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Magnetic resonance elastography (MRE) is a rapidly developing medical imaging technique that allows for quantitative assessment of the biomechanical properties of the tissue. MRE is now regarded as the most accurate noninvasive test for detecting and staging liver fibrosis. A two-dimensional (2D MRE) acquisition version is currently deployed at >2000 locations worldwide. 2D MRE allows for the evaluation of the magnitude of the complex shear modulus, also referred to as stiffness. The development of 3D vector MRE has enabled researchers to assess the biomechanical properties of small organs where wave propagation cannot be adequately analyzed with the 2D MRE imaging approach used in the liver. In 3D vector MRE, the shear waves are imaged and processed throughout a 3D volume and processed with an algorithm that accounts for wave propagation in any direction. Additionally, the motion is also imaged in x, y, and z directions at each voxel, allowing for more advanced processing to be applied. This review describes the technical principles of 3D vector MRE, surveys its clinical applications in small organs, and discusses potential clinical significance of 3D vector MRE. 3D vector MRE is a promising tool for characterizing the biomechanical properties of small organs such as the uterus, pancreas, thyroid, prostate, and salivary glands. However, its potential has not yet been fully explored. [Display omitted] • 3D Vector MRE has high clinical potential for the assessment of small organs. • 3D Vector MRE of the uterus, pancreas, thyroid, prostate, and parotid is feasible. • 3D Vector MRE provides information on the biomechanical properties of small organs. • 3D Vector MRE helps to differentiate between healthy and pathological tissue. • More research is needed to optimize the performance of 3D Vector MRE in small organs. [ABSTRACT FROM AUTHOR]

Magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) are complementary imaging techniques that detect disease based on viscoelasticity and water mobility, respectively. However, the relationship between viscoelasticity and water diffusion is still poorly understood, hindering the clinical translation of combined DWI-MRE markers. We used DWI-MRE to study 129 biomaterial samples including native and cross-linked collagen, glycosaminoglycans (GAGs) with different sulfation levels, and decellularized specimens of pancreas and liver, all with different proportions of solid tissue, or solid fractions. We developed a theoretical framework of the relationship between mechanical loss and tissue-water mobility based on two parameters, solid and fluid viscosity. These parameters revealed distinct DWI-MRE property clusters characterizing weak, moderate, and strong water-network interactions. Sparse networks interacting weakly with water, such as collagen or diluted decellularized tissue, resulted in marginal changes in water diffusion over increasing solid viscosity. In contrast, dense networks with larger solid fractions exhibited both free and hindered water diffusion depending on the polarity of the solid components. For example, polar and highly sulfated GAGs as well as native soft tissues hindered water diffusion despite relatively low solid viscosity. Our results suggest that two fundamental properties of tissue networks, solid fraction and network polarity, critically influence solid and fluid viscosity in biological tissues. Since clinical DWI and MRE are sensitive to these viscosity parameters, the framework we present here can be used to detect tissue remodeling and architectural changes in the setting of diagnostic imaging. The viscoelastic properties of biological tissues provide a wealth of information on the vital state of cells and host matrix. Combined measurement of viscoelasticity and water diffusion by medical imaging is sensitive to tissue microarchitecture. However, the relationship between viscoelasticity and water diffusion is still poorly understood, hindering full exploitation of these properties as a combined clinical biomarker. Therefore, we analyzed the parameter space accessible by diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE) and developed a theoretical framework for the relationship between water mobility and mechanical parameters in biomaterials. Our theory of solid material properties related to particle motion can be translated to clinical radiology using clinically established MRE and DWI. [Display omitted] [ABSTRACT FROM AUTHOR]

Both congestive (patients post-Fontan hepatopathy) and congenital (patients with ARPKD) disease can lead to hepatic fibrosis and portal hypertension with eventual development of splenomegaly. We investigated liver and spleen stiffness as measured by MRE between post-Fontan, ARPKD patients and controls independent of organ volume. Our study included 122 subjects (70 Fontan patients, 14 ARPKD patients, and 38 controls). The mean MRE liver and spleen stiffness values of Fontan patients and patients with ARPKD were compared to controls. Similarly, the liver and spleen volumes of the Fontan patients and patients with ARPKD were then compared to the volumes of controls. Post-Fontan and ARPKD patients, mean liver stiffness, mean liver volume as well as mean spleen stiffness and mean spleen volume were higher than mean liver stiffness, mean liver volume, mean spleen stiffness, and mean spleen volume of controls. While liver stiffness correlated to liver volume in controls, we found no correlation between stiffness and volume in either Fontan or ARPKD patients, which indicates MRE's ability to act as an independent biomarker. However, these findings are not true in the spleen, where there is significant association between volume and stiffness in patients with ARPKD, but not in Fontan patients or controls. Liver and spleen stiffness and volumes are significantly different among Fontan patients, ARPKD patients, and controls. Our findings suggest that beyond diagnosing fibrosis, MRE cut-off values could be disease-specific since not only the severity but the underlying pathology causing organ congestion or fibrosis influences MRE results. • Liver and spleen stiffness and volumes were significantly different among groups; and can be used with longitudinal disease assessments. • Liver and spleen stiffness' and volumes of patients with ARPKD and Fontan are higher than controls. • MRE cut-off values could be disease specific as not only the severity but underlying pathology causing organ congestion influences MRE results. [ABSTRACT FROM AUTHOR]

