Design and implement of a multi-channel electrophysiological stimulation software

Has done research for the analysis and design of software evaluation clinical practice assessment (PKL / PKN) WEB based on the Diploma Program Radiodiagnostic and Radiotherapy Techniques Semarang. Needs analysis has been conducted for designing software evaluation clinical practice assessment (PKL / PKN) Web-based programming using PHP and MySQL. Analyses were performed with several stages of system analysis, analysis of the weaknesses of the old system based PIECES, a new system needs analysis, feasibility analysis and design of software systems sistem.Desain done with methods for object-oriented programming (Object Oriented Programming) created using the Unified Modeling Language (UML) that is using the use case, the database and interface design. With the analysis and design of the software, will be developed (development) and monitoring and evaluation in the next stage of research.

Research on artificial neural networks (ANNs) has been carried out for more than five decades. A renewed interest appeared in the 80's with the finding of powerful models like J. Hopfield's recurrent networks, T. Kohonen's self-organizing feature maps, and the back-propagation rule. At that time, there was no platform that was at the same time versatile enough for any ANN model to be implemented and fast enough to solve large problems. Super-computers were the sole exception to this rule, but were prohibitively expensive for most applications. However, both research scientists and application engineers clearly identified the need for such a computing power. This triggered many projects in the field. In parallel, research on multi-processor systems started during the 60's. Systolic arrays have been proposed in 1979 as a means to fully exploit the possibilities of VLSI. Two previous theses, by F. Blayo and C. Lehmann, have studied the use of bi-dimensional systolic arrays for neural computation. At first, the presented system, called GENES, has been designed for the Hopfield model. Extensions to other ANNs have also been proposed. The goal of the present thesis is to study, design, build, and analyze an efficient accelerator for neural computation. In a first step, the GENES architecture has been extended towards generality and efficiency. This includes a thorough analysis of ANN models, of other neural computers, and of previous GENES implementations. The result of this work is the GENES IV integrated circuit, whose architecture has been co-designed by P. Ienne and the author. The main part of this thesis discusses the architecture, the design and the analysis of the MANTRA I machine, a neural computer based on a GENES IV array with up to 40 × 40 processing elements (PEs). The delta rule (and hence the Perceptron and Adaline rules), the back-propagation rule, the Hopfield model, and the Kohonen model can be implemented on this system. Although not a generic system, such a machine may be regarded as a multi-model neural computer. A prototype has been running for a year and is used daily by software designers. Several novel features distinguish the MANTRA I machine from other neural systems. First, it belongs to the few existing neural computers, contrary to the majority of implementations, which are specific to an application or to an algorithm. The machine does not hard-wire any algorithm, but provides the necessary primitives to implement the target models. This is a key feature for research, since several algorithms or versions of an algorithm can be tested on a problem. It is an important aspect for applications as well, because different ANN models are often cascaded to solve a problem. The GENES IV array — that is, the computing core of the MANTRA I machine — features synapse-level parallelism (i.e., one real or virtual PE is allocated per synapse or neural connection), while most other systems exploit only neuron-level parallelism (i.e., one PE per neuron). Hence, this system aims at a much finer parallelism grain and is well suited for massively parallel architectures. The problem size that can be computed by a neural accelerator should not be limited by the hardware (except for memory size). Therefore, it is essential to support time-sharing of PEs. On the MANTRA I machine, this is achieved by the concept of virtual arrays. Matrices are divided into sub-matrices that can be mapped onto the physical array, which is then time-shared among them. An efficient mechanism has been implemented to swap sub-matrices in background, while some other computation is performed. Since systolic arrays are pipelined systems, it is important to avoid emptying and re-filling them too often, in order to keep the hardware utilization rate high. Therefore, a systolic instruction flow has been implemented, so that each instruction follows the data for which it has been issued. Like any SIMD system, the MANTRA I machine is composed of a parallel or SIMD module and a control module. The SIMD module consists of the GENES IV array and a set of dedicated units designed for the computation that scales with the number of neurons and would poorly fit on a bi-dimensional array. A complex system of FIFOs and memories sustains the required input/output streams for the systolic array. The control module is a complete SISD system. Its tasks are (1) to control the SIMD module by dispatching instructions, (2) to manage data input and output, (3) to communicate with the external world, and (4) to perform data pre- and post-processing. The SIMD instructions are of the very long instruction word (VLIW) type. Synchronization between the two modules is achieved by an instruction FIFO. The performance of the MANTRA I machine has been analyzed using the delta rule. Measurements show that the sustained performance is very close to its peak value, as long as the problem fits in the memory banks connected to the GENES IV array. Experiments have also been run to investigate the impact of the constraints imposed by the hardware on the convergence of algorithms. Finally, the use of systolic arrays as neural accelerators is discussed in the light of the experience acquired with the GENES IV array and the MANTRA I machine. The weaknesses of the machine are analyzed, and several solutions are proposed to avoid them in a future design. A general discussion of the future of neural computers concludes this thesis.

