Inhibition of protein misfolding and aggregation by natural phenolic compounds

Protein misfolding and aggregation into fibrillar deposits is a common feature of a large group of degenerative diseases affecting the central nervous system or peripheral organs, termed protein misfolding disorders (PMDs). Despite their established toxic nature, clinical trials aiming to reduce misfolded aggregates have been unsuccessful in treating or curing PMDs. An interesting possibility for disease intervention is the regular intake of natural food or herbal extracts, which contain active molecules that inhibit aggregation or induce the disassembly of misfolded aggregates. Among natural compounds, phenolic molecules are of particular interest, since most have dual activity as amyloid aggregation inhibitors and antioxidants. In this article, we review many phenolic natural compounds which have been reported in diverse model systems to have the potential to delay or prevent the development of various PMDs, including Alzheimer’s and Parkinson’s diseases, prion diseases, amyotrophic lateral sclerosis, systemic amyloidosis, and type 2 diabetes. The lower toxicity of natural compounds compared to synthetic chemical molecules suggest that they could serve as a good starting point to discover protein misfolding inhibitors that might be useful for the treatment of various incurable diseases.     

An Economic Model-Based Matching Approach Between Buyers and Sellers Through a Broker in an Open E-Marketplace

A broker in an open e-marketplace enables buyers and sellers to do business with each other. Although a broker plays an important role in e-marketplaces, theory and guidelines for matching between buyers and sellers in multi-attribute exchanges are limited. Therefore, a challenge for a broker’s responsibility is how to maximize a buyer’s total satisfaction degree as its goals under the consideration of trade-off between a buyer’s buying quantity and price paid to a seller, and other attributes. To solve this challenge, this paper proposes an economic model-based matching approach between a buyer’s requirements and a seller’s offers. The major contributions of this paper are that (i) a broker can model a seller’s price policy as per a buyer’s buying quantity through communication between a broker and a seller; (ii) due to each buyer’s different quantity demand, a broker models a buyer’s satisfaction degree as per a buyer’s buying quantity based on communication between a broker and a buyer; and (iii) to carry out a broker’s matching processes, an objective function and a set of constraints are generated to help a broker to maximize a buyer’s total satisfaction degree. Experimental results demonstrate the good performance of the proposed approach.     

Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs

Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response.     

ID-Based Public Auditing Protocol for Cloud Storage Data Integrity Checking with Strengthened Authentication and Security

Cloud storage service reduces the burden of data users by storing users’ data files in the cloud. But, the files might be modified in the cloud. So, data users hope to check data files integrity periodically. In a public auditing protocol, there is a trusted auditor who has certain ability to help users to check the integrity of data files. With the advantages of no public key management and verification, researchers focus on public auditing protocol in ID-based cryptography recently. However, some existing protocols are vulnerable to forgery attack. In this paper, based on ID-based signature technology, by strengthening information authentication and the computing power of the auditor, we propose an ID-based public auditing protocol for cloud data integrity checking. We also prove that the proposed protocol is secure in the random oracle model under the assumption that the Diffie-Hellman problem is hard. Furthermore, we compare the proposed protocol with other two ID-based auditing protocols in security features, communication efficiency and computation cost. The comparisons show that the proposed protocol satisfies more security features with lower computation cost.     

Approximation,Mad Men and the Death of JFK

In this article I take the US television series Mad Men (2007—present) as an exemplary ‘approximation’, a term I adopt to signal the way in which certain texts construct a changeable, fluid ‘truth’ resulting from collisions, exchange and dialectical argument. Approximations are layered, their formal layerings mirroring a layered, multifaceted argument. Mad Men integrates and represents real historical events within a fictional setting, and act that suggests that an event or action can never be finished, fixed and not open to reassessment. Specifically, this article examines ‘The Grown Ups’, Episode 12 of Season 3, which charts the events of 22 November 1963, the day Kennedy was assassinated. Although we might be able to bring to mind the images and conspiracy theories that have been made available since (such Abraham Zapruder’s 8 mm home movie footage of the assassination), these images were not available at the time. Mad Men as a series always strives to represent its historical milieu as authentically as possible, so the characters re-enact 22 November 1963 as authentically as possible by watching only what was on television that day (the news bulletin, Walter Kronkite’s announcement that Kennedy is dead). The contemporary backdrop to these events, including the resonances of ‘9/11’ through Mad Men, inform and collide with the authenticity on the screen.     

Cystic fibrosis transmembrane conductance regulator—emerging regulator of cancer

Mutations of cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis, the most common life-limiting recessive genetic disease among Caucasians. CFTR mutations have also been linked to increased risk of various cancers but remained controversial for a long time. Recent studies have begun to reveal that CFTR is not merely an ion channel but also an important regulator of cancer development and progression with multiple signaling pathways identified. In this review, we will first present clinical findings showing the correlation of genetic mutations or aberrant expression of CFTR with cancer incidence in multiple cancers. We will then focus on the roles of CFTR in fundamental cellular processes including transformation, survival, proliferation, migration, invasion and epithelial–mesenchymal transition in cancer cells, highlighting the signaling pathways involved. Finally, the association of CFTR expression levels with patient prognosis, and the potential of CFTR as a cancer prognosis indicator in human malignancies will be discussed.     

