methods emphasize selection of instances near the decision boundary to increase the likelihood of selecting informative examples, our position is that this heuristic is a surrogate for selecting examples for which the current learning algorithm iteration is likely to misclassify. To more directly model this intuition, this article augments such uncertainty sampling methods and proposes a simple
instability
-based selective sampling approach to improving uncertainty-based active learning, in which the instability degree of each unlabeled example is estimated during the learning process. Experiments on seven evaluation datasets show that instability-based sampling methods can achieve significant improvements over the traditional uncertainty sampling method. In terms of the average percentage of actively selected examples required for the learner to achieve 99% of its performance when training on the entire dataset, instability sampling and sampling by instability and density methods achieve better effectiveness in annotation cost reduction than random sampling and traditional entropy-based uncertainty sampling. Our experimental results have also shown that instability-based methods yield no significant improvement for active learning with SVMs when a popular sigmoidal function is used to transform SVM outputs to posterior probabilities.
Knowledgeable beginners
Authors: Meyer Bertrand
Published: February 2012

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

twitter

Follow us on Twitter at http://twitter.com/blogCACM

http://cacm.acm.org/blogs/blog-cacm

Bertrand Meyer presents data on the computer and programming knowledge of two groups of novice CS students.
SAGE
Authors: Godefroid Patrice , Levin Michael Y. , Molnar David
Published: February 2012

SAGE has had a remarkable impact at Microsoft.
The next generation of GPS navigation systems
Authors: Huang J. Y. , Tsai C. H. , Huang S. T.
Published: February 2012

A live-view GPS navigation system ensures that a user's cognitive map is consistent with the navigation map.
The grand challenge of computer Go
Authors: Gelly Sylvain , Kocsis Levente , Schoenauer Marc , Sebag Michèle , Silver David , Szepesvári Csaba , Teytaud Olivier
Published: February 2012

The ancient oriental game of Go has long been considered a grand challenge for artificial intelligence. For decades, computer Go has defied the classical methods in game tree search that worked so successfully for chess and checkers. However, recent play in computer Go has been transformed by a new paradigm for tree search based on Monte-Carlo methods. Programs based on Monte-Carlo tree search now play at human-master levels and are beginning to challenge top professional players. In this paper, we describe the leading algorithms for Monte-Carlo tree search and explain how they have advanced the state of the art in computer Go.
Optimizing quality of service in real-time systems under energy constraints
Authors: Nassiffe Ríad , Camponogara Eduardo , Lima George
Published: February 2012

Embedded real-time systems powered by batteries require suitable support for energy-savings at the operating system level. Mechanisms to do so must take into consideration not only energy constraints but also schedulability since, in this kind of system, tasks must execute within predefined time windows. On top of that, it is desired that application quality of service (QoS) is optimized.

In this paper we present a framework capable of maximizing application QoS subject to both schedulability and energy constraints. It is assumed that application tasks may have multiple operating modes, each of which exhibiting a specific QoS level when running at a specific processor operating frequency. Although the formulated problem is NP-Hard, experimental analysis has shown that the derived heuristic to solve it achieves very good approximation results and presents low running time.
Report on the third workshop on hot topics in software upgrades (HotSWUp'11)
Authors: Hayden Christopher M. , Neamtiu Iulian
Published: February 2012

Report on the third workshop on hot topics in software upgrades (HotSWUp'11).

The workshop combined presentations of peer-reviewed research papers with a keynote speech on the practical issues related to performing large-scale upgrades. The audience included researchers and practitioners from academia, industry, and government. In addition to the technical presentations, the program allowed ample time for discussions, which were driven by debate questions provided in advance by the presenters.

