University of Houston

A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients’ lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology. The Cancer Genome Atlas (TCGA) project reports here its analysis of messenger RNA and microRNA expression, promoter methylation, DNA copy number and exome sequences in 489 high-grade serous ovarian adenocarcinomas. The analyses help establish new tumour subtypes. Among other insights is the finding that while the gene encoding p53 tumour suppressor is mutated in almost all tumours, nine other loci including NF1, BRCA1, BRCA2, RB1 and CDK12 carry recurrent albeit low-prevalence mutations. Homologous recombination is defective in about half of the tumours studied, and Notch and FOXM1 signalling are involved in the pathophysiology.

The main purpose of this article is to present several new statistical tests of neutrality of mutations against a class of alternative models, under which DNA polymorphisms tend to exhibit excesses of rare alleles or young mutations. Another purpose is to study the powers of existing and newly developed tests and to examine the detailed pattern of polymorphisms under population growth, genetic hitchhiking and background selection. It is found that the polymorphic patterns in a DNA sample under logistic population growth and genetic hitchhiking are very similar and that one of the newly developed tests, Fs, is considerably more powerful than existing tests for rejecting the hypothesis of neutrality of mutations. Background selection gives rise to quite different polymorphic patterns than does logistic population growth or genetic hitchhiking, although all of them show excesses of rare alleles or young mutations. We show that Fu and Li's tests are among the most powerful tests against background selection. Implications of these results are discussed.

A stable and reproducible superconductivity transition between 80 and 93 K has been unambiguously observed both resistively and magnetically in a new Y-Ba-Cu-0 compound system at ambient pressure. An estimated upper critical field H, 2(0) between 80 and 180 T was obtained.

The authors provide a basic set of guidelines and recommendations for information that should be included in any manuscript that has confirmatory factor analysis or structural equation modeling as the primary statistical analysis technique. The authors provide an introduction to both techniques, along with sample analyses, recommendations for reporting, evaluation of articles in The Journal of Educational Research using these techniques, and concluding remarks.

The ability to detect and accurately estimate the strength of interaction effects are critical issues that are fundamental to social science research in general and IS research in particular. Within the IS discipline, a significant percentage of research has been devoted to examining the conditions and contexts under which relationships may vary, often under the general umbrella of contingency theory (cf. McKeen et al. 1994, Weill and Olson 1989). In our survey of such studies, the majority failed to either detect or provide an estimate of the effect size. In cases where effect sizes are estimated, the numbers are generally small. These results have led some researchers to question both the usefulness of contingency theory and the need to detect interaction effects (e.g., Weill and Olson 1989). This paper addresses this issue by providing a new latent variable modeling approach that can give more accurate estimates of interaction effects by accounting for the measurement error that attenuates the estimated relationships. The capacity of this approach at recovering true effects in comparison to summated regression is demonstrated in a Monte Carlo study that creates a simulated data set in which the underlying true effects are known. Analysis of a second, empirical data set is included to demonstrate the technique's use within IS theory. In this second analysis, substantial direct and interaction effects of enjoyment on electronic-mail adoption are shown to exist.

Considerable confusion surrounds the longstanding question of what constitutes a vortex, especially in a turbulent flow. This question, frequently misunderstood as academic, has recently acquired particular significance since coherent structures (CS) in turbulent flows are now commonly regarded as vortices. An objective definition of a vortex should permit the use of vortex dynamics concepts to educe CS, to explain formation and evolutionary dynamics of CS, to explore the role of CS in turbulence phenomena, and to develop viable turbulence models and control strategies for turbulence phenomena. We propose a definition of a vortex in an incompressible flow in terms of the eigenvalues of the symmetric tensor ${\bm {\cal S}}^2 + {\bm \Omega}^2$ ; here ${\bm {\cal S}}$ and ${\bm \Omega}$ are respectively the symmetric and antisymmetric parts of the velocity gradient tensor ${\bm \Delta}{\bm u}$ . This definition captures the pressure minimum in a plane perpendicular to the vortex axis at high Reynolds numbers, and also accurately defines vortex cores at low Reynolds numbers, unlike a pressure-minimum criterion. We compare our definition with prior schemes/definitions using exact and numerical solutions of the Euler and Navier–Stokes equations for a variety of laminar and turbulent flows. In contrast to definitions based on the positive second invariant of ${\bm \Delta}{\bm u}$ or the complex eigenvalues of ${\bm \Delta}{\bm u}$ , our definition accurately identifies the vortex core in flows where the vortex geometry is intuitively clear.

