Diagnostic value of H3F3A mutations in giant cell tumour of bone compared to osteoclast-rich mimics

Driver mutations in the two histone 3.3 (H3.3) genes, H3F3A and H3F3B, were recently identified by whole genome sequencing in 95% of chondroblastoma (CB) and by targeted gene sequencing in 92% of giant cell tumour of bone (GCT). Given the high prevalence of these driver mutations, it may be possible to utilise these alterations as diagnostic adjuncts in clinical practice. Here, we explored the spectrum of H3.3 mutations in a wide range and large number of bone tumours (n 5 412) to determine if these alterations could be used to distinguish GCT from other osteoclast-rich tumours such as aneurysmal bone cyst, nonossifying fibroma, giant cell granuloma, and osteoclast-rich malignant bone tumours and others. In addition, we explored the driver landscape of GCT through whole genome, exome and targeted sequencing (14 gene panel). We found that H3.3 mutations, namely mutations of glycine 34 in H3F3A, occur in 96% of GCT. We did not find additional driver mutations in GCT, including mutations in IDH1, IDH2, USP6, TP53. The genomes of GCT exhibited few somatic mutations, akin to the picture seen in CB. Overall our observations suggest that the presence of H3F3A p.Gly34 mutations does not entirely exclude malignancy in osteoclast-rich tumours. However, H3F3A p.Gly34 mutations appear to be an almost essential feature of GCT that will aid pathological evaluation of bone tumours, especially when confronted with small needle core biopsies. In the absence of H3F3A p.Gly34 mutations, a diagnosis of GCT should be made with caution.

Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone

It is recognized that some mutated cancer genes contribute to the development of many cancer types, whereas others are cancer type specific. For genes that are mutated in multiple cancer classes, mutations are usually similar in the different affected cancer types. Here, however, we report exquisite tumor type specificity for different histone H3.3 driver alterations. In 73 of 77 cases of chondroblastoma (95%), we found p.Lys36Met alterations predominantly encoded in H3F3B, which is one of two genes for histone H3.3. In contrast, in 92% (49/53) of giant cell tumors of bone, we found histone H3.3 alterations exclusively in H3F3A, leading to p.Gly34Trp or, in one case, p.Gly34Leu alterations. The mutations were restricted to the stromal cell population and were not detected in osteoclasts or their precursors. In the context of previously reported H3F3A mutations encoding p.Lys27Met and p.Gly34Arg or p.Gly34Val alterations in childhood brain tumors, a remarkable picture of tumor type specificity for histone H3.3 driver alterations emerges, indicating that histone H3.3 residues, mutations and genes have distinct functions.

Twentieth Century Modern Architecture and the Countryside: Ludwig Mies van der Rohe's design for a country gold clubhouse for the Krefeld Golf Club Association

This paper investigates relationships between modernity and monumentality in the architecture of Ludwig Mies van der Rohe. In his Modern Architecture, the critic and historian Kenneth Frampton separated Mies’ work into two historical periods, 1921-1933 and 1933-1967; the first he entitled ‘Mies van der Rohe and the significance of fact,’ the second ‘Mies van der Rohe and the monumentalisation of technique.’ The two historical periods correspond to two different geopolitical phases of Mies’ career, the first in Weimar Germany the second in the United States. By looking at a number of designs and texts made by Mies in the 1930’s and 1940’s, this essay questions the validity of separating Mies’ architecture into such clear-cut categories, where each one can enjoy a seeming independence from the other. The fulcrum for the discussion is Mies’ design of 1930 for a country golf clubhouse for the industrial town of Krefeld in north-western Germany. Our attention to the golf clubhouse design was prompted by the recent installation (2013), in which a 1-1 model of the design, made primarily from plywood, was erected in a field close the the site of Mies' original proposal.

