Detection of genetic aberrations in prenatal samples, obtained through amniocentesis or chorion villus biopsy, is increasingly performed using chromosomal microarray, a technique that can uncover both aneuploidies and copy number variants throughout the genome. Despite the obvious benefits of CMA, the decision on implementing the technology is complicated by ethical issues concerning variant interpretation and reporting. In Belgium, uniform guidelines were composed and a shared database for prenatal CMA findings was established. This Belgian approach sparks discussion: it is evidence-based, (...) prevents inconsistencies and avoids parental anxiety, but can be considered paternalistic. Here, we reflect on the cultural and moral bases of the Belgian reporting system of prenatally detected variants. (shrink)

Advances in biochemistry, chemistry and engineering have enabled the development of a new gene expression assay. This ‘chip‐based’ approach utilizes microscopic arrays of cDNAs printed on glass as high‐density hybridization targets. Fluorescent probe mixtures derived from total cellular messenger RNA (mRNA) hybridize to cognate elements on the array, allowing accurate measurement of the expression of the corresponding genes. Array densities of >1,000 cDNAs per cm2 enable quantitative expression monitoring of a large number of genes in a single hybridization. A two‐color (...) fluorescence detection scheme allows rapid and simultaneous differential expression analysis of independent biological samples. Mass‐produced microarrays provide a new tool for genome expression analysis that may revolutionize genetic dissection, drug discovery and human disease diagnostics. (shrink)

DNA microarrays are perfectly suited for comparing gene expression in different populations of cells. An important application of microarray techniques is identifying genes which are activated by a particular drug of interest. This process will allow biologists to identify therapies targeted to particular diseases, and, eventually, to gain more knowledge about the biological processes in organisms. Such an application is described in this paper. It is focused on diabetes and obesity, which is a genetically heterogeneous disease, meaning that multiple (...) defective genes are responsible for the diseases. The paper is divided in three parts, each dealing with a different problem addressed to our study. First we validate the data from our microarray experiment. We identified significant systematic sources of variability which are potentially issues for other microarray datasets. Second, we applied multiple hypothesis testing to identify differentially expressed genes. We found a set of genes which appear to change in expression level over time in response to a drug treatment. Third, we tried to address the problem of identification of co-expressed genes using cluster analysis. This last problem is still under discussion. (shrink)

We argue that the most‐promising area of clinical application of microarrays in the foreseeable future is the diagnostics and monitoring of infectious diseases. Microarrays for the detection and characterization of human pathogens have already found their way into clinical practice in some countries. After discussing the persistent, yet often underestimated, importance of infectious diseases for public health, we consider the technologies that are best suited for the detection and clinical investigation of pathogens. Clinical application of microarray technologies for the (...) detection of mycobacteria, Bacillus anthracis, HIV, hepatitis and influenza viruses, and other major pathogens, as well as the analysis of their drug‐resistance patterns, illustrate our main thesis. BioEssays 30:673–682, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

We present evidence of a potentially serious source of error intrinsic to all spotted cDNA microarrays that use IMAGE clones of expressed sequence tags (ESTs). We found that a high proportion of these EST sequences contain 5V-end poly(dT) sequences that are remnants from the oligo(dT)-primed reverse transcription of polyadenylated mRNA templates used to generate EST cDNA for sequence clone libraries. Analysis of expression data from two single-dye cDNA microarray experiments showed that ESTs whose sequences contain repeats of consecutive (...) 5V- end dT residues appeared to be strongly coexpressed, while expression data of all other sequences exhibited no such pattern. Our analysis suggests that expression data from sequences containing 5V poly(dT) tracts are more likely to be due to systematic cross-hybridization of these poly(dT) tracts than to true mRNA coexpression. This indicates that existing data generated by cDNA microarrays containing IMAGE clone ESTs should be filtered to remove expression data containing significant 5V poly(dT) tracts. D 2003 Elsevier Inc. All rights reserved. (shrink)

The Affymetrix GeneChip is a popular microarray platform for genome‐wide expression profiling and has been widely used in functional genomics especially in the classification of cancers. Due to the updating of genome data, much of the genome information with which the chips were designed is out‐of‐date and it has been reported that many of the genes/transcripts on the chips differ from their original definition when mapping the probes to the new genome information. Dai et al. have reported that the (...) updated definition can cause as much as 30–50% discrepancy in the genes selected as differentially expressed on a heart tissue expression profiling dataset. Understanding the nature of this difference is therefore very important for the utilization of the data. In this work, with a large cancer dataset as an example, we compared two major definitions and investigated their effects on classification, clustering, discovery of differentially expressed genes and gene‐set‐based analysis. Results show that the two definitions agree well on clustering and classification results but genes and gene sets discovered as differentially expressed or enriched can be very different. Discoveries based on the Affymetrix definition can cover most of those based on the new definition, but tend to have more false positives. BioEssays 28: 739–746, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

