bluuebunny/crossref_metadata_2025 huggingface dataset:
Metric-aware processing of spherical imagery
Authors: Kazhdan Michael , Hoppe Hugues
Published: December 2010

Processing spherical images is challenging. Because no spherical parameterization is globally uniform, an accurate solver must account for the spatially varying metric. We present the first efficient metric-aware solver for Laplacian processing of spherical data. Our approach builds on the commonly used equirectangular parameterization, which provides differentiability, axial symmetry, and grid sampling. Crucially, axial symmetry lets us discretize the Laplacian operator just once per grid row. One difficulty is that anisotropy near the poles leads to a poorly conditioned system. Our solution is to construct an adapted hierarchy of finite elements, adjusted at the poles to maintain derivative continuity, and selectively coarsened to bound element anisotropy. The resulting elements are nested both within and across resolution levels. A streaming multigrid solver over this hierarchy achieves excellent convergence rate and scales to huge images. We demonstrate applications in reaction-diffusion texture synthesis and panorama stitching and sharpening.
Multi-resolution isotropic strain limiting
Authors: Wang Huamin , O'Brien James , Ramamoorthi Ravi
Published: December 2010

In this paper we describe a fast strain-limiting method that allows stiff, incompliant materials to be simulated efficiently. Unlike prior approaches, which act on springs or individual strain components, this method acts on the strain tensors in a coordinate-invariant fashion allowing isotropic behavior. Our method applies to both two-and three-dimensional strains, and only requires computing the singular value decomposition of the deformation gradient, either a small 2x2 or 3x3 matrix, for each element. We demonstrate its use with triangular and tetrahedral linear-basis elements. For triangulated surfaces in three-dimensional space, we also describe a complementary edge-angle-limiting method to limit out-of-plane bending. All of the limits are enforced through an iterative, non-linear, Gauss-Seidel-like constraint procedure. To accelerate convergence, we propose a novel multi-resolution algorithm that enforces fitted limits at each level of a non-conforming hierarchy. Compared with other constraint-based techniques, our isotropic multi-resolution strain-limiting method is straightforward to implement, efficient to use, and applicable to a wide range of shell and solid materials.
A comparative study of image retargeting
Authors: Rubinstein Michael , Gutierrez Diego , Sorkine Olga , Shamir Ariel
Published: December 2010

The numerous works on media retargeting call for a methodological approach for evaluating retargeting results. We present the first comprehensive perceptual study and analysis of image retargeting. First, we create a benchmark of images and conduct a large scale user study to compare a representative number of state-of-the-art retargeting methods. Second, we present analysis of the users' responses, where we find that humans in general agree on the evaluation of the results and show that some retargeting methods are consistently more favorable than others. Third, we examine whether computational image distance metrics can predict human retargeting perception. We show that current measures used in this context are not necessarily consistent with human rankings, and demonstrate that better results can be achieved using image features that were not previously considered for this task. We also reveal specific qualities in retargeted media that are more important for viewers. The importance of our work lies in promoting better measures to assess and guide retargeting algorithms in the future. The full benchmark we collected, including all images, retargeted results, and the collected user data, are available to the research community for further investigation at
http://people.csail.mit.edu/mrub/retargetme.
Parallel Poisson disk sampling with spectrum analysis on surfaces
Authors: Bowers John , Wang Rui , Wei Li-Yi , Maletz David
Published: December 2010

The ability to place surface samples with Poisson disk distribution can benefit a variety of graphics applications. Such a distribution satisfies the blue noise property, i.e. lack of low frequency noise and structural bias in the Fourier power spectrum. While many techniques are available for sampling the plane, challenges remain for sampling arbitrary surfaces. In this paper, we present new methods for Poisson disk sampling with spectrum analysis on arbitrary manifold surfaces. Our first contribution is a parallel dart throwing algorithm that generates high-quality surface samples at interactive rates. It is flexible and can be extended to adaptive sampling given a user-specified radius field. Our second contribution is a new method for analyzing the spectral quality of surface samples. Using the spectral mesh basis derived from the discrete mesh Laplacian operator, we extend standard concepts in power spectrum analysis such as radial means and anisotropy to arbitrary manifold surfaces. This provides a way to directly evaluate the spectral distribution quality of surface samples without requiring mesh parameterization. Finally, we implement our Poisson disk sampling algorithm on the GPU, and demonstrate practical applications involving interactive sampling and texturing on arbitrary surfaces.
Computational highlight holography
Authors: Regg Christian , Rusinkiewicz Szymon , Matusik Wojciech , Gross Markus
Published: December 2010

Computational highlight holography converts three-dimensional computer models into mechanical "holograms" fabricated on (specular) reflective or refractive materials. The surface consists of small grooves with patches of paraboloids or hyperboloids, each of which produces a highlight when illuminated by a directional light. Each highlight appears in different places for different view directions, with the correct binocular and motion parallax corresponding to a virtual 3D point position. Our computational pipeline begins with a 3D model and desired view position, samples the model to generate points that depict its features accurately, and computes a maximal set of non-overlapping patches to be embedded in the surface. We provide a preview of the hologram for the user, then fabricate the surface using a computer-controlled engraving machine. We show a variety of different fabricated holograms: reflective, transmissive, and holograms with color and proper shading. We also present extensions to stationary and animated 2D stippled images.
Axial-cones
Authors: Taguchi Yuichi , Agrawal Amit , Veeraraghavan Ashok , Ramalingam Srikumar , Raskar Ramesh
Published: December 2010

Catadioptric imaging systems are commonly used for wide-angle imaging, but lead to multi-perspective images which do not allow algorithms designed for perspective cameras to be used. Efficient use of such systems requires accurate geometric ray modeling as well as fast algorithms. We present accurate geometric modeling of the multi-perspective photo captured with a spherical catadioptric imaging system usingaxial-cone cameras:multiple perspective cameras lying on an axis each with a different viewpoint and a different cone of rays. This modeling avoids geometric approximations and allows several algorithms developed for perspective cameras to be applied to multi-perspective catadioptric cameras.

