Miracle-dz/UniFAR-FTUs huggingface dataset:
BRUCE regulates DNA double-strand break response by promoting USP8 deubiquitination of BRIT1

Significance DNA damage response is essential to preserve genomic stability. Here we report a previously unknown function for the baculovirus inhibitor of apoptosis protein repeat (BIR)-containing ubiquitin-conjugating enzyme (BRUCE) and ubiquitin-specific peptidase 8 (USP8) as activators of DNA damage response. They drive recruitment of the breast cancer susceptibility gene C terminus-repeat inhibitor of human telomerase reverse transcriptase expression (BRIT1) to DNA breaks by promoting BRIT1 deubiquitination. In contrast to the established regulation of repair foci formation by ubiquitination, our data demonstrate deubiquitination as a previously unrecognized critical step in promoting foci formation. Furthermore, we define a pathway by which BRUCE and USP8 activate BRIT1–switch/sucrose nonfermentable (SWI-SNF)–mediated chromatin relaxation to maximize cell responsiveness to DNA damage. Thus, BRUCE represents a novel component in safeguarding genomic stability and a promising therapeutic target in diseases of genomic instability such as cancer. The DNA damage response (DDR) is crucial for genomic integrity. BRIT1 (breast cancer susceptibility gene C terminus-repeat inhibitor of human telomerase repeat transcriptase expression), a tumor suppressor and early DDR factor, is recruited to DNA double-strand breaks (DSBs) by phosphorylated H2A histone family, member X (γ-H2AX), where it promotes chromatin relaxation by recruiting the switch/sucrose nonfermentable (SWI–SNF) chromatin remodeler to facilitate DDR. However, regulation of BRIT1 recruitment is not fully understood. The baculovirus IAP repeat (BIR)-containing ubiquitin-conjugating enzyme (BRUCE) is an inhibitor of apoptosis protein (IAP). Here, we report a non-IAP function of BRUCE in the regulation of the BRIT1–SWI–SNF DSB-response pathway and genomic stability. We demonstrate that BRIT1 is K63 ubiquitinated in unstimulated cells and that deubiquitination of BRIT1 is a prerequisite for its recruitment to DSB sites by γ-H2AX. We show mechanistically that BRUCE acts as a scaffold, bridging the ubiquitin-specific peptidase 8 (USP8) and BRIT1 in a complex to coordinate USP8-catalyzed deubiquitination of BRIT1. Loss of BRUCE or USP8 impairs BRIT1 deubiquitination, BRIT1 binding with γ-H2AX, the formation of BRIT1 DNA damage foci, and chromatin relaxation. Moreover, BRUCE-depleted cells display reduced homologous recombination repair, and BRUCE-mutant mice exhibit repair defects and genomic instability. These findings identify BRUCE and USP8 as two hitherto uncharacterized critical DDR regulators and uncover a deubiquitination regulation of BRIT1 assembly at damaged chromatin for efficient DDR and genomic stability.
Mapping invariance in the ventral occipital temporal pathway

This thesis is concerned with the organisation of the human ventral occipital temporal pathway, part of the brain involved in the recognition of objects and processing of scenes. The architecture of this system has been extensively investigated with functional magnetic resonance imaging (fMRI) which reveals the engagement of parts of the brain in different tasks. Conventional analyses have been used to identify discrete, circumscribed brain regions which appear to be specialised for processing particular categories of stimuli, such as faces or landscapes. In characterising the function of these regions, an important factor in previous research has been to establish whether or not they are invariant to more basic sensory properties such as size or 3D orientation, which change as places and objects are encountered from different points of view. A more recent suggestion is that the ventral occipital temporal pathway, rather than being comprised of discrete regions, is better conceived of as a continuous topographical map, or multiple overlapping maps. Within this framework, fundamental computational requirements, such as the need to establish different forms of invariance, may provide overarching organising principles governing the spatial arrangement of processing within ventral visual cortex. This more nuanced view of the functional architecture of the visual system demands a more nuanced view of invariance. Through a series of experiments using fMRI in conjunction with a parametric adaptation paradigm, this thesis investigates the invariance of neural representations as a continuous variable that can be explicitly quantified rather than an all-or-none phenomenon. This novel approach reveals structure and symmetry normally hidden in conventional analyses. Invariance is found to vary by degree throughout the ventral surface of the brain depending on the nature of the stimulus and the types of processing required. Different forms of invariance can be dissociated from one another in terms of distinct spatial patterns of parametric adaptation that different forms of visual change generate.
Teacher‐involved conversations with young children during small group activity

