The leveraging of today's unprecedented capability to manipulate biological systems by state-of-the-art computational, mathematical and engineering techniques , may profoundly affect the way we approach the solution to pressing grand challenges such as the development of sustainable green energy, next generation healthcare, etc. The conceptual cornerstone of Synthetic Biology a field very much on its infancy- is that methodologies commonly used to design and construct non-biological artefacts (e.g. computer programs, airplanes, bridges, etc) might also be mastered to create designer living entities. Computational methods for modeling in Synthetic Biology consist of a list of instructions detailing an algorithm that can be executed and whose computation resembles the behavior of the biological system under study. This computational approach to modelling biological systems has been termed executable biology. In this talk I will describe current approaches for the automated generation and testing of executable biology models for synthetic biology.
This was a colloquioum talk at the Computer Science Department, Ben-Gurion University of the Negev, Israel (30/June/2009)
Metin Bilgin is a molecular and cellular biologist with over 12 years of postgraduate research experience. He has expertise in proteomics, protein expression, and characterization. Some of his accomplishments include co-developing the first proteome chip and establishing HTP assay protocols for protein array technology. He has studied various topics like cell cycle regulation, cytochrome P450 metabolism, and nuclear hormone receptor regulated drug metabolism. Currently, he is a postdoctoral research associate studying regulation of cytochrome P450 activity by nuclear hormone receptor CAR. He aims to work for a leading life sciences research company focused on discovery and translational medicine.
This document discusses key concepts related to learning, brain development, and neuroplasticity. It defines learning as lasting changes in the functional architecture of the brain through modifications to neural connectivity and synaptic strength. Learning is influenced by both evolution and experience-dependent development. There are critical periods early in life when the brain is most plastic and receptive to certain types of learning. However, the brain remains plastic throughout life, with different forms of plasticity like experience-expectant and experience-dependent mechanisms enabling continuous learning from experiences.
Extended Compact Genetic Algorithms and Learning Classifier Systems for Dimen...Natalio Krasnogor
In this talk we demonstrate an ECGA and LCS pipeline for reducing protein alphabets from the standard 20 to 5 or less symbols without significant loss of information. The pipeline tailors the reduction to different problems thus resulting on different optimal minimal alphabets.
Evolutionary Algorithms for Self-Organising SystemsNatalio Krasnogor
Talk I gave at Ben Gurion University of the Negev in Israel on the 24rd/June/2009. These are a series of talks for the period in which I visited BGU as a distinguished visiting scientist
The document discusses research into automated design and optimization of complex systems using artificial intelligence and machine learning techniques. It describes challenges in analytically designing large physical, chemical, and biological systems. The research aims to develop sophisticated algorithms beyond exhaustive search to automatically design and optimize models of complex systems. The goal is to enable "dialing in" desired patterns and behaviors in different types of complex systems through automated design and optimization methods.
Metin Bilgin is a molecular and cellular biologist with over 12 years of postgraduate research experience. He has expertise in proteomics, protein expression, and characterization. Some of his accomplishments include co-developing the first proteome chip and establishing HTP assay protocols for protein array technology. He has studied various topics like cell cycle regulation, cytochrome P450 metabolism, and nuclear hormone receptor regulated drug metabolism. Currently, he is a postdoctoral research associate studying regulation of cytochrome P450 activity by nuclear hormone receptor CAR. He aims to work for a leading life sciences research company focused on discovery and translational medicine.
This document discusses key concepts related to learning, brain development, and neuroplasticity. It defines learning as lasting changes in the functional architecture of the brain through modifications to neural connectivity and synaptic strength. Learning is influenced by both evolution and experience-dependent development. There are critical periods early in life when the brain is most plastic and receptive to certain types of learning. However, the brain remains plastic throughout life, with different forms of plasticity like experience-expectant and experience-dependent mechanisms enabling continuous learning from experiences.
Extended Compact Genetic Algorithms and Learning Classifier Systems for Dimen...Natalio Krasnogor
In this talk we demonstrate an ECGA and LCS pipeline for reducing protein alphabets from the standard 20 to 5 or less symbols without significant loss of information. The pipeline tailors the reduction to different problems thus resulting on different optimal minimal alphabets.
Evolutionary Algorithms for Self-Organising SystemsNatalio Krasnogor
Talk I gave at Ben Gurion University of the Negev in Israel on the 24rd/June/2009. These are a series of talks for the period in which I visited BGU as a distinguished visiting scientist
The document discusses research into automated design and optimization of complex systems using artificial intelligence and machine learning techniques. It describes challenges in analytically designing large physical, chemical, and biological systems. The research aims to develop sophisticated algorithms beyond exhaustive search to automatically design and optimize models of complex systems. The goal is to enable "dialing in" desired patterns and behaviors in different types of complex systems through automated design and optimization methods.
Learning, Training, Classification, Common Sense and Exascale ComputingJoel Saltz
In this talk, I will describe work my group has carried out in development of deep learning methods that target semantic segmentation and object identification tasks in terapixel Pathology datasets and for satellite data. I will describe what we have been able to achieve, how this work can generalize to additional types of problems and will outline how exascale computing could be used to transform and integrate our methods and pipelines. I will then go on to outline broad research program in exascale computing and deep learning that promises to identify common deep learning methods for previously disparate large and extreme scale data tasks.
