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The development of bioinformatic and chemoinformatic approaches for structure-activity modelling and discovery of antimicrobial peptidesFjell, Christopher David 05 1900 (has links)
The emergence of pathogens resistant to available drug therapies is a pressing global
health problem. Antimicrobial peptides (AMPs) may potentially form new therapeutics to
counter these pathogens. AMPs are key components in the mammalian innate immune system
and are responsible for both direct killing and immunomodulatory effects in host defense
against pathogenic organisms. This thesis describes computational methods for the
identification of novel natural and synthetic AMPs.
A bioinformatic resource was constructed for classification and discovery of gene-
coded AMPs, consisting of a database of clustered known AMPs and a set of hidden Markov
models (HMMs). One set of 146 clusters was based on the mature peptide sequence, and one
set of 40 clusters was based on propeptide sequence. The bovine genome was analyzed using
the AMPer resources, and 27 of the 34 known bovine AMPs were identified with high
confidence and up to 69 AMPs were predicted to be novel peptides. One novel cathelicidin
AMP was experimentally verified as up-regulated in response to infection in bovine intestinal
tissue.
A chemoinformatic analysis was performed to model the antibacterial activity of short
synthetic peptides. Using high-throughput screening data for the activities of over 1400
peptides of diverse sequence, quantitative structure-activity relation (QSAR) models were
created using artificial neural networks and physical characteristics of the peptide that included
three-dimensional atomic structure. The models were used to predict the activity of a set of
approximately 100,000 peptide sequence variants. After ranking the predicted activity, the
models were shown to be very accurate. When 200 peptides were synthesized and screened
using four levels of expected activity, 94% of the top 50 peptides expected to have the highest
level of activity were found to be highly active. Several promising candidates were synthesized
with high quality and tested against several multi- antibiotic-resistant pathogens including
clinical strains of Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecalis and
Escherichia coli. These peptides were found to be highly active against these pathogens as
determined by minimal inhibitory concentration; this serves as independent confirmation of the
effectiveness of high-throughput screening and in silico analysis for identifying peptide
antibiotic drug leads.
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Host and pathogen sensory systems as targets for therapeutic interventionKindrachuk, K. Jason 31 July 2007 (has links)
A new paradigm for the treatment of infectious disease is through the modulation of innate immune responses. In this capacity, host defense peptides (HDPs) and synthetic Toll-like receptor 9 (TLR9) ligands have the greatest demonstrated potentials. The work presented here considers mechanisms for the improvement of these treatments through optimization, or in the case of HDPs the minimization, of the interactions of these ligands with sensory receptors.<p>Toll-like Receptor 9 activates the innate immune system in response to microbial DNA or immune-modulating oligodeoxynucleotides. While cell stimulation experiments demonstrate the preferential activating ability of CpG-containing nucleic acids, direct binding investigations have reached contradictory conclusions regarding the sequence-specificity of TLR9 ligand binding. To address this discrepancy the characterization of human TLR9 ligand binding properties is reported. TLR9 has a high degree of ligand specificity in being able to discriminate not only CpG dinucleotides, but also higher order six nucleotide motifs that mediate species-specific activation. However, TLR9 ligand binding is also functionally influenced by nucleic acids in a sequence-independent manner both in vitro and in cell proliferation experiments. A model is proposed in which TLR9 activation is mediated specifically by CpG-containing ligands while sensitivity of the receptor is modulated by the absolute concentration of nucleic acids in a sequence-independent fashion. <p>Host defense peptides are among the leading candidates to combat antibiotic resistant bacterial strains. Recently, HDPs have been demonstrated to function as ligands for the bacterial sensory kinase PhoQ resulting in the induction of virulence and adaptive responses. Thus, concerns have been raised regarding therapeutic applications of HDPs. Here a methodology is described that permits discrimination and quantification of the distinct, but related, peptide behaviors of direct antimicrobial activity and PhoQ ligand potential. Utilizing peptide derivatives of the model HDP Bac2A it is demonstrated that antimicrobial efficiency is significantly, and inversely, related to PhoQ ligand efficacy. This provides a rational basis for HDP selection with greater therapeutic potential and minimized potential for initiation of bacterial resistance.
