A Hydrogen Peroxide Activatable Gemcitabine Prodrug for the Selective Treatment of Pancreatic Ductal Adenocarcinoma

The main concern in the use of anticancer chemotherapeutic drugs is host toxicity. Patients need to interrupt or change chemotherapy due to adverse effects. In this study, we aimed to decrease adverse events with gemcitabine (GEM) in the treatment of pancreatic ductal adenocarcinoma and focused on the difference of hydrogen peroxide levels in normal versus cancer cells. We designed and synthesized a novel boronate-ester-caged prodrug that is activated by the high H₂O₂ concentrations found in cancer cells to release GEM. An H₂O₂-activatable GEM (A-GEM) has higher selectivity for H₂O₂ over other reactive oxygen species (ROS) and cytotoxic effects corresponding to the H₂O₂ concentration in vitro. A xenograft model of immunodeficient mice indicated that the effect of A-GEM was not inferior to that of GEM when administered in vivo. In particular, myelosuppression was significantly decreased following A-GEM treatment compared with that following GEM treatment.     

Study on Dip Slope Failure at Higashi Takezawa Induced by 2004 Niigata-Ken Chuetsu Earthquake

An extensive number of slopes failed in the 2004 Niigata-ken Chuetsu Earthquake. Among them, a dip slope containing a weak layer in Yamakoshi Village (currently Nagaoka City) was investigated intensively. Regarding its morphological characteristics, it is argued that the earthquake reactivated a pre-existing failure plane which then formed most of the present sliding plane. In order to reveal the strength properties of the weak layer that formed the sliding plane, including the behavior against cyclic loading, a series of triaxial compression tests and simple shear tests was performed on undisturbed specimens that were retrieved by block sampling from the site. Based on the test results, a stability analysis and the calculation of the earthquake-induced displacement were performed. By extending Newmark's sliding block analysis, while considering the effects of the irregular geometry of the sliding plane and its strain-softening properties, a reasonable simulation of the process of this slope failure could be provided.     

Experimental investigation of flashback during start-up in practical premixed combustion

An experimental investigation of flashback was conducted during the start-up of a practical premixed kerosene burner. The flame propagations for normal ignition and flashback were visualized with high time-resolution. The timing of the fuel supply and ignition, as well as time sequence variations in pressures and temperatures in the burner, were analyzed to clarify the phenomena. The accumulated data revealed that flashback was caused by reverse flow of the hot combustion products through the flashback arrester and that the probability of flash back increased with increasing ignition delay, due to the higher pressures resulting from ignition and burning of the fuel accumulated in the combustion chamber during the delay. The thermal energy passing through the perforated plate used for flame quenching between the combustion chamber and the evaporating chamber was estimated using the reverse-flow pressures and their periods. The ignition energy estimated for the kerosene vapor mixtures was of the order of 10 mJ, which corresponds to the minimum ignition energy of other hydrocarbon fuels.     

Comparison of two possible routes of pathogen contamination of spinach leaves in a hydroponic cultivation system

The route of pathogen contamination (from roots versus from leaves) of spinach leaves was investigated with a hydroponic cultivation system. Three major bacterial pathogens, Escherichia coli O157:H7, Salmonella, and Listeria monocytogenes, were inoculated into the hydroponic solution, in which the spinach was grown to give concentrations of 10? and 103 CFU/ml. In parallel, the pathogens were inoculated onto the growing leaf surface by pipetting, to give concentrations of 10? and 103 CFU per leaf. Although contamination was observed at a high rate through the root system by the higher inoculum (10? CFU) for all the pathogens tested, the contamination was rare when the lower inoculum (103 CFU) was applied. In contrast, contamination through the leaf occurred at a very low rate, even when the inoculum level was high. For all the pathogens tested in the present study, the probability of contamination was promoted through the roots and with higher inoculum levels. The probability of contamination was analyzed with logistic regression. The logistic regression model showed that the odds ratio of contamination from the roots versus from the leaves was 6.93, which suggested that the risk of contamination from the roots was 6.93 times higher than the risk of contamination from the leaves. In addition, the risk of contamination by L. monocytogenes was about 0.3 times that of Salmonella enterica subsp. enterica serovars Typhimurium and Enteritidis and E. coli O157:H7. The results of the present study indicate that the principal route of pathogen contamination of growing spinach leaves in a hydroponic system is from the plant's roots, rather than from leaf contamination itself.     

Experimental and numerical analysis of multilayered steel sheets upon bending

In this study, the bending formability of multilayered steel sheets is evaluated by tensile tests, V-bending tests, and hemming tests. Enhanced formability was observed in these experiments, namely, the constituent high-strength materials were elongated beyond the original fracture strain limit. As a result of this effect, multilayered steel sheets were successfully formed in V-bending tests and even in hemming tests. Observations using a scanning electron microscope verified that no delamination occurred at interfaces. To represent the geometrical features of a multilayered steel sheet, a solid-element model under an isostrain condition was utilized in finite element modeling, where the rule of mixtures was adopted to obtain the flow curve of the constituent high-strength material, and a good agreement with experimental results was observed. Analyses using this finite element model were conducted to investigate the effect of the geometry on the springback of multilayered steel sheets undergoing V-bending.     

In situ observations and crystallographic analysis of martensitic transformation in steel

The development of a martensitic structure in a low-carbon and low-alloy steel was characterized using in situ confocal laser microscopy, high-speed photography and crystallographic analysis, including the nature of variant selection. The initial stage of transformation involves the partitioning of the austenite grain into packets, after which the rate of transformation is gradual. The crystallographic orientation of the plates that form is not random, but involves selection determined by the relationship between the shape deformation direction and the free surface. The vicinity of austenite grain and twin boundaries, and martensite/austenite interfaces also affect variant selection.     

A Novel Chemoenzymatic Synthesis of Sulfated Type 2 Tumor‐Associated Carbohydrate Antigens by Transglycosylation of Sulfated Lewis X Oxazoline Catalyzed by Keratanase II

Sulfated type 2 carbohydrate chains are known tumor‐associated carbohydrate antigens (TACAs). Many reports on cancer vaccines employing TACAs as specific antigens have been published, but structurally specified sulfated TACAs have not been used because of the low natural abundance and difficulties in chemical synthesis. We demonstrate for the first time the synthesis of the sulfated type 2 TACAs with an l ‐fucose branch by keratanase‐II‐catalyzed transglycosylation of the sulfated Lewis X (Galβ(1→4)[Fucα(1→3)]GlcNAc(6‐OSO₃^?); su‐Le^x) oxazoline derivative. Two keratanase IIs (from Bacillus sp. Ks36 and Bacillus circulans KsT202) efficiently catalyzed the transglycosylation reaction of the su‐Le^x oxazoline derivative, thereby giving the su‐Le^x dimer as the main product in good yields. Structural analysis of the oligomers confirmed exclusive formation of the β(1→3) glycosidic bond.