Punching shear behavior of fiber reinforced polymers reinforced concrete flat slabs: experimental study

This paper presents the results of a two-phase experimental program investigating the punching shear behavior of fiber reinforced polymer reinforced concrete (FRP RC) flat slabs with and without carbon fiber reinforced polymer (CFRP) shear reinforcement. In the first phase, problems of bond slip and crack localization were identified. Decreasing the flexural bar spacing in the second phase successfully eliminated those problems and resulted in punching shear failure of the slabs. However, CFRP shear reinforcement was found to be inefficient in enhancing significantly the slab capacity due to its brittleness. A model, which accurately predicts the punching shear capacity of FRP RC slabs without shear reinforcement, is proposed and verified. For slabs with FRP shear reinforcement, it is proposed that the concrete shear resistance is reduced, but a strain limit of 0.0045 is recommended as maximum strain for the reinforcement. Comparisons of the slab capacities with ACI 318-95, ACI 440-98, and BS 8110 punching shear code equations, modified to incorporate FRP reinforcement, show either overestimated or conservative results

RNA:protein ratio of the unicellular organism as a characteristic of phosphorous and nitrogen stoichiometry and of the cellular requirement of ribosomes for protein synthesis

Background Mean phosphorous:nitrogen (P:N) ratios and relationships of P:N ratios with the growth rate of organisms indicate a surprising similarity among and within microbial species, plants, and insect herbivores. To reveal the cellular mechanisms underling this similarity, the macromolecular composition of seven microorganisms and the effect of specific growth rate (SGR) on RNA:protein ratio, the number of ribosomes, and peptide elongation rate (PER) were analyzed under different conditions of exponential growth. Results It was found that P:N ratios calculated from RNA and protein contents in these particular organisms were in the same range as the mean ratios reported for diverse organisms and had similar positive relationships with growth rate, consistent with the growth-rate hypothesis. The efficiency of protein synthesis in microorganisms is estimated as the number of active ribosomes required for the incorporation of one amino acid into the synthesized protein. This parameter is calculated as the SGR:PER ratio. Experimental and theoretical evidence indicated that the requirement of ribosomes for protein synthesis is proportional to the RNA:protein ratio. The constant of proportionality had the same values for all organisms, and was derived mechanistically from the characteristics of the protein-synthesis machinery of the cell (the number of nucleotides per ribosome, the average masses of nucleotides and amino acids, the fraction of ribosomal RNA in the total RNA, and the fraction of active ribosomes). Impairment of the growth conditions decreased the RNA:protein ratio and increased the overall efficiency of protein synthesis in the microorganisms. Conclusion Our results suggest that the decrease in RNA:protein and estimated P:N ratios with decrease in the growth rate of the microorganism is a consequence of an increased overall efficiency of protein synthesis in the cell resulting from activation of the general stress response and increased transcription of cellular maintenance genes at the expense of growth related genes. The strong link between P:N stoichiometry, RNA:protein ratio, ribosomal requirement for protein synthesis, and growth rate of microorganisms indicated by the study could be used to characterize the N and P economy of complex ecosystems such as soils and the oceans

Pathogenic Carboxyl Ester Lipase (CEL) Variants Interact with the Normal CEL Protein in Pancreatic Cells

Mutations in the gene encoding the digestive enzyme carboxyl ester lipase (CEL) are linked to pancreatic disease. The CEL variant denoted CEL-HYB predisposes to chronic pancreatitis, whereas the CEL-MODY variant causes MODY8, an inherited disorder of endocrine and exocrine pancreatic dysfunction. Both pathogenic variants exhibit altered biochemical and cellular properties compared with the normal CEL protein (CEL-WT, wild type). We here aimed to investigate effects of CEL variants on pancreatic acinar and ductal cell lines. Following extracellular exposure, CEL-HYB, CEL-MODY, and CEL-WT were endocytosed. The two pathogenic CEL proteins significantly reduced cell viability compared with CEL-WT. We also found evidence of CEL uptake in primary human pancreatic acinar cells and in native ductal tissue. Moreover, coexpression of CEL-HYB or CEL-MODY with CEL-WT affected secretion of the latter, as CEL-WT was observed to accumulate intracellularly to a higher degree in the presence of either pathogenic variant. Notably, in coendocytosis experiments, both pathogenic variants displayed a modest effect on cell viability when CEL-WT was present, indicating that the normal protein might diminish toxic effects conferred by CEL-HYB and CEL-MODY. Taken together, our findings provide valuable insight into how the pathogenic CEL variants predispose to pancreatic disease and why these disorders develop slowly over time.publishedVersio

Polymorphous low-grade adenocarcinoma of the upper lip: 11 cases of an uncommon diagnosis

