bluuebunny/crossref_metadata_2025 huggingface dataset:
YmoA negatively controls the expression of insecticidal genes in Yersinia enterocolitica
Authors: Starke Mandy , Fuchs Thilo M.
Published: February 2014

Yersinia enterocolitica is toxic towards invertebrates due to the presence of the toxin complex (tc) genes that are activated by the thermolabile regulator TcaR2. In the search for further regulatory factors involved in insecticidal gene expression, the modulator of yersinial virulence, YmoA, was identified to silence all tc genes of the Y. enterocolitica strain W22703 (biovar 2, serovar O:9). Using promoter fusions with the luciferase reporter, we found that the deletion of ymoA results in elevated transcription of tcaR1, tcaR2, tcaA, tcaB, tcaC, tccC1 and tccC2 at both 15°C and 37°C. Complementation by episomal ymoA significantly reduced tc gene expression, thus validating the inhibitory activity of YmoA on the production of insecticidal proteins. YmoA contributes to the binding properties of H‐NS to the tc promoters by forming a complex with this nucleoid‐associated protein, and this complex not only binds to the upstream regions of all tc genes, but also to intragenic sites of tcaA and tcaB that play an important role in controlling the expression of both genes. At low temperature, the intracellular amount of thermostable YmoA is not reduced, but the repressor is less functional. These data point to H‐NS/YmoA as an antagonist of the inducer TcaR2.
How accurate is self‐reported BMI?
Authors: Gosse M. A.
Published: February 2014

Body mass index (BMI) is a common research measure used to allocate the weight of study participants into broad groups, typically underweight, normal weight, overweight and obese categories. Some studies measure the actual height and weight of participants to calculate a measured BMI score but many rely on self‐reported height and weight. This paper examines the accuracy of BMI categories based on self‐reported height and weight compared with measured data. It critiques the use of mean differences between measured and self‐reported BMI scores as a measure of self‐reported BMI accuracy. It also demonstrates how reliance on proportion changes in BMI categories as a result of using self‐reported BMI scores fails to demonstrate the extent that participants are misclassified into an incorrect BMI category. The paper also examines actual rates of misclassification for BMI categories, using the obesity category as an example. The association of sociodemographic factors with BMI accuracy is also considered, as well as the technical feasibility of using correction factors to improve the accuracy of self‐reported BMI. The main finding is that self‐reported BMI score and associated BMI category tend to be underestimated. Also, the self‐reported BMI misclassification rate appears to increase as measured BMI score increases, with obese study participants in particular being most likely to be misclassified. No correction method has been found that will adjust accurately for misclassification based on self‐reported BMI. The analysis suggests that self‐reported BMI may have major limitations for use in public health research and policy‐making decisions.
Diet modelling: How it can inform the development of dietary recommendations and public health policy
Authors: Buttriss J. L. , Briend A. , Darmon N. , Ferguson E. L. , Maillot M. , Lluch A.
Published: February 2014

With the global population expected to increase to 9 billion by 2050 coupled with concerns about food security in relation to climate change and increasing prosperity in many parts of the world causing desire for a less monotonous diet, efficient use of resources such as food becomes ever more important. While the prevalence of obesity is a cause for concern in many parts of the world, many people still go to bed hungry, and in many communities, obesity co‐exists with poor diet quality. The result is a series of complex and challenging nutrition problems, such as the access to nutritionally adequate and affordable diets and the development of dietary recommendations. Diet modelling is a useful tool to help identify solutions to such complex questions and this paper summarises a session on this topic at the International Congress of Nutrition that took place in September 2013.
The small phytoplasma virulence effector SAP11 contains distinct domains required for nuclear targeting and CIN‐TCP binding and destabilization
Authors: Sugio Akiko , MacLean Allyson M. , Hogenhout Saskia A.
Published: February 2014

Phytoplasmas are insect‐transmitted bacterial phytopathogens that secrete virulence effectors and induce changes in the architecture and defense response of their plant hosts. We previously demonstrated that the small (± 10 kDa) virulence effector SAP11 of Aster Yellows phytoplasma strain Witches' Broom (AY‐WB) binds and destabilizes Arabidopsis CIN (CINCINNATA) TCP (TEOSINTE‐BRANCHED, CYCLOIDEA, PROLIFERATION FACTOR 1 AND 2) transcription factors, resulting in dramatic changes in leaf morphogenesis and increased susceptibility to phytoplasma insect vectors. SAP11 contains a bipartite nuclear localization signal (NLS) that targets this effector to plant cell nuclei.

To further understand how SAP11 functions, we assessed the involvement of SAP11 regions in TCP binding and destabilization using a series of mutants.

SAP11 mutants lacking the entire N‐terminal domain, including the NLS, interacted with TCPs but did not destabilize them. SAP11 mutants lacking the C‐terminal domain were impaired in both binding and destabilization of TCPs. These SAP11 mutants did not alter leaf morphogenesis. A SAP11 mutant that did not accumulate in plant nuclei (SAP11ΔNLS‐NES) was able to bind and destabilize TCP transcription factors, but instigated weaker changes in leaf morphogenesis than wild‐type SAP11.