We present evidence of a potentially serious source of error intrinsic to all spotted cDNA microarrays that use IMAGE clones of expressed sequence tags (ESTs). We found that a high proportion of these EST sequences contain 5V-end poly(dT) sequences that are remnants from the oligo(dT)-primed reverse transcription of polyadenylated mRNA templates used to generate EST cDNA for sequence clone libraries. Analysis of expression data from two single-dye cDNA microarray experiments showed that ESTs whose sequences contain repeats of consecutive (...) 5V- end dT residues appeared to be strongly coexpressed, while expression data of all other sequences exhibited no such pattern. Our analysis suggests that expression data from sequences containing 5V poly(dT) tracts are more likely to be due to systematic cross-hybridization of these poly(dT) tracts than to true mRNA coexpression. This indicates that existing data generated by cDNA microarrays containing IMAGE clone ESTs should be filtered to remove expression data containing significant 5V poly(dT) tracts. D 2003 Elsevier Inc. All rights reserved. (shrink)

This paper addresses the issue of the stability of lists of genes identified as differentially expressed in microarray experiments. The similarities be- tween gene rankings yielded by various gene selection methods performed with resampled datasets were assessed. The mean percentage of overlapping genes for two rankings varied from 10 to 90% depending on the applied gene selection method and the size of the list. The assessment of the stability of obtained gene rankings seems to be relevant in the (...) class='Hi'>analysis of microarray data. (shrink)

In this post‐sequencing era, geneticists can focus on functional genomics on a much larger scale than ever before. One goal is the discovery and elucidation of the intricate genetic networks that co‐ordinate transcriptional activation in different regulatory circuitries. High‐throughput gene expression measurement using DNA arrays has thus become routine strategy. This approach, however, does not directly identify gene loci that belong to the same regulatory group; e.g., those that are bound by a common (set of) transcription factor(s). Working in yeast, (...) two groups have recently published an elegant method that could circumvent this problem, by combining chromatin immunoprecipitation and DNA microarrays.(1,2) The method is likely to provide a powerful tool for the dissection of global regulatory networks in eukaryotic cells. BioEssays 23:473–476, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

In this paper we will offer a few examples to illustrate the orientation of contemporary research in data analysis and we will investigate the corresponding role of mathematics. We argue that the modus operandi of data analysis is implicitly based on the belief that if we have collected enough and sufficiently diverse data, we will be able to answer most relevant questions concerning the phenomenon itself. This is a methodological paradigm strongly related, but not limited to, biology, and (...) we label it the microarray paradigm. In this new framework, mathematics provides powerful techniques and general ideas which generate new computational tools. But it is missing any explicit isomorphism between a mathematical structure and the phenomenon under consideration. This methodology used in data analysis suggests the possibility of forecasting and analyzing without a structured and general understanding. This is the perspective we propose to call agnostic science, and we argue that, rather than diminishing or flattening the role of mathematics in science, the lack of isomorphisms with phenomena liberates mathematics, paradoxically making more likely the practical use of some of its most sophisticated ideas. (shrink)

Statistics play a critical role in biological and clinical research. However, most reports of scientific results in the published literature make it difficult for the reader to reproduce the statistical analyses performed in achieving those results because they provide inadequate documentation of the statistical tests and algorithms applied. The Ontology of Biological and Clinical Statistics (OBCS) is put forward here as a step towards solving this problem. Terms in OBCS, including ‘data collection’, ‘data transformation in statistics’, ‘data visualization’, ‘statistical data (...) analysis’, and ‘drawing a conclusion based on data’, cover the major types of statistical processes used in basic biological research and clinical outcome studies. OBCS is aligned with the Basic Formal Ontology (BFO) and extends the Ontology of Biomedical Investigations (OBI), an OBO (Open Biological and Biomedical Ontologies) Foundry ontology supported by over 20 research communities. We discuss two examples illustrating how the ontology is being applied. In the first (biological) use case, we describe how OBCS was applied to represent the high throughput microarray data analysis of immunological transcriptional profiles in human subjects vaccinated with an influenza vaccine. In the second (clinical outcomes) use case, we applied OBCS to represent the processing of electronic health care data to determine the associations between hospital staffing levels and patient mortality. Our case studies were designed to show how OBCS can be used for the consistent representation of statistical analysis pipelines under two different research paradigms. By representing statistics-related terms and their relations in a rigorous fashion, OBCS facilitates standard data analysis and integration, and supports reproducible biological and clinical research. (shrink)

