Computing the shortest elementary flux modes in genome-scale metabolic networks

This article is available open access through the publisher’s website through the link below. Copyright @ The Author 2009.Motivation: Elementary flux modes (EFMs) represent a key concept to analyze metabolic networks from a pathway-oriented perspective. In spite of considerable work in this field, the computation of the full set of elementary flux modes in large-scale metabolic networks still constitutes a challenging issue due to its underlying combinatorial complexity. Results: In this article, we illustrate that the full set of EFMs can be enumerated in increasing order of number of reactions via integer linear programming. In this light, we present a novel procedure to efficiently determine the K-shortest EFMs in large-scale metabolic networks. Our method was applied to find the K-shortest EFMs that produce lysine in the genome-scale metabolic networks of Escherichia coli and Corynebacterium glutamicum. A detailed analysis of the biological significance of the K-shortest EFMs was conducted, finding that glucose catabolism, ammonium assimilation, lysine anabolism and cofactor balancing were correctly predicted. The work presented here represents an important step forward in the analysis and computation of EFMs for large-scale metabolic networks, where traditional methods fail for networks of even moderate size. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online (http://bioinformatics.oxfordjournals.org/cgi/content/full/btp564/DC1).Fundação Calouste Gulbenkian, Fundação para a Ciência e a Tecnologia (FCT) and Siemens SA Portugal

Serological surveillance reveals patterns of exposure to H5 and H7 influenza A viruses in European poultry

Influenza A viruses of H5 and H7 subtype in poultry can circulate subclinically, and subsequently mutate from low to high pathogenicity with potentially devastating economic and welfare consequences. European Union Member States undertake surveillance of commercial and backyard poultry for early detection and control of subclinical H5 and H7 influenza A infection. This surveillance has moved towards a risk‐based sampling approach in recent years; however quantitative measures of relative risk associated with risk factors utilised in this approach are necessary for optimisation. This study describes serosurveillance for H5 and H7 influenza A in domestic and commercial poultry undertaken in the European Union from 2004 to 2010, where a random sampling and thus representative approach to serosurveillance was undertaken. Using these representative data, this study measured relative risk of seropositivity across poultry categories and spatially across the EU. Data were analysed using multivariable logistic regression. Domestic waterfowl, game birds, fattening turkeys, ratites, backyard poultry and the “other” poultry category holdings had relatively increased probability of H5 and/or H7 influenza A seropositivity, compared to laying‐hen holdings. Amongst laying‐hen holdings, free‐range rearing was associated with increased probability of H7 seropositivity. Spatial analyses detected ‘hotspots’ for H5 influenza A seropositivity in western France and England, and H7 influenza A seropositivity in Italy and Belgium, which may be explained by the demographics and distribution of poultry categories. Findings suggest certain poultry category holdings are at increased risk of subclinical H5 and/or H7 influenza A circulation, and free‐range rearing increases the likelihood of exposure to H7 influenza A. These findings may be used in further refining risk‐based surveillance strategies, and prioritising management strategies in influenza A outbreaks

Structure and photophysics of indigoids for singlet fission: Cibalackrot

We report an investigation of structure and photophysics of thin layers of cibalackrot, a sturdy dye derived from indigo by double annulation at the central double bond. Evaporated layers contain up to three phases, two crystalline and one amorphous. Relative amounts of all three have been determined by a combination of X-ray diffraction and FT-IR reflectance spectroscopy. Initially, excited singlet state rapidly produces a high yield of a transient intermediate whose spectral properties are compatible with charge-transfer nature. This intermediate more slowly converts to a significant yield of triplet, which, however, does not exceed 100% and may well be produced by intersystem crossing rather than singlet fission. The yields were determined by transient absorption spectroscopy and corrected for effects of partial sample alignment by a simple generally applicable procedure. Formation of excimers was also observed. In order to obtain guidance for improving molecular packing by a minor structural modification, calculations by a simplified frontier orbital method were used to find all local maxima of singlet fission rate as a function of geometry of a molecular pair. The method was tested at 48 maxima by comparison with the ab initio Frenkel-Davydov exciton model. Published under license by AIP Publishing

