Supervised Aggregative Feature Extraction for Big Data Time Series Regression

In many applications, and especially those where batch processes are involved, a target scalar output of interest is often dependent on one or more time series of data. With the exponential growth in data logging in modern industries such time series are increasingly available for statistical modeling in soft sensing applications. In order to exploit time series data for predictive modelling, it is necessary to summarise the information they contain as a set of features to use as model regressors. Typically this is done in an unsupervised fashion using simple techniques such as computing statistical moments, principal components or wavelet decompositions, often leading to significant information loss and hence suboptimal predictive models. In this paper, a functional learning paradigm is exploited in a supervised fashion to derive continuous, smooth estimates of time series data (yielding aggregated local information), while simultaneously estimating a continuous shape function yielding optimal predictions. The proposed Supervised Aggregative Feature Extraction (SAFE) methodology can be extended to support nonlinear predictive models by embedding the functional learning framework in a Reproducing Kernel Hilbert Spaces setting. SAFE has a number of attractive features including closed form solution and the ability to explicitly incorporate first and second order derivative information. Using simulation studies and a practical semiconductor manufacturing case study we highlight the strengths of the new methodology with respect to standard unsupervised feature extraction approaches.

LD Score regression distinguishes confounding from polygenicity in genome-wide association studies

Both polygenicity (many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from a true polygenic signal and bias. We have developed an approach, LD Score regression, that quantifies the contribution of each by examining the relationship between test statistics and linkage disequilibrium (LD). The LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control. We find strong evidence that polygenicity accounts for the majority of the inflation in test statistics in many GWAS of large sample size.

Of no fixed form: The Irish Pavilion at Venice 2014 and beyond

This paper explores the theme of exhibiting architectural research through a particular example, the development of the Irish pavilion for the 14th architectural biennale, Venice 2014. Responding to Rem Koolhaas’s call to investigate the international absorption of modernity, the Irish pavilion became a research project that engaged with the development of the architectures of infrastructure in Ireland in the twentieth and twenty-first centuries. Central to this proposition was that infrastructure is simultaneously a technological and cultural construct, one that for Ireland occupied a critical position in the building of a new, independent post-colonial nation state, after 1921.

Presupposing infrastructure as consisting of both visible and invisible networks, the idea of a matrix become a central conceptual and visual tool in the curatorial and design process for the exhibition and pavilion. To begin with this was a two-dimensional grid used to identify and order what became described as a series of ten ‘infrastructural episodes’. These were determined chronologically across the decades between 1914 and 2014 and their spatial manifestations articulated in terms of scale: micro, meso and macro. At this point ten academics were approached as researchers. Their purpose was twofold, to establish the broader narratives around which the infrastructures developed and to scrutinise relevant archives for compelling visual material. Defining the meso scale as that of the building, the media unearthed was further filtered and edited according to a range of categories – filmic/image, territory, building detail, and model – which sought to communicate the relationship between the pieces of architecture and the larger systems to which they connect. New drawings realised by the design team further iterated these relationships, filling in gaps in the narrative by providing composite, strategic or detailed drawings.

Conceived as an open-ended and extendable matrix, the pavilion was influenced by a series of academic writings, curatorial practices, artworks and other installations including: Frederick Kiesler’s City of Space (1925), Eduardo Persico and Marcello Nizzoli’s Medaglio d’Oro room (1934), Sol Le Witt’s Incomplete Open Cubes (1974) and Rosalind Krauss’s seminal text ‘Grids’ (1979). A modular frame whose structural bays would each hold and present an ‘episode’, the pavilion became both a visual analogue of the unseen networks embodying infrastructural systems and a reflection on the predominance of framed structures within the buildings exhibited. Sharing the aspiration of adaptability of many of these schemes, its white-painted timber components are connected by easily-dismantled steel fixings. These and its modularity allow the structure to be both taken down and re-erected subsequently in different iterations. The pavilion itself is, therefore, imagined as essentially provisional and – as with infrastructure – as having no fixed form. Presenting archives and other material over time, the transparent nature of the space allowed these to overlap visually conveying the nested nature of infrastructural production. Pursuing a means to evoke the qualities of infrastructural space while conveying a historical narrative, the exhibition’s termination in the present is designed to provoke in the visitor, a perceptual extension of the matrix to engage with the future.

