Nonfiction > Harvard Classics > Charles Robert Darwin > Origin of Species
The Harvard Classics.  1909–14.
IV. Natural Selection; or the Survival of the Fittest
Natural Selection: Its Power Compared with Man’s Selection
HOW will the struggle for existence, briefly discussed in the last chapter, act in regard to variation? Can the principle of selection, which we have seen is so potent in the hands of man, apply under nature? I think we shall see that it can act most efficiently. Let the endless number of slight variations and individual differences occurring in our domestic productions, and, in a lesser degree, in those under nature, be borne in mind; as well as the strength of the hereditary tendency. Under domestication, it may be truly said that the whole organisation becomes in some degree plastic. But the variability, which we almost universally meet with in our domestic productions, is not directly produced, as Hooker and Asa Gray have well remarked, by man; he can neither originate varieties, nor prevent their occurrence; he can preserve and accumulate such as do occur. Unintentionally he exposes organic beings to new and changing conditions of life, and variability ensues; but similar changes of conditions might and do occur under nature. Let it also be borne in mind how infinitely complex and close-fitting are the mutual relations of all organic beings to each other and to their physical conditions of life; and consequently what infinitely varied diversities of structure might be of use to each being under changing conditions of life. Can it, then, be thought improbable, seeing that variations useful to man have undoubtedly occurred, that other variations useful in some way to each being in the great and complex battle of life, should occur in the course of many successive generations? If such do occur, can we doubt (remembering that many more individuals are born than can possibly survive) that individuals having any advantage, however slight, over others, would have the best chance of surviving and of procreating their kind? On the other hand, we may feel sure that any variation in the least degree injurious would be rigidly destroyed. This preservation of favourable individual differences and variations, and the destruction of those which are injurious, I have called Natural Selection, or the Survival of the Fittest. Variations neither useful nor injurious would not be affected by natural selection, and would be left either a fluctuating element, as perhaps we see in certain polymorphic species, or would ultimately become fixed, owing to the nature of the organism and the nature of the conditions.  1
  Several writers have misapprehended or objected to the term Natural Selection. Some have even imagined that natural selection induces variability, whereas it implies only the preservation of such variations as arise and are beneficial to the being under its conditions of life. No one objects to agriculturists speaking of the potent effects of man’s selection; and in this case the individual differences given by nature, which man for some object selects, must of necessity first occur. Others have objected that the term selection implies conscious choice in the animals which become modified; and it has even been urged that, as plants have no volition, natural selection is not applicable to them! In the literal sense of the word, no doubt, natural selection is a false term; but who ever objected to chemists speaking of the elective affinities of the various elements?—and yet an acid cannot strictly be said to elect the base with which it in preference combines. It has been said that I speak of natural selection as an active power or Deity; but who objects to an author speaking of the attraction of gravity as ruling the movements of the planets? Every one knows what is meant and is implied by such metaphorical expressions; and they are almost necessary for brevity. So again it is difficult to avoid personifying the word Nature; but I mean by Nature, only the aggregate action and product of many natural laws, and by laws the sequence of events as ascertained by us. With a little familiarity such superficial objections will be forgotten.  2
  We shall best understand the probable course of natural selection by taking the case of a country undergoing some slight physical change, for instance, of climate. The proportional numbers of its inhabitants will almost immediately undergo a change, and some species will probably become extinct. We may conclude, from what we have seen of the intimate and complex manner in which the inhabitants of each country are bound together, that any change in the numerical proportions of the inhabitants, independently of the change of climate itself, would seriously affect the others. If the country were open on its borders, new forms would certainly immigrate, and this would likewise seriously disturb the relations of some of the former inhabitants. let it be remembered how powerful the influence of a single introduced tree or mammal has been shown to be. But in the case of an island, or of a country partly surrounded by barriers, into which new and better adapted forms could not freely enter, we should then have places in the economy of nature which would assuredly be better filled up, if some of the original inhabitants were in some manner modified; for, had the area been open to immigration, these same places would have been seized on by intruders. In such cases, slight modifications, which in any way favoured the individuals of any species, by better adapting them to their altered conditions, would tend to be preserved; and natural selection would have free scope for the work of improvement.  3
  We have good reason to believe, as shown in the first chapter, that changes in the conditions of life give a tendency to increased variability; and in the foregoing cases the conditions have changed, and this would manifestly be favourable to natural selection, by affording a better chance of the occurrence of profitable variations. Unless such occur, natural selection can do nothing. Under the term of “variations,” it must never be forgotten that mere individual differences are included. As man can produce a great result with his domestic animals and plants by adding up in any given direction individual differences, so could natural selection, but far more easily from having incomparably longer time for action. Nor do I believe that any great physical change, as of climate, or any unusual degree of isolation to check immigration, is necessary in order that new and unoccupied places should be left, for natural selection to fill up by improving some of the varying inhabitants. For as all the inhabitants of each country are struggling together with nicely balanced forces, extremely slight modifications in the structure or habits of one species would often give it an advantage over others; and still further modifications of the same kind would often still further increase the advantage, as long as the species continued under the same conditions of life and profited by similar means of subsistence and defence. No country can be named in which all the native inhabitants are now so perfectly adapted to each other and to the physical conditions under which they live, that none of them could be still better adapted or improved; for in all countries, the natives have been so far conquered by naturalised productions, that they have allowed some foreigners to take firm possession of the land. And as foreigners have thus in every country beaten some of the natives, we may safely conclude that the natives might have been modified with advantage, so as to have better resisted the intruders.  4
  As man can produce, and certainly has produced, a great result by his methodical and unconscious means of selection, what may not natural selection effect? Man can act only on external and visible characters: Nature, if I may be allowed to personify the natural preservation or survival of the fittest, cares nothing for appearances, except in so far as they are useful to any being. She can act on every internal organ, on every shade of constitutional difference, on the whole machinery of life. Man selects only for his own good: Nature only for that of the being which she tends. Every selected character is fully exercised by her, as is implied by the fact of their selection. Man keeps the natives of many climates in the same country; he seldom exercises each selected character in some peculiar and fitting manner; he feeds a long and a short beaked pigeon on the same food; he does not exercise a long-backed or long-legged quadruped in any peculiar manner; he exposes sheep with long and short wool to the same climate. He does not allow the most vigorous males to struggle for the females. He does not rigidly destroy all inferior animals, but protects during each varying season, as far as lies in his power, all his productions. He often begins his selection by some half-monstrous form; or at least by some modification prominent enough to catch the eye or to be plainly useful to him. Under nature, the slightest differences of structure or constitution may well turn the nicely balanced scale in the struggle for life, and so be preserved. How fleeting are the wishes and efforts of man! how short his time! and consequently how poor will be his results, compared with those accumulated by Nature during whole geological periods! Can we wonder, then, that Nature’s productions should be far “truer” in character than man’s productions; that they should be infinitely better adapted to the most complex conditions of life, and should plainly bear the stamp of far higher workmanship?  5
