Integrating Innate and Adaptive Immunity for Intrusion Detection

Network Intrusion Detection Systems (NIDS) monitor a net- work with the aim of discerning malicious from benign activity on that network. While a wide range of approaches have met varying levels of success, most IDS’s rely on having access to a database of known attack signatures which are written by security experts. Nowadays, in order to solve problems with false positive alerts, correlation algorithms are used to add additional structure to sequences of IDS alerts. However, such techniques are of no help in discovering novel attacks or variations of known attacks, something the human immune system (HIS) is capable of doing in its own specialised domain. This paper presents a novel immune algorithm for application to an intrusion detection problem. The goal is to discover packets containing novel variations of attacks covered by an existing signature base.

Experimenting with Innate Immunity

libtissue is a software system for implementing and testing AIS algorithms on real-world computer security problems. AIS algorithms are implemented as a collection of cells, antigen and signals interacting within a tissue compartment. Input data to the tissue comes in the form of realtime events generated by sensors monitoring a system under surveillance, and cells are actively able to affect the monitored system through response mechanisms. libtissue is being used by researchers on a project at the University of Nottingham to explore the application of a range of immune-inspired algorithms to problems in intrusion detection. This talk describes the architecture and design of libtissue, along with the implementation of a simple algorithm and its application to a computer security problem.

Libtissue - Implementing Innate Immunity

In a previous paper the authors argued the case for incorporating ideas from innate immunity into artificial immune systems (AISs) and presented an outline for a conceptualframework for such systems. A number of key general properties observed in the biological innate and adaptive immune systems were highlighted, and how such properties might be instantiated in artificial systems was discussed in detail. The next logical step is to take these ideas and build a software system with which AISs with these properties can be implemented and experimentally evaluated. This paper reports on the results of that step - the libtissue system.

'Towards a Conceptual Framework for Innate Immunity'

Innate immunity now occupies a central role in immunology. However, artificial immune system models have largely been inspired by adaptive not innate immunity. This paper reviews the biological principles and properties of innate immunity and, adopting a conceptual framework, asks how these can be incorporated into artificial models. The aim is to outline a meta-framework for models of innate immunity.

Novel strategies for targeting innate immune responses to influenza.

NlmCategory="UNASSIGNED">We previously reported that TLR4(-/-) mice are refractory to mouse-adapted A/PR/8/34 (PR8) influenza-induced lethality and that therapeutic administration of the TLR4 antagonist Eritoran blocked PR8-induced lethality and acute lung injury (ALI) when given starting 2 days post infection. Herein we extend these findings: anti-TLR4- or -TLR2-specific IgG therapy also conferred significant protection of wild-type (WT) mice from lethal PR8 infection. If treatment is initiated 3 h before PR8 infection and continued daily for 4 days, Eritoran failed to protect WT and TLR4(-/-) mice, implying that Eritoran must block a virus-induced, non-TLR4 signal that is required for protection. Mechanistically, we determined that (i) Eritoran blocks high-mobility group B1 (HMGB1)-mediated, TLR4-dependent signaling in vitro and circulating HMGB1 in vivo, and an HMGB1 inhibitor protects against PR8; (ii) Eritoran inhibits pulmonary lung edema associated with ALI; (iii) interleukin (IL)-1β contributes significantly to PR8-induced lethality, as evidenced by partial protection by IL-1 receptor antagonist (IL-1Ra) therapy. Synergistic protection against PR8-induced lethality was achieved when Eritoran and the antiviral drug oseltamivir were administered starting 4 days post infection. Eritoran treatment does not prevent development of an adaptive immune response to subsequent PR8 challenge. Overall, our data support the potential of a host-targeted therapeutic approach to influenza infection.Mucosal Immunology advance online publication 27 January 2016; doi:10.1038/mi.2015.141.

Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes

Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. From the Clinical Editor: Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting.

Hemolytic activity of alternative complement pathway as an indicator of innate immunity in pacu (Piaractus mesopotamicus)

The objective of this study was to evaluate the methodology to establish the hemolytic activity of alternative complement pathway as an indicator of the innate immunity in Brazilian fish pacu (Piaractus mesopotamicus), in addition to verifying the influence of β-glucan as an immunostimulant. Fish were fed with diets containing 0, 0.1 and 1% β-glucan, during seven days, and then inoculated with Aeromonas hydrophila. Seven days after the challenge, they were bled for serum extraction. The methodology consisted of a kinetic assay that allows calculating the required time for serum proteins of the complement to promote 50% lysis of a rabbit red blood cell suspension. The method developed in mammals was successfully applied for pacu and determined that the hemolytic activity of the proteins of the complement system (alternative pathway) increased after the pathogen challenge, but was not influenced by the β-glucan treatment.

