Infinitely-fast diffusion in Single-File Systems

We have used Dynamic Monte Carlo (DMC) methods and analytical techniques to analyze Single-File Systems for which diffusion is infinitely-fast. We have simplified the Master Equation removing the fast reactions and we have introduced a DMC algorithm for infinitely-fast diffusion. The DMC method for fast diffusion give similar results as the standard DMC with high diffusion rates. We have investigated the influence of characteristic parameters, such as pipe length, adsorption, desorption and conversion rate constants on the steady-state properties of Single-File Systems with a reaction, looking at cases when all the sites are reactive and when only some of them are reactive. We find that the effect of fast diffusion on single-file properties of the system is absent even when diffusion is infinitely-fast. Diffusion is not important in these systems. Smaller systems are less reactive and the occupancy profiles for infinitely-long systems show an exponential behavior.Comment: 8 pages, 5 figure

{\eta} and {\eta}' mesons from Nf=2+1+1 twisted mass lattice QCD

We determine mass and mixing angles of eta and eta' states using Nf=2+1+1 Wilson twisted mass lattice QCD. We describe how those flavour singlet states need to be treated in this lattice formulation. Results are presented for three values of the lattice spacing, a=0.061 fm, a=0.078 fm and a=0.086 fm, with light quark masses corresponding to values of the charged pion mass in a range of 230 to 500 MeV and fixed bare strange and charm quark mass values. We obtain 557(15)(45) MeV for the eta mass (first error statistical, second systematic) and 44(5) degrees for the mixing angle in the quark flavour basis, corresponding to -10(5) degrees in the octet-singlet basis.Comment: 28 pages, 9 figures, version to appear in JHEP, extended discussion of autocorrelation times and comparison to results available in the literature, added a comment for FS-effects and clarified the description of our blocking procedur

Individual differences in metabolomics: individualised responses and between-metabolite relationships

Many metabolomics studies aim to find ‘biomarkers’: sets of molecules that are consistently elevated or decreased upon experimental manipulation. Biological effects, however, often manifest themselves along a continuum of individual differences between the biological replicates in the experiment. Such differences are overlooked or even diminished by methods in standard use for metabolomics, although they may contain a wealth of information on the experiment. Properly understanding individual differences is crucial for generating knowledge in fields like personalised medicine, evolution and ecology. We propose to use simultaneous component analysis with individual differences constraints (SCA-IND), a data analysis method from psychology that focuses on these differences. This method constructs axes along the natural biochemical differences between biological replicates, comparable to principal components. The model may shed light on changes in the individual differences between experimental groups, but also on whether these differences correspond to, e.g., responders and non-responders or to distinct chemotypes. Moreover, SCA-IND reveals the individuals that respond most to a manipulation and are best suited for further experimentation. The method is illustrated by the analysis of individual differences in the metabolic response of cabbage plants to herbivory. The model reveals individual differences in the response to shoot herbivory, where two ‘response chemotypes’ may be identified. In the response to root herbivory the model shows that individual plants differ strongly in response dynamics. Thereby SCA-IND provides a hitherto unavailable view on the chemical diversity of the induced plant response, that greatly increases understanding of the system

Case management in primary palliative care is associated more strongly with organisational than with patient characteristics: results from a cross-sectional prospective study

Background: Case managers have been introduced in Dutch primary palliative care; these are nurses with expertise in palliative care who offer support to patients and informal carers in addition to the care provided by the general practitioner and home care nurses. This study aims to describe support and investigate what characteristics of patients and the organizational setting are related to the number of contacts and to the number of times topics are discussed between the case manager and patients and/or informal carers. Methods: Prospective study following cancer patients (n = 662) receiving support from a palliative care case manager in Dutch primary care, using registration forms filled out by the case manager after contact with the patient and/or informal carer. In backward linear regression, the association was studied between patient or organizational characteristics and the number of contacts and the number of times conversation topics were discussed. Results: Organizational characteristics add more to explained variability in data than patient characteristics. Case managers provide support in a flexible manner with regard to the number, mode, persons present, and duration of contacts. Support covered all domains of palliative care, with most attention given to physical complaints, life expectancy and psychological aspects. Conclusions: Support offered by the case managers is prompted by characteristics of the organization for which they work. This is contradictory to the idea of patient centered care highly valued in palliative care

Statistical validation of megavariate effects in ASCA

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

High serum alkaline phosphatase levels, a study in 181 Thai adult hospitalized patients

BACKGROUND: Alkaline phosphatase (ALP) is an important enzyme mainly derived from the liver, bones and in lesser amounts from intestines, placenta, kidneys and leukocytes. An increase in ALP levels in the serum is frequently associated with a variety of diseases. This study was done in order to determine the diseases associated with a high ALP level among Thai adult hospitalized patients. METHOD: A review was made of medical records of inpatients with high ALP level above 1000 IU/L in King Chulalongkorn Memorial Hospital, Thailand from January 1999 to December 1999. Excluded were cases of (a) patients who have bone involvements with malignancies, (b) pediatric patients younger than 15 years old and c) HIV-seropositive patients. RESULTS: A total of 181 hospitalized patients with eligible medical records were identified (96 males and 85 females, mean age 49.4 ± 16.1 years). Their ALP levels ranging from 1,001 to 3,067 IU/L, these patients were divided into four groups. CONCLUSION: High serum ALP levels in hospitalized patients were commonly found in three major groups having obstructive biliary diseases, infiltrative liver disease and sepsis. The study results were in accordance with previous reports in developed countries. Nonetheless, cholangiocarcionoma and some tropical diseases unique to our setting were also detected in these cases. where there was a marked elevation of serum ALP

