text:
Metabolomics/Introduction to Metabolomics/Relationship to Traditional Metabolism

Back to Book Table of Contents: Metabolomics Next chapter: Metabolites Go to History

=Introduction=

Relationship of Metabolomics to Traditional Metabolism

The traditional methodology of analytical biochemistry as it relates to metabolism is slowly and carefully being replaced by the newer and far more effective methods of the new field Metabolomics. This is being done simply because the old methods of classic metabolism can't yield the type of data needed for the aims of systems biology and metabolic engineering by concentrating on single pathways and only minor interactions between them. In comparison, Metabolomics is far more effective for a wide variety of systems biology concerns, like nutrigenomics and toxicology. Previously all attempts had been concentrated on proteomics and genomics because keeping track of the entire metabolome was an extraordinarily difficult task. But as more cheap and effective methods of doing this were developed Metabolomics steadily became more effective than even proteomics and genomics. The differences are strong enough to necessitate a rethinking of the experimental processes and procedures and the integrations of data sharing and acquisition. Even the nomenclature and terminology is undergoing an overhaul showing just how much of a radical change in focus and method Metabolomics is. This doesn't mean that the reductionism method is useless by any means. Parts of the biochemical processes and the metabolic systems of organisms can be better understood through reductionism Classical analytical biochemistry for metabolism is not being replaced. It just has a brand new systems orientated partner in the new and exciting biological and biochemistry fields of study and application that are opening up even now.

Phenylalanine Metabolism

Metabolomics relationship to traditional metabolism is not strictly for the biochemistry or proteomics to analyze. Certainly many other biological specialists can look at a metabolic pathway and relate to their specialized field. Whether there is an increase or decrease of intermediates concentration or a blockade or degrade of a metabolites, it will certainly have an effect over all of the biology of that system. Consider the metabolism of phenylalanine. Our body cannot synthesize phenylalanine and must obtain it through our diet. Phenylalanine called L-phenylalanine that is found in all proteins (beef, chicken, fish, pork, yogurt, eggs...). The other forms of phenylalanine are D-phenylalanine and D/L-phenylalanine, a blend of 50/50 portion of L and D-phenylalanine. D-phenylalanine is not found in food but can be synthesized in the lab.

Phenylalanine is an important amino acid because the body converts phenylalanine into tyrosine which is metabolize into acetoacetic acid, a ketone body, and fumeric acid, an organic acid that is an intermediate in the citric acid cycle. Phenylalanine is an essential amino acid because it helps synthesize the right intermediates as part of the body energy synthesis mechanism.If we consider the metabolism of phenylalanine, every single intermediate is important in this pathway. If we consider the metabolism of phenylalanine, every single intermediate is important in this pathway.

What would a geneticist say?

If there is a mutation in a gene that cause an enzyme to become dysfunctional in the pathway will result in the accumulation of an intermediate in the blood, which inevitably causes a genetic disease. When this occurs, the accumulation of an intermediate can either burst the cell or cause the body to find a way to break down the excess which both can invoke serious diseases and organ damage. For example, phenylalanine hydroxylase is the enzyme that converts of phenylalanine into tyrosine. If a mutation occurred that made phenylalanine hydroxylase to be dysfunctional, meaning it does not allow phenylalanine to be convert into tyrosine, there will be an accumulation of phenylalanine in the blood. The body has to find a way to get rid of the excess phenylalanine so phenylalanine is converted into phenylketone, a toxic intermediate that causes the disease phenylketonuria (PKU, 12q22-q24 mutation). The symptoms of a person with PKU are a mousy odor in the urine, irreversible psychomotor retardation and autism. Consider the enzyme homogenistic acid oxidase that converts homogenistic acid into maleylacetoacetic acid in the phenylalanine metabolism. If there is a mutation that limited the function of this enzyme, the result is the accumulation of homogenistic acid in the blood. This give rise a genetic disease known as alkaptonuria (AKU, 3q21-q23 mutation). Sir Archibald Edward Garrod discovered this inborn genetic disease and proposed that if there is a mutation in a gene it will alter an enzyme in the pathway. This disease cause a urine to turn black because of the oxidation of homogenistic acid in the urine when expose to air. In addition, ochronosis (black pigments) in the joints, bones and schlera will appear due to deposition of homogenistic acid. In every case of genetic disease resulted from the phenylalanine metabolism, if accumulation of an intermediate that caused by a mutation in the pathway.

Article: Phenylalanine metabolism in uremic and normal man

Article: PKU mutation G46S is associated with increased aggregation and degradation of the phenylalanine hydroxylase enzyme.

Article: Alkaptonuria, ochronosis, and ochronotic arthropathy

=Website Sources=

Web Site #1: Classic Metabolomics
http://en.wikipedia.org/wiki/Metabolism#Investigation_and_manipulation

General Overview

 * The focus of this resource is specifically the description of Metabolism as a concept and partially the description of the classical methodology of investigating its function and predicting its actions normally and when perturbed. It describes the classic methods of investigating and quantifying metabolism as following a reductionist approach by focusing on single metabolic pathways or on minor interactions between several pathways. see picture) The methods used here often were the tracking of radioactive tracers through a pathway or the tracking of metabolic levels of certain key metabolites and biomarkers. Slightly newer pre Metabolomics methods included using genomic and proteomic data to apply holistic mathematical and statistic analysis to the metabolic systems overall. (see picture) These methods were still less effective than Metabolomics would presumably be.

New Terms

 * Reductionism: An approach to understanding the function and nature of a complex entity or process by reducing it to the interactions of its parts and subprocesses. Considered the main way to understand chemistry up until recently, new approaches within metabolomics and other systems biology fields have shown that reductionism is not effective for the needs of the biological sciences and applications of said sciences. wiki/Reductionism
 * Metabolic Network: The complete set of metabolic and physical processes that determine the physiological and biochemical properties of a cell. The entire metabolic network is closely related to the Metabolome. wiki/Metabolic_network
 * Radioactive Tracer: A radioactive molecule used to track the flow of molecules and atoms within a set of reactions. Can also be used to track biofluids. jhsmiami.org
 * Metabolic Pathway: A naming convention in biochemistry, the word pathway describes a collection of related chemical reactions that all happen in sequence moving from an arbitrary beginning point and afterwards to an arbitrary ending point. The pathway model is used to reduce the complexity of biochemical systems for easier analysis and teaching. Metabolic pathways are specifically biochemical pathways of the metabolome. (gleaned from context of the resource)
 * Molecular Dynamics: a form of computer simulation that attempts to model the motions and interactions of atoms and molecules under the known laws of physics. In the context of this resource it was one of the methods of classical biochemistry, using the reduced aspects of chemistry to try to model the whole. wiki/Molecular_dynamics

Course Relevance
 * This particular resource relates directly to the class since we continue to learn about biochemistry using the reductionist approach today. Biochemical pathways are a standard part of the learning of metabolic biochemistry and nearly everything we’ve done up to this date has been involved in learning and being tested on our knowledge of various important pathways in the metabolic networks of animal and plant cells.

Web Site #2: The Metabolomics Standards Initiative (MSI)
http://msi-workgroups.sourceforge.net/ The Metabolomics Standards Initiative

General Overview

 * The focus of this resource is to provide important information and establish standards for the Metabolomics field during its infancy and beyond. It has coordinated several workgroups together to detail the aims and standards of Metabolomics as a field and benefit other researchers working on similar projects.
 * Biological metadata workgroups are responsible for detailing the metadata of the experiments for Metabolomics and setting up the standards for running a Metabolomics experiment as detailed by the Metabolomics Society Metabolomics Society Webpage. The chemical analysis workgroup's job is to “identify, develop and disseminate best chemical analysis practices in all aspects of Metabolomics” CAWG. It's not their job to determine how experiments should be run but to establish a set of minimal standards to follow. The Data Processing workgroup concentrates on establishing standards for algorithms and data reporting DPWG and the Ontology workgroup will concentrate on making the language of Metabolomics coherent and understandable as well as relevant to the sciences OWG. The exchange format Workgroup concentrates on the exchange of information and the format of analysis. EFGW.
 * All of these workgroups represent the ongoing efforts to establish Metabolomics as a field in its own right. It shows that the old terminology and methodology of classic analytical biochemistry is simply not viable for the new Metabolomics field. The fact that a new set of terms, descriptions and ontology is needed shows just how far this field has gone from the traditional field.

New Terms

 * Ontology (information science): The representation of a set of concepts within a domain and the relationships between those concepts. wiki/Ontology_(information_science). In the context of this resource the domain is metabolic networks and the metabolome as well as the science of Metabolomics and the concepts contained within.
 * Data Processing : The conversion of raw data (usually through algorithms or analysis) into knowledge about a topic or concept. In the context of this resource, Data processing refers to the processing of data regarding metabolites and metabolic networks to yield knowledge about the function of biological systems and the effects of perturbations of them.
 * Metabolomics Society : A group of scientists and researchers dedicated to aiding the growth and development of the field of metabolomics as well as facilitating the cooperation between Metabolomics and other related fields.
 * Controlled Vocabularies (CV's) : Collection of terms and descriptions of concepts that are forced to follow specific rules or conventions to allow for maximum usefulness in the discourse about a field of study.
 * Disparate resources : Diverse or markedly different resources. This state in resources can often be a cause of problems for data communication since the differences in the resources make translation difficult. www.merriam-webster.com

Course Relevance
 * The description of the Biological Contexts and the Chemical analysis relates heavily to our class work as it describes the new base standards for metabolic investigation and deals with many of the biochemical pathways and aspects we have learned about.

