Vaginal delivery of the recombinant HIV-1 clade-C trimeric gp140 envelope protein CN54gp140 within novel rheologically structured vehicles elicits specific immune responses

Rheologically structured vehicle (RSV) gels were developed as delivery systems for vaginal mucosal vaccination with an HIV-1 envelope glycoprotein (CN54gp140). RSVs comprised a mucoadhesive matrix forming and vaginal fluid absorbing polymer. The mucoadhesive and rheological properties of the RSVs were evaluated in vitro, and the distribution, antigenicity and release of CN54gp140 were analysed by ELISA. CN54gp140 was uniformly distributed within the RSVs and continuously released in vitro in an antigenically intact form over 24 h. Vaginal administration to rabbits induced specific serum IgG, and IgG and IgA in genital tract secretions. The RSVs are a viable delivery modality for vaginal immunization.

An extended framework for evidential reasoning systems.

Use of the Dempster-Shafer (D-S) theory of evidence to deal with uncertainty in knowledge-based systems has been widely addressed. Several AI implementations have been undertaken based on the D-S theory of evidence or the extended theory. But the representation of uncertain relationships between evidence and hypothesis groups (heuristic knowledge) is still a major problem. This paper presents an approach to representing such knowledge, in which Yen’s probabilistic multi-set mappings have been extended to evidential mappings, and Shafer’s partition technique is used to get the mass function in a complex evidence space. Then, a new graphic method for describing the knowledge is introduced which is an extension of the graphic model by Lowrance et al. Finally, an extended framework for evidential reasoning systems is specified.

Immune activation in Retinal Aging: A Gene Expression Study.

PURPOSE
To investigate changes in gene expression during aging of the retina in the mouse.

METHODS
Total RNA was extracted from the neuroretina of young (3-month-old) and old (20-month-old) mice and processed for microarray analysis. Age-related, differentially expressed genes were assessed by the empiric Bayes shrinkagemoderated t-statistics method. Statistical significance was based on dual criteria of a ratio of change in gene expression >2 and a P < 0.01. Differential expression in 11 selected genes was further verified by real-time PCR. Functional pathways involved in retinal ageing were analyzed by an online software package (DAVID-2008) in differentially expressed gene lists. Age-related changes in differential expression in the identified retinal molecular pathways were further confirmed by immunohistochemical staining of retinal flat mounts and retinal cryosections.

RESULTS
With ageing of the retina, 298 genes were upregulated and 137 genes were downregulated. Functional annotation showed that genes linked to immune responses (Ir genes) and to tissue stress/injury responses (TS/I genes) were most likely to be modified by ageing. The Ir genes affected included those regulating leukocyte activation, chemotaxis, endocytosis, complement activation, phagocytosis, and myeloid cell differentiation, most of which were upregulated, with only a few downregulated. Increased microglial and complement activation in the aging retina was further confirmed by confocal microscopy of retinal tissues. The most strongly upregulated gene was the calcitonin receptor (Calcr; >40-fold in old versus young mice).

CONCLUSIONS
The results suggest that retinal ageing is accompanied by activation of gene sets, which are involved in local inflammatory responses. A modified form of low-grade chronic inflammation (para-inflammation) characterizes these aging changes and involves mainly the innate immune system. The marked upregulation of Calcr in ageing mice most likely reflects this chronic inflammatory/stress response, since calcitonin is a known systemic biomarker of inflammation/sepsis. © Association for Research in Vision and Ophthalmology.

Building Autonomous Sensitive Artificial Listeners

This paper describes a substantial effort to build a real-time interactive multimodal dialogue system with a focus on emotional and non-verbal interaction capabilities. The work is motivated by the aim to provide technology with competences in perceiving and producing the emotional and non-verbal behaviours required to sustain a conversational dialogue. We present the Sensitive Artificial Listener (SAL) scenario as a setting which seems particularly suited for the study of emotional and non- verbal behaviour, since it requires only very limited verbal understanding on the part of the machine. This scenario allows us to concentrate on non-verbal capabilities without having to address at the same time the challenges of spoken language understanding, task modeling etc. We first report on three prototype versions of the SAL scenario, in which the behaviour of the Sensitive Artificial Listener characters was determined by a human operator. These prototypes served the purpose of verifying the effectiveness of the SAL scenario and allowed us to collect data required for building system components for analysing and synthesising the respective behaviours. We then describe the fully autonomous integrated real-time system we created, which combines incremental analysis of user behaviour, dialogue management, and synthesis of speaker and listener behaviour of a SAL character displayed as a virtual agent. We discuss principles that should underlie the evaluation of SAL-type systems. Since the system is designed for modularity and reuse, and since it is publicly available, the SAL system has potential as a joint research tool in the affective computing research community.

