1,273 research outputs found

    Balson: Bayesian least squares optimization with nonnegative L1-Norm constraint

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    Β© 2018 IEEE. A Bayesian approach termed the BAyesian Least Squares Optimization with Nonnegative L1-norm constraint (BALSON) is proposed. The error distribution of data fitting is described by Gaussian likelihood. The parameter distribution is assumed to be a Dirichlet distribution. With the Bayes rule, searching for the optimal parameters is equivalent to finding the mode of the posterior distribution. In order to explicitly characterize the nonnegative L1-norm constraint of the parameters, we further approximate the true posterior distribution by a Dirichlet distribution. We estimate the moments of the approximated Dirichlet posterior distribution by sampling methods. Four sampling methods have been introduced and implemented. With the estimated posterior distributions, the original parameters can be effectively reconstructed in polynomial fitting problems, and the BALSON framework is found to perform better than conventional methods

    Genetic Code Mutations: The Breaking of a Three Billion Year Invariance

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    The genetic code has been unchanging for some three billion years in its canonical ensemble of encoded amino acids, as indicated by the universal adoption of this ensemble by all known organisms. Code mutations beginning with the encoding of 4-fluoro-Trp by Bacillus subtilis, initially replacing and eventually displacing Trp from the ensemble, first revealed the intrinsic mutability of the code. This has since been confirmed by a spectrum of other experimental code alterations in both prokaryotes and eukaryotes. To shed light on the experimental conversion of a rigidly invariant code to a mutating code, the present study examined code mutations determining the propagation of Bacillus subtilis on Trp and 4-, 5- and 6-fluoro-tryptophans. The results obtained with the mutants with respect to cross-inhibitions between the different indole amino acids, and the growth effects of individual nutrient withdrawals rendering essential their biosynthetic pathways, suggested that oligogenic barriers comprising sensitive proteins which malfunction with amino acid analogues provide effective mechanisms for preserving the invariance of the code through immemorial time, and mutations of these barriers open up the code to continuous change

    Prognostic relevance of a T-type calcium channels gene signature in solid tumours: A correlation ready for clinical validation

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    BackgroundT-type calcium channels (TTCCs) mediate calcium influx across the cell membrane. TTCCs regulate numerous physiological processes including cardiac pacemaking and neuronal activity. In addition, they have been implicated in the proliferation, migration and differentiation of tumour tissues. Although the signalling events downstream of TTCC-mediated calcium influx are not fully elucidated, it is clear that variations in the expression of TTCCs promote tumour formation and hinder response to treatment.MethodsWe examined the expression of TTCC genes (all three subtypes; CACNA-1G, CACNA-1H and CACNA-1I) and their prognostic value in three major solid tumours (i.e. gastric, lung and ovarian cancers) via a publicly accessible database.ResultsIn gastric cancer, expression of all the CACNA genes was associated with overall survival (OS) among stage I-IV patients (all pConclusionsAlterations in CACNA gene expression are linked to tumour prognosis. Gastric cancer represents the most promising setting for further evaluation

    Uneven splitting-ratio 1x2 multimode interference splitters based on silicon wire waveguides

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    Two types of 1x2 multi-mode interference (MMI) splitters with splitting ratios of 85:15 and 72:28 are designed. On the basis of a numerical simulation, an optimal length of the MMI section is obtained. Subsequently, the devices are fabricated and tested. The footprints of the rectangular MMI regions are only 3x18.2 and 3x14.3 (mu m). The minimum excess losses are 1.4 and 1.1 dB. The results of the test on the splitting ratios are consistent with designed values. The devices can be applied in ultra-compact photonic integrated circuits to realize the "tap" function

    Enhanced insulin sensitivity associated with provision of mono and polyunsaturated fatty acids in skeletal muscle cells involves counter modulation of PP2A

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    International audienceAims/Hypothesis: Reduced skeletal muscle insulin sensitivity is a feature associated with sustained exposure to excess saturated fatty acids (SFA), whereas mono and polyunsaturated fatty acids (MUFA and PUFA) not only improve insulin sensitivity but blunt SFA-induced insulin resistance. The mechanisms by which MUFAs and PUFAs institute these favourable changes remain unclear, but may involve stimulating insulin signalling by counter-modulation/repression of protein phosphatase 2A (PP2A). This study investigated the effects of oleic acid (OA; a MUFA), linoleic acid (LOA; a PUFA) and palmitate (PA; a SFA) in cultured myotubes and determined whether changes in insulin signalling can be attributed to PP2A regulation. Principal Findings: We treated cultured skeletal myotubes with unsaturated and saturated fatty acids and evaluated insulin signalling, phosphorylation and methylation status of the catalytic subunit of PP2A. Unlike PA, sustained incubation of rat or human myotubes with OA or LOA significantly enhanced Akt-and ERK1/2-directed insulin signalling. This was not due to heightened upstream IRS1 or PI3K signalling nor to changes in expression of proteins involved in proximal insulin signalling, but was associated with reduced dephosphorylation/inactivation of Akt and ERK1/2. Consistent with this, PA reduced PP2Ac demethylation and tyrosine 307 phosphorylation-events associated with PP2A activation. In contrast, OA and LOA strongly opposed these PA-induced changes in PP2Ac thus exerting a repressive effect on PP2A.Conclusions/Interpretation: Beneficial gains in insulin sensitivity and the ability of unsaturated fatty acids to oppose palmitate-induced insulin resistance in muscle cells may partly be accounted for by counter-modulation of PP2A

    Interleukin-1Ξ² sequesters hypoxia inducible factor 2Ξ± to the primary cilium.