Among the large population of patients with non-alcoholic fatty liver disease (NAFLD), identifying those with fibrotic non-alcoholic steatohepatitis (Fibro-NASH) is a clinical priority, as these patients are at the highest risk of disease progression and will benefit most from pharmacologic treatment. MRI-based proton density fat fraction (MRI-PDFF) and MR elastography (MRE) can risk-stratify patients with NAFLD by assessing steatosis and fibrosis, respectively. We developed a highly specific MRI-based score to identify patients with Fibro-NASH. This analysis included derivation (n = 103) and validation (n = 244) cohorts of patients who underwent MRI, liver biopsy, transient elastography, and laboratory testing for NAFLD from 2016-2020 in 2 tertiary care centers. To identify Fibro-NASH, a formula was developed based on MRI-PDFF, MRE, and a third variable with highest balanced accuracy per logistic regression. The MRI-aspartate aminotransferase (MAST) score was created and compared to NAFLD fibrosis (NFS), Fibrosis-4 (FIB-4), and FibroScan-aspartate aminotransferase (FAST) scores. The MAST score demonstrated high performance and discrimination in the validation cohort (AUC 0.93; 95% CI 0.88-0.97). In the validation cohorts, the 90% specificity cut-off of 0.242 corresponded to a sensitivity of 75.0%, positive predictive value (PPV) of 50.0% and negative predictive value (NPV) of 96.5%, whereas the 90% sensitivity cut-off of 0.165 corresponded to a specificity of 72.2%, PPV of 29.4%, and NPV of 98.1%. Compared to NFS and FIB-4, MAST resulted in fewer patients having indeterminate scores and an overall higher AUC. Compared to FAST, MAST exhibited a higher AUC and overall better discrimination. The MAST score is an accurate, MRI-serum-based score that outperforms previous scores in non-invasively identifying patients at higher risk of Fibro-NASH. Identifying patients with non-alcoholic steatohepatitis and significant fibrosis – who need treatment and are at risk of clinical liver-related outcomes – is a clinical priority. We developed a more accurate score using MRI-based technologies and a laboratory blood test (aspartate aminotransferase) that outperforms previous non-invasive scores for the identification of patients at higher risk of liver disease progression. [Display omitted] • Patients with NASH, NAS ≥4, and F≥2 (Fibro-NASH) are at the highest risk of disease progression. • Patients with Fibro-NASH are targeted for proof-of-concept NASH trials. • MRI-PDFF and MR elastography are the most common primary and secondary endpoints in NASH trials, respectively. • To identify Fibro-NASH, the MRI-AST (MAST) score was created based on these MRI techniques. • The MAST score was proven to outperform the FIB-4, NAFLD fibrosis, and FAST scores. [ABSTRACT FROM AUTHOR]

Purpose: Posterior quadrant disconnection (PQD) is a surgical procedure for medically refractory epilepsy (MRE) involving diffuse regions of the temporo-parieto-occipital lobes. We sought to compare factors and efficacy according to PQD extent.Methods: We performed a systematic review of the literature reporting the use of PQD since 2004. We analyzed various characteristics of pooled cases, including the role of preoperative studies in patient selection, intraoperative techniques, and outcomes.Results: Our review of 137 patients from nine studies revealed 66% undergoing total PQD and 34% undergoing partial PQD. Interictal electroencephalography (EEG) findings were predominantly characterized as lateralized for total PQD (56%) and localized within the ipsilateral posterior quadrant in patients undergoing partial PQD (53%). Metabolic functional studies [positron emission tomography (PET) or ictal single-photon emission computed tomography (SPECT)] played a role in surgical decision-making in 42% of patients who underwent total PQD. Wada and/or functional magnetic resonance imaging (fMRI) was more often utilized for partial PQD (22%) than total PQD (3%) as was intracranial electroencephalography (icEEG) (30% versus 13%, respectively). Overall, 75% of total PQD patients achieved seizure freedom [defined as Engel I or International League Against Epilepsy (ILAE) Class 1 outcome] in comparison to 63% of partial PQD patients (p = .078). New visual field deficits were seen in 12% and new or worsened hemiparesis in 6%. For patients in either cohort, concordance of interictal and ictal EEG findings was found to be predictive of seizure freedom (p = .048).Conclusion: Both total and partial PQD represent effective alternatives for managing patients with MRE whose seizure onset zone (SOZ) involves a diffuse region within the posterior quadrant. While PET and/or SPECT frequently aided in the decision to proceed with total PQD, patients who underwent a tailored, partial multilobar resection were more likely to undergo Wada and/or fMRI testing as well as stage I icEEG studies. [ABSTRACT FROM AUTHOR]

The pulse force generated by the propeller excites the hull through the propulsion shafting system, which is the primary source of vibration and noise of ships. In order to control the transmission of longitudinal vibration of ship shafting, a multimodal dynamic vibration absorber (MDVA) with broadband vibration control performance is proposed. A magnetorheological elastomer (MRE) was prepared and used as an elastic element to construct a semi-active dynamic vibration absorber (SDVA), designed spiral flexible springs and embedded SDVA into the proposed MDVA. An equivalent propeller propulsion shaft system model was established, and its first three longitudinal vibrations were controlled based on the MDVA. Furthermore, the stiffness and damping of the MDVA were optimized by fixed point theory. A design scheme for the MDVA considering the changes in oil film stiffness of thrust bearings under different propeller speed conditions was proposed. The results indicate that the MDVA has excellent vibration transmission control performance at the first three natural frequencies. The proposed MDVA also has a broader frequency band for controlling vibration near first-order resonance than the traditional single degree of freedom DVA, which has excellent vibration control performance under variable speed conditions. [ABSTRACT FROM AUTHOR]

