The Development of the Concepts of prajñapti and nimitta: From the Bodhisattvabhūmi upto the Xian yang sheng jiao lun

The purpose of this paper is to show how the concepts of prajñapti (“the conventional designation”) and nimitta (“the causal basis”) have been developed in the Yogācāra school. In his Xian yang sheng jiao lun 顕揚聖教論VII 10, Asaṅga (ca. 330–405) formulates an argument to prove the existence of the dependent nature (paratantrasvabhāva) of things from the viewpoint of the Yogācāra theory. On the grounds that the conventional designation must have its causal basis, Asaṅga argues that there exists the dependent nature of things as it serves as the causal basis of the designation. The same idea is also expressed in the Tattvārtha Chapter 真実義品of the Bodhisattvabhūmi 菩薩地(ca. 230–300), which makes the point that a causal basis of the conventional designation is something that exists as a real entity (vastu). The idea refuted in both texts is that all the entities are the mere conventional designation (prajñaptimātram eva sarvam), which is quite often attributed to the Mādhyamika school. Furthermore, we notice that, in the Bodhisattvabhūmiviniścaya 摂決択分中菩薩地(ca. 350–380), a causal basis of the conventional designation is considered as that which arises in dependence on others (rten cing ’brel par ’byung ba). Accordingly, we may say that the concept of the causal basis, the germ of which is found in the Tattvārtha Chapter, is developed in the Bodhisattvabhūmiviniścaya and passed on to the Xian yang sheng jiao lun. Another point to notice is that the Mādhyamika scholar Bhāviveka (ca. 490–570), who criticizes the Yogācāra theory of the dependent nature by quoting the passage in question from the Xian yang sheng jiao lun, has in mind the arguments in the Tattvārtha Chapter. The idea Bhāviveka criticizes is that a causal basis of the conventional designation must be existent, which is commonly held by the Yogācāra scholars at that time.広島大学比較論理学プロジェクト研究センター研究成果報告書（2018年度）本研究は平成30年度一般財団法人仏教学術振興会研究助成を受けたものである

Bhāviveka’s Criticism of the Yogācāra’s Concepts of prajñapti and nimitta in the Madhyamakahṛdayakārikā and the Dasheng zhangzhen lun

The purpose of this paper is to show how the Mādhyamika scholar Bhāviveka (ca. 490–570) criticizes the Yogācāra’s concepts of prajñapti (“the conventional designation”) and nimitta (“the causal basis”). In his Xian yang sheng jiao lun 顕揚聖教論VII 10, Asaṅga (ca. 330–405) formulates an argument to prove the existence of the dependent nature (paratantrasvabhāva) of things from the viewpoint of the Yogācāra theory. On the grounds that the conventional designation must have its causal basis, Asaṅga argues that there exists the dependent nature of things as it serves as the causal basis of the designation. The same idea is also expressed in the Tattvārtha Chapter 真実義品of the Bodhisattvabhūmi 菩薩地(ca. 230–300), which makes the point that a causal basis of the conventional designation is something that exists as a real entity (vastu). The idea refuted in both texts is that all the entities are the mere conventional designation (prajñaptimātram eva sarvam), which is quite often attributed to the Mādhyamika school. The Mādhyamika scholar Bhāviveka, in the Madhyamakahṛdayakārikā and the Dasheng zhangzhen lun 大乗掌珍論, criticizes the Yogācāra’s idea that a causal basis of the conventional designation must be existent by quoting the passages in question from the Xian yang sheng jiao lun and the Bodhisattvabhūmi. According to Bhāviveka, an entity that arises dependently to others exists at conventional level. Since such entity serves as the causal basis of the designation, the Yogācāra’s idea in question should be refuted.広島大学比較論理学プロジェクト研究センター研究成果報告書（2020年度）本研究はJSPS科研費JP19J01490の助成を受けたものである

Detection of anticipatory postural adjustments prior to gait initiation using inertial wearable sensors

