Cell Mechanical and Physiological Behavior in the Regime of Rapid Mechanical Compressions that Lead to Cell Volume Change

Cells respond to mechanical forces by deforming in accordance with viscoelastic solid behavior. Studies of microscale cell deformation observed by high speed video microscopy have elucidated a new cell behavior in which sufficiently rapid mechanical compression of cells can lead to transient cell volume loss and then recovery. This work has discovered that the resulting volume exchange between the cell interior and the surrounding fluid can be utilized for efficient, convective delivery of large macromolecules (2000 kDa) to the cell interior. However, many fundamental questions remain about this cell behavior, including the range of deformation time scales that result in cell volume loss and the physiological effects experienced by the cell. In this study, a relationship is established between cell viscoelastic properties and the inertial forces imposed on the cell that serves as a predictor of cell volume loss across human cell types. It is determined that cells maintain nuclear envelope integrity and demonstrate low protein loss after the volume exchange process. These results define a highly controlled cell volume exchange mechanism for intracellular delivery of large macromolecules that maintains cell viability and function for invaluable downstream research and clinical applications.     

Adhesion force approximation at varying consolidation stresses for fine powder under humid conditions

Interparticle adhesion forces in fine powders are greatly influenced by varying relative humidity (RH) conditions. The present study estimated the interparticle adhesion forces developed in corn starch powder under humid conditions at varying applied consolidation stresses using tensile strength determination approach. Shear test was used to determine tensile strength of powder at 1–9 kPa consolidation pressures and extrapolated values of tensile strength at zero stress were used for force estimation in non-consolidated powders. A strong dependence of interparticle adhesion force on consolidation and RH conditions was observed, mainly due to alteration in the number of adhesive contacts and contact area. The results indicated that, at low consolidation and high RH, capillary force is the prevailing force contributing to the total interparticle adhesion in contrast to higher consolidation conditions where load induced contact force plays a dominant role. Furthermore, for nonconsolidated samples, the adhesion forces registered a steep jump above 60% RH which was primarily attributed to dominance of the liquid bridge forces. Also, forces determined from tensile strength approach and those predicted theoretically, as a summation of individual forces, yielded a similar trend. Overall, a simple and effective approach for interparticle force estimation of consolidated as well as loosely packed powders under varying humidity conditions is presented here.     

Distribution, enrichment and principal component analysis for possible sources of naturally occurring and anthropogenic radionuclides in the agricultural soil of Punjab state, India

Enrichment factor (EF) of elements including geo-accumulation indices for soil quality and principal component analysis (PCA) were used to identify the contributions of the origin of sources in the studied area. Results of (40)K, (137)Cs, (238)U and (232)Th including their decay series isotopes in the agricultural soil of Mansa and Bathinda districts in the state of Punjab were presented and discussed. The measured mean radioactivity concentrations for (238)U, (232)Th and (40)K in the agricultural soil of the studied area differed from nationwide average crustal abundances by 51, 17 and 43 %, respectively. The sequence of the EFs of radionuclides in soil from the greatest to the least was found to be (238)U > (40)K > (226)Ra > (137)Cs > (232)Th > (228)Ra. Even though the enrichment of naturally occurring radionuclides was found to be higher, they remained to be in I(geo) class of '0', indicating that the soil is uncontaminated with respect to these radionuclides. Among non-metals, N showed the highest EF and belonged to I(geo) class of '2', indicating that soil is moderately contaminated due to intrusion of fertiliser. The resulting data set of elemental contents in soil was also interpreted by PCA, which facilitates identification of the different groups of correlated elements. The levels of the (40)K, (238)U and (232)Th radionuclides showed a significant positive correlation with each other, suggesting a similar origin of their geochemical sources and identical behaviour during transport in the soil system.     

Notch sensitivity of orthotropic solids: interaction of tensile and shear damage zones

The macroscopic tensile strength of a panel containing a centre-crack or a centre-hole is predicted, assuming the simultaneous activation of multiple cohesive zones. The panel is made from an orthotropic elastic solid, and the stress raiser has both a tensile cohesive zone ahead of its tip, and shear cohesive zones in an orthogonal direction in order to represent two simultaneous damage mechanisms. These cohesive zones allow for two modes of fracture: (i) crack extension by penetration, and (ii) splitting in an orthogonal direction. The sensitivity of macroscopic tensile strength and failure mode to the degree of orthotropy is explored. The role of notch acuity and notch size are assessed by comparing the response of the pre-crack to that of the circular hole. This study reveals the role of the relative strength and relative toughness of competing damage modes in dictating the macroscopic strength of a notched panel made from an orthotropic elastic solid. Universal failure mechanism maps are constructed for the pre-crack and hole for a wide range of material orthotropies. The maps are useful for predicting whether failure is by penetration or kinking. Case studies are developed to compare the predictions with observations taken from the literature for selected orthotropic solids. It is found that synergistic strengthening occurs: when failure is by crack penetration ahead of the stress raiser, the presence of shear plastic zones leads to an enhancement of macroscopic strength. In contrast, when failure is by crack kinking, the presence of a tensile plastic zone ahead of the stress raiser has only a mild effect upon the macroscopic strength.     