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Why do Things Fall Apart? : A Psychological Analysis of Okonkwo's Personality and his Ultimate Demise in Chinua Achebe's Novel Things Fall ApartCowlin, Justin Lee January 2011 (has links)
There are very few works not associated with the Western canon to have received as much attention as Chinua Achebe’s novel Things Fall Apart (Ogbaa 1). However, contrary to the many post-colonial interpretations of this novel, this essay employs a psychoanalytical literary approach to discuss the cause of the protagonist’s eventual demise, based on the premise that human behaviour is driven by an unconscious process. Consequently, this essay argues that following the ego’s inability to repress the infantile demands of the unconscious, the preconscious and the conscious self, ever more compulsive, repetitive and neurotic behaviours are displayed. Furthermore, this essay argues that Okonkwo’s relationship to his mother plays a significant role in explaining the tense relationship with his own father and sons. Subsequently, the protagonist’s self-confidence turns to pride and his masculinity develops into totalitarian rule leading to uncontrollable rage, Okonkwo’s world literally falls apart.
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Modeling and Defending Against Internet Worm AttacksChen, Zesheng 09 April 2007 (has links)
As computer and communication networks become prevalent, the Internet has been a battlefield for attackers and defenders. One of the most powerful weapons for attackers is the Internet worm. Specifically, a worm attacks vulnerable computer systems and employs self-propagating methods to flood the Internet rapidly. The objective of this research is to characterize worm attack behaviors, analyze Internet vulnerabilities, and develop effective countermeasures. More specifically, some fundamental factors that enable a worm to be designed with advanced scanning methods are presented and investigated through mathematical modeling, simulations, and real measurements.
First, one factor is an uneven vulnerable-host distribution that leads to an optimal scanning method called importance scanning. Such a new method is developed from and named after importance sampling in statistics and enables a worm to spread much faster than both random and routable scanning. The information of vulnerable-host distributions, however, may not be known before a worm is released. To overcome this, worms using two sub-optimal methods are then investigated. One is a self-learning worm that can accurately estimate the underlying vulnerable-host distribution while propagating. The other is a localized-scanning worm that has been exploited by Code Red II and Nimda worms. The optimal localized scanning and three variants of localized scanning are also studied. To fight against importance-scanning, self-learning, and localized-scanning worms, defenders should scatter applications uniformly in the entire IP-address space from the viewpoint of game theory. Next, a new metric, referred to as the non-uniformity factor, is presented to quantify both the unevenness of a vulnerable-host distribution and the spreading ability of network-aware worms. This metric is essentially the Renyi information entropy and better characterizes the non-uniformity of a distribution than the Shannon entropy. Finally, another fundamental factor is topology information that enables topological-scanning worms. The spreading dynamics of topological-scanning worms are modeled through a spatial-temporal random process and simulated with both real and synthesized topologies.
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Exploring the Policy Marketing Event of All-out Defense Education¡ÐA Case of Amphibious Warriors Battle CampLin, Ming-da 22 July 2011 (has links)
Since the formal implementation of the All-out Defense Education Law, the Ministry of National Defense has actively organized relevant departments and bureaus to promote the ideas of All-out Defense Education policy through a diverse array of publicities and activities. Among these activities, the All-out Defense Military Summer Camp, organized every July and August by integrating the characteristics of all army services, is the most popular activity, and has received wide feedback from the youths.
