A FUNCTIONAL, COMPARATIVE AND CLINICAL ANALYSIS OF SPERM-BORNE OOCYTE ACTIVATING FACTOR, PAWP

Successful fertilization depends upon the activation of metaphase II arrested oocytes by sperm-borne oocyte activating factor (SOAF). Failure of oocyte activation is considered as the cause of treatment failure in a proportion of infertile couples. SOAF induces the release of intracellular calcium in oocyte which leads to meiotic resumption and pronuclear formation. Calcium release is either in the form of single calcium transient in echinoderm and amphibian oocytes or several calcium oscillations in ascidian and mammalian oocytes. Although the SOAF attributes are established, it is not clear which sperm protein(s) play such role. Sperm postacrosomal WW binding protein (PAWP) satisfies a developmental criteria set for a candidate SOAF. This study shows that recombinant human PAWP protein or its transcript acts upstream of calcium release and fully activates the amphibian and mammalian oocytes. Interference trials provided evidence for the first time that PAWP mediates sperm-induced intracellular calcium release through a PPXY/WWI domain module in Xenopus, mouse and human oocytes. Clinical applications of PAWP were further investigated by prospective study on the sperm samples from patients undergoing intracytoplasmic sperm injection (ICSI). PAWP expression level, analyzed by flow cytometry, was correlated to ICSI success rate and embryonic development. This study also explored the developmental expression of the other SOAF candidate, PLCζ in male reproductive system and its function during fertilization. Our findings showed for the first time that PLCζ most likely binds to the sperm head surface during epididymal passage and is expressed in epididymis. We demonstrated that PLCζ is also compartmentalized early in spermiogenesis and thus could play an important role during spermiogenesis. Detailed analysis of in vitro fertilization revealed that PLCζ disappears from sperm head during acrosome reaction and is not detectable during sperm incorporation into the oocyte cytoplasm. In conclusion, this dissertation provides evidence for the essential non-redundant role of sperm PAWP in amphibian and mammalian fertilization; recommends PAWP as a biomarker for prediction of ICSI outcomes in infertile couples; and proposes that sperm PLCζ may have functions other than inducing oocyte activation during fertilization.

Application-Specific Instruction Set Processor for SoC implementation of Modern Signal Processing Algorithms

A novel application-specific instruction set processor (ASIP) for use in the construction of modern signal processing systems is presented. This is a flexible device that can be used in the construction of array processor systems for the real-time implementation of functions such as singular-value decomposition (SVD) and QR decomposition (QRD), as well as other important matrix computations. It uses a coordinate rotation digital computer (CORDIC) module to perform arithmetic operations and several approaches are adopted to achieve high performance including pipelining of the micro-rotations, the use of parallel instructions and a dual-bus architecture. In addition, a novel method for scale factor correction is presented which only needs to be applied once at the end of the computation. This also reduces computation time and enhances performance. Methods are described which allow this processor to be used in reduced dimension (i.e., folded) array processor structures that allow tradeoffs between hardware and performance. The net result is a flexible matrix computational processing element (PE) whose functionality can be changed under program control for use in a wider range of scenarios than previous work. Details are presented of the results of a design study, which considers the application of this decomposition PE architecture in a combined SVD/QRD system and demonstrates that a combination of high performance and efficient silicon implementation are achievable. © 2005 IEEE.

CORDIC based application-specific instruction set processor for QRD/SVD

An application specific programmable processor (ASIP) suitable for the real-time implementation of matrix computations such as Singular Value and QR Decomposition is presented. The processor incorporates facilities for the issue of parallel instructions and a dual-bus architecture that are designed to achieve high performance. Internally, it uses a CORDIC module to perform arithmetic operations, with pipelining of the internal recursive loop exploited to multiplex the two independent micro-rotations onto a single piece of hardware. The net result is a flexible processing element whose functionality can be changed under program control, which combines high performance with efficient silicon implementation. This is illustrated through the results of a detailed silicon design study and the applications of the techniques to a combined SVD/QRD system.

Evaluation of predicted network modules in yeast metabolism using NMR-based metabolite profiling

Genome-scale metabolic models promise important insights into cell function. However, the definition of pathways and functional network modules within these models, and in the biochemical literature in general, is often based on intuitive reasoning. Although mathematical methods have been proposed to identify modules, which are defined as groups of reactions with correlated fluxes, there is a need for experimental verification. We show here that multivariate statistical analysis of the NMR-derived intra- and extracellular metabolite profiles of single-gene deletion mutants in specific metabolic pathways in the yeast Saccharomyces cerevisiae identified outliers whose profiles were markedly different from those of the other mutants in their respective pathways. Application of flux coupling analysis to a metabolic model of this yeast showed that the deleted gene in an outlying mutant encoded an enzyme that was not part of the same functional network module as the other enzymes in the pathway. We suggest that metabolomic methods such as this, which do not require any knowledge of how a gene deletion might perturb the metabolic network, provide an empirical method for validating and ultimately refining the predicted network structure.

Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains.