AUTORES: Daniel J Klionsky1745,1749*, Kotb Abdelmohsen840, Akihisa Abe1237, Md Joynal Abedin1762, Hagai Abeliovich425,
\nAbraham Acevedo Arozena789, Hiroaki Adachi1800, Christopher M Adams1669, Peter D Adams57, Khosrow Adeli1981,
\nPeter J Adhihetty1625, Sharon G Adler700, Galila Agam67, Rajesh Agarwal1587, Manish K Aghi1537, Maria Agnello1826,
\nPatrizia Agostinis664, Patricia V Aguilar1960, Julio Aguirre-Ghiso784,786, Edoardo M Airoldi89,422, Slimane Ait-Si-Ali1376,
\nTakahiko Akematsu2010, Emmanuel T Akporiaye1097, Mohamed Al-Rubeai1394, Guillermo M Albaiceta1294,
\nChris Albanese363, Diego Albani561, Matthew L Albert517, Jesus Aldudo128, Hana Alg€ul1164, Mehrdad Alirezaei1198,
\nIraide Alloza642,888, Alexandru Almasan206, Maylin Almonte-Beceril524, Emad S Alnemri1212, Covadonga Alonso544,
\nNihal Altan-Bonnet848, Dario C Altieri1205, Silvia Alvarez1497, Lydia Alvarez-Erviti1395, Sandro Alves107,
\nGiuseppina Amadoro860, Atsuo Amano930, Consuelo Amantini1554, Santiago Ambrosio1458, Ivano Amelio756,
\nAmal O Amer918, Mohamed Amessou2089, Angelika Amon726, Zhenyi An1538, Frank A Anania291, Stig U Andersen6,
\nUsha P Andley2079, Catherine K Andreadi1690, Nathalie Andrieu-Abadie502, Alberto Anel2027, David K Ann58,
\nShailendra Anoopkumar-Dukie388, Manuela Antonioli832,858, Hiroshi Aoki1791, Nadezda Apostolova2007,
\nSaveria Aquila1500, Katia Aquilano1876, Koichi Araki292, Eli Arama2098, Agustin Aranda456, Jun Araya591,
\nAlexandre Arcaro1472, Esperanza Arias26, Hirokazu Arimoto1225, Aileen R Ariosa1749, Jane L Armstrong1930,
\nThierry Arnould1773, Ivica Arsov2120, Katsuhiko Asanuma675, Valerie Askanas1924, Eric Asselin1867, Ryuichiro Atarashi794,
\nSally S Atherton369, Julie D Atkin713, Laura D Attardi1131, Patrick Auberger1787, Georg Auburger379, Laure Aurelian1727,
\nRiccardo Autelli1992, Laura Avagliano1029,1755, Maria Laura Avantaggiati364, Limor Avrahami1166, Suresh Awale1986,
\nNeelam Azad404, Tiziana Bachetti568, Jonathan M Backer28, Dong-Hun Bae1933, Jae-sung Bae677, Ok-Nam Bae409,
\nSoo Han Bae2117, Eric H Baehrecke1729, Seung-Hoon Baek17, Stephen Baghdiguian1368,
\nAgnieszka Bagniewska-Zadworna2, Hua Bai90, Jie Bai667, Xue-Yuan Bai1133, Yannick Bailly884,
\nKithiganahalli Narayanaswamy Balaji473, Walter Balduini2002, Andrea Ballabio316, Rena Balzan1711, Rajkumar Banerjee239,
\nG abor B anhegyi1052, Haijun Bao2109, Benoit Barbeau1363, Maria D Barrachina2007, Esther Barreiro467, Bonnie Bartel997,
\nAlberto Bartolom e222, Diane C Bassham550, Maria Teresa Bassi1046, Robert C Bast Jr1273, Alakananda Basu1798,
\nMaria Teresa Batista1578, Henri Batoko1336, Maurizio Battino970, Kyle Bauckman2085, Bradley L Baumgarner1909,
\nK Ulrich Bayer1594, Rupert Beale1553, Jean-Fran¸cois Beaulieu1360, George R. Beck Jr48,294, Christoph Becker336,
\nJ David Beckham1595, Pierre-Andr e B edard749, Patrick J Bednarski301, Thomas J Begley1135, Christian Behl1419,
\nChristian Behrends757, Georg MN Behrens406, Kevin E Behrns1627, Eloy Bejarano26, Amine Belaid490,
\nFrancesca Belleudi1041, Giovanni B enard497, Guy Berchem706, Daniele Bergamaschi983, Matteo Bergami1401,
\nBen Berkhout1441, Laura Berliocchi714, Am elie Bernard1749, Monique Bernard1354, Francesca Bernassola1880,
