1、喜树碱类衍生物抗HIV构效关系与作用机制研究2、HIV/AIDS患者疱疹病毒感染状况及性病患者的HIV感染状况分析

1、喜树碱类衍生物抗HIV构效关系与作用机制研究 喜树碱为传统的抗肿瘤药物。本研究对经过化学结构修饰的喜树碱类衍生物进行抗HIV活性及作用机制的研究，并初步探讨了其抗HIV构效关系。 我们对喜树碱类衍生物A系列化合物A1(喜树碱)、A2(10-羟基喜树碱)及A3(7-羟基喜树碱)进行了抗HIV活性检测。化合物A1和A3有较好的抗HIV-1和抗HIV-2活性，化合物A2没有显示抗HIV活性。表明化合物A1的C-10位上-OH基团修饰可能会降低抗HIV活性，化合物A1的C-7位上-CH2OH基团修饰和C-20位-CH3缺失可能会提高其抗HIV活性。对化合物A3和A1的抗HIV机制研究发现：二者对整合酶有一定的结合活性，对慢性感染H9/HIV-1ⅢB 和Jurkat/HIV-1ⅢB细胞中病毒复制没有抑制活性、不能阻断H9/HIV-1ⅢB与正常细胞间的融合，对重组的HIV-1蛋白酶和逆转录酶没有抑制活性。化合物A1和A3不具有选择性杀伤HIV-1ⅢB慢性感染的H9和Jurkat细胞系的作用。进一步进行化合物A3诱导 H9和H9/HIV-1ⅢB、Jurkat和Jurkat/HIV-1ⅢB的凋亡实验显示，化合物A3诱导感染HIV-1ⅢB和未感染病毒细胞的凋亡没有选择性。据此我们初步认为化合物A3和A1的抗HIV作用可能与抑制整合酶活性有关，该化合物可能还作用于其它靶点。 喜树碱类衍生物B系列中化合物B1为20(S)-O - [-O-( 1'-氧基-2',2',6',6'-四甲基哌啶-4'-丁二酸)]-20-喜树碱酯，化合物B2为20(S)-O - [-N-( 1'-氧基-2',2',6',6'-四甲基-1',2',5',6'-四氢吡啶酰胺)-4'-丙氨酸)]-20-喜树碱酯)。我们对化合物B1和B2进行了抗HIV活性检测。结果显示：化合物B2有较好的抗HIV-1和抗HIV-21、喜树碱类衍生物抗HIV构效关系与作用机制研究 喜树碱为传统的抗肿瘤药物。本研究对经过化学结构修饰的喜树碱类衍生物进行抗HIV活性及作用机制的研究，并初步探讨了其抗HIV构效关系。 我们对喜树碱类衍生物A系列化合物A1(喜树碱)、A2(10-羟基喜树碱)及A3(7-羟基喜树碱)进行了抗HIV活性检测。化合物A1和A3有较好的抗HIV-1和抗HIV-2活性，化合物A2没有显示抗HIV活性。表明化合物A1的C-10位上-OH基团修饰可能会降低抗HIV活性，化合物A1的C-7位上-CH2OH基团修饰和C-20位-CH3缺失可能会提高其抗HIV活性。对化合物A3和A1的抗HIV机制研究发现：二者对整合酶有一定的结合活性，对慢性感染H9/HIV-1ⅢB 和Jurkat/HIV-1ⅢB细胞中病毒复制没有抑制活性、不能阻断H9/HIV-1ⅢB与正常细胞间的融合，对重组的HIV-1蛋白酶和逆转录酶没有抑制活性。化合物A1和A3不具有选择性杀伤HIV-1ⅢB慢性感染的H9和Jurkat细胞系的作用。进一步进行化合物A3诱导 H9和H9/HIV-1ⅢB、Jurkat和Jurkat/HIV-1ⅢB的凋亡实验显示，化合物A3诱导感染HIV-1ⅢB和未感染病毒细胞的凋亡没有选择性。