Telefon-Nummer: +41 24 557 62 73
Description du projet :
The last decade has witnessed a renewed interest for in vitro approaches in the fields of drug discovery and
toxicity testing. One very promising approach is the use of engineered human neural tissue fabricated from iPS
cells. To ensure the rapidity of the tests in neural tissues the traditional chemical, cytosolic and histologic read-
outs have been replaced by an electrophysiological read-out, i.e. the recording of the electrical activity of
neurons using smart Petri dishes that incorporate electrode arrays. A big challenge for recording such activity
is the very large amount of data generated by the electrode arrays, resulting in cumbersome and long data
analysis to be performed in order to get the final experimental results, and the reliability of the systems.
Within this context, the aim of the SpikeOnChip project is to develop a platform for efficient processing and
storage of neuronal spike activities. It will not only offer recording of observed electrodes (up to 64), but also
an on-chip analysis that will allow to reduce the quantity of data by a factor of 20x, by selecting only the
interesting portions. The platform will be based on a ZedBoard embedding a Zynq (FPGA + ARM processor in
one die). This data reduction will allow to save memory, and as a result allow the system to run autonomously
for a longer period of time. Connection will be supplied by a Wifi link in order to transfer data to a PC, however
gaining autonomy will imply a more reliable system in the sense that if the connection is lost at some point,
data can be stored for up to 3 hours without losing any important information.
Data acquisition will be done by an Intan chip that translates raw voltages from the electrode array onto serial
digital data that is sent to an FPGA. The processing performed on-chip will consist in signal filtering of the raw
data, spike detection, noise rejection, and field potential frequency analysis.
Finally a software will also be developed so as to let a user control the embedded platform and to visualize the
This project will imply a validation stage, performed by biologists, to ensure the system not only works with
respect to the specifications, but is also usable by end users.
Forschungsteam innerhalb von HES-SO:
, Wertenbroek Rick
, Scherwey Roland
, Meury Mike
, Mor Flavio
, Stoppini Luc
, Gachet Daniel
Partenaires académiques: ReDS; hepia inSTI; FR - EIA - Institut iSIS; Thoma Yann, ReDS
Durée du projet:
01.04.2017 - 30.09.2018
Montant global du projet: 143'774 CHF
OFFT; Nano-Tera.CH; HEIG-VD
Description du projet :
Modern therapeutics must benefit from the development and large-scale implementation of convenient, user-friendly, miniaturized, integrated instruments enabling drug concentration monitoring and seamless pharmacokinetically guided dosage individualization. Technological advances during recent years make it possible to envisage a portable system, which would allow to perform drug concentration measurement in patients receiving critical treatments. The device should be offered at affordable cost to specialized clinics, and progressively to general practices or even to the patients themselves (as it is already the case for blood glucose determination). Translation of concentration measurement values into personalized treatment advices requires the integration of efficient and ergonomic computer tools into the system. These need to be coupled with communication capabilities, which are nowadays becoming a standard in many aspects of medical care, in order to be connected to reference pharmacokinetic-parameters databases.
The conception of our Point-Of-Care (POC) system is addressed to respond to three main objectives: (i) perform the measurement of drug concentration in blood samples by an automated and compact analytical setup; (ii) provide the medical doctor with information on the behavior of the patient within the population and accordingly suggest dosage adjustment; (iii) collect drug usage and measurement data into a remote database, enabling further refinements in dosage adjustment procedures. The aim of the TheraPer project is to develop a sample-to-result POC system, which would include all the outlined functions. In particular, the system will be stand-alone and provide communication and elaboration functions in a configurable fashion in order to respond to different application needs.
The TheraPer consortium holds a composite set of know-how and owned technologies to develop each technological component of the system, namely: a miniaturized blood sample preparation device, connected to a compact and low-cost analytical system with electronic readout for determining the drug concentration; an embedded elaboration software framework to determine dosage adjustment, manage population data and connect with remote databases; finally, a flexible and ergonomic graphical user interface to interact with the user at different levels of complexity.
The project relies on the longstanding experience of the Division of Clinical Pharmacology at CHUV in Therapeutic Drug Monitoring (TDM). During the past decade, this group has played a significant role in the development of new monitoring approaches in various fields of therapeutics (HIV, cancer, fungal infections), and it is now internationally regarded as a center of excellence in this domain. The team will contribute to the project by bringing knowledge and practice about drug dosage individualization, along with technical competences in population pharmacokinetic/pharmacodynamic analysis, state of the art tools, and expertise currently used for drug analysis in biological matrices.
The TheraPer project has the potential to contribute to different scientific domains, as granted by the high-impact publication records which resulting from the research work of the partners. Concomitantly, TheraPer will be able to target the development of a reliable prototype within the timeframe of the project, thanks to the outstanding engineering skills and the industrial experience of the consortium.
Dosage individualization is the key to improve cost-effectiveness and efficacy of medical treatments worldwide. For this reason, the TheraPer project raised the interest of the World Health Organization. Indeed, the potential impact of an affordable POC system for TDM in decreasing costs and improving treatment efficacy of HIV in developing countries will be consistent.
Forschungsteam innerhalb von HES-SO:
, Divorne Sandrine
, Rigamonti Roberto
Partenaires académiques: ReDS; Thoma Yann, ReDS
Durée du projet:
01.11.2013 - 31.10.2017
Montant global du projet: 562'250 CHF
KTI - CTI; IOxOS Technologies
Description du projet :
This project aims to develop the Network on Chip (NoC) based FPGA design environment intended to implement the next generation of IOxOS Technologies COTS solutions based on Xilinx UltraScale FPGAs. This innovative concept is developed to guarantee a high-performance data flow within the FPGA, to support PCI Express GEN3, and to provide a high Quality of Service (QoS) to fulfill the real-time application requirements of Physics, Energy, Transport and Mil/Aero industries.
Forschungsteam innerhalb von HES-SO:
, Petraglio Enrico
, Rigamonti Roberto
, Auberson Olivier
Durée du projet:
01.12.2014 - 31.12.2016
Montant global du projet: 261'100 CHF
Description du projet :
La détection précoce au chevet du patient (Point of Care, ou POC) de maladies permet un diagnostic et une intervention plus rapides. Le projet MOVABLE vise à développer un système POC quantitatif pour l'analyse de cellules sanguines via un dispositif de microscopie optique miniaturisé permettant de compter les cellules
d'un certain type, normales ou infectées. Les cellules seront séparées à l'aide de surfaces fonctionnalisées et seront détectées par microscopie en transmission ou en fluorescence. Le traitement d'image sera effectué sur un smartphone, de même que potentiellement la prise d'image, si la première phase d'analyse avalise cette solution. L'ensemble du système se veut être de type POC, de manière à pouvoir être disponible dans des contrées reculées où l'accès aux hopitaux n'est pas possible.
Bien que le système se veuille général, deux applications seront visées: la détection du taux de lymphocytes CD4 pour le suivi du SIDA et la détection précoce de la malaria.
Forschungsteam innerhalb von HES-SO:
, Prim Denis
, Thoma Yann
, Amoos Serge
, Dassatti Alberto
, Condemi Enrico
, Geiser Martial
, Rigamonti Roberto
, Truffer Frédéric
, Kocher Michel
, Schnyder Bruno
, Segura Jean-Manuel
, Pfeifer Marc Emil
Partenaires académiques: VS - Institut Systèmes industriels; ReDS; VS - Institut Technologies du vivant; Thoma Yann, ReDS
Durée du projet:
01.02.2014 - 31.01.2016
Description du projet :
Ezekiel est un outil d'aide pour les médecins et pharmacologues pour le monitoring de concentration de médicament dans le sang. Il vise notamment à faciliter le dosage des médicaments nécessitant une prise quotidienne
Forschungsteam innerhalb von HES-SO:
Durée du projet:
01.06.2011 - 31.10.2013
Montant global du projet: 169'584 CHF
Requérant(e)s: VS - Institut Systèmes industriels, Bianchi Christophe, VS - Institut Systèmes industriels
Description du projet :
Le but du projet est de réaliser un environnement de vérification permettant la mise sur pied rapide d'un banc de test basé sur le langage SystemVerilog, les librairies UVM ainsi qu'une librairie d'IP de vérification de la HES-SO.
L'outil UVE permettra de générer, sur la base d'un banc de test générique et d'une librairie de vérification d'IP, tout un environnement de simulation pour l'utilisateur. Celui-ci n'aura plus qu'à compléter les éléments non existants de la librairie, mais déjà implémentés comme boite noire dans le banc de test, pour réaliser la validation complète de son design. Les éléments de base ainsi que les VIP existants permettront déjà à l'utilisateur de réaliser des simulations sans une connaissance approfondie du langage SystemVerilog et des librairies UVM.
