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In high strain-rate zones, active regions of ongoing crustal deformation, earthquakes occur frequently, the total slip rates of active faults are in the zone not consistent to strain rate detected by geodesy. This difference is one of the most significant issues for crustal deformation, and is known as "strain-rate paradox". Previous crustal deformation models are mainly constructed with major active faults alone, whereas minor faults are often recognized in the high strain-rate zones. The aims of this thesis are to solve the strain-rate paradox and propose a new image of the crustal deformation by focusing on the minor faults. In order to accomplish these goals, the representative high strain-rate zones such as San-in Shear Zone (SSZ) and Niigata-Kobe Tectonic Zone (NKTZ) were targeted. As a result of the topographical and geological approaches, universal model, origin, deformation process and mechanism of the high strain-rate zone were clarified. The main outcomes are as follows: (1) Minor faults in the NKTZ, which are mostly NE-SW to ENE-WSW-trending, have a few mm to a few dozens of cm in width and exhibit dextral sense of shear. These minor faults are distributed in the vicinity and/or away from the major active faults. In addition, the active fault, whose core zone has 5 m in thickness, were found. Such fault showed dextral sense of shear and has the latest slip event after AD 1521-1658, suggesting that the fault clearly contribute to the dextral deformation of the NKTZ. The origins of such faults are thought to be tensile cracks formed in Cretaceous, suggesting that the faults contribute to the dextral deformation of the NKTZ after repeated faulting along the cracks. The minor faults away from the major active faults are also thought to contribute to the deformation of the NKTZ, whereas minor faults outside of the NKTZ cannot contribute to that of the NKTZ. (2) Minor faults in the SSZ, which are mostly ENE-WSW to NE-SW-trending, have a few mm to a few dozens of cm in width and exhibit dextral sense of shear. These other minor faults trending NW-SE ～ NNW-SSE direction with steep dips, are sinistral sense of shear. The minor faults, which is trending E-W direction with steep dips, showed dextral sense of shear. Active faults, whose attitude are nearly parallel to the SSZ, are also newly recognized. The thickness of the fault is a few cm and thought to show dextral-reverse oblique slip after 18648-16313 cal. BC. The frameworks of the major active faults in the SSZ are thought to prepared along the geological boundaries and such faults have grown by the repeated activities since Paleogene. It is considered that not only major active faults but also minor faults away from the major active faults can contribute to the dextral motion of the SSZ. On the contrary, there are only reverse fault was recognized in the area outside of the SSZ. (3) The minor fault in the high strain-rate zones, which includes the minor fault away from the major active fault, can contribute to the dextral deformation of the high strain-rate zones because of their attitudes and sense of shears. On the other hand, the minor faults outside of the high strain-rate zones cannot contribute to the dextral deformation of the zone due to their attitudes and sense of shears. Thus, there are noteworthy difference between minor faults in and outside of the high strain-rate zones. Combining these outcomes, a hierarchical structure of the high strain-rate zones can be constructed as follows: (I) fault core of major active faults, (II) damage zone of major active faults, (III) brittle shear zone (or active background; the area beyond the damage zone but in the SSZ), (IV) inactive background (outside of the high strain-rate zone). This new model enables to partly solve the strain rate paradox for both zones, whereas an occurrence of faults differs between the zones. The NKTZ is characterized by NE-SW to ENE-WSW-trending minor faults and their thickness ranging from a few mm to a few dozens of cm. The active faults possess fault core with > 5 m in thickness. The SSZ are characterized by NW-SE or E-W-trending minor faults and their thickness ranging from a few mm to a few dozens of cm. Some faults show the Quaternary activities, whereas fault core with a few meters in thickness were not found. These differences on fault occurrence are considered to be derived from the evolutional processes. It is thought that the repeated activities along the pre-existed structures lead to present active faults. Thus, it can be considered that the faults are assigned in response to the local geological background, which result in dextral contribution to the high strain-rate zones. This study clarified universal model, origin, deformation process and mechanism of the high strain-rate zone by focusing on the minor faults. These achievements can constrain the modeling of the crustal deformation and interpretations of the geodetical observations and can contribute to assessments of large-scale constructions and seismic hazards.

Androgen receptor (AR)-signaling plays an important role in promoting tumor cell survival and the development of castration-resistant prostate cancer (CRPC). Androgen deprivation therapy is the basic therapeutic strategy for AR signaling blockade, but that effects wonʼt last long and most of metastatic prostate cancer show castration resistance. Recently, new agents, AR Axis Targeted agents (ARAT), have been developed. We have been developing our bench-to-bedside translational research to elucidate the mechanisms of drug resistance in prostate cancer. This review describes our investigational results and recent advances in CRPC with ARAT treatment strategy.

