Comment on "Deficiencies in molecular dynamics simulation-based prediction of protein-DNA binding free energy landscapes"

Sequence-specific DNA binding transcription factors play an essential role in the transcriptional regulation of all organisms. The development of reliable in silico methods to predict the binding affinity landscapes of transcription factors thus promises to provide rapid screening of transcription factor specificities and, at the same time, yield valuable insight into the atomistic details of the interactions driving those specificities. Recent literature has reported highly discrepant results on the current ability of state-of-the-art atomistic molecular dynamics simulations to reproduce experimental binding free energy landscapes for transcription factors. Here, we resolve one important discrepancy by noting that in the case of alchemical free energy calculations involving base pair mutations, a common convention used in improving end point convergence of mixed potentials in fact can lead to erroneous results. The underlying cause for inaccurate double free energy difference estimates is specific to the particular implementation of the alchemical transformation protocol. Using the Gromacs simulation package, which is not affected by this issue, we obtain free energy landscapes in agreement with the experimental measurements; equivalent results are obtained for a small set of test cases with a modified version of the AMBER package. Our findings provide a consistent and optimistic outlook on the current state of prediction of protein-DNA binding free energy interactions using molecular dynamics simulations and an important precaution for appropriate end point handling in a broad range of free energy calculations

IoT big data value map : how to generate value from IoT data

Huge sources of business value are emerging due to big data generated by the Internet of Things (IoT) technologies paired with Machine Learning (ML) and Data Mining (DM) techniques' ability to harness and extract hidden knowledge from data and consequently learning and improving spontaneously. This paper reviews different examples of analyzing big data generated through IoT in previous studies and in various domains; then claims their business Value Proposition Map deploying Value Proposition Canvas as a novel conceptual tool. As a result, the proposed unprecedented framework of this paper entitled "IoT Big Data Value Map" shows a roadmap from raw data to real-world business value creation, blossomed out of a kind of three-pillar structure: IoT, Data Mining, and Value Proposition Map. The result of this study paves the way for prototyping business models in this field based on value invention from huge data analysis generated by IoT devices in different industries. Furthermore, researchers may complete this map by associating proposed framework with potential customers' profile and their expectations

A study of affecting factors on the degree of university students loyalty to the brand of nike

There are different factors which affect the way people select and continue their attitudes towards products of certain brands. The main objective of the present study was investigating factors affecting the degree of University students’ loyalty  to Nike brand. This research is functional in regard with objective and descriptive-temporary in terms of kind; it was conducted among BA, MA, and PhD student of Physical Education in Tehran University with a sample size of 248 subjects. Researcher-constructed questionnaire, which examined three influential factors (trust, purchase intent, brand image), on the loyalty of University Students, was used to collect data. Research data was analyzed using EM algorithm and Spss software and stepwise multiple regression was applied to investigate the impact of variables on students’ loyalty. Significant regression model showed that all three variables of trust, purchase intent, and brand image had significant effects. Brand trust was the most influential variable with regression coefficient of   0.740 (p<0.001).Based on the results of the present study, the hierarchical priority of three variables, according to students’ replies, was brand trust, purchase intent, and brand image. The results showed that brand trust had the first priority among variables and that Nike brand has managed, on the basis of quality, to satisfy various needs, intentions, and tasks of larger number of university students.Key words: Nike brand, brand trusts, brand image, loyalty, purchase inten

Preventive maintenance of flexible pavement and mechanical properties of steel slag asphalt