Impact of exercise on innate immunity in multiple sclerosis progression and symptomatology

Multiple Sclerosis (MS), an idiopathic progressive immune-mediated neurological disorder of the central nervous system (CNS), is characterized by recurrent episodes of inflammatory demyelination and consequent axonal deterioration. It accounts for functional deterioration and lasting disability among young adults. A body of literature demonstrates that physical activity counteracts fatigue and depression and may improve overall quality of life in MS patients. Furthermore, much data indicates that exercise ameliorates chronic neuroinflammation and its related pathologies by tipping cytokine profiles toward an anti-inflammatory signature. Recent data has focused on the direct impact of exercise training on the innate immune system by targeting toll-like receptors (TLRs), signaling pattern recognition receptors that govern the innate immune response, shedding light on the physiological role of TLRs in health and disease. Indeed, TLRs continue to emerge as players in the neuroinflammatory processes underpinning MS. This review will highlight evidence that physical activity and exercise are potential immunomodulatory therapies, targeting innate signaling mechanism(s) to modulate MS symptom development and progression.

Issues in the development of pitch labelling skill

Pitch discrimination skills are important for general musicianship. The ability to name musical notes or produce orally any named note without the benefit of a known reference is called Absolute Pitch (AP) and is comparatively rare. Relative Pitch (RP) is the ability to name notes when a known reference is available. AP has historically been regarded as being innate. This paper will examine the notion that pitch discrimination skill is based on knowledge constructed through a suite of experiences. That is, it is learnt. In particular, it will be argued that early experiences promote the development of AP. Second it will argue that AP and RP represent different types of knowledge, and that this knowledge emerges from different experiences. AP is a unique research phenomenon because it spans the fields of cognition and perception, in that it links verbal labels with physiological sensations, and because of its rarity. It may provide a vantage for investigating the nature/nurture of musicianship; expertise; knowledge structure development; and the role of knowledge in perception. The study of AP may inform educational practice and curriculum design both in music and cross-curriculur. This paper will report an initial investigation into the similarities and differences between the musical experiences of AP possessors and the manifestation of their AP skill. Interview and questionnaire data will be used for the development and proposal of a preliminary model for AP development.

Diversity of accuracy profiles for absolute pitch recognition

Most advanced musicians are able to identify and label a heard pitch if given an opportunity to compare it to a known reference note. This is called ‘relative pitch’ (RP). A much rarer skill is the ability to identify and label a heard pitch without the need for a reference. This is colloquially referred to as ‘perfect pitch’, but appears in the academic literature as ‘absolute pitch’ (AP). AP is considered by many as a remarkable skill. As people do not seem able to develop it intentionally, it is generally regarded as innate. It is often seen as a unitary skill and that a set of identifiable criteria can distinguish those who possess the skill from those who do not. However, few studies have interrogated these notions. The present study developed and applied an interactive computer program to map pitch-labelling responses to various tonal stimuli without a known reference tone available to participants. This approach enabled the identification of the elements of sound that impacted on AP. Pitch-labelling responses of 14 participants with AP were recorded for their accuracy. Each participant’s response to the stimuli was unique. Their accuracy of labelling varied across dimensions such as timbre, range and tonality. The diversity of performance between individuals appeared to reflect their personal musical experience histories.

Chlamydial infection and spatial ascension of the female genital tract : a novel hybrid cellular automata and continuum mathematical model

Sexually transmitted chlamydial infection initially establishes in the endocervix in females, but if the infection ascends the genital tract, significant disease, including infertility, can result. Many of the mechanisms associated with chlamydial infection kinetics and disease ascension are unknown. We attempt to elucidate some of these processes by developing a novel mathematical model, using a cellular automata–partial differential equation model. We matched our model outputs to experimental data of chlamydial infection of the guinea-pig cervix and carried out sensitivity analyses to determine the relative influence of model parameters. We found that the rate of recruitment and action of innate immune cells to clear extracellular chlamydial particles and the rate of passive movement of chlamydial particles are the dominant factors in determining the early course of infection, magnitude of the peak chlamydial time course and the time of the peak. The rate of passive movement was found to be the most important factor in determining whether infection would ascend to the upper genital tract. This study highlights the importance of early innate immunity in the control of chlamydial infection and the significance of motility-diffusive properties and the adaptive immune response in the magnitude of infection and in its ascension.

