Em Algorithm for MLE of a Probit Model for Multiple Ordinal Outcomes

The correlated probit model is frequently used for multiple ordered data since it allows to incorporate seamlessly different correlation structures. The estimation of the probit model parameters based on direct maximization of the limited information maximum likelihood is a numerically intensive procedure. We propose an extension of the EM algorithm for obtaining maximum likelihood estimates for a correlated probit model for multiple ordinal outcomes. The algorithm is implemented in the free software environment for statistical computing and graphics R. We present two simulation studies to examine the performance of the developed algorithm. We apply the model to data on 121 women with cervical or endometrial cancer. Patients developed normal tissue reactions as a result of post-operative external beam pelvic radiotherapy. In this work we focused on modeling the effects of a genetic factor on early skin and early urogenital tissue reactions and on assessing the strength of association between the two types of reactions. We established that there was an association between skin reactions and polymorphism XRCC3 codon 241 (C>T) (rs861539) and that skin and urogenital reactions were positively correlated. ACM Computing Classification System (1998): G.3

Analysis of Signaling Endosome Composition and Dynamics Using SILAC in Embryonic Stem Cell-Derived Neurons

Neurons require efficient transport mechanisms such as fast axonal transport to ensure neuronal homeostasis and survival. Neurotrophins and their receptors are conveyed via fast axonal retrograde transport of signaling endosomes to the soma, where they elicit transcriptional responses. Despite the essential roles of signaling endosomes in neuronal differentiation and survival, little is known about their molecular identity, dynamics, and regulation. Gaining a better mechanistic understanding of these organelles and their kinetics is crucial, given the growing evidence linking vesicular trafficking deficits to neurodegeneration. Here, we exploited an affinity purification strategy using the binding fragment of tetanus neurotoxin (HCT) conjugated to monocrystalline iron oxide nanoparticles (MIONs), which in motor neurons, is transported in the same carriers as neurotrophins and their receptors. To quantitatively assess the molecular composition of HCT-containing signaling endosomes, we have developed a protocol for triple Stable Isotope Labeling with Amino acids in Cell culture (SILAC) in embryonic stem cell-derived motor neurons. After HCT internalization, retrograde carriers were magnetically isolated at different time points and subjected to mass-spectrometry and Gene Ontology analyses. This purification strategy is highly specific, as confirmed by the presence of essential regulators of fast axonal transport in the make-up of these organelles. Our results indicate that signaling endosomes undergo a rapid maturation with the acquisition of late endosome markers following a specific time-dependent kinetics. Strikingly, signaling endosomes are specifically enriched in proteins known to be involved in neurodegenerative diseases and neuroinfection. Moreover, we highlighted the presence of novel components, whose precise temporal recruitment on signaling endosomes might be essential for proper sorting and/or transport of these organelles. This study provides the first quantitative proteomic analysis of signaling endosomes isolated from motor neurons and allows the assembly of a functional map of these axonal carriers involved in long-range neuronal signaling

L1 transfer in the acquisition of English articles. Evidence from L1 Bulgarian and L1 Norwegian learners

This study investigates the L1 transfer in the acquisition of articles in L2 English by L1 speakers of Bulgarian and Norwegian. Bulgarian differs from English in that it has no overt indefinite article, the definite article is postposed, and it expresses genericity by means of the definite article. Norwegian is similar to English in that it has overt indefinite article. The definite article in Norwegian is postposed and genericity is expressed by both definite, indefinite, singular and plural, and in that Norwegian is similar to both Bulgarian and English. The study consists of a Grammaticality judgement test (GJT) administered to Bulgarian students in grade 6/7 aged 12-13 (N=234), and Norwegian students in grade 6/7 aged 11-12 (N=134). A Proficiency placement test was administered before the GJT in order to match the groups for proficiency level. Six sub-conditions were differentiated, two of which targeted the use of the indefinite article. For both of them, the results showed a large difference in the number of correct answers between L1 Norwegian students and L1 Bulgarian students. The difference is largest in the condition where Norwegian requires an obligatory indefinite article. In the condition where Norwegian requires a bare noun, the difference between the two language groups is smaller. In all other sub-conditions, there is no difference between the two language groups. The results confirm that L1 influences the acquisition of articles in L2 English

Periodization of Creative Self-Realization

People are sensitive in communication and they undergo relationship problems. They are influenced by others’ evaluation striving for adequate personal self-realization. A periodization of personal creative self-realization is presented, based on psychosexual developmental stages and psychosocial developmental stages for achievement of personal growth and life goals. The proposed periodization of creative self-realization comprises nine stages - Pre-natal stage (from conception to birth); Stage of creative longing (from new-born to 1 year and 7 months); Creative verbal stage (from 1 year and 7 months to 2 years and 7 months); Stage of creative and innovative attitudes (from 2 years and 7 months to 6 years); Stage of creative and innovative self-determination (from 6 years to 11 years); Stage of choice of creative self-realization (from 11 years to 19 years); Inspired creative self-realization stage (from 19 years to 24 years); Stage of conscious intentional creative self-realization (from 24 years to 33 years); and Stage of satisfying creative self-realization (after 33 years)

