In Alsace , Goethe blossomed. No other landscape has he described as affectionately as the warm, wide Rhine area. The two became close friends, and crucially to Goethe's intellectual development, Herder kindled his interest in Shakespeare , Ossian and in the notion of Volkspoesie folk poetry. On 14 October Goethe held a gathering in his parental home in honour of the first German "Shakespeare Day". His first acquaintance with Shakespeare's works is described as his personal awakening in literature. On a trip to the village Sessenheim , Goethe fell in love with Friederike Brion , in October ,   but, after ten months, terminated the relationship in August At the end of August , Goethe acquired the academic degree of the Lizenziat Licentia docendi in Frankfurt and established a small legal practice.
Although in his academic work he had expressed the ambition to make jurisprudence progressively more humane, his inexperience led him to proceed too vigorously in his first cases, and he was reprimanded and lost further ones. This prematurely terminated his career as a lawyer after only a few months. At this time, Goethe was acquainted with the court of Darmstadt , where his inventiveness was praised. Goethe also pursued literary plans again; this time, his father did not have anything against it, and even helped. Goethe obtained a copy of the biography of a noble highwayman from the German Peasants' War.
In a couple of weeks the biography was reworked into a colourful drama. Goethe could not subsist on being one of the editors of a literary periodical published by Schlosser and Merck.
In May he once more began the practice of law at Wetzlar. In he wrote the book which would bring him worldwide fame, The Sorrows of Young Werther. In later years Goethe would bypass this problem by periodically authorizing "new, revised" editions of his Complete Works. Goethe thus went to live in Weimar , where he remained for the rest of his life and where, over the course of many years, he held a succession of offices, becoming the Duke's friend and chief adviser.
In , Goethe formed a close relationship to Charlotte von Stein , an older, married woman. The intimate bond with von Stein lasted for ten years, after which Goethe abruptly left for Italy without giving his companion any notice. She was emotionally distraught at the time, but they were eventually reconciled. Goethe, aside from official duties, was also a friend and confidant to the Duke, and participated fully in the activities of the court. For Goethe, his first ten years at Weimar could well be described as a garnering of a degree and range of experience which perhaps could be achieved in no other way.
In , when the chancellor of the Duchy's Exchequer left his office, Goethe agreed to act in his place for two and a half years; this post virtually made him prime minister and the principal representative of the Duchy. Daniel Wilson claims that Goethe engaged in negotiating the forced sale of vagabonds, criminals, and political dissidents as part of these activities.
Goethe's journey to the Italian peninsula and Sicily from to was of great significance in his aesthetic and philosophical development. His father had made a similar journey during his own youth, and his example was a major motivating factor for Goethe to make the trip. More importantly, however, the work of Johann Joachim Winckelmann had provoked a general renewed interest in the classical art of ancient Greece and Rome. Thus Goethe's journey had something of the nature of a pilgrimage to it.
During the course of his trip Goethe met and befriended the artists Angelica Kauffman and Johann Heinrich Wilhelm Tischbein , as well as encountering such notable characters as Lady Hamilton and Alessandro Cagliostro see Affair of the Diamond Necklace. He also journeyed to Sicily during this time, and wrote intriguingly that "To have seen Italy without having seen Sicily is to not have seen Italy at all, for Sicily is the clue to everything.
Winckelmann had not recognized the distinctness of the two styles. Goethe's diaries of this period form the basis of the non-fiction Italian Journey.
Italian Journey only covers the first year of Goethe's visit. The remaining year is largely undocumented, aside from the fact that he spent much of it in Venice. This "gap in the record" has been the source of much speculation over the years. In the decades which immediately followed its publication in , Italian Journey inspired countless German youths to follow Goethe's example.
This is pictured, somewhat satirically, in George Eliot 's Middlemarch. Again during the Siege of Mainz he assisted Carl August as a military observer. His written account of these events can be found within his Complete Works. In , Friedrich Schiller wrote to Goethe offering friendship; they had previously had only a mutually wary relationship ever since first becoming acquainted in This collaborative friendship lasted until Schiller's death in On 13 October, Napoleon 's army invaded the town. The French "spoon guards," the least disciplined soldiers, occupied Goethe's house:.
