From holism to compositionality: memes and the evolution of segmentation, syntax, and signification in music and language

Steven Mithen argues that language evolved from an antecedent he terms “Hmmmmm, [meaning it was] Holistic, manipulative, multi-modal, musical and mimetic”. Owing to certain innate and learned factors, a capacity for segmentation and cross-stream mapping in early Homo sapiens broke the continuous line of Hmmmmm, creating discrete replicated units which, with the initial support of Hmmmmm, eventually became the semantically freighted words of modern language. That which remained after what was a bifurcation of Hmmmmm arguably survived as music, existing as a sound stream segmented into discrete units, although one without the explicit and relatively fixed semantic content of language. All three types of utterance – the parent Hmmmmm, language, and music – are amenable to a memetic interpretation which applies Universal Darwinism to what are understood as language and musical memes. On the basis of Peter Carruthers’ distinction between ‘cognitivism’ and ‘communicativism’ in language, and William Calvin’s theories of cortical information encoding, a framework is hypothesized for the semantic and syntactic associations between, on the one hand, the sonic patterns of language memes (‘lexemes’) and of musical memes (‘musemes’) and, on the other hand, ‘mentalese’ conceptual structures, in Chomsky’s ‘Logical Form’ (LF)

Combined flow cytometry and high-throughput image analysis for the study of essential genes in Caenorhabditis elegans

Background: Advances in automated image-based microscopy platforms coupled with high-throughput liquid workflows have facilitated the design of large-scale screens utilising multicellular model organisms such as Caenorhabditis elegans to identify genetic interactions, therapeutic drugs or disease modifiers. However, the analysis of essential genes has lagged behind because lethal or sterile mutations pose a bottleneck for high-throughput approaches, and a systematic way to analyse genetic interactions of essential genes in multicellular organisms has been lacking. Results: In C. elegans, non-conditional lethal mutations can be maintained in heterozygosity using chromosome balancers, commonly expressing green fluorescent protein (GFP) in the pharynx. However, gene expression or function is typically monitored by the use of fluorescent reporters marked with the same fluorophore, presenting a challenge to sort worm populations of interest, particularly at early larval stages. Here, we develop a sorting strategy capable of selecting homozygous mutants carrying a GFP stress reporter from GFP-balanced animals at the second larval stage. Because sorting is not completely error-free, we develop an automated high-throughput image analysis protocol that identifies and discards animals carrying the chromosome balancer. We demonstrate the experimental usefulness of combining sorting of homozygous lethal mutants and automated image analysis in a functional genomic RNA interference (RNAi) screen for genes that genetically interact with mitochondrial prohibitin (PHB). Lack of PHB results in embryonic lethality, while homozygous PHB deletion mutants develop into sterile adults due to maternal contribution and strongly induce the mitochondrial unfolded protein response (UPR mt ). In a chromosome-wide RNAi screen for C. elegans genes having human orthologues, we uncover both known and new PHB genetic interactors affecting the UPR mt and growth. Conclusions: The method presented here allows the study of balanced lethal mutations in a high-throughput manner. It can be easily adapted depending on the user's requirements and should serve as a useful resource for the C. elegans community for probing new biological aspects of essential nematode genes as well as the generation of more comprehensive genetic networks.European Research Council ERC-2011-StG-281691Ministerio de Economía y Competitividad BFU2012–3550

