663 research outputs found
A tale of two sites: how inflammation can reshape the microbiomes of the gut and lungs
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141495/1/jlb0943.pd
Consistent Quantum Counterfactuals
An analysis using classical stochastic processes is used to construct a
consistent system of quantum counterfactual reasoning. When applied to a
counterfactual version of Hardy's paradox, it shows that the probabilistic
character of quantum reasoning together with the ``one framework'' rule
prevents a logical contradiction, and there is no evidence for any mysterious
nonlocal influences. Counterfactual reasoning can support a realistic
interpretation of standard quantum theory (measurements reveal what is actually
there) under appropriate circumstances.Comment: Minor modifications to make it agree with published version. Latex 8
pages, 2 figure
Markov decision analysis of neoadjuvant treatment pathway versus surgery first pathway for resectable pancreatic cancer
Background: Surgery first (SF) versus neoadjuvant approach (NAT) to management of potentially resectable pancreatic ductal adenocarcinoma (PDAC) is controversial. This study is unique in utilizing institutional data to offer Markov decision-analysis of overall treatment pathways for resectable PDAC. Methods: An advanced Markov decision analysis model was constructed and populated with data from a retrospective institutional database. Patients presenting with resectable PDAC from 2008-2012 were included in the SF arm. Those presenting with resectable PDAC from 2012-2016 and treated within NAT pathway populated the NAT arm. Model uncertainties were tested with one and two-way deterministic sensitivity analysis and probabilistic Monte Carlo sensitivity analysis set to 1000 cycles with variables altered between highest and lowest observed values. Results: NAT pathway gave an additional 0.58 QALMs (22.43 vs. 21.85 QALMs). Monte Carlo analysis reported indifference between treatment strategies. One-way deterministic sensitivity analysis showed that probability of resection in the SF pathway must be greater than 0.82, or below 0.72 in NAT pathway, and probability of receiving adjuvant therapy above 0.6 to alter pathway superiority. Two-way deterministic sensitivity analysis demonstrated treatment superiority depended on resection rate in each pathway and receiving adjuvant therapy in SF pathway. Markov cohort analysis demonstrated superiority of neoadjuvant pathway (Table). Conclusions: Optimal treatment pathway remains debatable on an intention-to-treat Markov decision analysis. Markov cohort analysis of treatment received demonstrated benefit with NAT pathway
Comparative biochemical analysis of UHRF proteins reveals molecular mechanisms that uncouple UHRF2 from DNA methylation maintenance
UHRF1 is a histone- and DNA-binding E3 ubiquitin ligase that functions with DNMT1 to maintain mammalian DNA methylation. UHRF1 facilitates DNMT1 recruitment to replicating chromatin through a coordinated mechanism involving histone and DNA recognition and histone ubiquitination. UHRF2 shares structural homology with UHRF1, but surprisingly lacks functional redundancy to facilitate DNA methylation maintenance. Molecular mechanisms uncoupling UHRF2 from DNA methylation maintenance are poorly defined. Through comprehensive and comparative biochemical analysis of recombinant human UHRF1 and UHRF2 reader and writer activities, we reveal conserved modes of histone PTM recognition but divergent DNA binding properties. While UHRF1 and UHRF2 diverge in their affinities toward hemi-methylated DNA, we surprisingly show that both hemi-methylated and hemi-hydroxymethylated DNA oligonucleotides stimulate UHRF2 ubiquitin ligase activity toward histone H3 peptide substrates. This is the first example of an E3 ligase allosterically regulated by DNA hydroxymethylation. However, UHRF2 is not a productive histone E3 ligase toward purified mononucleosomes, suggesting UHRF2 has an intra-domain architecture distinct from UHRF1 that is conformationally constrained when bound to chromatin. Collectively, our studies reveal that uncoupling of UHRF2 from the DNA methylation maintenance program is linked to differences in the molecular readout of chromatin signatures that connect UHRF1 to ubiquitination of histone H3
Report on an all-sky LIGO search for periodic gravitational waves in the S4 data
We report on an all-sky search with the LIGO detectors for periodic
gravitational waves in the frequency range 50-1000 Hz and having a negative
frequency time derivative with magnitude between zero and Hz/s. Data
from the fourth LIGO science run have been used in this search. Three different
semi-coherent methods of summing strain power were applied. Observing no
evidence for periodic gravitational radiation, we report upper limits on strain
amplitude and interpret these limits to constrain radiation from rotating
neutron stars.Comment: 5 pages, 1 figure, presented at Amaldi7, Sydney (July 2007
Searching for stochastic gravitational-wave background with the co-located LIGO interferometers
This paper presents techniques developed by the LIGO Scientific Collaboration
to search for the stochastic gravitational-wave background using the co-located
pair of LIGO interferometers at Hanford, WA. We use correlations between
interferometers and environment monitoring instruments, as well as time-shifts
between two interferometers (described here for the first time) to identify
correlated noise from non-gravitational sources. We veto particularly noisy
frequency bands and assess the level of residual non-gravitational coupling
that exists in the surviving data.Comment: Proceedings paper from the 7th Edoardo Amaldi Conference on
Gravitational Waves, held in Sydney, Australia from 8-14 July 2007. Accepted
to J. Phys.: Conf. Se
Cell-associated bacteria in the human lung microbiome
Abstract
Background
Recent studies have revealed that bronchoalveolar lavage (BAL) fluid contains previously unappreciated communities of bacteria. In vitro and in vivo studies have shown that host inflammatory signals prompt bacteria to disperse from cell-associated biofilms and adopt a virulent free-living phenotype. The proportion of the lung microbiota that is cell-associated is unknown.
