He Wahine, He Whenua I Ngaro Ai? Maori Women, Maori Marriage Customs and the Native Land Court, 1865-1909.

The aim of this study is to investigate and identify the effects the Native Land Court and native land legislation had on customary Māori marriage practices from 1865 to 1909. While researchers have produced a variety of important understandings of the court’s role in promoting land loss in Māori society, Māori women’s involvement in the court and its effects upon them is just beginning to be examined. This thesis makes a contribution to Māori women’s history by accounting for the role the Native Land Court and associated land legislation played in reshaping customary Māori marriage practices in nineteenth and early twentieth century New Zealand. Even though native land legislation was one of the key mechanisms by which the state governed Māori land as well as marriage, this connection is rarely examined within the same frame. The Native Land Court is a forum where land and marriage did interact. Focusing on a case study of Ngāti Kahungunu, I situate prominent Māori women in the Native Land Court, and use their experiences to further understandings of how Māori marriage, which is often examined in a pre-European context, was shaped by land title investigations and succession cases. This study was conducted utilising statutes, colonial newspapers and the Napier Minute Books. In the first chapter, this thesis uses ethnographic material to describe and interpret marriage customs prior to European contact, its draws upon missionary understandings of customary marriage upon arrival to Aotearoa, and also traces how colonial law managed marriage prior to the Native Land Court 1865. This provides vital contextual information for the later chapters. The next chapter discusses native land and marriage laws between 1865 and 1890 and how they affected customary Māori marriage practices. Chapter Three examines three prominent Māori women involved in well-known legal cases. The final chapter discusses Māori women’s political organising and traces their attempts to protect and retain land during the 1890s. The thesis ends with a discussion of the Native Land Act 1909, a significant consolidating act. Focusing on the overarching structures of the law and its effects on customary Māori marriage allows this study to consider the broader effects it had on Māori society. What emerges from the study is how whakapapa and kinship structures underpin and inform Māori marriage, and how Māori forms of celebration continued to be practiced into the early twentieth century. Nonetheless, a main driver of change lay in assimilation policies that directed native land legislation towards individualisation of title, which undermined Māori women’s access to own and manage land

カルニチン/有機カチオントランスポーター(OCTN2)のpharmacophoreに関する研究

取得学位：博士(薬学)，学位授与番号：博甲第596号，学位授与年月日：平成15年9月30日,学位授与年：200

PEMBANGUNAN PASAR SALAMAN DI KABUPATEN MAGELANG

Perkembangan sektor ekonomi yang terus meningkat di Indonesia perlu diiringi dengan peningkatan sarana dan prasarana yang berkualitas. Pasar merupakan salah satu aspek penunjang untuk membantu meningkatkan sektor perekonomian suatu wilayah. Oleh karena itu, dibutuhkan peningkatan infrastuktur pasar yang layak dan memadai, mulai dari pasar tradisional hingga pasar modern, termasuk salah satunya Pasar Salaman yang terletak di Kecamatan Menoreh, Kabupaten Magelang, Provinsi Jawa Tengah. Pembangunan Pasar Salaman ini diharapkan dapat membantu meningkatkan kualitas sektor perekonomian masyarakat sekitar. Peningkatan infratuktur pasar perlu diselaraskan dengan kulitas stukrtur bangunan yang kuat dan memiliki tahanan terhadap bencana alam. Mengingat Indonesia termasuk salah satu negara rawan bencana, utamanya gempa bumi. Selain itu, pembangunan Pasar Salaman ini juga disesuaikan dengan aturan-aturan, seperti Standar Nasional Indonesia (SNI), Peraturan Pemerintah, dan referensi lain yang berlaku. Perencanaan pembangunan Pasar Salaman meninjau pada 3 aspek utama, yaitu aspek struktur atas, struktur bawah, serta manajemen proyek. Aspek struktur atas mencakup perencanaan atap, kolom, balok, pelat lantai, dan tangga. Selanjutnya, untuk struktur bawah mencakup analisis daya dukung tanah, jenis fondasi, serta analisis likuifaksi (penururnan) tanah. Terdapat 3 bangunan utama yang direncanaakan pada pembangunan Pasar Salaman, yaitu Bangunan A, Bangunan B, dan Bangunan D. Aspek struktur atas direncanakan rangka kuda-kuda profil atap direncanakan menggunakan 2L 65x65x6 untuk eksterior, 2L 60x60x5 untuk interiornya, dan profil gording C 100x50x20 tebal 2 mm dengan sagrod berdiameter 8 mm. Dimensi kolom yang digunakan berukuran 350 x 350 mm dan 350 x 500 mm, sedangkan dimensi balok menggunakan 250 x 400 mm untuk balok induk dan 200 x 300 mm untuk balok anak. Perencanaan pelat lantai dan pelat tangga menggunakan tebal 130 mm. Sebaliknya, pada struktur bawah pembangunan Pasar Salaman direncanakan menggunakan 2 jenis fondasi, yaitu fondasi dangkal dan fondasi dalam. Rencana fondasi dangkal menggunakan tipe fondasi footplat pada kedalaman 2 m, sedangkan untuk fondasi dalam direncanakan menggunakan tipe fondasi bored pile pada kedalaman fondasi 4 m. Selain itu, manajemen proyek dibutuhkan dalam suatu perancangan guna mendapatkan kesesuaian biaya dan durasi yang telah ditetapkan. Proyek konstruksi seringkali mengalami ketidaksesuaian biaya dan durasi proyek pada saat pelaksanaannya. Oleh karena itu, manajemen proyek memiliki peran penting pada suatu proyek konstruksi, agar waktu atau durasi proyek dapat diselesaikan tepat pada waktunya atau lebih singkat, sehingga pembengkakan biaya juga dapat diminimalisir bahkan tidak ada. Estimasi total biaya yang dibutuhkan dalam proyek pembangunan Pasar Salaman senilai Rp8.388.922.658 dengan durasi pekerjaan 215 hari untuk Bangunan A, 109 hari untuk Bangunan B, dan 180 hari untuk Bangunan

