Efficient Genotyping of KRAS Mutant Non-Small Cell Lung Cancer Using a Multiplexed Droplet Digital PCR Approach.

Droplet digital PCR (ddPCR) can be used to detect low frequency mutations in oncogene-driven lung cancer. The range of KRAS point mutations observed in NSCLC necessitates a multiplex approach to efficient mutation detection in circulating DNA. Here we report the design and optimisation of three discriminatory ddPCR multiplex assays investigating nine different KRAS mutations using PrimePCR™ ddPCR™ Mutation Assays and the Bio-Rad QX100 system. Together these mutations account for 95% of the nucleotide changes found in KRAS in human cancer. Multiplex reactions were optimised on genomic DNA extracted from KRAS mutant cell lines and tested on DNA extracted from fixed tumour tissue from a cohort of lung cancer patients without prior knowledge of the specific KRAS genotype. The multiplex ddPCR assays had a limit of detection of better than 1 mutant KRAS molecule in 2,000 wild-type KRAS molecules, which compared favourably with a limit of detection of 1 in 50 for next generation sequencing and 1 in 10 for Sanger sequencing. Multiplex ddPCR assays thus provide a highly efficient methodology to identify KRAS mutations in lung adenocarcinoma.

“Digital Diagnostics and Communication (DDC) system” Redesigning the Emergency Ambulance

During the development of a new treatment space for the UK emergency ambulance participatory observations with front-line clinicians revealed the need for an integrated patient monitoring, communication and navigation system. The research identified the different information touch-points and requirements through modes of use analysis, day-in-the-life study and simulation workshops with clinicians. Emergency scenario and role-play with paramedics identified 5 distinct ambulance modes of use. Information flow diagrams were created and checked by paramedics and digital User Interface (UI) wireframes were developed and evaluated by clinicians during clinical evaluations. Feedback from clinicians defined UI design specification further leading to a final design proposal. This research was a further development from the 2007 EPSRC funded “Smart Pods” project. The resulting interactive prototype was co-designed in collaboration with ambulance crews and provides a vision of what could be achieved by integrating well-proven IT technologies and protocols into a package relevant in the emergency medicine field. The system has been reviewed by over 40 ambulance crews and is part of a newly co-designed ambulance treatment space.

Monitoring sandy shores morphologies by DGPS: a practical tool to generate digital elevation models

The highly dynamic nature of some sandy shores with continuous morphological changes require the development of efficient and accurate methodological strategies for coastal hazard assessment and morphodynamic characterisation. During the past decades, the general methodological approach for the establishment of coastal monitoring programmes was based on photogrammetry or classical geodetic techniques. With the advent of new geodetic techniques, space-based and airborne-based, new methodologies were introduced in coastal monitoring programmes. This paper describes the development of a monitoring prototype that is based on the use of global positioning system (GPS). The prototype has a GPS multiantenna mounted on a fast surveying platform, a land vehicle appropriate for driving in the sand (four-wheel quad). This system was conceived to perform a network of shore profiles in sandy shores stretches (subaerial beach) that extend for several kilometres from which high-precision digital elevation models can be generated. An analysis of the accuracy and precision of some differential GPS kinematic methodologies is presented. The development of an adequate survey methodology is the first step in morphodynamic shore characterisation or in coastal hazard assessment. The sample method and the computational interpolation procedures are important steps for producing reliable three-dimensional surface maps that are real as possible. The quality of several interpolation methods used to generate grids was tested in areas where there were data gaps. The results obtained allow us to conclude that with the developed survey methodology, it is possible to Survey sandy shores stretches, under spatial scales of kilometers, with a vertical accuracy of greater than 0.10 m in the final digital elevation models.

Cosmic Topologies of Imitation: From the Horror of Digital Autotoxicus to the Auto-Toxicity of the Social

This article expands on an earlier concept of horror autotoxicus linked to digital contagions of spam and network Virality.1 It aims to present, as such, a broader conception of cosmic topologies of imitation (CTI) intended to better grasp the relatively new practices of social media marketing. Similar to digital autotoxicity, CTI provide the perfect medium for sharing while also spreading contagions that can potentially contaminate the medium itself. However, whereas digital contagions are perhaps limited to the toxicity of a technical layer of information viruses, the contagions of CTI are an all pervasive auto-toxicity which can infect human bodies and technologies increasingly in concert with each other. This is an exceptional autotoxicus that significantly blurs the immunological line of exemption between self and nonself, and potentially, the anthropomorphic distinction between individual self and collective others.