  It may metaphorically be said that natural selection is daily and hourly scrutinising, throughout the world, the slightest variations; rejecting those that are bad, preserving and adding up all that are good; silently and insensibly working, whenever and wherever opportunity offers, at the improvement of each organic being in relation to its organic and inorganic conditions of life. We see nothing of these slow changes in progress, until the hand of time has marked the lapse of ages, and then so imperfect is our view into long-past geological ages, that we see only that the forms of life are now different from what they formerly were.  6
  In order that any great amount of modification should be effected in a species, a variety when once formed must again, perhaps after a long interval of time, vary or present individual differences of the same favourable nature as before; and these must be again preserved, and so onwards step by step. Seeing that individual differences of the same kind perpetually recur, this can hardly be considered as an unwarrantable assumption. But whether it is true, we can judge only by seeing how far the hypothesis accords with and explains the general phenomena of nature. On the other hand, the ordinary belief that the amount of possible variation is a strictly limited quantity is likewise a simple assumption.  7
  Although natural selection can act only through and for the good of each being, yet characters and structures, which we are apt to consider as of very trifling importance, may thus be acted on. When we see leaf-eating insects green, and bark-feeders mottled-grey; the alpine ptarmigan white in winter, the red grouse the colour of heather, we must believe that these tints are of service to these birds and insects in preserving them from danger. Grouse, if not destroyed at some period of their lives, would increase in countless numbers; they are known to suffer largely from birds of prey; and hawks are guided by eyesight to their prey—so much so, that on parts of the Continent persons are warned not to keep white pigeons, as being the most liable to destruction. Hence natural selection might be effective in giving the proper colour to each kind of grouse, and in keeping that colour, when once acquired, true and constant. Nor ought we to think that the occasional destruction of an animal of any particular colour would produce little effect: we should remember how essential it is in a flock of white sheep to destroy a lamb with the faintest trace of black. We have seen how the colour of the hogs, which feed on the “paint-root” in Virginia, determines whether they shall live or die. In plants, the down on the fruit and the colour of the flesh are considered by botanists as characters of the most trifling importance: yet we hear from an excellent horticulturist, Downing, that in the United States, smooth-skinned fruits suffer far more from a beetle, a Curculio, than those with down; that purple plums suffer far more from a certain disease than yellow plums; whereas another disease attacks yellow-fleshed peaches far more than those with other coloured flesh. If, with all the aids of art, these slight differences make a great difference in cultivating the several varieties, assuredly, in a state of nature, where the trees would have to struggle with other trees, and with a host of enemies, such differences would effectually settle which variety, whether a smooth or downy, a yellow or purple fleshed fruit, should succeed.  8
  In looking at many small points of difference between species, which, as far as our ignorance permits us to judge, seem quite unimportant, we must not forget that climate, food, &c., have no doubt produced some direct effect. It is also necessary to bear in mind that, owing to the law of correlation, when one part varies, and the variations are accumulated through natural selection, other modifications, often of the most unexpected nature, will ensue.  9
  As we see that those variations which, under domestication, appear at any particular period of life, tend to reappear in the offspring at the same period; for instance, in the shape, size, and flavour of the seeds of the many varieties of our culinary and agricultural plants; in the caterpillar and cocoon stages of the varieties of the silk-worm; in the eggs of poultry, and in the colour of the down of their chickens; in the horns of our sheep and cattle when nearly adult; so in a state of nature natural selection will be enabled to act on and modify organic beings at any age, by the accumulation of variations profitable at that age, and by their inheritance at a corresponding age. If it profit a plant to have its seeds more and more widely disseminated by the wind, I can see no greater difficulty in this being effected through natural selection, than in the cotton planter increasing and improving by selection the down in the pods on his cotton trees. Natural selection may modify and adapt the larva of an insect to a score of contingencies, wholly different from those which concern the mature insect; and these modifications may affect, through correlation, the structure of the adult. So, conversely, modifications in the adult may affect the structure of the larva; but in all cases natural selection will ensure that they shall not be injurious: for if they were so, the species would become extinct.  10
  Natural selection will modify the structure of the young in relation to the parent, and of the parent in relation to the young. In social animals it will adapt the structure of each individual for the benefit of the whole community, if the community profits by the selected change. What natural selection cannot do, is to modify the structure of one species, without giving it any advantage, for the good Of another species; and though statements to this effect may be found in works of natural history, I cannot find one case which will bear investigation. A structure used only once in an animal’s life, if of high importance to it, might be modified to any extent by natural selection; for instance, the great jaws possessed by certain insects, used exclusively for opening the cocoon—or the hard tip to the beak of unhatched birds, used for breaking the egg. It has been asserted, that of the best short-beaked tumbler pigeons a greater number perish in the egg than are able to get out of it; so that fanciers assist in the act of hatching. Now if nature had to make the beak of a full-grown pigeon very short for the bird’s own advantage, the process of modification would be very slow, and there would be simultaneously the most rigorous selection of all the young birds within the egg, which had the most powerful and hardest beaks, for all with weak beaks would inevitably perish; or, more delicate and more easily broken shells might be selected, the thickness of the shell being known to vary like every other structure.  11
  It may be well here to remark that with all beings there must be much fortuitous destruction, which can have little or no influence on the course of natural selection. For instance a vast number of eggs or seeds are annually devoured, and these could be modified through natural selection only if they varied in some manner which protected them from their enemies. Yet many of these eggs or seeds would perhaps, if not destroyed, have yielded individuals better adapted to their conditions of life than any of these which happened to survive. So again a vast number of mature animals and plants, whether or not they be the best adapted to their conditions, must be annually destroyed by accidental causes, which would not be in the least degree mitigated by certain changes of structure or constitution which would in other ways be beneficial to the species. But let the destruction of the adults be ever so heavy, if the number which can exist in any district be not wholly kept down by such causes,—or again let the destruction of eggs or seeds be so great that only a hundredth or a thousandth part are developed,—yet of those which do survive, the best adapted individuals, supposing that there is any variability in favourable direction, will tend to propagate their kind in larger numbers than the less well adapted. If the numbers be wholly kept down by the causes just indicated, as will often have been the case, natural selection will be powerless in certain beneficial directions; but this is no valid objection to its efficiency at other times and in other ways; for we are far from having any reason to suppose that many species ever undergo modification and improvement at the same time in the same area.  12


