Analyzing and simulating supply chain disruptions to the automobile industry based on experiences of the Great East Japan Earthquake

The Great East Japan Earthquake revealed serious weaknesses in the supply chain management (SCM) employed by Japanese industries, and particularly by the automobile industry. Observed supply chain disruptions and production line shutdowns are recognized as symbolic of weaknesses in industrial SCM. The Japanese automobile industry in particular is now keen to improve supply chain resiliency in terms of automobile assembly line continuity. In view of this, we i) review observed negative impacts of the Great East Japan Earthquake on the automobile industry, ii) identify current strategies being evaluated by the automobile industry for improving supply chain resiliency, iii) develop a numerical supply chain model for the automobile industry, and iv) evaluate efforts to improve SCM practice through inclusion of risk mitigation measures. We conclude with recommendations for policy development to further strengthen automobile industry resiliency

前立腺癌における血清γ-セミノプロティンの測定

前立腺癌の新しいマーカーとして, γ-セミノプロテイン(γ-Sm)と前立腺性酸性ホスファターゼ(PAP)とを比較評価した.未治療前立腺癌におけるγ-SMおよびPAPのsensitivityは, それぞれ81%, 67%であった.γ-Smはすべての病期で前立腺肥大症と比較して陽性率が高かった.前立腺癌ではγ-SmとPAPは相関を示さなかった.γ-SmとPAPを同時に測定することにより, 感度が上昇した.γ-SmおよびPAPのspecificityはそれぞれ87%と90%であった.内分泌療法を施行した病期D2において, γ-SmはPAPよりもより多く正常化した.以上より, γ-Smは前立腺癌のもう1つの有用なマーカーであるといえるSerum gamma-seminoprotein (gamma-Sm) was evaluated as a new marker for prostatic cancer in comparison with prostatic acid phosphatase (PAP). The sensitivity of gamma-Sm and PAP for untreated prostatic cancer was 81% and 67%, respectively. gamma-Sm showed a higher positive rate over all stages than in benign prostatic hypertrophy (BPH). There was no correlation between gamma-Sm and PAP in prostatic cancer. Improved sensitivity was obtained by simultaneous measurement of gamma-Sm and PAP. Specificity of gamma-Sm and PAP for BPH was 87% and 90%, respectively. gamma-Sm normalized after endocrine therapy for stage D2 more often than did PAP. These results indicate that gamma-Sm is another useful marker to evaluate prostatic cancer

The Shigella OspC3 Effector Inhibits Caspase-4, Antagonizes Inflammatory Cell Death, and Promotes Epithelial Infection

SummaryCaspase-mediated inflammatory cell death acts as an intrinsic defense mechanism against infection. Bacterial pathogens deploy countermeasures against inflammatory cell death, but the mechanisms by which they do this remain largely unclear. In a screen for Shigella flexneri effectors that regulate cell death during infection, we discovered that Shigella infection induced acute inflammatory, caspase-4-dependent epithelial cell death, which is counteracted by the bacterial OspC3 effector. OspC3 interacts with the caspase-4-p19 subunit and inhibits its activation by preventing caspase-4-p19 and caspase-4-p10 heterodimerization by depositing the conserved OspC3 X1-Y-X2-D-X3 motif at the putative catalytic pocket of caspase-4. Infection of guinea pigs with a Shigella ospC3-deficient mutant resulted in enhanced inflammatory cell death and associated symptoms, correlating with decreased bacterial burdens. Salmonella Typhimurium and enteropathogenic Escherichia coli infection also induced caspase-4-dependent epithelial death. These findings highlight the importance of caspase-4-dependent innate immune responses and demonstrate that Shigella delivers a caspase-4-specific inhibitor to delay epithelial cell death and promote infection

A novel missense mutation of SLC7A9 frequent in Japanese cystinuria cases affecting the C-terminus of the transporter

Cystinuria is caused by the inherited defect of apical membrane transport systems for cystine and dibasic amino acids in renal proximal tubules. Mutations in either SLC7A9 or SLC3A1 gene result in cystinuria. The mutations of SLC7A9 gene have been identified mainly from Italian, Libyan Jewish, North American, and Spanish patients. In the present study, we have analyzed cystinuria cases from oriental population (mostly Japanese). Mutation analyses of SLC7A9 and SLC3A1 genes were performed on 41 cystinuria patients. The uptake of 14C-labeled cystine in COS-7 cells was measured to determine the functional properties of mutants. The protein expression and localization were examined by Western blot and confocal laser-scanning microscopy. Among 41 patients analyzed, 35 were found to possess mutations in SLC7A9. The most frequent one was a novel missense mutation P482L that affects a residue near the C-terminus end of the protein and causes severe loss of function. In MDCK II and HEK293 cells, we found that P482L protein was expressed and sorted to the plasma membrane as well as wild type. The alteration of Pro482 with amino acids with bulky side chains reduced the transport function of b0,+AT/BAT1. Interestingly, the mutations of SLC7A9 for Japanese cystinuria patients are different from those reported for European and American population. The results of the present study contribute toward understanding the distribution and frequency of cystinuria-related mutations of SLC7A9