This document discusses data management and curation in bioinformatics. It describes Susanna-Assunta Sansone as the principal investigator and team leader at the University of Oxford e-Research Centre, where her team works on data management, biocuration, software development, databases, and community standards and ontologies for various domains including toxicology, health, and agriculture. The document promotes the importance of data standards to enable data sharing and reproducibility in bioscience research.
The document discusses reproducible bioscience data. It describes Susanna-Assunta Sansone as a principal investigator and team leader at the University of Oxford e-Research Centre who gives a presentation on policies, communities, and standards around reproducible bioscience data. The presentation covers topics like preserving institutional memory, utilizing public data, and addressing reproducibility and reuse of public data through community standards and structured data annotation.
P Systems Model Optimisation by Means of Evolutionary Based Search ...Natalio Krasnogor
This document discusses using evolutionary algorithms to optimize parameters in P systems, which are computational models of biological cells. Four test cases of increasing difficulty are used to compare different algorithms. The results show that genetic algorithms, differential evolution, and opposition-based differential evolution perform better for problems with fewer parameters, while variable neighbourhood search algorithms perform better for the largest problem with 38 parameters. This is because the evolutionary algorithms are less efficient at optimizing large populations within the limited evaluation budget, whereas variable neighbourhood search focuses on a single solution.
Journal Review - The Emerging role of in vitro electrophysiological methods i...Blessing Umoudit
This document outlines various in vitro approaches and models used in central nervous system (CNS) safety pharmacology studies. It discusses electrophysiological techniques like patch clamp and two electrode voltage clamp. It also describes commonly used in vitro tissue models like cell lines, primary neuronal cultures, brain slices, and 3D neuronal models. Emerging models for assessing seizure liability and memory effects are mentioned. Overall the document provides an overview of techniques and their limitations in predicting CNS effects, noting the need for continued improvements to account for biological complexity.
This document provides an introduction to next-generation sequencing (NGS) technologies. It discusses the history of DNA sequencing technologies leading up to NGS, including Sanger sequencing. It then describes the key principles of several major NGS platforms, including how they achieve massively parallel sequencing using amplification and signal detection. The document notes challenges of NGS like short read lengths, coverage depth needs, and large data volumes. It also outlines common applications of NGS data like variant detection and discusses future prospects.
Berlin center for genome based bioinformatics koch05Slava Karpov
This document summarizes the research activities of the Berlin Center for Genome Based Bioinformatics at the Technical University of Applied Sciences. The center focuses on modeling and analyzing biochemical systems using Petri nets. Specifically, it has modeled central metabolic pathways like glycolysis and developed Petri net tools to validate biochemical networks and analyze the behavior of large networks like E. coli metabolism.
This document discusses optimizing cancer genomics pipelines on parallel supercomputers. It describes using a custom-built pipeline of open-source genomics codes to analyze RNA-Seq data from Adenoid Cystic Carcinoma tumor samples. Preliminary results show parallelizing the pipeline on a supercomputer by splitting the input data and running parts in parallel reduced processing time compared to running on a single node. Further optimization of the pipeline and testing on more data is planned.
The World of Widgets – An Important Step Towards a Personalized Learning Envi...Martin Ebner
This document discusses the development of a personalized learning environment (PLE) at Graz University of Technology. Usability tests were conducted with technical and non-technical users, finding that the PLE concept was unfamiliar and introductions were needed. Tracking usage data showed the most used and activated widgets, which could be improved using a K-selection strategy. The PLE aims to provide personalization, mobile access, and allow combining widgets to create new functionalities, representing an evolution guided by principles of variation, selection, and recombination.
Processing Amplicon Sequence Data for the Analysis of Microbial CommunitiesMartin Hartmann
This document provides an overview of next-generation sequencing (NGS) technologies and their usefulness for analyzing microorganisms associated with plants. It discusses how NGS methods allow addressing previously impossible questions about the composition, function, and interactions of microbial communities in environments like the rhizosphere and phyllosphere. While powerful, NGS platforms have limitations that can introduce errors or biases, but methods exist to overcome these issues. The review highlights applications of NGS in metagenomic studies of plant-associated microbiomes and how these new techniques are transforming the field.
This is an introduction to a knowledge engineering methodology called 'Knowledge Engineering from Experimental Design' (KEfED). This methodology provides a powerful, intuitive method for modeling the design of scientific experiments and provides the foundation for work at the Biomedical Knowledge Engineering Group at the Information Sciences Institute (run by Gully Burns)
Spatial Analysis On Histological Images Using SparkJen Aman
This document describes using Spark for spatial analysis of histological images to characterize the tumor microenvironment. The goal is to provide actionable data on the location and density of immune cells and blood vessels. Over 100,000 objects are annotated in each whole slide image. Spark is used to efficiently calculate over 5 trillion pairwise distances between objects within a neighborhood window. This enables profiling of co-localization and spatial clustering of objects. Initial results show the runtime scales linearly with the number of objects. Future work includes integrating clinical and genomic data to characterize variation between tumor types and patients.
