Supersolvable closures of finitely generated subgroups of the free group

We prove the pro-supersolvable closure of a finitely generated subgroup of the free group is finitely generated. It extends similar results for pro-$p$ closures proved by Ribes-Zalesskii and pro-Nilpotent closures proved by Margolis-Sapir-Weil

CH-ILKBP regulates cell survival by facilitating the membrane translocation of protein kinase B/Akt

Cell survival depends on proper propagation of protective signals through intracellular signaling intermediates. We report here that calponin homology domain–containing integrin-linked kinase (ILK)–binding protein (CH-ILKBP), a widely expressed adaptor protein localized at plasma membrane-actin junctions, is essential for transmission of survival signals. Cells that are depleted of CH-ILKBP undergo extensive apoptosis despite the presence of cell–extracellular matrix contacts and soluble growth factors. The activating phosphorylation of protein kinase B (PKB/Akt), a key regulator of apoptosis, is impaired in the absence of CH-ILKBP. Importantly, loss of CH-ILKBP prevents the membrane translocation of PKB/Akt. Furthermore, forced membrane targeting of PKB/Akt bypasses the requirement of CH-ILKBP for the activating phosphorylation of PKB/Akt, suggesting that CH-ILKBP is required for the membrane translocation but not the subsequent phosphorylation of PKB/Akt. Finally, we show that loss of CH-ILKBP is also required for the full activation of extracellular signal–regulated kinase (ERK)1/2. However, restoration of the PKB/Akt activation is sufficient for protection of cells from apoptosis induced by the depletion of CH-ILKBP despite the persistent suppression of the ERK1/2 activation. Thus, CH-ILKBP is an important component of the prosurvival signaling pathway functioning primarily by facilitating the membrane translocation of PKB/Akt and consequently the activation of PKB/Akt in response to extracellular survival signals

Modulation of Actin Filament Dynamics by Inward Rectifying of Potassium Channel Kir2.1

Apart from its ion channel properties, the Kir2.1 channel has been found in tumors and cancer cells to facilitate cancer cell motility. It is assumed that Kir2.1 might be associated with cell actin filament dynamics. With the help of structured illumination microscopy (SIM), we show that Kir2.1 overexpression promotes actin filament dynamics, cell invasion, and adhesion. Mutated Kir2.1 channels, with impaired membrane expression, present much weaker actin regulatory effects, which indicates that precise Kir2.1 membrane localization is key to its actin filament remolding effect. It is found that Kir2.1 membrane expression and anchoring are associated with PIP2 affinity, and PIP2 depletion inhibits actin filament dynamics. We also report that membrane-expressed Kir2.1 regulates redistribution and phosphorylation of FLNA (filamin A), which may be the mechanism underlying Kir2.1 and actin filament dynamics. In conclusion, Kir2.1 membrane localization regulates cell actin filaments, and not the ion channel properties. These data indicate that Kir2.1 may have additional cellular functions distinct from the regulation of excitability, which provides new insight into the study of channel proteins

Generic Design Methodology for Smart Manufacturing Systems from a Practical Perspective, Part I—Digital Triad Concept and Its Application as a System Reference Model

Rapidly developed information technologies (IT) have continuously empowered manufacturing systems and accelerated the evolution of manufacturing system paradigms, and smart manufacturing (SM) has become one of the most promising paradigms. The study of SM has attracted a great deal of attention for researchers in academia and practitioners in industry. However, an obvious fact is that people with different backgrounds have different expectations for SM, and this has led to high diversity, ambiguity, and inconsistency in terms of definitions, reference models, performance matrices, and system design methodologies. It has been found that the state of the art SM research is limited in two aspects: (1) the highly diversified understandings of SM may lead to overlapped, missed, and non-systematic research efforts in advancing the theory and methodologies in the field of SM; (2) few works have been found that focus on the development of generic design methodologies for smart manufacturing systems from the practice perspective. The novelty of this paper consists of two main aspects which are reported in two parts respectively. In the first part, a simplified definition of SM is proposed to unify the existing diversified expectations, and a newly developed concept named digital triad (DT-II) is adopted to define a reference model for SM. The common features of smart manufacturing systems in various applications are identified as functional requirements (FRs) in systems design. To model a system that is capable of reconfiguring itself to adapt to changes, the concept of IoDTT is proposed as a reference model for smart manufacturing systems. In the second part, these two concepts are used to formulate a system design problem, and a generic methodology, based on axiomatic design theory (ADT), is proposed for the design of smart manufacturing systems

