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In the autonomous driving era, automotive architecture has been rapidly progressing toward electronic control unit (ECU) integration and centralization. Advanced vehicle control is becoming increasingly important for safe driving. It requires microcontroller unit (MCU) integration, the highest automotive safety integrity level (ASIL), and network performance improvement. A 28-nm 600-MHz automotive flash MCU has been developed for next-generation automotive architecture. The MCU for vehicle control integrates three key features: a virtualization-assisted processor (VAP) for functional safety, a built-in self-test in the field (field-BIST) at a sleep resume (SR) BIST for functional safety, and a serial gigabit media independent interface (SGMII) for the in-vehicle network. The VAP helps the hypervisor to realize real-time virtualization to execute several different virtual machines without interference. The SR-BIST realizes random hardware failures per hour of 10−8 in various automotive applications. In the SGMII circuit, we used 5-V transistors for high reliability despite their narrow bandwidth. The automotive MCU satisfies the ISO26262 ASIL D system requirements with a low power consumption of 0.52 W. The VAP can realize the severe automotive control hard real time capability.

Pulmonary pleomorphic carcinoma (PPC) is resistant to anticancer drug treatment, outcomes are poor, and no standard therapy has been established. High PD-L1 expression has been found in PPCs, suggesting the possible efficacy of an immune checkpoint inhibitor (ICI) in cancer immunotherapy; however, this approach requires further investigation through case accumulation. Herein, we report a case of rapid recurrence and progression of PPC early after surgery in a 70-year-old male ex-smoker. Surgery was performed for lung cancer of the right lower lobe, and a pathological examination indicated primary PPC with high PD-L1 expression (tumor proportion score: 90%). Because systemic metastasis recurred only six weeks after surgery, nivolumab was administered as second-line treatment. Marked tumor regression was observed on imaging after three cycles, revealing a near complete response. Palliative radiotherapy was applied to the bone metastasis region for pain relief before nivolumab was administered. This case suggests that an ICI can have an effect on PPC and that the efficacy of ICIs may be enhanced by radiotherapy-induced abscopal effects.

Kawasaki disease (KD) is a common vasculitis disorder of childhood. It can sometimes complicate coronary artery aneurysms, and treatment is required depending on the condition of stenosis. A 20-year-old man was referred for surgery with a coronary artery aneurysm and stenosis in the left coronary artery as sequelae of KD. He had a surgical history of left pneumothorax and bullae remaining on the right lung. We simultaneously performed off-pump coronary artery bypass for coronary artery stenosis and bullectomy. Coronary artery aneurysms with KD complicated by pneumothorax are rare, and we treated them using one-stage surgery.

This paper describes a microcontroller combining a high-precision AFE and a 32bit controller for industrial sensing applications such as temperature control, recording, weighing, and force sensing. The MCU based on an RXv2 core with DSP and FPU can process complex computations to enable sensor measurements, controls, and communications. By employing the proposed PGA with auto-zeroing technique and chip implementation techniques, the high-precision AFE achieves 29nVrms RMS noise at 7.6 sps, 10 nV/°C offset drift, 0.74 ppm/°C gain drift, which meets the requirements for sensing applications. The MCU enables signals to be measured with better than 0.1% precision without calibration. The temperature measurement system was demonstrated, which indicates sufficient measurement accuracy.

The mm-wave radar is an indispensable component for autonomous driving. A continuous-time (CT) $\Delta\Sigma$ ADC is expected to be suitable for this application due to its high precision and wide bandwidth as well as inherent anti-aliasing effect. However, the stable performance of the ADC against excessive input and PVT variations is a primary issue for real products which has so far not been addressed sufficiently. Since a high OSR for a wide-band CT $\Delta\Sigma$ ADC requires a prohibitively high sampling rate, the higher-order noise shaping [1] needs to be applied instead. In addition, the MASH structure [2-3] is preferred due to its robustness against the instability caused by excessive input. However, since the analog transfer function of a CT MASH $\Delta\Sigma$ ADC is vulnerable to PVT variations, significant quantization-noise leakage occurs due to mismatch of the transfer function between analog and digital domains. Although the sturdy-MASH (SMASH) structure [4] can obviate the transfer-function matching on the first stage, it requires a zero-order second stage for sufficient matching on this stage, which needs to be compensated by a 4b quantizer and noise coupling [5]. Such design complication makes the PVT-robust operation of SMASH a critical issue.

