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Wang, N.

Publications and source records attributed to Wang, N..

At least 19 records

Measurement of the background in the CMS muon detector in ${p}{p}$-collisions at $\sqrt{s} = 13$ TeV

The CMS detector, including its muon system, has been operating at the CERN LHC in increasingly challenging conditions for about 15 years. The muon detector was designed to provide excellent triggering and track reconstruction for muons produced in proton–proton collisons at an instantaneous luminosity ($\mathcal{L}$) of 1 x 10 34 cm –2 s –1 . During the Run 2 data-taking period (2015–2018), the LHC achieved an instantaneous luminosity of twice its design value, resulting in larger background rates and making the efficient detection of muons more difficult. While some backgrounds result from natural radioactivity, cosmic rays, and interactions of the circulating protons with residual gas in the beam pipe, the dominant source of background hits in the muon system arises from proton–proton interactions themselves. Charged hadrons leaving the calorimeters produce energy deposits in the muon chambers. In addition, high-energy particles interacting in the hadron calorimeter and forward shielding elements generate thermal neutrons, which leak out of the calorimeter and shielding structures, filling the CMS cavern. We describe the method used to measure the background rates in the various muon subsystems. These rates, in conjunction with simulations, can be used to estimate the expected backgrounds in the High-Luminosity LHC. This machine will run for at least 10 years starting in 2029 reaching an instantaneous luminosity of $\mathcal{L}$ = 5 x 10 34 cm –2 s –1 and increasing ultimately to $\mathcal{L}$ = 7.5 x 10 34 cm –2 s –1 . These background estimates have been a key ingredient for the planning and design of the muon detector upgrade.

Tytgat, M. (ORCID:0000000239902074)↗

Beam Dynamics of the Strong Hadron Cooler ERL at the Electron-Ion Collider

The Strong Hadron Cooler Energy Recovery Linac (SHC-ERL) for the Electron-Ion Collider (EIC) is required to produce an electron beam with a bunch charge of 1 nC, an average current of 100 mA, and a beam energy of both 150 and 55 MeV, with strict requirements for the transverse emittance, slice energy spread, and longitudinal distribution. This paper covers the design in detail, including preliminary considerations of higher order effects and diagnostics.

Deitrick, K.↗

Design Overview of the Strong Hadron Cooler ERL at the Electron-Ion Collider

The Electron-Ion Collider (EIC) is currently under development to be built at Brookhaven National Lab and requires cooling during collisions in order to preserve the quality of the hadron beam despite degradation due to intra-beam scattering and beam-beam effect. An Energy Recovery Linac (ERL) is being designed to deliver the necessary electron beam for Coherent electron Cooling (CeC) of the hadron beam, with an electron bunch charge of 1 nC and an average current of 100 mA; two modes of operation are being developed for 150 and 55 MeV electrons, corresponding to 275 and 100 GeV protons. The injector of this Strong Hadron Cooler ERL (SHC-ERL) is shared with the Injection Cooler ERL, which cools lower energy proton beams via bunched beam cooling, as used in the Low Energy RHIC electron Cooling (LEReC). This talk introduces the layout and presents a high-level overview of the design.

Deitrick, K.↗

RESONANT MATCHING SECTION FOR CEBAF ENERGY UPGRADE

In order to prevent emittance growth during long stores of the proton beam at the future Electron-Ion Collider (EIC), we need to have some mechanism to provide fast cooling of the dense proton beams. One promising method is coherent electron cooling (CeC), which uses an electron beam to both ?measure? the positions of protons within the bunch and then apply energy kicks which tend to reduce their longitudinal and transverse actions. In this work, we discuss the under- lying physics of this process. We then discuss simulations which constrain the electrons to move only longitudinally in order to perform fast optimizations and long-term track- ing of the bunch evolution, and benchmark these results against fully 3D codes. Additionally, we discuss practical challenges, including the necessity of a high-quality elec- tron beam and sub-micron alignment of the electrons and protons.

