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Corticobasal degeneration (CBD) is the most common neuropathological substrate for clinically diagnosed corticobasal syndrome (CBS), while identifying CBD pathology in living individuals has been challenging. This study aimed to examine the capability of positron emission tomography (PET) to detect CBD-type tau depositions and neuropathological classification of CBS.

Background:Neuropsychological tests, structural neuroimaging, and functional neuroimaging are employed as diagnostic and monitoring biomarkers of patients with Alzheimer’s disease (AD) Objective:We aimed to elucidate the similarities and differences in neuropsychological tests and neuroimaging with the use of the Mini-Mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-cog), structural magnetic resonance image (MRI), and perfusion single photon emission computed tomography (SPECT), and parametric image analyses to understand its role in AD. Methods:Clinically-diagnosed AD patients (n = 155) were scanned with three-dimensional T1-weighted MRI and N-isopropyl-p-[123I] iodoamphetamine SPECT. Statistical parametric mapping 12 was used for preprocessing images, statistical analyses, and voxel-based morphometry for gray matter volume analyses. Group comparison (AD versus healthy controls), multiple regression analyses with MMSE, ADAS-cog total score, and ADAS-cog subscores as variables, were performed. Results:The AD group showed bilateral hippocampal volume reduction and hypoperfusion in the bilateral temporo-parietal lobe and posterior midline structures. Worse MMSE and ADAS-cog total score were associated with bilateral temporo-parietal volume loss and hypoperfusion. MMSE, but not ADAS-cog, was associated with the posterior midline structures. The ADAS-cog subscores were associated with the temporal volume, while perfusion analyses were linked to the left temporo-parietal region with the language function and right analogous region with the constructional praxis subscore. Conclusion:MMSE and ADAS-cog are associated with temporo-parietal regions, both in volume and perfusion. The MMSE score is associated with posterior midline structures and linked to an abnormal diagnostic AD pattern. Perfusion image analyses better represents the cognitive function in AD patients

Background Individuals with early-onset Alzheimer disease (EOAD) differ from those with late-onset Alzheimer disease (LOAD) not only in genetics and age at onset but also in their clinical symptoms. Objective To differentiate the neuropathological and neurocognitive features of EOAD and LOAD by comparing the pattern of regional gray matter volume (GMV) reduction and its symptomatic correlates. Method Three-dimensional T1-weighted MRIs and Mini-Mental State Examination (MMSE) scores were obtained from 12 individuals with EOAD, 65 with LOAD, and 49 healthy controls (HC). Regional GMV reduction between the three groups was assessed using voxel-based morphometry. Multiple regression analyses were conducted with MMSE total score as an independent variable. Results Compared to the HC, both AD groups showed a significant GMV reduction in the bilateral hippocampus and the left temporoparietal junction; in addition, the LOAD group showed one in the bilateral anterior temporal lobes. Multiple regression analyses revealed a positive correlation between MMSE total score and GMV in the left anterior temporal lobe in both AD groups; that is, lower scores were associated with reduced GMV. Interestingly, a positive correlation in hippocampal GMV was revealed only in the LOAD group. Conclusion MMSE total score is associated with the anterior temporal lobe volume in individuals with AD. Hippocampal volume and its relationship with MMSE total score are associated with LOAD pathophysiology but not EOAD pathophysiology. The hippocampal volume reduction and low MMSE scores are hallmarks of LOAD but are less specific to EOAD, which may cause a delay in diagnosis.