Aging Skin: Nourishing from the Inside Out, Effects of Good Versus Poor Nitrogen Intake on Skin Health and Healing

Skin is the outermost defense organ which protects us from the environment, constituting around 8 % of an adult’s body weight. Healthy skin contains one-eighth of the body’s total proteins. The balance of turnover and synthesis of skin proteins is primarily dependent on the availability of sufficient nitrogen-containing substrates, namely, amino acids, essential for protein metabolism in any other tissue and body organs. The turnover of skin proteins has been shown to be rapid, and the mobilization of amino acids at the expense of skin proteins is relevant in experimental models of protein malnutrition. As a result, alterations in nutritional status should be suspected, diagnosed, and eventually treated for any skin lesions. Protein malnutrition has a dramatic prevalence in patients aged >70 or more, independent of the reason for hospitalization. The quality of nutrition and content of essential amino acids are strictly connected to skin health and integrity of its protein components. Collagen fiber deposition is highly and rapidly influenced by alterations in the essential to nonessential amino acid ratios. The most relevant nutritional factor of skin health is the prevalence of essential amino acids

Expression of estrogen receptor beta in the breast carcinoma of BRCA1 mutation carriers

<p>Abstract</p> <p>Background</p> <p>Breast cancers (BC) in women carrying mutations in BRCA1 gene are more frequently estrogen receptor negative than the nonhereditary BC. Nevertheless, tamoxifen has been found to have a protective effect in preventing contralateral tumors in BRCA1 mutation carriers. The identification of the second human estrogen receptor, ERβ, raised a question of its role in hereditary breast cancer. The aim of this study was to assess the frequency of ERα, ERβ, PgR (progesterone receptor) and HER-2 expression in breast cancer patients with mutated <it>BRCA1 </it>gene and in the control group.</p> <p>Methods</p> <p>The study group consisted of 48 women with <it>BRCA1 </it>gene mutations confirmed by multiplex PCR assay. The patients were tested for three most common mutations of BRCA1 affecting the Polish population (5382insC, C61G, 4153delA). Immunostaining for ERα, ERβ and PgR (progesterone receptor) was performed using monoclonal antibodies against ERα, PgR (DakoCytomation), and polyclonal antibody against ERβ (Chemicon). The EnVision detection system was applied. The study population comprised a control group of 120 BC operated successively during the years 1998–99.</p> <p>Results</p> <p>The results of our investigation showed that <it>BRCA1 </it>mutation carriers were more likely to have ERα-negative breast cancer than those in the control group. Only 14.5% of <it>BRCA1</it>-related cancers were ERα-positive compared with 57.5% in the control group (<it>P </it>< 0.0001). On the contrary, the expression of ERβ protein was observed in 42% of <it>BRCA1</it>-related tumors and in 55% of the control group. An interesting finding was that most hereditary cancers (75% of the whole group) were triple-negative: ERα(-)/PgR(-)/HER-2(-) but almost half of this group (44.4%) showed the expression of ERβ.</p> <p>Conclusion</p> <p>In the case of <it>BRCA1</it>-associated tumors the expression of ERβ was significantly higher than the expression of ERα. This may explain the effectiveness of tamoxifen in preventing contralateral breast cancer development in <it>BRCA1 </it>mutation carriers.</p

