Cellular senescence - its role in cancer and the response to ionizing radiation

© 2011 Sabin and Anderson; licensee BioMed Central Ltd. This article is available through the Brunel Open Access Publishing Fund. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Cellular senescence is a normal biological process that is initiated in response to a range of intrinsic and extrinsic factors that functions to remove irreparable damage and therefore potentially harmful cells, from the proliferative pool. Senescence can therefore be thought of in beneficial terms as a tumour suppressor. In contrast to this, there is a growing body of evidence suggesting that senescence is also associated with the disruption of the tissue microenvironment and development of a pro-oncogenic environment, principally via the secretion of senescence-associated pro-inflammatory factors. The fraction of cells in a senescent state is known to increase with cellular age and from exposure to various stressors including ionising radiation therefore, the implications of the detrimental effects of the senescent phenotype are important to understand within the context of the increasing human exposure to ionising radiation. This review will discuss what is currently understood about senescence, highlighting possible associations between senescence and cancer and, how exposure to ionising radiation may modify this

COMPARISON OF KINEMATICS AND ACCURACY OF OVERHAND AMERICAN FOOTBALL THROWING

This study examined elbow angle, wrist velocity and throwing accuracy during American Football throws. Six repetitions of three types of throws: Self-selected pass (SS), Lob pass (L), and a Bullet pass (B); were performed to hit a point scaled target from 10.97 m. Independent variables were frontal plane shoulder angle (more or less than 90º) and throw type; dependent variables were elbow angle in the sagittal plane, wrist velocity at ball release, and accuracy. There were no differences for shoulder angle for any variable; while throw types differed only for wrist speed (highest to lowest B, SS, and L). Significant interactions occurred for all variables. These findings suggest that recommendations for American football throwing technique are complicated by the combination of throw type and shoulder angle; and that with no restrictions subjects will throw with more accuracy

Subtidal algal community structure in kelp beds around the Cape Peninsula (Western Cape, South Africa)

The subtidal understorey seaweed communities were studied along a coastal distance of 104 km around the Cape Peninsula, which is situated in an overlap region between two marine provinces and characterized by a considerable temperature gradient. Sampling was carried out at six sites (4 to 10 quadrats per site) around the Cape Peninsula. For each of the quadrats, biomass of each species, grazing, and environmental variables such as temperature, wave exposure and sand cover were determined. The data were analysed using canonical correspondence analysis (CCA) and two way indicator species analysis (TWINSPAN). A total of 142 seaweed taxa were found at the six sites (21 Chlorophyta, 14 Phaeophyta and 107 Rhodophyta). The two sides of the Peninsula have a very different biomass-composition of Chlorophyta, Phaeophyta and Rhodophyta. The biomass of Rhodophyta in the Atlantic sites is much higher than in the Bay, and the biomass of Chlorophyta is higher in False Bay than on the west coast. A change in floristic composition of subtidal algal communities around the Cape Peninsula can be observed and is principally related to seawater temperature and wave exposure. Next to these physical factors, grazing is demonstrated to be important in determining species composition. A lower degree of wave exposure might result in a higher number of grazers in False Bay. The occurrence of a higher cover of encrusting corallines in the Bay is probably a consequence of the higher grazing pressure. Distinct community types can be recognized from TWINSPAN and CCA

The collection, linking and use of data in biomedical research and health care: ethical issues

This report takes as its starting point the massive accumulation of data in biomedical research and health care, and the increasing power of data science to extract value by linking and re-using that data, for example in further health or population research. It examines the scientific, policy and economic drivers to exploit these opportunities, and the concerns and potential risks associated with doing so. The faltering ability of conventional information governance measures to keep pace with these developments is identified as a significant problem. The report therefore poses and addresses the following question: "how can we define a set of morally reasonable expectations about the use of data in any given data initiative and what conditions are required to give sufficient confidence that those expectations will be satisfied?" The report sets out a number of general recommendations, including four guiding principles for ethical design and governance of data initiatives. These help to identify specific examples of existing good practice and to make recommendations for improved practice in the use of data in the fields of health care (re-use of NHS records, clinical research, etc.) and population research (biobanks, epidemiological studies, etc.)