Le langage SystemVerilog ainsi que les méthodologies proposées par la librairie UVM sont relativement complexes à appréhender, notamment pour des ingénieurs venant de l'électronique, car il embarque notamment des notions de programmation orientée objet. UVE permettra donc de s'affranchir de cette compréhension pour la mise au point rapide de bancs de test.
Forschungsteam innerhalb von HES-SO:
, Bianchi Christophe
Partenaires académiques: VS - Institut Systèmes industriels; ReDS; Bianchi Christophe, VS - Institut Systèmes industriels
Durée du projet:
04.12.2011 - 31.01.2013
Montant global du projet: 149'600 CHF
Description du projet :
This project aims at proposing a complete and easy-to-use framework enabling the integration of GPU and FPGA resources communicating through direct PCIe links in the same computational platform. A methodology and the corresponding tools (including software drivers, hardware building blocks and GPU sample code) will be developed and proposed to the community. The availability of such a framework will enable an easy development of further high performance computational systems embedding the best capabilities of the two platforms.
Forschungsteam innerhalb von HES-SO:
, Dassatti Alberto
, Auberson Olivier
Durée du projet:
01.04.2011 - 30.09.2012
Montant global du projet: 109'800 CHF
Requérant(e)s: ReDS, Sanchez Eduardo, ReDS
VD - Ra&D; European commission
Description du projet :
We will develop a scalable hardware platform made of custom reconfigurable devices endowed with bio-inspired capabilities that will enable the simulation of large-scale complex systems and the study of emergent complex behaviors in a virtually unbounded wireless network of computing modules.
At the heart of these ubiquitous computing modules (ubidules), we will use a custom reconfigurable electronic device capable of implementing bio-inspired mechanisms such as growth, learning, and evolution. This reconfigurable circuit will be associated to rich sensory elements and wireless communication capabilities. Such an infrastructure will provide several advantages compared to
classical software simulations: speed-up, an inherent real-time interaction with the environment, self-organization capabilities, simulation in the presence of uncertainty, and distributed multi-scale simulations.
The strong interaction between our hardware infrastructure and the real environment circumvent the need to simulate the environment and ease the occurrence of unexpected emergent phenomena. The observation of such emergent phenomena will be now facilitated by the shorter simulation time,
brought by the hardware speed-up.
One of the major difficulties of a complex system simulation is to define the structural organization of the modules composing the model. The self-organization and bio-inspired capabilities of our platform will bring an innovative solution to this problem: an evolving and hierarchical structure.
The function of each ubidule can be dynamically and autonomously determined by the simulation itself: it can be an independent agent or a part of a largest entity.
We have identified four domains where our modeling infrastructure will prove its usefulness as a powerful and innovative simulation tool: biologically-plausible developing neural networks modeling, culture dissemination modeling, gene- regulatory networks modeling, and cooperative collective robotics modeling. We will perform qualitative and quantitative comparisons between classical software implementations of these four target modeling applications and their implementation running on a network of ubidules, our PERPLEXUS platform.
The PERPLEXUS platform will thus provide an unprecedented modeling framework thanks to the pervasive nature of the hardware platform, its bio-inspired capabilities, its strong interaction with the environment, and its dynamical topology.
Forschungsteam innerhalb von HES-SO:
Upegui Posada Andres
, Thoma Yann
, Satizabal Mejia Hector Fabio
, Graf Yoan
, Corbaz Alexandre
, Perez Uribe Andres
, Masle Sébastien
, Auberson Olivier
Partenaires académiques: ReDS; CE-RaD; UPC; UJF; UNIL; Politechnika Lodzka; Wany Robotics; CNRS; SCIPROM; Sanchez Eduardo, ReDS
Durée du projet:
01.09.2006 - 31.03.2010
Montant global du projet: 3'578'798 CHF
Michael Philippe, Jérôme Guitton, Sylvain Goutelle, Yann Thoma, Bertrand Favier, Nour Chtiba, Mauricette Michallet, Amine Belhabri
Therapeutic Drug Monitoring,
46 (2024), 1, 127-131
Link zur Publikation
Background: Venetoclax (VNX)-based regimens have demonstrated significantly favorable outcomes in patients with acute myeloid leukemia (AML) and are now becoming the standard treatment. Tyrosine kinase inhibitors are administered at a fixed dose, irrespective of body surface area or weight. For such orally targeted therapies, real-world data have highlighted a larger pharmacokinetic (PK) interindividual variability (IIV) than expected. Even if VNX PKs have been well characterized and described in the literature, only 1 clinical trial-based PK study has been conducted in patients with AML. This study aimed to evaluate the PK of VNX in AML patients.
Material and methods: We retrospectively analyzed all patients treated with a combination of VNX-azacitidine between January and July 2022 at our center, using at least 1 available VNX blood sample. Based on a previously published population PK model, individual PK parameters were estimated to evaluate the exposure and IIV.
Results: and Discussion. Twenty patients received VNX in combination with azacitidine, according to the PK data. A total of 93 plasma concentrations were collected. The dose of VNX was 400 mg, except in 7 patients who received concomitant posaconazole (VNX 70 mg). The patients' weight ranged from 49 kg to 108 kg (mean = 78 kg). Mean individual clearance was 13.5 ± 9.4 L/h with mean individual daily area under the concentration-time curves of 35.8 mg.h/L with significant IIV (coefficient of variation = 41.1%). Ten patients were still alive (8 in complete response), but all experienced at least 1 hematological toxicity of grade ≥ 3.
Conclusions: Based on the observed large PK variability in the data from our real-world AML patients, the risk of drug interactions and the recommended fixed-dosage regimen of VNX therapeutic drug monitoring may be useful.
Sylvain Goutelle, Florent Wallet, Yann Thoma, Jean-Rémi Peclard, Laurent Bourguignon, Sabine Cohen, Eric Kipnis, Jason Roberts, Bernard Allaouchiche, Arnaud Friggeri
Anaesthesia Critical Care & Pain Medicine,
42, 6, 101286
Myriam Briki, Pascal André, Yann Thoma, Nicolas Widmer, Anna D. Wagner, Laurent A. Decosterd, Thierry Buclin, Monia Guidi, Sandro Carrara
2023, vol. 15, no. 4, article no. 1283
Therapeutic drug monitoring (TDM) of conventional cytotoxic chemotherapies is strongly supported yet poorly implemented in daily practice in hospitals. Analytical methods for the quantification of cytotoxic drugs are instead widely presented in the scientific literature, while the use of these therapeutics is expected to keep going for longer. There are two main issues hindering the implementation of TDM: turnaround time, which is incompatible with the dosage profiles of these drugs, and exposure surrogate marker, namely total area under the curve (AUC). Therefore, this perspective article aims to define the adjustment needed from current to efficient TDM practice for cytotoxics, namely point-of-care (POC) TDM. For real-time dose adjustment, which is required for chemotherapies, such POC TDM is only achievable with analytical methods that match the sensitivity and selectivity of current methods, such as chromatography, as well as model-informed precision dosing platforms to assist the oncologist with dose fine-tuning based on quantification results and targeted intervals.
Rick Wertenbroek, Ioannis Xenarios, Yann Thoma, Olivier Delaneau
2023, vol. 3, no. 1
The positional Burrows-Wheeler transform (PBWT) data structure allows for efficient haplotype data matching and compression. Its performance makes it a powerful tool for bioinformatics. However, existing algorithms do not exploit parallelism due to inner dependencies. We introduce a new method to break the dependencies and show how to fully exploit modern multi-core processors.
Asad E. Patanwala, Danijela Spremo, Yann Thoma, Willem C. Alffenaa, Sophie Stocker
Critical Care Research and Practice,
2022, article no. 7011376
Purpose. To assess the agreement in 24-hour area under the curve (AUC24) value estimates between commonly used vancomycin population pharmacokinetic models in the critically ill. Materials and Methods. Adults admitted to intensive care who received intravenous vancomycin and had a serum vancomycin concentration available were included. AUC24 values were determined using Tucuxi (revision cd7bd7a8) for dosing intervals with a vancomycin concentration using three models (Goti 2018, Colin 2019, and Thomson 2009) previously evaluated in the critically ill. AUC24 values were categorized as subtherapeutic (<400 mg·h/L), therapeutic (400–600 mg·h/L), or toxic (>600 mg·h/L), assuming a minimum inhibitory concentration of 1 mg/L. AUC24 value categorization was compared across the three models and reported as percent agreement. Results. Overall, 466 AUC24 values were estimated in 188 patients. Overall, 52%, 42%, and 47% of the AUC24 values were therapeutic for the Goti, Colin, and Thomson models, respectively. The agreement of AUC24 values between all three models was 48% (223/466), Goti-Colin 59% (193/466), Goti-Thomson 68% (318/466), and Colin-Thomson 67% (314/466). Conclusion. In critically ill patients, vancomycin AUC24 values obtained from different pharmacokinetic models are often discordant, potentially contributing to differences in dosing decisions. This highlights the importance of selecting the optimal model.