The US military Meal, Ready-to-Eat food ration is approved as a nutritionally adequate sole source of nutrition for ≤21 days. However, the ration continuously evolves, requiring periodic reassessment of its influence on nutritional status and health. To determine the effects of consuming the US Armed Services Meal, Ready-to-Eat ration for 21 days, relative to usual diets, on nutrient intake, and indicators of nutritional status and cardiometabolic health. Parallel-arm, randomized, controlled trial, secondary analysis. Sixty healthy, weight stable, free-living adults from the Natick, MA, area participated between June 2015 and March 2017. Participants were randomized to consume their usual diet for 31days (CON), or a strictly controlled Meal, Ready-to-Eat-only diet for 21 days followed by their usual diet for 10 days (MRE). Nutrient intake (absolute and adjusted) throughout the study period, and indicators of nutrition status (vitamins B, D, folate, homocysteine, iron, magnesium, and zinc) and cardiometabolic health (glucose, insulin, and blood lipid levels) before (Day 0), during (Day 10 through Day 21), and after (Day 31) the intervention period. Between-group differences over time were assessed using marginal models. Models for nutritional status and cardiometabolic health indicators were adjusted for age, initial body mass index, and baseline value of the dependent variable. Energy-adjusted fiber; polyunsaturated fatty acids; vitamins A, thiamin, riboflavin, B-6, C, D, and E; and magnesium and zinc intakes all increased in MRE during the intervention and were higher compared with CON (P <0.05), whereas relative protein intake decreased and was lower (P <0.05). Serum triglyceride concentrations averaged 19% (95% CI 0% to 41%) higher in MRE relative to CON during Days 10 to 31 (P =0.05). No statistically significant effects of diet on any other nutritional status or cardiometabolic health indicators were observed. Findings demonstrate that a Meal, Ready-to-Eat ration diet can provide a more micronutrient-dense diet than usual dietary intake aiding in maintenance of nutritional status over 21 days. [ABSTRACT FROM AUTHOR]

This study examines the concept of an axisymmetric actuator based on the magnetorheological membrane, electromagnet, and permanent magnet. The construction of the actuator enables its application in a wide range of practical devices like pumping, loudspeakers, or varying stiffness buttons. This work will highlight its working principle, especially the influence of permanent magnets. Furthermore, the model of devices will be defined based on the Hammerstein model. To show the properties of the actuator and to perform the model identification, several experiments were carried out taking into account static and dynamic working conditions. • A new construction of magnetorheological axisymmetric actuator with permanent magnet. • Proposition of Hammerstein model for actuator. • The identification procedure taking into account Hammerstein model with slow and fast dynamics. • Validation of actuator in experimental tests. [Display omitted] [ABSTRACT FROM AUTHOR]

Fibrotic strictures occur in 30% of patients with Crohn's disease (CD). However, there are no therapeutic agents that prevent or reverse fibrotic strictures. Strictures are treated by endoscopic dilatation procedures and surgical procedures, but there are high rates of recurrence. Two antifibrotic agents (nintedanib and pirfenidone) recently were approved for the treatment of idiopathic pulmonary fibrosis and inhibitors of Rho-associated protein kinases 1 and 2 reversed fibrosis in mice with chronic intestinal inflammation. Cross-sectional imaging techniques, such as magnetic resonance (MR) enterography, computed tomography enterography, and bowel ultrasound, are used to assess small-bowel and CD-related complications, including strictures. It is important to be able to determine the degree of inflammation and fibrosis in strictures to select the best therapy; this can be a challenge because inflammation and fibrosis co-exist to varying degrees in a damaged bowel segment. Delayed gadolinium enhancement, magnetization transfer MR imaging, and ultrasound elastography seem to be promising tools for assessing fibrosis in patients with CD. We review noninvasive techniques for fibrosis assessment, including analyses of genetic, epigenetic, and protein markers. We discuss the potential of imaging techniques such as diffusion-weighted and magnetization transfer MR imaging, strain elastography, shear-wave imaging, and positron emission tomography to guide therapeutic decisions for patients with stricturing CD. [ABSTRACT FROM AUTHOR]

In order to simulate hydrogen charging and discharging cycles of mechanically loaded structures, an analytical solution for the differential equation of trapping kinetics is proposed, as a generalization of the Oriani's equilibrium relationship. This solution has been implemented in the Abaqus finite element software, and validated by comparison with the one-dimensional kinetic MRE Hydrogen Isotope Inventory Processes Code (HIIPC). Last, the results of an application on a 3D structure are presented. [ABSTRACT FROM AUTHOR]

Summary Non-alcoholic fatty liver disease (NAFLD) is a major public health problem afflicting approximately one billion individuals worldwide. Liver biopsy is considered the gold standard for assessment of liver disease severity in patients with NAFLD. However, it is invasive, has high inter-observer variability, and is associated with adverse effects, including pain, infection and, albeit rarely, death. It is also impractical because of the large number of individuals who have NAFLD. Therefore, tools to non-invasively assess disease severity in NAFLD are urgently needed. Over the last two decades, tremendous advances have been made in the assessment of NAFLD by non-invasive imaging. In this review, we will discuss the different non-invasive imaging modalities available to quantify liver fat and liver fibrosis. We will also discuss the limitations of current modalities to detect the progressive form for NAFLD, termed non-alcoholic steatohepatitis. Finally, we will discuss the comparative efficacy of various imaging-based elastographic modalities for detection of advanced fibrosis or cirrhosis, as well as their diagnostic characteristics. [ABSTRACT FROM AUTHOR]