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Thursday, 17 October 2002, 12:34 PM EST

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Researchers from Lucent Technologies' Bell Labs are tapping the individuality of the human voice to generate unique cryptographic keys for computer users. Under the researchers' scheme, a user speaks a password, and the system listens for both the correct word and the correct voice.

The method uses the random variability of people's voices to add a layer of security to even a simple password, said Fabian Monrose, a member of technical staff at Bell Labs. "The randomness of [a] key is drawn from both the pass-phrase that is spoken and the speech patterns of the user... speaking it," he said. The more randomness contained in the information the key is constructed from, the harder the key is to figure out.

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1.  Optimus Primer: A PCR enrichment primer design program for next-generation sequencing of human exonic regions
BMC Research Notes  2010;3:185.
Polymerase chain reaction (PCR) remains a simple, flexible, and inexpensive method for enriching genomic regions of interest for next-generation sequencing. In order to utilize PCR in this context, a major challenge facing researchers is how to generate a very large number of functional PCR primers that will successfully generate useable amplicons. For instance, in an exon-only re-sequencing project targeting 100 genes, each with 10 exons, 1,000 pairs of primers are required. In fact, the reality is often more complex as each gene might have several isoforms and large exons need to be divided to maintain the desired amplicon size. With only a list of gene names, our program Optimus Primer (OP) automatically takes into account all these variables, and can generate primers with no need to provide genome coordinates. More importantly however, OP, unlike other primer design programs, uniquely utilizes Primer3 in an iterative manner that allows the user to progressively design up to four iterations of primer designs. Through a single interface, the user can specify up to four different design parameters with different stringencies, thus increasing the probability that a functional PCR primer pair will be designed for all regions of interest in a single pass of the pipeline.
To demonstrate the effectiveness of the program, we designed PCR primers against 77 genes located in loci associated with ulcerative colitis as part of a candidate gene re-sequencing experiment. We achieved an experimental success rate of 93% or 472 out of 508 amplicons spanning the exonic regions of the 77 genes. Moreover, by automatically passing amplicons that failed primer design through three additional iterations of design parameters, we achieved an additional 170 successful primer pairs or 34% more in a single pass of OP than by conventional methods.
With only a gene list and PCR parameters, a user can produce hundreds of PCR primer designs for regions of interest with a high probability of success in a very short amount of time. Optimus Primer is an essential tool for researchers who want to pursue PCR-based enrichment strategies for next-generation re-sequencing applications. The program can be accessed via website at
PMCID: PMC2916007  PMID: 20609249
Nature genetics  2014;46(6):629-634.
Hematological traits are important clinical parameters. To test the role of rare and low-frequency coding variants on hematological traits, we analyzed hemoglobin, hematocrit, white blood cell (WBC) and platelet count in 31,340 individuals genotyped on an exome array. We identified several missense variants of CXCR2 associated with reduced WBC count (gene-based P=2.6×10−13). In a separate family-based re-sequencing study, we identified a novel loss-of-function CXCR2 frameshift mutation in a pedigree with congenital neutropenia that abolished ligand-induced CXCR2 signal transduction and chemotaxis. We also identified novel missense or splice site variants in key hematopoiesis regulators (EPO, TRF2, HBB, TUBB1, SH2B3) associated with blood cell traits. Finally, we were able to detect associations between the rare somatic JAK2 p.Val617Phe mutation and platelet count (P=3.9×10−22) as well as hemoglobin (P=0.002), hematocrit (P=9.5×10−7) and WBC (P=3.1×10−5). In conclusion, exome arrays complement GWAS in identifying new variants that contribute to complex human traits.
PMCID: PMC4050975  PMID: 24777453
PLoS Genetics  2013;9(9):e1003723.
Author Summary
PMCID: PMC3772057  PMID: 24068945
4.  Genetic association analysis highlights new loci that modulate hematological trait variation in Caucasians and African Americans
Human genetics  2010;129(3):307-317.
Red blood cell, white blood cell, and platelet measures, including their count, sub-type and volume, are important diagnostic and prognostic clinical parameters for several human diseases. To identify novel loci associated with hematological traits, and compare the architecture of these phenotypes between ethnic groups, the CARe Project genotyped 49,094 single nucleotide polymorphisms (SNPs) that capture variation in ~2,100 candidate genes in DNA of 23,439 Caucasians and 7,112 African Americans from five population-based cohorts. We found strong novel associations between erythrocyte phenotypes and the glucose-6 phosphate dehydrogenase (G6PD) A-allele in African Americans (rs1050828, P < 2.0 × 10−13, T-allele associated with lower red blood cell count, hemoglobin, and hematocrit, and higher mean corpuscular volume), and between platelet count and a SNP at the tropomyosin-4 (TPM4) locus (rs8109288, P = 3.0 × 10−7 in Caucasians; P = 3.0 × 10−7 in African Americans, T-allele associated with lower platelet count). We strongly replicated many genetic associations to blood cell phenotypes previously established in Caucasians. A common variant of the α-globin (HBA2-HBA1) locus was associated with red blood cell traits in African Americans, but not in Caucasians (rs1211375, P < 7 × 10−8, A-allele associated with lower hemoglobin, mean corpuscular hemoglobin, and mean corpuscular volume). Our results show similarities but also differences in the genetic regulation of hematological traits in European- and African-derived populations, and highlight the role of natural selection in shaping these differences.
PMCID: PMC3442357  PMID: 21153663
5.  Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease
Nature Genetics  2011;43(11):1066-1073.
PMCID: PMC3378381  PMID: 21983784
6.  Hundreds of variants clustered in genomic loci and biological pathways affect human height
