INVESTIGATION OF ANTICOAGULATION PROPERTIES OF SULFATED GLYCOSAMINOGLYCAN MIMETICS

Abstract INVESTEGATION OF ANTICOAGULATION PROPERTIES OF SULFATED GLYCOSAMINOGLYCAN MIMETICS By Elsamani Ismail Abdelfadiel, MS A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University Virginia Commonwealth University, 2017. Supervisor: Umesh R Desai Professor, Department of Medicinal Chemistry The existence of thrombosis in numerous pathophysiological situations formed a vast necessity for anticoagulation therapy. Thrombin and factor Xa are the only two factors of the entire coagulation cascade that have been major targets for regulation of clotting via the direct and indirect mechanism of inhibition. Our recent discovery of sulfated non-saccharide glycosaminoglycan mimetics, especially G2.2, that demonstrates highly selective cancer stem-like cells (CSCs) inhibition activity. G2.2 inhibited the growth of CSCs from multiple cancer cell lines. To evaluate its in vivo anticoagulation effect, we asked a contract research organization (CRO) to produce 20 g of material, labelled as G2.2Y. Evaluation of G2.2C in HT-29 xenograft mouse model showed a significant reduction in tumor volume and CSC markers, but unexpected bleeding consequences in some animals were observed. Also in a tail bleeding experiment, G2.2Y showed a significant enhancement in bleeding volume. Comparable studies with G2.2 synthesized in our laboratory had shown no bleeding effects. To investigate the difference between the two G2.2 samples (G2.2W (white) and G2.2Y (Yellow) that were performed using UPLC-MS characterization, we were able to determine that the G2.2Y sample was an 85:15 blend of two compounds. Elemental, NMR and MS data revealed that G2.2W was fully sulfated flavonoid derivative, as expected, but G2.2Y contained one less sulfate group. We tested both agents for their inhibition of various coagulation factors and revealed that G2.2Y inhibited fXIa nearly 2-fold better in comparison to G2.2W. Furthermore, activated partial thromboplastin time assay (APTT) indicated that G2.2W exhibited almost 3-4-fold less anticoagulant activity compared to G2.2Y. This indicates that the loss of just one sulfate group could induce substantial side effects and lead to a discovery of new anticoagulant agent. Such structure–activity relationship is important to understand if the in vivo metabolism of the agents leads to accumulation of de-sulfated products

Preface Volume 63

AbstractThis volume contains the Proceedings of the First Workshop on Security of Mobile Multiagent Systems (SEMAS'2001). The Workshop was held in Montreal, Canada on May 29, 2001, as satellite event to the 5th International Conference on Autonomous Agents 2001The far reaching influence of the Internet has resulted in an increased interest in agent technologies, which are poised to play a key role in the implementation of successful Internet and WWW-based applications in the future. While there is still considerable hype concerning agent technologies, there is also an increasing awareness of the problems involved. Although there is a large body of work on cryptographic techniques that provide basic building-blocks to solve specific security problems, relatively little work has been done in investigating security in the multiagent system context. The introduction of mobile software agents significantly increases the risks involved in Internet and WWW-based applications. The aim of this workshop was to bring together people from the two relevant research fields, software security and agent-oriented programming. This volume covers actual research papers on security protocols and security policies to enforce security of mobile or multiagent systems but also introduces ideas how to use mobile agents to ensure security of a distributed system.The papers in this volume were reviewed by the program committee consisting, besides editor, of Sahin Albayrak(Technical University Berlin)David Basin(Department of Computer Science, University of Freiburg)Ciaran Bryce(University of Geneve)Hans-Juergen Buerckert(German Research Center for Artificial Intelligence, DFKI)Guenther Karjoth(IBM Research Zuerich)Luc Moreau(Department of Computer Science, University of Southhampton)Volker Roth(Fraunhofer Gesellschaft IGD, Darmstadt)Helmut Schwigon(Bundesamt fuer Sicherheit in der Informationstechnik, BonnVipin Swarup(The MITRE Corp., Boston)Christian Tschudin(Uppsala University)Jan Vitek(Purdue University)This volume will be published as volume 63 in the series Electronic Notes in Theoretical Computer Science (ENTCS). This series is published electronically through the facilities of Elsevier Science B.V. and its auspices. The volumes in the ENTCS series can be accessed at the URL http://www.elsevier.nl/locate/entcsWe are very grateful to the following persons, whose help has been crucial for the success of CMCS'2000: Adele E. Howe, for her help with the organization of the Workshop as satellite event of AA'2001 and Mike Mislove, one of the Managing Editors of the ENTCS series, for his assistance with the use of the ENTCS style files.December 15, 2001 Dieter Hutte

