Modelling radiation-induced cell cycle delays

Ionizing radiation is known to delay the cell cycle progression. In particular after particle exposure significant delays have been observed and it has been shown that the extent of delay affects the expression of damage such as chromosome aberrations. Thus, to predict how cells respond to ionizing radiation and to derive reliable estimates of radiation risks, information about radiation-induced cell cycle perturbations is required. In the present study we describe and apply a method for retrieval of information about the time-course of all cell cycle phases from experimental data on the mitotic index only. We study the progression of mammalian cells through the cell cycle after exposure. The analysis reveals a prolonged block of damaged cells in the G2 phase. Furthermore, by performing an error analysis on simulated data valuable information for the design of experimental studies has been obtained. The analysis showed that the number of cells analyzed in an experimental sample should be at least 100 to obtain a relative error less than 20%.Comment: 19 pages, 11 figures, accepted for publication in Radiation and Environmental Biophysic

Mind-modelling with corpus stylistics in David Copperfield

We suggest an innovative approach to literary discourse by using corpus linguistic methods to address research questions from cognitive poetics. In this article, we focus on the way that readers engage in mind-modelling in the process of characterisation. The article sets out our cognitive poetic model of characterisation that emphasises the continuity between literary characterisation and real-life human relationships. The model also aims to deal with the modelling of the author’s mind in line with the modelling of the minds of fictional characters. Crucially, our approach to mind-modelling is text-driven. Therefore we are able to employ corpus linguistic techniques systematically to identify textual patterns that function as cues triggering character information. In this article, we explore our understanding of mind-modelling through the characterisation of Mr. Dick from David Copperfield by Charles Dickens. Using the CLiC tool (Corpus Linguistics in Cheshire) developed for the exploration of 19th-century fiction, we investigate the textual traces in non-quotations around this character, in order to draw out the techniques of characterisation other than speech presentation. We show that Mr. Dick is a thematically and authorially significant character in the novel, and we move towards a rigorous account of the reader’s modelling of authorial intention

SHIFTING THE PARADIGM IN RADIATION SAFETY

The current radiation safety paradigm using the linear no-threshold (LNT) model is based on the premise that even the smallest amount of radiation may cause mutations increasing the risk of cancer. Autopsy studies have shown that the presence of cancer cells is not a decisive factor in the occurrence of clinical cancer. On the other hand, suppression of immune system more than doubles the cancer risk in organ transplant patients, indicating its key role in keeping occult cancers in check. Low dose radiation (LDR) elevates immune response, and so it may reduce rather than increase the risk of cancer. LNT model pays exclusive attention to DNA damage, which is not a decisive factor, and completely ignores immune system response, which is an important factor, and so is not scientifically justifiable. By not recognizing the importance of the immune system in cancer, and not exploring exercise intervention, the current paradigm may have missed an opportunity to reduce cancer deaths among atomic bomb survivors. Increased antioxidants from LDR may reduce aging-related non-cancer diseases since oxidative damage is implicated in these. A paradigm shift is warranted to reduce further casualties, reduce fear of LDR, and enable investigation of potential beneficial applications of LDR

Seeking and accessing professional support for child anxiety in a community sample

There is a lack of current data on help-seeking, and barriers to accessing professional support for child anxiety disorders. This study aimed to provide current data on the frequency and type of parental help-seeking, professional support received, and parent-reported barriers/facilitators in the context of child anxiety, and to explore factors associated with help-seeking, and parent-reported barriers among help-seekers and non help-seekers. We conducted a survey of help-seeking in parents of 222 children (aged 7-11) with elevated anxiety symptoms identified through screening in schools, 138 children of whom met diagnostic criteria for an anxiety disorder. Almost two-thirds (64.5%) of parents of children with an anxiety disorder reported seeking help from a professional; in 38.4% of cases parents reported that their child had received support from a professional to help manage and overcome their anxiety difficulties, and < 3% had received evidence-based treatment (CBT). Frequently reported parental barriers related to difficulties differentiating between developmentally appropriate and clinically significant anxiety, a lack of help-seeking knowledge, perceived negative consequences of help-seeking, and limited service provision. Non-help seekers were more likely than help seekers to report barriers related to thinking a child's anxiety may improve without professional support, and the absence of professional recognition. Findings identify the need for (i) tools for parents and primary school staff to help identify children who may benefit from professional support to overcome difficulties with anxiety; and (ii) increased evidence-based provision for child anxiety disorders, including delivery within schools and direct support for parents

Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells

The COX-2 protein is frequently overexpressed in human malignant gliomas. This expression has been associated with their aggressive growth characteristics and poor prognosis for patients. Targeting the COX-2 pathway might improve glioma therapy. In this study, the effects of the selective COX-2 inhibitor meloxicam alone and in combination with irradiation were investigated on human glioma cells in vitro. A panel of three glioma cell lines (D384, U87 and U251) was used in the experiments from which U87 cells expressed constitutive COX-2. The response to meloxicam and irradiation (dose-range of 0–6 Gy) was determined by the clonogenic assay, cell proliferation was evaluated by growth analysis and cell cycle distribution by FACS. 24–72 h exposure to 250–750 μM meloxicam resulted in a time and dose dependent growth inhibition with an almost complete inhibition after 24 h for all cell lines. Exposure to 750 μM meloxicam for 24 h increased the fraction of cells in the radiosensitive G2/M cell cycle phase in D384 (18–27%) and U251 (17–41%) cells. 750 μM meloxicam resulted in radiosensitization of D384 (DMF:2.19) and U87 (DMF:1.25) cells, but not U251 cells (DMF:1.08). The selective COX-2 inhibitor meloxicam exerted COX-2 independent growth inhibition and radiosensitization of human glioma cells

More Stable Productivity of Semi Natural Grasslands than Sown Pastures in a Seasonally Dry Climate

In the Neotropics the predominant pathway to intensify productivity is generally thought to be to convert grasslands to sown pastures, mostly in monoculture. This article examines how above-ground net primary productivity (ANPP) in semi-natural grasslands and sown pastures in Central America respond to rainfall by: (i) assessing the relationships between ANPP and accumulated rainfall and indices of rainfall distribution, (ii) evaluating the variability of ANPP between and within seasons, and (iii) estimating the temporal stability of ANPP. We conducted sequential biomass harvests during 12 periods of 22 days and related those to rainfall. There were significant relationships between ANPP and cumulative rainfall in 22-day periods for both vegetation types and a model including a linear and quadratic term explained 74% of the variation in the data. There was also a significant correlation between ANPP and the number of rainfall events for both vegetation types. Sown pastures had higher ANPP increments per unit rainfall and higher ANPP at the peak of the rainy season than semi-natural grasslands. In contrast, semi-natural grasslands showed higher ANPP early in the dry season. The temporal stability of ANPP was higher in semi-natural grasslands than in the sown pastures in the dry season and over a whole annual cycle. Our results reveal that, contrary to conventional thinking amongst pasture scientists, there appears to be no increase in ANPP arising from replacing semi-natural grasslands with sown pastures under prevailing pasture management practices in seasonally dry climates, while the temporal distribution of ANPP is more even in semi-natural grasslands. Neither sown pastures nor semi-natural grasslands are productive towards the end of the dry season, indicating the potential importance of the widespread practice of retaining tree cover in pastures

NK105, a paclitaxel-incorporating micellar nanoparticle, is a more potent radiosensitising agent compared to free paclitaxel

NK105 is a micellar nanoparticle formulation designed to enhance the delivery of paclitaxel (PTX) to solid tumours. It has been reported to exert antitumour activity in vivo and to have reduced neurotoxicity as compared to that of free PTX. The purpose of this study was to investigate the radiosensitising effect of NK105 in comparison with that of PTX. Lewis lung carcinoma (LLC)-bearing mice were administered a single intravenous (i.v.) injection of PTX or NK105; 24 h after the drug administration, a proportion of the mice received radiation to the tumour site or lung fields. Then, the antitumour activity and lung toxicity were evaluated. In one subset of mice, the tumours were excised and specimens were prepared for analysis of the cell cycle distribution by flow cytometry. Combined NK105 treatment with radiation yielded significant superior antitumour activity as compared to combined PTX treatment with radiation (P=0.0277). On the other hand, a histopathological study of lung sections revealed no significant difference in histopathological changes between mice treated with PTX and radiation and those treated with NK105 and radiation. Flow-cytometric analysis showed that NK105-treated LLC tumour cells showed more severe arrest at the G2/M phase as compared to PTX-treated tumour cells. The superior radiosensitising activity of NK105 was thus considered to be attributable to the more severe cell cycle arrest at the G2/M phase induced by NK105 as compared to that induced by free PTX. The present study results suggest that further clinical trials are warranted to determine the efficacy and feasibility of combined NK105 therapy with radiation