ObjectiveThe aim of this case study was to describe an international case series of polymorphous low-grade adenocarcinoma (PLGA) affecting the upper lip.Material and MethodsOver a 30-year-period, the files of five pathology services were reviewed for PLGA affecting the upper lip. Hematoxylin and eosin–stained slides were reviewed by three oral and maxillofacial pathologists, and microscopic features were described. Clinical data were retrieved from patients' medical records.ResultsThe review identified 11 cases of upper lip PLGAs, with a complete set of clinical data available for 5 cases. There was a male predominance (1.2:1), and the mean age was 58.7 years. Most cases presented as small asymptomatic swellings that resembled benign tumors. All patients underwent surgery, and no recurrences or metastases were reported in the 8 cases from which follow-up data were available. Microscopically, the typical polymorphic architectural arrangement of PLGA was seen in all cases, with lobular, trabecular, papillary, and cribriform patterns identified. Perineural invasion, normal gland entrapment, Indian filing, and concentric growth were frequently identified.ConclusionPLGA must be included in the list of differential diagnoses of tumors affecting the upper lip because of its similar clinical presentation to benign entities. The follow-up data available from 8 of 11 cases suggest that these tumors follow a low-grade clinical course, similar to the majority of palatal cases of PLGA

Public data and open source tools for multi-assay genomic investigation of disease

Molecular interrogation of a biological sample through DNA sequencing, RNA and microRNA profiling, proteomics and other assays, has the potential to provide a systems level approach to predicting treatment response and disease progression, and to developing precision therapies. Large publicly funded projects have generated extensive and freely available multi-assay data resources; however, bioinformatic and statistical methods for the analysis of such experiments are still nascent. We review multi-assay genomic data resources in the areas of clinical oncology, pharmacogenomics and other perturbation experiments, population genomics and regulatory genomics and other areas, and tools for data acquisition. Finally, we review bioinformatic tools that are explicitly geared toward integrative genomic data visualization and analysis. This review provides starting points for accessing publicly available data and tools to support development of needed integrative methods

A four-helix bundle stores copper for methane oxidation

Methane-oxidising bacteria (methanotrophs) require large quantities of copper for the membrane-bound (particulate) methane monooxygenase (pMMO). Certain methanotrophs are also able to switch to using the iron-containing soluble MMO (sMMO) to catalyse methane oxidation, with this switchover regulated by copper. MMOs are Nature’s primary biological mechanism for suppressing atmospheric levels of methane, a potent greenhouse gas. Furthermore, methanotrophs and MMOs have enormous potential in bioremediation and for biotransformations producing bulk and fine chemicals, and in bioenergy, particularly considering increased methane availability from renewable sources and hydraulic fracturing of shale rock. We have discovered and characterised a novel copper storage protein (Csp1) from the methanotroph Methylosinus trichosporium OB3b that is exported from the cytosol, and stores copper for pMMO. Csp1 is a tetramer of 4-helix bundles with each monomer binding up to 13 Cu(I) ions in a previously unseen manner via mainly Cys residues that point into the core of the bundle. Csp1 is the first example of a protein that stores a metal within an established protein-folding motif. This work provides a detailed insight into how methanotrophs accumulate copper for the oxidation of methane. Understanding this process is essential if the wide-ranging biotechnological applications of methanotrophs are to be realised. Cytosolic homologues of Csp1 are present in diverse bacteria thus challenging the dogma that such organisms do not use copper in this location

The mTOR regulated RNA-binding protein LARP1 requires PABPC1 for guided mRNA interaction.

The mammalian target of rapamycin (mTOR) is a critical regulator of cell growth, integrating multiple signalling cues and pathways. Key among the downstream activities of mTOR is the control of the protein synthesis machinery. This is achieved, in part, via the co-ordinated regulation of mRNAs that contain a terminal oligopyrimidine tract (TOP) at their 5'ends, although the mechanisms by which this occurs downstream of mTOR signalling are still unclear. We used RNA-binding protein (RBP) capture to identify changes in the protein-RNA interaction landscape following mTOR inhibition. Upon mTOR inhibition, the binding of LARP1 to a number of mRNAs, including TOP-containing mRNAs, increased. Importantly, non-TOP-containing mRNAs bound by LARP1 are in a translationally-repressed state, even under control conditions. The mRNA interactome of the LARP1-associated protein PABPC1 was found to have a high degree of overlap with that of LARP1 and our data show that PABPC1 is required for the association of LARP1 with its specific mRNA targets. Finally, we demonstrate that mRNAs, including those encoding proteins critical for cell growth and survival, are translationally repressed when bound by both LARP1 and PABPC1

Patterns of lung cancer mortality in 23 countries: Application of the Age-Period-Cohort model