Overall the results suggest that phytoplasma effector SAP11 has a modular organization in which at least three domains are required for efficient CIN‐TCP destabilization in plants.
Varied clinical course of aplastic crisis in hereditary spherocytosis
Authors: Kataoka Akihiro , Doi Shoichi , Suemori Shinichiro , Nakanishi Hidekazu , Jonen Daisuke , Mori Mioko , Mizushima Yasuhiro , Wakazono Yoshihiro
Published: February 2014

This study is the first to report a familial case involving differing clinical courses of aplastic crisis triggered by parvovirus B19 in two patients with HS, although similar eosin‐5‐maleimide‐binding test and sodium dodecylsulfate–polyacrylamide gel electrophoresis results had been obtained for both. One patient had short‐term mild symptoms, whereas the other patient developed severe anemia that required blood transfusion, experienced fever for 13 days, and did not have any rash. The severity of aplastic crisis is reported to be correlated with the severity of the underlying hemolytic anemia; the present findings show that the severity of infection should also be considered as an important predictive factor of the severity of aplastic crisis.
Transverse testicular ectopia
Authors: Yıldız Abdullah , Yiğiter Murat , Oral Akgün , Bakan Vedat
Published: February 2014

Described herein are six cases of transverse testicular ectopia. All patients who underwent orchidopexy at the one pediatric surgical unit between October 2001 and January 2008 were evaluated. The medical records of all patients diagnosed with transverse testicular ectopia were evaluated retrospectively. Five patients (84%) were admitted with a symptomatic right inguinal hernia and empty scrotum on the left side. Only one child (16%) had left‐sided hernia and right non‐palpable testis (age ranged from 1 month to 3 years). Four patients (66%) were diagnosed in the operating theatre and the last two (33%) on inguinal ultrasound preoperatively. Magnetic resonance imaging was also performed in the last patient. Herniorrhaphy with fixation of the ectopic gonad to the opposite hemiscrotum through a transseptal incision was performed in all patients. Postoperative complications were not observed.
Correlation of mRNA and protein abundance in the developing maize leaf
Authors: Ponnala Lalit , Wang Yupeng , Sun Qi , van Wijk Klaas J.
Published: February 2014

To help understand regulation of maize leaf blade development, including sink‐source transitions and induction of C4 photosynthesis, we compared large‐scale quantitative proteome and transcriptomes collected at specific stages along the developmental maize leaf blade gradient. Proteome data were based on label‐free shotgun proteomics (spectral counting) and transcript data were based on RNA‐seq using the same source materials, and had been published previously (Nat Genet, 42, 2010, 1060–1067; The Plant Cell, 22, 2010, 3509–3542). Transcript and protein abundance followed near normal distributions, in contrast with several studies with other organisms. Protein observability correlated with transcript abundance following a ‘lazy step function’ similar to that in bacteria and yeast. mRNA and protein abundance showed significant positive correlations (up to 0.8) for log‐transformed length‐weighted normalized spectral abundance factor (NSAF) and reads per kilobase of exon model per million mapped reads (RPKM) and non‐weighted abundances (NadjSPC and COV) in dependence of function and development. Correlations were much weaker in the leaf ‘sink‐source’ transition zone, i.e. the zone with massive investments in leaf chloroplast biogenesis and build‐up of photosynthetic capacity. Clustering analyses of gene‐specific protein–mRNA ratios revealed co‐ordinated shifts in control points in gene expression along the leaf blade developmental gradient. The highest protein–mRNA ratio for each gene generally corresponded to leaf developmental stages in which the protein function was most important, with the exception of the 80S ribosome. Specific examples are discussed in the context of C4 photosynthesis, leaf development and sink‐source transitions. This large‐scale mRNA–protein correlation analysis in plants (maize) using label‐free spectral counting for protein quantification and RNA‐seq for mRNA abundance will provide a template for future mRNA–protein correlation studies.
Predict TKA Prosthesis Constraint Behavior Using Simulation: Validation and Applications
Authors: Gao Bo , Angibaud Laurent
Published: February 2014

Total knee arthroplasty (TKA) prostheses are semi-constrained artificial joints. A particular prosthesis design should have a level of femorotibial constraint that matches the device’s clinical indication. For example, a cruciate retaining (CR) TKA prosthesis is indicated for patients who have a fully functioning posterior cruciate ligament (PCL), while a CR-Constrained (CRC) prosthesis that compensates for PCL function by increasing sagittal conformity to offer additional anterior stability might be indicated for those who do not.
Advancements in Implantable Cardioverter Defibrillator (ICD) Device Design to Increase Patient Comfort
Authors: Flo Daniel S. , Lahm Ryan P. , Castle Michael W.
Published: February 2014

ICDs have the potential to cause physical discomfort for the patient and are typically implanted on top of the pectoral muscle and under subcutaneous tissue. High skin pressures and skin strains in the implant site, or pocket, have been theorized to be an indicator of discomfort, or in extreme cases, skin erosion. A reduction in skin pressures can be assumed to be consistent with an increase in overall patient comfort for subcutaneous implants, ref [1, 2, 3, 4, and 5]. Pocket size is governed by each physician’s implant technique and overall device shape.
Finite Element Simulations of Left Atrial Filling Following Radiofrequency Ablation
Authors: Moyer Christian B. , Norton Patrick T. , Ferguson John D. , Holmes Jeffrey W.
Published: February 2014