Professor Masao Ito passed away in December last year at the age of 90. He not only performed great scientific achievements in the studies of the cerebellar circuit functions, but also made a great contribution to promotion of the neuroscience researches both in and outside Japan. His contribution includes foundation of the Japan Neuroscience Society, RIKEN Brain Science Institute, working as the president of International Brain Research Organization, foundation of Human Frontier Science Program and foundation of federation of scientific associations in Asia such as FAONS.

Chronic expanding hematoma (CEH) is a rare disease that can develop in any region of the body, but it most frequently develops in the thorax. When intrathoracic CEH is left untreated, gradually expanding hematoma can be life-threatening, leading to respiratory failure or hemoptysis. We encountered an 89-year-old man with cardiopulmonary arrest on arrival. He had been healthy, and it was unclear whether CEH had previously been detected. A very large mass was observed on chest computed tomography (CT), but the cause of death could not be determined. In the autopsy, this mass was identified as CEH and no malignant findings were noted. A fresh hemorrhage had occurred in the hematoma and perforated the bronchial lumen, which caused airway obstruction/asphyxia and resulted in sudden death. CEH should be suspected when a very large tumorous lesion occupying the entire hemithorax is observed on chest imaging, and it is important to recognize that sudden death can occur in the natural course of CEH.

text, 紀要論文 / Departmental Bulletin Paper

Synaptic plasticity provides a mechanism for learning and memory. For cerebellar motor learning, long-term depression (LTD) of synaptic transmissions from parallel fibers (PF) to Purkinje cells (PC) is considered the basis for motor learning, and deficiencies of both LTD and motor learning are observed in various gene-manipulated animals. Common motor learning sets, such as adaptation of the optokinetic reflex (OKR), the vestibular-ocular reflex (VOR), and rotarod test were used for evaluation of motor learning ability. However, results obtained from the GluA2-carboxy terminus modified knock-in mice demonstrated normal adaptation of the VOR and the OKR, despite lacking PF-LTD. In that report, induction of LTD was only attempted using one type of stimulation protocol at room temperature. Thus, conditions to induce cerebellar LTD were explored in the same knock-in mutants using various protocols at near physiological temperature. Finally, we found stimulation protocols, by which LTD could be induced in these gene-manipulated mice. In this study, a set of protocols are proposed to evaluate LTD-induction, which will more accurately allow examination of the causal relationship between LTD and motor learning. In conclusion, experimental conditions are crucial when evaluating LTD in gene-manipulated mice.

Automotive architecture has been rapidly progressing toward integration and centralization [1]. Integration of multiple electronic control units (ECUs) reduces vehicle weight by deleting the wire harness between ECUs and the cooperative control of multiple functions, resulting in energy savings. The power consumption of automotive MCUs must be single-digit Watts under thermal constraints, and many functions have to be squeezed into one MCU. Adoption of a 28nm process is necessary for speed, power and density, because a conventional 40nm embedded flash process is insufficient on these axes. Furthermore, the integration of ECUs also mixes software components with varying safety integrity levels in one MCU. Resource isolation is inevitable for functional safety to avoid latent faults. In the autonomous driving era, data size and performance requirements will increase owing to the number and complexity of sensors requiring fusion in real time. Fast networks within vehicles are vital. With the evolution of sensor fusion, information centralization, and control decentralization, automotive architectures have been progressing toward increased integration and centralization.

Significance The formation and dissolution of internal models of the human body occur in the cerebellum, and their logical organization is essential for normal motor learning. Here, we propose that the two known types of internal models, forward and inverse, are combined into one tandem model. We analyzed human motor learning, theoretically and experimentally, in a prism-adaptation hand-reaching task. Remarkably, the behavioral analyses and computational modeling converged to support the existence of a tandem model and reveal its unique features in cerebellum-based motor learning. For example, intentional misreaching induced covert learning in the tandem model. Finally, the tandem model was used to index the nature and degree of cerebellar damage in patients., In performing skillful movement, humans use predictions from internal models formed by repetition learning. However, the computational organization of internal models in the brain remains unknown. Here, we demonstrate that a computational architecture employing a tandem configuration of forward and inverse internal models enables efficient motor learning in the cerebellum. The model predicted learning adaptations observed in hand-reaching experiments in humans wearing a prism lens and explained the kinetic components of these behavioral adaptations. The tandem system also predicted a form of subliminal motor learning that was experimentally validated after training intentional misses of hand targets. Patients with cerebellar degeneration disease showed behavioral impairments consistent with tandemly arranged internal models. These findings validate computational tandemization of internal models in motor control and its potential uses in more complex forms of learning and cognition.