Preventive maintenance is beneficial if pavement life is increased while maintaining its service ability, and it is an environmental problem. Steel slag material is inorganic, it can neither be incinerated nor decomposed, so it may be difficult to reclaim. This work aims to study the performance of asphalt concrete where some of the fractional fine aggregate is replaced with crushed steel slag material. Steel slag materials are brittle and rich in carbon and silicon, so the key technical indexes of steel slag‐asphalt concrete are strength. Materials used in the tests included AC 60–70 bitumen, limestone aggregate and crushed recycled steel slag. The Marshall test was used to examine the influence of optimal asphalt content, volume properties and strength of asphalt concrete when different percentages of crushed steel slag were added. The high‐temperature stability and creep stiffness performance of steel slag asphalt concrete was also tested, and the results are satisfactory. The investigation has demonstrated that the recycling and use of waste steel slag in asphalt concrete is feasible. Santrauka Profilaktinis remontas yra naudingas, jei kelio dangos patvarumas didinamas išlaikant teikiamas paslaugas, kartu tai svarbi aplinkos problema. Plieno šlakas yra neorganinės kilmės ir negali būti nei deginamas, nei skaidomas, todėl sunkiai utilizuojamas. Šiame darbe stengtasi įvertinti asfalto betono charakteristiką, kai dalis smulkios frakcijos yra pakeista susmulkintu plieno šlaku. Ši medžiaga trapi, joje daug anglies ir silikono, todėl vienas pagrindinių techninių plieno šlako rodiklių yra stiprumas. Tyrimams buvo naudotas AC 60–70 bitumas, klinčių užpildas ir susmulkintas perdirbtas plieno šlakas. Maršalo tyrimas taikytas siekiant įvertinti optimalų asfalto kiekį, asfalto betono tūrines savybes ir stiprumą esant skirtingai susmulkinto plieno šlako procentinei daliai. Tyrimo rezultatai parodė pakankamą plieno šlako asfalto betono stabilumą esant aukštai temperatūrai ir šlyties standumą. Tyrimo rezultatai parodė, kad plieno šlakas gali būti perdirbamas ir panaudojamas asfalto betone kaip sudėtinė dalis. Reikšminiai žodžiai: plieno šlakas, asfalto betonas, standumas šlyčiai, atliekos, profilaktinis remontas, perdirbimas. Профилактический ремонт дорожного покрытия и механические свойства асфальта со стальным шлаком Резюме Профилактический ремонт полезен, если долговечность дорожного покрытия увеличивается при сохранении оказываемых услуг, а также в отношении охраны окружающей среды. Стальной шлак не является органическим веществом, поэтому его нельзя сжечь либо как-то утилизировать. Нами была предпринята попытка оценить характеристику асфальтобетона, мелкая фракция которого частично заменена дробленым стальным шлаком. Этот материал хрупок, в нем много угля и силикона, поэтому одним из основных технических показателей стального шлака является прочность. Исследованиям подвергался битум АС 60–70, известковый заполнитель и дробленый переработанный стальной шлак. Для определения оптимального количества асфальта, свойств и прочности асфальтобетона при разном процентном составе дробленого стального шлака применялся метод Маршалла. Исследования подтвердили достаточную стабильность асфальтобетона со стальным шлаком при высокой температуре, сдвиговую жесткость, а также возможность переработки стального шлака и применения его в качестве составной части асфальтобетона. Ключевые слова: стальной шлак, асфальтобетон, сдвиговая жесткость, отходы, профилактический ремонт, переработка. First Published Online: 14 Oct 201

Locating stations of public transportation vehicles for improving transit accessibility

Since transportation is one of the most complicated and the basic problem of urban life in developing countries at the present time and in various dimensions, so it is necessary to view it more scientifically‐ practically. Reducing travelling time is one way to reduce its cost .In public transportation system, it is important to determine proper travelling costs. There are various methods to determine the distances between stations. One of these methods used in England is based on logical and calculative relations in mathematics. In this paper, in addition to studying this method some changes have been made in order to reduce and modify required variables for calculation of those relations. A numerical example is designed to demonstrate the effectiveness of the method and thus developed to optimize the public transportation stop location problem. The sensitivity of the total travel time, access, speed and the effect of the parameters on the optimum stop location are analyzed and discussed. First Published Online: 27 Oct 201

Translation and validation of the German version of the Mother-Generated Index and its application during the postnatal period.

the Mother-Generated Index (MGI) is a validated tool to assess postnatal quality of life. It is usually administered several weeks or months after birth and correlates with indices of post partum mood states and physical complaints. The instrument had not been translated into German before or validated for use among German-speaking women, nor have the results of the tool been assessed specifically for the administration directly after birth. This paper aims to describe the systematic translation process of the MGI into German and to assess the convergent validity of the German version of the instrument directly after birth and seven weeks post partum

Yttrium-90 microsphere induced gastrointestinal tract ulceration

© 2008 South et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Cultural differences in postnatal quality of life among German-speaking women - a prospective survey in two countries.