We demonstrate axial-cone modeling in the context of rendering wide-angle light fields, captured using a spherical mirror array. We present several applications such as spherical distortion correction, digital refocusing for artistic depth of field effects in wide-angle scenes, and wide-angle dense depth estimation. Our GPU implementation using axial-cone modeling achieves up to three orders of magnitude speed up over ray tracing for these applications.
Free-flowing granular materials with two-way solid coupling
Authors: Narain Rahul , Golas Abhinav , Lin Ming C.
Published: December 2010

We present a novel continuum-based model that enables efficient simulation of granular materials. Our approach fully solves the internal pressure and frictional stresses in a granular material, thereby allows visually noticeable behaviors of granular materials to be reproduced, including freely dispersing splashes without cohesion, and a global coupling between friction and pressure. The full treatment of internal forces in the material also enables two-way interaction with solid bodies. Our method achieves these results at only a very small fraction of computational costs of the comparable particle-based models for granular flows.
Computer-generated residential building layouts
Authors: Merrell Paul , Schkufza Eric , Koltun Vladlen
Published: December 2010

We present a method for automated generation of building layouts for computer graphics applications. Our approach is motivated by the layout design process developed in architecture. Given a set of high-level requirements, an architectural program is synthesized using a Bayesian network trained on real-world data. The architectural program is realized in a set of floor plans, obtained through stochastic optimization. The floor plans are used to construct a complete three-dimensional building with internal structure. We demonstrate a variety of computer-generated buildings produced by the presented approach.
Data-driven suggestions for creativity support in 3D modeling
Authors: Chaudhuri Siddhartha , Koltun Vladlen
Published: December 2010

We introduce data-driven suggestions for 3D modeling. Data-driven suggestions support open-ended stages in the 3D modeling process, when the appearance of the desired model is ill-defined and the artist can benefit from customized examples that stimulate creativity. Our approach computes and presents components that can be added to the artist's current shape. We describe shape retrieval and shape correspondence techniques that support the generation of data-driven suggestions, and report preliminary experiments with a tool for creative prototyping of 3D models.
Chicken ovalbumin upstream promoter-transcription factor II regulates nuclear receptor, myogenic, and metabolic gene expression in skeletal muscle cells
Authors: Crowther Lisa M. , Wang Shu-Ching Mary , Eriksson Natalie A. , Myers Stephen A. , Murray Lauren A. , Muscat George E. O.
Published: December 2010

We demonstrate that chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) mRNA is more abundantly expressed (than COUP-TFI mRNA) in skeletal muscle C2C12 cells and in (type I and II) skeletal muscle tissue from C57BL/10 mice. Consequently, we have utilized the ABI TaqMan Low Density Array (TLDA) platform to analyze gene expression changes specifically attributable to ectopic COUP-TFII (relative to vector only) expression in muscle cells. Utilizing a TLDA-based platform and 5 internal controls, we analyze the entire NR superfamily, 96 critical metabolic genes, and 48 important myogenic regulatory genes on the TLDA platform utilizing 5 internal controls. The low density arrays were analyzed by rigorous statistical analysis (with Genorm normalization, Bioconductor R, and the Empirical Bayes statistic) using the (integromics) statminer software. In addition, we validated the differentially expressed patho-physiologically relevant gene (identified on the TLDA platform) glucose transporter type 4 (Glut4). We demonstrated that COUP-TFII expression increased the steady state levels of Glut4 mRNA and protein, while ectopic expression of truncated COUP-TFII lacking helix 12 (COUP-TFΔH12) reduced Glut4 mRNA expression in C2C12 cells. Moreover, COUP-TFII expression trans-activated the Glut4 promoter (−997/+3), and ChIP analysis identified selective recruitment of COUP-TFII to a region encompassing a highly conserved SP1 binding site (in mouse, rat, and human) at nt positions −131/−118. Mutation of the SpI site ablated COUP-TFII mediated trans-activation of the Glut4 promoter. In conclusion, this study demonstrates that in skeletal muscle cells, COUP-TFII regulates several nuclear hormone receptors, and critical metabolic and muscle specific genes.
Selective Vulnerability of Neurons in Layer II of the Entorhinal Cortex during Aging and Alzheimer's Disease
Authors: Stranahan Alexis M. , Mattson Mark P.
Published: December 2010

All neurons are not created equal. Certain cell populations in specific brain regions are more susceptible to age-related changes that initiate regional and system-level dysfunction. In this respect, neurons in layer II of the entorhinal cortex are selectively vulnerable in aging and Alzheimer's disease (AD). This paper will cover several hypotheses that attempt to account for age-related alterations among this cell population. We consider whether specific developmental, anatomical, or biochemical features of neurons in layer II of the entorhinal cortex contribute to their particular sensitivity to aging and AD. The entorhinal cortex is a functionally heterogeneous environment, and we will also review data suggesting that, within the entorhinal cortex, there is subregional specificity for molecular alterations that may initiate cognitive decline. Taken together, the existing data point to a regional cascade in which entorhinal cortical alterations directly contribute to downstream changes in its primary afferent region, the hippocampus.
Body Mass and Fat Mass in Refractory Asthma: An Observational 1 Year Follow-Up Study
Authors: Bafadhel Mona , Singapuri Amisha , Terry Sarah , Hargadon Beverley , Monteiro William , Green Ruth H. , Bradding Peter H. , Wardlaw Andrew J. , Pavord Ian D. , Brightling Christopher E.
Published: December 2010

