THE ROLE OF RECEPTOR TYROSINE KINASE AXL IN PANCREATIC DUCTAL ADENOCARCINOMA AND ITS REGULATION BY HEMATOPOIETIC PROGENITOR KINASE 1

Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive malignancies with less than 5% of five year survival rate. New molecular markers and new therapeutic targets are urgently needed for patients with PDA. Oncogenic receptor tyrosine kinase Axl has been reported to be overexpressed in many types of human malignancies, including diffuse glioma, melanoma, osteosarcoma, and carcinomas of lung, colon, prostate, breast, ovary, esophagus, stomach, and kidney. However, the expression and functions of Axl in PDA are unclear. We hypothesized that Axl contributes to the development and progression of PDA. We examined Axl expression in 54 human PDA samples and their paired benign pancreatic tissue by immunohistochemistry, we found that Axl was overexpressed in 70% of stage II PDAs, but only 22% of benign ducts (P=0.0001). Axl overexpression was associated with higher frequencies of distant metastasis and was an independent prognostic factor for both poor overall and recurrence-free survivals in patients with stage II PDA (p = 0.03 and 0.04). Axl silencing by shRNA in pancreatic cancer cell lines, panc-28 and Panc-1, decreased tumor cell migration and invasion and sensitized PDA cells to apoptosis stimuli such as γ-irradiation and serum starvation. In addition, we found that Axl-mediated Akt and NF-κB activation and up regulation of MMP2 were involved in the invasion, migration and survival of PDA cells. Thus, we demonstrate that Axl plays an important role in the development and progression of PDA. Targeting Axl signaling pathway may represent a new approach for the treatment of PDA. To understand the molecular mechanisms of Axl overexpression in PDA, we found that Axl expression was down-regulated by hematopoietic progenitor kinase 1 (HPK1), a newly identified tumor suppressor in PDA. HPK1 is lost in over 95% of PDAs. Restoration of HPK1 in PDA cells down-regulated Axl expression. HPK1-mediated Axl degradation was inhibited by leupeptin, baflomycin A1, and monensin, suggesting that HPK1-mediated Axl degradation was through endocytosis-lysosome pathway. HPK1 interacted with and phosphorylated dynamin, a critical component of endocytosis pathway. Overexpression of dominant negative form of dynamin blocked the HPK1-mediated Axl degradation. Therefore we concluded that HPK1-mediated Axl degradation was through endocytosis-lysosome pathway and loss of HPK1 expression may contribute to Axl overexpression in PDAs.

The Choosing Healthy Options of Starches (CHOOS) diet and dietary intake self-monitoring for weight loss among adolescent females

Previous research has shown dietary intake self-monitoring, and culturally tailored weight loss interventions to be effective tools for weight loss. Technology can be used to tailor weight loss interventions to better suit adolescents. There is a lack of research to date on the use of personal digital assistants (PDAs) to self-monitor dietary intake among adolescents. The objective of this study was to determine the difference in dietary intake self-monitoring frequency between using a Personal Digital Assistant (PDA) or paper logs as a diet diary in obese adolescent females; and to describe differences in diet adherence, as well as changes in body size and self-efficacy to resist eating. We hypothesized dietary intake self-monitoring frequency would be greater during PDA use than during paper log use. This study was a randomized crossover trial. Participants recorded their diet for 4 weeks: 2 weeks on a PDA and 2 weeks on paper logs. Thirty-four obese females ages 12-20 were recruited for participation. Thirty were included in analyses. Participants recorded more entries/day while using the paper logs (4.10 entries/day ± 0.63) than while using the PDA (3.01 entries/day ±0.75) (p<0.001). Significantly more meals and snacks were skipped during paper log use (0.81/day ± 0.65) than during PDA use (0.23/day ± 0.22) (p=0.011). Changes in body size (BMI, weight, and waist circumference) and self-efficacy to resist eating did not differ significantly between PDA and paper log use. When compared to paper logs, participants felt the PDA was more convenient (p=0.020), looked forward to using the PDA more (p=0.008), and would rather continue using the PDA than the paper logs (p=0.020). The findings of this study indicate use of a PDA as a dietary intake self-monitoring tool among adolescents would not result in increased dietary intake self-monitoring to aid in weight loss. Use of paper logs would result in greater data returned to clinicians, though use of PDAs would likely get adolescents more excited about adhering to recommendations to record their diet. Future research should look at updated communication devices, such as cell phones and other PDAs with additional features, and the role they can play in increasing dietary intake self-monitoring among adolescents.^

Lightweight peer-to-peer secure multi-party VoIP protocol

Multi-party voice-over-IP (MVoIP) services provide economical and convenient group communication mechanisms for many emerging applications such as distance collaboration systems, on-line meetings and Internet gaming. In this paper, we present a light peer-to-peer (P2P) protocol to provide MVoIP services on small platforms like mobile phones and PDAs. Unlike other proposals, our solution is fully distributed and self-organizing without requiring specialized servers or IP multicast support.