Cerebral blood flow (CBF) and dopamine transporter (DAT) images are clinically used for the differential diagnosis of parkinsonian disorders.This study aimed to examine the correlation of CBF with striatal DAT in patients with Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) and evaluate the diagnostic power of DAT-correlated CBF in PD through machine learning with each imaging modality alone or in combination.Fifty-eight patients with PD and 71 with APS (24 with multiple system atrophy, 21 with progressive supranuclear palsy, and 26 with corticobasal syndrome) underwentThe PD group showed more affected striatal DAT binding positively correlated with the ipsilateral prefrontal perfusion and negatively with the bilateral cerebellar perfusion. In corticobasal syndrome, striatal DAT binding positively correlated with the ipsilateral prefrontal perfusion and negatively with the contralateral precentral perfusion. In Richardson's syndrome, striatal DAT binding positively correlated with perfusion in the ipsilateral precentral cortex and basal ganglia. Machine learning showed that the combination of CBF and DAT was better for delineating PD from APS (area under the curve [AUC] = 0.87) than either CBF (0.67) or DAT (0.50) alone.In PD and four-repeat tauopathy, prefrontal perfusion was related to ipsilateral nigrostriatal dopaminergic function. This dual-tracer frontostriatal relationship may be effectively used as a diagnostic tool for delineating PD from APS. © 2022 International Parkinson and Movement Disorder Society.

Corticobasal degeneration (CBD) is the most common neuropathological substrate for clinically diagnosed corticobasal syndrome (CBS), while identifying CBD pathology in living individuals has been challenging. This study aimed to examine the capability of positron emission tomography (PET) to detect CBD-type tau depositions and neuropathological classification of CBS.Sixteen CBS cases diagnosed by Cambridge's criteria and 12 cognitively healthy controls (HCs) underwent PET scans withSixteen CBS cases consisted of two cases (13%) with amyloid and tau positivities indicative of Alzheimer's disease (AD) pathologies, 11 cases (69%) with amyloid negativity and tau positivity, and three cases (19%) with amyloid and tau negativities. Amyloid(-), tau(+) CBS cases showed increased retentions ofPET-based classification of CBS was in accordance with previous neuropathological reports on the prevalences of AD, non-AD tauopathies, and others in CBS. The current work suggests that

Background Diastolic retrograde flow in the descending aorta (DAo) may occur in the presence of atherosclerosis and may be overlooked as a mechanism of retrograde embolization in patients with stroke. We performed thoracic endovascular aortic repair (TEVAR) in a patient with recurrent cerebral infarctions for treatment of aortic aneurysm with atheromatic plaque, which was considered as the source of embolism. Case presentation A 56-year-old man with a history of idiopathic thrombocytopenia and hypertension was referred to our hospital with paralysis of the right upper and lower limbs. Multiple cerebral infarctions were found and treated; however, 1 month later, another cerebral infarction developed. A small saccular aortic aneurysm with plaque was found beyond the left subclavian artery, and this site was deemed as the source of embolism. We performed TEVAR to prevent further recurrence of cerebral infarctions. No cerebral infarctions were observed 6 months post-operation. Conclusions TEVAR is a useful treatment for not only aortic aneurysm and dissection, but also cerebral infarctions caused by an embolic source proximal to the DAo due to retrograde aortic blood flow.

Excitatory neurons are preferentially impaired in early Alzheimer’s disease but the pathways contributing to their relative vulnerability remain largely unknown. Here we report that pathological tau accumulation takes place predominantly in excitatory neurons compared to inhibitory neurons, not only in the entorhinal cortex, a brain region affected in early Alzheimer’s disease, but also in areas affected later by the disease. By analyzing RNA transcripts from single-nucleus RNA datasets, we identified a specific tau homeostasis signature of genes differentially expressed in excitatory compared to inhibitory neurons. One of the genes, BCL2 associated athanogene 3BAG3, a facilitator of autophagy, was identified as a hub or master regulator, gene. We verified that reducing BAG3 levels in primary neurons exacerbated pathological tau accumulation whereas overexpression attenuated it. These results support the conclusion that tau homeostasis underlies the cellular and regional vulnerability of excitatory neurons to tau pathology., Life Science Reporting Summary Further information on research design is available in the Nature Research Reporting Summary linked to this article.

