Spatial modeling algorithms for reactions and transport in biological cells.

Biological cells rely on precise spatiotemporal coordination of biochemical reactions to control their functions. Such cell signaling networks have been a common focus for mathematical models, but they remain challenging to simulate, particularly in realistic cell geometries. Here we present Spatial Modeling Algorithms for Reactions and Transport (SMART), a software package that takes in high-level user specifications about cell signaling networks and then assembles and solves the associated mathematical systems.

Some observations on perceptions of radiation risks in the context of nuclear power plant accidents.

As highlighted by public reactions to accidents at nuclear plants in the past, such as those that occurred in Chernobyl (1986) and Fukushima (2011), and from numerous opinion surveys, there are considerable differences or gaps between how the public and radiation experts perceive the risks from radiation. Even within the community of experts, radiation risk perception differences can be present. The reasons for differences in radiation risk perceptions between the public and experts are complex and involve sociological, ethical and behavioural aspects of society.

Public perceptions of pharmacogenomic services in Ireland - Are people with chronic disease more likely to want service availability than those without? A questionnaire study.

Background: As pharmacogenomic services begin to emerge in primary care, the insight of the public is crucial for its integration into clinical practice.

Objectives: To establish perceptions of pharmacogenomics (awareness, understanding, openness to availability, perceived benefits and concerns, willingness to pay, and service setting) and investigate if they differ between those with and without chronic disease(s).

Methods: An anonymous, online questionnaire generated using Qualtrics® and circulated via social media and posters placed in eight participating community pharmacies was conducted with Irish adults.

Diarrhea prevalence in a randomized, controlled prospective trial of point-of-use water filters in homes and schools in the Dominican Republic.

Background: Lack of sustainable access to clean drinking water continues to be an issue of paramount global importance, leading to millions of preventable deaths annually. Best practices for providing sustainable access to clean drinking water, however, remain unclear. Widespread installation of low-cost, in-home, point of use water filtration systems is a promising strategy.

Radiometric Calibration of an Inexpensive LED-Based Lidar Sensor.

Radiometric calibration of laser-based, topographic lidar sensors that measure range via time of flight or phase difference is well established. However, inexpensive, short-range lidar sensors that utilize non-traditional ranging techniques, such as indirect time of flight, may report radiometric quantities that are not appropriate for existing calibration methods. One such lidar sensor is the TeraRanger Evo 60 m by Terabee, whose reported amplitude measurements do not vary smoothly with the amount of return signal power.

3D mesh processing using GAMer 2 to enable reaction-diffusion simulations in realistic cellular geometries.

Recent advances in electron microscopy have enabled the imaging of single cells in 3D at nanometer length scale resolutions. An uncharted frontier for in silico biology is the ability to simulate cellular processes using these observed geometries. Enabling such simulations requires watertight meshing of electron micrograph images into 3D volume meshes, which can then form the basis of computer simulations of such processes using numerical techniques such as the finite element method.

An Open-Source Mesh Generation Platform for Biophysical Modeling Using Realistic Cellular Geometries.

Advances in imaging methods such as electron microscopy, tomography, and other modalities are enabling high-resolution reconstructions of cellular and organelle geometries. Such advances pave the way for using these geometries for biophysical and mathematical modeling once these data can be represented as a geometric mesh, which, when carefully conditioned, enables the discretization and solution of partial differential equations. In this work, we outline the steps for a naïve user to approach the Geometry-preserving Adaptive MeshER software version 2, a mesh generation code written in C++ designed to convert structural data sets to realistic geometric meshes while preserving the underlying shapes.

Shear-Induced Nitric Oxide Production by Endothelial Cells.

We present a biochemical model of the wall shear stress-induced activation of endothelial nitric oxide synthase (eNOS) in an endothelial cell. The model includes three key mechanotransducers: mechanosensing ion channels, integrins, and G protein-coupled receptors. The reaction cascade consists of two interconnected parts.

Spawning aggregation behavior and reproductive ecology of the giant bumphead parrotfish, Bolbometopon muricatum, in a remote marine reserve.

The giant bumphead parrotfish (Bolbometopon muricatum) has experienced precipitous population declines throughout its range due to its importance as a highly-prized fishery target and cultural resource. Because of its diet, Bolbometopon may serve as a keystone species on Indo-Pacific coral reefs, yet comprehensive descriptions of its reproductive ecology do not exist. We used a variety of underwater visual census (UVC) methods to study an intact population of Bolbometopon at Wake Atoll, a remote and protected coral atoll in the west Pacific.

AAP principles concerning retail-based clinics.

The American Academy of Pediatrics views retail-based clinics (RBCs) as an inappropriate source of primary care for pediatric patients, as they fragment medical care and are detrimental to the medical home concept of longitudinal and coordinated care. This statement updates the original 2006 American Academy of Pediatrics statement on RBCs, which flatly opposed these sites as appropriate for pediatric care, discussing the shift in RBC focus and comparing attributes of RBCs with those of the pediatric medical home.

Implementation of an order set to adhere to national patient safety goals for warfarin therapy.

Background: In 2009, The Joint Commission mandated full compliance with National Patient Safety Goal (NPSG) 03.05.01 to reduce the likelihood of patient harm associated with anticoagulant therapy.

Alternative CHRNB4 3'-UTRs mediate the allelic effects of SNP rs1948 on gene expression.