Large-scale network organization in the avian forebrain: a connectivity matrix and theoretical analysis

Many species of birds, including pigeons, possess demonstrable cognitive capacities, and some are capable of cognitive feats matching those of apes. Since mammalian cortex is laminar while the avian telencephalon is nucleated, it is natural to ask whether the brains of these two cognitively capable taxa, despite their apparent anatomical dissimilarities, might exhibit common principles of organisation on some level. Complementing recent investigations of macro-scale brain connectivity in mammals, including humans and macaques, we here present the first large-scale wiring diagram for the forebrain of a bird. Using graph theory, we show that the pigeon telencephalon is organised along similar lines to that of a mammal. Both are modular, small-world networks with a connective core of hub nodes that includes prefrontal-like and hippocampal structures. These hub nodes are, topologically speaking, the most central regions of the pigeon's brain, as well as being the most richly connected, implying a crucial role in information flow. Overall, our analysis suggests that indeed, despite the absence of cortical layers and close to 300 million years of separate evolution, the connectivity of the avian brain conforms to the same organisational principles as the mammalian brain

Strategic Knowledge Measurement and Management

Knowledge and intellectual capital are now recognized as vital resources for organizational survival and competitive advantage. A vast array of knowledge measures has evolved, spanning many disciplines. This chapter reviews knowledge measures focusing on groups of individuals (such as teams, business and organizations), as they reflect the stock or flow of knowledge, as well as enabling processes that enhance knowledge stocks and flows. The chapter emphasizes the importance of organizational value chains, pivotal talent pools and the link between knowledge and competitive success, in understanding the significance of today’s knowledge measures, and opportunities for future research and practice to enhance them

Bottom-up retinotopic organization supports top-down mental imagery

Finding a path between locations is a routine task in daily life. Mental navigation is often used to plan a route to a destination that is not visible from the current location. We first used functional magnetic resonance imaging (fMRI) and surface-based averaging methods to find high-level brain regions involved in imagined navigation between locations in a building very familiar to each participant. This revealed a mental navigation network that includes the precuneus, retrosplenial cortex (RSC), parahippocampal place area (PPA), occipital place area (OPA), supplementary motor area (SMA), premotor cortex, and areas along the medial and anterior intraparietal sulcus. We then visualized retinotopic maps in the entire cortex using wide-field, natural scene stimuli in a separate set of fMRI experiments. This revealed five distinct visual streams or ‘fingers’ that extend anteriorly into middle temporal, superior parietal, medial parietal, retrosplenial and ventral occipitotemporal cortex. By using spherical morphing to overlap these two data sets, we showed that the mental navigation network primarily occupies areas that also contain retinotopic maps. Specifically, scene-selective regions RSC, PPA and OPA have a common emphasis on the far periphery of the upper visual field. These results suggest that bottom-up retinotopic organization may help to efficiently encode scene and location information in an eye-centered reference frame for top-down, internally generated mental navigation. This study pushes the border of visual cortex further anterior than was initially expected

Strategic Marketing Management in the Nigerian Oil and Gas Industry:a Theoretical Framework

The purpose of this paper is to review the literature on strategic marketing management .. This study adopted a expost facto research methodology to examine the strategic marketing management literature in an attempt to attain their desired level of performance. The overall findings suggest that strategic marketing is a driver of organizational positioning in a dynamic environment, and that it helps to enhance the development of new product/service for existing markets. These findings, along with other interesting findings of the study, are discussed. From the empirical and anecdotal managerial evidence as well as from the literature implications are drawn for the efficient and effective strategic marketing practices in the Nigerian oil and gas industry. Based on the findings of the study, the concepts and principles of total quality management within a holistic framework it is recommended that (i) efforts should be made by organizational marketers towards understanding the relevant economic factors that affect both clients’ behaviour and the strategic options that may be adopted to cope with such behaviours; ((ii) in a constantly changing business environment, firms can adopt different strategic marketing practices since the yardstick is the enhancement of business performance

