Detection of advanced persistent threat using machine-learning correlation analysis

As one of the most serious types of cyber attack, Advanced Persistent Threats (APT) have caused major concerns on a global scale. APT refers to a persistent, multi-stage attack with the intention to compromise the system and gain information from the targeted system, which has the potential to cause significant damage and substantial financial loss. The accurate detection and prediction of APT is an ongoing challenge. This work proposes a novel machine learning-based system entitled MLAPT, which can accurately and rapidly detect and predict APT attacks in a systematic way. The MLAPT runs through three main phases: (1) Threat detection, in which eight methods have been developed to detect different techniques used during the various APT steps. The implementation and validation of these methods with real traffic is a significant contribution to the current body of research; (2) Alert correlation, in which a correlation framework is designed to link the outputs of the detection methods, aims to identify alerts that could be related and belong to a single APT scenario; and (3) Attack prediction, in which a machine learning-based prediction module is proposed based on the correlation framework output, to be used by the network security team to determine the probability of the early alerts to develop a complete APT attack. MLAPT is experimentally evaluated and the presented sy

Endocytosis contributes to BMP2-induced Smad signalling and neuronal growth

Bone morphogenetic protein 2 (BMP2) is a neurotrophic factor which induces the growth of midbrain dopaminergic (DA) neurons in vitro and in vivo, and its neurotrophic effects have been shown to be dependent on activation of BMP receptors (BMPRs) and Smad 1/5/8 signalling. However, the precise intracellular cascades that regulate BMP2-BMPR-Smad-signalling-induced neurite growth remain unknown. Endocytosis has been shown to regulate Smad 1/5/8 signalling and differentiation induced by BMPs. However, these studies were carried out in non-neural cells. Indeed, there are scant reports regarding the role of endocytosis in BMP-Smad signalling in neurons. To address this, and to further characterise the mechanisms regulating the neurotrophic effects of BMP2, the present study examined the role of dynamin-dependent endocytosis in BMP2-induced Smad signalling and neurite growth in the SH-SY5Y neuronal cell line. The activation, temporal kinetics and magnitude of Smad 1/5/8 signalling induced by BMP2 were significantly attenuated by dynasore-mediated inhibition of endocytosis in SH-SY5Y cells. Furthermore, BMP2-induced increases in neurite length and neurite branching in SH-SY5Y cells were significantly reduced following inhibition of dynamin-dependent endocytosis using dynasore. This study demonstrates that BMP2-induced Smad signalling and neurite growth is regulated by dynamin-dependent endocytosis in a model of human midbrain dopaminergic neurons

Inhibition of miR-181a promotes midbrain neuronal growth through a Smad1/5-dependent mechanism: implications for Parkinson’s disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease, and is characterized by the progressive degeneration of nigrostriatal dopaminergic (DA) neurons. Current PD treatments are symptomatic, wear off over time and do not protect against DA neuronal loss. Finding a way to re-grow midbrain DA (mDA) neurons is a promising disease-modifying therapeutic strategy for PD. However, reliable biomarkers are required to allow such growth-promoting approaches to be applied early in the disease progression. miR-181a has been shown to be dysregulated in PD patients, and has been identified as a potential biomarker for PD. Despite studies demonstrating the enrichment of miR-181a in the brain, specifically in neurites of postmitotic neurons, the role of miR-181a in mDA neurons remains unknown. Herein, we used cell culture models of human mDA neurons to investigate a potential role for miR-181a in mDA neurons. We used a bioninformatics analysis to identify that miR-181a targets components of the bone morphogenetic protein (BMP) signalling pathway, including the transcription factors Smad1 and Smad5, which we find are expressed by rat mDA neurons and are required for BMP-induced neurite growth. We also found that inhibition of neuronal miR-181a, resulted in increased Smad signalling, and induced neurite growth in SH-SY5Y cells. Finally, using embryonic rat cultures, we demonstrated that miR-181a inhibition induces ventral midbrain (VM) and cortical neuronal growth. These data describe a new role for miR-181a in mDA neurons, and provide proof of principle that miR-181a dysresgulation in PD may alter the activation state of signalling pathways important for neuronal growth in neurons affected in PD

