Numerical Simulation of Neck Propagation in Double Network Hydrogel

In this study, we at first employ a nonaffine polymer chains network model to account for the irreversible structural change during the deformation of DN gels. And then, a finite element model of the DN gels under simple tension is constructed. On the other hand, neck propagation is one kind of localized instability and there will be a local transfer of strain energy from one part of the model to neighboring parts. To solve such unstable quasi-static problem, an automatic mechanism provided by Abaqus/Standard is employed. The simulation results show that the nonaffine polymer chains network model together with the stablization algorithm for localized transformation of strain energy can be employed to reproduce the phenomenon of neck propagation in DN gels very well

A case of histoplasmosis Report 1. Cinical, mycological and pathological observations

In our country it has been believed that there is no histoplasmosis here in Japan. However, from the above clinical signs, radiological characteristics, laboratory tests, pathological and mycological examinations, and experimental findings, we believe this is the first case of histoplasmosis in Japan.</p

PRL3-zumab, a first-in-class humanized antibody for cancer therapy

Novel, tumor-specific drugs are urgently needed for a breakthrough in cancer therapy. Herein, we generated a first-in-class humanized antibody (PRL3-zumab) against PRL-3, an intracellular tumor-associated phosphatase upregulated in multiple human cancers, for unconventional cancer immunotherapies. We focused on gastric cancer (GC), wherein elevated PRL-3 mRNA levels significantly correlated with shortened overall survival of GC patients. PRL-3 protein was overexpressed in 85% of fresh-frozen clinical gastric tumor samples examined but not in patient-matched normal gastric tissues. Using human GC cell lines, we demonstrated that PRL3-zumab specifically blocked PRL-3(+), but not PRL-3(–), orthotopic gastric tumors. In this setting, PRL3-zumab had better therapeutic efficacy as a monotherapy, rather than simultaneous combination with 5-fluorouracil or 5-fluorouracil alone. PRL3-zumab could also prevent PRL-3(+) tumor recurrence. Mechanistically, we found that intracellular PRL-3 antigens could be externalized to become “extracellular oncotargets” that serve as bait for PRL3-zumab binding to potentially bridge and recruit immunocytes into tumor microenvironments for killing effects on cancer cells. In summary, our results document a comprehensive cancer therapeutic approach to specific antibody-targeted therapy against the PRL-3 oncotarget as a case study for developing antibodies against other intracellular targets in drug discovery

Epithelial-mesenchymal transition-converted tumor cells can induce T-cell apoptosis through upregulation of programmed death ligand 1 expression in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor, and it is urgently needed to develop novel therapeutic strategies including immunotherapy. In this study, we investigated the upregulation of the programmed death ligand 1 (PD-L1) due to epithelial-mesenchymal transition (EMT) in ESCC using an in vitro treatment system with the EMT inducer, glycogen synthase kinase (GSK)-3 inhibitor, and we also analyzed the correlation of EMT and PD-L1 expression in the clinical tumor samples of both tissue microarray (TMA) samples (n = 177) and whole tissue samples (n = 21). As a result, the inhibition of GSK-3β induces EMT phenotype with upregulated vimentin and downregulated E-cadherin as well as increased Snail and Zinc finger E box-binding homeobox (ZEB)-1 gene expression. Simultaneously, we showed that EMT-converted ESCC indicated the upregulation of PD-L1 at both protein (total and surface) and mRNA levels. Of importance, we showed that EMT-converted tumor cells have a capability to induce T-cell apoptosis to a greater extent in comparison to original epithelial type tumor cells. Furthermore, the immunohistochemical stains of ESCC showed that PD-L1 expression on tumor cells was positively correlated with EMT status in TMA samples (P = .0004) and whole tissue samples (P = .0029). In conclusion, our in vitro and in vivo study clearly demonstrated that PD-L1 expression was upregulated in mesenchymal type tumors of ESCC. These findings provide a strong rationale for the clinical use of anti-PD- 1/ anti-PD- L1 monoclonal antibodies for advanced ESCC patients

Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine on psychomotor function and histamine-induced wheal- and flare-responses: a randomized double-blind, placebo-controlled study in healthy volunteers