This article compares four test methods for measuring damping properties of materials using piezoelectric transducers: the Central Impedance Method, Modified Oberst Method, Seismic Response Method, and simply supported beam method. Experiments were conducted on aluminum beams and ECCS-PET layers under controlled temperature conditions. Results for damping loss factor and Young's modulus obtained from each method were compared to study variability. The Central Impedance Method showed the lowest statistical dispersion. Non-resonant simply supported beam method allows characterization of materials at very low frequencies without size limitations of resonant methods.
Thomas Charles Ferree has over 25 years of experience in signal processing, algorithm development, and neuroscience research. He has a PhD in Physics from the University of Colorado and has held positions at several universities and research institutions. His research has focused on developing algorithms and models for analyzing EEG, EIT, and other biological signal data to study visual attention, stroke detection, and the neurological effects of various stimuli. He has extensive experience developing software and analyzing data across various computing platforms.
This presentation explains the meaning of curation and includes an introduction to the Apollo genome annotation editing tool and its curation environment.
Robust Feature Learning with Deep Neural Networks
http://snu-primo.hosted.exlibrisgroup.com/primo_library/libweb/action/display.do?tabs=viewOnlineTab&doc=82SNU_INST21557911060002591
ISMB2014読み会 イントロ + Deep learning of the tissue-regulated splicing codeKengo Sato
This document summarizes an experiment using deep neural networks (DNNs) to predict alternative splicing patterns in mouse tissues from RNA-seq data. The DNN model contains three hidden layers and jointly represents genomic sequence features and tissue types to predict splicing percentages and changes across tissues. Hyperparameters were optimized using 5-fold cross-validation on AUC. The trained DNN was able to accurately predict splicing patterns for 11,019 exons in 5 mouse tissues, outperforming previous models like Bayesian neural networks and multinomial logistic regression.
Course: Bioinformatics for Biomedical Research (2014).
Session: 2.1.2- Next Generation Sequencing. Technologies and Applications. Part II: NGS Applications I.
Statistics and Bioinformatisc Unit (UEB) & High Technology Unit (UAT) from Vall d'Hebron Research Institute (www.vhir.org), Barcelona.
Designing for Addressability, Bio-orthogonality and Abstraction Scalability a...Natalio Krasnogor
This document discusses designing DNA and RNA origami for physiological conditions and scalability. It describes using a De Bruijn sequence as a scaffold for DNA and RNA origami that provides unique addressability and is bio-orthogonal. Experiments are discussed where an RNA De Bruijn sequence scaffold was electroporated into E. coli to test its stability in vivo. The document also covers designing RNA origami for physiological conditions using chemically modified RNA and a split Broccoli aptamer to monitor assembly in living cells. The goal is to design origami that can be expressed and function within physiological environments and biological systems.
Learning, Training, Classification, Common Sense and Exascale ComputingJoel Saltz
In this talk, I will describe work my group has carried out in development of deep learning methods that target semantic segmentation and object identification tasks in terapixel Pathology datasets and for satellite data. I will describe what we have been able to achieve, how this work can generalize to additional types of problems and will outline how exascale computing could be used to transform and integrate our methods and pipelines. I will then go on to outline broad research program in exascale computing and deep learning that promises to identify common deep learning methods for previously disparate large and extreme scale data tasks.
This document discusses data management and curation in bioinformatics. It describes Susanna-Assunta Sansone as the principal investigator and team leader at the University of Oxford e-Research Centre, where her team works on data management, biocuration, software development, databases, and community standards and ontologies for various domains including toxicology, health, and agriculture. The document promotes the importance of data standards to enable data sharing and reproducibility in bioscience research.
The document discusses reproducible bioscience data. It describes Susanna-Assunta Sansone as a principal investigator and team leader at the University of Oxford e-Research Centre who gives a presentation on policies, communities, and standards around reproducible bioscience data. The presentation covers topics like preserving institutional memory, utilizing public data, and addressing reproducibility and reuse of public data through community standards and structured data annotation.
P Systems Model Optimisation by Means of Evolutionary Based Search ...Natalio Krasnogor
This document discusses using evolutionary algorithms to optimize parameters in P systems, which are computational models of biological cells. Four test cases of increasing difficulty are used to compare different algorithms. The results show that genetic algorithms, differential evolution, and opposition-based differential evolution perform better for problems with fewer parameters, while variable neighbourhood search algorithms perform better for the largest problem with 38 parameters. This is because the evolutionary algorithms are less efficient at optimizing large populations within the limited evaluation budget, whereas variable neighbourhood search focuses on a single solution.
Journal Review - The Emerging role of in vitro electrophysiological methods i...Blessing Umoudit
This document outlines various in vitro approaches and models used in central nervous system (CNS) safety pharmacology studies. It discusses electrophysiological techniques like patch clamp and two electrode voltage clamp. It also describes commonly used in vitro tissue models like cell lines, primary neuronal cultures, brain slices, and 3D neuronal models. Emerging models for assessing seizure liability and memory effects are mentioned. Overall the document provides an overview of techniques and their limitations in predicting CNS effects, noting the need for continued improvements to account for biological complexity.
