Molecular network analysis using reverse phase protein microarrays for patient tailored therapy.

The practice of medicine has always aimed at individualized treatment of disease. The relationship between patient and physician has always been a personal one, and the physician's choice of treatment has been intended to be the best fit for the patient's needs. The necessary pooling/grouping of disease families and their assignment to a number of drugs or treatment methods has, consequently, led to an increase in the number of effective therapies. However, given the heterogeneity of most human diseases, and cancer specifically, it is currently impossible for the treating clinician to effectively predict a patient's response and outcome based on current technologies, much less the idiosyncratic resistances and adverse effects associated with the limited therapeutic options.

Wind speed measurements of land-falling tropical cyclones using SWIRLnet, a portable anemometer network

Wind speed measurement systems are sparse in the tropical regions of Australia. Given this, tropical cyclone wind speeds impacting communities are seldom measured and often only ‘guestimated’ by analysing the extent of damage to structures. In an attempt to overcome this dearth of data, a re-locatable network of anemometers to be deployed prior to tropical cyclone landfall is currently being developed. This paper discusses design criteria of the network’s tripods and tie down system, proposed deployment of the anemometers, instrumentation and data logging. Preliminary assessment of the anemometer response indicates a reliable system for measuring the spectral component of wind with frequencies of approximately 1 Hz. This system limitation highlights an important difference between the capabilities of modern instrumentation and that of the Dines anemometer (around 0.2 seconds) that was used to develop much of the design criteria within the Australian building code and wind loading standard.

Cholesterol regulates Syntaxin 6 trafficking at trans-Golgi network endosomal boundaries.

Inhibition of cholesterol export from late endosomes causes cellular cholesterol imbalance, including cholesterol depletion in the trans-Golgi network (TGN). Here, using Chinese hamster ovary (CHO) Niemann-Pick type C1 (NPC1) mutant cell lines and human NPC1 mutant fibroblasts, we show that altered cholesterol levels at the TGN/endosome boundaries trigger Syntaxin 6 (Stx6) accumulation into VAMP3, transferrin, and Rab11-positive recycling endosomes (REs). This increases Stx6/VAMP3 interaction and interferes with the recycling of αVβ3 and α5β1 integrins and cell migration, possibly in a Stx6-dependent manner. In NPC1 mutant cells, restoration of cholesterol levels in the TGN, but not inhibition of VAMP3, restores the steady-state localization of Stx6 in the TGN. Furthermore, elevation of RE cholesterol is associated with increased amounts of Stx6 in RE. Hence, the fine-tuning of cholesterol levels at the TGN-RE boundaries together with a subset of cholesterol-sensitive SNARE proteins may play a regulatory role in cell migration and invasion.

Use of reverse phase protein microarrays and reference standard development for molecular network analysis of metastatic ovarian carcinoma

Cancer can be defined as a deregulation or hyperactivity in the ongoing network of intracellular and extracellular signaling events. Reverse phase protein microarray technology may offer a new opportunity to measure and profile these signaling pathways, providing data on post-translational phosphorylation events not obtainable by gene microarray analysis. Treatment of ovarian epithelial carcinoma almost always takes place in a metastatic setting since unfortunately the disease is often not detected until later stages. Thus, in addition to elucidation of the molecular network within a tumor specimen, critical questions are to what extent do signaling changes occur upon metastasis and are there common pathway elements that arise in the metastatic microenvironment. For individualized combinatorial therapy, ideal therapeutic selection based on proteomic mapping of phosphorylation end points may require evaluation of the patient's metastatic tissue. Extending these findings to the bedside will require the development of optimized protocols and reference standards. We have developed a reference standard based on a mixture of phosphorylated peptides to begin to address this challenge.

Cortical organization of environmental sounds by attribute

Semantic knowledge is supported by a widely distributed neuronal network, with differential patterns of activation depending upon experimental stimulus or task demands. Despite a wide body of knowledge on semantic object processing from the visual modality, the response of this semantic network to environmental sounds remains relatively unknown. Here, we used fMRI to investigate how access to different conceptual attributes from environmental sound input modulates this semantic network. Using a range of living and manmade sounds, we scanned participants whilst they carried out an object attribute verification task. Specifically, we tested visual perceptual, encyclopedic, and categorical attributes about living and manmade objects relative to a high-level auditory perceptual baseline to investigate the differential patterns of response to these contrasting types of object-related attributes, whilst keeping stimulus input constant across conditions. Within the bilateral distributed network engaged for processing environmental sounds across all conditions, we report here a highly significant dissociation within the left hemisphere between the processing of visual perceptual and encyclopedic attributes of objects.

Buffer scheme with battery energy storage capability for enhancement of network transient stability and load ride-through

This paper examines a buffer scheme to mitigate the negative impacts of power-conditioned loads on network voltage and transient stabilities. The scheme is based on the use of battery energy-storage systems in the buffers. The storage systems ensure that protected loads downstream of the buffers can ride through upstream voltage sags and swells. Also, by controlling the buffers to operate in either constant impedance or constant power modes, power is absorbed or injected by the storage systems. The scheme thereby regulates the rotor-angle deviations of generators and enhances network transient stability. A computational method is described in which the capacity of the storage systems is determined to achieve simultaneously the above dual objectives of load ride-through and stability enhancement. The efficacy of the resulting scheme is demonstrated through numerical examples.

Network-targeted combination therapy : a new concept in cancer treatment

Toxicity is a major concern for anti-neoplastic drugs, with much of the existing pharmacopoeia being characterized by a very narrow therapeutic index. 'Network-targeted' combination therapy is a promising new concept in cancer therapy, whereby therapeutic index might be improved by targeting multiple nodes in a cell's signaling network, rather than a single node. Here, we examine the potential of this novel approach, illustrating how therapeutic benefit could be achieved with smaller doses of the necessary agents.

