Pharmacological characterization of chemokine receptor 7 (CCR7) as a potential therapeutic target in cancer

The expression of CCR7 was evaluated in different cancer cell lines by using flow cytometry, western blot, Immunofluorescence and immunohistochemistry. We showed for the selected cell lines that the expression is maintained in cells grown as spheroids, and xenoplanted in mice. Furthermore, we showed the expression of CCR7 correlates with stage of the disease in patient derived head and neck cancer tissue. We also showed that expression of CCR7 in cancer cell lines correlates with migratory aptitude towards CCL21 in a scratch assay, Boyden chamber assay and spheroid invasion assay. We then showed that the expression of CCR7 is elevated under serum starvation and under hypoxia in cancer cell lines grown as monolayers and as spheroids; and that there is a correlation between hypoxia and CCR7 expression in spheroids, xenografted cells and clinical cancer tissue. However, we found that in cell line OSC-19, the increase in the expression of CCR7 did not correlate to increased migration. Our investigations following this observation showed that whilst hypoxia increases the expression of CCR7, it concurrently causes a decrease in reactive oxygen species (ROS) which strongly abrogates migratory aptitude in OSC-19, resulting in an overall loss of migration in OSC-19 cells. In addition, we characterised OSC-19 as a suitable model to evaluate small molecule CCR7 antagonists using a number of different assays. In particular, we showed that ICT13069 antagonised response of this cell line across a number of drivers of malignancy such as migration, invasion in 2D and 3D models.Zarqa UniversityThe full text was made available at the end of the embargo, 3rd December 201

Understanding the cost of change Function: A basis for using an effective small step change strategy

This paper develops the cost of change function under the Continuous Improvement (CI) paradigm advocated by quality gurus such as Deming, Taguchi, and Shingo. CI is considered to be focusing on "frame bending" or minor changes while Organizational Change (OC) is considered to be focusing on "frame breaking " or major changes. The cost of change function is modified to be a discrete function incorporating a "monitoring" cost component and a "doing" cost element, which leads to a better understanding of the multiple tradeoffs: a) between the number of smaller steps to be taken to achieve the desired or planned change and the total cost of change, and b) between the total cost of change and the time needed to achieve the desired change. It is proposed to seek validation of the modified cost of change function by interviewing senior management personnel, who have project management and/or change management experience, such as managing six-sigma projects

Comparison between some meteorological elements measured by ECMWF and Earth stations in different regions in Iraq

The aim of this paper is to validate the data of three meteorological elements Air Temperature (Ta) , Relative Humidity (RH), Wind Speed (WS) from the European Center For-Medium Range Weather Forecasting (ECMWF) , against ground stations data using several Models at six stations well distributed in Iraq (Mosul, Kirkuk, Baghdad, Kut, Nasiriya, and Basra). Due to the difficulties which experienced by the ground climate stations in Iraq from a shortage of devices and equipment for measuring the various climatic elements, which led to a huge shortage of data throughout time for political, economic and natural disasters. It is found that researchers can adopt the data of satellite stations to monitor the climate because let’s found that there is a highly significance Correlations between the data of these stations and the data of the ground stations for climate monitoring Five Mathematical Models were used for that [Linear Models, Quadratic Models, Exponential Models, Logarithmic Models, and Power Models]. The performance of these models were evaluated by comparing the calculated (Ta, RH, WS) from earth stations. Those mathematical correlations help to be able to calculate the ground data in state of there is no ground climate stations data. Several statistical tests Correlation Coefficient (R), Coefficient of Determination (R2), Root Mean Square Error (RMSE), Mean Absolute Error (MAE) were used to control the validation and goodness of these Models. The R2 obtained from these Models were very high in all stations. This means that, there is a highly significance Correlations between (Ta, RH, WS) estimated and [Ta, RH, WS] measured in all statio

Influence of Exposure Environments on the Durability of Slag-Blended Cements

Both chlorides and sulphates combine in seawater to affect the durability of reinforced concrete structures located in marine environments. This paper presents the results of an experimental study on slag blended cement systems, cured for 7 days, before exposure to a combined solution of sodium chloride (30 g/L) and sodium sulphate (3 g/L). Two slags of different chemical compositions, designated as slags 1 and 2 were respectively blended with Portland cement CEM I 52.5R at 30 and 70 wt.% replacement levels. Mechanical tests on mortar samples were complemented by microstructural examination and chemical characterisation on paste samples, all using a constant w/b ratio of 0.5, to investigate the influence of exposure environment. The exposure environments include water and ponding in combined chloride-sulphate solution at 20 °C and 38 °C (to reflect temperate and tropical climates). The results show that temperature has a significant effect on the durability of slag blends. Reduced sorptivity at higher temperature led to reduced chloride penetration at early age. This effect is less so at later age. Compressive strength generally improved with increase in chloride penetration. SEM-EDX elemental analysis provided a good basis for following chloride penetration profile. XRD analysis showed the conversion of monosulphate to ettringite, Friedel’s salt and Kuzel’s salt upon exposure to salt solution, which possibly led to improved sorptivity and mechanical properties

