Genetic analysis of the Linnaean Ulva lactuca (Ulvales, Chlorophyta) holotype and related type specimens reveals name misapplications, unexpected origins, and new synonymies.

Current usage of the name Ulva lactuca, the generitype of Ulva, remains uncertain. Genetic analyses were performed on the U. lactuca Linnaean holotype, the U. fasciata epitype, the U. fenestrata holotype, the U. lobata lectotype, and the U. stipitata lectotype. The U. lactuca holotype is nearly identical in rbcL sequence to the U. fasciata epitype, a warm temperate to tropical species, rather than the cold temperate species to which the name U. lactuca has generally been applied. We hypothesize that the holotype specimen of U. lactuca came from the Indo-Pacific rather than northern Europe. Our analyses indicate that U. fasciata and U. lobata are heterotypic synonyms of U. lactuca. Ulva fenestrata is the earliest name for northern hemisphere, cold temperate Atlantic and Pacific species, with U. stipitata a junior synonym. DNA sequences from type specimens provide an unequivocal method for applying names to Ulva species. This article is protected by copyright. All rights reserved

On the analysis of sedimentation velocity in the study of protein complexes

Sedimentation velocity analytical ultracentrifugation has experienced a significant transformation, precipitated by the possibility of efficiently fitting Lamm equation solutions to the experimental data. The precision of this approach depends on the ability to account for the imperfections of the experiment, both regarding the sample and the instrument. In the present work, we explore in more detail the relationship between the sedimentation process, its detection, and the model used in the mathematical data analysis. We focus on configurations that produce steep and fast-moving sedimentation boundaries, such as frequently encountered when studying large multi-protein complexes. First, as a computational tool facilitating the analysis of heterogeneous samples, we introduce the strategy of partial boundary modeling. It can simplify the modeling by restricting the direct boundary analysis to species with sedimentation coefficients in a predefined range. Next, we examine factors related to the experimental detection, including the magnitude of optical aberrations generated by out-of-focus solution columns at high protein concentrations, the relationship between the experimentally recorded signature of the meniscus and the meniscus parameter in the data analysis, and the consequences of the limited radial and temporal resolution of the absorbance optical scanning system. Surprisingly, we find that large errors can be caused by the finite scanning speed of the commercial absorbance optics, exceeding the statistical errors in the measured sedimentation coefficients by more than an order of magnitude. We describe how these effects can be computationally accounted for in SEDFIT and SEDPHAT

An all silicon quantum computer

A solid-state implementation of a quantum computer composed entirely of silicon is proposed. Qubits are Si-29 nuclear spins arranged as chains in a Si-28 (spin-0) matrix with Larmor frequencies separated by a large magnetic field gradient. No impurity dopants or electrical contacts are needed. Initialization is accomplished by optical pumping, algorithmic cooling, and pseudo-pure state techniques. Magnetic resonance force microscopy is used for readout. This proposal takes advantage of many of the successful aspects of solution NMR quantum computation, including ensemble measurement, RF control, and long decoherence times, but it allows for more qubits and improved initialization.Comment: ReVTeX 4, 5 pages, 2 figure

On computational approaches for size-and-shape distributions from sedimentation velocity analytical ultracentrifugation

Sedimentation velocity analytical ultracentrifugation has become a very popular technique to study size distributions and interactions of macromolecules. Recently, a method termed two-dimensional spectrum analysis (2DSA) for the determination of size-and-shape distributions was described by Demeler and colleagues (Eur Biophys J 2009). It is based on novel ideas conceived for fitting the integral equations of the size-and-shape distribution to experimental data, illustrated with an example but provided without proof of the principle of the algorithm. In the present work, we examine the 2DSA algorithm by comparison with the mathematical reference frame and simple well-known numerical concepts for solving Fredholm integral equations, and test the key assumptions underlying the 2DSA method in an example application. While the 2DSA appears computationally excessively wasteful, key elements also appear to be in conflict with mathematical results. This raises doubts about the correctness of the results from 2DSA analysis

TBCRC 008: Early Change in 18F-FDG Uptake on PET Predicts Response to Preoperative Systemic Therapy in Human Epidermal Growth Factor Receptor 2-Negative Primary Operable Breast Cancer

Epigenetic modifiers, including the histone deacetylase inhibitor vorinostat, may sensitize tumors to chemotherapy and enhance outcomes. We conducted a multicenter randomized phase II neo-adjuvant trial of carboplatin and nanoparticle albumin-bound paclitaxel (CP) with vorinostat or placebo in women with stage II/III, human epidermal growth factor receptor 2 (HER2)–negative breast cancer, in which we also examined whether change in maximum standardized uptake values corrected for lean body mass (SULmax) on 18F-FDG PET predicted pathologic complete response (pCR) in breast and axillary lymph nodes

Currículo de la pre secundaria en Timor Oriental y su articulación con la secundaria general

