Charged Body Research Articles

Electrostatically Induced Voltage Generated in Ungrounded Metal Boxes and on a Metal Box When a Charged Body Moves Away from the Box

Electrostatically Induced Voltage Generated in Ungrounded Metal Boxes and on a Metal Box When a Charged Body Moves Away from the Box

Abstract LB-047: CHMP5 dependency is a therapeutic vulnerability of T cell acute lymphoblastic leukemia

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is a very aggressive hematologic malignancy that results from the transformation of immature T-cell progenitors. Aberrant cell growth and proliferation is sustained by strong oncogenic drivers, notably NOTCH1 and MYC, whose activation is present in more than half of all T-ALL cases. However, although it is known that post-translational modifications, such as ubiquitination by the E3-ligase FBXW7, regulate NOTCH1 and MYC protein stability and activity, regulatory proteins involved in their stability remain unestablished. The Charged multivesicular body protein 5 (CHMP5), an accessory protein of the ESCRT (endosomal sorting complex required for transport) pathway, has been shown to regulate the stability of client proteins in thymocytes through the recruitment of de-ubiquitinating enzymes. Here, we report that CHMP5 protein is not only highly expressed in T-ALL cells, but also promotes the stability of transactivating intracellular NOTCH1 (ICN1) and MYC. We found that depletion of CHMP5 significantly reduced the abundance of ICN1 and MYC, and the transcription of their target genes in vitro, as well as suppressed the development of T-ALL in vivo in a murine model of NOTCH1 driven T-ALL. Additionally, loss of CHMP5 restored T-ALL cell susceptibility to chemotherapeutic agents, including glucocorticoids and gamma secretase inhibitors, resistance to which contributes to disease relapse in patients. We further reveal CHMP5 as an adaptor protein required to orchestrate T-ALL client protein deubiquitination and stability. Altogether, our data suggest that CHMP5 is a non-oncogenic dependency of T-ALL and its depletion may be an effective therapeutic strategy for T-ALL. Citation Format: Katharine Umphred-Wilson, Stanley Adoro. CHMP5 dependency is a therapeutic vulnerability of T cell acute lymphoblastic leukemia [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-047.

Ionospheric drag for accelerated deorbit from upper low earth orbit

Orbit debris mitigation restrictions placed on the growing number of miniaturised spacecraft often constrain their operational altitudes to less than approximately 600km where drag accelerations are sufficient to deorbit the spacecraft within 25 year guidelines. Operation at higher, Low Earth Orbit (LEO) altitudes often necessitates active measures to deorbit miniaturised spacecraft such as propulsion systems. However, the inclusion of propulsion systems is not always desirable because of the added cost and complexity. This work investigates the feasibility of ionospheric drag, the component of drag caused by an electrically charged body’s exchange of momentum with the ionosphere, to accelerate the deorbit of miniaturised spacecraft in high LEO (600–1000 km altitude). This work studies how actively charging the surface of a miniaturised satellite in high LEO may enhance the overall magnitude of the drag acceleration, due to the ionospheric drag, acting to deorbit the spacecraft. This is achieved using surrogate models of the charged drag coefficient, as a function of plasma scaling parameters, generated by Particle-in-Cell simulations. The charged drag coefficient surrogate model is incorporated into an orbit propagator where deorbit times are predicted over various orbital and vehicular initial conditions. Results suggest that the magnitude of ionospheric drag can be an order of magnitude larger than the neutral drag at 850 km altitude compared to approximately half the magnitude of neutral drag at 500 km altitude. Therefore, ionospheric drag is relatively more efficient at deorbiting spacecraft at high LEO compared to neutral drag. Additionally, the magnitude of ionospheric drag is tailorable based on changes in the electrical surface potential of the satellite relative to a quasi-neutral free-stream plasma. The primary payload of many miniaturised spacecraft often require high-voltage electrical systems. These same electrical systems could conceivably be utilised to generate ionospheric drag via surface charging, at the end of the mission-life, at little additional cost or system complexity. Thus, the implications of this work include the possible uncovering of a simple mechanism for deorbiting miniaturised spacecraft from high LEO altitudes for compliance with orbit debris mitigation guidelines.