ARE ARTIFICIAL NEURAL NETS AS SMART AS A RAT

The origins of artificial neural networks are related to animal conditioning theory: both are forms of connectionist theory, which in turn derives from the empiricist philosophers' principle of association. The parallel between animal learning and neural nets suggests that interaction between them should benefit both sides.

Communicating open systems

Just as conventional institutions are organisational structures for coordinating the activities of multiple interacting individuals, electronic institutions provide a computational analogue for coordinating the activities of multiple interacting software agents. In this paper, we argue that open multi-agent systems can be effectively designed and implemented as electronic institutions, for which we provide a comprehensive computational model. More specifically, the paper provides an operational semantics for electronic institutions, specifying the essential data structures, the state representation and the key operations necessary to implement them. We specify the agent workflow structure that is the core component of such electronic institutions and particular instantiations of knowledge representation languages that support the institutional model. In so doing, we provide the first formal account of the electronic institution concept in a rigorous and unambiguous way.

Targeting distributed systems in FastFlow

FastFlow is a structured parallel programming framework targeting shared memory multi-core architectures. In this paper we introduce a FastFlow extension aimed at supporting also a network of multi-core workstations. The extension supports the execution of FastFlow programs by coordinating-in a structured way-the fine grain parallel activities running on a single workstation. We discuss the design and the implementation of this extension presenting preliminary experimental results validating it on state-of-the-art networked multi-core nodes. © 2013 Springer-Verlag.

An efficient unbounded lock-free queue for multi-core systems

The use of efficient synchronization mechanisms is crucial for implementing fine grained parallel programs on modern shared cache multi-core architectures. In this paper we study this problem by considering Single-Producer/Single- Consumer (SPSC) coordination using unbounded queues. A novel unbounded SPSC algorithm capable of reducing the row synchronization latency and speeding up Producer-Consumer coordination is presented. The algorithm has been extensively tested on a shared-cache multi-core platform and a sketch proof of correctness is presented. The queues proposed have been used as basic building blocks to implement the FastFlow parallel framework, which has been demonstrated to offer very good performance for fine-grain parallel applications. © 2012 Springer-Verlag.

Lorentz TEM investigation of the switching behavior in artificial spin ice building blocks

Frustration – the inability to simultaneously satisfy all interactions – occurs in a wide range of systems including neural networks, water ice and magnetic systems. An example of the latter is the so called spin-ice in pyrochlore materials [1] which have attracted a lot of interest not least due to the emergence of magnetic monopole defects when the ‘ice rules’ governing the local ordering breaks down [2]. However it is not possible to directly measure the frustrated property – the direction of the magnetic moments – in such spin ice systems with current experimental techniques. This problem can be solved by instead studying artificial spin-ice systems where the molecular magnetic moments are replaced by nanoscale ferromagnetic islands [3-8]. Two different arrangements of the ferromagnetic islands have been shown to exhibit spin ice behaviour: a square lattice maintaining four moments at each vertex [3,8] and the Kagome lattice which has only three moments per vertex but equivalent interactions between them [4-7]. Magnetic monopole defects have been observed in both types of lattices [7-8]. One of the challenges when studying these artificial spin-ice systems is that it is difficult to arrive at the fully demagnetised ground-state [6-8].
Here we present a study of the switching behaviour of building blocks of the Kagome lattice influenced by the termination of the lattice. Ferromagnetic islands of nominal size 1000 nm by 100 nm were fabricated in five island blocks using electron-beam lithography and lift-off techniques of evaporated 18 nm Permalloy (Ni80Fe20) films. Each block consists of a central island with four arms terminated by a different number and placement of ‘injection pads’, see Figure 1. The islands are single domain and magnetised along their long axis. The structures were grown on a 50 nm thick electron transparent silicon nitride membrane to allow TEM observation, which was back-coated with a 5 nm film of Au to prevent charge build-up during the TEM experiments.
To study the switching behaviour the sample was subjected to a magnetic field strong enough to magnetise all the blocks in one direction, see Figure 1. Each block obeys the Kagome lattice ‘ice-rules’ of “2-in, 1-out” or “1-in, 2-out” in this fully magnetised state. Fresnel mode Lorentz TEM images of the sample were then recorded as a magnetic field of increasing magnitude was applied in the opposite direction. While the Fresnel mode is normally used to image magnetic domain structures [9] for these types of samples it is possible to deduce the direction of the magnetisation from the Lorentz contrast [5]. All images were recorded at the same over-focus judged to give good Lorentz contrast.
The magnetisation was found to switch at different magnitudes of the applied field for nominally identical blocks. However, trends could still be identified: all the blocks with any injection pads, regardless of placement and number, switched the direction of the magnetisation of their central island at significantly smaller magnitudes of the applied magnetic field than the blocks without injection pads. It can therefore be concluded that the addition of an injection pad lowers the energy barrier to switching the connected island, acting as a nucleation site for monopole defects. In these five island blocks the defects immediately propagate through to the other side, but in a larger lattice the monopoles could potentially become trapped at a vertex and observed [10].
References

