HIV-1 Nef limits communication between linker of activated T cells and SLP-76 to reduce formation of SLP-76-signaling microclusters following TCR stimulation

Signal initiation by engagement of the TCR triggers actin rearrangements, receptor clustering, and dynamic organization of signaling complexes to elicit and sustain downstream signaling. Nef, a pathogenicity factor of HIV, disrupts early TCR signaling in target T cells. To define the mechanism underlying this Nef-mediated signal disruption, we employed quantitative single-cell microscopy following surface-mediated TCR stimulation that allows for dynamic visualization of distinct signaling complexes as microclusters (MCs). Despite marked inhibition of actin remodeling and cell spreading, the induction of MCs containing TCR-CD3 or ZAP70 was not affected significantly by Nef. However, Nef potently inhibited the subsequent formation of MCs positive for the signaling adaptor Src homology-2 domain-containing leukocyte protein of 76 kDa (SLP-76) to reduce MC density in Nef-expressing and HIV-1-infected T cells. Further analyses suggested that Nef prevents formation of SLP-76 MCs at the level of the upstream adaptor protein, linker of activated T cells (LAT), that couples ZAP70 to SLP-76. Nef did not disrupt pre-existing MCs positive for LAT. However, the presence of the viral protein prevented de novo recruitment of active LAT into MCs due to retargeting of LAT to an intracellular compartment. These modulations in MC formation and composition depended on Nef's ability to simultaneously disrupt both actin remodeling and subcellular localization of TCR-proximal machinery. Nef thus employs a dual mechanism to disturb early TCR signaling by limiting the communication between LAT and SLP-76 and preventing the dynamic formation of SLP-76-signaling MCs.

A ‘Big Data’ Approach to Mapping the Australian Twittersphere

This chapter discusses the methodological aspects and empirical findings of a large-scale, funded project investigating public communication through social media in Australia. The project concentrates on Twitter, but we approach it as representative of broader current trends toward the integration of large datasets and computational methods into media and communication studies in general, and social media scholarship in particular. The research discussed in this chapter aims to empirically describe networks of affiliation and interest in the Australian Twittersphere, while reflecting on the methodological implications and imperatives of ‘big data’ in the humanities. Using custom network crawling technology, we have conducted a snowball crawl of Twitter accounts operated by Australian users to identify more than one million users and their follower/followee relationships, and have mapped their interconnections. In itself, the map provides an overview of the major clusters of densely interlinked users, largely centred on shared topics of interest (from politics through arts to sport) and/or sociodemographic factors (geographic origins, age groups). Our map of the Twittersphere is the first of its kind for the Australian part of the global Twitter network, and also provides a first independent and scholarly estimation of the size of the total Australian Twitter population. In combination with our investigation of participation patterns in specific thematic hashtags, the map also enables us to examine which areas of the underlying follower/followee network are activated in the discussion of specific current topics – allowing new insights into the extent to which particular topics and issues are of interest to specialised niches or to the Australian public more broadly. Specifically, we examine the Twittersphere footprint of dedicated political discussion, under the #auspol hashtag, and compare it with the heightened, broader interest in Australian politics during election campaigns, using #ausvotes; we explore the different patterns of Twitter activity across the map for major television events (the popular competitive cooking show #masterchef, the British #royalwedding, and the annual #stateoforigin Rugby League sporting contest); and we investigate the circulation of links to the articles published by a number of major Australian news organisations across the network. Such analysis, which combines the ‘big data’-informed map and a close reading of individual communicative phenomena, makes it possible to trace the dynamic formation and dissolution of issue publics against the backdrop of longer-term network connections, and the circulation of information across these follower/followee links. Such research sheds light on the communicative dynamics of Twitter as a space for mediated social interaction. Our work demonstrates the possibilities inherent in the current ‘computational turn’ (Berry, 2010) in the digital humanities, as well as adding to the development and critical examination of methodologies for dealing with ‘big data’ (boyd and Crawford, 2011). Out tools and methods for doing Twitter research, released under Creative Commons licences through our project Website, provide the basis for replicable and verifiable digital humanities research on the processes of public communication which take place through this important new social network.