Background. Asthma and obesity are common; however the impact of obesity upon asthma remains uncertain. Objectives. To assess relationships between obesity and fat mass with airway inflammation, lung function, and disease control in patients with refractory asthma. Methods. 151 refractory asthma patients were characterised for measures of airway inflammation, lung function, Juniper asthma control questionnaire (JACQ), body mass index (BMI), and fat mass index (FMI) derived from dual energy X-ray absorptiometry. Patients were reassessed over 12 months. Results. 74% of patients had an elevated BMI. BMI and FMI correlated (r=0.9, P<.001). FMI and JACQ correlated in men (r=0.3, P=.01). After 12 months 23% lost weight. Weight change over 12 months correlated with FEV1 change (r=−0.3, P=.03), but not with change in JACQ or exacerbations. Conclusion. Increased fat mass is common in refractory asthma and is associated with asthma symptom control in men. Loss of weight is associated with improvement in lung function in refractory asthma.
Determining the Impact of the AM-Mycorrhizosphere on “Dwarf” Sunflower Zn Uptake and Soil-Zn Bioavailability
Authors: Audet Patrick , Charest Christiane
Published: December 2010

An in vivo compartmental pot greenhouse experiment involving “dwarf” sunflower and an arbuscular mycorrhizal (AM) fungus was designed to assess the contribution of non-AM roots (rhizosphere), AM roots and extraradical hyphae (mycorrhizosphere), or strictly extraradical hyphae (hyphosphere) on plant growth, plant metal uptake, and soil parameters using the micronutrient zinc (Zn) as a typical metal contaminant. We observed that, at high soil-Zn concentrations, the mycorrhizosphere treatments had lower Zn concentrations (especially in shoots and flowers) and a lower incidence of leaf chlorosis than the rhizosphere treatments. These phytoprotective effects are believed to be related to AM-induced biosorption processes that reduce soil metal bioavailability to delay the onset of plant metal toxicity. We also observed that the presence of extraradical hyphae causes a slight alkalinisation of the proximal soil environment whereas roots tended to acidify it, this having significant consequences toward metal bioavailability. Altogether, the AM symbiosis is considered to be a key component of ecosystem function involved in buffering plant growth conditions due to the processes of metal biosorption and hyphal alkalinisation which could contribute in enhancing the soil's resiliency.
Evaluation of Serum Testosterone, Progesterone, Seminal Antisperm Antibody, and Fructose Levels among Jordanian Males with a History of Infertility
Authors: Al-Daghistani Hala I. , Hamad Abdul-Wahab R. , Abdel-Dayem Muna , Al-Swaifi Mohammad , Abu Zaid Mohammad
Published: December 2010

Due to the biochemical complexity of seminal fluid, we attempt to study the possible correlation between fructose, which is secreted under the effect of androgen hormone, and autoimmunity, which might play a role in varicocele associated infertility, in reducing sperm motility. Seminal fructose, antisperm antibodies (ASAs) and blood steroids hormones (testosterone and progesterone) levels were measured in 66 infertile males with varicocele and 84 without varicocele referred for fertility treatment. Seminal analysis was performed with biochemical measurements of seminal fructose and mixed agglutination reaction (MAR) for ASA. Serum levels of progesterone and testosterone were estimated using a competitive chemoluminescent enzyme immunoassay. The mean values for serum testosterone were380.74±24.331,365.9±16.55, and367.5±21.8 ng/dl, progesterone0.325±0.243,0.341±0.022, and0.357  ±  0.0306 ng/ml, and seminal plasma fructose359.6  ±  26.75,315.6  ±  13.08, and332.08  ±  24.38 mg/dl in males with varicocele, without varicocele, and fertile males, respectively. A significant high level of testosterone was observed within varicocele group (P=.001). This result showed that testosterone may play a role as an infertility determinant in subjects with varicocele. ASA was detected in 18 (26.47%) of cases with varicocele, 20 (38.46%) without varicocele, and in 16 (32.0%) fertile men. Cases with ASAs associated with low sperm motility morphology. An inverse correlation between sperm-bound antibodies and viscosity has been shown (P=.017). ASA showed some significant inverse relations with ages, durations of infertility, and viscosity (P<.05). In addition, a significant correlation was observed between ASA positive seminal plasma and testosterone concentration among infertile cases (with or without varicocele) and fertile (P<.05). Our results suggest a relationship between testicular steroid hormone levels with autoimmunity and sperm antibodies which influence the motility of ejaculated spermatozoa among Jordanian infertile males.
ACE Inhibitor-Induced Angioedema of the Bowel
Authors: Campbell Tabitha , Peckler Bradley , Hackstadt Raleigh David , Payor Austin
Published: December 2010

Angiotensin converting enzyme inhibitor ACEI-induced angioedema of the intestine is a rare occurrence and often unrecognized complication of ACEI. We present a case of a 45-year-old Hispanic female with angioedema of the small bowel progressing to facial and oral pharyngeal angioedema. Patients are typically middle-aged females on ACEI therapy who present to the emergency department with abdominal pain, nausea, vomiting, and diarrhea. This is a diagnosis of exclusion, and physicians must have a high index of suspicion to make the diagnosis. Symptoms typically resolve within 24–48 hours after ACE inhibitor withdrawal. Recognizing these signs and symptoms, and discontinuing the medication, can save a patient from unnecessary, costly, and invasive procedures.
Strong Convergence Theorems for a Countable Family of Lipschitzian Mappings
Authors: Nilsrakoo Weerayuth , Saejung Satit
Published: December 2010

