In view of their unique shape morphing behaviour, dielectric elastomer-based minimum energy structures (DEMES) have received an increasing attention in the technology of electroactive soft ...transduction. Because several of them undergo a time-dependent motion during their operation, understanding their nonlinear dynamic behaviour is crucial to their effective design. Additionally, in the recent past, there has been a growing scientific interest in imparting anisotropy to the material behaviour of dielectric elastomers in view of ameliorating their actuation performance. Spurred with these ongoing efforts, this paper presents an analytical framework for investigating the nonlinear dynamic behaviour of aniso-visco-hyperelastic DEMES actuator with an elementary rectangular geometry. We use a rheological model comprising two Maxwell elements connected in parallel with two single spring elements for modelling the material behaviour of the DE membrane. The governing equations of motion for the underlying non-conservative system are then derived using the Euler–Lagrange equation. The proposed model is used for building insights into the attainable equilibrium states, periodicity of the response as well as the resonant behaviour of the DEMES actuator over a feasible range of anisotropy and viscosity parameters. Our results reveal that the DEMES with hyperelastic material properties exhibits a supercritical pitchfork bifurcation of equilibrium state which is further accelerated in terms of attained equilibrium angle due to membrane anisotropy. A significant enhancement in the equilibrium angle attained by the structure with the extent of membrane anisotropy parameter is observed, indicating a favourable impact of material anisotropy. Poincare maps and phase-portraits are presented for assessing the periodicity of the nonlinear oscillations. The frequency response of the actuator for a combined DC and AC load indicates an upsurge in the resonant frequency with an increase in anisotropy parameter. The underlying analytical model and the trends presented in this study can find their potential use in the design and development of the futuristic anisotropic DEMES actuators subjected to time-dependent actuation.
Soft materials exhibiting large deformation under external stimuli have gained an increasing attention in the recent past because of their potential applications in soft transducers aimed at ...achieving biomimetic actuation. This paper theoretically analyzes the effect of internal properties, including entanglements, crosslinks and finite extensibility of polymer chains along with inherent viscoelastic properties of polymers on the performance of Dielectric Elastomer actuator (DEA) in dynamic modes of actuation. A physics based nonaffine material model proposed by Davidson and Goulbourne is used to model the polymer chains entanglements, crosslinks and finite extensibility. To incorprate the viscoelastic properties, a rheological material model based on the additive decomposition of the isotropic strain energy density into equilibrium and viscous parts is implemented. A computationally efficient method, which relies on the principle of least action is used for extracting the governing equation representing the dynamic motion of the DE actuator. The results demonstrate that DEAs with strong entanglements and crosslinks along with small finite extensibility of polymer chains exhibits lower deformation level in DC dynamic modes of actuation. It is inferred that the strong entanglements and crosslinks in polymer chains enhances the resonant frequency, but debilitate the intensity of vibration of viscoelastic DEAs. Further, the periodicity and stability of the nonlinear oscillations exhibited by the viscoelastic DEAs are assessed by employing the Poincare maps and phase portraits. The results of the present investigation can be applied effectively in bridging the mechanism between the microcosmic polymer chains and macroscopic dynamic behavior of viscoelastic DE actuators.
Dielectric elastomers are among the soft active materials that may achieve substantial actuation strains when subjected to a high electric field. The material behavior of such elastomers is greatly ...influenced by environmental humidity. In this paper, we extend upon our previous dynamic modeling frameworks (Khurana et al. in Nonlinear Dyn 104(2):1227–1251, 2021, Sharma and Joglekar in Comput Methods Appl Mech Eng 344:402–420, 2019) to incorporate the effect of humidity in the material model and investigate its effect on the dynamic electromechanical behavior of a transversely isotropic dielectric viscoelastomer actuator with entangled polymer chains. The governing dynamic equation is developed using the non-conservative Euler–Lagrange equation. The proposed model is used for building insights into the effect of membrane humidity on the dynamic behavior and pull-in instability phenomena of the viscoelastomer actuator over a feasible range of anisotropy and entanglement parameters. The results indicate that dielectric elastomer actuators with higher humidity levels have a higher level of deformation and lower electric field at the pull-in point in the DC dynamic mode of actuation, indicating a favorable impact of material humidity. The reduction of critical electric field due to humidity changes can be minimized by integrating the material anisotropy as per the tropical humidity condition. In addition, the Poincaré maps and phase portraits are also plotted to assess the stability, periodicity of the response as well as resonant behavior of the actuator. It is inferred that the higher humidity level of entangled polymer chains diminishes the resonance excitation frequency, which can be further tuned by incorporating material anisotropy. In general, the current study provides initial steps toward the modern actuator designs taking into account the combined effect of humidity conditions, entanglement, and the anisotropic nature of the membrane, which can be effectively implemented for various futuristic applications in the engineering and medical field.
