On the mechanism of buckling of a circular cylindrical shell under axial compression

The present paper deals with the buckling of a circular cylindrical shell under axial compression from the viewpoint of energy and the characteristics of deformation. It is shown first, both theoretically and experimentally, that the reason why the buckling of a cylindrical shell is quite different from that of a flat plate is attributable to the existence of a nearly developable surface far apart from the original cylindrical surface. Based upon this result, the experimental fact that the buckling is really not general but local, that is, that the buckled region is limited axially to a range of 1.5 times the wave length of the lobe, is explained by the theoretical result that the minimum buckling load is smaller in the local buckling than in the general buckling case. The occurrence of local buckling is affirmed also from the viewpoint of the energy barrier to be jumped over during buckling, and from a comparison of the theoretical post-buckling state with the experimental results. Finally, the local buckling with the load applied by a spring is analyzed, and it is proved that the minimum buckling load increased with an increase of rigidity of the spring

Functional genomics for breast cancer drug target discovery

Breast cancer is a heterogeneous disease that develops through a multistep process via the accumulation of genetic/epigenetic alterations in various cancer-related genes. Current treatment options for breast cancer patients include surgery, radiotherapy, and chemotherapy including conventional cytotoxic and molecular-targeted anticancer drugs for each intrinsic subtype, such as endocrine therapy and antihuman epidermal growth factor receptor 2 (HER2) therapy. However, these therapies often fail to prevent recurrence and metastasis due to resistance. Overall, understanding the molecular mechanisms of breast carcinogenesis and progression will help to establish therapeutic modalities to improve treatment. The recent development of comprehensive omics technologies has led to the discovery of driver genes, including oncogenes and tumor-suppressor genes, contributing to the development of molecular-targeted anticancer drugs. Here, we review the development of anticancer drugs targeting cancer-specific functional therapeutic targets, namely, MELK (maternal embryonic leucine zipper kinase), TOPK (T-lymphokine-activated killer cell-originated protein kinase), and BIG3 (brefeldin A-inhibited guanine nucleotide-exchange protein 3), as identified through comprehensive breast cancer transcriptomics

Mechanism of Photoregulated Carotenogenesis in Rhodotorula minuta : VI. Changes of Photosensitivity and Induce Capability of Cell to Synthesize Carotenoid

Rhodotorula minutaにおけるカロチノイド生合成の光制御に含まれる光化学反応に関係する物質についての知見を得るために光感応能と誘導能の変化を調べた. 光感応能は光が照射されない限り非常に安定であった. 菌体に光が照射されると光感応能は減少したが,その菌体を生育条件下で培養すると,光感応能は5時聞以内にもとのレベルにまで回復した. 光照射によって獲得したカロチノイド合成の誘導能は,生物化学反応が進行する条件下ではすばやく減少し,5時聞以内に消滅した. しかしながら,生物化学反応が進行しない条件下では極めて安定であった. 光感応能の回復と誘導能の減少は,シクロヘキシミドで阻害された. これらの結果に基づいて,光化学反応に必要な物質－光受容体と反応基質－は菌体中では非常に安定で代謝的分解を受けない事,カロチノイド生合成の誘導因子として作用する光化学反応生成物はタンパク合成の進行と共役してもとの反応基質に戻る事を推察した. 菌体に蓄積されたカロチノイドが光感応能に影響を与えなかったという事実は,光受容体によって吸収される光波長はカロチノイドによって吸収される光波長よりも短いかあるいは長い事を示唆した

Nurse awareness of clinical research : a survey in a Japanese University Hospital

Background: Clinical research plays an important role in establishing new treatments and improving the quality of medical practice. Since the introduction of the concept of clinical research coordinators (CRC) in Japan, investigators and CRC work as a clinical research team that coordinates with other professionals in clinical trials leading to drug approval (registration trials). Although clinical nurses collaborate with clinical research teams, extended clinical research teams that include clinical nurses may contribute to the ethical and scientific pursuit of clinical research. Methods: As knowledge of clinical research is essential for establishing an extended clinical research team, we used questionnaires to survey the knowledge of clinical nurses at Tokushima University Hospital. Five-point and two-point scales were used. Questions as for various experiences were also included and the relationship between awareness and experiences were analyzed. Results: Among the 597 nurses at Tokushima University Hospital, 453 (75.9%) responded to the questionnaires. In Japan, registration trials are regulated by pharmaceutical affairs laws, whereas other types of investigator-initiated research (clinical research) are conducted based on ethical guidelines outlined by the ministries of Japan. Approximately 90% of respondents were aware of registration trials and clinical research, but less than 40% of the nurses were aware of their difference. In clinical research terminology, most respondents were aware of informed consent and related issues, but ≤50% were aware of other things, such as the Declaration of Helsinki, ethical guidelines, Good Clinical Practice, institutional review boards, and ethics committees. We found no specific tendency in the relationship between awareness and past experiences, such as nursing patients who were participating in registration trials and/or clinical research or taking a part in research involving patients as a nursing student or a nurse. Conclusions: These findings suggest that clinical nurses have only limited knowledge on clinical research and the importance to have chances to make nurses aware of clinical research-related issues is suggested to establish an extended research team. Because of the study limitations, further study is warranted to determine the role of clinical nurses in establishing a suitable infrastructure for ethical pursuit of clinical research