Sylvain Goutelle, Yann Thoma, Roxane Buffet, Michael Philippe, Thierry Buclin, Monia Guidi, Chantal Csajka
2022, vol. 14, article no. 2107
Busulfan, a drug used in conditioning prior to hematopoietic stem cell transplantation (HSCT) in children, has a narrow therapeutic margin. The model-informed precision dosing (MIPD) of busulfan is desirable, but there is a lack of validated tools. The objective of this study was to implement and cross-validate a population pharmacokinetic (PK) model in the Tucuxi software for busulfan MIPD in HSCT children. A search of the literature was performed to identify candidate population PK models. The goodness of fit of three selected models was assessed in a dataset of 178 children by computing the mean error (ME) and root-mean-squared error of prediction (RMSE). The best model was implemented in Tucuxi. The individual predicted concentrations, the area under the concentration-time curve (AUC), and dosage requirements were compared between the Tucuxi model and a reference model available in the BestDose software in a subset of 61 children. The model from Paci et al. best fitted the data in the full dataset. In a subset of 61 patients, the predictive performance of Tucuxi and BestDose models was comparable with ME values of 6.4% and −2.5% and RMSE values of 11.4% and 13.6%, respectively. The agreement between the estimated AUC and the predicted dose was good, with 6.6% and 4.9% of the values being out of the 95% limits of agreement, respectively. To conclude, a PK model for busulfan MIPD was cross-validated and is now available in the Tucuxi software.
Rick Wertenbroek, Simone Rubinacci, Ioannis Xanarios, Yann Thoma, Olivier Delaneau
2022, vol. 38, no. 15, pp. 3778-3784
Motivation : Generation of genotype data has been growing exponentially over the last decade. With the large size of recent datasets comes a storage and computational burden with ever increasing costs. To reduce this burden, we propose XSI, a file format with reduced storage footprint that also allows computation on the compressed data and we show how this can improve future analyses.
Results : We show that xSqueezeIt (XSI) allows for a file size reduction of 4−20× compared with compressed BCF and demonstrate its potential for ‘compressive genomics’ on the UK Biobank whole-genome sequencing genotypes with 8× faster loading times, 5× faster run of homozygozity computation, 30× faster dot products computation and 280× faster allele counts.
Availability and implementation : The XSI file format specifications, API and command line tool are released under open-source (MIT) license and are available at https://github.com/rwk-unil/xSqueezeIt .
Supplementary information : Supplementary data are available at Bioinformatics online.
Véronique Suttels, Pascal André, Yann Thoma, François Veuve, Laurent Decosterd, Benoît Guery, Thierry Buclin
2022, vol. 4, no. 2, article no. dlac043
To describe the therapeutic drug monitoring (TDM) of cefepime in non-critically ill adults and compare four different ways of dosing: conventional table-based; empirically adjusted following TDM; individualized based on a population pharmacokinetic (PopPK) model without TDM; and TDM-adjusted with a Bayesian approach integrating TDM and PopPK. We conducted a retrospective study in a tertiary centre to examine the current practice of TDM and to evaluate the potential for improvement by PopPK-based software individualization. The prediction of trough concentrations and the total daily doses (TDD) prescribed according to each approach were compared by calculating the mean logarithmic bias and the root mean squared error, complemented by linear regression and variance analysis. Among 168 trough concentrations in 119 patients (median: 12 mg/L), 38.6% of measurements exceeded 15 mg/L, the reported threshold for neurotoxicity. Nine patients developed neurotoxicity. The prediction performance of PopPK alone for trough concentrations was moderate, but clearly improved after integration of TDM. Accordingly, TDD were significantly lower for a priori PopPK-based dosage (mean: 2907 mg/24 h) compared with actual table-based dosage (4625 mg/24 h, P < 0.001). They were also lower for a posteriori dosage based on PopPK and TDM (3377 mg/24 h) compared with actual dosage after empirical TDM (4233 mg/24 h, P < 0.001), as model-based adjustment privileged more frequent administrations. Our observations support routine TDM of cefepime to prevent overdosing and subsequent toxicity in the non-critically ill. Software-based individualization seems promising to optimize the benefits of TDM, but has little potential to replace it.
Justine Heitzmann, Yann Thoma, Romain Bricca, Marie-Claude Gagnieu, Vincent Leclerc, Sandrine Roux, Anne Conrad, Tristan Ferrry, Sylvain Goutelle
2022, vol. 14, no. 1, article no. 114
Daptomycin is a candidate for therapeutic drug monitoring (TDM). The objectives of this work were to implement and compare two pharmacometric tools for daptomycin TDM and precision dosing. A nonparametric population PK model developed from patients with bone and joint infection was implemented into the BestDose software. A published parametric model was imported into Tucuxi. We compared the performance of the two models in a validation dataset based on mean error (ME) and mean absolute percent error (MAPE) of individual predictions, estimated exposure and predicted doses necessary to achieve daptomycin efficacy and safety PK/PD targets. The BestDose model described the data very well in the learning dataset. In the validation dataset (94 patients, 264 concentrations), 21.3% of patients were underexposed (AUC24h < 666 mg.h/L) and 31.9% of patients were overexposed (Cmin > 24.3 mg/L) on the first TDM occasion. The BestDose model performed slightly better than the model in Tucuxi (ME = −0.13 ± 5.16 vs. −1.90 ± 6.99 mg/L, p < 0.001), but overall results were in agreement between the two models. A significant proportion of patients exhibited underexposure or overexposure to daptomycin after the initial dosage, which supports TDM. The two models may be useful for model-informed precision dosing.
Sujita W. Narayan, Yann Thoma, Philip G. Drennan, Hannah Yejin Kim, Jan-Willem Alffenaar, Sebastiaan Van Hal, Asad E. Patanwala
Critical Care Medicine,
Objectives : It is recommended that therapeutic monitoring of vancomycin should be guided by 24-hour area under the curve concentration. This can be done via Bayesian models in dose-optimization software. However, before these models can be incorporated into clinical practice in the critically ill, their predictive performance needs to be evaluated. This study assesses the predictive performance of Bayesian models for vancomycin in the critically ill. Design: Retrospective cohort study. Setting: Single-center ICU. Patients: Data were obtained for all patients in the ICU between 1 January, and 31 May 2020, who received IV vancomycin. The predictive performance of three Bayesian models were evaluated based on their availability in commercially available software. Predictive performance was assessed via bias and precision. Bias was measured as the mean difference between observed and predicted vancomycin concentrations. Precision was measured as the sd of bias, root mean square error, and 95% limits of agreement based on Bland-Altman plots. Interventions: None. Measurements and main results: A total of 466 concentrations from 188 patients were used to evaluate the three models. All models showed low bias (-1.7 to 1.8 mg/L), which was lower with a posteriori estimate (-0.7 to 1.8 mg/L). However, all three models showed low precision in terms of sd (4.7-8.8 mg/L) and root mean square error (4.8-8.9 mg/L). The models underpredicted at higher observed vancomycin concentrations (bias 0.7-3.2 mg/L for < 20 mg/L; -5.1 to -2.3 for ≥ 20 mg/L) and the Bland-Altman plots showed a great deviation between observed and predicted concentrations. Conclusions: Bayesian models of vancomycin show not only low bias, but also low precision in the critically ill. Thus, Bayesian-guided dosing of vancomycin in this population should be used cautiously.
Rick Wertenbroek, Yann Thoma, Flavio Maurizio Mor, Sara Grassi, Marc Olivier Heuschkel, Adrien Roux, Luc Stoppini
IEEE Transactions on Biomedical Circuits and Systems,
2021, vol. 15, no, 4, pp. 743 - 755
In this paper we present SpikeOnChip, a custom embedded platform for neuronal activity recording and online analysis. The SpikeOnChip platform was developed in the context of automated drug testing and toxicology assessments on neural tissue made from human induced pluripotent stem cells. The system was developed with the following goals: to be small, autonomous and low power, to handle micro-electrode arrays with up to 256 electrodes, to reduce the amount of data generated from the recording, to be able to do computation during acquisition, and to be customizable. This led to the choice of a Field Programmable Gate Array System-On-Chip platform. This paper focuses on the embedded system for acquisition and processing with key features being the ability to record electrophysiological signals from multiple electrodes, detect biological activity on all channels online for recording, and do frequency domain spectral energy analysis online on all channels during acquisition. Development methodologies are also presented. The platform is finally illustrated in a concrete experiment with bicuculline being administered to grown human neuronal tissue through microfluidics, resulting in measurable effects in the spike recordings and activity. The presented platform provides a valuable new experimental instrument that can be further extended thanks to the programmable hardware and software.