[1] M J Harris et al, Phys Rev Lett 79 (1997) p.2554.
[2] C Castelnovo, R Moessner and S L Sondhi, Nature 451 (2008) p. 42.
[3] R F Wang et al, Nature 439 (2006) 303.
[4] M Tanaka et al, Phys Rev B 73 (2006) 052411.
[5] Y Qi, T Brintlinger and J Cumings, Phys Rev B 77 (2008) 094418.
[6] E Mengotti et al, Phys Rev B 78 (2008) 144402.
[7] S Ladak et al, Nature Phys 6 (2010) 359.
[8] C Phatak et al, Phys Rev B 83 (2011) 174431.
[9] J N Chapman, J Phys D 17 (1984) 623.
[10] The authors gratefully acknowledge funding from the EPSRC under grant number EP/D063329/1.

An extended framework for evidential reasoning systems

Based on the Dempster-Shafer (D-S) theory of evidence and G. Yen's (1989), extension of the theory, the authors propose approaches to representing heuristic knowledge by evidential mapping and pooling the mass distribution in a complex frame by partitioning that frame using Shafter's partition technique. The authors have generalized Yen's model from Bayesian probability theory to the D-S theory of evidence. Based on such a generalized model, an extended framework for evidential reasoning systems is briefly specified in which a semi-graph method is used to describe the heuristic knowledge. The advantage of such a method is that it can avoid the complexity of graphs without losing the explicitness of graphs. The extended framework can be widely used to build expert systems

Composition Games for Distributed Systems: the EU Grant games

We analyze ways by which people decompose into groups in distributed systems. We are interested in systems in which an agent can increase its utility by connecting to other agents, but must also pay a cost that increases with the size of the sys- tem. The right balance is achieved by the right size group of agents. We formulate and analyze three intuitive and realistic games and show how simple changes in the protocol can dras- tically improve the price of anarchy of these games. In partic- ular, we identify two important properties for a low price of anarchy: agreement in joining the system, and the possibil- ity of appealing a rejection from a system. We show that the latter property is especially important if there are some pre- existing constraints regarding who may collaborate (or com- municate) with whom.

Managing adaptivity in parallel systems

The management of non-functional features (performance, security, power management, etc.) is traditionally a difficult, error prone task for programmers of parallel applications. To take care of these non-functional features, autonomic managers running policies represented as rules using sensors and actuators to monitor and transform a running parallel application may be used. We discuss an approach aimed at providing formal tool support to the integration of independently developed autonomic managers taking care of different non-functional concerns within the same parallel application. Our approach builds on the Behavioural Skeleton experience (autonomic management of non-functional features in structured parallel applications) and on previous results on conflict detection and resolution in rule-based systems. © 2013 Springer-Verlag Berlin Heidelberg.

Tools for Finding Inconsistencies in Real-world Logic-based Systems

Currently there is extensive theoretical work on inconsistencies in logic-based systems. Recently, algorithms for identifying inconsistent clauses in a single conjunctive formula have demonstrated that practical application of this work is possible. However, these algorithms have not been extended for full knowledge base systems and have not been applied to real-world knowledge. To address these issues, we propose a new algorithm for finding the inconsistencies in a knowledge base using existing algorithms for finding inconsistent clauses in a formula. An implementation of this algorithm is then presented as an automated tool for finding inconsistencies in a knowledge base and measuring the inconsistency of formulae. Finally, we look at a case study of a network security rule set for exploit detection (QRadar) and suggest how these automated tools can be applied.