Observations in a maternity ward: Usability considerations for EHRs in an interrupt driven environment

With the increasing demand on healthcare systems it is imperative that all care is provided as efficiently and effectively as possible. Technology within the medical domain offers an exciting opportunity to augment work practices in order to meet these needs. This research project explores the implications of the interrupt-driven nature of work in clinical situations on documentation within an environment that increasingly involves electronic health records (EHRs). Midwives in a busy maternity ward were observed and interviewed about the work practices they employed to document information associated with patient care. The results showed that the interrupt-driven nature of the workplace, a feature common to many healthcare settings, led to a tension between the work and the work to document the work. Further, the IT environment in which the information was collected was not designed to cater for frequent interruption of the data entry process. Several recommendations for improving the IT environment are proposed to support health professionals in documenting patient data whilst attending to the interruptions. The recommendations include timeout screens, push technology, use of handheld PDAs, and cues to augment documentation in an interrupted session. Copyright © 2008 RMIT Publishing

FACES E INTERFACES DAS MÚLTIPLAS TELAS: a comunicação nas plataformas audiovisuais digitais

A sociedade é digital e vivencia as benesses, desafios e paradigmas dessa era. As mudanças estão aceleradas e o tempo de adaptação a elas mais curto a cada dia. As relações comunicativas do homem com as máquinas estão se alterando de maneira profunda, com destaque para a multiplicação de telas audiovisuais que permeiam a vida das pessoas, as quais hoje são assessoradas por meio de inúmeros Assistentes Digitais Pessoais (PDAs) e outros displays ubíquos que convergem de forma radical entre si. A profusão tecnológica e apropriação sensorial dos instrumentos contemporâneos são exemplos tangíveis disso. Com tal cenário em primeiro plano, nossa pesquisa propõe contextualizar, descrever e analisar as novas faces e interfaces da comunicação que se materializam nas atuais plataformas audiovisuais digitais, cada vez mais móveis, conectadas e velozes. Dessa forma, empreende-se uma pesquisa exploratória que se valerá prioritariamente de levantamento bibliográfico específico e análise de dados estatísticos. A pesquisa indicou que as múltiplas telas, de fato, estão modificando a dinâmica dos processos comunicativos, os quais precisam ser recompreendidos.

Exploring civil servant resistance to M-government:a story of transition and opportunities in Turkey

The concept of mobility, related to technology in particular, has evolved dramatically over the last two decades including: (i) hardware ranging from walkmans to Ipods, laptops to netbooks, PDAs to 3G mobile phone; (ii) software supporting multiple audio and video formats driven by ubiquitous mobile wireless access, WiMax, automations such as radio frequency ID tracking and location aware services. Against the background of increasing budget deficit, along with the imperative for efficiency gains, leveraging ICT and mobility promises for work related tasks, in a public administration context, in emerging markets, point to multiple possible paths. M-government transition involve both technological changes and adoption to deliver government services differently (e.g. 24/7, error free, anywhere to the same standards) but also the design of digital strategies including possibly competing m-government models, the re-shaping of cultural practices, the creation of m-policies and legislations, the structuring of m-services architecture, and progress regarding m-governance. While many emerging countries are already offering e-government services and are gearing-up for further m-government activities, little is actually known about the resistance that is encountered, as a reflection of civil servants' current standing, before any further macro-strategies are deployed. Drawing on the resistance and mobility literature, this chapter investigates how civil servants' behaviors, in an emerging country technological environment, through their everyday practice, react and resist the influence of m-government transition. The findings points to four main type of resistance namely: i) functional resistance; ii) ideological resistance; iii) market driven resistance and iv) geographical resistance. Policy implication are discussed in the specific context of emerging markets. © 2011, IGI Global.

Towards a web-based progressive handwriting recognition environment for mathematical problem solving

The emergence of pen-based mobile devices such as PDAs and tablet PCs provides a new way to input mathematical expressions to computer by using handwriting which is much more natural and efficient for entering mathematics. This paper proposes a web-based handwriting mathematics system, called WebMath, for supporting mathematical problem solving. The proposed WebMath system is based on client-server architecture. It comprises four major components: a standard web server, handwriting mathematical expression editor, computation engine and web browser with Ajax-based communicator. The handwriting mathematical expression editor adopts a progressive recognition approach for dynamic recognition of handwritten mathematical expressions. The computation engine supports mathematical functions such as algebraic simplification and factorization, and integration and differentiation. The web browser provides a user-friendly interface for accessing the system using advanced Ajax-based communication. In this paper, we describe the different components of the WebMath system and its performance analysis.