\nAnne Bertolotti791, Amanda S Bess272, S ebastien Besteiro1351, Saverio Bettuzzi1828, Savita Bhalla913,
\nShalmoli Bhattacharyya973, Sujit K Bhutia838, Caroline Biagosch1159, Michele Wolfe Bianchi520,1378,1381,
\nMartine Biard-Piechaczyk210, Viktor Billes298, Claudia Bincoletto1314, Baris Bingol350, Sara W Bird1128, Marc Bitoun1112,
\nIvana Bjedov1258, Craig Blackstone843, Lionel Blanc1183, Guillermo A Blanco1496, Heidi Kiil Blomhoff1812,
\nEmilio Boada-Romero1297, Stefan B€ockler1464, Marianne Boes1423, Kathleen Boesze-Battaglia1835, Lawrence H Boise286,287,
\nAlessandra Bolino2063, Andrea Boman693, Paolo Bonaldo1823, Matteo Bordi897, J€urgen Bosch608, Luis M Botana1308,
\nJoelle Botti1375, German Bou1405, Marina Bouch e1038, Marion Bouchecareilh1331, Marie-Jos ee Boucher1901,
\nMichael E Boulton481, Sebastien G Bouret1926, Patricia Boya133, Micha€el Boyer-Guittaut1345, Peter V Bozhkov1141,
\nNathan Brady374, Vania MM Braga469, Claudio Brancolini1997, Gerhard H Braus353, Jos e M Bravo-San Pedro299,393,508,1374,
\nLisa A Brennan322, Emery H Bresnick2022, Patrick Brest490, Dave Bridges1939, Marie-Agn es Bringer124, Marisa Brini1822,
\nGlauber C Brito1311, Bertha Brodin631, Paul S Brookes1872, Eric J Brown352, Karen Brown1690, Hal E Broxmeyer480,
\nAlain Bruhat486,1339, Patricia Chakur Brum1893, John H Brumell446, Nicola Brunetti-Pierri315,1171,
\nRobert J Bryson-Richardson781, Shilpa Buch1777, Alastair M Buchan1819, Hikmet Budak1022, Dmitry V Bulavin118,505,1789,
\nScott J Bultman1792, Geert Bultynck665, Vladimir Bumbasirevic1470, Yan Burelle1356, Robert E Burke216,217,
\nMargit Burmeister1750, Peter B€utikofer1473, Laura Caberlotto1987, Ken Cadwell896, Monika Cahova112, Dongsheng Cai24,
\nJingjing Cai2099, Qian Cai1018, Sara Calatayud2007, Nadine Camougrand1343, Michelangelo Campanella1700,
\nGrant R Campbell1525, Matthew Campbell1249, Silvia Campello556,1876, Robin Candau1769, Isabella Caniggia1983,
\nLavinia Cantoni560, Lizhi Cao116, Allan B Caplan1656, Michele Caraglia1051, Claudio Cardinali1043, Sandra Morais Cardoso1579, Jennifer S Carew208, Laura A Carleton874, Cathleen R Carlin101, Silvia Carloni2002,
\nSven R Carlsson1267, Didac Carmona-Gutierrez1643, Leticia AM Carneiro312, Oliana Carnevali971, Serena Carra1318,
\nAlice Carrier120, Bernadette Carroll900, Caty Casas1324, Josefina Casas1116, Giuliana Cassinelli324, Perrine Castets1462,
\nSusana Castro-Obregon214, Gabriella Cavallini1841, Isabella Ceccherini568, Francesco Cecconi253,555,1884,
\nArthur I Cederbaum459, Valent ın Ce~na199,1281, Simone Cenci1323,2064, Claudia Cerella444, Davide Cervia1996,
\nSilvia Cetrullo1478, Hassan Chaachouay2028, Han-Jung Chae187, Andrei S Chagin634, Chee-Yin Chai626,628,
\nGopal Chakrabarti1502, Georgios Chamilos1601, Edmond YW Chan1142, Matthew TV Chan181, Dhyan Chandra1003,
\nPallavi Chandra548, Chih-Peng Chang818, Raymond Chuen-Chung Chang1653, Ta Yuan Chang345, John C Chatham1434,
\nSaurabh Chatterjee1910, Santosh Chauhan527, Yongsheng Che62, Michael E Cheetham1263, Rajkumar Cheluvappa1783,
\nChun-Jung Chen1153, Gang Chen598,1676, Guang-Chao Chen9, Guoqiang Chen1078, Hongzhuan Chen1077, Jeff W Chen1514,
\nJian-Kang Chen370,371, Min Chen249, Mingzhou Chen2104, Peiwen Chen1823, Qi Chen1674, Quan Chen172,
