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关键词： Fenneropenaeus chinensis   Granular hemocytes   Hyalinocytes   WSSV   Binding proteins  

摘要： A number of white spot syndrome virus (WSSV)-binding proteins have been identified previously in the hemocytes of Fenneropenaeus chinensis. In order to further investigate the differential WSSV-binding proteins in hemocyte subpopulations, granular hemocytes and hyalinocytes were sorted from WSSV-infected shrimp by immunomagnetic bead (IMB) method. The results of ELISA and immuno-dot blot assay showed that the WSSV-binding activity of granular hemocytes proteins was much stronger than that of hyalinocytes proteins. And the percentage of WSSV-positive granular hemocytes was significantly higher than that of hyalinocytes post WSSV infection, indicating that granular hemocytes were more susceptible to WSSV infection. Moreover, a total of 9 WSSV-binding proteins were successfully identified in granular hemocytes and hyalinocytes by two-dimensional virus overlay protein binding assay (2D-VOPBA) and MALDI-TOF MS analysis, of which 3 binding proteins (arginine kinase, protease 1 and transglutaminase) existing in both hyalinocytes and granular hemocytes and 6 proteins (F(1)ATP synthase beta-chain, hnRNPs, GAPDH, RACK1, beta-actin and cellular retinoic acid) detected only in granular hemocytes. Among these identified WSSV-binding proteins, the transglutaminase (TG) was further recombinantly expressed, and the recombinant TG could be bound with WSSV. Subsequently, quantitative real-time PCR analysis showed that differential expression levels of WSSV-binding proteins were observed in granular hemocytes and hyalinocytes. The results of this study revealed that the WSSV-binding proteins were differentially expressed in granular hemocytes and hyalinocytes, which provided a deeper insight into the interaction between WSSV and hemocyte subpopulations.

关键词： Gradient flows   CAT spaces   Laplacian   Korevaar-Schoen energy  

摘要： We review the theory of Gradient Flows in the framework of convex and lower semi-continuous functionals on CAT(kappa)-spaces and prove that they can be characterized by the same differential inclusion y'(t)is an element of -partial derivative E-(y(t)) one uses in the smooth setting and more precisely that y'(t) selects the element of minimal norm in -partial derivative E-(y(t)). This generalizes previous results in this direction where the energy was also assumed to be Lipschitz. We then apply such result to the Korevaar-Schoen energy functional on the space of L-2 and CAT(0) valued maps: we define the Laplacian of such L-2 map as the element of minimal norm in -partial derivative E-(u), provided it is not empty. The theory of gradient flows ensures that the set of maps admitting a Laplacian is L-2-dense. Basic properties of this Laplacian are then studied.

关键词： 细胞工程  

ISBN: (纸本)9787564652074

摘要： 将微纳操控与组装技术与生物医学相结合, 开展细胞水平的捕获、分离等精确操作, 实现细胞多维组装并构建调节细胞生长的胞外环境。这对新药研发、生物传感器及离体神经网络接口等方面的具有重要意义, 在生物医学和临床医学等方面有着极为广泛的应用潜力。因此, 在本书中作者提出了一种基于光诱导数字掩模的细胞操作与多维组装方法, 在体外可控的构建细胞的胞外环境, 按照人的意愿实现细胞的精确操控和多维组装, 通过调节胞外的环境来研究细胞的行为学和获取细胞的多维信息, 从而建立多维细胞分析体系, 实现多维细胞信息获取, 为研究特定组织内细胞生理学和病理生理学行为提供全新的技术手段, 为揭示相关疾病的发病机制提供新的视角, 并为个性化药物筛选和生物传感研究提供新的途径。本书开展基于光诱导数字掩模的细胞操作与多维组装方法的研究, 旨在构建基于细胞多维信息的分析和研究体系, 为多维细胞操作与组装的体外实现提供一种新的方法和解决思路。

关键词： Neutral Equations   Difference Equations   Perturbed Boundary Control Systems   Regular Linear Systems   Feedback   Exponential Dichotomy  

摘要： This present paper is mainly devoted to investigate the property of spectral decomposition of neutral differential equations in infinite dimensional setting, that is the exponential dichotomy. In fact, we prove that the exponential dichotomy of the associated semigroup to such equations does not depend on that of their associated difference equations. Based on the regular linear systems and feedback theory, we introduce a new transformation of neutral-type equations which plays a key role in our investigation.