Web Resource 3: The New Field of Metabolomics
http://en.wikipedia.org/wiki/Metabolite Wikipedia Article on Metabolomics

General Overview

 * The focus of this particular resource is a general overview of Metabolomics and the Metabolome. It describes the Metabolome and Metabolites as well as the study of them (Metabolomics itself) and then proceeds into giving a history of the new field. The webpage describes the analytical technologies used acquire data from the Metabolome and used to apply that data. It also went over many of the main applications that this field of study could be applied to.

 New Terms

 * Systems Biology : The new realm of biological study that concentrates on the systematic analysis of complex interactions in biological systems. This represents a move away from reductionism in biology towards the perspective of integration. Some scientists state that systems biology is not new but instead a return to the original workings of biology which put full stock on learning the overall system during its earlier times. wiki/Systems_biology
 * Metabolite : The products and intermediate materials of metabolic processes. wiki/Metabolite#Metabolites
 * Secondary Metabolite : Any organic compound that is not directly involved in the normal development, growth and/or reproduction of an organism. wiki/Secondary_metabolite
 * Hypercycles (chemical) : A self reproducing macromolecular system in which the RNAs and enzymes cooperate (see picture) The macromolecules also cooperate to provide primitive translation abilities which allows information to be translated into enzymes. pespmc1.vub.ac.be
 * Metabonomics : “The quantitative measurement of the dynamic multiparametric metabolic response of loving systems to pathophysiological stimul or genetic modification” wiki/Metabolite#Metabonomics
 * Nutrigenomics : The study of the relation between nutrition and genomics with the application of boosting and monitoring human health. wiki/Nutrigenomics

Course Relevance

 * Describes in some detail the workings of the metabolic systems of organisms and what is needed to understand them fully. Our class has dealt in the differences between Metabolomics and traditional metabolism as well as introductions to Metabolomics itself. This resource gives a very general but informative view of the material that we learned on our own for the first project on Metabolomics and expands off of it slightly. It also describes the Metabolome, which we have learned about piece by piece through pathways using the reductionist approach of classical biochemistry.

=Article Resources=

Article 1: New Methods of “-Omics”
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1197421#id2593737 Metabolic Engineering in the -omics Era: Elucidating and Modulating Regulatory Networks

General Overview
 * The focus of this article is to describe the impact of the expansion of traditional sciences into “–omics” a shorthand reference for a systems biology approach that expands from a single function or pathway (something like genetics or metabolism) into an integrated system model (like genomics and metabolomics). It goes over specifically the advances made in each field and how those advances serve to benefit metabolic engineering overall. The article first describes the nature of the situation giving background on what we know about regulation and the hierarchy of the regulation of metabolic processes (see picture) and then goes deeper into the contributions of proteomics, systems biology, genomics and finally metabolomics (see picture). They wrap up the article discussing how this will benefit metabolic engineering more than previous techniques.

New Terms

 * Metabolic engineering: The optimization of the regulatory and genetic processes in a cell in order to produce certain substances more efficiently and faster. The entire context of this article orientates around making this sort of thing easier and more effective. wiki/Metabolic_engineering
 * Proteolysis: The digestion of proteins by cellular enzymes or by other cellular means for a wide variety of purposes. This article cites it as one of the methods of phenotype regulation on the translation level of the hierarchy. wiki/Proteolysis
 * Holistic Approach: An approach that avoids the idea that the parts could yield an idea of what the whole would do and instead attempts to understand the function of the whole system. (gleaned from context in the article)
 * Hierarchical Metabolic Regulation: A set of theories that state that metabolic regulation operates in a hierarchy, that the genetic level is the first level, the protein translation level is the next level and the enzymatic regulation level is after that. It also states that complex interactions between level 2 and 3 often occur and blend the two together. (gleaned from context in the article)
 * Diauxic: Double growth. A description of the growth phases of a bacterial colony that is metabolizing a mixture of metabolites, usually sugars. wiki/Diauxie

Connection To Class
 * This article connects to Biochemistry: Metabolism mostly through its description of the Metabolomics portion and its focus on metabolic engineering. All of those things depend heavily on Metabolism and Metabolic knowledge. The article itself however is suggesting a move to the more systems orientated approach in Metabolomics (among other -omics) because the older methods of concentrating on single pathways and small scale integration simply does not give the knowledge necessary to achieve the aims that metabolic engineers wish to achieve. This relates to our Metabolomics projects and their contrast to the techniques and information we’ve learned that follows the more traditional approach of reduction of the systems to stand alone pathways with small levels of integration.

Article 2: Metabolomics and its new place in systems biology
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1626538 The Cinderella story of metabolic profiling: does metabolomics get to go to the functional genomics ball?

General Overview
 * This article focuses entirely on Metabolomics and whether it will be a scientific contender in the near future. It initially describes the history of Metabolomics and how it fits into the entire scheme of biological investigation and prediction for systems biology (see picture) as well as the past difficulties in working in this relatively new field. Because the numbers of metabolites that need to be kept track of at once are so high, the sciences have put more energy into proteomics and genomics previously. However the new techniques being used are high thorough put and cheap to use. Due to this Metabolomics has easily surpassed past Metabolism investigation methods and is beginning to surpass proteomics and genomics as well.
 * The article describes several major success stories for Metabolomics including comparisons of silent phenotypes in yeast, a high throughput diagnosis of coronary artery disease, and monitoring gene therapy in Duchenne Muscular Dystrophy among several others. These things in particular are in contrast to previous investigations of simple metabolism mostly due to their higher level of application. Metabolomics is simply capable of a far greater effect on the application of biochemistry than the original reductionist approaches of metabolism
 * The article also discusses the sheer volume of data that needs to be cataloged and measured before full effectiveness was reached and how cross correlations between Metabolomics and other “-omics” technologies can have major mutual benefits. For instance, Metabolomics is an effective rapid phenotyping tool for mutant tracking in genomics and can speed up the data acquisition in many genomics investigations as well as giving a more accurate view (see picture).
 * The article also discusses in slightly less detail the need for powerful databases and accounts for the fact that the technology and methods already exist to create and populate these data storage and manipulation tools. The article proceeded to point out the need for new and more powerful analysis technology due to the sheer amount of data that one needs to acquire. New Software is especially needed to manipulate and analyze the data as it comes in. The article concludes by stating the great potential Metabolomics has both in working with other “-omics” and in revolutionizing metabolic profiling but states that the Metabolomics needs to carefully consider a lot of different factors to get its foot in the door, especially in terms of metadata.

New Terms

 * Metadata: literally “data about data”. wiki/Metadata In the context of this article, Metabolomics metadata is the important side information about the metabolites, the profiles they interact within and their effects on the overall system. For Metabolomics the metadata could reach very high levels since the amount of variation and interconnected effects of changes within a metabolic profile can be astronomical.
 * Duchenne Muscular Dystrophy : Also referred to as DMD it is a form of muscular dystrophy caused by a mutation in the X chromosome related to the protein dystrophin. It causes decreasing muscle mass and progressive loss of muscle function in male children. wiki/Duchenne_muscular_dystrophy
 * Rapid Phenotyping : Phenotyping is generally a multiple tier process, requiring multiple tests, imaging and pathology to determine a phenotype of a specimen. hopkinsmedicine.org. Rapid phenotyping, using Metabolomics to generate a metabolic profile, is a high-speed method of generating the same resultant information that would normally take a battery of tiered tests and modeling. (gleaned from context in the article)
 * Co-resonant metabolites : In NMR spectroscopy nuclear magnetic resonance is used to detect certain chemicals. A co-resonant metabolite is specifically a metabolite whom has a resonance similar enough to other metabolites that detection and cataloging is difficult or even impossible using NMR. (gleaned from context of the article)
 * Toxicological insult : A metabolic event in which chemicals or metabolites themselves reach too high or too low of a level or interact with the metabolic system in some way that causes a toxicological effect on the system or part of the system. (context gleaned from article)

Course Relevance
 * This article deals very heavily in the chemical pathways that we’ve seen in class. During the discussion of how many metabolites needed to be measured the article discussed the structure and formation of various fatty acids and what effect that could have on the data needs of Metabolomics. It also discussed several side paths connected to pathways we’ve discussed in the success stories like tracking oxidative phosphorylation and sugar metabolism in yeast to find silent phenotypes.
 * It also discusses a lot of the new advances in Metabolomics, which directly relates to the previous project and how the new field of Metabolomics is growing.