The NOURISH randomised control trial : positive feeding practices and food preferences in early childhood - a primary prevention program for childhood obesity

Background Primary prevention of childhood overweight is an international priority. In Australia 20-25% of 2-8 year olds are already overweight. These children are at substantially increased the risk of becoming overweight adults, with attendant increased risk of morbidity and mortality. Early feeding practices determine infant exposure to food (type, amount, frequency) and include responses (eg coercion) to infant feeding behaviour (eg. food refusal). There is correlational evidence linking parenting style and early feeding practices to child eating behaviour and weight status. A focus on early feeding is consistent with the national focus on early childhood as the foundation for life-long health and well being. The NOURISH trial aims to implement and evaluate a community-based intervention to promote early feeding practices that will foster healthy food preferences and intake and preserve the innate capacity to self-regulate food intake in young children. Methods/Design This randomised controlled trial (RCT) aims to recruit 820 first-time mothers and their healthy term infants. A consecutive sample of eligible mothers will be approached postnatally at major maternity hospitals in Brisbane and Adelaide. Initial consent will be for re-contact for full enrolment when the infants are 4-7 months old. Individual mother- infant dyads will be randomised to usual care or the intervention. The intervention will provide anticipatory guidance via two modules of six fortnightly parent education and peer support group sessions, each followed by six months of regular maintenance contact. The modules will commence when the infants are aged 4-7 and 13-16 months to coincide with establishment of solid feeding, and autonomy and independence, respectively. Outcome measures will be assessed at baseline, with follow up at nine and 18 months. These will include infant intake (type and amount of foods), food preferences, feeding behaviour and growth and self-reported maternal feeding practices and parenting practices and efficacy. Covariates will include sociodemographics, infant feeding mode and temperament, maternal weight status and weight concern and child care exposure. Discussion Despite the strong rationale to focus on parents’ early feeding practices as a key determinant of child food preferences, intake and self-regulatory capacity, prospective longitudinal and intervention studies are rare. This trial will be amongst to provide Level II evidence regarding the impact of an intervention (commencing prior to age 12 months) on children’s eating patterns and behaviours. Trial Registration: ACTRN12608000056392

Dancing with nature : rhythm and harmony in extreme sport participation

Research on extreme sports has downplayed the importance of the athletes' connection to the natural world. This neglect stems, in part, from the assumption that these activities derive their meaning primarily from risk. The authors' long-term research reveals that the interplay between adventure athletes and the natural world is, in fact, crucial for many participants. This study used hermeneutic and phenomenological analysis of first-hand accounts of these sports and interviews with 15 veteran participants. These included BASE jumpers, big-wave surfers, extreme skiers, waterfall kayakers, extreme mountaineers and solo rope-free climbers. Participants spoke extensively about developing a deep relationship with the natural world akin to an intimate 'dance' between actively engaged partners. Our experience-based analysis has found that extreme sports aficionados do not simply view the natural world as a commodity, a stage for risk taking, or vehicle for self-gratification. On the contrary, for veteran adventure athletes the natural world acts as a facilitator to a deeper, more positive understanding of self and its place in the environment. For some, nature was described as omnipresent and ubiquitous, and a source of innate power and personal meaning. The authors explore how these findings may augment the delivery of more 'ecocentric' programmes in the outdoor adventure field.

A critical analysis of sperm donation practices : the personal and social effects of disrupting the unity of biological and social relatedness for the offspring

