Aberrant glycosylation associated with enzymes as cancer biomarkers

<p>Abstract</p> <p>Background</p> <p>One of the new roles for enzymes in personalized medicine builds on a rational approach to cancer biomarker discovery using enzyme-associated aberrant glycosylation. A hallmark of cancer, aberrant glycosylation is associated with differential expressions of enzymes such as glycosyltransferase and glycosidases. The aberrant expressions of the enzymes in turn cause cancer cells to produce glycoproteins with specific cancer-associated aberrations in glycan structures.</p> <p>Content</p> <p>In this review we provide examples of cancer biomarker discovery using aberrant glycosylation in three areas. First, changes in glycosylation machinery such as glycosyltransferases/glycosidases could be used as cancer biomarkers. Second, most of the clinically useful cancer biomarkers are glycoproteins. Discovery of specific cancer-associated aberrations in glycan structures of these existing biomarkers could improve their cancer specificity, such as the discovery of AFP-L3, fucosylated glycoforms of AFP. Third, cancer-associated aberrations in glycan structures provide a compelling rationale for discovering new biomarkers using glycomic and glycoproteomic technologies.</p> <p>Summary</p> <p>As a hallmark of cancer, aberrant glycosylation allows for the rational design of biomarker discovery efforts. But more important, we need to translate these biomarkers from discovery to clinical diagnostics using good strategies, such as the lessons learned from translating the biomarkers discovered using proteomic technologies to OVA 1, the first FDA-cleared In Vitro Diagnostic Multivariate Index Assay (IVDMIA). These lessons, providing important guidance in current efforts in biomarker discovery and translation, are applicable to the discovery of aberrant glycosylation associated with enzymes as cancer biomarkers as well.</p

Developing a Holistic Fire Risk Assessment Framework for Building Construction Sites in Hong Kong

Amongst all types of construction accidents, industrial practitioners tend to pay less attention to the prevention of fires at construction sites.  Although fires may not occur frequently on construction sites, statistics show that when they do, the consequences are very serious; involving fatalities, injuries, serious project delays and financial loss.  There are many reasons why fires occur on sites, but a simple lack of awareness of the risks of fire is a major contributor.  Fire risk assessment is not commonly performed on sites.  Hence, it is believed that an appropriate assessment method for evaluating potential fire risk is required in order to improve the awareness of fire risk on construction sites.  This paper reports on the key findings of a research project which aims to develop a comprehensive, objective, reliable, and practical fire risk assessment framework for building construction sites based in Hong Kong.  A comprehensive list of those factors (or conditions) which may constitute a fire risk was compiled using desktop research and structured face-to-face interviews with experienced site personnel.  This list of factors was then used to develop a questionnaire survey form and the Reliability Interval Method (RIM) was used to analyse the survey results and determine the relative importance and rankings of the various fire risk factors at a broad level and risk sub-factors at a detailed level.  It was found that the fire risk factor of “Fire Services Equipment and Installations” has the greatest impact on construction site fire safety, with “Means of Escape in Case of Fire” being the second, and “Attitude of Main Contractor towards Fire Safety” being the third.  In fact, it is the main contractor who plays the pivotal role in maintaining construction site fire safety, which is in line with the high ranking given to the fire risk factor of “Attitude of Main Contractor towards Fire Safety”.  The proposed fire risk assessment framework can be used to develop a useful checklist for assessing the overall level of fire risk for a construction site, and to identify any areas needing improvement.  Although the fire risk assessment framework was developed locally in Hong Kong, the research methodology could be replicated in other countries to produce similar frameworks for international comparison.  Such an extension would aid the understanding of the management of fire risk on construction sites and help discover differences between countries

Development and analytical performance evaluation of an automated chemiluminescent immunoassay for pro-gastrin releasing peptide (ProGRP)

Background: Pro-gastrin releasing peptide ( ProGRP) concentrations in blood play an important role in the diagnosis and treatment of patients with small cell lung cancer (SCLC). The automated quantitative ARCHITECT (R) ProGRP assay was developed to aid in the differential diagnosis and in the management of SCLC. The purpose of this study was to evaluate the analytical performance of this chemiluminescent microparticle immunoassay at multiple sites. Methods: ARCHITECT ProGRP measures ProGRP using a two-step sandwich using monoclonal anti-ProGRP antibodies coated on paramagnetic microparticles and labeled with acridinium. Analytical performance of the assay was evaluated at four sites: Abbott Japan, Denka Seiken, the Johns Hopkins University, and the University of Munich. Results: Total precision (%CV) for nine analyte concentrations was between 2.2 and 5.7. The analytical sensitivity of the assay was between 0.20 pg/mL and 0.88 pg/mL. The functional sensitivity at 20% CV was between 0.66 pg/mL and 1.73 pg/mL. The assay was linear up to 50,000 pg/mL using a 1:10 autodilution protocol. The calibration curve was stable for 30 days. Comparison with the Fujirebio microtiter plate enzyme-linked immunosorbent assay (EIA) ProGRP assay gave a slope of 0.93 and a correlation coefficient (r) of 0.99. Conclusions: These results demonstrate that the ARCHITECT ProGRP assay has excellent sensitivity, precision, and correlation to a reference method. This assay provides a convenient automated method for ProGRP measurement in serum and plasma in hospitals and clinical laboratories. Clin Chem Lab Med 2009;47:1557-63