\nShang-Der Chen138, Si Chen325, Steve S-L Chen10, Wei Chen2125, Wei-Jung Chen829, Wen Qiang Chen979, Wenli Chen1113,
\nXiangmei Chen1133, Yau-Hung Chen1157, Ye-Guang Chen1250, Yin Chen1447, Yingyu Chen953,955, Yongshun Chen2135,
\nYu-Jen Chen712, Yue-Qin Chen1145, Yujie Chen1208, Zhen Chen339, Zhong Chen2123, Alan Cheng1702,
\nChristopher HK Cheng184, Hua Cheng1728, Heesun Cheong814, Sara Cherry1836, Jason Chesney1703,
\nChun Hei Antonio Cheung817, Eric Chevet1359, Hsiang Cheng Chi140, Sung-Gil Chi656, Fulvio Chiacchiera308,
\nHui-Ling Chiang958, Roberto Chiarelli1826, Mario Chiariello235,567,577, Marcello Chieppa835, Lih-Shen Chin290,
\nMario Chiong1285, Gigi NC Chiu878, Dong-Hyung Cho676, Ssang-Goo Cho650, William C Cho982, Yong-Yeon Cho105,
\nYoung-Seok Cho1064, Augustine MK Choi2095, Eui-Ju Choi656, Eun-Kyoung Choi387,400,685, Jayoung Choi1563,
\nMary E Choi2093, Seung-Il Choi2116, Tsui-Fen Chou412, Salem Chouaib395, Divaker Choubey1574, Vinay Choubey1936,
\nKuan-Chih Chow822, Kamal Chowdhury730, Charleen T Chu1856, Tsung-Hsien Chuang827, Taehoon Chun657,
\nHyewon Chung652, Taijoon Chung978, Yuen-Li Chung1194, Yong-Joon Chwae18, Valentina Cianfanelli254,
\nRoberto Ciarcia1775, Iwona A Ciechomska886, Maria Rosa Ciriolo1876, Mara Cirone1042, Sofie Claerhout1694,
\nMichael J Clague1698, Joan Cl aria1457, Peter GH Clarke1687, Robert Clarke361, Emilio Clementi1045,1398, C edric Cleyrat1781,
\nMiriam Cnop1366, Eliana M Coccia574, Tiziana Cocco1459, Patrice Codogno1375, J€orn Coers271, Ezra EW Cohen1533,
\nDavid Colecchia235,567,577, Luisa Coletto25, N uria S Coll123, Emma Colucci-Guyon516, Sergio Comincini1829,
\nMaria Condello578, Katherine L Cook2073, Graham H Coombs1929, Cynthia D Cooper2076, J Mark Cooper1395,
\nIsabelle Coppens601, Maria Tiziana Corasaniti1387, Marco Corazzari485,1884, Ramon Corbalan1566,
\nElisabeth Corcelle-Termeau251, Mario D Cordero1899, Cristina Corral-Ramos1289, Olga Corti507,1109, Andrea Cossarizza1767,
\nPaola Costelli1993, Safia Costes1518, Susan L Cotman721, Ana Coto-Montes946, Sandra Cottet566,1688, Eduardo Couve1301,
\nLori R Covey1015, L Ashley Cowart762, Jeffery S Cox1536, Fraser P Coxon1427, Carolyn B Coyne1846, Mark S Cragg1919,
\nRolf J Craven1679, Tiziana Crepaldi1995, Jose L Crespo1300, Alfredo Criollo1285, Valeria Crippa558, Maria Teresa Cruz1576,
\nAna Maria Cuervo26, Jose M Cuezva1277, Taixing Cui1907, Pedro R Cutillas987, Mark J Czaja27, Maria F Czyzyk-Krzeska1572,
\nRuben K Dagda2068, Uta Dahmen1404, Chunsun Dai800, Wenjie Dai1187, Yun Dai2059, Kevin N Dalby1940,
\nLuisa Dalla Valle1822, Guillaume Dalmasso1340, Marcello D’Amelio557, Markus Damme188, Arlette Darfeuille-Michaud1340,
\nCatherine Dargemont950, Victor M Darley-Usmar1433, Srinivasan Dasarathy205, Biplab Dasgupta202, Srikanta Dash1254,
\nCrispin R Dass242, Hazel Marie Davey8, Lester M Davids1560, David D avila227, Roger J Davis1731, Ted M Dawson604,
\nValina L Dawson606, Paula Daza1898, Jackie de Belleroche470, Paul de Figueiredo1180,1182,
\nRegina Celia Bressan Queiroz de Figueiredo135, Jos e de la Fuente1023, Luisa De Martino1775,
\nAntonella De Matteis1171, Guido RY De Meyer1443, Angelo De Milito631, Mauro De Santi2002,