Article 3: New drawing methods to represent changes in metabolic profiling
Metabolic network visualization eliminating node redundance and preserving metabolic pathways

General Overview
 * The focus of this article is describing the issues surrounding the previous metabolic profiling approaches that centered themselves on reductionism pathway analysis. It points out the shortcomings of attempts to draw genome scale metabolic networks using the typical pathway methods.
 * The article is a useful view into the methodology of traditional metabolism. For instance, it describes in the background how many biochemists would study one particular pathway, like glycolysis without taking into account other seemingly unrelated pathways that could interact with it. This article cited the usefulness of having large-scale representations of the metabolic profile and how it allowed a scientist to track perturbations of the metabolic system in multiple locations therefore boosting the efficiency and accuracy of metabolic investigation.
 * The article also discusses the issues with overlapping nodes and proposes a system in which concentration and focus of the metabolic profile and drawing may be chosen by the individual using it, to eliminate overlapping nodes but avoiding the loss of necessary data and context. They propose a software system using several algorithms to draw the metabolic maps in a more effective way. Several of these test maps are shown (see picture).
 * The article suggests using mixed bipartite graphs to model the data (see picture) and multi scale clustering in the drawing algorithm in order to help group together the drawing in a way that can be tracked visually and easily but not result in data loss. (see picture). The drawing method also draws metanodes to further enhance visualization with a recursive algorithm that draws the subgraphs from the most nested to the least nested. (see picture)
 * The article tested the software and methods and compared the drawing to other methodology tracking whether the drawing method was more or less accurate and whether it was easier or more difficult to read.

New Terms
 * Clustering: Data Clustering is the partitioning of a data set into subsets of clusters, so that the data in each cluster share a common trait. Proximity to each cluster is often used as a measure of relatedness. wiki/Data_clustering In the context of the article, clustering was used to determine which overlapping node would go where to prevent node repetition in each of the pathways represented.
 * Mixed Graph: A graph is a basic object of graph theory. It is a set of objects referred to as points, nodes or vertices (nodes for this article), which are linked by lines or edges (edges for this article) wiki/Mixed_graph. A mixed graph specifically is a graph in which some edges may be directed and some may be undirected, meaning that a node can be related to another node in a one-way relation or both can be related to one another. This was based on the context of metabolic reactions sometimes being reversible and other times not being reversible.
 * Bipartite graph: A graph in which the vertices can be divided into two disjoint sets such that every edge connects a vertex between the two sets (no edge between two vertices of the same set.) They tend to be useful for matching problems. wiki/Bipartite_graph. Within the scope of this paper, bipartite graphs were chosen because the nodes were not linked (this is because of no link between reactions themselves and no link between substrates themselves, which were the nodes in that example.)
 * Node (graph): Also referred to as a vertex, it is a fundamental unit for the formation of a graph. They are the objects in a graph, the edges imply relation between the nodes themselves. If two nodes are unrelated then there is no edge between them wiki/Vertex_graph_theory
 * Metabolic perturbation: Any event that causes a metabolic system to change from its normal functionality (gleaned from context in the article)
 * Recursion (recursive algorithm): A method of defining functions in which the function being defined is applied within its own definition. More generally it is a concept used to describe a process of repeating objects in a self-similar way. A good analogy is two parallel mirrors and the infinite nested images they show of each other. Recursive algorithms are simple but effective because of the concept of recursion and always require some form of base case (an end condition) that stops the recursion from going infinite. In the context of this article a recursive algorithm was used to boost the efficiency of the drawing technique. wiki/Recursion

Course Relevance
 * This article is so far the most divergent from our class studies because of its strong emphasis of statistical analysis, algorithms and drawing methodology. However it does have some strong connections to our class work primarily because its description of past methods resembles our own methodology for learning biochemistry in relation to metabolism.
 * The old methods of concentrating on single pathways or mild interaction between several pathways is the methodology with which we learn about the metabolic biochemistry. The reductionist approach has benefits for learning as it makes things smaller and easier to absorb for students who are still working their way up into an understanding of the concepts.
 * It also relates because most of our learning results from drawn diagrams that follow biochemical conventions for showing reactions and path integration. So it directly impacts the methods with which we learn biochemistry not just the material we have learned so far.


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title: The Science of Programming


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Metabolomics/Analytical Methods/NMR/H NMR

Back to Previous Chapter: Hormones Next chapter: Computational Modeling of Metabolic Control Next Category: Mass Spectrometry Go to: C NMR

Modern Application

Opium poppy is recognized as an ideal model for alkaloid plant metabolism study, because of its diverse array of bioactive benzylisoquinoline alkaloids. Cultivation of the plant has produced such commercial narcotic analgesics as morphine and codeine. Environmental stimuli are capable of impacting secondary plant metabolism, which is in turn capable of regulating other plant metabolic pathways. Researchers have employed proton nuclear magnetic resonance (1H NMR) metabolomics in order to investigate the interrelationship between primary and secondary metabolisms in opium poppy cells that had been treated with a fungal elicitor. Insight from this research is expected to reveal direct benefits of available opium alkaloids on the human metabolome.

Metabolite fingerprinting and compound-specific profiling revealed the extensive reprogramming of primary metabolic pathways that had been associated with alkaloid biosynthesis induction, in response to the elicitor treatment. The content of 42 diverse metabolites, in control and elicitor-treated opium poppy cell cultures, were monitored over timed 100 hour trials, with the use of a Chenomx NMR Suite v. 4.6 NMR spectrometer. Within five hours of the elicitor treatment, dynamic changes in elicitor-treated cell metabolomes were most significantly observed in the cellular pools of carbohydrates, organic acids and non-protein amino acids. Control cultures exhibited abundant fluctuations approximately 80 hours into the trials, and were most evident in amino acid and phospholipid pathway intermediate content. Overall, modulations were specifically detected in primary metabolic processes that produce secondary metabolic precursors. These modulations necessitated metabolite fluctuation in glycolysis, the tricarboxylic acid cycle, nitrogen assimilation, phospholipid/fatty acid synthesis and the shikimate pathway.

The comprehensive reprogramming of primary and secondary metabolism, along with associated cofactor biosynthetic pathways was mandatory for the analysis of cell culture responses to elicitor treatment. Ultimately, collected data produced a high-resolution map of this metabolic reprogramming, under specified conditions.

The Chenomx NMR Suite v. 4.6 spectrometer used for the experiment was “capable of identifying and quantifying individual compounds based on their respective signature spectra.” For the conducted experiments, samples were analyzed in D2O by 1H NMR. Employing NMR spectroscopy instead of mass spectroscopy (MS) for metabolomic analysis allowed for easier sample preparation, an analytical method that did not destroy sample analytes, and a more efficient and comprehensive compound identification method that provided structural descriptions of unknown compounds. The application of 1H NMR had also exposed a myriad of cellular metabolites that had not yet been observed, in previous research involving MS analysis.

Prospects

Opium poppy NMR Spectra:

http://www.biomedcentral.com/1471-2229/8/5/figure/F1

References:

http://www.biomedcentral.com/1471-2229/8/5

Overview: Nuclear Magnetic Resonance (NMR) is a powerful spectroscopic technique that gives information about both the structural and chemical properties of certain molecules. NMR is unique as it is one of the few non-destructive methods for analyzing structure and molecular dynamics. Proton NMR works by exploiting the behavior of H1 atoms when they are placed in a very strong magnetic field.

Basically, when a sample is placed in the magnet the nuclei of the proton atoms align with the magnetic field in a way analogous to when the needle of a compass aligns itself in the earth's magnetic field. The magnets used in NMR spectroscopy are ten thousand times stronger than the earth’s magnetic field. The NMR experiment consists of the application of radio frequency pulses of energy to the sample. These pulses stimulate the nuclei to rotate away from their equilibrium position and they start to rotate around the axis of the magnetic field. The exact frequency at which the nuclei rotate is related to both the chemical and physical environment of the atom in the molecule. So therefore, by using different combinations of pulses and delays it is possible to determine how each atom in the molecule interacts with other atoms in the molecule. Finally, using a large set of these interactions it is possible to calculate the three-dimensional structures of molecules. Nuclear Magnetic Resonance can also be used to look at dynamic processes. Some of which are internal motions within regions of larger molecules such as loops in a protein or the base pairs in DNA or RNA. NMR can also be used to monitor chemical reactions.

Image- http://www.pharmacy.arizona.edu/faculty/yanglab/images/NMRFacility/NMR.JPG

Links to any related materials in Wikipedia http://en.wikipedia.org/wiki/Proton_NMR

http://en.wikipedia.org/wiki/NMR

http://en.wikipedia.org/wiki/NMR_spectroscopy

Online source #1: http://riodb01.ibase.aist.go.jp/sdbs/cgi-bin/direct_frame_top.cgi

Spectrum database for compounds

This website is a database with the spectroscopy images for numerous organic compounds. It organizes the compounds into a integrated spectral data base system for organic compounds that allows anyone to use it as a references. The website holds not only proton NMR images but a wide range of other visualization techniques too. Its main purpose is to organize all the existing information on the spectra of organic compounds into a manageable system. By knowing a the molecular weight, molecular formula, compound name, or even the atoms present in the molecule, one can get a list of organic compounds whose spectra match that criteria.

Terms-

Organic compounds- Chemical compounds based on carbon chains or rings and also containing hydrogen, with or without oxygen, nitrogen, and other elements

Raman spectrum- a spectroscopic technique used in condensed matter physics and chemistry to study vibrational, rotational, and other low-frequency modes in a system

Electron spin resonance spectrum- technique for studying chemical species that have one or more unpaired electrons, such as organic and inorganic free radicals or inorganic complexes possessing a transition metal ion.

SDBS- (Spectral Data Base System) an integrated Spectral Data Base System for organic compounds.

