O'Really?

February 12, 2010

The 3rd OBO Foundry Workshop 2010, Cambridge, UK

Ultrawide Wellcome Trust Genome Campus, Cambridge by Tim NugentThe Open Biomedical Ontologies (OBO) [1] are a set of reference ontologies for describing all kinds of biomedical data shared in a centralised repository called The OBO Foundry. Every year, users and developers of these ontologies gather from around the globe for a workshop at the EBI near Cambridge, UK. Following on from the first workshop two years ago, the second workshop last year it’s already time for the third workshop on February 15th-16th. All the details and agenda are here if you’re interested. This workshop is possible thanks to sponsorship from the BBSRC funds for Workshop on Data Standards and the EU ELIXIR ‘Data Integration & Interoperability’ Package 7.

[Update: outcomes from the workshop are available here, along with a summary of discussion from Monday and a summary of discussion from Tuesday.]

References

  1. Smith, B., Ashburner, M., Rosse, C., Bard, J., Bug, W., Ceusters, W., Goldberg, L., Eilbeck, K., Ireland, A., Mungall, C., Leontis, N., Rocca-Serra, P., Ruttenberg, A., Sansone, S., Scheuermann, R., Shah, N., Whetzel, P., & Lewis, S. (2007). The OBO Foundry: coordinated evolution of ontologies to support biomedical data integration Nature Biotechnology, 25 (11), 1251-1255 DOI: 10.1038/nbt1346

[Ultrawide panoramic picture of the Wellcome Trust Genome Campus by Tim Nugent, as featured on the cover of the EMBL-EBI Annual Scientific Report 2009. Making those pictures looks like a lot of fun.]

February 5, 2010

Classic paper: Montagues and Capulets in Science

Romeo and Juliet by HappyHippoSnacksIn preparation for a joint seminar I’ll be doing with Midori Harris here at the EBI, here’s a classic paper [1,2] on the social problems of building biomedical ontologies. This paper is worth reading (or re-reading) because it makes lots of relevant points about the use and abuse of research and how people misunderstand each other [3]. It’s funny (and available Open Access too) plus how many papers do you read with an abstract written in the style of Big Bard Bill Shakespeare?

ABSTRACT: Two households, both alike in dignity, In fair Genomics, where we lay our scene, (One, comforted by its logic’s rigour, Claims ontology for the realm of pure, The other, with blessed scientist’s vigour, Acts hastily on models that endure), From ancient grudge break to new mutiny, When ‘being’ drives a fly-man to blaspheme. From forth the fatal loins of these two foes, Researchers to unlock the book of life; Whole misadventured piteous overthrows, Can with their work bury their clans’ strife. The fruitful passage of their GO-mark’d love, And the continuance of their studies sage, Which, united, yield ontologies undreamed-of, Is now the hour’s traffic of our stage; The which if you with patient ears attend, What here shall miss, our toil shall strive to mend.

So if you read the paper, you have to ask yourself, are you a Montague or a Capulet?

References

  1. Carole Goble and Chris Wroe (2004). The Montagues and the Capulets Comparative and Functional Genomics, 5 (8), 623-632 DOI: 10.1002/cfg.442
  2. Carole Goble (2004) The Capulets and Montagues: A plague on both your houses?, SOFG: Standards and Ontologies for Functional Genomics
  3. William Shakespeare (1596) Romeo and Juliet

[Romeo and Juliet picture via Happy Hippo Snacks]

November 5, 2009

Artemether: Entity of the Month

ArtemetherNovember’s entity of the month at ChEBI is the antimalarial drug Artemether. This accompanies release 62 of ChEBI, not just yet another incremental release but an increase of more than twentyfold in the number of entities in ChEBI, thanks to merging of data between an updated ChEBI [1] and ChEMBL [2]. ChEBI now (as of release 62) has over 455,000 total entities, compared to just under 19,000 in the previous version (release 61), see ChEBI news for details. The text below on Artemether is reproduced from the ChEBI website, where content is available under a Creative Commons license:

Artemether (CHEBI:195280) is a lipid-soluble antimalarial for the treatment of multi-drug resistant strains of Plasmodium falciparum malaria. First prepared in 1979 [3], it is a methyl ether of the naturally occurring sesquiterpene lactone (+)-artemisinin, which is isolated from the leaves of Artemisia annua L. (sweet wormwood), the traditional Chinese medicinal herb known as Qinghao. However, because of artemether’s extremely rapid mode of action (it has an elimination half-life of only 2 hours, being metabolized to dihydroartemisinin which then undergoes rapid clearance), it is used in combination with other, longer-acting, drugs. One such combination, licensed in April of this year by the WHO, is Coartem in which the artemether is mixed with lumefantrine – a racemic mixture of a synthetic fluorene derivative known formerly as benflumetol – which has a much longer and pharmacologically complementary terminal half-life of 3–6 days, allowing the two drugs to act synergistically against Plasmodium.