Pleurotus ostreatus laccase gene poxc is transcriptionally induced by copper, and several putative MREs have been found and confirmed in its promoter region. However, the related transcription factors mediating copper response via MREs have not been reported. To isolate MRE binding proteins, we carried out yeast one-hybrid screens. Reporter genes containing two trimers of the cMRE2 and cMRE3 element were prepared and introduced into a yeast strain. The yeast was transformed with library cDNA that represents RNA isolated from CuSO 4 -treated fungi of P. ostreatus . From the screen of yeast transformants, we isolated ltf4 which encoded protein with HTH DNA binding domain. Electrophoretic mobility shift assay suggested direct and specific interaction of ltf4 with the MRE2 of poxc . Quantitative RT-PCR showed that the transcription of ltf4 was significantly up-regulated after the copper addition, and the expression trend was consistent with the poxc after copper introduction. The results indicated that ltf4 could interact with cMRE2 and thus participated in the regulation of copper mediated poxc transcription in P. ostreatus . [ABSTRACT FROM AUTHOR]

The noninvasive imaging technique of magnetic resonance elastography (MRE) was used to estimate the power law behavior of the viscoelastic properties of the human brain in vivo . The mechanical properties for four volunteers are investigated using shear waves induced over a frequency range of 10–50 Hz to produce a displacement field measured by magnetic resonance motion-encoding gradients. The average storage modulus ( μ R ) reconstructed with non-linear inversion (NLI) increased from approximately 0.95 to 2.58 kPa over the 10–50 Hz span; the average loss modulus ( μ I ) also increased from 0.29 to 1.25 kPa over the range. These increases were modeled by independent power law (PL) relations for μ R and μ I returning whole brain, group mean exponent values of 0.88 and 1.07 respectively. Investigation of these exponents also showed distinctly different behavior in the region of the cerebral falx compared to other brain structures. [ABSTRACT FROM AUTHOR]

Background Accurate diagnosis of Crohn's disease or ulcerative colitis is essential for surgical planning. This study compared the accuracy, safety, and utility of small bowel follow-through (SBFT) and magnetic resonance enterography (MRE) for detecting small bowel (SB) involvement preoperatively. Methods A retrospective review of children who underwent colectomy for inflammatory bowel disease (2000–2014) was performed. Preoperative SBFT and MRE were independently reviewed by two radiologists blinded to clinical data. Gold standard for diagnosis was surgical pathology. Results 68 patients (36 female) were included. 45 patients had SBFT prior to colectomy, 17 patients had MRE, and 6 both. Interrater reliability for radiologic interpretation was 90% (SBFT) and 91% (MRE). Mean study durations were 190 min (SBFT) and 59 min (MRE). Median effective dose for SBFT was 1.5 mSv, while MRE involved no ionizing radiation. Specificities for diagnosing SB involvement were 87.5% (SBFT) and 94% (MRE). 54 patients underwent subtotal colectomy and ileostomy, 12 restorative proctocolectomy, and 2 colectomy with ileorectal anastomosis. Preoperative imaging correlated with surgical pathology in 83% (SBFT) and 90% (MRE). Conclusion MRE is at least as effective as SBFT for assessing SB disease in children with colitis prior to colectomy. MRE requires less time and does not expose children to ionizing radiation. Retrospective Case Series, Level 4 Evidence. [ABSTRACT FROM AUTHOR]

Purpose To determine if tumor stiffness by MR Elastography (MRE) is associated with hepatocellular carcinoma (HCC) pathologic features. Material and methods A retrospective review was undertaken of all patients with pathologically confirmed HCC who underwent MRE prior to loco-regional therapy, surgical resection or transplant between 1/1/2007 to 12/31/2015. An independent observer measured tumor stiffness (kilopascals, kPa) by drawing regions of interest (ROI) covering the HCC and in the case of HCCs with non-enhancing/necrotic components, only the solid portion was included in the ROI. HCC tumor grade (WHO criteria), vascular invasion and tumor encapsulation were assessed from retrievable pathology specimens by an expert hepatobiliary pathologist. Tumor stiffness was compared by tumor grade, size, presence of capsule and vascular invasion using Student's t -test (or Exact Mann-Whitney test). Results 21 patients were identified who had pathologically confirmed HCCs and tumor MRE data. 17 patients (81.0%) had underlying chronic liver disease. The mean ± SD tumor size (cm) was 5.3 ± 3.9 cm. The mean ± SD tumor stiffness was 5.9 ± 1.4 kPa. Tumors were graded as well differentiated (N = 2), moderately differentiated (N = 11) and poorly differentiated (N = 8). There was a trend toward increased tumor stiffness in well/moderately differentiated HCCs (6.5 ± 1.2 kPa; N = 13) compared to poorly differentiated HCCs (4.9 ± 1.2 kPa; N = 8) (p < 0.01). There was no significant correlation between tumor stiffness and liver stiffness or tumor size. There was no significant difference in tumor stiffness by presence or etiology of chronic liver disease, vascular invasion or tumor encapsulation. Conclusion Preliminary data suggest that tumor stiffness by MRE may be able to differentiate HCC tumor grade. [ABSTRACT FROM AUTHOR]

Purpose To determine interobserver agreement (IOA) and accuracy of conventional MR enterography (MRE), qualitative diffusion, and apparent diffusion coefficient (ADC) values for detecting clinically active inflammation. Methods MREs in 57 consecutive children with suspected inflammatory bowel disease were retrospectively reviewed. Results Substantial IOA for conventional MRE (kappa=0.65) and qualitative diffusion (kappa=0.64), but fair to good IOA for ADC, (intra-class coefficient=0.63) were seen. Conventional MRE detected active clinical inflammation well (area under curve [AUC] 0.725), while qualitative diffusion and ADC did not perform well (AUC=0.572 and 0.461, respectively). Conclusion DWI can be helpful in diagnosing inflammatory bowel disease but does not perform well in identifying those with active inflammation. [ABSTRACT FROM AUTHOR]

