Generation of metastatic variants of Eker renal carcinoma cell lines for experimental investigation of renal cancer metastasis

We and others have demonstrated that a mutation in Tsc2 is the rate-limiting step for renal carcinogenesis in the Eker rat model. Although inactivation of Tsc2 results in development of renal tumors, it is not sufficient for metastatic renal cell carcinomas (RCs) in the Eker rat. To investigate the additional genetic event(s) necessary for cancer metastasis, we have established highly metastatic S-Lk9d-SLM cell lines from a non-metastatic RC cell line (Lk9dL) by co-implantation with a foreign body (gelatin sponge). Since these cell lines were remarkably different in metastatic performance (all and none, respectively) despite having the same genetic background, they should be useful experimental tools to investigate metastasis-promoting events in renal carcinogenesis.     

Analysis for optimum threshold voltage and load current of E-D-type GaAs DCFL circuits

A GaAs MESFET E-D invertor was analysed to estimate the optimum threshold voltage VT for a switching FET, and the optimum load current IL for a load FET, that will minimise the invertor switching time. The calculated results show that the optimum VT lies at around 0.2 V, and the optimum IL is about 55% of the saturation current of the switching FET.     

The high performance liquid chromatographic determination of total malondialdehyde in vegetable oil with dansyl hydrazine

A simple high-performance liquid chromatographic (h.p.l.c.) method has been developed for determining total malondialdehyde (MDA), including free MDA and MDA released from its precursor in vegetable oils. Free MDA was reacted with dansyl hydrazine in an acidic medium, and the product, 1-dansyl-pyrazole(DP), was determined by h.p.l.c. The reaction releasing MDA from its precursor requires Fe³⁺ in 5% hydrochloric acid medium. Recoveries of free MDA and tetramethoxypropane (used as an MDA precursor) in vegetable oils were satisfactory. During autoxidation, a remarkable difference between the DP values of methyl oleate, methyl linoleate and some vegetable oils, and that of methyl linolenate was observed. Only methyl linolenate released MDA during autoxidation. For autoxidised methyl linolenate the DP value correlated with the thiobarbituric acid(TBA) value, although the DP value was only 30% of the TBA value.     

Drift Collection Calorimetry Using a Combined Radiator and Field Shaping Structure of Lead Glass Tubing

A design for a drift collection calorimeter having a combined radiator and electric field shaping structure made of fused lead glass tubing is described. Reduction of a surface layer of lead oxide in a hydrogen oven is used to form a high resistance metallic layer on the interior of the tubes. This layer is used as a continuous voltage divider for drift field shaping. The EGS shower Monte Carlo code was used to model the performance of the proposed calorimeter. The effects of choice of the tube geometry, gas pressure and sampling scheme (digital vs. conventional) are discussed. The possibility of using this type of radiator/drift field structure in liquid argon is briefly considered.     

A finite element method for contact problems related to fracture mechanics

A finite element method for contact problems in crack mechanics is developed on the basis of the penalty function method. The method is successfully applied to three important problems in fracture mechanics: a crack propagated from a pin hole, a two-point supported specimen with an edge crack loaded by a stamp, and a thick plate with a through-wall crack under bending force.     

“Click Peptide“: pH‐Triggered in Situ Production and Aggregation of Monomer Aβ1–42

Into neutral : We demonstrate the unique features of a pH click peptide based on an O‐acyl isopeptide method. Under acidic conditions, the click peptide remains in a monomeric form. Upon increase of the pH to 7.4, the click peptide is quickly able to convert into Aβ1–42 through an O‐to‐N intramolecular acyl migration. Further study using this pH click peptide would elucidate the pathological role of Aβ1–42 in Alzheimer's disease.