The success of several cell-based therapies and prevalent use of magnetic resonance imaging (MRI) in the clinic has fueled the development of contrast agents for specific cell tracking applications. ...Safe and efficient labeling of non-phagocytic cell types such as T cells nonetheless remains challenging. We developed a one-stop shop approach where the T cell sorting agent also labels the cells which can subsequently be depicted using non-invasive MRI. We compared the MR signal effects of magnetic-assisted cell sorting microbeads (CD25) to the current preclinical gold standard, ferumoxytol. We investigated in vitro labeling efficiency of regulatory T cells (Tregs) with MRI and histopathologic confirmation. Thereafter, Tregs and T cells were labeled with CD25 microbeads in vitro and delivered via intravenous injection. Liver MRIs pre- and 24 h post-injection were performed to determine in vivo tracking feasibility. We show that CD25 microbeads exhibit T2 signal decay properties similar to other iron oxide contrast agents. CD25 microbeads are readily internalized by Tregs and can be detected by non-invasive MRI with dose dependent T2 signal suppression. Systemically injected labeled Tregs can be detected in the liver 24 h post-injection, contrary to T cell control. Our CD25 microbead-based labeling method is an effective tool for Treg tagging, yielding detectable MR signal change in cell phantoms and in vivo. This novel cellular tracking method will be key in tracking the fate of Tregs in inflammatory pathologies and solid organ transplantation.
Regulatory T cells (Tregs) are essential to maintain self-tolerance and immune homeostasis but, as components of the tumor microenvironment (TME), are also a major barrier to effective cancer ...immunosurveillance and immunotherapy. FH535 and its derivative Y3 are two N-aryl-benzene-sulfonamides (NABs) that inhibit HCC cell proliferation and tumor progression. However, the impact of NABs on the immune cells in the TME is not yet known. Analyses of explanted livers from patients with hepatocellular carcinoma (HCC) showed that high levels of tumor-infiltrating Tregs were associated with poor tumor differentiation. These results lead us to investigate the immunomodulatory effects of NABs in regulatory and effector T cells. Exposure of primary human Tregs to NABs induced a rapid but temporary increase of cell expansion, a gradual disruption of suppressor activity, and concomitant bioenergetics and autophagic flux dysregulations. In contrast to Tregs, no gross effects were observed in effector T cells. Addition of Rapamycin prevented the functional decay of Tregs and restored their metabolic profile, suggesting that NAB effects require the integrity of the mTOR pathway. This study revealed the immunomodulatory properties of NABs with a preferential impact on Treg activity and provided novel insights into the anti-tumor potential of sulfonamides.
Acute pancreatitis has a wide array of imaging presentations. Various classifications have been used in the past to standardize the terminology and reduce confusing and redundant terms. We aim to ...review the historical and current classifications of acute pancreatitis and propose a new reporting template which can improve communication between various medical teams by use of appropriate terminology and structured radiology template. The standardized reporting template not only conveys the most important imaging findings in a simplified yet comprehensive way but also allows structured data collection for future research and teaching purposes.
Background
Solid malignant tumors are more highly cellular than benign lesions and hence have a restricted diffusion of water molecules.
Objective
To evaluate whether diffusion-weighted MR imaging ...(DWI) can differentiate between benign and malignant pediatric abdominal tumors.
Materials and methods
We retrospectively analyzed DWI scans of 68 consecutive children with 39 benign and 34 malignant abdominal masses. To calculate the apparent diffusion coefficient (ADC) maps and ADC values, we used 1.5-T sequences at TR/TE/b-value of 5,250–7,500/54–64/
b
= 0, 500 and 3-T sequences at 3,500–4,000/66–73/
b
= 0, 500, 800. ADC values were compared between benign and malignant and between data derived at 1.5 tesla (T) and at 3 tesla magnetic field strength, using the Mann-Whitney-Wilcoxon test, ANOVA and a receiver operating curve (ROC) analysis.
Results
There was no significant difference in ADC values obtained at 1.5 T and 3 T (
P
= 0.962). Mean ADC values (× 10
−3
mm
2
/s) were 1.07 for solid malignant tumors, 1.6 for solid benign tumors, 2.9 for necrotic portions of malignant tumors and 3.1 for cystic benign lesions. The differences between malignant and benign solid tumors were statistically significant (
P
= 0.000025). ROC analysis revealed an optimal cut-off ADC value for differentiating malignant and benign solid tumors as 1.29 with excellent inter-observer reliability (alpha score 0.88).
Conclusion
DWI scans and ADC values can contribute to distinguishing between benign and malignant pediatric abdominal tumors.