<p>Abstract</p> <p>Background</p> <p>The present study was performed to evaluate and characterize the potential of accelerometers and angular velocity sensors to detect and assess anticipatory postural adjustments (APAs) generated by the first step at the beginning of the gait. This paper proposes an algorithm to automatically detect certain parameters of APAs using only inertial sensors.</p> <p>Methods</p> <p>Ten young healthy subjects participated in this study. The subjects wore an inertial unit containing a triaxial accelerometer and a triaxial angular velocity sensor attached to the lower back and one footswitch on the dominant leg to detect the beginning of the step. The subjects were standing upright on a stabilometer to detect the center of pressure displacement (CoP) generated by the anticipatory adjustments. The subjects were asked to take a step forward at their own speed and stride length. The duration and amplitude of the APAs detected by the accelerometer and angular velocity sensors were measured and compared with the results obtained from the stabilometer. The different phases of gait initiation were identified and compared using inertial sensors.</p> <p>Results</p> <p>The APAs were detected by all of the sensors. Angular velocity sensors proved to be adequate to detect the beginning of the step in a manner similar to the footswitch by using a simple algorithm, which is easy to implement in low computational power devices. The amplitude and duration of APAs detected using only inertial sensors were similar to those detected by the stabilometer. An automatic algorithm to detect APA duration using triaxial inertial sensors was proposed.</p> <p>Conclusions</p> <p>These results suggest that the feasibility of accelerometers is improved through the use of angular velocity sensors, which can be used to automatically detect and evaluate APAs. The results presented can be used to develop portable sensors that may potentially be useful for monitoring patients in the home environment, thus encouraging the population to participate in more personalized healthcare.</p

Pharmacokinetics of Weekly Paclitaxel and Feasibility of Dexamethasone Taper in Japanese Patients with Advanced Non–small Cell Lung Cancer

AbstractPurposeWeekly paclitaxel combined with a platinum-based agent has been advocated as an alternative regimen for patients with advanced non–small cell lung cancer (NSCLC). Limited studies exist on the tolerability of weekly paclitaxel in Japanese patients with advanced NSCLC. Furthermore, the feasibility of dexamethasone taper in the premedication regimen for weekly paclitaxel has not been examined in these patients. To address this issue, we assessed the maximum tolerated dose, dose-limiting toxicity, and pharmacokinetics of weekly paclitaxel in Japanese patients with advanced NSCLC in a dose-escalation Phase I trial and examined the feasibility of dexamethasone taper in these patients.MethodsWeekly 1-hour infusions of paclitaxel were administered at doses of 80 to 120 mg/m2 (dose escalation of 20 mg/m2). The 7-week treatment cycle consisted of 6 infusions followed by a 2-week treatment interval. Pharmacokinetics were assessed during the first cycle. Dexamethasone was commenced at 16 mg and doses were successively halved if hypersensitivity reactions were absent.FindingsA total of 15 patients with either Stage IIIB or IV NSCLC were enrolled. Although no dose-limiting toxicity was observed at 120 mg/m2, 4 of 6 patients with peripheral neuropathy required discontinuation of treatment. The maximum accepted dose and the recommended dose were 120 and 100 mg/m2, respectively. No grade ≥3 adverse events were observed at 100 mg/m2. The maximum drug concentration and AUC correlated with dose escalation. The pharmacokinetic parameters after the first and sixth infusions were similar, indicating that repeated administration of paclitaxel did not result in drug accumulation or affect its pharmacokinetic profile. Partial response was observed in 3 of 15 patients. Plasma adrenocorticotropic hormone and cortisol levels decreased during treatment but approached baseline levels after a dexamethasone-free interval.ImplicationsWeekly paclitaxel at 100 mg/m2 given as a 1-hour infusion for 6 weeks followed by a 2-week treatment interval was well tolerated by Japanese patients with advanced NSCLC. Dexamethasone taper was feasible in these patients, and no clear trend in plasma adrenocorticotropic hormone or cortisol levels was observed

Glial Cell Lineage Expression of Mutant Ataxin-1 and Huntingtin Induces Developmental and Late-Onset Neuronal Pathologies in Drosophila Models