Targeting bone morphogenetic protein signalling in midbrain dopaminergic neurons as a therapeutic approach in Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by the degeneration of midbrain dopaminergic (mDA) neurons and their axons, and aggregation of α-synuclein, which leads to motor and late-stage cognitive impairments. As the motor symptoms of PD are caused by the degeneration of a specific population of mDA neurons, PD lends itself to neurotrophic factor therapy. The goal of this therapy is to apply a neurotrophic factor that can slow down, halt or even reverse the progressive degeneration of mDA neurons. While the best known neurotrophic factors are members of the glial cell line-derived neurotrophic factor (GDNF) family, their lack of clinical efficacy to date means that it is important to continue to study other neurotrophic factors. Bone morphogenetic proteins (BMPs) are naturally secreted proteins that play critical roles during nervous system development and in the adult brain. In this review, we provide an overview of the BMP ligands, BMP receptors (BMPRs) and their intracellular signalling effectors, the Smad proteins. We review the available evidence that BMP–Smad signalling pathways play an endogenous role in mDA neuronal survival in vivo, before outlining how exogenous application of BMPs exerts potent effects on mDA neuron survival and axon growth in vitro and in vivo. We discuss the molecular mechanisms that mediate these effects, before highlighting the potential of targeting the downstream effectors of BMP–Smad signalling as a novel neuroprotective approach to slow or stop the degeneration of mDA neurons in PD

Characterisation of the role of canonical BMP-Smad 1/5/8 signalling in the development of ventral midbrain dopaminergic neurons

Ventral midbrain (VM) dopaminergic (DA) neurons, which project to the dorsal striatum via the nigrostriatal pathway, are progressively degenerated in Parkinson’s disease (PD). The identification of the instructive factors that regulate midbrain DA neuron development, and the subsequent elucidation of the molecular bases of their effects, is vital. Such an understanding would facilitate the generation of transplantable DA neurons from stem cells and the identification of developmentally-relevant neurotrophic factors, the two most promising therapeutic approaches for PD. Two related members of the bone morphogenetic protein (BMP) family, BMP2 and growth/differentiation factor (GDF) 5, which signal via a canonical Smad 1/5/8 signalling pathway, have been shown to have neurotrophic effects on midbrain DA neurons both in vitro and in vivo, and may function to regulate VM DA neuronal development. However, the molecular (signalling pathway(s)) and cellular (direct neuronal or indirect via glial cells) mechanisms of their effects remain to be elucidated. The present thesis hypothesised that canonical Smad signalling mediates the direct effects of BMP2 and GDF5 on the development of VM DA neurons. By activating, modulating and/or inhibiting various components of the BMP-Smad signalling pathway, this research demonstrated that GDF5- and BMP2-induced neurite outgrowth from midbrain DA neurons is dependent on BMP type I receptor activation of the Smad signalling pathway. The role of glial cell-line derived neurotrophic factor (GDNF)-signalling, dynamin-dependent endocytosis and Smad interacting protein-1 (Sip1) regulation, in the neurotrophic effects of BMP2 and GDF5 were determined. Finally, the in vitro development of VM neural stem cells (NSCs) was characterised, and the ability of GDF5 and BMP2 to induce these VM NSCs towards DA neuronal differentiation was investigated. Taken together, these experiments identify GDF5 and BMP2 as novel regulators of midbrain DA neuronal induction and differentiation, and demonstrate that their effects on DA neurons are mediated by canonical BMPR-Smad signalling

A dataflow IR for memory efficient RIPL compilation to FPGAs

Field programmable gate arrays (FPGAs) are fundamentally different to fixed processors architectures because their memory hierarchies can be tailored to the needs of an algorithm. FPGA compilers for high level languages are not hindered by fixed memory hierarchies. The constraint when compiling to FPGAs is the availability of resources. In this paper we describe how the dataflow intermediary of our declarative FPGA image processing DSL called RIPL (Rathlin Image Processing Language) enables us to constrain memory. We use five benchmarks to demonstrate that memory use with RIPL is comparable to the Vivado HLS OpenCV library without the need for language pragmas to guide hardware synthesis. The benchmarks also show that RIPL is more expressive than the Darkroom FPGA image processing language

Flight tests of IFR landing approach systems for helicopters

Joint NASA/FAA helicopter flight tests were conducted to investigate airborne radar approaches (ARA) and microwave landing system (MLS) approaches. Flight-test results were utilized to prove NASA with a data base to be used as a performance measure for advanced guidance and navigation concepts, and to provide FAA with data for establishment of TERPS criteria. The first flight-test investigation consisted of helicopter IFR approaches to offshore oil rigs in the Gulf of Mexico, using weather/mapping radar, operational pilots, and a Bell 212 helicopter. The second flight-test investigation consisted of IFR MLS approaches at Crows Landing (near Ames Research Center), with a Bell UH-1H helicopter, using NASA, FAA, and operational industry pilots. Tests are described and results discussed

Effects of intracerebral neurotrophic factor application on motor symptoms in Parkinson's disease: a systematic review and meta-analysis