Objective To investigate the physiological function of the isolated rat retina with a multi-electrode array (MEA) system,and develop a more comprehensive method to evaluate retinal function in animals.Methods In this experimental study,retinas were isolated from 6 Sprague-Dawley (SD) rats,and placed into the recording chamber with the ganglion cell layer facing the biochip electrode array.Retinas were perfused with aerated Ringer's solution for 15 minutes before recording.Then light-evoked or electrical current-evoked responses of the retinal cells were recorded with an MEA system.The obtained data were analyzed with a Shapiro-Wilk test,and the values were presented as a mean±standard deviation.Results Typical light-evoked responses were successfully recorded.The amplitude of the field potential became higher as the luminance increased (＜256 cd/cm2).The results also showed that the off-light responses were obtained when the duration of the light stimulus was changed from 6 to 10 seconds.The light-off response was a low amplitude negative wave at the offset of the light stimulus.Moreover,according to the peristimulus time histograms (PSTHs) and raster plots of individual units,the retinal ganglion cells (RGCs) were categorized as either ON,OFF,or ON-OFF.In addition,the responses of RGCs evoked by electrical current usually occurred within 50 ms post stimulus.Conclusion The MEA can be used to assess the retinal function of animals more comprehensively from different neurons (photoreceptor,bipolar cell and RGC). Key words: Multi-electrode recording; Electrophysiology,visual; Retina; Rats,Sprague-Dawley

This thesis is an examination of the practice of software design amongst professional Australian software architects. It is based on a qualitative analysis of the data arising from transcripts of in-depth interviews with twenty-four software architects and two qualitative case studies of software-architectural design within large Australian organisations. The thesis argues that the practice of software design can only be understood in a holistic sense via a pluralist perspective, and that a constructivist philosophical approach is necessary to account for the practice of software design in a meaningful way. This argument discredits rationalism and by implication modernism as inappropriate philosophical bases for the universal observation, description and comprehension of the practice of software design. The motivation for pursuing this line of investigation is twofold. Firstly, the research seeks to explicate rich and descriptive accounts of the practice of software design in Australian business and industry contexts via an interpretivist research paradigm. Secondly, it attempts to explain the apparently a-rational behaviours of professional software architects in order to separate the practitioner from a sense of inadequacy or failure that follows from the universal imposition of rationalistic design methods and paradigms. The thesis pursues these goals by attempting to fit a situated model of design to the accounts of the participants. Structuring the research process and the rich narratives that emerge from the qualitative analysis is achieved using four philosophical perspectives—rationalism, pragmatism, criticalism and radicalism. The research delivers original findings on how practicing software architects negotiate requirements in the light of known solutions, how they are bound by perspective and paradigm, and the mechanics of their personal design processes. Through these descriptions of activity, the architect is revealed as an arranger of context and situation so as to constitute an environment in which to design tacitly. The thesis concludes that a situated perspective is necessary to understand the practice of software design.

Reconfigurable logic gates in biological crossbar neural networks using STDP learning.

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Photopatterning of self-assembled poly (ethylene) glycol monolayer for neuronal network fabrication

Understanding the mechanisms of neuronal network activity under hypoxic stress is crucial for unraveling the complexities of cerebral ischemia and identifying new treatment targets. In my dissertation, I investigated how hypoxia impacts neuronal functionality in human- and rat-derived neuronal networks cultured on micro-electrode arrays (MEAs) and explored potential treatments to mitigate hypoxia-induced damage.<br/><br/>My findings demonstrate that both human and rat neuronal networks exhibit vulnerability to hypoxia, showing impaired activity and decreased cell viability. I discovered that stimulation of neuronal network activity during hypoxic exposure improves post-hypoxia network recovery, suggesting a potential neuroprotective mechanism. Additionally, I found that cooling neuronal networks during hypoxia preserves functionality, supporting its role as a therapeutic strategy to minimize hypoxic damage.<br/><br/>These results provide insights into how neuronal networks respond to oxygen deprivation and highlight the translational potential of MEA technology in modeling hypoxia-related disorders. By leveraging human-derived neuronal networks, this dissertation paves the way for future in vitro investigations of hypoxia-induced pathophysiology and offers a platform for screening potential neuroprotective interventions.<br/><br/>Further research should explore the molecular underpinnings of these protective mechanisms and assess how targeted pharmacological treatments may enhance neuronal network recovery post-hypoxia. This work establishes human in vitro models on MEA as valuable tools for studying neuronal network dysfunction and contributes to advancing therapeutic approaches for hypoxia-related brain injuries.