Lango Allen, Hana | Estrada, Karol | Lettre, Guillaume | Berndt, Sonja I. | Weedon, Michael N. | Rivadeneira, Fernando | Willer, Cristen J. | Jackson, Anne U. | Vedantam, Sailaja | Raychaudhuri, Soumya | Ferreira, Teresa | Wood, Andrew R. | Weyant, Robert J. | Segrè, Ayellet V. | Speliotes, Elizabeth K. | Wheeler, Eleanor | Soranzo, Nicole | Park, Ju-Hyun | Yang, Jian | Gudbjartsson, Daniel | Heard-Costa, Nancy L. | Randall, Joshua C. | Qi, Lu | Smith, Albert Vernon | Mägi, Reedik | Pastinen, Tomi | Liang, Liming | Heid, Iris M. | Luan, Jian'an | Thorleifsson, Gudmar | Winkler, Thomas W. | Goddard, Michael E. | Lo, Ken Sin | Palmer, Cameron | Workalemahu, Tsegaselassie | Aulchenko, Yurii S. | Johansson, Åsa | Zillikens, M.Carola | Feitosa, Mary F. | Esko, Tõnu | Johnson, Toby | Ketkar, Shamika | Kraft, Peter | Mangino, Massimo | Prokopenko, Inga | Absher, Devin | Albrecht, Eva | Ernst, Florian | Glazer, Nicole L. | Hayward, Caroline | Hottenga, Jouke-Jan | Jacobs, Kevin B. | Knowles, Joshua W. | Kutalik, Zoltán | Monda, Keri L. | Polasek, Ozren | Preuss, Michael | Rayner, Nigel W. | Robertson, Neil R. | Steinthorsdottir, Valgerdur | Tyrer, Jonathan P. | Voight, Benjamin F. | Wiklund, Fredrik | Xu, Jianfeng | Zhao, Jing Hua | Nyholt, Dale R. | Pellikka, Niina | Perola, Markus | Perry, John R.B. | Surakka, Ida | Tammesoo, Mari-Liis | Altmaier, Elizabeth L. | Amin, Najaf | Aspelund, Thor | Bhangale, Tushar | Boucher, Gabrielle | Chasman, Daniel I. | Chen, Constance | Coin, Lachlan | Cooper, Matthew N. | Dixon, Anna L. | Gibson, Quince | Grundberg, Elin | Hao, Ke | Junttila, M. Juhani | Kaplan, Lee M. | Kettunen, Johannes | König, Inke R. | Kwan, Tony | Lawrence, Robert W. | Levinson, Douglas F. | Lorentzon, Mattias | McKnight, Barbara | Morris, Andrew P. | Müller, Martina | Ngwa, Julius Suh | Purcell, Shaun | Rafelt, Suzanne | Salem, Rany M. | Salvi, Erika | Sanna, Serena | Shi, Jianxin | Sovio, Ulla | Thompson, John R. | Turchin, Michael C. | Vandenput, Liesbeth | Verlaan, Dominique J. | Vitart, Veronique | White, Charles C. | Ziegler, Andreas | Almgren, Peter | Balmforth, Anthony J. | Campbell, Harry | Citterio, Lorena | De Grandi, Alessandro | Dominiczak, Anna | Duan, Jubao | Elliott, Paul | Elosua, Roberto | Eriksson, Johan G. | Freimer, Nelson B. | Geus, Eco J.C. | Glorioso, Nicola | Haiqing, Shen | Hartikainen, Anna-Liisa | Havulinna, Aki S. | Hicks, Andrew A. | Hui, Jennie | Igl, Wilmar | Illig, Thomas | Jula, Antti | Kajantie, Eero | Kilpeläinen, Tuomas O. | Koiranen, Markku | Kolcic, Ivana | Koskinen, Seppo | Kovacs, Peter | Laitinen, Jaana | Liu, Jianjun | Lokki, Marja-Liisa | Marusic, Ana | Maschio, Andrea | Meitinger, Thomas | Mulas, Antonella | Paré, Guillaume | Parker, Alex N. | Peden, John F. | Petersmann, Astrid | Pichler, Irene | Pietiläinen, Kirsi H. | Pouta, Anneli | Ridderstråle, Martin | Rotter, Jerome I. | Sambrook, Jennifer G. | Sanders, Alan R. | Schmidt, Carsten Oliver | Sinisalo, Juha | Smit, Jan H. | Stringham, Heather M. | Walters, G.Bragi | Widen, Elisabeth | Wild, Sarah H. | Willemsen, Gonneke | Zagato, Laura | Zgaga, Lina | Zitting, Paavo | Alavere, Helene | Farrall, Martin | McArdle, Wendy L. | Nelis, Mari | Peters, Marjolein J. | Ripatti, Samuli | van Meurs, Joyce B.J. | Aben, Katja K. | Ardlie, Kristin G | Beckmann, Jacques S. | Beilby, John P. | Bergman, Richard N. | Bergmann, Sven | Collins, Francis S. | Cusi, Daniele | den Heijer, Martin | Eiriksdottir, Gudny | Gejman, Pablo V. | Hall, Alistair S. | Hamsten, Anders | Huikuri, Heikki V. | Iribarren, Carlos | Kähönen, Mika | Kaprio, Jaakko | Kathiresan, Sekar | Kiemeney, Lambertus | Kocher, Thomas | Launer, Lenore J. | Lehtimäki, Terho | Melander, Olle | Mosley, Tom H. | Musk, Arthur W. | Nieminen, Markku S. | O'Donnell, Christopher J. | Ohlsson, Claes | Oostra, Ben | Palmer, Lyle J. | Raitakari, Olli | Ridker, Paul M. | Rioux, John D. | Rissanen, Aila | Rivolta, Carlo | Schunkert, Heribert | Shuldiner, Alan R. | Siscovick, David S. | Stumvoll, Michael | Tönjes, Anke | Tuomilehto, Jaakko | van Ommen, Gert-Jan | Viikari, Jorma | Heath, Andrew C. | Martin, Nicholas G. | Montgomery, Grant W. | Province, Michael A. | Kayser, Manfred | Arnold, Alice M. | Atwood, Larry D. | Boerwinkle, Eric | Chanock, Stephen J. | Deloukas, Panos | Gieger, Christian | Grönberg, Henrik | Hall, Per | Hattersley, Andrew T. | Hengstenberg, Christian | Hoffman, Wolfgang | Lathrop, G.Mark | Salomaa, Veikko | Schreiber, Stefan | Uda, Manuela | Waterworth, Dawn | Wright, Alan F. | Assimes, Themistocles L. | Barroso, Inês | Hofman, Albert | Mohlke, Karen L. | Boomsma, Dorret I. | Caulfield, Mark J. | Cupples, L.Adrienne | Erdmann, Jeanette | Fox, Caroline S. | Gudnason, Vilmundur | Gyllensten, Ulf | Harris, Tamara B. | Hayes, Richard B. | Jarvelin, Marjo-Riitta | Mooser, Vincent | Munroe, Patricia B. | Ouwehand, Willem H. | Penninx, Brenda W. | Pramstaller, Peter P. | Quertermous, Thomas | Rudan, Igor | Samani, Nilesh J. | Spector, Timothy D. | Völzke, Henry | Watkins, Hugh | Wilson, James F. | Groop, Leif C. | Haritunians, Talin | Hu, Frank B. | Kaplan, Robert C. | Metspalu, Andres | North, Kari E. | Schlessinger, David | Wareham, Nicholas J. | Hunter, David J. | O'Connell, Jeffrey R. | Strachan, David P. | Wichmann, H.-Erich | Borecki, Ingrid B. | van Duijn, Cornelia M. | Schadt, Eric E. | Thorsteinsdottir, Unnur | Peltonen, Leena | Uitterlinden, André | Visscher, Peter M. | Chatterjee, Nilanjan | Loos, Ruth J.F. | Boehnke, Michael | McCarthy, Mark I. | Ingelsson, Erik | Lindgren, Cecilia M. | Abecasis, Gonçalo R. | Stefansson, Kari | Frayling, Timothy M. | Hirschhorn, Joel N
Nature  2010;467(7317):832-838.
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence phenotype. Genome-wide association (GWA) studies have identified >600 variants associated with human traits1, but these typically explain small fractions of phenotypic variation, raising questions about the utility of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait2,3. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P=0.016), and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants, and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented amongst variants that alter amino acid structure of proteins and expression levels of nearby genes. Our data explain ∼10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to ∼16% of phenotypic variation (∼20% of heritable variation). Although additional approaches are needed to fully dissect the genetic architecture of polygenic human traits, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
PMCID: PMC2955183  PMID: 20881960
Nucleic Acids Research  2008;36(22):6959-6976.
Poly(ADP-ribose) (pADPr) is a polymer assembled from the enzymatic polymerization of the ADP-ribosyl moiety of NAD by poly(ADP-ribose) polymerases (PARPs). The dynamic turnover of pADPr within the cell is essential for a number of cellular processes including progression through the cell cycle, DNA repair and the maintenance of genomic integrity, and apoptosis. In spite of the considerable advances in the knowledge of the physiological conditions modulated by poly(ADP-ribosyl)ation reactions, and notwithstanding the fact that pADPr can play a role of mediator in a wide spectrum of biological processes, few pADPr binding proteins have been identified so far. In this study, refined in silico prediction of pADPr binding proteins and large-scale mass spectrometry-based proteome analysis of pADPr binding proteins were used to establish a comprehensive repertoire of pADPr-associated proteins. Visualization and modeling of these pADPr-associated proteins in networks not only reflect the widespread involvement of poly(ADP-ribosyl)ation in several pathways but also identify protein targets that could shed new light on the regulatory functions of pADPr in normal physiological conditions as well as after exposure to genotoxic stimuli.
PMCID: PMC2602769  PMID: 18981049

