Microbial communities and malt quality of durum wheat used in brewing

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Genome-wide association study of susceptibility loci for breast cancer in Sardinian population

Abstract Background Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. Methods We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. Results Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p < 10−6 level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10−5, we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16x10−5), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts. Conclusions This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population

Genome-wide association study of susceptibility loci for breast cancer in Sardinian population.

BACKGROUND: Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. METHODS: We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. RESULTS: Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p <  0(-6) level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10(-5), we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16 x 10(-5)), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts. CONCLUSIONS: This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population

A role of BRCA1 and BRCA2 germline mutations in breast cancer susceptibility within Sardinian population

<p>Abstract</p> <p>Background</p> <p>In recent years, numerous studies have assessed the prevalence of germline mutations in <it>BRCA1 </it>and <it>BRCA2 </it>genes in various cohorts. We here extensively investigated the prevalence and geographical distribution of <it>BRCA1-2 </it>mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence of <it>BRCA1-2 </it>germline mutations was also evaluated.</p> <p>Methods</p> <p>Three hundred and forty-eight breast cancer patients presenting a familial recurrence of invasive breast or ovarian carcinoma with at least two affected family members were screened for <it>BRCA1-2 </it>mutations by DHPLC analysis and DNA sequencing. Association of <it>BRCA1 </it>and <it>BRCA2 </it>mutational status with clinical and pathological parameters was evaluated by Pearson's Chi-Squared test.</p> <p>Results and Conclusion</p> <p>Overall, 8 <it>BRCA1 </it>and 5 <it>BRCA2 </it>deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found in <it>BRCA2 </it>gene. The geographical distribution of <it>BRCA1-2 </it>mutations was related to three specific large areas of Sardinia, reflecting its ancient history: <it>a</it>) the Northern area, linguistically different from the rest of the island (where a <it>BRCA2 c.8764_8765delAG </it>mutation with founder effect was predominant); <it>b</it>) the Middle area, land of the ancient Sardinian population (where <it>BRCA2 </it>mutations are still more common than <it>BRCA1 </it>mutations); and <it>c</it>) the South-Western area, with many Phoenician and Carthaginian locations (where <it>BRCA1 </it>mutations are prevalent). We also found that phenotypic features such as high tumor grading and lack of expression of estrogen/progesterone receptors together with age at diagnosis and presence of ovarian cancer in the family may be predictive for the presence of <it>BRCA1-2 </it>germline mutations.</p

A Role of <i>BRCA1</i> and <i>BRCA2</i> germline mutations in breast cancer susceptibility within Sardinian population

Background. In recent years, numerous studies have assessed the prevalence of germline mutations in BRCA1 and BRCA2 genes in various cohorts. We here extensively investigated the prevalence and geographical distribution of BRCA1-2 mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence of BRCA1-2 germline mutations was also evaluated. Methods. Three hundred and forty-eight breast cancer patients presenting a familial recurrence of invasive breast or ovarian carcinoma with at least two affected family members were screened for BRCA1-2 mutations by DHPLC analysis and DNA sequencing. Association of BRCA1 and BRCA2 mutational status with clinical and pathological parameters was evaluated by Pearson's Chi-Squared test. Results and Conclusion. Overall, 8 BRCA1 and 5 BRCA2 deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found in BRCA2 gene. The geographical distribution of BRCA1-2 mutations was related to three specific large areas of Sardinia, reflecting its ancient history: a) the Northern area, linguistically different from the rest of the island (where a BRCA2 c.8764_8765delAG mutation with founder effect was predominant); b) the Middle area, land of the ancient Sardinian population (where BRCA2 mutations are still more common than BRCA1 mutations); and c) the South-Western area, with many Phoenician and Carthaginian locations (where BRCA1 mutations are prevalent). We also found that phenotypic features such as high tumor grading and lack of expression of estrogen/progesterone receptors together with age at diagnosis and presence of ovarian cancer in the family may be predictive for the presence of BRCA1-2 germline mutations

Automatische Modellierung von Manhattan-World Innenräumen aus Laser-Scanner-Daten