製図教育用ネットワークコンピュータテストシステムの開発とその評価

著者らはこれまでに製図教育用コンピュータテストシステムを開発し、数年間にわたり、実際に利用してその効果を検討してきた。このテストシステムは、製図の2つの能力、すなわち立体をイメージする能力と三面図への変換能力を分離測定することができるものである。そこで、テストシステムを使ってこの能力が身についているかどうかを判定するが、イメージ能力が十分に身に付いていない学習者は、何度もシステムを使ってテストを受験することで、得点の向上がはかれた。すなわち、テストシステムは自主学習システムとして役立った。さらにスタンドアロン型のテストシステムを発展させ、ネットワーク上にこのコンピュータテストシステムを構築したところ、学習者は空間的・時間的に自由にシステムを利用できるようになり、スタンドアロン型のテストシステムよりさらに自主学習者が増加した。また、自主学習システムとして利用した場合には、学習者のシステムに対する主観的評価が高まることもわかった。A computerized testing system previously developed by the authors for mechanical drawing education can assess two different skills independently. Learners whose skills had lagged behind achieved better marks through repeated experience in the examination using this test system. In other words, the test system proved to be useful as a self-lerning system. Furthemore, when used as a self-lerning system, lerners\u27 subjective evaluation of the test system improved. Additionally, con- struction of the computerized testing system on the network enabled lerners to use the system without the constraints of time and space. Compared to the results obtained with stand-alone systems, this led to increasing numbers of self-leaners, better marks, and higher evaluation

Integration-Free iPS Cells Engineered Using Human Artificial Chromosome Vectors

Human artificial chromosomes (HACs) have unique characteristics as gene-delivery vectors, including episomal transmission and transfer of multiple, large transgenes. Here, we demonstrate the advantages of HAC vectors for reprogramming mouse embryonic fibroblasts (MEFs) into induced pluripotent stem (iPS) cells. Two HAC vectors (iHAC1 and iHAC2) were constructed. Both carried four reprogramming factors, and iHAC2 also encoded a p53-knockdown cassette. iHAC1 partially reprogrammed MEFs, and iHAC2 efficiently reprogrammed MEFs. Global gene expression patterns showed that the iHACs, unlike other vectors, generated relatively uniform iPS cells. Under non-selecting conditions, we established iHAC-free iPS cells by isolating cells that spontaneously lost iHAC2. Analyses of pluripotent markers, teratomas and chimeras confirmed that these iHAC-free iPS cells were pluripotent. Moreover, iHAC-free iPS cells with a re-introduced HAC encoding Herpes Simplex virus thymidine kinase were eliminated by ganciclovir treatment, indicating that the HAC safeguard system functioned in iPS cells. Thus, the HAC vector could generate uniform, integration-free iPS cells with a built-in safeguard system

Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells

The incidence of distant metastases is higher in the tumours with low oxygen pressure than in those with high oxygen pressure. It is well known that hypoxia induces the transcription of various genes involved in angiogenesis and anaerobic metabolism necessary for the growth of tumour cells in vivo, suggesting that hypoxia may also induce the transcription of metastasis-associated genes. We sought to identify the metastasis-associated genes differentially expressed in tumour cells under hypoxic conditions with the use of a DNA microarray system. We found that hypoxia enhanced the expression of autocrine motility factor mRNA in various cancer cells and also enhanced the random motility of pancreatic cancer cells. Autocrine motility factor inhibitors abrogated the increase of motility under hypoxic conditions. In order to explore the roles of hypoxia-inducible factor-1α, we established hypoxia-inducible factor-1α-transfectants and dominant negative hypoxia-inducible factor-1α-transfectants. Transfection with hypoxia-inducible factor-1α and dominant-negative hypoxia-inducible factor-1α enhanced and suppressed the expression of autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA and the random motility, respectively. These results suggest that hypoxia may promote the metastatic potential of cancer cells through the enhanced autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA expression and that the disruption of the hypoxia-inducible factor-1 pathway may be an effective treatment for metastasis