海底沉积层中水合物成藏过程模拟

水合物成藏是一种动态演变过程，从生成和分解速度相对大小角度提出了天然气水合物的动态成藏理论；分析指出天然气水合物储层状态主要存在三种类型：成长型（包括渗透型与扩散型）、成熟型和消退型，必须结合经济型指标对这三种类型水合物藏进行开采可行性研究。 通过在自制的透明鼓泡反应釜内模拟气体迁移与水合物形成实验，解释了气体迁移对体系内传热与传质、溶解性质、过压等的影响因，进一步指出需要研究新的水合物相图。 从传热角度建立了水合物生长模型，计算并比较了南海北部陆坡琼东南盆地里甲烷水合物在渗漏系统和扩散系统下的生长速度，指出前者比后者快约20-40倍。 建立了水-气（游离气）-水合物-盐反应的多相流模型，演绎了在四个不同时刻随着水合物的形成，溶解度、渗透率、毛细压力、饱和度及盐度等的联动演变关系，并分析和比较了在沉积层水合物稳定区域内不同游离气饱和度和甲烷渗漏通量情况下水合物的形成过程和三种成藏类别。 反演了神狐海域水合物的形成，指出该区很可能是属于发育阶段的成长型渗漏系统水合物储藏，按照甲烷渗漏通量为0.5kg/m2·a计算，该地区已演化了约4800a，还需要约2700ka孔隙中水合物可到最大体积饱和度，达约75%，并在此后游离气将溢出沉积层进入海水中；计算得最终的甲烷水合物储量约为1.47×109m3，即该区最终将储存着约2200亿立方米甲烷气，是现在预测的约13倍！

Magnetic and mineralogical analyses of Ganzi and Luochuan sections

We present a first combined environmental magnetic and geochemical investigation of a loess-paleosol sequence (<55 ka) from the Chuanxi Plateau on the eastern margin of the Tibetan Plateau. Detailed comparison between the Ganzi section and the Luochuan section from the Chinese Loess Plateau (CLP) allows quantification of the effects of provenance and climate on pedogenic magnetic enhancement in Chinese loess. Rare earth element patterns and clay mineral compositions indicate that the Ganzi loess originates from the interior of the Tibetan Plateau. The different Ganzi and CLP loess provenances add complexity to interpretation of magnetic parameters in terms of the concentration and grain size of eolian magnetic minerals. Enhanced paleosol magnetism via pedogenic formation of ferrimagnetic nanoparticles is observed in both sections, but weaker ferrimagnetic contributions, finer superparamagnetic (SP) particles and stronger chemical weathering are found in the Ganzi loess, which indicates the action of multiple pedogenic processes that are dominated by the combined effects of mean annual precipitation (MAP), potential evapotranspiration (PET), organic matter and aluminium content. Under relatively high MAP and low PET conditions, high soil moisture favours transformation of ferrimagnetic minerals to hematite, which results in a relatively higher concentration of hematite but weaker ferrimagnetism of Ganzi loess. Initial growth of superparamagnetic (SP) particles is also documented in the incipient loess at Ganzi, which directly reflects the dynamic formation of nano-sized pedogenic ferrimagnets. A humid pedogenic environment with more organic matter and higher Al content also helps to form finer SP particles. We therefore propose that soil water balance, rather than solely rainfall, dominates the type, concentration and grain size of secondary ferrimagnetic minerals produced by pedogenesis.

Trafficking, Assembly, and Function of a Connexin43-Green Fluorescent Protein Chimera in Live Mammalian CellsV⃞

To examine the trafficking, assembly, and turnover of connexin43 (Cx43) in living cells, we used an enhanced red-shifted mutant of green fluorescent protein (GFP) to construct a Cx43-GFP chimera. When cDNA encoding Cx43-GFP was transfected into communication-competent normal rat kidney cells, Cx43-negative Madin–Darby canine kidney (MDCK) cells, or communication-deficient Neuro2A or HeLa cells, the fusion protein of predicted length was expressed, transported, and assembled into gap junctions that exhibited the classical pentalaminar profile. Dye transfer studies showed that Cx43-GFP formed functional gap junction channels when transfected into otherwise communication-deficient HeLa or Neuro2A cells. Live imaging of Cx43-GFP in MDCK cells revealed that many gap junction plaques remained relatively immobile, whereas others coalesced laterally within the plasma membrane. Time-lapse imaging of live MDCK cells also revealed that Cx43-GFP was transported via highly mobile transport intermediates that could be divided into two size classes of <0.5 μm and 0.5–1.5 μm. In some cases, the larger intracellular Cx43-GFP transport intermediates were observed to form from the internalization of gap junctions, whereas the smaller transport intermediates may represent other routes of trafficking to or from the plasma membrane. The localization of Cx43-GFP in two transport compartments suggests that the dynamic formation and turnover of connexins may involve at least two distinct pathways.