The Impact of the Parabolic Dish Concentrator on the Wind Induced Heat Loss From Its Receiver

Abstract To achieve higher operating temperatures, power output and system efficiencies in parabolic dish cavity receivers, larger dish sizes and structures are used to increase the concentration ratio. This increases capital investment and installation costs, which in turn places a much stronger emphasis on accurately predicting the performance of the system and the heat loss from it. Numerous studies have investigated the natural convection heat losses from cavity receivers, and some have examined a cavity exposed to wind. However, the effect of the dish on the wind flow and subsequently the heat loss from the receiver has not been widely considered. In this work, computational fluid dynamics was used to model the flow of air around a parabolic dish concentrator operating at varying angles of operation. The flow fields were validated using wind tunnel testing and published data regarding the aerodynamic characteristics of parabolic dishes. The results showed that the orientation of the dish has a significant effect on the flow structure near the receiver. Subsequently, using the validated method, the convective heat loss from the receiver of a large parabolic dish system was determined for a range of operating conditions. The results support the assertion that the flow characteristics near the cavity receiver aperture depend strongly on the orientation of the dish structure. This resulted in the calculated heat loss being up to 40% lower than previous studies where the presence of the dish was included. As such, the wind flow around the dish needs to be accounted for when analyzing the performance of parabolic dish systems to avoid an overly conservative and hence more expensive design

Molecular signatures of a TLR4 agonist-adjuvanted HIV-1 vaccine candidate in humans

Systems biology approaches have recently provided new insights into the mechanisms of action of human vaccines and adjuvants. Here, we investigated early transcriptional signatures induced in whole blood of healthy subjects following vaccination with a recombinant HIV-1 envelope glycoprotein subunit CN54gp140 adjuvanted with the TLR4 agonist glucopyranosyl lipid adjuvant-aqueous formulation (GLA-AF) and correlated signatures to CN54gp140-specific serum antibody responses. Fourteen healthy volunteers aged 18-45 years were immunized intramuscularly three times at 1-month intervals and whole blood samples were collected at baseline, 6 h, and 1, 3, and 7 days post first immunization. Subtle changes in the transcriptomic profiles were observed following immunization, ranging from over 300 differentially expressed genes (DEGs) at day 1 to nearly 100 DEGs at day 7 following immunization. Functional pathway analysis revealed blood transcription modules (BTMs) related to general cell cycle activation, and innate immune cell activation at early time points, as well as BTMs related to T cells and B cell activation at the later time points post-immunization. Diverse CN54gp140-specific serum antibody responses of the subjects enabled their categorization into high or low responders, at early ( < 1 month) and late (up to 6 months) time points post vaccination. BTM analyses revealed repression of modules enriched in NK cells, and the mitochondrial electron chain, in individuals with high or sustained antigen-specific antibody responses. However, low responders showed an enhancement of BTMs associated with enrichment in myeloid cells and monocytes as well as integrin cell surface interactions. Flow cytometry analysis of peripheral blood mononuclear cells obtained from the subjects revealed an enhanced frequency of CD56 dim NK cells in the majority of vaccines 14 days after vaccination as compared with the baseline. These results emphasize the utility of a systems biology approach to enhance our understanding on the mechanisms of action of TLR4 adjuvanted human vaccines

Determinants of Rolling Stock Maintenance Cost in Metros

This study examines the economies of scale and the determinants of rolling stock maintenance costs for 24 urban rail transit operators. The estimates reveal significant returns to scale in maintenance for both per car and per car kilometre. The econometric analysis also provides statistically significant cost elasticities for wages and staff hours, suggesting substitution effects between factors. Staff outsourcing is found to significantly decrease costs, whereas higher levels of fleet availability at the peak and rolling stock failures increase it. The effect of the age of rolling stock and the network is negligible on rolling stock maintenance costs; however, the analysis reveals a downward trend in rolling stock costs among the metros in the CoMET and Nova consortia

Immunopathogenesis of canine chronic ulcerative stomatitis.