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    BACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1Ξ² (IL-1Ξ²). We have also shown the primary cilium elongates in response to IL-1Ξ² exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2Ξ±). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1Ξ²-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2Ξ± expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2Ξ± in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFΞ± transcription activity or rescue of basal HIF-2Ξ± expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2Ξ± expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2Ξ± provides negative regulation of HIF-2Ξ± expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation

    MBA: a literature mining system for extracting biomedical abbreviations

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    <p>Abstract</p> <p>Background</p> <p>The exploding growth of the biomedical literature presents many challenges for biological researchers. One such challenge is from the use of a great deal of abbreviations. Extracting abbreviations and their definitions accurately is very helpful to biologists and also facilitates biomedical text analysis. Existing approaches fall into four broad categories: rule based, machine learning based, text alignment based and statistically based. State of the art methods either focus exclusively on acronym-type abbreviations, or could not recognize rare abbreviations. We propose a systematic method to extract abbreviations effectively. At first a scoring method is used to classify the abbreviations into acronym-type and non-acronym-type abbreviations, and then their corresponding definitions are identified by two different methods: text alignment algorithm for the former, statistical method for the latter.</p> <p>Results</p> <p>A literature mining system MBA was constructed to extract both acronym-type and non-acronym-type abbreviations. An abbreviation-tagged literature corpus, called Medstract gold standard corpus, was used to evaluate the system. MBA achieved a recall of 88% at the precision of 91% on the Medstract gold-standard EVALUATION Corpus.</p> <p>Conclusion</p> <p>We present a new literature mining system MBA for extracting biomedical abbreviations. Our evaluation demonstrates that the MBA system performs better than the others. It can identify the definition of not only acronym-type abbreviations including a little irregular acronym-type abbreviations (e.g., <CNS1, cyclophilin seven suppressor>), but also non-acronym-type abbreviations (e.g., <Fas, CD95>).</p

    More than a century of bathymetric observations and present-day shallow sediment characterization in Belfast Bay, Maine, USA: implications for pockmark field longevity

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    This paper is not subject to U.S. copyright. The definitive version was published in Geo-Marine Letters 31 (2011): 237-248, doi:10.1007/s00367-011-0228-0.Mechanisms and timescales responsible for pockmark formation and maintenance remain uncertain, especially in areas lacking extensive thermogenic fluid deposits (e.g., previously glaciated estuaries). This study characterizes seafloor activity in the Belfast Bay, Maine nearshore pockmark field using (1) three swath bathymetry datasets collected between 1999 and 2008, complemented by analyses of shallow box-core samples for radionuclide activity and undrained shear strength, and (2) historical bathymetric data (report and smooth sheets from 1872, 1947, 1948). In addition, because repeat swath bathymetry surveys are an emerging data source, we present a selected literature review of recent studies using such datasets for seafloor change analysis. This study is the first to apply the method to a pockmark field, and characterizes macro-scale (>5 m) evolution of tens of square kilometers of highly irregular seafloor. Presence/absence analysis yielded no change in pockmark frequency or distribution over a 9-year period (1999–2008). In that time pockmarks did not detectably enlarge, truncate, elongate, or combine. Historical data indicate that pockmark chains already existed in the 19th century. Despite the lack of macroscopic changes in the field, near-bed undrained shear-strength values of less than 7 kPa and scattered downcore 137Cs signatures indicate a highly disturbed setting. Integrating these findings with independent geophysical and geochemical observations made in the pockmark field, it can be concluded that (1) large-scale sediment resuspension and dispersion related to pockmark formation and failure do not occur frequently within this field, and (2) pockmarks can persevere in a dynamic estuarine setting that exhibits minimal modern fluid venting. Although pockmarks are conventionally thought to be long-lived features maintained by a combination of fluid venting and minimal sediment accumulation, this suggests that other mechanisms may be equally active in maintaining such irregular seafloor morphology. One such mechanism could be upwelling within pockmarks induced by near-bed currents.Graduate support for Brothers came from a Maine Economic Improvement Fund Dissertation Fellowship

    Electron quantum metamaterials in van der Waals heterostructures

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    In recent decades, scientists have developed the means to engineer synthetic periodic arrays with feature sizes below the wavelength of light. When such features are appropriately structured, electromagnetic radiation can be manipulated in unusual ways, resulting in optical metamaterials whose function is directly controlled through nanoscale structure. Nature, too, has adopted such techniques -- for example in the unique coloring of butterfly wings -- to manipulate photons as they propagate through nanoscale periodic assemblies. In this Perspective, we highlight the intriguing potential of designer sub-electron wavelength (as well as wavelength-scale) structuring of electronic matter, which affords a new range of synthetic quantum metamaterials with unconventional responses. Driven by experimental developments in stacking atomically layered heterostructures -- e.g., mechanical pick-up/transfer assembly -- atomic scale registrations and structures can be readily tuned over distances smaller than characteristic electronic length-scales (such as electron wavelength, screening length, and electron mean free path). Yet electronic metamaterials promise far richer categories of behavior than those found in conventional optical metamaterial technologies. This is because unlike photons that scarcely interact with each other, electrons in subwavelength structured metamaterials are charged, and strongly interact. As a result, an enormous variety of emergent phenomena can be expected, and radically new classes of interacting quantum metamaterials designed
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