G-spots cause incorrect expression measurement in Affymetrix microarrays

Abstract Background High Density Oligonucleotide arrays (HDONAs), such as the Affymetrix HG-U133A GeneChip, use sets of probes chosen to match specified genes, with the expectation that if a particular gene is highly expressed then all the probes in that gene's probe set will provide a consistent message signifying the gene's presence. However, probes that contain a G-spot (a sequence of four or more guanines) behave abnormally and it has been suggested that these probes are responding to some biochemical effect such as the formation of G-quadruplexes. Results We have tested this expectation by examining the correlation coefficients between pairs of probes using the data on thousands of arrays that are available in the NCBI Gene Expression Omnibus (GEO) repository. We confirm the finding that G-spot probes are poorly correlated with others in their probesets and reveal that, by contrast, they are highly correlated with one another. We demonstrate that the correlation is most marked when the G-spot is at the 5' end of the probe. Conclusion Since these G-spot probes generally show little correlation with the other members of their probesets they are not fit for purpose and their values should be excluded when calculating gene expression values. This has serious implications, since more than 40% of the probesets in the HG-U133A GeneChip contain at least one such probe. Future array designs should avoid these untrustworthy probes. </jats:sec

Affymetrix probes containing runs of contiguous guanines are not gene-specific

High Density Oligonucleotide arrays (HDONAs), such as the Affymetrix HG-U133A GeneChip, use sets of probes chosen to match specified genes, with the expectation that if a particular gene is highly expressed then all the probes in the designated probe set will provide a consistent message signifying the gene&#x27;s presence. However, we demonstrate by data mining thousands of CEL files from NCBI&#x27;s GEO database that 4G-probes (defined as probes containing sequences of four or more consecutive guanine (G) bases) do not react in the intended way. Rather, possibly due to the formation of G-quadruplexes, most 4G-probes are correlated, irrespective of the expression of the thousands of genes for which they were separately intended. It follows that 4G-probes should be ignored when calculating gene expression levels. Furthermore, future microarray designs should make no use of 4G-probes

A Comparative Study of the Impact of G-Stack Probes on Various Affymetrix GeneChips of Mammalia

We have previously discovered that probes containing runs of four or more contiguous guanines are not reliable for measuring gene expression in the Human HG_U133A Affymetrix GeneChip data. These probes are not correlated with other members of their probe set, but they are correlated with each other. We now extend our analysis to different3′GeneChip designs of mouse, rat, and human. We find that, in all these chip designs, the G-stack probes (probes with a run of exactly four consecutive guanines) are correlated highly with each other, indicating that such probes are not reliable measures of gene expression in mammalian studies. Furthermore, there is no specific position of G-stack where the correlation is highest in all the chips. We also find that the latest designs of rat and mouse chips have significantly fewer G-stack probes compared to their predecessors, whereas there has not been a similar reduction in G-stack density across the changes in human chips. Moreover, we find significant changes in RMA values (after removing G-stack probes) as the number of G-stack probes increases.</jats:p

The English School of Chess: A Nation on Display, 1834-1904

Chess, the first truly universal sport, experienced unique national tensions, as the regularity of international master chess and the presence of foreign professionals in England brought matters of nationality into sharp focus. In continuing the historian’s search for English national identity, this thesis will explore the growth of nineteenth-century chess to examine the implications of these national tensions. It will concentrate on the growth and conceptualization of international master chess, as well as the wider growth of the professional and amateur game. It will consist of four chapters, and will cover an 80-year period, starting in 1834, the year of the first contest between England and France, and ending in 1904, the creation of British Chess Federation. The overarching means for projecting national sentiments onto the game was through the construction of the English School of Chess. During the period, it was both a representative body of English ability on the international stage, as well as a national spirit of play; an international competitor as well as a distinct national school of thought. The two distinct aspects to its construction allowed contemporaries to use it as both a symbol of national superiority, and a platform for the imagining of an “English” way of playing the game. The former tied in with the conceptualising of international master chess, as writers and players constructed it as a tester of national prestige, while the latter tied into the wider anxieties surrounding the respectability of play that defined the period. The latter followed the same lines as the construction of an amateur ethos in other sports, but was framed and envisaged, against the image of the foreign professional, as innately “English”. Its meaning changed over time, as contemporaries imagined the two aspects to its conception with contrasting significance across the period. The one constant factor was the underlying desire to use its meaning to imagine England as a special, distinct, and superior nation

A computational dynamical model of human visual cortex for visual search and feature-based attention