This document provides an introduction to next-generation sequencing (NGS) technologies. It discusses the history of DNA sequencing technologies leading up to NGS, including Sanger sequencing. It then describes the key principles of several major NGS platforms, including how they achieve massively parallel sequencing using amplification and signal detection. The document notes challenges of NGS like short read lengths, coverage depth needs, and large data volumes. It also outlines common applications of NGS data like variant detection and discusses future prospects.
Berlin center for genome based bioinformatics koch05Slava Karpov
This document summarizes the research activities of the Berlin Center for Genome Based Bioinformatics at the Technical University of Applied Sciences. The center focuses on modeling and analyzing biochemical systems using Petri nets. Specifically, it has modeled central metabolic pathways like glycolysis and developed Petri net tools to validate biochemical networks and analyze the behavior of large networks like E. coli metabolism.
This document discusses optimizing cancer genomics pipelines on parallel supercomputers. It describes using a custom-built pipeline of open-source genomics codes to analyze RNA-Seq data from Adenoid Cystic Carcinoma tumor samples. Preliminary results show parallelizing the pipeline on a supercomputer by splitting the input data and running parts in parallel reduced processing time compared to running on a single node. Further optimization of the pipeline and testing on more data is planned.
The World of Widgets – An Important Step Towards a Personalized Learning Envi...Martin Ebner
This document discusses the development of a personalized learning environment (PLE) at Graz University of Technology. Usability tests were conducted with technical and non-technical users, finding that the PLE concept was unfamiliar and introductions were needed. Tracking usage data showed the most used and activated widgets, which could be improved using a K-selection strategy. The PLE aims to provide personalization, mobile access, and allow combining widgets to create new functionalities, representing an evolution guided by principles of variation, selection, and recombination.
Processing Amplicon Sequence Data for the Analysis of Microbial CommunitiesMartin Hartmann
This document provides an overview of next-generation sequencing (NGS) technologies and their usefulness for analyzing microorganisms associated with plants. It discusses how NGS methods allow addressing previously impossible questions about the composition, function, and interactions of microbial communities in environments like the rhizosphere and phyllosphere. While powerful, NGS platforms have limitations that can introduce errors or biases, but methods exist to overcome these issues. The review highlights applications of NGS in metagenomic studies of plant-associated microbiomes and how these new techniques are transforming the field.
This is an introduction to a knowledge engineering methodology called 'Knowledge Engineering from Experimental Design' (KEfED). This methodology provides a powerful, intuitive method for modeling the design of scientific experiments and provides the foundation for work at the Biomedical Knowledge Engineering Group at the Information Sciences Institute (run by Gully Burns)
Spatial Analysis On Histological Images Using SparkJen Aman
This document describes using Spark for spatial analysis of histological images to characterize the tumor microenvironment. The goal is to provide actionable data on the location and density of immune cells and blood vessels. Over 100,000 objects are annotated in each whole slide image. Spark is used to efficiently calculate over 5 trillion pairwise distances between objects within a neighborhood window. This enables profiling of co-localization and spatial clustering of objects. Initial results show the runtime scales linearly with the number of objects. Future work includes integrating clinical and genomic data to characterize variation between tumor types and patients.
This article compares four test methods for measuring damping properties of materials using piezoelectric transducers: the Central Impedance Method, Modified Oberst Method, Seismic Response Method, and simply supported beam method. Experiments were conducted on aluminum beams and ECCS-PET layers under controlled temperature conditions. Results for damping loss factor and Young's modulus obtained from each method were compared to study variability. The Central Impedance Method showed the lowest statistical dispersion. Non-resonant simply supported beam method allows characterization of materials at very low frequencies without size limitations of resonant methods.
Thomas Charles Ferree has over 25 years of experience in signal processing, algorithm development, and neuroscience research. He has a PhD in Physics from the University of Colorado and has held positions at several universities and research institutions. His research has focused on developing algorithms and models for analyzing EEG, EIT, and other biological signal data to study visual attention, stroke detection, and the neurological effects of various stimuli. He has extensive experience developing software and analyzing data across various computing platforms.
This presentation explains the meaning of curation and includes an introduction to the Apollo genome annotation editing tool and its curation environment.
Robust Feature Learning with Deep Neural Networks
http://snu-primo.hosted.exlibrisgroup.com/primo_library/libweb/action/display.do?tabs=viewOnlineTab&doc=82SNU_INST21557911060002591
ISMB2014読み会 イントロ + Deep learning of the tissue-regulated splicing codeKengo Sato
This document summarizes an experiment using deep neural networks (DNNs) to predict alternative splicing patterns in mouse tissues from RNA-seq data. The DNN model contains three hidden layers and jointly represents genomic sequence features and tissue types to predict splicing percentages and changes across tissues. Hyperparameters were optimized using 5-fold cross-validation on AUC. The trained DNN was able to accurately predict splicing patterns for 11,019 exons in 5 mouse tissues, outperforming previous models like Bayesian neural networks and multinomial logistic regression.
Course: Bioinformatics for Biomedical Research (2014).
Session: 2.1.2- Next Generation Sequencing. Technologies and Applications. Part II: NGS Applications I.
Statistics and Bioinformatisc Unit (UEB) & High Technology Unit (UAT) from Vall d'Hebron Research Institute (www.vhir.org), Barcelona.