We modify the iterative method introduced by Kim and Xu (2006) for a countable family of Lipschitzian mappings by the hybrid method of Takahashi et al. (2008). Our results include recent ones concerning asymptotically nonexpansive mappings due to Plubtieng and Ungchittrakool (2007) and Zegeye and Shahzad (2008, 2010) as special cases.
Subtle Radiological Features of Splenic Avulsion following Abdominal Trauma
Authors: Rehim S. A. , Dagash H. , Godbole P. P. , Raghavan A. , Murthi G. V.
Published: December 2010

Splenic trauma in children following blunt abdominal injury is usually treated by nonoperative management (NOM). Splenectomy following abdominal trauma is rare in children. NOM is successful as in the majority of instances the injury to the spleen is contained within its capsule or a localised haematoma. Rarely, the spleen may suffer from an avulsion injury that causes severe uncontrollable bleeding and necessitates an emergency laparotomy and splenectomy. We report two cases of children requiring splenectomy following severe blunt abdominal injury. In both instances emergency laparotomy was undertaken for uncontrollable bleeding despite resuscitation. The operating team was unaware of the precise source of bleeding preoperatively. Retrospective review of the computed tomography (CT) scans revealed subtle radiological features that indicate splenic avulsion. We wish to highlight these radiological features of splenic avulsion as they can help to focus management decisions regarding the need/timing for a laparotomy following blunt abdominal trauma in children.
Simultaneous Nasopharyngeal Carriage of Two Pneumococcal Multilocus Sequence Types with a Serotype 3 Phenotype
Authors: Inverarity Donald , Diggle Mathew , Ure Roisin , Santana-Hernandez Diego , Altstadt Peter , Mitchell Timothy , Edwards Giles
Published: December 2010

Knowledge of the epidemiology of pneumococcal disease in Bolivia is sparse, and Multilocus Sequence Typing (MLST) of isolates has not been previously possible. Beni state has until recently been a geographically isolated region of the Bolivian Amazon basin and is a region of significant poverty. During June and July 2007, we performed a pneumococcal carriage study recruiting over 600 schoolchildren in two towns in the Beni state. Here, we describe the unique identification of simultaneous nasopharyngeal carriage of two pneumococcal multilocus sequence types with a serotype 3 phenotype within a single subject.
Thickness Dependence of Optoelectrical Properties of Mo‐Doped In2O3 Films Deposited on Polyethersulfone Substrates by Ion‐Beam‐Assisted Evaporation
Authors: Kuo Chin-Chiuan , Liu Chi-Chang , Jeng Yaug-Fea , Lin Chung-Chih , Liou Yeuh-Yeong , He Ju-Liang
Published: December 2010

Indium molybdenum oxide (IMO) films were deposited onto the polyethersulfone (PES) substrates by ion‐beam‐assisted evaporation (IBAE) deposition at low temperature in this study. The effects of film thickness on their optical and electrical properties were investigated. The results show that the deposited IMO films exhibit a preferred orientation of B(222). The electrical resistivity of the deposited film initially reduces then subsequently increases with film thickness. The IMO film with the lowest resistivity of 7.61 × 10−4 ohm‐cm has been achieved when the film thickness is 120 nm. It exhibits a satisfactory surface roughness Rpv of 8.75 nm and an average visible transmittance of 78.7%.
Postpartum Pneumomediastinum: an Uncommon Cause for Chest Pain
Authors: Revicky Vladimir , Simpson Paul , Fraser David
Published: December 2010

This case report refers to a 32‐year‐old primiparous woman with a mild asthma, who had a normal vaginal delivery in a birthing pool and developed an acute postpartum chest pain due to pneumomediastinum and subcutaneous chest emphysema. After 72 hours of observation, she was discharged home without any residual symptoms.
Pilot Study of Inhaled Aerosols Targeted via Magnetic Alignment of High Aspect Ratio Particles in Rabbits
Authors: Redman Gillian E. S. , Martin Andrew R. , Waszak Paul , Thompson Richard B. , Cheung Po-Yin , Thébaud Bernard , Finlay Warren H.
Published: December 2010

Recently, inhaled pharmaceutical aerosols have seen increased investigation in the treatment of lung cancer, where the inability to deliver adequate therapeutic drug concentrations to tumour sites may be overcome with improved targeted delivery to the site of the tumour. In this study, the feasibility of magnetically targeted delivery of high aspect ratio particles loaded with iron oxide nanoparticles was studied in 19 New Zealand White rabbits. Half of the exposed rabbits had a magnetic field placed externally over their right lung. Iron sensitive magnetic resonance images of the lungs were acquired to determine the iron concentrations in the right and left lung of each animal. The right/left ratio increased in the middle and basal regions of the lung where, due to the morphology of the rabbit lung, this method of targeting is most effective. With further optimization, this technique could be an effective method for increasing the dose of drug delivered to a specific site within the lung.
Contact Heterogeneity and Phylodynamics: How Contact Networks Shape Parasite Evolutionary Trees
Authors: O'Dea Eamon B. , Wilke Claus O.
Published: December 2010