Visual attention can be deployed to locations within the visual array (spatial attention), to individual features such as colour and form (feature-based attention), or to entire objects (object-based attention). Objects are composed of features to form a perceived ‘whole’. This compositional object representation reduces the storage demands by avoiding the need to store every type of object experienced. However, this approach exposes a problem of binding these constituent features (e.g. form and colour) into objects. The problem is made explicit in the higher areas of the ventral stream as information about a feature’s location is absent. For feature-based attention and search, activations flow from the inferotemporal cortex to primary visual cortex without spatial cues from the dorsal stream, therefore the neural effect is applied to all locations across the visual field [79, 60, 7, 52]. My research hypothesis is that biased competition occurs independently for each cued feature, and is implemented by lateral inhibition between a feedforward and a feedback network through a cortical micro-circuit architecture. The local competition for each feature can be combined in the dorsal stream via spatial congruence to implement a secondary spatial attention mechanism, and in early visual areas to bind together the distributed featural representation of a target object

COMPLEX TRAINING: AN EVALUATION OF POTENTIATION BETWEEN A 3RM BACK SQUAT AND A SQUAT JUMP

Complex training (CT) is increasingly popular among strength and conditioning coaches. CT hypothesises that a near maximal muscle contraction will enhance the explosive capabilities of the muscle given the exercises are biomechanically similar (Docherty et al., 2004). Previous CT research has focused on intra-complex potentiation between near maximum exercises and a similar stretch-shortening cycle exercise. The effect of CT on starting strength (SS) has yet to be explored. The optimal rest interval between the loaded exercise and the explosive exercise is somewhat unclear. Comyns et al. (2006) investigated potentiation between a 5RM back squat (BS) and a counter movement jump. Results varied between individuals. The purpose of this study was to determine if a heavy loaded exercise (3RM BS) results in a performance increase on a SS exercise (squat jump)

Can Social Categorisation Elicit Own-Group Biases in Face Recognition

Previous research has demonstrated a number of own-group biases in face recognition. For example, people are better at recognising own-race compared to other-race faces (Meissner & Brigham, 2001); and own-age compared to other-age faces (Anastasi & Rhodes, 2012). However, exactly why these own-group biases occur is unclear. Perceptual expertise and social-cognitive accounts have been put forward in an attempt to explain these effects. The first suggests the own-group advantage arises from the relatively increased experience (and therefore expertise) we have differentiating own-group faces; while the second suggests these effects are simply the result of categorising a face as belonging to our ‘in’ or ‘out’ group. Two studies explored whether own-group biases can be brought about by mere categorisation at encoding. Participants were shown 40 facial images grouped according to in-/out-group status. Study One used University membership as the grouping variable; while Study Two grouped faces (and participants) according to their position on Brexit (i.e. as Leave or Remain supporters). Differences in accuracy for in- and out-group faces were investigated, alongside the influence of in-group affiliation strength. Results are discussed in terms of the perceptual expertise and social-cognitive explanations of own-group biases

Gender and authority in British women hymn-writers' use of metre, 1760-1900

This article is part of a cluster that draws material from the recent conference Metre Matters: New Approaches to Prosody, 1780–1914. It comprises an introduction by Jason David Hall and six articles presented at the conference, whose aim was to address renewed scholarly interest in versification and form across the long nineteenth century, as well as some of the methodologies underpinning it. The papers included in the cluster look both to the minutiae of Romantic and Victorian metres and to their cultural intertexts. The conference, hosted by the University of Exeter's Centre for Victorian Studies, was held 3–5 July 2008

AN INVESTIGATION OF SCHEMA THEORY APPLIED TO THE BIOMECHANICS OF THE SPRINT START IN ATHLETICS

Schmidt’s schema theory (1975) predicts that variable practice (VP) will outperform constant practice (CP). The implications of this for the teaching of skills such as the sprint start are that VP should allow equal or better learning to CP. The aim of this study was to examine the effect on novice subjects of practicing with varying block settings on the learning of the sprint start. A deterministic model of the spint start was derived using the guidelines of Hay and Reid (1982) to identify factor likely to affect performance. Measures of the factors were obtained using video and laser analysis. The affect of VP and CP on these factors was evaluated using a pre, post retention expermental design. Performance of the sprint start was compared between VP (n=6), CP (n=5), and Control (n=5) groups. Results showed no significant difference (

AN INVESTIGATION OF SCHEMA THEORY APPLIED TO THE BIOMECHANICS OF THE SPRINT START IN ATHLETICS

Schmidt’s schema theory (1975) predicts that variable practice (VP) will outperform constant practice (CP). The implications of this for the teaching of skills such as the sprint start are that VP should allow equal or better learning to CP. The aim of this study was to examine the effect on novice subjects of practicing with varying block settings on the learning of the sprint start. A deterministic model of the spint start was derived using the guidelines of Hay and Reid (1982) to identify factor likely to affect performance. Measures of the factors were obtained using video and laser analysis. The affect of VP and CP on these factors was evaluated using a pre, post retention expermental design. Performance of the sprint start was compared between VP (n=6), CP (n=5), and Control (n=5) groups. Results showed no significant difference (