Case report: Ensitrelvir for treatment of persistent COVID-19 in lymphoma patients: a report of two cases

Persistent COVID-19 is a well recognized issue of concern in patients with hematological malignancies. Such patients are not only at risk of mortality due to the infection itself, but are also at risk of suboptimal malignancy-related outcomes because of delays and terminations of chemotherapy. We report two lymphoma patients with heavily pretreated persistent COVID-19 in which ensitrelvir brought about radical changes in the clinical course leading to rapid remissions. Patient 1 was on ibrutinib treatment for mantle cell lymphoma when he developed COVID-19 pneumonia which was severe and ongoing for 2 months despite therapy with molnupiravir, multiple courses of remdesivir, one course of sotrovimab, tocilizumab, and steroids. Patient 2 was administered R-CHOP therapy for diffuse large B-cell lymphoma when he developed COVID-19 which was ongoing for a month despite treatment with multiple courses of remdesivir and one course of sotrovimab. A 5-day administration of ensitrelvir promptly resolved the persistent COVID-19 accommodated by negative conversions of RT-qPCR tests in both patients within days. Ensitrelvir is a novel COVID-19 therapeutic that accelerates viral clearance through inhibition of the main protease of SARS-CoV-2, 3-chymotrypsin-like protease, which is vital for viral replication. Ensitrelvir is a promising treatment approach for immunocompromised lymphoma patients suffering from persisting and severe COVID-19

3 Tesla MRI detects accelerated hippocampal volume reduction in postmenopausal women

Purpose To clarify age-related structural changes specific to hippocampal volume by hierarchizing according to age, gender, and menopausal status. Many studies report the neuroprotective effects of estrogen and age-related brain volume changes; however, there are no studies regarding age-related change specific to hippocampal volume in terms of age, gender, and menopausal status. Materials and Methods T1-weighted MR images were obtained in 412 healthy adults divided into eight groups according to age and gender, to analyze brain volume change focusing on hippocampal volume. Results Voxel-based morphometry (VBM) revealed significantly smaller gray matter volume in the hippocampus bilaterally in females aged in their fifties (51 of 59 females were at menopause) compared with females in their forties (3 of 46 females were at menopause). No significant difference was found, however, between female groups in their fifties versus sixties, or sixties versus seventies; or between male groups in their forties versus fifties, fifties versus sixties, or sixties versus seventies. In addition, VBM revealed significant hippocampal volume reduction bilaterally in all postmenopausal women compared with all premenopausal women. Conclusion The results of the current study suggest that the menopause may be associated with hippocampal volume reduction. © 2010 Wiley-Liss, Inc.Thesis of Goto,Masami / 後藤 政実 博士学位論文(金沢大学 / 大学院医薬保健学総合研究科

Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability

Deubiquitinating enzymes (DUBs) are important regulators of ubiquitin signaling. Here, we report the discovery of deubiquitinating activity in ZUFSP/C6orf113. High-resolution crystal structures of ZUFSP in complex with ubiquitin reveal several distinctive features of ubiquitin recognition and catalysis. Our analyses reveal that ZUFSP is a novel DUB with no homology to any known DUBs, leading us to classify ZUFSP as the seventh DUB family. Intriguingly, the minimal catalytic domain does not cleave polyubiquitin. We identify two ubiquitin binding domains in ZUFSP: a ZHA (ZUFSP helical arm) that binds to the distal ubiquitin and an atypical UBZ domain in ZUFSP that binds to polyubiquitin. Importantly, both domains are essential for ZUFSP to selectively cleave K63-linked polyubiquitin. We show that ZUFSP localizes to DNA lesions, where it plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage. </p

Cysteamine Suppresses Invasion, Metastasis and Prolongs Survival by Inhibiting Matrix Metalloproteinases in a Mouse Model of Human Pancreatic Cancer

Background: Cysteamine, an anti-oxidant aminothiol, is the treatment of choice for nephropathic cystinosis, a rare lysosomal storage disease. Cysteamine is a chemo-sensitization and radioprotection agent and its antitumor effects have been investigated in various tumor cell lines and chemical induced carcinogenesis. Here, we investigated whether cysteamine has anti-tumor and anti-metastatic effects in transplantable human pancreatic cancer, an aggressive metastatic disease. Methodology/Principal Findings: Cysteamine’s anti-invasion effects were studied by matrigel invasion and cell migration assays in 10 pancreatic cancer cell lines. To study mechanism of action, we examined cell viability and matrix metalloproteinases (MMPs) activity in the cysteamine-treated cells. We also examined cysteamine’s anti-metastasis effect in two orthotopic murine models of human pancreatic cancer by measuring peritoneal metastasis and survival of animals. Cysteamine inhibited both migration and invasion of all ten pancreatic cancer cell lines at concentrations (,25 mM) that caused no toxicity to cells. It significantly decreased MMPs activity (IC50 38–460 mM) and zymographic gelatinase activity in a dose dependent manner in vitro and in vivo; while mRNA and protein levels of MMP-9, MMP-12 and MMP-14 were slightly increased using the highest cysteamine concentration. In vivo, cysteamine significantly decreased metastasis in two established pancreatic tumor models, although it did not affect the size of primary tumors. Additionally, cysteamin

Upregulation of mGlu2 receptors via NF-kB p65 acetylation is involved in the proneurogenic and antidepressant effects of acetyl-L-carnitine

Acetyl-L-carnitine (ALC) is a naturally occurring molecule with an important role in cellular bioenergetics and as donor of acetyl groups to proteins, including NF-kappa B p65. In humans, exogenously administered ALC has been shown to be effective in mood disturbances, with a good tolerability profile. No current information is available on the antidepressant effect of ALC in animal models of depression and on the putative mechanism involved in such effect. Here we report that ALC is a proneurogenic molecule, whose effect on neuronal differentiation of adult hippocampal neural progenitors is independent of its neuroprotective activity. The in vitro proneurogenic effects of ALC appear to be mediated by activation of the NF-kappa B pathway, and in particular by p65 acetylation, and subsequent NF-kappa B-mediated upregulation of metabotropic glutamate receptor 2 (mGlu2) expression. When tested in vivo, chronic ALC treatment could revert depressive-like behavior caused by unpredictable chronic mild stress, a rodent model of depression with high face validity and predictivity, and its behavioral effect correlated with upregulated expression of mGlu2 receptor in hippocampi of stressed mice. Moreover, chronic, but not acute or subchronic, drug treatment significantly increased adult born neurons in hippocampi of stressed and unstressed mice. We now propose that this mechanism could be potentially involved in the antidepressant effect of ALC in humans. These results are potentially relevant from a clinical perspective, as for its high tolerability profile ALC may be ideally employed in patient subpopulations who are sensitive to the side effects associated with classical antidepressant