The inference of population dynamics from molecular sequence data is becoming an important new method for the surveillance of infectious diseases. Here, we examine how heterogeneity in contact shapes the genealogies of parasitic agents. Using extensive simulations, we find that contact heterogeneity can have a strong effect on how the structure of genealogies reflects epidemiologically relevant quantities such as the proportion of a population that is infected. Comparing the simulations to BEAST reconstructions, we also find that contact heterogeneity can increase the number of sequence isolates required to estimate these quantities over the course of an epidemic. Our results suggest that data about contact-network structure will be required in addition to sequence data for accurate estimation of a parasitic agent's genealogy. We conclude that network models will be important for progress in this area.
Clinical Characteristics of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in North Indian Population of HIV/AIDS Patients Receiving HAART
Authors: Karmakar Suman , Sharma Surendra K. , Vashishtha Richa , Sharma Abhishek , Ranjan Sanjay , Gupta Deepak , Sreenivas Vishnubhatla , Sinha Sanjeev , Biswas Ashutosh , Gulati Vinay
Published: December 2010

Background & Objective. IRIS is an important complication that occurs during management of HIV-TB coinfection and it poses difficulty in diagnosis. Previous studies have reported variable incidence of IRIS. The present study was undertaken to describe the pattern of TB-associated IRIS using recently proposed consensus case-definitions for TB-IRIS for its use in resource-limited settings.Methods. A prospective analysis of ART-naïve adults started on HAART from November, 2008 to May, 2010 was done in a tertiary care hospital in north India. A total 224 patients divided into two groups, one with HIV-TB and the other with HIV alone, were followedup for a minimum period of 3 months. The diagnosis of TB was categorised as ‘‘definitive’’ and ‘‘probable’’.Results. Out of a total of 224 patients, 203 completed followup. Paradoxical TB-IRIS occurred in 5 of 123 (4%) HIV-TB patients while 6 of 80 (7.5%) HIV patients developed ART-associated TB. A reduction in plasma viral load was significantly (P=.016) associated with paradoxical TB-IRIS. No identifiable risk factors were associated with the development of ART-associated TB.Conclusion. The consensus case-definitions are useful tools in the diagnosis of TB-associated IRIS. High index of clinical suspicion is required for an early diagnosis.
Ewing Sarcoma: An Eponym Window to History
Authors: Cripe Timothy P.
Published: December 2010

Ewing sarcoma was named after James R. Ewing, an eminent American pathologist at Cornell who described the first cases in 1921. Although he is best remembered for this singular achievement, Ewing's contributions to the study of cancer were far more profound and influential. He essentially launched oncology as a discipline with the publication of his seminal textbook and founded the major American cancer societies that exist today. His vision of comprehensive cancer centers still drives our research infrastructure. Since his initial report, these organizations have helped us achieve numerous milestones in understanding and treating patients with Ewing sarcoma.
Gaze Perception Develops Atypically in Children with Autism
Authors: Webster Simon , Potter Douglas D.
Published: December 2010

The Mindblindness model is the main model of social cognitive development in autism. This model assumes that eye direction detection and eye contact detection develop typically in autism (Baron-Cohen, 1995). The model's assumption of maturational development implies that when these skills are abnormal, they must either be absent or developmentally delayed. In contrast, the atypical modularisation hypothesis predicts that these skills can develop deviantly—successfully but atypically—in children with autism. Two computer-based tasks were used to assess eye direction detection and eye contact detection in children with autism and in typically developing children. These skills were developmentally deviant in children with autism. The findings support a model of social cognition in autism that accounts for developmental processes.
Phase Transition Behavior of HPMC-AA and Preparation of HPMC-PAA Nanogels
Authors: Yao Risheng , Xu Jiajia , Lu Xihua , Deng Shengsong
Published: December 2010

The lower critical solution temperature (LCST) of hydroxypropyl methylcellulose (HPMC) under mixing with acrylic acid (AA) monomer has been studied by turbidity measurements. It has been found that the LCST of the HPMC was drastically reduced from 60°C to 38°C with the increase of the concentration of AA, while the HPMC is kept at 0.5 wt%. The driving force shifting the LCST is attributed to the hydrogen bonding and hydrophobic interaction of the molecules. Then surfactant-free HPMC-PAA nanogels have been synthesized via the polymerization of AA monomer with the collapsed HPMC as a template or core at their LCST, using KPS and TEMED as redox initiator in the presence of BIS as cross-linking agent. HPMC-PAA nanogels have 50~150  nm diameters characterized by transmission electron microscope and dynamic light scattering. The HPMC-PAA nanogels exhibit the temperature phase transition behaviors, and these nanogels' volume phase transition temperature is close to the LCST of HPMC/AA system.
Recurrent Neurotropic Chloroma: Report of a Case and Review of the Literature
Authors: Bakst Richard , Jakubowski Ann , Yahalom Joachim
Published: December 2010

We are reporting a case of a young woman with acute myelogenous leukemia status postallogeneic transplantation who developed multiply recurrent chloromas occurring along peripheral nerves in the absence of bone marrow relapse, all treated with radiation therapy. The patient is currently free of disease nearly four years after her first posttransplant chloroma. The case presented is unique for its isolated peripheral nervous system involvement, rare posttransplant occurrence, and indolent course without marrow relapse despite multiple extramedullary recurrences.
Forecasting the Population-Level Impact of Reductions in HIV Antiretroviral Therapy in Papua New Guinea
Authors: Gray Richard T. , Zhang Lei , Lupiwa Tony , Wilson David P.
Published: December 2010