High Performance Real-time Pre-Processing for Fixed-Complexity Sphere Decoder

Pre-processing (PP) of received symbol vector and channel matrices is an essential pre-requisite operation for Sphere Decoder (SD)-based detection of Multiple-Input Multiple-Output (MIMO) wireless systems. PP is a highly complex operation, but relative to the total SD workload it represents a relatively small fraction of the overall computational cost of detecting an OFDM MIMO frame in standards such as 802.11n. Despite this, real-time PP architectures are highly inefficient, dominating the resource cost of real-time SD architectures. This paper resolves this issue. By reorganising the ordering and QR decomposition sub operations of PP, we describe a Field Programmable Gate Array (FPGA)-based PP architecture for the Fixed Complexity Sphere Decoder (FSD) applied to 4 × 4 802.11n MIMO which reduces resource cost by 50% as compared to state-of-the-art solutions whilst maintaining real-time performance.

Natural Killer Cell-like signature observed in locally advanced rectal cancer after neoadjuvant chemoradiotherapy in a tumour regression grade dependent manner

Background: Around 10-15% of patients with locally advanced rectal cancer (LARC) undergo a pathologically complete response (TRG4) to neoadjuvant chemoradiotherapy; the rest of patients exhibit a spectrum of tumour regression (TRG1-3). Understanding therapy-related genomic alterations may help us to identify underlying biology or novel targets associated with response that could increase the efficacy of therapy in patients that do not benefit from the current standard of care.
Methods: 48 FFPE rectal cancer biopsies and matched resections were analysed using the WG-DASL HumanHT-12_v4 Beadchip array on the illumina iScan. Bioinformatic analysis was conducted in Partek genomics suite and R studio. Limma and glmnet packages were used to identify genes differentially expressed between tumour regression grades. Validation of microarray results will be carried out using IHC, RNAscope and RT-PCR.
Results: Immune response genes were observed from supervised analysis of the biopsies which may have predictive value. Differential gene expression from the resections as well as pre and post therapy analysis revealed induction of genes in a tumour regression dependent manner. Pathway mapping and Gene Ontology analysis of these genes suggested antigen processing and natural killer mediated cytotoxicity respectively. The natural killer-like gene signature was switched off in non-responders and on in the responders. IHC has confirmed the presence of Natural killer cells through CD56+ staining.
Conclusion: Identification of NK cell genes and CD56+ cells in patients responding to neoadjuvant chemoradiotherapy warrants further investigation into their association with tumour regression grade in LARC. NK cells are known to lyse malignant cells and determining whether their presence is a cause or consequence of response is crucial. Interrogation of the cytokines upregulated in our NK-like signature will help guide future in vitro models.

HDAC1 and HDAC2 independently predict mortality in hepatocellular carcinoma by a competing risk regression model in a Southeast Asian population

Histone deacetylases (HDACs) are enzymes involved in transcriptional repression. We aimed to examine the significance of HDAC1 and HDAC2 gene expression in the prediction of recurrence and survival in 156 patients with hepatocellular carcinoma (HCC) among a South East Asian population who underwent curative surgical resection in Singapore. We found that HDAC1 and HDAC2 were upregulated in the majority of HCC tissues. The presence of HDAC1 in tumor tissues was correlated with poor tumor differentiation. Notably, HDAC1 expression in adjacent non-tumor hepatic tissues was correlated with the presence of satellite nodules and multiple lesions, suggesting that HDAC1 upregulation within the field of HCC may contribute to tumor spread. Using competing risk regression analysis, we found that increased cancer-specific mortality was significantly associated with HDAC2 expression. Mortality was also increased with high HDAC1 expression. In the liver cancer cell lines, HEP3B, HEPG2, PLC5, and a colorectal cancer cell line, HCT116, the combined knockdown of HDAC1 and HDAC2 increased cell death and reduced cell proliferation as well as colony formation. In contrast, knockdown of either HDAC1 or HDAC2 alone had minimal effects on cell death and proliferation. Taken together, our study suggests that both HDAC1 and HDAC2 exert pro-survival effects in HCC cells, and the combination of isoform-specific HDAC inhibitors against both HDACs may be effective in targeting HCC to reduce mortality.