Atrial fibrillation (AF) is a cardiac rhythm disorder characterized by rapid, erratic muscle contraction without concordant chamber motion. Given the rising prevalence of AF and failures of pharmaceutical therapies, clinicians have increasingly used radiofrequency (RF) ablation to electrically isolate the abnormal tissue [1]. A typical ablation procedure (PVI) electrically isolates the pulmonary veins (PV) by encircling them with lesions and has a 60% success rate [2]. More aggressive procedures have been proposed to increase the success rate, including wide-area circumferential ablation (WACA), which add more lesions without considering the functional impact of additional scarring [3]. The objective of this study was to develop a finite element model of a healthy left atrium, capable of simulating passive filling during ventricular systole, and explore the functional impact of ablation by simulating various scar patterns.
Open Knee: A Pathway to Community Driven Modeling and Simulation in Joint Biomechanics
Authors: Erdemir Ahmet
Published: February 2014

Computational modeling and simulation (M&S) in biomechanics is extending its reach from research environments towards translational applications. In particular to the knee joint, finite element (FE) analysis has significant utility to understand joint and tissue function, explore pathological conditions and injury mechanisms, and investigate surgical interventions and implant performance [1]. Unfortunately, while FE models of joints, in particular of the knee, are ubiquitous in literature [1], they are not necessarily available publicly for the community to reuse and further develop. In response, Open Knee project, for FE analysis of the tibiofemoral joint, was launched [2].
Confidence Estimates due to Uncertainty in Multi-Disciplinary Computational Analysis
Authors: Dey Animesh , Tryon Robert
Published: February 2014

Simulation-based design and certification is fundamentally about making decisions with uncertainty. However, minimizing uncertainty comes at a price — more testing to better define the variability in input parameters, higher fidelity analyses at a finer scale to limit the uncertainty in the physics, etc. Variability in each input parameter does not affect the uncertainty in the system response equally. Nor does every model refinement reduce the uncertainty in the system response. This paper presents a computational methodology that estimates the sensitivity of uncertainty in input variables and the sensitivity of modeling approximations to the final output. In the current age of large multi-disciplinary virtual simulation, this is useful in determining how to minimize overall uncertainty in analytical predictions. In addition, the methodology can be used to optimize for the best use of computational and testing resources to arrive at most robust predictions.
Finite Element Modeling of a Mainstream Capnometer System for Non-Intubated Pediatric Patients Requiring Oxygen Administration
Authors: Takatori Fumihiko , Inoue Masayuki , Yamamori Shinji , Abe Seiki , Maltese Matthew R. , Nadkarni Vinay M. , Miyasaka Katsuyuki
Published: February 2014

Capnometry is the standard of care to measure the amount of carbon dioxide in the proximal airway, detect apnea, tracheal tube dislodgement, and effectiveness of ventilation during invasive mechanical ventilation in critically ill infants, children and adults [1]. Capnometry is not yet standard practice for non-invasively supported or ventilated patients, due to dead space ventilation, inspiratory gas washout, gas entrainment, and potential for rebreathing of gas. Potential capnometry use in non-intubated patients could identify impending respiratory failure, obstructed airways, and improve the safety and effectiveness of non-invasive support for infants and children [2].
Computational Framework for Determining Patient-Specific Total Knee Arthroplasty Loading
Authors: Lundberg Hannah J. , Wimmer Markus A.
Published: February 2014

The demand for total knee arthroplasty (TKA) is increasing steadily. In 2007, Kurtz et al. [1] predicted that TKA procedures would increase from 402,100 in 2003 to 3.48 million by 2030. Recent US national inpatient survey data have borne out these trends [2, 3]. Furthermore, demand is growing fastest in people younger than 65 [4] — patients who will need their implants to last the longest. The major factors limiting prosthesis longevity involve wear of the polyethylene bearing surfaces. Wear continues to be a problem at the knee; for example, advances that reduce hip implant wear such as crosslinking of polyethylene are not widely used in TKA due to fears of early material breakdown under knee loading conditions [5]. Preclinical TKA testing is performed with knee wear simulators under generic walking conditions. Efforts are ongoing by us [6] and others [7] to improve the physiological relevance of current testing standards. Nevertheless, a simulator would need to run ∼eight months continuously to simulate 20 years of walking, assuming one-million steps per year and speed of one cycle per second. As a complementary tool, computational models can test multiple conditions efficiently and ensure a faster turnaround time in the design process to eliminate inferior designs earlier. The purpose of this work is to describe a computational framework for predicting TKA loading, and ultimately implant longevity, on a patient-specific basis. The rationale is that, after developing a patient-specific computational framework, TKA designs of any material and under any patient behavior can be modulated to promote contact conditions best for implant longevity.
Blood Damage Quantification in Cardiovascular Flows Through Medical Devices Using a Novel Suspension Flow Method
Authors: Yun B. Min , Aidun Cyrus K. , Yoganathan Ajit P.
Published: February 2014

A numerical suspension flow solver is presented that can accurately quantify blood damage in cardiovascular flows. This method is capable of high spatiotemporal resolution simulations with optimal parallel computing. In addition, the method models realistic platelets for more accurate damage quantification compared to alternative methods. The numerical tool is tested on a baseline case of a St. Jude Medical bileaflet mechanical heart valve, and blood damage results are analyzed in both Lagrangian and Eulerian viewpoints.
Finite Element Analysis Model Validation to Evaluate Trabecular Metal Tibial Cones Used in Revision Total Knee Arthroplasty
Authors: Dharia Mehul A. , Stoller Alex P.
Published: February 2014