Background Subthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for alleviating motor symptoms in advanced Parkinson's disease (PD) patients; however, a postoperative decline in cognitive and speech function has become problematic although its mechanism remains unclear. The aim of the present study was to elucidate the properties of language and drawing ability and cerebral perfusion in PD patients after bilateral STN DBS surgery. Methods Western aphasia battery, including drawing as a subcategory, and perfusion (N-isopropyl-p-[123I] iodoamphetamine) SPECT scan was conducted in 21 consecutive PD patients , before, and three to six months after, bilateral STN DBS surgery while on stimulation. Perfusion images were compared with those of 17 age- and gender-matched healthy volunteers. In the parametric image analysis, the statistical peak threshold was set at P Results Although motor symptoms were improved and general cognition was preserved in the patient group, 11 patients (52.4%) showed a decline in the drawing subcategory after surgery, which showed a reduction in Frontal Assessment Battery score in this group of patients. Statistical parametric analysis of the brain perfusion images showed a decrease of cerebral blood flow in the prefrontal and cingulate cortex after surgery. Patients whose drawing ability declined showed decreased perfusion in the middle cingulate cortex comparing before and after surgery. Conclusion Present results show that some PD patients show a decline in drawing ability after bilateral STN DBS which may attributable by dysfunction in the cingulate network.

Brain-derived neurotrophic factor (BDNF), a neurotrophin, is known to promote neuronal differentiation stimulating neurite outgrowth in the developing CNS, and is also known to modulate synaptic plasticity, thereby contributing to learning and memory in the mature brain. Here, we investigated the role of increased levels of intracerebral BDNF in learning and memory function. Using genetically engineered transgenic BDNF overexpressing mice (RTG-BDNF), young adult, homozygous (+/+), heterozygous (+/-), or wild-type (-/-) littermates, we analyzed escape latency to a hidden-platform and swimming velocity in the Morris Water Maze test (MWM) with modifications for the mice. The MWM comprised 4 trials per day over 5 consecutive days (sessions) without prior or subsequent training. In a separate set of animals, BDNF protein levels in the cortex, thalamostriatum and the hippocampus were measured quantitatively using ELISA. In the BDNF (+/-) mice, the BDNF levels in the cortex, the thalamostriatum and the hippocampus were significantly high, compared to the wild-type littermates; 238%, 158%, and 171%, respectively (P

Development of a safe method to increase brain-derived neurotrophic factor (BDNF) in the brain is expected to have utility in enhancing learning and memory, in protecting the brain, and in suppressing appetite. We investigated the effects of whole-body exposure to high voltage electric potential (HELP), which generates an electric field and current density in the body, on BDNF levels in the brain, spatial learning, or resistance to cerebral infarction development after focal ischemia. Adult mice (C57BL/6J) were exposed to 3.5 kV, or 5.8 kV for 5 h a day, making indirect contact with the ground via room air, over 1, 3, 6 or 12 consecutive weeks. After treatment, BDNF levels, performances in the Morris water maze task (MWM), or development of infarct lesion after focal ischemia was analyzed. Treatment with 3.5 kV for 1, 3, 6 or 12 weeks, or with 5.8 kV for 1, 3 or 12 weeks increased BDNF levels in the cortex (P

Functionalization of nanoparticles and immobilization of biomolecules on nanoparticles are important techniques for various applications in biotechnology. For application in the biomedical field, the surface of ultradispersed diamond (UDD) is immobilized with amino-terminated DNA after functionalizing carboxylic or amino group on the UDD surface. The characterized surface of UDD, carboxylated UDD, and aminated UDD were analyzed by DRIFT spectroscopy. In addition, hybridization with Cy-5 labeled target DNA was clearly observed on functionalized UDD by fluorescence microscopy.

Fertilizable mammalian oocytes are arrested at the second meiotic metaphase (mII) by the cyclinB-Cdc2 heterodimer, maturation promoting factor (MPF). MPF is stabilized via the activity of an unidentified cytostatic factor (CSF), thereby suspending meiotic progression until fertilization. We here present evidence that a conserved 71 kDa mammalian orthologue of Xenopus XErp1/Emi2, which we term endogenous meiotic inhibitor 2 (Emi2) is an essential CSF component. Depletion in situ of Emi2 by RNA interference elicited precocious meiotic exit in maturing mouse oocytes. Reduction of Emi2 released mature mII oocytes from cytostatic arrest, frequently inducing cytodegeneration. Mos levels autonomously declined to undetectable levels in mII oocytes. Recombinant Emi2 reduced the propensity of mII oocytes to exit meiosis in response to activating stimuli. Emi2 and Cdc20 proteins mutually interact and Cdc20 ablation negated the ability of Emi2 removal to induce metaphase release. Consistent with this, Cdc20 removal prevented parthenogenetic or sperm-induced meiotic exit. These studies show in intact oocytes that the interaction of Emi2 with Cdc20 links activating stimuli to meiotic resumption at fertilization and during parthenogenesis in mammals.

