A kepstrum approach to filtering, smoothing and prediction with application to speech enhancement

A kepstrum (or complex-cepstrum) approach to minimum-phase Wiener filtering of stationary scalar processes is proposed and solved for the case of signal plus coloured noise, where the noise possibly includes a white-noise component. A general solution is found in an innovations form. The spectral factorization of the noise model and of the signal-plus-noise model required for the solution are determined from data using the kepstrum technique with the fast Fourier transform. This approach avoids dependence on any form of multidimensional state-space or polynomial-based model and so avoids use of recursive parameter estimation or of Diophantine equations

Generating intrafusal skeletal muscle fibres in vitro: Current state of the art and future challenges

Intrafusal fibres are a specialised cell population in skeletal muscle, found within the muscle spindle. These fibres have a mechano-sensory capacity, forming part of the monosynaptic stretch-reflex arc, a key component responsible for proprioceptive function. Impairment of proprioception and associated dysfunction of the muscle spindle is linked with many neuromuscular diseases. Research to-date has largely been undertaken in vivo or using ex vivo preparations. These studies have provided a foundation for our understanding of muscle spindle physiology, however, the cellular and molecular mechanisms which underpin physiological changes are yet to be fully elucidated. Therefrom, the use of in vitro models has been proposed, whereby intrafusal fibres can be generated de novo. Although there has been progress, it is predominantly a developing and evolving area of research. This narrative review presents the current state of art in this area and proposes the direction of future work, with the aim of providing novel pre-clinical and clinical applications

Structural Change for a Post-Growth Economy: Investigating the Relationship between Embodied Energy Intensity and Labour Productivity

Post-growth economists propose structural changes towards labour-intensive services, such as care or education, to make our economy more sustainable by providing meaningful work and reducing the environmentally damaging production of material goods. Our study investigates the assumption underlying such proposals. Using a multi-regional input-output model we compare the embodied energy intensity and embodied labour productivity across economic sectors in the UK and Germany between 1995 and 2011. We identify five labour-intensive service sectors, which combine low embodied energy intensity with low growth in embodied labour productivity. However, despite their lower embodied energy intensities, our results indicate that large structural changes towards these sectors would only lead to small reductions in energy footprints. Our results also suggest that labour-intensive service sectors in the UK have been characterised by higher rates of price inflation than other sectors. This supports suggestions from the literature that labour-intensive services face challenges from increasing relative prices and costs. We do not find similar results for Germany, which is the result of low overall growth in embodied labour productivity and prices. This highlights that structural change is closely associated with economic growth, which raises the question of how structural changes can be achieved in a non-growing economy

Neuregulin 1 Drives Morphological and Phenotypical Changes in C2C12 Myotubes: Towards De Novo Formation of Intrafusal Fibres In Vitro

Muscle spindles are sensory organs that detect and mediate both static and dynamic muscle stretch and monitor muscle position, through a specialised cell population, termed intrafusal fibres. It is these fibres that provide a key contribution to proprioception and muscle spindle dysfunction is associated with multiple neuromuscular diseases, aging and nerve injuries. To date, there are few publications focussed on de novo generation and characterisation of intrafusal muscle fibres in vitro. To this end, current models of skeletal muscle focus on extrafusal fibres and lack an appreciation for the afferent functions of the muscle spindle. The goal of this study was to produce and define intrafusal bag and chain myotubes from differentiated C2C12 myoblasts, utilising the addition of the developmentally associated protein, Neuregulin 1 (Nrg-1). Intrafusal bag myotubes have a fusiform shape and were assigned using statistical morphological parameters. The model was further validated using immunofluorescent microscopy and western blot analysis, directed against an extensive list of putative intrafusal specific markers, as identified in vivo. The addition of Nrg-1 treatment resulted in a 5-fold increase in intrafusal bag myotubes (as assessed by morphology) and increased protein and gene expression of the intrafusal specific transcription factor, Egr3. Surprisingly, Nrg-1 treated myotubes had significantly reduced gene and protein expression of many intrafusal specific markers and showed no specificity towards intrafusal bag morphology. Another novel finding highlights a proliferative effect for Nrg-1 during the serum starvation-initiated differentiation phase, leading to increased nuclei counts, paired with less myotube area per myonuclei. Therefore, despite no clear collective evidence for specific intrafusal development, Nrg-1 treated myotubes share two inherent characteristics of intrafusal fibres, which contain increased satellite cell numbers and smaller myonuclear domains compared with their extrafusal neighbours. This research represents a minimalistic, monocellular C2C12 model for progression towards de novo intrafusal skeletal muscle generation, with the most extensive characterisation to date. Integration of intrafusal myotubes, characteristic of native, in vivo intrafusal skeletal muscle into future biomimetic tissue engineered models could provide platforms for developmental or disease state studies, pre-clinical screening, or clinical applications

Outsourcing or efficiency? Investigating the decline in final energy consumption in the UK productive sectors