Spectrometers- An optical instrument used to measure properties of light over a specific portion of the electromagnetic spectrum.

Spectral width- the wavelength interval over which the magnitude of all spectral components is larger than that of the component in question.

Connection-

This website relates to our biochemistry class because almost all the molecules that we were are studying are in this database. The molecules in our book and from the discussions in class were discovered or analyzed through proton NMR techniques. The spectra of these molecules are organized into one large database on this website.

Image- http://freebsd.kde.org/img/screenshots/en_jon-d_screen4.png

Online source #2: http://teaching.shu.ac.uk/hwb/chemistry/tutorials/molspec/nmr1.htm

Description of how proton NMR works

This web page gives an in depth analysis of how Nuclear Magnetic Resonance works and the theory behind it. The site goes on to explain how nuclear spin and the splitting of energy levels in a magnetic field affect the picture that is produced by NMR. It clarifies that the magnetic field, produced by the NMR apparatus, changes the spin and chemical shift of the nuclei of proton atoms resulting in different signals picked up by the machine. These signals, each of which are unique to a certain bond to hydrogen and the molecule in question, are presented to the user in the form of graph. The user can then interpret this graph to determine specific bonds and structure of molecule.

Terms-

Nuclear spin- an intrinsic property of certain nuclei that gives them an associated characteristic angular momentum and magnetic moment

Quantum mechanics- The laws of physics that apply on very small scales, eg to elementary particles and atoms.

Nucleus- the positively charged dense center of an atom

Spin relaxation- describes the interaction between neighboring nuclei with identical precessional frequencies but differing magnetic quantum states

Spin-spin coupling- Interactions between the nuclear spins of nearby nuclei, that give rise to characteristic splittings of resonance lines in NMR spectra.

Connections-

This website relates to the topics in class by demonstrating the science behind a tool that is used greatly in understanding biochemistry. Biochemists are constantly trying to identify new proteins and define biological processes such as the ones in our book. To understand them they need to be able to visualize the atoms of the molecules and reactions. To visualize them they will use either electron microscopes, NMR, or other techniques. Proton NMR is, by far, one of the easiest and most efficient ways to gain a quick understanding of the molecules in question.

Pictures-

http://pages.unibas.ch/mdpi/ecsoc-4/c0030/Image528.gif

http://www2.ups.edu/faculty/hanson/Spectroscopy/NMR/splittingtree.gif

Online Source #3:http://www.stolaf.edu/depts/chemistry/courses/toolkits/380/js/nmr1/

Database for proton chemical shifts

This website is a great database to view the chemical shifts of different aromatic compounds. The site allows you to manipulate different the frequency, the compound, and them functional group shown on the graph. This allows one to gain a general understanding of what to look for in chemical shifts of certain molecules and provide a standard for certain molecules and functional groups. This database can act as a reference for people who are trying to identify the metabolite or molecule in question.

Terms:

Functional group- a specific structure of one or more atoms that is responsible for the chemical behavior of a substance

Chemical shift- The difference between the resonance frequencies of a given nucleus and a standard reference nucleus

Peaks- The parts of the graph that give rise to the identification of splitting and are indicators of chemical structure.

Aromaticity- is a chemical property in which a conjugated ring of unsaturated bonds, lone pairs, or empty orbitals exhibit a stabilization stronger than would be expected by the stabilization of conjugation alone.

NMR resonant frequency- A variable on the apparatus that for a particular substance is directly proportional to the strength of the applied magnetic field.

Connections-

This website is related to the biochemistry class as it is a good visual of how biochemists determine the structure of compound they are trying to identify. As this web page focuses on aromatic compounds, it becomes pertinent to biochemists as both Phenylalanine, Tyrosine and Tryptophan, all have benzene rings. So if a biochemist were trying to identify metabolite in a metabolic pathway for the metabolomic database, he could refer to this site. If the proton NMR of his metabolite matches that of an aromatic amino acid, he would be able to narrow down his choices.

Images-

http://www.le.ac.uk/by/teach/biochemweb/images/aromatic.gif

http://hyperphysics.phy-astr.gsu.edu/hbase/organic/imgorg/aromatic2.gif

Article #1:http://www.ncbi.nlm.nih.gov/pubmed/18277383?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Applications of proton NMR

This article is a study of how proton NMR is now being used to measure subtle metabolic changes that precede and accompany chronic vascular complications. These complications are the primary cause of premature death due to diabetes. Scientists are using proton NMR, in their study, to obtain a multimetabolite characterization of high-risk diabetes patients. To do this they measured the serum of numerous patients with type I diabetes. With the use of the NMR they were able to develop new metabonomic frameworks to visualize and interpret the data and to link the metabolic profiles to the underlying diagnostic and biochemical variables.

Terms-

Macrovascular- Pertaining to the macrovasculature, the portion of the vasculature of the body comprising the larger vessels, those with an internal diameter of more than 100 microns

Serum- The noncellular liquid phase resulting from the clotting of a sample whole Blood or plasma

Metabonomics – The study of metabolic responses to drugs, environmental changes and diseases

Biomarkers - Substances in the blood whose levels can indicate the presence or extent of disease

Metabolic profile- An examination of a sample of blood to determine its chemical, physical, or serologic characteristics

Connections-

This article relates to the discussions in class by showing the applications of metabolomics and how it can be applied to diagnose and possibly treat disease. This study focused on diabetes in particular and used the close cousin of metabolomics, metabonomics, to determine how each different metabolite affects a metabolic pathway. Proton NMR helps by allowing scientists to view metabolites in diabetic patients’ blood both in vivo and in vitro easier. This ability to view the metabolites allows researchers to understand the effects of metabolites on pathways and helps to complete the metabolomic study of patients with diabetes.

Pictures

http://www.wired.com/ly/wired/news/images/full/ulderleg1_f.jpg

http://www.greenfacts.org/images/glossary/serum.jpg

Article #2:http://www3.interscience.wiley.com/cgi-bin/abstract/112149537/ABSTRACT?CRETRY=1&SRETRY=0

Use of Proton NMR to determine metabolic pathways

This article focuses on a new technique that harnesses water-suppressed localized proton NMR spectroscopy and stimulated echoes to detect metabolites in the human brain in vivo. This technique is able to apply proton NMR to an area of 64 square milliliters in order to view the molecules in the occipital area. The metabolites that they were able to view were acetate, N-acetyl aspartate, -amino butyrate, glutamine, glutamate, aspartate, creatine and phosphocreatine, choline-containing compounds, taurine, and inositols. Using this technology they were able to compare different metabolomic pathways to each other in vivo.

Terms-

Spectroscopy- Is the analysis of the lines of light emitted from excited atoms as the electrons drop back through their orbitals.

In vivo- In a living organism, as opposed to in vitro (in the laboratory).

Occipital area of the brain- the visual processing center of the mammalian brain, containing most of the anatomical region of the visual cortex.

MRI- a noninvasive, non-x-ray diagnostic technique based on the magnetic fields of hydrogen atoms in the body.

Spectra- The plural of spectrum. A range of wavelengths.

Connections-

This article ties in very well with past class discussions about metabolomics. It is at the root of the new science and reveals a how an already pre-existing tool can be used to aid in the human metabolomic project. By being able to view the intermediates and end products of the system pathways in vivo it becomes much easier to determine the effects of different metabolites on pathways. It does this by if one were to add a certain metabolite to a location in the body, proton NMR would allow us to see the how it effects the end product of the pathway without removing tissue.

Pictures-

http://cis.jhu.edu/data.sets/cortical_segmentation_validation/photos/occipital75.jpg

http://www.nature.com/npp/journal/v32/n6/images/1301248f1.jpg

Article #3:http://www.ncbi.nlm.nih.gov/pubmed/16648611?ordinalpos=10&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Applications of proton NMR

This article is a study a comprehensive compilation of a study done on mice, which utilized proton NMR as its primary visualization tool. The main objective of this study was to characterize the adipose tissue deposits and other visceral organs and to establish a model of in vivo phenotyping. The experiment used proton NMR to do a morphological analysis and create a 1H-NMR spectra focalized on specific lipid deposits. The results of the experiment showed that proton NMR could be used to great accuracy to measure the amount of the different types of lipid deposits in the body. Along with determining the different types of adipose (subcutaneous and visceral) they determined proton NMR allowed them to determine the amount of saturation and unsaturation of the triglycerides stored.

Terms-

Paradigm- an example serving as a model

Phenotype- The observable physical or biochemical traits of an organism, as determined by genetics and the environment.

Subcutaneous- beneath the skin

Visceral- Pertaining to the membranous covering of the internal organs

ob/ob Mice- a well-known animal model for obesity and diabetes.

Connections-

This article relates to what we have studied in class in many ways. The most obvious is lipid synthesis and metabolism, in which the study showed ways to view the gross break down and formation triglyceride deposits. If one used proton NMR before and after applying different stimulants and environments to the subject, one would be able to determine the amount of lipid metabolism occurring. Also by fixing the diet of the subject, we would be able to find the percent of lipid metabolism occurring in contrast to glycolysis.

Pictures-

http://www.hsph.harvard.edu/GSH-LAB/images/obese_mice.jpg

Peer-Reviewed Article #1:
Metabolomics as an Extension of Proteomic Analysis: Study of Acute Kidney Injury

Seminars in Nephrology, Volume 27, Issue 6, Pages 609-620 November 2007

Main Focus

 * Identify the main focus of the resource. Possible answers include specific organisms, database design, intergration of information, but there are many more possibilities as well.