A comparative finite element analysis (FEA) model was developed to predict the relative stresses and strains in Zimmer NexGen®Trabecular Metal™ Tibial Cone components. The FEA predictions were compared to measurements obtained through physical testing. The model was validated for its ability to correctly rank the order of predicted strain in the components under applied load.
Computational Models to Predict the Structural Reliability of Aerospace Systems
Authors: Tryon Robert G. , Dey Animesh , Holmes Richard A. , Krishnan Ganapathi
Published: February 2014

Three case studies are presented in which computational-based methodologies have been used to assess structural reliability in the aerospace industry. The studies involve hot section turbine disks of a helicopter engine, fan blades of a commercial airline engine and bearings in an auxiliary power unit. In all cases, the results of the computational models were used to support the certification process for design and application changes. The statistical variation in design and usage parameters including geometry, materials, speed, temperature and other environmental factors are considered. The response surface approach was used to construct a durability performance function. This performance function is used with the first order reliability method (FORM) to determine the probability of failure and the sensitivity of the failure to the design and usage parameters. A hybrid combination of perturbation analysis and Monte Carlo simulation is used to incorporate time dependent random variables. System reliability is used to determine the system probability of failure, and the sensitivity of the system durability to the design and usage parameters.
Quantitative Assessment of the Risk of Variations During Medical Device Lifecycle
Authors: Ibrahim Ilham H. , Chassapis Constantin
Published: February 2014

The majority of medical devices are monitoring devices. Therefore, data communication and analysis are playing a crucial rule in predicting the effectiveness and reliability of a device. Device related data, patient related data and device-patient related data stored in Data Bases (DBs) are great sources for enhancing either new designs or improving already existing ones. Analyzing such data can provide researchers and device development teams with a complete justification and patterns of interest about a device’s performance, life and reliability. Data can be formulated into stochastic models based their statistical characteristics to consider the variability in data and the uncertainty about processes and procedures during early stages of the design process. This strengthens the device’s ability to function under a broader range of operating conditions. The work herein aims at targeting unwanted variations in device performance during the device development process. It employs a novel technique for variation risk management of device performance based historical process data modeling and visualization. The introduced technique is a proactive systematic procedure comprises a tool set that is being placed in the larger framework of the risk management procedure and fully utilizing data from the DBs to predict and address the risk of variations at the early stages of the design process rather than at the end of each major stage.
pELAFINT3D: A Unified Approach for Modeling Prosthetic Heart Valves
Authors: Mousel John A. , Vigmostad Sarah C. , Udaykumar H. S. , Chandran Krishnan B.
Published: February 2014

Cutting edge computational tools are an important component of the future of tasks such as surgical planning of mitral valve repair and the design and evaluation of prosthetic valves. For example, despite half a century of use, mechanical heart valves still require further research to reduce the non-physiologic nature of the flow field, which is the source of potential medical complications, of which the most serious complication is thrombus formation [1]. In fact, there is still a lack of consensus in the literature about which flow pathologies are the most damaging to blood elements [2, 3]. Much computational work has been performed examining the flow around mechanical heart valve devices [4, 5], but because the emphasis has been on correct valve motion and not fine structure detail, only the largest features have been adequately resolved and the forward flow structures are allowed to dissipate on stretched meshes such that the features may not lead to the correct fine structure state as directionality of blood flow changes during the cardiac cycle.
Finite Element Method Oriented Failure Analysis of Medical Implants: Artificial Knee
Authors: Sivarasu Sudesh , James Sam Prasanna , Mathew T. Lazar
Published: February 2014

The application of Finite Element Modelling in Medical Applications has been evolving as the field of high importance especially in the development of medical devices. The Total Knee Arthroplasty [TKA] has been in existence for over 6 decades till now. The generic artificial knee implants used in the TKA have the restriction in its range of motion with around 90 degrees. A new design allowing flexion extension range of over 120 degrees was designed with a view to facilitate partial squatting and the same is used for the analysis purpose. The new design of the artificial knee has a flexion extension range of 130 degrees. The higher flexion of the knee is obtained by use of the rotating platform knee design principle and also by adopting a multi-radii approach for the femoral component design.

The loading conditions of 10 times the body weight are considered for structural analyses of the novel knee. A maximum load of 700Kg were subjected on the knee implants. The finite element analyses of the designs were carried out based on standard biomaterial used in orthopedic implants. In this paper we have discussed the results of analyses of an artificial knee with Ti alloy. The results of the analyses were used in identifying areas of extreme stresses within the design and the spot prone for higher deformation. Based on these results slight modification on the designs was carried out. The results are also verified whether the body is within the linear deformation levels. As the results obtained were very satisfactory the models have been recommended for prototyping.
Tesla-Based Blood Pump and its Applications
Authors: Jhun Choon-Sik , Newswanger Ray , Cysyk Joshua , Lukic Branka , Weiss William , Rosenberg Gerson
Published: February 2014

A continuous flow left ventricular assist device (LVAD) that the Penn State University has developed utilizes Tesla turbomachinery technology. Tesla pumping technology patented by Nikola Tesla in the early 20th century has multiple intriguing characteristics such as simpler manufacturing process, reduced turbulent-related stress, less cavitation due to viscous flow distribution over larger surface areas, and less hemolysis by smooth transition of fluid energy. We successfully tested the 1st version of the Penn State Tesla LVAD [1, 2]. We recently tested the 2nd version of the Tesla pump; to make the pump usable in a wide range of patients, the size of the pump was significantly reduced while trying to avoid any degradation of hemodynamic and hemolytic characteristics.
How Good is Good Enough? Lessons in Musculoskeletal Model Validation With the Anybody Modeling System
Authors: Petrella Anthony , Rasmussen John , Al Munajjed Amir , Damsgaard Michael , Lund Morten , Kiis Arne
Published: February 2014