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Designing for Addressability, Bio-orthogonality and Abstraction Scalability a...Natalio Krasnogor
This document discusses designing DNA and RNA origami for physiological conditions and scalability. It describes using a De Bruijn sequence as a scaffold for DNA and RNA origami that provides unique addressability and is bio-orthogonal. Experiments are discussed where an RNA De Bruijn sequence scaffold was electroporated into E. coli to test its stability in vivo. The document also covers designing RNA origami for physiological conditions using chemically modified RNA and a split Broccoli aptamer to monitor assembly in living cells. The goal is to design origami that can be expressed and function within physiological environments and biological systems.
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This is a plenary talk I gave at the 2018 International Conference on Information Processing and Management of Uncertainty in Knowledge-Based Systems in Cadiz, Spain
The document discusses recent advances in accelerating synthetic biology through computational and hardware methods. It describes developing biological programming languages to specify combinatorial DNA libraries and using microfluidic devices to build these libraries at a desktop scale. It also discusses using machine learning for data analysis to speed up computational simulations in synthetic biology.
The Infobiotics BioProgramming Language & Workbench provides a computer-aided design environment for synthetic biology. It integrates simulation, verification, and compilation capabilities through an iterative workflow. The Infobiotics Language (IBL) allows users to define synthetic biology parts, rules, and devices. IBL supports abstraction, encapsulation, and hierarchical organization. The workbench performs stochastic simulation, model checking for verification, and biomatter compilation to generate DNA sequences. It aims to enable more reliable engineering of synthetic biological circuits.
The document introduces bio computing and discusses how cells can be modeled as computing devices. It outlines key topics including using P systems to represent cellular computation and examples of biocomputing. Specific concepts covered include modeling genetic transcriptional networks and common network motifs that are evolutionarily preferred. Membrane structures and transport mechanisms in P systems are also summarized.
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This document discusses using porphyrin-based nano-tiles for evolvable designs and computation through self-assembly. It outlines research on:
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2) Modeling self-assembly of porphyrin molecules with different binding strengths using kinetic Monte Carlo simulations to predict experimental outcomes.
3) Analyzing self-assembled structures from the simulations using metrics like Minkowski functionals and Kolmogorov complexity to characterize computation and information processing during self-assembly.
Plenary Speaker slides at the 2016 International Workshop on Biodesign Automa...Natalio Krasnogor
In this talk I discuss recent work done in my lab and with collaborators abroad that contributes towards accelerating the specify -> design -> model -> build -> test & iterate biological engineering cycle. This will describe advances in biological programming languages for specifying combinatorial DNA libraries, the utilisation of off-the-shelf microfluidic devices to build the DNA libraries as well as data analysis techniques to accelerate computational simulations
Memetic Algorithms have become one of the key methodologies behind solvers that are capable of tackling very large, real-world, optimisation problems. They are being actively investigated in research institutions as well as broadly applied in industry. In this talk we provide a pragmatic guide on the key design issues underpinning Memetic Algorithms (MA) engineering. We begin with a brief contextual introduction to Memetic Algorithms and then move on to define a Pattern Language for MAs. For each pattern, an associated design issue is tackled and illustrated with examples from the literature. We then fast forward to the future and mention what, in our mind, are the key challenges that scientistis and practitioner will need to face if Memetic Algorithms are to remain a relevant technology in the next 20 years.
Darwin’s Magic: Evolutionary Computation in Nanoscience, Bioinformatics and S...Natalio Krasnogor
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These slides were used for a tutorial I gave at GECCO 2010. These are similar, yet not identical, to the other tutorials. The keynote file is too large for slideshare but if anybody needs the original I would be happy to provide a url from where to download it.
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These slides are part of a presentation I gave on March 2010 at the BioInformatics and Genome Research Open Club at the Weizmann Institute of Science, Israel.
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Chapter wise All Notes of First year Basic Civil Engineering
Syllabus
Chapter-1
Introduction to objective, scope and outcome the subject
Chapter 2
Introduction: Scope and Specialization of Civil Engineering, Role of civil Engineer in Society, Impact of infrastructural development on economy of country.
Chapter 3
Surveying: Object Principles & Types of Surveying; Site Plans, Plans & Maps; Scales & Unit of different Measurements.
Linear Measurements: Instruments used. Linear Measurement by Tape, Ranging out Survey Lines and overcoming Obstructions; Measurements on sloping ground; Tape corrections, conventional symbols. Angular Measurements: Instruments used; Introduction to Compass Surveying, Bearings and Longitude & Latitude of a Line, Introduction to total station.
Levelling: Instrument used Object of levelling, Methods of levelling in brief, and Contour maps.
Chapter 4
Buildings: Selection of site for Buildings, Layout of Building Plan, Types of buildings, Plinth area, carpet area, floor space index, Introduction to building byelaws, concept of sun light & ventilation. Components of Buildings & their functions, Basic concept of R.C.C., Introduction to types of foundation
Chapter 5
Transportation: Introduction to Transportation Engineering; Traffic and Road Safety: Types and Characteristics of Various Modes of Transportation; Various Road Traffic Signs, Causes of Accidents and Road Safety Measures.
