Educational differentials in cancer mortality and avoidable deaths in Lithuania, 2001–2009: a census-linked study.
Liquid chromatography-tandem mass spectrometry was used to analyze plasma proteins of volunteers (control) and patients with glioblastoma multiform (GBM). A database search was pre-set with a variable post-translational modification (PTM): phosphorylation, acetylation or ubiquitination. There were no significant differences between the control and the GBM groups regarding the number of protein identifications, sequence coverage or number of PTMs. However, in GBM plasma, we unambiguously observed a decreased fraction in post-translationally modified peptides identified with high quality. The disease-specific PTM patterns were extracted and mapped to the set of FDA-approved plasma protein markers. Decreases of 46% and 24% in the number of acetylated and ubiquitinated peptides, respectively, were observed in the GBM samples. Significance of capturing disease-associated patterns of protein modifications was envisaged.
With the advances in the sequencing technology the International Cancer Genome Consortium (ICGC)  and The Cancer Genome Atlas (TCGA)  collected data on more than 16 000 genome-wide pairs tumor-normal tissue providing a valuable resource to study cancer mutations. In this research we focus on pre- evaluation of the relationship between cancer breakpoint hotspots and DNA regions potentially forming secondary structures such as stem-loops (cruciforms) and quadru- plexes. We performed analysis of 2 234 samples covering 10 cancer types and built machine-learning models predicting cancer breakpoint distribution over chromosome based on the density distribution of stem-loops and quadruplexes. We developed pro- cedure for machine learning models building and evaluation as the considered data are extremely imbalanced and it is needed to get reliable estimate of prediction power. We conducted a set of experiments to select the best appropriate resampling scheme, class balancing technique and parameters of machine learning algorithms. The best final models were applied to cancer breakpoints data. From the performed analysis it could be concluded that the relationship between cancer breakpoints hotspots and studied DNA secondary structures exists, however, generally, this relationship is weak for stem-loops, but higher for quadruplexes. We also found differences in model predictive power depending on cancer types. Thus, stem-loop-based model performs better for pancreatic, prostate, ovary, uterus, brain and liver cancer, and quadruplex- based model works better for blood, bone, skin and breast cancer.
Background: Chromosomal rearrangements are the typical phenomena in cancer genomes causing gene disruptions and fusions, corruption of regulatory elements, damage to chromosome integrity. Among the factors contributing to genomic instability are non-B DNA structures with stem-loops and quadruplexes being the most prevalent. We aimed at investigating the impact of specifically these two classes of non-B DNA structures on cancer breakpoint hotspots using machine learning approach.
Methods: We developed procedure for machine learning model building and evaluation as the considered data are extremely imbalanced and it was required to get a reliable estimate of the prediction power. We built logistic regression models predicting cancer breakpoint hotspots based on the densities of stem-loops and quadruplexes, jointly and separately. We also tested Random Forest models varying different resampling schemes (leave-one-out cross validation, train-test split, 3-fold cross-validation) and class balancing techniques (oversampling, stratification, synthetic minority oversampling).
Results: We performed analysis of 487,425 breakpoints from 2234 samples covering 10 cancer types available from the International Cancer Genome Consortium. We showed that distribution of breakpoint hotspots in different types of cancer are not correlated, confirming the heterogeneous nature of cancer. It appeared that stem-loop- based model best explains the blood, brain, liver, and prostate cancer breakpoint hotspot profiles while quadruplex- based model has higher performance for the bone, breast, ovary, pancreatic, and skin cancer. For the overall cancer profile and uterus cancer the joint model shows the highest performance. For particular datasets the constructed models reach high predictive power using just one predictor, and in the majority of the cases, the model built on both predictors does not increase the model performance.
Conclusion: Despite the heterogeneity in breakpoint hotspots’ distribution across different cancer types, our results demonstrate an association between cancer breakpoint hotspots and stem-loops and quadruplexes. Approximately for half of the cancer types stem-loops are the most influential factors while for the others these are quadruplexes. This fact reflects the differences in regulatory potential of stem-loops and quadruplexes at the tissue-specific level, which yet to be discovered at the genome-wide scale. The performed analysis demonstrates that influence of stem- loops and quadruplexes on breakpoint hotspots formation is tissue-specific.
Several approaches to the concept of fatherhood present in Western sociological tradition are analyzed and compared: biological determinism, social constructivism and biosocial theory. The problematics of fatherhood and men’s parental practices is marginalized in modern Russian social research devoted to family and this fact makes the traditional inequality in family relations, when the father’s role is considered secondary compared to that of mother, even stronger. However, in Western critical men’s studies several stages can be outlined: the development of “sex roles” paradigm (biological determinism), the emergence of the hegemonic masculinity concept, inter-disciplinary stage (biosocial theory). According to the approach of biological determinism, the role of a father is that of the patriarch, he continues the family line and serves as a model for his ascendants. Social constructivism looks into man’s functions in the family from the point of view of masculine pressure and establishing hegemony over a woman and children. Biosocial theory aims to unite the biological determinacy of fatherhood with social, cultural and personal context. It is shown that these approaches are directly connected with the level of the society development, marriage and family perceptions, the level of egality of gender order.
This article is talking about state management and cultural policy, their nature and content in term of the new tendency - development of postindustrial society. It mentioned here, that at the moment cultural policy is the base of regional political activity and that regions can get strong competitive advantage if they are able to implement cultural policy successfully. All these trends can produce elements of new economic development.