Philip G. Drennan, Yann Thoma, Lucinda Barry, Joahn Matthey, Sheila Sivam, Sebastiaan J. van Hal
Therapeutic Drug Monitoring,
2021, vol. 43, no. 4, pp. 505-511
Background: Intravenous tobramycin treatment requires therapeutic drug monitoring (TDM) to ensure safety and efficacy when used for prolonged treatment, as in infective exacerbations of cystic fibrosis. The 24-hour area under the concentration-time curve (AUC24) is widely used to guide dosing; however, there remains variability in practice around methods for its estimation. The objective of this study was to determine the potential for a sparse-sampling strategy using a single postinfusion tobramycin concentration and Bayesian forecasting to assess the AUC24 in routine practice.
Methods: Adults with cystic fibrosis receiving once-daily tobramycin had paired concentrations measured 2 hours (c1) and 6 hours (c2) after the end of infusion as routine monitoring. AUC24 exposures were estimated using Tucuxi, a Bayesian forecasting application that incorporates a validated population pharmacokinetic model. Simulations were performed to estimate AUC24 using the full data set using c1 and c2, compared with estimates using depleted data sets (c1 or c2 only), with and without concentration data from earlier in the course. The agreement between each simulation condition and the reference was assessed graphically and numerically using the median difference (∆) AUC24 and (relative) root mean square error (rRMSE) as measures of bias and accuracy, respectively.
Results: A total of 55 patients contributed 512 concentrations from 95 tobramycin courses and 256 TDM episodes. Single concentration methods performed well, with median ∆AUC24 <2 mg·h·L-1 and rRMSE of <15% for sequential c1 and c2 conditions.
Conclusions: Bayesian forecasting implemented in Tucuxi, using single postinfusion concentrations taken 2-6 hours after tobramycin administration, yield similar exposure estimates to more intensive (two-sample) methods and are suitable for routine TDM practice.
Thierry Buclin, Yann Thoma, Nicolas Widmer, Pascal André, Monia Guidi, Chantal Csajka, Laurent A. Decosterd
Frontiers in Pharmacology,
2020, vol. 11, no. 177
Pharmacometric methods have hugely benefited from progress in analytical and computer sciences during the past decades, and play nowadays a central role in the clinical development of new medicinal drugs. It is time that these methods translate into patient care through therapeutic drug monitoring (TDM), due to become a mainstay of precision medicine no less than genomic approaches to control variability in drug response and improve the efficacy and safety of treatments. In this review, we make the case for structuring TDM development along five generic questions: 1) Is the concerned drug a candidate to TDM? 2) What is the normal range for the drug's concentration? 3) What is the therapeutic target for the drug's concentration? 4) How to adjust the dosage of the drug to drive concentrations close to target? 5) Does evidence support the usefulness of TDM for this drug? We exemplify this approach through an overview of our development of the TDM of imatinib, the very first targeted anticancer agent. We express our position that a similar story shall apply to other drugs in this class, as well as to a wide range of treatments critical for the control of various life-threatening conditions. Despite hurdles that still jeopardize progress in TDM, there is no doubt that upcoming technological advances will shape and foster many innovative therapeutic monitoring methods.
Yann Thoma, Alberto Dassatti, Daniel Molla, Enrico Petraglio
Microprocessors and Microsystems,
205, vol. 39, no. 7, pp. 565-575
In recent years two main platforms emerged as powerful key players in the domain of parallel computing: GPUs and FPGAs. Many researches investigate interaction and benefits of coupling them with a general purpose processor (CPU), but very few, and only very recently, integrate the two in the same computational system. Even less researches are focusing on direct interaction of the two platforms.
This paper presents an implementation of a GPU-FPGA direct communication. The transfer is triggered by a central CPU but managed by the FPGA, in a DMA-like manner. An initial framework has been developed on a Virtex-5 FPGA, with a PCIe Gen1.1×1 setup, and demonstrates a 200 MB/s data rate. A new implementation on Virtex-7 has been conducted, supporting Gen3.0×8, with a demonstrated throughput of up to 2.4 GB/s in a Gen2.1×8 setup. Performance results between different hardware setups are therefore presented and compared. The various measurements demonstrate achieved data rates that are close to the theoretical maximum, with some interesting outliners, and a very low interfacing latency.
Yasser Baleghi Damavandi, Karim Mohammadi, Andres Upegui Posada, Yann Thoma
International Journal of Engineering,
2014, vol 27, no. 1, pp. 101-112
A permanent physical fault in communication lines usually leads to a failure. The feasibility of evolution of a self-organized communication is studied in this paper to mitigate this problem. In this case a communication protocol may emerge between blocks and also can adapt itself to environmental changes like physical faults and defects. In spite of the faults, blocks may continue to function, since a self-organized nature can provide self-healing capabilities. In the present paper, Evolvable Hardware is to create such a fault tolerant communication without any predefined protocol using a GA algorithm. Evolvable Hardware is a concept that aims the application of evolutionary algorithms to hardware design. The feasibility of this idea is studied in simulation of two reconfigurable blocks that are intended to transmit video streams through their communication lines. Permanent physical faults are induced in the communication lines between Evolvable Hardware blocks. Although the results show the emergence of fault tolerant protocols among Evolvable Hardware blocks without human intervention, there are some limitations in functional and gate level evolution of the blocks. Thus, a new adaptive approach is presented in this paper to defeat some limitations like the stalling effect of GA in faulty conditions.
Aline Fuchs, Chantal Csajka, Yann Thoma, Thierry Buclin, Nicolas Widmer
2013, vol. 52, no. 1, pp. 9-22
Therapeutic drug monitoring (TDM) aims to optimize treatments by individualizing dosage regimens based on the measurement of blood concentrations. Dosage individualization to maintain concentrations within a target range requires pharmacokinetic and clinical capabilities. Bayesian calculations currently represent the gold standard TDM approach but require computation assistance. In recent decades computer programs have been developed to assist clinicians in this assignment. The aim of this survey was to assess and compare computer tools designed to support TDM clinical activities. The literature and the Internet were searched to identify software. All programs were tested on personal computers. Each program was scored against a standardized grid covering pharmacokinetic relevance, user friendliness, computing aspects, interfacing and storage. A weighting factor was applied to each criterion of the grid to account for its relative importance. To assess the robustness of the software, six representative clinical vignettes were processed through each of them. Altogether, 12 software tools were identified, tested and ranked, representing a comprehensive review of the available software. Numbers of drugs handled by the software vary widely (from two to 180), and eight programs offer users the possibility of adding new drug models based on population pharmacokinetic analyses. Bayesian computation to predict dosage adaptation from blood concentration (a posteriori adjustment) is performed by ten tools, while nine are also able to propose a priori dosage regimens, based only on individual patient covariates such as age, sex and bodyweight. Among those applying Bayesian calculation, MM-USC*PACK© uses the non-parametric approach. The top two programs emerging from this benchmark were MwPharm© and TCIWorks. Most other programs evaluated had good potential while being less sophisticated or less user friendly. Programs vary in complexity and might not fit all healthcare settings. Each software tool must therefore be regarded with respect to the individual needs of hospitals or clinicians. Programs should be easy and fast for routine activities, including for non-experienced users. Computer-assisted TDM is gaining growing interest and should further improve, especially in terms of information system interfacing, user friendliness, data storage capability and report generation.
Damien Stucki, Claudio Barreiro, Sylvain Fasel, Jean-Daniel Gautier, Olivier Gay, Nicolas Gisin, Rob Thew, Yann Thoma, Patrick Trinkler, Fabien Vannel, Hugo Zbinden
2009, vol. 17, no. 16, pp. 13326-13334
Quantum key distribution (QKD) is the first commercial quantum technology operating at the level of single quanta and is a leading light for quantum-enabled photonic technologies. However, controlling these quantum optical systems in real world environments presents significant challenges. For the first time, we have brought together three key concepts for future QKD systems: a simple high-speed protocol; high performance detection; and integration both, at the component level and for standard fibre network connectivity. The QKD system is capable of continuous and autonomous operation, generating secret keys in real time. Laboratory and field tests were performed and comparisons made with robust InGaAs avalanche photodiodes and superconducting detectors. We report the first real world implementation of a fully functional QKD system over a 43dB-loss (150km) transmission line in the Swisscom fibre optic network where we obtained average real-time distribution rates over 3 hours of 2.5bps.