Between Metabolite Relationships: an essential aspect of metabolic change

Not only the levels of individual metabolites, but also the relations between the levels of different metabolites may indicate (experimentally induced) changes in a biological system. Component analysis methods in current ‘standard’ use for metabolomics, such as Principal Component Analysis (PCA), do not focus on changes in these relations. We therefore propose the concept of ‘Between Metabolite Relationships’ (BMRs): common changes in the covariance (or correlation) between all metabolites in an organism. Such structural changes may indicate metabolic change brought about by experimental manipulation but which are lost with standard data analysis methods. These BMRs can be analysed by the INdividual Differences SCALing (INDSCAL) method. First the BMR quantification is described and subsequently the INDSCAL method. Finally, two studies illustrate the power and the applicability of BMRs in metabolomics. The first study is about the induced plant response of cabbage to herbivory, of which BMRs are a considerable part. In the second study—a human nutritional intervention study of green tea extract—standard data analysis tools did not reveal any metabolic change, although the BMRs were considerably affected. The presented results show that BMRs can be easily implemented in a wide variety of metabolomic studies. They provide a new source of information to describe biological systems in a way that fits flawlessly into the next generation of systems biology questions, dealing with personalized responses

Impact of agglomeration state of nano- and submicron sized gold particles on pulmonary inflammation

BACKGROUND: Nanoparticle (NP) toxicity testing comes with many challenges. Characterization of the test substance is of crucial importance and in the case of NPs, agglomeration/aggregation state in physiological media needs to be considered. In this study, we have addressed the effect of agglomerated versus single particle suspensions of nano- and submicron sized gold on the inflammatory response in the lung. Rats were exposed to a single dose of 1.6 mg/kg body weight (bw) of spherical gold particles with geometric diameters of 50 nm or 250 nm diluted either by ultrapure water or by adding phosphate buffered saline (PBS). A single dose of 1.6 mg/kg bw DQ12 quartz was used as a positive control for pulmonary inflammation. Extensive characterization of the particle suspensions has been performed by determining the zetapotential, pH, gold concentration and particle size distribution. Primary particle size and particle purity has been verified using transmission electron microscopy (TEM) techniques. Pulmonary inflammation (total cell number, differential cell count and pro-inflammatory cytokines), cell damage (total protein and albumin) and cytotoxicity (alkaline phosphatase and lactate dehydrogenase) were determined in bronchoalveolar lavage fluid (BALF) and acute systemic effects in blood (total cell number, differential cell counts, fibrinogen and C-reactive protein) 3 and 24 hours post exposure. Uptake of gold particles in alveolar macrophages has been determined by TEM. RESULTS: Particles diluted in ultrapure water are well dispersed, while agglomerates are formed when diluting in PBS. The particle size of the 50 nm particles was confirmed, while the 250 nm particles appear to be 200 nm using tracking analysis and 210 nm using TEM. No major differences in pulmonary and systemic toxicity markers were observed after instillation of agglomerated versus single gold particles of different sizes. Both agglomerated as well as single nanoparticles were taken up by macrophages. CONCLUSION: Primary particle size, gold concentration and particle purity are important features to check, since these characteristics may deviate from the manufacturer's description. Suspensions of well dispersed 50 nm and 250 nm particles as well as their agglomerates produced very mild pulmonary inflammation at the same mass based dose. We conclude that single 50 nm gold particles do not pose a greater acute hazard than their agglomerates or slightly larger gold particles when using pulmonary inflammation as a marker for toxicity

Expression quantitative trait loci are highly sensitive to cellular differentiation state

Blood cell development from multipotent hematopoietic stem cells to specialized blood cells is accompanied by drastic changes in gene expression for which the triggers remain mostly unknown. Genetical genomics is an approach linking natural genetic variation to gene expression variation, thereby allowing the identification of genomic loci containing gene expression modulators (eQTLs). In this paper, we used a genetical genomics approach to analyze gene expression across four developmentally close blood cell types collected from a large number of genetically different but related mouse strains. We found that, while a significant number of eQTLs (365) had a consistent “static” regulatory effect on gene expression, an even larger number were found to be very sensitive to cell stage. As many as 1,283 eQTLs exhibited a “dynamic” behavior across cell types. By looking more closely at these dynamic eQTLs, we show that the sensitivity of eQTLs to cell stage is largely associated with gene expression changes in target genes. These results stress the importance of studying gene expression variation in well-defined cell populations. Only such studies will be able to reveal the important differences in gene regulation between different ce