Up-regulation of CHMP4B alleviates microglial necroptosis induced by traumatic brain injury.

Microglial cells are key component of central nervous system (CNS) and mediate the immune response of the brain under physiological or pathological conditions. It tends to activate into a pro‐inflammatory M1 phenotype after traumatic brain injury (TBI) and promote secondary brain damage. Recently, necroptosis was found to promote microglial activation and neuroinflammation after TBI. However, the mechanism and specific interventions of microglial necroptosis after TBI remain poorly investigated. Here, we reported that overexpress the charged multivesicular body protein 4b (CHMP4B) which is a core member of the endosomal sorting required for transport complex III (ESCRT‐III) significantly decreased the level of necroptosis in microglia, improved neurological function recovery and protected against cell death after TBI. Further investigation showed that forkhead transcription factor O1 (FOXO1) was a crucial transcription factor that increased CHMP4B transcription by binding to the promoter region, thereby inhibiting necroptosis in microglia. Collectively, our findings demonstrated that CHMP4B relieved microglial necroptosis and neuroinflammation after TBI, and promote the recovery of nerve function. FOXO1 is an important factor in promoting CHMP4B expression. This study provides the novel viewpoint for TBI prevention and treatment.

The asymptotic solutions of the governing system of a charged symmetric body under the influence of external torques

This paper investigates the motion of a dynamically symmetric rigid body about one of its fixed points in which it is incurred to Newtonian force field, electromagnetic field and external torques. These torques acted in the direction of the principal axes of the body and are represented by perturbing and gyrostatic torques. The body rotates initially about the symmetry dynamic axis with high angular velocity. Therefore, a small parameter can be introduced. The averaging method is applied to convert the governing system of motion into another convenient averaging one in terms of a small parameter. The asymptotic analytical solutions of the latter system are obtained for some distinct applications depending upon the perturbing torques and the restoring one. The good effect of the body parameters on the motion is clarified in the graphical representations of the obtained solutions of the considered applications. The significance of this work is due to its great implementation of practical life like submarines, devices that maintain the stability and measure the orientations of airplanes and for several physics and engineering applications.

Precision measurement of few charges in cavity optoelectromechanical system

An efficient scheme for detecting charge numbers of nearby charged body is presented in the cavity optoelectromechanical system. This is realized by means of the sensitive relationship between the charge number and the measured photon number. The proposed scheme is feasible with experimentally accessible values and is applicable to precision measurement of electrical charge.

ESCRT Machinery Mediates Cytokinetic Abscission in the Unicellular Red Alga Cyanidioschyzon merolae.

In many eukaryotes, cytokinesis proceeds in two successive steps: first, ingression of the cleavage furrow and second, abscission of the intercellular bridge. In animal cells, the actomyosin contractile ring is involved in the first step, while the endosomal sorting complex required for transport (ESCRT), which participates in various membrane fusion/fission events, mediates the second step. Intriguingly, in archaea, ESCRT is involved in cytokinesis, raising the hypothesis that the function of ESCRT in eukaryotic cytokinesis descended from the archaeal ancestor. In eukaryotes other than in animals, the roles of ESCRT in cytokinesis are poorly understood. To explore the primordial core mechanisms for eukaryotic cytokinesis, we investigated ESCRT functions in the unicellular red alga Cyanidioschyzon merolae that diverged early in eukaryotic evolution. C. merolae provides an excellent experimental system. The cell has a simple organelle composition. The genome (16.5 Mb, 5335 genes) has been completely sequenced, transformation methods are established, and the cell cycle is synchronized by a light and dark cycle. Similar to animal and fungal cells, C. merolae cells divide by furrowing at the division site followed by abscission of the intercellular bridge. However, they lack an actomyosin contractile ring. The proteins that comprise ESCRT-I–IV, the four subcomplexes of ESCRT, are partially conserved in C. merolae. Immunofluorescence of native or tagged proteins localized the homologs of the five ESCRT-III components [charged multivesicular body protein (CHMP) 1, 2, and 4–6], apoptosis-linked gene-2-interacting protein X (ALIX), the ESCRT-III adapter, and the main ESCRT-IV player vacuolar protein sorting (VPS) 4, to the intercellular bridge. In addition, ALIX was enriched around the cleavage furrow early in cytokinesis. When the ESCRT function was perturbed by expressing dominant-negative VPS4, cells with an elongated intercellular bridge accumulated—a phenotype resulting from abscission failure. Our results show that ESCRT mediates cytokinetic abscission in C. merolae. The fact that ESCRT plays a role in cytokinesis in archaea, animals, and early diverged alga C. merolae supports the hypothesis that the function of ESCRT in cytokinesis descended from archaea to a common ancestor of eukaryotes.

