scholarly journals Diffusion weighted imaging as a biomarker of retinoic acid induced myelomeningocele

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253583
Author(s):  
Nathan Maassel ◽  
James Farrelly ◽  
Daniel Coman ◽  
Mollie Freedman-Weiss ◽  
Samantha Ahle ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Retinoic Acid ◽  
Imaging Techniques ◽  
Effective Means ◽  
Cost Effective ◽  
Severe Form ◽  
Imaging Biomarker ◽  
Brain Volumes ◽  
Rat Fetuses ◽  
Average Diffusion Coefficient

Neural tube defects are a common congenital anomaly involving incomplete closure of the spinal cord. Myelomeningocele (MMC) is a severe form in which there is complete exposure of neural tissue with a lack of skin, soft tissue, or bony covering to protect the spinal cord. The all-trans retinoic acid (ATRA) induced rat model of (MMC) is a reproducible, cost-effective means of studying this disease; however, there are limited modalities to objectively quantify disease severity, or potential benefits from experimental therapies. We sought to determine the feasibility of detecting differences between MMC and wild type (WT) rat fetuses using diffusion magnetic resonance imaging techniques (MRI). Rat dams were gavage-fed ATRA to produce MMC defects in fetuses, which were surgically delivered prior to term. Average diffusion coefficient (ADC) and fractional anisotropy (FA) maps were obtained for each fetus. Brain volumes and two anatomically defined brain length measurements (D1 and D2) were significantly decreased in MMC compared to WT. Mean ADC signal was significantly increased in MMC compared to WT, but no difference was found for FA signal. In summary, ADC and brain measurements were significantly different between WT and MMC rat fetuses. ADC could be a useful complementary imaging biomarker to current histopathologic analysis of MMC models, and potentially expedite therapeutic research for this disease.

scholarly journals Unsuspected involvement of spinal cord in Alzheimer Disease

2019 ◽  
Author(s):  
Roberta Maria Lorenzi ◽  
Fulvia Palesi ◽  
Gloria Castellazzi ◽  
Paolo Vitali ◽  
Nicoletta Anzalone ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Alzheimer Disease ◽  
Sensorimotor Control ◽  
Cognitive Domain ◽  
Imaging Biomarker ◽  
Cervical Cord ◽  
Spinal Cord Atrophy ◽  
Cross Sectional ◽  
Brain Volumes

AbstractObjectiveBrain atrophy is an established biomarker for dementia, yet spinal cord involvement has not been investigated to date. As the spinal cord is relaying sensorimotor control signals from the cortex to the peripheral nervous system and viceversa, it is indeed a very interesting question to assess whether it is affected by atrophy in a disease that is known for its involvement of cognitive domains first and foremost, with motor symptoms being clinically assessed too. We therefore hypothesize that Alzheimer Disease severe atrophy can affect the spinal cord too and that spinal cord atrophy is indeed an important in vivo imaging biomarker contributing to understanding neurodegeneration associated with dementia.Methods3DT1 images of 31 Alzheimer’s disease (AD) and 35 healthy control (HC) subjects were processed to calculate volumes of brain structures and cross-sectional area (CSA) and volume (CSV) of the cervical cord (per vertebra as well as the C2-C3 pair (CSA23 and CSV23)). Correlated features (ρ>0.7) were removed, and best subset identified for patients’ classification with the Random Forest algorithm. General linear model regression was used to find significant differences between groups (p<=0.05). Linear regression was implemented to assess the explained variance of the Mini Mental State Examination (MMSE) score as dependent variable with best features as predictors.ResultsSpinal cord features were significantly reduced in AD, independently of brain volumes. Patients classification reached 76% accuracy when including CSA23 together with volumes of hippocampi, left amygdala, white and grey matter, with 74% sensitivity and 78% specificity. CSA23 alone explained 13% of MMSE variance.DiscussionOur findings reveal that C2-C3 spinal cord atrophy contributes to discriminate AD from HC, together with more established features. Results show that CSA23, calculated form the same 3DT1 scan as all other brain volumes (including right and left hippocampi), has a considerable weight in classification tasks warranting further investigations. Together with recent studies revealing that AD atrophy is spread beyond the temporal lobes, our result adds the spinal cord to a number of unsuspected regions involved in the disease. Interestingly, spinal cord atrophy explains also cognitive scores, which could significantly impact how we model sensorimotor control in degenerative diseases with a primary cognitive domain involvement. Prospective studies should be purposely designed to understand the mechanisms of atrophy and the role of the spinal cord in AD.

scholarly journals STAT3 Regulates the Pathogenesis and Bone Mesenchymal Stem Cells Transplantation of Spina Bifida Aperta Through Caspase-8

2020 ◽  
Author(s):  
mingyu Jiang ◽  
Ji-cheng Dai ◽  
Ming-ying Yin ◽  
Ming-yong Ren ◽  
Nan Wu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Retinoic Acid ◽  
Spina Bifida ◽  
Survival Rates ◽  
Cell Number ◽  
Caspase 8 ◽  
Rat Fetuses ◽  
Spina Bifida Aperta

