Somatic mosaicism in Fanconi anemia: Evidence of genotypic reversion in lymphohematopoietic stem cells

Somatic mosaicism has been observed previously in the lymphocyte population of patients with Fanconi anemia (FA). To identify the cellular origin of the genotypic reversion, we examined each lymphohematopoietic and stromal cell lineage in an FA patient with a 2815–2816ins19 mutation in FANCA and known lymphocyte somatic mosaicism. DNA extracted from individually plucked peripheral blood T cell colonies and marrow colony-forming unit granulocyte–macrophage and burst-forming unit erythroid cells revealed absence of the maternal FANCA exon 29 mutation in 74.0%, 80.3%, and 86.2% of colonies, respectively. These data, together with the absence of the FANCA exon 29 mutation in Epstein–Barr virus-transformed B cells and its presence in fibroblasts, indicate that genotypic reversion, most likely because of back mutation, originated in a lymphohematopoietic stem cell and not solely in a lymphocyte population. Contrary to a predicted increase in marrow cellularity resulting from reversion in a hematopoietic stem cell, pancytopenia was progressive. Additional evaluations revealed a partial deletion of 11q in 3 of 20 bone marrow metaphase cells. By using interphase fluorescence in situ hybridization with an MLL gene probe mapped to band 11q23 to identify colony-forming unit granulocyte–macrophage and burst-forming unit erythroid cells with the 11q deletion, the abnormal clone was exclusive to colonies with the FANCA exon 29 mutation. Thus, we demonstrate the spontaneous genotypic reversion in a lymphohematopoietic stem cell. The subsequent development of a clonal cytogenetic abnormality in nonrevertant cells suggests that ex vivo correction of hematopoietic stem cells by gene transfer may not be sufficient for providing life-long stable hematopoiesis in patients with FA.

Linguistic aspects of speech synthesis.

The conversion of text to speech is seen as an analysis of the input text to obtain a common underlying linguistic description, followed by a synthesis of the output speech waveform from this fundamental specification. Hence, the comprehensive linguistic structure serving as the substrate for an utterance must be discovered by analysis from the text. The pronunciation of individual words in unrestricted text is determined by morphological analysis or letter-to-sound conversion, followed by specification of the word-level stress contour. In addition, many text character strings, such as titles, numbers, and acronyms, are abbreviations for normal words, which must be derived. To further refine these pronunciations and to discover the prosodic structure of the utterance, word part of speech must be computed, followed by a phrase-level parsing. From this structure the prosodic structure of the utterance can be determined, which is needed in order to specify the durational framework and fundamental frequency contour of the utterance. In discourse contexts, several factors such as the specification of new and old information, contrast, and pronominal reference can be used to further modify the prosodic specification. When the prosodic correlates have been computed and the segmental sequence is assembled, a complete input suitable for speech synthesis has been determined. Lastly, multilingual systems utilizing rule frameworks are mentioned, and future directions are characterized.

Eukaryotic methionyl aminopeptidases: two classes of cobalt-dependent enzymes.

Using partial amino acid sequence data derived from porcine methionyl aminopeptidase (MetAP; methionine aminopeptidase, peptidase M; EC 3.4.11.18), a full-length clone of the homologous human enzyme has been obtained. The cDNA sequence contains 2569 nt with a single open reading frame corresponding to a protein of 478 amino acids. The C-terminal portion representing the catalytic domain shows limited identity with MetAP sequences from various prokaryotes and yeast, while the N terminus is rich in charged amino acids, including extended strings of basic and acidic residues. These highly polar stretches likely result in the spuriously high observed molecular mass (67 kDa). This cDNA sequence is highly similar to a rat protein, termed p67, which was identified as an inhibitor of phosphorylation of initiation factor eIF2 alpha and was previously predicted to be a metallopeptidase based on limited sequence homology. Model building established that human MetAP (p67) could be readily accommodated into the Escherichia coli MetAP structure and that the Co2+ ligands were fully preserved. However, human MetAP was found to be much more similar to a yeast open reading frame that differed markedly from the previously reported yeast MetAP. A similar partial sequence from Methanothermus fervidus suggests that this p67-like sequence is also found in prokaryotes. These findings suggest that there are two cobalt-dependent MetAP families, presently composed of the prokaryote and yeast sequences (and represented by the E. coli structure) (type I), on the one hand, and by human MetAP, the yeast open reading frame, and the partial prokaryotic sequence (type II), on the other.