Results 1-7 (7)


SOT (Semi-Off-Topic) In Cocoon 2's TODO list under "medium" prioriy, it meantions that we should have this great and mighty profiler. In the past I have given it allot of thought, because I wanted to implement it. Unfortunately, due to the SAX model, this feature will add more complexity than is really worth. The reason is that every stage is executed simultaneously. A Generator's startElement() will propogate through the different stages and cause the Transformers and Serializers to act on it before the next SAX event is called. We can easily approach a rough view of the performance at setup and page generation levels, but there is nothing that will let us easily split generation from transformation and serialization. Consider the following simple sequence diagram: Generator Transformer Transformer Serializer | | | | | start "foo" | | | +--------------->| start "foo" | | | +---------------->| start "bar" | | end "foo" | +--------------->| +--------------->| end "foo" | | | +---------------->| end "bar" | | | +--------------->| | | | | At this approach, you would have to find the difference in timings. You find the timing it takes for the "start:foo" event from the Generator to execute from beginning to end, and repeat the results for each stage. The timing for the second transformer to call and return the "start:foo" event is the time it takes for the serializer to process. You subtract that time from the time for the first transformer to call and return the "start:foo" event and you have how long the second transformer took. You repeat the algorithm by subtracting the cumulative time for the first transformer to call and return the "start:foo" event from the total time for the Generators call. You have to repeat that algorithm for EACH SAX EVENT, and add the cumulative results for each stage to find out how long the relative times are. This will degrade performance so bad, Cocoon 2 will seem like it is crawling. The biggest problem with that is what if one of the transformation stages removes the SAX event from the pipeline? You would find out how long the processing spent with each step, and with each SAX event. This will help you determine EXACTLY where in the page the slowdown occurs. The other issue is how do we measure general delays between SAX events for the Generator? My assumption is that the clock would have to be continually ticking for the generator and only subtract out the results for each stage. The good news is that with the skeleton for the new pipeline that we now have in CVS, we can implement the algorithm in a ProfilingEventPipeline object and possibly a CacheProfilingEventPipeline. Stream profiling is very easy, so it is not as major a concern. --------------------------------------------------------------------- To unsubscribe, e-mail: For additional commands, email:


You can read abstracts of papers we accepted below, or download all the abstracts in one PDF file.

Keynote Speakers

We are excited to announce the following two keynote speakers:

Emma Borg (Reading)
Monkey See, Monkey Know? Povinelli’s Problem and the need to mindread

Daniel Povinelli (2001 and elsewhere) has raised a serious and now well-known difficulty for those who wish to investigate the existence of mental state attribution (mindreading) in primates. Povinelli’s Problem holds that any non-verbal test for theory of mind will fail to provide conclusive evidence of reasoning about mental states, since a complementary behaviour-based explanation is always available which would yield the same results. This paper explores Povinelli’s Problem, asking whether it applies not only in the primate but also in the human arena, and whether we should adopt a deflationary model of social interaction in response. My conclusion, however, is that whilst Povinelli has raised a serious challenge for claims of mindreading in non-human animals, we nevertheless have good reason to resist extending the sceptical challenge to our own case.

Richard Sorabji (Oxford)
Necessity, freedom and responsibility in Aristotle's school

Aristotle was opposed to the idea that our actions had been necessary indefinitely far back. His greatest defender, Alexander, thought it would be especially damaging to moral responsibility (liability to justified praise and blame), if they had been necessary since before we were born. But he went further and claimed: our actions are not necessary even at the last moment. Although I do not agree with his view that that is required for moral responsibility, I want to assess his opponents' reply. They said the absence of last-moment necessity would make our actions inexplicable. Alexander took two steps towards a reply. (a) Motives can cause action and (b) we have more than one standing motive. Nothing need necessitate which of our standing motives would be acted on if the same causes and circumstances recurred. Whichever motive was acted on would provide explanation and cause of our different action. He implies that what is caused (that is, for Aristotle, has the appropriate type of explanation) need not be necessitated. I shall ask if his view can be defended that action unnecessitated in this way at the last moment could still be explicable.

Graduate Speakers

We are also happy to announce the following twelve graduate speakers:

Gregory Antill (UCLA)
The Ethics of Self-Fulfilling Belief

The Ethics of Belief concerns itself with the question of what we should believe. In this paper, I will concern myself with the ethics of self-fulfilling belief – the question of what we should believe about the class of propositions such that belief in the proposition makes that proposition true. Traditionally, answers diverge: evidentialists think one ought to suspend belief, while pragmatists think that one may believe whatever is best in line with ones needs.

In this paper, I will explore in more detail the reasoning involved in deliberating over self-fulfilling beliefs. I will argue that such exploration shows that the traditional account of the disagreement between pragmatists and evidentialists cannot be correct. By attending closely to self-fulfilling beliefs, we can better understand the way pragmatist and evidentialist norms actually diverge, and also learn important lessons about how to think of the norms and aims that govern theoretical deliberation more generally.

Bob Beddor (Rutgers)
Noncognitivism and Epistemic Evaluations

According to noncognitivists, moral beliefs are closely akin to desires. Moral beliefs, like desires, have a world-to-mind direction of fit, whereas non-moral beliefs have a mind-to- world direction of fit. In this paper, I offer a novel challenge for noncognitivism, thus construed. The challenge starts from the observation that both moral and non-moral beliefs are epistemically evaluable: we evaluate them based on whether they are epistemically rational and whether they constitute knowledge. Desires are not epistemically evaluable: my desire for a drink cannot be epistemically rational or irrational; similarly, it cannot constitute knowledge. A natural explanation for this difference is that only psychological states with a mind-to-world direction of fit are epistemically evaluable. But noncognitivists cannot accept this explanation, since they hold that moral beliefs have a world-to-mind direction of fit. Noncognitivists thus need to give some other explanation of why beliefs are epistemically evaluable, whereas desires are not.

Malte Bischof (St. Andrews)
Kant’s Objection to the PII in the Nova Dilucidatio

In this essay, I examine Kant's objection in the Principiorum Primorum Cognitionis Metaphysicae Nova Dilucidatio to Leibniz’s argument for the Principle of the Identity of Indiscernibles (PII) as articulated in The Leibniz-Clarke Correspondence and demonstrate its value for the contemporary debate about the PII. My examination of Kant's objection accomplishes three things. First, it fills a gap in the secondary literature since Kant's objection has not yet been examined. Second, it shows that Leibniz’s theological argument for the PII is unsuccessful even if the Principle of Sufficient Reason and the Principle of the Best are granted. Third, it rejects an argument in favor of the PII recently advanced by Michael Della Rocca’s argument for the PII.

Matthias Brinkmann (Oxford)
Governmental Intentions Don’t Matter for Legitimacy

I start with a claim about individual morality: whether your actions are permissible is largely independent from the motives and intentions from which you act. It matters what you do, not why you do it. This suggests an analogous claim for political morality: whether the decisions of a government are legitimate is largely independent from the intentions and reasons for which government acts. If this is true, the presence or absence of public reason in arguing for a policy is irrelevant to its legitimacy, even if public reason is otherwise desirable. I explore some ways to escape the analogy, but find them unconvincing.

Elena Cagnoli Fiecconi (Oxford)
Aristotle on Why Only Humans Can Think

In this paper, I argue that Aristotle, when he suggests that humans are the only animals who can think, does manage to identify some cognitive abilities that belong to humans only. These are the capacity to grasp causal relationships and the capacity to grasp generalizations. I suggest, furthermore, that thinking emerges from Aristotle’s analysis as a rather unified activity, which can be employed in high-level tasks such as thinking about the first principles of science, as well as low-level tasks such as arguing and persuading an interlocutor.

Will Fleisher (Rutgers)
Virtuous Distinctions

Virtue epistemology is a family of epistemological theories which take some notion of virtue or competence as their central explanatory concept. This family has been divided into two camps: reliabilists and responsibilists. This division has been attributed in part to a focus on different types of virtues, viz., faculty virtues and character virtues. I will argue that this distinction is unhelpful in this debate, and that we should carve up the theoretical terrain differently. I will present and defend three new distinctions. These distinctions will show us two important things: first, that responsibilists and reliabilists are actually engaged in different, complementary projects; and second, that the responsibilist critique of reliabilism misses the mark. Using these distinctions, I will present a proposed way of reducing the character virtues the responsibilists are concerned with into terms of competences. While this will give us a unified account of epistemic virtues, it is not a reduction of the responsibilist project to the reliabilist one; rather, it as a way of securing the separate importance of each project by clarifying how they relate to one another.

