Anthropogenic activities have drastically altered chemical exposure, with traces of synthetic chemicals detected ubiquitously in the environment. Many of these chemicals are thought to perturb endocrine function, leading to declines in reproductive health and fertility, and increases in the incidence of cancer, metabolic disorders and diabetes. There are over 90 million unique chemicals registered under the Chemical Abstracts Service (CAS), of which only 308,000 were subject to inventory and/or regulation, in September 2013. However, as a specific aim of the EU REACH regulations, the UK is obliged to reduce the chemical safety initiatives reliance on in vivo apical endpoints, promoting the development and validation of alternative mechanistic methods. The human health cost of endocrine disrupting chemical (EDC) exposure in the EU, has been estimated at €31 billion per annum. In light of the EU incentives, this study aims to evaluate current in silico and in vitro tools for EDC screening and hazard characterisation; testing the hypothesis that in silico virtual screening accurately predicts in vitro mechanistic assays. Nuclear receptor binding interactions are the current focus of in silico and in vitro tools to predict EDC mechanisms. To the author’s knowledge, no single study has quantitatively assessed the relationship between in silico nuclear receptor binding and in vitro mechanistic assays, in a comprehensive manner. Tripos ® SYBYL software was used to develop 3D-molecular models of nuclear receptor binding domains. The ligand binding pockets of estrogen (ERα and ERβ), androgen (AR), progesterone (PR) and peroxisome proliferator activated (PPARγ) receptors were successfully modelled from X-ray crystal structures. A database of putative-EDC ligands (n= 378), were computationally ‘docked’ to the pseudo-molecular targets, as a virtual screen for nuclear receptor activity. Relative to in vitro assays, the in silico screen demonstrated a sensitivity of 94.5%. The SYBYL Surflex-Dock method surpassed the OECD Toolbox ER-Profiler, DfW and binary classification models, in correctly identifying endocrine active substances (EAS). Aiming to evaluate the current in vitro tools for endocrine MoA, standardised ERα transactivation (HeLa9903), stably transfected AR transactivation (HeLa4-11) assays in addition to novel transiently transfected reporter gene assays, predicted the mechanism and potency of test substances prioritised from the in silico results (n = 10 potential-EDCs and 10 hormone controls). In conclusion, in silico SYBYL molecular modelling and Surflex-Dock virtual screening sensitively predicted the binding of ERα/β, AR, PR and PPARγ potential EDCs, and was identified as a potentially useful regulatory tool, to support EAS hazard identification.

Thesis advisor: Martin Scanlan / Many district and school leaders have leveraged instructional leadership or social justice leadership to advance student achievement for minoritized students. While research has examined these approaches separately, we identify a potential gap at the nexus between instructional and social justice leadership. In particular, we need further research examining how leaders bridge instructional and social justice leadership practices to disrupt educational inequities. Our study examines how educational leaders weave instructional and social justice leadership skills to cultivate others' social justice pedagogical knowledge and skill. Employing a collective case study framework, this study explores how a mid-sized urban district’s superintendent and school leaders cultivated and promoted the social justice pedagogical knowledge and skill of others. Data was collected through interviews, surveys, and document reviews. The primary research participants included one superintendent, two assistant superintendents, three central office leaders, five school leaders, and six teachers. Our findings highlight four themes: the importance of leaders’ critical self-reflection perceptions of district-level infrastructure and strategic planning, school-level instructional infrastructure and capacity building, and gaps in social justice pedagogical skill. This research has implications for practice, policy, and existing literature related to cultivating and enacting social justice pedagogical knowledge and skill across diverse contexts. / Thesis (EdD) — Boston College, 2024. / Submitted to: Boston College. Lynch School of Education. / Discipline: Educational Leadership and Higher Education.

The diploma thesis Digitization and the Internet - Disruptive Technologies of Television Broadcasting discusses the changes in television forms. Emphasis is placed on the transformation of the market in the form of digitization, which subsequently also led to the intensive distribution of data within the Internet environment. The introductory part of the thesis is arched with theoretical support from the sides of economic and media approaches to the process of change. Their central motif deals with innovation or remediation. A closer description of the technologies themselves and their properties is not omitted either. Thanks to a closer description of the technologies themselves and their properties, it is possible to define the existence of imaginary boundaries of television. The second part of the work focuses specifically on the Czech landscape. It deals with the current state of legislation and the non-linear functions that the Internet has brought to television screens. At the practical level, the thesis focuses on alternative forms of television distribution in the Internet environment. The aim is to present the typical features and innovative elements of the disrupting technology of television broadcasting, which were defined in the theoretical part, on the example of the selected VOD...

Магистерская диссертации посвящена проектированию технологии обучения в целях развития транспрофессиональных компетенций персонала. В теоретической части рассматриваются аспекты проектирования технологии обучения персонала при переходе к тримодальной организации. В практической части описывается общая характеристика исследуемой компании, проводится анализ кадрового состава, а также анализируется HR-бизнес-процесс «Обучение персонала» в ПАО Сбербанк. На основании этих результатов был разработан проект по развитию транспрофессиональных компетенций персонала. / The master's thesis is devoted to the design of training technology for the development of personnel's TRANS-professional competencies. In the theoretical part, the aspects of designing the technology of personnel training in the transition to a trimodal organization are considered. The practical part describes the General characteristics of the company under study, analyzes the personnel structure, and analyzes the HR-business process "personnel Training" in Sberbank. Based on these results, a project was developed to develop the staff's TRANS-professional competencies.