This qualitative study examines the conversations of two preschool teachers with two‐ and three‐year‐old children during small‐group activity settings in two high‐quality child development centers. Using interviews, observations and videotaping of small‐group activities, the conversations are characterized in terms of the kind and function of language, the usage of cognitive demands and the reciprocal nature of these conversations. The findings indicate that teachers use declarative statements primarily to manage instruction and encourage language development. While teachers control most conversations, teacher–child reciprocity is evident and more genuine in authentic, teacher‐guided activities. In both classrooms, the language during small‐group activities is characterized as having low cognitive demands. Teachers and teacher educators need to be more cognizant of their language, including its purpose and opportunities to facilitate cognitively challenging conversations with young children. Recommendations for practice are provided.
Assessing the Moral Relevance of Peace Education Contents in the Basic Education Social Studies Curricula for Effective Citizenship Participation in Nigeria

Social Studies is a core subject at the basic education level in Nigeria which has the potentials of inculcating functional knowledge and desirable morals into pupils for effective citizenship participation through peaceful co-existence. However, despite this positive trend, the moral significance of peace education contents of the subject seem not to have been adequately explored. This lacuna justified the need for this study which sought to find out the moral relevance of peace education contents in basic education social studies in Nigerian schools. The study adopted a descriptive survey design with content analysis bias. A sample of 200 social studies teachers undergoing in-service sandwich training were selected through stratified random sampling technique from states across the six geo-political zones of Nigeria. Three research questions guided the study. Similarly, two major instruments namely 10-item questionnaire titled “Teachers’ Awareness of the Moral Relevance of Peace Education Contents in Basic Education Social Studies Curriculum” and content analysis of the same social studies curricula published by NERDC, a foremost Nigerian educational regulatory body were used for data collection. Data collected were analyzed with the use of arithematic percentages. Findings of the study showed that majority of the teachers were not only aware of the moral relevance of peace education contents in basic education social studies curricula but were also of the opinion that the subject could be used to meet the moral and peace education needs of Nigerian pupils for the purpose of inclusion citizenship participation. It was also established that peace and moral education contents were adequately reflected in the basic education social studies curricula. These findings were exhaustively discussed with far-reaching recommendations on how to improve the teaching and learning of moral aspects of peace education contents through the basic education social studies curricula for effective promotion of inclusive citizenship participation in a multi-ethnic and religious society like Nigeria. Keywords: Basic Education, Moral, Moral Relevance, Social Studies Curricula, Citizenship Participation.
USING AN ANALYTIC NETWORK PROCESS MODEL IN COMBINATORIAL AUCTIONS

Auctions are important market mechanisms for the allocation of goods and services. Auctions are preferred often to other common processes because they are open, quite fair, easiness to understand by participants, and lead to economically efficient outcomes. Design of auctions is a multidisciplinary effort made of contributions from economics, operations research, informatics, and other disciplines. Combinatorial auctions are those auctions in which bidders can place bids on combinations of items, called packages, rather than just individual items. The advantage of combinatorial auctions is that the bidder can more fully express his preferences. This is particular important when items are complements. The multiple evaluation criteria can be used. There are dependencies among sellers, buyers, criteria, bundles of items. A variety of feedback processes creates complex system of items. For the whole structure seems to be very appropriate Analytic Network Process (ANP) approach. The ANP method makes possible to deal systematically with all kinds of dependence and feedback in the system of items. By the ANP approach can be evaluated the preferences of bundles of items. Dynamic Network Process (DNP) as an extension of ANP can deal with time dependent priorities in combinatorial auctions. http://dx.doi. org/10.13033/ijahp.v1i2. 47
NeuA Sialic Acid O-Acetylesterase Activity Modulates O-Acetylation of Capsular Polysaccharide in Group B Streptococcus*