In the last two decades a steady evolution has taken place in the realm of musculoskeletal simulation, which is now taking an increasingly central role in guiding ergonomics evaluations, influencing medical device design, and informing clinical decisions. Musculoskeletal simulation holds tremendous promise to help bring safer, more innovative products to market more quickly and to drive optimized, patient-specific care. But, to effectively deliver on these challenging goals, both the software and the models created from it must meet high expectations for verification and validation so that critical choices influenced by simulation can be made with confidence. Verification is the job of the software developer, but due to the breadth of modeling applications, the task of validation falls to the user. Rigorous model validation is time consuming and often technically difficult. And so, the question arises, in the context of both verification and validation, “How good is good enough?” The goal of this paper is to offer a response to that question. The discussion will be complemented by relevant validation examples from the open literature pertaining to one commercial musculoskeletal simulation software, the AnyBody Modeling System (AMS).
Uncertainty Estimations for Particle Image Velocimetry in a Medical Device Analog (Nozzle) Model
Authors: Raben Jaime S. , Hariharan Prasanna , Robinson Ronald , Malinauskas Richard , Vlachos Pavlos P.
Published: February 2014

Particle Image Velocimetry (PIV) is currently the most widely used and well-established tool for non-invasive flow field velocity measurements, and a valuable method for validating computational fluid dynamics (CFD) models of medical devices. One of the critical steps in the CFD validation process is quantification of the experimental uncertainties. This work utilizes a new uncertainty estimation methodology developed by Charonko et al.1 for quantifying the PIV cross-correlation uncertainties. Uncertainties from experimental sources, including image magnification and acquisition timing, were propagated using Taylor series expansion for PIV data within the FDA benchmark Nozzle model2.
Modeling the Role of Oscillatory Flow and Dynamic Mechanical Conditioning on Dense Connective Tissue Formation in Mesenchymal Stem Cell Derived Heart Valve Tissue Engineering
Authors: Soares João S. , Le Trung L. , Sotiropoulos Fotis , Sacks Michael S.
Published: February 2014

Living tissue engineered heart valves (TEHV) may circumvent ongoing problems in pediatric valve replacements, offering optimum hemodynamic performance and the potential for growth, remodeling, and self-repair [1]. Although a myriad of external stimuli are available in current bioreactors (e.g. oscillatory flows, mechanical conditioning, etc.), there remain significant bioengineering challenges in determining and quantifying parameters that lead to optimal ECM development and structure for the long term goal of engineering TEHVs exhibiting tissue architecture functionality equivalent to native tissue. It has become axiomatic that in vitro mechanical conditioning promotes engineered tissue formation (Figure 1), either in organ-level bioreactors or in tissue-level bioreactors with idealized-geometry TE constructs. However, the underlying mechanisms remain largely unknown. Efforts to date have been largely empirical, and a two-pronged approach involving novel theoretical developments and close-looped designed experiments is necessary to reach a better mechanistic understanding of the cause-effect interplay between MSC proliferation and differentiation, newly synthetized ECM, and tissue formation, in response to the controllable conditions such as scaffold design, oxygen tension, nutrient availability, and mechanical environment during incubation. We thus evaluate the influence of exterior flow oscillatory shear stress and dynamic mechanical conditioning on the proliferative and synthetic behavior of MSCs by employing a novel theoretical framework for TE. We employ mixture theory to describe the evolution of the biochemical constituents of the TE construct and their intertwined biochemical reactions, evolving poroelastic models to evaluate the enhancement of nutrient transport occurring with dynamic mechanical deformations, and computational fluid dynamics (CFD) to assess the exterior flow boundary conditions developed in the flex-stretch-flow (FSF) bioreactor [4–6].
Patient-Specific Finite Element Simulations of Standard Incisional Astigmatism Surgery and a Novel Patterned Collagen Crosslinking Approach to Astigmatism Treatment
Authors: Seven Ibrahim , Dupps William J.
Published: February 2014

The cornea provides the majority of the eye’s refractive power and is the most important ocular determinant of retinal image quality. The refractive power of the cornea derives from its shape, and this shape is a function of the ocular biomaterial properties and loading forces such as the intraocular pressure (IOP). Finite element analysis has been explored as a tool for estimating the refractive outcomes of corneal interventions such as laser in-situ keratomileusis (LASIK) and photorefractive keratectomy (PRK)[1].
Nano-Bio-Cogno Model of Acoustic Patterning for Molecular Neurostimulation
Authors: Lacatus Elena , Savulescu Alexandru Florin
Published: February 2014

To define a nano-bio-cogno model able to relate acoustic patterning on crystallization of biocompatible colloids to electrolytic molecular neurostimulation, means to functionally relate the in vitro and in vivo experiments aiming to find the key towards some objectively personalized therapies.