Bidirectional Feedback Dynamic Particle Filter with Big Data for the Particle Degeneracy Problem

Particle Filter(PF) is a data assimilation method to solve recursive state estimation problem which does not depend on the assumption of Gaussian noise, and is able to be applied for various systems even with non-linear and non-Gaussian noise. However, while applying PF in dynamic systems, PF undergoes particle degeneracy,sample impoverishment, and problems of high computational complexity. Rapidly developing sensing technologies are providing highly convenient availability of real-time big traffic data from the system under study like never before. Moreover, some sensors can even receive control commands to adjust their monitoring parameters. To address these problems, a bidirectional dynamic data-driven improvement framework for PF(B3 DPF) is proposed.The B3 DPF enhances feedback between the simulation model and the big traffic data collected by the sensors,which means the execution strategies(sensor data management, parameters used in the weight computation,resampling) of B3 DPF can be optimized based on the simulation results and the types and dimensions of traffic data injected into B3 DPF can be adjusted dynamically. The first experiment indicates that the B3 DPF overcomes particle degeneracy and sample impoverishment problems and accurately estimates the state at a faster speed than the normal PF. More importantly, the new method has higher accuracy for multidimensional random systems.In the rest of experiments, the proposed framework is applied to estimate the traffic state on a real road network and obtains satisfactory results. More experiments can be designed to validate the universal properties of B3 DPF.     

Quantitative Analysis of Multi-Recovery-Based Intrusion Tolerance Model

Quantitative analysis has always been a difficult problem in security analysis of intrusion tolerance systems. An intrusion tolerance model based on multiple recovery mechanisms is introduced in this paper and how to quantify the security attributes of the model is proposed. A state transition model with recovery states more accurately describes the dynamic behavior of the system. Considering that recovery mechanisms have a great impact on the security performance of the system, we set up the cost models corresponding to different recovery mechanisms. We propose a feasible security measure based on mean cost to security failure in order to evaluate the system cost during the recovery phase. The experimental results confirmed the feasibility of the proposed methods.     

Quantum Theory and the Nature of Consciousness

Our interest focusses on the idea, that consciousness is a powerful acting entity. Up to now there does not exist a scientific concept for this idea. This is not due to problems within the field of psychology or brain research, but rather in resisting theories of modern physics. That is, why we have to search for a solution in the field of physics. A solution can be found in a new understanding of the basics of physical theory. That could be given by abstract and absolute quantum bits of information (AQI bits). To avoid the popular misunderstanding of “information” as “meaningful” it was necessary to find a new word for the free-of-meaning AQI bits: the AQI bits establish a quantum pre-structure termed “Protyposis” (Greek: “pre-formation”), out of which real objects can be formed, starting from energetical and material elementary particles. The Protyposis AQI bits provide a pre-structure for all entities in natural sciences. They are the basic entities, whereof the physical nature of the brain, on the one hand, and the mental nature of consciousness, on the other hand, were formed during the cosmological and the following biological evolution. A deeper understanding of quantum structures may help to overcome the resistance against quantum theory in the field of brain research and consciousness. The key for an understanding is the concept of Protyposis, which means an abstract quantum information free of any definite meaning. With the AQI bits of the Protyposis, both, massless and massive quantum particles can be constructed. Even quantum information with special meanings, in example grammatically formulated thoughts, eventually could be explained. As long as the fundamental basis of quantum theory is misunderstood as being formed by a manifold of some small objects like atoms, quarks, or strings, the problem of understanding consciousness has no solution. If instead we understand quantum theory as based on truly simple quantum structures, there would be no longer fundamental problems for an understanding of consciousness.     

大传统与小传统:明清时期鲁西地区的碧霞元君信仰

明清时期鲁西地区是碧霞元君信仰极为盛行的地区,呈现出庙宇数量众多、分布地域广泛等特征.地方官员和士绅对碧霞元君信仰大多持默许和认可态度,并试图借助祀神活动传达官方祭祀理念,进行社会教化.地方官员和士绅关于泰山碧霞元君信仰的不同态度,反映了他们对于地方社会道德秩序的关注,表达了他们试图用官方正统文化去改造民间文化的强烈愿望.相较地方官员和士绅,普通民众崇祀神灵的目的则较为简单,带有显著的世俗性和功利性的特征.在满足其自身信仰需求同时,神灵信仰也起到了增强社会凝聚力、强化地域认同的作用.地方家族也利用重修庙貌、祭祀神灵等手段,实现庙宇与宗族的结合,以此达到增强家族凝聚力和认同感的目的.基于各自不同的目的和需要,官员、士绅和民众共同参与到信仰活动之中,使得信仰在地方社会不断得以延续和传承.