application/pdf, テクニカルレポート, ソフトウェアシステムの開発において要求者と開発者の意思疎通を図るためにはオブジェクト指向によるプロトタイピングが有効である. しかし, 分析や設計段階で用いたオブジェクト指向パラダイムの種々の概念を実装段階で素直に記述できるオブジェクト指向言語は少ない. 本研究では, 動的振舞いや種々の関係を柔軟に記述でき, 一貫したオブジェクト指向開発を可能とするモデル記述言語Brambleを開発した. 本言語は, 全ての要素をオブジェクトとして扱い, コピーベースのオブジェクト指向を核とするインタプリタ言語である. また, オブジェクトはメソッドと変数を区別しない属性だけを持ち, 文字列だけを基本データ型とする. さらに, 言語処理系自体を開発環境やCASE環境と拡張できるように, グラフィックスインタフェースやデータベースインタフェースの機能をもつオブジェクトも基本オブジェクトとして持たせている., In a software system development, a prototyping with object-oriented paradjgm is useful for the better understanding between requirers and developers. Most of the current object-oriented programming languages can't represent thc oncepts of models in object-oriented analysis and design well. This paper presents a model description language: Bramble which represents the dynamic behaviors of an object and the flexible relationships between objects. Bramble's characteristics are to treat every element as an object, to be copy-based object-orientation, to have attributes not to distinguish methods and variables, and to have an only data type as a string. Furthermore, Bramble includes the several base objects that work as the interfaces of graphics and database in order to extend the interpreter to the development or CASE environment.

MSCoating is a new coating technology using pulse discharge. This coating technology, which is developed by Mitsubishi Electric and IHI, has been put into practical use as an anti-wear coating for low-pressure turbine blades in aero engines. Normally, Z-notch, which is the edge of a low-pressure turbine blade in an aero engine, is treated with anti-wear coating by welding because these edges are frictioned together while the engine is running. However, coating by welding requires pre-heating, removal of excess thickness and advanced skill to ensure high reliability. Therefore, improvement of productivity and cost reduction are required for the anti-wear coating of Z-notch. MSCoating is an innovative coating technology that is able to meet these requirements. MSCoating can eliminate the above processing needed for coating by welding, and has superb productivity and reliability for machine work. It is confirmed that anti-wear performance of the coating formed by MSCoating is about 10 times as high as that formed by welding in a fretting wear test under conditions similar to the real operating condition. It is suggested that hard precipitate such as carbide and oxide of chrome and cobalt oxide in the MSCoating layer play a role in the advantages of the anti-wear performance.

Background and Purpose— New immature neurons appear out of the germinative zone, in cortical Layers V to VI, after induced spreading depression in the adult rat brain. Because neural progenitors have been isolated in the cortex, we set out to determine whether a subgroup of mature cells in the adult cortex has the potential to divide and generate neural precursors. Methods— We examined the expression of endogenous markers of mitotic activity, proliferating cell nuclear antigen, and vimentin as a marker for neuronal progenitor cells, if any, in the adult rat cortex after spreading depression stimulation. Immunohistochemical analysis was also performed using antibodies for proliferating cell nuclear antigen, for vimentin, and for nestin. Nestin is a marker for activity dividing neural precursors. Results— At the end of spreading depression (Day 0), glial fibrillary acidic protein-positive cells in the subpial zone and cortical Layer I demonstrated increased mitotic activity, expressing vimentin and nestin. On Day 1, nestin + cells were found spreading in deeper cortical layers. On Day 3, vimentin − /nestin + , neural precursor-like cells appeared in cortical Layers V to VI. On Day 6, new immature neurons appeared in cortical Layers V to VI. Induced spreading depression evokes cell division of astrocytes residing in the subpial zone, generating neural precursor-like cells. Conclusions— Although neural precursor-like cells found in cortical Layers V to VI might have been transferred from the germinative zone rather than the cortical subpial zone, astrocytic cells in the subpial zone may be potent neural progenitors that can help to reconstruct impaired central nervous system tissue. Special caution is required when observing or treating spreading depression waves accompanying pathological conditions in the brain.