New Terms

 * New Term 1: Definition. (source: http://)
 * New Term 2: Definition. (source: http://)
 * New Term 3: Definition. (source: http://)
 * New Term 4: Definition. (source: http://)
 * New Term 5: Definition. (source: http://)
 * New Term 6: Definition. (source: http://)
 * New Term 7: Definition. (source: http://)
 * New Term 8: Definition. (source: http://)
 * New Term 9: Definition. (source: http://)
 * New Term 10: Definition. (source: http://)

Summary

 * Enter your article summary here. Please note that the punctuation is critical at the start (and sometimes at the end) of each entry. It should be 300-500 words. What are the main points of the article? What questions were they trying to answer? Did they find a clear answer? If so, what was it? If not, what did they find or what ideas are in tension in their findings?

Relevance to a Traditional Metabolism Course

 * Enter a 100-150 word description of how the material in this article connects to a traditional metabolism course. Does the article relate to particular pathways (e.g., glycolysis, the citric acid cycle, steroid synthesis, etc.) or to regulatory mechanisms, energetics, location, integration of pathways? Does it talk about new analytical approaches or ideas? Does the article show connections to the human genome project (or other genome projects)?

Peer-Reviewed Article #2:
Metabolic Discrimination of Catharanthus roseus Leaves Infected by Phytoplasma Using 1H-NMR Spectroscopy and Multivariate Data Analysis

Plant Physiology 135:2398-2410 2004

Main Focus

 * Identify the main focus of the resource. Possible answers include specific organisms, database design, intergration of information, but there are many more possibilities as well.

New Terms

 * New Term 1: Definition. (source: http://)
 * New Term 2: Definition. (source: http://)
 * New Term 3: Definition. (source: http://)
 * New Term 4: Definition. (source: http://)
 * New Term 5: Definition. (source: http://)
 * New Term 6: Definition. (source: http://)
 * New Term 7: Definition. (source: http://)
 * New Term 8: Definition. (source: http://)
 * New Term 9: Definition. (source: http://)
 * New Term 10: Definition. (source: http://)

Summary

 * Enter your article summary here. Please note that the punctuation is critical at the start (and sometimes at the end) of each entry. It should be 300-500 words. What are the main points of the article? What questions were they trying to answer? Did they find a clear answer? If so, what was it? If not, what did they find or what ideas are in tension in their findings?

Relevance to a Traditional Metabolism Course

 * Enter a 100-150 word description of how the material in this article connects to a traditional metabolism course. Does the article relate to particular pathways (e.g., glycolysis, the citric acid cycle, steroid synthesis, etc.) or to regulatory mechanisms, energetics, location, integration of pathways? Does it talk about new analytical approaches or ideas? Does the article show connections to the human genome project (or other genome projects)?


text: User:Terra/message

title: User:Terra/message


text:
User:Matthias M.

de:Benutzer:Matthias M.

title: User:Matthias M.


text:
The Science of Programming/Introduction

A student of mine once remarked, after taking a programming languages class from me, that she had grown from a "syntax coder" to a Computer Scientist. She once knew only enough syntax to get a program to compile and to run, after a fashion, but now she can identify a computable problem, sort through a set of strategies for solving the problem, weigh their advantages and disadvantages, and implement the chosen strategy in a robust program.

I can take a little credit for this transformation, but I believe the honor should fall to the textbook I chose, SICP: "The Structure and Interpretation of Computer Programs" by Harold Abelson, Gerald Jay Sussman, and Julie Sussman. The Wizard Book, as it is affectionately known, is a wonderful text that challenges students to learn the nature of computation and data. An earlier edition of that very book lead me on that same journey from syntax coder to Computer Scientist. The book is so versatile it has been used as an introductory computer science text at some universities and as a programming languages text at others. In fact, I tell my students that if they were to be marooned on a desert island and they could take one computer science text, SICP should be their hands-down choice.

The existence of such a text as SICP is quite a deterrent to creating this textbook, but we have embarked upon such a task. If there are any drawbacks to SICP, they would be in the choice of Scheme as programming language to illustrates the concepts therein. While the authors justify their choice well, the use of Scheme has probably prevented a wider adoption of SICP as an text for introductory computer science courses.

This is not a fault of Scheme, which is an elegant, fun, and easy to learn language, but rather in the parochial view that students need to learn "practical" languages. These days, practical means the programming language C and the languages derived therefrom, C++ and Java, both of which add object-orientation while maintaining a C-like syntax. This trend towards object-orientation is the second, and perhaps more valid, criticism of Scheme and thereby the choice of SICP as an introductory text; Scheme lacks formal object-orientation. While there have been many attempts to add object-orientation to Scheme and LISP-like languages, the results have looked much like a Victorian home with a ranch-style addition - serviceable, but with jarring aesthetics.

The Sway Programming Language
The idea of the Sway programming language arose in this environment. I had been using a simplified C-like pseudocode in teaching an Algorithms class and my experiences teaching programming languages led me to believe I could implement a good portion of the pseudocode language. I chose the name Sway as I would often misspell pseudocode as psuedocode, which I reckon should be pronounced Sway-dough-code.

I designed Sway to have nearly the elegance of Scheme and all the fun, but with a C-like syntax to ease the transition of students from Sway to an industrial-strength language like C, C++, or Java. Moreover, Sway incorporates a fiendishly simple object and inheritance system based on a combination of previously published research in object orientation by others and my own research in this area. The idea that Sway should be fun makes the language a little more dangerous for novices. The point is: I wish to teach about computation and computational strategies rather than how to write a for loop in some toy language. To do so, the language of instruction needs to be expressive, the more expressive, the better. Also, I hope to avoid the pitfall of the Niklaus Wirth's Pascal programming language, a language, like Sway, designed for teaching. Wirth chose a rather rigid language model so that the language would be easier to learn. Under such a model, error messages generated by the language processor usually point out the error that led to the problem quite directly. Unfortunately, the language was inflexible and could not grow. This rigidness was responsible for Pascal falling, for the most part, by the wayside.

Sway is designed to grow in ways unanticipated by me and I have given Sway some properties that I believe give the language a solid base from which to grow. On the downside, this built-in flexibility can, at times, cause some rather obscure error messages. For example, a missing semicolon might generate a "missing expression" error message rather than the hoped for "missing semicolon" message. To make up for this trade-off, special care has been taken to make Sway monolingual. That is, the very same constructs for writing a program can be used to debug (fix errors). In fact, unlike most textbooks, this one provides a link to an entire chapter on the debugging of Sway programs, from the mundane (print expressions) to the sublime (running an interactive interpreter within a program).

Organization of the Book
This textbook is designed for students who would like a little practice in programming before moving on to a traditional CS1 class. The Science of Programming takes a non-traditional transit through the material, however. Rather than focusing on language features, the emphasis is on using a programming language to help the student understand material in an entirely different domain. In this case, the domain is Introductory Calculus. The student learns to program by writing short algorithms for solving Calculus problems. At the same time, students learn about Calculus and thus get a little practice in this subject before moving on to their first Calculus course.

In my mind, current CS1 textbooks suffer from a number of flaws. The first is that they tend to be encyclopedic. Thus many of the great concepts of computer science are obscured by a deluge of details. I don't, and I suspect many students do not, want to wade through an 800 page (or worse) textbook. Another flaw is that when examples are used to motivate language features, a detour is taken away from the example to introduce some new language construct, breaking up the narrative. Yet another flaw is that examples are usually contrived and not very convincing motivators for learning CS.

TSOP attempts to solve the first two flaws by taking advantage of the benefits offered by hosting the textbook online. When a particular language construct is needed to accomplish some task in TSOP, the reader is instructed to follow a link to learn about the construct, if desired. These links lead to sections in the Sway Reference Manual, a companion text to TSOP. These little pointers do not disturb the flow of the overall narrative. The final flaw is ameliorated by the use of examples (calculus) that are most certainly of benefit to a Computer Science major.

The chapters of TSOP follow exactly the text of Calculus Made Easy, by Sylvanus P. Thompson and updated by Martin Gardner. For a student who already knows Calculus, TSOP (with the Sway Reference Manual) stands by itself. For a student who wishes to learn calculus as well as programming, Calculus Made Easy is a necessary, and comforting, companion.

title: The Science of Programming/Introduction


text:
Trainz/Tutorials For Content Creation

 * 1) redirect Trainz/Reskinning Auran's Basic Traincar with Gmax<!--

Reskinning a Traincar Example
The example used here will take you through both reskinning and modifying the GMAX source of an existing model.

Six steps to reskinning

 * You need to do six things in general to reskin an rolling stock asset
 * first clone the item and the texture group
 * second point the item to the new texture group
 * third do the reskin
 * fourth reskin the texture group
 * fifth adjust the wagon number position
 * finally do the s.

It takes me about ten minutes once the reskin is done.

It one relies heavily on textures rather than the shape of the mesh for its effect. All the textures are in one file which is good for performance and it has. It is also scripted for couplings, Chameleon for the wagon numbers and is capable of using vacuum pipes. The texture file is modified from one created by Paul Hobbs. The GMAX source and some alternative tga files are included in wagonzip.txt, just change the file extension to zip and unzip it, this allows you to make modifications to the wagon or adjust the position and size of the wagon numbers.