For this interdisciplinary research, from the wide spectrum of acoustic frequencies were selected the biologically safe values for in vitro and in vivo experiments, aiming to define a possible relationships between the crystallization patterns of biocompatible colloidal electrolytes and the dynamics of neural activity under the influence of the same acoustic stimuli.
Non-Circular Configurations Increase Heart Valve Leaflet Stresses and Alter Leaflet Kinematics: A Computational Approach
Authors: Duraiswamy Nandini , Ekrami Yasamin , Weaver Jason , Retta Stephen , Wu Changfu
Published: February 2014

Transcatheter heart valve (THV) technology represents a new treatment option for many patients with severe aortic stenosis, especially those who may be ‘high risk’ candidates for valve replacement surgery. THVs are typically deployed through a small incision in either the thigh (transfemoral approach) or the chest (transapical approach). As opposed to traditional heart valve replacement surgery, THVs are deployed within the diseased valve. The metal frame pushes against the calcified leaflets and is held in place via the frame’s interaction with the native diseased valve and annular tissue. The compliant nature of the THV combined with the rigid diseased tissue has resulted often in deformed deployment of THVs clinically [1, 2].
Multi-Scale Modeling of the Heart for Closed-Loop Evaluation of Pacemaker Software
Authors: Jiang Zhihao , Mangharam Rahul
Published: February 2014

Implantable cardiac pacemakers restore normal heart rhythm by delivering external electrical pacing to the heart. The pacemaker software is life-critical as the timing of the pulses determine its ability to control the heart rate. Recalls due to software issues have been on the rise with the increasing complexity of pacing algorithms. Open-loop testing remains the primary approach to evaluate the safety of pacemaker software. While this tests how the pacemaker responds to stimulus, it cannot reveal pacemaker malfunctions which drive the heart into an unsafe state over multiple cycles. The safety and efficacy of pacemaker software should be considered in closed-loop with the physical environment of the heart. Formal Methods-based Model Checking has been an effective method for mathematically verifying all possible executions of the closed-loop system against safety properties. In this work, we used Timed automata to develop a series of heart models at different abstraction levels, which capture the timing behavior of the heart. By maintaining the Timed Simulation relation between each abstraction level, properties satisfied by the abstract model also hold in the actual system. With a Counter-Example-Guided Abstraction and Refinement (CEGAR) framework we can verify pacemaker efficiently without sacrificing accuracy.
Fracture Prediction of Cardiac Lead Medical Devices Using Bayesian Networks
Authors: Haddad Tarek , Himes Adam , Campbell Michael
Published: February 2014

A novel Bayesian Network methodology has been developed to enable the prediction of fatigue fracture of cardiac lead medical devices. The methodology integrates in-vivo measurements of device loading, patient demographics, patient activity level, in-vitro measurements of fatigue strength, and cumulative damage modeling techniques. Many plausible combinations of these variables can be simulated within a Bayesian Network framework to generate a family of fatigue fracture survival curves, enabling sensitivity analyses and the construction of confidence bounds on survival.
Challenges in Blood Flow Simulation: Numerical Methods and Image Processing Tools
Authors: Dziubek Andrea , Rusjan Edmond , Thistleton Bill
Published: February 2014

We report on recent results in modeling ocular blood flow (some parts were presented at ARVO 2013 [1]). For this simulations we used discrete exterior calculus based numerical methods. These methods aim to preserve the main features of the original analytical equations and are very suitable for curved surfaces. We will discuss the model and present the numerical methods. We will also give an overview of existing/available segmentation methods to extract the vascular tree from given retina images and our plans how to use them as a front end to our model.
Selectively grown GaAs nanodisks on Si(100) by molecular beam epitaxy
Authors: Chu Chia-Pu , Arafin Shamsul , Huang Guan , Nie Tianxiao , Wang Kang L. , Wang Yong , Zou Jin , Qasim Syed M. , BenSaleh Mohammed S.
Published: February 2014

The authors report the molecular beam epitaxial growth and the structural and optical characterizations of self-assembled/catalyst-free GaAs nanodisks on SiO2 masked Si(100) patterned substrates. Pure zincblende GaAs nanodisks with precise positioning and low defect density are demonstrated by selective area epitaxy. The influence of the growth temperature and deposition duration is investigated. Excellent morphological and structural properties are characterized by scanning electron microscopy and cross-sectional transmission electron microscopy. Defects in the epilayers are reduced by strain relaxation through facets formation and by a lateral overgrowth scheme atop the SiO2 mask which is corroborated by microRaman spectroscopy. In particular, the authors show how the material quality contributes to excellent optical properties observed by microphotoluminescence spectroscopy from 77 K to room temperature.
Characterization on pH sensing performance and structural properties of gadolinium oxide post-treated by nitrogen rapid thermal annealing
Authors: Yang Chia-Ming , Wang Chih-Yao , Lai Chao-Sung
Published: February 2014

A detail investigation on the pH sensing performance of Gd2O3 layer was proposed in this work. Electrolyte–insulator–semiconductor (EIS) structure with Gd2O3 layer deposited directly on silicon by reactive radio frequency sputtering with Gd target was chosen as the testing platform. The postdeposition rapid thermal annealing (RTA), performed at various temperatures for 1 min in N2 ambience, was first used to improve the pH sensing performance of Gd2O3. With RTA treatment at 800 °C, pH sensitivity of Gd2O3 EIS structure can be increased from 35.5 mV/pH to 55 mV/pH. This behavior can be explained by the increase of surface sites, which is supported by atomic force microscopy analysis. With RTA treatment at 700 °C and 800 °C, the drift coefficient for Gd2O3 layer was reduced to 0.03 and 1.2 mV/h, which is resulted from the densification of Gd2O3 layer supported by x-ray photoemission spectrometry. Therefore, Gd2O3 layer with RTA in N2 ambience at 700 °C or 800 °C could be a potential candidate for pH-sensitive membrane.
Structural, optical, and electrical properties of NiO-In composite films deposited by radio frequency cosputtering
Authors: Chen Sheng-Chi , Kuo Tsung-Yen , Lin Hsin-Chih , Wen Chao-Kuang , Lin Yu-Chin , Chen Cong-Da
Published: February 2014