Group B Streptococcus (GBS) is a common cause of neonatal sepsis and meningitis. A major GBS virulence determinant is its sialic acid (Sia)-capped capsular polysaccharide. Recently, we discovered the presence and genetic basis of capsular Sia O-acetylation in GBS. We now characterize a GBS Sia O-acetylesterase that modulates the degree of GBS surface O-acetylation. The GBS Sia O-acetylesterase operates cooperatively with the GBS CMP-Sia synthetase, both part of a single polypeptide encoded by the neuA gene. NeuA de-O-acetylation of free 9-O-acetyl-N-acetylneuraminic acid (Neu5,9Ac2) was enhanced by CTP and Mg2+, the substrate and co-factor, respectively, of the N-terminal GBS CMP-Sia synthetase domain. In contrast, the homologous bifunctional NeuA esterase from Escherichia coli K1 did not display cofactor dependence. Further analyses showed that in vitro, GBS NeuA can operate via two alternate enzymatic pathways: de-O-acetylation of Neu5,9Ac2 followed by CMP activation of Neu5Ac or activation of Neu5,9Ac2 followed by de-O-acetylation of CMP-Neu5,9Ac2. Consistent with in vitro esterase assays, genetic deletion of GBS neuA led to accumulation of intracellular O-acetylated Sias, and overexpression of GBS NeuA reduced O-acetylation of Sias on the bacterial surface. Site-directed mutagenesis of conserved asparagine residue 301 abolished esterase activity but preserved CMP-Sia synthetase activity, as evidenced by hyper-O-acetylation of capsular polysaccharide Sias on GBS expressing only the N301A NeuA allele. These studies demonstrate a novel mechanism regulating the extent of capsular Sia O-acetylation in intact bacteria and provide a genetic strategy for manipulating GBS O-acetylation in order to explore the role of this modification in GBS pathogenesis and immunogenicity.
SOCIAL CAPITAL AS A CATALYST FOR COMMUNITY DEVELOPMENT: A CASE OF POOR LOCALITIES IN ADDIS ABABA, ETHIOPIA

Social capital has enjoyed an impressive growth across the social sciences over the last two decades. It has been particularly prominent across development studies. The study investigates social capital and human and economic variations in poor localities and its influence on the capacity of community for development. The relationship between social capital dimensions and human and economic characteristics of the households with community development has been analysed using multivariate analysis based on data collected from 497 households in poor localities of Addis Ababa. Community development is highly associated with increased participation in local associations; trust in the community, confidence in local institutions and pattern of reciprocity among inhabitants in the locality. These findings provide qualified support for the systemic model of local social organization but challenge theory of social disorganization that predicts lower levels of social capital in poor communities.
1 . 2 Sample Application Scenario

Content-based retrieval has become a very popular and also powerful paradigm for searching in multimedia collections, especially in large collections of images. However, such queries require that one or even several reference images are available prior to the start of the search process. These reference images must be close to the final result so that the user can take them to express her information need. If such reference images are not available or if the information need is covered only by parts of the query object, the result usually does not meet the user’s expectation. Therefore, more flexible user interfaces are needed that allow users to sketch a query image by hand drawings and to dynamically select regions of interest from a given query image. In this paper, we present a novel approach to query by sketch where interactive paper and image similarity search are seamlessly combined. It is based on the iPaper/iServer system of ETH Zurich and the ISIS/OSIRIS content-based image retrieval system of the University of Basel. The paper presents the integrated system which has already very successfully been applied to the development of an interactive museum catalogue. Moreover, it reports on ongoing activities that aim at extending the system to support handwritten sketches, gestures and/or dynamic region selection to make the retrieval process more flexible and less dependent from existing query objects.
Dimensions of Service Quality in Hotels in Accra, Ghana