据此我们初步认为化合物A3和A1的抗HIV作用可能与抑制整合酶活性有关，该化合物可能还作用于其它靶点。 喜树碱类衍生物B系列中化合物B1为20(S)-O - [-O-( 1'-氧基-2',2',6',6'-四甲基哌啶-4'-丁二酸)]-20-喜树碱酯，化合物B2为20(S)-O - [-N-( 1'-氧基-2',2',6',6'-四甲基-1',2',5',6'-四氢吡啶酰胺)-4'-丙氨酸)]-20-喜树碱酯)。我们对化合物B1和B2进行了抗HIV活性检测。结果显示：化合物B2有较好的抗HIV-1和抗HIV-2活性，而化合物B1的抗HIV活性差。表明化合物B1的C-4’位-CH2被-NH取代，同时C-3’位-CH3修饰可能会提高其抗HIV活性。对化合物B2的抗HIV机制研究发现，化合物B2对慢性感染H9/HIV-1ⅢB细胞中病毒复制没有抑制活性、不能阻断H9/HIV-1ⅢB与正常细胞间的融合，对HIV-1蛋白酶、重组的HIV-1逆转录酶及整合酶没有抑制活性。化合物B2不具有选择性杀伤HIV-1ⅢB慢性感染的H9细胞系的作用。化合物B2抗HIV的作用机制还需进一步研究。 2、HIV/AIDS患者疱疹病毒感染状况及性病患者的HIV感染状况分析 疱疹病毒是AIDS患者合并感染的常见病原体。引起人类疾病的8种疱疹病毒与HIV感染及AIDS进展、机会性感染、恶性肿瘤密切相关。为了解HIV/AIDS患者人类8型疱疹病毒感染状况，我们检测了30例AIDS患者、40例HIV携带者及70例正常对照的液标本中8型疱疹病毒感染状况。采用ELISA法检测单纯疱疹病毒1型(HSV-1)、单纯疱疹病毒2型(HSV-2)、水痘-带状疱疹病毒(VZV)和巨细胞病毒(CMV)；采用PCR法检测EB病毒(EBV)、疱疹病毒6型(HHV-6)、疱疹病毒7型(HHV-7)及疱疹病毒8型(HHV-8)。结果显示，HIV/AIDS患者中HSV-1、HSV-2、VZV、CMV、HHV-6、HHV-8 阳性率均高于健康体检者，其中AIDS患者VZV感染率与HIV携带者有显著性差异；在AIDS患者中多种疱疹病毒共感染普遍存在，必须重视HIV/AIDS患者合并疱疹病毒感染的防治。 性病可促进HIV的传播，了解性病患者的HIV感染状况及临床特征具有重要的意义。在自愿接受HIV咨询检测的基础上，对临床确诊的412例性病患者进行HIV-1/2抗体检测，并对其临床特征进行分析研究。结果显示412例性病患者的HIV检出率为2.9%。性病患者中检出HIV阳性率依次为：尖锐湿疣(6.2%)、生殖器疱疹(4.2%)、梅毒(3.4%)、淋病(1.5%)及非淋菌性尿道炎(1.0%)。83.3%合并感染HIV的性病患者存在多性伴，商业性行为普遍存在，安全套使用率极低现象。感染HIV的尖锐湿疣及生殖器疱疹患者以频繁复发为突出表现，1例合并感染HIV的梅毒患者半年即进展为神经梅毒。性病患者是HIV感染的重要高危人群，危险性行为是其感染HIV和其它性病的主要原因，应该加强性病患者的HIV检测。对临床上频繁复发的尖锐湿疣及生殖器疱疹患者、快速进展的梅毒患者应高度怀疑合并HIV感染的可能。