This thesis critically analyses sperm donation practices from a child-centred perspective. It examines the effects, both personal and social, of disrupting the unity of biological and social relatedness in families affected by donor conception. It examines how disruption is facilitated by a process of mediation which is detailed using a model provided by Sunderland (2002). This model identifies mediating movements - alienation, translation, re-contextualisation and absorption - which help to explain the powerful and dominating material, and social and political processes which occur in biotechnology, or in reproductive technology in this case. The understanding of such movements and mediation of meanings is inspired by the complementary work of Silverstone (1999) and Sunderland. This model allows for a more critical appreciation of the movement of meaning from previously inalienable aspects of life to alienable products through biotechnology (Sunderland, 2002). Once this mediation in donor conception is subjected to critical examination here, it is then approached from different angles of investigation. The thesis posits that two conflicting notions of the self are being applied to fertility-frustrated adults and the offspring of reproductive interventions. Adults using reproductive interventions receive support to maximise their genetic continuity, but in so doing they create and dismiss the corresponding genetic discontinuity produced for the offspring. The offspring’s kinship and identity are then framed through an experimental postmodernist notion, presenting them as social rather than innate constructs. The adults using the reproductive intervention, on the other hand, have their identity and kinship continuity framed and supported as normative, innate, and based on genetic connection. This use of shifting frameworks is presented as unjust and harmful, creating double standards and a corrosion of kinship values, connection and intelligibility between generations; indeed, it is put forward as adult-centric. The analysis of other forms of human kinship dislocation provided by this thesis explores an under-utilised resource which is used to counter the commonly held opinion that any disruption of social and genetic relatedness for donor offspring is insignificant. The experiences of adoption and the stolen generations are used to inform understanding of the personal and social effects of such kinship disruption and potential reunion for donor offspring. These examples, along with laws governing international human rights, further strengthen the appeal here for normative principles and protections based on collective knowledge and standards to be applied to children of reproductive technology. The thesis presents the argument that the framing and regulation of reproductive technology is excessively influenced by industry providers and users. The interests of these parties collide with and corrode any accurate assessments and protections afforded to the children of reproductive technology. The thesis seeks to counter such encroachments and concludes by presenting these protections, frameworks, and human experiences as resources which can help to address the problems created for the offspring of such reproductive interventions, thereby illustrating why these reproductive interventions should be discontinued.

The nonconceptual gateway to early word learning

My research investigates why nouns are learned disproportionately more frequently than other kinds of words during early language acquisition (Gentner, 1982; Gleitman, et al., 2004). This question must be considered in the context of cognitive development in general. Infants have two major streams of environmental information to make meaningful: perceptual and linguistic. Perceptual information flows in from the senses and is processed into symbolic representations by the primitive language of thought (Fodor, 1975). These symbolic representations are then linked to linguistic input to enable language comprehension and ultimately production. Yet, how exactly does perceptual information become conceptualized? Although this question is difficult, there has been progress. One way that children might have an easier job is if they have structures that simplify the data. Thus, if particular sorts of perceptual information could be separated from the mass of input, then it would be easier for children to refer to those specific things when learning words (Spelke, 1990; Pylyshyn, 2003). It would be easier still, if linguistic input was segmented in predictable ways (Gentner, 1982; Gleitman, et al., 2004) Unfortunately the frequency of patterns in lexical or grammatical input cannot explain the cross-cultural and cross-linguistic tendency to favor nouns over verbs and predicates. There are three examples of this failure: 1) a wide variety of nouns are uttered less frequently than a smaller number of verbs and yet are learnt far more easily (Gentner, 1982); 2) word order and morphological transparency offer no insight when you contrast the sentence structures and word inflections of different languages (Slobin, 1973) and 3) particular language teaching behaviors (e.g. pointing at objects and repeating names for them) have little impact on children's tendency to prefer concrete nouns in their first fifty words (Newport, et al., 1977). Although the linguistic solution appears problematic, there has been increasing evidence that the early visual system does indeed segment perceptual information in specific ways before the conscious mind begins to intervene (Pylyshyn, 2003). I argue that nouns are easier to learn because their referents directly connect with innate features of the perceptual faculty. This hypothesis stems from work done on visual indexes by Zenon Pylyshyn (2001, 2003). Pylyshyn argues that the early visual system (the architecture of the "vision module") segments perceptual data into pre-conceptual proto-objects called FINSTs. FINSTs typically correspond to physical things such as Spelke objects (Spelke, 1990). Hence, before conceptualization, visual objects are picked out by the perceptual system demonstratively, like a finger pointing indicating ‘this’ or ‘that’. I suggest that this primitive system of demonstration elaborates on Gareth Evan's (1982) theory of nonconceptual content. Nouns are learnt first because their referents attract demonstrative visual indexes. This theory also explains why infants less often name stationary objects such as plate or table, but do name things that attract the focal attention of the early visual system, i.e., small objects that move, such as ‘dog’ or ‘ball’. This view leaves open the question how blind children learn words for visible objects and why children learn category nouns (e.g. 'dog'), rather than proper nouns (e.g. 'Fido') or higher taxonomic distinctions (e.g. 'animal').