The application of a homogeneous matrix (Denavit-Hartenberg Convention) to manipulator-equipped mobile robots can unify the movement expression of mobile robot and manipulator kinematics. This concept can be expected to enable enhanced operational efficiency for total system control. Proposed in this paper is a new guidance method for autonomous mobile robots operating on arbitrarily curved courses, using a homogeneous matrix system. We approximated an arbitrarily shaped course to circular arcs and straight lines to make easier to describe it by language as the objective course. The proposed guidance control method, based on the geometrical concept that a circular course with an infinitely long radius is equal to a straight course, is suited to these course variations. Results of actual driving experiments showed sufficiently practical performance by the proposed guidance method.

Mammalian metaphase II (mII) exit and embryogenesis are induced at fertilisation by a signal thought to come from the sperm protein,phospholipase C-zeta (PLCZ1). Meiotic progression can also be triggered without sperm, as in parthenogenesis, although the classic mouse in vivo parthenogenetic model, LT/Sv, fails in meiosis I owing to an unknown molecular etiology. Here, we dissect PLCZ1 specificity and function in vivo and address its ability to interfere with maternal meiotic exit. Wild-type mouse Plcz1 expression was restricted to post-pubertal testes and the brains of both sexes, with region-specifying elements mapping to a 4.1 kb Plcz1 promoter fragment. When broad ectopic PLCZ1 expression was forced in independent transgenic lines, they initially appeared healthy. Their oocytes underwent unperturbed meiotic maturation to mII but subsequently exhibited autonomous intracellular free calcium oscillations, second polar body extrusion, pronucleus formation and parthenogenetic development. Transfer of transgenic cumulus cell nuclei into wild-type oocytes induced activation and development, demonstrating a direct effect of PLCZ1 analogous to fertilisation. Whereas Plcz1 transgenic males remained largely asymptomatic, females developed abdominal swellings caused by benign ovarian teratomas that were under-represented for paternally- and placentally-expressed transcripts. Plcz1 was not overexpressed in the ovaries of LT/Sv or in human germline ovarian tumours. The narrow spectrum of PLCZ1 activity indicates that it is modulated by tissue-restricted accessory factors. This work characterises a novel model in which parthenogenesis and tumourigenesis follow full meiotic maturation and are linked to fertilisation by PLCZ1.

Background and Purpose— Status epilepticus and cerebral ischemia stimulate persistent neurogenesis in the adult brain, but both conditions cause neuronal damage. We determined whether spreading depression, a common epiphenomenon of these conditions, stimulates persistent neurogenesis. Methods— We analyzed the effect of KCl-induced spreading depression on persistent neurogenesis and the spatio-temporal distribution of cells exhibiting immunohistochemical markers for divided and early committed neurons (new neurons) in the adult rat brain. Results— After induction of spreading depression for 48 hours, the density of mitotic cells, divided cells, and new neurons in the subventricular zone increased at days 1 to 3, days 3 to 6, and day 6, respectively ( P P P Conclusions— Spreading depression has the potential to stimulate persistent neurogenesis or to produce ectopic new neuron-like cells.