HotSWUp provides a premier forum for discussing problems that are often considered niche topics in the established research communities. For example, the technical discussions at HotSWUp'11 covered dynamic software updates, package management tools, database schema upgrades, upgrades of systems with real-time constraints, upgrading satellite software, and highlighted many synergies among these and other topics.
Leucine and mTORC1: a complex relationship
Authors: Dodd Kayleigh M. , Tee Andrew R.
Published: February 2012

Amino acid availability is a rate-limiting factor in the regulation of protein synthesis. When amino acid supplies become restricted, mammalian cells employ homeostatic mechanisms to rapidly inhibit processes such as protein synthesis, which demands high levels of amino acids. Muscle cells in particular are subject to high protein turnover rates to maintain amino acid homeostasis. Mammalian target of rapamycin complex 1 (mTORC1) is an evolutionary conserved multiprotein complex that coordinates a network of signaling cascades and functions as a key mediator of protein translation, gene transcription, and autophagy. Signal transduction through mTORC1, which is centrally involved in muscle growth through enhanced protein translation, is governed by intracellular amino acid supply. The branched-chain amino acid leucine is critical for muscle growth and acts in part through activation of mTORC1. Recent research has revealed that mTORC1 signaling is coordinated primarily at the lysosomal membranes. This discovery has sparked a wealth of research in this field, revealing several different signaling molecules involved in transducing the amino acid signal to mTORC1, including the Rag GTPases, MAP4K3, and Vps34/ULK1. This review evaluates the current knowledge regarding cellular mechanisms that control and sense the intracellular amino acid pool. We discuss the role of leucine and mTORC1 in the regulation of amino acid transport via the system L and system A transporters such as LAT1 and SNAT2, as well as protein degradation via autophagic and proteasomal pathways. We also describe the complexities of energy homeostasis via AMPK and cell receptor-mediated growth signals that also converge on mTORC1. Leucine is a particularly potent regulator of protein turnover, to the extent where leucine stimulation alone is sufficient to stimulate mTORC1 signal transduction. The significance of leucine in this context is not yet known; however, recent advancements in this area will also be covered within this review.
Investigation of Association between Susceptibility to Leprosy and SNPs inside and near theBCHEGene of Butyrylcholinesterase
Authors: Gomes Henrique J. P. , Souza Ricardo L. R. , Prevedello Flávia Costa , Mira Marcelo Távora , Chautard-Freire-Maia Eleidi A.
Published: February 2012

Leprosy is a chronic disease caused byMycobacterium lepraeand affects the skin and the peripheral nervous system. Butyrylcholinesterase is coded by theBCHEgene, and the atypical allele (70G; rs1799807) has been investigated as a leprosy risk factor, with conflicting results. The present study estimated the frequencies of variants of rs1799807 and of five additional SNPs at theBCHEgene or near it: rs1126680, rs1803274, rs2863381, rs4440084, and rs4387996. A total of 167 patients and 150 healthy controls were genotyped by TaqMan PCR. Significantly higher allelic (70G) and genotypic (70DG) frequencies in rs1799807 were found in the patient group, with odds ratio (OR) of 6.33 (1.40 to 28.53) for the heterozygote. This finding was replicated in a comparison of the cases against a control group of 361 blood donors. The present data suggest that the atypical BChE variant may predispose to leprosyper se.
An Efficient Renewable Energy Management and Sharing System for Sustainable Embedded Devices
Authors: Zhu Ting , Zhou Chang
Published: February 2012

We present the design and evaluation of a capacitor‐driven efficient renewable energy management and sharing system, called REMS system, that is designed to replace battery‐based energy storage units. We first identify potential applications and requirements of the REMS system.
Then we describe the design of REMS system which aims
at minimizing the energy leaked away and providing accurate
and fine‐grained energy sharing between embedded devices.
We extensively evaluate our system under different real‐world
settings. Results indicate that our charging and discharging control
can effectively minimize the energy leaked away. Moreover, the
energy sharing design can efficiently share renewable energy
among multiple devices and significantly extend the lifetime of a
system.
Transvaginal Sonographic Evaluation of the Cervix in Asymptomatic Singleton Pregnancy and Management Options in Short Cervix
Authors: Arisoy Resul , Yayla Murat
Published: February 2012

