4,095 research outputs found
A semi-Markov model for stroke with piecewise-constant hazards in the presence of left, right and interval censoring.
This paper presents a parametric method of fitting semi-Markov models with piecewise-constant hazards in the presence of left, right and interval censoring. We investigate transition intensities in a three-state illness-death model with no recovery. We relax the Markov assumption by adjusting the intensity for the transition from state 2 (illness) to state 3 (death) for the time spent in state 2 through a time-varying covariate. This involves the exact time of the transition from state 1 (healthy) to state 2. When the data are subject to left or interval censoring, this time is unknown. In the estimation of the likelihood, we take into account interval censoring by integrating out all possible times for the transition from state 1 to state 2. For left censoring, we use an Expectation-Maximisation inspired algorithm. A simulation study reflects the performance of the method. The proposed combination of statistical procedures provides great flexibility. We illustrate the method in an application by using data on stroke onset for the older population from the UK Medical Research Council Cognitive Function and Ageing Study
A Suborbital Payload for Soft X-ray Spectroscopy of Extended Sources
We present a suborbital rocket payload capable of performing soft X-ray
spectroscopy on extended sources. The payload can reach resolutions of
~100(lambda/dlambda) over sources as large as 3.25 degrees in diameter in the
17-107 angstrom bandpass. This permits analysis of the overall energy balance
of nearby supernova remnants and the detailed nature of the diffuse soft X-ray
background. The main components of the instrument are: wire grid collimators,
off-plane grating arrays and gaseous electron multiplier detectors. This
payload is adaptable to longer duration orbital rockets given its comparatively
simple pointing and telemetry requirements and an abundance of potential
science targets.Comment: Accepted to Experimental Astronomy, 12 pages plus 1 table and 17
figure
Fixed Effect Estimation of Large T Panel Data Models
This article reviews recent advances in fixed effect estimation of panel data
models for long panels, where the number of time periods is relatively large.
We focus on semiparametric models with unobserved individual and time effects,
where the distribution of the outcome variable conditional on covariates and
unobserved effects is specified parametrically, while the distribution of the
unobserved effects is left unrestricted. Compared to existing reviews on long
panels (Arellano and Hahn 2007; a section in Arellano and Bonhomme 2011) we
discuss models with both individual and time effects, split-panel Jackknife
bias corrections, unbalanced panels, distribution and quantile effects, and
other extensions. Understanding and correcting the incidental parameter bias
caused by the estimation of many fixed effects is our main focus, and the
unifying theme is that the order of this bias is given by the simple formula
p/n for all models discussed, with p the number of estimated parameters and n
the total sample size.Comment: 40 pages, 1 tabl
Omega-3 polyunsaturated fatty acids status and cognitive function in young women
© 2019 The Author(s). Background: Research indicates that low omega-3 polyunsaturated fatty acid (n-3 PUFA) may be associated with decreased cognitive function. This study examined the association between n-3 PUFA status and cognitive function in young Australian women. Methods: This was a secondary outcome analysis of a cross-sectional study that recruited 300 healthy women (18-35 y) of normal weight (NW: BMI 18.5-24.9 kg/m2) or obese weight (OB: BMI ≥30.0 kg/m2). Participants completed a computer-based cognition testing battery (IntegNeuro™) evaluating the domains of impulsivity, attention, information processing, memory and executive function. The Omega-3 Index (O3I) was used to determine n-3 PUFA status (percentage of EPA (20:5n-3) plus DHA (22:6n3) in the red cell membrane) and the participants were divided into O3I tertile groups: T1 6.75%. Potential confounding factors of BMI, inflammatory status (C-reactive Protein), physical activity (total MET-min/wk), alpha1-acid glycoprotein, serum ferritin and hemoglobin, were assessed. Data reported as z-scores (mean ± SD), analyses via ANOVA and ANCOVA. Results: Two hundred ninety-nine women (26.9 ± 5.4 y) completed the study (O3I data, n = 288). The ANOVA showed no overall group differences but a significant group × cognition domain interaction (p < 0.01). Post hoc tests showed that participants in the low O3I tertile group scored significantly lower on attention than the middle group (p = 0.01; ES = 0.45 [0.15-0.74]), while the difference with the high group was borderline significant (p = 0.052; ES = 0.38 [0.09-0.68]). After confounder adjustments, the low group had lower attention scores than both the middle (p = 0.01) and high (p = 0.048) groups. These findings were supported by univariate analyses which found significant group differences for the attention domain only (p = 0.004). Conclusions: Cognitive function in the attention domain was lower in women with lower O3I, but still within normal range. This reduced but normal level of cognition potentially provides a lower baseline from which cognition would decline with age. Further investigation of individuals with low n-3 PUFA status is warranted
Complete mitochondrial DNA sequences provide new insights into the Polynesian motif and the peopling of Madagascar
More than a decade of mitochondrial DNA (mtDNA) studies have given the 'Polynesian motif' renowned status as a marker for tracing the late-Holocene expansion of Austronesian speaking populations. Despite considerable research on the Polynesian motif in Oceania, there has been little equivalent work on the western edge of its expansion - leaving major issues unresolved regarding the motif's evolutionary history. This has also led to considerable uncertainty regarding the settlement of Madagascar. In this study, we assess mtDNA variation in 266 individuals from three Malagasy ethnic groups: the Mikea, Vezo, and Merina. Complete mtDNA genome sequencing reveals a new variant of the Polynesian motif in Madagascar; two coding region mutations define a Malagasy-specific sub-branch. This newly defined 'Malagasy motif' occurs at high frequency in all three ethnic groups (13-50%), and its phylogenetic position, geographic distribution, and estimated age all support a recent origin, but without conclusively identifying a specific source region. Nevertheless, the haplotype's limited diversity, similar to those of other mtDNA haplogroups found in our Malagasy groups, best supports a small number of initial settlers arriving to Madagascar through the same migratory process. Finally, the discovery of this lineage provides a set of new polymorphic positions to help localize the Austronesian ancestors of the Malagasy, as well as uncover the origin and evolution of the Polynesian motif itself
Semiparametric Multivariate Accelerated Failure Time Model with Generalized Estimating Equations
The semiparametric accelerated failure time model is not as widely used as
the Cox relative risk model mainly due to computational difficulties. Recent
developments in least squares estimation and induced smoothing estimating
equations provide promising tools to make the accelerate failure time models
more attractive in practice. For semiparametric multivariate accelerated
failure time models, we propose a generalized estimating equation approach to
account for the multivariate dependence through working correlation structures.