Deitrick, K.↗

OPTIMIZATION OF COOLING DISTRIBUTION OF THE EIC SHC COOLER ERL

The Electron-Ion Collider (EIC) Hadron Storage Ring (HSR) will use strong hadron cooling to maintain the beam brightness and high luminosity during long collision ex?periments. An Energy Recovery Linac is used to deliver the high-current high-brightness electron beam for cooling. For the best cooling effect, the electron beam requires low emittance, small energy spread, and uniform longitudinal distribution. In this work, we simulate and optimize the longitudinal laser-beam distribution shaping at the photo?cathode, modeling space charge forces accurately. Machine parameters such as RF cavity phases are optimized in con?junction with the beam distribution using a genetic optimizer. We demonstrate improvement of the cooling distribution in key parameters.

Wang, N.↗

Ultrasonic Characterization of Interfaces in Composite Bonds

The inverse determination of imperfect interfaces from reflection spectra of normal and oblique incident ultrasonic waves in adhesive bonds of multidirectional composites is investigated. The oblique measurements are complicated by the highly dispersed nature of oblique wave spectra at frequencies above 3MHz. Different strategies for bond property reconstruction, including a modulation method, are discussed. The relation of measured interfacial spring density to the physico-chemical model of a composite interface described by polymer molecular bonds to emulate loss of molecular strength on an adhesive composite interface is discussed. This potentially relates the interfacial (adhesion) strength (number of bonds at the adhesive substrate interface) to the spring constant (stiffness) area density (flux), which is an ultrasonically measurable parameter.

Wang, N.↗

Mechanical behavior in living cells consistent with the tensegrity model

Alternative models of cell mechanics depict the living cell as a simple mechanical continuum, porous filament gel, tensed cortical membrane, or tensegrity network that maintains a stabilizing prestress through incorporation of discrete structural elements that bear compression. Real-time microscopic analysis of cells containing GFP-labeled microtubules and associated mitochondria revealed that living cells behave like discrete structures composed of an interconnected network of actin microfilaments and microtubules when mechanical stresses are applied to cell surface integrin receptors. Quantitation of cell tractional forces and cellular prestress by using traction force microscopy confirmed that microtubules bear compression and are responsible for a significant portion of the cytoskeletal prestress that determines cell shape stability under conditions in which myosin light chain phosphorylation and intracellular calcium remained unchanged. Quantitative measurements of both static and dynamic mechanical behaviors in cells also were consistent with specific a priori predictions of the tensegrity model. These findings suggest that tensegrity represents a unified model of cell mechanics that may help to explain how mechanical behaviors emerge through collective interactions among different cytoskeletal filaments and extracellular adhesions in living cells.

NASA Discipline Cell Biology↗

Twisting integrin receptors increases endothelin-1 gene expression in endothelial cells

A magnetic twisting stimulator was developed based on the previously published technique of magnetic twisting cytometry. Using ligand-coated ferromagnetic microbeads, this device can apply mechanical stresses with varying amplitudes, duration, frequencies, and waveforms to specific cell surface receptors. Biochemical and biological responses of the cells to the mechanical stimulation can be assayed. Twisting integrin receptors with RGD (Arg-Gly-Asp)-containing peptide-coated beads increased endothelin-1 (ET-1) gene expression by >100%. In contrast, twisting scavenger receptors with acetylated low-density lipoprotein-coated beads or twisting HLA antigen with anti-HLA antibody-coated beads did not lead to alterations in ET-1 gene expression. In situ hybridization showed that the increase in ET-1 mRNA was localized in the cells that were stressed with the RGD-coated beads. Blocking stretch-activated ion channels with gadolinium, chelating Ca2+ with EGTA, or inhibiting tyrosine phosphorylation with genistein abolished twist-induced ET-1 mRNA elevation. Abolishing cytoskeletal tension with an inhibitor of the myosin ATPase, with an inhibitor of myosin light chain kinase, or with an actin microfilament disrupter blocked twisted-induced increases in ET-1 expression. Our results are consistent with the hypothesis that the molecular structural linkage of integrin-cytoskeleton is an important pathway for stress-induced ET-1 gene expression.

