A human-simulated immune evolutionary computation approach

Premature convergence to local optimal solutions is one of the main difficulties when using evolutionary algorithms in real-world optimization problems. To prevent premature convergence and degeneration phenomenon, this paper proposes a new optimization computation approach, human-simulated immune evolutionary algorithm (HSIEA). Considering that the premature convergence problem is due to the lack of diversity in the population, the HSIEA employs the clonal selection principle of artificial immune system theory to preserve the diversity of solutions for the search process. Mathematical descriptions and procedures of the HSIEA are given, and four new evolutionary operators are formulated which are clone, variation, recombination, and selection. Two benchmark optimization functions are investigated to demonstrate the effectiveness of the proposed HSIEA.

Decentralized detector generation in cooperative intrusion detection system

We consider Cooperative Intrusion Detection System (CIDS) which is a distributed AIS-based (Artificial Immune System) IDS where nodes collaborate over a peer-to-peer overlay network. The AIS uses the negative selection algorithm for the selection of detectors (e.g., vectors of features such as CPU utilization, memory usage and network activity). For better detection performance, selection of all possible detectors for a node is desirable but it may not be feasible due to storage and computational overheads. Limiting the number of detectors on the other hand comes with the danger of missing attacks. We present a scheme for the controlled and decentralized division of detector sets where each IDS is assigned to a region of the feature space. We investigate the trade-off between scalability and robustness of detector sets. We address the problem of self-organization in CIDS so that each node generates a distinct set of the detectors to maximize the coverage of the feature space while pairs of nodes exchange their detector sets to provide a controlled level of redundancy. Our contribution is twofold. First, we use Symmetric Balanced Incomplete Block Design, Generalized Quadrangles and Ramanujan Expander Graph based deterministic techniques from combinatorial design theory and graph theory to decide how many and which detectors are exchanged between which pair of IDS nodes. Second, we use a classical epidemic model (SIR model) to show how properties from deterministic techniques can help us to reduce the attack spread rate.

Innate and adaptive immunity at mucosal surfaces of the female reproductive tract : stratification and integration of immune protection against the transmission of sexually transmitted infections

This review examines the multiple levels of pre-existing immunity in the upper and lower female reproductive tract. In addition, we highlight the need for further research of innate and adaptive immune protection of mucosal surfaces in the female reproductive tract. Innate mechanisms include the mucus lining, a tight epithelial barrier and the secretion of antimicrobial peptides and cytokines by epithelial and innate immune cells. Stimulation of the innate immune system also serves to bridge the adaptive arm resulting in the generation of pathogen-specific humoral and cell-mediated immunity. Less understood are the multiple components that act in a coordinated way to provide a network of ongoing protection. Innate and adaptive immunity in the human female reproductive tract are influenced by the stage of menstrual cycle and are directly regulated by the sex steroid hormones, progesterone and estradiol. Furthermore, the effect of hormones on immunity is mediated both directly on immune and epithelial cells and indirectly by stimulating growth factor secretion from stromal cells. The goal of this review is to focus on the diverse aspects of the innate and adaptive immune systems that contribute to a unique network of protection throughout the female reproductive tract.

The ghrelin receptor isoforms (GHS-R1a and GHS-R1b) and GPR39 : an investigation into receptor dimerisation