The molecule of artemether is interesting because of its extreme rigidity, with very few rotational bonds. Unlike quinine class antimalarial drugs, it has no nitrogen atom in its skeleton. However, an important chemical feature (and unique in drugs) is the presence of an O–O endoperoxide bridge which is essential for its antimalarial activity, as it is this bridge which is split in an interaction with heme, blocking the conversion into hemozoin and thus releasing into the parasite heme and a host of free radicals which attack the cell membrane.

Artemether is fully Rule-of-Five compliant and has recently also been under investigation as a possible candidate for cancer treatment [4,5].

GO ChEBI!

References

  1. de Matos, P., Alcantara, R., Dekker, A., Ennis, M., Hastings, J., Haug, K., Spiteri, I., Turner, S., & Steinbeck, C. (2009). Chemical Entities of Biological Interest: an update Nucleic Acids Research DOI: 10.1093/nar/gkp886
  2. Warr, W. (2009). ChEMBL. An interview with John Overington, team leader, chemogenomics at the European Bioinformatics Institute Outstation of the European Molecular Biology Laboratory (EMBL-EBI) Journal of Computer-Aided Molecular Design, 23 (4), 195-198 DOI: 10.1007/s10822-009-9260-9
  3. Li, Y. et al. (1979) K’o Hsueh T’ung Pao, 24, 667 [Chem. Abstr., 91, 211376u].
  4. Singh, N., & Panwar, V. (2006). Case Report of a Pituitary Macroadenoma Treated With Artemether Integrative Cancer Therapies, 5 (4), 391-394 DOI: 10.1177/1534735406295311
  5. Wu, Z., Gao, C., Wu, Y., Zhu, Q., Yan Chen, ., Xin Liu, ., & Chuen Liu, . (2009). Inhibitive Effect of Artemether on Tumor Growth and Angiogenesis in the Rat C6 Orthotopic Brain Gliomas Model Integrative Cancer Therapies, 8 (1), 88-92 DOI: 10.1177/1534735408330714

June 4, 2009

Improving the OBO Foundry Principles

The Old Smithy Pub by loop ohThe Open Biomedical Ontologies (OBO) are a set of reference ontologies for describing all kinds of biomedical data, see [1-5] for examples. Every year, users and developers of these ontologies gather from around the globe for a workshop at the EBI near Cambridge, UK. Following on from the first workshop last year, the 2nd OBO workshop 2009 is fast approaching.

In preparation, I’ve been revisiting the OBO Foundry documentation, part of which establishes a set of principles for ontology development. I’m wondering how they could be improved because these principles are fundamental to the whole effort. We’ve been using one of the OBO ontologies (called Chemical Entities of Biological Interest (ChEBI)) in the REFINE project to mine data from the PubMed database. OBO Ontologies like ChEBI and the Gene Ontology are really crucial to making sense of the massive data which are now common in biology and medicine – so this is stuff that matters.

The OBO Foundry Principles, a sort of Ten Commandments of Ontology (or Obology if you prefer) currently look something like this (copied directly from obofoundry.org/crit.shtml):