Background: Regulatory T cell (Treg) therapy is considered an alternative approach to induce tolerance in transplantation. If successful, this therapy may have implications on immunosuppression ...minimization/withdrawal to reduce drug-induced toxicity in patients. The aim of this study was to assess the efficacy of the mTORC1/C2 inhibitor, AZD8055, in the manufacturing of clinically competent Treg cells and compare the effects with those induced by rapamycin (RAPA), another mTOR inhibitor commonly used in Treg expansion protocols. Methods: Primary human Treg cells were isolated from leukapheresis product. Cell viability, expansion rates, suppressive function, autophagy, mitochondrial unfolded protein response (mitoUPR), and cell metabolic profile were assessed. Results: We observed a stronger inhibition of the mTORC2 signaling pathway and downstream events triggered by Interleukin 2 (IL2)-receptor in AZD8055-treated cells compared with those treated with RAPA. AZD8055 induced progressive metabolic changes in mitochondrial respiration and glycolytic pathways that disrupted the long-term expansion and suppressive function of Tregs. Unlike RAPA, AZD8055 treatment impaired autophagy and enhanced the mitoUPR cell stress response pathway. Conclusions: A distinct pattern of mTOR inhibition by AZD, compared with RAPA, induced mitochondrial stress response and dysfunction, impaired autophagy, and disrupted cellular bioenergetics, resulting in the loss of proliferative potential and suppressive function of Treg cells.
To evaluate the role of positron emission tomography (PET)/computed tomography (CT) in the differentiation of normal thymus from mediastinal lymphoma and lymphoma recurrence in pediatric patients.
...The study was approved by the institutional review board, and informed consent was waived. The study was HIPAA compliant. Two hundred eighty-two fluorine 18 fluorodeoxyglucose PET/CT studies in 75 pediatric oncology patients were reviewed retrospectively. Patients were divided into four groups: anterior mediastinal lymphoma (group A, n=16), anterior mediastinal lymphoma with subsequent recurrence (group B, n=5), lymphoma outside the mediastinum (group C, n=16), and other malignant tumors outside the thymus (group D, n=38). Analyses included measurements of the maximum anteroposterior and transverse dimensions of the anterior mediastinal mass or thymus on axial CT images and measurements of maximum standardized uptake values of anterior mediastinal mass, thymus (SUVt), and bone marrow at the level of the fifth lumbar vertebra (SUVb) on PET images. Quantitative parameters were compared by using an analysis of variance test.
Mean prechemotherapy SUVt was 4.82 for group A, 8.45 for group B, 2.00 for group C, and 2.09 for group D. Mean postchemotherapy SUVt for group B was 4.74. Thymic rebound (mean SUVt, 2.89) was seen in 44% of patients at a mean interval of 10 months from the end of chemotherapy. The differences between prechemotherapy SUVt of mediastinal lymphoma and normal thymus and postchemotherapy SUVt of lymphoma recurrence and thymic rebound were highly significant (P<.001).
SUVt is a sensitive predictor for differentiation of normal thymus or thymic rebound from mediastinal lymphoma. SUVt of 3.4 or higher is a strong predictor of mediastinal lymphoma.
Objectives To compare the pattern of daily ambulatory activity in men and women with intermittent claudication, and to determine whether calf muscle hemoglobin oxygen saturation (StO2 ) is associated ...with daily ambulatory activity. Methods Forty men and 41 women with peripheral arterial disease limited by intermittent claudication were assessed on their community-based ambulatory activity patterns for 1 week with an ankle-mounted step activity monitor and on calf muscle StO2 during a treadmill test. Results Women had lower adjusted daily maximal cadence (mean ± SE) for 5 continuous minutes of ambulation (26.2 ± 1.2 strides/min vs 31.0 ± 1.2 strides/min; P = .009), for 1 minute of ambulation (43.1 ± 0.9 strides/min vs 47.2 ± 0.9 strides/min; P = .004), and for intermittent ambulation determined by the peak activity index (26.3 ± 1.2 strides/min vs 31.0 ± 1.2 strides/min; P = .009). Women also had lower adjusted time to minimum calf muscle StO2 during exercise ( P = .048), which was positively associated with maximal cadence for 5 continuous minutes ( r = 0.51; P < .01), maximal cadence for 1 minute ( r = 0.42; P < .05), and peak activity index ( r = 0.44; P < .05). These associations were not significant in men. Conclusion Women with intermittent claudication ambulate slower in the community setting than men, particularly for short continuous durations of up to 5 minutes and during intermittent ambulation at peak cadences. Furthermore, the daily ambulatory cadences of women are correlated with their calf muscle StO2 during exercise, as women who walk slower in the community setting reach their minimum calf muscle StO2 sooner than those who walk at faster paces. Women with intermittent claudication should be encouraged to not only walk more on a daily basis, but to do so at a pace that is faster than their preferred speed.
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