Prostate cancer is the second most common cause of cancer-related deaths in Western males. Current diagnostic, prognostic and treatment approaches are not ideal and advanced metastatic prostate cancer is incurable. There is an urgent need for improved adjunctive therapies and markers for this disease. GPCRs are likely to play a significant role in the initiation and progression of prostate cancer. Over the last decade, it has emerged that G protein coupled receptors (GPCRs) are likely to function as homodimers and heterodimers. Heterodimerisation between GPCRs can result in the formation of novel pharmacological receptors with altered functional outcomes, and a number of GPCR heterodimers have been implicated in the pathogenesis of human disease. Importantly, novel GPCR heterodimers represent potential new targets for the development of more specific therapeutic drugs. Ghrelin is a 28 amino acid peptide hormone which has a unique n-octanoic acid post-translational modification. Ghrelin has a number of important physiological roles, including roles in appetite regulation and the stimulation of growth hormone release. The ghrelin receptor is the growth hormone secretagogue receptor type 1a, GHS-R1a, a seven transmembrane domain GPCR, and GHS-R1b is a C-terminally truncated isoform of the ghrelin receptor, consisting of five transmembrane domains. Growing evidence suggests that ghrelin and the ghrelin receptor isoforms, GHS-R1a and GHS-R1b, may have a role in the progression of a number of cancers, including prostate cancer. Previous studies by our research group have shown that the truncated ghrelin receptor isoform, GHS-R1b, is not expressed in normal prostate, however, it is expressed in prostate cancer. The altered expression of this truncated isoform may reflect a difference between a normal and cancerous state. A number of mutant GPCRs have been shown to regulate the function of their corresponding wild-type receptors. Therefore, we investigated the potential role of interactions between GHS-R1a and GHS-R1b, which are co-expressed in prostate cancer and aimed to investigate the function of this potentially new pharmacological receptor. In 2005, obestatin, a 23 amino acid C-terminally amidated peptide derived from preproghrelin was identified and was described as opposing the stimulating effects of ghrelin on appetite and food intake. GPR39, an orphan GPCR which is closely related to the ghrelin receptor, was identified as the endogenous receptor for obestatin. Recently, however, the ability of obestatin to oppose the effects of ghrelin on appetite and food intake has been questioned, and furthermore, it appears that GPR39 may in fact not be the obestatin receptor. The role of GPR39 in the prostate is of interest, however, as it is a zinc receptor. Zinc has a unique role in the biology of the prostate, where it is normally accumulated at high levels, and zinc accumulation is altered in the development of prostate malignancy. Ghrelin and zinc have important roles in prostate cancer and dimerisation of their receptors may have novel roles in malignant prostate cells. The aim of the current study, therefore, was to demonstrate the formation of GHS-R1a/GHS-R1b and GHS-R1a/GPR39 heterodimers and to investigate potential functions of these heterodimers in prostate cancer cell lines. To demonstrate dimerisation we first employed a classical co-immunoprecipitation technique. Using cells co-overexpressing FLAG- and Myc- tagged GHS-R1a, GHS-R1b and GPR39, we were able to co-immunoprecipitate these receptors. Significantly, however, the receptors formed high molecular weight aggregates. A number of questions have been raised over the propensity of GPCRs to aggregate during co-immunoprecipitation as a result of their hydrophobic nature and this may be misinterpreted as receptor dimerisation. As we observed significant receptor aggregation in this study, we used additional methods to confirm the specificity of these putative GPCR interactions. We used two different resonance energy transfer (RET) methods; bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET), to investigate interactions between the ghrelin receptor isoforms and GPR39. RET is the transfer of energy from a donor fluorophore to an acceptor fluorophore when they are in close proximity, and RET methods are, therefore, applicable to the observation of specific protein-protein interactions. Extensive studies using the second generation bioluminescence resonance energy transfer (BRET2) technology were performed, however, a number of technical limitations were observed. The substrate used during BRET2 studies, coelenterazine 400a, has a low quantum yield and rapid signal decay. This study highlighted the requirement for the expression of donor and acceptor tagged receptors at high levels so that a BRET ratio can be determined. After performing a number of BRET2 experimental controls, our BRET2 data did not fit the predicted results for a specific interaction between these receptors. The interactions that we observed may in fact represent ‘bystander BRET’ resulting from high levels of expression, forcing the donor and acceptor into close proximity. Our FRET studies employed two different FRET techniques, acceptor photobleaching FRET and sensitised emission FRET measured by flow cytometry. We were unable to observe any significant FRET, or FRET values that were likely to result from specific receptor dimerisation between GHS-R1a, GHS-R1b and GPR39. While we were unable to conclusively demonstrate direct dimerisation between GHS-R1a, GHS-R1b and GPR39 using several methods, our findings do not exclude the possibility that these receptors interact. We aimed to investigate if co-expression of combinations of these receptors had functional effects in prostate cancers cells. It has previously been demonstrated that ghrelin stimulates cell proliferation in prostate cancer cell lines, through ERK1/2 activation, and GPR39 can stimulate ERK1/2 signalling in response to zinc treatments. Additionally, both GHS-R1a and GPR39 display a high level of constitutive signalling and these constitutively active receptors can attenuate apoptosis when overexpressed individually in some cell types. We, therefore, investigated ERK1/2 and AKT signalling and cell survival in prostate cancer the potential modulation of these functions by dimerisation between GHS-R1a, GHS-R1b and GPR39. Expression of these receptors in the PC-3 prostate cancer cell line, either alone or in combination, did not alter constitutive ERK1/2 or AKT signalling, basal apoptosis or tunicamycin-stimulated apoptosis, compared to controls. In summary, the potential interactions between the ghrelin receptor isoforms, GHS-R1a and GHS-R1b, and the related zinc receptor, GPR39, and the potential for functional outcomes in prostate cancer were investigated using a number of independent methods. We did not definitively demonstrate the formation of these dimers using a number of state of the art methods to directly demonstrate receptor-receptor interactions. We investigated a number of potential functions of GPR39 and GHS-R1a in the prostate and did not observe altered function in response to co-expression of these receptors. The technical questions raised by this study highlight the requirement for the application of extensive controls when using current methods for the demonstration of GPCR dimerisation. Similar findings in this field reflect the current controversy surrounding the investigation of GPCR dimerisation. Although GHS-R1a/GHS-R1b or GHS-R1a/GPR39 heterodimerisation was not clearly demonstrated, this study provides a basis for future investigations of these receptors in prostate cancer. Additionally, the results presented in this study and growing evidence in the literature highlight the requirement for an extensive understanding of the experimental method and the performance of a range of controls to avoid the spurious interpretation of data gained from artificial expression systems. The future development of more robust techniques for investigating GPCR dimerisation is clearly required and will enable us to elucidate whether GHS-R1a, GHS-R1b and GPR39 form physiologically relevant dimers.