Preterm delivery (PTD), defined as birth before 37 completed weeks of gestation, is the leading cause of perinatal morbidity and mortality. Evaluation of the cervical morphology and biometry with transvaginal ultrasonography at 16–24 weeks of gestation is a useful tool to predict the risk of preterm birth in low- and high-risk singleton pregnancies. For instance, a sonographic cervical length (CL) > 30 mm and present cervical gland area have a 96-97% negative predictive value for preterm delivery at <37 weeks. Available evidence supports the use of progesterone to women with cervical length ≤25 mm, irrespective of other risk factors. In women with prior spontaneous PTD with asymptomatic cervical shortening (CL ≤ 25 mm), prophylactic cerclage procedure must be performed and weekly to every two weeks follow-up is essential. This article reviews the evidence in support of the clinical introduction of transvaginal sonography for both the prediction and management of spontaneous preterm labour.
Potential of Novel EPO Derivatives in Limb Ischemia
Authors: Joshi Dhiraj , Tsui Janice , Yu Rebekah , Shiwen Xu , Selvakumar Sadasivam , Abraham David J. , Baker Daryll M.
Published: February 2012

Erythropoietin (EPO) has tissue-protective properties, but it increases the risk of thromboembolism by raising the haemoglobin concentration. New generation of EPO derivatives is tissue protective without the haematopoietic side effects. Preclinical studies have demonstrated their effectiveness and safety. This paper summarizes the development in EPO derivatives with emphasis on their potential use in critical limb ischaemia.
Markers of Inflammation and Fibrosis in Alcoholic Hepatitis and Viral Hepatitis C
Authors: Neuman Manuela G. , Schmilovitz-Weiss Hemda , Hilzenrat Nir , Bourliere Marc , Marcellin Patrick , Trepo Cristhian , Mazulli Tony , Moussa George , Patel Ankit , Baig Asad A. , Cohen Lawrence
Published: February 2012

High levels of profibrinogenic cytokine transforming factor beta (TGF-β), metalloprotease (MMP2), and tissue inhibitor of matrix metalloprotease 1 (TIMP1) contribute to fibrogenesis in hepatitis C virus (HCV) infection and in alcohol-induced liver disease (ALD). The aim of our study was to correlate noninvasive serum markers in ALD and HCV patients with various degrees of inflammation and fibrosis in their biopsies.Methods. Serum cytokines levels in HCV-infected individuals in the presence or absence of ALD were measured. Student's-t-test with Bonferroni correction determined the significance between the groups.Results. Both tumor-necrosis-factor- (TNF)-αand TGF-βlevels increased significantly with the severity of inflammation and fibrosis. TGF-βlevels increased significantly in ALD patients versus the HCV patients. Proinflammatory cytokines’ responses to viral and/or toxic injury differed with the severity of liver inflammation. A combination of these markers was useful in predicting and diagnosing the stages of inflammation and fibrosis in HCV and ALD.Conclusion. Therapeutic monitoring of TGF-βand metalloproteases provides important insights into fibrosis.
Isolation Enhancement between Indoor Repeater Antennas with Chip Resistor Embedded FSS
Authors: Lee Jae-Yeong , Kim Byeongkwan , Park Myun-Joo , Lee Byungje
Published: February 2012

The isolation enhancement between the donor antenna and the service antenna for indoor repeater systems is presented by using a frequency-selective surface (FSS). A unit cell of the proposed FSS consists of a quarter-wavelength resonator, a chip resistor, an FR4 substrate, and a ground plane. Applying the unit cells of the proposed FSS embedded a chip resistor on the side walls of each reflector for indoor WCDMA repeater antennas and aligning them along with the cross-polarization of each antenna, the isolation is improved by about 13 dB at the WCDMA band.
The Impact of an Intervention Taught by Trained Teachers on Childhood Fruit and Vegetable Intake: A Randomized Trial
Authors: Rosário Rafaela , Araújo Ana , Oliveira Bruno , Padrão Patrícia , Lopes Oscar , Teixeira Vítor , Moreira André , Barros Renata , Pereira Beatriz , Moreira Pedro
Published: February 2012