The use of genomic testing in pregnancy is increasing, giving rise to questions over how the information that is generated should be offered and returned in clinical practice. While these tests provide important information for prenatal decision-making, they can also generate information of uncertain significance. This paper critically examines three models for approaching the disclosure of variants of uncertain significance (VUS), which can arise from forms of genomic testing such as prenatal chromosomal microarray analysis (CMA). Contrary to prevailing (...) arguments, we argue that respect for reproductive autonomy does not justify adopting a model on which an offer to disclose VUS is a routine part of genetic counselling. Instead, we contend that a commitment both to solidarity between healthcare providers and pregnant women and to the acceptance of a novel principle of caution under normative uncertainty means that we should instead adopt a model of VUS disclosure that imposes a strong presumption against offering to disclose VUS. The upshot of this is that it should be standard practice to only offer to disclose VUS when this is requested by the woman undergoing CMA. We defend our position against claims that arise from an alleged right to such information and that a presumption against an offer will lead to inequity. (shrink)

The vast majority (> 95%) of single-gene mutations in yeast affect not only the expression of the mutant gene, but also the expression of many other genes. These data suggest the presence of a previously uncharacterized ‘gene expression network’—a set of interactions between genes which dictate gene expression in the native cell environment. Here, we quantitatively analyze the gene expression network revealed by microarray expression data from 273 different yeast gene deletion mutants.(1) We find that gene expression interactions form (...) a robust, error-tolerant ‘scale-free’ network, similar to metabolic pathways(2) and artificial networks such as power grids and the internet.(3-5) Because the connectivity between genes in the gene expression network is unevenly distributed, a scale-free organization helps make organisms resistant to the deleterious effects of mutation, and is thus highly adaptive. The existence of a gene expression network poses practical considerations for the study of gene function, since most mutant phenotypes are the result of changes in the expression of many genes. Using principles of scale-free network topology, we propose that fragmenting the gene expression network via ‘genome-engineering’ may be a viable and practical approach to isolating gene function. BioEssays 24:267–274, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10054. (shrink)

CtBP family proteins predominantly function as transcriptional corepressors. Studies with mutant mouse suggest that the two mouse genes, Ctbp1 and Ctbp2, play unique and redundant gene regulatory roles during development.1 Ctbp1-deficient mice are viable, but are small and die early, while Ctbp2 deficiency leads to embryonic lethality. Ctbp2-null mutation causes defects in axial patterning, heart morphogenesis and neural development. The Ctbp2 mutant phenotype is more severe in the absence of Ctbp1. The studies with Ctbp2 mutant embryos suggest that CtBP can (...) also activate transcription. A plant CtBP homolog, Angustifolia (AN), has recently been identified.2, 3 AN controls polar elongation of leaf cells via the microtubule cytoskeleton. Microarray analysis suggests that AN also functions as a transcriptional repressor. Thus, the CtBP family proteins control cellular processes by serving as transcriptional activators and regulators of the cytoskeleton as well as transcriptional corepressors. BioEssays 25:9–12, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

Increasingly, genomic analysis is being utilized to diagnose children with developmental delay or dysmorphic facial features suggestive of a congenital disorder. Genetic testing has rapidly evolved, and the genome-wide tests that we use today are significantly different from the more targeted single-gene tests of the last decade. Chromosomal microarray analysis is now a first line test for children with multiple birth defects, children with intellectual impairment, and children with an unusual constellation of symptoms that do not fit (...) with a known disease. There are three types of CMA that are currently clinically available. CMA by oligonucleotide array-based comparative genomic hybridization compares the hybridization signal from the patient's DNA to that of a reference DNA sample for each oligonucleotide on the array. Depending on the specific array, this can range from tens of thousands to hundreds of thousands of oligonucleotides. (shrink)

Increasingly, genomic analysis is being utilized to diagnose children with developmental delay or dysmorphic facial features suggestive of a congenital disorder. Genetic testing has rapidly evolved, and the genome-wide tests that we use today are significantly different from the more targeted single-gene tests of the last decade. Chromosomal microarray analysis is now a first line test for children with multiple birth defects, children with intellectual impairment, and children with an unusual constellation of symptoms that do not fit (...) with a known disease. There are three types of CMA that are currently clinically available. CMA by oligonucleotide array-based comparative genomic hybridization compares the hybridization signal from the patient's DNA to that of a reference DNA sample for each oligonucleotide on the array. Depending on the specific array, this can range from tens of thousands to hundreds of thousands of oligonucleotides. (shrink)