Jeremy Goodman (NYU)
Williamson’s earrings

I show that an old puzzle of Timothy Williamson’s supports a novel argument against physicalism.

Patrick Manzanares (Western Michigan)
The Problem of Nomological Impossibilty for Epistemic Structural Realism

The philosophical view known as Epistemic Structural Realism appeals to the concept of ‘structure’ in order to defend a version of Scientific Realism that nevertheless respects historical considerations of ontological discontinuity between successive scientific theories. It seems that the structures of some scientific theories are only continuous with the structures of successor theories when the former are characterized as nomologically impossible idealizations of the latter, since this continuity involves allowing some quantity in the formal structure of the successor theory to tend towards some physically unrealizable limit. But if this is the case, then the earlier theory cannot be physically realized. It is thus unclear in what sense the structure of the earlier theory can be said to accurately represent the physical structure of the world, since the former structure is nomologically impossible. If the nomological impossibility of the earlier theory’s structure undermines the Scientific Realist’s justification for believing in it, moreover, then the preservation of structure through theory change will fail to secure justification for the belief in the accuracy of the successor theory’s formal structure. The Scientific Realist will thus be left with no reason to believe in the structural accuracy of current scientific theories.

Michaela M. McSweeney (Princeton)
Logic, Mass, and Surrogative Representation

I argue for an analogy between mass predicates and logical constants, and develop an account of surrogative representation that accounts for the similarities between the two. One theory surrogatively represents another (its “target” theory) when it captures a certain amount of important structure in the target, but fails to exactly match the structure of the bit of reality it is trying to capture. I argue that any theory involving either numerical mass predicates or logical constants must be a surrogate theory. It follows that no theory involving logical constants can be “joint-carving”, and hence that, if we need logical constants to state our theories, it is impossible to state a joint-carving theory. I briefly discuss representation and uniqueness theorems for mass as what justifies our use of surrogate theories. In the final section of the paper, I explore some ways we might establish that a given theory stated in a language that uses logical constants is a good surrogate for our target theory. While we won't be able to prove representation and uniqueness theorems in the logic case, there are other interesting routes we might go down.

James R. Otis (Rochester)
Exclusion Arguments: A Dilemma for Interventionism

In this essay I present Kim’s (1998) exclusion argument against nonreductive physicalism. I show how List & Menzies (2009, 2010) escape the argument by revising the ex- clusion principle, denying its status as an analytic truth, and defending an interventionist theory of causation. This account of causation and the revised exclusion principle give the exact parameters by which mental causation might take place without requiring the rejection of nonreductive physicalism. I propose a dilemma for List & Menzies wherein interventionists are forced to choose between accepting disjunctive properties as difference-making causes or accepting that not all instances of causation have difference-making causes. I argue that both of these options are unsatisfying for an interventionist. The former is counterintuitive while the latter undermines the interventionist project. I conclude by reviewing potential replies to the dilemma and suggesting that they are unconvincing.

Thomas Quinn (Birkbeck)
Reduction, Representation and ‘Raising My Arm’:
A New Approach to Reduction in the Philosophy of Action

The standard account of the nature of action reduces actions to purely physical bodily events. However, some antireductionists deny that actions can be reduced, based on the fact that our concept of action cannot be analysed in purely physical terms. The antireductionist’s arguments are often dismissed based on a principle widely accepted in recent metaphysics: conceptual analysis has no bearing on metaphysical reduction. In this paper I examine the validity of this principle in a wider context, and show how this can lead to progress in the debate about action. Drawing on John Heil’s view of the relation between our thought and reality, I argue that both sides in the debate are partly right – and that we can find a middle way between reductionism and antireductionism that should be acceptable to both parties. The basis for this new approach is the recognition that whilst conceptual analysis cannot reveal the ‘deep story’ about the nature of phenomena, it does show us the limits of our ability to answer questions about these phenomena. So, whilst the existence of actions requires nothing more than physical stuff, all of the questions we can hope to answer about action will be in agential terms.

Ian Wells (MIT)
Conditionals, Conditional Probability and Simpson’s Paradox

Stalnaker’s Thesis equates the probability of an indicative conditional with the conditional probability of its consequent, conditional on its antecedent. This paper uses Simpson’s paradox to motivate a new counterexample to that equation. The counterexample draws support from a principle linking probabilities of conditionals to rational preferences.


