Prodrug strategies of antiviral nucleotides: Studies on enzymatically and thermally removable phosphate protecting groups

Antiviral nucleosides are compounds that are used against viruses, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV). To act as therapeutic agent, the antiviral nucleoside needs to be phosphorylated to nucleotide in the body in three consecutive phosphorylation steps by cellular or viral enzymes. The first phosphorylation to the nucleoside monophosphate is often inefficient and leads to poor antiviral activity. The antiviral efficacy can be improved by applying a prodrug strategy and delivering the antiviral nucleoside directly as its monophosphate. In prodrug strategies of antiviral nucleotides, the negative charges on the phosphate moiety are temporarily masked with protecting groups. Once inside the cell, the protecting groups are removed by enzymatic or chemical processes. Many prodrug strategies apply biodegradable protecting groups, the removal of which is triggered by esterase enzymes. Several studies have, however, demonstrated that the removal rate of the second and subsequent esterase labile protecting groups significantly slows down after the first protecting group is removed due to the negative charge on the phosphodiester intermediate, which disturbs the catalytic site of the enzyme. In this thesis, esterase labile protecting group strategies where the issue of retardation could be avoided were studied. Prodrug candidates of antiviral nucleotides were synthesized and kinetic studies on the chemical and enzymatic stability were carried out. In the synthesized compounds, the second protecting group is cleaved from the monophosphate some other mechanism than esterase triggered activation or the structure of prodrug requires only one protecting group. In addition, esterase labile protecting group which is additionally thermally removable was studied. This protecting group was cleaved from oligomeric phosphodiesters both enzymatically and thermally and seems most attractive of the studied phosphate protecting groups. However, the rate of the thermal removal still is too slow to allow efficient protection of longer oligonucleotides and needs optimization. Key words: antiviral, nucleotide, prodrug, protecting group, biodegradable

Socially shared metacognitive regulation during collaborative learning processes in student dyads and small groups