In several neurodegenerative disorders, toxic effects of glial cells on neurons are implicated. However the generality of the non-cell autonomous pathologies derived from glial cells has not been established, and the specificity among different neurodegenerative disorders remains unknown.We newly generated Drosophila models expressing human mutant huntingtin (hHtt103Q) or ataxin-1 (hAtx1-82Q) in the glial cell lineage at different stages of differentiation, and analyzed their morphological and behavioral phenotypes. To express hHtt103Q and hAtx1-82Q, we used 2 different Gal4 drivers, gcm-Gal4 and repo-Gal4. Gcm-Gal4 is known to be a neuroglioblast/glioblast-specific driver whose effect is limited to development. Repo-Gal4 is known to be a pan-glial driver and the expression starts at glioblasts and continues after terminal differentiation. Gcm-Gal4-induced hHtt103Q was more toxic than repo-Gal4-induced hHtt103Q from the aspects of development, locomotive activity and survival of flies. When hAtx1-82Q was expressed by gcm- or repo-Gal4 driver, no fly became adult. Interestingly, the head and brain sizes were markedly reduced in a part of pupae expressing hAtx1-82Q under the control of gcm-Gal4, and these pupae showed extreme destruction of the brain structure. The other pupae expressing hAtx1-82Q also showed brain shrinkage and abnormal connections of neurons. These results suggested that expression of polyQ proteins in neuroglioblasts provided a remarkable effect on the developmental and adult brains, and that glial cell lineage expression of hAtx1-82Q was more toxic than that of hHtt103Q in our assays.All these studies suggested that the non-cell autonomous effect of glial cells might be a common pathology shared by multiple neurodegenerative disorders. In addition, the fly models would be available for analyzing molecular pathologies and developing novel therapeutics against the non-cell autonomous polyQ pathology. In conclusion, our novel fly models have extended the non-cell autonomous pathology hypothesis as well as the developmental effect hypothesis to multiple polyQ diseases. The two pathologies might be generally shared in neurodegeneration

Structural basis of enzyme activity regulation by the propeptide of l-lysine α-oxidase precursor from Trichoderma viride

Harmuful proteins are usually synthesized as inactive precursors and are activated by proteolytic processing. l-Amino acid oxidase (LAAO) is a flavoenzyme that catalyzes the oxidative deamination of l-amino acid to produce a 2-oxo acid with ammonia and highly toxic hydrogen peroxide and, therefore, is expressed as a precursor. The LAAO precursor shows significant variation in size and the cleavage pattern for activation. However, the molecular mechanism of how the propeptide suppresses the enzyme activity remains unclear except for deaminating/decarboxylating Pseudomonasl-phenylalanine oxidase (PAO), which has a short N-terminal propeptide composed of 14 residues. Here we show the inactivation mechanism of the l-lysine oxidase (LysOX) precursor (prLysOX), which has a long N-terminal propeptide composed of 77 residues, based on the crystal structure at 1.97 Å resolution. The propeptide of prLysOX indirectly changes the active site structure to inhibit the enzyme activity. prLysOX retains weak enzymatic activity with strict specificity for l-lysine and shows raised activity in acidic conditions. The structures of prLysOX crystals that soaked in a solution with various concentrations of l-lysine have revealed that prLysOX can adopt two conformations; one is the inhibitory form, and the other is very similar to mature LysOX. The propeptide region of the latter form is disordered, and l-lysine is bound to the latter form. These results indicate that prLysOX uses a different strategy from PAO to suppress the enzyme activity and suggest that prLysOX can be activated quickly in response to the environmental change without proteolytic processing

Characteristics of systolic and diastolic potentials recorded in the left interventricular septum in verapamil-sensitive left ventricular tachycardia

We studied the electrophysiological characteristics of systolic (SP) and diastolic (DP) potentials recorded during sinus rhythm (SR) in the left interventricular septum of a 27 year-old woman presenting with verapamil-sensitive idiopathic left ventricular tachycardia (VT). During SR, and during VT, SP was activated from ventricular base-to-apex, and DP from apex-to-base. SP and DP were both detected at the site of successful ablation during SR, whereas during VT, DP was detected away from the earliest activation site. Thus, SP apparently reflected a critical component of the reentrant circuit, while DP reflected the activation of a bystander pathway

Quantitative evaluation of movement using the timed up-and-go test

藤元早鈴病院金沢大学理工研究域機械工学