¡§Actualization of All-out Defense Education policies and in-depth and grass-root work for Total National Defense¡¨ is the theme for the All-out Defense Military Summer Camp organized by the Ministry of National Defense. This study applied the perspective of marketing strategies, and investigated the students attending the ¡§2010 Amphibious Warriors Battle Camp¡¨ using questionnaires. It evaluated student backgrounds and motivation for participation, as well as the relationship with customer equity. Collected data is done through Descriptive Statistics Analysis, such as Independent t-test, One-way ANOVA, Pearson Product-moment Correlation. Conclusion is listed as below: ¡§The summer camp reaches the purpose of All-Out Defense Policy; participants¡¦ motivation is highly influenced by¡¥to become mature¡¦, customer equity is highly influenced by value equity; participants¡¦ motivation and customer equity are highly influenced by some different kinds of background; motivation and customer equity has a positive relationship; three dimensions of customer equity have a positive relationship¡Flots of students have great will to receive the information of army.¡¨
Based on the conclusions, some suggestions proposed as follows:
1. To consider the needs of different targets in detail demands using more accurate market segmentation, and by providing more diverse activities and courses; the activity can be combined with the promotion of the army recruitment policy to improve the many functions and value of combat camps.
2. In order to fully promote the brand of All-out Defense Education policies, ¡§same branding but different marketing targets¡¨ as well as ¡§same brands, different logos and slogans¡¨ can be used in combination with other marketing tactics to improve the understanding and support of citizens to All-out Defense Education policies.
3. To take advantage of social networking websites that many youths and students use to construct an electronic forum or communications platform allowing students from the annual Combat Camps to share their experiences and opinions. At the same time, special activities can be planned for students with exceptional participation to maintaining a strong bond with the customers of All-out Defense Education.
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The Study on the Effectiveness of All-out Defense in the High School EducationYu, Yuang-chao 30 July 2011 (has links)
We have been operated the All-out Defense education for five years. The purpose of this study is to investigate the working effectiveness of All-out Defense education. The content of the test was based on ¡§the factors of influencing learning effectiveness¡¨. For supporting the above-mentioned purposes, I used questionnaire investigation method to collect the material data. A total of 570 questionnaires were sent out to a senior high school in Kaohsiung City , and the effective samples are 498. Describing statistics, discriminate analysis, t test, and Pearsonion correlation coefficient, were performedby SPSS statistics software to analyze and explain the raw data. Besides, I have interviewed a teacher who has winned the award of Teaching Excellence recognition in 2010. He made a description of operating the national defense education for the school. The results of this study were analyzed and discussed as follows. First, after operating the national defence education for five years, the preliminary effect has been noticed in the senior high school. Second, there was a significant difference between students¡¦ background and influencing factors of learning. Third, there was no significant difference between students¡¦ background and learning results. Forth, influencing factors have big impact toward learning effectiveness.
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An Exploration of Healthcare Information System Development Project Based on the Views of Organizational Defense --- A Case Study of E HospitalHung, Chih-lung 02 September 2005 (has links)
Introducing an information system is an organizational learning process, during the process of development an information system , organizational members learn how to introduce information technology into an enterprise. While learning, however, most of individuals always act defensively without any awareness, when solving their problems. For the purpose of Organizational learning, these defensive behaviors will bring counterproductive or unintended consequences or limited learning, and result in the information system which cannot completely meet the business needs or cause project¡¦s schedule delay.
In this research, we use the process research model methodology which developed by D. Robey and M. Newman in 1992 year and 1996 year, identify the 16 sequences event process in the case of healthcare information project of E hospital, and define them as either encounters or episodes. From the view of organizational defense, we analyze these events base on the theories of defense mechanism from Argyris and documents about organizational defense from information management. The analyzing results show that there indeed exist many defensive behaviors during the development of project of E hospital, and thus cause negative effect. This research offers these defensive phenomenon for the CIO and project managers to take precaution against same mistake while implementing information project, and help organizational members learning effectively while introducing an information system, in order to reduce risk of project failure and improve control of information project¡¦s cost, quality and schedule.