Traditionally metacognition has been theorised, methodologically studied and empirically tested from the standpoint mainly of individuals and their learning contexts. In this dissertation the emergence of metacognition is analysed more broadly. The aim of the dissertation was to explore socially shared metacognitive regulation (SSMR) as part of collaborative learning processes taking place in student dyads and small learning groups. The specific aims were to extend the concept of individual metacognition to SSMR, to develop methods to capture and analyse SSMR and to validate the usefulness of the concept of SSMR in two different learning contexts; in face-to-face student dyads solving mathematical word problems and also in small groups taking part in inquiry-based science learning in an asynchronous computer-supported collaborative learning (CSCL) environment. This dissertation is comprised of four studies. In Study I, the main aim was to explore if and how metacognition emerges during problem solving in student dyads and then to develop a method for analysing the social level of awareness, monitoring, and regulatory processes emerging during the problem solving. Two dyads comprised of 10-year-old students who were high-achieving especially in mathematical word problem solving and reading comprehension were involved in the study. An in-depth case analysis was conducted. Data consisted of over 16 (30–45 minutes) videotaped and transcribed face-to-face sessions. The dyads solved altogether 151 mathematical word problems of different difficulty levels in a game-format learning environment. The interaction flowchart was used in the analysis to uncover socially shared metacognition. Interviews (also stimulated recall interviews) were conducted in order to obtain further information about socially shared metacognition. The findings showed the emergence of metacognition in a collaborative learning context in a way that cannot solely be explained by individual conception. The concept of socially-shared metacognition (SSMR) was proposed. The results highlighted the emergence of socially shared metacognition specifically in problems where dyads encountered challenges. Small verbal and nonverbal signals between students also triggered the emergence of socially shared metacognition. Additionally, one dyad implemented a system whereby they shared metacognitive regulation based on their strengths in learning. Overall, the findings suggested that in order to discover patterns of socially shared metacognition, it is important to investigate metacognition over time. However, it was concluded that more research on socially shared metacognition, from larger data sets, is needed. These findings formed the basis of the second study. In Study II, the specific aim was to investigate whether socially shared metacognition can be reliably identified from a large dataset of collaborative face-to-face mathematical word problem solving sessions by student dyads. We specifically examined different difficulty levels of tasks as well as the function and focus of socially shared metacognition. Furthermore, the presence of observable metacognitive experiences at the beginning of socially shared metacognition was explored. Four dyads participated in the study. Each dyad was comprised of high-achieving 10-year-old students, ranked in the top 11% of their fourth grade peers (n=393). Dyads were from the same data set as in Study I. The dyads worked face-to-face in a computer-supported, game-format learning environment. Problem-solving processes for 251 tasks at three difficulty levels taking place during 56 (30–45 minutes) lessons were video-taped and analysed. Baseline data for this study were 14 675 turns of transcribed verbal and nonverbal behaviours observed in four study dyads. The micro-level analysis illustrated how participants moved between different channels of communication (individual and interpersonal). The unit of analysis was a set of turns, referred to as an ‘episode’. The results indicated that socially shared metacognition and its function and focus, as well as the appearance of metacognitive experiences can be defined in a reliable way from a larger data set by independent coders. A comparison of the different difficulty levels of the problems suggested that in order to trigger socially shared metacognition in small groups, the problems should be more difficult, as opposed to moderately difficult or easy. Although socially shared metacognition was found in collaborative face-to-face problem solving among high-achieving student dyads, more research is needed in different contexts. This consideration created the basis of the research on socially shared metacognition in Studies III and IV. In Study III, the aim was to expand the research on SSMR from face-to-face mathematical problem solving in student dyads to inquiry-based science learning among small groups in an asynchronous computer-supported collaborative learning (CSCL) environment. The specific aims were to investigate SSMR’s evolvement and functions in a CSCL environment and to explore how SSMR emerges at different phases of the inquiry process. Finally, individual student participation in SSMR during the process was studied. An in-depth explanatory case study of one small group of four girls aged 12 years was carried out. The girls attended a class that has an entrance examination and conducts a language-enriched curriculum. The small group solved complex science problems in an asynchronous CSCL environment, participating in research-like processes of inquiry during 22 lessons (á 45–minute). Students’ network discussion were recorded in written notes (N=640) which were used as study data. A set of notes, referred to here as a ‘thread’, was used as the unit of analysis. The inter-coder agreement was regarded as substantial. The results indicated that SSMR emerges in a small group’s asynchronous CSCL inquiry process in the science domain. Hence, the results of Study III were in line with the previous Study I and Study II and revealed that metacognition cannot be reduced to the individual level alone. The findings also confirm that SSMR should be examined as a process, since SSMR can evolve during different phases and that different SSMR threads overlapped and intertwined. Although the classification of SSMR’s functions was applicable in the context of CSCL in a small group, the dominant function was different in the asynchronous CSCL inquiry in the small group in a science activity than in mathematical word problem solving among student dyads (Study II). Further, the use of different analytical methods provided complementary findings about students’ participation in SSMR. The findings suggest that it is not enough to code just a single written note or simply to examine who has the largest number of notes in the SSMR thread but also to examine the connections between the notes. As the findings of the present study are based on an in-depth analysis of a single small group, further cases were examined in Study IV, as well as looking at the SSMR’s focus, which was also studied in a face-to-face context. In Study IV, the general aim was to investigate the emergence of SSMR with a larger data set from an asynchronous CSCL inquiry process in small student groups carrying out science activities. The specific aims were to study the emergence of SSMR in the different phases of the process, students’ participation in SSMR, and the relation of SSMR’s focus to the quality of outcomes, which was not explored in previous studies. The participants were 12-year-old students from the same class as in Study III. Five small groups consisting of four students and one of five students (N=25) were involved in the study. The small groups solved ill-defined science problems in an asynchronous CSCL environment, participating in research-like processes of inquiry over a total period of 22 hours. Written notes (N=4088) detailed the network discussions of the small groups and these constituted the study data. With these notes, SSMR threads were explored. As in Study III, the thread was used as the unit of analysis. In total, 332 notes were classified as forming 41 SSMR threads. Inter-coder agreement was assessed by three coders in the different phases of the analysis and found to be reliable. Multiple methods of analysis were used. Results showed that SSMR emerged in all the asynchronous CSCL inquiry processes in the small groups. However, the findings did not reveal any significantly changing trend in the emergence of SSMR during the process. As a main trend, the number of notes included in SSMR threads differed significantly in different phases of the process and small groups differed from each other. Although student participation was seen as highly dispersed between the students, there were differences between students and small groups. Furthermore, the findings indicated that the amount of SSMR during the process or participation structure did not explain the differences in the quality of outcomes for the groups. Rather, when SSMRs were focused on understanding and procedural matters, it was associated with achieving high quality learning outcomes. In turn, when SSMRs were focused on incidental and procedural matters, it was associated with low level learning outcomes. Hence, the findings imply that the focus of any emerging SSMR is crucial to the quality of the learning outcomes. Moreover, the findings encourage the use of multiple research methods for studying SSMR. In total, the four studies convincingly indicate that a phenomenon of socially shared metacognitive regulation also exists. This means that it was possible to define the concept of SSMR theoretically, to investigate it methodologically and to validate it empirically in two different learning contexts across dyads and small groups. In-depth micro-level case analysis in Studies I and III showed the possibility to capture and analyse in detail SSMR during the collaborative process, while in Studies II and IV, the analysis validated the emergence of SSMR in larger data sets. Hence, validation was tested both between two environments and within the same environments with further cases. As a part of this dissertation, SSMR’s detailed functions and foci were revealed. Moreover, the findings showed the important role of observable metacognitive experiences as the starting point of SSMRs. It was apparent that problems dealt with by the groups should be rather difficult if SSMR is to be made clearly visible. Further, individual students’ participation was found to differ between students and groups. The multiple research methods employed revealed supplementary findings regarding SSMR. Finally, when SSMR was focused on understanding and procedural matters, this was seen to lead to higher quality learning outcomes. Socially shared metacognition regulation should therefore be taken into consideration in students’ collaborative learning at school similarly to how an individual’s metacognition is taken into account in individual learning.