Dynamics of localized continuum inside a charged particle

This article explains how a charged body can retain its integrity despite electrostatic repulsion within itself. The study requires derivation of the field equations governing the velocity of any arbitrary element within the system. These relations are obtained from two Lagrangian principles based on obvious and least disruptive modifications of known concepts in classical mechanics. The two Lagrangians lead to a relativistic energy-momentum equation describing the motion and Maxwell’s equations quantifying the electromagnetic fields, respectively. The energy-momentum relation shows that rigid body motions creating stationary fields in a rotating frame is a viable solution for the velocity inside the continuum. It also yields a combined potential which remains constant throughout the rotating particle. This constancy coupled with Maxwell’s equations and boundary conditions for proper interfacial continuity provides the charge distribution and geometric shape required for continued coherence of the domain. The paper presents specific simulations for slender annuli steadily rotating about the axis of symmetry where the charge density and the axial width are plotted as radial functions. Curiously, when the analysis is extended to systems with different axes of rotation and symmetry, the proportionalities between energy and frequency as well as momentum and wave-number can be established. Such results are very similar to Planck’s and de Broglie’s laws, even though derived from classical principles. Thus, the presented theory might have deeper implications like, for example, in mathematical computation of fine structure constant.

Practical Papers, Articles and Application Notes

With the advancements of robotic technology, robots have been widely deployed in factory automation and health care. One of the major applications of robots in health care is the myoelectric artificial hand. It consists of a myoelectric signal detector connected to a motor-controlled artificial hand driving unit by wires. In the near future, they will be connected wirelessly for convenience but this may pose an EMI risk to the normal operation of the artificial hand. One possible source of EMI is the electrostatic discharge (ESD) from a charged human body. As the malfunction of a myoelectric artificial hand due to ESD has a direct impact on human life, high immunity performance is required. Yasuhiro Morinaga, Keinosuke Nagai, Jianqing Wang and Daisuke Anzai from Nagoya Institute of Technology, Japan, look into this impact and propose design improvements to enhance the immunity of the myoelectric artificial hand against ESD in the paper “Impact of Electrostatic Discharge on Wearable Robotic Hand and Improvement of Immunity Performance by Wireless Control.”

MiR-17 regulates the proliferation and differentiation of retinal progenitor cells by targeting CHMP1A

MicroRNAs have a vital effect on the differentiation of many types of progenitor cells. Recent studies have suggested that miR-17 plays an important role in the differentiation process of brain neural progenitor cells (NPC). Nevertheless, its detailed functions in regulating retinal progenitor cells (RPC) remain unclear. In our study, overexpression and knockdown of miR-17 were performed by transfecting RPC with mimics and inhibitors, respectively. Next, we investigated the role of miR-17 in RPC proliferation and differentiation by the following experiments: qPCR, CCK8, Edu staining, immunostaining and Western blot. The results revealed that miR-17 inhibited RPC proliferation but enhanced differentiation. Furthermore, according to a web-based database analysis, we identified charged multivesicular body protein 1A (CHMP1A) as a target gene. A dual luciferase reporter system showed that miR-17 specifically binds to the CHMP1A 3’ untranslated region (UTR). Next, our data showed upregulation of miR-17 decreased CHMP1A protein level, causing reduced proliferation and enhanced differentiation of RPC. Downregulation of miR-17 led to enhanced CHMP1A protein expression, increased RPC proliferation and decreased differentiation. Taken together, our data provide a proven pathway by which miR-17 regulates RPC proliferation and differentiation by targeting CHMP1A.