Mudança dos processos de negócios e adequação da TI nas empresas em decorrência da implantação do sistema público de escrituração digital SPED: um estudo de casos múltiplos

Companies have always been organized by processes, often imperceptible to its employees. With the advancement of technology, organizational processes currently run an organization through computers, and thus generate immediate information that is available to each sector. With the objective of seeking business information in real time, the government created the SPED - Public System of Digital, which involves three subsystems, which are the Electronic Invoice, Digital Accounting Bookkeeping and Digital Tax Bookkeeping. This system is revolutionizing the business structures when gathering, in an innovative way, all information and interlinked business processes. For the implementation of SPED, a revision in the organizational processes is required, since the information is generated and is sent online to the government, without mistakes. Thus the study aimed to analyze the change brought about by the implementation of the Public System of Digital SPED in the main business processes. In order to do so, we have performed a multiple case study involving three companies in the state of Para, two operate in wholesale and one explores agribusiness. The Data collection was performed by accounting professionals, IT and managers. According to the results obtained, it was found that in two companies, the IT infrastructure was capable of deploying the new system without major problems, while one company had more difficulties to cope with the new system. However, all companies had to examine its processes to make the customizations needed to fit. It was also observed that there is no IT Governance in two companies. Therefore, we recommend the use of an appropriate model, not only for the implementation of SPED, but as a way to manage and extract better results from investment in information technology

Optimization of a multielectrode array (MEA)-based approach to study the impact of Aβ on the SH-SY5Y cell line

The human brain stores, integrates, and transmits information recurring to millions of neurons, interconnected by countless synapses. Though neurons communicate through chemical signaling, information is coded and conducted in the form of electrical signals. Neuroelectrophysiology focus on the study of this type of signaling. Both intra and extracellular approaches are used in research, but none holds as much potential in high-throughput screening and drug discovery, as extracellular recordings using multielectrode arrays (MEAs). MEAs measure neuronal activity, both in vitro and in vivo. Their key advantage is the capability to record electrical activity at multiple sites simultaneously. Alzheimer’s disease (AD) is the most common neurodegenerative disease and one of the leading causes of death worldwide. It is characterized by neurofibrillar tangles and aggregates of amyloid-β (Aβ) peptides, which lead to the loss of synapses and ultimately neuronal death. Currently, there is no cure and the drugs available can only delay its progression. In vitro MEA assays enable rapid screening of neuroprotective and neuroharming compounds. Therefore, MEA recordings are of great use in both AD basic and clinical research. The main aim of this thesis was to optimize the formation of SH-SY5Y neuronal networks on MEAs. These can be extremely useful for facilities that do not have access to primary neuronal cultures, but can also save resources and facilitate obtaining faster high-throughput results to those that do. Adhesion-mediating compounds proved to impact cell morphology, viability and exhibition of spontaneous electrical activity. Moreover, SH-SY5Y cells were successfully differentiated and demonstrated acute effects on neuronal function after Aβ addition. This effect on electrical signaling was dependent on Aβ oligomers concentration. The results here presented allow us to conclude that the SH-SY5Y cell line can be successfully differentiated in properly coated MEAs and be used for assessing acute Aβ effects on neuronal signaling.

Security through Obscurity: Layout Obfuscation of Digital Integrated Circuits using Don't Care Conditions