Comparative antiproliferation of human prostate cancer cells by ethanolic extracts of two groups of Brazilian propolis

Two groups of propolis, group 12, which was collected in the southeastern Brazil and group 13, which was collected in the northeastern Brazil, were examined for antiproliferation of primary malignant tumor (RC-58T/h/SA#4)-derived human prostate cancer cells and human prostate epithelial cells. The strongest inhibition of RC-58T/h/SA#4 cells was observed in propolis group 13 extracts, whereas moderate growth inhibition was observed in human prostate epithelial cells in comparison with group 12. It can be said that the Brazilian propolis of group 13 contains important chemical ingredients.

Catalogue Of the main groups of Ephemera Collection

The Ephemera Collection has been organised in groups based on the topic. The collection also includes groups formed on the basis of the publication type.

Collective learning within nursing clinical groups /

This qualitative study examined collective learning within nursing clinical groups. Specifically, it explored the influence of the individual on the group and the impact of the group on the individual. The study was organized using the concepts from Debbie Kilgore's theory of collective learning (1999). The sample consisted of 1 8 second-year university nursing students and 3 clinical instructors. Data were collected via individual interviews with each participant and researcher's observations during a group conference. The interviews were tape-recorded, transcribed, and analyzed using key concepts from Kilgore's framework. Several interesting findings emerged. Overall, it appeared that individual components and group components contributed to the quality and quantity of collective learning that occurred in the groups. Individually, each person's past group experiences, personality, culture, and gender influenced how that individual acted in the group, their roles, and how much influence they had over group decisions. Moreover, the situation which seemed to cause the greatest sense of helplessness and loss of control was when one of their group members was breaking a norm. They were unable to deal with such situations constructively. Also, the amount of sense of worthiness (respect) and sense of agency (control) the member felt within the group had an impact on the person's role in group decisions. Finally, it seemed that students felt more connected with their peers within the clinical setting when they were close with them on a personal and social level. With respect to the group elements, it seemed that the instructors' values and way of being were instrumental in shaping the group's identity. In group 2, there were clear examples of group consciousness and the students' need to go along with the majority viewpoint, even when it was contrary to their own beliefs. Finally, the common goal of passing clinical and dealing with the fears of being in the clinical setting brought solidarity among the group members, and there seemed to be a high level of positive interdependence among them. From the discussion and analysis of the findings, recommendations were given on how to improve the learning within clinical groups.