II. Of the Nature and Properties of the Sonnet, particularly the Sonnet called Legitimate
THE LITTLE species of poem called a sonnet, which is limited in general to fourteen lines, and is rhymed and arranged according to particular laws, made its first known appearance at the beginning of the twelfth century, and in Italy. Like almost all the forms of Italian poetry, it is supposed to have originated in Provence; and it derived its name, like the composition called a Sonata, from being sounded or played; that is to say, accompanied by a musical instrument. To sound, in Italian, still means to play music; and the sonnet, of old, was never without such accompaniment. The Canzone, or Ode, like the Canzonetta, or Song,—the Chanson and Chansonette of the French,—might be chanted, or sung, with the voice only; and so might the Canto, or division, of the narrative poem; as was the case with the stanzas of Tasso, that were sung up to a late period by the Venetian gondolier. The Ballata, or ballad,—from ballare, to dance, whence our word Ball,—a species of song, the name of which has strangely wandered from its first meaning, might be danced to, also with the voice only. The Madrigal, sometimes called Madriale, or Mandriale, a small, irregular set of verses, often of the briefest and humblest description, and so named, according to the received opinion, from Mandra, or Mandria, a sheepfold, but more probably, I conceive, from the song of the mother (madre), or nursery song, implied nothing directly musical either way; though it subsequently came to mean a particular species of vocal composition in parts. But the sonnet, agreeably to its appellation, was never heard without the sounding of the lute or the guitar. This connection, as we shall see, lasted a long time; and when it ceased, it left upon the little poem a demand for treatment more than commonly musical, and implying, so to speak, the companion which it had lost.  1
  When I first began this Essay, I had entered more at large into these and other matters relative to the name and rise of the sonnet; such as a late etymology from the French word Sonnette, a sheep-bell; the strange, pedantic question, whether the species of poem originated in the Pindaric Ode, or in the Greek or Latin Epigram, things either too long or too short, and quite out of the beat of its early writers; the demand of a certain logical mode of treatment, which it was long the fashion to consider indispensably necessary; and, lastly, certain recondite musical analogies, which a late enthusiast on the subject, Mr. Capel Lofft, found between its fourteen lines and the gamut.  2
  Two of these points, however, are scarcely worth the mention here given them; and the other two, which contain germs of truth, may be briefly despatched.  3
  The fourteen lines of the Sonnet Proper, or what is called the Legitimate Sonnet, that is to say, the one written according to the laws which have prevailed in Italy ever since the time of Petrarca, are divided into two distinct portions, Major and Minor, each of which is subdivided into two also. The Major division consists of eight lines, called the Octave, which possesses but two rhymes; the Minor, of six lines, called the Sestette, which possesses never more than three; and the subdivisions or halves of these eight lines are called Quatrains, and those of the six lines Terzettes. The two rhymes of the Major division almost invariably occupy the same places; the two or three rhymes of the Minor may be varied at pleasure, but seldom close with a couplet.  4
  A few glances, however, at the sonnets themselves will be worth a hundred directions of this kind; only the student is to bear in mind, that the music of the lines is to be at once as sweet and as strong and as varied as possible, and that there should be something of a difference of tone discernible in the Major and Minor portions, as there is in the divisions of music so called, or in the two strains of an air or melody.  5
  The logical notion of the treatment of this construction of verse arose in the times when Aristotle and the schoolmen were all in all with men of letters; and it was probably not unassisted by the musical instinct which perceives questions, and replies, and solutions, in tones and cadences. The musical notion, as pushed to its excess by Mr. Lofft, 1 would appear to have been suggested to him by his confusion of Friar Guittone of Arezzo, who is understood to have first given the sonnet its right modulation, with another Friar of the same name and place, who flourished a long time before him, and who was supposed to be the inventor of counterpoint.  6
  The logical notion prevailed so long with critics of a certain scholarly and conventional turn of mind, that, so late as towards the middle of the last century, Quadrio, one of the most distinguished of them, tells us, that the business of the first quatrain of the sonnet is to state the proposition of it; of the second quatrain to prove the proposition; of the first terzette to confirm it, and of the second terzette to draw the conclusion; 2 and the good Father Ceva, in his selection of pieces of this kind for the use of schools, likens the sonnet to a syllogism, in which, if the conclusion is not strictly drawn from the premises, the whole is a mere play of words and of rhymes. 3  7
  That such a system could never prevail over the manifest temptations to be more free and easy, need hardly be observed. The sonnet was too obvious a resource for expressing any emotion whatsoever, to be restricted to formalities so pedantic; and accordingly it finally obeyed no laws in general but those that are essential to all good poetry, with the exception of such as were necessary to render it what it was, and to secure for it that completeness, and that freedom from blemish, which alone can render a small thing precious.  8
  On the other hand, it would be rash to affirm that logic had no involuntary concern, or music no artistical concern, in forming the sonnet. There is an instinct of music in every kind of verse; and there is, or ought to be, a beginning, a middle, and an end in every kind of composition. Reason must naturally reason, and emotion speak, as well and consistently as it can; and music is only emotion singing. The poets who flourished while the sonnet was maturing were all, more or less, musicians as well as poets; the minstrels, their predecessors, had invariably, in the first instance, written both the words and the music of their compositions, though the tasks gradually became divided; but every poet played on the lute or guitar; every poet accompanied his chant or his recitation with it; and the more musical the poet, the more he would feel the musical capabilities of what he composed. One improvement in this respect would produce another; verses, like musical bars, would be found to have their claims on variety of accent and pause; and final satisfaction of the ear might, naturally enough, suggest the settlement of a determinate amount of size in the sum total. Theories on such points may be pushed to extremes by enthusiasts, and niceties of intention be attributed where they did not exist; but as verse itself is often written without a knowledge of prosody, and music itself composed with little insight into the subtleties of its grammar, so feeling alone might have suggested those analogies of majors and minors, of tones, modulations, cadences, and harmonical progressions, the reality of which in sonnets of masterly execution will be admitted, more or less, by every good ear which is not unacquainted with the terms of the musical art.  9
  A sonnet is, in fact, or ought to be, a piece of music as well as of poetry; and as every lover of music is sensible of the division even of the smallest air into two parts, the second of which is the consequent or necessary demand of the first; and as these parts consist of phrases and cadences, which have similar sequences and demands of their own, so the composition called a sonnet, being a long air or melody, becomes naturally divided into two different strains, each of which is subdivided in like manner; and as quatrains constitute the one strain, and terzettes the other, we are to suppose this kind of musical demand the reason why the limitation to fourteen lines became, not a rule without a reason, but an harmonious necessity.  10
  Readers, however, who may wish to write sonnets at once, notwithstanding they may have had little acquaintance with the art, are not bound to think of all which is here said, or of any portion of it, till the interest they take in their work incite them to do so. Ear and other qualifications may suffice them to begin,—may suffice them always, if excellent; though, in that case, the more they can do, the more they will wish to know what can be done. The greatest poets, as we shall see presently, even in regard to a sonnet, have ever been the greatest students of their art. I do not say that lesser poets, far lesser, cannot study it too. All I say is, that the greatest poets invariably study it; and with results of course in proportion.  11
  The majority of the persons who look into this book will be no “scorners” of sonnets; perhaps none of them will; but should such a person be among them, the following summary of the conditions requisite to a perfect sonnet may show him what he has undertaken to scorn. For a sonnet, like everything else, is to be judged according to what properly and thoroughly constitutes it, and not from specimens that fall short of its requirements. The student need not be alarmed by the summary. Perfection, as a sine qua non, is to be demanded of nobody; and many a sonnet has lasted and been found beautiful, that had no pretensions to it. Still perfection is to be aimed at: it has often, in this small shape, been realized; points of it may be attained, if not all; some points must be always attempted, such as unforced rhymes, and unsuperfluous words; and the student will do well always to bear in mind what has been said by a critic not given to the sentimental,—that “one sonnet without a fault is alone worth a long poem.” 4  12
  The sonnet, then, in order to be a perfect work of art, and no compromise with a difficulty, must in the first place be a Legitimate Sonnet after the proper Italian fashion; that is to say, with but two rhymes to the octave, and not more than three in the sestette.  13
  Secondly, it must confine itself to one leading idea, thought, or feeling.  14
  Thirdly, it must treat this one leading idea, thought, or feeling in such a manner as to leave in the reader’s mind no sense of irrelevancy or insufficiency.  15
  Fourthly, it must not have a speck of obscurity.  16
  Fifthly, it must not have a forced rhyme.  17
  Sixthly, it must not have a superfluous word.  18
  Seventhly, it must not have a word too little; that is to say, an omission of a word or words, for the sake of convenience.  19
  Eighthly, it must not have a word out of its place.  20
  Ninthly, it must have no very long word, or any other that tends to lessen the number of accents, and so weaken the verse.  21
  Tenthly, its rhymes must be properly varied and contrasted, and not beat upon the same vowel,—a fault too common with very good sonnets. It must not say, for instance, rhyme, tide, abide, crime; or play, gain, refrain, way; but contrast i with o, or with some other strongly opposed vowel, and treat every vowel on the same principle.  22
  Eleventhly, its music, throughout, must be as varied as it is suitable; more or less strong, or sweet, according to the subject; but never weak or monotonous, unless monotony itself be the effect intended.  23
  Twelfthly, it must increase, or, at all events, not decline, in interest, to its close.  24
  Lastly, the close must be equally impressive and unaffected; not epigrammatic, unless where the subject warrants it, or where point of that kind is desirable; but simple, conclusive, and satisfactory; strength being paramount, where such elevation is natural, otherwise on a level with the serenity; flowing in calmness, or grand in the manifestation of power withheld.  25
  Go now, you who undertook to scorn the sonnet, and see if you had not better have made yourself a little more acquainted with what you scorned.  26
Note 1. In his collection of sonnets entitled “Laura,” Vol. I., Preface, p. v. [back]
Note 2. Della Storia e della Ragione d’ Ogni Poesia, (Milano, 1742,) Tom. III. p. 16. [back]
Note 3. Scelta di Sonetti, (Torino, 1735,) p. 42. [back]
Note 4. “Un sonnet sans défaut vaut seul un long poëme.”—BOILEAU. [back]


What is ESA?