Measurement of the activity of human pluripotent stem cell (hPSC)-derived neuronal networks with microelectrode arrays (MEAs) plays an important role in functional in vitro brain modelling and in neurotoxicological screening. The previously reported hPSC-derived neuronal networks do not, however, exhibit repeatable, stable functional network characteristics similar to rodent cortical cultures, making the interpretation of results difficult. In earlier studies, microtunnels have been used both to control and guide cell growth and amplify the axonal signals of rodent neurons. The aim of the current study was to develop tunnel devices that would facilitate signalling and/or signal detection in entire hPSC-derived neuronal networks containing not only axons, but also somata and dendrites. Therefore, MEA-compatible polydimethylsiloxane (PDMS) tunnel devices with 8 different dimensions were created. The hPSC-derived neurons were cultured in the tunnel devices on MEAs, and the spontaneous electrical activity of the networks was measured for 5 weeks. Although the tunnel devices improved the signal-to-noise ratio only by 1.3-fold at best, they significantly increased the percentage of electrodes detecting neuronal activity (52–100%) compared with the controls (27%). Significantly higher spike and burst counts were also obtained using the tunnel devices. Neuronal networks inside the tunnels were amenable to pharmacological manipulation. The results suggest that tunnel devices encompassing the entire neuronal network can increase the measured spontaneous activity in hPSC-derived neuronal networks on MEAs. Therefore, they can increase the efficiency of functional studies of hPSC-derived networks on MEAs.

A CMOS neuroelectronic interface based on two-dimensional transistor arrays with monolithically-integrated circuitry

We propose a case study where a familiar but very complex and intrinsically woven bio-computing system--the blood clotting cascade--is specified using methods from software design known as object-oriented design (OOD). The specifications involve definition and inheritance of classes and methods and use design techniques from the most widely used OOD-language: the Unified Modeling Language (UML), as well as its Real-Time-UML extension. First, we emphasize the needs for a unified methodology to specify complex enough biological and biochemical processes. Then, using the blood clotting cascade as a example, we define the class diagrams which exhibit the static structure of procoagulant factors of proenzyme-enzyme conversions, and finally we give a dynamic model involving events, collaboration, synchronization and sequencing. We thus show that OOD can be used in fields very much beyond software design, gives the benefit of unified and sharable descriptions and, as a side effect, automatic generation of simulation software.

In the digital platform economy, individual freelance workers are matched to their temporary employers thorough online systems. Workers interact with platform firms individually, undermining collective action and hence worker power. This is an issue for policy, as these workers do not have the protections afforded to those in traditional industries. The platform economy has also enabled open source, where the software architect creates a boundary around the software code they accept from a distributed group of contributors. The role of the software architect raises interesting questions about power in what can be seen as a form of networked organisation. Open source can be viewed as a narrative of software code and discussions about it that create a boundary around the project. Open source can also be framed as a business model, where value created by contributors is captured by the software architect for the benefit of both contributors and users. Business models can be viewed as a narrative that can both express and create a desired future for the entrepreneur. The potential of open source to inform narrative forms of business model is the research area. Taking a social constructionist perspective, this study used workshop and participant observation techniques to engage with the founders and other stakeholders in three case study organisations. The empirical contribution is that a narrative form of open source business model can have a power-balanced structure through a discursive process of boundary management. The methodological contribution is that annotated portfolio techniques can reveal an entrepreneur’s business model design from ethnographic data. The theoretical contribution is the importance of conceptual integrity to business models as well as to software engineering. The issue of conceptual integrity can be explored further in future research on factors in business model success.