Exploring the experiences of male spousal caregivers for their wives with alzheimer disease in their homes : the lived experience and the men's perception of support groups /

This research is qualitative in nature and has explored, by means of interviews, the '^^ experiences of 10 men in their roles in caring for their spouses with Alzheimer Disease (see glossary) in their homes. Additional data were collected by attending 3 formal support group meetings and one informal meeting of a group of men who brought their wives to a support group meeting for their wives with AD. The data retrieved supported the assumption that education about the disease, utilization of formal community support services, and attendance at caregiver support groups or programs can assist healthy male caregivers in caring for their wives with AD in their homes.

Self-presentational motives in eating disorders : a known groups difference approach

Self-presentation reflects the processes by which individuals attempt to monitor and control the impressions others form of them (Schlenker & Leary, 1982). Concerns over impressions conveyed have been linked to numerous health behaviors (Crawford & Eklund, 1994; Martin, Leary, & O'Brien, 2001). The present study investigated the role of cognitive manifestations of dispositional and situational self presentational motivation (SPM) in 131 females with known groups differences on a measure of eating disorders. Participants were classified as in-treatment (IN = 39); at risk (AT = 46); and not at risk (NOT = 46) for eating disordered behaviour. Each participant completed The Brief Fear of Negative Evaluation Scale (FNE; Leary, 1983), the Public Self-Consciousness Scale (PSC; Fenigstein, Sheier, & Buss, 1975), and the Social Physique Anxiety Scale (SPA; Hart, Leary, & Rejeski, 1989), as measures of dispositional SPM. Situational SPM was assessed through Self-Presentational Efficacy (SPE; Gammage, Hall, & Martin, 2004), and the Exercise Motivation Inventory-2 (Markland & Ingeldew, 1997). Significant differences emerged on the measure of eating disorder behaviour between AT and NOT. To determine if group differences existed on measures of trait SPM an ANOVA was conducted. Results indicated that the NOT group experienced less FNE, PSC and SPA than the IN and AT groups, and the AT group experienced less FNE and PSC than the IN group. Pearson bivariate correlations were conducted on measures of trait SPM and EMI-2 subscales theoretically linked to SPM. It was found that FNE, PSC and SPA were all positively correlated with weight management for the NOT group. To determine if group differences existed on selfpresentational exercise motives independent samples I-tests were conducted. Results revealed that the AT group was more motivated to exercise for weight management, and appearance, and social recognition than the NOT group. To determine if group differences existed on the state measure of self-presentational efficacy a series of ANOVA's were conducted. Results revealed that the NOT group experienced significantly greater self-presentational efficacy expectancy and self-presentational outcome value than the AT group. Finally, a discriminant function analysis was conducted to determine if trait SPM would predict group membership. Results revealed that 63.4% of participants were correctly classified, with SPA, PSC, and FNE differentiating the NOT group from the AT and IN groups and FNE and PSC differentiating the AT group from the IN group. Thus self-presentation motivation appears to have an influence on females who have an eating disorder and those at risk for an eating disorder. Potential applications of the influence of self-presentational motives on eating disorders and future research directions are discussed.