Canine Chronic Ulcerative Stomatitis is a spontaneously occurring inflammatory disease of the oral mucosa. An immune-mediated pathogenesis is suspected though not yet proven. We have recently reported on the clinical and histologic features, and identification of select leukocyte cell populations within the lesion. A clinical and histologic similarity to oral lichen planus of people was proposed. In the present study, these initial observations are extended by examining lesions from 24 dogs with clinical evidence of chronic ulcerative stomatitis. Because dogs with chronic ulcerative stomatitis often have concurrent periodontal disease, we wondered if dental plaque/biofilm may be a common instigator of inflammation in both lesions. We hypothesized that dogs with chronic ulcerative stomatitis would exhibit a spectrum of pathologic changes and phenotype of infiltrating leukocytes that would inform lesion pathogenesis and that these changes would differ from inflammatory phenotypes in periodontitis. Previously we identified chronic ulcerative stomatitis lesions to be rich in FoxP3+ and IL17+ cells. As such, we suspect that these leukocytes play an important role in lesion pathogenesis. The current study confirms the presence of moderate to large numbers of FoxP3+ T cells and IL17+ cells in all ulcerative stomatitis lesions using confocal immunofluorescence. Interestingly, the majority of IL17+ cells were determined to be non-T cells and IL17+ cell frequencies were negatively correlated with severity on the clinical scoring system. Three histologic subtypes of ulcerative stomatitis were determined; lichenoid, deep stomatitis and granulomatous. Periodontitis lesions, like stomatitis lesions, were B cell and plasma cell rich, but otherwise differed from the stomatitis lesions. Direct immunofluorescence results did not support an autoantibody-mediated autoimmune disease process. This investigation contributes to the body of literature regarding leukocyte involvement in canine idiopathic inflammatory disease pathogenesis

Impacts of Unattended Train Operations (UTO) on Productivity and Efficiency in Metropolitan Railways

Urban metro subway systems (metros) around the world are choosing increasing levels of automation for new and existing lines: the global length of metro lines capable of unattended train operation (UTO) is predicted to triple in the next 10 years. Despite significant investment in this technology, empirical evidence for the financial and service quality impacts of UTO in metros remains scarce. This study used questionnaires and semistructured interviews with the Community of Metros and Nova Group benchmarking groups to assemble emerging evidence of how automation affected costs, staffing, service capacity, and reliability. The results from an analysis of data from 23 lines suggested that UTO could reduce staff numbers by 30% to 70%, with the amount of wage cost reduction depending on whether staff on UTO lines were paid more. On the basis of the experience of seven metros, the capital costs of lines capable of UTO were higher, but the internal rate of return had been estimated by two metros at 10% to 15%. Automated lines were capable of operating at the highest service frequencies of up to 42 trains per hour, and the limited available data suggested that automated lines were more reliable. The findings indicated that UTO was a means to a more flexible and reliable operating model that could increase metro productivity and efficiency. The study identified important work needed to understand the impacts of UTO and identify where statistical analyses would add value once sufficiently large data sets became available

What is the impact of acquired immunity on the transmission of schistosomiasis and the efficacy of current and planned mass drug administration programmes?

Schistosomiasis causes severe morbidity in many countries with endemic infection with the schistosome digenean parasites in Africa and Asia. To control and eliminate the disease resulting from infection, regular mass drug administration (MDA) is used, with a focus on school-aged children (SAC; 5-14 years of age). In some high transmission settings, the World Health Organization (WHO) also recommends the inclusion of at-risk adults in MDA treatment programmes. The question of whether ecology (age-dependant exposure) or immunity (resistance to reinfection), or some combination of both, determines the form of observed convex age-intensity profile is still unresolved, but there is a growing body of evidence that the human hosts acquire some partial level of immunity after a long period of repeated exposure to infection. In the majority of past research modelling schistosome transmission and the impact of MDA programmes, the effect of acquired immunity has not been taken into account. Past work has been based on the assumption that age-related contact rates generate convex horizontal age-intensity profiles. In this paper, we use an individual based stochastic model of transmission and MDA impact to explore the effect of acquired immunity in defined MDA programmes. Compared with scenarios with no immunity, we find that acquired immunity makes the MDA programme less effective with a slower decrease in the prevalence of infection. Therefore, the time to achieve morbidity control and elimination as a public health problem is longer than predicted by models with just age-related exposure and no build-up of immunity. The level of impact depends on the baseline prevalence prior to treatment (the magnitude of the basic reproductive number R0) and the treatment frequency, among other factors. We find that immunity has a larger impact within moderate to high transmission settings such that it is very unlikely to achieve morbidity and transmission control employing current MDA programmes