  1. The ontology must be open and available to be used by all without any constraint other than (a) its origin must be acknowledged and (b) it is not to be altered and subsequently redistributed under the original name or with the same identifiers.The OBO ontologies are for sharing and are resources for the entire community. For this reason, they must be available to all without any constraint or license on their use or redistribution. However, it is proper that their original source is always credited and that after any external alterations, they must never be redistributed under the same name or with the same identifiers.
  2. The ontology is in, or can be expressed in, a common shared syntax. This may be either the OBO syntax, extensions of this syntax, or OWL. The reason for this is that the same tools can then be usefully applied. This facilitates shared software implementations. This criterion is not met in all of the ontologies currently listed, but we are working with the ontology developers to have them available in a common OBO syntax.
  3. The ontologies possesses a unique identifier space within the OBO Foundry. The source of a term (i.e. class) from any ontology can be immediately identified by the prefix of the identifier of each term. It is, therefore, important that this prefix be unique.
  4. The ontology provider has procedures for identifying distinct successive versions.
  5. The ontology has a clearly specified and clearly delineated content. The ontology must be orthogonal to other ontologies already lodged within OBO. The major reason for this principle is to allow two different ontologies, for example anatomy and process, to be combined through additional relationships. These relationships could then be used to constrain when terms could be jointly applied to describe complementary (but distinguishable) perspectives on the same biological or medical entity. As a corollary to this, we would strive for community acceptance of a single ontology for one domain, rather than encouraging rivalry between ontologies.
  6. The ontologies include textual definitions for all terms. Many biological and medical terms may be ambiguous, so terms should be defined so that their precise meaning within the context of a particular ontology is clear to a human reader.
  7. The ontology uses relations which are unambiguously defined following the pattern of definitions laid down in the OBO Relation Ontology.
  8. The ontology is well documented.
  9. The ontology has a plurality of independent users.
  10. The ontology will be developed collaboratively with other OBO Foundry members.

ResearchBlogging.orgI’ve been asking all my frolleagues what they think of these principles and have got some lively responses, including some here from Allyson Lister, Mélanie Courtot, Michel Dumontier and Frank Gibson. So what do you think? How could these guidelines be improved? Do you have any specific (and preferably constructive) criticisms of these ambitious (and worthy) goals? Be bold, be brave and be polite. Anything controversial or “off the record” you can email it to me… I’m all ears.

CC-licensed picture above of the Old Smithy (pub) by Loop Oh. Inspired by Michael Ashburner‘s standing OBO joke (Ontolojoke) which goes something like this: Because Barry Smith is one of the leaders of OBO, should the project be called the OBO Smithy or the OBO Foundry? 🙂

References

  1. Noy, N., Shah, N., Whetzel, P., Dai, B., Dorf, M., Griffith, N., Jonquet, C., Rubin, D., Storey, M., Chute, C., & Musen, M. (2009). BioPortal: ontologies and integrated data resources at the click of a mouse Nucleic Acids Research DOI: 10.1093/nar/gkp440
  2. Côté, R., Jones, P., Apweiler, R., & Hermjakob, H. (2006). The Ontology Lookup Service, a lightweight cross-platform tool for controlled vocabulary queries BMC Bioinformatics, 7 (1) DOI: 10.1186/1471-2105-7-97
  3. Smith, B., Ashburner, M., Rosse, C., Bard, J., Bug, W., Ceusters, W., Goldberg, L., Eilbeck, K., Ireland, A., Mungall, C., Leontis, N., Rocca-Serra, P., Ruttenberg, A., Sansone, S., Scheuermann, R., Shah, N., Whetzel, P., & Lewis, S. (2007). The OBO Foundry: coordinated evolution of ontologies to support biomedical data integration Nature Biotechnology, 25 (11), 1251-1255 DOI: 10.1038/nbt1346
  4. Smith, B., Ceusters, W., Klagges, B., Köhler, J., Kumar, A., Lomax, J., Mungall, C., Neuhaus, F., Rector, A., & Rosse, C. (2005). Relations in biomedical ontologies Genome Biology, 6 (5) DOI: 10.1186/gb-2005-6-5-r46
  5. Bada, M., & Hunter, L. (2008). Identification of OBO nonalignments and its implications for OBO enrichment Bioinformatics, 24 (12), 1448-1455 DOI: 10.1093/bioinformatics/btn194

May 6, 2009

Michel Dumontier on Representing Biochemistry

Michel Dumontier by Tom HeathMichel Dumontier is visiting Manchester this week, he will be doing a seminar on Monday 11th of May,  here are some details for anyone who is interested in attending:

Title: Increasingly Accurate Representation of Biochemistry

Speaker: Michel Dumontier, dumontierlab.com

Time: 14.00, Monday 11th May 2009
Venue: Atlas 1, Kilburn Building, University of Manchester, number 39 on the Google Campus Map