Three-dimensional modeling has always received a great deal of attention from computer graphics designers and with emphasis on existing urban scenarios it became an important topic for the photogrammetric community and architects as well. The generation of three-dimensional models of real objects requires both efficient techniques to acquire visual information about the object characteristics and robust methods to compute the mathematical models in which this information can be stored. Photogrammetric techniques for measuring object features recover three-dimensional object profiles from conventional intensity images. Active sensors based on laser measurements are able to directly deliver three-dimensional point coordinates of an object providing a fast and reliable description of its geometric characteristics. In order to transform laser range data into consistent object models, existing CAD software products establish a valid support to manual based approaches. However, the growing use of three-dimensional models in different field of applications brings into focus the need for automated methods for the generation of models. The goal of this thesis is the development of a new concept for the automatic computation of three-dimensional building models from laser data. The automatic modeling method aims at a reconstruction targeted on building interiors with an orthogonal layout. For this purpose, two aspects are considered: the extraction of all surfaces that enclose the interior volume and the computation of the floor plan. As a final result, the three-dimensional model integrates geometry and topology of the interior in terms of its boundary representation. The main idea underlying the automatic modeling is based on plane sweeping, a technique referable to the concept of sweep representation used in computer graphics to generate solid models. A data segmentation driven by the sweep and controlled by a hypothesis-and-test approach allows to assign each laser point to a surface of the building interior. At the next step of the algorithm, the floor plan is recovered by cell decomposition based on split and merge. For a successful generation of the model every activity of the reconstruction workflow should be taken into consideration. This includes the acquisition of the laser data, the registration of the point clouds, the computation of the model and the visualization of the results. The dissertation provides a full implementation of all activities of the automatic modeling pipeline. Besides, due to the high degree of automation, it aims at contributing to the dissemination of three-dimensional models in different areas and in particular in BIM processes for architecture applications.Die dreidimensionale Modellierung erhielt seit jeher große Aufmerksamkeit von Computergrafikdesignern und wurde zudem mit der Verbreitung urbaner Szenarien zu einem wichtigen Gegenstand für die photogrammetrische Gemeinde und für Architekten. Zur Erzeugung dreidimensionaler Modelle realer Objekte werden sowohl effiziente Verfahren zur Erhebung visueller Informationen benötigt als auch robuste Methoden zur Berechnung der mathematischen Modelle, in denen diese Informationen gespeichert werden können. Photogrammetische Methoden für die Erfassung von Objektmerkmalen erzeugen dreidimensionale Objektprofile aus herkömmlichen Bildern, die sich aus Intensitätswerten zusammensetzen. Aktive Sensoren, in Form von Laserscannern, ermöglichen es direkt dreidimensionale Punktkoordinaten eines Objekts zu erheben und damit eine Beschreibung seiner geometrischen Eigenschaften schnell und zuverlässig bereitzustellen. Die Überführung der Laserdaten in konsistente Objektmodelle führt mit bestehenden CAD-Softwareprodukten zu manuellem Aufwand. Jedoch erfordert die zunehmende Verwendung dreidimensionaler Modelle in unterschiedlichen Anwendungsdomänen automatisierte Methoden zur Erzeugung dieser Modelle. Das Ziel dieser Arbeit besteht darin, ein neues Konzept zur automatischen Erzeugung dreidimensionaler Modelle aus Laserdaten zu entwickeln. Die automatische Modellierungsmethode zielt auf die Rekonstruktion von Innenräumen mit orthogonalem Grundriss ab. Dazu werden zwei Aspekte betrachtet: die Extraktion aller Oberflächen, welche den Innenraum umgeben, und die Berechnung des Grundrisses. Als Ergebnis umfasst das dreidimensionale Modell die Geometrie und Topologie des Innenraums in Form eines B-rep. Der zugrundeliegende Ansatz der automatischen Modellierung basiert auf einem Plane-Sweep, der vergleichbar mit der in der Computergrafik verwendeten Sweep-Darstellung von Festkörpermodellen ist. Eine Datensegmentierung, die mittels des Sweeps und eines Hypothese-und-Test-Ansatzes durchgeführt wird, ermöglicht es jeden Laserpunkt einer Oberfläche des Innenraums zuzuweisen. Danach wird der Grundriss mittels einer Zellzerlegung basierend auf einem Split-and-Merge-Ansatz ermittelt. Zur erfolgreichen Erzeugung von Modellen ist jede Aktivität des Rekonstruktionsprozesses zu berücksichtigen. Dieser umfasst die Erhebung der Laserdaten, die Identifikation der Punktwolken, die Berechnung des Models und die Visualisierung des Ergebnisses. Diese Arbeit stellt die komplette Umsetzung aller Aktivitäten des automatisierten Modellierungsprozesses vor. Darüber hinaus wird durch die Erhöhung des Automatisierungsgrades die weitere Verbreitung dreidimensionaler Modelle in verschiedene Domänen insbesondere in BIM-Prozessen für Architekturanwendungen angestrebt