Non-NASA Center↗

Impaired mechanical stability, migration and contractile capacity in vimentin-deficient fibroblasts

Loss of a vimentin network due to gene disruption created viable mice that did not differ overtly from wild-type littermates. Here, primary fibroblasts derived from vimentin-deficient (-/-) and wild-type (+/+) mouse embryos were cultured, and biological functions were studied in in vitro systems resembling stress situations. Stiffness of -/- fibroblasts was reduced by 40% in comparison to wild-type cells. Vimentin-deficient cells also displayed reduced mechanical stability, motility and directional migration towards different chemo-attractive stimuli. Reorganization of collagen fibrils and contraction of collagen lattices were severely impaired. The spatial organization of focal contact proteins, as well as actin microfilament organization was disturbed. Thus, absence of a vimentin filament network does not impair basic cellular functions needed for growth in culture, but cells are mechanically less stable, and we propose that therefore they are impaired in all functions depending upon mechanical stability.

Non-NASA Center↗

Differences in elasticity of vinculin-deficient F9 cells measured by magnetometry and atomic force microscopy

We have investigated a mouse F9 embryonic carcinoma cell line, in which both vinculin genes were inactivated by homologous recombination, that exhibits defective adhesion and spreading [Coll et al. (1995) Proc. Natl. Acad. Sci. USA 92, 9161-9165]. Using a magnetometer and RGD-coated magnetic microbeads, we measured the local effect of loss and replacement of vinculin on mechanical force transfer across integrins. Vinculin-deficient F9Vin(-/-) cells showed a 21% difference in relative stiffness compared to wild-type cells. This was restored to near wild-type levels after transfection and constitutive expression of increasing amounts of vinculin into F9Vin(-/-) cells. In contrast, the transfection of vinculin constructs deficient in amino acids 1-288 (containing the talin- and alpha-actinin-binding site) or substituting tyrosine for phenylalanine (phosphorylation site, amino acid 822) in F9Vin(-/-) cells resulted in partial restoration of stiffness. Using atomic force microscopy to map the relative elasticity of entire F9 cells by 128 x 128 (n = 16,384) force scans, we observed a correlation with magnetometer measurements. These findings suggest that vinculin may promote cell adhesions and spreading by stabilizing focal adhesions and transferring mechanical stresses that drive cytoskeletal remodeling, thereby affecting the elastic properties of the cell.

Non-NASA Center↗

Vinculin promotes cell spreading by mechanically coupling integrins to the cytoskeleton

Mouse F9 embryonic carcinoma 5.51 cells that lack the cytoskeletal protein vinculin spread poorly on extracellular matrix compared with wild-type F9 cells or two vinculin-transfected clones (5.51Vin3 and Vin4; Samuels et al., 1993, J. Cell Biol. 121, 909-921). In the present study, we used this model system to determine how the presence of vinculin promotes cytoskeletal alterations and associated changes in cell shape. Microscopic analysis of cell spreading at early times, revealed that 5.51 cells retained the ability to form filopodia; however, they could not form lamellipodia, assemble stress fibers, or efficiently spread over the culture substrate. Detergent (Triton X-100) studies revealed that these major differences in cell morphology and cytoskeletal organization did not result from differences in levels of total polymerized or cross-linked actin. Biochemical studies showed that 5.51 cells, in addition to lacking vinculin, exhibited slightly reduced levels of alpha-actinin and paxillin in their detergent-insoluble cytoskeleton. The absence of vinculin correlated with a decrease in the mechanical stiffness of the integrin-cytoskeleton linkage, as measured using cell magnetometry. Furthermore, when vinculin was replaced by transfection in 5.51Vin3 and 5.51Vin4 cells, the levels of cytoskeletal-associated alpha-actinin and paxillin, the efficiency of transmembrane mechanical coupling, and the formation of actin stress fibers were all restored to near wild-type levels. These findings suggest that vinculin may promote cell spreading by stabilizing focal adhesions and transferring mechanical stresses that drive cytoskeletal remodeling, rather than by altering the total level of actin polymerization or cross-linking.

NASA Program Space Biology↗

Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53 +/- 0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46 +/- 1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97 +/- 1.92 poise in the normally loaded LV cardiocytes to 87.85 +/- 6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload-hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on the cardiocyte contractile apparatus in pressure-overload cardiac hypertrophy.