Microelectrode Array (MEA) devices are well established platforms for biosensing applications, however, limitations in electrode materials and cell coupling to electrodes still exist. Signal-to-noise ratio (SNR), a fabrication limitation, can be improved by reducing the impedance of the microelectrodes without increasing their physical size using conductive nanomaterials. Platinum is a well-studied conductive material that has been determined to be compatible with MEA devices, contains high electronic conductivity, is non-toxic to cells and has excellent catalytic activity. Nano-porous platinum, as compared to pure platinum, has larger surface area enabled by nano-scale definition, and as a result can lower the impedance of microelectrodes. Therefore, in this study nano-porous platinum was electroplated onto thin film gold electrodes to increase SNR in a single-well MEA device. Numerous commercial and research grade MEAs are available and have been subject to for various applications such as disease modeling and pharmaceutical screening. Although high densities of cells can increase the probability of cell-electrode coupling, only signals near electrodes will be detected. Our approach introduces a method of precise patterning of cells on electrodes to increase the probability of cell-electrode coupling and reducing inaccuracies and expenses associated with cell plating. The single-well MEA glass die was designed and fabricated to contain 64 microelectrodes (30 µm diameter with a pitch of 200 µm) and 4 internal on-chip reference electrodes. The MEA glass die fabrication was performed on a 4-inch, 500 µm thick glass wafer. First, metal traces composed of titanium and gold were deposited using lift-off lithography. Subsequently, 5 µm of SU-8 was spin coated and defined as an insulation layer. A separate printed circuit board (PCB) was designed and fabricated to contain 72 contact pads and routing traces. The biocompatible epoxy 353ND was used to package the glass die and PCB in specific orientations determined by alignment markers. Ball bonding with 20 µm diameter gold wire was used to wirebond the glass die to the PCB. A packaging technique was developed that would allow the characterization of key properties of the MEA. This technique involved using copper wire, 100 µm in diameter, and attaching it to the contact pads on the backside of PCBs using a conductive epoxy. Finally, a polystyrene culture well and lid were attached to the MEA using the epoxy, 353ND. Nano-Porous platinum electroplating solution was prepared with a combination of chloroplantinic acid, HCl and lead acetate, all diluted in DI water. Fully packaged devices containing approximately 3 mL of electrolyte were placed within the Axion BioSystems Muse for nano-porous platinum electrodeposition, utilizing the custom Application Specific Integrated Circuit (ASIC) in the system at room temperature. The nano-porous platinum electroplated devices were subsequently characterized using electrical impedance spectroscopy and cyclic voltammetry against the control devices, which contained gold electrodes. The impedance of each device was measured across a scanned frequency range of 10 Hz-100 kHz between the microelectrode, the internal reference electrode and cellular conductive media. The impedance of the nano-porous platinum devices is an order of magnitude lower than the devices with gold electrodes. Cyclic voltammograms were obtained at a scan rate of 20 mV/s in the range from -0.28 to 1.2 V vs. Ag/AgCl. RMS noise comparison between nano-porous platinum electroplated devices and control devices (gold electrodes) was determined using the Muse system and Axion’s Integrated Studio (AxIS) software. Biosensing applications for the devices were explored using electrogenic cells in combination with a precise plating technique. As depicted in Figure 1, cells were positioned in a pattern on and around electrodes to increase the probability of cell-electrode coupling. The electrical response was obtained and analyzed using the Muse system and AxIS software. SNR of action potentials recorded from cells growing on devices enhanced with nano-porous platinum electrodeposition and cells on control devices with gold electrodes were compared. Activity within neuronal networks / beat frequencies of cell patches on electrodes were monitored over the course of 2-3 weeks. The methods explored in this study not only decreases impedance of microelectrodes to increase SNR but also increases cell-electrode coupling by warranting the placement of cells next or on the electrodes by precision patterning. Future studies will aim to optimize electrode sensitivity using novel electrode materials, the porosity of different materials, and characterization using emerging analytical methods. Eventually these devices will provide in vitro systems to monitor both acute and chronic effects of drugs and toxins as well as to perform functional studies under physiological or induced pathophysiological conditions that mimic in vivo damages. Figure 1: Electrogenic cells patterned near nano-porous platinum electrode Figure 1

Classical cases of developmental neurotoxicity (DNT) in humans and advances in risk assessment methods did not prevent the emergence of new chemicals with (suspected) DNT potential. Exposure to these chemicals may be related to the increased worldwide incidence of learning and neurodevelopmental disorders in children. DNT is often investigated in a traditional manner (in vivo using large numbers of experimental animals), whereas development of in vitro methods for DNT reduces animal use and increases insight into cellular and molecular mechanisms of DNT. Several essential neurodevelopmental processes, including proliferation, migration, differentiation, formation of axons and dendrites, synaptogenesis, and apoptosis, are already being evaluated in vitro using biochemical and morphological endpoints. Yet, investigation of chemical-induced effects on the development of functional neuronal networks, including network formation, inter- and intracellular signaling and neuronal network function, is underrepresented in DNT testing. This view therefore focuses on in vitro models and innovative experimental approaches for functional DNT testing, ranging from optical and electrophysiological measurements of intra- and intercellular signaling in neural stem/progenitor cells to measurements of network activity in neuronal networks using multielectrode arrays. The development of functional DNT assays will strongly support the decision-making process for measures to prevent potential chemical-induced adverse effects on neurodevelopment and cognition in humans. We therefore argue that for risk assessment, biochemical and morphological approaches should be complemented with investigations of neuronal (network) functionality.

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