Preconditioning the rat brain with spreading depression for 48 h induces potent ischemic tolerance (infarct tolerance) after an interval of 12-15 days, consequently reducing the infarcted lesion size in the acute phase following focal cerebral ischemia. However, persistence of the morphological and functional neuroprotection has not yet been proven. We tested whether tolerance-derived neuroprotection against focal cerebral ischemia persists or merely delays the progress of cerebral infarction. Prolonged spreading depression was induced in mice by placing a depolarized focus with intracerebral microinfusion of KCl for 24 h; after intervals of 3, 6, 9 or 12 days, temporary focal ischemia was imposed. In the analysis of the infarcted lesion volume 24 h after ischemia, groups with 6 or 9 day interval demonstrated significantly smaller lesion volume compared to time-matched vehicle control group (P=0.002). Significant reduction in cerebral infarction was also observed at the chronic phase, namely 14 days after ischemia (33% reduction) (P=0.021) accompanied with less severe neurological deficits (38% reduction) (P=0.020). Using this technique, we also investigated if the mice with targeted disruption of a single BDNF allele (heterozygous BDNF-deficient mice) can gain the same potency of tolerance as the wild mice. In the result on infarcted lesion volumes following temporary focal ischemia, potent tolerance developed in the wild type (35% reduction) (P=0.007) but not in the heterozygous BDNF-deficient mice (

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今日の本格的なビデオディスク時代の幕明けは, 1972年12月, アメリカのMCA社がHe-Neレーザビームを用いたDISCOVISION方式を完成し, その年の9月にオランダのフィリップス社がVLP方式を発表したころからと言える.その後, 1974年には両社の光学方式ビデオディスクシステムについての提携が行われ, 今日の非接触光学方式として一本化され, パイオニアはこの最も新しい方式を採用し, その上に独自の高度な精密加工技術と光学技術を加えることにより高次元の商品化を実現した.

To clarify the causes of SFD from the view-point of placental function, investigations were made on feto-maternal amino acid circumstances and on how cyclic AMP behaves in the placenta, particularly in relation to the transport of amino acid across the placenta. Amino acids were measured by gas liquid chromatography (hydrogen-flame ion detector), c-AMP by the binding protein method, adenyl cyclase activity by Krishna's method, and proteins by Lowry's method. Results show: (1) The levels of maternal amino acids were indistinctive between the SFD group and the normal pregnancy group. (2) The feto-maternal ratio of amino acid concentrations (f/m ratio) was lower in the SFD group than in the normal control. (3) The level of c-AMP in the placenta was lower in the SFD group than in the control. (4) The lower level of placental C-AMP in the SFD placenta seems partly attributable to the decreased adenyl cyclase activity. (5) There was a positive correlation (r=0.61) between the content of c-AMP in the placenta and the f/m ratio of amino acid concentrations. These findings suggest a decline in placental active transport of amino acids in SFD; adenyl cyclase and c-AMP in the placenta presumably play a key role in such course.

This paper deals with the thermal stress analysis of an infinite circular elastic cylinder heated on the surface axisymmetrically by heat sources, which move at a constant velocity in the axial direction. The underlying heat conduction problem, as well as the associated thermoelastic problem, is attacked with the aid of the exponential Fourier transform on the assumption that the cylinder is homogeneous and isotropic with respect to both its thermal and elastic response and that the temperature distribution of the surface is prescribed. The solutions for the temperature and stress distributions are obtained in the form of infinite integrals. Numerical examples, which are carried out for two specific distributions of the surface temperature, show a marked influence of the velocity of the heat sources on the distribution of the thermal stresses.

In pursuit of the probable relationship of cAMP to the placental active transport of amino acids as suggested by our previous human data, experiments were done in this study with dibutyryl cAMP and theophylline loaded in pregnant rats to examine the changes in level of 14C-lysine in the maternal liver, placenta and fetus. The results are: (1) Loading of dibutyryl cAMP had no effect on the uptake of 14C-lysine in the maternal liver, placenta or fetus, except that the correction of the values with its concentration in the maternal blood revealed only a slightly significant elevation in the value in each of them 30 min after the loading. (2) Loading of theophylline significantly increased the uptake of 14C-lysine in all these organs. (3) The content of cAMP in the placenta significantly increased with the loading of theophylline. These results have led the authors to believe that endogenous cAMP is significantly linked with the placental active transport of amino acids, though there is no apparent contribution to it by exogenous cAMP.