M. Peev, C. Pacher, R. Alléaume, C. Barreiro, J. Bouda, Yann Thoma
New journal of physics,
2009, vol. 11, no. 075001
In this paper, we present the quantum key distribution (QKD) network designed and implemented by the European project SEcure COmmunication based on Quantum Cryptography (SECOQC) (2004–2008), unifying the efforts of 41 research and industrial organizations. The paper summarizes the SECOQC approach to QKD networks with a focus on the trusted repeater paradigm. It discusses the architecture and functionality of the SECOQC trusted repeater prototype, which has been put into operation in Vienna in 2008 and publicly demonstrated in the framework of a SECOQC QKD conference held from October 8 to 10, 2008. The demonstration involved one-time pad encrypted telephone communication, a secure (AES encryption protected) video-conference with all deployed nodes and a number of rerouting experiments, highlighting basic mechanisms of the SECOQC network functionality.
The paper gives an overview of the eight point-to-point network links in the prototype and their underlying technology: three plug and play systems by id Quantique, a one way weak pulse system from Toshiba Research in the UK, a coherent one-way system by GAP Optique with the participation of id Quantique and the AIT Austrian Institute of Technology (formerly ARCAustrian Research Centers GmbH—ARC is now operating under the new name AIT Austrian Institute of Technology GmbH following a restructuring initiative.), an entangled photons system by the University of Vienna and the AIT, a continuous-variables system by Centre National de la Recherche Scientifique (CNRS) and THALES Research and Technology with the participation of Université Libre de Bruxelles, and a free space link by the Ludwig Maximillians University in Munich connecting two nodes situated in adjacent buildings (line of sight 80 m). The average link length is between 20 and 30 km, the longest link being 83 km. The paper presents the architecture and functionality of the principal networking agent—the SECOQC node module, which enables the authentic classical communication required for key distillation, manages the generated key material, determines a communication path between any destinations in the network, and realizes end-to-end secure transport of key material between these destinations. The paper also illustrates the operation of the network in a number of typical exploitation regimes and gives an initial estimate of the network transmission capacity, defined as the maximum amount of key that can be exchanged, or alternatively the amount of information that can be transmitted with information theoretic security, between two arbitrary nodes.
Andres Upegui, Yann Thoma, Eduardo Sanchez, Andres Perez-Uribe, Juan Manuel Moreno, Jordi Madrenas, Gilles Sassatelli
International Journal of Knowledge-based and Intelligent Engineering Systems,
2008, vol. 12, no. 3, pp- 201-212
This paper introduces the Perplexus hardware platform, a scalable computing substrate made of custom reconfigurable devices endowed with bio-inspired capabilities. This platform will enable the simulation of large-scale complex systems and the study of emergent complex behaviors in a virtually unbounded wireless network of computing modules. The modularity and flexibility of the platform are the key for tackling the diverse hardware setup needs of the different applications, mainly in the form of a pervasive distributed computing platform and a bio-inspired chip architecture. The Perplexus platform will provide a novel modeling framework thanks to the pervasive nature of the hardware platform, its bio-inspired capabilities, its strong interaction with the environment, and its dynamic topology. The final infrastructure will be used as a simulation tool for three applications: neurobiological modeling, culture dissemination modeling, and cooperative collective robotics.
Andres Upegui, Yann Thoma, Andres Perez-Uribe, Eduardo Sanchez
Proceedings of NASA/ESA Conference on Adaptive Hardware and Systems, 22-25 June 2008, Noorwijk, Netherlands,
The ubichip is a bio-inspired reconfigurable circuit developed in the framework of the european project Perplexus. The ubichip offers special reconfigurability capabilities, being the dynamic routing one of them. This paper describes how to exploit the dynamic routing capabilities of the ubichip in order to implement synaptogenetic neural networks. We present two techniques for dynamically generating the network topology, we describe their implementation in the ubichip, and we analyse the resulting topology. This work constitutes a first step toward neural circuits exhibiting more realistic neural plasticity features.
Will Barker, David M. Halliday, Yann Thoma, Eduardo Sanchez, Gianluca Tempesti, Andy M. Tyrrell
IEEE Transactions on Evolutionary Computation,
2007, vol. 11, no. 5, pp. 666-684
Fault tolerance is a crucial operational aspect of biological systems and the self-repair capabilities of complex organisms far exceeds that of even the most advanced electronic devices. While many of the processes used by nature to achieve fault tolerance cannot easily be applied to silicon-based systems, in this paper we show that mechanisms loosely inspired by the operation of multicellular organisms can be transported to electronic systems to provide self-repair capabilities. Features such as dynamic routing, reconfiguration, and on-chip reprogramming can be invaluable for the realization of adaptive hardware systems and for the design of highly complex systems based on the kind of unreliable components that are likely to be introduced in the not-too-distant future. In this paper, we describe the implementation of fault tolerant features that address error detection and recovery through dynamic routing, reconfiguration, and on-chip reprogramming in a novel application specific integrated circuit. We take inspiration from three biological models: phylogenesis, ontogenesis, and epigenesis (hence the POE in POEtic). As in nature, our approach is based on a set of separate and complementary techniques that exploit the novel mechanisms provided by our device in the particular context of fault tolerance.
J. Manuel Moreno, Yann Thoma, Eduardo Sanchez, Jan Eriksson, Javier Iglesias, Alessandro Villa
2006, vol.3, no. 1-3, pp. 32-47
One of the major obstacles found when trying to construct artefacts derived from principles observed in living beings is the lack of actual dynamic hardware with autonomous capabilities. Even if programmable devices offer the possibility of modifying the functionality implemented in the device, they rely on external hardware and software elements to provide its physical configuration. In this paper we present a new family of electronic devices, called POEtic, whose architecture has been derived from the basic properties that can be extracted from the three major organization principles present in living beings: phylogenesis, ontogenesis and epigenesis. We will demonstrate that the capabilities present in these new programmable devices make them an ideal candidate for the real-time emulation of large-scale biologically inspired spiking neural network models.
Yann Thoma, Gianluca Tempesti, Eduardo Sanchez, Juan-Manuel Moreno Arostegui
2004, vol. 76, no. 1–3, pp. 191-200
In this paper, we introduce the general architecture of a new electronic tissue called POEtic. This reconfigurable circuit is designed to ease the implementation of bio-inspired systems that bring cellular applications into play. It contains special features that allow a developer to realize systems that require evolution (Phylogenesis), development (Ontogenesis), and/or learning (Epigenesis). A dynamic routing algorithm has been added to a structure similar to that of common commercial FPGAs, in order to allow the creation of data paths between cells. As the creation of these paths is dynamic, it is possible to add new cells or to repair faulty ones at runtime.
Rick Wertenbroek, Yann Thoma
Proceedings of 2018 NASA/ESA Conference on Adaptive Hardware and Systems (AHS), 6-9 August 2018, Edinburgh, UK
Link zur Konferenz
k-mer counting is an essential algorithm found in many genomic related processes. It may seem like a rather trivial task but is in fact computationally expensive due to the sheer amount of data. The ever growing rate at which data is generated in genomics requires the creation of novel solutions leveraging new technologies to keep up the pace. In this paper we explore the use of in-memory operations of Hybrid Memory Cubes (HMC) to accelerate k-mer counting. The resulting accelerator is compared to an existing accelerator also using HMC memory, as well as state of the art k-mer counting software. The use of in-memory operations resulted in a 14.6% to 16.9% performance improvement over using the HMC without them. The accelerator showed a speed-up of 3-4x over software when running with a single FPGA and HMC and a speed-up of 16-17x when using 4 FPGAs and 4 HMCs.
Alevtina Dubovistkaya, Thierry Buclin, Michael Schumacher, Karl Aberer, Switzerland Lausanne, Yann Thoma, Switzerland Yverdon-les-Bains
Proceedings of the 8th ACM International Conference on Bioinformatics, Computational Biology and Health Informatics
Therapeutic Drug Monitoring (TDM) is a key concept in precision medicine. The goal of TDM is to avoid therapeutic failure or toxic effects of a drug due to insufficient or excessive circulating concen-tration exposure related to between-patient variability in the drug’s disposition. We present TUCUXI – an intelligent system for TDM. By making use of embedded mathematical models, the software allows to compute maximum likelihood individual predictions of drug concentrations from population pharmacokinetic data, based on patient’s parameters and previously observed concentrations. TUCUXI was developed to be used in medical practice, to assist clinicians in taking dosage adjustment decisions for optimizing drug concentration levels. This software is currently being tested in a University Hospital. In this paper we focus on the process of software integration in clinical workflow. The modular architec-ture of the software allows us to plug in a module enabling data aggregation for research purposes. This is an important feature in order to develop new mathematical models for drugs, and thus to improve TDM. Finally we discuss ethical issues related to the use of an automated decision support system in clinical practice, in particular if it allows data aggregation for research purposes.