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Russia And The Western Missile Defense Initiatives: Towards A Partnership In The Making?Civelik, Ismail 01 February 2012 (has links) (PDF)
This thesis analyzes the Western missile defense initiatives and their role in Russia' / s relations with NATO and the U.S. The main question of this thesis is whether the Western missile defense initiatives have paved the way for a new era of cooperation between Russia and the West or not. The main argument of this thesis is that Russia has failed to collaborate with NATO in a meaningful manner on missile defense issue as Russia has not adjusted its security policies and nuclear strategy, which are still based on the Cold War thinking, to the changing conditions of global security in the post Cold War era. The missile defense initiatives have a negative impact on the relations between Russia and the West due to the intransigent stance of Russia on this issue. A robust cooperation can only be achieved between Russia and NATO if Moscow changes its Cold War mentality about global security issues.
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The Prototype of Defense Strategy in IndiaHsu, Yi-Jia 29 December 2007 (has links)
From Britain¡¦s point of view, the problems of security and defense in India subcontinent were far greater than those of the maintenance of law and order and imperial rule in the subcontinent itself. For Indian subcontinent, it was the pivot of British power in all of Asia. Furthermore, British possessed the maritime supremacy, the main threat came from the land, especially form the Northwest frontier.
British strategy for the defense of India¡¦s land frontiers was based on the following three points: (1) to maintain firm military strength in the most vulnerable parts of the frontier, i.e., the Northwest frontier and Baluchistan, and to keep the tribes of this area pacified or under their control by ¡§divide and rule¡¨ tactics, for the purpose of consolidating integrity of the Northwest frontier and the security of India subcontinent; (2) to encourage the establishment of a string of buffer states all along the perimeter of the subcontinent and to maintain influence or friendly relations with them; and (3) to prevent any contiguous territory and states form coming under the control of a strong power, notably Russia, if necessary by forceful means.
Although there are many historical and geographic constraints in South Asia defense considerations, the present defense strategy of India has to be designed to meet the new circumstances. Throughout the years of independence the main security concern of India has been defense over both land and sea problems. On land, India has to handle the relationship with Pakistan and protect the Northeast frontier against the threat from China. In the past, the Northwest frontier was an unified area, after the retreat of British power in 1947, the geographical and strategic unity of the India subcontinent was broken. Moreover, India has nearly a coastline of 7,000 km long, but India doesn¡¦t have the maritime supremacy, so that it should be compelled to deal with potential threat from India ocean.
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Research for the military mission of disaster-relief, take mental health work for exampleYan, Jiou-en 31 July 2008 (has links)
Research for the military mission of disaster-relief, take mental
Health work for example
Abstract
National defense means defense of the national security. No matter in peacetime or wartime, the military mission of protecting the country is to ensure the welfare of the people and the national security under the consensus of civil defense. The motive of this research originates from the experience of the researchers who were actually involved in the disaster mental health work. Based on the aspect, the research deliberates on the problems which the military faces during the time of disaster-relief, and facilitates the positive effect and response of ¡§the civil mobilization¡¨.
The purpose of the research is to adapt the military mission and the disaster mental health work, so that those will accord with the transformation of national defense policy and military thought. The text mainly discusses the differences between the real experience and the policy of mental health, and focuses on the valuable experience of the key persons, which collects the opinions from the papers and investigation. In the view of overall considerations and public policy, it researches about the development and meaningful framework of the disaster mental health work and the way which makes the military receiving much better care and multicultural counseling. The results also provide a reference about the research of the military mental health work.
¡§The national defense is not only the combat, but also the honorable career.¡¨ Nowadays, the military execute the mission of domestic disaster-relief lawfully. It is not only a kind of social responsibility, but also suits the wishes of the society. The long-term development of disaster mental health work can exhibit the professional value of the modern military. ¡¨To accept and win the traditional or modern war at the same time¡¨ is worth the common hopes of the civil. We hope much more that, when the disasters occur and threaten the beautiful island, Taiwan, the military can tell the civil at the first time:¡¨ Be relieved, The military are already ready for anything¡¨.
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