BACKGROUND: Smoking habits do not seem to be the main explanation of the epidemiological characteristics of female lung cancer mortality in Asian countries. However, Asian countries are often excluded from studies of geographical differences in trends for lung cancer mortality. We thus examined lung cancer trends from 1971 to 1995 among men and women for 23 countries, including four in Asia. METHODS: International and national data were used to analyze lung cancer mortality from 1971 to 1995 in both sexes. Age-standardized mortality rates (ASMR) were analyzed in five consecutive five-year periods and for each five-year age group in the age range 30 to 79. The age-period-cohort (APC) model was used to estimate the period effect (adjusted for age and cohort effects) for mortality from lung cancer. RESULTS: The sex ratio of the ASMR for lung cancer was lower in Asian countries, while the sex ratio of smoking prevalence was higher in Asian countries. The mean values of the sex ratio of the ASMR from lung cancer in Taiwan, Hong Kong, Singapore, and Japan for the five 5-year period were 2.10, 2.39, 3.07, and 3.55, respectively. These values not only remained quite constant over each five-year period, but were also lower than seen in the western countries. The period effect, for lung cancer mortality as derived for the 23 countries from the APC model, could be classified into seven patterns. CONCLUSION: Period effects for both men and women in 23 countries, as derived using the APC model, could be classified into seven patterns. Four Asian countries have a relatively low sex ratio in lung cancer mortality and a relatively high sex ratio in smoking prevalence. Factors other than smoking might be important, especially for women in Asian countries

Health and working conditions of pregnant women working inside and outside the home in Mexico City

BACKGROUND: To explore differences related to health and working conditions by comparing socio-demographic parameters, reproductive and prenatal care characteristics and working conditions among pregnant women who are employed outside the home (extra-domestic) while still performing a domestic workload versus those who perform exclusively domestic work in the home (intra-domestic). METHODS: A cross-sectional study was carried out at Family Medicine Unit N 31 of the Mexican Institute of Social Security (IMSS) in Mexico City between April and July 2003. Interviews were conducted with 537 pregnant women engaged in either extra-domestic work plus intra-domestic tasks, or those performing strictly intra-domestic work. Information was obtained regarding their demographic status, prenatal care, reproductive, work characteristics, and health during pregnancy. RESULTS: One hundred ninety-six (36.5%) of the interviewed women had paid jobs outside the home in addition to domestic tasks, while three hundred forty-one (63.5 %) engaged in exclusively intra-domestic occupations. Of the women with paid jobs, 78.6% worked as clerks. Among domestic tasks, we found that the greatest workload was associated with washing of clothes, and our micro-ergonomic analysis revealed that women who worked strictly inside the home had a higher domestic workload versus employed women (69.2 vs. 44.9%). When we analyzed the effect of work on health during pregnancy, we observed that women who worked strictly inside the home were at a higher risk for musculoskeletal and genitourinary symptoms than those employed outside the home. CONCLUSION: These findings suggest that the effect of intra-domestic work should not be ignored when considering women's health during pregnancy, and that greater attention should be paid to women's working conditions during intra and extra-domestic work

The Jamaica asthma and allergies national prevalence survey: rationale and methods

<p>Abstract</p> <p>Background</p> <p>Asthma is a significant public health problem in the Caribbean. Prevalence surveys using standardized measures of asthma provide valid prevalence estimates to facilitate regional and international comparisons and monitoring of trends. This paper describes methods used in the Jamaica Asthma and Allergies National Prevalence Survey, challenges associated with this survey and strategies used to overcome these challenges.</p> <p>Methods/Design</p> <p>An island wide, cross-sectional, community-based survey of asthma, asthma symptoms and allergies was done among adults and children using the European Community Respiratory Health Survey Questionnaire for adults and the International Study of Asthma and Allergies in Children. Stratified multi-stage cluster sampling was used to select 2, 163 adults aged 18 years and older and 2, 017 children aged 2-17 years for the survey. The Kish selection table was used to select one adult and one child per household. Data analysis accounted for sampling design and prevalence estimates were weighted to produce national estimates.</p> <p>Discussion</p> <p>The Jamaica Asthma and Allergies National Prevalence Survey is the first population- based survey in the Caribbean to determine the prevalence of asthma and allergies both in adults and children using standardized methods. With response rates exceeding 80% in both groups, this approach facilitated cost-effective gathering of high quality asthma prevalence data that will facilitate international and regional comparison and monitoring of asthma prevalence trends. Another unique feature of this study was the partnership with the Ministry of Health in Jamaica, which ensured the collection of data relevant for decision-making to facilitate the uptake of research evidence. The findings of this study will provide important data on the burden of asthma and allergies in Jamaica and contribute to evidence-informed planning of comprehensive asthma management and education programs.</p