Our study aimed to assess the impact of a six-months nutrition program, taught by trained teachers, on fruit and vegetable consumption among children in grades 1 to 4. Four hundred and sixty-four children (239 female), 6 to 12 years old, from seven elementary schools were assigned to this randomized trial. Teachers were trained by researchers over six months, according to the following topics: nutrition, healthy eating, and strategies to increase physical activity. After each session, teachers were encouraged to develop activities in the classroom on the topics learned. Children's sociodemographic, anthropometric, dietary, and physical activity data were assessed at baseline and at the end of the intervention. The effect sizes ranged between small (Cohen'sd=0.12on “other vegetables”) to medium (0.56 on “fruit and vegetable”), and intervened children reported a significantly higher consumption of vegetables and fruit. Interventions involving trained teachers offer promise to increase consumption of fruit and vegetable in children.
Loss to Followup in HIV-Infected Patients from Asia-Pacific Region: Results from TAHOD
Authors: Zhou Jialun , Tanuma Junko , Chaiwarith Romanee , Lee Christopher K. C. , Law Matthew G. , Kumarasamy Nagalingeswaran , Phanuphak Praphan , Chen Yi-Ming A. , Kiertiburanakul Sasisopin , Zhang Fujie , Vonthanak Saphonn , Ditangco Rossana , Pujari Sanjay , Choi Jun Yong , Parwati Merati Tuti , Yunihastuti Evy , Li Patrick C. K. , Kamarulzaman Adeeba , Nguyen Van Kinh , Thuy Pham Thi Thanh , Lim Poh Lian
Published: February 2012

This study examined characteristics of HIV-infected patients in the TREAT Asia HIV Observational Database who were lost to follow-up (LTFU) from treatment and care. Time from last clinic visit to 31 March 2009 was analysed to determine the interval that best classified LTFU. Patients defined as LTFU were then categorised into permanently LTFU (never returned) and temporary LTFU (re-entered later), and these groups compared. A total of 3626 patients were included (71% male). No clinic visits for 180 days was the best-performing LTFU definition (sensitivity 90.6%, specificity 92.3%). During 7697 person-years of follow-up, 1648 episodes of LFTU were recorded (21.4 per 100-person-years). Patients LFTU were younger (P=0.002), had HIV viral load ≥500 copies/mL or missing (P=0.021), had shorter history of HIV infection (P=0.048), and received no, single- or double-antiretroviral therapy, or a triple-drug regimen containing a protease inhibitor (P<0.001). 48% of patients LTFU never returned. These patients were more likely to have low or missing haemoglobin (P<0.001), missing recent HIV viral load (P<0.001), negative hepatitis C test (P=0.025), and previous temporary LTFU episodes (P<0.001). Our analyses suggest that patients not seen at a clinic for 180 days are at high risk of permanent LTFU, and should be aggressively traced.
Biomarkers of Subclinical Atherosclerosis in Patients with Autoimmune Disorders
Authors: Profumo Elisabetta , Di Franco Manuela , Buttari Brigitta , Masella Roberta , Filesi Carmelina , Tosti Maria Elena , Scrivo Rossana , Scarno Antongiulio , Spadaro Antonio , Saso Luciano , Riganò Rachele
Published: February 2012

Atherosclerosis is accelerated in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We investigated a possible association of oxidized low-density lipoproteins (ox-LDLs), nitric oxide (NO), 3-nitrotyrosine, vitamin A, vitamin E, andβ-carotene serum levels with subclinical atherosclerosis in RA and PsA. By the use of ELISA, we observed higher ox-LDL levels in patients with intima-media thickness (IMT) > 1 than in patients with IMT ≤ 1 and a negative correlation between NO levels and IMT values. By the use of high-performance liquid chromatography, we determined higher levels of vitamin A in patients with PsA and IMT ≤ 1 than in controls and lower levels ofβ-carotene in patients with RA and PsA than in controls.β-carotene concentrations were negatively correlated to the duration of disease in RA. Our study confirms that ox-LDLs and NO may be markers of accelerated atherosclerosis in RA and PsA whereas vitamins seem to be associated only to the presence of the autoimmune disorders.
Effects of IRF5 Lupus Risk Haplotype on Pathways Predicted to Influence B Cell Functions
Authors: Guthridge Joel M. , Clark Daniel N. , Templeton Amanda , Dominguez Nicolas , Lu Rufei , Vidal Gabriel S. , Kelly Jennifer A. , Kauffman Kenneth M. , Harley John B. , Gaffney Patrick M. , James Judith A. , Poole Brian D.
Published: February 2012

