Mathematical modeling of the cancer cell’s control circuitry : paving the way to individualized therapeutic strategies

Cancer is a disease of signal transduction in which the dysregulation of the network of intracellular and extracellular signaling cascades is sufficient to thwart the cells finely-tuned biochemical control mechanisms. A keen interest in the mathematical modeling of cell signaling networks and the regulation of signal transduction has emerged in recent years, and has produced a glimmer of insight into the sophisticated feedback control and network regulation operating within cells. In this review, we present an overview of published theoretical studies on the control aspects of signal transduction, emphasizing the role and importance of mechanisms such as ‘ultrasensitivity’ and feedback loops. We emphasize that these exquisite and often subtle control strategies represent the key to orchestrating ‘simple’ signaling behaviors within the complex intracellular network, while regulating the trade-off between sensitivity and robustness to internal and external perturbations. Through a consideration of these apparent paradoxes, we explore how the basic homeostasis of the intracellular signaling network, in the face of carcinogenesis, can lead to neoplastic progression rather than cell death. A simple mathematical model is presented, furnishing a vivid illustration of how ‘control-oriented’ models of the deranged signaling networks in cancer cells may enucleate improved treatment strategies, including patient-tailored combination therapies, with the potential for reduced toxicity and more robust and potent antitumor activity.

Degradation modeling and monitoring of machines using operation-specific hidden Markov models

In this paper, a novel data-driven approach to monitoring of systems operating under variable operating conditions is described. The method is based on characterizing the degradation process via a set of operation-specific hidden Markov models (HMMs), whose hidden states represent the unobservable degradation states of the monitored system while its observable symbols represent the sensor readings. Using the HMM framework, modeling, identification and monitoring methods are detailed that allow one to identify a HMM of degradation for each operation from mixed-operation data and perform operation-specific monitoring of the system. Using a large data set provided by a major manufacturer, the new methods are applied to a semiconductor manufacturing process running multiple operations in a production environment.

Keyword field-free conjunctive keyword searches on encrypted data and extension for dynamic groups

We consider the following problem: a user stores encrypted documents on an untrusted server, and wishes to retrieve all documents containing some keywords without any loss of data confidentiality. Conjunctive keyword searches on encrypted data have been studied by numerous researchers over the past few years, and all existing schemes use keyword fields as compulsory information. This however is impractical for many applications. In this paper, we propose a scheme of keyword field-free conjunctive keyword searches on encrypted data, which affirmatively answers an open problem asked by Golle et al. at ACNS 2004. Furthermore, the proposed scheme is extended to the dynamic group setting. Security analysis of our constructions is given in the paper.

Modeling of protein signaling networks in clinical proteomics

Molecular interactions that underlie pathophysiological states are being elucidated using techniques that profile proteomicend points in cellular systems. Within the field of cancer research, protein interaction networks play pivotal roles in the establishment and maintenance of the hallmarks of malignancy, including cell division, invasion, and migration. Multiple complementary tools enable a multifaceted view of how signal protein pathway alterations contribute to pathophysiological states.One pivotal technique is signal pathway profiling of patient tissue specimens. This microanalysis technology provides a proteomic snapshot at one point in time of cells directly procured from the native context of a tumor micro environment. To study the adaptive patterns of signal pathway events over time, before and after experimental therapy, it is necessary to obtain biopsies from patients before, during, and after therapy. A complementary approach is the profiling of cultured cell lines with and without treatment. Cultured cell models provide the opportunity to study short-term signal changes occurring over minutes to hours. Through this type of system, the effects of particular pharmacological agents may be used to test the effects of signal pathway inhibition or activation on multiple endpoints within a pathway. The complexity of the data generated has necessitated the development of mathematical models for optimal interpretation of interrelated signaling pathways. In combination,clinical proteomic biopsy profiling, tissue culture proteomic profiling, and mathematical modeling synergistically enable a deeper understanding of how protein associations lead to disease states and present new insights into the design of therapeutic regimens.

Towards a multiple-goal pursuit and multilevel view of continuing information technology usage : a process model integration and a research agenda

The value of information technology (IT) is often realized when continuously being used after users’ initial acceptance. However, previous research on continuing IT usage is limited for dismissing the importance of mental goals in directing users’ behaviors and for inadequately accommodating the group context of users. This in-progress paper offers a synthesis of several literature to conceptualize continuing IT usage as multilevel constructs and to view IT usage behavior as directed and energized by a set of mental goals. Drawing from the self-regulation theory in the social psychology, this paper proposes a process model, positioning continuing IT usage as multiple-goal pursuit. An agent-based modeling approach is suggested to further explore causal and analytical implications of the proposed process model.