Planning and Teaching Compliant Motion Strategies

This thesis presents a new high level robot programming system. The programming system can be used to construct strategies consisting of compliant motions, in which a moving robot slides along obstacles in its environment. The programming system is referred to as high level because the user is spared of many robot-level details, such as the specification of conditional tests, motion termination conditions, and compliance parameters. Instead, the user specifies task-level information, including a geometric model of the robot and its environment. The user may also have to specify some suggested motions. There are two main system components. The first component is an interactive teaching system which accepts motion commands from a user and attempts to build a compliant motion strategy using the specified motions as building blocks. The second component is an autonomous compliant motion planner, which is intended to spare the user from dealing with "simple" problems. The planner simplifies the representation of the environment by decomposing the configuration space of the robot into a finite state space, whose states are vertices, edges, faces, and combinations thereof. States are inked to each other by arcs, which represent reliable compliant motions. Using best first search, states are expanded until a strategy is found from the start state to a global state. This component represents one of the first implemented compliant motion planners. The programming system has been implemented on a Symbolics 3600 computer, and tested on several examples. One of the resulting compliant motion strategies was successfully executed on an IBM 7565 robot manipulator.

The use of podcasts to enhance research-teaching linkages in undergraduate nursing students.

An understanding of research is important to enable nurses to provide evidencebasedcare. However, undergraduate nursing students often find research a challenging subject. The purpose of this paper is to present an evaluation of the introduction of podcasts in an undergraduate research module to enhance research teaching linkages between the theoretical content and research in practice and improve the level of student support offered in a blended learning environment. Two cohorts of students (n=228 and n=233) were given access to a series of 5 “guest speaker” podcasts made up of presentations and interviews with research experts within Edinburgh Napier. These staff would not normally have contact with students on this module, but through the podcasts were able to share their research expertise and methods with our learners. The main positive results of the podcasts suggest the increased understanding achieved by students due to the multi-modal delivery approach, a more personal student/tutor relationship leading to greater engagement, and the effective use of materials for revision and consolidation purposes. Negative effects of the podcasts centred around problems with the technology, most often difficulty in downloading and accessing the material. This paper contributes to the emerging knowledge base of podcasting in nurse education by demonstrating how podcasts can be used to enhance research-teaching linkages and raises the question of why students do not exploit the opportunities for mobile learning.

Reflections on the development of a dynamic learning, teaching and assessment strategy.

Developing learning, teaching and assessment strategies that foster ongoing engagement and provide inspiration to academic staff is a particular challenge. This paper demonstrates how an institutional learning, teaching and assessment strategy was developed and a ‘dynamic’ strategy created in order to achieve the ongoing enhancement of the quality of the student learning experience. The authors use the discussion of the evolution, development and launch of the Strategy and underpinning Resource Bank to reflect on the hopes and intentions behind the approach; firstly the paper will discuss the collaborative and iterative approach taken to the development of an institutional learning, teaching and assessment strategy; and secondly, the development of open access educational resources to underpin the strategy. The paper then outlines staff engagement with the resource bank and positive outcomes which have been identified to date, identifies the next steps in achieving the ambition behind the strategy and outlines the action research and fuller evaluation which will be used to monitor progress and ensure responsive learning at institutional level.

‘Novice Teachers’ Views of an Introductory Workshop about Teaching in the Biosciences.

Seven regional networking events, aimed at supporting and developing ‘early stage’ novice university bioscience teachers were held across the UK. These workshops allowed 230 participants to reflect on teaching styles, learn about Higher Education Academy resources and discuss strategies to deal with a range of teaching situations. Post-event feedback was sought, and the results are presented in this paper. Feedback on the events was overwhelmingly positive, highlighting the need for such events to support the development of new teachers in higher education. Institutional training varies and these opportunities for sharing experiences, asking questions, networking and reflection on teaching practice were highly regarded. Most participants felt more confident about their teaching and believed that students were more directly engaged in their teaching after attending the events. Recommendations for support of this category of teacher include provision of discipline-specific events, opportunity for local area networking and support for the development of reflective practice in teaching and learning.

Robotic Assembly of Naturally Varying Food Items via Teaching by Example

T. G. Williams, J.J. Rowland, and Lee M.H., Robotic Assembly of Naturally Varying Food Items via Teaching by Example, 9th Int. Symp. on Intelligent Robotic Systems (SIRS 2001), July 2001, France, pp133-142.

