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形態: カラー図版あり, Physical characteristics: Original contains color illustrations, Accepted: 2021-09-29, 資料番号: PA2210021000

形態: カラー図版あり, Physical characteristics: Original contains color illustrations, Accepted: 2021-05-11, 資料番号: PA2210007000

形態: カラー図版あり, Physical characteristics: Original contains color illustrations, Accepted: 2020-06-15, 資料番号: PA2010059000

近年、世界的に経済特区(SEZ)が急増している。その理由と新動向について、国連の世界投資白書2019年版に依拠しつつ地域別に考察した。また、UNIDOの報告書により、経済特区を含む５つの経済区域(EZ)の段階的発展論と工業団地等の諸概念について検討した。これにより、内生的経済循環と経済特区との関連については、多国籍企業の輸出加工区の規制緩和や定義の多様化、外資誘致に伴う「底辺への競争」などの問題点と課題を考察した。, 同志社大学商学部創立七十周年記念論文集(Special issue in commemoration of the 70th anniversary of the Faculty of Commerce)

The alternative oxidase (AOX) is a monotopic diiron carboxylate protein which catalyzes the four-electron reduction of dioxygen to water by ubiquinol. Although we have recently determined the crystal structure of Trypanosoma brucei AOX (TAO) in the presence and absence of ascofuranone (AF) derivatives (which are potent mixed type inhibitors) the mechanism by which ubiquinol and dioxygen binds to TAO remain inconclusive. In this article, ferulenol was identified as the first competitive inhibitor of AOX which has been used to probe the binding of ubiquinol. Surface plasmon resonance reveals that AF is a quasi-irreversible inhibitor of TAO whilst ferulenol binding is completely reversible. The structure of the TAO-ferulenol complex, determined at 2.7 A, provided insights into ubiquinol binding and has also identified a potential dioxygen molecule bound in a side-on conformation to the diiron center for the first time.

Pharmacological inhibition of histone deacetylase 6 (HDAC6) is an effective therapeutic strategy for cancer and immunological diseases. Most of the previously reported HDAC6 inhibitors have a hydroxamate group as a zinc binding group (ZBG), which coordinates to the catalytic zinc ion of HDAC6. The hydroxamate group is liable to metabolically generate mutagenetic hydroxylamine; therefore, non-hydroxamate HDAC6 inhibitors would be advantageous. In this study, to identify novel non-hydroxamate HDAC6-selective inhibitors, screening of a chemical library and the subsequent structural optimization were performed, which led to the identification of HDAC6-selective inhibitors with 3,3,3-trifluorolactic amide (TFLAM) as a novel ZBG. The identified inhibitor showed potent and selective HDAC6-inhibitory activity in cells and induced regulatory T (Treg) cell differentiation.

With the advancement of space missions and increasing complexity of spacecraft systems, traditional development methods that rely on experience and past examples are approaching the limits. A flexible and robust design space search method based on a systematic approach is required to accomplish challenging space missions. This paper presents a global trajectory optimization framework via a multi-fidelity approach that utilizes a graphics processing unit (GPU) for low-fidelity initial solution search and a central processing unit (CPU) to determine high-fidelity feasible solutions compliant with imposed constraints. A mission scenario employing transfer from a near-rectilinear halo orbit (NRHO) to a low lunar orbit (LLO) is considered to demonstrate the proposed framework, which consists of the following specific processes: (1) identifying a multitude of feasible trajectories as potential global optimum solutions with the aid of super-parallelized trajectory propagation using single-precision GPU cores; and then (2) determining accurate trajectories by means of gradient-based optimization incorporating double-precision propagation using CPU cores. The resultant trajectories are assessed via machine learning to identify the clustering structure, and verified in the light of the primer vector theory that evaluates local optimality in terms of minimum fuel consumption.

2018 IEEE Aerospace Conference (March 3-10, 2018. Yellowstone Conference Center), Montana, USA, 形態: カラー図版あり, Physical characteristics: Original contains color illustrations, 資料番号: PA1810037000

Rosai-Dorfman disease is also known as sinus histiocytosis with massive lymphadenopathy. Extranodal Rosai-Dorfman disease has been reported in ~ 43% of cases; the most frequent extranodal sites – skin, soft tissue, bone, respiratory tract, and eye – are usually involved in association with lymphadenopathy. Lack of lymph node involvement is rare, especially when patients manifest renal disease. Here, we describe a patient who developed membranoproliferative glomerulonephritis when lymphadenopathy was absent. During follow-up for sinus histiocytosis, a 7-year-old Japanese boy developed proteinuria and hematuria. No renal abnormality was present in ultrasound imaging. Histologic examination of a renal biopsy specimen disclosed moderate mesangial proliferation, focal thickening of glomerular capillary walls, and mesangial interposition. Mononuclear cells infiltrated the interstitium. Immunofluorescence showed intense IgG, C3, and C4 reactivity in portions of the mesangium and glomerular capillary walls. Electron microscopy depicted nodular deposits in mesangial, endocapillary, and subepithelial areas. Immunohistochemistry for S-100 protein, CD68, and lysozyme was positive within the interstitium. CD1a staining was absent. These findings were diagnostic for membranoproliferative glomerulonephritis. Multidrug therapy, including methylprednisolone and mizoribine, improved urinary findings and induced complete remission of both diseases. To the best of our knowledge, this is the first report of Rosai-Dorfman disease complicated by renal disease in the absence of concurrent nodal involvement. Clinicians should be alert to this diagnostic possibility.