Chapter 6
Environmental Engineering: Environmental Pollution, Environmental Acts and Regulations, Functional Concepts of Ecology, Basics of Species, Biodiversity, Ecosystem, Hydrological Cycle; Chemical Cycles: Carbon, Nitrogen & Phosphorus; Energy Flow in Ecosystems.
Water Pollution: Water Quality standards, Introduction to Treatment & Disposal of Waste Water. Reuse and Saving of Water, Rain Water Harvesting. Solid Waste Management: Classification of Solid Waste, Collection, Transportation and Disposal of Solid. Recycling of Solid Waste: Energy Recovery, Sanitary Landfill, On-Site Sanitation. Air & Noise Pollution: Primary and Secondary air pollutants, Harmful effects of Air Pollution, Control of Air Pollution. . Noise Pollution Harmful Effects of noise pollution, control of noise pollution, Global warming & Climate Change, Ozone depletion, Greenhouse effect
Text Books:
1. Palancharmy, Basic Civil Engineering, McGraw Hill publishers.
2. Satheesh Gopi, Basic Civil Engineering, Pearson Publishers.
3. Ketki Rangwala Dalal, Essentials of Civil Engineering, Charotar Publishing House.
4. BCP, Surveying volume 1
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Building Executable Biology Models for Synthetic Biology
1. Building Executable Biology Models for
Synthetic Biology
Natalio Krasnogor
ASAP - Interdisciplinary Optimisation Laboratory
School of Computer Science
Centre for Integrative Systems Biology
School of Biology
Centre for Healthcare Associated Infections
Institute of Infection, Immunity & Inflammation
University of Nottingham
1 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
2. Based on
F. J. Romero-Campero, J. Twycross, M. Camara, M. Bennett, M. Gheorghe,
and N. Krasnogor. Modular assembly of cell systems biology models using
p systems. International Journal of Foundations of Computer Science,
2009.
F.J. Romero-Camero and N. Krasnogor. An approach to biomodel
engineering based on p systems. In Proceedings of Computation In Europe
(CIE 2009), 2009
F. Romero-Campero, H.Cao, M. Camara, and N. Krasnogor. Structure and
parameter estimation for cell systems biology models. In Maarten Keijzer
et.al, editor, Proceedings of the Genetic and Evolutionary Computation
Conference (GECCO-2008), pages 331-338. ACM Publisher, 2008. This
paper won the Best Paper award at the Bioinformatics track.
Analysis of Alternative Fitness Methods for the Evolutionary Synthesis of
Cell Systems Biology Models. F. Romero-Campero, H.Cao, M. Camara, and
N. Krasnogor. Submitted.
2 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
3. Outline
•Brief Introduction to Computational Modeling
•Modeling for Top Down SB
•Executable Biology
•Automated Model Synthesis and Optimisation
•Conclusions
3 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
4. Synthetic Biology
• Aims at designing, constructing and developing artificial biological
systems
•Offers new routes to ‘genetically modified’ organisms, synthetic living
entities, smart drugs and hybrid computational-biological devices.
• Potentially enormous societal impact, e.g., healthcare, environmental
protection and remediation, etc
• Synthetic Biology's basic assumption:
• Methods commonly used to build non-biological systems could
also be use to specify, design, implement, verify, test, deploy
and maintain novel synthetic biosystems.
• These method come from computer science, engineering and
maths.
• Modelling and optimisation run through all of the above.
4 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
5. Models and Reality
•The use of models is intrinsic to any
scientific activity.
•Models are abstractions of the real-world
that highlight some key features while
ignoring others that are assumed to be not
relevant.
•A model should not be seen or presented
as representations of the truth, but instead
5 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
6. The goals of Modelling
•To capture the essential features of
a biological entity/phenomenon
•To disambiguate the understanding
behind those features and their
interactions
•To move from qualitative knowledge
towards quantitative knowledge
6 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
7. Modeling relies on rigorous computational,
engineering and mathematical tools &
techniques
However, the act of modeling remains at the
interface between art and science
Undoubtedly, a multidisciplinary endeavour
7 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
8. Modelling Approaches
There exist many modelling approaches, each with its
advantages and disadvantages.
Macroscopic, Microscopic and Mesoscopic
Quantitative and qualitative
Discrete and Continuous
Deterministic and Stochastic
Top-down or Bottom-up
8 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
9. Tools Suitability and Cost
From [D.E Goldberg, 2002] (adapted):
“Since science and math are in the description
business, the model is the thing…The engineer
or inventor has much different motives. The
engineered object is the thing” ε, error
Synthetic Biologist
Computer Scientist/Mathematician
C, cost of modelling
9 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
10. Modelling Frameworks
•Denotational Semantics Models:
Set of equations showing relationships between molecular
quantities and how they change over time.
They are approximated numerically.