Reactive oxygen species (ROS) are known as toxic metabolic products in plants and other aerobic organisms. An elaborate and highly redundant plant ROS network, composed of antioxidant enzymes, antioxidants and ROS-producing enzymes, is responsible for maintaining ROS levels under tight control. This allows ROS to serve as signaling molecules that coordinate an astonishing range of diverse plant processes. The specificity of the biological response to ROS depends on the chemical identity of ROS, intensity of the signal, sites of production, plant (...) developmental stage, previous stresses encountered and interactions with other signaling molecules such as nitric oxide, lipid messengers and plant hormones. Although many components of the ROS signaling network have recently been identified, the challenge remains to understand how ROS-derived signals are integrated to eventually regulate such biological processes as plant growth, development, stress adaptation and programmed cell death. (shrink)

Gene clustering is a useful exploratory technique to group together genes with similar expression levels under distinct cell cycle phases or distinct conditions. It helps the biologist to identify potentially meaningful relationships between genes. In this study, we propose a clustering method based on multivariate normal mixture models, where the number of clusters is predicted via sequential hypothesis tests: at each step, the method considers a mixture model of m components (m = 2 in the first step) and tests if (...) in fact it should be m - 1. If the hypothesis is rejected, m is increased and a new test is carried out. The method continues (increasing m) until the hypothesis is accepted. The theoretical core of the method is the full Bayesian significance test, an intuitive Bayesian approach, which needs no model complexity penalization nor positive probabilities for sharp hypotheses. Numerical experiments were based on a cDNA microarray dataset consisting of expression levels of 205 genes belonging to four functional categories, for 10 distinct strains of Saccharomyces cerevisiae. To analyze the method’s sensitivity to data dimension, we performed principal components analysis on the original dataset and predicted the number of classes using 2 to 10 principal components. Compared to Mclust (model-based clustering), our method shows more consistent results. (shrink)

Technology has outpaced the capacity of researchers performing research on human participants to interpret all data generated and handle those data responsibly. This poses a critical challenge to existing rules governing human subjects research. The technologies used in research to generate images, scans, and data can now produce so much information that there is significant potential for incidental findings, findings generated in the course of research but beyond the aims of the study. Neuroimaging scans may visualize the entire brain and (...) even the entire head; computed tomography colonography research may visualize the entire torso, from the base of the lungs to the pubis; genetics studies may reveal “extra” and sometimes unwanted information about the family, such as misattributed paternity and undisclosed adoption; and genomic microarray research increasingly involves whole-genome analysis revealing an individual’s complete genotype, with enormous potential for uncovering unexpected information about an individual’s genetics and risks of developing future conditions. (shrink)

Matrices that cannot be handled using conventional clustering, regression or classification methods are often found in every big data research area. In particular, datasets with thousands or millions of rows and less than a hundred columns regularly appear in biological so-called omic problems. The effectiveness of conventional data analysis approaches is hampered by this matrix structure, which necessitates some means of reduction. An evolutionary method called PreCLAS is presented in this article. Its main objective is to find a submatrix (...) with fewer rows that exhibits some group structure. Three stages of experiments were performed. First, a benchmark dataset was used to assess the correct functionality of the method for clustering purposes. Then, a microarray gene expression data matrix was used to analyze the method’s performance in a simple classification scenario, where differential expression was carried out. Finally, several classification methods were compared in terms of classification accuracy using an RNA-seq gene expression dataset. Experiments showed that the new evolutionary technique significantly reduces the number of rows in the matrix and intelligently performs unsupervised row selection, improving classification and clustering methods. (shrink)

During the last few months, several pioneer genome‐wide transcriptomic, proteomic and metabolomic studies have revolutionised the understanding of bacterial biological processes, leading to a picture that resembles eukaryotic complexity. Technological advances such as next‐generation high‐throughput sequencing and high‐density oligonucleotide microarrays have allowed the determination, in several bacteria, of the entire boundaries of all expressed transcripts. Consequently, novel RNA‐mediated regulatory mechanisms have been discovered including multifunctional RNAs. Moreover, resolution of bacterial proteome organisation (interactome) and global protein localisation (localizome) have unveiled an (...) unanticipated complexity that highlights the significance of protein multifunctionality and localisation in the cell. Also, analysis of a complete bacterial metabolic network has again revealed a high fraction of multifunctional enzymes and an unexpectedly high level of metabolic responses and adaptation. Altogether, these novel approaches have permitted the deciphering of the entire physiological landscape of one of the smallest bacteria, Mycoplasma pneumoniae. Here, we summarise and discuss recent findings aimed at defining the blueprint of any prokaryote. (shrink)