Generic Design Methodology for Smart Manufacturing Systems From a Practical Perspective. Part II—Systematic Designs of Smart Manufacturing Systems

In a traditional system paradigm, an enterprise reference model provides the guide for practitioners to select manufacturing elements, configure elements into a manufacturing system, and model system options for evaluation and comparison of system solutions against given performance metrics. However, a smart manufacturing system aims to reconfigure different systems in achieving high-level smartness in its system lifecycle; moreover, each smart system is customized in terms of the constraints of manufacturing resources and the prioritized performance metrics to achieve system smartness. Few works were found on the development of systematic methodologies for the design of smart manufacturing systems. The novel contributions of the presented work are at two aspects: (1) unified definitions of digital functional elements and manufacturing systems have been proposed; they are generalized to have all digitized characteristics and they are customizable to any manufacturing system with specified manufacturing resources and goals of smartness and (2) a systematic design methodology has been proposed; it can serve as the guide for designs of smart manufacturing systems in specified applications. The presented work consists of two separated parts. In the first part of paper, a simplified definition of smart manufacturing (SM) is proposed to unify the diversified expectations and a newly developed concept digital triad (DT-II) is adopted to define a generic reference model to represent essential features of smart manufacturing systems. In the second part of the paper, the axiomatic design theory (ADT) is adopted and expanded as the generic design methodology for design, analysis, and assessment of smart manufacturing systems. Three case studies are reviewed to illustrate the applications of the proposed methodology, and the future research directions towards smart manufacturing are discussed as a summary in the second part

Compatible Remediation on Vulnerabilities from Third-Party Libraries for Java Projects

With the increasing disclosure of vulnerabilities in open-source software, software composition analysis (SCA) has been widely applied to reveal third-party libraries and the associated vulnerabilities in software projects. Beyond the revelation, SCA tools adopt various remediation strategies to fix vulnerabilities, the quality of which varies substantially. However, ineffective remediation could induce side effects, such as compilation failures, which impede acceptance by users. According to our studies, existing SCA tools could not correctly handle the concerns of users regarding the compatibility of remediated projects. To this end, we propose Compatible Remediation of Third-party libraries (CORAL) for Maven projects to fix vulnerabilities without breaking the projects. The evaluation proved that CORAL not only fixed 87.56% of vulnerabilities which outperformed other tools (best 75.32%) and achieved a 98.67% successful compilation rate and a 92.96% successful unit test rate. Furthermore, we found that 78.45% of vulnerabilities in popular Maven projects could be fixed without breaking the compilation, and the rest of the vulnerabilities (21.55%) could either be fixed by upgrades that break the compilations or even be impossible to fix by upgrading.Comment: 11 pages, conferenc

CFTR Deficiency Affects Glucose Homeostasis via Regulating GLUT4 Plasma Membrane Transportation

Cystic Fibrosis (CF) is an autosomal recessive disorder caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. CF-related diabetes (CFRD) is one of the most prevalent comorbidities of CF. Altered glucose homeostasis has been reported in CF patients. The mechanism has not been fully elucidated. Besides the consequence of pancreatic endocrine dysfunction, we focus on insulin-responsive tissues and glucose transportation to explain glucose homeostasis alteration in CFRD. Herein, we found that CFTR knockout mice exhibited insulin resistance and glucose tolerance. Furthermore, we demonstrated insulin-induced glucose transporter 4 (GLUT4) translocation to the cell membrane was abnormal in the CFTR knockout mice muscle fibers, suggesting that defective intracellular GLUT4 transportation may be the cause of impaired insulin responses and glucose homeostasis. We further demonstrated that PI(4,5)P2 could rescue CFTR related defective intracellular GLUT4 transportation, and CFTR could regulate PI(4,5)P2 cellular level through PIP5KA, suggesting PI(4,5)P2 is a down-stream signal of CFTR. Our results revealed a new signal mechanism of CFTR in GLUT4 translocation regulation, which helps explain glucose homeostasis alteration in CF patients

Subaqueous tracks of marine tetrapods – indications to trackmakers based on new surfaces from the Middle Triassic of Guizhou Province, China

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