This paper describes the concept of adaptive noise cancelling, an alternative method of estimating signals corrupted by additive noise or interference. The method uses a "primary" input containing the corrupted signal and a "reference" input containing noise correlated in some unknown way with the primary noise. The reference input is adaptively filtered and subtracted from the primary input to obtain the signal estimate. Adaptive filtering before subtraction allows the treatment of inputs that are deterministic or stochastic, stationary or time variable. Wiener solutions are developed to describe asymptotic adaptive performance and output signal-to-noise ratio for stationary stochastic inputs, including single and multiple reference inputs. These solutions show that when the reference input is free of signal and certain other conditions are met noise in the primary input can be essentiany eliminated without signal distortion. It is further shown that in treating periodic interference the adaptive noise canceller acts as a notch filter with narrow bandwidth, infinite null, and the capability of tracking the exact frequency of the interference; in this case the canceller behaves as a linear, time-invariant system, with the adaptive filter converging on a dynamic rather than a static solution. Experimental results are presented that illustrate the usefulness of the adaptive noise cancelling technique in a variety of practical applications. These applications include the cancelling of various forms of periodic interference in electrocardiography, the cancelling of periodic interference in speech signals, and the cancelling of broad-band interference in the side-lobes of an antenna array. In further experiments it is shown that a sine wave and Gaussian noise can be separated by using a reference input that is a delayed version of the primary input. Suggested applications include the elimination of tape hum or turntable rumble during the playback of recorded broad-band signals and the automatic detection of very-low-level periodic signals masked by broad-band noise.