Acquire the asset
First step is to download <kuid 86627:1654> with its 'texture group' <kuid 86627:1657> from the DLS.
 * CSL: <kuid 86627:1654>,<kuid 86627:1657>

Clone the asset
Then if using we clone the item in CMP. Another method if PEVtools are in your toolkit is to open the asset for edit using PEV's Images2TGA and copy that file to another locale on your HDDs. Revert the original. Note, CM also has a clone capability in the menuing.

Open the Clone in Windows Explorer
Now we open the file in edit in explorer.

In this example we can see a number of folders and ''by convention (back to the original Content Creator's Guide and the original folder organization in Trainz 0.9/1.0–2.4), we are interested in the '_body folder'.

We can see a number of .tga files and generally speaking we are interested in the largest one, cs_skin.tga. Note that this particular model as a couple of alternative cs_skin.tga files that have had their colours changed in a recent version of PaintShop Pro are available in the wagonzip.txt file in the parent folder. To use them overwrite the cs_skin.tga with the appropriate one. N.B. Do not unzip this file without copying it out of Trainz first or CMP will get upset.

There are two other associated files with similar names in this example cs_skin_med.tga, and cs_skin_low.tga which are used by the two lower level lod.im files.

When we edit the file notice the two different sides and ends. Also note the two squares in the top right that are used to colour parts of the buffers, if you are changing the colour then these must be changed also.

If you open the cs_skin_reskin.tga in the zip file you can see the sizes of these sides and ends. For a photo reskin simply resize the side photo and end photos to these sizes and position them appropriately. You will still need to change the colour of the two squares in the top right corner.

To change the colour of the wagon in Paintshop Pro Xi or later use the colour changer tool.

To add lettering use the letter tool seen here adding white lettering to the grey version of the cs_skin.tga file.

There are two other associated files with similar names in this example cs_skin_med.tga, and cs_skin_low.tga which are used by the two lower level lod.im files. When you have finished your reskin resize the image by 50% and 50% to make the med then once again to make the low versions for the lod meshes.

This gives you the basic reskin. This particular reskin uses changeable wagon numbers. If they stay in the same place we just need to reskin the numbers, if they need to be moved we will need to invoke GMAX. To reskin the wagon numbers we edit the files in the texture group or kuid 86627:1657. The wagon numbers themselves are on a plane roughly one tenth of an inch above the model and this plane uses a separate texture file called in this case ssa.tga.

The following example uses the texture files from a US Army boxcar to illustrate this found in "25647 ssa.tga" in the zip file. Note the files ssa1.tga through ssa15.tga are used by Chameleon wherever ssa.tga is referenced. So since we textured the wagon number with ssa.txt Chameleon replaces the wagon number texture with the appropriate ssa?.tga.

One difficulty with wagon numbers is matching the typeface used so one technique is to crop them number off a photograph and then edit that to give a set of wagon numbers. When we crop use the largest initial photograph available and if possible crop on a power of two so resizing is not required. 64 pixels by 16 pixels etc. The planes can always be resized so that the cropped image matches the wagon.

The first step is to copy the crop to a new image.

Then paste a new copy twice to give us two images to play with.

Next we cut a single digit out using the crop tool.

Copy this, then activate the ssa1.tga image by clicking on the blue stripe above and paste as a new layer.

Now use the move tool (1) to position the digit where we want it to be (2).

Finally we save the edited file using save as.

Repeat the process to create ssa2.tga, ssa3.tga etc. each with a different number.

Moving the wagon numbers will be covered in the GMAX part.

To upload to the DLS see the section on uploading.

title: Trainz/Tutorials For Content Creation


text:
The Sway Reference Manual/Starting Up

A word of warning: if you require fancy graphically oriented development environments, you will be sorely disappointed in the Sway Programming System. Sway is programming at its simplest: a prompt at which you type in expressions which the Sway interpreter evaluates. Of course, you can create Sway programs using your favorite text editor (mine is vim). Sway can be used as a scripting language, as well.

Installing Sway
Procedures for downloading and installing Sway can be found at http://sway.cs.ua.edu.

Running Sway
In a terminal window (DOS box on MS Windows), simply type the command:

sway

and press the  key. You should be rewarded with the Sway prompt.

sway>

title: The Sway Reference Manual/Starting Up


text:
User talk:Terra/archivemessage

This is Terra's Archives DO NOT EDIT THESE!

 * If you wish to re-open a discussion please do so via click here to start a new discussion, which will automatically be at the bottom of my Official Talkpage I will respond to comments there.

To Re-Open a previous Discussion

title: User talk:Terra/archivemessage


title: File:Ssa1.jpg


text:
User talk:64.162.43.183

February 2008
Terra What do you want? 19:44, 26 February 2008 (UTC)

title: User talk:64.162.43.183


title: File:Ssa2.jpg


text:
Blender 3D: Noob to Pro/Understanding the Fluid Simulator

Understanding the Fluid Simulator
When I first encountered the Fluid Simulator I had a hard time understanding its behavior, especially the Start time and End time didn't seem to make any sense at all. Going on a Google spree revealed that many people have problems figuring out the secrets behind fluid simulation, and I didn't find any truly helpful guides. In this little guide I'll try to explain it in a newbie friendly way. It may not be entirely correct, although it might help newbies understanding how it works.

First of all
Start time and End time are in seconds. Don't forget this. Even if your simulation seems to go insanely fast when you set Start time to 0 and End time to 10 and having 250 frames in your animation with 25 frames per second, there is a good reason for this. For now, just remember this, don't let your mind wander and believe that the values are in milliseconds or that you have to do some wicked math dividing/multiplying with frames and so on.

Also notice that the domain is the bounding box for the whole fluid calculation. EVERYTHING is done inside this box. It acts as the floor, ceiling and walls for all of the fluid. This is very important, as the number 1 reason why I couldn't get a good fluid simulation going. If I have time, I will do a section on Fluid > Control, but for now, I will say that it adds a LOT of calculation time. Running on an I7, ATI Radeon 8970 Video, Asus P6X58D Premium, 64-bit Windows 7 and 64-bit Blender, I crashed my computer with the lowest quality settings. So just remember that the domain MUST surround the area in which you do calculations. Also note that after you set up your simulation, the domain becomes the actual liquid, so give it proper material and try not to bake until you're pretty sure of your simulation.

Setting up the scene
We'll learn how the fluid works the practical way. plane

 * Start with the default box, this simulation will be very simple.
 * Let's work in wireframe mode, press the ZKEY to turn off solid mode.
 * Go in to camera view by pressing Numpad0.
 * With the box selected, scale it up to two times by pressing SKEY, then 2, then ENTER. This fits the camera fairly well.
 * Press Numpad7 for a top view.
 * With the box selected, press Shift-D (don't move the mouse or else the duplicated box will move) then press ENTER to confirm the duplicated box's location. If you do move the box, just press Escape then the new box will be kept but the move cancelled.
 * While the new box is selected (and in exactly the same spot as the other box), press SKEY, then .5, then ENTER to scale it to half size.
 * Stay away from the mouse, accuracy is important here and I'll explain why later.
 * Now we want to move the new box into one of the upper corners. Press the GKEY, then press the XKEY, type in -1, press ENTER and the box should move to the left wall of our larger box.
 * We want the box in a corner, so press GKEY Y 1 Enter, the box should now be in the top left corner from our current view.
 * However, we're in 3 dimensions, not 2 so click Numpad1 for a side view. This time we'll move the box up along the Z-axis: G Z 1 Enter.
 * Excellent, our setup is done.