Since most first-generation antihistamines have undesirable sedative effects on the central nervous systems (CNS), newer (second-generation) antihistamines have been developed to improve patients’ quality of life. However, there are few reports that directly compare the antihistaminic efficacy and impairment of psychomotor functions. We designed a double-blind, placebo controlled, crossover study to concurrently compare the clinical effectiveness of promethazine, a first-generation antihistamine, and fexofenadine and olopatadine, second-generation antihistamines, by measuring their potency as peripheral inhibitors of histamine-induced wheal and flare. Further, we investigated their sedative effects on the CNS using a battery of psychomotor tests. When single therapeutic doses of fexofenadine (60 mg), olopatadine (5 mg) and promethazine (25 mg) were given in a double-blind manner to 24 healthy volunteers, all antihistamines produced a significant reduction in the wheal and flare responses induced by histamine. In the comparison among antihistamines, olopatadine showed a rapid inhibitory effect compared with fexofenadine and promethazine, and had a potent effect compared with promethazine. In a battery of psychomotor assessments using critical flicker fusion, choice reaction time, compensatory tracking, rapid visual information processing and a line analogue rating scale as a subjective assessment of sedation, promethazine significantly impaired psychomotor function. Fexofenadine and olopatadine had no significant effect in any of the psychomotor tests. Promethazine, fexofenadine and olopatadine did not affect behavioral activity, as measured by wrist actigraphy. These results suggest that olopatadine at a therapeutic dose has greater antihistaminergic activity than promethazine, and olopatadine and fexofenadine did not cause cognitive or psychomotor impairment

Arc-plasma Reduction of Vanadium Oxide with Carbon

The reduction of vanadium pentoxide by carbon has been investigated in an argon plasma-arc furnace. Briquettes of vanadium pentoxide and carbon mixtures have been examined and the results are as follows : 1) The optimum mixing ratio of carbon and vanadium pentoxide, C/V_2O_5, is approximately 4.5 and is smaller than the stoichiometric ratio of 5. When the mixing ratio is less than 4.5, the oxygen remaining in the product increases, while the vanadium carbide content increases when the ratio is greater than 5. 2) The sample is fused within 45 seconds by the plasma-arc and the reduction of vanadium oxide proceeds rapidly to nearly 90% vanadium content in the melt. Subsequent reduction in the molten state is slow. Within 10 minutes the vanadium content reaches a maximum of 96%. 3) Preliminary sintering of the briquette results in good recovery of vanadium due to the diminished loss of the sample under the plasma flame. 4) An increase of the vanadium content is not observed as temperature is increased from 2100 to 2800℃. 5) The hardness of the product with the highest vanadium content is about H_V 290 and is much larger than that of vanadium metal due to the small amount of remaining oxygen and/or carbon. 6) By means of EPMA, it is observed that the well developed, dendritic, primary crystals contain a small amount of carbon and oxygen in solid solution is observed. In this study, a vanadium metal of 96% purity has been produced within 10 minutes in spite of the strong affinity of vanadium for carbon or oxygen

Arc-plasma Reduction of Tantalum Oxide with Carbon

Metallic tantalum is one of the prominent refractory and corrosion-resistant metals. By the conventional production processes, however, tantalum metal powder is produced because of its high melting temperature. The plasma-arc furnace provides a stable high temperature. In this work, the carbon reduction of tantalum pentoxide has been investigated in a plasma-arc furnace. The sample is a mixture of tantalum pentoxide and graphite, vacuum pressed into a briquette and has been reduced at about 3100℃. Argon has been used as the arc gas. The optimum mixing ratio of carbon and tantalum pentoxide, C/Ta_2O_5 is 5.10?5.15. The sample, weighing 7 g is fused within 60?70 seconds by plasma-arc heating and the reduction of molten tantalum oxide with solid carbon proceeds rapidly to approximately 99.5 % Ta during this period. The reduction that follows in the molten state is slow. Within about 10 minutes, the maximum tantalum content of the massive metal product reaches 99.9 % and the oxygen and carbon remaining in the product are 50 ppm and 400?500 ppm respectively