Dendritic Cells for SYN Scan Detection

Artificial immune systems have previously been applied to the problem of intrusion detection. The aim of this research is to develop an intrusion detection system based on the function of Dendritic Cells (DCs). DCs are antigen presenting cells and key to the activation of the human immune system, behaviour which has been abstracted to form the Dendritic Cell Algorithm (DCA). In algorithmic terms, individual DCs perform multi-sensor data fusion, asynchronously correlating the fused data signals with a secondary data stream. Aggregate output of a population of cells is analysed and forms the basis of an anomaly detection system. In this paper the DCA is applied to the detection of outgoing port scans using TCP SYN packets. Results show that detection can be achieved with the DCA, yet some false positives can be encountered when simultaneously scanning and using other network services. Suggestions are made for using adaptive signals to alleviate this uncovered problem

Information Fusion for Anomaly Detection with the Dendritic Cell Algorithm

Dendritic cells are antigen presenting cells that provide a vital link between the innate and adaptive immune system, providing the initial detection of pathogenic invaders. Research into this family of cells has revealed that they perform information fusion which directs immune responses. We have derived a Dendritic Cell Algorithm based on the functionality of these cells, by modelling the biological signals and differentiation pathways to build a control mechanism for an artificial immune system. We present algorithmic details in addition to experimental results, when the algorithm was applied to anomaly detection for the detection of port scans. The results show the Dendritic Cell Algorithm is sucessful at detecting port scans.Comment: 21 pages, 17 figures, Information Fusio

Continuous volumetric imaging via an optical phase-locked ultrasound lens

In vivo imaging at high spatiotemporal resolution is key to the understanding of complex biological systems. We integrated an optical phase-locked ultrasound lens into a two-photon fluorescence microscope and achieved microsecond-scale axial scanning, thus enabling volumetric imaging at tens of hertz. We applied this system to multicolor volumetric imaging of processes sensitive to motion artifacts, including calcium dynamics in behaving mouse brain and transient morphology changes and trafficking of immune cells

Image informatics strategies for deciphering neuronal network connectivity

Brain function relies on an intricate network of highly dynamic neuronal connections that rewires dramatically under the impulse of various external cues and pathological conditions. Among the neuronal structures that show morphologi- cal plasticity are neurites, synapses, dendritic spines and even nuclei. This structural remodelling is directly connected with functional changes such as intercellular com- munication and the associated calcium-bursting behaviour. In vitro cultured neu- ronal networks are valuable models for studying these morpho-functional changes. Owing to the automation and standardisation of both image acquisition and image analysis, it has become possible to extract statistically relevant readout from such networks. Here, we focus on the current state-of-the-art in image informatics that enables quantitative microscopic interrogation of neuronal networks. We describe the major correlates of neuronal connectivity and present workflows for analysing them. Finally, we provide an outlook on the challenges that remain to be addressed, and discuss how imaging algorithms can be extended beyond in vitro imaging studies

Proteomic analyses reveal misregulation of LIN28 expression and delayed timing of glial differentiation in human iPS cells with MECP2 loss-of-function.

Rett syndrome (RTT) is a pervasive developmental disorder caused by mutations in MECP2. Complete loss of MECP2 function in males causes congenital encephalopathy, neurodevelopmental arrest, and early lethality. Induced pluripotent stem cell (iPSC) lines from male patients harboring mutations in MECP2, along with control lines from their unaffected fathers, give us an opportunity to identify some of the earliest cellular and molecular changes associated with MECP2 loss-of-function (LOF). We differentiated iPSC-derived neural progenitor cells (NPCs) using retinoic acid (RA) and found that astrocyte differentiation is perturbed in iPSC lines derived from two different patients. Using highly stringent quantitative proteomic analyses, we found that LIN28, a gene important for cell fate regulation and developmental timing, is upregulated in mutant NPCs compared to WT controls. Overexpression of LIN28 protein in control NPCs suppressed astrocyte differentiation and reduced neuronal synapse density, whereas downregulation of LIN28 expression in mutant NPCs partially rescued this synaptic deficiency. These results indicate that the pathophysiology of RTT may be caused in part by misregulation of developmental timing in neural progenitors, and the subsequent consequences of this disruption on neuronal and glial differentiation

