Direct monitoring of the calcium concentration in the sarcoplasmic and endoplasmic reticulum of skeletal muscle myotubes

Direct monitoring of the free Ca2+ concentration in the sarcoplasmic reticulum (SR) was carried out in rat skeletal myotubes transfected with a specifically targeted aequorin chimera (srAEQ). Myotubes were also transfected with a chimeric aequorin (erAEQ) that we have demonstrated previously is retained in the endoplasmic reticulum (ER). Immunolocalization analysis showed that although both recombinant proteins are distributed in an endomembrane network identifiable with immature SR, the erAEQ protein was retained also in the perinuclear membrane. The difficulty of measuring [Ca2+] in 100-1000 microM range was overcome with the use of the synthetic coelenterazine analogue, coelenterazine n. We demonstrate that the steady state levels of [Ca2+] measured with srAEQ is around 300 microM, whereas that measured with erAEQ is significantly lower, i.e. around 200 microM. The effects of caffeine, high KCl, and nicotinic receptor stimulation, in the presence or absence of external calcium or after blockade of the Ca-ATPase, were investigated with both chimeras. The kinetics of [Ca2+] changes revealed by the erAEQ were similar, but not identical, neither quantitatively nor qualitatively, to those monitored with the srAEQ, indicating that at this stage of muscle development, differences exist between SR and ER in their mechanisms of Ca2+ handling. The functional implications of these findings are discussed.     

Efficacy of lonidamine combined with different DNA-damaging agents in the treatment of the MX-1 tumor xenograft

The a.c. conductivity of the proteins lysozyme and subtilisin, both in their active and inactive or inhibited forms were determined theoretically. For this, quantum mechanical calculations and a random walk theory were used. The conclusions are that these enzymatic proteins can easily transport electrons which is most probably important in their role as catalysators of biochemical reactions. The electron transport is sensitive to three-dimensional changes of the active sites of these enzymes which have more flexibility than the whole molecule. Therefore, the flexibility of the active sites of enzyme catalysts is not only important for the conformational fitting with the reactants, but also strongly influences the transport in biochemical reactions.     

Salvage chemotherapy with mitomycin, vindesine, and cisplatin (MiViP) in recurrent carcinoma of the cervix

We report two cases of metastatic non-functioning pancreatic endocrine tumour with very elevated plasma levels of alpha-fetoprotein. In these two cases, serial plasma levels of alpha-fetoprotein, initially normal, correlated well with hepatic tumour progression and were associated with fatal outcome. These results suggest that elevated plasma concentration of alpha-fetoprotein may be caused by metastatic pancreatic endocrine tumour and than alpha-fetoprotein serial measurement may be useful in prognostic evaluation.     

Diffusion bonding of an aluminium-lithium alloy (AA8090) using aluminium-copper alloy interlayers

Diffusion bonds have been produced between sheets of an Al-Li-Cu-Mg-Zr alloy using aluminium-4% copper vapour deposited metallic interlayers. Microstructural changes occurred both in the parent alloy and in the bond interface after diffusion bonding cycles and post-bonding heat treatments were analysed. Different metallographic techniques (light microscopy, scanning and transmission electron microscopy) have been used. Diffusion bonding trials were carried out using the same alloy (AA8090), both in non-superplastic (T6) and superplastic conditions. Differences in their behaviours in relation to diffusion bonding were observed.     

The geometric nature of plasticity laws

This paper concerns the plasticity constitutive laws in small strain. In the thermodynamic approach developed here, the key concept is that of internal variables. The differential nature of plasticity law has been pointed out for a long time. If we unite the invariance condition of these laws in a state variable transformation, this involves, ultimately, that the natural mathematic frame of plasticity theory is Differential Geometry. The system state is defined as a point of a differentiable manifold. The state variable are the local coordinates of this point in a chart. The internal stresses are the components of a covariant vector of the cotangent bundle to internal state manifold and the elastic domain is a convex part of cotangent vector space. The plastic yield criteria such as von Mises condition define a Riemannian structure over the manifold. The metric element is identified with the internal dissipation element. Constitutive laws link the covariant derivatives of the thermodynamic stress with the state variable. Hardening modulus splits up in two parts, kinematic hardening and metric hardening. This last is defined by Christoffel connection coefficients. Applied to von Mises isotropic yield condition, the metric hardening is identified with isotropic hardening. The Baltov-Sawczuk model is also analysed. The use of appropriate polar coordinates simplifies significantly the computations. Generalization to a significant category of non-differentiable yield criteria, such as Tresca condition, is considered by introducting a metric tensor family. The adaptation of Drucker's postulate to the proposed model requires the introduction of parallel transport of the internal stress covector. Generally, this transport is different over distinctive paths joining two points. This fact expresses internal state manifold curvature. The Riemann-Christoffel tensor is computed for von Mises, Baltov-Sawczuk and Tresca models.     

On-body propagation velocity estimation using ultra-wideband frequency-domain spatial correlation analyses

On-body communications around the human torso are considered, using ultra-wideband transmissions. The velocity of the diffracted wave propagating around the body is extracted from frequency- domain spatial correlation analyses.     

Characterization of an ASIC for CPG sensors with grid-only depth of interaction sensing

A new version of the front-end application specific integrated circuit (ASIC) for co-planar-grid (CPG) sensors is presented. Compared to the first version, the ASIC is optimized for signal/noise performance, modified in peaking time, and it implements timing signals to measure the depth of interaction using the grids signals only. Experimental results using state-of the-art CPG sensors and different approaches for reducing the error due to electron trapping are reported. A new technique that makes use of the sum and difference of the grids signals is also presented.     

Detection of failure sites by focused ion beam and nano-probing in the interconnect of three-dimensional stacked circuit structures

Focused ion beam (FIB) and nano-probing were applied for failure analysis of three-dimensional stacked circuits with copper through-silicon-vias between the stacked chips. The failure analysis was done after high temperature storage and thermal cycling tests. Passive voltage contrast in FIB allowed to pinpoint the open sites. FIB cross-sections showed the presence of opens at the bottom of the copper vias. The failure cause was suspected to be an interlayer particle, which was confirmed by optical profilometry. Nano-probing was used on another sample to pinpoint the failure location through the measurement of the local resistance within the daisy chains. The failure was traced out to be related with surface contamination.