Bayesian penalized model for classification and selection of functional predictors using longitudinal MRI data from ADNI

The main goal of this paper is to employ longitudinal trajectories in a significant number of sub-regional brain volumetric MRI data as statistical predictors for Alzheimer's disease (AD) classification. We use logistic regression in a Bayesian framework that includes many functional predictors. The direct sampling of regression coefficients from the Bayesian logistic model is difficult due to its complicated likelihood function. In high-dimensional scenarios, the selection of predictors is paramount with the introduction of either spike-and-slab priors, non-local priors, or Horseshoe priors. We seek to avoid the complicated Metropolis-Hastings approach and to develop an easily implementable Gibbs sampler. In addition, the Bayesian estimation provides proper estimates of the model parameters, which are also useful for building inference. Another advantage of working with logistic regression is that it calculates the log of odds of relative risk for AD compared to normal control based on the selected longitudinal predictors, rather than simply classifying patients based on cross-sectional estimates. Ultimately, however, we combine approaches and use a probability threshold to classify individual patients. We employ 49 functional predictors consisting of volumetric estimates of brain sub-regions, chosen for their established clinical significance. Moreover, the use of spike-and-slab priors ensures that many redundant predictors are dropped from the model

The mutation that makes Escherichia coli resistant to λ P gene-mediated host lethality is located within the DNA initiator gene dnaA of the bacterium

Earlier, we reported that the bacteriophage λ P gene product is lethal to Escherichia coli, and the E. coli rpl mutants are resistant to this λ P gene-mediated lethality. In this paper, we show that under the λ P gene-mediated lethal condition, the host DNA synthesis is inhibited at the initiation step. The rpl8 mutation maps around the 83 min position in the E. coli chromosome and is 94% linked with the dnaA gene. The rpl8 mutant gene has been cloned in a plasmid. This plasmid clone can protect the wild-type E. coli from λ P gene-mediated killing and complements E. coli dnaAts46 at 42° C. Also, starting with the wild-type dnaA gene in a plasmid, the rpl-like mutations have been isolated by in vitro mutagenesis. DNA sequencing data show that each of the rpl8, rpl12 and rpl14 mutations has changed a single base in the dnaA gene, which translates into the amino acid changes N313T, Y200N, and S246T respectively within the DnaA protein. These results have led us to conclude that the rpl mutations, which make E. coli resistant to λ P gene-mediated host lethality, are located within the DNA initiator gene dnaA of the host

Inhibition of a transcriptional pause by RNA Anchoring to RNA polymerase

We describe a mechanism by which nascent RNA inhibits transcriptional pausing. PutL RNA of bacteriophage HK022 suppresses transcription termination at downstream terminators and pausing within a nearby U-rich sequence. In vitro transcription and footprinting assays reveal that this pausing results from backtracking of RNA polymerase and that binding of nascent putL RNA to polymerase limits backtracking by restricting re-entry of the transcript into the RNA exit channel. The restriction is local and relaxes as the transcript elongates. Our results suggest that putL RNA binds to the surface of polymerase close to the RNA exit channel, a region that includes amino acid residues important for antitermination. Although binding is essential for antipausing and antitermination, these two activities of put differ: antipausing is limited to the immediate vicinity of the putL site, but antitermination is not. We propose that RNA anchoring to the elongation complex is a widespread mechanism of pause regulation

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Effect of Encapsulation of Curcumin in Polymeric Nanoparticles: How Efficient to Control ESIPT Process?

This paper demonstrates the photophysics of curcumin inside polymeric nanoparticles (NPs), which are being recently used as targeted drug delivery vehicles. For this purpose, we have prepared three polymeric NPs by ultrasonication method from three well-defined water-insoluble random copolymers. These copolymers having various degrees of hydrophobicity were synthesized via reversible addition–fragmentation transfer (RAFT) method using styrene and three different functional monomers, namely, 2-hydroxyethyl acrylate, 4-formylphenyl acrylate, and 4-vinylbenzyl chloride. The photophysics of the curcumin molecules inside the polymeric NPs have been monitored by applying tools like steady state and time-resolved fluorescence spectroscopy. An increase in fluorescence intensity along with an increase in the lifetime values indicated a perturbation of the excited state intramolecular proton transfer (ESIPT) process of curcumin inside the polymeric NPs