EQ-5D in Central and Eastern Europe : 2000-2015

Objective: Cost per quality-adjusted life year data are required for reimbursement decisions in many Central and Eastern European (CEE) countries. EQ-5D is by far the most commonly used instrument to generate utility values in CEE. This study aims to systematically review the literature on EQ-5D from eight CEE countries. Methods: An electronic database search was performed up to July 1, 2015 to identify original EQ-5D studies from the countries of interest. We analysed the use of EQ-5D with respect to clinical areas, methodological rigor, population norms and value sets. Results: We identified 143 studies providing 152 country-specific results with a total sample size of 81,619: Austria (n=11), Bulgaria (n=6), Czech Republic (n=18), Hungary (n=47), Poland (n=51), Romania (n=2), Slovakia (n=3) and Slovenia (n=14). Cardiovascular (20%), neurologic (16%), musculoskeletal (15%) and endocrine/nutritional/metabolic diseases (14%) were the most frequently studied clinical areas. Overall 112 (78%) of the studies reported EQ VAS results and 86 (60%) EQ-5D index scores, of which 27 (31%) did not specify the applied tariff. Hungary, Poland and Slovenia have population norms. Poland and Slovenia also have a national value set. Conclusions: Increasing use of EQ-5D is observed throughout CEE. The spread of health technology assessment activities in countries seems to be reflected in the number of EQ-5D studies. However, improvement in informed use and methodological quality of reporting is needed. In jurisdictions where no national value set is available, in order to ensure comparability we recommend to apply the most frequently used UK tariff. Regional collaboration between CEE countries should be strengthened

A Public Survey on Handling Male Chicks in the Dutch Egg Sector

In 2035 global egg demand will have risen 50% from 1985. Because we are not able to tell in the egg whether it will become a male or female chick, billons of one day-old male chicks will be killed. International research initiatives are underway in this area, and governments encourage the development of an alternative with the goal of eliminating the culling of day-old male chicks. The Netherlands holds an exceptional position in the European egg trade, but is also the only country in the European Union where the downside of the egg sector, the practice of killing day-old male chicks, is a recurrent subject of societal debate. ‘Preventing the killing of young animals’ and ‘in ovo sex determination’ are the two alternative approaches available to solve this problem. It is clear that both approaches solve the problem of killing day-old male chicks, either by keeping them alive or by preventing them from living, but they also raise a lot of new animal welfare-related dilemmas. A thorough analysis was undertaken of these dilemmas and the results are presented in this article. The analysis resulted in an ethical framework based on the two main approaches in bioethics: a consequentialist approach and a deontological approach. This ethical framework was used to develop an online survey administered to ascertain Dutch public opinion about these alternative approaches. The results show that neither alternative will be fully accepted, or accepted by more than half of Dutch society. However, the survey does provide an insight into the motives that are important for people’s choice: food safety and a good treatment of animals. Irrespective of the approach chosen, these values should be safeguarded and communicated clearly

Performance and running experience of the Belle II silicon vertex detector

The Belle II silicon vertex detector is one of the vertex detectors in the Belle II experiment. The detector reads out the signals from the double-sided silicon strip sensors with the APV25 front-end readout ASIC, adopting the chip-on-sensor concept to minimize the strip noise. The detector has been operated in the experiment since the spring of 2019. Analyzing the acquired data during the beam collisions, the excellent performance of the detector is confirmed. Also, the radiation dose and 1-MeV equivalent neutron fluence of the detector are estimated using the measured dose rates of the diamond sensors installed on the beam pipe and are compared with the measured radiation effects in the strip noise, leakage current, and depletion voltage. This paper briefly introduces the main features of the silicon vertex detector, and then reports on the measured performance and radiation effects of the first two years of running experience of the detector

New Results from the Silicon Vertex Detector of the Belle II Experiment

The Silicon Vertex Detector (SVD) consists of four layers of double-sided silicon strip sensors. The SVD is one of the two vertex subdetectors within Belle II. Since the start of data taking in 2019 at the Super-KEKB collider (KEK, Japan), which has the highest peak-luminosity ever recorded, the SVD is operated reliably and with high efficiency, despite exposure to harsh beam background. Measurements using data show that the SVD has both high signal-to-noise ratio and hit efficiency, as well precise spatial resolution. Further these properties are stable over time. Recently the simulation has been tuned, using data, to improve the agrement between data and MC for cluster properties. The good hit-time resolution can be exploited to further improve the robustness against the higher levels of background expected as the instantaneous luminosity increases in the next years of running. First effects of radiation damage on strip noise, sensor currents and depletion voltage have been measured, although they do not have any detrimental effect on the performance of the detector