Statistical Analysis of Data on Linker Histones/DNA Interactions

2000 Mathematics Subject Classification: 62P10, 92C40Linker histones (H1, H1o H5, subtypes and variants) play a pivotal role in formation of higher order chromatin structure and thus - as main regulators of the expression of genetic information kept in DNA. That is why the knowledge of the nature of linker histones/DNA interactions is of a greatest interest in understanding of such important issues as transcription regulation, cell division, and cancerogenesis. As DNA is a main "target" of most anticancer antibiotics, the analysis of competitive reactions between that drugs (in our case actinomycin D and netropsin) and linker histones for binding to certain sites in DNA gives hopeful information concerning the mode of such interactions. In this work we present statistical analysis of some experimental data concerning the influence of some anticancer antibiotics on linker histones/DNA interactions. First, it was investigated the formulated hypothesis of the dependence of H1/DNA interaction on actinomycin D concentration. Such a relation was expected knowing the different mode for binding of the both drugs to DNA double helix. The applied statistical analysis using chi-square test for independence showed that the concentration of Actinomycin D in reaction mixture had no essential effect on linker histone/DNA binding. On the contrary, the same analysis with the second antibiotic - netropsin showed that we could not reject the hypothesis of dependence. Some other statistical models are also proposed, applying chi-square test for homogeneity, test of Willcockson, Smirnov's test and others.This paper is supported by NESI - Bulgaria - Grant K - 1003/2000 Partialy supported by Pro-ENBIS GTC1 -2001-43031. This paper is supported by NESI - Bulgaria - Grant MM - 1101/2001

Drug Mass Transfer Mechanism, Thermodynamics, and In Vitro Release Kinetics of Antioxidant-encapsulated Zeolite Microparticles as a Drug Carrier System

The aim of the present study was to develop a new vitamin E-zeolite drug carrier system, and investigate the mass transfer mechanism of the antioxidant encapsulation and release on/from the mineral matrix by thermodynamic and kinetics sorption/desorption experiments and mathematical modelling of the experimental data. The surface, morphological and spectral characteristics of the vitamin and the zeolite were determined by Boehm titration, SEM, FTIR and UV/Vis spectrophotometric analyses. Intraparticle diffusion was not the only rate-limiting mechanism, as the mixed-order kinetics model gave the highest regression coefficient (R2) and lowest SSE, MSE, RMSE, and AICC values. The thermodynamic study confirmed the endothermic nature of the spontaneous encapsulation process and increased degrees of randomness at the solid-liquid interface. The in vitro release results were best modelled by the zero-order and sigmoidal models. The results obtained are essential for the development of innovative vitamin E-carrier systems for application in human and veterinary medicine

Materialising architecture for social care: brick walls and compromises in design for later life.

This article reports on an ethnography of architectural projects for later life social care in the UK. Informed by recent debates in material studies and ‘materialities of care’ we offer an analysis of a care home project that is sensitive to architectural materials that are not normally associated with care and wellbeing. Although the care home design project we focus on in this article was never built, we found that design discussions relating to both a curved brick wall and bricks more generally were significant to its architectural ‘making’. The curved wall and the bricks were used by the architects to encode quality and values of care into their design. This was explicit in the design narrative that was core to a successful tender submitted by a consortium comprising architects, developers, contractors, and a care provider to a local authority who commissioned the care home. However, as the project developed, initial consensus for the design features fractured. Using a materialised analysis, we document the tussles generated by the curved wall and the bricks and argue that mundane building materials can be important to, and yet marginalised within, the relations inherent within an ‘architectural care assemblage.’ During the design process we saw how decisions about materials are contentious and they act as a catalyst of negotiations that compromise ‘materialities of care.

AN ANALYSIS OF STUDENT SATISFACTION WITH THE ORGANIZATION OF HYBRID TEACHING IN THE DEPARTMENT OF HEALTH ECONOMICS

The PURPOSE of this research is for a survey to be conducted among the students of the Faculty of Public Health “Prof. Tzekomir Vodenicharov, МD, DSc” at Medical University – Sofia to study whether they are satisfied with how hybrid teaching has been organized in the Department of Health Economics. MATERIALS AND METHODS: An anonymous questionnaire survey was conducted. Out of all students who were invited to participate, 309 joined. The questionnaire was distributed through the Google Forms platform from June to October 2022. Chi-Quadrant analysis was used in order to find relationships between categorical variables. RESULTS: the result shows a statistically significant connection between the students who are studying different specialties in the FPH and their satisfaction with the organization of the hybrid classes carried out by the Department (p <0.001). From the participants’ responses, it is clear that the implementation of hybrid form of teaching (in-person classes for practical training and online classes for theoretical study) carried out through open educational resources and implementing innovative teaching methodology is preferred by the students. CONCLUSION: The scientific evidence arising from our empirical research can aid in the development of guidelines for practical improvement of the hybrid teaching organization in disciplines taught in the Department. The conclusions drawn presuppose continuous research with proper methodologies applied

POSIWID and determinism in design for behaviour change

Copyright @ 2012 Social Services Research GroupWhen designing to influence behaviour for social or environmental benefit, does designers' intent matter? Or are the effects on behaviour more important, regardless of the intent involved? This brief paper explores -- in the context of design for behaviour change -- some treatments of design, intentionality, purpose and responsibility from a variety of fields, including Stafford Beer's "The purpose of a system is what it does" and Maurice Broady's perspective on determinism. The paper attempts to extract useful implications for designers working on behaviour-related problems, in terms of analytical or reflective questions to ask during the design process