Dynamically managing sensed context data

This thesis reports on an investigation of the feasibility and usefulness of incorporating dynamic management facilities for managing sensed context data in a distributed contextaware mobile application. The investigation focuses on reducing the work required to integrate new sensed context streams in an existing context aware architecture. Current architectures require integration work for new streams and new contexts that are encountered. This means of operation is acceptable for current fixed architectures. However, as systems become more mobile the number of discoverable streams increases. Without the ability to discover and use these new streams the functionality of any given device will be limited to the streams that it knows how to decode. The integration of new streams requires that the sensed context data be understood by the current application. If the new source provides data of a type that an application currently requires then the new source should be connected to the application without any prior knowledge of the new source. If the type is similar and can be converted then this stream too should be appropriated by the application. Such applications are based on portable devices (phones, PDAs) for semi-autonomous services that use data from sensors connected to the devices, plus data exchanged with other such devices and remote servers. Such applications must handle input from a variety of sensors, refining the data locally and managing its communication from the device in volatile and unpredictable network conditions. The choice to focus on locally connected sensory input allows for the introduction of privacy and access controls. This local control can determine how the information is communicated to others. This investigation focuses on the evaluation of three approaches to sensor data management. The first system is characterised by its static management based on the pre-pended metadata. This was the reference system. Developed for a mobile system, the data was processed based on the attached metadata. The code that performed the processing was static. The second system was developed to move away from the static processing and introduce a greater freedom of handling for the data stream, this resulted in a heavy weight approach. The approach focused on pushing the processing of the data into a number of networked nodes rather than the monolithic design of the previous system. By creating a separate communication channel for the metadata it is possible to be more flexible with the amount and type of data transmitted. The final system pulled the benefits of the other systems together. By providing a small management class that would load a separate handler based on the incoming data, Dynamism was maximised whilst maintaining ease of code understanding. The three systems were then compared to highlight their ability to dynamically manage new sensed context. The evaluation took two approaches, the first is a quantitative analysis of the code to understand the complexity of the relative three systems. This was done by evaluating what changes to the system were involved for the new context. The second approach takes a qualitative view of the work required by the software engineer to reconfigure the systems to provide support for a new data stream. The evaluation highlights the various scenarios in which the three systems are most suited. There is always a trade-o↵ in the development of a system. The three approaches highlight this fact. The creation of a statically bound system can be quick to develop but may need to be completely re-written if the requirements move too far. Alternatively a highly dynamic system may be able to cope with new requirements but the developer time to create such a system may be greater than the creation of several simpler systems.

Secure and Privacy-aware Data Collection and Processing in Mobile Health Systems

Healthcare systems have assimilated information and communication technologies in order to improve the quality of healthcare and patient's experience at reduced costs. The increasing digitalization of people's health information raises however new threats regarding information security and privacy. Accidental or deliberate data breaches of health data may lead to societal pressures, embarrassment and discrimination. Information security and privacy are paramount to achieve high quality healthcare services, and further, to not harm individuals when providing care. With that in mind, we give special attention to the category of Mobile Health (mHealth) systems. That is, the use of mobile devices (e.g., mobile phones, sensors, PDAs) to support medical and public health. Such systems, have been particularly successful in developing countries, taking advantage of the flourishing mobile market and the need to expand the coverage of primary healthcare programs. Many mHealth initiatives, however, fail to address security and privacy issues. This, coupled with the lack of specific legislation for privacy and data protection in these countries, increases the risk of harm to individuals. The overall objective of this thesis is to enhance knowledge regarding the design of security and privacy technologies for mHealth systems. In particular, we deal with mHealth Data Collection Systems (MDCSs), which consists of mobile devices for collecting and reporting health-related data, replacing paper-based approaches for health surveys and surveillance. This thesis consists of publications contributing to mHealth security and privacy in various ways: with a comprehensive literature review about mHealth in Brazil; with the design of a security framework for MDCSs (SecourHealth); with the design of a MDCS (GeoHealth); with the design of Privacy Impact Assessment template for MDCSs; and with the study of ontology-based obfuscation and anonymisation functions for health data.

Integrating mobile devices into a scalable Grid Computing architecture designed to perform distributed computations

The idea of Grid Computing originated in the nineties and found its concrete applications in contexts like the SETI@home project where a lot of computers (offered by volunteers) cooperated, performing distributed computations, inside the Grid environment analyzing radio signals trying to find extraterrestrial life. The Grid was composed of traditional personal computers but, with the emergence of the first mobile devices like Personal Digital Assistants (PDAs), researchers started theorizing the inclusion of mobile devices into Grid Computing; although impressive theoretical work was done, the idea was discarded due to the limitations (mainly technological) of mobile devices available at the time. Decades have passed, and now mobile devices are extremely more performant and numerous than before, leaving a great amount of resources available on mobile devices, such as smartphones and tablets, untapped. Here we propose a solution for performing distributed computations over a Grid Computing environment that utilizes both desktop and mobile devices, exploiting the resources from day-to-day mobile users that alternatively would end up unused. The work starts with an introduction on what Grid Computing is, the evolution of mobile devices, the idea of integrating such devices into the Grid and how to convince device owners to participate in the Grid. Then, the tone becomes more technical, starting with an explanation on how Grid Computing actually works, followed by the technical challenges of integrating mobile devices into the Grid. Next, the model, which constitutes the solution offered by this study, is explained, followed by a chapter regarding the realization of a prototype that proves the feasibility of distributed computations over a Grid composed by both mobile and desktop devices. To conclude future developments and ideas to improve this project are presented.