Thiol-yne \u27Click\u27 Chemistry As a Route to Functional Lipid Mimetics

Thiol-alkyne \u27click\u27 chemistry is a modular, efficient mechanism to synthesize complex A2B 3-arm star polymers. This general motif is similar to a phospholipid where the A blocks correspond to lypophilic chains and the B block represents the polar head group. In this communication we employ thiol-yne chemistry to produce polypeptide-based A2B lipid mimetics. The utility of the thiol-yne reaction is demonstrated by using a divergent and a convergent approach in the synthesis. These polymers self-assemble in aqueous solution into spherical vesicles with a relatively narrow size distribution independent of block composition over the range studied. Using the thiol-yne convergent synthesis, we envision a modular approach to functionalize proteins or oligopeptides with lipophilic chains that can imbed seamlessly into a cell membrane

Key drivers for smart and sustainable practices in the built environment

PurposeThe construction industry has been evolving in recent years through the adoption of smart tools such as building information modeling to reduce the complexity in the construction process and optimize the project's goals. This paper aims to identify and assess the key drivers for the implementation of smart sustainable practices in the construction industry.Design/methodology/approachInferential and descriptive statistical techniques were employed in analyzing the data collected via an international empirical questionnaire survey deployed in soliciting the perceptions of 220 construction professionals across 21 countries. Factor analysis was used to categorize the identified key drivers into their underlying clusters for further discussion. Also, the data were analyzed based on the various groups and regions of the study's respondents.FindingsThe key drivers (KDs) are related to the technical competence of staff as well as knowledge and awareness level within the industry, issues related to organizational and project's strategy and policies, availability of financial resources and development of relevant standards and policies to aid its execution among others. A comparative analysis of the perceptions of the different respondents' groups was undertaken and discussed.Practical implicationsThe analysis of the key drivers for the implementation of smart and sustainable practices in the construction industry is expected to aid the decision-making of the relevant stakeholders as well as serve as a consultation instrument for government agencies in their design of localized policies and guidelines to aid smart and sustainable urbanization. The findings revealed the gaps in the implementation of smart and sustainable practices in various climes and organization setups and provided useful and practical strategies for addressing the current hindrances during implementation.Originality/valueThe study has generated valuable insights into the significant drivers that can enhance the implementation of smart and sustainable practices across regions. It is evident that synergy among the relevant stakeholders in the built environment will help accelerate the implementation of smart sustainable practices in the construction industry. The study findings have provided profound contributions to theory and research as well as to industry practice

CFD analysis of turbopump volutes

An effort is underway to develop a procedure for the regular use of CFD analysis in the design of turbopump volutes. Airflow data to be taken at NASA Marshall will be used to validate the CFD code and overall procedure. Initial focus has been on preprocessing (geometry creation, translation, and grid generation). Volute geometries have been acquired electronically and imported into the CATIA CAD system and RAGGS (Rockwell Automated Grid Generation System) via the IGES standard. An initial grid topology has been identified and grids have been constructed for turbine inlet and discharge volutes. For CFD analysis of volutes to be used regularly, a procedure must be defined to meet engineering design needs in a timely manner. Thus, a compromise must be established between making geometric approximations, the selection of grid topologies, and possible CFD code enhancements. While the initial grid developed approximated the volute tongue with a zero thickness, final computations should more accurately account for the geometry in this region. Additionally, grid topologies will be explored to minimize skewness and high aspect ratio cells that can affect solution accuracy and slow code convergence. Finally, as appropriate, code modifications will be made to allow for new grid topologies in an effort to expedite the overall CFD analysis process

Exhaled Nitric Oxide is Not a Biomarker for Pulmonary Tuberculosis.

To reduce transmission of tuberculosis (TB) in resource-limited countries where TB remains a major cause of mortality, novel diagnostic tools are urgently needed. We evaluated the fractional concentration of exhaled nitric oxide (FeNO) as an easily measured, noninvasive potential biomarker for diagnosis and monitoring of treatment response in participants with pulmonary TB including multidrug resistant-TB in Lima, Peru. In a longitudinal study however, we found no differences in baseline median FeNO levels between 38 TB participants and 93 age-matched controls (13 parts per billion [ppb] [interquartile range (IQR) = 8-26] versus 15 ppb [IQR = 12-24]), and there was no change over 60 days of treatment (15 ppb [IQR = 10-19] at day 60). Taking this and previous evidence together, we conclude FeNO is not of value in either the diagnosis of pulmonary TB or as a marker of treatment response