A Comparative Approach Linking Molecular Dynamics of Altered Peptide Ligands and MHC with In Vivo Immune Responses

The recognition of peptide in the context of MHC by T lymphocytes is a critical step in the initiation of an adaptive immune response. However, the molecular nature of the interaction between peptide and MHC and how it influences T cell responsiveness is not fully understood.We analyzed the immunological consequences of the interaction of MHC class II (I-Au) restricted 11-mer peptides of myelin basic protein with amino acid substitutions at position 4. These mutant peptides differ in MHC binding affinity, CD4+ T cell priming, and alter the severity of peptide-induced experimental allergic encephalomyelitis. Using molecular dynamics, a computational method of quantifying intrinsic movements of proteins at high resolution, we investigated conformational changes in MHC upon peptide binding. We found that irrespective of peptide binding affinity, MHC deformation appears to influence costimulation, which then leads to effective T cell priming and disease induction. Although this study compares in vivo and molecular dynamics results for three altered peptide ligands, further investigation with similar complexes is essential to determine whether spatial rearrangement of peptide-MHC and costimulatory complexes is an additional level of T cell regulation

Why Map Issues? On Controversy Analysis as a Digital Method

This paper takes stock of recent efforts to implement controversy analysis as a digital method, in the study of science, technology and society (STS) and beyond, and outlines a distinctive approach to addressing a key challenge: the problem of digital bias. Digital media technologies exert significant influence on the enactment of controversy in online settings, and this risks to undermine the substantive focus of controversy analysis conducted by digital means. To address this problem, I propose a shift in thematic focus from controversy analysis to issue mapping. The paper begins by distinguishing between three broad frameworks that currently guide the development of controversy analysis as a digital method: demarcationist, discursive and empiricist. While each of these frameworks has been adopted in STS, I argue that the last one offers the best opportunities to further develop its distinctive approach to controversy analysis and address the problem of digital bias: this last framework allows us to digitally implement the “move beyond impartiality” in the study of knowledge, technology and society. To clarify how, I distinguish between two opposing solutions to the problem of digital bias in controversy analysis: a precautionary approach that seeks to render controversy independent from digital platforms, and an affirmative approach, which deploys specifically digital formats such as hyperlinks and hashtags to map controversies. Endorsing the latter approach, I argue that it needs to be developed further in order to secure the substantive focus of digital controversy analysis. We must broaden the scope of digital controversy analysis and examine not just controversies, but a broader range of issue formations, including public relations campaigns and activist mobilizations. I explore the practical implementation of this approach by discussing a pilot study in which we analyzed issues of Internet governance with the social media platform Twitter

Networks, interfaces and computer-generated images: Learning from digital visualisations of urban redevelopment projects

Over the past five years, computer-generated images (CGIs) have become commonplace as a means to market urban redevelopments. To date, however, they have been given relatively little attention as a new form of visualising the urban. In this paper we argue that these CGIs deserve more attention, and attention of a particular kind. We argue that, instead of approaching them as images situated in urban space, their digitality invites us to understand them as interfaces circulating through a software-supported network space. We use an actor-network theory understanding of ‘network’ and argue that the action done on and with CGIs as they are created takes place at a series of interfaces. These interfaces—between and among humans, software, and hardware—are where work is done both to create the CGI and to create the conditions for their circulation. These claims are explored in relation to the CGIs made for a large urban redevelopment project in Doha, Qatar. We conclude by suggesting that geographers need to reconsider their understanding of digital images and be as attentive to the interfaces embedded in the image as to the CGI’s visual content.The project was funded by a grant from the Economic and Social Research Council RES-062-23-3305

Characterization of Structural Features Controlling the Receptiveness of Empty Class II MHC Molecules

MHC class II molecules (MHC II) play a pivotal role in the cell-surface presentation of antigens for surveillance by T cells. Antigen loading takes place inside the cell in endosomal compartments and loss of the peptide ligand rapidly leads to the formation of a non-receptive state of the MHC molecule. Non-receptiveness hinders the efficient loading of new antigens onto the empty MHC II. However, the mechanisms driving the formation of the peptide inaccessible state are not well understood. Here, a combined approach of experimental site-directed mutagenesis and computational modeling is used to reveal structural features underlying “non-receptiveness.” Molecular dynamics simulations of the human MHC II HLA-DR1 suggest a straightening of the α-helix of the β1 domain during the transition from the open to the non-receptive state. The movement is mostly confined to a hinge region conserved in all known MHC molecules. This shift causes a narrowing of the two helices flanking the binding site and results in a closure, which is further stabilized by the formation of a critical hydrogen bond between residues αQ9 and βN82. Mutagenesis experiments confirmed that replacement of either one of the two residues by alanine renders the protein highly susceptible. Notably, loading enhancement was also observed when the mutated MHC II molecules were expressed on the surface of fibroblast cells. Altogether, structural features underlying the non-receptive state of empty HLA-DR1 identified by theoretical means and experiments revealed highly conserved residues critically involved in the receptiveness of MHC II. The atomic details of rearrangements of the peptide-binding groove upon peptide loss provide insight into structure and dynamics of empty MHC II molecules and may foster rational approaches to interfere with non-receptiveness. Manipulation of peptide loading efficiency for improved peptide vaccination strategies could be one of the applications profiting from the structural knowledge provided by this study