4,334 research outputs found
Label-free proteomics assisted by affinity enrichment for elucidating the chemical reactivity of the liver mitochondrial proteome toward adduction by the lipid electrophile 4-hydroxy-2-nonenal (HNE)
The analysis of oxidative stress-induced post-translational modifications remains challenging due to the chemical diversity of these modifications, the possibility of the presence of positional isomers and the low stoichiometry of the modified proteins present in a cell or tissue proteome. Alcoholic liver disease (ALD) is a multifactorial disease in which mitochondrial dysfunction and oxidative stress have been identified as being critically involved in the progression of the disease from steatosis to cirrhosis. Ethanol metabolism leads to increased levels of reactive oxygen species (ROS), glutathione depletion and lipid peroxidation. Posttranslational modification of proteins by electrophilic products of lipid peroxidation has been associated with governing redox-associated signaling mechanisms, but also as contributing to protein dysfunction leading to organelle and liver injury. In particular the prototypical α,β-unsaturated aldehyde, 4-hydroxy-2-nonenal (HNE), has been extensively studied as marker of increased oxidative stress in hepatocytes. In this study, we combined a LC-MS label-free quantification method and affinity enrichment to assess the dose-dependent insult by HNE on the proteome of rat liver mitochondria. We used a carbonyl-selective probe, the ARP probe, to label HNE-protein adducts and to perform affinity capture at the protein level. Using LC-MS to obtain protein abundance estimates, a list of protein targets was obtained with increasing concentration of HNE used in the exposure studies. In parallel, we performed affinity capture at the peptide level to acquire site-specific information. Examining the concentration-dependence of the protein modifications, we observed distinct reactivity profiles for HNE-protein adduction. Pathway analysis indicated that proteins associated with metabolic processes, including amino acid, fatty acid, and glyoxylate and dicarboxylate metabolism, bile acid synthesis and TCA cycle, showed enhanced reactivity to HNE adduction. Whereas, proteins associated with oxidative phosphorylation displayed retardation toward HNE adduction. We provide a list of 31 protein targets with a total of 61 modification sites that may guide future targeted LC-MS assays to monitor disease progression and/or intervention in preclinical models of ALD and possibly other liver diseases with an oxidative stress component
Perspectives of staff nurses of the reasons for and the nature of patient-initiated call lights: an exploratory survey study in four USA hospitals
<p>Abstract</p> <p>Background</p> <p>Little research has been done on patient call light use and staff response time, which were found to be associated with inpatient falls and satisfaction. Nurses' perspectives may moderate or mediate the aforementioned relationships. This exploratory study intended to understand staff's perspectives about call lights, staff responsiveness, and the reasons for and the nature of call light use. It also explored differences among hospitals and identified significant predictors of the nature of call light use.</p> <p>Methods</p> <p>This cross-sectional, multihospital survey study was conducted from September 2008 to January 2009 in four hospitals located in the Midwestern region of the United States. A brief survey was used. All 2309 licensed and unlicensed nursing staff members who provide direct patient care in 27 adult care units were invited to participate. A total of 808 completed surveys were retrieved for an overall response rate of 35%. The SPSS 16.0 Window version was used. Descriptive and binary logistic regression analyses were conducted.</p> <p>Results</p> <p>The primary reasons for patient-initiated calls were for toileting assistance, pain medication, and intravenous problems. Toileting assistance was the leading reason. Each staff responded to 6 to 7 calls per hour and a call was answered within 4 minutes (estimated). 49% of staff perceived that patient-initiated calls mattered to patient safety. 77% agreed that that these calls were meaningful. 52% thought that these calls required the attention of nursing staff. 53% thought that answering calls prevented them from doing the critical aspects of their role. Staff's perceptions about the nature of calls varied across hospitals. Junior staff tended to overlook the importance of answering calls. A nurse participant tended to perceive calls as more likely requiring nursing staff's attention than a nurse aide participant.</p> <p>Conclusions</p> <p>If answering calls was a high priority among nursing tasks, staff would perceive calls as being important, requiring nursing staff's attention, and being meaningful. Therefore, answering calls should not be perceived as preventing staff from doing the critical aspects of their role. Additional efforts are necessary to reach the ideal or even a reasonable level of patient safety-first practice in current hospital environments.</p
Modeling and Evaluating of Business Revenue Models under Different Product Life Cycles Using System Dynamics Simulation
Business revenue modelling is one of the important aspects of enterprise planning to create values for enterprises. In this study, we construct a system dynamics simulation model to evaluate various business revenue models applied to e-platforms. Machining tools industry is investigated as a case study. Products with different life cycles are examined as applying different business models. Computational experiments are conducted and results are discussed. Specific research issues/contributions of the study include: 1. To propose four effective business revenue models in such an industry. 2. To evaluate the proposed business revenue models as well as their advantages/disadvantages by a system dynamics simulation. 3. To address managerial implications of these business revenue models to the industry. As a conclusion to our research, we show that: (i) Firms with products under growth or mature stage of life cycle adopt/switch appropriate business revenue models conforming to their requirements in different stages and result in high performance outcomes than those remaining in a single business revenue model. (ii) Business revenue models represented by causal loops of system dynamics and examined by system simulation can capture not only steady states but transient states of business activities. By taking advantages of the proposed approach, managers can thus efficiently make right decisions for reducing time and cost