Modelo para formação dinâmica de rede de fornecedores em empresas estendidas

Supply chains have become an important focus for competitive advantage. The performance of a company increasingly depends on its ability to maintain effective and efficient relationships with its suppliers and customers. The extended enterprise (i.e. composed of several partners) needs to be dynamically formed in order to be agile and adaptable. According to the Digital Manufacturing paradigm, companies have to be able to quickly share and disseminate information regarding planning, designing and manufacturing of products. Additionally, they must be responsive to all technical and business determinants, as well as be assessed and certified for guaranteed performance. The current research intends to present a solution for the dynamic composition of the extended enterprise, formed to take advantage of market opportunities quickly and efficiently. A construction model was developed. This construction model consists of: information model, protocol model and process model. The information model has been defined based on the concepts of Supply Chain Operations Reference model (SCOR®). In this model is defined information for negotiating the participation of candidate companies in the dynamic establishment of a network for responding to a given demand for developing and manufacturing products, in seven steps as follows: request for information; request for qualification; alignment of strategy; request for proposal; request for quotation; compatibility of process; and compatibility of system. The protocol model has been elaborated and inspired in the OSI, this model provides a framework for linking customers and suppliers, indicates a sequence to be followed, in order to selecte companies to become suppliers. The process model has been implemented by means of process modeling according to the BPMN standard and, in turn, implemented as a web-based application that runs the process through its several steps, which uses forms to gather data. An application example in the context of the oil and gas industry is used for demonstrating the solution concept.

Computational fluid dynamic analysis of intracranial aneurysm bleb Formation (NS26P)

Purpose: The management of unruptured aneurysms remains controversial as treatment infers potential significant risk to the currently well patient. The decision to treat is based upon aneurysm location, size and abnormal morphology (e.g. bleb formation). A method to predict bleb formation would thus help stratify patient treatment. Our study aims to investigate possible associations between intra-aneurysmal flow dynamics and bleb formation within intracranial aneurysms. Competing theories on aetiology appear in the literature. Our purpose is to further clarify this issue. Methodology: We recruited data from 3D rotational angiograms (3DRA) of 30 patients with cerebral aneurysms and bleb formation. Models representing aneurysms pre-bleb formation were reconstructed by digitally removing the bleb, then computational fluid dynamics simulations were run on both pre and post bleb models. Pulsatile flow conditions and standard boundary conditions were imposed. Results: Aneurysmal flow structure, impingement regions, wall shear stress magnitude and gradients were produced for all models. Correlation of these parameters with bleb formation was sought. Certain CFD parameters show significant inter patient variability, making statistically significant correlation difficult on the partial data subset obtained currently. Conclusion: CFD models are readily producible from 3DRA data. Preliminary results indicate bleb formation appears to be related to regions of high wall shear stress and direct impingement regions of the aneurysm wall.

Computational fluid dynamic analysis of intracranial aneurysmal bleb formation

Background The management of unruptured aneurysms is controversial with the decision to treat influenced by aneurysm characteristics including size and morphology. Aneurysmal bleb formation is thought to be associated with an increased risk of rupture. Objective To correlate computational fluid dynamic (CFD) indices with bleb formation. Methods Anatomical models were constructed from three-dimensional rotational angiogram (3DRA) data in 27 patients with cerebral aneurysms harbouring single blebs. Additional models representing the aneurysm before bleb formation were constructed by digitally removing the bleb. We characterised haemodynamic features of models both with and without the bleb using CFDs. Flow structure, wall shear stress (WSS), pressure and oscillatory shear index (OSI) were analysed. Results There was a statistically significant association between bleb location at or adjacent to the point of maximal WSS (74.1%, p=0.019), irrespective of rupture status. Aneurysmal blebs were related to the inflow or outflow jet in 88.9% of cases (p<0.001) whilst 11.1% were unrelated. Maximal wall pressure and OSI were not significantly related to bleb location. The bleb region attained a lower WSS following its formation in 96.3% of cases (p<0.001) and was also lower than the average aneurysm WSS in 86% of cases (p<0.001). Conclusion Cerebral aneurysm blebs generally form at or adjacent to the point of maximal WSS and are aligned with major flow structures. Wall pressure and OSI do not contribute to determining bleb location. The measurement of WSS using CFD models may potentially predict bleb formation and thus improve the assessment of rupture risk in unruptured aneurysms.

