The topography of DNA methylation in the non-neoplastic colonic mucosa surrounding colorectal cancers

The degree of gene hypermethylation in non-neoplastic colonic mucosa (NNCM) is a potentially important event in the development of colorectal cancer (CRC), particularly for the subgroup with a CpG island methylator phenotype (CIMP). In this study, we aimed to use an unbiased and high-throughput approach to evaluate the topography of DNA methylation in the non-neoplastic colonic mucosa (NNCM) surrounding colorectal cancer (CRC). A total of 61 tissue samples comprising 53 NNCM and 8 tumor samples were obtained from hemicolectomy specimens of two CRC patients (Cases 1 and 2). NNCM was stripped from the underlying colonic wall and samples taken at varying distances from the tumor. The level of DNA methylation in NNCM and tumor tissues was assessed at 1,505 CpG sites in 807 cancer-related genes using Illumina GoldenGate® methylation arrays. Case 1 tumor showed significantly higher levels of methylation compared to surrounding NNCM samples (P?

Overexpression of neurone glial-related cell adhesion molecule is an independent predictor of poor prognosis in advanced colorectal cancer

A downstream target of the Wnt pathway, neurone glial-related cell adhesion molecule (Nr-CAM) has recently been implicated in human cancer development. However, its role in colorectal cancer (CRC) pathobiology and clinical relevance remains unknown. In this study, we examined the clinical significance of Nr-CAM protein expression in a retrospective series of 428 CRCs using immunohistochemistry and tissue microarrays. Cox proportional hazards regression was used to calculate hazard ratios (HR) of mortality according to various clinicopathological features and molecular markers. All CRC samples were immunoreactive for Nr-CAM protein expression, compared to 10 / 245 (4%) matched normal tissue (P <0.0001). Of 428 CRC samples, 97 (23%) showed Nr-CAM overexpression, which was significantly associated with nodal (P = 0.012) and distant (P = 0.039) metastasis, but not with extent of local invasion or tumor size. Additionally, Nr-CAM overexpression was associated with vascular invasion (P = 0.0029), p53 expression (P = 0.036), and peritoneal metastasis at diagnosis (P = 0.013). In a multivariate model adjusted for other clinicopathological predictors of survival, Nr-CAM overexpression correlated with a significant increase in disease-specific (HR 1.66; 95% confidence interval 1.11-2.47; P = 0.014) and overall mortality (HR 1.57; 95% confidence interval 1.07-2.30; P = 0.023) in advanced but not early stage disease. Notably, 5-fluorouracil-based chemotherapy conferred significant survival benefit to patients with tumors negative for Nr-CAM overexpression but not to those with Nr-CAM overexpressed tumors. In conclusion, Nr-CAM protein expression is upregulated in CRC tissues. Nr-CAM overexpression is an independent marker of poor prognosis among advanced CRC patients, and is a possible predictive marker for non-beneficence to 5-fluorouracil- based chemotherapy.

Development and Validation of a Compact Thermal Model for an Aircraft Compartment

The development of accurate structural/thermal numerical models of complex systems, such as aircraft fuselage barrels, is often limited and determined by the smallest scales that need to be modelled. The development of reduced order models of the smallest scales and consequently their integration with higher level models can be a way to minimise the bottle neck present, while still having efficient, robust and accurate numerical models. In this paper a methodology on how to develop compact thermal fluid models (CTFMs) for compartments where mixed convection regimes are present is demonstrated. Detailed numerical simulations (CFD) have been developed for an aircraft crown compartment and validated against experimental data obtained from a 1:1 scale compartment rig. The crown compartment is defined as the confined area between the upper fuselage and the passenger cabin in a single aisle commercial aircraft. CFD results were utilised to extract average quantities (temperature and heat fluxes) and characteristic parameters (heat transfer coefficients) to generate CTFMs. The CTFMs have then been compared with the results obtained from the detailed models showing average errors for temperature predictions lower than 5%. This error can be deemed acceptable when compared to the nominal experimental error associated with the thermocouple measurements.

The CTFMs methodology developed allows to generate accurate reduced order models where accuracy is restricted to the region of Boundary Conditions applied. This limitation arises from the sensitivity of the internal flow structures to the applied boundary condition set. CTFMs thus generated can be then integrated in complex numerical modelling of whole fuselage sections.

Further steps in the development of an exhaustive methodology would be the implementation of a logic ruled based approach to extract directly from the CFD simulations numbers and positions of the nodes for the CTFM.