In-doped NiO films with indium concentrations ranging from 0 to 30.3 at. % were deposited on glass substrates to investigate corresponding structural, optical, and electrical property variations. The x-ray diffraction patterns show that all films display only NiO peaks. When In atoms were added to NiO films, the NiO peaks shifted to lower angles, indicating that the lattice parameters of the films increased due to the larger In ions substituting for the smaller Ni ions. An electrical resistivity (ρ) too high to be measured occurred when the indium concentration in the NiO film was less than 15.6 at. %. The ρ value dropped significantly to 0.06 Ω·cm as the indium concentration increased to 26.9 at. %. Upon further raising the In to 30.3 at. %, the ρ value decreased further to 0.01 Ω·cm. All the In-doped NiO films showed n-type conduction. The transmittance of undoped NiO film is as high as 96%. On raising the indium concentration to 15.6, 19.9, 26.9, and 30.3 at. %, the transmittances decreased further to 68%, 62%, 57%, and 47%, respectively. Introducing higher In concentrations improved the films’ thermal stability of electrical resistivity.
Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies
Authors: Bettegowda Chetan , Sausen Mark , Leary Rebecca J. , Kinde Isaac , Wang Yuxuan , Agrawal Nishant , Bartlett Bjarne R. , Wang Hao , Luber Brandon , Alani Rhoda M. , Antonarakis Emmanuel S. , Azad Nilofer S. , Bardelli Alberto , Brem Henry , Cameron John L. , Lee Clarence C. , Fecher Leslie A. , Gallia Gary L. , Gibbs Peter , Le Dung , Giuntoli Robert L. , Goggins Michael , Hogarty Michael D. , Holdhoff Matthias , Hong Seung-Mo , Jiao Yuchen , Juhl Hartmut H. , Kim Jenny J. , Siravegna Giulia , Laheru Daniel A. , Lauricella Calogero , Lim Michael , Lipson Evan J. , Marie Suely Kazue Nagahashi , Netto George J. , Oliner Kelly S. , Olivi Alessandro , Olsson Louise , Riggins Gregory J. , Sartore-Bianchi Andrea , Schmidt Kerstin , Shih le-Ming , Oba-Shinjo Sueli Mieko , Siena Salvatore , Theodorescu Dan , Tie Jeanne , Harkins Timothy T. , Veronese Silvio , Wang Tian-Li , Weingart Jon D. , Wolfgang Christopher L. , Wood Laura D. , Xing Dongmei , Hruban Ralph H. , Wu Jian , Allen Peter J. , Schmidt C. Max , Choti Michael A. , Velculescu Victor E. , Kinzler Kenneth W. , Vogelstein Bert , Papadopoulos Nickolas , Diaz Luis A.
Published: February 2014

Circulating tumor DNA can be used in a variety of clinical and investigational settings across tumor types and stages for screening, diagnosis, and identifying mutations responsible for therapeutic response and drug resistance.
UK Biobank Data: Come and Get It
Authors: Allen Naomi E. , Sudlow Cathie , Peakman Tim , Collins Rory ,   on behalf of UK Biobank
Published: February 2014

UK Biobank invites scientists to make use of the vast (and growing) amounts of data in this open-access resource for public health research.
Boosting Metabolism by Sweetening the Gut
Authors: Eid Tore
Published: February 2014

Dietary fiber provides metabolic benefits, including body weight and glucose control, through microbiota-induced intestinal glucose production.
A Fine Line Between Healing and Fibrosis
Authors: Ghajar Cyrus M.
Published: February 2014

The liver’s microvascular endothelium lies at the crux of regeneration and fibrosis.
A Novel Ketolide, RBx 14255, with Activity against Multidrug-Resistant Streptococcus pneumoniae
Authors: Raj V. Samuel , Barman Tarani Kanta , Kalia Vandana , Purnapatre Kedar , Dube Smita , G. Ramkumar , Bhateja Pragya , Mathur Tarun , Chaira Tridib , Upadhyay Dilip J. , Surase Yogesh B. , Venkataramanan R. , Chakrabarti Anjan , Das Biswajit , Bhatnagar Pradip K.
Published: February 2014

We present here the novel ketolide RBx 14255, a semisynthetic macrolide derivative obtained by the derivatization of clarithromycin, for itsin vitroandin vivoactivities against sensitive and macrolide-resistantStreptococcus pneumoniae. RBx 14255 showed excellentin vitroactivity against macrolide-resistantS. pneumoniae, including an in-house-generated telithromycin-resistant strain (S. pneumoniae3390 NDDR). RBx 14255 also showed potent protein synthesis inhibition against telithromycin-resistantS. pneumoniae3390 NDDR. The binding affinity of RBx 14255 toward ribosomes was found to be more than that for other tested drugs. Thein vivoefficacy of RBx 14255 was determined in murine pulmonary infection induced by intranasal inoculation ofS. pneumoniaeATCC 6303 and systemic infection withS. pneumoniae3390 NDDR strains. The 50% effective dose (ED50) of RBx 14255 againstS. pneumoniaeATCC 6303 in a murine pulmonary infection model was 3.12 mg/kg of body weight. In addition, RBx 14255 resulted in 100% survival of mice with systemic infection caused by macrolide-resistantS. pneumoniae3390 NDDR at 100 mg/kg four times daily (QID) and at 50 mg/kg QID. RBx 14255 showed favorable pharmacokinetic properties that were comparable to those of telithromycin.
Pharmacokinetics and Safety of Boosted Elvitegravir in Subjects with Hepatic Impairment
Authors: Custodio Joseph M. , Rhee Martin , Shen Gong , Ling Kah Hiing J. , Kearney Brian P. , Ramanathan Srinivasan
Published: February 2014