Effect of defect dipoles on the dielectric and electrical properties of Mn:K2Ti6O13 lead-free ceramics: EPR spectroscopy-cum-dielectric-spectroscopy

In this paper, we report the synthesis of Mn:K₂Ti₆O₁₃ lead-free ceramics in a monoclinic phase with microtubular surface morphology via high temperature solid-state reactions. EPR-spectroscopy, achieved at room temperature and at X-band frequencies, recognised Mn²⁺, Mn³⁺, and Mn⁴⁺ partial substitutions at Ti⁴⁺ lattice sites with dominating Mn²⁺ substitution, and identified ( \textFe_\textTi^￠ {\text{Fe}}_{\text{Ti}}^{\prime } – V_\textO ^·· V_{\text{O}}^{ \cdot \cdot } ) and ( \textMn_\textTi^￠￠ {\text{Mn}}_{\text{Ti}}^{\prime \prime } – V_\textO ^·· V_{\text{O}}^{ \cdot \cdot } ) defect associate dipoles exhibited in the low-field EPR signals which smeared with excessive doping due to augmented exchange interactions. These dipoles rendered diffusive nature to the ferroelectric-paraelectric type phase transitions recognized in the ε _r (T) plots. Space charges, dipole orientation, and electrical conduction cooperatively contributed to dielectric losses. The study also provides a select composition with x = 0.05 mol% doping, performing low loss with high dielectric permittivity useful for high-temperature applications. Conductivity data proposed a shift from electronic (hopping) conduction mechanism in the low-temperate region to ionic (intratunnel) conduction at high-temperatures. Whereas slight doping augmented a.c. conductivity due to increased spin-phonon interaction and commanding electron hopping conduction, heavy doping reduced it, attributed to shrinkage of tunnel space and trapping of conduction electrons.     

Identity of adenylyl cyclase isoform determines the rate of cell cycle progression in NIH 3T3 cells

Cell cycle progression is regulated by cAMP in several cell types. Cellular cAMP levels depend on the activity of different adenylyl cyclases (ACs), which have varied signal-receiving capabilities. The role of individual ACs in regulating proliferative responses was investigated. Native NIH 3T3 cells contain AC6, an isoform that is inhibited by a variety of signals. Proliferation of exogenous AC6-expressing cells was the same as in control cells. In contrast, expression of AC2, an isoform stimulated by protein kinase C (PKC), resulted in inhibition of cell cycle progression and increased doubling time. In AC2-expressing cells, platelet-derived growth factor (PDGF) elevated cAMP levels in a PKC-dependent manner. PDGF stimulation of mitogen-activated protein kinases 1 and 2 (MAPK 1,2), DNA synthesis, and cyclin D1 expression was reduced in AC2-expressing cells as compared with control cells. Dominant negative protein kinase A relieved the AC2 inhibition of PDGF-induced DNA synthesis. Expression of AC2 also blocked H-ras-induced transformation of NIH 3T3 cells. These observations indicate that, because AC2 is stimulated by PKC, it can be activated by PDGF concurrently with the stimulation of MAPK 1,2. The elevation in cAMP results in inhibition of signal flow from the PDGF receptor to MAPK 1,2 and a significant reduction in the proliferative response to PDGF. Thus, the molecular identity and signal receiving capability of the AC isoforms in a cell could be important for proliferative homeostasis.     

Controlled hidden markov models for dynamically adapting patch clamp experiment to estimate Nernst potential of single-ion channels

This paper presents novel kernel-based stochastic learning algorithms for controlling the kinetics of single-ion channels in a patch clamp experiment. The algorithms yield efficient estimates of the equilibrium (Nernst) potential of an ion channel. The equilibrium potential of an ion channel is the applied external potential difference required to maintain electrochemical equilibrium across the ion channel. The algorithm adaptively controls the exploration of the learning algorithm to achieve an optimal balance between exploration and exploitation. An important feature of the resulting algorithm is that it is guaranteed to minimize the experimental effort. We illustrate the efficiency of the algorithms for the experimentally determined current voltage curve of a bi-ionic single potassium ion channel.     

Brownian dynamics simulation for modeling ion permeation across bionanotubes

The principles underlying Brownian dynamics (BD), its statistical consistency, and algorithms for practical implementation are outlined here. The ability to compute current flow across ion channels confers a distinct advantage to BD simulations compared to other simulation techniques. Thus, two obvious applications of BD ion channels are in calculation of the current-voltage and current-concentration curves, which can be directly compared to the physiological measurements to assess the reliability of the model and predictive power of the method. We illustrate how BD simulations are used to unravel the permeation dynamics in two biological ion channels-the KcsA K/sup +/ channel and ClC Cl/sup -/ channel.     

Impact response of sandwich plates with a pyramidal lattice core

The ballistic performance edge clamped 304 stainless-steel sandwich panels has been measured by impacting the plates at mid-span with a spherical steel projectile whose impact velocity ranged from 250 to 1300 m s⁻¹. The sandwich plates comprised two identical face sheets and a pyramidal truss core: the diameter of the impacting spherical projectile was approximately half the 25 mm truss core cell size. The ballistic behavior has been compared with monolithic 304 stainless-steel plates of approximately equal areal mass and with high-strength aluminum alloy (6061-T6) sandwich panels of identical geometry. The ballistic performance is quantified in terms of the entry and exit projectile velocities while high-speed photography is used to investigate the dynamic deformation and failure mechanisms. The stainless-steel sandwich panels were found to have a much higher ballistic resistance than the 6061-T6 aluminum alloy panels on a per volume basis but the ballistic energy absorption of the aluminum structures was slightly higher on a per unit mass basis. The ballistic performance of the monolithic and sandwich panels is almost identical though the failure mechanics of these two types of structures are rather different. At high impact velocities, the monolithic plates fail by ductile hole enlargement. By contrast, only the proximal face sheet of the sandwich plate undergoes this type of failure. The distal face sheet fails by a petalling mode over the entire velocity range investigated here. Given the substantially higher blast resistance of sandwich plates compared to monolithic plates of equal mass, we conclude that sandwich plates display a potential to outperform monolithic plates in multi-functional applications that combine blast resistance and ballistic performance.