In February 2014, wild American bullfrog Lithobates catesbeianus tadpoles from an artificial pond in the Kyusyu region, Japan, presented with coelomic and subcutaneous edema and erythema within the skin. A pathological examination of 57 tadpoles of American bullfrogs in the region was conducted to evaluate the disease. Crystal deposition of varying degrees was found in the kidneys of 35 tadpoles (61.4%). The crystals were transparent, pleomorphic in shape, highly birefringent in polarized light, and arranged in a radial pattern within the renal tubular lumen. Using Alizarin Red S stain and liquid chromatography, these crystals were identified as calcium oxalate. Severe coelomic and subcutaneous edema was observed in 7 of these 35 tadpoles (20.0%). Ammonia levels in coelomic fluid were extremely elevated (>1000 µg dl(-1)) in 4 tadpoles examined. These findings suggest that oxalate deposition in kidneys causes metabolic disorder with renal nephropathy. The source of the oxalate could not be determined; however, the presence of calcium oxalates in pond sediments, as revealed by liquid chromatography, suggested that the deposition was most likely due to ingestion of oxalate materials from the environment. This is the first report of oxalate nephropathy in free-living amphibians.

We face two difficulties when applying ISO 26262[1] in the concept phase. ISO 26262 is the functional safety standard in the automobile field and requires strict safety requirements. Usually, it is not easy to divide requirements into safety parts and non-safety parts because they are closely connected with each other. That is, we have to perform two activities, functional development and functional safety activity, simultaneously. Other difficulty is a term item. From the definition, the item is a 'system 1.129 or array of systems to implement a function at the vehicle level'. In concept phase, we apply hazard analysis to an item, not system. The system definition comes after item definition and hazard analysis and risk assessment. So, it is hard to use the conventional methods e.g. Failure Mode and Effect Analysis FMEA and Fault Tree Analysis FTA.

While the cerebellum's role in motor function is well recognized, the nature of its concurrent role in cognitive function remains considerably less clear. The current consensus paper gathers diverse views on a variety of important roles played by the cerebellum across a range of cognitive and emotional functions. This paper considers the cerebellum in relation to neurocognitive development, language function, working memory, executive function, and the development of cerebellar internal control models and reflects upon some of the ways in which better understanding the cerebellum's status as a "supervised learning machine" can enrich our ability to understand human function and adaptation. As all contributors agree that the cerebellum plays a role in cognition, there is also an agreement that this conclusion remains highly inferential. Many conclusions about the role of the cerebellum in cognition originate from applying known information about cerebellar contributions to the coordination and quality of movement. These inferences are based on the uniformity of the cerebellum's compositional infrastructure and its apparent modular organization. There is considerable support for this view, based upon observations of patients with pathology within the cerebellum.

We investigated a unique microzone of the cerebellum located in folium-p (fp) of rabbit flocculus. In fp, Purkinje cells were potently excited by stimulation of the hypothalamus or mesencephalic periaqueductal gray, which induced defense reactions. Using multiple neuroscience techniques, we determined that this excitation was mediated via beaded axons of orexinergic hypothalamic neurons passing collaterals through the mesencephalic periaqueductal gray. Axonal tracing studies using DiI and biotinylated dextran amine evidenced the projection of fp Purkinje cells to the ventrolateral corner of the ipsilateral parabrachial nucleus (PBN). Because, in defense reactions, arterial blood flow has been known to redistribute from visceral organs to active muscles, we hypothesized that, via PBN, fp adaptively controls arterial blood flow redistribution under orexin-mediated neuromodulation that could occur in defense behavior. This hypothesis was supported by our finding that climbing fiber signals to fp Purkinje cells were elicited by stimulation of the aortic nerve, a high arterial blood pressure, or a high potassium concentration in muscles, all implying errors in the control of arterial blood flow. We further examined the arterial blood flow redistribution elicited by electric foot shock stimuli in awake, behaving rabbits. We found that systemic administration of an orexin antagonist attenuated the redistribution and that lesioning of fp caused an imbalance in the redistribution between active muscles and visceral organs. Lesioning of fp also diminished foot shock-induced increases in the mean arterial blood pressure. These results collectively support the hypothesis that the fp microcomplex adaptively controls defense reactions under orexin-mediated neuromodulation.