Decision making in social neurobiological systems modeled as transitions in dynamic pattern formation

Extant models of decision making in social neurobiological systems have typically explained task dynamics as characterized by transitions between two attractors. In this paper, we model a three-attractor task exemplified in a team sport context. The model showed that an attacker–defender dyadic system can be described by the angle x between a vector connecting the participants and the try line. This variable was proposed as an order parameter of the system and could be dynamically expressed by integrating a potential function. Empirical evidence has revealed that this kind of system has three stable attractors, with a potential function of the form V(x)=−k1x+k2ax2/2−bx4/4+x6/6, where k1 and k2 are two control parameters. Random fluctuations were also observed in system behavior, modeled as white noise εt, leading to the motion equation dx/dt = −dV/dx+Q0.5εt, where Q is the noise variance. The model successfully mirrored the behavioral dynamics of agents in a social neurobiological system, exemplified by interactions of players in a team sport.

A new dynamic model for study of dislocation pattern formation

Based on the principle given in nonlinear diffusion-reaction dynamics, a new dynamic model for dislocation patterning is proposed by introducing a relaxation time to the relation between dislocation density and dislocation flux. The so-called chemical potential like quantities, which appear in the model can be derived from variation principle for free energy functional of dislocated media, where the free energy density function is expressed in terms of not only the dislocation density itself but also their spatial gradients. The Linear stability analysis on the governing equations of a simple dislocation density shows that there exists an intrinsic wave number leading to bifurcation of space structure of dislocation density. At the same time, the numerical results also demonstrate the coexistence and transition between different dislocation patterns.

Static and dynamic electric field domain formation in a doped GaAs/AlAs superlattice

We have observed the transition from static to dynamic electric field domain formation induced by a transverse magnetic field and the sample temperature in a doped GaAs/AlAs superlattice. The observations can be very well explained by a general analysis of instabilities and oscillations of the sequential tunnelling current in superlattices based solely on the magnitude of the negative differential resistance region in the tunnelling characteristic of a single barrier. Both increasing magnetic field and sample temperature change the negative differential resistance and cause the transition between static and dynamic electric field domain formation. (C) 2000 Elsevier Science B.V. All rights reserved.

Dynamic dc voltage band observed within each current branch in the transition from static to dynamic electric-field domain formation in a doped GaAs/AlAs superlattice

A dynamic dc voltage band was found emerging from each sawtooth-like branch of the current-voltage characteristics of a doped GaAs/AlAs superlattice in the transition process from static to dynamic electric-field domain formation caused by increasing the sample temperature. As the temperature increases, these dynamic dc voltage bands expand within each sawtooth-like branch, squeeze out the static regions, and join up together to turn the whole plateau into dynamic electric-field domain formation. These results are well explained by a general analysis of stability of the sequential tunneling current in superlattices. (C) 1999 American Institute of Physics. [S0003-6951(99)04443-5].

Static and dynamic electric field domain formation in a doped GaAs/AlAs superlattice

We have observed the transition from static to dynamic electric field domain formation induced by a transverse magnetic field and the sample temperature in a doped GaAs/AlAs superlattice. The observations can be very well explained by a general analysis of instabilities and oscillations of the sequential tunnelling current in superlattices based solely on the magnitude of the negative differential resistance region in the tunnelling characteristic of a single barrier. Both increasing magnetic field and sample temperature change the negative differential resistance and cause the transition between static and dynamic electric field domain formation. (C) 2000 Elsevier Science B.V. All rights reserved.