Results
Forty-six BAL specimens were obtained from lung transplant recipients and divided into two aliquots: ‘whole BAL’ and ‘acellular BAL,’ the latter processed with a low-speed, short-duration centrifugation step. Both aliquots were analyzed via bacterial 16S rRNA gene pyrosequencing. The BAL specimens represented a wide spectrum of lung health, ranging from healthy and asymptomatic to acutely infected. Bacterial signal was detected in 52% of acellular BAL aliquots, fewer than were detected in whole BAL (96%, p ≤ 0.0001). Detection of bacteria in acellular BAL was associated with indices of acute infection [BAL neutrophilia, high total bacterial (16S) DNA, low community diversity, p < 0.01 for all] and, independently, with low relative abundance of specific taxonomic groups (p < 0.05). When whole and acellular aliquots from the same bronchoscopy were directly compared, acellular BAL contained fewer bacterial species (p < 0.05); whole and acellular BAL similarity was positively associated with evidence of infection and negatively associated with relative abundance of several prominent taxa (p < 0.001). Acellular BAL contained decreased relative abundance of Prevotella spp. (p < 0.05) and Pseudomonas fluorescens (p < 0.05).
Conclusions
We present a novel methodological and analytical approach to the localization of lung microbiota and show that prominent members of the lung microbiome are cell-associated, potentially via biofilms, cell adhesion, or intracellularity.http://deepblue.lib.umich.edu/bitstream/2027.42/111056/1/40168_2014_Article_75.pd
Progress in Interferometry for LISA at JPL
Recent advances at JPL in experimentation and design for LISA interferometry
include the demonstration of Time Delay Interferometry using electronically
separated end stations, a new arm-locking design with improved gain and
stability, and progress in flight readiness of digital and analog electronics
for phase measurements.Comment: 11 pages, 9 figures, LISA 8 Symposium, Stanford University, 201
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Ligand electronic fine-tuning and its repercussion on the photocatalytic activity and mechanistic pathways of the copper-photocatalysed aza-Henry reaction
A family of six structurally related heteroleptic copper(i) complexes of the form of [Cu(N^N)(P^P)]+ bearing a 2,9-dimethyl-1,10-phenanthroline diimine (N^N) ligand and a series of electronically tunable xantphos (P^P) ligands have been synthesized and their optoelectronic properties characterized. The reactivity of these complexes in the copper-photocatalyzed aza-Henry reaction of N-phenyltetrahydroisoquinoline was evaluated, while the related excited state kinetics were comprehensively studied. By subtlety changing the electron-donating properties of the P^P ligands with negligible structural differences, we could tailor the photoredox properties and relate them to the reactivity. Moreover, depending on the exited-state redox potential of the catalysts, the preferred mechanism can shift between reductive quenching, energy transfer and oxidative quenching pathways. A combined study of the structural modulation of copper(i) photocatalysts, optoelectronic properties and photocatalytic reactivity resulted in a clearer understanding of both the rational design of the photocatalyst and the complexity of competing photoinduced electron and energy transfer mechanisms. © The Royal Society of Chemistry
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