Modeling a mobile robot using a grammatical model

Virtual Worlds Generator is a grammatical model that is proposed to define virtual worlds. It integrates the diversity of sensors and interaction devices, multimodality and a virtual simulation system. Its grammar allows the definition and abstraction in symbols strings of the scenes of the virtual world, independently of the hardware that is used to represent the world or to interact with it. A case study is presented to explain how to use the proposed model to formalize a robot navigation system with multimodal perception and a hybrid control scheme of the robot.

A grammatical approach to the modeling of an autonomous robot

Virtual Worlds Generator is a grammatical model that is proposed to define virtual worlds. It integrates the diversity of sensors and interaction devices, multimodality and a virtual simulation system. Its grammar allows the definition and abstraction in symbols strings of the scenes of the virtual world, independently of the hardware that is used to represent the world or to interact with it. A case study is presented to explain how to use the proposed model to formalize a robot navigation system with multimodal perception and a hybrid control scheme of the robot. The result is an instance of the model grammar that implements the robotic system and is independent of the sensing devices used for perception and interaction. As a conclusion the Virtual Worlds Generator adds value in the simulation of virtual worlds since the definition can be done formally and independently of the peculiarities of the supporting devices.

On a conjecture of Lapidus and van Frankenhuysen

In this paper it is shown that a conjecture of Lapidus and van Frankenhuysen of 2003 on the existence of a vertical line such that the density of the complex dimensions of nonlattice fractal strings with M scaling ratios off this line vanishes in the limit as M→∞, fails on the class of nonlattice self-similar fractal strings.

Nord Stream expansion: what does it mean for Europe? EPC Commentary, 2 July 2015

Two announcements in sequence have shaken the energy debate on 18 and 19 June. Gazprom announced the signature of a Memorandum of Understanding with Shell, Exon and OMV for the construction of strings 3 and 4 of Nord Stream, aiming at doubling the current 55 bcm capacity of the corridor running in the Baltic sea bed and connecting the Russian terminal of Vyborg to Germany. On the day after, a €2 bn deal between Russia and Greece was signed for extending the Turkish Stream project into Greek territory. ...

Pastorale aus der Weihnachtsmusik (Concerto grosso Nr. 8) für 1 Violine (2 Violinen) Klavier

Originally for 2 violins, violoncello, strings, and cembalo.

Brandenburg concerto no. 5 in D major. [music] /

For flute, violin, harpsicord (cembalo concertato) and strings.

Quartette für Streichinstrumente.

Includes Divertimenti for strings, K. 125a-125c (136-138), Adagio und Fuge, for strings, K. 546, Quartets for flute and strings, K. 285 and 298, and Quartet for oboe and strings, K. 368b (370)

Composizioni /

Mode of access: Internet.

5 sinfonia [!] /

No. 2 not included in Mennicke's thematic list.

Practical instrumentation /

Pt. 1. The strings.--Pt. 2. The wood-wind.--Pt. 3. Strings and wood-wind combined.--Pt. 4. The horns.--Pt. 5. The combination of strings, wood-wind and horns.--Pt. 6. The trumpets, cornets, trombones, tubas and instruments of percussion.--Pt. 7. Harp, mandoline, zither, guitar, piano (cembalo), organ and harmonium.

Marche élégiaque : pour orgue, instruments à cordes et deux hautbois (ad libitum) : op. 74 /

For organ, strings, and 2 oboes (optional).

Passionsmusiken

The 1st work for 5 voices (cantus, altus, tenor 1 and 2, bassus) strings, and continuo. The 2d, for 5 voices (canto 1 and 2, alto, tenore, basso) strings, and continuo. The continuo parts are realized for organ.