Coordinated alteration of mRNA-microRNA transcriptomes associated with exosomes and fatty acid metabolism in adipose tissue and skeletal muscle in grazing cattle.

ObjectiveOn the hypothesis that grazing of cattle prompts organs to secrete or internalize circulating microRNAs (c-miRNAs) in parallel with changes in energy metabolism, we aimed to clarify biological events in adipose, skeletal muscle, and liver tissues in grazing Japanese Shorthorn (JSH) steers by a transcriptomic approach.MethodsThe subcutaneous fat (SCF), biceps femoris muscle (BFM), and liver in JSH steers after three months of grazing or housing were analyzed using microarray and quantitative polymerase chain reaction (qPCR), followed by gene ontology (GO) and functional annotation analyses.ResultsThe results of transcriptomics indicated that SCF was highly responsive to grazing compared to BFM and liver tissues. The ‘Exosome’, ‘Carbohydrate metabolism’ and ‘Lipid metabolism’ were extracted as the relevant GO terms in SCF and BFM, and/or liver from the >1.5-fold-altered mRNAs in grazing steers. The qPCR analyses showed a trend of upregulated gene expression related to exosome secretion and internalization (charged multivesicular body protein 4A, vacuolar protein sorting-associated protein 4B, vesicle associated membrane protein 7, caveolin 1) in the BFM and SCF, as well as upregulation of lipolysis-associated mRNAs (carnitine palmitoyltransferase 1A, hormone-sensitive lipase, perilipin 1, adipose triglyceride lipase, fatty acid binding protein 4) and most of the microRNAs (miRNAs) in SCF. Moreover, gene expression related to fatty acid uptake and inter-organ signaling (solute carrier family 27 member 4 and angiopoietin-like 4) was upregulated in BFM, suggesting activation of SCF-BFM organ crosstalk for energy metabolism. Meanwhile, expression of plasma exosomal miR-16a, miR-19b, miR-21-5p, and miR-142-5p was reduced. According to bioinformatic analyses, the c-miRNA target genes are associated with the terms ‘Endosome’, ‘Caveola’, ‘Endocytosis’, ‘Carbohydrate metabolism’, and with pathways related to environmental information processing and the endocrine system.ConclusionExosome and fatty acid metabolism-related gene expression was altered in SCF of grazing cattle, which could be regulated by miRNA such as miR-142-5p. These changes occurred coordinately in both the SCF and BFM, suggesting involvement of exosome in the SCF-BFM organ crosstalk to modulate energy metabolism.

Entropy bounds and nonlinear electrodynamics

Bekenstein's inequality sets a bound on the entropy of a charged macroscopic body. Such a bound is understood as a universal relation between physical quantities and fundamental constants of nature that should be valid for any physical system. We reanalyze the steps that lead to this entropy bound considering a charged object in conformity to Born-Infeld electrodynamics and show that the bound depends of the underlying theory used to describe the physical system. Our result shows that the nonlinear contribution to the electrostatic self-energy causes a raise in the entropy bound. As an intermediate step to obtain this result, we exhibit a general way to calculate the form of the electric field for a given nonlinear electrodynamics in Schwarzschild spacetime.