The generation of patterns and the diversity of cell types in a multicellular organism require differential gene regulation. At the heart of this process are enhancers or cis‐regulatory modules (CRMs), genomic regions that are bound by transcription factors (TFs) that control spatio‐temporal gene expression in developmental networks. To date, only a few CRMs have been studied in detail and the underlying cis‐regulatory code is not well understood. Here, we review recent progress on the genome‐wide identification of CRMs with chromatin immunoprecipitation (...) of TF‐DNA complexes followed by microarrays (ChIP‐on‐chip). We focus on two computational approaches that have succeeded in predicting the expression pattern driven by a CRM either based on TF binding site preferences and their expression levels, or quantitative analysis of CRM occupancy by key TFs. We also discuss the current limits of these methods and highlight some of the key problems that have to be solved to gain a more complete understanding of the structure and function of CRMs. (shrink)

Although DNA microarrays are now widely used in research settings, they have been slow to penetrate clinical practice in spite of their apparent advantages. This is due to the very different requirements for a clinical test in contrast to a research tool, and to a strict necessity for demonstrated clinical utility. There is a clear differentiation between two types of DNA array tests: “genomic” diagnostics, developed to ascertain the presence or absence of mutations, deletions or duplications, and for which clinical (...) evidence is already established, and tests using expression profiling for prognosis or predictive purposes, in which case the clinical correlate must be proven. Most array diagnostics currently used belong, understandably, to the “genomic” variety. It is to be expected that future improvements in tailored technology, as well as a logical trend towards measuring an ever‐increasing number of parameters, will ensure an important diagnostic role for DNA arrays in the coming decade. BioEssays 29:699–705, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

An unabridged edition with updated footnotes and layout, to include: Recent Criticisms of "Consciousness" - Instinct and Habit - Desire and Feeling - Influence of Past History on Present Occurrences in Living Organisms - Psychological and Physical Causal Laws - Introspection - The Definition of Perception - Sensations and Images - Memory - Words and Meaning - General Ideas and Thought - Belief - Truth and Falsehood - Emotions and Will - Characteristics of Mental Phenomena.

Despite their success in describing and predicting cognitive behavior, the plausibility of so-called ‘rational explanations’ is often contested on the grounds of computational intractability. Several cognitive scientists have argued that such intractability is an orthogonal pseudoproblem, however, since rational explanations account for the ‘why’ of cognition but are agnostic about the ‘how’. Their central premise is that humans do not actually perform the rational calculations posited by their models, but only act as if they do. Whether or not the problem (...) of intractability is solved by recourse to ‘as if’ explanations critically depends, inter alia, on the semantics of the ‘as if’ connective. We examine the five most sensible explications in the literature, and conclude that none of them circumvents the problem. As a result, rational ‘as if’ explanations must obey the minimal computational constraint of tractability. (shrink)

This anthology is a thorough introduction to classic literature for those who have not yet experienced these literary masterworks. For those who have known and loved these works in the past, this is an invitation to reunite with old friends in a fresh new format. From Shakespeare's finesse to Oscar Wilde's wit, this unique collection brings together works as diverse and influential as The Pilgrim's Progress and Othello. As an anthology that invites readers to immerse themselves in the masterpieces of (...) the literary giants, it is must-have addition to any library. (shrink)

In his highly regarded history of the rise of clinical trials in America, HarryMarks describes how their widespread adoption resulted largely fromthe efforts of ‘therapeutic reformers’ who sought to replace the individualexpertise of clinicians with the ‘science of controlled experiment’. Thetransition described by Marks resembles in many respects the transition fromthe ‘truth-to-nature’ objectivity of individual experts to a ‘mechanical’ formof objectivity portrayed by Daston and Galison. In particular,Marks details the passage from a regime of trust in expertise and experts to (...) aregime based on the mechanical generation of data, the elimination ofhuman judgement and the adoption of a ‘view from nowhere’ where individual and group idiosyncrasies are systematically suppressedthrough recourse to quantitative methods.[...]. (shrink)

In his highly regarded history of the rise of clinical trials in America, HarryMarks describes how their widespread adoption resulted largely fromthe efforts of ‘therapeutic reformers’ who sought to replace the individualexpertise of clinicians with the ‘science of controlled experiment’. Thetransition described by Marks resembles in many respects the transition fromthe ‘truth-to-nature’ objectivity of individual experts to a ‘mechanical’ formof objectivity portrayed by Daston and Galison. In particular,Marks details the passage from a regime of trust in expertise and experts to (...) aregime based on the mechanical generation of data, the elimination ofhuman judgement and the adoption of a ‘view from nowhere’ where individual and group idiosyncrasies are systematically suppressedthrough recourse to quantitative methods.[...]. (shrink)