关键词： CBP   p300   metabolism   glycolysis   OXPHOS  

摘要： Simple Summary The coupling of metabolism with cellular status is critically important and highly evolutionarily conserved. However, how cells coordinate metabolism with transcription as they change their status is not clear. Utilizing multiomic and functional studies, we now demonstrate the dichotomous roles of the Kat3 coactivators CBP and p300 and, in particular, their extreme N-termini, in coordinating cellular metabolism with cell differentiation. Using multiple in vitro and in vivo systems, our study sheds new light on metabolic regulation in homeostasis and disease, including cancer. The integration of cellular status with metabolism is critically important and the coupling of energy production and cellular function is highly evolutionarily conserved. This has been demonstrated in stem cell biology, organismal, cellular and tissue differentiation and in immune cell biology. However, a molecular mechanism delineating how cells coordinate and couple metabolism with transcription as they navigate quiescence, growth, proliferation, differentiation and migration remains in its infancy. The extreme N-termini of the Kat3 coactivator family members, CBP and p300, by far the least homologous regions with only 66% identity, interact with members of the nuclear receptor family, interferon activated Stat1 and transcriptionally competent beta-catenin, a critical component of the Wnt signaling pathway. We now wish to report based on multiomic and functional investigations, utilizing p300 knockdown, N-terminal p300 edited and p300 S89A edited cell lines and p300 S89A knockin mice, that the N-termini of the Kat3 coactivators provide a highly evolutionarily conserved hub to integrate multiple signaling cascades to coordinate cellular metabolism with the regulation of cellular status and function.

关键词： p53   oligodendrocyte   inflammation   cuprizone   white matter stroke  

摘要： Promoting oligodendrocyte viability has been proposed as a therapeutic strategy for alleviating many neuronal diseases, such as multiple sclerosis and stroke. However, molecular pathways critical for oligodendrocyte survival under various stresses are still not well known. p53 is a strong tumor suppressor and regulates cell cycle, DNA repair and cell death. Our previous studies have shown that p53 plays an important role in promoting neuronal survival after insults, but its specific role in oligodendrocyte survival is not known. Here, we constructed the mice with oligodendrocyte-specific p53 loss by crossing TRP53(flox/flox) mice and CNP-cre mice, and found that p53 was dispensable for oligodendrocyte differentiation and myelin formation under physiological condition. In the experimental autoimmune encephalomyelitis (EAE) model, p53 loss of function, specifically in oligodendrocytes, did not affect the EAE disease severity and had no effect on demyelination in the spinal cord of the mice. Interestingly, p53 deficiency in oligodendrocytes significantly attenuated the demyelination of corpus callosum and alleviated the functional impairment of motor coordination and spatial memory in the cuprizone demyelination model. Moreover, the oligodendrocyte-specific loss of p53 provided protection against subcortical white matter damage and mitigated recognition memory impairment in mice in the white matter stroke model. These results suggest that p53 plays different roles in the brain and spinal cord or in response to various stresses. Thus, p53 may be a therapeutic target for oligodendrocyte prevention in specific brain injuries, such as white matter stroke and multiple sclerosis.

关键词： Acute myeloid leukemia   Acute lymphoblastic leukemia   Allogeneic hematopoietic cell transplantation   Disease status  

摘要： This study aimed to compare the effect of disease status at the time of allogeneic hematopoietic cell transplantation (HCT) on post-transplant outcomes between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Japanese nationwide registry data for 6901 patients with AML and 2469 patients with ALL were analyzed. In this study, 2850 (41%), 937 (14%), 62 (1%), and 3052 (44%) AML patients and 1751 (71%), 265 (11%), 23 (1%), and 430 (17%) ALL patients underwent transplantation in first complete remission (CR1), second CR (CR2), third or subsequent CR (CR3 +), and non-CR, respectively. The probabilities of overall survival at 5 years for patients transplanted in CR1, CR2, CR3 + , and non-CR were 58%, 61%, 41%, and 26% for AML patients and 67%, 45%, 20%, and 21% for ALL patients, respectively. Multivariate analyses revealed that the risks of relapse and overall mortality were similar for AML patients transplanted in CR1 and CR2 (P = 0.672 and P = 0.703), whereas they were higher for ALL patients transplanted in CR2 than for those transplanted in CR1 (P < 0.001 for both). The risks of relapse and overall mortality for those transplanted in CR3 + and non-CR increased in a stepwise manner for both diseases, with the relevance being stronger for ALL than for AML patients. These results suggest a significant difference in the effect of disease status at HCT on post-transplant outcomes in AML and ALL. Further investigation to incorporate measurable residual disease data is warranted.