Common genetic factors strongly contribute to both nicotine, the main addictive component of tobacco, and alcohol use. Several lines of evidence suggest nicotinic acetylcholine receptors as common sites of action for nicotine and alcohol. Specifically, rs1948, a single-nucleotide polymorphism (SNP) located in the CHRNB4 3'-untranslated region (UTR), has been associated to early age of initiation for both alcohol and tobacco use.

Structural mechanisms of allostery and autoinhibition in JNK family kinases.

c-Jun N-terminal (JNK) family kinases have a common peptide-docking site used by upstream activating kinases, substrates, scaffold proteins, and phosphatases, where the ensemble of bound proteins determines signaling output. Although there are many JNK structures, little is known about mechanisms of allosteric regulation between the catalytic and peptide-binding sites, and the activation loop, whose phosphorylation is required for catalytic activity. Here, we compare three structures of unliganded JNK3 bound to different peptides.

Impact of human D398N single nucleotide polymorphism on intracellular calcium response mediated by α3β4α5 nicotinic acetylcholine receptors.

The human CHRNA5 D398N polymorphism (rs16969968) causes an aspartic acid to asparagine change in the nicotinic acetylcholine receptor (nAChR) α5 subunit gene. The N398 variant of CHRNA5 is linked to increased risk for nicotine dependence. In this study, we explored the effect of the CHRNA5 D398N polymorphism on the properties of human α3β4* nicotinic acetylcholine receptors in human embryonic kidney (HEK) cells.

Extraordinary aggressive behavior from the giant coral reef fish, Bolbometopon muricatum, in a remote marine reserve.

Human impacts to terrestrial and marine communities are widespread and typically begin with the local extirpation of large-bodied animals. In the marine environment, few pristine areas relatively free of human impact remain to provide baselines of ecosystem function and goals for restoration efforts. Recent comparisons of remote and/or protected coral reefs versus impacted sites suggest remote systems are dominated by apex predators, yet in these systems the ecological role of non-predatory, large-bodied, highly vulnerable species such as the giant bumphead parrotfish (Bolbometopon muricatum) has received less attention.

Nitric oxide-dependent killing of aerobic, anaerobic and persistent Burkholderia pseudomallei.

Burkholderia pseudomallei infections are fastidious to treat with conventional antibiotic therapy, often involving a combination of drugs and long-term regimes. Bacterial genetic determinants contribute to the resistance of B. pseudomallei to many classes of antibiotics.

Discovery of potent and selective covalent inhibitors of JNK.

The mitogen-activated kinases JNK1/2/3 are key enzymes in signaling modules that transduce and integrate extracellular stimuli into coordinated cellular response. Here, we report the discovery of irreversible inhibitors of JNK1/2/3. We describe two JNK3 cocrystal structures at 2.

Prevention and management of positional skull deformities in infants.

Positional skull deformities may be present at birth or may develop during the first few months of life. Since the early 1990s, US pediatricians have seen an increase in the number of children with cranial asymmetry, particularly unilateral flattening of the occiput, likely attributable to parents following the American Academy of Pediatrics "Back to Sleep" positioning recommendations aimed at decreasing the risk of sudden infant death syndrome. Positional skull deformities are generally benign, reversible head-shape anomalies that do not require surgical intervention, as opposed to craniosynostosis, which can result in neurologic damage and progressive craniofacial distortion.

Selective inhibition of mitochondrial JNK signaling achieved using peptide mimicry of the Sab kinase interacting motif-1 (KIM1).

The c-jun N-terminal kinases (JNKs) are responsive to stress stimuli leading to activation of proapoptotic proteins and transcription. Additionally, JNK mitochondrial localization has been reported. To selectively target mitochondrial JNK signaling, we exploited JNK interaction with its mitochondrial scaffold, Sab, using small interfering RNAs (siRNAs) and a cell-permeable peptide corresponding to the KIM1 domain of Sab.

Increasing immunization coverage.

In 1977, the American Academy of Pediatrics issued a statement calling for universal immunization of all children for whom vaccines are not contraindicated. In 1995, the policy statement "Implementation of the Immunization Policy" was published by the American Academy of Pediatrics, followed in 2003 with publication of the first version of this statement, "Increasing Immunization Coverage." Since 2003, there have continued to be improvements in immunization coverage, with progress toward meeting the goals set forth in Healthy People 2010.

Synthesis, biological evaluation, X-ray structure, and pharmacokinetics of aminopyrimidine c-jun-N-terminal kinase (JNK) inhibitors.

Given the significant body of data supporting an essential role for c-jun-N-terminal kinase (JNK) in neurodegenerative disorders, we set out to develop highly selective JNK inhibitors with good cell potency and good brain penetration properties. The structure-activity relationships (SAR) around a series of aminopyrimidines were evaluated utilizing biochemical and cell-based assays to measure JNK inhibition and brain penetration in mice. Microsomal stability in three species, P450 inhibition, inhibition of generation of reactive oxygen species (ROS), and pharmacokinetics in rats were also measured.

MRI algorithm for medical necessity for auto accident injured patients.

Rationale: Magnetic resonance imaging (MRI) is often used as a diagnostic test to evaluate personal injury. However, it increases the health care cost. Therefore, it is important to study the necessity for using MRI.

Dronedarone: a new treatment for atrial fibrillation.

Dronedarone. Dronedarone is a benzofuran derivative pharmacologically related to amiodarone but without the iodine moiety. It is designed for the treatment of atrial fibrillation and atrial flutter.