Zero-sum problems in finite cyclic groups

The purpose of this thesis is to investigate some open problems in the area of combinatorial number theory referred to as zero-sum theory. A zero-sequence in a finite cyclic group G is said to have the basic property if it is equivalent under group automorphism to one which has sum precisely IGI when this sum is viewed as an integer. This thesis investigates two major problems, the first of which is referred to as the basic pair problem. This problem seeks to determine conditions for which every zero-sequence of a given length in a finite abelian group has the basic property. We resolve an open problem regarding basic pairs in cyclic groups by demonstrating that every sequence of length four in Zp has the basic property, and we conjecture on the complete solution of this problem. The second problem is a 1988 conjecture of Kleitman and Lemke, part of which claims that every sequence of length n in Zn has a subsequence with the basic property. If one considers the special case where n is an odd integer we believe this conjecture to hold true. We verify this is the case for all prime integers less than 40, and all odd integers less than 26. In addition, we resolve the Kleitman-Lemke conjecture for general n in the negative. That is, we demonstrate a sequence in any finite abelian group isomorphic to Z2p (for p ~ 11 a prime) containing no subsequence with the basic property. These results, as well as the results found along the way, contribute to many other problems in zero-sum theory.

The Influence of the Media on Shaping Perceptions of Leadership in Sport: A Within and Between Groups Design

An experimental design that included both between-group and within-group designs was used to assess media influence on perceptions of sport leadership. Participants were recruited and randomly assigned to three groups, where each group completed two separate survey sessions regarding leader personality traits and behaviours. During the second survey session, experimental Groups 1 and 2 watched a video on a separate, respective sport leader prior to filling out the survey. There were a total of 104 participants (N = 104) for the first session, and 99 (N = 99) participants completed the second session. One-way ANOVA, factorial repeated measures ANOVA, and ANCOVA were used for data analysis. Results indicate a significant change in Group 2’s results after watching the video clip, thus rejecting the null hypotheses. Results and implications are discussed, highlighting their relationships to sport and media related theories and sport management practice.

Influence of functional groups of activated carbon in the anchoring of iron particles by forced hydrolysis and its use to remove hexavalent chromiun from aqueous solutions.

Tesis (Master of Science with orientation in Sustainable Processes) UANL, 2014.

Reference Groups and Individual Deprivation

We provide an axiomatization of Yitzhaki’s index of individual deprivation. Our result differs from an earlier characterization due to Ebert and Moyes in the way the reference group of an individual is represented in the model. Ebert and Moyes require the index to be defined for all logically possible reference groups, whereas we employ the standard definition of the reference group as the set of all agents in a society. As a consequence of this modification, some of the axioms used by Ebert and Moyes can no longer be applied and we provide alternative formulations.

Blood, fire and fertility : human remains and ritual practices at the temple pyramid groups of Cantona, Puebla, Mexico

La ville préhispanique de Cantona, située dans la vallée d’Oriental dans l’état de Puebla au Mexique, atteignit sa première apogée culturelle entre 150 av. J.C. et 600/650 A.D. Durant cette période, des complexes cérémoniaux comprenant des groupes de pyramides-temples et des terrains de jeu de balle furent construits. Ces installations servirent au déroulement de nombreux rites au cours desquels les victimes de sacrifices étaient décapitées, démembrées, décharnées, écorchées, bouillies, brûlées et, dans certains cas, consommées. D’autres traitements du corps humain comportent l’inhumation d’individus en position assise et repliés sur eux-mêmes. Pour mieux comprendre le traitement mortuaire rituel des corps humains à Cantona, les découvertes faites sur place sont comparées aux données datant de la même époque obtenues dans trois régions voisines : la vallée de Mexico, Puebla-Tlaxcala et le golfe du Mexique. A partir de ces renseignements, on peut en déduire que la majorité des découvertes faites à Cantona sont les restes des dépouilles et offrandes provenant de rites destinés à la communication avec les dieux et à l’obtention de la fertilité, tandis que les dépouilles des individus en position assise appartiennent à des prêtres ou à des personnages religieux.