Over the past two decades reductions in the final energy consumption of the productive sectors (industry, public administration, commercial services and agriculture), have made important contributions to overall reductions in UK final energy consumption. This study investigates the drivers of the reductions in final energy consumption in the UK productive sectors between 1997 and 2013 using a decomposition analysis that incorporates two novel approaches. Firstly, it uses results from a multi-regional input-output model to investigate how much of the structural change in the economy has been driven by outsourcing production overseas. Secondly, it utilises energy conversion chain analysis to determine how much increases in the conversion efficiency from final energy to useful exergy have contributed to improvements in final energy intensity. In aggregate all energy savings from structural change are attributed to outsourcing. Improvements in the conversion efficiency produced savings of a similar size. However energy savings from both factors have stalled since 2009. Improvements in useful exergy intensity, the useful exergy used per unit of monetary output, provided the biggest share of energy savings, but these savings are concentrated in a few sectors and rarely lead to absolute reductions in final energy use. All of this suggests that a return to the rates of energy reduction seen between 2001 and 2009 should not be taken for granted and that active policy interventions might be required to achieve further reductions

Entangled Mechanical Oscillators

Hallmarks of quantum mechanics include superposition and entanglement. In the context of large complex systems, these features should lead to situations like Schrodinger's cat, which exists in a superposition of alive and dead states entangled with a radioactive nucleus. Such situations are not observed in nature. This may simply be due to our inability to sufficiently isolate the system of interest from the surrounding environment -- a technical limitation. Another possibility is some as-of-yet undiscovered mechanism that prevents the formation of macroscopic entangled states. Such a limitation might depend on the number of elementary constituents in the system or on the types of degrees of freedom that are entangled. One system ubiquitous to nature where entanglement has not been previously demonstrated is distinct mechanical oscillators. Here we demonstrate deterministic entanglement of separated mechanical oscillators, consisting of the vibrational states of two pairs of atomic ions held in different locations. We also demonstrate entanglement of the internal states of an atomic ion with a distant mechanical oscillator.Comment: 7 pages, 2 figure

Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

Background/Aims: The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases. Methods: Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study. Results: The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18). Conclusion: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC. Copyright (C) 2011 S. Karger AG, Base

Bell Correlations and the Common Future

Reichenbach's principle states that in a causal structure, correlations of classical information can stem from a common cause in the common past or a direct influence from one of the events in correlation to the other. The difficulty of explaining Bell correlations through a mechanism in that spirit can be read as questioning either the principle or even its basis: causality. In the former case, the principle can be replaced by its quantum version, accepting as a common cause an entangled state, leaving the phenomenon as mysterious as ever on the classical level (on which, after all, it occurs). If, more radically, the causal structure is questioned in principle, closed space-time curves may become possible that, as is argued in the present note, can give rise to non-local correlations if to-be-correlated pieces of classical information meet in the common future --- which they need to if the correlation is to be detected in the first place. The result is a view resembling Brassard and Raymond-Robichaud's parallel-lives variant of Hermann's and Everett's relative-state formalism, avoiding "multiple realities."Comment: 8 pages, 5 figure

A survey of orphan enzyme activities

<p>Abstract</p> <p>Background</p> <p>Using computational database searches, we have demonstrated previously that no gene sequences could be found for at least 36% of enzyme activities that have been assigned an Enzyme Commission number. Here we present a follow-up literature-based survey involving a statistically significant sample of such "orphan" activities. The survey was intended to determine whether sequences for these enzyme activities are truly unknown, or whether these sequences are absent from the public sequence databases but can be found in the literature.</p> <p>Results</p> <p>We demonstrate that for ~80% of sampled orphans, the absence of sequence data is bona fide. Our analyses further substantiate the notion that many of these enzyme activities play biologically important roles.</p> <p>Conclusion</p> <p>This survey points toward significant scientific cost of having such a large fraction of characterized enzyme activities disconnected from sequence data. It also suggests that a larger effort, beginning with a comprehensive survey of all putative orphan activities, would resolve nearly 300 artifactual orphans and reconnect a wealth of enzyme research with modern genomics. For these reasons, we propose that a systematic effort to identify the cognate genes of orphan enzymes be undertaken.</p

Novel associations for hypothyroidism include known autoimmune risk loci

Hypothyroidism is the most common thyroid disorder, affecting about 5% of the general population. Here we present the first large genome-wide association study of hypothyroidism, in 2,564 cases and 24,448 controls from the customer base of 23andMe, Inc., a personal genetics company. We identify four genome-wide significant associations, two of which are well known to be involved with a large spectrum of autoimmune diseases: rs6679677 near _PTPN22_ and rs3184504 in _SH2B3_ (p-values 3.5e-13 and 3.0e-11, respectively). We also report associations with rs4915077 near _VAV3_ (p-value 8.3e-11), another gene involved in immune function, and rs965513 near _FOXE1_ (p-value 3.1e-14). Of these, the association with _PTPN22_ confirms a recent small candidate gene study, and _FOXE1_ was previously known to be associated with thyroid-stimulating hormone (TSH) levels. Although _SH2B3_ has been previously linked with a number of autoimmune diseases, this is the first report of its association with thyroid disease. The _VAV3_ association is novel. These results suggest heterogeneity in the genetic etiology of hypothyroidism, implicating genes involved in both autoimmune disorders and thyroid function. Using a genetic risk profile score based on the top association from each of the four genome-wide significant regions in our study, the relative risk between the highest and lowest deciles of genetic risk is 2.1