The hippocampal dentate gyrus has been identified to play a critical role in maintaining contextual memory in many mammalian species. To evaluate learninginduced synaptic plasticity of granule cells, we subjected male rats to an inhibitory avoidance (IA) task and prepared acute hippocampal slices. In the presence of 0.5 μM tetrodotoxin, we recorded miniature excitatory post synaptic currents (mEPSCs) and inhibitory post synaptic currents (mIPSCs) in male rats experiencing four groups: untrained, IA-trained, unpaired, and walk-through. Compared with the untrained, IA-trained, unpaired, and walk-through groups, the unpaired group significantly enhanced mean mEPSC amplitudes, suggesting the experience-induced plasticity at AMPA receptor-mediated excitatory synapses. For inhibitory synapses, both unpaired and walk-through groups significantly decreased mean mIPSC amplitudes, showing the experience-induced reduction of postsynaptic GABAA receptor-mediated currents. Unlike the plasticity at CA1 synapses, it was difficult to explain the learning- specific plasticity at the synapses. However, overall multivariate analysis using four variables of mE(I)PSC responses revealed experience-specific changes in the diversity, suggesting that the diversity of excitatory/inhibitory synapses onto granule cells differs among the past experience of animals include the learning. In comparison with CA1 pyramidal neurons, granule cells consistently showed greater amplitude and frequency of mE(I)PSCs. Fluctuation analysis further revealed that granule cells provide more postsynaptic AMPA receptor channels and greater single-channel current of GABAA receptors of than CA1 pyramidal neurons. These findings show functional differences between two types of principal cells in the hippocampus.

Incontinentia pigmenti (IP; OMIM# 308300) is a rare inherited disease caused by a mutation of IKBKG, which is also known as NEMO, located on Xq28. IP patients usually present with abnormalities of skin, eyes, nails and central nervous system. The neurological damege, which occur usually from neonatal through the early infantile period, leads to neulogical complication such as development retardation, motor paralysis and epilepsy. However, there has been little study done concerning the effect of therapy for the neural abnormalities. We have investigated the clinical findings in a female IP case with a novel mutation of IKBKG for six years due to disclosing the neurological prognosis and the immunological features. It is hoped that the present study will contribute to a better management of IP patients.

近年、遺伝子改変T細胞を用いた養子免疫療法の臨床応用が進められているが、未だ治療成績は満足のいくものではなく、更なる治療の進歩が求められている。我々はこれまで、自律性にIL7とCCL19を発現するCAR-T細胞（7×19 CAT-R細胞）が優れた抗腫瘍活性を発揮することを示した。本研究ではIL7及びCCL19がTCR-T細胞の抗腫瘍活性を増強させる可能性を検証するため、腫瘍抗原であるP1Aを特異的に認識するTCR-T細胞（P1A-T細胞）にIL7及びCCL19を分泌させる遺伝子改変を加えた7×19 P1A-T細胞を作製した。P1Aを有する細胞株であるP815を皮下接種したマウスに対する養子免疫療法において、7×19 P1A細胞はIL7及びCCL19を分泌しないP1A-T細胞（Conv. P1A-T細胞）と比較し優れた抗腫瘍効果を示した。腫瘍拒絶マウスにおいては、Conv. P1A-T細胞を使用したマウスと比較し優れた免疫記憶が形成されていた。また抗PD-1抗体を用いた複合免疫療法を行うことで、7×19 P1A-T細胞の有する抗腫瘍効果は更に増強された。CRISPR/ Cas9システムを用いPdcd1をknockdownした7×19 P1A-T細胞は対照7×19 P1A-T細胞と比較し強い抗腫瘍効果を示したが、抗PD-1抗体を併用することで更なる抗腫瘍効果の増強を認めたことから、7×19 P1A-T細胞の発揮する抗腫瘍効果には7×19 P1A-T細胞そのものばかりでなくマウス内在性のT細胞が関与していることが分かった。また、7×19 P1A-T細胞においても抗PD-1抗体との併用により抗腫瘍効果が増強することを確認した。本研究における検証により、7×19 TCR-T細胞及び7×19 CAR-T細胞を用いた免疫療法が抗悪性腫瘍療法の発展に寄与できる可能性が示された。