ESA is an international organisation with 18 Member States. By coordinating the financial and intellectual resources of its members, it can undertake programmes and activities far beyond the scope of any single European country.

What does ESA do?

Who belongs to ESA?

Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United Kingdom. Canada takes part in some projects under a Cooperation agreement. Romania signed its Accession Agreement with ESA on 20 January 2011 and will soon become the 19th Member State.

Where is ESA located?

  • EAC, the European Astronauts Centre in Cologne, Germany;

A new ESA centre has opened in the United Kingdom, at Harwell, Oxfordshire. ESA also has liaison offices in Belgium, USA and Russia; a launch base in French Guiana and ground/tracking stations in various parts of the world.

How many people work for ESA?

There are around 2200 staff working for ESA, from all the Member States and include scientists, engineers, information technology specialists and administrative personnel.

Where do ESA’s funds come from?

How big is ESA’s budget?

ESA's budget for 2011 is €3994 million. ESA operates on the basis of geographical return, i.e. it invests in each Member State, through industrial contracts for space programmes, an amount more or less equivalent to each country’s contribution.

How much does each European spend on ESA?

How does ESA operate?

The Council is ESA's governing body and provides the basic policy guidelines within which ESA develops the European space programme. Each Member State is represented on the Council and has one vote, regardless of its size or financial contribution.

ESA is headed by a Director General who is elected by the Council every four years. Each individual research sector has its own Directorate and reports directly to the Director General. The present Director General of ESA is Jean-Jacques Dordain.

For more information:
Communication Department
European Space Agency
8-10 rue Mario Nikis
75738 Paris
Cedex 15

Tel: + 33 1 5369 7155
Fax: + 33 1 5369 7690


Riviera Maya Destinations

A Diverse and Popular Vacation Destination

The Riviera Maya is a 130 kilometer stretch of Caribbean coastline between the resort city of Cancun in the north and the Mayan ruins of Tulum in the south. Other communities and towns that are part of this famous Mexican beach vacation destination include Puerto Morelos, Playa del Carmen, Cozumel Island, Puerto Aventuras, and Akumal. Being a part of the Yucatan Peninsula, the Riviera Maya has more to offer than its beaches. There is a rich history with many cultural influences and a diverse population. This combination has developed a cosmopolitan feel to the area with a focus on food, activities, shopping and of course, the beach life.

Getting to and around the Riviera Maya

Carretera (highway) 307 is the only highway that runs the length of the Riviera Maya. Small roads on the eastside lead to various beachside resorts, vacation communities, undeveloped beaches and lagoons. The highway continues south to the coastal towns of Mahahual and Xcalak in the Costa Maya. From the highway, a few roads go inland (west) to rural towns, Mayan ruins and fresh water cenotes. The neighboring states of Yucatan and Campeche comprise the western part of the Yucatan Peninsula where colonial towns hold great treasures of culture, history and architecture, different from the Riviera Maya.

Towns and Destinations in the Riviera Maya

Akumal - The Place of the Turtles

Akumal has two names, "The Place of the Turtles" as it is here that you can snorkel with turtles off the beach, and "The Place of Magic" because it magically makes your stress disappear. Located just one hour and ten minutes south of Cancun on the Mexican Caribbean coastline of the Yucatan Peninsula, Akumal is favored vacation spot. The history is vast, its community friendly, and it was one of the first Riviera Maya communities established in the 1960s.

Playa del Carmen - Chic and cosmopolitan

Playa del Carmen is a cosmopolitan city in the heart of the Riviera Maya. A global mix of fun-loving travellers and vacationers gather year round to relax on white sandy beaches, check out the happening night-life and soak up the international atmosphere. ‘Playa’, its local name, boasts stylish beach clubs, great vacation accommodations, excellent amenities and the ferry to Cozumel Island.

Puerto Aventuras - Marina community

There is no place like Puerto Aventuras! Puerto's central location on the Riviera Maya is perfect for excursions to the area’s best sights and activities along the Caribbean coastline, including cenotes for swimming and snorkeling. It’s also just a stone’s throw away from the popular eco-adventure parks of X'caret, Xplor and Xel-Ha for all day entertainment, water sports and fun.

Puerto Morelos - Small fishing village

Puerto Morelos is in the northern part of the Riviera Maya just 20 minutes south of the Cancun International Airport.  With its iconic lighthouse, Puerto Morelos is one of the oldest communities on Mexico's Caribbean coast.  Today, the town is known for its National Marine Park, which is part of the Mesoamerican Barrier Reef. Divers and snorkelers appreciate the beauty of the sea and the friendliness of the community.

Sian Ka'an Biosphere Reserve -WOW!

In the Mayan language, Sian Ka'an means ‘where the sky is born’, or ‘gift from the sky’. The Sian Ka'an Biosphere Reserve is a 1.3 million acre nature reserve just south of Tulum in the Riviera Maya. This protected reserve is inhabited by countless plant species, bird and animals. Add 23 known archaeological sites to the list of attractions and you are bound to have an adventure.

Soliman Bay - Quiet paradise

Perhaps its our romantic memories of the days of old here in Mexico, but Soliman Bay holds a special place in our hearts.  This residential community is where a morning cup of coffee has never tasted finer as you watch the sunrise.  From luxury villas to quaint bungalows and even a stylish boutique hotel, Soliman Bay is paradise for those seeking a peaceful place to relax... and dream.

Tankah Bay - Villas, a cenote and peace

The Tankah area was once nothing more than coconut groves known as "cocals". Today, Tankah is now a residential and vacation villa area minutes from the ruins of Tulum.  Tankah is known for the "Casa Cenote" restaurant where you can grab a bite, swim in the beautiful cenote and enjoy nature.  It's a nice escape for families wanting a place for quality family time.

Tulum - Depth of Mayan history

In ancient times, Tulum served as a point of defence and a port for the thriving maritime commerce. Today, US News Travel calls Tulum the #1 beach in Mexico. The combination of thriving eco-tourism activities, and the only major Mayan ruin found on Mexico's Caribbean coastline makes Tulum a great getaway. Tulum is the ultimate destination for a bohemian style vacation where you can enjoy free and easy days.

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Free Fractal generation using Gnofract 4D - Free Fractal Software

What is fractal

A fractal often has the following features:

  • It has a fine structure at arbitrarily small scales.
  • It has a simple and recursive definition.
Because they appear similar at all levels of magnification, fractals are often considered to be infinitely complex (in informal terms). Natural objects that approximate fractals to a degree include clouds, mountain ranges, lightning bolts, coastlines, and snow flakes. However, not all self-similar objects are fractals—for example, the real line (a straight Euclidean line) is formally self-similar but fails to have other fractal characteristics (Wikipedia).

What is Gnofract 4D?

Gnofract 4D is a free, open source program which allows anyone to create beautiful images called fractals. The images are automatically created by the computer based on mathematical principles. These include the Mandelbrot and Julia sets and many more. You don't need to do any math: you can explore a universe of images just using a mouse. It runs on Unix-based systems such as Linux and FreeBSD and can also be run on Mac OS X.

In short, I believe it's the best fractal package currently available for Linux. It's easy-to-use, fast, and extremely flexible.

More info about Gnofract 4D and download read here.