Windkracht 13 : het potentieel van kleine en middelgrote windturbines in kaart gebracht

In tegenstelling tot fotovoltaïsche systemen van gelijkaardige grootte, maken kleine en middelgrote windturbines in Vlaanderen nog geen deel uit van het vertrouwde energielandschap. Aan de hand van het demo-disseminatieproject Windkracht 13 wil de Universiteit Gent, in samenwerking met Tecnolec en met de steun van het Agentschap Ondernemen, de barrières voor kleine en middelgrote windturbines wegwerken en goede locaties in Vlaanderen in kaart brengen. De knelpunten die kleine en middelgrote windturbines ondervinden, kunnen onderverdeeld worden in vijf afzonderlijke maar toch vaak samenhangende thema’s: juridisch, economisch, ruimtelijk, technisch en sociaal, de zogenaamde JERTS-invalshoeken. Het doel van het Windkracht 13-project is het openbreken van de markt voor kleine en middelgrote windturbines in Vlaanderen, door demo-installaties te plaatsen, te monitoren en de opgedane kennis te verspreiden.

Complex-order forced van der Pol oscillator

In this paper we consider a complex-order forced van der Pol oscillator. The complex derivative Dα1jβ, with α, β ∈ ℝ+, is a generalization of the concept of an integer derivative, where α = 1, β = 0. The Fourier transforms of the periodic solutions of the complex-order forced van der Pol oscillator are computed for various values of parameters such as frequency ω and amplitude b of the external forcing, the damping μ, and parameters α and β. Moreover, we consider two cases: (i) b = 1, μ = {1.0, 5.0, 10.0}, and ω = {0.5, 2.46, 5.0, 20.0}; (ii) ω = 20.0, μ = {1.0, 5.0, 10.0}, and b = {1.0, 5.0, 10.0}. We verified that most of the signal energy is concentrated in the fundamental harmonic ω0. We also observed that the fundamental frequency of the oscillations ω0 varies with α and μ. For the range of tested values, the numerical fitting led to logarithmic approximations for system (7) in the two cases (i) and (ii). In conclusion, we verify that by varying the parameter values α and β of the complex-order derivative in expression (7), we accomplished a very effective way of perturbing the dynamical behavior of the forced van der Pol oscillator, which is no longer limited to parameters b and ω.

Complex order van der Pol oscillator

In this paper a complex-order van der Pol oscillator is considered. The complex derivative Dα±ȷβ , with α,β∈R + is a generalization of the concept of integer derivative, where α=1, β=0. By applying the concept of complex derivative, we obtain a high-dimensional parameter space. Amplitude and period values of the periodic solutions of the two versions of the complex-order van der Pol oscillator are studied for variation of these parameters. Fourier transforms of the periodic solutions of the two oscillators are also analyzed.

Inneming van Tavasthus in Finlant

Täydellinen nimeke: Inneming van Tavasthus in Finlant, door den Graef van Apraxin etc. nevens de groote nederlage der Zweden, met verlies hunner Trommels en Velt tekenen, en een groot getal van Krygs benden; voorgevallen den 6 van Wynmaent 1713 = Tavasthusa in Finlandia expugnata a Comite Apraxino etc. cum magna clade Suecorum, et jactura tympanorum et vexillorum, multarumque copiarum militarium 6 die Oct: an: 1713.

Mare Balticum. Amstelodami, Apud. F. de Wit. ; Nieuwe pascaert van de Oost Zee t Amsterdam Gedruckt by F. de Wit

Pahville liimattu

Nieuwe paskaart voor een gedeelte van de Oost-Zee = Nouvelle carte hydrographique d'une partie de la Mer Baltique = Nya pass cort öfwer yen dehl af Oster-Siöön = The new sea map of the second of the East-Sea

Sisältää myös kartakkeet: Pastkaartje van de Noord Bodem, Suomenlahden itäosa ja Laatokka

Nieuwe paskaart voor een gedeelte van de Oost-Zee = Nouvelle carte hydrographique d'une partie de la Mer Baltique = Nya pass cort öfwer yen dehl af Oster-Siöön = The new sea map of the second of the East-Sea

Sisältää myös kartakkeet: Pastkaartje van de Noord Bodem, Suomenlahden itäosa ja Laatokka