Both genetic and environmental interactions affect systemic lupus erythematosus (SLE) development and pathogenesis. One known genetic factor associated with lupus is a haplotype of the interferon regulatory factor 5 (IRF5) gene. Analysis of global gene expression microarray data using gene set enrichment analysis identified multiple interferon- and inflammation-related gene sets significantly overrepresented in cells with the risk haplotype. Pathway analysis using expressed genes from the significant gene sets impacted by theIRF5risk haplotype confirmed significant correlation with the interferon pathway, Toll-like receptor pathway, and the B-cell receptor pathway. SLE patients with theIRF5risk haplotype have a heightened interferon signature, even in an unstimulated state (P=0.011), while patients with theIRF5protective haplotype have a B cell interferon signature similar to that of controls. These results identify multiple genes in functionally significant pathways which are affected by IRF5 genotype. They also establish the IRF5 risk haplotype as a key determinant of not only the interferon response, but also other B-cell pathways involved in SLE.
Perisynaptic GABA Receptors: The Overzealous Protector
Authors: Clarkson Andrew N.
Published: February 2012

An attempt to find pharmacological therapies to treat stroke patients and minimize the extent of cell death has seen the failure of dozens of clinical trials. As a result, stroke/cerebral ischemia is the leading cause of lasting adult disability. Stroke-induced cell death occurs due to an excess release of glutamate. As a consequence to this, a compensatory increased release of GABA occurs that results in the subsequent internalization of synaptic GABAAreceptors and spillover onto perisynaptic GABAAreceptors, resulting in increased tonic inhibition. Recent studies show that the brain can engage in a limited process of neural repair after stroke. Changes in cortical sensory and motor maps and alterations in axonal structure are dependent on patterned neuronal activity. It has been assumed that changes in neuronal excitability underlie processes of neural repair and remapping of cortical sensory and motor representations. Indeed, recent evidence suggests that local inhibitory and excitatory currents are altered after stroke and modulation of these networks to enhance excitability during the repair phase can facilitate functional recovery after stroke. More specifically, dampening tonic GABA inhibition can afford an early and robust improvement in functional recovery after stroke.
Acupuncture Use among American Adults: What Acupuncture Practitioners Can Learn from National Health Interview Survey 2007?
Authors: Zhang Yan , Lao Lixing , Chen Haiyan , Ceballos Rodrigo
Published: February 2012

This paper examined the National Health Interview Survey (NHIS) 2007 and explored acupuncture users sociodemographics characteristics, reasons and the nature of acupuncture use, and the relationship of such use with conventional medical care. All individuals who completed adults core interviews (N= 23,393) were included. Three subsets of samples (nonuser, former user, and recent user) were used in the analysis performed in Stata. Our findings revealed that ever acupuncture user (including former and recent user) increased from 4.2% to 6.3% of the population, representing 8.19 million and 14.01 million users in 2002 and 2007, respectively. We expected this trend to continue. People not only used acupuncture as a complementary and alternative approach to conventional treatment for a specific health condition, but also used it as a preventive means to promote general health. Effectiveness and safety appeared not to be the main predictors of acupuncture use; rather, awareness, cost, and insurance coverage played a bigger role in decision making.
Acupuncture for the Treatment of Opiate Addiction
Authors: Lin Jaung-Geng , Chan Yuan-Yu , Chen Yi-Hung
Published: February 2012

Acupuncture is an accepted treatment worldwide for various clinical conditions, and the effects of acupuncture on opiate addiction have been investigated in many clinical trials. The present review systematically analyzed data from randomized clinical trials published in Chinese and English since 1970. We found that the majority agreed on the efficacy of acupuncture as a strategy for the treatment of opiate addiction. However, some of the methods in several included trials have been criticized for their poor quality. This review summarizes the quality of the study design, the types of acupuncture applied, the commonly selected acupoints or sites of the body, the effectiveness of the treatment, and the possible mechanism underlying the effectiveness of acupuncture in these trials.
The Diabetic Heart: Too Sweet for Its Own Good?
Authors: Whittington Hannah J. , Babu Girish G. , Mocanu Mihaela M. , Yellon Derek M. , Hausenloy Derek J.
Published: February 2012

