Reconstructive surgery for ischemic-type lesions at the bile duct bifurcation after liver transplantation

Cholestatic liver injury appears to result from the induction of hepatocyte apoptosis by toxic bile salts such as glycochenodeoxycholate (GCDC). Previous studies from this laboratory indicate that cathepsin B is a downstream effector protease during the hepatocyte apoptotic process. Because caspases can initiate apoptosis, the present studies were undertaken to determine the role of caspases in cathepsin B activation. Immunoblotting of GCDC-treated McNtcp.24 hepatoma cells demonstrated cleavage of poly(ADP-ribose) polymerase and lamin B1 to fragments that indicate activation of effector caspases. Transfection with CrmA, an inhibitor of caspase 8, prevented GCDC-induced cathepsin B activation and apoptosis. Consistent with these results, an increase in caspase 8-like activity was observed in GCDC-treated cells. Examination of the mechanism of GCDC-induced caspase 8 activation revealed that dominant-negative FADD inhibited apoptosis and that hepatocytes isolated from Fas-deficient lymphoproliferative mice were resistant to GCDC-induced apoptosis. After GCDC treatment, immunoprecipitation experiments demonstrated Fas oligomerization, and confocal microscopy demonstrated DeltaFADD-GFP (Fas-associated death domain-green fluorescent protein, aggregation in the absence of detectable Fas ligand mRNA. Collectively, these data suggest that GCDC-induced hepatocyte apoptosis involves ligand-independent oligomerization of Fas, recruitment of FADD, activation of caspase 8, and subsequent activation of effector proteases, including downstream caspases and cathepsin B.     

Severe Plastic Deformation as a Means of Producing Ultra-Fine-Grained Net-Shaped Micro Electro-Mechanical Systems Parts

It is proposed to use a miniaturized version of equal channel angular pressing (ECAP) as a means of producing micro electro-mechanical systems (MEMS) parts. The benefits of such a processing technique are the possibility to reach the desired grain refinement down to the micron scale and to enhance the strength of the material at the same time. The viability of this concept is confirmed by the results obtained by transmission electron microscopy and microhardness testing of Al specimens. An integrated process with two ECAP passes and a final extrusion step is also discussed. Finite element simulations suggest that the strains reached in this process are sufficient for the material to attain superplastic behavior, thus reducing the load on the tooling and enhancing the feasibility of MEMS part manufacturing. This article is based on a presentation made in the symposium entitled “Ultrafine-Grained Materials: from Basics to Application,” which was held on September 25–27, 2006 in Kloster Irsee, Germany.     

Perspectives on ‘personal identity’

‘Identity’ is a problematic concept, and relates to other difficult concepts, such as ‘the person’. It is also a problematic public issue in the activities and relationships in which states, businesses, and the public engage. These involve questions of data protection and privacy, as well as of surveillance and categorisation. This paper takes a look at these matters by way of an overview that may afford insights for further investigation and debate. While it is not specifically oriented towards technological issues, technologies that are in use or being developed for identity management have a bearing on the question of personal identity and identification.     

Endoglin modulates cellular responses to TGF-beta 1

Endoglin is a homodimeric membrane glycoprotein which can bind the beta 1 and beta 3 isoforms of transforming growth factor-beta (TGF-beta). We reported previously that endoglin is upregulated during monocyte differentiation. We have now observed that TGF-beta itself can stimulate the expression of endoglin in cultured human monocytes and in the U-937 monocytic line. To study the functional role of endoglin, stable transfectants of U-937 cells were generated which overexpress L- or S- endoglin isoforms, differing in their cytoplasmic domain. Inhibition of cellular proliferation and downregulation of c-myc mRNA which are normally induced by TGF-beta 1 in U-937 cells were totally abrogated in L-endoglin transfectants and much reduced in the S-endoglin transfectants. Inhibition of proliferation by TGF-beta 2 was not altered in the transfectants, in agreement with the isoform specificity of endoglin. Additional responses of U-937 cells to TGF-beta 1, including stimulation of fibronectin synthesis, cellular adhesion, platelet/endothelial cell adhesion molecule 1 (PECAM-1) phosphorylation, and homotypic aggregation were also inhibited in the endoglin transfectants. However, modulation of integrin and PECAM-1 levels and stimulation of mRNA levels for TGF-beta 1 and its receptors R-I, R-II, and betaglycan occurred normally in the endoglin transfectants. No changes in total ligand binding were observed in L-endoglin transfectants relative to mock, while a 1.5-fold increase was seen in S-endoglin transfectants. The degradation rate of the ligand was the same in all transfectants. Elucidating the mechanism by which endoglin modulates several cellular responses to TGF-beta 1 without interfering with ligand binding or degradation should increase our understanding of the complex pathways which mediate the effects of this factor.     

Light scattering by optically heterogeneous polymer systems: stress whitening in polypropylene materials

Summary A theoretical background is presented which allows the assessment of the physical nature of turbidity in heterogeneous polymeric materials. The theory (based on the diffusion approximation of the transfer theory and Kubelka-Munk theory) predicts a decreasing spectral dependence of turbidity with increasing wavelength for a matrix with embedded particles of slightly different refractive indices, but a flat dependence of this quantity for a matrix material with microvoids. It is demonstrated that the diffuse reflectance displays the same type of wavelength dependence for the thick layer approximation. Indeed, diffuse light reflectance experiments on bulk specimens using an integrating sphere accessory reveal the first type of behaviour for nondeformed neat and rubber-modified polypropylenes. On the other hand, the second type of behaviour was observed with stress-whitened neat and rubber-modified polypropylenes after solid-state drawing.     

Block-decoded sense-amplifier driver for high-speed sensing inDRAM's

Safe sensing of the weak cell signal in DRAMs with low sense signals and fast sensing with low peak currents, both important design demands in 64- and 256-Mb DRAM development, are addressed. A block-decoded sense-amplifier driver concept is proposed. Optimized trigger pulse shapes are formed with local driver circuits to achieve high sensing safety at the beginning of the sensing period as well as fast amplification in the cell block containing the addressed memory cell. The nonaddressed blocks are triggered more slowly to reduce the peak current. Thus, reliable sensing of small initial sense signals is obtained in the shortest possible time, while the total current is kept small. As an example, for a 16-Mb DRAM, the sensing time-and hence the access time-can be reduced by at least 5 ns and is about 50% of the conventional sensing time     

Class-F power amplifiers with maximally flat waveforms

Class-F power amplifiers (PA's) employ harmonic-frequency resonators to shape their drain or collector waveforms to improve efficiency. Generally, the output network must present the drain with either an open or short circuit at the harmonic frequencies. At VHF and higher frequencies, the drain capacitance, lead inductance, lead length, and dispersion make implementation of reasonably ideal tuned circuits difficult. However it is possible to control the impedances at a finite number of harmonics. This note first derives the basic relationships among the Fourier coefficients of the waveforms and the performance of the amplifier. Fourier coefficients for maximally flat waveforms are then derived for inclusion of up to the fifth harmonic. Amplifier performance is then tabulated as a function of which harmonics are included in the voltage and current waveforms. Efficiency increases from 50% of class A toward 100% as harmonics are added. Power-output capability increases by up to 27%