背景：経食道心エコー図検査（TEE）は、心房細動（AF）に対する肺静脈隔離術（PVI）前の左心房（LA）および左心耳（LAA）における血栓の有無の評価を行うゴールドスタンダードな検査である。TEEは比較的安全とされているが、近年PVIに先行するTEEが食道粘膜損傷（EMI）を引き起こす可能性があることが報告された。 目的：PVIを施行したAF患者におけるTEE関連EMIの発生率とその危険因子を検討すること。 方法と結果：3D TEEプローブを用いた術前TEEと術後上部消化管内視鏡検査を受けたPVI患者262人を対象とした。TEE関連EMIは16人（6.1%）の患者（18病変）、PVI関連EMIは5人（1.9%）の患者（8病変）で認められた。TEE関連EMIは上部食道の右側と中部食道の左前側で多く認められた。1人の患者で軽度の胸部違和感を認めた。多変量解析では、高齢はTEE関連EMIの独立した危険因子であった（オッズ比1.08、95%信頼区間1.01-1.16；P=0.0274）。 結語：3D TEEプローブによるTEE関連EMIは、PVI施行患者の6.1%で認められ、高齢であることはTEE関連EMIの危険因子であった。これらの所見から、特に高齢患者においては、LA・LAAにおける血栓評価として他の画像診断を考慮する必要があるかもしれない。

本研究は挫折体験により知覚されたストレスとフォーカシング的態度および自己成長感との関連を検討するものである。パス解析の結果，(1)挫折体験により知覚されたストレスは問題意識性を高め，フォーカシング的態度による吟味のプロセスを経て自己成長感を高めること，(2)挫折体験により知覚されたストレスはフォーカシング的態度を抑制することが示された。あわせて本研究の結果が臨床に示唆する意義について議論した。

本研究の目的は，教員の教育相談研修への参加意欲を高める要因について検討することである。筆者が行った教育相談の継続研修の参加者14名を対象に，研修に継続参加した理由について自由記述による質問紙調査を行った。検討の結果，研修参加の要因として「ニーズや実践とつながる研究内容」「自分を見つめる・他者と共有し受け止められる時間」は「ニーズや実践とつながる研究内容」や「研究方法・環境の工夫」の両方の側面を持つと考えた。

本研究は質問紙調査により挫折体験の意味づけとフォーカシング的経験および外傷後成長（Post-Traumatic Growth，以下“PTG”と表記）との関連を検討するものである。パス解析の結果，（1）フォーカシング的経験のうち「体験過程の受容と行動」はPTGを促進すること，（2）挫折体験の意味づけのうち「同化」はフォーカシング的経験の「間が取れている」と「体験過程の確認時間・空間の確保」，「体験過程の受容と行動」を促進し「体験の感受」を抑制すること，また（3）挫折体験の意味づけのうち「調節」は「体験の感受」と「体験過程の受容と行動」を促進すること，（4）人は挫折体験を経験した際，「同化」と「調節」の両方を体験しがちであることが示された。以上より「同化と調節の振り子モデル」が提示され，調節のみならず同化も有機体の実現傾向のあらわれとして位置づけうること，また一見進んでいないようにみえるクライエントのプロセスを受容することが，結果としてプロセスを進めることにつながるうることが示唆された。

本研究の目的は，文献をもとに「育児困難感」と「育児不安」の用語の整理を行い，今後の支援に繋げる視点を得ることである。検討の結果，「育児困難感」は，実際の母親を取り巻く要因の中で，母親が子どもと対峙することで「母親自身が困っている」状態を示すものと考えられた。また「育児不安」は「育児における漠然とした不安」であり，疲労感や抑うつ状態が生じる可能性や，具体的な対象や問題がない場合でも生じることが考えられた。また「育児困難感」は「相手（子ども）への感情」であり，「育児不安」は「母親自身の不安」であり，2つは質的に異なると考えられ，「育児困難感」と「育児不安」の高低をもとに，5つのタイプに分類を試みた。

Zero-determinant strategies are a class of memory-one strategies in repeated games which unilaterally enforce linear relationships between payoffs. It has long been unclear for what stage games zero-determinant strategies exist. We provide a necessary and sufficient condition for the existence of zero-determinant strategies. This condition can be interpreted as the existence of two different actions which unilaterally adjust the total value of a linear combination of payoffs. A relation between the class of stage games where zero-determinant strategies exist and other class of stage games is also provided.