Long-term depression (LTD) of synaptic transmission from parallel fibers (PFs) to a Purkinje cell (PC) in the cerebellum has been considered to be a core mechanism of motor learning. Recently, however, discrepancies between LTD and motor learning have been reported in mice with a mutation that targeted the expression of PF-PC LTD by blocking AMPA-subtype glutamate receptor internalization regulated via the phosphorylation of AMPA receptors. In these mice, motor learning behavior was normal, but no PF-PC LTD was observed. We reexamined slices obtained from these GluA2 K882A and GluA2 Δ7 knockin mutants at 3-6 mo of age. The conventional protocols of stimulation did not induce LTD in these mutant mice, as previously reported, but surprisingly, LTD was induced using certain modified protocols. Such modifications involved increases in the number of PF stimulation (from one to two or five), replacement of climbing fiber stimulation with somatic depolarization (50 ms), filling a patch pipette with a Cs(+)-based solution, or extension of the duration of conjunction. We also found that intracellular infusion of a selective PKCα inhibitor (Go6976) blocked LTD induction in the mutants, as in WT, suggesting that functional compensation occurred downstream of PKCα. The possibility that LTD in the mutants was caused by changes in membrane resistance, access resistance, or presynaptic property was excluded. The present results demonstrate that LTD is inducible by intensified conjunctive stimulations even in K882A and Δ7 mutants, indicating no contradiction against the LTD hypothesis of motor learning.

Aim The feasibility of transdermal delivery of naloxone, an opioid antagonist, by anodal iontophoresis patches using Ag/AgCl electrodes was investigated. Methods To examine the effect of current strength, species variation and drug concentration on skin permeability of naloxone, in vitro skin permeation studies were performed using rat dorsal skin and porcine ear skin as the membrane. To determine in vivo transdermal absorption rate of naloxone, the iontophoretic patch system was applied to the dorsal skin of conscious rat with a constant current supply for 24 h. Results The in vitro steady-state skin permeation flux of naloxone current-proportionally (0–360 μA/cm 2 ) increased without significant differences between these two different skin types. The in vitro delivery rate through the porcine skin was found to be independent of the concentration of naloxone hydrochloride dehydrate in the donor patch over the range from 1 to 10% (w/v). In the in vivo pharmacokinetic study, plasma concentrations of naloxone steadily increased and sustained steady-state levels from 4 h to 24 h after the initiation of current application. In vivo steady-state transdermal absorption rates at 90 and 180 μA/cm 2 were 136 and 305 μg/h/cm 2 , respectively. Conclusion These results suggest that the transdermal delivery rates of naloxone by anodal iontophoresis are sufficient for the management of intoxication in opioid-overdosed patients.

There is no doubt that boron neutron capture therapy (BNCT) is a promising cancer therapy in the near future. At present, one of the severest problems to solve is monitoring of the treatment effect during neutron irradiation. It is known to be difficult in real time. So far, activation foils, small detectors and so on were used to measure the thermal neutron fluence in a certain place of the tumor. The dose distribution is thus estimated from the measured result and prediction with a transport code. In the present study, 478 keV gamma-rays emitted from the excited state of {sup 7}Li produced by {sup 10}B(n,α){sup 7}Li reaction are directly measured to realize real time monitoring of the treatment effect of BNCT. In this paper, the result of the feasibility study carried out using a Monte Carlo transport code is summarized. We used CdTe detectors with a quite narrow collimator to obtain a BNCT image keeping good spatial resolution. The intensity of capture gamma-rays of 2223 keV produced by {sup 1}H(n,γ){sup 2}H reaction is very much higher than that of 478 keV. We thus adjusted the detector efficiency by selecting an appropriate thickness so as to optimize the efficiency ratio between 478 and 2223 keV. From the result of the detector response calculation, in case of 20 mm thick CdTe detector with the collimator of 2 mm in diameter, sufficient net count of ∼1000 for 478 keV in 30 min. was realized. It means an efficient and high-resolution BNCT-SPECT image could be obtained. (author)