Determination of the genetic structure of remnant Morus boninensis Koidz. trees to establish a conservation program on the Bonin Islands, Japan

BACKGROUND: Morus boninensis, is an endemic plant of the Bonin (Ogasawara) Islands of Japan and is categorized as "critically endangered" in the Japanese red data book. However, little information is available about its ecological, evolutionary and genetic status, despite the urgent need for guidelines for the conservation of the species. Therefore, we adopted Moritz's MU concept, based on the species' current genetic structure, to define management units and to select mother tree candidates for seed orchards. RESULTS: Nearly all individuals of the species were genotyped on the basis of seven microsatellite markers. Genetic diversity levels in putative natural populations were higher than in putative man-made populations with the exception of those on Otouto-jima Island. This is because a limited number of maternal trees are likely to have been used for seed collection to establish the man-made populations. A model-based clustering analysis clearly distinguished individuals into nine clusters, with a large difference in genetic composition between the population on Otouto-jima Island, the putative natural populations and the putative man-made populations. The Otouto-jima population appeared to be genetically differentiated from the others; a finding that was also supported by pairwise F(ST )and R(ST )analysis. Although multiple clusters were detected in the putative man-made populations, the pattern of genetic diversity was monotonous in comparison to the natural populations. CONCLUSION: The genotyping by microsatellite markers revealed strong genetic structures. Typically, artificial propagation of this species has ignored the genetic structure, relying only on seeds from Otouto-jima for replanting on other islands, because of a problem with inter-specific hybridization on Chichi-jima and Haha-jima Islands. However, this study demonstrates that we should be taking into consideration the genetic structure of the species when designing a propagation program for the conservation of this species

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3) is predicted to interact with its partner through an ARM-type α-helical structure

Background: Brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3) has been identified recently as a novel regulator of estrogen signalling in breast cancer cells. Despite being a potential target for new breast cancer treatment, its amino acid sequence suggests no association with any well-characterized protein family and provides little clues as to its molecular function. In this paper, we predicted the structure, function and interactions of BIG3 using a range of bioinformatic tools. Results: Homology search results showed that BIG3 had distinct features from its paralogues, BIG1 and BIG2, with a unique region between the two shared domains, Sec7 and DUF1981. Although BIG3 contains Sec7 domain, the lack of the conserved motif and the critical glutamate residue suggested no potential guaninyl-exchange factor (GEF) activity. Fold recognition tools predicted BIG3 to adopt an α-helical repeat structure similar to that of the armadillo (ARM) family. Using state-of-the-art methods, we predicted interaction sites between BIG3 and its partner PHB2. Conclusions: The combined results of the structure and interaction prediction led to a novel hypothesis that one of the predicted helices of BIG3 might play an important role in binding to PHB2 and thereby preventing its translocation to the nucleus. This hypothesis has been subsequently verified experimentally

Diffusion kurtosis imaging with the breath-hold technique for staging hepatic fibrosis: A preliminary study

13301甲第4705号博士（保健学）金沢大学博士論文要旨Abstract 以下に掲載：Magnetic Resonance Imaging 20(47) pp.33-38 2018. Elsevier. 共著者：吉丸 大輔, 宮地 利明, 鈴木 雄一, 濱田 雄貴, 茂木 望, 舟木 歩, 田畑 歩, 増永 敦子, 島田 昌彦, 戸張 真紀, 西野 隆

骨肉腫細胞の生存と増殖はミトコンドリア局在BIG3-PHB2複合体形成に依存する

Previous studies reported the critical role of the brefeldin A–inhibited guanine nucleotide exchange protein 3–prohibitin 2 (BIG3-PHB2) complex in modulating estrogen signaling activation in breast cancer cells, yet its pathophysiological roles in osteosarcoma (OS) cells remain elusive. Here, we report a novel function of BIG3-PHB2 in OS malignancy. BIG3-PHB2 complexes were localized mainly in mitochondria in OS cells, unlike in estrogen-dependent breast cancer cells. Depletion of endogenous BIG3 expression by small interfering RNA (siRNA) treatment led to significant inhibition of OS cell growth. Disruption of BIG3-PHB2 complex formation by treatment with specific peptide inhibitor also resulted in significant dose-dependent suppression of OS cell growth, migration, and invasion resulting from G2/M-phase arrest and in PARP cleavage, ultimately leading to PARP-1/apoptosis-inducing factor (AIF) pathway activation–dependent apoptosis in OS cells. Subsequent proteomic and bioinformatic pathway analyses revealed that disruption of the BIG3-PHB2 complex might lead to downregulation of inner mitochondrial membrane protein complex activity. Our findings indicate that the mitochondrial BIG3-PHB2 complex might regulate PARP-1/AIF pathway-dependent apoptosis during OS cell proliferation and progression and that disruption of this complex may be a promising therapeutic strategy for OS