Protein secondary structure prediction can provide important information for protein 3D structure prediction and protein functions. Deep learning offers a new opportunity to significantly improve ...prediction accuracy. In this article, a new deep neural network architecture, named the Deep inception‐inside‐inception (Deep3I) network, is proposed for protein secondary structure prediction and implemented as a software tool MUFOLD‐SS. The input to MUFOLD‐SS is a carefully designed feature matrix corresponding to the primary amino acid sequence of a protein, which consists of a rich set of information derived from individual amino acid, as well as the context of the protein sequence. Specifically, the feature matrix is a composition of physio‐chemical properties of amino acids, PSI‐BLAST profile, and HHBlits profile. MUFOLD‐SS is composed of a sequence of nested inception modules and maps the input matrix to either eight states or three states of secondary structures. The architecture of MUFOLD‐SS enables effective processing of local and global interactions between amino acids in making accurate prediction. In extensive experiments on multiple datasets, MUFOLD‐SS outperformed the best existing methods and other deep neural networks significantly. MUFold‐SS can be downloaded from http://dslsrv8.cs.missouri.edu/~cf797/MUFoldSS/download.html.
Chemodynamic therapy (CDT), enabling selective therapeutic effects and low side effect, attracts increasing attention in recent years. However, limited intracellular content of H2O2 and acid at the ...tumor site restrains the lasting Fenton reaction and thus the anticancer efficacy of CDT. Herein, a nanoscale Co–ferrocene metal–organic framework (Co‐Fc NMOF) with high Fenton activity is synthesized and combined with glucose oxidase (GOx) to construct a cascade enzymatic/Fenton catalytic platform (Co‐Fc@GOx) for enhanced tumor treatment. In this system, Co‐Fc NMOF not only acts as a versatile and effective delivery cargo of GOx molecules to modulate the reaction conditions, but also possesses excellent Fenton effect for the generation of highly toxic •OH. In the tumor microenvironment, GOx delivered by Co‐Fc NMOF catalyzes endogenous glucose to gluconic acid and H2O2. The intracellular acidity and the on‐site content of H2O2 are consequently promoted, which in turn favors the Fenton reaction of Co‐Fc NMOF and enhances the generation of reactive oxygen species (ROS). Both in vitro and in vivo results demonstrate that this cascade enzymatic/Fenton catalytic reaction triggered by Co‐Fc@GOx nanozyme enables remarkable anticancer properties.
A cascade nanozyme, named Co–ferrocene, combined with glucose oxidase (Co‐Fc@GOx) is successfully constructed, presenting a unique cascade enzymatic/Fenton effect for promoted chemodynamic therapy. In this platform, the Co–ferrocene metal–organic framework (Co‐Fc NMOF) shows unique Fenton activity, and GOx molecules are delivered significantly and amplify the Fenton reaction. This study offers another potential therapeutic platform for synergetic cancer treatment.
This study sought to explore qualitatively experiences of existential loneliness (EL) in 80 older people living in retirement communities across the United Kingdom and Australia. Qualitative ...semi-structured interviews permitted in-depth exploration of issues such as biographical narrative, close relationships, loss, feelings of loneliness and retirement living. It was our intention to conduct a large-scale, deep-listening exercise that would provide further clues about EL in older people and the circumstances that give rise to such feelings. Data provided rich insight into older people's inner lives. Core themes identified loss of close attachments, lack of physical touch and intimacy, deterioration of health and body, and lack of an emotional language through which to express EL as central to older people's experiences. Furthermore, there was a suggestion that the move to retirement living was for many people inextricably connected to their experience of EL. Our data further support and extend the notion that EL can be thought of as a gradual sense of separation from the world and that ageing intensifies a myriad of social, emotional and physical circumstances that prompt its emergence. This sense of existential isolation need not be thought of as exclusive to those experiencing extreme frailty or who face death imminently – our data pointed to a clear and gradual emergence of EL throughout later life.
Shidu is a Chinese word, referring to a group of bereaved parents who were subject to the One-Child Policy and whose only child has died. Living in a society where care for older people largely ...relies on adult children, Shidu parents can be highly vulnerable due to losing an only child who may be their primary resource for old age security. Despite the noticeable rise of Shidu families in China, these vulnerable parents have often been overlooked in society and neglected by government policies. This article adopts a qualitative approach to analyse interviews with 15 older Shidu parents and four support professionals, capturing dynamic experiences of these parents’ vulnerability in grief, elderly care and end-of-life care. Through a sociological lens, these Shidu parents are found to have adapted, revised and even rejected the status quo to cope with significant gaps in support and to negotiate for more meaningful support for their old age. This dynamic but distressing picture has also revealed a lack of ongoing structures that can effectively address these older Shidu parents’ multifaceted and changing needs. Based on the findings, recommendations are made aiming to inform future practice and policymaking for older Shidu parents.
Protein disulfide isomerase (PDI) is the prototypic member of the thiol isomerase family that catalyses disulfide bond rearrangement. Initially identified in the endoplasmic reticulum as folding ...catalysts, PDI and other members in its family have also been widely reported to reside on the cell surface and in the extracellular matrix. Although how PDI is exported and retained on the cell surface remains a subject of debate, this unique pool of PDI is developing into an important mechanism underlying the redox regulation of protein sulfhydryls that are critical for the cellular activities under various disease conditions. This review aims to provide an overview of the pathophysiological roles of surface and extracellular PDI and their underlying molecular mechanisms. Understanding the involvement of extracellular PDI in these diseases will advance our knowledge in the molecular aetiology to facilitate the development of novel pharmacological strategies by specifically targeting PDI in extracellular compartments.