Observation of Ultrafast Charge Migration in an Amino Acid

We present the first direct measurement of ultrafast charge migration in a biomolecular building block the amino acid phenylalanine. Using an extreme ultraviolet pulse of 1.5 fs duration to ionize molecules isolated in the gas phase, the location of the resulting hole was probed by a 6 fs visible/near-infrared pulse. By measuring the yield of a doubly charged ion as a function of the delay between the two pulses, the positive hole was observed to migrate to one end of the cation within 30 fs. This process is likely to originate from even faster coherent charge oscillations in the molecule being dephased by bond stretching which eventually localizes the final position of the charge. This demonstration offers a clear template for observing and controlling this phenomenon in the future.

Pigmented paravenous chorioretinal atrophy is associated with a mutation within the crumbs homolog 1 (CRB1) gene

Pigmented paravenous chorioretinal atrophy (PPCRA) is an unusual retinal degeneration characterized by accumulation of pigmentation along retinal veins. The purpose of this study was to describe the phenotype of a family with PPCRA, determine the mode of inheritance, and identify the causal mutation.

Supply Chain Management in Confined Site Construction: Strategies to Reduce Delay in the Delivery of Materials to Site

With the increase in construction in dense urban environments, the delays associated with managing the material supply chain to site is called into question. Purpose: The aim of this investigation is to gain the perspective of construction contractors operating in a dense urban environment and the resulting strategies adopted to reduce delays in the delivery of materials to site. Methodology: This is achieved through incorporating a comprehensive literature review on the subject in conjunction with industry interviews with construction professionals in the identification of various management issues and corresponding strategies in the reduction of delays in the delivery of materials to site. Findings: The key issue which emerges is the lack of space for unloading bays while the corresponding key strategy is to schedule deliveries outside peak congestion times. Practical Implication: With confined site construction evident throughout the industry and the noted importance of an effective supply chain, the findings here in further assist on-site management in the daily task of ensuring the effective delivery and off-loading of materials in a complex and hazardous environment. Originality/Value: This research aids on-site management of confined site environments in the coordination of the material supply chain to site.

Meeting the Requirements of the CDM Regulations: Identification of Critical Success Factors of Small to Medium Sized Contractor’ Compliance in the UK Construction Industry

The Construction Design and Management (CDM) Regulations (2007) is one of the most important set of health and safety regulations in the construction industry today. The aim of this research is to examine critical success factors for CDM compliance in small to medium size contractors in the UK construction industry. The objectives of the research include the identification of critical barriers in doing so along with the identification of success factors where CDM is incorporated. A mixed method approach is adopted in the identification and categorisation of the various factors encompassing a literature review, interviews and questionnaire survey. The key finding which emerge is the lack of knowledge and understanding with regards the CDM regulations with the recommendation to encourage small and medium contractor compliance through illustrating the benefits attainable. The practicality of the research is evident based on the significant uptake in the CDM by larger contractors, yet the research indicates that further insight and guidance is required to educate and inform those working within small to medium sized contractors in the UK. Where such acknowledgement and compliance is adopted, it is envisaged that this sector will benefit from reduced incidents and accidents, increased productivity while ultimately leading to a safer and more productive industry as a whole.

Confined Site Construction and its Impact on Personnel Productivity

Inner city, confined site construction is quickly becoming the norm within the construction sector. The aim of this paper is to identify and document the effect, if any, that a confined construction site environment has on the productivity of on-site personnel. In order to compile the relevant information and attain appropriate results on the matter in question, a qualitative analytical approach is adopted. This process incorporates multiple cases studies from Ireland, Northern Ireland and USA. From the resulting case studies, a minimum of three individual interviews and focus group seminars are conducted to aid in the collection of the data while also assisting in the confirmation of the factors identified from a critique of the relevant literature. From the resulting case studies and discussions, a list of the key issues pertaining to the on-site productivity of personnel emerged and is documented as follows; 1) Overcrowding of personnel at workstations, 2) Lack of space for the effective movement of personnel on-site, 3) Numerous trades working within the one space on-site. Through identifying the issues highlighted and proactively mitigating or eliminating the factors detailed, on-site management professionals can strive to ensure maximum productivity from the industry’s most important resource – people.