This paper presents the vibration reduction of powertrain during transient stage by using magneto rheological elastomer (MRE) based adaptive tuned vibration absorber (ATVA). Torsional vibration of power train is represented by a simplified lumped mass multi degree of freedom system to verify the ATVA effectiveness. The equation of motion of the model is developed and simulated in the MATLAB to calculate the vibration characteristics such as natural frequency, damped frequency, mode shape and damping ratio of the power train system. The expressions of the storage modulus and loss factor of the MRE are generated as a function of magnetic field which was obtained from experimental data of MRE available in the literature. The responses of the powertrain system without and with ATVA were compared to verify the effectiveness of the ATVA. [ABSTRACT FROM AUTHOR]

In this work the static behavior of magnetorheological elastomer (MRE) sandwich beams is studied in flexion with transverse shear. The beam is formed by two aluminum skins bonded to a core of elastomeric silicone oil and loaded with iron particles at 30%. The rigidity of the beam is given by the addition of a usual stiffness matrix of two aluminum skins and an MRE complex stiffness matrix. The latter is a function of the magnetorheological properties of the MRE. The results show the influence of MRE adaptive stiffness and the loss factor in the static behavior of the sandwich studied. The structure proposed can be directly applied to civil engineering, for example, building foundations, mechanical engineering and aircraft wings. [ABSTRACT FROM AUTHOR]

Synucleinopathies are multifactorial neurodegenerative disorders marked by the presence of intracellular deposits of α-synuclein (α-syn) protein. Although significant progress has been made in understanding the pathogenesis of synucleinopathies, diagnosis largely relies on the clinical symptoms and histopathological analyses. A major challenge is the lack of diagnostic tests for identifying disease biomarkers. As aggregation of α-syn is one of the key indicators of disease, this protein is of interest as a target biomarker for the development of diagnostic platforms. In this review, we outline emerging evidence that highlights the importance of α-syn as a reliable biomarker for synucleinopathies. We present a comprehensive overview of the underlying principle of different methods available for the detection of α-syn which either use molecular recognition elements (MREs) to obtain specificity, or direct detection where specificity is obtained by using sensor components. Finally, the review provides a critical outlook on the current trends and challenges in α-syn based disease diagnosis and makes recommendations for the steps needed to achieve full diagnostic potential of the available methods. [Display omitted] • Challenges in identification and diagnosis of synucleinopathies. • Different analytical methods and sensors for the detection of α-syn conformers. • Overview on the sensitivity and specificity of methods available for the detection of α-syn. • Need for new molecular recognition elements for the detection of specific α-syn conformers. [ABSTRACT FROM AUTHOR]

Mechanical properties of brain tissue are very complex and vary with the species, region, method, and dynamic range, and between in vivo and ex vivo measurements. To reconcile this variability, we investigated in vivo and ex vivo stiffness properties of two distinct regions in the human and mouse brain - the hippocampus (HP) and the corpus callosum (CC) - using different methods. Under quasi-static conditions, we examined ex vivo murine HP and CC by atomic force microscopy (AFM). Between 16 and 40Hz, we investigated the in vivo brains of healthy volunteers by magnetic resonance elastography (MRE) in a 3-T clinical scanner. At high-frequency stimulation between 1000 and 1400Hz, we investigated the murine HP and CC ex vivo and in vivo with MRE in a 7-T preclinical system. HP and CC showed pronounced stiffness dispersion, as reflected by a factor of 32–36 increase in shear modulus from AFM to low-frequency human MRE and a 25-fold higher shear wave velocity in murine MRE than in human MRE. At low frequencies, HP was softer than CC, in both ex vivo mouse specimens (p < 0.05) and in vivo human brains (p < 0.01) while, at high frequencies, CC was softer than HP under in vivo (p < 0.01) and ex vivo (p < 0.05) conditions. The standard linear solid model comprising three elements reproduced the observed HP and CC stiffness dispersions, while other two- and three-element models failed. Our results indicate a remarkable consistency of brain stiffness across species, ex vivo and in vivo states, and different measurement techniques when marked viscoelastic dispersion properties combining equilibrium and non-equilibrium mechanical elements are considered. [ABSTRACT FROM AUTHOR]

This paper is devoted to developing a comprehensive size-dependent modeling for dynamic and stability analysis of a sandwich micro-shell with magnetorheological elastomer (MRE) core, subjected to a moving fluid flow. The mathematical formulation of this model is conducted on the basis of Donnell's shell theory and modified first strain gradient theory (MFSGT). Additionally, perturbation pressure of the fluid flow is considered to model and add the effect of the existing fluid to the governing fluid–solid interaction (FSI) equations. After mathematical modeling, the obtained governing motion equations are solved analytically to attain the dynamic characteristics of the system namely imaginary and real parts of eigenvalues, frequencies and loss factors of the system. Verification study is implemented and thereafter the exact influences of the involved parameters such as length scale parameter, circumferential wave number, moving flow velocity, applied magnetic intensity to the smart core and MRE core thickness on the dynamic and stability response of the system are examined and discussed in detail for first three modes. The results show an excellent and considerable role of the MRE core properties on dynamic and stability control of the system. This effect could be detected in forms of diminishing some possible instabilities of various modes or expanding the stable region of the system. It is hopeful that, the analysis and acquired results may provide a data bank; helpful for increasing the knowledge about MRE-based sandwich structures and designing more adaptable and efficient systems benefiting from advanced and smart materials. • Comprehensive modeling is presented for dynamics and stability analysis of a fluid-conveying sandwich shell with MRE core. • Perturbation pressure of the fluid flow is considered to add the existing fluid effect to the governing FSI equations. • MFSGT, Dannell's shell theory and non-steady Bernoulli equation are employed. • The effects of MRE core's intrinsic characteristics on the vibration and stability behavior of the system are investigated. • Substantial influence of the MRE smart core on stability and dynamics response of the system is revealed. • Stability improvement appears in forms of diminishing some possible instabilities or expanding the stable region. [ABSTRACT FROM AUTHOR]