Compromised function of the ESCRT pathway promotes endolysosomal escape of tau seeds and propagation of tau aggregation

Intercellular propagation of protein aggregation is emerging as a key mechanism in the progression of several neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia (FTD). However, we lack a systematic understanding of the cellular pathways controlling prion-like propagation of aggregation. To uncover such pathways, here we performed CRISPR interference (CRISPRi) screens in a human cell-based model of propagation of tau aggregation monitored by FRET. Our screens uncovered that knockdown of several components of the endosomal sorting complexes required for transport (ESCRT) machinery, including charged multivesicular body protein 6 (CHMP6), or CHMP2A in combination with CHMP2B (whose gene is linked to familial FTD), promote propagation of tau aggregation. We found that knocking down the genes encoding these proteins also causes damage to endolysosomal membranes, consistent with a role for the ESCRT pathway in endolysosomal membrane repair. Leakiness of the endolysosomal compartment significantly enhanced prion-like propagation of tau aggregation, likely by making tau seeds more available to pools of cytoplasmic tau. Together, these findings suggest that endolysosomal escape is a critical step in tau propagation in neurodegenerative diseases.

ESCRT subunit CHMP4B localizes to primary cilia and is required for the structural integrity of the ciliary membrane.

Proteins specialized in the detection, generation, or stabilization of membrane curvature play important roles in establishing various morphologies of cells and cellular organelles. Primary cilia are cellular organelles that protrude from the cell surface using a microtubule-based cytoskeleton called the axoneme as a structural support. It is unclear whether the integrity of the high curvature of the ciliary membrane depends on membrane curvature-related proteins. Charged Multivesicular Body Protein 4B (CHMP4B), a subunit of the endosomal sorting complexes required for transport (ESCRT), can stabilize membrane curvature. Here we show that CHMP4B is involved in the assembly and maintenance of primary cilia. CHMP4B was localized to primary cilia in mammalian cells. Knockdown of CHMP4B interfered with cilium assembly and also caused fragmentation of preexisting cilia. By contrast, cilium formation was unaffected by the interruption of the ESCRT-dependent endocytic degradation pathway. Morpholino (MO)-mediated CHMP4B depletion in zebrafish embryos induced characteristic phenotypes of ciliary defects such as curved body axis, hydrocephalus, otolith malformation, and kidney cyst. Our study reveals a new role for the multifunctional protein CHMP4B as a key factor in maintaining the structural integrity of primary cilia.

Monotonicity formulas in potential theory

Using the electrostatic potential u due to a uniformly charged body $$\Omega \subset {\mathbb {R}}^n$$, $$n\ge 3$$, we introduce a family of monotone quantities associated with the level set flow of u. The derived monotonicity formulas are exploited to deduce a new quantitative version of the classical Willmore inequality.

Spin self-force

We consider the motion of charged and spinning bodies on the symmetry axis of a non-extremal Kerr-Newman black hole. If one treats the body as a test point particle of mass, $m$, charge $q$, and spin $S$, then by dropping the body into the black hole from sufficiently near the horizon, the first order area increase, $\delta A$, of the black hole can be made arbitrarily small, i.e., the process can be done in a ``reversible'' manner. At second order, there may be effects on the energy delivered to the black hole---quadratic in $q$ and $S$---resulting from (i) the finite size of the body and (ii) self-force corrections to the energy. Sorce and Wald have calculated these effects for a charged, non-spinning body on the symmetry axis of an uncharged Kerr black hole. We consider the generalization of this process for a charged and spinning body on the symmetry axis of a Kerr-Newman black hole, where the self-force effects have not been calculated. A spinning body (with negligible extent along the spin axis) must have a mass quadrupole moment $\gtrsim S^2/m$, so at quadratic order in the spin, we must take into account quadrupole effects on the motion. After taking into account all such finite size effects, we find that the condition $\delta^2 A \geq 0$ yields a nontrivial lower bound on the self-force energy, $E_{SF}$, at the horizon. In particular, for an uncharged, spinning body on the axis of a Kerr black hole of mass $M$, the net contribution of spin self-force to the energy of the body at the horizon is $E_{SF} \geq S^2/8M^3$, corresponding to an overall repulsive spin self-force. A lower bound for the self-force energy, $E_{SF}$, for a body with both charge and spin at the horizon of a Kerr-Newman black hole is given. This lower bound will be the correct formula for $E_{SF}$ if the dropping process can be done reversibly to second order.

