Anti-tumour activity in vitro and in vivo of selective differentiating agents containing hydroxamate

A series of hydroxamates, which are not metalloprotease inhibitors, have been found to be selectively toxic to a range of transformed and human tumour cells without killing normal cells (fibroblasts, melanocytes) at the same concentrations. Within 24 h of treatment, drug action is characterized by morphological reversion of tumour cells to a more normal phenotype (dendritic morphology), and rapid and reversible acetylation of histone H4 in both tumour and normal cells. Two; hydroxamates inhibited growth of xenografts of human melanoma cells in nude mice; resistance did not develop in vivo or in vitro. A third hydroxamate, trichostatin A, was active in vitro but became inactivated and had no anti-tumour activity in vivo. Development of dendritic morphology was found to be dependent upon phosphatase activity, RNA and protein synthesis. Proliferating hybrid clones of sensitive and resistant cells remained sensitive to ABHA, indicating a dominant-negative mechanism of sensitivity. Histone H4 hyperacetylation suggests that these agents act at the chromatin level. This work may lead to new drugs that are potent, and selective anti-tumour agents with low toxicity to normal Cells

The Cyprinodon variegatus genome reveals gene expression changes underlying differences in skull morphology among closely related species

Genes in durophage intersection set at 15 dpf. This is a comma separated table of the genes in the 15 dpf durophage intersection set. Given are edgeR results for each pairwise comparison. Columns indicating whether a gene is included in the intersection set at a threshold of 1.5 or 2 fold are provided. (CSV 13 kb

Factors influencing agreement between child self-report and parent proxy-reports on the Pediatric Quality of Life Inventory™ 4.0 (PedsQL™) generic core scales

BACKGROUND: In situations where children are unable or unwilling to respond for themselves, measurement of quality of life (QOL) is often obtained by parent proxy-report. However the relationship between child self and parent proxy-reports has been shown to be poor in some circumstances. Additionally the most appropriate statistical method for comparing ratings between child and parent proxy-reports has not been clearly established. The objectives of this study were to assess the: 1) agreement between child and parent proxy-reports on an established child QOL measure (the PedsQL™) using two different statistical methods; 2) effect of chronological age and domain type on agreement between children's and parents' reports on the PedsQL™; 3) relationship between parents' own well-being and their ratings of their child's QOL. METHODS: One hundred and forty-nine healthy children (5.5 – 6.5, 6.5 – 7.5, and 7.5 – 8.5 years) completed the PedsQL™. One hundred and three of their parents completed these measures in relation to their child, and a measure of their own QOL (SF-36). RESULTS: Consistency between child and parent proxy-reports on the PedsQL™ was low, with Intra-Class correlation coefficients ranging from 0.02 to 0.23. Correlations were higher for the oldest age group for Total Score and Psychosocial Health domains, and for the Physical Health domain in the youngest age group. Statistically significant median differences were found between child and parent-reports on all subscales of the PedsQL™. The largest median differences were found for the two older age groups. Statistically significant correlations were found between parents' own QOL and their proxy-reports of child QOL across the total sample and within the middle age group. CONCLUSION: Intra-Class correlation coefficients and median difference testing can provide different information on the relationship between parent proxy-reports and child self-reports. Our findings suggest that differences in the levels of parent-child agreement previously reported may be an artefact of the statistical method used. In addition, levels of agreement can be affected by child age, domains investigated, and parents' own QOL. Further studies are needed to establish the optimal predictors of levels of parent-child agreement

Towards emotion recognition for virtual environments: an evaluation of eeg features on benchmark dataset

One of the challenges in virtual environments is the difficulty users have in interacting with these increasingly complex systems. Ultimately, endowing machines with the ability to perceive users emotions will enable a more intuitive and reliable interaction. Consequently, using the electroencephalogram as a bio-signal sensor, the affective state of a user can be modelled and subsequently utilised in order to achieve a system that can recognise and react to the user’s emotions. This paper investigates features extracted from electroencephalogram signals for the purpose of affective state modelling based on Russell’s Circumplex Model. Investigations are presented that aim to provide the foundation for future work in modelling user affect to enhance interaction experience in virtual environments. The DEAP dataset was used within this work, along with a Support Vector Machine and Random Forest, which yielded reasonable classification accuracies for Valence and Arousal using feature vectors based on statistical measurements and band power from the and waves and High Order Crossing of the EEG signal

Non-Invasive Microstructure and Morphology Investigation of the Mouse Lung: Qualitative Description and Quantitative Measurement