Elvitegravir (EVG), an HIV strand transfer integrase inhibitor, is metabolized primarily via cytochrome P450 3A4 (CYP3A) and secondarily via glucuronidation. The pharmacokinetics (PK) and safety of cobicistat (COBI)-boosted EVG (EVG/co) were evaluated in subjects with impaired liver function. The enrolled subjects had stable moderate liver impairment (
n
= 10; Child-Pugh-Turcotte [CPT] class B) or were healthy controls (
n
= 10) matched for age (±5 years), gender, and body mass index (±15%). EVG/co (150/150 mg) was administered once daily for 10 days, followed by pharmacokinetic (PK) sampling. Safety was assessed throughout the study. EVG and COBI exposures were compared between the impairment and control groups, with a ≥100% increase considered clinically relevant. EVG and COBI protein binding was also measured. All enrolled subjects completed the study. The treatment-emergent adverse event (AE) incidences were comparable between the groups; all study drug-related AEs were mild. The geometric mean ratio (90% confidence interval [CI]) for EVG area under the concentration-time curve over the dosing interval (AUC
tau
) and maximum observed plasma concentration (
C
max
) were 135% (103%, 177%) and 141% (109%, 183%), respectively. The corresponding values for COBI were 99.8% (76.0%, 131%) and 86.1% (65.4%, 113%), respectively, indicating no clinically relevant change in exposure. No correlations were observed between the EVG and COBI exposures versus CPT score. The EVG- and COBI-free fractions were similar between groups. EVG and COBI do not require dose adjustment in moderate or mild liver impairment, as no clinically relevant PK changes were observed for EVG or COBI in this special population. No PK or safety data are available for EVG or COBI in subjects with severe hepatic impairment.
Oritavancin Activity against Staphylococcus aureus Causing Invasive Infections in U.S. and European Hospitals: a 5-Year International Surveillance Program
Authors: Mendes Rodrigo E. , Sader Helio S. , Flamm Robert K. , Farrell David J. , Jones Ronald N.
Published: February 2014

In this study, oritavancin had modal MIC, MIC
50
, and MIC
90
values of 0.03, 0.03, and 0.06 μg/ml, respectively, against
Staphylococcus aureus
. Similar results (MIC
50/90
, 0.03/0.06 μg/ml) were observed against methicillin-resistant and -susceptible isolates and those demonstrating multidrug-resistant (MDR) and non-MDR phenotypes. When oritavancin (MIC
50/90
, 0.06/0.12 mg/ml) was tested against
S. aureus
with elevated MIC values for daptomycin (i.e., 1 to 4 mg/ml) and vancomycin (i.e., 2 mg/ml), it showed MIC results 2-fold higher than those for the more susceptible vancomycin or daptomycin counterparts (MIC
50/90
, 0.03/0.06 mg/ml), yet it inhibited these isolates at ≤0.25 mg/ml.
Characterization of Heat-Stable (STa) Toxoids of Enterotoxigenic Escherichia coli Fused to Double Mutant Heat-Labile Toxin Peptide in Inducing Neutralizing Anti-STa Antibodies
Authors: Ruan Xiaosai , Robertson Donald C. , Nataro James P. , Clements John D. , Zhang Weiping
Published: February 2014

A long-standing challenge in developing vaccines against enterotoxigenic
Escherichia coli
(ETEC), the most common bacteria causing diarrhea in children of developing countries and travelers to these countries, is to protect against heat-stable toxin type Ib (STa or hSTa). STa and heat-labile toxin (LT) are virulence determinants in ETEC diarrhea. LT antigens are often used in vaccine development, but STa has not been included because of its poor immunogenicity and potent toxicity. Toxic STa is not safe for vaccines, but only STa possessing toxicity is believed to be able to induce neutralizing antibodies. However, recent studies demonstrated that nontoxic STa derivatives (toxoids), after being fused to an LT protein, induced neutralizing antibodies and suggested that different STa toxoids fused to an LT protein might exhibit different STa antigenic propensity. In this study, we selected 14 STa toxoids from a mini-STa toxoid library based on toxicity reduction and reactivity to anti-native STa antibodies, and genetically fused each toxoid to a monomeric double mutant LT (dmLT) peptide for 14 STa
-toxoid
-dmLT toxoid fusions. These toxoid fusions were used to immunize mice and were characterized for induction of anti-STa antibody response. The results showed that different STa toxoids (in fusions) varied greatly in anti-STa antigenicity. Among them, STa
N12S
, STa
N12T
, and STa
A14H
were the top toxoids in inducing anti-STa antibodies.
In vitro
neutralization assays indicated that antibodies induced by the 3×STa
N12S
-dmLT fusion antigen exhibited the greatest neutralizing activity against STa toxin. These results suggested 3×STa
N12S
-dmLT is a preferred fusion antigen to induce an anti-STa antibody response and provided long-awaited information for effective ETEC vaccine development.