Multiplicity Of Hypotheses Research Articles

An integrative gene network-based approach to uncover the cellular and molecular infrastructures of schizophrenia

AimsHigh phenotypic and endophenotypic heritability of schizophrenia indicates substantial involvement of genetic elements in the occurrence of this disorder. Multiplicity of hypotheses about the genetic basis of schizophrenia pathogenesis suggests that there is still no integrated image from cellular and molecular infrastructure of this disorder. Materials and methodsHere, we aimed to gain an integrated insight into the genetic basis of schizophrenia through gene set enrichment and network analysis to find the most important developmental stages/brain regions, chromosomal locations and metabolic pathways involved in the pathogenesis of schizophrenia. We investigated major mental disorders whose genetic bases are significantly overlapping with the schizophrenia gene set. Key findingsEnrichment analyses uncovered 60 developmental stages/brain regions, 21 chromosomal hotspots and 16 pathways which are significantly associated with the found gene set. Our results demonstrated early mid-fetal/cortex as the most prominent developmental stage/brain region, chr16q22 as the most significant cytoband and the neuroactive ligand-receptor interaction as the most central pathway associated with schizophrenia. Further analyses revealed that autistic disorder has the most shared genes with schizophrenia. Moreover, mitogen-activated protein kinase-3 (MAPK3), calcium voltage-gated channel subunit alpha1 C (CACNA1C), solute carrier family 6 member 4 (SLC6A4) and 5-hydroxytryptamine receptor 2A (HTR2A) genes are the most central genes in the pathogenesis of schizophrenia. SignificanceIn addition to summarizing what has been found on schizophrenia-associated genes in an integrative holistic framework, our results may help identify principle schizophrenia-associated cellular and molecular infrastructures, and provide support for further investigation on potential diagnostic and therapeutic biomarkers for schizophrenia.

The relative effects of dimensionality and multiplicity of hypotheses on the $F$-test in linear regression

Recently, several authors have re-examined the power of the classical F-test in linear regression in a `large-p, large-n' framework (cf. Zhong and Chen (2011), Wang and Cui (2013)). They highlight the loss of power as the number of regressors p increases relative to sample size n. These papers essentially focus only on the overall test of the null hypothesis that all p slope coefficients are equal to zero. Here, we consider the general case of testing q linear hypotheses on the (p+1)-dimensional regression parameter vector that includes p slope coefficients and an intercept parameter. In the case of Gaussian design, we describe the dependence of the local asymptotic power function on both the relative number of parameters p and the number of hypotheses q being tested, showing that the negative effect of dimensionality is less severe if the number of hypotheses is small. Using the recent work of Srivastava and Vershynin (2013) on high dimensional sample covariance matrices we are also able to substantially generalize previous results for non-Gaussian regressors.

Approaches to multiplicity issues in complex research in microarray analysis

The multiplicity problem is evident in the simplest form of statistical analysis of gene expression data – the identification of differentially expressed genes. In more complex analysis, the problem is compounded by the multiplicity of hypotheses per gene. Thus, in some cases, it may be necessary to consider testing millions of hypotheses. We present three general approaches for addressing multiplicity in large research problems. (a) Use the scalability of false discovery rate (FDR) controlling procedures; (b) apply FDR‐controlling procedures to a selected subset of hypotheses; (c) apply hierarchical FDR‐controlling procedures. We also offer a general framework for ensuring reproducible results in complex research, where a researcher faces more than just one large research problem. We demonstrate these approaches by analyzing the results of a complex experiment involving the study of gene expression levels in different brain regions across multiple mouse strains.

NEW DIRECTIONS IN AMERICAN URBAN HISTORY

Howard Gillette Jr. and Zane L. Miller, eds. American Urbanism: A Historiographical Review. New York: Greenwood Press, 1987. vi + 328 pp. Patricia Mooney Melvin. The Organic City: Urban Definition and Community Organization, 1880-1920. Lexington: University Press of Kentucky, 1987. xii + 227 pp. Philip Abbott. Seeking Many Inventions: The Idea of Community in America. Knoxville: University of Tennessee Press, 1987. x + 214 pp. As a distinct field of inquiry, American urban history is now reaching a point at which many contributors are pausing to reflect on what has been accomplished in the field and on what new directions need to be established. As Howard Gillette Jr. points out in his introduction to our first selection in this review, "Central to the timing of this book is the transitional nature of urban history as a distinctive field of study"(l). And yet, from the time of its dramatic growth in the 1960s, American urban historiography has always been in a state of transition. Innovative methodologies and theories are still being advanced by those on the forefront of pioneering efforts. But despite the multiplicity of hypotheses, directions and conclusions which were pursued in the 1970s, most urban historians felt increasingly secure about the legitimacy of their collective endeavour as the decade progressed. The birth in 1974 of the Journal of Urban History, the numerous serial publications in urban studies launched by academic presses, and the advent of a variety of university programs in the field all seemed to be more than hopeful signs. Urban historians were already consolidating their positions and gathering into rival schools of thought. Back in 1971, when Stephan Thernstrom boldly challenged the very legitimacy of urban studies, his voice stood out as one of lonely dissent. But now, it appears, the academic consolidation which urban history achieved in the 1970s is facing formidable criticism from several fronts. Notable practitioners such as Theodore Hershberg of the once- thriving Philadelphia History Project, or Sam Bass Warner Jr., who formerly was dedicated to the reformist potential of urban history, have reached bleak conclusions concerning the survival of their respective approaches. Stephan Thernstrom's critique is no longer quite so isolated. But this new collection of fourteen essays has not been compiled to examine a sub-discipline entering a period of crisis or decline; instead, these articles serve to identify, through their retrospective examinations of past work, new methodological and ideological directions for American urban historiography. The authors' respective messages strike an optimistic chord. Their advocacy of new interpretative approaches seeks to build on past accomplishments rather than to abandon failed efforts.

Simple Dielectric Liquids

T J Gallagher London: Clarendon/Oxford University Press 1975 pp vi + 154 price £6 The study of electrical conduction and breakdown in hydrocarbon and cryogenic liquids has resulted in an extensive and often conflicting body of experimental evidence, augmented by a multiplicity of hypotheses nearly all of which lack satisfactory authentication. Very recent experimental advances have, however, yielded results of such significance as to demand a thorough reappraisal of the whole topic.