     

Excess estrogen sulfoconjugation as the possible cause for a poor sign of parturition in pregnant cows carrying somatic cell clone fetuses

We conducted this study to elucidate a factor causing a poor sign of parturition and prolonged gestation, which is frequently observed in cows carrying somatic clone fetuses. Pre-partum rises in concentrations of plasma estrone and estradiol-17beta in the recipient cows pregnant with clones were subtle. By contrast, the plasma concentration of estrone sulfate in clone pregnancies increased gradually from pre-initiation of parturition induction whereas control cows that received in vivo-derived embryos showed a significant increase at parturition. Therefore, in clone pregnancies, the ratio of estrone/estrone sulfate was low during the pre-partum period compared with control. Messenger RNA expression of estrogen sulfotransferase (SULT1E1) in the placenta at parturition was significantly higher in clone pregnancies than control pregnancies and was localized in binucleate cells (BNC). SULT1E1 mRNA abundance was negatively and positively correlated with concentrations of maternal estrone and estrone sulfate at parturition respectively. Messenger RNA expressions of estrogen sulfatase (STS) and aromatase (CYP19) were similar between clone and control pregnancies and were localized in BNC and caruncular epithelial cells. STS and CYP19 mRNA abundances showed positive correlations with maternal estradiol-17beta concentration. The population of BNC in the placenta did not differ between clone and control pregnancies. Plasma cortisol concentration of vaginally delivered newborn clone calves was comparable with those of control, although cesarean section delivered clone calves showed a low concentration. These results suggest that excess estrogen sulfoconjugation is the reason for the perturbed low ratio of active to inactive estrogens and the resulting hormonal imbalance contributes to the lack of overt signs of readiness for parturition in cows pregnant with clones.     

A New Lead Identification Strategy: Screening an sp3-rich and Lead-like Compound Library Composed of 7-Azanorbornane Derivatives

Although the advantages of sp³-rich, sterically complicated molecules in drug development have been pointed out, modern screening libraries are filled with planar, sp²-rich components. Compounds that are sp³-rich are difficult to synthesize, and thus we aimed to invent an efficient method to construct sp³-rich libraries. By modifying sp³-rich 7-azanorbornane scaffolds through click chemistry, we efficiently prepared a small set of compounds. These compounds were not only sp³-rich, but also had sufficient “lead-like” properties in view of molecular weights and hydrophobicity. Screening assays of this library provided weak κ opioid receptor agonists and growth hormone secretagogue receptor agonists with high hit rates. These results indicate that the 7-azanorbornane scaffold may be a “privileged structure” for lead identification in drug discovery.     

Konzept einer autarken elektrischen und thermischen Energieversorgung auf Basis von Photovoltaik

A photovoltaic system could supply a single-family house with electrical power, warm water, and room heat if the energy would be distributed over the year to suit the load profile. However, storage systems for this are not state of the art yet. A concrete example is used to estimate which parameters such a power storage system should have. A suitable electrochemical reaction system based on inorganic salt mixtures is proposed. The German Federal Ministry of Education and Research is currently funding the development of a world storage facility based on the same reaction system.     

Functional Characterization of 3-Aminobenzoic Acid Adenylation Enzyme PctU and UDP-N-Acetyl-d-Glucosamine: 3-Aminobenzoyl-ACP Glycosyltransferase PctL in Pactamycin Biosynthesis

Pactamycin is an antibiotic produced by Streptomyces pactum with antitumor and antimalarial properties. Pactamycin has a unique aminocyclitol core that is decorated with 3-aminoacetophenone, 6-methylsaliciate, and an N,N-dimethylcarbamoyl group. Herein, we show that the adenylation enzyme PctU activates 3-aminobenzoic acid (3ABA) with adenosine triphosphate and ligates it to the holo form of the discrete acyl carrier protein PctK to yield 3ABA-PctK. Then, 3ABA-PctK is N-glycosylated with uridine diphosphate-N-acetyl-d -glucosamine (UDP-GlcNAc) by the glycosyltransferase PctL to yield GlcNAc-3ABA-PctK. Because 3ABA is known to be a precursor of the 3-aminoacetophenone moiety, PctU appears to be a gatekeeper that selects the appropriate 3-aminobenzoate starter unit. Overall, we propose that acyl carrier protein-bound glycosylated 3ABA derivatives are biosynthetic intermediates of pactamycin biosynthesis.