The structure and evolution of breast cancer genomes

Chromosome changes in the haematological malignancies, lymphomas and sarcomas are known to be important events in the evolution of these tumours as they can, for example, form fusion oncogenes or disrupt tumour suppressor genes. The recently described recurrent fusion genes in prostate and lung cancer proved to be iconic examples as they indicated that important gene fusions are found in the common epithelial cancers also. Breast cancers often display extensive structural and numerical chromosome aberration and have among the most complex karyotyes of all cancers. Genome rearrangements are potentially an important source of mutation in breast cancer but little is known about how they might contribute to this disease. My first aim was to carry out a structural survey of breast cancer cell line genomes in order to find genes that were disrupted by chromosome aberrations in “typical” breast cancers. I investigated three breast cancer cell lines, HCC1187, VP229 and VP267 using data from array painting, SNP6 array CGH, molecular cytogenetics and massively parallel paired end sequencing. I then used these structural genomic maps to predict fusion transcripts and demonstrated expression of five fusion transcripts in HCC1187, three in VP229 and four in VP267. Even though chromosome aberrations disrupt and fuse many genes in individual breast cancers, a major unknown is the relative importance and timing of genome rearrangements compared to sequence-level mutation. For example, chromosome instability might arise early and be essential to tumour suppressor loss and fusion gene formation or be a late event contributing little to cancer development. To address this question, I considered the evolution of these highly rearranged breast cancer karyotypes. The VP229 and VP267 cell lines were derived from the same patient before and after therapy-resistant relapse, so any chromosome aberration found in both cell lines was probably found in the common in vivo ancestor of the two cell lines. A large majority of structural variants detected by massively parallel paired end sequencing, including three fusion transcripts, were found in both cell lines, and therefore, in the common ancestor. This probably means that the bulk of genome rearrangement pre-dated the relapse. For HCC1187, I classified most of its mutations as earlier or later according to whether they occurred before or after a landmark event in the evolution of the genome - endoreduplication (duplication of its entire genome). Genome rearrangements and sequence-level mutations were fairly evenly divided between earlier and later, implying that genetic instability was relatively constant throughout the evolution of the tumour. Surprisingly, the great majority of inactivating mutations and expressed gene fusions happened earlier. The non-random timing of these events suggests many were selected.This work was supported by the Medical Research Council Studentshi

Performance Modelling and Optimisation of Multi-hop Networks

A major challenge in the design of large-scale networks is to predict and optimise the total time and energy consumption required to deliver a packet from a source node to a destination node. Examples of such complex networks include wireless ad hoc and sensor networks which need to deal with the effects of node mobility, routing inaccuracies, higher packet loss rates, limited or time-varying effective bandwidth, energy constraints, and the computational limitations of the nodes. They also include more reliable communication environments, such as wired networks, that are susceptible to random failures, security threats and malicious behaviours which compromise their quality of service (QoS) guarantees. In such networks, packets traverse a number of hops that cannot be determined in advance and encounter non-homogeneous network conditions that have been largely ignored in the literature. This thesis examines analytical properties of packet travel in large networks and investigates the implications of some packet coding techniques on both QoS and resource utilisation. Specifically, we use a mixed jump and diffusion model to represent packet traversal through large networks. The model accounts for network non-homogeneity regarding routing and the loss rate that a packet experiences as it passes successive segments of a source to destination route. A mixed analytical-numerical method is developed to compute the average packet travel time and the energy it consumes. The model is able to capture the effects of increased loss rate in areas remote from the source and destination, variable rate of advancement towards destination over the route, as well as of defending against malicious packets within a certain distance from the destination. We then consider sending multiple coded packets that follow independent paths to the destination node so as to mitigate the effects of losses and routing inaccuracies. We study a homogeneous medium and obtain the time-dependent properties of the packet’s travel process, allowing us to compare the merits and limitations of coding, both in terms of delivery times and energy efficiency. Finally, we propose models that can assist in the analysis and optimisation of the performance of inter-flow network coding (NC). We analyse two queueing models for a router that carries out NC, in addition to its standard packet routing function. The approach is extended to the study of multiple hops, which leads to an optimisation problem that characterises the optimal time that packets should be held back in a router, waiting for coding opportunities to arise, so that the total packet end-to-end delay is minimised

Probabilistic structural mechanics research for parallel processing computers

Aerospace structures and spacecraft are a complex assemblage of structural components that are subjected to a variety of complex, cyclic, and transient loading conditions. Significant modeling uncertainties are present in these structures, in addition to the inherent randomness of material properties and loads. To properly account for these uncertainties in evaluating and assessing the reliability of these components and structures, probabilistic structural mechanics (PSM) procedures must be used. Much research has focused on basic theory development and the development of approximate analytic solution methods in random vibrations and structural reliability. Practical application of PSM methods was hampered by their computationally intense nature. Solution of PSM problems requires repeated analyses of structures that are often large, and exhibit nonlinear and/or dynamic response behavior. These methods are all inherently parallel and ideally suited to implementation on parallel processing computers. New hardware architectures and innovative control software and solution methodologies are needed to make solution of large scale PSM problems practical

Low Power Processor Architectures and Contemporary Techniques for Power Optimization – A Review