Diabetes mellitus is a major risk factor for ischemic heart disease (IHD). Patients with diabetes and IHD experience worse clinical outcomes, suggesting that the diabetic heart may be more susceptible to ischemia-reperfusion injury (IRI). In contrast, the animal data suggests that the diabetic heart may be either more, equally, or even less susceptible to IRI. The conflicting animal data may be due to the choice of diabetic and/or IRI animal model. Ischemic conditioning, a phenomenon in which the heart is protected against IRI by one or more brief nonlethal periods of ischemia and reperfusion, may provide a novel cardioprotective strategy for the diabetic heart. Whether the diabetic heart is amenable to ischemic conditioning remains to be determined using relevant animal models of IRI and/or diabetes. In this paper, we review the limitations of the current experimental models used to investigate IRI and cardioprotection in the diabetic heart.
Multiple Positive Solutions for Nonlinear Semipositone Fractional Differential Equations
Authors: Zhou Wen-Xue , Peng Ji-Gen , Chu Yan-Dong
Published: February 2012

We present some new multiplicity of positive solutions results for nonlinear semipositone fractional boundary value problem , where 2 < α ≤ 3 is a real number and is the standard Riemann‐Liouville differentiation. One example is also given to illustrate the main result.
Annexin A2 at the Interface of Actin and Membrane Dynamics: A Focus on Its Roles in Endocytosis and Cell Polarization
Authors: Grieve Adam G. , Moss Stephen E. , Hayes Matthew J.
Published: February 2012

Annexins are a family of calcium- and phospholipid-binding proteins found in nearly all eukaryotes. They are structurally highly conserved and have been implicated in a wide range of cellular activities. In this paper, we focus on Annexin A2 (AnxA2). Altered expression of this protein has been identified in a wide variety of cancers, has also been found on the HIV particle, and has been implicated in the maturation of the virus. Recently, it has also been shown to have an important role in the establishment of normal apical polarity in epithelial cells. We synthesize here the known biochemical properties of this protein and the extensive literature concerning its involvement in the endocytic pathway. We stress the importance of AnxA2 as a platform for actin remodeling in the vicinity of dynamic cellular membranes, in the hope that this may shed light on the normal functions of the protein and its contribution to disease.
Personal Identification Based on Vectorcardiogram Derived from Limb Leads Electrocardiogram
Authors: Lee Jongshill , Chee Youngjoon , Kim Inyoung
Published: February 2012

We propose a new method for personal identification using the derived vectorcardiogram (dVCG), which is derived from the limb leads electrocardiogram (ECG). The dVCG was calculated from the standard limb leads ECG using the precalculated inverse transform matrix. Twenty‐one features were extracted from the dVCG, and some or all of these 21 features were used in support vector machine (SVM) learning and in tests. The classification accuracy was 99.53%, which is similar to the previous dVCG analysis using the standard 12‐lead ECG. Our experimental results show that it is possible to identify a person by features extracted from a dVCG derived from limb leads only. Hence, only three electrodes have to be attached to the person to be identified, which can reduce the effort required to connect electrodes and calculate the dVCG.
Ultrasound of the Small Bowel in Crohn’s Disease
Authors: Calabrese Emma , Zorzi Francesca , Pallone Francesco
Published: February 2012

Several radiological and endoscopic techniques are now available for the study of inflammatory bowel diseases. In everyday practice, the choice of the technique to be used depends upon its availability and a careful evaluation of diagnostic accuracy, clinical usefulness, safety, and cost. The recent development of innovative and noninvasive imaging techniques has led to a new and exciting area in the exploration of the gastrointestinal tract, especially in Crohn’s disease patients by using ultrasound with oral or intravenous contrast.
The Impact of Severe Obesity on Post-Acute Rehabilitation Efficiency, Length of Stay, and Hospital Costs
Authors: Padwal Raj S. , Wang Xiaoming , Sharma Arya M. , Dyer David
Published: February 2012