Alevtina Dubovitskaya, Thierry Buclin, Michael Schumacher, Karl Aberer, Yann Thoma
Proceedings of the 8th ACM International Conference on Bioinformatics, Computational Biology, and Health Informatics, 20-23 August 2017, Boston, Massachusetts, USA
Therapeutic Drug Monitoring (TDM) is a key concept in precision medicine. The goal of TDM is to avoid therapeutic failure or toxic effects of a drug due to insufficient or excessive circulating concen-tration exposure related to between-patient variability in the drug’s disposition. We present TUCUXI – an intelligent system for TDM. By making use of embedded mathematical models, the software allows to compute maximum likelihood individual predictions of drug concentrations from population pharmacokinetic data, based on patient’s parameters and previously observed concentrations. TUCUXI was developed to be used in medical practice, to assist clinicians in taking dosage adjustment decisions for optimizing drug concentration levels. This software is currently being tested in a University Hospital. In this paper we focus on the process of software integration in clinical work ow. The modular architecture of the software allows us to plug in a module enabling data aggregation for research purposes. This is an important feature in order to develop new mathematical models for drugs, and thus to improve TDM. Finally we discuss ethical issues related to the use of an automated decision support system in clinical practice, in particular if it allows data aggregation for research purposes.
Rick Wertenbroek, Enrico Petraglio, Yann Thoma
Lecture Notes in Computer Science ; Proceedings of 17th International Conference on Algorithms and Architectures for Parallel Processing, ICA3PP 2017, 21-23 August 2017, Helsinki, Finland
High throughput DNA sequencing made individual genome profiling possible and produces very large amounts of data. Today data and associated metadata are stored in FASTQ text file assemblies carrying the information of genome fragments called reads. Current techniques rely on mapping these reads to a common reference genome for compression and analysis. However, about 10% of the reads do not map to any known reference making them difficult to compress or process. These reads are of high importance because they hold information absent from any reference. Finding overlaps in these reads can help subsequent processing and compression tasks tremendously. Within this context clustering is used to find overlapping unmapped reads and sort them in groups. Clustering being an extremely time consuming task a modular multi-FPGA pipeline was designed and is the focus of this paper. A pipeline with 6 FPGAs was created and has shown a speed-up of ×5 compared to existing FPGA implementations. Resulting enriched files encoding reads and clustering results show file sizes within a 10% margin of the best DNA compressors while providing valuable extra information.
Enrico Petraglio, Rick Wertenbroek, Flavio Capitao, Nicolas Guex, Christian Iseli, Yann Thoma
Lecture Notes in Computer Science ; Proceedings of Applied reconfigurable computing, 13th International Symposium, ARC 2017, 3-7 April 2017, Delft, The Netherlands
Current sequencing machine technology generates very large and redundant volumes of genomic data for each biological sample. Today data and associated metadata are formatted in very large text file assemblies called FASTQ carrying the information of billions of genome fragments referred to as “reads” and composed of strings of nucleotide bases with lengths in the range of a few tenths to a few hundreds bases. Compressing such data is definitely required in order to manage the sheer amount of data soon to be generated. Doing so implies finding redundant information in the raw sequences. While most of it can be mapped onto the human reference genome and fits well for compression, about 10% of it usually does not map to any reference . For these orphan sequences, finding redundancy will help compression. Doing so requires clustering these reads, a very time consuming process. Within this context this paper presents a FPGA implementation of a clustering algorithm for genomic reads, implemented on Pico Computing EX-700 AC-510 hard-ware, offering more than a 1000×speed up over a CPU implementation while reducing power consumption by a 700 factor.
Alena Simalastar, Romain Bornet, Wenqi You, Yann Thoma
Proceedings of 2014 IEEE International Conference on Bioinformatics and Bioengineering, 10-12 November 2014, Boca Raton, FL, USA
Alberto Dassatti, Olivier Auberson, Romain Bornet, Etienne Messerli, Jérôme Stadelmann, Yann Thoma
Proceedings of 2014 6th European Embedded Design in Education and Research Conference (EDERC), 11-12 September 2014, Milano, Italy
Embedded systems are shaping a new world. There is no sector immune to their adoption and the effects in the long term are unpredictable and fascinating. Embedded systems are designed by embedded system engineers. What technical education and what kind of practical skills these new engineers will need? This is a complex and unanswered question. In this paper we describe our proposal to equip engineering students with knowledge and experience: REPTAR. REPTAR (Reconfigurable Embedded Platform for Training And Research) is a feature rich complex embedded system designed for giving the opportunity to tomorrow's engineers of having hands-on experience on modern technologies and learning by doing. As a side effect REPTAR revealed itself as an invaluable tool for rapid prototyping and research explorations.
Alevtina Dubovitskaya, Visara Urovi, Michael Schumacher, Matteo Vasirani, Karl Aberer, Aline Fuchsc, Thierry Buclin, Yann Thoma
Swiss Medical Informatics (SMI) Conference Swiss eHealth Summit 2014
The treatment of certain diseases such as cancer, HIV, or other serious medical conditions relies on a regular administration of critical drugs that are necessary to keep those life-threatening diseases under control. Those drugs (e.g. Efavirenz, Imatinib, Tacrolimus, Tobramycin) have a narrow therapeutic range and a poorly predictable relationship between the dose and the blood drug concentration, which may vary greatly among individuals. Therapeutic Drug Monitoring (TDM) aims at improving patient care by monitoring drug levels in the blood to individually adjust the dosage for targeting drug concentration in the therapeutic interval. In order to ensure a better prediction of the relationship between dose and drug concentration, the ISyPeM2 project (a continuation of the Nano-Tera project: Intelligent Integrated Systems for Personalized Medicine, ISyPeM, http://www.nano-era.ch/projects/368.php) has developed a Bayesian TDM approach [GWM+12] based on studies in general or special populations. This approach requires population health data (covariates, dosages, drug concentrations) to be collected and analysed by researchers, in order to enhance the prediction models. Therefore the following question arises: how is it possible to share and aggregate medical data for research purposes while preserving the patients’ privacy?
Yann Thoma, Alberto Dassatti, Daniel Molla
Proceedings of the 2013 International Conference on Reconfigurable Computing and FPGAs (ReConFig), 9-11 December 2013, Cancun, Mexico
Yann Thoma, Etienne Messerli, Michel Starkier, Daniel Molla, Sébastien Masle, Christophe Bianchi, Oliver Gubler, Claude Magliocco, Philippe Crausaz, Samuel Tâche, Denis Prêtre, Gregory Trolliet
Proceedings of 2012 NASA/ESA Conference on Adaptive Hardware and Systems (AHS), 25-28 June 2012, Erlangen, Germany
Math2Mat aims at automatically generating a VHDL description of a mathematical description written in Octave/Matlab. The generation creates a synthesizable RTL description using floating point operators (32 or 64 bits) combined in a fully pipelined way. Emphasis is put on the throughput attainable by the design, especially in the ”for loop” implementation. The software also offers a graphical user interface, letting the developer manage the different parameters before generation. Verification can also be launched from the software, a SystemVerilog testbench being automatically generated.
Yann Thoma, Andres Upegui, Andres Perez-Uribe, Eduardo Sanchez
Proceedings of 20th International conference on architecture of computing systems 2007 (ARCS 07), 15 March 2007, Zurich, Switzerland
Ontogenetic hardware, along with epigenetic (neural) hardware and phylogenetic (evolvable) hardware, are the key representatives of a new hardware conception paradigm known as bio-inspired hardware. Ontogenesis is the process that allows living beings to develop by means of mechanisms as growing, self-replication, and self-repair. During the last few years, such ontogenetic mechanisms have been presented as a solution for the design of complex electronic circuits, with the goal of coping with the increasing complexity envisioned for future nano-technology devices. This paper presents an ontogenetic mechanism that allows a system, implemented in a reconfigurable device, to self-replicate, generating an identical copy of itself, by partially self-reconfiguring the device containing it in a dynamic way.