Self-localized nonlinear excitations (solitons, polarons, and bipolarons) are fundamental and inherent features of quasi-one-dimensional conducting polymers. Their signatures are evident in many aspects of the physical and chemical properties of this growing class of novel materials. As a result, these polymers represent an opportunity for exploring the novel phenomena associated with topological solitons and their linear confinement which results from weakly lifting the ground-state degeneracy. The authors review the theoretical models that have been developed to describe the physics of polyacetylene and related conducting polymers and summarize the relevant experimental results obtained for these materials. An attempt is made to assess the validity of the soliton model of polyacetylene and its generalization to related systems in which the ground-state degeneracy has been lifted.

Abstract Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature 1 . Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium 2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses 3–15 , enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated—but distinct—DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.

1. To test the mode of functional connectivity in the basal ganglia circuitry, we studied the activity of simultaneously recorded neurons in the globus pallidus (GP) of a behaving rhesus monkey. The cross-correlograms of pairs of neurons in the GP were compared with those of neurons in the thalamus and frontal cortex and to the cross-correlograms of pallidal pairs after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. 2. In contrast with cortical and thalamic neuronal activity, almost all pairs (n = 76/81 pairs; 93.8%, 1,629/1,651 histograms; 98.7%) of GP neurons in the normal monkey were not driven by a common input. 3. The monkey was systemically treated with MPTP until the appearance of parkinsonian signs and an intermittent 7- to 11-Hz action/postural tremor. After the MPTP treatment, many pallidal neurons (49/140; 35%) became oscillatory, and 19% (n = 31/162) of pallidal pairs had oscillatory cross-correlograms. 4. These results support the model of parallel processing in the basal ganglia of normal monkeys and suggest a breakdown of the independent activity in the parkinsonian state.

We construct an index of firms' external finance constraints via generalized method of moments (GMM) estimation of an investment Euler equation. Unlike the commonly used KZ index, ours is consistent with firm characteristics associated with external finance constraints. Constrained firms' returns move together, suggesting the existence of a financial constraints factor. This factor earns a positive but insignificant average return. Much of the variation in this factor cannot be explained by the Fama--French and momentum factors. Cross-sectional regressions of returns on our index and other firm characteristics show that constrained firms earn higher returns and that the financial-constraints effect dominates the size effect. Copyright 2006, Oxford University Press.

Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment. The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity. The Cancer Genome Atlas consortium reports an integrative analysis of more than 400 samples of clear cell renal carcinoma on the basis of genomic, DNA methylation, RNA and proteomic characterization. The data reveal frequent mutations in the PI(3)K/AKT pathway, suggesting that this pathway might be a potential therapeutic target, in addition to an array of epigenetic alterations that are linked to specific mutations in chromatin-associated proteins. One notable finding is the presence of a metabolic shift in aggressive cancers, correlating with tumour stage and severity.

This paper presents a test of independence that can be applied to the estimated residuals of any time series model that can be transformed into a model driven by independent and identically distributed errors. The first order asymptotic distribution of the test statistic is independent of estimation error provided that the parameters of the model under test can be estimated -consistently. Because of this, our method can be used as a model selection tool and as a specification test. Widely used software1 written by Dechert and LeBaron can be used to implement the test. Also, this software is fast enough that the null distribution of our test statistic can be estimated with bootstrap methods. Our method can be viewed as a nonlinear analog of the Box-Pierce Q statistic used in ARIMA analysis.