Non-NASA Center↗

A microstructural approach to cytoskeletal mechanics based on tensegrity

Mechanical properties of living cells are commonly described in terms of the laws of continuum mechanics. The purpose of this report is to consider the implications of an alternative approach that emphasizes the discrete nature of stress bearing elements in the cell and is based on the known structural properties of the cytoskeleton. We have noted previously that tensegrity architecture seems to capture essential qualitative features of cytoskeletal shape distortion in adherent cells (Ingber, 1993a; Wang et al., 1993). Here we extend those qualitative notions into a formal microstructural analysis. On the basis of that analysis we attempt to identify unifying principles that might underlie the shape stability of the cytoskeleton. For simplicity, we focus on a tensegrity structure containing six rigid struts interconnected by 24 linearly elastic cables. Cables carry initial tension ("prestress") counterbalanced by compression of struts. Two cases of interconnectedness between cables and struts are considered: one where they are connected by pin-joints, and the other where the cables run through frictionless loops at the junctions. At the molecular level, the pinned structure may represent the case in which different cytoskeletal filaments are cross-linked whereas the looped structure represents the case where they are free to slip past one another. The system is then subjected to uniaxial stretching. Using the principal of virtual work, stretching force vs. extension and structural stiffness vs. stretching force relationships are calculated for different prestresses. The stiffness is found to increase with increasing prestress and, at a given prestress, to increase approximately linearly with increasing stretching force. This behavior is consistent with observations in living endothelial cells exposed to shear stresses (Wang & Ingber, 1994). At a given prestress, the pinned structure is found to be stiffer than the looped one, a result consistent with data on mechanical behavior of isolated, cross-linked and uncross-linked actin networks (Wachsstock et al., 1993). On the basis of our analysis we concluded that architecture and the prestress of the cytoskeleton might be key features that underlie a cell's ability to regulate its shape.

NASA Discipline Cell Biology↗

A Numerical Analysis of Electromagnetic Scattering from Two-Dimensional Edge Terminations

Several techniques that influence the low frequency scattering from penetrable edge terminations are evaluated using a hybrid finite element and boundary element method code. The edge terminations consist of a dielectric skin forming an exterior shape with an internal conducting bulkhead. Some of the techniques considered are bulkhead shaping, internal material loading, placement of resistive cards, and the placement of lossy dielectric material rods. The intent of the various treatments is to find a combination or combinations that influence(s) the backscattered field to acceptable levels over a range of frequencies for both transverse magnetic and transverse electric polarizations.

Gray, B. E.↗

Cell shape, cytoskeletal mechanics, and cell cycle control in angiogenesis

Capillary endothelial cells can be switched between growth and differentiation by altering cell-extracellular matrix interactions and thereby, modulating cell shape. Studies were carried out to determine when cell shape exerts its growth-regulatory influence during cell cycle progression and to explore the role of cytoskeletal structure and mechanics in this control mechanism. When G0-synchronized cells were cultured in basic fibroblast growth factor (FGF)-containing defined medium on dishes coated with increasing densities of fibronectin or a synthetic integrin ligand (RGD-containing peptide), cell spreading, nuclear extension, and DNA synthesis all increased in parallel. To determine the minimum time cells must be adherent and spread on extracellular matrix (ECM) to gain entry into S phase, cells were removed with trypsin or induced to retract using cytochalasin D at different times after plating. Both approaches revealed that cells must remain extended for approximately 12-15 h and hence, most of G1, in order to enter S phase. After this restriction point was passed, normally 'anchorage-dependent' endothelial cells turned on DNA synthesis even when round and in suspension. The importance of actin-containing microfilaments in shape-dependent growth control was confirmed by culturing cells in the presence of cytochalasin D (25-1000 ng ml-1): dose-dependent inhibition of cell spreading, nuclear extension, and DNA synthesis resulted. In contrast, induction of microtubule disassembly using nocodazole had little effect on cell or nuclear spreading and only partially inhibited DNA synthesis. Interestingly, combination of nocodazole with a suboptimal dose of cytochalasin D (100 ng ml-1) resulted in potent inhibition of both spreading and growth, suggesting that microtubules are redundant structural elements which can provide critical load-bearing functions when microfilaments are partially compromised. Similar synergism between nocodazole and cytochalasin D was observed when cytoskeletal stiffness was measured directly in living cells using magnetic twisting cytometry. These results emphasize the importance of matrix-dependent changes in cell and nuclear shape as well as higher order structural interactions between different cytoskeletal filament systems for control of capillary cell growth during angiogenesis.