The technological evolution has increased the number of transistors for a given die area significantly and increased the switching speed from few MHz to GHz range. Such inversely proportional decline in size and boost in performance consequently demands shrinking of supply voltage and effective power dissipation in chips with millions of transistors. This has triggered substantial amount of research in power reduction techniques into almost every aspect of the chip and particularly the processor cores contained in the chip. This paper presents an overview of techniques for achieving the power efficiency mainly at the processor core level but also visits related domains such as buses and memories. There are various processor parameters and features such as supply voltage, clock frequency, cache and pipelining which can be optimized to reduce the power consumption of the processor. This paper discusses various ways in which these parameters can be optimized. Also, emerging power efficient processor architectures are overviewed and research activities are discussed which should help reader identify how these factors in a processor contribute to power consumption. Some of these concepts have been already established whereas others are still active research areas. © 2009 ACADEMY PUBLISHER

Multiscale, multimodal analysis of tumor heterogeneity in IDH1 mutant vs wild-type diffuse gliomas.

Glioma is recognized to be a highly heterogeneous CNS malignancy, whose diverse cellular composition and cellular interactions have not been well characterized. To gain new clinical- and biological-insights into the genetically-bifurcated IDH1 mutant (mt) vs wildtype (wt) forms of glioma, we integrated data from protein, genomic and MR imaging from 20 treatment-naïve glioma cases and 16 recurrent GBM cases. Multiplexed immunofluorescence (MxIF) was used to generate single cell data for 43 protein markers representing all cancer hallmarks, Genomic sequencing (exome and RNA (normal and tumor) and magnetic resonance imaging (MRI) quantitative features (protocols were T1-post, FLAIR and ADC) from whole tumor, peritumoral edema and enhancing core vs equivalent normal region were also collected from patients. Based on MxIF analysis, 85,767 cells (glioma cases) and 56,304 cells (GBM cases) were used to generate cell-level data for 24 biomarkers. K-means clustering was used to generate 7 distinct groups of cells with divergent biomarker profiles and deconvolution was used to assign RNA data into three classes. Spatial and molecular heterogeneity metrics were generated for the cell data. All features were compared between IDH mt and IDHwt patients and were finally combined to provide a holistic/integrated comparison. Protein expression by hallmark was generally lower in the IDHmt vs wt patients. Molecular and spatial heterogeneity scores for angiogenesis and cell invasion also differed between IDHmt and wt gliomas irrespective of prior treatment and tumor grade; these differences also persisted in the MR imaging features of peritumoral edema and contrast enhancement volumes. A coherent picture of enhanced angiogenesis in IDHwt tumors was derived from multiple platforms (genomic, proteomic and imaging) and scales from individual proteins to cell clusters and heterogeneity, as well as bulk tumor RNA and imaging features. Longer overall survival for IDH1mt glioma patients may reflect mutation-driven alterations in cellular, molecular, and spatial heterogeneity which manifest in discernable radiological manifestations

A Comprehensive Survey of Deep Learning in Remote Sensing: Theories, Tools and Challenges for the Community

In recent years, deep learning (DL), a re-branding of neural networks (NNs), has risen to the top in numerous areas, namely computer vision (CV), speech recognition, natural language processing, etc. Whereas remote sensing (RS) possesses a number of unique challenges, primarily related to sensors and applications, inevitably RS draws from many of the same theories as CV; e.g., statistics, fusion, and machine learning, to name a few. This means that the RS community should be aware of, if not at the leading edge of, of advancements like DL. Herein, we provide the most comprehensive survey of state-of-the-art RS DL research. We also review recent new developments in the DL field that can be used in DL for RS. Namely, we focus on theories, tools and challenges for the RS community. Specifically, we focus on unsolved challenges and opportunities as it relates to (i) inadequate data sets, (ii) human-understandable solutions for modelling physical phenomena, (iii) Big Data, (iv) non-traditional heterogeneous data sources, (v) DL architectures and learning algorithms for spectral, spatial and temporal data, (vi) transfer learning, (vii) an improved theoretical understanding of DL systems, (viii) high barriers to entry, and (ix) training and optimizing the DL.Comment: 64 pages, 411 references. To appear in Journal of Applied Remote Sensin

Body mereology

The body is made up of parts. This basic assumption is central in most neuroscientific studies of bodily sensation, body representation and motor action. Yet, the assumption has rarely been considered explicitly. We may indeed ask how the body is internally segmented and how body parts can be defined. That is, how can we sketch the mereology of the body? Here we distinguish between a somatosensory mereology and a motor mereology

Measurements, Models, Systems and Design

531 s.