Background and Objective. The purpose of this retrospective observational study was to examine the influence of severe obesity on length of stay (LOS), rehabilitation efficiency, and hospital costs post-acute rehabilitation in a population-based, tertiary care, publicly-funded regional rehabilitation center.Participants. 42 severely obese subjects (mean age 53 y; mean BMI 50.9 kg/m2) and 42 nonobese controls (mean age 59 y; mean BMI 23.0 kg/m2) matched by sex and admitting diagnosis.Main Outcome Measures. Total LOS, rehab LOS, waiting for transfer LOS, Fuctional Independence Measure (FIM) efficiency, and hospital costs.Results. Compared to controls, severely obese subjects experienced longer total LOS (98.4 vs. 37.4 days;P=0.03), rehabilitation LOS (55.8 vs. 37.4 days;P=0.04), and waiting for transfer LOS (42.6 vs. 0 days;P=0.006); increased hospital costs ($115,822 vs. $43,969;P=0.03); and similar FIM efficiency (0.58 vs. 0.67;P=0.27). Severe obesity was an independent predictor of total LOS (beta-coefficient 0.51;P=0.03), rehab LOS (0.46;P=0.02) but not FIM efficiency (−0.63;P=0.06).Conclusion. Severe obesity adversely affects rehabilitation LOS and expenditures. Targeted interventions in severely obese individuals to optimize post-acute rehabilitation care delivery are needed.
Fine Structure of Glycosaminoglycans from Fresh and Decellularized Porcine Cardiac Valves and Pericardium
Authors: Cigliano Antonio , Gandaglia Alessandro , Lepedda Antonio Junior , Zinellu Elisabetta , Naso Filippo , Gastaldello Alessandra , Aguiari Paola , De Muro Pierina , Gerosa Gino , Spina Michele , Formato Marilena
Published: February 2012

Cardiac valves are dynamic structures, exhibiting a highly specialized architecture consisting of cells and extracellular matrix with a relevant proteoglycan and glycosaminoglycan content, collagen and elastic fibers. Biological valve substitutes are obtained from xenogenic cardiac and pericardial tissues. To overcome the limits of such non viable substitutes, tissue engineering approaches emerged to create cell repopulated decellularized scaffolds. This study was performed to determine the glycosaminoglycans content, distribution, and disaccharides composition in porcine aortic and pulmonary valves and in pericardium before and after a detergent-based decellularization procedure. The fine structural characteristics of galactosaminoglycans chondroitin sulfate and dermatan sulfate were examined by FACE. Furthermore, the mechanical properties of decellularized pericardium and its propensity to be repopulated by in vitro seeded fibroblasts were investigated. Results show that galactosaminoglycans and hyaluronan are differently distributed between pericardium and valves and within heart valves themselves before and after decellularization. The distribution of glycosaminoglycans is also dependent from the vascular district and topographic localization. The decellularization protocol adopted resulted in a relevant but not selective depletion of galactosaminoglycans. As a whole, data suggest that both decellularized porcine heart valves and bovine pericardium represent promising materials bearing the potential for future development of tissue engineered heart valve scaffolds.
BRAF(V600) Inhibitor GSK2118436 Targeted Inhibition of Mutant BRAF in Cancer Patients Does Not Impair Overall Immune Competency
Authors: Hong David S. , Vence Luis , Falchook Gerald , Radvanyi Laszlo G. , Liu Chengwen , Goodman Vicki , Legos Jeffery J. , Blackman Sam , Scarmadio Antonio , Kurzrock Razelle , Lizee Gregory , Hwu Patrick
Published: February 2012

Purpose: An intact immune system likely contributes to the outcome of treatment and may be important for clearance of drug-resistant tumor cells and for prevention of recurrence. Although pharmacologic inhibition of BRAF(V600E) in melanoma patients, which is linked to immune suppression, results in an initial response rate, these responses are typically of limited duration. Combining immunotherapeutic drugs with kinase-targeted agents is an attractive strategy to increase clinical efficacy. Evidence suggesting that mitogen-activated protein kinase pathway activation in tumor cells contributes to immune suppression suggests that the two approaches may be synergistic, provided that BRAF(V600E) inhibitors are nontoxic to immune cells.

Methods: To assess effects of mutant BRAF inhibition on systemic immunity, we studied 13 patients with tumors carrying a BRAF mutation who underwent treatment with GSK2118436, a V600 mutant BRAF-specific inhibitor. We carried out peripheral blood immunomonitoring before and following one or two 28-day cycles of treatment.