Non-NASA Center↗

Material Measurements Using Groundplane Apertures

A technique for material parameter determination using an aperture in a groundplane is studied. The material parameters are found by relating the measured reflected field in the aperture to a numerical model. Two apertures are studied which can have a variety of different material configurations covering the aperture. The aperture cross-sections studied are rectangular and coaxial. The material configurations involved combinations of single layer and dual layers with or without a resistive exterior resistive sheet. The resistivity of the resistive sheet can be specified to simulate a perfect electric conductor (PEC) backing (0 Ohms/square) to a free space backing (infinity Ohms/square). Numerical parameter studies and measurements were performed to assess the feasibility of the technique.

Komisarek, K.↗

Probing transmembrane mechanical coupling and cytomechanics using magnetic twisting cytometry

We recently developed a magnetic twisting cytometry technique that allows us to apply controlled mechanical stresses to specific cell surface receptors using ligand-coated ferromagnetic microbeads and to simultaneously measure the mechanical response in living cells. Using this technique, we have previously shown the following: (i) beta 1 integrin receptors mediate mechanical force transfer across the cell surface and to the cytoskeleton, whereas other transmembrane receptors (e.g., scavenger receptors) do not; (ii) cytoskeletal stiffness increases in direct proportion to the level of stress applied to integrins; and (iii) the slope of this linear stiffening response differs depending on the shape of the cell. We now show that different integrins (beta 1, alpha V beta 3, alpha V, alpha 5, alpha 2) and other transmembrane receptors (scavenger receptor, platelet endothelial cell adhesion molecule) differ in their ability to mediate force transfer across the cell surface. In addition, the linear stiffening behavior previously observed in endothelial cells was found to be shared by other cell types. Finally, we demonstrate that dynamic changes in cell shape that occur during both cell spreading and retraction are accompanied by coordinate changes in cytoskeletal stiffness. Taken together, these results suggest that the magnetic twisting cytometry technique may be a powerful and versatile tool for studies analyzing the molecular basis of transmembrane mechanical coupling to the cytoskeleton as well as dynamic relations between changes in cytoskeletal structure and alterations in cell form and function.

NASA Discipline Number 40-20↗

Control of cytoskeletal mechanics by extracellular matrix, cell shape, and mechanical tension

We have investigated how extracellular matrix (ECM) alters the mechanical properties of the cytoskeleton (CSK). Mechanical stresses were applied to integrin receptors on the apical surfaces of adherent endothelial cells using RGD-coated ferromagnetic microbeads (5.5-microns diameter) in conjunction with a magnetic twisting device. Increasing the number of basal cell-ECM contacts by raising the fibronectin (FN) coating density from 10 to 500 ng/cm2 promoted cell spreading by fivefold and increased CSK stiffness, apparent viscosity, and permanent deformation all by more than twofold, as measured in response to maximal stress (40 dyne/cm2). When the applied stress was increased from 7 to 40 dyne/cm2, the stiffness and apparent viscosity of the CSK increased in parallel, although cell shape, ECM contacts, nor permanent deformation was altered. Application of the same stresses over a lower number ECM contacts using smaller beads (1.4-microns diameter) resulted in decreased CSK stiffness and apparent viscosity, confirming that this technique probes into the depth of the CSK and not just the cortical membrane. When magnetic measurements were carried out using cells whose membranes were disrupted and ATP stores depleted using saponin, CSK stiffness and apparent viscosity were found to rise by approximately 20%, whereas permanent deformation decreased by more than half. Addition of ATP (250 microM) under conditions that promote CSK tension generation in membrane-permeabilized cells resulted in decreases in CSK stiffness and apparent viscosity that could be detected within 2 min after ATP addition, before any measurable change in cell size.(ABSTRACT TRUNCATED AT 250 WORDS).

Non-NASA Center↗