Electroconvulsive therapy (ECT) is an effective treatment for major depression. Previous studies suggested that dopaminergic neurotransmission plays a crucial role in the mechanism of the action of ECT. Since dopamine transporters (DAT) regulate extracellular dopamine concentration, DAT represents an interesting target for the study of the mechanism of action of ECT. Eight inpatients (7 patients with major depressive disorder and 1 patient with bipolar disorder with a DSM-IV diagnosis) received a series of 7-15(11.3±5.2) bilateral ECT sessions.The severity of symptoms was assessed using the 21-item Hamilton Depression Rating Scale (HDRS) and Clinical Global Impression-Severity (CGI-S). All patients were examined with [

This paper presents a precise rendezvous guidance technique in low Earth orbit (LEO) via machine learning. The guidance law must be tolerant of such disturbances as variations of initial conditions due to navigation and/or control errors. Precise relative trajectory control is a particularly key technology in the proximity operation in terms of safety requirements such as collision avoidance. The conventional guidance law in LEO utilizes the Clohessy-Wiltshire solution that is the analytical solution of Hill's equation restricted in circular orbits. This solution is characterized by being able to control the position of a spacecraft at a specific timing, whereas the spacecraft's velocity at the same timing is dependent on estimated orbital states at the timing of impulsive maneuver. Excessive guidance error in terms of velocity results in a wider dispersion of relative trajectories, possibly resulting in trajectories with less safety. It may lead to strict accuracy requirements on navigation sensors or control devices, thereby requiring the recognition of guidance accuracy as a potential cost driving factor in a space mission project. The proposed method aims at improving guidance velocity errors by controlling maneuver impulse timing. It utilizes a linear regression modeling approach to predict optimum impulse timing. The linear regression model that estimates guidance velocity error is formulated by utilizing all elements of disturbances and maneuver impulse timing. An optimum maneuver impulse timing is predicted by utilizing all elements of disturbances as derived from the onboard navigation solution, given the predefined target value of the guidance velocity error. Conventional rendezvous guidance trajectory planning assumes a fixed maneuver impulse timing to simplify the planning, which results in less precise guidance accuracy. The proposed methodology is an innovative way to overcome this concern by implementing a simple algorithm with a light computation load.

Electroconvulsive therapy (ECT) is an effective treatment for major depression. Previous studies suggested that dopaminergic neurotransmission plays a crucial role in the mechanism of the action of ECT. Since dopamine transporters (DAT) regulate extracellular dopamine concentration, DAT represents an interesting target for the study of the mechanism of action of ECT. Eight inpatients (7 patients with major depressive disorder and 1 patient with bipolar disorder with a DSM-IV diagnosis) received a series of 7–15(11.3±5.2) bilateral ECT sessions.The severity of symptoms was assessed using the 21-item Hamilton Depression Rating Scale (HDRS) and Clinical Global Impression-Severity (CGI-S). All patients were examined with [18F]FE-PE2I positron emission tomography (PET) at pre-ECT, after the 10th ECT, and at post-ECT. Striatal DAT-binding potential (BPND) of all patients was reduced, with an average change ratio of DAT-BPND of -13.1±5.6%. In the 2 cases with 15 ECT sessions, the ratio change of DAT-BPND after the 15th ECT was larger than that after the 10th ECT. Also, HDRS and CGI-S were reduced. These results indicate that the dopamine nervous system is part of themechanism of action of ECT.

X-linked lymphoproliferative syndrome type 1 (XLP1) is a rare congenital immunodeficiency disease. We report the case of an 18-year-old male who developed hemophagocytic lymphohistiocytosis (HLH) with neurologic complications after primary Epstein-Barr virus (EBV) infection and subsequently developed EBV-related central nervous system lymphoma (CNSL). Given the vulnerability to EBV, he was finally diagnosed with XLP1 and treated with whole-brain irradiation along with chemotherapy and subsequent allogeneic hematopoietic stem cell transplantation from a SH2D1A wild-type sibling donor. Although the prognosis for CNSL is generally dismal, reconstitution of the immune system from a normal donor contributed to the patient remaining in remission for 30 months.