The marginal error distributions can be either identical as in sequential event
settings or different as in parallel event settings. Some regression
coefficients can be shared across margins as needed. The initial estimator is a
rank-based estimator with Gehan's weight, but obtained from an induced
smoothing approach with computation ease. The resulting estimator is consistent
and asymptotically normal, with a variance estimated through a multiplier
resampling method. In a simulation study, our estimator was up to three times
as efficient as the initial estimator, especially with stronger multivariate
dependence and heavier censoring percentage. Two real examples demonstrate the
utility of the proposed method
On the Interface Formation Model for Dynamic Triple Lines
This paper revisits the theory of Y. Shikhmurzaev on forming interfaces as a
continuum thermodynamical model for dynamic triple lines. We start with the
derivation of the balances for mass, momentum, energy and entropy in a
three-phase fluid system with full interfacial physics, including a brief
review of the relevant transport theorems on interfaces and triple lines.
Employing the entropy principle in the form given in [Bothe & Dreyer, Acta
Mechanica, doi:10.1007/s00707-014-1275-1] but extended to this more general
case, we arrive at the entropy production and perform a linear closure, except
for a nonlinear closure for the sorption processes. Specialized to the
isothermal case, we obtain a thermodynamically consistent mathematical model
for dynamic triple lines and show that the total available energy is a strict
Lyapunov function for this system
SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1
BACKGROUND
We have previously identified kinase suppressor of ras-1 (KSR1) as a potential regulatory gene in breast cancer. KSR1, originally described as a novel protein kinase, has a role in activation of mitogen-activated protein kinases. Emerging evidence has shown that KSR1 may have dual functions as an active kinase as well as a scaffold facilitating multiprotein complex assembly. Although efforts have been made to study the role of KSR1 in certain tumour types, its involvement in breast cancer remains unknown.
METHODS
A quantitative mass spectrometry analysis using stable isotope labelling of amino acids in cell culture (SILAC) was implemented to identify KSR1-regulated phosphoproteins in breast cancer. In vitro luciferase assays, co-immunoprecipitation as well as western blotting experiments were performed to further study the function of KSR1 in breast cancer.
RESULTS
Of significance, proteomic analysis reveals that KSR1 overexpression decreases deleted in breast cancer-1 (DBC1) phosphorylation. Furthermore, we show that KSR1 decreases the transcriptional activity of p53 by reducing the phosphorylation of DBC1, which leads to a reduced interaction of DBC1 with sirtuin-1 (SIRT1); this in turn enables SIRT1 to deacetylate p53.
CONCLUSION
Our findings integrate KSR1 into a network involving DBC1 and SIRT1, which results in the regulation of p53 acetylation and its transcriptional activity
The priB Gene of Klebsiella pneumoniae Encodes a 104-Amino Acid Protein That Is Similar in Structure and Function to Escherichia coli PriB
Primosome protein PriB is a single-stranded DNA-binding protein that serves as an accessory factor for PriA helicase-catalyzed origin-independent reinitiation of DNA replication in bacteria. A recent report describes the identification of a novel PriB protein in Klebsiella pneumoniae that is significantly shorter than most sequenced PriB homologs. The K. pneumoniae PriB protein is proposed to comprise 55 amino acid residues, in contrast to E. coli PriB which comprises 104 amino acid residues and has a length that is typical of most sequenced PriB homologs. Here, we report results of a sequence analysis that suggests that the priB gene of K. pneumoniae encodes a 104-amino acid PriB protein, akin to its E. coli counterpart. Furthermore, we have cloned the K. pneumoniae priB gene and purified the 104-amino acid K. pneumoniae PriB protein. Gel filtration experiments reveal that the K. pneumoniae PriB protein is a dimer, and equilibrium DNA binding experiments demonstrate that K. pneumoniae PriB's single-stranded DNA-binding activity is similar to that of E. coli PriB. These results indicate that the PriB homolog of K. pneumoniae is similar in structure and in function to that of E. coli
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