The Marine Radiocarbon Reservoir Effect (MRE) is a 14 C age offset between contemporaneous marine- and terrestrially-derived carbon. In Northern Hemisphere surface waters it is of the order of 400 years but temporal and spatial deviations, known as ΔR, occur. This study provides a comprehensive dataset of 21 ΔR and MRE values for the east coast of Scotland and 21 recalculated values for the west coast of Scotland and Ireland, for the period c. 3500 BC to 1450 AD. They are presented as mean, site-specific ΔR and MRE values, together with their associated uncertainties, calculated as standard errors for predicted values. The ΔR values range from −320 ± 35 to +150 ± 28 14 C years and show no spatial or temporal trends. The MRE values range from 59 ± 40 to 531 ± 26, show an almost identical distribution pattern to the ΔR values and again show no spatial or temporal trends. Results show that ΔR values calculated for a single site using statistically indistinguishable groups of terrestrial and marine radiocarbon age measurements can produce variability of up to 225 14 C years. ΔR is an important factor in the accurate calibration of samples containing marine-derived carbon for archaeological interpretation but is often also used as an indicator of changes in 14 C specific activity of the oceans, and therefore a proxy for changes in ocean circulation and/or climate. Using the methods outlined in this paper, it is apparent that ΔR values for the northern part of the British Isles have been relatively stable, within our ability to quantify non-random variation in the data. The fact that significant climatic shifts have been recorded during this time, yet these are not visible in the ΔR data, presents a cautionary tale regarding the use of ΔR to infer large-scale oceanographic or climatic changes. Upon the exclusion of 5 outliers from the 42 values, the remaining ΔR values are statistically indistinguishable from one another and range from −142 ± 61 to +40 ± 47 14 C years. 34 of these values are from Scottish archaeological sites and can be combined to produce a mean value for Scotland of −47 ± 52 14 C years for the period 3500 BC to 1450 AD, to be used only in the absence of site- and period-specific data. [ABSTRACT FROM AUTHOR]

Magnetic resonance elastography (MRE) of the liver is a novel noninvasive clinical diagnostic tool to stage fibrosis based on measured stiffness. The purpose of this study is to design, evaluate and validate a rapid MRE acquisition technique for noninvasively quantitating liver stiffness which reduces by half the scan time, thereby decreasing image registration errors between four MRE phase offsets. In vivo liver MRE was performed on 16 healthy volunteers and 14 patients with biopsy-proven liver fibrosis using the standard clinical gradient recalled echo (GRE) MRE sequence (MREs) and a developed rapid GRE MRE sequence (MREr) to obtain the mean stiffness in an axial slice. The mean stiffness values obtained from the entire group using MREs and MREr were 2.72±0.85 kPa and 2.7±0.85 kPa, respectively, representing an insignificant difference. A linear correlation of R2 =0.99 was determined between stiffness values obtained using MREs and MREr. Therefore, we can conclude that MREr can replace MREs, which reduces the scan time to half of that of the current standard acquisition (MREs), which will facilitate MRE imaging in patients with inability to hold their breath for long periods. [ABSTRACT FROM AUTHOR]

Compressibility of biological tissues such as brain parenchyma is related to its poroelastic nature characterized by the geometry and pressure of vasculature and interconnected fluid-filled spaces. Thus, cerebral volumetric strain may be sensitive to intracranial pressure which can be altered under physiological conditions. So far volumetric strain has attained little attention in studies of the mechanical behavior of the brain. This paper reports a study of measuring the in vivo cerebral volumetric strain induced by the Valsalva maneuver (VM) where forced expiration against a closed glottis leads to a transient increase in the intracranial pressure. For this purpose we applied three-dimensional magnetic resonance imaging equipped with a patient-controlled acquisition system to five healthy volunteers. With each volunteer, three experiments were performed: one with VM and two in resting state. i.e. normal ventilation, which were conducted before and after VM. The VM data were registered to reference data by morphology based non-rigid deformation, yielding 3D maps of total displacements and volumetric strain. On average, VM induced volumetric strain correlated to whole-brain dilatation of - 3.14 ± 0.87% and - 2.80 ± 0.71% compared to the reference states before and after VM, respectively. These values were well reproduced by repetitive experiments during the same scan as well as by repeated measurements in one volunteer on different days. Combined with literature data of intracranial pressure changes, our volumetric strain values can be used to elucidate the static compression modulus of the in vivo human brain. These results add knowledge to the understanding of the brain's biomechanical properties under physiological conditions. [ABSTRACT FROM AUTHOR]

Magnetorheological elastomers (MRE) are a type of smart materials which responds to an externally applied magnetic field which results in enhanced mechanical properties. MRE consists of a non-magnetic matrix material like rubber and a ferromagnetic ingredient. The size of the particle ingredient plays an important role in the property enhancement of the MRE. In the current work, MRE samples were prepared using Room temperature vulcanising Silicone as matrix material and 2 different samples of carbonyl iron powder (3.15 μm and 6.25 μm diameters) were used as particle ingredients. Microstructure of the sample were studied under Confocal microscope, which showed the smaller diameter powders results in more agglomeration even though the distribution of powders in the matrix were fairly uniform. A test set up was made to conduct dynamic tests to investigate the influence of particle size on the dynamic performance of the prepared MRE samples. Test results in these experiments showed that smaller diameter particle ingredients results in better MR effect. [ABSTRACT FROM AUTHOR]