This book was completed by the early 1960s and published in 1984 but it has not lost its topicality, for it contains an important re-assessment of the relations of two main streams of contemporary philosophy - the Analytical and the Dialectic. Adherents and critics of these traditions tend to assurnethat they are diametrically opposed, that their roots, concerns and approaches contradict each other, and that no reconciliation is possible. In contradistinction Russell derives both traditions from the common root of the (...) dissatisfaction with the arguments against speculative philosophy. These according to the author leave a lacuna - certain elementsof our Weltanschaaung have been removed, but they cannot be removed without replacement lest we have an incomplete world view, so incomplete in fact that it cannot be viable. According to Russell part of this vacuum is taken up by the analytical tradition but this tradition is not capable of taking up the remainder of it. That portion of the vacant space is however taken up by the dialectical tradi tion, which in turn cannot itself handle the whole of the problem. Thus the two reactions to the demise of speculative philosophy appear to be complementary in at least this sense. But the author goes further, for according to hirn the analytical arguments themselves clearly point to the emergence of dialectical problems, and the dialectical problems themselves need some such background to arise. (shrink)

As one of the tools used to express feelings and thoughts, music has been utilised by people in many fields throughout history. Music is seen as a means of expressing religious feelings, being used as an educational tool, as a way for military bands to invoke heroic feelings in soldiers, and as way of expressing emotions in joyful and melancholic days. Music was especially born and shaped by rituals of religious origin. With the spread of the religion of Islam, music (...) became an issue that paved the way for many religious discussions. It should be clearly noted that while many verses in the Qur'an are cited as a source for these discussions, it is very difficult to deduce from these verses whether music is halal (permissible) or haram (prohibited). Additionally, many permissible matters in Islam become prohibited when used maliciously or out of their intended purpose, however, if everything that has a possibility of being used maliciously or outside of its intended purpose is considered haram, this will lead to a path of denying many blessings that Allah has bestowed upon people in this world. Restricting issues out of the possibility of their wrongful misuse and depriving others of this blessings cannot be just. Nevertheless, although the discussion of music as permissible or prohibited has largely existed within the religion of Islam, those involved with Tasawwuf (Islamic Mysticism), also known as Sufis, have generally perceived music as nutrient for the soul. Consequently, Sufis have incorporated music into their worship in order to invoke religious feelings over the centuries. Religious music is divided into two; the first is Mosque Recitations, and the second is Tekke music (also known as Tasawwuf Music). Mosque Recitation is that which is performed without instrumentals using only vocals and an improvised approach. On the other hand, Tekke music is performed with an instrument and a composed written piece. Within the Mosque Recitation is the Qur’an recitation, which when read in accordance with its rules has a natural phonetic style, meaning that when the Qur’an is recited according to the Maqam (Melodic modes of recitation) requirements, it evokes spiritual feelings to the listeners. Accordingly, there is a connection between the recitation of the Qur'an and the scientific understanding of music. When a connection between the Qur’an and disciplined recitation is established, this causes an artistic sensation to the listener, which experts in the field have name “Fem-i Muhsin”. Hafız (a title used for a person who has memorised the Qur’an in its entirety) Bekir Sıdkı Sezgin is one of the important musicians to have left his mark on Turkish music, where a discipline was formed after him. He has a very high status due to the value he gave to Turkish music as he became one of the leading names in Turkish music, especially considering the large yet unknown number of students that he personally trained. Hafız Bekir states in interviews that he especially owed his success in the science of music to the Qur'an education he received at a young age, and he emphasises that those who are on the way to becoming good musicians must receive a Qur'an education; additionally, because classical Turkish music lyrics are Arabic and Persian, he argues that the way to correctly pronounce these lyrics is to also know Ottoman Turkish to a high degree. Hafız Bekir was also able to recite the Qur'an to a degree of perfection and was proud of being a Hafız, where he believed that the Qur'an harmonised between his memory and excellent musical knowledge. Hafız Bekir recited the Qur’an according to the suitable Istanbul Maqam of reading, and by using the Maqam befitting the Qur’an recitation, Hafız Bekir was able to take the listeners on a spiritual journey. A survey of the works produced about Hafız Bekir shows that although there have been many theses, articles, and interviews published about him, there is no specific study on his Qur’an recitation according to the Istanbul Maqam style. In this study, Hafız Bekir’s dual identity as both a musician and Qur’an Hafız is underlined as a way to contribute to the field by revealing this side of Hafız Bekir, and also examining the Qur'an education that he recommends to his students. The recitation of verses 189-194 of the chapter Âli İmrân, which Hafız Bekir recited in the Istanbul Maqam style, is notated with the Mus notation system, and analysed according to the Maqam reading style. The notation is formed based on a sensory evaluation with assistance from experts in the field. This study, as a musical analysis, was produced to reveal the importance of this subject to interested parties. (shrink)

