A statistical mechanics description of environmental variability in metabolic networks

Many of the chemical reactions that take place within a living cell are irreversible. Due to evolutionary pressures, the number of allowable reactions within these systems are highly constrained and thus the resulting metabolic networks display considerable asymmetry. In this paper, we explore possible evolutionary factors pertaining to the reduced symmetry observed in these networks, and demonstrate the important role environmental variability plays in shaping their structural organization. Interpreting the returnability index as an equilibrium constant for a reaction network in equilibrium with a hypothetical reference system, enables us to quantify the extent to which a metabolic network is in disequilibrium. Further, by introducing a new directed centrality measure via an extension of the subgraph centrality metric to directed networks, we are able to characterise individual metabolites by their participation within metabolic pathways. To demonstrate these ideas, we study 116 metabolic networks of bacteria. In particular, we find that the equilibrium constant for the metabolic networks decreases significantly in-line with variability in bacterial habitats, supporting the view that environmental variability promotes disequilibrium within these biochemical reaction system

Photosystem II Peripheral Accessory Chlorophyll Mutants in Chlamydomonas reinhardtii. Biochemical Characterization and Sensitivity to Photo-Inhibition

In addition to the four chlorophylls (Chls) involved in primary charge separation, the photosystem II (PSII) reaction center polypeptides, D1 and D2, coordinate a pair of symmetry-related, peripheral accessory Chls. These Chls are axially coordinated by the D1-H118 and D2-H117 residues and are in close association with the proximal Chl antennae proteins, CP43 and CP47. To gain insight into the function(s) of each of the peripheral Chls, we generated site-specific mutations of the amino acid residues that coordinate these Chls and characterized their energy and electron transfer properties. Our results demonstrate that D1-H118 and D2-H117 mutants differ with respect to: (a) their relative numbers of functional PSII complexes, (b) their relative ability to stabilize charge-separated states, (c) light-harvesting efficiency, and (d) their sensitivity to photo-inhibition. The D2-H117N and D2-H117Q mutants had reduced levels of functional PSII complexes and oxygen evolution capacity as well as reduced light-harvesting efficiencies relative to wild-type cells. In contrast, the D1-H118Q mutant was capable of near wild-type rates of oxygen evolution at saturating light intensities. The D1-H118Q mutant also was substantially more resistant to photo-inhibition than wild type. This reduced sensitivity to photo-inhibition is presumably associated with a reduced light-harvesting efficiency in this mutant. Finally, it is noted that the PSII peripheral accessory Chls have similarities to a to a pair of Chls also present in the PSI reaction center complex

"Author! Author!" : Shakespeare and biography

Original article can be found at: http://www.informaworld.com/smpp/title~content=t714579626~db=all Copyright Informa / Taylor & Francis Group. DOI: 10.1080/17450910902764454Since 1996, not a year has passed without the publication of at least one Shakespeare biography. Yet for many years the place of the author in the practice of understanding literary works has been problematized, and even on occasions eliminated. Criticism reads the “works”, and may or may not refer to an author whose “life” contributed to their meaning. Biography seeks the author in the works, the personality that precedes the works and gives them their characteristic shape and meaning. But the form of literary biography addresses the unusual kind of “life” that puts itself into “works”, and this is particularly challenging where the “works” predominate massively over the salient facts of the “life”. This essay surveys the current terrain of Shakespeare biography, and considers the key questions raised by the medium: can we know anything of Shakespeare's “personality” from the facts of his life and the survival of his works? What is the status of the kind of speculation that inevitably plays a part in biographical reconstruction? Are biographers in the end telling us as much about themselves as they tell us about Shakespeare?Peer reviewe

Application of phage display to high throughput antibody generation and characterization.

We have created a high quality phage display library containing over 1010 human antibodies and describe its use in the generation of antibodies on an unprecedented scale. We have selected, screened and sequenced over 38,000 recombinant antibodies to 292 antigens, yielding over 7,200 unique clones. 4,400 antibodies were characterized by specificity testing and detailed sequence analysis and the data/clones are available online. Sensitive detection was demonstrated in a bead based flow cytometry assay. Furthermore, positive staining by immunohistochemistry on tissue microarrays was found for 37% (143/381) of antibodies. Thus, we have demonstrated the potential of and illuminated the issues associated with genome-wide monoclonal antibody generation.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

A blind detection of a large, complex, Sunyaev--Zel'dovich structure

We present an interesting Sunyaev-Zel'dovich (SZ) detection in the first of the Arcminute Microkelvin Imager (AMI) 'blind', degree-square fields to have been observed down to our target sensitivity of 100{\mu}Jy/beam. In follow-up deep pointed observations the SZ effect is detected with a maximum peak decrement greater than 8 \times the thermal noise. No corresponding emission is visible in the ROSAT all-sky X-ray survey and no cluster is evident in the Palomar all-sky optical survey. Compared with existing SZ images of distant clusters, the extent is large (\approx 10') and complex; our analysis favours a model containing two clusters rather than a single cluster. Our Bayesian analysis is currently limited to modelling each cluster with an ellipsoidal or spherical beta-model, which do not do justice to this decrement. Fitting an ellipsoid to the deeper candidate we find the following. (a) Assuming that the Evrard et al. (2002) approximation to Press & Schechter (1974) correctly gives the number density of clusters as a function of mass and redshift, then, in the search area, the formal Bayesian probability ratio of the AMI detection of this cluster is 7.9 \times 10^4:1; alternatively assuming Jenkins et al. (2001) as the true prior, the formal Bayesian probability ratio of detection is 2.1 \times 10^5:1. (b) The cluster mass is MT,200 = 5.5+1.2\times 10^14h-1M\odot. (c) Abandoning a physical model with num- -1.3 70 ber density prior and instead simply modelling the SZ decrement using a phenomenological {\beta}-model of temperature decrement as a function of angular distance, we find a central SZ temperature decrement of -295+36 {\mu}K - this allows for CMB primary anisotropies, receiver -15 noise and radio sources. We are unsure if the cluster system we observe is a merging system or two separate clusters.Comment: accepted MNRAS. 12 pages, 9 figure