Multisphere Method for Flexible Conducting Space Objects: Modeling and Experiments

In the last two decades, concepts have been developed to harness electrostatic forces and torques to enable novel missions, including coulomb formation flying, inflating membrane structures, and detumbling and reorbiting debris touchlessly. The need for faster-than-real-time modeling of the electrostatic forces and torques in these missions has led to the development of the multisphere method (MSM) in which the electrostatic field generated by a charged body is approximated through the use of a series of optimally placed and sized conducting spheres. Although the prior work assumed the charged body was rigid, this paper extends the use of the MSM to flexible shapes. An example of the effectiveness of the MSM approach is explored by matching analytical models of the electric field and capacitance about a line of charge, and then deforming it into a ring while still matching analytic models. However, the core underlying assumption of the shape surface being a conductor remains. The limits of this model are tested via experimental comparison of a thin strip of aluminized Mylar in a constant electric field with the flexible MSM model. Although the new flexible MSM is good at modeling time-varying shapes of pure conductors, the charged thin Mylar sheet dynamics are strongly influenced by dielectric polarization and charge self-emission due to the sharp edges.

Precision measurement of electrical charge in a hybrid optomechanical system with Michelson interferometer

In this work, we present a scheme to measure electrical charge by combining a cavity optomechanical system with Michelson interferometer. The optomechanical cavity with a charged movable mirror is placed in one arm of a Michelson interferometer, in which the cavity length is modified due to the Coulomb force between the charged moveable mirror with the unknown charge and the charged body with the known charge, leading to a change in the output of the cavity mode. In addition, a perfectly reflecting mirror is rigidly fixed in the other arm. The unknown electrical charge can be measured by the difference of output intensities in both arms of the Michelson interferometer. The theoretical derivation and the numerical simulation indicate our scheme is more sensitive to the external Coulomb force and the precision of the scheme can reach unity charge, due to resorting to the Michelson interferometer. Besides, the effect of temperature on the sensitivity of electrical charge detector is also discussed.

Structural Insights into AQP2 Targeting to Multivesicular Bodies.

Vasopressin-dependent trafficking of AQP2 in the renal collecting duct is crucial for the regulation of water homeostasis. This process involves the targeting of AQP2 to the apical membrane during dehydration as well as its removal when hydration levels have been restored. The latter involves AQP2 endocytosis and sorting into multivesicular bodies (MVB), from where it may be recycled, degraded in lysosomes, or released into urine via exosomes. The lysosomal trafficking regulator-interacting protein 5 (LIP5) plays a crucial role in this by coordinating the actions of the endosomal sorting complex required for transport III (ESCRT-III) and vacuolar protein sorting 4 (Vps4) ATPase, resulting in the insertion of AQP2 into MVB inner vesicles. While the interaction between LIP5 and the ESCRT-III complex and Vps4 is well characterized, very little is known about how LIP5 interacts with AQP2 or any other membrane protein cargo. Here, we use a combination of fluorescence spectroscopy and computer modeling to provide a structural model of how LIP5 interacts with human AQP2. We demonstrate that, the AQP2 tetramer binds up to two LIP5 molecules and that the interaction is similar to that seen in the complex between LIP5 and the ESCRT-III component, charged multivesicular body protein 1B (CHMP1B). These studies give the very first structural insights into how LIP5 enables membrane protein insertion into MVB inner vesicles and significantly increase our understanding of the AQP2 trafficking mechanism.

Study of gravitational deflection of light ray

Gravitational deflection of light ray is one of the famous predictions of Einstein’s general theory of relativity. The deflection of light ray, as it passes around a gravitational mass, can be calculated by different methods such as null geodesics method and material medium approach. In this paper a comparative study will be done for gravitational deflection of light ray, calculated by different authors using different methods. In this study, different gravitating body such as static, rotating and charged body will be considered which are represented by Schwarzschild metric, Kerr metric, Reissner-Nordström metric and Janis-Newman-Winicour metric.