This fundamental and straightforward text addresses a weakness observed among present-day students, namely a lack of familiarity with formal proof. Beginning with the idea of mathematical proof and the need for it, associated technical and logical skills are developed with care and then brought to bear on the core material of analysis in such a lucid presentation that the development reads naturally and in a straightforward progression. Retaining the core text, the second edition has additional worked examples which users (...) have indicated a need for, in addition to more emphasis on how analysis can be used to tell the accuracy of the approximations to the quantities of interest which arise in analytical limits. (shrink)

This title presents a comprehensive guide to interpretative phenomenological analysis (IPA) which is an increasingly popular approach to qualitative inquiry taught to undergraduate and postgraduate students today.

With the development of teachers’ psychological cognition, the moral education curriculum develops as per the changes in times. Currently, a resurgence of interest on studying teachers’ perceptions of the moral education curriculum has observed. This is because moral education curriculum of each country plays a unique role in the overall design of the country’s education curriculum. However, studies on teachers’ perceptions of the moral education curriculum are scarce, and no framework has been developed to guide the teaching and learning of (...) teachers for the moral education curriculum for schools. The moral education curriculum serves as one of the main vehicles for value education, with teachers as direct executors. It can influence the overall development of the school system and long-term development of a country. Thus, in this paper, we reviewed current literature related to teachers’ perceptions of the moral education curriculum and developed future trends considering teachers’ perceptions of the moral education curriculum in improving existing moral education programs in a country. We identified a list of keywords related to moral education curriculum and teacher perceptions and relevant to the scope of this study. These keywords were used to search the articles from the Scopus and WoS studies. Overall, 32 papers meeting the search criteria were retrieved. Further, we conducted thematic studies, and four themes were successfully identified: the model of teacher perceptions of moral and national education, the dimensions of the teacher ethics model, teaching strategies, and the role of teachers. The results of this study suggested a new framework for research trends in teachers’ perception models, particularly toward the moral education curriculum. This study contributed to the knowledge regarding teaching and learning approaches of moral education considering teachers’ perceptions of the moral education curriculum. The findings of study would benefit future studies and would improve the implementation of a country’s moral education program. (shrink)

How do our embodied experiences of music shape our analysis, theorizing, and interpretation of musical texts, and our engagement with practices including composing, improvising, listening, and performing? 'Music, Analysis, and the Body: Experiments, Explorations, and Embodiments' is a pioneering essay collection uniting major and emerging scholars to consider how theory and analysis address music's literal and figurative bodies. The essayists offer critical overviews of different theoretical approaches to music analysis and embodiment, then test and demonstrate their (...) ideas in specific repertoires. The range of musics analysed is diverse: Western art music sits alongside non-Western repertoires, folk songs, jazz, sound art, audio-visual improvisations, soundtracks, sing-alongs, live events, popular songs, and the musical analysis of non-musical experiences. Topics examined include affect, agency, energetics, feel, gesture, metaphor, mimesis, rehearsal, subjectivity, and the objects of music analysis--as well as acoustic ecology, alterity, class, distraction, excess, political authority, sensoriality, technology, and transcendence. (shrink)

Throughout this text, many of the research paradigms and methodologies across experimental analysis of behavior (EAB) and applied behavior analysis (ABA) are presented within the "bench-to-bedside" approach of translational research described by the National Institutes of Health. The first few chapters of the text introduce underlying core tenets of behaviorism as well as core characteristics and methods that define the field of behavior analysis. The next several chapters of the book introduce the reader to some of the (...) foundational principles of behavior analysis, with coverage from both the EAB and ABA perspectives. The final chapters of the book cover topics for which there has been ample basic, applied, and translational research conducted. The text concludes with a chapter on ethics, which includes content related to ethical issues in research, ethical issues in clinical practice, and the ethical use of nonhuman animals and special populations in research. (shrink)