Introduction: Neurotrophic factors (NTFs) have been evaluated for neuroprotective effects in Parkinson's disease (PD). However, clinical trials examining the efficacy of intracerebral administration of NTFs on motor symptoms in PD have produced mixed results, and are thus inconclusive. The objective of this systematic review and meta-analysis was to determine the effects of intracerebral NTF application on motor symptoms in people with PD. Methods: We searched PubMed, MEDLINE, EMBASE, and Cochrane from inception through to March 31 2016 for open-label trials and randomized controlled trials (RCTs) which intracerebrally administered NTFs to PD patients, and which performed motor examination of Unified Parkinson's Disease Rating Scale. Results: Eight studies with a total of 223 participants were included. Fixed effects analysis revealed that NTF treatment did not significantly reduce motor symptoms in PD patients compared to placebo controls (P = 0.98). Combining open-label and RCT data, both treatment with NTFs (P < 0.001) and treatment with placebo (P < 0.05) significantly improved motor function in PD patients when compared to predicted symptoms in untreated PD controls. Finally, random effects analysis revealed that NTF-treated PD patients were not significantly likely to improve following intracerebral NTF administration (P = 0.25). Conclusion: In conclusion, intracerebral NTF administration does not improve motor symptoms in PD patients, when compared to placebo-treated controls. These findings may guide therapeutic decisions and inform future research on NTFs and their application in PD

A small molecule activator of p300/CBP histone acetyltransferase promotes survival and neurite growth in a cellular model of Parkinson’s disease

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterised by motor and non-motor symptoms, resulting from the degeneration of nigrostriatal dopaminergic neurons and peripheral autonomic neurons. Given the limited success of neurotrophic factors in clinical trials, there is a need to identify new small molecule drugs and drug targets to develop novel therapeutic strategies to protect all neurons that degenerate in PD. Epigenetic dysregulation has been implicated in neurodegenerative disorders, while targeting histone acetylation is a promising therapeutic avenue for PD. We and others have demonstrated that histone deacetylase inhibitors have neurotrophic effects in experimental models of PD. Activators of histone acetyltransferases (HAT) provide an alternative approach for the selective activation of gene expression, however little is known about the potential of HAT activators as drug therapies for PD. To explore this potential, the present study investigated the neurotrophic effects of CTPB (N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide), which is a potent small molecule activator of the histone acetyltransferase p300/CBP, in the SH-SY5Y neuronal cell line. We report that CTPB promoted the survival and neurite growth of the SH-SY5Y cells, and also protected these cells from cell death induced by the neurotoxin 6-hydroxydopamine. This study is the first to investigate the phenotypic effects of the HAT activator CTPB, and to demonstrate that p300/CBP HAT activation has neurotrophic effects in a cellular model of PD

Relaxation oscillations suppression and undamping in a hybrid photonic crystal laser

As demand towards cloud-based services and high-performance computations grows, it imposes requirements on data center performance, and efficiency. Taking advantage of the mature CMOS process technology, and the fact that silicon is the basic material of electronics industry, silicon photonics makes possible production photonic integrated circuits that satisfy these requirements. Here we explore the short-cavity hybrid laser consisting of a III-V amplifier integrated with a silicon photonic crystal (PhC) cavity reflector by so-called butt-coupling approach. The laser possesses great stability characteristics meeting the criteria for data center interconnect applications. The PhC reflector having a Q-factor of 104 at the lasing wavelength 1535 nm can be considered as a narrow-bandwidth filter. The laser demonstrates single mode and eventless operation without any dynamics on the background, and smooth radiofrequency spectrum without evidence of relaxation oscillation frequency. The latter fact is beneficial for many applications, and indicates extremely high damping in PhC laser, where the photon cavity lifetime is greatly improved by the high-Q PhC cavity reflector. We confirm our experimental observations by theory based on delay differential equation model for a single-section semiconductor laser. We reveal the effective damping of the laser, when the detuning between the filter peak and the laser cavity mode is small, and the imaginary parts of the model eigenvalues equal zero. It is possible to undamp the relaxation oscillations forcing self-Q-switched operation in the laser owing to the cumulative action of the alpha-factor and the narrow filter. In conclusion, we experimentally and theoretically demonstrated that relaxation oscillations can be suppressed in the short-cavity semiconductor laser with a narrow intracavity frequency filter. Additionally, on the basis of our analysis we expect the undamping of relaxation oscillations, and self-pulsations when the cavity mode is detuned from the filter peak frequency. The results might be useful for applications in data communications.Publisher PD