Macro domains constitute a protein module family found associated with specific histones and proteins involved in chromatin metabolism. In addition, a small number of animal RNA viruses, such as corona- and toroviruses, alphaviruses, and hepatitis E virus, encode macro domains for which, however, structural and functional information is extremely limited. Here, we characterized the macro domains from hepatitis E virus, Semliki Forest virus, and severe acute respiratory syndrome coronavirus (SARS-CoV). The crystal structure of the SARS-CoV macro domain was determined at 1.8-Å resolution in complex with ADP-ribose. Information derived from structural, mutational, and sequence analyses suggests a close phylogenetic and, most probably, functional relationship between viral and cellular macro domain homologs. The data revealed that viral macro domains have relatively poor ADP-ribose 1"-phosphohydrolase activities (which were previously proposed to be their biologically relevant function) but bind efficiently free and poly(ADP-ribose) polymerase 1-bound poly(ADP-ribose) in vitro. Collectively, these results suggest to further evaluate the role of viral macro domains in host response to viral infection.

Application of a Generic Curriculum Change Management Process to Motivate and Excite Students

The School of Mechanical and Aerospace Engineering at Queen’s University Belfast is committed to enhancing the quality of student learning. A plan to implement curriculum change around this goal has been formulated and is already several years underway. A specific part of the plan involved instigating a first year introductory module to engage the students in the practice of their engineering discipline. The complicated nature of devising this type of module with regard to objectives, resources, timeframe and the number of students involved meant that a very systematic approach had to be adopted. This paper presents the simple but definitive change management process that facilitated in the creation of a first year Introduction to Engineering module. The generic nature of this process is described and its application to other facets of curriculum change is discussed. Within this process the importance of collaboration to establish a forward momentum is emphasised. This enables academic staff to progress as a group and build curriculum development based on their own experiences, expertise and established practice

Loss of the LAT adaptor converts antigen-responsive T cells into pathogenic effectors that function independently of the T cell receptor.

Despite compromised T cell antigen receptor (TCR) signaling, mice in which tyrosine 136 of the adaptor linker for activation of T cells (LAT) was constitutively mutated (Lat(Y136F) mice) accumulate CD4(+) T cells that trigger autoimmunity and inflammation. Here we show that equipping postthymic CD4(+) T cells with LATY136F molecules or rendering them deficient in LAT molecules triggers a lymphoproliferative disorder dependent on prior TCR engagement. Therefore, such disorders required neither faulty thymic T cell maturation nor LATY136F molecules. Unexpectedly, in CD4(+) T cells recently deprived of LAT, the proximal triggering module of the TCR induced a spectrum of protein tyrosine phosphorylation that largely overlapped the one observed in the presence of LAT. The fact that such LAT-independent signals result in lymphoproliferative disorders with excessive cytokine production demonstrates that LAT constitutes a key negative regulator of the triggering module and of the LAT-independent branches of the TCR signaling cassette.

Wholeness of healing: an innovative Student-Selected Component introducing United Kingdom medical students to the spiritual dimension in healthcare.

Objective: This Student Selected Component (SSC) was designed to equip United Kingdom (UK) medical students to engage in whole-person care. The aim was to explore students' reactions to experiences provided, and consider potential benefits for future clinical practice.

Methods: The SSC was delivered in the workplace. Active learning was encouraged through facilitated discussion with and observation of clinicians, the palliative team, counselling services, hospital chaplaincy and healing ministries; sharing of medical histories by patients; and training in therapeutic communication. Assessment involved reflective journals, literature appraisal, and role-play simulation of the doctor-patient consultation. Module impact was evaluated by analysis of student coursework and a questionnaire.

Results: Students agreed that the content was stimulating, relevant, and enjoyable and that learning outcomes were achieved. They reported greater awareness of the benefit of clinicians engaging in care of the "whole person" rather than "the disease." Contributions of other professions to the healing process were acknowledged, and students felt better equipped for discussion of spiritual issues with patients. Many identified examples of activities which could be incorporated into core teaching to benefit all medical students.

Conclusion: The SSC provided relevant active learning opportunities for medical students to receive training in a whole-person approach to patient care.

Teaching and Learning Guide for 'Modern Problems of Editing...'

Companion piece to my earlier article in Literature Conmpass: 'Modern Problems of Editing: The Two Texts of Doctor Faustus'. Provides a model for a module based on the topic of that article.

Many-body theory calculations of positron binding to negative ions

A many-body theory approach developed by the authors [Phys. Rev. A 70, 032720 (2004)] is applied to positron bound states and annihilation rates in atomic systems. Within the formalism, full account of virtual positronium (Ps) formation is made by summing the electron-positron ladder diagram series, thus enabling the theory to include all important many-body correlation effects in the positron problem. Numerical calculations have been performed for positron bound states with the hydrogen and halogen negative ions, also known as Ps hydride and Ps halides. The Ps binding energies of 1.118, 2.718, 2.245, 1.873 and 1.393 eV and annihilation rates of 2.544, 2.482, 1.984, 1.913 and 1.809 ns^{-1}, have been obtained for PsH, PsF, PsCl, PsBr and PsI, respectively.