(I.e. Ordinary Differential Equations, PDEs, etc)
•Operational Semantics Models:
Algorithm (list of instructions) executable by an abstract
machine whose computation resembles the behaviour of the
system under study. (i.e. Finite State Machine)
Jasmin Fisher and Thomas Henzinger. Executable cell biology. Nature Biotechnology, 25, 11, 1239-1249
(2008)
10 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
11. The Scale Separation Map
• With sufficient data each process can be
assigned its space-time region
unambiguously
Couplings, e.g. F • A given process may well have its Δx
(respectively Δt) > than another’s ξA
(respectively τA)
Spatial scale (log)
• Hence different processes in the SSM might
require different modelling techniques
Temporal scale (log)
11 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
12. Even within a single cell the space & time
scale separations are important
E.g.:
• Within a cell the dissociation
constants of DNA/ transcription
factor binding to specific/non-
specific sites differ by 4-6 orders of
magnitude
• DNA protein binding occurs at 1-10s
time scale very fast in comparison
to a cell’s life cycle.
[F.J. Romero Campero, 2007]
12 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
13. Stochasticity in Cellular Systems
Most commonly recognised sources of noise in cellular system are low
number of molecules and slow molecular interactions.
Over 80% of genes in E. coli express fewer than a hundred proteins per cell.
Mesoscopic, discrete and stochastic approaches are more suitable:
Only relevant molecules are taken into account.
Focus on the statistics of the molecular interactions and how often they
take place.
Mads Karn et al. Stochasticity in Gene Expression: From Theories to Phenotypes. Nature Reviews, 6,
451-464 (2005)
Purnananda Guptasarma. Does replication-induced transcription regulate synthesis of the myriad low
copy number poteins of E. Coli. BioEssays, 17, 11, 987-997
13 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
14. It thus makes sense to use methodologies
designed to cope with complex,
concurrent, interactive systems of parts as
found in computer sciences (e.g.):
Petri Nets
Process Calculi
P-Systems
14 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
15. InfoBiotics
www.infobiotic.net
•The utilisation of cutting-edge information
processing techniques for biological modelling and
synthesis
•The understanding of life itself as multi-scale
(Spatial/Temporal) information processing systems
•Composed of 3 key components:
•Executable Biology (or other modeling
techniques)
•Automated Model and Parameter Estimation
•Model Checking (and other formal analysis)
15 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
16. Modeling in Systems & Synthetic Biology
Systems Biology Synthetic Biology
Colonies
• Understanding •Control
• Integration • Design
• Prediction • Engineering
• Life as it is •Life as it could be
Cells
Computational modelling to Computational modelling to
elucidate and characterise engineer and evaluate
modular patterns exhibiting possible cellular designs
robustness, signal filtering, exhibiting a desired
amplification, adaption, behaviour by combining well
error correction, etc. studied and characterised
Networks cellular modules
16 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
17. Model Development
From [E. Klipp et al, Systems Biology in Practice,
2005]
1. Formulation of the problem
2. Verification of available information
3. Selection of model structure
4. Establishing a simple model
5. Sensitivity analysis
6. Experimental tests of the model predictions
7. Stating the agreements and divergences between
experimental and modelling results
8. Iterative refinement of model
17 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
18. Outline
•Brief Introduction to Computational Modeling
•Modeling for Top Down SB
•Executable Biology
•Automated Model Synthesis and Optimisation
•Conclusions
18 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
19. Executable Biology with P systems
Field of membrane computing initiated by
Gheorghe Păun in 2000
Inspired by the hierarchical membrane structure
of eukaryotic cells
A formal language: precisely defined and
machine processable
An executable biology methodology
19 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
20. Distributed and parallel rewritting systems in
compartmentalised hierarchical structures.
Objects
Compartments
Rewriting Rules
• Computational universality and efficiency.
• Modelling Framework
20 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
21. Stochastic P Systems
21 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
22. Rewriting Rules
used by Multi-volume Gillespie’s algorithm
22 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
23. Molecular Interactions
Inside Compartments
23 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
24. Passive Diffusion of Molecules
24 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
25. Signal Sensing and
Active Transport
25 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
26. Specification of Transcriptional
Regulatory Networks
26 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
27. Scalability through Modularity
27 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
28. Modularity in Gene Regulatory Networks
According to E. Davidson
functional cis-regulatory modules
are nonrandom clusters of target
binding sites for transcription
factors regulating the same gene
or operon.
A library of modules
corresponding to promoters of
well studied genes. The activity of
these promoters have been
modelled mechanistically in terms
of rewriting rules representing TF
binding and debinding and
transcription initiation.
E. Davidson, The Regulatory Genome, Gene Regulatory Networks in Development and Evolution,
Elsevier.
28 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
29. Modelling Individual Cells
An individual cell is represented as a P system, a set of compartments
where specific objects describing molecular species are placed.
The gene regulatory networks in each cell are represented as a collection
of modules and rewriting rules.
29 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
30. Using P systems modules one can model a large variety of
commonly occurring BRN:
Gene Regulatory Networks
Signaling Networks
Metabolic Networks
This can be done in an incremental way.