The 'spoon guards' had broken in, they had drunk wine, made a great uproar and called for the master of the house. Goethe's secretary Riemer reports: His dignified figure, commanding respect, and his spiritual mien seemed to impress even them. Late at night they burst into his bedroom with drawn bayonets.
Goethe was petrified, Christiane raised a lot of noise and even tangled with them, other people who had taken refuge in Goethe's house rushed in, and so the marauders eventually withdrew again. It was Christiane who commanded and organized the defense of the house on the Frauenplan. The barricading of the kitchen and the cellar against the wild pillaging soldiery was her work. Goethe noted in his diary: Preservation of the house through steadfastness and luck. August and Ottilie had three children: Christiane von Goethe died in After , Goethe devoted his endeavours primarily to literature.
By , Goethe was on amiable terms with Kaspar Maria von Sternberg. In , having recovered from a near fatal heart illness, Goethe fell in love with Ulrike von Levetzow whom he wanted to marry, but because of the opposition of her mother he never proposed. Their last meeting in Carlsbad on 5 September inspired him to the famous Marienbad Elegy which he considered one of his finest works.
Johann Wolfgang von Goethe
Goethe, now in his seventies, was greatly impressed by the child, leading to perhaps the earliest confirmed comparison with Mozart in the following conversation between Goethe and Zelter:. Mendelssohn was invited to meet Goethe on several later occasions,  and set a number of Goethe's poems to music. In , Goethe died in Weimar of apparent heart failure. His last words, according to his doctor Carl Vogel, were, Mehr Licht!
Eckermann closes his famous work, Conversations with Goethe , with this passage:. The morning after Goethe's death, a deep desire seized me to look once again upon his earthly garment. His faithful servant, Frederick, opened for me the chamber in which he was laid out. Stretched upon his back, he reposed as if asleep; profound peace and security reigned in the features of his sublimely noble countenance. The mighty brow seemed yet to harbour thoughts. I wished for a lock of his hair; but reverence prevented me from cutting it off.
The body lay naked, only wrapped in a white sheet; large pieces of ice had been placed near it, to keep it fresh as long as possible. Frederick drew aside the sheet, and I was astonished at the divine magnificence of the limbs.
The breast was powerful, broad, and arched; the arms and thighs were elegant, and of the most perfect shape; nowhere, on the whole body, was there a trace of either fat or of leanness and decay. A perfect man lay in great beauty before me; and the rapture the sight caused me made me forget for a moment that the immortal spirit had left such an abode. I laid my hand on his heart — there was a deep silence — and I turned away to give free vent to my suppressed tears.
The first production of Richard Wagner 's opera Lohengrin took place in Weimar in The conductor was Franz Liszt , who chose the date 28 August in honour of Goethe, who was born on 28 August Die Leiden des jungen Werthers , which gained him enormous fame as a writer in the Sturm und Drang period which marked the early phase of Romanticism.
Indeed, Werther is often considered to be the "spark" which ignited the movement, and can arguably be called the world's first "best-seller. In the last period, between Schiller's death, in , and his own, appeared Faust Part One , Elective Affinities , the West-Eastern Diwan a collection of poems in the Persian style, influenced by the work of Hafez , his autobiographical Aus meinem Leben: Dichtung und Wahrheit From My Life: Poetry and Truth which covers his early life and ends with his departure for Weimar, his Italian Journey , and a series of treatises on art.
His writings were immediately influential in literary and artistic circles. The short epistolary novel , Die Leiden des jungen Werthers , or The Sorrows of Young Werther , published in , recounts an unhappy romantic infatuation that ends in suicide. Goethe admitted that he "shot his hero to save himself": The novel remains in print in dozens of languages and its influence is undeniable; its central hero, an obsessive figure driven to despair and destruction by his unrequited love for the young Lotte, has become a pervasive literary archetype. The fact that Werther ends with the protagonist's suicide and funeral—a funeral which "no clergyman attended"—made the book deeply controversial upon its anonymous publication, for on the face of it, it appeared to condone and glorify suicide.