Customers have expectations at every level of their interaction with a business whether face-to-face, over the phone, on the internet or by post. To meet and/or exceed these expectations, businesses need to know and understand what their customers expect from them so that they can deliver services to satisfy their customers. This study examined the dimensions of hotel guests’ expectations of service quality and the relative impact of the dimensions in influencing the overall level of service quality. Questionnaires were used to collect data from hotel guests in Accra. The results indicate that four underlying factors influenced guests’ expectations of service quality and among these four factors three were found to be significant in predicting expectations. The results provide insights and suggestions for change in hotel management practices.
Using MDA to develop Component and Aspect Based Applications

Distributed systems are complex and, consequently, their design and development is not an easy task. In order to manage such complexity, it is not enough the use of the appropriate software technologies. Additionally, software developers need to differentiate clearly the several concepts used at different levels of the development (application domain, application architecture, implementation language and platform, etc.). This paper proposes the use of MDA in the development of CAM/DAOP applications, where CAM/DAOP is a component-aspect model and platform that we have developed for the construction of distributed applications. The main goal of this paper is to describe the process we followed to identify and separate the entities that live at different levels, and the transformations among them.
Transient arrest in a quiescent state allows ovarian cancer cells to survive suboptimal growth conditions and is mediated by both Mirk/dyrk1b and p130/Rb2

Some ovarian cancer cells in vivo are in a reversible quiescent state where they can contribute to cancer spread under favorable growth conditions. The serine/threonine kinase Mirk/dyrk1B was expressed in each of seven ovarian cancer cell lines and in 21 of 28 resected human ovarian cancers, and upregulated in 60% of the cancers. Some ovarian cancer cells were found in a G0 quiescent state, with the highest fraction in a line with an amplified Mirk gene. Suboptimal culture conditions increased the G0 fraction in SKOV3 and TOV21G, but not OVCAR4 cultures. Less than half as many OVCAR4 cells survived under suboptimal culture conditions as shown by total cell numbers, dye exclusion viability studies, and assay of cleaved apoptotic marker proteins. G0 arrest in TOV21G and SKOV3 cells led to increased levels of Mirk, the CDK inhibitor p27, p130/Rb2, and p130/Rb2 complexed with E2F4. The G0 arrest was transient, and cells exited G0 when fresh nutrients were supplied. Depletion of p130/Rb2 reduced the G0 fraction, increased cell sensitivity to serum‐free culture and to cisplatin, and reduced Mirk levels. Mirk contributed to G0 arrest by destabilization of cyclin D1. In TOV21G cells, but not in normal diploid fibroblasts, Mirk depletion led to increased apoptosis and loss of viability. Because Mirk is expressed at low levels in most normal adult tissues, the elevated Mirk protein levels in ovarian cancers may present a novel therapeutic target, in particular for quiescent tumor cells which are difficult to eradicate by conventional therapies targeting dividing cells.
Enhancement of the Controlled-Release Properties of Chitosan Membranes by Crosslinking with Suberoyl Chloride

A novel crosslinking agent, suberoyl chloride, was used to crosslink N-phthaloyl acylated chitosan and improves the properties of chitosan membranes. Membranes with different crosslinking degrees were synthesized. The derivatives were characterized by Fourier transform infrared spectroscopy and 13C solid state nuclear magnetic resonance spectroscopy, which indicated that the crosslinking degrees ranged from 0 to 7.4%. The permeabilities of various plant nutrients, including macroelements (N, P, K), microelements (Zn2+ and Cu2+), and a plant growth regulator (naphthylacetic acid), were varied by moderate changes in crosslinking degree, indicating that the controlled-release properties can be regulated in this way. The film-forming ability of native chitosan was maintained, whilst mechanical properties, hydrophobicity and controlled permeability were improved. These dramatic improvements occurred with a small amount of added suberoyl chloride; excessive crosslinking led to membranes with unwanted poor permeability. Thus, both the mechanical properties and permeability of the crosslinked membrane can be optimized.
Variability of Home Blood Pressure Measurements Between First and Second Measurements on One Occasion, and Factors Related to Variability