Recently, a series of innovative information-centric networking (ICN) architectures have been designed to better address the shift from host-centric end-to-end communication to requester-driven ...content retrieval. With the explosive increase of mobile data traffic, the mobility issue in ICN is a growing concern and a number of approaches have been proposed to deal with the mobility problem in ICN. Despite the potential advantages of ICN in mobile wireless environments, several significant research challenges remain to be addressed before its widespread deployment, including consistent routing, local cached content discovery, energy efficiency, privacy, security and trust, and practical deployment. In this paper, we present a brief survey on some of the works that have already been done to achieve mobile ICN, and discuss some research issues and challenges. We identify several important aspects of mobile ICN: overview, mobility enabling technologies, information-centric wireless mobile networks, and research challenges.
This paper presents a decision support system (DSS) for the modeling and management of project risks and risk interactions. This is a crucial activity in project management, as projects are facing a ...growing complexity with higher uncertainties and tighter constraints. Existing classical methods have limitations for modeling the complexity of project risks. For example, some phenomena like chain reactions and loops are not properly taken into account. This will influence the effectiveness of decisions for risk response planning and will lead to unexpected and undesired behavior in the project. Based on the concepts of DSS and the classical steps of project risk management, we develop an integrated DSS framework including the identification, assessment and analysis of the risk network. In the network, the nodes are the risks and the edges represent the cause and effect potential interactions between risks. The proposed simulation-based model makes it possible to re-evaluate risks and their priorities, to suggest and test mitigation actions, and then to support project manager in making decisions regarding risk response actions. An example of application is provided to illustrate the utility of the model.
► Present an integrated decision support system for project risk management. ► An interactions-based risk network model using advanced simulation. ► Address the limitations of current methods for modeling complexity in PRM. ► Provide a series of methods to model, analyze and control the risk network.
Background and Aim
Remimazolam tosilate (RT) is under evaluation as a sedative for endoscopic procedures. Herein, we aimed to evaluate safety including cognition recovery of RT administered in ...elderly patients undergoing upper gastrointestinal endoscopy and assess its safety dosage.
Methods
Ninety‐nine patients presenting for upper gastrointestinal endoscopy were randomized to receive 0.1 mg/kg RT (R1) or 0.2 mg/kg RT (R2), or propofol (P). Cognitive functions (memory, attention, and executive function) were measured via neuropsychological tests conducted before sedation and 5 min after recovery to full alertness. Adverse events were also assessed.
Results
There were no statistical differences between postoperative and baseline results for R1 group and P group, whereas those for R2 group revealed worsened postoperative cognitive functions (immediate recall and short delay recall) than baseline (P < 0.05). Compared with P group, Scores demonstrated worse restoration of immediate recall in R1 group, immediate recall, short‐delayed recall, and attention function in R2 group (P < 0.05). Patients in R2 group had a longer sedation time (12.09 vs 8.27 vs 8.21 min; P < 0.001) and recovery time (6.85 vs 3.82 vs 4.33 min; P < 0.001) than that in R1 group and P group. Moreover, the incidence of hypotension was 3.0% in R1 group, whereas it was 21.2% in R2 group and 48.5% in P group (P < 0.05).
Conclusion
The addition of 0.1 mg/kg RT as an adjunct to opiate sedation for upper gastrointestinal endoscopy not only achieves more stable perioperative hemodynamics but also achieves acceptable neuropsychiatric functions in elderly patients.
A simultaneously transmitting and reflecting surface (STARS) enabled edge caching system is proposed for reducing backhaul traffic and ensuring the quality of service. A novel Caching-at-STARS ...structure, where a dedicated smart controller and cache memory are installed at the STARS, is proposed to satisfy user demands with fewer hops and desired channel conditions. Then, a joint caching replacement and information-centric hybrid beamforming optimization problem is formulated for minimizing the network power consumption. As long-term decision processes, the optimization problems based on independent and coupled phase-shift models of Caching-at-STARS contain both continuous and discrete decision variables, and are suitable for solving with deep reinforcement learning (DRL) algorithm. For the independent phase-shift Caching-at-STARS model, we develop a frequency-aware based twin delayed deep deterministic policy gradient (FA-TD3) algorithm that leverages user historical request information to serialize high-dimensional caching replacement decision variables. For the coupled phase-shift Caching-at-STARS model, we conceive a cooperative TD3 & deep-Q network (TD3-DQN) algorithm comprised of FA-TD3 and DQN agents to decide on continuous and discrete variables respectively by observing the network external and internal environment. The numerical results demonstrate that: 1) The Caching-at-STARS-enabled edge caching system has advantages over traditional edge caching, especially in scenarios where Zipf skewness factors or cache capacity is large; 2) Caching-at-STARS outperforms the RIS-assisted edge caching systems; 3) The proposed FA-TD3 and cooperative TD3-DQN algorithms are superior in reducing network power consumption than conventional TD3.
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