Patterns

In recent years there has been widespread interest in patterns, perhaps provoked by a realisation that they constitute a fundamental brain activity and underpin many artificial intelligence systems. Theorised concepts of spatial patterns including scale, proportion, and symmetry, as well as social and psychological understandings are being revived through digital/parametric means of visualisation and production. The effect of pattern as an ornamental device has also changed from applied styling to mediated dynamic effect. The interior has also seen patterned motifs applied to wall coverings, linen, furniture and artefacts with the effect of enhancing aesthetic appreciation, or in some cases causing psychological and/or perceptual distress (Rodemann 1999). ----- ----- While much of this work concerns a repeating array of surface treatment, Philip Ball’s The Self- Made Tapestry: Pattern Formation in Nature (1999) suggests a number of ways that patterns are present at the macro and micro level, both in their formation and disposition. Unlike the conventional notion of a pattern being the regular repetition of a motif (geometrical or pictorial) he suggests that in nature they are not necessarily restricted to a repeating array of identical units, but also include those that are similar rather than identical (Ball 1999, 9). From his observations Ball argues that they need not necessarily all be the same size, but do share similar features that we recognise as typical. Examples include self-organized patterns on a grand scale such as sand dunes, or fractal networks caused by rivers on hills and mountains, through to patterns of flow observed in both scientific experiments and the drawings of Leonardo da Vinci.

Ghrelin and cancer

Ghrelin is a peptide hormone that was originally isolated from the stomach as the endogenous ligand for the growth hormone secretagogue receptor (GHSR). Ghrelin has many functions, including the regulation of appetite and gut motility, growth hormone release from the anterior pituitary and roles in the cardiovascular and immune systems. Ghrelin and its receptor are expressed in a number of cancers and cancer cell lines and may play a role in processes associated with cancer progression, including cell proliferation, apoptosis, and cell invasion and migration.