The number of home blood pressure (BP) measurements on one occasion has continued to be discussed. Therefore, we evaluated the variability of the first and second measurements on one occasion. The subjects except hypertensive patients (393 males, 212 females; mean age 38.7 y) were recruited from one company. Home blood pressure was measured with a semiautomatic device, and subjects were instructed to perform triplicate morning and evening measurements on 7 consecutive days. The standard deviation of systolic blood pressure (SBP) was significantly greater in the first measurement than in the second measurement, but there was no significant difference in standard deviation of diastolic blood pressure. As for the coefficient of variation (CV), CV of morning SBP alone was significantly greater in the first measurement (5.3% ± 0.1%) than in the second measurement (4.9% ± 0.1%). Therefore, factors related to CV of morning SBP in the first measurement were studied, which indicated that it was significantly greater in smokers (5.8% ± 0.1%) than in nonsmokers (5.2% ± 0.1%), and in women (5.6% ± 0.1%) than in men (5.2% ± 0.1%). In conclusion, CV of morning SBP was significantly greater in the first measurement than in the second measurement. The coefficient of variation of morning SBP in the first measurement might be influenced to some extent by the presence or absence of smoking habit and gender. Therefore, physicians should pay special attention to the above-mentioned fact in the future.
Estonia 1989-2000: enormous increase in mortality differences by education.

BACKGROUND Having regained its political autonomy in 1991, Estonia experienced major changes in political, economic, and social realities. We aimed to analyse mortality changes by education from 1989 to 2000 in order to assess the impact of recent changes in Estonia, as well as the delayed effects of pre-transitional developments. METHODS Two census-based analyses were compared. Individual cause-specific death data for those aged 20+ for 1987-1990 (72 003 deaths) and 1999-2000 (35 477 deaths) came from the national mortality database. Population denominators came from the population censuses of 1989 and 2000. Mortality for all causes combined and for selected causes of death were analysed for high, mid, and low educational groups. The absolute differences in mortality were evaluated through life expectancy at age 25 and age-standardized mortality rates. To assess the relative differences between educational levels, mortality rate ratios with 95% CI were calculated using Poisson regression. RESULTS Educational differences in mortality increased tremendously from 1989 to 2000: over the 10-year period life expectancy improved considerably for graduates, and worsened for those with the lowest education. In 2000, male graduates aged 25 could expect to live 13.1 years longer than corresponding men with the lowest education; among women the difference was 8.6 years. Large differences were observed in all selected causes of death in 1989 and in 2000 and the trends were invariably much more favourable for the higher educated. Educational differences in total mortality increased in all age groups. CONCLUSIONS Social disruption and increasing inequalities in wealth can be considered main recent determinants; however, causal processes, shaped decades before recent reforms, also contribute to this widening gap.
Optimal multi-content video decomposition for efficient video transmission over low-bandwidth networks

In this paper, an interactive framework for navigating video sequences over Internet protocol (IP)-based networks is presented using an optimal content-based video decomposition scheme. In particular, each video sequence is analyzed at different "content resolution levels", creating a hierarchy from the lowest (coarse) to the highest (fine) resolution. This content hierarchy is represented as a tree structure, each level of which corresponds to a particular content resolution, while the tree-nodes indicate the regions that the sequence content is partitioned at a given resolution. Optimal content-based video decomposition is performed by minimizing a cross correlation criterion so that the most representative shots from a video sequence or frames from a video shot are extracted. Experimental results on real-life video sequences show a sufficient representation of the visual content at each resolution level and a significant reduction of the transmission information, compared to the traditional sequential video scanning.