Setting up the simulation

 * Make sure you're in Object Mode, and that you followed the above steps precisely.
 * Select the smaller box and click F7 twice. You should get a panel where the rightmost pane says "Fluid Simulation". Click Enable.
 * Our small box will be the fluid, so just click the Fluid button. That's all there is to do with the small box.
 * Now select the large box. The Physics panel should still be visible, click Enable in the Fluid Simulation pane and then select Domain.
 * By default your animation should have 250 frames. Rendering should also be set to 25 frames per second by default, this tutorial assumes this setup.
 * Since we got 250 frames and 25 frames per second that means our animation is 10 seconds long. So here comes the tricky part, which actually isn't that tricky at all:
 * Start time is by default set to 0 seconds. This means that on the very first frame the simulation has just begun. You could increase this value to say, 1 second and that would mean that on the first frame the fluid simulation has already run for 1 second. We don't want to do this, so keep it at 0 seconds.
 * End time is by default set to 0.3 seconds. What does this mean? This means that on the 250th frame the simulation has run for 0.3 seconds. However, by default our animation is 250 frames long with 25 frames per second, making those 0.3 seconds stretched over 10 seconds. Basically this means that we're watching the show in slow motion, or slightly less than 1/33 the realtime speed. So now you may think "it looks quite realtime to me!", and yes, it does, but why does it do that? Well, that's hard to explain. Consider this: In a world without friction, how far would a drop of water fall after 1 second? The answer is about 4.9 meters. So, if a drop of water falls from 4.9 meters it will take 1 second before it reach the ground. How long would it take the waterdrop to reach the ground if it falls from 3 centimeters? About 0.078 seconds. So why do i mention 3 centimeters? Because by default the size of our domain is 3x3x3 centimeters, or really small. If you're like me, you were probably thinking that the fluid was flowing around in a bathtub or a barrel, not in the wrapping of a cupcake. Set End time to 10 seconds.
 * Since our imagination likes big things, let's crank up that cupcake to say, a swimming pool. Make sure the big box is selected in Object Mode In and look at the Fluid Simulation pane. Just to the left of the "BAKE" button there should be 3 other buttons, possibly named "St", "A", "B". Click A for advanced options.
 * Some new boxes should appear, Gravity (should be -9.81 for the Z-axis, nothing else), Water and the option we're looking for, "Realworld-size". Also Gridlevels and Compressibility, but let's not care about those now.
 * The "Realworld-size" value says how large our domain is in meters, and as you can see it's 0.03 meters by default, or 3 centimeters. We want it huge, so crank it up to 10, which is the limit for Blender 2.45. Now our swimming pool is 10x10x10 meters (don't drown!), remember this because scale matters with fluid. Do not think we're playing with cupcakes again :)
 * Now click BAKE, and read on while your computer is chewing zeroes and ones.
 * Remember how I told you to be very accurate about placing that second box? And how I began talking about gravity, falling waterdrops and stuff? Well, now you're going to see why.
 * As stated, our "swimming pool" is 10x10x10 meters. The smaller box we added is exactly half the size (well, in terms of length/width/height, not volume), or 5x5x5 meters. Remember that a drop of water would fall 4.9 meters in 1 second? And that our animation got 25 frames per second? This means that the bottommost part of our blob of water will be exactly 5 meters above the "ground", and that after 25 frames our water should be very close to the ground.
 * If you got a fast computer, Blender should be done baking by now. Go to frame 25, for example by using the arrow keys (up/down goes 10 frames forwards/backwards, right/left goes 1 frame forward/backward). Take a close look at the blob, then go forward 1 frame. Notice how the blob hits the ground? Rings a bell, doesn't it? :)
 * Although, we're not done! We gotta render our swimming pool. It's easy, but takes time, hit Ctrl-F12 and go make dinner.
 * When the rendering is done, press Ctrl-F11, and think of a 10x10 meter large pool. You might want to keep an eye on your kids if your local swimming pool acts this way, though.

Final notes
Scale matters. It's really difficult to understand fluid dynamics on a very small scale, especially when you don't even know what scale is used. The "Realworld-size" value seems to be left out in many guides, I would recommend you set it to something you can relate to, or you'll end up with simulations that look really slow/fast or having an End time value that seemingly makes no sense. Further I'm not a mathematical genius, for all I know I could be way off with my explanation, although this way the values makes sense to me, and I'm able to make fluid simulations without "guessing" on values for End time.

Extra Practice
This YouTube tutorial on fluids might also help: Link and this Realistic Water Texture

Links

 * Youtube: Comparison of different values for resolution and real-world size


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text:
Metabolomics/Hormones

Back to Previous Chapter: Metabolites Next chapter: Analytical Methods

=Hormones=

Hormones are defined as chemical signals that affect one or more cells in an organism. Hormones can have an amplification effect where a small signal causes a large response.

Table of Contents

 * 1) Insulin
 * 2) Glucagon
 * 3) Somatostatin
 * 4) Corticosteroids
 * 5) Mineralocorticoids
 * 6) Leptin
 * 7) Adiponectin
 * 8) Ghrelin

title: Metabolomics/Hormones


text:
The Sway Reference Manual/Primitives

Sway works by figuring out the meaning or value of some code. This is true for the tiniest pieces of code to the largest programs. The process of finding out the meaning of code is known as evaluation.

The things whose values are the things themselves are known as primitives. The primitives of Sway can be categorized by the following types: integers, real numbers, strings, and symbols.

Sway (or more correctly, the Sway interpreter) responds to primitives by giving the type of the value plus the value itself.

Here are examples of each of the types:

sway> 3 INTEGER: 3 sway> -4.9 REAL_NUMBER: -4.9 sway> "hello" STRING: "hello" sway> :age SYMBOL: :age

Let's examine the four types in more detail.

Integers
Integers are numbers without any fractional parts. Examples of integers are:

sway> 3; INTEGER: 3 sway> -5; INTEGER: -5 sway> 0; INTEGER: 0

Integers must begin with a digit or a minus sign. The initial minus sign must immediately be followed by a digit.

Real Numbers
Reals are numbers that do have a fractional part (even if that fractional part is zero!). Examples of real numbers are:

sway> 3.2; REAL: 3.20000000000 sway> 4.0; REAL: 4.00000000000 sway> 5.; REAL: 5.00000000000 sway> 0.3; REAL: 0.30000000000 sway> .3; REAL: 0.30000000000 sway> 3.0e-4; REAL: 0.00030000000 sway> 3.0e4; REAL: 30000.0000000 sway> .000000987654321 REAL: 9.8765432e-07

Real numbers must start with a digit or a minus sign or a decimal point. An initial minus sign must immediately be followed by a digit or a decimal point. An initial decimal point must immediately be followed by a digit. Sway accepts real numbers in scientific notation. For example, $$3.0 * 10^{-11}$$ would be entered as 3.0e-11. The 'e' stands for exponent and the 10 is understood, so e-11 means multiply whatever precedes the e by $$10^{-11}$$.

The Sway interpreter only displays between six and eleven significant digits, depending on the size of the number, so 1.234567898765432 would display as:

sway> 1.234567898765432; REAL: 1.2345678988

Don't be fooled. Although the result looks like 1.2345678988, it is not. The following code tests if the two numbers are equal:

sway> 1.234567898765432 == 1.2345678988; SYMBOL: :false

Numbers greater than $$10^6$$ and less than $$10^{-6}$$ are displayed in scientific notation.

To display more (or less) significant digits, the fmt function can be found. Here's how to display 15 digits after the decimal point:

sway> fmt("%.15f",1.234567898765432); STRING: 1.234567898765432

The fmt function uses the same format codes as the C printf function.

Don't try and display more than 16 significant digits; the least significant digits will not be accurate.

Strings
Strings are sequences of characters delineated by double quotation marks:

sway> "hello, world!"; STRING: "hello, world!" sway> "x\nx"; STRING: "x\nx" sway> "\"z\""; STRING: "\"z\"" sway> ""; STRING: ""

Characters in a string can be escaped with the backslash character, which changes the meaning of some characters. For example, the character 'n', in a string refers to the letter 'n' while the character sequence '\n' refers to the newline character. A backslash also changes the meaning of the letter 't', converting it into a tab character '\t'. When other characters are escaped, their meanings are not changed. Thus '\z' is equivalent to 'z'. To include a backslash character in a string, escaped it with a backslash, '\\'. Note that Sway, when asked the value of strings that contain newline and tab characters, displays them as escaped characters. When newline and tab characters in a string are printed in a program, however, they are displayed as actual newline and tab characters, respectively. Double quotes can be embedded in a string by escaping them with backslashes. A string with no characters between the double quotes is known as an empty string.

Unlike some languages, there is no character type in Sway. A single character 'a', for example, is entered as the string "a".

Symbols
Sway symbols are collections of certain characters beginning with a colon:

sway> :abc; SYMBOL: :abc sway> :a+b; SYMBOL: :a+b

When symbols are printed in a program, the colon is omitted from the output. Symbols may contain any of the printable characters except parentheses, braces, semicolons, and commas. The colon marks the beginning of the symbol while whitespace (newlines, tabs, and spaces) and the prohibited characters signal the end of the symbol. As we shall see later, symbols are useful for setting up symbolic constants and for passing messages.

There are a few special symbols in Sway, two of which are :true and :false. These symbols are known as the Boolean values and are used to guide the flow of a program. The term Boolean is derived from the last name of George Boole, who, in his 1854 paper "An Investigation of the Laws of Thought, on which are founded the Mathematical Theories of Logic and Probabilities", laid one of the cornerstones of the modern digital computer. The so-called Boolean logic or Boolean algebra is concerned with the rules of combining truth values (i.e., true or false). As we will see, knowledge of such rules will be important for making Sway programs behave properly. In particular, Boolean expressions will be used to control conditionals and loops.

Another special symbol is :null. This symbol is used to indicate the end of lists and arrays; it also indicates an 'not yet created' object.,

title: The Sway Reference Manual/Primitives


text:
Permaculture Design

Foreword
This Wikibook is, of course, a collaborative research project. It's currently in its early stages. If there are dead links, you are encouraged to fill them in. Feel free to use the discussion tab at the top of this page to discuss this and any other topic in the book. Use the |discussion page to discuss anything from format and content to objectives and style, and respectfully edit and add where needed.

Introduction
Permaculture has its origins in the designs of produce gardens, farms, houses and communities, and so the examples and references in texts are dominated by such. It is hoped that over time, this text will collect references and examples of permaculture design processes being applied in a wider range of contexts.

This book aims to provide a theoretical overview of permaculture to serve as a starting point for the research and application thereof. It does not aim to serve as an encyclopedia as there are other resources for that (see Other Resources).