Cellular zinc influx and efflux are maintained by two major transporter families, the ZIP (SLC39A) and ZnT (SLC30A or CDF) molecules. The functions of one molecule in this class, ZIP11/SLC39A11, remain unclear. Bioinformatics analysis of the distribution and evolutionary relationships of different ZIP members in eukaryotes and prokaryotes indicated that Zip11, the sole member of gufA subfamily, is an ancient ZIP family member that might have originated in early eukaryotic ancestors. Murine Zip11 mRNA is abundantly expressed in testes and the digestive system including stomach, ileum and cecum. Analysis of cellular zinc content, metallothionein levels, and cell viability under high or low zinc conditions in cells transfected with a murine Zip11 expression plasmid, suggest that Zip11 is a zinc importer. Further, cellular zinc concentrations and metallothionein levels decreased when Zip11 was knocked down. In mice supplemented with zinc, both mRNA and protein levels of Zip11 were slightly up-regulated in several tissues. The metal response element sequences (MREs) upstream of the first exon of Zip11 responded to elevated extracellular zinc concentrations, as assessed by luciferase reporter assays. Mutagenic analysis showed that several of the MREs could regulate Zip11 promoter activity, and metal-responsive transcription factor-1 (MTF-1) was shown to be involved in this process. Collectively, these data suggest that Zip11 has unique protein sequence and structure features, it functions as a cellular zinc transporter, and its expression is at least partially regulated by zinc via hMTF-1 binding to MREs of the Zip11 promoter. [ABSTRACT FROM AUTHOR]

Characterization of the dynamic mechanical behavior of brain tissue is essential for understanding and simulating the mechanisms of traumatic brain injury (TBI). Changes in mechanical properties may also reflect changes in the brain due to aging or disease. In this study, we used magnetic resonance elastography (MRE) to measure the viscoelastic properties of ferret brain tissue in vivo. Three- dimensional (3D) displacement fields were acquired during wave propagation in the brain induced by harmonic excitation of the skull at 400 Hz, 600 Hz and 800 Hz. Shear waves with wavelengths in the order of millimeters were clearly visible in the displacement field, in strain fields, and in the curl of displacement field (which contains no contributions from longitudinal waves). Viscoelastic parameters (storage and loss moduli) governing dynamic shear deformation were estimated in gray and white matter for these excitation frequencies. To characterize the reproducibility of measurements, two ferrets were studied on three different dates each. Estimated viscoelastic properties of white matter in the ferret brain were generally similar to those of gray matter and consistent between animals and scan dates. In both tissue types G' increased from approximately 3 kPa at 400 Hz to 7 kPa at 800 Hz and G" increased from approximately 1 kPa at 400 Hz to 2 kPa at 800 Hz. These measurements of shear wave propagation in the ferret brain can be used to both parameterize and validate finite element models of brain biomechanics. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study is to characterize the muscle architecture of children and adults using magnetic resonance elastography and ultrasound techniques. Five children (8–12yr) and seven adults (24–58yr) underwent both tests on the vastus medialis muscle at relaxed and contracted (10% and 20% of MVC) states. Longitudinal ultrasonic images were performed in the same area as the phase image showing the shear wave’s propagation. Two geometrical parameters were defined: the wave angle (α _MRE) corresponding to the shear wave propagation and the fascicule angle (α _US) tracking the path of fascicles. Moreover, shear modulus was measured at different localizations within the muscle and in the subcutaneous adipose tissue. The association of both techniques demonstrates that the shear wave propagation follows the muscle fascicles path, reflecting the internal muscle architecture. At rest, ultrasound images revealed waves propagating parallel to the children fascicle while adults showed oblique waves corresponding to already oriented (α _US=15.4±2.54°) muscle fascicles. In contraction, the waves’ propagation were in an oblique direction for children (α _US_10%MVC=10.6±2.27°, α _US_20%MVC=10.2±2.29°) as well as adults (α _US_10%MVC=15.4±2.54°, α _US_20%MVC=17.2±2.44°). A stiffness variation (1kPa) was found between the upper and lower parts of the adult VM muscle and a lower stiffness (1.85±0.17kPa) was measured in the subcutaneous adipose tissue. This study demonstrates the feasibility of the MRE technique to provide geometrical insights from the children and adults muscles and to characterize different physiological media. [ABSTRACT FROM AUTHOR]

Abstract: Metallothioneins (MT) are low-molecular weight, cysteine-rich metal-binding proteins. MT play a role in the homeostasis of essential metals such as zinc (Zn) and copper (Cu), detoxification of toxic metals such as cadmium (Cd) and protection against oxidative stress. In this study, we examined the expression of MT in HaCaT and C6 cells as a strategy to enhance protection against Cd-mediated toxicity. At basal level, HaCaT cells showed higher MT level than C6 cells which could explain the resistance of HaCaT cells. Western blot showed that C6 cells treated with 20μmol/L Cd for 24h did not express any MT. MT were initially expressed in the cytoplasmic or periplasmic compartment and were then translocated in the nucleus after 24h treatment by Cd both in HaCaT and C6 cells. In addition, the cell treatment with Cd was followed by an increase in the cellular zinc level but the electrophoretic mobility shift assay (EMSA) experiment did not show any translocation of metal-responsive transcription factor-1 (MTF-1) to the nucleus of HaCaT cells. These absence of translocation could be due to the presence of MT in these cells at the basal state. The translocation study in HaCaT cells suggested that the MT translocation in the nucleus was greater than observed in C6 cells. The latter observation could explain HaCaT cells resistance to Cd concentrations up to 50μmol/L. Our results suggested that the C6 cell sensitivity was correlated with the decrease in MT level at 20μmol/L Cd occurring after the transcription of MT gene. [Copyright &y& Elsevier]