Abstract Objective: To investigate the influence of signal transducer and activator of transcription-3 (STAT3) on spinal cord tissue grafts of rat fetuses with spina bifida aperta. In particular, we wished to determine if STAT3 would be related to the pathogenesis of spina bifida aperta (SBA) and permit increased survival of spinal cord transplants to improve therapeutic efficiency of cellular transplantation from 20-day pregnant (E20) rats. Method: Spina bifida aperta were induced with a single intragastric retinoic acid (140 mg/kg body weight) administration on E10. STAT3 and caspase-8 expression, caspase-8 positive cells by immunofluorescence on 14, 15, 16 and 17 day in spinal cord of rat fetuses with control group and spina bifida aperta group are analysed. The pregnant rats received fetal surgery and microinjection of Mesenchymal Stem Cells (MSCs) after STAT3 transfection on 16-day pregnant (E16), 17-day pregnant (E17) and 18-day pregnant (E18), P0, P1-6 and to P7-12 of cell passages as well as different injected cell number, then sacrificed on 20-day pregnant (E20) for spine sample collection. The Number of each group was not less than seven. The spinal cord samples were collected directly to detect survival rates of MSCs and caspase-8 expression. Results: The developmental change in caspase-8 expression of spina bifida aperta was notably increased to the top on E15 compared with no SBA fetuses with Retinoic Acid. STAT3 expression in SBA rat fetuses gradually decreased with embryonic development between E14 and E15, E15 dropped down to bottom. Specifically, the number of caspase-8 positive cells on E15 in spinal cord with SBA rat fetuses was the most; and from E16, the positive cells began to decrease. Compared with STAT3 non-transfection group, MSCs combined with STAT3 transfection on E18, P7-12 and medium injection cell number can statistically improve the success rate of transplantation. In addition, caspase-8 mRNA and protein levels were significantly decreased in STAT3 transfection transplantation contrast for SBA of cellular culture medium and STAT3 non-transfection transplantation. Conclusions: STAT3 may be associated with the pathogenesis of spina bifida aperta. Furthermore, MSCs transplantation after STAT3 transfection can increase survival rates and reduce apoptosis in the spinal column through caspase-8.

Parallel Computing for Tire Simulations

2011 ◽  
Vol 39 (3) ◽  
pp. 193-209 ◽  
Author(s):  
H. Surendranath ◽  
M. Dunbar
Keyword(s):  
High Performance ◽  
Effective Means ◽  
Cost Effective ◽  
Turnaround Time ◽  
Careful Consideration ◽  
Rolling Contact ◽  
Element Analysis ◽  
Parallel Solvers ◽  
Design Changes ◽  
Highly Nonlinear

Abstract Over the last few decades, finite element analysis has become an integral part of the overall tire design process. Engineers need to perform a number of different simulations to evaluate new designs and study the effect of proposed design changes. However, tires pose formidable simulation challenges due to the presence of highly nonlinear rubber compounds, embedded reinforcements, complex tread geometries, rolling contact, and large deformations. Accurate simulation requires careful consideration of these factors, resulting in the extensive turnaround time, often times prolonging the design cycle. Therefore, it is extremely critical to explore means to reduce the turnaround time while producing reliable results. Compute clusters have recently become a cost effective means to perform high performance computing (HPC). Distributed memory parallel solvers designed to take advantage of compute clusters have become increasingly popular. In this paper, we examine the use of HPC for various tire simulations and demonstrate how it can significantly reduce simulation turnaround time. Abaqus/Standard is used for routine tire simulations like footprint and steady state rolling. Abaqus/Explicit is used for transient rolling and hydroplaning simulations. The run times and scaling data corresponding to models of various sizes and complexity are presented.

Exploring the Benefits of Early Contractor Involvement (ECI) and the Mechanism for Automated 5D BIM Quantification Process in Offsite Modular Construction

2016 ◽  
Author(s):  
Tochukwu Moses ◽  
David Heesom ◽  
David Oloke ◽  
Martin Crouch
Keyword(s):  
Effective Means ◽  
Cost Effective ◽  
Modular Construction ◽  
Automated Quantification ◽  
Building Information ◽  
Project Risks ◽  
Value Add ◽  
The Uk ◽  
The Impact ◽  
Level 2

The UK Construction Industry through its Government Construction Strategy has recently been mandated to implement Level 2 Building Information Modelling (BIM) on public sector projects. This move, along with other initiatives is key to driving a requirement for 25% cost reduction (establishing the most cost-effective means) on. Other key deliverables within the strategy include reduction in overall project time, early contractor involvement, improved sustainability and enhanced product quality. Collaboration and integrated project delivery is central to the level 2 implementation strategy yet the key protocols or standards relative to cost within BIM processes is not well defined. As offsite construction becomes more prolific within the UK construction sector, this construction approach coupled with BIM, particularly 5D automated quantification process, and early contractor involvement provides significant opportunities for the sector to meet government targets. Early contractor involvement is supported by both the industry and the successive Governments as a credible means to avoid and manage project risks, encourage innovation and value add, making cost and project time predictable, and improving outcomes. The contractor is seen as an expert in construction and could be counter intuitive to exclude such valuable expertise from the pre-construction phase especially with the BIM intent of äóÖbuild it twiceäó», once virtually and once physically. In particular when offsite construction is used, the contractoräó»s construction expertise should be leveraged for the virtual build in BIM-designed projects to ensure a fully streamlined process. Building in a layer of automated costing through 5D BIM will bring about a more robust method of quantification and can help to deliver the 25% reduction in overall cost of a project. Using a literature review and a case study, this paper will look into the benefits of Early Contractor Involvement (ECI) and the impact of 5D BIM on the offsite construction process.