Contents

 * Ethics, principles, methods and outcomes
 * /Fundamentals/ - another approach to ethics and principles
 * /Yield/
 * Observation
 * Characteristics
 * /Soil/
 * /Animals/
 * Base Map and sector analysis
 * Designer's checklist
 * /Zone design/
 * /Permaculture elements/
 * /Needs and yields analysis/
 * /Financial permaculture/
 * /Edible plants Classification and Care/
 * How to:
 * Some ways to improve your soils
 * Effective but non toxic sprays
 * Creating a natural balance
 * Planting Calendars
 * Seed balls

 * /References/

Related books

 * Hydroculture
 * Drinking water

Other Resources

 * PermaBlitz
 * Offsite Permaculture Wiki Database Permaculture.info

title: Permaculture Design


text:
Permaculture Design/Ethics, principles, methods and outcomes

Collaborative research project. Feel free to use the discussion tab at the top of this page to discuss this topic. Use the resources from the Permaculture design course, and conduct your own research and add summarised notes here to produce a useful quick reference page for others.

''Permaculture contains ethics that lead to principles. Some of the ethics overlap the principles. The principles lead to methods. The principles and the methods overlap each-other. The methods lead to outcomes. The outcomes overlap everything because it works like the our cells work in our body. It is a self regulating perpetual cycle, and we are part of it. There is no "one solution." To me, permaculture is the synergy of all elements.'' Capt Benny Pants, an online participant in the Permaculture Design Course 2008.

=Ethics=
 * Earthcare – recognising that the Earth is the source of all life (and is possibly itself a living entity- see Gaia theory) and that we recognise and respect that the Earth is our valuable home and we are a part of the Earth, not apart from it.
 * For example:
 * Conservation of Biodiversity
 * Clean air and water
 * Restoration and conservation of forests, habitats and soils
 * Recycling and pollution reduction
 * Conservation of energy and natural resources
 * Appropriate technology

 * Peoplecare – supporting and helping each other to change to ways of living that are not harming ourselves or the planet, and to develop healthy societies.
 * For example
 * Health and well-being
 * Nourishment with good food
 * Lifelong learning
 * Right livelihood and meaningful work
 * Community belonging
 * Open Communication
 * Trust and Respect

 * Fairshare (or placing limits on consumption) - ensuring that the Earth's limited resources are utilised in ways that are equitable and wise. Also if a wall retains heat, pass on the heat to a plant that needs it; if a plant provides shelter, place it on a wall that needs cooling.
 * For example
 * Co-operation
 * Networking and sharing
 * Distribution of resources and wealth
 * Reduction of consumerism
 * Rethinking current notions of growth, progress and development
 * Making a contribution

=Principles= These restatements of the principles of permaculture appear in David Holmgren's Permaculture: [Principles and Pathways Beyond Sustainability http://www.holmgren.com.au]; Also see permacultureprinciples.com;

 * 1) Observe and interact - By taking the time to engage with nature we can design solutions that suit our particular situation.
 * 2) Catch and store energy - By developing systems that collect resources when they are abundant, we can use them in times of need.
 * 3) Obtain a yield - Ensure that you are getting truly useful rewards as part of the work that you are doing.
 * 4) Apply self-regulation and accept feedback - We need to discourage inappropriate activity to ensure that systems can continue to function well.
 * 5) Use and value renewable resources and services - Make the best use of natures abundance to reduce our consumptive behaviour and dependence on non-renewable resources.
 * 6) Produce no waste - By valuing and making use of all the resources that are available to us, nothing goes to waste.
 * 7) Design from patterns to details - By stepping back, we can observe patterns in nature and society. These can form the backbone of our designs, with the details filled in as we go.
 * 8) Integrate rather than segregate - By putting the right things in the right place, relationships develop between those things and they work together to support each other.
 * 9) Use small and slow solutions - Small and slow systems are easier to maintain than big ones, making better use of local resources and produce more sustainable outcomes.
 * 10) Use and value diversity - Diversity reduces vulnerability to a variety of threats and takes advantage of the unique nature of the environment in which it resides.
 * 11) Use edges and value the marginal - The interface between things is where the most interesting events take place. These are often the most valuable, diverse and productive elements in the system.
 * 12) Creatively use and respond to change - We can have a positive impact on inevitable change by carefully observing, and then intervening at the right time.

Methods
There can be any number of methods for designing permaculture. The methods you develop should be informed by the ethics and principles above.

Outcomes
Outcomes are the things that result from the methods. Outcomes should be accountable to the ethics and principles, and if they deviate, either the method must be reviewed, or the ethics and principles adjusted.

=References=
 * Wikipedia Feb 2008
 * Wikibooks 2008
 * Video: Earth Care by Astral Jester that introduces the principles and ethics of Permaculture.
 * Seed International


text: User talk:205.125.173.31

title: User talk:205.125.173.31


text: User talk:82.101.129.107

title: User talk:82.101.129.107


text:
Khepera III Toolbox/The Toolbox/Modules/measurement

The measurement module provides a common framework for all programs which solely read a sensor (or several sensors) and report the result. Programs using this module therefore accept the same command line options to specify
 * the interval between two measurements (-w US)
 * the number of measurements to be taken (-r N or just -r for continuous measurements)
 * whether to print the results
 * right after measuring (default)
 * at the end (-f)
 * not at all (-F)

Synopsis
Check out the source code of the battery program for an example.

Description
This module controls the main program flow and requires only two hook functions: Furthermore, an array for storing intermediate measurement must be provided.
 * A hook function take one measurement (hook_measure)
 * A hook function to print one measurement (hook_print)


text: User talk:204.193.6.90

title: User talk:204.193.6.90


text:
The Sway Reference Manual/Precedence and Associativity

Precedence
Precedence (partially) describes the order in which operators, in an expression involving different operators, are evaluated. In Sway, the expression

3 + 4 < 10 - 2

evaluates to true. In particular, 3 + 4 and 10 - 2 are evaluated before the <, yielding 7 < 8, which is indeed true. This implies that + and - have higher precedence than <. If < had higher precedence, then <tt>4 < 10</tt> would be evaluated first, yielding <tt>3 + true - 2</tt>, which is nonsensical.

Note that precedence is only a partial ordering. We cannot tell, for example whether <tt>3 + 4</tt> is evaluated before the <tt>10 - 2</tt>, or vice versa. Upon close examination, we see that it does not matter which is performed first as long as both are performed before the expression involving <tt><</tt> is evaluated. It is common to assume that the left operand is evaluated before the right operand. For the logical connectives, this is indeed true. But for other operators, such an assumption can lead you into trouble. You will learn why later. For now, remember never, never, never depend on the order in which operands are evaluated!

The lowest precedence operator in Sway is the assignment operator which is described later. Next come the Boolean connectives && and ||. At the next higher level are the Boolean comparatives, <, <=, >, >=, ==, and !=. After that come the arithmetic operators +, -, *, /, and %. Finally, at the highest level of precedence is the selection, or dot operator (the dot operator is a period or full-stop). Higher precedence operations are performed before lower precedence operations. Functions which are called with operator syntax have the same precedence level as the mathematical operators.

Unlike the algebraic precedence you learned in grammar school, multiplication and division are at the same precedence level as addition and subtraction in Sway. Thus, in combinations of these operators, operations to the left are performed before operations to the right. To force multiplication and division to be performed prior to addition and subtraction, parentheses must be used. For example:

sway> 5 + 2 * 3   //5 plus 2 is 7, 7 times 3 is 21 INTEGER: 21

but:

sway> 5 + (2 * 3) //2 * 3 is 6, 5 + 6 is 11 INTEGER: 11

Associativity
Associativity describes how multiple expressions connected by operators at the same precedence level are evaluated. All the operators, with the exception of the assignment operator, are left associative. For example the expression 5 - 4 - 3 - 2 - 1 is equivalent to ((((5 - 4) - 3) - 2) - 1). For a left-associative structure, the equivalent, fully parenthesized, structure has open parentheses piling up on the left. If the minus operator was right associative, the equivalent expression would be (5 - (4 - (3 - (2 - 1)))), with the close parentheses piling up on the right. For a commutative operator, it does not matter whether it is left associative or right associative. Subtraction, however, is not commutative, so associativity does matter. For the given expression, the left associative evaluation is -5. If minus were right associative, the evaluation would be 3. The only operator that is right associate is the assignment operator. You will see why in the assignment chapter.


text: User talk:86.20.130.14

title: User talk:86.20.130.14


text:
Khepera III Toolbox/The Toolbox/Modules/nmea

The nmea module parses a stream of NMEA 0183 messages.

Description
nmea_parser_init initializes a new NMEA parser. After initialization, the following hook functions can be set in the parser structure:
 * hook_process_message: Called whenever a complete and correct message is received.
 * hook_process_message_checksum_error: Called whenever a complete message with a wrong checksum is received. Such messages should be discarded.
 * hook_process_unrecognized_char: Called whenever a char which does not belong to a message is received.

Data must then be passed to nmea_parser_process_data, which parses the stream and calls the appropriate hook function.

Sending NMEA Messages
Sending NMEA messages is usually done by printing the corresponding values directly with printf. However, there may be situations in which you want to send an NMEA message structure as correctly formatted NMEA message. This is done as follows:


text:
User talk:81.151.204.137

Az1568(Talk) 21:46, 26 February 2008 (UTC)

title: User talk:81.151.204.137