Abstract Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale 1–3 . Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter 4 ; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation 5,6 ; analyses timings and patterns of tumour evolution 7 ; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity 8,9 ; and evaluates a range of more-specialized features of cancer genomes 8,10–18 .

From the Publisher: Fundamentals of Database Systems combines clear explanations of theory and design, broad coverage of models and real systems, and excellent examples with up-to-date introductions to modern database technologies. This edition is completely revised and updated, and reflects the latest trends in technological and application development. Professors Elmasri and Navathe focus on the relational model and include coverage of recent object-oriented developments. They also address advanced modeling and system enhancements in the areas of active databases, temporal and spatial databases, and multimedia information systems. This edition also surveys the latest application areas of data warehousing, data mining, web databases, digital libraries, GIS, and genome databases. New to the Third Edition Reorganized material on data modeling to clearly separate entity relationship modeling, extended entity relationship modeling, and object-oriented modeling Expanded coverage of the object-oriented and object/relational approach to data management, including ODMG and SQL3 Uses examples from real database systems including OracleTM and Microsoft AccessAE Includes discussion of decision support applications of data warehousing and data mining, as well as emerging technologies of web databases, multimedia, and mobile databases Covers advanced modeling in the areas of active, temporal, and spatial databases Provides coverage of issues of physical database tuning Discusses current database application areas of GIS, genome, and digital libraries

ABSTRACT We investigate the role of information in affecting a firm's cost of capital. We show that differences in the composition of information between public and private information affect the cost of capital, with investors demanding a higher return to hold stocks with greater private information. This higher return arises because informed investors are better able to shift their portfolio to incorporate new information, and uninformed investors are thus disadvantaged. In equilibrium, the quantity and quality of information affect asset prices. We show firms can influence their cost of capital by choosing features like accounting treatments, analyst coverage, and market microstructure.

This paper presents the findings of two studies that replicate previous work by Fred Davis on the subject of perceived usefulness, ease of use, and usage of information technology. The two studies focus on evaluating the psychometric properties of the ease of use and usefulness scales, while examining the relationship between ease of use, usefulness, and system usage. Study 1 provides a strong assessment of the convergent validity of the two scales by examining heterogeneous user groups dealing with heterogeneous implementations of messaging technology. In addition, because one might expect users to share similar perspectives about voice and electronic mail, the study also represents a strong test of discriminant validity. In this study a total of 118 respondents from 10 different organizations were surveyed for their attitudes toward two messaging technologies: voice and electronic mail. Study 2 complements the approach taken in Study 1 by focusing on the ability to demonstrate discriminant validity. Three popular software applications (WordPerfect, Lotus 1-2-3, and Harvard Graphics) were examined based on the expectation that they would all be rated highly on both scales. In this study a total of 73 users rated the three packages in terms of ease of use and usefulness. The results of the studies demonstrate reliable and valid scales for measurement of perceived ease of use and usefulness. In addition, the paper tests the relationships between ease of use, usefulness, and usage using structural equation modelling. The results of this model are consistent with previous research for Study 1, suggesting that usefulness is an important determinant of system use. For Study 2 the results are somewhat mixed, but indicate the importance of both ease of use and usefulness. Differences in conditions of usage are explored to explain these findings.

Single-wall fullerene nanotubes were converted from nearly endless, highly tangled ropes into short, open-ended pipes that behave as individual macromolecules. Raw nanotube material was purified in large batches, and the ropes were cut into 100- to 300-nanometer lengths. The resulting pieces formed a stable colloidal suspension in water with the help of surfactants. These suspensions permit a variety of manipulations, such as sorting by length, derivatization, and tethering to gold surfaces.

Abstract Models are presented for determining flow regime transitions in two‐phase gas‐liquid flow. The mechanisms for transition are based on physical concepts and are fully predictive in that no flow regime transitions are used in their development. A generalized flow regime map based on this theory is presented.