45 research outputs found

    Study of water ingress into foamed concrete

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    Master'sMASTER OF ENGINEERIN

    Vitamin B₁₂ and folate decrease inflammation and fibrosis in NASH by preventing syntaxin 17 homocysteinylation

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    Background & Aims Several recent clinical studies have shown that serum homocysteine (Hcy) levels are positively correlated, while vitamin B12 (B12) and folate levels are negative correlated, with non-alcoholic steatohepatitis (NASH) severity. However, it is not known whether hyperhomocysteinemia (HHcy) plays a pathogenic role in NASH. Methods We examined the effects of HHcy on NASH progression, metabolism, and autophagy in dietary and genetic mouse models, patients, and primates. We employed vitamin B12 (B12) and folate (Fol) to reverse NASH features in mice and cell culture. Results Serum Hcy correlated with hepatic inflammation and fibrosis in NASH. Elevated hepatic Hcy induced and exacerbated NASH. Gene expression of hepatic Hcy-metabolizing enzymes was downregulated in NASH. Surprisingly, we found increased homocysteinylation (Hcy-lation) and ubiquitination of multiple hepatic proteins in NASH including the key autophagosome/lysosome fusion protein, Syntaxin 17 (Stx17). This protein was Hcy-lated and ubiquitinated, and its degradation led to a block in autophagy. Genetic manipulation of Stx17 revealed its critical role in regulating autophagy, inflammation and fibrosis during HHcy. Remarkably, dietary B12/Fol, which promotes enzymatic conversion of Hcy to methionine, decreased HHcy and hepatic Hcy-lated protein levels, restored Stx17 expression and autophagy, stimulated β -oxidation of fatty acids, and improved hepatic histology in mice with pre-established NASH. Conclusions HHcy plays a key role in the pathogenesis of NASH via Stx17 homocysteinylation. B12/folate also may represent a novel first-line therapy for NASH. Lay summary The incidence of non-alcoholic steatohepatitis, for which there are no approved pharmacological therapies, is increasing, posing a significant healthcare challenge. Herein, based on studies in mice, primates and humans, we found that dietary supplementation with vitamin B12 and folate could have therapeutic potential for the prevention or treatment of non-alcoholic steatohepatitis

    Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

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    Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

    Rising rural body-mass index is the main driver of the global obesity epidemic in adults

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    Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    A century of trends in adult human height

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    Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

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    From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

    Study of process responses, intermetallic formation and reliability of palladium-coated copper wire bonds

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    This thesis aims to address the knowledge gaps in terms of bondability, intermetallic formation and corrosion performance between palladium-coated Cu (Pd-Cu) and bare Cu wire bonds. The research specifically targets industrial fine pitch interconnect applications where a bonding wire (bare Cu and Pd-Cu) of approximately 15 μm diameter is used. In this research project, the effect of key process parameters such as Electronic Flame Off (EFO) current and cover gas type on the palladium distribution in Pd-Cu Free Air Ball (FAB) and bonded balls was studied. It was observed that Electronic Flame Off (EFO) current has a significant effect on the palladium distribution in Pd-Cu FABs. In addition, the hardness of Pd-Cu FABs is strongly affected by the EFO current and palladium distribution. Cu-Al intermetallic compounds (IMCs), typically CuAl2, CuAl and Cu9Al4 can be present between copper bonded ball and aluminum metallization in the as-bonded state and after thermal annealing. Bulk alloys of Cu and Cu-Al IMCs with varying concentrations of palladium (0, 1, 3 and 10 wt.% replacement of Cu) were prepared. The mechanical properties of these Cu and Cu-Al IMCs were studied using nano-indentation. Effects of the addition of palladium on these mechanical properties were also investigated. Among the three Cu-Al IMCs studied, CuAl (H~8.5 GPa) was found to be much harder than CuAl2 and Cu9Al4 (H~6.0 GPa). Young’s moduli of CuAl and Cu9Al4 IMCs were around 155 GPa and are much stiffer than the one for CuAl2 (~110 GPa). The addition of a few percent of Pd only slightly increases the hardness and Young’s modulus of the IMCs. The humidity reliability of bulk Cu, Al and the Cu-Al IMCs with various concentrations of Pd addition was investigated using a conventional three-electrode cell and an acidic chloride solution as the electrolyte. Among the three Cu-Al IMCs, Cu9Al4 has the highest corrosion rate followed by CuAl2 and CuAl. Pure Al is also more easily corroded than pure Cu. Palladium was shown to slightly improve the corrosion resistance of the metals and the Cu-Al IMCs. Interfacial evolution and bond reliability in Pd-Cu wire bonds during isothermal annealing at 175°C was investigated and compared to that of bare Cu wire bonds. The IMC thickness for Pd-Cu bonds with Pd at the bond interface was found to be thinner as compared to that for Pd-Cu wire bonds with no Pd at the bond interface. The presence of palladium at the bond interface has slowed down the IMC growth. Corresponding bond pull test finds that Pd-Cu wire bonds with Pd at the bond interface have best preserved the bond strength after long hours of annealing due to the beneficial presence of Pd. This research project provides fundamental information on the bondability, intermetallic growth and corrosion susceptibility of Pd-Cu wire bonds which will be useful to ensure good quality Pd-Cu wire bonding and reliability. Pd addition was shown to improve the corrosion resistance and thermal reliability of copper wire bonds, and its distribution can be controlled through the bonding process. Based on the generated understandings, guidelines for packaging engineers for reliable bonding using Pd-coated Cu bonding wires were generated.DOCTOR OF PHILOSOPHY (MSE

    A study of the factors affecting consumers' choice of coffee cafes and its implications on coffee cafes operators

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    This paper aims to find out what people really look for when deciding which coffee cafes to go to, the implications for coffee cafes’ managers as well as the future trends of coffee cafes. The methodology utilised and the survey data obtained are presented along with a final analysis of the variables that affect consumers’ choice of coffee cafes. Under the research methodology section, the research design, sampling procedures and the data collection method will be touched on

    Comparison study of mainland Chinese and Western travelers to Singapore.

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    The study is to find out the differences between the two groups of travelers to Singapore. The differences are drawn specifically with reference to their level of satisfaction and importance
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