Olivier Brousse, Gil Sassatelli, Michel Robert, François Grize, Eduardo Sanchez, Andrés Upegui, Yann Thoma
Proceedings of ICES 2010 9th international conference on Evolvable systems: from biology to hardware, 6-8 September 2010, York, UK
This paper presents a flexible agent-oriented programming framework that provides native support for bio-inspired mechanisms. This solution, developed within the Perplexus IST European project [IST-034632]1 aims at providing a means for the specification of applications running on a distributed and pervasive network of mobile nodes. In such applications, the deployed systems may face time-changing environments and bio-inspiration may prove useful bringing self-adaptability to the system. The presented framework features are demonstrated on a proof-of-concept application made of simple robots that autonomously improve their behaviour over time.
Andres Upegui, Yann Thoma, Héctor F. Satizábal, Francesco Mondada, Philippe Rétornaz, Yoan Graf, Andres Perez-Uribe, Eduardo Sanchez
This paper presents the final hardware platform developed in the Perplexus project. This platform is composed of a reconfigurable device called the ubichip, which is embedded on a pervasive platform called the ubidule, and can also be integrated on the marXbot robotic platform. The whole platform is intended to provide a hardware platform for the simulation of complex systems, and some examples of them are presented at the end of the paper.
Olivier Jorand, Andres Perez-Uribe, Henri Volken, Andres Upegui, Yann Thoma, Eduardo Sanchez, Francesco Mondada, Philippe Retornaz
Proceedings of the 2nd Symposium on Computing and Philosophy, 6-9 April 2009, Edinburgh, Scotland
There is a growing interest in attempting to study cognitive and social phenomena under the umbrella of "complex theory". We are indeed immersed in so-called "complex systems", but we are still a long way from a clear understanding of the concepts and principles that underlie the "complexity thinking" . The purpose of this paper to provide a simple (and too short) conceptual framework to understand the basic ideas that allow us to think and speak of complexity in the context of PERPLEXUS as a physical substratum for the embodiment of questions related to cognition (individual and/or social) and the material realization of philosophical thought-experiments. To do so, we will notice the controversies concerning the very existence of such a thing as a "theory of complexity". We also will capture some features that can be considered as characterizations (or fingerprints) of "complexity thinking" by contrasting them with a classical Cartesian-Newtonian mode of thinking. Then, we will stress the key role of embodiment as a necessary ingredient to be incorporated in the explanatory efforts of different domains dealing with cognition, development and evolution. We will finally explain how the platform PERPLEXUS can represent such an ideal locus for reformatting and tackling conceptual and philosophical questions grounded in aspects of complexity and embodiment.
Andres Upegui, Andres Perez-Uribe, Yann Thoma, Eduardo Sanchez
Lecture Notes in Computer Science ; Proceedings of International Conference on Evolvable Systems : ICES 2008: Evolvable Systems: From Biology to Hardware, 21-24 September 2008, Prague, Czech Republic
The ubichip is a bio-inspired reconfigurable circuit developed in the framework of the european project Perplexus. The ubichip offers special reconfigurability capabilities as self-replication and dynamic routing. This paper describes how to exploit the dynamic routing capabilities of the ubichip in order to implement plastic neural networks. We present an approach for dynamically generating a network topology, where synapses among neurons can be created or destroyed depending on the input stimuli. We describe their implementation in the ubichip, and we analyse the resulting network topology and the network development. This work constitutes a first step toward plastic neural circuits exhibiting more realistic biological features.
Olivier Brousse, Gilles Sassatelli, Y. Guillemenet, Michel Robert, François Grize, Eduardo Sanchez, Yann Thoma, Andrés Upegui, J.M. Moreno, J. Madrenas
Proceedings of Second international conference on genetic and evolutionary computing, WGEC 2008, 25-26 September 2008, Jingzhou, Hubei, China
In this paper we introduce the Bio-inspired Agent Framework (BAF) developed within the Perplexus IST European project1. This BAF is FIPA (Foundation for Intelligent and Physical Agents) compliant as based on the JADE Multi-Agent Platform, portable and suitable for Adhoc networks of mobile nodes (MANET). Its bio-inspired capabilities and reliability services provide a powerful bioinspired distributed tool that opens interesting perspectives for adaptive sensor networks.
Yann Thoma, Andres Upegui
Proceedings of the 2008 NASA/ESA conference on adaptive hardware and systems, 22-25 June 2008, Noordwijk, Netherlands
This paper introduces the UbiManager, a tool for managing the ubichip reconfigurable circuit. The ubichip is a custom reconfigurable electronic device for implementing circuits featuring bio-inspired mechanisms like growth, learning, and evolution. The ubichip has been developed in the framework of Perplexus, a European project that aims to develop a scalable hardware platform made of bio-inspired custom reconfigurable devices for simulating large-scale complex systems. In this paper, we present the software tool used for designing, simulating, emulating, debugging, configuring, and monitoring the systems to be implemented in the ubichip. This paper also presents the dissemination plans of the UbiManager, that consist in a web platform allowing researchers to access the hardware platform from any remote base station.
Eduardo Sanchez, Andres Perez-Uribe, Andrés Upegui, Yann Thoma, Juan Manuel Moreno, Andrezj Napieralski, Allessandro Villa, Gilles Sassatelli, Henri Volken, Erwan Lavarec
Proceedings of Second NASA/ESA Conference on Adaptive Hardware and Systems (AHS 2007), 5-8 August 2007, Edinburgh, UK
This paper introduces Perplexus, a European project that aims to develop a scalable hardware platform made of custom reconfigurable devices endowed with bio-inspired capabilities. This platform will enable the simulation of large-scale complex systems and the study of emergent complex behaviors in a virtually unbounded wireless network of computing modules. The final infrastructure will be used as a simulation tool for three applications: neurobiological modeling, culture dissemination modeling, and cooperative collective robotics. The Perplexus platform will provide a novel modeling framework thanks to the pervasive nature of the hardware platform, its bio-inspired capabilities, its strong interaction with the environment, and its dynamic topology.
Andres Upegui, Yann Thoma, Eduardo Sanchez, Andres Perez-Uribe, Juan Manuel Moreno, Jordi Madrenas
Proceedings of Second NASA/ESA Conference on Adaptive Hardware and Systems(AHS 2007), 5-8 August 2007, Edinburgh, UK
This paper introduces the ubichip, a custom reconfigurable electronic device capable of implementing bioinspired circuits featuring growth, learning, and evolution. The ubichip is developed in the framework of Perplexus, a European project that aims to develop a scalable hardware platform made of bio-inspired custom reconfigurable devices for simulating large-scale complex systems. In this paper, we describe the configurability and architectural mechanisms that will allow the implementation of evolvable and developmental cellular and neural systems in an efficient way. These mechanisms are dynamic routing, selfreconfiguration, and a neural-friendly logic cell’s architecture.
Damien Stucki, Sylvain Fasel, Nicolas Gisin, Yann Thoma, Hugo Zbinden
Photon Counting Applications, Quantum Optics, and Quantum Cryptography
Quantum Key Distribution (QKD) consists in the exchange of a secrete key between two distant points . Even if quantum key distribution systems exist and commercial systems are reaching the market , there are still improvements to be made: simplify the construction of the system; increase the secret key rate. To this end, we present a new protocol for QKD tailored to work with weak coherent pulses and at high bit rates . The advantages of this system are that the setup is experimentally simple and it is tolerant to reduced interference visibility and to photon number splitting attacks, thus resulting in a high efficiency in terms of distilled secret bits per qubit. After having successfully tested the feasibility of the system , we are currently developing a fully integrated and automated prototype within the SECOQC project . We present the latest results using the prototype. We also discuss the issue of the photon detection, which still remains the bottleneck for QKD.
Joël Rossier, Yann Thoma, Pierre-André Mudry, Gianluca Tempesti
Biologically inspired approaches to advanced information technology
This article describes an implementation of a basic multi-processor system that exhibits replication and differentiation abilities on the POEtic tissue, a programmable hardware designed for bio-inspired applications [1,2]. As for a living organism, whose existence starts with only one cell that first divides, our system begins with only one totipotent processor, able to implement any of the cells required by the final organism, which can also fully replicate itself, using the functionalities of the POEtic substrate. Then, analogously to the cells in a developing organism, our just replicated totipotent processors differentiate in order to execute their specific part of the complete organism functionality. In particular, we will present a working realization using MOVE processors whose instructions define the flow of data rather than the operations to be executed . It starts with one basic MOVE processor that first replicates itself three times; the four resulting processors then differentiate and connect together to implement a multi-processor modulus-60 counter.