Lower partial moment and information entropy-based dynamic electricity purchasing strategy

In the electricity market environment, load-serving entities (LSEs) will inevitably face risks in purchasing electricity because there are a plethora of uncertainties involved. To maximize profits and minimize risks, LSEs need to develop an optimal strategy to reasonably allocate the purchased electricity amount in different electricity markets such as the spot market, bilateral contract market, and options market. Because risks originate from uncertainties, an approach is presented to address the risk evaluation problem by the combined use of the lower partial moment and information entropy (LPME). The lower partial moment is used to measure the amount and probability of the loss, whereas the information entropy is used to represent the uncertainty of the loss. Electricity purchasing is a repeated procedure; therefore, the model presented represents a dynamic strategy. Under the chance-constrained programming framework, the developed optimization model minimizes the risk of the electricity purchasing portfolio in different markets because the actual profit of the LSE concerned is not less than the specified target under a required confidence level. Then, the particle swarm optimization (PSO) algorithm is employed to solve the optimization model. Finally, a sample example is used to illustrate the basic features of the developed model and method.

Detection of dynamic primary user with cooperative spectrum sensing

In this paper we demonstrate that existing cooperative spectrum sensing formulated for static primary users cannot accurately detect dynamic primary users regardless of the information fusion method. Performance error occurs as the sensing parameters calculated by the conventional detector result in sensing performance that violates the sensing requirements. Furthermore, the error is accumulated and compounded by the number of cooperating nodes. To address this limitation, we design and implement the duty cycle detection model for the context of cooperative spectrum sensing to accurately calculate the sensing parameters that satisfy the sensing requirements. We show that longer sensing duration is required to compensate for dynamic primary user traffic.

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.

An integrated modeling and risk analysis tool for mine water interactions

Poor mine water management can lead to corporate, environmental and social risks. These risks become more pronounced as mining operations move into areas of water scarcity and/or increase climatic variability while also managing increased demand, lower ore grades and increased strip ratios. Therefore, it is vital that mine sites better understand these risks in order to implement management practices to address them. Systems models provide an effective approach to understand complex networks, particularly across multiple scales. Previous work has represented mine water interactions using systems model on a mine site scale. Here, we expand on that work by present an integrated tool that uses a systems modeling approach to represent mine water interactions on a site and regional scale and then analyses the risks associated with events stemming from those interactions. A case study is presented to represent three indicative corporate, environmental and social risks associated with a mine site that exists in a water scarce region. The tool is generic and flexible, and can be used in many scenarios to provide significant potential utility to the mining industry.

Digital Modeling, Integrated Project Delivery and Industry Transformation: An Australian Case Study

This research is focused on realizing productivity benefits for the delivery of transport infrastructure in the Australian construction industry through the use of building information modeling (BIM), virtual design and construction (VDC) and integrated project delivery (IPD). Specific objectives include: (I) building an understanding of the institutional environment, business systems and support mechanisms (e.g., training and skilling) which impact on the uptake of BIM/VDC; (II) gathering data to undertake a cross-country analysis of these environments; and (III) providing strategic and practical outcomes to guide the uptake of such processes in Australia. Activities which will inform this research include a review of academic literature and industry documentation, semi-formal interviews in Australia and Sweden, and a cross-country comparative analysis to determine factors affecting uptake and associated productivity improvements. These activities will seek to highlight the gaps between current-practice and best-practice which are impacting on widespread adoption of BIM/VDC and IPD. Early findings will be discussed with intended outcomes of this research being used to: inform a national public procurement strategy; provide guidelines for new contractual frameworks; and contribute to closing skill gaps. Keywords: building information modeling (BIM); virtual design and construction (VDC); integrated project delivery (IPD); transport infrastructure; Australia; procurement

Emotion recognition of static and dynamic faces in autism spectrum disorder

There is substantial evidence for facial emotion recognition (FER) deficits in autism spectrum disorder (ASD). The extent of this impairment, however, remains unclear, and there is some suggestion that clinical groups might benefit from the use of dynamic rather than static images. High-functioning individuals with ASD (n = 36) and typically developing controls (n = 36) completed a computerised FER task involving static and dynamic expressions of the six basic emotions. The ASD group showed poorer overall performance in identifying anger and disgust and were disadvantaged by dynamic (relative to static) stimuli when presented with sad expressions. Among both groups, however, dynamic stimuli appeared to improve recognition of anger. This research provides further evidence of specific impairment in the recognition of negative emotions in ASD, but argues against any broad advantages associated with the use of dynamic displays.