Liver cell therapy: is this the end of the beginning?

The prevalence of liver diseases is increasing globally. Orthotopic liver transplantation is widely used to treat liver disease upon organ failure. The complexity of this procedure and finite numbers of healthy organ donors have prompted research into alternative therapeutic options to treat liver disease. This includes the transplantation of liver cells to promote regeneration. While successful, the routine supply of good quality human liver cells is limited. Therefore, renewable and scalable sources of these cells are sought. Liver progenitor and pluripotent stem cells offer potential cell sources that could be used clinically. This review discusses recent approaches in liver cell transplantation and requirements to improve the process, with the ultimate goal being efficient organ regeneration. We also discuss the potential off-target effects of cell-based therapies, and the advantages and drawbacks of current pre-clinical animal models used to study organ senescence, repopulation and regeneration.     

The diterpenoid alkaloid noroxoaconitine is a Mapkap kinase 5 (MK5/PRAK) inhibitor

The mitogen-activated protein kinase-activated protein kinase MK5 is ubiquitously expressed in vertebrates and is implicated in cell proliferation, cytoskeletal remodeling, and anxiety behavior. This makes MK5 an attractive drug target. We tested several diterpenoid alkaloids for their ability to suppress MK5 kinase activity. We identified noroxoaconitine as an ATP competitor that inhibited the catalytic activity of MK5 in vitro (IC₅₀ = 37.5 μM; K _i = 0.675 μM) and prevented PKA-induced nuclear export of MK5, a process that depends on kinase active MK5. MK5 is closely related to MK2 and MK3, and noroxoaconitine inhibited MK3- and MK5- but not MK2-mediated phosphorylation of the common substrate Hsp27. Molecular docking of noroxoaconitine into the ATP binding sites indicated that noroxoaconitine binds more strongly to MK5 than to MK3. Noroxoaconitine and derivatives may help in elucidating the precise biological functions of MK5 and may prove to have therapeutic values.     

Generation of sodium hypochlorite (NaOCl) from sodium chloride solution using C/PbO2 and Pb/PbO2 electrodes

Two modified electrodes (Pb/PbO₂ and C/PbO₂) were prepared by electrodepositing a lead oxide layer on lead and carbon substrates. These modified electrodes were used as anodes for the generation of sodium hypochlorite (NaOCl) from sodium chloride solution. Different operating conditions and factors affecting the treatment process of NaOCl generation, including current density, pH values, conductive electrolytes, and electrolysis time, were studied and optimized. By comparison the C/PbO₂ electrode shows a higher efficiency than the Pb/PbO₂ electrode for the generation of NaOCl.     

Photocatalytic degradation of methylene blue by nanostructured Fe/FeS powder under visible light

The photocatalytic performance of mechano-thermally synthesized Fe/FeS nanostructures formed from micron-sized starting materials was compared with that of a thermally synthesized nanostructure with nano-sized precursors in this paper. The properties of as-synthesized materials were studied by X-ray diffraction (XRD), transmission electron microscopy (TEM), vibrating sample magnetometry (VSM), diffuse reflectance spectroscopy (DRS), and ultraviolet-visible (UV-Vis) spectroscopy. The effects of irradiation time, methylene blue (MB) concentration, catalyst dosage, and pH value upon the degradation of MB were studied. Magnetic properties of the samples showed that both as-synthesized Fe/FeS photocatalysts are magnetically recoverable, eliminating the need for conventional filtration steps. Degradation of 5 ppm of the MB solution by mechano-thermally synthesized Fe/FeS with a photocatalyst dosage of 1 kg/m3 at pH 11 can reach 96% after 12 ks irradiation under visible light. The photocatalytic efficiency is higher in alkaline solution. The kinetics of photocatalytic degradation in both samples is controlled by a first-order reaction. However, the rate-constant value in the thermally synthesized Fe/FeS photocatalyst sample is only 1.5 times greater than that of the mechano-thermally synthesized one.     

Identification of functional genes during Fas-mediated apoptosis using a randomly fragmented cDNA library

We describe a general strategy for the identification of functional genes that, when downregulated, result in a selectable phenotype. This strategy is based on expression selection of cDNA fragments that counteract their cognate genes. A cDNA library containing random fragments expressed in human HepG2, A375 and CLS-354 cells was used to identify functional genes whose inhibition conferred resistance to Fas-induced apoptosis. Thirty-five clones were isolated, 28 of which were derived from unknown genes, that tagged 19 individual genes and 7 of which referred to known genes that tagged the apoptosis-related protein (APR)-1, -2 and indoleamine-pyrrole 2,3,-dioxygenase (IDO). The ability of APR-1-, -2- and IDO-derived antisense RNAs to induce resistance to Fas in HepG2, A375 and CLS-354 cells suggested that APR-1, -2 and IDO genes are involved in the machinery of Fas-mediated apoptosis. Our gene discovery strategy provides a generally applicable procedure to identify functional genes that interfere with apoptosis, and may therefore be clinically relevant for tumor therapy.Received 28 April 2005; received after revision 20 June 2005; accepted 5 July 2005     

Design Knowledge and Software Engineering

This paper points out various relationships between Design Knowledge and Software Engineering. After introduction of human design, the relationships between industrial Software Engineering is discussed, then further details of human design knowledge are revealed with discussions on humanistic aspects of design.     

与删除卷积码相结合的非均匀16-DAPSK在无线广播信道上的性能

导出了加性高斯白噪声和Rayleigh衰落信道上非均匀16-DAPSK错误概率的简单闭合表达式.对于多媒体通信和组播传输而言,非均匀16-DAPSK是有用的.给出了带有删除卷积编码的非均匀16-DAPSK调制的性能.结果表明卷积编码可与非均匀16-DAPSK调制用于在无线电广播系统中传输附加消息,而对于基本消息几乎没有损伤.     

伊朗食虫虻（双翅目：食虫虻科）的猎物记录

本文根据伊朗食虫虻科AsiLidae的文献资料，记录了伊朗104种食虫虻的130种猎物。这些猎物隶属昆虫纲Insecta的7个目（膜翅目Hymenoptera，双翅目Diptera，鞘翅目CoLeoptera，直翅目Orthoptera，鳞翅目Lepidoptera，半翅目异翅亚目Heteroptera和脉翅目Neuroptera）37科，此外，还有1种蜘蛛也是食虫虻的猎物。