F. J. Romero-Campero, J. Twycross, M. Camara, M. Bennett, M. Gheorghe, and N. Krasnogor.
Modular assembly of cell systems biology models using p systems. International Journal of
Foundations of Computer Science, 2009
30 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
31. InfoBiotics
Pipeline
31 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
32. Quick Demo
Simulator-results-rescaled.html
Cie-model22-rescaled.html
32 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
33. Outline
•Brief Introduction to Computational Modeling
•Modeling for Top Down SB
•Executable Biology
•Automated Model Synthesis and Optimisation
•Conclusions
33 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
34. Automated Model Synthesis and Optimisation
Modeling is an intrinsically difficult process
It involves “feature selection” and disambiguation
Model Synthesis requires
design the topology or structure of the system in
terms of molecular interactions
estimate the kinetic parameters associated with
each molecular interaction
All the above iterated
34 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
35. Large Literature on Model Synthesis
• Mason et al. use a random Local Search (LS) as the mutation to
evolve electronic networks with desired dynamics
• Chickarmane et al. use a standard GA to optimize the kinetic
parameters of a population of ODE-based reaction networks having
the desired topology.
• Spieth et al. propose a Memetic Algorithm to find gene regulatory
networks from experimental DNA microarray data where the network
structure is optimized with a GA and the parameters are optimized
with an Evolution Strategy (ES).
• Jaramillo et al. use Simulated Annealing as the main search strategy
for model inference based on (O)DEs
35 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
36. Evolutionary Algorithms for Automated
Model Synthesis and Optimisation
EA are potentially very useful for AMSO
There’s a substantial amount of work on:
using GP-like systems to evolve executable
structures
using EAs for continuous/discrete
optimisation
An EA population represents alternative
models (could lead to different experimental
setups)
EAs have the potential to capture, rather than
avoid, evolvability of models
36 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
37. Nested EA for Model Synthesis
F. Romero-Campero, H.Cao, M.
Camara, and N. Krasnogor.
Structure and parameter
estimation for cell systems
biology models. Proceedings of
the Genetic and Evolutionary
Computation Conference
(GECCO-2008), pages
331-338. ACM Publisher, 2008.
Best Paper award at the
Bioinformatics track.
37 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
38. Fitness Evaluation
38 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
39. The Objective (Fitness)
Function
• Multiple time-series
per target
• Different time series
have very different
profiles, e.g., maxima
occur at different
times/places
• Transient states
(sometimes) as
important as steady
states
•RMSE might mislead
search
H. Cao, F. Romero-Campero, M.Camara, N.Krasnogor. Analysis of Alternative Fitness Methods for the
Evolutionary Synthesis of Cell Systems Biology Models. Submitted (2009)
39 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
40. A Few Examples
40 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
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41. 41 /57
Problem Specification
Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
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43. Results Study Case 4
43 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
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48. 48 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
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49. Target
49 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
50. Target
50 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
51. The fact that this algorithm produces alternative models
for a specific biological signature is very encouraging as
it could help biologists to design new experiments to
discriminate among competing hypothesis (models).
Comparing results by only using the elementary
modules and by adding newly found modules to the
library shows the obvious advantage of the incremental
methodology with modules.
This points out the great potential to automatically design
more complex cellular models in the future by using a
modular approach.
51 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
52. Outline
•Brief Introduction to Computational Modeling
•Modeling for Top Down SB
•Executable Biology
•Automated Model Synthesis and Optimisation
•Conclusions
52 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
53. Summary & Conclusions
This talk has focused on an integrative methodology,
InfoBiotics, for Systems & Synthetic Biology
Executable Biology
Parameter and Model Structure Discovery
Model Checking
Computational models (or executable in Fisher &
Henzinger’s jargon) adhere to (a degree) to an operational
semantics.
Refer to the excellent review [Fisher & Henzinger, Nature
Biotechnology, 2007]
53 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
54. Summary & Conclusions
Computational models can thus be executed
(quite a few tools out there, lots still missing)
Quantitative VS qualitative modelling:
computational models can be very useful even
when not every detail about a system is known.
Missing Parameters/model structures can
sometimes be fitted with optimisation strategies
(e.g. COPASI, GAs, etc)
Computational models can be analysed by
model checking: thus they can be used for
testing hypothesis and expanding experimental
data in a principled way
54 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
55. Summary & Conclusions
Synthetising Synthetic Biology Models is more like evolving
general GP programs and less like fitting regresion or inter/extra-
polation
We evolve executable structures
These are noisy and expensive to execute
Like in GP programs, executable biology models might achieve
similar behaviour through different program “structure”
Prone to bloat
Like in GP, complex relation between diversity and solution
quality
However, diverse solutions of similar fit might lead to interesting
experimental routes
Co-desig of models and wetware.
55 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
56. Acknowledgements
Members of my team working on SB2
EP/E017215/1
Jonathan Blake Integrated Environment
EP/D021847/1
Hongqing Cao Machine Learning & Optimisation BB/F01855X/1
BB/D019613/1
Francisco Romero-Campero Modeling & Model Checking
Dissipative Particle Dynamics My colleagues in the Centre for
James Smaldon
Biomolecular Sciences and the
Centre for Plant Integrative Biology
Jamie Twycross Stochastic Simulations at Nottingham
Thanks also go to:
Ben Gurion University of the Negev’s
Distinguished Scientists Visitor Program
Professor Dr. Moshe Sipper
56 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009
57. Any Questions?
• www.infobiotic.org
• www.synbiont.org Become a member and have access to $$$ for
engaging in SB research. Contact me if interested
57 /57 Ben-Gurion University of the Negev - June 23rd to July 5th 2009 - Distinguished Scientist Visitor Program - Beer Sheva, Israel
Tuesday, 30 June 2009