1,462 research outputs found
An efficient grinder for ascospores and mycelium
An efficient grinder for ascospores and myceliu
Bilinear modulation models for seasonal tables of counts
We propose generalized linear models for time or age-time tables of seasonal counts, with the goal of better understanding seasonal patterns in the data. The linear predictor contains a smooth component for the trend and the product of a smooth component (the modulation) and a periodic time series of arbitrary shape (the carrier wave). To model rates, a population offset is added. Two-dimensional trends and modulation are estimated using a tensor product B-spline basis of moderate dimension. Further smoothness is ensured using difference penalties on the rows and columns of the tensor product coefficients. The optimal penalty tuning parameters are chosen based on minimization of a quasi-information criterion. Computationally efficient estimation is achieved using array regression techniques, avoiding excessively large matrices. The model is applied to female death rate in the US due to cerebrovascular diseases and respiratory diseases
The ordered K-theory of a full extension
Let A be a C*-algebra with real rank zero which has the stable weak
cancellation property. Let I be an ideal of A such that I is stable and
satisfies the corona factorization property. We prove that 0->I->A->A/I->0 is a
full extension if and only if the extension is stenotic and K-lexicographic. As
an immediate application, we extend the classification result for graph
C*-algebras obtained by Tomforde and the first named author to the general
non-unital case. In combination with recent results by Katsura, Tomforde, West
and the first author, our result may also be used to give a purely
K-theoretical description of when an essential extension of two simple and
stable graph C*-algebras is again a graph C*-algebra.Comment: Version IV: No changes to the text. We only report that Theorem 4.9
is not correct as stated. See arXiv:1505.05951 for more details. Since
Theorem 4.9 is an application to the main results of the paper, the main
results of this paper are not affected by the error. Version III comments:
Some typos and errors corrected. Some references adde
Modelling trends in digit preference patterns
Digit preference is the habit of reporting certain end digits more often than others. If such a misreporting pattern is a concern, then measures to reduce digit preference can be taken and monitoring changes in digit preference becomes important. We propose a two-dimensional penalized composite link model to estimate the true distributions unaffected by misreporting, the digit preference pattern and a trend in the preference pattern simultaneously. A transfer pattern is superimposed on a series of smooth latent distributions and is modulated along a second dimension. Smoothness of the latent distributions is enforced by a roughness penalty. Ridge regression with an L1-penalty is used to extract the misreporting pattern, and an additional weighted least squares regression estimates the modulating trend vector. Smoothing parameters are selected by the Akaike information criterion. We present a simulation study and apply the model to data on birth weight and on self-reported weight of adults
P-splines with derivative based penalties and tensor product smoothing of unevenly distributed data
The P-splines of Eilers and Marx (1996) combine a B-spline basis with a
discrete quadratic penalty on the basis coefficients, to produce a reduced rank
spline like smoother. P-splines have three properties that make them very
popular as reduced rank smoothers: i) the basis and the penalty are sparse,
enabling efficient computation, especially for Bayesian stochastic simulation;
ii) it is possible to flexibly `mix-and-match' the order of B-spline basis and
penalty, rather than the order of penalty controlling the order of the basis as
in spline smoothing; iii) it is very easy to set up the B-spline basis
functions and penalties. The discrete penalties are somewhat less interpretable
in terms of function shape than the traditional derivative based spline
penalties, but tend towards penalties proportional to traditional spline
penalties in the limit of large basis size. However part of the point of
P-splines is not to use a large basis size. In addition the spline basis
functions arise from solving functional optimization problems involving
derivative based penalties, so moving to discrete penalties for smoothing may
not always be desirable. The purpose of this note is to point out that the
three properties of basis-penalty sparsity, mix-and-match penalization and ease
of setup are readily obtainable with B-splines subject to derivative based
penalization. The penalty setup typically requires a few lines of code, rather
than the two lines typically required for P-splines, but this one off
disadvantage seems to be the only one associated with using derivative based
penalties. As an example application, it is shown how basis-penalty sparsity
enables efficient computation with tensor product smoothers of scattered data
Visualization of Genomic Changes by Segmented Smoothing Using an L0 Penalty
Copy number variations (CNV) and allelic imbalance in tumor tissue can show strong segmentation. Their graphical presentation can be enhanced by appropriate smoothing. Existing signal and scatterplot smoothers do not respect segmentation well. We present novel algorithms that use a penalty on the norm of differences of neighboring values. Visualization is our main goal, but we compare classification performance to that of VEGA
Localized inhibition of protein phosphatase 1 by NUAK1 promotes spliceosome activity and reveals a MYC-sensitive feedback control of transcription.
Deregulated expression of MYC induces a dependence on the NUAK1 kinase, but the molecular mechanisms underlying this dependence have not been fully clarified. Here, we show that NUAK1 is a predominantly nuclear protein that associates with a network of nuclear protein phosphatase 1 (PP1) interactors and that PNUTS, a nuclear regulatory subunit of PP1, is phosphorylated by NUAK1. Both NUAK1 and PNUTS associate with the splicing machinery. Inhibition of NUAK1 abolishes chromatin association of PNUTS, reduces spliceosome activity, and suppresses nascent RNA synthesis. Activation of MYC does not bypass the requirement for NUAK1 for spliceosome activity but significantly attenuates transcription inhibition. Consequently, NUAK1 inhibition in MYC-transformed cells induces global accumulation of RNAPII both at the pause site and at the first exon-intron boundary but does not increase mRNA synthesis. We suggest that NUAK1 inhibition in the presence of deregulated MYC traps non-productive RNAPII because of the absence of correctly assembled spliceosomes
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Local overexpression of the myostatin propeptide increases glucose transporter expression and enhances skeletal muscle glucose disposal
Insulin resistance (IR) in skeletal muscle is a prerequisite for type 2 diabetes and is often associated with obesity. IR also develops alongside muscle atrophy in older individuals in sarcopenic obesity. The molecular defects that underpin this syndrome are not well characterized, and there is no licensed treatment. Deletion of the transforming growth factor-β family member myostatin, or sequestration of the active peptide by overexpression of the myostatin propeptide/latency-associated peptide (ProMyo) results in both muscle hypertrophy and reduced obesity and IR. We aimed to establish whether local myostatin inhibition would have a paracrine/autocrine effect to enhance glucose disposal beyond that simply generated by increased muscle mass, and the mechanisms involved. We directly injected adeno-associated virus expressing ProMyo in right tibialis cranialis/extensor digitorum longus muscles of rats and saline in left muscles and compared the effects after 17 days. Both test muscles were increased in size (by 7 and 11%) and showed increased radiolabeled 2-deoxyglucose uptake (26 and 47%) and glycogen storage (28 and 41%) per unit mass during an intraperitoneal glucose tolerance test. This was likely mediated through increased membrane protein levels of GLUT1 (19% higher) and GLUT4 (63% higher). Interestingly, phosphorylation of phosphoinositol 3-kinase signaling intermediates and AMP-activated kinase was slightly decreased, possibly because of reduced expression of insulin-like growth factor-I in these muscles. Thus, myostatin inhibition has direct effects to enhance glucose disposal in muscle beyond that expected of hypertrophy alone, and this approach may offer potential for the therapy of IR syndrome
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