Of the many proposals for inferring genetic regulatory structure from microarray measurements of mRNA transcript hybridization, several aim to estimate regulatory structure from the associations of gene expression levels measured in repeated samples. The repeated samples may be from a single experimental condition, or from several distinct experimental conditions; they may be “equilibrium” measurements or time series; the associations may be estimated by correlation coefficients or by conditional frequencies (for discretized measurements) or by some other statistic. This paper describes (...) two elementary statistical difficulties for all such procedures, no matter whether based on Bayesian updating, conditional independence testing, or other machine learning procedures such as simulated annealing or neural net pruning. One difficulty obtains if large numbers of cells are aggregated in a measurement of expression levels from a common population of cells; the other obtains if small numbers of cells are aggregated or if samples are separately aggregated over different populations of cells. (shrink)

A part of European cultural patrimony rests on the relationships our ancestors had with time. A few examples chosen at random will suffice to show how their attitude toward this point evolved over the ages. The famous Carpe Diem by Horace was an invitation to take advantage of the present moment. In Jewish tradition man‘s obligation to work was considered a curse. Similarly a saying attributed by Pliny to the painter Appelles emphasized the necessity of daily labor. In still other (...) ages time appeared as the great destroyer of all things, and Christianity promised its enemies tortures that were no less eternal than the joys it reserved for its disciples. (shrink)

Is conceptual analysis required for reductive explanation? If there is no a priori entailment from microphysical truths to phenomenal truths, does reductive explanation of the phenomenal fail? We say yes . Ned Block and Robert Stalnaker say no.

While the idea of philosophy as conceptual analysis has attracted many adherents and undergone a number of variations, in general it suffers from an authority problem with two dimensions. First, it is unclear why the analysis of a concept should have objective authority: why explicating what we mean should express how things are. Second, conceptual analysis seems to lack intersubjective authority: why philosophical analysis should apply to more than a parochial group of individuals. I argue that (...) Hegel’s conception of social ontology, focused on his concept of “ethical life” (Sittlichkeit), helps to explain how concepts (and their explication) have both objective and intersubjective authority in the social domain. Hegel claims that modern institutions are the product of self-conscious purposes, so that they are conceptually constituted. Concepts do not just represent these objects and so depend on a contingent relation to them. As many contemporary social ontologists agree, this means that our concepts of these institutions are uniquely epistemically “transparent.” They have objective authority. Concepts have intersubjective authority in the modern world as well, according to Hegel. However, I show that this feature of Hegel’s account does not rely on the solution to a philosophical problem. Rather, since the concepts of modern ethical life are “essentially contested,” their content depends on the practical and political agreement of modern subjects. This means that concepts can only have objective authority if some prior intersubjective agreement has been reached. The role of philosophy as conceptual analysis is thus importantly dependent on political developments. (shrink)

Die Gegenwartsgesellschaft bewertet die Infragestellung des inhaltlichen Gehaltes von Glaubensüberzeugungen als Tugend. Auch innerhalb der Theologie gewinnt der Zweifel zunehmend an Relevanz, wird aber überwiegend immer noch als Gefährdung des Glaubens wahrgenommen. Deshalb unterzieht die Autorin den Akt des Zweifelns einer philosophischtheologischen Analyse. In Auseinandersetzung mit entsprechenden Positionen - z. B. Augustinus, Thomas von Aquin, Hegel oder Kierkegaard - geht sie dem vermeintlichen Widerspruch zwischen Glauben und Zweifeln auf den Grund und zeigt die theologische Legitimität iterativen Zweifelns auf.

Of the many proposals for inferring genetic regulatory structure from microarray measurements of mRNA transcript hybridization, several aim to estimate regulatory structure from the associations of gene expression levels measured in repeated samples. The repeated samples may be from a single experimental condition, or from several distinct experimental conditions; they may be “equilibrium” measurements or time series; the associations may be estimated by correlation coefficients or by conditional frequencies (for discretized measurements) or by some other statistic. This paper describes (...) two elementary statistical difficulties for all such procedures, no matter whether based on Bayesian updating, conditional independence testing, or other machine learning procedures such as simulated annealing or neural net pruning. One difficulty obtains if large numbers of cells are aggregated in a measurement of expression levels from a common population of cells; the other obtains if small numbers of cells are aggregated or if samples are separately aggregated over different populations of cells. (shrink)

Consists in part of papers developed at the Sixth International Whitehead Conference, held in the summer of 2006 at the Universit'at Salzburg, Austria.

Rigorous formal proof is one of the key techniques in the natural sciences, engineering, and of course also in the formal sciences. Progress in automated reasoning increasingly enables computer systems to support, and even teach, users to conduct formal a.