Papua New Guinea (PNG) recently did not secure external funding for the continuation of its antiretroviral treatment (ART) programs meaning that supplies of HIV drugs for the estimated 38,000 people living with HIV in PNG could be completely depleted during 2010. Using a mathematical model of HIV transmission calibrated to available HIV epidemiology data from PNG, we evaluated the expected population-level impact of reductions in ART availability. If the number of people on ART falls to 10% of its current level, then there could be an approximately doubling in annual incidence and an additional 12,848 AIDS-related deaths (100.7% increase) over the next 5 years; if ART provision is halved, then annual incidence would increase by ~68%, and there would be an additional ~10,936 AIDS-related deaths (85.7% increase). These results highlight that maintenance of ART and associated services through external funding is essential for the health and well-being of HIV-positive people in PNG.
Surgical Approaches to Create Murine Models of Human Wound Healing
Authors: Wong Victor W. , Sorkin Michael , Glotzbach Jason P. , Longaker Michael T. , Gurtner Geoffrey C.
Published: December 2010

Wound repair is a complex biologic process which becomes abnormal in numerous disease states. Although in vitro models have been important in identifying critical repair pathways in specific cell populations, in vivo models are necessary to obtain a more comprehensive and pertinent understanding of human wound healing. The laboratory mouse has long been the most common animal research tool and numerous transgenic strains and models have been developed to help researchers study the molecular pathways involved in wound repair and regeneration. This paper aims to highlight common surgical mouse models of cutaneous disease and to provide investigators with a better understanding of the benefits and limitations of these models for translational applications.
Genomic Instability in Mice Is Greater in Fanconi Anemia Caused by Deficiency of Fancd2 than Fancg
Authors: Reliene Ramune , Yamamoto Mitsuko L. , Rao P. Nagesh , Schiestl Robert H.
Published: December 2010

Fanconi anemia (FA) results from mutations in the FANC genes and is characterized by bone marrow failure, birth defects, and a high incidence of cancer. FANCG is a part of the FA core complex that is responsible for monoubiquitination of FANCD2 and FANCI. The precise role of the FA pathway is not well understood, although it may be involved in homologous recombination (HR), nonhomologous end joining, and translesion synthesis (TLS). Fancd2−/– mice have a more severe phenotype than Fancg−/–, and other FA core complex–deficient mice, although both Fancg and Fancd2 belong to the same FA pathway. We hypothesized that Fancd2 deficiency results in a more severe phenotype because Fancd2 also has a FA pathway-independent function in the maintenance of genomic integrity. To test this hypothesis, we determined the level of DNA damage and genomic instability in Fancd2−/−, Fancg−/–, and wild-type controls. Fancd2−/− mice displayed a higher magnitude of chromosomal breakage and micronucleus formation than the wild-type or Fancg−/− mice. Also, DNA strand breaks were increased in Fancd2−/− but not in Fancg−/− mice. In addition, Fancd2−/– mice displayed an elevated frequency of DNA deletions, resulting from HR at the endogenous pun locus. In contrast, in Fancg−/– mice, the frequency of DNA deletions was decreased. Thus, Fancd2 but not Fancg deficiency results in elevated chromosomal/DNA breakage and permanent genome rearrangements. This provides evidence that Fancd2 plays an additional role in the maintenance of genomic stability than Fancg, which might explain the higher predisposition to cancer seen in the Fancd2−/− mice. Cancer Res; 70(23); 9703–10. ©2010 AACR.
Increase of Plasma VEGF after Intravenous Administration of Bevacizumab Is Predicted by a Pharmacokinetic Model
Authors: Stefanini Marianne O. , Wu Florence T. H. , Mac Gabhann Feilim , Popel Aleksander S.
Published: December 2010

Vascular endothelial growth factor (VEGF) is one of the most potent cytokines targeted in antiangiogenic therapies. Bevacizumab, a recombinant humanized monoclonal antibody to VEGF, is being used clinically in combination with chemotherapy for colorectal, non–small cell lung and breast cancers, and as a single agent for glioblastoma and is being tested for other types of cancer in numerous clinical trials. It has been reported that the intravenous injection of bevacizumab leads to an increase of plasma VEGF concentration in cancer patients. The mechanism responsible for this counterintuitive increase has not been elucidated, although several hypotheses have been proposed. We use a multiscale systems biology approach to address this problem. We have constructed a whole-body pharmacokinetic model comprising three compartments: blood, normal tissue, and tumor tissue. Molecular interactions among VEGF-A family members, their major receptors, the extracellular matrix, and an anti-VEGF ligand are considered for each compartment. Diffusible molecules extravasate, intravasate, are removed from the healthy tissue through the lymphatics, and are cleared from the blood. Cancer Res; 70(23); 9886–94. ©2010 AACR.
Sphingosine-1-Phosphate Activates the AKT Pathway to Protect Small Intestines from Radiation-Induced Endothelial Apoptosis
Authors: Bonnaud Stéphanie , Niaudet Colin , Legoux François , Corre Isabelle , Delpon Gregory , Saulquin Xavier , Fuks Zvi , Gaugler Marie-Hélène , Kolesnick Richard , Paris François
Published: December 2010