Dam breach parameters and their influence on flood hydrographs for Mosul dam

Dams breach geometry prediction is crucial in dam break studies. The characteristics of flood hydrographs resulting from a dam breach essentially depend on the breach geometry and the required time for breach formation. To investigate the impact of breach parameters on maximum breaching outflows, five breach prediction approaches were implemented to calculate the flood hydrographs using HEC-RAS model, for Mosul dam. Numerous reservoir water levels for each approach were considered. Sensitivity analysis was carried out to evaluate the effect of each parameter on the resulting flood hydrographs. The time and value of peak discharge for each scenario were analysed and discussed. Results show that the most suitable method for estimating breach parameters for Mosul dam was the Froehlich approach. Furthermore, the sensitivity analysis shows that the breach side slope does not affect the peak discharge time and has a minor influence on peak outflow values. Meanwhile, the required time for the breach to develop was highly sensitive to both peak discharge and peak discharge time

Effects of Temperature and Curing Duration on the Stability of Slag Cements in Combined Chloride-Sulphate Environments

This experimental study investigates the effects of temperature and curing duration on the stability of slag blended cement systems exposed at 20 °C and 38 °C to combined sodium chloride (30 g/L) – sodium sulphate (3 g/L) solutions. Two slags, designated as slag 1 and 2, having CaO/SiO2 ratios of 1.05 and 0.94, were respectively blended with Portland cement CEM I 52.5R at 30 wt.% replacement level. Mortar prisms and cubes with w/b ratio of 0.5 and binder/aggregate ratio of 1:3 were then prepared for length and mass changes. The samples were cured in lime water for either 7 or 28 days before ponding for a total exposure period of 544 days. Analogous paste samples were also prepared to follow changes in the hydration products using x-ray diffraction (XRD). The results showed that curing at 38°C resulted in less expansion and prolonged curing generally reduced expansion except for slag 1 blend at 20 °C. Also, mass-change was minimal at 38 °C compared to 20 °C, and curing up to 28 days further improved mass stability. There was a positive correlation between mass change and length change for the period of investigation

Engineering Performance of a New Siloxane-Based Corrosion Inhibitor

This paper presents an evaluation of a new non-toxic corrosion inhibitor on selected engineering properties of concrete mixes with different cementitious materials following a corrosion and durability study on concrete samples. Corrosion inhibitors consist of powders or solutions which are added to concrete when mixed to prevent or delay corrosion of steel by their reaction with ferrous ions to form a stable and passive ferric oxide film on the steel surface. The new inhibitor functions slightly differently and its corrosion inhibition effect is due to the formation of a siloxane coating on the steel surface. Therefore, the performance of the new inhibitor in concrete mixes manufactured with CEM I, PFA and GGBS cements was compared against a well known and established corrosion inhibitor on the market, namely calcium nitrite in terms of their effect on workability (measured in terms of slump), compressive strength, freeze–thaw durability and macro-cell corrosion. The results from this experimental programme have demonstrated that the new inhibitor is effective in reducing or slowing down corrosion. In addition, it was found that CEM I concrete containing the new inhibitor was less penetrable to chlorides than that without. A similar set of results was obtained for the freeze– thaw resistance, but the compressive strength was found to decrease with the addition of the new inhibitor. In the case of concretes containing PFA and GGBS, the new inhibitor was found to be less effective. Further, long-term investigations are recommended to assess the effectiveness over time

A Micro-Level Examination of the Impact of Rail Transit Investments on the Patterns of Firm Dynamics

Transit-oriented development has been increasingly implemented at stations of both existing and new fixed transit systems across the U.S. to stimulate local economy and create livable communities. A common belief among planners in favor of transit-oriented development is that the provision of passenger rail systems promotes urban development around rail stations. There is a lack of empirical evidence, however, that supports this presumption. To address the gap in relevant literature, this dissertation examines the impact of passenger rail stations on the four different patterns of firm dynamics in the State of Maryland—firm birth and inward relocation as positive impacts, and firm closure and outward relocation as negative impacts. This dissertation uses both standard and propensity-score-weighted negative binomial regression methods to analyze the dependent variables of firm dynamics constructed from the National Establishment Time Series (NETS) panel data of the State of Maryland from 1990 to 2010. By examining both positive and negative impacts of firm dynamics, this dissertation estimates the likelihood of firm retainment and net relocation for areas in proximity of the passenger rail stations, while controlling for a number of potentially confounding factors. Positive and statistically significant relationships are found between proximity to the passenger rail stations and the rates of firm births and inward relocating firms in Maryland, regardless of differences in the level of maturity of stations. From 1990 to 2010, the areas of passenger rail stations in Maryland experienced a wide range of rates of growth in firm density, depending on the year of station opening. The results of the four different patterns of firm dynamics suggest that areas near passenger rail stations gain belated economic benefits, well after the introduction of rail stations, shown by higher likelihood of firm retainment and net relocation around the mature rail stations opened before 1990. In comparison, areas near the less mature stations that opened after 1990 had predominantly lower likelihood of firm retainment and net firm relocation. Planners and policymakers should be proactive in directing development near rail stations by adopting a variety of measures and policies that support or at least consistent with transit-oriented development

Methods of assessing the durability and service life of concrete structures

Characterisation of cover concrete is often the most viable means for assessing the durability and has become increasingly evident over the past 20 years. A variety of field methods and laboratory techniques exist, which provide a number of properties, such as air permeability index, water absorption rate, water permeability index, chloride diffusivity, electrical resistivity, moisture content and porosity gradient. Most techniques are economical and appropriate for assessing the durability of structures subjected to a single mechanism of deterioration. In reality, structures may face multiple deterioration mechanisms, stress/strains due to both environmental and structural loading and related acceleration of deterioration. Developing an understanding of such multimode deterioration may help in addressing the performance gap between laboratory and field. In this paper, a brief review of some of the ways by which a performance testing strategy could be developed is given so that service life prediction could be more realistic