ダブルルーメンチューブを使用し，左主気管支膜様部に損傷を生じた症例を経験したので報告する．患者は74歳女性．左肺腫瘍の診断・治療目的で左S6区域切除術を行った．気管内挿管には左用35Frダブルルーメンチューブを用いた．閉胸前の水封試験にて肺門部背側からの気漏を認め，左主気管支膜様部の縦走する3cmの損傷を発見した．ダブルルーメンチューブによる気管支損傷として縫合修復を行った．術後の気管支内視鏡検査では感染徴候や狭窄は認めず，経過は良好であった．ダブルルーメンチューブによる気管支損傷は稀ではあるが重篤な合併症であり，文献的考察を加えて報告する．

To demonstrate chromosomal injuries associated with in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), sister chromatid exchange (SCE), an indicator of DNA damage, was investigated and the cytogenetic influence of embryonic manipulation on chromosomes of early embryos and offspring was investigated. SCE analysis was performed in early embryos and offspring obtained by IVF, ICSI, or in vivo fertilization (control). To label chromosomes of early embryos, the embryos were cultured in BrdU-supplemented medium for 2 cell cycles. For offspring, BrdU solution was repeatedly injected intraperitoneally. Chromosome samples prepared from the embryos and the bone marrow cells of offspring were stained by the Fluorescence plus Giemsa (FPG) method. In the IVF and ICSI groups, the rates of early development, implantation and offspring were lower than those in the control group. The SCE frequency of early embryos was significantly higher in the IVF and ICSI groups than in the control grou...

Ratonale Sometimes, pleural effusion accompanying an acute Mycoplasma pneumoniae infection or tuberculous pleurisy has similar analysis results. We report a case of tuberculous pleurisy which was initially diagnosed as acute M pneumoniae infection, which is of special interest because anti-Mycoplasma antibody results were positive, which served as a red herring. Patient concerns A 20-year-old woman visited the outpatient emergency romm of our hospital for chief complaints of high fever, dry cough, and pleuralgia persiting for 2 days. Since anti-mycoplasma antibody test results were positive, we treated acute M pneumoniae infection and drained her pleural effusion. The condition tended to improve, but on day 16 postadmission, the acid-fast bacterial culture of the pleural effusion was positive for Mycobacterium tuberculosis. Diagnoses Tuberculous pleurisy. Interventions After the diagnosis, the patient received antituberculous drugs. Outcomes She completed treatment with no noticeable adverse events, and the right pleural effusion disappered and diffuse right pleural thickening improved. Lessons Exudative pleural effusion with lymphocyte dominance and a high adenosine deaminase level in M pneumoniae infection have been reported. Even though the condition suggests acute M pneumoniae infection, clinicians should be aware that tuberculous pleurisy and M pneumoniae infection can share similar clinical features, and should understand the usefulness and limitations of the anit-Mycoplasma antibody test.

In this study, we generated mice lacking the gene for G-substrate, a specific substrate for cGMP-dependent protein kinase uniquely located in cerebellar Purkinje cells, and explored their specific functional deficits. G-substrate–deficient Purkinje cells in slices obtained at postnatal weeks (PWs) 10–15 maintained electrophysiological properties essentially similar to those from WT littermates. Conjunction of parallel fiber stimulation and depolarizing pulses induced long-term depression (LTD) normally. At younger ages, however, LTD attenuated temporarily at PW6 and recovered thereafter. In parallel with LTD, short-term (1 h) adaptation of optokinetic eye movement response (OKR) temporarily diminished at PW6. Young adult G-substrate knockout mice tested at PW12 exhibited no significant differences from their WT littermates in terms of brain structure, general behavior, locomotor behavior on a rotor rod or treadmill, eyeblink conditioning, dynamic characteristics of OKR, or short-term OKR adaptation. One unique change detected was a modest but significant attenuation in the long-term (5 days) adaptation of OKR. The present results support the concept that LTD is causal to short-term adaptation and reveal the dual functional involvement of G-substrate in neuronal mechanisms of the cerebellum for both short-term and long-term adaptation.