Abstract: Biochemical ontologies aim to capture and represent biochemical entities and the relations that exist between them in an accurate manner. A fundamental starting point is biochemical identity, but our current approach for generating identifiers is haphazard and consequently integrating data is error-prone. I will discuss plausible structure-based strategies for biochemical identity whether it be at molecular level or some part thereof (e.g. residues, collection of residues, atoms, collection of atoms, functional groups) such that identifiers may be generated in an automatic and curator/database independent manner. With structure-based identifiers in hand, we will be in a position to more accurately capture context-specific biochemical knowledge, such as how a set of residues in a binding site are involved in a chemical reaction including the fact that a key nitrogen atom must first be de-protonated. Thus, our current representation of biochemical knowledge may improve such that manual and automatic methods of biocuration are substantially more accurate.

Update: Slides are now available via SlideShare.

[Creative Commons licensed picture of Michel in action at ISWC 2008 from Tom Heath]

References

  1. Michel Dumontier and Natalia Villanueva-Rosales (2009) Towards pharmacogenomics knowledge discovery with the semantic web Briefings in Bioinformatics DOI:10.1093/bib/bbn056
  2. Doug Howe et al (2008) Big data: The future of biocuration Nature 455, 47-50 doi:10.1038/455047a

April 17, 2009

The Unreasonable Effectiveness of Google

GoogleVia the Official Google Research Blog at the University of Google, Alon Halevy, Peter Norvig and Fernando Pereira have published an interesting expert opinion piece in the  March/April 2009 edition of IEEE Intelligent Systems: computer.org/intelligent. The paper talks about embracing complexity and making use of the “the unreasonable effectiveness of data” [1] drawing analogies with the “unreasonable effectiveness of mathematics” [2]. There is plenty to agree and disagree with in this provocative article which makes it an entertaining read. So what can we learn from those expert Googlers in the Googleplex? (more…)

July 6, 2008

You Know OBO? Let’s GO!

Oboe mechanics by starriseAccording to their website “The Open Biomedical Ontologies (OBO) Foundry is a collaborative experiment involving developers of science-based ontologies who are establishing a set of principles for ontology development with the goal of creating a suite of orthogonal interoperable reference ontologies in the biomedical domain”. This week they are having a workshop in Cambridge, to bring myself up to speed, here is a quick name check of some of the people involved.

November 30, 2007

Burn semantic Web, Burn!

Taking down A.I. town?

Danger! Religious Wars!The Semantic Web is (quote) “a new form of Web content that is meaningful to computers”. It will “unleash a revolution of new possibilities” using a magical “new” artificially intelligent technology called ontology. So says a much-cited article in Scientific American published back in May 2001. Most people who have read this article, fall into two camps: “believers” and “non-believers”. Let me tell you a short story about a religious war between these two groups…

An Old War Story: Chapter 1

This is a work of fiction, though as they say in Hollywood it is “based on a true story”. Characters names are real.

A crusade of semantic web believers, is started by three people called Jim Hendler, Ora Lassila and Tim Berners-Lee. At the heart of their faith is a holy scripture and a suite of sacred technology called the semantic web stack. If people use this technology, the crusaders believe, the Web would be a better place. Search engines like Google, for example, would be even smarter than they already are, because they would intelligently “know what you mean“, when you type your keywords. All this new magic comes from using good old fashioned logic, metadata and reasoning. Better Search Engines is one of the mantras of the semantic web troops as they pour onto the battlefield towards the promised land. Viva la Webolution! Charge!

A counter-attack is launched by the non-believers of this vision of the future. They rally behind a man called Clay Shirky who roars “the semantic web is doomed” at the top of his voice. Many others echo Shirky’s sentiment, including Peter Norvig, Rob McCool, Cory Doctorow and Tim O’Reilly. General Shirky makes powerful allies in battle, and he has a two-pronged attack. “Ontology is over-rated” he jeers. Led by Shirky, the non-believers capture the sacred technology, add their own firewood and put the torch to it in a very public place. The flames leap into the sky, visible for miles around.

“Burn semantic web, burn!” the non-believers cry as they gleefully dance around the fire.