scholarly journals mRNA-Based Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 390
Author(s):  
Frank Kowalzik ◽  
Daniel Schreiner ◽  
Christian Jensen ◽  
Daniel Teschner ◽  
Stephan Gehring ◽  
...  
Keyword(s):  
Large Scale ◽  
New Technologies ◽  
Vaccine Development ◽  
Effective Means ◽  
Cost Effective ◽  
Clinical Applications ◽  
Cell Mediated Immunity ◽  
Healthy Individuals ◽  
Emerging Pathogens ◽  
Cell Genome

Increases in the world’s population and population density promote the spread of emerging pathogens. Vaccines are the most cost-effective means of preventing this spread. Traditional methods used to identify and produce new vaccines are not adequate, in most instances, to ensure global protection. New technologies are urgently needed to expedite large scale vaccine development. mRNA-based vaccines promise to meet this need. mRNA-based vaccines exhibit a number of potential advantages relative to conventional vaccines, namely they (1) involve neither infectious elements nor a risk of stable integration into the host cell genome; (2) generate humoral and cell-mediated immunity; (3) are well-tolerated by healthy individuals; and (4) are less expensive and produced more rapidly by processes that are readily standardized and scaled-up, improving responsiveness to large emerging outbreaks. Multiple mRNA vaccine platforms have demonstrated efficacy in preventing infectious diseases and treating several types of cancers in humans as well as animal models. This review describes the factors that contribute to maximizing the production of effective mRNA vaccine transcripts and delivery systems, and the clinical applications are discussed in detail.

scholarly journals Epidemiology of spinal cord and column tumors

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. i5-i9
Author(s):  
Joshua T Wewel ◽  
John E O’Toole
Keyword(s):  
Spinal Cord ◽  
Treatment Options ◽  
Survival Rates ◽  
Spinal Metastases ◽  
Cord Compression ◽  
Severe Form ◽  
Spinal Instability ◽  
Treatment Cascade ◽  
Tumor Pathology ◽  
Pathologic Fractures

Abstract The spine is a frequent location for metastatic disease. As local control of primary tumor pathology continues to improve, survival rates improve and, by extension, the opportunity for metastasis increases. Breast, lung, and prostate cancer are the leading contributors to spinal metastases. Spinal metastases can manifest as bone pain, pathologic fractures, spinal instability, nerve root compression, and, in its most severe form, spinal cord compression. The global extent of disease, the spinal burden, neurologic status, and life expectancy help to categorize patients as to their candidacy for treatment options. Efficient identification and workup of those with spinal metastases will expedite the treatment cascade and improve quality of life.

A method for correcting acoustic finite-difference amplitudes for elastic effects

Geophysics ◽  
2014 ◽  
Vol 79 (4) ◽  
pp. T243-T255 ◽  
Author(s):  
James W. D. Hobro ◽  
Chris H. Chapman ◽  
Johan O. A. Robertsson
Keyword(s):  
Wave Equation ◽  
Finite Difference ◽  
Effective Means ◽  
Cost Effective ◽  
P Wave ◽  
S Waves ◽  
Velocity Models ◽  
Acoustic Simulation ◽  
Wide Range ◽  
Elastic Simulation

We present a new method for correcting the amplitudes of arrivals in an acoustic finite-difference simulation for elastic effects. In this method, we selectively compute an estimate of the error incurred when the acoustic wave equation is used to approximate the behavior of the elastic wave equation. This error estimate is used to generate an effective source field in a second acoustic simulation. The result of this second simulation is then applied as a correction to the original acoustic simulation. The overall cost is approximately twice that of an acoustic simulation but substantially less than the cost of an elastic simulation. Because both simulations are acoustic, no S-waves are generated, so dispersed converted waves are avoided. We tested the characteristics of the method on a simple synthetic model designed to simulate propagation through a strong acoustic impedance contrast representative of sedimentary geology. It corrected amplitudes to high accuracy for reflected arrivals over a wide range of incidence angles. We also evaluated results from simulations on more complex models that demonstrated that the method was applicable in realistic sedimentary models containing a wide range of seismic contrasts. However, its accuracy was reduced for wide-angle reflections from very high impedance contrasts such as a shallow top-salt interface. We examined the influence of modeling at coarse grid resolutions, in which converted S-waves in the equivalent elastic simulation are dispersed. These results provide some validation for the accuracy of the method when applied using finite-difference grids designed for acoustic modeling. The method appears to offer a cost-effective means of modeling elastic amplitudes for P-wave arrivals in a useful range of velocity models. It has several potential applications in imaging and inversion.

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