What I want for my Social Network privacy

Social Networks (SN) users have various privacy requirements to protect their information; to address this issue, a six-stage thematic analysis of scholarly articles related to SN user privacy concerns were synthesized. Then this research combines mixed methods research employing the strengths of quantitative and qualitative research to investigate general SN users, and thus construct a new set of ?ve primary and Twenty-?ve secondary SN user privacy requirements. Such an approach has been rarely used to examine the privacy requirements. Factor analysis results show superior agreement with theoretical predictions and signi?cant improvement over previous alternative models of SN user privacy requirements. This research presented here has the potential to provide for the development of more sophisticated privacy controls which will increase the ability of SN users to: specify their rights in SNs and to determine the protection of their own SN data.

Angiogenesis in old-aged subjects after ischemic stroke : a cautionary note for investigators

Angiogenesis represents a form of neovascularisation of exceptional importance in numerous pathological conditions including stroke. In this context it is directly related to neuroregeneration which is seen in close proximity. However, numerous experimental data have been drawn from studies that have ignored the age criterion. This is extremely important as angiogenesis is different in young versus old subjects. Extrapolating data obtained from studies performed in young subjects or "in vitro" to old-age patients could lead to inexact conclusions since the dynamics of angiogenesis is age-dependent.The current review covers the key features of brain senescence including morphological and functional changes related to the brain parenchyma, its vascular network and blood flow which could possibly influence the process of angiogenesis. This is followed by a description of post-stroke angiogenesis and its relationship to neuroregeneration and its modulation by vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF 1), the most important factors active in old brain after ischemic injury.

A gray-box neural network-based model identification and fault estimation scheme for nonlinear dynamic systems

A novel gray-box neural network model (GBNNM), including multi-layer perception (MLP) neural network (NN) and integrators, is proposed for a model identification and fault estimation (MIFE) scheme. With the GBNNM, both the nonlinearity and dynamics of a class of nonlinear dynamic systems can be approximated. Unlike previous NN-based model identification methods, the GBNNM directly inherits system dynamics and separately models system nonlinearities. This model corresponds well with the object system and is easy to build. The GBNNM is embedded online as a normal model reference to obtain the quantitative residual between the object system output and the GBNNM output. This residual can accurately indicate the fault offset value, so it is suitable for differing fault severities. To further estimate the fault parameters (FPs), an improved extended state observer (ESO) using the same NNs (IESONN) from the GBNNM is proposed to avoid requiring the knowledge of ESO nonlinearity. Then, the proposed MIFE scheme is applied for reaction wheels (RW) in a satellite attitude control system (SACS). The scheme using the GBNNM is compared with other NNs in the same fault scenario, and several partial loss of effect (LOE) faults with different severities are considered to validate the effectiveness of the FP estimation and its superiority.

Confucius Institutes and the network communication approach to public diplomacy

Discussions of public diplomacy in recent years have paid a growing amount of attention to networks. This network perspective is understood to provide insights into various issues of public diplomacy, such as its effects, credibility, reputation, identity and narratives. This paper applies the network idea to analyse China’s Confucius Institutes initiative. It understands Confucius Institutes as a global network and argues that this network structure has potential implications for the operation of public and cultural diplomacy that are perhaps underestimated in existing accounts of Chinese cultural diplomacy. In particular, it is noted that the specific setup of Confucius Institutes requires the engagement of local stakeholders, in a way that is less centralised and more networked than comparable cultural diplomacy institutions. At the same time, the development of a more networked for of public cultural diplomacy is challenged in practice by both practical issues and the configuration of China’s state-centric public diplomacy system informed by the political constitution of the Chinese state.

The brain-specific microRNA miR-128b regulates the formation of fear-extinction memory

MicroRNAs are small non-coding RNAs that mediate post-transcriptional gene silencing. Fear-extinction learning in C57/Bl6J mice led to increased expression of the brain-specific microRNA miR-128b, which disrupted stability of several plasticity-related target genes and regulated formation of fear-extinction memory. Increased miR-128b activity may therefore facilitate the transition from retrieval of the original fear memory toward the formation of a new fear-extinction memory.

Promoting law student well-being through the curriculum

The Australian tertiary sector is becoming increasingly concerned about the psychological well-being of its students.Empirical research in Australia indicates that more than one-third of law students suffer from psychological distress, and the competitive, isolated, adversarial learning environment at law school has been suggested as partly responsible (Brain and Mind Research Institute, 2009). This fellowship program has mobilised strategic change to improve the psychological health of law students. It has lead and stimulated advancement in the legal curriculum, its pedagogy, and assessment practice to better engage, motivate and support student learning of law, focussing on the potential of non-adversarial legal practice. A new conceptual framework for legal education has been developed, demonstrating the pursuit of excellence in the teaching of law, and raising the profile of learning and teaching in Australian law schools. In addition the fellowship has created a national community of practice around this issue through the Wellness Network for Law, and made significant contributions to research and scholarship in the field.

Exploring the properties of macroscopic fundamental diagram : analysing Brisbane urban network

This thesis explored traffic characteristics at the aggregate level for area-wide traffic monitoring of large urban area. It focused on three aspects: understanding a macroscopic network performance under real-time traffic information provision, measuring traffic performance of a signalised arterial network using available data sets, and discussing network zoning for monitoring purposes in the case of Brisbane, Australia. This work presented the use of probe vehicle data for estimating traffic state variables, and illustrated dynamic features of regional traffic performance of Brisbane. The results confirmed the viability and effectiveness of area-wide traffic monitoring.