Proprioceptive acuity predicts muscle co-contraction of the tibalis anterior and gastrocnemius medialis in older adults’ dynamic postural control

Older adults use a different muscle strategy to cope with postural instability, in which they ‘co-contract’ the muscles around the ankle joint. It has been suggested that this is a compensatory response to age-related proprioceptive decline however this view has never been assessed directly. The current study investigated the association between proprioceptive acuity and muscle co-contraction in older adults. We compared muscle activity, by recording surface EMG from the bilateral tibalis anterior and gastrocnemius medialis muscles, in young (aged 18-34) and older adults (aged 65-82) during postural assessment on a fixed and sway-referenced surface at age-equivalent levels of sway. We performed correlations between muscle activity and proprioceptive acuity, which was assessed using an active contralateral matching task. Despite successfully inducing similar levels of sway in the two age groups, older adults still showed higher muscle co-contraction. A stepwise regression analysis showed that proprioceptive acuity measured using variable error was the best predictor of muscle co-contraction in older adults. However, despite suggestions from previous research, proprioceptive error and muscle co-contraction were negatively correlated in older adults, suggesting that better proprioceptive acuity predicts more co-contraction. Overall, these results suggest that although muscle co-contraction may be an age-specific strategy used by older adults, it is not to compensate for age-related proprioceptive deficits.

The notion of space in urban housing markets

O mercado imobiliário tem um papel importante nas economias modernas, tanto a nível macro como a nível micro. Ao nível macro, a construção de habitação representa um sector importante e influente na economia, com efeitos multiplicadores significativos sobre a produção e o emprego. Ao nível micro, uma residência representa o activo mais valioso da maioria dos indivíduos e uma parcela muito relevante da riqueza das famílias. Para estas, o custo e a qualidade das suas habitações influencia directa e indirectamente a sua qualidade de vida. A habitação é por isso mesmo um tema, que avaliado nas suas múltiplas dimensões, se caracteriza por ser bastante complexo, mas também ao mesmo tempo desafiante. De modo a delimitar o objecto de análise do trabalho de investigação, esta tese realça os aspectos de localização e distribuição espacial das habitações urbanas. Será desenvolvido um quadro conceptual e respectiva metodologia para a compreender a estrutura espacial da habitação urbana realçando os três aspectos fundamentais da análise espacial: heterogenidade espacial, dependência espacial e escala espacial. A metodologia, aplicada à área urbana de Aveiro e Ílhavo é baseada numa análise hedónica factorial de preços e na noção não geométrica do espaço. Primeiro, é fixada uma escala territorial e são definidos submercados habitacional. Posteriormente, quer a heterogeneidade quer a dependência espaciais são estudados utilizando métodos econométricos, sem considerar qualquer padrão fixo e conhecido de interações espaciais. Em vez disso, são desenvolvidos novos métodos,tendo como base o modelo hedónico factorial, para inferir sobre os potenciais drivers de difusão espacial no valor de uma habitação. Este modelo, foi aplicado a duas diferentes escalas espaciais, para compreender as preferências dos indivíduos em Aveiro ao escolher os seus locais de residencia, e como estas afectam os preços da habitação. O trabalho empírico, utilizando duas bases de dados de habitação distintas, aplicadas ao mercado de habitação de Aveiro mostram: i) em linha com a literatura, a dificuldade de definir submercados e compreender as inter-relações entre esses mercados; ii) a utilidade de uma abordagem híbrida, combinando análise factorial com regressão; iii) a importância fundamental que o efeito escala espacial desempenha no estudo da heterogeneidade e dos spillovers e, finalmente, iv) uma metodologia inovadora para analisar spillovers sem assumir aprioristicamente uma estrutura espacial específica de difusão espacial. Esta metodologia considera a matriz de pesos espaciais (W) desconhecida e estimatima as interações espaciais dentro e entre submercados habitação.

Application of DPSIR framework integrated with multiple regression model to simulate Guadiana catchment - estuary continuum, south eastern Iberia

Dissertação de Mestrado, Gestão da Água e da Costa, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2010