Complementary Sensory and Associative Microcircuitry in Primary Olfactory Cortex

The three-layered primary olfactory (piriform) cortex is the largest component of the olfactory cortex. Sensory and intracortical inputs converge on principal cells in the anterior piriform cortex (aPC).Wecharacterize organization principles of the sensory and intracortical microcircuitry of layer II and III principal cells in acute slices of rat aPC using laser-scanning photostimulation and fast two-photon population Ca²⁺ imaging. Layer II and III principal cells are set up on a superficial-to-deep vertical axis. We found that the position on this axis correlates with input resistance and bursting behavior. These parameters scale with distinct patterns of incorporation into sensory and associative microcircuits, resulting in a converse gradient of sensory and intracortical inputs. In layer II, sensory circuits dominate superficial cells, whereas incorporation in intracortical circuits increases with depth. Layer III pyramidal cells receive more intracortical inputs than layer II pyramidal cells, but with an asymmetric dorsal offset. This microcircuit organization results in a diverse hybrid feedforward/recurrent network of neurons integrating varying ratios of intracortical and sensory input depending on a cell’s position on the superficial-to-deep vertical axis. Since burstiness of spiking correlates with both the cell’s location on this axis and its incorporation in intracortical microcircuitry, the neuronal output mode may encode a given cell’s involvement in sensory versus associative processing

Dendrodendritic synaptic signals in olfactory bulb granule cells: local spine boost and global low-threshold spike

In the mammalian olfactory bulb, axonless granule cells process synaptic input and output reciprocally within large spines. The nature of the calcium signals that underlie the presynaptic and postsynaptic function of these spines is mostly unknown. Using two-photon imaging in acute rat brain slices and glomerular stimulation of mitral/tufted cells, we observed two forms of action potential-independent synaptic Ca2+ signals in granule cell dendrites. Weak activation of mitral/tufted cells produced stochastic Ca2+ transients in individual granule cell spines. These transients were strictly localized to the spine head, indicating a local passive boosting or spine spike. Ca2+ sources for these local synaptic events included NMDA receptors, voltage-dependent calcium channels, and Ca2+-induced Ca2+ release from internal stores. Stronger activation of mitral/tufted cells produced a low-threshold Ca2+ spike (LTS) throughout the granule cell apical dendrite. This global spike was mediated by T-type Ca2+ channels and represents a candidate mechanism for subthreshold lateral inhibition in the olfactory bulb. The coincidence of local input and LTS in the spine resulted in summation of local and global Ca2+ signals, a dendritic computation that could endow granule cells with subthreshold associative plasticity

Nanoscale-targeted patch-clamp recordings of functional presynaptic ion channels

Important modulatory roles have been attributed to presynaptic NMDA receptors (NMDARs) located on cerebellar interneuron terminals. Evidence supporting a presynaptic location includes an increase in the frequency of mini events following the application of NMDA and gold particle-labelled NMDA receptor antibody localisation. However, more recent work, using calcium indicators, casts doubt on the idea of presynaptic NMDARs because basket cell varicosities did not show the expected calcium rise following either the local iontophoresis of L-aspartate or the two-photon uncaging of glutamate. (In theory such calcium imaging is sensitive enough to detect the calcium rise from even a single activated receptor.) It has therefore been suggested that the effects of NMDA are mediated via the activation of somatodendritic channels, which subsequently cause a subthreshold depolarization of the axon. Here we report results from a vibrodissociated preparation of cerebellar Purkinje cells, in which the interneuron cell bodies are no longer connected but many of their terminal varicosities remain attached and functional. This preparation can retain both inhibitory and excitatory inputs. We find that the application of NMDA increases the frequency of both types of synaptic event. The characteristics of these events suggest they can originate from interneuron, parallel fiber and even climbing fiber terminals. Interestingly, retrograde signalling seems to activate only the inhibitory terminals. Finally, antibody staining of these cells shows NMDAR-like immunoreactivity co-localised with synaptic markers. Since the Purkinje cells show no evidence of postsynaptic NMDAR-mediated currents, we conclude that functional NMDA receptors are located on presynaptic terminals

Integrating real-time analysis with the dendritic cell algorithm through segmentation

As an immune inspired algorithm, the Dendritic Cell Algorithm (DCA) has been applied to a range of problems, particularly in the area of intrusion detection. Ideally, the intrusion detection should be performed in real-time, to continuously detect misuses as soon as they occur. Consequently, the analysis process performed by an intrusion detection system must operate in real-time or near-to real-time. The analysis process of the DCA is currently performed offline, therefore to improve the algorithm's performance we suggest the development of a real-time analysis component. The initial step of the development is to apply segmentation to the DCA. This involves segmenting the current output of the DCA into slices and performing the analysis in various ways. Two segmentation approaches are introduced and tested in this paper, namely antigen based segmentation (ABS) and time based segmentation (TBS). The results of the corresponding experiments suggest that applying segmentation produces different and significantly better results in some cases, when compared to the standard DCA without segmentation. Therefore, we conclude that the segmentation is applicable to the DCA for the purpose of real-time analysis