A Review of Meditation in the Irish Construction Industry: Critical Success Factors in Competencies and Processes

The construction industry notoriously excels at dispute creation – both in Ireland and world wide. This paper exams mediation in the Irish construction industry based around critical success factors in the competencies and processes required by mediators operating in the construction industry. Through conducting the relevant analysis, it was possible to extract and outline the resulting critical success factors in process and competencies of mediators in the Irish construction industry. This was achieved through a review of the literature, followed by detailed interviews from industry experts to elicit and highlight the core competencies required. To aid in the study, qualitative analysis using mind mapping software was adopted, thus assisting the identification of the key factors. Following analysis, facilitative mediation was identified as best suited for the industry in question; recommendations and experience were key for mediator selection and five and six factors were identified for mediator skills and mediation critical success factors respectively. The results returned are similar to those determined by authors in other countries and provide a good reference point for the development the industry. By following the findings of this report mediators and parties in dispute can improve processes and be more successful in outcomes. In this study the author shows that mediation is an effective and appropriate method of resolving disputes within the Irish construction industry.

Material Management in Confined Site Construction

The objective of this paper is to identify various managerial issues encountered and resulting strategies adopted, with regards management of materials on confined construction site. This is achieved through classifying the various managerial burdens encountered with the numerous strategies adopted, for the successful management of such confined environments within the realm of materials management.


Through conducting an extensive literature review and detailed interviews, a comprehensive insight into the materials management concerns within a confined construction site environment is envisaged and portrayed. The following are the leading issues highlighted; (1)Lack of adequate storage space, (2)Work place becoming over-crowded, (3)Lack of adequate room for the effective handling of materials and (4)Difficult to transport materials around site. The leading managerial strategies to the management of materials on confined construction sites may be listed in order of importance, as follows; (1)Pre-fabrication and pre-assembly, (2)Providing adequate storage, (3)Space scheduling, (4)Just-In-Time delivery techniques, and (5)Effective design site layout.

Based on the research conducted, it can be concluded, that through effective management of the issues identified along with implementing the various strategies highlighted; successful materials management within a confined construction site environment is attainable.


Innovative Aspect of Paper: An empirical study of three different construction sites in three different countries (Ireland, England and USA) investigating the managerial issues and strategies relating to implementation of materials management in confined construction sites.

Impact of Wind Generation Mix on Transient Stability for an Interconnected Power System

The rapid growth of wind generation in many European countries is pushing power systems into
uncharted territory. As additional wind generators are installed, the changing generation mix may
impact on power system stability. This paper adopts the New England 39 bus system as a test
system for transient stability analysis. Thermal generator models are based on a likely future plant
mix for existing systems, while varying capacities of fixed-speed induction generators (FSIG) and
doubly-fed induction generators (DFIG) are considered. The main emphasis here has been placed
on the impact of wind technology mix on inter-area oscillations following transient grid
disturbances. In addition, both rotor angle stability and transient voltage stability are examined, and
results are compared with current grid code requirements and standards. Results have shown that
FSIGs can reduce tie-line oscillations and improve damping following a transient disturbance, but
they also cause voltage stability and rotor angle stability problems at high wind penetrations. In
contrast, DFIGs can improve both voltage and rotor angle stability, but their power output
noticeably oscillates during disturbances.

Next generation sequencing-based molecular diagnosis of retinitis pigmentosa: identification of a novel genotype-phenotype correlation and clinical refinements

Retinitis pigmentosa (RP) is a devastating form of retinal degeneration, with significant social and professional consequences. Molecular genetic information is invaluable for an accurate clinical diagnosis of RP due to its high genetic and clinical heterogeneity. Using a gene capture panel that covers 163 of the currently known retinal disease genes, including 48 RP genes, we performed a comprehensive molecular screening in a collection of 123 RP unsettled probands from a wide variety of ethnic backgrounds, including 113 unrelated simplex and 10 autosomal recessive RP (arRP) cases. As a result, 61 mutations were identified in 45 probands, including 38 novel pathogenic alleles. Interestingly, we observed that phenotype and genotype were not in full agreement in 21 probands. Among them, eight probands were clinically reassessed, resulting in refinement of clinical diagnoses for six of these patients. Finally, recessive mutations in CLN3 were identified in five retinal degeneration patients, including four RP probands and one cone-rod dystrophy patient, suggesting that CLN3 is a novel non-syndromic retinal disease gene. Collectively, our results underscore that, due to the high molecular and clinical heterogeneity of RP, comprehensive screening of all retinal disease genes is effective in identifying novel pathogenic mutations and provides an opportunity to discover new genotype-phenotype correlations. Information gained from this genetic screening will directly aid in patient diagnosis, prognosis, and treatment, as well as allowing appropriate family planning and counseling.