Abstract: Advances in imaging technologies such as magnetic resonance elastography (MRE) have allowed researchers to gain insights into muscle function in vivo. MRE has been used to examine healthy and diseased muscle by calculating shear modulus. However, additional information can be measured from visualizing a mechanical wave as it passes through a tissue. One such measurable quantity is wave attenuation. The purpose of this study was to determine if a simple measure of wave attenuation could be used to distinguish between healthy and diseased muscle. Twenty seven subjects (14 healthy controls, 7 hyperthyroid myopathy patients, 6 myositis patients) participated in this study. Wave amplitude was determined along a linear profile through the center of the muscle, and an exponential decay curve was fit to the data. This measure was able to find significant differences in attenuation between healthy and diseased muscle. Furthermore, four hyperthyroid myopathy subjects who were tested following treatment all showed improvement by this measure. A likely reason for patients with hyperthyroid myopathy and myositis behaving similarly is that this measurement may reflect similar changes in the muscle extracellular matrix. In addition to modulus, attenuation seems to be an important parameter to measure in skeletal muscle. Further research is needed to investigate other potential measures of attenuation as well as examining other potential measures that can be found from visualizing wave propagation. Future studies should also include muscle biopsies to confirm that the changes seen are as a result of changes in extracellular matrix structure. [Copyright &y& Elsevier]

We have cloned the proto-oncogene c-fos from a self-fertilizing fish Rivulus marmoratus (Cyprinodontiformes, Rivulidae) after screening of R. marmoratus λGEM-11 genomic DNA library, and sequenced over 12 kb including all exons, introns and the promoter region. The R. marmoratus c-fos gene consisted of one noncoding exon and four exons with high similarity to those of fugu and mammals. We sequenced ≈7 kb of the R. marmoratus c-fos gene promoter region to gain a better understanding of the molecular anatomy of the immediate response of this gene upon cellular damage. In the promoter region, R. marmoratus c-fos gene has seven xenobiotic response elements (XREs) and eight metal response elements (MREs) as well as two estradiol (E2), 4 NFκB, 2 CarG, 2 prolactin (PRL) motifs and one pit1 site, while the 3′-UTR of this gene contains the estrogen response element (ERE). The seven XRE and eight MRE motifs raise the possibility of its regulation by exposure to environmental pollutants. In this paper, we discuss the gene structure of R. marmoratus c-fos gene and compare its promoter region with those of other organisms'' c-fos genes. We propose its potential use in ecotoxicology. [Copyright &y& Elsevier]

Nonalcoholic fatty liver disease (NAFLD) is estimated to afflict approximately 1 billion individuals worldwide. In a subset of NAFLD patients, who have the progressive form of NAFLD termed nonalcoholic steatohepatitis (NASH), it can progress to advanced fibrosis, cirrhosis, hepatocellular carcinoma, and liver-related morbidity and mortality. NASH is typically characterized by a specific pattern on liver histology, including steatosis, lobular inflammation, and ballooning with or without peri-sinusoidal fibrosis. Thus, key issues in NAFLD patients are the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis. Until now, liver biopsy has been the gold standard for identifying these 2 critical end points, but has well-known limitations, including invasiveness; rare but potentially life-threatening complications; poor acceptability; sampling variability; and cost. Furthermore, due to the epidemic proportion of individuals with NAFLD worldwide, liver biopsy evaluation is impractical, and noninvasive assessment for the diagnosis of NASH and fibrosis is needed. Although much of the work remains to be done in establishing cost-effective strategies for screening for NASH, advanced fibrosis, and cirrhosis, in this review, we summarize the current state of the noninvasive assessment of liver disease in NAFLD, and we provide an expert synthesis of how these noninvasive tools could be utilized in clinical practice. Finally, we also list the key areas of research priorities in this area to move forward clinical practice. [ABSTRACT FROM AUTHOR]

Summary The MEF2 family of transcription factors restricts excitatory synapse number in an activity-dependent fashion during development, yet MEF2 has not been implicated in long-term synaptic depression (LTD), which is thought to initiate synapse elimination. Mutations in MEF2 pathways are implicated in autism spectrum disorders, which include cerebellar dysfunction. Here, we test the hypothesis that cerebellar LTD requires postsynaptic activation of MEF2. Knockdown of MEF2D produces suppression of the transcription-dependent late phase of LTD in cultured Purkinje cells. The late phase of LTD is also completely blocked in Purkinje cells derived from MEF2A+MEF2D null mice and rescued with plasmids that drive expression of MEF2D but not phosphatase-resistant mutant MEF2D S444D. Wild-type Purkinje cells transfected with a constitutively active form of MEF2 show no alterations of synaptic strength. Thus, postsynaptic activation of MEF2 by S444 dephosphorylation is necessary, but not sufficient, for the late phase of cerebellar LTD. Graphical Abstract Highlights • Knockdown or deletion of postsynaptic MEF2 blocks the late phase of cerebellar LTD • Purkinje cells transfected with active MEF2 show normal synaptic strength • Activation of MEF2 is necessary, but not sufficient, for the late phase of LTD Neurodevelopmental disorders can reflect defects in synaptic pruning, which is thought to require activity-dependent weakening of synapses, a process called long-term depression. Andzelm et al. show that MEF2, which is important for neuronal development, is required for the late phase of long-term depression in the cerebellum. [ABSTRACT FROM AUTHOR]