Reducing errors in health care: cost-effectiveness of multidisciplinary team training in obstetric emergencies (TOSTI study); a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>There are many avoidable deaths in hospitals because the care team is not well attuned. Training in emergency situations is generally followed on an individual basis. In practice, however, hospital patients are treated by a team composed of various disciplines. To prevent communication errors, it is important to focus the training on the team as a whole, rather than on the individual. Team training appears to be important in contributing toward preventing these errors. Obstetrics lends itself to multidisciplinary team training. It is a field in which nurses, midwives, obstetricians and paediatricians work together and where decisions must be made and actions must be carried out under extreme time pressure.</p> <p>It is attractive to belief that multidisciplinary team training will reduce the number of errors in obstetrics. The other side of the medal is that many hospitals are buying expensive patient simulators without proper evaluation of the training method. In the Netherlands many hospitals have 1,000 or less annual deliveries. In our small country it might therefore be more cost-effective to train obstetric teams in medical simulation centres with well trained personnel, high fidelity patient simulators, and well defined training programmes.</p> <p>Methods/design</p> <p>The aim of the present study is to evaluate the cost-effectiveness of multidisciplinary team training in a medical simulation centre in the Netherlands to reduce the number of medical errors in obstetric emergency situations. We plan a multicentre randomised study with the centre as unit of analysis. Obstetric departments will be randomly assigned to receive multidisciplinary team training in a medical simulation centre or to a control arm without any team training.</p> <p>The composite measure of poor perinatal and maternal outcome in the non training group was thought to be 15%, on the basis of data obtained from the National Dutch Perinatal Registry and the guidelines of the Dutch Society of Obstetrics and Gynaecology (NVOG). We anticipated that multidisciplinary team training would reduce this risk to 5%. A sample size of 24 centres with a cluster size of each at least 200 deliveries, each 12 centres per group, was needed for 80% power and a 5% type 1 error probability (two-sided). We assumed an Intraclass Correlation Coefficient (ICC) value of maximum 0.08.</p> <p>The analysis will be performed according to the intention-to-treat principle and stratified for teaching or non-teaching hospitals.</p> <p>Primary outcome is the number of obstetric complications throughout the first year period after the intervention. If multidisciplinary team training appears to be effective a cost-effective analysis will be performed.</p> <p>Discussion</p> <p>If multidisciplinary team training appears to be cost-effective, this training should be implemented in extra training for gynaecologists.</p> <p>Trial Registration</p> <p>The protocol is registered in the clinical trial register number NTR1859</p

Socio-demographic determinants of coinfections by HIV, hepatitis B and hepatitis C viruses in central Italian prisoners

BACKGROUND: The coinfections HIV/HCV/HBV are an important health issue in penitentiary communities. The aim of the study was to examine HIV, HBV and HCV coinfections determinants amongst prisoners in the jails of Southern Lazio (Central Italy), in the period 1995-2000. METHODS: Diagnosis of seropositivities for HIV, HBV and HCV was made using ELISA method. A multiple logistic regression analysis was conducted to verify the influence of socio-demographic factors on the HIV/HBV/HCV coinfections. RESULTS: HIV/HCV, HBV/HCV and HIV/HBV coinfections were detected in 42 (4%), 203 (17.9%) and 31 (2.9%) inmates, respectively. These coinfections are significantly associated with the status of drug addiction (OR = 16.02; p = 0.012; OR = 4.15; p &lt; 0.001; OR = 23.57; p = 0.002), smoking habits (OR = 3.73; p = 0.033; OR = 1.42; p = 0.088; OR = 4.25; p = 0.053) and Italian nationality (OR = 7.05; p = 0.009; OR = 2.31; p &lt; 0.001; OR = 4.61; p = 0.04). CONCLUSION: The prevalence of HIV, HBV and HCV seropositivity in jails suggests that information and education programs for inmates could be useful to reduce the spread of such infections

Risk factors for hepatitis C virus infection among blood donors in southern Brazil: a case-control study

BACKGROUND: In Brazil, it is estimated that between 2.5 and 4.9% of the general population present anti-hepatitis C virus (HCV) antibodies, which corresponds to as many as 3.9 to 7.6 million chronic carriers. Chronic liver disease is associated with HCV infection in 20% to 58% of the Brazilian patients. The objective of this case-control study was to investigate the risk factors for presence of anti-HCV antibody in blood donors in southern Brazil. METHODS: One hundred and seventy eight blood donors with two positive ELISA results for anti-HCV were cases, and 356 controls tested negative. A standardized questionnaire was used to collect data concerning demographic and socioeconomic aspects, history of previous hepatitis infection, social and sexual behaviors, and number of donations. Variables were grouped into sets of hierarchical categories. Cases and controls were compared using logistic regression, odds ratios, and 95% confidence intervals. The statistical significance of the associations was assessed through likelihood ratio tests based on a P value < 0.05. RESULTS: The prevalence of anti-HCV among blood donors was 1.1%. Most of the donors were white and males. In the multivariate analysis, independent predictors of anti-HCV positivity were: intravenous drug use, blood transfusion >10 years earlier, having had two to four sexually transmitted diseases, incarceration, tattooing, sex with a hepatitis B or C virus carrier or with intravenous drug users. CONCLUSION: Intravenous drug use, blood transfusion, and tattooing were the main risk factors for anti-HCV positivity among blood donors from southern Brazil, but sexual HCV transmission should also be considered