The battle rages, the believers will not take this heresy lying down. They regroup and surge forward again. Death to the blasphemers! With the help of some biologists, they seek revenge using the Gene Ontology as deadly ammunition. The non-believers are confused by this tactic, they don’t know what genes are and neither do the biologists. Unfortunately, the biologists unwittingly find themselves in the middle of an epic battle they didn’t start. There are ugly skirmishes involving logic and graph theory. Dormant and hideous A.I. monsters are resurrected from their caves, where they spent the A.I. winter. These gruesome monsters make the Balrog beast from Lord of the Rings look like a childrens cuddly toy.

From the relative safety of their command centres, the leaders orchestrating the war look on. Many foot soldiers and PhD students have been slayed on the field of battle, tragic young victims of the holy war. Understandably the crusaders are unhappy. Jim Hendler isn’t pleased as he surveys the carnage and devasation. Ora Lassila is also disappointed.

“We never said that, you completely minsunderstood. You are all burning the wrong thing, using fuel we never gave you. You lied, you cheated, you faked, you changed the stakes!”

There is a lull in battle. But confusion reigns, especially among the innocent civilians and bewildered biologists.

(End of chapter 1)

Epilogue

As of the winter of 2007, the semantic web fire is still burning. While I warm myself next to it, using all the juicy metadata as material for my PhD, it is still too early to predict just how useful the technology is going to be. It doesn’t really matter if you’re a “believer”, a “non-believer” or completely agnostic about the semantic web. The religious war beween the two sides tells you more about human behaviour, than it does about the utility of the technology. Optimists profit from making bold claims to get noticed on the battlefield. Critics are more cynical, furthering their own careers by countering the optimists claims. Other people interpret the interpretations of the cynics second-hand. Thanks to cumulative error, or the Chinese whispers effect, everyone gets really upset. The original optimists vision has been changed in ways they didn’t expect.

It’s a very natural and human story amidst all the “artificial” machine intelligence.

Ora, Jim and Tim have done quite well out of the fighting. Google Scholar reckons their original article has been cited nearly 5000 times. That is a lot of attention, in scientific circles, a veritable blockbuster hit. At the time of writing, not even Albert Einstein can match that, and his ideas are much more important than the semantic web probably ever will be. Many good scientists with important ideas can only dream of publishing a paper that is as heavily cited as that infamous Scientific American article. So which do you think would most scientists prefer:

  • Being internationally known and talked about, but misunderstood by large groups of people?
  • Being relatively unknown, ignored but well understood by a small and obscure group of people?

Neither is ideal but I think in most cases, there is only one thing in the world worse than being talked about, and that is not being talked about.

We have reached the end of chapter 1 of this little story. Wouldn’t it be nice if Chapter 2 was less bloody? Perhaps the two sides could focus more on facts and evidence, rather than the beliefs, opinions, marketing, hype and “visions” that have dominated the battle so far. As the winter solstice approaches and the new year beckons, can we give peace, diplomacy and above all SCIENCE a chance?

The Moral of the Story (so far)

The moral of this old war story is simple. Religions of various kinds have been known to make people commit horrendous and completely unreasonable war crimes. Nobody is innocent. So if you don’t like a fight, steer well clear of religious wars.

Acknowledgements

  1. The “burn” idea comes from Leftfield with John Lydon (1995) Open Up “Burn Hollywood, Burn! Taking down Tinseltown
  2. Thanks to Carole for the idea of using fiction to illustrate science see Carole Goble and Chris Wroe (2005) The Montagues and the Capulets: In fair Genomics, where we lay our scene… Comparative and Functional Genomics 5(8):623-632 DOI:10.1002/cfg.442 seeAlso Shakespearean Genomics: a plague on both your houses)
  3. This post, originally published on nodalpoint

October 8, 2006

Bio-Ignorance: Communicating Biology to Computer Scientists

The Human GenomeMany computer scientists and software engineers are not familiar with basic biology or bioinformatics. Many biologists and bioinformaticians are not familiar with basic computer science or software engineering. This article points to some resources that can help with the former, and asks, what can be done about the latter?

Progress in both computer science and biology is closely linked and dependent on people understanding each others strange language, cross-pollinating ideas and creating technology which hopefully has hybrid vigour. So for example, biologists and bioinformaticians have a healthy apetite for all kinds of better, cheaper, faster and sometimes novel computation. This requires they understand basic computer science and software enginnering. In the other direction, computer scientists often need realistic scenarios to motivate the invention, development and testing of genuinely novel technology. As for the software engineers, more on them later…

It sounds great, but before you can even say the words “inter-discplinary”, there are considerable barriers to communication. The various camps speak different languages, and have radically different cultures. To illustrate this communication breakdown, here is a story from the lab where I work. A while ago, I was discussing the Gene Ontology with a colleague, who shall remain anonymous. This colleague was educated, doing PhD level research and what I’d consider a fairly typical computer scientist. Soon the conversation turned to chromosomes, and they asked me:

“What is a Chromosome?”