Solving inherent problems of anomaly detection by cooperation

Anomaly detection compensates shortcomings of signature-based detection such as protecting against Zero-Day exploits. However, Anomaly Detection can be resource-intensive and is plagued by a high false-positive rate. In this work, we address these problems by presenting a Cooperative Intrusion Detection approach for the AIS, the Artificial Immune System, as an example for an anomaly detection approach. In particular we show, how the cooperative approach reduces the false-positive rate of the detection and how the overall detection process can be organized to account for the resource constraints of the participating devices. Evaluations are carried out with the novel network simulation environment NeSSi as well as formally with an extension to the epidemic spread model SIR

Small RNA viruses of insects : expression in plants and RNA silencing

Interest in insect small RNA viruses (SRVs) has grown slowly but steadily. A number of new viruses have been analyzed at the sequence level, adding to our knowledge of their diversity at the level of both individual virus species and families. In particular, a number of possible new virus families have emerged. This research has largely been driven by interest in their potential for pest control, as well as in their importance as the causal agents of disease in beneficial arthropods. At the same time, research into known viruses has made valuable contributions to our understanding of an emerging new field of central importance to molecular biology-the existence of RNA-based gene silencing, developmental control, and adaptive immune systems in eukaryotes. Subject to RNA-based adaptive immune responses in their hosts, viruses have evolved a variety of genes encoding proteins capable of suppressing the immune response. Such genes were first identified in plant viruses, but the first examples known from animal viruses were identified in insect RNA viruses. This chapter will address the diversity of insect SRVs, and attempts to harness their simplicity in the engineering of transgenic plants expressing viruses for resistance to insect pests. We also describe RNA interference and antiviral pathways identified in plants and animals, how they have led viruses to evolve genes capable of suppressing such adaptive immunity, and the problems presented by these pathways for the strategy of expressing viruses in transgenic plants. Approaches for countering these problems are also discussed. © 2006 Elsevier Inc. All rights reserved.

Interrelations between acute and chronic exercise and the immune and endocrine systems

Interaction between the endocrine and immune system is necessary to regulate our health. However, under some conditions, stress hormones can overstimulate or suppress the immune system, resulting in harmful consequences (1). Stress is often considered negative, yet it is an intrinsic part of everyday life. Stress is not clearly defined; it is context-specific and depends on the nature of factors that challenge our body. Internal stimuli will elicit different stress reactions compared with external stimuli (1). Similarly, some stressors will induce responses that may benefit survival, whereas others will cause disturbances that may endanger our health. Stress also depends on how our bodies perceive and respond to stressful stimuli (1).

Design of physiological control and magnetic levitation systems for a total artificial heart

Total Artificial Hearts are mechanical pumps which can be used to replace the failing natural heart. This novel study developed a means of controlling a new design of pump to reproduce physiological flow bringing closer the realisation of a practical artificial heart. Using a mathematical model of the device, an optimisation algorithm was used to determine the best configuration for the magnetic levitation system of the pump. The prototype device was constructed and tested in a mock circulation loop. A physiological controller was designed to replicate the Frank-Starling like balancing behaviour of the natural heart. The device and controller provided sufficient support for a human patient while also demonstrating good response to various physiological conditions and events. This novel work brings the design of a practical artificial heart closer to realisation.

Visualization of complex biological systems: An immune response model using OpenGL

In this paper we present an update on our novel visualization technologies based on cellular immune interaction from both large-scale spatial and temporal perspectives. We do so with a primary motive: to present a visually and behaviourally realistic environment to the community of experimental biologists and physicians such that their knowledge and expertise may be more readily integrated into the model creation and calibration process. Visualization aids understanding as we rely on visual perception to make crucial decisions. For example, with our initial model, we can visualize the dynamics of an idealized lymphatic compartment, with antigen presenting cells (APC) and cytotoxic T lymphocyte (CTL) cells. The visualization technology presented here offers the researcher the ability to start, pause, zoom-in, zoom-out and navigate in 3-dimensions through an idealised lymphatic compartment.