A 60 GHz wide tuning range SiGe bipolar VCO for HDMI and wireless docking applications

A wide tuning range voltage controlled oscillator (VCO) with novel architecture is proposed in this work. The entire circuit consists of a VCO core, a summing circuit, a single-ended to differential (STD) converter and a buffer amplifier. The VCO core oscillates at half the desired frequency and the second harmonic of the VCO core is extracted by the summing circuit, which is then converted to a differential pair by the STD. The entire VCO circuit operates from 58.85 to 70.85 GHz with 20% frequency tuning range. The measured VCO gain is less than 1.6 GHz/V. The measured phase noise at 3 MHz offset is less than -78 dBc/Hz across the entire tuning range. The differential phase error of the output signals is measured by down converting the VCO output signals to low gigahertz frequency using an on-chip mixer. The measured differential phase error is less than 8°. The VCO circuit, which is constructed using 0.35 µm SiGe technology, occupies 770 × 550 µm2 die area and consumes 62 mA under 3.5 V supply.

Autoclave Cure Simulation of Composite Structures Applying Implicit and Explicit FE

Simulation of the autoclave manufacturing technique of composites can yield a preliminary estimation of induced residual thermal stresses and deformations that affect component fatigue life, and required tolerances for assembly. In this paper, an approach is proposed to simulate the autoclave manufacturing technique for unidirectional composites. The proposed approach consists of three modules. The first module is a Thermo-chemical model to estimate the temperature and the degree of cure distributions in the composite part during the cure cycle. The second and third modules are a sequential stress analysis using FE-Implicit and FE-Explicit respectively. User-material subroutine is used to model the Viscoelastic properties of the material based on theory of micromechanics.

Virtual Manufacturing of Composite Structures Applying Implicit and Explicit FE Techniques

Virtual manufacturing of composites can yield an initial early estimation of the induced residual thermal stresses that affect component fatigue life, and deformations that affect required tolerances for assembly. Based on these estimation, the designer can make early decisions, which can help in reducing cost, regarding changes in part design or material properties. In this paper, an approach is proposed to simulate the autoclave manufacturing technique for unidirectional composites. The proposed approach consists of three modules. The first module is a Thermochemical model to estimate temperature and the degree of cure distributions in the composite part during the cure cycle. The second and third modules are stress analysis using FE-Implicit and FE-Explicit respectively. User-material subroutine will be used to model the Viscoelastic properties of the material based on micromechanical theory. Estimated deformation of the composite part can be corrected during the autoclave process by modifying the process-tool design. The deformed composite surface is sent to CATIA for design modification of the process-tool.

Transforming Researchers into Educators: Some Reflections on the University College Dublin School of Law Syllabus Design Workshop 2010

The priority given to the development of research skills during doctrinal legal education often neglects the importance of equipping PhD students with the pedagogical skills necessary to fulfill their important educational role as academics. Thus, in many instances there is a significant gap in the requisite skill base that PhD students acquire when they complete their doctrinal education. This paper outlines a first step that has been taken to address this deficiency in postgraduate legal education in Ireland. The PhD community of the University College Dublin (UCD) School of Law convened an internal Syllabus Design Workshop in April 2010 in order to provide doctrinal students with an opportunity to design a university module and to explore the issues which arise in undertaking such an exercise. The first part of this paper outlines how the workshop was conceived and convened, and provides an account of the considerations that each student had to take into account in the design of a syllabus. From here, we address the content of the workshop and reflect upon some of the important issues which were
raised. Finally, we offer a number of recommendations in relation to the development of doctrinal students as future educators. By highlighting the importance of uniting research and teaching, it is hoped that this paper will contribute to postgraduate legal education in Ireland,and also internationally.

Quality of life in men receiving radiotherapy and neo-adjuvant androgen deprivation for prostate cancer:Results from a prospective longitudinal study

Aim. To report a study measuring the quality of life and side effects in men receiving radiotherapy and hormone ablation for prostate cancer up to 1year after treatment. Background. Prostate cancer incidence is increasing with the result that more men are living longer with the disease and the side effects of treatment. It is important to know the effects this has on their quality of life. Design. Survey. Method. Between September 2006-September 2007, all men who were about to undergo radical conformal radiotherapy ± neo-adjuvant androgen deprivation for localized prostate cancer were invited to participate in the study; 149 men were recruited. They completed the European Organization on Research and Treatment of Cancer quality of life questionnaire C-30 and Prostate Cancer module PR25 at four time-points. Results. At 4-6weeks after radiotherapy, participants experienced the biggest relative decline in global quality of life, social, physical, and role functioning and an increase in treatment side effects. At 6months postradiotherapy the majority of men experienced an improvement in their side effects. However, a minority of men were experiencing severe side effects of radiotherapy at 1year post-treatment. Single men and men who had a low quality of life prior to radiotherapy, reported a lower quality of life at 1year after treatment in comparison to married men. Conclusion. Men with prostate cancer suffer limitations due to the symptoms they experience and disruption to their quality of life. It is essential that nurses develop and deliver follow-up care which is flexible and appropriate to the individual needs of these men. © 2012 Blackwell Publishing Ltd.