Usability and Psychosocial Impact of Decision Support to Increase Sexual Health Education in American Indian and Alaska Native Communities

Despite sexual and reproductive health disparities, few evidence-based sexual health education programs exist for American Indian/Alaska Native (AI/AN) youth, with even fewer tools available to assist AI/AN communities in adopting, implementing, and maintaining such programs. iCHAMPSS (Choosing And Maintaining effective Programs for Sex education in Schools) is a theory- and web-based decision-support-system designed to address dissemination barriers and increase the reach and fidelity of evidence-based programs (EBPs), specifically sexual health education programs. To investigate the potential of iCHAMPSS in AI/AN communities, we pilot-tested iCHAMPSS with adult stakeholders (N = 36) from agencies across the country that serve AI/AN communities. Stakeholders were recruited to review selected iCHAMPSS tools over two weeks in spring 2016. Pre- and post-surveys were administered to assess usability constructs, short-term psychosocial outcomes, and perceived feasibility. Data were analyzed using descriptive and non-parametric statistics. iCHAMPSS was perceived as acceptable, easy to use, credible, appealing, more helpful than current resources, and impactful of EBP adoption, implementation, and maintenance. Conversely, using iCHAMPSS significantly increased participants’ perceived barriers to adopting an EBP (p = 0.01). Overall, AI/AN stakeholders responded positively to iCHAMPSS, indicating the potential for adaptation to support the dissemination and implementation of evidence-based sexual health education in AI/AN communities

Modernization of Education Contents of Muhammadiyah, Nahdlatul Ulama, and Al Jam’iyatul Washliyah 1900-1942 in North Sumatera

This study aims to reveal how the process of modernization of education content on the organization Muhammadiyah, Nahdlatul Ulama and Al Jam'iyatul Washliyah years 1900-1942. The issues raised are: (1) how the historical background in modernizing education content of the three organizations; (2), how the modernization process of these organizations to arrange their education content; (3), how the these organizations dissemination of education content on the subjects. This is solved by historical method comprising the steps of: heuristics; second, verification; interpretation; historiography, and social history. The findings research informs: First, the three organizations have the same background in determining the education content, those are, first; the spirit leaders spreading Islam in accupation situation by orienting on Islamic education of the occupation, second; the intellectual contact internally an externally to conceive and build on the progress of Islamic education. Third; The strong desire to equate Islamic education progress with the western progress (colonization), fourth; The desire to realize the equality social among communities in receiving education and the world of work. The second finding is; the same formulate of education content material Islamic teaching that originated from AD and ART, but have different ways depending on modern education content. Muhammadiyah with revolutionary and Nahdlatul Ulama with evolutionary, and Al Jam'iyatul Washliyah with situasionery. the third finding is; the similarities of education content modernization process using a common and religious material. However they have differences on the distribution of the content in the subjects, Muhammadiyah is innovative and NahdlatulUlama is creative and Al Jam’iyatul Washliyah is very selective

KM Maturity Factors Affecting High Performance in Universities

This paper aims to measure Knowledge Management Maturity (KMM) in the universities to determine the impact of knowledge management on high performance. This study was applied on Al-Quds Open University in Gaza strip, Palestine. Asian productivity organization model was applied to measure KMM. Second dimension which assess high performance was developed by the authors. The controlled sample was (306). Several statistical tools were used for data analysis and hypotheses testing, including reliability Correlation using Cronbach’s alpha, “ANOVA”, Simple Linear Regression and Step Wise Regression.The overall findings of the current study suggest that KMM is suitable for measuring high performance. KMM assessment shows that maturity level is in level three. Findings also support the main hypothesis and it is sub- hypotheses. The most important factors effecting high performance are: Processes, KM leadership, People, KM Outcomes and Learning and Innovation. Furthermore the current study is unique by the virtue of its nature, scope and way of implied investigation, as it is the first comparative study in the universities of Palestine explores the status of KMM using the Asian productivity Model