Background and Aim: Image definition and complete small bowel examination rate are possible factors contributing to missed lesions during capsule endoscopy.This study aimed to determine the effect of coadministration of polyethylene glycol (PEG) and dai-kenchu-to (DKT) on these factors using PEG and DKT as pretreatment before capsule endoscopy. Methods: Patients who underwent capsule endoscopy at our hospital between November 2007 and August 2012 were included in the study. Patients were divided into the following three groups: those receiving no pretreatment (control, n=133), those orally administered PEG (PEG, n=20), and those orally administered PEG and DKT (15g) (PEG + DKT, n=25). Image definition and complete small bowel examination rate were examined retrospectively between the three groups. Results: Image definition in the PEG + DKT group was significantly higher than that in the control group (p<0.05), but there was no significant differences between the PEG and control groups. The complete small bowel examination rate was significantly lower in the PEG group than in the control and PEG + DKT groups (p<0.05). Conclusions: Coadministration of PEG and DKT improved image definition and prevented a reduction of the complete small bowel examination rate due to PEG in capsule endoscopy.

Application of cell therapy using stem cell into intractable diseases has been noted as the medicine in the next generation taking the place of organ transplantation. Bone marrow cells have been focused as a candidate of the source of this therapy. Liver failure is a terminal state of all advanced liver diseases and thousands of patients are dying of decompensated liver cirrhosis in every year in Japan. Liver transplantation must be the strongest weapon to relieve those patients. However, particularly in Japan, liver transplantation has not been popularized. In this sense, we thought of autologous bone marrow cells transplantation for decompensated liver cirrhosis. Basic studies using animal model revealed that transplanted bone marrow cells into syngenic mouse suffering from liver cirrhosis migrated into the damaged liver and transdifferentiated to the hepatocytes. Based upon the animal studies, clinical trial of this new cell therapy supported by the Ministry of Health, Labor and Welfare is ongoing. It is early to estimate this therapy. However, free from liver failure has been observed in some cases.

Hepatocellular carcinoma (HCC) has a poor prognosis even after curative surgery, due to the high frequency of early intrahepatic recurrence (IHR). Conventional staging systems are almost completely inadequate, and need to be complemented by novel tools. To this end, many investigators have performed DNA microarray analysis on the basis of genome-wide information. However, so far, few studies have been able to truly account for the clinical efficacy of DNA microarray analysis in HCC. To address this dilemma, we used a supervised learning method with information of 7070 genes from 33 HCC samples, to construct a 12-gene predictor for early IHR, and then evaluated its predictive performance in 27 independent HCC samples. Our 12-gene predictor correctly predicted early IHR or non-recurrence in 25 (93%) of the 27 independent samples. This predictive value is higher than that of any other system currently available, suggesting that our system can serve as a robust tool for accurate prediction of early IHR of HCC. I emphasize in this mini-review that, although there are some technical issues to resolve prior to clinical use, DNA microarray technology can provide molecular basis to initiate “bench to bedside” translation, which cannot be easily reached with other methods.

Histopathological and immunohistochemical studies were conducted to investigate the local existence and distribution of mast cells, fibroblasts or dendritic cells, and myofibroblasts in scleroderma, while paying particular attention to the interstices around the adnexa. The skin tissues in 15 cases of systemic scleroderma were classified histopathologically into three stages: early, fully developed, and late stage. Mesenchymal cells were distinguished immunohistochemically by 6 markers: tryptase, CD34, factor XIIIa, alpha smooth muscle actin (αSMA), vimentin, and desmin. In scleroderma, there was an increase in the number of tryptase-positive mast cells in the interstices around the adnexa. With no relation to the interstitial sites, there was a significant decrease in the number of CD34-positive cells in the late stage, and a significant increase in αSMA-positive cells in the fully developed stage, but a decrease in the late stage. Results of the present study brought about the following new findings: it was only in the mast cells that there was a significant difference in the cell distribution between the interstices around the adnexa and the interstices in non-adnexal sites. Secondly, it was suggested that mast cells, CD34-positive dendritic cells, and αSMA-positive myofibroblasts were involved in the fibrosis and shrinkage or disappearance of the adnexa when scleroderma developed.

The purpose of this study was to compare demographic trends in the aging of the Japanese and Brazilian populations on the basis of health indicator data collected by the statistics bureaus of the Japanese and Brazilian governments. The demographic and health indicator data from surveys by the Statistics Bureaus of the Japanese and Brazilian governments and other sources were obtained from websites. The data showed that Japan has an aging population, that the number of elderly persons in Japan is increasing and that the Government of Japan has a plan to address future demands for health resources by this aging population, whereas Brazil has a rapidly population aging but no plan for its future health services. Brazil may need to increase the number of hospitals and hospital beds and develop a medical care plan for the elderly within its Unified Health System.