Teaching from Examples in Assembly and Manipulation of Snack Food Ingredients by Robot

T. G. Williams, J.J. Rowland, and Lee M.H., Teaching from Examples in Assembly and Manipulation of Snack Food Ingredients by Robot, Proc. IEEE/RSJ Int. Conf. on Robots and Systems (IROS 2001), Nov., 2001, pp2300-2305.

Teaching by Example in Food Assembly by Robot

T. G. Williams, J.J. Rowland, Lee M.H. and M.J. Neal Teaching by Example in Food Assembly by Robot, Proc. 2000 IEEE Int. Conf. On Robotics and Automation, San Francisco, April 2000, pp3247-52.

Thinking with and outside the box: developing computer support for evidence teaching

B. Schafer, J. Keppens and Q. Shen. Thinking with and outside the Box: Developing Computer Support for Evidence Teaching. P. Robert and M. Redmayne (Eds.), Innovations in Evidence and Proof: Integrating Theory, Research and Teaching, pp. 139-158, 2007.

HIV/AIDS and national security

McInnes, C., 'HIV/AIDS and national security', in: AIDS and Governance, N. Poku, A. Whiteside and B. Sandkjaer (eds.),(Aldershot: Ashgate, 2007), pp.93-111 RAE2008

BitBox!: A case study interface for teaching real-time adaptive music composition for video games

Real-time adaptive music is now well-established as a popular medium, largely through its use in video game soundtracks. Commercial packages, such as fmod, make freely available the underlying technical methods for use in educational contexts, making adaptive music technologies accessible to students. Writing adaptive music, however, presents a significant learning challenge, not least because it requires a different mode of thought, and tutor and learner may have few mutual points of connection in discovering and understanding the musical drivers, relationships and structures in these works. This article discusses the creation of ‘BitBox!’, a gestural music interface designed to deconstruct and explain the component elements of adaptive composition through interactive play. The interface was displayed at the Dare Protoplay games exposition in Dundee in August 2014. The initial proof-of- concept study proved successful, suggesting possible refinements in design and a broader range of applications.

Teaching English tense and aspect with the help of cognitive grammar: An empirical study

Form-focused instruction is usually based on traditional practical/pedagogical grammar descriptions of grammatical features. The comparison of such traditional accounts with cognitive grammar (CG) descriptions seems to favor CG as a basis of pedagogical rules. This is due to the insistence of CG on the meaningfulness of grammar and its detailed analyses of the meanings of particular grammatical features. The differences between traditional and CG rules/descriptions are exemplified by juxtaposing the two kinds of principles concerning the use of the present simple and present progressive to refer to situations happening or existing at speech time. The descriptions provided the bases for the instructional treatment in a quasi-experimental study exploring the effectiveness of using CG descriptions of the two tenses, and of their interplay with stative (imperfective) and dynamic (perfective) verbs, and comparing this effectiveness with the value of grammar teaching relying on traditional accounts found in standard pedagogical grammars. The study involved 50 participants divided into three groups, with one of them constituting the control group and the other two being experimental ones. One of the latter received treatment based on CG descriptions and the other on traditional accounts. CG-based instruction was found to be at least moderately effective in terms of fostering mostly explicit grammatical knowledge and its effectiveness turned out be comparable to that of teaching based on traditional descriptions.

Teaching Competences and their Development Via Video-Recording

The article deals with use of case studies for professional preparation of teachers to be. One of the suitable ways to develop professional teaching competences is to apply the method of a case study. A case study means a complex and creative solution for a given teaching situation in simulated teaching conditions. It is based on interactive and situational education and decision taking. A case study improves not only professional and teaching competences for becoming teachers – it also fulfi ls the task to develop at students their auto-evaluating and auto-refl exing skills. To increase professional competences it is mandatory to do a complex analysis of the video-record for the implemented study. A complex analysis is a subject of the research project of a student grant agency at the University of West Bohemia in Pilsen.