Results: GSK2118436 treatment had no detectable impact on most immune parameters tested, including serum cytokine levels, peripheral blood cell counts, leukocyte subset frequencies, and memory CD4+ and CD8+ T-cell recall responses. A slight increase in serum TNF-α over the course of treatment was observed. In addition, three of the four human leukocyte antigen-A2–positive patients experienced a modest increase in circulating tumor antigen–specific CD8+ T cells following BRAF(V600) inhibitor therapy.

Conclusions: GSK2118436 treatment results in no detectable negative impact on existing systemic immunity or the de novo generation of tumor-specific T cells. These findings suggest that future trials combining specific BRAF(V600E) inhibition with immunotherapy should not impair immune response. Clin Cancer Res; 18(8); 2326–35. ©2012 AACR.
Protein Expression of Estrogen Receptors α and β and Aromatase in Myometrium and Uterine Leiomyoma
Authors: Olmos Grings Anelise , Lora Vanessa , Dias Ferreira Gustavo , Simoni Brum Ilma , von Eye Corleta Helena , Capp Edison
Published: February 2012

Background: Leiomyomas are the most common tumors of the female reproductive tract and a major public health problem. The mechanism of tumorigenesis is unknown, but evidence suggests that estrogens regulate cell proliferation and myoma growth. This effect might be due to different amounts of estrogen receptors (ERα and ERβ) in normal and myoma tissues and overexpression of aromatase P450 in myomas. Purpose: To assess protein expression of ERs and aromatase in leiomyomas and normal adjacent myometrium of premenopausal women. Methods: Samples were collected from 12 premenopausal women admitted for abdominal hysterectomy due to fibroids. Results: The protein expression of ERα, ERβ and aromatase was similar in leiomyoma and normal myometrium (p = 0.239, p = 0.695 and p = 0.203, respectively). Conclusions: In this analysis of 12 matched leiomyoma and myometrial samples, the data do not support the theory that overexpression ERα, ERβ and aromatase in uterine leiomyomas compared to adjacent myometrium are the cause of tumor growth. The estrogens may exert their growth-stimulatory effects on leiomyomas intermediated by other elements, such as cytokines and growth or apoptosis factors. The effect of estrogen on the growth and development of fibroids is complex and far from being completely understood.
Post-Weaning to Pre-Pubertal (‘Juvenile’) Stress: A Model of Induced Predisposition to Stress-Related Disorders
Authors: Horovitz O. , Tsoory M.M. , Hall J. , Jacobson-Pick S. , Richter-Levin G.
Published: February 2012

Human studies suggest that childhood trauma predisposes individuals to develop stress-related disorders such as depression and post-traumatic stress disorder (PTSD). Recent years have witnessed growing interest in effectively modeling in animals the long-term effects of childhood emotional trauma on stress responses in adulthood. Most studies concerned with the impact of early-life stress on subsequent stress responses in adulthood in rodents have focused on the post-natal pre-weaning period. However, psychiatric studies often refer to human childhood rather than infancy when investigating the patients’ traumatic history of stress-related psychopathologies. In accordance with that, we have examined the consequences of stress exposure at a later early-life period, the post-weaning, pre-puberty (juvenile) period, which holds greater resemblance to human childhood. This review summarizes a series of studies examining the impact of exposure of rats to stressors during ‘juvenility’ (‘juvenile stress’) on the ability of these animals to cope with stress later in life. Exposure to relatively brief but significant stress experience during juvenility was found to impair the ability of animals to cope with stressful challenges in adulthood. These behavioral manifestations were associated with lasting alterations in limbic system brain regions of neuromodulatory pathways, such as alterations in the expression of cell adhesion molecules, GABAergic system functioning and alterations in levels of circulating corticosterone. Importantly, these studies have also demonstrated considerable individual and sex differences, which call for the development of adequate analysis approaches. The juvenile stress model combined with characterization of individual profiles is presented as a useful model to study in rodents different facets of stress-related disorders and neural mechanisms of vulnerability and resilience to stress.