Assessment of quality of life after childbirth is an important health-outcome measurement for new mothers and is of special interest in midwifery. The Mother-Generated Index (MGI) is a validated instrument to assess postnatal quality of life. The tool has not been applied for making a cross-cultural comparison before. This study investigated (a) responses to the MGI in German-speaking women in Germany and Switzerland; and (b) associations between MGI scores on the one hand and maternity and midwifery care on the other

Past, present, and future of global health financing: a review of development assistance, government, out-of-pocket, and other private spending on health for 195 countries, 1995–2050

Background: Comprehensive and comparable estimates of health spending in each country are a key input for health policy and planning, and are necessary to support the achievement of national and international health goals. Previous studies have tracked past and projected future health spending until 2040 and shown that, with economic development, countries tend to spend more on health per capita, with a decreasing share of spending from development assistance and out-of-pocket sources. We aimed to characterise the past, present, and predicted future of global health spending, with an emphasis on equity in spending across countries. Methods: We estimated domestic health spending for 195 countries and territories from 1995 to 2016, split into three categories—government, out-of-pocket, and prepaid private health spending—and estimated development assistance for health (DAH) from 1990 to 2018. We estimated future scenarios of health spending using an ensemble of linear mixed-effects models with time series specifications to project domestic health spending from 2017 through 2050 and DAH from 2019 through 2050. Data were extracted from a broad set of sources tracking health spending and revenue, and were standardised and converted to inflation-adjusted 2018 US dollars. Incomplete or low-quality data were modelled and uncertainty was estimated, leading to a complete data series of total, government, prepaid private, and out-of-pocket health spending, and DAH. Estimates are reported in 2018 US dollars, 2018 purchasing-power parity-adjusted dollars, and as a percentage of gross domestic product. We used demographic decomposition methods to assess a set of factors associated with changes in government health spending between 1995 and 2016 and to examine evidence to support the theory of the health financing transition. We projected two alternative future scenarios based on higher government health spending to assess the potential ability of governments to generate more resources for health. Findings: Between 1995 and 2016, health spending grew at a rate of 4·00% (95% uncertainty interval 3·89–4·12) annually, although it grew slower in per capita terms (2·72% [2·61–2·84]) and increased by less than $1 per capita over this period in 22 of 195 countries. The highest annual growth rates in per capita health spending were observed in upper-middle-income countries (5·55 in lower-middle-income countries (3·71$8·0 trillion (7·8–8·1) in 2016 (comprising 8·6% [8·4–8·7] of the global economy and $10·3 trillion [10·1–10·6] in purchasing-power parity-adjusted dollars), with a per capita spending of US$5252 (5184–5319) in high-income countries, $491 (461–524) in upper-middle-income countries,$81 (74–89) in lower-middle-income countries, and $40 (38–43) in low-income countries. In 2016, 0·4 countries, despite these countries comprising 10·0 DAH targeted HIV/AIDS ($9·5 billion, 24·3% of total DAH), although spending on other infectious diseases (excluding tuberculosis and malaria) grew fastest from 2010 to 2018 (6·27% per year). The leading sources of DAH were the USA and private philanthropy (excluding corporate donations and the Bill & Melinda Gates Foundation). For the first time, we included estimates of China’s contribution to DAH ($644·7 million in 2018). Globally, health spending is projected to increase to$15·0 trillion (14·0–16·0) by 2050 (reaching 9·4% [7·6–11·3] of the global economy and $21·3 trillion [19·8–23·1] in purchasing-power parity-adjusted dollars), but at a lower growth rate of 1·84% (1·68–2·02) annually, and with continuing disparities in spending between countries. In 2050, we estimate that 0·6% (0·6–0·7) of health spending will occur in currently low-income countries, despite these countries comprising an estimated 15·7% of the global population by 2050. The ratio between per capita health spending in high-income and low-income countries was 130·2 (122·9–136·9) in 2016 and is projected to remain at similar levels in 2050 (125·9 [113·7–138·1]). The decomposition analysis identified governments’ increased prioritisation of the health sector and economic development as the strongest factors associated with increases in government health spending globally. Future government health spending scenarios suggest that, with greater prioritisation of the health sector and increased government spending, health spending per capita could more than double, with greater impacts in countries that currently have the lowest levels of government health spending Interpretation: Financing for global health has increased steadily over the past two decades and is projected to continue increasing in the future, although at a slower pace of growth and with persistent disparities in per-capita health spending between countries. Out-of-pocket spending is projected to remain substantial outside of high-income countries. Many low-income countries are expected to remain dependent on development assistance, although with greater government spending, larger investments in health are feasible. In the absence of sustained new investments in health, increasing efficiency in health spending is essential to meet global health targets. Funding: Bill & Melinda Gates Foundatio