关键词： Parkinson's disease   deep brain stimulation   functional MRI   fMRI   subthalamic nucleus   functional neurosurgery  

摘要： OBJECTIVE Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established neurosurgical treatment for the motor symptoms of Parkinson's disease (PD). While often highly effective, DBS does not always yield optimal therapeutic outcomes, and stimulation-induced adverse effects, including paresthesia, muscle contractions, and nausea/ lightheadedness, commonly occur and can limit the efficacy of stimulation. Currently, objective metrics do not exist for monitoring neural changes associated with stimulation-induced therapeutic and adverse effects. METHODS In the present study, the authors combined intraoperative functional MRI (fMRI) with STN DBS in 20 patients with PD to test the hypothesis that stimulation-induced blood oxygen level-dependent signals contained predictive information concerning the therapeutic and adverse effects of stimulation. RESULTS As expected, DBS resulted in blood oxygen level-dependent activation in myriad motor regions, including the primary motor cortex, caudate, putamen, thalamus, midbrain, and cerebellum. Across the patients, DBS-induced improvements in contralateral Unified Parkinson's Disease Rating Scale tremor subscores correlated with activation of thalamic, brainstem, and cerebellar regions. In addition, improvements in rigidity and bradykinesia subscores correlated with activation of the primary motor cortex. Finally, activation of specific sensorimotor-related subregions correlated with the presence of DBS-induced adverse effects, including paresthesia and nausea (cerebellar cortex, sensorimotor cortex) and unwanted muscle contractions (caudate and putamen). CONCLUSIONS These results suggest that DBS-induced activation patterns revealed by fMRI contain predictive information with respect to the therapeutic and adverse effects of DBS. The use of fMRI in combination with DBS therefore may hold translational potential to guide and improve clinical stimulator optimization in patients.

关键词： Partial differential equations   Option pricing   Kolmogorov operator  

摘要： We prove the existence and uniqueness of the fundamental solution for Kolmogorov operators associated to some stochastic processes, that arise in the Black & Scholes setting for the pricing problem relevant to path dependent options. We improve previous results in that we provide a closed form expression for the solution of the Cauchy problem under weak regularity assumptions on the coefficients of the differential operator. Our method is based on a limiting procedure, whose convergence relies on some barrier arguments and uniform a priori estimates recently discovered. (C) 2021 Elsevier Ltd. All rights reserved.

关键词： Differential mechanism   profile error   crowning design   interval analysis   least square method  

摘要： A differential mechanism is an essential component in the majority of automotive applications. Its vitality stems from the fact that it allows a wheel-drive vehicle to take a curve safely. On the other hand, it can ratchet up the vibration in the wheel-drive vehicle due to the excessive gear tooth deflection from applied torque. Some gear tooth modifications can increase or decrease the level of vibration in the mechanism. So far, very little attention has been paid to the effects of the uncertain geometric deviation of the tooth profile and uncertain crowning parameters on the dynamic performance of the mechanism. This study aims to investigate the impacts of these uncertain parameters on the gear systems' dynamic performance. To this end, the nonlinear interval model of the differential mechanism is proposed. The mesh stiffness for straight bevel gear is modelled through the potential energy method and slice theory, while bearing stiffness elements are calculated at each time step. A refined computational algorithm is proposed to deal with any gear system with multiple interval variables. The scanning method is used as a reference method in this paper. The main outcomes of this study are that the crowning design can slightly reduce the vibration in the mechanism, and the profile errors can increase its vibration level excessively. Besides, the results derived from the refined algorithm show similarities to those determined by the scanning method, and the study shows that the refined algorithm can handle any gear system with uncertain static or time-varying parameters.