BACKGROUND: Early detection of lung cancer is known to improve the chances of successful treatment. However, lungs are soft tissues with complex three-dimensional configuration. Conventional X-ray imaging is based purely on absorption resulting in very low contrast when imaging soft tissues without contrast agents. It is difficult to obtain adequate information of lung lesions from conventional X-ray imaging. METHODS: In this study, a recently emerged imaging technique, in-line X-ray phase contrast imaging (IL-XPCI) was used. This powerful technique enabled high-resolution investigations of soft tissues without contrast agents. We applied IL-XPCI to observe the lungs in an intact mouse for the purpose of defining quantitatively the micro-structures in lung. FINDINGS: The three-dimensional model of the lung was successfully established, which provided an excellent view of lung airways. We highlighted the use of IL-XPCI in the visualization and assessment of alveoli which had rarely been studied in three dimensions (3D). The precise view of individual alveolus was achieved. The morphological parameters, such as diameter and alveolar surface area were measured. These parameters were of great importance in the diagnosis of diseases related to alveolus and alveolar scar. CONCLUSION: Our results indicated that IL-XPCI had the ability to represent complex anatomical structures in lung. This offered a new perspective on the diagnosis of respiratory disease and may guide future work in the study of respiratory mechanism on the alveoli level

Job satisfaction and its modeling among township health center employees: a quantitative study in poor rural China

<p>Abstract</p> <p>Background</p> <p>Job satisfaction is important to staff management of township health centers (THCs), as it is associated with organizational performance, quality of care and employee retention. The purpose of this study was to measure job satisfaction level of THC employees in poor rural China and to identify relevant features in order to provide policy advice on human resource development of health service institutions in poor regions.</p> <p>Methods</p> <p>A self-completion questionnaire was used to assess the job satisfaction and relevant features (response rate: 90.5%) among 172 employees (i.e., clinic doctors, medico-technical workers and public health workers) of 17 THCs in Anhui and Xinjiang provinces of China. The study covered a time period of two months in 2007.</p> <p>Results</p> <p>The mean staff job satisfaction scored 83.3, which was in the category of "somewhat satisfied" on a scale ranging from 0 (extremely dissatisfied) to 100 (extremely satisfied) by employing Likert's transformation formula. Exploratory factor analysis (EFA) revealed eight domains involved in modeling of job satisfaction, among which, the caregivers were more satisfied with job significance (88.2), job competency (87.9) and teamwork (87.7), as compared with work reward (72.9) and working conditions (79.7). Mean job satisfaction in Xinjiang (89.7) was higher than that in Anhui (75.5).</p> <p>Conclusions</p> <p>Employees of THCs have moderate job satisfactions in poor areas, which need to be raised further by improving their working conditions and reward.</p

Characteristic scale of star formation - I. Clump formation efficiency on local scales

We have used the ratio of column densities derived independently from the 850-μm continuum James Clerk Maxwell Telescope Plane Survey and the 13CO/C18O (J = 3 → 2) Heterodyne Inner Milky Way Plane Survey to produce maps of the dense-gas mass fraction (DGMF) in two slices of the Galactic plane centred at ℓ = 30° and 40°. The observed DGMF is a metric for the instantaneous clump formation efficiency (CFE) in the molecular gas. We split the two fields into velocity components corresponding to the spiral arms that cross them, and a two-dimensional power-spectrum analysis of the spiral-arm DGMF maps reveals a break in slope at the approximate size scale of molecular clouds. We interpret this as the characteristic scale of the amplitude of variations in the CFE and a constraint on the dominant mechanism regulating the CFE and, hence, the star formation efficiency in CO-traced clouds

Micro Soft Tissues Visualization Based on X-Ray Phase-Contrast Imaging

The current imaging methods have a limited ability to visualize microstructures of biological soft tissues. Small lesions cannot be detected at the early stage of the disease. Phase contrast imaging (PCI) is a novel non-invasive imaging technique that can provide high contrast images of soft tissues by the use of X-ray phase shift. It is a new choice in terms of non-invasively revealing soft tissue details. In this study, the lung and hepatic fibrosis models of mice and rats were used to investigate the ability of PCI in microstructures observation of soft tissues. Our results demonstrated that different liver fibrosis stages could be distinguished non-invasively by PCI. The three-dimensional morphology of a segment of blood vessel was constructed. Noteworthy, the blood clot inside the vessel was visualized in three dimensions which provided a precise description of vessel stenosis. Furthermore, the whole lung airways including the alveoli were obtained. We had specifically highlighted its use in the visualization and assessment of the alveoli. To our knowledge, this was the first time for non-invasive alveoli imaging using PCI. This finding may offer a new perspective on the diagnosis of respiratory disease. All the results confirmed that PCI will be a valuable tool in biological soft tissues imaging

E17K substitution in AKT1 in prostate cancer

Background:The phosphatidylinositol 3-kinase (PI3K)-AKT pathway is activated in many cancers. Mutational hotspots in AKT1 and in the regulatory and catalytic subunits of PI3K have been detected in multiple tumour types. In AKT1, the E17K substitution leads to a PI3K-independent activation of AKT1.Methods:A mutational profiling of AKT1 and of the mutational hotspots in PIK3CA and PIK3R1 was carried out in samples from primary and recurrent prostate tumours.Results:We show that, in prostate cancer, AKT1(E17K) had a prevalence of 1.4%. The mutation seemed to be associated with a favourable clinical course but it was not associated with a specific tumour growth pattern. Activating mutations in PIK3CA or PIK3R1 were not found in prostate cancer.Conclusion:The E17K substitution in AKT1 is rare in prostate cancer. It seems associated with a favourable clinical outcome but not with a specific histology of the tumo