A previous in vitro study showed that sphingosine-1-phosphate (S1P), a ceramide antagonist, preserved endothelial cells in culture from radiation-induced apoptosis. We proposed to validate the role of S1P in tissue radioprotection by inhibiting acute gastrointestinal (GI) syndrome induced by endothelial cell apoptosis after high dose of radiation. Retro-orbital S1P was injected in mice exposed to 15 Gy, a dose-inducing GI syndrome within 10 days. Overall survival and apoptosis on intestines sections were studied. Intestinal cell type targeted by S1P and early molecular survival pathways were researched using irradiated in vitro cell models and in vivo mouse models. We showed that retro-orbital S1P injection before irradiation prevented GI syndrome by inhibiting endothelium collapse. We defined endothelium as a specific therapeutic target because only these cells and not intestinal epithelial cells, or B and T lymphocytes, were protected. Pharmacologic approaches using AKT inhibitor and pertussis toxin established that S1P affords endothelial cell protection in vitro and in vivo through a mechanism involving AKT and 7-pass transmembrane receptors coupled to Gi proteins. Our results provide strong pharmacologic and mechanistic proofs that S1P protects endothelial cells against acute radiation enteropathy. Cancer Res; 70(23); 9905–15. ©2010 AACR.
Integrity of SOS1/EPS8/ABI1 Tri-Complex Determines Ovarian Cancer Metastasis
Authors: Chen Huijun , Wu Xufeng , Pan Zhixing K. , Huang Shuang
Published: December 2010

Ovarian cancer is mainly confined in peritoneal cavity and its metastasis is often associated with the formation of malignant ascites. As lysophosphatidic acid (LPA) is present at high levels in ascites of ovarian cancer patients and potently stimulates cell migration, we reason that LPA-stimulated cell migration may play an important role in ovarian cancer metastasis. Here, we show that only ovarian cancer cell lines with LPA migratory response undergo peritoneal metastatic colonization. LPA-stimulated cell migration is required for metastatic colonization because knockdown of LPA receptor subtype 1 (LPAR1) abolishes this event. However, the difference in metastatic potentials is not caused by the absence of LPAR1 because both metastatic and nonmetastatic lines express similar levels of LPAR1. Instead, we find that LPA can activate Rac only in metastatic cells and that metastatic colonization of ovarian cancer cells necessitates Rac activity. These results thus suggest that LPA-induced Rac activation is a prerequisite for ovarian cancer metastasis. In metastatic cells, Rac activation is facilitated by SOS1/EPS8/ABI1 tri-complex and the integrity of this tri-complex is essential for LPA-stimulated cell migration and metastatic colonization. We show that at least 1 member of SOS1/EPS8/ABI1 tri-complex is absent in nonmetastatic ovarian cancer cells and reexpressing the missing one conferred them with metastatic capability. Importantly, coexpression of SOS1, EPS8, and ABI1, but not of any individual member of SOS1/EPS8/ABI1 tri-complex, correlates with advanced stages and shorter survival of ovarian cancer patients. Our study implicates that the integrity of SOS1/EPS8/ABI1 tri-complex is a determinant of ovarian cancer metastasis. Cancer Res; 70(23); 9979–90. ©2010 AACR.
MEK1/2 Inhibitors AS703026 and AZD6244 May Be Potential Therapies for KRAS Mutated Colorectal Cancer That Is Resistant to EGFR Monoclonal Antibody Therapy
Authors: Yoon Juyong , Koo Kyoung-Hwa , Choi Kang-Yell
Published: December 2010

Epidermal growth factor receptor (EGFR) monoclonal antibodies (mAb) are used widely to treat metastatic colorectal cancer (mCRC) patients, but it is now clear that patients harboring K-ras mutation are resistant to EGFR mAbs such as cetuximab (Erbitux) and panitumumab (Vectibix). For this reason, current recommendations for patient care involve diagnosing the K-ras mutational status of patients prior to EGFR mAb therapy. In this study, we investigated the ability of two MEK inhibitors currently in clinical trials, AS703026 and AZD6244, to address the challenge posed by the resistance of K-ras mutated colorectal cancers to EGFR mAb. AS703026 and AZD6244 were tested in various cell-based assays and tumor xenograft studies, focusing on isogenic human colorectal tumor cell lines that expressed only WT or mutant K-Ras (D-WT or D-MUT). The EGFR mAb cetuximab inhibited the Ras-ERK pathway and proliferation of D-WT cells in vitro and in vivo, but it did not inhibit proliferation of D-MUT cells in either setting. In contrast, AS703026 and AZD6244 effectively inhibited the growth of D-MUT cells in vitro and in vivo by specific inhibition of the key MEK downstream target kinase ERK. Inhibition of MEK by AS703026 or AZD6244 also suppressed cetuximab-resistant colorectal cancer cells attributed to K-ras mutation both in vitro and in vivo. Our findings offer proof-of-concept for the use of MEK inhibitors as an effective therapy in K-ras mutated CRC. Cancer Res; 71(2); 445–53. ©2010 AACR.
Effect of Emphysema on Lung Cancer Risk in Smokers: A Computed Tomography–Based Assessment
Authors: Li Yan , Swensen Stephen J. , Karabekmez Leman Günbey , Marks Randolph S. , Stoddard Shawn M. , Jiang Ruoxiang , Worra Joel B. , Zhang Fang , Midthun David E. , de Andrade Mariza , Song Yong , Yang Ping
Published: December 2010