J. Manuel Moreno, Yann Thoma, Eduardo Sanchez
Evolvable Systems: From Biology to Hardware: Proceedings of the ICES 2005
This paper will present the final hardware realization of a new family of programmable devices that has specifically being conceived in order to address the prototyping of bio-inspired principles. The devices are organized around a custom 32-bit RISC microprocessor and a custom FPGA. The internal architecture devised for the devices is scalable, so that it is possible to construct a physical hardware platform whose size matches the requirements of the application to be handled. To facilitate the development of applications for this hardware platform a complete set of design tools has been developed.
Yann Thoma, Eduardo Sanchez
Proceedings of the 1st International Workshop on Reconfigurable Communication-centric Systems-on-Chip 2005
Every commercially available FPGA supplies high routing capabilities. However, placement and routing are processed by a computer before being sent to the chip. This nonadaptive feature does not fit well with bio-inspired applications such as growing systems or neural networks with changing topology. Therefore we propose a new kind of routing, built in hardware and totally distributed. Unlike previous works about routing, our approach does not need a central control over the process. In this paper we present a new FPGA embedding this algorithm, as well as the basic idea of our architecture, based on a parallel implementation of Lee shortest path algorithm. We then present a second algorithm that decreases the number of possible congestions, a third that reduces the execution time, and a fourth that combines both techniques. Finally we introduce different neighborhoods and compare all these algorithms in terms of area, speed, path length and congestion.
Daniel Roggen, Yann Thoma, Eduardo Sanchez
Artificial Life IX: Proceedings of the Ninth International Conference on the Simulation and Synthesis of Living Systems
A novel multi-cellular electronic circuit capable of evolution and development is described here. The circuit is composed of identical cells whose shape and location in the system is arbitrary. Cells all contain the complete genetic description of the final system, as in living organisms. Through a mechanism of development, cells connect to each other using a fully distributed hardware routing mechanism and differentiate by expressing a corresponding part of the genetic code thereby taking a specific functionality and connectivity in the system. The configuration of the system is found by using artificial evolution and intrinsic evolution at the schematic level is possible. Applications include the approximation of boolean functions and the evolution of a controller capable of navigating a Khepera robot while avoiding obstacles. The circuit is suited for a custom chip called POEtic, which is a generic platform to implement bio-inspired applications.
J. Manuel Moreno, Yann Thoma, E. Sanchez, O. Torres, G. Tempesti
Proceedings of the 2004 NASA/DoD Conference on Evolvable Hardware
This paper presents the physical hardware realization of a novel bio-inspired architecture, called POEtic tissue. This electronic tissue provides a platform for the efficient implementation in actual hardware of evolutionary, epigenetic (learning) and ontogenetic (growth, self-repair, self-replication) mechanisms. After a brief introduction the overall organization of the tissue is presented. Then its main building blocks is reviewed. Finally, the implementation details of the first hardware prototype of the tissue, constructed in the form of an ASIC, is outlined. The implementation results demonstrate that the proposed architecture constitutes a good candidate when considering the electronic realization of bio-inspired principles.
Genetic and Evolutionary Computation ; Proceedings of the GECCO 2004
In the recent years, Xilinx devices, like the XC6200, were the preferred solutions for evolving digital systems. In this paper, we present a new System-On-Chip, the POEtic chip, an alternative for evolvable hardware. This chip has been specifically designed to ease the implementation of bio-inspired systems. It is composed of a microprocessor, and a programmable part, containing basic elements, like every standard Field Programmable Gate Array, on top of which sits a special layer implementing a dynamic routing algorithm. Online on-chip evolution can then be processed, as every configuration bit of the programmable array can be accessed by the microprocessor. This new platform can therefore replace the Xilinx XC6200, with the advantage of having a processor inside.
Yann Thoma, Eduardo Sanchez, Daniel Roggen, Carl Hetherington, Juan-Manuel Moreno
Proceedings of the 15th IEEE International Workshop on Rapid System Prototyping
In this paper we explain how the POEtic chip can be used for rapid prototyping. The POEtic chip, currently in the test phase, is a system-on-chip (SoC) containing a microprocessor and a reconfigurable array. Special features allow the dynamic creation of data paths in the reconfigurable array at runtime. It has been specially designed to ease the development of bio-inspired systems such as neural networks, but can serve as a general purpose platform, or as a prototype for hardware/software codesign. An AMBA bus allows POEtic chips to be connected to each other, or to external devices. After describing the hardware SoC, we discuss the software tools that have been created to design and test different applications. Three of these applications are described in order to demonstrate the utility of the POEtic chip's special features.
Yann Thoma, Eduardo Sanchez, Juan-Manuel Moreno Arostegui, Gianluca Tempesti
Field Programmable Logic and Application : Proceedings of the FPL 2003
In this paper we present a new dynamic routing algorithm specially implemented for a new electronic tissue called POEtic. This reconfigurable circuit is designed to ease the implementation of bio-inspired systems that bring cellular applications into play. Specifically designed for implementing cellular applications, such as neural networks, this circuit is composed of two main parts: a two-dimensional array of basic elements similar to those found in common commercial FPGAs, and a two-dimensional array of routing units that implement a dynamic routing algorithm which allows the creation of data paths between cells at runtime.
Yann Thoma, Eduardo Sanchez, Gianluca Tempesti, Juan-Manuel Moreno Arostegui
Computación reconfigurable & FPGAs : artículos seleccionados de las III Jornadas de Computación Reconñgurable y Aplicaciones
Daniel Roggen, Stéphane Hofmann, Yann Thoma, Dario Floreano
Proceedings of the NASA/DoD Conference on Evolvable Hardware 2003
A cellular hardware implementation of a spiking neural network with run-time reconfigurable connectivity is presented. It is implemented on a compact custom FPGA board, which provides a powerful reconfigurable hardware platform for hardware and software design. Complementing the system, a CPU synthesized on the FPGA takes care of interfacing the network with the external world. The FPGA board and the hardware network are demonstrated in the form of a controller embedded on the Khepera robot for a task of obstacle avoidance. Finally, future implementations on new multi-cellular hardware are discussed.
Gianluca Tempesti, Daniel Mange, Enrico Petraglio, André Stauffer, Yann Thoma
In this article, we analyze the requirements of developmental processes from the perspective of their implementation in digital hardware. After recalling the motivations for such an implementation, we concentrate separately on the two mechanisms (cellular division and cellular differentiation) that are exploited by biological systems to realize development. We then describe some of the current and projected solutions to implement such mechanisms in hardware, and conclude by analyzing the most interesting features of developmental approaches.
Gianluca Tempesti, Daniel Roggen, Eduardo Sanchez, Yann Thoma, Richard Canham, Andy Tyrrell
Evolvable Systems: From Biology to Hardware : Proceedings of the ICES 2003
In this article, we introduce the approach to the realization of ontogenetic development and fault tolerance that will be implemented in the POEtic tissue, a novel reconfigurable digital circuit dedicated to the realization of bio-inspired systems. The modelization in electronic hardware of the developmental process of multi-cellular biological organisms is an approach that could become extremely useful in the implementation of highly complex systems, where concepts such as self-organization and fault tolerance are key issues. The concepts presented in this article represent an attempt at finding a useful set of mechanisms to allow the implementation in digital hardware of a bio-inspired developmental process with a reasonable overhead.
Gianluca Tempesti, Daniel Roggen, Eduardo Sanchez, Yann Thoma, Richard Canham, Andy Tyrrell, Juan-Manuel Moreno
Proceedings of the 8th international conference on Artificial life
The implementation of bio-inspired systems in hardware has traditionally been more a matter of artistry than of method. The reasons are multiple, but one of the main problems has always been the lack of a universal platform, of a standardized architecture, and of a proper methodology for the implementation of such systems.The ideas presented in this article are the first results of a new research project, "Reconfigurable POEtic Tissue". The goal of the project is the development of a hardware platform capable of implementing systems inspired by all the three major axes (phylogenesis, ontogenesis, and epigenesis) of bio-inspiration in digital hardware.A novel cellular architecture, capable of exploiting the main features of the future POEtic tissue and compatible with a relatively automatic design methodology, is then presented.
Proceedings of the 2002 workshop on Computer architecture education
The need of co-design systems, along with the FPGA complexity, is increasing dramatically, both in industrial and academic settings. New tools are necessary to ease the development of such systems. Altera supplies a development kit with a 200'000 equivalent gates FPGA; combined with its proprietary Nios configurable processor, it allows co-design and multi-processor architecture creation. In this paper, we present a new tool, CoDeNios, which lets a developer partition a C program at the function level, and automatically generates the whole system.