Past, present, and future of global health financing : a review of development assistance, government, out-of-pocket, and other private spending on health for 195 countries, 1995-2050

Background Comprehensive and comparable estimates of health spending in each country are a key input for health policy and planning, and are necessary to support the achievement of national and international health goals. Previous studies have tracked past and projected future health spending until 2040 and shown that, with economic development, countries tend to spend more on health per capita, with a decreasing share of spending from development assistance and out-of-pocket sources. We aimed to characterise the past, present, and predicted future of global health spending, with an emphasis on equity in spending across countries. Methods We estimated domestic health spending for 195 countries and territories from 1995 to 2016, split into three categories-government, out-of-pocket, and prepaid private health spending-and estimated development assistance for health (DAH) from 1990 to 2018. We estimated future scenarios of health spending using an ensemble of linear mixed-effects models with time series specifications to project domestic health spending from 2017 through 2050 and DAH from 2019 through 2050. Data were extracted from a broad set of sources tracking health spending and revenue, and were standardised and converted to inflation-adjusted 2018 US dollars. Incomplete or low-quality data were modelled and uncertainty was estimated, leading to a complete data series of total, government, prepaid private, and out-of-pocket health spending, and DAH. Estimates are reported in 2018 US dollars, 2018 purchasing-power parity-adjusted dollars, and as a percentage of gross domestic product. We used demographic decomposition methods to assess a set of factors associated with changes in government health spending between 1995 and 2016 and to examine evidence to support the theory of the health financing transition. We projected two alternative future scenarios based on higher government health spending to assess the potential ability of governments to generate more resources for health. Findings Between 1995 and 2016, health spending grew at a rate of 4.00% (95% uncertainty interval 3.89-4.12) annually, although it grew slower in per capita terms (2.72% [2.61-2.84]) and increased by less than $1 per capita over this period in 22 of 195 countries. The highest annual growth rates in per capita health spending were observed in upper-middle-income countries (5.55$ 8.0 trillion (7.8-8.1) in 2016 (comprising 8.6% [8.4-8.7] of the global economy and $10.3 trillion [10.1-10.6] in purchasing-power parity-adjusted dollars), with a per capita spending of US$ 5252 (5184-5319) in high-income countries, $491 (461-524) in upper-middle-income countries,$ 81 (74-89) in lower-middle-income countries, and $40 (38-43) in low-income countries. In 2016, 0.4$ 9.5 billion, 24.3% of total DAH), although spending on other infectious diseases (excluding tuberculosis and malaria) grew fastest from 2010 to 2018 (6.27% per year). The leading sources of DAH were the USA and private philanthropy (excluding corporate donations and the Bill & Melinda Gates Foundation). For the first time, we included estimates of China's contribution to DAH ($644.7 million in 2018). Globally, health spending is projected to increase to$ 15.0 trillion (14.0-16.0) by 2050 (reaching 9.4% [7.6-11.3] of the global economy and $ 21.3 trillion [19.8-23.1] in purchasing-power parity-adjusted dollars), but at a lower growth rate of 1.84% (1.68-2.02) annually, and with continuing disparities in spending between countries. In 2050, we estimate that 0.6% (0.6-0.7) of health spending will occur in currently low-income countries, despite these countries comprising an estimated 15.7% of the global population by 2050. The ratio between per capita health spending in high-income and low-income countries was 130.2 (122.9-136.9) in 2016 and is projected to remain at similar levels in 2050 (125.9 [113.7-138.1]). The decomposition analysis identified governments' increased prioritisation of the health sector and economic development as the strongest factors associated with increases in government health spending globally. Future government health spending scenarios suggest that, with greater prioritisation of the health sector and increased government spending, health spending per capita could more than double, with greater impacts in countries that currently have the lowest levels of government health spending. Interpretation Financing for global health has increased steadily over the past two decades and is projected to continue increasing in the future, although at a slower pace of growth and with persistent disparities in per-capita health spending between countries. Out-of-pocket spending is projected to remain substantial outside of high-income countries. Many low-income countries are expected to remain dependent on development assistance, although with greater government spending, larger investments in health are feasible. In the absence of sustained new investments in health, increasing efficiency in health spending is essential to meet global health targets.Peer reviewe