Suicide is considered sinful by Christian doctrine: He said he "turned reality into poetry but his friends thought poetry should be turned into reality and the poem imitated. What set Goethe's book apart from other such novels was its expression of unbridled longing for a joy beyond possibility, its sense of defiant rebellion against authority, and of principal importance, its total subjectivity: The next work, his epic closet drama Faust , was completed in stages.
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The first part was published in and created a sensation. Goethe finished Faust Part Two in the year of his death, and the work was published posthumously. Goethe's original draft of a Faust play, which probably dates from —74, and is now known as the Urfaust , was also published after his death. The first operatic version of Goethe's Faust, by Louis Spohr , appeared in The work subsequently inspired operas and oratorios by Schumann , Berlioz , Gounod , Boito , Busoni , and Schnittke as well as symphonic works by Liszt , Wagner , and Mahler. Faust became the ur-myth of many figures in the 19th century.
Later, a facet of its plot, i. In , the world premiere complete production of Faust was staged at the Goetheanum. Goethe's poetic work served as a model for an entire movement in German poetry termed Innerlichkeit "introversion" and represented by, for example, Heine. Goethe's words inspired a number of compositions by, among others, Mozart , Beethoven who idolised Goethe ,  Schubert , Berlioz and Wolf.
Perhaps the single most influential piece is "Mignon's Song" which opens with one of the most famous lines in German poetry, an allusion to Italy: He is also widely quoted. Epigrams such as "Against criticism a man can neither protest nor defend himself; he must act in spite of it, and then it will gradually yield to him", " Divide and rule , a sound motto; unite and lead, a better one", and "Enjoy when you can, and endure when you must", are still in usage or are often paraphrased.
Some well-known quotations are often incorrectly attributed to Goethe. Goethe overcame emotional turmoil, relational conflicts and mood swings through self-reflection, political and scientific work, and writing. To no one was the faculty for so doing more necessary than to me, for by nature I was constantly carried from one extreme to the other".
As to what I have done as a poet, I take no pride in it But that in my century I am the only person who knows the truth in the difficult science of colours—of that, I say, I am not a little proud, and here I have a consciousness of a superiority to many.
Although his literary work has attracted the greatest amount of interest, Goethe was also keenly involved in studies of natural science. Goethe also had the largest private collection of minerals in all of Europe. By the time of his death, in order to gain a comprehensive view in geology, he had collected 17, rock samples. His focus on morphology and what was later called homology influenced 19th century naturalists , although his ideas of transformation were about the continuous metamorphosis of living things and did not relate to contemporary ideas of "transformisme" or transmutation of species.
The elephant's skull that led Goethe to this discovery, and was subsequently named the Goethe Elephant, still exists and is displayed in the Ottoneum in Kassel , Germany. During his Italian journey, Goethe formulated a theory of plant metamorphosis in which the archetypal form of the plant is to be found in the leaf — he writes, "from top to bottom a plant is all leaf, united so inseparably with the future bud that one cannot be imagined without the other".
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The ever-changing display of plant forms, which I have followed for so many years, awakens increasingly within me the notion: The plant forms which surround us were not all created at some given point in time and then locked into the given form, they have been given Goethe's botanical theories were partly based on his gardening in Weimar. Goethe also popularized the Goethe barometer using a principle established by Torricelli. According to Hegel, "Goethe has occupied himself a good deal with meteorology; barometer readings interested him particularly What he says is important: He claims to deduce from it that the barometric level varies in the same proportion not only in each zone but that it has the same variation, too, at different altitudes above sea-level".
In , Goethe published his Theory of Colours , which he considered his most important work. In it, he contentiously characterized colour as arising from the dynamic interplay of light and darkness through the mediation of a turbid medium. After being translated into English by Charles Eastlake in , his theory became widely adopted by the art world, most notably J.
Goethe was vehemently opposed to Newton's analytic treatment of colour, engaging instead in compiling a comprehensive rational description of a wide variety of colour phenomena. Although the accuracy of Goethe's observations does not admit a great deal of criticism, his aesthetic approach did not lend itself to the demands of analytic and mathematical analysis used ubiquitously in modern Science.