Problemas herdados nas últimas décadas conduziram Timor-Leste a reestruturar os currículos do ensino pré-secundário – EPS – e do secundário geral – ESG.1 Atendendo à importância de uma adequada articulação vertical ao longo dos ciclos de escolaridade e diante do cumprimento de uma primeira edição completa do EPS, importa estudar se tal currículo está alinhado com o do ESG, em particular no que respeita às Ciências e Tecnologia. Este artigo centra-se na análise do currículo do EPS e na avaliação da sua articulação com o do ESG. Não obstante existam décalages entre o currículo prescrito, o implementado e o apropriado, é relevante haver sintonia no nível dos currículos para uma educação e formação de boa qualidade, fundamentais à consecução dos Objetivos de Desenvolvimento do Milénio.Problems inherited from the last decades have led Timor-Leste to restructure its pre-secondary – EPS – and general secondary – ESG – curricula. Considering the importance of an adequate vertical articulation throughout the schooling cycles and before the conclusion of the first complete edition of the EPS, it is necessary to study if such a curriculum is aligned with the one of the ESG, in particular with regard to Science and Technology. This article focuses on the analysis of the EPS curriculum and the evaluation of its articulation with the one of ESG. Notwithstanding the décalages among the prescribed, the implemented and the appropriate curricula, it is relevant to have a fine-tuning at this level to ensure good quality education and training, essential to achieve the millennium development goals.Des problèmes hérités des dernières décennies ont conduit le Timor-Oriental à restructurer ses programmes d’enseignement présecondaire – EPS –, ainsi que ceux de l’enseignement secondaire général – ESG. Compte tenu de l’importance d’une bonne articulation verticale tout au long des cycles scolaires etvu qu’une première édition complète de l’EPS a déjà été mise en place, il est important de vérifier si ce programme s’aligne bien à celui de l’ESG, particulièrement en ce qui concerne les Sciences et la Technologie. Cet article se concentre sur l’analyse du programme de l’EPS et sur l’évaluation de son articulation avec celui de l’ESG. Nonobstant certains décalages entre le programme prescrit, celui qui a été mis en œuvre et celui qui est approprié, il est nécessaire que les programmes soient en phase pour atteindre une éducation et une formation de qualité, fondamentales pour la réalisation des Objectifs du Millénaire pour le Développement.Problemas heredados en las últimas décadas hicieron que Timor Oriental reestructurase los currículos de la educación pre secundaria – EPS – y de la secundaria general – ESG. En función de la importancia de una adecuada articulación vertical a lo largo de los ciclos de escolaridad y frente al cumplimiento de una primera edición completa do EPS, importa estudiar si tal currículo está alineado con el del ESG, en particular en lo que concierne a las Ciencias y Tecnología. Este artículo se centra en el análisis del currículo del EPS y en la evaluación de su articulación con el del ESG. No obstante la existencia de décalages entre el currículo prescrito, el implementado y el apropiado, es relevante que haya sintonía a nivel de los currículos para una educación y formación de calidad, fundamentales para la consecución de los Objetivos de Desarrollo del Milenio

PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1

Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD > 2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.Peer reviewe

Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel

To date, most BC GWASs have been performed Background Polygenic risk score (PRS), calculated in individuals of European (EUR) ancestry, and based on genome-wide association studies (GWASs), the generalisation of EUR-based PRS to other can improve breast cancer (BC) risk assessment. populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women. Methods We generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel. Results In the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28). Conclusions Extant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women

Inhibition of Hedgehog Signaling Decreases Proliferation and Clonogenicity of Human Mesenchymal Stem Cells

Human mesenchymal stem cells (hMSC) have the ability to differentiate into osteoblasts, adipocytes and chondrocytes. We have previously shown that hMSC were endowed with a basal level of Hedgehog signaling that decreased after differentiation of these cells. Since hMSC differentiation is associated with growth-arrest we investigated the function of Hh signaling on cell proliferation. Here, we show that inhibition of Hh signaling, using the classical inhibitor cyclopamine, or a siRNA directed against Gli-2, leads to a decrease in hMSC proliferation. This phenomenon is not linked to apoptosis but to a block of the cells in the G0/G1 phases of the cell cycle. At the molecular level, it is associated with an increase in the active form of pRB, and a decrease in cyclin A expression and MAP kinase phosphorylation. Inhibition of Hh signaling is also associated with a decrease in the ability of the cells to form clones. By contrast, inhibition of Hh signaling during hMSC proliferation does not affect their ability to differentiate. This study demonstrates that hMSC are endowed with a basal Hedgehog signaling activity that is necessary for efficient proliferation and clonogenicity of hMSC. This observation unravels an unexpected new function for Hedgehog signaling in the regulation of human mesenchymal stem cells and highlights the critical function of this morphogen in hMSC biology