Obstructive sleep apnea as an independent predictor of postoperative delirium and pain: Protocol for an observational study of a surgical cohort [version 2; referees: 2 approved]
Introduction: Postoperative delirium and pain are common complications in adults, and are difficult both to prevent and treat. Obstructive sleep apnea (OSA) is prevalent in surgical patients, and has been suggested to be a risk factor for postoperative delirium and pain. OSA also might impact pain perception, and alter pain medication requirements. This protocol describes an observational study, with the primary aim of testing whether OSA is an independent predictor of postoperative complications, focusing on (i) postoperative incident delirium and (ii) acute postoperative pain severity. We secondarily hypothesize that compliance with prescribed treatment for OSA (typically continuous positive airway pressure or CPAP) might decrease the risk of delirium and the severity of pain. Methods and analysis: We will include data from patients who have been enrolled into three prospective studies: ENGAGES, PODCAST, and SATISFY-SOS. All participants underwent general anesthesia for a non-neurosurgical inpatient operation, and had a postoperative hospital stay of at least one day at Barnes Jewish Hospital in St. Louis, Missouri, from February 2013 to May 2018. Â Patients included in this study have been assessed for postoperative delirium and pain severity as part of the parent studies. In the current study, determination of delirium diagnosis will be based on the Confusion Assessment Method, and the Visual Analogue Pain Scale will be used for pain severity. Data on OSA diagnosis, OSA risk and compliance with treatment will be obtained from the preoperative assessment record. Other variables that are candidate risk factors for delirium and pain will also be extracted from this record. We will use logistic regression to test whether OSA independently predicts postoperative delirium and linear regression to assess OSAs relationship to acute pain severity. We will conduct secondary analyses with subgroups to explore whether these relationships are modified by compliance with OSA treatment.</ns4:p
The Pfaffian solution of a dimer-monomer problem: Single monomer on the boundary
We consider the dimer-monomer problem for the rectangular lattice. By mapping
the problem into one of close-packed dimers on an extended lattice, we rederive
the Tzeng-Wu solution for a single monomer on the boundary by evaluating a
Pfaffian. We also clarify the mathematical content of the Tzeng-Wu solution by
identifying it as the product of the nonzero eigenvalues of the Kasteleyn
matrix.Comment: 4 Pages to appear in the Physical Review E (2006
HAPMAP: a computer program for the linkage analysis of haploids.
The development of technology for the detection of variations in DNA sequence is permitting the rapid mapping of the genomes of many organisms
Influence of realistic parameters on state-of-the-art LWFA experiments
We examine the influence of non-ideal plasma-density and non-Gaussian
transverse laser-intensity profiles in the laser wakefield accelerator
analytically and numerically. We find that the characteristic amplitude and
scale length of longitudinal density fluctuations impacts on the final energies
achieved by electron bunches. Conditions that minimize the role of the
longitudinal plasma density fluctuations are found. The influence of higher
order Laguerre-Gaussian laser pulses is also investigated. We find that higher
order laser modes typically lead to lower energy gains. Certain combinations of
higher order modes may, however, lead to higher electron energy gains.Comment: 16 pages, 6 figures; Accepted for publication in Plasma Physics and
Controlled Fusio
Theory of resistor networks: The two-point resistance
The resistance between arbitrary two nodes in a resistor network is obtained
in terms of the eigenvalues and eigenfunctions of the Laplacian matrix
associated with the network. Explicit formulas for two-point resistances are
deduced for regular lattices in one, two, and three dimensions under various
boundary conditions including that of a Moebius strip and a Klein bottle. The
emphasis is on lattices of finite sizes. We also deduce summation and product
identities which can be used to analyze large-size expansions of two-and-higher
dimensional lattices.Comment: 30 pages, 5 figures now included; typos in Example 1 correcte
Suppression of core polarization in halo nuclei
We present a microscopic study of halo nuclei, starting from the Paris and
Bonn potentials and employing a two-frequency shell model approach. It is found
that the core-polarization effect is dramatically suppressed in such nuclei.
Consequently the effective interaction for halo nucleons is almost entirely
given by the bare G-matrix alone, which presently can be evaluated with a high
degree of accuracy. The experimental pairing energies between the two halo
neutrons in He and Li nuclei are satisfactorily reproduced by our
calculation. It is suggested that the fundamental nucleon-nucleon interaction
can be probed in a clearer and more direct way in halo nuclei than in ordinary
nuclei.Comment: 11 pages, RevTex, 2 postscript figures; major revisions, matches
version to appear in Phys. Rev. Letter
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