Cyclin D mediates tolerance of genome-doubling in cancers with functional p53

BACKGROUND: Aneuploidy and chromosomal instability (CIN) are common features of human malignancy that fuel genetic heterogeneity. Although tolerance to tetraploidization, an intermediate state that further exacerbates CIN, is frequently mediated by TP53 dysfunction, we find that some genome-doubled tumours retain wild-type TP53. We sought to understand how tetraploid cells with a functional p53/p21-axis tolerate genome-doubling events. METHOD: We performed quantitative proteomics in a diploid/tetraploid pair within a system of multiple independently derived TP53 wild-type tetraploid clones arising spontaneously from a diploid progenitor. We characterized adapted and acute tetraploidization in a variety of flow cytometry and biochemical assays and tested our findings against human tumours through bioinformatics analysis of the TCGA dataset. RESULTS: Cyclin D1 was found to be specifically overexpressed in early but not late passage tetraploid clones, and this overexpression was sufficient to promote tolerance to spontaneous and pharmacologically induced tetraploidy. We provide evidence that this role extends to D-type cyclins and their overexpression confers specific proliferative advantage to tetraploid cells. We demonstrate that tetraploid clones exhibit elevated levels of functional p53 and p21 but override the p53/p21 checkpoint by elevated expression of cyclin D1, via a stoichiometry-dependent and CDK activity-independent mechanism. Tetraploid cells do not exhibit increased sensitivity to abemaciclib, suggesting that cyclin D-overexpressing tumours might not be specifically amenable to treatment with CDK4/6 inhibitors. CONCLUSION: Our study suggests that D-type cyclin overexpression is an acute event, permissive for rapid adaptation to a genome-doubled state in TP53 wild-type tumours and that its overexpression is dispensable in later stages of tumour progression

NEED AND EXPECTATIONS FOR LEARNING IN A STEM ENVIRONMENT

In the last decade, the need for specialists in the field of engineering and exact sciences emerged in Bulgaria and around the world. This led to the launch of a National Program for the construction of stem centers in schools. From the Veliko Tarnovo region, 16 schools joined the program at different stages, where STEM centers are being built or are already functioning in various subjects, which significantly support the preparation of quality personnel for the Bulgarian economy. A review and analysis of the expectations of teachers and students from work in centers with an engineering focus and training in natural sciences was made. At the next stage, an analysis and evaluation of the effect of the implementation of these innovative centers will be done.

BREEDING OF SUNFLOWER (HELIANTHUS ANNUUS L.) AT DOBRUDZHA AGRICULTURAL INSTITUTE – GENERAL TOSHEVO

Dobrudzha Agricultural Institute – General Toshevo is the only breeding center of sunflower in Bulgaria. Since its establishement in 1951, over 50 varieties and hybrids of this crop have been developed here. More than 15 joint hybrids have been registered abroad, the result from cooperation with our European partners. The institute has a rich and variable collection of initial breeding materials. The methods we use in our breeding work are intraspecific, interlinear, interspecific and intergeneric hybridization, experimental mutagenesis, embryoculture, somaclonal variation, in vitro screening and selection. The methods for evaluation of resistance to economically important diseases and the parasite Orobanche have been adapted to the working conditions of the Institute. Morphological, biological, technological, biochemical and phytopathological characterizations of the released and registered hybrids and their parental lines have been made. Many new materials have been developed during the last decade, which possess valuable breeding properties. Over 6000 inbred lines are involved in the breeding work. Annually, 1400 new hybrid combinations are being tested in Bulgaria and abroad. Hybrids have been developed, which possess very good productivity and adaptability potential, and which have been registered in Bulgaria, EU and other foreign contries. Some foreign companies included our new hybrids (Velko, Veleka, Yana, Divna, Valin, etc.) in their catalogs and are successfully organizing their seed production and marketing in the respective countries. A new direction of our breeding is the devlopment of sunflower hybrids resistant to herbicides. Several hybrids - Enigma, Sunny imi, Desi, Viyani, Danaya, etc., are now within the system of official testing in Bulgaria and abroad. Their registration is forthcoming. The aim of this investigation was to present the current status and achievements of the breeding work on sunflower at DAI-General Toshevo during the last decade

IMPACT OF TYPES OF ELECTROMAGNETIC RADIATION ON LIVING NATURE

In our daily life we are exposed to electromagnetic radiation in a very wide range. In our century, these radiations are constantly increasing, and we do not always know how to protect ourselves from them and how they affect people and the rest of living nature. An attempt has been made to analyze the impact of emissions from a different frequency spectrum - from power supply with a frequency of 50 Hertz to high-frequency mobile communications with a frequency of up to 300 GHz. Studies in countries of Europe and the world were taken as a basis, and a study was made about the impact of these electromagnetic radiations in Central Northern Bulgaria and the Veliko Tarnovo region. It is shown how morbidity changes when they affect the peripheral and central nervous systems of people and what effect they can cause at high powers and high intensity at short distances.

Local and Overall Similarities in Educational Design

Abstract Increased rate of exam failure in mathematics is observed at many educational institutions in the last years. Various approaches have been applied to resolve that problem. Some of them like e-learning methodologies and intelligent tutoring systems are more technologically oriented while others focus on face to face communications and group study techniques. In this work we consider a way to adjust teaching set up by involving students' recommendations and requests in the educational design. Increased rate of exam failure in mathematics is observed at many educational institutions in the last years. Various approaches have been applied to resolve that problem. Some of them like e-learning methodologies and intelligent tutoring systems are more technologically oriented while others focus on face to face communications and group study techniques. In this work we consider a way to adjust teaching set up by involving students' recommendations and requests in the educational design