Both biological and psychological interventions are important in the treatment of Alzheimer's disease(AD). Although there is no curative therapy for AD, current interventions that focus mainly on their cognitive functions are neither sufficient nor effective. More atten- tion should be paid to their self-efficacy in daily life. When people develop AD, they will lose their self-respect and social role or relationships. The aim of the treatment for AD is simply to regain these, which will not be successful unless their daily lives become the target of sharp focus. Behavioral and psychological symptoms of dementia (BPSD) are also strongly associated with patients'daily life rather than with their cognitive function. Upon medical examinations, psychiatrists should not only listen to patients' caregivers, but also provide psychotherapy for the AD patients themselves, despite their being cognitively more or less impaired. Psychiatrists have to inform caregivers about the loneliness AD patients feel and the importance of respecting their feelings. Regarding pharmacotherapy, discussion concerning the best for each patient's condition among the four kinds of current anti-dementia drugs would not be useful, as each patient's condition, inclusive of BPSD, does not only depend on their neurological impairment. General function of the brain is largely normal in AD patients at early stage, therefore rarely causing BPSD. What may well cause BPSD are the patients' circumstances including social interaction between caregivers and themselves in their daily life. Thus, psychi- atrists need to keep in mind both biological and psychological factors in the treatment of AD.

We describe our experience with a 12 year-old girl with kaposiform hemangioendothelioma accompanied by Kasabach–Merritt phenomenon with exacerbation of the disease 10 years after the initial diagnosis. Kaposiform hemangioendothelioma infiltrated into the subcutaneous tissue of the facial skin with deterioration of coagulopathy despite conventional therapies including corticosteroid, vincristine, and propranolol. Sirolimus, a mammalian target of rapamycin inhibitor, produced rapid and dramatic improvement of the Kasabach–Merritt phenomenon and kaposiform hemangioendothelioma shrinkage. Eventually, multifocal lesions of kaposiform hemangioendothelioma disappeared on the images of magnetic resonance imaging and have remained in remission for 27 months after sirolimus cessation. We demonstrated that the AKT/mammalian target of rapamycin signaling pathway played a pivotal role in the kaposiform hemangioendothelioma growth. Sirolimus must be a strong candidate for molecular therapy targeting kaposiform hemangioendothelioma.

研究(Article)

Epidemiological research has indicated that elderly patients with depression are at increased risk of subsequent dementia including Alzheimer’s disease. In addition, several studies have also shown that depressive pseudodementia may well develop into irreversible dementia. It is a matter of course, however, that all depressive patients with pseudodementia do not progress to irreversible dementia. The present case is an elderly woman with psychotic depression who was misdiagnosed with dementia because of poor response to serotonin selective reuptake inhibitor (SSRI) and serotonin and norepinephrine reuptake inhibitor (SNRI) as well as a manifestation of moderate cognitive impairment. She was remitted with pharmacotherapy by tricyclic antidepressant (TCA), with no cognitive problems. Psychiatrists should take care not to give too much weight to certain evidence that pseudodementia is a strong predictor of dementia, and should observe individual depressive patients carefully and treat them in any possible way including with TCA or electroconvulsive therapy.

Antipsychotics have often been administered to treat delirium and intractable insomnia in elderly patients with or without dementia. However, antipsychotics sometimes cause severe adverse effects. We report two cases of very elderly patients who developed pre-shock after the administration of antipsychotics in a clinical consultation-liaison setting. These cases suggest that antipsychotics can induce fatal adverse events in very elderly patients. Although there has been little evidence regarding the most appropriate kind of drug and dosage for such patients, psychiatrists should exercise great caution in the use of antipsychotics for the very elderly, including deciding to prescribe the lowest dose or not prescribing them at all.

FK506 (tacrolimus), a macrolide compound with immunosuppressant activity, has been proven to have clinical importance and has been manufactured industrially since 1993 by using mutants with high FK506-production ability; these mutants have been developed from the wild strain Streptomyces tsukubaensis No. 9993. FR900525 is one of the by-products of FK506 production. However, there was no effective industrial method to separate FR900525 from FK506 due to the structural similarity between the two compounds. Therefore, reducing the level of FR900525 was a serious problem in the industrial strain A. In this study, we aimed to reduce the FR900525 production. We first determined that pipecolic acid level was a critical parameter for controlling FR900525 production in strain A. S-(2-Aminoethyl) l-cysteine (AEC)-resistant mutants has been reported to increase lysine productivity successfully in a variety of lysine-producing microorganisms. Therefore, next, we applied a selection of AEC-resistant mutants to enhance pipecolic acid biosynthesis. Finally, four AEC-resistant mutants were obtained from strain A using ultraviolet irradiation, and three of them showed less FR900525 productivity compared to the parental strain A. Our findings indicated that AEC resistance was effective phenotype marker for increasing pipecolic acid productivity and for reducing FR900525 production in S. tsukubaensis. Thus, our study provides an efficient method for reducing FR90025 level during FK506 biosynthesis.