The contribution of emphysema to lung cancer risk has been recognized, but the effect size needs to be further defined. In this study, 565 primary lung cancer cases were enrolled though a prospective lung cancer cohort at Mayo Clinic, and 450 controls were smokers participating in a lung cancer screening study in the same institution using spiral computed tomography (CT). Cases and controls were frequency matched on age, gender, race, smoking status, and residential region. CT imaging using standard protocol at the time of lung cancer diagnosis (case) or during the study (control) was assessed for emphysema by visual scoring CT analysis as a percentage of lung tissue destroyed. The clinical definition of emphysema was the diagnosis recorded in the medical documentation. Using multiple logistic regression models, emphysema (≥5% on CT) was found to be associated with a 3.8-fold increased lung cancer risk in Caucasians, with higher risk in subgroups of younger (<65 years old, OR = 4.64), heavy smokers (≥40 pack-years, OR = 4.46), and small-cell lung cancer (OR = 5.62). When using >0% or ≥10% emphysema on CT, lung cancer risk was 2.79-fold or 3.33-fold higher than controls. Compared with CT evaluation (using criterion ≥5%), the sensitivity, specificity, positive and negative predictive values, and the accuracy of the clinical diagnosis for emphysema in controls were 19%, 98%, 73%, 84%, and 83%, respectively. These results imply that an accurate evaluation of emphysema could help reliably identify individuals at greater risk of lung cancer among smokers. Cancer Prev Res; 4(1); 43–50. ©2010 AACR.
Detección sistemática de la fenilcetonuria
Authors: Bodamer Olaf A.
Published: December 2010

La detección sistemática de recién nacidos para indagar la presencia de fenilcetonuria (FCU) se inició con Robert Guthrie (1916–1995), quien desarrolló la prueba de inhibición bacteriana para el análisis semicuantitativo de fenilalanina, que constituía la primera prueba idónea para un análisis de alto rendimiento. Además, introdujo la ‘tarjeta de papel filtro de Guthrie’ como medio de transporte de la sangre desecada, procedimiento que todavía se utiliza en la actualidad. Teniendo en cuenta el potencial de su enfoque para el diagnóstico precoz y el hecho de que una dieta pobre en fenilalanina prevenía las secuelas neurológicas de la FCU no tratada, Robert Guthrie llegó a ser el primer y máximo abogado de la detección sistemática de recién nacidos para indagar la presencia de FCU. Consecutivamente al primer programa de detección sistemática de recién nacidos para FCU en Buffalo, N.Y., EE.UU. en la década de los 60, se iniciaron otros programas de detección sistemática de recién nacidos en todo el mundo en las décadas de los 60 y los 70. Desde entonces, la detección sistemática de recién nacidos ha sido admitida como una importante medida de salud pública y la mayoría de los países tienen en curso programas de detección sistemática de recién nacidos para la FCU y otros errores congénitos del metabolismo. Desde los primeros programas se admite que el diagnóstico precoz de la FCU y el inicio subsiguiente de una dieta pobre en fenilalanina permite la obtención de desenlaces neurológicos normales, en contraste con el retraso mental grave de la FCU no tratada. Los laboratorios que practican actualmente la detección sistemática de recién nacidos utilizan análisis fotométricos o espectrometría de masas en tándem para el análisis de la fenilalanina en lugar de la prueba de inhibición bacteriana. Esto ha dado lugar a un incremento del número de casos con hiperfenilalaninemia que, a menudo, no requieren tratamiento dietético. Todo nivel elevado de fenilalanina en un recién nacido obliga a la obtención de una segunda muestra para repetir el análisis de fenilalanina y tirosina. La confirmación de niveles elevados de fenilalanina junto a niveles bajos o normales de tirosina se sigue de la realización de un análisis de pterinas urinarias y de la actividad de la dihidropterina reductasa en los eritrocitos para excluir un error congénito del metabolismo de la biopterina. En todo recién nacido cuyos niveles hemáticos de fenilalanina rebasen los 6 mg/dl debe realizarse una prueba de carga de tetrahidrobiopterina y dar comienzo a un tratamiento dietético. El nivel en el cual se inicia la terapéutica dietética puede diferir entre EE.UU., Reino Unido y Europa continental.
Gamma Knife Robotic Microradiosurgery for Benign Skull Base Meningiomas: Tumor Shrinkage May Depend on the Amount of Radiation Energy Delivered per Lesion Volume (Unit Energy)
Authors: Hayashi Motohiro , Chernov Mikhail , Tamura Noriko , Izawa Masahiro , Muragaki Yoshihiro , Iseki Hiroshi , Okada Yoshikazu , Takakura Kintomo
Published: December 2010

Background/Aims: The objective of the present study was the evaluation of the effectiveness of robotic microradiosurgery of skull base meningiomas using Leksell Gamma Knife model C with an automatic positioning system. Methods: The results of the management of 66 tumors were analyzed retrospectively. Their volume varied from 0.3 to 50.6 cm3 (mean = 6.6). The treatment plan was based on the use of multiple small isocenters compactly positioned within the border of the lesion with resultant improved homogeneity of high-dose distribution, increased average dose within the target and sharp dose fall outside the treated volume. The marginal dose varied from 10 to 14 Gy (mean = 12). The length of follow-up ranged from 26 to 80 months (mean = 46). Results: The overall tumor growth control was 99%. Reduction of the mass volume was marked in 54 patients (82%), and in 15 of them it constituted ≧50%. In other 11 cases (17%) stabilization of the lesion growth was noted. The shrinkage rate significantly correlated with amount of radiation energy delivered per tumor volume, designated as unit energy (p = 0.007). One meningioma (1%) regrew 3.5 years after radiosurgery. The treatment-related morbidity was limited to transient abducens nerve palsy in 1 patient (1%). Conclusion: Application of the concept of Gamma Knife robotic microradiosurgery for the management of skull base meningiomas may change the paradigm of their treatment from stabilization of growth to reduction of the volume of the neoplasm. The tumor shrinkage rate may depend on the amount of radiation energy delivered per lesion volume (unit energy).