Goethe was, however, the first to systematically study the physiological effects of colour, and his observations on the effect of opposed colours led him to a symmetric arrangement of his colour wheel, 'for the colours diametrically opposed to each other Goethe, Theory of Colours , Goethe outlines his method in the essay The experiment as mediator between subject and object Steiner elaborated on that in the books The Theory of Knowledge Implicit in Goethe's World-Conception  and Goethe's World View ,  in which he characterizes intuition as the instrument by which one grasps Goethe's biological archetype— The Typus.
Novalis , himself a geologist and mining engineer, expressed the opinion that Goethe was the first physicist of his time and 'epoch-making in the history of physics', writing that Goethe's studies of light, of the metamorphosis of plants and of insects were indications and proofs 'that the perfect educational lecture belongs in the artist's sphere of work'; and that Goethe would be surpassed 'but only in the way in which the ancients can be surpassed, in inner content and force, in variety and depth—as an artist actually not, or only very little, for his rightness and intensity are perhaps already more exemplary than it would seem'.
Many of Goethe's works, especially Faust , the Roman Elegies , and the Venetian Epigrams , depict erotic passions and acts. For instance, in Faust , the first use of Faust's power after signing a contract with the devil is to seduce a teenage girl. Some of the Venetian Epigrams were held back from publication due to their sexual content. Goethe clearly saw human sexuality as a topic worthy of poetic and artistic depiction, an idea that was uncommon in a time when the private nature of sexuality was rigorously normative.
Goethe wrote of both boys and girls: If I tire of her as a girl, she'll play the boy for me as well" Goethe, What culture has won from nature will not be surrendered or given up at any price. Goethe was a freethinker who believed that one could be inwardly Christian without following any of the Christian churches, many of whose central teachings he firmly opposed, sharply distinguishing between Christ and the tenets of Christian theology, and criticizing its history as a "hodgepodge of fallacy and violence". P-values less than 0. The analysis was performed separately for each factor with the parameters listed in the table being introduced as covariates, respectively.
These patients showed the lowest risk for metachronous metastases formation. Cluster 2 with a low risk for metastasis formation was further characterized by low MACC1 expression. Patients in Cluster 4 had the highest risk for metachronous metastases development. Classification of CRC patients with regard to their molecular characterization.
A Integrative 2-step cluster analyses allowed the differentiation of four clusters with regard to their tumor characteristics. The order of the molecular markers represents the significance of the predictor was determined by the 2- step cluster analysis function. Patients of Cluster 1 had the best prognosis and patients in Cluster 4 had the worst prognosis.
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This exploratory study has limitations especially due to the limited number of patient samples. But this cohort has also several strengths: The marker analyses were performed with microdissected cryosections verified by an experienced pathologist. Furthermore the studied cohort is very well characterized and only samples from preoperatively untreated patients with very long follow-up data and complete clinicopathological information were used.
Therefore, this refinement allows improved individualized prognosis and intervention strategies for the majority of CRC patients in clinical routine. Written informed consent was obtained from the patient for the publication of this report and any accompanying images. Contains the localization of the metachronous, distant metastases of the patients within the cohort.
The frequencies of postoperative treatment within the patient cohort are shown. Includes the univariate and multivariate Cox regression analyses of the analyzed biomarkers.
Katharina Ilm and Wolfgang Kemmner contributed equally to this work. The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. KI and WK contributed equally as first authors.
They performed the analysis, interpreted the results and wrote the manuscript. MO and SB assisted with the statistical analysis and provided critical analysis of the manuscript. GK and PH assisted with performance of mutation and expression analyses. US and PMS designed the study, provided clinical advice and revised the manuscript for important intellectual content.
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All authors critically analyzed, read and approved the final manuscript. Peter M Schlag, Email: National Center for Biotechnology Information , U. Journal List Mol Cancer v. Published online Feb Received Sep 12; Accepted Feb 5. This article has been cited by other articles in PMC. Electronic supplementary material The online version of this article doi: Open in a separate window. Conclusion This exploratory study has limitations especially due to the limited number of patient samples. Consent Written informed consent was obtained from the patient for the publication of this report and any accompanying images.
Additional files Additional file 1: Footnotes Katharina Ilm and Wolfgang Kemmner contributed equally to this work. Competing interests The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. Contributor Information Katharina Ilm, Email: Cancer incidence and mortality worldwide: