Subgroup-specific structural variation across 1,000 medulloblastoma genomes

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4 alpha. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kappa B signalling in Group 4, suggest future avenues for rational, targeted therapy.

Ministerielle Reichsorgel: Orgelspieler: I kann holt ka Harmonie rausbringen ...

Welsch (Projektbearbeiter): Karikatur auf die der Frankfurter Nationalversammlung zuwiderlaufende Politik Friedrich Wilhelms IV. von Preußen: der den Blasebalg tretende und dabei Champagner trinkende König zwingt dem Orgelspieler (Erzherzog Johann) eine wenig harmonische Partitur mit dem Titel "Wir lassen halt Alles beim Alten" auf. Im Hintergrund führende Paulskirchenabgeordnete (u.a. Gagern und Robert Blum) als willenlose Orgelpfeifen

The living plant; a description and interpretation of its functions and structure, by William F. Ganong.

1913

Letters from William Tudor to his family,

Three letters written from Tudor to his family from London. Among the subjects about which he writes include the fruit and vegetable bushes and seeds he is sending to Rockwood, the family estate, as well as his impressions of London society and weather. He also writes about political issues, including the Napoleonic Wars, unification in Ireland, and the challenges of being an American in trade in England.

Letter from William Tudor to his family,

Four letters written from Tudor to his family while he was traveling in France in 1800 and 1802. In two letters, he describes in detail his capture by a French privateer aboard the ship Minerva in the spring of 1800. He also discusses the business activities of "Mr. C" (John Codman), his employer. Tudor additionally describes the French countryside and the impact of the French Revolutionary Wars on the cities.

Letters from William Tudor to his family,

Five letters written from St. Pierre, Martinique, include updates on Tudor’s attempts to secure exclusive commercial rights to import ice to the island, as well as his ideas for storing ice and methods of storing cargo onboard a ship.

Letters from William Tudor to his family,

Two letters written from St. Pierre and Les Trois-Îlets, Martinique; in the latter Tudor discusses the recovery of his cousin and traveling companion James Savage, who had fallen ill. He also describes the conditions of slaves on several local estates and plantations

Letters from William Tudor to his family,

Four letters written from St. Pierre, Martinique, Basseterre, Guadalupe, and St. Barts. In one letter written over a number of days, he describes extensively his travels in Antigua, and the various people he met, including Captain William Jarvis. He also details his meeting with Ralph Payne, 1st Baron Lavington, the governor of the Leeward Islands, regarding the prospects of importing ice.