Contemporary integrated circuits are designed and manufactured in a globalized environment leading to concerns of piracy, overproduction and counterfeiting. One class of techniques to combat these threats is circuit obfuscation which seeks to modify the gate-level (or structural) description of a circuit without affecting its functionality in order to increase the complexity and cost of reverse engineering. Most of the existing circuit obfuscation methods are based on the insertion of additional logic (called “key gates”) or camouflaging existing gates in order to make it difficult for a malicious user to get the complete layout information without extensive computations to determine key-gate values. However, when the netlist or the circuit layout, although camouflaged, is available to the attacker, he/she can use advanced logic analysis and circuit simulation tools and Boolean SAT solvers to reveal the unknown gate-level information without exhaustively trying all the input vectors, thus bringing down the complexity of reverse engineering. To counter this problem, some ‘provably secure’ logic encryption algorithms that emphasize methodical selection of camouflaged gates have been proposed previously in literature [1,2,3]. The contribution of this paper is the creation and simulation of a new layout obfuscation method that uses don't care conditions. We also present proof-of-concept of a new functional or logic obfuscation technique that not only conceals, but modifies the circuit functionality in addition to the gate-level description, and can be implemented automatically during the design process. Our layout obfuscation technique utilizes don’t care conditions (namely, Observability and Satisfiability Don’t Cares) inherent in the circuit to camouflage selected gates and modify sub-circuit functionality while meeting the overall circuit specification. Here, camouflaging or obfuscating a gate means replacing the candidate gate by a 4X1 Multiplexer which can be configured to perform all possible 2-input/ 1-output functions as proposed by Bao et al. [4]. It is important to emphasize that our approach not only obfuscates but alters sub-circuit level functionality in an attempt to make IP piracy difficult. The choice of gates to obfuscate determines the effort required to reverse engineer or brute force the design. As such, we propose a method of camouflaged gate selection based on the intersection of output logic cones. By choosing these candidate gates methodically, the complexity of reverse engineering can be made exponential, thus making it computationally very expensive to determine the true circuit functionality. We propose several heuristic algorithms to maximize the RE complexity based on don’t care based obfuscation and methodical gate selection. Thus, the goal of protecting the design IP from malicious end-users is achieved. It also makes it significantly harder for rogue elements in the supply chain to use, copy or replicate the same design with a different logic. We analyze the reverse engineering complexity by applying our obfuscation algorithm on ISCAS-85 benchmarks. Our experimental results indicate that significant reverse engineering complexity can be achieved at minimal design overhead (average area overhead for the proposed layout obfuscation methods is 5.51% and average delay overhead is about 7.732%). We discuss the strengths and limitations of our approach and suggest directions that may lead to improved logic encryption algorithms in the future. References: [1] R. Chakraborty and S. Bhunia, “HARPOON: An Obfuscation-Based SoC Design Methodology for Hardware Protection,” IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems, vol. 28, no. 10, pp. 1493–1502, 2009. [2] J. A. Roy, F. Koushanfar, and I. L. Markov, “EPIC: Ending Piracy of Integrated Circuits,” in 2008 Design, Automation and Test in Europe, 2008, pp. 1069–1074. [3] J. Rajendran, M. Sam, O. Sinanoglu, and R. Karri, “Security Analysis of Integrated Circuit Camouflaging,” ACM Conference on Computer Communications and Security, 2013. [4] Bao Liu, Wang, B., "Embedded reconfigurable logic for ASIC design obfuscation against supply chain attacks,"Design, Automation and Test in Europe Conference and Exhibition (DATE), 2014 , vol., no., pp.1,6, 24-28 March 2014.

Rational Function Interpolation of Electromagnetic Transfer Functions of High-Speed Interconnect Systems from Discrete Time-Domain and Frequency-Domain Data

We present new methodologies to generate rational function approximations of broadband electromagnetic responses of linear and passive networks of high-speed interconnects, and to construct SPICE-compatible, equivalent circuit representations of the generated rational functions. These new methodologies are driven by the desire to improve the computational efficiency of the rational function fitting process, and to ensure enhanced accuracy of the generated rational function interpolation and its equivalent circuit representation. Toward this goal, we propose two new methodologies for rational function approximation of high-speed interconnect network responses. The first one relies on the use of both time-domain and frequency-domain data, obtained either through measurement or numerical simulation, to generate a rational function representation that extrapolates the input, early-time transient response data to late-time response while at the same time providing a means to both interpolate and extrapolate the used frequency-domain data. The aforementioned hybrid methodology can be considered as a generalization of the frequency-domain rational function fitting utilizing frequency-domain response data only, and the time-domain rational function fitting utilizing transient response data only. In this context, a guideline is proposed for estimating the order of the rational function approximation from transient data. The availability of such an estimate expedites the time-domain rational function fitting process. The second approach relies on the extraction of the delay associated with causal electromagnetic responses of interconnect systems to provide for a more stable rational function process utilizing a lower-order rational function interpolation. A distinctive feature of the proposed methodology is its utilization of scattering parameters. For both methodologies, the approach of fitting the electromagnetic network matrix one element at a time is applied. It is shown that, with regard to the computational cost of the rational function fitting process, such an element-by-element rational function fitting is more advantageous than full matrix fitting for systems with a large number of ports. Despite the disadvantage that different sets of poles are used in the rational function of different elements in the network matrix, such an approach provides for improved accuracy in the fitting of network matrices of systems characterized by both strongly coupled and weakly coupled ports. Finally, in order to provide a means for enforcing passivity in the adopted element-by-element rational function fitting approach, the methodology for passivity enforcement via quadratic programming is modified appropriately for this purpose and demonstrated in the context of element-by-element rational function fitting of the admittance matrix of an electromagnetic multiport.

Low-power high-performance SAR ADC design with digital calibration techniques

This dissertation presents the design of three high-performance successive-approximation-register (SAR) analog-to-digital converters (ADCs) using distinct digital background calibration techniques under the framework of a generalized code-domain linear equalizer. These digital calibration techniques effectively and efficiently remove the static mismatch errors in the analog-to-digital (A/D) conversion. They enable aggressive scaling of the capacitive digital-to-analog converter (DAC), which also serves as sampling capacitor, to the kT/C limit. As a result, outstanding conversion linearity, high signal-to-noise ratio (SNR), high conversion speed, robustness, superb energy efficiency, and minimal chip-area are accomplished simultaneously. The first design is a 12-bit 22.5/45-MS/s SAR ADC in 0.13-μm CMOS process. It employs a perturbation-based calibration based on the superposition property of linear systems to digitally correct the capacitor mismatch error in the weighted DAC. With 3.0-mW power dissipation at a 1.2-V power supply and a 22.5-MS/s sample rate, it achieves a 71.1-dB signal-to-noise-plus-distortion ratio (SNDR), and a 94.6-dB spurious free dynamic range (SFDR). At Nyquist frequency, the conversion figure of merit (FoM) is 50.8 fJ/conversion step, the best FoM up to date (2010) for 12-bit ADCs. The SAR ADC core occupies 0.06 mm2, while the estimated area the calibration circuits is 0.03 mm2. The second proposed digital calibration technique is a bit-wise-correlation-based digital calibration. It utilizes the statistical independence of an injected pseudo-random signal and the input signal to correct the DAC mismatch in SAR ADCs. This idea is experimentally verified in a 12-bit 37-MS/s SAR ADC fabricated in 65-nm CMOS implemented by Pingli Huang. This prototype chip achieves a 70.23-dB peak SNDR and an 81.02-dB peak SFDR, while occupying 0.12-mm2 silicon area and dissipating 9.14 mW from a 1.2-V supply with the synthesized digital calibration circuits included. The third work is an 8-bit, 600-MS/s, 10-way time-interleaved SAR ADC array fabricated in 0.13-μm CMOS process. This work employs an adaptive digital equalization approach to calibrate both intra-channel nonlinearities and inter-channel mismatch errors. The prototype chip achieves 47.4-dB SNDR, 63.6-dB SFDR, less than 0.30-LSB differential nonlinearity (DNL), and less than 0.23-LSB integral nonlinearity (INL). The ADC array occupies an active area of 1.35 mm2 and dissipates 30.3 mW, including synthesized digital calibration circuits and an on-chip dual-loop delay-locked loop (DLL) for clock generation and synchronization.

Red Bull, un ejemplo paradigmático de las nuevas estrategias de comunicación de las marcas en el entorno digital

Introducción: En la presente investigación nos vamos a centrar en los contenidos on line que ofrece la marca Red Bull ya sea a través de su web www.redbull.tv o de su App Red Bull TV. Red Bull como marca necesita destacar de entre todo el ruido publicitario, necesita hacerse notar y llegar hasta sus consumidores, pero hoy en día las audiencias están fragmentadas, las audiencias no están sometidas al dictado programático de las televisiones. Cada vez más, y sobre todo en el público joven, que es aquel con el que más se identifica esta marca, es un público activo que genera sus propias parrillas de programación, que busca aquello que realmente quiere ver. Entonces, ¿cómo una marca logra que se le escuche? a través del Rock&Love: sorprender y dar amor. Hipótesis: Nuestra hipótesis de partida es que Red Bull, en la búsqueda de conexión con su público, les ofrece contenidos de su interés que les reafirma en su acercamiento a la marca, y así lograr el Rock&Love. Objetivos: De acuerdo con la hipótesis, son tres los objetivos que van a guiar la presente investigación: el primero, conocer las claves de Red Bull en el entorno digital. El segundo, realizar un análisis de los contenidos utilizados por la marca para aproximarse a sus usuarios teniendo en cuenta los nuevos hábitos de consumo. El tercero, analizar la diferencia de contenidos según el medio en que se difunde. Metodología: Para corroborar o no nuestra hipótesis participaremos del método cualitativo y del método cuantitativo. Las técnicas a utilizar son la observación documental y el análisis de contenido. Conclusiones: Este análisis de contenido Ad Hoc ha permitido la obtención de datos cuantitativos y nos ha facilitado la aproximación a nuestros objetivos de forma cualitativa y de esta forma, se ha logrado dar respuesta a la hipótesis de partida y confirmar que la marca recurre al Rock&Love en los contenidos que muestran a través de las diferentes plataformas de Red Bull TV.

Measurement and Simulation of Suppression Effects in a Buoyant Turbulent Line Fire

An experimental and numerical study of turbulent fire suppression is presented. For this work, a novel and canonical facility has been developed, featuring a buoyant, turbulent, methane or propane-fueled diffusion flame suppressed via either nitrogen dilution of the oxidizer or application of a fine water mist. Flames are stabilized on a slot burner surrounded by a co-flowing oxidizer, which allows controlled delivery of either suppressant to achieve a range of conditions from complete combustion through partial and total flame quenching. A minimal supply of pure oxygen is optionally applied along the burner to provide a strengthened flame base that resists liftoff extinction and permits the study of substantially weakened turbulent flames. The carefully designed facility features well-characterized inlet and boundary conditions that are especially amenable to numerical simulation. Non-intrusive diagnostics provide detailed measurements of suppression behavior, yielding insight into the governing suppression processes, and aiding the development and validation of advanced suppression models. Diagnostics include oxidizer composition analysis to determine suppression potential, flame imaging to quantify visible flame structure, luminous and radiative emissions measurements to assess sooting propensity and heat losses, and species-based calorimetry to evaluate global heat release and combustion efficiency. The studied flames experience notable suppression effects, including transition in color from bright yellow to dim blue, expansion in flame height and structural intermittency, and reduction in radiative heat emissions. Still, measurements indicate that the combustion efficiency remains close to unity, and only near the extinction limit do the flames experience an abrupt transition from nearly complete combustion to total extinguishment. Measurements are compared with large eddy simulation results obtained using the Fire Dynamics Simulator, an open-source computational fluid dynamics software package. Comparisons of experimental and simulated results are used to evaluate the performance of available models in predicting fire suppression. Simulations in the present configuration highlight the issue of spurious reignition that is permitted by the classical eddy-dissipation concept for modeling turbulent combustion. To address this issue, simple treatments to prevent spurious reignition are developed and implemented. Simulations incorporating these treatments are shown to produce excellent agreement with the experimentally measured data, including the global combustion efficiency.

Interaction of Acoustic Waves with a Laminar Line-Flame

A systematic study was conducted to elucidate the effects of acoustic perturbations on laminar diffusion line-flames and the conditions required to cause acoustically-driven extinction. Flames were produced from the fuels n-pentane, n-hexane, n-heptane, n-octane, and JP-8, using fuel-laden wicks. The wicks were housed inside of a burner whose geometry produced flames that approximated a two dimensional flame sheet. The acoustics utilized ranged in frequency between 30-50 Hz and acoustic pressures between 5-50 Pa. The unperturbed mass loss rate and flame height of the alkanes were studied, and they were found to scale in a linear manner consistent with Burke-Schumann. The mass loss rate of hexane-fueled flames experiencing acoustic perturbations was then studied. It was found that the strongest influence on the mass loss rate was the magnitude of oscillatory air movement experienced by the flame. Finally, acoustic perturbations were imposed on flames using all fuels to determine acoustic extinction criterion. Using the data collected, a model was developed which characterized the acoustic conditions required to cause flame extinction. The model was based on the ratio of an acoustic Nusselt Number to the Spalding B Number of the fuel, and it was found that at the minimum speaker power required to cause extinction this ratio was a constant. Furthermore, it was found that at conditions where the ratio was below this constant, a flame could still exist; at conditions where the ratio was greater than or equal to this constant, flame extinction always occurred.

Implementação em FPGA de compensadores de desvios para conversor analógico digital intercalado

This work presents the modeling and FPGA implementation of digital TIADC mismatches compensation systems. The development of the whole work follows a top-down methodology. Following this methodology was developed a two channel TIADC behavior modeling and their respective offset, gain and clock skew mismatches on Simulink. In addition was developed digital mismatch compensation system behavior modeling. For clock skew mismatch compensation fractional delay filters were used, more specifically, the efficient Farrow struct. The definition of wich filter design methodology would be used, and wich Farrow structure, required the study of various design methods presented in literature. The digital compensation systems models were converted to VHDL, for FPGA implementation and validation. These system validation was carried out using the test methodology FPGA In Loop . The results obtained with TIADC mismatch compensators show the high performance gain provided by these structures. Beyond this result, these work illustrates the potential of design, implementation and FPGA test methodologies.

Content and Connectivity in the Age of Digital Libraries

"Behind the world of virtual university is more than a method or system of work, you need to own, develop and master a connectivity structure of both technological and content development in multimedia digital text and then implement teaching methods line. "