Initially I was shocked. How could somebody not know what a chromosome was? Had they never read a newspaper? Never watched the television? Surely, most people have at least a vague idea what a chromosome is? After recovering from the shock, I told this person that according to the Gene Ontology a chromosome is “a very long molecule of DNA and associated proteins that carries hereditary information.” Perhaps this bio-ignorance is an extreme case, but unfortunately, it is all too common. Many computer scientists and software engineers I know stopped studying biology as soon as they possibly could, opting for the so-called “harder” sciences: physics, chemistry and mathematics. Consequently, many (but not all) computer scientists are bio-ignorant. What can we do about it? We really need to understand each other if we are going to make any progress. How can we improve communication between biologists and computer scientists?

Part of the solution to this problem is well-written literature that explains basic concepts quickly and clearly without getting bogged down in jargon or stuck on esoteric details, see the references below for some examples. One of my personal favourites is a little book called The Human Genome: a beginner’s guide to the chemical code of life authored by Jeremy Cherfas. This book is lavishly illustrated and beautifully written, but most importantly of all at 72 pages it is blisteringly concise, so stands a chance of being read by computer geeks and nerds. It is even funny in places, the Nobel laureate and geneticist Thomas Hunt Morgan is amusingly depicted as a red-eyed wild type, just like the fruit flies he studied. Anyway, I lent my copy of said book to my computer science buddy, and they learnt not just what chromosomes are, but also a little bit about why Biology and Genetics are such fascinating subjects.

The literature listed below can help one-way understanding of biology by outsiders, but communication is a two-way street. What about the other direction? Is there any literature that explains computer science and software engineering specifically to biologists and bioinformaticians? I don’t know of any particularly good examples, that are concise, well written and illustrated, but perhaps you do. I’ve frequently found bioinformaticians and biologists misunderstand what computer science is about, and confuse it with software engineering, but that is another story. The moral of this story is, don’t be surprised if people working in different fields to you lack a basic understanding of what you consider fundamental concepts that everybody knows. If they are bio-ignorant computer scientists, you should patiently and tirelessly explain yourself and maybe point to some of the resources below. Maybe we can understand each other just a little better.

References

  1. Anonymous GO:0005694 Chromosome: A very long molecule of DNA AmiGO! Your friend in the Gene Ontology
  2. Alvis Brazma, Helen Parkinson, Thomas Schlitt and Mohammadreza Shojatalab (2001) All you need to know about biology in twenty pages European Bioinformatics Institute (EMBL-EBI) (A technical introduction, written for EBI employees, but useful elsewhere)
  3. Jeremy Cherfas (2002) The Human Genome: a beginner’s guide to the chemical code of life (isbn:0751337161) Dorling Kindersley (A quick but informative introduction that your granny could understand)
  4. Jeremy Cherfas (2006) International Plant Genetic Resources Institute (IPGRI) public awareness blog IPGRI, Rome, Italy. (Some deserved nodalpoint Google Juice for these news and press releasess)
  5. Carole Goble and Chris Wroe (2005) The Montagues and the Capulets: In fair Genomics, where we lay our scene… Comparative and Functional Genomics 5(8):623-632 (A paper describing communication breakdown between two different research “houses”, very possibly the only paper on genomics that will make you laugh. seeAlso Shakespearean Genomics: a plague on both your houses)
  6. John Gribbin Dorling Kindersley’s Essential Science: Human Genome, Global warming, Expanding universe, Food for the future, Digital revolution and How the brain works http://www.dk.com (Some interesting books here)
  7. John W. Kimball Chromosomes Kimball’s Biology Pages (How does John Kimball manage to write so much good introductory material sabout Biology?)
  8. John Bonham, John Paul Jones and Jimmy Page (1969) Communication Breakdown Led Zeppelin (Communication breakdown, it’s always the same, I’m having a nervous breakdown, drive me insane!)
  9. This post was originally published on nodalpoint with comments.

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